1. We treat a patient with a drug that affects the clotting-thrombolytic systems for a time sufficient to let the drug's effects and blood levels stabilize at a therapeutic level. We then isolate platelets from a blood sample and test their in vitro aggregatory responses to ADP, collagen, PAF, and thromboxane A₂. Aggregatory responses to ADP are inhibited; responses to the other platelet proaggregatory agonists are unaffected. Which drug did we most likely administer to this patient?

A. Aspirin

B. Bivalirudin

C. Clopidogrel

D. Heparin

E. Warfarin

The answer is C.

EXPLANATION: Clopidogrel (and the lesser-used drug ticlopidine), is a noncompetitive antagonist of ADP. This prodrug (it must be metabolically activated) causes largely irreversible (i.e., for the lifetime of the platelet) inhibition of platelet aggregation by blocking ADP binding to the G_i-coupled P2Y(AC) receptor. It has no effect on platelet activation and amplification caused by such other proaggregatory agonists as collagen, thromboxane A2, thrombin, PAF, serotonin, or epinephrine.

Aspirin (a) inhibits platelet aggregation caused by thromboxane A2 (TXA2) only, and does so only by inhibiting TXA2 synthesis via cyclooxygenase, not by blocking TXA2 receptors.

Bivalirudin (b) is a synthetic hirudin derivative (you may recall that hirudin is produced by the medicinal leach, Hirudo medicinalis). It is classified as an anticoagulant, not as an antiplatelet drug. It is a direct-acting inhibitor of free and clot-bound thrombin, which leads to two main effects: (1) decreased conversion of fibrinogen to fibrin and (2) reduced activation of Factor XIIIa, which in turn decreases conversion of soluble fibrin monomers to insoluble (polymerized) fibrin.

Bivalirudin is given IV as an alternative to heparin (both drugs bind to free thrombin, but bivalirudin also interacts with clot-bound thrombin), mainly along with aspirin for patients with unstable angina who are undergoing angioplasty. It is also used to help treat heparin-induced thrombocytopenia and seems to be more effective than heparin when given post-myocardial infarction A–related drug is argatroban.

Heparin and warfarin (d, e) are anticoagulants, and have no direct effects on platelets. (You should also recall that since warfarin's site of action is the liver, it has no anticoagulant effects when tested in vitro.)

2. An 18-year-old male is shot in the back during a drive-by shooting. He is taken to the emergency room and a neurological examination reveals a hemisection of the right half of the spinal cord that extends from T8 to T12. Which of the following deficits will most likely result from this injury?

A. Loss of pain and temperature sensation from the right leg; loss of conscious proprioception from the left leg; UMN paralysis of the left leg

B. Loss of pain and temperature sensation from the left leg; loss of conscious proprioception from the right leg; UMN paralysis of the left leg

C. Loss of pain and temperature sensation from the left arm and leg; loss of conscious proprioception from the right leg and arm; flaccid paralysis of the right leg

D. Loss of pain and temperature sensation from the left leg; loss of conscious proprioception from the right leg; UMN paralysis of the right leg

E. Bilateral loss of pain and temperature sensation and conscious proprioception, both from the lower half of the body; UMN paralysis of the left leg and flaccid paralysis of the right leg

The answer is D.

EXPLANATION: Hemisection of the right side of the spinal cord that involves segments T8–T12 will result in contralateral loss of pain and temperature sensation below the level of the lesion and ipsilateral loss of conscious proprioception below the level of the lesion. Thus, this patient will experience loss of pain and temperature in the left leg and loss of conscious proprioception in the right leg. In addition, there will be damage to the descending corticospinal fibers that normally are essential for activation of the LMNs that control muscles of the right leg (i.e., UMN paralysis of the right leg). However, since the lesion is situated below the entry of sensory fibers as well as the origin of anterior horn cells that innervate the upper limbs, no loss of sensation to the upper limbs will ensue, nor will there be an LMN or UMN paralysis of the upper limbs. The pain and temperature fibers ipsilateral to the site of the lesion are unaffected because the second-order neurons decussate at the approximate level of their cell bodies of origin and ascend on the side contralateral to the lesion, leaving this system intact.

