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Biomedical subjects

W H Summerskill

Publications and source records attributed to W H Summerskill.

At least 37 records · Page 2Linked to original sources
PubMed1976

Abnormalities of chemical tests for copper metabolism in chronic active liver disease: differentiation from Wilson's disease.

Because identical clinical findings, alterations of hepatic function, and changes in hepatic morphology can occur in Wilson's disease (WD) and chronic active liver disease (CALD), chemical tests that reflect copper metabolism are important in the differential diagnosis of these conditions. The authors therefore measured 24-hr urinary copper excretion, hepatic copper concentration, and serum ceruloplasmin concentration in 54 patients with CALD. Twenty-four hour urinary copper excretion was increased in about 50% of patients, was significantly higher during active disease compared to remission, and was in the WD range in approximately 10% of patients. Hepatic copper concentration was also increased in the majority of patients, generally during active disease, and it sometimes overlapped with values reported in WD. By contrast, serum ceruloplasmin levels were elevated in nearly one-half the Cald patients and were never below normal. It is concluded that the chemical tests routinely used to assess copper metabolism in WD are frequently abnormal in CALD. Because the serum ceruloplasmin concentration never fell in the WD range and often was elevated, it is the most reliable routine chemical screening test to differentiate between CALD and WD.

Adolescent↗
PubMed1976

Measurement of gastric functions during digestion of ordinary solid meals in man.

A method of measuring gastric secretions and emptying rates after ingestion of an ordinary (solid-liquid) meal has been developed and validated. The technique quantifies movements of volume across the pylorus using constant duodenal perfusion with a nonabsorbable marker, polyethylene glycol (PEG), which, in turn, quantifies emptying into the duodenum of another marker, [14C]PEG, incorporated in the meal. Acid and pepsin outputs can be determined without manipulation of the intragastric pH. Employing this method, we have simultaneously quantified acid, pepsin, and total secretory outputs; rates of gastric emptying of meal and secretions; and serum gastrin levels during digestion. These data characterize physiological responses to ordinary food in health.

Adult↗
PubMed1976

Studies of the "e" antigen in acute and chronic hepatitis.

Sera from well individuals, including controls and asymptomatic HBsAg carriers, post-transfusion hepatitis cases, and chronic active liver disease patients were examined for the presence of "e" antigen and e antibody by rheophoresis. Our data confirm the specific association between the e determinant and hepatitis B infections and indicate that e antigen is closely associated with evidence of chronic hepatic dysfunction, in contrast to the association of e antibody with hepatic normalcy in HBsAg carriers. However, these correlations are not absolute and, therefore, it should not be inferred that all e antigen-positive individuals will develop chronic hepatitis nor, conversely, that presence of e antibody invariably protects against the development of chronic hepatitis.

Acute Disease↗
PubMed1976

Failure of customary treatment in chronic active liver disease: causes and management.

Among 134 patients with chronic active liver disease, selected by identical clinical, biochemical and morphologic criteria, assigned to standard treatment programs and followed at regular intervals, 21 of 105 failed treatment with standard regimens containing steroids. Treatment failure was more common in patients whose serum contained hepatitis B surface antigen, those with more severe liver disease as judged by liver function tests (prothrombin time) and hepatic morphology (subacute hepatitis or cirrhosis). Early diagnosis of treatment failure, based on changes in liver function tests rather than on clinical features of deterioration, coupled with the immediate administration of higher doses of prednisone with or without higher doses of azathioprine, resulted in disappearance of clinical and biochemical features of disease activity in the majority of patients. These results were greatly superior to those earlier reported by us from patients chosen by identical criteria but treated by conventional measures. However, when endogenous encephalopathy developed the outlook was grave, regardless of previous or subsequent therapy. We recommend that patients at risk for failing conventional treatment be identified early, followed carefully with serial liver function tests, and be treated promptly with higher doses of medication when deterioration occurs.

Azathioprine↗
PubMed1976

Effect of liquid diet on serum protein binding and prednisolone concentrations after oral prednisone.

After prednisone (two 5 mg tablets) was given to each of six normal volunteers with water or with a liquid meal, standard pharmacokinetic parameters of prednisolone metabolism were similar, except that peak serum prednisolone concentrations occurred later after the meal. We conclude that prednisone can be given with a meal without significantly affecting the metabolism of prednisone or prednisolone.

Administration, Oral↗
PubMed1976

Responses to treatment can differentiate chronic active liver disease with cholangitic features from the primary biliary cirrhosis syndrome.

