A 67-year-old man comes to the emergency department due to progressive weakness and numbness in his feet over the past month.  The patient has had difficulty maintaining balance when walking and reports generally feeling weak.  He has a history of alcohol use disorder and has been hospitalized for alcohol intoxication.  Neurologic examination shows decreased tactile and vibratory sensation in the feet and ankles bilaterally.  Gait is unsteady, and muscle strength is mildly decreased in both lower extremities.  Lower extremity deep tendon reflexes are hyperactive, and Babinski sign is present bilaterally.  Which of the following is the most likely cause of this patient’s current neurologic symptoms?

A 31-year-old man comes to the office due to difficulty chewing.  He is not able to enjoy chewing gum as he used to, and has also intermittently experienced double vision when reading or watching television for long periods.  The patient has no extremity weakness or sensory symptoms.  He has no other medical problems and takes no medications.  The patient does not use tobacco, alcohol, or illicit drugs.  Vital signs are normal.  Physical examination shows mild ptosis of the right eye.  The pupils are equal and reactive to light.  Muscle strength is 5/5 in all extremities.  Deep tendon reflexes are 2+ and symmetric.  Babinski sign is absent.  This patient’s condition is most likely associated with which of the following pathologic processes?

A 25-year-old man comes to the physician with persistent right knee pain.  X-ray of the knee shows a lytic lesion involving the distal femoral metaphysis, and biopsy confirms a diagnosis of osteosarcoma.  His past medical history is significant for enucleation of the right eye due to retinoblastoma.  Which of the following mechanisms is the most likely underlying cause of this patient’s condition?

A 64-year-old man comes to the hospital due to 2 days of progressive right knee pain.  The patient has a history of joint pain but reports that this episode is more severe and is associated with knee swelling.  He says, “I bumped my knee on a chair 5 days ago, and that must have started the problem.”  The patient has a history of hypertension, type 2 diabetes mellitus, and chronic hepatitis C.  He takes low-dose aspirin, metformin, lisinopril, and chlorthalidone.  He has not received hepatitis C treatment yet.  Arthrocentesis is performed and microscopic findings are shown in the image below.

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

A 14-month-old boy is brought to the office for evaluation of recurrent white patches on the inside of his cheeks.  The patches have been present for the past 2 days.  The parents state that the boy has a decreased appetite and has been refusing food.  They are concerned that he may have difficulty or pain with swallowing.  Vital signs are normal.  Examination shows a dysmorphic face and a cleft palate.  There are white patches on his tongue and buccal mucosa that have underlying erythema when the material is scraped off with a tongue depressor stick.  Microscopic examination of the white substance is shown in the image below:

Flow cytometry analysis of the patient’s blood shows a low CD3⁺ cell fraction but a normal CD20⁺ cell fraction.  This patient’s clinical findings are most likely due to which of the following underlying abnormalities?

A 22-year-old previously healthy man comes to the office due to paroxysmal occipital headaches for the past several months.  The headaches are characterized as dull and graded 6/10 in intensity.  The patient has also had episodic dizziness that is brought on by coughing or lifting heavy objects.  His symptoms are interfering with his job as a construction worker.  He has no history of head trauma, fever, nasal congestion, or hearing loss.  Physical examination is unremarkable.  MRI of the head is shown below.

Which of the following is the most likely diagnosis?

A 16-year-old girl comes to the office due to primary amenorrhea.  She has never menstruated, but her sister and mother had menarche at age 14.  The patient has been healthy and takes no medications.  She plays varsity soccer in the fall and runs track in the spring.  Examination shows Tanner stage 5 breasts and a vagina that ends in a blind pouch.  A bulge is palpated in the left groin.  Serum testosterone level is 900 ng/dL (normal: 15-75 for female patients, 300-1000 for male patients).  Which of the following is the most likely cause of this patient’s condition?

