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Biomedical subjects

A E Fletcher

Publications and source records attributed to A E Fletcher.

At least 55 records · Page 3Linked to original sources
PubMed1996

Use of surrogate respondents in studies of stroke and dementia.

A study was performed to determine the misclassification of information on exposure when surrogate informants are interviewed. Information from nondementia patients admitted to a geriatric ward was compared with that obtained from the patients' family members or friends (informants). Thirty-seven patients were recruited (17 with current or previous stroke, and 20 no history of stroke). Information on past medical and family history, cigarette smoking and alcohol consumption was collected using a questionnaire that was administered independently to patients and informants. For nonstroke patients, agreement on smoking and alcohol consumption at different ages was generally good. Informants reported slightly lower smoking and alcohol intake than patients: 1.3 fewer total pack-years (95% CI, -3.8, +6.5) and 2.7 fewer units/week (95% CI, -1.5, +6.9), respectively. For stroke patients, informants tended to report a greater smoking consumption at all ages, and a slightly higher alcohol consumption. Informants reported an excess of 7.4 total pack-years (95% CI, -1.2, + 16.0) and 2.19 units/week (95% CI, -1.0, +5.3). Agreement for medical history was good, except for hypertension. There was poor agreement for family medical history. The impact of misclassification is discussed.

Aged↗
PubMed1996

Nutritional supplementation in elderly medical in-patients: a double-blind placebo-controlled trial.

The aim of this study was to assess the effect of vitamin and/or glucose energy supplementation in elderly medical patients on an intention-to-treat basis. One hundred and six elderly medical in-patients were entered into a double-bind placebo-controlled factorial trial of glucose energy and vitamin supplementation. Supplementation was given for 1 month. This trial was designed to detect a > 2 kg increase in weight and > 3 g/l increase in serum albumin between active and placebo supplementation in 100 patients with 90% power (p < 0.05). Other outcome measures included changes in Barthel activities of daily living, length of stay, and mental test score (MTS). No interaction between vitamin and glucose supplementation was demonstrated. Active energy supplementation with glucose alone was associated with a +0.6 kg change in weight and +0.7 g/l change in albumin [95% confidence interval (CI) -0.8, +2.0 and -1.3, +2.8, respectively]. The respective changes for active vitamin supplementation were -0.6 kg for weight and +0.5 g/l for albumin (95% CI -2.1, +0.8 and -1.5, +2.6, respectively). There were no significant differences in mental test score, Barthel score, or length of stay between the two groups. Compliance with the glucose energy supplementation was poor with only one-third of patients consuming more than 50% of the offered drink. We conclude that the giving of glucose alone and/or vitamin supplementation in elderly patient is of no benefit on an intention-to-treat basis.

Aged↗
PubMed1995

Prolonging life in elderly people: a worthwhile goal of medical care.

The very elderly (over 80 years) have a relatively high level of disability and dependency, and this has been reported to be a greater problem in women. It has, therefore, been proposed that there may be little to gain from prolonging life of the very elderly, especially very elderly women. However, there is very little evidence to suggest that increasing survival leads to a higher prevalence of disability at a given age. Preventive measures that prolong life appear to postpone both morbidity and mortality. Moreover, there is little reliable evidence that an elderly woman is more dependent than a man of the same age. It is also suggested that there is a 'cap' on survival and, therefore, we should concentrate on preventing morbidity and compress it into the last few years of life. We consider whether or not the elderly are approaching a 'cap' on survival and think that they are not. We conclude that preventive medicine in the elderly should aim to prolong survival and prevent morbidity. It is uncertain whether morbidity can be prevented more than mortality or vice versa. The concept of compressing morbidity at the end of life is an attractive concept, but data are lacking to support this idea.

Aged↗
PubMed1995

Alcohol intake and cardiovascular mortality in hypertensive patients: report from the Department of Health Hypertension Care Computing Project.

