Biomedical subjects
Publications and source records attributed to C Bruneau.
A new dicoumarinyl ether, rutamontine and two rare furocoumarins, heraclenol and isopimpinellin, were isolated from Ruta montana. The structure of rutamontine as 6-hydroxy-7-methoxy-3,7'-dicoumarinylether was determined by spectroscopic methods.
BACKGROUND AND OBJECTIVES: Introduction of bacteria into blood components at the collection stage seems to be a frequent occurrence. We therefore assessed determinants of bacterial contamination of whole-blood donations to gain insight into contamination mechanisms and direct prevention. MATERIALS AND METHODS: A cross-sectional study was carried out on donors accepted for whole-blood donation in four French blood banks. Each blood bank used its own two-stage procedure for phlebotomy site preparation. Contamination was identified by culturing two 15-ml samples (collected aseptically at the outset of donation) in a BacT/Alert 240 system. Determinants were assessed by logistic regression analysis. RESULTS: Bacterial contamination, mainly by skin flora, occurred in 76 (2.2%) out of 3385 donations. Significant determinants were as follows: the blood bank (odds ratio [OR] range = 3.0-5.6, P < 0.001); lack of repetition of scrub (OR = 2.7, P = 0.032); and donor age > 35 years (OR = 1.8, P = 0.036). CONCLUSION: Systematic scrub repetition should be implemented to reduce bacterial contamination by skin flora at the collection stage. Further research is required to clarify the role of different antiseptic agents and of donor age.
BACKGROUND: Transfusion-related bacterial contamination is a serious problem. The introduction of bacteria into donations at the collection stage seems frequent, despite well-conducted phlebotomy site preparation. Additional preventive measures are required. STUDY DESIGN AND METHODS: The aim of this study was to assess the potential efficacy of excluding the first 15 mL of blood to reduce the bacterial contamination of donations. A special device allowed the aseptic collection of two samples at the beginning of donation: S1 (first 15 mL) and S2 (next 15 mL). Bacteriologic cultures of S1 and S2 were performed by using an automated system. The procedure's efficacy was measured by the proportion of positive donations in S1 that were then negative in S2. RESULTS: S1 and/or S2 were positive in 76 (2.2%) of 3385 donations. In about three-fourths of the culture-positive donations, contamination was detected in the first 15-mL sample only. Gram-positive cocci accounted for 81 percent of species, gram-positive bacilli for 14 percent, and gram-negative bacilli for 5 percent. The new procedure would have prevented the introduction of bacteria in 55 donations, reducing to 0.6 percent the risk of contamination from the first 15 mL collected. CONCLUSION: Although the final effect on blood component bacterial contamination rates cannot be derived from the study, excluding the first 15 mL of blood may reduce the rate of bacterial contamination in donations.
BACKGROUND: Boulogne-Billancourt database is in France the only permanent and specific childhood injury surveillance system. Integrated in an safe community program designed by the World Health Organization (WHO), the aims of a local database are to provide precise information intended to implement prevention actions. METHOD: All children less than sixteen years old living in Boulogne-Billancourt, victims of injuries occurring in that town, and requiring hospital care, are targeted. RESULTS: Two thousand five hundred and eighty accidents have been computed between 1(st) January 1998 and 31 December 1999, i.e. an average annual incidence of 79.7/1000 children. As in other similar databases, domestic accidents are prevalent in the average (40%), even though after five years old school injuries become the most frequent ones (36%). Falls are the main mechanism involved in injury at any age (44 to 54%). Distribution of other mechanisms varies with respect to age: foreign body prevalence is maximum between one and four (2.5%), struck-collisions (38%) between ten and fifteen years old. A significant increase of falls involving roller-skates or skateboards has been observed between 1998 and 1999 (3.8% versus 1.1%, p<0.001). Predominanting injury causes are contusions (38%), mainly head trauma (10%), open wounds (16%), fractures (10%), and sprains (6%). Two hundred and twenty four injuried children have been admitted in 1998, 205 in 1999, i.e. respectively 13.8/1000 and 12.7/1000 children dwelling in Boulogne. Overall recurrence rate is 32%, reaching 47% after eleven years old. A significant relationship has been observed between injury recurrence and problems related to education (odds ratio: 2.95; 95% CI: 1.75-5.00), atypical parenting situation (odds ratio: 1.70; 95% CI: 1.20-2.30), and family discord (odds ratio: 1.62; 95% CI: 1.05-2.50). Household accidents are the most avoidable ones in parents'opinion. This is not the case for road-traffic accidents, given evidence of the lack of means of protection observed in bicycle injuries. CONCLUSION: In spite of methodological issues such as control of exhaustivity of data, or difficulties to maintain a long-term surveillance sytem, this project worth carrying on with regard to provided information and usefulness for prevention. Other similar community experiences should be implemented with the aim of setting up a national-wide surveillance system, based on an homogenous data collection.
