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Biomedical subjects

C Brunet

Publications and source records attributed to C Brunet.

At least 55 records · Page 3Linked to original sources
PubMed1999

Combination antiretroviral therapy including ritonavir in children infected with human immunodeficiency.

OBJECTIVE: To assess the efficacy of combination therapy that includes ritonavir in HIV-1 infected children. DESIGN: A monocentric retrospective study. PATIENTS AND METHODS: Twenty-two children with a minimum follow-up of 6 months under triple therapy including ritonavir were analysed for treatment efficacy. At entry, all the patients were protease inhibitor naive and all but two had received previous antiretroviral therapy during a median period of 5 years. Their initial median CD4+ lymphocyte count and viral load were 121 x 10(6)/l and 5.08 log10 copies/ml, respectively. Clinical and biological evaluation included clinical assessment every 6 weeks and determination of CD4 cell count and HIV-RNA concentration every 3 months. RESULTS: Median length of follow-up on triple therapy was 15 months (range: 7-21 months). Neither progression in the CDC classification nor death occurred. No significant change in mean weight SD scores was noted when baseline values were compared with values obtained after 1 year of triple therapy. Median CD4 count increases were of 210 x 10(6)/l, 415 x 10(6)/l, and 472 x 10(6)/l cells at 6, 12, and 18 months, respectively. Among the patients baseline characteristics, neither age nor initial CD4 cells count influenced the magnitude of immunologic improvement. There were median decreases of 1.14, 0.95, and 1.5 log10 per ml of plasma in the concentration of viral RNA at 6, 12, and 18 months respectively. Seven patients maintained an undetectable viral load when under treatment. The introduction of at least one new reverse transcriptase inhibitor at the initiation of triple therapy correlated significantly with a greater viral suppression. CONCLUSION: Despite variable viral response, antiretroviral-experienced HIV-infected children demonstrated a substantial CD4 cell increase during a median period of 15 months of ritonavir containing combination therapy.

Adolescent↗
PubMed1999

Differential regulation of killer cell Ig-like receptors and CD94 lectin-like dimers on NK and T lymphocytes from HIV-1-infected individuals.

NK and T lymphocytes share various cell surface receptors, including NK receptors for MHC class I molecules (NKR). NKR include killer cell Ig-like receptors (KIR) and lectin-like dimers which are composed of the invariant CD94 associated with a variety of NKG2 molecules. The combination of KIR and CD94/NKG2 dimers expressed on NK and T cell subsets defines a repertoire of MHC class I recognition. Engagement of NKR by cognate MHC class I molecules governs T and NK cell activation. We investigated the NKR distribution on NK and T cell subsets from uninfected and HIV-infected individuals, according to the clinical status, the absolute numbers of CD4+ T cells as well as the plasmatic viral load of the patients. We show that the KIR distribution on NK cells is not affected by HIV-1 infection, whereas the absolute numbers of T cells expressing specific KIR members (CD158b, p70) transiently increase in early stages of HIV infection. By contrast, the percentages of NK and T cells which express CD94 dimers increase in parallel with the disease. These results document a differential regulation of KIR and CD94 lectin-like dimers during the course of a chronic viral infection in humans and further suggest that both types of NKR are independently regulated.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Selection criteria for internal rectal prolapse repair by Delorme's transrectal excision.

