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Biomedical subjects

M Davis

Publications and source records attributed to M Davis.

At least 559 records · Page 31Linked to original sources
PubMed1981

Strychnine: brainstem and spinal mediation of excitatory effects on acoustic startle.

The present study investigated the effects of the glycine antagonist strychnine on the acoustic startle response in rats. Strychnine (0.25, 0.50, 1.0, 1.25, 1.5 and 2.0 mg/kg) administered intraperitoneally (i.p.) was found to produce a dose-dependent increase in startle amplitude that reached its greatest magnitude within 10-15 min after injection. These doses did not produce convulsions or behavioral activation. In order to localize the site of action of this excitatory strychnine effect, rats were implanted with catheters in the lumbar region of the spinal cord (intrathecal implantation), in the cisterna magna, or in the lateral ventricle and later tested for startle after microinjections of strychnine. Dose-dependent excitatory effects on acoustic startle were found when strychnine was injected onto the spinal cord (3.12-12.5 microgram) or into the cisterna magna (6.25-25.0 microgram), whereas infusion into the lateral ventricle produced inhibition (6.25-25.0 microgram). The peak increases in startle following intrathecal (164%) and intracisternal (144%) strychnine were similar to the increase seen following systemic strychnine (160%). Thus, the excitatory effect of systemic strychnine appears to be mediated in the spinal cord and/or brainstem, consistent with data showing that glycine receptors are primarily localized in the caudal regions of the central nervous system. Furthermore, these results suggest that glycine exerts a tonic inhibitory influence on acoustic startle. The possible relation of such a system to phenomena that involve reduction in startle amplitude (e.g., habituation, pre-pulse inhibition) is discussed.

Acoustic Stimulation↗
PubMed1981

Do women develop alcoholic liver disease more readily than men?

The sudden increase in alcoholic liver disease among women in the past 10 years has caused much speculation that they may be more susceptible to the hepatotoxic effects of alcohol than men. Women tend to present with more severe liver disease, particularly alcoholic hepatitis, and do so after a shorter period of excessive drinking and at a lower daily alcohol intake. Differences in body size and composition are partly responsible for the greater susceptibility of women, but differences in immune reactivity between the sexes may also play a part. Greater emphasis must be placed on designing abstinence programmes specifically for female patients, on earlier detection of liver disease, and on educating women about hazardous drinking levels.

Alcohol Drinking↗
PubMed1981

Factors contributing to mortality in paracetamol-induced hepatic failure.

Fifty patients with fulminant hepatic failure from paracetamol overdose were reviewed retrospectively to determine whether there had been any avoidable delays in treatment with protective agents, or other preventable factors which could contribute to the high mortality. Only nine were admitted to the local hospital early enough (within 12 hours) to benefit from protective agents, and only three of these were treated. Treatment was delayed in two patients while the results of plasma paracetamol concentrations were awaited. Signs of grade 3 hepatic encephalopathy were never found until 72 hours after the overdose, and sudden deterioration in consciousness at an earlier stage was due either to the sedative effects of drugs or to hypoglycaemia, which in one patient went unrecognised for 24 hours. A rapid deterioration in prothrombin time, which became prolonged by at least 25 seconds at 48 hours, preceded the onset of grade 3 encephalopathy, and this is the time at which transfer should be arranged to avoid the danger of brain-stem coning. This occurred more rapidly in those transferred at a later stage of their illness.

Acetaminophen↗
PubMed1981

Spinal modulation of acoustic startle: opposite effects of clonidine and d-amphetamine.

Direct infusion of d-amphetamine (25--400 micrograms) or phenylephrine (12.5--50 micrograms) onto the spinal cord (intrathecal administration) increased acoustic startle amplitude. These effects were blocked by IP injection of the alpha 1-adrenergic antagonist WB-4101, but not the serotonin antagonist cyproheptadine. In contrast, intrathecal administration of clonidine (0.9--12.5 micrograms) markedly depressed startle. This effect was not blocked by IP administration of WB-4101 or cyproheptadine, but was blocked by IP or intrathecal administration of the alpha 2-adrenergic antagonist yohimbine (5 mg/kg), which by itself increased startle. Moreover, intrathecal yohimbine (100 micrograms) attenuated the depressant effect of IP clonidine, indicating that the spinal cord partially mediates the depressant effects on startle after systemic administration of clonidine. Thus clonidine does not behave like an alpha 1-agonist on acoustic startle, even when introduced directly onto the spinal cord. Conditions under which clonidine produces excitatory or depressant behavioral effects are discussed.

