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Biomedical subjects

D R Triger

Publications and source records attributed to D R Triger.

At least 19 recordsLinked to original sources
PubMed1992

Natural history of autonomic neuropathy in chronic liver disease.

To determine the natural history of autonomic neuropathy in chronic liver disease we used standard cardiovascular autonomic tests to evaluate prospectively 60 patients (33 male, 27 female) with initially well-preserved hepatic function. On initial testing, 27 patients (45%; median [range] age 56 [32-67] years) had vagal neuropathy. Autonomic dysfunction was equally common in patients with alcohol-related and nonalcoholic-related liver disease. The cumulative 4-year mortality rate in patients with vagal neuropathy was 30% compared with 6% in those with normal autonomic function. Multiple logistic regression analysis showed that presence of vagal neuropathy and severity of hepatic damage were independent predictors of mortality. Serial testing showed that whereas disease progression occurred in some patients, in others mild abnormalities in autonomic function were reversible. Vagal dysfunction is common in well-compensated chronic liver disease and its presence identifies a subgroup of patients with a substantially worse outlook.

Adult↗
PubMed1992

Selenium in chronic liver disease.

In order to assess the role of selenium (Se) in chronic liver disease, we have measured serum, urinary and hepatic selenium in a range of liver diseases and correlated them with nutritional status and conventional liver biochemistry. Serum Se levels (microgram/l +/- S.D.) were significantly lower in both alcoholic (63.6 +/- 18.2, p less than 0.0001) and non-alcoholic liver disease (NALD) (60.6 +/- 13.6, p less than 0.0001) compared to healthy controls (87.8 +/- 21.2) and non-malignant 'disease controls' (80.3 +/- 19.1). Hepatic Se levels (microgram/g of dry weight) were also reduced in both ALD (0.568 +/- 0.647, p less than 0.005) and NALD (0.863 +/- 0.308, p less than 0.005) compared to controls (1.227 +/- 0.296), 24-h urinary Se excretion (microgram) in ALD (24.6 +/- 10.7) and NALD (29.0 +/- 14.3) was similar to controls (30.3 +/- 8.7). Serum Se showed a highly significant positive correlation with albumin (p less than 0.001) in both ALD and NALD. Serum levels were also significantly correlated with anthropometric measurements. Dietary assessment of patients with primary biliary cirrhosis and low serum Se levels did not show a reduced dietary intake. Our data show that Se levels are low in liver disease irrespective of aetiology and suggest that these low levels are more likely to be related to overall nutritional status than to dietary intake.

Adult↗
PubMed1992

Portal hypertensive gastropathy.

There is now substantial clinical evidence to suggest that portal hypertensive gastropathy is an important source of gastrointestinal bleeding in patients with portal hypertension. Although a relatively uncommon presenting feature in such patients, it appears to become progressively more frequent and important the longer such patients with bleeding oesophageal varices survive after treatment by endoscopic sclerotherapy. It is now being increasingly recognized as the most important cause of haemorrhage after oesophageal varices in such patients. The endoscopic and histological characteristics of the condition are now well established but from a clinical point of view it is important to distinguish it from a number of other disorders. The pathogenesis of portal hypertensive gastropathy is poorly understood; venous congestion secondary to portal hypertension undoubtedly plays an important role but this is not thought to account entirely for the condition since abnormalities in the arterial blood supply are also observed. Many abnormalities in gastric mucosal function have been reported but it is unclear whether these are secondary disturbances or whether they play an important primary role in the development of the condition. Animal studies to date have not been helpful due to the lack of a satisfactory experimental model. Portocaval shunt surgery cures portal hypertensive gastropathy but propranolol has been shown to be highly effective in controlling haemorrhage from this condition and should now be considered the treatment of choice. The mechanism of action is unclear, and it remains to be shown whether other beta-blockers, or indeed any other drugs, are useful in treating this disorder.

Animals↗
PubMed1992

Peripheral and cardiovascular autonomic impairment in chronic liver disease: prevalence and relation to hepatic function.

