Gene/Protein Disease Symptom Drug Enzyme Compound
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 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both nature and prognosis of cardiac complications occurring in patients infected by the Human Immunodeficiency Virus-1 (HIV-1) have changed considerably since the introduction of highly acive and anti-retroviral triple therapy ("HART"). Opportunist cardiac infections have thus been displaced and side effects of drugs now occupy the primary aetiological role. Torsades de pointe may be exceptionally triggered by anti-infectious agents such as pentacarinat or trimethoprime-sulfamethoxazole, as are those induced by the association of ketoconazole and terfenadine or cisapride, the dangers of which are well known and the prevention more effective, especially with the association with HIV antiproteases which inhibit the cytochrome P450. The diagnosis of iatrogenic myocardial dysfunction is more difficult, except when it occurs acutely as with phosphonoformate (Foscarnet), or interleukine-2. Progressive cardiomyopathy caused by -interferon and dideoxynucleosides (zidovudine, didanosine and zalcitabine), reversible on withdrawal of the drug responsible in half the cases, should be distinguished from those due to the HIV itself (therapeutic relay) or to another associated cause (alcohol, coronary artery disease). The coronary complications of diseases treated by antiproteases usually occur in smokers whose cholesterol and triglyceride levels are rapidly increased with HAART. In a series of 9 patients (amongst 700 treated with the antiproteases), after the acute phase of myocardial infarction during which the interventional approach is often preferred, the medium-term prognosis is relatively good, on condition that the patients correct the hyperlipidaemia and give up smoking.
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PMID:[Cardiac side effects of anti-HIV agents]. 1097 35

Renal transplant recipients die of CVD at an accelerated rate compared with the general population. Successful management of CVD risk would prolong patient and renal allograft life, but management must begin early in the pretransplant period. By the time a renal transplant becomes available, patients often have advanced CVD because of prolonged and progressive renal disease. The most effective way to reduce premature CVD in renal transplant recipients is to address the problem of cardiac disease and vascular disease at the earliest stages in the natural history of progressive renal disease. Based largely on the success of such treatments in the general population, pretransplant modification may include the use of statins to control hyperlipidemia and ACE inhibitors to control elevated blood pressure. Elevated blood pressure has been related to the development of cardiomyopathy prior to transplantation; thus, therapeutic goals should be revised to include reversal of LVH. Longitudinal studies are needed to evaluate the effects of blood pressure lowering on LVH (and other echocardiographic abnormalities) in patients with progressive renal disease, patients on dialysis, and even following transplantation. Echocardiographic parameters have been shown to be stronger determinants of CVD mortality than conventional risk factors in the transplant population, and studies are needed to look at regression of these echocardiographic abnormalities with blood pressure control.
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PMID:Pretransplant management of end-stage renal disease patients to minimize posttransplant risk. 1115 31

We investigated the prevalence and characteristics of ischemic heart disease especially silent myocardial ischemia (SMI) and arrhythmia in need of careful observation in the exercise stress tests in the Total Health Promotion Plan (THP), which was conducted between 1994-96 for the purpose of measuring cardiopulmonary function. All workers (n = 4,918, 4,426 males) aged 18-60 yr old in an occupational field were studied. Exercise tests with an ergometer were performed by the LOPS protocol, in which the maximal workload was set up as a presumed 70-80% maximal oxygen intake, or STEP (original multistage protocol). ECG changes were evaluated with a CC5 lead. Two hundred and fifteen people refused the study because of a common cold, lumbago and so on. Of 4,703 subjects, 17 with abnormal rest ECG and 19 with probable anginal pain were excluded from the exercise tests. Of 4,667 who underwent the exercise test, 37 (0.79%) had ischemic ECG change, and 155 (3.32%) had striking arrhythmia. These 228 subjects then did a treadmill exercise test with Bruce protocol. Twenty-two (0.47% of 4,703) showed positive ECG change, 9 (0.19%) of 22 had abnormal findings on a 201Tl scan. 8 (0.17%) were diagnosed as SMI (Cohn I), in which the prevalence of hypertension, hyperlipidemia, diabetes mellitus, smoker and positive familial history of ischemic heart disease was greater than that of all subjects. In a 15-30 month follow up, none has developed cardiac accidents. Exercise-induced arrhythmia was detected in 11 (0.23%) subjects. Four were non-sustained ventricular tachycardia without any organic disease, 4 were ventricular arrhythmia based on cardiomyopathy detected by echocardiography, 2 were atrial fibrillation and another was WPW syndrome. It is therefore likely that the ergometer exercise test in THP was effective in preventing sudden death caused by ischemic heart disease or striking arrhythmia.
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PMID:[Silent myocardial ischemia and exercise-induced arrhythmia detected by the exercise test in the total health promotion plan (THP)]. 1132 53

