Assistant Professor, Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy
Clinical Pharmacy Specialist (Genitourinary Malignancies), Department of Pharmacy, North Carolina Cancer Hospital, Chapel Hill, North Carolina
https://pharmacy.unc.edu/news/directory/crona/
A 35-year-old man presents to his primary care physician with a chief complaint of palpitations and occasional chest pain blood pressure record chart uk discount 50mg atenolol amex. Further questioning reveals a recent history of weight loss blood pressure juicing order atenolol 100mg free shipping, diarrhea hypertension classification jnc 7 discount 100mg atenolol free shipping, and heat intolerance heart attack racing purchase atenolol 100mg without prescription. A 12-year-old boy who recently emigrated from Nigeria presents with a six-month history of intermittent fever, fatigue, and night sweats. Biopsy of the mass shows an interspersed pattern of macrophages with sheets of lymphoblasts. This question is asking about the basic physiology behind the oxygen-hemoglobin dissociation curve, which shows how much oxygen is bound to hemoglobin at a given partial pressure of oxygen under normal conditions. Under abnormal conditions the curve can shift to the left, indicating increased affinity for oxygen, or shift to the right, indicating decreased affinity (lower percentage of bound oxygen at a given partial pressure of oxygen). Having a decreased affinity means that it may take higher partial pressures to bind four oxygen molecules to one molecule of hemoglobin, but in the periphery hemoglobin is quicker to release oxygen molecules. Therefore shifting the curve to the right would increase peripheral oxygen availability. Therefore raising partial pressure of arterial carbon dioxide, which translates into decreasing pH, in principle ought to increase peripheral oxygen availability. It maintains blood flow to the brain at the expense of the some organs and peripheral tissue. At high doses, peripheral vasoconstriction is so severe that cyanotic fingers may be seen. Therefore while norepinephrine has no direct effect on hemoglobin, it decreases peripheral oxygen availability. Higher fetal hemoglobin levels raise oxygen affinity which decreases peripheral availability. Therefore inhibiting its synthesis will increase oxygen affinity and make hemoglobin less likely to release oxygen at a given partial pressure of oxygen in the periphery. Phenoxybenzamine is a nonselective a-antagonist that will block both a1- and a2-receptors. In this patient, the administration of high-dose epinephrine (which is both an a- and a b-agonist) would result in unopposed b1- (increased heart rate, increased contractility) and b2- (vasodilation, bronchodilation) agonist effects because the a-effects of epinephrine are blocked by prior phenoxybenzamine administration. The net effect will be b-agonist effects, including an increase in heart rate and a decrease in blood pressure. Unopposed b-agonist effects will cause an increase in heart rate because b1-agonists result in increased heart rate. Unopposed b-agonist effects will cause a decrease in blood pressure because b2-agonists result in vasodilation. Unopposed b-agonist effects will cause changes in both blood pressure and heart rate. The upper-extremity hypertension and weak pedal and popliteal pulses suggest coarctation of the aorta. Coarctation of the aorta typically is a discrete narrowing of the thoracic aorta just distal to the left subclavian artery. The major clinical finding in patients with coarctation of the aorta is a difference in systolic blood pressure between the upper and lower extremities. Other common features of Turner syndrome include short stature, a webbed neck, streaked ovaries, and primary amenorrhea. These children have severe mental retardation, "rocker bottom" feet, and clenched hands (ie, flexion of fingers). Although patients with Edwards syndrome do have congenital heart disease, it generally is not associated with coarctation of the aorta. These patients have mental retardation, prominent epicanthal folds, and congenital heart disease (most often atrial septal defects). Klinefelter syndrome manifests in phenotypic males as testicular atrophy, androgenous body shape, long extremities, and