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Dominique Durand

Publications and source records attributed to Dominique Durand.

At least 37 records · Page 2Linked to original sources
PubMed2005

Follow-up of 28 HCMV seropositive renal-transplant recipients: comparison of clinical, biological and virological parameters in the groups of treated versus untreated infected patients.

BACKGROUND: A pre-emptive strategy for prevention of Human Cytomegalovirus (HCMV) disease depends on accurate detection of HCMV infection and clinical and/or biological abnormalities. OBJECTIVES: The aim of our study was to evaluate a therapeutic strategy based on the presence of either minimal clinical and/or biological symptoms or high HCMV viral load assessed by quantitative real-time PCR from whole blood as previously described. STUDY DESIGN: Between June 2002 and July 2003, 70 HCMV seropositive patients underwent a renal transplantation. Virological monitoring was performed every 2 weeks until day 90 then every 3-4 weeks until day 180. Biochemical and haematological parameters were also prospectively monitored. RESULTS: Twenty-eight patients (40%) showed at least one positive HCMV DNA in whole blood. Based on the following criteria: HCMV viral load greater than 4log(10)/ml, or the persistence of a HCMV DNAemia in two consecutive blood samples, or fever, or leucopenia or neutropenia, or increase in alanine aminotransferase level, 14 of the 28 patients received IV ganciclovir as a pre-emptive treatment. Immunosuppressive therapy and demographical data were comparable in both groups. As far as virological, haematological and biochemical parameters are concerned, no statistical significant difference was observed between treated and untreated patients. Moreover no adverse outcome was observed among untreated patients always having a HCMV viral load below 4log(10)/ml. CONCLUSIONS: This study reinforces the need of monitoring of HCMV seropositive renal-transplant recipients based on HCMV diagnosis and quantification by real-time PCR. The results showed that HCMV viraemic patients may benefit of absence of antiviral treatment when they have a low viral load (below 4log(10)/ml) and absence of clinical and/or biological abnormalities. Further studies are required now to validate the threshold value at which we should begin pre-emptive therapy.

Antibodies, Viral↗
PubMed2005

Acute hepatitis and renal function impairment related to infection by hepatitis E virus in a renal allograft recipient.

Clinicians often are faced with an increase in liver enzyme levels. In the majority of cases, the cause is found rapidly. Conversely, in a few cases, the etiologic agent remains unknown and requires either liver biopsy or drug-medication modification. We report a case of acute icteric hepatitis associated with renal function impairment related to infection caused by primary hepatitis E virus (HEV) in a renal transplant recipient who lived in a nonclassic endemic area and had not traveled abroad. Clinicians must be aware that in cases of unexplained hepatitis in organ transplant recipients and in the absence of evident drug hepatotoxicity, HEV should be considered as an etiologic agent for hepatitis. Subsequently, HEV serological tests should be performed, HEV RNA should be looked for in acute-phase serum and stool samples, and liver parameters should be monitored closely because HEV might be responsible, in some cases, for fulminant hepatitis.

Acute Disease↗
PubMed2005

Induction therapy with either anti-CD25 monoclonal antibodies or rabbit antithymocyte globulins in liver transplantation for hepatitis C.

BACKGROUND: Hepatitis C virus (HCV)-related end-stage liver disease (ESLD) is the leading cause for orthotopic liver transplantation (OLT). The aim of our sequential study was to assess the safety and efficacy of induction therapy using either rabbit antithymocyte globulins (RATG) or anti-CD25 monoclonal antibodies. METHODS: From January 2000 to January 2003, 31 patients underwent OLT for HCV-related ESLD, and survived more than 1 month post-transplantation. Up to July 2001, induction relied on RATG (Thymoglobulins; Sangstat, Lyon, France) which was given for a median of 5 d, i.e. a total dose of 406 +/- 45 mg (n = 16; group I). Thereafter, induction was based on either basiliximab or dacluzimab (n = 15; group II). Steroids and tacrolimus (from day 1 onwards) were given as maintenance therapy. The primary end-points were at 6 months post-transplantation. RESULTS: Patient and graft survivals were excellent and similar in both groups. The acute rejection rate was 37.5% in group I and 20% in group II (p = ns). The rates of serious bacterial and fungal infections as well as cytomegalovirus infections were similar in both groups. Even if the overall pattern of post-transplant liver enzymes did not differ between the two groups, the rate of HCV recurrence tended to be higher in group II (80%) compared with group I (56.25%; p = ns) patients. Both induction therapies were clinically and biologically well tolerated. CONCLUSION: RATG induction therapy is as efficient and as safe as induction with anti-CD25 monoclonal antibodies.

