Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of hypertension in the elderly has so far mainly been based on clinical judgment and very few large controlled trials. During the last year several large new trials have been published, the so-called STOP-Hypertension, SHEP, and MRC trials. All have shown that drug treatment of hypertension in the elderly (65-85 years) with permanent diastolic hypertension or isolated systolic hypertension reduces stroke incidence. Most patients have needed combined drug treatment with diuretics and beta-blockers. When thiazide diuretics are used, serum potassium should be followed very closely and most likely amiloride should be added to the thiazide therapy, since this was done both in the STOP and the MRC trials. Since many elderly patients with hypertension suffer from other diseases that might represent contraindications to thiazide diuretics or beta-blockers, the choice of drug must be made after careful clinical evaluation. With the newer classes of antihypertensive agents (calcium antagonists, ACE inhibitors and alpha-blockers) side effects are probably seen less often, but long-term data on morbidity and mortality are still lacking.
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PMID:Treatment of hypertension in the elderly--what have we learned from the recent trials? 129 75

This study reports the outcome of POMB/ACE (cisplatin, vincristine, methotrexate, bleomycin, actinomycin D, cyclophosphamide, etoposide) chemotherapy in 53 male patients with metastatic non-seminomatous germ cell tumour (NSGCT) treated between 1983 and 1989 in one centre. The overall complete response (CR) rate was 62% [95% confidence interval (CI) 49-75%), and for patients with large or very large volume disease (L/VL, MRC criteria), the CR rate was 56% (95% CI 41-71%). The overall 5 year survival was 61%, and for L/VL volume disease 67%. Comparison with previous studies suggests that POMB/ACE chemotherapy is not superior to BEP, even in patients with adverse prognostic factors. Increased average relative dose intensity and increased relative dose intensity of cisplatin over the first seven courses were not associated with improved survival. However, in patients receiving a relative dose intensity of etoposide greater than or equal to 0.75, survival at 5 years was significantly improved compared with those in whom this parameter was less than 0.75 (79% vs. 44%, P less than 0.05), suggesting that dose intensity of etoposide may be an important determinant of outcome in the chemotherapy of metastatic NSGCT.
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PMID:POMB/ACE chemotherapy in non-seminomatous germ cell tumours: outcome and importance of dose intensity. 137 36

The large multicenter trials of treatment in mild to moderate hypertension have shown unequivocally that the risk of stroke is reversed. The impact of treatment on ischemic heart disease is more debatable. Since there is no discontinuity in the risk of different levels of blood pressure, any advice about the level of pressure to treat must be arbitrary. The British Hypertension Society Guidelines recommend a sustained diastolic pressure of 100 mmHg or more over a 3- to 4-month period. This empirical advice is based upon subgroup analysis of the MRC and Australian Therapeutic Trials that suggests most of the benefit in treating the mildest degrees of hypertension occur in this group of patients. The role of newer classes of agent, such as ACE inhibitors or calcium-channel blockers, cannot be fully assessed in the absence of proper end-point trials. Whilst reasons for using these agents as first-line therapy have been put forward, these remain speculative in the absence of such trials. The much greater cost of newer agents in the context of universally cost-constrained health services also has to be borne in mind before recommending their widespread use as first-line therapy.
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PMID:The level at which blood pressure should be treated. 180 96

Steroids are used in progressive lung sarcoid despite arguments that spontaneous remission occur and therapy may not alter outcome. We studied a unique group of 6 patients with dyspnea and advancing pulmonary sarcoid, who had documented untreated progressive disease for 6.8 +/- 2.4 years. Raised SACE, Ga 67 lung uptake, and lymphocyte counts in lung lavage fluid indicated continued active alveolitis. After 3-6 months on steroid, MRC dyspnea grade fell from 2.5 to 0.3 and FVC, FEV, and DLCO increased by 36%, 27% and 16% respectively. This was associated with a fall in small opacity profusion scores on x-ray lung uptake of Ga 67 and serum ACE. These improvements were sustained for the duration of follow up (mean 22 months). These data show that steroids can alter the natural history of progressive sarcoid and reversible alveolitis may coexist with established fibrosis.
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PMID:Evidence that steroids alter the natural history of previously untreated progressive pulmonary sarcoidosis. 357 16

