UWorld Review 5/26

A prospective cohort study was conducted to assess the role of daily alcohol consumption in the occurrence of breast carcinoma. The investigators reported a 5-year relative risk of 1.4 for people who consume alcohol daily compared to those who do not. The 95% confidence interval was 1.02-1.85. Which of the following p-values is most consistent with the results described above?

0.03 - Relative risk (RR) is used in cohort studies to determine how strongly a risk factor (ie, exposure) is associated with an outcome. RR is the risk of an outcome (eg, breast cancer) in the exposed group (eg, individuals who consume alcohol daily) divided by the risk of that outcome in the unexposed group (eg, individuals who do not consume alcohol daily). If the RR = 1.0 (null value), then there is no association between the exposure and the disease. An RR >1.0 indicates that the exposure is associated with increased risk of disease. An RR <1.0 means that the exposure is associated with decreased risk of disease. The RR by itself does not account for the possibility that chance alone is responsible for the results. The 95% confidence interval (CI) and p-value are 2 measures of statistical significance that can help strengthen the findings of a study using RR. For a result to be considered statistically significant, its corresponding CI must NOT contain the null value. When the 95% CI does not include the null value, this gives a corresponding p-value <0.05 and the association between exposure and outcome is considered statistically significant. A p-value <0.05 reflects that there is a very low probability that the result was due to chance alone; formally, the p-value is the probability of observing a given (or more extreme) result due to chance alone assuming that the null hypothesis is true. In this example, the RR is 1.4 with a 95% CI of 1.02-1.85. It can be concluded that daily alcohol consumption is associated with an increased risk of breast carcinoma (RR >1) and that the findings are statistically significant (95% CI does not include the null value of 1.0). Therefore, the expected p-value would be <0.05.

An investigator is studying a line of tumor cells that has developed resistance to several anticancer agents. The tumor cells are exposed to various chemotherapeutic agents, and the intracellular drug concentration is subsequently measured. Following exposure to doxorubicin, the intracellular drug concentration is reduced compared to control cells with no doxorubicin resistance. Western blot analysis shows the tumor cells have increased expression of a specific glycoprotein. This protein most likely has which of the following functions?

ATP-dependent transporter - Tumor cells can develop the ability to resist chemotherapeutic agents, resulting in reduced drug efficacy. The tumor cells in this experiment have acquired resistance to multiple drugs by decreasing intracellular concentration of the drugs, most likely via increased expression of efflux pumps such as P-glycoprotein. P-glycoprotein, encoded by the multidrug resistance 1 gene (MDR1), is a transmembrane protein that functions as an ATP-dependent efflux pump. It is normally highly expressed in intestinal and renal tubular epithelial cells (functions to eliminate foreign compounds from the body) as well as in the endothelium of the vessels that form the blood-brain barrier (prevents penetration of foreign compounds into the CNS). In tumor cells, increased expression of P-glycoprotein can increase the efflux of numerous chemotherapeutic agents from the cytosol, particularly hydrophobic agents (eg, doxorubicin, vincristine). This results in decreased intracellular drug accumulation and is an important mechanism underlying multidrug resistance.

A 55-year-old man comes to the office due to malaise and cough over the past 2 months. He describes yellow sputum production with occasional streaks of blood. The patient smokes a pack of cigarettes daily and has a history of alcohol use disorder with prior episodes of binge drinking. Temperature is 37.1 C (98.8 F). Examination shows poor dentition with dental caries, gingivitis, and enlarged submandibular lymph nodes. Coarse rhonchi are heard during auscultation of the right lung. Chest CT scan reveals an extensive right lung consolidative process with air bronchograms. Bronchoscopy is performed, and a lung biopsy specimen is shown. Which of the following is the most likely diagnosis?

Actinomycosis - Actinomycosis is a slowly progressive disease caused by gram-positive anaerobic bacteria. These organisms typically colonize the mouth, colon, and vagina and can be found in dental caries as well as at the margins of gums in patients with poor dentition. Actinomyces infection most frequently leads to the formation of cervicofacial abscesses, but systemic infection can develop anywhere in the body when the mucosa is disrupted. Pulmonary actinomycosis is usually caused by aspiration, which often leads to lower lobe consolidation with air bronchograms (air-filled bronchi with surrounding alveolar opacification). Patients with alcohol use disorder are at increased risk. Diagnosis is made by identifying the bacteria with unique filamentous, branching patterns and the characteristic sulfur granules, which are formed by calcified mycelial fragments. Sulfur granules grossly appear yellow; however, hematoxylin and eosin staining gives them a basophilic (purple/blue) appearance under light microscopy. Penicillin G is the antibiotic treatment of choice.

A 23-year-old woman comes to the office describing restlessness in her legs and inability to lie or sit still. The patient was diagnosed with schizophrenia a month ago and medication therapy was initiated. Her dose was increased after 2 weeks. She says, "I haven't heard any voices since a few days after the medication was increased." Blood pressure is 140/90 mm Hg and pulse is 90/min. The patient is alert, oriented, fidgety, and anxious. Which of the following is the most likely diagnosis in this patient?

Akathisia - This patient is experiencing akathisia, a type of extrapyramidal side effect associated with antipsychotic treatment. Akathisia ranges from mild subjective feelings of tension to marked physical restlessness (which can be extremely distressing for patients). It typically presents days to weeks after initiating antipsychotic treatment or increasing the dose. Patients describe an inability to sit or stand in one position and may pace frequently or demonstrate other restless behaviors. Treatment options include decreasing the antipsychotic dose (if feasible) or treating with a beta blocker or benzodiazepines.

Investigators assessing the bioavailability of a new drug administer it intravenously (IV) to a volunteer and measure plasma concentrations of the drug over time. After the drug is completely cleared from the volunteer's circulation, the investigators administer the same dose of the drug orally (PO) and again measure plasma concentrations of the drug over time. The data obtained are plotted on a graph. Which of the following is the best determinant of oral bioavailability of this drug?

Area under the PO curve divided by area under the IV curve - Bioavailability refers to the fraction of administered drug that reaches the systemic circulation and is therefore available for eliciting the desired pharmacologic effect. A drug administered by the intravenous (IV) route has 100% bioavailability by definition. For other modes of drug administration (eg, oral [PO], intramuscular [IM], subcutaneous [SQ], transdermal [TD], rectal [PR]), the bioavailability is usually less than 100%. The bioavailability of a drug for a given route of administration can be determined by plotting plasma drug concentrations over time for a given dose administered by both the IV route and the other route being studied (eg, PO). The area under the curve (AUC) of each plot represents the total systemic drug exposure for the given dose and route (Choice A). Bioavailability can then be determined by comparing the AUCs of each curve. In this case, PO bioavailability can be calculated by dividing the AUC of the PO curve by the AUC of the IV curve. In the case of PO administration, bioavailability depends upon the drug's ability to cross the intestinal mucosa and can be influenced by gastric acidity and motility, the presence of food or other drugs in the gut, and first-pass metabolism by the intestine and liver.

