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J P Collet

Publications and source records attributed to J P Collet.

At least 73 records · Page 4Linked to original sources
PubMed1996

Fibrinogen Dusart: electron microscopy of molecules, fibers and clots, and viscoelastic properties of clots.

Ultrastructural perturbations resulting from defects in polymerization of fibrinogen Dusart, a congenital dysfibrinogenemia with the amino acid substitution A alpha 554 arginine to cysteine, were investigated by a variety of electron microscope studies. Polymerization of this mutant fibrinogen on addition of thrombin is impaired, producing clots with decreased porosity and increased resistance to fibrinolysis, resulting in thrombotic complications in the family members with this dysfibrinogenemia. Electron microscopy of rotary-shadowed individual molecules revealed that, in contrast to control fibrinogen, most of the alpha C domains of fibrinogen or fibrin Dusart appeared to be free-swimming appendages that do not exhibit intra- or intermolecular interactions either with each other or with the central domains. The location of albumin on the alpha C domains was demonstrated by electron microscopy using anti-albumin antibodies. Electron microscopy of negatively contrasted fibrin Dusart fibers indicated that they were less ordered than control fibers and had additional mass visible. Electron microscopy of freeze-dried, unidirectionally shadowed fibers showed that they were twisted with a shorter pitch. Scanning electron microscopy revealed that intact clots were made up of thin fibers with many branch points and very small pore sizes. The viscoelastic properties of Dusart fibrin clots measured with a torsion pendulum indicated a marked increase in stiffness consistent with the structural observations.

Biomechanical Phenomena↗
PubMed1996

Comparison of the effect of inhaled nitric oxide and intravenous nitroglycerine on hypoxia-induced pulmonary hypertension in pigs.

Pulmonary hypertension is usually treated with intravenous (i.v.) vasodilators, but their use is limited by systemic effects. In the current study, we compared the effects of inhaled nitric oxide and intravenous nitroglycerine on pulmonary and systemic haemodynamic responses as well as on gas exchange measurements in anaesthetized pigs whose pulmonary pressure was increased by hypoxia (FiO2 = 15%). Both treatments reduced pulmonary pressure to the control level. Inhaled nitric oxide did not affect systemic arterial pressure but intravenous nitroglycerine decreased it from 126.2 to 108.8 mmHg (P = 0.04). Unlike intravenous nitroglycerine, inhaled nitric oxide increased arterial PaO2 from 5.3 to 5.9 kPa (P = 0.02). Both treatments diminished central venous pressure and left atrial pressure, suggesting a possible cardiac effect. Inhaled nitric oxide was shown to be a potent pulmonary vasodilator which attenuated pulmonary hypertension and improved arterial oxygenation without important direct effects on systemic pressure in porcine hypoxia-induced pulmonary hypertension.

Administration, Inhalation↗
PubMed1996

Regulation of fibrinogen biosynthesis by cytokines, consequences on the vascular risk.

High level of fibrinogen in plasma is recognised as an important vascular risk factor. However, it is not known if the increase in fibrinogen is directly responsible for the vascular risk or is a marker of vascular inflammation. Our data strengthen the hypothesis that the fibrinogen level is a marker of vascular disease, since a parallel effect of cytokines on fibrinogen biosynthesis and on vascular injury was noted. Among the cytokines which induce the synthesis of fibrinogen, oncostatin M (OSM) is the most potent cytokine synthesised by activated monocytes for inducing fibrinogen synthesis by Hep G2 cells (human hepatoma cell line). Interestingly at the same concentrations needed for fibrinogen biosynthesis, OSM induces smooth muscle cell proliferation. In contrast, the cytokines IL-4, IL-10 and IL-13 which have a protective effect against vascular injury leading to atherosclerosis, dose dependently down regulate the biosynthesis of fibrinogen. This was due to both a decrease of IL-6 induced fibrinogen synthesis by hepatocytes, evidenced by a decrease in fibrinogen secretion in the medium and beta chain mRNA expression and to an inhibition of production of the hepatocyte-stimulating activity for fibrinogen biosynthesis (HSF) by LPS-activated monocytes. Noteworthingly, IL-10 induces a significant decrease of the production of OSM by LPS-activated monocytes. In situ activation of monocytes by cytokines in the vessel wall could also contribute to the deposition of fibrin(ogen) derivatives, identified as pathogenic factor.

