A 56-year-old man comes to the physician because of a 3-month history of a mild, nonproductive cough. He has a 20-year history of alcoholism. Physical examination shows no abnormalities. A PPD skin test result is positive. A chest x-ray and a Gram stain of induced sputum show no abnormalities. Treatment with isoniazid and a daily multivitamin is begun. The patient is compliant with the isoniazid therapy but not with the multivitamin supplementation. Two months later, he develops tingling and numbness of both feet. Deficiency of which of the following is the most likely cause of the foot symptoms in this patient?

Humoral antibody produced against many viruses following natural infection mediates protection against reinfection with the same strain primarily by which of the following mechanisms?

A 28-year-old woman at 32 weeks’ gestation comes to the physician because of a 4-day history of fever and back pain. She says that during this time she also has been crying frequently. Her temperature is 38°C (100.4°F). Physical examination shows costophrenic angle tenderness. The photomicrograph shown represents her disease. Which of the following mechanisms is the most likely cause?

An investigator is studying obesity in an adolescent population. Five thousand normal-weight patients are followed from the age of 10 years to the age of 15 years. At the conclusion of the study, 1100 patients meet the criteria for obesity. Which of the following best represents the incidence per 1000 patient-years of obesity during the course of this study?

A 21-year-old woman comes to the physician for a routine health maintenance examination. Her 3-year-old sister was recently diagnosed with cystic fibrosis. Prior to any genetic testing, which of the following best approximates this patient’s risk of being a heterozygote for cystic fibrosis?

A 52-year-old man with lung cancer comes to the physician for a follow-up examination. Smoking cessation has been recommended, but the patient says that he is unable to quit because he experiences a pleasurable sensation as he inhales the smoke. He has smoked 2 packs of cigarettes daily for 30 years. Which of the following mechanisms best explains how nicotine produces this sensation leading to addiction in this patient?

A sexually active 20-year-old woman has had painful, erythematous, vesicular lesions on the vulva for 2 days. Examination by speculum also shows lesions in the vaginal vault and on the cervix. A photomicrograph of a scraping of the base of an unroofed vesicle is shown. Which of the following is the most likely diagnosis?

A 98-year-old woman dies of respiratory failure. At autopsy, gross examination shows a small heart with a brown discoloration. Histologic examination of the cardiac tissue by light microscopy shows light brown pigment within the cardiac myocytes, particularly in the perinuclear region. This material does not stain positively for iron. Which of the following best describes this pigment?

An 8-year-old girl is brought to the physician for a well-child examination. Her mother says that she has been well except for an occasional cold. Her immunizations are up to date. She is at the 50th percentile for height and 60th percentile for weight. Physical examination shows breast bud development and a few pubic hairs. The mother asks whether her daughter’s development is normal. Which of the following is the most appropriate initial response by the physician?

A 67-year-old woman with Crohn disease is admitted to the hospital for bowel rest and parenteral hyperalimentation. A central venous catheter is placed. Seven days after admission, she develops a temperature of 39.2°C (102.6°F) and shaking chills. Broad-spectrum antibiotics are administered pending blood cultures. She continues to have daily temperature spikes. Two days later, blood culture grows yeast forms. Which of the following is the most likely causal organism?

A 25-year-old woman comes to the physician because of a 6-month history of a white discharge from her breasts. Her last menstrual period was 6 months ago. She has had no headaches or visual field changes. She has never been sexually active. Gentle palpation of both breasts produces expression of a milky discharge. Serum studies show:

A 5-day course of medroxyprogesterone fails to induce menses. An MRI of the brain shows an 8-mm lesion in the pituitary gland. The most appropriate treatment for this patient is a drug from which of the following classes?

An 11-year-old boy has had persistent pain in his right knee since he twisted it in a soccer game 3 weeks ago. Physical examination shows a tender area in the distal femur but no perceptible mass. An x-ray of the femur shows an osteolytic mass that has eroded through the cortex and elevated the periosteum; the mass is surrounded by reactive bone in some areas. Biopsy of the mass shows atypical cells with hyperchromatic pleomorphic nuclei. The cells are surrounded by an eosinophilic matrix, some of which is calcified. This tumor is most likely to spread first to which of the following areas?

A 28-year-old woman who works as a glassblower has recently sustained burns on her hands but feels little pain. Neurologic examination shows decreased pain sensation in both upper extremities and weakness and atrophy of the intrinsic muscles of both hands. Which of the following best explains these findings?

