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Biomedical subjects

A Fletcher

Publications and source records attributed to A Fletcher.

At least 145 records · Page 8Linked to original sources
PubMed1994

Epidemiology of hypertension in the elderly.

DISTRIBUTION: Blood pressure tends to rise with increasing age. Six to eight per cent of people aged 60-69 years, and about 12-16% of those aged 70-79 years, are estimated to need treatment for raised systolic and diastolic blood pressures. DETERMINANTS: It seems likely that the rise in blood pressure with increasing age is partly explained by the determinants of blood pressure, such as sodium intake, body weight, physical exercise and alcohol consumption. MORTALITY: There is a linear relationship between the level of diastolic or systolic blood pressure and the risk of stroke or coronary heart disease. However, the relationship between blood pressure and mortality in later life may be obscured if concurrent illness lowers blood pressure; low blood pressure by itself may not be a risk factor for mortality. TREATMENT: Randomly allocated trials have consistently shown that the treatment of hypertension in men and women over 60 years of age reduces the incidence of stroke by about 40%, and some trials have also shown reductions in coronary events.

Aged↗
PubMed1994

Economics of hypertension control: a statement by the World Hypertension League.

While expenditures for hypertension are on the increase in developed countries, and potentially also in the developing world, resource constraints, even in the most affluent countries, need to consider hypertension control in the context of other demands of society. This position paper sums up the key aspects of the debate: problems of estimating the economic burden of hypertension and hypertension-related disease; the use of economic models; and opportunities for containing the costs. Direct healthcare costs of hypertension are amenable to calculations; but more information is needed on the population attributable risk of hypertension in various countries, indispensable to estimate the part of hypertension in the burden of stroke and heart disease. The population and the high-risk approach to hypertension control also have economic consequences; these may vary in different societies and need to be assessed to ensure appropriate allocation of resources. Cost containment can be achieved i.a. by more selective diagnostic investigations, and by opting for cheaper drugs, though the choice of treatment is difficult owing to uncertainties in the quality-of-life estimates. The economics of hypertension is a complex field, calling for continued research and monitoring.

Cost of Illness↗
PubMed1994

Parental monitoring and peer influences on adolescent substance use.

OBJECTIVE: To examine the joint influences of parental monitoring and peer influence on adolescent substance use over time. SUBJECTS: 6500 adolescents attending six high schools in Wisconsin and northern California. DESIGN: Longitudinal study. RESULTS: Parental monitoring was negatively associated with substance use, whereas the more involved an adolescent's peers were in substance use, the more likely he or she also was to use drugs and alcohol. Effects of monitoring and peer coercion were strongest for boys and girls at the transition into substance use, rather than at the transition from experimentation to regular use. The effect of parental monitoring on changes in adolescent substance use is mediated not so much by the nature of the adolescent's peer associates, but by its direct effect on the adolescent. Specifically, poorly monitored adolescents are more likely to use drugs, and drug-using adolescents seek out like-minded friends. Once an adolescent associates with drug-using peers, his or her own substance use approaches their level. CONCLUSIONS: Intervention effects should include both parents and community-level efforts. Parental monitoring is an effective tool both in the prevention of drug use and in the amelioration of drug use.

Adolescent↗
PubMed1993

Implications for trials in progress of publication of positive results.

It is not easy to decide, when results from similar trials appear, whether a trial still underway should be stopped or not. The weight of the other evidence has to be taken into account--as indeed it has to be for decisions by clinicians and by health service managers outside the settings of a trial. Taking the Systolic Hypertension in the Elderly Trial (SHEP) as an example, we show how its results are not unequivocal (ie, there is no proof beyond reasonable doubt). This verdict justifies the continuation of similar trials in progress. More generally--but again for individual clinicians and for trial organisers and again with SHEP as the example--we illustrate a bayesian approach to trial-termination decisions.

Aged↗
PubMed1993

WAY100135: a novel, selective antagonist at presynaptic and postsynaptic 5-HT1A receptors.

The novel phenylpiperazine derivative, (+/-)-WAY100135 (N-tert-butyl-3-(4-(2-methoxyphenyl)piperazin-1-yl)-2-phenylpro pionamide dihydrochloride), is a selective antagonist at both somatodendritic and postsynaptic 5-HT1A receptors. The IC50 of (+/-)-WAY100135 at the rat hippocampal 5-HT1A receptor was 34 nM, whereas its IC50 at a range of other receptor sites was > 2 microM. Up to a dose of 2.5 mg/kg i.v. (+/-)-WAY100135 induced a maximum 30% inhibition of raphe neuronal firing and (at 0.5 mg/kg i.v.) antagonised the inhibition of firing induced by 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) in anaesthetised rats. (+/-)-WAY100135 antagonised the action of 5-carboxamidoiodotryptamine in the guinea-pig ileum, with a pA2 of 7.2. (+/-)-WAY100135 had no agonist-like behavioural effects but antagonised the behavioural syndrome and hypothermia induced by 8-OH-DPAT in the rat and mouse, respectively. The interaction of (+/-)-WAY100135 with the 5-HT1A receptor was stereoselective; the (+)-enantiomer being markedly more active in binding, functional and behavioural studies. These data indicate that (+/-)-WAY100135 is the first highly selective antagonist at both somatodendritic and postsynaptic 5-HT1A receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

Venlafaxine exhibits pre-clinical antidepressant activity in the resident-intruder social interaction paradigm.

