PubMed Health⌕ Search

Biomedical subjects

M L Bassett

Publications and source records attributed to M L Bassett.

13 recordsLinked to original sources
PubMed1990

Increased brain uptake of gamma-aminobutyric acid in a rabbit model of hepatic encephalopathy.

Transfer of the inhibitory neurotransmitter gamma-aminobutyric acid across the normal blood-brain barrier is minimal. One prerequisite for gamma-aminobutyric acid in plasma contributing to the neural inhibition of hepatic encephalopathy would be that increased transfer of gamma-aminobutyric acid across the blood-brain barrier occurs in liver failure. The aim of the present study was to determine if brain gamma-aminobutyric acid uptake is increased in rabbits with stage II-III (precoma) hepatic encephalopathy due to galactosamine-induced fulminant hepatic failure. A modification of the Oldendorf intracarotid artery-injection technique was applied. [3H] gamma-aminobutyric acid, [14C] butanol, and 113mIn-labeled serum protein (transferrin) were injected simultaneously 4 s before decapitation. The ipsilateral brain uptake index of gamma-aminobutyric acid was determined from measurements of the 3 isotopes in 5 brain regions. Uncorrected or simple brain uptake indices of [3H] gamma-aminobutyric acid and [113mIn] transferrin were calculated using [14C] butanol as the highly extracted reference compound. The [113mIn] transferrin data were also used to "correct" the brain uptake index of [3H] gamma-aminobutyric acid for intravascular retention of [3H] gamma-aminobutyric acid. The methodology adopted minimized problems attributable to rapid [3H] gamma-aminobutyric acid metabolism, and slow brain washout and recirculation of the radiolabeled tracers. Both the uncorrected and corrected brain uptake indices of gamma-aminobutyric acid as well as the simple brain uptake index of transferrin were significantly increased in both stage II and III hepatic encephalopathy in all brain regions studied. Moreover, these brain uptake indices were significantly greater in stage III hepatic encephalopathy than in stage II hepatic encephalopathy. These findings indicate that transfer of gamma-aminobutyric acid from plasma to brain extracellular fluid is increased in the model of hepatic encephalopathy studied; hence, they provide support for the hypothesis that plasma-derived gamma-aminobutyric acid may contribute to the neural inhibition of hepatic encephalopathy due to fulminant hepatic failure.

Animals↗
PubMed1988

Could an endogenous benzodiazepine ligand contribute to hepatic encephalopathy?

High affinity recognition sites for benzodiazepines are part of the gamma-aminobutyric acid (GABA) supramolecular complex on the plasma membrane of neurons in the mammalian brain. Synthetic agonist benzodiazepines promote GABA-ergic neurotransmission, and hence the hypnotic and anxiolytic effects of this class of drugs, by binding to these sites. A normal physiological role for these binding sites is unknown, and an endogenous ligand for benzodiazepine receptors has not been definitely identified in normal animals. In animals and human beings with hepatic encephalopathy, however, benzodiazepine receptor antagonists have induced amelioration of the encephalopathy, and an endogenous substance that competitively binds to benzodiazepine receptors has been found in cerebrospinal fluid. These findings suggest that an endogenous ligand for the benzodiazepine receptor with agonist properties contributes to hepatic encephalopathy by promoting GABA-ergic neurotransmission.

Benzodiazepines↗
PubMed1988

Is all genetic (hereditary) hemochromatosis HLA-associated.

1. GH in Australia is significantly associated with the HLA-A3 antigen, which is the only independent marker for the disease (B7 in linkage disequilibrium with A3). 2. The haplotype A3, B7, DR2 is the only one with increased prevalence in this disease, presumably due to its being the predominant haplotype among early immigrants. 3. Exceptions to HLA association in GH are rare and can be explained by: (1) incorrect HLA serotyping, (2) chromosomal recombination, or (3) rare homozygous-homozygous mating. 4. These data are consistent with GH being due to a mutant gene or genes in close proximity to HLA-A. 5. Heavy alcohol ingestion does not lead to expression of hemochromatosis in heterozygous subjects.

Alcohol Drinking↗
PubMed1987

Amelioration of hepatic encephalopathy by pharmacologic antagonism of the GABAA-benzodiazepine receptor complex in a rabbit model of fulminant hepatic failure.

