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Biomedical subjects

G Bernard

Publications and source records attributed to G Bernard.

At least 37 records · Page 2Linked to original sources

[Mechanical and metabolic complications of hysteroscopic surgery: report of a retrospective study of 352 procedures].

Our objective was to determine, in a retrospective study of 352 operative hysteroscopies: (a) the rates and the types of complications and (b) the risk factors of peroperative perforations. The most important complications represented 1.7% including two haemorrhage, one symptomatic metabolic abnormalities and three uterine perforations with bowel injuries (0.8%). Furthermore, minor complications were observed in 9.3% including non symptomatic metabolic abnormalities (5.5%) and uterine perforations without visceral injury. Among mechanical complications, the majority were uterine perforations (4%). No relation was found between menopausal status of the patients and the occurrence of uterine perforation. In contrast, the perforation rate was statistically greater in patients treated for synechia than those found for myoma (p < 0.0001). Furthermore, the perforation rate was statistically higher for resection of myomas as compared with endometrial resection (p < 0.0001) or polyp resection (p < 0.0008). Moreover, in our experience, the perforation rate depended on hysteroscopic experience of surgical operators.

Adult↗

[Laparoscopy-assisted hysterectomy and laparoscopic preparation. Apropos of a series of 177 cases].

Our objective was to determine the limits of laparoscopic-assisted vaginal hysterectomy (LAVH) and the value of a preoperative scoring system to determine the operative approach to hysterectomy. Between January 1991 and December 1996, 152 out of 177 patients had LAVH and 25 had laparoconversion. The mean operating time was 163 min. The overall postoperative complication rate was 8.4%. The hospital stay was 4.8 days for LAVH versus 6.2 days for laparoconversion (p < 0.01). For each patient, a preoperative scoring system was established according to uterine size, previous laparotomy, uterine mobility, pelvic adhesions and endometriosis stage. The laparoconversion rate increased according to the score, as it was 7.8% for a score < or = 7 and 80% for a score > 7. LAVH offers a technique to convert some abdominal hysterectomies into vaginal hysterectomies. The use of the preoperative scoring system may help to determine patients who may benefit from the laparoscopic route and those with a high risk of laparoconversion.

Adult↗

Apoptosis of immature thymocytes mediated by E2/CD99.

E2/CD99 is a 32-kDa transmembrane molecule that does not belong to any known family of proteins. It appears to regulate adhesion properties of T cells as previously reported, in particular, the induction of homotypic adhesion in CD4+ CD8+ thymocytes. Apoptosis induced via E2/CD99 displays characteristic morphologic features, but includes early mitochondrial alterations and phosphatidylserine exposure at the outer leaflet of the plasma membrane. It is not followed by detectable DNA fragmentation, and its time course is much longer than apoptosis induced via the Fas/CD95 pathway. It requires 18 h for completion. E2/CD99-induced apoptosis does not require any RNA or protein synthesis and still occurs following blockage of the Fas pathway. It is, however, dependent on CPP32 and IL-1beta-converting enzyme-type cysteine proteases, as shown by blockade with their respective specific inhibitors. This effect is restricted to double-positive thymocytes carrying an intermediate density of CD3 and including all CD69+ cells. Thus, E2/CD99 apears to mediate a distinctive apoptotic signal at a critical stage of thymocyte differentiation, i.e., when positive selection is known to occur.

12E7 Antigen↗

Integrin-associated protein (CD47) is a comitogenic molecule on CD3-activated human T cells.

IAP is a glycoprotein functionally and physically associated with some integrins, i.e., the leukocyte response integrin and the beta3 integrin chain on placenta, platelets, and polymorphonuclear cells. IAP may act as a transducer element in activation mediated via these integrins. Since IAP is present at high density on peripheral T lymphocytes we have investigated its involvement in T cell activation. We tested three mAbs against IAP, namely B6H12, BRIC126, and 2D3, which recognize two distinct epitopes. IAP cross-linking with B6H12 or BRIC126, but not 2D3, transduces costimulatory signals within highly purified CD3-activated T lymphocytes, i.e., enhancement of proliferation, CD25 expression, and IL-2 secretion, while no effect was observed upon CD2 stimulation. However, we could not observe any functional association between IAP and integrins on peripheral T cells. In an attempt to explore further the activation signal delivered by IAP, we show here that IAP cross-linking with the comitogenic B6H12 mAb induces the phosphorylation on tyrosine of several proteins, one of which is identified as p56(lck) protein tyrosine kinase. Moreover, we observed that IAP is associated with p56(lck) on PMA-activated, but not on resting, T cells. These data suggest that on T cells, IAP may be involved directly via a specific ligand in cell-matrix or cell-cell interactions. Such interactions could trigger protein tyrosine phosphorylation pathways, which play an important role in both maturation and activation of T cells.