gynecomastia. The x-ray shows multiple lytic "punched out" lesions in the skull, which is a classic finding for this plasma cell malignancy. Urinary protein (termed Bence-Jones proteins in this setting) is a common finding in multiple myeloma because the neoplastic plasma cells secrete an abundance of immunoglobulin pro- teins, with the light chains readily excreted. Excessive serum levels of immunoglobulin can lead to nephropathy or amyloidosis in these patients. Osteogenesis imperfecta results from a defect in the synthesis of collagen I and leaves patients susceptible to pathologic fractures. In addition to brittle bones, insufficient collagen I can lead to abnormal dentition, conductive hearing loss, and a bluish hue in the sclera. However, this disease does not first present in late adulthood, and would not be associated with lytic bone lesions. This is a description of Chvostek sign, which is a manifestation of neuromuscular hyperexcitability. This would be expected in a person with symptomatic hypocalcemia, not in a patient with hypercalcemia. Bone metastases from the prostate tend to produce dense and sclerotic osteoblastic bone lesions, rather than the lytic lesions seen on the radiograph. Moreover, one would expect an elevated alkaline phosphatase level in the setting of osteoblastic metastases. Parathyroid adenomas are a common cause of hyperparathyroidism and consequent hypercalcemia. However, alkaline phosphatase levels should be markedly elevated in hyperparathyroidism. Moreover, parathyroid neoplasms are rarely malignant, and widespread skeletal metastases would not be expected in a patient with a parathyroid adenoma. Unfortunately, many tests are performed upon patient request despite the associated risks, simply because it is less time consuming to order the test than to explain why it is unwarranted. Fibroadenomas are the most common benign breast tumors and usually occur in young women 20-35 years old. On histology, fibrosing interlobular stroma is seen around normal duct and gland structures. Fibroadenomas are frequently single, well-circumscribed, rubbery, and painless masses. They are hormone responsive during the menstrual cycle and often become hyalinized and can calcify, mimicking breast carcinomas on mammography. A stable fibroadenoma in a young woman is usually followed by ultrasonography; however, cytology is indicated if there is any doubt about malignancy or if mass is growing in size. Intraductal papillomas are benign solitary lesions that line the lactiferous ducts. These masses present in premenopausal women with serosanguinous (serous fluid and/or blood) and unilateral nipple discharge. Usually the mass undergoes cytology to rule out invasive papillary carcinoma due to the bloody discharge associated with both. These benign masses rarely undergo malignant transformation and are treated with ice packs, the cessation of breast-feeding, and tight-fitting support bras. If the mass does not subside in a couple weeks, then excision is warranted to avoid abscess formation. Paget disease of the breast is a rare manifestation of breast cancer that presents unilaterally with eczematous skin findings associated with underlying ductal carcinomas. Paget cells (cells of the underlying ductal carcinoma) are large cells with halo-like clearings. Infiltrating lobular carcinomas are identified as irregular masses on palpation or serendipitously on mammography. These cells are found in clusters or in a linear formation; the histological hallmark is a pattern of monomorphic infiltrating cells usually only one cell wide. These masses are more common in postmenopausal women and present like invasive ductal carcinoma, so they must be differentiated with excisional biopsy for cytology. Invasive ductal carcinoma (nonspecific type) is the most common breast mass in older women. On palpation, they are usually firm, irregular, fixed masses; on mammography, they appear as multiple small calcifications. A decrease in free radical production because of this enzyme deficiency renders host neutrophils sensitive to catalase-producing organisms (notably Staphylococcus aureus, Candida albicans, Aspergillus flavus, Escherichia coli, and Pseudomonas aeruginosa), because catalase breaks down free radicals.
