1. A 44-year-old obese man has extremely high plasma triglyceride levels, but cholesterol levels are within normal limits. Following treatment with a drug specifically indicated for hypertriglyceridemia, triglyceride levels decrease to almost normal. Which of the following agents is most likely to have caused this desired change?

A. Atorvastatin

B. Cholestyramine

C. Colestipol

D. Ezitemibe

E. Gemfibrozil

The answer is E.

EXPLANATION: Gemfibrozil mainly lowers triglycerides and is used specifically for that purpose. This fibric acid derivative is sometimes classified as a peroxisomal proliferator-receptor activator (PPAR). It stimulates lipoprotein lipase synthesis and hydrolysis of triglycerides in chylomicrons and VLDL. The net effect is increased clearance of triglycerides. Clofibrate is a related (but lesser used) fibrate. As you should recall, atorvastatin (a; and other statins) inhibits cholesterol synthesis by inhibiting HMG CoA reductase, and depending on a host of factors they may or may not lower triglycerides; cholestyramine (b) and colestipol (c) are bile acid sequestrants; ezetimibe (d), a relatively new drug, inhibits uptake of dietary cholesterol from the gut. Those other drugs may have beneficial effects on serum triglyceride levels, but they are not first-line drugs for managing hypertriglyceridemia with or without concomitant hypercholesterolemia.

2. A 27-year-old woman is diagnosed with hypercorticism. To determine whether cortisol production is independent of pituitary gland control, you decide to suppress ACTH production by giving a high-potency glucocorticoid. Which of the following glucocorticoids is the best for this indication?

A. Dexamethasone

B. Hydrocortisone

C. Methylprednisolone

D. Prednisone

E. Triamcinolone

The answer is A.

EXPLANATION: Of the drugs listed, dexamethasone is by far the most potent in terms of relative glucocorticoid effects. The dexamethasone suppression test has several uses: it allows not only complete suppression of pituitary ACTH production, but also accurate measurement of endogenous corticosteroids, such as 17-ketosteroids, in the urine. The small amount of dexamethasone present contributes minimally to this measurement. None of the other drugs listed would be suitable for this test, and all are less potent than dexamethasone.

3. A 50-year-old man is well aware of the benefits of aspirin in terms of reducing the risk of death from an acute myocardial infarction, mainly because he has seen and carefully studied many of the ads and internet posts about this. He notices that the usual recommended dose of aspirin for cardioprotection is 81 mg/day, but reasons that the bigger the dose, the bigger the protective effect. He has taken "at least" 1000 mg of aspirin twice a day for the last 6 months. While he is fortunate in terms of having no apparent gastrointestinal adverse effects, he suffers an MI. Autopsy results show considerable platelet occlusion of several coronary vessels. Which of the following most likely explains the mechanism by which aspirin triggered these events?

A. Acetylated platelet glycoprotein IIb/IIIa receptors, triggering aggregation

B. Favored adhesion of platelets to the vascular (coronary) endothelium

C. Ruptured atherosclerotic plaque in the coronaries, exposing platelets to collagen

D. Suppressed hepatic synthesis of vitamin K–dependent clotting factors

E. Triggered excessive activation of platelets by ADP

The answer is B.

EXPLANATION: At the usual low cardioprotective doses of aspirin, the main effect of the drug is rather selective inhibition of thromboxane A2 (TXA₂) synthesis via the COX-1 pathway. Recall that TXA₂ is a major—but not the only—trigger of platelet activation, amplification, and aggregation. However, at high(er) doses, aspirin also inhibits synthesis of other eicosanoids, of which PGI₂ (prostacyclin), synthesized in the vascular endothelium, is of most importance here. Endothelial prostacyclin synthesis helps prevent platelets from adhering to the vascular wall. Suppress PGI₂ in the endothelium, and platelet adherence is increased, despite the fact that platelet TXA₂ synthesis has already been blocked. It's important to remember here that aspirin does nothing to inhibit platelet activation by such other agonists as collagen or ADP. By lowering endothelial PGI₂ levels we've increased the likelihood that platelets activated by eicosanoid-independent agonists will adhere to the lining of blood vessels, and potentially occlude them.

Aspirin has no effect on Gp IIb/IIIa receptors (a); it does not rupture or otherwise damage vascular plaques (c) to expose collagen; inhibit synthesis of any liver-based clotting factors (d); or amplify or otherwise enhance the effects of ADP (e) or of other platelet activators.

