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

Angiotensin II receptor blockers (ARBs) represent a new class of effective and well tolerated orally active antihypertensive agents. Recent clinical trials have shown the added benefits of ARBs in hypertensive patients (reduction in left ventricular hypertrophy, improvement in diastolic function, decrease in ventricular arrhythmias, reduction in microalbuminuria, and improvement in renal function), and cardioprotective effect in patients with heart failure. Several large long-term studies are in progress to assess the beneficial effects of ARBs on cardiac hypertrophy, renal function, and cardiovascular and cerebrovascular morbidity and mortality in hypertensive patients with or without diabetes mellitus, and the value of these drugs in patients with heart disease and diabetic nephropathy. The ARBs specifically block the interaction of angiotensin II at the AT1 receptor, thereby relaxing smooth muscle, increasing salt and water excretion, reducing plasma volume, and decreasing cellular hypertrophy. These agents exert their blood pressure-lowering effect mainly by reducing peripheral vascular resistance usually without a rise in heart rate. Most of the commercially available ARBs control blood pressure for 24 h after once daily dosing. Sustained efficacy of blood pressure control, without any evidence of tachyphylaxis, has been demonstrated after long-term administration (3 years) of some of the ARBs. The efficacy of ARBs is similar to that of thiazide diuretics, beta-blockers, angiotensin-converting enzyme inhibitors or calcium channel blockers in patients with similar degree of hypertension. Higher daily doses, dietary salt restriction, and concomitant diuretic or ACE inhibitor administration amplify the antihypertensive effect of ARBs. The ARBs have a low incidence of adverse effects (headache, upper respiratory infection, back pain, muscle cramps, fatigue and dizziness), even in the elderly patients. After the approval of losartan, five other ARBs (candesartan cilexetil, eprosartan, irbesartan, telmisartan, and valsartan) and three combinations with hydrochlorothiazide (irbesartan, losartan and valsartan) have been approved as antihypertensive agents, and some 28 compounds are in various stages of development. The ARBs are non-peptide compounds with varied structures; some (candesartan, losartan, irbesartan, and valsartan) have a common tetrazolo-biphenyl structure. Except for irbesartan, all active ARBs have a carboxylic acid group. Candesartan cilexetil is a prodrug, while losartan has a metabolite (EXP3174) which is more active than the parent drug. No other metabolites of ARBs contribute significantly to the antihypertensive effect. The variation in the molecular structure of the ARBs results in differences in the binding affinity to the receptor and pharmacokinetic profiles. The differences observed in lipid solubility, absorption/distribution, plasma protein binding, bioavailability, biotransformation, plasma half-life, and systemic elimination influence the time of onset, duration of action, and efficacy of the ARBs. On the basis of the daily mg dose, the antihypertensive potency of the ARBs follows the sequence: candesartan cilexetil > telmisartan approximately = losartan > irbesartan approximately = valsartan > eprosartan. After oral administration, the ARBs are rapidly absorbed (time for peak plasma levels = 0.5-4 h) but they have a wide range of bioavailability (from a low of 13% for eprosartan to a high of 60-80% for irbesartan); food does not influence the bioavailability, except for valsartan (a reduction of 40-50%) and eprosartan (increase). A limited dose-peak plasma levels/areas under the plasma level-time curve proportionality is observed for some of the ARBs. Most of these drugs have high plasma protein binding (95-100%); irbesartan has the lowest binding among the group (90%). The steady-state volumes of distribution vary from a low of 9 L (candesartan) to a high of 500 L (telmisartan). (ABSTRACT TRUNCATE
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PMID:Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension. 1085 85

Genetic hemochromatosis is an autosomal recessive disease, characterized by an increased iron absorption, leading to progressive iron overload. The fully expressed phenotype comprises fatigue, skin pigmentation, liver disease with hepatomegaly, cirrhosis and hepatocellular carcinoma, and diabetes. Arthralgias are frequent, cardiopathy or impotence may occur. This presentation is now unfrequent with earlier diagnosis, and patients are often asymptomatic--with only biochemical expression--or pauci-symptomatic (mild fatigue, arthralgias or increased transaminases). Transferrin saturation is always increased. Serum ferritin is proportional to iron burden. Diagnosis is now easy, since most patients are homozygote for the C282Y mutation of the HFE gene. Liver biopsy can be useful to quantify iron overload and assess liver fibrosis. The disease can be lethal due to liver disease, carcinoma or heart disease, but life expectancy goes to normal if patients are treated before the occurrence of cirrhosis. Treatment relies on regular venesections. Familial screening is essential.
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PMID:[Diagnosis and treatment of genetic hemochromatosis]. 1086 97