A 24-year-old, previously healthy woman comes to the hospital due to a 3-day history of fever, dyspnea, and cough productive of yellow sputum. Temperature is 38.8 C (101.8 F), blood pressure is 110/66 mm Hg, and pulse is 110/min. The patient has bronchial breath sounds and crackles over the right lower lung. Laboratory results are as follows: Hemoglobin 13 g/dL Platelets 350,000/mm3 Leukocytes 54,000/mm3 Neutrophils 65% Band forms 10% Myelocytes 3% Metamyelocytes 1% Lymphocytes 15% The leukocyte alkaline phosphatase test score is elevated. Which of the following is the most likely finding on this patient's peripheral blood smear?

Basophilic oval inclusions in mature neutrophils - This patient most likely has pneumonia with sepsis and an associated leukemoid reaction, a significant leukocytosis (may exceed 50,000/mm3) that occurs in response to an underlying inflammatory condition (eg, severe infection, hemorrhage, solid tumors). Release of colony-stimulating factors and inflammatory mediators into the circulation causes the bone marrow to increase the production of leukocytes, resulting in leukocytosis. Blood smear typically shows numerous mature neutrophils, which may have reactive morphologic features, such as Döhle bodies (blue cytoplasmic inclusions of rough endoplasmic reticulum), toxic granulation, and cytoplasmic vacuoles. Increased neutrophil precursors (eg, bands, metamyelocytes, myelocytes) are also typically present (referred to as "left shift") due to early release from the marrow in response to the increased demand of the inflammatory condition. Assessment of leukocyte alkaline phosphatase (an enzyme found in maturing neutrophils) can be used to distinguish marked leukocytosis due to leukemoid reaction from chronic myeloid leukemia (CML). Values are typically normal or increased in leukemoid reaction; in contrast, they are usually low in CML because the abnormal maturing neutrophils have decreased levels of this enzyme.

A 54-year-old man comes to the office due to new-onset muscle cramps. The patient has a history of hypertension and was started on hydrochlorothiazide 4 weeks ago. Blood pressure is 138/86 mm Hg and pulse is 78/min. Examination shows no abnormalities. Based on his most recent laboratory results, triamterene is added to the current therapy. Which of the following best describes the mechanism of action of this medication?

Blocking renal tubular epithelial sodium channels - Thiazide diuretics lower blood pressure by inhibiting Na+/Cl− cotransporters in the distal convoluted tubules, thereby decreasing reabsorption of Na+ and Cl−. Both thiazides and loop diuretics induce volume loss with subsequent activation of the renin-angiotensin-aldosterone system. Aldosterone increases renal sodium resorption in exchange for potassium by upregulating the synthesis and activity of the following: Epithelial sodium channels: Found on the apical membrane of principal cells, it absorbs Na+ from the tubular lumen Na+/K+-ATPase pump: Located on the basal membrane of principal cells, it extrudes Na+ into the interstitial space in exchange for potassium Because of these effects, increased aldosterone levels commonly result in hypokalemia, which can lead to muscle cramps, weakness, and (when severe) cardiac arrhythmias. Potassium-sparing diuretics may be added to prevent hypokalemia. These weak diuretic medications act in the distal nephron, where they reduce potassium excretion via the following mechanisms: Triamterene and amiloride directly inhibit the epithelial sodium channel, preventing sodium from entering principal cells. This reduces the electrochemical gradient (ie, negative luminal charge) that helps drive potassium secretion. Aldosterone antagonists (ie, spironolactone, eplerenone) directly inhibit the mineralocorticoid receptor, resulting in decreased formation and activity of epithelial sodium channels and Na+/K+-ATPase pumps

A 34-year-old woman comes to the office due to exertional dyspnea. The patient has a history of IgA nephropathy; she received hemodialysis for 2 years before undergoing kidney transplantation last month. Chest x-ray reveals cardiomegaly and pulmonary congestion. Further evaluation determines that her symptoms are likely due to persistence of the arteriovenous fistula that was used for hemodialysis. Which of the following physiologic changes are most likely present in this patient due to the fistula?

Cardiac output ↑ Systemic vascular resistance ↓ Venous return ↑ This patient with dyspnea and chest x-ray showing an enlarged heart and pulmonary edema likely has high-output heart failure due to excessive flow through her arteriovenous fistula. A surgically created arteriovenous fistula forms an enlarged vein that serves as an access point for hemodialysis (which requires a vessel with high blood flow rates); however, if the fistula becomes too large, it can lead to hemodynamic complications. A large arteriovenous fistula allows a high proportion of blood flow to bypass the resistance of the systemic arterioles, causing markedly decreased systemic vascular resistance (SVR) (ie, reduced afterload). Blood passing through the low peripheral resistance returns to the right atrium quickly and easily, resulting in increased venous return (ie, increased preload). Both the reduced afterload and increased preload facilitate increased stroke volume (ie, increased cardiac output). A baroreceptor reflex-mediated increase in contractility and heart rate in response to hypotension may also contribute to increased cardiac output. With excessively large fistulas, the left ventricle becomes unable to keep up with the increased venous return despite a persistent increase in cardiac output; left ventricular diastolic pressure gradually increases, and decompensated heart failure develops. Other common causes of high-output heart failure also involve decreased SVR as the initial disturbance.

A 43-year-old man comes to the emergency department due to fever, chest pain, and hemoptysis. He has a history of a hematologic malignancy for which he recently underwent a cycle of chemotherapy. Laboratory studies show neutropenia due to the chemotherapeutic agents. A nodule with surrounding hypoattenuation is revealed on chest CT. Galactomannan and beta-D-glucan assays are elevated. Sputum cultures grow Aspergillus. The patient is placed on intravenous amphotericin B. During the infusion, he develops headaches, rigors, and hypotension. Over the next few days, there is a decline in renal function attributed to amphotericin. These toxic effects are likely due to binding of the antifungal agent to which of the following?

Cell membrane cholesterol - This patient with febrile neutropenia following chemotherapy has invasive aspergillosis (fever, chest pain, hemoptysis, chest imaging showing nodule with hypoattenuation consistent with "halo sign"). Amphotericin B is a mainstay of treatment for many systemic mycoses. It preferentially binds the ergosterol of fungal cell membranes, leading to fungal cell lysis. This drug is relatively selective as it has a higher affinity for ergosterol (in fungal membranes) than for cholesterol (in human cell membranes). However, it binds cholesterol to a degree, which explains a large number of its adverse effects. Amphotericin B is often administered intravenously. Its main toxicities include the following: Acute infusion-related reactions, such as fever, chills, rigors, and hypotension, can occur. These are common and are seen most frequently during initial infusions (often diminish with subsequent infusions). Premedication with antipyretics and antihistamines can lessen the severity of these effects. Dose-dependent nephrotoxicity can result from a drug-induced decrease in the glomerular filtration rate. Permanent loss of renal function is thought to be related to the cumulative total dose. Renal function (eg, creatinine) should be closely monitored in patients undergoing treatment with amphotericin. Concomitant administration of other nephrotoxic drugs (eg, aminoglycosides, cyclosporine) should be avoided. Significant electrolyte abnormalities (hypomagnesemia and hypokalemia) can develop. These effects occur in the majority of patients within the first week of therapy. Electrolytes should be monitored daily and replaced as needed. Anemia occurs due to suppression of renal erythropoietin synthesis. This effect may be severe in patients with HIV who are taking zidovudine (which also suppresses bone marrow function). Thrombophlebitis can be seen at the site of injection.

