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Biomedical subjects

B Moulin

Publications and source records attributed to B Moulin.

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↗

Impact of cyclosporine reduction with MMF: a randomized trial in chronic allograft dysfunction. The 'reference' study.

Long-term use of calcineurine inhibitors (CNIs) may contribute to the development of chronic allograft dysfunction (CAD). We investigate the impact of the introduction of MMF combined with cyclosporine (CsA) 50% dose reduction. An open, randomized, controlled, multicenter, prospective study was conducted in 103 patients, receiving a CsA-based therapy with a serum creatinine between 1.7-3.4 mg/dL, more than 1 year after transplantation. They were randomized to receive MMF with half dose of CsA (MMF group) or to continue their maintenance CsA dose (control group). A total of 96 weeks after randomization, the evolution of renal function assessed by regression line analysis of 1/SeCr improved in the MMF group (positive slope) vs. the control group (negative slope), 4.2 x 10(-4) vs. -3.0 x 10(-4), respectively (p < 0.001). Concurrently, the absolute renal function improved significantly in the MMF group. No episode of biopsy-proven acute rejection occurred. One patient in each group lost his graft because of biopsy-proven chronic allograft nephropathy. There was a significant decrease of triglycerides level in the MMF group. Anemia and diarrhea were statistically more frequent in the MMF group. In CAD, the reduction of CsA in the presence of MMF results in significant improvement in renal function during a 2-year follow-up.

Adult↗

Post-transplant lymphoproliferative disorders occurring after renal transplantation in adults: report of 230 cases from the French Registry.

Post-transplant lymphoproliferative disorders (PTLD) are a rare but serious complication after organ transplantation. A French Registry of PTLD was set up in a nationwide population of kidney transplant recipients. We prospectively enrolled all adult kidney recipients developing PTLD between January 1, 1998, and December 31, 2003. We analyzed the incidence, risk and prognostic factors of PTLD by Kaplan-Meier and Cox analyses. Totally 230 cases of PTLD were referred to the French Registry. Cumulative incidence was 1.18% after 5 years. Older age (per year, AHR = 2.19, CI = 1.22-3.94) and recipient Epstein-Barr virus seronegativity (AHR = 3.01, CI = 1.57-5.08) were associated with an increased risk of PTLD. Patients with PTLD had a reduced survival rate (61% at 5 years). Graft PTLD had the best prognosis with an 81% survival rate after 5 years. Infection with hepatitis C or B virus (HCV or HBV), late-onset PTLD, multiple sites involvement and high Ann Arbor staging were risk factors for patient death. Use of azathioprine was associated with a poorer survival rate. PTLD incidence and risk factors in French recipients are in line with the international or American PTLD series. We highlighted the role of HBV or HCV in patient mortality and described the relevant prognosis factors for patients with post-transplant lymphoproliferations.

Adult↗

[Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in patients with solid organ transplantation: a clinical, neurophysiological and neuropathological study of 4 cases].

INTRODUCTION: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) rarely develops in patients with solid organ transplantation. PATIENTS AND METHOD: We describe the clinical, biological, electrophysiological and neuropathological features of 4 patients with solid organ transplantation who developed CIDP. Two patients had liver transplantation, one had kidney transplantation and one had lung transplantation. RESULTS: All 4 patients developed in the months following transplantation a syndrome that fulfilled criteria for definite CIDP. All patients had immunosuppressive therapy, with ciclosporin + prednisolone in 2 cases, tacrolimus in 1 case and azathioprine + prednisolone + ciclosporin in one case. One patient had chronic HCV and HBV infection. Treatment with intravenous immune globulin (IVIG) and/or a change in immunosuppressive therapy improved the neuropathy in all cases. CONCLUSION: CIDP is a rare and potentially treatable condition that should be considered in all patients with solid organ transplantation who develop a rapidly disabling sensorimotor polyneuropathy.

Humans↗

[Pharmacokinetics and dose adaptation of ofloxacine, pefloxacine and ciprofloxacine during haemodialysis and continuous ambulatory peritoneal dialysis].

Fluoroquinolones present various pharmacokinetic properties. That's the way we carried out a bibliographic summary about the pharmacokinetics of pefloxacin, ofloxacin and ciprofloxacin in patients hit by chronic renal failure, under haemodialysis or under continuous ambulatory peritoneal dialysis. Then, we will describe how to adapt drug dose according to the degree of renal insufficiency and the used molécule.

Anti-Infective Agents↗

[From the first symptoms to terminal renal failure: need for a nephrologic follow-up].