OBJECTIVE: To determine the benefits and risks of drinking alcohol in treated hypertensives. DESIGN: A prospective study of 6,369 hypertensives (3,161 men) attending primarily hospital clinics in the UK. METHODS: Relative risks both for drinkers compared with non-drinkers and for level of alcohol consumption were calculated for mortality from ischaemic heart disease, stroke, non-circulatory and all causes. RESULTS: At presentation 76% of the men and 48% of the women reported recent alcohol consumption. Compared with drinkers, non-drinkers were older, less likely to smoke and had a higher untreated blood pressure. After adjustment for confounding factors, male drinkers had a reduced risk of stroke mortality and possibly of ischaemic heart disease mortality. Similar results were observed in women for stroke mortality but not for ischaemic heart disease mortality. The trend remained after adjustment for previous cardiovascular disease. In men the lowest risk of ischaemic heart disease mortality occurred at intakes of > 21 units per week and stroke mortality was lowest at 1-10 units per week. Men consuming > 21 units per week had a twofold higher non-circulatory mortality. Total mortality was lowest in men who drank 1-10 units per week. Similar effects of alcohol on cardiovascular mortality were observed in women. CONCLUSIONS: Alcohol intake may reduce stroke mortality in treated hypertensives. Ischaemic heart disease mortality in men may also be reduced, especially at higher intakes ( > 21 units per week). The beneficial effects were offset by increasing incidence of non-circulatory causes of death. Alcohol consumption of 1-10 units per week was associated with the lowest mortality in men.

Adolescent↗
PubMed1995

Proportion of patients with isolated systolic hypertension who have burned-out diastolic hypertension.

In a community survey of 3242 subjects, 1663 did not initially have isolated systolic hypertension (ISH) and were re-screened an average of 8 years later. ISH developed in 53 (22%) of untreated patients with previous diastolic hypertension. Similarly, 8% of subjects with transient hypertension and 8% of normotensive controls developed ISH. Of all cases of ISH, 16% had previous diastolic hypertension. These subjects were more likely to have continued to smoke (P = 0.01) and lost more weight (P = 0.001) than patients with ISH who did not have burned-out diastolic hypertension.

Adolescent↗
PubMed1994

The assessment of biological age: a report from the Department of Environment Study.

Indicators of ageing were measured in 397 male and 130 female London Civil Servants aged from 37 to 58 years of age. Grey hair, skin inelasticity, and arcus senilis were strongly and independently related to chronological age. Also independently related were serum albumin (negatively related in both sexes), baldness, serum creatinine, systolic blood pressure, serum calcium (negatively) and ESR in men, and serum cholesterol in women. Chronological age was regressed on the above variables for men and women separately to provide regression equations. Biological age for an individual was calculated by entering his or her results and calculating the residuals. Biological age in those who stopped smoking tended to be younger than chronological age by an average of 12-13 months in men and 1-4 months in women. Men and women who had never smoked had higher biological than actual ages but not after adjusting for regression dilution bias. Men who currently smoked had higher biological ages of 2-3 months but not women smokers (4-6 months lower). Similarly, men of lower employment grades had an average biological age 13 months older and women 8 months, compared with higher employment grades. These differences between employment grade appeared to be due to ESR, arcus senilis, systolic blood pressure and serum cholesterol. These four measurements may be markers of biological rather than chronological age, and the value of attempting to measure biological age is discussed.

Adult↗
PubMed1994

Age differences in biochemical and hematological measures during middle age.

Biochemical and hematological measures possibly associated with ageing were measured on a single occasion in 3402 male and 2152 female London Civil Servants aged from 35 to 59 years of age. These included erythrocyte sedimentation rate (ESR), blood hemoglobin and serum albumin, calcium, bilirubin, creatinine, urea, urate, high density lipoprotein (HDL), and total cholesterol. Independently and positively related to age were ESR with an estimated 47% 'increase' in men over the 15 years between ages 40 to 55 and a 40% increase in women; serum urea had a 6%/15-year increase in men and 20% in women; total cholesterol had a 6%/15-year increase in men and 18% in women; serum creatinine 'increased' by 2%/15-years in men and 5% in women. In women, urate, HDL cholesterol and hemoglobin increased with age group. Negatively related to age was serum bilirubin in both sexes (8% and 6% 'fall'/15-years in men and women respectively). Serum albumin and calcium fell with age group in men. The sexes differed in their relationship to aging for total cholesterol and HDL cholesterol (greater increase in women), serum calcium (small decrease in men and small increase in women), urate and hemoglobin (increases in women but not men). Urea increased more in women than men, and albumin decreased more in men than women (p < 0.001 for all comparisons with the exception of HDL cholesterol, p < 0.01). Changes during the menopause were thought to explain some of these findings.

Adult↗
PubMed1994

A comparison of three quality of life instruments in subjects with angina pectoris: the Sickness Impact Profile, the Nottingham Health Profile, and the Quality of Well Being Scale.

