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)

Recently there has been extensive development of orally active angiotensin converting enzyme (ACE) inhibitors in addition to those already marketed, for example, captopril, enalapril, lisinopril and ramipril. It was initially thought that ACE inhibitors were likely to be most useful as antihypertensive agents in conditions in which circulating renin and angiotensin II were elevated. However, it is now clear that they can also lower arterial pressure when plasma renin is not high. In addition, they have beneficial effects in cardiac failure. Thus, captopril, enalapril, lisinopril and ramipril can be used in the treatment of mild to moderate hypertension either alone or in conjunction with diuretics or calcium antagonists. Broadly speaking, efficacy appears to be similar to that of beta-blockers or diuretics. Unfortunately, however, there are no long term studies comparing one ACE inhibitor with another or with other classes of antihypertensive agents. Furthermore, there are no prognostic studies which show that use of ACE inhibitors reduces morbidity or mortality in hypertension. Many new ACE inhibitors are undergoing clinical assessment, including alacepril, cilazapril, fosenopril, perindopril, quinapril and ramipril. The drugs vary, in that some exist in the active form whereas others are prodrugs which are converted to the active agent following absorption. In addition they each possess one of several ligands, for example, carboxyl, phosphinyl or sulfhydryl groups, and so vary in their affinity for ACE. Although many of these agents are renally excreted, a small number are metabolised via the liver (e.g. quinapril and spirapril) and this may prove advantageous in the presence of renal impairment. In common with captopril and enalapril, the new ACE inhibitors inhibit the renin-angiotensin system and initial results suggest that they are effective in lowering blood pressure in essential hypertension. Furthermore, they reduce systemic vascular resistance in the absence of a reflex tachycardia. There are a number of adverse effects which are attributable to the pharmacological mechanism of the ACE inhibitors as a group; these include hypotension, particularly in patients with high renin levels, prior diuretic use, renal impairment or in the elderly. Additional adverse effects may relate to chemical structure. The high incidence of adverse effects noted in early studies related to excess dosage and to the presence of a sulfhydryl group, which the more recently developed ACE inhibitors lack. The adverse effects most commonly reported with established and new ACE inhibitors include headache and fatigue, cough, skin rashes, hypotension and diarrhoea. As a group, ACE inhibitors have an acceptable but not negligible adverse effect burden.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Angiotensin converting enzyme inhibitors and moderate hypertension. 222 19

Caroli's disease is one of the rare congenital conditions associated with the cystic dilatation of intrahepatic bile ducts. This is a case report of a 41-year-old Japanese male who complained of jaundice and general fatigue at the age of 34 for the first time. He was clinically diagnosed as having Caroli's disease by physical examination and image analyses study. The patient died after seven years and three months from the onset of the disease on account of renal function impairment. An autopsy was performed, revealing cystic dilatation of the intrahepatic bile duct, associated with a cirrhotic liver and also evidence of portal hypertension, substantiated by esophageal varices and splenomegaly. The liver weighed approximately 2,200 g. A histological investigation revealed typical morphological evidence of cirrhotic glomerulopathy and tubular degeneration with the presence of calcium casts in the dilated tubuli. The lung revealed diffuse alveolar damage with partial organization associated with remarkable polymorphonuclear and macrophagic infiltration. In this paper, the pathogenesis of the cirrhotic change, biliary duct abnormality and potential malignant transformation in the liver are discussed in relation to Caroli's disease.
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PMID:Caroli's disease associated with liver cirrhosis. An autopsy case. 225 97