Kidney imaging may show cortical or parapelvic cysts pulse pressure greater than 50 buy 100 mg atenolol amex, the cause of which is unknown blood pressure medication addiction generic 50 mg atenolol visa. Similar to other nephropathies blood pressure quickly lower best 50mg atenolol, proteinuria and hypertension are also associated with more rapid decline in kidney function blood pressure changes buy atenolol 100mg without a prescription. In patients with an established diagnosis of Fabry disease, a routine kidney biopsy is not mandatory. Annual monitoring should include measurement of serum creatinine and urinary albumin- or protein-to-creatinine ratio. In conventional light microscopy on formalin-fixed and paraffin-embedded material, these inclusions appear empty, because their content is removed during processing. Fixation with osmium and embedding in epoxy resins retains the stored material that can easily be visualized by 10707 1373 1120 5268 5094 7446 7269 8412 8321 10292 11266 10131 10978 10510 either light microscopy on thin section with Toluidin blue or Methylene blue staining and electron microscopy. The lipid content of the inclusions is sudanophilic and stains with oil red O on frozen section. Kidney biopsy is therefore considered a valuable instrument in the baseline assessment of Fabry nephropathy, and a validated scoring sheet has been Exons 1 2 3 4 5 6 7 A Stroke Hearing Loss Corneal whorling Left ventricular hypertrophy Pulmonary obstruction Kidney failure Abdominal pain Diarrhea Nausea B Figure 44. The upper scheme shows the exon position numbering according to the GenBank database entry X14448. The structure of the human -galactosidase A dimer is shown in ribbon representation. The ribbon is colored from blue to red as the polypeptide goes from N- to C-terminus. Each monomer in the homodimer contains two domains, a (/)8 barrel containing the active site (blue to yellow) plus a C terminal antiparallel domain (yellow to red). These mutations include 438 missense and nonsense point mutations, 102 small deletions and 32 small insertions, 9 small indels, 16 gross deletions and 2 gross insertions, as well as 5 complex rearrangements and 34 mutations that affect splice sites. A, Light microsocopy of formalin-fixed and paraffin-embedded material shows "foamy" podocytes (arrows) resulting from numerous empty cytoplasmic vacuoles (periodic acid-Schiff). B, Toluidin blue on Epon-embedded thin section), and they correspond by electron microscopy to lamellated membrane inclusion bodies with either "zebroid" (C) or "myelin-like" (D) appearance in secondary lysosomes. These consist of concentric "myelin-like" rings, or have a striped "zebroid" appearance. The most debilitating early symptom, often starting in childhood, is chronic pain; this is typically triggered by vigorous exercise and temperature changes. Pain (and depression) management agents include gabapentin, carbamazepine, phenytoin, amitriptyline, and other antidepressants. The index case was diagnosed by a nationwide case-finding study among Austrian dialysis patients. His mother and the two daughters carry the same mutation and were asymptomatic at the time of screening. Acroparesthesia or neuropathic pain in hands or feet beginning in later childhood, precipitated by illness, fever, exercise, emotional stress, or exposure to heat 2. This may be the only clinical manifestation of Fabry disease in patients of either gender with variants of classical Fabry disease. The 5-year survival after kidney transplantation is also lower than that of controls. However, Fabry nephropathy does not recur in the allograft, and transplanted Fabry patients appear to have better overall outcomes than those maintained on dialysis. Therefore, kidney transplantation should be recommended as a first choice therapy for patients with Fabry disease. It can be considered for every adult male patient, for symptomatic boys, and for symptomatic women. Two preparations are currently available, with other products in clinical development. In Elstein D, Altarescu G, Beck M, editors: Fabry disease, Dordrecht, Heidelberg, London, New York, 2010, Springer, pp. Fabrazyme is the only currently available enzyme replacement in the United States. Side effects of enzyme replacement therapy include fever, rigors, and chills, typically mild to moderate in nature. These occur in more than half of the patients during the first months of treatment. Infusion related reactions may be due to IgG or IgE antibodies that can be detected in several patients. In case of reactions, the infusion rate should be be decreased or stopped, and the administration of antihistamines and/or corticosteroids should be considered. Some patients need premedication with antihistamines, paracetamol/acetaminophen, or corticosteroids. In patients receiving maintenance dialysis therapy, the infusion can be administered during dialysis treatment. The clinical effect of both products was examined in two small pivotal trials, a few controlled studies, and numerous