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)

Screening programmes in child health have evolved on the basis of individual enthusiasm and professional consensus, rather than being based on objective evidence of benefit. Three reviews have been carried out in the UK over the past 10 years. The only programmes which show robust evidence of effectiveness are those for PKU and hypothyroidism. The value of screening for hearing loss and vision defects is widely accepted, but there are many unresolved issues. Programmes for detection of congenital dislocation of the hip, congenital heart disease and growth disturbances are of doubtful value. Early identification of developmental problems is stressed by parents, but screening may not be the best way to achieve this. The UK programme of well-child care places increasing emphasis on promotion of physical and emotional health; screening tests should either be subjected to quality monitoring, or removed from the programme if they cannot fulfil the classic criteria of Wilson and Jungner.
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PMID:Screening in child health. 1036 24

Amiodarone is the most promising drug in the treatment of life-threatening ventricular tachyarrhythmias in patients with significant structural heart disease. The pharmacologic profile of amiodarone is complex and much remains to be clarified about its short- and long-term actions on multiple molecular targets. This article reviews electrophysiologic effects of amiodarone based on previous reports and our own experiments in single cells and multicellular tissue preparations of mammalian hearts. As acute effects, amiodarone inhibits both inward and outward currents. The inhibition of inward sodium and calcium currents (I(Na), I(Ca)) is enhanced in a use- and voltage-dependent manner, resulting in suppression of excitability and conductivity of cardiac tissues especially when stimulated at higher frequencies and in those with less-negative membrane potential. Both voltage- and ligand-gated potassium channel currents (I(K), I(K,Na), I(K,ACh)) are also inhibited at therapeutic levels of drug concentrations. Acutely-administered amiodarone has no consistent effect on the action potential duration (APD). The major and consistent long-term effect of the drug is a moderate APD prolongation with minimal frequency dependence. This prolongation is most likely due to a decrease in the current density of I(K) and I(to). Chronic amiodarone was shown to cause a down-regulation of Kv1.5 messenger ribonucleic acid (mRNA) in rat hearts, suggesting a drug-induced modulation of potassium-channel gene expression. Tissue accumulation of amiodarone and its active metabolite (desethylamiodarone) may modulate the chronic effects, causing variable suppression of excitability and conductivity of the heart through the direct effects of the compounds retained at the sites of action. Amiodarone and desethylamiodarone could antagonize triiodothyronine (T3) action on the heart at cellular or subcellular levels, leading to phenotypic resemblance of long-term amiodarone treatment and hypothyroidism.
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PMID:Amiodarone: ionic and cellular mechanisms of action of the most promising class III agent. 1056 56

Thyroid hormones influence cardiac performance directly and indirectly via changes in peripheral circulation. Little, however, is known about the effect on myocardial oxidative metabolism and its relation to cardiac function and geometry. Patients with a history of thyroidectomy for thyroid cancer present a unique model to investigate the cardiac effects of hypothyroidism. Ten patients without heart disease were investigated in the hypothyroid state and again 4-6 weeks later under euthyroid conditions. Myocardial oxidative metabolism was measured by positron emission tomography with [11C]acetate and the clearance constant k(mono). Cine magnetic resonance imaging was applied to determine left ventricular geometry. A stroke work index (SWI = stroke volume x systolic blood pressure/ventricular mass) was calculated. Then, to estimate myocardial efficiency, a work metabolic index [WMI = SWI x heart rate/k(mono)] was obtained. Compared to hormone replacement, systemic vascular resistance and left ventricular mass were significantly higher in hypothyroidism. Ejection fraction and SWI were significantly lower. Despite an additional reduction of k(mono), the WMI was significantly lower, too. In summary, cardiac oxygen consumption is reduced in hypothyroidism. This reduction is associated with increased peripheral resistance and reduced contractility. Estimates of cardiac work are more severely suppressed than those of oxidative metabolism, suggesting decreased efficiency. These findings may provide an explanation for development or worsening of heart failure in hypothyroid patients with preexisting heart disease.
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PMID:Effect of thyroid hormones on cardiac function, geometry, and oxidative metabolism assessed noninvasively by positron emission tomography and magnetic resonance imaging. 1084 59