The advent of potent antiretroviral drugs in recent years has had an impressive impact on mortality and disease progression in HIV-infected patients, so that issues related to long-term effects of drugs are of growing importance. Hyperlipidemia, hyperglycemia, and lipodystrophy are increasingly described adverse effects of highly active antiretroviral therapy (HAART), in particular when protease inhibitors are used. Hyperlipidemia is strikingly associated with the use of most available protease inhibitors, with an estimated prevalence of up to 50%. Because of the short observation period and the small number of cardiovascular events, epidemiological evidence for an increased risk of coronary heart disease in HIV-infected patients treated with HAART is not adequate at present; however, it is likely that shortly more data will accumulate to quantify this risk. Before starting HAART and during treatment it is reasonable to evaluate all patients for traditional coronary risk factors, including lipid profile. Among the drugs that are currently used in HIV+ patients, antibacterials, antifungals, psychotropic drugs and anti-histamines have been associated with QT prolongation or torsade de pointe, a life-threatening ventricular arrhythmia. Among the risk factors that may precipitate an asymptomatic electrocardiographic abnormality into a dangerous arrhythmia is the concomitant use of drugs that share the CYP3A metabolic pathway. Since most protease inhibitors are potent inhibitors of CYP3A, clinicians should be aware of this potentially dangerous effect of HAART. Anthracyclines are potent cytotoxic antibiotics that have been widely used for the treatment of HIV-related neoplasms. Their cardiotoxicity is well known, ranging from benign and reversible arrhythmias to progressive severe cardiomyopathy. The increased survival and quality of life of HIV+ patients emphasize the importance of a high awareness of adverse drug-related cardiac effects.
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PMID:Drugs and cardiotoxicity in HIV and AIDS. 1176 86

Cardiomyopathy and IHD are important morbid complications among renal transplant recipients. Age, diabetes, and sex remain important markers of risk. Smoking, hyperlipidemia, and hypertension appear to be the major reversible risk factors for IHD. Anemia and hypertension predict CHF. Definitive evidence on optimal intervention is lacking. Similarities in the renal transplant recipients to CRI patients with respect to cardiomyopathy and to the general population with respect to IHD suggest that extrapolation from those groups is reasonable in the interim.
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PMID:Factors governing cardiovascular risk in the patient with a failing renal transplant. 1188 35

Deficiency of amylo-1,6-glucosidase, 4-alpha-glucanotransferase enzyme (AGL or glycogen debrancher enzyme) is responsible for glycogen storage disease type III, a rare autosomal recessive disorder of glycogen metabolism. The AGL gene is located on chromosome 1p21, and contains 35 exons translated in a monomeric protein product. The disease has recognized clinical and biochemical heterogeneity, reflecting the genotype-phenotype heterogeneity among different subjects. The clinical manifestations of GSD III are represented by hepatomegaly, hypoglycemia, hyperlipidemia, short stature and, in a number of subjects, cardiomyopathy and myopathy. In this article, we discuss the genotypic-phenotypic heterogeneity of GSD III by the molecular characterization of mutations responsible for the disease on a collection of 18 independent alleles from the Mediterranean area. We identified by heteroduplex band shift, DNA direct sequencing, and restriction analysis, seven novel mutations (four nonsense point-mutations: R34X, S530X, R1218X, W1398X; two microinsertions: 1072insT and 4724insAA; and one bp deletion: 676DeltaG), together with two new cases carrying a IVS21 + 1 G --> A splicing site mutation previously described in Italian patients. Altogether, 15 alleles were characterized. The correlation between type of mutation and clinical severity was studied in six patients in whom both mutated alleles were detected. Our data confirm the extreme genetic heterogeneity of this disease, thus precluding a strategy of mutation finding based on screening of recurrent common mutations.
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PMID:Clinical and genetic variability of glycogen storage disease type IIIa: seven novel AGL gene mutations in the Mediterranean area. 1197 76

