Segmental necrosis of the ascending colon in haemodialysis patients.
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Biomedical subjects
Publications and source records attributed to C Legendre.
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Thiopurine methyltransferase (TPMT), one of the enzymes involved in azathioprine metabolism, exhibits a wide range of activity in the normal population. We prospectively evaluated the monitoring of erythrocyte TPMT activity (using a radiochemical method) in kidney transplant recipients with regard to the efficacy of azathioprine. Three patterns in TPMT activity variation were observed. In group 1 patients, TPMT activity rose as early as 8 days after transplantation and steadily until month 3. In group 3 patients, TPMT activity remained unchanged. In group 2 patients, TPMT activity rose at month 1 after transplantation. Interestingly, the incidence of acute rejection was significantly (P < 0.01) different among the 3 groups, with the lowest incidence in group 1 and the highest in group 3. We hypothesized that TPMT activity increase was induced by azathioprine in the patients with the lowest incidence of acute rejection. The inducibility of TPMT activity would then appear to be an interesting marker of azathioprine-induced immunosuppression.
Azathioprine-induced myelosuppression is the most important side effect observed in kidney transplantation. We report a case of severe neutropenia after kidney transplantation due to a thiopurine methyltransferase deficiency. This cause of azathioprine-induced myelotoxicity is rare, but its infectious consequences may be severe. Thiopurine methyltransferase deficiency must therefore be suspected when early and severe leukopenia occurs during azathioprine therapy. Erythrocyte thiopurine methyltransferase activity measurement confirms the diagnosis. Azathioprine and 6-mercaptopurine must afterwards be definitively avoided.
Administration of monoclonal antibodies to CD3 triggers acute and massive release of several cytokines, including tumor necrosis factor alpha (TNF-alpha), essentially T cell-derived. This cytokine release is responsible for the spontaneously reversible acute clinical syndrome observed in most OKT3-treated patients. We found that the first OKT3 injection in human renal allograft recipients led to the release in significant amounts of soluble TNF receptors (TNF-sR55 and TNF-sR75) that are considered main natural inhibitors of TNF bioactivity. As for OKT3-induced TNF-alpha, peak TNF-sR levels were observed 1 hr postinjection, and this release was limited to the first monoclonal antibody injection. A distinct regulation of OKT3-mediated release of TNF-sR75 and TNF-sR55 was observed, since (1) in clear contrast with OKT3-mediated TNF-sR75 induction, TNF-sR55 release was completely blocked by a high dose of corticosteroids prior to OKT3 injection and (2) secretion of TNF-sR75 but not TNF-sR55 correlated with immunoreactive TNF-alpha release. In hemodialyzed patients prior to transplantation and OKT3 treatment, a condition characterized by chronic TNF-alpha release, TNF-sR efficiently block TNF bioactivity. In contrast, the system is overwhelmed by the massive acute TNF-alpha release that follows the first OKT3 injection: in such a condition TNF-sR looses its capacity to counteract TNF bioactivity.
The charts for seven renal transplant recipients who developed Pneumocystis carinii pneumonia were reviewed. They included six men and one woman transplanted a mean of 150 days before the diagnosis of this infection. Six presented at least one episode of acute graft rejection. Cytomegalovirus pneumonia was diagnosed in six of the patients. All patients were treated with cotrimoxazole. Global mortality was 43%. In additional to the classic hypothesis of latent Pneumocystis carinii reactivation in immunocompromised hosts, this and previous reports of outbreaks strongly suggest either a person-to-person transmission or acquisition from the environment. Molecular typing of isolates could be of value in identifying the source of such outbreaks. Chemoprophylaxis should be more systematically administered to renal transplant patients, co-trimoxazole being the drug of choice.
BACKGROUND/AIMS: Hepatitis C virus (HCV) infection by the genotype 1b is significantly associated with a lower rate of response to interferon alfa and with severe liver disease (cirrhosis and hepatocellular carcinoma). This may reflect different intrinsic properties of this genotype 1b and/or chronological differences in the epidemiology of HCV genotypes. To address the issue of variations in genotypes prevalence, we studied in the present report the HCV genotypes of 60 hemodialyzed and kidney recipients according to the date of hemodialysis. METHODS: Anti-HCV antibodies were tested by a second-generation assay (enzyme-linked immunosorbent assay 2 and recombinant immunoblot assay 2). HCV RNA was detected by reverse-transcription polymerase chain reaction. Genotyping was performed by hybridization of type-specific probes to the amplified product from the 5' untranslated region. RESULTS: Genotype 1b accounted for more than two thirds of HCV infection in patients who underwent dialysis before 1977 but less than one third in those hemodialyzed after 1985. In contrast, other genotypes (3a, 4a, 5a) appeared in the 1980s. CONCLUSIONS: These data, obtained in an homogenous group of patients, show a changing pattern of HCV genotype prevalence over time and should be considered when discussing the potential clinical implications of HCV genetic variability.
We report our local experience of two patients with type 1 primary hyperoxaluria (PH1) who received successful isolated cadaver kidney transplantation. The indication of isolated renal transplantation exists for PH1, but it must probably be restricted to the less severe forms of this disease. Recipient and donor selection is crucial.
