Biomedical subjects

F Delahaye

Publications and source records attributed to F Delahaye.

At least 91 records · Page 5Linked to original sources

PubMed1992

Cardiomyoplasty does not preclude heart transplantation.

Stimulated skeletal muscle grafts have been proposed to improve left ventricle function in patients with severe myocardial failure. In 1 particular case reported here, however, the postoperative functional improvement was only transient and disabling heart failure recurred after 9 months in spite of a vigorous latissimus muscle contraction. Heart transplantation was proposed to this patient and performed successfully. Technically, the key to heart removal depends on the retrograde dissection of the ventricular cavities, starting from the right atrioventricular groove. The intraoperative observations confirmed the viability of the latissimus dorsi muscle, inefficient on a highly dilated cardiomyopathy. Histopathological examination of the latissimus dorsi muscles showed that the transformation process of the stimulated muscle was good. Thus, severe cardiac dilatation seems to be one of the limitations of cardiomyoplasty. Cardiomyoplasty, when it fails, does not preclude heart transplantation. The histochemical studies confirm the electrophysiologic principle of cardiomyoplasty in humans.

Assisted Circulation↗

PubMed1992

Hormonal regulation of the nuclear localization signals of the human glucocorticosteroid receptor.

Nuclear localization of the rat glucocorticosteroid receptor (rGR) transiently expressed in COS-7 cells appears to be mediated by two nuclear localization signals, NL1 and NL2, in a hormone-dependent mechanism. We investigated the intracellular distribution of the human GR (hGR) expressed in COS-7 cells, by a different immunohistochemical technique involving immunostaining of cell pellet sections, thus avoiding the use of cell permeabilizing agents and allowing rigorous comparison between successive experiments. With a large set of hGR mutants, we could define determinants of the hGR nuclear localization and compare them with those previously reported for rGR. Our study demonstrated two hormone-dependent nuclear localization signals. NL1 activity, overlapping the DNA-binding domain (DBD)-hinge boundary, was repressed by the unliganded ligand-binding domain (LBD), even if the repressed NL1 retained a residual potency to target hGR in the nucleus. Structure/function analysis suggested a bipartite structure of NL1, analogous to that of other nuclear targeting signals (the carboxy-terminal part of DBD between amino acids 478 and 487 and the beginning of the hinge region which includes a basic amino acid stretch between 491 and 498). Upon hormone binding, NL2, located in the LBD, was activated, but was unable by itself to sustain full nuclear localization, which required the derepressed NL1 activity. Only two sequences in the LBD, localized between amino acids 600 and 626 and from amino acid 696 up to the carboxyl-terminal amino acid 777, respectively, were found to inhibit NL1 activity. As previously reported, efficient nuclear retention, mandatory for gene expression, did not required DNA-binding activity. The controversial intracellular localization of the unliganded form of hGR and the role of hsp90 in cytoplasmic localization are further discussed.

Cell Line↗

PubMed1992

A novel monoclonal anti-rabbit hsp90 antibody: usefulness for studies on hsp90-steroid receptor interaction.

The M(r) 90,000 protein associated with steroid receptors in their non-transformed state has been identified as a heat shock protein (hsp90) but the relationship between hsp90 binding and receptor function is still poorly understood. In this work, we have obtained and characterized one monoclonal anti-rabbit hsp90 antibody (7C10), among more than 2000 wells plated. This antibody was able to complex both free and rabbit uterine progesterone receptor-associated hsp90 as demonstrated by sedimentation analysis on sucrose gradients. As assessed by ELISA, 7C10 displayed a high binding affinity for hsp90 (approximately 4 nM). A standardized and specific competitive binding assay was developed for accurate quantification of hsp90 in rabbit tissues including reticulocyte lysate. 7C10 also permitted immunolocalization of hsp90 in various rabbit tissues. In Western blot, the monoclonal antibody recognized a single polypeptide band of M(r) approximately 90,000 in crude or purified rabbit preparations but failed to cross-react with any other mammalian or avian hsp90. These findings suggest that hsp90, a highly conserved protein, is a weak immunogen and elicits a strict species specific immunological response. Owing to its high affinity and specificity for rabbit hsp90, the monoclonal antibody 7C10 was used for purification and total depletion of hsp90 from the reticulocyte lysate, an efficient system for in vitro receptor translation and reconstitution studies. Thus, 7C10 represents a new powerful tool to further investigate the importance of hsp90 in steroid hormone receptor function.

