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Biomedical subjects

V S Chadwick

Publications and source records attributed to V S Chadwick.

At least 109 records · Page 6Linked to original sources

Dose-related effects of chenodeoxycholic acid in the rabbit colon.

The effects of bile acid (BA) concentration on fluid secretion, mucus secretion, and mucosal damage were investigated during dose-response studies in the rabbit colon with 1, 2.5, and 5 mM sodium chenodeoxycholate (NaCDC). 1 mM NaCDC resulted in mucus secretion followed by mucosal damage but no change in fluid transport was observed. At 2.5 mM concentration, mucus secretion and mucosal damage were evident within 1 hr of perfusion whereas fluid secretion developed in the second hour only. At 5 mM concentrations, all changes occurred simultaneously. The magnitude of changes increased with the concentration of BA perfused. These results are consistent with the hypothesis that mucus secretion with loss of its cytoprotective effect precedes, and thus may permit, the detergent effects of the di-alpha-hydroxy bile acid on the mucosa, resulting in mucosal damage. Both these effects precede changes in fluid and electrolyte transport.

Animals↗

Malabsorption and macroamylasemia. Response to gluten withdrawal.

A 36 year old woman presented with malabsorption and macroamylasemia. The macroamylase was characterized and shown to be a complex of pancreatic amylase and immunoglobulin A(IgA). The patient had the clinical and histologic features of adult celiac disease, and responded to a gluten-free diet. The macroamylase complex disappeared from the serum after gluten withdrawal, a hitherto unreported finding in the syndrome of malabsorption and hyperamylasemia.

Adult↗

Treatment of haemobilia by selective arterial embolisation.

We report a patient in whom haemobilia occurred after percutaneous liver biopsy. Selective hepatic arteriography showed a fistula between hepatic artery and portal venous system, with appearance of contrast in the biliary tract. Intrahepatic bleeding was stopped by arterial embolisation with a mixture of gelatine foam and sterile dura mater. Cholecytectomy was subsequently required as a haemocholecyst developed. The technique of arteriography and embolisation allows accurate localisation of intrahepatic bleeding sites and may avoid the need for a direct surgical approach to this problem.

Biopsy, Needle↗

Effect of bovine pancreatic polypeptide on basal pancreatic and biliary outputs in man.

Basal pancreatic and biliary outputs were examined in seven healthy volunteers during intravenous infusion of bovine pancreatic polypeptide (BPP) at a mean dose of 320 pmol/kg/hr. BPP significantly (P less than 0.02) inhibited outputs of trypsin and bilirubin, without affecting bicarbonate. These studies suggest the possibility that pancreatic polypeptide may have a role in the regulation of biliary and pancreatic enzyme secretion in man.

Adult↗

Immunodeficiency, malabsorption and secretory diarrhea. A new syndrome.

Described here is a patient with severe watery diarrhea associated with common variable immunodeficiency. Malabsorption for fat, bile acids, vitamin B12 and xylose was demonstrated, but the patient failed to respond to all the usual therapeutic maneuvers. The diarrhea responded only to high dose steroid therapy. Intestinal perfusion studies showed a hitherto undescribed, presumably acquired, glucose-stimulated water, sodium and chloride secretion in the jejunum and ileum, whereas normal fluid and electrolyte transport occurred from bicarbonate and mannitol solutions. Glucose absorption itself was normal and no hormonal, morphologic or biochemical defect was demonstrated to account for the phenomenon. The patient was also interesting when compared with other patients with common variable immunodeficiency in having normal plasma cells in the intestinal mucosa and an extensive family involvement.

Adult↗

Effects of gastrointestinal hormones on fasting gallbladder storage patterns in man.

Gallbladder storage and emptying patterns were studied in fasting normal subjects by a duodenal perfusion technique using indocyanine green as a biliary marker. Fasting gallbladder storage patterns were very variable but a more uniform biliary output with net storage of about 40% of the biliary marker was observed during a simulated interprandial state (2--4 h after meals) produced by a low dose intravenous infusion of secretin and caerulein. With this background hormonal stimulation, infusion of bovine pancreatic polypeptide to achieve physiological interprandial levels promoted further gallbladder storage of bile. Bovine pancreatic polypeptide produced storage by a major effect on the gallbladder rather than on the liver, common bile duct or sphincter of Oddi since a reduction of biliary output was not observed during bovine pancreatic polypeptide infusion in cholecystectomized subjects. Bovine pancreatic polypeptide had a separate effect on the pancreas, reducing trypsin output in both normal and cholecystectomized subjects.

Adult↗

Rôle of calcitonin in diarrhoea associated with medullary carcinoma of the thyroid.

Severe watery diarrhoea in a patient with medullary thryoid carcinoma and high calcitonin levels was associated with increased distal ileal flow. Plasma from the patient inhibited small intestinal fluid absorption in dogs without affecting mucosal cyclic AMP levels. When calcitonin was removed from the plasma, the effect in experimental bowel loops was abolished but could be restored on restitution of comparable hormone levels with pure calcitonin. These studies, combined with the failure to find evidence of increased prostaglandin activity in the patient, suggest that circulating calcitonin may be a major cause of the diarrhoea in medullary thyroid carcinoma.

Animals↗

Liver and gastrointestinal function in pregnancy.