Adult↗
PubMed2005

Natural history of hepatitis C virus-related liver fibrosis after renal transplantation.

The aim of our study was to assess hepatitis C virus (HCV) evolution and long-term liver histology outcome in anti-HCV(+)/RNA(+) renal transplant (RT) patients. A total of 51 anti-HCV(+)/RNA(+) RT patients underwent liver biopsies (LB) every 3-4 years after transplantation (two LBs, n = 51; three LBs, n = 42; four LBs, n = 9). The hypervariable region (HVR)-1 of the HCV genome from all patients was characterized over time. Overall, the rate of liver fibrosis progression was 0.09 +/- 0.03 Metavir units/year. We identified three groups of patients: those in whom liver fibrosis remained stable (n = 21), those with progressing liver fibrosis (n = 21) and those with a regression in liver fibrosis (n = 10). In the last two groups, the progression and the regression of liver fibrosis were gradual during follow-up. Ferritin levels and hepatosiderosis were significantly higher in fibrosers. Initial fibrosis stage and high diversification of the HVR-1 of HCV genome between transplantation and the first liver biopsy were independent factors associated with liver fibrosis regression. In conclusion, in the current study, more than 10 years after renal transplantation, HCV infection was not harmful upon liver histology in more than 50% of patients. The diversification of the HVR-1 might be used to predict liver fibrosis outcome.

Adult↗
PubMed2004

Sequential protocols using basiliximab versus antithymocyte globulins in renal-transplant patients receiving mycophenolate mofetil and steroids.

BACKGROUND: Sequential anti-thymocyte globulins (ATG)/cyclosporine immunosuppression has two main advantages: delayed introduction of the nephrotoxic drug cyclosporine and prevention of acute rejection. Basiliximab, a recently developed chimeric monoclonal antibody that selectively depletes the minor subpopulation of activated T lymphocytes, has been shown to reduce the incidence of acute rejection when used with cyclosporine introduced on day 1. METHODS: This open, randomized, multicenter study was undertaken to compare the safety and efficacy of ATG versus basiliximab induction therapy (IT) with delayed introduction of cyclosporine for microemulsion (Neoral) in 105 low immunologic risk renal-transplant patients receiving mycophenolate mofetil and steroids. RESULTS: One-year patient and graft survival rates were 98.1% and 94.2%, respectively, in the basiliximab group (n = 52), and 98.1% and 96.2% in the ATG group (n = 53). The incidence of biopsy-confirmed acute rejection was comparable (basiliximab 9.6%, ATG 9.4%), as were key parameters of renal function, notably serum creatinine levels, time-to-nadir serum creatinine, and the number of patients requiring posttransplantation dialysis (basiliximab 28.8%, ATG 30.2%). However, significantly fewer patients in the basiliximab group experienced cytomegalovirus (CMV) infection, leukopenia, and thrombocytopenia, and this without any significant difference in any other key safety parameters (including the incidences of serum sickness, fever, lymphoma, and infections in general). CONCLUSIONS: Both ATG and basiliximab, when used for IT in a sequential protocol, are equally effective in terms of graft and patient survival as well as at preventing acute rejection. However, basiliximab is associated with a lower incidence of certain key adverse events, namely CMV infection, leukopenia, and thrombocytopenia.

Adolescent↗
PubMed2004

Villous atrophy induced by mycophenolate mofetil in renal-transplant patients.

