Search PubMedSearch

Biomedical subjects

M S Losowsky

Publications and source records attributed to M S Losowsky.

At least 19 recordsLinked to original sources

Helicobacter pylori serology in patients with coeliac disease and dermatitis herpetiformis.

AIMS: To investigate whether Helicobacter pylori infection or autoimmune gastritis is responsible for the reported increase in gastric pathology and abnormalities of gastric function in patients with coeliac disease and dermatitis herpetiformis (DH). METHODS: Serum H pylori IgG antibodies were assayed by enzyme linked immunosorbent assay and intrinsic factor antibodies by radioimmunoassay in 99 patients with coeliac disease and 58 patients with dermatitis herpetiformis from two geographic areas. RESULTS: H pylori positivity in patients with coeliac disease and dermatitis herpetiformis increased with age, reaching 50% and 70%, respectively, in patients over 50 years. The percentage H pylori seropositivity in coeliac disease did not differ from the percentage positivity observed in 250 similarly aged blood donors from the same geographic area (Leeds). Seropositivity in patients with dermatitis herpetiformis was not significantly different from the level of positivity observed in 98 age matched patients without dermatitis herpetiformis attending the same Edinburgh dermatology clinic. Only one patient with coeliac disease had positive intrinsic factor antibodies. H pylori seropositivity in Edinburgh control subjects under 30 years of age (41.9%) was significantly higher (p less than 0.03) than in Leeds controls (18%) of corresponding age. An increasing prevalence of H pylori seropositivity with age in coeliac disease and dermatitis herpetiformis paralleled that of the control groups. CONCLUSIONS: Gastritis in coeliac disease and dermatitis herpetiformis is largely caused by H pylori infection at a level that is no different from that of the general population. Any increase in the prevalence of gastritis in these two diseases might be caused by lymphocytic gastritis rather than pernicious anaemia.

Adolescent

Gamma delta T cell receptor-positive cells of the human gastrointestinal mucosa: occurrence and V region gene expression in Heliobacter pylori-associated gastritis, coeliac disease and inflammatory bowel disease.

T cells expressing the gamma delta heterodimer of the T cell receptor (TCR) were studied with respect to their occurrence and expression of gamma delta TCR variable region (V) genes in the normal gastrointestinal mucosa and in a variety of inflammatory conditions. In controls, gamma delta TCR+ cells were a minority population confined to the epithelial compartment of stomach, small bowel and colonic mucosae. Unlike in the periphery, gastro-intestinal gamma delta TCR+ intraepithelial lymphocytes (IEL) were mainly V delta 1+ (89.98 +/- 17.70%); few were V delta 2+ (6.04 +/- 13.8%) or V gamma 9+ (11.38 +/- 10.73%). All gamma delta TCR+ IEL were CD5low; nearly half were CD8+ and the remainder were CD4-CD8- 'double negatives'. There was no significant change from normal in percentages of gamma delta TCR+ IEL in H. pylori-associated gastritis, Crohn's disease and ulcerative colitis. However, in coeliac disease, gamma delta TCR+ IEL were elevated from 2.54% (+/- 1.71) in controls to 29.6% (+/- 16.1) in untreated patients (P less than 0.001) and 18.5% (+/- 7.2) in treated patients (P less than 0.001) and more were CD4-CD8-. Otherwise, gamma delta TCR+ IEL phenotypes were little changed: the majority remained V delta 1+V delta 2-V gamma 9- and all were CD5low. These data suggest that increased gamma delta TCR+ IEL are not a generalized response to intestinal inflammation or to stress proteins, although the typical V delta 1+V delta 2-V gamma 9- CD5low phenotype is retained.

Adult

The effect of wheat bran and pectin on paracetamol absorption in the rat.

1. The absorption of an oral dose of paracetamol was measured in rats given either a basal fibre-free diet, or the basal diet with either pectin or bran added. 2. Urinary excretion of the oral dose was significantly greater during the first 8 h in the pectin-fed rats compared with those on basal diet, though cumulative excretion after 72 h was the same. 3. Free paracetamol levels in the plasma were significantly higher in the pectin-fed rats compared with those on basal diet at 30, 60, 90 and 120 min after the oral dose. 4. The plasma half-life of intravenously-injected paracetamol was shorter in the pectin-fed rats than in those on basal diet alone, but the antipyrine half-lives were not significantly different. 5. Pectin feeding had no effect on either the apparent volume of distribution of paracetamol and antipyrine, or on the rate of gastric empyting. 6. Perfusion of the whole length of the small bowel showed a significantly greater capacity for paracetamol absorption in the pectin-fed rats. 7. Bran had no effect on paracetamol absorption. 8. It was concluded that dietary fibre intake affects drug absorption and that the effect varies with the type of fibre. Unexpectedly pectin accelerates rather than retards absorption of paracetamol, though the mechansim of this effect is unknown.

Acetaminophen

The effect of pectin on the structure and function of the rat small intestine.

1. The effect of pectin on the structure and function of the rat small intestine was compared with that of a standard pellet diet and of a fibre-free basal diet. 2. The length and wet weight of the small bowel was significantly greater inpect in-fed rats than in either pellet- or basal-diet-fed rats. 3. Histological measurements of longitudinal sections from the small bowel showed a significantly greater crypt depth and muscle layer thickness in the mid-jejunum and ileum of the pectin fed rats. Villous height showed less variation. 4. The specific activity of alkaline phosphatase (EC 3.1.3.1) and leucyl-beta-naphthylamidase (EC 3.4.11.1) in mucosal scrapings was significantly lower in the upper jejunum of pectin-fed rats compared with either of the other dietary groups. The differences were not so marked in mid-jejunum or ileum. 5. Glucose absorption measured in vivo from jejunal and ileal loops was similar in all three dietary groups. 6. With two minor exceptions there were no significant differences in any of these measurements between the pellet- and basal-diet-fed rats. 7. These findings could be explained by increased epithelial cell turnover caused by pectin. The possible mechanisms of this are discussed. 8. The effect of pectin on the human small bowel requires study before it can be widely prescribed in man.