PURPOSE: The aim of this study was to review our results of Delorme's transrectal excision for internal rectal prolapse, with a view to determining preoperative selection criteria associated with a satisfactory outcome. METHODS: Between 1992 and 1998, 20 patients with internal rectal prolapse underwent Delorme's transrectal excision. The last patient was excluded from the study because of a follow-up period shorter than six months. The remaining 19 patients were prospectively followed up and classified into two groups according to their preoperative selection criteria. Group I consisted of eight patients operated on between January 1992 and October 1993 who were selected for surgery after medical treatment during a three-month period failed to improve symptoms. Initial results were reviewed, with a follow-up of at least six months, to assess predictive criteria correlating with poorer surgical outcome. These adverse criteria were used to exclude patients from selection into Group II, which included 11 patients operated on between June 1994 and June 1997. In each group the degree of improvement of symptoms was graded: Grade 1 = complete improvement with resolution of all symptoms; Grade 2 = significant improvement with resolution of dyschezia but not of other symptoms; Grade 3 = no improvement; and Grade 4 = worsened condition or reoperation. The two groups were compared according to ultimate outcomes. RESULTS: Of the Group I patients, three had preoperative chronic diarrhea, one had proximal internal rectal prolapse with rectosacral separation at defecography, and the other two were incontinent to liquid stool. An additional patient had incontinence to liquid stool but no diarrhea. Three other patients had major perineal descent (>9 cm). Results were Grade 1 for one patient, Grade 2 for one patient, Grade 3 for five patients, and Grade 4 for one patient (subsequent abdominal rectopexy). Data review showed that proximal internal prolapse with rectosacral separation at defecography, preoperative chronic diarrhea, fecal incontinence, and descending perineum (>9 cm on straining) were associated with a poorer outcome (Grades 3 and 4). These adverse criteria were used to exclude patients from selection into Group II. In this group results were Grade 1 for seven patients and Grade 2 for four patients. During the course of follow-up (mean, 43; standard deviation, 19; range, 8-73 months), outcome was better in Group II (P = 0.007). CONCLUSION. These data suggest that a favorable outcome can be achieved after Delorme's transrectal excision for internal rectal prolapse by applying stringent patient-selection criteria.

Adult↗
PubMed1999

Effects of PVC bags sterilization process on the 5-fluorouracil stability.

The stability and compatibility of 5-fluorouracil (5-FU) in undiluted or diluted admixtures stored in beta-radiation sterilized portable poly(vinyl chloride) (PVC) infusion bags were investigated. Admixtures containing 5-FU 50 mg ml(-1) not diluted or 25 mg ml(-1) diluted in 0.9% sodium chloride injection were placed in 100 or 250 ml empty PVC reservoirs sterilized initially by beta-irradiation. They were protected from light and placed at 37 degrees C. Two ml quantities were withdrawn immediately after preparation and after storage for 1, 2, 3, 4, 5, 6, 7 and 14 days. For each condition, samples from each admixture were tested for drug concentration by stability-indicating high-performance liquid chromatography. The admixtures were also monitored for precipitation, color change and pH. Evaporative water loss from the containers was also measured. 5-FU was compatible with PVC containers in all tested conditions for 14 days. No loss of drug and no color change were detected throughout the storage period. pH values were stable and neither precipitation nor loss of water through the reservoirs was observed when drug 50 or 25 mg ml(-1) (diluted using 0.9% sodium chloride) was stored in 100 ml capacity polyvinyl PVC bags. However, when stored in 250 ml capacity PVC bags, the 5-FU solution showed precipitation after 13 and 14 days of storage, but no drug loss was detected due to a substantial loss of water. The precipitation of the drug was due to the decrease of pH induced by the dehydrochlorination of PVC during beta-irradiation leading to the formation of hydrochloric acid in solution. Differences observed between 100 and 250 ml capacity bags can be explained by the greater area of PVC present in 250 ml reservoirs, and consequently more HCl formed. Finally, more plasticizer, di-(2-ethylhexyl) phthalate (DEHP), was then detected in drug solutions stored in 250 ml PVC bags. So, we recommend the use of 100 ml bags to store 5-FU at longer storage times and higher temperatures.

Antimetabolites, Antineoplastic↗
PubMed1999

Stability, compatibility and plasticizer extraction of quinine injection added to infusion solutions and stored in polyvinyl chloride (PVC) containers.

