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Biomedical subjects

D F Schafer

Publications and source records attributed to D F Schafer.

At least 19 recordsLinked to original sources
PubMed1991

gamma-Aminobutyric acid localization and function as modulator of cholinergic neurotransmission in rat antral mucosal/submucosal fragments.

gamma-Aminobutyric acid, a neurotransmitter in the central nervous system, has been shown to be present in and synthesized and secreted by rodent and feline myenteric plexus neurons. The aims of the present studies were to measure gamma-aminobutyric acid concentrations and synthesis and to establish cellular localization and uptake of gamma-aminobutyric acid by immunocytochemistry and autoradiography, respectively, within mucosal and submucosal tissues of the rat antrum. Direct demonstration of [3H]gamma-aminobutyric acid release and the effects of exogenous gamma-aminobutyric acid and muscimol, a GABA alpha agonist, on [3H]acetylcholine release from antral mucosal/submucosal fragments were examined in perifusion experiments. gamma-Aminobutyric acid content and synthesis, as reflected by glutamic acid decarboxylase activity, were present within antral mucosa at levels two to three times that of the body and muscular layers of both the gastric body and antrum. gamma-Aminobutyric acid was identified immunocytochemically, principally in mucosal epithelial cells of the antrum. Exogenous gamma-aminobutyric acid and muscimol were capable of stimulating acetylcholine release through a GABA alpha receptor-mediated mechanism that was abolished by tetrodotoxin. These results indicate that gamma-aminobutyric acid is present in and taken up by epithelial cells of the gastric antrum and that gamma-aminobutyric acid is capable of being synthesized by antral mucosal/submucosal tissues. Furthermore, these studies suggest that a peripheral gamma-aminobutyric acid mechanism that may modulate cholinergic neurotransmission and endocrine cell function exists within the antrum.

Acetylcholine↗
PubMed1990

Sjögren's syndrome in patients with primary biliary cirrhosis.

Symptomatology and objective findings of Sjögren's syndrome were evaluated in 38 consecutive patients with primary biliary cirrhosis. Symptoms of Sjögren's syndrome were present in 18 (47.4%) patients, but were severe enough to warrant therapy in only four (10.5%). Nineteen patients consented to evaluation for Sjögren's syndrome, which included Schirmer's I test, measurement of parotid flow rate and serum autoantibodies, labial minor salivary gland biopsy and human leukocyte antigen typing. Histological changes diagnostic of Sjögren's syndrome were present in five patients (26.3%). All five patients had symptoms of Sjögren's syndrome and three had abnormal Schirmer's I tests, but none had corneal ulcerations or decreased parotid flow rates. Results of serological tests and human leukocyte antigen typing were not similar to those described in patients with primary Sjögren's syndrome but were similar to those described in patients with rheumatoid arthritis and Sjögren's syndrome. These findings indicate that Sjögren's syndrome associated with primary biliary cirrhosis is a form of secondary Sjögren's syndrome resembling that associated with rheumatoid arthritis.

Aged↗
PubMed1990

The effect of age on the relative potency of midazolam and diazepam for sedation in upper gastrointestinal endoscopy.

Diazepam and midazolam are considered safe and effective sedative agents for diagnostic procedures. However, there have been recent reports of deaths in older patients receiving midazolam for sedation. We examined the relative potency of diazepam compared with midazolam as a function of age in two large groups of patients receiving intravenous benzodiazepines for upper gastrointestinal endoscopy. While midazolam and diazepam are approximately equivalent before age 60, after age 60 the relative potency of midazolam compared with diazepam increases markedly. The rapid decline in dose necessary to sedate older patients with midazolam may explain deaths occurring in older patients who have received this drug. Until this problem receives definitive study, we advise that diazepam be preferred over midazolam for intravenous sedation in patients over 60.

Adult↗
PubMed1989

Fulminant hepatic failure and orthotopic liver transplantation.

1. Twenty-four patients were transplanted for fulminant hepatic failure at the University of Nebraska Medical Center from 1986 (July) to 1988. Long-term survival is about 58%. 2. FHF is an increasingly common indication for liver transplantation. 3. Cerebral edema, organ availability, and late referral are obstacles to improved survival. 4. Randomized trials have not been performed to demonstrate that transplantation is superior toother therapies. For some etiologies, such as acute Wilson's disease, in which mortality is 100%, transplantation is clearly indicated. For other etiologies, such as acetaminophen-induced FHF, in which clear gains in survival have been shown using more conservative therapies, the decision to transplant patients becomes more difficult. As all forms of therapy improve, all patients will benefit.

