Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A total of 38 patients aged under 3 months with congenital heart disease (CHD) underwent palliative surgery between April, 1988 and March, 1993. The mean age at operation was 28.0 (range 1 to 87) days. Palliative procedures were: pulmonary artery banding (PAB) in 14 patients (IAA complex: 4, CoA complex: 6, AVSD: 2, TA: 2), Blalock-Taussig shunt (BTS) in 12 (TOF: 2, TGA: 1, AVSD: 1, PA-IVS: 3, PA-VSD: 3, PA-SV: 1, PA-AVSD: 1), Brock operation in 6 (PPS: 2, PA-IVS: 3, PA-SV: 1), Blalock-Hanlon operation (BH) with PAB in 2 (MA-SV: 2) and Norwood operation (NRD) in 4 (HLHS: 4). PAB of IAA or CoA complex was performed just after the repair of IAA or CoA. Overall operative mortality was 23% (PAB: 14.3, BTS: 8.3, Brock: 33.3, NRD: 100%). One week after PAB, pulmonary artery pressure (PAP) decreased significantly compared to the intraoperative PAP value after PAB (43.1 +/- 16.2, 32.3 +/- 9.0 mmHg, p < 0.05, respectively). Pulmonary artery index (PAI), which is an index of pulmonary artery growth, after BTS increased significantly compared to the preoperative value (mean follow-up interval: 22.1 months) (379.5 +/- 101.4, 159.3 +/- 51.2, p < 0.001, respectively). During Brock operation, balloon catheter was used in order to dilate pulmonary valve. One year after Brock operation, mean pressure gradient through the pulmonary valve 22.6 mmHg. Two-staged corrections of CHD will be performed both safely and successfully by effective palliations at the first stages in early infancy.
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PMID:[Palliative surgery of congenital heart disease in early infancy]. 751 26

The aggressive lipid-lowering goals recommended by the second Adult Treatment Panel (ATP II) have created an increasing demand for treatment with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. Fluvastatin is the first completely synthetic agent in this class and offers a considerable price advantage over the other HMG-CoA therapies. In May 1994, the Buffalo Veterans Affairs Medical Center Lipid Clinic adopted a fluvastatin-preferred program in which all patients who were recommended for an HMG-CoA reductase inhibitor would be treated with fluvastatin as a first-line agent. Fluvastatin was started at 20 mg daily and titrated to goal. Patients who were stable with other HMG-CoA reductase inhibitors were converted to fluvastatin as just described. Preliminary analysis shows that, for new patients, 20 mg of fluvastatin daily at bedtime reduced low density lipoprotein cholesterol (LDL-C) by an average of 22% (range, 5-32%). Preliminary results for patients converted from another HMG-CoA reductase inhibitor showed that fluvastatin produced an additional LDL-C reduction of 18% (range, 5-30%). With a daily dose of 20 mg fluvastatin, patients with no heart disease (primary prevention) achieved ATP II goals in 60% of cases. For patients with established heart disease (secondary prevention), the goals of ATP II are lower but, despite this, 30% of patients taking fluvastatin at 20 mg daily achieved these goals. The patients in both groups who failed to achieve ATP II goals were titrated to a 40 mg daily dose, but the results of this titration are not yet available. Pharmacoeconomic outcomes were favorable.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Outcome monitoring of fluvastatin in a Department of Veterans Affairs lipid clinic. 760 1