The stability of quinine was determined in various diluents and in polyvinyl chloride (PVC) containers. The release of diethyhexyl phthalate (DEHP) from PVC bags into intravenous infusions of quinine was also measured. We used an injection of two doses of quinine; quiniforme at 500 mg and quinimax at 400 mg in either 250- or 500-ml PVC infusion bags containing 5% dextrose, to give initial nominal concentrations of 2 or 1 mg ml(-1) quiniforme and 1.6 or 0.8 mg ml(-1) quinimax, the mean concentrations commonly used in clinical practice. Samples were assayed by stability-indicating high-performance liquid chromatography (HPLC) and the clarity was determined visually. Experiments were conducted to determine whether the stability and compatibility of quinine would be compromised, and whether DEHP would be leached from PVC bags and PVC administration sets during storage and simulated infusion. There was no substantial loss of quiniforme and quinimax over 1- or 2-h simulated infusion irrespective of the diluent, and storage during 8 h at 22 degrees C, 48 or 72 h at 4 degrees C and 96 h at 45 degrees C. Leaching of DEHP was also detected during simulated infusion delivery using PVC bags and PVC administration sets. The quantity was less than 2 microg ml(-1). During storage at 4 degrees C and room temperature the leaching of DEHP was low, but when the temperature was 45 degrees C the quantity was high, 21 microg ml(-1). To minimise patient exposure to DEHP, quinine solutions with all drugs should be infused immediately or stored for a maximum of 48 h at 4 degrees C.

Antimalarials↗
PubMed1999

Evaluation of the effects of Gd complexes used as magnetic resonance imaging contrast agents, on superoxide dismutase: comparison of two methods.

Investigations are currently being made into the safety of gadolinium complex contrast agents used in Magnetic Resonance Imaging. Their hyperosmolality or potential Gd3+ release is evoked as a cause of various anaphylactoid reactions to be observed in humans after intravenous injection. An estimation has already been made of their effects on the liberation of reactive oxygen intermediates by neutrophils. The purpose of this study was to find a suitable method to measure SOD activity in the presence of these hyperosmolar solutions, and to evaluate their action on this activity. Two techniques were compared to measure this activity. Results and statistical analysis showed that pyrogallol autoxidation was greatly affected by solution osmolalities, whereas ferricytochrome C reduction was not. Gadopentetate dimeglumine and gadoterate meglumine seemed to activate Cu, Zn SOD in vitro, but did not exhibit any SOD-like activity. Gadodiamide did not interfere with this system of detoxication.

Contrast Media↗
PubMed1999

Omeprazole-induced leukopenia. A case report.

BACKGROUND: Omeprazole has been marketed in France since 1989, for the healing of peptic ulcers, erosive reflux oesophagitis, and the Zollinger-Ellison syndrome. However, the drug has been associated with serious adverse reactions, including haemolytic anaemia and acute interstitial nephritis. More recently, an autoimmune syndrome induced by omeprazole has been described. OBJECTIVE: We present here a clinical history and an in vitro test of cytotoxicity linking leukopenia to omeprazole. RESULTS: A 37-year-old woman was hospitalized in the intensive care unit of our hospital with acute pulmonary insufficiency secondary to pneumonia. 72 h after starting omeprazole treatment, a decrease in leucocyte count was observed. The leukopenia was maximal on day 22: total white cell count was 2. 1x109/l, and neutrophil count was less than 0.75x109/l. In order to find the cause of this leukopenia, an in vitro cytotoxicity test was performed. The test was positive only when patient neutrophils and patient serum were in the presence of omeprazole. This cytotoxicity seems to be complement-dependent, as in the presence of heated serum, the omeprazole toxic effect was substantially reduced. CONCLUSION: This case report suggests that the leukopenia was associated with omeprazole.

Adult↗
PubMed1999

Comparative oxidation of loxapine and clozapine by human neutrophils.

The clozapine-induced agranulocytosis could be due to the formation of a reactive intermediate formed in polymorphonuclear neutrophils and granulocyte precursors with the myeloperoxidase-hydrogen peroxide system. On the contrary, no case of agranulocytosis has been described for loxapine, an other neuroleptic drug with a very close structural analogy. We have compared the clozapine and loxapine interaction with the oxidative burst and particularly with this enzymatic complex. On the one hand, the assay of the oxidative species demonstrated a different impact for the two neuroleptics. The 50% inhibitory concentration was 92 microM for hydrogen peroxide and 40 microM for hypochlorous acid for loxapine. The loxapine target is located before the myeloperoxidase-hydrogen peroxide system in the oxidative stream, whereas clozapine diverts the chlorination pathway of the enzyme. On the other hand, the in vitro metabolism of drugs by the myeloperoxidase-hydrogen peroxide system has been investigated by mass spectrometry. Loxapine remains inert but clozapine undergoes the oxidation. The glutathione or ascorbate addition in the medium leads to a removal of the oxidation. Glutathione is able to trap the toxic intermediate and could avoid its formation.

