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C Legendre

Publications and source records attributed to C Legendre.

At least 19 recordsLinked to original sources
PubMed2000

Development of cytomegalovirus resistance to ganciclovir after oral maintenance treatment in a renal transplant recipient.

The emergence of a resistant strain is a theoretical threat after extensive use of antiviral drugs. We report the emergence of a ganciclovir-resistant cytomegalovirus (CMV) strain in a kidney transplant recipient during oral ganciclovir maintenance treatment. The patient was treated by oral ganciclovir for 2 months after successful treatment of CMV primary infection by intravenous ganciclovir. He developed a new episode of CMV infection with no clinical response to intravenous ganciclovir. The CMV isolate exhibited both phenotypic and genotypic resistance to ganciclovir. The CMV isolate was constituted of a mixture of strains, with and without a mutation at codon 460 of the UL97 gene. The clinical condition improved when mycophenolate mofetil (MMF) was discontinued, and a short course of intravenous globulin was added to ganciclovir. The emergence of the CMV strain could be secondary to more potent immunosuppression provide by MMF or subtherapeutic level obtained during oral ganciclovir treatment. We believe that ganciclovir resistance must be part of the differential diagnosis when a patient relapses or fails to respond to ganciclovir treatment.

Administration, Oral↗
PubMed1999

Human herpes virus-8 and other risk factors for Kaposi's sarcoma in kidney transplant recipients. Groupe Cooperatif de Transplantation d' Ile de France (GCIF).

BACKGROUND: The exact reasons for the high incidence of Kaposi's sarcoma (KS) after kidney transplantation are still unknown. Immunosuppression is classically considered as the main risk factor, but the relative risk contributed by the patient's geographic origin and by human herpes virus (HHV)-8 infection still has to be determined. METHODS: We carried out a retrospective and a prospective study among kidney transplant recipients (TP) to identify the risk factors for posttransplantation KS. Each of 30 KS patients was matched with two controls to investigate the association with geographic origin, immunosuppressive regimen, HHV-8 antibodies before and after transplantation, and other infections. Among TP with new onset of KS, we prospectively evaluated HHV-8 serology and viremia in response to decreased immunosuppression. RESULTS: African and Middle East origins, past infection with hepatitis B, hemoglobin level <12 g/dl, lymphocyte count <750/mm3 at the time of diagnosis and initial use of polyclonal antilymphocyte sera were risk factors for KS. After multivariate analysis, origin in Africa or Middle East and use of antilymphocyte sera for induction remained as independent risk factors. Sixty-eight percent (17/25) of TP with HHV-8 antibodies before or after transplantation developed KS compared with 3% (1/33) of seronegative TP (P<0.00001). HHV-8 DNA was detectable in seven of nine peripheral blood mononuclear cells (PBMC) and in six of six KS lesions at diagnosis; it became negative in PBMC in three of five patients in parallel with tumor regression. CONCLUSION: African and Middle East geographic origins, HHV-8 infection before and after kidney transplantation, and initial use of polyclonal antilymphocyte sera were independent risk factors for KS. The presence of HHV-8 antibodies before or after transplantation was highly predictive of the emergence of posttransplantation KS and conferred a 28-fold increased risk of KS (odds ratio=28.4; 95% confidence interval: 4.9-279). Detection of HHV-8 DNA within PBMC and KS lesions seems related to tumor burden and evolution.

Adult↗
PubMed1999

[Kidney transplantation and pregnancy].

Genetically active women suffering from chronic renal failure must have kidney transplantation to carry one or more pregnancies to term. Such pregnancies must be considered as high-risk pregnancies requiring multidisciplinary surveillance. The role of the transplanting physician is to explain to these patients the risk of pregnancy for the graft and also to help them plan their pregnancy at the optimal moment. The role of the gynecologist is mainly to optimize fetal surveillance and limit the risk of hypotrophy. The current high quality of this collaboration has made it possible to achieve excellent results for the mother and the child. We present recent epidemiological data on the consequences of kidney transplantation on pregnancy, the consequences of pregnancy on the renal graft and also on the modalities of the necessary multidisciplinary follow-up.

Abortion, Spontaneous↗
PubMed1999

Changes in plasma cystatin C after renal transplantation and acute rejection in adults.

