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

This study describes six generations of a family with autosomal dominant cardiac conduction system and myocardial disease with recognizable clinical stages. A 20 year follow-up of nine family members, a medical questionnaire of 196, electrocardiographic screening of 91, noninvasive testing of 20, and catheterization with endomyocardial biopsy of six are the basis of this report. The clinical stages are as follows: Stage I occurs in the second and third decades of life and is characterized by an absence of symptoms, normal heart size, sinus bradycardia, and premature atrial contractions. Stage II is marked by first-degree atrioventricular block in the third and fourth decades. Stage III occurs in the fourth and fifth decades and is accompanied by chest pain, fatigue, lightheadedness, and advanced atrioventricular block followed by the development of atrial fibrillation or flutter. Stage IV, in the fifth and sixth decades of life, is characterized by congestive heart failure and recurrent ventricular arrhythmias. Light microscopy of right ventricular endomyocardial biopsy specimens from patients in stage II revealed very mild fibrosis; electron microscopy of the specimens demonstrated mild dilatation of tubules, mitochondrial swelling, and minimal myofibrillar loss. Biopsy specimens from patients with stage III disease were similar to those from patients with stage II disease except for an increase of myofibrillar loss. The stage IV specimens had diffuse fibrosis and more severe tubular dilatation, mitochondrial cristolysis, and myofibrillar loss. At autopsy in the proband, the atrial changes were more severe than the ventricular and were especially marked in the sinoatrial and atrial myocardium. Early recognition of the disease and use of pacemakers and antiarrhythmic agents have proved beneficial for affected family members. Thorough family studies of patients with conduction system disease and/or dilated cardiomyopathy are necessary to better understand the hereditary basis and natural course of this category of disease.
 ...
PMID:Evolution of a hereditary cardiac conduction and muscle disorder: a study involving a family with six generations affected. 370 75

Mitral valve prolapse (MVP) now is a commonly recognized syndrome with an apparent prevalence of approximately 4-6%. It appears to occur more frequently in females and occasionally it is familial. In most instances, the syndrome is idiopathic, although it occurs in association with many other conditions, particularly Marfan's syndrome, rheumatic heart disease, coronary heart disease, congestive cardiomyopathy, ostium secundum atrial septal defect, Ehlers-Danlos syndrome or abnormalities of the thoracic cage. The majority of patients with the syndrome have minimal, if any, symptoms and have a benign course. When symptoms do occur, more frequently they are palpitations, chest pain, dyspnea on exertion or fatigue. Neuropsychiatric symptoms or even transient ischemic episodes may occur rarely. Very rarely, complications such as severe mitral regurgitation, arrhythmias or infective endocarditis may occur. Characteristically, patients have a midsystolic click, occasionally followed by a systolic murmur. The timing of the click and the onset of the murmur usually is variable, depending on the ventricular volume. The electrocardiogram frequently shows ST-T wave changes. The diagnosis usually can be confirmed by echocardiography or left ventricular angiography. Most patients with MVP require no treatment other than reassurance. If a systolic murmur is present, prophylaxis against infective endocarditis during dental work probably is useful. Patients with palpitations or chest pain usually respond well to treatment with propranolol. Patients with progressive severe mitral regurgitation require mitral valve replacement.
 ...
PMID:Mitral valve prolapse. 699 66

