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Biomedical subjects

J Bernier

Publications and source records attributed to J Bernier.

At least 73 records · Page 4Linked to original sources
PubMed1995

Acute thrombogenicity of arterial prostheses exposed to reduced blood flow in dogs: effects of heparin, aspirin, and prostacyclin.

Thrombogenesis is considered the principal cause of early failure of arterial grafts. Although antithrombotic drugs are recommended, their efficiency under low blood flow conditions is still being debated. In this study, we evaluated the ability of three drugs to modify the thrombotic properties of blood and, consequently, to influence platelet and fibrin deposition on the luminal surface of polyester arterial prostheses. In dogs receiving saline (control, n = 10), heparin (100 U/kg, n = 5), aspirin (325 mg, n = 5), or prostacyclin (15 ng/kg/min, n = 5), a 30-cm, woven, loop-shaped, DeBakey arterial prosthesis was implanted as a substitute for the infrarenal aorta and exposed to reduced blood flow (50 ml/min) for 4 h. The parameters of the blood measured included activated clotting time (ACT) and platelet aggregation with collagen, determined before and after each treatment. Blood deposits were quantified using 111In labeled platelets and 125I-labeled fibrinogen. The ACT was significantly prolonged only after heparin treatment, and platelet aggregation, which was decreased by 35% (p < 0.05) after heparin treatment, was almost abolished after aspirin and prostacyclin treatments. As compared with the control group, both platelet and fibrin uptake on the luminal surface of the prostheses were reduced significantly by heparin by 87 and 37%, respectively. Despite their inhibition of platelet aggregation in vitro, aspirin and prostacyclin induced no significant change in platelet and fibrin deposition on the luminal surface of the woven polyester arterial prostheses under low blood flow conditions. Under such conditions, however, thrombin generation with subsequent platelet-fibrin deposition was prevented by use of heparin anticoagulant therapy.

Administration, Oral↗
PubMed1995

A simple technique for staining of cell membranes with imidazole and osmium tetroxide.

We describe a simple new technique based on the affinity of imidazole and osmium tetroxide for unsaturated lipids. Organs (e.g., kidney, liver, intestine) were perfused in vivo with a glutaraldehyde solution. Tissue fragments were then immersed in a solution containing imidazole and OsO4 and are further stained with a double lead and copper citrate solution. Ultra-thin (0.06 microns) or thick (0.1-0.3 microns) sections were observed with transmission electron microscopy (80-100 kV). The method presented permits excellent visualization of cell membranes (e.g., endoplasmic reticulum, endocytotic apparatus) because it favors good resin penetration and the alkaline pH preserves cell volume. A better stereomicroscopic analysis of the relationship between cell organelles can be carried out with thick sections. The imidazole/osmium can be used routinely because the technical steps are easy and simple to follow. Furthermore, it can complement other cytochemical methods.

Animals↗
PubMed1995

Immunotoxicity of heavy metals in relation to Great Lakes.

Heavy metals including mercury, lead, and cadmium are present throughout the ecosystem and are detectable in small amounts in the Great Lakes water and fish. The main route of exposure of humans to these metals is via the ingestion of contaminated food, especially fish. Extensive experimental investigations indicated that heavy metals alter a number of parameters of the host's immune system and lead to increased susceptibility to infections, autoimmune diseases, and allergic manifestations. The existing limited epidemiologic data and data derived from in vitro systems in which human peripheral blood leukocytes were used suggested that the human immune system may also be at increased risk following exposure to these metals. The magnitude of the risk that the presence of such metals in the Great Lakes may pose to the human immune system, and consequently to their health, is not known. In this review, the available data with respect to potential adverse effects of heavy metals on the immune system of humans and experimental animals are discussed, and additional data requirements are suggested.

Adolescent↗
PubMed1994

LFA-1-mediated antigen-independent T cell adhesion is regulated by CD4 and p56lck tyrosine kinase.