Arteriosclerosis↗
PubMed1995

A randomized comparison of the effect of four antihypertensive monotherapies on the subjective quality of life in previously untreated asymptomatic patients: field trial in general practice. The OCAPI Study Group. Optimiser le Choix d'un Anti-hypertenseur de Première Intention.

OBJECTIVE: To assess the equivalence of four antihypertensive treatments in patients with mild-to- moderate hypertension, and to compare the effects of those drugs on the subjective quality of life and clinical safety. DESIGN, SETTING AND PATIENTS: 653 patients aged > or = 18 years with untreated hypertension were randomly allocated to receive a combination of two diuretics (altizide and spironolactone), a beta-blocker (bisoprolol), a calcium antagonist (verapamil), or an angiotensin converting enzyme (ACE) inhibitor (enalapril). Follow-up lasted for 1 year. MAIN OUTCOME MEASURES: A composite outcome of the following measures was used to define success: attendance at the 12-month visit; at least nine supine DBP measurements during the study; and median supine DBP < 90 mmHg and a reduction of at least 10 mmHg compared with the baseline value. Failure was defined as one or more of those criteria not being fulfilled. Equivalence was concluded if the 95% confidence interval for the success rates differed between two groups by less than +/- 10%. Clinical safety and subjective quality of life were also assessed. RESULTS: No statistically significant differences in the change in DBP or systolic blood pressure were observed between the groups. The success rates were 43.9, 42.0, 32.5 and 43.9% in diuretic, beta-blocker, calcium antagonist and ACE inhibitor groups, respectively. Equivalence between the treatments could not be concluded, although analysis with a larger equivalence interval showed that some comparisons indicated equivalence. Significant improvement in satisfaction was observed for certain items for subjective quality of life at 1 month in the calcium antagonist treatment group, and significant differences in the responses to the clinical safety questionnaire were observed after 1-month follow-up in calcium antagonist and beta-blocker groups. Differences were no longer significant after 9 months. CONCLUSIONS: These results do not provide evidence on the basis of efficacy of blood pressure lowering or ability to increase short-term (1-year) safety and quality of life favouring any particular treatment among the studied drugs for newly diagnosed patients with mild-to-moderate hypertension.

Adolescent↗
PubMed1995

Education program for general practitioners on breast and cervical cancer screening: a randomized trial. PRE.SA.GF Collaborative Group.

This study was aimed at evaluating the effects of an education program for general practitioners on their prescribing behaviour for cervical and breast cancer screening tests, and assessing the feasibility of general practitioners participation in screening programs. All three cytology laboratories and 19 of the 20 radiologists in one administrative region ("Haute-Savoie") in France agreed to participate. The 278 general practices in this region were randomly assigned to either the intervention group (a one-day seminar on screening for breast cancer and cervical cancer) or the control group (n for both = 139). The prescriptions of tests for the following year were noted from the laboratories' and radiologists' records. No significant differences were observed between the intervention group and the control group for the number of mammographies prescribed with a mean of 19.3 and 15.2 per practice, respectively. However, significantly more mammographies were prescribed in women aged over 50 by the intervention group (p = 0.038). Inversely, fewer smear tests were prescribed in the intervention group (mean per practice: 40.5 and 46.1, respectively). A significantly higher number of practices in the intervention group did not prescribe any smear tests (p = 0.007). This study suggests that it is possible to influence general practitioners' participation in screening programs, but that the messages should be carefully presented, since negative effects are possible.

Adult↗
PubMed1994

Survey of the attitudes to management of acute pyelonephritis in children. GEP.

