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Biomedical subjects

B J Rathbone

Publications and source records attributed to B J Rathbone.

At least 37 records · Page 2Linked to original sources

Monocyte zinc and in vitro prostaglandin E2 and interleukin-1 beta production by cultured peripheral blood monocytes in patients with Crohn's disease.

This study investigated the relationship between zinc status and prostaglandin E2 and interleukin-1 beta production by cultured monocytes in patients with Crohn's disease. Monocyte zinc was significantly decreased in both 12 inpatients and 22 outpatients compared with controls (P less than 0.001) but lymphocyte and polymorphonuclear cell zinc were normal. When cultured monocytes from 10 outpatients with Crohn's disease were stimulated with lipopolysaccharide, prostaglandin E2 production increased markedly, coupled with a fall in monocyte zinc. In matched controls, prostaglandin E2 production was significantly less and monocyte zinc remained stable. No difference in interleukin-1 release was noted between patients and controls. The addition of prednisolone to cell cultures suppressed prostaglandin E2, interleukin-1 synthesis, and monocyte zinc did not change. Zinc chloride augmented prostaglandin E2 production in patients, but not controls, and interleukin-1 remained stable. These results demonstrate a link between low monocyte zinc concentration and excessive prostaglandin production in patients with Crohn's disease.

Cells, Cultured↗

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↗

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↗

Acute Helicobacter pylori infection: clinical features, local and systemic immune response, gastric mucosal histology, and gastric juice ascorbic acid concentrations.

The symptomatology of a case of acute infection with Helicobacter pylori is described, together with the accompanying changes in gastric mucosal histology, local and systemic humoral immune response, and gastric ascorbic acid concentration. The patient was an endoscopist, previously negative for the carbon-14 urea breath test, who had a week of epigastric pain and then became asymptomatic. H pylori was detected by culture of antral biopsy specimens and was still present after 74 days. Five days after infection the histological findings showed acute neutrophilic gastritis; by day 74 changes of chronic gastritis were evident. The patient seroconverted by IgG enzyme linked immunosorbent assay by day 74, but a mucosal IgM and IgA response was evident as early as day 14. Infection was accompanied by a transient hypochlorhydria but a sustained fall in gastric juice ascorbic acid concentration.

Acute Disease↗

Non-steroidal anti-inflammatory drugs, hiatus hernia, and Helicobacter pylori, in patients with oesophageal ulceration.

The frequency of oesophageal ulceration in 55 patients undergoing endoscopy for dyspeptic symptoms and who had recently used NSAIDs was studied, and compared with 86 patients seen in the same clinic who had not recently used these drugs. Oesophageal ulceration was significantly more common in those who had used NSAIDs (P = 0.012), and also showed a highly significant association with the presence of a hiatus hernia (P less than 0.001). No association was found between the presence of gastric Helicobacter pylori and either oesophageal ulceration or histological oesophagitis. Patients receiving NSAIDs, especially those with a hiatus hernia, are at risk of oesophageal ulceration and presumably subsequent stricture formation. This should be borne in mind when prescribing these agents.

Adult↗

Helicobacter pylori associated chronic gastritis and peptic ulceration in patients taking non-steroidal anti-inflammatory drugs.

Helicobacter pylori is now recognized as a frequent cause of histological chronic gastritis, and this has radically changed our understanding of this common condition. In the light of these developments, the traditional view that non-steroidal anti-inflammatory drugs are one of the common 'environmental' causes of chronic gastritis has been re-examined. Gastric mucosal biopsies have been studied from 430 patients undergoing routine upper gastrointestinal endoscopy, 99 of whom had recently been taking non-steroidal anti-inflammatory drugs. No significant association was found between the use of these drugs and either the presence of chronic gastritis or the frequency of colonization with H. pylori, although there was a strong association (P less than 0.0001) between H. pylori and gastritis. Non-steroidal anti-inflammatory drugs appear, however, to modify the inflammatory process in the gastric body, leading to a lower frequency of atrophic gastritis (P less than 0.05). The majority of peptic ulcers were associated with H. pylori irrespective of non-steroidal anti-inflammatory drug use, but there was a higher frequency of H. pylori negative ulceration in the patients who had used these agents (P less than 0.04). Peptic ulceration was uncommon in the absence of either H. pylori or recent non-steroidal anti-inflammatory drug use.

