Study of the toxicity of various concentrations of 2-3-butanediol in the isolated perfused rat liver.
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Animals↗
Biomedical subjects
C Legendre
Publications and source records attributed to C Legendre.
Creatine kinase-BB: a marker of liver sinusoidal damage in ischemia-reperfusion.
Cell damage within the sinusoidal lining of human liver grafts during transplantation is an early event that is critical in ischemia-reperfusion injury and probably plays a key role in primary liver dysfunction after transplantation. No simple biochemical marker for sinusoidal injury is currently available. Because creatine kinase activity has been described in heart endothelial cells, we hypothesized that release of this enzyme might serve as an index of sinusoidal injury. To test this hypothesis, we used several in vivo and in vitro experimental models. Occlusion of the rat hepatic pedicle in situ for 60 min (normothermic ischemia) induced a significant increase in serum creatine kinase levels relative to those in laparotomized controls (2,530 +/- 530 vs. 389 +/- 64 IU/L, mean +/- SEM; p < 0.005). In the isolated perfused rat liver, 60-min ischemia induced early (< or = 3 min) creatine kinase and AST release (0.87 +/- 0.14 vs. 0.08 +/- 0.01 IU/min/gm liver, respectively). A similar phenomenon was observed after 24-hr or 48-hr hypothermic conservation in University of Wisconsin solution. Electrophoretic analysis and immunoinhibition studies showed that creatine kinase activity comprised creatine kinase-BB (approximately 50%) and mitochondrial creatine kinase. Trypan blue infusion showed a loss of viability in sinusoidal cells, whereas hepatocytes were relatively spared. Finally, murine sinusoidal cells were isolated, cultured and then lysed by a freeze-thaw cycle and sonication. Creatine kinase activity was found in endothelial cells (creatine kinase-BB), Kupffer cells (creatine kinase-BB) and Ito cells (creatine kinase-MM). Creatine kinase-BB was not found in hepatocytes, but mitochondrial creatine kinase was detected.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[T CD57+ lymphocytes in kidney transplanted patients. Phenotypic and functional study].
Phenotypic analysis showed a significant increase of CD3+/CD57+ lymphocyte subpopulation in 88 kidney-transplanted patients when compared with non-transplanted patients. No clear correlation was found between the increase of this cell subpopulation and renal function, immunosuppressive regimen, and allogenic or viral stimuli, when each of these factors was considered. Conversely, there was a significant correlation between the proportion of CD3+/CD4+/CD57+ cells and the post-transplant follow-up period. Finally, functional study of CD3+/CD57+ cells suggested that they have suppressive properties, in vitro.
Antigens, CD↗
[Effect of pregnancy on renal function after transplantation].
Between 1968 and 1991, 36 pregnancies were reported in 28 patients who had undergone kidney transplantation at the Necker hospital, Paris. Pregnancies with favourable graft outcome were compared with those accompanied by significant deterioration of graft function and requiring haemolysis. The risk factors for renal function deterioration during pregnancy in kidney-transplanted women were found to be an initial nephropathy induced or aggravated by a previous pregnancy, an alteration, even mild, of graft function, hypertension, even controlled by treatment, an HLA mismatch and several episodes of acute graft rejection soon after kidney transplantation.
Female↗
[Acute renal failure. Etiology, physiopathology, diagnosis, principles of the treatment].
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Acute Kidney Injury↗
Intrasplenic hepatocellular transplantation corrects hepatic encephalopathy in portacaval-shunted rats.
