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Biomedical subjects

D R Triger

Publications and source records attributed to D R Triger.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Carbohydrate deficient transferrin: a marker for alcohol abuse.

OBJECTIVE: To assess the value of serum carbohydrate deficient transferrin as detected by isoelectric focusing on agarose as an indicator of alcohol abuse. DESIGN: Coded analysis of serum samples taken from patients with carefully defined alcohol intake both with and without liver disease. Comparison of carbohydrate deficient transferrin with standard laboratory tests for alcohol abuse. SETTING: A teaching hospital unit with an interest in general medicine and liver disease. PATIENTS: 22 "Self confessed" alcoholics admitting to a daily alcohol intake of at least 80 g for a minimum of three weeks; 15 of the 22 self confessed alcoholics admitted to hospital for alcohol withdrawal; 68 patients with alcoholic liver disease confirmed by biopsy attending outpatient clinics and claiming to be drinking less than 50 g alcohol daily; 47 patients with non-alcoholic liver disorders confirmed by biopsy; and 38 patients with disorders other than of the liver and no evidence of excessive alcohol consumption. INTERVENTION: Serial studies performed on the 15 patients undergoing alcohol withdrawal in hospital. MAIN OUTCOME measure--Determination of relative value of techniques for detecting alcohol abuse. RESULTS: Carbohydrate deficient transferrin was detected in 19 of the 22 (86%) self confessed alcohol abusers, none of the 47 patients with non-alcoholic liver disease, and one of the 38 (3%) controls. Withdrawal of alcohol led to the disappearance of carbohydrate deficient transferrin at a variable rate, though in some subjects it remained detectable for up to 15 days. Carbohydrate deficient transferrin was considerably superior to the currently available conventional markers for alcohol abuse. CONCLUSION: As the technique is fairly simple, sensitive, and inexpensive we suggest that it may be valuable in detecting alcohol abuse.

Alcoholism↗

Anorectal varices, haemorrhoids, and portal hypertension.

In a prospective study of 100 consecutive patients with cirrhosis, 44% had anorectal varices. The prevalence of anorectal varices rose with progression of portal hypertension; it was 19% in cirrhotic patients without portal hypertension compared with 59% in those who had bled from oesophageal varices. There was no evidence that endoscopic sclerotherapy directly increased the prevalence of anorectal varices. Haemorrhoids occurred independently of anorectal varices and their presence was unrelated to the degree of portal hypertension. These data provide further evidence that haemorrhoids and anorectal varices are separate and distinct entities. However, both can bleed and careful examination is essential to prevent misdiagnosis and inappropriate treatment.

Adult↗

Management of bleeding varices in the elderly.

In 207 consecutive patients the outcome of bleeding varices was compared in those aged under 65 (n = 146) and those aged over 65 (n = 61). All patients were seen during seven years and were treated by active initial and maintenance sclerotherapy. Alcoholic cirrhosis was commoner in younger patients (68 (47%) v 12 (20%] and cryptogenic cirrhosis commoner in older patients (21 (34%) v 19 (13%]. Mortality due to the first bleed was dependent on the severity of liver disease and was unrelated to age. Survival corrected for age (life table analysis) was 65% at one year and 60% at two years for both groups of patients. It is concluded that patients should not be denied active treatment for bleeding varices on the basis of age alone. In order to obtain optimum results early endoscopy and sclerotherapy is essential.

Aged↗

Trace element levels in the blood of workers in two steel works and a non-ferrous plant handling lead and cadmium compared with a non-exposed population.

The concentrations of 14 elements in the blood of steelworkers and industrial workers exposed to lead- and cadmium-containing dusts were measured and compared with a control group drawn from University and hospital laboratory staff. Measurements were also made of the concentrations of 20 elements in the dusts. Significantly elevated levels were observed for cadmium and lead in whole blood, but no other significant variations were noted. The concentrations of these two elements in the dusts confirmed the exposure of those groups showing high levels of cadmium and lead. High levels of iron or chromium in some of the dusts were not correlated with any changes in the mean blood levels of the exposed groups.

Air Pollutants, Occupational↗

Autoimmune chronic active hepatitis and primary biliary cirrhosis.

Autoimmune CAH is important to recognize, since it is highly responsive to treatment which undoubtedly prolongs life. Autoimmune CAH can rarely be cured; complete withdrawal of treatment leads to relapse in over 80% of patients. Prednisolone and azathioprine are the major drugs of choice, the former inducing remission while the latter maintains remission, either alone or in combination with prednisolone. Since both drugs are associated with substantial side-effects which tend to be dose-related, the object of treatment must be to induce and maintain remission with the minimum risk of relapse together with an acceptably low incidence of complications. Although PBC shares many features in common with autoimmune CAH, treatment of the underlying disease is generally unsuccessful. To date no drug has been shown to induce remission or to prolong survival. The main aim of treatment should be directed towards the complications of PBC, of which pruritus and osteoporosis are the two major complaints. Cholestyramine and antihistamines are the drugs of choice, but when these fail a variety of other therapies are also available, although many have only been shown to be effective on an anecdotal basis. No treatment has yet been shown to reverse the bone demineralization which occurs in PBC, but early calcium supplementation is recommended in this disorder. Osteomalacia is uncommon and can be prevented by prophylactic calcium and vitamin D supplementation in jaundiced patients. Liver transplantation is effective in treating PBC, and when successful leads to complete restoration of health with the prospects of increasingly long survival. Recurrence of PBC does not appear to be a significant problem.

Anti-Inflammatory Agents↗

Hepatic reticulo-endothelial function: a correlation of radioisotopic and immunohistochemical assessment.

Using an immunoperoxidase staining technique for muramidase (lysozyme)-containing cells in liver biopsies, the Kupffer cell population has been compared with the isotope liver scan abnormalities in 43 patients with various liver diseases. A significantly greater degree of scintigraphic abnormality was seen in cirrhotics compared with non-cirrhotics using both a visually assessed scan scoring technique (p less than 0.001) and computer-generated spleen-to-liver (S-L) relative activity ratios (p less than 0.01). The mean muramidase-positive cell count in cirrhotic biopsies was not significantly different from that in non-cirrhotics, neither was there any significant difference between alcoholic and non-alcoholic liver disease. The liver mass was shown to be significantly greater (p less than 0.02) in alcoholic compared with non-alcoholic disease, but even if corrections were made for this, no significant differences were found. A significant (p less than 0.02) negative correlation was found between liver scan score and muramidase-positive cell count in patients with cirrhosis but not in non-cirrhotic disorders. No significant correlations were observed if the computer-derived liver mass was taken into consideration. These results suggest that the scan defect seen in liver disease cannot be explained by loss of Kupffer cells alone, although they are consistent with the hypothesis that intrahepatic shunting plays a significant role. Chronic alcohol ingestion does not in itself appear to be a major independent influence.

Adult↗