A 68-year-old man comes to the office due to thigh and leg pain that worsens with exertion. He is unable to walk through the local mall with his wife without discomfort. Past medical history is significant for hypertension and diabetes mellitus. The patient smokes 2 packs of cigarettes a day and consumes alcohol occasionally. Physical examination of the extremities shows weak dorsalis pedis pulses in both feet. Further evaluation confirms moderate peripheral arterial disease involving both lower extremities. Which of the following drugs would best provide symptomatic improvement due to direct dilation of arteries and inhibition of platelet aggregation?

Cilostazol - Several molecules, including thrombin, adenosine diphosphate, and thromboxane A2, activate platelets by acting on cell surface receptors. However, interference with post-receptor signaling can alter platelet function. In particular, cyclic adenosine monophosphate (cAMP) activates a family of enzymes known as the cAMP-dependent protein kinases, or protein kinase A, and leads to inhibition of platelet aggregation. Agents that increase intra-platelet cAMP levels decrease platelet aggregation by preventing platelet shape change and granule release. Cilostazol reduces platelet activation by inhibiting platelet phosphodiesterase, the enzyme responsible for the breakdown of cAMP. It is also a direct arterial vasodilator. The net effect is a decrease in claudication symptoms and an increase in pain-free walking distances in patients with peripheral arterial disease (PAD). Patients with PAD should be initiated on a graded exercise program, which has also been shown to improve symptoms.

A 32-year-old woman comes to the office due to a small amount of malodorous vaginal discharge. She is sexually active with a male partner and uses condoms sporadically. The patient also requests testing for all sexually transmitted diseases because she is unsure if her partner is monogamous. She drinks a glass of wine every night with dinner and has had an abnormal Pap test in the past. Speculum examination reveals thin, gray discharge. Wet mount microscopy of the discharge shows large, atypical vaginal epithelial cells and no protozoa. Application of potassium hydroxide solution to the discharge yields a strong odor. Which of the following is the best treatment option for this patient?

Clindamycin - This patient has bacterial vaginosis (BV), an alteration in the normal vaginal flora associated with loss of lactobacilli and overgrowth of anaerobes, particularly the gram-variable rod Gardnerella vaginalis. Although BV is not a sexually transmitted infection, it is associated with sexual activity (due to alterations of the vaginal flora from semen or contraceptives [eg, spermicide]). Patients with BV commonly have a thin, gray or clear malodorous vaginal discharge. The discharge's odor becomes more prominent when potassium hydroxide (KOH) is added to a sample (whiff test) because of the volatilization of amines produced by G vaginalis and other anaerobes. Clue cells on wet mount microscopy are also characteristic. Clindamycin and metronidazole are effective treatments for BV. Clindamycin is a bacteriostatic drug that inhibits protein translation by binding to the 50s ribosomal subunit. Metronidazole is bactericidal and damages the DNA of anaerobes; it is typically avoided with concurrent use of alcohol due to a disulfiram-like reaction (eg, vomiting, flushing).

A 52-year-old man is brought to the emergency department due to worsening right leg pain, fever, and confusion. The patient injured his leg while operating a motorized watercraft on the ocean near Florida 2 days ago. Temperature is 38.9 C (102 F), blood pressure is 90/50 mm Hg, and pulse is 120/min. The patient is lethargic and diaphoretic. Physical examination reveals a small laceration on the dorsum of the right foot with surrounding edema, erythema, and several hemorrhagic bullae. Leukocyte count and serum lactic acid levels are elevated. Intravenous fluids and empiric antibiotics are administered, and surgical debridement of the wound is performed. Blood and wound cultures yield curved gram-negative rods. Which of the following is the greatest risk factor for this patient's infection?

Condition causing iron overload - Vibrio vulnificus is a curved, gram-negative, free-living bacterium that grows in brackish coastal water and marine environments. This bacterium is found in greatest concentrations in the summer months, comprising as much as 8% of the total bacteria in some areas. V vulnificus infections are primarily acquired through the consumption of raw oysters (which concentrate the bacterium) or wound contamination during recreational water activities or the handling of raw seafood. Most patients who become ill have liver disease (eg, alcohol-associated cirrhosis, viral hepatitis); those with iron overload (eg, hemochromatosis) are at particularly high risk as free iron acts as an exponential growth catalyst for the bacterium. Healthy patients with V vulnificus wound contamination usually develop a mild cellulitis, but those with iron overload or liver disease are at high risk for rapidly progressive necrotizing fasciitis with hemorrhagic, bullous lesions and septic shock (eg, hypotension, elevated lactic acid level). In these patients, urgent antibiotics, surgery, and blood pressure support are usually required to prevent death.

A 5-year-old boy is brought to the office due to concerns about his speech and motor skills. The patient has a history of speech delay, and his parents say that his speech has become more slurred lately. He also has an unsteady, staggering gait that has progressively worsened over the past year. In addition, the mother states that the patient's eyes and head "do not move smoothly" when he looks at moving objects. Medical history is significant for recurrent ear and pulmonary infections. Vital signs are normal. Physical examination reveals numerous superficial nests of distended capillaries on the face and ears that blanch with pressure. This patient's condition is most likely due to a genetic defect affecting which of the following processes?

DNA break repair - This patient has facial telangiectasias, recurrent infections, and signs of cerebellar dysfunction (eg, unsteady gait, slurred speech), findings characteristic of ataxia-telangiectasia (AT). This autosomal recessive condition is caused by a defect in the ATM (ataxia-telangiectasia mutated) gene. ATM kinase normally plays a role in the detection of DNA damage (eg, oxidative injury) through phosphorylation of various proteins, which then halt the cell cycle to allow for DNA break repair. Without this surveillance mechanism, DNA is susceptible to ionizing radiation and prone to chromosomal breakage; accumulation of DNA mutations also increases the risk of malignant transformation. Neurons are particularly prone to oxidative stress, and the first manifestations of AT are typically due to cerebellar degeneration. Unsteady gait progressively worsens in early childhood, and patients often display delayed and slurred (dysarthria) speech. Impaired head/eye coordination (oculomotor apraxia) is also common. In addition, defective DNA rearrangement in developing lymphocytes often results in cellular and humoral immunodeficiency and recurrent sinopulmonary infections. Diagnosis is often delayed until characteristic telangiectasias, or superficial nests of dilated blood vessels, appear on the face and bulbar conjunctiva at age 3-5.

