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F Bayle

Publications and source records attributed to F Bayle.

At least 19 recordsLinked to original sources

Tolerability of enteric-coated mycophenolate sodium to 1 year in combination with cyclosporine and corticosteroids in renal transplant recipients.

Enteric-coated mycophenolate sodium (EC-MPS) is therapeutically equivalent to mycophenolate mofetil, but delays release of mycophenolic acid until it reaches the small intestine. De novo renal transplant patients taking part in a 12-month, multicenter, randomized study received cyclosporine microemulsion (CsA-ME, early or delayed to day 6), EC-MPS, steroids, and interleukin-2 antagonist induction. Tolerability data relating to EC-MPS are reported. Ninety-seven patients were randomized to early CsA-ME and 100 patients to delayed CsA-ME. Median daily dose of EC-MPS was 1440 mg at all time points throughout the 12-month period. The most frequently reported adverse events were constipation, anemia, urinary tract infection, abdominal pain, leukopenia, and cytomegalovirus infection; there were four malignancies. Fifty patients (24.6%) discontinued EC-MPS prematurely by 12 months, including 42 patients (84%) who discontinued owing to adverse events. No patient discontinued treatment because of gastrointestinal adverse events. Two-thirds of patients (137 [67.5%]) maintained full EC-MPS dose throughout the 12-month study and did not require any dose reduction or dose interruption. EC-MPS is well tolerated in de novo renal transplant recipients when administered in combination with CsA-ME and steroids, with low rates of dose reductions or interruptions. Gastrointestinal adverse events were responsible for dose reduction or interruption in only 5% of patients.

Adrenal Cortex Hormones↗

A positron emission tomography (PET) study of cerebral dopamine D2 and serotonine 5-HT2A receptor occupancy in patients treated with cyamemazine (Tercian).

RATIONALE: Cyamemazine (Tercian) is an antipsychotic drug with anxiolytic properties. Recently, an in vitro study showed that cyamemazine possesses high affinity for serotonin 5-HT(2A) receptors, which was fourfold higher than its affinity for dopamine D(2) receptors (Hameg et al. 2003). OBJECTIVES: The aim of this study is to confirm these previous data in vivo in patients treated with clinically relevant doses of Tercian. METHODS: Eight patients received 37.5, 75, 150 or 300 mg/day of Tercian depending on their symptomatology. Dopamine D(2) and serotonin 5-HT(2A) receptor occupancies (RO) were assessed at steady-state plasma levels of cyamemazine with positron emission tomography (PET), using [(11)C]raclopride and [(11)C]N-methyl-spiperone, respectively. The effective plasma level of the drug leading to 50% of receptor occupancy was estimated by fitting RO with plasma levels of cyamemazine at the time of the PET scan. RESULTS: Cyamemazine induced near saturation of 5-HT(2A) receptors (RO=62.1-98.2%) in the frontal cortex even at low plasma levels of the drug. On the contrary, occupancy of striatal D(2) receptors increased with plasma levels, and no saturation was obtained even at high plasma levels (RO=25.2-74.9%). The effective plasma level of cyamemazine leading to 50% of D(2) receptor occupancy was fourfold higher than that for 5-HT(2A) receptors. Accordingly, individual 5-HT(2A)/D(2) RO ratios ranged from 1.26 to 2.68. No patients presented relevant increased prolactin levels, and only mild extrapyramidal side effects were noticed on Simpson and Angus Scale. CONCLUSION: This in vivo binding study conducted in patients confirms previous in vitro findings indicating that cyamemazine has a higher affinity for serotonin 5-HT(2A) receptors compared to dopamine D(2) receptors. In the dose range 37.5-300 mg, levels of dopamine D(2) occupancy remained below the level for motor side effects observed with typical antipsychotics and is likely to explain the low propensity of the drug to induce extrapyramidal side effects.

Adult↗

A case of arthritis caused by cytomegalovirus after kidney transplantation.

Cytomegalovirus (CMV) is the leading cause of infectious complications after organ transplantation. We report the case of a 55-year-old renal transplant recipient who presented with CMV infection 2 months after transplantation. During oral ganciclovir treatment (5 weeks after interruption of intravenous ganciclovir), he experienced a sharp pain in the right shoulder. Examination was normal, but CMV antigenemia remained positive with 30 cells/300,000. He underwent a shoulder puncture, which confirmed the presence of CMV in the articular fluid after evaluation by polymerase chain reaction gene amplification. The patient recovered from his arthritis of the shoulder, and antigenemia became negative after 3 weeks of parenteral ganciclovir. We describe a CMV arthritis that occurred despite a curative treatment for CMV disease, and comment on the pathogenesis of this infection, the pharmalogical failure, and dosing or treatment duration.

Arthritis↗

Reduction of extracellular dopamine and metabolite concentrations in rat striatum by low doses of acute cyamemazine.

