A 56-year-old woman with type 2 diabetes mellitus is being treated with pioglitazone to improve her sensitivity to insulin and with gemfibrozil to decrease her serum triglyceride concentration. These drugs both initiate their therapeutic effects by binding to which of the following receptor groups?

A 4-day-old male newborn who was born at home is brought to the emergency department because of respiratory distress and cyanosis. The mother reports that she found him in his crib not breathing. He began to breathe again after she picked him up. Examination shows a narrow thorax. His ears have periauricular skin tags. He also has micrognathia, glossoptosis, a mandibular cleft, and a short palate. Tracheostomy relieves his respiratory distress. Defects such as these are consistent with altered development of which of the following pharyngeal arches?

A group of men between the ages of 25 and 30 years and a group of men between the ages of 75 and 80 years were deprived of water for 24 hours. Renal function measurements for both groups are shown:

Which of the following changes associated with aging is the most likely cause of the difference in urine concentrating ability between the two groups?

An investigator is studying a new hormone, Hormone X. To determine its cell target, a purified, radioactively labeled form of Hormone X is added to tissue cultures. Subsequent analysis shows that the radioactivity is detected only around the region of the plasma membrane. Hormone X is most similar to which of the following hormones?

A 66-year-old right-handed man has a thrombotic stroke. A CT scan of the head is shown. Which of the following is the most likely neurologic finding in this patient?

A 19-year-old woman comes to the physician because of a 3-day history of fever, shortness of breath, cough productive of blood-tinged sputum, rash on her legs, and pain of her groin. She lives on a small farm in rural New Mexico and says that all three of her cats have been infested with fleas. She is in respiratory distress. Her temperature is 39°C (102.2°F), pulse is 104/min, respirations are 28/min, and blood pressure is 100/60 mm Hg. Physical examination shows a 1-cm ulcer on the right lower extremity and numerous erythematous macular lesions over both lower extremities. There is a fluctuant 3 x 5-cm mass in the femoral lymph node chain. A chest x-ray shows bilateral infiltrates. A Gram stain of purulent material aspirated from the femoral mass shows numerous neutrophils and few gram-negative bacilli. Which of the following is the most likely causal organism?

A 55-year-old woman comes to the physician because of a 6-month history of progressive shortness of breath while climbing stairs and constant fatigue. She is 163 cm (5 ft 4 in) tall and weighs 107 kg (235 lb); BMI is 40 kg/m2. Her blood pressure is 170/110 mm Hg on three separate readings. Physical examination shows no other abnormalities. Echocardiography shows an ejection fraction of 45%. There are no regional wall motion or valvular abnormalities. An ECG shows that the sum of the magnitudes of the S wave in lead V2 and the R wave in lead V5 is 45 mm (scale=10 mm/mV). Which of the following cellular changes is most likely in this patient’s left ventricle compared with normal?

A healthy 25-year-old man participates in a study of muscle function. The electrophysiologic observations made on a muscle biopsy specimen are shown. Via iontophoresis, 1 pM acetylcholine (ACh) was applied to the muscle surface. Extracellular Ca2+concentration was decreased to prevent end-plate potentials from acting as a suprathreshold for muscle action potentials.

Based on these findings, which of the following electrophysiologic characteristics is expected in a muscle biopsy specimen from a patient with acute botulism?

A 9-year-old girl is brought to the clinic by her mother because of areas of hair loss on her scalp that the mother first noticed 1 week ago. The patient otherwise has been well. There is no personal or family history of serious illness. She receives no medications. The patient transferred from her neighborhood elementary school to a private school for gifted children 3 months ago. The mother says that no one in the house has used new shampoos, soaps, or detergents recently. The patient’s growth and development have been normal. The child appears healthy. Vital signs are within normal limits. Examination of the scalp shows two irregularly shaped, quarter-sized areas of alopecia on the right side of the head. Short, broken hairs are noted within these areas, but there is no scaling or erythema. Which of the following is the most likely diagnosis?

During an experiment, investigators use an in vitro cell culture system to study leukocyte function. As part of the study, a new drug that prevents polymerization of actin filaments is tested. Which of the following leukocyte functions is most likely to be inhibited by this new drug?

A 24-year-old man with AIDS comes to the physician because of a 1-month history of abdominal cramps and watery diarrhea. These symptoms have become increasingly severe during the past 5 days. His pulse is 95/min. Physical examination shows dry mucous membranes and decreased skin turgor. A biopsy specimen of the colon is shown in the photomicrograph. Which of the following is the most likely causal organism?

