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S C Pappas

Publications and source records attributed to S C Pappas.

34 records · Page 2Linked to original sources
PubMed1985

Treatment of chronic non-A, non-B hepatitis wih acyclovir: pilot study.

Five patients with chronic non-A, non-B hepatitis were entered into a pilot therapeutic study of the antiviral agent acyclovir [9-(2-hydroxyethoxymethyl)guanine]. Each patient received acyclovir by slow intravenous infusion in a dosage of 5 mg/kg every 8 hr for 10 days. During therapy, serum aminotransferase levels decreased by more than 50% in two patients, remained unchanged in two patients, and rose (by 32%) in the final patient. The two patients whose serum aminotransferase levels decreased during acyclovir treatment subsequently received a second course of drug using a higher dose (10 mg/kg every 8 hr for 10 days). Serum aminotransferase levels rose in both patients (by 54% and 121%) during the second course of therapy. Acyclovir was well tolerated in these patients, and there were no symptoms or signs attributable to drug toxicity during or after treatment. During a subsequent 12-month follow-up period, none of the five patients has manifested either a clinical or serum biochemical improvement in their chronic liver disease. Spontaneous fluctuations in serum aminotransferase levels unrelated to acyclovir therapy were noted in three of the five patients. These findings suggest that a short course of acyclovir does not have any appreciable long-term beneficial effect on the course of chronic non-A, non-B hepatitis.

Acyclovir↗
PubMed1985

Treatment of chronic type B hepatitis with multiple ten-day courses of adenine arabinoside monophosphate.

Ten patients with chronic type B hepatitis were treated with three courses of adenine arabinoside monosphosphate (Ara-AMP). The drug was given intramuscularly at a dosage of 10 mg/kg/day in ten-day courses during each of three sequential months. The patients were all men, aged 31-61 years, who were known to have had chronic hepatitis for one to four years. Each of the ten-day courses of Ara-AMP was accompanied by a marked inhibition in the serum levels of hepatitis B virus (HBV) DNA and DNA polymerase activity. However, HBV-DNA remained detectable in every patient during treatment and invariably rebounded to pretreatment levels soon after each course was stopped. One patient developed severe, and two patients developed mild neuromuscular side effects. During a 12-18-month follow-up period, only one of the ten patients has had a sustained clinical, serum biochemical, and serological remission. In this patient, serum HBeAg, HBV-DNA, and DNA polymerase became undetectable three months after the final course of treatment; serum aminotransferase levels subsequently fell into the normal range; and a follow-up liver biopsy showed a diminution in the chronic inflammatory cell activity and a disappearance of intrahepatic hepatitis B core antigen reactivity. Thus, multiple ten-day courses of Ara-AMP do not induce a high rate of remissions in this disease and are associated with appreciable neuromuscular toxicity. Ara-AMP is a potent inhibitor of serum levels of hepatitis B virus, but Ara-AMP therapy has not been shown to have long-term beneficial effects in chronic type B hepatitis.

Adult↗
PubMed1984

Enzymes of cerebral GABA metabolism and synaptosomal GABA uptake in acute liver failure in the rabbit: evidence for decreased cerebral GABA-transaminase activity.

Measurements of the activities of the two key enzymes in cerebral GABA metabolism--glutamate decarboxylase (GAD) and GABA-transaminase (GABA-T)--were performed in normal rabbits and in rabbits with hepatic encephalopathy due to galactosamine-induced liver failure. Furthermore the uptake of GABA by synaptosomes was studied. Hepatic encephalopathy was associated with a marked decrease in the activity of GABA-T. This decrease in activity was already apparent in galactosamine-treated rabbits before the onset of hepatic encephalopathy. Sera and serum ultrafiltrates of rabbits with hepatic encephalopathy but not of normal rabbits or of rabbits with uremic encephalopathy were shown to inhibit GABA-T activity in vitro. Cerebral GAD activity and synaptosomal GABA uptake in rabbits with hepatic encephalopathy and in untreated animals were not different. These later findings indicate that hepatic encephalopathy is not associated with alterations of presynaptic GABA nerve terminals in the central nervous system. The demonstration of a decrease in cortical GABA-T activity provides indirect evidence for decreased GABA turnover in the brains of rabbits with hepatic encephalopathy and thus is compatible with augmented GABA-ergic inhibitory neurotransmission contributing to the neural inhibition of hepatic encephalopathy.