The aim of this manuscript is to review perturbations in bioenergetics that are redundant denominators in the diversity of factors mediating the pathogenesis and progression of coronary heart disease (CHD), congestive heart failure (CHF), hypertension and arrhythmias. This paper likewise assesses the pharmacodynamics of widely prescribed drugs that enhance cellular respiration, maintain positive inotropic, chronotropic, dromotropic cardiac effects, sustain myocardial biosynthesis, reverse the morbidity of heart disease, and assure low levels of toxicity commensurate with the agent's biocompatability. Conversely, it is essential to delineate the modality of xenobiotic drugs that inhibit energy transformations, enhance the pathogenesis of CHD, worsen survival in CHF, provoke arrhythmogenic effects, and induce serious side-effects. Documented evidence, derived from biochemical, physiological and pharmacological data sources, consistently links inhibited mitochondrial decarboxylation to aberrations in cholesterol metabolism, biosynthesis, and calcium balance. Underutilized citrates evolved from inhibited decarboxylation are degraded to acetyl CoA. The acetate is the source of steroid synthesis; its carbon atoms form the molecular basis for all endogenous cholesterol. Myocardial anoxia, a consequence of the atheromatous plaque, inhibits ATP production, impairs biosynthesis, induces negative cardiac inotropic and chronotropic effects, and enhances the pathogenesis of CHF. Inhibited decarboxylation is likewise a factor in the mobilization of in situ cardiac Ca2+, resulting in arrhythmias provoked by the cation's deficiency. The restoration of calcium homeostasis decreases peripheral vasotension, reducing hypertension. Parameters drawn from endocrinopathies and the new physiological dimension of microgravity are developed to illustrate the detrimental effect of inhibited bioenergetics on cardiac pathomorphism and cardiovascular dysfunction. In conclusion, anabolic agents, adjunctive to a productive life-style, can provide the rational basis for the prevention and treatment of cardiac diseases. Failure to understand mechanisms generating cardiovascular morbidity eventuates in ineffective and empirical treatment.
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PMID:Bioenergetics in the pathogenesis, progression and treatment of cardiovascular disorders. 858 65

The reproductive effects of metabolic disorders in women can be divided into four categories. The first of these is infertility. Galactosemia with its complication of ovarian failure is the disorder in this category. This complication may be prenatal in origin but whether this is so and its cause are unknown. The second category includes pregnancy effects of maternal metabolic disorders. The urea cycle disorder ornithine transcarbamylase (OTC) deficiency, maternal maple syrup urine disease and maternal homocystinuria are in this category. In the first two disorders, postpartum life-threatening illness due to metabolic crisis has occurred. Maternal homocystinuria is associated with a high risk for postpartum thromboembolic complications. The third category is the pregnancy effect of a fetal metabolic disorder. Pregnancies in which the fetus had long-chain hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) have been complicated by the life-threatening (HELLP) syndrome during the third trimester. Rapid recovery of the mothers followed delivery, on occasion by emergency cesarean section. The fourth category is the fetal effects (teratogenicity) from a maternal metabolic disorder. The best-known example of this is maternal phenylketonuria (PKU), which produces microcephaly, mental retardation, congenital heart disease and intrauterine growth retardation. Treatment with a low phenylalanine diet begun before conception or no later than the earliest weeks of the first trimester markedly reduces the risk to the fetus and can result in normal offspring. Other examples of teratogenicity may include maternal homocystinuria and maternal hypothyroidism.
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PMID:Reproductive effects of maternal metabolic disorders: implications for pediatrics and obstetrics. 882 3

The messenger RNA of the cardiac sarcoplasmic reticulum ATP-ase (SERCA-2a) increases in the left ventricle (LV) during ontogenic development but decreases in hypertrophy induced by increased afterload. Because of the frequency of increased left ventricular overload in congenital heart disease, the authors investigated to see if these increases were likely to interfere with the normal ontogenic program of expression of the SERCA-2a gene in the LV of sheep's foetus. A preductal coarctation of the aorta was realised by banding the transverse aorta (AoT) at 93 days' gestation in 9 foetus (CoA) matched with 9 healthy twin foetus (T). All the foetus underwent haemodynamic, anatomical, histological and molecular biological investigations 4 weeks later. The concentration of SERCA-2a mRNA in the LV was measured by hybridation of a Northern blot with a rat DNAc probe normalised with RNAr 18S. A coarctation was observed in all the CoA group and in none of the T. The ratio of LV weight/body weight was increased in 65% of CoA (p < 0.0001). The concentration of SERCA-2a mRNA in the LV was much reduced in CoA (average -28.6%) of the values observed in T (p = 0.003). Left ventricular hypertrophy of the sheep's foetus induced by pathological increases of afterload surpassed or slowed down the physiological ontogenic maturation of expression of the SERCA-2a gene in abnormalities of cardiac pump function.
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PMID:[A study of the expression of sarcoplasmic reticulum calcium ATP-ase gene in the left ventricle of the sheep's fetus submitted to chronic increased afterload in utero]. 929 54

Cardiovascular disease related to hyperlipidemia is a significant cause of morbidity and mortality in the United States. The benefit of lowering lipid levels in patients with and without cardiovascular disease has been demonstrated in numerous clinical trials. The results of these trials prompted the National Heart, Blood, and Lung Institute to form the Nation Cholesterol Education Panel (NCEP). This panel developed guidelines for identifying and treating lipid disorders. Before starting antilipemic therapy, patients should be evaluated for secondary causes of hyperlipidemia, including disease states and medications. Risk factors for cardiovascular disease should be identified and used to determine the patient's goal low-density lipoprotein level. Regardless of the drug therapy used, the cornerstone treatment for hyperlipidemia is dietary changes. The NCEP recommendation for dietary modification follows a two-step plan to reduce intake of cholesterol and dietary fats. Other nonpharmacologic treatments for hyperlipidemia include exercise, weight reduction for obese patients, reduction of excessive alcohol use, and smoking cessation . Drug therapy should be considered in patients who do not respond to an adequate trial of dietary modifications and lifestyle changes. The principal lipid-lowering agents currently used are the bile acid sequestrants, nicotinic acid, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, and fibric acid derivatives. Estrogen, fish oil, and alcohol also can decrease the risk of developing heart disease. In pharmacoeconomic studies, lipid-lowering drug therapy has been shown to decrease the number of procedures, hospitalizations, and other medical interventions required by patients with cardiovascular disease.
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PMID:Identifying and managing patients with hyperlipidemia. 1017 Mar 3

The isoprenoid metabolic pathway is mainly regulated at the level of conversion of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) to mevalonate, catalyzed by HMG CoA reductase. As estrogens are known to influence cholesterol metabolism, we have explored the potential regulation of the HMG CoA reductase gene promoter by estrogens. The promoter contains an estrogen-responsive element-like sequence at position -93 (termed Red-ERE), which differs from the ERE consensus by one mismatch in each half of the palindrome. A Red-ERE oligonucleotide specifically bound estrogen receptor in vitro and conferred receptor-dependent estrogen responsiveness to a heterologous promoter in all cell lines tested. However, expression of a reporter driven by the rat HMG CoA reductase promoter was induced by estrogen treatment after transient transfection into the breast cancer cell line MCF-7 cells but not in hepatic cell lines expressing estrogen receptor. Estrogen induction in MCF-7 cells was dependent on the Red-ERE and was strongly inhibited by the antiestrogen ICI 164,384. A functional cAMP-responsive element is located immediately upstream of the Red-ERE, but cAMP and estrogens inhibit each other in terms of transactivation of the promoter. Similarly, induction by estrogens was inhibited by micromolar concentrations of cholesterol, likely acting via changes in occupancy of the sterol-responsive element located 70 bp upstream of the Red-ERE. Thus, within its natural context, Red-ERE is able to mediate hormonal regulation of the HMG CoA reductase gene in tissues that respond to estrogens with enhanced cell proliferation, while it is not operative in liver cells. We postulate that this tissue-specific regulation of HMG CoA reductase by estrogens could partially explain the protective effect of estrogens against heart disease.
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PMID:The promoter of the rat 3-hydroxy-3-methylglutaryl coenzyme A reductase gene contains a tissue-specific estrogen-responsive region. 1044 99