We examined the role of CD4 and p56lck in the regulation of LFA-1-dependent T cell adhesion to B cells and to fibroblasts expressing ICAM-1 and HLA-DR by using various transfectant constructions. Although CD4 transfection in CD4low HUT78 T cell lines did not significantly modify their maximal binding to B cells and fibroblasts, it made the LFA-1-dependent adhesion sensitive to inhibition by anti-CD4 Ab, HIV-1 (env) gp 160, and a 12-mer peptide encompassing the 35-46 sequence of the beta 1 domain of the MHC class II molecule. CD4low HUT78 T cell adhesion to B cells was stable over 60 min, whereas expression of CD4 led to a transient adhesion. In addition, adhesion of CD4+ T cells to MHC class II- B cells was also stable. The CD4-dependent alteration of adhesion required the association of CD4 with p56lck because expression of mutant forms of CD4 unable to bind p56lck resulted in a lack of CD4-dependent regulation of adhesion. Herbimycin A, an inhibitor of tyrosine kinase activity, reversed the effect of CD4 transfection on adhesion. These results indicate that ligand binding to CD4 delivers a signal-inducing cell dissociation by activating p56lck tyrosine kinase. This regulatory pathway may provide a quick and reliable way for multiple and subsequent Ag-independent adhesion events of CD4+ T cells.

Adult↗
PubMed1994

Accelerated radiotherapy in glioblastoma multiforme: a dose searching prospective study.

The EORTC Radiotherapy Cooperative Group performed a prospective phase II study in glioblastoma multiforme using accelerated radiotherapy in escalating doses. The aims of the study were to investigate acute and late toxicity as well as tumor response and survival. Only the CT-enhanced tumor zone plus a margin of 2-3 cm were treated (mean volume, 1034 +/- 477 cm3). Radiotherapy was administered with 5-18 MV photons. The radiation schedule consisted of 3 fractions of 2 Gy/day, separated with at least 4 h. The first group of patients was scheduled to receive a total dose of 42 Gy, 21 fractions in 9 days. The total dose was then escalated up to 48 Gy (24 fractions in 10 days), 54 Gy (27 fractions in 11 days) and 60 Gy (30 fractions in 12 days). The numbers of patients entered in each dose-level group were 15, 17, 18 and 16, respectively. Acute toxicity was mild, nausea/vomiting was absent in 91% of the patients. In 80% of the patients the neurological condition improved or remained stable compared with the start of radiotherapy but in 58% of the patients steroids were necessary, either increased in dose or initiated. Acute toxicity did not increase with increasing radiation doses although patients treated with 60 Gy more often required steroids than the other groups. Late toxicity was strongly suspected in 2 patients receiving 52 Gy and 56 Gy, respectively. Within the whole group of 66 patients only one recurrence outside the primary site was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Neoplasms↗
PubMed1993

Prognosis of human chorionic gonadotropin-producing seminoma treated by postoperative radiotherapy.

PURPOSE: To clarify the controversy about the management and prognosis of human chorionic gonadotropin-producing seminoma, the records of 132 patients with abnormal human chorionic gonadotropin values treated with radiotherapy were analyzed. METHODS AND MATERIALS: The records of 1169 patients with pure seminoma treated in 10 institutions were screened for serum or urinary human chorionic gonadotropin. One hundred and thirty two patients with elevated human chorionic gonadotropin were found: 96 Stage I, 20 IIA, 7 IIB, 8 III and 1 IV. Median age was 34 y., mean follow-up was 5.0 years [range 1-12 y]. All received infradiaphragmatic radiotherapy (median dose 30 Gy), 25 (2 Stage I, 11 IIA, 5 IIB and 7 III) supradiaphragmatic radiotherapy (median dose: 28.5 Gy) and 10 had also initial chemotherapy (3 Stage IIB 6 III and 1 IV). Patients were allocated to three groups according to human chorionic gonadotropin values: (a) moderate elevation: up to 10 times (104 pts), (b) high elevation: 10 to 100 times (20 pts), (c) very high elevation: over 100 times the upper limit of normal value (8 pts). RESULTS: The proportion of Stage I, II and III was 76%, 19%, 5% in the ME group versus 50%, 35%, 15% in the high elevation group (p < 0.05). In the very high elevation group there were 7 Stage I and 1 Stage IV. Of 132 patients, six died (three dead of disease, two suicides, one acquired immunodeficiency syndrome). The 5 years overall survival probability was 94%. There were seven recurrences (initial stage: 1 Stage I, 2 IIB, 3 III and 1 IV). Of these, there were one in-field recurrence, 3 out of field and 3 in both sites. In 5 of 7, the human chorionic gonadotrophin level was again elevated at recurrence. The 5 years recurrence-free-survival probability was 94% (98% for Stage I, 100% for Stage IIA and 65% for Stage IIB and III [p < 0.001 between I and IIB + III, p < 0.05 between IIA and IIB + III]). Four of the 7 recurrences were salvaged by chimiotherapy +/- radiotherapy. In the high elevation and very high elevation groups, the 5 years recurrence-free-survival was 88%, vs. 96% for the moderate elevation group (p = 0.10). CONCLUSION: Based on this series of patients, human chorionic gonadotropin production is not an unfavorable prognostic factor in pure seminoma. Even in the subgroups with high or very high human chorionic gonadotropin levels (who had a higher proportion of advanced stages), the prognosis remained excellent. In Stage I and IIA seminoma with abnormal human chorionic gonadotropin levels, recurrence rate after post-operative radiotherapy alone is extremely low.

