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Biomedical subjects

C Brunet

Publications and source records attributed to C Brunet.

At least 37 records · Page 2Linked to original sources
PubMed1997

Simultaneous bilateral oophorectomy does not improve prognosis of postmenopausal women undergoing colorectal resection for cancer.

PURPOSE: Synchronous or metachronous ovarian metastases are common along the natural course of colorectal carcinoma. We attempted to prospectively assess the prognostic impact of simultaneous bilateral oophorectomy in postmenopausal women undergoing curative resection for colorectal cancer. METHODS: Between 1980 and 1990, simultaneous bilateral oophorectomy was proposed in each postmenopausal woman referred to our institution for treatment of colorectal cancer. A subset of 92 patients underwent a curative resection. Therefore, two groups were designed for comparison of the procedure. Group I included 41 patients who accepted surgical castration, and Group II consisted of the 51 remaining patients who refused. Prospective analysis of all patients was performed. Results were assessed with a follow-up of 60 months after surgery, with 97.9 percent completion. Local recurrence and liver metastases rates were compared by the chi-squared test. Survival in each group was calculated by the Kaplan-Meier method and compared by the log-rank test. RESULTS: One patient (1/41; 2.4 percent) had ovarian metastases detected on the operative specimen. Local recurrence or liver metastases rates were not affected by oophorectomy (P = 0.73; P = 0.25). Five-year actuarial survival rates were not significantly different whether patients had oophorectomy (81.6 percent) or not (87.9 percent; P = 0.62). CONCLUSIONS: Our results suggest that microscopic synchronous ovarian metastasis is rare at the time of curative resection of a colorectal carcinoma in postmenopausal women. Because simultaneous bilateral oophorectomy does not modify prognosis, this procedure seems to be unwarranted.

Adenocarcinoma↗
PubMed1997

[Demonstration of a cranial autopsy performed during the Great Plague of Marseille (1720-1722)].

The excavation of the mass grave from the Monastery of the Observance dating from the Great Plague of Marseilles revealed the first evidence of an autopsy on the skull of a 15-year-old boy, performed during the spring of 1722. The reconstruction of the skull allows us to reconstitute the anatomic technique used, which is identical to those described in a surgical book dating from 1708. This research highlights the interest in correlating the biological and historical archives, and brings new anthropological data to the debate on the contagious nature of the plague.

Adolescent↗
PubMed1997

Metabolism of clozapine by human neutrophils: evidence for a specific oxidation of clozapine by the myeloperoxidase system with inhibition of enzymatic chlorination cycle.

The use of clozapine, an unique antipsychotic drug, raises the real problem of drug-induced polymorphonuclear neutrophil cytotoxicity. Clozapine prescription has been restricted due to a 1-2% incidence of drug-induced agranulocytosis. The exact mechanism of this adverse effect is not yet known. The myeloperoxidase-hydrogen peroxide system could play a key role in the initiation of agranulocytosis. Therefore, we have investigated the clozapine effects on hydrogen peroxide and hypochlorous acid, evaluated the peroxidase-mediated metabolism of clozapine by mass spectrometry analysis because myeloperoxidase uses hydrogen peroxide and chloride producing hypochlorous acid in its chlorination cycle, and thus could oxidise clozapine in its peroxidation cycle. First, evidence for inhibition of hypochlorous acid production and scavenging of hydrogen peroxide by clozapine were demonstrated in vitro, in different cell-free and cellular systems. Results are consistent with an inhibition of the myeloperoxidase chlorination cycle when clozapine is oxidised in the peroxidation cycle. Secondly, ion-spray mass spectrometry analysis allowed us to confirm clozapine oxidation by the myeloperoxidase system. Actually, clozapine N-oxide with a m/z at 343 was formed. It could be the final step of the metabolisation of clozapine via two successive univalent oxidations mediated by peroxidase. We suggest that generation of a free cation radical, CLZ(o+), was the initial step. CLZ(o+) is a very reactive species and may play an important role in the onset of agranulocytosis either by direct toxicity or via an immunological mechanism. However, this assumption does not exclude the possible role of other metabolic ways involving, in particular, N-desmethylclozapine.

Antipsychotic Agents↗
PubMed1997

CD4+ T-cell lymphopenia in Q fever endocarditis.