uncontrolled studies and registry reports. The primary endpoint was neuropathic pain that improved during therapy with Replagal as assessed by a pain questionnaire. After 20 weeks of treatment, 20 of the 29 patients (69%) in the Agalsidase B group had no microvascular endothelial Gb3 deposits, as compared to no clearance in the placebo group. Among secondary endpoints, there was no difference on pain between active treatment and placebo. A per-protocol analysis, adjusted for baseline proteinuria, however, suggested an effect of Agalsidase B as compared to placebo. Uncontrolled studies suggested stabilization or even improvement of renal and cardiac disease manifestations during enzyme replacement therapy in many patients. Quality of life, gastrointestinal symptoms, hypohydrosis, pulmonary obstruction, and other clinical symptoms also showed improvement. Kidney function, proteinuria, and blood pressure are important predictors of the renal response to enzyme replacement therapy. In a recent analysis of 213 treated patients (Agalsidase B for at least 2 years) enrolled in the Fabry Registry, a higher urinary protein level, poorer initial kidney function, and delayed initiation of enzyme replacement therapy after the onset of symptoms were strong predictors of kidney disease progression in men. Patients with 24-hour protein excretion greater than 1 g/24 h had poorer kidney function at baseline and follow-up compared with patients with protein excretion of 500 to 1000 mg/24 h or less than 500 mg/24 h. Kidney function was worse in patients with baseline hypertension, and there was a more rapid annual decline compared with normotensive patients. Taken together, these data clearly show that Agalsidase A or Agalsidase B cannot halt kidney disease progression in many patients. Thus, novel therapeutic strategies are needed to improve outcomes in patients with Fabry disease. These include higher frequency and other routes of administration of the enzyme, and the combination or monotherapy with pharmacologic chaperones. Taken together, these data suggest an important clinical potential for this new therapeutic tool, alone or in combination with enzyme replacement therapy. Feriozzi S, Torras J, Cybulla M, et al: the effectiveness of long-term agalsidase alfa therapy in the treatment of Fabry nephropathy, Clin J Am Soc Nephrol 7:60-69, 2012. Schwarting A, Dehout F, Feriozzi S, et al: Enzyme replacement therapy and renal function in 201 patients with Fabry disease, Clin Nephrol 66:77-84, 2006. Schiffmann R, Ries M, Timmons M, et al: Long-term therapy with agalsidase alfa for Fabry disease: safety and effects on renal function in a home infusion setting, Nephrol Dial Transplant 21:345-354, 2006. In Elstein D, Altarescu G, Beck M, editors: Fabry disease, 2010, Springer, pp 153-162. West M, Nicholls K, Mehta A, et al: Agalsidase alfa and kidney dysfunction in Fabry disease, J Am Soc Nephrol 20:1132-1139, 2009. All forms of progressive kidney disease eventually result in chronic and progressive interstitial fibrosis. One hypothesis concerning immune recognition of the interstitium suggests that portions of infectious particles or drug molecules may cross-react with or alter endogenous renal antigens. An immune response directed against these inciting agents would therefore also target the interstitium. Primary interstitial nephropathies make up a diverse group of diseases that elicit interstitial inflammation associated with renal tubular cell damage. Traditionally, interstitial nephritis has been classified morphologically and clinically into acute and chronic forms.
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Typically hypertension and pregnancy generic atenolol 100mg on-line, hematuria is unilateral and occurs nearly four times more often from the left kidney heart attack indigestion order atenolol 100mg amex. The longer course and higher venous pressures of the left renal vein as it traverses between the aorta and superior mesenteric artery likely lead to this phenomenon blood pressure young living buy discount atenolol 100mg online. Although bleeding is typically benign and self-limited blood pressure chart sheet 100 mg atenolol otc, massive hemorrhage can occur and potentially be life threatening. Treatment consists of conservative management with bed rest and maintenance of high urine output to prevent clots. Alkalinization of the urine may help by raising medullary pH, thereby reducing sickling; however, no proven benefit has been shown in studies. Intravenous fluids may be employed to ensure high urine flow, but must be used with caution in patients at risk for congestive heart failure or acute chest syndrome. Diuretics can also be used to increase urine flow rates, but care must be taken to avoid volume depletion. Early in life, this defect is partially reversible following blood transfusions that rapidly increase normal hemoglobin A (HbA) and reduce sickling in the vasa recta. However, impaired urinary concentration becomes fixed later in life (as early as age 15) and