Question 1: Two hours after vaginal delivery at term of a 3062-g (6-lb 12-oz) newborn, a 32-year-old woman, gravida 3, para 3, has the onset of heavy vaginal bleeding. Labor was augmented with oxytocin because of a prolonged first stage and required forceps delivery over a midline second-degree episiotomy. The abdomen is soft and nontender. Examination shows a boggy uterus palpated 4 cm above the umbilicus. The perineum is intact. Which of the following is the most likely cause of this patient’s hemorrhage?

• Disseminated intravascular coagulation
• Uterine atony (Correct answer)
• Uterine infection
• Episiotomy site bleeding
• Uterine rupture

Correct answer: Uterine atony

The most common cause of postpartum hemorrhage is uterine atony, which is characterized by a boggy, enlarged uterus that fails to contract after delivery. Risk factors present in this patient include prolonged labor and oxytocin augmentation. The intact perineum rules out significant lacerations, and the boggy uterus strongly points to atony as the cause of the heavy bleeding.

Question 2: A 7-year-old boy fails to develop spoken language, avoids eye contact, and engages in repetitive rocking movements. He was hitting all developmental milestones until age 18 months. What is the most likely diagnosis?

• Fragile X syndrome
• Autism spectrum disorder (Correct answer)
• Rett syndrome
• Selective mutism

Correct answer: Autism spectrum disorder

Autism spectrum disorder presents with deficits in social communication and restricted/repetitive behaviors; early development may appear normal before regression.

Question 3: A patient on loop diuretics for heart failure develops muscle cramps and weakness. Which electrolyte abnormality most likely explains these symptoms?

• Hypernatremia
• Hypokalemia (Correct answer)
• Hypermagnesemia
• Hyperchloremia

Correct answer: Hypokalemia

Loop diuretics inhibit the Na-K-2Cl transporter in the thick ascending limb, causing urinary potassium wasting and hypokalemia, which leads to muscle dysfunction.

Question 4: A 60-year-old woman comes to the physician because she recently was diagnosed with non-small cell lung carcinoma and she wants to discuss possible treatment options. She tells the physician that she is concerned about the possible adverse effects of chemotherapy. The physician says that serious toxicity caused by antineoplastic drugs is seen in the bone marrow. Which of the following best explains this finding?

• Cells in the marrow divide rapidly (Correct answer)
• Chemotherapy drugs tend to be lipid-soluble and concentrate in the marrow
• Cells in the marrow lack the enzymes to protect against the drugs
• Chemotherapy drugs penetrate well into the marrow because it is very vascular
• Chemotherapy drugs act preferentially against cells with no nucleus
• Cells in the marrow have specific surface targets for most of these drugs

Correct answer: Cells in the marrow divide rapidly

Antineoplastic drugs, especially conventional chemotherapy agents, primarily target rapidly dividing cells. Bone marrow cells, including hematopoietic stem cells and their precursors, are among the most rapidly proliferating cells in the body. This high rate of cell division makes them particularly susceptible to the cytotoxic effects of chemotherapy, leading to common adverse effects like myelosuppression.

Question 5: An autopsy of a 68-year-old man with dementia shows senile plaques and neurofibrillary tangles. Which protein forms the core of senile plaques?

• Tau protein
• Amyloid-beta (Abeta42) (Correct answer)
• TDP-43
• Alpha-synuclein

Correct answer: Amyloid-beta (Abeta42)

Senile (neuritic) plaques in Alzheimer disease are composed of extracellular amyloid-beta peptide (predominantly Abeta42) derived from APP cleavage.

Question 6: A 32-year-old man comes to the physician because of a 12-day history of abdominal cramps and bloating, diarrhea, and flatulence. He says that he started a new exercise program 2 weeks ago and has been consuming a high quantity of yogurt bars, peanut butter, and protein- and calorie-enriched milk shakes to “bulk up.” He has no history of serious illness and takes no medications. His temperature is 37°C (98.6°F). The abdomen is distended, nontender, and tympanitic to percussion. Bowel sounds are increased. The remainder of the examination shows no abnormalities. Which of the following is the most likely cause of this patient’s symptoms?

• Allergy to peanuts
• Irritable bowel syndrome
• Fungal overgrowth in the small bowel
• Incarcerated hernia
• Lactase deficiency (Correct answer)

Correct answer: Lactase deficiency

The patient's symptoms of abdominal cramps, bloating, diarrhea, and flatulence, which began after increasing his consumption of dairy-containing products like yogurt bars and milkshakes, are highly suggestive of lactase deficiency (lactose intolerance). This condition results from the inability to digest lactose, leading to its fermentation by gut bacteria and the production of gas and osmotic diarrhea.

Question 7: A 72-year-old nursing home resident presents with fever, productive cough, and right lower lobe consolidation on CXR. He has dysphagia. Which organism is most likely responsible?

• Streptococcus pneumoniae
• Aspiration of oral flora (polymicrobial) (Correct answer)
• Pseudomonas aeruginosa
• Legionella pneumophila

Correct answer: Aspiration of oral flora (polymicrobial)

Aspiration pneumonia in a dysphagic nursing home patient is typically polymicrobial, involving oral anaerobes and gram-negative organisms.

Question 8: A 4-year-old boy is brought to the physician by his parents because of a 4-month history of difficulty running and frequent falls. His parents report that his calves have been gradually increasing in size during this period. Examination shows diffusely enlarged muscles of the calves and lumbar lordosis. Sensation is intact. He has difficulty arising from a supine position. Which of the following is the most likely diagnosis?

• Juvenile idiopathic arthritis
• Spina bifida
• Duchenne muscular dystrophy (Correct answer)
• Rhabdomyosarcoma
• Lumbosacral radiculopathy

Correct answer: Duchenne muscular dystrophy

This presentation is highly characteristic of Duchenne muscular dystrophy (DMD), an X-linked recessive neuromuscular disorder. Key features include progressive proximal muscle weakness (leading to difficulty running and frequent falls), pseudohypertrophy of the calves (due to muscle tissue being replaced by fat and fibrous tissue), and Gowers' sign (difficulty rising from a supine position). The intact sensation helps differentiate it from neurological conditions.

Question 9: A 40-year-old woman with systemic lupus erythematosus has a kidney biopsy showing 'wire loop' lesions. What is deposited in these capillary walls?

• IgA deposits
• Anti-GBM antibodies
• IgG and C3 immune complexes (Correct answer)
• Amyloid fibrils

Correct answer: IgG and C3 immune complexes

Wire loop lesions in lupus nephritis (class IV) represent subendothelial immune complex deposits causing marked capillary wall thickening.

Question 10: A 21-year-old college student comes to student health services requesting medication to help her sleep. Four days ago, she returned from a 1-year trip to India where she studied comparative religions. Since her return, she has been unable to fall asleep until 4 or 5 AM and has difficulty awakening before noon. She constantly feels tired, has difficulty concentrating, and does not feel ready to begin classes. Her appetite has not decreased, but she has an aversion to eating meat since following a vegetarian diet in India. She has no history of medical or psychiatric illness. She takes no medications and does not drink alcohol. She appears sleepy. She is 173 cm (5 ft 8 in) tall and weighs 54 kg (120 lb); BMI is 18 kg/m2 . Her pulse is 60/min, and blood pressure is 115/70 mm Hg. She is alert and oriented to person, place, and time. When asked to subtract serial sevens from 100, she begins accurately but then repeatedly loses track of the sequence. Which of the following is the most likely diagnosis?

• Malingering
• Primary insomnia
• Major depressive disorder
• Bipolar disorder
• Adjustment disorder with depressed mood
• Circadian rhythm sleep disorder (Correct answer)

Correct answer: Circadian rhythm sleep disorder

The patient's symptoms of difficulty falling asleep and waking, coupled with fatigue and impaired concentration, immediately following a long-distance international trip (India to presumably a Western country, implying significant time zone change), are classic for a circadian rhythm sleep disorder, specifically jet lag disorder. Her internal biological clock is still aligned with the previous time zone, causing a mismatch with the local day-night cycle.

Question 11: A clinical trial of a potentially valuable medical treatment is planned. It is unlikely that it will directly benefit the study subjects but very likely that it will benefit future patients. There is a risk for short-term minor gastric discomfort but essentially no risk for long-term adverse effects. The investigator concludes that disclosure of the risks may discourage participation in the trial. Which of the following is the most appropriate next step?

• Proceed with the trial without disclosure, because the probability of long-term harm to subjects is remote
• Proceed with the trial only with disclosure, because the trial will not directly benefit the subjects
• Proceed with the trial using only subjects who agree to participate without disclosure
• Proceed with the trial without disclosure, because the risks to subjects are outweighed by the possible benefits to many patients
• Proceed with the trial only with disclosure, because informed consent is an absolute requirement (Correct answer)

Correct answer: Proceed with the trial only with disclosure, because informed consent is an absolute requirement

The ethical principle of informed consent mandates that all potential risks, benefits, and alternatives of a research study must be fully disclosed to prospective participants. Even if the risks are minor and the treatment is potentially valuable, withholding information compromises the autonomy of the subjects and is unethical. Informed consent is an absolute requirement to ensure participants can make a voluntary and educated decision about their involvement in the trial.

Question 12: A 65-year-old man has had increasingly severe headaches and diffuse muscle aches during the past 3 months. He also has a 1-month history of jaw pain when chewing food and decreasing visual acuity in his left eye. His temperature is 38°C (100.4°F). Visual acuity in his left eye is 20/100, and the left optic disc is slightly atrophic. His muscle strength is normal. Which of the following tests should be obtained next?

• Measurement of erythrocyte sedimentation rate (Correct answer)
• Examination of cerebrospinal fluid
• Antinuclear antibody assay
• Electroencephalography
• CT scan of the head

Correct answer: Measurement of erythrocyte sedimentation rate

This patient's age, new-onset headaches, diffuse muscle aches (polymyalgia rheumatica-like symptoms), jaw pain when chewing (jaw claudication), and acute monocular vision loss are classic symptoms of giant cell (temporal) arteritis. This condition is a medical emergency due to the risk of permanent blindness. The most crucial initial diagnostic test is the erythrocyte sedimentation rate (ESR), which is almost always markedly elevated in active giant cell arteritis and guides immediate treatment with corticosteroids.

Question 13: A 58-year-old woman undergoes a mastectomy. Histology shows invasive carcinoma with Indian file (single-file) growth pattern and absence of cohesion due to loss of which protein?

• E-cadherin (Correct answer)
• Vinculin
• ERM proteins
• Beta-catenin

Correct answer: E-cadherin

Invasive lobular carcinoma is characterized by single-file tumor cells due to loss of E-cadherin expression from CDH1 mutation or promoter methylation.

Question 14: A 43-year-old man sustains a wound to the lateral neck. This results in weakness of elevation and retraction of the shoulder on the ipsilateral side and difficulty turning the head up and toward the contralateral side. No sensory changes are present. Which of the following nerves most likely has been injured?

• Spinal accessory (Correct answer)
• Suprascapular
• Axillary
• Phrenic
• Lateral cord of the brachial plexus

Correct answer: Spinal accessory

The spinal accessory nerve (cranial nerve XI) is a pure motor nerve that innervates the sternocleidomastoid and trapezius muscles. Injury to this nerve would cause weakness in elevating and retracting the ipsilateral shoulder (trapezius) and difficulty turning the head up and toward the contralateral side (sternocleidomastoid). The absence of sensory changes is consistent with a pure motor nerve injury. The other nerves listed have different motor or sensory distributions.

Question 15: A 32-year-old woman undergoing IVF achieves a positive β-hCG two weeks after embryo transfer. She presents with severe abdominal distension, dyspnea, and 6 kg weight gain over 5 days. What is the most likely diagnosis?

