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Biomedical subjects

F Forette

Publications and source records attributed to F Forette.

At least 19 recordsLinked to original sources
PubMed1992

[Prevention of pathological aging. The arterial hypertension example].

Studies conducted during the last decade have made it increasingly easier to distinguish between normal and pathological ageing. Previous studies on general populations had established a dogma: most of the major body functions, such as cardiac output, glomerular clearance, muscular strength, visual acuity and so forth, were supposed to decline with age. However, in recent studies on the effects of age on cardiac output all subjects with heart disease were excluded and as a result the negative correlation found between cardiac output and age disappeared, which shows that a phenomenon attributed to ageing was in fact caused by disease. This does not mean that there is no such thing as fundamental ageing, and indeed the mechanisms that maintain cardiac output are different in young and elderly subjects. These data are of more than theoretical interest, since it may be presumed that prevention, the instruments of which are already available in some fields, will modify the profile of ageing. The risk of arterial hypertension is not restricted to the classical cardiovascular diseases: it extends to other diseases, such as vascular dementia, which are potent factors of pathological ageing. Most of the controlled trials carried out in arterial hypertension have demonstrated that treating certain types of hypertension significantly reduces the morbidity and/or mortality of cardiovascular diseases. The specific properties of new antihypertensive drugs, such as angiotensin-converting enzyme inhibitors, open stimulating vistas on arterial ageing.

Adult↗
PubMed1992

Clinical trials in cognitive impairment in the elderly.

The pharmacological treatment of dementia is particularly difficult because of the uncertainty of the diagnosis and of the underlying pathogenetic processes, and because of the variable severity of the syndrome. This paper suggests several lines for future therapeutic trials in dementia. These include the need to work with homogenous populations and to take into account the natural history of the disease, the pharmacologic characteristics of the drugs, and the particular ethical considerations pertaining to demented patients. We review the diagnostic criteria for dementia, Alzheimer's disease (AD) and vascular dementia. We discuss the different types of therapeutic trial design, the problem of the duration of the protocol, the tools to evaluate the cognitive effects and the activities of daily living, and the use of a Clinical Global Impression of Change (CGIC). The results of some therapeutic trials in AD and vascular dementia are given as examples.

Activities of Daily Living↗
PubMed1992

Syst-Eur--a multicenter trial on the treatment of isolated systolic hypertension in the elderly: first interim report.

Syst-Eur is a multicenter placebo-controlled outcome trial designed by the European Working Party on High Blood Pressure in the Elderly to investigate the effect of antihypertensive treatment on the incidence of stroke in elderly patients with isolated systolic hypertension (ISH). Eligible patients must be at least 60 years old and have a systolic blood pressure averaging 160-219 mm Hg with a diastolic blood pressure less than 95 mm Hg. The present paper is an interim report on the first 316 patients randomized into this trial. The placebo (n = 170) and active treatment (n = 146) groups were similar at randomization with respect to age (73 +/- 8 years; mean +/- SD), sitting blood pressure (178 +/- 12 mm Hg systolic; 85 +/- 7 mm Hg diastolic), percentage of men (34%), and percentage of patients with cardiovascular complications (29%). After randomization blood pressure fell more (p less than 0.001) in patients on active treatment than in those in the placebo group (19 +/- 20 mm Hg systolic; 6 +/- 10 mm Hg diastolic vs. 7 +/- 19 and 1 +/- 10 mm Hg for sitting blood pressure). This first interim report on the Syst-Eur trial demonstrates that a multinational trial in elderly patients with ISH is feasible and that a significant blood pressure difference between the two treatment groups can be achieved and maintained. New centers are being recruited in order to randomize a total of 3,000 patients.

Aged↗
PubMed1992

Dermatoglyphic patterns in dementia of the Alzheimer type: a case-control study.