BACKGROUND: Cystatin C has recently been proposed as an alternative marker of glomerular filtration rate. The diagnostic value of plasma cystatin C for the longitudinal assessment of kidney function after renal transplantation, however, has not been addressed. METHODS: Renal function was evaluated in 30 adults receiving renal transplants (46 +/- 9 years, mean +/- SD) and in 56 healthy controls (38 +/- 10 years) using cystatin C. Plasma cystatin C was determined daily starting the day of surgery and for 3 weeks after surgery by an immunonephelometric assay. RESULTS: Plasma concentration significantly decreased during the first week (-44% vs -29% for creatinine). Plasma cystatin C correlated with plasma creatinine (r = 0.741; P <0.0001) and the reciprocal of the creatinine clearance estimated by the Cockcroft-Gault formula (r = 0.882; P <0.001). In all three cases of acute renal impairment, the increase in plasma cystatin C values was more prominent than that of creatinine. CONCLUSIONS: Plasma cystatin C is an alternative and accurate marker of allograft function in adult transplant patients. Increased sensitivity compared with creatinine for the detection of acute reduction in glomerular filtration rate allows in some cases a more rapid diagnosis of acute rejection or treatment nephrotoxicity.

Adult↗
PubMed1998

Peroxisome proliferator-activated receptor alpha-isoform deficiency leads to progressive dyslipidemia with sexually dimorphic obesity and steatosis.

The alpha-isoform of the peroxisome proliferator-activated receptor (PPARalpha) is a nuclear transcription factor activated by structurally diverse chemicals referred to as peroxisome proliferators. Activators can be endogenous molecules (fatty acids/steroids) or xenobiotics (fibrate lipid-lowering drugs). Upon pharmacological activation, PPARalpha modulates target genes encoding lipid metabolism enzymes, lipid transporters, or apolipoproteins, suggesting a role in lipid homeostasis. Transgenic mice deficient in PPARalpha were shown to lack hepatic peroxisomal proliferation and have an impaired expression and induction of several hepatic target genes. Young adult males show hypercholesterolemia but normal triglycerides. Using a long term experimental set up, we identified these mice as a model of monogenic, spontaneous, late onset obesity with stable caloric intake and a marked sexual dimorphism. Serum triglycerides, elevated in aged animals, are higher in females that develop a more pronounced obesity than males. The latter show a marked and original centrilobular-restricted steatosis and a delayed occurrence of obesity. Fat cells from their liver express substantial levels of PPARgamma2 transcripts when compared with lean cells. These studies demonstrate, in rodents, the involvement of PPARalpha nuclear receptor in lipid homeostasis, with a sexually dimorphic control of circulating lipids, fat storage, and obesity. Characterization of this pathological link may help to delineate new molecular targets for therapeutic intervention and could lead to new insights into the etiology and heritability of mammalian obesity.

Animals↗
PubMed1998

Long-term outcome of kidney transplantation in patients with systemic lupus erythematosus: a multicenter study. Groupe Cooperatif de Transplantation d'île de France.

BACKGROUND: The outcome of 60 renal transplantations in 53 patients with end-stage renal disease (ESRD) because of lupus nephritis was studied retrospectively and compared with 106 controls matched for age, sex, maximum panel-reactive antibody (PRA) level, and date of transplantation. METHODS: The patients received their transplants over a 260-month period (21.5 years) between October 1971 and August 1993. The population was predominantly women (90%), and the mean age at the time of the transplantation was 33.2 years (range: 21-54 years). Fifty-six transplants (93%) were from cadaveric donors, and 4 (7%) were from living-related donors; 46 patients (86%) had primary allografts, and 7 (14%) received a second allograft. The duration of disease before transplantation was 93.6+/-6.2 months, and the duration of dialysis before transplantation was 48+/-6 months. RESULTS: No patient had clinically active systemic lupus erythematosus (SLE) at the time of transplantation. The 1-year graft and patient survival rates were 83% and 98%, and the 5-year graft and patient survival rates were 69% and 96%. Actuarial graft and patient survival rates in SLE patients were not significantly different from those of the matched control group. Chronic rejection was the major risk factor for graft loss. Lupus nephritis recurred in the graft of one patient 3 months after transplantation, and there were extrarenal manifestations of SLE in four others. CONCLUSIONS: The present study confirms that patients with SLE can receive transplants with excellent graft and patient survival rates and a low rate of clinical recurrent lupus nephritis.

Adult↗
PubMed1998

Fenofibrate modifies transaminase gene expression via a peroxisome proliferator activated receptor alpha-dependent pathway.