Leucopenia and diarrhoea are the main side effects observed after the use of mycophenolate mofetil (MMF) in renal-transplant patients. The mechanism of diarrhoea remains unknown. We report on four cases presenting with severe diarrhoea, which appeared, respectively, at 4, 10, 24, and 66 months after MMF therapy had been started. All patients presented with weight loss and biological signs of malabsorption syndrome. Oesophago-gastroduodenoscopy revealed duodenal villous atrophy, which was confirmed by pathology examination. Anti-endomysium antibodies were negative. In all patients, diarrhoea disappeared within 1 month of MMF withdrawal without a gluten-free diet. A control oesophago-gastroduodenoscopy was performed in one patient 6 months later and was considered normal. None of the patients showed evidence of cytomegalovirus in enterocytes or cytomegalovirus-positive viraemia. In conclusion, villous atrophy induced by MMF might be one of the mechanisms of diarrhoea. It is mandatory to differentiate coeliac disease from MMF-induced villous atrophy because, in the latter case, a gluten-free diet is not required.

Adult↗
PubMed2004

Role of histone tails in the conformation and interactions of nucleosome core particles.

The goal of this work was to test the role of the histone tails in the emergence of attractive interactions between nucleosomes above a critical salt concentration that corresponds to the complete tail extension outside the nucleosome [Mangenot, S., et al (2002) Biophys. J. 82, 345-356; Mangenot, S., et al (2002) Eur. Phys. J. E 7, 221-231]. Small angle X-ray scattering experiments were performed in parallel with intact and trypsin tail-deleted nucleosomes with 146 +/- 3 bp DNA. We varied the monovalent salt concentration from 10 to 300 monovalent salt concentration and followed the evolution of (i) the second virial coefficient that characterizes the interactions between particles and (ii) the conformation of the particle. The attractive interactions do not emerge in the absence of the tails, which validates the proposed hypothesis.

Animals↗
PubMed2004

Influence of the ionic strength on the heat-induced aggregation of the globular protein beta-lactoglobulin at pH 7.

The influence of the ionic strength on the structure of beta-lactoglobulin aggregates formed after heating at pH 7 has been studied using static and dynamic light scattering. The native protein depletion has been monitored using size exclusion chromatography. Above a critical association concentration (CAC) well-defined clusters are formed containing about 100 monomers. The CAC increases with decreasing ionic strength. The so-called primary aggregates associate to form self similar semi-flexible aggregates with a large scale structure that is only weakly dependent on the ionic strength. The local density of the aggregates increases with increasing ionic strength. At a critical gel concentration, Cg, the size of the aggregates diverges. Cg decreases from 100 g/l without added salt to 1 g/l at 0.4M NaCl. For C > Cg the system gels except at high ionic strength close to Cg where the gels collapse under gravity and a precipitate is formed.

Hot Temperature↗
PubMed2004

Amantadine therapy in renal transplant patients with hepatitis C virus infection.

BACKGROUND: To date, there is no safe and efficient treatment of hepatitis C virus (HCV) infection after renal transplantation. Recently, there were encouraging reports after using amantadine in HCV-positive immunocompetent patients. OBJECTIVES: In an open pilot study, we evaluated the efficacy and the safety of amantadine monotherapy in 8 HCV positive renal-transplant patients with chronic active hepatitis and increased alanine aminotransferase (ALT) levels. RESULTS: After 6 months of amantadine therapy (200 mg per day), there were no decrease in HCV viremia (5.87 +/- 0.37 log copies/ml at M6 versus 5.71 +/- 0.5 log copies/ml at baseline; P > 0.05). However, we found a significant decrease in ALT activity (71 +/- 17 IU/l at M6 versus 100 +/- 9 IU/l at baseline; P = 0.04), whereas the decrease in aspartate aminotransferase activity did not reach statistical significance. There were no significant changes in liver histology. The clinical and biological tolerance was very good. Finally, there were a significant decrease in cyclosporine A whole blood trough levels during therapy. CONCLUSIONS: Our study is the first one to demonstrate that amantadine monotherapy lack of efficacy in HCV renal-transplant patients. It is able to improve liver enzymes but it has no impact neither upon HCV viremia nor upon liver histology.

Adult↗
PubMed2004

Effects of long-term lamivudine therapy in renal-transplant patients.