The aim of this work was to evaluate the effect of intrasplenic hepatocellular transplantation on hepatic encephalopathy in an experimental model of chronic liver failure induced by end-to-side portacaval shunt in the rat. Inbred male Wistar Furth rats were divided into three groups: rats subjected to portacaval shunt (n = 10), rats subjected to portacaval shunt and intrasplenic hepatocellular transplantation of 10(7) hepatocytes isolated from livers of syngeneic rats (n = 10) and sham-operated rats (n = 10). Behavior tests were performed in a blind fashion at 3 wk, at 2 mo and at 3 mo after surgery. Spontaneous activity and nose-poke exploration by individual rats were studied in automated open field boxes equipped with infrared cells. Each cell beam interruption was automatically recorded on a microcomputer and transformed into a score index (counts/hour). Plasma levels of amino acids, ammonia and total biliary acids were measured. Portacaval shunt rats showed reduced spontaneous activity and nose-poke exploration scores. Intrasplenic hepatocellular transplantation significantly increased spontaneous activity after 2 mo and improved nose-poke exploration after 3 wk. At 3 mo, spontaneous activity and nose-poke exploration in portacaval shunt/intrasplenic hepatocellular transplantation rats were not significantly different from those of sham rats. Increases in plasma ammonia levels after portacaval shunt were not corrected. Amino acid imbalance and bile acid concentration in plasma were partially corrected by intrasplenic hepatocellular transplantation. These data show that intrasplenic hepatocellular transplantation can correct the neurological symptoms of hepatic encephalopathy in an experimental model of chronic liver failure and suggest that intrasplenic hepatocellular transplantation might be of therapeutic interest in chronic liver failure.
Animals↗
Hepatitis C virus in kidney recipients. Epidemiology and impact on renal transplantation.
In an attempt to evaluate the prevalence, kinetics and impact of HCV infection in renal transplantation, we analyzed 140 kidney recipients according to the histopathological status of the liver. Thirty-three HBsAg-negative patients had chronic active hepatitis, 73 HBsAg-negative patients had a normal liver, 21 HBsAg-negative kidney recipients had minimal pathological changes and 13 patients had HBsAg-positive cirrhosis. Serum antibodies to HCV were detected using the ELISA from Ortho Diagnostic and confirmatory tests using the Ortho recombinant-based immunoblot assays. The overall prevalence of antiHCV antibodies was 23.6%. AntiHCV were more frequently present in HBsAg-negative patients with chronic active hepatitis (60.6%) than in HBsAg-negative patients with normal livers (8.2%) (p less than 0.0001) or minimal liver changes (33.3%) (NS) or in HBsAg-positive patients with cirrhosis (0%) (p less than 0.001). The recombinant-based immunoblot assays confirmed antiHCV-positive ELISA results in 86.7% of patients. Among the 27 antiHCV-positive kidney recipients who had serial serological follow-up, 10 (37.0%) were already positive at transplantation and remained antiHCV-positive during follow-up. Eleven patients (40.8%) acquired antiHCV an average of 95 months after renal transplantation, while antiHCV disappeared an average of 111 months after transplantation in six (22.2%), who had antiHCV prior to transplantation. The kinetics of antiHCV antibodies did not differ according to liver histology. Patient and graft survival were not different in antiHCV-positive and antiHCV-negative kidney recipients irrespective of liver histology, and there was no difference in survival between antiHCV-positive and antiHCV-negative patients with chronic hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Pancreas and islet transplantation in man.
The results of pancreas transplantation have greatly improved, the overall patient and graft 1-year survival rates now being 89 and 62%, respectively. A technically successful graft ensures a near-normal glucose metabolism in most cases, and improves the patient's quality of life. However, pancreas transplantation is not a life-saving procedure and because of the necessary permanent immunosuppression it is usually performed in patients in whom a kidney transplant is needed or has been previously established. In such patients the other diabetic chronic complications are often advanced and limit the potential benefit of pancreas transplantation, but it seems premature to extend the indications to early stage diabetes. Islet transplantation has many potential advantages, mainly the possibilities of immune alteration and immune protection of the transplant that could allow transplantation to be performed without immunosuppression and the use of xenogenic tissue. Major limiting factors are the high numbers of islets necessary to ensure insulin independence and the low yield of islet isolation from adult pancreas. Encouraging, albeit preliminary results have been recently reported in man.
Diabetes Complications↗
Prediction of successful allograft rejection retreatment with OKT3.