STUDY OBJECTIVE: The aim was to compare digital and palmar dermatoglyphics in subjects with dementia of Alzheimer type and in mentally healthy elderly controls. DESIGN: This design was a case-control study. SETTING: The study was carried out in geriatric units and retirement communities in the Paris area. PARTICIPANTS: Cases were women with clinically diagnosed Alzheimer type dementia according to DSM III-R criteria (n = 82), mainly with late onset of the disease. Controls were women aged 85 years or older without cognitive deterioration (n = 76). MEASUREMENTS AND MAIN RESULTS: Finger and palm prints obtained from both hands by the classical ink method were examined. Fingerprints were classified into four types of figures. On palms, palmar flexion creases, palmar axial triradii, true patterns of the hypothenar area, and main line terminations were described. Examinations were performed by two examiners blind to the subjects's diagnostic category. For the different patterns studied, no major differences between dementia patients and elderly controls were found. Nor was there evidence of high frequencies of features commonly observed in Down's syndrome (trisomy 21), which have previously, though sporadically, been reported. CONCLUSIONS: On one of the largest samples of Alzheimer dementia patients studied, and with evaluation blind to diagnosis, no evidence has been found that particular dermatoglyphic patterns occur like those observed in Down's syndrome, a disease which is related to dementia of the Alzheimer type.

Aged↗
PubMed1992

[SYST-EUR: a multicenter trial of treatment of systolic hypertension in aged subjects. An initial report].

Syst-Eur is a multicentre placebo-controlled outcome trial, designed by the European Working Party on High Blood Pressure in the Elderly (EWPHE), to investigate the effect of antihypertensive treatment on the incidence of stroke in elderly patients with isolated systolic hypertension (ISH). Eligible patients must be at least 60 years old and have a systolic blood pressure averaging 160-219 mmHg with a diastolic blood pressure less than 95 mmHg. The present paper in an interim report on the first 316 patients randomized into this trial. The placebo (N = 170) and active treatment (N = 146) groups were similar at randomization with respect to age (73 +/- 8 years; mean +/- standard deviation), sitting blood pressure (178 +/- 12/85 +/- 7 mmHg), percentage men (34%) and percentage of patients with cardiovascular complications (29%). After randomization blood pressure fell more (p < 0.001) on active treatment than in the placebo group (19 +/- 20/6 +/- 10 mmHg versus 7 +/- 19/1 +/- 10 mmHg for the sitting blood pressure). This first interim report on the Syst-Eur trial demonstrates that a multinational trial in elderly patients with ISH is feasible and that a significant blood pressure difference between the 2 treatment groups can be achieved and maintained. New centres are being recruited in order to randomize a total of 3,000 patients.

Aged↗
PubMed1991

Syst-Eur. A multicentre trial on the treatment of isolated systolic hypertension in the elderly: objectives, protocol, and organization.

The Syst-Eur Trial is a concerted action of the European Community's Medical and Health Research Programme. The trial is carried out in consultation with the World Health Organization, the International Society of Hypertension, the European Society of Hypertension and the World Hypertension League. This article describes the objectives and the protocol of Syst-Eur, a multicentre trial designed by the European Working Party on High Blood Pressure in the Elderly (EWPHE), to test the hypothesis that antihypertensive treatment of elderly patients with isolated systolic hypertension results in a significant change in stroke morbidity and mortality. Secondary endpoints include cardiovascular events, such as myocardial infarction and congestive heart failure. To be eligible patients must be at least 60 years old and have a systolic blood pressure averaging 160-219 mmHg with a diastolic pressure less than 95 mmHg. Patients must give their informed consent and be free of major cardiovascular and non-cardiovascular diseases at entry. The patients are randomized to active treatment or placebo. Active treatment consists of nitrendipine (10-40 mg/day), combined with enalapril (5-20 mg/day) and hydrochlorothiazide (12.5-25 mg/day), as necessary. The patients of the control group receive matching placebos. The drugs (or matching placebos) are stepwise titrated and combined in order to reduce systolic blood pressure by 20 mmHg at least to a level below 150 mmHg. Morbidity and mortality are monitored to enable an intention-to-treat and per-protocol comparison of the outcome in the 2 treatment groups. A one-year pilot trial (1989) showed that the protocol is practicable. The Ethics Committee therefore decided to start the definite study (1990), in which randomized patients will be followed for 5 years. Recruitment of new centres and of the required 3,000 patients will last 3 years (until 1993).