A 52-year-old woman comes to the office due to a 6-month history of episodic headaches associated with fast heartbeat, nausea, and diaphoresis.  Between episodes, the patient has had mild anxiety and fatigue but otherwise has felt well.  She recently underwent a screening colonoscopy, during which she had another symptomatic episode.  Blood pressure is 138/82 mm Hg and pulse is 85/min.  CT scan of the abdomen reveals a right adrenal mass; the patient is scheduled for surgery to remove it.  Which of the following medications should be initiated first in preparation for this patient’s surgery?

A 2-day-old boy was born at 25 weeks gestation by vaginal delivery to a 38-year-old woman who presented with preterm premature rupture of membranes.  Apgar scores were 3 and 5 at 1 and 5 minutes, respectively.  The infant was intubated in the delivery room and quickly transported to the neonatal intensive care unit for mechanical ventilation and ongoing management of severe respiratory distress due to surfactant deficiency.  He develops a bulging fontanelle, intermittent apnea, and decerebrate posturing and dies.  Autopsy reveals bilateral thrombi in the lateral ventricles.  Which of the following is the most likely underlying cause of this patient’s condition?

A 64-year-old male is treated with combined chemotherapy for a mediastinal mass.  Two months later, he develops high-frequency hearing loss.  Which of the following drugs is most likely responsible for his change in condition?

A 68-year-old man comes to the office after 6 weeks of progressive dyspnea, nonproductive cough, and malaise.  He has difficulty climbing a flight of stairs due to shortness of breath.  The patient has a history of rheumatoid arthritis, hypothyroidism, gastroesophageal reflux disease, erectile dysfunction, and difficult-to-control atrial fibrillation with rapid ventricular response.  Temperature is 38.1 C (100.6 F), blood pressure is 130/70 mm Hg, pulse is 88/min, and respirations are 20/min.  Physical examination shows bilateral inspiratory crackles and slight ulnar deviation of both wrists, but no arthralgias or rashes.  There is no peripheral edema and jugular venous pressure is normal.  Chest x-ray reveals patchy areas of interstitial infiltration throughout the lungs.  White blood cell count is normal.  Which of the following medications is most likely responsible for this patient’s current symptoms?

A 54-year-old woman comes to the office for follow-up of right hip pain.  X-rays of the hip reveal moderate degenerative joint disease.  Lately, the pain has gotten worse, requiring daily medication use.  The patient has also experienced occasional epigastric pain and has chronic idiopathic constipation, but otherwise feels well.  Medical history is significant for recurrent Clostridioides difficile colitis following a course of antibiotics 3 years ago.  She does not use tobacco, alcohol, or illicit drugs.  Vital signs are normal.  BMI is 34 kg/m².  The patient is counseled on activity and weight loss and is prescribed misoprostol in addition to her current medications.  Which of the following pathways in the parietal cell is most likely to be directly affected by this additional medication?

A 35-year-old man comes to the emergency department due to worsening shortness of breath for several days.  The patient has no prior medical conditions but has chronic nasal congestion that has persisted despite use of over-the-counter decongestants.  He has also been taking ibuprofen since injuring his lower back while moving heavy furniture a week ago.  The patient occasionally smokes marijuana but does not use tobacco or alcohol.  Temperature is 36.7 C (98 F), blood pressure is 120/70 mm Hg, pulse is 82/min, and respirations are 20/min.  Physical examination shows fleshy polyps in the nares.  When asked to take a deep breath, the patient coughs with forced expiration.  Bilateral expiratory wheezes are present.  The patient’s current symptoms are most likely related to an increase in which of the following substances?

A 65-year-old man comes to the clinic due to a painless, slowly enlarging neck mass.  Physical examination shows firm, nontender right submandibular lymphadenopathy.  Biopsy of an involved lymph node reveals sheets of malignant cells that have prominent intercellular bridging and several foci of central keratinization within concentric layers of squamous cells.  Which of the following is the most likely primary site of origin of this patient’s cancer?

A 30-year-old man comes to the office with his wife for prenatal counseling.  At the age of 14, the patient was found to have a heart murmur on routine physical examination, and an echocardiogram performed at that time showed mild aortic root dilation.  At age 18, he developed lens subluxation, and his current medical problems include scoliosis and recurrent patellar dislocations.  Genetic testing reveals an FBN1 gene mutation that causes production of a truncated fibrillin protein.  Similar gene mutations are identified in several other family members, as detailed in the pedigree shown.  Physical examination findings are given in the corresponding table.  Which of the following is the most likely explanation for the findings in this family?

