The diagram depicts a cardiac murmur heard in a healthy 92-year-old man. Which of the following age-related processes is responsible for the murmur?

Following blockage of a cerebral artery, the neurons that die from hypoxia release a neurotransmitter that promotes excessive calcium influx, lysis, and cell death in nearby undamaged neurons. Which of the following substances is the primary cause of this cascade of excitotoxicity?

A 28-year-old woman comes to the physician because of a 4-day history of palpitations, severe neck pain, fatigue, and malaise. Her pulse is 120/min and regular. Physical examination shows a diffusely tender, mildly enlarged thyroid gland. There is no exophthalmos. Serum studies show a thyroid-stimulating hormone concentration of 0.01 pU/mL. Which of the following is the most likely diagnosis?

A 60-year-old woman is receiving cisplatin therapy for advanced transitional cell bladder cancer. She develops paresthesias, and the medication is stopped. The medication likely damaged the largest cells in the region labeled “B” in the drawing of the spinal cord shown. The damage to these cells would most likely lead to which of the following motor signs?

An investigational drug (Drug X) under development for the treatment of hypertension is being tested in phase 1 clinical trials. A significant number of subjects develop dose- dependent increases in serum AST and ALT activities. The investigators hypothesize that this effect is due to oxidative stress. Assuming that biopsy samples of the liver can be obtained from the subjects, which of the following would be the best measure of hepatic oxidative stress caused by Drug X?

A study is conducted to assess the relationship between angiotensin gene polymorphisms (I versus D alleles) and the development of progressive renal disease due to IgA nephropathy. A total of 250 patients are enrolled: 125 patients with progressive renal disease due to IgA nephropathy (Group X) and 125 patients with IgA nephropathy with stable renal disease (Group Y). Results show that 67 patients in Group X have the D allele, whereas 12 patients in Group Y have the D allele. Which of the following tests is most appropriate to determine whether there is a significant difference in the prevalence of the D allele between these two groups?

A 68-year-old man comes to the physician because of a 1-month history of not being able to sustain an erection for sexual intercourse, although he has no difficulty during masturbation. His wife of 40 years died 2 years ago after a prolonged illness. He began dating recently. He has a multinodular goiter but takes no medications. His serum thyroid- stimulating hormone concentration is 4.0 pU/mL, and serum testosterone concentration is within the reference range. He does not have any symptoms of major depressive disorder. Which of the following pairs of additional findings is most likely to be found on history taking?

A 56-year-old man comes to the physician because of a 3-month history of intermittent regurgitation of material with an acidic taste. He is unable to sleep and has missed 3 days of work during the past month because of the symptom. Various non-pharmacologic measures, including elevating the head of his bed and decreasing his dietary fat intake and portion size, have resulted in only mild improvement. Physical examination shows no abnormalities. Esophageal endoscopy shows severe erosions; there are no other structural abnormalities. The most appropriate pharmacotherapy for this patient is a drug with which of the following mechanisms of action on the parietal cells?

A 65-year-old man with diabetes mellitus develops a neuropathy of the cranial nerve indicated by the arrow in the normal brain stem. Which of the following is the most likely associated functional deficit?

A study is conducted to evaluate the effectiveness of cough medication in children. A total of 120 patients under the age of 12 years who have been diagnosed with a viral upper respiratory tract infection are randomly selected to receive dextromethorphan or no treatment. The participants were recruited from several emergency departments in an urban area. Parents complete a rating scale for their children’s cough at baseline and 1 day after receiving dextromethorphan or nothing. The results show a statistically significant improvement in cough scores for patients receiving dextromethorphan (p=0.04) compared with children receiving no treatment. Which of the following is the most significant limitation to the internal validity of this study?

A 50-year-old woman from Egypt comes to the physician because of painless blood in her urine for 2 weeks. Urinalysis is within the reference range. Urine cytologic findings show malignant squamous epithelial cells. Which of the following is the strongest predisposing risk factor for this type of tumor?

A 62-year-old man has had petechiae and easy bruising for the past month. He has a 2-year history of alcoholic cirrhosis with portal hypertension. Laboratory studies show:

Which of the following is the most likely cause of the pancytopenia?

A 27-year-old man has hepatomegaly and mild jaundice. Serum alkaline phosphatase and y-glutamyltransferase activities are increased. Which of the following properties of these enzymes allows them to be used to detect defects in bile flow?

A 56-year-old man comes to the physician for a routine examination. His stool is positive for occult blood. Colonoscopy shows a pedunculated growth that is coarsely lobulated and 1.4 cm in diameter. The excised lesion is covered by colonic epithelium and composed of branching glands lined by tall hyperchromatic cells. Some areas appear mildly dysplastic, but there is no evidence of invasion of the stalk. Which of the following oncogenes is most likely to be activated in this lesion?