Antioxidants↗
PubMed1999

Effects of two antihypertensive agents, labetalol and metoprolol, on the production of reactive oxygen species by normal polymorphonuclear leukocytes in vitro.

OBJECTIVE: Increased lipid peroxidation is a putative causal factor for preeclampsia. Because oxygen free radicals are involved in inducing the lipid oxidation chain reaction, we evaluated two beta adrenoreceptor blockers, labetalol and metoprolol, currently used for treating hypertension with regard to their ability to inhibit the formation of reactive oxygen species during respiratory burst of human normal polymorphonuclear leukocytes in vitro. METHODS: We determined whether labetalol or metoprolol have antioxidative activity in a model of polymorphonuclear leukocytes stimulated in vitro with phorbol-12-myristate-13-acetate (PMA) and N-formyl-methionin-leucin-phenylalanin (fMLP). We also studied the scavenging properties of these two drugs using acellular systems. RESULTS: Labetalol inhibits O2-. production by neutrophils activated by fMLP (IC50 = 17.5 mg/L) and weakly by PMA (43.6% inhibition at 100 mg/L). It also possesses a significant activity on OH. production (IC50 = 65 mg/L) that may depend in part on its ability to interfere with iron in the Fenton reaction. The same assays performed with metoprolol did not show any inhibitory effect on O2.- generation. It decreased weak OH. production by neutrophils, as a result of cellular and scavenging effects. CONCLUSION: Labetalol shows important antioxidative properties in vitro with regard to normal leukocyte oxidative metabolism.

Antihypertensive Agents↗
PubMed1999

Time and concentration dependent influence of dirithromycin on neutrophils oxidative burst.

Dirithromycin is a 14-membered macrolide antibiotic, well known to yield high intragranulocytic levels after several hour exposure. We chose therefore to investigate oxidative metabolism after prolonged incubation periods with neutrophils. Neutrophil generation of reactive oxygen species, represented by superoxide anion, was assessed after fMLP or Staphylococcus aureus-induced activation of the respiratory burst. Cellular uptake of the drug was assessed concurrently, in order to attempt a correlation with time-dependent modifications of the cellular oxidative status. For 1 hour exposure time, a pro-oxidant effect was reported for lower concentrations, achievable during therapeutic administration, whereas the highest ones promoted a potent anti-oxidant effect. After prolonged incubation times, the anti-oxidant effect alone was reported, with time-dependent modifications of IC50 values. These values could be correlated with intracellular accumulation of the drug. The anti-inflammatory activity reported here for high dirithromycin concentrations, could be nevertheless clinically relevant, since dirithromycin cellular uptake extends beyond 4 hours.

Anti-Bacterial Agents↗
PubMed1999

Serum opioid activity after physical exercise in rats.

In order to study the effect of exercise on the total serum opioid activity, female rats were trained for 3 weeks on a motor-driven treadmill and the experiment was ended by a final strenuous run until exhaustion. The serum samples were taken immediately after the final run and were analyzed by radioreceptor assay. Despite considerable interindividual variations, serum opioid activity, expressed in met-enkephalin equivalents (ME eq +/- S.D.), was significantly higher in the exercising group (74.5+/-50.5 pmol ME eq/ml) than in the control group (35.7+/-20.2 pmol ME eq/ml). Because of the much lower molar levels of beta endorphin and met-enkephalin, this result suggests that many other opioid peptides might be involved in that increase.

Animals↗
PubMed1998

In vitro interaction between spiramycin and polymorphonuclear neutrophils oxidative metabolism.