• Ovarian hyperstimulation syndrome (OHSS) (Correct answer)
• Heterotopic pregnancy
• Ovarian torsion
• Ruptured ectopic pregnancy

Correct answer: Ovarian hyperstimulation syndrome (OHSS)

OHSS is a complication of ovarian stimulation characterized by massive fluid shifts, ascites, weight gain, and dyspnea, worsened by the rise in hCG from an established pregnancy.

Question 16: An 83-year-old man has a 2-month history of akinesia, rigidity, and tremor. He has been taking a drug for the past 7 years to control severe behavioral and psychiatric symptoms associated with dementia, Alzheimer type. This adverse effect is most likely mediated through which of the following?

• Antidopaminergic effects (Correct answer)
• Inhibition of serotonin reuptak
• Downregulation of γ-aminobutyric acid (GABA)
• Inhibition of norepinephrine reuptake
• Upregulation of GABA
• Anticholinergic effects

Correct answer: Antidopaminergic effects

The patient's symptoms of akinesia, rigidity, and tremor are characteristic of drug-induced parkinsonism, also known as extrapyramidal symptoms. These adverse effects commonly occur with antipsychotic medications, which are often used for behavioral symptoms in dementia. Antipsychotics exert their effects by blocking dopamine D2 receptors in the brain, leading to an imbalance in the basal ganglia that mimics Parkinson's disease.

Question 17: A 36-year-old woman with hypertension well-controlled on lisinopril asks about contraception. Which method is CONTRAINDICATED in this patient?

• Copper intrauterine device
• Levonorgestrel-releasing IUD
• Combined estrogen-progestin oral contraceptives (Correct answer)
• Progestin-only pills (mini-pill)

Correct answer: Combined estrogen-progestin oral contraceptives

Combined oral contraceptives are contraindicated in women with hypertension due to increased risk of stroke and myocardial infarction, especially over age 35.

Question 18: An elderly nursing home resident develops watery diarrhea after a prolonged course of clindamycin. Stool toxin assay is positive. The pathogen produces two toxins: Toxin A (enterotoxin) and Toxin B (cytotoxin). Which treatment is first-line for a non-severe initial episode?

• Oral rifaximin
• Oral metronidazole
• Oral vancomycin or fidaxomicin (Correct answer)
• Intravenous metronidazole

Correct answer: Oral vancomycin or fidaxomicin

Current IDSA guidelines recommend oral vancomycin or fidaxomicin as first-line therapy for initial non-severe Clostridioides difficile infection; fidaxomicin has lower recurrence rates.

Question 19: A 68-year-old man with hypertension suddenly develops left-sided weakness and facial droop. Symptoms began 2 hours ago. CT head shows no hemorrhage. NIHSS is 8. What is the most appropriate next step?

• Heparin infusion
• IV tPA (alteplase) administration (Correct answer)
• Aspirin 325 mg immediately
• CT angiography followed by observation

Correct answer: IV tPA (alteplase) administration

IV tPA is indicated for ischemic stroke within 4.5 hours of symptom onset in eligible patients with no contraindications, and is the most appropriate acute treatment here.

Question 20: A 6-year-old with sickle cell disease presents with sudden onset of severe abdominal pain, splenomegaly, pallor, and a hemoglobin drop from 9 to 4 g/dL. Diagnosis?

• Aplastic crisis
• Vaso-occlusive crisis
• Acute chest syndrome
• Acute splenic sequestration (Correct answer)

Correct answer: Acute splenic sequestration

Acute splenic sequestration in sickle cell disease causes sudden trapping of blood in the spleen, producing rapid anemia and splenomegaly.

Question 21: A 4-year-old boy squeals and cries but uses no words. His gross and fine motor skills are well developed. He is preoccupied with objects and does not play with other children. The child responds normally to sounds but appears disinterested and detached. For each child brought for a well-child examination, select the most likely diagnosis

• Neurodegenerative disorder
• Ankyloglossia (tongue-tie)
• Hearing loss
• Selective mutism
• Attention-deficit/hyperactivity disorder
• Normal language development
• Serous otitis media
• Mental retardation
• Parental neglect
• Autistic disorder (Correct answer)

Correct answer: Autistic disorder

This 4-year-old boy exhibits significant delays in verbal communication (no words, only squeals and cries), impaired social interaction (does not play with other children, disinterested and detached), and restricted, repetitive behaviors (preoccupation with objects). These core deficits in social communication and interaction, along with restricted and repetitive patterns of behavior, are the hallmark diagnostic criteria for autistic disorder.

Question 22: A patient is receiving heparin for a DVT. Her platelet count drops from 250,000 to 60,000 after 8 days of therapy. Which drug should be used to continue anticoagulation?

• Low molecular weight heparin
• Argatroban (Correct answer)
• Aspirin
• Warfarin

Correct answer: Argatroban

Heparin-induced thrombocytopenia (HIT) requires immediate discontinuation of all heparin products and substitution with a direct thrombin inhibitor such as argatroban.

Question 23: A clinical isolate of Staphylococcus aureus is resistant to all beta-lactam antibiotics, including extended-spectrum penicillins and carbapenems. Which mechanism is responsible?

• Efflux pump overexpression
• Production of a broad-spectrum beta-lactamase
• Acquisition of mecA gene encoding an altered penicillin-binding protein (PBP2a) (Correct answer)
• Decreased outer membrane permeability

Correct answer: Acquisition of mecA gene encoding an altered penicillin-binding protein (PBP2a)

MRSA acquires the mecA gene (carried on SCCmec) encoding PBP2a, which has very low affinity for all beta-lactam antibiotics, conferring pan-beta-lactam resistance.

Question 24: A 16-month-old boy is brought to the physician by his mother for a well-child examination. His mother expresses concern that he did not walk until the age of 14 months, whereas his older sister walked at the age of 10 months. Physical examination shows no abnormalities. Which of the following best explains this patient’s condition?

• Child abuse
• Oppositional defiant disorder
• Autistic disorder
• Normal development (Correct answer)
• Sensory integration disorder

Correct answer: Normal development

The normal range for independent walking is typically between 9 and 18 months of age. Walking at 14 months falls well within this normal developmental window. While his older sister walked earlier, individual variations in developmental milestones are common and do not indicate a problem unless they fall outside established normal ranges or are accompanied by other concerning signs.

Question 25: A 62-year-old man is being treated with cisplatin for small cell carcinoma of the lungs. The efficacy of cisplatin depends on interaction with which of the following?

• Reverse transcriptase
• Growth factor receptors
• DNA (Correct answer)
• DNA polymerase
• Ribosomes

Correct answer: DNA

Cisplatin is a platinum-based antineoplastic agent used in chemotherapy. Its efficacy stems from its ability to form highly reactive platinum complexes that bind to and cross-link DNA strands within cancer cells. This DNA damage inhibits DNA replication and transcription, ultimately leading to apoptosis of rapidly dividing tumor cells, making it effective against small cell carcinoma of the lungs.

Question 26: A 21-year-old woman comes to the physician for counseling prior to conception. She delivered a female newborn with anencephaly 1 year ago. The newborn died at the age of 4 days. She asks the physician if she can take any vitamins to decrease her risk for conceiving a fetus with anencephaly. It is most appropriate for the physician to recommend which of the following vitamins?

• Vitamin B6 (pyridoxine)
• Biotin
• Vitamin B1 (thiamine)
• Vitamin B12 (cyanocobalamin)
• Vitamin B2 (riboflavin)
• Folic acid (Correct answer)

Correct answer: Folic acid

Anencephaly is a severe neural tube defect (NTD) that occurs during early fetal development. Supplementation with folic acid (vitamin B9) before conception and during the first trimester of pregnancy has been extensively proven to significantly reduce the risk of NTDs. Folic acid is crucial for DNA synthesis and repair, and for cell division, which are vital processes during neural tube closure.

Question 27: A previously healthy 4-year-old boy is brought to the emergency department 8 hours after the onset of fever and a diffuse, constant headache. He had been well until 2 days ago when he developed malaise. Yesterday, he slept more than usual and had temperatures to 39.2°C (102.5°F). Immunizations are up-to-date. He is lethargic and irritable when aroused. He holds his head extended and cries when his neck is flexed. Muscle strength is normal, and deep tendon reflexes are symmetrically increased. A lumbar puncture yields turbid cerebrospinal fluid. Laboratory studies show: Serum glucose 120 mg/dL Cerebrospinal fluid Opening pressure 250 mm H2O Glucose 10 mg/dL Protein 85 mg/dL Leukocyte count 750/mm3 Segmented neutrophils 95% Lymphocytes 5% Erythrocyte count 0/mm3 A Gram stain of cerebrospinal fluid shows gram-negative diplococci. A CT scan of the head shows no abnormalities. Which of the following is the most likely causal organism?

• Varicella-zoster virus
• Neisseria meningitidis (Correct answer)
• Cytomegalovirus
• Haemophilus influenzae
• Streptococcus agalactiae (group B)

Correct answer: Neisseria meningitidis

The patient's clinical presentation (fever, headache, lethargy, nuchal rigidity) combined with the cerebrospinal fluid (CSF) findings (turbid, high opening pressure, low glucose, high protein, high leukocyte count with neutrophil predominance) is characteristic of bacterial meningitis. The Gram stain showing gram-negative diplococci specifically identifies *Neisseria meningitidis* as the most likely causal organism in this age group.

Question 28: Type I error (α) in hypothesis testing is defined as:

• Using an inappropriately small sample size
• Having insufficient power to detect a true effect
• Rejecting a true null hypothesis (Correct answer)
• Failing to reject a false null hypothesis

Correct answer: Rejecting a true null hypothesis

A Type I error (false positive) occurs when the null hypothesis is actually true but is incorrectly rejected; its probability equals α.

Question 29: A 4-year-old boy is brought to the physician by his parents because of a 2-month history of difficulty sleeping. His parents report that he typically awakens 1 hour after going to sleep and cries loudly. When his parents come to his room, he appears frightened and is unaware of their attempts to comfort him. In the morning, he has no memory of these episodes. Physical examination shows no abnormalities. Which of the following is the most likely diagnosis?

• Seizure disorder
• Oppositional defiant disorder
• Factitious disorder
• Separation anxiety disorder
• Sleep terror disorder (Correct answer)

Correct answer: Sleep terror disorder

This 4-year-old boy's episodes of awakening from sleep with loud crying, appearing frightened, being unresponsive to parental comfort, and having no memory of the event in the morning, are classic features of sleep terror disorder. These episodes typically occur during non-REM sleep (early in the night) and are distinct from nightmares, which occur during REM sleep and are usually remembered.

Question 30: A 42-year-old woman comes to the physician for a follow-up examination after two separate Pap smears have shown dysplastic epithelial cells. Results of a molecular diagnostic test show DNA that encodes high-risk versions of the human papillomavirus E6 and E7 proteins. The viral E6 protein binds to the cellular p53 tumor suppressor gene, causing it to be degraded. Which of the following best describes the mechanism by which the E6 protein causes cervical cancer?

• Enhances tissue invasion and metastasis
• Sustains angiogenesis
• Inhibits telomerase expression
• Prevents apoptosis (Correct answer)
• Arrests the cell cycle

Correct answer: Prevents apoptosis

The p53 tumor suppressor protein is a critical regulator of the cell cycle and apoptosis. When DNA damage or cellular stress occurs, p53 can halt the cell cycle for repair or induce apoptosis if the damage is irreparable. By causing the degradation of p53, the HPV E6 protein removes this crucial checkpoint and pro-apoptotic signal, allowing damaged cells to continue proliferating and avoiding programmed cell death, thereby contributing to oncogenesis and cervical cancer development.

Question 31: A 22-year-old college student develops fever, pharyngitis, and posterior cervical lymphadenopathy. A peripheral blood smear shows atypical lymphocytes. The heterophile antibody test is positive. Which cell type is the primary reservoir for the causative virus?