3. A 65-year-old man presents with increasing fatigue and shortness of breath. Examination of his peripheral blood finds pancytopenia, and a few (less than 5%) immature cells are present. Some of the neutrophils are bilobed (Pelger-Huët change) and a dimorphic red blood cell population is seen. A bone marrow biopsy reveals a hypercellular marrow with about 15% of the cells being immature cells. Approximately 20% of the red cell precursors have iron deposits that encircled the nucleus. Which of the following is the most likely cause of these clinical findings?

A. Chronic blood loss

B. Iron deficiency

C. Lead poisoning

D. Myelodysplasia

E. Vitamin B₁₂ deficiency

The answer is D.

EXPLANATION: The myelodysplastic syndromes (MDS) are a group of disorders characterized by defective hematopoietic maturation and an increased risk of developing acute leukemia. These disorders characteristically have hypercellular bone marrows but pancytopenia in the peripheral blood. The two basic types of MDS are an idiopathic (primary) form and a therapy-related (secondary) form. Both have numerous dysplastic features affecting all blood cell lines. Red cell dysplastic features include the presence of ringed sideroblasts, megaloblastoid erythroid precursors, and misshapen erythroid precursors. A dimorphic population of red cells may be seen in the peripheral blood of some patients with some types of MDS. White cell dysplastic features include hypogranular cells or Pelger-Huët white blood cells, which are abnormal appearing neutrophils having only two nuclear lobes. Megakaryocytes may be abnormal and have only a single nuclear lobe or multiple separate nuclei, so-called "pawn ball" megakaryocytes. Chromosomal abnormalities are commonly associated with the MDSs, especially 5q_ and trisomy 8.

Except for chronic myelomonocytic leukemia (CMML), which is characterized by a marked increase in the number of monocytes, the MDSs are subclassified by the number of blasts present within the bone marrow. The FAB classification of MDS is as follows: if there are less than 5% blasts present, the MDS is either refractory anemia (RA) or RA with ring sideroblasts (RARS). RA with excess blasts (RAEB, pronounced "rab") has between 5 and 20% blasts, while refractory anemia with excess blasts in transformation (RAEBIT, pronounced "rabbit") has between 20 and 30% blasts in the marrow. Acute leukemia is defined as the presence of more than 30% blasts in the marrow. The WHO (World Health Organization) has a similar classification of the MDS except that in their classification the number of blasts in the bone marrow needed for the diagnosis of acute leukemia is only 20%.

4. A hospital worker is found to have hepatitis B surface antigen. Subsequent tests reveal the presence of e antigen as well. Which of the following best describes the worker?

A. Is infective and has active hepatitis

B. Is infective but does not have active hepatitis

C. Is not infective

D. Is evincing a biologic false-positive test for hepatitis

E. Has both hepatitis B and hepatitis C

The answer is A.

EXPLANATION: The e antigen is related to the hepatitis B virus and is associated with viral replication (Dane particle). Possession of the e antigen suggests active disease and thus an increased risk of transmission of hepatitis to others. HBsAg and e antigen are components of hepatitis B only and are not shared by other hepatitis viruses.

5. A patient who has been taking an oral antihypertensive drug for about a year develops a positive Coombs' test. Which of the following drugs is the most likely cause?

A. Captopril

B. Clonidine

C. Labetalol

D. Methyldopa

E. Prazosin

The answer is D.

EXPLANATION: Among all the common oral antihypertensives, a Coombs-positive test is associated with methyldopa. It occurs in up to about 20% of patients taking this drug long term. Although rare, it may progress to hemolytic anemia. The cause is formation of a hapten on erythrocyte membranes, which induces an immune reaction (IgG antibodies) directed against and potentially lysing the red cell membrane. Other drugs with the potential to cause an immunohemolytic anemia are penicillins, quinidine, procainamide, and sulfonamides.

6. A 56-year-old man has heart failure. His family doctor, who has been caring for him since he was a young lad, has been treating him with digoxin, furosemide, and triamterene for several years. The patient now develops atrial fibrillation, and so his doctor starts quinidine and warfarin. Which of the following is the most likely outcome of adding the quinidine?

A. Development of signs and symptoms of quinidine toxicity (cinchonism)

B. Hyponatremia due to quinidine's ability to enhance diuretic-induced sodium loss

C. Onset of signs and symptoms of digoxin toxicity

D. Precipitous development of hypokalemia

E. Prompt suppression of cardiac contractility, onset of acute heart failure

The answer is C.