The efficacy and safety of cilazapril in chronic heart failure have been extensively investigated in an international clinical program in patients with underlying chronic heart failure with ischemic heart disease or dilated cardiomyopathy. Cilazapril in single doses of 1.25-5 mg produced a significant dose-dependent reduction in pulmonary capillary wedge pressure and systemic vascular resistance and a significant increase in cardiac index. In placebo-controlled studies, 1-5 mg of cilazapril once daily for 12 weeks prolonged predose exercise test duration and improved New York Heart Association classification status and signs and symptoms of chronic heart failure, including paroxysmal nocturnal dyspnea. Up to 86% of patients receiving these dosages had improvement, with only 12% of patients requiring the higher dose, 5 mg. These data indicate that cilazapril is effective when administered once daily to patients with chronic heart failure receiving concomitant therapy with digitalis and/or a diuretic. The safety of cilazapril in patients with chronic heart failure has been evaluated in 1,163 patients administered from 0.5 to 15 mg once daily for treatment periods ranging from 1 day to 57 months. Cilazapril was administered to 500 patients for at least 6 months, 264 patients for at least 1 year, and 101 patients for at least 2 years. The most frequently occurring adverse events were dizziness, coughing, dyspnea, fatigue, angina pectoris, and headache. Cilazapril was equally well tolerated by young and elderly patients. Treatment was discontinued due to adverse events in 12.9% of patients, mainly as a result of coughing (1.7%) and dizziness (1%). Forty-four patients (3.8%) died during cilazapril therapy or during a period without treatment. Of these deaths, 93% were due to cardiac causes, especially rhythm disturbances.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Heart failure therapy with cilazapril: an overview. 770 63

Interferon alpha is a biologic agent with demonstrated anti-tumor activity in a variety of hematologic and solid malignancies. Many patients treated with interferon experience acute toxicity manifested as a flu-like syndrome of fever, chills, myalgias, and malaise. However, fatigue, anorexia, bone marrow suppression, nausea, vomiting, dizziness, and confusion may also occur. Cardiotoxicity is a rare complication of interferon therapy that most frequently presents as transient episodes of hypotension and tachycardia, with few significant life-threatening cardiovascular effects reported. A small number of cases of suspected interferon-induced cardiomyopathy, all of which improved after discontinuing interferon, have recently been documented. We report a patient with multiple myeloma who developed severe congestive cardiomyopathy while receiving interferon alpha that did not reverse subsequent to discontinuation of interferon therapy. Although the patient had previously received doxorubicin, the presence on endomyocardial biopsy of a prominent intracellular lipid accumulation within myocytes and only grade 2 anthracycline cardiotoxicity suggested that other or additional factor(s) contributed to the severity of this patient's cardiomyopathy. Etiologies of cardiac dysfunction other than interferon and doxorubicin were excluded. While a direct cause-effect relationship between interferon alpha and irreversible congestive cardiomyopathy cannot be firmly established in this case report, patients who either concurrently or sequentially receive interferon and anthracyclines should be carefully monitored for evidence of cardiac toxicity.
 ...
PMID:Irreversible, severe congestive cardiomyopathy occurring in association with interferon alpha therapy. 771 76

It is well established that in patients with chronic heart failure, exercise capacity and clinical symptoms such as fatigue or dyspnea correlate poorly with the extent of left ventricular dysfunction. The increase in cardiac output caused by vasodilators, cannot be translated immediately into increased exercise capacity and peak oxygen consumption in patients with chronic heart failure. These observations have prompted the hypothesis that in chronic heart failure intrinsic abnormalities of skeletal muscle emerge that prevent acute improvement in peak VO2 and blood lactate accumulation. Studies using nuclear magnetic resonance demonstrate abnormal skeletal muscle metabolism during exercise, even in the absence of reduced flow or under ischaemic conditions. Histological examination of skeletal muscle reveals a variable extent of atrophy, increased interstitial cellularity and increase in type IIb fibres. Ultrastructural analysis shows abnormalities indicative of depressed oxidative capacity. Biochemical analysis of skeletal muscle biopsies demonstrates reduced activity of enzymes involved in aerobic metabolism and free fatty acid accumulation. These data indicate morphological, biochemical and metabolic alterations of skeletal muscle that should contribute significantly to the reduced muscle strength and rapid fatigue in patients with chronic heart failure. It has also been speculated that a generalized myopathy may occur in a subset of patients with dilated cardiomyopathy. These findings have clinical implications. Prolonged immobilization of patients with chronic heart failure was often suggested, is not practised anymore. Physical training in chronic heart failure has been shown to improve skeletal muscle function, exercise capacity and clinical symptoms in small controlled trials. Pharmacological treatment might be targeted for skeletal muscle disorders in patients with heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Congestive heart failure: from cardiac muscle to skeletal muscle]. 802 46

