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P Berthoux

Publications and source records attributed to P Berthoux.

At least 19 recordsLinked to original sources
PubMed2007

TNFA2 and d2 alleles of the tumor necrosis factor alpha gene polymorphism are associated with onset/occurrence of idiopathic membranous nephropathy.

Idiopathic membranous nephropathy (IMN) has a strong association with the major histocompatibility complex HLA B8DR3(17)DQ2 haplotype. The tumor necrosis factor (TNF)A gene is located within the major histocompatibility complex region on chromosome 6. We have studied the influence of two functional polymorphisms; the -308 (promoter region) and the TNFd microsatellites on initiation and/or progression of IMN. This was a case-control study comparing data from 100 Caucasians patients (67 male subjects; 67%) with IMN to 232 Caucasians local controls (171 male subjects; 74%). We have analyzed genotypes and alleles distributions and the role of these polymorphisms in disease progression towards end-stage renal failure or patient death. For -308 TNFA polymorphism, distribution of genotypes was significantly different between IMN and controls (chi(2)=16.25; P=0.0003): the A2 allele frequency was 28.0% in IMN vs 15.3% in controls (chi(2)=14.57; P=0.0001). For TNFd polymorphism, alleles distribution (from d1 to d7) was also significantly different between IMN and controls (chi(2)=56.74; P<0.0001) with both diminished d3 allele frequency (chi(2)=27.30; P<0.0001; Pc=0.001) and increased d2 allele frequency (chi(2)=29.95; P<0.0001; Pc=0.001) in IMN. We could not isolate any significant and independent influence of these different genotypes on IMN disease progression. The TNFA2 and TNFd2 alleles were strongly associated with occurrence/initiation of IMN and should be considered as susceptibility genes for this disease.

Adult↗
PubMed2006

CC-chemokine receptor five gene polymorphism in primary IgA nephropathy: the 32 bp deletion allele is associated with late progression to end-stage renal failure with dialysis.

The chemokine (CK) receptor 5 (CCR5) is necessary for two adjacent cysteines (CC)-CKs such as Regulated upon Activation Normal T cell Expressed and Secreted, a/o Macrophage Inflammatory Protein 1alpha/beta to mediate their inflammatory properties. The CCR5 gene polymorphism with 32-basepair deletion (d32) leads to receptor inactivation/dysfunction in homo/heterozygous individuals. We have evaluated its role in both initiation and/or progression of primary immunoglobulin A (IgA) nephropathy (IGAN) in a case-control study involving a prospective cohort of 318 IGAN patients and a matched group of 294 controls. Genotyping was performed by a two-specific primers single polymerase chain reaction technique: normal allele (nl) vs d32 allele. The d32 allele frequency was not different in patients (11.0%) vs controls (8.3%), indicating no significant influence on IGAN initiation. Genotype to clinical phenotype correlation demonstrated that progression to renal/patient death was associated with the d32 allele: 18.2% (12 out of 66 with d32) vs 8.3% (21 out of 252); chi(2)=6.73; P=0.017. The Kaplan-Meier survival without renal/patient death was worse in d32-positive patients (log-rank test; P=0.002). The Cox regression analyses confirmed that the nl/nl genotype was a significant and independent protective factor for progression to end-stage renal failure (ESRF)/dialysis: beta/standard error (s.e.)=-3.1; chi(2)=9.5; relative risk=0.31 (95% confidence interval 0.15-0.65); P=0.002. The d32-CCR5 polymorphism played a significant role in the progression of primary IGAN, with the nl/nl genotype being an independent protective factor for late progression towards ESRF/dialysis. These data raise question about the usefulness of systematic CCR5 genotyping in IGAN patients.

Adult↗
PubMed2002

Hypertension after renal transplantation and polymorphism of genes involved in essential hypertension: ACE, AGT, AT1 R and ecNOS.