There is ample evidence that antihypertensive therapy prevents strokes, congestive heart failure, and other blood pressure-related complications, but most trials have failed to show a reduction in coronary events and mortality. Recently, the Systolic Hypertension in the Elderly Program (SHEP) showed a reduction in MIs and other coronary events in older patients with moderate to severe ISH. Cardiovascular mortality was also reduced and there was a trend toward a reduction in coronary events in the Swedish STOP-Hypertension Trial and the British MRC Trial in Older Patients. These studies have in common the use of diuretics and/or beta blockers. Although there are no similar long-term data with calcium channel blockers and ACE inhibitors, they will be the drugs of choice for many patients, based on individual responses and accompanying medical conditions.
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PMID:First-line therapy for hypertension: different patients, different needs. 790 5

Hypertension occurs in 50% of the elderly persons in industrialized societies. This disorder of the regulation of the arterial blood pressure has different manifestations in different age groups. The young hypertensive usually has an increase in cardiac output and a normal peripheral vascular resistance. The elderly patient with hypertension exhibits a decreased cardiac output and an increased peripheral vascular resistance. In the elderly hypertensive there is a progressive anteriolar narrowing and there is hardening of the largest arteries. The vascular disease that contributes to the hypertension in the elderly also causes hypoperfusion of the target organs. During the aging process there is a decrease in cardiac output, glomerular filtration rate, vital capacity, renal plasma flow and maximal cardiac rate. There are changes in the kidneys and the liver that influence the way different medications are handled by the body. The main findings of the Australian, EWPHE, Coope & Warrender, SHEP, STOP-HYP and MRC studies of hypertension in the elderly have been summarized. The intervention studies have proven that the treatment of hypertension in the elderly patient is efficacious and decreases the mortality and morbidity due to coronary and cerebrovascular events. The pharmacologic agents available for the treatment of hypertension in the elderly are the diuretics, beta blockers, vasodilators, calcium-channel blockers, adrenergic blockers and angiotensin converting enzyme inhibitors. The morbidity and mortality benefits derived from antihypertensive trials are greater for the older than for the younger patients. The pharmacologic antihypertensive agents to be used in older patients will also depend upon the presence or not of associated illnesses in which some agents might be harmful or contraindicated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Hypertension in old age]. 858 23

Diuretics were used in most of the major trials that demonstrated that lowering the blood pressure reduced cardiovascular morbidity and mortality. Nevertheless in the second half of the eighties, there were misgivings about the widespread use of thiazide diuretics, driven in part by the relative failure of the large trials to reduce myocardial infarction-to the extent predicted by large scale epidemiological studies. There was much attention on metabolic side effects of thiazide diuretics including dyslipidaemia, glucose intolerance, hypokalaemia, hyperuricaemia, and then microalbuminuria particularly in diabetic subjects. These issues were current when JNC (IV) (1988) and the WHO-ISH guidelines (1989) were being written. Three major clinical trials SHEP, STOP and MRC published in the early nineties established that thiazide diuretics alone, or in combination with beta blockers, did reduce cardiovascular morbidity and mortality in elderly subjects with hypertension. All guidelines published since 1993 include diuretics among the first line drugs. Possibly the most important factor in the restoration of diuretics has been the use of progressively lower doses that minimise the metabolic side effects. Diuretics are effective as monotherapy in the treatment of mild essential hypertension and of isolated systolic hypertension in elderly subjects. They are very useful in combination with beta blockers or with ACE inhibitors. They should be avoided in patients with gout and should not be used as first line drugs in patients with diabetes. They should only be used with caution in young obese subjects with dyslipidaemia and increased risk of coronary artery disease, facing many decades of treatment for hypertension. However there is no doubt that diuretics are effective, cheap and have a central role in the control of hypertension in all communities around the world.
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PMID:[Role of diuretics in the treatment of hypertension: from large controlled trials to international guidelines]. 895 12

Over the past decade, national and international guidelines have proposed beta-blockers to be used on an equal footing with diuretics for initial therapy of hypertension. This preferred status was supposedly based on evidence documenting a reduction in morbidity and mortality with beta-blocker therapy in hypertension. We systematically analyzed all available outcome studies and found no evidence that beta-blocker based therapy, despite lowering blood pressure, reduced the risk of heart attacks or strokes. Despite the inefficacy of beta-blockers, the incidence of adverse effects is substantial. In the MRC study, for every heart attack or stroke prevented, three patients withdrew from atenolol because of impotence, and another seven withdrew because of fatigue. Thus the risk/benefit ratio of beta-blockers is characterized by lack of efficacy and multiple adverse effects. Given that many thorough, prospective, randomized trials attest to efficacy and safety of diuretics, calcium antagonists, ACE inhibitors, and angiotensin receptor inhibitors, the time has come to admit that beta-blockers should no longer be considered appropriate for first-line therapy in uncomplicated hypertension.
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PMID:beta-Blockers in hypertension-the emperor has no clothes: an open letter to present and prospective drafters of new guidelines for the treatment of hypertension. 1455 68