• Epithelial cells
• T lymphocytes
• Monocytes
• B lymphocytes (Correct answer)

Correct answer: B lymphocytes

Epstein-Barr virus (EBV) infects B lymphocytes via CD21 (complement receptor 2); the atypical lymphocytes seen on smear are reactive cytotoxic T cells responding to infected B cells.

Question 32: A 3-year-old child has leukocoria (white pupillary reflex). Retinal biopsy shows small round cells with Flexner-Wintersteiner rosettes. What is the molecular mechanism?

• MYCN amplification
• Biallelic loss of the RB1 tumor suppressor gene (Correct answer)
• t(2;13) PAX3-FOXO1 fusion
• TP53 mutation

Correct answer: Biallelic loss of the RB1 tumor suppressor gene

Retinoblastoma results from biallelic inactivation of the RB1 gene (chromosome 13q14), which encodes pRb, the key regulator of the G1/S cell-cycle checkpoint.

Question 33: A 20-year-old African American woman comes to the physician because of a 6-month history of diffuse joint pain, especially in her hips and knees. During this period, she occasionally has had a rash on her nose and cheeks. She has no history of serious illness and takes no medications. Her temperature is 38.1°C (100.5°F). Examination shows warmth and swelling of the knees. Laboratory studies show: Hemoglobin 10.5 g/dL Erythrocyte sedimentation rate 40 mm/h Serum Urea nitrogen 30 mg/dL Creatinine 1.8 mg/dL Which of the following is the most likely diagnosis?

• Rheumatoid arthritis
• Systemic lupus erythematosus (Correct answer)
• Ankylosing spondylitis
• Reactive arthritis
• Gouty arthritis
• Septic arthritis
• Psoriatic arthritis

Correct answer: Systemic lupus erythematosus

This patient's constellation of symptoms, including diffuse joint pain (polyarthralgia/arthritis), a malar rash (rash on nose and cheeks), fever, anemia, elevated erythrocyte sedimentation rate (ESR), and evidence of renal involvement (elevated BUN and creatinine), is highly characteristic of systemic lupus erythematosus (SLE). SLE is a chronic autoimmune disease that can affect multiple organ systems.

Question 34: A 26-year-old woman presents with sudden paralysis of her right arm. Neurological exam reveals non-anatomic sensory loss. MRI is normal. She appears unconcerned ('la belle indifférence'). What is the most likely diagnosis?

• Conversion disorder (Correct answer)
• Factitious disorder
• Somatic symptom disorder
• Illness anxiety disorder

Correct answer: Conversion disorder

Conversion disorder (functional neurological symptom disorder) presents with neurological deficits inconsistent with anatomy, often with la belle indifférence, after a psychological stressor.

Question 35: A patient presents with hypocalcemia and spontaneous muscle tetany. Deficiency of which hormone is most likely responsible?

• Calcitonin
• Aldosterone
• Parathyroid hormone (PTH) (Correct answer)
• Cortisol

Correct answer: Parathyroid hormone (PTH)

PTH deficiency (hypoparathyroidism) reduces calcium reabsorption from bone and kidney, causing hypocalcemia and neuromuscular excitability.

Question 36: In the urea cycle, one nitrogen is derived from free ammonia and the other is donated by which compound?

• Glycine
• Glutamine
• Alanine
• Aspartate (Correct answer)

Correct answer: Aspartate

The two urea nitrogens originate from ammonium (via carbamoyl phosphate synthetase I) and from aspartate (incorporated at the argininosuccinate synthetase step).

Question 37: An asymptomatic 24-year-old primigravid woman at 36 weeks’ gestation comes for a routine prenatal visit. A grade 2/6, systolic ejection murmur is heard at the upper left sternal border. The S2 varies with inspiration, and the pulmonic component is soft; diastole is clear. Which of the following is the most likely diagnosis?

• Flow murmur (Correct answer)
• Anomalous pulmonary venous return
• Atrial septal defect
• Pulmonary valve stenosis
• Patent ductus arteriosus

Correct answer: Flow murmur

During pregnancy, increased blood volume and cardiac output lead to a hyperdynamic circulatory state. This often results in a physiologic 'flow murmur,' typically a systolic ejection murmur heard at the left sternal border, which is usually grade 1-2/6 and not associated with other signs of cardiac disease. The varying S2 with inspiration and soft pulmonic component are also consistent with normal physiological changes in pregnancy.

Question 38: A previously healthy 77-year-old woman who resides in a skilled nursing care facility is brought to the emergency department 6 hours after the onset of acute midback pain that began while lifting a box. The pain does not radiate, and she has no other symptoms. She continues to carry out her daily activities. She appears to be in mild distress. She is 157 cm (5 ft 2 in) tall and weighs 47 kg (104 lb); BMI is 19 kg/m2 . Examination shows mild tenderness over T11. There is no tremor. Serum studies show a calcium concentration of 9.1 mg/dL, a urea nitrogen concentration of 12 mg/dL, and a creatinine concentration of 0.5 mg/dL. An x-ray of the dorsal and lumbar spine shows an anterior wedge fracture of T11. In addition to treating the pain, supplementation with which of the following is most likely to improve this patient’s underlying condition?

• Selenium
• 25-Hydroxycholecalciferol (Correct answer)
• Vitamin C
• Levothyroxine
• Vitamin E

Correct answer: 25-Hydroxycholecalciferol

This elderly, frail woman (BMI 19) experienced an acute vertebral wedge fracture after minimal trauma (lifting a box), which is a classic fragility fracture indicative of osteoporosis. While pain management is important, addressing the underlying bone weakness is crucial. Supplementation with 25-hydroxycholecalciferol (Vitamin D) is essential for calcium absorption and bone mineralization, making it a cornerstone of osteoporosis treatment and prevention, especially in the elderly who are often deficient.

Question 39: A 32-year-old woman is brought to the emergency department because of fever, hallucinations, agitation, and confusion for 8 hours. She has a history of alcohol, cocaine, and benzodiazepine abuse. Her temperature is 37.8°C (100°F), pulse is 110/min, respirations are 16/min, and blood pressure is 150/90 mm Hg. Examination shows tremors and telangiectasia. The lungs are clear to auscultation. There is a holosystolic murmur; the abdomen is tender, and the liver edge is palpable 3 cm below the right costal margin. Rectal examination shows no abnormalities. Her serum alkaline phosphatase activity is 200 U/L, serum ALT activity is 60 U/L, and serum AST activity is 90 U/L. Which of the following is the most likely cause of this condition?

• Panic disorder
• Acute cocaine toxicity
• Alcohol withdrawal (Correct answer)
• Benzodiazepine withdrawal
• Schizophreniform disorder

Correct answer: Alcohol withdrawal

The patient's history of chronic alcohol abuse, combined with the acute onset of delirium (hallucinations, agitation, confusion), autonomic hyperactivity (tachycardia, hypertension, fever, tremors), and signs of chronic liver disease (telangiectasia, hepatomegaly, elevated AST/ALT ratio), strongly points to alcohol withdrawal, specifically delirium tremens. The symptoms are consistent with the severe end of the alcohol withdrawal spectrum.

Question 40: A 14-year-old boy is brought to the physician by his mother after she found an unsmoked marijuana cigarette in his bedroom. The mother reports that her son has never done anything like this before. His academic performance is excellent. When interviewed alone, the patient reports that his friends heard about smoking marijuana and acquired some from their peers to find out what it was like. He adds that he has never smoked marijuana before. He requests that his teachers not be informed because they would be very disappointed if they found out. Physical examination shows no abnormalities. On mental status examination, he is pleasant and cooperative and appears remorseful. Which of the following is the most likely diagnosis?

• Marijuana abuse
• Conduct disorder
• Parent-child relational problem
• Normal adolescence (Correct answer)
• Marijuana dependence

Correct answer: Normal adolescence

The patient's behavior, involving a single, isolated instance of curiosity about marijuana with peers, without actual use or a pattern of problematic behavior, is consistent with normal adolescent experimentation and exploration. His excellent academic performance and remorse indicate that this is not indicative of a conduct disorder or substance abuse/dependence, but rather a common developmental stage that often involves testing boundaries.

Question 41: A 14-year-old girl is brought to the physician for a well-child examination. She reports that she occasionally feels sad because “everyone else is confident except me.” She notes that she likes a new boy in her class, but she is afraid that “he doesn’t know that I exist.” She sometimes worries that she will attract his attention, but this is not a constant worry. She adds, “I know he likes this really pretty singer on TV, and I could never measure up to her. I am not sure that anyone can really relate to my situation.” She generally gets along well with friends and family. She is in the eighth grade and maintains a B average. She plays on the school soccer team and is an active member of the Girl Scouts. She does not drink alcohol or use illicit drugs. She is not sexually active. She is at the 60th percentile for height and 50th percentile for weight. She is casually dressed. Physical examination shows no abnormalities. On mental status examination, she is cooperative with a mildly anxious mood and a full range of affect. She says she is not depressed. Which of the following is the most likely diagnosis?

• Generalized anxiety disorder
• Histrionic personality disorder
• Narcissistic personality disorder
• Normal development (Correct answer)

Correct answer: Normal development

This 14-year-old girl's feelings of occasional sadness, self-consciousness, comparison to others, and worries about social acceptance and romantic interests are common and normal emotional experiences during adolescence. Her overall good functioning in school, friendships, and extracurricular activities, along with the absence of severe or persistent distress or impairment, indicates normal psychosocial development for her age.

Question 42: A chronic alcoholic presents with peripheral neuropathy and Wernicke encephalopathy. Which vitamin cofactor is deficient in pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase?

• Pyridoxine (B6)
• Cobalamin (B12)
• Riboflavin (B2)
• Thiamine (B1) (Correct answer)

Correct answer: Thiamine (B1)

Thiamine pyrophosphate (TPP) is an essential cofactor for oxidative decarboxylation complexes including pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase.

Question 43: A 90-year-old woman is brought to the emergency department 30 minutes after she fell while climbing the steps into her house. Physical examination shows tenderness over the right shin area. An x-ray of the right lower extremity shows a fracture of the tibia. A DEXA scan shows decreased bone density. Increased activity of which of the following cell types is the most likely cause of the decrease in bone mass in this patient?

• Osteoclasts (Correct answer)
• Osteoblasts
• Chondrocytes
• Osteoprogenitor cells
• Osteocytes

Correct answer: Osteoclasts

Osteoclasts are specialized cells responsible for bone resorption, which is the breakdown of bone tissue. In an elderly patient with decreased bone density (osteoporosis), there is an imbalance where the activity of osteoclasts in breaking down bone exceeds the bone formation by osteoblasts. This leads to a net loss of bone mass, making the bones fragile and prone to fractures. Chondrocytes form cartilage, osteoblasts build bone, osteocytes maintain bone, and osteoprogenitor cells are precursors to osteoblasts.

Question 44: A 2-year-old boy who recently emigrated from Somalia is brought to the physician because of a 1-day history of pain of his arms and legs. Physical examination shows pale mucous membranes and hepatosplenomegaly. Laboratory studies show a hemoglobin concentration of 8 g/dL. A peripheral blood smear shows sickle cells. Genetic analyses show a point mutation in the β-globin gene leading to a change of a GAG codon (glutamate) to a GUG codon (valine). Which of the following anticodons is most likely in the tRNA for valine?

• GAC
• GCC
• CTU
• CAC (Correct answer)
• CUC

Correct answer: CAC

The mRNA codon for valine in this patient's sickle cell mutation is GUG. Transfer RNA (tRNA) anticodons are complementary to mRNA codons, following standard base-pairing rules (G with C, U with A). Therefore, the anticodon that would pair with the GUG codon is CAC.