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PubMed1991

Is prevention of vascular dementia possible? The Syst-Eur Vascular Dementia Project.

Vascular dementia (VD) is the second most common cause of dementia in the elderly after Alzheimer's disease (AD). Prevalence estimates from community surveys indicate that, on average, 5% of persons over 65 and 15 to 20% of people over 80 suffer from "severe dementia". Clinico-pathological studies have shown that AD accounts for 50 to 60% of the cases and VD for about 10 to 20%; 20% of the patients have both disorders. The incidence rate of VD ranges from 7 per 1,000 person-years in normal volunteers to 16 per 1,000 person-years in subjects with risk factors for strokes, particularly high blood pressure. The only effective therapeutic approach to VD is the prevention of strokes, mainly through the treatment of hypertension; however, none of the therapeutic trials has included VD prevention as one of its treatment goals. Syst-Eur Study is a European placebo controlled trial which aims to determine whether morbidity and mortality are changed when elderly patients (60 years and over) with isolated systolic hypertension are treated. In this trial, the incidence of VD will be carefully recorded during the five year follow-up of the expected 3,000 patients. The present side project to the Syst-Eur trial will specifically address the following questions: does antihypertensive treatment reduce the incidence of VD?, and how do the cognitive functions of elderly patients change when treated with active or placebo treatment? The protocol is based on the administration of the MMS (Folstein) once a year to all patients. If the MMS score is 23 or less, a set of criteria will be used to establish the diagnosis of vascular dementia. A pilot study has demonstrated the feasibility of the trial. The main study is in progress.

Aged↗
PubMed1991

Hypertension and the risk of dementia in the elderly.

Vascular dementia is the second most common type of dementia in the elderly after the dementia of Alzheimer's disease. Six forms of vascular dementia have been described: multi-infarct dementia, lacunar dementia, Binswanger's subcortical encephalopathy, cerebral amyloid angiopathy, white-matter lesions associated with dementias, and single-infarct dementia. Each is described. Severe dementia is found in 5% of persons over age 65 and in 15% to 20% of persons over age 80 years. Alzheimer's disease accounts for 50% to 60% of cases of severe dementia and vascular dementia for 10% to 20%; 20% of the patients have both disorders. The incidence of vascular dementia, which seems to be declining, is about 7/1,000 persons/year. Hypertension is the most powerful risk factor for all vascular dementias. Vascular dementias can be accurately diagnosed by using clinical and mental state examinations, Diagnostic and Statistical Manual of Mental Disorders criteria, ischemic scores, and computed tomography or magnetic resonance imaging. The most successful treatment of vascular dementia is the prevention of cerebral infarcts. Study of the incidence of vascular dementias and their treatment will be included in the European Trial on Systolic Hypertension in the Elderly (SYST-EUR) of 3,000 elderly hypertensive patients.

Aged↗
PubMed1991

The influence of age on renal prostaglandin synthesis in man.

The purpose of our study was to determine influence of age on renal prostaglandin (PG) synthesis in man. Urinary prostaglandins 6-Keto-PGF1 alpha, TxB2, PGE2 and PGF2 alpha were measured in 45 normotensive subjects aged from 20-95 years. Urinary 6-Keto-PGF1 alpha excretion, reflecting mainly renal cortical prostacyclin synthesis, decreased significantly with age, while urinary TxB2 showed the opposite development. The ratio of urinary 6-Keto-PGF1 alpha/TxB2 decreased with age. PGE2 excretion was preserved in old subjects probably because the age-dependent decrease in renal function concerns mainly the cortex and spares the medulla. PGF2 alpha synthesis was least influenced by age. This age-dependent decrease in renal prostacyclin synthesis may play a role in the renal alterations of the elderly.

Adult↗
PubMed1990

Age-related effects of placebo and active treatment in patients beyond the age of 60 years: the need for a proper control group.