Management of hypertension in the elderly should take into account, in particular, the possible negative impact of antihypertensive drugs on the patient's quality of life, the deterioration of which may result in a loss of independence and reduced treatment compliance. Quality of life is recognised as a multifactorial variable and can be subdivided into different domains (symptomatic well-being, emotional, physical, work-social, cognitive and life satisfaction), which are generally explored by means of specific questionnaires or scales. When evaluating elderly patients with hypertension, it is necessary to pay particular attention to specific domains such as symptomatic well-being, cognitive function, activity and sexual function, which have already been diminished by the age itself and the disease. The results of some large trials that specifically evaluated the quality of life effects of long-term therapy of hypertension in older people (Medical Research Council's [MRC] Trial of Hypertension in Older Adults, Systolic Hypertension in the Elderly Program [SHEP], Systolic Hypertension in Europe [Syst-Eur], Study on COgnition and Prognosis in the Elderly [SCOPE]) have shown that antihypertensive treatment as a whole either had no negative impact on quality of life, or even produced some improvement. The question whether some classes of antihypertensive agents are more beneficial or harmful than others in terms of quality-of-life effects remains largely unanswered. Results from long-term trials suggest that treatment with diuretics is not associated with adverse effects on quality of life. Nevertheless, chlortalidone and other diuretics have been more often associated with sexual dysfunction in men, including decreased libido, erectile dysfunction and difficult ejaculation, than other drug classes. Nonselective lipophilic beta-adrenoceptor antagonists, such as propranolol, have been reported to exert some negative effect on quality of life and have been associated with depression, impairment of memory function and adverse effects such as erectile problems. A less unfavourable impact has been described with beta(1)-adrenoceptor antagonists and those with vasodilating properties. Calcium channel antagonists have generally been associated with a positive effect on quality of life, although some trials have shown high rates of adverse effects and withdrawals, particularly with first-generation dihydropyridines. Concern has also been raised about the potential for adverse cognitive effects associated with the use of calcium channel antagonists, but studies on this topic are not univocal. ACE inhibitors have usually been reported to exert favourable effects on quality of life. These drugs seem to be effective in maintaining, or even improving, cognitive function through mechanisms other than blood pressure control. In addition, a number of studies reported favourable impact of ACE inhibitors on sexual function. Angiotensin II receptor antagonists have been associated with good tolerability and low withdrawal rate. They have been demonstrated not to interfere with or even improve cognitive function as well as sexual performance. Although no class of antihypertensive agents presents a clearly superior effect over the others in terms of quality of life, the current impression is that ACE inhibitors and angiotensin II receptor antagonists may offer some advantage, at least in regard to effects on cognitive function and sexual activity.
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PMID:Effect of antihypertensive agents on quality of life in the elderly. 1508 40

Despite a high cure rate in men with testicular cancer, some men in the poor-prognosis group have a less favourable outcome. Poor-prognosis non-seminomatous germ-cell tumours (NSGCT) are defined as those with high tumour markers, non-pulmonary visceral metastases or a mediastinal primary site at presentation. When treated with standard chemotherapy regimens, such as bleomycin, etoposide and cisplatin (BEP), cure rates of less than 50% have been achieved in an international pooled analysis. Some strategies aimed at improving results include the use of multi-agent regimens (e.g. POMB/ACE), intensive-induction chemotherapy (e.g. CBOP/BEP), new chemotherapy drugs, such as ifosfamide, gemcitabine, oxaliplatin, paclitaxel, high-dose chemotherapy, including autotransplantation. To date, no schedule has been proven to be better than standard BEP in randomised trials. We will review the published data relating to first-line and salvage treatment of poor-prognosis NSGCT. To advance the management of this disease, physicians treating poor-prognosis disease are urged to support multi-centre trials, such as the recently launched MRC TE23 study comparing BEP and CBOP/BEP.
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PMID:The management of poor-prognosis, non-seminomatous germ-cell tumours. 1623 42


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