4. A 10-week-old infant is diagnosed with meningitis. A lumbar puncture reveals numerous neutrophils and gram-positive rods. She is admitted to the hospital and started on IV -lactams. Which of the following targets would most likely play a role in the development of resistance to the antibiotics?

A. Bactoprenol

B. DNA gyrase

C. Penicillin-binding proteins (PBPs)

D. Reverse transcriptase

E. RNA polymerase

The answer is C.

EXPLANATION: Transpeptidases or PBPs combine with penicillin to keep the final cross-linking step in the synthesis of peptidoglycan in the cell wall. All of the other choices are involved in polymerization processes. Examples of polymerization include the cell membrane (bactoprenol) and synthesis of DNA and RNA.

5. After a hemisection of the spinal cord takes place at T3, a patient experiences marked weakness in the right leg. Which of the following best accounts for this weakness?

A. There was muscle damage in the right leg

B. There was damage in his left frontal lobe

C. There was damage to the right corticospinal tract

D. The dorsal root was damaged

E. There was damage to the right femoral nerve

The answer is C.

EXPLANATION: The corticospinal tract mediates voluntary motor function. The fibers cross in the medullary pyramids; thus, lesions below this structure cause ipsilateral weakness. The reflexes are brisk, since in a UMN lesion there is a loss of inhibition to spinal reflexes. Muscle, dorsal root, and femoral nerve damage are all examples of lesions distal to the spinal cord. A frontal lobe lesion would not cause sensory or motor level damage, and would probably cause problems more proximally, including slurred speech.

6. A 36-year-old man sustains a gunshot wound to the left buttock. He is hemodynamically stable. There is no exit wound, and an x-ray of the abdomen shows the bullet to be located in the right lower quadrant. Which of the following is most appropriate in the management of his suspected rectal injury?

A. Barium studies of the colon and rectum

B. Barium studies of the bullet track

C. CT scan of the abdomen and pelvis

D. Angiography

E. Sigmoidoscopy in the ER

The answer is C.

EXPLANATION: A CT scan should be routinely requested for suspected rectal perforation. The use of rectal contrast with water-soluble radiopaque medium such as Gastrografin is helpful when reconstructing a bullet trajectory. The use of barium is contraindicated because its spillage in the peritoneal cavity mixed with feces would increase the likelihood of subsequent intra-abdominal abscesses. Instrumentation of the bullet track is also contraindicated because of the risk of injury to adjacent structures (eg, bladder, ureters, iliac vessels). Angiography is not a sensitive method for demonstrating injury of the intestinal wall. Rigid sigmoidoscopy should be used if the CT scan is suggestive but ambiguous.

7. A 37-year-old woman with a history of migraines presents to the ED complaining of crampy lower abdominal pain for 3 days. Workup reveals an intrauterine pregnancy and early prenatal care is arranged with obstetrics as an outpatient. You are concerned because her headaches are controlled with a significant number of medications. She uses medications for both abortive therapy and for prophylaxis. Which of the following classes of medications do you advise she discontinue while pregnant?

A. Anticonvulsants

B. Beta- Blockers

C. Triptans

D. Acetaminophen

E. Antiemetics

The answer is A.

EXPLANATION: Anticonvulsant medications are sometimes used as prophylaxis for migraines. Phenytoin, valproic acid, phenobarbital, and topiramate are among the antiepileptics commonly used to prevent migraines. Phenytoin causes fetal hydantoin syndrome, a constellation of birth defects, including growth retardation, cleft palates, hand deformities, and structural cardiac defects. Valproic acid has similar effects with the addition of neural tube defects. Phenobarbital, declining in its use for migraine prevention, causes cardiac defects, facial clefts, and urinary tract abnormalities. Early data on topiramate reveals teratogenicity in animal models.

-Blockers (b) are generally safe during pregnancy. There is significant controversy over the safety of using triptans (c) during pregnancy. The concern is that their vasoconstrictive properties might cause uterine vessels to constrict, limiting fetal blood flow. Most research has shown infants born to mothers taking triptans during pregnancy have rates of birth defects no higher than background. Hypertension and cardiac conditions are primary contraindications to triptan therapy, and the drug should be discontinued if early preeclampsia is suspected. Acetaminophen and antiemetics (d and e) are generally safe to take during pregnancy.

8. A 50-year-old salesman is on a yacht with a client when he has a severe vomiting and retching spell punctuated by a sharp substernal pain. He arrives in your emergency room 4 hours later and has a chest film in which the left descending aorta is outlined by air density. Which of the following is the most appropriate next step in his workup?