A 34-year-old woman comes to the office due to vague abdominal pain over the past several months. She has no significant past medical history. The patient does not use tobacco or alcohol. Temperature is 36.7 C (98.1 F). On physical examination, right upper quadrant fullness is present. Abdominal imaging reveals a dense liver mass. Angiography shows a well-demarcated, highly vascularized tumor surrounded by normal liver parenchyma. Which of the following substances most likely contributed the most to blood vessel development in this patient's tumor?

Fibroblast growth factor - This patient has a highly vascularized liver tumor, possibly a benign hepatic hemangioma. Many cases are discovered incidentally. Angiogenesis (blood vessel formation) is predominantly driven by the following 2 substances: Vascular endothelial growth factor (VEGF): VEGF stimulates angiogenesis in a variety of tissues (normal, chronically inflamed, healing, or neoplastic). As VEGF increases endothelial cell motility and proliferation, new capillaries begin to sprout. Fibroblast growth factor (FGF): FGF-2 is produced by a wide range of cells and is involved in endothelial cell proliferation, migration, and differentiation. FGF-2 also appears to play an important role in embryogenesis by stimulating angioblast production. As a group, FGFs not only contribute to angiogenesis, but also to embryonic development, hematopoiesis, and wound repair (by recruiting macrophages, fibroblasts, and endothelial cells to damaged tissues). However, the laminin in basement membranes may pose a physical barrier to the sprouting of new blood vessels.

A 68-year-old male presents to your office complaining of difficulty urinating. His past medical history is significant for prostate cancer treated with radiation therapy one year ago. Ultrasonography reveals bilateral dilation of the ureters and renal calyces. If related to the previous therapy, which of the following is the most likely cause of this patient's current condition?

Fibrosis - Radiotherapy has applications as primary, adjuvant, or more commonly palliative therapy for many types of cancer. Tumor sensitivity to radiation depends on the rate of cell turnover, with rapidly growing tumors being more sensitive. In the same way, rapidly dividing normal body tissues such as blood cell precursors, epithelial surfaces in the skin, GI tract, and urinary tract, and the gonads (gametes) are also at risk for damage. Fibrosis and strictures due to diffuse scarring of the damaged tissues often occurs as a late complication of radiotherapy for prostate cancer, and may lead to obstructive uropathy.

A 64-year-old man comes to the office due to 2 days of dysuria, urinary frequency, and urgency. He recently underwent a cystoscopy for evaluation of hematuria. The patient has a history of hypertension, type 2 diabetes mellitus, and 30 pack-years of cigarette smoking. His temperature is 38.2 C (100.8 F). On examination, there is suprapubic tenderness on deep palpation but no costovertebral angle tenderness. Urinalysis findings are as follows: Leukocyte esterase positive Nitrites negative Bacteria many White blood cells 20-30/hpf Red blood cells many/hpf Midstream urine culture grows gram-positive cocci in chains with growth >100,000 colony-forming units/mL. The organism responsible for this patient's condition is most likely to demonstrate which of the following?

Gamma hemolysis on blood agar - This patient who recently underwent a genitourinary procedure (cystoscopy) has a urinary tract infection caused by Enterococcus. This organism has a morphology of gram-positive cocci in pairs and chains and, when grown on blood agar, reveals no hemolysis (gamma hemolysis). Other characteristics of enterococci include pyrrolidonyl arylamidase (PYR) positivity and ability to grow in bile and in 6.5% sodium chloride. They are unable to convert nitrates to nitrites, explaining this patient's negative result on urinalysis nitrite. Enterococci are part of the normal intestinal flora of humans and animals. Enterococcus faecalis and E faecium are the most prevalent species cultured from humans and can cause urinary tract infection, bacteremia/endocarditis, wound infection, or intraabdominal or pelvic infection in the nosocomial setting. Enterococci have both intrinsic (beta-lactams, macrolides, aminoglycosides, trimethoprim-sulfamethoxazole) and acquired (vancomycin) resistance to antibiotics, making them important nosocomial pathogens.

A 46-year-old woman being evaluated for irregular vaginal bleeding is found to have invasive cervical carcinoma. She undergoes total abdominal hysterectomy and bilateral salpingo-oophorectomy. Pelvic lymphadenectomy was also performed, during which several enlarged nodes around the pelvic vessels were resected. A week after the surgery, the patient begins to experience left-sided flank pain that radiates to the groin. Her temperature is 36.1 C (97 F), blood pressure is 120/70 mm Hg, and pulse is 84/min. On physical examination, there is a ballotable left flank mass. Which of the following most likely accounts for this physical examination finding?

Hydronephrosis - Flank pain radiating to the groin with a ballotable (ie, palpatable between both hands) flank mass that develops within a week of pelvic surgery suggests ureteric obstruction. The ureter runs in close proximity to the pelvic vessels. It courses anterior to the iliac vessels (area of resection of the pelvic nodes, which drain the uterus and cervix) and just posterior to the uterine artery near the lateral fornix of the vagina. It is vulnerable to injury during pelvic surgery, such as that involved in hysterectomy with pelvic lymphadenectomy. Unintentional ureteral ligation causes obstruction with hydronephrosis and flank pain due to distension of the ureter and renal pelvis. Urine output and serum creatinine remain within normal limits in most individuals with unilateral obstruction because the contralateral kidney functions normally and compensates for decreased functioning of the affected kidney.

A 58-year-old man comes to the office due to fatigue, decreased appetite, muscle cramps, and nausea. The patient has chronic kidney disease resulting from primary focal segmental glomerulosclerosis. His current medications include a vitamin D supplement. While his blood pressure is being obtained, the patient develops carpal spasm. Bilateral lower extremity pedal edema is noted. Laboratory evaluation shows a blood urea nitrogen level of 120 mg/dL, serum creatinine level of 10 mg/dL, and serum calcium level of 6 mg/dL. Which of the following is most likely contributing to this patient's carpal spasm?

Hyperphosphatemia - This patient with chronic kidney disease (CKD) has developed carpal spasm secondary to hypocalcemia. In CKD, reduced filtration and excretion of phosphorus causes hyperphosphatemia, which induces hypocalcemia through the following mechanisms: Released phosphate binds to free calcium and precipitates in soft tissues (which, over the long term, can lead to vascular calcification and stiffness) Increased serum phosphate triggers the release of fibroblast growth factor 23 from bone, which acts to lower phosphate levels in part by inhibiting renal expression of 1-alpha hydroxylase. This reduces production of 1,25-hydroxyvitamin D (calcitriol), leading to reduced intestinal calcium absorption Hypocalcemia is also worsened by the progressive loss of functioning renal tissue in CKD, which further reduces calcitriol synthesis. Hypocalcemia can cause alterations in cellular membrane potentials and neuromuscular excitability. Manifestations include muscle cramps, Chvostek (facial twitching elicited by tapping on the facial nerve) and Trousseau (carpal spasm triggered by inflation of a blood pressure cuff around the arm) signs, hyperreflexia, QTc prolongation, and seizures.