A 2-month-old girl is brought to the emergency department by her mother because of difficulty breathing for 8 hours. Physical examination shows cyanosis. A loud systolic murmur is heard. Laboratory studies show hypocalcemia and lymphopenia. Echocardiography shows tetralogy of Fallot. The diagnosis of DiGeorge syndrome is made, and a karyotype is ordered. Chromosomal analysis by high-resolution G-banding is reported as 46,XX. Which of the following genetic mechanisms is the most likely cause of this patient’s anomalies?

A 54-year-old woman with chronic kidney disease comes to the physician because of a 2-week history of itchy skin, increasingly severe nausea, and decreased urination. Current medications are hydrochlorothiazide and lisinopril. Her pulse is 80/min, respirations are 14/min, and blood pressure is 160/90 mm Hg. Physical examination shows no abnormalities except for excoriations from itching. Laboratory studies show:

Which of the following is the most likely cause of the findings in this patient?

A 25-year-old woman with a 3-year history of celiac disease comes to the physician because of a markedly itchy rash on her scalp, arms, buttocks, and legs for 5 weeks. Examination of the skin shows many crusted papules surrounded by excoriations over the upper and lower extremities and a few vesicles on the buttocks. A skin biopsy specimen shows the vesicles to be subepidermal. Direct immunofluorescence of the vesicles shows granular deposits of IgA in the epidermal-dermal junction. Which of the following is the most likely diagnosis?

A 27-year-old primigravid woman at 36 weeks’ gestation comes to the physician for a prenatal visit. Physical examination shows a uterus consistent in size with a 33-week gestation, so the patient is referred for ultrasonography, which shows normal fetal measurements. The ultrasonography shown is an image of the male fetal scrotum; the testes are indicated by the arrows. Which of the following is the most likely underlying cause of this finding?

A healthy 24-year-old woman participates in a study to determine the role of ghrelin in appetite. She is given free access to food during the study. The graph shows plasma concentrations of ghrelin in the woman during the study period. Which of the following labeled points on the curve most likely represents the consumption of a meal?

A 5-month-old girl is brought to the physician because of a 3-day history of “floppiness” when she sits. She also has had difficulty feeding and irritability since the age of 1 month. She is at the 3rd percentile for length, 50th percentile for weight, and 3rd percentile for head circumference. Her temperature is 36°C (96.8°F), pulse is 100/min, respirations are 29/min, and blood pressure is 80/50 mm Hg. Neurologic examination shows bilateral horizontal nystagmus, decreased extensor tone, hyperreflexia, and ankle clonus. Babinski sign is present bilaterally. Respiratory chain enzyme studies on cultured fibroblasts show decreased complex II activity. The most likely cause of these findings is a defect in which of the following processes?

An investigator is studying a T-lymphocyte clone that recognizes a peptide from the hemagglutinin glycoprotein of influenza virus bound by class II human leukocyte antigen. This clone most likely recognizes a peptide that was combined with a human leukocyte antigen in which of the following cellular compartments?

A newborn born at 36 weeks’ gestation dies 3 days later. The photograph shown is of a section of brain as seen at autopsy. Which of the following is the most likely underlying disease?

A 67-year-old woman has had decreased pain and temperature sensation in the left lower extremity for 1 week. The most likely cause is damage to which of the following labeled sites in the cross section of the spinal cord?

A 50-year-old woman is brought to the emergency department 20 minutes after the sudden onset of pain in her epigastrium that radiates to her back and is associated with nausea. She has a history of cholelithiasis. She appears restless. Her temperature is 37.6°C (99.7°F), pulse is 120/min, and blood pressure is 115/60 mm Hg. Abdominal examination shows distention with rebound tenderness and guarding. The pain is partially relieved when the patient bends forward. A CT scan of the abdomen shows fluid surrounding the pancreas. Obstruction of which of the following is the most likely cause of the findings in this patient?

A 65-year-old man dies of renal failure. Urinalysis shows:

At autopsy, the kidneys are found to be enlarged. A histologic section of renal tissue is shown in the photomicrograph. Which of the following is the most likely diagnosis?

A 78-year-old man is brought to the emergency department after falling from a ladder. On arrival, he is lucid. Physical examination shows a severe scalp contusion and laceration. Neurologic examination shows no abnormalities. On the second day, he is stuporous and has a headache. Examination shows slight weakness, hyperreflexia, and an extensor plantar reflex, all on the right. A CT scan of the head is shown. The most likely cause of these findings is trauma to which of the following vascular structures?

A 1-year-old boy is brought to the physician for a well-child examination. The mother is concerned because her son’s fine, pale hair has not changed color since birth. His eyes are blue. During ophthalmologic examination, the patient turns away from the flashlight and starts crying. Which of the following is the most likely cause of the pale skin color in this patient?