A. Contrast esophagram

B. Echocardiogram

C. Flexible bronchoscopy

D. Flexible esophagogastroscopy

E. Aortography

The answer is A.

EXPLANATION: The presence of air in the mediastinum after an episode of vomiting and retching is virtually pathognomonic of spontaneous rupture of the esophagus (Boerhaave syndrome). A contrast esophagram is the initial test of choice and is indicated with barium for a suspected thoracic perforation and water-soluble contrast (Gastrografin) for an abdominal perforation. Barium is inert in the chest but causes peritonitis in the abdomen, whereas aspirated Gastrografin can cause severe pneumonitis. CT scanning may be useful if a small, contained leak is suspected. A surgical endoscopy needs to be performed if the imaging studies are negative with a high degree of suspicion for an esophageal injury. If the leak is contained and the patient does not have any evidence of sepsis, then the leak can be managed with antibiotics and expectant management. For leaks associated with systemic signs, patients should undergo prompt surgical therapy. The operation of choice is dependent on the time to diagnosis. Leaks that are less than 24 hours old in patients without an underlying esophageal disorder may be managed with thoracotomy, repair, and drainage. Leaks older than 24 hours typically require more extensive surgery.

9. A 70-year-old woman is treated with sublingual nitroglycerin for occasional bouts of effort-induced angina. Which of the following best describes the mechanism by which nitroglycerin causes its desired antianginal effects, or a mediator involved in it?

A. Blocks -adrenergic receptors

B. Forms cyanide, much like the metabolism of nitroprusside does

C. Increases local synthesis and release of adenosine

D. Raises intracellular cGMP levels

E. Stimulates phosphodiesterase

The answer is D.

EXPLANATION: Nitric oxide is thought to be enzymatically released from nitroglycerin. It then reacts with and activates guanylyl cyclase to increase GMP, which in turn dephosphorylates myosin light chain kinase, causes calcium extrusion, and suppresses smooth muscle tone. Tolerance may develop in part from a decrease in available sulfhydryl groups. Autonomic receptors are not involved in the primary response of nitroglycerin, but compensatory mechanisms may counter the primary actions.

10. A 78-year-old male presents with loss of voluntary control of bladder functions. Which of the following conditions most likely accounts for the loss of bladder functions?

A. Loss of vagal and sacral efferent fibers only

B. Loss of vagal, sacral, and descending fibers from the cerebral cortex

C. Loss of lumbar and sacral efferent fibers only

D. Loss of lumbar, sacral, and descending fibers from the cerebral cortex

E. Loss of upper thoracic and cervical fibers only

The answer is D.

EXPLANATION: The smooth muscle of the bladder is innervated by postganglionic fibers of the sympathetic nervous system that arise from the inferior mesenteric ganglion. This ganglion, in turn, receives its inputs from T12–L2 of the intermediolateral cell column of the spinal cord. The smooth muscle of the bladder also receives inputs from postganglionic parasympathetic fibers that are innervated by preganglionic fibers arising from S2–S4. The external sphincter of the bladder (striated muscle) is innervated by ventral horn cells from the spinal cord. These ventral horn cells, in turn, receive inputs from supraspinal neurons that arise, in part, from the cerebral cortex. It is these neurons that form a part of the substrate for voluntary control over bladder functions (in combination with the parasympathetic and sympathetic fibers from sacral and lumbar levels, respectively).

11. A 34-year-old man reports a 1-day history of hematemesis. He feels well, but does describe occasional abdominal discomfort. He denies alcohol use. On examination, his abdomen is slightly tender without peritoneal signs. His stool is not bloody, but his fecal test for occult blood is positive. Which of the following is the most appropriate next step?

A. Gastric lavage

B. Barium study

C. Endoscopy

D. Red cell scan

E. Angiography

The answer is C.

EXPLANATION: Upper endoscopy is the best diagnostic testing option in the setting of an acute upper GI bleed. It can localize the source of bleeding, potentially allow therapeutic intervention, and allow for tissue diagnosis when necessary. Gastric lavage is less useful, and a barium study might interfere with subsequent intervention. Red cell scans are better to locate bleeding sources in the lower GI tract, and angiography may miss slower bleeds.

12. A patient has had progressive, chronic liver failure for the past 5 years. At the time of death, he would be expected to exhibit changes in which type of brain cells?

