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Biomedical subjects

R V Heatley

Publications and source records attributed to R V Heatley.

At least 55 records · Page 3Linked to original sources

The effect of dietary vitamin E deficiency on plasma zinc and copper concentrations.

Vitamin E and zinc have a number of functions in common, including membrane stabilisation, antioxidant function and modulation of prostaglandin metabolism. Previous studies have shown vitamin E malabsorption during zinc depletion and it appears that there is an interaction between the two nutrients. In this study we have investigated whether vitamin E deficiency affects zinc and copper concentrations in experimental animals. Male Wistar rats were maintained on a vitamin E deficient diet for either 6 or 10 months. At the end of the experimental period all animals had undetectable plasma vitamin E levels and increased red cell fragility. Plasma zinc concentrations were significantly reduced in all vitamin E deficient animals compared to control rats (p<0.002) and copper levels were reciprocally elevated (p<0.002). It appears likely that decreased zinc levels may represent redistribution of circulating zinc to tissues and cells as a secondary antioxidant, or for membrane stabilisation or prostaglandin synthesis.

Journal Article↗

Ageing and duodenal mucosal immunity.

The production of immunoglobulins by duodenal mucosa in young and old subjects was studied. For 20 elderly people (mean age 85.3 years) and 18 young subjects (mean age 34.5 years) the amounts of the immunoglobulins IgA, IgG and IgM synthesized and secreted by a duodenal biopsy over a 2-day period were compared. There was no significant difference in the immunoglobulin production between the two groups. This suggests that age itself may have no effect on duodenal mucosal immunity.

Adult↗

The effect of dietary supplementation with vitamins A, C and E on cell-mediated immune function in elderly long-stay patients: a randomized controlled trial.

Thirty elderly long-stay patients were randomly allocated to receive either placebo or dietary supplementation with vitamins A, C and E for 28 days. Nutritional status and cell-mediated immune function were assessed before and after the period of supplementation. Following vitamin supplementation, cell-mediated immune function improved as indicated by a significant increase in the absolute number of T cells (p less than 0.05), T4 subsets (p less than 0.05), T4 to T8 ratio (p less than 0.01) and the proliferation of lymphocytes in response to phytohaemagglutinin (p less than 0.01). In contrast, no significant changes were noted in the immune function of the placebo group. We conclude that supplementation with the dietary antioxidants vitamins A, C and E can improve aspects of cell-mediated immune function in elderly long-stay patients.

Aged↗

Alcohol consumption in patients with colorectal adenomatous polyps.

The risk of developing colorectal adenomatous polyps is probably increased by a variety of dietary and environmental factors. We found an association with current alcohol and cigarette consumption. The risk of polyps was increased three times in drinkers who did not smoke and two times in smokers who did not drink, with those who both drank and smoked having 12 times the risk of total abstainers. Since colonic adenomatous polyps are generally regarded as premalignant lesions, these results lend support to the view that alcohol consumption may be an important factor in the pathogenesis of colorectal neoplasia, thus reinforcing the proposed polyp/carcinoma sequence in colorectal carcinogenesis. The role of smoking, however, is less clear particularly since the lack of association of colorectal carcinoma and smoking has been reported in many other studies.

Aged↗

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↗

Mucosal tumour necrosis factor alpha and interleukin-6 in patients with Helicobacter pylori associated gastritis.

The production of tumour necrosis factor alpha (TNF alpha) and interleukin-6 by human antral mucosa during short term culture in vitro has been measured by enzyme linked immunosorbent assay. TNF alpha and interleukin-6 concentrations in culture supernatants were significantly greater (p less than 0.001) in patients infected with Helicobacter pylori, all of whom had chronic gastritis, than in patients who were H pylori negative with histologically normal gastric mucosa. Among H pylori colonised patients, TNF alpha concentrations were significantly higher in those with active gastritis and neutrophil infiltration into the epithelium than in those with inactive gastritis. In contrast, interleukin-6 concentrations were raised in both active and inactive gastritis. This study shows that H pylori gastritis is associated with increased gastric mucosal production of TNF alpha and interleukin-6 and that the nature of the mucosal cytokine response varies with the immunohistology of the disease. Inflammatory cytokines generated locally within the gastric mucosa could be relevant to the gastric physiology of H pylori infection.

Adult↗

Evaluation of a commercial ELISA for serodiagnosis of Helicobacter pylori infection.

A commercial ELISA for the detection of Helicobacter pylori IgG antibodies was evaluated using serum from 242 patients attending an endoscopy clinic. The efficacy of the ELISA was assessed in relation to the histological detection of H pylori on antral mucosal biopsy specimens. In patients under 61 years of age (n = 138) the ELISA was 97.5% sensitive and 85.5% specific for H pylori infection, with a positive predictive value of 91% and a negative predictive value of 96%. Over the whole group the sensitivity of the ELISA was 93.8% and the specificity 79.3%. The positive predictive value and negative predictive values were, respectively, 90% and 87%. These results suggest that the Bio-Rad GAP IgG H pylori ELISA is suitable for serodiagnosis of H pylori infections for most clinical purposes and thus makes H pylori serology available to routine diagnostic laboratories.

Adult↗

Immune responses to Helicobacter pylori in children with recurrent abdominal pain.