Antibodies, Monoclonal↗

How to use articles about harm: the relationship between high tidal volumes, ventilating pressures, and ventilator-induced lung injury.

BACKGROUND: Intensivists commonly encounter patients who may be inadvertently harmed by critical care interventions. This article is designed to guide clinicians in the evaluations of an individual article assessing a question of harm, as well as the sum of multiple pieces of evidence. OBJECTIVES: To assess the vaidity of a group of articles about the relationship between high tidal volumes and ventilating pressures on ventilator-induced lung injury; to interpret the results of these studies; and to consider whether they apply in practice. DATA SOURCES: Issues of harm are sometimes measured in randomized trials, but are evaluated more often in myriad observational studies. DATA EXTRACTION: We use critical appraisal guides for experimental studies (e.g., randomized trials) and observational studies (e.g., cohort studies, case-control studies and case series) that evaluate the potentially harmful exposure of high tidal volumes and ventilating pressures. This involves assessing the validity of the research, then determining the strength of association between the putative harmful exposure and adverse outcomes. These study designs and their interpretation using relative risks and odds ratios are reviewed. Finally, the relevance of this information (or lack thereof) to clinical practice needs to be determined. DATA SYNTHESIS: Examining these studies individually and in totality, there appears to be a relationship between high tidal volumes and ventilating pressures, although the strength of inference from this research is limited by design issues and sample sizes. CONCLUSIONS: Critically appraising a body of literature is more challenging than evaluating a single study, but often gives a broader view of the available evidence. Future large, rigorous, randomized trials of different approaches to mechanical ventilation will help to advance our understanding and to better inform our practice.

Clinical Trials as Topic↗

The efficacy and acceptability of amineptine versus fluoxetine in major depression.

The temporal dimension, particularly anticipation, appears to be a very important component in the understanding of depressed patients. In a 90-day multicentre study, the efficacy and acceptability of amineptine and fluoxetine were compared in 169 patients with major depression. Comparison of the two antidepressants was based on double-blind methods, after random allocation of the treatments between two parallel groups. The two drugs did not differ over the whole course of the study, but the improvement in scores on day 4 was globally more marked in the amineptine than the fluoxetine group. Intragroup analysis showed that amineptine was significantly superior to fluoxetine on the retardation pole of the mood, anxiety, retardation, danger scale. The positive effect of amineptine on anticipation may enable the depressed patient to make plans for the future. Anticipation may be a key dimension to be more precisely explored in specific psychopharmacological protocols with antidepressants.

Adolescent↗

Role of the type I interferons in allograft rejection.

Type I interferons are potent immuno-modulatory cytokines that enhance expression of the major histocompatibility complex (MHC) class I antigens, T-cell cytotoxicity, and natural killer (NK) cell activity, all of which are implicated in graft rejection. A monoclonal antibody (mAb) directed against the extracellular domain of the human interferon gamma (IFN-gamma) receptor (IFN-alpha R), which inhibits both the binding and biological activity of all the type I IFNs tested, exerted a dose-dependent inhibition of the mixed lymphocyte reaction and induced permanent survival of skin allografts in MHC-divergent Cynomologus monkeys treated with a subeffective dose of cyclosporin A. Marked differences were observed in the composition of T lymphocyte subpopulations in anti-IFN-alpha R mAb-treated animals relative to the various control groups. Skin biopsies from animals treated with anti-IFN-R Mab + cyclosporin A revealed very low levels of MHC class I and class II antigen expression and the absence of histological signs of rejection, whereas skin biopsies from control animals exhibited high levels of MHC antigen expression and the histological signs of acute rejection, including a pronounced lymphocytic infiltrate, edema, and necrosis. No monkey antibodies (IgG) to the mouse anti-human IFN-alpha R mAb were detected in the serum of any of the animals treated with the anti-IFN-alpha R mAb either alone or together with cyclosporin A. Treatment of lethally irradiated Cynomologus monkeys with the anti-IFN-alpha R mAb together with a subeffective dose of cyclosporin A was also found to markedly enhance the survival of animals grafted with allogeneic bone marrow cells from donors differing in both MHC class I and class II antigens. These results show that selective and lasting immunosuppression can be obtained by the short-term administration of an IFN-alpha antagonist together with a subeffective dose of cyclosporin A, and may have important implications for the therapy of human allograft rejection.