Three instruments for the assessment of quality of life, the Quality of Well Being index (QWB), the Nottingham Health Profile (NHP) and the Sickness Impact Profile (SIP) were assessed in 59 patients with angina pectoris. The NHP showed increased statistically significant impairment with higher New York Heart Association (NYHA) class in 4 out of 6 subscales but not in single responses to questions on daily life. In the SIP 9 out of 11 dimensions increased with NYHA grade as did the physical and psychosocial subscores and the total score. There were statistically significant increases in six of the eleven dimensions. In the QWB an increase was observed only for two out of four categories employed in this instrument. The QWB was the most difficult to administer and thought likely to be insensitive to changes in anginal pain. There was a high level of agreement in similar dimensions of NHP and SIP. A psychological distress score was evaluated using the Symptom Rating Test and correlated with all summary dimensions of both instruments. The coefficients of variation were lower in SIP than in NHP categories. In conclusion quality of life instruments like NHP and SIP may be able to identify treatment effects in angina patients and so yield a useful addition to the traditional measures employed for the assessment of their condition.

Adult↗
PubMed1994

The effect of low dose lofepramine in depressed elderly patients in general medical wards.

A double-blind randomised controlled trial of the effect of low dose lofepramine (70 mg once daily) against placebo was carried out on depressed elderly inpatients on general medical wards for the elderly, comparing measures of depression and side-effects between the randomised groups. Patients were identified for the study using the Geriatric Depression Scale (GDS) and the Brief Assessment Schedule Depression Cards (BASDEC). Sixty-three subjects were randomised: 46 patients completed the entire trial of 28 days treatment. BASDEC and GDS were administered on day 8 post-admission, and depressed patients were randomised double-blind to either low dose lofepramine (70 mg daily) (n = 23) or placebo (n = 23). Assessment of changes in depressive states were made using the Montgomery Asberg Depression Rating Scale (MADRS) on days 8, 18 and 36 post-admission. Both groups improved by a similar amount during the trial. Lofepramine tended to be more effective than placebo in those patients who were more depressed (GDS > or = 18). On the other hand, subjects who were less depressed (i.e. GDS < 18) improved more on placebo than lofepramine. Low dose lofepramine may prove useful in moderately or severely depressed patients treated for only 4 weeks. However, low dose lofepramine is not indicated for mild (GDS 15-18) depression.

Administration, Oral↗
PubMed1994

Optimal blood pressure control in treated hypertensive patients. Report from the Department of Health Hypertension Care Computing Project (DHCCP).

BACKGROUND: We wished to determine the range of treated systolic (SBP) and diastolic blood pressure (DBP) associated with the best survival in hypertensive patients. METHODS AND RESULTS: We conducted a cohort study of patients enrolled in the DoH Hypertension Care Computer Project. Five specialist hypertension clinics (95% of patients) and general practitioners (5%) followed 6214 patients (3070 men and 3144 women) with an average age of 52 years for a mean of 107 months. Total, cardiovascular, ischemic heart disease, (IHD) and stroke mortality were the outcome measures. Age-adjusted relative hazard rates were calculated giving the effect on mortality of systolic or diastolic pressure being higher by 1 mm Hg. In men the optimal level of SBP for all four measures of mortality was the lowest pressure range observed, 92 to 133 mm Hg (median 127). For women the treated SBP range of 96 to 148 mm Hg (median 137) was associated with a low total mortality and also with low to moderate rates for IHD and stroke mortality. Relative hazard rates (P < .001) for IHD mortality were 1.010 for men and 1.013 for women and for stroke mortality were 1.018 and 1.021, respectively. The results were similar in men under and over the age of 60. SBP and DBP tended to be more important in younger than older women. For treated DBP in men, a pressure of 55 to 94 mm Hg (median 87) was associated with a low total mortality. The lowest stroke mortality in men was observed for a DBP range of 55 to 83 mm Hg (median 80) but with a tendency for an increase in IHD mortality. For women DBP < 95 mm Hg (range 55 to 94, median 87) also was associated with a low total mortality. IHD mortality in women was not closely related to treated DBP, relative hazard rate = 1.003, [95% confidence index (CI); 0.990,1.017] but the relative hazard rate for men was 1.011, (95% CI; 1.000, 1.022). The relative hazard rates for treated DBP and stroke were high at 1.035 and 1.028 for men and women, respectively (P < .001). IHD mortality increased in the one third of patients with the greatest fall in DBP on treatment, provided they were not initially in the one-third group with highest untreated DBP. CONCLUSIONS: The best overall survival was associated with a treated SBP of < 134 mm Hg in men and < 149 mm Hg in women and a treated DBP of < 95 mm Hg.