Animals↗

PubMed1992

Long-term results of porcine bioprostheses in the tricuspid position.

Between 1974 and 1990, 58 patients underwent tricuspid valve replacement with porcine bioprostheses (Hancock 42, Carpentier-Edwards 16) during multiple valve replacement (double, 21; triple, 37). Perioperative mortality was 12%; 16 patients died later, mostly from cardiac causes. Actuarial survival (1 patient lost to follow-up) was 81% +/- 11% at 5 years, and 60 +/- 17% at 10 years. Reoperation because of Hancock prosthesis deterioration was performed in 2 patients at 11 and 15 years, respectively. At last follow-up (mean 108 +/- 48 months), 82% of survivors (28/34) were functionally improved. Doppler echocardiography was performed in 29 patients in February 1991. In 21 patients, after 88 +/- 40 months of follow-up, the bioprosthesis was normal, there was no leaflet malformation, no significant tricuspid regurgitation and the mean diastolic transprosthetic gradient (DTPG) was 3.8 +/- 1.7 mmHg. In 7 patients (follow-up: 129 +/- 40 months, P less than 0.05), there was moderate dysfunction (all Hancock prostheses) with leaflet sclerosis, tricuspid regurgitation grade 2, and mean DTPG 5.7 +/- 1.8 mmHg (P less than 0.05). Only 1 patient (Hancock prosthesis implanted in 1981) had severe tricuspid prosthesis stenosis with very thickened leaflets and mean DTPG 13 mmHg. Pulmonary artery hypertension (most often fixed) was present in 11 patients, associated with a poor functional result and a significantly higher DTPG. We conclude that porcine bioprostheses in tricuspid position have an acceptable long-term durability and satisfactory performance. Prosthetic dysfunction correlates with the length of follow-up of patients and with the presence of fixed pulmonary artery hypertension.

Adult↗

PubMed1992

[Coronary accelerated arteriosclerosis and vasospasm in the transplanted heart].

Accelerated atherosclerosis of cardiac grafts is one of the factors limiting long-term survival after cardiac transplantation. The authors report the case of a patient who had a cardiac arrest associated with severe atherosclerosis 18 months after transplantation. The severity of the coronary lesions was underestimated by coronary angiography. An ergometrine test induced coronary spasm, a phenomenon which has only rarely been observed in transplanted hearts. The patient died one month later despite calcium inhibitor therapy. Autopsy revealed very severe triple vessel disease. This case illustrates the possible rapid evolution of coronary artery disease in cardiac transplant recipients, the difficulty in evaluating the severity of the lesions by coronary angiography and the additional possibility of observing coronary spasm in these cases.

Coronary Angiography↗

PubMed1992

[Blood cholesterol and mortality].

Mortality rates vary with serum cholesterol levels: the causal nature of this relationship is studied by prospective studies (analysis of associations) and unifactorial primary prevention trials (experimentation to determine causality). In prospective studies all cause mortality is often increased at low and high cholesterol levels because of the inverse relationships of this factor with cardiovascular mortality (positive) and non-cardiovascular mortality (negative). Coronary death increases proportionally to serum cholesterol levels in all populations, including those with low cholesterol levels, in both sexes and at all ages. The relationship with cerebrovascular mortality seems to depend on the clinical feature: increased mortality rate due to cerebral haemorrhage in patients with low serum cholesterol and a positive correlation with cerebral thrombosis. Mortality due to cancers is generally negatively correlated to serum cholesterol levels with a significant increase in mortality in patients with a low serum cholesterol. This relationship often becomes less significant as the time between measurement and death increases. Mortality due to violent causes is not usually related to serum cholesterol. The multitude of possible causes of confusion makes any causal interpretation of data illusory. Experimentation by unifactorial primary prevention trials is essential for any etiological research but none of the trials performed to date was designed to analyse the effect of lowering serum cholesterol on global or coronary mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1992

[Relations between HDL-cholesterol and cardiovascular diseases].