Adolescent↗
PubMed1993

The programme of quality assurance of the EORTC radiotherapy group. A historical overview.

A quality assurance programme was activated in 1982 in the EORTC Cooperative Group of Radiotherapy. Definitions and contents of quality assurance and quality control, definitions of errors and deviations (systematic, occasional) are given. The methodology and steps of the quality assurance programme adopted over the past ten years are briefly described. The need for an interaction between national and international networks is emphasized. Consensus statements on quality assurance in radiotherapy provided during the January 1993 Geneva meeting conclude this introduction to the detailed reports on the quality assurance programme of the EORTC Cooperative Group of Radiotherapy.

Europe↗
PubMed1993

Mailed TL dosimetry programme for machine output check and clinical application in the EORTC radiotherapy group.

The Radiotherapy group of the European Organisation for Research and Treatment of Cancer (EORTC-RT) has been performing quality assurance with mailed TL dosimetry since 1986. The programme consists of therapy machine output checks, in vivo measurements, and dosimetry for brachytherapy. The therapy machine output checks have revealed a few large deviations (greater than 7%) between EORTC-measured and institute-stated dose, but also shown an improvement in the dosimetry of the participating institutes as a result of consecutive mailings. The use of in vivo dosimetry with mailed TLD has proven that it is feasible to detect deviations of +/- 5%. The results have shown deviations within +/- 5% for dosimeters located well within the radiation field for internal measurements in the pelvic region. Dosimetry of brachytherapy has been performed for low dose rate 192Ir sources. Differences of 14% can be seen between the participating centres.

Brachytherapy↗
PubMed1993

Is reseeding from the primary a plausible cause of node failure?

In a previous analysis of node failures in 1251 consecutive patients with node positive oropharyngeal and pharyngolaryngeal squamous cell carcinomas treated by external radiotherapy alone at the Institut Curie, the main reasons for patient exclusion were node recurrence associated with primary failure (N+T failures) and doses less than 55 Gy. These exclusions reduced the number of node failures from 399/1251 (32%) to 77/798 (10%). Multivariate analysis of node recurrence indicated that node size and fixity, treatment duration, and T stage of primary were significant (higher probability of isolated node failure for the T1-T2 primaries). In the present analysis, it is noted that 60% of the N+T failures were observed less than 1 month after the completion of the irradiation and, therefore, were not likely the result of reseeding from the primary tumor. When all 1251 patients were included in the analysis, the probability of nodal failure increased for larger nodes, T4 primaries, lower nodal doses, presence of contralateral node metastases, and nodal fixation to the surrounding structures. No influence of the primary site was found. Treatment duration was closely associated with total dose to the nodes. The best description of the data was obtained with a model including total dose and not treatment time. However, as in the previous analysis, the exclusion of low-dose (less than 55 Gy) treatments resulted in the loss of a significant dose-control relationship. We conclude that the majority of node failures is unlikely to result from reseeding from the primary tumor, and therefore should not be excluded from local-control analyses. From a more radiobiological point of view, the exclusion of palliative treatments is questionable when studying the effect of dose on local control.