The incidence of AF, the most common sustained arrhythmia in clinical practice, increases with age and coronary artery disease, hypertension and valvular heart disease are common underlying substrates; however, occasionally, AF may occur without any underlying heart disease. The most widely accepted theory of its mechanism is Moe's multiple wavelet hypothesis, although recent studies are helping to shed light on other mechanisms, including the focal origin of AF in some patients. Most patients experience palpitations, but fatigue, dyspnoea, and dizziness may also occur. Therapy includes prevention of thromboembolism, control of rate, and restoration and maintenance of sinus rhythm. The risks and benefits of each treatment modality need to be assessed according to each patient's circumstances. Unlike other arrhythmias, there is still no highly successful therapy for treating AF. However, significant advances are being made using non-pharmacological approaches to either prevent or cure this troublesome arrhythmia.
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PMID:Atrial fibrillation: epidemiology, mechanisms and management. 1089 90

Car driving, airplane piloting and underwater activities by subjects with heart disease may cause sudden incapacitation leading to the loss of the safety margins necessary to avoid accidents. In the case of car driving and airplane piloting the risk affects, not only the driver or pilot, but also passengers and/or bystanders within an accident zone. In the case of diving the risk resides basically in the loss of control of the vital support mechanisms necessary in a very hostile medium. This document reviews the possible causes of unexpected incapacitation, with or without loss of consciousness, in the light of the pathophysiologic consequences of fatigue, hypoxia, stress or barotrauma posed by each activity. Detailed recommendations are made for limiting driving, piloting and diving, based on official Spanish and European regulations and the addresses of specialized centers are provided for consultation. Moreover, recommendations for airplane travel for patients with heart disease are indicated.
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PMID:[Guidelines of the Spanish Society of Cardiology for car driving, airplane flying,and underwater activities in subjects with heart disease]. 1128 53

Chronic obstructive pulmonary disease (COPD) is a leading cause of death, and constitutes a major medical and an increasing economic problem for acute and long term care. A low level of irreversible airway obstruction when in stable condition, hypercapnia, hypoxia, the presence of comorbid heart disease, right ventricular failure, and low serum albumin are the main factors related to risk of exacerbations. Bronchial infections, bronchospasm, left ventricular failure, pneumonia, pneumothorax and thromboembolism are described as the most frequent relapsing causes of COPD. During exacerbation, the inflammatory process, the ventilation/perfusion (V'A/Q') mismatching, an increased airflow resistance and dynamic hyperinflation (PEEPidyn) expose the respiratory muscles to the risk of fatigue, eventually leading to ventilatory pump failure and rising hypercapnia. Prevention of exacerbations and subsequent hospitalisations may be obtained with careful rehabilitation programs, a strict drug protocol, long term oxygen therapy and sometimes using home noninvasive mechanical ventilation (NMV). During exacerbation proper management of infection and lung mechanics derangement has to be adopted using an accurate assessment of severity and standardized treatment protocols. Patient history and examination and functional tests are beneficial to decide how and where to treat these patients. Mechanical ventilation (possibly noninvasive) may be required to reverse the acute episode. The aims of all these procedures remain: i) to prolong length and quality of life; ii) to save costs. Both hospital and post-discharge mortality of exacerbated COPD remain high while quality of life appears to be poor. Future studies will elucidate the relation between number and severity of exacerbations and prognosis.
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PMID:Exacerbations of COPD: predictive factors, treatment and outcome. 1149 3

A 10-year-old boy with a medical history of fatigue became nauseous, short of breath and cyanotic within 24 hours after a frightening incident. He was successfully resuscitated after a cardiac arrest. A CT scan revealed a ruptured aneurysm of the ascending aorta. During emergency surgery the ascending aorta and aortic arch were replaced with a 22 mm synthetic graft. No postoperative complications occurred. There was no associated trauma, syphilis, collagen diseases (Marfan's syndrome, Ehlers-Danlos syndrome), congenital heart disease or autoimmune disease. The cause of the aneurysm and rupture remain unclear.
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PMID:[Rupture of thoracic aneurysm in a 10-year old boy]. 1177 Feb 68

