RUSM03 Mini 1

After gram stain, the bacteria is found to be a gram-negative bacilli with curved and spiral rods (motile) and an aerobe- which bacteria may it be

Campylobacter sp. or Helicobacter sp. Campylobacter sp. - "Gull wing" appearance - Oxidase + - microaerophilic - grow at 42*C - motile Helicobacter sp. - Oxidase (+) - Urease (+) - Microaerophilic - Motile

NSAIDs (i.e. aspirin) inhibit

Cyclooxygenase 1 and 2

Emax is the maximum effect that can be achieved with that drug. Efficacy compares the

Emax of one drug to the Emax of another drug. If a drug has a high Emax value, it has high efficacyc

Mixed Acting Adrenergic Agonists

Ephedrine

The study of the distribution and determinants of diseases frequency in human populations

Epidemiology - Distribution - Determinants - Frequency

Intermediate filaments: cytokeratin, desmin, vimentin are markers for

Epithelial, mesenchymal and neural tumors

What are fungi?

Eukaryotic cells that posses DNA AND RNA, a defined nucleus and a cell wall (different from bacteria) - unicellular- yeasts - filamentous- molds - dimorphic- both

A pt with h/o joint pains, breathlessness and ankle swelling - exam revealed acute pulmonary edema and congestive cardiac failure- she was treated with Digoxin, Lasix and morphine but failed to show improvement - 2 weeks after admission, chest xray revealed pericardial effusion- her condition deteriorated and she died one week later - autopsy reveled cardicac changes such as fibrin strans and inflammatory infilrate in pericardium Dx?

Fibrinous Pericarditis

What are fungi?

Fungi are eukaryotic cells with complex carbohydrate cell walls and cellular membranes with ergosterol. They are non photosynthetic deriving their energy from degradation of organic compounds

What type of vaccine is Rotavirus

HUman-bovine hybrids, Attenuated (oral) - should be given in infants

Which component of the herpes virus-2 virion would most likely make an effective candidate for vaccine target?

Herpes virus-2 is enveloped - Antibodies will see membran of the herpes virus (capsid is internal - wont be visible till in the host cell ) - Lipids and glycoproteins are in the envelops - Capsid proteins prot. from most of immune response bs it is inside

Suppression

Intentionally avoiding thinking about disturbing problems, wishes, feelings or experiences

HMB-45 is a maerker for

Melanoma

Which NSAID is a salicylate derivative which is used in inflammatory bowel disease?

Mesalamine

Antibiotics that work on DNA (inhibitors of nucleic acid synthesis or function)

Metronidazole - via DNA damage

Actin is a marker for

Muscle tumors

Majority of human pathogens are

Neutrophilic mesophiles

What are the two types of binding sites that are found on many drug targets (ex. receptors)?

Orthosteric site: binding site for natural ligand Allosteric site: additional site that influences receptor activity NOTE: Allosteric inhibitor, negative allosteric modulator, uncompetitive antagonist or non-competitive antagonist all mean the SAME thing!

Pt with worsening h/o epigastric pain relieved by eating- upper GI endoscopy reveals a large gastric defect with raised rolled edges- Dx?

Peptic ulcer

Medicalization

Process by which human conditions and problems come to be defined and treated as medical conditions, and thuse become the subject of medical study, diagnosis, prevention or treatment

What is reperfusion injury?

Restoration of blood supply in an ischemic area--> exacerbation of injury (reperfusion injury) Mechanisms: - Additional influx of Ca2+ (review mech in Cell path 2 lecture) - Influx of O2--> formation of reactive oxygen species (ROS) - Inflammatory response to necrotic tissue

List the (+) ssRNA (diploid) with iDNA

Retroviridae * this is RNA and is enveloped

Indirect Acting Cholinergic Drugs- Cholinesterase Inhibitors include

Reversible & Irreversible Reversible: - Edrophonium - Physostigmine - Pyridostigmine - Neostigmine - Donepezil Irreversible (Organophosphates): - Parathion - Malathion

Neuron-specific enolase is a marker for

Small cell lung carcinoma, neuroblastoma

What are some organsims that DO NOT gram-stain

Spirochetes, Obligate intracellular, Mycobacteria, and Mycoplasma

Gram positive cocci include

Staphylococcus: grape-like clusers Streptococcus: pairs or chains Enterococcus: pairs or chains

Beta-hemolytic streptococci

Streptococcus pyogenes - bacitracin susceptible - PYR (+) (pyrolidonyl arylamidase) - Lancefield group A - Can be part of normal pharyngeal flora Streptococcus agalactiae - Bacitracin resistant - PYR (-) - Lancefield group B

What is the function of DNA polymerase III in prokaryotic replication?

Synthezies in the 5'--> 3' direction - Polymerizes nucleotides in a complex with accessory proteins at the replication fork - Readings/moving on the template in the 3'-5' direction *** Has 3'-5' exonuclease activity - allows for proofreading - can back up one step when a wrong base pair has been made

Host Antibody Response

Type of antibodies seen and change in titer over time can give you idea of: - Disease stage - Treatment success (or failure) ** IgM: usually first antibody that appears ** IgG: comes after

Responding to Strong Emotions in pts...

Understand the basis for the pts behavior and communicate honestly Communicating with pts... Suffering from psychosis: - Have poor insight into their illness- their delusions and/or hallucinations are real to them- a therapeutic alliance at this stage may be difficult. It is important to: maintain a formal relationship, not challenge or displat disbelief for the pts delusional system, not laugh at the pts strange comments or behavior, DO NOT place the pt under pressure, DO explore the extent and severity of the psychosis Aggressive pts: - Verbal confrontation in non-aggressive manner should be attempted: "I see that you are troubled. What are your concerns?" - If situation escalates and necessitates phys intervention a good statement would be: "I/we will need to help you to regain control" Major depressive pts: -Explor for suicidal ideationa nd intent: "what are your thoughts at this time" - 2 critical questions to see if pt meets partial DSM-5 criteria for major depression: "Have you lost interest in activities for the past 2 weeks, Have you been feeling sad for the past two weeks?" Non-verbal pts: - More active questioning may be required, more direct questions, use reflection if the pt fall silent, explore thoughts and feelings for poignant periods of silence - Ex: pt tells you it is useless--> you say " You said it is useless- this is reflection of content" -- this kind of pt requires empathy and support from the physician Pts with somatoform disorder: - Pts respond positively to empathy (be supportive), these pts may become dependent on you - often would not accept referral to a psychiatrist - Best thing to do: be supportive, work to improve the pts insight Pts with historionic personality disorder: - Can be flirtatious and attention seeking, Technique here is to be calm, non-flirtatious and reassuring - Techniques: do not respond, explore for what may be behing the behavior, establish boundaries by setting limits Pts with dependent personality disorder: - If pts requests you make decision good communication technique would be: "I would consider these options best for you"- ranking them in order of priority Pts with borderline personality disorder: - pts have difficulty in delaying gratification- they are easily frustrated and can be manipulative- set limes, remain professional, boundaried stands - define acceptable and non-acceptable behaviors at the beginning of your clinical work with pt Pts with obsessive compulsive personality disorder: - Pts can be critical, evasic, and suspricious - Provide careful explanations, remain non-defensive, develop "frustration tolerance", coping with pts demands Pts with anti-social personality disorder: - Pts may be manipulative, impulsive, and dangerous- be respectful, but vigilant- set and maintian boundaries- confrontation may be necessary to point out to the pt that his or her behavior has reach point of being unacceptable Pts with substance use or addicitve disorder: - Pt may have lack of insight, utilizing denial/other defence mechanisms (ex. rationalization, projection, minimization, humor, etc) - Appropriate confrontation may be used to address defensive stance - Confront only when the clinical history, physical exam and lab tests point to the likely diagnosis of substance use disorder

What type of vaccine is human papillomavirus

VLP= virus-like particle, adjuv. - should be given to 9-26 yo (F) and 9-21 for (M)

What are the 2 hosts of malaria?

Vertebrate (humans): intermediate host Mosquito: definitive host Life cycle 1. sporozoite 2. merozoite 3. schizont 4. gametocyte

"Would I be happy for the pt to read these notes?"

When documenting medical records - stay neutral and professional - avoid hostile and derogatory statements - pts have right to access their records

Childhood

ages 1-12yrs - prefecting gross and fine motor skills and acquiring new ones --> increasing mobility and independence - lang. acquisiton - increased ability to think and reason logically - socialization outside fam circle Phases 1. Toddler (up to 3yo) - 15 months: wants to be just like big sister, walks confidently to the blocks and imitates making a 2 block tower (little sissy) - 18 months: 4 block toward with catapult that has cup on end; so shoves note in with spoon, and throws it at Rapunzel, hittiner her in face - 2-21/2="terrible twos": two commands to twin boys run up stairs, walk up 25 stairs, scraming, not helping, in the playroom this morning "daddy did it" (bad twins) - 3 yrs: jumps into 3 piece suit, says full name, jumps only tricycle "you.me.I" is his pick up line 2. Pre-school (up to 6yo) -4 yrs: story time, runs up stairs, hops on one foot to undress, read story together (bedtime storry baby) - 5 yrs: ties shows, finds out wizard was not rlly wizard, says bye to Tin Man and then skips down Yellow brick road back to kansas (Oz bby) - 6 yrs: lang fluent and clear, symbolic thouhg, egocentric (world revolves around me), imaginary friends, co-operative and "lets pretend" play, expresses emotions [[0-5 yo - the child on the 1st floor of her house sits up, crawls, cruises then 1. walks to stairs 1.5. throws objects up stairs 2. climbs up stairs and runs to his trike 3. rides a trike upstairs, jumps off 4. runs down the stairs, hops off the stairs and 5. skips away]] 4. School age (up to 12yo) - Pre-puberty - able to express ideas - logical reasoning - conservation: changing the form/shape of a substance or object does not change its amount, overall volume or mass - Formal learning begins - Social & sexual development: sstrong peer interaction- best friends, gender identification, empathy and concern, latency period of sexual development - gender identity= childs perception of own gender (toddler stage 2-3yrs) - gender identification: recognizing other childrens gender and forming socialization preferences based on this recognition - most : binary gender identity: boy or girl

Drug allergy

an immunologically mediated, adverse drug effect that reoccurs when pt is re-exposed to the drug (only after a previous sensitizing contact with same drug or which drug closely related in chemical structure which is called cross sensitization) * Second triggering contact with same drug will provoke production of antigen-antibody complex (or activation of the sensitized T cells) *Seriousness of allergic rx is NOT dose-dependent - In order for a drug to induce an allergic response it must have immunogenic properities i.e. it must behave as an antigen (only molecules with a MW > 6000 can be immunogenic A Drug may cause an allergic rx only if: - MW > 6000 or - It can function as hapten, that is, it is capable of binding covalently to a macromolexule, for ex a protein to forma a larger product that has immunogenic properties Gell and Coombs classification of allergic reactions (mechanism by which antigen evokes the immunologic response): 1. Type I (immediate reactions) - 1st exposure --> IgE - 2nd exposure--> antigen-antibody reaction on the surface of sensitized cells causes the release of potent vasoactive and inflammatory mediators (histamine, heparin, kinins, leukotriens, platelet activating factor, slow reacting substance) either preformed or newly generated from membrnae lipids ---> trigger allergic inflamm reponse Ex: Anaphylaxis 2. Type II (antibody-dependent cytotoxicity) - Drug binds to surface component of cell, ie RBC causing it to appear foreign --> IgG or IgM that can react with cell-bound drug (autoimmune reaction) --> may tigger complement system or permit attack by mononuclear killer cells --> death of target cell either way Ex: Hemolytic anemia, Thrombocytopenia, Severe neutropenia and agranulocytosis ** review drugs that cause these in Adverse effects of drugs handout 3. Type III (immune complex-mediated reaction): - IgG or IgM formed against soluble antigens - if antigen in excess of antibody --> immune complex may remain soluble in blood and conitnue to circulate --> deposits on walls of blood vessels, at basement membranes, causing complement activation and local inflammation - Although IgE may play some role its mostly IgG or IgM Ex: serum sickness, systemic lupus erythematous, some forms of hepatitis, nephritis, arthtitic, vasculitis 4. Type IV (delayed or cell-mediated reaction) - NOT mediate by antibodies - Antigen sensitizes T lymphocytes which produce T cell receptors appropraite for reacting with the antigen - On second exposure T lymphocyte recog antigen and release lymphokines which produce local edema and inflammation -- called delayed bc hrs or days elapse for reaction to occur after administration of an eliciting dose of antigen to a sensitized suject - Skin is chief site of allergic response ** Contact dermatitis most common - other types include eczema, erythema multiforms, steven johnson syndrome

Bactericidal vs. Bacteriostatic

bactericidal kills the cell, bacteriostatic stops replication

Increased HR can only be due to

beta1 receptor

Dissociation

deal with emotional conflict or internal or external stressors through a temporary but drastic change in personality, memory, consciousness, or motor behavior

Antiseptics can be used for

disinfecting live tissue - alcohols - chlorhexidine - iodophors Antiseptics CANNOT kill spores - Some antispetics (ex. Betadine) can kill mycobacteria, but most cannot

Intelleclulization

excessive use of abstract thinking or the making of generalizations to control or minimize disturbing feelings

Repression

expelling disturbing wishes, thoughts, or experinces from conscious awareness- the feeling component may remain conscious, detached from its associated ideas

If x-axis is linear, then both curves are

hyperbolic - If x-axis is logarithmic, then both curves are sigmoidal

There are __________ muscarinic receptors on (endothelium) blood vessels

non-innervated

Host to Host virus transmission occurs via

- Direct contact (ex. Human herpesvirus 1) - Injection of contaminated fluids or blood (ex. Mosquito bite, injectable drug) (ex. Dengue) - Organ transplant (ex. Human cytomegalovirus**) - Airbone (ex. Influenza) - Fecal-oral (ex. Norovirus)

Gram negative cocci - Neisseriae

- N. gonorrheae - N. meningitidis

Describe the morphology of reperfusion injury

- mitochondrial swelling - rupture of cristae - calcium deposits

Sweating produced by alpha1 receptor vs. muscarinic

Alpha 1 controls piloerection and apocrine (stress) sweating Muscarinic receptors control thermoregulatory sweating (symp cholinergic)

Clonidine has receptor affinity for

Alpha2

Taeniasis

Beef tapeworm- T. saginata Pork tapeworm- T. solium Intestinal disease (from beef, pork)--> leads to "Taeniasis" Tissue disease (from eggs of T solium) --> leads to "Cysticercosis" Diagnosis: Eggs/proglottidis in human feces

Albuterol/Terbutaline has receptor affinity for

Beta2

Mirabegron has receptor affinity for

Beta3

Which NSAID is - available OTC - a topical preparation and on ophthalmic solution are also available - more GI toxicity than ibuprofen but less than aspirin - long half life- apprx 14 hrs

Naproxen

Which causes heartburn naproxen or celecoxib?

Naproxen can cause heartburn - Naproxen is nonselective COX inhibitor - Celecoxib is a COX2 selective inhibitor

Bacterial Chromosome (aka Nucleoid)

- Circular, double-stranded DNA; exons only - Coiled/Supercoiled/anchored by proteins - 0.5-10Mb in size Ex: - Mycoplasma genitalium - 580kb - Staphylococcus aureus- 2.8Mb - Mycobacterium tuberculosis- 4.4Mb - Escherichia coli- 4.6Mb - Pseudomonas aeruginosa- 6.3Mb

What are some examples of physiologic atrophy?

- Embryonic structures (notochord, thyroglossal duct) during fetal development - Myometrium after delivery - Endometrium and breast after menopause

Ca in Situ

Carcinoma in situ is the MOST SEVERE form of dysplasia - dysplastic cells occupy the whole thickness of the epithelium - cytological features of malignancy - cells do NOT spread beyond the basement membrane - potentially REVERSIBLE*

What are some causes and mechanisms of cell injury and necrosis?

Causes: - Hypoxia and ischemia - Microorganisms - Immunologic reactions - Chemical agents and drugs - Physical agents (heat, cold, irradiation, and trauma) - Genetic derangements - Nutritional imbalances Mechanisms: - ATP depletion - Mitochondrial damage - Influx of calcium - Generation of free radicals - Defects in membrane permeability

Cellular Atypia

Cellular pleomorphism (cells vary in size and shape) Nuclear changes - nuclear pleomorphism (nuclei vary in size and shape) - dense and irregular nuclear outline - nuclear hyperchromicity (increased DNA content) - multinucleation - nucleolar pleomorphism (nucleoli vary in size and shape) Increased (up to 1:1) nucleo/cytoplasmic ration (nml ration ~1.5) *** Cellular Atypia is seen in MALIGNANT neoplasms only

Which substances is known to enhance engulfment/phagocytosis?

Complement C3b (it facilitates phagocytosis)

Potency and Efficacy

High potency= lowest concentration needed to achieve a full effect (smalles EC50) Lowest potency= need higher concentration of drug to produce a certain effect (large EC50) Efficacy - Full agonist can reach 100% max effect - Partial agonist have efficacy but NOT same as full agonist Full agonist= affinity and maximum efficacy Partial agonist= affinity and partial efficacy (cant produce full response) Antagonist= affinity but NO efficacy Inverse agonist= affinity but negative efficacy (decreases activity)

What type of vaccine should be given for Influenza

(1) Inactivated, adjuv. (2) Attenuated (nasal spray) Should be given to (1) children and adults, healthcare workers, and the elderly (2) 2-50yo

Nemathelminthes (Round worms)

Intestinal nematodes: 1. Ascaris lumbricoides (round) 2. Strongyloides stercoralis (thread) 3. Ancylostoma duodenale (hook) 4. Enterobius vermicularis (pin) 5. Trichuris trichiura (whip) 6. Trichinella spiralis (pork) 7. Necator americanus (hook)

Twitching Motility

Is pilus-mediated and allows bacteria to move along mucosal surfaces - Twitching motility: form of solid surface translocation - Flagella independent - Occurs in a wide range of bacteria (pathogenic neisseria, Moraxella, Pseudomonas) ** Twitching motility occurs via retraction and extension of the pilus (grappling hook model) Ex: Shower curtain schummy? Bacteria using twitching motility to move across shower door and continues to grow as doing it

Rationalism

Mathematicl certainty is epitome of knowledge Path to sure knowledge is through reasons objective gaze and reason is the primary source of knowledge Ideal scientist or scholar is: - disengaged and rational - unencumbered by preconceptions - free from mere opion

Differentiate between NSAID and Acetaminophen therapeutic uses

NSAIDs: - inflammation - fever - pain - cardiovascular protection (aspirin) - topical use to relieve pain (diclofenac, ketorolac) Acetaminophen: - fever - pain - useful in children or patients with GI complaints/risks - not useful for persons with inflammation/inflammatory conditions

Hos is a pathogen "actively" introduced to the host?

Natural: - host experiences natural infection and mounts immune response Artificial: - recipients immune response is prompted to respond as if the body were experiencing infection with the pathogen

Necroptosis vs. Pyroptosis

Necroptosis - caused by activation of extrinsic pathway of apoptosis (TNF, Fas) - details of mechanism unkown, receptor-associated kinases (RIP1 and RIP3) are involved. No activation of caspases - Morphology= necrosis Pyroptosis: - caused by presence of intracellular microorganisms - due to activation of caspases 1 and 11 - Morphology= necrosis

Lab diagnosis for HHV5 of HCMV (human cytomegalovirus)

Nucleic acid testing is the method of choice**** Histopathology: owl's eye inclusions (need biopsy- somewhat invasive) Serology

Reversible--> Irreversible Injury/Cell death table

Reversible cell injury the cell function declines but then turns back to normal In irreversible cell injury: Cell function declines leading to - Biochemical alterations --> Cell death - Ultrastructual changes - Light microscopic changes - Gross morphologic changes

What is S.O.L.E.R?

S- Face the pt squarely which shows involvement O- Adopt an open posture. Crossing arms or legs may not communicate openness or availability L- Lean towards other person- moving forward or backward can communicate lessened involvement E- Maintain eye contact- this is normal behavior for two individuals who are involved in conversations. Dont stare! R- Try to be relaxed. This means avoiding nervous habits

Congenital or acquired immunodeficiency can affect

T- cell immunity leading to a major type of cancer: lymphoma

T or F: The more similar a vaccine is to the disease-causing form of the organism, the better the immune response to the vaccine

True!

Transplant recepitents, pts with AIDS and genitcally immuno-deficient ppl are at high risk for lymphorpoliferative disorders initiated by EBV--- these disordesr may appear as polyclonal and monoclonal B-cell lymphomas---> such ppt are also at high risk for

a productive EBV infection in form of hairy oral leukoplakia

Norepinephrine receptor affinities

alpha1=alpha2 Beta1

Antymycobacterial drugs

(Aminoglycosides) (Fluoroquinolones) Rifamycins (rifampin) Others (isoniazid, pyrazinamide, ethambutol)

Adaptation vs. Cell injury

(Physiologic) Adaptation: influence of a stimulus--> cellular response within the homeostatic limits - Ex: breast in pregnancy and lactation Pathologic Adaptation: influence of a potentially harmful stimulus--> cellular response beyond the homeostatic limits, but changes do not reach a level of cell injury - Ex: denervation atrophy of skeletal muscles Cell injury: A sequence of events that occur, if the limits of adaptive capability are exceeded, or no adaptive response is possible

Beta1 functions

- Increases force and rate of contraction of the heart - Increases renin release in the kidney; juxtaglomerular cells

alpha1 receptor

- Most vascular smooth muscle --> contraction - Pupillary dilator muscle --> contraction (mydriasis) - Prostate; urinary sphincter--> contraction

What are the 3 major types of active immunizations

1. Inactivated vaccines 2. Live attenuated vaccines 3. DNA vaccines

What are some factors that can affect the outcome of a preg?

1. Psychological factors: - maternal stress (increases adrenaline and cortisol--> decreased placental blood flow--> fetal hypoxia) - may also be a central neurologic component causing abnormal placental blood flow 2. Socioeconomic circumstances: - poverty and domestiv violence may result in preterm deliveries and small for gestational age (SGA) babies 3. Nutrition: - severe malnutrition in mom--> intrauterine growth restriction (IUGR) - vit. deficiences in vegan moms - administer folic acid (prevent neural tube defects, vitamin supplements (careful with overdosing vit A-teratogenic) 4. Metabolic - Diabetes (macrosomia, congenital heart disease) - hyperthyroidism - phenylketonuria (PKU) 5. Maternal disease - preg in moms with HTN, renal fialure, heart failure, sickle cell disease may resut in premature births or IUGR 6. Congenital infections - TORCH: toxoplasmosis, other (T. pallidum, varicella zoster, parvovirus B19, HIV, enterovirus, B.burgodorferi, rubella, cytomegalovirus, herpes simplex --- can produce placental barrier and produce cong. infections in fetus - there is poor motor and cog development in some of these children Ex: congenital rubella--> visual defects, deafness and developmental delay 7. Maternal age: - older mothers: increased risk of pre-eclampsia with premature delivery or trisomy 21 8. Pharmacological facors Drug abuse: - fetal alcohol syndrome - drug withdrawal - tobacco: premature births, IUGR Medications: - some contraindicated in preg. Teratogenic drugs: - acne medications (retinoids) - anti-convulsants - certain antibiotics 9. Stage of fetal maturation - Effect of teratogens depends on gestational age of fetus at which they impacted pred Ex: - Rubella in first semester- when critical organs like brain, sensory organs and heart developing - Tetracyclin: tooth abnormalities in 2 and 3 trimester, tooth development occurs

Deal with emotional conflict or internal or external stressors by transferring a feeling about, or a response to, one onject onto another (usually less threatening) substitute object

Displacement

How do F' plasmids form?

By incorrect excision of integrated F plasmid (piece of host chromosomal DNA attached to plasmid) - Can now horizontally transfer bacterial genes from host to host

BCL-2 is a marker for

Follicular lymphoma

What stains can be used to identify Hemosiderin?

H+E stain and Perl's/Prussian Blue which will stain iron in blue (hemochromatosis)

How is FISH used to diagnosis cancers?

It can help in visualizing if two chromosomes are fuse Ex: In CML t(9;22) these chromsomes are fused, whereas normally they would be seen separate

Amphetamines

MOA: - Stiimulation of release of monoamines (NE, dopamine, and serotonin) from storage sites, both peripherally and in the CNA (the main mechanism) - Blockade of catecholamine reuptake can also occur Pharmacodynamics: - Peripheral effects are very close to those of NE - Central effects include euphoria and increased ability to concentrate

List the intestinal flagellate

Mainly Giardia in the US - Giardia lamblia - Giardia intestinalis - Giardia duodenalis - Giardiasis Mode: ingestion of cysts (outdoor water; spring) Site: intestine only Diagnosis: cysts in feces

Traumatic Fat Necrosis

Organ affected: female breast Mechanism: mechanical trauma--> cell injury and necrosis of adipose tissue --> inflammation --> calcification and scarring Significance: mimics breast carcinoma

Nonselective alpha-antagonists (alpha1 and alpha2)

Phentolamine Phenoxybenzamine

Primary vs. Secondary immune response

Presence of high levels of IgM antibody is indicative of a primary response, i.e. a current infection High levels of IgG antibody would indicated a secondary response i.e. a past infection or reinfection

falsely attributing to another his or her own unacceptable feelings, impulses, or thoughts

Projection

Goals of vaccination

Promote the development of immunity: (vaccinate aka immunize) - to protect the individual from the disease or severe sequelae associated with the disease - to protects others who cannot be immunized (ex. infants, immunocompromised)

Describe the viral capsid/nucleocapsid

Protective shell of the virion Composition: Built from many copies of one or several self-arranging proteins Functions: - Packaging and protection of genomic nucleic acid cardo (all viruses) and essential/accessory proteins (depending on viruses) - Adhesion (naked viruses only)

Differentiate between quantal vs. graded curve

Quantal= all-or-none - ex. yes or no? (did effect happen) - ex. did event happen? - how many participants experienced the event? ED50: dose at which 50% of participants experienced the event Graded: all, none, and everything in between - ex. how big of a response was observed? - ex. concentration-effect curve

Regression (R) *** dont confuse with r=correlation

R is used for hypothesis testing and making predications Independent variables: interval or ratio Dependent variables: interval or ratio

How can the Retinoic Acid Receptor (RARa) lead to cancer?

RARa: retinoic acid receptor alpha, a factor stimulating cell differentiation t(15;17)--> formation of a PML-RARA hybrid with low affinity to retinoic acid, if given in a physiologic dose--. Acute promyelocytic leukemia (APML) Treatment of APML: all-trans retinoic acid, given in a therapeutic dose, binds RARalpha and activates cell differentiation

___ to isolate colonies

Subculture - to purely isolate and make sure you are only looking at one organism

What vaccine should you use for Clostridium tetani (tetanus) (TDaP)

Toxoid Vaccine Type - should be received by: children, adolescents, and adults and pregnant women

Blastoconidia is a spore formed by

Yeasts like Candida albicans or other dimorphic fungi in their yeast stage - Blastoconidia= blastospores= buds (asexual spores)

Bordetella Pertussis vaccine targets

adhesins - Adherence of Bordetella Pertussis to ciliated epithelial cells requires fimbriae, FHA (filamentous hemagglutinin), and pertactin. The acellular pertussis vaccine contains FHA and pertactin --> vaccine makes antibodies against these foreign proteins --> so when have organism inside body immune system primed and ready to go

Epinephrine has BOTH

alpha and beta effects It can.... - increases systolic BP (beta1 direct effect) - increase diastolic BP (alpha1-vasoconstriction) - increase cardiac output (beta1) - increase HR (beta1)

Epinephrine has equal receptor affinities for

beta1=beta2 alpha1=alpha2

Odds ratio is calculated in

case-control studies by calculating the odds of exposure among the disease cases to that among the controls

Anthroconidia is a spore formed by

fragmentation of hyphae - this may occur in tissue (like skin) or environment - They are released by a process of breakage at the "joints"

Coombs test

is used to detect the presence of antibody against blood cells, usually erythrocytes Direct Coombs test: detects antibody bound to erythrocytes ** RBCs will agglutinate- antihuman antibodies form links between RBCs by binding to the human antibodies on the RBCs Indirect Coombs test: detects unbound antibody in serum - the unbound antibody could bind to transfused erythrocytes bearing the specific antigen ** Agglutination of RBCs occur, bc humans Ig's are attached to RBCs Positive Coombs test: - means that antibody is present and immune hemolysis may occur- this may be seen in autoimmune or drug induced hemolytic anemia, hemolytic transfusion reactions, Rh sensitization, certain infections and autoimmune diseases

Respriatory difficulties in poisoning by antimuscarinic drugs are due to blockade of

muscarinic receptors in the brain NOT the lungs ** Central respiratory depresioon-- brain not telling you to breathe--> going into coma state

Fever occurs when the

set-point of the anterior hypothalamic thermoregulatory center is elevated - This can be caused by PGE2 synthesis, which is stimulated when endogenous fever-producing agents (pyrogens), such as cytokines, are released from WBCs that are activated by infection, hypersensitivity, malignancy, or inflammation NSAIDs lower body temp in pts with fever by inhibiting PGE2 synthesis and release, resetting the "thermostat" back toward normal NSAIDs reduce fever, but do NOT reduce increased body temp due to exercise or ambient heat

Isolation of Affect

splitting off of the emotional components from a thought Ex. med student dissects a cadaver without being distrubed by thoughs of death - may be temporary (affect postponement) Ex: bank teller appears calm and cool while frustrating robbery but afterword is tearful and termulous

Reaction formation

sustituting behavior, thoughts, or feelings that are diametrically opposed to his or her own unacceptable thoughts or feelings (this usually occurs in conjunction with their repression)

Muscarinic receptos on sweat glands; however innervation is

sympathetic-cholinergic

The sublingual and buccal route of drug administration are mainly used for

systemic effects - Sublingual route involves placement of drug under the tongue - Buccal route involves placement of drug between the cheek and gum ** Both have several advantages: ease of administration, rapid absorption, bypass the harsh GI environment and avoidance of the first-pass effect

Cestodes are

tapeworms

In indirect fluorescent antibody test

the primary antibody is not labeled - The antibody-antigen conjugate is detected using labeled anti-antibody, i.e. a tagged or labeled secondary antibody

Interpretic understanding

this reductionism is unsuited to understanding human life - imagination - intuition - memory - feeling ** Described "empathic insight", "intuitive sympathy", as ways of knowing basic to all humane studies

T or F: Hydrophilic drugs are easily eliminated

true!

Describe release of a virus

Cell lysis: - usually naked, some enveloped that get membrane from organelle - usually causes important cytopathic effects Budding: - usually enveloped viruses, especially if envelope from cytoplasmic membrane - usually cause minimal/no cytopathic effects - host cell can continue to produce viral particles Exocytosis: - some enveloped viruses Direct transfer to another cell: - virus particle, nucleocapsid, or genome alone - cell-cell bridges, cell-cell fusion, vertical

Describe the Effect of alpha-antagonists on Adrenergic drugs (epinephrine, norepinephrine, phenyephrine)

Epinephrine: activates alpha1 + beta1 + beta2 - adding an alpha1 antagonist --> you get beta1 + beta2 activation (decreased diastolic BP, systolic unchanged, decreased BP, increased HR) Norepinephrine: activates alpha1 + beta1 - adding an alpha1 antagonist--> you get only beta1 (increased HR) Phenylephrine: activates alpha1- adding alpha1 antagonist you get no receptor activation (non) Think about: - What is the effect of the adrenergic drugs on BP (systolic and diastolic) before and after the addition of an alpha-antagonist? What about after a beta-blocker?

Describe the Lytic Cycle (i.e. In Human Herpesvirus 1 (HHV-1) aka Herpes simplex virus 1 or HSV-1)

Herpesvirus productive infection usually leads to cell destruction (lysis) - HHV-1 and HHV-2 have lytic replication in EPITHELIAL cells - 1 replication cycle ~ 18-20 hrs for HHV-1 and HHV-2 There are at least 84 viral proteins expressed, with many ORFs to be characterized (>90 uniqque transcriptional units) - Many viral proteins have to complex with host proteins to function - Several non-translated RNAs expressed Steps: 1. Binding - Herpesvirus glycoproteins B and C (gB & gC) with host cell glycosaminoglycans (including heparan sulfates) which hold to the virion close to the membrane - gD starts the diffusion process 2. Fusion & Entry At plasma membrane or following endocytosis, depending on virus - Glycoproteins D, H/L and the fusion protein gB (gD, gH/gL & gB) interact with host cell nectins (nectin 1 or 2), herpesvirus entry mediator (HVEM), or 3-O-sulfated heparan sulfate (3-OS HS) or another receptor to penetrate the cytosol ** gB starts binding then comes back into the picture and binds glycosamine to bind cell--> gC makes binding tighter--> gD docks with receptor and induces conformational change--> gH/gL recruited to do another conf. change--> recruit gB again --> gB allows fusion pore to be created by which nucleocapsid enters cell - release receptor from gD--> pore allows nucleocapside to enter cell [Tegument Roles: Outer Tegument: - Antiviral defense inhibition (VHS or virion host shut off protein, a product of the UL41 gene) - Host protein synthesis inhibition (VHS) Inner tegument: - Carried to nuclear pore with nucleocapsid - Involved with injection of viral DNA into nucleus - Involved in the transcriptional activation of alpha genes or immediate-early genes (VP16, a product of the UL48 gene) Tegument proteins do: Host RNA degradation, Viral gene expression, Host evasion, Host cell activation, Stimulation of viral gene expression and modulation of host cell] 3. Translocation - Of nucleocapsid and inner tegument to nuclear pore complex by way of microtuble active transport - dynein motors 4. Docking and injection - Capsid docking: one or more viral proteins (presumably UL25 interacts with host nuclear factor importin beta and several nuclear pore complex proteins (Nup358/RanBP2 & Nup214/CAN) - Injection of linear dsDNA through the nuclear pore: dsDNA injection is ATP and pressure (repulsive electrostatic charged by negatively charged phosphates) dependent)--> DNA circularizes 5. Replication 6. Assembly (produces cytopathic effects) 7. Encapsidation 8. Egress - Envelopment- Renvelopment (MOST common) - Membranes may be derived from plasma membrane or from nuclear membrane--> many different virions who acquired envelope from diff compartments of the cell--> but MOST envelope comes from golgi - Virion is released by exocytosis (cell to cell transmission can yield syncytia-- role of gB fusion protein*** ) Can yield: - Formation of syncytia: Giant multinucleated cells and lysis of infected cell - Formation of nuclear includion bodies with chromatin margination: Cowdry type A inclusion bodies and owl's eye inclusions

DNA viral genomes can be

- Double-stranded (dsDNA, +/- DNA) - Single-stranded (ssDNA, + or - or both) - Partially double-stranded (gapped, iRNA)

What are the genera of the major US dimorphic pathogens?

- Histoplasma - Blastomyces - Coccidioides - Sporothrix

What are some anatomic sites with normal microbiota?

- Mouth, nares, upper resp. tract - GI - Skin - Female genital tract - Urethra

List the (-) ssRNA viruses

- Paramyxoviridae - Deltaviridae *these are RNA and both enveloped

Staphylococcus aureus is seen in

- skin infections - osteomyelitis - endocarditis - food poisoning - septicemia - necortizing pneumonia - toxic shock syndrome Can cause: - Folliculitis - Carbuncles - Furuncles - Staphylococcal Scalded skin syndrome - Superficial impetigo

Mycobacteria DO NOT gram stain- describe them

- small rods, no outer membrane - cell wall contains waxy mycolic acids - acid-fast staining - resistant to drying, chemical agents, germicides, gram stain - aerobes - slow growing

pH=pKa

50% availability of both species

Exploratory Technique

A powerful technique for understanding dynamics behind unusual or unexpected behavior Exploration is a priority ex.: - Pt presents with depressed feelings or expresses hopeless feelings --> Explore for suicidal intent - Pt expresses hostile emotins --> Explore intent to harm - Pt expresses fearful emotions --> Validate and explore the intent to withdraw

Predisposition to Cancer

A set of clinical and experimental circumstances associated with an increase risk of cancer development Types of predisposing conditions: Acquired: - chronic inflammation - precursor lesions - immunodeficiency Genetic: - inherited cancer syndromes

Trichomonas vaginalis

A urogenital flagellate "Trichomoniasis" - World wide occurence Mode: direct sexual contact Site: vagina in females, urethra in males Diagnosis: *WET MOUNT of vaginal smear to show RAPIDLY MOTILE trophozoites **NO cysts are formed

Binding of a drug to a drug target leads to a drug response, such as..

Activation/Inhibition of target - stimulate (or prevent stimulation of) a signal transduction pathway - enhance (or prevent) action of endogenous ligand (ex. neurotransmitter or hormone) - increase (or decrease) activity of an enzyme - increase (or decrease) gene transcription - increase (or decrease) membrane potential

Phenylephrine has receptor affinity for

Alpha1

Recurrence of tumors

An appearance of the tumor at the previous site after treatment (surgical, chemical, or radiation) Recurrence is a feature of malignant tumors - some benign tumor (without capsule) can also recur, especially, lymphagioma and desmoid

Balantidum coli

An intestinal ciliate - common parasite of animals (pig) "Balantidiasis" Mode: ingestion of cysts Site: intestine Diagnosis: cysts in feces ** Hardly seen in humans but mainly in farmers or veterinarians

What are the 4 categories of Antimicrobials?

Antibacterial, Antiviral, Antifungal, Antiparasite - may work against one or multiple microbes - subcategories in each categorized by biochemical properties Antimicrobial target essential components of biochemical reactions in the microbes, interfere with these physiological pathways and inhibit or kill the microorganisms

Which protozoa is easily confused with malaria?

Babesiosis - Babesia microti - Babesia divergens Vector: **Tick (Ixodes) - this is same vector of Lyme disease

Benign vs. Malignant Tumors

Benign - Expansize local growth - Absent metastases - Slow growth rate - few # of mitoses - differentiated - tissue atypia present - cellular atypia absent - rare recurrence - insignificant effects on host Malignant - Invasice local growth - Metastases present - Rapid growth rate - Many # of Mitoses - Less differentiated - Tissue atypia present - Cellular atypia present - Recurrence frequent - Significant effects on the host

Classification of Tumors based on Lack of Differentiation

Benign tumors--> ALWAYS DIFFERENTIATED, but not completely as normal tissues Malignant tumors vary in degree of differentiation - Well-differntiated i.e. cancy may be well-differentiated - Moderately differentiated - Poorly-differentiated - Anaplastic: TOTALLY UNDIFFERENTIATED ** Anaplasia (literally- for form backward): complete lack of differentiation, both structural and functional; anaplasia is a hallmark of highly malignant tumors

Bile esculin agar (BEA)

Bile salts inhibit the growth of gram-positive organisms and most streptococci except Group D streptococcus and enterococcus. - Esculin can be hydrolyzed by enterococcus and group D streptococcus to esculitin, which interacts with iron to form a black precipitate of ferrous sulfate. Can be plate or tube

A 40 yo woman was treated with an alpha1-agonist. What is the predicted effect on the HR after drug was administered?

Bradycardia NOTE: there are NO alpha1 receptors on the heart--> alpha1 on BV which will increase Ca2+ SM--> vasoconstriction throughout body --> increased BP --> HR will decrease (bradycardia) in order to return to homeostasis

What is the bacteriophage host range determined by?

By adhesins (ex. on tail fibre) and host cell receptors (not any virus can infect any bacterial cells- certain tropisms (resp, GI, virus etc. this is same for bacteria) Broad host range: - relatively rare, but probably very important in DNA transfer between genera Narrow host range: - MUCH MORE common, can only infect 1 species, or even only one or a few strains

Capsular Polysaccharide Conjugate Vaccines

Capsule polysaccharide conjugated to a protein (ex. diphtheria toxoid) binds to surface antipolysaccharide IgM on the B cell--> the complex is internalized, processed, and then a peptide is presented on MHCII to CD4 T cells --> the T cells become activated, produce cytokines, and promote immunoglobulin class switiching for the polysaccharide-specific B cell--> the B cell can become activated, make IgG, and memory cells will develop ** Capsular polysaccharides are poor immunogens, do NOT elicit T-cell help, and only elicit IgM without memory

After a gram strain, you find that the bacteria is a gram-positive bacilli, non endospore-forming and aerobic- what types of bacteria can it be

Corynebacterium or Nocardia Corynebacterium: - part of normal skin, vaginal, pharyngeal flora - toxigenic strains cause disease - can be "club-shaped" or can take appearance of "chinese letters" - brown/black colonies on tellurite agar - on Loeffler agar, colonies white, cells have polar "metachromatic granules" with special stains Nocardia: - filamentous, branching - found in soil & water - partially acid-fast

Defective vs. Increased apoptosis

Defective apoptosis--> increased cell survival - TP53 mutation--> cancer (breast, prostate, ovarian, and many others) - No elimination of autoreactive lymphocytes --> autoimmune disorders Increased apoptosis--> excessive cell death - cell death in viral infection, ex. viral hepatitis - neurogenerative diseases, ex. Alzheimer, Huntington, and Parkinson disease

Fluorescence microscopy: Immunofluorescence

Fluorescent molecule conjugated to antibody - Specific Ab= high specificity - Direct Fluorescent Antibody (DFA) - Indirect Fluorescent Antibody (IFA)- is more frequent

Gram Positive vs. Gram negative envelope structures

Gram Positive: - Plasma membrane - Periplasmic space - Lipoteichoic acids traversing wall and anchored in membrane - Peptidoglycan Gram Negative: - Plasma membrane - Periplasmic space - Peptidoglycan - Outer membrane - Lipopolysaccharid and protein

PNS effect in the heart is mediated by what receptor?

M2 - decreases HR in SA node - decreases contractility in the Atria - decreases conduction velocity in the AV node - Slight decrease in contractility in the ventricle

What are two types of genome packaging for viruses?

Packaging= insertion of NA into capsid/nucleocapsid - Sequential packaging= icosahedral viruses - Concerted/coordinated packaging= filamentous, some icosahedral viruses **these molecular interactions drive assembly

Cell Senescence

Telomere shortening --> p53 activation--> ... CDKN2A (p16 and p14) activation--> cell cycle inhibition

How do we acquire fungal infection?

Via - Normal surface flora acquired during birth or later by contact with people, floors, etc. - Inhalation of airborne organism for pneumonias - Traumatic implantation generally of soil or plant fungi Ex: Mucormycosis (from high winds that bring sand into skin)

What is a classical description for pneumococcal pneumonia?

cough, high-grade fever, chills, rights and general malaise - sudden onset of sxs - h/o producing rusty sputum and chest pain on inspiration PE: - temp: 39.4*C - pulse: 90/min (tachycardia- normal is around 70/min) - RR: 30/min (N=14/min) - tachypnea chest exam: dull percussion in right upper zone of lung, decreased, air entry and bronchial breathing: pleural rub present Labs show increased WBC levels with 95% neutrophils Chest x-ray: consolidation in right upper lobe Sputum cultur: streptococcus pneumoniae On histo: - all the alveolar air spaces are distended by a cellular infiltrate - the alveolar septae are widened and also show infiltration by neutrophils

In a pt with an acute MI- what change in the myocardium is responsible for the elevated creatine kinase levels in the pt?

cytomembrane injury --> increased enzyme levels in pts

Toxins INHIBIT host cells via distinct mechanisms. Some are

cytotoxic (kill host cells) and some are cytotonic (alter cellular pathways but DONT kill cells). ** The targeted cells are often professional phagocytes (phagocytes= first cell that will try to get rid of microorganism so this is the one we go after)

Fixation

deal with emotional conflict or internal or external stressors by partially remaining at a more childish level of development

What are the requirements for nucleic acid production in each type of virus?

dsDNA: - cellular or viral DNA-dep DNA pol (replication) - cellular DNA-dep RNApol (transcription) Gapped DNA: - cellular DNA repair system - cellular DNA-dep RNApol - viral RNA-dep DNApol (RT) (+/-) ssDNA: - cellular DNA-dep DNA pol (replication) - cellular DNA-dep RNApol (transcription) (+) ssRNA: - viral RNA-dep RNA pol (-) ssRNA/dsRNA: - viral RNA-dep RNA pol (**) *** (-)ssRNA must make (+) sense first so that acts as mRNA and proteins can be made (+) ssRNA with iDNA: - viral RNA-dep DNApol (RT, **) - cellular DNA-dep RNApol Ex: Which enzyme would replicate reoviridae viral genome? - Reoviridae is an RNA virus (it needs RNA-dep-RNA pol) NOTE: - Host cell able to produce DNA and RNA- is this always happening? - XXX-dependent YYY-polymerase: X=Template; Y= what is being produced - Viral versions are encoded on viral genome - MAY need to carry the polymerase protein in the virion (**)

When compared to ibuprofen, celecoxib has a lower risk of GI adverse effects, but it can cause an increased risk of

heart attacks ** Blockbox warning for COX2- inhibit prostacyclin but not TXA

Epstein-Barr Virus (EBV) causes

heterophile antibody-positive infectious mononucleosis and stimulates the growth and immortalizes B cells in tissue culture Has been causally associated with AfBL (endemic Burkitt lymphoma), Hodgkin disease, and nasopharyngeal carcinoma EBV has also been associated with B-cell lymphomas in pts with acquired or congenital immunodeficiences

EC50 is a measure of potency. If EC50 is low, the drug has a

high potency If EC50 is high, drug has low potency

Bioavailability

is the extent to which an administered drug reaches the systemic circulation Most commonly refers to the comparison of the amt of drug absorbed from a dosage form to the amt delivered in an intravenous dose Calculating (absolute) bioavailability: F= AUC other (i.e. oral drug)/ AUC IV Ex: Drug given IV results in an AUC of 400mg/L x h . If the SAME dose of the drug is given orally and the resulting AUC is 300mg/Lxh, what percentage of the oral dose reaches the systemic circulation? F= 300/400= 0.75 (75% of the oral dose reaches the systemic circualtion) - this means the pt only gets 75% as much drug if they are given the drug orally instead of IV If you wanted to calculate bioavailability of one dosage form vs. any other, the formula above can be manipulated Ex: intramuscular bioavailability is calculated (AUC IM)/ (AUC IV) The area under the plasma drug concentration-time curve (AUC) reflects the actual body exposure to drug after administration of a dose - AUC is related to the total amount of drug that reaches the systemic circulation

Surfactants allow

mechanical removal of microbes - soaps and detergents - do not efficiently kill microbes - but can remove them efficiently

In research, relative risk and odds ratio are often paried with confidence intervals and/or p value

p<.05 (RR is significant) if confidence interval does NOT include 1--> value is significant

Fermentation test

pH indicators in the media reflect the production of acid from metabolism of a sugar in the medium; fermentation patters help with identification - Note that several differntial media use this type of test, but that these do not differentiate homo- (no gas production), from heterofermentation (gas production, caught in little tube). - Acid may also be produced oxidatively, rather than fermentatively * results back overnight

When compared to ibuprofen, naproxen can be

taken less frequently (longer half life in Naproxen) ** remember Naproxen is an NSAID and it relieves both pain and fever

Chi-square (X^2)

used for nominal/categorical data, determines whether observed differences in proportions between study groups are statistically significant - ex: lung cancer status in smokers vs. non-smokers Independent variables: nominal (categorical) Dependent: nominal (categorical) CANNOT be used with SMALL sample sizes

alpha2 receptor

- Adrenergic and cholinergic nerve terminals--> inhibits transmitter release - Some vascular smooth muscle --> contraction - Platelets --> Aggregation - Fat cells --> inhibits lipolysis

Gram positive NON-spore forming rods (bacilli)

- Corynebacterium diphtheriae - Listeria monocytogenes - Actinomyces israelii - Nocardia asteroides

Beta2 functions

- Promotes smooth muscle relaxation in respiratory and uterine smooth muscle - Increase aqueous humor production in eye; ciliary epithelium - Vasodilation; promotes potassium uptake in skeletal muscle - Activates glycogenolysis in liver

Nonselective Beta-antagonists

- Propranolol - Pindolol - Timolol MOA: Competitive inhibition of beta1 and beta2 receptors

AAMC guidelines for working with pt whose lang is diff from yours

- assess pts lang needs (spoken vs. written) - pay attention to your positioning - family members as interpreters: pros and cons? - conflict of interest? privacy? - check for understanding

Pathogenicity island

- clusters of genes, often multiple overons - acquired from other places/different G-C content (often transported by phages) - encode numerous virulence factors - contain transposable elements or remnants

What are the steps in Apoptosis?

1. Shrinkage of cell/cytoplasm with preservation of organellar (mitochondria, ER) structure 2. Condensation of chromatin 3. Formation of cytoplasmic blebs and apoptotic bodies: round-oval densely eosinophilic masses with dark-blue nuclear fragments (round or crescentic) 4. Rapid phagocytosis by macrophages and adjacent cells Two pathways are possible - Mitochondrial (intrinsic) pathway** - Death receptor (extrinsic) pathway

Flow Cytometry

A modification of immunofluorescence in which stained cells are passed through a laser beam and light refraction or scatter is analyzed to indicate the types and numbers of cell present (fluorescence activated cell sorter, FACS) ** Very powerful- used in many research and diag lab. * Fluorescence will be emitted from stained cells and be detected

Clinical uses of Choline Esters

Acetylcholine: - Induce miosis during surgery; corneal transplant, iridectomy and other procedures where rapid miosis is necessary Carbachol: - Lowers intraocular pressure in treatment of glaucoma - induce miosis during surgery Bethanechol: - Treatment of urinary retention (helps ppl urinate)

Antibotics that block the 30s ribosome (protein syn. inhibitors)

Aminoglycosides - via blockade of the initiation complex, misreading of the code of mRNA template, and blockade of translocation reaction Tetracyclines - via blockade of aminoacyl-tRNA binding

Antibiotics that inhibit protein synthesis

Aminoglycosides: - Gentamicin - Tobramycin - Amikacin Macrolides: -Erythromycin - Azitrhomycin - Clarithromycin Lincosamide: - Clindamycin Tetracylcines: - Tetracycline - Doxycycline - Minocycline Glycylcyclines - Tigecycline Other - Linezolid - Chloramphenicol - Quinuprisitn-Dalfopristin

Acanthamoeba culbertsoni

An Amoeboflagellate (Primary CNS Pathogen) **LESS aggressive than the other pathogen Naegleria fowleri Mode: infection of skin, eye, lungs, and other tissue especially in immunocompromised persons, may spread through blood to the CNS (granulomatous encephalitis)

earliest detectable indication of EBV infection

Atypical lymphocytes - Heterophile antibody can usually be detected by end of 1st week of illness and lasts for as long as several months

Sympathetic receptors working in the kidney include

Beta1: increases renin secretion D1: vasodilation-> increased blood flow and increase Na+ excretion

Isoproterenol has equal receptor affinity for

Beta1=Beta2

Cardiovascular effects of Isoproterenol IV Infusion

Beta1=Beta2 Increase in: - Systolic BP - Direct effect HR (beta1) - Reflex effect on HR - Final effect on HR Decrease in: - Diastolic BP (beta2) - MAP

Titer

Highest dilution of serum able to agglutinate a particular antigen - quantitative: compare to standards to obtain a concentration - semi-quantitative: reported as ratio based on dilution (1:*, 1:16, 1:32) or its invers (8,16,32) - qualitative: positive/negative, reactive/non-reactive Mix serial dilutions of serum with constant amount of antigen bound to particle/cell, look for agglutination- cross-linked particles WONT settle to bottom - Higher dilution means more specific antibody present initially

Recombination

Incorporation of extrachromosomal (foreign) DNA into the chromosome Homologous recombination: - occurs between closely related DNA sequences and generally substitutes one sequence for another - requires enzymes (rec genes) *** this type occurs most often bc genes have a tendency to bind more if they are closely related in sequence - if a better gene X binds with gene X maybe you end up with a better gene X Nonhomologous (illegitimate) recombination: - occurs between dissimilar DNA sequences - yields insertions of DNA or deletions or both - specialized recombinaton enzymes (sometimes site-specific) such as those produced by transposons and bacteriophages

Case Series

Reports of a group of similar cases, same disease - NO disease-free individuals included - Exposure(s) are included in the history - One focus is exploring for common exposures - Statistical test: NONE Ex: Case description of anti-NMDA receptor encephalitis in 13 Thai pts

Constitutive activity

Some drug targets (ex. enzyme, GPCR) are always active; this level of activity can be increased or decreased - Agonist: will increase activity, has positive efficacy (increases baseline activity) - Antagonist: will have NO effect on activity, no efficacy (neutral antagonist) - Inverse agonist will decrease activity, has a negative efficacy (inhibits baseline response) ** Other drug targets have no activity until they are activated by agonist - Agonist activates target; antagonist prevents activation by agonist

A normal cell (in homeostasis) can either undergo stress of injurious timulus

Stress--> Adaptation --> Inability to adapt--> cell injury Injurous stimulus--> Cell injury If cell injury is Mild, transient --> reversible injury--> return to homeostasis If cell injury is severe, progressive --> Irreversible injury --> Cell death (necrosis or apoptosis)

Microbial Resistance to Anti-Folates

Sulfonamides: - Acquired resistance to sulfonamides is now fairly common, mainly among Neisseria, Streptococci, Staphylococci, Shigella and Escherichia col - Resistance is persistent and irreversible - Acquired resistance is due to transfer of resistance by plasmids (the most common case) or to random mutation and selection Trimethoprim: - Resistant is due to a plasmid that codes for an altered dihydrofolate reductase - Resistance to trimethoprim-sulfametoxazole (TMP-SMZ) is lower than is resistance to either of the agents alone

Epinephrine reversal by an alpha-Antagonists

The conversion of the epinephrine pressor response (blood pressure raising) to a depressor respose (blood pressure lowering) in a pt who has received treatment with an alpha-antagonist Pressor response is mediated by (alpha1) and depressor response is mediated by (beta2) - alpha blockade to epi--> decreased BP bc beta2 is working unopposed The effect is NOT observed with phenylephrine or norepinephrine bc the durgs do NOT activate beta2

Pt Explanatory Models

The way a person explains the cause of illness: - why the onset occured when it did - effects of the illness - what course the illness will take - what treatments are appropriate - embedded in social/cultural contect ** Before transition from HPI to PMH. Ask an explanatory model question Ex: - what do you think has caused your problem? - why do you think it started when it did? - what do you think your sickness does to you? - how severe is your sickness? - what kind of treatment do you think you should receive? ***Pt centered care is one skill to strive toward cultural competence/humility- includes eliciting pts explanatory model

Pulmonary administration (gases)

To achieve SYSTEMIC effects: (via gases) Absorption pattern: - primarily by lipid diffusion through the alveolar membrane - rapid Advantages: - consciousness is not required - dosage is tightly controlled Disadvantages: - drug must be a gas or a volatile liquid - sophisticated equipment usually needed Ex: Nitrous oxide is an example of a medication delivered as a gas ------ To achieve LOCAL effects: (not gases but aerosols) Absorption: - primarily by lipid diffusion through the alveolar membrane Advantages: - drug concentration is locally high - systemic absorption is delayed and limited; adverse effects minimized Disadvantages: - specific equipment required Ex: Albuterol is an ex of medication delivered as an aerosol

When should Droplet precuations be used?

When there is efficient transmission by large droplets - Diphtheria - Meningococcal meningitis - Pertussis - Pneumonic plague - H. influenzae - Mycoplasma pneumoniae - seasonal influenze - mumps - rubella - adenovirus - parvovirus B19 - RSV - Ebola Use Standard Precautions +: - Private room/cohorting - Mask and eye protection within 3 ft of pt (cough falls below 3 ft bc droplets are heavy enough) - Mask pt if must leave room - Clean hands between tasks

Gastric emptying is the process by which the contents of the stomach are moved into the duodenum- what would a delay in gastric emptying do to drug absorption?

Will slow the rate and possibly the extent of drug absoprtion, thereby prolonging the onset time of the drug Things that hasten gastric emptying? - large amounts of fluids--> especially lukewarm ones - lying on the right side - some diseases (hyperthryoidism, chronic anxiety) - some drugs (metoclopramide, bethanechol) Things that delay gastric emptying: - solid foods--> espcecillay protein or lipid foos: gastric emptying can be delayed of several hrs - physical activity, pain, fear, cold, stress - some diseases (hypothyroidism, pyloric stenosis, gastroenteritis, diabetes, depression, etc. - some drugs (anticholinergics, sympathomimetics, opiods, aluminum salts, etc)

First step in cultural humility is

self-awareness of ones identity, beliefs, and biases - address privilege and implicit attitudes - we all have explicit and implicit biases (deeply ingrained through socialization...media messages, messages from your community, family, etc) - Gain knowledge about specific groups or cultures (individuals within a group may have heterogenous experiences) - Always take a pt centered approach: illness can ONLY be understood through pts perspective ** DONT make assumptions (you can always ask!)

A mutant receptor protein can continue to deliver mitotic signal even in the absence of growth factor (GF) in the environment-- the most common receptor proteins are

tyrosine kinases Example: Mutations of EGF receptors in breast and ovarian carcinoma: - Amplification of ERBB2 (HER2/neu) ** Treatment of breast cancer by blocking of extracellular doman by ERBB2 antibodies (Herceptin and Trastuzumab are drugs that do this)

Oncogenes like Nuclear Transcription factors are activated through

different cytosolic signaling pathways - They directly bind DNA and activate transcription of genes involved in cell growth and proliferation Families of transcription factors include: MYC, JUN, FOS, etc. MYC mutations: - C-MYC overexpressiondue to translocation t(8;14) in Burkitt Lymphoma - N-MYC (chr. 2): amplification in Neuroblastoma --(amplification stays in chromosome as homologous staining region (HSR) or split into Double minutes)

Motivational interviewing is the

process of helping ppl move through the stages of change with their own motivations

Sympathetic NS

prominents in times of stress and conditions that require energy expenditure - Activation accelerates heart rate, increases blood glucose, shifts blood flow from the skin and splanchnic region to the skeletal muscles and dilate the pupils and bronchioles

Gram negative rods (bacilli) that are related to the enteric and/or genitourinary tract

- Escherichia coli - Salmonella (S. typhi, S. enteritidis) - Shigella (S. dysenteriae, S.sonnei) - Vibrio cholerae, Campylobacter jejuni, Helicobacter pylori, Enterbacter cloacae - Serratia marcescens - Proteus (P. mirabilis, P. vulgaris) - Morganella morganii - Providencia rettgeri - Pseudomonas aeruginosa - Bacteroides fragilis - Klebsiella granulomatis

Innate defenses to Viral infections include

- Physico-chemical barriers - NK cells** - Phagocytic cells - Complement and acute phase proteins

Give examples of lipid accumulation

- Triglycerides: steatosis, or fatty change - Cholesterol: atherosclerosis, xanthomas, xanthelasmas, and cholesterolosis - Complex lipids: lipid storage diseases

How is the Plasma membrane of bacteria used as a drug target

- Unique composition - Disruption, usually by pore formation (destruction of chemical gradients, loss of nutrients and ions) Targeted by: - Cationic polypeptides (ex. Polymyxin B) - Newer glycopeptides (Target plasma membrane) - Lipopeptide antibiotics (ex. Daptomycin)

Most bacterial processes require several proteins, it is efficient to put them under same control mechanism- A number of "layers", major ones are:

- operon - regulon - stimulon ** these coordinate gene expression Regulon: - A further layer of coordination - multiple genes or operons under control of same regulators or the same promoter site - Different location on the chromosome - Allows a gene/operon to be used for diff. processes req at diff. times Stimulon: - Multiple genes, operones or regulons under control of the same stimulus via multiple regulators - Allow organism to react to an effect from multiple causes rather than one specific cause (ex. cell wall stress vs. individual classes of antibiotics) - NOTE: some genes/ operons can have numerous regulators

What are the functions of antibodies?

1. Agglutination of particulate matter, esp. bacteria and viruses. IgM is very efficient due to its structure 2. Opsonication of pathogens for phagocytosis 3. Neutralization of toxins and viruses 4. Immobilization of bacteria by binding to cilia or flagella 5. Complement activation and lysis of target cells 6. Mucosal protection: mainly by IgA 7. Parasite immunity- involving IgE and eosinophils 8. Immune complex formation- removal of soluble antigen 9. Antibody dependent cellular cytotoxicity (ADCC)- in collaboration with NK cells, eosinophils and other cells 10. Fetal protection- transplacental transfer of IgG

What are 5 strategies to reduce HAIs?

1. Hand Hygiene 2. Source control - surveillance and tracking- "fingerprinting" methods show relatedness between isolates - screening (staff, pts) and decolonization, vaccination 3. Isolation, source exclusion - standard/universal and isolation precautions 4. Cleaning/disinfection/sterilization - decontamination 5. Antimicrobial stewardship (working with pharmacists, nurses to give antibiotics in timely manner--> less time person sick less ability to spread)

Elements to Resolving Difficult encounters in a Positive Manner

1. Identify the problem (overt) 2. Recognize the dynamic involved (covert) 3. Determine which technique may be best applied for a good resolution (covert) 4. Apply (overt) Techniques for Resolution: Communication Skills + Non-verbal behavior Ex: A pt , who suffered heart attack, requests discharge before his treatment is completed... Determine WHY he wants an early discharge

Disadvantages to live vaccines (a type of active immunization)

1. Live organisms can pose a potential threat to individuals who cannot effectively resolve even a mild infection (ex. immunocompromised people or preg. women) 2. Attenuated virus strain may potentially revert to a virulent form (rarely seen for some vaccines such as yellow fever vaccine, to never documented as is the case for measles/mumps/rubella (MMR) vaccine) 3. Since organism is living, viability must be maintained until administration

What are the steps in Prokaryotic transcription?

1. RNA polymerase begins process by binding to promoter - -35, -10 seq. from transcriptional start - ideal seq varies between species or even genes - seq. and location affects efficiency - specialized molecules known as repressors and inducers also play roles in regulation 2. RNApol unwinds the DNA and then places ribonucleotides on template strand of DNA (reading template 3'-5') and synthesizing in the 5'-3' direction - there is NO proofreading making the error rate 10000 x DNApolII - there is also no primer (bc being synthesized in the 5'-3' direction 3. RNApol continues until it hits a terminator - Rho-dependent req. Rho protein, which binds a recognition site and destabilizes the RNA pol (pushes between the RNA polymerase and the DNA, releasing the polymerase- Rho protein moves along the RNA) - Rho-independent is a stem-loop-UUUU.. structure in the RNA which destabilizes the RNApol (aka self termination)- transcription of DNA term seq cause the RNA to fold, loosening the grip of RNA poly on the DNA (C-G rich stem loop present)

What are some factors affecting absorption?

1. pH changes 2. Membrane thickness & surface area 3. hepatic and GI metabolism (ex. first pass effect) 4. drug formulation (ex. dosafe form, particle size, etc) 5. Destruction by stomach acid (acid resistant enteric coating prevents this 6. Gastric transit time 7. Digestive enzymes (ex. pepsin) which may break down drugs

Adolescence

12-18 yrs Transitional stage from dependency of childhood relative independence of adulthood - applying abstract and complex concepts - identitiy and personal opinions formed - changes in behavior and social rols - concerned about their looks - interest in opp. sex, spend more time with their friends, less with parents Phys and Sexual develop: - puberty marks the onset of adolescence - renewed sexual curiosity at this time, and it is for sexual gratification Cognitive develop. - abstract thinking - some remain as concrete thinkers as adults (about 10%) Personality and moral dev: - will challenge rules - preocuppied with moral and ehtical issues - develop their conscience as individuals and establish long-time life goals Social factors affecting deve: - peer group pressure - risk taking behavior: drugs, sex, preg - occupational choice ***expectation= at end of adolescence an individual becomes a well adjusted, productive adult

Constructivism vs. Essentialism

2 ways of specifying medicines goals and reason for being Social constructionist view: - diverse social factors and cultural values shape healing practices - medicines end and puposes are externally determined and culturally variable Essentialist view: goals of medicine are derived internally from invariant and unchanging values inherent in the practice of medicine - preventing and curing disease - relieving pain - mitigating suffering Hastings center project: encouraged dialogue between constructivists and essentialists to arrive at a consensurs, with understanding that the risk to medicines integrity and to the best and highest for pts increases when the balance between these 2 views is skewed too far toward one or the other- the pt consisted of indivduals from humanitites, biomedical sciences, clinical med, social sciences Modern medicines goals and limits: - disease prevention, health maintenance and promotion - relief of pain and mitigation of suffering caused by disease or injury - care and cure of those with an ailment, and care for those who cannot be cured - avoidance of premature death and pursuit of a peaceful death

Quinupristin/Dalfopristin

A combination of two semisynthetic derivatives of streptogramins, a group of antibiotics produced by Streptomyces species MOA: - Quinupristin binds to the 50S ribosomal subunit and blocks the translocation rx. - Dalfoprisitin binds to the 50S ribosomal subunit so inducing a conformational change in the 50S ribosome that enhanves the binding of quinupristin **** Effect of qunupristin alone or dalfopristin alone is bacteriostatic, but the effect of the 2 drug combination is rapidly BACTERICIDAL, with a long post antibiotic effect

Enzymatic Fat Necrosis

A focal areas of fat destruction resulting from abnormal release of activated pancreatic enzymes into the substance of the pancreas and peritoneal cavity - Etiology: acute pancreatitis - Mechanism: injury of acinar cells --> release of lipase--> release of fatty acids from neutral fat --> binding with calcium (saponification) Gross appearance: chalky-white calcium deposits Histology: - shadowy outlines of necrotic adipocytes - basophilic (blue) amorphous calcium deposits

How can ABL protein cause cancer?

ABL protein= intranuclear tyrosine kinase with a normal function of promoting apoptosis Mutation: t(9;22)--> fusion of ABL with BCR with synthesis of ABL-BCR hybrid - Hybrid is TOO large to enter the nucleus--> remains in the cytoplasm--> activates cytosolic pathways--> Chronic Myeloid Leukemia (CML) Treatment of CML: Gleevec (Imatinib)--> blocks activity of hybrid, neutralizes kinase activity and promotes apoptosis

Risk assessment of IPV

Abusive tendencies: - Telling vitctim then can never do anything right - controlling every penny - intimidating victim with violence - accusing victim of cheating - controlling victoms actions - pressuring victim for sex - keeping them from seeing friends/fam - dictating how they dress - pressuring drug/alcohol use - embarssing/shaming - stalking - destroying victims property Physical finding - central pattern of abuse (face, neck chest, breast, abdomen, genitalia) - multiple injuries in various stages of healing - bruising on inner aspect of arms and legs - injuries suggestive of defensive posture (ulnar aspect of forearms) - human bite marks - unexplained burns or scalds - unexplained fractures

Describe Attachment of a virus

Adhesin-receptor interaction Viral Attachent Protein (VAP) - Naked viruses: capsid protein - Enveloped viruses: membrane protein, usually glycoprotein Host cell receptors: proteins, glycoproteins, carbohydrates, glycolipids ** Attachment determines host susceptibility (if it "CAN" get infected) ** This process is blocked by antibodies it is a vaccine target

ADDRESSING

Age & Generation Developmental Disability (Dis)ability Religion Ethnicity/Race Socio-economic Status Sexual orientation Indigenous Status National Origin and Language Gender

Differentiate between Alphaherpesvirinae, Betaherpesvirnae, and Gammaherpesvirinae

Alphaherpesvirinae: - varibale host range - SHORT reproductive cycle - rapid spread in culture - destruction of infected cells - usually establish latency in sensory ganglia Includes: - HHV-1 (Herpes simplex virus 1) - HHV-2 (Herpes simplex virus 2) - HHV-3 (Varicella-zoster virus) Betaherpesvirinae - restricted host range - long reproductive cycle (>7d) - SLOW spread in culture - cytomegalia - establish latency in many TISSUES Includes: - HHV-5 (Human cytomegalovirus) - HHV-6 (Roseolovirus) - HHV-7 Gammaherpesvirinae: - Restricte host range - Replicate in lymphoblastoid cells - Can be lytic for epithelioid and fibroblastic cells - usually specific for B and T lymphocytes - Usually establish latency in lymphoid tissues Includes: - HHV-4 (Epstein-Barr virus) - HHV-8 (Kaposi sarcoma-associated herpesvirus)

What type of vaccine is Measles, Mumps, Rubella (MMR)

Attenuated - should be given to children

What are methods used for the Laboratory Diagnosis of cancers?

Biopsy: - Excisional (whole thing) - Incisional (piece) - Frozen section technique (taking a piece during surgery- and pathologist gives results in 15 min) Fine needle aspiration biopsy (FNAB) Cytology (Pap smear) Immunohisto (cyto) chemistry Flow cytometry Fluorescent in situ hibridization (FISH)

BCL-2 gene overexpression aids in

Evasion of Apoptosis t(14;18)--> Overexpression of BCL-2--> Blockage of cytochrome c release from mitochondria--> Inhibition of apoptosis --> Neoplastic growth (follicular lymphoma) ** IgH locus--> overexpression of BCL-2 gene

What are inherent host factors that influence pathogenicity?

Genetic (host): - disruption of genes encoding host immune responses or intrinsic defense mechanisms - certain alleles Other factors that can be involved in pathogenicity of viral infections include: - Transmission modes - Geogrpahy (reservoirs, vectors) - Seasonality (environmental factors, vectors) Host susceptibility: - immunity - genetic susceptibility (ex. MHC make up) - age - gender - pregnancy - malnutrition - corticosteroid levels (ex. stress) Crowding Socioeconomic conditions

Spirochetes

Gram-negative - Have flagella between PG and OM= endoflagella - Turing of flagella causes flexible body to twist, propelling organism - VERY thin, so not visible by light microscopy (gram stain is not useful, use dark field microscopy, or flourescence microscopy) Includes: - Treponema (causes syphilis), Borrelia (causes lyme disease), Leptospira

Which NSAID is - available OTC - effective in closing patent ductus arteriosus in preterm infants, with much the same efficacy and safety as indomethacin - less GI toxicity that other NSAIDs

Ibuprofen

Ganglionic Blocking Drugs include

Mecamylamine

Numbers Needed to treat (NNT)

Number of pts who would need to receive treatment for one pt to benefit ** used to determine the effectiveness of a treatment in RCTs*** Calculated by taking the reciprocal of the attributable risk between experimental groups Another way is dividing 100 by absolute risk (%) NNT= 100/Absolute risk (%)

Ca-125 is a marker for

Ovarian carcinoma

Nonselective Beta-Antagonists (Beta1 and Beta2)

Propanolol Pindolol Timolol

Onchocerca Volvulus

River blindness/Onchocerciasis Mode: - Vector bite- Simulium blackfly (breeds in river) Disease: - larvae in nodule in subcutaneous tissue - skin (dermatitis) - eye (blindness) Diagnosis: - Nodulectomy (skin snip)

T or F: Aspirin, Ibuprofen, Naproxen, Acetaminophen are all available OTC for pain and fever

True!

Ecological Study

Use population level data or group level data - used to measure incidence and/or prevalence - can be cross-sectional or longitudinal - good for tracking rare diseases Ex: Sugar consumption vs. prostate cancer in 71 countries

What is a bacteriophage?

Viruses that infect bacteria - can be complex, icosahedral or filamentous - transfer genes from one bacterium to another via transduction (ex. diphheria toxin, cholera toxin) - potential use as anti-bacterial agents

Full agonist has greater efficacy than

partial agonist - This might be described using decimals, such that full agonist has efficacy=1 - Partial agonist has efficacy less than 1, but greater than 0 Efficacy may also be described using percentages, such that full agonist has 100% efficacy and partial agonist has efficacy greater than 0% but less than 100% - Antagonist has 0% efficacy, as it does NOT produce an effect (its effect is to prevet the agonist from activating the receptor) - Inverse agonist: has negative effecacy, which can be described as less than 0 or less than 0%. For the inverse agonist illustrated on the left graph, its efficacy is perhaps about ~25% (or ~0.25)

Tranplant recipients undergoing immunosuppressive treatment are at high risk of _____, instead of infectiou smon o when expose to EBV or on reactivation of the latent virus

posttransplant lymphprolifferative disease

An interim report can be used to

reduce the number of possible antibiotics that may be prescribed

Virus tissue tropism (i.e. cell susceptibility & permisiveness) determines the

tissues infected and therefore the disease caused

What are some microscopic features of myocardial hypertrophy?

- increased size of cardiomyocytes - increased size of cardiomyocyte nuclei - boxcar nuclei

Selective Beta1-Antagonists

Atenolol Esmolol Metoprolol

What are the 4 main types of protozoa (based on motility) - protozoa are unicellular organisms, the first "animal"

- Amoebae (rhizopoda, sarcodina) --> pseudopodal motility - Flagellates (mastigophora) --> flagellate motility - Ciliates (ciliata)--> cilia assisted motility - Sporoza (sporozoa)--> gliding motility

Affects of alpha1

- Contraction in Most vascular smooth muscle - Contraction (mydriasis) in pupillary dilator muscle - Contraction of the Prostate; urinary sphincter

NSAID drug interactions

- Counteract the effect of some antihypertensive drugs- due to their ability to cause salt and water retention - Increase the bleeding time if co-administered with warfarin (or other anticoagulants) - Cause negative renal effects if co-prescribed with angiotensin convertine enzyme inhibitors (ex. enalapril) - Increase the risk of GI bleeding if used with alcohol

Koch's Postulates

- Identify in all diseased organisms - Isolate and grow in pure culture - Introduce into healthy model- should cause disease - Reisolate- from model and demonstrate identity to original In steps: 1. Suspected germ must be present in every case of the disease 2. Germ must be isolated and grown in pure culture 3. Cultured germ must cause the disease when it is inoculated into a healthy, susceptible experimental host (animal or plant) 4. Same germ must be reisolated from the diseased experimental host Exceptions to Kochs Postulates: - Not culturable - Not universally disease-causing - No animal model - Polymicrobial diseases - Acquired virulence factors Molecular Koch's Postulates: - Identify: phenotype/gene in pathogenic strains but not others - Alter: gene manipulation should affect virulence - Restore: gene recovery should restore virulence

Affects of alpha2

- Inhibits transmitter release in adrenergic and cholinergic nerve terminal - Decreases aqueous humor production in ciliary epithelium - Decreases insulin secretion in pancreatic beta-cell - Aggregation in Platelets - Lipolysis in Fat cells

Lab diagnosis for HHV-4 or EBV (epstein barr virus)

- Lymphocytosis - Atypical lymphocytes (CD8 T cells or NK cells) - Downy cells & NK cells Serology: - Anti-EA: expressed in acute phase if have symptoms this and IgM --> infectious mono - Anti-VCA: when pts mostly recovered viral capsid antigen (VCA) isotype switches to IgG - Anti-EBNA: Anti Epstein Bar Nuclear Antigen appears when virus is in latency with IgG

How is Alphaherpesvirinae Diagnosed?

