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By: A. Kadok, M.B. B.CH., M.B.B.Ch., Ph.D.

Clinical Director, Donald and Barbara School of Medicine at Hofstra/Northwell

Their clinical features are predominant in males medications covered by medicare buy generic oxybutynin 5mg on line, postprandial neuroglycopenia medications for bipolar buy oxybutynin with paypal, negative prolonged supervised foci; negative radiologic localization studies medications 1-z buy oxybutynin no prescription, positive selective arterial calcium stimulation test, and relief of symptoms with gradient guided partial pancreatectomy. Insulin factitial hypoglycemia usually is manifested by neuroglycopenic symptoms that occur erratically. This disorder is observed more often in women, usually those in a health-related occupation. Once confronted with the diagnosis, about half of the patients admit to self-abuse and most cease this activity. Insulin autoimmune hypoglycemia may be very difficult to distinguish from insulin factitial hypoglycemia because of similar biochemical features. Mutations in the beta-cell sulfonylurea receptor gene, glutamate dehydrogenase gene, and glucokinase gene have been reported to cause hyperinsulinemic hypoglycemia, primarily at an early age and often in a familial pattern. Islet cell tumors are commonly referred to as either "functioning" or "non-functioning. Functioning tumors generally present with symptoms relating to the hormone(s) being secreted whereas non-functioning tumors generally present as a pancreatic mass or as a metastasis. Non-functioning tumors tend to be larger and more advanced at the time of diagnosis. Functioning islet cell tumors are commonly associated with one of five widely recognized syndromes (Table 243-4) (Table Not Available). However, a number of additional symptoms also can occur because these tumors frequently secrete more than one hormone. Islet cell tumors are either sporadic or can occur in association with other known genetic syndromes such as multiple endocrine neoplasia type 1. Sporadic tumors occur at any age but most commonly are detected between 40 and 60 years of age. The diagnosis can be confirmed by obtaining tissue during surgical resection or by means of a needle biopsy. With the exception perhaps of insulinomas, the optimal treatment of islet cell tumors is currently not known because their rarity has made the conduct of randomized therapeutic trials extremely difficult. Furthermore, in the absence of metastases, there are no reliable histologic criteria that can distinguish benign from malignant lesions. Islet cell tumors most commonly metastasize to the liver and adjacent lymph nodes. Therefore, many clinicians would recommend surgery if the pancreatic tumor is resectable and if the extent of metastatic disease (if present) is limited. Treatment with chemotherapeutic agents such as streptozotocin (alone or in combination with 5-fluorouracil), doxorubicin, dacarbazine or interferon-alpha also may improve symptoms and, in some instances, perhaps improve survival. Insulin-Secreting Tumors Insulinomas are the most common type of islet cell tumor. As discussed earlier in this chapter, these tumors cause hypoglycemia, are typically small, and are usually benign. Gastrin-Secreting Tumors Gastrin-secreting tumors are the second most common type of islet cell tumor. When untreated, these tumors are associated with high rates of gastric acid secretion and intractable peptic ulcer disease. This group of symptoms is usually referred to as the Zollinger-Ellison syndrome, which is discussed in detail in Chapter 130. Glucagon-Producing Tumors Glucagon is a 3500-kd polypeptide that is primarily secreted by the alpha cells of the pancreas. Glucagon stimulates glycogenolysis and gluconeogenesis, increases ketogenesis, and enhances hepatic amino acid uptake and oxidation. This rash typically begins as small erythematous lesions involving the lower extremities and perineal and perioral regions. The lesions may take the form of pustules or blisters, which frequently crust and merge. It is frequently accompanied by weight loss, diabetes mellitus, stomatitis, and diarrhea.

