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Biomedical subjects

D Thomas

Publications and source records attributed to D Thomas.

At least 559 records · Page 31Linked to original sources

[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↗

[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↗

[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↗

[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↗

[Diagnostic and therapeutic strategy in patients with multiple arterial disease].

Concomitant coronary and peripheral lesions are common, in particular in candidates for peripheral surgery. Coronary lesions dominate the prognosis in all cases. The later mid- and long-term risks of such associations is far greater than the immediate operative risk. Each type of surgery, peripheral or coronary, offers the opportunity for arterial evaluation of the other area in its own right, rather than because of the surgical context. No invasive investigations should be routine. The diagnostic approach is guided by clinical data and to a lesser degree by non-invasive investigations, the discriminant nature of which is unfortunately poor in the context of coronary evaluation. Indications for multifocal simultaneous or sequential revascularization procedures, by surgery or angioplasty, are in fact small in number. They are wide ranging and must be discussed case by case, taking into account age, general condition, the emergency context and the type and severity of lesions.

Arterial Occlusive Diseases↗

[VVI mode cardiac pacing: cause or risk factor of cerebral embolism?].

Epidemiological studies suggest that VVI pacing is associated with a higher risk of embolic complications than atrial or dual chamber pacing. However, no studies have been performed on pacemaker patients admitted to a neurological department with a cerebral embolism. The authors report the cases of 8 patients (6 men and 2 women) with an average age of 74 years and having the following characteristics: 1) a cerebral embolism, 2) a permanent cardiac pacemaker (7 VVI and 1 DDD mode). The average delay between implantation of the pacemaker and the neurological complication was 31 months. Cardiological investigations at the time of admission showed: a clinically evident cause of cardiac embolism in 3 cases (2 with VVI and 1 with DDD pacing); paroxysmal or permanent atrial fibrillation in 4 cases with VVI pacing at the time of the embolic event (in only one case at the time of implantation); various echocardiographic abnormalities in 6 of the 7 patients who underwent this examination, mainly left atrial dilatation (6/7), septal wall motion abnormalities in all related to ventricular pacing and unexplained left ventricular dilatation in 2 patients with VVI pacemakers. These results suggest that although the etiology of cerebral embolism was probably multifactorial in some patients, VVI packing probably a predisposing role, though not the only cause, and could be considered to be an embolic risk factor as suggested by previous epidemiological studies. These preliminary retrospective data should be interpreted cautiously taking into account the small population size. Prospective studies on pacemaker patients with cerebral embolism are required.

Aged↗

[Peripheral calcific embolism after percutaneous mitral valvuloplasty].

The authors report a case of calcific embolization after percutaneous mitral valvuloplasty. The nature of the embolism was confirmed by anatomopathological examination after popliteal embolectomy. This complication would appear to be extremely rare but represents an additional risk in patients with calcific mitral stenosis.

Adult↗

Half a loaf is better than waiting for the bread truck. A computerized mini-medical record for outpatient care.

We describe a locally developed system for partial computer storage of medical data, called the mini-medical record system. The system produces a typed face sheet prior to each patient visit. The face sheet, which also serves as a progress note, contains patient demographic data, medical problem lists, previous vital signs, allergies, medication profile, and health maintenance reminders. Between regularly scheduled visits, all computerized data are available by computer printout for unscheduled visits to walk-in clinics and the emergency department. Structured reports are generated by the system that describes each resident and faculty members' practice. Quality assurance reports are also available. Since the system draws from several already existing databases, new data entry requirements are modest and cost to the institution is low. Partially computerized systems can be developed inexpensively and are well received in multispecialty practices, where interphysician communication is vital.

Ambulatory Care Information Systems↗

[Value of antimyosin monoclonal antibody scintigraphy in the diagnosis of acute myocardial infarction].

A 53 year old woman developed chest pain with transient anterior subepicardial ischaemic ECG changes and a mild increase in serum myocardial enzyme concentrations. She was admitted to hospital some time later but there were no electrocardiographic signs of infarction. Echocardiography was considered to be normal. Coronary angiography showed no significant stenosis and there were no segmental wall motion abnormalities on left ventriculography. The diagnosis of a non-Q wave infarct was confirmed by myocardial scintigraphy using antimyosin monoclonal antibodies labelled with Indium 111. The site and size of the necrosis were also determined by this non-invasive investigation.

Antibodies, Monoclonal↗

Modulation of lipase hydrolysis and synthesis reactions using carbohydrates.