OKT3 is considered to be effective in the prophylaxis and treatment of rejection. However, anti-OKT3 immunization is still a major side-effect. Only the IgG antiidiotypic component of the response is responsible for neutralization of OKT3 therapeutic activity by inhibiting OKT3's binding to T cells (i.e., blocking antibodies). It has recently been reported that successful OKT3 retreatment could be performed in patients showing circulating anti-OKT3 antibodies assessed by ELISA, which does not distinguish between blocking and nonblocking antibodies. The aim of this study was to investigate the role of these two types of anti-OKT3 antibodies for their capacity to interfere with effective OKT3 retreatment. Twelve cadaver renal allograft recipients who received OKT3 inducing therapy, were given a second 10 day-course of OKT3 for treatment of rejection. Circulating CD3+ cells were sequentially monitored. Anti-OKT3 antibodies were detected by using both conventional ELISA and an immunofluorescence inhibition test specifically detecting blocking antibodies. OKT3 and the patient's serum were incubated for 30 min at 4 degrees C, and 2 x 10(5) normal T cells were added (30 min at 4 degrees C). After washing, the cells were incubated with FITC goat antimouse antiserum. Fluorescent cells were counted using a FACS analyzer. In 10 patients, at the end of the 10-day second course, less than 10% circulating CD3+ cells were detected. None of these patients had detectable antibodies in the IF inhibition assay at the beginning of retreatment, irrespective of anti-OKT3 antibody titers detected by ELISA. In contrast, in two patients, OKT3 therapy was ineffective: more than 50% circulating CD3+ cells were detected and OKT3 treatment had to be interrupted soon after it was initiated. In both of them, blocking antibodies were detected by the IF-inhibition assay. These results suggest that specific detection of blocking antiidiotypic antibodies by the IF inhibition assay is a reliable parameter for predicting the feasibility of OKT3 retreatment, avoiding misuse of this expensive therapy.
Adolescent↗
Absence of hepatitis delta virus infection in chronic hemodialysis and kidney transplant patients in france.
Hemodialyzed patients and kidney recipients are frequently multiply-transfused and infected by hepatitis B virus (HBV). Hepatitis delta virus (HDV) has a symbiotic association with HBV. The prevalence of HDV infection has, surprisingly, not been assessed in patients in hemodialysis or renal transplantation setting. We retrospectively studied the prevalence of serum delta antigen and antidelta antibodies by a microenzyme-linked immunosorbent assay in 77 of the 80 HBsAg-positive patients who underwent a kidney transplantation over a 10-year period. Of these patients, 73% had active HBV replication as assessed by the presence of serum HBV DNA and 65% had a biopsy-proved chronic active hepatitis, including cirrhosis. None of our patients had any marker of HDV infection at the end of the hemodialysis period or at the end of follow-up in transplantation. These results establish that HDV superinfection has indeed been extremely rare during end-stage renal failure and kidney transplantation in France, in contrast to HBV reactivation or hepatitis C virus infection.
DNA, Viral↗
Gd-DOTA-enhanced MR imaging and color Doppler US of renal allograft necrosis.
In 21 recipients of renal transplants suspected of allograft necrosis, the authors correlated the results of imaging to pathologic and histologic data in order to describe the magnetic resonance (MR) imaging and color Doppler ultrasonographic (US) characteristics of infarction. All patients underwent MR imaging performed with and without gadolinium tetraazacyclododecanetetraacetic acid (DOTA) and color Doppler US. Nonenhanced T1-weighted images showed no obvious changes, whereas nonenhanced T2-weighted images demonstrated a slight increase in signal intensity in areas of ischemic necrosis and low or heterogeneous signal intensity in areas of hemorrhagic necrosis. Gd-DOTA-enhanced MR images showed no contrast material uptake in infarcted areas. Color Doppler US characteristics of infarction included absence of Doppler signal and alteration of the cortical echogenic structure, particularly in cases of ischemic necrosis. Color Doppler US allows measurement of vascular resistance and assessment of intrarenal vasculature and the renal pedicle. Gd-DOTA-enhanced MR imaging is useful in confirming the diagnosis of infarction and provides an accurate evaluation of the extent of the infarct.
Adult↗
Toxoplasma colitis in the acquired immunodeficiency syndrome.