Question 45: Which adverse effect is most specific to thiazide diuretics compared to loop diuretics?

• Metabolic acidosis
• Ototoxicity
• Hyperglycemia and hyperuricemia (Correct answer)
• Hyponatremia

Correct answer: Hyperglycemia and hyperuricemia

Thiazides cause hyperglycemia (decreased insulin secretion and peripheral resistance) and hyperuricemia (decreased uric acid secretion), effects not seen with loop diuretics.

Question 46: A 16-year-old girl is brought to the physician because of severe acne over her face and upper back for 6 months. She has had no itching or scaling of the acne. Treatment with topical and oral antibiotics has not resolved her symptoms. Examination shows numerous papules and pustules with widespread erythema over the face and upper back. There is no hyperpigmentation. The patient requests information about beginning isotretinoin, because she says it improved her boyfriend’s acne. Which of the following is the most appropriate initial step prior to treatment with isotretinoin?

• PPD skin test
• Complete blood count with differential
• Measurement of urine β-hCG concentration (Correct answer)
• 24-Hour urine collection for measurement of creatinine clearance
• Measurement of serum thyroid-stimulating hormone concentration
• Determination of prothrombin and partial thromboplastin times

Correct answer: Measurement of urine β-hCG concentration

Isotretinoin is a highly effective treatment for severe acne but is a potent teratogen, meaning it causes severe birth defects. Therefore, it is absolutely contraindicated in pregnancy. Before initiating isotretinoin in any female of childbearing potential, a pregnancy test, such as a urine β-hCG concentration measurement, is mandatory to ensure the patient is not pregnant, along with strict contraception counseling.

Question 47: A sexually active 37-year-old woman comes to the physician because of a 2-day history of pain in the area of her genitals. Pelvic examination shows shallow, small, extremely tender ulcers with red bases in the vulvar and vaginal regions. A Tzanck smear shows the presence of multinucleated giant cells. Which of the following infectious agents is the most likely cause of these findings?

• Candida albicans
• Trichomonas vaginalis
• Treponema pallidum
• Herpes simplex virus (Correct answer)
• Chlamydia trachomatis

Correct answer: Herpes simplex virus

The presence of shallow, small, extremely tender ulcers with red bases in the vulvar and vaginal regions is highly characteristic of genital herpes. The finding of multinucleated giant cells on a Tzanck smear is a classic cytological hallmark of herpes simplex virus (HSV) infection, confirming the viral etiology. HSV causes painful vesicular lesions that rupture to form ulcers, and the Tzanck smear helps differentiate it from other causes of genital ulcers.

Question 48: A 42-year-old woman, gravida 3, para 3, comes to the physician because she has not had a menstrual period for 2 months. She reports that she had an episode of spotting 3 weeks ago. She has had no other symptoms. She has no history of abnormal Pap smears; her last Pap smear was 10 months ago. She is sexually active with her husband and uses condoms. She is 163 cm (5 ft 4 in) tall and weighs 72 kg (160 lb); BMI is 28 kg/m2 . On physical examination, the abdomen is nontender to palpation. Pelvic examination shows a slightly enlarged uterus; there are no palpable adnexal masses. Which of the following is the most appropriate next step in management?

• Measurement of serum β-hCG concentration (Correct answer)
• Measurement of serum thyroid-stimulating hormone concentration
• CT scan of the pelvis
• Endometrial biopsy
• Oral contraceptive therapy

Correct answer: Measurement of serum β-hCG concentration

In any woman of reproductive age presenting with amenorrhea or abnormal uterine bleeding, especially with a slightly enlarged uterus, the most crucial initial step is to rule out pregnancy. Despite using condoms, contraception can fail, and a quantitative serum β-hCG concentration is the most sensitive and specific test to confirm or exclude pregnancy.

Question 49: During an experimental study, an investigator finds that the regulation of cell cycle and programmed cell death may be initiated by the mitochondrion. The interaction of the mitochondrion with the activation of the caspase family of proteases and subsequent apoptosis is most likely mediated by which of the following?

• Cytochrome c release (Correct answer)
• cAMP production
• GTP binding
• Calcium release
• Nitric oxide release

Correct answer: Cytochrome c release

The mitochondrion plays a central role in initiating the intrinsic pathway of apoptosis. Upon receiving apoptotic signals, the outer mitochondrial membrane becomes permeable, leading to the release of cytochrome c from the intermembrane space into the cytosol. Cytosolic cytochrome c then binds to Apaf-1, forming the apoptosome, which activates caspase-9 and subsequently the effector caspases, leading to programmed cell death. While calcium can influence mitochondrial function, cytochrome c release is the direct mediator for caspase activation in this pathway.

Question 50: A 6-year-old boy has a large intra-abdominal mass in the midline just above the symphysis pubis. During an operation, a cystic mass is found attached to the umbilicus and the apex of the bladder. Which of the following is the most likely diagnosis?

• Meckel cyst
• Urachal cyst (Correct answer)
• Meckel diverticulum
• Omphalocele
• Hydrocele

Correct answer: Urachal cyst

The urachus is an embryonic remnant of the allantois that connects the fetal bladder to the umbilicus. If the urachus fails to involute completely, it can form a cyst, which is typically located in the midline between the umbilicus and the bladder apex, precisely matching the description of the mass found in this patient.

Question 51: A 40-year-old man undergoes total thyroidectomy for papillary thyroid cancer. Six hours postoperatively he complains of tingling around his mouth and in his fingertips. His calcium level is 7.2 mg/dL. What is the immediate treatment?

• IV calcium gluconate (Correct answer)
• Oral calcium carbonate supplementation
• IV magnesium sulfate
• Parathyroid reimplantation

Correct answer: IV calcium gluconate

Symptomatic hypocalcemia after thyroidectomy requires immediate IV calcium gluconate to prevent laryngospasm and tetany.

Question 52: A 3-year-old girl is brought to the physician by her parents because they are concerned about her behavior. They describe their daughter as stubborn and always on the go. She can rarely sit still for more than 10 minutes. She often refuses to comply with their requests and sometimes throws 3- to 5-minute temper tantrums. They report that she dawdles at bedtime and requires frequent direction and assistance in preparing for bed. Her preschool teacher notes that she is active and talkative without being disruptive and is beginning to demonstrate more interactive play with her peers. She generally sleeps through the night and occasionally wets the bed. Her appetite is good. Her first word was at the age of 11 months, and she began walking without assistance at the age of 14 months. Physical examination shows no abnormalities. On mental status examination, she initially hides behind her mother but warms to the interviewer after a few minutes and begins playing with toys in the office. Her speech is 90% intelligible, and her vocabulary is large for her age. Which of the following is the most appropriate next step in management?

• Trial of fluoxetine
• Play therapy
• Enuresis alarm
• Trial of methylphenidate
• Speech therapy
• Reassurance (Correct answer)

Correct answer: Reassurance

The described behaviors, such as being 'on the go,' having short attention spans, occasional temper tantrums, and dawdling at bedtime, are common and developmentally appropriate for a 3-year-old child. The preschool teacher's report of non-disruptive activity and interactive play further supports normal development, indicating no significant impairment or pathology. Therefore, reassurance to the parents is the most appropriate initial management.

Question 53: The blood flow through an organ is measured while the perfusion pressure is varied experimentally. An abrupt, sustained increase in perfusion pressure increases flow initially, but over the course of 1 minute, the flow returns nearly to the baseline level despite continued elevation of the perfusion pressure. The organ under study is exhibiting which of the following?

• Active hyperemia
• Autoregulation (Correct answer)
• Ischemia
• Reactive hyperemia

Correct answer: Autoregulation

This phenomenon describes autoregulation, the intrinsic ability of an organ or tissue to maintain a relatively constant blood flow despite changes in perfusion pressure. When perfusion pressure increases, the blood vessels in an autoregulating organ constrict (myogenic response) or release vasoconstrictors. This increases resistance and returns blood flow towards its baseline level, ensuring stable nutrient and oxygen delivery.

Question 54: Ten years ago, a 60-year-old woman underwent an aortic valve replacement with a porcine heterograft. She now has shortness of breath with exertion. Examination and x-ray of the chest show evidence of congestive heart failure. Which of the following is the most likely explanation for these findings?

• Embolus to the coronary circulation
• Development of a ventricular septal defect
• Development of an ascending aortic aneurysm
• Degeneration of the valve (Correct answer)
• Development of mitral stenosis

Correct answer: Degeneration of the valve

Bioprosthetic (porcine heterograft) heart valves, unlike mechanical valves, have a limited lifespan, typically 10-15 years. Over time, these valves undergo structural degeneration and calcification, leading to valve dysfunction such as stenosis or regurgitation. This degeneration results in impaired blood flow and can cause symptoms of congestive heart failure, as seen in this patient 10 years after her replacement.

Question 55: A 38-year-old man comes to the physician because of a 6-month history of occasional episodes of chest tightness, wheezing, and cough. The symptoms are often mild and resolve spontaneously. He has been otherwise healthy. His respirations are 13/min. The lungs are clear to auscultation. Cardiac examination and chest x-ray show no abnormalities. Which of the following agents is most appropriate to treat acute episodes in this patient?

• Cromolyn
• Beclomethasone
• Ipratropium
• Theophylline
• Albuterol (Correct answer)

Correct answer: Albuterol

The patient's symptoms of occasional, mild, and spontaneously resolving chest tightness, wheezing, and cough are consistent with mild intermittent asthma. For acute episodes of asthma, the most appropriate treatment is a short-acting beta-2 adrenergic agonist (SABA) like albuterol. Albuterol rapidly relaxes bronchial smooth muscle, leading to bronchodilation and quick relief of symptoms.

Question 56: A 30-year-old woman develops a high fever, diffuse erythematous rash, and hypotension during menses. Blood cultures are negative. Which mechanism best explains systemic toxicity in this condition?

• Exotoxin blocking acetylcholine release
• Superantigen cross-linking MHC II and T-cell receptor (Correct answer)
• Lipopolysaccharide binding TLR-4
• Type III hypersensitivity immune complex deposition

Correct answer: Superantigen cross-linking MHC II and T-cell receptor

TSST-1 is a superantigen that cross-links MHC class II on APCs with the Vβ region of T-cell receptors, causing massive non-specific T-cell activation and cytokine storm.

Question 57: A 23-year-old woman with chronic hepatic disease is brought to the physician because of a 6-month history of progressive behavioral and personality changes, difficulty walking, clumsiness of her arms and legs, and slurred speech. Physical examination shows facial dystonia and dysarthria. There is intention tremor, rigidity, and ataxia of all extremities. Slit-lamp examination shows a brownish ring around the cornea of both eyes. Which of the following abnormalities in plasma is most likely in this patient?

• Decreased ceruloplasmin concentration (Correct answer)
• Decreased transferrin concentration
• Decreased calcium concentration
• Increased ketones
• Increased ammonium concentration
• Increased lactate concentration

Correct answer: Decreased ceruloplasmin concentration

The patient's symptoms, including chronic hepatic disease, progressive neurological dysfunction (dystonia, tremor, ataxia, dysarthria), and Kayser-Fleischer rings (brownish corneal rings), are classic for Wilson's disease. This is an autosomal recessive disorder of copper metabolism characterized by impaired copper excretion and reduced synthesis of ceruloplasmin, the primary copper-carrying protein in plasma. Therefore, a decreased ceruloplasmin concentration is the most likely abnormality.

Question 58: A patient with multiple sclerosis develops left eye adduction failure on attempted right lateral gaze, with nystagmus of the abducting right eye. Which structure is demyelinated?