PURPOSE: As patients with chronic renal failure are frequently referred late to nephrologists, we decided to quantify the magnitude of late referral and its consequences. METHODS: We studied retrospectively an inception cohort of 62 patients starting dialysis (either hemodialysis or continuous ambulatory peritoneal dialysis) during 1993 with a 4-year follow-up. RESULTS: The mean delay between either first symptoms of renal disease, or first evidence of renal failure and nephrologist referral was 10 years and 3 years 56 days, respectively. About 47% of the patients were referred less than 6 months before starting dialysis, and 27.5% less than 1 month. Blood pressure levels were higher in patients referred less than 6, 3 and 1 month (P < 0.05), as was creatinine concentration in patients referred less than 1 month (P < 0.05). In contrast, plasma calcium was lower for referral less than 6 months (P < 0.05) and 3 months (P < 0.005), as was bicarbonate concentration for referral less than 3 and 1 month (P < 0.05). Initial hospitalisation stay was prolonged (x1.5) for late referral less than 3 months (56.4 +/- 39 days vs 35.9 +/- 33.6 days, P < 0.05) as was 6 months hospitalisation length for referral less than 3 months (x1.6) (52.9 +/- 40.6 days vs 33.2 +/- 28.7 days, P < 0.05) and less than 1 month (x1.8) (61 +/- 45 days vs 33.9 +/- 28.7 days, P < 0.05) and < 1 month (x1.8) (61 +/- 45 days vs 33.9 +/- 28.7 days, P < 0.05). Only 44.1% of patients started hemodialysis with a functioning arteriovenous fistula, and patients requiring temporary access had a 4.4-fold longer initial (60.1 +/- 41.7 days vs 13.6 +/- 11.6 days, P < 0.005) and 6-month (59.6 +/- 39 days vs 13.6 (9.1, P < 0.005) hospitalisation stay. The four-year mortality rate was unaffected by the delayed referral but strongly and independently predicted by age, diabetes and hypoalbuminemia. CONCLUSION: Early nephrologic referral and timely initiated dialysis decrease morbidity at the start of dialysis and both hospitalisation length and costs.

Adult↗

Compared ontogenesis of courtship song components of males from the sibling species, D. melanogaster and D. simulans.

The courtship song of Drosophila is known to be an important signal involved in sex and species recognition. It consists of pulse song and sine song, which have been studied in a quantitative way with different parameters. For the first time the setting of both components of the acoustic signaling is described and compared for males belonging to the sibling species D. melanogaster and D. simulans. At early ages, these two species share similar interpulse interval values but maturation establishes the species specificity of this character. For D. melanogaster the variations of several acoustic parameters take place in two successive periods, whereas for D. simulans the majority of the acoustic features does not change much with age. In D. melanogaster, copulation success seems to be linked to the maturation of the acoustic performance, which is not the case for D. simulans.

Age Factors↗

[Kidney and statins].

Patients with chronic renal diseases (CRD) have a high prevalence of lipid abnormalities. Elevated levels of total and low density lipoprotein cholesterol are associated with cardiovascular diseases in patients with CRD. The 3-hydroxy-methylglutaryl co-enzyme A reductase inhibitors appear to be the most effective agents to lower LDL cholesterol in this category of patients and are generally safe if used with caution. They should be drugs of first choice in CRD but dosage reduction and close monitoring may be required to avoid side effects in case of renal failure or in combination with calcineurin inhibitors. Moreover recent studies suggest that in addition to lowering plasma LDL cholesterol, theses compounds may modify several factors implicated in the development of atherosclerosis and the progression of chronic renal failure. Such newly defined effects may contribute to extend the use of statins in the management of renal patients.

Arteriosclerosis↗

Posttransplant lymphoproliferative disorders in renal allograft recipients: report of 53 cases of a French multicenter study. PTLD French Working Group.

New immunosuppressive therapies are currently being developed in renal transplantation and their relative risk in terms of posttransplant lymphoproliferative disorders (PTLD) must be carefully evaluated. For this purpose, a French registry of PTLD occurring after renal transplantation was set up. Among 10,000 patients presently followed up in 30 French renal transplantation centers, we prospectively identified 53 new PTLD (0.5%) since January 1998. Patients (34 male, 19 female) ranged from 3 to 72 years (mean age: 46 years), and the median time between grafting and diagnosis of PTLD was 63 months (2 months to 14 years). Ninety percent of recipients were Epstein-Barr virus (EBV) positive before transplantation. Most patients received a quadruple sequential therapy with polyclonal anti-lymphocyte globulin. Sites involved in PTLD were isolated lymph nodes in 13 cases, stomach or bowel in 10 cases, allograft in 14 cases, central nervous system in 6 cases, oropharynx in 4 cases, and skin or mucosa in 4 cases. Only three PTLD expressed markers of T lineage. Out of 40 studied tumors, 31 (78%) were EBV positive. Tumors were classified as polymorph in 26 cases and monomorph in 23 cases. Genotype studies in 18 PTLD showed a monoclonal pattern in 13 cases. In most patients, treatment consisted of reduction of immune suppression, 21 patients were given additional anti-viral therapy, 13 patients had anti-CD20, 23 patients underwent chemotherapy, and 4 patients were given cerebral radiotherapy. Five patients underwent transplantectomy. Sixteen patients (30%) died within the 1st year and 7 patients returned to dialysis (13%). The outcome of patients with PTLD remains poor, and the optimal approach to therapy is largely unknown. This ongoing registry is not only a national observatory but also a task force designed to improve the treatment strategy of PTLD.

Adolescent↗

Prediction of colloid osmotic pressure in renal patients.

