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E R Dickson

Publications and source records attributed to E R Dickson.

158 records · Page 9Linked to original sources
PubMedDate not supplied

Pathogenesis of steatorrhea in primary biliary cirrhosis.

To investigate the pathophysiology of steatorrhea in primary biliary cirrhosis, the severity of steatorrhea, small bowel histology and function, cholestasis, exocrine pancreatic secretion and liver histology were studied. Twenty-four primary biliary cirrhotic patients had a quantitative stool fat collection, serum bilirubin and alkaline phosphatase and liver biopsies. From this group, ten had further studies: a small bowel biopsy (n = 7); a D-xylose test (n = 9); measurement of pancreatiobiliary concentrations and outputs after intravenous cholecystokinin (n = 10); essential amino acid perfusion of the duodenum (n = 9), and eating a test meal (n = 7). D-xylose absorption was normal, and only one patient had a minimal small bowel mucosal abnormality. Pancreatic lipase outputs in response to cholecystokinin were low in two primary biliary cirrhotic patients, but were greater than 10% of normal. Postprandial lipase outputs were normal except in one patient who had abnormal duodenal acidification. Mean enzyme outputs in primary biliary cirrhotic patients were normal in response to essential amino acid perfusion; but 6 had low lipase and 5 had low trypsin outputs which were associated with decreased bile acid outputs (p less than 0.03). Severity of steatorrhea was associated with reduced bile acid outputs and concentrations (r = 0.82; p less than 0.0001), degree of cholestasis (serum bilirubin; r = 0.88; p less than 0.001) and advanced histologic stages (p less than 0.005). Severe intraluminal bile acid deficiency combined with a submaximal intraluminal stimulus (essential amino acids) may be associated with decreased exocrine pancreatic secretion in primary biliary cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMedDate not supplied

Primary biliary cirrhosis: associations with class II major histocompatibility complex antigens.

Tissue injury in primary biliary cirrhosis is thought to be mediated by immune mechanisms. Various Class II antigens of the major histocompatibility complex are associated with autoimmune diseases and their differing clinical manifestations. Thus, the aim of this study was to examine the relationship between primary biliary cirrhosis, its clinical manifestations and serologically defined Class II antigens (HLA-DR and HLA-DQ). Typing for these antigens was performed in 114 primary biliary cirrhotic patients and 171 controls by lymphocytotoxicity. There was a 6-fold increase in the frequency of HLA-DRw8 in primary biliary cirrhosis as compared to controls [30.1 vs. 4.7% (p less than 0.0001)]. In contrast, HLA-DR5 had a decreased frequency in primary biliary cirrhosis as compared to controls [9.8 vs. 25.2% (p less than 0.02)]. We examined the relationship between Class II antigens and the following prognostic indicators in primary biliary cirrhosis: serum bilirubin; 24-hr urine copper; serum albumin; prothrombin time; platelet count; ascites, and histologic stage (I to IV). Patients who are positive for HLA-DRw52 (n = 82) had a 2-fold increase in serum bilirubin compared to those who are negative (n = 32) for this antigen (p less than 0.05). Conversely, patients who are positive for HLA-DR2 had less than half the serum bilirubin values of those negative for this antigen (p less than 0.02). In conclusion, we found different Class II antigens to be associated with a prognostic indicator in primary biliary cirrhosis (serum bilirubin), while HLA-DRw8 is strongly associated with the disease itself.(ABSTRACT TRUNCATED AT 250 WORDS)

Bilirubin↗
PubMedDate not supplied

Clinical and statistical analyses of new and evolving therapies for primary biliary cirrhosis.