Fibrates modify the expression of genes implicated in lipoprotein and fatty acid metabolism via the peroxisome proliferator-activated receptor alpha(PPARalpha), leading to reductions in serum triglycerides and cholesterol. The expression of certain genes regulated by PPARalpha have been shown to be modified in a species dependent manner. Aspartate aminotransferase (AspAT or GOT) and alanine aminotransferase (AlaAT or GPT) are enzymes involved in intermediate metabolism in all cells and in hepatic gluconeogenesis. These enzymes are also widely used as serum markers of possible tissue damage. This study investigated whether fenofibrate could modify the expression of liver AspAT and/or AlaAT and thus possibly alter transaminase levels independently of a cytotoxic effect. In human Hep G2 cells, fenofibrate increased cytosolic AspAT (cAspAT) activity by 40% and AlaAT activity by 100%, as well as both mRNAs. Nuclear run on assays showed that this effect was, at least in part, transcriptional. Increases in mRNA were also observed in human hepatocyte cultures at concentrations of the drug attained in patients. In C57BL/6 mice, fenofibrate decreased cAspAT and cAlaAT mRNA, while these effects were abolished in PPARalpha knock-out mice. In conclusion, fenofibrate has been shown to modify cAspAT and AlaAT gene expression in a species and PPARalpha dependent manner. This is the first demonstration that cAspAT and AlaAT activities may be pharmacologically altered, independently of a toxic phenomenon.

Alanine Transaminase↗
PubMed1998

B cell-driven HIV type 1 expression in T cells: an essential role of CD86 costimulatory molecule.

During HIV-1 infection, HIV-1 is sequestered and actively replicates within lymphoid organs, mainly in areas essential for antigen-specific T-B interactions. We investigated whether cognate T-B interactions not only drive humoral response to HIV-1 but also enhance viral replication. Costimulation of in vitro HIV-1-infected tonsillar T cells with autologous or allogeneic activated B cells increased both viral replication and T cell proliferation. Addition of CD86 MAb to cocultures inhibited most p24 (84 +/- 12%, n = 13) and IL-2 (99 +/- 2%, n = 6) production, decreased T cell proliferation by 46 +/- 15% (n = 13), and decreased TNF-alpha and IFN-gamma production by 67 +/- 17% (n = 6) and 53 +/- 6% (n = 6), respectively. In contrast, CD80 MAb, which strongly inhibited IL-2 production (77 +/- 10%, n = 6), moderately downregulated p24 and TNF-alpha production (29 +/- 21%, n = 13 and 34 +/- 10%, n = 6, respectively) and did not decrease T cell proliferation (8 +/- 10%, n = 13) or IFN-gamma production (14 +/- 13%, n = 6). We thus showed that B cells deliver a potent CD86/CD28 costimulatory signal that induces T cell proliferation and simultaneously enhances HIV-1 replication. CD86+ B cells, mainly localized within the light zone of germinal centers, might thus favor active in situ replication of HIV-1 in response to each new challenge by T-dependent antigens.

Antigens, CD↗
PubMed1998

Histologic features of chronic allograft nephropathy revealed by protocol biopsies in kidney transplant recipients.

BACKGROUND: The aim of the present study was to describe the histologic features disclosed by protocol kidney transplant biopsies in patients who experienced neither acute rejection nor acute renal failure during the 2 years after transplantation. METHODS: We studied 10 recipients of HLA-identical kidneys from living-related donors and 31 recipients of cadaveric kidneys. They were selected because, during the 2 years after transplantation, they did not experience clinical acute or chronic rejection, their renal function was normal and stable, and they underwent a protocol kidney biopsy at 3 months and at 2 years after transplantation. RESULTS: Histologic chronic allograft nephropathy was present in 25% of patients at 3 months and in 50% at 2 years, but was absent in the recipients of HLA-identical kidneys. Histologic worsening was associated with increased donor age, the presence of asymptomatic grade I acute rejection at 3 months, and an increased cyclosporine trough level. CONCLUSIONS: Protocol biopsies contribute important information that could be used to improve the prophylaxis of chronic allograft nephropathy.

Adult↗
PubMed1998

Harmful long-term impact of hepatitis C virus infection in kidney transplant recipients.

BACKGROUND: The long-term impact of hepatitis C virus (HCV) infection in renal transplant recipients remains controversial. We report here our experience, in a homogeneous single center, of 499 patients with a fairly long follow-up. METHODS: We retrospectively studied 499 hepatitis B virus-negative patients who received an initial cadaver donor kidney transplantation at Necker Hospital between January 1, 1979 and December 31, 1994, with a graft or patient survival of at least 6 months. Anti-HCV antibodies were detected at time of transplantation in 112 patients (22%). Patient survival and causes of death were compared among anti-HCV-positive and -negative patients RESULTS: Our results clearly indicate that first cadaver kidney transplant recipients with anti-HCV antibodies had a significantly shorter patient and graft long-term survival than recipients without anti-HCV antibodies (P<0.01 and P<0.0001 respectively). Mean follow-up time after transplantation was 79+/-2 months in the former group and 81+/-5 months in the latter (NS). Increased mortality was primarily caused by liver disease (P<0.001) and sepsis (P<0.01). In a multivariate analysis, HCV infection significantly affected the mortality rate (odds ratio: 2.8). CONCLUSIONS: These results suggest that HCV infection has a harmful long-term impact on the survival of kidney transplant recipients.

Adult↗