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Biomedical subjects

D Samuel

Publications and source records attributed to D Samuel.

At least 145 records · Page 8Linked to original sources

Pretransplantation interferon treatment and recurrence of hepatitis B virus infection after liver transplantation for hepatitis B-related end-stage liver disease.

Orthotopic liver transplantation in patients with hepatitis B-related cirrhosis is commonly complicated by reinfection with the hepatitis B virus, with rapidly progressive liver disease and poor survival rate. We assessed the efficacy of prior therapy with recombinant interferon-alpha on the prevention of posttransplantation hepatitis B virus reinfection. Twenty-two patients with hepatitis B-related cirrhosis waiting for liver transplantation received 3 MU (decreased to 1.5 MU in cases of intolerance) of recombinant interferon-alpha until transplantation. The rates of posttransplantation hepatitis B virus reinfection and survival in this group were compared with those in a group of 26 patients previously given transplants for the same disease but not given interferon therapy. The same protocol of HBs antibody passive immunoprophylaxis was applied after transplantation in both groups. Recombinant interferon-alpha was administered for 14 +/- 7 wk. The treatment had an antiviral effect, with disappearance of serum hepatitis B virus DNA in seven of the eight patients initially positive for hepatitis B virus DNA and disappearance of HBeAg in two of the three patients initially positive for HBeAg. Serum hepatitis B virus DNA remained detectable with polymerase chain reaction at transplantation in 56% of the interferon-treated patients. After transplantation, hepatitis B virus reinfection was more frequent in polymerase chain reaction-positive than in polymerase chain reaction-negative patients (78% vs. 17%, p < 0.05). One patient's condition deteriorated during interferon treatment; this patient was not given a transplant. Two patients (in whom hepatitis B virus DNA disappeared from serum) improved so markedly during treatment that they were not given transplants.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Liver transplantation in European patients with the hepatitis B surface antigen.

BACKGROUND: The role of liver transplantation in patients positive for the hepatitis B surface antigen (HBsAg) is controversial because of the high rate of recurrent hepatitis B virus (HBV) infection. It has not been determined whether this risk is greater for certain patients and whether the administration of anti-hepatitis B surface antigen (anti-HBs) immune globulin is beneficial. METHODS: We conducted a retrospective study at 17 European centers of 372 consecutive HBsAg-positive patients who underwent liver transplantation between 1977 and 1990. Recurrence of HBV infection was defined as the reappearance of HBsAg in serum. RESULTS: For all 334 patients with follow-up data, the mean (+/- SE) three-year actuarial risk of recurrence of HBV was 50 +/- 3 percent. The risk was 67 +/- 4 percent among 163 patients with HBV-related cirrhosis, 32 +/- 5 percent among 110 patients with cirrhosis related to hepatitis delta virus, 40 +/- 16 percent among 14 patients with fulminant hepatitis delta infection, and 17 +/- 7 percent among 39 patients with fulminant HBV infection (P < 0.001). Among the patients with HBV-related cirrhosis, the risk of HBV recurrence was greatest (83 +/- 6 percent) in those who were seropositive for HBV DNA at the transplantation and lowest (58 +/- 7 percent) in those with neither HBV DNA nor hepatitis B e antigen detectable in serum. With respect to the use of passive prophylaxis with anti-HBs immune globulin, the risk of HBV recurrence was 75 +/- 6 percent among the 67 patients given no immunoprophylaxis, 74 +/- 5 percent among the 83 treated for two months, and 36 +/- 4 percent among the 209 treated for six months or longer (P < 0.001). In a multivariate analysis the predictors of a lower risk of HBV recurrence were the long-term administration of the immune globulin, hepatitis delta virus superinfection, and acute liver disease. For the entire study cohort, survival was 75 percent at one year and 63 percent at three years, but for those in whom HBV infection recurred, survival was 68 percent at one year and 44 percent at three years. CONCLUSIONS: In this retrospective study of HBsAg-positive patients, liver transplantation had better results in those who had fulminant hepatitis or delta virus superinfection. An absence of viral replication at the time of transplantation and long-term immunoprophylaxis were associated with a reduced risk of recurrent HBV infection and reduced mortality.

Actuarial Analysis↗

A comparison of the binding of biotin and biotinylated macromolecular ligands to an anti-biotin monoclonal antibody and to streptavidin.