A 45-year-old woman is brought to the hospital after she collapsed during an airshow on a hot summer day. The patient has a history of fibromyalgia and takes amitriptyline. Temperature is 40.5 C (104.9 F), blood pressure is 90/60 mm Hg, pulse is 110/min, and respirations are 22/min. The skin is warm and red. She is disoriented. Neurologic examination shows no focal findings. If this patient's medication contributed to her current condition, which of the following mechanisms is most likely responsible?

Impaired dissipation of body heat - This patient developed severe hyperthermia and encephalopathy while spending time outside on a hot summer day. This presentation is suggestive of nonexertional heat stroke (NHS), a life-threatening multisystem disorder characterized by hyperthermia (typically >40 C [104 F]) associated with CNS dysfunction (eg, encephalopathy, syncope). Other classic manifestations of heat stroke include tachycardia, tachypnea, hypotension, flushing, and end-organ dysfunction (eg, pulmonary edema, renal/hepatic failure). Diaphoresis may or may not be present on examination, depending on hydration status and sweat gland function. The body normally maintains a core temperature of ~37 C (98.6 F) through multiple thermoregulatory mechanisms controlled by the anterior hypothalamus; excessive temperature stimulates diaphoresis, peripheral vasodilation, and behavioral changes (eg, seeking shade). However, certain medications can interfere with these processes, thereby promoting hyperthermia. These medications include the following: Anticholinergics (eg, amitriptyline, scopolamine) inhibit diaphoresis, limiting the body's primary mechanism of heat dissipation. Sympathomimetics (eg, amphetamines, cocaine) impair peripheral vasodilation, limiting heat transfer to the skin. Dopaminergic antagonists (eg, chlorpromazine, haloperidol) disrupt hypothalamic thermoregulation, likely by blocking dopamine transmission in the hypothalamus. Diuretics (eg, furosemide) and beta blockers (eg, metoprolol) limit the cardiac response to heat stress by reducing blood volume or heart rate, thereby decreasing blood flow to the skin.

A 35-year-old man comes to the office for evaluation of an enlarged left testis. He also reports decreased libido and erectile potency for the last 2 months. The patient has no chronic medical conditions and takes no medications. Physical examination is notable for significant enlargement of the left testis and bilateral gynecomastia. His other secondary sexual characteristics are normal. Serum β-hCG is markedly elevated and serum TSH is normal. Scrotal ultrasound reveals a 3.1-cm, irregular testicular mass with cystic areas. Which of the following is the most likely cause of this patient's gynecomastia?

Increased Leydig cell aromatase activity - Gynecomastia is abnormal growth of breast tissue in males. It is generally due to an increased ratio of estrogens (which cause hyperplasia of breast ductal epithelium and increased fibrosis of stromal tissues) to androgens (which have an inhibitory effect on breast development). In addition to gynecomastia, this patient has hypogonadal symptoms (eg, decreased libido, erectile dysfunction) that suggest decreased testicular androgen production. In light of the large testicular mass and elevated β-hCG level, this likely represents an hCG-secreting germ cell tumor of the testis. Excessive secretion of hCG by testicular germ cell tumors suppresses testosterone production in Leydig cells while increasing aromatase activity and conversion of testosterone to estradiol; the resulting increase in the estrogen/androgen ratio can cause gynecomastia.

A 31-year-old woman comes to the emergency department due to worsening right upper quadrant pain, fever, nausea, and vomiting for a day. The pain increases with deep inspiration. Other medical conditions include uterine fibroids and sickle cell anemia. The patient does not use tobacco, alcohol, or illicit drugs. Temperature is 38.6 C (101.5 F), blood pressure is 120/70 mm Hg, and pulse is 102/min. BMI is 24 kg/m2. On examination, the patient appears uncomfortable because of the pain; there is no jaundice. Tenderness and guarding are present over the right upper quadrant. Bowel sounds are decreased. Hemoglobin is 10.1 g/dL and white blood cell count is 18,000/mm3 with 7% band forms. Abdominal ultrasound shows evidence of cholelithiasis and gallbladder wall thickening. Gross inspection of the specimen obtained during laparoscopic cholecystectomy is shown. Which of the following is most likely responsible for this patient's symptoms?

Increased efflux of bilirubin into bile - This patient with fever, right upper quadrant pain, and leukocytosis has acute cholecystitis. Cholecystitis is inflammation of the gallbladder that usually occurs when gallstones obstruct the cystic duct. Gallstones form due to supersaturation of bile constituents (eg, cholesterol, bilirubin), which then crystalize out of solution with other bile components (eg, mucin, calcium, proteins) to produce stones. Black gallstones, as seen in this patient, form due to the supersaturation of bilirubin, which precipitates with calcium to form multiple small calcium bilirubinate stones. Bilirubin supersaturation occurs through the following mechanisms: Increased bilirubin production: Chronic hemolysis, as seen in sickle cell anemia, hereditary spherocytosis, and thalassemia, increases circulating levels of free bilirubin, which is taken up by the liver and excreted into bile. Altered enterohepatic circulation of bilirubin: Ileal disease (eg, Crohn disease) or resection allows bile acids, which are normally reabsorbed in the ileum, to spill into the colon. There, bile acids solubilize unconjugated bilirubin, allowing its reabsorption and concentration within the bile. This patient with sickle cell anemia most likely has chronic hemolysis, which has increased bilirubin efflux into the bile, promoting formation of black stones.

A 68-year-old woman is brought to the emergency department due to confusion and lower extremity weakness. The symptoms began 2 days ago along with fever, headache, malaise, and myalgias. Today, the patient was noted to be confused and had difficulty ambulating due to left lower extremity weakness. The patient has a history of lymphoma in remission, hypertension, and type 2 diabetes mellitus. She drinks alcohol socially but does not use tobacco or illicit drugs. She is visiting her family in Texas for the summer and has never traveled outside the United States. Temperature is 38.3 C (101 F), blood pressure is 130/70 mm Hg, and pulse is 96/min. The patient is oriented to place and person only and has a coarse hand tremor. There is flaccid paralysis of the left lower extremity with preserved sensation. CT scan of the head shows no abnormalities. Lumbar puncture is performed, and cerebrospinal fluid analysis shows lymphocytic pleocytosis and elevated protein. Cerebrospinal fluid polymerase chain reaction testing yields viral RNA. The agent infecting this patient most likely uses which of the following modes of transmission?