The age-related response to placebo and active antihypertensive treatment was evaluated in 742 elderly hypertensive patients who were followed in the double-blind placebo-controlled trial conducted by the European Working Party on High blood pressure in the Elderly (EWPHE). In the two treatment groups, the fall in systolic and diastolic blood pressures after 3 months was negatively correlated with age (P less than 0.02), indicating that the hypotensive effect of placebo and active treatment was more pronounced in older patients. Further comparison of the two treatment groups failed to demonstrate any statistical differences in the slopes of the hypotensive effect on age. These conclusions were not altered by cumulative adjustments for baseline blood pressure, pulse rate, serum creatinine and the presence of cardiovascular complications at entry. In conclusion, in the present study, a similar blood-pressure-lowering action which increased with age was observed on active and placebo treatment; thus, proof that an observed age-related hypotensive effect is caused by a particular drug requires comparison with a control group on placebo.

Aged↗
PubMed1990

[Value and limits of medical treatment of hypertension in the aged person].

Most of the therapeutic trials (VA Study, HDFP, Australian Therapeutic Trial, EWPHE Study, Coope's Study) are in favour of the benefit of antihypertensive treatment over the age of sixty. But, on the other hand, information is lacking on:--The effectiveness of treatment of isolated systolic hypertension;--The effectiveness of treatment in very old people, particularly over eighty;--The effectiveness of treatment in preventing conditions which were not included in the former trials such as vascular dementias. Two trials concerning elderly patients with systolic hypertension are in progress, the SHEP Study in the USA and the European study called Syst-Eur. It is expected that these trials will give answers allowing a more accurate management of this major risk factor for cardiovascular diseases in the Elderly.

Aged↗
PubMed1989

Relation between mortality and treated blood pressure in elderly patients with hypertension: report of the European Working Party on High Blood Pressure in the Elderly.

OBJECTIVE: To investigate the relation between mortality and treated systolic and diastolic blood pressures. DESIGN: Randomised double blind placebo controlled trial. Mortality in the two treatment groups was examined in thirds of treated systolic and diastolic blood pressures. PATIENTS: 339 And 352 patients allocated to placebo and active treatment, respectively. The groups were similar at randomisation in sex ratio (70% women), mean age (71.5 years), blood pressure (182/101 mm Hg), and proportion of patients with cardiovascular complications (35%). MEASUREMENTS AND MAIN RESULTS: In the placebo group total mortality rose with increasing systolic pressure whereas it had a U shaped relation with diastolic pressure, the total lowest mortality being in patients in the middle third of the distribution of diastolic pressure. In the group given active treatment total mortality showed a U shaped relation with systolic pressure and an inverse association with treated diastolic pressure. In both groups cardiovascular and non-cardiovascular mortality followed the same trends as total mortality. The increased mortality in the lowest thirds of pressure was not associated with an increased proportion of patients with cardiovascular complications at randomisation or with a fall in diastolic pressure exceeding the median fall in pressure in each group. In contrast, patients in the lowest thirds of pressure showed greater decreases in body weight and haemoglobin concentration than those in the middle and upper thirds of pressure. CONCLUSIONS: In patients taking active treatment total mortality was increased in the lowest thirds of treated systolic and diastolic blood pressures. This increased mortality is not necessarily explained by an exaggerated reduction in pressure induced by drugs as for diastolic pressure a U shaped relation also existed during treatment with placebo. In addition, patients in the lowest thirds of systolic and diastolic pressures were characterised by decreases in body weight and haemoglobin concentration, and the patients in the lowest thirds of diastolic pressure taking active treatment also by an increased non-cardiovascular mortality, suggesting some deterioration of general health.

Aged↗
PubMed1989

Reliability of clinical criteria for the diagnosis of dementia. A longitudinal multicenter study.