- Nucleic acid testing/cuture - Immunofluorescence (GOLD STANDARD!) - Serology (ELISA or Immunoblot)- good for ppl who are asymptomatic bu tnot affected i.e. for preg women passing on to fetus - Tzanck smear: staining of lesions, many viruses will give (+) Tzanck smear

What methods can be used for detection of Nucleic Acids?

- PCR, RT-PCR (reverse transcriptase), real time PCR - Amplification leads to reasonable SENSITIVITY - Based on unique NA sequence so very SPECIFIC - Rapid, BUT most on cultured material - Can be mutiplexed- test for multiple potential pathogens at same time When is nucleic acid testing useful? - Dificult-to-cultivate organisms: obligate intracellular organisms, unculturable, high risk - Multiple possible causative agents - Need for quantitation (ex. tracking viral loads) - quick result - early result: low pathogen numbers, no waiting for immune response

RNA viral genomes can be

- Positive- sense (polarity), single-stranded--> (+)ssRNA - Negative-sense, single-stranded (-)ssRNA - Ambisense (can read in both direction) - Double-stranded (dsRNA) - Single-stranded with iDNA (intermediate DNA)

Describe Post-translational regulation of prokaryotes

- Protein modification can control enzyme activity - FASTEST response - alters conformation - some irreversible: part cleaved off, degradation - usually reversible: phosphorylation, acylation Ex: Proteolysis - Pre-pro diphtheria toxin (inactive) undergoes proteolytic processing to become: - Pro-diphtheria toxin (inactive--> more proteolytic processing to yeild a disulfide bond to link A and B chain giving the - Mature diphtheria toxin (active) * If A portion released from diphtheria toxin it inactivates elongation factor-2 and it prevents protein synthesis on ribosome leading to cell death

What components of viral structure can help to determine survival in the environment, resistance to disinfectants, and protection from host barries?

- Proteins (capsid): resistant to drying, temperature, detergents, bile, acid - Lipid (membrane): dries out, melts, dissolves - Some solvents, strong oxidants, UV will affect both proteins and lipid ** Can effect viral structure and virion transmission

How do I use gloves correctly?

- Put on new gloves b4 contact with mucous membranes or non-intact skin - Wear gloves during contact with bodily fluids or contaminated items - Remove gloves after caring for a pt- do not wear the same gloves for more than one pt - Do not reuse or wash gloves - Dont forget hand hygeine after removing gloves- Gloves are not a replacement for hand hygiene

List some types of Necrotic changes observed with Light Microscopy

- Pyknosis (greek "pyknos"- thick, crowded): nuclear shrinkage and increased basophilia - Karyorrhexis (greek "rrhexis"- rupture): fragmentation of pyknotic nucleus ("nuclear dust") - Karyolysis: nuclear dissolution (can follow karyorrhexis or develop ab novo *** this is the MOST reliable hall mark of necrosis - Increased cytoplasmic eosinophilia (loss of RNA and binding of eosin to coagulated proteins)

What are some specific serologic tests based on precipitation?

- Radial Immunodiffusion (Mancini) - Ouchterlony - ELISA - Immunoblotting - Immunoflourescence - Flow cytometry - Radioimmunoassay - Complement Fixation test

beta2 receptor

- Respiratory and uterine smooth muscle--> promotes smooth muscle relaxation - Skeletal muscle --> vasodilation; promotes potassium uptake - Liver--> activates glycogenolysis

Gram positive staphylococci

- S. aureus - S. epidermidis, S. saprophyticus

Describe some features of Gram-positive bacteria

- Thick layer of PG, no outer membrane - Contains teichoic acids and proteins & lipoteichoic acids - Stronge cell wall helps resist deformation upon desiccation (often see gram positives in drier environments (soil, skin) ** most often found on skin and fomites bc they can tolerate external environment for a long period of time

Describe and list Gram-negative genera

- Thin layer of PG - Outer membrane with LPS and porins Many genera... - Escherichia - Klebsiella - Citrobacter - Enterobacter - Serratia - Salmonella - Shigella - Yersinia - Proteus - Vibrio - Campylobacter - Helicobacter - Bacteroides - Pseudomonas - Burkholderia - Stenotrophomonas - Neisseria - Haemophilus - Moraxella - Acinetobacter - Bordetella - Brucella - Pasteurella - Legionella - Francisella - Kingella - Actinobacillus

What are the steps and 2 periods of the viral replicative cycle?

1. Attachment 2. Entry 3. Uncoating 4. Replication 5. Assembly 6. Release 7. Maturation *** each of these steps works as a target of a drug or vaccine What are the 2 periods of Virus Replication: * First NOTE: virions DO NOT replicate, they assemble 1. Eclipse Period: - virions are disassembled, none yet formed 2. Latent Period: - time to release off first virion ** Yield: number of virions released by an infected cell (burst size)

Ethical principles in clinical practice

1. Autonomy: - individuals rights to choose or refuse treatment - informed consent 2. Nonmaleficence: - "first do no harm:" - avoid unnecessary or unjustified harm 3. Beneficience - do as much good as u can 4. Justice: - fairness and equity- similar cases must be treated alike; just dsitribution of resources

List the steps of the "Rolling circle mechanism" in conjugation

1. Donor cell attaches to a recipient cell with its pilus. The pilus draws the cells together 2. The cells contact one another 3. One strand of plasmid DNA transfers to the recipient 4. The recipient synthesizes a complementary strand to become an F+ cell; the donor synthesizes a complementary strand, restoring its complete plasmid

What are 3 mechanisms of entry for a virus?

1. Endocytosis: - phagocytosis - endocytosis (clathrin, calveolin) - macropinocytosis 2. Membrane fusion: - enveloped viruses 3. Can be MIX od endo/fusion **These are targets of some antiviral drugs (ex. fusion inhibitors which can be used for HIV) and these can also be blocked by antibodies

List the steps of the Communications Pyramid from Base to top

1. Ethics & Multicultural Competence - Ethical obligations typically exceed legal duties - Multicultral practice: be aware of your own assumptions, values, and biases- know the worldview of the culturally diff pt and develop appropriate strategies and techniques a. Competence: boundaries of competence, biases and referral sources and knowledge b. Informed consent: pts are fully aware of whats happening, written consent c. Confidentiality: mandated reporters- exceptions to confidentiality d. Power: use power carefully and respectfully, dual relationships/power differentials e. Social Justice: i..e Abortion, abuse, medical futility, artificail insemination, assisted reproduction, capital punishment, gene therapy 2. Attending Behavior (encourages pts to talk) Major Fx: encourage talking with attending, discourage client talk with non-attention, teach clients attending skills as treatment supplement Results: communicate interest in pt talk, increase awareness of pts attending pattern, modify your attending pattern to achieve specific results - attend when interview becomes confusing - Use S.O.L.E.R 3. Open & Closed questions Open: Who, What, When, Where, How, What? - used to begin an interview and open new topics and pinpoint/clarify details - "How might you be helped today?" - "What more can you tell me about that?" - Elicit longer answers & gather more info, identify specifics, assist with pt/situation assessment "What would be your ideal situation?- Help elaborate and enrich the pts (his/her) story- "What might we have missed so far?" Closed: Focuse the interview, reveal specific deetails, close down pt talk, increase interviewe control 4. Observation Skills - increase your ability to onserve what occurs between you and your pts in interview - guide you to key issues in the here and now of the interview - help you respond appropriately to both individual and multicultural differences - Perceptual indices= filters (life experiences, culture, respect, self-image, religion, prejudice, biases, background, trust, parents, sex&gender roles, likes and dislikes) - Non-verbal behavior: how do we make meaning of nonverbal behavior? - Verbal behavior: How do you and ur pts use lang? Discrepancies and conflict-coping with the inevitable stressful incongruities- increase your ability to observe what occurs betwen you and your pts in interview - Observation styles (associated with varying individual and cultural ways of expression)- how can you flex intentionally and avoid sterotyping in your observation? 5. Encoraging, Paraphrasing and Summarizing - Active listening: demands that you participate by helping the pt clarify, enlarge, and enrich their story - Encouragers: gestures, phrases, repetition (i.e. positive facial expression, "uh-huh", repeat key words from last statement, silence with appropriate nonverbal behavior - Paraphrase: shorten, clarify, and feedback others comments- briedly state essence of pts talk in summary form, stay true to pts ideas but dont repeat them exactly - ask for feedback on accuracy and usefulness of your paraphrase - Summarizing: clarify and feedback lengthy and complex discussions- restate key pts to pt accurately, check for accuracy at the end * this may help an overly talkative pt stop repeating the same facts or story, thus speeding up and clarifying the interview process 6. Reflection of Feeling 7. 5-stage interview structure 8. Reflection of Meaning 9. Determining Personal Style

What are the steps in Chemical Carcinogenesis?

1. Initiation: exposure to a carcinogen with following irreversible heritable mutation--- initiation alone does NOT lead to formation of a neoplasm 2. Promotion: proliferation of neoplastic cells (= formation of a tumor) ** Promoters alone CANNOT cause neoplastic transformation (it is proliferation of already mutated cells that leads to neoplastic growth)

What are the structural changes involved in cell injury?

1. Reversible injury: injury of membranes with increased permeability (both cyto- and organeller membranes) 2. Somewhere here: point of no return 3. Irreversible injury: rupture of membranes - mitochondrial membrane--> inability to restore generation of ATP - cytomembrane--> leakage of intracellular proteins into the blood --> specific markers of organ injury - lysosomal membrane --> autolysis 4. Cell death (postmortem cellular changes)

Drug targets: physiological receptors, types

1. Steroid (intracellular) 2. Membrane enzyme 3. Tyrosine kinase associated 4. Ligand gated ion channel (ionotropic- ions move across membrane) 5. G-protein coupled (metabotropic- cause change in metabolism--> activate processes that produce second messengers)

5 LOX inhibitors (ex. zileuton) inhibit

5-Lipoxygenase

When might a loading dose be given?

A loading dose may be given when the infusion is initiated so that the pt receives the required therapeutic concentration from onset Ex: Digoxin used in cardiac falure; its half-life is about 40hrs. It would be too long to wait 160 hrs in order to achieve the plasma concentration needed to manage a serious cardiac failure

Cell injury

A sequence of events that occur, when the limits of adaptive capability are exceeded, or no adaptive response is possible Classification/steps: - reversible injury - irreversible injury= cell death Types of cell death in irreversible injury: - Necrosis - Apoptosis - Necroptosis - Pyroptosis - NETosis

Indirect ELISA is looking for

AB - Specific Ag used to capture specific Abs from patient serum - Detected with labeled anti-human Ab (indirect) - Quantitative if compared to standard curve

MOA of Antimuscarinic Drugs

ALL antimuscarinic drugs competitively inhibit MUSCARINIC receptors - effectiveness of this blockade (that is the affinity for the receptor) varies with the antagonist and with the sensitivity of the tissue - Atropine and scopolamine block ALL subgroups of receptors (M1-M3) - Other antimuscarinic drugs may have selectivity for one or another subgroup of muscarinic receptors Tertiary antimuscarinic drugs have negligible blocking activity at ganglionic Nn receptors Quaternary compounds (glycopyrrolate and ipratropium) mainly block muscarinic receptors but also exhibit blocking activity at ganglionic Nn receptors

Describe Encapsidaiton in the Lytic cycle of herpesviruses

ATP-depending packaging of dsDNA - Cleavage mediated by interaction with PORT (capsid portain protein), TER1 (heterodimeric terminase 1) and TER2 (heterodimeric terminase 2), TERbp (TER-binding protein), and PCP (portal capping protein) - Capping of nucleocapsid (PCP): portal capping protein; pressurized and very rigid) - Proteolytic process of scaffold proteins

Basic Stages of Viral Diseases

Acquisition and infection - Akin to colonization (entry into body and cells) Initiation of infection - Replication at primary site of infection; responsible for non-specific, general sxs like fever or malaise Incubation period - viral amplification and spread to secondary sites of infection Replication in target tissue - responsible for characteristic signs and symptoms Immune responses: - responsible for limiting disease and/or contributing to disease Transmission: can occur at ny point between stage 2- and past stage 7 - responsible for contagion Resolution of disease or persistent infection **Viral diseases can be experienced by the host as sets of defined steps- they are following: the incubation period, the symptomatic period, and resolution of disease (convalescence or healing)

Pt presents with sudden onset progressive pain, swelling, and redness of left knee jt - high grade fever for past 2 days - WBC count of joint effusion > 50,000/microL - gram stain: gram positive cocci in clusters - culture: coagulase-positive staph aureus Dx?

Acute purulent (septic) arthritis

What are the advantages and disadvantages of detection of specific antibodies against a particular pathogen?

Advantages: - usually very sensitive and specific - can tell if protective titer exsists - IgM antibodies indicate acute or active infection - Monitor progression (titer up or down) Disadvantages: - IgM antibodies only early in infection (7-10 days) - IgG antibodies may not appear for 2-4 weeks - May not know if infection past or current

After a gram stain you find that bacteria is gram-positive bacilli, that is endospore forming (spores not always produced in vivo)- what should be the next step to identify the bacteria?

Aerobe vs. Anaerobe Aerobe? Bacillus - found in soil and water - catalase + Anaerobe? Clostridum - found in soil, water, GI tract - catalase -

Epidemiological Factors of Cancer

Age - Frequency of cancer increases with age** - With carcinoma as the most common type of cancer overall - Peak of cancer mortality: 55-75 yrs - Due to accumulation of somatic mutations Tumors in young adults: - Leukemia - Lymphoma - CNS and soft tissue tumors (sarcomas) Tumors of Infancy and childhood: - Acute leukemia - Blastoma: neuro-, retino-, hepato- and nephroblastoma - Hepatocellular carcinoma - Soft tissue tumors (rhabdomyosarcoma) Ethnicity Geographic factors Environmental factors (occupational hazards)

Carbon particles can be acquired from

Air pollution, coal dust (Ex: anthracosis) - Inhalation --> alveolar macrophages --> accumulation of carbon particles in the lymphatics and regional lymph nodes Tattooing - Dermal macrophages

Eye Effector Organ Response to Symp and Parasymp NS Activation

Alpha1 (symp)--> Contraction (mydriasis) of the radial muscle/dilator pupillae, iris M3 (parasymp)--> Contraction (miosis) of sphincter muscle, iris M3 (parasymp)--> Contraction for near vision of the ciliary muscle, tension of the trabecular meshwork causes outflow of aqueous humor Beta2 (symp)--> Relaxation of ciliary muscle for far vision Beta 2 (symp)--> increased production of aqueous humor in ciliary epithelium Alpha2 (symp)--> decreased production of aqueous humor from the ciliary epithelium M3 (parasymP)--> secretion from lacrimal glands Ex: How do you reduce aqeous humor in th anterior chamber? - Ciliary epithelium- production (increase beta2, decrease alpha2) - Ciliary muscle- increase outflow/drainage (M3) Ex: A pt overdosesd on diphenhydramine, a drug that blocks muscarinic receptors. What are the signs related to the eye that may be experienced by this pt? - Pt will complain of photophobia (sensitivity to light) - Physican could observe dilation, increase aq. humor and increase intraocular pressure

Direct Acting Selective alpha-agonist drugs

Alpha1-agonists: - Phenylephrine Alpha2-agonists: - Clonidine - Apraclonidine

What type of vaccine is Varicella-zoster

Attenuated - should be given to children

ERBB2 (HERs/Neu) and Estrogen receptors are both markers for

Breast carcinoma

Celecoxib is a SELECTIVE

COX-2 inhibitor - Unlike the inhibition of COX-1 by aspirin (which is irreversible), the inhibition of COX-2 by celecoxib is reversible - COX-2 selective inhibitors have anti-inflammatory, antipyretic, and analgesic properties similar to the traditional NSAIDs, but they do not share the antiplatelet actions of the COX-1 inhibitors ** All other NSAIDs in the drug list are non-selective, reversible inhibitors of COX (except for aspirin which is irreversible)

Carcinoma vs. Sarcoma

Carcinoma: - origin epithelia - in adults; peak at 55-75yrs - more common - relatively slow-growing - cells arranged in groups (except anaplastic carcinoma) - well-formed stroma - Early lymphatic meta - Late blood-borne meta Sarcoma: - Mesenchyme/mesoderm origin - Can affect any age - incidence less common - usually rapidly growing - cells arranged in diffuse sheets - poorly-formed stroma - lymphatic meta are UNCOMMON - early blood-borne meta

Odds Ratio (OR)

Case-control studies: compare disease group with control - A measure of association comparing the odds of disease of those exposed to odds of disease among those unexposed - calculated in case control studies by calculating the odds of exposure among the cases to that among the control OR=(a/c)/(b/d) = ad/bc OR= 1 (no association) OR<1 (protective effect)

What are some causes and examples of Pathologic atrophy?

Chronic ischemia--> organ atrophy (can lead to brain atrophy- smaller and narrower gyri and wider sulci, if atrophy is symmetrical it is most likely Alzhiemers) Bone fracture --> immobilization --> skeletal muscle atrophy and osteoporosis Denervation (peripheral nerve damage)--> skeletal muscle atrophy Hypothalamic/pituitary injury--> atrophy of target organs (ex. thyroid or adrenal glands) Pressure atrophy - Increased intracranial pressure in hydrocephalus )i.e. dilated lateral ventricles)--> brain atrophy - Aortic aneurysm in (tertiary) syphilis--> atrophy of vertebral bodies - Urolithiasis--> hydronephrosis--> kidney atrophy - Cystic fibrosis --> obstruction of pancreatic ducts --> atrophy of exocrine pancreas (acini and intercalating ducts)- wider lumen and epithelium smaller Inadequate nutrition

Relative risk (RR) aka risk ratio is used in

Cohort studies

Example of Cyclins and CDKs that act as Oncoproteins

Cyclin D - t(11;14) --> CCND1 (cyclin D1 gene) overexpression --> can lead to Mantle cell lymphoma or Multiple myeloma Cyclin D can also do Amplification CDK4 can also do Amplification

Idealization

Deal with emotional conflict or internal or external stressor by attirbuting exaggerated positive qualities to others

Describe 3 types of Specimens

Direct from sterile site (best type) - suprapubic needle specimen of urine, bronchoalveolar lavage fluid - all organisms significant From sterile site through site with normal microbiota - midstream urine specimen, sputum - only pathogens are significant Sites with normal microbiota: - oropharynx, GI tract, skin, female genital tract, urethra - many organisms, some of pathogenic genera..are they significant?

DNA viruses can either be

Double-stranded I. Enveloped: - Pox- - Herpes- II. Naked: - Papilloma- - Polyoma - Adeno- Partial ds (gapped): I. Enveloped - Hepadna- (iRNA) Single-stranded: I. Naked - Parvo

Transdermal administration

Drug applied and "goes through the skin"- used when a sytemis effect is desired Absorption pattern: - primarily be lipid diffusion - slow and sustained Advantages: - bypasses the first-pass effect - convenient and painless - ideal for drugs that are lipophilic and have poor oral bioavailability - ideal for drugs that are quickly eliminated from the body Disadvantages: - some pts are allergic to patches, which can cause irritation - drugs must be highly lipophilic - may cause delyaed delivery of drug to pharmacological site of action - limited to drugs that can be taken in small daily doses

A decreased response to a drug, caused by prior exposure to that drug or to a related drug is referred to as

Drug tolerance -> tolerance= decrease in sensitivity to a drug Features: 1. Tolerance is evident only with some drugs 2. Tolerance can be overcome by increasing the dose 3. The amount of tolerance can vary widely 2 mechanisms of tolerance: 1. Pharmacokinetic tolerance (aka Metabolic tolerance) - tolerance is due to a decrease in the effective concentration of the drug at the site of action (ex. the drug increases its own rate of biotransformation by inducing drug metabolizing enzymes) 2. Pharmacodynamic tolerance (aka Functional tolerance) - tolerance to a drug whose concentration at the site of action is not modified, is due to: a. Homeostatic adaptive changes (neurophysiologcial or biochemical) that counteract the drug effect b. Changes in number of receptors of the drug (changes in number of receptors, i.e. down-regulation, is the most common mechanism) c. Changes in receptor signaling (ex. signal transduction pathway)

Ion Trapping

Drugs become trapped when present in the ionized form so depending on the pH of the medium- drugs can therefore concentrate in specific compartments Ex: Treatment of salicylate poisoning utilizes the ion trapping theory - BOTH the ionized and unionized molecules are filtered by the glomerulus HOWEVER only the unionized molecule can be reabsorbed. Alkalinizing the uring (making the pH >7) with sodium bicarbonate is used to treat salicylate poisoning Salicylate is a weak acid with a pKa of 3. If the pH >7, the RCOO- (or A-) form will predominate- pH >pKa for a weak acid - therefore the ionized molecules will remain in the urine (trapped) for excretion (and re-absorption is prevented) NOTE: - Aspirin is classified as a NSAID and toxicity may occur when persons do NOT take the drug as recommended- changing pH can be used to manage aspirin overdose/toxicity

Psammoma bodies are a type of

Dystrophic calcification Seen in: - ovarian carcinoma - thyroid carcinoma - meningioma NOTE: - Calcific degeneration of aortic valve, can lead to aortic stenosis Reasons for cusps thickening? - abnormal valve is a subject to more wear and tear, and undergoes dystrophic calcification

After wood becomes embedded in pt finger it becomes red, swollen and tender- neutrophils migrate into the injured tissue - Expression of what on endothelial cells is most instrumental to promoting inflammatory reaction?

E-selectin? check this!

Burkitt lymphoma

EBV induces only polyclonal proliferation of B- cells Additional triggers are required for t(8;14) --- like Malaria in an endemic area Non-endemic Burkitt lymphoma arises from direct t(8;14) without EBV infection **** Lymphocytes are seen in infectious mononucleosis as is characteristis "Starry Sky" with macrophages that are clear

Active transport processes can be used to transport drugs of exceptionally large size across the cell membrane- what are two mechanisms that do this

Endocytosis and Exocytosis Endocytosis: - engulfment of drug by cell membrane and transport into cell by pinching off the drug-filled vesicle - may be receptor mediated: specific cell surface receptors bind the molecule which must be engulfed Ex: hormones, growth factors, transport proteins that carry cholesterol (low-density lipoprotein) or iron (transferrin), antibodies etc. Exocytosis: - secrete substances out of the cell through a similar process of vesicle formation Ex: Transport of protein such as insulin from insulin-producing cells of the pancreas into the extracellular space- the insulin molecules are first packaged into intracellular vesicles, which then fuse with the plasma membrane to release the insulin outside the cell ** Some drugs are too large to pass through the plasma cell membrane or to move through a transport protein - Very large molecules up to MX 100,000 D can enter cells by endocytosis

CD31 is a marker for

Endothelial (blood vessel) tumors

Fibrinoid Necrosis

Extra-, not intracellular, degeneration Accumulatin of deeply eosinophilic amorphous material within injured/necrotic vessel wall - fibrinoid: a new protein containing fibrin, collagen, and vessel wall components - loses water and converts to hyaline (not a cartilage- see accumulations) Usually indicates severe vascular injury Causes: - Physiologic condition: utero-placental arteries during normal pregnancy - Pathology: arterial hypertension or immune-mediated vasculitis Gross appearance: not changed Histology: accumulation of deeply eosinophilic amorphous material within the vascular wall Significance: - Irreversible (progresses to hyalinization) - Inhibition of metabolite transport - Rupture of blood vessel wall and hemorrhage

Keloid

Exuberant fibrous proliferation extends beyond the borders of the original wound, does not regress spontaneously, often recurs after excision Keloid should be differentiaed from hypertrophic scar: does not extend beyond the original wound borders scar and can regress

Social factors affecting development during child hood

Family circumstances - phys and emotional needs - safe - model of social relationships - divorce/separation (neg effective if there is no resolution of the conflict between parents) - adoption should be discussed openly Child abuse (phys and emotin) - neg effect on development Hostpitalization - regression of behavior/ development (not permanent- resolves within weeks of discharge) Death and dying - response depends on age and level of understanding - children should be included in grieving Birth order and child spacing

After an acute MI of LV free wall- which finding would most likely be seen in the LV two months later?

Fibrous scar NOTE: normal healing 6-8 weeks for MI (so you would expect necrosis to be replaced by scar within this time)

Flocculation tests

Flocculation occurs when the antigen is particulate Common test using this method= RPR (rapid plasma reagin) or VDRL (venereal disease reserach laboratory) screening test for syphilis caused by Treponema pallidum Postiive test shows appearance of "grains" on the test slide - VDRL and RPR tests are non-specific bc they detect non-treponemal antibody - They must be confirmed with a specific test such as the fluorescent treponema antibody absorption test (FTA-ABS)

Cetrimide agar

For isolation of pseudomonas aeruginosa - Cetrimide is a detergent that inhibits most bacteria except pseudomonads - Contains magnesium and potassium which promot the production of the pigments pyocyanin (blue-green) and fluorecein (yellow-green) produced by some pseudomonas spp, such as P. aeruginosa

Staph Epidermidis

Gram + coccus of normal skin microbiota --> would grow in the presence of NaCl (skin is salty)

Targets for Mutations

Growth-promoting proto-oncogenes - proto-oncogenes--> synthesis of oncoproteins- "gain-of-function" mutations (self-sufficiency in growth-promoting signals) Growth inhibiting tumor-suppressor genes - "loss-of-function" mutations (insensitivity to growth-inhibiting signals) Genes that regulate apoptosis - "loss of function" of proapoptotic genes --> evasion of apoptosis - "gain of function" of antiapoptotic genes--> evasion of apoptosis DNA repair genes - Insufficiency in DNA repair genes--> genomic instability Epigenetic mechanisms - DNA hypermethylation and hypomethylation - hypermethylation of promoters for tumor-suppressor genes--> silencing of tumor-suppressor genes - hypomethylation--> activation of protooncogenes - Histone acetylationn and deactylation Other mechanisms of Neoplastic Growth: - limitless replication potential (immortality) - sustaiined angiogenesis - ability to invade and metastasize - altered cellular metabolism (Warburg effect) - cancer-promoting inflammation* - ability to evade the host immune response* *= responses of the immune system

Examples of Abnormal protein accumulation

Hyaline: amorphous homogenous eosinophilic material (with H+E staining) - From Greek "hyalos"- crystal, glass - Intracellular hyaline: Russell bodies, Mallorry bodies, alpha1-antitrypsin granules/globules - Extracellular hyaline: hyaline arteriosclerosis and hyaline membrnae disease Amyloid: amorphous homogenous eosinophilic material (with H+E staining) - From latin "amylum"- starch (+iodine--> brown color) - built of abnormally folded protein - accumulates extracellularly

Differentiate between Hypoxia and ischemia

Hypoxia= a reduction in amount of O2 available to tissues Causes of hypoxia: - Ischemia: a reduction in blood flow to tissues - Reduced oxygen-carrying capacity of the blood: anemia or carbon monoxide poisoning - Ventilation defects: respiratory distress syndrome - Perfusion defects: interstitial lung fibrosis

What types of things influence fungal pathogenesis?

Immune system plays an important role in whether we get sick or not from our exposures - cell-mediated immunity is most important for most funal infections - neutropenia is a predisposing factor for invasic aspergilliosis Dose of exposure also influences

Russell Bodies

Immunoglobulin-containing globules within the cytoplasm of PLASMA CELLS Etiology: multiple myeloma and chronic inflammation **A type of intracellular hyaline accumulation

Aspirin toxicity

In acute aspirin poisoning, the first symptoms are usually: nausea and vomiting, rapid or deep breathing, tinnitus, sweating - high, therapeutic levels cause respiratory alkalosis (stimulates respiration) - toxicity causes mixed respiratory alkalosis and metabolic acidosis: hyperpnea, hyperthermia (uncoupling of oxidative phosphorylation) Treatment of aspirin overdose: Alkalinization of the urine increases the rate of excretion of free salicylate and its water-soluble conjugates

What are some causes and examples of physiologic hyperplasia (Increase in cell amount)?

Increased hormonal stimulation - proliferation of glandular epithelium of the female breast during pregnancy and puberty (breast hyperplasia in pregnancy) - less cells and increased stroma - Gravid uterus: smooth muscle cell hyperplasia (together with smooth muscle hypertrophy)

What is the smallest transposable element (most simple form of transposon)?

Insertion sequence (IS) - encodes transposase (tnp) and perhaps regulatory protein - flanked by inverted repeats (facilitates transposase binding and insertion into new site) - possess terminators and stop codons- inactivates the genes into which it is inserted; cell might die Non-composite vs. Composite transposons: - Non-composite transposons are insertion sequences with genes inserted into the IS - Composite transposons consist of two IS carrying other genes between them (possible to carry antibiotic resistance genes and genes can be added to the element) * these allow transfer of phenotype

List and describe some special parenteral routes of drug administration

Intrathecal: BBB trypically delays or prevents absorption of drugs into the CNS. It may be necessary to introduce drugs directly into the cerebrospinal fluid Intraarterial: used to localize the effects of drugs in a particular tissue or organ by delaying their systemic distribution Intracardiac: sometimes used in cardiac emergencies Intrapleural, intraperitoneal: used to localize the effect of a drug at a specific site by reducing the systemic absorption

What are the mechanisms of ATP depletion ( a mechanism of cell injury and necrosis)?

Ischemia affects the mitochondria thus decreasing oxidative phosphorylation which reduces ATP levels- reduction in ATP can lead to the following: - Insufficiency of ATP-dependent Na+ pump--> gain of Na+ --> gain of water--> swelling of mitochondria, ER, and cytosol - Cytoskeleton damange--> loss of microvilli and formation of blebs - Activation of anaerobic glycolysis --> depletion of glycogen stores and accumulation of lactic acid --> low intracellular pH --> clumping of nuclear chromatin - Detachment of ribosomes from rER and dissociation of polysomes into monosomes --> reduction in protein synthesis

KD vs Bmax

KD= concentration at which 50% of available receptors are bound by drug Bmax= maximum receptor binding that can be attained

After a gram stain you find that a bacteria is gram-positive bacilli, non endospore forming and a facultative anaerobe- what bacteria could it be

Listeria - will grow at low temperature (as low as 2*C - facultative intracellular, also facultative anaerobe (prefers aerobic - distinctive tumbiling motility in broth

What type of vaccine is polio, Sabin- Live-attenuated

Live (oral polio vaccine= OPV, Sabin vaccine) - Should be given to children

Compare and Contrast Live vs. Inactivated Vaccines ( Both two types of active immunization)

Live: - Given natural (orally) or via injection - low dose of virus - single dose (a booster may be req after 6-10 yrs)/low amount - no adjuvant needed - long-term immunity - IgG/IgA antibody response (if oral) - good cell-mediated immune response - Heat labile in tropics - occasional interference from other viruses or diseases - occasional mild sxs (esp. measles and rubella) - rare reversion to virulence Inactived: - Given via injection - High dose of virus - multiple doses needed/ high amt - needs an adjuvant (alum inefficient) - short-term immunity - IgG antibody response - poor cell-mediated immune response - no heat lability in tropics - no interference from other viruses or dises - occasional sore arm - no reversion to virulence

Immunodeficiency-Associated Cancers include

Lymphomas, both B-cell non-Hodgkin lymphoma and Hodgkin lymphoma - EBV infection Kaposi sarcoma - HHV8 infection Uterine cervix carcinoma - HPV 16, 18, etc. Etc.

CD markers ex. CD20 are markers for

Lymphomas/leukemias

Cocaine

MOA: - Blockage of reuptake of monoamines (NE, dopamine and serotonin) both in the central and peripheral NS by blocking the respective transporters- blocks NE transporter (NET) in the sympathetic NS - Inhibits voltage-gated Na+ channels Pharmacodynamics: - local anesthetic effect (blockade of Na+ channels- block initiation of action potentials) - peripheral effects are very close to those of NE - central effects are similar to those of amphetamines but shorter-lasting and more intense

Clinical uses for Beta-Antagonists

Main clinical uses: - Hypertension - Cardiac arrhythmias - Exertional angina Other clinical uses: - open angle glaucoma - pheochromocytoma (after treatment initiated with an alpha receptor blocker- why?) - hyperthyroidism- sx management - acute MI (may limit infarct size and prevent ventricular fibrillation) - Chronic coronary insufficiency (reinfarction prevention) - Hypertrophic cardiomyopathy (decreased heart efficiency) - ** Chronic heart failure (they counteract the activation of the symp. system, inhibit renin secretion and upregulate beta-adrenoreceptors)- contraindicated in acute heart failure - Tremor (essential, or due to drugs or anxiety states) - Migraine headache (mechanism unknown)- Propranolol - Prevention of esophageal varices (by blocking beta2-adrenoreceptors in liver) - Performance anxiety

What are some examples of generalized pathologic atrophy?

Marasmus: severe protein-caloric deficiency Cachexia: muscular wasting - TNF release in patients with cancer and chronic infectious diseses (ex. TB) - Cachexia is associated with cancer tissue

MALDI-TOF

Matrix-assisted laser desorption/ionization-time of flight mass spectrometry - measures exact masses of numerous proteins - produces a protein "fingerprint" for each organism - can identify isolated, cultured organisms quickly

After a gram stain you find the bacteria is a gram-negative bacilli with straight rods a facultative anaerobe that is oxidase negative- next you find it is lactose non-fermenting (ShYPS)- what test should you run next?

Non-H2S-producing (Shigella or Yersinia) vs. H2S- producing (Proteus or Salmonella) Non-H2S producing: Shigella: - non-motile - urease (-) Yersinia: - bipolar staining - slower growing than others, can grow <4*C - coagulase (+/-) - urease (+/-) - motility (+/-) H2S-producing: Proteus - swarming motility - urease (+) Salmonella - motile - urease (-)

What do the O, K, H antigen signify?

O antigen- LPS K antigen- capsule H antigen- flagella

M3 effects on organs

Parasympathetic - Contractions of smooth muscle in lung, GI tract, Bladder, detrusor - Relax sphincters in GI and bladder, detrusor - Increases secretion in GI - Erection in penis

Host-pathogen interactions

Pathogen: a microrganism capable of producing pathology (disease) Pathogenicity: ability to cause disease Infection: invasion of the host by microorganisms which may or may not lead to disease Virulence: A quantitative measure of pathogenesis - ID50 infectious dose: number of organisms (or amount of toxin) required to produce an infection in 50% of the test animals) - LD50 lethal dose: number of microorganisms (or amount of a toxin) required to kill 50% of the test animals Virulence factor: Microbial product that permit a pathogen to cause disease

What is the vector for Leishmania?

Phlebotomus sand fly Causes 3 basic forms of disease: 1. Leishmania tropica: dermal/cutaneous form (mildest) 2. Leishmania brasiliensis: mucocutaneous form 3. Leishmania donovanii: visceral form (most severe) **NOTE: amastigotes are found within macrophages in all forms of the disease

Glucocorticoids (steroids) ex. prednisolone inhibit

Phospholipase A2

Which NSAID has a long half-life (apprx 50 hrs) which allows for once daily dosing?

Piroxicam

Differentiate between 2 different isolation techniques

Positive pressure provides protective isolation for non-infectious, at-risk pts (i.e. pt with kidney transplant or 3rd degree burns) - increase pressure in room, air goes out when open- protects ppl inside Negative pressure provides sources isolation for infectious pts (i.e. pt with Measles bc transmitted by aerosols) - pt in room dangerous- air sucks in when opened NOTE: most rooms will be labeled with "Droplet Precautions" - green sign--> hand hygeien before barrier equipemtn - mask with shield and gown when working within 3 ft of pt, gloves at all times, remove in reverse order- hand hygeiene after removing barrier equipment - visitors: on first visit consult nurse before entering

Describe the phenotype change in cells stressed (infected) by virus

Pre-infection: - normal MHC-I expression - low IFNalpha/beta/gamma & IFNAR expression - low FAS expression Post-infection: - decreased MHC-I prior to CD8 activation--> NK cell recognition - high MHC-I-like expression (MIC-A/MIC-B, HLA-E) --> NK cell recognition - Then increased after CD8 activation --> CTL recognition - High Fas expression - High IFN-alpha/beta/gamma & IFNAR expression--> antiviral state - High Pkr expression--> antiviral state - HIgh 2',5' OAS/Rnase L expression --> antiviral state

Non-lactose fermenting Enterobacteriaceae that are H2S producing

Proteus - swarming motilit - urease positive - cause of UTI, kidney stones Salmonella - motile - important cause of gastroenteritis, systemic infection, and enteric fever "the PS in CEEK SYPS"

Ascaris Lumbricoides

Roundworm One of the MOST common human infections world wide! Mode: ingestion of eggs (food, raw vegetables i.e. lettuce) Site: adult in the intestine Diagnosis: large thick-walled eggs in feces *** Be able to recognize its eggs that are seen in feces

Antimuscarinic Drugs Clinical Use Summary

Scopolamine: given IM, IV, ophthalmic and transdermal patch* - prevent motion sickness* - preoperative; sedation and antiemetic - induce cycloplegia and mydriasis Solifenacin: given orally - treat overactive bladder/urge incontinence Glycopyrrolate: given oral, IM, IV, oral inhalational and topical - treat axillary hyperhidrosis (excessive sweating) - COPD - treat chronic drooling - reduce secretions during anesthesia - reversal of bradycardia - reversal of muscarinic effect of cholinergic agents used for neuromuscular blockade reversal Ipratropium: given nasal and oral inhalation - treat rhinorrhea (runny nose) - COPD

Hektoen Enteric Agar

Selective and differential for isolation of enteric pathogens - bile salts and indicator dyes inhibit the growth of gram-positive organisms Sugars: lactose, sucrose, and salicin - fermenters= yellow-pink, orange - non-fermenters= green or transparent Organisms that produce H2S will form a black percipitate (FeS) on the colony Diiferentiation of Salmonella and Shigella (salmonella is way darker on the plate)

Theta replication is used by most bacteria and plasmids, also some phages- BUT most phages use what kind of replication?

Sigma or Rolling circle replication * NOTE: also conjugative plasmids use this - Liner DNA molecule is generated through a nick Steps: - A nuclease makes a cut yielding a 3'-OH group and 5'-P group - Nucleotides are added to the 3'-OH group, displacing the 5'-P-terminated strand - Elongation of the 3' end continues - 5'-P-terminates strand is also copied

Role of Epigeneit cchnages in Carcinogenesis include

Silencing of growth-inhibiting genes via promoter hypermethylation Promoter Hypermethylation - Genes affected: tumor-supressor genes or DNA repair genes - DNA sequence does not chnage - Methylation of CpG islands of DNA Ex: - p16/INK4A gene in familial melanoma and colon carcinoma - BRCA1 gene in breast and ovarian carcinoma Activation of proto-oncogenes via hypomethylation--> chromosome instability--> biallelic expression (loss of genetic imprinting) Histone acetylation and deacytlation

Case Reports

Singl case - exposure(s) are included in the history - report of a UNIQUE clinical presentation - detailed description of the disease - NO comparison to non-diseased or unexposed - Statistical test: NONE Ex. Rare genetic disorders; first pts of an epidemic (i.e. HIV)

Streptococcus spp.

Some members of the genus are part of normal human flora while others are important human pathogens Ex of infections: Facial erysipelas, Impetigo, Streptococcal pharyngitis Streptococcus spp. are: - Gram positive cocci in pairs or chains - Catalase negative Species can be identified by: - Hemolysis patterns - Lancefield antibodies to cell wall carbohydrates - Antibiotic resistance Streptococci/Enterococci (Anaerobes) can be: Alpha hemolytic: - S. pneumoniae - Viridans streptococcis Beta hemolytic: - S. pygoenes - S. agalactiae Non-hemolytic (gamma): - Enterococcus - Some other strep

Beta3 effects on organs

Sympathetic - relax smooth muscle in bladder, detrusor - increase lipolysis in fat cells

Calcitonin is a marker for

Thyroid medullay carcinoma

T or F: Multiple Ribosomes may bind to a single mRNA

True! This allows for rapid production of protein

Indirect Acting Adrenergic Agonists

- Cocaine - Amphetamine - Methyldopa - Tyramine

List the steps in a Gram stain

1. Crystal violet: stains both Gram+ and Gram- 2. Iodine: complexes form to retain stain 3. Alcohol decolorizer: lipids washed away, peptidoglycan remains (lipids are richest in gram -, gram+ retain stain bc thick PG layer) 4. Safranin: counterstain is visible in decolorized cells (to prove gram negative is there (stains reddish pink))

In Binary fission, during the exponential phase, growth is by a

geometeric progression - 2^0, 2^1, 2^2.... 2^n (n=# of generations) - Very large number of cells very fast (1>2>4>8>16)

What are some immune evasion strategies of pathogens?

- Bacterial toxins work by distinct mechanisms - Some exported out of cell and some are directly injected - Many target host immune cells Bacteria have toxins that can: A. Damage membranes (pore forming toxins) B. Cleave host surface components C. Modulate signal transduction pathways D. Protein synthesis inhibitors

What are some subcellular changes seen in atrophy?

- Decreased numbers of organelles - An increase in autophagic vacuoles - Lipofuscin accumulation --> brown atrophy (myocardium becomes brown- lipofuscinosis)

List 5 types of Adaptive Responses

- Hypertrophy: cells increase in size (both physiologic and pathologic) - Hyperplasia: cells increase in number (i.e. enlarged lymph nodes)- both physiologic and pathologic - Atrophy: reduction in number and size (both physiologic and pathologic) - Metaplasia: changes types (i.e. Barretts esophagus)- both physiologic and pathologic - Dysplasia: never normal, ONLY pathologic

A common cause of persistent infections includes

Bacterial Biofilms: which are a collection of aggregated bacteria bound to a surface and embedded in self-produced polymeric matrix Why do bacteria form biofilms? - Bacteria within biofilms are inherently resistant to antimibrobial agents: phagocytic cells, antibiotics, ROS, chemical agents Example of clinically important biofilm: Dental caries - Biofilm --> sugars from diet provide nutrients for bacteria --> acid --> damage to enamel --> inflammation --> tooth decay --> biofilm

KD is a measure of affinity- if the druf has high affinity

KD will be a low value; if the drug has low affinity then KD will be a large value

Enzyme regulation involves the increased or decreased synthesis of a

second messenger (the most common post receptor mechanism) - Almost all second messenger signaling involves phosphorylation or dephosphorylation of protein substrates - Ion channel regulation involves opening or closing the channel - Many receptors (ex. steroid) affect gene transcription

EC50 is the concentration of drug that produces

50% of the maximum efect of that drug

____ are surface components that can mediate motility towards a surface and dissemination

Flagella - Directional motility mediated by the flagellum is called CHEMOTAXIS - Swimming motility occurs in liquid and semisolid environments E. coli are about 1 micrometer in diameter by 2 micrometers long and swim at about 30micrometers/second In human terms, this is 15x ~6ft= 90ft/sec or ~60miles/hr

Compare and Contrast Metaplasia vs. Dysplasia

Metaplasia - Replacement of one adult cell type with another adult cell type of the same germ layer - Mature tissue - Reversible - May create a background for neoplastic transformation, aka may progress to dysplasia Dysplasia: - Expansion of immature epithelial cells - Synonym= Intraepithelial neoplasia - Disordered proliferation of immature cells with features of pleomorphism - Reversible - Is a preneoplastic condition, with much higher risk of malignant transformation than metaplasia

If you treat cells with epinephrine, how much cAMP will be produced?

- Depends on how many beta-2 receptors are activated (and Gs, adenylyl cyclase) - Depends on how much epinephrine you add Concentration-effect curve: Epinephrince concentration (nM) vs. cAMP produced (%max) --> yields hyperbolic curve on linear scale - Emax= Max cAMP produced by epinephrine acting on Beta2 receptor - EC50= Effective concentration 50%- how much epinephrine is required to produce 50% of max cAMP Plotting same thing on logarithmic scale (increase epinephrine concentration by factors of 10)--> yields a sigmoidal curve, no longer hyperbolic

What are some subcellular changes that occur in hypertrophy (increase in cell size)?

- Increased in size nulceus due to increased DNA content (nuclear hypertrophy) - Increased synthesis of mRNA and rRNA - Hypertrophy and hyperplasia of endoplasmic reticulum, golgi apparatus, and mitochondria - Activated protein synthesis NOTE: Cardiac hypertrophy: we see thicker fibers, bigger nucleus and sometimes Boxcar nucleus in rectangular shape which in cross section have a bizarre shape

What are the colors that hyphae can take?

Dematiaceous- dark - in case of Black mold - If you have pt with respiratory symptoms and a dark stain in her bathroom this is a bad sign= presence of mold Hyaline- colorless - or brightly pigmented because of stain to make it visible

Describe Hyphal growth

Hyphae grow at the tips- Apical growth - this is why you sample lesions at outer margins to see best fungi- fungi in the middle are already usually dead

Immune evasion strategies of pathogens include:

Stealth: - Hide: capsules, biofilms - Rub: antigenic variation, modify surface - "just fit in": molecular mimicry Frontal attack: - Kill: toxins - Disarm: toxins, proteases, peptidase - Invade

Giemsa stain can be used to identify

Thick blood smears or bone marrow for suspected Histoplasma with Giemsa stain Other stains commonly used: - Fluorescent antibody staining: available for a few of the systemic fungi

What are the most common portals of entry for pathogenic microorganisms?

a. Respiratory tract - Ex. Streptococcus pneumoniae, Bordetella pertussis b. Gastrointestinal tract - Salmonella, E. coli, Vibrio cholerae c. Skin and mucous membranes - Staphylococcus aureus, steptococci d. Genitourinary tract - Neisseria gonorrheae, Chlamydia e. Direct inoculation: - Insect borne (vector), Ex. Rickettsia - Opportunistic: Ex. Surgery or indwelling device - Cuts and scrapes - Fomites

A better way to classify infections is by the

degree of host damage Host- Microbe contact --> Infection--> A. Acquisition followed by elimination (physical defenses or immunity) B. Acquisition may result in damage and disease in certain hosts C. Commensal microbes can cause disease if commensalism is disturbed by immune impairment or alterations in host microbial flora D. Colonization may be terminated by an immune response E. Colonization may lead to disease if sufficient damage ensues F. Colonization may lead to a state of persistence (immune response not able to eradicate infection) G. An immune response or therapy may eradicate the infection but damage may be irreversible H. If sufficient damage is incurred death may result I. Persistent infections may reactivate and cause overt disease

At high concentrations, the full agonist will have an effect that

saturates as the maximum effect that the system can produce. Emax is that maximum effect that the drug can produce. For a full agonist, Emax equals the maximum effect that the system can produce. Receptor binding will saturate at Bmax, when all available receptors are bound by the agonist

Apoptosis

"Programmed" death genetically controlled by enzymatic pathways Morphologic hallmark: formation of apoptotic bodies: round-oval masses of intensely eosinophilic cytoplasm containing dense nuclear fragments Physiologic causes: - destructions of cells during embryogenesis - hormone-dependent involution in adults (endometrial breakdown in menstrution and lactating breast after waning) - cell depletion in epidermis and intestine - negative selection of T-lymphocytes in the developing thymus Pathologic causes: - DNA damage induced by radiation, cytotoxic drugs, and hypoxia: via TP53 activation - Accumulatin of misfolded proteins: neurodegenerative diseases ex. Alzheimer - Interaction with cytotoxic T-lymphocytes: viral infection, ex. viral hepatitis; transplant rejection - Pathologic atrophy after duct obstruction, ex. pancreas or kidney

What is a chemical antagonist?

"antagonist" physically binds to the "agonist" and prevents "agonist" from having its effect Ex1: antacids are used to prevent the actions of stomach acid Ex2: heavy metal toxicity is treated with a drug to chelate the heavy metal and prevent its toxic actions Ex3: protamine sulfate is positively charged and is used to treat toxicity due to the anticoagulant heparin (which is negatively charged)

What vaccine should be received for Bordetella pertussis (pertussis/whooping cough) - 2 types: wP and TDaP

(1) Inactivated (whole-cell), adjuv. (2) Acellular (pertussis toxoid w. or w/o B. pertussis components such as filamentous haemagglutinin, fimbiral antigens, and pertactin Should be recieved by: (1) Children (2) to Children, adolescents, and adults and pregnant women

Mallory Bodies

Distinct eosinophilic granules in the cytoplasm of hepatocytes Content: intermediate cytokeratin filaments Etiology: alcoholic liver disease **A type of intracellular hyaline accumulation

Properties of Herpesviruses

- Express many enzymes involved in nucleic acid metabolism, DNA synthesis, and processing proteins - Gene transcripiton, DNA synthesis, and nucleocapsid assembly occur in the NUCLEUS*** - Lytic infection is usually associated with cell destruction** - Infect cells latently (lifelong infection) with reactivation potential**, although no general common strategies are apparent (i.e. different viruses establish latency by diff. mechanisms

When providing medical results or info which may cause distress to pt..

- Find out how much the pt knows - Be honest: "I am sorry, but the news is not good" - Find out how much the pt wants to know - Give the news in simple clear terms - Show empathy - Offer support and guidance

What are some approved treatments for cytomegalovirus (CMV) infections in immunosuppressed pts?

- Ganciclovir: inhibits viral DNA polymeras and causes DNA termination (can treate severe infectiona) - Valganciclovir (better bioavailability than ganciclovir) - Cidofovir: does not req. a viral enzyme for activation - Foscarnet: inhibits viral DNA polymerase by mimicking the pyrophosphate portion of nucleotide triphosphates - Use of condoms and absitnence - Screening of potential blood and organ donors for CMV seronegativity (esp for blood to be given to infants) **Seropositive mother is least likely to produce a bby with symptomatic CMV disease NO vaccine for CMV is available

beta1 receptor

- Heart --> increases force and rate of contraction - Kidney; juxtaglomerular cells--> increases renin release

For a sputum culture growing streptococcus pneumoniae- the clearance of these organisms from lung parenchyma would be most effectively accomplished through generation of which substances?

- Hypochlorite (hypochlorous acid)- MOST potent - Hydrogen peroxide could also kill--this is compromised in chronic granulomatous disease- NADPH deficiency

What types of substances can accumulate?

- Normal cellular consituents: water, lipids, proteins, and carbohydrates - Pigments: lipofuscin, melanin, bilirubin, carbon particles, and tattoo ink - Abnormal proteinaceous substances: hyaline, amyloid - Minerals: iron, copper, and calcium

Gram positive streptococci

- S. pyogenes - S. agalactiae - S. pneumoniae - E. faecalis, E. faecium - Viridan group streptococci

D1 receptor

- Smooth muscle --> dilates renal blood vessels

Mycoplasma DO NOT gram stain- describe them

- extracellular - very small - lack a cell wall - pleomorphic - require sterols - sensitive to environment - extremely fastidious - tiny "fried-egg" colonies on agar

Describe the pharmacogenetics of the CYP450 enzyme

A specific gene encodes each CYP450 enzyme- P450 enzymes therefore exhibit considerable genetic variability among individuals and racial groups - Some persons may be classified as "poor metabolizers" or even "ultra rapid" metabolizers Ex: Some persons are poor metabolizers of CYP2D6, which metabolizes many beta blockers, antidepressants, and opiods Standard drug doses may cause adverse effects related to elevated drug serum levels if a person is a poor metabolizer (the opp will occur for rapid metabolizers) Ex: Acetylation is a phase 2 reaction (metabolism). It is catalyzed by N-acetyltransferase, an enzyme which is under genetic control. About one-half of ppl of caucasian origin are slow acetylators, since they have a deficiency of the enzyme, inherited as an autosomal recessive trait

Tumor Progression

A tumor is formed by the clonal expansion of a single mutated precursor cell - Carcinogenesis results from the accumulation of complementary mutations in a stepwise fashion - Once establised, tumor evolved genetically during its outgrowth and progression (Darwinian selection, i.e "survival of the fittest) --> selection of the fittest explains the natural history of cancer and tumor behavior following therapy NOTE: one cell becomes the initiating cancer cell

All signals from the CNS use

Acetylcholine Peripheral Efferent Nervous System: - All preganglionic neurons are cholinergic (use acetylcholine) - All parasympathetic neurons (pre and postganglionic) use acetylcholine) - The neurons of the somatic nervous system use acetylcholine - Sympathetic neruons to the sweat glands use acetylcholine - Receptors activated by acetylcholine are used for signaling in every branch of the peripheral nervous system ** remember to consider the somatic nervous system when we talk about cholinergic drugs

List the Adrenoreceptor signal transduction

Alpha1 (Gq): increases IP3 and DAG, increases Ca2_ Alpha2 (Gi): decreases cAMP/opening of K+ channels Beta1 (Gs): increased cAMP, Open Ca2_ channels in cardiac cell membrnaes Beta2 (Gs): increases cAMP, decreased Ca2_ Beta2 (Gs): increases cAMP D1 (Gs): increases cAMP D2 (Gi): decreases cAMP/Opening of K+ channels

Drug carcinogenesis

Anticancer durgs and alcohol have known carcinogenic activity - Effects of carcinogens are dose-dependent, additive and irreversible - there is always a long latent period between exposure to the agent that causes tumors and the detection of cancer - Most cancer-causing chemicals are prob not carcinogenic in the form in which they enter the body but are metabolically activated into reactive intermediates that are toxic and carcinogenic (epoxides, nitrosamines, etc)

Occupational Carcinogens

Arsenic & compounds --> Can cause skin, bladder, lung carcinoma, Liver hemangiosarcoma (from metal smelting; alloys; drugs; herbicides) Asbestos--> Can cause mesothelioma and lung carcinoma (from heat insulation; roofing paper; floor tiles) Benzene--> Can cause Leukemia (from Light soil; solvent; fumigant) 2-(or Beta)- Naphthylamine--> can cause Bladder carcinoma (from the rubber industry) Vinyl Chloride--> can cause liver hemangiosarcoma (from Refrigerant; monomaer of PVC) Metals, Metalloid and Their Compounds which can cause Lung carcinoma: - Beryllium (from electric switches, jets, and rocket engines) - Cadmium (from yellow pigments; batteries- this can also cause prostate and renal carcinoma**) - Chromium (from alloys; pigments) - Nickel (from plating; alloys; ceramics; batteries) - Radon (from product of uranium decay; found in quarries and mines)

Insufficiency in Homologous Recombination repair can lead to

BRCA1 and BRCA2 Mutations Germline BRCA1 mutation: - Familial breast cancer in women - Very high risk of ovarian carcinoma Germline BRCA2 mutation: - Familial breast cancer in women - High risk of ovarian carcinoma - Breast cancer in men - Prostate, pancrease, bild duct, stomach cancer

After a gram stain you find that the bacteria is gram-negative bacilli, coccobacilli/pleomorphs (most non-motile) and an anaerobe- which bacteria may it be

Bacteroides, Prevotella or Porphyromonas Bacteroides: - pleomorphis - stain poorly - easy to grow - normal GI, oral flora - a few species motile Prevotella: - very small - slow growing, fastidious - normal oral flora (bites) - black colonies on BAP Porphyromonas: - very small - slow growing, fastidious - normal oral flora - black colonies on BAP

Cell wall synthesis inhibitors (antibacterial drugs)

Beta lactams: - Penicillin - Cephalosporins - Carbapenems - Monobactams Others: - Vancomycin - Fosfomycin

What structural changes of reversible injury can be viewed via light microscopy (LM) rather than electron microscopy (EM)?

Cellular swelling (syn: hydrophobis change or vacuolar degeneration) - small clear vacuoles within the cytoplasm (distended cisterns of ER) - cytoplasmic clumping - cell enlargement (detected by diminished in size extracellular compartments: stroma, blood capillaries, lymphatics, lumina of ducts, etc.) Fatty change (a component of cell injury) - small clear vacuoles (lipid droplets)

Incidence and Mortality of the Most common cancers in US

Cancer Incidence: Males: - prostate- 24% - Lungs and bronchi- 14% - Colon and rectum- 8% Females: - Breast: 29% - Lungs and bronchi- 13% - Colon and rectum- 8% Cancer Mortality: Males - lungs and bronchi- 28% - prostate- 10% - colon and rectum- 8% Females - lungs and bronchi- 26% - breast- 15% - colong and rectum- 9%

Warburg Effect

Cancerous cells utilize glucose via aerobic glycolysis: one glucose molecule--> two pyruvate and two ATP molecules - pyruvate is later utilized in metabolism Warburg effect is used in positron emission tomography (PET) scanning - "Glucose-hungry" neoplastic cells take 18F-fluorodeoxyglucose (a nonmetabolizable derivative of glucose) at the higher level, if compare with normal cells)

OARS: Eliciting Change Talk

Change talk: an indication that you are successfully using motivational interviewing If you are using MI successfully, you will hear statement that indicate the pt: - recognises the disadvantages of staying the same - recognises the advantages of change - expresses optimism about change - expresses the intention to change How to elicit change talk: - Directing: close-ended questions - Guiding: specific open-ended questions - Following: general open0ended questions or listening Ex: "Desribe the last time this happened.." "Give me an example of that.." "Tell me more about that.." "Imagine the worst consequences of not changing and the best consequences of changing" "What are the most important things in your life?"

A pt with infective endocarditis- has a section of the adrenal cortex with loss of nuclei, but preserved cellular outlines- this is referred to as

Coagulative necrosis

CA 19-9 is a marker for

Colon and pancreatic carcinoma

Acting out

Deal with emotional conflict or internal or external stressors by actions rather than reflections or feelings. Defensive acting out is not synonymous with bad behavior bc it req. evidence that the behavior is related to emotional conflicts

If a cervical biopsy demonstrates DISORDERED maturation of squamous epithelium, with hyperchromatic and pleomorphic nuclei extending the full thickness of eptihelial surface- this disorganization can be referred to as

Dysplasia - "if it is in ALL layers "full thickness'"= severe dysplasia - full thickness is 3 thirds of epithelium effected

Pigment Accumulation

Endogenous pigments: - Lipofuscin - Melanin - Bilirubin - Hemosiderin Exogenous pigments: - Carbon/coal dust - Tattoo ink: carbon, titanium dioxide, and other pigments

Non-hemolytic streptococci

Enterococcus - Share growth characteristics with streptococci - Lancefield Group D antigen positive - Resistant to bile salts (will grow on bile esculin agar, impt. species will hydrolyze esculin- looks like black precipitate on bile esculin agar) - part of normal GI flora - seldom cause disease in healthy individuals (opportunist) - E. faecium and E. faecalis most important species - Frequent cause of nosocomial infections - Highly resistant to environmental and chemical agents - Antibiotic resistance is a major problem

What are the cardiovascular effects after Epinephrine IV infusion?

Epinephrine works on Beta1=Beta2=Alpha1 (beta2 has most affect) Increase in: - systolic BP (Beta1) - MAP - Direct effect HR (beta1) - Final effect on HR (beta1 strong effect) Decrease in - diastolic BP (Beta2 effect) - reflex effect on HR ** this is dose dependent can be increase, decreased or zero

Describe the cardiovascular effects of endogenous agonists

Epinephrine: beta1=beta2=alpha1 Norepinephrine: alpha1=beta1 Dopamine: D1>>Beta1>>Alpha1 * These molecules are used as drugs, but they occur naturally in the body * They do NOT cross the BBB: they are very poler and will stay in the periphery --> no brain involvement when using these drugs

Tellurite agar (cystine-tellurite agar)

For isolation of Corynebacterium diphtheriae - Potassium tellurit inhibits gram-negative organisms and most upper respiratory flor except corynebacterium sppp. - C. diphtheriae colonies appear gray or black (due to tellurit reductase activity) with a brown halo (cysteinase activity) around the colonies

What are Teichoic and Lipoteichoic acids and where are they found?

Found in Gram-positives only They are polymers of negatively-charged sugars - anchored to different parts of the cell envelope - lipo- have lipid anchor They play a general role in regulation of autolysis Also fx as: - Ashesins (can stick) - PAMPs - other roles too!

H. Pylori can cause

Gastric adenocarcinoma of intestinal type via: Chronic inflammation--> atrophy of gastric mucosa--> intestinal metaplasia--> dysplasia --> carcinoma Mantle cell lymphoma via Chronic inflammation--> B-cell activation--> t(11;14) --> CCND1 overexpression--> polyclonal proliferation (hyperplasia)---> neoplastic transformation

Activation of alpha2 receptors leads to activation of the

Gi protein (blocks the activity of adenylyl cyclase which leads to decreased cAMP)

Staphylococcus spp.

Gram positive cocci in clusters, catalase (+) S. aureus is most important pathogen - Coagulase (+) - Beta-hemolytic - Yellow colonies (often) - Salt tolerant (haloduric/philic) - Produces acid from mannitol (yellowish) - if no acid on mannitol plate stays pink Coagulase-negative staphylococci (CoNS) - most are normal microbiota (less frequent, less severe than S. aureus; opportunists - dont ferment mannitol - S. saprophyticus and S. epidermis are important pathogens (can be differentiated by novobiocin susceptibility) --> S. epidermis has a zone of inhibition so it is sensitive to novibiocin while S. saprophyticus is not

List the diseases caused by HHV-1 - HHV-8

HHV-1/HHV-2: - Orolabial herpes (HHV-1>HHV-2) - Genital herpes (HHV-2>HHV-1) - Encephalitis - Disseminated infection (neonates) HHV-3: - Varicella or chickenpox - Zoster or shingles HHV-4: - Infectious mononucleosis - Burkitt lymphoma HHV-5: - Infectious mononucleosis - Cytomegalic inclusion disease (congenital) - Systemic disease (immunocompromised) - Pneumonitis (immunocompromised) - Retinitis (immunocompromised) - Encephalitis (immunocompromised) HHV-6 & HHV-7: - Roseola Infantum HHV-8: - Kaposi sarcoma

Reportable incidents

Health conditions (public concern)--> infectious diseases and non-infectious diseases --> report to state or local health department--> CDC Imminent Danger: - Child Abuse--> State/local child and family services - Suicide/Abuse - Intimate Partner Violence: NOT reportable- varies by case/state Adverse Events - Sentinel events--> TJC - Medical Errors--> Disclosure (pt), Notify (facility, other)

Describe the structure and function of flagellum in bacteria

Helical protein filament, anchored in membranes Made of flagellin subunits (protein subunits) - Called the "H" antigen in serotyping (ex. O157H7- is the E.coli causing foor borne outbreaks - refers to bacterium with LPS type 157 and flagellum serotype 7-- only bacterium have this notation) - Also a PAMP They have a variety of arrangements (can have single flagellum, or many flagellum) - Usually on rod/spiral shaped bacteria Major function: Motility ** Our host cells do NOT have flagella so this is something we can go and try to target

Pillars of Anti-viral Defenses

IFN-alpha/Beta IFN-gamma Cell-mediated immunity (Innate/Adaptive) Humoral immunity (Innate/Adaptive) ----- Innate immune defenses include Proinflammatory cytokines: IFNalpha/Beta and IFN-gamma (leads cells into an antiviral state: - produced by virally infected cells and immautre dendritic cells (rapid) - induced by dsRNA and long ssRNA (polycistronic RNA) - induces the death of infected cells, as well as bystander cells should they become infected Many different mechanisms induce apoptosis in infected cells 2 diff pathways to focus on include - Protein kinase PKR and Oligodenylate Synthetase OAS

What are some causes and examples of Pathologic hypertrophy (increase in cell size)?

Increase mechanical demand: - LV myocardium in hypertension - RV myocardium in chronic pulmonary diseases due to increased resistance in the pulmonary circle - Smooth muscles of the urinary bladder in benign prostate hyperplasia due to compression of the urethra Compensatory after removal of a paired organ: Ex: renal hypertrophy after nephrectomy (removal of one kidney makes the other larger)

What are some induced disease from the Epstein-Barr Virus (EBV)

Infectious Mononucleosis Burkitt lymphoma - EBV--> t(8;14) with C-MYC overexpression Nasopharyngeal carcinoma (common in adults) Hodgkin lymphoma Non-hodgkin B-cell lymphoma in immunocompromised pts

Human Herpesvirus 8

Kaposi Sarcoma-Associated Herpesvirus ** HHV-8 DNA sequences were discovered in biopsy specimens of Kaposi sarcoma, primary effusion lymphoma (a rare type of B-cell lymphoma) and multicentric Castleman disease through use of PCR analysis Kaposi Sarcoma: - one of chaacteristic opportunistic diseases associated with AIDS - virus is unique and a member of subfamily gammaherpesvirinae * Similar to EBV, B cell is primary target for HHV-8 BUT the virus also infects a limited number of endothelial cells, monocytes, and epithelial and sensory nerve cells IN the Kaposi sarcoma tumores--> endothelial spindle cells contain the virus

Which NSAID - provides better analgesia than other NSAIDs; acute pain (<5 days) - available intra-muscular, intravenous, nasal spry

Ketorolac

What are 3 types of cells and their adaptive potential

Labile cells - Include: epithelia, hemo- and lymphopoietic cells, spematogonia - Potential mitotic activity: continuously dividing (M--> G1) - Adaptive potential: multiply, but can NOT become larger** Stable cells (**MOST CELLS) - Include: glandular organs (liver, etc.), fibroblasts, smooth muscles - Potential mitotic activity: Usually in G0, but can enter cell cycle upon stimulation - Adaptive potential: can multiply and become larger Permanent cells - Include: Neurons, skeletal and cardiac muscles - Potential mitotic activity: unable to divide, permanently in G0 - Adaptive potential Can NOT multiply, but CAN become larger **

S100 is a marker for

Melanoma and neural tumors

MOA of Metronidazole

Metronidazole is a prodrug: - Anaerobic pathogens contain electron transport components (ferredoxins) which can donate electrons to metronidazole - The reduction of the nitro group of metronidazole within the microorgansim forms a highly rx nitro radical anion which breaks DNA strands ** Ultimate effect is bactericidal ** Increasing levels of oxygen inhibits the electron donation to metronidazole, reducing the formation of the highly reactive nitro radical- this explains why the drug is not active upon aerobic bacteria

Indirect Acting Antiadrenergic Drugs (inhibition of catecholamine synthesis)

Metyrosine

Defects in DNA repair systems

Mismatch (i.e. substitution)- defect with mismatch repair - Defects can lead to: Hereditary non-polyposis colon cancer syndrome (HNPCC or Lynch syndrome) Formation of pyrimidine dimers- defect with Nucleotide excision repair - Can lead to Xeroderma pigmentosum Double-strand DNA breaks- defect with homologous recombination repair Can lead to: - Ataxia-telangiectasia - Familial breast carcinoma (BRCA1 and BRCA2 associated) - Bloom syndrome - Fanconi anemia

Alpha1-Antitrypsin Deposits

Mutations in alpha1-antitrypsin--> abnormal folding --> accumulation of protein in rER--> formation of eosinophilic PAS (+) globules in periportal hepatocytes Diseases with alpha1-antitrypsin deficiency: - Liver cirrhosis - Pulmonary emphysema **A type of intracellular hyaline accumulation

Typical Fecal-Oral Life Cycle

Occurs mostly in areas of poor hygeine Trophozoite (found in diarrhetic meterial- they are fragile and die after a few minutes- go into feces Trophozoites are capable of: - feeding - motile - replication Trophozoites when feces are first soft)---dessication--> becomes cyst to be more resistant Cysts are: - usually passed in feces - resistant - infective After excystation the cyst becomes a trophozoite

Which cells must be found to confirm chronic inflammation?

Plasma cells

Differentiate between Proapoptotic, Antiapoptotic, Sensors (BH-3 only) and how they control mitochondrial pathway

Proapoptotic (BAX, BAK): allow leakage of cytochrome c into cytosol Antiapoptotic (BCL-2, BCL-XL, MCL1): Block BAX and BAK and prevent release of cytochrome c into cytosol Sensors (BH-3 only) (BAD, BIM, BID, Puma, Noxa): Sense cellular stress and damage, regulate balance between anti- and proapoptotic groups

Developmental Milestones

Purpose of reg. developmental screening: - identify and react to deve. delayds - provide anticipatory guidance: "what parent should expect" - most important in children with cerebral palsy to aboid dev. delay *** Well infomed parents are out best allies in diagnosing and managing developmental delays CDC: cut-off ages by which ALL children should achieve certain milston (if fail--> high likelihood of dev. pathology) - Avg age at which MOST children would achieve it ---- more sensitive (but less specific) so that there is increased awareness in monitoring this "at-risk children" "Gottat Find Strong Coffee Soon" - Gross motor - Fine Motor - Speech/lang - Cognitive/problem solving - Social/emotional ** CDC is always the most correct in the guidelines

Finding/Fixing Medical Errors

Rates= 3rd leading cause of death in US - must report to prevent recurrence - near-miss reports just as important as reporting actual mishap - most errors not reported bc fear/humilliation **Joint commission (TJC) mandates hospital report certain event types Sentinel events: defined by TJC - any unexpected occurence involving death or serious physical or phsycological injury, or the risk thereof - all accredited organizations must define sential event in establishing mech to identify, report and mange these When sentinel event occurs each org must: - conduct timely, credible root cause analysis - develop an action plan to reduce risk - implement the improvements - monitor the effectiveness of those improvements *** Goal of reporting is to find & fix root causes of medical errors rather than dealing with whack-a-mole phenomenon

Describe uncoating of a virus

Release into host cell of viral genomic NA(s)/accessory proteins by capside disassembly or NA injection Capsid protein conformational changes triggered by: - pH change - receptor binding Membrane removal via fusion Can occur: - at plasma membrane - within endosome - following endosomal escape - at the nuclear membrane * this is related to entry mechanism * neutralizing antibodies may interfere

List the dsRNA viruses

Reoviridae (naked) * this is RNA

Descrbe the replication of Gapped, or partially double stranded DNA viruses

Restricted to Hepatitis B virus (Hepadnaviridae) - First, the partially dsDNA must be repaired to generate bona fide dsDNA that can be used by cellular DNA-dep RNA pol (RNA pol II) --> this is achieved by cellular DNA repair system and some viral proteins (evidence shows the virus' reverse transcriptase is involved) - Once gaps in DNA have been filled, cellular DNA-dependent RNA polymerase can transcribe the DNA --> mRNA so that protein syn can occur - Proteins syn includ: a virus specific reverse transcriptase (diff from retroviral reverse transcriptase) is the one responsbile for reverse transcribing pre-genomic mRNA into gapped dsDNA - Both pre-genomic mRNA and the reverse transcriptase are encapsidated and reverse transcription of pre-genomic mRNA yields partly dsDNA

Mirabegron

Route of administration: oral MOA: Beta3 selective agonist ** (NO cardiovascular effect) Pharmacologic effect: Detrusor muscle relaxation and increased bladder capacity Clinical use: Incontinence: overactive bladder symptoms with frequency, urgency or urge urinary incontinence

Parasympathetic and Sympathetic actions

Saliva, mucus, feces, tears, muscus--> parasympathetic Sweat--> Sympathetic cholinergic

Radioimmunoassay

Similar to immunofluorescence EXCEPT uses a radioactive label instead of fluorescein * Very sensitive used to detect small amts of antibody Ex. IgE occurs in low conc in serum 2 forms of radioimmunoassy are used for IgE detection: - RIST (radio immuno sorbent test): for total IgE (not used clinically)- used if one would like to detemine level of serum IgE without reference to any specific antigen ** IgE levels may be elevated in certain parasitic infestations - RAST (radio allergo sorbent test): for SPECIFIC IgE- more clinically useful- gives level of serum IgE that specificially reacts with known antigen/allergen- provides evidence that a pt is indeed sensitized to the particular substance - test has been extensively modified over yrs and a fluorescence enzyme-based assay developed as replacement, ImmunoCAP is new FDA approved test

RNA viruses can be

Single-stranded I. Positive sense a. Naked: - picorna- - calici- - hepe- - astro- b. enveloped: - flavi- - retro- (diploid, iDNA) II. Negative sense a. Enveloped: - paramyxo- - delta- b. segmented or Double-stranded I. Segmented a. Naked - Reoviridae

What are the uses for PCR-based techniques?

Standard diagnosis for: - HPV - Chlamydia trachomatis & Neisseria gonorrhoear Routine for quantification of viral loads of: - HIV - HBV - HCV Regularly used in diagnosis of: - HSV, CMV, EBV, VZV - Tick-borne infections - Respiratory virus infections

If a drug targeted the parasymp NS which of the following is the most likely adverse effect ?

Sweating - Using M agonist --> increased saliation and decreases HR - Sweating is symp only - only symp using muscarninc receptors so it is a plausible side effect

Pharmacological effects of Beta-Nonselective (beta1beta2) and alpha1-antagonists

The additional blockade of alpha receptors by these drugs can cause: - marked decrease in total peripheral resistance (decrease BP- good for hypertension) - minimal changes in HR and CO (the marked decrease in total peripheral resistance causes reflex tachycardia, which is counteracted by the direct effect of beta1-blockade on heart rate

Signal transmission at an Adrenergic Synapse

The endogenous catecholamines dopamine, norepinephrine, and epinephrine are all synthesized from tyrosine - rate limiting step in catecholamine syn is conversion of tyrosine to Dopa, which is catalyzed by tyrosine hydroxylase - Dopa is converted to dopamina and transported into vesicles by the vesicular monoamina transporter (VMAT)- in adrenergic neurons dopamine is converted to norepinephrine - NE is released from vesicles when an AP opens voltage gated Ca2+ channels and triggers vesicle dusion with the plasma membrane - NE released into the synaptic cleft binds to receptors on postsynaptic and presynaptic neurons. NE binds to alpha and beta adrenoreceptors - When NE binds to alpha2 receptors on presynaptic vesicles, NE release is diminished (negative feedback) - NE is removed from the synapse by the NS transporter (NET) - once transported into the cytosol NE can be re-stored into vesicles or metabolized by monoamine oxidase (MAO)

Microbial Resistance to Glycylcyclines

Tigecycline - it was developed to overcome the recent emergence of tetracycline class-resistant organisms- However, resistance can occur and is primarily attributed to overexpression of multidrug efflux pump

What is a virus and how does it differ from other microbes?