Cardiovascular disease (CVD) is the major cause of death among renal transplant recipients (RTRs), accounting for 17-50% of deaths. Both cardiomyopathy (congestive heart failure [CHF] and left ventricular hypertrophy [LVH]) and ischemic heart disease (IHD) are important complications of renal transplantation, although the morbid impact of cardiomyopathy has been overlooked until recently. Echocardiographic disorders and clinical CHF occur far more frequently in RTRs than in the general population, suggesting that renal transplantation may be a state of accelerated heart failure. In contrast, the incidence of IHD in RTRs is similar to that in the Framingham cohort. Age, diabetes, and gender remain important markers of risk for both disorders. Smoking, hyperlipidemia, and hypertension appear to be the major reversible risk factors for IHD, while anemia and hypertension are major reversible risk factors for cardiomyopathy. Definitive evidence on optimal intervention is lacking. Clinical trials are needed to define optimum targets for treatment of these risk factors, especially hypertension and anemia.
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PMID:Clinical epidemiology of cardiac disease in renal transplant recipients. 1264 73

Inherited metabolic disorders contribute importantly to adverse cardiovascular outcomes and affect all tissue types. This review summarizes some of the more important aspects. In the venous system, heterozygosities for the factor V Leiden and prothrombin 20210G > A mutations are common and occur in 4% and 1%, respectively, of caucasians. They confer a 2- to 3- fold increase in risk of venous, but not arterial, thrombosis. Marfan syndrome affects the systemic circulation and has a population prevalence of about 1 in 4000. The more than 200 mutations responsible are in the fibrillin-1 gene (15q21.1) and mediate the characteristic skeletal, lens and aortic changes. There are two potentially lethal inherited disorders of cardiac conduction, the long QT and Brugada syndromes. The prevalence for each is about 1 in 10,000. On the other hand, autosomal dominant hypertrophic cardiomyopathies are relatively common, at 1 in 500, but with variable penetrance. Mutations are in the sarcomere proteins and more than 140 are known. Hypertrophic cardiomyopathy may be confused with Fabry disease, for which effective treatment is now available. Mutations in several genes have been shown to produce dilated cardiomyopathy in the young, but there is as yet no specific treatment. In fatty acid oxidation disorders, arrhythmias and cardiomyopathy occur during acute decompensation. An important recently established cause of cardiomyopathy is carnitine transporter defect; it is treated effectively with oral carnitine. The autosomal dominant arrhythmogenic right ventricular dysplasia occurs with a prevalence of about 1 in 15,000 and presents with arrythmias and a dilated right ventricle. The mutations responsible have been mapped to chromosomes 1, 2, 10 and 14. Lysosomal storage disorders, the Ehlers-Danlos syndrome and other connective-tissue disorders affect cardiac valves and vessels. In addition to the relatively common inherited lipoprotein disorders familial hypercholesterolaemia and familial combined hyperlipidaemia, an important dominantly inherited lipid variable contributing to coronary risk is lipoprotein(a). The gene is localized to chromosome 6 and there is full expression in childhood. Elevated lipoprotein(a) levels contribute to the occurrence and severity of early-onset coronary disease and add to the already enhanced risk in patients with familial hypercholesterolaemia.
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PMID:Overview of inherited metabolic disorders causing cardiovascular disease. 1288 64