Animals↗

Comitogenic effects of very late activation antigens on CD3-stimulated human thymocytes. Involvement of various tyrosine kinase pathways.

Thymocytes display several integrins that are involved in cell-extracellular matrix interactions and differentiation processes. We have examined the role of very late activation Ag (VLA) on human thymocyte stimulation. VLA-4, VLA-5, and VLA-6 activated with either mAbs or their natural ligands (fibronectin, laminin, and vascular cell adhesion molecule-1) are able to transduce costimulatory signals in thymocytes activated via the CD3 pathway, i.e., enhancement of thymocyte proliferation, CD25 and CD69 expression, and IL-2 secretion. In contrast, activation of thymocytes with a mitogenic pair of CD2 mAb was not modified by VLA molecules. Cross-linking of both beta 1- and alpha 5-chains induced tyrosine phosphorylation of several proteins, whereas the cross-linking of the alpha 4- and alpha 6-chains did not. Moreover, a different pattern of tyrosine phosphorylation was observed when thymocytes were activated via either beta 1- or alpha 5-chains. These results suggest that VLA molecules activate tyrosine kinase pathways in thymocytes, and that different pathways would be implicated during thymocyte interactions with extracellular matrix or accessory cells, which are likely to play a role in thymocyte differentiation.

Antibodies, Monoclonal↗

The E2 molecule (CD99) specifically triggers homotypic aggregation of CD4+ CD8+ thymocytes.

We have previously described E2 as a 32-kDa transmembrane glycoprotein displaying an isomorphism, as two epitopes (defined by mAbs O662 and L129) are widely distributed on T cells whereas two epitopes are restricted to T cell subsets (defined by mAbs D44 and 12E7). E2, the MIC-2 gene product, is involved in T cell adhesion because anti-E2 mAbs against pan T epitopes block spontaneous T cell rosettes. Pan T E2 mAbs are also able to induce exposure of the phosphatidylserine at the thymocyte surface but not at the surface of mature T lymphocytes, an event most likely linked to adhesion phenomena. We now show here that the anti-E2 mAbs (0662 and L129) that block rosettes and induce phosphatidylserine exposure at the thymocyte surface, and not those reacting with epitopes not involved in adhesion, also trigger aggregation of certain immature T cell lines and no other cell lines tested. Among the normal cells tested, anti-E2 mAbs exclusively induce homotypic aggregation of CD4+ CD8+ human thymocytes. This phenomenon is temperature, energy, and Mg++ dependent, and requires an intact cytoskeleton. These adhesion properties are rather characteristic of integrins. Nevertheless, mAb against beta 1, beta 2, and beta 3 integrin chains, as well as those against alpha-chains known to be present on thymocytes, are unable to block corticothymocyte aggregation. We conclude that E2 triggers on corticothymocytes and no other T cells a homotypic adhesion pathway most likely mediated by an uncharacterized integrin.

12E7 Antigen↗

Sphingosine, oleylamine and stearylamine inhibit both CD11a/CD18-dependent and -independent homotypic aggregation: demonstration by cytofluorimetry.