Subclinical hypothyroidism (SH) is common, especially among elderly women. There is no clear evidence to date that SH causes clinical heart disease. However, mild thyroid gland failure, evidenced solely by elevation of the serum thyrotropin (TSH) concentration, may be associated with increased morbidity, particularly for cardiovascular disease, and subtly decreased myocardial contractility. In SH, both cardiac structures and function remain normal at rest, but impaired ventricular function as well as cardiovascular and respiratory adaptation to effort may become unmasked during exercise. These changes are reversible when euthyroidism is restored. Flow-mediated vasodilatation, a marker of endothelial function, is significantly impaired in SH, and decreased heart rate variability, a marker of autonomic activity, suggests hypofunctional abnormalities in the parasympathetic nervous system. SH does result in a small increase in low-density lipoprotein (LDL) cholesterol (C) and a decrease in high-density lipoprotein (HDL)-C, changes that enhance the risk for development of atherosclerosis and coronary artery disease (CAD). After coronary revascularization, a trend toward higher rates of chest pain, dissection, and reocclusion has been noted in SH subjects. Smoking may contribute to the high incidence of SH and may aggravate its metabolic effects. Subjects with SH with marked TSH elevation and high titers of thyroid autoantibodies are at higher risk of unnoticed progression to overt hypothyroidism. Especially women over 50 years with TSH levels greater than 10 mU/L and smoking habits have the highest risk for cardiovascular complications. The magnitude of the lipid changes and the subtle impairment of left ventricular function and cardiopulmonary exercise capacity in SH may justify use of hormone replacement. Early levothyroxine (LT4) treatment in SH may reduce the C level by an average of 8% and normalize all metabolic effects in smokers, nevertheless, in some patients, LT4 therapy may exacerbate angina pectoris or an underlying cardiac arrhythmia. Longitudinal follow-up to define the actual cardiovascular disease risk associated with SH is warranted.
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PMID:Cardiovascular and atherogenic aspects of subclinical hypothyroidism. 1101 11

The significance of subclinical hypothyroidism in regard to ensuing hyperlipidemia remains unclear. Because an unfavorable lipid profile would provide a possible explanation for the reported association of coronary-heart disease with this syndrome, we have evaluated the relationship of thyrotropin (TSH) with total cholesterol, low-density-lipoprotein (LDL) cholesterol, and triglycerides in patients with normal thyroid function (n = 4886) as well as subclinical (n = 1055) and manifest (n = 92) hypothyroidism. Serum concentrations of LDL cholesterol were similar in euthyroid persons (134+/-39 mg/dL) and in patients with subclinical hypothyroidism (137+/-40 mg/dL) but were higher (178+/-70 mg/dL, p < 0.01) in overt hypothyroidism. Within the group of subjects with subclinical hypothyroidism there was no apparent relationship between serum concentrations of TSH ranging from 4.0 to 49.0 microU/mL and concentrations of LDL cholesterol. Thus, there is no "threshold value" of TSH in these patients per se necessitating substitution therapy with thyroxine.
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PMID:Low-density lipoprotein cholesterol in subclinical hypothyroidism. 1112 26

Our objective was to investigate whether a relationship exists among maternal thyroid function, nausea and vomiting of pregnancy, and congenital heart disease. A Medline search from 1966 to the present was conducted to look for reports on the existence of this relationship. The results were supplemented by abstract searches and personal communication with relevant authors. Our search found independent evidence that maternal hyperthyroidism is related to increased rates of nausea and vomiting of pregnancy, which in turn is significantly related to a decrease in the incidence of congenital heart disease. Early evidence indicates that the converse may be true: maternal hypothyroidism and thyroid replacement therapy are associated with an increase in congenital heart disease in children. The potential relationship between maternal thyroid function, nausea and vomiting of pregnancy, and thyroid replacement therapy needs further study. We propose a case-control study of children presenting for echocardiography to elicit specific information regarding the pregnancy.
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PMID:Hypothetical framework for a relationship between maternal thyroid function, nausea and vomiting of pregnancy, and congenital heart disease. 1135 68

The Johanson-Blizzard Syndrome (JBS) is an autosomal recessive disorder with a characteristic phenotype, including dwarfism, a beaked nose with aplastic alae nasi, a high forehead, mid-line ectodermal scalp defects with sparse hair and absent eyelashes/eyebrows, prominent scalp veins, low set ears, a large anterior fontanelle, micrognathia, thin lips, absent permanent dentition and microcephaly. In addition to the characteristic facial features, associated conditions include congenital heart disease, exocrine/endocrine pancreatic dysfunction, hypothyroidism, hypopituitarism, mental retardation, sensorineural hearing loss and vesico-ureteral reflux. A case is presented and the potential anaesthetic implications of this syndrome are discussed.
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PMID:Perioperative care of the child with the Johanson-Blizzard syndrome. 1253 44

