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Biomedical subjects

W H Summerskill

Publications and source records attributed to W H Summerskill.

At least 19 recordsLinked to original sources
PubMed1979

Different gastric, pancreatic, and biliary responses to solid-liquid or homogenized meals.

We have compared responses to an ordinary solid-liquid (S) meal and to a homogenized (H) meal of identical composition (sirloin steak, bread, butter, ice cream with chocolate syrup, and water) by measuring simultaneously postprandial gastric, pancreatic, and biliary functions by marker-perfusion techniques. Responses to each (S or H) meals differed strikingly both in magnitude and pattern. S meals elicited a stronger early gastric secretory response (acid, pepsin, and volume) which compensated for faster initial emptying and resulted in higher gastric acidity and volume than after H meals. Further, nutrients ingested with S meals were emptied at a slower rate than H (as evidenced by a more gradual decline in intragastric buffer and osmolality, as well as time required for complete emptying of the meal). This, in turn, prolonged pancreatic and biliary responses since stimulation of these organs continued for as long as meal was delivered into the duodenum. However, early biliary outputs (gallbladder response) were less after S than H, probably because nutrients entered the duodenum more slowly and were initially diluted by rapidly emptying water. The physical characteristics of each meal (encompassing appearance, taste, and form of ingestion) probably accounted for early differences in digestive responses. Later, interactions between gastric (motor and secretory), pancreatic, and biliary functions played a major role. Our findings suggest that gastric, pancreatic, and biliary responses to liquid test meals introduced into the stomach may differ substantially from the presumably more physiological response to ordinary solid-liquid meals.

Adult↗
PubMed1979

Development and early prognosis of esophageal varices in severe chronic active liver disease (CALD) treated with prednisone.

The prevalence of gastroesophageal varices and gastrointestinal hemorrhage was determined in 124 patients with severe chronic active liver disease (CALD) receiving prednisone and followed regularly for up to 10 yr. Varices were demonstrated by contrast radiography in only 19 patients (15%). Ten had varices before therapy and nine developed them after 12-102 mo of observation (mean, 38 +/- 9 mo.). The likelihood of developing varices within 5 yr after therapy was 8% in all patients and 13% after documentation of cirrhosis. Hemorrhage from varices occurred in only 1 patient, who had varices and bled once before treatment. Bleeding from other sites was commoner in the presence of varices (P less than 0.025), but mortality was not increased by bleeding from any site. The probability of upper gastrointestinal bleeding was only 6% within 5 yr after therapy and the 5 yr survival was 93%. In severe CALD, varices are an uncommon initial finding and do not develop quickly or hemorrhage early after steroid therapy.

Adolescent↗
PubMed1978

Oral prednisone for chronic active liver disease: dose responses and bioavailability studies.

Serum concentrations of prednisolone were measured by radioimmunoassay after the administration of prednisone (10, 20, or 30 mg) by mouth to five healthy volunteers, five patients with severe chronic active liver disease (CALD), and five patients with CALD in remission induced by prednisone. Only minor differences were found between the groups and bioavailability was linearly related to the dose of prednisone (r = 0.993). After prednisone (10 mg) was given by mouth and by vein to similar groups of volunteers and 11 additional patients with CALD, bioavailability of oral prednisone approximated 100% of the intravenous dose and no differences were found in the pharmacokinetics of prednisolone. We conclude that prednisone is effectively absorbed and converted to prednisolone in health and CALD and find no pharmacological evidence that either drug would be superior to the other for treating CALD.

Administration, Oral↗
PubMed1978

Cell-mediated cytotoxicity in chronic active liver disease: a new test system.