A competitive enzyme immunoassay was used to study the binding of biotinylated macromolecular ligands and d-biotin to an anti-biotin monoclonal antibody and to streptavidin. Solid phase BSA-c-biotin competed with biotin or biotinylated macromolecular ligands in solution for receptor binding. The concentration of d-biotin required to inhibit streptavidin binding to solid phase BSA-c-biotin by 50% was 11.5 pM. This streptavidin-biotin interaction was taken as having an affinity/avidity index of 100 and all other receptor-ligand interactions were calculated relative to this. The avidity indices calculated for streptavidin interactions with BSA-c-biotin and IgG-biotin were 17.6 and 6.6 respectively, whereas for anti-biotin the values for these ligands were 20.5 and 19.9 respectively. The interaction of anti-biotin with d-biotin had an affinity index of 0.001. Although streptavidin has the greatest binding affinity for d-biotin, its avidity for biotinylated ligands was considerably lower and comparable to that observed for anti-biotin-biotinylated macromolecule interactions.

Animals↗

Patterns and mechanisms of hepatitis B/hepatitis D reinfection after liver transplantation.

Viral recurrence is the limiting factor in orthotopic liver transplantation (OLT) for hepatitis B virus (HBV) related liver disease. In fact, high rates of HBV infection of the transplanted liver are reported, followed by the recurrence of liver disease in a high percentage of cases. The importance of reinfection stimulates the study of its modalities and mechanisms in order to better identify preventive measures and better select patients for OLT. In HBV and HDV positive patients, the outcome of liver transplantation appears significantly better than in patients that are solely HBV positive, in spite of a high rate of HDV reinfection. Long-term analysis (5 years) of HBV and HDV infection, using the PCR technique, in 15 patients transplanted for an HBV/HDV positive liver disease and treated with anti-HBs immunoglobulin (HBIG), revealed that all patients experienced an HDV reinfection, but only about 7 were still harboring the virus after four years of follow-up. HDV reinfection was either associated to HBV reinfection or isolated whereas no cases of HBV isolated reinfection was observed. Isolated HDV reinfection was frequent and transient in all but one case that was superinfected by HBV. Infected peripheral blood mononuclear cells seem to be implicated in HBV superinfection of HDV infected liver. Liver damage was observed only in cases of HBV/HDV co-infection, suggesting that, in vivo, HBV is necessary to produce liver damage although it is not essential for HDV absorption to target cells, HDV penetration of these cells or HDV genomic replication. In addition, in isolated HDV infection, transient HDV viraemia and its low levels suggest that, perhaps in these patients HDV uses a very limited presence of HBV or alternative ways which are not efficient enough for envelope production. These data suggest that, particularly in HDV positive patients, antiHBs Ig administration, which has previously been proven to significantly reduce HBV reinfection in HBsAg-positive patients, may be useful in changing the natural history of repetition of the original viral infection and liver disease after OLT.

Follow-Up Studies↗

Hepatitis C virus RNA and hepatitis B virus DNA in serum and liver of patients with fulminant hepatitis.

BACKGROUND: The role of hepatitis C virus (HCV) in the development of fulminant hepatitis is poorly understood. METHODS: The polymerase chain reaction was used to detect HCV RNA and hepatitis B virus (HBV) DNA in serum and liver of 40 patients with fulminant or subfulminant hepatitis. RESULTS: HCV RNA was detected in none of the 23 subjects with hepatitis B surface antigen (HBsAg)-negative hepatitis of unknown etiology. HBV DNA was found in 1 of these 23 subjects. In contrast, 8 of the 17 patients with HBsAg-positive hepatitis were HCV RNA positive. Among the latter, 5 had immunoglobulin (Ig) M antibody to hepatitis B core antigen (anti-HBc) and thus were acutely coinfected by HBV and HCV, whereas 3 others without IgM anti-HBc had superinfection by HCV. The active replication of HCV in the liver was shown by detection of high titers of HCV RNA and of negative-stranded HCV RNA. CONCLUSION: This investigation therefore shows no evidence of a role for HCV infection in sporadic cases of fulminant hepatitis without defined etiology. However, it suggests that HCV might be implicated in a significant number of patients with HBV-related fulminant hepatitis.

Adolescent↗

Pregnancy in liver transplant recipients: course and outcome in 19 cases.

OBJECTIVE: Our aim was to evaluate the course and outcome of pregnancy in orthotopic liver transplant recipients. STUDY DESIGN: We report the course and outcome of 19 pregnancies in 19 orthotopic recipients since 1985, out of 775 patients who have undergone liver transplant in our center. Statistical analysis was based on the chi 2 test with a 95% confidence interval, when appropriate. RESULTS: There were four spontaneous abortions and three therapeutic abortions for impaired liver function. One current pregnancy is uncomplicated at 19 weeks' gestation. Eleven women have given birth to 11 healthy infants at 38 +/- 1.5 weeks' gestation. There were no preterm deliveries. Birth weight was normal for gestational age in 10 of the 11 cases, with a mean value of 2990 +/- 370 gm. The main complications in the 11 successful pregnancies were hypertension in three and graft dysfunction at 37 weeks' gestation in another. CONCLUSION: Pregnancy is successful in a large proportion of liver transplant recipients, but it must be planned and managed as a high-risk situation by both an obstetrician and a surgeon.