Adult↗
PubMed1993

Risk factors of corneal graft failure.

PURPOSE: To measure the association between potential risk factors and corneal graft failure. Two failure outcomes are compared: those with and those without a prior immune allograft reaction. METHODS: Based on a single-center observational study design, 539 adult recipients of a corneal graft were followed for a median time of 30 months. Survival analysis was carried out. RESULTS: Eighty-two graft failures were recorded. Of 82 failures, 53 (65%) were not preceded by an immune allograft reaction. Presence of blood vessels in the recipient cornea was associated with a twofold increase in risk for both failure outcomes. Three factors increased the risk of failure without an immune reaction: prior glaucoma or uveitis (adjusted relative risk estimate = 3.1), vitreous surgery with the graft (adjusted relative risk estimate = 2.0), and a repeat graft in the study eye (adjusted relative risk estimate = 2.0). Conversely, large graft wound size (adjusted relative risk estimate = 2.0). Conversely, large graft wound size (adjusted relative risk estimate = 2.9) and human leukocyte antigen (HLA)-A, -B incompatibility (adjusted relative risk estimate = 2.2) were associated with failures that followed an immune reaction. CONCLUSION: In this study, the authors support the clinical impression that corneal graft failures with and without a prior immune reaction are distinct phenomena. Enhanced surveillance in recipients with glaucoma and early intensive treatment of allograft reactions are recommended to improve the outcome of corneal grafts.

Cataract Extraction↗
PubMed1993

Diagnostica--a Bayesian decision-aid system--applied to hypertension diagnosis.

"Diagnostica" is a Bayesian statistical tool designed to collect and store the patient's data, suggest a diagnosis, and explain the decision in terms of density distributions. The program is written in C language on MacIntosh support. It is described using the case study of differential diagnosis between essential and secondary hypertensions (i.e., fibrodysplastic renal artery stenosis, atheromatous renal artery stenosis, Conn's syndrome, nephropathy and pheochromocytoma). Seventeen experimental parameters were taken into consideration, all of them available during the first medical examination. The density distributions of all items were established from the ARTEMIS experimental database. Both a priori probabilities of different types of hypertension and loss coefficients are taken into account in the calculations. Diagnostica can be used in a "make diagnosis" mode or in an "edition" mode. In the first case it can serve a physician in everyday practice; in the second it becomes a tool for medical research.

Bayes Theorem↗
PubMed1992

Crosslinking CD4 by human immunodeficiency virus gp120 primes T cells for activation-induced apoptosis.

During human immunodeficiency virus (HIV) infection there is a profound and selective decrease in the CD4+ population of T lymphocytes. The mechanism of this depletion is not understood, as only a small fraction of all CD4+ cells appear to be productively infected with HIV-1 in seropositive individuals. In the present study, crosslinking of bound gp120 on human CD4+ T cells followed by signaling through the T cell receptor for antigen was found to result in activation-dependent cell death by a form of cell suicide termed apoptosis, or programmed cell death. The data indicate that even picomolar concentrations of gp120 prime T cells for activation-induced cell death, suggesting a mechanism for CD4+ T cell depletion in acquired immune deficiency syndrome (AIDS), particularly in the face of concurrent infection and antigenic challenge with other organisms. These results also provide an explanation for the enhancement of infection by certain antibodies against HIV, and for the paradox that HIV appears to cause AIDS after the onset of antiviral immunity.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Combined effects of selected insecticides on humoral immune response in mice.