Insect bite - This patient has acute confusion associated with fever and asymmetric lower extremity paralysis, consistent with neuroinvasive West Nile virus (WNV) infection. WNV is a positive-sense, single-strand RNA flavivirus transmitted by female mosquitoes (Culex spp), most commonly in the summer in warmer regions (eg, southern United States, Latin America, Africa). Most WNV infections are asymptomatic or present with a flu-like illness (ie, West Nile fever: fever, headache, myalgias), often with a maculopapular or morbilliform rash on the back and chest. Neuroinvasive infection is an uncommon complication of WNV but has a 10% fatality rate. It occurs most commonly in older patients and those with a history of malignancy or organ transplant, and is characterized by meningitis (ie, headache, meningismus) and/or encephalitis (altered mental status). The presence of acute-onset asymmetric flaccid paralysis is highly suggestive of WNV, particularly if the patient demonstrates concurrent parkinsonian features (eg, rigidity, bradykinesia, tremor, postural instability). Diagnosis can be made when compatible clinical findings are associated with positive cerebrospinal fluid anti-WNV antibodies (polymerase chain reaction testing often not needed).

A 64-year-old man comes to the clinic due to several weeks of persistent cough, fever, and weight loss. He smokes a pack of cigarettes daily and drinks 10-12 beers on weekends. Chest x-ray reveals an infiltrate in the left upper lobe. The patient is prescribed broad-spectrum antibiotic therapy for both aspiration and community-acquired pneumonia, but his symptoms worsen despite taking the medication as prescribed. Sputum Gram stain does not reveal any organisms. Lung biopsy findings are shown. Which of the following substances is most important for driving the development of this patient's observed microscopic lesion?

Interferon-gamma - This patient has cough, fever, weight loss, and an upper lobe lesion on chest x-ray, raising strong suspicion for active pulmonary tuberculosis. Mycobacterium tuberculosis cannot be visualized on Gram stain due to the high lipid content (mycolic acid) of its cell wall. Most cases are diagnosed by acid-fast sputum testing and culture, but tissue microscopy typically shows granulomas characterized by epithelioid histiocytes and multinucleated Langhans giant cells. Granulomas often form after tissue macrophages encounter pathogens or substances that cannot be easily digested or removed. M tuberculosis can evade intracellular killing by macrophages and reproduce within phagolysosomes. Infected macrophages present mycobacterial antigens to naïve CD4 helper T cells in pulmonary lymph nodes and secrete IL-12, which induces activated T helper cells to differentiate into T helper subtype 1 (Th1) cells. Proliferating Th1 cells migrate to sites of infection, where they release interferon-gamma, which activates macrophages, improves intracellular killing of ingested mycobacteria, and recruits additional macrophages by increasing production of tumor necrosis factor-alpha. Activated macrophages can also limit the spread of mycobacteria by differentiating into epithelioid and giant cells that surround residual foci of mycobacteria, trapping them inside the necrotic, cheese-like area of a caseating granuloma.

A 21-year-old man comes to the emergency department after suffering an injury during a football game. He was falling to the ground when he was struck forcefully from behind by the helmet of an opposing player. The patient was able to ambulate after the injury but has since had severe pain worsened by deep breaths. His blood pressure is 110/65 mm Hg, pulse is 110/min, and respirations are 16/min. On examination, there is bruising and tenderness over the left posterior chest wall. There is normal spinal range of motion and no midline tenderness. Gait and lower extremity neurologic examination are normal. Imaging studies reveal a fracture of the left 12th rib. Which of the following structures is most likely to be lacerated by the fractured bone?

Left kidney - The first 7 rib pairs are considered "true" ribs because their costal cartilage attaches directly to the sternum; the cartilage of the lower 5 pairs does not, and they are considered "false" ribs. Of these, the cartilage of ribs 8-10 attaches to the costal cartilage of the upper ribs. The 11th and 12th ribs are "floating" ribs, meaning that they are not bound to the anterior rib cage by cartilage. The left 12th rib overlies the parietal pleura medially and the kidney laterally. For this reason, the distal tip of the left 12th rib can be displaced into the retroperitoneum when fractured, lacerating the left kidney.

Scientists studying the principles behind oxygen-hemoglobin dissociation have discovered a way to successfully separate hemoglobin tetramers into individual alpha and beta subunits. During an experiment, a solution is created that contains only monomeric beta-hemoglobin subunits under physiologic conditions. If measured, the oxygen dissociation curve of the dissolved beta subunits will most likely resemble which of the following lines?

Major left shift with hyperbolic curve - Hemeproteins such as hemoglobin and myoglobin contain heme groups that are used to reversibly bind oxygen for transportation and storage. Hemoglobin A (the major form of hemoglobin in adults) is a tetramer consisting of 2 alpha and 2 beta chains. Each hemoglobin subunit is associated with a heme moiety, so each hemoglobin molecule has 4 heme groups. After binding to 1 oxygen molecule, the oxygen affinity of other heme molecules increases; this heme-heme interaction is responsible for the characteristic sigmoid shape of the oxygen-hemoglobin dissociation curve. In contrast to hemoglobin, myoglobin is a monomeric protein and the primary oxygen-storing protein in skeletal and cardiac muscle tissue; it is only found in the bloodstream after muscle injury. The partial pressure of oxygen at which 50% of myoglobin molecules are oxygen saturated (P50) is only 1 mm Hg, which is much lower than the P50 of hemoglobin (26 mm Hg). Myoglobin also has only a single heme group and so does not experience heme-heme interactions; therefore, its oxygen-dissociation curve is hyperbolic. The secondary and tertiary structures of myoglobin and the hemoglobin beta subunit are almost identical (the α-subunits are also very similar to myoglobin). Because individual hemoglobin subunits are structurally similar to myoglobin, their oxygen-binding behavior is also similar. That is, if a hemoglobin molecule is dissociated, the individual subunits will have a hyperbolic oxygen-dissociation curve

A 32-year-old woman comes to the office due to lower back pain after lifting heavy furniture a week ago. She recently moved to the area with her boyfriend, who is starting a new job. Physical examination shows mild paraspinal muscle tenderness. There is no radiation of pain on either side during the straight-leg raise test, and no neurologic deficits are noted in the lower extremities. However, multiple bruises in various stages of healing are noted on her abdomen and back. When the patient is asked about the bruising, she says, "It's nothing. I'm just really clumsy and bump into things." The patient provides brief responses and avoids eye contact throughout the evaluation. Which of the following is the most appropriate statement?

