A 36-year-old woman with HIV comes to the office for evaluation of increased viral load.  The patient tested positive for HIV 4 years ago during a screening test performed after an episode of gonococcal urethritis.  Her initial CD4 cell count was 420/mm³ and viral load (plasma HIV RNA) was 150,000 copies/mL.  Since diagnosis, she has been taking antiretroviral therapy but occasionally forgets to take it.  A routine test performed a month ago revealed that her viral load had increased, and a repeat test showed similar results.  Genotypic resistance analysis reveals viral isolates that are resistant to nevirapine.  Which of the following agents in the patient’s treatment regimen most likely contributed to this finding?

A 20-year-old man comes to the office due to progressive dizziness, headaches, nausea, and difficulty walking for the past several months.  The headaches are worse with lifting heavy objects, coughing, and bending down.  The patient was recently diagnosed with hypertension and takes several antihypertensive agents.  Blood pressure is 170/96 mm Hg and pulse is 118/min.  Examination shows vertical nystagmus and left-sided limb ataxia.  MRI of the brain reveals a cystic mass.  The patient undergoes successful neurosurgery and is diagnosed with hemangioblastoma.  This patient is at highest risk of which of the following?

A 26-year-old man comes to the office due to an elevated hemoglobin level found during a blood donor screening test.  He has no symptoms or history of major illness and denies any family history of blood disorders.  He does not use tobacco, alcohol, or illicit drugs.  Physical examination is unremarkable.  Laboratory studies show a hematocrit of 58% and an erythrocyte count of 6.22 million/mm³.  Further testing shows a markedly decreased level of 2,3-bisphosphoglycerate within red blood cells and decreased bisphosphoglycerate mutase enzyme activity.  The oxygen-binding properties of this patient’s hemoglobin most likely resemble which of the following?

A 22-year-old man comes to the office due to progressive involuntary movements of the arms for 2 years.  The movements are most pronounced when the arms are outstretched.  Vital signs are normal.  Examination shows dysarthria and a diffuse increase in muscle tone.  The liver is enlarged, and biopsy reveals an abnormally high tissue copper content.  A green-colored ring is apparent on eye examination.  The latter finding is most likely due to copper deposition in which of the following structures?

Researchers investigating the bactericidal activity of neutrophils culture Staphylococcus aureus in an enriched liquid media.  After several hours, high concentrations of N-formylmethionine, a potent chemotactic agent, can be detected in the mixture.  Next, a drop of the culture is placed on a slide containing mature neutrophils, and the slide is placed under the light microscope.  The neutrophils are seen migrating toward the bacteria and engulf them on contact.  The bacteria subsequently undergo rapid lysis within the neutrophils.  Which of the following proteins is most likely to facilitate this bactericidal process?

A 4-year-old boy has recurrent episodes of severe hypoglycemia during fasting.  He has a family history of sudden death at a young age.  Comprehensive evaluation suggests decreased activity of the mitochondrial enzyme medium-chain acyl-CoA dehydrogenase (MCAD).  After isolating the enzyme from the patient’s leukocytes, analysis shows that the polypeptide chain contains the same number of amino acids as that of the wild-type enzyme.  However, further studies show minimal catalytic activity compared to the wild-type enzyme.  The gene coding for MCAD is known to have 12 exons and 11 introns.  Which of the following mutations is the most likely cause of this patient’s condition?

A 24-year-old woman, gravida 1 para 0, at 34 weeks gestation comes to the office for a routine prenatal visit.  Since her last visit, she has noticed a new breast lump.  Her pregnancy has been uncomplicated other than a minor motor vehicle collision as a passenger earlier in the pregnancy.  The patient takes a daily prenatal vitamin.  On breast examination, a 3-cm, nontender, firm, mobile mass is palpated in the lower outer quadrant of the left breast.  Shortly after delivery, the mass decreases in size but remains nontender, firm, and mobile.  Which of the following is the most likely diagnosis?

A 33-year-old man comes to the clinic due to multiple scattered skin lesions.  He has a strong family history of skin tumors.  Biopsy of a skin lesion demonstrates aggregates of large cells at the dermoepidermal junction that fuse with adjacent nests.  The individual atypical cells have irregular nuclear contours, are hyperchromatic, and are round or spindle shaped.  A CDKN2A mutation is identified in the atypical cells.  This patient is most likely predisposed to developing which of the following tumors?