Adult↗
PubMed1994

The Hypertension in the Very Elderly Trial (HYVET). Rationale, methodology and comparison with previous trials.

The Hypertension in the Very Elderly Trial (HYVET) is a multicentre, open, randomised, controlled trial. The aim of this trial is to investigate the effect of active treatment on stroke incidence in hypertensive patients over the age of 80 years. Secondary end-points include total cardiovascular mortality and morbidity. Entry criteria include a sustained sitting systolic blood pressure of 160 to 219mm Hg plus a sustained sitting diastolic pressure of 95 to 109mm Hg. Also required is a standing systolic blood pressure of at least 140mm Hg. Patients must give their informed consent, and be free of congestive heart failure requiring treatment, gout, renal failure or a recent cerebral haemorrhage. Patients are to be randomised to 3 groups-(i) no treatment; (ii) treatment with a diuretic [bendroflumethiazide (bendrofluazide)]; or (iii) treatment with an angiotensin converting enzyme (ACE) inhibitor (lisinopril). Starting dosage for bendroflumethiazide and lisinopril is 2.5 mg/day. In order to achieve goal sitting systolic and diastolic blood pressures (< 150/80 mm Hg), a doubling of the dosage is allowed. Furthermore, slow release diltiazem (120 mg/day increasing to 240 mg/day if required) may be added to the medication of the actively treated groups. These drugs have been chosen as inexpensive and appropriate representatives of their therapeutic classes. 700 patients in each group (a total of 2100) will be sufficient to detect a 40% difference in cerebrovascular events between no treatment and active treatment (alpha = 0.01, 1-beta = 0.90). These numbers will also detect a difference in total mortality of 25% and in cardiovascular mortality of 35%. The pilot phase of the trial has been started with support from the British Heart Foundation. Centres which are interested in taking part should contact C.J. Bulpitt or any of the other authors.

Aged↗
PubMed1994

Prognostic significance of blood pressure in the very old. Implications for the treatment decision.

A positive relationship between blood pressure and mortality at the age of 60 to 69 years becomes a negative relationship in men over the age of 75 years and in women over the age of 85 years, with hypertensive individuals living longer. This negative relationship in very old people probably reflects cardiac, respiratory and neoplastic disease in those with low blood pressure, and good myocardial function in those with high blood pressure. Therefore, in very elderly hypertensive people we cannot conclude that a reduction in blood pressure will not be beneficial, e.g. in reducing stroke events. However, the results of clinical trials of antihypertensive treatment in the elderly provide inadequate evidence to assess the benefit of treating hypertensive individuals over the age of 80 years. Randomly allocated controlled trials are required in this age group. The antihypertensive treatments that may be most suitable for the very elderly are diuretics with a beta-adrenergic blocking drug added if necessary. Angiotensin converting enzyme (ACE) inhibitors and calcium channel blockers have not, as yet, a proven role in the treatment of hypertension in the very old.

Aged↗
PubMed1994

Quality-of-life instruments in hypertension.

This review considers the choice of dimensions to be assessed and the practical problems of measuring quality of life in hypertensive patients. The dimensions of symptomatic well-being, psychological well-being, sleep, sexual function and cognitive function should be assessed. Symptomatic well-being may be measured by many different instruments, and that devised by the authors has been used extensively. The results in different trials may therefore be examined for consistency and sensitivity. Psychological well-being has been assessed by the Psychological General Well-Being Index, the Symptom Rating Test and the Profile of Mood States. The response of these instruments is discussed. The assessment of sleep, sexual function and cognitive function is also described. It is recommended that quality-of-life instruments to be employed in trials of antihypertensive drugs are known to be sensitive to the effects of such drugs.

Attitude to Health↗
PubMed1994

Psycho-emotional stress and salt intake may interact to raise blood pressure.