Moving to a new city can be stressful. How are things going at home? - This patient with multiple bruises in various stages of healing is likely affected by intimate partner violence (IPV), which is any type of harm (eg, physical, psychologic, sexual) committed by a partner. IPV particularly affects women of childbearing age, with increased incidence during stressful life events (eg, recent move, new job). However, patients often underreport IPV due to shame or fear of retribution; therefore, a high degree of clinical suspicion should be maintained. Physicians should be alert to clues such as multiple injuries with unlikely explanations (eg, "I'm clumsy and bump into things") and signs of fearfulness or avoidance (eg, brief responses, avoidance of eye contact). Patients with active IPV are often less forthcoming and reluctant to speak; therefore, the initial approach should avoid direct questioning and first necessitate establishing rapport with empathic validation (eg, "Moving to a new city can be stressful"). This can then be followed by indirect questioning to address the concern (eg, "How are things going at home?"). This approach is a subtler way of introducing the topic of IPV and can decrease patient hesitation while avoiding defensiveness or denial.

A 6-year-old African American boy is brought to the physician because of easy fatigability. Physical examination reveals splenomegaly, and his complete blood count shows mild anemia. Hemoglobin electrophoresis is performed at alkaline pH on a cellulose acetate strip. Findings for the patient are shown below compared to individuals with normal hemoglobin and known sickle cell disease. Which of the following is the most likely cause of this patient's condition?

Missense mutation - Hemoglobin electrophoresis is used to assess for different forms of hemoglobin in patients with suspected hemoglobinopathy. Normal hemoglobin consists primarily of hemoglobin A (HbA), which migrates rapidly toward the positive electrode (anode) because of its negative charge. Hemoglobin S (HbS) is an abnormal type of hemoglobin in which a nonpolar amino acid (valine) replaces a negatively charged amino acid (glutamate) in the beta globin chain. This amino acid replacement decreases the negative charge on the HbS molecule, which causes HbS to move more slowly toward the anode. Similarly, hemoglobin C (HbC) has a glutamate residue replaced by lysine in the beta globin chain. Because lysine is a positively charged amino acid, HbC has even less total negative charge than HbS and moves even more slowly toward the anode. Both HbC and HbS result from missense mutations, a type of mutation in which a single base substitution results in a codon that codes for a different amino acid. Patients with sickle cell disease have HbS mutations in both beta chains; those with HbC disease have HbC mutations involving both beta chains. Patients with hemoglobin SC disease have 1 HbS allele and 1 HbC allele and will have 2 hemoglobin bands on electrophoresis. This patient's electrophoresis results show a single band that migrates less than the HbA and HbS bands, meaning that he has HbC disease. Patients with HbC disease are typically asymptomatic and often have mild hemolytic anemia and splenomegaly.

A 30-year-old man comes to the office with a neck lump. The patient is otherwise asymptomatic and discovered the nodule incidentally while showering. His medical history is significant for a recently diagnosed pheochromocytoma, which was successfully removed. The patient's father died of thyroid cancer in his 30s. An ultrasound reveals a hypoechoic 3-cm nodule in the right lobe of the thyroid gland. Fine-needle biopsy of the nodule is consistent with a subtype of thyroid cancer. The patient undergoes total thyroidectomy with central neck dissection. Which of the following is the most likely histological finding?

Nests of polygonal cells with Congo red-positive deposits - This patient has a personal history of pheochromocytoma and a family history of thyroid cancer. His new thyroid malignancy therefore raises suspicion for multiple endocrine neoplasia type 2 (MEN2), which is characterized by: Medullary thyroid cancer Pheochromocytoma Either parathyroid hyperplasia (type 2A) or marfanoid habitus and mucosal neuromas (type 2B) Approximately 20% of medullary thyroid cancers are familial, occurring as part of MEN2 or familial medullary thyroid cancer syndrome due to germ-line mutations of the RET proto-oncogene. Medullary thyroid cancer is a neuroendocrine tumor that arises from parafollicular calcitonin-secreting C cells. Nests or sheets of polygonal or spindle-shaped cells with extracellular amyloid deposits are seen microscopically. These amyloid deposits are derived from calcitonin secreted by the neoplastic C cells and stain with Congo red. Despite overproduction of calcitonin, hypocalcemia is not a prominent feature.

An 86-year-old woman is hospitalized for a urinary tract infection due to Escherichia coli and is being treated with ceftriaxone. She has a history of advanced dementia, coronary artery disease, and congestive heart failure. On the fifth day of hospitalization, she seems agitated. The nurse also reports that the patient had 3 episodes of diarrhea the previous night. Her temperature is 38.3 C (101 F). In addition to appropriate hand hygiene, which of the following equipment is necessary before examining this patient?

Nonsterile gloves and gown - This hospitalized patient's fever and diarrhea a few days after antibiotic initiation are concerning for Clostridium difficile infection. All hospitalized patients require standard precautions, including handwashing before and after patient contact, proper disposal of cleaning instruments and linens, and occasional use of gowns and gloves as required (eg, contact with body fluids). However, cases of suspected or proven C difficile infection require additional contact precautions, including handwashing with soap and water (alcohol-based hand sanitizers do not kill the spores), gown for any patient contact, and nonsterile gloves that should be changed after contact with contaminated secretions. Gloves alone would not be sufficient. In addition, a dedicated stethoscope and blood pressure cuff should be left in the patient's room.

A researcher is interested in studying whether there is an association between neural tube defects and use of acetaminophen during the first 3 months of pregnancy. He randomly chooses a group of women who have just delivered babies with neural tube defects, and a second group of women who delivered apparently healthy babies. These 2 groups were then asked about their use of acetaminophen during the first 3 months of pregnancy. Which of the following measures of association are the investigators most likely to report?

Odds ratio - This scenario describes a typical case-control study design. People with the disease of interest (ie, cases [women who have just delivered babies with neural tube defects]) and people without this disease (ie, controls [women who delivered apparently healthy babies]) are asked about previous exposure to the risk factor being studied (eg, acetaminophen use during the first 3 months of pregnancy). The main measure of association is the odds ratio (OR). The OR can be calculated as follows: OR = (odds of exposure in cases) / (odds of exposure in controls)

A 31-year-old woman comes to the office for a yearly checkup. The patient has no medical conditions but expresses dissatisfaction with her appearance and wishes she could lose weight more easily. She reports occasional constipation and fatigue. The patient exercises daily and drinks 1 or 2 glasses of wine 2-3 times a week when socializing with friends. Weight is 58.1 kg (128 lb) and height is 157.5 cm (5 ft 2 in). BMI is 23.4 kg/m2. Routine laboratory evaluation shows a potassium level of 3.1 mEq/L. Physical examination is most likely to show which of the following abnormalities?

Parotid gland enlargement - Hypokalemia in an otherwise healthy young adult with a normal BMI and preoccupation with body shape and weight is concerning for self-induced vomiting associated with bulimia nervosa (BN). BN is characterized by repeated episodes of binge eating followed by compensatory behaviors (eg, vomiting, laxative use, fasting, excessive exercise) to prevent weight gain. Because patients may not be forthcoming about their eating behavior due to embarrassment, physical examination and laboratory assessment can assist in making the diagnosis. Painless bilateral parotid gland enlargement due to repetitive vomiting is a common finding. Other signs of BN include tachycardia, hypotension, dry skin, calluses or scarring on the dorsum of the hand (Russell sign), and erosion of dental enamel. Common electrolyte abnormalities in BN include hypokalemia and metabolic alkalosis.