Many retrospective and prospective epidemiological studies have demonstrated an inverse relationship between HDL-cholesterol and coronary risk. The predictive value of HDL-cholesterol is observed both in asymptomatic subjects and those with a primary vascular event. Several genetic abnormalities may be responsible for low HDL cholesterol (under 100 mg/dl or 0.26 mmol/l) or for a less severe hypoalphalipoproteinaemia. Despite some very low values, these rare causes of HDL deficiency are not all atherogenic and serve to emphasize the complexity of HDL metabolism. The protective role of HDL is explained by a number of mechanisms such as their role in the reverse transport from the peripheral tissues to the liver, their anti-oxidant effect and the increase in prostacyclin levels. The correction of isolated hypoalphalipoproteinaemia by drugs is controversial, but associated hyperlipidaemic states would be an indication to use drugs which increase the HDl-cholesterol the most.

Apolipoprotein A-I↗

PubMed1992

[Role of triglycerides in cardiovascular diseases].

The role of triglycerides in cardiovascular disease is a controversial subject. Despite differences of opinion, present data allow a certain number of conclusions to be drawn. Hyperchylomicronemia is not associated with atherosclerosis, whereas type III hyperlipidemia is very atherogenic. These two abnormalities are, however, rare, and the majority of hypertriglyceridemias are, in practice, associated with increased very low density lipoproteins. Many epidemiological trials do not identify hypertriglyceridemia as an independent risk factor when the cholesterol and, in particular, the HDL cholesterol levels, are taken into consideration. Nevertheless, these results must be interpreted with caution as hypertriglyceridemia represents a very heterogeneous entity which is closely related to many factors which affect coronary risk (hypertension, insulin resistance, sedentarity, and even tobacco consumption). Therefore, hypertriglyceridemia and hypo-HDL-emia may be the result of the same primary abnormality; as the HDL-cholesterol level is more stable, it is the parameter which will be identified as a protective factor in epidemiological trials. The available data is insufficient to affirm that therapeutic lowering of triglycerides is accompanied by a reduced coronary risk because none of the large scale trials were designed to analyse this problem. Despite these epidemiological data, the measurement of serum triglyceride levels remains important in patients with hyperlipidemia.

Cholesterol, HDL↗

PubMed1992

[Serum cholesterol and cancer. Is there a causal relationship?].

Several studies have reported an inverse relationship between serum cholesterol levels and the risk of cancer, especially of the colon (Seven Countries, Framingham, Chicago studies, London Whitehall Study, Paris prospective study, New Zealand Maori, Honolulu Heart Study, Hypertension Detection and Follow-Up Program, ...). For example, in the Multiple Risk Factor Intervention Trial (361 662 men), the global mortality graph was J-shaped, higher at either side of the 4.6-5.1 mmol/l value of serum cholesterol. This increased mortality with lower serum cholesterol levels was due to increased numbers of death from cancer. However, when the relationship is studied with respect to the time elapsed between the cholesterol measurement and death from cancer, the relative risk of death in the lowest decile with respect to the average of the following deciles, decreases with the period between measurement of the serum cholesterol and time of death. The negative relationship between serum cholesterol and death by cancer, very significant for deaths occurring within the first 5 years, disappeared almost completely for deaths occurring after 5 years. Other trials designed mainly to examine cardiovascular risk, and concerning smaller numbers, have not demonstrated this inverse relationship between serum cholesterol and cancer. This negative relationship between serum cholesterol and cancer must be acknowledged. It is weak and concerns mainly colonic cancer, especially in men in the elderly age groups. Several explanations have been put forward: influence of the combination of factors, competition of risk of death by other causes, chance, alteration of normal biological function of the cell membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

[Is regression of atherosclerosis possible?].