Primary biliary cirrhosis is a chronic, progressive, cholestatic liver disease thought to be related to abnormalities in immune regulation. The disease is associated with granulomatous bile duct destruction, cholestasis, hepatic copper overloading and the development of hepatic fibrosis or cirrhosis or both. There have been numerous therapeutic trials evaluating immunosuppressive, antifibrotic and cupruretic agents. Prednisolone, D-penicillamine, azathioprine, colchicine and chlorambucil have been evaluated in controlled clinical trials, and biochemical improvement of liver function has been noted with all of the agents, except D-penicillamine. Improved survival has also been reported in patients treated long-term with azathioprine and colchicine. However, none of the therapeutic agents has been demonstrated to halt histologic progression of the disease or to induce a complete clinical, biochemical and histologic remission as has been reported in patients with autoimmune chronic active hepatitis treated with corticosteroids. Many of the trials did not use a double-blind design, failed to use the "intent to treat" rule or failed to define an objective time to analyze results. Many of the studies involved small numbers of patients with short-term follow-up and thus potentially were inadequate to appreciate drug effects that might be of clinical benefit. Currently, there is no totally effective therapy for primary biliary cirrhosis. We believe that well-designed clinical trials can provide important information to better understand this disease until a totally effective therapy is available. New clinical trials should use well-established methodologic guidelines in study design and well-accepted statistical standards in the analysis and interpretation of results.

Adrenal Cortex Hormones↗
PubMedDate not supplied

The autologous mixed lymphocyte reaction in primary biliary cirrhosis: analysis of activation and blastogenesis of autoreactive T lymphocytes.

Blastogenesis of autoreactive T lymphocytes in the autologous mixed lymphocyte reaction has been shown to be decreased in patients with primary biliary cirrhosis, but the mechanisms underlying this abnormality are not known. To investigate further the abnormal autologous mixed lymphocyte reaction in primary biliary cirrhosis, we measured the activation of autoreactive helper/inducer and suppressor/cytotoxic T lymphocytes concurrently with blastogenesis in 35 patients with primary biliary cirrhosis and 18 healthy controls. Blastogenesis was diminished in autologous mixed lymphocyte reaction cultures from primary biliary cirrhosis patients compared to the control subjects (25,273 +/- 20,259 dpm vs. 36,004 +/- 14,951 dpm, p less than 0.02), but cultures from patients with primary biliary cirrhosis contained significantly increased percentages of activated helper/inducer and suppressor/cytotoxic T lymphocytes: 20.6 +/- 7.9 vs. 15.5 +/- 5.3%, p less than 0.008, and 9.8 +/- 7.8 vs. 5.4 +/- 3.0%, p less than 0.02, respectively. These findings were not related to the histologic stage of liver disease or to the serum bilirubin concentration and were not associated with abnormalities of lymphocyte subsets in fresh peripheral blood specimens. We conclude that the percentage of autoreactive T lymphocytes in autologous mixed lymphocyte reaction cultures from peripheral blood is increased in patients with primary biliary cirrhosis and diminished blastogenesis in autologous mixed lymphocyte reaction cultures is not due to the loss of autoreactive T lymphocytes from peripheral blood. Diminished blastogenesis reflects a diminished proliferative response of activated, autoreactive T lymphocytes in primary biliary cirrhosis. Possible mechanisms that may account for the paradoxical findings of decreased blastogenesis and increased activation of autoreactive T lymphocytes in primary biliary cirrhosis are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Rates of cancellous bone remodeling and turnover in osteopenia associated with primary biliary cirrhosis.

Osteoporosis and fracturing are well-recognized manifestations of primary biliary cirrhosis (PBC), but the abnormalities of bone remodeling and turnover that result in bone loss are poorly understood. We used dynamic histomorphometric techniques to measure tissue level rates of cancellous bone resorption, formation, and turnover in 12 premenopausal women with PBC and in 12 normal premenopausal women. We compared these values with estimates of bone resorption and formation obtained concurrently in the same subjects by radiocalcium kinetics and biochemical markers. Rates of bone turnover were analyzed as a function of a risk score that reflects the severity of hepatic disease and cholestasis (Mayo proportional-hazards model). Positive correlations were observed between tissue level and whole skeletal estimates of bone remodeling. At the remodeling site (bone multicellular unit [BMU]), the depth of eroded lacunae was unaltered by PBC, but wall thickness was decreased. At the level of bone tissues, mean bone turnover was increased in PBC patients but varied widely and increased as hepatic disease and cholestasis worsened. We conclude that PBC causes a reduction in the volume of bone formed at the remodeling site and that the overall level of bone remodeling and turnover in PBC is strongly influenced by the severity of hepatic disease and cholestasis. We hypothesize that the rate of bone loss in PBC may be decreased by therapeutic agents that slow bone turnover, and that further bone loss may be halted by liver transplantation.