Although urinary tract infections are of particular concern in young children, as they may lead to permanent health problems, there is no consensus for their acute management. We carried out a mailed survey of 455 general practitioners, 143 paediatricians (randomly selected from a list of physicians in the Rhône-Alpes region of France) and 45 paediatric nephrologists (all the members of the "Société de Néphrologie Pédiatrique") to examine their attitudes to the management of a fictitious case of a young girl with symptoms indicative of acute pyelonephritis. The responses given by the general practitioners and paediatricians were similar, whereas those given by the paediatric were similar, whereas those given by the paediatric nephrologists were often different, for example 20% of the general practitioners and 17% of the paediatricians said they would hospitalize the child, compared with 69% of the paediatric nephrologists. The majority of the general practitioners and paediatricians favoured single oral antibiotic therapy, whereas the paediatric nephrologists were split between single and combined antibiotic therapy, but preferred intravenous administration. The most frequently prescribed drug was a penicillin. The heterogeneity of the results from this survey stresses the need for the assessment of various strategies in terms of their efficacy for preventing kidney scarring and their risk-to-benefit ratios in well-designed randomised controlled trials.

Acute Disease↗
PubMed1994

Risk of infectious diseases in children attending different types of day-care setting. Epicrèche Research Group.

This population-based prospective cohort study compared the risk of recurrent infections in children attending family day care (< or = 3 children per family), small (10-20 children) day-care centers (DCCs), and large (> or = 40 children) DCCs. The parents of a total of 1,242 children participated in the study (97% of the families initially contacted). An infectious episode was defined as the acute occurrence of a new symptom lasting for at least 48 h and resulting in specific treatment. Two episodes were counted as such only if they were separated by a symptom-free week. Surveillance was under the responsibility of a nursing director and was similar for all three types of DCCs. During the 8.5-month follow-up period, 3,639 infectious episodes were recorded. Compared to those in family day-care, children attending small DCCs presented a higher risk for > or = 6 total infectious episodes [odds ratio (OR) = 2.4; 95% confidence interval (CI) = 1.6-3.7]; > or = 5 upper respiratory tract infections (OR = 2.2; 95% CI = 1.4-3.4); > or = 2 episodes of otitis media (OR = 2.6; 95% CI = 1.0-2.6); > or = 2 episodes of conjunctivitis (OR = 4.1; 95% CI = 2.1-8.2); and > or = 2 episodes of croup (OR = 4.1; 95% CI = 1.6-10.9). The risk for children attending large DCCs was intermediate between those in family day care and those in small DCCs.(ABSTRACT TRUNCATED AT 250 WORDS)

Child Care↗
PubMed1994

OM-85 BV: primary versus secondary prevention.

Recurrent upper respiratory tract infections in children have an important socioeconomic impact, with consequences on both the quality of life of the children, the possible medical sequelae and the inherent direct and indirect costs. The possibility to prevent these infections is limited in the absence of specific vaccines against microorganisms responsible for most of the respiratory tract infections (i.e. respiratory syncitial virus, adenovirus, rhinovirus). Immunoactive bacterial extracts that stimulate the nonspecific component of the immune system may protect against a large variety of microorganisms that enter the body by the oral and respiratory pathway; they may, therefore, play an important role with regard to this preventive action. OM-85 BV is an IBE that has been used in children who suffer from repeated infections to prevent the occurrence of new episodes (secondary prevention). In this condition, the drug has been shown to be effective in protecting children against recurrent airway infections. Its use as a primary preventive agent to prevent the development of repeated infections in children attending day-care centers (a very high-risk environment for repeated infections), however, did not show a similar efficacy. The risk of having > or = 4 episodes of upper respiratory tract infections over a period of 7.5 months was 26.7% in the verum group and 33.8% in the placebo group (relative risk 0.79, confidence interval 0.59-1.06]. In an exploratory analysis concentrating on the 3-month treatment period, however, a 48% reduction of the risk of presenting > or = 3 episodes was observed. Furthermore, this exploratory analysis showed a strong correlation between drug efficacy and age of the children.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1994

Epidemiology of viral infections and evaluation of the potential benefit of OM-85 BV on the virologic status of children attending day-care centers.