A 51-year-old woman comes to the physician because of a 6-month history of burning abdominal pain that occurs 1 to 2 hours after eating. She sweats profusely and has light¬headedness when she stands. Her blood pressure is 105/70 mm Hg while standing. Physical examination shows epigastric tenderness. ACT scan of the abdomen shows a 2¬cm mass on the proximal duodenum. Gastrin released by the tumor cells stimulates which of the following labeled cells in the photomicrograph shown to release hydrogen ions?

A 30-year-old man is brought to the physician by his wife because of a 1 -day history of irrational behavior and severe abdominal pain. He began treatment with trimethoprim- sulfamethoxazole for a urinary tract infection 3 days ago. His urine turned a light burgundy color during a similar episode 1 year ago. His mother and his maternal grandfather have had similar symptoms. He appears anxious and restless. His pulse is 96/min. Physical examination shows diaphoresis. Serum studies show increased concentrations of 5-aminolevulinic acid (5-ALA) and porphobilinogen. The physician suspects that a mutant allele is causing decreased activity of an enzyme involved in heme biosynthesis. This enzyme is most likely which of the following?

A 28-year-old man comes to the physician for a routine health maintenance examination. He is from Jamaica. He has practiced Rastafarianism all his life and follows a diet consisting only of natural juices, fruits, and grains. He also regularly smokes marijuana as part of his religion. Physical examination shows no abnormalities. His hematocrit is 32%, and serum vitamin E312 (cobalamin) concentration is within the reference range. Which of the following best describes the erythrocytes in this patient?

A 3-year-old girl is brought to the emergency department by her mother 1 hour after she was found with a half-empty bottle of her grandmother’s diabetes medication. The mother tells the physician that the child consumed approximately 25 metformin tablets. Physical examination shows no abnormalities. This patient is at greatest risk for which of the following serum abnormalities?

A 40-year-old man comes to the physician for a routine examination. He has smoked 2 packs of cigarettes daily for 20 years. Which of the following initial statements by the physician is likely to be most effective in encouraging this patient to stop smoking?

A 55-year-old man with long-standing type 2 diabetes mellitus comes to the physician because of a 2-day history of fever, chills, nausea, and swelling of his left leg. His temperature is 38.9°C (102°F), and pulse is 110/min. Examination of the left lower extremity shows a warm, tender, erythematous, blanching rash. A photograph of the left lower extremity is shown. A photomicrograph of a Gram stain of a blood culture is shown. Which of the following is the most likely causal organism?

A 55-year-old man is found to have gastroesophageal reflux disease. In addition to recommending lifestyle changes, the physician prescribes an agent that binds irreversibly to its site of action to inhibit gastric acid formation. Which of the following agents was most likely prescribed?

A study is conducted to measure survival following a diagnosis of lung, colon, or bladder cancer. Data from a statewide cancer registry are used. The graph shows survival plotted against the number of years after diagnosis for each cancer. Which of the following is the most accurate interpretation of these data concerning mortality?

A 48-year-old woman comes to the physician because of increasingly severe right flank pain during the past 3 weeks. Pelvic examination shows a normal-appearing vagina and cervix. A mass is palpated in the right pelvis during bimanual examination. Ultrasonography of the abdomen shows a mass associated with the right ovary. An MRI of the abdomen is suggestive of ovarian cancer. Which of the following is the location of the lymph nodes to which the ovaries first drain?

A 1-year-old girl is brought to the physician by her parents because of developmental delay. Physical examination shows a coarse facial appearance, clouded corneas in both eyes, hepatosplenomegaly, stiff joints, and developmental delay. Urine studies show an increased concentration of dermatan sulfate and heparan sulfate. Which of the following enzymes is most likely impaired in this patient?

A 60-year-old woman comes to the physician because of vaginal bleeding for 6 weeks. Menarche occurred at the age of 12 years, and menses had occurred at regular 30-day intervals. She had three term pregnancies by the age of 25 years. She has been receiving conjugated equine estrogen therapy since menopause 10 years ago. She has smoked 1 pack of cigarettes daily for 40 years. She drinks alcoholic beverages five times weekly. Physical examination and laboratory studies show no abnormalities. An endometrial biopsy specimen shows endometrial adenocarcinoma. Which of the following is the strongest predisposing risk factor for the biopsy findings?

A study is conducted to assess the effects of aging on cognitive and physiologic function. Participants are recruited via advertisements in the local and regional news media, and all persons who answer the advertisement are selected for study. Which of the following best describes this sampling technique?