Adolescent↗

Bacterial adhesion and disease activity in Helicobacter associated chronic gastritis.

Ultrastructural examination of biopsies showing Helicobacter pylori associated chronic gastritis reveals close attachment between gastric surface epithelial cells and the organism. The finding of 'adhesion pedestals', which represents a cellular response to the presence of the organism, is analogous to the response of intestinal cells to enteropathogenic E coli. Thus the development of bacterial attachment sites in H pylori associated gastritis might be an indication of pathogenicity. We have therefore explored the relationship between the proportion of organisms forming attachment sites and histological indices of disease 'activity'. Antral biopsies from 40 patients with H pylori positive gastritis were examined histologically and ultrastructurally, and the percentage of attached organisms compared with subjective assessments of epithelial degeneration, mucin depletion, polymorphonuclear and chronic inflammatory cell infiltration. We found a significant increase in the proportion of attached bacteria in cases showing histological epithelial degeneration, and a significant decrease in cases showing intraepithelial polymorph infiltration. The direct relationship between bacterial attachment and cellular degeneration lends further support to a pathogenic effect. Reduced attachment in the face of polymorph infiltration might indirectly reflect aspects of the immune response--namely, blocking of adhesion by IgA, with complement activation and generation of leucotactic factors.

Bacterial Adhesion↗

Gastric epithelium in the duodenum: its association with Helicobacter pylori and inflammation.

Duodenal biopsy specimens from 471 adults and 47 children were examined to determine the prevalence and distribution of gastric epithelium in the duodenal bulb in relation to age, gender, gastroduodenal inflammation, smoking, alcohol and consumption of nonsteroidal anti-inflammatory drugs (NSAID). Gastric metaplasia was present in the anterior wall duodenal biopsy specimen in 31%, was significantly less common in patients under 17 than in adults, and was more common in males than females. In sixty two adults who underwent multiple radial duodenal biopsy gastric metaplasia was randomly distributed around the duodenal circumference; sixty three per cent of the patients with gastric metaplasia found on multiple biopsy were detected by just the anterior biopsy. Gastric metaplasia was not obviously associated with alcohol, cigarette, or NSAID consumption. While the presence of gastric metaplasia was associated with adulthood, male sex, and low fasting gastric juice pH, its extent was associated with active duodenitis and Helicobacter-associated gastritis. On logistic regression, gastric metaplasia in the duodenum and gastric Helicobacter pylori were independent predictors of active duodenitis, but were not significantly associated with inactive duodenal inflammation. H pylori was observed in duodenal biopsy specimens from 32 patients, all with active duodenitis; bacteria were present only on foci of gastric metaplasia, and were more likely to be seen when the metaplasia was extensive. It is proposed that inflammatory injury to the duodenal mucosa by H pylori may stimulate the development of further gastric metaplasia, and that the area of duodenum susceptible to colonisation with H pylori may therefore increase progressively until mucosal integrity is compromised and ulceration supervenes.

Adolescent↗

Comparison of ELISA antigen preparations alone or in combination for serodiagnosing Helicobacter pylori infections.

The immunoglobulin G antibody response to Helicobacter pylori was assessed in 78 patients with non-ulcer dyspepsia using five different antigen preparations. All patients were endoscoped and biopsied. The H pylori state was determined histologically on at least two endoscopic biopsy specimens using a modified Giemsa stain. The ultracentrifuged cell sonicate, acid glycine extract, and 120 kilodalton protein antigens were specific in diagnosing infection (95-98%), but had only moderate sensitivity (70-84%). By mixing either of the two complex antigens with the 120 kilodalton protein, the sensitivity of the test was increased to 97% without affecting the high specificity. The combination of ultracentrifuged sonicate or acid glycine extract with the 120 kilodalton protein therefore seems to be superior to the individual antigen preparations and is particularly suitable for the serodiagnosis of H pylori infection.

Antibodies, Bacterial↗

Clinical significance of the immunometric measurements of hyaluronic acid.