• Right abducens nucleus
• Left abducens nucleus
• Left medial longitudinal fasciculus (MLF) (Correct answer)
• Right oculomotor nucleus

Correct answer: Left medial longitudinal fasciculus (MLF)

Internuclear ophthalmoplegia (INO) results from MLF demyelination; the ipsilateral (left) eye fails to adduct on contralateral gaze, and the abducting eye shows nystagmus.

Question 59: A 3-year-old girl is brought to the emergency department 30 minutes after she tripped and fell. Physical examination shows blue sclera and edema and tenderness over the right proximal lower extremity. X-rays show a fracture of the right femur, as well as several fractures of varying ages of the left clavicle, right humerus, and right fibula. Which of the following is the most likely diagnosis?

• Ehlers-Danlos syndrome
• Achondroplasia
• Marfan syndrome
• Hurler syndrome
• Osteogenesis imperfecta (Correct answer)

Correct answer: Osteogenesis imperfecta

The combination of blue sclera and recurrent fractures from minimal trauma, especially fractures of varying ages, is pathognomonic for osteogenesis imperfecta (OI). This genetic disorder is caused by defects in type I collagen synthesis, leading to brittle bones that fracture easily. Blue sclera occurs because the thin sclera allows the underlying choroidal veins to show through.

Question 60: A 42-year-old woman, gravida 2, para 2, comes to the physician because of increasingly frequent loss of urine during the past year. She has loss of urine when she coughs, sneezes, exercises, or plays with her children. Her incontinence is never preceded by a sudden urge to void, and she does not have loss of urine at night. Her children were born after uncomplicated vaginal deliveries. She has no history of other hospital admissions or serious illness. She takes no medications. Abdominal examination shows no abnormalities. The external genitalia, vagina, and cervix appear normal. The uterus and adnexa are normal to palpation. There is loss of a small amount of urine with Valsalva maneuver. Her postvoid residual volume is 50 mL. Urinalysis shows no abnormalities. Which of the following is the most likely diagnosis?

• Vesicovaginal fistula
• Urinary tract infection
• Overactive bladder with incontinence
• Overflow incontinence
• Stress incontinence (Correct answer)

Correct answer: Stress incontinence

The patient's symptoms of involuntary urine leakage with activities that increase intra-abdominal pressure (coughing, sneezing, exercise) and the absence of urgency or nocturnal incontinence are classic for stress incontinence. The finding of urine loss with a Valsalva maneuver and a normal postvoid residual volume further supports this diagnosis, indicating urethral hypermobility or intrinsic sphincter deficiency.

Question 61: A dataset has a mean, median, and mode that are all equal. Which of the following BEST describes this distribution?

• Positively skewed
• Bimodal
• Negatively skewed
• Normal (bell-shaped) (Correct answer)

Correct answer: Normal (bell-shaped)

When mean, median, and mode are equal, the distribution is symmetric and follows a normal (Gaussian) bell-shaped curve.

Question 62: A 3-year-old with Down syndrome is found to have an atrioventricular septal defect. Which chromosomal location is the TRISOMY associated with?

• Chromosome 22
• Chromosome 13
• Chromosome 18
• Chromosome 21 (Correct answer)

Correct answer: Chromosome 21

Down syndrome results from trisomy 21 and is strongly associated with AVSD (endocardial cushion defect).

Question 63: A 24-year-old nulligravid woman is brought to the emergency department after a syncopal episode at work. She has had progressively severe cramps in the lower abdomen over the past 6 hours. She has had spotty vaginal bleeding for 2 days; her last menstrual period began 7 weeks ago. She is diaphoretic and anxious. Her temperature is 37°C (98.6°F), pulse is 130/min, respirations are 26/min, and blood pressure is 80/60 mm Hg. Examination shows blood in the vaginal vault and diffuse abdominal tenderness; there is pain with cervical motion. Which of the following is the most appropriate next step in management?

• Transfusion of type-specific blood
• Culdocentesis
• Intravenous administration of broad-spectrum antibiotics
• Intravenous administration of fluids (Correct answer)
• Transfusion of O-negative blood

Correct answer: Intravenous administration of fluids

This patient presents with classic signs of hypovolemic shock (tachycardia, hypotension, syncope, diaphoresis) and symptoms highly suggestive of a ruptured ectopic pregnancy (amenorrhea, vaginal bleeding, severe abdominal pain, cervical motion tenderness). The immediate priority in managing hypovolemic shock is rapid fluid resuscitation to stabilize her hemodynamics. Intravenous administration of crystalloid fluids is the most appropriate first step to restore circulating volume and improve blood pressure.

Question 64: A 70-year-old man with terminal pancreatic cancer is admitted to the hospital because of severe shortness of breath. He has no documented advance care plans. His three children tell the physician that they want everything possible to be done for their father, including cardiopulmonary resuscitation (CPR) and intubation, if necessary. The patient is cachectic and unaware of his surroundings. Which of the following initial responses by the physician is most appropriate?

• “You are just prolonging the inevitable. Your father is going to die.”
• “I know that you are distressed about your father’s illness, but you must accept that he will die soon.”
• “Relatives in this type of situation feel distressed, and they want to prolong the life of their loved one unnecessarily.”
• “I hear you, and I understand how difficult it must be for you to see your father ill. Let’s talk more about the options.” (Correct answer)
• “I want you to reconsider your decision about CPR and intubation. Your father’s prognosis is very poor.”

Correct answer: “I hear you, and I understand how difficult it must be for you to see your father ill. Let’s talk more about the options.”

In emotionally charged end-of-life discussions, it is crucial to first acknowledge and validate the family's distress and wishes. This empathetic approach builds rapport and opens the door for a more productive conversation about the patient's prognosis, the futility of aggressive interventions, and alternative care options like palliative care, without immediately dismissing their desires.

Question 65: A 57-year-old woman comes to the physician because of a 2-year history of difficulty sleeping. After she gets into bed at night, her legs feel cold and crampy, and she cannot settle into a comfortable position. Walking around temporarily relieves her symptoms. She also has difficulty sitting for a prolonged period of time. She has a mild anxiety disorder but takes no medications. Vital signs are within normal limits. Examination shows no abnormalities. Which of the following is the most likely diagnosis?

• Parkinson disease
• Benign fasciculations
• Major depressive disorder
• Restless legs syndrome (Correct answer)
• REM sleep behavior disorder
• Stiff-person syndrome

Correct answer: Restless legs syndrome

The patient's description of uncomfortable sensations in her legs, particularly at night, that compel her to move them, and which are temporarily relieved by walking, is the hallmark of restless legs syndrome (RLS). RLS is a neurological disorder characterized by an irresistible urge to move the legs, often accompanied by unpleasant sensations, typically worse during periods of rest and in the evening or night.

Question 66: A 3-year-old child presents with fever, neck stiffness, and petechial rash. CSF shows glucose 30 mg/dL (serum 90), protein 180 mg/dL, WBC 1,200 (90% PMN). What organism is most likely?

• Listeria monocytogenes
• Streptococcus pneumoniae
• Haemophilus influenzae
• Neisseria meningitidis (Correct answer)

Correct answer: Neisseria meningitidis

N. meningitidis classically causes bacterial meningitis with petechial/purpuric rash in children and young adults and is the most common cause of epidemic meningitis.

Question 67: Ligand binding to a Gs-protein coupled receptor primarily leads to:

• Activation of adenylyl cyclase and increased intracellular cAMP (Correct answer)
• Direct opening of ligand-gated ion channels
• Direct DNA binding to regulate transcription
• Activation of phospholipase C and IP3/DAG production

Correct answer: Activation of adenylyl cyclase and increased intracellular cAMP

Gs-coupled receptors activate adenylyl cyclase via the Gαs subunit, increasing cAMP and activating protein kinase A.

Question 68: A 14-year-old girl is brought to the physician because of a recent growth spurt of 15 cm (6 in) during the past year. She also has had increasing fatigue and palpitations during this period. Her paternal aunt has a history of palpitations and severe myopia. She is at the 95th percentile for height and 50th percentile for weight. Physical examination shows a long, thin face. Ophthalmologic examination shows dislocated lenses. Cardiac examination shows a hyperdynamic precordium with early click and systolic murmur. Echocardiography shows an enlarged aortic root and mitral valve prolapse. Abnormal synthesis of which of the following proteins is the most likely cause of this patient’s disorder?

• Fibroblast growth factor R3
• Elastin
• PAX 6
• Fibrillin-1 (Correct answer)
• Neurofibromin
• Laminin
• Collagen, type I

Correct answer: Fibrillin-1

The patient's tall stature, long thin face, dislocated lenses, and cardiovascular abnormalities like an enlarged aortic root and mitral valve prolapse are characteristic features of Marfan syndrome. This autosomal dominant disorder results from a mutation in the *FBN1* gene, which encodes fibrillin-1. Fibrillin-1 is a key component of elastic fibers, and its abnormal synthesis leads to weakened connective tissue throughout the body, particularly affecting the skeletal, ocular, and cardiovascular systems.

Question 69: During the relative refractory period of a neuronal action potential, what stimulus is required to trigger another action potential?

• A subthreshold stimulus
• No stimulus — spontaneous firing occurs
• The same threshold stimulus as at rest
• A suprathreshold (stronger-than-normal) stimulus (Correct answer)

Correct answer: A suprathreshold (stronger-than-normal) stimulus

During the relative refractory period, some K+ channels remain open, raising the threshold so only a suprathreshold stimulus can trigger another action potential.

Question 70: A 38-year-old woman with MDD fails two adequate trials of SSRIs. She has no contraindications. Which augmentation strategy has the strongest evidence for treatment-resistant depression?

• Switching to a tricyclic antidepressant only
• Adding methylphenidate
• Adding lithium or atypical antipsychotic (Correct answer)
• Adding buspirone

Correct answer: Adding lithium or atypical antipsychotic

Augmentation with lithium or atypical antipsychotics (e.g., aripiprazole, quetiapine) has the most robust evidence for treatment-resistant depression.

Question 71: A 62-year-old man comes to the physician because of burning pain and tenderness of his right great toe 1 day after heavy ethanol consumption. Physical examination shows erythema, swelling, warmth, and tenderness of the right great toe. After a 2-week course of nonsteroidal anti-inflammatory drug treatment, his symptoms decrease in severity but do not completely resolve. The serum concentration of which of the following is most likely increased in this patient?

• Carotene
• Creatinine
• Calcium
• Orotic acid
• Iron
• Phosphate
• Uric acid (Correct answer)

Correct answer: Uric acid

The patient's symptoms of acute, severe pain, swelling, warmth, and erythema in the great toe, particularly after heavy ethanol consumption, are classic for an acute attack of gout. Gout is caused by the deposition of monosodium urate crystals in joints, which occurs when serum uric acid concentrations are elevated. Ethanol consumption can exacerbate gout by increasing uric acid production and decreasing its renal excretion.

Question 72: A 28-year-old man with a history of intravenous drug use comes to the physician because of a 6-week history of fever, nonproductive cough, chills, and progressive shortness of breath. His temperature is 39°C (102.2°F), pulse is 110/min, respirations are 32/min and regular, and blood pressure is 120/80 mm Hg. Physical examination shows a white, patchy, loosely adherent exudate on the buccal mucosa bilaterally. A chest x-ray shows bilateral interstitial infiltrates. After receiving treatment for pneumonia, he agrees to participate in a clinical study of the effects of interleukin-2 (IL-2). After administration of IL-2, which of the following hematologic changes is most likely in this patient?

• Decreased platelet count
• Decreased erythrocytes
• Increased platelet count
• Decreased CD4+ T lymphocytes
• Increased erythrocytes
• Increased CD4+ T lymphocytes (Correct answer)

Correct answer: Increased CD4+ T lymphocytes

The patient's history of HIV and opportunistic infections (Pneumocystis pneumonia, oral candidiasis) indicates significant immunosuppression, typically associated with low CD4+ T lymphocyte counts. Interleukin-2 (IL-2) is a cytokine that stimulates the proliferation, differentiation, and activation of T lymphocytes, particularly CD4+ and CD8+ T cells. Therefore, administration of IL-2 is most likely to lead to an increase in CD4+ T lymphocytes, aiming to bolster the immune response.