A series of well accessible cationic ruthenium allenylidene complexes of the general type [(eta6-arene)(R3P)RuCl(=C=CR'2)]+ X- is described which constitute a new class of pre-catalysts for ring closing olefin metathesis reactions (RCM) and provide an unprecedented example for the involvement of metal allenylidenes in catalysis. They effect the cyclization of various functionalized dienes and enynes with good to excellent yields and show a great tolerance towards an array of functional groups. Systematic variations of their basic structural motif have provided insights into the essential parameters responsible for catalytic activity which can be enhanced further by addition of Lewis or Bronsted acids, by irradiation with UV light, or by the adequate choice of the "non-coordinating" counterion X-. The latter turned out to play a particularly important role in determining the rate and selectivity of the reaction. A similarly pronounced influence is exerted by remote substituents on the allenylidene residue which indicates that this ligand (or a ligand derived thereof) may remain attached to the metal throughout the catalytic process. X-ray crystal structures of the catalytically active allenylidene complexes 3b.PF6 and 15.OTf as well as of the chelate complex 10 required for the preparation of the latter catalyst are reported.
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In the present work, we have studied the activity in vitro of T cell hybridoma (DO11107) in which the alpha/beta TCR genes of a cytotoxic T cell clone (KB5C20) were transfected. All clones transfected expressed CD5 molecule and have an important proliferative and cytotoxic allogenic activity.
Alterations in phagocytosis have been studied in 25 patients with idiopathic nephrotic syndrome (INS). At the time of investigation all patients had normal renal function.
Adriamycin and mitomycin C were previously found to modulate the sensitivity of lymphoma cells to lysis by certain effectors of immunity and this modulation was dependent on drug concentration. In the present studies, RDM4 lymphoma cells were treated with different concentrations of the two drugs for 24 h in culture. These treatments resulted in changes in the lipid composition, membrane fluidity, cell size distribution, and permeability to 51CrO4, Trypan blue, Acridine orange and trimethylaminodiphenylhexatriene (TMA-DPH) of the cells. Changes in some of these parameters, as a function of drug concentration, resulted in dose-response curves which were bell-like shaped, hence paradoxical similarities between non-drug-treated cells and cells treated with higher drug concentrations were observed.
The influence of alterations of plasma membrane physico-chemical properties on insulin binding have been characterized in an insulin-sensitive rat hepatoma cell line adapted to grow for several generations in culture medium enriched with linoleic acid (18:2) or with 25-hydroxycholesterol. The cells took up 18:2 and 25-hydroxycholesterol added to the culture medium, without exhibiting any sign of intolerance or intoxication. These compounds respectively increased and decreased membrane fluidity at 37 degrees C. The cells demonstrated extensive changes in insulin binding parameters in response to experimental modifications of their membrane lipid composition. When determined at 4 degrees C, insulin receptors were present in the control cells at 136,000 sites/cell but this fell to 111,000 (P less than 0.05) in cells enriched in 18:2, and rose to 176,000 (P less than 0.001) in hydroxysterol-grown cells. According to a two-site model, the main effect of 18:2 was a significant increase of the number of high-affinity sites with a concomitant decrease of low-affinity sites. The hydroxysterol had the opposite effects on these parameters. The high-affinity insulin binding capacity of the hepatoma cells was affected by lipid supplementation in a similar way, whether it was determined at 4 degrees C or at 37 degrees C. Assuming a negative cooperativity model, 18:2 enhanced the degree of negative cooperativity among the sites, while 25-hydroxycholesterol reduced it. The time-course of insulin-induced receptor down-regulation was accelerated in the cells enriched in polyunsaturated fatty acids, but reduced in cells exposed to 25-hydroxycholesterol. These insulin-binding alterations cannot be directly related to modifications of cellular growth rate, receptor internalization or membrane fluidity per se, and are discussed as being more likely due to membrane lipid composition than to overall cell metabolism modifications.