Difficulties arise in the interpretation of liver tests in the pregnant subject, since some values increase (alkaline phosphatase) whilst others remain unchanged (transaminases) or fall during pregnancy. The diagnosis and management of some causes of jaundice in pregnancy, such as viral hepatitis, gall stones, benign intrahepatic cholestasis and acute fatty liver of pregnancy are discussed. Little is known about the commonest symptoms of pregnancy (nausea, vomiting and constipation) other than that they might be due to hormonally induced alteration of sphincter tone. However, pre-existing bowel disease has a greater effect on pregnancy. Fertility is reduced in poor nutritional states (e.g. coeliac and Crohn's diseases) and an increased occurrence of spontaneous abortion has been noted. For inflammatory bowel diseases, the time of onset is important in determining the outcome of pregnancy. Relapse in the disease is commonest in the first trimester and in the puerperium. Treatment of these conditions is essentially as in the non-pregnant subject. The controversial subject of sulphasalazine and steroid usage in pregnancy is discussed.

Adult↗

Coeliac disease presenting with a leuco-erythroblastic anaemia.

A 49-year-old Irishman presented as an emergency with watery diarrhoea and a leuco-erythroblastic anaemia. Investigations showed that he had coeliac disease but no evidence of bone marrow infiltration. His leuco-erythroblastic picture disappeared on treatment with iron and folic acid.

Anemia, Myelophthisic↗

Effect of molecular structure on bile acid-induced alterations in absorptive function, permeability, and morphology in the perfused rabbit colon.

An in vivo intestinal perfusion system was used to study the effects of different bile acids on fluid secretion, mucosal permeability, and mucosal morphology in the rabbit colon. To define the structure-activity relationships of the bile acids, nine unconjugated bile acids were used, varying only in the number (two or three) or position (3, 7, or 12 or various combinations) of hydroxy or keto nuclear substituents. Results showed that bile acids with two hydroxy groups in the alpha configuration at the 3,7 position, 3,12 position, or 7,12 position induced fluid secretion, increased mucosal permeability, and produced mucosal damage as assessed by light and scanning electron microscopy and quantitated by DNA loss during perfusion. Replacement of hydroxy groups by keto groups or a change from alpha to beta configuration for the hydroxylic substituent in the 7 position abolished all three activities. Trisubstituted derivatives, whether hydroxy or keto, did not affect fluid secretion permeability or cause mucosal damage. These studies indicate that of the major primary and secondary bile acids in man, only deoxycholic and chenodeoxycholic acids alter colonic structure and function in the rabbit. They show further that the cathartic effects of bile acids have specific structural requirements; and they show that bile acid-induced secretion was invariably associated with increased mucosal permeability and epitheliolysis.

Animals↗

Inhibition of pancreas and gallbladder by pancreatic polypeptide.

Stimulated pancreatic and biliary outputs were studied in seven healthy subjects during intravenous infusion of bovine pancreatic polypeptide (P.P.) (mean dose 65 pmol/kg/h). P.P. significantly inhibited outputs of trypsin and bilirubin at plasma concentrations similar to those observed after meals. In four cholecystectomised subjects, P.P. inhibited only trypsin output.

Adult↗

Effect of sodium chenodeoxycholate on oxalate absorption from the excluded human colon--a mechanism for 'enteric' hyperoxaluria.

A perfusion technique has been used to study the effect of sodium chenodeoxycholate (5 mmol 1-1) on absorption of oxalate (2 mmol 1-1) from the surgically excluded colon in two patients with chronic liver disease. Colonic absorption of oxalate increased at least fivefold when sodium chenodeoxycholate was incorporated in the perfusion solutions. This observation may explain enteric hyperoxaluria after ileal resection and in some other gastrointestinal disorders.

Adult↗

Binding properties in vitro of antacids for conjugated bile acids.

The binding properties of various commercial antacids for pure conjugated bile acids in an aqueous solution or the bile acids present in human gallbladder bile were characterized. Aluminum hydroxide was a potent binding agent, similar in affinity and capacity to cholestyramine. With aluminum hydroxide, dihydroxy bile acid conjugates were bound more strongly than trihydroxy bile acid conjugates, and glycine conjugates were bound more strongly than taurine conjugates; pH had no effect per se on binding. Magnesium hydroxide and aluminum phosphate bound bile acids much more weakly. Aluminum hydroxide warrants exploration in therapeutic situations in which bile acid binding is sought.

Aluminum↗

Perfusion of rabbit colon with ricinoleic acid: dose-related mucosal injury, fluid secretion, and increased permeability.

Morphology of the rabbit colon was examined by light and scanning electron microscopy after perfusion of the organ with 2.5, 5.0, 7.5, and 10 mM sodium ricinoleate. Colons perfused with control buffer showed the expected normal appearances, whereas ricinoleate produced desquamation of surface epithelial cells. Surface changes in the colon were comparable with those reported after similar treatment of the rabbit ileum. Concomitant with these histological changes was loss of DNA into the lumen of the colon. Dose-related changes in net fluid transport and mucosal permeability (as assessed by lumen to plasma flux of low molecular weight polyethylene glycols and plasma to lumen flux of urea and creatinine) were also associated with ricinoleate perfusion. These structural and functional alterations may contribute to intraluminal accumulation of fluid and catharsis that can result from administration of ricinoleic acid (castor oil). The findings might also pertain to the pathophysiology of steatorrheal diseases, because dietary fatty acids of similar chemical structure are known to have comparable effects on the intestinal mucosa.

Animals↗

Measurements of intestinal permeability using low molecular weight polyethylene glycols (PEG 400). I. Chemical analysis and biological properties of PEG 400.

A new approach to the measurement of intestinal permeability in man has been developed, using low molecular weight polyethylene glycol (PEG 400) as probe molecules. PEG 400 (range of molecular weight 232 to 594) is a mixture of water-soluble molecules of different sizes which can be extracted readily from biological fluids and analyzed by gas-liquid chromatography. PEG 400 is nontoxic, not degraded by intestinal bacteria, not metabolized after absorption, and rapidly excreted in urine. The different-sized molecular components cross the intestinal epithelium at different rates, allowing characterization of the passive permeability properties of the mucosa.

Animals↗