Question 73: A 70-year-old man is admitted to the hospital for elective coronary artery bypass grafting. On the day of his operation, an asymptomatic carotid bruit is found. Which of the following is the most appropriate immediate next step in diagnosis?

• MRI of the brain
• Cerebral angiography
• PET scan of the brain
• Duplex scan of the neck (Correct answer)
• CT scan of the head

Correct answer: Duplex scan of the neck

An asymptomatic carotid bruit indicates turbulent blood flow in the carotid artery, suggesting potential carotid artery stenosis. Before major surgery like coronary artery bypass grafting, it is crucial to assess the degree of stenosis to determine the risk of perioperative stroke. A duplex ultrasound of the neck is the most appropriate, non-invasive initial diagnostic step to evaluate carotid artery patency and quantify any stenosis.

Question 74: A 72-year-old man with hypertension presents with palpitations. ECG shows irregularly irregular rhythm with absent P waves. He has no prior anticoagulation history. CHA2DS2-VASc score is 3. What is the most appropriate management for stroke prevention?

• Warfarin with target INR 2–3
• Direct oral anticoagulant (e.g., apixaban) (Correct answer)
• No anticoagulation needed
• Aspirin 81 mg daily

Correct answer: Direct oral anticoagulant (e.g., apixaban)

A CHA2DS2-VASc score ≥2 in men with atrial fibrillation warrants anticoagulation; DOACs are preferred over warfarin for non-valvular AF due to better efficacy and safety profile.

Question 75: Schwann cells in the peripheral nervous system primarily function to:

• Regulate synaptic neurotransmitter levels
• Produce cerebrospinal fluid
• Phagocytose cellular debris in the CNS
• Myelinate peripheral axons to increase conduction velocity (Correct answer)

Correct answer: Myelinate peripheral axons to increase conduction velocity

Schwann cells wrap peripheral axons in myelin sheaths, enabling saltatory conduction and dramatically increasing action potential propagation speed.

Question 76: A 45-year-old man is brought to the physician by his spouse. He has been drinking heavily since he was passed over for a job promotion 3 days ago. He stayed in bed over the weekend. He has no personal history of psychiatric disorders and no personal or family history of alcohol abuse. He is crying and states, “I can’t believe it,” when addressed. When asked what he will do, he states, “I don’t know, but if I don’t go back to work tomorrow, I’ll lose my job.” Which of the following is the most likely diagnosis?

• Adjustment disorder with depressed mood (Correct answer)
• Dysthymic disorder
• Substance abuse
• Bipolar disorder
• Major depressive disorder

Correct answer: Adjustment disorder with depressed mood

Adjustment disorder with depressed mood is characterized by the development of emotional or behavioral symptoms in response to an identifiable stressor, occurring within 3 months of the onset of the stressor. The patient's symptoms (heavy drinking, staying in bed, crying, feeling overwhelmed) developed directly after being passed over for a promotion and are causing significant distress and functional impairment, fitting the criteria for an adjustment disorder. The symptoms are not severe or prolonged enough to meet criteria for major depressive disorder.

Question 77: A 27-year-old G1P0 is found to have a missed abortion at 10 weeks on ultrasound. She chooses medical management rather than expectant or surgical treatment. Which medication is most appropriate?

• Methotrexate 50 mg/m² IM
• Misoprostol 800 mcg vaginally (Correct answer)
• Oxytocin IV infusion
• Mifepristone 600 mg PO alone

Correct answer: Misoprostol 800 mcg vaginally

Misoprostol, a prostaglandin E1 analogue, is used for medical management of missed abortion to cause cervical ripening and uterine contractions leading to expulsion.

Question 78: A 22-year-old woman with a 10-year history of asthma comes to the physician because she has had to increase her use of her albuterol inhaler during the past 6 weeks. Her asthma was previously well controlled with inhaled glucocorticoids. She has a 2-year history of generalized anxiety disorder controlled with fluoxetine and a 5-year history of migraines. The migraines were well controlled with sumatriptan until 4 months ago when she began to have headaches twice weekly; propranolol was added to her regimen at that time. She has been taking an oral contraceptive for the past year. She says she has been under increased stress at graduate school and in her personal life during the past 3 months; during this period, she has been drinking an average of four cups of coffee daily (compared with her usual one cup daily). She does not drink alcohol or use illicit drugs. She appears mildly anxious but is not in respiratory distress. Scattered end-expiratory wheezes are heard. The remainder of the examination shows no abnormalities. Which of the following is the most likely cause of the exacerbation of this patient’s asthma?

• Oral contraceptive therapy
• Fluoxetine therapy
• Propranolol therapy (Correct answer)
• Sumatriptan therapy
• Increased caffeine intake

Correct answer: Propranolol therapy

Propranolol is a non-selective beta-blocker, meaning it blocks both beta-1 and beta-2 adrenergic receptors. Beta-2 receptors are abundant in the bronchial smooth muscle, and their blockade by propranolol can lead to bronchoconstriction. This effect directly counteracts the bronchodilatory action of albuterol and can significantly exacerbate asthma symptoms, making it a contraindicated medication for most asthmatic patients.

Question 79: A 25-year-old butcher has had severe episodic pain in his right thumb and right second and third digits for 2 months. The pain frequently awakens him from sleep. He has decreased sensation over the palmar surface of the thumb and index and long fingers of the right hand and atrophy of the thenar muscle mass. Compression of which of the following nerves is the most likely cause?

• Musculocutaneous
• Radial
• Median (Correct answer)
• Ulnar
• Posterior interosseous

Correct answer: Median

The patient's symptoms, including severe episodic pain in the thumb, index, and middle fingers, decreased sensation over the palmar surface of these digits, and thenar muscle atrophy, are classic for carpal tunnel syndrome. This condition results from compression of the median nerve as it passes through the carpal tunnel in the wrist. The median nerve provides sensory innervation to these specific fingers and motor innervation to the thenar muscles.

Question 80: A 22-year-old man is brought to the emergency department because of a suprahyoid stab wound that extends from one side of the neck to the other. His tongue deviates to the right when protruded; there is no loss of sensory modality on the tongue. The injury most likely involves which of the following nerves?

• Right hypoglossal (Correct answer)
• Left hypoglossal
• Right glossopharyngeal
• Right lingual
• Left vagus

Correct answer: Right hypoglossal

The hypoglossal nerve (CN XII) innervates the intrinsic and extrinsic muscles of the tongue, primarily controlling tongue movement. Damage to the hypoglossal nerve results in ipsilateral tongue weakness and atrophy. When protruded, the tongue deviates *towards* the side of the lesion due to the unopposed action of the contralateral genioglossus muscle; therefore, right deviation indicates a right hypoglossal nerve injury.

Question 81: A previously healthy 32-year-old man comes to the emergency department because of a 3-day history of pain and swelling of his right knee. Two weeks ago, he injured his right knee during a touch football game and has had swelling and bruising for 5 days. One week ago, he underwent extraction of a molar for severe dental caries. He is sexually active with one male partner and uses condoms consistently. HIV antibody testing was negative 3 months ago. His temperature is 38.6°C (101.5°F), pulse is 100/min, and blood pressure is 120/60 mm Hg. Examination of the right knee shows warmth, erythema, and a joint effusion. Flexion and extension of the right knee are severely limited. An x-ray of the knee confirms the joint effusion. Which of the following is the most appropriate next step in diagnosis?

• MRI of the knee
• Venous Doppler ultrasonography
• Bone scan
• Arthroscopic exploration of the knee
• Arthrocentesis (Correct answer)

Correct answer: Arthrocentesis

The patient presents with acute monoarticular arthritis (warmth, erythema, effusion, severe pain, fever). Given his recent dental procedure (a potential source of bacteremia) and a prior knee injury (which can predispose to infection), septic arthritis is a significant concern. Arthrocentesis (joint aspiration) is the most appropriate next step to obtain synovial fluid for analysis (cell count, Gram stain, culture) to definitively diagnose or rule out septic arthritis, which requires urgent treatment.

Question 82: An 82-year-old man is admitted to the hospital because nursing staff in his skilled nursing care facility report that he has appeared sad and depressed during the past 2 months. It is reported that he has a history of psychiatric illness, but details are not provided. He has been taking olanzapine, paroxetine, and haloperidol for 2 years. He does not appear to be in acute distress. He is 160 cm (5 ft 3 in) tall and weighs 48 kg (105 lb); BMI is 19 kg/m2 . Physical examination shows 2+ cogwheel rigidity of the upper extremities. Neurologic examination shows psychomotor retardation. On mental status examination, he is alert and generally pleasant and cooperative. His affect has little intensity or range. He says he does not feel depressed or anxious. Laboratory findings are within the reference range. Which of the following is the most likely cause of this patient’s current symptoms?

• Drug-induced parkinsonism (Correct answer)
• Adjustment disorder
• Akathisia
• Dementia, Alzheimer type
• Major depressive disorder

Correct answer: Drug-induced parkinsonism

The patient's new onset of cogwheel rigidity, psychomotor retardation, and flat affect, despite denying depression, are classic extrapyramidal symptoms consistent with parkinsonism. Given his medication regimen including haloperidol (a typical antipsychotic) and olanzapine (an atypical antipsychotic, but still with D2 antagonism), drug-induced parkinsonism is the most likely cause. These medications block dopamine D2 receptors, leading to a functional dopamine deficiency that mimics Parkinson's disease.

Question 83: During cardiac embryology, the interventricular septum forms primarily from which structure?

• Endocardial cushions alone
• Neural crest cells migrating into the heart
• Muscular septum growing from apex plus membranous portion from cushions (Correct answer)
• Septum primum growing downward

Correct answer: Muscular septum growing from apex plus membranous portion from cushions

The muscular interventricular septum grows up from the ventricular apex, and the membranous portion is completed by tissue from the endocardial cushions (atrioventricular septal tissue).

Question 84: A 3-week-old infant is brought to the physician by his mother because of a 1-week history of increasingly frequent vomiting. She says that at first he vomited occasionally, but now he vomits after every feeding. The vomitus is nonbilious and consists of breast milk. He has had fewer wet diapers during the past 2 days. He was born at term following an uncomplicated pregnancy and initially fed well. He appears lethargic and dehydrated. A 1 × 2-cm, firm, mobile, olive-shaped mass is palpated immediately to the left of the epigastrium. Which of the following is the most likely diagnosis?

• Pyloric stenosis
• Intussusception
• Congenital megacolon (Hirschsprung disease)
• Duodenal atresia
• Midgut volvulus

The infant's presentation of progressive, nonbilious vomiting after every feeding, dehydration, and a palpable 'olive-shaped' mass in the epigastrium is classic for pyloric stenosis. This condition involves hypertrophy of the pyloric muscle, which obstructs gastric outflow. The nonbilious nature of the vomitus indicates the obstruction is proximal to the ampulla of Vater, preventing bile from entering the stomach.

Question 85: A previously healthy 67-year-old woman comes to the physician with her husband because of a 4-month history of a resting tremor of her right arm. Her husband reports that her movements have been slower and that she appears less stable while walking. Examination shows increased muscle tone in the upper extremities that is greater on the right than on the left. There is decreased right arm swing. Her gait is slow and shuffling. Which of the following is the most likely explanation for this patient’s symptoms?

