Search PubMed⌕ Search

Biomedical subjects

D Samuel

Publications and source records attributed to D Samuel.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

[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↗
PubMed1992

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↗
PubMed1992

Monokine gene expression in normal human liver: selective involvement of the portal compartment.

Monokines play a major role in the regulation of hepatocyte functions. To document a possible in situ production of these mediators under physiological conditions, expression of IL-1 beta and of IL-6 genes was analyzed by in situ hybridization in four histologically normal human livers. We detected cells containing IL-1 beta mRNA or IL-6 mRNA in all cases. Cells expressing either the IL-1 beta gene or the IL-6 gene were found with equal frequency and were similarly distributed. Although present in all liver compartments, they were selectively enriched in portal areas, in which they were detected both in endothelial positions and in perivascular connective tissues. Few positive cells were observed in hepatic lobules, most of them being located in the walls of centrolobular veins, in an endothelial position. Subcapsular cells were also shown to express monokine genes. The location of positive cells and their pattern of labelling suggested that macrophages, fibroblasts and endothelial cells were the main cell populations expressing monokine genes. In contrast, Kupffer cells, biliary epithelial cells and hepatocytes did not express monokine genes. No marker of immune activation other than monokine gene expression was detected in these histologically normal livers. The expression of the IL-1 beta gene and of the IL-6 gene may be induced by gut-derived LPS, and could play a role in the modulation of hepatocyte function in normal liver.

Gene Expression↗
PubMed1992

Reinfection of liver graft by hepatitis C virus after liver transplantation.

We have investigated hepatitis C virus (HCV) viremia before and after orthotopic liver transplantation (OLT). 38 patients were examined; 16 were anti-HCV positive and 22 anti-HCV negative pre-OLT in a RIBA-2 test (Ortho Diagnostic Systems Inc., Westwood, MA). HCV-RNA was detected using a modified nested polymerase chain reaction in 14/38 and 10/38 patients before and after OLT, respectively. 7 of these 14 subjects who were HCV-RNA positive before OLT were also positive for serum hepatitis B surface antigen. After OLT, six patients became HCV-RNA positive, likely as a result of transfusions, while four developed a probable recurrence of HCV infection. Infection of the liver graft by the same strain of HCV was indeed demonstrated by sequence analysis of a hypervariable domain (in the envelope region) in two cases. This establishes the possibility of HCV recurrence and shows the usefulness of polymerase chain reaction as the only assay currently capable of identifying HCV infection after OLT.

Base Sequence↗
PubMed1992

The Paul Brousse liver transplant series 1989 to 1992: new trends in the last four years.

In the last four years, 551 liver transplantations have been performed at the Paul Brousse center, for a total of 840 liver transplantations performed from 1984 to 1992. Several changes have been observed in the field of liver transplantation in the past years. The field of immunosuppression was marked mainly by the advent of FK506 as a preventive treatment of rejection and as a treatment of cortico-resistant rejection. Results are still under analysis. From the surgical viewpoint, the main modification was the advent of UW solution, which extends cold ischemic time. However, our policy was to maintain the cold ischemic time at less than 12 hours. Primary indications for liver transplantations have changed with an increase in the rate of patients transplanted for cirrhosis related to hepatitis virus infection: from 24% in the period 1984-1988 to 42% in the period 1989-1992. The difference was due mainly to HCV-related cirrhosis, which increased from 8% to 20%. Alcoholic cirrhosis was a rare indication in the period 1989-1992 (3.4%); however, it was an increasing indication in the last 2 years. In order to improve the long-term results, major attention was given to the recurrence of initial liver disease. In patients transplanted for HBsAg-positive liver disease, long-term passive anti-HBs immunoprophylaxis was administered, which reduced the rate of HBV recurrence in patients without HBV replication before transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Academic Medical Centers↗
PubMed1992

[Kaposi's sarcoma following liver transplantation].

A 54-year-old man developed Kaposi's sarcoma 2 months following orthotopic liver transplantation for hepatitis B-associated liver cirrhosis. At that time he was on combined immunosuppressive therapy (azathioprine, prednisone and cyclosporine A). The disease is very prevalent among immunosuppressed patients following renal transplantation, but is considered to be relatively rare following liver transplantation. The patient ran a relatively benign course without organ involvement and with only the skin disease. This is the first case of Kaposi's sarcoma following liver transplantation reported in Israel.