EXPLANATION: Digoxin toxicity is likely to occur within 24 to 48 h unless the digoxin dose is adjusted down. The reason is that quinidine will reduce the renal excretion of digoxin (digoxin's main elimination route). This is probably due to some mechanism by which quinidine inhibits P-glycoprotein transport of digoxin in the kidneys.

There is no "reverse interaction"—that is, an ability of digoxin to cause signs and symptoms of quinidine toxicity (a). Quinidine has no significant impact on the renal actions of any diuretics, whether these actions are expressed in terms of urine output (volume or concentration) or renal handling of sodium or potassium or other electrolytes or solutes (b, d).

Quinidine-induced digoxin toxicity may suppress cardiac contractility, but that would not be a direct effect of an interaction on the inotropic state of the myocardium. Rather, it would be secondary to potential digoxin-induced arrhythmias, and it would not occur "promptly."

Quinidine does cause some drug-drug interactions by pharmacokinetic mechanisms. It is a potent inhibitor of CYP2D6, and can, for example, inhibit the analgesic effects of codeine by inhibiting its metabolism to morphine. However, this mechanism does not apply to the quinidine-digoxin interaction; digoxin is eliminated completely by the kidneys, with no prior metabolism.

7. A 29-year-old woman complains of postprandial right upper quadrant pain and fatty food intolerance. Ultrasound examination reveals no evidence of gallstones or sludge. Upper endoscopy is normal, and all of her liver function tests are within normal limits. She then undergoes a CCK-HIDA scan, which reveals that her gallbladder ejection fraction is 15% at 20 minutes. Which of the following is true regarding her treatment options?

A. Avoidance of fatty foods is the only therapeutic option.

B. Ultrasound examination should be repeated immediately, since the false-negative rate for ultrasound in detecting gallstones is 10% to 15%.

C. Treatment with ursodeoxycholic acid results in improvement in symptoms in 35% of patients.

D. Laparoscopic cholecystectomy results in improvement in symptoms in 85% of patients.

E. Surgical intervention should be reserved for patients whose symptoms do not resolve with conservative treatment.

The answer is D.

EXPLANATION: Cholecystectomy results in improvement in symptoms in 85% to 94% of patients with biliary dyskinesia. The diagnosis is confirmed by CCK-HIDA scan. Technetium labeled hydroxy-iminodiacetic acid (HIDA) is injected intravenously, which is subsequently excreted into the biliary tract. After filling of the gallbladder, cholecystokinin (CCK), a hormone that is normally released by the duodenum after ingestion of a meal, is infused intravenously to stimulate gallbladder contraction. A gallbladder ejection fraction of less than 35% at 20 minutes is diagnostic of biliary dyskinesia. There is no role for oral dissolutional therapy with ursodeoxycholic acid in the treatment of biliary colic, since no gallstones are present.

8. A 32-year-old man with a 3-year history of ulcerative colitis (UC) presents for discussion for surgical intervention. Which of the following is true regarding total proctocolectomy for UC?

A. Patients with UC should consider surgery after 5 years because the risk of carcinoma increases to greater than 50%.

B. Symptoms relating to peripheral arthritis or ankylosing spondylitis will improve or resolve after proctocolectomy.

C. Early proctocolectomy can prevent the development of primary sclerosing cholangitis (PSC) in UC patients.

D. Proctocolectomy is not advised in younger patients because of the need for a permanent ileostomy.

E. Preservation of the rectum is a surgical option in the definitive management of UC.

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The answer is B.

EXPLANATION: Although total proctocolectomy may relieve or resolve extraintestinal manifestations of UC such as peripheral arthritis or ankylosing spondylitis, surgery is not preventative or curative for primary sclerosing cholangitis. The risk of colon cancer in pancolitis is 0% to 3% at 5 and 10 years and increases to 50% after 30 years with the disease. In patients with both PSC and UC, the risk of cancer is increased fivefold from that for patients with UC alone. Indications for operative intervention in UC include acute management of toxic megacolon or fulminant colitis and definitive management for intractable disease or presence of high-grade dysplasia or carcinoma. Definitive surgical management options for UC include total proctocolectomy with end ileostomy (typically reserved for older or incontinent patients) and total proctocolectomy with ileoanal pouch anastomosis. In patients undergoing emergent colectomy for toxic megacolon, total abdominal colectomy without resection of the rectum can be performed initially. However, given that UC always involves the rectum, definitive management of UC requires resection of most of the rectal mucosa, although controversy exists regarding retention of the very distal rectal mucosa such as with a stapled ileoanal anastomosis.