Virus is a multi-component non-living infectious agent whose replication requires a host cell Viruses differ from other microbes because they CANNOT make energy or encoded proteins - metabolically inert (not living) - require living cells to replicate (obligate intracellular parasites) - components derived from host, often virally-encoded - assemble rather than divide - unaffected by antibacterials, antifungals and antiparasitics

Differntiate between virions vs. viruses

Virus= the entity ("the measles virus") the disease Virion= an infective, complete, and mature viral particle - delivers the viral genome to a susceptible and permissive cell or host - transmits the entity or disease - contains nucleic acid and protein (minimally) - up to 99% of viral particles created have an error

Examples of first words in a sentence and what they elicit

What? - facts and info How?- process and/or feelings Why?- reasons Could? Can? Would?- general framing or summary

Differntiate between wild type vs. Mutant

Wild type: description of a bacterium that is found MOST abundantly in nature "normal type" Mutant: bacterium that differs genetically from the wild type. The mutant has a genotype diff. from the wild type strain which may or may not result in readily observable trait (change in phenotype) ** Mutants arise by mutations- changes in gene sequences Mutations and selection are important in the natural evolution of bacteria (slow process) Normally: Gene X--> Protein X--> Cellular Function BUT Gene X--(gene mutation)-->Allelic variant of gene x--> Modified protein which can either have: - Normal function (common) - Reduced or loss of function (less common) - Enhanced function (rare) Then there is selection for the altered function of protein X - Then the bacteria with the altered function of protein X predominate in the population Ex: Mutations in a negative regulator (MucA- which usually prevents too much slime) results in high level synthesis of exopolysaccharide (slime) by Pseudomonas aeruginosa (*** this will not occur in healthy individuals but in those with cystic fibrosis this is end stage disease point in their lungs) - This Mutant MucA (selected in cystic fibrosis lung)--> has capsule genes that are active - Wild type MucA--> capsule genes inactive

Systolic BP increase could be due to is affects on

alpha1, beta2, beta1

A partial agonist has agonist acvtivity but also

antagonizes effect of full agonist (ex. endogenous ligand)

Most of the clinically important anticholinergic drugs are

antimuscarinic (M1, M2, M3) ** Understanding of predominant tone is important for ganglionic blockers (Nn)-- Antinicotinic (Nn and Nm)

Rationalization

concealing the true motivations for his or her own thoughts, actions or feelings through the elaboration of reassuring or self-serving but incorrect explanations

Conidia are spores produced by

filamentous fungi on surfaces (nasal passages; leftovers; in lab cultures) - Airborne: most 3 micron range - Used in identification of fungal cultures - Found in huge numbers in compost piles, moldy leftovers - Dangerous to transplant patients and other immunocompromised patients

Intrinsic activity, Partial agonist, and competitive antagonist

how "well" does the drug activate the target (relative to a full agonist) Intrinsic activity: - agonist (partial between 0-1, 0-100%), 1 or 100% for full agonist - antagonist, 0, 0% - inverse agonist: less than 0, less than 0% Partial agonist: cannot produce the same maximal effect as a full agonist; has partial efficacy, intrinsic activity is greater than 0 but less than 1.0 (less than 100%) Competitive antagonist: binds to the target (has affinity) but cannot activate the target; efficacy is 0, intrinsic activty is 0

Therapeutic index of a drug

ratio between a median harmful dose and a median effective does of a drug ex: LD50/ED50; TD50/ED50 NOTE: TD1/ED99 is sometimes called the margin of safety

Drugs and other molecules can go through epithelial cells by either

simple diffusion or carrier-mediated mechanism Carrier-mediated processes include: active transport and facilitate diffusion Various carrier-mediated systems (transporters) are present at the intestinal brush border and basolateral membrane: - Influx transporters (increase drug absorption)- move drug molecules into the blood and increase plasma drug concentration - Efflux transporters (decrease drug absorption)- move drug molecules back into the gut lumen and reduce systemic drug absorption

Metabolism is the

sum of anabolic and catabolic reactions in the cell Anabolic reactions: biosynthesis of macromolecules for cellular components Catabolic reactions: breaking down larger molecules to form building blocks for growth

Transformation

the uptake of naked DNA Process: 1. Donor cell 2. Cell lysis; release of DNA fragments 3. DNA enters recipient cell and integrates into DNA Exs of impact of transformation on bacterial pathogens: - Streptococcus pneumoniae - Haemophilus influenzae *These are significant cause of menigitis and otitis media (leading cause of parents missing work is bc child has an ear ache) - capsule plays an important role in pathogenesis - there are two examples of naturally COMPETENT pathogens - capsule genes of non capsulated strains are acquired by transformation (they have picked up the ability to make capsules, without the capsule they are NO longer virulent)

Undoing

words or behavior designed to negate or make amends symbolically for unacceptable thoughts, feelings or actions

Examples of CYP P450 induces and inhibitors

"barbie's race car goes phast" for inducers: - barbiturates, rifampin, carbamazepine, griseofulvin, phenytoin Ex: Carbamazepine is an inducer of several potential pathways of drug elimination, including CYPs 1A2, 2C9, and 3A4, as well as the active transporter P-glycoprotein - carbamazepine is primarily metabolized by CYP3A4 & it also induces its OWN metabolism (it is an auto-inducer) *** Any drug that undergoes metabolism via CYP1A2, CYP2C9, or CYP3A4 or is a substrate for the P-glycoprotein transporter, is likely to be affected by cabamazepine administration "clearly, cool ken's vehicle is equally quick" for inhibitors: - clarithromycin, cimetidine, ketoconazole, valproic acid, isoniazid, erythromycin, quinidine

For direct detection: microscopy of stained biopsy sections one should order

"fungal stains" - Gomori Silver stain: fungi black - Periodic Acid Schiff (PAS) reaction fungi pink (hot) - Calcofluor white- No antibody; just affinity for fungal cell wall - Mucicarmine- stains capsule of Cryptococcus neoformans pink - Immunofluorescent stains

Enterobius Vermicularis

#1 in US- seen in children- must treat the whole family! Very common in US - children most affected - PINWORM (common name) Mode: hand to mouth Site: intestine Diagnosis: eggs on anal region (PERIANAL ITCHING) ** Diagnosis with Scotch^TM tape technique - put in anus take out then put on a slide ** be able to recognize its eggs!!

What vaccine should be given for Neisseria meningitidis- 2 types (meningococcal disease)

(1) Capsule polysaccharide- protein conjugate- Serotypes A, C, W, & Y (2) Recombinant proteins (Neisserial adhesin A (NadA), Neisserial Heparin Binding Antigen (NHBA) and factor H binding protein (fHbp))- Serotype B Should be received by: (1) Adolescents and high-risk pts (ex. asplenia), children travelling to epidemic areas (2) Adolescents and high-risk pts (ex. asplenia and other high-risk pts)

What vaccine should be given for Streptococcus pneumoniae- 2 types (PCV13, PPSV23) (pneumococcal disease; meningitis)

(1) Capsule polysaccharide-protein conjugate (13-valent PCV13) (2) Capsule polysaccharides (23-valent PPSV23), adjuv. Should be received by: (1) (2) Children, adolescents, and elderly, high-risk pts (ex. asplenia)

AMA Code of Ethics' opinion about Professionalism in the Use of Social Media

- A residency director could ask about specific posts to make a judgment about the physician - Medical students should weigh a number of considerations when maintaining a presence online - Med students have a responsibility to bring that content to the attention of the individual - Participating in social networking create new challenges to the pt-phys relationship

List the dsDNA (linear, circular) viruses

- Adenoviridae (naked) - Herpesviridae (enveloped) - Papillomaviridae (naked) * these are DNA

Tissue Nematodes Filaria

- Adults in tissue - eggs NOT produced - Microfilariae produced 2 groups are imporatant in causing elephantiasis**: - Wuchereria bancrofti - Brugia malayi - Brugia timori **** vecotr= mosquito Loa Loa (vector= deer fly) Onchocerca volvulus (vector= black fly) Dracunculus medinensis (vector= water flea)

Clinical Uses for Epinephrine

- Anaphylaxis: emergency treatment of type I allergic reactions caused by drugs and other allergens. First choice drug anaphylactic shock - Restore cardiac rhythm in pt with cardiac effect (beta1) - Topically to prevent bleeding- mouth or peptic ulcers (alpha1) - Prolong the action of local anesthetics: local vasoconstriction slows entry of the local anesthetic into the blood- this also results in increased safety; lowers the risk of systemic local anesthetic toxicity - Mydriasis during intraocular surgery (alpha1) Adverese effects (mostly predictable based on site of action): - Ventricular arrhythmia - Cerebral hemorrhage from sharp rise in BP - Headache - Tremor - Renal insufficiency - Hypokalemia - Increased glucose - Anxiety - Pulmonary edema Contraindications: - Hypertension - Hyperthyroidism - Angina - Cardiac disease- arrhythmias and coronary artery disease - Pheochromocytoma - Diabetes

Signal transmission at a cholinergic synapse

- Choline req. for synthesis of ACh is transported into nerve terminal by the Na+ dependent transporter CHT - Enzyme ChAT catalyzes the synthesis of ACh from choline and acetyl CoA - ACh is transported into vesicles for storage by vesicular ACh transporter (VAChT) - ACh vesicles fuse with the plasma membrane and ACh is released from the vesicles when a presynaptic action potential triggers the release of Ca2+ from voltage gated Ca2+ channel - ACh diffuses into the synaptic cleft and binds to postsynaptic and presynaptic receptors- ACh receptors are divided into 2 types: Nicotinic (ligand gated ion channel) and muscarinic (GPCR) * Membrane bound acetylcholinesterase terminates the action of ACh by metabolism to choline and acetate

Measuring Disease Frequency has Several Components

- Classifying and categorizing disease - Deciding what constitutes a case of a disease in a study - finding a souce for ascertaining the cases - defining the population at risk of diasease - defining the period of time of risk of disease - obtaining permission to study people - making measurements of disease frequency - relating cases to population and time at risk **Studies are conducted in an attempt to discover associations between an exposure or risk factor and health outcome

In many viral infections, host immune responses are a major compoennt of the disease process

- Cytokines responsible for prodromal symptoms (flu-like) - Antiviral state --> Tissue destruction - Cell-mediated immunity (NK cells, IILs & IELs, CTLs) --> Tissue destruction - Immune complexes- Type III hypersensitivity (ex. glomerulonephritis)

Antitumor Effector Mechanisms include

- Cytotoxic T-lymphocyts (CD8+ CTLS) effective in EBV- and HPB-induced tumors - NK cells - Macrophages

Nonselective alpha/beta agonists

- Epinephrine - Norepinephrine - Dopamine ** these are naturally occuring in our body

What are the mechanisms of limitless replicative potential?

- Evasion of senscence via activation of telomerases and inhibition of cell cycle inhibitors - Evasion of mitotic crisis via telomerase reactivation during/after mitotic division - Self-renewal: maintenance of population of cancer stem cells

List the (+) ssRNA viruses

- Flaviviridae (enveloped) - Picornaviridae - Caliciviridae - Astroviridae - Hepeviridae ** The rest are naked and they are all RNA

What are some causes and examples of physiologic hypertrophy (increase in cell size)?

- Increased mechanical demand (skeletal muscles and LV myocardium in athletes) - Increased endocrine stimulation (smooth muscle cells in myometrium during pregnancy (along with hyperplasia), and ductal epithelium in lactating breast)

Summary of Alphaherpesvirinae

- Lytic cycle in epithelial cells - Skin lesions: cytopathic effects & inflammaiton - Latent infection in neurons - Cause orolabial and genital herpes, chickenpox (varicella), zoster (shingles) - Contact transmission (HHV-1/HHV-2) and aerosols (HHV-3) Immunity (only good for containment): - innate response: antiviral response, NK cells, IELs and activated macrophages - Th1 response: mostly CTLs - Humoral: IgG and IgA - Viral immmune subversion mechanisms Diagnosis: - Clinical presentation - NAT - Serology - Immunofluorescence Treatment: - Nucleoside analogs: Acyclovir

Cholinergic Receptor Signal Transduction

- M3/M1 activation is mediated by Gq--> increases PLC and IP3 and DAG--> Ca2+ influx is increased - Nn receptor activation opens a cation channel--> rapid influx of Na+ and Ca2+ - M2 receptor activation --> Gi --> opens K+ channels located in SA node, AV node, and atrial cells--> Results in negative chronotropic and dromotropic effects

What are some ways the fungi can infect humans?

- Many fungi produce large numbers of air-borne spores. (Fungi are major recyclers of organic material in the world). Fungal spores are found at low levels in our air much of the time. Other times, huge numbers may be present. Inhalation is route of infection - Some fungi are found in soil and plant material and infect humans through traumatic implantation - Some fungi are part of our normal cutaneous of mucosal flora (transmitted by passage through birth canal, direct contact, or fomites) - Normal fungal flora may overgrow under certain conditions and cause infections (ex. Antibiotic use, immunocompromised) - Normal fungal flora may also enter normally sterile sites and cause infection (Fungemia, Endocarditis)

Examples of why Immunization works

- Most physicians never see a case of Diphtheria now after vaccination began in 1930s - Since 1979, there has not been an autochthonous of polio in the U.S (Vaccination- Salk vaccine=IPV-- began in 1955) - Smallpox was eradicaed after vaccination by 1979 - Measles was declared eliminated from US in 2000- the disease has since made a comeback

How does cancer escape from Immune surveillance

- Selective outgrowth of antigen-negative variants - Loss or reduced expression of MHC molecules - Secretion of immunosuppressive factors by cancer cells, ex. TGF-beta etc.

What are the different patterns of viral disease?

- Self-limiting can lead to immunity or death - Peristent infection with shedding (i.e. Mono) - Perisistent infection with latency (i.e. HSV1,2,3) - Persisitent slow infection follow acut infection (i.e. HIV AIDS) - Prions (in CNS)

Interference with cyclins, CDKs, CKIs, checkpoint inhibitors and tumor suppressors can

- increase cell cycling - arrest T and B cell cycling to inhibit T- and B cell-mediated immune responses

Spirochetes DO NOT gram stain- describe them

- long, flexible spirals - endoflagella - gram-negative cell envelope - diagnose by FTA-ABS, serology Include: - Treponema - Borrelia - Leptospira

Triad of classic sxs for infectious mono is

- lymphadenopathy (swollen glands) - splenomegality (large spleen) - exudative pharyngities accompanied by high fever, malaise, and often hepatosplenomegaly (large liver and spleen)

Bacteria usually have more than one way to adhere:

- molecular adhesins on microbes attach to the surface receptors on host cells - adhesin-receptor interaction determines tissue specificity (tropism) - most pathogens have multiple attachment mechanisms - often very visible to the immune system

Sympathetic NS directly influences 4 variables:

- peripheral vascular resistance - heart rate - force - venous tone Parasymp NS directily influences heart rate ** AngII stimulates aldosterone secretion and increases peripheral vascular resistance

List the intestinal Sporozoa in order of prevelance in US

1. Cryptosporidium parvum/hominis "Cryptosporidosis" 2. Cyclospora cayetanensis "Cyclosporiasis" 3. Isopora belli "Isosporiasis" Mode: Ingestion of oocyst (water, food, SWIMMING POOL***) Site: - infection of intestinal epithelium - self limiting in immunocompetent persons - sporogeny/schizogony (sexual/asexxual stages) Diagnosis: *** ACID-FAST OOCYST in feces

Oncogenic viruses contribute to cell immortalization (cell transformation) primarily by

1. activating and/or providing oncogenes 2. interfering with the cell cycle 3. preventing apoptosis 4. inducing and/or provising growth-stimulating cytokines 5. induction of chronic inflammation ***Often, oncogenesis results from combination of these***

Hookworms

2 types: Necator americanus Ancylostoma duodenale Mode: penetration of bare foot (GROUND ITCH) Site: attach to intestine Diagnosis: eggs in feces ** Can also cause anemia and blood loss

Human Herpesviruses 6 and 7

2 variants of HHV-6: HHV-6A and HHV-6B, and HHV-7 are members of the genus Roseolovirus of the subfamily Betaherpesvirinae - At least 45% of pop is seropositive for HHV-6 by age 2 yr and almost 100% by adulthood **HHV-6 is serologically associated with a common disease of children, exanthem subitum, commonly known as roseola (HHV-7 also causes exanthem subitum) HHV-6: - occurs very early in life- replicated in salivary gland, is shed, and is transmitted in saliva - primarily infects lymphocytes especially CD4 T cells - establishes a latent infection in T cells and monocytes but may replicate on activation of the cells ** Cells in which the virus is replicating appear large and refractile and have occasional intranuclear and intracytoplasmic inclusion bodies--- similar to replication of CMV, the replication of HHV-6 is controlled by cell-mediated immunity - similar to CMV< virus is likely to become activated in pts with AIDS or other lymphoproliferative and immunosuppressive disorders and cause opportunisitc disease

Human viral pathogens are contained in around

26 families (17 of which are RNA viruses) - Viruses of the SAME family can cause different diseases (ex. Picornaviridae can cause poliomyelitis, common colds, hepatitis, pharyngitis) - Viruses from DIFFERENT families can cause the same disease (ex. Diarrhea can be caused be Reoviridae, Caliciviridae, Adenoviridae, Astroviridae)

Varicella (chickenpox) is one of the

5 classic childhood exanthems (along with rubella, roseola, 5th disease, and measles) Includes: - fever & maculopapular rash that appear after an incubation period of apprx 14 days. - within hrs, each maculopapular lesion forms a thin-walled vesicle on an erythematous base ("dewdrop on a rose petal") that measures apprx 2-4 mm in diameter (this is the hallmark of varicella) - Within 12 hrs, veiscle becomes pustular and begins to crust, after which scabbed lesions appear- succesive crops of lesions appear for 3-5 days and at any given time all stages of skin lesions can be observed Rash spreads across body but more prevalent in trunk and head - presence on scalp distinguishes it from many other rashes Lesions itch and cause scratching --> may lead to bacterial superinfection & scarring - lesions on mucous membrane typically occur in mouth, conjunctivae, and vagina Primary infection is more severe in adults than in childrean (interstitial pneumonia may occur in 20-30% of adult pts and may be fatal) -- pneumonia results from inflamm reactions at this primary site of infection Herpes zoster= recurrence of a latent varicella infection acquired earlier in the pts life - severe pain in the area innervated by the nerve usually precedes the appearance of the chickenpox-like lesions - the rash is limited to a dermatome and resembles varicella Postherpetic neuralgia (chronic pain syndrome)--> persists for months to yrs, occurs in as many as 30% of pts whom herpes zoster develops

Describe the Prokaryotic Ribosome

70S (5S rRNA + 23S rRNA) + 34 polypeptides --> 50S subunit 16S rRNA + 21 polypeptides --> 30S subunit So 50S + 30S --> Prokaryotic 70S Ribosome *** The Prokaryotic ribosome is a drug target - Tetracyclines, for ex, bind to a site within the 30S subunit preventing tRNA attachment

Pharmacologic Properties of Choline esters

ACh: sensitive to cholinesterases*, works on M1, M2, M3 muscaring receptors and nicotinic receptors Carbachol: selective for M1, M2, M3 muscarinig and nicotinix receptors Bethanechol: selective for M1, M2, M3 receptors- NOT nicotinic*

Describe regulation of receptor number

Activation--> Desensitization--> Internalization --> Resensitization or Down-regulation There can be Chronic Activation or Inhibition of receptors Chronic activation of receptors: - When receptors are chronically activated by an agonist drug, the pharmacological response can decrease with time, a process called desensitization or down-regulation **** can lead to drug tolerance Chronic inhibition of receptors: - When receptors are chronically inhibited by an antagonist drug, the pharamacolofical response can increase with time, a process called sensitization or supersensitivity - This increased response can be evident once the antagonist drug is suddenly removed. Mechanisms include the up-regulation of receptors that are increased in number due to either decreased destruction or increased synthesis

Define: Agonist, Antagonist, "Mimetic", "Lytic"

Agonist: A drug or natural ligand that activates a receptor as a direct result of binding to it (activation of a receptor means that signaling occurs, this signal can be negaive or positive) Antagonist: Drugs that bind to a receptor but do not activate the generation of a signal (negative or positive, when an antagonist is bound to a receptor nothing happens). An antagonist opposes the action of an agonist. "Mimetic": Mimicking the action of a NT - Sympathomimetic: drug the mimics the symp NT (NE or Epi) - Cholinomimetic: drug that mimics the actions of ACh "Lytic": Oppose the actions of NT - Sympatholytic: oppose/antagonize the actions of NE or Epi (antiadrenergic) - Cholinolytic: oppose/antagonize the actions of ACh (anticholinergic)

Adrenergic receptor types and locations

Alpha adrenaoreceptors - Alpha1: in smooth muscle*, dilator pupillae*, prostate*, gastrointestinal sphincters, and CNS - Alpha2: in presynaptic autoreceptors and CNS*, ciliary epithelium*, platelets, salivary glands, pancreatic islates and adipocytes Beta adrenoreceptors - Beta1: heart* and kidney - Beta2: Bronchioles*, blood vessels of skeletal muscle*, liver, uterus and gastrointestinal tract - Beta3: Adipocytes and some smooth muscles (detrusor*) Dopamine - D1: vascular smooth muscle (renal and mesenteric vascular beds) and CNS - D2: CNS *= common receptor locations targeted by drugs

Deal with emotional conflict or internal or external stressors by dedication to meeting the needs of others. Unlike the self-sacrifice sometimes characteristic of rx. formation, the individual receives gratification either vicariously or from the response of others

Altruism

Naegleria fowleri

An Amoeboflagellate (Primary CNS Pathogen) **MORE aggressive than the other pathogen Acanthamoeba culbertsoni Mode: infection of nasal passages (swimming/diving) Site: CNS (amoebic meningoencephalitis) Diagnosis: trophozoite in CSF

Amyloid

An abnormal protein, product of defective folding (beta-pleated sheets instead of alpha-helices) Identification: - Congo red stain: brightly pink/red on weakly pink background - Fluorescent microscopy of Congo-red stained slides: apple-green birefringence Ex: Renal Amyloidosis

Metyrosine

An indirect acting antiadrenergic drug MOA: Inhibition of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis Clinical uses: Pheochromocytoma- before surgery, or long term management for malignant pheochromocytoma Adverse effects: - Orthostatic hypotension (predictable bc no vasoconstriction from alpha1) - Sedation (from CNS problems)

A histology slide that shows scattered, individual epidermal cells with shrunken, markedly eosinophilic cytoplasm and pyknotic, fragmented nuclei is most likely due to

Apoptosis ** remember pyknosis is "shrinkage"

Mollicutes

Are different from gram + or - Have a soft, pleomorphic structure- NO CELL WALL - Extracellular bacteria - Membrane contains sterols, acquired from host (give some rigidity) - Very small (0.2-0.3 micrometers): can pass through most filters, too small to see by light microscopy ** these are the minimalist of bacteria- they are probably the smallest bacteria that can cause a human infection - Gram stain is not useful - Genera of important are: Mycoplasma, Ureaplasma**

Give an example of the relevance of horizontal gene transfer to pathogenesis

Avirulent E coli and Virulent E coli 1. Transfer Virulence genes either via: - conjugation - transduction - transformation 2. Change to Virulence 3. Intestinal disease due to virulence genes - adherence - enterotoxins - invasiveness - cytotoxicity

Microbial Identification is

Based on properties of an organism - morphology, metabolism, products and is a Process designed to produce a combination of results unique to a particular pathogen: - could be as "simple" as microscopy of an organism with a unique appearance, a PCR result, or a protein fingerprint - could require multistep process, using microscopy, growth characteristics, and biochemical tests

Dobutamine has receptor affinity for

Beta1

Naturalist vs. Normative model of health

Biomedical (or naturalist) model: - human states of health or disease are based strictly on biological facts of nature - social normal, subjective considerations or value judgments have no role - implications for the bearer of health or disease are NOT considered - value free Normative model: - health and disease are inseparable from social and culturally determined value judgments - what "counts" as disease can change radically over time and across cultures

Local growth of Malignant Tumors

Carcinoma: classical invasive growth with crab claw-like sprouts - starts from penetration of basement membrane (BM) ** carcinoma in situ= no BM penetration= not a cancer - Carcinoma with microinvasions is a cancer but with a good prognosis Sarcoma and lymphoma: infiltration of surrounding tissues, often not seen by naked eye Exophytic growth: a malignant neoplasm projects out from the epithelial surface (i.e. mass protruding into the lumen of the colon) - the same tumo also grows downward with penetration of the underlying BM

Gram positive cocci can either be catalase + or -

Catalase +? Staphylococci (facultative anaerobes) Catalase -? Streptococci/Enterococci (anaerobes) Catalase: breaks down hydrogen peroxide to water and oxygen 2H2O2 --> 2H2O + O2 ** positive test gives bubbles

Trypanosoma cruzi

Cause of: - American trypanosomiasis - Chaga's disease (enlarged heart and intestine) Vector: reduviid bug (Triatoma) - "kissing bug" - "triatomine bug"

Adpative Immune Defenses to Viruses

Cell and antibody-mediated immunity: - tailored t specific invading virus - slow compared to innate defenses - virus neutralization - immune complexes (destroyed by macrophages) - responsible for long term immunity (memory) Review: - Antigen presentation and T lymphocyte activation - TH1 response - T-dependent B lymphocyte activation and antibodies - Cytotoxic T lymphocytes - Complement - Antibody-dependent Cell cytotoxicity

Beta-lactams, Vancomycin, Fosfomycin all act as

Cell wall synthesis inhibits BUT by diff mechanism Beta-lactams--> inhibit transpeptidases Vancomycin--> inhibits transglycosylase Fosfomycin--> inhibits enolpyruvate transferase

Sublimation

Channeling potentially maladaptive feelings or impulses into socially acceptable behavior (ex. contact sports to channel angry impulses)

Direct Acting Cholinergic Drugs- Muscarinic Agonists include

Choline Esters and Natural Alkaloids Choline Esters: - Acetylcholine - Carbachol - Bethanechol Natural Alkaloids: - Pilocarpine - Muscarine

Human chorionic gonadotropin (hCG) is a marker for

Choriocarcinoma

Vibrio Cholerae

Clinical features: Severe watery diarrhea Microbiology features: - G-curved rod - oxidase + - Motile - O1, O139 serotypes Epidemiological features: - children/adults in developing countries Virulence/pathogenesis features: - Cholera toxin - TCP - Several other toxins Treatment: - Oral rehydration - Doxycycline - Limited vaccine effectiveness

A male committed suicide by ingesting an unidentified toxin, after which he went into profoudn shock and died - what would kidney histology most likely find

Coagulative necrosis - Grossly: finding would be a small renal lesion which was reddish-tan in color, sharply delineated, and triangular in shape - Histology: would find a necrotic glomerulus and tubules

Carcinoembryonic antigen (CEA) is a marker for

Colon and pancreatic carcinoma

Curing vs. Healing

Curing= eliminating disease - passive - primarily only the body Healing= restorng "wholeness" - active - body, psyche, even "spirit"

Describe the morphology of Irreversible cell injury

Cytomembrane rupture Mitochondria: - severe swelling - rupture of cristae - ** rupture of membranes - ** large amorphous densities (calcium and/or phospholipids)

What are some activators of p53?

DNA damage and other severe stressors (ex. anoxia, irradiation, etc) Function: 1. Cell cycle arrest at G1/S through activation of p21--> inhibition of cyclin E/CDK2--> arrest at G1/S 2. Activation of DNA repair 3. Apoptosis, if DNA repair was unsuccessful, through activation of BAX (BCL-2 family) 4. Activation of cell senscence Cells with mutations or loss of p53--> DNA damage-->--> Malignant tumor p53 inactivation: Loss-of-function mutation of TP53 gene on chr. 17p Acquired p53 mutation: - 50% of all cancers including lung, breast, and colon carcinoma Inherited TP53 mutation (Li-Fraumeni Syndrome): - Rare type of p53 mutation - by age of 50 - Sarcoma, breast carcinoma, leukemia, **brain tumors, and ** adrenal cortex carcinoma ** Pt with brain tumor or adrenal cortex carcinoma most likely due to Li-Fraumeni Syndrome

Humor

Deal with emotional conflict or external stressors by emphasizing the amusing or ironic aspects of the conflict or stressors

Describe prokaryotic Translation

Decoding mRNA into chain of AA, forming a polypeptide - A codon is a seq of 3 DNA or RNA nucleotides that corresponds with a specific AA or stop signal during protein synthesis - Language or proteins includes 20AA AUG= Start (Met), (fMET for prokaryotes) - UAA, UAG, UGA= Step - UGA= selenocysteine (SeCys) Transfer RNAs (tRNAs) carry a particular anticodin AA combination

Deal with emotional conflict or internal or external stressors by attributing exaggerated neg. qualities to self or others

Devaluation

Which NSAID is - available for opthalmic and topical delivery

Diclofenac Naproxen

Toxin production by Steptococcus Pyogees allows

Dissemination - Streptococcus Pyogenes turned off ability to regulate the toxin --> toxin then chews away cells and the organism can escape and move deeper into tissues

What are the 3 tRNA attachment sites within the ribosome?

E,P,A - During elongation- the next tRNA binds in the A site of the ribosome - Peptide chain at P site is transferred to the newest AA in the A site - Ribsome moves down one codon towards 3' end (translocation) and the uncharged tRNA (here, the one that carried fMet) is released - Termination: this proveeds until the stop codon is reached, for which there is no tRNA (UAG, UGA, UAA) - Release factors bind to stop codons, cleave the polypeptide from the last tRNA, and the ribosome dissociates

What is the normal function of E-Cadherin?

E-cadherin forms intercellular bridges attached to intracellular Beta-catetin molecules--> keeping close cell-to-cell contacts--> "contact inhibition" of cell proliferation Loss-of-function mutation in E-cadherin gene (CDH1)--> loss of contact inhibition --> activation of cell proliferation, invasive growth, and progress through metastatic cascade Inhertied vs. Sporadic Mutation of E-Cadherin Germline loss-of-function mutation in CDH1 gene--> familial gastric carcinoma Sporadic mutation in CDH1 gene--> reduced cell surface expression of E-cadherin - Lobular breast carcinoma* - Diffuse type of sporadic gastric carcinoma - Other carcinomas: esophagus, colon, ovary and prostate

Markers of Epstein-Barr Virus (EBV)

EBV nuclear antigens (EBNAs)- nuclear--> these are nonstructural antigen and first antigens to appear, seen in all infected and transformed cells ---- Anti-EBNA developes after resolution of infection Early antigen (EA-R)- only cytoplasmic---> appears before EA-D; appearance is first sign that infected cell has entered lytic cycle EA-D- diffuse in cytoplasm and nucleus--- Anti-EA-D seen in infectious mononucleosis Viral capsid antigen (VCA)- cytoplasmic --> late proteins; dfound in virus-producing cells----Anti-VCA IgM is transient; anti-VCA IgG is persistent Membrane antigen (MA)- cell surface--> are enveloped glycoproteins-- same as VCA Heterophile antibody - recognition of Paul-Bunnell antigen on sheep, horse, or bovine erythrocytes --> EBV-induced B-cell proliferation promotes production of heterophile antibody ---> early sx occur in more than 50% of pts

Differntiate between immediate early, early, late proteins

Early: proteins for genome replication (ex. polymerases) Late: structural proteins (ex. capsid proteins) Immediate early: only some viruses and transcription factors to direct host machinery to prefer viral promoters

Microskills in Interviewing

Empathy: - empathy= how "pt" feels, sympathy= how "physician" feels; sympathy drains the physician- empathy is data that can help diagnose and treat thus empowering the physician - this is the most important relationship-building skill the physician can possess - listen carefully, enter the world of pt., communicate that you "imagine" the pts world as pt sees and experiences it - yet DO NOT become the pt (you relate but also remain separae) - mirror neurons- basis of our ability to sense world of client - grounded in POSITIVE REGARD- "accept the person and reject the behavior" Respect and Warmth: - Attitudinal dimensions usually shown through nonverbal means- smiling, touching, and respectful tone of voice- even when diff in values are apparent between interviewer and pt - Demonstrated by open posture (SOLAR), similing, and vocal qualities (Be congruent with your body language) Concreteness: -Seek specific feelings, thoughts, descriptions, and ex. of action: " Give me and example of ...? (interviewer leads need to be very specific)- directive, feedback, interpretation Immediacy (hear and now): - Be in the moment with the pt - Most powerful response is often in the present tense - Change of tense may speef up or slow down the interview- shifting to new tense from pts constant tense may be useful Nonjudgmental Attitude: - Suspend your own opinions and attitudes- assume a value of neutrality - Interviewers may be challeneged by dishonest, violent, sexist and/or racist pts Authenticity & Congruence: - Are you personally grounded in the present? - Phys. flexibility when responding to the pt demonstrates authenticity - authenticity & congruence are reverse of discrepancies and mixed messages Confrontation: - Skilled & nonjudgmental confrontation encourages pts to talk in more detail and to resolve their problems - This is not a direct, harsh challenge: "it is not going against but with the pt" - enables resolution of difficulties and establishes healthy lifestyle

T or F: Medical errors can be changed even after a note has been signed

FALSE! - CANNOT be changed once a note is signed - instead, errors must be documents/corrected via addendum in the medical record ** Avoid dangerous abbreviations- DONT use abbreviations for drug names or decimal points and zeros

A substance elaborated by macrophages is found at wound site to stimulate this capillary proliferation- which substance is most likely to have this function?

Fibroblast growth factor (FGF)

Classification schemes for bacteria

Formal Rank: - Family (Ex. Enterobacteriaceae) - Genus (Ex. Escherichia) - Species (Ex. Coli) - Subspecies (O157H7- 2 androgens on the outside of bacterial cell, gives more detail) NOTE: Only the rank of family, genus, species, and subspecies are commonly used and usually just genus and species Ex. Anotherdeadmicrobiologistella shamelesslylookedoverii (first word upper case, second is lower case)

Give examples of drugs that are functional antagonist to eachother and physiological antagonists

Functional antagonists: Ex1: Cocaine increases dopamine levels and haloperidol blocks D2 receptors - actions of cocaine are opposed by haloperidol, but the drugs act at different sites Ex2: Amphetamine is a stimulant and ethanol is a CNS depressant - actions of amphetamine are opposed by ethanol, but the drugs act at different sites Physiological + Functional antagonist: Ex1: Muscarinic agonists (ex. Ach) promote contraction of smooth muscle, whereas beta-2 agonists (ex. albuterol, epinephrine) promote relaxation of smooth muscle - opposing actions through activation of DIFFERENT receptors - physiological antagonist bc endogenous molecules that can oppose eachother

Describe Dimorphic Fungi

Fungi exist as mold/filamentous/hyphal form or as yeast - generally, in the environment (25-30 degrees celsius) a dimorphic fungus will grow as a mold - 37 degrees celsisus--> yeast - In the COLD--> MOLD Major US dimorphic pathogens are the genera: - Histoplasma - Blastomyces - Coccidioides - Sporothrix

Size of microrganisms

Fungus> Bacteria> Virus - Microscopic protozoa and fungi (4-10micrometers)- can almost be seen unaided with the human eye ** Fungi are 4-10x larger than bacterium - Bacteria (0.1-10micrometers)- seen with light microscope [ Ex. E. coli ~1micrometer diameter and 2 micrometer length ] - Viruses (0.03-0.3micrometers)- seen with electron microscope some with light microscope ** Know these measurements

Randomized Clinical/Control Tiral (RCT)

GOLD STANDARD for evaluating treatment effects Trial: experimental test of a treatment - Clinical trial: eligible particpants must have a diagnosis. Compares therapeutic benefits of 2 or more treatments or of treatment compared with placebo - Randomized clinical/control triall: eligible particpants are sorted fairly equally into treatment conditions - double-blind randomized clinical/control trial: neither subjects nor the clinicians who evaluate them know their treatment status Important notes: - Experimental study: researcher manipulates who is in what group - Study quality improves when the study is randomized, controlled, and double blinded Typically has 4 Phases: I (small #- 50-100 healthy volunteers): Is it safe? II (Moderate # pts with disease of interest): Does it work? III (large # pts randomly assinged to tx/placebo): Is it as good or better? (any improvement?_ IV (post marketing surveillance of pts after tx approved): Can it stay?- detecs rare or long-term adveres effects -- can result in treatment being withdrawn from the market

Glial fibrillary acidic protein (GFAP) is a marker for

Gliomas

What is the most common Phase 2 reaction in the biotransformation (metabolism) of drugs?

Glucuronidation - compounds are conjugates with glucuronic acid - occurs mainly in the liver and catalyzed by a microsomal enzyme: UDP-glucuronosyltransferase

Activation of alpha1 receptors leads to the activation of the

Gq protein --> increased PLC --> IP3 & DAG - IP3 stimulates release of stored calcium and cytoplasmic Ca2+ concentration increases

Activation of ALL beta receptors leads to activation of the

Gs protein --> increased adenylyl cyclase --> increased cAMP (PKA activated by cAMP--> PKA can then modify the activity of other proteins in the cells such as ion channels)

A pt with congenital anemia who has req multiple transfusion of RBCs for many yrs- with no other sig findings on phys examination- microscopic finding most likely in the liver is

Hemosiderin in hepatocytes

Trematodes

Hermaphroditis flukes: - definitive host--> mammal Mode of infection: - fish - crustacean (ex. crab) - vegetable Schistosomes (exception; blood fluke) - definitive host--> mammal - Mode of infection: skin penetration--> swimming Lung fluke- Paragonimus westermanii (crab) Liver flukes: Clonorchis sinesis (fish) Fasciola hepatica (plant/vegetable) Intestinal flukes: Heterophyes heterophes (fish) Fasciolopsis buski (plant/vegetable)

A pt with sneezing with watery eyes, runny nose for past 2 weeks, red, swollem nasal mucosal surfaces - when around ragweed pollen- her symptoms are most likely cause by what chemical mediator?

Histamine

A 75 y/o womens endometrium shows atrophy with thin endometrium with only a few atrophic and cystic glands- what could be the cause of this endometrial atrophy?

Hormonal deprivation

Hyaline Arteriolosclerosis

Hyaline in the wall of small arteries (arterioles) Content: collagen, plasma proteins, necrotic debris of smooth muscle cells Etiology: - Hypertension - Diabetes mellitus ** A type of EXTRACELLULAR hyaline accumulation

Differentiate the Adaptive Responses of Hypertrophy vs. Hyperplasia

Hypertrophy: increase in cell size (seen in stable and permanent cells) Hyperplasia: an increase in cell number (seen in labile and stable cells) ** Hyperplasia and hypertrophy may occur simultaneously (stable cells) - BOTH hyperplasia and hypertrophy result in an increase of organ weight and volume

Which NSAID is - very potent and should only be considered when one of the other less toxic agents are ineffective - used to accelerate closure of patent ductus arteriosus - also available for opthalmic, epidural

Indomethacin

Describe theta replication of bacteria

Initiator proteins for replication: DnaA, DnaB (DNA helicase), and DnaC - DnaA- directs replication initiation (primosome formation) - Strands are separated by DNA helicase, at the replication fork ("unzips" DNA molecule) - Strands are bound by SSB protein stabilizing the single strands - Primase (DNA-dependent RNA polymerase) generated short RNA oligonucleotides= primers

A critical element of bacterial growth in vivo is

Iron acquisition - Many bacteria secrete small molecules that bind iron (siderophores) - Siderophores (with bound iron) are then internalized via receptors by the bacterial cell ** Siderophores try to sequester free iron from your host--> human host and bacteria always fighting for iron

ELISA (Enzyme Linked Immunosorbent Assay)

Is a very sensitive test for detection of small amounts of antigen or antibody in form of antigen-antibody complexes - An enzyme, such as alkaline phosphatase or horseradiah peroxidase is coupled to antibody to generate a colored product when exposed to a suitable substrate - The amt of antibody bound is proportional to amt of color generated - The ELISA test as applied to HIV screening is designed to detect antibody in human serum to HIV antigen

What is a drug interaction- what are the different types that exsist?

It is a measurable modification of the action of one drug by administration of another substance (drug, food, or environmental agent). Drug interactions can increase or decrease drug effects 4 Types: - Addition: response of drugs combined is equal to combined responses of both drugs (1+1=2) - Synergism: response of combined drugs is greater than the combined responses of individual drugs (1+1>2) - Potentiation: drug with no effect by itself enhances effects of another drug (0+1>1) - Antagonism: response by combined drugs is lower than response of individual drug (0+1<1 , 1+1<1)

Entamoeba Histolytica (Amoebiasis)

Main pathogenic protozoa in the body - World-wide distribution - Poor sanitary conditions Modes of transmission: - contaminated water (food) - hand-mouth ***fecal-oral transmission - sexual Site of infection: - intestine - **may become extraintestinal (liver abscess, etc.) - this is if the infection becomes invasic through the bloodstream, infecting sites such as the liver, brain, and lungs **Be able to recognize its trophozoite and cyst Diagnosis: - cysts in feces

How can alphaherpesvirinae be treated?

Mainly with Nucleoside Analogs: - Acyclovir - Famciclovir - Valacyclovir **these stop growth of DNA molecule

Microbial Resistance to Tetracyclines

Most strainds of staphylococci are now resistant to and resistance may emerge during treatment of an individual pt Resistant strains of S. Pneumoniae are common Mechanisms: - Resistance is usually plasmid-encoded. Main mechainsms are: - increased activity of the multidrug efflux pump - modification of the ribosomal binding site which decreases drug binding - enzymatic inactivation of the drug

In a normal cell RAS-GTP complex is inactivated by GAP (GTPase-activating protein) - (RAS-GTP) + GAP--> (RAS-GDP) + Pi + GAP What happens if RAS is mutated?

Mutated RAS is trapped by GAP in its activated form (RAS-GTP) and CANNOT dissociate to an inactive form (RAS-GDP)--> the cell will continue to grow or proliferate - K-RAS mutation: seen in lung, colon, pancreatic carcinoma - H-RAS - N-RAS NOTE: Mutations in GAP mimic mutations in RAS Ex: Mutation in neurofibromin-1 (a GAP) in neurofibromatosis type 1 (NF-1) Sxs: - Cafe-au-lait spots - Lisch nodules - Numerous neurofibromas

Clinical Use for Cholinesterase Inhibitors

Myasthenia gravis (therapeutic effect in somatic NS- NMJ) Treatment- Neostigmine and pyridostigmine - Distinguish between cholinergic crissis and myasthenic crisis --- Edrophonium (used bc its short acting) Reversal of poisoning anticholinergic drugs (ex. atropine) - physostigmine (bc it enters the CNS) Urinary retention - Neostigmine Reversal of non-depolarizing neuromuscular blockage: - Neostigmine Alzheimer Disease: - Donepezil (selective inhibitor of acetylcholinesterase in the brain)

Growth rates for bacteria vary substantially- can you give some examples

Mycobacterium tuberculosis - 37*C, Doubling time is 6days (**6 days, need apprx 45 days to do an experiment off them) Nitrobacter argilis 37*C, Doubling time is 20days Streptococcus Pyogenes rep in 12 min and in human blood this goes down to 7 min (this is why necrotizing fascitis can kill patients within hours --> rapidly doubles)

Gangrenous Necrosis

Necrosis of organs, which contact with environment (skin, lungs, and gut) - necrotic changes can be coagulative or liquefactive Usually black in color due to accumulation of iron sulphide Clinical Variants: Dry gangrene: - ischemic/coagulative necrosis of the limbs (usually lower) --> may progress to wet gangrene Wet gangrene: - necrosis with secondary bacterial infection and digestion of already dead tissue (liquefaction) Gas gangrene: - subtype of wet gangrene, directly caused by bacteria WITHOUT preceding tissue necrosis

After a gram-stain you find that the bacteria is a gram-negative cocci- what bacteria can it be?

Neisseria sp. - Diplococci - often associated with PMNs in direct smear - aerobes but like 5% CO2 - non-motile - need chocolate (CAP) or Thayer-martin agar for N. gonorrhoeae - oxidase (+), catalase (+) - some species normal in throat - N. gonorrhoeae (UG, eye) oxidizes glucose - N. meningitidis (blood, CNS) oxidizes glucose and maltose

Direct Acting Cholinergic Drugs- Nicotinic Agonists include

Nicotine (Acetylcholine) (Carbachol)

Most potent carcinogens (indirect initiators) include

Nitrosoamines and Nitrosoamides These are synthesized in the stomach from: - Amines and amides (= products of AA metabolism) + - Nitrates and nitrites (widely used as preservatives and fertilizers) ** These are proven to induce cancers in humans: Esophageal and Gastric carcinoma

CSF- India Ink (nigrosin) wet mount

ONLY for suspected cryptococcal meningitis, common in AIDS patients - CSF sediment is mounted in India ink. The ink particles do not penetrate the yeast polysaccharide capsule so you look for "halos" around budding yeasts - A "rule in" test only (misses 50% of cases. If positive, it provides a rapid diagnosis but other tests and cultures MUST also be done)

Effects of BOTH Benign and Malignant Tumors on the Host (Benign dont kill but can kill bc of these)

Occupation of confined space (i.e. Subarachnoid space by a brain or meningeal tumor) Obsrtuction of lumen (i.e. Renal artery by leiomyoma) Hormone production (ectopic hormone production) (i.e. Pituitary adenoma, Pheochromocytoma, Adrenal cortical adenoma) Destruction of blood vessels and bleeding (i.e. Gastric/colon adenoma or carcinoma) Ulceration (i.e. Gastric/colon carcinoma) Secondary infections: major cause of death in caancer pts (i.e. GI carcinoma with peritonitis, Lung cancer with penumonia, and Leukemia with pneumonia)

What are some structural changes that occur in reversible injury?

On EM you can identify: Mitochondria: - swelling/rarefaction of matrix (due to increased water) - small phospholid densities and small calcium densities ER: - dilation - detachement of ribosomes - vacuoles (on LM) Cytomembrane and cytoskeleton: - blebbing - blunting of microvilli - loosening of intercellular attachment ***Myelin figures: - Whorls of phospholipids originating from damaged membranes Lipid droplets: - Increased in amount and size - Lipid droplets (on LM) Polysomes: - Disintegrate into (mono)ribosomes

Herd immunity

Once a certain proportion of a population has achieved immunity, the natural transmission of a pathogen in that population can be halted i.e. if a large percentage of the population is immune to a pathogen, the entire population is likely to be protected from that pathogen

Comparing means can be t-test OR

One-way analysis of variance (ANOVA) - Similar to t-Test. However, it uses 3 groups or more - Used in hypothesis testing to determine the statistical diff. between 3 group means Independent vairable: one nominal (3 or more groups) Dependent variable: interval or ratio ---- or Two-way analysis of variance (ANOVA) Uses 2 independent variables (ex. sex, treatment group) - used in hypothesis testing to determine the statistical sig. between multiple group means and their interaction Independent variable: 2 nominal variables Dependent variable: interval or ratio

A concentration-time graph for a drug given orally differs from one given IV because?

Orally: conc starts at low dose and increases over time till reaching a CP max IV: conc starts at high dose then falls over time

Progression of Tumor

Over a period of time, many malignant tumors become more aggressive with: - accelerated growth rate - increased invasiveness - higher ability to form distant metastases - increased resistance to hypoxia - increased resistance to antineoplastic chemo- and radiotherapy Natural HIstory of Malignant tumors (progression): Mutations in a genetically unstable cell--> Transformation [formation of tumor-initiating cell (stem-cell-like)] --> Monoclonal growth (accumulation) of progeny of a tumor-initiating cell--> Heterogeneity: stepwise appearance of subpopulations of cells with different level of aggressiveness--> Survival of subpopulations of cells with higher malignant potential --> local invasive growth --> Distant spread (metastases)

Drug Distribution

Passage of drug from the systemic circulation to body tissues (ex. from the circulation to the target receptor) - A drug may initially distribute to organs with high blood flow- later lipophilic drugs may go into less vascular or adipose tissue (redistribution)- plasma drug concentration will decrease - A quantitative measure of drug distribution is acheived by pharmacokineticparameter: volume of distribution (Vd)

Describe a typical growth curve for bacterial culture

Phases: Lag Phase: - Liquid culture period of no growth- bateria getting ready Exponential phase: - Cells doubling rapid Stationary phase: -Amount of nutrients dop off - Cells dividing= cells dying Death phase: ** Turbidity (Optical density) will stay the same bc once cells die their viscosity will not change they will give the same light scattering effect (light scatter with increase density= optical density)

Cholinesterase Reactivator

Pralidoxime

Selective alpha-antagonists

Prazosin Tamsulosin

Pt taking acetylsalicylic acid (aspirin) for arthritis- pain is temp reduced despite continuing destruction- relief of pain most likely due to redult of diminishing which chemical mediator?

Prostaglandin E2

Prostate specific antigen (PSA) is a marker specific for

Prostate carcinoma

Overview of bacterial protein synthesis

Proteins are built from AAs on ribosomes - protein syn. is basically the same in prokaryotes and eukaryotes but ribosomes in eukaryotes are diff. and the syn. proteins are more complex - ribosomes in prokaryotes are composed of 2 subunits (30S and 50S) - ribosomes move along strands of mRNA so that successive codons pass through an accpetor site - under nml circumstances the nascent peptide is attached to the ribosome at peptidyl (P) site The next AA is bound to tRNA in the cytoplasm and the animoacyl tRNA binds to the acceptor (A) site of the ribosomes (this step is inhibited by tetracyclines***) Peptidyltransferase (a component of 50S subunit) catalyzes the transfer of the peptide chain from the P site onto the AA at the A site (this transpeptidation rx. is inhibited by chloramphenicol**) The ribosome advances 3 nucleotides so causing the transder of peptidyl tRNA from the A site to the P site (this translocation rx is inhibited by aminoglycosides, macrolides, lincosamides, and streptogramins***)

Role of the Clinical Microbiology Laboratory in Diagnosing infections

Provide accurate information regarding: - presence of microorganisms in a specimen - characterization/ID of the infectious agent - antimicrobial susceptibility, if possible/relevant Ability to achieve these goals is limited by: - quality of the specimen - specimen transportation - availability, sensitivity, specificity of diagnostic techniques Stepwise Process in laboratory: Patient --> Specimen collected--> Specimen transported --> Specimen received and processed --> Test performed --> result reported to physician --> physicia interprets result--> physician relates result to patient care

List the Enveloped viruses

RNA Enveloped viruses: - Retroviridae - Paramyxoviridae - Flaviviridae - Deltaviridae DNA Enveloped viruses: - Herpesviridae - Hepadnaviridae NOTE: alcohol is more likely to effect enveloped vs. naked virus (like hand sanitizer) Ex: Physician cleans hands with hand sanitizer after seeing pt with URI- which virus is she most likely to transmit? Adenovirus (it is a DNA naked virus which is more resistant to hand sanitizer and alcohol)

List the Naked viruses

RNA Naked viruses: - Picornaviridae - Reoviridae - Caliciviridae - Astroviridae - Hepeviridae DNA Naked viruses: - Adenoviridae - Papillomaviridae

How is flow cytometry used to diagnosis cancers?

Rapidly and quantitative measurement - cell volume (pleomorphism) - protein expression and localization (CD molecules in leukemias and lymphoma) - DNA content (ploidy and aneuploidy) in malignant and premalignant cells Ex: Anueploidy would show (2.8N vs. the 2N) in High-grade dysplasia and high risk of cancer with Barretts esophagus

What type of vaccine is shingles

Recombinant, adjuv. - shoulld be given to >50yo

What is the function of DNA polymerase I in prokaryotic replication?

Removes the RNA primers in the laggind strand - 5'-3' and 3'-5' exonuclease activity - filling gaps between Okazaki fragments - DNA pol I also replaces them with DNA (5'-3' polymerase activity - Nicks sealed by DNA ligase - Also serves to remove errors from the code

Pt presents with painful sweeling of R knww- along with morning stiffness in hands lasting for at least 6 hrs PE: soft tissue swelling and tenderness in proximal MCP joint Labs: - test for rehumatoid factor and anti-nuclear antibodies- positive - increased ESR - synovial fluid exam- increased protein and white cell count Imaging: - Narrowing of joint spaces and fusion of joint Histology shows: - Papillary projections with lymphoid follicle- chronic nonspecific inflammation and plasma cells Dx?

Rheumatoid Arthritis

Tamsulosin

Route of administration: oral MOA: Competitve inhibition of alpha1 receptors, it may selectively block alpha1A receptors (alpha1A receptor may be more important for contraction of prostate smooth muscle than vascular smooth muscle) * Increased specificity --> Decreased Side Effect Effects: - Inhibit contraction of the prostate smooth muscle - Inhibit contraction of bladder internal sphincter - Littel effect on blood pressure Clinical uses: Benign Prostatic hyperplasia Adverse effects: Orthostatic hypotension/syncope: not as severe for tamsulosin compared to other alpha-antagonists (bc its increased specificity to the prostate

Alpha-hemolytic streptococci

S. Pneumoniae - optochin susceptible - bile-soluble - diplococci - no lancefield antigen - can be part of normal pharyngeal flora ** does not live in GI so it does NOT have any bile resistance Viridans streptococci - optochin resistant - bile resistant - normal oral flora - S. mitis important example - various lancefield groups ** in mouth and GI so resistant to bile

In order to grow fungi in the lab- which medium can be used?

Sabourad's Medium (ONLY used to grow fungi!) - The acidic pH (5.6) of traditional sabouraud agar inhibits bacterial growth - Fungi are slow growing - Consider the source of the sample. Without something in the media to inhibit the growth of bacteria, you may never see the fungus - Culture may not be ideal

What is dysplasia?

Seen on epithelial surfaces, ex. in the uterine cervix Dysplasia: expansion of immature epithelial cells - Syn: intraepithelial neoplasia - A preneoplastic condition, rather than a true neoplasia - Potentially reversible, if an initiating stimulus is withdrawn - May progress to carcinoma Morphology: - Gross appearance: not changes - Special techniques may apply for identification, ex. colposcopy **** Microscopic identification: look for loss in uniformity of the individual cells and loss of their architectural orientation ****

List the Properties of Specific Beta antagonists (selective, nonselective, and Nonselective/alpha1)

Selective (beta1 only): - Atenolol (beta 1) - Esmolol (beta1- short acting- half-life=10min*) - Metoprolol (beta1, local anesthetic action) Nonselective (beta1, beta2) - Propranolol: local anesthetic action - Pindolol: partial agonist activity(HR wont go too low) and has local anesthetic action - Timolol: NOO local anesthetic action Nonslective/alpha1 (beta1, beta2, alpha1): - Labetalol: partial agonist (HR doesnt go to low, and local anesthetic action) - Carvedilol

Describe the structure and function of Pili/Fimbriae in bacteria

Short PROTEIN strands, all over cell surface Functions: - Adhesion to host cell receptors (ex. P-pili in uropathogenic E.coli) - Twitching motility (only a fe species, ex. Neisseria; Type IV pili) - Conjugation (specifically F-pilus) - Occasionally antiphagocytic - Often undergo antigenic variation

Eosin Methylene Blue agar (EMB)

Similar in principle to MacConkey agar, except different indicators (eosin and methylene blue) that inhibit gram-positive organisms and change color with pH - lactose-fermenters appear as blue-black colonies, while non-fermenters appear clear - organisms that are strong lactose fermenters, such as E.coli, can have a shiny green metallic sheen

What are Bacteria (Prokaryotes)?

Single cell organisms with BOTH DNA and RNA, but NO defined nucleus - double stranded DNA organized into a circular chromosome- nucleoid - some carry plasmids- small DNA molecule that is separate from chromosomal DNA - Most posses a cell wall which contains peptidoglycan (basis of MOST staining) - Size from 0.1-10micrometers - Posses 70S ribosomes **** this is what makes antibiotics different from us (comprised of 50S and 30S subunits, frequent drug targets)

Staging Cancers

Stage of cancer is an evaluation of: - size of a primary lesion - its extension to adjacent organs/tissues - spread to regional lymph nodes - presence/absence of distant metastases Staging has a greater clinical value than grading in terms of: - prognosis and - selection of the best form of therapy Major Staging Systems: TNM system (Tumor, lymph Node, distant Metastases) develpoed by UICC (Union Internationale contre le Cancer) - T1, T2, T3, and T4 respectively describe the increasing size of the primary lesion - N0, N1, N2, and N3 indicate progressively advancing lymph node involvement - M0 and M1 reflect the absence or presence of distant metastases Ex: T1N0M0, T2N1M1 AJC(C) system (American Joint Comittee for Cancer) Divides cancers into stages 0-IV * lymph node involvement and distant metastases= Stage IV

Case-Control studies (CSS)

Starts with disease in the PRESENT - recruits comparable cases (with disease) and controls (with no disease) compares cases and controls on past exposure to a possible risk factor for the disease *** Retrospective design*** (looking in the PAST) - Good for studying rare diseases Statistical measure: Odds ratio Ex: Interpretation: The odds of a shipyard worker exposed to asbestos getting lung cancer is 13 times that of a shipyard worker who was not exposed to asbestors This is an alternative observational design to identify risk factors for a disease/outcome Q's: - how do diseased cases differ from non-diseased (controls) with respect to prior exposure history? - compare frequency of exposure among cases and controls - Effect--> cause - CANNOT calculate disease INCIDENCE rates bc the CCS does NOT follow a disease free-population over time Population at risk --> Controls (exposed/unexposed) and Cases (exposed/unexposed) Present --> Past

Alpha1 effects on organs

Sympathetic - Contract sphincters in GI tract - Contract smooth muscle in bladder, detrusor - Contract uterus - Ejaculation from penis - glyogenolysis and gluconeogenesis in liver

Alpha2 effect on organs

Sympathetic - Relaxes smooth muscle in GI tract - Decreases decretion in GI tract - Aggregation of platelets

Beta2 effects on organs

Sympathetic - Relaxes smooth muscle in lung, GI tract, bladder, detrusor - Glycogenolysis and gluconeogenesis in liver - Inhibit degranulation in mast cell

What is transcription?

Synthesis of an RNA copy of a gene or set of genes (operon) 3 primary types of RNA: - mRNA: carries coded instructions for protein synthesis - tRNA: carries specific AA to ribosomes during protein assembly - rRNA: part of the composition of the ribosome

How is humoral response regulated?

T reg cells are believed to be involved in down-regulating the response - Treg cells are characterized bt expression of CD4, CD25, and Foxp3 - they are stimulated by antigen but instead of releasing cytokines produced by otehr subsets (such as those produced by Th1, Th2, and Th17 cells) that may activate other cells, T reg cells release inhibitory factors such as TGF-beta and IL-10 that supress immune responses, including B-cell response - this fx may be of importance in immune response regulation and control of autoimmune disease Antibody may also reg. B-cell response via a neg feedback loop- the removal of blood from an immunized animal can stimulate antibody production. Passive transfer of antibody can suppress antibody formation to a specific antigen Passive antibody can bind or block (intercept) antigen and prevent binding to receptors on cells such as T and B-cells

What genes are affected in the evasion of apoptosis?

TP53 or Members of BCL-2 family Result: inhibition of apoptosis Significance: tumors with predominantly inhibited apoptosis (opposite to increased proliferation) are more resistant to anti-neoplastic therapy Intrinsic: Stress, radiation, chemicals--> DNA DAMAGE--> p53 response--> BAX/BAK--> incrreased BCL-2, BCL-XL, MCL-1 --> Cytochrome C and APAF-1--> caspase 9--> capspase 3--> death substrate --> Apoptosis Extrinsic: FasL + FasD--> Procaspase 8--> Caspase 8--> BID--> BAX/BAK to enter intrinsice path or from Caspase 8--> Caspase 3--> death substrate--> Apoptosis

Antimuscarinic drugs include

Tertiary amines and Quaternary Ammonium Compounds Tertiary amines: - Atropine *** This is a prototypical drug, know it well! - Scopolamine - Solifenacin Quaternary Ammonium Compounds: - Glycopyrrolate - Ipratropium

What is meant by active transport being driven by hydrolysis of ATP?

That it is energy dependent: the drug moves AGAINST a concentration gradient - This is a specialized process requiring a carrier; the carrier molecule may be highly selective for the drug molecule - Competitive: drugs of similar structure may compete for sites of absorption on the carrier - Saturation may occur bc only a fixed number of carrier molecules are available Two types: 1. Primary: energy for transport is derived DIRECTLY from the breakdown of some high-energy phosphate compone (i.e. ATP) 2. Secondary: When the energy for transport is derived from energy that has been stored in the form of ionic concentration differences between the two sides of the membrane NOTE: both facilitated and active transport use carriers

Describe the replication for Retroviruses

The (+)ssRNA is first reverse transcribed by virally encoded reverse transcriptase carried by virus upon penetration - product of reverse transcription= dsDNA, and that DNA that gets integrated into the hosts genome via another virally-encoded enzyme, an integrase The integrated viral DNA is referred to as provirus (analogous to the prophages of bacteriophages) - when the regulatory sequences controlling the provirus get activated, cellular DNA-dep RNA pol (RNA pol II) transcribe the DNA into mRNA - Again, some of the RNA will go into protein synthesis, whereas the rest will be used as genomic RNA to be packaged into new virions

Describe Host specificity (tropism)

The cells/ tissues/ organisms that will be affected by a virus are determined by: 1. Host cell susceptibility: - possesses surface receptors/co-receptors allowing viral attachment - "cell CAN be infected: 2. Host cell permissiveness: - contains all components required for virion production (i.e. leads to a productive infection - "cell ALLOWS replication" *** Virus needs BOTH susceptibility and permissiveness to propagate

What are two major pathways in the synthesis of eicosanoids from arachidonic acid?

The cyclooxygenase and lipoxygenase pathway ** Eicosanoids are physiologically and pharmacologically active compounds - Lipoxygenases make: HETEs, Leukotrienes, Lipoxins - Cyclooxygenases make: prostalgnadins, prostacyclin, and thromboxane (which are prostanoids) *** Prostanoids are mediators of pain, fever, and inflammation

What is metaplasia?

The replacement of one adult cell type by another adult cell type - Within the same germ layer - Reversible Goal: proliferating new cells will be able to withstand an action of a harmful stimulus (Ex: Smoking --> Metaplasia of columnar to stratified squamous epithelium) Significance: Epithelial metaplasia--> can be the backgroud for malignant transformation (may be the first or second seen leading to cancerous growth)

What are the two primary determinants of infectious disease outcome?

The status of the host immunity and the virulence properties of the pathogen - if the host is stronger it can kick the microbe out - if the microbe is stronger then the host will take longer to improve (stay longer in the disease state)

Epstein-Barr Virus (EBV)

The ultimate B-lymphocyte parasite - was discovered by electon-microscopic observation of characteristic herpes virions in biopsy specimens of a B-cell neoplasm, African Burkitt lymphoma (AfBL) ** Association with infectious mononucleosis was found accidentally when serum from lab tech convalesing from infectious mono was found to contain the antibody that recognized AfBL cells

Differentiate between therapeutic index and window

Therapeutic index: ratio between a median harmful dose and a median effective dose of a drug - Ex: LD50/ED50 ; TD50/ED50 Therapeutic window: RANGE between minimum therapeutic dose (or plasma concentration) and the minimum toxic dose (or plasma concentration) of a drug - this is the range of doses that have the highest probability of therapeutic success

Describe the Latent Cycle in Herpesvirus Replication

There are NO common strategies!- different herpesviruses establish latency through different means Alphaherpesvirinae: - generally establish latency in sensory ganlia (neurons) **Latent cycle is in neuron soma: - Fusion at axonal termini - Retrograde axonal transport to nucleus - Expression of alpha, beta, gamma genes, as well as LAT RNAs during the first 24-72hrs of neuronal infection - Strong CD8 T lymphocyte response in CNS 5-7 dpi (with contributions by infiltrating macrophages and gammadelta T cells; microglia seem to have a limited protective effect) - Decrease in viral replication - Silencing of lytic gene expression (deacytylation of histones associated with lyic genes) Repression of lytic cycle: - Neuronal respressors of alpha genes - Hormonal repression of viral gene expression (nerve growth factor, NGF) - Lack of viral and cellular factors requires for overcoming host silencing and allow alpha gene expression - High level of LAT (latency associated transcript) expression: viral RNA-mediated repression of alpha gene expression - microRNAs (LAT-derived): down-regulation of lytic gene products Episomal persistence of viral circular DNA associated with nucleosomes (chromatin silencing) Betaherpesvirinae: - can establish latency in many different tissues Gammaherpesvirina: - Generally estabish latency in lymphoid tissue (B and T cells)

Adverse effects of Cholinesterase Inhibitors (predicatble- actions of acetylcholine)

They are the same as those of direct acting cholinergic agonists. In addition fatigue, muscle cramps, and fasciculation also can occur Another thing to note; cholinesterase inhibitors DO NOT have significant actions at sites that are NOT innervated by cholinergic neurons (ex. blood vessels) - direct acting muscarinic agonists will dilate blood vessels (M3-mediated nitric oxide release in the vascular endothelium) - cholinesterase inhibitors will not dilate blood vessels (this makes sense if you think about the location/highest concentration of acetylcholinesterase)

Describe maturation of a virus

This is processing of viral components (virus- or host-derived) required to move from a non-infectious to an infectious state (i.e. a virion) - occurs late in assembly or after particle release - can be concomitant with assemly - needs virally-encoded enzymes - proteolytic or glycosidic processing - can be target of antiviral agents

What are four major mechanisms of gene transfer?

Transformation: uptake of naked DNA Transduction: infection by a nonlethal virus carrying bacterial genes Conjugation: plasmid mediated exchange of information between bacteria in contact Transposition: exchange of genetic information via mobile genetic elements

Grading of tumors

Tumors of LOW GRADE (grade 1): - grow more slowly - penetrate adjacent tissue less actively - metastasize more rarely Tumors of HIGH GRADE (grade 3): - grow more rapidly - more often invade adjacent tissue - metastasize more frequently **Well-differentiated (low-grade) tumors often transform into poorly-differentiated (high-grade) - much more rarely, a tumor becomes more differentiated **** BOTH low- and high-grade malignant tumors are cancers with the ability to metastasize ***

Making the choice of which test to use?

Two variables (independent data): - Chi-square (X^2) - Fishers exact test - Pearson product-moment correlation - Student or independent t-test - one- way analysis of variance (ANOVA) More variables (independent data): - 2 way analysis of vairance (ANOVA) - Regression 2 variables (dependent data): paired t test More than 2 variables: repeated measures (dependent data

Spectrum of UV light

UVA: not harmful UVB: carcinogenic*** UVC: very carcinogenic, filtered out by ozone shield Skin Cancer (3 major types): - Squamous cell carcinoma - Basal cell carcinoma - Melanoma Xeroderma pigmentosum (insufficiency in DNA repair mechanisms)--> 2000-fold increased risk of skin cancer Mechanism of Carcinogenicity with UV light: Formation of pyrimidine dimers (thymine-thymine, thymine-cytosine or cytosine-cytosine)---> Formation of cyclobutane rings with distortion of phosphodiester backbone of the double helix --> Activation with subsequent exhaustion of nucleotide excision repair mechanisms --> Accumulation of mutations with neoplastic transformation

MOA of folate antagonists

Ultimate effect of sulfonamides ALONE, or if trimethoprim ALONE is mainly BACTERIOSTATIC Ultimate effect of sulfonamides + trimethoprim is mainly BACTERICIDAL Sulfamethoxazole + trimethoprime is a VERY common agent

What are the features of the antibacterial effect of Aminoglycosides?

Ultimate effect= BACTERICIDAL Bacterial killing is concentration-dependent (increasing concentrations kill an increasing proprotion of bacteria at faster rate) A significant postantibiotic effect is present (antibacterial activity persists several hrs beyond the time that measurable drug is present) **Bc of the latter two properties a given total amt of aminoglycoside may have better efficacy and lower toxicity when administered as higher single daily dose, than when given as lower thrice-daily doses

Which drug diffuses readily across lipid cell membranes: the ionized or un-ionized form?

Un-ionized drug diffuses readily across lipid cell membranes - For weak acid, the un-ionized HA readily crosses the membrane - For weak bases, the un-ionized B readily crosses the membrane

Transference

Unconscious organizing activity - pt unconsciously deposits feelings/attitudes from past relationships/situations onto presnt - qualities of past relationships are attributed to the doctor Ex: 48yo female pt is convinced you are withholding vital medical info from him and thus resents you bc he had a emotionally distant and secretive mother

Immunoblotting

Used for COMPLEX antigens - Complex proteins must first be separated in a gel - In SDS-PAGE, sodium dodecyl sulfate polyacrylamide gel electropheresis, the protein is solubilized in SDS and is separated into fractions by PAGE - The fractions migrate according to molecular size (smallest migrating fastest) - The separated proteins are then transferred electrophoretically, "blotted", to a nitrocellulose membrane - The antigen is reacted with antibody and an indicator system is added to detect the bound antibody as a colored band - Protein, DNA, and RNA antigens can be analyzed by immunoblotting - Geographical motifs are used to describe the methods used for diff types of antigen (ie. Western blot for protein, Northern blot for RNA and Southern blot for DNA) Steps: - SDS Polyacrylamide Gel Electrophoresis - Protein Blot on Nitrocellulose - Label with Specific Antibody - Detect Antibody (revels protein of interest) NOTE: - Western blot may be used for confirmation of presence of HIV antibody in serum - HIV antigens are separated on a blot and are then reacted with human serum to detect antibodies to principal HIV glycoproteins

Latex Agglutination (aka latex immunoagglutination assay)

Used in the diagnosis of bacterial, fungal, parasitic and viral infections - It is also applicable for cancer detection and for identification of other substances such as hormones, drugs, and serum proteins Agglutination rx involved: - In vitro aggregation of microscopic carrier particles, called latex--> this aggregation is mediated by specific rx between antibody and antigen, one of which is immobilized on the surface of latex particles - Thus- latex agglutination may be used to detect antigen or antibody - These assays are simple, rapid, do not involve the use of any hazardous materials and may be performed on variety of samples such as saliva, blood, urine, or cerebrospinal fluid May be performed as a DIRECT test--> to detect antigen - antibody is adsorbed to latex beads and agglutination occurs when the beads are mixed with a sample containing specific antigen May be performed as an INDIRECT test--> to detect antibody - Antigen is adsorbed to the beads and agglutination occurs when the beads are mixed with a sample containing specific antibody

Chromogenic agars

Usually designed to differentiate organisms of interest though a change in colony color - these have been developed to identify specific species, such as Listeria monocytogenes or Staphylococcus aureus (SA), or to identiy specific phenotypes such as methicillin-resistant SA (MRSA) vs. methicillin-sensitive SA (MSSA) - they are specific and quicker as growth can be easily seen

A pt with marked CP for 4 hrs and elecated serum creatine kinase- angiogram reveals a complete blockage of left circumflex artery 2 cm from its origin- which substance would you most expect to be elaborated around the region of tissue damage in 3 days as an initial response to increase myocardial function and promote healing?

VEGF (vascular endothelial growth factor)

What is the normal function of VHL protein?

VHL protein forms a complex with ubiquitin-ligase involved in degradation of HIFs (hypoxia-inducible factors) - In hypoxic environment, VHL is inactivated, and HIFs stimulate transcription of VEGF, PDGF, FGF, GLUT1, etc. to withstand hypoxia Loss-of-function mutation in VHL prevents degradation of HIF-1a --> angiogenesis and cell growth (allows tumor growth) ** Neoplasia will die without proper blood supply

Drugs that are used to increase BP and MAP by vasoconstriction, increases systemic vascular resistance are referred to as

Vasopressors (increase BP and force of Heart) - some are inotropes and are used to improve cardiac output - If intravascular volume status has been optimized with volume resuscitation but hypotension and inadequate tissue perfusion persist then vasopressors are indicated - vasopressor use must be tailored to the physiologic disturbence (need to identify the kind of shock) Use of vasopressors effectively depends on knowing the: - receptor selectivity of the various drugs - receptor selectivity may be dose-dependent

After a gram stain you find the bacteria is gram-negative bacilli with curved and spiral rods (motile) and is a facultative anaerobe- which bacteria may it be

Vibrio sp. - comma-shaped rods - oxidase (+) - alkalophile - motile - likes/may need salt

A pt presents with yellowish appearance, scleral icterus, and mild right upper quadrant tenderness- what could the icterus be due to?