An in vitro cytotoxicity system was developed for studying patients with chronic active liver disease using as the target cells 51Cr-labeled avian erythrocytes coated with cell membrane lipoprotein extracted from human liver and, as the aggressors, mononuclear cells from peripheral venous blood. Approximately 50% of 62 patients with chronic active liver disease showed cytotoxicity in this test system as did 5% of 100 apparently healthy controls. In addition, mild cytotoxicity was shown by 2 of 8 patients with the primary biliary cirrhotic syndrome and 2 of 17 persons with other liver diseases. No specific antibody was added to the test system and the cytotoxicity could be inhibited by free lipoprotein, antilipoprotein, and by aggregated Ig. Cytotoxicity also was abolished by the depletion from the mononuclear cells of cells phagocytic for iron filings. The effect of depletion of these phagocytic cells was not restored by the addition of 2-mercaptoethanol. These findings add further evidence that autoimmune responses to liver tissue occur in many patients with chronic active liver disease and, importantly, suggest also that these may occur in some apparently healthy people.

Adolescent↗
PubMed1977

Severe chronic active liver disease. Prognostic significance of initial morphologic patterns.

To determine the usefulness of recognizing the different morphologic patterns of chronic active liver disease (CALD), we compared clinical and biochemical features as well as responses to treatment in 32 patients with chronic active hepatitis (CAH); 36 with subacute hepatitis and bridging necrosis (SHB); 30 with subacute hepatitis and multilobular necrosis (SHMN); and 30 with cirrhosis and active hepatitis (Cirrh). The morphological lesions did not correlate with clinical or etiologic features. Patients with CAH had less severe biochemical abnormalities, entered remission more often, and failed to respond to treatment less frequently than those with SHMN or Cirrh. SHB and SHMN resembled each other in many regards and showed greater functional changes than CAH. Cirrhosis developed more often after SHMN than CAH and was associated with a poorer prognosis than CAH. Serial liver biopsies revealed all possible histologic transitions, with reduction of inflammation usually occurring in patients treated with steroids and extension of inflammation being more frequent in those not receiving these drugs. CAH, SHB, SHMN, and Cirrh, therefore, reflect the degree and extent of disease activity at any given time in CALD, rather than representing different conditions. Identification of the initial morphologic lesion is helpful because of differences in prognosis.

Adult↗
PubMed1977

HLA determinants in chronic active liver disease: possible relation of HLA-Dw3 to prognosis.

Thirty-eight patients with severe chronic active liver disease (CALD) were found to have a significantly higher frequency of HLA-Dw3 (68%) than 91 healthy controls (24%) (P less than 0;0001). The association of CALD was statistically significantly stronger with the D locus than with the B locus of HLA. The response to treatment was significantly worse in patients with HLA-Dw3 than in patients who lacked this antigen.

Adult↗
PubMed1977

Gastric secretion and emptying after ordinary meals in duodenal ulcer.

We have studied the gastric response to an ordinary solid-liquid meal in 12 patients with active duodenal ulcer and 8 healthy volunteers. Our method employs gastric and duodenal markers to quantify acid, pepsin, and volume outputs in response to the meal, without manipulating intragastric pH. Intragastric volume, rate of gastric emptying, delivery of acid into the duodenum, and serum gastrin response were also measured simultaneously. On a separate day, peak acid output in response to betazole (1.5 mg per kg subcutaneously) was determined. Our results indicate an inappropriately prolonged gastric secretory response to meals in duodenal ulcer disease, without a concomitant increase in peak postprandial secretory rates or an increase in serum immunoreactive gastrin levels. Further, the stomach in duodenal ulcer disease did not "retain" the additional acid secreted in the later postprandial period, and abnormally high rates of acid delivery into the duodenum occurred. Our data are consistent with a dual defect in the duodenal mechanisms regulating both acid secretion and acid delivery into the duodenum.

Adult↗
PubMed1977

Prednisone for chronic active liver disease: pharmacokinetics, including conversion to prednisolone.

To determine the effect of impaired liver function on conversion of prednisone to prednisolone, and to investigate the relationship of this to responses to treatment with prednisone, we measured serum prednisone and prednisolone by radioimmunoassay after 10 mg of prednisone was given by vein to 10 healthy volunteers, 6 untreated patients with severe chronic active liver disease (CALD), 10 patients with prednisone-induced remission of CALD, and 3 patients with CALD deteriorating despite treatment with prednisone. Prednisone disappearance was comparable in all groups and substantial values for serum prednisolone appeared in all groups within 0.3 hr. Minor differences between the groups included lower than normal serum prednisolone in severe CALD and treatment failure; a higher percentage of nonprotein bound prednisolone in such patients; and an association between earlier treatment with prednisone and an increased disappearance rate of prednisolone. We conclude that no major defect of prednisone metabolism occurs in CALD and that failure of this condition to respond to therapy with prednisone is caused by other factors.