Observations have included diffuse polyarthralgias medicine used during the civil war discount oxybutynin online amex, an arthritis ranging from monarticular to treatment naive purchase 5mg oxybutynin oligoarticular medications prednisone discount 2.5 mg oxybutynin, and a rheumatoid arthritis-like picture with polyarthritis involving the wrists, metacarpophalangeal and proximal interphalangeal joints, knees, ankles, and other large or small joints. Vasculitis is responsible for conjunctivitis, scleritis-episcleritis, uveitis, retinal vasculitis, and corneoscleral ulceration. Granulomatous mass lesions contribute to proptosis, orbital masses, optic nerve compression, diplopia, and nasal lacrimal duct obstruction. Cutaneous involvement is most typically seen as palpable purpura, predominantly in the lower extremities, but it may occur in the upper extremities and over bony prominences. Neurologic involvement is most typical with mononeuritis multiplex and footdrop and/or wristdrop, with patchy sensory and/or motor abnormalities. Headaches, hypothalamic or pituitary disease with clinical diabetes insipidus, and cerebral or subarachnoid hemorrhage have been reported infrequently. Cardiovascular manifestations include pericarditis, pericardial effusions, and rarely, coronary vasculitis, myocarditis, congestive heart failure (other than observed secondary to acute renal failure), valvular abnormalities, and arrhythmias. The diagnosis is based on supportive clinical, pathologic, and laboratory confirmation. The diagnosis should be strongly suspected when a patient has multisystem illness involving upper and/or lower respiratory tract disease, glomerulonephritis, and vasculitis in any organ system. Localized disease may lead the clinician to entertain biopsy of other tissues, and thus knowledge of the array of pathologic findings in other organ systems is necessary. A typical laboratory profile included normocytic normochromic anemia, unelevated erythrocyte sedimentation rate, leukocytosis, and positive rheumatoid factor in 30 to 40% of patients, with or without urine sediment abnormalities or elevated serum creatinine. When the process is early and/or limited to the upper airway or kidney, the diagnosis is clinically challenging. Destructive upper airway disease needs to be differentiated from infection such as fungal, mycobacterial, staphylococcal, or syphilitic; substance abuse (particularly cocaine); malignancy (particularly T-cell lymphoma and squamous cell carcinoma); or rarely, self-mutilating trauma. In the past, idiopathic midline granuloma or idiopathic midline destructive disease was included in the differential diagnosis. Cyclophosphamide therapy is started at a dose of 1 to 2 mg/kg/day, with initially weekly monitoring of complete blood counts to keep the total white count above 3. The dose is adjusted according to blood counts, particularly as corticosteroid use is tapered. This drug or alternative therapy is reinstituted in the case of recurrence or relapse. Complications include hemorrhagic cystitis (and thus patients should be instructed to drink at least 1. Corticosteroids are used at the time of diagnosis for severe disease, initially at 1 mg/kg/day (may be used in divided dose, intravenous methylprednisolone for fulminant disease, followed by consolidation to daily or alternate-day therapy). Prednisone equivalent doses of 60 mg/day are then tapered to alternate-day therapy over 1 month and then to the lowest possible level to control upper airway and/or musculoskeletal symptoms, preferably discontinuing use of this drug by 3 to 6 months. However, relapses occur in at least 50% of those achieving remission at any time from several months to 15 to 20 years after stopping cytotoxic therapy. Weekly low-dose (15 to 25 mg) oral or intramuscular methotrexate has provided hope and, because of experience in the management of rheumatoid arthritis, may provide a less toxic alternative to cyclophosphamide in patients who relapse, particularly with significant upper airway disease. Azathioprine, pulse monthly cyclophosphamide, intravenous immunoglobulin, cyclosporine, and immune modulators have all been used in individual cases. Because of the relative infrequency of the disease, controlled, double-blind studies have not yet been performed. Antibiotic therapy has a role, but at present it is considered adjunctive, not primary therapy. Because of necrotic upper airway tissue, staphylococcal and other infections are quite common and could be part of the "chicken and egg" perpetuation of this condition. Careful diagnosis, thoughtful management, and close follow-up are necessary for optimal outcome. Hunder Polymyalgia rheumatica and giant cell arteritis are common rheumatic diseases of middle-aged and older persons. Although the etiology of these conditions is unknown, it is clear that they are closely related. Recent studies suggest that a single agent causes both conditions and that host and other unknown factors determine whether one or both processes will develop.