The triglyceride (TG) level is one of several lipid parameters that can aid prediction of coronary heart disease (CHD) risk. An elevated plasma TG level is strongly associated with an increased risk of CHD. Hypertriglyceridemia, the second most common dyslipidemic abnormality in hypertensive subjects after increased low-density lipoprotein cholesterol (LDL-C), is defined by the National Cholesterol Education Programme (NCEP) as a fasting TG level of > 2.26 mmol/l (> 200 mg/dl) and is recognised as a primary indicator for treatment in type IIb dyslipidemia. Raised TG levels can be present in individuals at risk for CHD when the total cholesterol is normal. However, not all individuals with raised TG levels have increased risk of CHD. Factors such as: diet, age, lifestyle, and a range of medical conditions, drug therapy and metabolic disorders, can all affect the TG level. In some of these circumstances, other factors protect against the risk of CHD, and can minimise or negate the effect of the risk factors present. Although TG reducing therapy has been shown to be associated with an improved clinical outcome, more research is needed to determine whether this is an independent effect of TG reduction or an effect of normalising the overall lipid profile in hypertriglyceridemic patients. Further trials are required to quantify the clinical benefits of lowering TG to 'target' levels and to confirm targets defined by NCEP-II (shown in Table 1). The role of TG in CHD pathogenesis is thought to involve several direct and indirect mechanisms, such as effects on the metabolism of other lipoproteins, transport proteins, enzymes, and on coagulation and endothelial dysfunction. More research is required to fully elucidate the role of TG, the ways in which it can influence other risk factors and the mechanism of its own more direct role in the atherogenic process. Patients with hypertriglyceridemia have been shown to respond well to dietary control and to the use of lipid lowering drugs such as 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG CoA) reductase inhibitors (known as statins), fibrates and nicotinic acids. However, recent retrospective real-life clinical studies show that only 38% of patients receiving some form of lipid-lowering therapy achieved NCEP-defined LDL-C target levels, demonstrating the need for the use of more aggressive treatment. In hypertriglyceridemic patients, the newer statins, cerivastatin and atorvastatin, have shown comparable efficacy in reducing TG compared with the older statins. Achieving NCEP target lipid levels has been shown to reduce the risk of cardiovascular disease in dyslipidemic individuals, including high-risk patient groups such as those with additional risk factors, existing heart disease, diabetes mellitus and metabolic syndrome. Although the latest clinical studies investigating combination therapies, i.e. dual therapy with both a statin and a fibrate, have demonstrated them to be effective for overall control of lipid parameters and reducing coronary events, it is not yet clear whether this offers any significant advantage over monotherapy. Results from ongoing longer-term end-point clinical studies may provide further information in this area and consequent reviews of primary care management policies for dyslipidemia. Statin monotherapy may be a reliable option for primary care treatment of dyslipidemia (including hypertriglyceridemia).
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PMID:Hypertriglyceridemia: a review of clinical relevance and treatment options: focus on cerivastatin. 1146 48

Twelve children with subaortic stenosis were analysed. Nine of them developed left ventricular outflow obstruction after surgery for congenital heart disease (VSD + IAA, VSD + DORV, VSD + TGA, VSD + CoA) and then developed an isolated form of primary stenosis. Both echocardiographic exams, TTE and TEE were performed in all patients. TTE was sufficient to assess isolated subaortic stenosis. In children after cardiosurgery, TEE was more reliable and provided more detailed visualisation of the stenosis and its relationship to surrounding structures.
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PMID:[The role of transesophageal echocardiography (TEE) in assessment of left ventricular tract obstruction]. 1263 98

Cells contain limited and sequestered pools of Coenzyme A (CoA) that are essential for activating carboxylate metabolites. Some acyl-CoA esters have high metabolic and signalling impact, so control of CoA ester concentrations is important. This and transfer of the activated acyl moieties between cell compartments without wasting energy on futile cycles of hydrolysis and resynthesis is achieved through the carnitine system. The location, properties of and deficiencies in the carnitine acyltransferases are described in relation to their influence on the CoA pools in the cell and, hence, on metabolism. The protection of free CoA pools in disease states is achieved by excretion of acyl-carnitine so that carnitine supplementation is required where unwanted acyl groups build up, such as in some inherited disorders of fatty acid oxidation. Acetyl-carnitine improves cognition in the brain and propionyl-carnitine improves cardiac performance in heart disease and diabetes. The therapeutic effects of carnitine and its esters are discussed in relation to the integrative influence of the carnitine system across CoA pools. Recent evidence for sequestered pools of activated acetate for synthesis of malonyl-CoA, for the synthesis of polyunsaturated fatty acids and for the inhibition of carnitine palmitoyltransferase 1 to regulate fatty acid oxidation is reviewed.
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PMID:Carnitine acyltransferases and their influence on CoA pools in health and disease. 1536 37


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