BACKGROUND: Following renal transplantation (RT), chronic immunosuppression is associated in hepatitis B virus (HBV) (+) patients with a flare-up of the disease, which might be harmful in the long term. OBJECTIVES: We report on the effect of long-term lamivudine therapy given at an initial daily dose of 100mg in 18 HBV (+) RT patients. RESULTS: When lamivudine therapy was commenced, 14 patients (77%) had an increase in their aspartate (AST) and alanine (ALT) aminotransferase levels. During a mean follow-up, under treatment, of 36.5 +/- 3.5 months (up to 66 months), 10 patients (55%) had a sustained partial (HBV DNA < 4 x 10(5)copies/ml) (n = 4) or complete (HBV DNA < 400 copies/ml) (n = 6) virological response. Overall, 12 virological breakthroughs were observed. Of those who were HBe Ag(+) prior to lamivudine therapy (n = 4), one seroconverted to HBe Ab during therapy. At the last follow-up, AST and ALT levels were normal in 13 patients. When liver biopsy was repeated during treatment (n = 15), the virological responders showed a significant decrease in total Knodell score from 10 +/- 0.6 to 7 +/- 1 (P = 0.04), but no significant change in the stage of fibrosis. Conversely, in those patients with high HBV DNA titers, there were no significant changes in the total Knodell score or in the grade of fibrosis. CONCLUSION: In conclusion, lamivudine therapy is safe in HBV(+)ve renal-transplant patients. However, even if the full and partial virological response rates are still high (55%) in the long term, relapse or primary non-responses occur. The implementation of alternative efficient strategies is warranted.

Antiviral Agents↗
PubMed2004

Regional citrate anticoagulation in continuous venovenous haemodiafiltration using commercial solutions.

BACKGROUND: Treatment with trisodium citrate provides an effective means of regional anticoagulation during continuous renal replacement therapy (CRRT). We evaluated the efficacy, safety and cost of a regional citrate anticoagulation protocol using commercial solutions in 17 critically ill patients treated with continuous venovenous haemodiafiltration (CVVHDF). We performed a total of 22 sessions. METHODS: We delivered an A.C.D-A(541(R)) solution containing 112.9 mmol/l disodium citrate (3.22%) at a median rate of 260 (190-280) ml/h via the pre-filter port of a COBE PRISMA with an AN-69 dialyser, while adjusting the rate to maintain post-filtered ionized calcium (iCa(2+)) between 0.25 and 0.4 mmol/l. Plasma iCa(2+) was maintained at >1.1 mmol/l by infusion of calcium chloride at a median rate of 1.70 (1.36-2.27) mmol/h. The dialysate was easily modified according to the acid-base status of each patient. Both replacement and dialysate solutions were delivered at 1200 ml/h. Each session was scheduled for 48 h and biological parameters were assessed every 6 h. RESULTS: The mean dialyser survival was 39 +/- 11 h (median 41.5 h; range 13-48 h). We observed dialyser clotting in four cases (18%). There were no bleeding events or modifications of coagulation parameters. The citrate solution, replacement solution and dialysate were obtained as commercial products. Both the replacement and dialysate solutions contained calcium. The extra cost of this technique was 25 euro;/day as compared to anticoagulation with heparin. CONCLUSIONS: We designed an efficient method of regional citrate anticoagulation for CVVHDF by using commercial solutions. The monitoring of patients was as intensive as during heparin anticoagulation for CRRT. Because of the higher cost of this method, it should be proposed only for patients with high bleeding risk.

Acute Kidney Injury↗
PubMed2004

Lower incidence of chronic allograft nephropathy at 1 year post-transplantation in patients treated with mycophenolate mofetil.

Chronic allograft nephropathy (CAN) is the main cause of graft failure after the first year of transplantation. This prospective, centrally randomized, open-label study was conducted to examine the possibility that mycophenolate mofetil (MMF) can prevent the emergence of CAN. The incidence of biopsy-proven CAN at 1 year was compared between two cyclosporine-based regimens comprising either mycophenolate mofetil (MMF) or azathioprine (AZA). The AZA group (n = 34) and the MMF group (n = 37) were balanced for all baseline characteristics of donors and recipients, the pre-existence of renal lesions on donor biopsy, the incidence of delayed graft function and acute rejection. Based on an intent-to-treat analysis, the number of patients with CAN at 1 year post-transplantation was significantly reduced in the MMF group (17/37-46%) compared with the AZA group (24/34-71%) (p = 0.03). When observed data were considered, 56/71 (78.8%) patients had a 1-year biopsy, and the number of patients with CAN was significantly lowered in the MMF group (9/29-31%) compared with the AZA group (17/27-63%) (p = 0.01). These results suggest a beneficial effect of MMF on the incidence of CAN at 1 year post-transplantation.