Abortion, Spontaneous↗

Low prevalence of precore mutations in hepatitis B virus DNA in fulminant hepatitis type B in France.

The presence of mutants of the precore region of the hepatitis B virus genome was investigated in French patients with fulminant hepatitis. Only one of the 10 subjects had a detectable mutation by direct sequencing. On the other hand, 2/10 and 3/10 had evidence of coinfection by hepatitis D virus and hepatitis C virus. These results indicate that the precore stop mutation at codon 28 is not a general condition in fulminant hepatitis B and might reflect epidemiological factors.

Adult↗

Liver transplantation in cirrhosis due to hepatitis D virus infection.

In a series of 49 patients transplanted for cirrhosis due to hepatitis D virus (HDV) infection and receiving anti-HBs immunoglobulins, the 2-year actuarial rate of hepatitis B virus (HBV) reinfection was only 13%, a prevalence much lower than the 29% rate in patients transplanted for HBV-DNA-negative cirrhosis and the 96% rate in patients transplanted for HBV-DNA-positive cirrhosis. HBV reinfection after transplantation in patients with cirrhosis due to HDV infection was invariably associated with HDV reinfection. In a few patients, in the absence of HBV reinfection, transient replication of HDV took place and was not associated with liver lesions of hepatitis. In conclusion, patients with cirrhosis due to HDV infection are good candidates for liver transplantation.

Hepatitis B Surface Antigens↗

Effects of lesion of the cholinergic basal forebrain nuclei on the activity of glutamatergic and GABAergic systems in the rat frontal cortex and hippocampus.

The effects of cholinergic basal forebrain lesions on the activity of the glutamatergic and GABAergic systems were investigated in the rat frontal cortex and hippocampus. Bilateral quisqualic acid injections in the nucleus basalis magnocellularis (NBM) at the origin of the main cholinergic innervation to the neocortex induced a cholinergic deficit in the cerebral cortex 15 days later, as shown by the marked selective decrease in cortical choline acetyltransferase (CAT) activity observed. Concurrent alterations in the kinetic parameters of high affinity glutamate uptake consisting mainly of a decrease in the Vmax were observed in the cerebral cortex. These changes presumably reflect a decreased glutamatergic transmission and provide support for the hypothesis that cortical glutamatergic neurons may undergo the influence of cholinergic projections from the NBM. Surprisingly, similar alterations in the glutamate uptake process were found to occur at hippocampal level in the absence of any significant change in the hippocampal cholinergic activity. These data indicate that the NBM may contribute to regulating hippocampal glutamatergic function without interfering with the hippocampal cholinergic innervation that mainly originates in the medial septal area-diagonal band (MSA-DB) complex. No change in parameters of GABAergic activity, namely the glutamic acid decarboxylase (GAD) activity and high affinity GABA uptake, were observed in any of the structures examined. In a second series of experiments involving bilateral intraventricular injections of AF64A, marked survival time-dependent decreases in CAT and high affinity choline uptake activities but no significant change in the high affinity glutamate uptake rate were observed in the hippocampus. No significant change in either parameters of cholinergic activity or in the glutamate uptake was concurrently observed in the cerebral cortex. The GABAergic activity was again unaffected whatever the survival time and the structure considered. Taken as a whole, these data suggest that basal forebrain projections originating in the NBM may play a major role in regulating glutamatergic but not GABAergic function in both the cerebral cortex and the hippocampus; whereas the glutamatergic and GABAergic activities in these two structures may not be primarily under the influence of the cholinergic projections from the MSA-DB complex.

Animals↗

Fipexide-induced fulminant hepatitis. Report of three cases with emergency liver transplantation.

Fipexide belongs to a new class of cognition activators and is noted for its lack of amphetamin-like side effects. We describe three patients who developed fulminant hepatic failure less than 2 months after beginning fipexide administration. The mean interval from the onset of jaundice to the onset of encephalopathy was 8 days. Emergency liver transplantation was undertaken when factor V was 20% of normal or less and coma developed. All patients were transplanted less than 1 week after the onset of encephalopathy. Two survived and one died immediately after transplantation. Histologic examination of the livers revealed massive liver cell necrosis, predominantly centrilobular, and a moderate inflammatory infiltrate within the portal spaces. We conclude that fipexide can induce massive liver cell necrosis and fulminant liver failure. As a result of this life-threatening complication, reconsideration of the indications for this drug is warranted.

Adolescent↗

Intracerebroventricular administration of neuropeptide Y affects parameters of dopamine, glutamate and GABA activities in the rat striatum.