Valvular endocarditis is the most serious complication of chronic Q fever, an infectious disease due to Coxiella burnetii. Although its pathogenesis is poorly understood, the role of the immune system has been evoked. The aim of this study was to investigate lymphocyte subsets in the peripheral blood of infected patients by analyzing the distribution of T- and B-lymphocyte subsets. Since various infectious diseases have been found to be associated with modified antigen expression, we also measured the antigen density of the main lymphocyte markers by quantitative flow cytometry. The absolute values of CD3+ T cells and CD19+ B cells were lower in infected subjects than in controls. The decrease in the CD4+ T-cell count was more pronounced than that in the CD8+ T-cell count, leading to a significantly lower CD4/CD8 ratio in patients. The decreases in CD4+ T cells and CD19+ B cells were correlated with levels of C. burnetii-specific immunoglobulin G, showing that CD4+ lymphopenia is related to the activity of chronic Q fever. Quantitation of antigen expression on lymphocytes showed that CD3, CD4, CD8, and CD19 were expressed similarly in patients and controls. In contrast, CD2 and CD11a expression levels, which are both related to naive and memory phenotypes, were modified in patients. The study of CD45RO and CD45RA expression by CD4+ T cells provided evidence that lymphopenia preferentially affected unprimed lymphocytes.

Adult↗
PubMed1997

Immunological and biological properties of recombinant Lol p 1.

BACKGROUND: Current forms of allergy diagnosis and therapies are based on the use of natural allergenic extracts. Despite strong evidence that higher therapeutic efficacy may be achieved with purified allergens, the purification of multiple allergic components from extracts is a fastidious and sometimes an impossible task. However, the use of recombinant allergens may be an alternative to overcome this problem. OBJECTIVE: In this study, we compared the immunological properties of recombinant (r) Lol p 1 with those of the natural protein. METHOD: We cloned directly the gene encoding Lol p 1 from genomic DNA of ryegrass pollen. This gene was subcloned into the expression vector pMAL-c and expressed as fusion protein. Subsequently, rLol p 1 was cleaved from maltose-binding protein using factor Xa. Using binding inhibition and proliferative assays, we assessed the immunological properties of the recombinant allergens. The capacity of rLol p 1 to trigger basophil histamine release and to elicit a skin reaction was also assessed and compared to those of its natural counterpart. RESULTS: We found that the Lol p 1 gene has no introns since we amplified this gene directly from genomic DNA. We demonstrated that the binding sites of anti-Lol p 1 monoclonal antibody, specific human IgG and IgE antibody are well conserved on rLol p 1 as no difference in the binding inhibition profile was observed when using either natural or recombinant protein. At the T-cell level, rLol p 1 elicited a T-cell response in mice comparable to that observed with the natural protein. In addition, we demonstrated that the biological characteristics of rLol p 1 were comparable to those of the natural counterpart, in that rLol p 1 elicited a skin wheal reaction and induced basophil histamine release in grass-allergic patients only. CONCLUSION: The data indicate that natural Lol p 1 and rLol p 1 shared identical immunological and biological properties.

Allergens↗
PubMed1997

In vitro interaction between dirithromycin or its metabolite, erythromycylamine, and oxidative polymorphonuclear metabolism.

The direct stimulation by neutrophil-infectious bacteria induces an increase in the production of reactive oxygen species which is an important host defense mechanism. Antibiotics that enter rapidly and are concentrated in neutrophils, can stimulate or damage this function. In this study, an in vitro evaluation has been made of the macrolide, dirithromycin, and its active metabolite, erythromycylamine, on the superoxide anion generation by neutrophils in three systems of stimulation: the oligopeptide fMLP, an analogue of bacterial chemotactic factors; the phorbol ester PMA, a direct activator of protein kinase C; and a bacteria strain, Staphylococcus aureus. It has been demonstrated that dirithromycin, at therapeutic plasma concentrations, and its active metabolite have a significant pro-oxidant effect on the two systems: fMLP and bacteria. This effect is greater for dirithromycin than that for erythromycylamine. At higher non-therapeutic concentrations, these substances decrease superoxide generation in the three systems. The effects of these two agents seem to be the result of an intracellular mechanism resulting in the intervention of the oxidative metabolism of neutrophils since no effect was found in the cell-free systems. Therefore, this in vitro study suggests that at therapeutic concentrations, dirithromycin and erythromycylamine could benefit therapy by stimulation of the oxidative metabolism of neutrophils.

Anti-Bacterial Agents↗
PubMed1997

Antioxidant activities of polyphenolic extracts from flowers, in vitro callus and cell suspension cultures of Crataegus monogyna.