• Decreased dopaminergic input to the striatum (Correct answer)
• Excessive thalamic output of norepinephrine
• Bilateral frontal lobe degeneration
• Excessive output of oxytocin
• Decreased serotonergic activity in the brain stem

Correct answer: Decreased dopaminergic input to the striatum

The patient's symptoms—resting tremor, slowed movements (bradykinesia), unstable gait (postural instability), increased muscle tone (rigidity), and decreased arm swing—are classic manifestations of Parkinson's disease. This neurodegenerative disorder is primarily caused by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta, leading to a significant reduction in dopamine input to the striatum and subsequent disruption of basal ganglia function.

Question 86: A 37-year-old man with type 1 diabetes mellitus comes to the physician for a routine examination. His only medication is insulin. His pulse is 72/min, respirations are 12/min, and blood pressure is 138/88 mm Hg. Funduscopic examination shows microaneurysms and hemorrhages. Sensation to vibration and light touch is decreased over the lower extremities. His serum creatinine concentration is 1.6 mg/dL. A 24-hour urine collection shows 550 mg of protein. Treatment with which of the following is most likely to slow progression of this patient’s renal disease?

• Hydrochlorothiazide
• Clonidine
• Hydralazine
• Lisinopril (Correct answer)
• Atenolol

Correct answer: Lisinopril

The patient has evidence of diabetic nephropathy, characterized by proteinuria and elevated serum creatinine. Angiotensin-converting enzyme (ACE) inhibitors, such as lisinopril, are the cornerstone of treatment for diabetic nephropathy. They reduce intraglomerular pressure by dilating the efferent renal arteriole, thereby decreasing proteinuria and significantly slowing the progression of renal disease.

Question 87: A 10-year-old boy is brought to the emergency department 15 minutes after he sustained abdominal injuries in a motor vehicle collision. Physical examination shows massive ecchymoses over the trunk and abdomen. A CT scan shows internal bleeding. The patient undergoes operative removal of a portion of the lower left lobe of the lung, the left lobe of the liver, half of the left kidney, half of the spleen, and a 2-foot section of the small intestine. Assuming survival of the acute trauma, which of the following organs is likely to have the most complete regeneration in this patient?

• Liver (Correct answer)
• Small intestine
• Spleen
• Lung
• Kidney

Correct answer: Liver

Among the listed organs, the liver possesses a remarkable capacity for regeneration, capable of restoring its mass and function even after significant tissue loss. This regenerative ability is primarily due to the proliferation of existing hepatocytes. In contrast, the kidney, lung, spleen, and small intestine have more limited regenerative capabilities, typically undergoing repair by fibrosis or partial restoration rather than complete regeneration of lost tissue.

Question 88: A 5-year-old boy with Down syndrome is admitted to the hospital because of a 1-month history of fatigue, intermittent fever, and weakness. Results from a peripheral blood smear taken during his evaluation are indicative of possible acute lymphoblastic leukemia. The physician recommends a bone marrow aspiration to confirm the diagnosis and subsequent cytogenetic studies as needed. The patient’s parents refuse to consent to the procedure because they think such an invasive test will cause their son too much unnecessary pain. Without confirmation of the diagnosis and results from cytogenetic testing, the patient’s treatment may be adversely affected. Which of the following is the most appropriate next step for the physician?

• Do the necessary procedure despite the parents’ objections
• Accede to the parents’ wishes to spare their son further pain
• Discuss options to manage the potential pain during the procedure (Correct answer)
• Consult child protective services
• Explain that the child will die if the procedure is refused

Correct answer: Discuss options to manage the potential pain during the procedure

The parents' refusal stems from a concern about their child's pain, not a rejection of medical care itself. The most appropriate initial step is to address their specific concern by discussing pain management strategies (e.g., sedation, local anesthesia) for the procedure. This demonstrates empathy, builds trust, and may alleviate their fears, allowing them to consent to the necessary diagnostic test.

Question 89: A 47-year-old woman is brought to the physician by her husband because of bizarre behavior for 1 week. Her husband says that she makes no sense when she speaks and seems to be seeing things. She also has had difficulty sleeping for 2 months and has gained approximately 9 kg (20 lb) during the past 5 months. During this time, she has been moody and easily fatigued. He also notes that the shape of her face has become increasingly round and out of proportion with the rest of her body despite her weight gain. She has no history of psychiatric or medical illness. She is 160 cm (5 ft 3 in) tall and weighs 70 kg (155 lb); BMI is 28 kg/m2 . Her pulse is 98/min, respirations are 8/min, and blood pressure is 148/92 mm Hg. Physical examination shows truncal obesity and ecchymoses over the upper and lower extremities. Neurologic examination shows no focal findings. Mental status examination shows pressured speech and a disorganized thought process. There is evidence of visual and auditory hallucinations. Urine toxicology screening is negative. Which of the following is the most likely diagnosis?

• Brief psychotic disorder
• Schizophrenia
• Major depressive disorder with psychotic features
• Schizotypal personality disorders
• Psychotic disorder due to a general medical condition (Correct answer)

Correct answer: Psychotic disorder due to a general medical condition

The patient presents with acute psychotic symptoms (hallucinations, disorganized thought, pressured speech) alongside several physical signs highly suggestive of Cushing's syndrome, including a round face, truncal obesity, ecchymoses, weight gain, and hypertension. The rapid onset of psychosis in the context of these clear physical findings points to a general medical condition, likely Cushing's, as the underlying cause of her psychiatric symptoms.

Question 90: A 35-year-old woman delivers a newborn who develops meningitis. The mother has a streptococcus isolated from her vagina. The organism agglutinates with antiserum directed against type B surface carbohydrate. The virulence of this organism is related to a bacterial constituent that interferes with which of the following host phagocyte functions?

• Intracellular killing
• Chemotaxis
• Pseudopod formation
• Ingestion (Correct answer)
• Aggregation

Correct answer: Ingestion

Group B Streptococcus (GBS), or Streptococcus agalactiae, is a major cause of neonatal meningitis and sepsis. Its primary virulence factor is its polysaccharide capsule, particularly the type B capsule mentioned. This capsule interferes with the host's immune response by preventing the ingestion (phagocytosis) of the bacteria by macrophages and neutrophils. By evading phagocytosis, GBS can survive and proliferate in the host, leading to invasive infections.

Question 91: A study reports a p-value of 0.03 with alpha set at 0.05. What is the correct interpretation?

• There is a 3% probability of obtaining results this extreme if the null hypothesis is true (Correct answer)
• The finding is clinically significant
• The study has 97% statistical power
• There is a 3% probability the null hypothesis is true

Correct answer: There is a 3% probability of obtaining results this extreme if the null hypothesis is true

A p-value represents the probability of observing results at least as extreme as those found, assuming the null hypothesis is true — not the probability that the null is true.

Question 92: A 28-year-old woman presents with a 3-cm tender mass in the right breast that has been present for 2 weeks. Ultrasound shows a well-circumscribed, anechoic, cystic structure. Fine-needle aspiration yields clear fluid and the mass resolves. What is the appropriate next step?

• Core needle biopsy
• Repeat mammogram in 6 months
• Excisional biopsy
• Reassurance and routine follow-up (Correct answer)

Correct answer: Reassurance and routine follow-up

A simple cyst that resolves completely after aspiration of clear fluid requires only routine follow-up with no further intervention.

Question 93: A 27-year-old nulligravid woman and her husband have been unable to conceive for 12 months. She has never used contraception. Menses occur at 28-day intervals, and her last menstrual period was 2 weeks ago. She had a single episode of pelvic inflammatory disease 4 years ago and was treated with oral antibiotics. Vaginal examination shows no abnormalities. Cervical cultures are normal. Which of the following is the most appropriate next step in diagnosis?

• Hysterosalpingography (Correct answer)
• Reevaluation in 6 months
• Sperm penetration assay
• Endometrial biopsy
• Ultrasonography of the abdomen

Correct answer: Hysterosalpingography

Infertility is defined as the inability to conceive after 12 months of unprotected intercourse for women under 35. Given her history of pelvic inflammatory disease (PID), there is a significant risk of tubal damage and obstruction. Hysterosalpingography (HSG) is the most appropriate next step to evaluate tubal patency and uterine cavity abnormalities, which are common causes of infertility after PID.

Question 94: A 47-year-old man comes to the physician because of a 4-week history of increased thirst and urination. He has had a 23-kg (50-lb) weight gain during the past 2 years. He has no history of serious illness and takes no medications. His mother and maternal grandfather have type 2 diabetes mellitus. The patient does not smoke and drinks one beer every night. He is 175 cm (5 ft 9 in) tall and now weighs 104 kg (230 lb); BMI is 34 kg/m2 . His pulse is 90/min, and blood pressure is 150/88 mm Hg. The remainder of the examination shows no abnormalities. His serum glucose concentration is 330 mg/dL. Which of the following is the most likely underlying cause of this patient’s increased serum glucose concentration?

• Chronic pancreatitis
• Insulin resistance (Correct answer)
• Pancreatic cancer
• Autoimmune destruction of islet cells
• Exogenous production of corticosteroids

Correct answer: Insulin resistance

This patient presents with classic features of type 2 diabetes mellitus, including significant weight gain leading to obesity (BMI 34), hypertension, and marked hyperglycemia (serum glucose 330 mg/dL). His family history of type 2 diabetes further supports this diagnosis. The underlying cause of type 2 diabetes is primarily insulin resistance, where target cells fail to respond adequately to insulin, leading to compensatory hyperinsulinemia and eventual pancreatic beta-cell exhaustion.

Question 95: A 50-year-old Ohio River valley farmer develops pulmonary nodules and skin lesions with verrucous borders. Biopsy shows broad-based budding yeast. Which organism is responsible?

• Paracoccidioides brasiliensis
• Blastomyces dermatitidis (Correct answer)
• Coccidioides immitis
• Histoplasma capsulatum

Correct answer: Blastomyces dermatitidis

Blastomyces dermatitidis causes blastomycosis characterized by broad-based budding yeast on histology and verrucous skin lesions; it is endemic to the Ohio and Mississippi River valleys and Great Lakes region.

Question 96: A 70-year-old man with systolic heart failure (EF 30%) presents with worsening dyspnea and bilateral leg edema. His current medications include lisinopril and carvedilol. Which additional drug has been shown to reduce mortality in this patient?

• Spironolactone (Correct answer)
• Amlodipine
• Hydralazine
• Digoxin

Correct answer: Spironolactone

Spironolactone (an aldosterone antagonist) reduces mortality in patients with reduced EF heart failure when added to ACE inhibitor and beta-blocker therapy.

Question 97: A 13-year-old girl is brought to the physician because of a 1-year history of intermittent irregular vaginal bleeding; the bleeding ranges from spotting to heavier than a normal menstrual period, occurs every 2 to 8 weeks, and lasts 10 to 30 days. Examination shows a pink, well-rugated vagina with no discharge; the cervix appears normal. The uterus is 6 cm in length, regular in contour, and nontender. There are palpable, normal-sized, nontender ovaries. Which of the following is the most appropriate pharmacotherapy to alleviate this patient’s symptoms?

• Oral contraceptives (Correct answer)
• Thyroid hormone
• Tetracycline
• Gonadotropin-releasing hormone agonist
• Continuous low-dose estrogen

Correct answer: Oral contraceptives

Irregular and heavy menstrual bleeding in an adolescent, especially within the first few years post-menarche, is commonly due to anovulatory cycles, leading to dysfunctional uterine bleeding. Oral contraceptives (OCPs) are the most appropriate pharmacotherapy as they regulate the menstrual cycle, reduce bleeding, and provide contraception by stabilizing the endometrial lining and inducing regular withdrawal bleeds.

Question 98: A screening test has 90% sensitivity and 80% specificity. The disease prevalence is 10%. What is the approximate positive predictive value (PPV)?

• 33% (Correct answer)
• 50%
• 80%
• 90%

Correct answer: 33%

PPV = (sensitivity × prevalence) / [(sensitivity × prevalence) + (1−specificity)(1−prevalence)] = (0.9×0.1) / (0.9×0.1 + 0.2×0.9) ≈ 33%.

