Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary pulmonary hypertension is usually considered a disease of younger adults. We reviewed the natural course of primary pulmonary hypertension in patients aged 65 years or greater. During an 8-year period, 63 elderly patients were discharged from our hospital with a diagnosis of pulmonary hypertension. In eight instances, an elevated mean pulmonary arterial pressure (greater than 25 mm Hg) could not be explained by secondary causes. These elderly patients with primary pulmonary hypertension had symptoms common to younger patients with this disease, including dyspnea (eight patients), chest pain (five), pedal edema (four), and fatigue (one). In all but one patient, the initial diagnosis was incorrect, and the patients were thought to have more common diseases of the elderly that cause similar symptoms. Coexisting medical problems were common and further obscured the correct diagnosis. Survival was significantly shorter in those patients with symptoms of less than 6 months' duration. Primary pulmonary hypertension should be considered in the differential diagnosis in elderly patients with unexplained dyspnea and chest pain.
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PMID:Primary pulmonary hypertension in the elderly. 174 99

H65-RTA is an immunoconjugate that consists of the A chain of ricin (RTA), a ribosomal-inhibiting protein, coupled to a murine monoclonal antibody (H65) directed against the pan-T-cell antigen CD5. The CD5 antigen is heterogeneously expressed on cutaneous T-cell lymphoma tumor cells, but is not expressed on normal cells except lymphocytes. A phase I trial was therefore conducted in which 14 patients with cutaneous T-cell lymphoma progressive on other therapies were treated with up to three cycles of H65-RTA. The maximal tolerated dose (MTD) of H65-RTA was 0.33 mg/kg/d administered intravenously for 10 days as defined by dyspnea at rest at higher doses. Other reversible side effects included myalgia, mild hypoalbuminemia with weight gain, pedal edema, fatigue, fevers, and chills. Six patients received more than one cycle of H65-RTA without increased side effects compared with the first cycle. Pharmacokinetic analysis showed that peak serum drug levels were dose-dependent, and ranged from 1.13 to 5.56 micrograms/mL, with a terminal half-life ranging from 1.0 to 2.9 hours. The development of antibodies against the immunoconjugate was associated with a lower peak drug level, but not with enhanced side effects. Partial responses lasting from 3 to 8 months were documented in four patients. Three of the responding patients received more than one cycle of H65-RTA in the presence of anti-immunoconjugate antibodies. The results from this phase I trial suggest that H65-RTA is an active drug in the treatment of cutaneous T-cell lymphoma. The immunoconjugate may be safely administered repeatedly, even in the presence of anti-immunoconjugate antibodies, with responses noted. Additional studies at the MTD are needed to define the response rate in this disease.
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PMID:Phase I trial of H65-RTA immunoconjugate in patients with cutaneous T-cell lymphoma. 187 84

Endralazine, a novel vasodilator related to hydralazine, exhibits a longer half-life and is only minimally influenced by acetylator status. The antihypertensive action of once daily endralazine has been studied in 17 patients previously controlled with an antihypertensive regimen which included hydralazine and a beta-blocker. Hydralazine was discontinued but other medications were unchanged. Pre-study dosage of hydralazine ranged from 25 mg b.i.d. to 50 mg g.i.d., mean daily dose 126.5 mg. Endralazine was started at a dose of 10 mg o.d. and increased by 10 mg to a maximum of 40 mg o.d. until seated DBP was controlled below 95 mmHg. All 17 patients completed the study. Seated BP significantly decreased from 147.5/99.7 to 133.8/83.9 and standing BP from 145.8/99.2 to 133.6/87.3 mmHg. Ten patients (59%) were successfully controlled with endralazine once daily but 7 patients required twice daily dosage schedules because of lack of BP control at 24 h after dosing or excessive hypotension shortly after dosing. Other adverse effects were headache, palpitations and fatigue. There was a statistically insignificant average weight gain of 1 kg but pedal edema was not observed. Endralazine is an effective antihypertensive agent with adverse symptoms similar to those experienced with hydralazine.
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PMID:Evaluation of once daily endralazine in hypertension. 375 43

