PubMed Health⌕ Search

Biomedical subjects

M S Losowsky

Publications and source records attributed to M S Losowsky.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1991

Improved bioavailability from a spironolactone beta-cyclodextrin complex.

The relative bioavailabilty of spironolactone from a complex with beta-cyclodextrin has been evaluated. Capsules containing 100 mg micronised spironolactone powder were compared with 100 mg spironolactone beta-cyclodextrin complex in 8 healthy volunteers by a single dose, double blind, crossover pharmacokinetic study. Subjects were randomly allocated to each preparation and crossed over after 2 weeks. Relative bioavailability was assessed by the measurement of serum canrenone concentrations. The mean relative bioavailability of the spironolactone cyclodextrin complex, compared to the micronised spironolactone powder, was 233%. Statistical analysis (Wilcoxon signed rank test) revealed that this difference was significant with a mean area under the serum concentration time curve of 3.90 and 1.88 mg.h.l-1 for the complex and micronised spironolactone powder, respectively. Four of the volunteer also received a 100 mg spironolactone tablet (Aldactone) under identical conditions. Pharmacokinetic analysis revealed that the mean relative bioavailability of the spironolactone beta cyclodextrin complex and micronised powder when compared with spironolactone tablets (Aldactone) was 252% and 124%, respectively. There was no change in the canrenone elimination half lives of each subject.

Adult↗
PubMed1991

Mucosal humoral immune response to Helicobacter pylori in patients with duodenitis.

The humoral immune response to Helicobacter pylori infection in the duodenum has been investigated by short-term in vitro culture, ELISA, and immunoblotting techniques. H. pylori IgA secretion by duodenal bulb biopsies was significantly increased (P less than 0.001) in patients with duodenitis. The IgA response to H. pylori in patients with duodenitis was restricted to the first part of the duodenum; second part duodenal biopsies secreting significantly (P less than 0.001) less IgA during culture in vitro. H. pylori IgG antibody secretion by cultured biopsies was also significantly increased (P less than 0.01) in patients with duodenitis and those with gastric H. pylori infection but without duodenitis. Immunoblotting of duodenal bulb culture supernatants showed positive recognition by the mucosal IgA response of H. pylori antigens in the region of 120, 90, 61, and 31-26 kDa in patients with duodenitis. Serologically, such patients showed little evidence of IgA H. pylori antibodies by immunoblotting. These results demonstrate that the inflammatory response in the duodenal mucosa of patients with duodenitis represents a specific highly localized humoral response to H. pylori.

Adult↗
PubMed1991

Serum hyaluronate as a marker of hepatic derangement in acute liver damage.

Twenty patients with paracetamol(acetaminophen)-induced acute liver damage of varying severity were studied longitudinally with assessment of clinical state, standard liver function tests and radiometric hyaluronate (HYA) assay (Pharmacia). In patients (n = 6) who developed coma, HYA rose rapidly with clinical deterioration to reach a median value of 27,510 micrograms/l, 7 days post-ingestion, which was significantly higher (p less than 0.005) than in patients (n = 7) who exhibited only marked derangement of liver function tests without evidence of encephalopathy, HYA median value of 3240 micrograms/l. These peak values showed no correlation to the peak values of serum alanine aminotransferase (ALT). A third group of patients (n = 7) who were treated with N-acetyl cysteine, did not exhibit any evidence of liver failure and showed no significant rise in levels of HYA or ALT. The data demonstrate that HYA is a rapidly changing marker of liver derangement which appears to follow the clinical course of the patient. The increase to extremely high levels in patients with hepatic encephalopathy, suggests that there is a reversible defect in the hepatic endothelial cell HYA receptor, possibly due to endothelial cell damage or release of toxins from the necrotic liver.

Acetaminophen↗
PubMed1991

Is persistent adenovirus 12 infection involved in coeliac disease? A search for viral DNA using the polymerase chain reaction.

It has been shown that partial amino acid sequence homology between alpha gliadin and an early region protein (E1B-58 kDa) of adenovirus 12 results in immunological cross reaction. This led to the proposal that prior infection by adenovirus 12 could be associated with the development of coeliac disease. To examine this hypothesis, evidence was sought of persistent adenovirus 12 infection in the small intestinal mucosa of patients with coeliac disease. DNA isolated from biopsy samples from 24 control and 18 coeliac disease patients was analysed by the polymerase chain reaction for adenovirus 12 DNA encoding the E1B-58 kDa protein. Four of 18 coeliac disease and two of 24 control patients were positive. There is thus a low prevalence of this infection on both groups of patients but certainly no significantly increased incidence in coeliac disease. These results suggest that persistent adenovirus 12 infection is not a major element in the pathogenesis of coeliac disease.

Adenoviridae↗
PubMed1991

Plasma beta endorphin in cirrhosis and renal failure.