Adolescent↗
PubMed2003

Multivariate analysis of donor risk factors for graft survival in kidney transplantation.

BACKGROUND: The results of the transplantation of marginal donor kidneys remain controversial. This study aimed to investigate the impact of donor risk factors as predictors of kidney-graft outcome. METHODS: Allograft failure risk factors were studied in 7,209 cadaveric kidney-transplant recipients reporting to the Etablissement français des Greffes (EfG) from 1996 to 2000, of which 544 (7.6%) were from donors aged over 60. Both univariate and multivariate analysis were used to assess the effect of donor risk factors and were stratified according to recipient age. RESULTS: Overall graft survival was 91.1% (95% confidence interval [CI] 90.5-91.8) at 1 year, 88.6% (95% CI 87.8-89.4) at 2 years, and 85.6% (95% CI 84.6-86.6) at 3 years posttransplant. Univariate analysis of risk factors showed a significant reduction of graft survival in recipients transplanted with kidneys coming from donors older than 60 years, donors with a history of hypertension, a cerebrovascular cause of death, and a preharvesting serum creatinine greater than 150 micromol/L. Multivariate analysis revealed significantly higher failure rate associated with cerebrovascular cause of death (RR=1.2, P=0.02), history of hypertension (RR=1.2, P=0.04), and elevated serum creatinine (RR=1.3, P=0.03), whereas donor age greater than 60 years was not found as an independent risk factor. CONCLUSIONS: Our results suggest that cerebrovascular cause of death, history of hypertension, and elevated creatinine are significant independent donor risk factors for graft survival, whereas donor age is a statistically significant, but dependent, risk factor. This result is important for the design of allocation and transplantation strategies for kidneys procured in elderly donors.

Adolescent↗
PubMed2003

Evolution of hepatitis C virus quasispecies in renal transplant patients with de novo glomerulonephritis.

Long-term renal allograft survival in kidney transplant recipients infected by hepatitis C virus (HCV) may be influenced by the occurrence of de novo glomerulopathy associated with this virus. Therefore, we studied the evolution of HCV quasispecies in kidney transplant recipients infected by HCV with or without de novo glomerulopathy. The hypervariable region 1 (HVR-1) of the virus envelope was analyzed by cloning and sequencing 20 clones per sample to assess complexity and diversity from six kidney transplant patients who developed de novo glomerulopathy (group I) matched to six kidney transplant recipients without glomerular disease (group II), according to age, time since renal transplantation, and HCV genotype. Two sera were analyzed for each patient: one at the time of renal transplantation and the other at the time of appearance of de novo glomerulopathy, or after a similar duration since transplantation in group II. Overall, there was a significant increase of HCV viremia after the transplantation. This increase did not differ significantly between group I (+0.5 log copies/ml) and group II patients (+1 log copies/ml). The intersample diversity of HCV was similar in the two groups. Complexity and viral diversity were also similar at the time of transplantation. By contrast, complexity, diversity, and the proportion of nonsynonymous substitutions per nonsynonymous site were significantly higher after transplantation in group I patients. Our findings suggest a higher immune response and/or a particular cytokine production in patients developing de novo glomerulopathy rather than a direct effect of HCV on renal cells.

Adult↗
PubMed2003

Interaction between artificial membranes and enflurane, a general volatile anesthetic: DPPC-enflurane interaction.