A 65-year-old man is brought to the emergency department with severe chest pain.  He reports that the pain began suddenly in the middle of the night.  Medical history is significant for a recent upper respiratory infection, coronary artery disease, chronic obstructive pulmonary disease, hypertension, type 2 diabetes mellitus, obstructive sleep apnea, and chronic kidney disease.  He has a history of poor adherence to medications.  He smokes a pack of cigarettes and drinks 1 or 2 bottles of beer daily.  Blood pressure is 180/120 mm Hg and pulse is 90/min.  ECG reveals no acute ST segment or T wave changes.  Chest x-ray is shown in the exhibit.  Which of the following is the most likely diagnosis?

A researcher is testing the effect of Drug X on ligand-mediated ion flow in neurons.  The results of his experiments are shown on the graph below.

Which of the following drugs has an action most similar to that of Drug X?

A 54-year-old male undergoes invasive cardiovascular testing in response to exercise.  The following effects are observed:

Which of the following best describes the observed changes?

A 61-year-old man comes to the clinic due to several months of difficulty walking and frequent falls.  The patient has trouble controlling his leg movements and feels “wobbly” on his feet.  He has a history of chronic alcohol abuse and continues to drink 1 pint of vodka daily despite repeated hospitalizations for alcohol-induced pancreatitis.  On physical examination, his gait is broad-based and unsteady.  He is unable to walk in a straight line while touching the heel of one foot to the toe of the other with each step.  Finger-to-nose testing is grossly normal, but he is unable to perform heel-to-shin testing.  Cognitive evaluation is normal.  This patient’s symptoms are most likely the result of damage to a derivative of which of the following structures?

A pharmacological researcher is studying the structure of several pancreatic beta cell proteins to develop a new drug.  During an experiment, human pancreatic cells are lysed and centrifuged.  A specific protein is isolated and purified from the supernatant.  Structural and biochemical analyses demonstrate that the protein is abundant in arginine and lysine residues.  It also contains a 30-amino-acid alpha-helical segment that consists of repeated leucine residues at every seventh position.  The protein analyzed in this experiment most likely represents which of the following?

A 34-year-old man comes to the office due to fevers and fatigue for the last month.  He has lost 4.5 kg (10 lb) over the last 2 weeks and also reports some “lumps” in his neck.  Over the past few weeks, he has often awakened at night “drenched in sweat” to the point that he has to change shirts.  The patient is a missionary who recently returned from a 3-month mission to South Asia, where he stayed mostly in rural settings.  He did not visit a travel clinic prior to his trip.  His wife was treated for malaria in South Asia; otherwise, he has had no sick contacts.  The patient has no known medical problems and takes no medications.  Physical examination is notable for cervical lymphadenopathy.  The oral pharynx is otherwise unremarkable.  HIV testing is negative.  Lymph node biopsy findings are shown in the image below.

Which of the following is the most likely diagnosis?

A pharmaceutical researcher is in the process of developing a novel drug that blocks angiotensin II-mediated aldosterone release.  During the study, she finds that angiotensin II binds to a transmembrane G protein-coupled receptor in the zona glomerulosa of the adrenal gland.  After the ligand binds, the receptor undergoes conformational changes leading to activation of the G protein.  The enzyme activated by the G protein hydrolyzes membrane-bound phospholipids.  Which of the following events is the most likely next step in intracellular signaling?

A pharmaceutical researcher is trying to develop a novel chemotherapeutic drug that inhibits DNA synthesis.  During the study, cancer cell lines are exposed to isotopically labeled carbon dioxide and incubated in enriched growth media.  Nuclear magnetic resonance spectroscopy reveals that the carbon isotopes become incorporated into the nucleobases of newly synthesized nuclear DNA.  The first reaction in this process occurs in which of the following cellular structures?

A 32-year-old female presents to the emergency department with lower abdominal pain and nausea.  She describes the pain as dull and reports that it is exacerbated by movement.  She also complains of urinary frequency.  While lying supine, the patient is asked to flex her right hip against resistance.  This maneuver causes extreme pain.  Inflammation of which of the following structures is most likely responsible for this physical examination finding?