Acoustic Stimulation↗
PubMed1981

Antibody diversity: somatic hypermutation of rearranged VH genes.

The immune response to phosphorylcholine in BALB/c mice has been well characterized. Amino acid sequence analyses of heavy-chain variable (VH) regions from 19 myeloma and hybridoma immunoglobulins binding phosphorylcholine show that 10 are identical (the prototype T15 VH sequence) and 9 are distinct variants differing by one to eight residues. A T15 VH DNA probe was used to isolate four closely related members of the T15 VH gene family, including one encoding the T15 VH sequence, from a sperm genomic library. A comparison of the protein and germline VH sequences suggested that most of the immune response to phosphorylcholine is derived from the T15 germline VH gene segment. The variant heavy chains from the M167 and M603 alpha immunoglobulins differ in their VH protein sequences from T15 by eight and three residues, respectively. We analyzed the somatic variability in and around the coding regions of these two variant VH genes by comparing them with the corresponding regions of the appropriate germline gene segments. The somatic variation has three properties: it is extensive and is found in flanking as well as coding sequences (for example, at least 44 substitutions for the M167 sequence and 10 substitutions for the M603 sequence); in the coding regions, it includes many silent as well as replacement substitutions; and it is focal in nature and centered around the rearranged VH genes. Although the mutations extend into the neighboring upstream and downstream flanking sequences, sequences approximately 5 kb upstream and downstream from the VH genes show no substitutions. Moreover, the associated heavy-chain constant genes (C alpha) from both variant alpha genes are unaltered, indicating that a closely linked and coexpressed gene is unmutated. We conclude that this somatic variation is generated by a special hypermutational mechanism highly localized in its site of execution and highly restricted in its time of operation during B-cell development.

Animals↗
PubMed1981

Hepatic damage after exposure to halothane in medical personnel.

Two surgeons, in whom liver damage developed after occupational exposure to sub-anaesthetic doses of halothane, were found to have a circulating antibody which reacted specifically with halothane-altered hepatocyte membrane components. This antibody had been found previously only in those patients in whom severe hepatic necrosis developed after exposure to halothane and in no other form of liver injury. It may provide a specific diagnostic marker in patients in whom there are other possible causes of liver damage and could, therefore, remove the need for a challenge exposure and its attendant risks.

Adult↗
PubMed1981

Pseudocoarctation of the aorta.

A case of pseudocoarctation of the thoracic aorta manifested by a mediastinal mass on a roentgenogram of the chest and subsequently evaluated with computed tomography (CT) is presented. The following combination of CT findings is thought to be diagnostic of this rare congenital anomaly: (a) demonstration that the mass is part of the aorta, (b) the depiction of the unusual aortic arch high in the mediastinum, (c) visualization of the isthmus portion of the descending aorta not adjacent to the spine but rather located ventral to it and surrounding by aerated lung, and (d) more caudal origin of the subclavian artery resulting in a vascular shadow posterior to the kinked aortic arch.

Aorta, Thoracic↗
PubMed1981

Oxidative metabolism of halothane in the production of altered hepatocyte membrane antigens in acute halothane-induced hepatic necrosis.

Previous investigations have shown that patients with fulminant hepatic failure after halothane anaesthesia have a circulating antibody which reacts with an antigen present on the surface of halothane-altered hepatocytes. In the present study, it has been shown that the expression of the antigen is associated with the oxidative metabolism of halothane, in contrast with results of other groups which have shown that the reductive route is involved in the direct hepatotoxic reaction attributed to halothane.

Animals↗
PubMed1981

Protein turnover in acute and chronic liver disease.