The low incidence of extrapyramidal effects with atypical neuroleptics has been ascribed to their 5-HT(2A)- and 5-HT(2C)-serotonin receptor antagonistic properties. On the other hand, the acute increase in striatal dopamine release by submaximal dopamine D(2) autoreceptor blockade can be respectively reduced and increased by 5-HT(2A)- and 5-HT(2C)-antagonists. Cyamemazine is a neuroleptic D(2)- and 5-HT(2A)-receptor antagonist, with small antagonistic activity at 5-HT(2C) receptors and low incidence of extrapyramidal side effects. Therefore, submaximal cyamemazine was tested in rats for its acute action on the extracellular concentrations of dopamine and dopamine metabolites (DOPAC: 3,4,dihydroxyphenylacetic acid and HVA: 4-hydroxy-3-methoxy-phenyl-acetic acid) in the corpus striatum. The serotonin metabolite 5-HIAA (5-hydroxy-indole-acetic acid) was measured in parallel. Rats prepared for microdialysis (striatum) were intraperitoneally given cyamemazine 1 mg/kg, 5 mg/kg or vehicle ( n=4 in each group). Dopamine, DOPAC, HVA and 5-HIAA concentrations in perfusates under basal conditions and after stimulation by high K(+) were measured by HPLC coupled to electrochemical detection. Cyamemazine 1 mg/kg significantly reduced extracellular concentrations of basal dopamine (-77%), DOPAC (-54%), HVA (-54%) and 5-HIAA (-65%). No such effects were seen with the dose of cyamemazine 5 mg/kg or for K(+)-evoked dopamine release. In conclusion, submaximal cyamemazine can acutely reduce basal dopamine release and metabolism in the rat striatum. Such unusual action can be explained by the original pharmacological profile of cyamemazine (potent D(2)- and 5-HT(2A)-antagonist, with small antagonistic activity at 5-HT(2C) receptors). Further experiments are required to explain the low incidence of extrapyramidal side actions with cyamemazine.

3,4-Dihydroxyphenylacetic Acid↗

[Focus on Islets of Langerhans transplantation].

INDICATIONS: There are two types of indications for Langerhans islets transplantation, patients with type 1 diabetes mellitus who have a functional kidney graft but who cannot be candidates for total pancreas transplantation, and soon, patients without renal failure who develop particularly uncontrollable diabetes mellitus. SEVERAL BASIC CONDITIONS: Several conditions are required for the success of Langerhans islet transplantation: a laboratory with demonstrated skill is isolating islets, a sufficiently large number of islets for injection (600,000 for a 60-kg patient), fresh islets harvested within less than 24 hours before transplantation, effective immunosuppressive treatment with no toxic effect on Langerhans islets. The injection is a simple procedure performed under local anesthesia via transhepatic catheterization of the portal vein. RESULTS: Through 2000, 10% to 20% of implanted grafts were functional at 1 year. Islets survival has exceeded 80% at 1 year. The gold standard for success is withdrawal of insulin therapy and normal glucose control. Islets grafts will undoubtedly become the next important step in the treatment of type 1 diabetes mellitus, but other techniques are also envisaged for the future.

Age Factors↗

Human islet transplantation network for the treatment of Type I diabetes: first data from the Swiss-French GRAGIL consortium (1999-2000). Groupe de Recherche Rhin Rhĵne Alpes Genève pour la transplantation d'Ilots de Langerhans.

AIMS/HYPOTHESIS: Improvements in islet transplantation require clinical series large enough to implement controlled new strategies. The goal of this study was to demonstrate the feasibility of a multicentre network for islet transplantation in Type I (insulin-dependent) diabetic patients. METHODS: The five centres (Besançon, Geneva, Grenoble, Lyon, Strasbourg) of the GRAGIL network allow pancreas procurement, recipient recruitment, transplantation procedure and follow-up. Islet isolation is, however, performed in one single laboratory (Geneva). Pancreata were procured in each of the five centres and transported to Geneva with an ischaemia time of less than 8 hours. Islets were isolated using a standard automated method. If the islet number was too low for a graft (< 6,000 Islet-equivalent/kg), islets were cultured up to 12 days until another isolation was possible. Islets were transplanted by percutaneous transhepatic intraportal injection. Immunosuppression consisted of cyclosporine, mycophenolate mofetil, steroids and an anti-interleukin 2 receptor antibody. RESULTS: From March 1999 to June 2000, 56 pancreata procurements were performed with an average yield of 234500 islet-equivalent, with 32 preparations over 200000 islet-equivalent. Ten C-peptide negative Type I diabetic patients (5 men and 5 women, median age 44 years, median diabetes duration 29 years) with an established kidney graft (> 6 months) received 9,030 +/- 1,090 islet-equivalent/kg with a median purity of 63 %. The number of pancreata required for each graft was 1 (n = 5) or 2 (n = 5). At the completion of a 12 month follow-up, we observed 0% primary nonfunction, 50% graft survival and 20% insulin-independence. CONCLUSIONS/INTERPRETATION: This study demonstrates the interest and the feasibility of a multicentre collaboration in human islet transplantation.