BACKGROUND: Arterial hypertension (HT), secondary to cyclosporine A (CsA) used as main immunosuppressive treatment in renal transplantation (RTx), is very frequent (70%), usually severe and explained mostly by vasoconstriction of the glomerular afferent arteriole with secondary sodium and water retention. MATERIAL AND METHODS: In a retrospective study, we have analyzed 294 consecutive recipients receiving a first renal cadaveric allograft and all treated with CsA (the majority with triple therapy). We studied, by molecular biology, the polymorphism of genes previously implicated in essential HT such as: angiotensin-converting enzyme (ACE: II, ID and DD), angiotensinogen (AGT: MM, MT and TT), angiotensin II type 1 receptor (AT1-R: AA, AC and CC) and endothelial constitutive nitric oxide synthase (ecNOS: aa, ab and bb), and correlated the data to the prevalence and severity of post-Tx HT. This cohort included 195 (66%) males and 99 females with a mean age of 42 years at time of Tx. The presence and severity of post-Tx HT were indicated by initial persistent blood pressure over 140/90 mmHg with the need for at least one anti-hypertensive drug and by the number of anti-HT medications required to achieve its control. RESULTS: The distribution of the specific alleles and genotypes for ACE, AGT, AT1-R, and ecNOS was not different in transplant recipients compared to 181 controls. At 5 years post-Tx, the prevalence of HT was 72% (169 out of 235) among functioning grafts. There was no significant difference for ACE, AGT, AT1R and ecNOS genotypes distribution between hypertensive vs non-HT recipients. The number of anti-hypertensive drugs prescribed was not different among ACE, AGT, and AT1-R genotypes. However, the a allele and the non-bb genotype (aa + ab) for ecNOS were significantly (p = 0.001) associated with a less severe HT, needing fewer anti-HT drugs. At 10 years post-Tx, the HT prevalence remained high 78% (67 out of 86) among functioning Tx. However, the limited numbers did not allow further correlation. CONCLUSIONS: This study produced mainly negative results except for ecNOS-a allele, which seems to protect against severe hypertension. The explanation remains speculative but probably relates to the known cyclosporine-induced upregulation of ecNOS gene and enzyme activity.

Adolescent↗
PubMed2001

Comparison of ELISA method versus MEIA method for daily practice in the therapeutic monitoring of tacrolimus.

BACKGROUND: For the adequate management of transplant patients on tacrolimus therapy, it is important to obtain optimal blood concentrations. The purpose of this study was to determine the most appropriate method for daily practice of tacrolimus determination in whole blood. We compared enzyme-linked immunosorbent assay (ELISA) with microparticle enzyme immunoassay (MEIA), using European controls and blood samples from organ graft recipients treated with tacrolimus. Time, practicability and cost were considered also. METHODS: The assays were performed according to the procedures detailed in the product inserts. In five European controls and 40 blood samples from kidney and liver transplant patients, we determined the blood levels of tacrolimus by both MEIA and ELISA tests. RESULTS: MEIA gave more reliable results with the European controls (y=1.078x+0.092; r=0.996) than ELISA (y=0.956x+1.307; r=0.946). For the patient samples, the correlation between the two tests was 0.85 and the extreme range of values was +65% and -56% for ELISA vs MEIA. Although the manufacturer of the ELISA test used claims the best sensitivity and precision, in our experience the MEIA test was quicker and cheaper. CONCLUSIONS: MEIA provides a quick, reliable and easy-to-handle method for routine monitoring of tacrolimus blood levels.

Enzyme-Linked Immunosorbent Assay↗
PubMed1999

[Update on hepatitis G virus].

HEPATITIS G VIRUS: The hepatitis G virus is an RNA virus with a genomic organization and variability similar to the hepatitis C virus but with a much different pathogenic power which remains to be elucidated. HEPATITIS G: No cases of chronic hepatitis have been observed. Coinfections with HCV and HIV do occur but do not aggravate the prognosis. Anti E2 antibodies are found in the serum and correspond to elimination and neutralization of the HVG genome. There is a high prevalence in transplant recipients (31%), but no modification in liver or kidney grafts has been reported.

Flaviviridae↗
PubMed1999

Membranoproliferative glomerulonephritis with subendothelial deposits (type 1) associated with hepatitis G virus infection in a renal transplant recipient.