Three separate, but allosterically interacting, sites on the gamma-aminobutyric acid (GABA) supramolecular complex in the brain were pharmacologically blocked in rabbits with hepatic encephalopathy due to galactosamine-induced fulminant hepatic failure to determine whether decreased GABAergic neurotransmission can ameliorate the syndrome of hepatic encephalopathy. Bicuculline (a GABAA receptor blocker), Ro 15-1788 (a benzodiazepine receptor antagonist), or isopropylbicyclophosphate (a chloride channel blocker) consistently induced a transient but unequivocal decrease in the clinical severity of the encephalopathy and also corrected the abnormal pattern of the visual evoked response associated with hepatic encephalopathy. Rabbits with hepatic encephalopathy exhibited increased resistance to the convulsive effects of bicuculline. In encephalopathies induced in rabbits by gamma-vinyl-GABA (an inhibitor of GABA catabolism) or diazepam (a benzodiazepine receptor agonist), abnormalities of the visual evoked response similar to those found in hepatic encephalopathy occurred and were corrected by bicuculline and Ro 15-1788, respectively. These findings suggest that in hepatic encephalopathy due to fulminant hepatic failure (a) there is increased GABAergic tone, (b) an amelioration of encephalopathy can be induced by blockade of GABA or benzodiazepine receptors, (c) benzodiazepine receptor antagonists may be of clinical value in the management of hepatic encephalopathy, and (d) an endogenous substance with GABA potentiating properties may be present in hepatic encephalopathy.

Animals↗
PubMed1985

Cohort study of internal malignancy in genetic hemochromatosis and other chronic nonalcoholic liver diseases.

The risk of hepatocellular carcinoma (HCC) and other internal malignancies was examined in patients with genetic hemochromatosis (GH) by following 208 patients from the time of diagnosis to June 1983 and by comparing the numbers of cancers they developed with expected values constructed from cancer registry incidence data by means of actuarial methods. In addition, cancers occurring in a comparison group of 148 subjects with other chronic nonalcoholic liver diseases (CLD) were determined. Among the GH group, 16 new cases of HCC occurred subsequent to the diagnosis of GH, together with 8 other malignancies. The 16 cases of HCC reflect a 200-fold excess risk, which from all indications represents the first quantitation of the risk of this tumor in GH. There appears to be no increased risk of other malignancies in this disease. Among the CLD group only 1 HCC and 1 other malignancy occurred.

Adolescent↗
PubMed1979

Early detection of idiopathic haemochromatosis: relative value of serum-ferritin and HLA typing.

A study of 18 unrelated families with idiopathic haemochromatosis (I.H.C.) was undertaken to define the relative values of HLA typing and serum-ferritin estimation in the early detection of the disease. Sharing of both HLA haplotypes with the proband indicated a high risk of I.H.C. in siblings; but HLA typing was of limited value in detecting affected offspring. Non-identical HLA indicated a low risk of I.H.C. in both siblings and offspring. The presence of HLA A3 was not clinically useful as a marker for I.H.C., since this antigen was also present in 40% of unaffected relatives. In contrast, the serum-ferritin concentration was elevated in 96% of patients with I.H.C. and in only 5% of unaffected relatives. HLA typing provides some indication of the risk of I.H.C. in first-degree relatives, but the combination of serum-ferritin, serum-iron, and transferrin saturation remains the most reliable screening regimen for early diagnosis of I.H.C.

Adolescent↗
PubMed1979

Colorectal cancer. A study of 230 patients.

Clinical presentation, risk factors, investigations, pathology and treatment were examined in a retrospective review of 230 patients with colorectal cancer. Many patients presented with symptoms not usually associated with colorectal cancer, such as pain in the upper part of the abdomen, and rectal bleeding separate from the stool. Iron deficiency anaemia was an uncommon presentation. Over all, one-third of patients had at least one risk factor for colorectal cancer. Risk factors such as adenomatous polyps and family history of colorectal cancer were more common than inflammatory bowel disease and polyposis coli. Although a delay in diagnosis was recorded in one-quarter of patients, the finding of a negative correlation between duration of symptoms and extent of spread suggests that the length of the symptomatic illness is not an important factor in prognosis. Contrary to surgical and medical teaching, only 43% of cancers were in the rectum and rectosigmoid area, and, hence, within reach of the standard sigmoidoscope. Surgical resection was performed in 76% of patients. Forty-three per cent of patients who underwent surgery developed at least one postoperative complication resulting in a longer stay in hospital.

Adenocarcinoma↗
PubMed1977

Intestinal giardiasis, steatorrhoea and peripheral nerve dysfunction.

Two patients presented with similar peripheral neuropathic symptoms. Muscle denervation was shown by electromyography and muscle biopsy. Motor and sensory nerve conduction studies were normal. Both patients had intestinal giardiasis: 1 had asymptomatic steatorrhoea, and the other had diarrhoea and abdominal pain. Treatment with metronidazole abolished the gastrointestinal symptoms. After a delay of several months the neurological symptoms also gradually improved. No other cause of peripheral neuropathy was apparent on investigation, and the relationship between the intestinal giardiasis and the peripheral neuropathy is discussed.

Adult↗