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Biomedical subjects

I A Bouchier

Publications and source records attributed to I A Bouchier.

At least 37 records · Page 2Linked to original sources

The platelet count as a predictor of variceal hemorrhage in primary biliary cirrhosis.

BACKGROUND: Variceal bleeding is a common, life-threatening complication of primary biliary cirrhosis (PBC) that remains difficult to predict. OBJECTIVE: The aim of this study was to identify whether certain biochemical and hematological parameters may be used as predictors of variceal bleeding in patients with PBC. METHODS: Cox proportional hazard regression analysis was used to test whether various prognostic factors were significantly associated with the time of first bleeding in 63 patients with proven PBC, of whom 11 had subsequent bleeding. RESULTS: Both the first available platelet count and the bilirubin level were of significant value in predicting variceal bleeding, but only the platelet count was an independent predictor of bleeding. In the group of patients who subsequently bled, there was a progressive drop in the platelet count over the follow-up period, with a proportional increase in the risk of bleeding; a platelet count below 200 x 10(9)/L was strongly associated with variceal bleeding (p < 0.001). None of the patients with platelet count above 200 x 10(9)/L bled over a total of 136 patient-years follow-up. In the group who did not bleed, no change in platelet count was identified during follow up. CONCLUSION: We conclude that the platelet count can be used as a predictor of variceal bleeding in PBC.

Aged↗

The acute and chronic effects of isosorbide-5-mononitrate on portal haemodynamics in cirrhosis.

The effects of acute and chronic administration of isosorbide-5-mononitrate on portal and systemic circulation was studied in patients with cirrhosis and portal hypertension. Acute administration reduced the mean arterial pressure and hepatic venous pressure gradient (18.4 +/- 0.9 to 16.5 +/- 0.9 mmHg), whilst having a variable effect on azygos blood flow. The hepatic venous pressure gradient fell consistently only in patients in whom the azygos blood flow increased acutely. With chronic administration no reduction in mean arterial and hepatic venous pressure gradient was identified before rechallenge, despite a marked and consistent reduction in azygos flow (540 +/- 89 to 306 +/- 60 ml/min). Rechallenge with isosorbide-5-mononitrate in patients on chronic nitrate therapy reproduced the haemodynamic effects identified with acute administration, lowering mean arterial and hepatic venous pressure gradient (19 +/- 1.5 to 16.0 +/- 1.8 mmHg) with a variable effect on azygos flow. The wedged hepatic venous pressure was significantly lower than pretreatment values (19.9 +/- 1.6 compared with 23.4 +/- 2.1 mmHg). We conclude that acute nitrate administration lowers the hepatic venous pressure gradient, either by reducing portal venous inflow or by reducing portal-collateral resistance. Chronic administration reduces portal-collateral flow without consistently lowering the hepatic venous pressure gradient. No evidence of nitrate tolerance or tachyphylaxis was observed.

Adult↗

Hand skin temperature changes in patients with chronic liver disease.

Previous studies have shown that changes in the peripheral circulation occur in patients with liver disease. We have investigated the temperature of the hands of 26 patients and 13 controls using a liquid crystal contact thermography system. Significant differences in resting hand temperature and appearance were observed when the patients were categorised according to Child's score. The appearance depended upon the severity of liver disease; Child's A patients have warm hands of normal thermographic appearance; Child's B patients have cold hands with an abnormal thermographic appearance; whilst Child's C patients have warm hands with an abnormal thermographic appearance. After right-hand ice-cold water immersion, right-hand recovery was abnormally slow in Child's B & C groups compared with Child's A patients and controls. In addition, there was left-hand reflex vasoconstriction during the right-hand warm-up period in those with severe liver disease. With regard to autonomic function, no significant difference in right-hand temperature, thermographic appearance or warm-up rate was detected between those with and those without autonomic neuropathy. These results indicate that autonomic nervous system dysfunction is not the predominant cause of these changes.

Autonomic Nervous System↗

Effect of propranolol on prevention of first variceal bleed and survival in patients with chronic liver disease.

BACKGROUND: Propranolol has been shown to be effective in both primary and secondary treatment of variceal haemorrhage; most primary prevention trials have only included patients with large oesophageal varices. AIM OF THE STUDY: The aim of this study was to look at the effect of propranolol in the primary prevention of variceal bleeding and its long-term effects on mortality in unselected patients with chronic liver disease. METHODOLOGY: Three hundred and nineteen patients were included in a double-blind parallel group study in three centres to receive propranolol 160 mg long-acting (LA) or placebo. Patients were followed up for a minimum of one year. RESULTS: There were eleven episodes of variceal bleeding and 38 deaths with no statistically significant difference in bleeding rates between the two treatment groups. Child's group and history of ascites were the most important prognostic factors determining the likelihood of early death and variceal bleeding respectively. CONCLUSIONS: In this study we failed to demonstrate a significant effect of propranolol on first variceal bleeding or in prolonging survival in unselected patients with chronic liver disease. Our results, however, might have been influenced by the low event rate observed in these unselected group of patients and suggest that careful selection of patients who are most likely to benefit from propranolol is important.