A novel method for modulation of lipase hydrolysis and synthesis lipase was investigated by using carbohydrates in the microenvironment of the Candida rugosa enzyme. The influence of the addition of different sugars to the previously dialysed enzyme was tested on the two reactions. Rates of hydrolysis were lowered by using dialysed enzyme but were increased after sugar addition, regardless of the identity of the added sugar. In contrast, synthesis reaction rates depended on the nature of the carbohydrate. Rates were increased by adding lactose, which is not a water activity depressor, but were lowered by adding fructose, glucose, sucrose or sorbitol, which are all water activity depressors.

Candida↗

Developmental changes of acidic fibroblast growth factor (aFGF) transcription and expression in mouse brain.

In order to increase our knowledge of the in vivo role of acidic fibroblast growth factor (aFGF) in the central nervous system, we have examined aFGF levels during mouse brain development. Using a specific polyclonal antibody raised against aFGF, we measured levels of aFGF-immunoreactive material (IRMaFGF) in extract of total mouse brain taken at different days of development. We found that the level of measurable IRMaFGF remained low and without significant variation during fetal brain development (0.2 ng/mg of extracted proteins). During the first 11 days postnatal (P0 to P11), IRMaFGF increased from 0.5 to 1.5 ng/mg. Between P11 and P14 IRMaFGF levels went up more rapidly, reaching 5 ng/mg. From P30 to adulthood a constant value of 2.5 ng/mg was measured, aFGF content in the different brain extracts was further characterized by its affinity for heparin-Sepharose, its elution at 1 M NaCl from this column and its capacity to induce thymidine incorporation in quiescent fibroblasts. These results were confirmed at the mRNA level. Northern blot analyses of poly A+ mRNA from brains with a specific riboprobe for bovine aFGF, revealed a major 4.5-Kb transcript and a minor 2.7-Kb transcript detectable only in postnatal brains. A similar pattern to that observed for IRMaFGF was seen with these mRNA transcripts, indicating that these aFGFmRNA are translated in the mouse brain. Our results suggest that aFGF may act in the postnatal phases of brain maturation.

Animals↗

Modulation of protease specificity by a change in the enzyme microenvironment. Selectivity modification on a model substrate, purified soluble proteins and gluten.

Subtilisin BPN' activity on a synthetic substrate is found to decrease with the concentration of soluble additives such as sugars and polyols, the catalytic efficiency of the enzyme being related to the water activity in the reaction medium. Limited hydrolysis of B chain of insulin is followed and the cleavage priority determined. When carried out in glycerol-containing medium, both enzyme catalytic behaviour and specificity are perturbed; a different cleavage order and a selectivity restriction are observed. The experiments were generalised to purified proteins and to an insoluble protein complex. The hydrolysis kinetics of purified gliadins by pepsin and of gluten by a Bacillus neutral protease are modulated in presence of water activity depressors. Glycerol is able to increase both pepsin efficiency and gluten protein solubility. The hydrolysis order is affected by water-structuring molecules in the enzyme microenvironment and new peptides appear whatever the size and initial solubility of the substrate.

Amino Acid Sequence↗

Glutathione levels during thermal induction of the yeast-to-mycelial transition in Candida albicans.

Glutathione (GSH) levels were directly monitored by reverse phase HPLC during the thermal yeast-to-mycelial induction of Candida albicans. The GSH levels decreased approximately 100-fold within 120 min which corresponded to the time of maximal yeast-to-mold conversion. The yeast to mold conversion was inhibited by 1-p-chlorophenyl-4,4-dimethyl-5-diethylamino-1-penten-3-one (CDDP), a thiol-specific alkylator, which prevented the decline in GSH levels. These results are discussed with respect to the potential involvement of intracellular GSH levels in regulation of the yeast-to-mold dimorphism in Candida albicans.

Candida albicans↗

Identification of the structural gene for glucose-6-phosphate dehydrogenase in yeast. Inactivation leads to a nutritional requirement for organic sulfur.

Cloning of the MET19 gene revealed that it encodes the glucose-6-phosphate dehydrogenase from yeast. Sequence analysis showed a high degree of similarity between the yeast and the human enzymes. The cloned gene has allowed the construction of a glucose-6-phosphate dehydrogenase null mutant. The only phenotype of such a strain is an absolute requirement for an organic sulfur source, i.e. methionine, S-adenosylmethionine (AdoMet), cysteine, glutathione or homocysteine. The phenotype of this null mutant raises some new questions about the exact functions of the pentose phosphate pathway which was usually considered as the main cellular source of NADPH. Moreover, results reported here show that an increase of the AdoMet pool represses the transcription of the glucose-6-phosphate dehydrogenase gene. This regulation acts on the glucose-6-phosphate dehydrogenase biosynthesis but does not affect the synthesis of 6-phosphogluconate dehydrogenase. That AdoMet controls a part of the pentose phosphate pathway sheds new light on mechanisms regulating the relative fluxes of carbon utilization through the pentose phosphate pathway and glycolysis.

Amino Acid Sequence↗