Numerous studies report controversial results about the occurrence and role of cardiodepressant substances in various forms of circulatory shock. We investigated the net inotropic effect of the low molecular weight fraction (mol wt less than or equal to 1,000) of plasma in prolonged canine hypovolemic traumatic shock using an in vitro guinea pig papillary muscle assay (isotonic mode). The shock plasma fractions (ultrafiltrates) after 4 hr of hypotension (mean arterial blood pressure 40-50 mm Hg) and immediately post-reinfusion significantly depressed papillary muscle function (P less than .02). The extent of papillary muscle shortening was decreased by 49.5 +/- 9.9% in pre- and 50.6 +/- 10.0% in post-reinfusion plasma ultrafiltrates (mean values +/- standard error of the mean; n = 6 shock experiments). In contrast, both the plasma ultrafiltrates from ten non-anesthetized healthy dogs and the control ultrafiltrates obtained prior to onset of shock in the experiments (-6.4 +/- 2.6; n = 6) induced no significant change of the in vitro performance of papillary muscle contraction. These results were achieved with plasma fractions in which ionized calcium and pH were adjusted to concentrations equivalent to the bioassay solution. Lactate acidosis and severe hypoglycemia (1.97 +/- 0.43 mM post-reinfusion) occurred in the shock experiments. Lack of energy substrate (glucose) was not responsible for the in vitro depression. Four depressive shock ultrafiltrates with glucose concentrations adjusted to control ultrafiltrate levels induced a 66.6 +/- 8.8% decrease in the extent of papillary muscle shortening. These results suggest that the possible occurrence of high net negative inotropic activity in plasma, especially just post-reinfusion, may play a role in the pathogenesis of irreversible circulatory shock.
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PMID:Net inotropic plasma activity in canine hypovolemic traumatic shock: low molecular weight plasma fraction after prolonged hypotension depresses cardiac muscle performance in vitro. 231 Dec 3

The purpose of these experiments was to examine the influence of various fluid replacement drinks on exercise-induced disturbances in homeostasis during heavy exercise. Nine trained cyclists performed constant load exercise on a cycle ergometer to fatigue on three occasions with 1-week separating experiments. The work rate was set initially at approximately 85% of VO2max (range 82-88%) with fatigue being defined as a 10% decline in power output below the initial value. During each experiment subjects consumed one of the following three beverages prior to and every 15 min during exercise: (1) non-electrolyte placebo (NEP; 31 mosmol.kg-1); (2) glucose polymer drink containing electrolytes (GP; 7% CHO, 231 mosmol.kg-1), and (3) electrolyte placebo drink without carbohydrate (EP; 48 mosmol.kg-1). Both the GP and EP beverage contained sodium citrate/citric acid (C) as a flavoring agent while C was not contained in the NEP drink. Although seven of nine subjects worked longer during the GP and EP treatment when compared with the NEP trial, the difference was not significant (P greater than 0.05). No differences (P greater than 0.05) existed between the GP and EP treatments in performance time. Exercise changes in rectal temperature, heart rate, delta % plasma volume and plasma concentrations of total protein, free fatty acids, glucose, lactate, potassium, chloride, calcium, and sodium did not differ (P greater than 0.05) between trials.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fluid replacement drinks during high intensity exercise: effects on minimizing exercise-induced disturbances in homeostasis. 231 95

We present the case of a woman with classical osteitis fibrosa cystica generalisata von Recklinghausen, caused by a single adenoma of the left inferior parathyroid gland. After six months with increasing bone pain, pathological fractures and cystic lesions radiologically, hyperparathyroidism was diagnosed by persistent elevated levels of serum calcium, and elevated levels of PTH. Surgical extirpation of the parathyroid adenoma caused a period with severe hypocalcemia followed by complete clinical restitution. The diagnosis should be considered in any case of persistent bone pain and uncharacteristic fatigue.
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PMID:[Osteitis fibrosa cystica von Recklinghausen]. 232 Dec 26

We have measured the distribution of intracellular calcium concentration in isolated single muscle fibres from Xenopus laevis using the fluorescent calcium indicator fura-2 with digital imaging fluorescence microscopy. Under control conditions, resting and tetanic calcium were uniform throughout a fibre. When fatigue was produced using a prolonged, high-frequency tetanus, the distribution of calcium within muscle fibres became non-uniform, with greater levels near the outer parts of a fibre than near the centre. This non-uniform distribution of calcium was rapidly abolished by lowering the stimulation frequency. When fatigue was produced using a series of repeated intermittent tetani, tetanic calcium showed an initial small increase, followed by a decrease as stimulation was continued. The distribution of calcium remained uniform under these conditions. Calcium distribution was also uniform during recovery from intermittent tetanic stimulation. Although fibres varied considerably in their fatigue resistance, the time for tension to fall to 50% was correlated with the reduction in tetanic calcium seen at this time. These results indicate that there are at least two patterns of reduced calcium release that can contribute to the development of fatigue. The appearance of a calcium gradient is consistent with impaired t-tubular conduction, while a uniform reduction of calcium is likely to be due to the action of metabolic factors on systems controlling calcium homeostasis within the cell.
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PMID:Spatial gradients of intracellular calcium in skeletal muscle during fatigue. 233 50