A 38-year-old man comes to the physician because of a 1-week history of a discharge from his penis and testicular pain. He is sexually active and uses condoms inconsistently. Physical examination shows a thick green urethral discharge and exquisite tenderness of the right testis. The pain is relieved by elevation of the scrotum. A photomicrograph of a Gram stain of the discharge is shown. Which of the following is the most likely causal organism?

A 43-year-old woman has had increasing fatigue, intolerance to cold, and dry thickened skin for 7 weeks. The thyroid gland is firm, nodular, and diffusely enlarged. Examination of tissue obtained on biopsy of the thyroid gland shows a diffuse infiltration of lymphocytes with occasional lymphoid follicles. Which of the following is the most likely diagnosis?

A 67-year-old woman with acute myelogenous leukemia develops fever and chills 6 days after undergoing induction therapy. Her temperature is 38.3°C (100.9°F), and blood pressure is 110/60 mm Hg. Physical examination shows scattered petechiae over the upper and lower extremities and trunk. Laboratory studies show a leukocyte count of 100/mm3 (98% lymphocytes and 2% monocytes) and platelet count of 4000/mm3. Blood cultures grow Pseudomonas aeruginosa. A deficiency of which of the following is the most likely predisposing factor for development of bacteremia in this patient?

A 24-year-old woman comes to the physician for an examination prior to employment. Physical examination shows no abnormalities. An ECG shows a sinus rhythm of 70/min, PR interval of 152 msec, and QRS complex of 84 msec; there are no ectopic beats. Which of the following best represents the longest conduction time in this patient?

A study is conducted to assess the effect of a new selective estrogen receptor modulator (SERM) on bone fractures. Two thousand women with a history of vertebral fracture and 5000 women with no fracture history are randomly assigned to a placebo or to SERM at a dose of 60 mg or 120 mg. The graph shows the percent of women who had a new fracture during 5 years of follow-up (± standard error of the mean). Which of the following is the most accurate conclusion about preventing new fractures based on these data?

An 18-year-old man comes to the physician because of nonpitting facial edema and difficulty breathing several hours after a dental procedure. He has a history of unexplained episodes of abdominal pain. His serum C2 concentration is found to be markedly decreased. Which of the following best explains this patient’s illness?

A 24-year-old man who is comatose is admitted to the hospital because of a drug overdose and pneumonia. On admission, he is intubated and mechanically ventilated. While receiving a tidal volume of 500 ml_, the patient’s end-expiratory pressure is +5 cm H20, and his end-inspiratory airway pressure is +25 cm H20. An esophageal balloon is inserted, and an end-inspiratory pleural pressure of +20 cm H20 is measured. Which of the following best represents this patient’s respiratory system compliance?

A 54-year-old man with a 1-year history of multiple sclerosis has increasingly painful muscle spasms. An agonist that acts at which of the following receptors is most likely to alleviate the increased extensor tone and clonus?

A 43-year-old woman comes to the physician because of a 4-week history of intermittent episodes of severe abdominal pain, especially after eating fatty foods. Physical examination shows no abnormalities. Abdominal ultrasonography shows several 3- to 4-mm gallstones contained within the gallbladder. The patient declines surgery. A drug with which of the following mechanisms of action is most appropriate for this patient?

A 23-year-old man cuts his lip inadvertently while shaving. Seconds after the injury, the bleeding nearly stops. Which of the following mechanisms is the most likely cause of the early rapid control of blood loss in this man?

A 74-year-old man comes to the office because of a 3-week history of progressive shortness of breath with exertion. He has had difficulty climbing one flight of stairs. He also has a 20-year history of poorly controlled hypertension, for which he rarely takes his prescribed medication, and osteoarthritis treated with naproxen daily. His temperature is 37.1 °C (98.8°F), pulse is 76/min, respirations are 20/min, and blood pressure is 180/98 mm Hg. Pulse oximetry on room air shows an oxygen saturation of 92%. Physical examination shows 10-cm jugular venous distention above the sternal angle. Crackles are heard over both lung bases. An S4 is heard. Echocardiography shows a normal ejection fraction. Which of the following best explains this patient’s symptom?

One thousand office workers are surveyed to determine whether or not they use computers and whether or not they have symptoms of carpal tunnel syndrome. Which of the following best describes this study?

A 68-year-old man with recurrent urinary tract infections comes to the physician because of a 2-day history of fever and pain with urination. Urinalysis shows pus. He is treated with levofloxacin. His symptoms worsen, and a blood culture grows Pseudomonas aeruginosa that is resistant to levofloxacin. Alteration of which of the following best explains the resistance of P aeruginosa to levofloxacin in this patient?