An CD11a/CD18-dependent homotypic aggregation pathway is induced by triggering CD45 molecules on human thymocytes. By contrast, a CD11a/CD18-independent homotypic aggregation process is induced by triggering the CD99 molecule (E2, MIC2 gene product) expressed at the surface of either Jurkat T cells or human thymocytes. A new quantitative method based on FACS analysis of aggregated cells was used and allowed to show that both types of aggregation (CD11a/CD18-dependent and CD11a/CD18-independent) were inhibited with sphingosine, oleylamine or stearylamine. These three compounds had no effect on the expression of CD99, CD45, CD11a, CD18 or other [correction of others] known integrins expressed at the surface of the cells studied.

12E7 Antigen↗

Detection of potato leafroll virus in single aphids by the reverse transcription polymerase chain reaction and its potential epidemiological application.

A reverse transcription and polymerase chain reaction (RT-PCR) system was developed using two 20-mer primers located in the potato leafroll virus (PLRV) capsid gene. A 336-bp PCR product was detected from aphids (Myzus persicae) which had been fed on PLRV-infected plants. The PCR band was specific to PLRV as determined by Southern blots and detection by a PLRV-specific probe. As little as 5 min exposure of aphids to PLRV-infected leaves resulted in the presence of PLRV-specific bands in 13% of aphids. However, the percentage of PLRV-positive aphids increased with longer exposure to infected sources and reached 90% after 3-4 days of feeding. PLRV can be detected from a single viruliferous aphid or a single viruliferous aphid combined with up to 29 non-viruliferous aphids. PLRV can be detected from freshly collected aphids, those stored at -70 degrees C, or those stored in 70% ethanol at room temperature for extended periods. This method is applicable to assess the viruliferous nature of aphids caught in yellow-pan traps during the growing season or stored for over a year.

Animals↗

A controlled study of cognitive behaviour therapy with buspirone or placebo in panic disorder with agoraphobia.

BACKGROUND: This multicentre study compared a 16-week buspirone treatment with placebo in patients presenting with panic disorder with agoraphobia and also receiving cognitive behaviour therapy (CBT). METHOD: Double-blind testing was maintained until week 68, but not tested; 91 patients were included; 14 placebo-responders excluded; 77 patients randomised; 48 reached week 16 and 41 reached week 68. RESULTS: At week 16, within-group analysis showed significant improvements in agoraphobia, panic attacks, and depression in both groups. Generalised anxiety improved only in CBT+buspirone. Between-group comparisons showed buspirone to have an effect on generalised anxiety and agoraphobia. Changes in degree of agoraphobia and depression were correlated in subjects on CBT+buspirone only. A significantly higher proportion of women, and of subjects showing high avoidance dropped out. Positive expectations regarding medication predicted success in both groups. At week 68, improvement was retained without significant buspirone effect. CONCLUSION: Buspirone enhanced the effects of cognitive behaviour therapy on generalised anxiety and agoraphobia in the short term.

Adolescent↗

[Mid-term failure of balloon dilatation treatment of antral stenosis induced by caustics].

We report the case of an antral stricture following lye ingestion. The patient was treated by 3 dilations using a through-the-scope balloon dilator, initially with good results. One year later, the recurrence of the symptoms led to 2 other sessions of dilation without success and a partial gastrectomy was performed. The intensity of the gastric wall fibrosis on the surgical specimen, probably responsible for major motor impairment, accounts for the discordance between the good endoscopic result and the clinical failure. Endoscopic dilation of lye-induced gastric strictures could be a temporary alternative to surgical resection because the gastric wall fibrosis blemishes the long-term functional result.

Burns, Chemical↗

Engagement of the CD45 molecule induces homotypic adhesion of human thymocytes through a LFA-1/ICAM-3-dependent pathway.

Cell-cell interactions play a central role during differentiation and development of the immune system. T or B lymphocyte homotypic adhesions can be induced via several surface molecules which, in some cases, are known to trigger the LFA-1/ICAM-1 adhesion pathway. We show here that mAbs reacting with the CD45 common epitopes or restricted RO epitope lead to a strong and rapid aggregation of all human thymocytes, and of T cell lines with an immature phenotype, but not of peripheral T lymphocytes. Aggregation requires energy, a physiologic temperature, Mg2+ divalent cations, and an intact cytoskeleton. It is LFA-1 dependent because CD11a and CD18 mAbs inhibit homotypic aggregation, whereas CD11b and CD11c mAbs do not. Homotypic thymocyte adhesion, however, is not decreased by CD54 mAb (anti-ICAM-1) but is inhibited by CDw50 mAb (anti-ICAM-3). Soluble CD22 fails to induce thymocyte adhesion, suggesting that CD45-induced aggregation is triggered by another ligand. Finally, because inhibitions observed with mAbs against LFA-1 and ICAM-3 are only partial, it can be assumed that another adhesion pathway is involved in thymocyte adhesion. The adhesion event specific for thymocytes we describe here is likely to play an important role in T cell differentiation.