no longer improves with transfusion. Pooling of contrast material within multiple papillae bilaterally (open arrow) is consistent with papillary necrosis. Filling defect within left renal pelvis (solid arrow) was shown to represent blood clot at ureteroscopy. In patients who are refractory to medical therapy, invasive intervention may be necessary. If a source of bleeding can be localized via imaging, attempts at percutaneous embolization have been attempted. In all patients presenting with hematuria, and particularly in those with persistent or massive hematuria, alternative causes should be considered, including acquired or hereditary bleeding disorders or abnormalities such as nephrolithiasis, polycystic kidney disease, or renal medullary carcinoma (see next sections). Repetitive ischemic injuries to the tubules are postulated to drive the development of this lesion. The typical presentation is gross hematuria accompanied by lumbar pain or abdominal masses, although malignant constitutional symptoms of weight loss, fevers, and fatigue may be present. Regrettably, this malignancy is usually metastatic at diagnosis, with survival of only 6 to 12 months. Hyperkalemia may accompany this; however, this is rare without significant potassium ingestion or medications that interfere with potassium handling. The inability of the damaged distal nephron to excrete ammonium and titratable acids, as well as an inability to respond to aldosterone, lead to these findings. If necessary, treatment with potassium restriction, sodium bicarbonate, and loop diuretics can be effective. The aforementioned abnormalities generally indicate impaired distal tubule secretory function. Sodium reabsorption is increased, leading to less urinary excretion, as well as a relative resistance to loop diuretics. Accompanying this increase in sodium reabsorption is an enhancement of proximal phosphate reabsorption that may cause hyperphosphatemia in settings of increased phosphorus loads (hemolysis, rhabdomyolysis). Additionally, uric acid secretion is increased, perhaps as an adaptive mechanism to the increased uric acid load from chronic hemolysis. Although often accompanied by hematuria, a similar proportion of patients may be asymptomatic. With severe sickling in the vasa recta, the renal papillae that depend on these vessels can undergo focal, repetitive infarcts leading to necrosis (Figure 40. If hematuria is present, as described earlier, patients should undergo an evaluation for other potential causes, including kidney masses or nephrolithiasis. Treatment, as with hematuria, is generally supportive, employing similar measures. If significant sloughing occurs, necrotic and thrombotic material may lead to ureteral obstruction, which can be diagnosed by urography and relieved by stenting. The nephrotic syndrome itself is fairly rare, but it portends a poor kidney prognosis. Lower hemoglobin levels and pulmonary hypertension may be associated with the development of albuminuria. As repetitive sickling occurs and interstitial fibrosis leads to dropout of affected nephrons, hyperfiltration is further accentuated in the remaining glomeruli. Additionally, evidence suggests endothelial dysfunction from both direct injury related to sickling and the release of free heme during hemolysis. These effects seem to be independent of any blood pressure lowering and are likely related to reduction of glomerular capillary hypertension. Although specific guidelines do not exist, patients should be screened periodically for albuminuria, and renin-angiotensin blockade should be initiated if albuminuria is detected. The mechanism of action is not completely understood, but it is in part due to the ability of hydroxyurea to induce HbF production and thereby reduce the overall concentration of hemoglobin S. Hydroxyurea may also affect the synthesis of nitric oxide, and has other beneficial effects. However, a recently published large study of its use in infants failed to demonstrate prevention of hyperfiltration, although this study may not have been of long enough duration or utilized a population old enough to demonstrate a potential benefit. Generally, a maximum achieved hemoglobin level of 10 mg/dL is recommended to avoid precipitation of vasoocclusive crises. Iron stores should be maintained to maximize erythropoiesis in those not receiving chronic transfusions, although care must be taken to avoid iron overload in this susceptible population. Various explanations for this finding have been posited, including relative volume depletion and reduced systemic vascular resistance. Some suggest avoidance of diuretics given their predisposition to volume depletion, which can induce a pain crisis. Guasch A, Navarrete J, Nass K, et al: Glomerular involvement in adults with sickle cell hemoglobinopathies: Prevalence and clinical correlates of progressive renal failure, J Am Soc Nephrol 17:2228-2235, 2006. Hematology / the Education Program of the American Society of Hematology Education Program, Am Soc Hematol Educ Program 418-422, 2010. In Programs and abstracts of the 42nd Annual Meeting of the American Society of Nephrology; San Diego: 2009, p 7. Early referral to a nephrologist is particularly important for this population of patients. Notably, though, patient survival at 10 years for those receiving kidney transplants is far greater than those treated with dialysis alone (56% vs. Hydroxyurea and exchange transfusion have been used in the posttransplant period, and simultaneous bone marrow transplantation could be curative of the disease as a whole. Again, the severity of the concentrating defect seems to be modulated by the co-inheritance of -thalassemia. Chapman Significant advances have been made in understanding the genetics and molecular pathogenesis of inherited cystic disorders of the kidney. Final common pathways regarding the formation and development of cysts are being elucidated. Most renal cysts develop because of abnormal function of the primary cilium that resides in all epithelial cells. Recently developed molecularly targeted therapies offer hope for improved outcome or cure of these disorders. It localizes to the endoplasmic reticulum, plasma membrane, primary cilium, centrosome, and mitotic spindles in dividing cells. Polycystin-1 and 2 are colocalized in the primary cilium of renal epithelial cells, which functions as a mechanical sensor. Primary cilia create transmembrane calcium current in the presence of stretch or luminal flow. Polycystin-1 and 2 contribute to ciliary function, and the physical interaction between polycystin-1 and 2 is required for a membrane calcium channel to operate properly. Normal polycystin function increases intracellular calcium, which initiates a signaling cascade leading to vesicle fusion and a change in gene transcription. This chloride-rich fluid secretion is a critical component of cystogenesis, enabling expansion of cysts even after they detach from their parent nephron.
Bartter syndrome has three variants hypertensive emergency buy discount atenolol 100 mg on line, each affecting the sodium-potassium-chloride pump and each resulting in a different defective channel in the thick ascending limb of the loop of Henle arteria hepatica comun order atenolol 100 mg overnight delivery, the site at which furosemide arteria plantaris medialis discount atenolol 50 mg mastercard, a loop diuretic blood pressure upon waking buy 100 mg atenolol with amex, acts. Acetazolamide acts at the proximal convoluted tubule, inhibiting carbonic anhydrase. Acetazolamide can result in type 2 renal tubular acidosis, but not Bartter syndrome. Metabolic derangements seen with this drug include hypokalemic metabolic acidosis, hyponatremia, hyperglycemia, hyperlipidemia, hyperuricemia, and hypercalcemia. Spironolactone is a potassium-sparing diuretic that acts as a competitive aldosterone receptor antagonist in the cortical collecting tubule. Adverse effects include hyperkalemia and antiandrogenic effects, such as gynecomastia. Triamterene is a potassium-sparing diuretic that blocks sodium channels in the cortical collecting tubule. Although this disease can affect any part of the body (including the heart, lungs, brain, joints, and eyes), the most common presenting feature of Whipple disease is diarrhea due to malabsorption. The most common disaccharidase deficiency is lactase deficiency, which results in lactose intolerance. In patients with lactose intolerance, drinking milk can cause abdominal pain, diarrhea, and increased flatulence. Similar to celiac sprue, tropical sprue is characterized by autoantibodies to gluten (gliadin) in wheat and other grains. Histologic examination in celiac sprue reveals villus flattening and lymphocytic infiltrate. Antigliadin, antiendomysial, and anti-tissue transglutaminase antibodies are present, resulting in malabsorption. The three classic findings associated with Graves disease are hyperthyroidism, ophthalmopathy (exophthalmos), and dermopathy/pretibial myxedema (ie, nonpitting edema on the anterior surface of both legs, with overlying skin that is dry and waxy and may have several diffuse, slightly pigmented papules). They work by blocking tyrosine iodination (also known as organification) and coupling. Propylthiouracil also decreases peripheral conversion of thyronine to triiodothyronine (T3). Active absorption of iodide is known as "trapping" and is the first step in thyroid hormone synthesis. Alcoholic patients often have reduced intake of calories other than from alcohol and become deficient in various nutrients, among them vitamin B1 (thiamine). Without it, cells are in a low-energy state that will eventually damage those cells with highenergy requirements (neurons and myocardium). Wernicke encephalopathy is an acute syndrome that is reversible with thiamine administration; it is characterized by mental status changes (disorientation, confusion, inattention), ophthalmoplegia, ataxia, and nystagmus. Additionally, peripheral neuropathy (dry beriberi) or dilated cardiomyopathy (wet beriberi) may develop, as