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Patients with slower or inactive bleeding may be evaluated by endoscopy in a "semi-elective" manner (usually within 12-20 hours) treatment 5th disease purchase oxybutynin 5mg on-line, but a case can be made to medications vitamins cheapest oxybutynin perform endoscopy very early even in these stable patients (perhaps in the emergency department itself) to symptoms 9f diabetes discount oxybutynin 2.5mg on line allow triage decisions to be made more confidently. Most bleeding from upper gastrointestinal lesions can be effectively controlled endoscopically. The endoscopist considers factors such as age (older patients have a higher risk of rebleeding) and the severity of the initial hemorrhage (which has a direct correlation with the risk of rebleeding) in addition to the appearance of the lesion when determining the need for endoscopic therapy. Non-variceal bleeding vessels can be treated with a variety of means including injections of various substances (epinephrine, saline, sclerosants) or thermal coagulation (laser or electrocautery). In the United States, the most popular approach to a bleeding peptic ulcer lesion is a combination of injection with dilute epinephrine and electrocoagulation. Initial hemostasis can be achieved in 90% or more of cases; rebleeding, which may recur in up to 20% of cases, will respond about half of the time to a second endoscopic procedure. Patients who continue to bleed (typically patients with large ulcers in the posterior wall of the duodenal bulb) are usually managed angiographically (with embolization of the bleeding vessel) or surgically. Variceal bleeding is also effectively managed endoscopically, with a similar success rate as with bleeding ulcers (Color Plate 2 A). Increasingly, patients who do not respond to endoscopic treatment are then considered candidates for a transjugular intrahepatic portosystemic shunt; traditional shunt surgery for bleeding varices is rarely performed. Even if initial endoscopic hemostasis is successful, long-term prevention of rebleeding requires a program of ongoing endoscopic sessions until variceal obliteration is complete. Ligation is the preferred approach in this setting because it is associated with fewer side effects. The most common cause of acute lower gastrointestinal bleeding is angiodysplasia, followed by diverticulosis, neoplasms, and colitis. In about 10% of patients presenting with hematochezia, a small bowel lesion may be responsible. In contrast to upper gastrointestinal bleeding, there is no single best test for acute lower gastrointestinal bleeding (see. In young patients (<40 years) with minor bleeding, features that are highly suggestive of anorectal origin. Conversely, patients presenting with hemodynamic compromise may need an upper endoscopy first to exclude a lesion in the upper gastrointestinal tract (typically post-pyloric) that is bleeding so briskly that it presents as hematochezia (which may be seen in 10% or more of acute upper gastrointestinal bleeding). Colonoscopy has traditionally been recommended after bleeding has slowed or stopped and the patient has been given an adequate bowel purge. However, a disadvantage of delaying endoscopy is that when a pathologic lesion such as an arteriovenous malformation (Color Plate 2 F) or diverticulum is found, it may be impossible to implicate it confidently as the site Figure 122-1 Endoscopic variceal ligation technique. A, the endoscope, with attached ligating device, is brought into contact with a varix just above the gastroesophageal junction. B, Suction is applied, drawing the varix-containing mucosa into the dead space created at the end of the endoscope by the ligating device. Some experts therefore recommend an urgent diagnostic endoscopy with little or no preparation for acute lower gastrointestinal hemorrhages and have reported success rates of 50%. Most standard fecal occult blood tests will detect blood loss of 10 mL/day or more. Therefore, even if this test is negative, patients with iron-deficiency anemia and no other obvious source of blood loss should always undergo aggressive gastrointestinal evaluation, which will uncover a gastrointestinal lesion in the majority of cases. Although most lesions that cause overt gastrointestinal bleeding can also cause occult blood loss, occult bleeding should almost never be ascribed to diverticulosis or hemorrhoids. Endoscopy is always preferable to radiographic studies for evaluation of occult blood loss or iron-deficiency anemia because of its ability to detect flat lesions, particularly vascular malformations, which may be found in 6% or more of patients. If both upper and lower endoscopy are negative, a small bowel radiographic series to look for gross lesions often completes the evaluation. However, if the patient continues to have symptomatic bleeding, enteroscopy (the use of a very long upper endoscope to intubate the small bowel) may be helpful to detect small bowel angiomata. Colonoscopy is the most accurate test for detecting mass lesions of the large bowel that are suspected on clinical or radiologic grounds. However, the greatest impact of endoscopy on colorectal neoplasia may be in the area of screening and prevention. There is good evidence that a strategy of an annual fecal occult blood test followed (if positive) with a colonoscopy and polyp removal significantly reduces mortality from colorectal cancer by up to 33% in patients at average risk for colon cancer. The second popular form of screening is sigmoidoscopy with a 60-cm scope that should detect 40 to 60% of all adenomas in the colon. Three case-control studies have shown an almost two-thirds reduction in mortality from cancers within reach of the sigmoidoscope compared with matched controls.