A 56-year-old man has occasional squeezing retrosternal chest pain that lasts 5-10 minutes.  Symptoms initially occurred only during exertion but lately have been happening at rest as well.  The patient has no shortness of breath or dizziness.  Medical history includes hypertension, type 2 diabetes mellitus, and hyperlipidemia.  BMI is 30 kg/m².  Sublingual nitroglycerin is prescribed.  During an episode of chest pain, the patient takes 3 consecutive sublingual nitroglycerin tablets and his pain subsides.  Which of the following sets of hemodynamic changes most likely occurred in this patient after intake of the medication?

A 2-year-old girl is evaluated in the office for frequent, foul-smelling diarrhea and oily stools that float.  Review of her growth chart indicates poor weight gain.  Examination shows a thin, short toddler with bilateral wheezing and crackles on lung auscultation.  An inherited defect involving the cystic fibrosis transmembrane conductance regulator (CFTR) protein is suspected.  Sodium and chloride body fluid levels (relative to normal) are as follows:

Which of the following best explains the difference in electrolyte findings between the 2 types of body fluids?

A 5-year-old boy is brought to the clinic due to recurrent muscle spasms in his hands.  The patient’s parents report that his height has not increased for the last 1-2 years.  He takes no medications or over-the-counter supplements.  On physical examination, the patient has short stature, short fingers, and a round face.  Laboratory studies reveal a low serum calcium level and elevated serum phosphorus and parathyroid hormone concentrations.  Serum creatinine is normal.  Which of the following abnormalities is the most likely cause of this patient’s condition?

A researcher is attempting to locate the position of the β-globin gene on chromosome 11 using the RNA hybridization technique.  Chromosomal DNA is first exposed to restriction endonucleases, creating numerous DNA fragments that are then fractionated using gel electrophoresis.  Each DNA fragment is subsequently hybridized with purified mature β-globin mRNA.  Under the appropriate conditions, DNA partially denatures, allowing mRNA to displace the homologous DNA strand and form a DNA-mRNA hybrid.  Electron microscopy of these DNA-mRNA hybrids reveals several DNA loops, as shown in the image below.

Which of the following is the most likely explanation for the formation of these DNA loops?

A genetic study is performed on several patients diagnosed with β-thalassemia in a university hospital.  The patients’ beta globin genes, which contain 3 exons and untranslated regions at both ends, are sequenced and evaluated.  Of the studied patients, some were found to have missense mutation in exon 1, a few with nonsense mutation in exon 3, and others with promoter site mutation.  However, all the patients have similar clinical manifestations of the disease.  Which of the following genetic principles best explains these findings?

A 15-year-old boy is brought to the office due to exercise intolerance.  The patient has had episodes of breathlessness, chest tightness, and wheezing after moderate exercise, especially in cold weather.  Symptoms usually resolve within an hour after the activity ends.  The patient has no prior medical conditions and takes no medications.  His brother has seasonal allergies.  Vital signs are within normal limits.  The lungs are clear to auscultation.  Spirometry reveals a normal FEV₁/FVC ratio.  Pharmacotherapy targeted against which of the following is most appropriate in management of this patient?

A 43-year-old man comes to the office due to progressive weakness and fatigue for the past year.  He also has had episodes of knee pain, dry mouth, and impotence and has developed a “strange tan” despite spending almost all of his time indoors.  Blood pressure is 120/70 mm Hg.  Physical examination shows mild hepatomegaly and atrophic testes.  The patient’s fasting blood glucose level is 252 mg/dL, and serum electrolytes are normal.  His urine is positive for glucose but negative for ketones and protein.  Which of the following is most likely to be seen in this patient?