The systemic immune response to Helicobacter pylori was examined in 69 children with recurrent abdominal pain and upper gastrointestinal symptoms. Twenty one (30%) children were histologically positive for H pylori. Eighteen of the 21 positive subjects and two H pylori negative subjects (one with normal mucosa, one with lymphocytic gastritis) were positive for H pylori IgG antibodies by enzyme linked immunosorbent assay (ELISA) (86% sensitivity, 98% specificity). In children with H pylori associated gastritis, there was a significant positive correlation (p less than 0.05) between IgG antibody titres and patient age. Intra-assay comparison of sera from histologically negative adults with those of histologically negative children showed that the cut off for positivity in the ELISA for adults was greater than that for children. Immunoblotting showed IgG positivity in 20 of the 21 patients with H pylori infection (95% sensitivity). Both ELISA and immunoblotting for IgA and IgM H pylori antibodies had poor discriminatory value for determining infection. Serological detection of H pylori IgG antibodies seems to be valuable in the assessment of children presenting with recurrent abdominal pain and other gastrointestinal symptoms, but assays must first be validated in paediatric populations.

Abdominal Pain↗

Prevalence of Helicobacter pylori in patients with end-stage renal failure and renal transplant recipients.

The prevalence of Helicobacter pylori was determined using an ELISA technique for IgG antibodies to H. pylori in 76 patients with end-stage renal failure who were receiving regular haemodialysis and 202 patients with functioning renal transplants. Twenty-seven (34%) of the haemodialysis group and 58 (29%) of the transplant group were positive for H. pylori IgG antibodies, and the prevalence did not differ significantly from that in 247 age-matched healthy controls. In the haemodialysis group, patients positive for H. pylori were older, median age 60 years (range 22-73), compared to those patients without H. pylori antibodies, median age 52 years (range 22-75), p less than 0.05, more suffered from dyspeptic symptoms, 35 vs. 10% (p less than 0.01), yet fewer had been prescribed aluminium-containing antacids, 38 vs. 78% (p less than 0.01). In the transplanted group, those positive for H. pylori were more symptomatic for dyspepsia, 30 vs. 11% (p less than 0.01), and had lower serum creatinine values, 136 +/- 10 mumol/l (mean +/- SEM) vs. 172 +/- 12 mumol/l (p less than 0.05), compared to those without H. pylori antibodies. Almost all the transplant patients with H. pylori antibodies were taking steroids (98%) compared to 84% of those without antibodies (p less than 0.05). The prevalence of antibodies to H. pylori in this study was increased in symptomatic dyspeptic subjects and reduced in those patients prescribed aluminium-containing phosphate binders.

Adult↗

Helicobacter pylori infection and inflammation.

Helicobacter pylori infection and chronic active gastritis are inextricably linked, and this organism is almost certainly responsible for inducing the resulting inflammatory changes. Acute ingestion studies have confirmed that H. pylori infection causes acute gastritis, and the progression to chronic gastritis has been documented. Duodenitis and H. pylori infection often occur concurrently, but colonization is restricted to those with significant gastric metaplasia. The association between H. pylori-induced inflammation and symptoms is at present unclear. In some treatment studies H. pylori eradication has been associated with a symptomatic response, whereas the acute inflammatory response appears frequently to subside H. pylori infection of the gastroduodenal mucosa is associated with both mucosal and systemic antibody responses. The mucosal response occurs both within the stomach and locally in the duodenum in patients with duodenitis. Mucosal cellular responses also appear active in patients with H. pylori gastritis. Cytokines are produced locally, which could have significant pathophysiologic effects. The concurrent use of non-steroidal anti-inflammatory agents in patients with H. pylori-induced gastritis may modify the subsequent inflammatory response. Although H. pylori is a major and consistent stimulus for inflammation within the gastroduodenal mucosa, our understanding of the development of these responses is far from complete. Inflammatory mediators are released during infection and probably play a major role in modulating the subsequent mucosal immune responses.

Anti-Inflammatory Agents, Non-Steroidal↗

The effect of zinc and vitamin C supplementation on the immune status of patients with Crohn's disease.

The immune status of 29 patients with Crohn's disease given oral supplements of Vitamin C, zinc or placebo for three-week periods was studied. Collectively, the patients showed T-cell hyporesponsiveness, as assessed by phytohaemagglutinin stimulation, which was significantly improved by Vitamin C. Both monocyte function, as assessed by latex phagocytosis, and pan T-Cell number were significantly reduced and were not influenced by supplementation. Humoral immunity, assessed by pokeweed mitogen-induced immunoglobulin synthesis, was normal and remained unchanged. Vitamin C supplements improved T-cell function in Crohn's disease, whereas neither Vitamin C nor zinc had a measurable effect on humoral immunity.

Journal Article↗

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↗

Soluble interleukin-2 receptor in Crohn's disease: relation of serum concentrations to disease activity.

Serum concentrations of soluble interleukin-2 receptor (sIL-2R) were measured as a marker of immune activation in a group of 30 patients with Crohn's disease. sIL-2R concentrations were determined by enzyme linked immunosorbent assay during periods of active and inactive disease and correlated with standard parameters of disease activity. Serum concentrations of sIL-2R were significantly raised in patients with active Crohn's disease compared with patients with inactive disease (p less than 0.001) and control subjects. There was a significant correlation between serum sIL-2R concentrations and disease activity as assessed by the Harvey-Bradshaw index (r = 0.42, p less than 0.01), platelet numbers (r = 0.49, p less than 0.01), and orosomucoid (r = 0.47, p less than 0.01), alpha 1 antitrypsin (r = 0.44, p less than 0.01), and C reactive protein concentrations (r = 0.48, p less than 0.001) but not with the erythrocyte sedimentation rate. Measurement of serum sIL-2R concentration is a simple and useful laboratory means of assessing disease activity. Raised concentrations in patients with active Crohn's disease is further evidence for in vivo immune activation occurring in this disease.

Adult↗

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↗

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↗