Whether the plasma concentration of beta endorphin was increased in hepatic cirrhosis like that of smaller opioid peptides methionine enkephalin and leucine enkephalin was determined. Its concentration in chronic renal failure was also measured. Plasma beta endorphin was not significantly raised in cirrhotic patients with or without ascites (medians 5.2 pmol/l and 4.7 pmol/l respectively) compared with disease control subjects (4.9 pmol/l) and healthy control subjects (4.9 pmol/l). In contrast, the peptide was increased 2.5 fold (p less than 0.001) in chronic renal failure (12.4 pmol/l) and was found in many of these patients' urine. The data are compatible with the hypothesis that the liver may play an important role in the elimination of opioid peptides of octapeptide size or less but not the larger peptides such as beta endorphin.

Humans↗
PubMed1991

Septicaemia after colonoscopy in patients with cirrhosis.

Two patients with ulcerative colitis and chronic active hepatitis with cirrhosis, who developed Gram negative septicaemia after colonoscopy are described. These and two similar reported cases indicate that giving prophylactic antibiotics to patients with cirrhosis undergoing colonoscopy should be considered, particularly when the cirrhosis is advanced.

Adult↗
PubMed1991

Hodgkin's disease presenting as liver abscesses.

A patient is reported who presented with sterile hepatic abscesses which proved to be the first manifestation of Hodgkin's disease. He failed to improve with antibiotic treatment but responded to combined chemotherapy. Liver involvement as the first sign of Hodgkin's disease is rare. Liver abscesses due to Hodgkin's disease seem to be previously unreported.

Adult↗
PubMed1991

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↗
PubMed1991

Are patients with primary biliary cirrhosis hypermetabolic? A comparison between patients before and after liver transplantation and controls.

Wasting is common in end-stage primary biliary cirrhosis and causes concern in patients facing liver transplantation. We have quantified resting metabolic rate and diet-induced thermogenesis in seven patients with primary biliary cirrhosis, in seven patients after liver transplantation who had previously been diagnosed as having primary biliary cirrhosis and in seven controls. Resting metabolic rate was elevated in the primary biliary cirrhosis group (4.44 +/- 0.81 kJ/hr/kg body wt; mean +/- S.D.) compared with the post-liver-transplantation group (3.39 +/- 0.40 kJ/hr/kg body wt) (p less than 0.005) and compared with control subjects (3.65 +/- 0.23 kJ/hr/kg body wt) (p less than 0.01). A highly significant relationship was found between the severity of liver disease in the primary biliary cirrhosis group, as assessed by Child-Pugh score, and the resting metabolic rate group (r = 0.93; p less than 0.005). After a liquid meal (41 kJ/kg body wt), the metabolic rate increased, with similar peak changes from baseline occurring in all three groups. However, the rise persisted significantly longer in the primary biliary cirrhosis patients, and thus the integrated mean postprandial energy expenditure over the 4-hr postprandial observation period was greater in the primary biliary cirrhosis group than in the other two groups (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1990

T lymphocyte stimulation of human small intestinal glycoprotein biosynthesis: effects of anti-CD3 antibody on normal and coeliac mucosa.

The effects of mucosal T-cell activation on human small intestinal glycoprotein biosynthesis have been examined during short-term culture in vitro. The incorporation of 3H-glucosamine into tissue and secreted glycoproteins was determined. Activation of mucosal T lymphocytes of normal duodenal biopsies with the monoclonal anti-CD3 antibody significantly increased both the total glucosamine incorporation into glycoproteins (p less than 0.01) and the secretion of in vitro radiolabelled glycoproteins (p less than 0.001). This effect was inhibited by ciclosporin. Secretion of glycoproteins was also stimulated by culture with pokeweed mitogen. In patients with coeliac disease, culture of small intestinal biopsies with anti-CD3 antibody significantly increased (p less than 0.05) glycoprotein biosynthesis in treated patients, but had no stimulatory effect in untreated patients with villous atrophy. These results show that activation of mucosal T lymphocytes induces quantitative changes in intestinal glycoprotein synthesis and secretion and T lymphocytes therefore have an important role in non-specific intestinal defences. The results are consistent with the suggestion that increased glycoprotein synthesis and secretion in untreated coeliac mucosa result from T-cell activation.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1990

The visual evoked potential in clinical hepatic encephalopathy in acute and chronic liver disease.

Flash visual evoked potentials were measured in 19 patients with chronic liver disease and in 19 patients with acute hepatic damage secondary to paracetamol overdose with and without clinical hepatic encephalopathy. The flash visual evoked potential showed a series of changes which correlated with the clinical grade and the delta activity of the electroencephalogram in chronic liver disease, and with the delta activity of the electroencephalogram but not with the clinical grade in acute hepatic damage. The changes observed in the flash visual evoked potential in the encephalopathy of chronic liver disease were different from those seen in the corresponding clinical grade of acute hepatic damage, suggesting different pathogenetic mechanisms for encephalopathy in these two conditions.

Acute Disease↗