Viral investigations were performed during 4 winter seasons (88/89, 89/90, 92/93, 93/94) in children attending day-care centers (DCCs) in the Rhône Département in eastern France. Over the total observation period of 4 winter seasons, 780 children were screened with a nasal swab for the presence of viruses. Of those, 230 (29.5%) had a positive viral culture. The viruses identified were respiratory syncytial virus (RSV), influenza A and B virus, parainfluenza virus, coronavirus, rhinovirus, adenovirus and enterovirus. During that time, 83 epidemic events in 47 DCC were recorded. A particular virus was judged to be causally related to an epidemic if the identical virus was isolated in > or = 3 children during the same outbreak of respiratory diseases. Thus, in 51 cases (61.4%) of all epidemics, the following viruses were responsible for an epidemic: RSV (n = 23), coronavirus (n = 10) (only during the season of 1993-1994), influenza A virus (n = 6), rhinovirus (n = 4), enterovirus (n = 4), adenovirus (n = 3) and parainfluenza virus (n = 1). Except for the somewhat surprising accumulation of coronavirus epidemics during the winter of 1993-1994, there were only minor seasonal variations from one year to another. As expected, RSV accounted for about one third of all respiratory tract infections in children attending DCCs and was therefore the most important single causative agent. These results are compared with data from children who did not attend a DCC and were cared for in a private practice.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1993

Dusart syndrome: a new concept of the relationship between fibrin clot architecture and fibrin clot degradability: hypofibrinolysis related to an abnormal clot structure.

Fibrinogen Dusart is a congenital dysfibrinogenemia (A-alpha 554 Arginine-->Cysteine) associated with severe thrombotic disorder, high incidence of thrombotic embolism, and abnormal fibrin polymerization. This thrombotic disorder was attributed to an abnormal clot thrombolysis with reduced plasminogen binding to fibrin and defective plasminogen activation by tissue plasminogen activator. The purpose of this work was to assess whether clot architecture could be involved in the thromboresistance of the fibrin Dusart and the high incidence of embolism. An important change in Dusart fibrin clot structure was identified with dramatic decrease of gel porosity (Ks), fiber diameters (d), and fiber mass-length ratios (mu) derived from permeation analysis. In addition, rigidity of the Dusart clot was found to be greatly increased compared with normal fibrin. We provide evidence that both thrombolysis resistance and abnormal rigidity of the fibrin Dusart are related to this abnormal architecture, which impairs the access of fibrinolytic enzymes to the fibrin and which is responsible for a brittle clot that breaks easily, resulting in a high incidence of embolism. Indeed, when restoring a normal clot structure by adding dextran 40 (30 mg/mL) before coagulation, clot thrombolysis and clot rigidity recovered normal values. This effect was found to be dose-dependent. We conclude that clot architecture is crucial for the propensity of blood clot to be degraded and that abnormal clot structure can be highly thrombogenic in vivo. The alpha-C domains of fibrinogen are determinant in fibrin clot structure.

Dextrans↗
PubMed1993

An effect model for the assessment of drug benefit: example of antiarrhythmic drugs in postmyocardial infarction patients.

An effect model is a function that defines the relationship between the clinical efficacy of a treatment and specific covariates. The simplest effect model defines the probability of failure in treated patients as a linear function of the probability for these patients if they received no treatment. We used this approach to explore the effects of Class I antiarrhythmic agents in patients after myocardial infarction. Evidence from one large trial, the Cardiac Arrhythmic Suppression Trial (CAST), and the pooling of data from several smaller trials suggests that these agents have harmful effects in postmyocardial infarction patients. The relevance of results from pooled data is dependent on the homogeneity of the trials and is assessed by a heterogeneity test that is dependent on the analytical method used, i.e., odds ratio or rate difference methods, which correspond to two different effect models. We have developed an effect model that considers both iatrogenic effects of these drugs, i.e., depression of ventricular function and arrhythmogenic effects. When applied to the data from 13 published trials (including CAST), we found that these drugs may be beneficial in high-risk patients (with a 1-year mortality rate of > or = 15%) and that the background lethal iatrogenic effect is likely to affect low- and very low-risk patients (1-year mortality rate of < or = 5%). The accuracy of the proposed model was confirmed with use of the results from the recent CAST II study.

