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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
PubMed1998

Natriuretic effect of an adenosine-1 receptor antagonist in cirrhotic patients with ascites.

BACKGROUND & AIMS: The sodium and water retention and renal vasoconstriction exhibited by patients with cirrhotic ascites are similar to the changes observed by stimulation of renal adenosine 1 receptors. The aim of this study was to investigate the effects of FK352 (an adenosine 1 antagonist) on renal and systemic hemodynamics and renal function in cirrhotic patients with ascites. METHODS: p-Aminohippuric acid and inulin clearance, urine flow rate, sodium and potassium excretion, and free water clearance were measured for 2 hours before and after FK352 administration. Cardiac output, systemic vascular resistance, plasma angiotensin II level, plasma renin activity, and noradrenaline, adrenaline, and adenosine 3', 5'-cyclic monophosphate (cAMP) levels were also measured before and after FK352. RESULTS: Urine sodium excretion and urine flow rate increased after FK352 by a mean of 199.9% +/- 43.0% (P < 0.001) and 51.2% +/- 17.5% (P < 0.02), respectively. Plasma cAMP and angiotensin II levels and plasma renin activity also increased by 10. 8% +/- 3.2% (P < 0.01), 36.9% +/- 11.3% (P < 0.01), and 247.9% +/- 82.6% (P < 0.02), respectively. No change was detected in any other parameter. CONCLUSIONS: The isokaliuretic improvement in natriuresis and diuresis suggests a role for adenosine 1 antagonism in the treatment of the renal abnormalities found in advanced cirrhosis.

Ascites↗
PubMed1998

Direct measurement of post-prandial portal haemodynamics in cirrhotic patients with a transjugular intrahepatic portosystemic stent-shunt.

OBJECTIVE: Portal haemodynamics vary in response to eating and other stimuli, but any increase in portal venous pressure (PVP) in cirrhotic patients may be a risk factor for variceal bleeding. We directly assessed post-prandial splanchnic haemodynamics in cirrhotic patients with a transjugular intrahepatic portosystemic stent-shunt (TIPSS) in situ. METHODS: A thermodilution catheter was inserted via the patent TIPSS into the portal vein in 12 cirrhotic patients. PVP,portal venous flow (PVF) (thermodilution method), portal vascular resistance (PVR), porto-atrial pressure gradient (PPG), heart rate, mean arterial pressure (MAP) and right atrial pressure (RAP) were measured. A 505 kcal meal was given and all haemodynamic measurements were repeated at 15 min intervals for 60 min. RESULTS: Following the meal, there was a significant rise in PVP from 11.2 +/- 1.5 to 14.0 +/- 1.9 mmHg at 15 min, and 14.0 +/- 1.8 mmHg at 30 min (P < 0.001); in PPG from 9.5 +/- 1.4 to 12.7 +/- 2.2 mmHg at 15 min and 12.7 +/- 2.1 mmHg at 30 min (P < 0.005); and in PVF from 1110.2 +/- 141.1 to 1543.2 +/- 227.6 ml/min at 30 min (P < 0.01). PVR feil from 0.08 +/- 0.01 to 0.05 +/- 0.01 RU at 30 min (P < 0.05). Heart rate increased from 77 +/- 4.1 to 80.5 +/- 5.4 bpm at 15 min (p < 0.05), but MAP and RAP remained unchanged. CONCLUSION: In cirrhotic patients with TIPSS, significant changes in portal haemodynamics occur at 15-30 min following a meal, with minimal effect on systemic haemodynamics. This model offers a new technique to directly assess the causes for and possible treatments of post-prandial splanchnic hyperaemia in cirrhosis.

Blood Pressure↗
PubMed1998

Acute effects of transjugular intrahepatic portosystemic stent-shunt (TIPSS) procedure on renal blood flow and cardiopulmonary hemodynamics in cirrhosis.