A 64-year-old female patient was admitted to our department for fatigue, pain in the right upper abdomen, obstipation, and meteorism. The laboratory findings showed total calcium and ionized calcium elevated, phosphate close to lower limit, and parathyroid hormone increased. T1-201/Tc-99m subtraction scintiscan of the neck and upper mediastinal region did not give any evidence of isolated enhanced uptake suggesting the presence of parathyroid adenoma. After further increases in calcium and parathyroid hormone level T1-201 whole-body scan and single photon emission computed tomography of the thoracic region were performed. These revealed a circumscribed T1-201 uptake in the mediastinum immediately cranial ventral to the heart base. The postcontrast transmission computed tomography of this area confirmed the finding of the T1-201 scintigraphy with a 4 x 3 x 2 cm tumor. After sternotomy and surgical removal of the mediastinal parathyroid adenoma (chief cell adenoma), calcium and parathyroid hormone levels returned to normal values.
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PMID:Localization of mediastinal parathyroid adenoma by T1-201 scintiscan and SPECT. 235 26

Sick sinus syndrome (SSS) is usually a disease of the elderly produced by idiopathic degeneration of the sinoatrial node. Its initial manifestations range from asymptomatic to nonspecific and include palpitations, fatigue, confusion, and even syncope and sudden death. Electrocardiographic evidence of SSS includes inappropriate sinus bradycardia, sinus pause or arrest, or sinus exit block. These bradyarrhythmias may alternate with tachyarrhythmias, especially atrial fibrillation, to create the tachycardia-bradycardia syndrome. The diagnosis of SSS may be established by electrocardiography or ambulatory monitoring in the majority of cases. Medications such as digoxin, beta-blockers, and calcium blockers may initiate or worsen the manifestations of SSS. Permanent pacing is indicated for symptomatic bradyarrhythmias. Progression of SSS is mostly dependent on the presence and severity of associated coronary or hypertensive heart disease.
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PMID:Update on sick sinus syndrome, a cardiac disorder of aging. 240 55

The calcium-entry blocker flunarizine (Sibelium; Janssen) was compared with the beta-adrenoreceptor-blocking agent propranolol in the prophylaxis of migraine. Fifty-eight patients were entered into a double-blind 4-month treatment trial. Patients in whom beta-blockers were contraindicated were excluded from the trial. At the end of the trial 28 patients had received 10 mg flunarizine at night during the study, 29 patients had received 60 mg propranolol 3 times a day and 1 patient was withdrawn. Both groups responded well; and there was a 4-fold drop in frequency of attacks. There was no significant difference between the two groups in terms of patient profile, onset of response to therapy, final response to therapy, incidence of dropout from the trial or incidence of side-effects. Side-effects for flunarizine were weight gain (9 patients) and tiredness (6), and for propranolol sleep disturbances including nightmares (6), tiredness (8), mental changes (e.g. irritability) (3) and weight gain (4). Both flunarizine and propranolol are useful drugs for migraine prophylaxis and can be used effectively as first-line drugs. The low incidence of generally mild side-effects with flunarizine may make it preferable to many of the agents at present in use for migraine prophylaxis.
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PMID:A comparative trial of flunarizine and propranolol in the prevention of migraine. 240 46

Theophylline improves diaphragmatic contractility of the respiratory muscles both in isolated muscle preparations, as well as in animals and normal human beings. Furthermore, theophylline restores diaphragmatic fatigue and prevents fatigue of the diaphragm when given prophylactically. Finally, it was recently shown that theophylline improves diaphragmatic function in COPD patients, all of whom were CO2 retainers (PaCO2 53 +/- 3 mm Hg) and hypoxemic (PaO2 57 +/- 8 mm Hg). Patients improved transdiaphragmatic pressure and were less susceptible to fatigue. Presently the mechanisms of action of theophylline regarding its effects on diaphragmatic function are not fully elucidated. Experimental evidence, however, suggests that theophylline may have an effect on transmembrane calcium movements by blocking adenosine receptors.
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PMID:Effect of theophylline on respiratory muscle function. 241 Feb 4


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