4-Aminobutyrate Transaminase↗
PubMed1984

[Pathogenesis of hepatic encephalopathy--studies in the rabbit model of acute liver failure].

In rabbits the administration of neither ammonia, nor a mixture of ammonia, a mercaptan and a fatty acid reproduces the changes in visual evoked potentials that occur in galactosamine-induced hepatic coma. The abnormal pattern of visual evoked potentials in galactosamine-induced hepatic coma can be reproduced by administering drugs which induce activation of the gamma-aminobutyric acid (GABA) neurotransmitter system. Also in rabbits the administration of ammonia does not reproduce the changes in receptors for glutamate and GABA in the brain that occur in galactosamine-induced hepatic coma. Galactosamine-induced hepatic coma is not associated with any functionally significant changes in the molecular components of the postsynaptic dopamine receptor. These findings provide no support for the hypotheses of the pathogenesis of hepatic encephalopathy that implicate ammonia, the synergistic action of ammonia, mercaptans and fatty acids or false neurotransmitters. However, these findings are entirely consistent with activation of the GABA neurotransmitter system contributing to neural inhibition in hepatic encephalopathy.

Ammonia↗
PubMed1984

Randomized controlled trial of adenine arabinoside monophosphate for chronic type B hepatitis.

Twenty patients with chronic type B hepatitis were entered into a randomized, controlled study of adenine arabinoside monophosphate. Before entry, all patients were documented to have stable levels of hepatitis B surface antigen, hepatitis B e antigen, serum hepatitis B virus deoxyribonucleic acid, and deoxyribonucleic acid polymerase activity. Ten patients received adenine arabinoside monophosphate and 10 received no treatment. The two groups were well matched with respect to age, sex, known duration of hepatitis B surface antigen, presence of symptoms, serum aminotransferase levels, and hepatic histopathology. During the 4 wk of therapy, serum levels of hepatitis B virus fell dramatically. However, serum hepatitis B virus-deoxynbonucleic acid or deoxyribonucleic acid polymerase activity, or both, remained detectable, and levels of hepatitis B virus invariably rose once therapy was stopped. From 2 to 9 mo after therapy, 4 of the 10 treated patients became hepatitis B e antigen or hepatitis B virus-deoxyribonucleic acid and deoxyribonucleic acid polymerase negative, or both, and the results of routine serum biochemical tests improved. However, 2 of these 4 patients later relapsed. In the control group, 2 patients became seronegative for hepatitis B virus-deoxyribonucleic acid and deoxyribonucleic acid polymerase and manifested improvement in serum biochemical results by 18-24 mo after randomization. Thus, long-term improvements in clinical and serologic features of disease occurred in 20% of both treated and control patients. Side effects of adenine arabinoside monophosphate therapy were common, and 3 patients developed a severe and prolonged neuropathic pain syndrome. These results suggest that a 4-wk course of adenine arabinoside monophosphate therapy does not induce an increased rate of long-term remissions in chronic type B hepatitis.

Adult↗
PubMed1984

Visual evoked potentials in a rabbit model of hepatic encephalopathy. I. Sequential changes and comparisons with drug-induced comas.