PMNs are a major component of body defense against microbial invasion, involving reactive oxygen species in great quantity, which could benefit from antibiotic therapy. Recently, possible antibiotic effects on phagocyte functions (impairment or stimulation of reactive oxygen species production) were studied. In our study, an in vitro evaluation was made on macrolide activity on phagocyte respiratory burst functions, using assay of superoxide anion (O2.-) in response to four stimuli systems: N-formyl Met-Leu-Phe (fMLP), an analogue of bacterial chemotactic factors; 4 beta-phorbol 12-myristate 13-acetate (PMA), a direct activator of protein kinase C (PKC); calcium ionophore (A23187), which acts directly on calcium influx; and a bacterial strain, Staphylococcus aureus. We have shown that spiramycin, at therapeutic plasma concentrations, increased O2.- generation by bacteria and fMLP-stimulated PMNs, with rate of 26% for 1 microgram ml-1 and 34% for 5 micrograms ml-1, respectively. This pro-oxidant effect, however, weaker, was observed when PMNs were stimulated by PMA. A weak anti-oxidant effect was observed with A23187. For higher concentrations, spiramycin decreased strongly O2.- production, with IC50 values of 74 micrograms ml-1, 154 micrograms ml-1, 296 micrograms ml-1 and 400 micrograms ml-1 when PMNs were stimulated with bacteria, A23187, fMLP and PMA, respectively. The effect of spiramycin seemed to result from an intracellular mechanism by intervention of PMN oxidative metabolism (NADPH-oxidase activation), rather than a simple chemical interaction, because no effect has been observed in acellular models. For higher spiramycin concentrations, the decrease of O2.- production observed could not be taken into consideration because this concentration was not used in therapy. The enhanced of O2.- production observed could be used in therapy, so as to increase PMNs bactericidal activity.

Anti-Bacterial Agents↗
PubMed1998

[Malignant tumors of the ampulla of Vater. Results of radical excision. A study of 39 cases].

STUDY AIM: From 1971 to 1995, 39 patients underwent curative resection of a malignant tumor of the ampulla of Vater. The aim of this retrospective study was to report long-term results and to determine factors influencing survival in these patients. PATIENTS AND METHODS: Data was collected from patient record analysis, correspondence with patients, their family or general physician. Kaplan-Meier method was used to compare survival data by the log-rank test. Multivariate analysis evaluated the impact of each variable on survival. Values with a P value of 0.05 or less were considered statistically significant. RESULTS: Resection consisted of pylorus preserving pancreaticoduodenectomy (n = 21) or pancreatico-duodenectomy associated with an antrectomy (n = 18). Overall mortality rate after resection was 10% (n = 4). General and specific morbidity rates were 71% and 2.5%. During the course of the follow-up (completeness: 100%) mean survival was 80 months (median: 37 months, range: 6-227 months). Five-year survival rate was 35%. Factors favorably influencing long-term outcome were exposed protruding and well differentiated tumors (P = 0.03, P = 0.01, respectively) and negative lymph node status (P = 0.0001). Prognosis was poorer if tumor was extended into the pancreas (P = 0.04). Among proposed histoprognostic classifications (classifications of Martin, Talbot, Shiraï, Yamaguchi), an excellent correlation was obtained only with TNM classification (P = 0.0001). CONCLUSION: Results of the present study suggest that prolonged survival can be obtained following radical resection of a malignant tumor of the ampulla of Vater, especially for exposed protruding and well differentiated tumors, without extension into the pancreas or lymph node metastasis. TNM classification provides an excellent predictive value and should be used more systematically.

Adult↗
PubMed1998

Assessment of the trypsin-like human prostatic kallikrein, also known as hK2, in the seminal plasma of infertile men: respective contributions of an ELISA procedure and of Western blotting.