Viral hepatitis

Describe Assembly (envelopment) of a virus

Viral proteins translated and trafficked to a host membrane - virus nucleocapsid/capsid buds through membrane - membrnae envelopes capsid - envelope source can influence pathogenesis Simultaneous: - capsid forms as viral particle is budding through membrane Sequential: - capsid forms, accessory proteins and envelope added in step-wise fashion (this ex also has intermediate steps, but some do not)

Compare and contrast the medically important Microbial Pathogens

Viruses - No cells - 0.002-0.2 micrometers - DNA or RNA - No nucleus - No Ribosomes or Mitochondria - Outer surface= protein capsid and lipoprotein envelope - No motility - No binary fission replication Bacteria - Has cells - 1-5 micrometers - DNA AND RNA - Prokaryotic nucleus - 70S ribosome - NO mitochondria - Outer surface= rigid wall with peptidoglycan - Some motility - Binary fission Fungi - Has cells - 3-10 micrometers (yeasts) - DNA AND RNA - Eukaryotic nucleus - 80S ribosome - Mitochondria present - Outer surface= rigid wall with chitin - No motility - Replication= budding or mitosis Parasites (Protozoa and Helminths) - Has cells - 12-25 micrometers - DNA AND RNA - Eukaryotic nucleus - 80S ribosome - Mitochondria present - Outer surface= flexible membrane - Has the MOST motility - Replication= mitosis

Many drugs act as ____, such as weak acids and bases

Weak electrolytes - these are only PARTIALLY IONIZED when dissolved in water Extent of ionization influences the drugs diffusional permeability: - Ionized species of drug contains a charge and is more water soluble - NONionized species of drug is more lipid soluble Extent of ionization of a weak electrolyte will depend on both the pKa of the drug and the pH of the medium in which the drug is disssolved - lower pKa of drug= more acidic - higher pKa of drug= more basic

First pass effect

When a drug is absorbed from GI, it enters the portal circulation, which takes it to liver, before entering the systemic circulation. From there, the drug is delivered to all tissues - First pass effect occurs if the drug is rapidly metabolized in the liver or gut wall during this initial passage - Routes of administration that AVOID first-pass effect= sublingual, transdermal, parenteral * A drug that has a high first pass effect will have a LOW bioavailability (low first pass effect will lead to a high F) Ex: Nitroglycerin has a significant first pass effect. Oral doses of nitroglycerin have been show to be less than 1% bioavailable As a result, nitroglycerin is formulated for pts as a sublingual preparation (administered under the tongue)- Othere routes, which bypass first pass metabolism (IV) are also used for nitroglycerin administration

Monoclonality

Within a neoplasm, all tumor cells originate from a single precursor cell, i.e. all tumors are (mono)clonal** Markers of monoclonality: X-linked markers - G-6-PD - Human androgen receptor gene (HUMARA) Polyclonal proliferation (hyperplasia) is always NON-NEOPLASTIC - If a true tumor has 2 tissue components, one had to be monoclonal, another one can be polyclonal Ex: breast fibroadenoma, a stromal tumor with glandular component being polyclonal

Basic structural forms of fungi include

Yeasts: with buds that grow off into big balls and Filamentous fungi --> Septate Hyphae (cross wall= sepatate) or Aseptate Hyphae - Conidiophore with conidia can be seen branching off at the end of the hyphae that cause further infection Septate Hyphae: - characterized by cross walls - generally have a more uniform width (more like pipes with interior crosswalls not disrupting the outer structure) * Most medically important hyphal fungi have cross walls Aseptate Hyphae (AKA nonseptate or coenocytic): - hollow and multinucleate - may be of irregular width - rapid growth: serious opportunists, may be fatal overnight - NOT common mycoses (fungal infection in humans- these are not mycoses bc usually once infected the pt will die overnight) Mycelium (A mat of hyphae) - When mold grows on fruit, for ex, the mycelium is the fluffy substance that resembles cotton

Name two drugs that are used to treat bacterial infections

Zithromax- 52.6 million prescriptions and Amoxicillin- 52.3 million prescriptions

Medical Documentation

a form of communication within a healthcare system - creates continuity in pt care - allows provider to make his/her thinking process and management plan clear to every other provider - can provide a longitudinal picture of a persons health over time, including the nature and evolution of disease processes - can be a source of data for future research (i.e. electronic medical records) NOTE: - 80% of diagnoses are made on history alone - H&P contains concise and detailed information - outlines a plan - communicating info to all providers involved in care of ot - an important medico-legal document H&P structure: History: - record pts pertinent medical history from birth to present - CC, HPI, PMH, FH, SH, and ROS PE: - Document a currrent and thorough (head to toe) physical exam - Include known, relevant lab and imaging results Assessment: - Identify/localize abnormal findings - Interpret findings and make hypothesis about the nature of pts problem - differential diagnosis - generate problem list with chief complaint and active problems first Plan: - include evaluation and/or management for each problem, as needed

African Burkitt Lymphoma (AfBL)

a poorly differentiated monoclonal B-cell lymphoma of the jaw and face that is endemic in children living in the malarial regions of Africa - EBV infection facilitates the survival of cell that undergo a chromosomal translocation that juxtaposes the c-MYC oncogene to a very active promoter, such as na Ig gene promoter [t(8;14), t(8;22), t(8;2)] to allow tumore growth BUrkitt tumors contian - EBV DNA sequences but express only the EBNA-1 viral antigen - tumor cells are also relatively invisible to immune control ** Malaria may enhance development of AfBL by promoting the proliferation of EBV-bearing memory B cells ** tumor cells of burkitt lymphoma are derived from lymphocytes PCR and DNA probe analyiss for the viral genome and amt of virus (virus load) and immunofluorescent idenitifaction of viral antigens are used to detect and follow the course of infection

Neoplasia

a process of uncontrolled growth (=accumulation) of cells due to: - porliferation and/or - evasion of apoptosis Neoplasm: a mass of cells, which grow without host control - tumor: a neoplasm, which can be recognized as a distinct lump or lesion * In clinical practice the terms "neoplasm" and "tumor" are used as synonyms Benign (innocent) tumores are slow-growing, innocuous tumors, that usually are of littel consequence to the host Malignant tumors (cancers) have more rapid growth rate, invade and destroy adjacent tissues, CAN METASTISIZE (seed and grow at distant sites) and are fatal (if left untreated) Intermediate (locally malignant) tumors are locally invasive (therefore not benign), but do NOT have tendency to metastisize (therefore not malignant) Carcinoma in situ is a pre-invasive cell proliferation (a type of severe dysplasia, NOT a cancer) that has cytological features of malignancy

In many cases susceptibility of a microorganism to specific antibiotic serves as a guide in choosing antimicrobial chemotherapy- Measurement of antimicrobial activity is done by dilution method and leads to the following measures:

a) Minimum inhibitory concentration (MIC): the lowest conc. of antibiotic that inhibits growth of tested bacteria b) Minimum bactericidal concentration (MBC): the lowest concentration of antibiotic that KILLS the tested bacteria

Transcriptionist

allied health professional who converted voice-recorded reports dictated by physicians into text Speech-recognition software: has become sophisticated and automated, but errors do occur NOTE: over 12% of veterans received telehealth services in 2016 Policies for telehealth at 2016 AMA Annual meeting: - disclose financial or other interests in applications or services - protect pt privacy/confidentiality - inform pts about limitations of the relationship and services and take steps to overcome them (ex. have another healthcare professional at pts location conduct an exam or obtain vital info through remote technologies) - coordinate care between PCP and only health consultation Highest use for telehealth in pt interactions: radiology (40%), psychiatry (28%), cardiology (24%) HIghest use for interactions with health care specialist: emergency med (39%), pathology (30%), radiology (26%) - videoconferencing most widely used - more often in larger medical practices/ hospital settings

Drug accumulation occurs if

another dose of a drug is given before the previous dose is completely eliminated - Drug accumulation therefore occurs with repetitive (or multiple doses) - If the dosing interval is shorter than the half life of the drug, there will be a larger residual amount of the drug in the body (i.e. more drug accumulaiton) * If a drug has a very short half-life (which is less than the dosing interval), then accumulation will NOT occur bc the plasma concentration resulting from each dose will be the same as the dose alone. Ex: - If a single dose of a drug is given the drug conc. will gradually fall to 0 (when the drug is completely eliminated) - If multiple doses are given, there will be accumulation of the drug (as the drug will not be completely eliminated from the body) *** After repetitive doses, steady state will be achieved (3-5 t1/2)

Regression

anxiety-evading mechanism - personality may suffer a loss of some of the development already attained and may rever to a lower level of adaptation and expression

Identification/introjection

assuming the characteristics, qualities or traits of another person or group

Bacteria replicate by

binary fission 1. Single bacteria with 1 chromosome (replicates and creates a perfect duplicate) 2. Chromosome begins DNA replication 3. Single bacteria with 2 chromosomes attached to cell membrane. Septum begins to form 4. Cells divide at septum ** 2 cells originating from 1 that are identical to one another--> entire population from single cell= identical --> mutations can lead to different more advantaged which will grow further and then the disadvantaged will go away

Full agonist, partial agonist, antagonist and inverse agonist ALL

bind to the receptor/target - they bind with differing affinity (different KD concentrations) and then we cant tell which curve belongs to which drug. In other words, a drug can have high affinity for the receptor but have high, low, zero, or negative efficacy These 4 drugs also all have different intrinsic activity - which is the ability of drug to activate the receptor to produce a response - this is similar to efficacy, but intrinsic activity refers just to the drug-receptor complex, whereas efficacy refers to the drug-receptor-downstream actions-final response

Vancomycin MOA

binds to the terminus of nascent peptidoglycan pentapeptide- the binding inhibits transglycosylase, the enzyme that catalyzed the elongation of PG chain--> this prevents the formation of linear peptidoglycan chains ***The binding also inhibits transpeptidase (like beta-lactams), but since transglycosylation precedes transpeptidation, inhibition of transglycosylase is the primary mechanism of action of the drug **Ultimate effect is BACTERICIDAL

Diphyllobothrium latum (new name= Dibothriocephalus latus)

broad or fish tapeworm - very BIG (can be as big as 30ft) - follows ingestion of raw fish - intestinal disease Complication: Megaloblastic anemia (bc it loves B12)

Only so much nucleic acid can fit into a

capsid - this limitation drived efficient use of nuclic acid (examples below) ** Some diagnostic tests make use of these properties Assembly Release Maturation

Ionizing Radiation- mostly effects

cells in S- and G2-phase of the cell cycle Ex (mainly historical): Survivors of atomic blasts - X- and gamma-rays--> myeloid leukemias - Iodine--> thyroid carcinoma - Strontium--> osteosarcoma Minors (uranium and radon)--> lung carcinoma Pts after head and neck radiotherapy--> thyroid carcinoma Steps of Ionizing Radiation-Induced Carcinogenesis: Ionizing radiation (all types)--> water radiolysis --> formation of free radicals (OH. + H.) ---> Double-strand DNA breaks**, translocations, and point mutations

Initiators

chemical carcinogens Types of: Direct initiators: - Highly reactive electrophils (contain electron-deficient atom)-- react with nucleophilic sites (electron-rich) with DNA as the most important target Major group: alkylating agents: - Chemotherapeutic drugs: nitrosourea (s) - *Induced secondary cancer: leukemia Indirect initiators: Converted to ULTIMATE carcinogens (act as direct) by cytochrome P-450-dependent monooxygenases or other enzymes - Ultimate carcinogens are capable to intiation and act as direct carcinogens These include: - Polycyclic hydrocarbons-- benzanthracene, benzopyrene, etc. - Nitrosoamines and nitrosoamides - Aflatoxin B1 - Alkylating chemotherapeutic drugs that require metabolic activation-- Cyclophosphamied, chlorambucil, etc. - Chemicals (Benzene, Arsenic, Cadmium, Urenium etc.) Affected genes: RAS, TP53, etc.

Parasympathetc NS

conserves energy and maintains organ function -Activation of the PSNS slows heart rate, lowers BP, stimulates GI movements and secretions, empties the urinary bladder and rectum and protects the retina from excessive light

DNA gyrase and topoisomerase IV (both type II topoisomerases), ___ DNA

cut DNA, rotate cut ends (relaxation; relieve supercoiling by introducing negative supercoilds; rejoining) - Allows unwinding to proceed, regulatory mechanism (speed) - Topo IV also decatenates, or unlinks the replicated DNA molecules

Passive Aggression

demonstrating hostile feelins in a nonconfrontational manner; showing indirect opposition

The effective dose of a drug may vary with the

dosage form and the route of administration - Drugs administered IV enter the blood stream directly and completely - Varying rates and degrees of absorption can occur with drug administration via different routes Common routes include: - oral - sublingual - rectal - parenteral: ex. IV, IM, SC - topical - transdermal - inhalation

Cancers induce a local chronic inflammatory reaction with

doubtful beneficial, but obvious malicious effects - secretion of growth-promoting factors, ex. EGF - inactivation of growth-inhibiting factors - induction of angiogenesis via VEGF and bFGF - induction of invasive growth and metastases via proteases released from macrophages - inhibition of immune destruction via TGF-beta and type 2 macrophages

Exanthem subitum, or roseola is caused by

either HHV-6B or HHV-7 and is one of the 5 classic childhood exanthems - Characterized by the rapid onset of high fever of a few days duration, which is followed by a rash on the trunk and face, and then it spreads and lasts only 24-48 hrs * presence of infected T cells or activation of delayed-type hypersensitivity T cells in skin may be the cause of the rash * disease is effectively controlled and resolved by cell-mediated immunity, but the virus establishes a lifelong latent infection of T cells ** Although usually benign, HHV-6 is the most common cause of febrile seizures in childhood (age 6-24 months) HHV-6 may also cause: - mono syndrome and lymphadenopathy in adults and may be cofactor in pathogenesis of AIDS - similar to CMV, it may reactivate in transplant pts and contribute to failure of the gradt - also associated with multiple sclerosis and chronic fatigue syndrome ** In apprx- 1% of individuals in US and UK, HHV-6 is integrated into the telomeres of every chromosomes and can be genetically transmitted to offspring --- the virus may be reactivated by certain drugs (including antibiotics and steroids), produce virus, and may cause fatigue, cognitive dysfunction and other problems

mecA

encodes an altered penicillin binding protein that is proficient for cell wall synthesis but is not inhibited by beta-lactam antibiotics or cephalosporins - mecA allows a bacterium to be resistance to antibiotics such as methicillin, penicillin, and other penicillin-like antibiotics Ex: mecA+ MRSA that was resistant to beta-lactam antibiotics, but susceptible to other antibiotics - this supports horizontal gene transfer of mecA DNA (bc some can be mecA-)

Tanners staging of puberty (* in most cases puberty is complete by 16yr)

females: I: preadolescent ii: breast bud III. areolar diameter enlarges IV. secondary mound; sep of contours V. mature female males: I. childhood size II. enlargment of scrotum/testes III. penis grows in length, testes continue to enlarger IV. Penis grows in lenght/breadth; scrotum darkens, testes enlarge V. adult shape/size Pubic hair in both: I. none II. sparse, long straight "downey" III. darker, curling increased amt IV. coarse, curly adult type V. adult, extends to thigh

Pasterurization is most often used for

food/beverages (milk, juice, eggs) Two processes: - "Normal": 72*C for 15-20s- kills most pathogens, reduces bacterial loads; stable 2-3 weeks if kept cold - "Ultrapasturization", UHT (ultra-high temp): 135*C for 2s-- will kill spores; it aseptic packaging, stable 6-9 mo at RT

Although most CMV infections acquired in young adulthood are asymptomatic, pts may show a

heterophile-negative mononucleosis syndrome - sxs of CMV disease are similar to those of EBV infection but with less severe pharyngitis and lymhadenopathy - heterophile antibody is NOT present (unlike EBV where it is present) CMV should be suspected in pt who has heterophile-neg mono or in whom there asre sings of hepatitis but results of tests for hepatitis A, B, and C are negative

To establish disease, virus must overcome both

host defenses and cause damage to the host Successful infection of a host requires: 1. Minimal virus inoculum: - Virions are often dilutes (ex. air, water) and transferred under adverse conditions (ex. heat, cold, pH, osmotic shock, UVs) --> viruses replicate fast and in large numbers to increase the likelihood of transmission 2. Host accessibility, susceptibility and permisiveness - Target tissue, specific receptors, cellular machinery req. to support the replication cycle--> also determines which hosts get infected, tissue tropism, and the diseases caused 3. Weakens antiviral defenses: effective, physical/chemical defenses, cellular defenses, innate and adaptive defenses normally prevent infection

How is the influx of calcium related to cell injury?

increase cytosolic calcium works to increase the activation of cellular enzymes. Ex: - Phospholipases decrease phospholipids and proteases induce disruption of membrane and cytoskeletal proteins --> membrane damage - Endonucleases--> nuclear damage - ATPase--> decreased ATP as does the increase in mitochondrial permeability transition that is also caused by increase cytosolic calcium

Cytomegalovirus (CMV)

infects apprx 1% of all newborns and at least 50-80% of adults by age 40 - it is the most common viral cuase of congenital defects ** CMV is particularly important as an opportunistic pathogen in immunocompromised pts * member of hetaherpesvirinae - CMV carries specific mRNAs into the cell in the virion particle to facilitate infection Human CMV replicates only in human cells Pathogeneiss is similar to other herpesviruses CMV is.. - acquired from blood, tissue, and most body secretions - causes productive infection of epithelial and other cells - establishes latency in T cells, macrophages and other cells - Cell-mediated immunity is req. for resolution and maintenance of latency and contributes to symptoms - role of antibody is limited - suppression of cell-mediated immunity allows recurrence and severe disease - CMV generally causes subclinical infection

MOA of Daptomycin

inserts into the CELL MEMBRANE in a phosphatidylglycerol-dependent fashion, where it then aggregates - alters the curvature of the membrane, which creates holes that leak ions--> results in bacterial cell death ** Gram positive coverage only - Resistnance mechanism: unkown

Hummoral Immune Response

involved activation of B-cell proliferation and differentiation and prod and secretion of antibody - B- cells usually req. T-cell help (more specifically, Tfh cells) for antibody production and hte process is reg by several factors - Antibodies perform number of importatnt fx in body and presence can be demonstrated by variety of techniques many of which are used routinely in med lab

Pheochromocytoma

is a catecholamine (dopamine, epinephrine and norepinephrin) producing tumor Pts usually present with palpations (beta1), headache (due to increase BP), and produce sweating. The domonint sign of the diseases is hypertension (increased heart rate, alpha1 constriction of vessels) Usually treated with surgery- Drugs are used for treatment while the pt waits for surfery or if the tumor is inoperable How would you target the sympathetic nervous system to target the disease? alpha1, alpha2, beta1, beta2 (treate with blocking alpha first - bc pure alpha stimulation has a strong affect) - Block alpha and beta receptors - Or make less neurotransmitter with Metyrosine

MOA of Aspirin

it is a weak organic acid that IRREVERSIBLY acetylates and, thus, inactivates cyclooxygenase (the other NSAIDs are reversible inhibitors of cyclooxygenase) Mature platelets express only COX-1, TxA2 (the major product of COX-1 in platelets) it induces platelet aggregation and amplidies the signal for other, more potent platelet agonists such as thrombin and ADP Asipirin IRREVERSIBLY inhibits COX-1-mediated production of TXA2, thereby reducing it- mediated vasoconstriction and platelet aggregation and the subsequent risk of cardiovascular events - Since aspirin irreversibly inhibits platelet COX, its antiplatelet effect lasts 8-10 days (the life of the platelet) ** Onsly aspirin is the NSAID that can be used for cardiac protection because of its IRREVERSIBLE binding

Cell membranes are composed of a phospholipid bilary- this lipid membrane allows ____ drugs to pass through

lipophilic drugs (with small MW) - Drugs diffuse from a region of high concentration --> low concentration (passive and non-selective process) Ficks Law: the concentration gradient, membrane surface area and thickness along the lipid-water partition coefficient of the drug will affect the rate of diffusion NOTE: most drugs have molecular weights between 100-1500D and can therefore cross membranes by lipid diffusion (if they are lipid soluble)

pH>pKa

medium where the drug is dissolved has less protons present than the drug so the drug donates a proton [A-] predominates for weak acids and [B] for weak bases HA --> <-- H+ + A- BH+ --> <-- H+ B

pH<pKa

medium where the drug is dissolved has more protons present than the drug, so the drug gains a proton [HA] predominates for weak acids and [BH+] for weak bases HA --> <-- H+ + A- BH+ --> <-- H+ + B

The amount of water solubility is proportional to the difference between

pH and pKa Difference >2.0 --> >99% 2.0--> 99% 1.0-->90% 0.5--> 76% 0.0-->50% ** memorize this! Ex. Drug X is a weak acid with pKa of 5.4. What percentage of the drug was most likely water soluble in the patients plasma (pH of plasma=7.4) - look at difference between pH and pKa for drug; i.e. 7.4-5.4= 2 - above this difference of 2 corresponds to 99% (this means that the drug was most likely 99% water soluble in pts plasma. NOW in terms of lipid solubility: Ex. Drug X is a weak acid with a pKa of 5.4. What percentage of the drug was most likely lipid soluble in the pts plasma (pH of plasma is 7.4)? - To find our percentage that is lipid soluble it would be 100%-99%= 1% **Therefore, with Drug X, 99% is water soluble and 1% is lipid soluble

Most organs have dual innervation meaning that

parasympathetic and sympathetic nerve fibers - in most instances the two divisions of the ANS functionally/physiologically oppose each other * 2 divisions of the ANS work together to maintain homeostasis (nml physio) - most pathological conditions are result of dominance of one division of the ANS

Immunlogic components of vaccines are usually suspended in a liquid (usually sterile water or saline) that usually contains

preservatives, stabilizers and, in some cases, trace elements resulting from the manufacturing process

MOA of NSAIDs

primarily inhibit the cyclooxygenase enzymes that catalyze the first step in prostanoid biosynthesis --> this leads to decreased prostaglandin synthesis with both beneficial and unwanted effects Differences in safety and efficacy of the NSAIDs may be explained by relative selectivity for the COX-1 and COX-2 enzyme: - Inhibition of COX-2 is thought to lead to the anti-inflammatory and analgesic actions of NSAIDs

Differentiation

process of cell maturation: Progenitors --> Mature/differetiated cells capable to perform a specialized function, ex. secretion or contraction) - Differentiation in Oncology: resemblance of neoplastic cells and tissues to their nml mature prototypes, both morphologically and functionally

Inhibition of cyclooxygenase by NSAIDs diminishes the formation of

prostaglandins and, thus, modulates aspects of inflammation mediated by prostaglandins - NSAIDs inhibit early phases of inflammatory reaction (ex. vascular permeability, edema) by inhibiting PG and TX biosynthesis - NSAIDs have no direct effects on specific immunological responses Ex: NSAIDs inhibit inflammation in arthritis, but they neither arrest the progression of the disease nor induce remission **ANTI-inflammatory actions of NSAIDS

Incidence

rate, or occurence, or frequency of a disease - concerned with measuring the frequency of NEW cases - time period is important (mouth, year, etc.) Incidence= Number of NEW cases/ Number "at risk" to be a new case -------- Prevalence: TOTAL proprtion of individuals in a defined population that has the disease (or outcome of interest) at a defined instant in time - includes BOTH new and old cases (ALL cases) Prevalence= Total number of cases (new and old)/ Total # of ppl in a population (at a point in time) ----- Can decrease incidence and prevalence if focusing on prevention (decrease cases coming in) i..e a vaccine --- Cure for HIV that affects ppl who have it: decrease prevalence, no affect on incidence

When the cell membrane is depolarized voltage-gated Na+ channels cannot reset- this is called the

refractory period-- the Na+ channel cannoth generate additional action potentials Any nicotinic receptor agonist, including ACh is capable of producing depolarizing blockade in high concentrations ---- if you keep the cell activated the cell with NOT reset--> no more action potential (this is the depolarizing blockade) ** ACh can turn on nicotinic receptors but at high concentrations can eventually block them

Primitive Defenses

require distortion of reality (splitting, projection - significant social cost - associated with poor adaptation (acting out) Splitting: compartmentalizing contradictory aspects of selfs and others - i.e. "you are the greatest doctor unlike that unfeeling loser who wouldnt give me pain meds" Projection: disvowing unpleasant feelings and attributing them to others - primitive ways to handle dysregulation and unwelcoming impulses and thoughts - projection: perceiving and reacting to feelinds as if they are outside of you - projective identification: pressuring the other person to feel your feelings - i.e. "you're judging me arent you? i dont know how you could hate one of your pts" Acting out: impulsive, unconscious action replaces painful awareness -i.e. teenager with parents that are constantly fighting gets arrested for shop lifting

PGE2 is thought to

sensitize nerve endings to the action of bradykinin, histamine, and other chemical mediators released locally by the inflammatory process - By decreasing PGE2 synthesis, the sensation of pain can be decreased (ANALGESIC ACTIONS OF NSAIDs) - May also inhibit central actions of PGs, which facilitate pain transmission in the dorsal horn of the spinal cord - COX-2 is expressed during times of inflammation and injury, the inhibition of this enzyme is responsible for the analgesic activity of NSAIDs - NSAIDs are used mainly for the management of mild to moderate pain arising from musculoskeletal disorders

Adjuvants

substance that enhances the immunogenicity of antigens - Used in vaccines comprised of purified antigens (i.e. proteins) bc the proteins are not immunogenic on their own (i.e. tetanus toxoid req. adjuvant, pertussis toxin works as an adjuvant in DPT) - Stimulate APCs so they present Ag and express cytokines and co-stimulatory molcules to stimulate Ag-specific T cells Which childhood vaccines contain adjuvants? Those that do: - HepA and HepB - Diphtheria-tetanus-pertussis (DTaP, TDaP - Haemophilus influenzae type b (Hib) ) - Human papillomavirus (HPV) - Pneumococcal Those that DONT: - Live attenuated viral vaccines for: measles, mumps, rubella (MMR), chickenpox and rotavirus - Inactivated vaccines for: poli (inactivated polio vaccine or IPV)

Unless a drug is given IV or is absorbed cutaneously, it must be absorbed into the

systemic circulation to exert its effect - Absorption- process by which the unchanges drug proceeds from the site of administration into the systemic circulation Bioavailability (F) provides a quantitative measure of absorption- it is the fraction of a give drug dose that reaches the systemic circulation Ex: If Drug A is available as 2 diff products containing same dose of the drug, but the two products do not yield similar concentrations of the drug in the blood (when given to the same subject)- this means that the two products differ in their bioavailability - Drug A can be administered orally and intravenously ***NOTE: bioavailability of a drug is CONSTANT- and does NOT depend on the administered dose Ex. if bioavailability of Drug A when given orally is 40%, this will remain 40% if you administer 100mg or a 200mg dose of the drug - Similarly the bioavailability of the iV form of Drug A will be 100% regardless of the dose given IV

Comparing Means

t-test! Used in hypothesis testing to determine the statistical difference between two group means 1. Independent t-Test: used for 2 independent/different groups (control and treatment group) 2. Paired t-Test: used for one group (pre-and post-test) Independet variable: nominal (2 groups) Dependent variable: interval or ratio *** Independent variables are limited to 2 levels (i.e. categories) ------ Independent t-Test ex: compare BP by residency type - BP: interval/ratio (continuous) - residency type: fullt-time, part-time): nominal with 2 groups Paired t-Test: - breast cancer knowledge before and after education

Drugs need to bind to _____ to produce its effects

target D+R --><-- DR (drug binds because has affinity to receptor)--> Response Drug targets may include: - Physiological receptors: ligand-gated ion channels (i.e. Nicotine- agonist at ligand gated ion channel) , G-protein coupled receptors (i.e. Morphine a mu opiod agonist- a GPCR), steroid receptors (intracellular), tyrosine kinase receptors - Voltage-gated ion channels (i.e. Carbamazepine works to inhibit Na+ channels) - Transport proteins (i.e. fluxoetine inhibits serotonin transport) - Enzymes (i.e. Donepezil inhibits acetylcholine enzyme that breaks down acetylcholine) - DNA

Selective toxicity is attributed to

the biochemical differences that exist between microorganisms and human beings Ex: - Some bacteria have specialized and structured cell walls, whereas mammalian cells have simple cell membranes- Thus, drugs that interfere with the synthesis or integrity of bacterial cell walls (ex. penicillin) are toxic to bacteria, but harmless to the host - Bacterial ribosome (70S) is different from the eukaryotic ribosome (80S) and therefore the bacterial ribosome provides a good selective target for antibacterial drugs - Bacterial enzymes that catalyze the synthesis and replication of nucleic acids are diff. from those of eukaryotic cells and therefore they provide a good selective target for antibacterial drugs **Selective toxicity of antibiotics is relative - Antimicrobials are not totally devoid of toxic effects-- At higher doses, or in pts with some concomitant diseases (ex. renal or hepatic dysfunction) they can cause adverse effects

Half-life (t 1/2)

the time it takes for the serum concentration of a drug to decrease by half - it detemines the time to steady state during the continuous dosing of a drug (it also determines the dosing interval) - Steady state= the point at which the amt of drug administered over a dosing interval equals the amt being eliminated over the same period - It takes about 3-5 t 1/2 to reach steady state (for a drug administered on a continuous basis)- for first order reactions ** Allows for prediction of how much of drug will remain in body after administered Ex; after 1 half-life--> 50% of drug remains 2--> 25% 3--> 12.5% 3--> 6.25% 5--> 3.125% NOTE: If a drug is given continuously, it should be noted that the time to reach steady state plasms concentration is independent of the dose or the dosing interval and is dependent on the half-life - 50% steady state is reach after 1 half-life - 75% after 2 - 87.5% after 3 - 93.75% after 4 - 96.9% after 5 - 98.45% after 6 ** Generally by 5 half-lives- apprx 95% of steady state is achieved and for clinical purposes dosing adjustments for drugs are made at this time

Spare receptors are a property of full agonists. If the EC50 value is less than the KD value,

then the drug is able to produce 50% maximal effect withou binding 50% of available receptors. There is a surplus of receptors in the system, i.e. there are spare receptors

T or F: There is tremendous diversity in the nutritional requirements of bacteria. This is an important feature that is used for distinguising microbial pathogens

true

Repeated measures Design

used with dependent data A design that is characterized by multiple measures of the same variabla, typically on same sample Independent variables: nominal dependent varaiabls: 3 or more interval or ratio variables (i.e. time points) ex: study participants are measured at baseline and 3 months later

Genetic information can be transmitted by

vertical or horizontal transmission Vertical: Bacteria I pathogen with gene X---(binary fission)---> makes two different bacteria giving them gene X **Horizontal transmission: A bacteria with gene X gives gene X to a bacteria that is lacking gene X via a gene transfer event

Increased Diastolic BP is only affected by the

vessels (DIRECT) - alpha1 and beta2 receptors

Agglutination is

whole cells or aggregated antigens Agglutination reactions involved large antigenic molecules, such as whole cells - Ex: mixing RBCs with specific antibody would result in agglutination of the RBCs (this approach is used in routine blood typing and in the Coombs test procedure) - Cells carrying the A antigen are agglutinated by anti-A serum only while cells carrying the B antigen are agglutinated by anti-B serum only - Cells carrying both the A and B antigens are agglutinated by both anti-A and anti-B sera while cells carrying neither A antigen nor B antigen are not agglutinated

Describe the Eukaryotic Ribosome

(5SrRNA + 5.8SrRNA + 28SrRNA) + 49 polypeptides --> 60S subunit 18S rRNA + >33 polypeptides --> 40S subunit 60S + 40S --> Eukaryotic 80S Subunit

MAP=

(Blood Pressure) MAP=CO x TPR - CO affected by heart - TPR is affected by blood vessels NOTE: When solving problems where blood pressure is given. Start with the diastolic pressure first- its easier to determine the reason for the change bc the diastolic pressure is only affected by ONE variable: the diameter of the blood vessels CO= SV x HR A Decrease in BP leads to: 1. Increased symp activity--> can either increase activation of beta1 adrenoreceptor on heart--> increases cardic output--> increases BP and also increases activation of alpha1 adrenoreceptors on SM --> increased peripheral resistance --> increases BP ** Response mediated by symp. NS 2. Decreased renal blood flow which leads to decreased GFR and increased renin which give AngII which increases peripher resistance increasing BP and AngII also increases aldosterone which increases sodium, water retention and increases blood volume leading to increased cardiac output leadings to increase in BP ** Response mediated by renin-angiotensin-aldosterone system

CMV (cytomegalovirus) disease of the lung

(pneumonia and pneumonitis) is common in immunosuppressed pts and can be fatal if not treated - CMV often causes retinitis, colitis and esophagitis in pts who are severely immunodeficient (ex. pts with AIDS) - CMV is also responsible for failure of many kidney transplants- may be the result of virus replication in graft after reactivation in transplanted kidney or infection from the host

Full agonist, partial agonist, antagonist

** All have the same affinity for receptor but DONT produce the same effect Not all drugs that bind a target have the same effect - Efficacy - Intrinsic activity: ability of drug to activate target (ability of drug to bind leading to conformational change that will cause activity) Full agonist can reach 100% max effect - partial agonists have partial efficacy and partial intrinsic activity - antagonist have zero efficacy and zero intrinsic activity For receptors boound vs. Drug concentration - Bmax is the same for full agonist, partial agonist and antagonist- they can all bind to ALL available receptors- all have affinity for receptor but DONT have intrinsic activity to induce the response to that receptor

Protein synthesis inhibitors (antibacterial drugs)

- Animoglycosides - Macrolides and ketolides - Clindamycin - Tetracyclines and GLycylcyclines - Streptogramins - Others (Chloramphenicol, Linezoild, quinupristin- Dafoprisitin)

NSAIDS include

- Aspirin (acetylsalicylic acid), sodium salicylate, mesalamine - Piroxicam - Ibuprofen, naproxen - Indomethacin - Diclofenac, ketorolac - Celecoxib *** ALL NSAIDs listed are inhibitors of cyclooxygenases however, aspirin and celecoxib have notable differences from the others *** Another anti-inflamm drug includes: - Acetaminophen

Gram positive spore forming rods (bacilli)

- Bacillus anthracis - Clostridia (perfrigens, tetani, difficle)

beta3 receptor

- Bladder--> relaxes detrusor muscle - Fat cells --> activates lipolysis

A knowledge of normal microbiota and contaminant guides proper specimen handling and interpretation of results- Name some anatomic sites, that are normally "STERILE"

- Blood - Bone Marrow - Cerebrospinal fluid - Serous fluids - Tissues - Lower respiratory tract - Bladder ** Anything in these lab findings would indicate an infection

Gram negative rods (bacilli) related to animal sources

- Brucella (B. melitensis, B. abortus, B. suis) - Yersinia (Y. Pestis), Y. entercolicita) - Pasteurella multocida - Bartonella enselae

Obligate intracellular bacteria DO NOT Gram stain- describe them

- Cannot replicate outside of host cells - requires cell culture - usually no peptidoglycan (no beta-lactam target!) Includes: Chlamydia/Chlamydophila, Rickettsia, Orientia, Enrlichia, Anaplasma, Coxiella Chlamydia/Chlamydophila: - cannot make ATP - vacuolar growth (inclusion body) - protein cell wall - 2 forms Rickettsia - cytoplasmic or nuclear replication Orientia - cytoplasmic or nuclear replication Ehrlichia - Vacuolar replication (morula) - 2 forms Anaplasma - vacuolar replication (morula) - 2 forms) Coxiella - vacuolar replicaiton - 2 forms

9 Cs of Medical Law and Ethics

- Capacity and competence - Choice - Consent - Children - Confidentiality - Context of practice - Controlling risk and preventing harm - Conduct of others - Challenging topics: organ donation; genetic testng; HIV; abortion

How is immunohisto(cyto)chemistry used to diagnose cancers?

- Categorization of undifferentiated (anaplastic) malignant neoplasma - Categorization of leukemias and lymphomas - Determination of site of origin of metastatic tumors - Detection of molecules that have prognostic or therapeutic significance, ex: ERBB2/HER2- new and estrogen receptors

Signal Transmission at a Cholingergic Synapse

- Choline required for the synthesis of ACh is transported into the nerve terminal by the Na+ dependent transporter CHT - The enzymes ChAT catalyzes the synthesis of ACh from choline and acetyl CoA - ACh is transported into vesicles for storage by vesicular ACh transporter (VAChT) - The ACh vesicles fuse with the plasma membrane and ACh is released from the vesicles whena presynatpic action potential triggers the release from Ca2+ from the voltage-gated Ca2+ channel - ACh diffuses into the synaptic cleft and binds to postsynaptic and presynaptic receptors. ACh receptors are divided into 2 types nicotinic and muscarinic - Membrane bound acetylcholinesterase terminates the action of ACh by metabolism to choline and acetate

List some morphologic patterns of necrosis

- Coagulative necrosis - Liquefactive necrosis - Gangrenous necrosis - Caseous necrosis - Fat necrosis (enzymatic & traumatic fat necrosis) - Fibrinoid necrosis

Drugs bind to their targets to have an effect- they bind through

- Covalent interactions (rare) - Electrostatic bonds (more common- reversible) Drugs show: - Specificity (rare) drugs will bind to several targets, but will have high affinity for some targets and low affinity for other targets - Selectivity (common): generally choose conc. of drug that will have actions at the place we desire - Stereoselectivity: some drugs have optical isomers- (levodopa and dextrodopa- levodopa is recognized by AA decarboxylase enzyme so has greater biological activity - like L and R hand being similar but different)

What are some classes of cell cycle activators?

- Cyclins (D, E, A, and B subsequently according to appearnce in cell cycle) - Cyclin-dependent kinases (CDK4, CDK6, CDK2, and CDK1 subsequently) - Transcription factor E2F (family) Most important CDK inhibitors: - P16-- inhibits cyclin D-CDK4 - P21-- active along whole cell cycle Cell Cycle Activator Complexes: - Cyclin D/CDK4, Cyclin E/CDK2, CyclinD/CDK6 --> are active at G1/S, phosphorylate RB protein - Cyclin A/CDK1 and CyclinA/CDK2 active at S/G2 - Cyclin B/CDK1 active at G2M Cyclin D/CDK4 Complex and RB protein: Cyclin D phosphorylates CDK4--> CDK4 phosphorylates RB protein --> RB protein dissociates from the complex with transcription factor E2F--> E2F activation E2F activates genes essential for progression through S phase: - Cyclin E - DNA polymerases - Thymidine kinase - Dihydrofolate reductase ** If RB lost--> E2F will be free and here will be constant activation of cell cycle--> Retinoblastoma and many Visceral cancers Cyclin B/CDK1 Complex: Active at G2, G2/M, and M - Sensitive to radiation-induced double-strand DNA breaks Function: initiation of mitosis - breakdown of nuclear envelope - condensation of chromosomes, ec. Cooperates with ATM

What to do if a pt insists on leaving AMA

- DO NOT coerce, threaten, or try to scare pt into staying - Try to restore the alliance: listen to grievances, give legitatmate consideration, negotiate compromises (substance withdrawal sxs should be treated approriately, psychiatric consultation may be warranted) - If pt still wishes to leave, physician should calmly explain potential consequences, emphasizing benefits of further hospitalization Many hospitals have standardized procedures for documentation: - serves an administrative purpose but may be insufficient to protect against litigation - pts reasons for leaving and physicians concerns that have been communicated to pt should be clearly documented - Obligation (ethical and legal) to endure the pt is making an informed choice - If pt is incapable of understanding the need for continued treatment (ex. mental illness or severe medical illness) this should also be documented- involuntary treatment may be considered

How do defects in membrane permeability contribute to cell injury?

- Damage of mitochondrial membrane--> leakage of cytochrome c--> apoptosis - Damage of plasma membrane--> water-electrolyte imbalance - Damage of lysosomal membrane --> leakage of acid hydrolyses into the cytoplasm with their following activation in acidic environment (RNases, DNases, proteases, phosphates, etc.

What are some secondary changes that could occur in the bladder as complications of benign prostatic hypertrophy?

- Dilation and hypertrophy - Residual urine--> bacterial superinfection - Hydronephrosis--> chronic renal failure ** Hydronephrosis shows atrophic cortex and medulla, dilated calyx, and dilated pelvis and ureter Symptoms: - urinary urgency - frequency of urination - nocturia NOTE: the prostate gland is normally 4cm anything larger than this is considered enlarged

Phages play an important role in microbial pathogenesis- can you give some examples

- Diphtheria exotoxin of the bacterium Corynebacterium diphtheriae is produced only when that bacterium is infected with a specific prophage (beta phage) - Erythrogenic toxin causing sxs of scarlet fever is produced only when the group A streptococcus is infected with a specific prophage - Neurotoxin produced by Clostridium botulinum is encoded by a phage - Exfoliatin, an exotoxin that causes scalded skin syndrome, is produced by Staphylococcus aureus as a result of lysogenic conversion - A lysogenic phage encodes an exotoxin produced by Vibrio cholerae

Drug teratogenesis

- Drugs with MW less than 800-1000 can cross the placenta easily - Drugs at preg can have direct and indirect effects on fetus Direct: 1. toxic: ex- therapeutic dose of diazepam given to motehr a few hrs before delivery can cause muscle flaccidity, apnea attackes, sucking difficulty, etc. in the new borne= "Floppy baby" syndrome - toxic effects on fetus are generally reversible once drug is withdrawn 2. Teratogenic any agent able to cause an abnormal development of the feturs or the appearance of malformations (usually IRREVERSIBLE) To be a teratogen a drug must: - cause a characteristic set of malformation - exert its effect at a particular stage of fetal development - show a dose-dependent indidence Ex: severe chemical agents (ex. alcohol), ionizing radiations, intrauterine infections, RH incompatbility etc. - Durign stage of blastogenesis in which cells are still undifferntiated and totipotent (i.e. can form any one of the organisms differentiated cell type)- exposure to harmful agents may cause death of the embryo (all or none effect) - Stage of organogenesis: most sensitive to morphological teratogenic effects - high dose--> death, low dose--> malformations - functional damage is rarre since tissue maturation is only beginning - Stage of histogenesis: MOST sensitive to functional teratogenic effects - these effects may become evident only after many yrs (ex. alcohol) Indirect effect: 1. decrease in blood flow to placenta 2. Disease of mother

Why does culture matter as a physician?

- Improves communication, encourgaes trust, better adherence to treatment recommendations, greater pt satisfaction, better outcomes, preventing and addressing health inequities Health & Health Care Inequities: A measureable, systemic, avoidable, and unjust difference in health (or health care access, utilization, quality, and outcomes) between groups, stemming from diff in levels of social advantage and disadvantage Social Determinants of health: - education quality - employment/working conditions - neighborhood conditions - acess to transportation - discrimination based on race/ethnicity, gender, sexuality (ex. institutional racism) Ex: Racial Stress Data - Allostatic load (AL): physiological effects of chronic stress - Black ppl had higher AL - Differences unexplained by poverty, SES, etc - Black women had highest AL in comparison to male and white counterparts Joint Comminsion 2014: Cultural competency is important for pt centered care and communication (important to understand the characteristics of a group and ur pts individual experience in context)

What are the 3 mechanisms of error correction in prokaryotic replication?

- Initial - During synthesis by DNA pol III (proofreading) - After synthesis by DNA pol I (mismatch repair) *** 3 overall tries yields a LOW error rate (1 in 10^9- 10^12)

Direct Acting Selective beta-agonist drugs

- Isoproterenol - Dobutamine - Albuterol - Terbutaline - Mirabegron

Gram negative rods (bacilli) related to the respiratory tract

- Klebsiella pneumoniae - Haemophilus influenzae - Moraxella catarrhalis - Bordetella pertussis - Legionella pneumophila

Beta-Nonselective and alpha1-antagonists

- Labetalol - Carvedilol MOA: Competitive inhibition of Beta1, Beta2, and alpha1 receptors

using LEARN in interventions

- Listen with empathy and understanding to pts perception of the problem - Explain your understanding and perception of the problem - Acknowledge and discuss differences and similarities in the perception of the problem - Recommend treatment - Negotiate/Discuss an agreement on treatment and follow-up

What are some causes of RB protein inactivation?

- Loss-of-function mutation in RB gene, chr. 13 - Amplifications of CCND1 (cyclin D1) and CDK4 genes - Loss-of-function mutation in CDK inhibitors (p16/INK4A) - Binding and inhibition of RB protein by viral oncoproteins (E7 protein of HPV) - viral inactivation

Modifiable Health Risk Behaviors

- Low phys activity - Tobacco use - Poor nutrition - Excessive alcohol use - Sleep Apprx 1/2 of americans have a chronic health condition: - cardiovascular (heart disease, stroke) - cancer - arthritis - obesity: over 40% of americans are obese - diabetes (at current rate, 1/3 of americans will have diabetes by 2050) Motivational Interviewing Improve the following in Diabetic pts: - glycemic control - adherence to glucose monitoring - increased exercise - improved diet (particularly fruit/vegetable intake - use of food diaries - stress reduction

What are some clinically significant examples of metaplasia?

- Non-keratinizing --> keratinizing epithelium in the oral cavity, larynx, esophagus (leukoplakia aka keratinizing squamous metaplasia) - white in gums so thick that can not see blood vessels beneath - Non-keratinizing squamous--> intestinal epithelium in the esophagus (Barrett esophagus aka Intestinal Metaplasia) - red patches bc columnar epithelium is much thinner than non-keratinizing so can see blood vessels beneath - Columnar --> Keratinizing/Non-Keratinizing squamous epithelium in the bronchi and uterine cervix (aka Keratinizing Squamous Metaplasia in urinary bladder and Non-keratinizing squamous metaplasia in the bronchus) - Transitional --> Keratinizing/Non-keratinizing squamous epithelium in the urinary bladder - Gastric--> intestinal epithelium in the stomach - Skeletal muscles --> bone in myositis ossificans (muscle becomes inflammed- this is a benign condition- it never becomes malignant) - Myeloid metaplasia of liver and spleen

Describe the general structure of bacteria

- Some structures conserved - Others quite variable: may be used for differentiating strains or species (serotyping) - Some absent in some genera or species NOTE: Not all bacterial species have the same structures

Gram-positive genera include

- Staphylococcus, Streptococcus, Enterococcus - Listeria (seen in reproductive) - Bacillus, Clostridium - Actinomyces - Mycobacterium, Nocardia, Corynebacterium ** these are gram + by deffinition but have extra structures that we can use to identify further** * there are more gram-positive than this list!

Inhibitors of nucleic acid synthesis or function (antibacterial drugs)

- Sulfonamides and Trimenthoprim - Fluoroquinolones - Nitroimidazoles (metronidazole)

What are some conditions for growth of bacteria?

- Temperature - Oxygen (strict aerobes, microaerophiles, facultative/aerotolerant anaerobes/ strict anaerobes) - pH - growth factors, nutrients - increased CO2 (5%) - replication time (incubation time) - can give important clues Air: - 78% nitrogen - 21% Oxygen - 0.038% carbon dioxide - 1% Argon - Water is variable

Infection with a virus, sometimes depending on specific viruses and host cells, can lead to different outcomes:

- The infection can be productive (i.e. the infection process yields progeny virions) - The infection can be non-productive (i.e. no progeny virions are produced) Infection when considering viruses= delivery of viral nucleic acid (whether replicative cycle yields progeny virions or not is irrelevant - Non-productiv infections by viruses can lead to disease (ex. Human Pappillomavirus Infections or Human herpesvirus 4 or Epstein-Barr virus), just like productive viral infections may not necessarily lead to disease (ex. BK virus) Productive or non-productive infections can yield 2 outcomes: - Disease (in case of productive infections ex. Common cold, influenca, but non-productive infections can also lead to disease as in the case of some human papillomavirus types that cause carvical carcinoma- This carcinoma results from the transformation of squamous epithelial cells once the virus has lost its capacity to produce virions; the pathogenesis results from the virus' capacity to alter cell cycle reg. processes in absence of virus yield - No disease (most obvious case of non-productive infections, but some productive infections only cause disease in immunocompromised hosts- Ex. BK virus is ubiquitous and infection of nml individuals can lead to significant virus shedding in urine; however, infection, or re-activation of the infection in immunocompromised hosts leads to disease ex. hemorrhagic cystitis)

What are the effects of prostaglandins?

- Thromboxane A2 is critical to platelet aggregation-formation of clots - PGI2 inhibits gastric acid secretions (decreases gastric acid secretion) with PGE2 and PGF2alpha PROMOTE secretion of protective mucus at the stomach lining - PGI2 also functions as a vasodilator, venodilator, and inhibitor of platelet aggregation (inhibit platelet aggregation) - Some PGs are important for uterine contraction (may cause uterine contraction) - this may account for some cases of dysmenorrhea (painful period) - PGE2 and PGI2 cause VASODILATION in the renal arteries and are important for autoregulation of kidney blood flow **By inhibiting the production of prostaglandins, NSAIDs can therefore affect many of the processes listed above- we can therefore predict many of the NSAID side effects

Features of Tumor Circulation

- Tortuosity and leakiness of blood capillaries - Continuous growth of blood capillaries - Vasculogenic mimicry: blood flows through clefts formed by tumor cells; no endothelial lining - Blood vessel abnormalities--> infarctions, hemorrhages, and cysts

What are two types of movements used for drugs to be transfered across cell membranes?

- Transcellular movement: drug moves across cell membrane - Paracellular movement: drug movement through gaps or tiny junctions between cells Passage of drugs across membrnaes may occur by: - Passive diffusion - Carrier mediated transport (facilitated diffusion and active transport) - Endocytosis - Exocytosis - Bulk flow

What are the properties of capsules?

- Usually high molecular weight but composed of polymerized simple sugars: glucose, mannose, galactose - In rare cases can be protein or amino acids: ex. Bacillus anthracis capsule is composed of the polymer D-glutamate - Often expressed in vivo but not in vitro- may be phase variable Main functions of capsules: primarily protection* - prevent phagocytosis by PMN - adherence and colonization - prevent complement and Ab deposition - prevent desiccation

Describe the genetic mechanism of evolution of methicillin and vancomycin-resistant Staphylococcus aureus (MRSA and MVRSA)

- Vancomycin-resistant enteroccocus (VRE) contains plasmids with multiple antibiotic resistance and virulence factors - During co-infection, a MRSA may have acquired the enterococcal resistance plasmid (e-plasmid) by transformation (after lysis of the enterococcal cell and release of its DNA) or more likely, by conjugation - A transposon in the e-plasmid containing the vancomycin resistance gene jumped out and inserted into the multiple antibiotic resistance plasmid of the MRSA - The new plasmid is readily spread to other S. aureus bacteria by conjugation The resulting MVRSA is resistant to: - Beta-lactams - Vancomycin - Trimethoprim - Gentamycin/kanamycin/tobramycin quaternary ammonium disinfectants

Adverse effects and Contraindication of Choline esters (ACh, Carbachol, Bethanechol)- mostly predictable from the mechanism of action

- Visual difficulty on far vision or in dim light (pupils wont dilate) - Nause and vomiting (due both to increased GI activity and stimulation of muscarinic receptor in chemoreceptor trigger zone- CNS), abd pain, diarrhea - **Cough (drug-induced bronchospasm and increased bronchial secretion and potent cough stimuli) - Sweating, lacrimation, salivation - Flushing and warmth of the skin - Urinary urgency - Hypotension (direct acting on muscarinic)

Pathogenesis is Varicella-zoster virus (VZV)

- acquired by inhalation and primary infection begins in the tonsils & mucosa of the resp tract - virus then progresses via the bloodstream and lymphatic system to the cells of the reticuloendothelial system Secondary viremia then occurs and spreads the virus throughout the body and to the skin - virus infects T cells and these cells can home to the skin & transfer virus to skin epithelial cells - virus overcomes inhibition by IFN-alpha, and vesicles are produced in the skin Virus remains cell associated and is transmitted on cell-to-cell interaction, except for terminally diff. epithelial cells in lungs & keratinocytes of skin lesions, which can release infectious virus - Virus replication in the lung is a major source of contagion - The virus causes a dermal vesiculopustular rash that develops over time in successive crops- fever & systemic sxs occur with the rash *** VZV initially infects the resp tract--> spreds to the reticuloendothelial system and Tcells and then by cell-associated viremia to the skin NOTE: course in young children, is generally shorter and less severe than in adults ** Virus establishes latent infection of enurons, usually DRG and cranial nerve ganglia ** Herpes zoster results from depression of cell-mediated immunity On reactivation, the virus replicates and is released along the entire neural pathway to infect the skin, causing a vesicular rash along the entire dermation (herpes zoster, or shingles) --> damages the neuron and may result in very painful postherpetic neuralgia

Important tools for identification of bacteria grown in culture include:

- conditions for growth - colony morphology - cell morphology and arrangement - staining properties - biochemical properties Bacteria have biochemical properties that can be used to determine their identity: - some make enzymes that can be detected - some use particular biochemical process that can be observed Tests are usually performed on isolated bacteria, not on specimens - while test might be quick, may not be performed until day 2 or 3 after you send the specimen

Why are hospitals ideal environments for transmission?

- crowding of sources (i.e. sick ppl); and only the sickest are admitted - pts are immunocompromised- presenting conditions, treatments - invasive procedures- breach protective barriers - limited resources for cleaning, surveillance, pt follow-up, etc. Common nosocomial infections include: (85% fall into 5 categories): - UTI - Surgical site infections (SSI) - Pneumonia - Bloodstream infections (BSI) - GI -- i.e. Clostridium difficile-associated diarrhea (CDAD) Also from interventions that breach barriers: - catheter-associated UTI (CAUTI) - surgeries - ventilator-associated pneumonia (VAP) - central-line associated BSI (CLABSI) 70% are antibiotic resistant

Confrontation Skill Function

- identify incongruity or mixed messages in behavior, though feelings or meanings - increase pt talk and explain and/or resolve conflict - identify pt change processes in the interview and throughout treatment - mediate conflict resolution - resor(y)ation of the "heal-thy" NOTE: Many pts may need and even prefer a more direct challenge - Firm confrontation may be necessary for a pt who is acting-out or antisocial - they may sneer at and manipulate "nice" helpers but be more likely to respect and work with a phys who listens and offers respect but take no "deception" from pt ** Empathic listening remains central if you are going to establish any type of working relationship

Effective Communication in Clinical Setting increases the likelihood that

- info gatheres from pts used to make diagnostic assessments is accurate and reliable - pts recognize that the physician is genuinely interested in them and their care - physicians and pts reach common ground on diagnosis and treatment - pts are motivated to play an active role in their own care Better communication leads to better outcomes: - reasearch shows communication is positively related to specific illness outcomes - satisfaction among pts and phys. Poor communication has been related to: - medical errors - malpractice suits - pt decisions to leave practices or health care organizations NOTE: Knowledge & skills associated with effective communication and intervewing can be improved through practice "Science" of communication vs. "art of communication- natural talent which one has from birth"

For antibacterial (antibiotics), mechanisms or targets include:

- inhibit cell wall synthesis in bacteria and fungi - cell membrane synthesis - synthesis of 30S and 50S ribosomal subunits - nucleic acid metabolism - function of topoisomerases - inhibit gene expression in bacteria in a sequence-specific manner

Describe Initiation of Translation in prokaryotes

- small ribosomal subunit sep from large with help of initiation factors: IF1 and IF3 - this complex then binds purine rich region (shine delgadro)- upstream of AUG on mRNA - shine delgardo seq is BP to compl seq on 16s RNA (component of small subunit)- ensures start codon is in right position wihtin ribosome - IF2 brings initiator tRNA charged with N-formyl-methionine - large ribosomal factor joins complex and IF are release Sites: - A= entry for new tRNA charged with amino-acid or amino-acyl tRNA - P= peptidyl-tRNA carries growing polypeptide - E= exit for tRNA after done delivering AA initiator tRNA positioned in p- site ** Initiation also uses GTP Elongation: - new tRNA carrying AA enters A site of ribosome - in ribosome- anticodon of incoming tRNA matched to mRNA codon in the A site - tRNA with wrong anticodon rejected and replaced with new tRNA (proofreading) - right tRNA in A site makes peptide bond between two adjacent AA - peptide bond forms- tRNA in P site releases AA to A site and becomes empty - ribosome moves 1 triplet forward on mRNA - empty tRNA on E site and peptidyl tRNA is in P site and A site is ready for new tRNA - cycle repeated for each codon on mRNA Termination: - When one of 3 stop codons positione in A site- no tRNA match this seq so cant fit in A site - recognized by release factors- cleaves bond between polypeptide and tRNA - polypeptide release and ribosome disassociated into subunits

Peptidoglycan (PG) (aka Murein aka Cell Wall) differs between different types and species of bacteria in terms of

- thickness - shape - chemical structure Ex: Gram negative bacteria have a THIN PG layer and gram positive have a THICK PG ** PG is the basis for gram stain Structure of PG: Made up alternating GlcNAc (NAG) and MurNAc (NAM) - Peptide tail on NAM covalently linked to tails of other strands (tetrapeptid- tetrapod tail) NOTE: humans have L- form AA, D form of AA in tetrapod tail is NOT found in humans so it makes for a good target - Alternating NAG and NAM makes a 3D multilayered net- Porous (provides strength) - Peptide part can vary a bit, MurNAc can be "decorated", but in general highly conserved

How does cytomegalovirus (CMV) evade innate and immune responses?

- virus prevents antigen presentation to both CD8 cytotoxic T cells and CD4 T cells by preventing the expression of MHC I molecules on the cell surface and by interfering with cytokine-induced expression of MHC II molecules on antigen-presenting cells (including the infected cells) A viral protein also blocks NK-cell attack of CMV-infected cells--> similar to EBV, CMV also encodes an IL-10 analog that would inhibit TH1 protective immune reponses ** CMV has been implicated as a cofactor for medulloblastoma (most common malignant brain tumor in children) , leukemia, and other diseases - CMV induced inflammation and promoted production of interleukin 6, vascular endothelial growth factor, and prostaglanding E2, which promoted the growth of medulloblastoma cells * treatment with ganciclovir and a non-steroid anti-inflamm drug stopped the growth of these cells

Physiological barriers to drug distribution

1. Blood brain barrier - Drugs may cross BBB to reach CNS across the cerebral capillaries (plasma to extracellular fluid) or across the choroid plexus (from plasma to CSF) - Limitation due to: tight jxs between endothelial cells, unavailability of transport vesicles, and lack of transcellular pathways especially for hydrophilic drugs * Several drugs are actively transported out of the CSF and back into the blood by a P-glycoprotein, present in epithelial cells of the choroid plexus Drugs that CAN favorably cross BBB: - high lipophilicity, small size and MW, unionized at physiologic pH - transfer of drugs across BBB mainly by lipid diffusion * Drugs that DONT cross BBB are administered by intrathecal injection directly into CSF (if action on CNS is required) 2. Placenta - Barrier between maternal and fetal blood vessels (most drugs taken by mother reach the fetus- the placental barrier is generally quite permeable to drugs) Factors affecting placental transfer of drugs: 1. Molecular size of drugs (drugs with MW > than 1500 cross the placenta poorly) 2. Physiochemical properties (lipophilic, unionized drugs BOTH cross placenta readily*) 3. Degree of protein binding 4. Placental blood flow 5. Stage of placental development (passage seems easier during 3rd trimester) 6. Placental drug metabolism (placenta is site of metabolism of some drugs ex. ethanol) 7. Activity of P-glycoprotein that is present in placental vessels which can put some compounds back into maternal blood

Developmental accomplishments between 0-18 yrs

1. Cognitive/intellectual deve. (including lang. develop) - emergence of ability to think and understands Jean piaget (4 stages) - sensory motor (0-2yr) - pre-operation (3-6) - concrete operational (7-11) - formal operation (12-18) Neo-piagetian theories (info processing mechanisms); - lang - attention control - working memory Review: - Newborn and infant: object permanence - Toddler: numbers, opposites, time, space and direction, body parts - Pre-school: past and present, questions, group and match, counting; alphabet, attention (5-15 min) - School age-12yo: logical and concrete thinking, conservation (lack of conservation nml in preschool) - Adolescence: abstrat reasoning 2. Social deve. - Newborn and infant: attachment/binding - Toddler: express emotion, parallel play, "temper tantrums" - pre-school: lets pretend games; imaginary friends - school age- pre-puberty: empathy, loyalty, socialization, forging freindships - adolescence: independence, peer pressure, challenging rules, transition to adult personality 3. Sexual deve. - toddler: gender identity: male vs. female - pre-school: sexual curiosity- with no interest in sexual gratification - school age (pre-pubert): latency period- no interest in opp gender, gender identification - adolescence: sexual exploration with interest in sexual gratification

Vd does NOT have a true anatomic space and is therefore referred to as the apparent Vd- what are factors affecting Vd, describe them

1. Drug MW - low MW drugs can diffuse across biological membranes and distribute to the tissues better than high MW drugs 2. Lipid Solubiliy - Lipophilic drugs distribute FASTER to tissues than hydrophilic drugs - Hydrophilic drugs have a LOW Vd are are distributed predominately into the extracellular fluid (ECF) 3. Ionization in physiological pH ** see PK1 lecture- ionized drugs become trapped depending on the pH of the medium - this fact can be used to make the drug concentrate in specific compartments 4. Protein Binding - Drug in the systemic circulation can bind to plasma proteins such as albumin, alpha-1-acid glycoprotein and lipoprotein - Albumin (3-4.5g/L)- Binds anionic and cationic drugs (Ex. Phenytoin) - Alpha-1-acid glycoprotein (0.4-1)- Binds cationic drugs (Ex. Lidocaine) - Lipoprotein (Variable conc.)- Binds lipophilic drugs (Ex. Cyclosporin) - Binding of drugs to plasma proteins is REVERSIBLE but only free drugs can diffuse into tissues and exert a pharmacological effect - The ratio of bound drug to free drug is CONSTANT, when the drug plasma concentration falls (due to metabolism or elimination)- bound drug proportionally dissociates from albumin (Ex. if protein binding= 70%, if plasma concentration decreases it will unbind to maintain this ratio) ** A constant percentage of the drug is bound, therefore protein binding is independent of the dose - Accumulation of ENDOGENOUS compounds that can compete with drugs for their binding sites results in reduction of the percent drug bound and increase in the drug free fraction- this occurs hyperbilirubinemia, jaundice, renal failure, and liver disease - EXOGENOUS compounds such as drugs with high protein binding affinity (ex. warfarin, valproic acid, and NSAIDs) can compete and displace other drugs from their protein binding sites 5. Blood flow - Changes in blood flow can influence drug uptake by tissues. Distribution is therefore dependent on blood flow and the rate of delivery of drug via the blood stream to the tissues 6. Disease states - In heart failure, CO is reduced, and this is associated with a reduced volume of distribution of some drugs; in hepatic disease there may be a reduction in the production of albumin which will affect protein binding; etc.

3 typical uses of Antimicrobial drugs?

1. Empiric therapy Antimicrobial treatment done WITHOUT the lab identification of the specific pathogen. It is used when: - history of the pt and the site of infection can reliably suggest the offending pathogen - severity of the disease requires immediate treatment- in this case therapy is initiate before results of cultures are available 2. Specific therapy Specific antimicrobial treatment done after identifying the causative pathogen by: - Prelimary tests (ie. Gram-stain) can lead to targeted treatment - Cultures, susceptibilty testing can lead to definitve treatment 3. Prophylactic therapy Done to prevent rather than to treat an infection - Indiscriminate use of prophylatic antimicrobial therapy can result in bacterial resistance and superinfections - Therefore prophylatic therapy is RESTRICTED in certain clinical situations where benefits outwiegh the potential risks (ex. In some HIV+ pts, Azitrhromycin is given when CD4 cell count is below 50cells/mm^3

Steps in the infectious cycle of most pathogens

1. Entry/Attachment: enter the host, move to a surface, attach to a surface 2. Local or general spread: evade immediate local defenses 3. Replication/Colonization: increase bacterial numbers 4. Evasion of host defenses: evade immune and other defenses long enough for the full cycle in the host to be completed 5. Damage (pathology/disease): not strictly necessary but often occurs 6. Shedding from body (transmission): leave body at a site and on a scale that ensures spread to fresh hosts

What are the 4 core principles of motivational interviewing?

1. Express empathy- lecturing/shame does NOT work - Accept the person, their situation, their point of view - Respect their explanations - Reflective, skillful, nonjudgmental listening - Avoiding criticisim and blaming - Support self-esteem - Ambivalence is normal - Demonstrate an understanding of pts perspective (reflection of affect/emotion) - Labelling is unnecessary 2. Develop discrepancy- between current and desired behavior - Clarify important goals - ask for help in understanding - be sincerely curious - use "so", "if" reflectively - let pt make the argument for change - explore consequence or potential consequences of pts behavior - create and amplify the discrepancy between behavior and goals ** Ambivalence: state of having simultaneous, sometimes conflicting feelings towards something-like feeling happy and sad at same time 3. Roll with resistance- everyone is ambivalent - argument breeds defensiveness - if it arises, stop and find another way to proceed - avoid confrontation - go with the direction of the pts argument - suggest new perspective, but dont insist on them - "take what you want, leave the rest" 4. Support self-efficacy- individual autonomy - belief in the ability to chnage (self-efficacy) is an important motivator - explore strengths and highlight positive exceptions - emphasize small steps- realistic hope - maintain confidence and optimisim - anticipate a diff future - pt is responsible for choosing and carrying out personal change

Which types of molecules are more easily excreted in the urine?

1. Free drug enters glomerular filtrate 2. Active secretion of drugs 3. Passive reabsorption of lipid-soluble, un-ionized drug, which has been concentrated so that the intra-luminal concentration is greater than that in the perivascular space *** In step 3: there is passive reabsorption of lipid soluble unionized drug molecules - In case of managing salicylate toxicity: alkalinizing the urine will lead to more IONIZED lipid INSOLUBLE molecules which will be easily excreted (pH>pKa)

What are the basics of viral classification?

1. Genome: - Composition: DNA or RNA - Strandedness: single, double, partially double - Arrangement: linear, circular, segmented, diploid 2. Capsid (nucleocapsid) symmetry - Helical (helicoidal, filamentous) - Icosahedral (spherical) 3. Envelope - Presence (enveloped) - Absence (non-enveloped, naked) (enveloped vs. naked) 4. Shape - Regular, spherical, icosahedral, helical, ovoid - Complex Viruses have varying complexity (i.e. can be a complex retrovirus like HIV or simple virus)

Describe growth activation in a Nml cell

1. Growth factor binds receptor 2. Transmission of a signal across the cytomembrane 3. Activation of signal-transducing proteins 4. Transmission of a signal across the cytosol to the nucleus via secondary messengers 5. Activation of nuclear regulatory factors that initiate DNA transcription 6. Entry and progression of the cell through the cell cycle (MAPKinase pathway) Ras--> Raf--> MAPK--> transcription factors

Choosing an appropriate statistical test

1. Hypothesis: distinguish dependent and independent variable 2. Answer following questions to decide which statistical test is appropraite to analyze your data: What is the variable type for the dependent variable? - interval/ratio vs. nominal/categorical; skewness? time? - if more than one outcome, are they paried or related? What is the variable type for the independent variable? - interval/ratio vs. nominal/categorical (1 group, 2 groups, >2 groups) - for 2 or >2 groups: independent (unrelated)/ paired (related) 3. any other covariates, confounding factors?

What are some pt factors that can affect the therapy outcome of Antimicrobial drugs?

1. Impaired immune system Immunity is compromised in pts with - advanced age, diabetes mellitus, alcholism, malnutrition, HIV infection - immunosuppressive therapy - cancer chemotherapy ** Since intact host immunity is req. to eliminate the infecting organism, bactericidal antibiotics are preferred in pts with impaired immunity 2. Renal dysfunction - Poor renal fx. can lead to accumulation of antibiotics that are mainly eliminated by this route- Serum creatinine levels are used as an index of renal fx. for adjustment of dosage of these antibiotics --> Notable: Aminoglycosides 3. Hepatic dysfunction - Antibiotics eliminated mainly by liver are NOT indicated in the case of severe liver dysfx. 4. Site of infection - Antibiotic access into abscesss is poor due to poor perfusion. Therefore, in many cases the abscess must be surfically drained for the proper cation of antibiotics - Some tissues (prostate, vitreous body of the eye, testes and CNS) have natural barriers to drug delivery 5. Age - Renal and hepatic functions are poorly developed in the new born and are diminished in the elderly- therefore some antibiotics are contraindicated or a proper dose is needed in these ages 6. Pregnancy Most anitmicrobials cross the placent and can affect the fetus *Antibiotics that should be avoided during pregnancy include**: - Tetracyline and glycylcyclines - Aminoglycosides - Fluoroquinolones - Sulfonamides - Some macrolides (erythromycin estolate, clarithromycin)

Metastatic Cascade

1. Invasion of basement membrane - Loss of E-cadherin and/or Beta-catenin - Synthesis of matrix metalloproteinases (MMPs, classes 1-28--> ECM degradation, particularly type IV collagen) - Spread of integrins and other adhesion molecules "all over the cell surface" 2. Movement through extracellular matrix 3. Vascular dissemination 4. Homing and colonisation (extravasation) - Site of extravasation is determined by natural pathways of drainage, ex. by lymph or blood stream Exemptions: - Cancer never metastasizes to the skeletal muscles - Metastases to the spleen and heart are extremely rare Mechanisms of Extravasation: - Principle: tumor cells and the endothelium in certain organs have corresponding adhesion molecules and their ligands Ex: cells of solid tumors express CD44

Bacterial Growth is tightly controlled- What are the four stages of their growth

1. Lag phase: - Nutrients are transported into the cell - Enzymes are being synthesized - Recovery from damage caused by heat, radiation or toxic chemicals - Need to prepare for cell division: increase in cell size, replication of DNA etc. 2. Exponential or Log Phase - All growing cells in the population are actively growing and dividing - During this phase there is a time of balanced growth, when there are proportional increases in all cell constituents over a period of time 3. Stationary Phase - If E.coli with a generation time of 20 minutes was to grow exponentially for 48hrs, there would be a 10^45 increase in bacterial numbers. This would represent about 10^25 tons of E.coli this is many hundreds of times the total mass of the planet - This obviously doesnt occur bc growth ceases as an essential nutrient runs out or toxis products accumulat (ex. acids to drive pH down) - Stationary phase doesnt mean that there is no growth or metabolism but that the number of growing and dying cells balance each other out 4. Death phase - The number of cells that are dying is greater than the number that is growing. The death phase may, but not always, involve cell lysis - Even though cells are not growing, bacteria can still cause damage- immune responses, toxins released, LPS

4 topics chart

1. Medical indications - what are the indications for and against treatment? - beneficence & nonmaleficence 2. Patient preferences" - what choices does the pt make about treatment decisions? - autonomy 3. Quality of life? - what degree of satisfaction dose pt experience and value? - beneficience, nonmaleficence and autonomy 4. Contextual factors? - how legal, institutional, familial, personality, financial, religious factors affect decisions - justice

What are the basic properties of bacterial attachment?

1. Nonspecific (docking) - reversible transient binding to surfaces - usually occurs first - forces involve hydrophobic and electrostatic interactions - typically low affinity interactions 2. Specific (anchoring) - reversible permanent binding to surfaces - usually occurs second - "lock and key" bonds between two complementary molecules on each cell surface - typically high affinity interactions

What are the 2 main groups of Helminths?

1. Platyhelminthes (Flat worms) - Tramatodes- flukes - Cestodes- tapeworms 2. Nemathelminthes (Round worms- Nematodes) - Intestinal worms - Tissue worms- filarial worms

What is Psychoanalysis?

1. Procedure - psychotherapy - method of study 2. Theory of Pesonality and Mind **Psychoanalysis Central tenet: Behavior (symptoms) largely influenced by unconscious forces Primary process (unconcious level) - immoral urges, selfish needs, shameful experiences Secondary process (conscious level): - thoughts and perceptions Evidence: - dreams - parapraxes - hypnosis - subliminali influence - implicit associations Freuds Evolution of thought: 1. Topographical model- the iceberg (assumption: make it conscious,have a cathrasis, get cured) 2. Structural model- the conflicted iceburg--> introduces conflict between drives - instinctual drives= sex & aggression - conflict with societal expectations Contemporary Psychoanalysis Theory: - modern structural theory--> Ego psychology - object relations theory--> child seeks relationships, not just drive fulfillment - self psychology--> child needs mirroring to develop sense of self/deficit model Practice: - Psychoanalytic Psychotherapy- off the couch - Therapist more active and accessible Key Areas of Convergence: - Continuum (health is on a continuum) - Early childhood development- repitition compulsion - Unconscious mental processes - Treatment- free association, analysis of transference - Theory and clinical data

List the mechnism and given exampls of resistance to Antimicrobial Drugs

1. Production of microbial enzymes that inactivate the drug Ex: - Beta-lactamase production** (resistance to beta-lactam anitbiotics) - Transferase production (resistance to aminoglycosides) - Esterase production (resistance to macrolides) 2. Development of microbial targets with decreased drug affinity Ex: - Decreased topoisomerase affinity (resistance to fluoroquinolone) - Decreased 50 ribosomal subunit affinity (reisstance to macrolides) - Decreased 30 ribosomal subunit affinity (resistance to tetracyclines) 3. Decreased drug concentration inside bacteria due to: a. Decreased permeability of cell membrane to the drug - Resistance of many gram neg. bacteria to penicillins - Resistance of fluoroquinolones, aminoglycosides and tetracyclines b. Development of an active multidrug efflux pump - Resistance to beta-lactam antibiotics, macrolides, fluoroquinolones, tetracylcines 4. Increased production of an essential metabolite Ex: a. Increase production of PABA (resistance to sulfonamides)

Parasites are either

1. Protozoa - unicellular organisms - the first "animals" 2. Metazoa (Helminthes) - Multicellular organisms (LARGE!) ** Know if a parasite is a protozoa or helminth (drug targets are different)

What are the basic types of fungi?