This paper outlines the different options of transplant procedures in patients with primary hyperoxaluria type 1. Isolated kidney, isolated liver and combined liver-kidney grafting are discussed. Combined liver-kidney grafting appears to be the preferred treatment for patients already in end-stage renal failure. The potential value of the two other procedures is outlined. Guidelines for perioperative care are given. These involve fluid regime, pyridoxine supplementation, immunosuppression and administration of crystallization inhibitors such as phosphate and citrate. Special emphasis is put on selection of appropriate dialysis procedures and reasons why haemodialysis and continuous haemodiafiltration are the methods of choice.
OBJECTIVE: To learn the value of bronchoscopy and biopsy in the early diagnosis of inhalation injury ARDS. SETTING: Burn Center, CHU Saint-Antoine, Paris, France. DESIGN: 130 consecutively admitted burn patients were bronchoscoped on admission. MEASUREMENTS: The appearance of the bronchial tree was recorded, and biopsies were taken from spurs of the proximal and distal branches of the right bronchi. RESULTS: Either bronchoscopy or biopsy was positive in 46 cases. Twenty three of 44 patients with chemical inhalation injury developed ARDS (52%). Of 83 negative cases only 6 developed ARDS (7%). CONCLUSION: Bronchoscopy with biopsy is useful in predicting the development of ARDS in burn patients.
alpha-Glutathione S-transferase (alpha-GST; EC 2.5.1.18) has been advocated as a better marker of hepatocellular damage than the transaminases in toxic and autoimmune hepatitis. We have assessed the potential interest of plasma alpha-GST determination in 94 anti-hepatitis C virus-positive patients with histologically proven chronic hepatitis C (34 women, 60 men, ages 40.0 +/- 11.9 years). Blood samples were assayed for aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase, alkaline phosphatase, and alpha-GST on the same day a liver biopsy was performed. alpha-GST concentrations were significantly above reference values in 64% of patients (compared with 58% for AST, 68% for ALT), and this increase was seen in 52% of patients with normal values for transaminases and a Knodell score > 3. Furthermore, there was a significant correlation between alpha-GST and lobular necrosis score (r = 0.31; P < 0.01). Our findings suggest that association of plasma alpha-GST with ALT may improve the biochemical assessment of liver damage in patients with chronic hepatitis C.
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OBJECTIVES: The relations between the severity of histopathological lesions and epidemiological, clinical and biological data were studied in 86 patients with chronic viral hepatitis C. PATIENTS AND METHODS: None of the patients had any clinical signs of decompensated liver disease. Three groups of patients were individualized according to histopathological findings: 17 (20%) had chronic persistent hepatitis, 48 (56%) had chronic active hepatitis without cirrhosis, and 21 (24%) had cirrhosis. RESULTS: Patients with cirrhosis differed significantly from patients in the two other groups for all biological parameters. With multivariate analysis, alkaline phosphatase activity and serum hyaluronic acid were two independent parameters significantly associated with cirrhosis. A serum hyaluronic acid level above 150 micrograms/L or alkaline phosphatase activity above normal were predictive of cirrhosis with a sensitivity of 87% and a specificity of 93%. None of the parameters in this study provided a clear distinction between patients with chronic persistent and chronic active hepatitis. CONCLUSION: Determination of serum hyaluronic acid and alkaline phosphatase activity as a non invasive index of cirrhosis could be useful for diagnosis and follow-up in patients with chronic viral hepatitis C.
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In a cohort of 483 blood donors positive for antibody to hepatitis C virus on second-generation enzyme-linked immunosorbent, the confirmatory second-generation recombinant immunoblot assay (Ortho Diagnostic Systems) was positive in 172 cases (36%), indeterminate in 113 (23%), and negative in 198 (41%). We further studied 94 of the donors (recombinant immunoblot assay positive in 85, indeterminate in 6, and negative in 3). Alanine transaminase (ALT) activity, assayed on three occasions, was elevated in at least one assay in 85% of the 85 recombinant immunoblot assay-positive donors. Liver disease was present in 95% of these patients (chronic persistent hepatitis, 35%; chronic active hepatitis, 53%; cirrhosis, 7%). Ten of the 13 recombinant immunoblot assay-positive donors with normal ALT activity had liver disease; polymerase chain reaction testing for viral RNA was predictive of liver disease in most cases. Donors with cirrhosis differed significantly from cirrhosis-free donors in terms of age, sex ratio, ALT activity, and excessive alcohol consumption. Three of the 6 recombinant immunoblot assay-indeterminate donors (isolated C 22) who underwent histological examination had elevated ALT activity and liver disease. The 3 recombinant immunoblot assay-negative donors evaluated were free of liver disease. This study shows that anti-HCV second-generation enzyme-linked immunosorbent positivity is confirmed in fewer than 40% of blood donors by the second-generation recombinant immunoblot assay, and that liver disease is present in 95% of recombinant immunoblot assay-positive donors. Recombinant immunoblot assay positivity combined with viremia is frequently associated with the existence of liver disease, regardless of transaminase activity. Excessive alcohol consumption may be an important factor in the onset of cirrhosis in anti-HCV-positive blood donors.
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