Mitochondriopathies (MCPs) are either due to sporadic or inherited mutations in nuclear or mitochondrial DNA located genes (primary MCPs), or due to exogenous factors (secondary MCPs). MCPs usually show a chronic, slowly progressive course and present with multiorgan involvement with varying onset between birth and late adulthood. Although several proteins with signalling, assembling, transport, enzymatic function can be impaired in MCP, most frequently the activity of the respiratory chain (RC) protein complexes is primarily or secondarily affected, leading to impaired oxygen utilization and reduced energy production. MCPs represent a diagnostic challenge because of their wide variation in presentation and course. Systems frequently affected in MCP are the peripheral nervous system (myopathy, polyneuropathy, lactacidosis), brain (leucencephalopathy, calcifications, stroke-like episodes, atrophy with dementia, epilepsy, upper motor neuron signs, ataxia, extrapyramidal manifestations, fatigue), endocrinium (short stature, hyperhidrosis, diabetes, hyperlipidaemia, hypogonadism, amenorrhoea, delayed puberty), heart (impulse generation or conduction defects, cardiomyopathy, left ventricular non-compaction heart failure), eyes (cataract, glaucoma, pigmentary retinopathy, optic atrophy), ears (deafness, tinnitus, peripheral vertigo), guts (dysphagia, vomiting, diarrhoea, hepatopathy, pseudo-obstruction, pancreatitis, pancreas insufficiency), kidney (renal failure, cysts) and bone marrow (sideroblastic anaemia). Apart from well-recognized syndromes, MCP should be considered in any patient with unexplained progressive multisystem disorder. Although there is actually no specific therapy and cure for MCP, many secondary problems require specific treatment. The rapidly increasing understanding of the pathophysiological background of MCPs may further facilitate the diagnostic approach and open perspectives to future, possibly causative therapies.
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PMID:Mitochondriopathies. 1500 63

The past 20 years have seen considerable advances in the field of organ transplantation that have together led to a notable increase in survival rates and a reduction in postoperative morbidity of transplant recipients. However, these advances have been accompanied by the appearance of other complications of transplantation, such as post-transplant hyperlipidaemia, hypertension and graft coronary vasculopathy (GCV). GCV is an accelerated form of atherosclerosis in transplanted hearts that has proven to be one of the most important late complications of heart transplantation and is the single most limiting factor for long-term survival. The most important factors favouring the development of hyperlipidaemia after heart transplantation are inappropriate diet in combination with reduced physical activity, adverse effects of immunosuppressive therapy (ciclosporin [cyclosporin], corticosteroids) and polygenic hypercholesterolaemia in combination with ischaemic cardiomyopathy. The treatment of hyperlipidaemia in heart transplant recipients results in a variety of complications and side effects. In particular, interactions between lipid-lowering drugs and immunosuppressive therapy have been observed. Early attempts at treatment with bile acid binding agents and nicotinic acid derivatives often proved insufficiently effective, and led to unacceptable adverse effects and significant disturbances of ciclosporin metabolism. Fibric acid derivatives provided moderate reductions in triglyceride and total cholesterol levels that were mostly--with the exception of gemfibrozil--accompanied by significant impairment of renal function. Probucol achieved only an unsatisfactory reduction in low-density lipoprotein (LDL) cholesterol. Omega-3 fatty acids lower cholesterol levels and improve endothelial function in heart transplant recipients; however, the significance of these effects is still under discussion. As in the general patient population, use of HMG-CoA reductase inhibitors (statins) achieved significant reductions in cholesterol levels. Use of these substances has resulted in significantly extended long-term survival times, significantly less GCV and fewer severe graft rejections. Selective cholesterol absorption inhibitors, administered with or without statins, could provide another treatment option for heart transplant patients with hypercholesterolaemia. In severe familial hypercholesterolaemia, which is rarely observed in heart transplant recipients, treatment with statins can be combined with extracorporeal cholesterol elimination procedures such as heparin induced extracorporeal LDL cholesterol precipitation (HELP). HELP enables total cholesterol levels to be kept within any desired target range, and has been used successfully and without adverse effects in heart transplant recipients.
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PMID:Management of hyperlipidaemia associated with heart transplantation. 1513 86


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