A hypertensive urgency should be distinguished from a hypertensive emergency. Although the distinction may not always be obvious, certain guidelines may help the clinician determine which therapeutic approaches are most appropriate for each patient. Hypertensive emergencies include those conditions in which new or progressive severe end-organ damage is present and a delay in appropriate therapy might result in permanent damage, progression of complications, and a poor prognosis. Hypertensive urgencies include those conditions with minimal to no obvious end-organ damage in which blood pressure should be lowered expeditiously. The risk of immediate complications or organ damage is less likely to occur, and thus the immediate prognosis is better, although the ultimate prognosis, if untreated, is poor. There is a marked individual, racial, sexual, and age difference in the ability to tolerate high intraarterial pressure, as evidenced by patients' symptoms and signs of end-organ damage. Patients may have no symptoms of elevated blood pressure until significant intraarterial levels are reached. If symptoms are present, they may include headache, dizziness, blurred vision, shortness of breath (especially with exertion), chest pain, rapid pulse, palpitations, malaise and fatigue, nocturia, or pedal edema. Signs of hypertensive disease vary and depend not only on the level of blood pressure but also include funduscopic changes with arteriolar narrowing, atrioventricular nicking, hemorrhages, exudates or papilledema, central nervous system changes and neurologic abnormalities, cardiac changes with gallop rhythm, cardiomegaly, tachycardia, ectopic ventricular beats, left ventricular hypertrophy or signs of congestive heart failure, pulmonary edema, and signs of renal insufficiency.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hypertensive emergencies and urgencies: pathophysiology and clinical aspects. 394 53

The Southwest Oncology Group (SWOG) studied the response rate and toxicity of merbarone (1,000 mg/m2 IV continuous infusion days 1-5, q 21 days) in patients with advanced metastatic renal cell carcinoma. Among 36 eligible patients, there was one partial response for a response rate of 3% (95% C.I. 0.1-15%). There were no mixed responses. There were no treatment related deaths or adverse drug reactions. Significant anemia, diarrhea, and hypercalcemia were observed. Mild to moderate degrees of malaise/fatigue/lethargy, dizziness/vertigo, hyperglycemia, creatinine increase, nausea, vomiting, weight loss, pedal edema, dyspnea, and granulocytopenia were noted. Merbarone does not have significant activity as a single agent in advanced renal cell carcinoma.
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PMID:Phase II evaluation of merbarone in renal cell carcinoma. 786 Feb 33

Constrictive pericarditis is a pathologic condition that may lead to significant morbidity. Definitive management of constrictive pericarditis requires pericardiectomy. A retrospective review of pericardiectomy for constrictive pericarditis at the Ochsner Clinic was undertaken. Twenty-one patients (17 male, four female) underwent pericardiectomy for constrictive pericarditis between January 1969 and June 1994. Ages ranged from 15 to 66 years (mean 41.5 years). Pedal edema, dyspnea, fatigue, and chest pain were the most common symptoms. Fifteen patients had important comorbidities. Preoperative New York Heart Association (NYHA) class was I (2), II (8), III (6), IV (5). Mean preoperative catheterization data, available in 17 patients (81%), demonstrated elevated intracardiac pressures (right atrial 17.4 mm Hg, right ventricular end-diastolic 22.4 mm Hg, pulmonary artery 26.2 mm Hg, pulmonary capillary wedge 20.2 mm Hg, left ventricular end-diastolic 20.1 mm Hg). A total pericardiectomy was performed in nine patients (sternotomy 8, thoracotomy 1). Pericardiectomy limited anteriorly to the phrenic nerves was performed in 11 patients (sternotomy 9, thoracotomy 2). One partial pericardiectomy was performed through a sternotomy. Cardiopulmonary bypass was used in six patients (29%). Mean hospital stay was 12 days (preoperative 4.2, postoperative 7.67). All patients achieved NYHA Class I postoperatively. Sixteen patients were discharged in sinus rhythm. No early mortality (<30 days), or major postoperative complications were observed. Pericardiectomy for pericardial constriction can be performed safely low morbidity and mortality and can favorably impact the natural history of this debilitating condition.
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PMID:Pericardiectomy for pericardial constriction. 860 Aug 53