Human seminal plasma (SP) is a unique source of kallikreins. Prostate-specific antigen (hK3), which is a chymotrypsin-like human prostatic kallikrein (CHPK), and its cousin protein (hK2), which is recognized as a trypsin-like human prostatic kallikrein (THPK), have been assessed in infertility disorders to test the hypothesis that oligoasthenoteratozoospermia (OAT) is associated with an abnormal prostatic function. Monoclonal antibodies specific for THPK (hK2) were produced by Immunova, Canada, and used to develop a new enzyme-linked immunosorbent assay procedure and to perform Western blot analyses in SP. The immunoradiometric assay from Hybritech Inc., San Diego, Calif., was selected for CHPK (hK3) measurements in SP. Determinations of the THPK and of CHPK contents in SP from four groups of subjects were performed after validation of the assays. The concentration of both kallikreins was similar in three groups of infertile men, and no statistical difference from the control group was recorded. Western blot analysis confirmed the existence of different molecular forms of both kallikreins in SP. Generally, these molecular forms were not affected by infertility disorders except when obstructive azoospermia led to the exclusion of seminal vesicles, which are the sources of protein C inhibitor (PCI). No THPK-PCI complex was observed because THPK, unlike CHPK, is bound mainly to PCI within a few minutes after ejaculation. These data suggest that measurements of kallikreins in the SP of infertile men are much less useful than evaluation of their different molecular forms. Specifically, the absence of THPK-PCI appears to be a reliable feature of obstructive azoospermia, and this test should be routinely practiced in andrology laboratories.

Blotting, Western↗
PubMed1998

Stability study of fotemustine in PVC infusion bags and sets under various conditions using a stability-indicating high-performance liquid chromatographic assay.

The stability and compatibility of fotemustine, a nitrosourea anticancer agent, in 5% dextrose solution with polyvinyl chloride (PVC) containers and administration sets were studied under different conditions of temperature and light. The drug was diluted to 0.8 and 2 mg ml(-1) in 100 or 250 ml 5% dextrose injection solutions for 1-h simulated infusions using PVC bags and administration sets with protection from light. After preparation in the PVC bags containing 5% dextrose, fotemustine was also prepared at the same concentrations and stored at 4 degrees C for 48 h and at room temperature (22 degrees C) or at sunray exposure ( > 30 degrees C) over 8 h with or without protection from light. The solution samples were removed immediately at various time points of simulated infusions and storage, and stored at -20 degrees C until analysis. The physical compatibility with PVC and chemical stability in solution of fotemustine were assessed by visual examination and by measuring the concentration of the drug in duplicate using a stability-indicating high-performance chromatographic assay. When admixed with a 5% dextrose solution, fotemustine 2 and 0.8 mg ml(-1) was compatible and stable over 1-h of simulated infusion using PVC bags through PVC administration sets with protection from light. On the other hand, in the same diluent, fotemustine was compatible and stable with PVC bags for at least 8 h at 22 degrees C with protection from light and for at least 48 h at 4 degrees C with protection from light. There were no pH variation, no visual change, no color change, no visible precipitation and no loss of the drug. Conversely, when the solutions were exposed to light (ambient or solar), the drug concentration decreased rapidly, leading to the production of a degradation product as shown by mass spectral analysis and a discoloration of the solutions. Finally, in all cases, no DEHP (di-2-ethylhexyl phthalate) was detected in the injection solution.

Chromatography, High Pressure Liquid↗
PubMed1998

Azithromycin impact on neutrophil oxidative metabolism depends on exposure time.

Several antimicrobial agents have already been investigated relating to their influence on neutrophil ROS generation. Azithromycin provides, a dose-related anti-oxidant effect, after 15 min incubation, with the stimulating agent FMLP, as well with PMA or S. aureus. This finding was however obtained with concentrations not considered in therapeutics. Since short incubation times are not representative of the physiological situation, and since azithromycin is characterized by prolonged high concentrations within phagocytes, the same experiments were performed over 2 and 4 h exposures. A time-dependent anti-oxidant effect was then reported. The maximum effect was obtained with PMA (IC50 were 856 and 30 micrograms/ml for 15 min and 4 h incubation times respectively). Time-dependent modifications of neutrophil oxidative metabolism seem to be correlated with intracellular concentrations. Depressed oxidative metabolism might be related neither to azithromycin cellular toxicity, nor to superoxide scavenging properties. By increasing exposure periods, therapeutic concentrations could therefore lead to an anti-inflammatory effect, potentially of clinical interest since associated with bacteriostatic activity.

Anti-Bacterial Agents↗