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Biomedical subjects

A P Douglas

Publications and source records attributed to A P Douglas.

At least 19 recordsLinked to original sources
PubMed1983

Effects of scorpion and rattlesnake venoms on the canine pancreas following pancreaticoduodenal arterial injections.

Three scorpion venoms caused a transitory decrease in the rate of fluid secretion and increases in the concentration, in pancreatic juice, of total protein and individual enzymes. Protein and enzyme elevations 4-7 fold over the basal levels were produced by the venom of Tityus bahiensis and 6-7 fold by venoms from Tityus serrulatus and Buthus quinquestriatus. Although these increases were smaller than those stimulated by the C-terminal octapeptide of cholecystokin (OP-CCK; 8-9 fold), the secretory responses were of longer duration, so that the total output of protein caused by each of the three venoms was significantly greater than that observed with OP-CCK. Although electron microscopy revealed evidence of widespread degeneration of acinar cells at 1 hr and more extensive damage at 2 hr following injection of scorpion venom, no free protease was detected in pancreatic secretion collected during this period. The scorpion venoms also caused hypersecretion of viscid saliva. In contrast, rattlesnake venom, had no detectable effect on salivation, pancreatic secretion or morphology of the pancreas.

Animals↗
PubMed1981

Tiotidine, a new H2-receptor antagonist, is a potent inhibitor of nocturnal acid secretion in duodenal ulcer patients.

The efficacy of tiotidine, a new H2-receptor antagonist, in reducing nocturnal acid secretion of duodenal ulcer patients (N = 12, ages 21-60 years) was investigated. Different doses of tiotidine, 25, 50, 100, and 150 mg or placebo, were given as a single oral dose and acid secretion collected overnight. Tiotidine produced a significant, prolonged, and dose-related reduction of the nocturnal acid secretion without important side effects. The inhibition of cumulative H+ secretion after 25, 50, 100, and 150 mg tiotidine was 80, 89, 96, and 98% of that observed after placebo, while 300 mg of cimetidine caused an 87% inhibition. Compared to cimetidine, tiotidine appears to be approximately eight times more potent on a molar basis than cimetidine as an inhibitor of acid secretion, and the tiotidine effect is more prolonged. This strong and safe H2-receptor antagonist may be an important addition to the treatment of acid hypersecretory states.

Adult↗
PubMed1980

Studies of pure pancreatic secretions in chronic alcoholic subjects without pancreatic insufficiency.

To determine the role alcohol might play in altering pancreatic function, we have examined pure pancreatic juice, obtained by endoscopic cannulation of the pancreatic duct, from a group of 10 chronic alcoholic subjects without history or clinical or laboratory evidence of pancreatic disease and compared the results with those obtained from 15 healthy, non-alcoholic subjects. These findings confirm observations in experimental animals made by others and support the hypothesis that chronic alcohol abuse may damage the pancreas via a sequence of events involving protein hypersecretion. Increase in concentration was not uniform for all proteins measured. Unexpectedly, chronic alcoholics exhibited a highly significant elevation (two- to three-fold over normal) in trypsinogen, in contrast to statistically insignificant increases of other zymogens and trypsin inhibitor. The strikingly increased ratio of trypsinogen to trypsin inhibitor observed in all our alcoholic patients may indicate a weakening of the defence mechanism provided by the trypsin inhibitor against premature intraductal activation of zymogens and explain the predisposition of these patients to pancreatitis.

Adult↗
PubMed1979

alpha-Amylase of human pure pancreatic juice: effects of pancreatic disease and the occurrence of variant forms in pancreatic juice from healthy volunteers.

Pure pancreatic juice (PPJ) from healthy human volunteers and from patients with pancreatic or liver disease was subjected to isoelectric focussing (IEF) and assayed for alpha-amylase activity. In PPJ from most normals, a single predominant form of amylase was found, comprising congruent to 83% of the total activity recovered, and having pIapp congruent to pH 6.8. In PPJ from six normals, variant principal forms of amylase were found at pH congruent to 6.4 or pH congruent to 7.3, in addition to the peak at pH 6.8. IEF patterns of PPJ from individuals with pancreatic or liver disease were indisquishable from patterns obtained with PPJ from the control group of healthy volunteers.

Amylases↗
PubMed1979

Highly purified basal lateral plasma membranes from rat duodenum. Physical criteria for purity.

