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Biomedical subjects

J O Hunter

Publications and source records attributed to J O Hunter.

At least 37 records · Page 2Linked to original sources

Nutritional factors in inflammatory bowel disease.

During the past 20 years there has been growing interest in the importance of nutritional factors in the pathogenesis of inflammatory bowel disease. There are so far no definite links between ulcerative colitis and diet, but links with Crohn's disease have been studied by both epidemiologists and clinicians. Epidemiological studies, although retrospective, have suggested that patients with Crohn's disease eat more sugar and sweets that control individuals; however, when dietary sugar is restricted, there is little clinical benefit. The clinical approach to nutrition in Crohn's disease has been by the use of elemental diets, which will produce symptomatic and objective remission in up to 90% of compliant patients. Those who return to normal eating soon relapse but, in some studies, have enjoyed prolonged remission on exclusion diets. The foods excluded have been not sugar, but predominantly cereals, dairy products and yeast. Attention has now switched to the possible harmful role of fat in Crohn's disease. The efficacy of elemental feeds appears to depend not on the presentation of nitrogen but on the amount of long chain triglyceride present. Increases in recent years in the frequency of Crohn's disease in Japan have been correlated with increased dietary fat intake, and a recent study suggested that W-3 fatty acids, which are metabolized by immunomodulatory leukotrienes and prostaglandins, may have a beneficial role to play. The links between nutrition and Crohn's disease have now become strong and the role of fat may be the most exciting of all.

Colitis, Ulcerative↗

Review article: the dietary management of Crohn's disease.

Enteral feeding has been shown to be as effective as primary therapy for Crohn's disease, but it requires high patient motivation, may be unpalatable and is expensive. However, in adolescents with growth failure and when corticosteroid therapy is contra-indicated or has failed, it may become the treatment of choice. Furthermore, dietary therapy allows circumvention of the adverse side-effects of repeated courses of steroids. A number of different hypotheses have been proposed to explain the effect of enteral feeds but none has reached universal acceptance. Prospective trials suggest that the exclusion of whole protein is not necessary. Comparison of feeds with differing composition suggests that a low fat content increases efficacy and various explanations have been offered. The reduction of colonic bacterial load may also be important. Because symptoms of Crohn's disease may be provoked by eating, there is a risk of falsely attributing symptoms to specific foodstuffs. However, in many individuals foods can be identified which affect disease activity, and their exclusion leads to prolongation of disease remission. Dietetic supervision during food testing is important to avoid detrimental effects on nutrient and micronutrient intake.

Clinical Trials as Topic↗

Confirmation of nitric oxide synthesis in active ulcerative colitis by infra-red diode laser spectroscopy.

BACKGROUND: The synthesis of nitric oxide (NO) in the colonic mucosa of patients affected by ulcerative colitis (UC) has been previously investigated using indirect measurements of enzyme activity and non-specific measurements of luminal NO gas. The aim of this study was to determine unequivocally if luminal NO gas in active UC is present in greater concentrations than in healthy control subjects. METHODS: Luminal gas was collected from eight patients with active UC and eight healthy volunteers. NO gas concentration was measured using diode laser spectroscopy. RESULTS: NO gas was detected in four of eight patients with active UC (range 0.13-1.1 nmol) and none of the healthy control subjects. CONCLUSION: NO gas is present in greater concentrations in patients with active UC than in control subjects. This supports the view that mucosal NO synthesis is increased in ulcerative colitis.

Colitis, Ulcerative↗

Xanthine oxidase activity is not increased in the colonic mucosa of ulcerative colitis.

AIM: To measure urate and xanthine by high-performance liquid chromatography in mucosal biopsies from patients with ulcerative colitis and controls. RESULTS: Reactive oxygen metabolite activity was demonstrated by a cystine to cysteine ratio of 0.24 +/- 0.08 in the control biopsies compared with 1.79 +/- 0.25 in ulcerative colitis. The product to substrate ratio (urate to xanthine) for xanthine oxidase and mucosal urate concentrations were not different between ulcerative colitis patients and controls. Xanthine oxidase activity after incubation of homogenized biopsies was 0.451 (+/- 0.175) nmol.min/mg protein in ulcerative colitis patients compared with 2.585 (+/- 0.823) nmol.min/mg protein in controls (P < 0.01). CONCLUSION: These results suggest that xanthine oxidase may not be the major source of superoxide formation in ulcerative colitis.