in this patient. A transesophageal echocardiogram allows for assessment of the extent of the cardiomyopathy. Coagulation studies will most likely reveal prolonged times in this patient (ie, the patient is anticoagulated). Although compartment syndrome presents with edematous tissues, it is not associated with neurologic symptoms such as confusion and confabulation. Furthermore, the question stem does not describe any possible historical clues for compartment syndrome to develop (such as recent trauma). The patient is too old for an inherited clotting disorder to appear (usually occurs before age 40), and no predisposing factors are listed in the question stem (eg, recent surgery, cancer, oral contraceptives). In fact, many alcoholics are somewhat anticoagulated, as a damaged liver produces fewer clotting factors. Benign lesions are flat and have smooth borders, unlike malignant lesions, which may protrude into the lumen and have irregular borders. The patient is suffering from hyperparathyroidism secondary to renal disease, also known as renal osteodystrophy. As the glomerular filtration rate decreases, excretion of phosphate also decreases, leading to hyperphosphatemia. The hypocalcemia in this patient is demonstrated as a positive Chvostek sign, in which tapping on the hyperexcitable facial nerve causes temporary facial muscle spasms. This set of lab values is characteristic of a patient with primary hyperparathyroidism. Critical points to consider in this question are first, that the patient is a nonsmoker; second, that the lesion is localized peripherally (subpleural mass); and third, that the patient is a woman. About 95% of all lung cancers can be classified into one of two categories: small cell lung cancers make up 13%, and non-small cell lung cancers (consisting of adenocarcinoma, squamous cell carcinomas, and other histologic types) make up the rest. Adenocarcinoma is the most prevalent type of lung cancer, representing 38% of all diagnosed cases. Relative to squamous cell carcinoma (the second most prevalent subtype), adenocarcinoma is more often seen in nonsmokers than in smokers (62% vs 18%), and more often seen in women than in men irrespective of smoking status. Because adenocarcinomas are typically peripherally located (75%), they often are more amenable to surgical removal than other tumor types, although the success of treatment depends more on the stage of the tumor than the type. Carcinoid tumors are found in major bronchi and may cause carcinoid syndrome (flushing due to excessive his- tamine release). Although metastases from other organs arise more commonly than primary lung tumors, they are most often multifocal, not a single peripheral nodule. Metastases to lung principally arise from primary tumors of the breast, colon, and kidney. Small cell carcinoma of the lung is an undifferentiated tumor usually present in a central location. Small cell lung cancer is rarely resectable and is most often treated with combination chemotherapy and radiation. Squamous cell carcinoma of the lung often presents as a centrally located hilar mass. This lung cancer subtype is more common in men, and it exhibits the strongest link to smoking. A 45-year-old man presents to his physician complaining of a five-month history of occasional burning mid-epigastric pain that improves when he eats food. He denies any history of recent travel or excessive use of nonsteroidal anti-inflammatory drugs. She says her husband has noticed that her eyes have recently been "moving out of sync" with one another. A lesion of the right medial longitudinal fasciculus would result in which combination of eye movements The patient is not diabetic, hypertensive, or dyslipidemic, and all of his family members are healthy. After a cesarean section delivery, the newborn baby is noted to have signs of cyanosis, tachypnea, and dyspnea. Which of the following is a characteristic of the substance that is insufficient in the baby A 30-year-old African-American man presents to his primary care physician complaining of dizziness and lethargy. About a week ago he completed a 14-day course of antibiotics prescribed by his doctor for bacterial sinusitis. He is normally in good health, eats a diet full of fruits and vegetables, and exercises daily. He denies any changes in his diet and has not experienced any gastrointestinal distress, although he admits to tea-colored urine over the past three-four days. His blood pressure is 100/70 mm Hg, pulse is 110/min, and respirations are 19/ min. On the second hospital day, he developed extreme pulmonary edema and hypotension before he died. His family says that he had recently gone hiking and caving in an area heavily populated with rodents. A 33-year-old refugee from Sudan presents to the emergency department with a history of increasing fever and fatigue over the past six months. Intravenous administration of drug X to an anesthetized animal produces an increase in its systolic blood pressure.
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