A 34-year-old man who drinks alcohol excessively comes to the emergency department due to progressive exertional dyspnea.  He also describes swelling of his ankles and sometimes he wakes up during the night with severe shortness of breath.  He has had no chest pain but reports intermittent palpitations.  He receives symptomatic treatment; however, he leaves the hospital against medical advice and has no further follow-up.  Several months later the patient dies suddenly in his apartment.  Autopsy shows enlarged cardiac ventricles with mild myocardial hypertrophy and interstitial fibrosis.  Which of the following is the most likely diagnosis?

A 32-year-old man with HIV infection comes to the emergency department after several days of lethargy, fever, and frontal headache.  India ink staining of his cerebrospinal fluid shows encapsulated yeast.  The patient is hospitalized and the appropriate treatment is started.  Several days later, he develops impaired renal function and hypokalemia.  The antimicrobial agent most likely responsible for these side effects acts at which of the following fungal cell structures?

A 46-year-old man comes to the office due to fatigability, weight gain, and lower extremity edema that developed over the last 1-2 weeks.  On examination, blood pressure is 200/120 mm Hg and pulse is 90/min.  Vesicular breath sounds are heard on chest auscultation.  There is 1+ pitting edema of the bilateral lower extremities.  Laboratory studies are significant for a serum creatinine level of 3.1 mg/dL and urinalysis findings of 3+ blood and 2+ protein.  A kidney biopsy is performed.  Immunofluorescent staining of the renal biopsy specimen for IgG is shown in the image below:

Which of the following is the most likely cause of this patient’s symptoms?

A 24-year-old woman, gravida 3, para 2, comes to the office due to irregular bleeding over the past 2 months.  She is unsure of the date of her last menstrual period, and a urine pregnancy test is positive.  The patient had a dilation and curettage for a miscarriage last year.  On this visit, ultrasound of the pelvis reveals a central heterogeneous mass in the uterus with numerous discrete anechoic spaces.  The patient undergoes a dilation and curettage, and pathology of the specimen reveals edematous chorionic villi.  Staining with p57 is negative.  The most likely cause of this patient’s condition is proliferation of which of the following?

A 32-year-old man is evaluated for recurrent renal calculi.  The patient was recently hospitalized due to renal colic and passed his 5th renal stone in the last 2 years.  He has no other medical conditions and takes no medications.  The patient eats a balanced diet and drinks plenty of fluids daily.  He has no family history of renal stones.  Analysis of the passed stone reveals that it is composed of calcium oxalate.  After further investigation, parathyroidectomy is planned.  During the surgery, the right superior gland is found to be enlarged, whereas the other 3 are small and atrophic.  Which of the following is the most likely cause of the gland shrinkage in this patient?

A 17-year-old girl comes to the office due to a persistent skin condition.  She reports having pimples on her face for the past few years, but the condition has recently worsened.  The patient feels disfigured and is embarrassed to leave her house.  She has tried several over-the-counter products without relief.  The patient has no other medical conditions; does not use tobacco, alcohol, or illicit drugs; and is not sexually active.  Physical examination findings are shown in the image below:

Topical tretinoin is prescribed.  This medication is most likely to improve this patient’s condition through which of the following mechanisms?

A 43-year-old man comes to the office for a regular checkup.  He reports no symptoms.  Medical history is significant for hypertension and diabetes mellitus type 2.  Current medications are enalapril and metformin.  The patient smokes a pack of cigarettes a day and consumes 1 or 2 cans of beer each evening.  He does not use illicit drugs.  His daily work mainly involves sitting at a computer desk.  The patient’s father was diagnosed with coronary artery disease at age 60.  Blood pressure is 150/95 mm Hg and pulse is 80/min.  BMI is 31 kg/m².  His most recent hemoglobin A1c was 7.2%.  Which of the following interventions would be the most beneficial for reducing this patient’s risk of myocardial infarction?