In patients with acquired immunodeficiency syndrome (AIDS), toxoplasmosis almost exclusively involves the central nervous system (CNS), and extra-CNS organ infection is rare. We report a case of Toxoplasma gondii colitis in a patient with AIDS characterized by the following: 1) onset of diarrhea was simultaneous with disseminated toxoplasmosis; 2) T. gondii was found in colonic biopsies, whereas other infectious causes of diarrhea had been ruled out; 3) diarrhea was cured by anti-Toxoplasma therapy.
Acquired Immunodeficiency Syndrome↗
[Aseptic osteonecrosis of the knee induced by corticoids. MRI aspects].
Authors report the results of a series of 29 knees examined by magnetic resonance imaging in 16 patients subjected to a long-term corticosteroid therapy (6 systemic lupus erythematosus and 10 kidney transplanted people). Abnormal signals of condyles or tibial plateaus were observed in 12 patients (19 knees). Lesions, which were asymptomatic in 37% of the cases studied, mostly showed (12/24 condyles) a fatty signal area marked out by a hypointense signal strip in T1 edged with a hyperintense signal in T2. Some developed lesions were hypointense whichever the sequence. Our study confirmed the frequency of the lateral condyle involvement (60%) and the bilateral aspect of the lesions (50%) in osteonecrosis of the condyles following the corticosteroid therapy. The associated lesions of articular surfaces (3 cases) could be well assessed through magnetic resonance imaging on T2 or T2* weighted images. In two cases, the abnormal signals of the condyles suggesting a medullary edema (hypointense signal in T1 and hyperintense signal in T2) spontaneously disappeared 6 and 9 months after their discovery. Abnormal signals related to medullary infarcts (10 knees) were always associated with abnormal condyles. Most time their aspect in magnetic resonance imaging, except old calcified lesions, was characteristic: serpiginous hypointense signal isolating areas of fatty signal edged with a hyperintense signal strip in T2. In risk patients, magnetic resonance imaging allows early detecting knee necroses, precising the extent of epiphyseal and metaphyso-diaphyseal lesions and their impact on articular surfaces.
Adult↗
[Hepatitis C in kidney recipients. Epidemiology and impact on kidney transplantation].
In an attempt to evaluate the prevalence, the kinetics and the impact of HCV infection in renal transplantation, we analyzed 140 kidney recipients according to hepatic histology: 33 HBsAg negative patients had chronic active hepatitis, 73 HBsAg negative patients had a normal liver, 21 HBsAg negative kidney recipients had minimal pathological changes and 13 patients had HBsAg positive cirrhosis. Serum antibodies to HCV were detected using the ELISA test. The overall prevalence of anti-HCV antibodies was 24.3 percent: anti-HCV were more frequently present in HBsAg negative patients with chronic active hepatitis (57.5 percent) than in HBsAg negative patients with normal liver (8.2 percent) (P less than 0.0001) or minimal changes (33.3 percent, NS) and HBsAg positive patients with cirrhosis (15.4 percent) (P = 0.02). Among the 30 anti-HCV positive kidney recipients with serological follow up, 13 (43.3 percent) had anti-HCV antibodies at the time of transplantation and kept anti-HCV during follow up, 11 (36.7 percent) acquired anti-HCV after renal transplantation in a mean time-lag of 95 months while 6 (20 percent), who had anti-HCV prior to transplantation, exhibited negativation of anti-HCV antibodies in a mean time-lag of 111 months after transplantation. The kinetics of anti-HCV antibodies was the same irrespective of the liver status. Patients and grafts survivals were not different in anti-HCV positive and anti-HCV negative kidney recipients, whatever the hepatic histology. Our data suggest that, in kidney transplantation, a) the prevalence of anti-HCV antibodies is around 24 percent in kidney recipients and varies greatly according to hepatic histology; b) anti-HCV antibodies are not systematically associated with the development of chronic liver disease; c) post-transfusion hepatitis as well as so called community acquired hepatitis may occur in transplantation follow up; d) HCV infection does not clearly influence the survival of allograft or that of kidney recipients.
Adult↗
Effect of bile acids on ischemia-reperfusion liver injury.