1. Yeasts are single celled fungi which replicate by budding. Monomorphic yeasts have only yeast forms (and buds) 2. Mold: a fungus that grows in the form of multicellular filaments called hyphae - monomorphic filamentous - hyphae form together to produce a matlike structure called a mycelium - many produce airborne spores (conidia) 3. Dimorphic fungal pathogens: fungi which convert from a filamentous form to a yeast or yeast-like form in the body (Yeast--> Mold --> Yeast) - Mushrooms, puffballs, morels, etc.: these are fruiting bodies of filamentous fungi with sporulating surfaces

2 types of antibodies that can be administered to confer passive immunity

1. immune globulin (non-specific standard immunoglobulin, or gamma globulin) - mix of plasma proteins and a broad spectrum of antibodies (predominantely of the IgG isotype) obtained from plasma donors - sine these immunoglobulins come from diff donors, they have a range of specificities to various antigens arising both from natural immunity and from immunization - this is administered for prevention or attnuation of disease for which there are no specific immunoglobulin preparations 2. hyperimmune human immunoglobulin preparations - contain high conc. of antibodies specific for a particular pathogen or toxin - they are administered to pts who have been exposed to specific pathogen, or a specific toxin (ex. after being stung by certain scorpions or bit by certain snales- anti-venoms etc.) **There are known adverse effects associated with injection of preformed antibodies- pts can mount a response against the antigenic determinants of injected (foreign) antibodies and can develop serum sickness or systemic anaphylaxis

Phenylephrine

A pure alpha1 agonist Route of Administration: Oral, IV, topical, opthalmic and nasal (route dictated by clinical use) MOA: selective alpha1 agonist Effects: - Vasoconstriction; peripheral vascular resistance is increased and BP is maintained or elevated. Associated with bradycardia due to activation of the baroreceptor reflex - Contraction of radial muscle (pupils will be dilated) - common use in eye exams bc there is no effect on lens Clincal use: - Nasal decongestant: temp relief of congestion due to colds and UR allergies - Hemorrhoids (BV shrinking) - Mydriasis: dilate the pupils (eye exam) - Hypotension/Shock: a. Hypotension during anesthesa: maintain BP during spinal and inhalational anesthesia b. Cardiogenic shock: due to aortic stenosis, mitral stenosis or dynamic left ventricular outflow tract obstruction. Use with extreme caution, increase systemic vascular resistance may significantly reduce CO due to an increase in cardiac afterload. Not firest choice drug - NOT recommended for routine use in septic shock- NE is the first choice of drug Adverse effects: - Rebound nasal congestion: frequent use may cause nasal congestion to recur or worsen - Blurred vision - Hypertensive crisis - Reflex bradycardia (can be severe) - Ischemia to vital organs - Worsening of heart failure or angina Contraindications: - Severe hypertension - Preexisting bradycardia, partial heart block or severe coronary artery disease - Pt with autonomic dysfunction- may show an exaggerated increase in BP - Hyperthyroidism- increased sensitivity to sympathomimetics

Decribe the replication of RNA viruses

ALL RNA viruses must encode their own RNA-dep RNA pol (w/ exception of retroviruses which encode a reverse transcriptase) bc cells do not posses such enzymes - Negative polarity ssRNA viruses MUST carry RNA-dep RNA pol when penetrating host cell; otherwise RNA rapidly gets degraded bc (-) ssRNA is unusable by ribosomes and, given that cells have no RNA-dep RNA pol, the RNA will linger until degraded which occurs rapidly - If virus penetrates cell carrying its polymerase (which is usually complexed with RNA- thats the best way to ensure that poly will follow the genome) , then (-)ssRNA soon gets amplified via a (+) ssRNA intermediate Once capsid proteins have been synthesized from (+)ssRNA translation, the (-)ssRNA will be packaged into newly synthesized capsids to form progeny viral particles Positive-polarity ssRNA viruses on other hand.. - immediatly initaite protein syn by connecting to ribosomes after penetration - viral particle doesnt need its own polymerase bc the (+)ssRNA acts as mRNA and the RNA-dep RNA pol can be translated directly from that RNA species (possible bc RNA of these viruses is capped and polyadenylated, ot the viral equivalent thereof, such as IRES (internal ribosome entry site) which acts as 5' cap-dependent manner in association with cellular endosomal/microtubular system - once pol has been syn, then RNA amplification can start - amplifies (+) ssRNA will serve both as mRNA and genomic RNA to be packaged into progeny particles dsRNA viruses follow the (-)ssRNA replication strategy, bc ribosomes only recognize ssRNA and dsRNA req. enzymatic activity (under natural conditions) for denaturation

Pharmacologic effects of Beta-Antagonists

ALL beta-blocker effects are pronounced when sympathetic tone is high, but may be small when the tone is low Cardiovascular effects: Heart: - frequency, conduction, automaticity and contractility of ther heart are decreased (less with compounds that are partial agonists) - lowered freq. and contractility decrease CO - myocardial perfusion in certain parts of the heart is increased- may be due to increased filling time - cardiac O2 demand is lowered more than O2 supply (more efficient) Vessels: - All beta-blockers produce peripheral vasodilation- several properties have been proposed to explain this effect and they vary with diff. drugs- However the one common to all beta-blockers is the blockage of beta1 receptor mediated renin secretion - Blood pressure is NOT decreased in healthy individuals but IS decreased in hypertensive pts; the mechanism is not fully understood but most likely involved decreased CO and decreased renin secretion Ocular effects: - Decreased production of aqueous humor by ciliary epithelium Metabolic and endocrine effects: - Decreased release of renin - Inhibition of sympathetic-mediated lipolysis and liver glycogenolysis and gluconeogenesis (minimal with selective drugs) - Blockade of adrenergic activation due to hypoglycemia - Blockade of catecholamine-induced tremor - Decreased K+ uptake by skeletal muscle (with nonselective drugs) Respiratory effects (this is a negative NOT therapeutic effect): - Bronchoconstriction is minimal in normal individual bu tcan be life-threatening in pts with asthma and COPD - Bronchoconstriction is less pronounced (but not completely avoided) with selective (beta1) compounds Local anesthetic effects: - Drugs with this action are NOT used topically on the eye (NOT used for Gluacoma)

MOA of Choline Esters (ACh, Carbachol, and Bethanechol)

ALL choline esters and natural alkaloids activated M1, M2, and M3 receptors - activation of postsynaptic receptors alters the function of effecotr organs - activation of presynaptic receptors inhibits the release of various NTs Some choline esters activate nicotinic receptors - Initial activation on nicotinic receptors causes depolarization of postjunctional cell membrane which triggers the AP and therefore the response of the effector organ - Prolonged activation of nicotinic receptors causes persistent depolarization of postjunctional cell membrane that prevents the return to the resting state. Since it is the change in resting potential that triggers the AP, the depolarized membrane is resistant to further depolarization and the response of the effector organ is blocked

Disclosing Medical Errors

AMA Code of ethics REQUIRES phys to disclose medical errrors to pts ** Reasearch shows oppenness, transparency, and full disclosure promotes healing of all involved and reduces cost of litigation - Increadingly US med schools and facilities are adopting a communication and optimal resolution process Full Disclosure - Explanation: timely accounting of what went wrong and why (maintains pt trust, improve safety knowledge) - Responsibility: appropriate ownership by providers and/or facility for what went wrong (reduce likelihood of lawsuit) - Apology: sincere apology with expression of providers distress and sympathy for pt and/or fam (experience emotional relief, lessen likelihood of second victom phenomenon) - Prevention: promise effort will be made to learn from event and prevent similar recurrence (strengthen and reinforce a culture of safety) - Compensation: non-adversarial process to ensure financial reparations (hasten resolution and healing, decrease litigation and settlement time and costs)

Fatty change

Abnormal accumulation of triglycerides in the cytoplasm of parenchymal cells Organs affected: - Liver (most common) - Heart, muscles, and kidneys Causes: - Alcohol abuse (most common) - Protein malnutrition (kwashiorkor) - Other: Reye Syndrome, anemia, infectious diseases Microscopic changes: - Non-stained (clear) "punched out" vacuoles within the cytoplasm, if stained with H+E (single or multiple) - R/o water and glycogen accumulation (oil red--> lipids will be red, Sudan IV (sudan black)--> lipids will be black

Pathologic Calcification

Abnormal deposition of calcium salts in tissues Gross appearance: fine white granules with gritty texture Histology: - intracellular and/or extracellular deposits of amorphous basophilis material - Large round laminated inclusions: PSAMMOMA BODIES (greek "sammos"-sand) ***2 Types of Calcifcations: Dystrophic and Metastatic Dystrophic Calcification - of previously damaged or necrotic tissues - *normal serum level of calcium Causes: - caseous necrosis in TB - enzymatic fat necrosis in acute pancreatitis - traumatic fat necrosis of the breast - damaged heart valves: mitral and aortic stenosis - artherosclerotic plaque - neoplastic and preneoplastic conditions (i.e. ductal carcinoma in situ of the breast, oligodendroglioma, and Thyroid and ovarian carcinoma, and meningioma) Ex: Aortic Valve and Atherosclerotic plaque Metastatic Calcification - *of NORMAL tissues due to HYPERCALCEMIA Causes of hypercalcemia: - increased serum level of parathyroid hormone (primary hyperparathyroidism: parathyroid tumors, etc.) - bone destruction: multiple fractures, bone and bone marrow tumors, immobilization, etc. - vitamin D-related disorders, ex. sarcoidosis - Renal failure: retention of phosphate with following secondary hyperparathyroidism Multiple organs can be affected simultaneously: - gastric mucosa - kidneys - lungs - systemic arteries and pulmonary veins Common feature: increased pH--> instability of calcium solutes

Dysplasia

Abnormal growth or development (as of tissues or cells) Criteria: loss in the uniformity of the individual cells and loss in their architectural orientation Location: - organs lined by stratified squamous epithelium: skin, oral mucosa, larynx, pharynx, esophagus, anus, vulva, and uterine cervix - organs lined by other epithelia: urinary bladder, stomach, bronchi etc. ** Dysplasia is REVERSIBLE process and MAY lead to malignant transformation Among all acquired predisposing conditions, ONLY dysplasia has a REAL RISK of cancer - Chronic inflammation, hyperplasia, metaplasia, and benign tumors form a background for dysplasia with a possibility of malignant transformation

Tissue Atypia

Abnormal tissue architecture ** Abnormal size and shape of tissue components - Abnormal glands in adenoma or adenocarcinoma - Abnormal muscle bundles in leiomyoma or leiomyosarcoma Changes in parenchyma/stroma ratio: - an increase in parenchymal volume - an increase in stromal volume: desmoplasia (scirrhous cancer) Loss of orientation (loss of polarity) - Ex. presence of immature cells wihtin the upper layers of stratified squamous epithelium **Tissue atypia is seen in BOTH benign and malignant neoplasms

Sublingual administration

Absorption pattern: - primarily by lipid diffusion - few drugs (ex. nitroglycerin) have rapid, direct systemic absorption - most drugs erratically or incompletely absorbed Advantages: - bypasses first pass effect - bypasses destruction by stomach acid - drug stability maintained bc the pH of saliva is relatively neutral - may cause immediate pharmacological effects Disadvantages: - limited to certain types of drugs - limited to drugs that can be taken in small doses - may lose part of the drug dose if swallowed

Pharmacokinetics of Choline Esters (ACh, Carbachol, Bethanechol)

Absorption: - oral bioavailability: low (they are hydrophilic and partially hydrolyzed in the GI) Distribution: - in peripheral tissues only- due to their quaternary state, the drugs do not enter the CNS Metabolism: - ACh is rapidly hydrolyzed by both acetylcholinesterase and butyrylcholinesterase which are present in plasma and tissues - Carbachol and bethanechol are resistant to hydrolysis by cholinesterases, hence biotransformation is negligible Route of Administration: - ACh and carbachol: topical instillation on the conjunctiva (eye) - Bethanechol: Oral

What type of stain would you use to identify the following gram + bacteria: Mycobacterium, Nocardia, Corynebacterium

Acid-Fast These bacteria are Gram+ but are more complex: - Mycolic acids (waxy): C60-C90 - Arabinogalactan - Lipoarabinomannan Mycolic acids - resist chemicals, including those found in phagolysosome and some antibiotics ** these mycolic acids can be used for an extra stain Stains: - Mycobacterium, Nocardia (partial), Corynebacterium (very weak acid-fast, will usually stain gram +) Acid-Fast staining DONT gram stain well - very resistant cell wall permits specific staining techniques with very strong decolorization Acid-Fast stains include: - ** Ziehl-Neelsen stain (most common) - Kinyoun stain - Auramine stain Ziehl-Neelsen staining procedure 1. Heated Aniline dye (Carbolfuchsin): colors EVERYTHING! 2. Acidified Alcohol decolorizer: not just alcohol but acidifed so washes away lipids and damages peptidoglycan (so a normal gram + will also appear colorless now, color will only be maintained if mycolic acid is present) 3. Methylene blue: counterstain is visible in decolorized cells - so need counterstain to make sure there is not an acid fast along with a gram negative or positive For these organisms you would do a gramstain first (1. crystal violet 2. Iodine 3. Alcohol decolorizer 4. Safranin) - to find if gram positive or negative ** THEN do an acid fast AFTER- acid fast will crush PG in sample so you can NOT do it first it will NOT retain a gram stain if there is no peptidoglycan

Henderson Hasselbach equation described the relationship between pKa and pH (for weak acids and bases). Explain

Acidic drugs (HA) release a proton (H+), causing a charged anion (A-) to form HA--><-- H+ + A- pH= pKa + log [A-]/ [HA] Weak bases (BH+) can also release a H+. However, the protonated form of a basic drug is usually charged, and loss of a proton produced the uncharged base (B) BH+ --><-- H+ + B pH = pKa + log [B]/ [BH+]

After a gram stain you find the bacteria is a gram-negative bacilli, coccobacilli/pleomorphs (most non-motile) and an aerobe (non-fermenter)- which bacteria could it be?

Acinetobacter sp., Moraxella sp., Francisella sp., Brucella sp., or Bordetella sp. Acinetobacter sp.: - cocci or rods (may resemble Neisseria) - oxidase -, catalase + - normal oropharyngeal flora - soil/plants - easy to grow on blood agar Moraxella sp. - often diplococcus (resembles Neisseria) - oxidase +, catalase + - normal respiratory flora - grows well on blood agar Francisella sp. - very small, faint staining - BCYE or chocolate agars + cys - 3 day incubation - oxidase (-) - diagnose via serology Brucella sp. - small, intracellular - enriched blood agar, 3 day + - oxidase + - serology (presumptive) Bordetella sp. - bordet-gengou, regan-lowe agar, 4-12 incubation - PCR often used - oxidase variable, motility variable (species-dependent)

Cholinesterase Inhibitor Toxicity

Acute poisoning Sxs and signs are due to: - peripheral muscarinic receptor activation - peripheral nicotinic receptor activation - central cholinergic receptor activation Death is mainly due to respiratory failure; bronchospasm and bronchorrhea (accumulation of fluid in the lungs) Treatment always include: - Maintenance of vital signs (assistance of respiration and administration of oxygen are especially important) - Alleviation of convulsion with diazepam - Administration of atropine (anticholinergic drug) - Administration of cholinesterase reactivator (pralidoxime)

What are some vocabulary terms used to describe adherence?

Adhesin: A surface structure or macromolecule that binds a bacterium to a specific surface receptor Receptor: A complementary macromolecular binding site on a (eukaryotic) surface that binds specific adhesins Fimbriae (pilus): filamentous proteins on the surface of bacterial cells that may behave as adhesins for specific adherence Glycocalyx: A layer of polysaccharide on the surface of bacterial cells which may be involved in adherence to a surface

Define Affinity, Potency, Efficacy, Full Agonist

Affinity= how much drug is needed to bind 50% of drug target (ex. receptors); KD concentration (abilit of drug to bind receptor) Potency= how much drug is needed to produce 50% of maximal effect of the drug; EC50 concentration (how drug binds receptor to produce a response) Efficacy= how much drug effect can be produced (relative to a full agonist) (ability of drug receptor complex to produce a response) Full agonist= produces maximal effect (Emax) - Agonist has affinity (can bind receptor) and efficacy (can produce response) and potency

Link between innate and adaptive immune responses

After a pathogen reaches a tissue--> complement activation in interstitial fluid (ex. release of proinfalmmatory C5a fragment, following C5 hydrolysis into C5a and C5b during complement activation, acts as a chemattractant for resident neutrophils among other things), cellular injury or expression of pathogen derived chemoattractant molcules at site of infection lead to phagocytic recruitment (resident neutrophils, macrophages, and dendritic cells) which home in towards affected area crawling along chemoattractant gradients, where they are activated for pathogen uptake, processing, and chemokine/cytokine production This initiats inflamm process of leukocyte recruitment to site of infection and acute phase protein syn. by liver - IL-1, IL-6, TNF-alpha and IL-8 produced by macrophages at infection site initiates the rolling, binding, diapedesis and migration of leukocytes as well as the vasc. permeability chracteristic of cell infiltr. and edema along with other cardinal signs of inflammation: some of these also contr. to acute phase protein syn by liver DCs and macrophages pick up and process antigen and migrate to closeset secondary lymphoid tissue to engage CD8+ and CD4+ T lymphocytes for antigen presentation and secrete the IL-12 required to initiate a TH1 response in the process, which is the appropriate response when dealing with viruses IL-12 also served to stimulate NK cells to secrete IFN-gamma Activated resident macrophages that remain in the tissue, along with the activated resident neutrophils, express chemokines and other soluble factors (IL-8, LTB4, and many more) that increase vasc permeability for leukocyte endothelial adhesion and extravasation (which is greatly enhanced by macrophage derived IL-1beta or TNF-alpha and is responsible for cellular infiltration, and recruit circulating leukocytes to the site of infection (circulating neutrophils first, soon followed by circulating monocytes & lymphocytes later on) *neutrophils are ill equipped to deal with intracellular pathogens

What are some classes of disinfectants?

Aldehydes: - glutaraldehyde, formaldehyde (formalin) O2-based oxidizing agents: - hydrogen peroxide, ozone, peracetic acid Halogens (chlorine or iodine): - povidone iodine, hypochlorite Phenolics Alcohols: - Ethanol, isopropanol Quaternary ammoniums: - Benzalkonium chloride Cationic: - Chlorhexidine ** What are the MOA and spectra of efficacy of these- remember what a disinfectant can kill is dependent on MOA, concentration and contact time

Cohort Studies

All participants are DISEASE-FREE at the start of the study - compares groups or cohorts of exposed and unexposed individuals ***Prospective Design*** (more common): tracks cohorts into the future (over time) to compare the incidence rates/new cases of the disease between exposed and unexposed Statistical measure: relative risk (AKA risk ratio) Ex: Interpretation: The risk of future lung cancer is 7 times greater for those exposed to asbestos compared to those not exposed **Retrospective Design: looks retrospectively at characteristics of a group, usually already diseased and compares risk factors; used less frequently **Often done with rare conditions (i.e. pediatric brain tumor) Study population (exposed/unexposed)---> Outcome/No outcome

ANS processes targeted by drugs include

All steps in nerve transmission are potential targets: - AP initiation and propagation - NT synthesis, storage and release - Receptor activation or inhibition - Termination of NT action (reuptake after release and enzymatic inactivation) ** Specificity of drugs used to target the ANS will be determined by extent of usafe of the process that is targeted - signaling processes that are common to most or all neurons will be the least specific - signlaing process that are unique to certain types of neurons will be highly specific Ex: a drug that reduces ACh synthesis would target all cholinergic neurons; this would include the entire parasympNS, preganglionic neurons of the symp sys. and symp neurons that innervate the sweat glands - On other hand, a drug that targets a subgroup of receptors; ex Beta1- adrenoreceptos will target the organs where the receptor is located (specificity is rlly important determinant of potential adverse effects)

Radial Immunodiffusion (Mancini)

Allows quantitation of antigens to which antibody is available. - May also be used for the quantitation of antibody when anti-antibody is available - Antibody is added to agar, which is poured on a plate - Wells are punded in the agar and standard amts of the test antigen are added to each well - Antigen the diffuses outwards and forms a ring of precipitation around the well - The size of each ring apprx the antigen conc. - A standard line is plotted using known antigen concentrations ** This method may be used commercially for the quantitation of many serum constituents, scuh as: - C-reactive protein - Transferrin - Cerruloplasmin - Complement components and antibody ** Main drawback= lack of sensitivity

pt c/o eye pain and blurred vision- phys prescribed latanoprost - what autonomic drug would be appropriate alternative?

Alpha agonist: make less aqueous humor

Cardiovascular effects of NE IV infusion

Alpha1=Beta1 (NO beta2) Increase in: - systolic BP (alpha1 + beta1) - diastolic BP (alpha1) - MAP (alpha1, beta1) - direct effect on HR (beta1) Decrease in: - reflex effect on HR (via vagus) - final effect on HR

Burn

An acute traumatic skin injury caused by: - heat - friction - chemicals - electric dischage - radiation Factors influencing the clinical significance: - Depth of burns - Percentage of body surface involved - Internal injuries from inhalation of hot and toxic fumes - Promptness and efficacy of therapy (fluid and electrolyte menagement & prevention or control of wound infection) Greatest threats of life: - Shock (hypovolemic and septic) - Sepsis - Respiratory failure (after inhalation injury) Depth of Burns: Superficial "1st degree" Dry and red (ex. Mild sunburn) - epidermis Superficial Parital-thickness: Blisters between epidermis and dermis (ex. Severe sunburns, Transient contact with scalding liquids) - epidermis and some dermis Deep partial thickness: Blisters (easy unroofed), Wet (after blister rupture) or waxy dry - epidermis and more dermis Full thickness: Waxy-white to leathery-grey to black, dry and inelastic - epidermis and complete dermis Deep injury, "4th degree": extends into fascia and/or muscle - Epidermis, Dermis, and Subcutaneous fat ***Examples of the last 3= Contact with extremely hot objects, caustic chemicals, electrial exposure, radition ------- Percentage of Total Body Surface Area (TBSA) involved: "Rules of Nines" - Method of estimation - Adults only - Superficial burns are NOT included > 20% of TBSA affected--> high risk of; - Hypovolemic shock - Infection --> Sepsis (with P. aeruginosa, S. aureus, Candida)

Grading and Staging of Cancer

An estimate of level of malignancy is used for: - prognosis and management Level of malignancy is evaluated in 2 ways: Grading: tumor aggressiveness (behavior); criteria A. Degree of differentiation - Evidence of differentiation: resemblance of a tumor to the normal tissue prototype (** criteria for differentiation are tissue- and organ specific Ex: - A well-differentaited squamous cell carcinoma produces considereable amt of kerating (pearls) and intercellular bridges (grade 1) - An intermediate.. (grade 2) - A poorly differentiated squamous cell carcinoma: no visible keratin and intercellular bridges (grade 3) - No histologic features of epithelial differntiation: ANAPLASTIC carcinoma (Dx is made with immunohistochemistry) B. Growth rate (rapidity) - An estimate of rapidity of growth according to the number of mitoses per unit of tissue (as per HPF) Ex, A sarcoma of: - low grade: 3-5 mitoses/10HPF - intermediate grade: 5-15 mitoses/10HPF - high grade: >15 mitoses/10 HPF C. Cellular atypia Ex: Squamous cell carcinoma of - low grade: moderate cellular and nuclear pleomorphism - intermediate: prominent cellular and nuclear pleomorphism - high grade: prominent cellular and nuclear pleomorphism, multinucleation, atypical mitoses ** Grade 1= well differentiation ** Grade 3= poor differentation (too many rapidly growing cells- NO epithelial pearls of keratinization) Staging: tumor size and spread

What are parasites?

An organism that lives on and at the expense of another organism - Protozoa: complex unicellular organisms with a defined nucleus and other organelles - Helminths (worms): multicellular organisms - Members of both groups have complex lifestyles Ex: - Toxoplasma gondii - A pair of schistosomes (worms)- common in fresh water pools where they gain access into the urinary tract, seen frequently in Dominica

Detection of Microbial Antigens

Antibody Agglutination - rapid (minutes), visual - works in treated patient - often low sensitvity - may have low specificity - qualitative - on specimens or cultures material Sandwich Enzyme-Linked Immunosorbent Assay - DIRECT ELISA= measures Antigen (Ag) - Targets 2 different epitopes on the Ag: one is immobilized Ab, captures Ag from sample, second is enzyme-labeled Ab, detects captured Ag (direct) - Quantitative, relatively quick if no culture step - On specimens or cultures material - Often more sensitive than agglutination- why? Chromatographic Immunoassay - Capillary action brings dye-conjugated Ag-Ab complex to an immobilized capture Ab- a sandwich ELISA donw backwards - aka lateral flow test - dipstick or strip formats - forms colored band or spot - rapid (minutes)- tradeoff! - qualitative - ex. Rapid strep test Fluorescence Microscopy described earlier (direct or indirect), when the analyte is a microbial product - You are lookig for microbial antigens in a tissue, smear, bacterial culture, etc.

What is important for limiting the spread of Varicella-zoster virus?

Antibody is important for limiting the viremic spread of VZV - Passive immunization with varicella-zoster immune globulin (VZIG) within 4 days of exposure is protective - Cell-mediated immunity is essential for resolving the acute disease and controlling the latent infection (these also contribute to the symptomatology) NOTE: virus causes more disseminated and more serious disease in the absence of cell-mediated immunity (i.e. in children with leukemia) and may recur on immunosuppression An overzealous response in adults is responsible for causing more extensive cell damage and a more severe manifestation (esp. in the lung) in primary infection that that seen in children ** T-cell and antibody levels decrease later in life, allowing VZV recurrence and herpes zoster disease

How changes in DNA sequence led to antigenic variation

Antigenic variation: changes outer surface of host CANT see you Ex. Mechanism of antigenic variation of N. gonorrhoeae pilin. Antigenic variation occurs via homologous recombination between the expressed locus (pilE) and a silent locus (pilS) ** Nisseria can turn its genes on and off and swap them in or out --> >1 milli variants on the cell surface --> pt must catch up this is why there are so many gonorrheal infections

Drug idiosyncrasy

Any unusual response to a drug " a genetically based, abnormal response to a drug" - this is dangerous for the pt and therefored must be considered a form of drug toxicity - unusualnees can be bc its qualitatively diff from the effects usually obsreved or bc it is quantitatively outside (above or below) the rande that includes most reponses *Incidence of these reactions is low- they are generally dose-dependent, but they only occur in genetically susceptible individuals --> In these pts, idiosyncratic rx become more severe when the dose is increased

Variable

Anything that is meadures and/or manipulated in a study or investigation Independent variable (IV): variables under the control of investigator; the predcitors and covariates that affect and outcome Dependent variable (DV): the effect that is being measured; the outcome or what is trying to be predicted -------- Types of Data: Independent Data: - unrelated data - diff groups - more commonly used in research Dependent Data: - related/paired data - same pt or same groups - Pretest/postest studies: statistically more powerful, different methodology

A pt with injury to her right calf- 5cm long laceration on R lateral aspect of her lower lef- the wound is close with sutures- wound healing proceeds over the next week- which of the following factors will be most likely to aid and NOT inhibit wound healing in the pt?

Application of sutures (facilitates healing) More facts about wound healing: - wound strength at 1 week is 10% - wound strength at 2-3 months is 70-80% - enzymes responsible for wound remodeling include: metalloproteinases (collagenases, gelatinases, stromelysins, membrane-bound forms) - vit C deficiency (scurvy) leads to poor wound healing (vit C promotes hydroxylation of procollagen) - glucocorticoids (hormones) like cortisol impede wound healing via attenuating the activation of macrophages - Basement membrane scaffolding do not perfectly regenerate, leading to imperfect epithelization - Loss of elastic fibers--> less distensible scar

Bacteriostatic Drugs

Arrest the growth and replication of bacteria at serum levels achievable in the pt, thus limiting the spread of infection, but does NOT kill them For this reason, the number of bacteria remains relatively constant in the presence of bacteriostatic drug, and immunologic mechanisms are required to eliminate the offending pathogens If the drug is removed before the immune system has eliminated the bacteria, enough viable bacteria may remain to initiate a second cycle of infection*** Since intact cellular immunity is req. to get rid of bacteria, bacteriostatic drugs are NOTTT to be used in immunocompromised pts Main bacteriostatic drugs include: - Sulfonamides (are bacteriostatic on its own) - Macrolides - Clindamycin - Tetracyclines - Chloramphenicol - Linezolid

Cholesterol Accumulation

Artherosclerosis: accumulation of lipoproteins and cholesterol within the intima of large and medium-sized vessels - Microscopically: looks like needle-like slits Xanthoma: accumulation of cholesterol in the skin - Xanthelasma: around the eyes Cholesterolosis: accumulation of cholesterol in the mucosa of the gallbladder

Examples of chronic inflammation that serve as predisposing to cancer

Asbestosis --> mesothelioma, lung carcinoma Chronic viral hepatitis (B and C)--> liver cirrhosis--> hepatocellular carcinoma Chronic H. pylori gastritis --> gastric adenocarcinoma Opisthorachiasis--> cholangiocarcinoma Shogren syndrome --> lymphoma Schistosomiases--> bladder squamous cell carcinoma Mechanisms: - Inflammatory response --> ROS production --> DNA damage - Repair/regeneration--> hyperplasia and metaplasia--> possibility of neoplastic transformation

What are the core skills of motivational interviewing?

Asking open-ended questions Making well-timed Affirmations (positive reinforcement) Making frequent Reflective Listening Statements (mirrors what pt says- "I hear you", "I am accepting, not judging you", "this is important", "please tell me more" Using Summaries to communicate understanding - "Let me summarize what we've just talked about.." - a specialized form of reflective listeing - communiates your interest in a pt, build rapport, call attention to salient elements of discussion - helps to shift attention or direction

Describe Assembly of the Herpesvirus during the lytic cycle

Assembly: Capsids assembled in nucleus on temporary scaffolds [prePR polyprotein: pAP (assembly protein precursor), AP (mature assembly protein), & PR (assembly protease)] Yields 3 capsid types: - A-capsid: empty capsid - B-capsid: capsid with disintegrating scaffold - C-capsid: capsid with DNA core ***ALL 3 contribute to formation of inclusion bodies which can be used to diagnose infection Relationship of assembly to cytopathic effects: - Herpesvirus Cowdry type A inclusion bodies - Human cytomegalovirus owl's eye inclusion - Giant multinucleated cell: syncytium (**role of gB fusion protein**)

Predominant TOne (Remember Nn on Ganglia)

At rest one division of the ANS usually exercises dominant control over various organs (predominant tone)- the effects of ganglionic blockade can be predicted if you know which division of the ANS is dominant at rest Sympathetic (adrenergic) Predominant tone in: - Arterioles---ganglionic blockade (GB)--> vasodilation; increased peripheral blood flow; hypotension - Veins---GB-> Dilation; peripheral pooling of blood; decreased venous return; decreased cardiac output Parasympathetic (cholinergic) Predominant tone in: - Heart--GB--> tachycardia - Iris--GB--> Mydriasis (pupil dilation) - Ciliary Muscle--GB---> Cycloplegia- focus to far vision - GI tract --GB--> Reduced tone and motility; constipation; decreases gastic and pancreatic secretions - Urinary bladder--GB--> urinary retention - Salivary glands--GB--> Xerostomia (dry mouth) Sympathetic (cholinergic): - Sweat glands --GB--> Anhidrosis (absence of sweating)

Acetaminophen toxicity

At therapeutic doses, 95% of metabolism is by Phase II processes (glucuronidation, sulfonation) and 5% by P450 (CYP2E1) The 5% metabolized by CYP2E1 produces NAPQI (N-acetyl-p-benzoquinoneimine), a highly reactive compound which is then conjugated with glutathione - Glutathione depleted --> free radical damage - Binding of hepatic proteins --> hepatocyte necrosis-liver failure In large doses, NAPQI depletes glutathione stores wih toxicity through two mechanisms: - direct binding of hepatic proteins by NAPQI - increased free radicals due to lack of glutathione Heavy alcohol use induces increased levels of CYP2E1, making alcoholics more vulnerable to acetaminophen toxicity at lower doses Liver necrosis starts in zone III as this has the highest concentration of cytochrome P450 Acetaminophen is the most common cause of acute hepatic failure (50%), often in suicide attempts

Abs US shows decreased size of one kidney- what term designates morphologic changes in the affected kidney?

Atrophy: - If this occurs in a pt with high BP of 160/105mmHg--> this would most likely be due to diminished blood supply

Define Atrophy and its mechanisms

Atrophy= A decrease in cell size by loss of cell substance --> A decrease in organ/tissue size when large numbers of cells are involved Classification: Physiologic atrophy and Pathologic atrophy which are both reversible to a certain degree Mechanisms of Atrophy: - Reduced metabolic activity with decreased protein synthesis (i.e. decrease in O2 and nutrient supply- ischemia) - Inadequate degradation of cytosolic and nucleur proteins via: 1. lysosomal degradation--> autophagic vacuoles --> lipofuscin accumulation 2. ubiquitin-proteosome pathway--> accumulation of proteins, often misfolded (can lead to serious disease i.e. Alzheimers)

Acute poisoning antimuscarinic drugs

Atropine has a good therapeutic index (>100) in adults, but a dose as small as 2mg can be lethal for children Sxs and signs are due to: - peripheral muscarinic receptor blockade - central muscarinic receptor blockade (tertiary amines only) Diagnosis is easy in severe cases (Why?) An IM injection of physostigmine may be used for confirmation- if signs of muscarinic activation do NOT occur after physostigmine administration, poisoning with an antimuscarinic drug is almost certain Treatment: is mainly symptomatic- Physostigmine rapidly abolishes the delirium and coma (would neostigmine help?) but is reserved for severe cases since some experts consider the drug more dangerous and no more effective than symptomatic treatment, in mild intoxication Symptomatic treatment usually includ: - maintenance of vital signs - alleviation of convulsion with diazepam - temperature control with ice and alcohol sponges Atropine Poisoning (from blocking of muscarinic receptor: - Mad as a hatter (CNS) - Hot has hell (sweat glands0 - Red as a beet (flushing) - Dry as a bone (dry mouth, eyes- from blocked secretion) - Blind as a bat (pupils too wide, getting in too much light)

Myasthenia Gravis

Autoimmune disorder caused by anti-ACh receptor antibodies. The number of nicotinic acetylcholine receptors in the neuromuscular junction (NMJ) is decreased. When ACh is release the end plate potential may be too small to trigger an action potential * The clinical features are muscle weakness and fatigability- the weakness increases with repeated use and may improve following rest Predicted effects of cholinergic drugs on pts with Myasthenia Gravis--> Pt gets stronger bc have enough/more ACh Is the effect of cholinergic drugs dose dependent? - High dose--> muscle weakness - Current builds--> depolarizing blockade

EBV uses the different phases of

B-cell development to establish a lifelong infection - diseases result from either an overactive immune response (infectious mononucleosis) or the lack of effective immune control (lymphoproliferative diseases and hairy cell leukoplakia) Productive infection of B cells and epithelial cells of the oropharync, such as in teh tonsils promotes virus shedding into saliva to transmit the virus to other hosts and establishs a viremia to spread the virus to other B cells in lymph tissue and blood NOTE: T cells limit the outgrowth of the EBV-infected cells and maintain latent infection NOTE: there is a cuasative associationwith lymphoma in immunosuppressed ppl and african childre living in malarial regions (african burkitt lymphoma) and with nasopharyngeal carcinoma in china)

What is responsible for the control of Mitochondrial pathway (intrinsic) of apoptosis?

BCL2 family Proapoptotic: BAX, BAK (act as channels that allow leakage of cytochome c into cytosol) Antiapoptotic: BCL2, BCL-XL, MCL1 (block BAX and BAK channels and prevent release of cytochrome c into cytosol) Sensors (BH-3 only): BAD, BIM, BID, Puma, Noxa (sense cellular stress and damage regulate balance between anti- and proapoptotic groups

Selective Beta1-Antagonists

BETA1 ONLY (targets heart and kindey mostly) - Atenolol - Esmolol - Metoprolol MOA: Competitive inhibition of beta1 receptors NOTE: there are NO beta2 selective drugs in clinical use- there is no obvious clinical use for them, however there is potential for harm as a result of beta2 blockade in the lung

Molecular mimicry

Bacteria try to look the same instead of changing their outter surface Numerous bacteria either produce or decorate their cell surface with host-like proteins - Fibronectin and other molecules of the extracellular matrix are common examples- deposited on numerous bacteria - Capsule of steptococcus pyogenes is made of hyaluronic acid (strep throat untreated--> acute rheumatic fever--> rheumatoid arthritis) - Sialic acid is often found on the surface of Neisseria, Haemophilus - Factor H binding (lyme disease spirochetes) **Molecular mimicry can result in autoimmune disorders

Ouchterlony technique

Based on double diffusion in agar - Wells are punched in agar and test solutions of antigen and antibody are poured into the wells - Antibody is in the center well while antigen is placed in the other wells - Both antigen and antibody diffuse towards each other and from a line of precipitation at the zone of equivalence - Thus, this technique determines the identity but not the quantity of antigen - Results are interpreted as identity, non-identity or partial identity *** this is no longer in regular use

Acessing the pts wishes

Best= direct conversation with pts If pt cannot communicate choices directly, use following options in this order: 1. Subjective standard (advance directive) - what pts said in past - living will, durable power of attorney (POA) for health care, "Do not resuscitate" orders (DNR) 2. Substituted judgment - surrogate decision maker 3. Best interest standard - what most pts in situation woud want ** Ethics committees make recommendations, but do NOT decide

What is the mechanism of action of beta-lactam antibiotics?

Beta lactam: Penicillins, Cephalosporins, Carbapenems, Monobactams 2 Principle actions: 1. Bind to specific beta-lactam receptors called penicillin-binding proteins (PBPs) located on the cytoplasmic membrane - These proteins are enzymes endowed with various catalytic fx which are inhibited by the binding with antibiotic - The most important enzymes inhibited are transpeptidases which catalyze the final cross-link step in the synthesis of murein (aka peptidoglycan) - Since PG layers are constituents of bacteria cell wall, the synthesis of this wall is blocked 2. Autolytic enzymes (called autolysins or murein hydrolases) are present in the cell wall and degrade the peptidoglycan - Beta-lactam antibiotics can activate these autolysins (apparently by blocking an autolysin inhibitor) so promoting the lysis of bacteria

How do you choose the right beta-antagonist?

Beta-antagonists can be distinguished using the following features: - Relative affinity for beta1 and beta2 receptors - Intrinsic sympathomimetic activity- some beta-antagonists have partial agonist activity (*Remember how a partial agonist behaves in the presence of a full agonist) --- partial agonist activity may prevent severe bradycardia or negative inotropy in the resting heart - Blockage of alpha receptors- adds vasodilatory properties - Local anesthetic activity- drugs with local anesthetic activity may be irritating on the eye - Parmacokinetic parameters- Esmolol is ultra short acting, when the drug is given by IV steady state conditions are achieved rapidly and the therapeutic actions of the drug are terminated soon after the infusion is discontinued

SNS effect in the heart is mediated by what receptor?

Beta1 It increases.... - heart rate in SA node - contractility and conduction velocity in atria - automaticity and conduction velocity in AV node - automaticity and conduction velocity in His-Purkinje system - contractility, conduction velocity and automaticity in the ventricle

Hektoen enteric agar (HE)

Bile salts and indicator dyes inhibit the growth of gram-positive organisms - Fermenters (sugars-lactose, sucrose, and salicin) appear yellow-orange, and non-fermenters appear green or transparent. - Organisms that produce hydrogen sulfide (H2S) from sulfate (ex. salmonella but not shigella) will form a black precipitate resulting from the interaction with ferric ammonium cirtate in the medium

CO Poisoning

Binding of CO to hemoglobin (Hb) Hb has 240-fold greater affinity for CO than for O2 Resultatant carboxy-Hb does NOT carry oxygen >20% of Hb are saturated with CO--> systemic asphyxia > 60% saturation--> unconsciousness and death (mechanism: CNS depression) Acute CO Poisoning: - Cherry-red color of skin and mucous membranes (results from high levels of carboxy-Hb) - If death occurs rapidly--> NO morphologic changes Survivors: brain changes - edema - punctate hemorrhages, mainly in the globus pallidus** and thalamus - hypoxia-induced neuronal changes Chronic CO poisoning: Once formed, carboxy-Hb is remarkably stable With persistent exposure to CO, carboxy-Hb may rise to life-threatening levels--> slowly developing brain hypoxia - Hemorrhages and necrosis of globus pallidus--> Parkinsonism (must differentiate from Parkinson Disease) Diagnosi: carboxy-Hb levels in the blood - Cessation of chronic exposure to CO--> recovery - Permanent neurologic sequelae may occur (impairment of memory, vision, hearing, and speech)

What is the Normal Physiology of Urination?

Bladder filling (Sympathetic) - Beta3: Detrusor relaxation (or block M3) - Alpha1: IUS contraction Bladder emptying (Parasympathetic): - M3: Detrusor contraction Voluntary control (Somatic): - Nm: EUS contraction US= urethral sphincter external/internal -------------------------

Deal with emotional conflict or internal or external stressors through a momentary gap in thinking, experinced as disuptive and usually followed by an embarrased reation ex. while exiting the exam, student suddenly remembers answer to question that had stumped her- A docto can recall name of disease when trying to tell pt the diagnosis

Blocking

Give an example of a differential media

Blood agar ** Differentiates hemolytic Streptococci Alpha-hemolytic: - reduction of the red blood cell hemogloin to methemoglobin--> green hue "partial hemolysis a chemical reaction" Beta-hemolytic: - total hemolysis clearing around colonies (RBC being destroyed) Gamma-hemolytic: - NO hemolysis (even though bacteria growing just fine)

Describe the system affects of Lead poisoning in Children and Adults

Blood and BM in both Children & Adults: Peripheral blood: - Microcytic hypochromic anemia, often with mild hemolysis (via inhibition of delta-aminolevulinic acid dehydratase and ferrochelatase) - Basophilc stippling in RBCs BM: - Ringed sideroblasts [red cell precursors with iron-laden mitochondria (detected with prussian blue)] ** Blood changes develop rapidly and are characteristic Nervous System: Children: - CNS, low doses --> functional defects: delay in mental dev. etc. (via abnormalities in NT due to disruptions in Ca2+ metabolism) - CNS, high doses--> encephalopathy and structural changes: brain edema, demyelination, astrocytosis Adults: - PNS: peripheral demyelinating neuropathy: wrist and foot drop **Children>adults GI both Children & Adults: - "lead colic": extremely severe, poorly-localized abd pain - blusih discoloration of the gingiva ("lead lines" *** A cause of "acute abd" Kidneys in both Children & Adults: - Injury & necrosis of PCT - Interstitial fibrosis and renal failure - Decreased excretion of uric acid ("saturnine gout") Bones Children: - Abnml remodeling of cartilage and primary bone trabecules--> increased bone density at the epiphyses ("lead lines") Adults: - Delay in fracture healing due to increased chondrogenesis and decreased cartilage ** Seen with x-ray

Differentiate between Familial vs. Sporadic Retinoblastoma (RB)

Both alleles of RB gene are affected - "two hit hypothesis" (Knudson, 1974) Familial/sporadic RB= 2/3 Familial RB - Bilateral retinoblastoma - Osteosarcoma, and soft-tissue sarcomas ** will show absence of Red Reflex Sporadic RB gene mutation: a single organ is affects (takes longer) - Unilateral retinoblastomy, or - Lung, or breast, or bladder, or skin, etc. cancer

A 40 yo woman was treated with an alpha1-agonist. What is the predicted effect on heart rate after the drug was administered?

Bradycardia From Signaling in CNS, NTs, and ANS receptors- the process that leads to Bradycardia is as follows: Alpha1--> vasoconstriction--> increased barorecptor firing--> ACh from brain --> Nn in ganglia --> M2--> heart rate slowed down ** If we were to pretreat with a drug that would increase BP (not blocking alpha) but want to prevent bradycardia--> block M2 nicotinic receptors this would take away the bradycardia (same response but somewhat changed) **Remember you can block an alpha1 agonist using an alpha1 antagonist (a direct antagonist is the easiest way to do things)--> No response

Movement of drug molecules across the membrane by pores BETWEEN capillaries endothelial cells (intercellular pores) is referred to as

Bulk flow transport - used for drugs with a high molecular weight - this is a passive and non-selective process (depending only on molecular size) ** Drugs with a MW <1500-1600 can reach the systemic circulation by bulk flow transport through capillary pores - Drgus with a higher molecular weight enter the systemic circulatin by bulk flow transport through lymphatic vessels

What are the Routes of Metastasis?

By lymphatics (lymphatogenous spread) - along natural routes of lymphatic drainage - typical for carcinomas and some sarcomas (ex. synovial sarcoma) - 1st affected nodes: regional lymph nodes -- Sentinel node= the 1st lymph node that received lymph from the site of primary tumor (identiified by lymphangiography) Next step: secondary (and tertiary, if any) barrier of lymph nodes--> the thoracic duct and right thoracic duct--> subclavian veins --> hematogenous spread (spred in blood) By bloodstream (hematogenous pread) - Venous wall is more permeable than arterial; with venous invasion the neoplastic cells follow the venous flow draining the site of neoplasm - The first wave of blood-borne metastases-- lungs for the systemic circulation, liver for the portal circulation - The next waves of blood-borne metastases: bones and bone marrow, brain, adrenals, and liver (from the systemic circulation) Tumors and organs: - All sarcomas - Some carcinomas at early stage: bronchogenic carcinoma (along with lymphatics), hepatocellular carcinoma, follicular carcinoma of the thyroid, renal cell carcinoma, choriocarcinoma (is not a carcinoma)). ** ALL carcinomas are at an advanced stage Perineural spread - Prostate and pancreas carcinoma metastisize along peripheral nerves to the spinal cord and produce pain Seeding of body cavities, surfaces and spaces - Serosal cavities: peritoneal and pleural ***Krukenberg tumors: bilatreral ovary-located metastases of gastric and colon mucus-producing adenocarcinomas - CSF spaces: malignant tumors of CNS - Along natural passages: urothelial carcinoma of the renal pelvis metastisizes along the ureter and urinary bladder

EBV in saliva infects epithelial cells and then naive resting B cells in the tonsils--> growth of the B cells is timulated first by the virus bindign to the

C3d receptor, a Bcell growth stimulating receptor, and then by expression of the transformation and latency proteins- which include: - Epstein-Barr nuclear antigens (EBNAs) 1,2, 3A, 3B, and 3C - Latent proteins (LPS) - Latent membrane proteins (LMPs) 1 and 2 - 2 small Epstein-Barr-encoded RNA (EBER) molecules, EBER-1 and EBER-2 EBNAs & LPs= DNA binding proteins that are essenital for establishing and maintaining infection (EBNA-1), immortilization (EBNA-2) and other purposes - LMPs are membrene proteins with oncoprotein-like activity - Genome becomes circularized; the cells proceed to follicles that become germinal centers in the lymph node, where the infected cells diff into memory cells -- EBV protein syn ceases, and the virus establishs latency in these memory B cells EBNA-1 will be expressed only at cell division to hold onto and retain the genome in cells NOTE: - Viral proteins produced during a productive infection are serologically defined and grouped as early antigen (EA), viral capsid antigen (VCA) and the glycoproteins of the membrane antigen (MA) - early protein mimics a cellular inhibitor of apoptosis - late protein mimics the activity of human interleukin (IL-10) (BCRF-1), which enhances B-cell growth and inhibits TH1 immune reponses to facilitate virus replication

What are the major means by which Cytomegalovirus is transmitted?

CMV is mainly transmitted via the congenital, oral, and sexual routes, blood transfusion, and tissue transplantation are the major means by which CMV is transmitted ** CMV= opportunistic--> rarely causing sxs in immunocompetent host but causing serious disease in an immunosuppressed or immunodeficient person (i.e AIDs pt) Sources of cytomegalovirus: - Neonates: transplacental transmission, intrauterine infections, cervical secretions - Baby or child: body secretions- breast milk, salive, tears, urine - Adult: sexual transmission (semen) blood transfusion, organ graft ** Babies of mothers who experience serovoncersion during term are at high risk for congenital defects CMC outcomes: -Normal pts: asymptomatic carrier or mononucleosis (heterophile Ab negative) - Neonate of seronegative mother: cytomegalic inclusion disease - AIDS, immunosuppressed: Multiple symptomatic disease

Pharmacological Effects of Antimuscarinic Drugs

CNS: After intermediate dose: - Fatigue, sedation, drowsiness - Depression of the vestibular function (blockade of M receptors in vestibular nuclei) and antiemetic action (blockade of M1 receptors in solitary tract nucleus and chemoreceptor trigger zone) (these effects are more pronounced with scopolamine) - Reduction of parkinsonian tremor and rigidity After high dose: - Amnesia, maliase, restlessness, irritability, disorientation, hallucinations, delirium. Central stimulation is followed by depression (coma) ** Old and very young pts are particularly prone to CNS effects Cardiovascular system (Heart)- M2 - SA node: tachycardia - Atria: increase in automaticity and contractility - AV node: increase in conduction and automaticity; decrease in refractoriness - Ventricles: minimal direct effects (postsynaptic muscarinic receptors are very few in the ventricles) Cardiovascular system (Vessels) - Most vessels receive no innervation from the parasympathetic system - At therapeutic doses negligible effects on circulation (but vasodilation and hypotension caused by muscarinic agonists are readily antagonized) - High doses: dilation of cutaneous blood vessels (mechanism unknown)- In children even therapeutic doses can cause this "atropine flush" GI: - Decreased tone, amplitude of contractions, peristaltic activity and secretions of intestinal tract - Relaxation of the lower esophageal sphincter (can lead to increased reflux) GU: - relaxation of bladder and ureters - slows voiding * Urinary retention= side effect Resp system: - Bronchial smooth muscle relaxation - Decreased bronchial secretions **help with breathing or runny nose Eye: - relaxation of sphincter of iris (mydriasis) - relaxation of the ciliary muscle (which leads to cycloplegia and hinders the outflow of aqueous humor through the Schlemm's canal) - decreased secretion of lacrimal glands- dry eyes Skin: - Decreased secretion of sweat glands. This decrease in raise body temperature, especially in hot climates. Infants and children are particularly prone to atropine induced hyperthermia (atropine fever)

Pharmacological Effects of Cholinesterase Inhibitors

CNS: Compounds that can enter the CNS (pharmacokinetics) may cause: - after moderate doses: increased alertness, stimulation of various central activities (activation of cholinergic receptors) - after high doses: confusion, ataxia, loss of reflexes, generalized convulsions, coma, and central respiratory paralysis (inhibition of cholinergic receptors) Eye, resp system, GI, urinary system: - quite similar to those effects of muscarinic agonists Cardiovascular system: The effects are the results of: - stimulation of sympathetic ganglia* - stimulation of parasympathetic ganglia* - release of epinephrine from adrenal medulla* - activation of M2 receptor on the heart **= preganglionic- nicotinic receptor activation Net effects depend on the dose: - After moderate doses: bradycardia (but tachycardia can occur if activation of Nn prevail) and no change or a modest fall in BP - After high doses: marked bradycardia and hypotension Neuromusclar junctio: - After moderate doses: increased strength of contraction (activation) - After high doses: fasciculation, neuromuscular blockade (inhibition)

Diseases occurs from a _____ of microbial and host response

COMBINATION - Usually it is your pt eating themselves (immune system) - Ex: streptococcus pneumonia just growing in your lungs- your immune system goes and floods it --> cough (same with TB) Bacterial- mediated pathogenesis --> secreted toxins --> somatic cell damage Host-mediated pathogenesis --> Antigens + leukocytes --> prolonged immune and inflammatory cell response

Differentiate between COX-1 and COX-2

COX-1: - expressed constitutively in MOST cells - responsible for the physiologic production of prostanoids- responsible for homeostatic functions of the GI, kidneys, also platelet function COX-2: - readily inducible, its expression levels being dependent on the stimulus - causes the elevated production of prostanoids that occurs in sites of chronic disease and inflammation - major source of prostanoids in pain, inflammation, fever and cancer **** Inhibition of COX-1 is UNDESIRABLE, whereas inhibition of COX-2 is DESIRABLE - Most NSAIDs non-selectively inhibit COX-1 and COX-2 whereas some are SELECTIVE for COX-2

How do you diagnosis Varicella-zoster virus?

CPEs in VZV-infected cells are similar to those seen in HSV-infected cells and Cowdry type A intranucelar inclusions and syncytia - Direct fluorescent antibody to membrane antigen (FAMA) test can also be used to examine skin lesion scrapings or biopsy specimens - Antigen and genome detection are sensitive means of diagnosing - PCR and genome detection techniques are especially useful for systemic and neuronal disease Isolation of VZV is not routinely done bc the virus is labile during transport to the lab and replicates poorly in vitro Serologic tests that detect antibodies to VZV are used to screen population for immunity to VZV--> antibody levels are nmlly low, so sensitive tests such as immunoflurescence and ELISA must be performed to detect the antibody -- A significant increase in antibody level can be detected in ppl experiencing herpes zoster

Effects of Cancers on the Host cell

Cachexia (wasting syndrome) - a hypercatabolic state manifested by loss of muscle tissue, muscle weakness and anorexia, with or without loss of body fat - greek "kakos"- bad and "hexis"- habit of body - a feature of advanced cancers, mainly gastric, pancreatic, lunng, and prostate carcinomas - NOT associated with food intake - Postulated mechanism: influence of cytokines produced by activated tumor-infiltrating macrophages (TNF, IL-1, and IL-6) Paraneoplastic syndromes: pathological conditions, which are associated with, but not directly related to neoplasma or their metastases - Ectopic hormone production - Other Effects on the host are major causes of death of pts with cancer (after secondary infections) *** NOTE: secondary tumors (metastases) have the same ability to produce adverse effects)

Describe Inactivated Vaccines (a type of active immunization)

Can provide a protective imune response without the risk of infection by the agent - used for agents that cannot be attenuated, may cause recurrent infection, or have oncogenic potential - when comparing inactivated vs. live attenuated vaccines, there are disadvantages and advantages to both Some disadvantages of inactived vaccines: - Immunity is not usually life-long - Immunity may only be humoral and not cell-mediated - A local IgA response may not be elicited - Booster shots are often required - Larger doses must be used Major types of inactivated vaccines: 1. Killed bacterium or inactivated virus: - microorg (bacteria or virus) is rendered incapable of causing infection- organism is inactivated chemically (ex. formalin) or with heat 2. Subunit vaccines: consists of bacterial or viral antigenic components that elicit a protective immune response a. Polysaccharide vaccines: polysaccharide capsule rigorously protects an encapsulate microorg from phagcytosis and complement - antibodies elicited against these carbs are an important part of immunity against these organisms- it is important to remember the capsular polysacc. can only drive T-independent B cell responses (rapid and can elicit a relative long-lived humoral immunity) - hence such anitgens are referred to as T-independent antigens b. Polysaccharide conjugate vaccines: - B cells activated by T-independent antigens do not req. T cell help - Conjugate vaccines are meant to elicit T-dependent B cell activation, by providing a source of T lymphocyte epitopes in form of linear antigenic peptides and coformational B lymphocyte epitopes (a wat of tricking immune sys. into making antibodies to capsular polysaccharide) - Vaccine conjugates have decreased incidence of infections with ceratin encapsulated bacteria (ie. Polysaccharide and polysaccharide conjugate vaccines are currently used to prevent infections with Haemophilus influenzae type b and Streptococcus pneumoniae - Infants, younger children, and the elderly are given the conjugate vaccine while older children and adults are given the polysacc vaccine NOTE: T-dependent vs. T-indpendent - T-dependent: isotype-switched; high-affinity antibodies; memory B cells, long-lived plasma cells - T-independent: mainly IgM, low-affinity antibodies; short-lived plasma cells 3. Other microbial subunit vaccines: Virus-like particles (VLPs are virus particles devoid of infectivity for lack of genomic nucleic acid in the particle), virus caspid protein, virus surface glycoproteins, and antigenic bacterial proteins and other components serve as the antigenic component of these vaccines 4. Toxoid vaccines: - antigenic component of these vaccines is a derivative of a bacterial exotocin- the natural toxin is chemically or genetically engineered to be a harmless version of the toxin- these vaccines are useful in preventing infectious diseases in which the pathogenesis is associated with a secreted toxin (ex. tetanus, diphtheria)

Candida can lead to opportunistic infections- overgrowth in an environment- Elaborate on this

Candida is part of our normal mucocutaneous flora (endogenous) Surface overgrowth- numerous conditions: - Diabetes: make more candida mannoprotein increasing adherence and increasing potential for invasion - Antibiotic use: decreases bacterial competition; fungi overgrow Gi tract - Moisture, hormones, stress: increased surface growth and production of cytotoxin damagin mucocutaneous surfaces (diaper rash, vaginitis)

Virulence

Capacity of infection to cause disease (often refers to the # of organisms required to cause disease) - can be measured by disease severity - can be measured by incidence (capacity to cause more severe disease in an individual, and the capacity to cause disease in greater proportions of infected hosts) Ex. of Virulence measurement: - LD50: dose req. to kill 50% of infected individuals - PD50: dose req. to paralyse 50% of infected individuals - ID50: dose req. to infect 50% of individuals) - Mean time to death, to symptom appearance - Histology/Pathology (Cytopathic effects) - Blood (ex. CD4+ counts, viral loads expressed in copies/mL or U/mL) - Biochemical markers (ex. ALT) Viral virulence mechanisms fall into 4 broad categories: 1. Gene products that alter viral or cell replication - Bone marrow suppression - Viral proteins that increase cell cycling and/or DNA synthesis (ex. Tax & HBx effects on cyclins & CDKs, as well as p53, Rb, p27, & p21 ------ increased in viral replication rate--> increased transmission, potential for cell transformation and tumor formation - RNA virus 5' RNA non-coding sequences: increase in viral replication rate--> increased transmission 2. Mechanisms that alters host defenses ** 3. Mechanisms that facilitate viral spread (increase virus capacity to replicate) 4. Gene products that are toxic Ex: - Rotavirus NSP4 enterotoxin: inhibition of glucose-coupled Na+ transport--> diarrhea - HIV gp41 protein: apoptosis of CD4 T lymphocytes

What vaccine should be given to Haemophilus influenzae type b (Hib) (pneumonia, meningitis, epiglottitis, endocarditis, & more...)

Capsule polysaccharide-protein conjugate vaccine Should be received by: - children and high-risk pts (asplenia, early complement deficiencies, other high-risk patients)

Acetylcholinesterase Inhibitors

Carbamates: - Physostigmine - Neostigmine - Pyridostigmine Alcohols: - Edrophonium Organophosphates (pesticides) - Malathion - Parathion CNS (Alzheimer drug) Drug: - Donepezil ** these all increase ACh in the synapse Cholinesterase inhibitors can be (reversible and irreversible: Reversible: - Physostigmine - Pyridostigmine - Neostigminie - Edrophonoium - Donepezil Irreversible (Inseticides/Poisons): Organophosphates: - Malathion - Parathion

Adverse effects of Beta-antagonists

Cardiovascular system: - bradyarrhythmias (bradycardia, conduction disturbances, A-V block) - acute heart failure (in pts whose CO depends heavily on sympathetic drive) - withdrawal effects after chronic use (hypertension, angina, MI, sudden death) Central NS: - Insomnia, dizziness and fatigue - Depression Respiratory system: - Increased airway resistance (beta1+Beta2)- it can be life-threatening in pts with bronchospastic disease Other systems: - Sexual dysfunction in males (the incidence may be high after chronic treatments) - Increased probability of hypoglycemic reactions (in susceptible pts) and increased effect of hypoglycemic drugs - Hyperkalemia (if not blocking beta2 you can have increased levels of beta2)

Pharmacologic Effects of Choline Esters (ACh, Carbachol, and Bethanechol):

Cardiovascular system: Heart-M2 - decrease in HR - decrease in conduction velocity in the AV node - decrease in force of contraction - decrease in force of contraction is more significant for the atria than the ventricles Vascular endothelium: - generalized vasodilation via M3-mediated release of NO. While there are M3 receptors on the vascular endothelium- remember there is NO parasympathetic innervation of blood vessels Respiratory system (M3): - Bronchial smooth muscle contraction - Increased tracheobronchial secretions Eye (M3): - Contraction of the sphincter of iris (miosis- pupil smaller) - Contraction of the ciliary muscle which leads to: 1. Cyclopasm (the lens curvature is increased and lens focuse power is adjusted for near vision- since the ciliary muscle cannot relax, accomodation for far vision is lost) 2. Widening of the spaces within the trabecular meshwork, so facilitating aqueous humor outflow through Schlemm's canal - Increased secretion of lacrimal glands Skin (M3): - Increased secretion of sweat glands Gastrointestinal system (M3): - increased tone, amplitude of contractions, peristaltic activity and secretions of GI tract - relaxation of most sphincters - contraction of the lower esophageal sphincter Genitourinary system (M3): - Increased ureteral peristalsis - contraction of detrusor muscle (which leads to a decreased capacity of the bladder) - relaxation of trigone and internal sphincter of urethra - erection in males

What are Penicillin-binding proteins (PBPs)?

Carry out various jobs in the PG biosynthetic process: - Transglycosylase - DD-transpeptidase= transpeptidase - DD-carboxypeptidase: removes last D-ala from peptide tails that have not been crosslinked - DD-endopeptidase: cleaves PG crosslinks, to allow cell growth and separation; one of several type of autolysins - Enzymes that degrade soem beta-lactam antibiotics, called beta-lactamases, are also classified as PBPs (bc they bind to penicilin) - Bacteria have many PBPs, often overlapping in function (important because PG essential) ** so figuring out how to target these proteins is very valuable

Describe Viral replication during the Lytic cycle of HerpesViruses

Cascade fashion: VP16 tegument protein stimulates immediate-early gene (alpha gene) transcription by host RNApol II Transcription of alpha genes (immediate-early)- alpha proteins responsible for the activation of beta transcription (by transactivation), modulation of the cell cycle, chromatin structure, RNA splicing and transport, blunting of innate and adpative immune responses Transcription of Beta genes (early)- Beta proteins responsble for genomr replication and stimulatin of gamma gene transcripiton - Formation of DNA replication complex [6 proteins, POL (polymerase), PPS (polymerase processivity subunit), SBB (single-stranded DNA binding protein), HP1, HP2, & HP3 (helicase-primase complex), and host proteins] - DNA replication generally by rolling-circle, yields a dsDNA concatemer that is cleaved into monomers upon encapsidation Transcription of gamma genes (late)- gamma proteins responsible for virion structure and tegument

What is diagnostic histology for a pt with Pulmonary TB

Caseous Necrosis - in a tuberculous granulomaand a giant cell (langhands) and a rim of epithelioid cells ** Grossly Caseous Necrosis gives a cheesy-like appearance Pt would present with increasing dyspnea on exertion over time and x-ray would show reticulo-nodular infiltrates in upper lobes and prominent hilar LN

What two tests- in terms of biochemical property use enzymatic activity as an identifier?

Catalase test and Oxidase test Catalase test: looks for breakdown of hydrogen peroxide to water and oxygen (2H2O2 --> 2H2O + O2) * a positive test gives bubbles Oxidase test: detects presence of cytochrome c oxidase - part of electron transport chain of some bacteria - oxidase (+)= has an ETC, so can use O2 in respiration - oxidase (-)= may have no ETC (and NOT use O2) orr may have alternate cytochrome oxidase (ans use O2) * a positive test turns purple

What is the idea of compartmental modeling?

Categorization of the number of compartments needed to describe the drugs behavior in the body One-compartment, two-compartment, and multi-compartment models: - the comparments do NOT represent a specific tissue or fluid but may represent a group of similar tissues or fluids Highly perfused organs (ex. heart, liver, and kidneys) often have similar drug distribution patterns, so these areas may be considered as one compartment: central compartment The other compartment that includes fat tissue, muscle tissue and cerebrospinal (CSF) is the peripheral compartment *If a drug instantaneously distributed to one compartment that body is considered to be behaving as one compartment (all body tissues and fluids are considered as part of this compartment) - with the 1 compartment model, there is rapid equilibrium between the drug in the plasma and some tissues and the drug concentration declines according to 1st order kinetics *When a drug distributes to some organs faster than others, the body behaves as two different compartments (drug may distribute rapidly into the blood stream and into highly perfused organs and then slowly into other tissues)

Toxoplasma gondii

Causes Toxoplasmosis - World wide prevalence - Intermediate hosts: man, cattle, rodent, etc. - Definitive host: cat family Modes of Tranmission of Toxoplasmosis: - ingestion of infected meat - ingestion of oocyst* in food - ingestion of oocyst* on hand, nail - organ transplantation - blood transfusion - accidental inoculation - inhalation - transplacental *** Toxoplasmosis is not so serious in adults who are immunocompetent BUT is dangerous in females who are pregnant it can damage the fetus

Differntiate between Herpesvirus replication at the Cellular level vs. Organismal level

Cellular level: Infection can lead to latency in CNS orr lytic replication - lytic replication could lead to death or to cell-cell transmission causing disease Orgnaismal level: - Infection can lead to Lytic replication and Switch to Latency back and forth- both lead to transmission - Lytic= most possibility of transmission ------------- NOTE: Initiation of infection: - receptor binding - membrane fusion at plasma membrane or after endocytosis - management of intrinsic responses by the tegument proteins - transport of nucleocapsid and tegument-associated IE-activators to nucles - Infection of viral genome through nuclear pores into nucleus - Genome chromatinization and initial interactions with transcriptional machinery Biological devision to become lytic or latent Latency: - restriction of lytic gene expression - expression of latency genes: management of cell and host defenses, maintenance of virus genome Can lead to reactivation into lytic replication Lytic replication: - Regulated cascade of lytic gene expression - Management of host cell: metabolism, protein synthesis and stability, cell cycle, intrinsic and innate defenses - Managment of adaptiv immune repsonses - Replication of virus genome - Virion assembly - Virion egress - Transmission to uninfected cell in the same or different host

Publich Health Surveillance

Center for Disease Control and Prevention (CDC) - partners with 57 state, local, territorial and health departments - maintains National Notifiable Disease Surveillance System (NNDSS) CDC collects and analyzes data to protect the country's health Public health emergency of international concern? Any TWO of the following criteria: (international Health regulations.. notify WHO?) - Is public health impact of the event serious? - is event unusual or unexpected? - is there sig. risk of international spread? - is there sig. risk of international travel or trade restrictions Why we do notifiable disease surveillance: - detect disease when and where it happens - stop disease before it spreads - study disease to strengthen science - improve how we prevent and control disease - keep people healthy

Give an overview of gene regulation in bacteria

Changes in DNA sequence: - Mutation - Gene amplification - Gene rearrangements (antigenic and phase variation) Transcription: - Activation - Repression Translation control: - Translation efficiency Secretion Post-translation control: - Covalent modification - Proteolysis - Binding of effectors NOTE: Regulation starts at the level of DNA- Change gene structure - Transcription rate controled - Translation modulated - Post-translational modification: protein altered after synthesis - Protein activty is modulated by the concentration of small molecules that are able to bind to their effector site

Peripheral Vascular Disease (Raynaud's Disease)

Characterized by episodes of vasoconstriction in the fingers and toes, sometimes the tip of the earlobes and nose are affected. Attacks are triggered by a decrease in temperature as well as emotional stress Vasoconstriction and ischemia could lead to tissue necrosis How would you target the sympathetic nervous system to treat the disease? - Block alpha1 (Blood vessels are too constricted so you want to dilate them to increase blood flow) - block Gq --> decrease Ca2+--> decrease constricton

Types of growth media include

Chemically defined media: - Exact composition of media is KNOWN. Usually composed of pure biochemicals off the shelf (ex. Carbon - glucose, Nitrogen-Ammonia, Sulfur-MgSO4, PO4, etc) Complex media: - Exact composition of media is not known. Contains a complex materials of biological origin (ex. blood, milk, yeast extract, beef extract) ** Most obligate human pathogens that have adapted to human growth and require complex media for growth- fastidious

Promoters of human cancer include

Chemicals: hormones (estrogens), drugs (ex: phenobarbital), alcohol, and bile salts Viral infections (i.e. EBV), etc Promoters are NOT mutagenic, i.e. they CANNOT initiate neoplastic growth - Paricipation in carcinogenesis is from clonal expansion of previously induced cells Biochemical mechanisms vary, ex: - inhibition of TGF-beta pathway - induction of hyperplasia, etc.

Who is Aspirin contrandicated against and why?

Children or teenagers with chicken pox or flu symptoms because it can cause Reye's syndrome

Differentiate between communication with children, adolescents and older adults

Children: - Detemine childs cognitive development (not age) - Develop rapport and determine what the child knows about the reason for beiing there - Explore the relationships of the child with parents, sig others, care-givers - Differentiated whether the behavior is part of a normal developmental process or might be pathological - Determine management technique Adolescents: - Tend to be more testing and distrustful - Therapeutic alliance is key - Show respect - Do not patronize - Be honest, especially with issues of confidentiality Olfer Adults: - Often anxious and may be fearful of diagnostic tests and procedures - Assess for hearing and cognitive difficulties - Self-reflect to understand counter-transference - Offer clear clinical guidance - Check for the pts understanding of the treatment plan In Summary: - Recognize the problem - Explore/consider the cause - Consider what technique to use and applit in a positive, confident manner

MOA of Aceytlcholinesterase inhibitors

Cholinesterase inhibitors are substrates for both acetylcholinesterase and butyrylcholinesterase (found in plasma and liver However almost all pharmacological effects are due to inhibition of acetylcholinesterase; which is present at high concentration in cholinergic synapses Reversible inhibitors: - Edrophonium: reversible binds to the active site of the enzyme so preventing ACh access- the bond is short-lived (2-10 minutes) bc the distribution half-life of the drug is very brief - Physostigmine, pyridostigmine, and neostigmine undergo a two-step hydrolysis similar to that of ACh. However the carbamoylated enzyme is more resistant to hydrolysis and the second step is more prolonged (1-6hrs) Irreversible inhibitors: - Organophosphates: bind to the esteratic site- the phosphorylated enzyme is extremely stabled- the phosphorous-enzyme bond is further strengthened with time by the loss of one alkyl group, a process called aging. Therefore the return of acetylcholinesterase activity depeneds on synthese of new enzymes

Pt with acute intermittent pain in RUQ after eating a fatty meal - PE: obesity, fever, tachycardia, positive Murphys sign - ABd US: distended gall bladder with wall thickening containing multiple, echogenic shadows - histology: diffuse and focal mononuclear inflamm infiltrates (lymphocytes, plasma cells, and macrophages) Dx ?

Chronic cholecystitis ** lymphoid follicles formed

After a gram stain you find that the bacteria is a gram-negative bacilli with straight rods and is a facultative anaerobe- Next you find it is lactose fermenting (CEEK)- what bacteria can it be?

Citrobacter, Enterobacter, Escherichia, or Klebsiella Citrobacter: - motile - urease and H2S (+/-) Enterobacter: - motile - urease (+/-) Escherichia: - motile - often encapsulate - urease and H2S (-) Klebsiella: - often highly mucoid - non-motile - urease (+) - H2S (-)

Lactose-fermenting Enterobacteriaceae

Citrobacter: - less commn; CNS infections in immunocompromised Enterobacter - less common; lower resp tract, bloodstream Escherichia coli - DOES NOT Produce urease - common may types of disease - disease cause is often strain-dependent - often encapsulated, motile Klebsiella - common, many types of disease - encapsulated, often highly mucoid - non-motile, produces urease "CEEK SYPS"

Countertransference

Clue: the doctor feels/acts toward the pt in uncharacteristic fashion Traditional view: - transference in reverse - qualities of past relationship attributed to the pt Contemporary (expanded) view: - tool, source of important information - jointly created: by doctors past AND by what the pt induces - especially relevant when working with personality disorders i.e. Pt who belittles you and throws out comments about skill it takes to be a surgeon (you are not a surgeon) and reminds you of your condescending older brother - most of the staff including you are troubled by feelings of wanting to show him up or even belittle him

Relative risk (RR) aka Risk ratio

Cohort studies: compare exposed with unexposed How do we estimate the magnitude of an association between exposure/risk (race) and disease/outcome (Critical Care Hospitilization)? Ratio of the incidence of disease/outcome in the exposed group (Ie) divided by corresponding incidence of disease in non-exposed group (Io) RR= Ie/Io RR= (a/ (a+b)) / (c/(c+d)) RR=1 (no difference) RR<1 (protective effect) --------- Risk ratio vs. Odds Ratio: - In some studies, we retrospectively try to determine risk (ex. case-control studies) based on disease status- can not calculate incidence)----> odds ratio - In some studies, we try to determine risk based on exposure (ex. cohort studies) prospectively --> risk ratio

"Spirit" of Motivational Interviewing includes

Collaboration (not confrontation): - physician is a partner, not an authority - motivation for change is elicited, not imposed - task is to help pt articulate and resolve ambivalence Evocation (not imposition): - draw knowledge out rather than imparting it - the pt is the expert in their own lives Autonomy (not authority): - responsibility for change belongs to the pt - the pt presents the arguments for change

How can antibiotic combinations substantially improve therapy outcome with antimicrobial drugs?

Combination are done in several infection mainly to: - treat empirically severe infections in which the cause is unknown (i.e. endocarditis) - treat mixed infection (i.e. peritoneal infections) - delay drug resistance (i.e. tuberculosis) - achieve a synergisitic effect (i.e. P aeruginosa infections) Main mechanisms of antibiotic synergism include: 1. Sequential blockade: combined use of drugs may cause inhibition of 2 steps in a bacterial metabolic pathway (ex. trimethoprim-sulfamethoxazole combination) 2. Blockade of drug-inactivity enzymes (ex. amoxicillin-clavulanate combination- Clavulanic acid inhibits penicillinases) 3. Enhanced bacterial drug uptake (ex. beta-lactam drugs increase bcaterial permeability to aminoglycosides)

Meta-analysis

Combining data from multiple studies for puprose of determining treatment guidelines - Increases statistical power and allows exploration of subgroups - provides quantitative estimates of effect: gives you a "take- home message" of a number of studies - more than a summary or literature review

Why are alcohol-based hand rubs so great?

Compared to soap and water... - Effective and quick killing of many microbes - Less damaging to skin - Faster - Bottles/dispensers can be placed at the point of care so they are more accessible *** Preferred method UNLESS hands are visibly dirty, or after bathroom use, or if a pt has C. difficile (spores can be in bathroom)

Splitting

Compartmentalizing opp affect states and failing to integrate the postiive and neg qualities of self or others into cohesive images- bc ambivalent affects cannot be experienced simultaenously, more balanced views and expectations of self or others are excluded from emotional awareness- Self and object images tend to alternate between polar opposites: exclusively loving, powerful, worthy, nurturant, and kind- or exclusively bad, hateful, angry, destructive, rejecting, or worthless

What mediator can be the reason of movement of leukocytes toward and area of microorganism accumulation?