The method of constant infusion of U14C tyrosine tracer was used to measure whole body protein turnover in 24 patients with liver disease of varying severity. Whilst on a basic diet of glucose alone (5 g/hr), protein turnover and endogenous breakdown was significantly elevated in patients with cirrhosis and fulminant hepatic failure (F.H.F.), breakdown rising to 700 g/d greater than normal in F.H.F. In addition plasma aromatic aminoacids were significantly elevated and positively associated with the increases in endogenous protein breakdown (r = 0.78, p less than 0.05). Fourteen patients had a second infusion after dietary supplementation with either complete aminoacids (3 g/hr, n = 8) or branched chain aminoacids (BCAA, 4 g/hr, n = 6). The complete mixture did not worsen encephalopathy, improved the plasma aminoacid pattern, reduced protein breakdown and resulted in positive aminoacid balance. The BCAA supplements significantly reduced protein oxidation and endogenous breakdown. The results indicate that protein restriction in cirrhosis and fulminant hepatic failure will not significantly affect the load of aminoacids on the liver, nor their accumulation in plasma. Nutritional support of such patients should therefore include 40 - 60 g. protein per day to prevent protein depletion, and hypertonic glucose and insulin to suppress catabolism. BCAA supplementation may play a useful supportive role in increasing the utilisable nitrogen content of the diet and further suppressing catabolism.

Acute Disease↗
PubMed1981

Controlled clinical trial of a new non-calorigenic sweetening agent.

In a controlled trial of a double-blind cross-over design, it has been shown that "Marvie', a non-calorigenic sweetener containing 58 per cent maltitol by weight, is an effective sweetener which has no influence on routine haematological and biochemical parameters. The dose that could be tolerated without undesirable symptoms was between 20 and 30 g per day. Above this dose, flatus production with abdominal discomfort could limit tolerance to this sweetening agent.

Adult↗
PubMed1981

Use of liver function tests as predictors of rifampicin metabolism in cirrhosis.

Normal subjects taking rifampicin regularly, show a fall in serum and urinary drug concentrations from enzyme induction and increased biliary excretion. In cirrhosis, hepatocellular dysfunction and impaired biliary excretion may prevent these changes, but there is little information on how the drug should be prescribed in such patients. Serum and urinary rifampicin concentrations were therefore measured in thirteen patients and five controls during a seven-day course (600 mg/day). In controls, peak serum concentrations on Day 7 were lower than on Day 1 (7.0 +/- 3.0 and 8.0 +/- 1.0 microgram/ml respectively) and this was also the case for nine cirrhotic patients with mild impairment of liver function (6.0 +/- 1.0 and 11.0 +/- 2.0 microgram/ml (p less than 0.02). In both groups there was an accompanying fall in urinary rifampicin excretion due to a decrease in desacetylrifampicin excretion. In the remaining four cirrhotic patients, peak serum rifampicin levels rose from 11.0 +/- 5.0 to 17.0 +/- 6.0 microgram/ml and urinary excretion of desacetylrifampicin did not fall. Although values for serum albumin and prothrombin time were of limited value in predicting drug accumulation, pretreatment levels of bilirubin exceeding 50 mumol/l were present in all four patients showing an increase in serum rifampicin concentration. Furthermore, only in this group was there a rise in serum bilirubin during treatment, almost certainly the result of competition between rifampicin and bilirubin for hepatic uptake and excretion. In all patients with cirrhosis, bilirubin concentrations exceeding 50 mumol/l should be an indication for reduction of rifampicin dosage.

Drug Administration Schedule↗
PubMed1980

Halothane hepatitis.

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Chemical and Drug Induced Liver Injury↗
PubMed1980

Malnutrition and immuno-incompetence in patients with liver disease.

The incidence of malnutrition and immunocompetence in 156 patients admitted to hospital with liver disease was investigated. Expected weight/height was within the normal range for all groups except those with carcinoma. Triceps skinfold thickness (TSF) was reduced in 49% of patients with cirrhosis and 55% with alcoholic disease. Hypoalbuminaemia was common in all groups, with 66% of those with chronic disease having concentrations below 35 g/dl. Lymphopenia was equally common, 65% of patients with fulminant hepatic failure (FHF) having counts below 1000 cells/mm3. Incidence of total anergy to standard skin tests was 54% overall: 93% in FHF and 60% in cirrhosis and alcoholic disease. There were significant links between reduced TSF and hypoalbuminaemia, lymphopenia and anergy, hypoalbuminaemia and anergy, and anergy and mortality. Reduced TSF was only associated with anergy in patients with chronic disease. The high incidence of immuno-incompetence may underlie the frequent occurrence of spontaneous infections in patients with liver disease, and the association between anergy and malnutrition in patients with chronic liver disease suggests that the anergy may be partly reversible by dietary measures.

Body Weight↗