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Biomedical subjects

I A Bouchier

Publications and source records attributed to I A Bouchier.

At least 19 recordsLinked to original sources

A prospective study of alcoholic liver disease and mortality.

We report the 10-year survival of 510 patients with a histological diagnosis of alcoholic liver disease. Eight centres in Scotland and North England contributed to this study. Information was available on 92% of the initial cohort. Age was important, with each decade increasing mortality by 55%. A highly significant interaction between sex and histology was observed with a marked survival benefit for males with non-cirrhotic alcoholic liver disease, while in cirrhotic subjects the pattern was reversed. Patients with decompensated liver disease had a relative increase in mortality in excess of 86% while the increase in mortality for alcoholic hepatitis, 'active' cirrhosis and 'inactive' cirrhosis were 52%, 57% and 91% relative to fatty liver. Alcohol intake at the time of diagnosis did not influence outcome. This study emphasises yet again the increased mortality rate of individuals abusing alcohol compared with the general population.

Adult

Computerised system for the continuous measurement of azygos venous blood flow.

A computer assisted apparatus for the continuous measurement of azygos blood flow is described. The system was validated in vitro and changes in flow which occur with respiration and Valsalva manoeuvre are illustrated. This apparatus allows real time inspection of flow values which enables changes in flow over short periods to be readily studied.

Azygos Vein

Evidence of hydrogen ion secretion from the human gall bladder in vitro.

Gall bladder bile is more acid that hepatic bile and this has been attributed to bicarbonate absorption by the gall bladder epithelium. The aim of this study was to investigate in vitro the acid base changes that occur across the human gall bladder mucosa. Fresh gall bladder tissue was obtained at cholecystectomy and placed in an Ussing Chamber and perfused with Ringer-Krebs glucose bicarbonate solution. The viability of the gall bladder was assessed by measuring the potential differences across the epithelium and by the morphology of the epithelial cells at the end of the experiments. Aliquots from the solutions were taken at two, 45 and 70 minutes and pCO2, hydrogen ion and bicarbonate concentrations were measured. In the mucosal side of the chamber a consistent and significant decrease was observed from two minutes to 70 minutes in bicarbonate concentration while pCO2 and hydrogen ion concentrations significantly increased. The degree of inflammation correlated well with the ability for acidification, the more inflamed the tissue the less its ability to acidify. When the gall bladder was exposed to amiloride or sodium free solution acidification was abolished in the mucosal side. When tissue metabolism was irreversibly inhibited by exposure to formaldehyde, hydrogen ion concentration and pCO2 were significantly decreased in the mucosal side of the chamber compared with the viable gall bladder. The human gall bladder is capable of secreting acid and this may be an important mechanism for preventing calcium precipitation and gall stone formation.

Bicarbonates

The formation of gallstones.

There are two types of gallstones; cholesterol and pigment or bilirubinate. Cholesterol stones are formed in the gallbladder as a consequence of altered hepatocellular and gallbladder function. Overproduction of cholesterol by the liver is the major metabolic precedent of cholesterol gallstones and this may occur because of obesity, drugs, or other factors. Gallbladder factors which promote stone formation include hypomotility and the secretion of nucleating factors such as mucus glycoprotein. It is possible that both of these two factors are mediated by an increase in the prostaglandin production by the gallbladder mucosa. Pigment stones are either brown or black. Brown stones are formed of calcium bilirubinate and are usually associated with biliary infection. They occur in both the gallbladder and the bile ducts. Black pigment stones are extremely hard bilirubin polymers and are found mainly in the gallbladder. Biliary sludge is a necessary precedent of gallstones. It comprises cholesterol monohydrate crystals, glycoproteins and granules of calcium bilirubinate.

Bilirubin

Portal and systemic hemodynamics and humoral factors in cirrhosis with and without ascites.

The pathogenesis of salt and water retention in cirrhosis remains unclear. Systemic and portal hemodynamic parameters, including cardiac output, portal pressure gradient and systemic vascular resistance, were measured in six patients with untreated ascites and in six patients with hepatic cirrhosis with no history of ascites. Renal blood flow, urinary volume, and humoral factors, including plasma renin, aldosterone, angiotensin II, and urine kallikrein, were measured. Significant differences were seen between the two groups in urine volume, urine sodium and fractional sodium excretion, plasma angiotensin II, and the ratio between plasma renin activity and urinary kallikrein excretion (PRA:UKallV). A strong correlation existed between urinary sodium excretion and the PRA:UKallV ratio. No significant differences were detected between the groups in portal, renal, and systemic hemodynamics. The present results suggest that humoral changes occur early in ascites. Altered relationships between intrarenal hormone systems, such as the renin-angiotensin and kallikrein-kinin systems, may be important in salt and water retention.

Ascites

Regional cerebral blood flow and cognitive function in patients with chronic liver disease.

Subtle impairments of cognitive function may be an important cause of occupational and psychosocial morbidity in patients with chronic liver disease. Correlation of structural brain abnormalities with cognitive deficits has yielded inconsistent results. 10 patients with cirrhotic liver disease were compared with 10 age, education, and intelligence matched control subjects. Neuropsychological assessment revealed significant overall cognitive impairments in cirrhotic patients compared with controls (p = 0.02). Regional cerebral blood flow was measured by single photon emission computed tomography (SPET or SPECT) and showed increased uptake of radiotracer in the right and left posterior parts of the basal ganglia and right occipital lobe, together with reduced uptake in the right anterior cingulate region. The degree of cognitive impairment was directly correlated with functional abnormalities in the basal ganglia and limbic cortex (p less than 0.05). Our results suggest that impaired cognitive status may be associated with abnormalities of regional brain function in patients with chronic liver disease. Since these deficits are clinically inapparent, our findings have important implications for identification and management of patients with chronic liver disease.