Using noninvasive imaging, we have previously demonstrated that myocardial efficiency is impaired in hypothyroidism and improves after establishing euthyroid conditions. Little is known about the effects of abnormally elevated thyroid hormone exposure on cardiac metabolic performance. We studied 10 patients without evidence of heart disease in mild hyperthyroidism, and after therapy under euthyroid conditions. Cardiac oxidative metabolism was quantified by positron emission tomography with [(11)C]acetate. Left ventricular geometry was determined by cine magnetic resonance imaging. Myocardial efficiency, defined by the relation between work and oxygen consumption, was estimated using the work metabolic index [WMI = stroke volume * systolic blood pressure * heart rate/(oxidative metabolism * ventricular mass)]. In hyperthyroidism, heart rate and cardiac output were expectedly higher. Peripheral vascular resistance was reduced. Differences of blood pressure, stroke volume, and ventricular mass were not observed. Oxidative metabolism was significantly higher, but WMI was not different from the euthyroid state. In summary, while improvement of efficiency through thyroid hormone substitution was observed previously in hypothyroidism, our data in mild hyperthyroidism suggest an increase of oxygen consumption, paralleled by an increase of work. Thus, moderately elevated thyroid hormone levels neither result in further increase nor in reduction of cardiac metabolic performance.
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PMID:Cardiac oxidative metabolism, function, and metabolic performance in mild hyperthyroidism: a noninvasive study using positron emission tomography and magnetic resonance imaging. 1285 14

This is a descriptive and follow-up study of the efficacy of radioiodine (131I) in the treatment of hyperthyroidism in Nigerian patients, and is aimed at creating awareness about the therapy amongst medical practitioners in the West African sub-region. Twenty-two patients (13 female, 9 males) were seen with clinical and biochemical features of thyrotoxicosis, and were treated with 131I between 1991 and 1999. The age range was 31 to 60 years, with a mean age of 44.2 +/- 1.8 years. The indications for 131I therapy were diverse and included its use as a first-line treatment for Graves' disease, thyrotoxic heart disease, recurrent thyrotoxicosis and failed antithyroid drug therapy. An incremental fixed-dose regimen was used in successive years, for different batches of patients. The duration of follow-up ranged from two months to nine years with a mean duration of 3.6 +/- 0.5 years. Three patients achieved euthyroidism, two patients needed a re-treatment with 131I because of persistent Hyperthyroidism. Nine patients developed hypothyroidism between two to 30 months of receiving 131I therapy. While seven other patients defaulted soon after the treatment and one patient who also had type 1 diabetes mellitus suffered a sudden death after two months. In conclusion, our experience revealed similar outcomes as have been reported by other workers. Radioactive iodine was found to be a safe and an effective treatment for hyperthyroidism in Nigerian patients, but a high rate of default precludes adequate long-term follow-up.
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PMID:Experience in the use of radioactive iodine therapy for hyperthyroidism in Nigerian patients. A study of twenty-two patients. 1500 98

An extract of the plant Coleus forskohlii has been used for centuries in Ayurvedic medicine to treat various diseases such as hypothyroidism, heart disease, and respiratory disorders. Additionally, complex herbal mixtures containing this extract are gaining popularity in United States for their putative "fat-burning" properties. The active ingredient in C. forskohlii extract is the diterpene compound forskolin. Forskolin is a widely used biochemical tool that activates adenyl cyclase, thereby increasing intracellular concentration of cAMP and thus activating the protein kinase A (PKA) signal transduction pathway. We show herein that both forskolin and its nonadenyl cyclase-activating analog 1,9 dideoxyforskolin induce CYP3A gene expression in primary hepatocytes by functioning as agonists of the pregnane X receptor (PXR). We show that activation of PKA signaling potentiates PXR-mediated induction of CYP3A gene expression in cultured hepatocytes and increases the strength of PXR-coactivator protein-protein interaction in cell-based assays. Kinase assays show that PXR can serve as a substrate for catalytically active PKA in vitro. Our data provide important insights into the molecular mechanism of both the PKA-dependent and -independent effects of forskolin on the expression of drug-metabolizing enzymes in liver. Finally, our data suggest that herbal therapy with C. forskohlii extract should be approached cautiously due to the potential for herb-drug interactions in patients on combination therapy.
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PMID:Induction of drug metabolism by forskolin: the role of the pregnane X receptor and the protein kinase a signal transduction pathway. 1545 37


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