Hyaluronic acid (HA), an unbranched high molecular weight polysaccharide can now be measured by several immunometric assays. The connective tissues are the main source of HA and it is destroyed mainly in the liver. Very high levels of HA occur in mesothelioma. Wilms' tumour and acute liver failure, and moderate increases in rheumatoid diseases, renal failure and cirrhosis. Local increased production of HA is a feature of several forms of lung disease. HA is an indicator of connective tissue turnover, of the function of the receptor mechanisms for its capture and destruction by the liver, and of the removal of low molecular weight fragments by the kidney.

Arthritis, Rheumatoid↗

Ascorbic acid: a factor concentrated in human gastric juice.

1. Concentrations of ascorbic acid (ascorbic and dehydro-ascorbic; A + D; measured by the 2,4-dinitrophenylhydrazine method) of nearly three times those of plasma are present in gastric juice samples from patients with normal gastric histology. 2. A significant reduction in gastric juice ascorbic acid (A + D) was observed in patients with chronic gastritis. This reduction in concentration was independent of the grade of gastritis. 3. Concentrations of ascorbic acid (A + D) in gastric biopsy specimens were consistently higher in the antrum than in the body of the stomach. 4. These data demonstrate that considerable quantities of ascorbic acid (A + D) are normally 'secreted' into the stomach. 5. Ascorbic acid (ascorbic only; A; measured by h.p.l.c.) was present predominantly in its biologically active form in the patients with normal gastric histology. However, in patients with gastritis, independent of grade, ascorbic acid was present predominantly in its oxidized, biologically inactive form.

Adult↗

The role of serology in the diagnosis of Campylobacter pylori infection.

Circulating antibodies to Campylobacter pylori in patients with campylobacter-associated gastritis are sufficiently specific to allow serodiagnosis of this condition. This is possible by various techniques, the most convenient being enzyme-linked immunosorbent assay. Applications of serodiagnosis are in two areas--in clinical practice, where proper evaluation is still required, and in epidemiology. Here serodiagnosis shows the prevalence of C. pylori in the general population and in specific population groups. A study of C. pylori and dyspeptic symptoms in a group of healthy blood donors showed a significant association between C. pylori and history of peptic ulceration. However in most donors the gastritis was clinically silent.

Adult↗

Lymphocytic gastritis--relationship to Campylobacter pylori infection.

The existence of a distinctive form of chronic gastritis characterized by marked infiltration of the surface and pitlining epithelium by mature T lymphocytes has been confirmed. Seventeen cases were identified amongst 382 patients with active chronic gastritis (4.5 per cent). The cases with lymphocytic gastritis had significantly higher counts of intraepithelial lymphocytes than sex and age-matched controls drawn from a series of patients with the usual form of active Type B chronic gastritis. Furthermore, the lymphocytic gastritis group exhibited unusual endoscopic findings, namely erosions and 'raised lesions', in the body of the stomach. Such appearances have been previously described as 'varioliform' gastritis. Only seven of the patients (41 per cent) had C. pylori-positive biopsies, compared with over 90 per cent in the generality of active chronic gastritis, but all but two of the eleven cases tested had serological evidence of C. pylori infection. While the pathogenesis of this condition is unclear, the histological resemblance to coeliac disease suggests that lymphocytic gastritis might also represent an abnormal response to a local antigen to which the patient has become sensitized. It is possible that this antigen is C. pylori.

Adult↗

The characterization and pathological significance of gastric Campylobacter-like organisms in the ferret: a model for chronic gastritis?

Gastric campylobacter-like organisms (CLO) were isolated from gastric tissues removed at sacrifice from 17 mature ferrets; all animals were colonized, but no macroscopic mucosal lesions or histological features of chronic gastritis were seen. The isolates resembled Campylobacter pylori in many cultural and biochemical characteristics, and produced substantial urease activity, but there were sufficient differences from C. pylori to suggest that ferret gastric CLO represents a separate species. Comparison of human C. pylori and ferret gastric CLO may help to elucidate the pathogenicity of the former in patients with gastritis, and the ferret may serve as a useful animal model for the study of C. pylori infection.

Animals↗