A 45-year-old homeless man comes to the emergency department due to vague abdominal discomfort.  His symptoms began a week ago and are associated with anorexia and generalized weakness.  The patient was seen 6 months ago for similar symptoms.  He has a history of untreated chronic hepatitis C infection and alcohol abuse.  The patient is alert but appears disheveled.  Physical examination shows several spider angiomata, gynecomastia, and a distended abdomen.  Diffuse muscular wasting is noted.  Which of the following structures on the normal CT scan shown below is most likely to have increased pressure in this patient?

A new test is being developed to screen pregnant women for prior infection with parvovirus B19.  The test is designed as an enzyme-linked immunosorbent assay that uses parvovirus B19 antigen attached to plastic wells in the test kit.  The patient’s serum is added to one of the test wells, which is then washed out to remove nonspecifically bound protein.  The next step of the assay would most likely involve adding which of the following components to the well?

A 44-year-old man comes to the emergency department due to a rash on his left outer thigh.  The patient is an industrial worker and sustained an accidental iron burn to this area.  The burn site became significantly more inflamed, and a yellowish crust developed.  The patient has no past medical history and takes no medications.  Temperature is 37.1 C (98.8 C).  Physical examination shows plaques and thick crusts with golden hue on his left outer thigh, as seen in the image below.

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

An 8-year-old boy with cystic fibrosis is hospitalized due to fever, chills, and cough productive of greenish sputum.  He has been treated for bacterial pneumonia on several occasions.  Temperature is 38.8 C (101.8 F).  Physical examination reveals dullness to percussion and bronchial breath sounds over the right lung base.  Sputum cultures grow Pseudomonas aeruginosa, which is resistant to ciprofloxacin with a high minimum inhibitory concentration.  Repeat antibiotic sensitivity testing in a growth medium with a higher pH lowers the minimum inhibitory concentration of the drug.  Which of the following is the most likely mechanism of ciprofloxacin resistance in this bacterial isolate?

Physical examination of a girl shortly after birth shows a head circumference at the 90th percentile, mid-face hypoplasia, and humeral and femoral shortening.  The hands have shortened digits and a space between the third and fourth digits.  The patient was born to a 35-year-old woman who had an uncomplicated pregnancy.  However, the mother did not have prenatal care until 14 weeks gestation as she was unaware she was pregnant.  The girl’s parents have no significant medical history.  Which of the following is the most likely cause of this patient’s presentation?

A 9-month-old who has recurrent infections is found to have an abnormal gene coding for a cytoplasmic tyrosine kinase.  Normally, this tyrosine kinase is active in the bone marrow within CD19⁺ cells, leading to normal maturation and effective functioning.  The abnormal gene responsible for this patient’s condition can be mapped to which of the following?

A 26-year-old woman is evaluated for infertility.  Medical history is significant for acute lymphoblastic leukemia treated with chemotherapy and allogeneic stem cell transplantation 20 years ago.  Physical examination shows well-developed secondary sexual characteristics and normal female external genitalia.  Uterus is normal sized, and ovaries are nonpalpable.  Karyotyping from the peripheral blood sample shows the sex chromosomal findings shown below:

Which of the following best explains this patient’s karyotype findings?

A research scientist is studying the effects of an insulin gene mutation on the development of diabetes mellitus.  She finds that preproinsulin has a signal sequence at the N-terminal consisting of hydrophobic amino acids.  A guinea pig model is developed with several base pair deletions in the gene segment encoding this signal sequence.  Electron microscopy of the pancreatic beta cells from this guinea pig is most likely to show accumulation of hormonal precursors in which of the following cellular compartments?

A 7-day-old boy is brought to the emergency department for evaluation of vomiting.  He was born to a 32-year-old woman at term.  Over the past 2 days, the mother has noticed the infant is less interested in feeding, and today he has vomited a few times.  Temperature is 37 C (98.6 F), pulse is 190/min, and respirations are 42/min.  The infant is lethargic on examination.  No murmurs are noted, and breath sounds are equal bilaterally.  The abdomen is soft, and there is no hepatomegaly.  Pulses are weak, and capillary refill is delayed.  Laboratory results are as follows:

The enzyme that is most likely deficient in this patient requires which of the following cofactors for proper functioning?