We altered the cellular lipid composition of an insulin sensitive rat hepatoma cell line through supplementation of the culture medium with linoleic acid (18:2) or 25-hydroxycholesterol, and we studied the effects on insulin stimulation of aminoacid transport system A and glycogen synthesis. The basal rate of sodium-dependent aminoisobutyric acid uptake was slightly reduced in hydroxysterol-treated cells and increased in 18:2-enriched cells. Maximal insulin stimulation of transport was decreased by about 40% in both 18:2 and 25-hydroxycholesterol modified cells, as compared to control cells. In addition to reduced responsiveness, the hydroxysterol-treated cells also showed a diminished sensitivity to insulin, as revealed by a right-shift of the dose-response curve leading to a ED50 of 1.2 X 10(-8) M (P less than 0.02), as compared to 2.45 X 10(-9) M in control cells and 2.13 X 10(-9) M in 18:2 enriched cells. Concerning glycogen synthesis, the basal rate was unaffected by 25-hydroxycholesterol supplementation and slightly reduced in cells enriched in 18:2. Maximal insulin stimulation of glycogen synthesis was reduced by about 40% in both types of lipid modified cells. 25-Hydroxycholesterol again provoked a decrease in sensitivity to insulin: the ED50 was enhanced to 4.9 X 10(-9) M (P less than 0.05), as compared to 1.25 X 10(-9) M in control cells and 1.57 X 10(-9) M in 18:2-supplemented cells. Taken together with the previously reported changes of insulin binding to lipid modified hepatoma cells (Bruneau et al. (1987) Biochim. Biophys. Acta 928, 287-296) our results demonstrate an influence of alterations of the cellular lipid composition on both binding and biological actions of insulin, leading to an insulin-resistant state. Divergences between insulin binding and action were obtained and it was suggested that post-binding events may be responsible for the observed changes. Our findings may be relevant to experimental and clinical states of insulin resistance.
In IgA glomerulonephritis (GN), the pathogenic role of IgA is well documented, but the specificity of these IgA is unknown. Cases of celiac disease associated with IgA GN have been reported and led us to investigate the role of gliadin sensitivity. We measured IgA, IgG and IgM antibodies to gliadin, beta-lactoglobulin and ovalbumin by ELISA (results expressed as optical density; OD) in 27 patients with primary IgA GN, 14 with membranous GN (MGN), 21 with idiopathic nephrotic syndrome (INS) and 21 healthy controls. The normal value for antigliadin IgA was less than 0.650 OD. 19/27 patients with IgA GN had a raised level versus 2/14 in MGN and 2/21 INS (p less than 0.001: IgA GN vs. MGN, INS and controls). Antibodies to beta-lactoglobulin were rarely found and were not more frequent in IgA GN. Cross-reactivity with reticulin was investigated in 16 patients who were serum-positive for IgA antigliadin: no reticulin antibodies were detected by immunofluorescence. Antigliadin IgA are of diagnostic value for distinguishing IgA GN from other GN, with a sensitivity of 70%, a specificity of 89%, a positive predictive value of 83% and a negative one of 79%.
Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) was first used in glomerulonephritis (GN) in 1966 but its efficiency is still debated. We studied the antiproteinuric effect of such a treatment in a double-blind study. 29 GN patients with normal renal function (17 membranoproliferative GN, 12 IgA GN) were randomly assigned to receive 100 mg/day of diclofenac or placebo for at least 2 months. There was a significant antiproteinuric effect of diclofenac versus placebo with a fall of 70% in the diclofenac group versus 6% in the placebo group (p less than 0.001 with the Mann-Whitney test). The median was 3 mg/min at onset and 2.45 mg/min after 2 months treatment with the placebo. In the diclofenac group, it was 2.2 and 0.95 mg/min, respectively (p less than 0.01). Diclofenac did not significantly increase creatinine levels. Gastric irritation was noted only once. This study establishes the short-term antiproteinuric action of diclofenac. Whether this action affects the final outcome is not yet determined.
To evaluate the prevalence of food hypersensitivity in idiopathic nephrotic syndrome (INS), an oligoantigenic diet was given for 10 days to 13 patients with INS who had not steadily responded to corticosteroids; 5 of these patients were corticodependent, 3 were corticoresistant and 5 had multiple relapses. A history of allergy was present in 8 cases and an increase in total serum IgE levels in 6. Sensitivity to food antigens was documented by skin tests in 5, by the radioallergosarbent test (RAST) in 5 and by the human basophil degranulation test (HBDT) in 11. At the end of the oligoantigenic diet, proteinuria was significantly reduced in the 13 patients as compared to the initial level. It decreased by more than 50% in 9 patients and disappeared completely in 5. It seems that an oligoantigenic diet is helpful in cases of INS that do not respond to corticosteroids. This argues for a role of food hypersensitivity in this disease and suggests that avoidance of specific foods on the longer term may be of benefit. This diet must be tried in INS before the initiation of immunosuppressive therapy.
A retrospective study of 134 cases of circulating "lupus anticoagulant" (LA) observed between 1975 and 1985 in the haemostasis laboratory of Henri Mondor Hospital is reported. In 66 p. 100 of cases the circulating anticoagulant was discovered fortuitously and auto-immune diseases were associated with the inhibitor only in 25 p. 100 of cases (mainly systemic lupus erythematosus). Thrombosis (venous, arterial or both) was found in 26 p. 100 of cases when auto-immune diseases were present and in 13.5 p. 100 of cases in the absence of these diseases. Spontaneous abortion was observed in 42 p. 100 of the women when the anticoagulant occurred in the course of an auto-immune disease and in 4 p. 100 when another or no underlying disease were identified. False-positive VDRL and thrombocytopenia were found associated with LA mainly in auto immune diseases. Anticardiolipin antibodies were positive in 37 p. 100 of 32 patients without any difference between auto-immune diseases and other pathologies. These results show that the "lupus anticoagulant" is a frequent coagulation abnormality even when auto-immune diseases are absent. The differences observed between auto-immune diseases and other pathologies in respect to clinical manifestations and biological findings associated with lupus anticoagulant suggest that the so-called "lupus anticoagulant" represents a group of antibodies with probably different specificities but which act in a similar manner in "in vitro" coagulation tests.
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The in vivo function of the reticulo-endothelial system in humans is currently studied by the blood clearance of 51Cr labeled RBC sensitized with IgG anti-Rh. By replacing 51Cr by 111In we developed a method which allows imaging and assessment of clearances of circulating immune complexes (CIC) by individual organs. Nine normal subjects were studied successively with 51Cr labelled CIC and 111In-labelled CIC by blood sampling and sequential imaging. Time activity curves were obtained over spleen, liver, heart lungs and kidneys. The blood clearance values were similar with 111In (T1/2 +/- SD = 23.4 min +/- 6.4 min) and 51 Cr (T1/2 = 22.9 min +/- 5.8 min). The blood clearance derived from the time activity curve obtained over the cardiac area (T1/2 = 26.6 min +/- 8.4 min) was not significantly different from that obtained by blood sampling. Most of the CIC were taken up by the spleen with a T1/2 of 20.3 min +/- 4.1 min. Although hepatic uptake was observed in all subjects, it was lower than that of the spleen and CIC were subsequently released from the liver in five of the nine patients. The spleen/liver ratio increased with time, reaching a plateau averaging 24.0 +/- 5.8 within 80 min in all subjects. CIC imaging allows, by a non-invasive procedure, the computation of CIC blood clearance and the estimation of the respective role of spleen and liver in phagocytic function.
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