We investigated whether stimulation of bile flow by taurocholic acid (TCA), ursodeoxycholic acid (UDCA) or its taurine conjugate (TUDCA) could protect the liver from ischemia-reperfusion injury. The isolated perfused rat liver model was used. In livers perfused without bile acids (n = 8), 60 min of ischemia induced a significant reduction in bile flow and in portal flow, together with a marked increase in LDH, AST and uric acid release in the perfusate. These alterations were maximal at the beginning of reperfusion. In livers perfused with TCA (n = 6), UDCA (n = 7) or TUDCA (n = 6), bile flow was significantly increased as compared to controls during the pre-ischemic phase, as well as during the reperfusion phase. However, no significant improvement was observed in any of the biochemical, hemodynamic or histologic parameters studied. The results show that stimulation of bile flow either by TCA, UDCA or TUDCA does not reduce ischemia-reperfusion liver injury. Furthermore, the results do not provide evidence for a cytoprotective effect of UDCA or TUDCA in this model of liver injury.
Animals↗
Angiotensin-converting enzyme (ACE) inhibitors have been reported to induce or worsen anemia in patients on hemodialysis.
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Adult↗
Morphologic and ultrastructural effects of Maalox TC on human gastric and duodenal mucosa.
Prostaglandins (PGs) and aluminum-containing antacids (Al.AAs) are effective in preventing gastric and duodenal lesions induced by neutralizing agents. The efficacy of Al.AAs is thought to be due to neutralizing properties and to stimulation of endogenous PGs synthesis. Liquid Maalox has the same effect as cimetidine 400 mg on postprandial duodenal acid load. In numerous prospective studies, Al.AAs have been shown to be as effective as cimetidine in the short-term treatment of duodenal ulcer (DU). Maalox TC at a dosage of 3 tablets b.i.d. provides an effective method for preventing DU relapse. Its effect is similar to that of nighttime cimetidine. Meta-analysis of prospective trials suggests that Al.AAs prevent stress ulcers more effectively than does cimetidine. It has been suggested that Al.AA acts by inducing surface epithelial cell disruption. Al-induced mucosal protection could be caused by a stimulated release of endogenous PGs, induced by Al microcrystal penetration of cells. In a recent study, we showed that small amounts of Al were absorbed by human gastric mucosa and accumulated in lysosomes; however, we did not observe any histological or ultrastructural lesions of the gastric mucosa. Prostaglandins (enprostil, misoprostol, and rioprostil) are as effective as cimetidine, but less effective than ranitidine, in healing DU. Enprostil and rioprostil have been shown to be as effective as ranitidine in treating gastric ulcer (GU). Moreover, enprostil inhibits postprandial gastrin release, whereas H2-blockers increase gastrin levels. Coadministration of misoprostol with aspirin is highly effective in healing aspirin-induced gastroduodenal lesions. Moreover, cotreatment with misoprostol was associated with a marked decrease in GU in patients with osteoarthritis receiving NSAIDs chronically.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Corticosteroid inhibition of the OKT3-induced cytokine-related syndrome--dosage and kinetics prerequisites.
The data presented extend to a larger series of 27 consecutive renal allograft recipients treated prophylactically with OKT3 our previous observation that the acute OKT3-induced clinical syndrome is related to massive release in the circulation of some cytokines, among which are tumor necrosis factor and interferon gamma. In addition, a pilot randomized study was set up including 12 consecutive patients receiving high-dose corticosteroid treatment (0.5 g solumedrol) either before or at the same time as the first OKT3 injection. Results confirm that when corticosteroids are given in sufficient amount and, importantly, 1 hr before the first OKT3 injection, they significantly decrease the release of both tumor necrosis factor and interferon gamma. In addition, the pretreatment with corticosteroids may totally abolish the IL-2 release induced by OKT3. Given the key role the massive although transient cytokine release plays in determining the OKT3-induced acute syndrome, these results provide the biological basis supporting a precise kinetics of administration of high-dose corticosteroids to better decrease the severity of the clinical reaction.
Adrenal Cortex Hormones↗