Complement C5a & C3a & bacterial peptides these enhance "chemotaxis"

Inactivated vaccines

Components are no longer "alive"- agent cannot replicate - Can produce a protective immune response without the risk of infection by the agent Used for agents that: - cannot be attenuated - may cause recurrent infection - have oncogenic potential How to "inactivate" - formalin or other chemicals - UV light - Heat Examples: A. Killed Bacterium or Virus i.e. Inactivated whole cell vaccine for Bordetella pertussis - given in combo with diphtheria and tetanus toxoids (DPT vaccine) - high rate of side effects - acellular vaccines developed which are now recommended B. Subunit Vaccines- Recombinant i.e. Hepatitis B vaccine - comprised of hepatitis B surface antigen made recombinantly in yeast - purified protein is treated with formalin and then co-precipitated with alum (potassium aluminum sulfate) to form adjuvanted bulk vaccine C. Subunit Vaccines- Peptide or polysaccharide i.e. Streptococcus pneumoniae 2 pneumococcal vaccines - Polysaccharide capsule only - Polysaccharide capsule conjugated to diphtheria toxoid (vaccine conjugated) D. Subunit Vaccines- Toxoid - Antigenic component of these vaccines is a derivative of a bacterial exotocin - The natural toxin engineered to be a harmless version - Useful in preventing infectious diseases where the pathogenesis is associated with a secreted toxin Ex. Tetanus vaccine - Formalin-inactivated tetanus toxin - DTaP- combined vaccine for diphtheria, tetanus, and acellular pertussis

Live Vaccines

Comprised of agent that is avirulent or attenuated - Immune repsonse is similar to natural infection Attenuation (reduction in virulence)... reduction in ability to infect human cells Ex: grow virus at non-physiologic temperatures <37*C in embryonated eggs or tissue cultures --> less virulent mutants Attenuation (reduction in virulence) - poor growth at 37*C - inability to grow well in human cells - inability to escape immune control - loss of ability to infect target tissue (ex. polio vaccine contains an attenuated virus that replicates in the GI tract, but cannot reach or replicate in brain) - use an organism that provides cross-protection (ex. smallpox vaccine consists of live vaccinia virus) - genetically engineered vaccine (hybride vaccine)--> genes from infectious agent inserted into safe viruses

Cross-sectional Study

Conducted as a survery/questionnaire at one time point - exposure and outcome determined at the same time - includes exposed and non-exposed - includes outcomes (ex. diseased and non-diseased) - measures significant statistical association (correlation) *** disadvantage: cannot examing cause and effect*** - "snap shot" Selectied sample: - risk factor, disease present - risk factor, No disease - No risk factor, disease - No risk factor, No disease

Partner Notification (PN) in STIs

Contacts: PN should be discussed by medical providers with theri HIV infected pts, periodically throughout care (not just at initial diagnosis) - regulation prioritizes newly diagnosed persons with HIV - follow-up by department of health (DOG) staff will occur primarily in these cases Ex. California protocol For initial diagnosis of HIV related illness, first positive viral load or CD4<500 will be reported by labs to Health Department - providers do not need to complete a report form - if there are known contacts (including a spouse) who need to be notified, providers should contact the DOH or use a report form For inittal diagnosis of AIDs, providers should complete a report form - if there are known contacts (including a spouse), who are to be notified, proivders should use a report form, or give theri names to surveillance staff who will be actively following-up to obtain surveillance info ---- GOALS of PN: 1. Infected person: - max effective linkage to medical care, tx, prevention interventions to reduce risk for transmission to others - provide support to ensure tht pts partners are cofidentially informed of exposure 2. Partners of infected persons - max proportion of partners who are notified of their exposure - max early linkage of partners to testing, medical care, prevention, and other services 3. Community - reduce incidence and prevalence of disease by aiding in early diagnosis and tx. and provision of prevention services to infected person

How Should sexually transmitted infections be handled (i.e. Syphilis, HIV, Gonorrhea, Chlamydia, Hepatitis)

Contain the spread by.. 1. Identify individuals diagnosed - public health clinics - counseling/treatment centers - testing sites - private health clinics/providers - school clinics 2. Method of contacting affected individuals 3. Obtain information from affected individuals regarding partners 4. Methof of notifying possible affected partners

MacConkey agar (MAC) and Sorbitol MacConkey agar (SMAC)

Contains bile salts and crystal violet to inhibit growth of gram-positive organisms and some fastidious gram-negative bacteria (ex. Hemophilus and Neisseria), making it selective for some gram-negative organisms - contains lactose as the sole carbohydrate, and neutral red as the pH indicator - if organism ferments lactose, acid production lowers pH and colonies appear pink (ex. Escherichia coli) - if the organism is non-lactose fermenter, colonies will appear colorless of beige (ex. Salmonella) - can swap out the sugar for another (ex. Sorbitol MacConkey for identification of E.coli O157:H7)

Chocolate agar (CAP) and Thayer-Martin agar

Contains blood that has been heated to lyse RBCs (turns the blood brown) and release intracellular nutrients (ex. NAD, hemin) - useful for organisms with difficult nutritional requirements that cannot lyse the cells themselves, such as Haemophilus and Neisseria - a selective version of this medium called Thayer-Martin for isolation of Neisseria gonorrhoeae has antibiotics added

Tripple Sugar Iron (TSI) agar

Contains lactose, sucrose, a small amount of glucose, protein digest, sodium thiosulfate, ferrous iron, and pH indicator - location of yellow color change (from original pink) indicates: no yellow--> no sugar utilization entire tube yellow--> fermentation of multiple sugars butt only, glucose fermentation only (aerobic use of peptides produces ammonia, neutralizing the top) H2S production produces a black precipitate

Injuries produced by Mechanical Trauma include

Contusion (bruise): damage to blood vesels with extravasation of blood into tissues; produced by a blunt object Abrasion: a wound produced by scraping or rubbing Avulsion: a forcible separation or detachment (a type of severe abrasion) Laceration: a tear or disruptive stretching of tissue caused by application of force by a blunt object - intact briding blood vessels*** - jagged, irregular edges** Incision: a wound produced by a sharp instrument - bridging blood vesels are severed*** - even edges** Puncture wound: caused by a long narrow instrument - Penetrating: an instrument pierces the tissue - Perforating: an instrument traverses a tissue to create an exit wound

Cultrual Spectrum

Cultural Awareness: - Acknowledges differences - Doesnt seek broader context or understanding - Very limited behaviour change Cultural Sensitivity: - Acknowledges diff ways of seeing the world - Integrates some changes in practices or behaviour Cultural Competency: - System elements are aligned with and respecxt other cultures - Represents action of the part of an individual or organization Cultural Humility: - A lifelong commitment to self-evaluation to redress power imbalances - Develop & maintain respectful relationships based on mutual trust Culture= System of beliefs, values, rules, and customs that is shared by a group and is used to interpet experiences and direct patterns of behavior - plays a large role in shaping each individuals health-related values, beliefs, and bahaviors, and clearly impacts clinical care - includes ideas about illness and healing ** it is fluid and often invisible to you **

After a gram stain you find that a bacteria is gram-positive bacilli, non endospore forming and anaerobic- what types of bacteria may it be

Cutibacterium, Lactobacillus or Actinomyces Cutibacterium: - chains or clumps, short rods - common on skin, vagina, oropharynx - acne, opportunistic infections - formerly Propionibacterium Lactobacillus: - part of normal flora (mouth, vagina, GI) - rare pathogen (endocarditis, septicemia) - strict or aerotolerant - catalase (-) Actinomyces - filamentous, branching - catalase (-) - part of normal oral, GI flora - cervicofacial infections most common - knot up into yellow flecks visible in pus ("sulfur" granules")

What is the most prevalent viral cause of congenital disease?

Cyomegalovirus (CMV) - 15%= stillborn - 1% infected before birth - large percent infected in first months of life - 80% may shed virus for long periods by will be asymptomatic, 0.1% will have permnant CMV-related problemds Signs of disease: - small size - thrombocytopenia - microcephaly - intracerebral calcification - jaundice - hepatosplenomegaly - rash (cytomegalic inclusion disease) * Vision and hearing loss & mental retardaition are comon consequences of congenital CMV infection ** Risk of serious birth defects is extremely high for ingants born to mothers who has primary CMV infections during their pregnancies Fetuses are infected by virus in mothers blood (primary infection) or by virus ascending from cervix (after recurrence) -- sxs of congenital infection are less severe or can be prevented by the immune response of a seropositive mother Congenital CMV infection is best documents by isolation of the virus from the infants urine during the first week of life

What is the histolofical hallmark of CMV (cytomegalovirus) infection?

Cytomegalic cell, which is an enlarged cell (25-35 mm in diameter) that contians a dense, central, "owls eye", basophilic intranuclear inclusion body - Such infected cells may be found in any tissue of the body and in urine and are though to be epithelial in origin ** Inclusions are readily seen with Papanicolaou or hematoxylin-eosin staining Lab tests used for Diagnosis: Cytology & histology: - "owls eye" basophilic nuclear inclusions body antigen detection - in situ DNA probe hybridization - PCR Cell culture: - Cytologic effect in human diploid fibroblasts (slow) - Immunofluorescence detection of early antigens (faster) - PCR (faster) Serology: - Primary infection *** Samples taken from analysis include: urine, salive, blood, bronchoalveolar lavage specimens, and tissue biopsy specimens

Dopamine receptor affinities

D1>> Beta1>>>alpha1

What are the mechanisms of Mitochondrial damage (a mechanism of cell injury)?

Decreases O2 supply, toxins and raditions can lead to mitochondrial damage or dysfunction Major mechanism: sustained opening of mitochondrial permeability transition pore Consequences: - Loss of proton gradient --> NO ATP generation--> necrosis - Also an increase in the generation of free radicals (ROS) can lead to necrosis Also a decrease in survival signals and DNA and protein damage can lead to an increase in pro-apoptotic proteins leading to leakage of mitochondrial proteins (like cytochrome c)--> activates caspases--> apoptosis

Attachment Theory

Deep and supportive bond between child and caregiver/other sig. persons - safety and stability and meeting phys. and emotional needs Patterns forms as brain developes (~3 months b4 birth and throughout infancy) 4 Styles: 1. Secure - peaks at 2-8 months - essential for healthy neurological deve. - mother leaves room--> cry--> cry stops when mom returns ** Stranger anxiety * Separation anxiety Behaviors to foster this: - Sucking, Cuddling, Smiling, Crying - If infant cries/track with eyes--> signals ensure cargiver respond and meet their needs - consistent, sig. adult - reg. by predictability Allow for ability to foster healthy, meaningful future social interactiona Negative attachment behaviors 2. Ambivalent/resistant - Mix rxs to mom 3. Avoidant/insecure - No distress when separated, ignores mom when returns 4. Distorted/disorganized - disorganized behavior when mom left room, also on her retunr, not soothed if made contact with mom **These neg ones occur when: - bbys signals met with litter, irreg. or no response (ex. due to limited parental emotional or physical availability) --> bby learns that her needs may not be met through communication with others Neuropsychiatic causes of abnormal attachment: - neuro-sensory impairment (ex. cerebral palsy following birth asphyxia) - autism spectrum disorder - early physical and occupational therapy may improve outcomes and foster attachment (ex. "early steps program in fl")

Describe the main features of overdose toxicity of a drug

Defined as an adverse effect appearing after the administration of doses higher than the therapeutic dose - Overdose toxicity of drugs depends mainly on the administered dose (seriousness of overdose directly proportional to administered dose) 2 kinds of overdose toxicity: 1. Interaction with drug receptors: toxic effect is an extension of the therapeutic effect or of a side effect and therefore this is the most freq mechanism ex: hemorrhage due to anticoagulants, cardiac failure due to beta blockers, coma due to hypnotic drugs, paralytic ileus due to anticholinergic drugs 2. Cytotoxic: due to unspecific cell damage produces by the drug or (more often) by highly reactive intermediates made during the biotransformation of the parent compound - these intermediates can form covalent or non-covalent bonds with biological macromolecules, which can lead to cytotoxic effects (ex. breakage of cell membrane, block of enzymatic rx, etc.) that can cause cell death Ex: nephrotoxicity and ototoxicity due to aminoglycoside antibiotics, the hepatotoxicity due to isoniazid, the cardiotoxicity due to tricyclic antidepressants, etc.

Deal with emotional conflict or internal or external stressors by refusing to acknowledge some painful aspects of external reality or subjective experience that would be apparent to others- the term psychotic denial is sed when there is gross impairment in reality testing

Denial

Pearsons Correlation

Describes disease in relation to some factor of interest (ex. age, length of contraception use, health utilization) denoted by r coefficient Data should be independent Independent and Dependent variables should be interval or ratio Assess the strength of linear relationships Positive correlation: as one variable increases the other increases Negative corr.: as one variable increases, the other decreases No correlation: no connection between the 2 variables

List the general approach to autonomic questions

Desired or observed physiological action/effect (remember to consider reflex actions when appropraite)--> Symp or parasymp --> receptors that control physiological action --> Drug (agonist or antagonist) at appropriate receptor

Culture-Independent Diagnostic Tests (CIDTS) include

Detection of Infectious Agents - Direct microscopic examination (visualization) - Detection of a specific microbial product Detection of specific antibodies against a particular pathogen

Coagulase test

Detects enzymes which convert fibrinogen to fibrin; Staphylococcus aureus and Yersinia pestis are positive. Two types of coagulase and coagulase tests exist. If either is positive, then the organism is considered coagulase positive Free coagulase - secreted from bacterial cell - identified with tube coagulase test - secreted bacterial coagulase reacts with prothrombin in the liquid test tube medium to form staphylothrombin, which catalyzes the conversion of fibrinogen within the medium to insoluble fibrin, causing the medium to gel Bound coagulase (clumping factor) - attached to bacterial cell wall - tested with slide coagulase test or coagulase agglutination test - enzymatically converts fibrinogen (attached to latex beads) to insoluble fibrin, causing bacterial cells and beads to clump Slide: takes a few minutes Tube: overnight

Catalase test

Detects presence of catalase enzyme, which converts hydrogen peroxide to water and oxygen (2H202--> 2 H2O + O2); anaerobes are less likely to produce catalase (but several do). Most helpdul in differntiating gram-positive bacteria Test time: rapid- under a minute * postive test= bubbles

Oxidase test

Detects the presence of "cytochrome c oxidase" a component of some electron transport chains, which will turn a particular indicator purple - Some bacteria with an ETC have a different molecule replacing cytochrome c oxidase, and will test negative - helps to differentiate groups of gram-negative bacteria * result is rapid-under a minute

Urease test

Detects the presence of the urease enzyme which breaks down amides (urea), producing ammonia which will result in an alkaline pH and a color change to pink - can be agar slant or broth - Useful for identifying Helicobacter, proteus, ureaplasma, nocardia, and cryptococcus

How do we study disease

Did investigator assign exposure? Yes? --> Experimental study --> if random allocation- randomised controlled trial, if not= non randomised controlled trial No? --> Observational study--> comparison group? - if yes--> analytical study - if no--> descriptive study For analytical studies think of direction: - Cohort study: exposure --> outcome - Case-control study: exposure <----outcome - Cross-sectional study: exposure and outcome at same times Observational studies include: - Case report - Case series - Case-control - Cohort - Cross-sectional - Ecological study Experimental studies: - Randomized control trial

What are some factors that can affect antimicrobial therapy outcomes?

Direct cytotoxicity - some antibiotics can cause dose-related cytotoxicty to some organs or tissues (i.e. ototoxicity of aminoglycosides, anemia with chloramphenicol, etc.) Allergic reactions: - some antibiotics or their metabolites have the intrinsic ability to induce hypersensitivity- the most allergenic antibiotics are penicillins, sulfonamides and tetracyclines Drug interactions: - interactions sometimes occur between antimicrobial and other drugs- they are mainly due to induction (i.e. by rifampin) or inhibition (i.e. by erythromycin) of metabolism of the concomitant drug Cost: - Efficacy of specific antibiotic weighed against acquisition cost Superinfections: Broad spectrum antibiotics can lead to alteration of the nml microflora of respiratory, intestinal and GU tracts, leading to opportunistic infection (c. diff overgrowth in GI) Main antibiotics that cause superinfections are: - Fluoroquinolones (most common) - Broad sprectrum penicillins - Cephalosporins (3rd, 4th and 5th generations) - Clindamycin

Describe the Basic flow of Laboratory Diagnosis

Direct examiniation of pt specimens for presence of etiologic agents - results same day, "preliminary report" - microscopy, rapid antigen tests, nucleic acid tests, serological techniques; for blood often also CBC, blood chemistry, liver/renal function - may provide definitive diagnosis Growth and cultivation (culture) of the causative agent from the same specimens - by day 2-3, some identifying info available, "interim report" - growth characteristics, staining, rapid biochemical or antigen tests designed to be carried out on isolated bacteria Analysis of cultured agent to establish identification and other characteristics - definitive ID/susceptibilities can take a few more days; "final report" - microscopy, biochemical, antigen, nucleic acid, mass spectrometry, antibiotic susceptibilities

Types of spread of malignant tumors

Direct spread: local invasive growth into adjacent tissues - an important (but not the main) sign of malignancy - "locally malignant tumors" spread only into adjacent tissues (ex. basal cell carcinoma of the skin- metastisizes in 1% of the cases) *** Some benign neoplasms can spread in the surrounding tissues; ex. hemiangioma Distant spread Direct--> Distant spread: Local invasive growth of neoplastic cells--> Infiltration of blood/lymph vessel wall, peripheral nerve sheath, and serosal surfaces (direct spread)--> Distant spread with blood, lymph, or CSF flow --> Cell survival and multiplication --> Formation of a secondary isolated neoplasm (metastisis)

How do viruses cause disease?

Direct viral cytolysis/ Direct cytopathic effects - can also be due to indirect pathogenic effects- due to the hosts immune response ** More often than not, the pathology associated with viral disease is a combination of viral a cytopathic effects and the immune response to infection Cytopathic effects include: - Syncytia - Inclusion bodies - Vacuolization - Lysis - Apoptosis - Immortilization (cell transformation) - Rounding and loss of contact inhibition Cell-mediated immunity (CTLs, NK cells) Toxicity Cell transformation

Epidemiology of Varicella-Zoster Virus

Disease/Viral factors: - Virus causes lifelong infection - Recurrent disease is a source of contagion - Transmitted mainly be resp. droplets but also by direct contact At risk: - children (5-9) experience mild classic disease - teens and adults at risk of more severe disease with potential pneumonia - immunocompormised ppl and newborns are at risk for life-threatening pneumonia, encephalitis, and progressive disseminated varicella - elderly and immunocompromised ppl are at risk for recurrent disease (herpes zoster- shingles) - Virus is found worldwide, no seasonal incidence Antiviral drugs are avialble - immunity may wane in the elderly population - varicella-zoster Ig is available for immunocompromised ppl and staff exposed to virus, as well as newborns of mother showing sxs withint 5 days of birth - Live vaccine (Oka strain) is available for children (varicella) and adults (zoster)

Caseous Necrosis

Distinct form of necrosis with loss of tissue architecture and cellular outlines, but firm in consistency Etiology: **M. tuberculosis, histoplasma, etc. Mechanism: death of macrophages laden with microorganisms Gross appearance: white (yellow), granular and friable= "cheese-like" (latin "case"- cheese) Histology: eosinophilic structureless material

Pharmacokinetics of Cholinesterase Inhibitors

Distribution: - Physostigmine enters the CNS - Organophosphates enter the CNS - Donepezil enters the CNS - Neostigmine, pyridostigmine and edrophonium do NOT enter the CNS Half-life: - Edrophonium: 1-10 minutes (short) - Physostigmine, pyridostigmine and neostigmine 1-3 hrs (long)

Pharmacokinetics of Antimuscarinic drugs

Distribution: - Tertiary amines (atropine, scopolamine, solifenacin, benztropine) distribute to ALL tissues; including the CNS - Quaternary derivatives (glycopyrrolate and ipratropium) do NOT enter the CNS bc they are positivelly charged

What is the next step in identification, after finding a bacteria is gram-positive cocci

Do a catalase test Catalase positive --> Staphylococci (facultative anaerobe) Catalase negative--> Streptococci/Enterococci (anaerobes) Staphylococci can then be either Coagulase + or - Coagulase (+): Staphylococcus aureus - Normal flora on skin, in nares - Colonies often yellow - Beta-hemolytic - Salt tolerant - Produces acid from mannitol Coagulase (-): - CoNS - Normal flora on skin, nares, vagina - Most non-hemolytic S. epidermis - Novobiocin susceptible S. saprophyticus - Novobiocin resistant

Echinococcus granulosus and Echinococcus multilocularis

Dog tapeworm Hydatid disease (hydatid cyst) Mode: accidental ingestion of eggs Disease: Hydatid cysts in tissues Diagnosis: lesions on x-ray or scan ** Be able to identiy Hydatid cyst

How is haloperidol a competitive antagonist at the D2 receptor?

Dopamine (agonist) acts at D2 receptor (increased effect with increasing concentration of dopamine) Haloperidol (at both 1-100micromolar conc) - dopamine is added at increase concentrations - it can still have maximal effect, but curve is shifted to right (on Effect (%max) vs. Dopamine concentration (log) curve ** So with a competitve antagonist- you need more agonist to get an effect

Ethanol

Dose-Effect Relationship: Legal definition of drunk driving in the US: 80mg/dL in venous blood - Drowsiness at 200mg/dL - Stupor at 300mg/dL - Dose increases --> coma and respiratory arrest ** Chronic alcoholics can tolerate levels of up to 700mg/dL ---> Reason: accelerate ethanol metabolism caused by a 5-10 fold induction of liver CYPs Ethanol Metabolism: Ethanol--> Acetaladehyde by alcohol dehydrogenase (ADH) in the liver - <5% of acetaldehyde--> to acetate by acetaldehyde dehydrogenase (ALDH1&2- 2 forms!) High ethanol levels metabolized by microsomal ethanol oxidizing system (MEOS) Acute Ethanol Intoxication: - CNS: slurred speech, nystagmus, disinhibited behavior, incoordination, unsteady gait, memory impairment, stupor and coma - Liver: alcoholic hepatitis (***Mallory Bodies) - Stomach: acute gastritis and ulceration Esophagus: - Mallory- Weiss syndrome**: tears (mucosa, submucosa) of distal esophagus due to retching - Beorhaave syndrome: rupture of distal esophagus due to retching Chronic Alcoholism - Alcoholic liver disease, forms fatty liver (steatosis)--> alcocholic (steato)hepatitis--> liver cirrhosis - Pancreas: risk of acute and chronic pancreatitis - Heart: dilated cardiomyopathy, hypertension - CNS (not direct effect): thiamine deficiency--> Wernicke-Korsakoff syndrome - Fetal alcohol syndrome (growth, retardation) - Increased risk of cancer: oral cavity, larynx, and esophagus ***ALDH2 (alcohol dehydrogenase 2) mutation--> esophageal carcinoma

Dose vs. Concentration

Dose= weight of drug (i.e. 1-2 tablets of Acetaminophen (500mg-650mg)= dose for headache Concentration: weight per unit of volume (take drug absorbed intestines --> tissues (dissolved/aqueous= concentration in extracellular fluid) - this is what tissues are exposed too *** Drug action depends on drug concentration - too low: ineffective drug - too high: toxicity - just right: clinical benefit (without too much adverse afffects/toxicity)

Topical application

Drug applied for action on the skin- used when a local effect is desired Absorption pattern: - primarily by lipid diffusion - variable: affected by the condition of the skin, area of application along with other factors Advantages: - suitable when local effect of drug is desired - may be used for skin, eye, intravaginal and intranasal products - easy for pt Disadvantage: - some systemic absorption can occur - unsuitable for drugs with high molecular weight or poor lipid solubility

Define drug elimination, clearance, and total clearance

Drug elimination: is the IRREVERSIBLE removal of drug from the body - 2 major sites of drug elimination= kidneys & liver Clearance: the volume of fluid cleared for drug from the body/unit time (ex. units ml/min) Total clearance: reflects ALL mechanisms of drug elimination - Removal (or excretion) of drug into the urine represents renal clearance - Within the liver, biotransformation of parent drug to one or more metabolites may occur, or excretion of unchanged drug into the bile, or both CLt= CLh + CLr + CLother (h=hepatic, r=renal, other=other type of clearance)

Define Drug misuse, Drug abuse, Physical dependence

Drug misues: use of substance for purpose not consistent with legal or medical guidlinees (ie. taking higher dose than what was prescribed or taking an antibiotic that was prescribed for previous condition) Drug abuse, Drug addiction, and substance use disorder: reptitive drug taking for recreational purpose - drug craving and compulsive seeking behavior Addiction is related to the rewarding propertied of the drug, occurs only with drugs that have those properites, either bc of direct positive effects, or bc of negative effects associated with the absence of the drug - Positive effect is pharamcological; (i.e. euphoria or anxiolysis) in the CNS Main variables that affecti addicaiton are: 1. dose of the drug 2. Development of tolerance 3. route of administartion (more powerful when immediate) i.e. IV administration> oral 4. frequency of administration (must be given repetitively) ** Nicoting, cocaine, amphetamine, ethanol and opiods- reliably activate the mesolimbic dopamine pathway in the brain- "reward pathway" --> euphoric effects are mediated by increased extracellular dopamine levels in the nucleus accumbens, a brain region important in the reward pathway Physical dependence: req. continued adminstration to prevent withdrawal - tolerance is a component: needing more drug to get same efffect * phys dependence can occur with many drugs that do not cause addiction; including sympathomimetic vasoconstrictors, nitrate vasodilators, antiepileptic drugs and some antidepressants Ex: of processes that reset homeostatic mechanisms include increased/decreased expression of specific genes *** Withdrawal syndrome from given drug is often characterized by sxs opposite to those produced by drug itself- Ex: - heroin, ethanol, benzodiazepines is mainly excitatory - cocaine and amphetamine profound fatigue and depression

Ephedrine

Drug occurs in various plants of the Ephedra genus. It is found in Ma Huang, a popular herbal medication MOA: - activation of alpha1, alpha2, beta1, and beta2** receptors - enhances release of NE from adrenergic neurons Pharmacodynamics: - Peripheral effects are similar to those of epinephrine. Differences are: 1. a much lower potency 2. a longer duration of action 3. oral activity - central effects similar to, but much less pronounced than, those of amphetamines Clinical uses: - Anesthesia-induced hypotension - Pseudoephedrine is available over-the-counter as a component of some decongestant mixtures

von Hippel-Lindau Syndrome

Due to Germline loss-of-function mutation in VHL gene, chr. 3p can be seen in: - Hemangioblastomas in cerebellum, brain stem, spinal cord, etc - Renal cell carcinoma - Renal cysts - Pheochromocytoma Spontaneous mutation in VHL gene--> Sporadic Renal Cell Carcinoma

Serologic tests for antibody to viral antigens are a more dependable method than heteophile antibody to confirm the diagnosis of

EBV mononucleosis It is indicated by the finding of: 1. IgM antibody to the VCA 2. Persence of VCA antibody and the absence of EBNA antibody 3. Elevation of antibodies to VCA and early antigen (finding of both VCA and EBNA antibodies in serum indicates that the person had a previous infection) - Generation of antibdoy to EBNA req. lysis of the infected cell and usually indicates T-cell control of active disease NOTE: There is NO effective treatment or vaccine for EBV disease-- ubiquitous nature and asymptomatic shedding make control difficult --> infection elicits lifelong immunity- so best means of prevenitng infectious mono is exposure to virus early in life bc the disease is more benign in children

Requirements of a Good Vaccine

Effective, safe, stable, and low cost Effectiveness - induces a good immune response, but the response should be of the appropriate type Ex: - response that primarily induces antibody production would have limited effectiveness against certain intracellular organsism--> i.e. effective vaccine against Mycobacterium tuberculosis that stimulated anitbody production would not limit the intracellular growth and persistence of infection- for this organism, T cell immunity is imperative for successful elimination of the pathogen, so an effective vaccine would need to drive strong T cell response - for some organisms- infection best held at bay by opsonizing antibodies (i.e. Streptococcus pneumoniae)- An effect vaccine would need to strongly promote production of IgG - Mucosal immunity is important for protection against pathogens that are acquired through ingestion or inhalation- for these pathogens, an effective vaccne would need to drive formation of IgA - With some pathogens, damage to the host is mediated by the immune response against the pathogen- by trying to eliminate the pathogen, the host damaged itself- for these an effective vaccine might need to carefully balance inducetion of cell-mediated immunity - Depending on purpose of the vaccine (i.e. if its intended to protect travelers who have short-lived exposure to pathogen or inteded to give life-long immunity to pathogen), an effective vaccine may need to drive the formation of immunologic memory, not just a short-lived primary antibody response Safety: Vaccines are submitted to rigorous quality control and animal trials prior to usage in humans Common safety issues: - insufficient attenuation of live pathogens or reversion of attenuated strains to wild-type - contamination by chemicals, toxins, or other infectious agents - fetal damge, allergic reactions, autoimmunity Stability: - Most "user-friendly" vaccines can be stored at room temp (or warmer, depending on climate) for long periods of time - As there may be great distance between vaccine supplier or storage location and the pt, vaccine stability can have sig impact on availability of vaccine to pts Low Cost: - Must be easy available worldwide to have a great impact - i.e. In U.S. the cost of a 3-dose Hepatitis B vaccine can rang 75-165$- this cost is well outside of the health budgets in resource-poor countries, where disease burden is often the highest - Fortunately, governmental and philanthropic program exist to subsidize these costs in order to make these vaccines available

Vaccine requirements

Effectiveness: Induce a good immune response of the appropriate type - req. for cell-mediated immunity - opsonizing Abs (IgG) - mucosal immunity (IgA) - immune response against pathogen resulting in host damage - purpose of the vaccine (short vs. lifelong immunity) Safety: common safety issues include - insufficeint attenuation of live pathogens or reversion of attenuated straings to wild type - contamination by chemicals, toxins, or other infectious agents - fetal damage - allergic reactions - autoimmunity Stability: - long shelf life - heat stable so that it can be transported to endemic areas with warmer climates Low cost: - worldwide availability - resource-poor countries: governmental and philanthropic programs subsidize costs

RNA Human T-cell Leukemic Virus (HTLV-1)

Endemic for Caribbean basin, Japan, South American and Africa Viral Tax oncoprotein --> polyclonal T-cell proliferation--> monoclonal T-cell proliferation Induced tumor: T-cell leukemia/lymphoma + Tropical spastic paraparesis (weaknes of the arms or legs with muscle spasm)

Healthcare-acquired infections (HAIs) can be

Endogenous (from within pt)- i.e. normal microbiota or asymptomatic carriage or Exogenous (from another pt, healthcare worker, hospital environment) Causitive Agents of HAIs: - C. difficile (12%) - S. aureus (11%) - Klebsiella sp. (10%) - E.coli (9%) - Enterococcus (9%) - P. aeruginosa (7%) - Candida (6%) - Streptococcus (5%) - CoNS (5%) - Enterobacter (3%) - other (23%) Impact of HCA/HAIs: - most lethal= pneumonia, bacteremia - decreases HCA infections and MRSA over the years due to increased infection control - huge economic cost: $55 billion in US in 2008

After a gram stain, you find that the bacteria is a gram-positive bacilli- what should you determine next

Endospore-forming vs. Non-endospore-forming Endospore-forming: - Aerobe? Bacillus - Anaerobe? Clostridium Nonendospore-forming? - Aerobe? Corynebacterium or Nocardia - Facultative anaerobe? Listeria - Anaerobes? Cutibacterium, Lactobacillus, Actinomyces

After a gram stain a bacteria is found to be a gram negative bacilli with straight rods and a facultative anaerobe that is oxidase negative which bacteria may it be

Enterobacteriaceae - ferment glucose - normal GI flora - many species of medical imporant - serratia can be lac (+/-), often produces red pigment

Herpesviruses Structurs

Envelope - host derived lipid membrane with multiple glycoproteins on the surface (glycoproteins all cooperate with different stages of replication cycle) - gB, gD, gH/gL, gC, gN, gE-gI ** gC, gB, gD, gH/gL (are the most important!) Tegument - Pre-synthesiszed proteins (sometimes >20) carried into cell whose functions are to re-direct host cell process (ex. shut down host cell protein synthesis ,inhibit host antiviral cellular defenses, stimulate viral gene expression) - proteins that direct host response to infection - Consists of outer and inner tegument - Inner tegument: closely associated with nucleocapside - Outer tegument: closely associated with viral envelope glycoproteins Capsid Icosadeltahedral: - 150 hexons & 11 pentons (makue up the Major Capsid protein (which is an antigen to which diagnostic tests are directed)--- 163 capsomeres (150 hexons & 11 pentons), one of which serves as a portal (capsid portal protein/portal capping protein) for DNA packaging and release (~125nm in size) - 1 capsid portal complex - 320 triplexes ** Capsid has a valve/ door when the nucleocapsid approaches nucleus by nuclear pore this door serves to eject the virus into the nucleus - pore serves to insert DNA into capsid when virus is being assembled (Fitting of the UL6 protein into a vacant vertex in the HSV-1 capsid) Capsid Portal Complex: - Capsid portal protein (PORT; UL6) - Portal capping protein (PCP; UL25) DNA Core - dense core (nucleocapsid) dsDNA - linear dsDNA (124-295kb) packed in form of a torus **Herpes viruses are among the bigger viruses (Virion size varies from 120-260nm)

Describe viral envelopes

Envelope: protective layer - only some families have these- and it is important to know which!!* Composition: - host membrane (lipid raft) - host and viral proteins/glycoproteins Functions: - adhesion (spike glycoproteins) - protection of nucleocapsid - fusion (cell entry)

Why is epinephrine useful for anaphylactic shock?

Epinephrine activates alpha1, beta2, beta1 receptors - alpha1 and beta1 work to increase BP via vasoconstriction - beta2 does bronchodilation to help with breathing - alpha1 helps to decrease swelling via vasoconsriction- pull blood out of tissue so it shrinks Adverse effect: epi --> increases blood glucose--> liver glycogenolysis - and pupils dilated via alpha1 **we dont use norepi bc it does not hit beta2 (only epi does that) NOTE: sxs of anaphylactic shock include: - inflamm of mucosa - vasoconstric of lung - decreased BP - difficuly breathing- swollen tongue and throat * death results from inability to breathe

Pathology: The Study of Disease (Greek "pathos"- suffering) includes:

Etiology (Greek "aitia"-cause): factors that cause a disease Pathogenesis: Mechanisms of disease development Morphologic changes: Structural alterations caused by a disease - Gross (macroscopic) appearance: changes seen by a naked eye - Histologic (microscopic) appearance: changes seen by an armed eye Functional derangements: as background for clinical manifestations Clinical manifestations: - Symptoms: a patient feels - Signs: a physician discovers Other aspects: - Complications - Causes of death - Outcomes - Prognosis for recovery and life

What are some causes and examples of pathologic hyperplasia (increase in cell number)?

Excessive hormonal stimulation - Benign prostate hyperplasia (normal diameter less than 4cm, can be greater than 6cm when enlarged) - tunica muscularis increases in size to aid pt in urination - Endometrial hyperplasia - Gynecomastia - Polycythemia (increase in amount of RBC) in renal cell carcinoma (erythropoietin production)- this is opposite to anemia - Cushing syndrome in ACTH-producing tumors Growth factor stimulation - Wound healing with endothelial and fibroblast hyperplasia - Compensatory hepatocyte hyperplasia after partial hepatectomy (liver regenerates bc of proliferation of hepatocyte, never gains previous size and function will be impaired) Antigenic stimulation - hyperplasia of lymphoid tissue (ex. Infectious mononucleosis) Persistent influence of a stressor - Ex. Bronchial gland hyperplasia in chronic smokers

Transposition

Exchange of genetic information via mobile genetic elements Process: Transposon with inverted repeats enters into the recipient site - transposons can jump from one place to another on a DNA molecule (jumping genes!) - transposons may replicate while moving, resulting in a greater number of transposons in the cell - transposons can jump to plasmids and be transferred to another cell * DNA can move itself (non-replicative) or copy itself (replicative) into new places: - happens within same cell - plasmid to chromosome - chromosome site to chromosome site

Clinical application of Antimuscarinic Drugs:

Eye: - Funduscopic examination (mydriasis)- dilate pupil to view retina - Measurements of refractive errors (cycloplegia- paralyze lens) GI: - Irritable bowel syndrome (when diarrhea is the prevelant symptom (IBS-D)) - Treatment of diarrhea - Treatment of sialorrhea - Motion sickness prevention and treatment (scopolamine) Urinary system: - Urge incontinence (to reduce urinary frequency) Respiratory system: - Preoperative use (to decrease bronchial secretions) - Bronchial asthma and chronic obstructive pulmonary disease ** good for asthma and COPD Cardiovascular system: - Treat sinus or nodal bradycardia (due to myocardial infarction or hyperactive carotid sinus reflex) - Treat AV block (due to increased vagal tone) - Cardiopulmonary resuscitation (when vagal hyperactivity is the cause of cardiac arrest)---> the clinical use is no longer recommeded by the American Heart Association Central Nervous system: - Parkinsons disease (Benztropine) Other uses: - To counteract the parasympathomimetic effects of neostigmine in myasthenic pts - Adjuvant use with acetylcholinesterase inhibitors to decrease adverse effects during reversal of neuromuscular blockade - Antidote to poisoning by acteylocholinesterase inhibitors or by certain mushrooms containing muscarine - To decrease sweating (glycopyrrolate applied topically or given IM) - To decrease rhinorrhea (ipratropium by nasal spray)

What are the 3 bacterial mating types involved in conjugation?

F- (females/recipient) or F+ (males/donor)(free plasmid or Hfr (high frequency recombination cell) - F plasmid stably crossed into the chromosome= episome An HFR strain can transfer chromosomal DNA very efficiently (transfer begins at the break in oriT) NOTE: Usually transfer of this large gemone/plasmid breaks off; recipient does not become Hfr or F+ bc usually not all tra genes are transferred (other end of episome) - Homologous recombination stabilizes the new genes For a typical F+ cell containing an F plasmid: 1. F plasmid integrates into chromosome by recombination 2. HFr cells join an F- cell via a conjugation pilus 3. Part of the F plasmid partially moves into recipient cell trailing a strand of donors DNA 4. Conjugation ends with pieces of F plasmid and donor DNA in recipient cell; cells synthesize complementary DNA strands 5. Donor DNA and recipient DNA recombine, making a recombinant F-cell (F minus) NOTE: Conjugative transfer of bacterial genes includes - Hfr mating type - F' plasmid - Integration of genes onto F plasmid by another process (usually transposition) Strains permissive for conjugation: - have receptor for the specific F pilus - can replicate the origin of the plasmid - have compatible restriction/modification systems Some conjugative plasmids can mediate transfer to many differnt species: BROAD HOST RANGE or promiscuous - related to a strong degree - some streptococcal plasmids can be transferred to Lactococcus spp., Lactobacillus spp., Enterococcus spp., Staphylococcus spp., Listeria spp., Pedicoccus spp. - even some in eukaryotic cells Some are very specific, NARROW host range

If the volume of distribution of a drug is provided, the distribution pattern of a drug can be appreciated. Give examples

First off Total Body water= 40L, 60% body weight (this is split into intracellular fluid and ECF) Intracellular fluid= 25L, 40% body weight ECF= 15L, 20% body weight (this is split into interstitial fluid volume= 12L,80% of ECF, and Plasma volume= 3L, 20% of ECF) Examples: a. if a drug has Vd of 2-3L, it can be assumed that it is confined to plasma b. if a drug has a Vd of 13L, it can be assumed that the drug is distributed in the ECF but does NOT penetrate the cells c. If drug has Vd of 40L, it can pass MOST biological barriers and it is distributed in total body water (extra and intracellularly) d. If the drug has a Vd >50L, the drug is likely stored within specific cells or tissues ** If the drug is unable to cross the phospholipid membrane, it will remain in the ECF Features of drugs that predominate in each fluid comparment: Plasma: high MW, bound to plasma albumin Interstitial fluid: low MW, hydrophilic Intracellular fluid: low MW, hydrophobic

How are free radicals related to cell injury?

Free radicals: chemical species with a single unpaired electron in an outer orbital - Reactive oxygen species (ROS): oxygen-derived free radicals Physiological fx.: contribute to aerobic respiration and inflammation Sources of free radicals: - Redox reactions in mitochondria --> O2-. (superoxide radical or superoxide) and OH. - Transition metals: iron and copper (fenton rx: Fe2+ + H2O2--> Fe3+ + OH- + OH. - Inflammatory reactions: generation of NO. (NO. + O2-. = ONOO- (peroxynitrite) - Water radiolysis: generation of OH. + H+ - Enzymatic metabolism of drugs and chemicals, ex. acetaminophen and CCl4 Role of ROS as detoxifying enzymes: - Superoxide dismutase (SOD): 2O2-. + 2H+ --> 2H2O2 + O2 - Catalase (in peroxisomes): 2H2O2 --> O2 + 2H2O - Glutathione peroxidase (in mitochondria and cytosol): (H2O2 + 2 GSH--> 2H2O + GSSG orrrrr 2OH- + 2GSH--> GSSG + 2H2O) Role of ROS, scavengers: - Vitamin E (alpha-tocopherol): terminal electron acceptor (blocks free-radical chain reaction)- lipid soluble: protects cytomembrane - Vitamin C (ascorbate): directly inactivates O2.- and OH. (water soluble) - Retinoids: block free-radical chain reactions (lipid soluble) ROS- Induced inury: - Lipid peroxidation of membranes (ROS --> DB breaks in polyunsaturated lipids)--> peroxide production --> autocatalytic chain reaction (propagation) - Protein cross-linking and oxidation--> unfolding and/or misfolding - DNA fragmentation--> single and double-strand breaks, cross-linking

After a gram stain you find the bacteria is gram-negative bacilli with straight rods and is anaerobic- which bacteria may it be

Fusobacterium - thin and pointy

What are two important check points of the cell cycle that are of interest in neoplasia?

G1/S checkpoint: check for DNA Damage - S phase: phase of no return - G1/S function: prevents cell with damaged DNA from entry to S phase (Stop for DNA repair, If repair CAN NOT be completed --> apoptosis) G2/M checkpoint: check for damaged or unduplicated DNA (G2/M checkpoint) - G2/M function: to prevent a cell with damaged DNA from entry to M phase - important in radiation induced DNA damage

Adverse effects of NSAIDs

Gastrointestinal Adverse Effects: - production of prostacyclin (PGI2) inhibits gastric acid secretion, and PGE2 and PGF2alpha stimulate synthesis of protective mucus in both the stomach and small intestine - inhibition of COX-1 reduces the beneficial levels of these prostaglandins, resulting in increased gastric acid secretion, diminished mucus protection, and increased risk for GI bleeding and ulceration ** NSAIDs should be taken with food (or milk) to diminish GI upset Hematological Adverse Effects: - Aspirin inhibits COX-1-mediated formation of TXA2 and reduces platelet aggregation for the lifetime of the platelet (3-7days) - Platelet aggregation is the first step in thrombus formation, and the antiplatelet effect of aspirin (and other NSAIDs) results in prolonged bleeding time *** Clinical application: aspirin is often withheld for at least 1 week prior to surgery Renal Adverse Effects: - NSAIDs prevent the synthesis of PGE2 and PGI2- prostaglandins that are responsible for maintaining renal blood flow - Decreased synthesis of prostaglandins can result in: retention of sodium and water, and edema ** Pts with a history of heart failure or kidney disease are at particularly high risk for these renal effects- these effects can also mitigate the beneficial effects of antihypertensive medications - NSAIDs and COX-2 inhibitors block PG synthesis, which is important for maintaining renal blood flow and GFR (PG does afferent arteriole vasodilation, NE does afferent arteriole constriction) - NSAIDs block the vasodilatory effect of prostaglandins on the afferent arteriole and reduce glomerular filtration rate Cardiovascular Adverse Effects: - Agents such as aspirin, with a very high degree of COX-1 selectivity at low doses, have a cardiovascular protective effect thought to be due to a reduction in the production of TXA2 - Agents with higher relative COX-2 selectivity have been associated with an increased risk for cardiovascular events (myocardial infarction and stroke), possibly by decreasing PGI2 production mediated by COX-2 (inhibition of endothelial COX-2 derived prostacyclin (PGI2) but not platelet COX-1 derived thromboxane 2 (TXA2) ***ALL NSAIDS carry a BLACK BOX warning regarding the increased risk for cardiovascular events***

Pathology can be split into

General pathology and Systemic pathology General: - Adaptation, Cell injury and death, and accumulations - Inflammation and Repair - Neoplasia - Immunopathology - Hemodynamic Disorders Systemic: - Cardiovascular - Pulmonary - Renal - Endocrine - Reproductive - Etc.

Blood agar (BAP)

General purpose and DIFFERENTIAL medium used to isolate a variety of microorganisms - Usually made with sheep blood - Provides many growth factors for fastidious organisms - Pattern of hemolysis (alpha, beta, gamma) can aid in identification

Generalized vs. Specialized transduction

Generalized: - lytic lifecycle - fragment of host DNA accidentally packaged in phage instead of phage DNA - when the phage injects the bacterial DNA into a new host, bacterial genes are transferred- homologous recombination - phage DNA not present, so recipient cell is transduced, but not infected Specialized: 1. prophage exists in host containing the adjacent gal gene 2. phage genome excises, carrying with it the adjacent gal gene from host 3. phage matures, cell lyses, releasing phage carrying gal gene 4. phage infects a cell that has no gal gene 5. along with the prophage, the bacterial gal gene integrates into the new hosts DNA 6. lysogenic cell contains gal gene In summary: Generalized transduction: - lytic cycle: phage head packages random host (bacterial) DNA fragment ('general') - DNA must be integrated by homologous recombination--> LOW RATE OF SUCCESS (depending on sequence) Specialized transduction: - lysogenic cycle: when phage excises, it brings flanking host DNA with it (specific genes= 'specialized') - phage + host genes integrated by phage recombinases and homologous recombination--> HIGH RATE OF SUCCESS

Adverse Effects of NSAIDs

Generally quite similar for all of the NSAIDs 1. CNS: headaches, tinnitus, dizziness 2. Cardiovascular: fluid retention, HTN, edema, MI and CHF 3. GI: Abd pain, dyspepsia, nause, vomiting, and in some instances ulcers or bleeding 4. Prolonged bleeding time 5. Hepatic: Abnormal liver function test results and rare liver failure 6. Pulmonary: Asthma (inhibition of prostaglandin synthesis cause cause a shift toward leukotriene production) 7. Skin: rashes, all types, pruritis 8. Renal: renal insufficiency, acute renal failure

Intramuscular (IM)

Generally used to acheive systemic effects Absorption: - depends on drug diluents: - aqueous solution- prompt - depot preparations- slow and sustained (depot prepation allows for slow release of a medication over time- this allows for less freq. dosing) Advantages: - suitable if drug volume is moderate - suitable for oily vehicles and certain irritating substances Disadvantages: - affects certain lab tests (creatine kinase) - can be painful

Subcutaneous (SC)

Generally used to achieve systemic effects Absorption: - depends on drug diluents - aqueous solution- prompt - depot preparation- slow and sustained Advantages: - suitable for slow-release drugs - ideal for some poorly soluble suspensions Disadvantages: - pain if drug is irritating - unsuitable for drugs administered in large volumes

What are some factors affecting drug metabolism?

Genetics: - genetic polymorphisms in both phase I and II drug metabolizing enzymes exist that result in altered efficacy of drug therapy or adverse drug reaction Diet & Environment: - Cigarette smokers and workers exposed to pesticides- there is induction of drug metabolizing enzymes more rapidly than with non-smokers & the general population (Ex. Polycyclic hydrocarbons in tobacco smoke that increase theophyllin clearance which may induce CYP1A2) - Grapefruit juice inhibits the CYP3A4 metabolism of co-administered drugs Age: - Infants with immature livers that reduce the rate of metabolism, elderly pts experience a decline in liver size, blood flow, and enzyme production that also slows metabolism Drug-drug interactions (induction and inhibition) Diseases: - Hepatic, cardiac, endocrine and pulmonary diseases can impair drug metabolism Ex: acute or chronic diseases that affect liver architecture or function markedly affect hepatic metabolism of some drugs. heart disease may limit blood flow to the area, affecting drugs whose metabolism is dependent on blood flow

Which RNA genomes are segmented, which are ambisense?

Genomes encode components required for viral replication- could be structural proteins or enzymes, RNAs Some RNA genomes are segments (Reoviridae, Orthomyxoviridae, Arenaviridae, Bunyaviridae) - can be important to epidemiology (ex. flu pandemics) Some RNA genomes are ambisense (Arenaviridae & Bunyaviridae)

p16/INK4A inactivation can be either a

Germline mutation in --> familial melanoma Acquired mutation (deletion or inactivation)--> Pancreatic carcinoma (very common/poor prognosis)

Contraindications of Antimuscarinic Drugs

Glaucoma-- relaxation of ciliary muscle narros the Schlemms canal Prostatic hyperplasia & urinary tract obstruction-- relaxation of detrusor muscle can worsen micturation difficulty *** NOT absolutely contraindicated for BPH- it CAN be used IF in combination with alpha-1 antagonist (ex. Tamsulosin) - need alpha1 blocker to release neck of bladder to release urine GI tract obstruction, Adynamic ileua, Ulceratic colitis, Chronis disease-- the decreased peristalis can cause toxic megacolon Gastric ulcer-- decreased gastric empyting can worsen the ulcer Severe infectious diarrhea- decreased peristaliss can favor the spread of infection Reflux esophagitis-- relaxation of lower esophageal sphincter favors gastric reflux Tachyarrhytmias, Coronary artery disease, cardiac failure, hyperthyroidism-- increased AV conduction can worsen the disease Childrean & elderly: these ages are very sensitive to parasympathetic blockade

What are the gross motor achievements in the bbys first yr?

Goal= walking - 2 months: left head 45* - 4 months: roll over: first front to back, then back to front (easier if you can push off with hands) - 6 months: sit at six - 9 months: crawl, stand (halfway between siting and goal) - 12 motnhs: walk (the goal)

Lipofuscin

Golden-brown, granular, intracytoplasmic material Content: phospholipids, proteins Mechnism: an end-product of free radical injury; derived from lipid peroxidation of polyunsaturated lipids of subcellular membranes Etiology: - Aging ("wear and tear" pigment) - Atrophy - Severe malnutrition Ex: In Myocardium and Liver

In a gram stain, bacteria can either stain

Gram positive --> either cocci or rods Gram negative --> either cocci or rods Stain Poorly: can be - obligate intracellular - spirochetes - mycoplasmma (mollicutes) - acid-fast (mycobacteria)

Enterobacteriaceae are all

Gram-negative bacilli, Facultative anaerobes and Oxidase (-) Found in: - Normal GI flora - Ferment glucose - grow rapidly on non-selective media - lactose utilization is the best start to identifying gram (-) oxidase (-) facultative rods - multiple tests required to get down to genus (indole, citrate, MR-VP, lysine decarboxylase, motility, urease, H2S) Can be Lactose Fermenting ("CEEK") or Non-Lactose-Fermenting ("SYPS") Citrobacter Escherichia Enterobacter Klebsiella Shigella Yersina Proteus Salmonella *Serratia: can be lac (+ or -) , but colonies produce red pigment- many other genera but of lesser clinical importance

All states have a reportable disease list specific to that staet and it may change over time- responsibility of reporting a disease falls on the shoulders of the

HEALTH PROVIDER and NOT the pt typically need to identify how a case compares with case definition- is presentation clinically compatible, suspected, probable or confirmed 2020 Protocol: each condition is categorised by notification timelines and details about what cases require notification (ex. confirmed cases, probable cases, suspected cases, all cases prior to classification) Immediately notifiable, extremely urgent: - call CDC emergency operations center (EOC) at 770.488.7100 within 4 hrs of identification, followed by submission of an electronic case notification to CDC by next business day (Ex. Anthrax (unknown source), botulism, plague, small pox) Immediately notifiable, urgent: - Call CDC EOC within 24 hrs, followed by submission of an electronic case notification in next regularly scheduled electronic transmission (ex. measles, rabies) Routinely notifiable: - submit electronis case notification within the next reporting cycle (ex. HIV, Lyme disease, cryptosporidosis) ---- Why report? Statistical analysis: - prevalence, incidence - trends, track outbreak - establish treatment guidelines Control future outbreaks: - establish contact lists - educate possible contacts on disease - encourage contacts to get tested

Human Papilloma Virus (HPV)

HPV type 1,2,4, and 7 --> skin warts HPV type 6 and 11--> anogenital warts and mild cervical dysplasia (virus exists in episomal form) HPV type 16,18, 31***** and - viral integration into the host genome with elaboration of E6 and E7 oncoproteins---> moderate-to-severe cervical dysplasia (including Ca in situ) and invasive squamous cell carcinoma **HPV E6--> inhibits p53 **HPVE7--> inhibits RB-E2F

Trypanosoma and Leishmania are

Haemoflagellates "blood flagellates" - Insect-borne flagellates found in blood, tissue, lymph, and CSF These exsist in 4 forms: - Amastigote (in human tissue) - Promastigote - Epimastigote - Trypomastigote (in human blood plasma)- ** be able to identify in blood plasma **NOTE when you see amastigote and trypomastigote these are diagnostic for Trypanosoma and Leishmania Trypanosomas: I. African tryponosomiasis (sleeping sickness- CNS demyelination--> become sleepy) - Trypanosoma gambiense - Trypanosoma rhodesiense II. American trypanosomiasis (Chaga's disease) - caused by Trypanosoma cruzi Leishmania: - Leishmania tropica - Leishmania brasiliensis - Leishmania donovanii Trypanosoma Vectors: T. gambiense (from the tsetse fly, West Africa) T. rhodesiense (from tsetse fly, East Africa) T. cruzi (from the reduviid bug, Americas)

After a gram-stain you find that the bacteria is a gram-negative bacilli, coccobacilli/pleomorphs (most non-motile) and a facultative anaerobe- what bacteria could it be

Haemophilus or Pasteurella Haemophilus: - often seen as a rod, can grow as long filaments - requires factor X (heme) and factor V (NAD) - chocolate agar (CAP) - oxidase (+/-) Pasteurella - can display bi-polar staining - blood or chocolate - oxidase (+)

Candida spp.- Candida Albicans

Has 3 forms: pure yeast, pure hyphae, mutated pseudohyphae - Genus is generally regarded as a yeast. Most Candida species are part of our normal flora (mainly mucosal but also in moist cutaneous areas) - Most species including the most important Candida albicans, form pseudohyphae when they invade tissues (so almost the reverse of the thermally dimorphic fungal pathogens) - Candida albicans and C. tropicalis form TRUE hyphae when they cause infection NOTE: Germ tube is the structure when its deciding to become a hyphae but then it forgets and forms a pseudohyphae ***Overgrowths or invaded tissues of Candida Albicans have pseudohyphae and true hyphae as well as yeasts In summary: C. albicans can form yeast, pseudo-hyphae, germ tubes & true hyphae (it is polymorphic) ** Drug resistance is a problem in several Candida specia (most commonly non-albicans species)--- Ex. Candida with diff name at the end other than albicans usually signifies drug resistance NOTE: Most species of Candida albicans are part of our normal flora (mainly mucosal but also in moist cutaneous areas) - wet mount to diagnose yeast vaginitis, diaper rash, etc.

Pharmacokinetics of Aspirin (aka acetylsalicylic acid, ASA)

Has a pKa of 3.5 - After oral administration, aspirin is rapidly hydrolyzed to acetic acid and salicylate by esterases in the body - Unionized salicylates are passively absorbed mainly from the upper small intestine; salicylates can also cross both the blood-brain barrier and the placenta and are absorbed through intact skin (especially methyl salicylate*** which is in drug list it manages mild msk pain) Salicylate is converted by liver to water-soluble conjugates that are rapidly cleared by the kidney, resulting in first-order elimination and serum half-life of 3.5hrs - At anti-inflammatory dosages of aspirin (more than 4g/day), the hepatic metabolic pathway becomes saturated, and zero-order kinetics are observed, leading to a half-life of 15 hrs or more What happens if a pt overdoses on aspirin? - zero order kinetics- saturation and accumulation--> toxicity is possible Salicylate is secreted into the urine and can affect uric acid excretion- what is the implication of this? Gout, increased uric acid - Aspirin is available as an enteric coated tablet which provides GI protection but delays the onset action of the drug

Chlamydiaceae

Have an outer membrane with LPS but NO PG (instead have a cys-rich envelope of proteins - Unrelated to gram negative bacteria - Usually unreactive in gram stain (intracellular (difficult to grow in lab bc need to grow in other cells), cell wall structure) ** Genera of importance: Chlamydia, Chlamydophila

Differentiate between Heat and Chemical Sterilization

Heat Sterilization: - Autoclave or oven - Steam: 121*C, 15 psi, 15 min (can get water higher than 100*- you can boil bacteria and it wont die) - Dry heat (must go hotter for longer to achieve sterilization)--> 170*C, 60min (standard) Chemical sterilization: Ethylene oxide (EO or EtO) - Gaseous sterilants penetrate very well - Most common - Very effective, but long, dangerous and toxis Plasma (hydrogen peroxide) gas: - H2O2 gas is treated with EM--> free radicals - end up with oxygen and water (non-toxic) Formaldehyde, glutaraldehyde: - Irritant, smelly, carcinogenic (downside) Peracetic acid

Why is the study of microbial pathogens important?

Helps us to identify certain disease or injury as causes of death amongst a group of people Ex: Lower respiratory infections are responsible for 4.2 deaths of upper income people and 7.1 percent of deaths in the world in 2004 What makes the difference? Sanitation (infrastructure) - prevents exposure - biggest impact* - prevents illnesses transmitted by WATER, food, direct contact Vaccination - prevents infection in exposed - significant impact - limited by R&D, biology Antibiotics - cure infections - significant impact - losing effectiveness

Describe Bone Marrow suppression as a virulence mechanism of viruses

Hematopoietic cell death due to: - infection and death of hematopoietic stem cells - CD8 secretion of IFN-gamma and TNF-alpha - excess inflammation (Type I and Type II IFNs, as well as TNF-alpha) Direct effects: 1. Viral infection: suppresses HSPC differentiation and sruvival 2. Viral recognition: enhances HSPC proliferation, differentiation and homing Indirect effects: 3. Infalmmatory mediators: Diverses effects on HSPC self-renewal, proliferation and differentiation 4. BM micro-environment: controls HSPC proliferation and differentiation

List the partially dsDNA (circular) viruses

Hepadnaviridae (enveloped) * this is DNA

Differentiate between the vaccine given for Hepatitis B and A

Hepatitis B - Subunit (HBs surface glycoprotein), adjuv. - Should be given to children, healthcare workers, high-risk groups (i.e. injectable drug abusers) Hepatitis A - Inactivated, adjuv. - Should be given to children, child care workers, travelers to endemic areas, Native Americans, and Alaskans

alpha-fetoprotein (AFP) is a marker for

Hepatocellular carcinoma and yolk sac tumors

Aflatoxin B1 (an indirect initiator)

Heterocyclic hydrocardon, metabolized to epoxide, covalently binds DNA Produced by fungus Aspergillus flavus that thrives on improperly stored grains and peanuts Induced cancer: hepatocellular carcinoma in Africa and Far East Mechanism: TP53 inactivation - G:C--> T:A transversion at codon 249

Mannitol-salt agar (MSA)

High salt concentration inhibits all but osmotolerant organisms - fermentation of mannitol results in acid production, causing a drop in pH and turning pH indicator from red to yellow. - usefull in selecting for staphylococci (haloduric= osmotolerant)= salt-tolerant, and differentiating S. aureus (ferments mannitol) from coagulase-negative staph (do not ferment mannitol)

Differentiate between High, Intermediate and Low level disinfectants

High-level: - Kills/inactivates ALL but high spore loads - Bleach (hypochlorite), low levels of chemical sterilants or less heat - Aldehydrs, O2-based, some halogens often fall into this category Intermediate-level: - Idophors, alcohols, phenolics - Will kill vegetative bacteria, some viruses, some fungi, a few can kill mycobacteria (but high is better for these) Low-level: - Quaternary ammonium compounds, triclosan (may be in some toothpastes) - Will kill vegetative bacteria, some viruses (enveloped or larger-size) and some fungi

Local or general spread (dissemination) of bacteria- can be due to host and bacterial factors

Host factors that contribute to dissemination: - movements of fluids (secretions, blood, lymph etc.) - cellular trafficking - localized inflammation that causes damage Bacterial factors that contribute to dissemination: - Motility: swimming, swarming, twitching - Localized production of enzymes (toxins, proteases, dnases)

What are 2 mechanisms used by bacteria in hiding from the Host Immune System?

Host mimicry & Anitgenic variation Host mimicry: - Microbial surface structure is antigenically similar to a host structure - If structures is abundant, host has difficulty mounting an effective immune response against the pathogen Antigenic Variation: - Genetic mechanisms cause changes in certain microbial surface antigens - Acquired response no longer recognizes pathogen - (Phase variation: structure present/absent)

Paraneoplastic Syndromes, Ectopic Hormone Production

Hypercalcemia- cause: PTH-related peptide production - seen in Squamous cell lung carcinoma, Renal cell carcinoma, breast carcinoma Syndrome of inappropriate antidiuretic hormone secretion (SIADH) - seen in Small Cell lung carcinoma Cushing syndrome (cause- ACTH production) - seen in Small cell lung carcinoma Polycytemia - seen in Renal cell carcinoma Acantosis nigricans (grey-black veruccous hyperkeratossis in the axillary and groin areas) - seen in gastric carcinoma, bronchogenic carcinoma, uterine carcinoma Disseminated intravascular coagulation (DIC) - seen in acute promyelocytic leukemia - prostatic carcinoma Coagulopathy (nonbacterial thrombotic endocarditis and migrating thrombophlebitis (Trousseau Syndrome) - Seen in advance mucin-producing tumors: pancreatic carcinoma & bronchogenic carcinoma Lambert-Eaton syndrome: - seen in Small cell lung carcinoma Hypertrophic osteoarthropathy (finger and toe clubbing) - seen in Bronchogenic carcinoma

Differentiate between pathologic hyperplasia vs. neoplasia

Hyperplasia - responds to normal regulatory CONTROL mechanisms (controlled proliferation) - reversible, i.e., resolves after the stimulus stops acting Neoplasia - Does NOT respond to regulatory mechanisms - NON-reversible

SAFE

IPV/DV screening Stress/Safety: - What stresses do you exp in relationship? - do you feel safe? Afraid/abused: - what happens when u disagree with partner? - have you felt afraid? - have you been phys hurt/threatened - been forced to engage in sex? Freinds/fam - do friends/fam know? Emergency: - safe place to go in emergency? ------- As a physician - offer support (empathy, validation, assistance) - help them move through stages of change--- pre contemp (not concerned about sit), contemp (considering but not ready), action (actively seeking help and taking steps to address situation) - encourage and facilitate using resources -- national help hotline: 1800799SAFE , developing safety plan, prepare emergency kit & Document - history, PE, photographs - preserve physical evidence - record suspicions Difficulties phys may encounter: - powerlessness with time constraints - privarcy with safety concerns - lack of training with phys bias - fear of offending pt with culture

What are some ways that drugs may be given intravenously?

IV bolus multiple dose: a single dose is given at repeated intervals (ex. 100 mg IV every 8 hrs) Multiple Intermittent infusions: a dose is given over short time at repeated intervals (ex. 100 mg infused over 30 minutes every 8 hrs) Continuous infusions: a drug is given over an extended time (ex. 100 mg infused over 8 hrs) NOTE: many drugs are better tolerated when infused slowly over time compared to IV bolus dosing **Drug administration by the IV bolus miltiple dose and the intermittent infusion methods may result in fluctuations in plasma concentration over time (peaks and troughs) **Continuous IV infusions allow for the maintenance of a consistent plasma concentration over the time

WNT Signaling Pathway

In resting cell: - APC (Adenomatous Polyposis Coli) initiates proteosomal degradation of Beta-catetin Activation of WNT receptor: - Prevents degradation of Beta-catetin-> Beta-catetin enters the nucleus and forms a transcription activating complex with TCF (T-cell factor) Loss-of-function mutation in APC gene prevents degradation of Beta-catenin --> Inherited or Sporadic type Inherited vs. Sporadic Mutation of APC: Inherited loss-of-function mutation in APC gene: - FAP (familial adenomatous polyposis) - hundreds/thousands of adenomatous polyps in the colon - some polyps invariable progress to carcinoma Sporadic mutation of both APC alleles - Sporadic colon carcinoma - Hepatoblastoma and hepatocellular carcinoma

Classifications of Bacterial infections

Inapparent (subclinical): no detectable clinical symptoms of infection - Ex: asymptomic gonorrhea in women and men Opportunistic: Infection caused by normal flora or transient bacteria when normal host defenses are compromised - Ex: Serrati or Candida infection of the genitourinary tract Primary infection: Clinically apparent (ex. invasion and multiplication of microbes in body tissues, causing local tissue injury) - Ex: Shigella dysentery Secondary infection: Microbial invasion subsequent to primary infection - Ex: bacterial pneumonia following viral lung infection Acute Infection: Rapid onset (hours or days); brief duraction (days or weeks) - Ex: Diphtheria Chronic Infection: Prolonged duration (months or years) - Ex: myobacterial diseases (tuberculosis and leprosy) Pyogenic: Pus-forming - Ex: staphyloccai and streptococcal infection

Prenatal Period

Includes: pre-preg, preg, delivery (perinatal) Pre-preg period - preg outcome= influenced by facotrs preceding conceptions - womans general state of health prior to conceiving (substance use, STI, chronic conditions) - social facotrs: support, attitude towards pred, domestic violence *public health measures targeting womens health in childbraring period= optimize well being and decrease neg outcomes in offspring Preg - Factors influencing can be: psychological, socio-economic, nutirtion, metabolic, chronic disease, maternal age, infections, pharmacological, stage of fetal maturation - Epigneetics= change in phenotype without change in genotype (i.e. DNA methylaiton, Histone modification, non-coding RNA associated gene silencing) - multifactorial diseases - teratology (teratogens that interfere with nml in utero develop. --- DNA methylation changes and altered gene expression may be involved Perinatal period (delivery) - gestational age: preterm, term, postdates - complications: placenta praevia, accreta - babies large for gestational age are at risk of birth injuries (ex. brachial plexus injury)

Adjuvants that enhance immune response

Incomplete Freunds adjuvant (oil-in-water emulsion) - MOA: delayed release of antigen; enhanced uptake by macrophages Complete Freunds adjuvant (oil-in-water emulsion with dead mycobacteria) - MOA: delayed release of antigen; enhanved uptake by macrophages; induction of co-stimulators in macrophages Freunds adjuvant with MDP (oil-in-water emulsion with muramyldipeptide (MDP), a constituent of mycobacteria) - MOA: similar to complete Freunds adjuvant Alum (aluminum hydroxide) (aluminum hydroxide gel): - MOA: delayed release of antigen; enhanced macrophage uptake Alum plis Bordetella pertussis (Aluminum hydroxide gel with killed B. pertussis) - MOA: delayed release of antigen; enhanced uptake by macrophages; induction of co-stimulators Immune stimulatory complexes (ISCOMs) (Matrix of Quil A containing viral proteins) - MOA: dlivers antigen to cytosol; allows induction of cytotoxic T cells

Describe Antibody detection in Microbial identification

Indirect way of inferring presence of organism or microbial product, by looking for pathogen-specific host antibodies Used in particular cases: - when pathogen is dangerous, difficult to grow, inaccessible or in low numbers - to track course of illness (acute to convalescent) - to determine immune status and disease status Commonly used for diagnosis and management of numerous infections: - Viruses (CMV, VZV, Hepatitis Viruses, Influenze and more) - Intracellular or difficult to grow bacteria (Treponema pallidum, Leptospira, Chlamydia, Rickettsia, and many more) - Fungi (Histoplasma, Coccidioides, Blastomyces, Candida)

Hepatitis B and C Viruses (HBV and HCV)

Induced tumor: hepaocellular carcinoma Geography: - HBV: Far east and Africa - HCV: North America and Europe Carcinogenicity: neither HBV, nor HCV possess oncoproteins Mechanism: Chronic inflammation--> persistent regeneration--> hyperplasia

DIfferentiate between inducers and inhibitors of CYP 450

Induction: - results in accelerated substrate metabolism and usually in a decrease in the pharamcologic action - in case of drugs metabolically transformed to reactive metabolites, enzyme induction may exacerbate metabolite-mediated toxicity - some drugs can induce their own metabolism - Ex: prodrugs go quickly into their active form via induction Inhibition: - Significant increases in plasma drug concentration and resultant adverse effects or drug toxicity (toxic/adverse reaction) ** A Prodrug needs to be metabolized to pharamcologically active drug- if metabolism of a prodrug is induced--> drug will be rapidly convereted into the active drug - if prodrug is inhibited the drug will NOT be converted into the active drug (or the conversion will occur very slowly) Ex: Clopidogral is an antiplatelet drug, it is a produce - CYP2C19 isozyme is mainly responsible for the bioactivation of clopidogrel - Concurrent use of clopidogrel and drugs that inhibit CYP2C19 could inhibit conversion of clopidogral to its active form - A proton pump inhibitor, omeprazole, is one of the inhibitors of CYP2C19. - Before this interaction was widely known, proton pump inhibitors (ex. omeprazole) were prescribed with clopidogrel to prevent gastrointestinal bleeding **FDA-approved labeling now recommends avoiding concurrent use of the PPIs (ex. omeprazole) with clopidogrel - Concurrent use of clopidogrel and proton pump inhibitor (PPI) may result in decreased levels of the clopidogrel active metabolite and ultimately its antiplatelet activity

Language Development

Infancy: - newborn: respons to human voice - 2 months: gooing - 3: elongate vowels- oo , aaa - 4-5: imitates tones - 6: canonical babling stage - 8: variegated babbling stage - 9-10: conversational babbling, jargon stage - 12: speak one or more words Toddler: - 1-2: new words, body parts, simple commands and questions, two words, simple stories, points to pictures when named in books -2-3: two-3word phrases, is understood, names objects, able to direct attention Pre-school: - 3-4yr: answers who, what , where and why?, talks about activities, uses 4 or more words - 4-5yr: pays attnetion to short story, tells storys, adult grammar, rhyming words, letters and numbers School age: - speech is fluent and child is able to express ideas

Transduction

Infection by a nonlethal virus carrying bacterial genes Process: 1. Transducing phage containing donor genomic DNA 2. Cell lysis; release of phages 3. Phage infects recipient cell; donor DNA integrates into recipient DNA Phage terminology: - Lytic: phage that causes killin of host bacterium - Lysogenic: phage that can survive in the bacterium without killing- usually integrated in the bacterial chromosome - Temperate: phage capable of undergoing both lytic or lysogenic development - Virulent: phage capable of undergoing ONLY lytic development - Lysogen: bacterium harboring a lysogenic phage - Prophage: integrated phage genome in a bacterium (lysogen) Ex: of DNA transfer mediated by bacteriophages - E.coly + lambda phage (it erupts bc it has high concentration of lambda phage in it) NOTE: there is both Generalized and Specialized transduction- know the difference!

CDC Nationally Notifiable Conditions

Infectious Diseases, Non-infectious Conditions, Outbreaks >/= 2 cases after where food or water exposure is implicated as cause of illness Reportable vs. Notifiable Conditions Reportable- MANDATORY - heath provider, hospital or laboratory - MUST notify state - uses personal identifiers - enables state to identify where immediate disease control and prevention is needed Notifiable- VOLUNTARY - To CDC from state and local - does NOT include personal identifiers - Nationwide aggregation of data - Monitoring of disease - helps formulate prevention plans - regular, frequent and timely reporting aids with identification of populations and geographic regions at risk ** Laws and regulations vary sig. by state!

Complications during delivery

Injuries and/or birth asphyzia (complicated delivery) Cerebral palsy: UMN injury from birth asphyxia -- decreased interavtion with environemnt: - decreased attahcment - secondary developmental delay APGAR score: reflects need for resuscitation - Done at 1 and 5 minutes - Normal score= 8-10 - score of 0 does NOT indicate death as new born may be in primary asphyxia A- Appearance (normal: 2, acrocyanosis:1, generalized cyanosis: 0) P- Pulse (normal>100BPM: 2, bradycardia <100BPM:1 , absent:0) G- Grimace (crying:2, faint crying and grimacing:1, no response:0) A- Activity (fully flexed on stimulation: 2, some flexion: 1, flaccid: 0) R- Respirations (vigorous cry: 2, bradypnea with weak cry: 1, apnea: 0) Maternal support in labor enhances outcome - allow father to be as involved as possibl - support from "doula" sig decreases need for instrumental deliveries

How are herpesvirus contained by immunity?

Innate: - Antiviral state [Type I (IFNalpha/IFNbeta) & Type III (IFN-gamma) - NK cells - gammadelta T lymphocytes (IELs) - activated macrophages Adpative: Th1 mostly Cellular: - cytotoxic T lymphocytes Humoral: - IgG (antibody-dependent cell cytotoxicity) - IgA bc mucosa Immunosubversion by Virus: - Interfering with antigen presentation - Interfering with complement and immunoglobulin - Interfering with cytokine signaling, gene transcription and apoptosis Ex of Interference with antigen presentation: - occlusion of TAP1/TAP2 channel by viral protein ICP47 Ex of interfernece with IgG: neutralization of neutralizing antibodies by viral glycoproteins gE-gI Ex of interfernece with PKR-induced apoptosis - Us11- enable virus to counteract host intrinsic viral system

Innate Immune Defenses

Intraepithelial T lymphocytes (IELs): - "Sort of hybrids between cytotoxic T lymphocytes and NK cells" - Kill infected cells with no prior activation requirement Steps: - Virus infects mucosal epithelium cell - Infected cell displays viral peptide to CD8 IEL via MHC class I - Activated IEL kills infected epithelial cell by perforin/granzyme and Fas-dependent pathways - Epithelial cells undergo stress as a result of infection, damage, or toxic peptides, and express MIC-A and MIC-B - NKG2D on IELs binds to MIC-A, B and activate the IEL- CD8alpha:alpha homodimers also bind to TL - Activated IEL kills the stressed cell via the perforin/granzyme pathway

Describe invasive Candida infections

Invasion through enzymes which damage tissues: proteases, elastases - Invasion through IV lines or urinary catheters ** Hyphae filament usually burrows down into skin ** Untreated surface overgrowth can lead to invasive infections: Ex. thrush, diaper rash

Urinary Incontinence

Involuntary leakage of urine 2 types: 1. Urge urinary incontinence: urine leakage accompanied by urgency. Sometimes referred to as overactive bladder (Detrusor overactivity) ** relax it with beta3 stimulation or block M3 to relax the Detrusor muscle 2. Overflow incontinence: Occurs mainly in men secondary to prostatic enlargement. Overflow incontinence is the involuntary loss of urine associated with bladder over-distension (Detrusor underactivity) ** Stimulate with M3 or block Beta3

Passive immunization

Involves injection of purified antibodies or antibody-containing serum Provides rapid, temporary immunity to exposed individual - Rapid: anitbodies are immediately available to protect against infectious agent or its products - Temporary: decreases as immunoglobulins are cleared from the recipients serum over a few weeks to months Types of Passive Immunization: A. Non-specific standard immunoglobulin - obtained from plasma donors - contains serum proteins & immunoglobulins (predominantly IgG, range of specificities to various Ags arising from both natural immunity and from immunization) B. Hyperimmune human immunoglobulin - contains high conc. of antibodies specific for a particular pathogen or toxin - administered to pts expose to a particular agent Immune globulins are available for post-exposure prophylaxis for: - Hepatitis A and B - Measles - Rabies (+) - Chickenpox, varicella-zoster (+) - Cytomegalovirus - Rh (Rho(D) or RhiG) - Tetanus (+)- human and equine - Botulsm (+)- human and equine - Diphtheria- equine - A variety of animal venoms (antivenoms)- equine, ovine & others (+)= specific high-titer antibodie (hyperimmune Ig) is available and is the preferred therapy

Ionizing Radiation

Ionizing radition, types: - Electromagnetic radiation: x and gamm rays - Particulate radiation: alpha- and beta-particles, and high-energy neutrons Use in medicine: - Treatment of cancer - Diagnostic imaging Units of Ionizing radition: - Amount of radiation emitted by a sources: Curie (Ci) - Amount of energy absorbed by the tissue: Gray (Gy) - Biological effects of a particular type of radiation for a given amount of absorbed energy (equivalent dose): Sievert (Sv) Cellular & Tissue Effects: - Nuclear changes: apoptosis and necrosis - Cytoplasmic changes: cytoplasmic swelling, degeneration of mitochondria and ER Vascular changes: - Early: endothelial swelling and necrosis of vascular wall - Later: endothelial proliferation, sub-intimal fibrosis, hyalinization, and lumen obstruction( lumen closes bc of proliferation) Fibrosis: with following scarring and contractions Acute Whole Body Radiation Injury= Acute Radiation Syndrome (ARS): Phases depend on the dose and may overlap: - Prodromal phase: apathy, anorexia, nausea, vomiting, diarrhea, fever, headache, etc. - Latent phase - Manifested illness phase: hematopoietic, intestinal, or cerebrovascular subsyndromes - Recovery phase or death ARS Subsyndromes: - Hematopoietic (Neutropenia and thrombocytopenia)- 2-5Gy --- ~50% survival rate, depense on dose - Intestinal (Abd pain, diarrhea, bleeding, perforation)- 5-12Gy--- Death within few weeks - Cerebal (Damage to the BBB, cerebral edema, petechial hemorrhages) >/=20Gy -- Death within a few days

After a gram stain, you find that the bacteria is a gram-negative bacilli- what should be your next investigation?