BACKGROUND: Infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) is a well-known etiology for membranoproliferative glomerulonephritis (MPGN) with subendothelial deposits (MPGN type 1). MATERIAL AND METHODS: The newly discovered hepatitis G virus (HGV) is currently under active investigation. We report the first case of de novo MPGN type 1 associated with HGV infection in a young male renal transplant recipient who manifested glomerulonephritis (GN) with proteinuria 7 years after transplant, and whose original disease was chronic obstructive pyelonephritis secondary to nephrolithiasis. RESULTS: Serum markers for HBV and HCV infections were negative. HGV infection was detected by specific double-nested reverse transcriptase-polymerase chain reaction (RT-PCR) in sera (positive HGV viremia) 2.5 years after renal transplantation. By specific in situ RT-PCR, the presence of the HGV genome was detected in peripheral blood mononuclear cells and in the kidney biopsy (glomeruli and tubules), but not in the liver. CONCLUSION: This report adds new information on the role of HGV infection in the occurrence of de novo GN (MPGN type 1) in renal transplantation.

Adult↗
PubMed1998

High prevalence of hepatitis G virus (HGV) infection in renal transplantation.

INTRODUCTION: The newly discovered (1995) hepatitis G virus (HGV) is an RNA virus from the Flaviviridae family with 85% genomic homology to GB virus C (GBV-C). We studied the prevalence of HGV infection among a cohort of 398 renal transplant recipients (RTR), all of whom had previously received blood transfusions, been grafted between August 1984 and December 1991, and been treated by cyclosporin A (CsA) as the main immunosuppressant. SUBJECTS AND METHODS: According to hepatitis C virus (HCV) antibody status, and after exclusion of 28 HBs antigen-positive recipients, this cohort had previously been divided into an HCV +ve subgroup (106 RTR; 62 M vs 44 F; 29 French vs 77 non-French) and an HCV -ve subgroup (264 RTR; 181 M vs 83 F, 196 French vs 68 non-French). We randomly selected 27 RTR in the HCV+/HBV- subgroup (14 M vs 13 F, 10 French vs 17 Italians) and 27 RTR in the HCV-/HBV- subgroup (19 M vs 8 F, 18 French vs 9 Italians) for HGV screening. The detection of HGV RNA sequences in serum (viraemia) was done by double nested RT-PCR using specific primers chosen in the 5' non-coding genomic region. The serum detection of specific antibodies (anti E2) was done by ELISA test. All sera (at time of liver biopsy or at last follow-up) were tested in duplicate. RESULTS: The prevalence of HGV viraemia was 26% (14/54) in the whole group and in both HCV +ve and -ve subgroups (7/27). The prevalence of HGV infection (viraemia + and/or anti E2 antibodies +) was 44% (24/54) in the whole group and in both HCV +ve and -ve subgroups (12/27). In addition, the prevalence was similar in males vs females and in French vs foreigners recipients (mostly Italians). In the HCV +ve subgroup, the seven HGV viraemia-positive patients who previously had liver biopsies disclosed chronic active hepatitis in four (mean Knodell score 5.75) and normal livers in three, with only one case of elevated ALT (CAH 5). In the HCV- subgroup, none of the seven HGV+ viraemic patients had elevated ALT and liver biopsy was not performed. CONCLUSION: HGV infection prevalence is high (44%) in RTR, but clearly independent of HCV status and/or the geographical origin of the recipients. This data indicates a different epidemiology as compared to our HCVs previous experience.

Adult↗
PubMed1996

Role of oral contraceptives in the growth of a multilobular adenoma associated with a hepatocellular carcinoma in a young woman.

BACKGROUND: The occurrence of hepatocellular neoplasms is frequently reported in young females. The role of oral contraceptives in the development of these tumors is considered. METHODS: A 14-cm tumor was diagnosed in a 24-year-old female who had been taking the contraceptive pill for the last 3 years. Numerous blocks of this lesion were histologically and immunohistochemically analyzed. Some fragments of the lesion were snap-frozen in order to search for sex hormonal receptors and hepatitis B and C virus. RESULTS: On histological examination, the tumor was found to be a hepatocellular, multilobular adenoma with small foci of hepatocellular carcinoma. Neither hepatitis B virus nor hepatitis C virus was found in serum or in the tumor. Nuclear estrogen receptors and progesterone receptors were detected by immunohistochemical analysis in both the adenoma and the carcinoma, but only progesterone receptors were detected by a radio-ligand binding assay in the tumor. CONCLUSION: This finding suggests that the contraceptive pill may stimulate the growth of hepatocellular, multilobular adenomas through the binding of hormonal compounds to their specific receptors within tumoral cells.