A 34-year-old man comes to the clinic to evaluate infertility.  He and his wife have been trying to conceive for 2 years.  His wife completed a full anatomic and hormonal evaluation with normal results.  The patient had normal puberty and reports normal libido and erectile function.  He takes no medications.  Physical examination shows normal secondary sexual characteristics and bilaterally descended testes that are slightly smaller than normal.  Serum concentrations of testosterone and LH are normal.  Testicular biopsy reveals that the testosterone concentration in his seminiferous tubules and epididymis is abnormally low.  Dysfunction of which of the following cells is the most likely cause of this patient’s findings?

A clinical researcher is studying the metabolic effects of a new hormone analogue.  In an experiment, serum glucose levels and activity of several hepatic enzymes are measured before and after the hormone analogue is administered to an animal.  It is determined that this agent leads to increased activity of phosphorylase kinase and phosphoenolpyruvate carboxykinase in the liver, resulting in rapid elevation of blood glucose levels.  This new agent most likely acts through which of the following proteins in hepatocytes?

A 16-year-old girl is evaluated for heat intolerance and excessive sweating.  She has had excessive sweating in her axillae, even with mild heat or emotional stimuli, leading to skin maceration.  The patient feels embarrassed as the condition has caused staining of her clothes on many occasions.  She has used antiperspirants and anticholinergic medications, but they have not provided much relief.  Past medical history is negative for other neurologic conditions, thyroid disorders, and cardiac conduction system disease.  Physical examination is unremarkable.  Extensive laboratory testing, including thyroid function tests, has not identified a correctable cause for her sweating.  Surgical interruption of which of the following structures is most likely to help this patient’s condition?

A 65-year-old man comes to the office due to worsening right knee pain.  He also reports brief episodes of “locking” in the knee during which he is unable to move the joint for several minutes.  His other medical problems include hypertension, type 2 diabetes mellitus, and chronic kidney disease.  The patient has smoked a pack of cigarettes daily for 30 years and drinks 1 or 2 glasses of wine every evening.  Temperature is 37 C (98.6 F), blood pressure is 130/70 mm Hg, and pulse is 68/min.  BMI is 32 kg/m².  Right knee examination shows joint swelling and limited range of motion.  Arthroscopic evaluation reveals free-floating tissue fragments in the joint space, a microscopic image of which is shown below.

Which of the following is an important step in the pathogenesis of this patient’s current condition?

A 40-year-old woman comes to the office for counseling regarding her risk of developing cancer.  Her mother died of ovarian cancer at age 54, and her sister was recently diagnosed with endometrial cancer at age 43.  Genetic testing shows that the patient has Lynch syndrome, significantly increasing her likelihood of developing endometrial and ovarian cancer.  She undergoes prophylactic hysterectomy and bilateral salpingo-oophorectomy.  Normal female pelvic viscera are shown in the image below.  Which of the following structures is most likely to be found in the inguinal canal?

A 32-year-old woman comes to the emergency department due to an acute headache, palpitations, flushing, and blurred vision for the past 30 minutes.  She has had several similar episodes over the last 6 weeks, and the symptoms spontaneously resolve after 30-60 minutes.  The patient has no significant medical history and takes no medications.  She does not use tobacco, alcohol, or illicit drugs.  Blood pressure is 210/112 mm Hg and pulse is 115/min and regular.  On physical examination, the patient is diaphoretic.  Chest and abdominal examinations show no abnormalities.  Imaging studies reveal a 4-cm para-aortic mass at the level of the aortic bifurcation.  Which of the following is most likely to be elevated in this patient?

A 46-year-old man comes to the emergency department due to sudden-onset, right-sided, sharp chest pain and shortness of breath that began 2 hours ago.  The patient has no chronic medical problems and takes no medications.  He is a truck driver and has smoked a pack of cigarettes daily for the last 25 years.  Blood pressure is 110/70 mm Hg and pulse is 98/min.  On physical examination, the patient appears anxious.  Chest auscultation reveals good air entry with bilateral vesicular breath sounds and no wheezing or crackles.  The right leg is swollen and tender to palpation.  Which of the following sets of arterial blood gas findings is most likely present in this patient?