The reliability of the clinical diagnosis of dementia was estimated by comparing the diagnosis made at 1-year intervals on 55 consecutive subjects with suspected cognitive impairment seen at three different centers by neurologists and gerontologists. The diagnosis was based on history and clinical examination, the criteria of the Diagnostic and Statistical Manual of Mental Disorders (revised ed 3), the Modified Ischemic Score, and a computed tomographic scan. Fifty-two of 55 subjects were given the same diagnosis a year later indicating a reliability of 95%. The study shows that a diagnosis of dementia established by simple clinical criteria comparable to the NINCDS/ADRDA criteria affords sufficient reliability to allow the comparability of groups at different centers for purposes of research, including research on the evaluation of the efficacy of pharmacologic treatment.

Aged↗
PubMed1989

Nicardipine in elderly patients with hypertension: a review of experience in France.

A double-blind, placebo-controlled clinical trial in France has studied the efficacy and safety of nicardipine in 31 elderly patients, aged 57 to 95 years (mean age 84 years), 16 of whom were actively treated with nicardipine, 10 to 30 mg three times a day (mean dose 69.4 mg/day). After 4 weeks, nicardipine lowered mean blood pressure (186/99 to 150/83 mm Hg; p less than 0.001), and the changes in systolic and diastolic blood pressure were significantly greater in the nicardipine group than in the placebo group. Nicardipine was well tolerated; orthostatic hypotension was not observed and there was no change in heart rate. Plasma renin activity (PRA) was measured in eight patients, but there was no correlation between PRA and the antihypertensive effect of nicardipine. Results of a pharmacokinetic study performed in 15 elderly patients showed a rapid rate of absorption and higher plasma levels than those observed in younger patients with hypertension (mean age 54 years). The results support those of the major French multicenter open study of 29, 104 elderly patients with hypertension (mean age 64 +/- 12 years) treated with nicardipine. The findings of this trial are reviewed and discussed, and recommendations made on the directions for future research in cardiovascular medicine with calcium channel blockers. Results of the trials discussed in this article show that nicardipine is an effective and well-tolerated drug in elderly patients and has wide-ranging effects on the cardiovascular system.

Aged↗
PubMed1989

Alzheimer's disease and THA: a review of the cholinergic theory and of preliminary results.

The cholinergic theory is based on the assumption that acetylcholine (ACh) metabolism plays an important role in memory processes and that the deterioration of memory and other cognitive functions in Alzheimer's disease (AD) is directly related to degeneration of cerebral presynaptic cholinergic neurons. This article reviews various therapeutic strategies based on this theory and particularly that of using cholinesterase inhibitors such as tetrahydroaminoacridine (THA). The few available studies--all preliminary--on THA are reviewed. They show that THA is neither a cure nor a definitive treatment for AD. However, the preliminary reports suggest for the most part a certain degree of efficacy, greater at any rate than the efficacy of other pharmaceutical agents tried so far. Despite the apparent multiplicity of pharmacological actions of THA, it appears that the cholinergic hypothesis remains valid and should be pursued further.

Aging↗
PubMed1989

[Significance of inhibitors of conversion enzymes in elderly subjects. The example of perindopril].

The effectiveness and safety of perindopril in elderly hypertensive patients has clearly been demonstrated. In a randomized, double-blind drug versus placebo study involving 34 such patients of mean age 84 years, we observed a 10 p. 100 fall in systolic arterial pressure (p less than 0.01) and a 9 p. 100 fall in diastolic arterial pressure (p less than 0.01) in the perindopril group. The corresponding figures in the placebo group were 5 p. 100 and 4 p. 100 respectively, the difference between the two groups not being significant. The drug was well tolerated, both clinically and biochemically. However, a significant (p less than 0.01) increase in blood potassium level (albeit within normal limits) was observed in the treated group. An open trial conducted in 91 patients (mean age 79.1 years) followed up for 6 years confirmed the acceptability of the drug despite a transient decrease of creatinine clearance recorded in one patient. The effectiveness of perindopril, evaluated less unquestionably in this open trial, was excellent, the hypertension being controlled at the end of treatment in 92.5 p. 100 of the patients. In a trial performed on healthy volunteers, Reid found that perindopril had a greater effect of arterial pressure in elderly subjects, probably due in part to their high blood pressure and to an earlier and more prolonged inhibition of the angiotensin-converting enzyme (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