The structural modifications of the dipalmitoylphosphatidylcholine (DPPC) organization induced by increasing concentration of the volatile anesthetic enflurane have been studied by differential scanning calorimetry, small-angle, and wide-angle x-ray scattering. The interaction of enflurane with DPPC depends on at least two factors: the enflurane-to-lipid concentration ratio and the initial organization of the lipids. At 25 degrees C (gel state), the penetration of enflurane within the lipids induces the apparition of two different mixed lipid phases. At low anesthetic-to-lipid molar ratio, the smectic distance increases whereas the direction of the chain tilt changes from a tilt toward next-neighbors to a tilt between next-neighbors creating a new gel phase called L(beta')(2NNN). At high ratio, the smectic distance is much smaller than for the pure L(beta') DPPC phase, i.e., 50 A compared to 65 A, the aliphatic chains are perpendicular to the membrane and the fusion temperature of the phase is 33 degrees C. The electron profile of this phase that has been called L(beta)(i), indicates that the lipids are fully interdigitated. At 45 degrees C (fluid state), a new melted phase, called L(alpha)(2), was found, in which the smectic distance decreased compared to the initial pure L(alpha)(1) DPPC phase. The thermotropic behavior of the mixed phases has also been characterized by simultaneous x-ray scattering and differential scanning calorimetry measurements using the Microcalix calorimeter of our own. Finally, titration curves of enflurane effect in the mixed lipidic phase has been obtained by using the fluorescent lipid probe Laurdan. Measurements as a function of temperature or at constant temperature, i.e., 25 degrees C and 45 degrees C give, for the maximal effect, an enflurane-to-lipid ratio (M/M), within the membrane, of 1 and 2 for the L(alpha)(2) and the L(beta)(i) lamellar phase respectively. All the results taken together allowed to draw a pseudo-binary phase diagram of enflurane-dipalmitoylphosphatidylcholine in excess water.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2003

X-ray diffraction characterization of the dense phases formed by nucleosome core particles.

Multiple dense phases of nucleosome core particles (NCPs) were formed in controlled ionic conditions (15-160 mM monovalent salt, no divalent ions), under osmotic pressures ranging from 4.7 x 10(5) to 2.35 x 10(6) Pa. We present here the x-ray diffraction analysis of these phases. In the lamello-columnar phase obtained at low salt concentration (<25 mM), NCPs stack into columns that align to form bilayers, kept separated from one another by a layer of solvent. NCPs form a monoclinic lattice in the plane of the bilayer. For high salt concentration (>50 mM), NCPs order into either a two-dimensional columnar hexagonal phase or into three-dimensional orthorhombic (quasi-hexagonal) crystals. The lamellar and hexagonal (or quasi-hexagonal) organizations coexist in the intermediate salt range; their demixing requires a long time. For an applied pressure P = 4.7 10(5) Pa, the calculated NCPs concentration ranges from approximately 280 to 320 mg/ml in the lamello-columnar phase to 495 to 585 mg/ml in the three-dimensional orthorhombic phase. These concentrations cover the concentration of the living cell.

Crystallization↗
PubMed2003

Long-term ribavirin therapy in hepatitis C virus-positive renal transplant patients: effects on renal function and liver histology.

BACKGROUND: Long-term renal transplant (RT) recipient mortality and graft loss increase significantly in hepatitis C virus positive (HCV-[+]ve) patients. Treatment with alpha-interferon in this population is associated with a high rate of acute rejection. The aims of this study were the evaluation of the efficacy and the safety of ribavirin monotherapy in 16 HCV-(+) RT patients (group A) matched to 32 HCV-(+) RT patients (group B) who did not receive ribavirin. METHODS: Ribavirin was started at a daily dose of 1,000 mg and then adapted to hemoglobin level. The study was scheduled for 1 year. RESULTS: Ribavirin monotherapy was associated with a decrease in liver enzymes and serum creatinine levels. When proteinuria was present, this decreased or disappeared. There were no significant changes in HCV viremia. There was a significant progression in liver fibrosis with no improvement in inflammation scores. Hemoglobin levels fall dramatically, despite an important support by recombinant erythropoeitin (median, 20,000 IU/wk). In 3 cases, ribavirin therapy had to be stopped. In the control group, after 1 year of follow-up, there was a significant increase in serum alanine aminotransferase and creatinine values. Proteinuria decreased in only 2 of 12 patients (P = 0.03 as compared with group A). CONCLUSION: One year of ribavirin monotherapy seems to have, at best, no beneficial effect on liver histology, although it improves liver enzyme levels. Despite its efficiency to dramatically decrease proteinuria, its impact on renal function remains unknown.

Adult↗