Numerous plants synthesize among their secondary metabolites phenolic compounds which possess antioxidant effects. The aim of the present work was to assay the antioxidant activities of phenolics from Crataegus monogyna Jacq. flowers and in vitro tissue culture (calli and cell suspensions) extracts. In the case of tissue culture extracts, the phenolic production is studied at three different stages of one subculture period (initial growth period, increasing and maximal phenolic synthesis phases). Attention was paid to the main categories: flavonoids and proanthocyanidins, and to the principal individual components. Total phenolic amounts decrease in the order: fresh flowers > cell suspension cultures > callus cultures. The antioxidant activities of these different extracts against H2O2 and HOCl, have been determined in vitro. All the extracts are efficient and the scavenging capacity is clearly related to the total phenol content. The scavenging effects of the cell suspension extracts are similar to those of the flowers. Among individual compounds, the flavanol-type derivatives, specially the proanthocyanidin B2, are more efficient. Thus, in vitro plant tissues could be an interesting source of bioactive molecules.

Anthocyanins↗
PubMed1997

Evidence of pin implantation as a means of verifying death during the Great Plague of Marseilles (1722).

The evidence obtained for the methods used in verification of death during the Great Plague of Marseilles in 1722 is presented here. This evidence was gathered during the excavation of a mass grave dating from this epidemic, and is based on two adjacent interments. The technique used at that time was the implantation of bronze pins into the toes. This method is precisely described in the medical treatises dating from this period, which list different death verification methods. The fear of "false death" and the burial of still living people characterized the end of the 17th and the 18th centuries. It should be noted that the main cause of apparent death is presented in the same medical treatises as the plague. This observation is the first anthropological evidence of the use of this forensic method to verify the fact of death.

Adult↗
PubMed1997

[Early postoperative morbidity after hemorrhoidectomy using the Milligan-Morgan technic. A retrospective studies of 1,134 cases].

Milligan and Morgan's procedure is commonly used for the surgical management of haemorrhoids. The aim of our study was to evaluate short term postoperative morbidity. Between 1975 and 1990, 1,134 patients were operated on. Two patients died after operation. The most frequent complications were pain (71%) and urinary retention (16.4%). Hemorrhages (7.6%) resulting in a re-operation occurred in 1% of cases. Other complications were rare and always cured by a specific treatment (stenosis: 2.9%, anal fissure: 0.5%, abscess: 0.6%, fistula in ano: 1.2%). Two patients had anal incontinence partially improved by biofeedback. Hemorrhoidal was 2%. Short term postoperative morbidity is generally low after Milligan and Morgan hemorrhoidectomy, with careful supervision in a surgical department and repeated postoperative care.

Abscess↗
PubMed1996

Monoblastic leukemia in an HIV-infected patient: absence of viral expression in RNA blasts.

A small number of patients seropositive for the human immunodeficiency virus (HIV) have been reported as developing acute non-lymphoblastic leukemia (ANLL). In the cases previously published, the authors never reported a study of the link joining HIV infection and leukemia. We describe here the case of a 41-year-old HIV positive patient who developed ANLL (FAB classification M5). Using molecular techniques, we looked for a direct link between these two co-existing diseases. We showed the absence of HIV expression in the malignant clone, suggesting that the association of ANLL and Acquired Immune Deficiency Syndrome is not a direct consequence of the myeloid precursors infection. Nevertheless a relationship may exist through a disorganization of the bone marrow micro-environment.

Adult↗
PubMed1996

Effects of calcium antagonist diltiazem on leukocyte elastase and on reactive oxygen species production in human neutrophils.