Is it a Coccobacilli/pleomorphs (most non-motile), curved and spiral rods (motile) or a Striaght rod) THEN If cocobacilli/pleomorphs (most non motile)--> is it an aerobe (non-fermenter) or facultative anerobes- or an anaerobe Aerobes (non-fermenters) can be: - Acinetobacter sp. - Moraxella sp. - Francisella sp. - Brucella sp. - Bordetella sp. Facultative Anaerobes can be: - Haemophilus - Pasteurella Anaerobes can be: - Bacteroides - Prevotella - Porphyromonas If curved and spiral rods (motile)--> is it an aerobe or facultative anaerobe? Aerobes can be: - Campylobacter sp. - Helicobacter sp. Facultative Anaerobe: - Vibrio sp. If straight rods--> Facultative anaerobe, aerobes (non-fermenters), or anaerobe Facultative anaerobe--> Oxidase (-) may be: - Enterobacteriaceae - Serratia Then ask are they lactose-fermenting (CEEK) or Lactose non-fermenting(ShYPS) Lactose fermenting (CEEK): - citrobacter - enterobacter - escherichia - klebsiella Lactose non-fermenting (ShYPS) --> ask are they non-H2S producing or H2S producing? Non-H2S producing: - Shigella - Yerisinia H2S producing: - Proteus - Salmonella Aerobe (non-fermenter)--> Oxidase (+) may be: - Pseudomonas sp. - Legionella sp. Anaerobe: - Fusobacterium

What are some clinical examples of ischemic conditions?

Ischemia is a reduction in blood flow to tissues and it is a cause of hypoxia (a reduction in amount of O2 available to tissues) Examples: - Artherosclerotic occlusion, ex. coronary artery - Low cardiac output, ex. left-sided heart failure or shock - Torsion of vessels, ex. mesenteric or testicular artery - Compression from outside, ex. a tourniquet

Describe the structure and function of periplasm in bacteria

It is a viscous solution of proteins and solutes - between plasma membrane and PG/outer membrane Gram +: have a small periplasmic space (increased PG, teichoic and lipoteichoic acid - periplasmic space needed for various important functions even through some sources say its not present Gram -: have a big space between outer membrane and cytoplasmic membrane (big periplasmic space) Function of Periplasm: - Protection against osmotic lysis via solutes - Biosynthesis (peptidoglycan, fimbriae) - periplasm is where PG gets made - Nutrient binding - Macromolecule degradation - Detoxification - Chemotaxis receptors - No single major function (bc it is a work space for bacteria to move things in and out, process nutrients and signals its receiving from its environment)

What are the functions of peptidoglycan?

It is essential to most bacteria (EXCEPT FOR: mollicutes, Chlamydiaceae, some other intracell.) It protects aginast osmotic lysis (2nd layer of protection from osmotic lysis so this shows its important function) Provides shape - bacteria have diff. shapes bc they live in different environments, they use their shape to their advantage Protects against some chemicals and large molecules - highly polar- some cheimcals cannot pass - pores block passage of large molecules Anchor site of some proteins and polysaccharides to cell (especially ones on the outside of cell as projections need a way to anchor and not snap off the surface) Biological effects of PG: A PAMP (pathogen associated molecular pattern): - unique to bacteria, present/similar in MOST bacteria - induction of IL-1, IL-6, GCSF, TNFalpha Cytotoxin (a specific type of PG fragment in some organisms) - e.g. Bordetella pertussis- tracheal cytotoxin, targets ciliated respiratory epithelial cells (PG can be a toxin- i.e. Bordetella pertussis "whooping cough")

What is the cytochrome P450 family of enzymes important for?

It is important for metabolism of many endogenous compounds and for the biotransformation of exogenous substances - CYP is a superfamily of heme-containing isozymes located in most cells, but primarily in the liver and GI tract - There are more than 50 CYP450 enzymes, but the CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 enzymes metabolize 90% of drugs **** These enzymes are an important target for phamacokinetic induction and inhibition drug interactions

Describe the structure of RNA polymerase

Its core enzyme is made up of 5 subunits (alpha2betabeta'w) - core alone binds DNA, but does NOT recognize promoters efficiently - sigma factor adds specificity and promoter-binding - sigma factor and RNApol together= holoenzyme ** these can be target sites of antibiotics

HHV-8

Kaposi Sarcoma-Associated Herpesvirus - Encodes several proteins that resemble human proteins and promote the growth and prevent apoptosis of infected and surrounding cells --- these proteins include: IL-6 homolog (growth and antiapoptosis), Bcl-2 analog (antiapoptosis), chemokines, and a chemokine receptor These proteins can promote growth and development of polyclonal Kaposi sarcoma cells in AIDs pts and others HHV-8 DNA is present is associated with peripheral blood lymphocytes, most likely B cells, in apprx 10% of immunocompetent ppl - It is more prevalent in certain geographic areas (Italy, Greece, Africa) and in pts with AIDS **Kaposi sarcoma= most ocmmon cancer in sub-Saharan Africa and the virus is most likely sexually transmitted disease but may be spread by other means Herpes simiar (B virs) subfamily of alphaherpesvirinae, the simian counterpart of HSV- is indigenous to Asian monkeys-- transmitted to humens by monkey bite or salive - after infection human may have pain, localized redness, and vesicles at site of entry - encephalopathy develops and is often fatal -- if survive most often have serious brain damage - PCR or serologic tests can be used to establish the diagnosis of B-virus infections- Virus isolation req. special facilities

Beta-nonselective and alpha1-antagonists (Beta1, Beta2, alpha1)

Labetalol Carvedilol

List and describe some types of microscopy used in diagnosis

Light microscopy (brightfield) - Wet mounts (usually larger cell types), perhaps with phase contrast - Stains such as gram, acid-fast, capsule, giemsa - Not valuable from sites with normal microbiota; isolation first Darkfield microscopy (Spirochetes) Fluorescence microscopy: - Autofluorescence: few organisms - Fluorescent stains: Chemical with a direct affinity for a microbial component (Calcofluor white for fungi and Auramine O for mycobacteria) - Immunofluorescence: sensitivity/specificity vs fluorescent stain? How can you use these results? Uses clinical specimen (direct smear) or isolated microbes: - quick way to narrow down causative agent, narrow treatment - directs confirmatory or further tests Particularly helpful with rare morphology or staining property (ex. ova, acid-fast bacteria) and from otherwise sterile sites

A pt with metastatic colon cancer was fund to have lungs that were markedly consolidated and had several cavities 2-4cm in diameter with liquefied material pouring out from the cavities when the lungs were sliced- this is most likely do to

Liquefactive necrosis ** this is seen in abscesses

Growth of bacteria in the laboratory can use

Liquid or Solid media Liquid media: - Easiest to prepare and use - Good for growing quantities of mirobes - Unless inoculated with a pure culture, it cannot separate bacteria Solid media: - Usually made by adding agar, a seaweed extract, to liquid - Agar melts at 80-90 degrees celsius, but when it cools it and acts a inert gelling medium ** this allows for separation of different media out

Disadvantages of Live Vaccines

Live organisms can pose a threat to individuals who cannot effectively resolve even a mild infection (i.e. immunocompromise individuals or pregnant women) - the attenuated virus strain may revert to wild type (virulent form of the virus) - since the organism is living, viability must be maintained

Basic Pharmacokinetic Equations

Loading Dose (LD)= (Css x V)/ F Maintenance dose= (Css x CL X t) / F T1/2= (0.7 x Vd)/ CL CLh= Q x ER (where Q is hepatic blood flow and ER is fraction of drug extracted by the liver) CLr= (urine flow rate x urine drug concentration)/ plasma drug concentration Vd= (Dose x F)/ (Cpo) F= AUCother/ AUCiv

Types of Neoplasm-Host interaction

Local growth, expansive and invasive - Expansive growth: Tumor expands and compresses surround tissue with formation of a fibrous tissue rim (capsule)-- a feature of benign tumors (i.e. breast fribeoadenoma) - Invasive (or infiltrative) growth into surrounding tissues-- a feature of malignant tumors *** Many benign tumors have NO CAPSULE and may mimic invasive growth (ex. Hem- and lymphangioma, and desmoid) Spread of malignant tumors, direct and distant- metastases Recurrence Effects of tumor on the host Anti-neoplastic immune response

Describe reactivation of Alphaherpesvirus from the Latent cycle

Local stimulation: - stimulation of tissues innervated by latently infected nueorns Systemic stimulation: - Physical stress - Emotioal stress - Hyperthermia - Menstruation - Hormonal imbalance Decrease in LAT and microRNAs (deacetylation of histones associated with the LAT gene) Increase in lytic gene expression (acetylation histones associated with lytic genes)

Describe the structure and functions of Capsuls and Slime in bacteria

Long chains of sugars, sugars/amino acids, or amino acids - Sometimes called "glycocalyx" Capsule: - organized, tightly cell-associated - anchored via lipid in membrane or covalently onto PG Functions of capsule: Antiphagocytic- major role - negatively charged for many pathogens - reduction off complement-mediated opsonization May permit host mimicry One species may express many different structures; strain-specific - "K" antigen in some serotyping schemes, numbered in others, letters in others (ex. K1, K5 capsule types in E.coli related to invasive disease - Vaccine target (ex. Pneumococcus, meningococcus) - Can have other roles (adhesion, protection from desiccation) Slime: - disorganized, loosely- associated (no anchor) Functions of Slime: Adhesion to surfaces or cells -> Biofilm formation - Aid in attachment, growth and dispersal ** Some pathogens make HUGE amounts of capsule, looks like slime

MOA of Alpha2 agonists

Low doses: - alpha2-agonists are sympatholytic; they block the symp arm of the ANS --> due to inhibition of firing in the locus ceruleus - Sympatholysis is also due to activation of alpha2-autoreceptors on presynaptic neurons that inhibits the release of NE (lowers BP; mainly CNS) High doses: - alpha2-agonists constrict BV by activating postsynaptic alpha2-receptors (increases BP; mainly peripheral)

Describe the pathophysiology of Orolabial Herpes (Alphaherpesvirinae)

Lytic cycel in Epithelial cells (Lesions: 1. Infection of Epithelial cells 2. Ballooning of cells with condensed, marginated chromatin (Viral replicative cycle) 3. Loss of cell membrane integrity/syncytium formation 4. Multinucleated giant cells 5. Lysis 6. Release of vesicular fluid between epidermis and dermal layer (virus, cellular debris, inflammatory cells, multinucleated giant cells) 7. Inflammatory response which can afffect eithr skin or muscosa - Skin--> pustules w/ inflammatory cells - Mucosa --> shallow ulcers **Direct introduction of microbe into epithelium--> Macule (flat, red) local inflammation immune response infiltrating leukocytes Clinical course: - Incubation--> tender lns --> vesicle--> wet ulcer--> crust--> healthing - sxs: pain, itching, dysuria, malaise, fever - virus shedding-- healing **Latent in DRG (retrograde transport of incoming capsids denuded of tegument proteins) ** Reactivation: Nuclear accumulation of VP16 & HCF-1 supporting IE gene expression leading to production reactivation) anterograde transport of new capsids and virion factors Complications: Mostly in Neonatal and immunocompromised: - Encephalitis (HHV-1/HHV-2) - Disseminated disease (HHV-2) - Hepatitis (HHV-1/HHV-2) - Esophagitis (HSV-1) Epidemiology: - Worldwide distribution - >50% of world population is infected: 33% by 5 yo and 70-81% by adolescence - Humans are only reservoir for transmission - Transmited through close personal contact - Asymptomatic transmission is possible Factors triggering reactivation: - Emotional stress - Physical stress - Mild trauma

Describe the Lytic and Lysogenic Phage life cyclec (transduction)

Lytic: 1. Phage attaches to receptor site on another bacterial cell wall, penetrates it and inserts DNA 2. Phage DNA directs cell metabolism to produce viral components- proteins and copies of phage DNA 3. Empty phages heads are synthesized 4. Heads are packed with DNA 5. Collars, sheaths, and base plates have been attached to heads. Tail fibers are added last 6. Bacterial cell lyses, releasing completed infective phages *** GOAL= to replicate and get out (virulent). Phage DNA enters cell, replicates, synthesizes phage heads, assembles, and cell is lysed Lysogenic: 1. Phage is replicated along with the bacterial DNA prior to binary fission 2. Binary fission completed; each cell has the phage DNA incorporated *** GOAL= long-term-temperate; stable integration of a viral genome into bacterial genome; viral genome= prophage; dormant - Lysogenic conversion: prophage alters bacterial cell phenotype; outcomes ex: diphtheria, scarlet fever, botulism - DNA of phage may encode bacterial virulence factors (ex. Cholera toxin) - Prophage excises at insertion sequence when stressed (ex. DNA damage; UV irradiation)--> some become lytic, other exit the cell without lysis

Inhibition of the Cholinergic Receptor Signal Transduction (i.e. in the heart)

M2 receptor activation is mediated via the Gi protein, which opens K+ channels located in the SA node, AV node, and atrial cells - Adenyly cyclase is inhibited which reduces production of cAMP - This results in negative chronotropic and dromotropic effects

What types of drugs would you perscribe for Glaucoma in order to reduce intraocular pressure?

M3 (parasymp) agonist: to increase aqueous humor outflow-ciliary muscle - adverse effect: all M3 effects not related to aq. humor Alpha2 (Symp) agonist: decreases aq. humor production- ciliary epithelium - adverse effect: all alpha2 effects not related to aqueous humor Beta2 (symp) antagonist: decreases aq humor- ciliary epithelium - adverse effect all beta 2 receptors not related to aq. humor

Stimulation of the Cholinergic Receptor Signal Transduction

M3/M1 activation is mediated by the Gq protein, which causes increased activity of phospholipase C (PLC) and increased production of inositol triphosphate (IP3) and diacylglycerol (DAG). Subsequently, Ca2+ influx is increased Nn receptor activation opens a cation channel which leads to rapid influx of Na+ and Ca2+

Child Abuse

MANDATORY reporting for children up to and including age 17 - may have to sep. child from adult and then call sate department of child and fam services **** best to report when suspicious (err on side of caution)***** Can be phys. violence, neglect, psychological, sexual risk factors: <1yr, stepchild, premature, hyperactive, sick, developmental delay/disability signs of abuse: belt marks, fractures at various stages of healing or in pts <1, spiral fractures, bruises in unusual areas (back, inner thigh, buttocks), burns etc (usually soft tissue injuries) *** abused children may "act out" in school, be more aggressive, abuse substances, and become abusers ----- Shaken baby syndrome - brain injury caused by forceful shaking - sx: extreme irritability, diff staying awaker, breathing prob, poor eating, tremors, vomiting, pale/bluish skin, seizures, paralysis, coma - presentation: retinal hemorrhages, floppy body/extremities, subdural hematoma, increased head size Sexual abuse: reasons for raised suspision - unusual sexual knowledges - STDS in young children - recurrent UTIs - vaginal or anal trauma - excessive dependency on caregiver ** MUST REPORT all these

Describe the cardiovascular effects of adrenergic receptor activation

MAP= CO x TPR Alpha1 (increases TPR) - receptor activation will lead to constriction of blood vessels- baroreceptor reflex will cause bradycardia Alpha2 (can increase or decrease TPR) - local vasoconstriction at high concentrations. vasodilation due to decreased sympathetic output from the CNS - catecholamines (epinephrine, norepinephrine and dopamine) do not cross the BBB when administered intravenously- alpha2 effects are not as significant for drugs that act in the periphery Beta1 (increased HRx increased SV= increased CO) - receptor activation increases HR and contractile force resulting in increased cardiac output Beta2 (decreased TPR) - receptor activation causes vasodilation in skeletal muscle resulting in decreased peripheral resistance- if there is no alpha1-receptor activity- Baroreceptor reflex will cause tachycardia

What are some virulence mechanisms of viruses that can alter host defenses

MHC sequestation/inhibition - Both MHC-I and MHC-II - Interfering with MHC-I Ag presentation dampens CD8 responses - Interfering with MHC-II Ag presentation dampens CD4 responses and, therefore, Th1 responses Can occur through: - inhibition of TAP1/TAP2 - inhibition of proteasome - Inhibition of MHC syntehsis inhibition - Inhibition of MHC reinternaliztion, sequestration, degradation - Inhibition of MHC peptide loading, traffiking - Inhibition MHC reinternalization, sequestration, degradation Cell signaling - Since antiviral defenses, inclduing antigen presentation, rely on signaling pathways to respond appropriately, the Jak/STAT pathway is especially important in this contect, any viral component that can interfere with the proper signaling involved in antiviral defenses, at any stage of the pathway, can give the virus an edge over the immuns system Virokines & viroceptors - Virokines: viral homologues (or sometimes viral analogues) of host cytokines and chemokines - Viroreceptors: Viral homologues or analogues of the host cytokine/chemokine receptors that sequester (neutralize) host-derived cytokines and chemokines using membrane bound as well as soluble cytokine receptor homologues/analogues **End result= modulation of the hosts immune response by the virus Leukocyte killing: - Some viruses can induce apoptosis in leukocytes to dampen the immune response (macrophages, CD4 T lymphocytes) Immune-deprived tissues (immune-privileged sites): - Some viruses may infect sites where infalmmatory processes may be detrimental to the host (ex. eyes--> blindness; testicles--> sterility; CNS--> encephalitis/meningitis; placenta/fetus --> miscarriage Viral structure: - many naked viruses can withstand gastric pH and bile salts dsRNA-binding proteins (anti-IFN-alpha effects) to avoid detection by PRRs - recognition of PAMPAs leads infected cells down a pathway of self-destruction (apoptosis and autophagy) CTL espace mutants: Genetic drift--> Generation of mutants --> Error-prone polymerase - Under selective pressure, mutants, become "invinsible" to the immune system - Genetic drift is also the mechanism behing antigenic drift, a process whereby the antigenicity of viruses is modifed as they spread through populations- further developed in the influenza - If these differense make the viruses non-antigenic, these become escape mutants (CTL escape mutants) i.e. viruses that are no longer subjected to CTL responses

Linezolid

MOA - Binding of the 50S ribosomal subunit at a specific site near to the 30S ribosomal subunit - Binding inhibits the formation of the initiation complex - Ultimate effect: bacteriostatic

Tyramine

MOA: - A false NT that is taken up by the adrenergic neurons where it is transformed into octopamine, a very weak adrenergic agonist - Octopamine is stored in the adrenergic vesicles, gradually displacing NE Pharmacokinetics: - it is a dietary amine found in cheese, red wine, and fermented foods - it is metabolized and inactivated by monoamine oxidase (MAO)- in pts taking MAO inhibitors tyrosine is absorbed into the blood and taken up into sympathetic neurons Adverse effects: - If large amts of tyramine contianing foods are ingested together with a MAO inhibitor, it may cause sympathomimetic actions (including a potentially lethal hypertensive crisis), due mainly to NE release

Methyldopa

MOA: - A false NT which is taken up by the adrenergic neurons where it is transformed into methylnorepinephrine, an alpha2-agonist (decreased symp, decreasing BP) - Activation of CNS alpha2-adrenoreceptors by methylnorepinephrine reduces central adrenergic tone (the central effects are similar to those of clonidine) Therapeutic uses: - Hypertension (first choice drug in pregnancy**)

Pralidoxime

MOA: - spontaneous hydrolytic regeneration of phosphorylated acetylcholinesterase - pralidoxime has a high affinity for the phosphorous atom and can rapidly regenerate the enzyme if the complex did not undergo aging Pharamacological effects: - the reactivating action of pralidoxime is most pronounced at the neuromuscular junction Therapeutic uses: - Reverse poisoning by **organophosphate insecticides (pralidoxime is not effective in reversing central effects of organophosphates bc it CANNOT cross the BBB) ** Pralidoxime ONLY works for organophosphates-- DOES NOT work for carbamates (neostigmine etc.)

Phentolamine

MOA: Competitive inhibition of alpha1 and alpha2 receptors Uses: (phenoxybenzamine was main choice for pheochromocytoma) - Pheochromocytoma: management of hypertensice episodes during the perioperative period - Extravasation management: prevent dermal necrosis after extravasation of NE (alpha1 activation causes vasoconsriction that can lead to ischemia and necrosis) - Local anesthetic reversal- relaxation of the blood vessels allows the local anesthetic to diffuse away from the injection site Pharmacological Effects (same as phenoxybenzamine) - Decrease in peripheral resistance due to inhibition of alpha receptors on blood vessels - Increase in CO due to reflex tachycardia. Cardiac stimulation is further increased bc there is no neg feedback to stop the release of NE from cardiac nerve endings bc presynaptic alpha2 receptors are blocked Adverse effects: - Hypotension - Tachycardia

Phenoxybenzamine

MOA: IRREVERSIBLE inhibition of alpha1 and alpha2 receptors (very long duration of action) - Endogenous catecholamines will NOT be able to compete/displace the drug Effects: - Decrease in peripheral resistance due to inhibition of alpha receptors on blood vessels - Increase in CO due to reflex tachycardia. Cardiac stimulation is further increased bc there is NO negative feedback to stop the release of NE from cardiac nerve endings bc presynaptic alpha2 receptors are blocked Clincal uses: Pheochromocytoma (** irreversible drug best fomr a treatment bc no matter how much agonist is added it can not be overcome) Adverse effects: - Orthostatic hypotension - Tachycardiac - Miosis (alpha1) - Nasal congestion

Nicotine

MOA: Nicotine activated nicotinic acetylcholine receptors (Nm and Nn). Large doses of nicotine cause a depolarization blockaged Clinical Use: - Aid smoking cessation for the relief of nicotine withdrawal syndromes Acute Toxicity**: Poisoning due to accidental ingestions; most likely in children under 6yo due to ingestion of vaping liquied, tobacco or nicotine patches/gum - The early effects of nicotine are due to nicotine receptor stimulation and include: excess salivation, sweating, confusion, cough and elevated blood pressure - The later symptoms are a result of nicotinic receptor inhibition and these include: skeletal muscle endplate depolarization which may lead to breathing difficulty (paralysis of the diaphragm) -- if too much stimulation there is downregulation of receptors

How does the Opinions of the Code the Council on Ethical and judicial affairs use the words must, should and may

MUST: an action that is ethically required for physicians- from the perspective of eithcs and professionalism, such actions are near-aboslute obligations, not matters about which phys may use judgement or discretion SHOULD: strongly recommended as matter of professional ethics, but which may have some exceptions- used to indicate what is expected of a phys. in most instances, absent special circumstances or considerations- indicates that ethically there is some latitude for phys judgment and discretion MAY: action is ethically permissible when qualifying conditions set out in the opinion are met

Antibiotics that blcok the 50s ribosome (protein syn. inhibitors)

Macrolides - via blockade of translocation reaction Chloramphenicol: - via blockade of transpeptidation reaction Quinupristin: - via blockade of translocation reaction Dalfopristin: - via induction of a conformation change in the 50s ribosome Linezolide - via blockade of the initiation complex

Describe the plasma membrane of bacteria

Made of proteins within a phospholipid bilayer - No sterols (except mycoplasmas) - Contains cardiolipin (which is not found in eukaryotic plasma membranes) Function of Plasma membrane: - Barrier against aqueous ions (allows gradients, control over osmotic balance- whats moving in and out and how fast) - Most of the functions come from the proteins within the membrane: metabolite and nutrient transport, biosynthesis of lipids, polysaccharides, peptidoglycan NOTE: if we find ways to disrupt the plasma membrane that bacterial cell is going to die

How is Peptidoglycan synthesis used as a drug target?

Major target: - Unique to bacteria - Essential for most bacteria (so it is a major target) Beta-lactams (like penicillins, cephalosporins, etc.): - inhibit transpeptidases - so new PG is weak, leads to cell lysis as autolysis continue to function (no linkage and structure falls-> cell lysis) Glycopeptides (Ex. Vancomycin) - Bind the stem peptide D-ala-D-ala - Prevent transpeptidation and transglycosylation (shut down cleavage) Bacitracin (In Polysporin) ** Inhibits one of the most important parts of the PG syntheis bactoprenol-PP - Prevents recycling of bactoprenol-PP (this prevents one of the most important parts of PG synthesis bactoprenol-P) - Affects synthesis of several cell-surface polymers Fosfomycin (phosphomycin) - Inhibits MurA (at beginning building monomer for first time with tail thats present) * there are also drugs that can inhibit MurB, C, D which are all enzymes that may propel this reaction forward Cycloserine (antimycobacterial) - Inhibits alanine racemase (No L-Ala --> D-ala in the beginning) and D-ala-D-ala synthetase Tunicamycin - Nucleoside analogue - - Prevent transfer of NAM-P to Und-P Also target for innate antibacterial lysozyme - Cleaves bond between NAG and NAM - In mucus, tears, saliva O-acetylation of PG inhibits lysozyme - Staphylococcus aureus Outer membrane impedes access of lysozyme - outer membrane in gram negative (inherent resistance to lysozymes)

"Pharmacokinetic Antagonism"

Many drug interactions occur bc one drug affects metabolism of another drug Consider: - Drug A increases metabolism of Drug B - Drug B will have reduced plasma concentration and shorter duration of action - Drug A is inhibiting the effects of Drug B - Drug A is a "pharmakokinetic antagonist" of Drug B

How are transcription and translation in prokaryotes good drug targets?

Many enzymes significantly different from eukaryotic homologs Important targets include: DNA synthesis: - Topoisomerases (quinolones) - Block nucleotide synthesis and folate synthesis (including sulfonamides, trimethoprim sulfamethoxazole) - Metronidazole- disrupts DNA RNA synthesis: - Block mRNA synthesis; RNApol (rifampin blocks RNA synthesis) Protein synthesis: - Lots of targets and lots of drugs

What happens to proteins after they are translated in prokaryotic translation?

Many proteins (ex. exotoxins) are translocated, i.e. exported Barriers to this: - Gram-positive: Cytoplasmic membrane and peptidoglycan layer - Gram-negatives: periplasmic space and outer membrane ** these are barriers to proteins being exported NOTE: the general secretory pathway (GSP) is used for both gram+/- GSP is enough for Gram + secretion or for Gram-negative transport to the peptidoglycan or periplasm BUT - Gram-negative bacteria have to get their extracellular secreted proteins across another membrane (outer membrane) - Five pathways I-V in Gram-negative bacteria (actually, there are many more for both gram-positives and negatives and more are being discovered all the time) NOTE: - *****Type III & IV: syringe-like apparatus that injects the proteins across a third membrane, that of a host cell. Type III is also termed "injectisome" - these are used to get gram negative bacteria out! *****

Rectal drug administration

May be used for systemic or local effects Absorption pattern: - primarily by lipid diffusion - erratic and variable Advantages: - partially bypasses first pass effect - bypasses destruction by stomach acid - ideal if drug causes vomiting - ideal in pts who are vomiting or comatose Disadvantages: - drugs may irritate rectal mucosa - not a well accepted route

DNA vaccines ( a type of active immunization)

May be useful for infectious agents requiring T cell and B cell responses but are not appropriate as a live vaccine - HIV and plasmodium falciparum are two pathogens which fit these criteria - With DNA vaccines, the gene for a protein that elicits the protective immune response is cloned into a bacerial plasmid that allows for the expression of the protein by a human cell - The plasmid is injected into the muscle or skin of the vaccine recipient where it enters host cells and uses host cell machinery to express the encoded antigenic protein - The protein can exit the cell where it can be recognized by B cells, presented as peptide to CD4 T cells by pAPCs in an MHC class II-restricted fashion, or presented in an MHC class I-restricted fashion to CD8 T cells - Thus far, results with DNA vaccines have not lef to effective, approved and marketable products

Risk reduction/Risk difference (RD) or Attributable Risk (AR)

Meausre of association that provides info about absolute effect of exposure or the excess risk of disease - Diff between incidence rates in exposed and non exposed groups AR= (a/a+b) - (c/c+d) AR= Ie - Io **Risk difference is used to quantify the risk of disease in exposed group that can be considered attributable to the exposure by removing the risk of disease that would have occurred anyway due to other causes (ex. the risk in the unexposed group) ** If there is no association between exposure and disease, there will be NO difference between the incidence rates in the exposed and non-exposed groups, so RD= 0**

Ganglionic Blockers (Nn)

Mecamylamine Hexamethonium Trimethaphan ** Ganglionic blockers have very limited use bc of the broad rang of undesirable effects- due to blockade of nicotinic receptors in the symp and parasymp ganglia they stop all autonomic outflow- this is useful for research purposes, and is sometimes used to test students understanding of autonomic nervous system signaling Mecamylamine MOA: non-depolarizing competitive inhibitor of nicotinic receptors (Nn) Pharmacological effects: The opposite of predominant tone Cardiovascular system: - increase in HR - decreased CO (in spite of the increase in HR, bc the peripheral venous pooling decreases the preload) - decrease in venous tone and peripheal vascular resistance (which leads to hypotension, mainly in the upright position) Therapeutic uses: Hypertension

MOA of Chloramphenicol

Mechanism of antibacterial effect: 1. Binding reversible to the 50S subunit of the bacterial ribosome 2. Blockade of the transpeptidation rx. (which is catalyzed by peptidyl transferase) ----> BACTERIOSTATIC

MOA of tetracyclines & glycycyclines (Doxycycline & Tigecycline)

Mechanism of the antibacterial effect--> step one, reach cytoplasm Penetration through the cell envelope by: 1. Diffusion through the aqueous channels (porin proteins) of the outer bacterial membrane 2. Active transport across the inner membrane by an energy-dependent system (eukaryotic cells lock this system and this explains the high selectivity of tetracylclines) Step two: Inhibition of ribosomal protien synthesis 1. Binding reversibly to the 30S subunit of the bacterial ribosome 2. Preventing the access of the aminoacyl tRNA to the acceptor site of the ribosome (this inhibits the incorporation of the next AA into the peptide chain) ---> BACTERIOSTATIC

MOA of Macrolides and Lincosamides (Erythromycin and Clindamycin)

Mechanism of the antibacterial effect: Inhibition of normal protein synthesis by the following actions: Reversible binding of the 50S subunit of the bacterial ribosome - blockade of translocation of the newly synthesized peptidyl tRNA from the acceptor site (A) to the peptidyl site (P) of the 50S ribosomal subunit - blockade of transpeptidation reaction (some compounds) Features of the antibacterial effects: - Ultimately: mainly BACTERIOSTATIC (these drugs can be bactericidal when given in high concentrations against very susceptible organisms- not the normal case)

Medical Phone calls and Emails

Medicare and many private insureres do NOT pay for "telephone visits" but some will if calls are properly coded and documented ~ 50% of calls to PCP office during regular consulting hrs are for clinical problems and most are handled effectively over the phone without an immediate office visit - typically very brief, freq. seeking advice and reassurance (anxiety and psychological stress) rather than diagnosis and tereatment - phone encounters should be recordered in the chart for both clinical and legal reasons - effective phone consult depends on good communication skills (physicians perceptions of problem may be diff than pts) Emails - Email can be used for non-urgent consultations, lab results, appointments, prescription refills, etc. AMA guidelines: - physician-clinician agreement for informed consent to use email (discussed and signed) - inform pt about privacy issues - establish turnaround time and types of interactions permitted over email - develop archival and retrieval mechanisms - avoid group mailing where recipients are visible to each other - avoid anger, sarcasm, criticism, references to third parties - include physicians full name, contact info, and importance of alternative forms of communication for emergencies

Mechanisms of Defense

Mental processes (usually UNCONSCIOUS) that: - help manage inner conflict - protect against anxiety and - maintain psychic equilibrium ** "evoked by the ego as an attempted means of coping with an otherwise consciously intolerable situation" Continuum of Defenses: Primitive --> Neurotic --> Mature (SASH) Primitive: - projection - splitting - acting out Neurotic: - rationalization - intellectualization - reaction formation (and many more..) Mature (SASH) ** Helathy relationship with reality, req. conscious awareness, result in optimal adaptation - Sublimation (i.e. channeling emotions into something that is not harmful but helpful) - Altruism - Suppresion (i.e. chosing not to think of something at the moment) - Humor

Biotransformation (Metabolism) of drugs

Metabolism leads to the termination or alteration of a drugs biologic activity Drugs can be metabolised in 3 ways: 1. Pharmacologically Active drug --> Pharmacologically INACTIVE metabolite (Most common scenario) 2. Pharmacologically active drug --> Pharmacologically active metabolite with the same or different pharamcological activity 3. Inactive drug (prodrug)--> Pharmacologically active metabolite Biotransformation reactions can be assigned to one of 2 major categories called phase I and phase II reactions - Metabolism by phase 1 followed by phase 2 produces a metabolite that is highly water soluble and readily eliminated from the body (sometimes phase 2 reactions occur directly) - Phase 1 reactions ex. oxidation (most common), reduction, or hydrolytic reactions

MRSA

Methicillin introduced in 1959. MRSA appears by the early 1960s - mecA is carried on a mobile genomic element: Staphylococcal Chromosmal Cassette (SCCmec) --> which encodes an altered penicillin binding protein (PBP 2a) FYI: - There are 4 types of SCCmec, each with a varying array of drug resistance - SCCmec II and III are found in many nosocomial MRSA strains. These chromosomes harbor other antibiotic-resistance genes conferring resistance to aminoglycosides, tetracyclines, erythromycin and clindamycin - CA-MRSA carries SCCmec IV which only carries the mecA gene

The time a drug takes to reach steady state CAN NOT be increased or decreased. BUT the steady state concentration CAN be increased by which two methods?

Method A: Increase the drug dose but maintain the same dosing interval- results in wider fluctuations between the peak and trough concentrations or Method B: Maintain the dose but decrease the dosing interval- results in smaller fluctuations between the peak and trough concentrations

What are some techniques that can be used to diagnose fungal infections?

Microscopy: fungal cultures and antifungal susceptibilities for systemic disease *** Microscopy-Rapid methods (detection directly from patient specimen)---> KOH wet mounts (plain or with calcofluor white) - KOH degrades human cells - Skin scales or minced biopsy tissue is placed in a drop of 10% KOH on a glass microscope slide, cover slipped, wamred and let rest for 10 minutes to release the fungal elements - To view on the light microscope you must reduce the light or you will never see unstained fungi - You may use calcofluor white; read with fluorescent scope ** Smell + KOH= Amine test (smell indicates that dead bacteria is present) Serology: detection of patient antibodies to the fungus for systemic disease PCR: for some fungi causing systemic disease Fungal products: detection of Skin testing (available for a few): only demonstrates exposure

During specimen collection and processing- what are some things you should be certain of

Minimize contamination: - from actual site of infection - minimally contaminated with material from adjacent tissues, organs or secretions Appropriately timed: - Ex: smears for malaria diagnosis should be collected at different times during the day bc parasitemia can be intermittent - Obtained before administering antibiotics In the appropriate container/device: - Follow guidelines Sufficient quantity: - Insufficient volumes of specimens can compromise the validity of results Properly labeled: - Pt name - ID number - Specimen source - Ordering physician - Date/hour collected

Defects in Mismatch Repair

Mismatch repair (MMR) complex: MLH1, MSH2, MSH6, and PMS2 Mutations in MMR genes--> deficiency in mismatch repair--> microsatellite instability (MSI)*: expansion or contraction of microsatellites (tandem repeats of one to six nucleotides)--> dysregulation of cell growth --> neoplasia Designation***: - Tumors with high MSI: MSI-H - Tumors with low MSI: MSI-L Associated Neoplasms: Germline MMR mutation--> inherited colon cancer [Hereditary Non-polyposis colon cancer (HNPCC) Syndrome] - cecum and ascending colon - single adenomatous polyps - colon carcinoma arising outside polyps - extracolon carcinomas: stomach, endometrium, and ovary Sporadic MMR mutation--> Sporadic Colon Cancer

What are the differences between the mitochondrial (intrinsic) pathway vs. Death receptor (extrinsic) pathway of apoptosis?

Mitochondrial (Intrinsic): - Cell injury (growth factor withdrawal, DNA damage (by radiation, toxins, free radical), protein misfolding (ER stress) - BCL2 family sensors - BCL2 family effects (BAX, BAK) - Cytochrome C and other pro-apoptotic proteins - Initiator caspases - Executioner caspases (**** REMEMBER PROCASPASE 9 *****) - breakdown of cytoskeleton and endonuclease activation --> nuclear fragmentation--> cytoplasmic bled --> apoptotic body w/ ligands for phagocytic cell receptors --> phagocytosis Death receptor (extrinsic) pathway: **** REMEMBER PROCASPASE 8!!!! - receptor ligan interactions (Fas and TNF receptor)--> adaptor proteins --> initiator caspases (from here same steps as mitochondrial) Intrinsic pathway uses procaspase-9 Extrinsic uses procaspase-8 -- these then give active caspases then executioner caspases which lead to apoptosis

Schistosomiasis

Mode of infection: direct skin penetration by cercariae (SWIMMERS ITCH) Sites of infection: - S. mansoni - intestinal blood vessel - S. japnicum- intestinal blood vessel - S. haematobium- urinary bladder blood vessel Diagnosis: Eggs in feces: - S mansoni- huge lateral spine - S japonicum- rudimentary lateral spine Eggs in urine: - S haematobium- terminal spine (associated with squamous cell carcinoma of the bladder) ** Be able to identify typical intense eosinophil response ** Eosinophilia is a hallmark of helminths NOT protozoa

Adaptive immune responses

Monocyte-derived phagocytic cells at site of infection recognize pathogen and 1. destroy it on site 2. pick it up for processing and antigen presentation This is often done by diff. monocyte-derived phagovytic cells, but prior to this happening, pathogen must first be recognized via PAMP-PRR interactions that occur between the pathogen and the macrophage or dendritic cell, followed by the consequent integration of all intracellular signaling events that take place when these PRRs are engaged TLRs= best ex of PRRs that recog. viral infections - dsRNA recog. by TLR-3 - ssRNA virus by TLR-7 - DNA viruses recof by TLR-9 Other TLRs involved= TLR-2, TLR-4, TLR-8, and TLR-10 RIG-1 Pathway is also important: - Viral recog. by macrophages leads to activation of appropriate genes that are req. to address this particular pathogen: phagocytosis and destruction or uptake for antigen presentation - The particular subset of macrophages that is actvated by PAMP-PRR interaction is said to be innately activated. When dealing with viruses (or other intravelular pathogen), this translates mainly in IL-12 and TNF-alpha secretion by macrophage and dendritic cell IL12 will create the milieu tht will influence naive CD8= and CD4+ T lymphocytes to engage in Th1 response upong antigen presentation in proximal secondary lymphoid tissues At same time immature DCs and macrophages at site of infection endocytose/phagocytose the pathogen (mainly for purpose of MHC-II- resitrcted Ag presentation) or are infected (for the purpose of MHC-I restricted Ag presentation Pathogen engulfment of infection makes DCs mature as they migrate to proximal secondary lymp tissues where they will present pathogen-derived antigen to naive CD8+ and CD4+ T lymphocyte Monocyte-derived phagocytci cell antigen uptake entails changes in proteasomal activity [proteasomes are replaced by immunoproteasomes (the beta1, beta5, and beta2 subunits are replaced by the LMP2, LMP7, and MECL-1 subunits respectively, among others) which have greater catalytic activity and are better suited to derive more antigenic peptides (ex. they are faster and generate more antigenic peptides) that degrade thepathogen for the purpose of MHC-I-restricted antigen presentation, as well as MHC-I and MHC-II and co-stiumulatory molecules (CD86) up-regulations and cell surface expressions Hence in the case of the most specialized professional APCs the highly phagocytic immature DC is transformed into a mature DC, which is a highly efficieny antigen presenting cell through botuh MHCI and MHCII restricted antigen presentation *** CD80 is expressed on surface of some subsets of actvated B lymphocytes, CD86 is the co-stimulatory molecule present on most pAPCs

Phenotype (observable traits) that can be used for classification of bacteria?

Morphology: cell shape and size - The cell shapes that occur among unicellular true bacteria: Coccus, Rod, Curved, Spiral, and Filamentous * Often shapes derived from Greek - Streptos: twisted, as in a twisted chain (Streptococci: stain purple in long twisted chain) - Staphyle or Staphule: bunch of grapes (Staphylococci: stain purple like hanging grapes) ** Morphology varies widely on a plate Staining reactions: especially gram staining reaction

What is the usual site of replication for DNA viruses vs. RNA viruses

Most DNA viruses replicate in the nucleus - EXCEPT for the poxiviridae which encode their own cytoplasmic factories Most RNA viruses replicate in the cytoplasm - EXCEPT for the Retroviridae, Orthomyxoviridae, Deltaviridae

Microbial resistance to Macrolides and Lincosamdes (Erythromycin and Clindamycin)

Most strains of staphylococci are now resistant to erythromycin and resistance may emerge during treatment of an individual pt Resistant strains of P. neumoniae are common Resistance is crossed between diff. macrolides and between macrolides and lincosamides Mechanisms of resistance are usually plasmid-encoded, including: - increased activity of the multidrug efflux pump or reduced cell membrane permeability - modification of the ribosomal binding site which decreases drug binding (so called ribosomal protecting) - macrolide hydrolysis by bacterial esterases (mainly produced by enterobacteriaceae)

Differentiate between Myasthenic vs Cholinergic Crisis

Myasthenic Crisis (Disease) - A rapid increase in muscular weakness due to worsening of the disease - Anticholinesterase drugs will help with the symptoms of the disease Cholinergic Crisis (Drugs) - A rapid increase in muscular weakness that may be coupled with adverse muscarinic effects of anticholinesterase drugs such as sweating, salivation, diarrhea, and miosis - Anticholinesterase drugs will make the symptoms WORSE

Trichinella spiralis (Trichinosis)

NO eggs in feces, larvae produced - NO external phase - DEAD END- transmission by carnivorism Mode: ingestion of infected meat (cysts) Site: adult in intestine Diagnosis: larvae form cysts in muscle ** Muscle pain/muscle biopsy

Differentiate between a naked and enveloped virus

Naked virus: Protein capsid + Nucleic acid genome Enveloped virus: - Envelope on the outside with envelop proteins (spikes) - Matrix beneath that (matrix connects nucleoprotein/capsid to envelope) - Nucleocaspid (filamentous) inside composed of nucleic acid and nucleoprotein Other viral components include: - Enzymes: proteases, polymerases, neuraminidases, integrases - Non-genomic NAs: primers, tRNAs, mRNAs - Other proteins

Describe microbial resistance to Aminoglycosides

Natural resistance occurs in bacteria that: - have cell walls impermeable to the drug (ex. many gram+ bacteria) - produce inactivating enzymes - are anaerobic bacteria (penetration to cytoplasm req. oxygen) - lack the receptor on the ribosomal structure- some of these features can also be acquired, so that a sensitive strain can become resistant Acquired resistance occurs in bacteria that have acquired some of the above mentoined features: - most freq. type of resistance (production of inactivating enzymes) is plasmid-encoded and can be transferred by bacteriophage to other bacteria Cross-resistance can occur among aminoglycosides Can occur via 1. Plasmid-mediated production of group transfersases [inactivate drug](phosphoryl-transferase, adenylyl-transferase, acetyl-transferase) - most important mechanism**, can lead to rapid development of resistance - Amikacin is less vulnerable to inactivation by such enzymes 2. Mutation-induced change of the recpetor protein on the 30S robosomal subunit - it can lead to a very rapid development of resistance - it affects mainly streptomycin and is rare reason for resistance 3. Decreased permeability of the bacterial cell surface to the drug - this mechanism may result from mutation or deletion of a porin protein involved in transport

Describe microbial resistance to beta-lactam antibiotics

Natural resistance to beta-lactams occurs in bacteria that: - lack peptidoglycan cell wall (ex. mycoplasma, chlamydiae) - have cell membranes that are impermeable to the drug (many gram-negative bacteria) - are beta-lactamase producing organisms - have PBPs with low affinity for the drug Some of these features can also be ACQUIRED, so that a sensitive strain can become resistant - Acquired resistance develops in many species (cocci, bacteroides, etc.)--- acquired resistance is mainly extrachromosomal and is encoded in a plasmid that can be transferred to other bacteria - Cross-resistance occurs among ALL beta-lactamase sensitive penicillins - Partial cross-resistance occurs between beta-lactamase resistant penicillins and cephalosporins Mechanisms of acquiring microbial resistance to beta-lactams include: 1. Production of beta-lactamase enzymes (by far most important mechanism) - beta-lactamases hydrolyze the beta-lactam ring so producing penicilloic acids which are devoid of antibacterial activity- genes controlling beta-lactamase production can be both chromosome and plasmid encoded 2. Development of PBPs which have decreased affinity for the antibiotic (mechanism for penicillin resistance in penumococci and methicillin resistance (MR) staphylococci). The genes controlling production of changed PBPs are chromosome encoded 3. Decreased permeability of the cell membrane to the drug (the mechanism for penicllin resistance in many gram negative bacteria) 4. Development of an active efflux pump (the mechanism for penicllin resistance in some gram negative bacteria)

Liquefactive Necrosis

Necrosis with loss of cell outlines and tissue architecture Mechanism: 1. Neutrophil influx and release of lytic enzymes 2. Digestion of cell carcasses Causes: - Bacterial infection: abscess - Preexisted coagulative necrosis, ex. ischemic necrosis of the brain Histology: - structureless tissue debris (no cellular outlines) - PMNs (neutrophils) Gross appearance: - soft and wet tissue - color depends of presence of blood (pale/grey= ischemic, red, brown, or black= extravasation of blood)

Coagulative Necrosis

Necrosis with perservation of cellular outlines at least for some days (usually tissue architecture is also preserved) Mechanism: - Intracellular acidosis and calcium influx - Denaturation (preservation) of structural proteins and enzymes - No proteolysis Most common cause: Ischemia - Infarction: Ischemic Necrosis Histology: acidophilic (eosinophilic) coagulated anuclear cells Gross appearance: dead tissue is dense and dry, cut surface is white-grey Outcome: Enzymatic digestion (liquefaction) - cerebral infarct in a few days - myocardial infarct in a few weeks

Necrosis vs. Apoptosis

Necrosis: - enlarged cells (swelling) - Nucleus: pyknosis, karyorrhexis, karyolysis - plasma membrane disrupted - cellular contents undergo enzymatic digestion; they may leak out of cell - adjacent inflammation is frequent - invariably pathologic (culmination of irreversible cell injury) Apoptosis: - reduced cells (shrinkage) - nucleus undergoes fragmentation into nucleosome-size fragments - plasma membrane intact; altered structure, especially orientation of lipids - cellular contents intact; may be released in apoptotic bodies - NO adjacent inflammation - Often physiologic, means of eliminating unwanted cells; may be pathologic after some forms of cell injury, especially DNA damage

Differentiate between Necrosis vs. Apoptosis

Necrosis: morphologic changes that follow cell death (after irreversible injury) in living tissues - cellular "homocide", affects groups of cells - seen only in pathologic conditions - induces acute inflammatory response (neutrophil influx) Structural changes: - Reversible injury --> swelling of ER and mitochondria, membrane bleds--> progressive injury --> breakdown of plasma membrane, organelles and nucleus; leakage of contents (with inflammation, myelin figures and amorphorous densities in mitochondria) Apoptosis: (in greek means a falling off)- morphologic changes that follow programmed cell death in living tissues - cellular "suicide", affects single cells - seen in BOTH physiologic and pathologic conditions - apoptotic bodies are readily cleared by macrophages Structural changes: - Condensation of chromatin, membrane blebs--> cellular fragmentation and apoptotic body --> phagocytosis of apoptotic cells and fragments

What is expected at each developmental milestone?

Neonatal period (0-1month): Primitive reflexes - rooting and sucking - grasp - moror or startle reflex - positive babinski (indicates lack of myelination of corticospinal tract) Infancy (1-12 months) - walk at 12 months - 6 months half way there "sit at six" - ** 2 months= first time we really check mile stones- lifts had whne hears voices, smiles bc can follow both parents ,one on eaither side of midline (voice-spotting baby) - 4 months: rolling, laughing and cooing, midline and reaching for toys that he will cram into mouth (happy chappie) - 6 months: sitting up on sidewalk, transferring rake from hand to hand with babbling at ppl he thinks he recognizes (street-corner bby) - 9 months: crawls to windoze, pulls to stand to see out, points at stranger in yeard and says "mama" to get attention of parents (watch-dog bby) - 12 months: walking at u, snapping pincers, repeating one word, play patty-cake and peekaboo b4 waving bye bye (playful walking zoombie)

List the Cholinergic Receptor Types and Locations

Nicotinic: parasympathetic, sympathetic, and somatic - Nicotinic neuronal (Nn): in ganglionic neurons, adrenal medulla, and CNS - Nicotinic muscular (Nm)- somatic NS: in skeletal muscle- neuromuscular junction Muscarinic: parasympathetic nervous system - M1: in ganglionic neurons, CNS - M2: in heart, smooth muscles - M3: in smooth muscles *** Our focus during autonomic drugs is the ANS- however due to ACh signaling via the nicotinic muscular (Nm) receptor, we have to consider potential effects on muscle; the somatic NS

List the Cholinergic Receptor Signal Transduction

Nn (Ligand gated-ion channel): open cation (Na+/K+ channel) Nm (Ligand gated-ion channel): open cation (Na+/K+ channel) M1 (Gq): increases IP3 and DAG, inceases Ca2+, Closes K+ channels M2 (Gi): Decreases cAMP, open K+ channels M3 (Gq): increases IP3 and DAG, increases Ca2+

Treatment, Prevention, and Control of Varicella-zoster virus

No treatment is usually necessary for children - but treatment could be necessary in adults, immunocompromised and ppl with shingles ACV, famciclovir and valacyclovir have been approved for treatment - VZV DNA polymerase is much less sensitive to ACV treatment than the HSV enzyme, requiring larger doses of ACV or the improve pharmacodynamis of famciclovir and valacyvlovir No good treatment, but analgesis and other painkillers, topical anesthetics, or capsaicin cream may provide some relief from the postherpetic neuralgia that follows zoster **Early exposure in children is encouraged as it offers life long immunity- exposure is not envouraged for immunocompromised VZIG: can provide protection to immunocompromise- it is prepared through the pooling of plasma from seropositive ppl - VZIG prophylaxis can prevent viremic spread leading to disease but is ineffective as a therapy for pts already suffering from active varicella or herpes zoster disease Live attenuated vaccine for VZV (Oka strain) has been licensed for use in US and elsewhere and is administered after 2 y of age on same schedule as the measles, mumps and rubella vaccine ---> the vaccine induces production of protective antibody and cell-mediated immunity * A stronger version of this vaccine is available for adults older than 60 yrs; its boost antiviral responses to limit the onset of zoster

Development of Sustained Angiogenesis in cancer

No vessels in neoplasm <1-2mm in diameter - Hypoxia--> p53 release--> apoptosis Angiogenic switch - Hypoxia--> HIFs stabilization --> activation of transcription of VEGF and basic FGF (bFGF)--> proliferation of endothelial cells and growth of new capillaries toward the tumor

Levels of Measurement

Nominal/Categorical: - Categories (i.e. names) one group not better than another just diff ex. Gender, ethnicity, presence, or absence of disease, race NO value in order Ordinal: - data that can be ranked, not necessarily numbered - one ranking not necessarily measurably better than another (ex. A not two times better than B ex; Grades and olympic medals Interval: - QUANTIFIABLE or MEASURABLE - DATA can be ranked - Zero does NOT represent absence of characteristic - still not directly comparable (ex. 100*F is not twice as hot as 50*F0 - ex. Altitude, IQ, and temp (Fahrenheit and Celsius)- 0IQ is not absence of intelligence and 0*C and F* are not absence of heat - Many possible values across a continuum Ratio: - Quantifiable or measurable - "highest" level of measurement - Zero is absence of characteristic; therefore, ratios of Variables can be made - Ex: Height, temp (Kelvin, 0*K is temp at which molecules cease to move), weight, BP, lab values - many possible values across a continuum

Carbon Monoxide (CO)

Non-irritating, colorless, tasteless, odorless gas Source: - incomplete oxidation of carbonaceous materials - automotive engines (car exhaust) - industrial processes using fossil fuels, wood, and charcoal burning with an inadequate supply of oxygen - cigarette smoking inhlation - leaking heating appliances - chronic poisoning in individuals working in confined environments with high exposure to fumes (tunnels, undergorund garages, etc.)

Barrett Esophagus

Noraml pale grey esophageal mucosa (squamous epithelium) and gastroesophageal junction --> Barrett esophagus. Red velvety mucosa (columnar/intestinal type epithelium) Morphologi changes in the affected part of the esophagus? Columnar (intestinal metaplasia) (Normal squamous epithelium is replaced by specialized columnar epithelium with scattered goblet cells)

How is Phenoxybenzamine a Non-competitive (irreversible) antagonist at the alpha 1 receptor?

Norepinephrine (NE) acts at alpha 1 receptors - increased effect with increasing concentration of NE Phenoxybenzamine (at both 1-100micromolar conc) - binds COVALENTLY to alpha 1, decreasing the number of available receptors - NE is added at increasing concentration - NE CAN NOT have maximal effect as there are fewer receptors available - curve moved to left and down in the Effect (%max) vs. NE conc (log) curve ** Non-competitive antagonist bind receptor making it unavailble for agonist --> decreasing signal transduction (decreases efficacy of agonist)

What finding will indicate an IRREVERSIBLE injury to cardiomyocytes?

Nuclei undergo karyorrhexis

Describe Renal Excretion

Occurs by glomerular filtration, tubular secretion, and tubular reabsorption Glomerular Filtration: - Passive process: driven by hydrostatic pressure within the glomerular capillaries - Occurs for molecules with a MW < 500 - Protein binding decreases filtration - Glomerular integrity and total number of functioning nephrons will affect filtration Active Tubular Secretion: - An active process: carrier mediated requiring energy and occurs in the proximal tubules - Capacity limited and may become saturated - Maintains physiological pH by secreting substances into tubular fluid: K+, H+, NH4+, Cr, Urea, some hormones, drugs - Drugs with a higher affinity for the transport system can inhibit the secretion of other drugs with a lower affinity. Two active secretion systems: 1. Weak acids (organic anion transporter, OAT) 2. Weak bases (organic cation transporter, OCT) Tubular Reabsorption: - can be active or passive process wich occurs in the distal tubule - occurs passively for lipid soluble and unionized drugs - tubular cell membranes act as a barrier to reabsorption - reabsorption depends on: molecular weight, lipid solubility, ionization (recall how changing the pH affects reabsorption- ion trapping discusion PK1) - may also depend on urine flow rate ****Glomerular Filtration Rate (GFR) provides an excellent measure of the filtering capacity of the kidneys - the total kidney GFR is equal to the sum of the filtration rates in each of the functioning nephrons Normal values: apprx. 130ml/min per 1.73m^2 in young men and 120ml/min per 1.73min^2 in young women

Herd immunity

Once a certain proprtion of a population has achieved immunity, the natural transmission of a pathogen in that population can be halted; this phenomenon is which is referred to as herd immunity

Enteral administration can involve oral, sublingual and buccal routes- which is the most common route for dose administration?

Oral route - Oral dosage form must be designed to account for: extreme pH ranges, presence or absence of food, degradative enzymes, varying drug permebility in the diff regions of the intestine, and motility of the GI Process of absorption may be affected by: - physiochemical, formulation, physiological and clinical factors Enteral administration involved absorption of drug via GI tract - includes oral, gastric, or duodenal (ex. feeding tube) and rectal administration - oral route is form of enteral administration and there are many ways that srugs can be administered orally

What are the essential nutrients for bacterial growth

Organic carbon (glucose, lactose, glycerol) --> for cellular macromolecules and structural components Water--> for cellular macromolecules and structural components Nitrogen (ammonia, amino acids)--> for nucleic acids and amino acids Phosphorus (inorganic PO4 or organic)--> for nucleic acids and phospholipids Oxygen--> for all cellular macromolecule (may say oh but obligate anaerobes cant use O2 but they do have O2 inside just not free O2) Sulfur (inorganic SO4 or organic)--> for amino acids (methionine and cysteine) and some vitamins Ions (Fe, Mg, Ca, Mn, Na, K, Cl)--> Most enzymes, transport

Describe the quantal dose response curve

Outcome is defined in advance - ex. zero virus detected - ex. drop of 10mmHg in blood pressure - ex. admitted to hospital Quantal: did individual have an outcome: yes or no? Frequency distribution curve- shows percent requiring dose to achieve desired effect Cumulative frequency distribution curve- shows cumulative percent exhibiting therapeutic effect ** can also do these for lethal does- precent req. dose for lethal effect and cumulative percent dead at each dose Lethal dose (LD) Toxic dose (TD) Effective dose (ED) If the chosen effect of drug is a lethal one, toxic one, or therapeutic one, the doses, which produce the effect in 1%, 50%, 99% of individuals, can be estimated from quantal log dose-response curve as follows: - Minimum dose: LD1, TD1, ED1 - Median dose: LD50, TD50, ED50 - Maximum dose: LD99, TD99, ED99 *LD50= dose that will kill 50% of those who take it *TD50= dose that will give a specific adverse effect in 50% of those who take it (usually most common or most problematic adverse effect)

Describe the outer membrane structure of bacteria

Outer membrane is found in gram-negatives and chlamydiaceae ONLY It is Asymmetric - Lipopolysaccharide (LPS) outer leaflet - Phospholipid inner leaflet Contains many proteins, including - Outer membrane porins (OMPs)- channels that allow things in and out of the cell Function of outer membrane: - Selective barrier - Protection against lysis - Impermeable to lage and/or aqueous molecules (protects against: lysozyme, cationic peptides, bile salts) ** NOTE: alot of gram negatives are found in the GI so they need protection against bile salts - Porins/transporters to let things through - Host mimicry and antigenic variation via sugars (O-antigen) and proteins O-Antigen - Lipid A is part of the O antigen (lipid A is the leading cause of sepsis/toxic shock in gram negatives) - E.coli outbreaks are designated by the O-Antigen and H-Antigen (which is flagella) **NOTE: D-Antigen is lipopolysaccharide

What is the main type of phase 1 reaction in the biotransformation (metabolism) of drugs?

Oxidation reactions - most important site of metabolism is the microsomal enzyme system (occurs in the liver) - reactions are catalyzed by microsomal enzymes (known as the mixed function oxidases (MFOs) or monooxygenases ***Most important= cytochrome p450 family of enzymes For Phase 2 reactions (ex. conjugation reactions) enzymes catalyze the conjugation of the substrate (the phase 1 product) with a second molecule - Glucuronidation (most common), sulfonation, acetylation, methylation, water conjugation, glutathione conjugation and glycine conjugation * Drugs that are polar may undergo conjugation directly without going through phase 1 If phase I metabolites are sufficiently polar, they may be readily excreted. However, many phase I products are not eliminated rapidly and undergo a subsequent reaction in which an endogenous substrate such as glucuronic acid, sulfuric acid, acetic acid, or an AA combines with the compound to form a highly polar conjugate - Such conjugation reactions are the hallmarks of phase II metabolism. A great variety of drugs undergo these sequential biotransformation reactions, although in some instances, the parent drug may already possess a functional group that may form a conugate directly

At rest one division of the ANS usually exercises dominant control over various organs (predominant tone)- the effects of ganglionic blockade can be predicted if you know division of the ANS is dominant at rest- What is the predominant tone (PT) - and what are the effects of ganglionic blockade?

PT : Sympathetic (adrenergic): Effects: - Arterioles--> vasodilation; increased peripheral blood flow; hypotension - Veins --> Dilation: peripheral pooling of blood; decreased venous return; decreased CO PT: Parasympathetic (cholinergic) Effects: - Heart --> Tachycardia - Iris--> Mydriasis (pupil dilation) - Ciliary muscle--> Cycloplegia- focus to far vision - GI tract--> Reduced tone and motility; constipation; decreases gastric and pancreatic secretions - Urinary bladder--> urinary retention - Salivary glands--> xerostomia (dry mouth) PT: Sympathetic (cholinergic) - Sweat glands--> Anhidrosis (absence of sweating)

Describe the Time vs. Drug Concentration (Cp) curve

Parameters used to compare the bioavailabilty of preparations: - peak height concentration (Cmax)- max drug concentration reached in plasma after administration of given dose - time of peak concentration (time of max drug conc. in the plasma) (Tmax) - area under the blood concentration time curve (AUC) Other useful parameters: - minimum effective concentration (MEC) - minimum toxic concentration (MTC) ** When giving a drug, it would be advisable to achieve a concentration which is "above" MEC but below MTC NOTE: for the same drug given in different dosgae forms, the rate and extent of drug absorption may vary Ex: intravenous injection, intraperitoneal or intramuscular injection, and oral administration

Observing & Reflecting Feelings

Paraphrasing vs. Reflectiong of Feelings Paraphrasing: - statements focus on the CONTENT of pts thoughts and behaviors Reflection of Feelings: - Focus on underlying emotion and help pt make his/her emotional life more explicit and clear - Identify key emotions of a pt and feed them back to clarify affective experience, brief acknowledgement of feeling may be more appropriate, often combined with paraphrasing and summarizing Predicted result: - Pts will more fully experience and understand their emotional state - Talk in more depth about feelings - Will enlarge interviewers reflection Purpose: - To get to "the heart of the matter"- underlying pts words, thoughts, and behaviors are feelings and emotions that motivate and drive action - goal is to be fully with the pt and increase width and depth of the interview using this skill Reflection of Meaning vs. Interpretation/Reframing Reflection of Meaning: - focuses on pts worldview - seeks to understand what motivates the pt - provides more clarity on values and deeper life meanings - gives pt more control of the healing process * interviews with this result in better understanding of pts Interpretation/Reframing: - results from interviewer observation - seeks new and more useful ways of thinking - *If pt does not respond to reflective strategies, move to active reframing or a theoretical interpretation * B4 this be sure you have heard the pts story NOTE: - 2/3 of all office visits to family phys are due to stress-related sxs - Many pts have mixed or ambivalent feelings toward their illnesses and the involvement of sig others - Use the reflecting skill to help pt sort out these complex feelings and thoughts - Found both phys & pt in basic experiece- there is a tendency in much interviewing to intellectualize and move away from deeper feelings and goals

Passive vs. Active Immunization

Passive: Involves injection of purified antibodies or antibody-containing serum (obtained from humans or occasionally horses) into a recipient - provides rapid, temporary immunity to an individual exposed to infectious agent or a toxin for whihch they lack active immunity - also helpful in immunocompromised pts who are unable to generate a natural immune response against the pathogen - protection from pathogen is TEMPORARY- it decreases when the immunoglobulins are cleared from the recipients serum over a few weeks to months ** Maternal antibodies that cross the placenta or are transferred in breast milk from mother to fetus= natural passive immunity Active: Recipients immune response is prompted to respond as if the body were experienceing infection with the microorganism (in case of natural, active immunication- the host really is experiencing the infection) - viable of non-viable organisms or purified products from the organism are used to stimulate the immune system and promote the development of prolonged immunity - Bc goal of active immunication is to promote the recipient to develop an immune response, it may take several weeks to months for the individual to develop immunity (unlike passive immunization where protection is immediate)

Describe the oxygen growth restrictions that bacteria have

Pathogenic microorganisms can tolerate different oxygen conditions Obligate aerobes: Need oxygen - Pseudomonas - Mycobacterium tuberculosis (pneumonia) - Bacillus (anthrax) Microaerophilic: Dont mind O2 - Campylobacter (GI disease) - Streptococci Facultative: aerobic & anaerobic (can grow anywhere) - E. coli (GI, UTI) Obligate anaerobe: free atm oxygen is damaging - Clostridium (deep wound, food poisoning) ** In tubes of liquid medis the further down, O2 dissipates

MOA of Fluoroquinolones (Ciprofloxacin, Levofloxacin, Moxifloxican)

Penetration through the cell envelope by diffusion through the aqueous channels of the outer bacterial membrane Inhibition of the bacterial DNA function by: 1. Blocking topoisomerase II (also called DNA gyrase)- The blockade prevent the relaxation of supercoild DNA which is required for normal transcription (prevalent mechanism in gram-negative bacteria) 2. Blocking topoisomerase IV- the blockage interferes with seperation of replicated chromosomal DNA during cell division (prevalent mechanism in gram-posiitive bacteria) Ultimate effect is: BACTERICIDAL - bacterial killing is concentration-dependent (increasing concentrations kill and increasing proportion of bacteria and at more rapid rate) - a significant postantibiotic effect is present (antibacterial activity persists several hrs beyond the time that measurable drug is present)

Antibiotics that inhibit the bacterial cell wall

Peniclilins: - penicllin - amoxicillin/ampicillin - oxacillin/nafcillin/dicloxacillin - piperacillin Cephalosporins: - Cefazolin/cephalexin - Cefuroxime/Cefotetan - Ceftriaxone/Cefotaxime/Ceftazidime - Cefepime - Ceftaroline Carbapenems: - Imipenem-Cillistatin - Meropenem - Doripenem - Ertapenem Monobactam: - Aztreonam Vancomycin Other: - Fosfomycin - Daptomycin ***Beta-lactamase inhibitors= Calvulanate, Sulbactam, Tazobactam

The enduring inner characteristics of individuals that organize behavior is referred to as

Personality - enduring over time - consistent across situations - mediates relationship with the world - seeks and creates meaning The Psyche: - Id: biologically-based instincts (sex and aggression) - Superego: socially-prescribed standards (parents, religion, law) - Ego: the manager (formed by nature and nurture and favors characteristic defenses) Conflight: Should I work late with an attractive colleague?

Differentiate between pharmacological, immunological and cytotoxic side effects

Pharamcological (80% of cases): resulting from one or more of the specific effects of the drug or of its metabolites ** most of these can be predicted, by understanding the MOA of the drug - reducing drug dosage may be sufficient to avoid the side effects Ex: Excessive bleeding caused by an anticoagulant Cytotoxic (~10%): drug causes cell damage Ex: Liver injury caused by acetaminophen overdose Immunological (~10%): drug has activated the immune system Ex: Penicillin allergy

List the phases of peptidoglycan cell wall synthesis and antibiotics that inhibit the steps

Phase 1: monomer production - Synthesis of UDP-acetylmuramoyl-pentapeptide ** Fosfomycin inhibits enolpyruvate transferase Phase 2: addition of a bridge peptide, if present - Addition of a dipeptide to the UDP-acetylmuramyl-pentapaptide **Cycloserine inhibits enzymes involved in the synthesis of the dipeptide Phase 3: monomer translocation and transglycosylation - The new monomer is incoporated into the growing strand of peptidoglycan molecule ** Vancomycin inhibits transglycosylase Phase 4: transpeptidation - Single strands are cross linked ** Beta-lactam drugs inhibit transpeptidases --------------- Cell Wall inhibition in gram-positive and gram-negative cell walls: 1st: fosfomycin 3rd: vancomycin 4th: beta-lactams

What are the phases of PG biosynthesis

Phase I: Monomer Production: - PG is built from the polymerization of PG monomers, which are comprised of NAG-NAM-peptide tail - Monomer production occurs in the cytoplasm - The Monomer is completes on bactoprenol-P (aka undecaprenol-P, C55-P--> this scaffold is used for production of many extracellular polysaccharides) ** Bacterial cell uses bactoprenol-P and then recycles it because it is very difficult to make Phase II: Bridge peptide (if present) - IF a bridge peptide is present, it is added in phase II - S. aureus has a pentaglycine bridge, other species can have others - Many bacteria DONT have a bridge ** Bridge peptide is not needed its just a decoration Phase III: Translocation and Transglycosylation * Where the action really starts to happen - The completed monomer is translocated across the PM - Transglycosylases (a transpeptidase) incorporate the new monomer into the PG macromolecules - The bactoprenol-PP is recycled (very expensive molecule) Phase IV: Transpeptidation - Transpeptidases cross-link strands through peptide tails/bridges - The final D-ala is cleaved by the transpeptidase to provide energy to the reaction - Cross-linking is not complete- some tails remain unlinked (this is fine bc PG is always a work in progress)

Catecholamines and derivatives are markers for

Pheochromocytoma

What are some factors affecting oral drug absorption?

Physiochemical factors: molecular size, oil/water partition coefficient, polymorphism, etc. Formulation factors: disintegration, dissolution rate, diff excipients, etc. Physiological factors: gastric emptying, pH, kind of GI content, intestinal motility, blood flow and secretions, first-pass loss, enterhepatic cycle Clinical factors: surgical operations (gastrectomy, vagotomy, intestinal shunts), diseases (ulcerative colitis, Crohns disease, etc.) pharmacological interactions Drug absorption by oral route: The small intestine, particularly duodenum area, is MOST IMPORTANT site for passive drug absorption due to its: - high surface area and high blood flow - SI transit time randes from 3-4hrs for most healthy persons - If absorption is NOT completed by time a drug leaves the small intesting, absorption may be erratic or incomplete Absorption pattern: variable (affected by many factors) Advantages: - safest and most common - convenient and economical Disadvantages: - limited absorption of some drugs - food may affect absorption - pt compliance is necessary - drugs may be metabolized before systemic absorption

Natural Alkaloids

Pilocarpine MOA: activation of M1, M2, M3 receptors Pharmacological effects: - peripheral effects are very similar to those of choline esters- stimulation of salivation and sweating is particularly prominent - central effects include arousal, excitation, headache and tremores (Pilocarpine enters the CNS) Clinical uses: - Treatment of xerostoma: dry mouth due to radiation treatment for cancer, or Sjogren Syndrome - Treatment of glaucoma - Induce miosis Adverse effects (mostly predictable): - Most adverse effects are very similar to those of choline esters - Diaphoresis (profuse sweating) is the most common adverse effect Muscarine - historical and research significance but not used clinically. Muscarinic receptors are named after muscarine - found in some types of mushrooms that grow in North America ** Muscarine Poisoning--> Increase muscarinic receptor stimulation--> Decreased HR, BP, lungs fill with fluid, hard to breath - incontinent for uring and feces

Differentiate between Placebo and "Nocebo"

Placebo: any substance whose beneficial effects are attributable to its use, but not to its specific pharamacodynamic properites - On avg. 35% of benefit of drug is placebo effect - Influeced by many factors.. Ex. physician attitude, environment of drug use, size/color/taste of medicine "Nocebo": any substance whose harmful effects are attributable to its use, but not to its specific pharamacodynamic properities - Ex: reading the side effects of statins drugs and psychologically thinking you have them- while physiologically you do not

Conjugation

Plasmid mediated exchange of information between bacteria in contact Process: free plasmid moves from donor to recipient cell via sex (F) pilus and then the integrated plasmid (episome) promotes transfer of genomic DNA, which integrates into recipient DNA F+ and F- Conjugation: - Cell-to-cell transfer of DNA from on bacterium (male/DONOR) to another (female/RECIPIENT) - DIRECT cell-cell contact - One direction: Male--> Female - Males (DONORS) need conjugative F plasmid (fertility plasmid (F+) encoding fertility factor - Transfer occurs via unique pilus: sex pilus=bridge=F-pilus - F-pilus encoded by tra operon on the F plasmid - Sex pilus= Type IV secretion system ** Eventually all cells become F+

Tissue Sporozoa

Plasmodium spp. (blood & tissue)--> malaria Babesia spp. (blood)--> babesiosis Toxoplasma gondii (tissue)--> toxoplasmosis ---- Sporozoa: two life cycle, two hosts Sexual (sporogony): definitive host Asexual (schizogony): intermediate host

Bacterial polymerases can be exploited to diagnose infectious disease- can you give an example of this?

Polymerase Chain Reaction (PCR) uses heat stable DNA polymerases to amplify DNA sequences - Taq polymerase Allows for: - species or strains to be identified - identify drug resistance - rapid!

Carbapenem-resistant Enterobacteriaceae (AKA CRE)

Possesses NDM-1, an enzyme which allows them to cleave carbapenems, one of the most powerful types of antibiotics available to doctors - New Delhi metallo-beta-lactamase-1 ** Nightmare Scenario: - Gene for NDM-1 can be transferred to a bacterium that is resistant to all other antibiotics. ex. VISA, VRSA (vancomycin resistance) *** At least one NDM-1 bacterium has been found that is resistant to all known antibiotic

List the stages of the Transtheoretical Model of Change

Pre-contemplation - person is NOT even considering changing- they may be "in denial" about their health problem, or not consider it serious. they may have tried unsuccessfully to chang so many times that they have given up **** Educate them on risk vs. benefits and positive outcomes related to change--> guide pt to "contemplation"**** Contemplation - person is ambivalent about changing- during this stage, the person weighs benefits vs costs or barrier (ex. time, expense, bother, fear) **** Identify barriers and misconceptions, address concerns, identify support systems, and guide pt to "preparation**** Preparation - the person is prepared to experiment with small changes ****Develop realistic goals and timeline for change, provide positive reinforcement, and guide pt to "action"**** Action - the person takes definitive action to change behavior **** Provide positive reinforcement--> guide pt to "maintenance"**** Maintenance & Relapse Prevention - person strives to maintain the new behavior over the long term **** Provide encouragement and support and provide positive reinforcement**** Stages of change are useful for physicians bc it allows for: - more realistic expectations - greater recognition of small accomplishments - greater success over time - less frustration and burn-out - increases resilience

Precipitation test

Precipitation occurs when the antigen is soluble. - Many precipitation-based technques are available for the detection and/or quantitation of antigen or antibody - These are based on the binding of antibody to specific antigen, or the reverse, and the formation of a conjugate - It is usually possible to demonstrate the presence of the conjugate in the form of precipitation * these reactions depend on the interaction between optimal quantities of antigen and antibody Presence of excessive amounts of antigen or antibody results in inadequate cross-linking and the formation of lower amounts of immune complexes or precipitate - In practice, this may result in the appearance of a false negative reation, in the presence of both antigen and antibody - In a system where the amount of antibody is kept constant, as shown below, the presence of very small amount of antigen results in less precipitation due to the prozone phenomenon - Presence of excess antigen would also result in less precipitation due to the postzone phenomenon - Only in the equivalence zone, where antigen and antibody are mixed in the best proportion, is maximal precipitation acheived - Thus, serologic reactions may give false negative results if the reactants are mixed disproportionately

Precursor lesions as predisposing to cancer

Precursore lesions: localized morphologic changes associated with a high risk of cancer - usually in epithelial surfaces - NO mandatory progression to cancer Ex: - Metaplasia: Barrett esophagus, leukoplakia, and colonic metaplasia of gastric mucosa - Hyperplasia: endometrial - Dysplasia and Ca in situ: uterine cervix, vulva, etc - Benign tumors: villous adenoma of the colon **** A vast majority of benign tumors has a minimal risk of malignant transformation

Phases of the Life Span

Prenatal (Conception to birth) - rapid development of NS Newborn stage and infancy (Birth to 12 months) - Motor development, attachment and bonding Childhood (12months-12yrs) - development of logical thinking Adolescence (12-18yrs) - abstract thinking, formation of identitiy, peer influence Adulthood (18-60) - love, marriage, career stability Senior yrs (60-death) - Decrease in physical ability, reflection on life, preparation for death

Differntiate between Presynaptic and Postsynaptic Regulation

Presynaptic regulation - Transmitter release can be inhibited or facilitated by the activation of receptors on the nerve terminal - When the receptor on the presynaptic nerve regulates the release of the transmitter that activates it; it is called an autoreceptor - The most significant autoreceptor that contributes to drug action is the alpha 2 receptor- when NE binds to the alpha2 receptor on adrenergic neurons, this result is decreased NE release - When the receptor on the presynaptic nerve regulates the release of a transmitter other than the one that activates it, it is called a heteroreceptor Postsynaptic Regulation - When receptors are chronically activated, down regulation (aka desensitization or refractoriness) of those receptors may occur Mechanisms of down regulation: - destruction of receptors - decreased syn of receptors - attenuation of signal from stimulated receptors When receptors are chronically inhibited, up-regulation (aka sensitization or supersensitivity) of those receptors may occur. Denervation super-sensitivity is an extreme form of up-regulation Mechanisms of up-regulation: - increased syn. of receptors - loss of mechanism or NT removal - increase pot-junctional responsiveness

Purpose of Infection control is to

Prevent & Reduce Most common types of adverse events in healthcare include: - HCA (Healthcare acquired or associated)= infection acquired furing the provision of healthcare, most definitions do not include hospital - HAI (Hospital-associated/acquired infection)= nosocomial infection appears >/- 48h after hospital admission or <48h after discharge - CA= community-acquired infection - Iatrogenic= infection caused by physician (includes healthcate measures in general) - Others' ex. HACO (healthcare-associated community-onset), HO (hospital-onset) infections

What is Decontamination and the 3 processes it involves?