Experimental studies have shown the regression of atherosclerosis in animals given a cholesterol-rich diet and then given a normal diet or hypolipidemic therapy. Despite favourable results of clinical trials of primary prevention modifying the lipid profile, the concept of atherosclerosis regression in man remains very controversial. The methodological approach is difficult: this is based on angiographic data and requires strict standardisation of angiographic views and reliable quantitative techniques of analysis which are available with image processing. Several methodologically acceptable clinical coronary studies have shown not only stabilisation but also regression of atherosclerotic lesions with reductions of about 25% in total cholesterol levels and of about 40% in LDL cholesterol levels. These reductions were obtained either by drugs as in CLAS (Cholesterol Lowering Atherosclerosis Study), FATS (Familial Atherosclerosis Treatment Study) and SCOR (Specialized Center of Research Intervention Trial), by profound modifications in dietary habits as in the Lifestyle Heart Trial, or by surgery (ileo-caecal bypass) as in POSCH (Program On the Surgical Control of the Hyperlipidemias). On the other hand, trials with non-lipid lowering drugs such as the calcium antagonists (INTACT, MHIS) have not shown significant regression of existing atherosclerotic lesions but only a decrease on the number of new lesions. The clinical benefits of these regression studies are difficult to demonstrate given the limited period of observation, relatively small population numbers and the fact that in some cases the subjects were asymptomatic. The decrease in the number of cardiovascular events therefore seems relatively modest and concerns essentially subjects who were symptomatic initially. The clinical repercussion of studies of prevention involving a single lipid factor is probably partially due to the reduction in progression and anatomical regression of the atherosclerotic plaque.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1992

[Optimal serum cholesterol and efficacy of methods for lowering cholesterolemia].

Analysis of epidemiological studies enables definition of the optimal serum cholesterol level between 2 and 2.2 g/l (5.2 and 5.7 mmol/l). Higher levels are associated with an exponential risk of coronary artery disease: lower levels should be interpreted with caution because of the J-shaped curve of global mortality reported in several trials. In primary prevention, therapeutic trials have clearly shown that a significant reduction in the number of coronary event may be obtained by lowering the serum cholesterol (15 for every 1,000 patients treated). In trials performed to date this benefit has not resulted in any gain in global mortality. In secondary prevention, the benefits of lowering serum cholesterol on the incidence of coronary disease seems identical in terms of relative risk to that observed in primary prevention. Nevertheless, the benefits in terms of absolute risk are much higher because of the high incidence of coronary mortality in a patient population with a previous coronary event. Thus, for 1,000 patients treated, there are 50 less cardiac events and this is reflected in a reduction of global mortality of about 20 for every 1,000 patients treated.

Cholesterol↗

PubMed1992

[Should men aged 20 to 30 years with hypercholesterolemia be managed in the same way as older men?].

Serum cholesterol intervention studies have been mainly performed in middle-aged men. Is the extrapolation of these results to men aged 20 to 30 years justified? Atherosclerosis is a process which continues throughout life. It is clear that increased serum cholesterol levels are associated with a higher coronary risk. In addition, serum cholesterol levels increase with age up to 60 years old. Do young men obtain the same benefits from medical intervention as older men? Therapeutic trials have been performed in middle-aged men. The increase in life expectancy associated with a 6.7% lowering of the serum cholesterol by life-long dietary restrictions would only be 4 months in 20 year old subjects at high risk (hypertension, smokers, low HDL cholesterol). With a 20% reduction in serum cholesterol, the gain would be 12 months. There is no reason for not extrapolating acquired data in the over 30s to 20 to 30 year old subjects. Due to the fact that young subjects are exposed to the risk for longer periods, it is advisable to treat their hypercholesterolaemia even more seriously than that of older patients.