During inflammatory disorders, some proteases and very reactive oxygen metabolites are produced by activated phagocytic cells. These proteases and oxidants are involved in many diseases like tissue injury or atherosclerosis. It was shown in vitro that diltiazem, a calcium channel blocker, had antielastase and antioxidant properties. This drug inhibited the release of elastase by neutrophils in a dose dependent manner when these cells were stimulated by phorbol-myristate-acetate (PMA) or by formyl-methionyl-leucylphenylalanine (fMLP) with an IC50 of 144.5 microM, and 132.8 microM, respectively. Towards the oxidants, the 50% inhibitory concentrations (IC50) of diltiazem are 422 microM, 138 microM and 165 microM for superoxide anion, hypochlorous acid and hydroxyl radical production by PMA stimulated human neutrophils, respectively. In the case of fMLP stimulated human neutrophils, the IC50 for superoxide anion is 78 microM. When human neutrophils were stimulated by dioctanoylglycerol (DiC8) or by calcium ionophore (Ca.I), the IC50 for superoxide anion were 175.5 microM and 186 microM, respectively. When human neutrophils were stimulated by opsonized zymosan (OZ), diltiazem did not show an inhibition of superoxide production in a dose dependent manner. This drug did not act by scavenging elastase or oxidants as demonstrated by cell free models. A mechanism of elastase and oxygen metabolites inhibition by diltiazem has been considered specially toward the mobilization of cytosolic calcium and an inhibition of protein kinase C cannot be excluded. The results suggest that diltiazem might contribute to attenuate the development and the progression of atheroma where oxidants and elastase have been implicated.

Diltiazem↗
PubMed1996

Viscoelastic properties of human arteries. Methodology and preliminary results.

In order to study the biomechanical properties of the arterial wall and to compare arteries with different histologic structures, we designed a device that allows testing of arterial segments under near-physiologic conditions. A hydrodynamic generator simulates systolo-diastolic pressures in an open loop. An intraarterial pressure sensor and a sonomicrometer connected to two piezoelectric crystals placed in diametric opposition on the arterial wall allow computer calculation of compliance, stiffness, midwall radial arterial stress, Young modulus, and incremental modulus for a given arterial segment at a given pressure setting. Seven healthy common carotid artery (CCA) segments and seven healthy (superficial) femoral artery (FA) segments were studied immediately after removal from brain-dead donors between the ages of 18 and 35 years. Histologic examination was performed to determine the density of elastic fibers in the arterial wall. Hysteresis was observed in all segments regardless of pressure settings. Compliance was greater and modulus values and stiffness were lower in CCA than in FA. No evidence of structural change was noted after testing in the circulation loop. These preliminary results open the way to a wide variety of applications for our hydrodynamic circulation loop. Experiments will be undertaken to compare the mechanical properties of arteries before and after cryopreservation.

Adolescent↗
PubMed1996

Left subpancreatic transplexus exposure of the proximal abdominal aorta.

The authors report their experience based on the anatomical study of the celiac region and on the practice of abdominal multiorgan removal for transplantation. They particularly concentrate on the limits and the content of the celiac region of Luschka and particularly: -the position of the celiac axis in relation to the median arcuate ligament of the diaphragm, -the relations of the collateral branches of the abdominal aorta, -the place being taken by the celiac plexus and its situation in relation to the left renal v. From these elements, they describe an original transplexus surgical exposure of the origins of the celiac axis and of the superior mesenteric a. They show the importance of this approach in abdominal vascular surgery and during abdominal multiorgan removal in transplantation.

Aorta, Abdominal↗
PubMed1996

Neuroleptic monitoring: relation between antipsychotic efficiency and radioreceptor assay of serum haloperidol.

OBJECTIVE: We report preliminary results from use of a radioreceptor assay (RRA) to measure serum haloperidol levels and their relation to clinical response and adverse effects in 19 psychotic patients with positive symptoms treated with haloperidol. METHODS: Blood samples were taken on Days 7, 14 and 21. Clinical evaluation was based on the PANSS, and UKU scales. The D2 antidopaminergic RRA was used to measure haloperidol serum levels. RESULTS: Our results show a correlation between psychosis with positive symptoms assessed by positive scores in the PANSS and the serum drug level measured by RRA concentrations. The observed relationship made it possible to establish a therapeutic serum range of haloperidol equivalents 15-30 ng/ml-1. This range contained no "non-responders". Analysis of the correlation between each item on the positive subscale of the PANSS and the RRA concentration suggested that there was no specific symptom of psychosis closely related to RRA concentration during the first 15 days of treatment. In the third week, however, certain specific symptoms were closely connected to the RRA concentration. CONCLUSION: From these results, it can be concluded that antipsychotic activity can be related to blockade of serum D2 dopamine receptors. In future would be desirable to monitor neuroleptic treatment in this way. The study also showed that the antipsychotic treatment did not correct any specific component of the psychosis during the first stage of the treatment but that it did so at later times.

Adult↗
PubMed1996

Stability and compatibility studies of zorubicin in intravenous fluids and PVC infusion bags.