9. A mother brings her son in to see you. He is almost 2 years old, and had a significant amount of painless bleeding from his rectum last evening. He is currently hemodynamically stable, and in no distress when you see him. Which of the following is the most likely diagnosis?

A. Juvenile polyposis

B. Colitis

C. Anal fissure

D. Intussusception

E. Meckel diverticulum

The answer is E.

EXPLANATION: Meckel diverticulum is the most common cause of significant GI bleeding in children. It is a congenital abnormality that occurs in about 2% of the population, with a male to female ratio of 2 to 1. It occurs about 2 ft from the ileocecal valve, and is usually about 2 in long. About 2% of cases have complications. These facts are often remembered as "the rule of 2s." Intussusception also occurs in this age group, but is usually painful. Anal fissures, colitis, and juvenile polyposis generally do not cause significant bleeding.

10. One of your patients is dying of end-stage breast cancer. She is complaining of dyspnea. Which of the following treatment options would be most beneficial?

A. Bronchodilators

B. Steroids

C. Anxiolytics

D. Opioids

E. Pulmonary rehabilitation program

The answer is D.

EXPLANATION: Many studies have shown that opioids relieve dyspnea in patients with cancer, but the mechanism is unknown. Bronchodilators are better in the setting of COPD and asthma, as are steroids. Anxiolytics help, but seem to relieve the anxiety associated with dyspnea more than the dyspnea itself. Pulmonary rehabilitation would be an inappropriate step in a dying patient.

11. You are evaluating a 47-year-old woman complaining of bilateral lower extremity edema. She denies dyspnea, and on examination has no rales, JVD, or ascites. Her cardiac examination is normal. What should be the next step in the evaluation of her edema?

A. Echocardiogram

B. Thyroid-stimulating hormone (TSH) assessment

C. Liver function studies

D. Lower extremity Doppler

E. Urinalysis

The answer is E.

EXPLANATION: In the workup of edema, the first thing to note is if the edema is bilateral or unilateral. Bilateral edema associated with signs and symptoms of CHF (dyspnea, rales, or JVD) would necessitate a chest x-ray to rule in the diagnosis, followed by an echocardiogram. If ascites is present, liver function studies are needed. If these are absent, the clinician should check an urinalysis. If the sediment is abnormal, nephritic syndrome or acute tubular necrosis (ATN) is the likely diagnosis.

12. A 33-year-old woman at 10 weeks presents for her first prenatal examination. Routine labs are drawn and her hepatitis B surface antigen is positive. Liver function tests are normal and her hepatitis B core and surface antibody tests are negative. Which of the following is the best way to prevent neonatal infection?

A. Provide immune globulin to the mother.

B. Provide hepatitis B vaccine to the mother.

C. Perform a cesarean delivery at term.

D. Provide hepatitis B vaccine to the neonate.

E. Provide immune globulin and the hepatitis B vaccine to the neonate.

The answer is E.

EXPLANATION: Infection of the newborn whose mother chronically carries the hepatitis B virus can usually be prevented by the administration of hepatitis B immune globulin very soon after birth, followed promptly by the hepatitis B vaccine.

13. A 71-year-old woman is diagnosed with small-cell lung cancer. Which of the following statements regarding small-cell lung carcinoma is true?

A. It represents about 80% of all lung cancers.

B. Most are located peripherally.

C. It rarely spreads to mediastinal lymph nodes.

D. It is slow growing and rarely metastasizes.

E. Most are treated with chemotherapy and radiation instead of surgery.

The answer is E.

EXPLANATION: Small cell lung cancers are treated primarily with chemotherapy and radiation; they are rarely amenable to surgical resection because of extensive disease at presentation. Small cell lung cancer accounts for about 20% of primary lung cancers. Most are centrally located and characterized by an aggressive tendency to metastasize. They spread early to mediastinal lymph nodes and distant sites, most commonly to the bone marrow and the brain.