OBJECTIVE: An acute increase in portal pressure is associated with an immediate reduction in renal blood flow. It has been suggested that this supports the presence of an hepatorenal reflex. In this study, we used TIPSS placement as a model to investigate the effect of an acute reduction in portal pressure on renal blood flow and cardiopulmonary hemodynamic parameters. METHODS: Eleven cirrhotic patients were studied during elective TIPSS placement for variceal hemorrhage (n = 9) or refractory ascites (n = 2). Unilateral renal blood flow (RBF) was measured before and at 5, 15, 30, 45, and 60 min after shunt insertion. Heart rate (HR), mean arterial pressure (MAP), right atrial pressure (RAP), mean pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), cardiac output (CO), and systemic vascular resistance (SVR) were also measured before and 30 min after TIPSS placement. RESULTS: Despite significant increases in CO (p = 0.001), RAP (p < 0.001), PAP (p < 0.001), and PCWP (p = 0.001), and a fall in SVR (p = 0.003), no change was observed in RBF, HR, or MAP after TIPSS placement. The fall in the portoatrial pressure gradient correlated only with the rise in CO (p < 0.05) and the drop in SVR (p < 0.05). CONCLUSION: Despite the fall in portal pressure and the systemic hemodynamic changes caused by TIPSS placement, there is no immediate effect on RBF. Any improvement in renal function after TIPSS procedure does not appear to be due to an acute increase in RBF.

Blood Pressure↗
PubMed1998

Acute effect of propranolol and isosorbide-5-mononitrate administration on renal blood flow in cirrhotic patients.

BACKGROUND: Propranolol and isosorbide-5-mononitrate (ISMN) are increasingly used in the prophylaxis of variceal haemorrhage in cirrhosis. However, recent studies have suggested that these drugs may compromise renal function, possibly by reducing renal blood flow. AIMS: To assess the acute effects of propranolol and ISMN on renal blood flow and other haemodynamic parameters in cirrhosis. PATIENTS AND METHODS: Twenty six cirrhotic patients were given either 80 mg propranolol, 20 mg ISMN, or a combination of the two drugs. Unilateral renal blood flow (RBF), azygos blood flow (AZBF), hepatic venous pressure gradient (HVPG), mean arterial pressure (MAP), and heart rate (HR) were recorded prior to and one hour after drug administration. RESULTS: Propranolol caused a reduction in HR (p < 0.005), AZBF (p < 0.01), and HVPG (p = 0.05), but no change in MAP or RBF (454.1 (77.3) versus 413.9 (60.3) ml/min). ISMN reduced MAP (p < 0.005) and HVPG (p < 0.01), but had no effect on HR, AZBF, or RBF (302.5 (49.4) versus 301.7 (58.8) ml/min). Combined treatment reduced MAP (p < 0.005), AZBF (p < 0.05), and HVPG (p = 0.002), but HR and RBF (419.2 (62.6) versus 415.1 (61.1) ml/min) remained unchanged. CONCLUSIONS: Despite the anticipated changes in other haemodynamic parameters, acute propranolol and/or ISMN administration did not reduce RBF. These drugs do not seem to compromise RBF in cirrhosis.

Adult↗
PubMed1997

Peripheral eosinophil count both before and after liver transplantation predicts acute cellular rejection.

Acute cellular rejection is common after orthotopic liver transplantation and an important cause of graft dysfunction. Eosinophils, potent mediators of tissue damage, have been implicated in the pathogenesis of acute rejection. We studied 55 patients, all of whom had a protocol biopsy 7 days after transplantation and whose peripheral eosinophil count was monitored daily for 11 days after transplantation. Patients were divided clinicopathologically into two groups: group A, without rejection, group B, with rejection. Group B (36% of patients) developed rejection within the 11-day study period. The pretransplant eosinophil count was significantly higher in group B, compared with group A (0.31 +/- 0.08 v 0.10 +/- 0.01 (x10(9)/L), p < .001). After transplantation, the eosinophil count fell to low levels in both groups. By day 3 there was a statistically significant rise in the eosinophil count in group B compared with group A, with a maximum at day 7 [0.51 +/- 0.06 v 0.26 +/- 0.03 (x10(9)/L) p < .001]. After treatment with steroids, the eosinophil count dropped to values similar to those in group A and remained low thereafter in 16 of 20 patients. Four patients had a second episode of rejection; in each of these, eosinophils were raised again and decreased with resolution of the rejection. An eosinophil count threshold of 0.13 (x10(9)/L) before transplantation and 0.33 (x10(9)/L) on day 7 after transplantation predicted the development of rejection (sensitivity 72/70%, specificity 66/63%, negative predictive value 82/79%). We conclude that a raised eosinophil count is associated with acute rejection. The raised eosinophil count before transplantation in group B suggests that these patients are predisposed to acute rejection, and earlier intervention may be indicated.