Biological effects data with single insecticides are far more abundant than with mixtures. These data cannot be used directly to predict the effects of insecticide mixtures. Three insecticides of different chemical classes: organochlorine; dieldrin, organophosphate; malathion, and carbamate; carbofuran, previously evaluated for their immunotoxic potential, were selected for studies of combined acute exposure in C57B1/6 inbred mice. The humoral response to sheep red blood cells (SRBC) and the functional activities of peritoneal macrophages, such as phagocytosis of fluorescent beads and presentation of a single protein antigen, avidin, were examined after in vivo exposure of mice to different combinations of the selected pesticides and compared with the vehicle controls. Regarding exposure to single substances, the data confirmed the immunosuppressive potential of dieldrin and carbofuran and the immunopotentiating effect of malathion. Following the acute concomitant exposure to dieldrin/carbofuran mixture, however, values for the parameters of antigen presentation, primary IgM antibody response to SRBC antigen, and macrophage phagocytosis, returned to control or above-control values, indicating a lack of any synergistic or additive effects of the chemicals on the immune response. Thus, it was concluded the dieldrin/carbofuran mixture had an antagonistic effect on the humoral response to SRBC and the macrophage phagocytic activity, in comparison with the action of administration of each of the insecticides alone.

Animals↗
PubMed1991

Evaluation of the immunomodulatory potential of diethyl dithiocarbamate derivatives.

The cytotoxicity, immunotoxicity and immunomodulatory potential of four dithiocarbamate derivatives were assessed and compared with the effects of Immuthiol (diethyl dithiocarbamate, DE-DTC) in mice. Cellular stimulation and cell viability were examined after in vitro exposure of spleen lymphocytes to selected DTC analogues: N-methyl-D-glucamine dithiocarbamate (NMG-DTC), dimethyl dithiocarbamate (DM-DTC), dibuthyl dithiocarbamate (DB-DTC) and diisobuthyl dithiocarbamate (DIB-DTC). Lymphocyte activation by plant and bacterial mitogens: concanavalin A (Con A), phytohaemagglutinin (PHA), lipopolysaccharide (LPS) and allogeneic stimulation of cells in mixed lymphocyte reaction (MLR) were examined in vitro in the presence of 10(-4)-10(-9) g/ml DE-DTC and other selected DTC derivatives. No direct in vitro lymphoproliferative activity of DTC derivatives was observed, although a relatively stronger cytotoxicity with DE-DTC and DM-DTC was noted. In addition, the in vivo effects of DTC derivatives were examined by cytofluorometric profile of splenic and bone marrow cells as well as in mitogenic and allogenic responses, after i.v. exposures of animals to two subsequent (25 mg/kg b.w.) doses of the chemical. Less cytotoxic DIB-DTC, NMG-DTC and DB-DTC expressed weak in vivo immunostimulatory potential when compared with the effect of DE-DTC, whereas the effects of DM-DTC on alloantigenic and mitogenic lymphocyte stimulation were comparable with the known effects of DE-DTC. Cytofluorometric studies showed that the number of cytotoxic/suppressor T-cells (Ts) and helper T-cells (Th) in the cell was increased by DE-DTC and NMG-DTC only. In addition, DM-DTC appeared to affect the Ts/Th ratio. DE-DTC did not affect the B-cell subpopulation, whereas other derivatives induced marked modifications of the pre-B-cell subpopulations in bone marrow. Our data suggest that in vivo the immunostimulatory effect of DM-DTC could be accompanied with major changes in bone marrow B-cell frequency and alteration of spleen Ts/Th ratio.

Adjuvants, Immunologic↗
PubMed1991

Bayesian statistics as applied to hypertension diagnosis.

This paper deals with the following hypertension diagnoses: essential hypertension and five types of secondary hypertension: fibrodysplasic renal artery stenosis, atheromatous renal artery stenosis, Conn's syndrome, renal cystic disease, and pheochromocytoma. Only blood pressures, general information and general biochemical data are taken into account. Nineteen items were finally selected, by statistical investigation of experimental data, as being both discriminative and independent. The marginal density distributions of every item, and then joint density distribution functions were determined within six types of hypertension. The frequency of a given hypertension type within the hypertensive patients was used as prior probability of this state. The loss matrix was established by medical arguments. The expected loss corresponding to six possible decisions could thus be calculated for all cases. Both the ratio of secondary hypertensions that could be inferred from our set of data (not including the results of complementary tests) and that of correct "essential" hypertension diagnosis proved to be satisfactory.

Bayes Theorem↗