Preparations of intestinal epithelial cell basal lateral plasma membranes were analyzed with free flow electrophoresis and density perturbation with digitonin. The initial basal lateral membrane preparations were obtained by equilibrium density gradient centrifugation after two different schemes of homogenization and differential sedimentation (A.K. Mircheff, C.H. van Os, and E.M. Wright. 1978. Membr. Biochem. 1:177, and A.K. Mircheff, S.D. Hanna, M.W. Walling, and E.M. Wright. 1979. Prep. Biochem. 9:33. In these preparations, Na,K-ATPase, a marker for the basal lateral mambrane, was purified 16- to 18-fold over the initial homogenate. The preparations were also enriched in NADPH-cytochrome c reductase, alkaline phosphatase, acid phosphatase, and galactosyltransferase. Both free-flow electrophoresis, which separates on the basis of surface charge, and density perturbation with digitonin, which depends on a specific interaction of digitonin with cholesterol-rich membranes, resolved the preparation into three populations of particles. The major population, which represented basal lateral membranes purified 20- to 32-fold with respect to the initial homogenate, contained Na,K-ATPase, alkaline phosphatase, adenylate cyclase, and acid phosphatase. A second population was defined by its content of NADPH-cytochrome c reductase, and the third was defined by its content of galactosyltransferase. Guanylate cyclase appeared to be partitioned between the Na,K-ATPase-rich and NADPH-cytochrome c reductase-rich populations. Galactosyltransferase is also present in fractions which contain the Na,K-ATPase-rich membranes, but the present data cannot exclude the possibility of spillover by the adjacent, galactosyltransferase-rich population. This work emphasizes the importance of multiple, physical criteria for purity in the isolation of subcellular components.

Animals↗
PubMed1978

Paracetamol (acetaminophen) kinetics in patients with Gilber's syndrome.

The pahrmacokinetics of paracetamol after intravenous and oral administration has been studied in 6 patients with Gilbert's syndrome, and 6 healthy controls. Paracetamol clearance was significantly less in the patients (255 ml/min SE +/- 23 ml/min) than in the normal subjects (352 ml/min SE +/- 40 ml/min). Moreover, whilst paracetamol concentrations declined monoexponentially in the patients, the decline was biexponential in the controls. No difference in the bioavailability of 500 mg paracetamol given orally was observed between the two groups. The results suggest that not only is paracetamol elimination impaired in Gilbert's syndrome, but that its distribution kinetics are also abnormal. Both these findings could be attributed to a decrease in hepatic glucuronyl transferase activity.

Acetaminophen↗
PubMed1978

The spectrum of paracetamol (acetaminophen) overdose: clinical and epidemiological studies.

In a regional survey of paracetamol overdose, 201 patients were admitted to hospital over 12 months. Chronic alcoholism was present in 10% of cases. Over 25% of patients were females aged 20 years or less. Initial blood paracetamol levels were in the toxic range in 16% and histologically severe liver damage eventually found in 20% of those biopsied. This finding corresponded to a serum aspartate aminotransferase of 600 i.u./l or more. Renal failure severe enough to require peritoneal dialysis developed in 1%. Elevated serum amylase was recorded in 22% of a 108-patient subset. Evidence of myocardial damage was found in 11.6% of an eighty-six patient subset. An unfavourable prognosis was indicated by a prothrombin ratio of 20% or less and hepatic coma, the overall mortality being 3.5%. The apparent safety of this useful analgesic is compromized by its widespread employment in parasuicide. This, the insidious and delayed onset of toxicity in overdose and ineffectiveness of late treatment argues for controlling availability to the general public.

Acetaminophen↗
PubMed1978

Profiles of pure pancreatic secretions in patients with acute pancreatitis: the possible role of proteolytic enzymes in pathogenesis.

Studies have been performed on pure pancreatic juice obtained by direct cannulation of the pancreatic duct in 2 patients with acute pancreatitis. The striking abnormalities observed, which were in marked contrast to our observations in 15 normal subjects, were high concentrations of protein throughout the period of secretin stimulation and the sporadic appearance of free proteolytic activity in many 1-min specimens throughout the collection period. In 1 subject repeat studies were performed after resolution of the pancreatitis when the profile observed was normal. Our findings are consistent with the hypothesis that obstruction of ductules and intraductal activation of zymogens may be important in the pathogenesis of acute pancreatitis.

Acute Disease↗
PubMed1977

Fulminant Wilson's disease with haemolysis and renal failure: copper studies and assessment of dialysis regimens.