Adolescent↗
PubMed1988

In-hospital mortality as a function of body mass index: an age-dependent variable.

In a retrospective review of 8428 hospital admissions, the relationship between age, sex, disease category, body mass index, and mortality during hospitalization was examined. Records were analyzed for adult admissions whose principal diagnosis fell into one of three categories: malignant disease, heart and cerebrovascular disease, and other diseases. In this study, age, disease category, and body mass index were predictors of survival; sex and race were not. Predicted mortality calculated by logistic regression was greatest at the extremes of body weight in all age groups and in each disease category describing a U-shaped relationship. Obesity was associated with higher mortality only when subjects were 100% or more overweight, whereas being at or below ideal weight was usually associated with increased mortality. Lowest mortality occurred at moderate overweight. The deleterious effects of extremes of body weight take on increasing importance the older the age of the patient. Underweight seems to be a more important predictor of mortality than overweight in older hospitalized subjects. The higher mortality in thin patients could not be explained by weight loss between hospitalizations.

Adult↗
PubMed1988

Changes in cerebral receptors for gamma aminobutyric acid in patients with hepatic encephalopathy.

If the gamma-aminobutyric acid (GABA) inhibitory neurotransmitter system plays an important role in the mediation of hepatic encephalopathy (HE) in man, changes in the status of receptors for GABA in the brain may occur in patients with HE. To test this possibility, brains were obtained at autopsy from 11 patients who had died of causes unrelated to liver disease and from 11 patients who had died with chronic liver disease. Eight of the liver disease group had overt HE at the time of death. The specific binding of GABA to synaptic membranes isolated from frontal cortex was determined. Mean specific binding of GABA for patients with cirrhosis without overt HE was similar to that for control patients. In contrast, corresponding means for patients who had mild HE (stages I-III) and for patients who had severe HE (stage IV) were 45% higher (p less than 0.05) and 43% lower, respectively, than that for control patients. The mean specific binding of GABA was significantly greater for patients with mild HE than in patients with severe HE (p less than 0.025). Scatchard plots of the GABA binding data were curvilinear and consistent with a model of GABA receptors with two independent binding sites. Computer-assisted analysis of the binding data indicated that the altered GABA binding observed in patients with HE is attributable to changes in the affinity rather than the density of both GABA receptors (increased affinities in mild HE, and decreased affinities in hepatic coma). These findings are compatible with the hypothesis that alterations in GABAergic neurotransmission are associated with and contribute to the syndrome of HE in man.

Aged↗
PubMed1986

Randomized trial of chlorambucil for primary biliary cirrhosis.

Twenty-four patients with primary biliary cirrhosis were entered into a prospective, randomized trial of chlorambucil therapy. Thirteen patients received chlorambucil (0.5-4 mg/day) and 11 patients received no therapy; all have been followed for 2-6 yr (mean, 4.1 yr). Two control but no treated patients died. Average serum bilirubin, serum aspartate aminotransferase activities, and albumin levels improved or remained unchanged in treated patients but worsened in controls. Serum alkaline phosphatase levels did not change in either group. Immunoglobulin M levels decreased and became normal in all treated patients but in only 3 control patients. Liver biopsy histology revealed an improvement in inflammatory cell infiltrate in treated patients in comparison with controls, but no significant change in degree of fibrosis or the histologic stage of disease. Side effects of therapy included bone marrow suppression necessitating discontinuation of the drug in 4 patients. These findings indicate that chlorambucil therapy may retard the progression of primary biliary cirrhosis. Whether such therapy will ultimately decrease morbidity and improve survival in this disease can only be demonstrated by large-scale, placebo-controlled trials.

Adult↗
PubMed1986

Selective immunoglobulin A deficiency associated with primary biliary cirrhosis in a family with liver disease.