A 7-year-old girl is brought to the physician because of a 2-week history of painful swelling under her right arm, which has become increasingly severe during the past 3 days. Physical examination shows a 2 x 1 -cm, tender, right axillary lymph node and a small papule on the dorsum of the right hand. A silver-stained biopsy specimen of the papule shows pleomorphic bacilli. Which of the following is the most likely causal organism?

A 68-year-old woman has had progressive shortness of breath with exertion since she started treatment with eyedrops for glaucoma 2 weeks ago. Pulmonary function tests show a decreased forced expiratory volume in 1 sec (FEV.,). The lungs are clear to auscultation. The eyedrops are most likely from which of the following classes of drugs?

A 65-year-old man comes to the physician because of fever and a worsening cough productive of approximately cup of blood-tinged sputum daily. He has smoked 11/2 packs of cigarettes daily for 45 years. His temperature is 38.4°C (101.2°F), respirations are 20/min, and blood pressure is 140/90 mm Hg. Physical examination shows bilateral clubbing of the digits. Pulmonary examination shows egophony, whispered pectoriloquy, and dullness to percussion in the area overlying the 2nd and 3rd ribs on the right anteriorly, just inferior to the right clavicle. Which of the following structures is the most likely site of an obstructing carcinoma?

A physician is sad because he has to inform a patient of recent test results that indicate progression of carcinoma to the terminal phase. When the patient sees the physician’s face, he begins to cry and says, “It’s bad news, isn’t it?” Which of the following responses by the physician is most appropriate?

The tracing shows contractile responses of a skeletal muscle preparation to electrical stimulation at five different frequencies. The amount of calcium sequestration in sarcoplasmic reticulum is highest during which of the following labeled responses?

An 18-year-old woman with mild intellectual disability is brought to the physician because of a 3-day history of decreased ability to see in reduced light. She has a lifelong history of chronic diarrhea. Two years ago, she developed a lack of muscle control of her arms and legs, and generalized weakness. Her 16-year-old brother has had similar symptoms. Ophthalmologic examination shows bilateral retinitis pigmentosa. There is ataxia and loss of deep tendon reflexes. Laboratory studies show erythrocytes with spiny projections and a serum total cholesterol concentration of 40 mg/dL. Which of the following apolipoproteins is most likely deficient in this patient?

A 13-year-old boy is scheduled to receive chemotherapy for a leukemia that has the histologic features of malignant lymphocytes. This neoplasm is further typed for cell surface and intracellular markers specific for lymphocyte subsets. The neoplastic cells do not express the following markers: CD4, CD8, surface IgM, surface IgG, cytoplasmic IgM and μ-heavy chain, cytoplasmic IgG, and γ-heavy chain. The leukemic cells express class I MHC molecules and show rearrangement of the T-lymphocyte receptor β-chain gene D and J segments. Which of the following is the normal counterpart of these malignant lymphocytes?

A 3-year-old girl has a history of recurrent infections. In vitro, neutrophils isolated from this patient are capable of phagocytosis and can kill Lactobacillus species but not Staphylococcus aureus. This patient most likely has a defect involving which of the following enzymes?

A 23-year-old woman is admitted to the hospital after taking an overdose of 16 acetaminophen tablets. She ingested the acetaminophen after she broke up with her boyfriend of 2 months. She has been admitted to the hospital several times during the past 5 years for treatment of suicide attempts and other self-harm attempts. Her history includes childhood sexual abuse, and she has difficulty holding a job. She tells the physician that she has received substandard care from this hospital in the past. She says, “But now that you’re my physician I know I’m going to get better. I can tell because we have a connection.” Her affect is bright and cheerful. This patient most likely has which of the following types of personality disorders?

A 33-year-old man comes to the physician because of intermittent numbness and pain of his right arm during the past 6 months. His blood pressure is 120/80 mm Hg in both upper extremities; the pulse examination shows no abnormalities. A chest x-ray shows a right complete cervical rib. A CT scan of the neck and chest shows compression of the brachial plexus. Which of the following vessels is at greatest risk for injury during operative removal of the right cervical rib?

A 45-year-old man is brought to the physician because of a 4-week history of mild confusion, memory difficulties, generalized muscle aching, and intermittent tingling of his lips and fingers. He says he has been sleeping more than usual, and that he feels “down in the dumps.” Vital signs are normal. Physical examination shows no abnormalities except for dry, scaly skin and dry hair. Tapping with a reflex hammer over the left side of the face just anterior to the ear causes left facial muscle contractions. Which of the following is the most likely diagnosis?