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Biomedical subjects

E R Dickson

Publications and source records attributed to E R Dickson.

At least 109 records · Page 6Linked to original sources
PubMed1989

Prognosis in primary biliary cirrhosis: model for decision making.

The ideal mathematical model for predicting survival for individual patients with primary biliary cirrhosis should be based on a small number of inexpensive, noninvasive measurements that are universally available. Such a model would be useful in medical management by aiding in the selection of patients for and timing of orthotopic liver transplantation. This paper describes the development, testing and use of a mathematical model for predicting survival. The Cox regression method and comprehensive data from 312 Mayo Clinic patients with primary biliary cirrhosis were used to derive a model based on patient's age, total serum bilirubin and serum albumin concentrations, prothrombin time and severity of edema. When cross-validated on an independent set of 106 Mayo Clinic primary biliary cirrhosis patients, the model predicted survival accurately. Our model was found to be comparable in quality to two other primary biliary cirrhosis survival models reported in the literature and to have the advantage of not requiring liver biopsy.

Decision Making, Computer-Assisted↗
PubMed1989

Antimitochondrial autoantibodies in primary biliary cirrhosis recognize cross-reactive epitope(s) on protein X and dihydrolipoamide acetyltransferase of pyruvate dehydrogenase complex.

Antimitochondrial autoantibodies are characteristically present in sera of patients with primary biliary cirrhosis. The antimitochondrial autoantibodies recognize four major antigens from beef heart mitochondria at relative molecular weights of 74, 56, 52 and 48 kD. In the present study, we report that the 56 kD antigen is the protein X of pyruvate dehydrogenase complex and that it possesses cross-reactive antimitochondrial autoantibody epitope(s) with the 74 kD antigen, the acetyltransferase (E2) of the pyruvate dehydrogenase complex. This was demonstrated by comparing the specificities of primary biliary cirrhosis sera with a protein X-specific rabbit antiserum and by absorbing primary biliary cirrhosis sera with recombinant pyruvate dehydrogenase-E2 fusion protein. In the two-dimensional gel analysis, primary biliary cirrhosis sera and protein X-specific rabbit antiserum reacted to the same two isoelectric point polypeptides at 56 kD molecular weight. The absorption of primary biliary cirrhosis sera with the human recombinant pyruvate dehydrogenase-E2 removed reactivity toward both the 74 and 56 kD antigens. Furthermore, analysis of 82 antimitochondrial autoantibody-positive primary biliary cirrhosis sera by immunoblotting did not reveal any sera which reacted solely against either the 74 or 56 kD antigen. Finally, primary biliary cirrhosis sera recognized protein X from human, bovine and porcine sources but not protein X from rat or mouse origin. The identification of protein X as another major target of the autoimmune response in primary biliary cirrhosis suggests that the pyruvate dehydrogenase complex may have a central role in the induction of this enigmatic disease.

Acetyltransferases↗
PubMed1989

Primary sclerosing cholangitis: natural history, prognostic factors and survival analysis.

The natural history of primary sclerosing cholangitis was assessed in 174 patients; 37 were asymptomatic and 137 had symptoms related to underlying liver disease. At the time of diagnosis, the mean age was 39.9 years, 66% of the primary sclerosing cholangitis patients were male and 71% had associated inflammatory bowel disease, most commonly chronic ulcerative colitis. Long-term follow-up (mean: 6.0 years; range: 2.7 to 15.5 years) was available in all patients. During follow-up, 59 (34%) of the patients died: 55 in the symptomatic group and four in the asymptomatic group. Median survival from the time of diagnosis of primary sclerosing cholangitis at the Mayo Clinic was 11.9 years. Survival in the asymptomatic group was significantly decreased compared with that in a control population matched for age, race and sex. Multivariate analysis (Cox proportional hazards regression modeling) revealed that age, serum bilirubin concentration, blood hemoglobin concentration, presence or absence of inflammatory bowel disease and histologic stage on liver biopsy were independent predictors of high risk of dying. The development of a multivariate statistical survival model is a major step in identifying individual primary sclerosing cholangitis patients at low, moderate and high risk of dying. Such models will be useful for stratifying patients in therapeutic trials, in patient counseling and in patient selection and timing of liver transplantation.

Adult↗
PubMed1989

Extramural cross-validation of the Mayo primary biliary cirrhosis survival model establishes its generalizability.