The safety and tolerability of mibefradil, a selective T-type calcium channel antagonist, were evaluated in 3,430 patients with essential hypertension and chronic stable angina pectoris treated in 15 double-blind placebo and active-controlled clinical trials and 2 open-label, long-term safety studies. Of these patients, 2,636 were treated with the recommended doses of mibefradil (50 and 100 mg) and form the basis of this report. With the 50-mg dose of mibefradil, the incidence of each adverse event was similar to, or lower than, that observed in the placebo-treated patients. Treatment with the 100-mg dose was associated with a slightly higher incidence compared to placebo of dizziness (2.1% vs 1.8%), leg edema (3.5% vs 1.4%), fatigue (2.1% vs 1.4%), and lightheadedness (2.1% vs 0.4%). The incidence of headache (4.6%) and angina pectoris (1.1%) was more frequent in patients treated with placebo. In active-controlled trials, a lower incidence of pedal edema (5.1%) was observed with mibefradil compared to amlodipine (25.7%), diltiazem SR/CD (9.4%), or nifedipine SR/GITS (17.4%). Overall, mibefradil was better tolerated than amlodipine and nifedipine SR/GITS and was as well tolerated as diltiazem SR/CD. Rates of premature discontinuation due to clinically adverse experiences with the 50- and 100-mg doses were 2.5% and 3.5%, respectively, compared with placebo (3.5%). No consistent pattern of laboratory adverse experiences were observed for mibefradil. Sinus bradycardia (heart rate <45 beats/minute) and first-degree atrioventricular block were the only relevant treatment-emergent electrocardiographic changes that occurred more frequently with mibefradil than with placebo. No evidence of first-dose effects was observed in mibefradil-treated patients, and withdrawal effects were not observed in clinical trials. There were no clinically important differences in safety profiles in the demographic subgroups for age, gender, or race. The results of this comprehensive safety analysis indicate that treatment with the recommended doses of mibefradil is well tolerated and safe.
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PMID:Safety of mibefradil, a new once-a-day, selective T-type calcium channel antagonist. 928 53

The safety and efficacy of Amlodipine (AML) for mild to moderate hypertension was evaluated in a "real life" setting. This open non-comparative trial included 123 men and 143 women (age 30-91 years, mean 59.4). All had sitting diastolic blood pressure (DBP) between 95 and 115 mmHg, confirmed in most by 2 baseline measurements, 2 weeks apart. Eligible patients were given AML 5 mg daily as add-on or monotherapy and were evaluated 4 weeks later. If DBP was then > 90 mmHg, the daily dose was raised to 10 mg; those with < 90 mmHg remained on 5 mg. AML was continued for 8 weeks. Other BP-lowering drugs were unchanged. Of the original 266 patients 22 (8.2%) withdrew due to adverse events (AE), and others were protocol violators, lost to follow-up or withdrew, leaving 211 available for efficacy analysis. In this major group BP was reduced from 165 +/- 15/101 +/- 4 to 139 +/- 11/83 +/- 5 after 12 weeks of AML (p < 0.05). The reduction was greater in those under 70 years, from 173 +/- 12/100 +/- 5 to 142 +/- 12/80 +/- 4 (p < 0.05). In those with BMI > 30 kg/m2, BP decreased from 165 +/- 15/101 +/- 5 to 140 +/- 12/83 +/- 5 (p < 0.05). Mean change in heart rate was -1.5 bpm (p < 0.05). Mean final AML dose was 5.5 mg/day. The most common AML-related AE requiring cessation of the drug was pedal edema in 2.6% of the 266 patients; in 3.7% it persisted during therapy. Other AE occurring in > 1% were dizziness in 1.8%, headache 1.5%, flushing 1.1% and fatigue 1.1%. We conclude that AML is an effective and well-tolerated antihypertensive suitable for most hypertensive patients.
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PMID:[Multicenter community-based trial of amlodipine in hypertension in Israel]. 1095 90