Adult↗
PubMed1997

The correction of autonomic dysfunction in cirrhosis by captopril.

BACKGROUND/AIMS: Vagal dysfunction is reported in about 70% of patients with cirrhosis, irrespective of aetiology, as detected by cardiovascular reflex tests. We have previously shown that RR-variability on 24-h ECG is a more sensitive marker of vagal dysfunction in cirrhosis. Angiotensin II inhibits vagal function in animals, and it is elevated in cirrhosis and may be the cause of the vagal dysfunction. Our aim was to observe the effect of captopril on vagal dysfunction in cirrhosis. METHODS: Eight patients with cirrhosis (biopsy proven, male two, female six, mean age 54.25) had 24-h ECG RR-variability performed. They then received captopril 25 mg t.d.s. for 48 h. The 24-h ECG was repeated on therapy. RESULTS: Mean blood pressure remained unchanged: baseline 89.8 +/- 4.8 mmHg (mean +/- sem) versus 91.8 +/- 5.9 mmHg, p = not significant. Median baseline RR-variability was 791 (range 18-5344) counts/24 h and increased in all but one patient, with captopril, to 1548 (56-4824) p = 0.008. Three increased into the normal range. CONCLUSION: The vagal dysfunction of cirrhosis is caused by neuromodulation by angiotensin II and is not due to a neuropathy.

Adult↗
PubMed1997

A comparison between gastric and oesophageal variceal haemorrhage treated with transjugular intrahepatic portosystemic stent shunt (TIPSS).

BACKGROUND: Transjugular intrahepatic portosystemic stent-shunts (TIPSS) are becoming widely used in the management of oesophageal variceal haemorrhage (OVH). Their place in the treatment of gastric variceal haemorrhage (GVH), a condition with a traditionally poor prognosis, remains unclear. The aims of our study were to compare portal haemodynamics and patient outcome in patients undergoing TIPSS for either GVH or OVH. PATIENTS AND METHODS: 106 consecutive patients undergoing TIPSS at our institution for either GVH (32 patients) or OVH (74 patients) were studied. The groups were similar with regard to patient age, aetiology and severity of liver disease and number of procedures carried out as an emergency (34.4% vs. 36.5%). Episodes of shunt insufficiency, rebleeding, encephalopathy and other clinical sequela were recorded. Mean follow-up was similar in both patient groups (14.2 vs. 12.1 months). RESULTS: Baseline portocaval pressure gradient was lower in patients with GVH compared with those with OVH (13.0+/-0.9 mmHg vs. 19.0+/-0.6 mmHg) (P < 0.001). Rates of variceal rebleeding, encephalopathy and shunt insufficiency during follow-up were similar in both groups and there was no difference in survival. CONCLUSION: Patients with GVH had markedly lower portocaval pressure gradients than those with OVH, but shunt and clinical complications and survival were similar during follow-up. TIPSS appears to be an effective treatment for GVH and should be compared with endoscopic or surgical techniques in controlled trials.

Esophageal and Gastric Varices↗
PubMed1997

Acute effect of low dose theophylline on the circulatory disturbances of cirrhosis.

BACKGROUND: Adenosine is a potent vasoactive substance that may be responsible for mediating the altered haemodynamics found in patients with cirrhosis. AIM: The administration of oral theophylline was used to investigate the effect of adenosine receptor antagonism upon the circulation of patients with cirrhosis. METHODS: Twenty eight patients were given oral theophylline and intravascular haemodynamic measurements obtained over approximately one hour. RESULTS: After 240 mg of oral theophylline elixir the hepatic venous pressure gradient mean fell from 21.8 (2.1) to 19.9 (2.4) mm Hg (p < 0.01), and azygos blood flow fell from 481 (94) to 375 (83) ml/min (p < 0.05). There were no changes in cardiac output or systemic vascular resistance despite a fall in mean arterial pressure (92.2 (2.0) to 89.2 (1.8) mm Hg; p < 0.05) and a rise in heart rate (78.3 (3.0) to 82.4 (3.2); p < 0.001). Left renal vein flow measured by a reverse thermodilution catheter rose from 387 (91) to 601 (119) ml/ min (p < 0.05). The proportion of cardiac output perfusing the left kidney rose from 5.0 (1.3) to 9.7 (2.8)%. CONCLUSIONS: These changes indicate a significant role for adenosine in the renal vasoconstriction and a more minor role in the maintenance of portal hypertension.