Venlafaxine, a novel 2-phenyl-2-(1-hydroxycycloalkyl) ethylamine, is a potent inhibitor of 5-hydroxytryptamine and noradrenaline reuptake and exhibits a profile of activity in pre-clinical in vitro biochemical studies predictive of antidepressant activity. The studies described here examined the effects of acute and chronic treatment with venlafaxine on the behaviour of resident rats confronted with an unfamiliar, non-treated, intruder conspecific. Ethological analysis of the social encounters revealed that acute, subcutaneous, treatment with venlafaxine, 20-180 mumol kg-1, induced a selective, dose-related, reduction in aggressive behaviour (ID50 = 24.87 mumol kg-1) concomitant with increased flight behaviour. In contrast, chronic treatment with venlafaxine, 20 mumol kg-1 day-1, via subcutaneously-implanted osmotic mini-pumps, induced a marked elevation in aggressive behaviour concomitant with reduced flight behaviour. These diametrically opposite effects of acute and chronic venlafaxine treatment on the agonistic behaviour of resident rats are consistent with the behavioural effects of similar treatment regimes previously identified for a range of antidepressant drugs that differ widely in their acute pharmacology. These data strongly support the potential antidepressant activity of venlafaxine and are consistent with the results of recent clinical trials which demonstrate that venlafaxine exhibits significant antidepressant activity.

Aggression↗
PubMed1993

Silent 5-HT1A receptor antagonists: utility as research tools and therapeutic agents.

The 5-hydroxytryptamine 5-HT1A receptor has been the focus of considerable research effort for over a decade. However, the definitive classification of this receptor and the full characterization of its pharmacology have awaited the development of highly selective 5-HT1A receptor antagonists. The only compounds available until recently have been either nonselective or partial 5-HT1A receptor agonists (or a combination of both). Confusion has arisen owing to the use of different pharmacological models in examining the functional activity of 5-HT1A receptor ligands. Several partial agonists display only antagonist activity in models of postsynaptic 5-HT1A receptor function, whereas their agonist properties are revealed in models of presynaptic, somatodendritic 5-HT1A autoreceptor function. In view of these considerations, the term 'silent antagonist' has been introduced to distinguish true 5-HT1A receptor antagonists from partial agonists. Allan Fletcher and colleagues review the pharmacological properties of the first selective silent 5-HT1A receptor antagonists that have been recently discovered and discuss the potential therapeutic utility of these novel compounds.

Animals↗
PubMed1993

A double-blind, placebo-controlled crossover trial of nadolol and verapamil in mild and moderately symptomatic hypertrophic cardiomyopathy.

OBJECTIVES: The aim of this study was to determine whether therapy with a beta-adrenergic or calcium channel blocking agent can improve the functional capacity and quality of life of patients with mild or moderately symptomatic hypertrophic cardiomyopathy. BACKGROUND: Both beta-blockers and calcium channel blockers may alleviate symptoms in hypertrophic cardiomyopathy, but previous studies have been performed in hospitalized patients or have been open studies without control subjects. METHODS: A randomized, double-blind crossover trial of nadolol, verapamil and placebo, administered for periods of 4 weeks each, was performed in 18 patients with mild or moderately symptomatic hypertrophic cardiomyopathy (10 men, 8 women; mean age +/- SD 39 +/- 17 years). A detailed symptom assessment, bicycle exercise testing, echocardiography and Holter monitoring were performed in each period. RESULTS: Two patients withdrew from the study owing to symptomatic sinus bradycardia during nadolol therapy. Neither drug improved maximal oxygen consumption (placebo 26 +/- 8, verapamil 23 +/- 6, nadolol 21 +/- 7 ml/kg per min; p = 0.1). Peak exercise work load was reduced by > or = 10 W in 13 patients (81%) during nadolol therapy and in 4 patients (25%) during verapamil therapy (p = 0.005, nadolol vs. verapamil). Despite the effects on exercise capacity, 13 patients (81%) preferred drug treatment (8 verapamil, 5 nadolol) over placebo (p = 0.001). Verapamil improved reported performance at work compared with nadolol (p = 0.01) and tended to improve other measures of health-related behavior and symptoms compared with nadolol and placebo. CONCLUSIONS: In patients with mild or moderately symptomatic hypertrophic cardiomyopathy, exercise capacity was not improved by nadolol or verapamil, and individuals were more often impaired by nadolol than with verapamil. Nevertheless, many patients derived symptomatic benefit from drug therapy, especially with verapamil.

Adolescent↗
PubMed1993

Combined infusions of morphine and ketamine for postoperative pain in elderly patients.