Adult↗
PubMed1977

Participation of the jejunum and ileum in postprandial gastric secretion in man.

The role of the small intestine in postprandial gastric secretory function was determined in 6 normal volunteers by diverting chyme at the ligament of Treitz and comparing the results with those obtained in the same individuals when chyme was exposed to the entire small intestine. Because diversion of chyme caused a lesser gastric secretory response, it is concluded that the small intestine contributes appreciably to the magnitude of gastric secretory responses to meals.

Adult↗
PubMed1976

Behaviour of e antigen and antibody during chronic active liver disease. Relation to HB antigen-antibody system and prognosis.

Serial determinations of e antigen and e antibody were made in 20 patients with chronic active liver disease and hepatitis-B surface antigen (HBsAg) or antibody (anti-HBs). The presence of e antigen was associated with failure to clear HBsAg, produce anti-HBs, or respond to treatment with steroids. It is proposed that the presence of the e antigen is associated with impaired host immune responses to hepatitis-B virus infection and a poor prognosis.

Adolescent↗
PubMed1976

Contrasting features and responses to treatment of severe chronic active liver disease with and without hepatitis BS antigen.

To determine the clinical implications of HBSAg in severe chronic active liver disease (CALD), patients with HBSAg positive CALD were compared with those chosen by identical clinical, functional, and morphological criteria in whom this test and anti-HBS were negative. HBSAg positive patients were predominantly males over 40 years of age and more frequently failed to respond to conventional treatment programmes with prednisone. HBSAg negative patients were more often female and younger, had a higher incidence of associated immunopathic disease and immunoserological markers in high titre, and more often responded to treatment with full remission of their disease. HBSAg positive patients failing treatment with conventional doses of prednisone often improved with higher doses, but did not reach full remission of their disease. The benefit-risk ratio of both conventional and high doses of prednisone in HBSAg positive severe CALD needs further clarification.

Adult↗
PubMed1976

Regulation of pancreatic and gallbladder functions by intraluminal fatty acids and bile acids in man.

The effects of intraduodenal glycerol, fatty acid (FA) chain length and FA loads, and bile acid (BA) concentrations on pancreatic and gallbladder function were investigated in 31 healthy volunteers by a perfusion method. FA absorption rates in the duodenum and proximal jejunum were measured simultaneously. Pancreatic and gallbladder responses were augmented by increasing FA chain length and FA loads until the "maximal" secretory capacity of the pancreas and gallbladder emptying was attained. Glycerol had no effect. Raising BA concentrations above the critical micellar concentration accelerated FA absorption rates but decreased the magnitude of pancreatic and gallbladder responses to FA. Higher BA concentrations exerted an opposite effect, slowing FA absorption and increasing pancreatic and gallbladder responses. Indeed, a significant, inverse correlation was found between FA absorption and pancreatic and gallbladder responses to FA, suggesting a relationship between the length of intestine exposed to FA and the amount of cholecystokinin (and/or other neurohormonal factors) released, which stimulates pancreatic secretion and gallbladder contraction.

Adult↗
PubMed1976

Alpha1-antitrypsin phenotypes in chronic active liver disease and primary biliary cirrhosis.

Alpha1-antitrypsin concentrations and phenotypes were determined in groups of patients with chronic active liver disease and primary biliary cirrhosis. The concentrations of alpha1-antitrypsin were above normal values in both groups; the patients with primary biliary cirrhosis had higher concentrations than those with chronic active liver disease. The prevalence of common phenotypes in these two groups did not differ from that in a sample of healthy blood donors from this institution of from a large Norwegian sample. We interpret our data as disputing the view that alpha1-antitrypsin phenotypes, other than Z. significantly predispose adults to hepatic cirrhosis.

Adolescent↗
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↗