Hypocalcemia is a relatively uncommon reversible cause of congestive heart failure. There are a few reports of hypocalcemic children who developed congestive heart failure associated with hypoparathyroidism. In all these patients, however, cardiac failure did not occur before the age of nine years. In addition, other striking noncardial manifestations of hypoparathyroidism, e.g., convulsive seizures, had been present prior to cardiac symptoms. We report on a 3.7 year old girl with mitral insufficiency and severe cardiac failure due to hypocalcemia secondary to familial hypoparathyroidism. The infant's mother was suffering from idiopathic hypoparathyroidism, but her own history lacked any evidence for parathyroid hormone deficiency. On admission, she presented with fatigue, dyspnea, and pedal edema. Liver edge was palpable 4 cm below the right costal margin, and a 3/6 systolic murmur was heard. A chest x-ray showed cardiac enlargement; electrocardiogram demonstrated a prolonged QTc interval of 0.46 s. The echocardiography revealed a cleft in the mitral valve with mitral insufficiency and markedly reduced contractility of the left ventricle. Laboratory studies demonstrated a low total serum calcium level of 1.3 mmol/l; serum magnesium level was slightly decreased (0.5 mmol/l), and parathyroid hormone level was not detectable. Partial monosomy of chromosome 22 was excluded. Ophthalmological examination, audiometry, and renal ultrasonogram were normal. Oral calcium supplementation and anticongestive therapy with metildigoxin, furosemid, and captopril was initiated but no improvement of the heart failure occurred. However, normalization of serum calcium level by calcium infusions caused prompt clearing of the clinical symptoms, complete normalization of liver size, reduction of cardiac enlargement (thoracic ratio decreased from 0.68 to 0.57), and marked improvement in contractility (left ventricular shortening fraction increased from 21% to 34%). The QTc interval decreased to 0.39 s. The successful treatment following normalization of serum calcium level proved the superiority of hypocalcemia over mitral valve insufficiency in the etiology of the cardiac failure. To our knowledge, this is the first report of congestive heart failure due to hypocalcemia as the first manifestation of hypoparathyroidism in childhood. Hypocalcemia should be kept in mind in any congestive heart failure in children with or without underlying cardiac malformation.
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PMID:[Hypocalcemia-induced heart failure as the initial symptom of hypoparathyroidism]. 1102 Dec 71

With the availability of better treatment and prophylactic regimens for the infectious complications of human immunodeficiency virus (HIV), the non-infectious complications are gaining greater attention. HIV-related pulmonary arterial hypertension (HIV-PAH) is one of these. The incidence of HIV-PAH is estimated at 0.5% of HIV-infected individuals. The pathogenesis remains unclear. Patients present with symptoms as diverse as progressive shortness of breath, pedal edema, dry cough, fatigue, syncope, as well as chest pain. Chest X-ray always shows cardiomegaly and prominent pulmonary artery, and evidence of right ventricular hypertrophy can be seen from the electrocardiogram. The pulmonary arterial systolic pressure, diastolic pressure and pulmonary vascular resistance from right heart catheterization are increased. There are a few small studies showing the benefit of prostacyclin analog (epoprostenol and iloprost) and bosentan. The role of antiretrovirals remains controversial, as do those of other agents such as calcium channel blockers and anticoagulants. The prognosis of HIV-PAH is grave. Two thirds of HIV-PAH related mortality is usually secondary to consequences of pulmonary hypertension, with the worst survival noted in New York Heart Association (NYHA) functional class III-IV. The probability of survival in one series was 73%, 60% and 47% at one, two and three years, respectively.
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PMID:HIV-related pulmonary hypertension. 1719 95


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