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Biomedical subjects

R E Barry

Publications and source records attributed to R E Barry.

At least 37 records · Page 2Linked to original sources

Acetaldehyde alone may initiate hepatocellular damage in acute alcoholic liver disease.

Acetaldehyde may be the injurious agent in acute alcoholic liver disease. It has been suggested that the mechanism of liver injury in this situation may be immunologically mediated. In the present study acetaldehyde has been bound to human liver plasma membranes. The activation of C3 by the acetaldehyde/membrane product was measured by immunofixation of the separated C3 components. Activation of C3 by acetaldehyde exposed liver plasma membranes was increased to 16.4% compared with 6% by non-exposed membranes (p = 0.004). Human liver plasma membranes bound 212 +/- 18 nmol acetaldehyde per mg membrane protein. The binding constant was 439 +/- 81 microM. It is concluded that acetaldehyde bound to human liver plasma membranes activates the complement sequence and this may be the initial stage in the pathogenesis of acute alcoholic liver disease.

Acetaldehyde↗

Studies on the pharmacokinetics of fluorescein and its dilaurate ester under the conditions of the fluorescein dilaurate test.

Some aspects of the pharmacokinetics of fluorescein have been studied under the conditions of the fluorescein dilaurate test (Pancreolauryl-Test) in healthy volunteers. Dependence of fluorescein excretion on urine volume was investigated in a retrospective study in 370 patients. For intravenously administered fluorescein mean Cmax was 10.9 micrograms/ml with a mean elimination half-life of 286 min. For orally administered fluorescein sodium mean Cmax was 3.5 micrograms/ml with a tmax of 120 min and a t 1/2 of 267 min. Bioavailability of fluorescein by oral administration was 99%. By contrast, fluorescein from fluorescein dilaurate showed a 56% bioavailability under the conditions of the test with a Cmax of 1.8 micrograms/ml, a tmax of 270 min and a tt 1/2 of 246 min. Following enteral absorption of fluorescein hepatic extraction and enterohepatic circulation via the bile occurs, but although the concentrations of fluorescein in the bile may exceed those in the urine the absolute amount is likely to be small. In spite of the enterohepatic circulation fluorescein cleared from the urine within 24 h indicating that no delay between Part 1 and Part 2 of the test seems necessary. However, an adequate urine flow must be maintained throughout the test since a renal clearance/urine flow relationship exists, with fluorescein excretion being increased with increasing urine volume.

Administration, Oral↗

Acetaldehyde binds to liver cell membranes without affecting membrane function.

Acetaldehyde is a major metabolic product of ethanol and is found in high concentrations in the serum during alcohol abuse. The effects of acetaldehyde on isolated rat liver cells and on purified hepatocyte plasma membrane vesicles have been studied. In concentrations of 0-10 millimolar acetaldehyde has been shown to have no detectable effect on either hepatocyte metabolism or gross membrane function and is therefore unlikely to act as a direct metabolic poison. Acetaldehyde, however, is shown to bind to hepatocyte membranes via intermediary Schiff's base formation. The adduction of acetaldehyde to liver cell plasma membranes may have an effect on membrane structure. These findings are consistent with the hypothesis that any injurious effect of acetaldehyde on the liver may be mediated via the immune system rather than being a direct effect on cell metabolism.

Acetaldehyde↗

Twice-daily cimetidine does not increase gastric bacterial flora.

Thirty patients with peptic ulcer (20 duodenal, 10 gastric) underwent glucose-hydrogen (H2) breath tests before and after 6 weeks treatment with cimetidine, 400 mg twice daily. For the group as a whole, basal breath H2 and integrated H2 output over a 2.5 hr test period was unchanged by cimetidine treatment. We conclude that there was no evidence of significant gastric bacterial colonization following twice daily cimetidine treatment.

Adult↗

The pathogenesis of hepatitis in alcohol abuse and jejunoileal bypass.

Acetaldehyde, produced in excessive amounts in alcohol abuse or after jejunoileal bypass, binds to hepatocyte plasma membranes by way of formation of an intermediate Schiff's base. This binding has no effect on cellular metabolism or membrane function but causes physical changes in membrane properties which activate the complement cascade and this results in hepatocellular damage.