Of 125 patients fulfilling preestablished criteria for severe chronic active liver disease (CALD) and enrolled in a prospective trial of treatment, 15 (12%) presented with morphological features of liver biopsy consistent with the diagnosis of both CALD and primary biliary cirrhosis (PBC) syndrome. Customary clinical, biochemical, and immunoserological studies failed to distinguish fully between these conditions. By contrast, early response to treatment with prednisone and/or azathioprine identified two different groups of patients. Five patients failed to respond, whereas 10 improved and this was followed by resolution of all clinical, biochemical, and morphological evidence of disease activity. Analysis of the initial chemical findings and cumulative bile duct counts from multiple biopsies correlated failure to respond with biochemical and morphological features more consistent with PBC than CALD. Responses to treatment can therefore be utilized when indicated for differentiating CALD with cholangitic features from PBC.

Adolescent↗
PubMed1976

Lymphocyte cytotoxicity and inhibition studied with autologous liver cells: observations in chronic active liver disease and the primary biliary cirrhosis syndrome.

A method is described for determining the cytotoxicity of normal and autologous lymphocytes for 51Cr-labeled isolated parenchymal liver cells in a low aggressor to target cell ratio. Results were compared from patients with chronic active liver disease (CALD), chronic persistent hepatitis (CPH), miscellaneous liver diseases, or primary biliary cirrhosis (PBC). In 53% of CALD patients, lymphocytes showed greater cytotoxicity for hepatic cells than did normal allogenic lymphocytes, but in 32% there was significantly less 51Cr release than normal; in the remainder, results were in the normal range. Lymphocyte cytotoxicity was greater in patients with disease of short duration and less in those treated with corticosteroids. In untreated CALD, decreased 51Cr release was associated with the presence of plasma factor(s) inhibiting phytohemagglutinin (PHA)-induced transformation of normal lymphocytes. Lymphocytes from approximately 50% of the patients with PBC exhibited cytotoxicity for hepatic cells but 25% showed less 51Cr release than controls and the remaining patients had results in the normal range. Lymphocyte cytotoxicity was also greater during the earlier stage of PBC. In contrast to CALD, decreased 51Cr release was not associated with the presence of plasma factor(s) inhibiting PHA-induced transformation of normal lymphocytes. Our findings support the hypothesis of in vivo lymphocyte-mediated liver cell damage in CALD and PBC, suggesting a potentially important role for lymphocyte suppression in the pathogenesis of both diseases.

Adult↗
PubMed1976

Development of radioimmunoassays for prednisone and prednisolone. Application to studies of hepatic metabolism of prednisone.

Radioimmunoassays for measuring prednisone and prednisolone (delta1 corticosteroids) in serum have been developed. By using 6,7-3H-delta1 corticosteroids as tracer, rabbit antibodies against delta1 corticosteroid-21-hemisuccinate in bovine serum albumin, and ammonium sulfate precipitation, the assays detected less than 0.8 ng/ml of delta1 corticosteroid and interassay coefficients of variation were less than 8.5 %. The specificity of antibodies, tested against all drug metabolites and major endogenous steroids, showed that only 21-glucuronic acid esters of delta1 corticosteroids had cross-reactivity of possible clinical importance. Assays were validated by measuring levels in samples of fastingstate sera with or without adding known amounts of prednisolone. Measurements of serum concentrations of both prednisone and prednisolone in normal dogs and in those with hepatic vascular exclusion were made after intravenous administration of prednisone. Although high levels of prednisolone appeared rapidly in normal dogs, only slight amounts were measured in dogs with hepatic vascular exclusion, which emphasized the importance of the liver in the conversion of prednisone to prednisolone, its active metabolite.

Animals↗
PubMed1975

Prednisone for chronic active liver disease: dose titration, standard dose, and combination with azathioprine compared.

Among 120 consecutive patients with chronic active liver disease (CALD) randomized to different treatments, those receiving maintenance doses of prednisone 20 mg daily (Pred), prednisone in doses given on alternate days and titrated to secure resolution of clinical and biochemical abnormalities (Pred-Titrad), or a combination of prednisone 10 mg and azathioprine 50 mg daily (Comb) survived and underwent resolution of clinical and biochemical features of disease more often than a control group receiving placebo or azathioprine 100 mg daily. Histological remission occurred significantly more often with Pred and Comb than with other regimens. Major side-effects of therapy were commoner with Pred than with Comb or Pred-Titrad, which did not differ. We conclude that Comb is the initial treatment of choice for CALD, since clinical, biochemical, and histological resolution of disease activity occurs as often as with Pred, whereas early side-effects are significantly less frequent.

Adolescent↗
PubMed1975

Omental arteriovenous fistula following liver biopsy.

A case of iatrogenic omental arteriovenous fistula attributable to an earlier unsuccessful liver biopsy is presented. The complications of liver biopsy and the role of arteriography in the diagnosis and management of visceral arteriovenous fistulas are discussed.

Adult↗