A family is described in which multiple members are afflicted with liver disease and primary biliary cirrhosis (PBC). In the third generation, one member died of PBC, and a second individual has both symptomatic PBC and selective immunoglobulin A (IgA) deficiency, an association not previously reported. By culturing this patient's lymphocytes in vitro it was shown that the IgA deficiency was due to a failure of B cells to secrete IgA. Two other siblings of this patient have multiple serum biochemical and serologic abnormalities that are sometimes associated with PBC, but they do not have histopathologically overt PBC or IgA deficiency. All three surviving family members have a diminished autologous mixed lymphocyte reaction, an immunologic abnormality that has previously been found in patients with PBC, selective IgA deficiency, and several autoimmune diseases. As there is an association between selective IgA deficiency and certain autoimmune diseases, it is possible that this immunodeficiency contributed to the development of PBC in the patient in whom the two diseases coexisted. Furthermore, the occurrence of PBC in a patient with selective IgA deficiency indicates that the pathogenesis of PBC does not require IgA-dependent immune mechanisms.

Aged↗
PubMed1986

Adequate diet prevents hepatic coma in dogs with Eck fistulas.

The conventional animal model of human portal systemic encephalopathy is the dog with Eck fistula. Dogs fed standard dog chow after Eck fistula manifest anorexia, weight loss, hepatic atrophy and encephalopathy. This study was done to determine the natural history of dogs undergoing Eck fistulas when adequate nutrition is maintained with a palatable diet. Twenty-four mongrel dogs were divided into four groups--Eck fistula fed standard dry dog chow (EF-SC) (n equals nine); sham operated fed standard chow (SO-SC) (n equals five); Eck fistula fed a liquid (Isocal) diet (EF-LD), LD), and sham operated fed a liquid diet (SO-LD) (n equals five). Dogs were sacrificed when they had clinical signs of encephalopathy or up to 120 days after operation. EF-SC dogs had a daily caloric intake approximately 40 per cent of that of the other groups. Two EF-SC dogs died of sepsis within two weeks of the operation, the other seven became encephalopathic between 46 and 91 days (a mean of 63.6 +/- 15.6). No other dogs had signs of neurologic deterioration. EF-SC dogs lost 19 +/- 9 per cent body weight and the serum albumin level decreased 14.5 per cent while the other groups maintained body weight and serum albumin levels. Both EF-SC and EF-LD groups had decreased liver weight to body weight ratios (LW X 100/BW) compared with sham operated upon dogs reflecting hepatic atrophy (1.97 +/- 0.7 and 2.2 +/- 0.23 versus 3.04 +/- 0.85 and 3.48 +/- 0.44). Results of histologic examination of the liver revealed hepatocyte atrophy, deglycogenation and lipid accumulation in EF dogs. We conclude from these data that providing dogs with Eck fistula a palatable diet prevents weight loss and malnutrition, but not hepatic atrophy. The lack of neurologic signs in well nourished dogs suggests to us that data concerning hepatic coma from the standard Eck fistula model should be interpreted with extreme caution.

Animals↗
PubMed1985

gamma-Aminobutyric acid plasma levels and brain binding in Eck fistula dogs.

It has been hypothesized that gamma-aminobutyric acid (GABA), the principle inhibitory neurotransmitter of the mammalian brain, contributes to the neural inhibition of hepatic encephalopathy. Eck fistulae were created in seven dogs and celiotomy alone performed in five dogs to determine plasma GABA levels, brain GABA binding, and synaptic membrane changes in dogs after creation of Eck fistulae. Eck fistula dogs lost 19 +/- 9% body weight, lost hair, ate poorly, and developed atrophic livers with classic hepatic histological changes. Control dogs maintained body weight, normal behavior, and normal liver histology. Plasma GABA levels were elevated significantly in the Eck fistula dogs (312 +/- 105.9 nM) both as compared to controls (154.4 +/- 69.8) and to preoperative levels (161.6 +/- 56.7, P less than 0.05). Brain GABA binding for animals sacrificed at 6-9 weeks was not statistically different from sham-operated dogs sacrificed at 6 weeks (1.87 +/- .54 pmole/mg protein vs 1.186 +/- 24, P less than 0.2). Synaptic membrane fluidity and cholesterol were likewise unchanged. Plasma GABA levels are increased significantly following complete portal diversion but do not correlate with the degree of encephalopathy. GABA binding to neural membranes are not significantly increased in Eck fistula dogs. These findings do not support a direct relationship between plasma GABA levels and neurologic impairment in Eck fistula dogs.

Animals↗
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↗