Well-known adverse effects of amisulpride include nausea, insomnia or tiredness, gastrointestinal, extrapyramidal and endocrine symptoms. Cardiac disorders, however, appear to be an extremely rare complication of the drug. Only a few case reports on this complication have been published so far, which deal with QT prolongation, hypotension, hypertension and palpitations. Bradycardia has not yet been mentioned. Here, we will report on a case of asymptomatic bradycardia that developed subsequent to therapeutic doses of amisulpride in a 25-year-old male patient with chronic paranoid-hallucinatory schizophrenia. The patient had been rehospitalized for an acute exacerbation of the psychosis. When the patient failed to respond at the beginning of hospitalization, the treatment was changed from clozapine to amisulpride. After a complete switchover to amisulpride, the patient's ECG showed sinus bradycardia and QT prolongation. When the daily dose of amisulpride was reduced from 800 mg/d to 600 mg/d, the patient's ECG quickly normalized (including blood pressure and pulse rate) within a few days. The patient did not report any cardiovascular-related complaints. Since the cardiovascular-specific diagnostics did not yield any indicative results, bradycardia may be a rare complication of amisulpride treatment.
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PMID:Asymptomatic bradycardia associated with amisulpride. 1177 48

Many countries in Asia, Africa, Latin America, and the Caribbean offer substantial tax breaks to foreign corporations that set up shops in free-trade zones and waive environmental regulations and repress trade unions to further induce this practice. Workers in these shops--mainly women--perform repetitive machine-based motions, are exposed to toxic chemicals and unsafe equipment, and face dangerously high production quotas. Health problems caused by these working conditions include headache and dizziness, fatigue, anemia, forgetfulness, stomach pains, respiratory problems, hypertension, heart disease, and allergies. Water and air pollution and dumping of hazardous waste affect the health of entire communities. Since free-trade zones are a permanent feature of the global economy, organizing to protect workers and communities assumes critical importance. Groups such as the Border Committee of Women Workers in Mexico are providing workers with skills and support to make demands such as better treatment of pregnant workers. International labor, environmental, and public health advocates can support such efforts by providing assistance to worker-controlled organizations and pressuring governments to enforce laws intended to protect workers and their communities.
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PMID:Globalization causes a world of health problems. 1234 7

Psychological depression is shown to be associated with several aspects of coronary artery disease (CAD), including arrhythmias, myocardial infarction, heart failure and sudden death. The physiological mechanisms accounting for this association are unclear. Hypothalamic-pituitary-adrenal dysregulation, diminished heart rate variability, altered blood platelet function and noncompliance with medial treatments have been proposed as mechanisms underlying depression and cardiovascular disease. Recent evidence also suggests that reduced baroreflex sensitivity, impaired immune function, chronic fatigue and the co-morbidity of depression and anxiety may be involved in the relationship between depression and cardiovascular dysregulation. An experimental strategy using animal models for investigating underlying physiological abnormalities in depression is presented. A key to understanding the bidirectional association between depression and heart disease is to determine whether there are common changes in brain systems that are associated with these conditions. Such approaches may hold promise for advancing our understanding of the interaction between this mood disorder and CAD.
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PMID:Biological mechanisms in the relationship between depression and heart disease. 1266 98

The objectives of this study were twofold: (1) to explore and compare the symptom experience of seriously ill hospitalized cancer and noncancer patients near the end of life using the Memorial Symptom Assessment Scale (MSAS) and (2) to determine if the MSAS is a valid and useful measure of symptom distress for patients with noncancer conditions. This was a prospective cohort study of hospitalized patients with end-stage congestive heart disease, chronic pulmonary disease, cirrhosis, or metastatic cancer. Eligible patients were interviewed to ascertain symptom prevalence, severity and distress using the MSAS and levels of fatigue using the Piper Fatigue Scale (PFS). Sixty-six patients with metastatic cancer and 69 patients with end-stage disease were enrolled in the study. There was a significant difference in the prevalence of selected physical symptoms, but not psychological symptoms, between cancer and noncancer patients. There were no significant differences in symptom distress scores, a computed score of frequency, severity and distress, if the symptom was present. In both groups the principal components factor analysis with varimax rotation yielded one factor comprising psychological symptoms and a second factor comprising three subgroups of physical symptoms. Internal consistency was high for the psychological subscale (Cronbach alpha coefficients of 0.85 for the cancer group and 0.77 for the noncancer group) and for the physical subscale groupings, with coefficients ranging between 0.78 to 0.87. The symptom scores were significantly correlated with perceptions of fatigue. These findings show that both seriously ill cancer and noncancer patients experience symptom distress, and that the MSAS seems to be a reliable measure of symptom distress in noncancer patients, as well as with cancer patients.
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PMID:Measuring the symptom experience of seriously ill cancer and noncancer hospitalized patients near the end of life with the memorial symptom assessment scale. 1272 39


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