A 63-year-old man is evaluated for progressive dysphagia.  The patient has a prolonged history of gastroesophageal reflux disease.  Endoscopy shows an ulcerating mass in the distal esophagus, and biopsy confirms adenocarcinoma.  A minimally invasive esophageal resection is planned.  During the surgery, a laparoscope is introduced in the upper abdomen.  The esophagus is visualized entering the abdominal cavity through an opening in the diaphragm.  Dissection between the esophagus and the right crus of the diaphragm is started.  Which of the following structures is at greatest risk of injury during the dissection?

A 53-year-old man comes to the clinic due to intermittent, squeezing chest pain.  The patient reports that brisk walking and stair climbing elicit the pain.  He does not use tobacco or consume alcohol.  His mother has diabetes mellitus and his father died of a stroke at age 62.  Blood pressure is 150/95 mm Hg and heart rate is 80/min.  BMI is 32.5 kg/m².  On physical examination the heart rhythm is regular and there are no murmurs.  The lungs are clear to auscultation.  There is no peripheral edema.  Amlodipine monotherapy is initiated, and the patient reports improvement in his symptoms at his next office visit.  Which of the following points labeled below has most likely been affected by this patient’s treatment?

A 12-year-old boy is being evaluated for diabetes mellitus.  He has a strong family history of the disease; the patient’s older brother, father, and paternal grandfather were diagnosed with diabetes at a young age.  Despite developing diabetes early in life, however, these relatives have maintained very good glycemic control with dietary modification alone without the need for antidiabetic medications.  The patient’s BMI is normal.  An oral glucose tolerance test shows a fasting blood glucose of 107 mg/dL and a 2-hour postprandial glucose of 204 mg/dL.  This patient most likely has a deficiency involving which of the following enzymes?

A 4-month-old boy is brought to the office by his mother due to concerns regarding his development.  She says that he “doesn’t seem interested in feeding and isn’t as interactive as my other children were at his age.”  Physical examination shows hepatomegaly and poor muscle tone in the face and extremities.  A systolic murmur is heard over the cardiac apex, and echocardiogram shows an enlarged heart.  Skeletal muscle biopsy reveals abundant intracellular membrane-bound material that is periodic acid-Schiff-positive.  This patient most likely has deficiency of an enzyme that normally functions in which of the following cellular compartments?

A 5-month-old boy is brought to the emergency department after a tonic-clonic seizure.  The mother noticed he began convulsing when she was getting ready to feed him this morning.  The parents state that he seems normal otherwise, except for having a “big belly.”  The patient was born at full-term without any pregnancy-related complications and has been exclusively breastfed.  Weight, length, and head circumference are <5th percentile.  Physical examination shows hepatomegaly.  Laboratory studies reveal a blood glucose level of 34 mg/dL.  Administration of fructose syrup results in lactic acidosis without increasing the blood glucose level.  Which of the following enzymes is most likely deficient in this patient?

A 21-year-old man comes to the office to evaluate impotence.  He reports low libido, with difficulty achieving and sustaining an erection.  The patient also has no nocturnal erections.  He has no pain with intercourse, dysuria, urethral discharge, or genital lesions.  The patient saw his pediatrician at age 16 due to his perceived lack of secondary sexual development but was told that he had delayed puberty, and no further investigations were performed.  Physical examination shows sparse body hair, gynecomastia, and small, firm testes.  Laboratory analyses show elevated LH, low testosterone, and normal prolactin levels.  Which of the following investigations is most likely to yield a diagnosis?

A 78-year-old resident of an extended care facility is brought to the emergency department due to lethargy, fevers, and poor oral intake for the last day.  Temperature is 39 C (102 F), blood pressure is 70/40 mm Hg, and pulse is 120/min and regular.  On examination, the patient is lethargic but arousable.  His extremities are warm.  A Foley catheter is inserted into the bladder and drains 500 mL of cloudy urine.  Five hours after admission, the patient begins to bleed from the nose and venipuncture sites, and the Foley catheter begins to drain blood-tinged urine.  Which of the following sets of laboratory abnormalities is most likely to be seen in this patient?