Adult↗
PubMedDate not supplied

The syndrome of primary biliary cirrhosis.

Primary biliary cirrhosis, a chronic systemic disease, likely involves a disturbance in the immune process. The significant alterations in copper metabolism in this disorder are, we believe, related to progressive intrahepatic cholestasis and impairment in normal hepatobiliary copper clearance. A trial of D-penicillamine treatment suggests that this drug may benefit some patients. However, enthusiasm for the drug's use must be tempered by the fact that it may adversely affect 20% of patients; also, data regarding therapeutic effectiveness are not definitive. Therefore, we recommend using D-penicillamine for primary biliary cirrhosis only in control trials.

Double-Blind Method↗
PubMedDate not supplied

The pharmacokinetics of D-penicillamine in man.

High performance liquid chromatography (HPLC), coupled with an amalgamated gold electrochemical detector, to measure plasma and urine concentrations of D-penicillamine, was used to determine the pharmacokinetics of this drug following both its intravenous and oral administration in doses of 800 mg. After iv administration, plasma elimination half-life (T 1/2 beta) was 62.7 +/- 5.3 min; plasma clearance (CI) 560.7 +/- 42.8 ml/min; volume of distribution (Vd), 57.0 +/- 9.3 l; and % D-penicillamine excreted within 24 h, 42.1% +/- 6.2%. Following oral administration, T 1/2 beta was 60.7 +/- 8.2 min, % D-penicillamine excreted within 24 h, 21.2 +/- 2.3%; and fraction of absorption (f) 41.2 +/- 5.5%. Urinary copper excretion paralleled urine and plasma D-penicillamine concentrations.

Copper↗
PubMedDate not supplied

Primary biliary cirrhosis: Dutch application of the Mayo Model before and after orthotopic liver transplantation.

BACKGROUND/AIMS: A retrospective study of primary biliary cirrhosis (PBC) was performed to study the Original Mayo Model for predicting survival by a Dutch data-set of patients, presentation of disease progression; assessment of liver transplantation, prediction of post-transplantation survival; and the addition of two laboratory variables to the Original Mayo Model. MATERIALS AND METHODS: Survival of 83 patients, 37 of whom underwent transplantation, were studied. Mean follow-up was 6.0 +/- 0.45 SEM years. Risk score at diagnosis, platelet count, and serum sodium were analyzed in a Cox model. RESULTS: The Original Mayo Model estimated survival for low-, medium-, and high-risk groups accurately and it also presented disease progression. Baseline Mayo risk score in a Cox model had a regression coefficient of 1.01, indicating an excellent predictor p < 0.0001. Platelet count was a predictor of survival (p < 0.002), whereas serum sodium did not (p = 0.67). A new model combined of the Original Mayo risk score and platelet count predicted survival in high-risk patients somewhat better compared to the Original Mayo Model. With both models, liver transplantation had a significant beneficial effect on survival (p < 0.001). The scores revealed no significant influence (p = 0.47) for overall post-transplantation survival. CONCLUSIONS: The Original Mayo Model remains the model of choice for patients with PBC for prognostication from 3-8 years, is a useful tool in the assessment of liver transplantation but not an indicator of post-transplantation survival. Platelet count showed to have additional prognostic value. A new model combined of platelet count and the Original Mayo risk score did predict survival in high-risk groups slightly better compared to the Original Mayo Model.

Adult↗