A 24-year-old pregnant woman comes to the emergency department in active labor at full term. The patient has a history of HIV from injection drug use. She is not adherent with antiretroviral therapy and has had no recent testing of CD4 count or plasma viral load. Physical examination shows regular uterine contractions, ruptured amniotic membranes, and a fully dilated cervix. A decision is made to continue with the vaginal delivery due to advanced labor. Intravenous zidovudine is administered to the patient during the delivery and to the infant immediately after birth. This medication helps decrease the risk of perinatal transmission by inhibiting which of the following components of viral genome replication?

Phosphodiester bond formation - HIV is a single-stranded RNA virus that is converted into cDNA by the HIV enzyme reverse transcriptase. This enzyme grows DNA by adding nucleotides to the terminal 3′-hydroxyl group using a 3′-5′ phosphodiester bond. Nucleoside reverse transcriptase inhibitors (NRTIs) such as zidovudine block this step in viral replication. This class of medications is composed of nucleoside/nucleotide analogues that do not have a 3′-hydroxyl group. When reverse transcriptase incorporates an NRTI into a growing DNA strand, it results in chain termination because no 3′-hydroxyl group is available to add additional base pairs. Zidovudine (ZDT) was the first approved HIV medication but is now used primarily to prevent maternal to fetal transmission of HIV during labor and delivery. It is a thymidine analogue that contains an azido group in place of the hydroxyl group usually found at the 3′ end of thymidine.

A 2-week-old girl is brought to her primary care provider for a routine visit. The patient was born by normal spontaneous vaginal delivery at 39 weeks gestation. The mother is breastfeeding exclusively, and the infant has regained her birth weight. Newborn screening results from hemoglobin electrophoresis are as follows: Hemoglobin F 70% Hemoglobin A 20% Hemoglobin S 10% The patient's mother has sickle cell trait, and a maternal cousin has sickle cell anemia. Examination shows a well-appearing infant with no pallor or splenomegaly. Which of the following is most likely true about this patient?

She has relative protection from Plasmodium falciparum - This patient's hemoglobin electrophoresis from her newborn screen is most consistent with sickle cell trait. At birth, infants who are heterozygous for sickle cell trait typically have the greatest amount of fetal hemoglobin (Hb F), followed by hemoglobin A (Hb A), and the smallest amount of hemoglobin S (Hb S). Hb A continues to be higher than Hb S throughout the lifetime of these patients as Hb F naturally declines, offering protection from sickle cell anemia, aplastic crises, and splenic sequestration. Patients with sickle cell trait are usually asymptomatic with normal hemoglobin level, reticulocyte count, and red blood cell (RBC) indices. However, they may develop hematuria, priapism, and increased incidence of urinary tract infections. Splenic infarction at high altitudes has also been reported. Patients with sickle cell trait have relative protection from Plasmodium falciparum (malaria), resulting in lower rates of severe malaria and hospitalization than seen in the general population. Possible mechanisms include increased sickling of parasitized sickle cell trait RBCs and accelerated removal of these cells by the splenic monocyte-macrophage system. These patients are not immune to malaria, however, and those visiting malaria-endemic areas should still receive prophylaxis.

A 38-year-old man comes to the office with abdominal discomfort and loose stools over the past year. He has also lost 10 kg (22 lb) despite having a normal appetite. The patient eats a balanced diet that includes a variety of fruits and vegetables, meats, whole grains, and dairy products. He has had no international travel, works indoors as an office manager, and has no sick contacts. Medical history is insignificant and the patient takes no medications. The patient drinks alcohol socially and does not use tobacco. Vital signs and physical examination are normal. Serum chemistry panel, complete blood count, and thyroid function tests are normal. Which of the following is the best next step for assessing for impaired nutrient absorption in this patient?

Stool microscopy with Sudan III stain -Impaired intestinal absorption of nutrients is called malabsorption. Significant malabsorption may present with diarrhea and steatorrhea (bulky, foul-smelling stools; visible oil droplets; greasy toilet ring), but more often patients have nonspecific symptoms such as weight loss, fatigue, or vague abdominal discomfort. Patients may also have characteristic findings due to specific nutrient deficiencies. Generalized malabsorption is commonly due to defects in pancreatic secretion (eg, chronic pancreatitis, cystic fibrosis), mucosal disorders (eg, celiac disease, inflammatory bowel disease), bacterial overgrowth (eg, gastrointestinal surgery, abnormal motility), or parasitic diseases (eg, Giardia). Dietary lipids are the macronutrient with the most complex digestive pathway. Fats are typically the earliest and most severely affected nutrient in generalized malabsorption, and testing for fat malabsorption is therefore the most sensitive strategy for screening for malabsorptive disorders. A qualitative assay of stool with Sudan III stain can quickly and easily identify unabsorbed fat and confirm malabsorption. (Stool should normally contain no measurable fat.)

A 52-year-old woman comes to the office due to fatigue for the last 2 weeks. The patient was previously healthy, but over the past 3 months, she has had significant weight loss without changing her diet. She also reports increased sweating, hand tremor, and decreased sleep. Examination shows diffuse, nontender enlargement of the thyroid gland. The eyeballs are protuberant. The remainder of the examination is notable for 1+ pitting edema in the ankles. Which of the following parameters is most likely to be decreased in this patient?

Systemic vascular resistance - This patient with an enlarged thyroid gland and multiple consistent symptoms (eg, fatigue, unintentional weight loss, sweating, tremor, insomnia) most likely has hyperthyroidism. Protuberance of the eyeballs (ie, exophthalmos) suggests Graves disease, specifically. In adults, the major effect of thyroid hormone is control of cellular metabolism, including the rate of oxygen consumption and use of proteins, carbohydrates, and lipids. As a result, hyperthyroidism causes characteristic cardiovascular effects: Increased metabolic demand in the peripheral tissues, combined with a direct effect of thyroid hormone on vascular smooth muscle, causes peripheral vasodilation, which leads to decreased systemic vascular resistance (SVR) and reduced diastolic blood pressure. Thyroid hormone has a direct sympathetic-like effect on the myocardium, which stimulates increased heart rate and contractility. A reflexive response to decreased SVR also contributes to these changes. With increased contractility, stroke volume is increased, resulting in increased pulse pressure and systolic blood pressure. Ejection fraction and cardiac output are also increased. Over time, some patients develop high-output heart failure due to the hyperdynamic circulatory state. Restoration of a euthyroid state normalizes cardiovascular hemodynamics and typically resolves any heart failure that has developed.