Biopsy↗

The effect of a non-absorbable fat substitute, sucrose polyester, on gastrointestinal function.

OBJECTIVES: To assess the effects of a single dose of a non-absorbable fat substitute, sucrose polyester, on gastrointestinal function. METHODS: The effects of 50 g of sucrose polyester taken as a single drink on gastric emptying, small bowel transit time (SBTT), whole gut transit time (WGTT) and faecal weight compared with a control fat were examined in double-blind studies. The effect of sucrose polyester on gallbladder ejection fraction and gastrointestinal hormones was also assessed. RESULTS: Sucrose polyester was found to accelerate gastric emptying significantly (98.33 +/- 71.0 vs. 112.92 +/- 82.0 min, P = 0.042) but to slow SBTT (153.75 +/- 36.25 vs. 128.75 +/- 47.39 min. P = 0.006). A trend to faster WGTT (37.47 +/- 15.61 vs. 46.63 +/- 20.65 h) and increased faecal weight was observed (453.33 +/- 122.05 vs. 395.0 +/- 107.85 g/48 h), but this did not reach statistical significance. There was a striking reduction in gallbladder ejection fraction with sucrose polyester (21.69 +/- 25.32 vs. 45.27 +/- 27.67%), P = 0.039) and a corresponding significant decrease in the release of cholecystokinin. Lower levels of motilin and enteroglucagon were also observed. CONCLUSIONS: Sucrose polyester has significant effects on gastrointestinal transit, gallbladder contraction and gastrointestinal hormones. These effects can be explained on the basis of decreased luminal products of digestion and may have implications for the widespread use of sucrose polyester as a fat substitute.

Administration, Oral↗

Accuracy of serology for the diagnosis of Helicobacter pylori infection--a comparison of eight kits.

AIMS: To determine the accuracy of eight commercially available kits for the serological diagnosis of Helicobacter pylori infection, and hence whether a serology service could be introduced to reduce endoscopy workload. METHODS: Eighty four patients newly presenting to their general practitioners with dyspepsia were recruited. Gold standard diagnosis of H pylori infection was obtained both by a histological examination of gastroduodenal biopsy specimens and by the 14C-urea breath test (UBT). The performance of six quantitative and two qualitative enzyme linked immunosorbent assays for H pylori IgG, used according to the manufacturers' instructions, with serum samples obtained during the endoscopy visit, were compared. RESULTS: The study population had a median age of 45 years, and the prevalence of H pylori infection was 35%. With one exception, where the patient had received a course of anti-H pylori treatment between endoscopy and UBT, there was 100% concordance in the results of the two gold standard techniques. Discordant serology results were more common in patients aged > 50 years (42% of the total) than in younger patients (21%), and this was most noticeable in uninfected patients. The sensitivity of the kits was good (90-100%), but specificity was more variable (76-96%), and the rate of equivocal results was unacceptably high in some cases (0-12%). The overall accuracy of the kits ranged from 83 to 98%. Two kits in particular performed well (Pylori-Elisa II, Bio-Whitaker and Premier, Launch; qualitative) with 98% and 100% accuracy, respectively. CONCLUSIONS: In a symptomatic population with a prevalence of H pylori infection of 35%, particularly in patients aged < 50 years, some but not all serology kits may be used as a highly accurate and inexpensive alternative to the gold standard techniques.

Adult↗

Long-chain triglycerides reduce the efficacy of enteral feeds in patients with active Crohn's disease.