A 22-year-old woman of Irish descent is brought to the emergency department because of a 1 -hour history of severe pain and coldness of her left leg. She has an IQ of 80, and she dropped out of high school in the tenth grade. Her parents and two older siblings have normal intelligence and have no history of these symptoms. Ophthalmologic examination shows a partially dislocated lens in the right eye. Physical examination shows mottling and loss of pulses in the left lower extremity and foot. Arteriography of the left lower extremity shows thrombosis of the femoral artery. This patient most likely has a metabolic disorder involving which of the following amino acids?

A 38-year-old man with a 3-year history of type 2 diabetes mellitus comes to the physician for a follow-up examination. In addition to taking an oral antihyperglycemic agent, he has tried controlling his condition with diet modifications and exercise. He is 188 cm (6 ft 2 in) tall and weighs 113 kg (250 lb); BMI is 32 kg/m2. Physical examination shows no other abnormalities. His hemoglobin A1c is 10%. The physician recommends initiation of insulin injections to obtain better control over the patient’s blood glucose concentration. The patient responds, “I know that insulin would help control my blood sugar. But a lot of people in my family have diabetes, and insulin made them really sick at times.” This patient is most likely at which of the following stages of change regarding insulin administration?

A 2-year-old boy has had recurrent bacterial infections with markedly increased absolute neutrophil counts in the blood (30,000-150,000/mm3). Studies of neutrophils show:

Which of the following is the most likely diagnosis?

A 42-year-old man has an autoimmune disorder resulting in proximal muscle weakness of the lower extremities. Arrows in the photomicrograph shown indicate membranes that contain high concentrations of channels that are targeted by this condition. Which of the following is the most likely diagnosis?

A 16-year-old boy has a 6-month history of type 1 diabetes mellitus and requires daily insulin injections. His blood glucose control has been poor recently, which the physician suspects may be related to the patient’s reluctance to self-administer insulin. Which of the following questions is most appropriate to broach this issue with the patient?

A 64-year-old man with a 25-year history of alcoholism is brought to the emergency department by his wife because of a 1 -day history of confusion. He is disoriented and disheveled. His pulse is 110/min, respirations are 20/min, and blood pressure is 100/64 mm Hg. Physical examination shows signs of dehydration and jaundice, and spider angiomata over the face and chest. There is a flapping, up-and-down motion of the hands when the upper extremities are outstretched horizontally. Abdominal examination shows distention with bulging flanks and shifting dullness. In addition to other appropriate pharmacotherapy, administration of oral neomycin is begun. Which of the following primary mechanisms of action is most likely to occur in this patient as a result of this drug treatment?

A 42-year-old man comes to the physician because of a 1-week history of a diffuse, painless rash on his back. He first noticed the rash after he spent a week sunbathing at the beach. He says the rash does not itch. A photograph of the rash is shown. Which of the following is the most likely causal organism?

A 6-year-old boy is brought to the emergency department because of coughing, wheezing, and rapid breathing for 6 hours. He was diagnosed with an upper respiratory tract infection 2 days ago. His temperature is 37.2°C (99°F), pulse is 120/min, respirations are 44/min, and blood pressure is 90/60 mm Hg. Inspiratory and expiratory wheezes are heard throughout the lung fields. There is decreased tactile fremitus. Which of the following is the most likely diagnosis?

The graphs show the combined effect of total serum cholesterol concentration and diastolic blood pressure on age-adjusted coronary artery disease death rates for both smokers and nonsmokers. Two persons, X and Y, have the following data:

Compared with X, which of the following is the relative risk of dying from coronary artery disease for Y?

A 32-year-old woman comes to the physician because of a 3-month history of fevers, weakness, and night sweats. Physical examination shows enlarged axillary lymph nodes. A photomicrograph of tissue obtained on biopsy of an affected node is shown. A stain for acid-fast bacilli is negative. Which of the following is most likely involved in the pathogenesis of these findings?

An 18-month-old girl is brought to the physician because of failure to thrive and frequent wet diapers. She is at the 3rd percentile for length and weight. Physical examination shows dehydration, decreased muscle tone, and bowing of the legs. Slit lamp examination shows crystals in the corneas. Serum studies show hypophosphatemia, hypokalemia, and a nonanion gap metabolic acidosis. Urine studies show a pH of 5, glucosuria, phosphaturia, and generalized aminoaciduria. Which of the following is the most likely cause of the metabolic acidosis in this patient?