Adenoma, Liver Cell↗
PubMed1996

HCV liver disease in renal transplantation: a clinical and histological study.

The prevalence of HCV infection is high in renal transplantation (RT) patients: 29% in our cohort of 399 RT recipients. The consequences of that infection on the liver have to be carefully assessed. Clinical chronic hepatitis was detected from ALT concentrations (> x 1.5 N) in only 26 patients (22%) with constant (15%) or fluctuating (85%) ALT elevation. Only three of 117 cases developed cirrhosis (3%). No liver cancer was noted. Liver biopsy was performed (mean interval = 60.2 months) in 62 patients with HCV infection alone. We found 26 cases (42%) of chronic active hepatitis (CAH) with a mean Knodell score as low as 6.1 (range: 3-12), a mean activity grade of 4.9, and a fibrosis stage of 1.3. Twelve patients (19%) presented with normal liver pathology and met the criteria of healthy HCV carriers (positive viraemia, normal ALT and normal liver). The rest presented with portal lesions, either inflammation or fibrosis. In addition, patient and graft survival rates did not differ in HCV+ recipients. To conclude, HCV infection did not appear too deleterious for the liver in this cohort of patients. There is therefore no contraindication for HCV-positive recipients to undergo renal transplantation.

Adolescent↗
PubMed1996

Glomerular disease during HCV infection in renal transplantation.

In general nephrology, HCV infection has been associated with type I membranoproliferative glomerulonephritis (MPGN type I) associated with cryoglobulinaemia. In a cohort of 399 renal transplantation (RT) recipients, 117 of whom (29%) were HCV-positive, we selected all patients diagnosed as having membranous GN or type I MPGN by graft biopsy. The prevalence of MGN was 16/399 (4%) with three recurrences, and 13 de novo cases. Only 5/16 (31%) were HCV+, not different from the general RT population. Five patients had an outcome of graft failure after 43 months. Conversely, there were 15 cases of type I MPGN (two recurrences, 13 de novo) but with eight HCV+ recipients (53%, P = 0.02). Considering only the French patients, prevalence was 44% vs 12% in the French RT population (P = 0.006). Eight patients had graft rejection after 59 months (five HCV+). In this type I MPGN subgroup, there were two positive cryoglobulins, two rheumatoid factors and four hypocomplementaemias. In conclusion, there is a clear association between HCV infection and the occurrence of type I MPGN in the allograft in renal transplantation, with terminal renal failure as an outcome.

Adolescent↗
PubMed1994

Natural serum TNF antagonists in end-stage renal failure and following renal transplantation.

TNF is clearly involved in allograft rejection but measurement of serum cytokine levels do not reflect reliably the rejection crisis. TNF induces release of soluble receptor parts that are more stable, are catabolized by kidneys and have inhibitory activity. Thus it is crucial to analyse their kinetics during renal function recovery after transplantation to forecast their potential clinical use in rejection monitoring or treatment. A sequential study was performed in 61 patients undergoing kidney graft, compared to 60 graft patients with long follow-up and 15 healthy controls. Soluble TNF and Il2 receptors were measured by ELISA and TNF was measured by RIA. The sTNF-Rs were markedly increased in renal failure, much more than another soluble cytokine receptor, the sIl2-R. Levels progressively decreased with the recovery of renal function and became directly correlated to the renal function. Normal levels were only reached after some weeks. No significant changes were observed during graft rejection at that stage of renal function but p75 were higher after antilympocyte antiserum and tubular necrosis. High sTNF-R did not seem to minimize rejection risk or gravity. In long-standing recipients, sTNF-R rose in some patients, particularly with glomerulonephritis, and may help in monitoring chronic rejection activity. sTNF-R but not sIl2-R markedly accumulate in ESRF and mask any changes that could be helpful in the monitoring of early graft events. However, increased levels above renal impairment (sTNF-R/SCr) may be clinically relevant in late rejection or glomerulonephritides.

Adult↗