A 31 -year-old man who works as a chef comes to the emergency department 30 minutes after accidentally cutting his right thumb with a knife. Examination of the right hand shows a 3-cm-long, 0.6-cm-deep laceration of the thumb. The wound is cleaned, sutured, and heals normally, leaving a faint scar by 1 year after the injury. The remodeling of the scar that occurred during the first year after injury is primarily mediated by which of the following?

A 60-year-old man comes to the physician because of a 1-month history of progressive shortness of breath with exertion. Examination of the chest shows:

Which of the following is the most likely diagnosis?

A 34-year-old man who is seropositive for HIV has a neoplasm manifested as violaceous raised cutaneous plaques (erythematous cutaneous plaques). Examination of tissue obtained on biopsy of the neoplasm is most likely to show which of the following?

A 56-year-old man with a history of alcohol dependence comes to the emergency department because of fever, night sweats, and a cough productive of bloody sputum. Laboratory studies of his sputum show numerous acid-fast rods arranged in small arrays. Which of the following components of the causal organism may be directly cytotoxic to macrophages?

A 51-year-old man has a cardiac output of 5 L/min and a right atrial pressure of 0 mm Hg at rest. The solid curve in the graph shows the relationship between right atrial pressure and cardiac output in a normal heart. Which of the following lettered points best represents the change in this relationship 5 seconds after a large arteriovenous fistula opens?

A 40-year-old woman at 5 months’ gestation comes to the physician for amniocentesis. Results show a normal 46,XY karyotype of the fetus. Four months later, the newborn is delivered and examination shows a female phenotype with mild clitoral enlargement. Ultrasonography shows the presence of male but not female genital ducts. This newborn most likely has a mutation of the gene of which of the following factors?

In the hypothetical distribution of laboratory values for a particular laboratory test in “normal” and “diseased” populations, respectively, which of the following lettered decision points will produce the maximum sensitivity for the detection of the disease?

An investigator is testing the hypothesis that advanced glycosylation end products (AGEs) lead to an increased synthesis of extracellular matrix by human renal mesangial cells. The cells are plated on two media: type I collagen treated extensively with glucose 6-phosphate to produce AGEs (first medium), and a control medium of untreated type I collagen. To confirm this hypothesis, mRNA that encodes for which of the following is most likely to be increased in cells incubated in the first medium compared with cells in the control medium?

A 26-year-old woman is brought to the emergency department by her husband after she ingested an overdose of narcotics. She is arousable only with deep painful stimuli. Her pulse is 110/min, respirations are 10/min, and blood pressure is 110/70 mm Hg. Cerebral blood flow is increased. Which of the following is the most likely cause of the increase in cerebral blood flow?

A 33-year-old African American woman comes to the physician because of dry eyes for 3 weeks. Physical examination shows decreased lacrimation and uveitis. There is mild hepatosplenomegaly. A chest x-ray shows prominent bilateral hilar adenopathy. Microscopic examination of a hilar lymph node is most likely to show which of the following pathologic conditions?

A 70-year-old woman with osteoporosis comes to the physician for her scheduled injection of ibandronate. She is accompanied by her 75-year-old husband. Physical examination shows no abnormalities. The husband asks the physician, “Why don’t I have osteoporosis? For the past 50 years we have done everything together, including eating the same foods and exercising. I even used to smoke and drink. Yet she has osteoporosis, and I don’t.” Which of the following is the most appropriate response?

A 48-year-old man with renal artery stenosis undergoes stent placement. Femoral access is used to place the stent. After entrance into the aorta, the guide wire should be advanced superiorly just beyond which of the following structures to approach the right renal artery in this patient?

A 16-year-old girl with cystic fibrosis is brought to the physician because of a 3-week history of generalized weakness, numbness and tingling of her arms and legs, and difficulty walking. She has not adhered to her medication regimen during the past 6 months. She appears alert and oriented. Her vital signs are within normal limits. Physical examination shows bilateral weakness and decreased deep tendon reflexes in the upper and lower extremities. She walks with an ataxic gait. The most likely cause of these findings is a deficiency of which of the following?

A 4-year-old boy is brought to the emergency department by his mother 6 hours after she noticed that his urine was red. He is otherwise feeling well. Fifteen days ago, the patient had a sore throat, fever, and cough. His mother thought he had the flu and treated him symptomatically with rest and analgesics, and his status improved until now. His temperature is 38.5°C (101.3°F), pulse is 110/min, respirations are 22/min, and blood pressure is 100/50 mm Hg. Physical examination shows normal breath and cardiac sounds, no organomegaly, and 1+ lower extremity edema, bilaterally. Laboratory studies show:

Which of the following is the most likely diagnosis?

The graph shows a normal (Y) and abnormal (Z) relationship of bicarbonate to pH in the blood. Which of the following is the most likely cause of a shift from point Y to point Z in a healthy subject?