AIM: This study examined whether work-related aspects of stress, alone or in association with a high salt intake, are associated with a raised blood pressure. METHODS: A total of 384 male civil servants (35-51 years) collected a 24h urine sample and were interviewed using measures of work-related stress. Their blood pressure was taken at a civil-service medical clinic and was self-measured at home. RESULTS: Systolic/diastolic pressure averaged ( +/- SD ) 135 +/- 19/84 +/- 14 mmHg at the clinic and 123 +/- 16/80 +/- 11 mmHG on self-measurements at home. The 24h urinary sodium excretion was 172 +/- 65 mmol. The overall stress score was categorized as low in 98 men, medium in 193 men and high in 93 men. Stress itself was not associated with an elevated pressure. However, in multivariate analyses with adjustments for age and body mass index, a stress-sodium interaction in the determination of the clinic systolic (P = 0.05) and diastolic (P = 0.08) pressure became apparent. At a sodium excretion of 100 mmol/24h (10th percentile), increasing stress from low to high was associated with a fall in pressure, averaging 4.5 mmHg for systolic pressure and 1.4 mmHg for diastolic pressure. By contrast, at 250 mmol/24h (90th percentile) the same stress increase was associated with a rise in pressure of 6.3 mmHg systolic and 5.9 mmHg diastolic. CONCLUSION: The present study suggests that sodium intake and work-related stress may interact to determine blood pressure. This interaction is probably dynamic in nature, so that the contribution of each factor to blood pressure can only be determined if both are measured.

Adult↗
PubMed1994

Cough with angiotensin converting enzyme inhibitors: how much of a problem?

PURPOSE: To review the occurrence of angiotensin converting enzyme (ACE) inhibitor-related cough, and to examine its impact on the quality of life. DATA SOURCES: Data from published reports, postmarketing surveillance studies, hospital case series and randomly allocated controlled trials were reviewed. Data are presented from a nested case-control study examining the effects of ACE inhibitor-related cough in 36 subjects compared with 69 controls on various measures of quality of life. RESULTS: Low rates of ACE inhibitor-related cough were found in postmarketing studies, ranging from 0.1% (early studies) to 3%. Much higher figures were reported from double-blind randomly allocated controlled trials using self-administered questionnaires; the net increase over baseline was between 13 and 25% compared to 2% with the comparator drug. The nested case-control study suggested that the ACE inhibitor-related cough is associated with some deterioration in well-being. During ACE inhibitor treatment the patients tended to be more fatigued (P = 0.1) and depressed (P < 0.05) than controls. Reports of a sore throat increased by 27% (P < 0.01). CONCLUSIONS: Cough is a common side effect of ACE inhibitor treatment, with conservative estimates suggesting that around one in 10 patients treated with an ACE inhibitor will develop a dry persistent cough. Half of these may be withdrawn from treatment. This cough is probably associated with some deterioration in well-being, but larger studies are required to confirm this.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Biological properties of the benzodiazepine amidine derivative L-740,093, a cholecystokinin-B/gastrin receptor antagonist with high affinity in vitro and high potency in vivo.

A novel series of 5-amino-1,4-benzodiazepin-2-one derivatives (amidines), which contain a cationic solubilizing group and which are antagonists for the cholecystokinin (CCK)-B receptor, have been identified. Optimization of this series led to the identification of an azabicyclononane amidine, L-740,093 [N-[(3R)-5-(3-azabicyclo[3.2.2]nonan-3-yl)-2,3-dihydro-1-methyl-2- oxo- 1H-1,4-benzodiazepin-3-yl]-N'-(3-methylphenyl)urea], that bound with high affinity of CCK-B receptors from guinea pig cerebral cortex (IC50 of 0.1 nM) and had a CCK-B/CCK-A receptor selectivity of 16,000. In comparison, L-365,260 had 85-fold lower affinity (8.5 nM) and was only 87-fold selective for CCK-B over CCK-A receptors. L-740,093 bound with high affinity to guinea pig gastrin receptors in vitro (IC50 of 0.04 nM). Electrophysiological studies on slices of rat ventromedial hypothalamic nucleus showed that L-740,093 produced rightward shifts of the concentration-response curve for the CCK-B receptor agonist pentagastrin (Kb of 0.06 nM). L-740,093 blocked pentagastrin-induced gastric acid secretion in anesthetized rats with a 50% inhibitory dose of 0.01 mg/kg, intraperitoneally, showing 100-fold greater activity, compared with L-365,260 (50% inhibitory dose of 1 mg/kg, intraperitoneally). An ex vivo binding assay in mice was used to investigate the interaction of L-740,093 with central CCK binding sites. After intravenous administration, L-740,093 inhibited ex vivo binding dose dependently, with a 50% effective dose of 0.2 mg/kg. These studies demonstrate that L-740,093 is the most potent and selective CCK-B antagonist yet described and that it has excellent central nervous system penetration.

Animals↗