Dilated cardiomyopathy, perhaps chronic postviral fatigue syndrome as well as juvenile diabetes could be triggered by enteroviral infections. The frequency of sudden death after myocarditis and its relationship to enteroviral infections is disputed. Neonatal enteroviral disease is rare, but can be severe. It is also possible that enteroviruses pose a threat to immunocompromised patients, like bone marrow transplant recipients. Consequently, the emergence of chronic enteroviral diseases as a concept, prompted our attempts to produce an enteroviral vaccine. 1. Live attenuated enterovirus strains were previously in some cases shown to be suitable as vaccine candidates. We obtained neutralizing antibody titres ranging from 40-2560 against Coxsackie B3 virus (RD strain). Animals were protected to 90% against challenge infection. 2. Inactivated whole vaccine. We used beta-propiolactone to inactive Coxsackie B3 virus. 74% of the animals survived if the vaccine was prepared with Quil A matrix as adjuvant. The neutralisation antibody titres varied from < 5 to 320. By comparison aluminium hydroxide (p = 0.06) and Freund's adjuvant were inferior (p < 0.01). 3. Subunit vaccines. We have previously used the ISCOM (immunostimulatory complex) technology to produce a Coxsackie B3 subunit vaccine. High levels of neutralizing antibodies were obtained (512)-comparable to natural infection. All animals survived challenge infection after two booster doses with 16 nanogram of the ISCOM preparation. Limiting for this technique was the availability to include sufficient amount of antigenic protein material. In addition to neutralizing antibodies a cellular response might be obtainable. In conclusion we have shown that vaccine can be made against Coxsackie B3 virus with good protective effect and significant neutralisation antibody titre.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:High yield production of an inactivated coxsackie B3 adjuvant vaccine with protective effect against experimental myocarditis. 839 Jul 13

Molecular hybridization using an enterovirus group specific probe detected virus RNA in muscle biopsy samples from 25 of 96 cases of inflammatory muscle disease and similarly from 41 of 158 cases of postviral fatigue syndrome (PFS). Enterovirus RNA was detected in only two of 152 samples of control muscle. The inflammatory myopathy group comprised patients with polymyositis (PM), juvenile dermatomyositis (JDM) or adult dermatomyositis (DM), and all showed the presence of an inflammatory infiltrate and fiber necrosis on histological examination of a muscle biopsy sample. In contrast, muscle samples from the PFS group were histologically normal except for non-specific changes such as occasional single fiber atrophy. By analogy with enteroviral myocarditis, which can progress to a post-inflammatory disease with persistence of virus in myocardium and disposes to the rapid development of dilated cardiomyopathy, we propose that PFS syndrome may be a sequela of a previous inflammatory viral myopathy.
 ...
PMID:Persistence of enterovirus RNA in muscle biopsy samples suggests that some cases of chronic fatigue syndrome result from a previous, inflammatory viral myopathy. 840 78