Adult↗

Portal and systemic haemodynamic action of N-acetylcysteine in patients with stable cirrhosis.

The effects of intravenous N-acetylcysteine on hepatic and systemic haemodynamics were investigated in 11 patients with stable cirrhosis (eight alcohol; two primary biliary cirrhosis; one cryptogenic). N-acetylcysteine administration had no effect on the mean heart rate or mean arterial blood pressure despite a significant fall in systemic and pulmonary vascular resistance. Cardiac index increased but estimated liver blood flow and portal venous pressure did not change significantly. Administration of N-acetylcysteine resulted in increased oxygen delivery to the tissues because of the increased cardiac index but this was not accompanied by a rise in either arteriovenous oxygen extraction ratio or mean tissue oxygen consumption. Therefore N-acetylcysteine administration seems to confer no haemodynamic benefit to patients with cirrhosis.

Acetylcysteine↗

Autonomic function in cirrhosis assessed by cardiovascular reflex tests and 24-hour heart rate variability.

OBJECTIVES: To assess the prevalence of autonomic dysfunction in cirrhosis and to observe the effect of disease severity on autonomic dysfunction. METHODS: Seventy patients with cirrhosis (Child's class A, 42; Child's class B, 10; and Child's class C, 15) (45 alcoholic, 15 primary biliary cirrhosis, five chronic active hepatitis, and eight idiopathic) underwent standard cardiovascular reflex tests. In addition, in 40 patients, 24-h ECG RR variability tests were performed to detect autonomic dysfunction. RESULTS: Forty-two of 70 (60%) patients had abnormalities of cardiovascular reflex function of varying severity, whereas 24 of 34 (70%) had 24-h RR counts with the 95% age-related tolerance. The prevalence of abnormality increased with increasing severity of liver disease but not with different etiologies. CONCLUSION: Irrespective of etiology, there is a high prevalence of autonomic dysfunction in cirrhosis, and it is related to disease severity: the mechanism is unknown.

Autonomic Nervous System Diseases↗

Primary culture of bovine gall bladder epithelial cells.

Gall bladder epithelial cells serve numerous biological functions and abnormalities in their function are important in the pathogenesis of several gall bladder diseases. Direct studies on cell function are rare due to lack of reliable methods to culture this epithelium. This study reports a reliable and reproducible method of harvesting and culturing gall bladder epithelial cells. Normal bovine gall bladder epithelium, obtained within 20 minutes of slaughter, was rinsed with modified Hanks's balanced salt solution, the mucosa separated and incubated in trypsin--EDTA solution at 37 degrees C. The cells were isolated and resuspended in Dulbeco's modification of Eagles' medium containing 10% fetal calf serum and, after filtration and centrifugation, were plated under aseptic conditions. The growth rate was established by flow cytometry and the morphological characteristics of the growing cells by electron microscopy. Gall bladder epithelial cells grew successfully and visible clusters of cells were present by day two, confluency being reached at 8 to 10 days in collagen coated plates and 12 to 14 days in uncoated plates. Electron microscopy showed typical gall bladder epithelia with microvilli, tight junctions, and mucus droplets. This method proved reliable and reproducible for the culture of gall bladder epithelial cells and should allow direct studies of the biological properties of these cells in human tissue.

Animals↗

Transjugular intrahepatic portasystemic stent shunting for control of acute and recurrent upper gastrointestinal haemorrhage related to portal hypertension.

The insertion of a transjugular intrahepatic portasystemic stent shunt (TIPSS) was evaluated in 22 patients with recurrent upper gastrointestinal haemorrhage related to portal hypertension (bleeding from oesophageal varices 10, gastric varices six, portal hypertensive gastropathy six). TIPSS was successfully performed electively in 15 patients and as an emergency in three patients. Twelve patients have had no further admissions with bleeding after TIPSS. Single episodes of bleeding were noted in six patients after TIPSS associated with shunt thrombosis (two), intimal hyperplasia within the shunt (two), and shunt migration (one). Another patient presented with reaccumulated ascites suggesting poor shunt function but died from massive variceal haemorrhage before further assessment could be performed. There was one death related to the procedure. Two patients developed encephalopathy after TIPSS, in one patient this was controlled by the insertion of a smaller diameter stent within the existing TIPSS. Several complications arose in earlier patients that have not recurred after modification of the initial technique. TIPSS can be life saving and is effective in controlling variceal haemorrhage and rebleeding from oesophageal or gastric varices and portal hypertensive gastropathy. Larger and longer term studies are required, however, to define the role of TIPSS in the overall management of such patients.

Acute Disease↗

A patient with neurosyphilis presenting as chorea.

Despite the marked decline in frequency of neurosyphilis over the past three decades in the United Kingdom, new cases continue to appear both sporadically and as a complication of HIV infection. There is clinical evidence that neurosyphilis is becoming less typical. We describe a case of neurosyphilis presenting predominantly with choreoathetosis and associated hemiparesis in an otherwise healthy, immunocompetent patient. Only six cases of neurosyphilis presenting with features of basal ganglia damage have been reported in the recent literature, five of whom had HIV infection.

Athetosis↗

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↗