Acetaldehyde↗

Fluorescein dilaurate--tubeless test for pancreatic exocrine failure.

The usefulness of fluorescein dilaurate as an indicator of pancreatic exocrine failure has been assessed in 70 patients and normal volunteers. The test consisted of a comparison of urinary fluorescein excretion after ingestion of fluorescein dilaurate with that after ingestion of unesterified fluorescein. The test was easy to perform and acceptable to the patients. The sensitivity of the test was 95%. There was a false-positive rate of 11% in a group of patients who had steatorrhoea which was non-pancreatic in origin. The test can be a useful screening test for the exclusion of pancreatic exocrine failure as a cause of steatorrhoea and can be conducted in outpatients.

Celiac Disease↗

Bioassay of cholecystokinin.

An in vitro bioassay for cholecystokinin which is superior to the previously described in vivo assays has been properly validated mathematically. The specificity of the assay has been assessed by measuring the potency of other polypeptides which share the same C-terminal pentapeptide sequence with cholecystokinin (gastrin, caerulin, octapeptide of cholecystokinin, and pentagastrin). The assay is shown to be quite specific for cholecystokinin. Secretin does not interfere with the assay. Comparison of the relative potency of the two commercially available preparations of cholecystokinin indicates that the two major units of measurement are almost identical in cholecystokinetic potency. One Crick Harper Raper unit of cholecystokinin (Boots) is equivalent to 1.22 +/- 0.12 Ivy dog units of cholecystokinin (Karolinska Institute). The lower limit of sensitivity for the assay was 2.5m IDU/ml.

Biological Assay↗

Gluten-induced mucosal changes in subjects without overt small-bowel disease.

Five normal volunteers, six normal first degree relatives of coeliac patients, and four patients with altered immunity (two primary biliary cirrhosis, one common variable immune deficiency, one immunoglobulin A deficiency) were studied both before and after a six week period during which their normal diet was supplemented by 40 g of gluten per day. Administration of the high gluten diet produced significant architectural changes in the jejunal mucosa of both the normal relatives of coeliac patients and the patients with altered immunity (p less than 0.01). In some cases changes amounted to severe partial villous atrophy. A significant increase in intraepithelial lymphocytes was also observed in the normal relatives of coeliac patients and in the normal volunteers (p less than 0.05); patients with altered immunity had high intraepithelial lymphocyte counts both before and after the high gluten diet. A significant decrease in xylose absorption occurred in the relatives of coeliac patients and in the normal volunteers (p less than 0.05). Two normal relatives and one patient with altered immunity had diarrhoea, which ceased on return to a normal diet. These findings indicate that excessive gluten intake can induce changes in the jejunal mucosal architecture in susceptible individuals who do not have overt coeliac disease.

Adolescent↗

Serum lysozyme activity in coeliac disease: a possible aid to athe diagnosis of malignant change.

Serum lysozyme activities were measured in 34 control subjects, 13 untreated adult coeliac patients, 21 adult coeliac patients on gluten-free diet, and eight coeliac patients with a histiocytic lymphoma. Serum lysozyme activities were raised in three untreated patients, three patients treated with a gluten-free diet, and in only two patients with coeliac disease and lymphoma. Serum lysozyme estimations cannot be recommended as an aid to the diagnosis of lymphoma in patients with coeliac disease.

Adult↗

Physician's use of laparoscopy.

The role of laparoscopy in medical practice was assessed by studying 238 consecutive laparoscopies performed under local anaesthesia by physicians in a single teaching hospital. Indications for laparoscopy were assessment of possible and known hepatic disease, possible disseminated abdominal malignancy, abdominal mass, and conditions such as ascites and splenomegaly. A definitive diagnosis was reached in 223 cases (76.5%). No organic disease was detected in 41 patients, though findings were false-negative in two of them (0.8%). The procedure failed in 15 (6.3%), mostly because adhesions from previous surgery hindered adequate visualisation. Six patients (2.5%) had complications, one of whom subsequently died. If patients are appropriately selected laparoscopy is relatively free of postoperative complications, and is an effective diagnostic procedure in abdominal malignancy and decompensated liver disease. Cost-effectiveness is an additional advantage.