The value of using a combined infusion of morphine with a variable dose of ketamine for postoperative analgesia following upper abdominal surgery was assessed in a double-blind randomised study of 40 elderly patients. Four groups of 10 patients received an infusion of morphine at 1 mg.h-1, either alone, or combined with ketamine at a rate of 5, 10 or 20 mg.h-1. The addition of ketamine to a continuous infusion of morphine did not significantly improve either analgesia or postoperative lung function. Increasing the dose of ketamine resulted in an increased incidence of postoperative dreaming (p < 0.01).

Abdomen↗
PubMed1993

Further experience of public education for the early diagnosis of malignant melanoma in Leicestershire.

Publicity campaigns alerting the public to the need for early attention to malignant melanoma (MM) were conducted in Leicestershire, England during the summers of 1987, 1988 and 1989. There was a marked, and statistically significant, rise in the number of referrals with good prognosis MMs in the period immediately after the first campaign. In the 2 subsequent years, despite further publicity campaigns, the number of MMs diagnosed per week remained lower than the postpublicity peak of 1986/87. The postpublicity rise was less marked in 1987/88 and 1988/89. In the next year (1989/90), in which there was no publicity campaign, the total number of MMs seen was higher than in 1988/89. Numbers of MMs seen per week remained relatively steady throughout the year. There was again no publicity in 1990/91, and the total number of MMs diagnosed was about the same as in the previous year. There was a rise in the number of MMs seen per week in what would have been the postpublicity period of this year. The initial results would be consistent with the initial postpublicity rise in numbers of MMs seen being made up of lesions seen 'early', that is, in 1986/87 and 1987/88. Since these lesions were seen earlier than they would have been had there been no publicity, the number of MMs seen in 1988/89 was lower than it would otherwise have been and the publicity effort appeared to have less effect. By 1989/90 and 1990/91 this effect seems to have been wearing off. It may be that, at least in low MM incidence areas like the UK, it is better to pulse public education for the early diagnosis of melanoma rather than to use annual or continuous campaigns. However, longer-term experience, and the pooling of data between centres will be necessary to test this conclusion.

Age Factors↗
PubMed1993

Six monoclonal antibodies to the CD59 antigen.

CD59 defines an N-glycosylated glycoprotein expressed on various hemopoietic cells. It is anchored to the cell membrane by a glycosylpbospbatidylinositol linkage and restricts the action of homologous complement. Monoclonal antibodies 2/24, 182, Fib75.1, BRIC 229, MEM-43, and YTH 53.1 were compared by immunoblotting against normal erythrocyte ghosts. All six stained a diffuse band of 17-25 kDa, but BRIC 229 also detected bands at 35 and 80 kDa. 2/24 reacts with all red blood cells (RBCs) tested, including Rhnull; Ob; ii; Ko; FY:-1,-2,-3; JK:-1,-2,-3; S-s-U-; p; CO:-1,-2; Yt(a-); Jr(a-); Vel-; At(a-); Cr(a-); GE:-2,-3; Wr(a+b+ MkMk; Jo(a-); and Lan-. 2-aminoethylisotbiouronium bromide treatment of erythrocytes destroyed blotting and serologic reactivity of all six antibodies. Pronase treatment reduced serologic reactivity and blotting ability of all antibodies except BRlC 229. Reactivity of all six antibodies was reduced with RBCs from paroxysmal nocturnal hemoglobinuria patients. Flow cytometric analysis was used to demonstrate that 182, Fib75.1, BRIC 229, YTH 53.1, and MEM-43 competitively inhibited the binding of 2/24 to RBCs, thus demonstrating that all six antibodies detect epitopes on the same molecule.

Journal Article↗
PubMed1993

Nitrendipine in older patients with isolated systolic hypertension: second progress report on the SYST-EUR trial.

This report from the double-blind placebo-controlled SYST-EUR trial investigated whether modern antihypertensive drugs are suitable for maintaining long-term BP control in older (> or = 60 years of age) subjects with isolated systolic hypertension (SBP 160-219 mmHg and DBP < 95 mmHg). Active treatment consisted of nitredipine (10-40 mg/day) with the possible addition of enalapril (5-20 mg/day) and hydrochlorothiazide (12.5-25 mg/day), if necessary to reduce SBP to < 150 mmHg and by > or = 20 mmHg. Matching placebos were used in the control group. This analysis was restricted to 18 months of follow-up. The placebo (n = 456) and active treatment (n = 485) groups had similar characteristics at randomisation (sitting pressure 176/85 mmHg; age 73 years). SBP fell (P < 0.001) on average 10 mmHg more on active treatment than on placebo and DBP 4 mmHg more. Fewer patients remained on monotherapy in the placebo than in the active treatment group (P < 0.001); on placebo the second and third line medications were started earlier (P < 0.001). Nitrendipine tablets were discontinued in nine patients on placebo and in 29 patients assigned to active treatment (P < 0.001). In conclusion, a significant BP reduction can be achieved and maintained in older patients with isolated systolic hypertension treated with a calcium antagonist (associated with a converting-enzyme inhibitor and a thiazide, where necessary). Whether this BP reduction results in a clinically meaningful decrease of cardiovascular complications is under investigation.

Aged↗