Adult↗

Urinary F2-isoprostanes formation in kidney transplantation.

BACKGROUND: Oxygen free-radical mediated lipid peroxidation has been implicated in many diseases such as chronic renal failure, hemodialysis and chronic kidney transplant rejection. However, insight into the role of free radical generation in kidney transplantation has been constrained by the limitations of current indexes of oxidant stress in vivo. Isoprostaglandin F2alpha type-III (iPF2alpha-III, formerly known as 8-iso-prostaglandin F2alpha) is emerging as a reliable marker of oxidant stress in vivo. The purpose of our study was to investigate iPF2alpha-III formation as an index of lipid peroxidation in the 5 d following kidney transplantation. METHODS: Urinary iPF2alpha-III measurements were performed by enzyme immunoassay from day I to 5 in 11 patients undergoing kidney transplantation. Results were compared with 11 healthy volunteers matched in sex, age and cigarette smoking. RESULTS: Urinary excretion of iPF2alpha-III at day 1 did not significantly differ between control and transplant group (111 +/- 17 vs. 92 +/- 10 pM/ mM creatinine, respectively, NS). Urinary iPF2alpha-III levels did not differ between day 1 to 5, and were not correlated to cold ischaemia time. CONCLUSION: Our study shows no evidence of enhanced lipid peroxidation in the first 5 d following kidney transplantation.

Adult↗

[Management of oncocytoma in transplanted kidney].

The authors report a case of oncocytoma arising in a transplanted kidney. The diagnostic and therapeutic management is discussed and compared to the limited data reported in the literature on this subject. Immunosuppression of renal transplant recipients does not appear to increase the incidence of graft tumours, but, in the authors' opinion, modifies the conservative attitude generally proposed for this type of tumour.

Adenocarcinoma↗

Profiles and prognostic values of LDH isoenzymes in patients with non-Hodgkin's lymphoma.

Serum lactic dehydrogenase (LDH) is an important prognostic factor in patients with non-Hodgkin's lymphoma (NHL). We have examined the LDH isoenzyme content in serum and CSF of patients with NHL, at diagnosis and at relapse. In patients with increased serum LDH at diagnosis, the percentage of isoenzyme 2 was increased in 52% of patients and the absolute value of isoenzyme 3 was increased in 64% of patients. In relapsing patients these values were respectively 69% and 65%. Conversely in patients with increased serum LDH due to myeloid regeneration after chemotherapy, isoenzymes 4 and 5, but not isoenzymes 2 or 3, were increased. High absolute values of isoenzyme 3 were correlated with an altered performance status, advanced tumor stage, and aggressive histology whereas high isoenzyme 2 percentages were correlated with altered performance status only. Among patients with high total serum LDH, a high content of isoenzyme 2 and a high absolute value of isoenzyme 3 were correlated with high serum levels of TNFalpha and TNF receptor p75. Analysis of total LDH and LDH isoenzyme profiles in CSF did not reveal any correlation with meningeal involvement by lymphoma. High isoenzyme 2 percentages and high absolute values of isoenzyme 3 in serum were both significantly associated with a shorter freedom-from-progression and overall survival. Isoenzyme 3 remained a prognostic factor for survival even when considering only patients with high total serum LDH at diagnosis. We conclude that there are some characteristic serum LDH isoenzyme profiles in patients with NHL and that some of these specific alterations may help refine the prognostic value of total serum LDH.

Adolescent↗

[Economic contribution of mofetil mycofenolate as preventive immunosuppressive treatment after renal transplantation from cadaver].

OBJECTIVES: The economic impact resulting from the clinical consequences of immunosuppressive strategy using mycophenolate mofetil in new renal transplant recipients was conducted considering the viewpoint of the health insurance system. METHODS: The analysis was based on the results of three controlled randomized double-blind clinical trials comparing mycophenolate mofetil with placebo or azathioprine in 1003 out of 1493 included patients respectively. Health care costs associated with each event were determined by 7 French experts in renal transplantation working in six different hospitals. Direct cumulative costs for each strategy were compared. RESULTS: The studies demonstrated a difference in the incidence of acute rejection and treatment failures whatever the cause. The three trials showed that, compared with current strategies, use of mycophynolate mofetil in the immunosuppression protocol generated a 19 to 38% cost reduction during the 6 months after transplantation. Cost reduction resulted from lower incidence of acute rejection and the subsequent nephrectomics and dialysis sessions. The sensitivity analysis on the most important cost factors-cost of hospitalization per day and number of hospitalization days-confirmed strength of the results. CONCLUSION: Use of mycophenolate mofetil in the immunosuppressive prophylaxis protocol after renal transplantation allows a reduction in the direct costs during the 6 months following transplantation.

Adult↗