Humans↗
PubMed1992

[Pregnancy after hepatic transplantation. 17 pregnancies].

The number of orthotopic liver transplantations (OLT) is increasing and longterm survival is improving. More women recipients may choose to become pregnant. We report a one-center experience with the course and outcome of 17 pregnancies in 17 liver transplant out of 675 OLT since 1985. 10 women delivered of 10 healthy infants at 38 +/- 1.5 week's gestation. There was no preterm delivery and the mean birth weight was 2.990 +/- 370 g, birth weight was adequate for gestational age in any case. Four cesarean sections were performed for obstetrical indications. No congenital anomalies occurred in the children. Hypertension occurred in 2 out of twelve patients and appeared as the main complication to deal with. There was one case with graft function impairment at 37 weeks' gestation. One uncomplicated pregnancy is ongoing at 29 weeks' gestation. There were 4 spontaneous and 2 therapeutic abortions for impaired liver function. Pregnancy is successful in a large proportion of these patients but must be planned and managed as high-risk situations by an obstetrician and a specialist of the liver transplant. Pregnancy should be advised against in patients with poor liver function or active viral infection; a 12 months interval from OLT to pregnancy is since to be the minimal requirement. Post-transplant immunosuppressive therapy consisted of azathioprine, corticosteroids and ciclosporin A, and was maintained throughout pregnancy. Genetic counselling should be provided when the primary liver disease is inherited. This being said, as shown by the results of our study and those reported in the literature, pregnancy is not only feasible but also successful in a large proportion of OLT recipients.

Abortion, Spontaneous↗
PubMed1991

[Liver transplantation in non-alcoholic cirrhosis in adults].

Liver transplantation has become the treatment of end-stage cirrhosis. The results of transplantation should be improved by a better knowledge of prognostic criteria in cirrhosis, which would help in timing the transplantation, and by a better prevention of graft reinfection with hepatitis viruses.

Adult↗
PubMed1991

Passive immunoprophylaxis after liver transplantation in HBsAg-positive patients.

110 HBsAg-positive patients underwent orthotopic liver transplantation and received long-term anti-hepatitis B virus (HBV) passive immunoprophylaxis with anti-HBs immunoglobulin. During a mean follow-up period of 20 months, all patients became HBsAg negative after transplantation but circulating HBsAg reappeared in 25 (22.7%). Overall 1-year survival was 83.6% and overall 2 year actuarial recurrence of HBsAg was 29% (59% after posthepatitis B cirrhosis, 13% after posthepatitis B-delta cirrhosis, and 0% after fulminant hepatitis B). Patients with HBV cirrhosis who were HBV-DNA positive had a much greater risk of HBsAg recurrence than patients who were HBV-DNA negative (96% vs 29% at 2 years). Reappearance of HBsAg was associated with evidence of HBV replication and abnormal histological findings in the graft. Long-term passive anti-HBV immunoprophylaxis significantly reduced HBV reinfection and improved survival in patients without evidence of active HBV replication before orthotopic liver transplantation.

Adolescent↗
PubMed1991

[Liver transplantation and the major histocompatibility complex].

We have carried out a retrospective study over 308 liver transplant patients (31 of them have had a retransplantation) in Professor Bismuth's Department at Paul Brousse Hospital. The purpose of the study was a search for the possible effect of donor/recipient major histocompatibility complex on the evolution of the transplantation. We chose to study four parameters: early acute rejection; chronic rejection; retransplantation cases and death frequency; graft survival. We observed the following: for HLA A locus: in cases of total or partial compatibility there are more moderate early acute rejections than in the case of incompatibility (p less than 0.02); for HLA B locus: in the case of total compatibility there are more chronic rejections than in cases of partial or total incompatibility (p less than 0.03); for joint A and B locus: the results are similar to those of A locus (p less than 0.03); for HLA class I: we observed no effect either on graft survival or on retransplantation cases or on death frequency; for HLA DR: we did not find any effect on the studied parameters. Considering the low statistical significance of these results and in order to confirm our analysis, we have started a prospective study in collaboration with two other European Transplantation Centers.

Graft Rejection↗