We have evaluated autonomic function using standard cardiovascular tests and a test of peripheral autonomic denervation, the acetylcholine sweatspot test, in 104 patients with biopsy proven chronic liver disease and 35 age- and sex-matched controls. Cardiovascular autonomic dysfunction was significantly more frequent in advanced liver disease compared with early liver disease (71.8% Child B or C vs. 39.7% Child A; p < 0.0006), and a strong correlation between the number of abnormal tests and Child-Pugh score could be demonstrated (Rs = 0.5; p < 0.0001). On multiple logistic regression analysis, cardiovascular autonomic dysfunction was related to age and to Child-Pugh score and occurred independently of the aetiology of liver disease. Peripheral autonomic denervation was found in 39% of patients, was significantly associated with cardiovascular abnormalities (p < 0.009) and correlated with the number of abnormal cardiovascular tests in each patient (Rs = 0.48; p < 0.0001). In chronic liver disease, the prevalence and severity of cardiovascular autonomic dysfunction is related to the severity of hepatic dysfunction and is independent of aetiology, suggesting a common pathogenetic basis related to hepatic damage; the association with peripheral autonomic denervation indicates that at least some of the abnormalities may be due to a true autonomic neuropathy. The possible significance of these findings to the complications of cirrhosis is discussed.

Acetylcholine↗
PubMed1992

A study of the penetration of meropenem into bile using endoscopic retrograde cholangiography.

One gram of meropenem was administered as prophylaxis to patients undergoing endoscopic retrograde cholangiography (ERC) in a study of the bile pharmacokinetics of this agent. Twenty-four patients were evaluated and a single bile sample was collected from each one during ERC at different time intervals following intravenous infusion. Bile concentrations after the dose ranged from 0.7 to 25.7 mg/L (mean 11.1) and exceeded the MIC90s for the pathogens most commonly associated with biliary tract infections for up to 203 mins. The bile concentrations of 13 patients with biliary tree obstruction were compared with those of 11 patients without obstruction. Bile concentrations in excess of the MIC90s for the predominant pathogens were achieved in both groups; a positive correlation between meropenem bile concentration and the time of dose administration was demonstrable only for the obstructed group. ERC may be a useful technique for biliary pharmacokinetic studies.

Adult↗
PubMed1992

A prospective trial of endoscopic sclerotherapy v oesophageal transection and gastric devascularisation in the long term management of bleeding oesophageal varices.

In a prospective three centre study oesophageal transection and gastric devascularisation have been compared with endoscopic sclerotherapy in the long term management of bleeding oesophageal varices. Cirrhotic patients (Child's A or B grade) with documented bleeding oesophageal varices were treated initially with emergency sclerotherapy, and after five days stability, were allocated to one of the two treatment regimes. The endoscopic sclerotherapy group underwent regular sclerotherapy until variceal obliteration while those undergoing surgery were not endoscoped unless bleeding recurred, when they were treated by sclerotherapy if appropriate. Ninety two patients were eligible for analysis (68% alcoholic cirrhosis; mean age 50.1 years) and follow up was achieved for a mean of 52.5 months (range 17-83). Mortality in the first three months was greater in the oesophageal transection and gastric devascularisation group (20% v 1%) but by two years the survival curves were the same and thereafter there was no difference in mortality. Rebleeding occurred in 13/41 (31%) patients, undergoing oesophageal transection and gastric devascularisation. The costs incurred during the first year of oesophageal transection and gastric devascularisation treatment were significantly greater than with endoscopic sclerotherapy (4369 pounds v 1067 pounds, p < 0.0001) and the high rate of rebleeding in the surgical group meant that no cost savings occurred in subsequent years. It is concluded that oesophageal transection and gastric devascularisation confers no benefit over endoscopic sclerotherapy in terms of long term survival and that it is not cost effective as judged by the current health care costs in the United Kingdom.

Adult↗
PubMed1992

Liver blood flow: non-invasive estimation using a gamma camera.

A non-invasive radioisotope technique for the measurement of total liver blood flow (TBF) is described. The method requires the use of two intravenously administered tracers, 99mTc (technetium 99m) human serum albumin (HSA) and 99mTc colloid. Computer analysis of first-pass time activity curves for HSA for liver and lung tissues yields values for the arterial and portal contributions to liver blood flow, from which TBF can be determined. These values are then corrected for attenuation using the images of the colloid distribution. The use of the method is illustrated in 17 subjects. Assumptions, limitations and possible applications of the technique are discussed.

Colloids↗
PubMed1991

A randomized controlled trial of recombinant interferon-alpha in chronic hepatitis C in hemophiliacs.