The stability of zorubicin (ZOR) in admixtures for continuous intravenous infusion was studied. ZOR was reconstituted and diluted to 600 micrograms ml-1 for simulated infusion and to 250 and 1000 micrograms ml-1 for storage in poly(vinyl chloride) (PVC) bags containing 5% dextrose injection or 0.9% sodium chloride injection (0.9% NaCl). Bags were then stored at refrigerated temperature (4 degrees C) and in the dark for 24 h. ZOR concentrations in each admixture were tested by stability-indicating high-performance liquid chromatographic (HPLC) assay with ultraviolet detection. No substantial loss of ZOR was observed during simulated infusions (n = 4) using PVC infusion bags and administration sets over a 1 h infusion. The drug stored at 4 degrees C in the dark in PVC bags showed that it is highly unstable at 250 micrograms ml-1 in 0.9% NaCl injection and in 5% dextrose injection. On the other hand, under the same storage conditions, at 1000 micrograms ml-1, ZOR is more stable in 0.9% NaCl injection (6 h) than in 5% dextrose (4 h). The reported superior stability of the 1000 micrograms ml-1 in 0.9% NaCl can be explained, at least in part, by the difference in pH. Changes in pH, particularly a decrease, seem to affect adversely the stability of ZOR. In fact, ZOR is rapidly converted into daunorubicin, the dominant degradation product, which is more cardiotoxic than the parent drug. Therefore, several precautions must be observed when the commercial product (Rubidazone) is prepared and reconstituted in i.v. fluids and containers.

Antibiotics, Antineoplastic↗
PubMed1996

Effect of the protein kinase C inhibitor GF 109 203X on elastase release and respiratory burst of human neutrophils.

1. The effects of bisindolylmaleimide GF 109 203X, reported to be a potent and highly selective inhibitor of protein kinase C (PKC), have been investigated on some human neutrophil functions. 2. GF 109 203X prevented O.2- production by NADPH-oxidase whatever the stimulus used for polymorphonuclear neutrophil (PMN) activation: directs PKC activators like phorbol myristate acetate (PMA) and dioctanoylglycerol, calcium ionophore (A23187), or receptor agonists like fMet-Leu-Phe (fMLP) and opsonized zymosan. 3. The effect of GF 109 203X was also examined on elastase exocytosis by neutrophils. PMA-mediated release was prevented by GF 109 203X. However, GF 109 203X had no effect on exocytosis induced by A23187 and the effect of this compound on the fMLP response changed according to its concentration. 4. These data suggest that PKC might be essential for stimulus-mediated O.2- production and also that PKC plays only a minor role in elastase secretion as compared to the role of the cytosolic calcium level.

Calcimycin↗
PubMed1996

Comparison of histamine-releasing factor recovered from skin and peripheral blood mononuclear cells of patients with chronic idiopathic urticaria.

BACKGROUND: The pathogenesis of chronic idiopathic urticaria is characterized by defective histamine release. Skin mast cells show an increased release of histamine while circulating basophils are less responsive to immunologic stimulus. OBJECTIVE: The purpose of the study was to examine and compare the production of the histamine-releasing factor in the skin and within the peripheral blood of patients with chronic idiopathic urticaria and normal control subjects, as a possible factor responsible for the difference observed in the releasability of both skin mast cells and basophils. METHODS: Using the skin chamber technique, histamine-releasing factor production and histamine concentration were assessed in normal-appearing skin of patients with chronic idiopathic urticaria (n = 12) and normal controls (n = 5) over a 2-hour observation period. In both groups, histamine-releasing factor production by peripheral blood mononuclear cells was also measured. RESULTS: The weighted average of histamine-releasing factor production during the 2-hour observation period was higher in the non-lesional skin of patients with chronic idiopathic urticaria as compared with normal controls (5.6 +/- 1.4% versus 0.7 +/- 0.6%, P < .01). In contrast, less histamine-releasing factor was produced by peripheral blood mononuclear cells in chronic urticaria as opposed to normal controls (17.2 +/- 2.1% versus 25.7 +/- 2.8%, P < .03). Spontaneous histamine concentration was not significantly different in patients with chronic urticaria than in normal controls. CONCLUSION: Histamine-releasing factor production is increased in the skin, and decreased in the peripheral blood of patients with chronic idiopathic urticaria when compared with nonatopic controls. The lower production of histamine releasing factor in the blood could be explained by the migration of activated T-lymphocytes in the skin.

Adolescent↗