Question 99: Which enzyme is unique to gluconeogenesis and is not used in glycolysis?

• Phosphoglycerate kinase
• Enolase
• Phosphoenolpyruvate carboxykinase (PEPCK) (Correct answer)
• Phosphoglycerate mutase

Correct answer: Phosphoenolpyruvate carboxykinase (PEPCK)

PEPCK converts oxaloacetate to PEP, bypassing the irreversible pyruvate kinase reaction of glycolysis; it is exclusive to gluconeogenesis.

Question 100: A 39-year-old woman comes to the physician for a follow-up examination because she recently was diagnosed with hypertension. Her blood pressure is 156/100 mm Hg. Physical examination shows no other abnormalities. Serum studies show normal findings. A 24-hour urine collection shows three times the normal excretion of epinephrine and metanephrine. The excessive epinephrine production in this patient is most likely caused by which of the following cell types?

• Juxtaglomerular
• Chromaffin (Correct answer)
• Zona fasciculata
• Zona reticularis
• Zona glomerulosa

Correct answer: Chromaffin

The elevated urinary excretion of epinephrine and metanephrine is highly suggestive of a pheochromocytoma, a tumor of the adrenal medulla. Chromaffin cells, located in the adrenal medulla, are specialized neuroendocrine cells that synthesize and secrete catecholamines, including epinephrine and norepinephrine. These cells are the source of excessive catecholamine production in pheochromocytoma, leading to hypertension.

Question 101: A 70-year-old woman has a lytic skull lesion, hypercalcemia, anemia, and rouleaux formation on peripheral smear. Urine protein electrophoresis shows a Bence Jones protein. Which cells are malignant?

• NK cells
• Myeloid precursors
• B lymphocytes
• Plasma cells (Correct answer)

Correct answer: Plasma cells

Multiple myeloma is a malignancy of terminally differentiated plasma cells that produce monoclonal immunoglobulin (M protein) and free light chains (Bence Jones proteins).

Question 102: A 29-year-old man who emigrated from Scotland 3 years ago is brought to the emergency department because of severe shortness of breath for 2 hours. He has a debilitating condition that began 2 years ago with an odd sticky feeling of his skin, but physical examination at that time showed no abnormalities. His condition has progressed to include severe major depressive disorder, dementia, unsteady gait, difficulty walking, and impaired coordination. He now is confined to a wheelchair and has severe dementia and the inability to speak. There is no family history of a similar condition. On arrival, his respirations are 24/min, and he dies shortly thereafter. At autopsy, examination of the brain shows a spongiform encephalopathy. Which of the following is the most likely diagnosis?

• Dementia, Alzheimer type
• Pick disease
• Parkinson disease
• Frontotemporal dementia
• Variant Creutzfeldt-Jakob disease (Correct answer)

Correct answer: Variant Creutzfeldt-Jakob disease

The patient's young age, rapid progression of psychiatric symptoms (severe depression), sensory complaints ('sticky feeling'), neurological decline (dementia, ataxia), and spongiform encephalopathy on autopsy are highly characteristic of variant Creutzfeldt-Jakob disease (vCJD). His emigration from Scotland is also relevant, as vCJD is linked to the consumption of beef products contaminated with bovine spongiform encephalopathy (BSE) prions, which was prevalent in the UK.

Question 103: A 32-year-old woman comes to the physician because of a 3-week history of depressed mood. She works as a local news anchor. She says that she has always had a busy schedule, but lately she has not had her usual amount of energy and has had difficulty getting up and going to work. She describes herself as normally a “hyper” person with energy to perform multiple tasks. During the past 10 years, she has had similar episodes in which she has had depressed mood associated with a decreased energy level that makes her feel “slowed down.” The episodes never last more than a few weeks. She sometimes goes through periods when she feels a surge in energy, sleeps very little, feels at the top of her mental powers, and is able to generate new ideas for the news station; these episodes never last more than 5 days. She says that she loves feeling this way and wishes the episodes would last longer. She takes no medications. She does not drink alcohol or use illicit drugs. Her temperature is 37°C (98.6°F), pulse is 70/min, and blood pressure is 125/80 mm Hg. Physical examination shows no abnormalities. Mental status examination shows a depressed mood and flat affect. Which of the following is the most likely diagnosis?

• Cyclothymic disorder (Correct answer)
• Major depressive disorder
• Dysthymic disorder
• Mood disorder due to a general medical condition
• Attention-deficit/hyperactivity disorder

Correct answer: Cyclothymic disorder

Cyclothymic disorder is characterized by a chronic, fluctuating mood disturbance involving numerous periods of hypomanic symptoms and numerous periods of depressive symptoms, none of which meet the full criteria for a hypomanic episode or a major depressive episode. The patient's history of recurrent 'slowed down' depressive periods and 'surge in energy' hypomanic periods (lasting less than 5 days and not causing significant impairment) perfectly fits this diagnostic pattern.

Question 104: A 45-year-old man with chronic pancreatitis has a 9-kg (20-lb) weight loss and diarrhea. Analysis of a 24-hour stool sample shows 28 g of fat. A deficiency of which of the following enzymes is the most likely cause?

• Lipase (Correct answer)
• Lactase
• Carboxypeptidase
• Lipoprotein lipase
• Amylase

Correct answer: Lipase

Chronic pancreatitis leads to exocrine pancreatic insufficiency, meaning the pancreas cannot produce sufficient digestive enzymes. The presence of significant fat in the stool (steatorrhea), along with weight loss and diarrhea, is a direct result of impaired fat digestion and absorption. Pancreatic lipase is the primary enzyme responsible for breaking down dietary fats, so its deficiency is the most likely cause of the patient's symptoms.

Question 105: A 19-year-old woman comes to the physician because of a 5-day history of increasingly severe right lower abdominal pain and bloody vaginal discharge. Her last menstrual period was 8 weeks ago. Abdominal examination shows exquisite tenderness of the right lower quadrant. A serum pregnancy test result is positive. Ultrasonography shows no gestational sac in the uterus. Which of the following is the most likely location of this patient’s fertilized egg?

• Right fallopian tube (Correct answer)
• Rectouterine pouch (of Douglas)
• Peritoneum of the right lower abdominal wall
• Cervix
• Right ovary

Correct answer: Right fallopian tube

The combination of a positive pregnancy test, absence of an intrauterine gestational sac, and symptoms of unilateral abdominal pain and vaginal bleeding in a sexually active woman strongly indicates an ectopic pregnancy. The most common location for an ectopic pregnancy is the fallopian tube, specifically the ampulla.

Question 106: A 65-year-old man undergoes colectomy for colorectal carcinoma. Pathology shows a tumor that is confined to the muscularis propria with 2 positive regional lymph nodes. What is this lesion's TNM stage?

• T2 N1 M0 (Stage III) (Correct answer)
• T2 N0 M0 (Stage II)
• T1 N0 M0 (Stage I)
• T3 N0 M0 (Stage II)

Correct answer: T2 N1 M0 (Stage III)

T2 indicates invasion into but not through the muscularis propria; N1 indicates 1-3 positive regional nodes; M0 = no distant metastasis = Stage III.

Question 107: A patient with familial hypercholesterolemia has markedly elevated LDL. The primary defect impairs which cellular process?

• HDL-mediated reverse cholesterol transport
• Secretion of VLDL from hepatocytes
• De novo cholesterol synthesis via HMG-CoA reductase
• Receptor-mediated endocytosis of LDL particles (Correct answer)

Correct answer: Receptor-mediated endocytosis of LDL particles

Familial hypercholesterolemia is caused by loss-of-function mutations in the LDL receptor, impairing endocytosis and clearance of circulating LDL.

Question 108: Which of the following post-translational modifications is most likely to be found on a cyclin B protein that is targeted for degradation?

• Ubiquitinated lysine residues (Correct answer)
• Phosphorylated tyrosine residues
• Acetylated lysine residues
• Phosphorylated serine residues
• Phosphorylated threonine residues

Correct answer: Ubiquitinated lysine residues

The degradation of cell cycle regulatory proteins, such as cyclin B, is a tightly controlled process essential for proper cell cycle progression and exit from mitosis. Proteins targeted for degradation via the ubiquitin-proteasome system are covalently tagged with multiple ubiquitin molecules, typically on lysine residues. This polyubiquitin chain serves as a signal for recognition and breakdown by the proteasome.

Question 109: A 48-year-old man has hepatic cancer that is unresponsive to standard therapy. He enrolls in a clinical study of a novel chemotherapeutic agent that, as a side effect, blocks kinesin, a component of the cellular microtubular transport system. One week later, he develops skeletal muscle weakness. An alteration in which of the following components of the neuromuscular junction is the most likely cause of the muscle weakness?

• Impaired α-motoneuron action potential conduction
• Impaired skeletal muscle action potential conduction
• A decrease in the presynaptic neuron calcium permeability
• A decrease in the number of postsynaptic neurotransmitter receptors
• A decrease in the number of presynaptic neurotransmitter vesicles (Correct answer)

Correct answer: A decrease in the number of presynaptic neurotransmitter vesicles

Kinesin is a motor protein that uses microtubules to transport vesicles, including neurotransmitter vesicles, from the neuronal cell body down the axon to the presynaptic terminal. Blocking kinesin would impair this axonal transport, leading to a reduced number of neurotransmitter vesicles available for release at the neuromuscular junction. Fewer vesicles mean less neurotransmitter release, resulting in impaired muscle contraction and weakness. The other options describe different mechanisms of neuromuscular junction dysfunction not directly related to kinesin's role in vesicle transport.

Question 110: A 15-year-old girl is brought to the physician by her mother because of a 1-year history of monthly cramps that begin 2 days before menses and last 3 days. The cramps have increased in severity during the past 6 months. She is unable to practice with her volleyball team because of the pain and typically misses 2 days of school monthly. Menarche was at the age of 12 years. Menses occur at regular 30-day intervals and last 4 days with normal flow. She has no history of serious illness and takes no medications. She has never been sexually active. Physical examination shows no abnormalities. Which of the following is the most likely cause of this patient’s pain?

• Endometrial prostaglandin production (Correct answer)
• Degenerating myoma
• Intestinal hypermobility
• Bladder wall permeability
• Escherichia coli infection

Correct answer: Endometrial prostaglandin production

This patient's symptoms are characteristic of primary dysmenorrhea, which is painful menstruation without an identifiable pelvic pathology. The pain is primarily caused by the excessive production and release of prostaglandins from the endometrium during the menstrual cycle. These prostaglandins induce strong uterine contractions, leading to uterine ischemia and the sensation of cramping pain.

Question 111: A 3-year-old girl is brought to the emergency department 2 days after the onset of fever, profuse watery diarrhea, and progressive lethargy. On arrival, she appears ill and is poorly responsive. Her temperature is 39.4°C (103°F), pulse is 180/min, respirations are 40/min, and blood pressure is 80/45 mm Hg. Examination shows poor skin turgor and cool extremities. Mucous membranes are dry. Capillary refill time is delayed. Which of the following is the most appropriate next step to decrease the risk of acute renal failure in this patient?

• Monitoring urine output
• Ceftriaxone therapy
• Vasopressor therapy
• Fluid resuscitation (Correct answer)
• Diuretic therapy

Correct answer: Fluid resuscitation

This 3-year-old girl is in hypovolemic shock due to severe dehydration from profuse watery diarrhea, evidenced by lethargy, hypotension, tachycardia, poor skin turgor, cool extremities, and delayed capillary refill. Aggressive intravenous fluid resuscitation is the most critical immediate step to restore circulating volume, improve perfusion to vital organs, and prevent acute renal failure, which is a common complication of severe dehydration.