Anti-Arrhythmia Agents↗
PubMed1993

Stimulation of nonspecific immunity to reduce the risk of recurrent infections in children attending day-care centers. The Epicrèche Research Group.

A randomized, double blind, placebo-controlled clinical trial was performed in 423 children attending day-care centers to assess whether stimulating nonspecific immunity would reduce the incidence of recurrent infections. The drug used for the trial (Imocur) is an extract obtained from eight different species of bacteria. At the end of the total follow-up period (3 months with treatment and 4.5 months without), the risk for > or = 4 episodes of upper respiratory infections was not significantly lower in the treated group than in the placebo group (26.7% vs. 33.8%, relative risk, 0.79; 95% confidence interval, 0.59 to 1.06). In an exploratory analysis limited to the 3-month treatment period, however, we observed a 48% reduction in the risk of presenting > or = 3 episodes of upper respiratory infections: 9.5% vs. 18.3%, respectively, in the treatment group and the placebo group (relative risk, 0.52; 95% confidence interval, 0.31 to 0.86). Similar results were found for the risk of > or = 1 episode of gastroenteritis. We also observed a strong correlation between the drug efficacy and age; this observation is coherent with the underlying pathophysiologic model in which the immune system matures with age.

Adjuvants, Immunologic↗
PubMed1993

[Prevalence of nocturnal enuresis in school-age children].

Bed-wetting is a frequent feature in school-age children. A pilot transversal study was carried out in school-children from the city of Villeurbanne in order to study the prevalence of bed-wetting in school-age children. Answers to a questionnaire were exhaustively obtained from 1,677 children in primary school before school-camp. An other questionnaire was given to parents of children from nursery-school: answers were obtained for 386 children, i.e. 95% of the sample. The rate of children suffering from bed-wetting was 49% between 3 and 4 years of age, 4% between 7 and 6 years of age and 1% between 11 and 12 years of age. These results are comparable to those reported in the literature. Within the range 4-7 years of age, the estimation of bed-wetting exhibited a lower frequency in the school-camp questionnaire probably reflecting its speculated social inconvenience, as compared with the answers to the nursery-school questionnaire rather reflecting a close estimation of property attainment. The reported prevalence rates provided no discriminant criteria regarding the mechanism of bed-wetting.

Age Factors↗
PubMed1993

[Fibrinogen, a vascular risk factor].

Epidemiological studies have consistently correlated plasma fibrinogen level to the risk of coronary heart disease (CHD) and acute ischemic stroke. Several mechanisms have been proposed such as the role of fibrinogen in the viscosity of blood, the participation of fibrinogen in both fibrin clot formation and platelet aggregation. However, there is no evidence that the increase in fibrinogen is directly responsible for the vascular disease since the cytokines which participate to the synthesis of fibrinogen by the hepatocytes, such as interleukin 6, could also induce an endothelial cell damage by increasing tumor necrotic factor (TNF) production. In these conditions fibrinogen increase could therefore only represent a marker of cytokine production which in turn is responsible for vascular injury. In addition, for the pathogenesis of atherosclerosis, the influence of fibrinogen is not only mediated by way of increased fibrinogen concentration but could be due to a structurally variant fibrinogen. The recent epidemiological studies have shown that the variation at the beta locus of fibrinogen is associated with an increase risk of peripheral atherosclerosis. The finding concerning dysfibrinogenemia and thrombosis (Dusart and Tampere) create further opportunities to enrich knowledge of the link between the association of abnormal gel structure and thrombotic diseases such as myocardial infarction or stroke at young age. This abnormal clot structure could contribute to thrombogenicity by decreasing the capacity of these clots to be degraded by fibrinolytic enzymes or by decreasing thrombin binding since fibrin is considered as a "thrombin trap".(ABSTRACT TRUNCATED AT 250 WORDS)

Fibrinogen↗