Chronic liver disease associated with hepatitis C virus (HCV) is an important cause of morbidity and mortality in hemophilia. We have used recombinant interferon alpha-2b (IFN alpha-2b) in a randomized controlled liver biopsy trial to treat hemophiliacs with chronic hepatitis. Eighteen patients entered the study, 16 of whom were subsequently shown to have antibodies to the HCV. All underwent liver biopsy at entry and were randomized to either treatment with self-administered IFN alpha-2b, 3 million units subcutaneously thrice weekly (n = 10) or no treatment (control group) (n = 8). Nine subjects had chronic active hepatitis, seven had chronic persistent hepatitis, and two had cirrhosis. Twelve months after entry into the study 17 patients underwent a second liver biopsy. All biopsies were coded, assessed, and scored according to the histologic severity of the liver disease. Ten patients were administered IFN for 1 year, and in four patients normalization of alanine aminotransferase (ALT) occurred compared with none in the untreated group. After the second liver biopsy, six of the eight initial no-treatment patients were treated with interferon 3 million units thrice weekly for 6 months, and normalization of ALT was seen in five patients. Biochemical relapse within 4 months of stopping IFN occurred in one of four patients treated for 1 year and in four of five patients treated for 6 months. IFN treatment was well tolerated. Although the histologic scores of the two groups were similar at entry into the study, after 12 months the biopsy appearances in the treated group were significantly improved compared with the controls (P less than .01). Histologic improvement was noted in the three interferon-treated human immunodeficiency virus antibody-positive patients and also in other patients who had no biochemical response. We conclude that low-dose recombinant IFN alpha is effective in normalizing transaminases and improving the histologic appearances in at least 50% of hemophiliacs with chronic hepatitis C.

Adult↗
PubMed1991

Indocyanine green elimination in patients with liver disease and in normal subjects.

1. The validity of a two-compartment pharmacokinetic model for the estimation of the hepatic extraction ratio of Indocyanine Green was tested in six patients with cirrhosis of the liver. 2. No agreement was found between the value of the hepatic extraction ratio measured directly and that calculated using the two-compartment model. 3. To investigate the reasons for the failure of the model, an extended sampling period was used to define the time course of Indocyanine Green in plasma in six healthy subjects and in six patients with cirrhosis of the liver after a bolus injection of the dye. 4. Indocyanine Green was measurable in the plasma for up to 10 h after injection in healthy subjects, and up to 48 h after injection in the patients. The plasma elimination curve in both groups was best described by a triexponential function. 5. The clearance of Indocyanine Green calculated using data collected in the first 20 min after injection overestimated that calculated using data collected for as long as Indocyanine Green was measurable in the plasma. In the patients with cirrhosis the mean overestimate was 87%. 6. Thus, a two-compartment pharmacokinetic model was inappropriate for the description of the disposition of Indocyanine Green and estimates of the hepatic extraction ratio obtained using this model in patients with cirrhosis were inaccurate.

Female↗
PubMed1991

Clinical features, pathophysiology and relevance of portal hypertensive gastropathy.

The frequency and importance of gastric mucosal lesions in patients with portal hypertension have been increasingly recognized in recent years. This article describes the clinical and endoscopic features of portal hypertensive gastropathy and reviews the current state of knowledge concerning the pathophysiology and treatment of the disorder.

Gastric Mucosa↗
PubMed1991

Inter-relationships between platelet count, platelet IgG, serum IgG, immune complexes and severity of liver disease.

Thrombocytopenia is a common finding in subjects with chronic liver diseases. A variety of mechanisms may underlie this. Immunological disturbances are commonly a feature in chronic liver disease, including hyperglobulinaemia and the presence of autoantibodies and circulating immune complexes and immune mechanisms could therefore contribute to thrombocytopenia. We have investigated the relationships between blood platelet count, serum IgG and IgG immune complexes and IgG associated with platelets in 92 subjects with chronic liver disease (27 with chronic active hepatitis, 38 with primary biliary cirrhosis and 27 with alcoholic liver disease). Severity of liver impairment was a major determinant of degree of thrombocytopenia. Also, an inverse relationship was demonstrated between platelet count and platelet-associated IgG. In subjects with chronic active hepatitis the relationships between platelet count, serum IgG immune complexes and platelet-associated IgG were consistent with a role for immune mechanisms in general and immune complexes in particular as mediators of the thrombocytopenia.

Antigen-Antibody Complex↗
PubMed1991

Prophylactic sclerotherapy for esophageal varices: long-term results of a single-center trial.