Alkaline Phosphatase

The gastrointestinal absorption of paracetamol in the rat.

The absorption of [3H]paracetamol by rat small intestine, colon and stomach was studied in vivo and in vitro. Small intestinal in vivo studies, using a wide range of drug concentrations, showed that absorption was efficient and uniform throughout the small bowel, no site showing preferential absorption. Double reciprocal and direct plots indicated first order kinetics. The pattern was not observed when uptake was occurring from high concentrations of paracetamol in suspension. Gastric and colonic in vivo studies showed that there was appreciable absorption of [3H]paracetamol from these sites. In vitro studies using everted intestinal sacs showed no effect on paracetamol transfer when the incubation temperature was lowered to 10 degrees C or when iodoacetate (5 X 10(-2)M) and 2.4 dinitrophenol (5 X 10(-4)M) was added to the incubation medium. There was, however, a significant reduction in transfer of paracetamol against a concentration gradient of 10:1 applied across the mucosa. These data suggest that the uptake of paracetamol is by a passive transport process and confirm the efficiency of paracetamol absorption observed indirectly by others.

Acetaminophen

Clinical relevance of an unfused pancreatic duct system.

In man, the main pancreatic duct is normally derived from ventral and dorsal embryological buds of the pancreas. In a minority of people, failure of fusion of the two buds results in separate drainage of the dorsal and ventral pancreas, so that the accessory duct provides the main drainage for the gland. Patients with this anomaly demonstrated at endoscopic retrograde pancreatography (ERP) have been investigated to assess whether non-fusion of the main pancreatic duct predisposes to the development of pancreatitis. A failure of fusion of the pancreatic ducts was seen in 21 out of 449 (4.7%) successful pancreatograms; four of these 21 patients had definite clinical evidence of pancreatitis and two patients had possible pancreatic disease, but in the remainder the anomaly was not considered to be clinically relevant. An abnormal pancreatogram suggesting pancreatitis was present in 116 out of the 428 patients (27.1%) with a normally fused duct system. The anomaly was found as frequently in the whole series as it was seen in patients with pancreatitis. These findings suggest that embryological failure of pancreatic duct fusion does not predispose to the development of pancreatitis. However, the presence of this anomaly may lead to misinterpretation of ultrasonographic and CT scan findings.

Adolescent

Hypobetalipoproteinaemia--a variant of the Bassen-Kornzweig syndrome.

A patient is reported with hypobetalipoproteinaemia and clinical features resembling the Bassen-Kornzweig syndrome (abetalipoproteinaemia) more completely than previously described. This supports a link between hypobetalipoproteinaemia and abetalipoproteinaemia and it is suggested that the Bassen-Kornzweig syndrome has a wide spectrum with serum betalipoprotein ranging from absent to normal. It is likely that there are different genetic entities with similar end results.

Abetalipoproteinemia

Radio-opaque pellets as faecal markers for faecal fat estimation in malabsorption.

Thirty-seven patients undergoing routine investigation for malabsorption were given radio-opaque pellets (ROP) which were compared with polyethylene glycol and chromic oxide as continuous faecal markers. Percentage recovery of all markers showed a wide range. The recovery of all markers was very similar, and radio-opaque pellet-corrected daily faecal fat correlated very closely with PEG-and chromic oxide-corrected fat results. Estimation of ROP is precise, simple, and minimises faecal handling. ROP are suitable for routine use in faecal fat studies and have advantages over markers used at present.

Chromium

Hypocalcaemic chorea secondary to malabsorption.

A patient presented with chorea and a recent history of Crohn's disease. Investigation revealed the cause of the chorea to be hypocalcaemia secondary to malabsorption. So far as is known there has been no previous report of hypocalcaemic chorea due to malabsorption.

Chorea

Radiation pancreatitis: a clinical entity?

2 cases of pancreatic disease in patients with malabsorption following small bowel radiation injury are reported. It is suggested that the pancreatic disease present in these patients occurred as a result of previous radiotherapy.

Humans

Improved diagnostic accuracy of a modified oral pancreatic function test.

The oral pancreatic function test (PFT) depends upon urinary recovery of p-aminobenzoic acid (PABA) released by chymotrypsin hydrolysis of orally administered N-benzoyl-L-tyrosyl-p-aminobenzoid acid. The diagnostic value of the test is limited because falsely abnormal results frequently occur in patients with bowel or liver disease in whom PABA recovery is impaired by abnormal absorption or hepatic conjugation, even though pancreatic function is normal. To overcome this problem, we have modified the oral PFT to correct for impaired PABA absorption and conjugation. Results of the oral PFT have been compared with urinary recovery of an equivalent dose of free PABA in order to derive a PABA excretion index (PEI). When the modified oral PFT is used, the PEI clearly distinguished patients with pancreatic disease from normal subjects. In patients with small-bowel or liver disease and normal exocrine pancreatic function, the PEI results were similar to those of normal subjects, although a previous oral PFT had been falsey abnormal. The modified test can therefore distinguish abnormal results due to pancreatic disease from the falsely abnormal results found in liver and small-bowel disease.

4-Aminobenzoic Acid