The recording of visual evoked potentials in rabbits has been shown to be an objective, reproducible, noninvasive technique for quantitating changes in the pattern of cerebral neuronal activity. The development of hepatic encephalopathy due to galactosamine-induced fulminant hepatic failure was consistently associated with a series of distinctive changes in the visual evoked potential waveform. The pattern of the visual evoked potential in hepatic coma (due to galactosamine-induced fulminant hepatic failure) differed fundamentally from that in ether-induced coma, but was identical to that in comas induced by three drugs which activate gamma-aminobutyric acid-ergic neural mechanisms: pentobarbital, diazepam, and muscimol. These findings are compatible with activation of the gamma-aminobutyric acid inhibitory neurotransmitter system contributing to cerebral neuronal inhibition in hepatic coma due to galactosamine-induced fulminant hepatic failure.

Animals↗
PubMed1984

Visual evoked potentials in a rabbit model of hepatic encephalopathy. II. Comparison of hyperammonemic encephalopathy, postictal coma, and coma induced by synergistic neurotoxins.

To assess neuronal mechanisms of potential importance in the pathogenesis of hepatic encephalopathy, visual evoked potentials were recorded in rabbits with acute hyperammonemic encephalopathy, postictal coma, and toxin-induced coma resulting from the administration of a combination of subcoma doses of three neurotoxins: ammonia, dimethyldisulfide, and octanoic acid. The patterns of visual evoked potentials in these three syndromes were compared with those of rabbits with hepatic encephalopathy due to galactosamine-induced fulminant hepatic failure. In the absence of seizures, the patterns of visual evoked potentials associated with hyperammonemic encephalopathy and toxin-induced coma were fundamentally different from those associated with any stage of hepatic encephalopathy due to galactosamine-induced fulminant hepatic failure. In contrast, the pattern of visual evoked potentials in early postictal coma induced by four different precipitating factors (including toxin-induced seizures) resembled that of late-stage hepatic encephalopathy due to galactosamine-induced fulminant hepatic failure. These findings suggest that the recording of visual evoked potentials may be of value in experimentally testing hypotheses of the pathogenesis of hepatic encephalopathy due to fulminant hepatic failure. They indicate that acute hyperammonemia is not a satisfactory model of hepatic encephalopathy due to galactosamine-induced fulminant hepatic failure, that the occurrence of seizures may lead to incorrect interpretation of experimental data from models of hepatic encephalopathy, and that the syndromes of hepatic encephalopathy due to galactosamine-induced fulminant hepatic failure and postictal coma may share similar neural mechanisms. Finally, the results of this study do not support the hypothesis that hepatic encephalopathy due to galactosamine-induced fulminant hepatic failure is mediated by the synergistic interaction of ammonia, mercaptans, and fatty acids on the brain.

Ammonia↗
PubMed1982

Treatment of methanol poisoning with ethanol and hemodialysis.

Twelve cases of methanol poisoning are reviewed. The clinical presentation and biochemical features are described and the results of treatment with alkali, ethanol and dialysis reported. The outcome of methanol poisoning appears to be related more to the interval between the time of ingestion and the start of therapy and to the degree of acidosis than to the initial serum methanol level. Therefore, early and aggressive treatment with bicarbonate and ethanol and subsequent institution of hemodialysis are strongly recommended whenever methanol can be detected in the blood, especially when metabolic acidosis of the anion-gap type is present, when mental or visual disturbances are present, or when more than 30 ml of absolute methanol has been consumed.

Acidosis↗
PubMed1982

Pipetter's thumb.

Explore the source record for details and available documents.

Allied Health Personnel↗
PubMedDate not supplied

Changes in glutamate receptors on synaptic membranes associated with hepatic encephalopathy or hyperammonemia in the rabbit.