BACKGROUND: Colloid osmotic pressure (COP) plays a major role in transcapillary fluid shift, including in the glomerular capillary. However, COP is generally estimated by quadratic equations derived from total plasma protein and/or albumin concentrations. The aim of this study was to assess the accuracy of such equations, and to determine the potential role of liver-derived non-albumin proteins in the maintenance of COP, especially in patients presenting a nephrotic syndrome. METHODS: COP was directly assessed with an osmometer in 170 patients (347 samples), and the results compared with calculated COP, using 4 previously published formulas [Brenner 1972, Canaan-Kühl 1993, Landis-Pappenheimer 1963, Navar 1977]. RESULTS: The 4 calculated COP values were strongly correlated with measured COP (range r = 0.88 - 0.96). However, in absolute terms, measured COP differed significantly from each of the 4 calculated mean values of COP (p < 0.001). Fibrinogen exerted per se a weak oncotic effect as measured in vitro. However, fibrinogen was highly related to albumin and presumably reflected the oncotic effect of other liver-derived non-albumin proteins. Inclusion of albumin and fibrinogen in a linear model provided an excellent fit for predicted COP with a highly significant correlation (r = 0.96, p < 0.001) over a wide range of COP values. The predicted equation was: COP(mmHg) = 6.89 x (albumin + fibrinogen) (g/dl) - 5.68. CONCLUSION: None of the 4 most commonly used formulas correctly predicted COP, and direct measurement of COP is still preferable for research studies. The introduction of fibrinogen into the formula estimating COP leads to higher accuracy, and therefore represents a more convenient model for routine evaluation.

Adolescent↗

Blood pressure, diabetes and diabetic nephropathy.

Despite multiple evidence-based data that diabetic nephropathy is largely preventable and its progression slowed by currently available interventions diabetic patients are often undertreated, especially for the lowering of blood pressure. Recent studies, (HOT Syst-Eur, SHEP, UKPDS, CAPPP, ABCD, HOPE) have confirmed the efficiency of intensively treated blood pressure in reducing morbidity-mortality in this group of patients at high risk. Low blood pressure targets are mandatory, but may not be that easy to achieve, especially in the presence of renal failure. Early prescription of a combination of antihypertensive drugs is often neccessary. Thus, the clinical question relates to the best combination of drugs. Most studies in hypertensive diabetic patients have dealt with 3 classes of antihypertensives drugs: diuretics, beta-blockers and ACE-inhibitors. Diuretics are one of the most efficient hypotensive drugs available for treatment of hypertension in diabetic patients. Their use must be encouraged early in the stepped approach since diabetes is usually associated with mid-volume expansion due to hyperinsulinism and hyperadrenergic state. In spite of the proven benefit of beta-blockers in diabetic patients, these drugs are largely underused. The indications for selective beta-blockers should probably be broadened for most diabetic patients in primary prevention. Beta-blockers are essential in secondary prevention for patients with coronary artery disease and hypertension. ACE-inhibitors are now more and more widely prescribed in diabetic patients at all stages of hypertension and nephropathy, but paradoxally their use has not been validated in Type 2 diabetic nephropathy. When the desired blood pressure target is obtained, cardiovascular outcome and probably also progression of diabetic nephropathy are significantly improved independently of a specific drug. Early combination therapy, including ACE-inhibitors, diuretics and beta-blockers, should be promptly proposed to all hypertensive diabetic patients to achieve low blood pressure and prevent high cardiovascular burden and progression of nephropathy.

Adrenergic beta-Antagonists↗

Comparison of cystatin C versus creatinine for detection of mild renal failure.

AIM: Serum cystatin C (SCyst) has been proposed as a novel indicator of GFR. PATIENTS AND METHODS: We compared SCyst, serum creatinine (SCreat) and Cockcroft and Gault's estimated clearance (CCG) using inulin clearance (Cin) as gold standard. 140 subjects (161 samples; aged 39 +/- 14; male/female: 79/82) underwent simultaneous measurements. RESULTS: A highly significant correlation r = 0.70, 0.74, 0.77 (p < 0.0001) was found between 1/SCyst, 1/SCreat, C(CG), respectively, and Cin. Receiver-operating characteristic (ROC) analysis was performed on SCyst, SCreat and C(CG) using a Cin cut-off of 90 ml/min/1.73 m2. Best fit for SCyst was 0.90 mg/l with a sensitivity of 75% and a specificity of 92%. The area under the ROC curve was not significantly greater for SCreat or C(CG) than for SCyst (p = 0.91,0.13, respectively). When relationship between Cin and SCyst was plotted, experimental data deviated from the theoretical model, suggesting that cystatin C may not be solely filtered. Additional patients were selected in our database on the basis of discordant SCreat/GFR values: false negative (n = 46 samples, 31 patients) and false positive (n = 16 samples, 9 patients). In this highly selected subgroup, 38% of the SCreat false positive had normal SCyst values and 48% of the false negative SCreat had abnormally elevated SCyst. CONCLUSION: This study suggests that SCyst is not more sensitive than SCreat or C(CG) for detecting renal failure, however, SCyst could be proposed as a confirmatory test for patients with elevated SCreat.

Adolescent↗