The generalizability of the Mayo model for predicting survival in individual primary biliary cirrhosis patients without liver transplantation was tested and confirmed. The model was applied to a data base of patients from the New England Medical Center Hospitals (n = 141) and the Scott and White Clinic (n = 35) and found to predict their survival accurately. It was also shown to be accurate for Mayo primary biliary cirrhosis patients with very advanced disease (n = 30), those with less than a 33% chance of surviving 12 months. The analyses confirmed that the addition of histologic stage did not significantly improve the predictive power of the model (p greater than 0.10). We suggest that the Mayo model is a practical tool for clinical management and decision making.

Academic Medical Centers↗
PubMed1989

Prospective evaluation of esophageal varices in primary biliary cirrhosis: development, natural history, and influence on survival.

The aims of our prospective study were to determine the development and natural history of esophageal varices and variceal bleeding in patients with primary biliary cirrhosis. As part of a controlled clinical study, 265 patients with primary biliary cirrhosis who did not have esophageal varices at entry were followed for a median of 5.6 yr. The mean age was 49 yr (range 26-75 yr), 89% were women, and 69% had advanced histologic stage disease (stage 3-4) on liver biopsy at study entry. All patients were screened annually for esophageal varices by barium esophogram or endoscopy, or both; endoscopy was used to diagnose all episodes of esophageal variceal bleeding. Esophageal varices developed in 83 (31%) patients, and 40 (48%) of those with esophageal varices experienced one or more episodes of esophageal variceal bleeding. Cox regression analysis indicated that only serum bilirubin and histologic stage were associated independently with time to development of esophageal varices. In patients who developed esophageal varices, 33% and 41% developed esophageal variceal bleeding at 1 and 3 yr, respectively. After development of esophageal varices, 1- and 3-yr survival estimates were 83% and 59%, respectively. After the initial variceal bleeding episode, survival estimates were 65% and 46% at 1 and 3 yr and were dependent on Child's classification. These findings are important in considering indications for prophylactic therapy for esophageal varices in primary biliary cirrhosis and may influence timing of liver transplantation.

Adult↗
PubMed1989

Hepatoportal arteriovenous fistula: morphologic features studied after orthotopic liver transplantation.

A 51-year-old woman underwent orthotopic liver transplantation because of a small-duct primary sclerosing cholangitis associated with chronic ulcerative colitis and a hepatoportal arteriovenous fistula. Arteriograms before liver transplantation and specimen arteriograms revealed a convolution of arteries in the right hepatic lobe which communicated with a massively dilated and partly thrombosed portal vein branch. The lesion was probably the result of a previous liver biopsy. Microscopic examination of the fistula and of specimens taken at a distance from the fistula showed prominent intimal fibroplasia of portal vein branches. The vascular changes were so severe that hepatic artery and portal vein branches closely resembled each other on routine sections. We are unaware of such a finding in other conditions and therefore believe that recognition of the described vascular abnormalities in liver biopsy specimens should lead pathologists to comment that an arterioportal fistula might be present.

Angiography↗
PubMed1989

Application of the Mayo primary biliary cirrhosis survival model to Mayo liver transplant patients.

Liver transplantation is considered lifesaving for selected patients with end-stage primary biliary cirrhosis (PBC). A mathematical model to predict survival in the patient with PBC who has not undergone transplantation would be valuable for improving selection of patients for and timing of transplantation and for providing control information for assessment of the efficacy of transplantation. The Cox regression method and data from 312 Mayo Clinic patients with PBC were used to develop a model based on age, total serum bilirubin, serum albumin, prothrombin time, and severity of edema. When cross-validated on an independent set of 106 Mayo patients, the model accurately predicted their survival. It was similar to two other published survival models in terms of risk measurement but had the advantage of not necessitating liver biopsy. The model was used to assess the efficacy of liver transplantation by comparing the Kaplan-Meier survival of 32 Mayo patients after transplantation with the average model prediction of survival without transplantation. Beyond 3 months after transplantation, Kaplan-Meier survival probabilities were significantly greater than control survival predicted by the model (P less than 0.001). Examples of using the model for aiding in selection of patients for and timing of transplantation are provided.

Age Factors↗
PubMed1987

Primary biliary cirrhosis and the CREST syndrome: a report of 22 cases.