The status of the excitatory glutamatergic neurotransmitter system in hepatic encephalopathy has been studied. Synaptic membranes (SM) were prepared from the brains of normal rabbits, hyperammonemic normal rabbits, and rabbits with fulminant hepatic failure. Data on the specific binding of glutamate to SM indicated that fulminant hepatic failure was associated with a decrease in the number of glutamate receptors on SM from cerebral cortex, cerebellum, and particularly the hippocampus, without any associated change in the affinity of these receptors. In contrast, hyperammonemia was associated with an increase in the affinity and no decrease in the number of glutamate receptors on SM from the hippocampus. These findings indicate that the effects of hyperammonemia and fulminant hepatic failure on cerebral glutamate receptors are fundamentally different. The decreased number of glutamate receptors in hepatic encephalopathy might reflect a decreased sensitivity of glutamatergic neurons to glutamate-mediated neural excitation, a phenomenon that could contribute to the neural inhibition of hepatic encephalopathy.

Ammonia↗
PubMedDate not supplied

Changes in the status of neurotransmitter receptors in a rabbit model of hepatic encephalopathy.

It has previously been shown in an animal model of hepatic encephalopathy (HE) that the number of receptors for the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), increases and that the number of receptors for the excitatory neurotransmitter, glutamate, decreases. To determine the functional status of other neurotransmitter systems in HE, measurements were made of the specific binding of other neurotransmitters to synaptic membranes prepared from the brains of normal rabbits and rabbits in HE due to galactosamine-induced acute liver failure. The development of HE was associated with: (i) a decrease in the density (Bmax) of receptors for the two excitatory amino acid neurotransmitters, aspartate and kainic acid; (ii) an increase in the Bmax of both the low and high affinity binding site for strychnine, a marker for the inhibitory neurotransmitter glycine; (iii) a decrease in the affinity (Kd) of receptors for dopamine, and (iv) no appreciable change in either the specific binding of [3H]D-ala2-methionine enkephalinamide or [3H]naloxone, markers for opiate receptors, or in the Bmax or the Kd of receptors for acetylcholine. If it is assumed that the sensitivity of the brain to neurotransmitters varies directly with the density of neurotransmitter receptors, HE may be associated with increased sensitivity to inhibitory amino acid neurotransmitters and decreased sensitivity to excitatory amino acid neurotransmitters. Thus, the observed changes in neurotransmitter receptors in HE afford a feasible pathophysiological basis for the mediation of the neural inhibition of HE.

Animals↗
PubMedDate not supplied

The GABA hypothesis of the pathogenesis of hepatic encephalopathy: current status.

Gamma-aminobutyric acid (GABA), the principal inhibitory neurotransmitter of the mammalian brain, can induce coma. Outside the central nervous system it is synthesized by gut bacteria and catabolized largely in the liver. GABA and its agonists, as well as benzodiazepines and barbiturates, induce neural inhibition as a consequence of their interaction with specific binding sites for each of these classes of neuroactive substances on the GABA receptor complex of postsynaptic neurons. In a rabbit model of acute liver failure: (i) the pattern of postsynaptic neuronal activity in hepatic coma, as assessed by visual evoked potentials, is identical to that associated with coma induced by drugs which activate the GABA neurotransmitter system (benzodiazepines, barbiturates, and GABA agonists); (ii) the levels of GABA-like activity in peripheral blood plasma increase appreciably before the onset of hepatic encephalopathy, due at least in part to impaired hepatic extraction of gut-derived GABA from portal venous blood; (iii) the blood-brain barrier becomes abnormally permeable to an isomer of GABA, alpha-amino-isobutyric acid, before the onset of hepatic encephalopathy; and (iv) hepatic coma is associated with an increase in the density of receptors for GABA and benzodiazepines in the brain. These findings are the bases of the following hypotheses: (i) when the liver fails, gut-derived GABA in plasma crosses an abnormally permeable blood-brain barrier and by mediating neural inhibition contributes to hepatic encephalopathy; (ii) an increased number of GABA receptors in the brain found in liver failure increases the sensitivity of the brain to GABA-ergic neural inhibition; and (iii) an increased number of drug binding sites mediates the increased sensitivity to benzodiazepines and barbiturates observed in liver failure by permitting increased drug effect.

Animals↗