A 73-year-old woman has a 3-month history of increasing fatigue, weakness, and a 9.0-kg (20-lb) weight loss. Examination shows hepatosplenomegaly. An M-protein spike is observed on serum electrophoresis. Which of the following is the most likely diagnosis?

A 12-year-old girl is brought to the physician by her parents because of a 2-day history of dizziness and headache. She is intelligent and does well in school. Her mother had a cerebellar tumor removed during childhood and is concerned that her daughter might have a similar condition. A normal reaction to which of the following physical examination maneuvers is most likely to rule out a cerebellar tumor in this patient?

A 7-year-old girl is brought to the physician by her mother because of increasingly severe left knee pain during the past 12 hours. Her temperature is 39.1 °C (102.3°F), pulse is 115/min, respirations are 18/min, and blood pressure is 110/60 mm Hg. Physical examination shows a tender, swollen left knee that is unable to be flexed because of pain. Hematologic studies show a leukocyte count of 35,000/mm3 and erythrocyte sedimentation rate of 120 mm/h. Which of the following is the most likely diagnosis?

A 75-year-old woman is brought to the physician because of a 1-day history of fever and back pain. Her temperature is 39.5°C (103.1°F), pulse is 111 /min, respirations are 32/min, and blood pressure is 115/79 mm Hg. Physical examination shows left-sided costovertebral angle tenderness. Laboratory studies show a leukocyte count of 17,000/mm3 (with 9% bands) and pyuria. Urine cultures grow Escherichia coli. It is determined that the patient’s fever is partially due to interleukin-6 (IL-6), which was induced by the IL-1 produced during the immune response. Which of the following best describes the role of IKB in the nuclear factor-kappa B (NF-KB) signal transduction pathway from IL-1 binding to IL-6 induction in this patient?

A 33-year-old woman comes to the physician because of a 2-week history of fatigue, difficulty swallowing, and paresthesias of her lips and fingers. She also has had episodes of painful wrist spasms during this period. She has Graves disease and underwent a surgical procedure to remove part of her thyroid gland 3 weeks ago. Her only medication is low-dose propranolol. Vital signs are normal. Physical examination shows no abnormalities except for a well-healing incision on the neck. An ECG shows a prolonged QT interval. Which of the following is the most likely cause of this patient’s new symptoms?

A 46-year-old man comes to the office because of a 1-year history of difficulty reading small print. He has no other history of vision difficulty. He has hypertension treated with hydrochlorothiazide. Pulse is 72/min, and blood pressure is 142/86 mm Hg; other vital signs are within normal limits. The pupils are 2 mm, equally round, and reactive to light and accommodation. Ocular movements are intact. On wall chart testing, visual acuity is 20/20 bilaterally. On handheld chart testing, he can read the 20/20 line only if he holds the card more than 14 inches away. Disc margins are sharp; there are no hemorrhages, exudates, or arteriolar narrowing. No other abnormalities are noted. Which of the following is the most likely diagnosis?

A 40-year-old woman who is a construction worker comes to the physician because of pain in her shoulder that developed after she lifted a heavy beam. Physical examination shows weakness and pain only during external rotation of the arm at the shoulder. There is muscle wasting inferior to the spine of the scapula. Which of the following muscles is most likely injured?

An autopsy is done on a 50-year-old man who died of pneumonia despite 5 days of antibiotic therapy in the intensive care unit. He had a 15-year history of alcoholism. A photograph of a sagittal section of the brain is shown. Based on this pathology, which of the following findings was most likely present on neurologic examination of the patient prior to his death?

The incidence of Haemophilus influenzae type b meningitis in children below age 2 years has decreased since the introduction of the current vaccination for this infection. This vaccine is composed of which of the following?

A 22-year-old man is brought to the emergency department 30 minutes after collapsing at home. He has a 3-year history of intravenous drug use. He appears confused. His temperature is 39.5°C (103.1 °F). Physical examination shows subungual hemorrhages of the fingers and jugular venous distention. A holosystolic murmur is heard at the lower left sternal border. Blood cultures are positive for Staphylococcus aureus. A chest x-ray shows multifocal airspace opacities. The most likely cause of these findings is infection of which of the following labeled cardiac valves in the CT scans of the chest?

A 49-year-old man comes to the emergency department because of a persistent and painful erection since he took a drug for erectile dysfunction 4 hours ago. His temperature is 37°C (98.6°F), and blood pressure is 110/65 mm Hg. Physical examination shows flushing of the skin and priapism. The most likely cause of this patient’s condition is a lack of input from which of the following neural pathways?