The effects of intracerebroventricular (ICV) injection of neuropeptide Y (NPY) on parameters of dopamine (DA), glutamate (Glu) and gamma-aminobutyric acid (GABA) activities were investigated in the rat striatum. NPY (1.17-4.70 nmol) induced a dose-dependent increase in the striatal endogenous DA release monitored in freely moving animals by means of a voltammetric method. Maximal increase was observed about one hour after the peptide injection. This result is consistent with the hypothesis that NPY may influence striatal DA turnover in a facilitatory manner by activating DA release. DA, DOPAC, Glu and GABA endogenous contents as well as 3H-Glu and 3H-GABA synaptosomal high affinity uptakes were examined one hour after NPY ICV administration at the same dose range in chloral hydrate-anesthetized animals. Depending on the NPY dose injected, opposite changes in Glu uptake were observed, suggesting that NPY has a bimodal influence on glutamatergic transmission. The Glu uptake rate increased markedly at 1.17 nmol NPY and decreased at 4.70 nmol, which may reflect an activation and an inhibition of the striatal Glu transmission, respectively. In parallel, the GABA uptake was found to decrease slightly at the higher doses of NPY tested, whereas no significant alteration of the striatal concentrations of either DA, DOPAC, Glu or GABA was observed. These results indicate that NPY may be involved in regulating the activity of nigral dopaminergic and cortical glutamatergic afferent pathways and that of intrinsic GABA neurons in the rat striatum.

3,4-Dihydroxyphenylacetic Acid↗

[Relapse prevention in liver transplant patients treated for liver involvement due to hepatitis B virus].

Controversy surrounds the indication of liver transplantation in patients with hepatitis B virus infection. The major problem is the very high risk of infection of the graft. Some investigators have suggested that the presence of HBsAg is a contraindication to liver transplantation. Between February 1975 and December 1990, 178 HBs positive patients were transplanted at Paul Brousse Hospital in Professor H. Bismuth's Department, 137 for post hepatitis cirrhosis and 41 for fulminant hepatitis. Since April 1984 we have decided long term immunoprophylactic therapy for all patients with HBs infection. But only from August 1987 our supply of purified anti HBs immunoglobulin has been adequate to treat all our patients according to the following protocol: 10.000 IU during the peroperative phase, 10.000 IU immediately after intervention, 10.000 IU every day for the first 6 days, 10.000 IU when the anti HBs levels were under 150 IU/l. One hundred thirty-nine patients were treated by this method. 110 cleared HBs antigen from their sera and their liver were biologically and histologically free of B virus infection. 29 patients showed reappearance of HBs antigen in their sera and nearly all of them developed objective, histologically confirmed, graft lesions. These lesions are those of classical infection: acute hepatitis, active chronic hepatitis and cirrhosis. So 79% of patients were successfully treated with a follow up of 45 months to 6 months. We also studied the prognostic factors under treatment. The study shows: in the case of fulminant hepatitis, 93% success versus 77% in post hepatitis cirrhosis; in the case of Delta superinfection, 94% success versus 66% with pure B infection; in the absence of HBVDNA in the patient's sera before transplantation, 92% success versus 20% in the presence of HBVDNA. For a better understanding of the overall results, the two following parameters have to be considered: some patients relapsed after stopping their treatment, some other patients, despite repositivation of HBs antigen in their sera showed a paradoxal good evolution. These considerations enable us to obtain HBVDNA positive patients: 10% success, HBVDNA negative patients: Fulminant hepatitis: 100% success B Delta post hepatitis cirrhosis: 100% success B post hepatitis cirrhosis: 92% success.

Hepatitis B↗

Effects of riluzole (2-amino-6-trifluoromethoxy benzothiazole) on striatal neurochemical markers in the rat, with special reference to the dopamine, choline, GABA and glutamate synaptosomal high affinity uptake systems.

Riluzole, a new compound with anticonvulsant properties, was found to induce a dose-dependent decrease in the uptake of 3H-dopamine, 3H-GABA and 3H-glutamate into striatal synaptosomes when added to the incubation medium or after in vivo administration, whereas an inhibition of 3H-choline uptake was detected only in the in vitro experiments. Interestingly, riluzole affected 3H-dopamine and 3H-glutamate uptake differentially since 3H-dopamine uptake was found to be more sensitive to the compound. Moreover, riluzole inhibited 3H-dopamine uptake competitively and 3H-glutamate uptake non-competitively, which further suggests that the action of the compound is selective. After in vivo injection, riluzole did not affect the striatal dopamine, DOPAC, serotonin, 5HIAA, glutamate, aspartate or GABA contents. Since this compound was previously reported to induce a decrease in the spontaneous release of glutamate, serotonin, dopamine and possibly acetylcholine, the hypothesis is put forward that riluzole may, at least at high concentrations, have general effects on the striatal nerve terminals affecting both the uptake and release processes. This action may be correlated with the recently identified blocking properties of the compound on the sodium channels, as previously shown for local anaesthetics.

3,4-Dihydroxyphenylacetic Acid↗