Adenosine↗
PubMed1996

Acute haemodynamic changes after oral carvedilol, a vasodilating beta-blocker, in patients with cirrhosis.

BACKGROUND/AIMS: Combinations of beta-blockers and vasodilators have been assessed for their ability to lower portal pressure and so prevent variceal haemorrhage. However, reservations have been raised particularly with respect to renal function and perfusion after the use of these medicines in patients with chronic liver disease. We studied the acute effects of carvedilol, a new vasodilating beta-blocker which combines non-selective beta-blockade with alpha-1 receptor antagonism, upon the haemodynamics of patients with cirrhosis. METHODS: Sixteen patients completed the study which measured the changes approximately 1 h after the administration of 25 mg oral carvedilol. RESULTS: The hepatic venous pressure gradient fell from 16.7 +/- 0.9 to 13.6 +/- 1.0 mmHg (p < 0.00001), accounted for largely by reductions in the wedged hepatic venous pressure. Despite this, the azygos blood flow did not change. There was a significant fall in mean arterial pressure (94.8 +/- 4.4 cf. 84.6 +/- 4.3 mmHg; p = 0.0001), which was particularly apparent in the diastolic blood pressure of those patients with ascites. The heart rate only fell significantly in the ascitic subjects. No significant changes occurred in the cardiac output or systemic vascular resistance. Unilateral renal vein flow as measured by the reverse thermodilution technique remained constant. CONCLUSIONS: Carvedilol is therefore a potent acute portal hypotensive agent which does not appear to compromise renal perfusion. However, patients with ascites are at greater risk of its systemic hypotensive action.

Administration, Oral↗
PubMed1996

Neutrophil activation in chronic liver disease.

OBJECTIVE: To assess the relationship between neutrophil activation and indices of disease severity in patients with chronic liver disease. METHODS: Plasma neutrophil elastase was measured by radioimmunoassay as a marker of neutrophil activation, and disease severity assessed by standard clinical, biochemical, haematological and histological techniques. PATIENTS: Eighty-eight patients with chronic liver disease were studied, Thirty-nine had alcohol-induced liver disease (ALD), 18 autoimmune chronic hepatitis, 13 cryptogenic cirrhosis, seven primary biliary cirrhosis, six primary sclerosing cholangitis, three haemochromatosis and two secondary biliary cirrhosis. Seventy-three patients were cirrhotic and 15 were non-cirrhotic, confirmed by biopsy. RESULTS: Levels of neutrophil elastase were raised in Childs C cirrhotic patients with ALD compared with Childs A or B patients with ALD (P < 0.01), Childs A or B patients with non-ALD (P < 0.01), and Childs C patients with non-ALD (P = 0.02). In patients with ALD, neutrophil elastase correlated with prothrombin time (r = 0.679, P = 0.001), bilirubin (r = 0.587, P < 0.001), Child-Pugh score (r = 0.546, P < 0.001) and inversely with serum albumin (r = -0.511, P < 0.001). In patients with non-ALD, there were no correlations with the measurements of with transaminase levels. CONCLUSION: Neutrophil activation, as measured by plasma neutrophil elastase, is a marker of disease severity in patients with alcohol-induced chronic liver damage, but not in those with other causes of liver disease.

Autoimmune Diseases↗
PubMed1995

Exercise-induced left ventricular dysfunction in alcoholic and non-alcoholic cirrhosis.