A 45-year-old woman with chronic myelogenous leukemia comes to the physician for a follow-up examination. Physical examination shows pallor and bleeding gums. Laboratory studies show a leukocyte count of 90,000/mm3 (60% blasts) and a platelet count of 27,000/mm3. A drug regimen of mitoxantrone, vinblastine, and thioguanine is initiated, with no improvement. During the last cycle of scheduled treatment, a sample of the blast cells is harvested, and the intracellular concentrations of mitoxantrone and vinblastine in these blast cells are found to be undetectable. An increase in which of the following mechanisms best explains this observation?

An investigator is studying Helicobacter pylori strains isolated from the same patient over several years. The immune response to proteins produced by these strains is observed. It is found that the original H. pylori isolate from the patient expresses one protein recognized by the patient’s antibodies, but subsequent isolates do not express this protein. Sequencing of the gene encoding the protein from the original and subsequent isolates is done. It is found that subsequent isolates have nine consecutive cytidine residues, whereas the original isolate has eight. The results are shown.

Which of the following mechanisms best explains the genetic change?

A 56-year-old man with esophageal varices who is awaiting liver transplantation undergoes placement of a transjugular portosystemic shunt. During the procedure, a catheter with a stent is threaded through the right internal jugular vein and down through the vena cava to the liver. To relieve the portal hypertension via this route, the stent should be placed between a branch of the portal vein and which of the following additional veins?

An 11-year-old boy receives succinylcholine and sevoflurane for anesthesia during surgical repair of a hernia. During the procedure, the patient develops muscle rigidity, tachycardia, hyperkalemia, hypocalcemia, and hyperthermia. This patient most likely carries a variant form of the gene coding for which of the following?

A 35-year-old woman comes to the emergency department 3 hours after the sudden onset of severe right-sided back pain. She has a history of recurrent urinary tract infections. Her most recent infection was 1 month ago; she was successfully treated for Klebsiella pneumoniae with antibiotics. The patient is not taking any medications. She says that she has been eating more fast food and drinking less water during the past month because of a busy schedule. She is sexually active and uses a spermicidal cream for contraception. Her temperature is 37°C (98.6°F), pulse is 100/min, respirations are 14/min, and blood pressure is 138/66 mm Hg. Physical examination shows marked tenderness to palpation over the right flank. Urinalysis shows:

An excess of which of the following is the most likely underlying cause of this patient’s flank pain?

A 6-year-old girl is brought to the physician for a follow-up examination tubular acidosis was made at the age of 2 years. Physical examination She has been receiving treatment with potassium citrate monohydrate since the diagnosis of renal shows no abnormalities. Serum studies show:

A defect in renal ammoniagenesis is suspected. Which of the following substrates is the most likely source of ammonia production in this patient?

A 47-year-old woman comes to the physician because she wants to “do something about my wrinkles.” Physical examination shows fine wrinkles in photodamaged skin on the face. Treatment with tretinoin is started. Collagen synthesis will most likely be increased in this patient by which of the following mechanisms?

A 46-year-old woman comes to the office because of a 3-month history of fever, malaise, and easy bruising. Her mother and maternal grandmother died of breast cancer at the ages of 49 and 52 years, respectively. Her temperature is 38°C (100.4°F), pulse is 115/min, respirations are 16/min, and blood pressure is 125/90 mm Hg. Physical examination shows numerous large ecchymoses over the trunk and lower extremities. Laboratory studies show an increased leukocyte count with immature segmented neutrophils. Genetic testing shows the presence of the Philadelphia (Ph1) chromosome. Which of the following best explains this patient’s current condition?

A 50-year-old man comes to the physician because of a 2-week history of progressive shortness of breath while climbing stairs to his office every morning. He reports no other problems, but he is concerned because his father had a major myocardial infarction at the age of 52 years. His pulse is 110/min and regular, respirations are 16/min, and blood pressure is 135/95 mm Hg. The lungs are clear to auscultation. Cardiac examination shows normal heart sounds with a physiologic split of S2. Stress echocardiography shows hypokinesis of the posterior left ventricle with increasing activity levels. Which of the following is the most likely cause of the posterior left ventricular findings in this patient?

An investigator attempting to develop a vaccine for gonorrhea produces an attenuated organism that he administers to female rats as an inhaled aerosol. Swabs of vaginal secretions show a significant increase in antibodies specific for gonorrheal antigens. Which of the following mechanisms best accounts for this immune response in the genital tract?

A 68-year-old woman is brought to the emergency department 3 hours after falling onto her right wrist while working in her yard. Examination of the right wrist shows swelling and ecchymoses. Passive flexion of the right wrist exacerbates the pain. An x-ray of the right wrist is shown. Which of the following is the most likely cause of these findings?