Adult↗

PubMed1992

[Should hypercholesterolemic women be treated?].

There have been few studies designed to evaluate the problem of hypercholesterolaemia in women despite the fact that, like men, cardiovascular disease is their main cause of death. Serum cholesterol is a risk factor in women, but the increased risk appears at much higher values of serum cholesterol than observed in men. In women, low HDL-cholesterol seems to be the best predictive factor for the occurrence of a coronary event, especially if the triglycerides are raised. The absence of therapeutic data on the treatment of hypercholesterolaemia in women underlines the need for a specific trial to assess the effects of lipid-lowering drugs in this population. The cardiovascular benefits of hormone substitute therapy at the menopause have been reported in several studies and a large scale randomised trial is under way to confirm these results. The benefit of hypercholesterolaemic therapy in women with mild hypercholesterolaemia has not been proved. When the serum cholesterol level is over 3 g/l (7.77 mmol/l), early treatment is advisable.

Adult↗

PubMed1992

[Hyperlipidemia in patients over 60 years old].

The management of hyperlipidemia in individuals aged 60 or over is a serious problem, given the frequency of metabolic abnormalities in this age group. The decision to treat must take into account a number of uncertainties. Hypercholesterolemia is a risk factor in the elderly and, in general, its importance varies like the other major risk factors (hypertension and smoking): the relative risk decreases with age but this decrease in relative risk is associated with an increase in the absolute risk because the prevalence of cardiovascular disease greatly increases with age. The serum cholesterol level increases with age but the physiopathological mechanism os this increase is poorly understood (reduction in the number of LDC receptors?). In the over 70s, serum cholesterol levels decrease, probably because of a selection due to the deaths of subjects at higher risk. No therapeutic trials have been performed to evaluate the effects of lowering the serum cholesterol in the over 60s. In addition, strict application of international recommendations in this age group would result in a large number of therapeutic interventions, the value of which would be questionable. Under these conditions, practical clinical advice is based on reasoned extrapolation of epidemiological data obtained in middle-aged men. Treatment should therefore be reserved for sever forms of hyperlipidemia, taking into consideration the life expectancy of the individual.

Aged↗

PubMed1992

[The facts about cholesterol (condensed translation and comments of the common declaration of AHA and NHLBI)].

Many epidemiological and experimental studies have confirmed the continuous positive relationship between serum cholesterol levels and coronary risk. Therapeutic trials have demonstrated that the lowering of serum cholesterol by diet or drugs can lower this coronary risk. The benefits have been shown in men and women, the young and old, in those with a high coronary risk due to raised serum cholesterol and LDL and those with only moderately increased risk. In addition, therapeutic interventions on serum cholesterol are cost-effective. These observations more than justify the present national program of lowering the serum cholesterol.

Age Factors↗

PubMed1992

[Clinical and hemodynamic prognosis after tricuspid valve replacement with bioprosthesis].

Between 1974 and 1990, 58 patients underwent tricuspid valve replacement with a porcine bioprosthesis (Hancock 42, Carpentier-Edwards 16) in the course of polyvalvular replacement (double 21, triple 37). Early postoperative mortality was 12%: 16 patients died secondarily, usually of cardiac causes. The actuarial survival (1 patient lost to follow-up) was 81 +/- 11% at 5 years and 60 +/- 17% at 10 years. Two patients were reoperated for dysfunction of a Hancock bioprosthesis, 11 and 15 years after implantation. At long-term, with an average follow-up of 108 +/- 48 months, 82% of survivors (28/34) were clinically improved. Doppler echocardiography was performed in 29 patients in February 1991. In 21 cases, with a follow-up of 88 +/- 40 months, the bioprosthesis was normal with an average diastolic transprosthetic pressure gradient of 3.8 +/- 1.7 mmHg. In 7 patients followed up for 129 +/- 40 months (p < 0.05) moderate dysfunction of the Hancock prosthesis was observed with a mean diastolic pressure. Severe dysfunction of a Hancock prosthesis was observed in 1 case. Fixed pulmonary hypertension was noted in 11 cases and was associated with a poor clinical result and a raised mean diastolic transprosthetic pressure gradient. The durability and haemodynamic performance of tricuspid porcine bioprostheses are satisfactory in the long term. Prosthetic dysfunction is correlated to the duration of implantation of the bioprosthesis and to persistent pulmonary hypertension.