BACKGROUND/AIMS: Autonomic and cardiac dysfunction have been reported in patients with cirrhosis. We studied left ventricular and autonomic function in 20 patients with both alcoholic and non-alcoholic cirrhosis. METHODS: Autonomic function was assessed by a standard battery of cardiovascular reflex tests. Supine exercise radionuclide ventriculography was used to assess the cardiac response to exercise. RESULTS: Exercise capacity was reduced in all patients in association with marked chronotropic incompetence (peak heart rates 120.5 +/- 6 bpm). Unlike normal subjects there was no increase in left ventricular ejection fraction on exercise. Stroke volume increased by 23 +/- 6%, mediated by an increase in end-diastolic.volume of > 20%. Cardiac output was subnormal at maximal exercise, increasing by only 96 +/- 14% and 97 +/- 11% in alcoholic and non-alcoholic groups respectively. The majority (83%) of our patients had autonomic reflex abnormalities. CONCLUSIONS: Patients with cirrhosis of alcohol and non-alcohol related aetiologies have significantly impaired cardiovascular responses to exercise, which are similar to those of a denervated heart. This may have important clinical implications for the ability of these patients to withstand cardiovascular stress.

Autonomic Nervous System↗
PubMed1995

Middle cerebral artery blood flow velocity in patients with cirrhosis.

BACKGROUND: Brain dysfunction is common in patients with advanced liver disease; it is often manifested as hepatic encephalopathy, but its cause is not clearly understood. METHODOLOGY: Intracranial blood flow velocity parameters, including peak systolic velocity, end diastolic velocity and mean velocity of both middle cerebral arteries were measured by transcranial Doppler ultrasonography in 37 patients with cirrhosis without encephalopathy (16 Child's A, 10 Child's B and 11 Child's C) and 12 normal controls. The cause was alcohol-related in 24 and non-alcohol-related in 13. RESULTS: No significant differences in any of the Doppler parameters were detected in Child's group A when compared with controls. However, a statistically significant decrease in middle cerebral artery blood flow velocity was evident when Child's B and C patients without clinically apparent encephalopathy were compared with controls irrespective of the cause. Our results demonstrate that intracranial blood flow is abnormal in patients with advanced liver disease without clinically apparent encephalopathy.

Analysis of Variance↗
PubMed1995

Liver biopsy findings in patients with alcoholic liver disease complicated by chronic hepatitis C virus infection.

OBJECTIVE: To identify the features of concurrent hepatitis C virus (HCV) infection in liver biopsies from patients thought to have alcoholic liver disease. PATIENTS: Fifty-five patients with a history of excess alcohol consumption were studied. METHODS: All patients underwent liver biopsy. RESULTS: Eight of the 55 patients studied were found to be HCV-positive. CONCLUSION: The histological features found to be most useful for identifying concurrent HCV infection were the presence of lymphoid aggregates in portal tracts (predictive value 100%), the presence of lymphocytes in the lobules (predictive value 83%), and the pattern of fibrosis, particularly periportal spurring rather than perivenular fibrosis (predictive value 75%).

Adult↗
PubMed1995

The effect of alcohol on acid secretion by the bovine gall bladder in vitro.

OBJECTIVES: To determine whether acid secretion by gall bladder mucosa is influenced by alcohol and whether hydrogen ion output is increased when the gall bladder is perfused with moderate concentrations of alcohol. METHODS: Fifty bovine gall bladders were studied. Twenty-five served as controls and 25 were perfused (in groups of five) with varying concentrations of alcohol (w/v): 0.05, 0.1, 0.2, 0.5 and 1.0%. Acid output was measured over 1 h and the results expressed as the mean. RESULTS: There was no significant difference between acid production by control gall bladders and those perfused with 0.05% alcohol (24.30 +/- 8.7 versus 18.95 x 8.41 nmol/h), but the acid output was significantly increased when the mucosa was exposed to 0.1 and 0.2% alcohol concentrations (50.28 +/- 10.2 and 29.34 +/- 9.1 nmol/h; P < 0.001 and P < 0.0004, respectively). Perfusion with alcohol concentrations of 0.5 and 1.0%, significantly inhibited mucosal acid output (2.60 +/- 2.0 and -1.70 +/- 1.2 nmol/h; P < 0.0001 and P < 0.0001, respectively). CONCLUSION: This study shows that perfusion of bovine gall bladder mucosa in vitro with moderate concentrations of alcohol stimulates acid output. This observation is important for assessing the link between alcohol and the risk of gallstone formation.

Acids↗