A 44-year-old woman comes to the physician because of a 3-week history of severe headache. She is 157 cm (5 ft 2 in) tall and weighs 86 kg (190 lb); BMI is 35 kg/m2. Funduscopic examination shows papilledema. An MRI of the brain shows no abnormalities. A lumbar puncture is done. Cerebrospinal fluid (CSF) analysis shows an opening pressure of 32 cm H20. In addition to recommendations regarding dietary changes and weight loss, treatment with acetazolamide is begun. This drug will most likely improve the patient’s symptoms by which of the following mechanisms?

An 8-year-old girl is brought to the physician by her parents because of abdominal pain for 3 days. She is at the 90th percentile for height and the 80th percentile for weight. Breast, pubic hair, and axillary hair development is Tanner stage 3. Pelvic examination shows a firm, smooth, right ovarian mass. Ultrasonography of the abdomen confirms the presence of an 8-cm-diameter ovarian mass. Which of the following types of ovarian lesions is most likely in this patient?

The higher incidence of birth defects in children born to women more than 35 years old may be the result of environmental influences on chromosomes in developmental arrested oocytes at which of the following stages of cell division?

A 36-year-old man who is heterozygous for an LDL-receptor deficiency has a total serum cholesterol concentration of 330 mg/dl_. After taking a drug that inhibits cholesterol synthesis, his total serum cholesterol concentration decreases to 200 mg/dL. Which of the following proteins would be upregulated as a result of drug therapy?

In biosynthesis of thyroid hormones, iodide is concentrated by the thyroid gland and oxidized by thyroidal peroxidase to iodine. Iodine iodinates amino acid residues within the thyroglobulin molecule. Which of the following amino acids undergoes iodination?

A 50-year-old man collapses and dies while running to catch an airplane. A photograph of his aortic valve is shown. Which of the following best describes the lesion?

A previously healthy 42-year-old Asian woman is brought to the emergency department because of a 24-hour history of nausea, vomiting, and progressive lethargy. She has smoked 1 pack of cigarettes daily for 25 years and drinks four glasses of wine daily. She uses high-dose acetaminophen daily for headaches. She does not use illicit drugs. She is 155 cm (5 ft 1 in) tall and weighs 50 kg (110 lb); BMI is 21 kg/m2. She is responsive to painful stimuli. Initial laboratory studies show increased hepatic aminotransferase. Which of the following effects of alcohol most likely contributed to this patient’s condition?

A 20-year-old woman comes to the physician because her menstrual period is 1 week late, intercourse with her boyfriend 20 days ago. A urine pregnancy test result is positive. Which Menses had occurred at regular 28-day intervals. She had unprotected of the following best describes the stage of development of the embryo sexual at this time?

During a genome project, an experimental animal is found to have a DNA sequence with similarities to a growth hormone receptor. Which of the following peptide segments shown is the transmembrane segment?

A 36-year-old man comes to the physician’s office without an appointment and demands to be seen immediately. He has had a sore throat for 24 hours and explains his problem is more important than the other patients’ because he is a vocalist. He is extremely upset when the receptionist explains he will need to wait for 1 hour to see the physician. He talks with her constantly while he waits. He says, “My wife and I split like 3 months ago. We have a 6-month-old boy, but she was just so into her pregnancy, she had no time for me. And she doesn’t really appreciate my music. I need full support from my lady. Especially when my band’s just about to make it big.” Which of the following is the most likely personality disorder?

A healthy 70-year-old woman has participated in a longitudinal study of the effects of aging on performance during pulmonary function tests for the past 50 years. She has undergone a complete set of tests, including arterial blood gas analyses, every 5 years. Which of the following sets of changes best represents this woman now compared with her results at the age of 20 years?

A 43-year-old woman comes to the physician because of a 6-month history of altered consciousness. During the interview, she stops talking in mid-sentence, turns her head to the right, and extends and stiffens her right upper extremity. She has a blank look and does not respond to any questions. She then has some repetitive lip smacking and picking movements of the hands. The episode lasts approximately 30 seconds. She slowly returns to her normal state during the next 4 to 5 minutes. The most likely diagnosis is which of the following types of seizures?

While digging in the forest, an archaeologist finds the skeleton of a child in a shallow grave. Examination of the skull shows frontal bossing; there is delayed eruption of the teeth and abnormal enamel formation of those teeth that are erupted. The spine and arm bones show no abnormalities. The tibias show marked bowing. Which of the following was the most likely cause of this child’s skeletal defects?

A 2-month-old boy is brought to the physician because of a 7-day history of hoarseness. His mother has AIDS and used cocaine throughout her pregnancy. Physical examination shows no abnormalities. A fiberoptic laryngoscopic examination shows a nodule on the left vocal cord. Which of the following viruses is the most likely cause of this nodule?