Prevents microorganisms reaching a susceptible site in sufficient numbers to initiate infection 3 Processes: 1. Sterilization - Destruction of all living thinds and viruses- cant be "mostly sterile" - CANNOT be achieved on live tissue, is used for fomites (equipment and surfaces, liquids, etc.) 4 major types: a. Heat: autoclaving, baking b. Irradiation: commercially, maintains protein structure c. Filtration: delicate chemicals or equipment, air d. Chemical: sensitive equipment, large objects or areas 2. Disinfection - Destruction/inactivation of MOST viable organisms: is result good enough? Killing 99.99% of a billion bacteria isnt as impressive as it sounds - Many will not kill spores or certain classes of bacteria or viruses - Sometimes called "germicide" - Broken into levels * There are high, intermediate and low level disinfectants 3. Cleaning

Dissemination of Viruses in the Body

Primarily through the bloodstream and lymphatic system (viremia) - Often, replication in macrophages, endothelial cells, and the liver helps amplify the virus and initiate a secondary viremia for the infection of target tissues leading to the manifestation of characteristic symptoms - Entry into the CNS occurs from the blood, infected meninges or cerebrospinal fluid, infected leukocytes, and infected peripheral or sensory neurons

List the steps from Lab result to treatment

Primary prophylaxis --(infection suspected: obtain samples for microbiologic analysis)--> Empiric treatment ---(24-48hrs: preliminary and interim microbiology results available (ex. gram stain))--> Targeted treatment --(24-48hrs: final microbiology results available)--> Definitive treatment --(days-months "cure")--> secondary prophylaxis --> weeks to years

Temporal approach to Infectious Disease therapy

Primary prophylaxis --- (infection suspected; obtain samples for microbiologic analysis)---> Empiric treatment ---(24-48hrs: preliminary and interim microbio result available ie. Gram stain)---> Targeted treatment-- (24-48 hrs: final microbio result availabile)---> Definitive treatment -- (Days-months- "Cure")---> Secondary prophylaxis (weeks to yrs)

What are Prions?

Prions (PrPC or PrPSC) are noncellular, infectious proteins - Human cells make a normal protein (PrPC) encoded by the PRNP gene - Mutations in PRNP result in an abnormally shaped protein, PrPSC - PrPSC converts PrPC into more PrPSC - The abnormal protein (PrPSC) accumulates and forms clumps that damage/destroy neurons creating microscopic sponge-like holes Outcome--> Neurologic Disease (Spongiform Encephalopathies- MadCow dieases --> brain death)

Stages of Viral Disease Include

Prodromal phase and the "Symptomatic" phase **Incubation period can be asymptomatic, or can present as a set of early, nonspecific sxs referred to as the prodrome Prodromal phase: - Non-specific systemic symptoms --> Innate immunity --> IL-1, IL-6, TNF-alpha, IFN-alpha/beta, IFN-gamma Symptomatic phase: - Cytolysis & Cytopathic effects - Cell-mediated immunity--> TH1 (IFN-gamma), Aberrant TH2 - Antibody response--> IL-4 or IL-17 or IFN-gamma BOTH direct viral involvement and acquired immunity will contribute to disease **Specific tissue involvement making the infection identifiabl as a resp. infection, or a CNS infection etc.

Benign Prostatic Hyperplasia (BPH)

Produces symptomatic urethral obstruction that leads to weak stream, increased urinary frequency and waking during the night bc of the need to urinate (symptoms can be a mix of urinary incontinence and urinary retention- bc alpha1 in prostate makes it harder to empty the bladder) The sxs are caused by increased smooth muscle tone in the prostate and the neck of the bladder How would you target the sympathetic nervous system to treat the disease? block alpha1 --> may lead to decreased BP (side effect- this could be helpful for ppl with high BP) - especially orthostatic HTN blood pulling bc blood vessels dont consrict- so when you stand up you are dizzy and have an increased fall risk (especially in older men)

Tumor Antigens

Products of mutated genes (ex. RAS or p53) Over-expressed or aberrantly expressed cellular proteins ex. tyrosinase in melanomas Products of oncogenic viruses ex. E6 and E7 of HPV Normally expressed cell-type-specific differentiation antigens, ex. CD20 (a potential target for immunotherapy)

Describe virus self-assembly

Protein/polyprotein and nucleic acid synthesis --> Assembly of increasingly complex structural subunits (protomers and capsomers)--> Transport of structural subunits & nucleic acids to appropriate cellular compartments --> Capsid or nucleocapsid assembly, viral protein insertion in host lipid membranes --> Nucleic acid and accessory protein insertion --> Acquisition of an envelope NOTE: There is variation in order, some viruses dont need some steps (ex. naked viruses will NOT acquire an envelope) - Random, many errors (high proportion of VLPs)

Electronic Medical Records

Provide quality and convenience and privary and security Most commone EMR= Epic Dont forget your communication skills if using EMR: - introduce yourself - establish rapport - open-ended questions at beginning - maintain good eye contact - be supportive and concerned - use transitional statements - avoid medical jargon - allow pt to speak without interruption - summarize history - give pt a change to ask questions - appear poised, professional, confident ** remmeber doctor who told pt she was going to be typing and asked if pt would like to look at computer together

Pseudoallergic vs. Anaphylactoid

Pseudoallergic: drug administration provokes typeI allergic reaction but circulating antibodies cannot be detected - clinical sxs are due mostly to direct release of histamine and other mediators caused by the drug - drugs such as opiods, some antibiotics (vancomycin), curare-like drugs, some plasma expanders (dextran) and some contrast media are among drugs able to directly release histamine from mast cells and basophils- unlike for true anaphylaxis, these drugs are dose-dependent in most cases- and they are not true drug allergies so the medications are not contraindicated for future use by the pt Anaphylactoid: most like anaphylaxis

After a gram stain you find that the bacteria is a gram-negative bacilli with straight rods and aerobic (non-fermenter) that is oxidase positive- what bacteria may it be

Pseudomonas sp. or Legionella sp. Pseudomonas sp. - Beige on MacConkey - Resists cetrimide - Produces pyocyanin - multi-drug resistant - can grow anaerobically with alternat electron acceptors Legionella sp. - thin, short or long - gram stain poorly - dieterle silver stain - direct flurescent antibody test (DFA) - BCYE agar + cysteine, iron - 3-5 day incubation

What are terms that describe the temperature and pH growth restrictions of bacteria?

Psychrophiles (some pathogens)- 0-23*C (Listerominonitogenes can grow in refridgerator) Mesophiles (most pathogens (37*C)- internal body temp these are ones that MOST effect humans Thermophiles (NO pathogens)- deep sea hydrothermal vents we die at these temps so not pathogenic to us Acidophiles (few pathogens): pH~2 in GI and uterus Neutrophiles (most pathogens): pH~7 (most in our body) Alkalinophiles (few pathogens): some parts of our body are alkaline

Complement Fixation Test

Pt serum is heated to destroy complement - specific antigen and measured complement are then added to pts serum - after appropriate incubation, sheep RBCS are added - if any antibody in pt serum has activated complement, complement hemolytic activity will be depleted and there will be no lysis of sensitized sheep RBCs - if there is no antibody in pt serum, sheep RBCs will be lysed ** thus, the test demonstrates presence of specific antibody in serum Ab present, (positive test), complement fixed --> no lysis of indicator cells Ab absent, (negative test), complement not fixed --> lysis of indicator cells NOTE: this is a - lab test to determine if pt has antibody to specific antigen - does NOT measure complement - uses complement mediated lysis of sensitized RBC as indicator system - employs fact that complement is heat sensitive to get rid of pts complement so that known amt of complement can be added - complement decreases (is consumed) when specific antibody binds to antigen and activates complement

Adjuvants

Purified antigens such as proteins are often not immunogenic on their own- IN order for an immune response to be induced against an acellular antigen, often an adjuvant, or a substance that enhances the immunogenicity of antigens, must be used - Adjuvants are thought to stimulate antigen presenting cells (particularly dendritic cells) so they can present antigens and express cytokines and co-stimulatory molecules to effectively stimulate antigen-specific T cells - they also slow down release of antigen to help sustain the immune response long enough for effective immunity to develop 4 Adjuvants currently in use in US: 1. Aluminum salts and aluminum gels (most adjuvanted vaccines such as aluminum hydroxide, aluminum phosphate, and aluminum potassium sulfate 2. M529, an oil-in-water emulsion of squalene oil 3. CpG 1018, an adjuvant based on synthetic DNA sequences 4. AS01B which is made of up monophosphoryl lipid A (MPL), a purified fat-like substance, and QS-21 which is purified from the back of the Quillaja saponaria (soap bark), an evergreen tree native to central Chile - The only adjuvants currently in use in Canada are aluminum salts and toxoids- all these adjuvants have been demonstrated to be safe Aluminum slats are substances used in clinical practice as adjuvants- Ex: tetanus toxois alone is not immunogenic so the tetanus toxoid vaccines contain aluminum slats which bind polyvalently to the toxoid and sitmulate antibody responses - Furthermore, the pertussis toxoid and the diphtheria toxoid can be used as adjuvants themselves- the diphetheria toxoid is the most common adjuvant for polysaccharide conjugate vaccines

Appendix with larger hyperemic blood vessles and increased neutrophils in tunica muscularis and polymorphonuclear leukocytes. DX?

Purulent appendicitis

A pt presents 10 days of malaise with vague aches and pains and 2 days of pain in his chest and severe head ache- when admitted to hospital there was neck stiffness and papilledema - CSF reveals high protein content and numerous neutrophils- the pt most likely has

Purulent meningitis

Cell Cycle Inhibitors

RB protein--> inhibits E2F *p16 (p16/INK4A)--> inhibits Cyclin D/CDK4- mediated phosphorylation of RB protein *p14/ARF--> increases level of p53 (which activates p21) p53--> activates p21, GADD45, and BAX p21 (CDKN1A) inhibits cyclina E/CDK2 **** BOTH p16/INK4A and p14/ARF genes are located in CDKN2A locus in chr. 9p - these are regularly mutated in cancer on chromosome 9 (CDKN2A--- is the locus that contains 2 genes: p16 & p14)

Examples of G-protein coupled receptors

Receptor types: Beta-2, D1, H2 - Gs - effector: increases adenylyl cyclase - second messenger response: increased cAMP Alpha-2, D-2, mu opiod - Gi - effector: inhibits adenylyl cyclase - second messenger response: decreased cAMP M1, M3, Alpha-1 - Gq - effector: activates phospholipase C - second messenger response: increases IP3/DAG

Receptor binding curve

Receptors bound (% max) vs. epinephrine concentration (nM) on logarithmic scale--> still yields sigmoidal curve New values: Bmax= Max amount of receptors bound KD= concentration of epinephrine needed to bind 50% of receptors *** EC50 < KD (the max effect of receptor can be reacted without binding all available receptors) BUT For many drugs KD > EC50, Why? Full agonist can produce maximum effect (Emax) without binding all receptors--> leaving "spare" receptors (i.e. cells contain 1000 Beta2 receptors/cell to get max cAMP only need to bind 100 receptors so on every cell there will be 900 spare receptors

Baroreceptor Reflex

Regulates arterial BP - The response is fast; usually occurs within seconds or minutes - Baroreceptors respond to stretch and pressure- they are located in the wall of the carotid sinus as well as the wall of the aortic arch - When the arterial BP falls, there is an increase in symp stimulation and a reduction in parasympathetic activity- the result is an increase in HR, cardiac contractility and vascular resistance. Venous vasoconstrictions is also increased which increases venous return and cardiac output - When arterial BP rises, there is a reduction symp activity and an increase in parasymp activity- this results in decreased HR, contractility and vascular resistance

What are the routes of drug excretion?

Renal: MOST IMPORTANT! Intestinal: biliary excretion, fecal elimination Pulmonary: for gases or volatile drugs Others: breast milk, saliva, sweat, tears, nasopharyngeal secretions Renal excretion occurs by: - glomerular filtration - tubular secretion - tubular reabsorption Urinary Excretion of Solute= Filtered Load - Reabsorption by Tubules + Secretion by Tubules *** The rate at which kidneys excrete solute into urine= rate at which solute disappears from blood plasma

What occurs in gene amplification?

Replicating chromosome undergoes homologous recombination (2 matching sequence of DNA interact incorrectly giving): - Cell A (with two copies of gene X) - Cell B (with no copies of gene X) If there is selection of bacteria which require gene X for growth or pathogenesis - Then there will be selection for strains with multiple copies of gene X Ex: amplification of ctx locus (gene for Vibrio cholerae cholera toxin) - locus with this toxin amplifies itself --> strains of vibreou cholera that cause disease cholera --> increase diarrhea would immob. pt--> Pt wont be able to move but latter ppl go in water diarrhea get in food washing and clothes--> increasing spread Ex: Pilin protein of N. gonorrhoeae - Mechanism of antigenic variation for N. gonorrhoeae pilin. Antigenic variation occurs via homologous recombination between the expressed locus (pilE) and silent locus (pilS) - This recombination makes new pilin protein (theoretically over a million different pilin subunits)

Common defenses among pts

Repression - blocking from awareness, "motivated forgetting" Denial - refusing to believe or experience the impact of external events Undoing - "erasing an unacceptable event in the past by adopting acceptable behavior in the present (superstitious behavior) or by atonement or confession Regression - Reverting to childlike behavior when under stress - Common among hospitalized pts (i.e pt who wants to be sung a lullaby even though 39 yo) Idealization

Describe Culture-Based Testing

Requires VIABLE organisms and ability to PROPAGATE (media and conditions) - Slow - Usually followed up by further investifation to ID what has grown (biochemical tests, typing (genotype, phage, etc.), antimicrobial susceptibility testing When is culture useful? - Best for bacteria or fungi that grow readily and are easily identified - Usually necessary for antimicrobial susceptibility testing - Avoid culture when: Agent is extremely infectious and agent causes disease with NO CURE Culture media: - General, relatively non-selective - Blood agar is lab "worksheep"- practically everything is put on blood agar - differential medium * its specific for some organisms- can give huge clue as to causative agent: - provide specific nutrients - prevent growth of most organisms - presence of a particular biochemical pathway

Atropine

Route of administration: IM, IV, IO (intraosseous), SubQ, ophthalmic and endotracheal MOA: Inhibition of muscarinic receptors Clinical uses: - Antidote for anticholinesterase poisoning - Antidote for muscarine-containing mushrooms poisoning - Adjuvant use with anticholinesterases (ex. neostigmine) to decrease their adverse effects during neuromuscular blockade reversal - Induce mydriases and/or cycloplegia - Treatment of acute symptomatic bradycardia - Aspiration prophylaxis (due to excessive salivation)

Dobutamine

Route of administration: IV MOA: - Selective Beta1 agonist Pharmacologic effects: - More prominent inotropic than chronotropic effects- Increases contractility and cardiac output but little or no change in heart rate Clinical uses: Short term management of cardiac decompensation (when heart not beating hard enough) Ex: - pts after cardiac surgery - congestive heart failure - acute MI Adverse effects: - Blood pressure and HR may increase significantly, pressor response may be exaggerated in pts with history of hypertension

Isoproterenol

Route of administration: IV MOA: Nonselective Beta agonist; Beta1 and Beta2 Pharamacologic effects: - lowers peripheral vascular resistance and diastolic pressure (beta2) - systolic BP is unchanged or slightly increased (beta1) - MAP usually decreases - Positive inotrope (increases cardiac contractility) and chronotrope (increase HR); cardiac output is increased. Effects from direct action of the drug and reflex action in response to decreased peripheral resistance - Bronchodilation (not used for resp. disease bc of the actions on the heart, the selective beta2 agonists are preferred) Clincal uses: - bradycardia - Torsades de pointes - Temporary control of bradycardia in denervated heart transplant pts who are unresponsive to atropine - ventricular arrhythmias due to AV nodal block - beta blocker overdose Adverse effects: - Tachycardia, ventricular arrhythmia, hypokalemia, increased serum glucose, tremor, headaches, and seizure Contraindications: - Angina, preexisting ventricular arrhythmia, tachyarrhythmia

Dopamine

Route of administration: IV - Rapidly metabolized by catechol-o-methyltransferase (COMT) and monoamine oxidase (MAO) in the liver and adrenergic neuron - Does NOT cross BBB MOA: - activation of dopamine D1 and adrenergic receptors (mostly beta1) Pharmacologic effects: - Low dose: vasodilation in renal, mesenteric and coronary beds (D1). Increased glomerular filtration rate and Na+ excretion - Intermediate dose: increased stroke volume and heart rate (beta1) - High dose: Increased systemic vascular resistance, splanchnic and renal blood flow decrease (alpha1) Clinical uses: - Heart failure (beta1), especially in pts with oliguria (low urine production) and low or nml peripheral resistance - Adjunct treatment of shock after fluid replacement (cardiogenic shock & spesis- NE is preferred) Adverse effects: most predictable based on sympathomimetic actions - tachycardia, angina, hypertension and arrhythmias

Norepinephrine

Route of administration: IV - Rapidly metabolized by catechol-o-methyltransferase (COMT) and monoamine oxidase (MAO) in the liver and adrenergic neuron - Does NOT cross the BBB MOA: - Agonist at alpha1, alpha2, and beta1 receptors (No beta2, accounts for the difference in pharmacologic effects compared to epinephrine) Cardiovascular Effects: - Systolic pressure increases (alpha1, beta1) - Diastolic pressure increases (alpha1) - CO is unchanged or decreases (reflex cancels out direct effect) - Peripheral resistance increases (alpha1) - HR decreases due to baroreceptor reflex, overrides the direct beta1 effect Clincal uses: - Hypotension/shock (**FIRST choice drug for the treatment of cardiogenic shock and septic shock) Adverse effects: - Similar to epinephrine (but no beta2 effects), however greater elevation in BP - Bradycardia (reflex) - Reduced blood flow to kidney and intestines (bc of vasoconstriction-alpha1) Contraindications: - Similar to those for epinephrine (except for beta2 effects)

Epinephrine

Route of administration: IV, IM, SubQ, inhalation, endotracheal and topical - Rapidly metabolized by catechol-o-methyltransferase (COMT) and monoamine oxidase (MAO) in the liver and adrenergic neuron - DOES NOT cross the blood brain barrier (remember alpha2 mostly CNS) MOA: - Agonist at alpha1, alpha2, beta1 and beta2 receptors - At low concentrations epinephrine has predominantly beta1 and beta2 effects- at higher concentrations alpha1 effects become more pronounced Pharmacological effects: - SA node: increases heart rate (beta1) - AV node: increas in automaticity and conduction, decrease in refractoriness (beta1) - Atria and ventricles: increase in automaticity, conduction and contractility and decrease in refractoriness (beta1) - Cardiac efficiency: work done relative to oxygen consumption is decreased (beta1) - Cardiac systole is shorter and more powerful, cardiac output is enhanced (beta1) - Vessels: vasoconstriction in cutaneous, GI and renal vessels (alpha1), vasodilation of skeletal muscles (beta2), coronary and pulmonary vessels (autoregulation overrides direct vasoconstricot effect) - GI tract: relaxation - Bladder: relaces the detrusor muscle (beta3), constriction of internal sphincter (alpha1) - Respiratory: bronchodilator (beta2) Metabolic: - inhibits the secretion of insulin (alpha2); increases insulin secretion(beta2)- the predominant effect on insulin secretion is inhibition - Elevates glucose and lactate in blood - Stimulation of glycogenolysis and gluconeogenesis - Increase plasma free fatty acids (beta stimulation in adipocytes) - Eye: Mydriasis (alpha1)

Albuterol and Terbutaline

Route of administration: IV, oral and inhalational MOA: - Selective Beta2 agonist *** Pharmacologic effects: - Relax bronchial smooth muscle and decrease airway resistance - Suppress the release of leukotrienes and histamine from mast cells - Enhance mucociliary fx and decrease microvascular permeability - Increases uptake of K+ by skeletal muscle *** Clinical Uses: (**these are indications for Beta2 drugs) - Bronchospasm - Hyperkalemia Adverse effects: - Tremor (due to CNS and skeletal muscle effects) - Tachycardia (when given by IV, due to nonselective beta1 receptor activation), reflex action due to reduced peripheral resistance caused by vasodilation of skeletal muscle - Excitement/nervousness- beta receptor activation in the CNS Contraindications/Precautions: - Glaucoma: may increase intraocular pressure - Diabetes: may increase serum glucose, lactate and free fatty acids - Hypokalemia: especially important in pt with cardiac disease - Seizures (bc of CNS excitability)

Apraclonidine

Route of administration: Ophthalmic - DOES NOT cross the BBB (unlike clonidine)- so apraclonidine has NO CNS effects MOA: - Selective alpha2 agonist Pharmacological effect: - Decrease in aqueous humor production (alpha 2 agonist- decreases aqueous humor) Clinical use: - reduction of intraocular pressure

Prazosin

Route of administration: Oral MOA: Competitive inhibition of alpha1 receptors Effect: - Relaxes arterial and venous vascular smooth muscle (decreases preload and afterload) - Reflex tachycardia in response to the drop in BP is usually less than would be predicted. This may be due to CNS effects that block the barreceptor reflex - Relaxes smooth muscle in the prostate Clinical Uses: - Hypertension (NOT a first choice drug) - BPH- Benign Prostatic Hyperplasia (*Tamsulosin is first choice drug) - Raynaud disease Adverse effects: - ** Orthostatic hypotension/syncope (fainting)- most significant when therapy is first started or when combined with other antihypertensive drugs or a phosphodiesterase 5 (PDE5) inhibitor - Nasal congestion - Miosis - Priapism- prolonged erections

Clonidine

Route of administration: oral, epidural, transdermal patch MOA: Selective alpha2 agonist (in CNS- decreases symp and BP) Pharmacological effect: - hypotension at low doses (CNS alpha2 receptors)- therapeutic target - hypertension at very high doses (peripheral alpha2 receptor) Clinical Uses: - Hypertension (bc it lowers BP) - Pain management Adverse effects: - Drowsiness, fatigue and headache - Xerostomia (dry mouth)- alpha2 decreases water secretion

Non-lactose fermenting Enterobacteriaceae that are Non-H2S producing

Shigella: - Non-motile - 4 species, limited to colon Yersinia - Short, pleomorphic gram-negative rod (coccobacillus) - bipolar staining ("safety-pin") - growth in 48h - Y. enterocolitica (enterocolitis)--> urease +, motile at 25*C, not higher , can grow slowly at 4*C - Y. pestis (plague)--> urease -, non-motile "SY to SYPS in CEEK SYPS"

What are sigma factors?

Sigma factors activate transcription - Bacteria: polypeptide unit= sigma factor necessary for recognition of promoter - they DO NOT bind to promoter but bind RNApol - increase affinity/specificity of RNApol for promoter - different sigma factors recognize diff promoters - production of alternate sigma factor regulated by environment, allows expression of specific genes Usually there is one major sigma factor commonly used but there are many Specialized sigma factors allow binding to sepcific, atypical promoters: - Transcription of specific genes when needed - Sigma 28 req for flagellar genes (escherichia) - Sigma E, F, G, H for sporulation genes (bacillus) - Sigma B expressed under stress (staphylococcus) NOTE: - Anti-sigma factors PREVENT interaction of particular sigma with RNApol

Fishers Exact Test

Similar to Chi-square, used for nominal/categorical data and determines whether observed differnces in proportions between study groups are statistically significant - used for very small sample sizes (n<25) - primarily used for researching rare diseases

Describe the replication of single-stranged DNA viruses

Similar to replication of dsDNA viruses BUT - DNA-dep RNApol CANNOT bind ssDNA, so the incoming viral ssDNA must first have its complementary strand synthesized by DNA-dep DNA pol (which can bind either ssDNA or dsDNA) before any transcription can occur - These req. hairpin structures (palindromic sequences) functioning as primers for the DNA-dep DNApol - There is only 1 virus of medical importance that does this --> the Erythrovirus (Parvovirus B19; Parvoviridae) responsible for erythema infectiosum (aka fifth disease or slapped-cheek disease, a common childhood infection

Compare and contrast fungi to human cells

Similarities: - Fungal cells have eukaryotic internal structures like mitochondria, golgi apparatus, chromosomes, etc. and protein synthesis similar to humans. Both use organic compounds Differences: - Fungi have cell walls: complex carbohydrates: chitin with glucan and manoose-proteins; the cell wall glucan (not found in humans) is now an antigunfal target of the echinocandins. Zymosan (protein-carbohydate) triggers immune system. - Fungi have ergosterol as the major membrane (plasmalemma) sterol; target for azoles and polyene antifungals

DNA Damage and Repair

Single Strand Break --> Fix with base excision repair Double strand Break--> Fix with double-strand break repair (non-homologous end joining; homologous recombination)--> can be seen in Pancreas, Breast, Ovary tumors Adduct--> fix with nucleotide excision repair (can be seen in Xerodema pigmentosum Base insertion or deletion--> fix with mismatch repair (can be seen in colon and rectum tumors)

Postantibiotic effect

Some antibiotics show a persistent suppression of microbial growth after drug plasma levels have fallen below MIC --> Notable: aminoglycosides and fluoroquinolones Proposed mechanisms include: - persistence of the drug at the binding sites - need to synthesize new enzymes before growth can resume

MOA of Indirect Sympathomimetics (False NT's)

Some indirect acting sympathomimetics act as "false NT)- they displace NE from the storage vesicles When administered acutely (short-term) high concentrations NE travels to the synaptic cleft via NE transporter (NET) - NOTE: this is the reverse direction. NE in the synaptic cleft can activate adrenergic receptors When administered chronically (long-term): NE is replaced in the storage vesicles and the NE in the cytoplasm of the neuron is metabolized by monoamine oxidase (MAO). Subsequently when vesicle fusion and release is stimulated by an AP, there is reduced adrenoreceptor stimulation unless the "false NT" has direct adrenergic activity

Lead Poisoning

Sources: Environmental: - lead-containing house paints - flaking lead paint in older houses - pica (abnormal craving) for eating lead-based paint Occupational: - mining, foundries - pottery painting with lead-based paints - automobile industry: battery incineration Hobbies: - glazed pottery making, painting Lead poisoning in Children vs. Adults: Children: subclinical lead posioning with blood lead level <10microgram/dL - low intellectual capacity and behavioral problems Adults: mainly as an occupational hazard - Bone marrow, GI, and CNS involvement

Tobacco

Sources: - Cigarette smoking - Smokeless tobacco (snuff, chewing tobacco) - Passive tobacco inhlataion ("second-hang smoke") Toxic components: - ** Polycyclic hydrocarbons: benzopyrene and benzanthracene** - Nitrosamines - Arsenic - Nickel - Hydrogen cyanide - Carbone monoxide - Formaldehyde - Nicotine Major Adverse affects: - Cancers (lung and laryngeal most common): also have bladder, esophagus, kidney, oropharynx, and pancreas carcinoma - COPD: chronic bronchitis and emphysema - Atherosclerosis (activate endotheliuM) - Prematurity, premature rupture of membranes, and Sudden Infant Death Syndrome (SIDS) 2 Most common types of lung cancer: Small and Squamous Cell Lung Carcinoma

Arsenic Poisoning

Sources: - Naturally present in soils and water - Used in wood preserversm herbicides, and other agricultrual products - Released in environment from mines and smelting industries - Present in Chinese and Indian herbal medicine - Arsenic trioxide used in treatment of acut promyelocytic leukemia (APML) - Inorganic arsenic present in ground water used for drinking in Bangladesh, Chile, and China Acute Toxicity: Potentially fatal, if ingested in large quantities Natural manifestation: 1. Vomiting, abd pain, diarrhea - garlic odor of breath and stool 2. QT elongation, torsades de pointes, other arrhythmias, and shock 3. Acute resp failure and death MOA: trivalent arsenic replaces phosphate in adenosine triphsophate--> interference with mitochondrial oxidative phosphorylation Chronic Toxicity: Skin lesions: - Hyper- or hypopigmentation, hyperkeratosis, scaling, etc. - Nails: white transverse lines (Mees lines) - Skin tumors: basal and squamous cell carcinoma (multiple, on plams and soles - PNS: symmetrical sensorimotor polyneuropathies - Other than skin malignancies: liver hemangiosarcoma, and bladder and lung carcinoma

Describe intiation by Polycyclic Hydrocarbons (Indirect Initiators)

Sources: fossil fuel, tobacco smoking, and smoked meat and fish Mechanism: production of epoxides, which form covalent adducts with DNA Induced Cancer: - Lung, oral cavity, and laryngeal carcinoma - Bladder carcinoma - Esophageal carcinoma Ex: Benzopyrene (a hydrocarbon) DNA adduct and lung carcinoma

How do we decide on how clean something has to be? (i.e. Not sterilizing the otoscope but only changing the tip)

Spaulding scheme - Critical items breach barriers, enter sterile sites (sterilization required)- i.e. Scapal - Semi-critical items contact broken skin or mucous membranes: likelihood of contamination with resistant pathogens is also taken into account, sterilization or high-level disinfection - Non-critical items contact intact skin only (i.e. BP cuff)- mid or low level disinfection usually OK NOTE: this may turn into something that is "semi-critical"- ie someone with burns on chest when listening to their heart

MOA of Aminoglycosides (mechanism of the antibacterial effect)

Step one: Reach Cytoplasm Penetration through the cell envelope by: 1. Diffusion through the aqueous channels (porin proteins) of the outer bacterial membrane 2. Active transport across the inner membrane (energy-dependent transport)- this process is dependent on electron transport and req. oxygen and alkaline pH **** The penetration through the cell envelope can be significantly improved by cell-wall active drugs (SYNERGISM) Step two: Inhibition of Normal Ribosomal Protein synthesis Aminoglycosides bind IRREVERSIBLY to the 30S ribosomal subunit and alter protein synthesis through 1. Blockade of the initiation complex (the complex formed for initiation of transition. It consists of 30S subunit, mRNA, tRNA and 3 initiation factors). This blockade leads to an mRNA chain with only a single ribosome on it, the so called monosome 2. Misreading of mRNA template which leads to the production of aberrant proteins- these proteins may be inserted into cell membrane so altering permeability and further stimulating aminoglycoside transport (energy-dependent phase II transport) 3. Blockade of translocation Simpler terms: - block of initiation complex - miscoded peptide chain - block of translocation

Bacteria derived from most environments are NOT pure. So how do we get pure cultures in isolation for further study?

Streak plate method for purifying bacteria complex mixtures Individual colonies that originated from a single bacterial cell - All cells here are clonally related since they arose from a single cell - Single colonies are colony forming units (CFU) - CFU of bacteria per ml of culture provides a way to determine the total # of bacteria IN streak plate: swipe swab 3 times using a new swab each time making sue to cross the swab before ONLY once

After doing a gram stain, you find that the organism is a Gram-positive cocci that is catalase negative.. this signifies it is

Streptococci/Enterococci (Anaerobes) - these can either be alpha-hemolytic, beta-hemolytic, non-hemolytic (gamma) Alpha-hemolytic: Streptococcus pneumoniae - Aerotolerant - Optochin susceptible - Bile-solube - Diplococci - No lancefield antigen result - Can be part of normal pharyngeal flora Viridans Streptococci: - Some are aerotolerant - Optochin resistant - Bile resistant - Normal oral flora - S. mitis is an important example* - Various Lancefield groups Beta-hemolytic: Streptococcus pyogenes - aerotolerant - bacitracin susceptible - PYR (+) - Lancefield group A - Can be part of normal pharyngeal flora Streptococcus agalactiae - aerotolerant - bacitracin resistant - PYR (-) - Lancefield group b Non-hemolytic (gamma) Enterococcus: - some aerotolerant - lancefield group D - black colonies on bile-esculin agar - normal GI flora - PYR (+) Some Streptococcus: - Clear colonies or no growth on bile-esculin agar

SOAP note

Structure: S (Subjective): What the pt tells you - history of sxs (CC, HPI) - relevant PMH, FH, SH ROS ** Remember to ask OLD CARTS P: Onset, location, duration, character, alleviating factors, radiation, temporal patterns, sxs, prior episodes O (Objective): What you observe - PE (findings/signs) - Any available lab/xray results A (Assessment): What you think is going on - Problem list/differential diagnosis - If acute: differntial diagnosis with clinical reasoning possible causes - If chronic: current status of each problem including comments about potential complications related to that chronic problem, for ex, retinal disease or peripheral vascular disease in pt with hypertension P (Plan): What will you do - "Work-up" and/or management plan - If Acute: Diagnostic work-up and any other appropriate management - If Chronic: management is the main focus, but may include tests to screen for complications ** Important to document pt education and discussion here** EX of SOAP note: S: Has had only 2 headaches, both mild and without associated sxs. These are less troubling- cannot detect any precipitating factors O: No tenderness over the temporal muscles. No papilledema A: Headaches improved, now without migraine features P: Call if symptoms recur Purpose: - Standard format for organizing pt info - Used for "daily update" or progress note for a pt who has already had a complete H&P done - Focused on active problems in hospitalized pt - Documentation of an office visit for a specific set of problems - Focused history and PE (not a complete H&P): provides enough info for readers to understand the pt problem, generate an appropriate differential diagnosis - General format of a verbal report (specific structure varies from service to service, across subspecialties, and inpatient vs. outpatient)

Antibiotics that Inhibit Nucleic Acid Synthesis or Function

Sulfonamides: - Sulfamethoxizole Diaminopryimidines: - Trimethoprim ** these can be usually used with sulamethoxizole Fluoroquinolones: - Ciprofloxacin - Levoflaxacine - Moxifloxacin Nitromidazoles: - Metronidazole

Antibiotics that work in the cytoplasm (inhibitor of nucleic acid syn. or function)

Sulfonamides: - via inhibition of dihydropteroate synthetase Trimethoprim: - via inhibition of dihydrofolate reductase Quinolones: - via inhibition of topoisomerases

What are two-component regulators?

System that allows ecternal stimulus to be converted into a genetic response; two separate proteins: 1. Membrane sensor kinase: - plasma membrane protein, senses something in the periplasm/environment (ex. temp, host-derived signals), autophosphorylates, transfers phosphate to a response regulator 2. Response regulator: - soluble cytoplasmic protein, transcripitonal activator or repressor, modified by phosphorylation (post translational modification)- binds DNA and turns gene off/on Ex: Staphylococcus aureus - AIP signal binds to a plasma membrane protein with a histidin-kinase sensor with a phosphate--> acts on AgrA (response regulator) which then gets phosphorylated and turns the operon gene on ** control a whole set of genes with just one signal

Bias

Systemic errors in study resulting in an incorrect estimate of the association between exposures and outocmes. Can be introduced throughout the research process can be seen when: - planning a study - recruiting participants (selection biases) - collecting the data - interpreting the results Types of Bias: Selection: persons in study are UNrepresentative of the true population - Non-participation: ppl who agree to participate differ systemically from those who decline (i.e. income level) - Attrition (aka dropout): ppl who make it to the end of the study differ from those that drop out (*seen in cohort studies) - Inappropriate Sampling (Sampling Bias) - Berksons Bias: sample is only taken from a subpopulation (ex. case and controls selected from hospital/clinic population only obscures the results) Measurement: info is gathered in distorted manner - Ex: faulty equipment, flawed survey instruments - Address with appropriate control group/ placebo group; check instruments/methods Recall: awareness of disorders alters recall of subjects - Common in retrospective studies - Ex: in case-control study- "cases" currently have disease and can recall more details about past exposures than "control" who are disease-free Solutions: Triangulation (use multiple sources to confirm info- ie pas tmed records and family members) Hawthorne effect: mere presence of investigator changes behavior of particpants Experimenter expectancy: researchers beliefs or desires are conveyed to study subjects - Modifying participants behavior through subtle cues or diff in treatment- subjects are somehow made aware of how the reasercher wants them to behave (Pygmalion effect or Rosenthal Effect) thinl: self-fufilling prophecy - solution: double blinidng/placebo group Observer Bias: observors prior knowledge of subjects or treatment conditions biases observations - solution: double blinding/placebo group Lead-time: early detection of a disease is misinterprested as increased survival - Better screening and diagnosis make it seem like survival has increased, but diseases natural history is unchanged - Major source of bias with screening tests Solutions: - Measure "back-end" survival - Stratify survival rate accordingly by evaluating severity of disease at the time of diagnosis Confouding: an outside factor related to both the exposure and outcome confuses the effect - An appearnace of a "causal realtionship" may be "spurious" bc both the purported "cause" and "effect' (outcome) are related to another variable (the confounder) that actually explains the true causal relationship i.e. Super Bowl and Domestic Violence

How do neoplastic cells leave the cell cycle?

THEY DONT! Neoplastic cells do NOT leave the cell cycle and do NOT complete diffentiate - Nml tissues ~1% of cells are within cell cycle - Benign neoplasms ~1-10% in cell cycle - Malignant neoplasma ~20-80% in cell cycle Indicator of proliferation: mitotic activity= number of mitotic figures - # of meta- and anaphases seen in 10 high-power fields (HPF) Ex: Mitoses in Sarcoma NOTE: Neoplasms (even malignant) differ in growth rate Cells, which are WITHIN the cell cycle, are susceptible for chemo- and radiotherapy** - Cancers with RAPID growth: high proliferative activity and high susceptibility to therapy - Cancers with SLOW growth: inhibited apoptosis, low proliferative activity, and resistance to therapy

T or F: Standard/Universal precautions are to be used ALL the time for infection control?

TRUE! These include: - Consider everyone/thing a potential source of infection - Handwashing/ sanitizing (before entry, before/after pt contact, before gloving, after degloving, after touching fluids or contaminated items, before exit) - Personal protective devices when contact with body fluids is anticipated and for certain procedures (ex. aerosol-generating)- gloves, masks, googles, face masks, gowns, resuscitation equipment - Cough etiquette - Sharps, injections, linens- safety precautions - Limit surfaces touched (so you know what to clean) - These are used ALL OF THE TIME!

T or F: There is NO parasympathetic activation of blood vessels

TRUE! there is only sympathetic activation of blood vessels Alpha1, alpha 2 do: - constriction of coronary arteries and arterioles - constriction of skin mucosa - constriction of veins Alpha1 does: - constriction of arteries and arterioles in skeletal muscle Beta2 does: - Dilation of coronary arteries and arterioles - Dilation of arteries and arterioles in skeletal muscle - Dilation of veins ** There is NO parasympathetic innervation- vasodilation does NOT occur when the parasymp NS is discharged- however drugs that directly activate M3 receptors will cause vasodilation M3- acting on vascular endothelium--> Vasodilation: redults from endothelium derived growth factor and nitric oxide (NO)

40y/o woman started taking naproxen to relieve pain and inflammation associated with a swollen limb. She explains that she started to experience gastric upset after taking the mediaction. What advice would you provide to the woman to reduce the ocurrence of this side effect?

The following options are possible: - Woman should be advised to take naproxen with food as this would decrease the GI irritation - As an alternative (if this does not work), the woman could also consider taking a COX-2 selective NSAID ex. celecoxib (ensure that she has no cardiovascular conditions or is at risk of developing such) - The co-administration of a drug such as a proton pump inhibitor (ex. omeprazole) or H2-antagonist (famotidine) to decrease the production of gastric acid

Resistance to Fluoroquinolones (Ciprofloxacin, Levofloxacin, Moxifloxacin)

The widespread use of fluoroquinolones has contributed to the rapid emergnece of resistance worldwide. It is plasmid mediated Resistance develops mainly among S. aureus, P. Aeruginosa and Serratia marcescens Resistance is generally crossed among fluoroquinolones Mechanisms: 1. Change in the target enzyme DNA gyrase 2. Decreased permeability of the bacterium to the drug 3. Increased activity of the multidrug efflux pump

Describe the replication of Double-stranded DNA viruses

These viruses may use the host cell machinery to replicate their DNA or not - Those that require hosts DNA polymerase need to infect cells that divide rapidly in order to gein access to the hosts ensyme (if they infect rapidly dividing cells, this is easily done) - Viruses that do not infect rapidly dividing cells solve the problem of DNA polymerase accessibility by inducing the cell cycle - Other viruses encode their own DNA pol thereby freeing them from having to replicate their DNA during S phase Viral dsDNA is transported to the nucleus where it can either be 1. amplified by cellular DNA-dependent DNA polymerase (req. dividing cells) or 2. transcribed into mRNA by cellular DNA-dependent RNA pol (RNA pol II) to synthesize viral DNA-dep DNA pol then used to amplify viral dsDNA - there is dsDNA and mRNA synthesis - Some of dsDNA will be packaged into newly formed capsid, but some will serve as template for mRNA transcription - mRNA is then transported to ER where it will serve as template for mRNA transcription - that mRNA will be transported to the ER where it will in turn serve as template for protein synthesis (proteins will be involved in gene regulation, virulence, and actual assembly of viral particles) - Glycoproteins destined to be embedded into viral envelopes go through golgi apparatus NOTE: - dsDNA viruses that replicate in cytoplasm, as opposed to nucleus must encode their own DNA-dependent DNA polymerase and DNA-dependent RNA polymerase (ex. Poxviruses) - Most dsDNA viruses that replicate in the nucleus, encode their own DNA-dependent DNA polymerase anyway (ex. herpesviruses)

Thioglycollate

Thioglycollate removes oxygen - A tube of semi-solid medium containing thioglycolate is inoculate with the test organism and incubated under normal conditions, allowing oxygen to diffuse into the medium from the top - This produces an oxygen gradient in the tube - Obligate aerobes will grow only at the top - Facultative anaerobes will grow throughout but usually better at the top - Aerotolerant anaerobes will be able to grow throughout most of the tube - Strict anaerobes will grow near the bottom of the tube - Where ould a microaerophile grow? somewhere in middle?

What is the difference between thromboxane A2 and PGI2 (prostacyclin)?

Thromboxane A2 causes platelet aggregation whereas PGI2 (prostacyclin) inhibits platelet aggregation

Antimicrobial action can be time dependent or concentration dependent- differentiate between the two

Time dependent killing: Some bactericidal antibiotics do NOT significantly increase the rate of killing as the concentration increases --> Notable: penicillins, cephalosporins, and vancomycin ** Rate of killing is proportional to the time that the blood conc. remains above the MIC Concentration dependent killing Some bactericidal antibiotics show a significant increase of bacterial killing as the blood concentration increases ---> Notable: aminoglycosides and fluoroquinolones ***Giving high doses of these once a day can achieve high PEAK levels, favoring rapid killing

What type of vaccine is polio, Salk- inactivated

Tivalent (IPV, Salk vaccine), adjuv. - Should be given to children

Intravenous (IV)

To achieve systemic effects- drugs injected directly into the general circulation Absorption: - immediately available in systemic circulation Advantages: - can have immediate effects - ideal if dosed in large volumes - suitable for irritating substances (to GI) - valuable in emergency situations - dosage titrations permissible - ideal for high molecular weigh proteins and peptide drugs Disadvantages: - unsuitable for oily substances - bolus injection may result in adverse effects - most substances must be slowly injected - strict aseptic techniques needed

Environmental factors that influence cancer

Tobacco smoking: - carcinoma of the lung, oral cavity, larynx, esophagus, pancrease, and bladder Alcohol abuse: - hepatocellular, oropharyngeal, laryngeal, esophageal carcinoma Physical factors: - ionizing radiation: leukemia, thyroid and bone cancer - UVL: skin cancer (carcinoma and melanoma) Lifelong exposure to estrogens (especially, if not opposed by progesterone): breast and uterine carcinoma Occupational hazards

Antibiotics

Today the term antibiotic has become synonymous with antibacterial drug Classification: - class and spectrum of microorganisms it kills - biochemical pathway it interferes with - chemical structure **Ideally antibiotics block the vital functions of microbes without affecting those of the host cells ---> SELECTIVE TOXICITY (that is they have the ability to injure or kill microbes while having minimal effects on the host cells)

What vaccine should you use for Carynebacterium diphtheriae (diphheria) (TDaP)

Toxoid Vaccine Type - should be received by: children, adolescents, and adults and pregnant women

Differentiate translational control in prokaryotes vs. eukaryotes

Translation= RNA--> Protein Prokaryotes: - transcripition and translation are tightly coupled - pirmary transcript serves as mRNA - mRNA may be polycistronic Eukaryotes: - transcription and translation are spatially separated - primary transcript is processed (RNA splicing and 3' end modification) and exported to the cytoplasm - mRNA is monocistronic Regulation of translation: - less efficient (mRNA made but not used) - faster response (mRNA already there) - aka post-transcripitonal regulation Several mechanisms: - mRNA stability (must anchor proteins to it to keep it around, other wise it will just leave) - ribosome binding site efficiency (sequence, spacing) - antisense RNAs: small RNA oligonucleotide that is complementary (antisense) to a mRNA sequence: blocks translation - can covalently bind to mRNA- if present ribosome CANT bind

Adverse Effects of Antimuscarinic Drugs

Treatment with antimuscarinic drugs is usually directed at one organ system. However treatment will have effects on multiple organ systems. The unwanted/unintended effects are adverse effects. Most of the adverse effects are predictable; opposite of the effects cause by muscarinic agonists Anticholinergic drugs that distribute to the CNS are identified by the Beers Criteria as potentially inappropriate medication that should be avoided in pts 65 yrs and older Beers Criters: a list of medications considered potentially inappropriate for use in older pts due to high risk of adverse events **There are many drugs with anticholinergic effects that are not specifically targeted to cholinergic receptors. Ex: first generation antihistamine diphenhydramine

Bacteria exhibit specificity (aka _______) during attachment

Tropism: where an organism wants to go (ex. Gram negative bacteria work in the GI, so if you breathe it in it will not get you sick because it will not know what to do in that location) Bacteria and the tissue they colonize in: - Corynebacterium diphtheriae (pharynx) - Neisseria Gonorrhoeae (Urogenital epithelium) - Streptococcus mutans (tooth surfaces) - Streptococcus salivarius (tongue surfaces) - Vibrio cholerae and Escherichia coli (small intestine epithelium) - Staphylococcus aureus (nasal membranes) - Staphylococcus epidermidis (skin)

In the case of a pt with possibly MI damage involving the left lateral ventricular wall- which lab test may be useful in this situation

Troponin levels

T or F: Bacterial Normal Flora can provide protection against, or be a source of infection

True

T or F: You cannot refuse to transfer records requested by the pt (or authorized representative) for ANY reason!

True! State laws govern how long medical records need to be kept - by law, most providers keep records for no less than 10 yrs after a pts last visit - HIPAA privacy rule does not determine how long records are kept but does require that all safety guidelines necessary to protect privary are in place as long as that info is stored

Gram stain would not be very useful in identifying a causative agent in stool- T or F?

True! Stool is made of lots of normal microbiota so staining would not be very useful

T or F: Acetaminophen is NOT considered an NSAID

True! it is used to relieve pain and fever - It is the analgesic/antipyretic of choice for children due to the risk of Reye Syndrome with aspirin Acetaminophen is a weak COX-1 and COX-2 inhibitor in peripheral tissues and possesses no significant anti-inflammatory reffects - it inhibits prostaglanding synthesis in the CNS, leading to antipyretic and analgesic effects (less effect on cyclooxygenase in peripheral tissues due to peripheral inactivation) NO affect on platelet function, gastric mucosa, kidney perfusion, asthmatics

Characteristic Features of Neoplasia

Uncontrolled growth - Growth of nml tissue is always controlled- cell proliferation increases only as a reparative process for replacement of dead or dying cells - Uncontrolled neoplastic growth, aka evasion of host control over the cell/tissue growth via: activation of growth promoting factors, inhibition of growth-suppressing factors, evasion of apoptosis, limitless replicative potential (immortalization), and loss of contact inhibition Increased growth rate - Growth rate reflects a balance between cell production and cells lost - Increased growth rate--> an increase in number of neoplastic cells - A neoplasm grows (i.e. accumulates cells) faster than normal tissues bc of 2 factors: 1. Retention of cells in the cell cycle (duration of cell cycle is not affected (~24hr) 2. Inhibition of apoptosis Lack of differentiation - Neoplastic cells, which are within the cell cycle, CANNOT differentiate - Malignant tumors: many cells are within the cell cycle, therefore, the cells (and tissues, which they form) do NOT resemble to the cells/tissues of origin of neoplastic growth - Benign tumors: proliferating activity is low, therefore their cells (and tissues) are always differentiated Tissue and cellular atypia - Abnormal tissue architecture Monoclonality - all tumor cells originate from a single precursor cell Progression - many tumors get more aggressive

The human body is teaming with microbes. The vast majority do NOT cause disease. It is therefore important to distinguish normal flora from pathogens.. How is this done?

Unique aspects of bacterial growth can be used to differentiate and identiy bacterial pathogens in complex mixtures Use: Selective media: One which has a component added to it which will inhibit or prevent the growth of certain types or species of bacteria and/or promote the growth of desired species **Usually agar media - add component that inhibits growth of while aiding growth of other Differential media: One which allows the investigator to distinguish between different types of bacteria based on some observable trait in their pattern of growth in the medium ** relies on observable trait MacConkey is a differential AND selective media: Selective: Bile salts and crystal violet that inhibit the growth of most gram postiive bacteria Differential: - Lactose, peptides, and neutral red (pH indicator) - Lactose fermentation- acid (red if able to ferment lactose) - if organ is able to ferment lactose it will produce acid and the plate will be red - Non lactose fermentation- use peptides- colorless (bc no acid is produced) ** MacConkey is for gram negative organisms bc bile salts prevent the growth of gram positive Lactose positive enterics: - Klebsiella - Enterobacter (more pinkish than salmonella) - Escherichia coli Lactose negatives: (does NOT form lactose) - Salmonella

"Side effect" and "adverse effect" of a drug

Unwanted drug effects are usually classified according to diff criteria: either the freq of their appearacnce (freq or rare effects), seriousness (light or serious effects), or their underlying mechanisms Side effects: are undesirable, NON-DELETERIOUS drug effects occurring after administration of standard therapeutic doses and are related to the pharmacological properties of the drug ** Most often pt is advised to continuing taking the drug and side effects will subside Adverse effects: are undesirable, DELETERIOUS drug effects occurring after administration of standard therapeutic doses- some adverse effects are predicatble and dose-dependent, and may be mild, moderate or severe- some adverse effects are unpredictable

How are specimens processed?

Urine, sputum, stool, etc. : Microscopy: - gram stain for most - specific techniques ex. ova and parasite (O+P) trichome stain for stool, acid-fast stain if AFB suspected (sputum, CSF) - rapid antigen tests - directly cultures onto media Blood: - inoculated into bottled for enrichment - growth monitored - then stained, cultured

Immunoflourescence

Use of antibody tagged fluorescent compounds Direct test: - labeled antibody is allowed to bind to antigen that is fixed on a slide - specific labeled antibody is applied Indirect test: - antibody is allowed to bind to antigen and the antibody is detected by binding with tagged anti-antibody Ex of DIRECT (in which fluorescein-tagged antibody (primary antibody) may be used to detect an antigen: Ex: Confirmatory test for syphilis - absorbed srum is reacted with Treponema pallidum antigen on a slide - any antibody bound to the antigen is then detected with fluorescein labeled anti-humen IgG - this is a FTA-ABS test *** Any material may be detected by immunofluorescence if tagged antibody is available - Ex: flourescein-labelled antibody to Neisseria gonorrhoeae may be used to demonstrate the presence of the organism

Detection of a specific microbial antigen

Use when speed is crucial to prognosis - ex: antigen detection assays on CSF specimens for causes of meningiitis Use antibodies to detect antigen - agglutination, immunoassay, immunofluorescence - NOT detecting patients immune response - confirmatory assays are usually necessary (usually cant be both fast and good)

Defenses of the Highly Educated

Using the minds higher functions to ward off distress: Intellectulization: - I.e. Dr. smith broke bad news about brain tumor by launching a detailed lecture on neurological underpinnings of stage 4 glioblastoma (easier than talking to pt about brain tumor) Rationalization - i.e. After being angrily confronted by pt for giggling during sensitive medical history, doc replies " i was simply attempting to make you comfortabtle" - hes trying to think of a rational reason why he would be have the way he did Isolation of affect - I.e. Dr. wilson discussed golf game with colleague as he sawed away at the ribs of his pt whom he was perfoming open heart surgery

What are the features of the antibacterial effect of beta-lactam antibiotics?

Usually both mechanisms are operative and the ultimate effect is BACTERICIDAL- when only the 1st mechanism is operative the ultimate effect is BACTERIOSTATIC (in this latter case the microorganism is said to be tolerant to the anitbiotic) Bactericidal effect is time-dependent (killing doe NOT increase with increasing concentrations above the MBC, but continues as long as serum concentrations are greater than MBC) Susceptibility of bacteria to beta-lactam antibiotics depends on: - the constitution of the outer layers of the cell envelope that the antibiotic must cross - the thickness of the peptidoglycan layer (thickness is much higher in gram-positive bacteria than in gram-negative bacteria)

What are viruses?

Virsues contain EITHER DNA OR RNA, and are incapable of propagation outside a living cell - Obligate intracellular parasites Virion: complete virus particle Phage: virus that infects bacteria (antibiotic resistance) Capsid: outer protein coat that protects the viral nucleic acid - Single-stranded or double-stranded DNA or RNA in capsid (may take a variety of forms (ex. circular, linear) - Size from 20-300nm (very small!)

Role of Antibodies in adaptive immunity

Virus neutralization - VAP blockage - MAC activation - Uncoating inhibition Antibodies produced by this response will be distributed systemically (blood) or locally (mucosa-associated lymphoid tissues or MALTs) and will serve to neutralize viruses (by binding to viral surface proteins & glycoproteins thereby interfering with viral adhesion, entry, & uncoating processes), creat immune complexes (by clumping viral particles together or with erythrocytes so that they can taken up and destroyed by macrophages), as well as opsonize them for complement activation (classical activation of complement of enveloped virus) ** Immune complexes - CR1-mediated Small antigen:antibody complexes form in the circulation--> Activation of complement leads to the deposition of many molecules of C3b on the immune complex --> complement receptor CR1 on erythrocytes binds the immune complexes via bound C3b --> In the spleen and liver, phagocytic cells remove the immune complexes from the erythrocyte surface ADCC Antibody binds antigens on the surface of target cells--> Fc receptors on NK cells recognize bound antibody--> Cross-linking of Fc receptors signals of the NK cell to kill the target cell--> Target cell dies by apoptosis

When should Contact precautions be used?

When efficient transmission by direct or indirect contact with the pt or environment - Clostridium difficile and other enteric infections - Some pyogenic infections - Cutaneous anthrax - Antibiotic-resistant organisms - Avian influenze - RSV, HSV, enterovirus, parainfluenza - chickenpox (VZV) - smallpox - SARS - lice - scabies - Ebola USE standard precautions + - Private room (may cohort same pathogen) - Gloves, gowns upon entry and during pt transport - Clean hands between tasks - Dedicated equipment ** NOTE: several of these require droplet or airborne precaustions as well

When should Airborne/Aerosol Precautions be used?

When there is efficient transmission by aerosols (droplet nuclei, <5 micrometers) - Avian influenze - Pulmonary tuberculosis - Measles - Chickenpox (VZV) - Smallpox - SARS - monkeypox Use Standard precautions + - Negative-pressure private closed room with air exhausted through HEPA filter or outdoors -- AIIR-'airborne infection isolation room' - Closed door - Respirator mask (N-95) required to enter (also for aerosol-generating procedures with potential pulmonary pathogens ex. bronchoscopy) - Mask pt out of room - Controlled entry to visitors/personnel - Notification

Live vaccines (another active immunization)

When vaccine contains live organism it is either avirulent or attenuated - Attnuated by growth at non-physiologic temp (23-34*C) in embryonated eggs, on non-natural hosts, or in tissue or cell culture, leadings to selection of mutants that are less virulent - Reduced virulence can be achieved by: poor growth at 37*C, inability to grow well in human cells, or inability to escape immune control - Loss of ability to infect target tissue typically affected by disease can be form of attenuation i.e. Polio vaccine ( a neurotropic virus) contains attneuated virus that replicates in GI tract, but cant reach or replicate in the brain - Also possible to vaccinate with an organism that provides cross-protection such as smallpox vaccine that consists of live vaccinia virus- vaccina is diff species than smallpox- but it shares antigenic determinats such that immunity from vaccinia (cowpox) protects from smallpox In other live vaccines, the virus has been genetically engineered to lack virulence- HYBRID virus vaccines are a form of genetically engineered vaccine in which genes from infectious agents that cannot be attenuated are inserted into viruses of low virulence These mimic natural infection with organism, so the immune resp generated progesses through both Th and Tfh immune responses, with development of cellular, humoral, and mamory immune responses; these vaccines also tend to stimulate effective innate responses - As result of limited replication of the immunizing organism, persistence of antigenic determinatnts allows development of a full immune response- responses are therefore more robut and longer-lived than those generated using killed organisms or subunits *** Main objective of this type of immunization is to promote protective immune resp, while limiting disease

Intimate Partner Violence (IPV)/ Domestic Violence (DV)

Willful intimidation, physical assault, battery, sexual assault, and/pr other abusive behavior as part of systemic pattern of power and control perpetrated by one intimate partner against another (phys, sexual, psych, emotional) Stats: - 1 in 3 women and 1 in every 4 men have been victims of some form of phys violence, sexual violence or stalking by an intimate partner in their lifetime - Domestic vicitmization is correlated with higher rate of depression and suicidal behavior - only 34% ppl who are injured by IPV receive medical care IPV/DV is NOT mandatory reportable offense in most states Reporting IS required when: - injuries are due to use of guns, knives, or other deadly weapons - injuries caused in violation of criminal law - death or imminent threat to life involved ***Criminal intervention is NOT always the best/safest response for victims- fear of reporting and law enforcement may make them feel they have no choice but to withhold info from health care providers or avoid med attention entirely BARRIERS to leaving IPV - mix of good times - abusers action may become more violent/lethal if attempt to leave - unsupportive fam and friends - lack of support/finanncial means - lack of knowledge to safety and support - lack of having somwhere else to go - religious or cultural beliefs - belief that 2 parents household are better for children, despite abuse

Insufficiency in Nucleotide Excision Repair can lead to

Xeroderma Pigmentosum Inherited defect in nucleotide excision repair--> inability to repair pyrimidine cross-links induced by UVL--> Skin cancer (Squamous cell carcinoma, Basal cell carcinoma, and Melanoma)

Are spontaneoud mutations rare in bacteria?

YES! - One gene= ~10^3 bp - Chromosome= ~5 x 10^6 bp 10^3bp/5x10^6 bp or 1/5000bp (if there is an equal, randomw chance of a mutation in any base on the chromosome, and there is an average of one mutation per cell, then this is the probability that a mutation will ocur in any particular gene) However, many mutations result in silnt mutations. It is estimated that ~90% of all singl base substitutions are silent. Thus, the probability that a phenotypically detectable mutation will occur in any particular gene is: 1/5x10^4bp Using a simple screen with ~200 colonies/plate you would need 250 plates to find a single mutant

Can an antibiotic be bactericidal for one organism but bacteriostatic for another?

YES! These are relative terms - It is possible for antibiots to be bacteriostatic for one organism and bactericidal for another - Also high concentration of some bacteriostatic agents are also bactericidal, wheresas low concentrations of some bactericidal agents are bacteriostatic

Differentiate between zero and first order

Zero order: rate of drug metabolism is NOT proportional to drug concentration- it is CONSTANT - an increase in plasma drug concentration does NOT increase the rate of drug meatbolism - occurs only with a few drugs: ethanol, phenytoin, salicyclic acid, theophyllin, warfarin, heparin and some barbiturates - Ethanol is best ex.- NO MATTER the quantity of the drug in the body, ethanol is matbolized by the liver at the rate of ~10g/hr First order: rate of drug metabolism IS proportional to drug concentration - an increase in plasma drug concentration increases the rate of metabolism - occurs with MOST drugs Rate of metabolism vs. Drug concentration plot: - zero order reactions: rate of metabolism is CONSTANT - first order reactions: rate is proportional to the drug concentration Plasma drug concentraion vs. Time plot: - zero order: LINEAR decline of the concentration with time - first order: exponential decline of the concentration NOTE: If a plot of log concentration is done vs. time for drugs which follow first order kinetics- a straight line is obtained - First order elimination: a constant fraction of drug is eliminated whereas with zero order elimination a constant amount of drug is eliminated **Be able to differentiate the graphs of first order vs. zero order kinetics

Microorganisms can acquire antibiotic resistance by temporary or permanent alteration of microbial genetic information- resistance is due to the following changes of microbial DNA

a) Spontaneous mutations of DNA - Chromosomal mutations can produce antibiotic resistant strains which can proliferate under antibiotic selection that dstroy non-resistant strains b) DNA transfer of drug resistance - Resistance propertied can be encoded in extrachromosomal R factors (resistance plasmids) which can enter other microbial cells, thus transferring resistance

Transcripiton of bacteria may be controlled by

activation and repression - No activator present --> No transcription occurs - Activator present --> transcription occurs - No represser present--> transcription occurs - Repressor pressent--> No transcription occurs Ex: Lac operon - 3 genes clustered on chromosome to use lactose (lac Z codes for beta-galactosidase, lacY codes for lactose permease, and lacA which codes for galactoside transacetylase) on escheria coli - LacP= promoter to transcribe these 3 genes as single polycistronic mRNA - lacO operater thats involved in transcriptional reg of lac operon Lac operon= region with lacP, lacO, lacZ, lacY, lacA lacI= regulatory gene makes lacrepressor protein (when active it binds to lac operator site--> RNA polymerase cant recog promoter and genes are not transcribed) Lactose--> allolactose via beta galactosidase binds to lactose repressore causing conformation change that does not allow it to bind to the lacoperator (without active lac repressor to operator - RNA poly binds promoter and transcribes 3 genes and then this polycistronic mRNA makes their 3 proteins

List the sympathetic effects and the sympathetic receptors on blood vessels

alpha1, alpha2: - constriction of coronary arteries and arterioles - constriction of arteries and arterioles in skin & mucosa - constriction of veins beta2: - dilation of coronary arteries and arterioles - dilation of arteries and arterioles in skeletal muscle - dilation of veins alpha1: - constriction of arteries and arterioles in skeletal muscle NOTE: there is NO parasympathetic innervation: vasodilation does NOT occur when the parasympathetic nervous system is discharged- However drugs that directly activate M3 receptors will cause vasodilation - M3 causes vasodilation (results from endothelium derived growth factor and nitric oxide (NO) in vascular endothelium

Aqueous diffusion of drugs across cell membranes occurs through

aquaporin protein channels of cell membranes that cross the lipid bilayer - this is a passive and non-selective process Dependent on: - number of protein channels - concentration gradient - water solubility - molecular size of the drug (the passage of large molecules is restricted) --- passage of molecules >100D is restricted NOTE: - Passive diffusion of water-soluble drugs req a aqueous channel or pore, whereas passive diffusion of llipid-soluble drug is dissolved in a membrane

Pharmalogical effects of epinephrine on blood pressure

are DOSE DEPENDENT! Low dose (beta2>alpha) - decrease in BP (vasodilation due to beta2 activation) Medium dose (beta2~alpha) - systolic BP increases (due to increase in CO) - diastolic BP decreases (vasodilation due to beta2 activation) - increase in systolic pressure is greater than decrease in diastolic pressure so the pulse pressure increases - mean BP is not greatly elevated, therefore compensatory baroreceptor reflexes do not usually antagonize direct cardiac actions High dose (alpha>beta2) - Both systolic and diastolic pressure increase (alpha receptors are present on all vasculature including muscle vasculature. At high concentration of epinephrine the effect of the alpha receptors overcomes the effect of the beta2 receptors bc alpha receptors are greater in number

Autonomic physiology is key to understanding

autonomic pharmacology Peripheral NS consists of ANS and SomaticNS ANS has 2 anatomical divisions: SNS and PSNS - both the parasympathetic and sympathetic divisions of the ANS consist of two neurons- preganglionic neurons have cell bodies that are located in the CNS - ALL preganglionic neurons are cholinergic (use acetylcholine) - Postganglionic parasympathetic neurons are cholinergic - Postganglionic sympathetic neurons are noradrenergic, commonly called adrenergic (use norepinephrine), except for the sweat glands that use acetylcholine - Sympathetic nerves to the renal vaculature and kidney may release dopame in times of stress - The adrenal medulla is a modified sympathetic ganglion that receives sympathetic preganglionis fibers and releases epinephrine and norepinephrine

Varicella-Zoster Virus (VZV)

causes chickenpox (varicella) - upone recurrence causes herpes zoster, or shingles It is a alphaherpes virus- so shares many characteristics with HSV such as: 1. ability to establish latent infection of neurons and recurrent disease 2. important of cell-mediated immunity in controlling and preventing serious disease 3. characteristic blister-like lesions - Like HSV, VZV encodes a thymidine kinase and is susceptible to same anitviral drugs - UNLIKE HSV, VZV spreads predominantly by resp. route and after local replication of virus in resp tract, by viremia to form skin lesions over the entire body ** Like HSV, VZV establishes a latent infection of neurons, unlike HSV several viral RNAs and specific viral proetins can be detected in the latently infected cells

Somatization

converting feelings into physical sxs and focusing ones attention on somatic (rahter than intrapsychic) concerns Ex: A woman says she is not sad about her divorce, but complains of headaches and GI upset

In the absence of T cells (ex. in tissue culture), EBV can

immortalize B cells and promote development of B-lymphoblastoid cell lines - B-cell activation and prolifection in vivo occurs and is indicated by the spurious prodcution of an IgM antibody to the Paul-Bunell antigen (heterophile antibody) Outgrowth of the B cell is controlled by nml T cell response to B cell prolif. and to the EBV antigenic peptides B cells are excellent antigen-presenting cells and present EBV antigens on both MHC I and MHC II molecules - the activated T cells appear as atypical lymphocytes (also called Downy cells) --> they increase in number in the peripheral blood during the second week of infection, accounting for 10-80% of the total white blood cell count at this time (hence the "mononucleosis") ** Atypical T-cell (DOwny cell) is a characteristic of infectious mononucleosis NOTE: classic lymphocytosis, swelling of lymphoid organs, and malaise associated with infectious mono result mainly from the activation and proliferation of T cells - Sore trhoguh due to response to EBV infected epithelium and B cells in tonsils and throts During productive infection, antibody first developed against components of the virion, VCA, and MA, and later against EA **T cells are essential for limiting the proliferation of EBV-infected B cells and controlling the disease EBV counteracts some of the protective action of TH1 CD4 T-cell responses during productive infection by producing an IL-10 analog (BCRF-1) that inhibits the prote ctive TH1 CD4 T cell repsonse and also stimulates B-cell growth ""kissing disease"" ** there are no modes of control

Type I interferons (IFN-alpha and IFN-beta) are important as

initial means of viral infection containment - when infected cell recog. dsRNA, it response by expressing a set of many IFN-inducible genesincluding the genes that encode for IFNalpha/beta and their receptor (IFNAR) - leads to an increase in conc. of type I IFNs in vicinity of infected cell----> with concomitant up-regulation of INFAR receptors on the surface of the infected cell itself and its neighbours -- positive feedback loop creates an antiviral state centerd on the infect cells Cell surface exp. of class I MHC is decreased, whereas Fas is up-regulated, in an attempt to increase the likelihood of a cell to be recognized and killed by NK cells during the initial phase of the immune response, whereas others will lead the cell on one of numerous paths of self-destruction (apoptosis, autophagy,etc) Major paths that lead to IFN-alpha/beta-mediated apoptosis are the PKR (protein kinase R or eukaryotic translation initiation factor 2-alpha kinase 2) and 2'-5'-oligo(A)synthetase /RNase L pathways Upon type I IFN stimulation, the cellular concen. of inactive PKR increases - dsRNA then complexes with 2 PKR molecules with auto-transphophorylate one another Activated PKR then phosphorylates the alpha subunit of translation intiation factor eIF2 which then irreversibily binds the guanine nucleotide exchange factor eIF2B and hinders GTP recycling from GDP, thus bringing protein synthesis to a halt Absense of protein syn--> apoptosis Similarly- IFNalpha/beta stimulation increases the cellular concentration of inactive 2'- 5' oligo (A) synthetase and RNase L - binding of dsRNA to 2'-5'oligo (A) synthetase activated 2'-5' olgio (A) synthetase which yields 2'-5' adenylic acid from ATP which in turn activates RNase L - Cellular RNA is therefore degraded and protein synthesis is once more brough to a complete stop - In absence of protein syn--> apoptosis Other intrinsic cellular defenses include nuclear domain 10-associated proteins (such as PML, Sp100 & Daxx), often referred to as nuclear domain 10 bodies (ND 10 bodies), which act as DNA transcription inhibitors that hinder DNA virus replication, as well as RNA silenxing which can act on both DNA and RNA viruses

Shock

is the failure of adequate perfusion and oxygenation to the body - State of shock is usually suspected at SBP<90mmHg- clinical assessment and laboratory evaluation is needed for confirmation and identification of shock Types of Shock: Distributive: - Anaphylatic: seen in pts with severe allergies to foodborne allergens, drugs and inset bites. Histamine mediated - Septic: caused by systemic inflammation and persistent hypotension due to the interaction between microbes and the innate and adaptive immune system- *Most common type of shock in ICU patients - Neurogenic: seen in traumatic brain and spinal cord injuries - Endocrone: seen in pts with mineralcorticoid deficiency Cardiogenic: critical end organ hypoperfusion due to reduced cardiac output- the most common cause of cardiogenic shock is myocardial infarction (MI) Hypovolemic: seen in any situation where the circulating blood volume is decreased- most common manifestation is blood loss from GI bleeding or traumatic blood loss- May also be caused by vomiting, diarrhea or dehydration. Usually resolved with fluids and/or blood transfusion Obstructive: seen where there is a blockage to cardiac output and can occur due to an acute increase in pulmonary vascular resistance (PVR) or from mechanical obstruction of the heart. Pulmonary embolus and severe pulmonary hypotension are the most common causes of increased PVVR- The most common causes of mechanical obstruction are cardiac tamponage and tension pneumothorax ** this kind of shock is usually resolved with surgical intervention such as pericardiocentesis or thoracostomy

Bactericidal drug

kills sensitive organisms at serum levels achievable in the pt, so that the number of viable organisms falls rapidly after exposure to the drug * these produce more rapid clinical improvement and are less likely to elicit microbial resistance --> bc of their more aggressive action bactericidal drugs are FIRST LINE agents in seriously ill or immunocompromised pts*** Main bacteridical drugs include: - Beta-lactams, Vancomycin, Fosfomycin (all cell wall syn. inhibitors) - Aminoglycosides - Fluoroquinolones - Sulfonamide-Trimethoprim (comb.) - Quinupristin-Dalfopristin (comb.) - Isoniazid - Rifampin - Pyrazinamide

Facilitated diffusion is mediated by a

protein carrier - Does NOT require energy bc drug moves along a concentration gradient (high conc. --> low conc.) - It is carrier mediated so it is saturable and structurally selective for the drug and shows competitions for drugs of similar structure

Volume of distribution (Vd)

the fluid volume that is required to contain the entire drug in the body at the same concentration measured in the plasma Vd= Dose of drug/ Drug concentration Ex: If pt received 7mg of drug X and the blood sample has a concentration of 1mg/L. It would mean that Vd is 7L Vd= 7/1= 7L * Vd is independent of the dose of drug (therefore it is constant) If is drug is given IV, the bioavailability (F) is 1. However, if the drug is given by any other route, the F must be considered such that: Vd= (Dose of the drug x F)/ (Drug concentration (Cpo)) Cpo is the plasma concentraion at zero time or the initial plasma cocentration Ex: 1000mg of a drug is given IV and the resultant concentration is 0.01mg/ml. What is the volume of distribution of this drug? - If the drug is given IV, the F is 1. Therefore the Vd= (1000mg x 1)/ (0.01mg/ml)= 100,000 ml (or 100L) ** You can also use this formula to determine suitable dose to administer. Ex; if you know Vd and desired plasma conc, you can use the formula to calculate a suitable dose for a pt (dont forget to take bioavailability into consideration)

Bacterial replication occurs using the

theta model - Initiated at a single origin of replication - Proceeds bidirectionally "Bidirectional DNA replication" Genetic info in bacterial cell in ds covalently clsoed circle of DNA - rep begins are ORI - originn replicates and DNA rep proceeds in 2 directions - the two original strands, serve as templates for syn of new strands --> semiconservative replication

Strongyloides stercoralis

threadworm (common name) Complex life cycle: many larvae produced especially in immunocompromised persons, leading to very high parasite load - auto-reinfection infective larvae penetrate skin (GROUND ITCH) Adults in the intestine - larvae in the stool

EBV is a member of the subfamily gammaherpesvirinae, with a very limited host range and

tissue tropism (defined by the limited cellular expression of its receptor) **Primary receptor for EBV= receptor for C3d component of the complement system (aka CR2 or CD21) - it is expressed on B cells of humans and New world mokeys and on some epithelial cells of the oropharynx and nasopharynx- EBV also binds to MHCII 3 potential outcomes of EBV infection include: 1. Can replicate in B cells or epithelial cells permissive for EBV replication and produce virus 2. Can cause latent infection of memory B cells in the presence of competent T cells 2. Can stimulate and immortalize B cells

Goal of vaccination

to promote the development of immunity - Vaccinate and immunize are used interchangeably - By blocking the spread of bacterium, bacterial toxin, virus, or other microbe at the site of infection or at the target organ, immunity can prevent or lessen the severe symptoms of disease - While protection of individuals from disease is certainly a primary focuse of vaccination, vaccination can also serve to provide protection to a population by lessening the number of susceptible hosts * A more ambitious goal of vaccination is to eradicate a disease; smallpox is an excellent example of how a vaccine can achieve this goal