Survival after prophylactic sclerotherapy was assessed in a single-center study involving 99 cirrhotic (41 alcoholic) patients enrolled over 8-yr. The wedged hepatic vein pressure gradient was measured; those with pressure greater than or equal to 12 mm Hg were randomized to receive sclerotherapy or no treatment. The rest were not randomized. Patients in all three groups who bled were treated with emergency endoscopy and sclerotherapy. Stratification according to presence of ascites was also undertaken. Median follow-up was 61 mo (range = 14 to 107 mo). Survival among unrandomized patients was significantly longer than among randomized patients (p less than 0.006), but there was no significant difference between those treated by sclerotherapy and the controls (p = 0.27). Alcoholic cirrhotic patients undergoing sclerotherapy had better 2-yr survival than did the controls (80% vs. 43%; p = 0.09), but this benefit was not sustained at 5 yr. Survival in the nonalcoholic patient groups was identical. Only 10 of 50 deaths were caused by variceal bleeding. Forty-eight percent of patients with large varices bled, compared with 20% of patients with small varices. Wedged hepatic vein pressure less than 12 mm Hg accurately identified alcoholic patients at low risk of variceal bleeding but not nonalcoholic patients. Only four episodes of variceal bleeding were attributable to elective sclerotherapy. We conclude that in our population, prophylactic sclerotherapy alone does not improve survival. The discrepancy in survival between alcoholic and nonalcoholic cirrhotic patients suggests that factors other than variceal hemorrhage may be responsible for the difference.

Adolescent↗
PubMed1990

Hepatitis C antibody and chronic liver disease in haemophilia.

A radioimmunoassay was used to detect antibodies to hepatitis C virus (anti-HCV) in 154 patients with haemophilia. Prevalence of anti-HCV was associated with exposure to clotting factor concentrates. 76 of 129 (59%) who had received factor VIII or IX had anti-HCV: 42 of 55 (76%) who required over 10,000 units of concentrate annually had anti-HCV, compared with 34 of 74 (46%) who required less, and 0 of 25 patients who had never received concentrates. Anti-HCV were significantly more common in patients seropositive for antibodies against human immunodeficiency virus (anti-HIV) or with markers of previous hepatitis B infection than in those without anti-HIV or hepatitis B markers (88% vs 39% and 75% vs 46%, respectively). 5 of 23 (22%) haemophiliacs treated only with heated concentrates had anti-HCV compared with 71 of 106 (67%) patients who received unmodified products. 35 patients with chronic liver disease underwent liver biopsy: histological examination showed features associated with post-transfusion hepatitis in 24, all of whom were anti-HCV-positive; of the other 11 patients with no histological features of non-A, non-B hepatitis, 5 were anti-HCV-positive. HCV appears to be the major predisposing factor for most non-A, non-B hepatitis and chronic liver disease in haemophilia.

Adolescent↗
PubMed1990

A randomised prospective trial comparing daily paracentesis and intravenous albumin with recirculation in diuretic refractory ascites.

We report a randomised trial in 40 consecutive patients with diuretic refractory ascites comparing our standard therapy of ascites recirculation (Rhodiascit apparatus) with the newly proposed method of daily paracentesis (3-4 litre) and intravenous albumin infusion. A mean of five (range 2-13) paracenteses removed 13.3 (2.0-36.0) l of ascites. 12 (5-32) h of recirculation produced 6.0 (2.0-12.0) l of waste. A significant diuresis occurred in 14 recirculation patients compared to four treated by paracentesis. No significant changes in electrolyte levels or renal function occurred. Complications were commoner with paracentesis (12) than with recirculation (5). Following recirculation, 18 patients were discharged after 7 (2-21) days; significantly (p less than 0.04) shorter than after paracentesis (11 (4-34) days, 16 discharges). Ascites reaccumulation and survival were identical in both groups. Fewer complications, shorter hospital stay and lower consumables costs (recirculation 240 pounds, paracentesis 400 pounds) make ascites recirculation an attractive therapeutic option to daily paracentesis and intravenous albumin in diuretic refractory ascites.

Adult↗
PubMed1990

Coagulation disturbances following ascites recirculation.

To investigate the effects of extra-corporeal ascites recirculation on coagulation, several coagulation variables were measured in ascitic return fluid and plasma before, during and after this procedure in 16 patients with diuretic resistant ascites. Small but significant reductions in plasma fibrinogen levels and platelet counts and increases in plasma X-oligomer were observed during and after the procedure compared with before. These findings are consistent with the view that ascites recirculation induces disseminated intravascular coagulation although this would appear to be only mild and of no clinical significance in the majority of patients. Although increased levels of activated factor VII were observed in ascitic fluid indicating activation of the extrinsic pathway of coagulation, a significant increase in plasma activated factor VII during the procedure was not demonstrated. Increased fibrinolytic activity was observed in ascitic fluid due to the presence of tissue plasminogen activator. Increased X-oligomer levels were observed in ascitic fluid indicating that lysis of cross-linked fibrin is also an active process within ascites.

Ascites↗