The syndrome of primary biliary cirrhosis and limited scleroderma (the CREST syndrome) is described in 22 patients. The syndrome is expanded to include a serologic marker--the anticentromere antibody--and keratoconjunctivitis sicca. The acronym 'PACK' (primary biliary cirrhosis, anticentromere antibody, CREST syndrome, and keratoconjunctivitis sicca) with 'syndrome' is suggested to facilitate recall of the various components of this entity.

Adult↗
PubMed1987

Human liver and conjugation of catecholamines.

To investigate the role of the liver in conjugation of catecholamines we measured the concentrations of free and conjugated norepinephrine, epinephrine, and dopamine in plasma of patients with severe liver disease who were undergoing liver transplantation. Comparisons were made with catecholamine levels in plasma of euhepatic patients who were undergoing abdominal aortic aneurysmectomy. We were also able to determine the importance of the liver in conjugation of exogenous dopamine because this compound was given to both groups of patients. The concentrations of conjugated amines were within the normal range in the patients undergoing liver transplantation, and administered dopamine was conjugated to a similar extent in the two groups of patients. The data suggest that the liver is not indispensable for the conjugation of circulating catecholamines.

Adult↗
PubMed1986

Frequency and significance of antimitochondrial antibodies in severe chronic active hepatitis.

Of 187 patients with severe chronic active hepatitis, 37 (20%) had antimitochondrial antibodies, usually of low titer (less than or equal to 1:40). To assess the significance of this finding and to identify differentiating features from primary biliary cirrhosis, 24 of these patients were compared to two groups of matched counterparts of which one lacked antimitochondrial antibodies and one had the antibodies together with typical primary biliary cirrhosis. Higher serum levels of alkaline phosphatase and an increased frequency of stainable hepatic copper were the only features that distinguished these patients from those without antimitochondrial antibodies. The response to corticosteroids was not influenced by antibody status. Histologic interpretation differentiated primary biliary cirrhosis from antibody-positive chronic active hepatitis in 91% of instances. High antibody levels (greater than or equal to 1:160), immunoglobulin M concentrations (greater than or equal to 6.0 mg/ml), alkaline phosphatase activity (greater than or equal to fourfold normal), and cholesterol elevations (greater than or equal to 300 mg/dl) separated the syndromes in 82% of instances. Patients with laboratory features of primary biliary cirrhosis but histologic findings of chronic active hepatitis responded to corticosteroids. We conclude that low titers of antimitochondrial antibodies are common in chronic active hepatitis, and the presence of these antibodies does not preclude a satisfactory response to corticosteroids. Histologic features are more reliable than biochemical findings in differentiating the syndromes and should be the basis for diagnosis and treatment.

Adrenal Cortex Hormones↗
PubMed1986

An association between HLA DRI and lichen planus.

Serological typing for HLA Class II antigens in 72 patients with lichen planus (LP) revealed a highly significant association with HLA DRI and MTI (DQWI). DRI was present in 80% of patients with generalized LP, 54% with localized LP, 56% of patients with drug-induced LP and in 31% of patients with mucosal LP, compared with 25% of normal controls. MTI (DQWI) was found in 83% of the LP group and 62% of the normal controls. These findings strongly suggest a genetic predisposition or susceptibility to the development of generalized LP and perhaps also to drug-induced LP.

Adult↗
PubMed1986

Primary thrombocythaemia treated with busulphan.

Thirty-seven patients with primary thrombocythaemia (PT) treated with busulphan have been followed for periods up to 25 years. Reduction of the platelet count to less than 400 X 10(9)/l resolved vascular occlusive symptoms, but haemorrhagic symptoms often remained unaltered. Cox regression analysis indicated that there were only two prognostically important presenting features; age had a strong inverse correlation with survival and vascular occlusive symptoms correlated with a better survival. Median duration of survival on treatment was 9 X 8 years. The number of deaths was 2 X 1 times that of a comparable control group, with deaths from myelofibrosis markedly increased. Deaths from thrombosis and malignant diseases, including leukaemia, were not significantly different from the number expected, which emphasizes the efficacy and the relative safety of busulphan for the long-term treatment of PT. Progression of PT into myelofibrosis occurred in 24% of cases and 9% became polycythaemic. Two additional cases of "thrombocythaemia' with a Philadelphia chromosome (and no overt evidence of chronic granulocytic leukaemia) are also presented.

Adult↗
PubMed1985

Trial of penicillamine in advanced primary biliary cirrhosis.