Analysis of Variance

The hands in alcoholic liver disease.

Chronic liver disease is frequently associated with a hyperdynamic circulation, with warm hands and capillary pulsations. In our experience, however, a significant number of patients with alcoholic liver disease complain of cold hands. In this study, we have investigated the presence of the subjective feeling of hand temperature in 114 patients with alcoholic liver disease compared with 96 healthy controls, and studied possible correlations of this subjective feeling with the severity of liver disease. Significantly more patients with alcoholic liver disease complained of cold hands than did normals, and these differences were more prominent in the male group. The awareness of cold hands appears to be commoner in an intermediate group of patients, between those with noncirrhotic liver disease without varices and those with cirrhosis with varices. A similar pattern of awareness of hand temperature was found when patients were staged according to the severity of their liver disease. We conclude that a staging can be made; at an early stage of liver disease, patients tend to have warm hands, subsequently develop cold hands, and at a later stage, their hands become warm again.

Adult

Meta-analysis of value of propranolol in prevention of variceal haemorrhage.

A meta-analysis of all controlled clinical trials of beta-adrenoceptor blocking drugs, principally propranolol, in the prevention of primary or secondary variceal bleeding has shown that beta-blockade significantly reduced the occurrence of variceal bleeding, deaths from variceal bleeding, and overall mortality. There was some heterogeneity between trials in the effect of beta blockade on secondary prevention. When only fully reported, randomised, placebo-controlled studies were included the heterogeneity disappeared, and the reductions in bleeding episodes and mortality became more striking. Separate analyses of primary and secondary prevention studies also showed clear reductions in occurrence of variceal bleeding and deaths. These results seem to indicate the value of beta-adrenoreceptor blocking drugs for the primary prevention of haemorrhage from large oesophageal varices. However, there is still a need for large multicentre trials of beta-blockade for primary prevention of variceal bleeding in patients without large varices and of comparisons between beta-blocker therapy with other treatments in secondary prevention.

Adrenergic beta-Antagonists

Gall stones.

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Aged

Skeletal muscle and whole-body protein turnover in cirrhosis.

1. We investigated arteriovenous exchanges of tyrosine and 3-methylhistidine across leg tissue in the postabsorptive state as specific indices of net protein balance and myofibrillar protein breakdown, respectively, in eight patients with cirrhosis and in 11 healthy control subjects. Whole-body protein turnover was also measured using L-[1-13C]leucine. 2. Leg efflux of tyrosine was 45% greater in cirrhotic patients than in normal control subjects [-6.5(1.4 to -19.1) vs -4.2(-2.2 to -7.7) mumol min-1 100 mg-1 of leg, median (range), P less than 0.025]. 3-Methylhistidine efflux was not significantly altered. 3. In cirrhosis, whole-body leucine flux was normal but whole-body leucine oxidation was elevated so that whole-body protein synthesis was depressed by 17%. 4. The results indicate the predominant mechanism of muscle wasting in cirrhosis to be a fall in muscle protein synthesis, which is accompanied by an overall fall in whole-body protein turnover.

Aged

Glutathione S-transferase in human bile.

Glutathione S-transferase (GST) isoenzymes have been measured by specific radioimmunoassay in human bile samples. GST Mu was found in 50% of samples while GST Pi, GST B1 and GST B2 were present in all samples; GST Pi constituted the major isoenzyme identified. The findings of the radioimmunoassay were confirmed by a one-step purification of GST from bile, using affinity chromatography, followed by their identification using sodium dodecyl sulphate-polyacrylamide gel (SDS-PAGE). Inhibition studies showed that, at the concentrations of bile salts found in bile, GST Pi would have little or no enzymic activity. It is proposed that GST Pi acts as a carrier protein of toxic, non-substrate, ligands to remove as yet unidentified substances from biliary epithelial cells and prevent their reabsorption.

Bile

The effect of secretin on sodium ion absorption by the isolated human gallbladder.

Sodium ion (Na+) transport, a principal function of the gallbladder epithelium, was studied by measuring the flux of 22Na across isolated human gallbladder mucosa maintained in a modified 'Ussing' flux chamber. Tissue was obtained from cholecystectomy specimens in symptomatic patients with cholelithiasis. Out of 26 gallbladders studied, 13 had a net Na+ flux from mucosa to serosa which indicated active Na+ absorption. The hormone secretin, when added to the serosal fluid, reversed the direction of net flux in these gallbladders and caused a secretion of Na+ from serosa to mucosa. These results suggest that secretin may be involved in the physiological regulation of fluid transport in the human gallbladder, and also suggest a possible role for this hormone in gallbladder emptying.

Gallbladder

Cytosolic and microsomal glutathione S-transferase isoenzymes in normal human liver and intestinal epithelium.

Glutathione S-transferases are a group of drug metabolising and detoxification enzymes. We have studied the distribution of four isoenzymes, acidic, basic, neutral, and microsomal GST in human liver, gall bladder, and small and large intestinal epithelium by immunohistochemistry. Antibodies were raised in rabbits to purified GST subunits and several formalin fixed paraffin sections of each human tissue studied using the peroxidase-antiperoxidase method. Staining density was graded from very strong (+++) to negative (-). All four enzymes were identified within the liver, the acidic GST being found almost exclusively within the biliary epithelium. The gall bladder epithelium stained strongly for acidic and basic GST. In the small intestinal epithelium the acidic and neutral GST were readily identified in villi and crypts, whilst basic GST was found only in the villi and microsomal only in the crypts. In the colonic mucosa only acidic GST could consistently be identified. This histological heterogeneity may have functional implications for these enzymes in human hepatobiliary and intestinal tissue.

Cytosol