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The most common cause of hemoptysis is pneumonia or pulmonary infection medicine of the prophet discount 5 mg oxybutynin otc, including bronchiectasis (see Chapter 77) symptoms celiac disease buy oxybutynin 2.5 mg on-line. Bloody streaking of purulent sputum occurs during pneumonia or severe bronchitis and subsides as the infection is treated symptoms viral infection discount oxybutynin online visa. The sudden appearance of hemoptysis without other cause must be considered a possible manifestation of lung tumor, either benign or malignant. A pulmonary embolism that leads to pulmonary infarction almost always results in hemoptysis (see Chapter 84); it is usually associated with a pulmonary infiltration as a manifestation of infarction, which occasionally leads to a cavity in the lung parenchyma. Hemoptysis is not uncommon in cystic fibrosis of the lung and can be severe and even life-threatening. A certain proportion of patients have sudden and usually mild hemoptysis for which no cause can be found; such episodes may result from a ruptured blood vessel or varix in the bronchial mucosa, and clotting parameters should be checked. Mild hemoptysis also results from coughing stimulated by blood from the oropharynx; comprehensive oropharyngeal evaluation is diagnostic (see Chapter 515). Bronchopulmonary aspergillosis or an aspergilloma can cause persistent hemoptysis, while an arteriovenous malformation can cause sudden, life-threatening hemoptysis. A solitary pulmonary nodule on a chest radiograph, especially if it is new, poses the possibility of a malignancy and requires immediate diagnostic evaluation. The presence of calcification in at least 10 to 20% of the nodule near its center is the most reliable indicator of a benign lesion. However calcification of a solitary nodule is not specific for benign disease, as a cancer can develop within a scar or granuloma. A thorough review and analysis of the relationship of pulmonary symptoms to clinical and physiologic abnormalities in a range of pulmonary disorders. An informative review of the diagnostic role of positron emission tomography in relation to other tumor imaging modalities. Approach to the clinical and radiographic evaluation of patients with common pulmonary syndromes. A thorough discussion of the use of history, physical examination, and radiologic findings for differential diagnosis of lung diseases. In addition, the respiratory system carries out a large number of other ventilatory-related and nonventilatory functions. The complex effects of lung structure on its gas exchange and nonventilatory functions are critical to understanding how the lung responds to both intrapulmonary and systemic diseases. The nasopharynx plays a critical role in humidifying inhaled gases and in clearing particles and reactive substances contained in those gases. In addition to contributing to the senses of smell and taste, the nasopharynx removes a large fraction of inhaled particles and reactive gases. Turbulent gas flow past the nasal turbinates and the right-angle turn at the posterior pharynx cause impaction of most large particles before inhaled gas enters the trachea. In addition, very highly soluble or reactive gases may be almost completely removed by the nasopharynx. Lymphoid tissue at the posterior pharynx plays a role in immune processing at this critical junction of the body with its external environment. The posterior portion of the trachea, representing the membranous portion or open part of the cartilaginous rings, contains the trachealis muscle. The trachea divides into two main-stem bronchi, which then rapidly divide in an irregular dichotomous pattern into progressively smaller bronchi. Cartilaginous support surrounding or partly surrounding bronchi continues for a number of generations, at which point the airways are termed bronchioles. As the size of the cartilage decreases in smaller bronchi, the relative mass of smooth muscle becomes more prominent, and these medium-sized bronchi can be a significant site of bronchoconstriction. Smooth muscle becomes more scarce, as it extends into the bronchioles and is virtually absent from terminal bronchioles. The shortest path from the trachea to a terminal bronchiole involves approximately seven divisions and has a total length of 7 to 8 cm. The longest pathway would encounter approximately 25 branch divisions and have a total length of more than 22 cm.

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