Triciribine is a purine analogue which inhibits DNA and protein synthesis. We performed two studies to define its activity against metastatic breast cancer. The first study was a phase II study in 14 patients with metastatic breast cancer who had received two or fewer chemotherapy treatments. The treatment schedule was tricirbine 20 mg/m2 per day by 24-h infusion (CI) daily for 5 days every 6 weeks as recommended by a previous open phase I trial. When neither response nor toxicity was seen in the phase II trial, we assumed the starting dose was too low for this group of patients with good performance status and repeated the phase I trial in patients with metastatic breast cancer with good performance status. The starting dose was 35 mg/m2 per day using the same 5-day CI schedule, and starting doses were increased in subsequent cohorts of three patients in increments of 5 mg/m2 until toxicity occurred. In the initial (phase II) study, one patient had stable disease for 18 weeks (three courses), the remainder progressed. There were no significant toxic effects. In the subsequent phase I study, ten patients were treated until the study was closed. The maximum dose was 40 mg/m2. Two patients died, one each at the 35 and 40 mg/m2 levels, respectively, 3 months and 6 weeks after their last course, one without intervening disease progression. Both had severe hypertriglyceridemia (18- and 21-fold elevation) and severe fatigue. At postmortem examination, one had congestive cardiomyopathy, and the other had severe pancreatitis and hypothyroidism. One patient had severe exacerbation of psoriasis which made her bedridden for more than 30 days. Four patients had hyperglycemia. Plasma pharmacology studies showed erratic drug levels, presumably related to enterohepatic circulation. Postmortem pharmacology studies showed residual drug present as long as 12 weeks after the last dose. We conclude that triciribine is ineffective at all doses tested and at doses of > or = 35 mg/m2 has unacceptable toxic effects.
 ...
PMID:Phase I-II study: triciribine (tricyclic nucleoside phosphate) for metastatic breast cancer. 852 86

Cardiomyoplasty is a method for managing patients with dilated cardiomyopathy. We evaluated the means of carbon fiber electrode stimulation of the nerve to the latissimus dorsi muscle (LDM) in dogs to increase skeletal muscle contractility. Histochemical examination of biopsies of muscle electrically conditioned by a single pulse stimulator via the thoracodorsal nerve demonstrated transformation of muscle into fatigue resistant slow fibers without damage to muscle or nerve tissue. Canine experiments confirmed that carbon fibers are one of the best electrodes for chronic LDM stimulation. Between 1988 and 1992, we operated on ten patients, New York Heart Association (NYHA) Class III (4 patients) and Class IV (6 patients), with a mean left ventricular ejection fraction (LVEF) of 23%. The indications for cardiomyoplasty were idiopathic (7 patients) and ischemic (3 patients) cardiomyopathy refractory to maximum medical therapy. The operative procedure was performed via median sternotomy (5 patients) and left thoracotomy (5 patients). There was one operative mortality and two additional deaths during the late follow-up period. The mean postoperative LVEF increased to 27%. Functional class, quality-of-life, and ventricular performance were improved after cardiomyoplasty. Two of the surviving patients are in NYHA Class I, four in Class II, and one in Class III.
 ...
PMID:Electrostimulated cardiomyoplasty: from experimental to clinical studies. 917 Jan 44

The prognosis for patients with idiopathic dilated cardiomyopathy (DCM) is poor, although clinical features are variable. Prediction of outcome has been difficult in individual patients based on laboratory data. In some patients with DCM, myocardial damage secondary to viral or immune-mediated myocardial inflammation may persist. To objectively assess inflammation, we measured plasma concentrations of C-reactive protein (CRP) in 188 patients with idiopathic DCM over 5-8 years. All had dyspnea and fatigue at rest; all patients had a left ventricular ejection fraction less than 40% by echocardiography or by contrast or radionuclide ventriculography. We divided these patients into two groups: patients dying within 5 years following admission (n = 49) and the remainder surviving for at least 5 years (n = 139). CRP concentrations in the patients dying early were significantly higher than in the long-term survivors (1. 05 +/- 1.37 vs. 0.49 +/- 1.04 mg/dl, p < 0.05). Sixty-two percent of the patients with CRP>1.0 died within 5 years. In addition to other laboratory tests including electrocardiography and echocardiography, routine CRP measurements proved to be valuable for identifying high-risk patients who require special treatment strategies.
 ...
PMID:C-Reactive protein in dilated cardiomyopathy. 1054 75


<< Previous 1 2 3 4 5 6 Next >>