Two girls, aged 12 and 17 years, presented with hepatocellular dysfunction and severe haemolysis due to Wilson's disease (hepatolenticular degeneration). This was accompanied by acute renal failure. In the absence of renal function sufficient for the urinary excretion of penicillamine, studies were performed to assess the potential of peritoneal dialysis, ascites removal by ultrafiltration-reinfusion, and haemodialysis as alternative excretory pathways for copper. The greatest amount of copper, as judged by rising bath concentrations, seemed to be eliminated with haemodialysis. But this was accompanied by a progressive increase in serum copper concentrations with rapid clinical and biochemical deterioration leading to death within 48 hours. A small amount of copper was lost with ascites removal. Significant amounts of copper were removed during peritoneal dialysis (36 mumol/day (2287 microgram/day)), although a clinical response was not evident before haemodialysis was introduced. The administration of penicillamine orally, intravenously, or intraperitoneally produced no measurable increase in copper excretion into the peritoneal dialysate. Hence peritoneal dialysis alone appears to offer the greatest potential benefit with regard to both eliminating copper and altering the course of this fulminant form of Wilson's disease.

Acute Kidney Injury↗
PubMed1977

Iron-transport characteristics of vesicles of brush-border and basolateral plasma membrane from the rat enterocyte.

Vesicles of brush-border and basolateral plasma membrane were prepared from enterocytes of the rat small intestine. The separateness of these two varieties of plasma membrane was confirmed by appropriate enzyme assays. The uptake of Fe2+ by these membrane vesicles was studied, and the results suggest differences between the two types of membrane in both the amount of Fe2+ taken up and in the rate of uptake. At low (up to 3 micrometer) concentrations of Fe2+, uptake by both membrane types showed evidence of saturation and could be blocked with the thiol inactivator N-ethylmaleimide. The studies suggest that Fe2+ is taken into an osmotically active space by a process of facilitated diffusion at low concentrations, but that at higher concentrations the process appeared to obey first-order kinetics. The data provide further evidence for the existence of functional polarity in the epithelial cell of the small intestine.

Animals↗
PubMed1977

Liver function and structure in survivors of acetaminophen poisoning. A follow-up study of serum bile acids and liver histology.

A series of 30 patients, hospitalized with acetaminophen overdose, were studied during initial admission and again three months later. The quantity of acetaminophen ingested varied from 5 to 50 g and 19 patients developed raised transaminase levels in the serum during the initial period. Liver damage, on the basis of needle biopsy findings, was categorized as severe in 5, moderate in 7, and mild or minimal in 18 patients. At three months' follow-up all but one of the biochemical indicants of liver damage had reverted to normal in all patients. The exception was the serum total bile acids. Residual changes found on liver biopsy at three months were minimal and nonspecific, apart from one previously severely affected patient in whom there was evidence of scarring. It is concluded that in the usual spectrum of acetaminophen poisoning requiring hospitalization there is no evidence of lasting liver damage.

Acetaminophen↗
PubMed1977

A comparative study of double contrast and single contrast barium meals with endoscopic arbitration in the diagnosis of peptic ulcer.

The study compares the ability of a simple double contrast technique with our standard single contrast barium meal to diagnose peptic ulceration. Two hundred and six patients were randomly allocated to either examination. Endoscopy was used as the definitive diagnostic procedure. Deformity of the duodenal cap was more accurately detected by the double contrast technique (P less than 0.01). There was no significant difference in the detection rates for duodenal ulcer. False positive or false negative diagnoses of duodenal pathology were similar by both techniques. The incidence of gastric ulceration in the series was too low for statistical analysis.

Adult↗
PubMed1976

The binding of a glycopeptide component of wheat gluten to intestinal mucosa of normal and coeliac human subjects.

A carbohydrate-containing component of wheat gluten (glyc-gli) has been prepared which is toxic to coeliac intestinal mucosa. Its amino acid composition is uniquely different from that of the parent gluten and from alpha-gliadin. This glyc-gli material has been shown to bind to membrane components of the coeliac intestinal cell but to bind only poorly to normal intestinal cell membranes. Furthermore this binding can be interfered with by exogenous free carbohydrate suggesting that the toxic moiety of gluten acts in an analagous way to plant lectins. These data suggest that the underlying defect in coeliac disease is related to the composition of the surface membrane of the enterocyte.

Amino Acids↗