Antibodies, Monoclonal↗

Developmental effects of intrauterine growth retardation on cerebral amino acid transport.

Early restriction of nutrients during the perinatal period of life can modify the development of the mammalian fetus and have marked repercussions on the ontogeny of the CNS. The brain is vulnerable to undernutrition, with delayed morphologic and biochemical maturation leading to impaired functions. The aim of the present investigation was to assess whether modified brain neurotransmitter and amino acid concentrations found in an animal model of intrauterine growth retardation were related to modified blood-brain amino acid transport properties. Four amino acids were tested: alanine and taurine, plus two neurotransmitter precursors, tryptophan and tyrosine. Intrauterine growth retardation was induced by restriction of maternal-fetal blood flow from the 17th d of gestation. Blood-brain transport of these amino acids was measured by i.v. injection of radiolabeled amino acids in 7-d-old, 21-d-old, and 60-d-old intrauterine growth-retarded or control rats. No major statistical differences were revealed either for brain regional transport or between intrauterine growth-retarded animals and controls at any age studied. Transfer coefficients and influxes remained statistically similar for almost all brain regions in both groups. A significant decrease and different time course for amino acid transport with age related to the blood-brain barrier maturation are confirmed in this model. Our results are related to a major role of the blood-brain barrier as a part of mechanisms leading to "brain growth sparing."

Age Factors↗

Monoclonal antibodies directed against the E2 protein (MIC2 gene product) induce exposure of phosphatidylserine at the thymocyte cell surface.

Monoclonal antibodies (mAbs) directed against E2, a 32-kDa transmembrane protein encoded by the MIC2 gene located in the pseudoautosomal region, induce a transbilayer movement of phosphatidylserine and, to a lesser extent, phosphatidylethanolamine in human thymocytes and a Jurkat T lymphocytes. The translocation of phosphatidylserine has been evidenced by using either derivatization of anionic phospholipids with trinitrobenzenesulfonate (TNBS) or cytofluorimetry after labeling of cells with antiphosphatidylserine antibodies. The perturbation of membrane phospholipids induced by anti-E2 mAbs was further evidenced by labeling the cells with merocyanine 540. The specificity of anti-E2-induced perturbations of membrane asymmetry was tested by using a number of mAbs able to activate T cells, including CD3 and CD2. The results strongly suggest that anti-E2-induced changes in PtdSer are related to cell aggregation since the same mAbs specifically induce the aggregation of both thymocytes and Jurkat cells and since the E2 molecule has been previously implicated in the adhesive properties of human T cells with erythrocytes.

12E7 Antigen↗

Hormonal influence on the permeability of the blood-brain barrier: effect of an analog of adrenocorticotropic hormone, beta 1-24 corticotrophin.

Regional unidirectional transport of alpha-aminoisobutyric acid (AIB) (mol. wt.: 104) and sucrose (mol wt.: 342) which have a low permeability across the intact endothelium was investigated in brain of rats either treated with synacthène: an analog of ACTH, tetracosactide retard (beta-1-24 corticotrophin) or in brain of placebo-treated controls. Three days treatment with synacthène, reduced the rate of influx of AIB and sucrose in most of the brain regions studied especially in thalamus, hypothalamus, cortex, and caudate nucleus without affecting the vascular compartment. The brainstem, cerebellum and white matter were less affected. These experimental findings may suggest that ACTH exhibits significant influence on hormonal regulation of blood-brain barrier permeability. Thereby such a regulation may involve the entry of polar compounds into the CNS and may influence the central effects of diffusion-limited drugs.

Aminoisobutyric Acids↗