A total of 227 patients with histologically advanced primary biliary cirrhosis entered a double-blind, randomized, controlled trial to determine whether penicillamine (1 g per day) was therapeutically effective; 111 patients received the drug, and 116 received placebo. The two groups were highly comparable at entry with regard to clinical, biochemical, and histologic features. Penicillamine therapy did not result in an overall improvement in survival as compared with placebo. Clinical symptoms and serial hepatic laboratory values reflected the progressive nature of the disease and were similar in both groups. There were no substantial differences between treatment groups in the morphologic features of sequential biopsy specimens. The development of major side effects led to permanent discontinuation of penicillamine in 22 per cent of the patients taking the drug. We conclude that penicillamine is not useful for patients with histologically advanced primary biliary cirrhosis. The trial is being continued in patients with early histologic disease whose better prognosis necessitates longer follow-up.

Clinical Trials as Topic↗
PubMed1985

Comparison of the clinicopathologic features of primary sclerosing cholangitis and primary biliary cirrhosis.

Primary sclerosing cholangitis and primary biliary cirrhosis are chronic cholestatic syndromes that may be difficult to differentiate clinically. Destructive cholangitis occurs in both diseases and leads to similar clinical and biochemical abnormalities. Therefore, we compared the clinical, biochemical, immunologic, radiologic, and hepatic histologic features of these syndromes in two large groups of patients prospectively selected by predefined criteria. Primary biliary cirrhosis (n = 258) occurred predominantly in middle-aged women who were usually symptomatic with fatigue and pruritus, commonly had keratoconjunctivitis sicca, and often were hyperpigmented. Tests for antimitochondrial antibodies were always positive, usually in very high titer. Although the extrahepatic bile ducts were normal radiographically, smooth tapering and narrowing of the intrahepatic bile ducts was occasionally noted. Hepatic histology was diagnostic when a florid duct lesion was present. In contrast, primary sclerosing cholangitis (n = 60) occurred primarily in young men who were usually symptomatic with fatigue and pruritus and frequently had chronic ulcerative colitis. Tests for antimitochondrial antibodies were nearly always negative and cholangiography demonstrated abnormalities of the extrahepatic and intrahepatic bile ducts in all cases. Although hepatic histology was often compatible with the diagnosis, it was usually not diagnostic, and considerable overlap existed with the abnormalities seen in primary biliary cirrhosis. Likewise, biochemical tests of copper metabolism were similar in both syndromes. These results call attention to the differences and similarities in the clinicopathologic features of these two cholestatic syndromes and provide a basis for a rational diagnostic strategy.

Adult↗
PubMed1985

Bone loss and reduced osteoblast function in primary biliary cirrhosis.

The association of bone loss with primary biliary cirrhosis is poorly understood. In 15 premenopausal female patients, only 2 of whom had fractures, mean bone mineral density was reduced at the lumbar spine but not at the midradius or distal radius. Bone loss was not statistically related to the duration or severity of liver disease. Urinary hydroxyproline excretion, an index for bone resorption, was not different from that of 15 age-matched normal women, but the serum concentration of bone Gla-protein (osteocalcin), a specific marker for bone turnover, was decreased (p less than 0.001). Bone histomorphometric examination in 13 patients showed no osteomalacia but a reduced bone formation rate despite normal values for fractional osteoblast-osteoid interface. The substantial early loss of trabecular bone is mediated by a severe reduction in osteoblast function, which may be caused by retained toxic substances associated with cholestasis.

Adult↗
PubMed1984

Antemortem diagnosis and short-term survival of a patient with Wilson's disease presenting as fulminant hepatic failure.

When Wilson's disease presents as fulminant hepatic failure, it may be extremely difficult to differentiate from other causes of hepatic insufficiency. A recently described diagnostic biochemical profile (elevated serum and urine copper levels, mild transaminase elevation, very high bilirubin levels, and low hemoglobin with intravascular hemolysis) was employed to diagnose this form of Wilson's disease prior to death in a young woman without Kayer-Fleischer rings and with a normal serum ceruloplasmin level. Since hepatic transplantation now offers a possible cure for this previously uniformly fatal form of Wilson's disease, it should be considered the treatment of choice for this disease entity. Combined with the availability of hepatic transplantation, this patient's temporary improvement and unusually long survival of four months further emphasizes the importance of this diagnostic profile in recognizing Wilson's disease quickly and accurately when it presents as fulminant hepatic failure.

Adult↗