14. A 65-year-old woman is brought into the ED by her family who states that she has been weak, lethargic, and saying "crazy things" over the last 2 days. Her family also states that her medical history is significant only for a disease of her thyroid. Her BP is 120/90 mm Hg, HR is 51 beats per minute, temperature is 94°F rectally, and her RR is 12 breaths per minute. On examination, the patient is overweight, her skin is dry, and you notice periorbital nonpitting edema. On neurologic examination, the patient does not respond to stimulation. Which of the following is the most likely diagnosis?

A. Apathetic thyrotoxicosis

B. Myxedema coma

C. Graves disease

D. Acute stroke

E. Schizophrenia

The answer is B.

EXPLANATION: Myxedema coma is a syndrome that represents extreme hypothyroidism. It is a life-threatening condition that has a mortality of up to 50%. Signs and symptoms of hypothyroidism are usually present including dry skin, delayed deep tendon reflexes, coarse hair, and generalized nonpitting edema. Myxedema coma, however, is better characterized by profound lethargy or coma and hypothermia. Hypothermia is present in approximately 80% of patients. In addition, patients may present with respiratory depression and sinus bradycardia.

(a) Apathetic thyrotoxicosis is an atypical presentation of hyperthyroidism seen commonly in the elderly but noted in all ages. Signs and symptoms are few and subtle. Patients usually have multinodular goiter. The diagnosis should be considered in elderly patients with chronic weight loss, proximal muscle weakness, depressed affect, new-onset atrial fibrillation, or congestive heart failure. (c) Graves disease is secondary to autoimmune stimulation of thyrotropin (TSH) receptors leading to elevated levels of thyroid hormones. (d) An acute stroke should not cause periorbital edema and hypothermia. (e) Schizophrenia may be mistakenly diagnosed in patients with thyroid abnormalities. It is not a correct diagnosis in this scenario when the patient is unconscious and hypothermic.

15. A 21-year-old, right-handed female student was working in the photography lab 1 week ago, which required standing all day. After that, she experienced a cold sensation in the left foot and her entire left leg fell asleep. The feeling lasted 4 to 5 days and then slowly went away. Her right lower extremity was fine. Coughing, sneezing, and the Valsalva maneuver did not worsen her symptoms. She had a slight back pain, which she thought was due to using a poor mattress. Past history includes an episode of optic neuritis in the left eye 2 years ago. At that time, she was reportedly depressed and was sleeping constantly. One day, her left eye became blurred and her vision went out. In 1 week, her vision returned to normal. Her vision now is 20/20. She has not had a repeat episode since then. She had an MRI of her brain, which was normal at that time. She drinks alcohol occasionally and does not use any illicit drugs. Her only medication is birth control pills. Examination is significant for brisk reflexes and sustained clonus at the right ankle. Babinski sign is present on the right. Testing is positive for oligoclonal bands. Which of the following is the most likely diagnosis in this case?

A. Seizure

B. Transient ischemic attack

C. Anaplastic astrocytoma

D. Multiple sclerosis (MS)

E. Parkinson disease

The answer is D.

EXPLANATION: This is a typical history for multiple sclerosis (MS). Multiple sclerosis is a progressive demyelinating disease of the central nervous system. Risk factors include a first-time demyelinating episode such as optic neuritis. Patients are more commonly in the 20 to 30 age range, with a higher incidence in women. A transient ischemic attack is a brief period of brain ischemia causing neurological deficits that resolve within 24 hours. Patients who have a transient ischemic attack are at increased risk for stroke. A seizure is abnormal rhythmic electrical brain activity with a clinical correlation. There is nothing in the history to suggest that this patient had a seizure or a seizure predisposing factor. Seizure predisposing factors include previous seizure, brain trauma, brain hemorrhage, and encephalitis. An anaplastic astrocytoma is a malignant high-grade brain tumor. These often present with a seizure or hemorrhage. Risk factors include previous brain tumor. Parkinson disease is caused by a loss of dopaminergic neurons. It is characterized by asymmetric slowness, rigidity, and tremor. Risk factors include family history.

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