A 46-year-old man comes to the office due to a 3-day history of low back pain.  The patient was in his usual state of health when he suddenly developed moderately severe back pain while building a storage shed in his backyard.  The pain shoots down the back of his leg into the foot and worsens when ambulating; ibuprofen provides some relief.  He also has partial numbness in the left leg but no urinary or bowel symptoms.  The patient has smoked half a pack of cigarettes daily for 20 years and occasionally drinks alcohol.  Vital signs are normal and his BMI is 31 kg/m².  With the patient supine on the table, raising the left leg beyond 45° reproduces his pain.  The ankle reflex is diminished on the left side compared to the right.  MRI of the lumbosacral spine shows S1 nerve root impingement.  Which of the following pathologic process is the most likely cause of this patient’s nerve compression?

An 8-year-old boy with sickle cell disease is brought to the emergency department with 2 days of high-grade fevers, poor appetite, and persistent right knee pain.  The pain worsened today and he now refuses to bear weight.  The patient’s temperature is 39.5 C (103.1 F).  Physical examination reveals localized warmth, swelling, and tenderness just superior to the right knee.  An MRI of the right lower extremity confirms the diagnosis, and the child undergoes surgical debridement.  Which of the following is characteristic of the most likely causative organism?

A 67-year-old man is brought to the emergency department due to unresponsiveness.  He developed sudden-onset weakness in the extremities and face following a heated argument with his son and within minutes became unresponsive.  The patient has a history of hypertension and has not been taking his medications regularly.  Blood pressure is 188/104 mm Hg and pulse is 62/min and regular.  Physical examination shows a comatose patient with pinpoint pupils and rigid, extended upper and lower extremities.  Despite appropriate management, the patient dies 2 hours later.  Autopsy is most likely to show intracranial hemorrhage in which of the following areas?

A 43-year-old man comes to the office due to progressively worsening headaches over the past 3 months.  The headaches occur almost daily and are particularly worse at nighttime.  The patient characterizes the headaches as dull and moderately severe and notes that they are often associated with nausea and vomiting.  Lately, he has also been experiencing visual disturbances.  The patient has not had any recent head trauma or loss of consciousness.  His temperature is 37.2 C (99 F), blood pressure is 170/96 mm Hg, pulse is 60/min, and respirations are 8/min.  Ophthalmologic examination shows bilateral papilledema.  MRI of the brain is shown in the image below.

Which of the following pathophysiologic mechanisms is most likely underlying this patient’s headaches?

A 34-year-old man comes to the office with a rash on his palms.  He recently developed knee pain that he attributes to standing frequently at work.  He has been managing the pain with acetaminophen.  The patient also had “pink eye” for which he used topical antibiotic eye drops that he found at his parents’ apartment.  He has not had any fevers.  The patient lives alone and does not recall any sick contacts.  He has not traveled outside the city recently.  He has no other medical problems and does not take any medications on a regular basis.  He has no known drug allergies.  His sister has had bouts of uveitis.  Examination shows plaques and pustules on his palms.  Which of the following is the most likely initiating event for this patient’s constellation of conditions?

A 34-year-old nulligravid woman comes to the office for a colposcopy due to a recent abnormal Pap test.  She has traveled extensively for work over the past 7 years and has not had access to routine health care.  The patient smokes tobacco occasionally and drinks 2 or 3 glasses of wine weekly but does not use recreational drugs.  She has no chronic medical conditions and takes no medications; immunizations are up to date.  During the colposcopy, a biopsy sample is collected.  Which of the following normal cell types will most likely be found on histologic evaluation of this patient’s biopsy sample?

A 32-year-old construction worker comes to the emergency department due to a day of jaw pain and difficulty chewing.  The patient has no significant medical history but has not seen a physician in over ten years.  On physical examination, he has difficulty fully opening the mouth.  There is no tenderness of the temporomandibular joint or oropharyngeal mucosal lesions.  Touching the posterior pharyngeal wall with a tongue depressor elicits strong spasm of the masseter muscles.  Which of the following is the most likely cause of this patient’s current condition?

A 24-year-old man comes to the office due to several days of poor appetite, abdominal discomfort, and dark urine.  The patient worked as an emergency medical technician for 2 years and applied to graduate school last year.  He spent the past several weeks traveling in India before beginning the semester.  Temperature is 37.4 C (99.3 F).  Physical examination is significant for yellow discoloration of the sclerae and skin.  Laboratory analysis reveals the following:

Which of the following is the most likely cause of these findings?