A. Oligodendrocytes

B. Striatal neurons

C. Pigmented cells of the substantia nigra

D. Astrocytes

E. Inferior olivary neurons

The answer is D.

EXPLANATION: Long-standing hepatic disease may produce a profound encephalopathy, but changes in the brain are notably sparse with portal-systemic encephalopathy. The most obvious change is an increase in Alzheimer type II astrocytes. These astrocytes are relatively large cells. Rarely patients show more dramatic changes, which include neuronal loss and focal necrosis. With chronic alcoholism and hepatic insufficiency, patients exhibit a loss of Purkinje cells in the cerebellum, but this is a consequence of alcohol toxicity or thiamine deficiency rather than of toxic injury from the hepatic dysfunction.

13. You are evaluating 34-year-old woman reports amenorrhea for 4 months. She has never been "regular," but has never gone this long without a period. Her laboratory evaluation is normal, including a negative pregnancy test. You give her medroxyprogesterone acetate (Provera) for 7 days, and the next week, she reports having a period. Which of the following is the most likely cause of her amenorrhea?

A. Premature ovarian failure

B. Ovarian neoplasm

C. Turner syndrome

D. Asherman syndrome

E. Polycystic ovarian syndrome

The answer is E.

EXPLANATION: The progestin challenge test separates patients with estrogen deficiency from those with normal or excess estrogen. Any bleeding in the week after the administration of Provera indicates that the patient has sufficient estrogen to menstruate, and that the amenorrhea is likely due to anovulation, as in polycystic ovarian syndrome. Those with premature ovarian failure would not have a withdrawal bleed. Neoplasm, Turner syndrome, and Asherman syndrome would not likely present in this way.

14. A 6-month-old child is brought to the emergency room after having a generalized seizure at home. She is found to have a temperature of 102.5°F (39.16°C). Which of the following correctly reflects why this patient should be investigated with a spinal tap?

A. All febrile seizures justify spinal taps.

B. Most febrile seizures are due to bacterial infections.

C. Febrile seizures cause increased intracranial pressure that must be relieved by withdrawing cerebrospinal fluid (CSF).

D. Intrathecal antiepileptics must be given.

E. Children this age may have meningitis with no manifestations other than fever and seizures.

The answer is E.

EXPLANATION: Between birth and 1 year of age, what appears to be a simple febrile seizure may actually be a seizure provoked by a bacterial meningitis. The agents most likely to be responsible in a 6-month-old child are Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis. Since the introduction of vaccination against H. influenzae, however, the incidence of meningitis due to this organism has been drastically reduced. Below 3 months of age, group B streptococci, Escherichia coli, and Listeria monocytogenes must also be considered. All require rapid diagnosis and early treatment if the child is to survive. Even though the child may not have substantial neck stiffness, the CSF will typically reveal glucose content less than two-thirds the serum level, elevated WBC count, and increased protein content. The responsible organism may be isolated and cultured, but treatment of the meningitis should begin before the organism is identified. A delay of hours in treatment may be lethal. Intravenous antibiotics should be started as soon as there is convincing evidence that febrile seizures are secondary to a bacterial meningitis. The drug chosen should be the one most effective against the most probable organism. The child's age, exposure, and symptomatology must all be considered in deciding what organism is most likely responsible for the infection.

15. A middle-aged man presents with congestive heart failure with elevated liver enzymes. His skin has a grayish pigmentation. The levels of liver enzymes are higher than those usually seen in congestive heart failure, suggesting an inflammatory process (hepatitis) with scarring (cirrhosis) of the liver. A liver biopsy discloses a marked increase in iron storage. In humans, molecular iron (Fe) is which of the following?

A. Stored primarily in the spleen

B. Stored in combination with ferritin

C. Excreted in the urine as Fe²⁺

D. Absorbed in the intestine by albumin

E. Absorbed in the ferric (Fe³⁺) form

The answer is B.

EXPLANATION: Ferrous iron (Fe²⁺) is the form absorbed in the intestine by ferritin, transported in plasma by transferrin, and stored in the liver in combination with ferritin or as hemosiderin. There is no known excretory pathway for iron, either in the ferric or ferrous form. For this reason, excessive iron uptake over a period of many years may cause hemochromatosis (235200), the likely diagnosis for this man. This is a condition of extensive hemosiderin deposition in the liver, myocardium, pancreas, and adrenals. The resulting symptoms include liver cirrhosis, congestive heart failure, diabetes mellitus, and changes in skin pigmentation.

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