Abdominal Neoplasms↗

Some problems with antacids.

The author points out that because a high intake of Vitamin D and calcium is normally encouraged in pregnancy, care should be taken in the prescription of certain antacids likely to cause alkalosis. Calcium-containing antacids are probably best avoided because of nocturnal acid rebound. Because of undesirable fluid retention in some situations in pregnancy caution should be exercised in the use of sodium-containing antacids. The very high sodium content of some antacids is stressed.

Alkalosis↗

Intestinal adaptation after jejunoileal bypass in man.

Gastrointestinal anatomy and function has been studied prospectively in 12 patients undergoing jejunoileal bypass surgery in order to investigate the adaptive response of the intestinal mucosa. The total thickness of the jejunal mucosa did not change after surgery, but the crypts became relatively deeper, suggesting a more rapid turnover of gastrointestinal cells. The absorption of oxalate was depressed in the immediate postoperative period but had improved toward preoperative levels by 6 months. Vitamin B12 absorption also declined postoperatively, and increased thereafter in the patients with an end-to-end jejunoileostomy, but showed a much smaller recovery in the group with an end-to-side anastomosis. The cholesterol concentration (lithogenicity) of the duodenal bile rose by 30% in the first 3 weeks after surgery, but had returned to preoperative levels by 6 months. The segmental absorption of glucose across the jejunum declined after surgery. Caloric intake also declined, whether measured as the quantity of food that patients elected to eat over a 24-hr period, or as the quantity of a liquid lunch which they consumed over a 20-min period. The level of basal gastric acid was increased postoperatively but the maximal output after histamine stimulation was not. The gastrin response to a standard liquid meal was also significantly increased after surgery. Enteroglucagon secretion showed an increase in 3 weeks and a further increase by 6 months after intestinal bypass surgery. The significance of these changes to intestinal adaptations is discussed.

Bile Acids and Salts↗

Role of intestinal microflora in colonic pseudoobstruction complicating jejunoileal bypass.

A double-blind crossover study using placebo and antibiotics effective against either aerobic or anaerobic organisms has been performed to elucidate the role of intestinal microflora in the pathogenesis of colonic pseudo-obstruction, which is now established as an important complication of jejunoileal bypass. Using strict Virginia Polytechnic Institute (VPI) technique, quantitative bacterial studies of the intestinal flora in the region of bypassed bowel have been correlated with symptoms of abdominal pain and distension. It has been shown that antibiotics effective against obligate anaerobes rapidly relieve the symptoms of pseudo-obstruction and this coincides with the disappearance of these organisms from this region of bowel. Symptoms rapidly recur when anaerobic organisms repopulate the bowel. It is concluded that obligate anaerobes may play a role in the pathogenesis of this complication.

Bacteria↗

Lipid composition of bile in morbid obesity before and after jejunoileal bypass surgery.

Bile cholesterol, phospholipids, total bile acids, individual bile acids, and fatty acid compositions of bile neutral lipids and phospholipids were analyzed before, at one month and at six months following jejunoileal bypass surgery in a series of morbidly obese patients. Preoperative mole percentages of cholesterol and lithogenic indices were high, indicating that biles were supersaturated with cholesterol and outside the micellar solubility zone when plotted on triangular coordinates. At the one month post-operative period percentages of cholesterol and lithogenic indices were significantly increased as compared to the pre-operative state. At six months post-operatively these values had decreased to approximately the pre-operative levels. No changes were observed in percentages of lithocholic acid, but deoxycholic acid decreased to markedly low levels at one month and remained low at the six month post-operative interval. Relative proportions of cholic acid increased, and the ratio of cholic to chenodeoxycholic acid was significantly increased at both post-operative intervals. No significant changes were noted in bile neutral lipid or phospholipid fatty acid composition, indicating that no depletion of essential fatty acids had occurred.

Adult↗