Actuarial Analysis↗

PubMed1992

[Myocardial infarction beyond the 48 first hours: treatment with calcium channel antagonists].

Calcium channel blocking agents prevent calcium entering cardiac and smooth muscle cells. With reduction of the blood pressure, heart rate and myocardial contractility, they reduce myocardial oxygen demand. By relieving spasm and coronary constriction, and dilating the collateral coronary vessels, they improve perfusion of the ischemic zones. The results in experimental infarction are contradictory: the reduction in the infarct size and ischaemia is not constant. In the Myocardial Infarction Study, a trial of lidoflazine in 1792 subjects followed up for an average of 5 years, there was no significant difference between the mortality rates of the two groups. In the Danish Verapamil Infarction Trial I, which included 436 subjects receiving 360 mg/day of verapamil or placebo, the 6 months mortality was less (NS) in the verapamil group (12.8%) than in the placebo group (13.9%) as was the reinfarction rate (7.8% versus 9.2%; NS). In the DAVIT II trial of 1775 subjects, treatment was introduced 9 +/- 2.7 days after admission. Mortality was lower (NS) in the verapamil group (11.1%) than in the placebo group (13.8%) and the recurrences were less common (p = 0.04) in the treatment group (11.0%) than with placebo (13.2%). The Secondary Prevention Reinfarction Israeli Nifedipine Trial is a comparison of Nifedipine 30 mg/day and placebo introduced 7-21 days after infarction in 2276 subjects. After 10 months, the mortality and reinfarction rate were similar in both groups, as in the SPRINT II trial (60 mg/day of nifedipine or placebo) at 6 months. In the Multicenter Diltiazem Postinfarction Trial of 2466 patients, Diltiazem 240 mg/day or placebo was administered 3 to 15 days after infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

[Which anti-ischemic treatment can be prescribed during and after the acute phase of myocardial infarction?].

After myocardial infarction, calcium channel blockers are the most prescribed anti-ischemic drugs followed by nitrate derivatives and beta blockers. In order to assess whether this attitude is justified by published data on their efficacy, a meta-analysis of trials of anti-ischemic drugs in myocardial infarction was performed. The early mortality was 13.3% in the group treated by IV nitrates in the acute phase of myocardial infarction and 17.2% in control groups, reducing the risk by a quarter (95% confidence interval of the odds ratio (CI): 0.55-0.95). When all nitrate derivative trials were grouped together, the reduction in the risk of death of 21% was significant (from 15% to 11.8%) (CI: 0.59-0.94). Although oral nitrate derivatives introduced during the acute phase and continued for several weeks induced a non-significant reduction in mortality of 16%, when given intravenously, the benefits on early and longer term mortality were unquestionable. The mortality was 9.8% in the groups treated by calcium channel blockers and 9.3% in control groups (NS); the recurrent infarct rate was 4.8% and 5.4% respectively (NS). In this family of drugs, there was no product which distinguished itself from the others with regard to beneficial or adverse effects. The early mortality decreased from 9.2% to 8.2% in the groups treated by oral beta-blockade--a risk reduction of 10% (NS) and from 4.2% to 3.7% with intravenous beta-blockers--a risk reduction of 12% (p = 0.03). Late mortality decreased from 9.4% to 7.6%, a reduction of 20% (p < 0.00001) in long term trials.2+ contraindication of betablockers in patients without cardiac failure.

Adrenergic beta-Antagonists↗