Elemental diets are effective treatments for active Crohn's disease. To determine which dietary constituents are of therapeutic importance, the effectiveness of four separate feeds was related to their compositions, and the findings substantiated by meta-analysis of previous dietary studies. 76 patients with active Crohn's disease were recruited. 17 were randomised to an amino acid-based elemental diet (E028), 22 to E028 with added long-chain triglyceride (E028 LCT), 18 to a semi-elemental, peptide based diet (Pepdite 2+) and 19 received E028 with added medium-chain triglyceride (E028 MCT). Disease activity fell in all groups and remission rate was negatively correlated with the amount of energy derived from LCT (r = -0.97, p = 0.016). Inflammatory indices fell in the groups (E028 + E028 MCT) containing least LCT. No other dietary constituents correlated with remission rate. A meta-analysis of published studies confirmed a negative correlation between remission rate and LCT (r = -0.63, p = 0.006) but not other constituents. The association between dietary LCT and remission rate may have pathogenic significance and allow the development of more effective enteral feeds.

Journal Article↗

The effects of elemental diet and subsequent food reintroduction on rheumatoid arthritis.

The role of diet in rheumatoid arthritis (RA) remains controversial and there have been no controlled studies on the use of elemental diet in the treatment of RA. Elemental diet is an hypoallergenic protein-free artificial diet consisting of essential amino acids, glucose, trace elements and vitamins. This study was carried out to assess the role of elemental diet and subsequent food reintroduction in RA. Elemental diet (E028) (and a small number of foods) was given to 24 patients with definite RA in order to induce a remission and then foods were gradually introduced. Where a food was suspected of causing symptoms it was removed from the diet. Twenty-three control patients supplemented their usual diet with E028. After the elemental diet there was a statistically significant improvement in the diet group in grip strength (P = 0.008) and Ritchie score (P = 0.006) but not in ESR, CRP, thermographic joint score or functional score. The diet group lost more weight than the control group and this correlated with the improvement in grip strength. This improvement was not present following food reintroduction. As the improvements took place in more subjective disease parameters and because of the difficulties in adequately blinding studies of diet in arthritis, a placebo effect must be considered. There was a high default rate, only 38% of those patients originally enrolled completed the study. In conclusion, this study shows that elemental diet can cause an improvement in a number of disease parameters in RA but this is not sustained by an individualized diet. It also illustrates some of the difficulties involved in the study of diet in arthritis.

Adult↗

The effects of aminosalicylic acid derivatives on nitric oxide in a cell-free system.

AIMS AND METHODS: To determine the effect of aminosalicylic acid derivatives on the concentration of nitric oxide produced in a cell-free system, by the use of a sensitive and specific polarographic meter. RESULTS: The aminosalicylic acid derivatives 3-ASA (IC50 100 microM), 4-ASA (IC50 350 microM) and 5-ASA (IC50 5 microM) all decreased the nitric oxide signal. These drugs had a similar inhibitory effect on the formation in vitro of nitrite from sodium nitroprusside (IC50: 200 microM, 500 microM and 100 microM, respectively). Sulphasalazine (31.1 +/- 5% decrease in signal at 1 mM) was less effective than 5-ASA, but sulphapyridine, N-acetyl 5-ASA, indomethacin and hydrocortisone produced no decrease in nitric oxide signal at all. CONCLUSIONS: Nitric oxide binding may be part of the mechanism by which ASA derivatives exert their therapeutic effect, and this work suggests that it may be an important factor in the pathogenesis of ulcerative colitis.

Aminosalicylic Acids↗

Endoscopic balloon dilatation of duodenal strictures in Crohn's disease.

Endoscopic balloon dilatation of oesophageal and colonic strictures is now widely performed. Duodenal strictures due to Crohn's disease represent a difficult clinical problem as surgical intervention is a major undertaking and recurrences are common. We describe endoscopic balloon dilatation in three patients with obstructive symptoms from duodenal strictures due to Crohn's disease. The procedure appeared safe, was well tolerated and resulted in an excellent symptomatic response. This method is particularly suitable for short duodenal strictures and avoids the need for surgical intervention in this difficult group of patients.

Adult↗

Validation of 99Tcm-HMPAO leucocyte scintigraphy in ulcerative colitis by comparison with histology.

Leucocyte scintigraphy offers an alternative to more invasive techniques in the investigation of inflammatory bowel disease. The accuracy of 99Tcm-HMPAO leucocyte scintigraphy has not been assessed by comparison with colonic histology, which was the aim of this study. 15 patients with ulcerative colitis underwent 99Tcm-HMPAO leucocyte scintigraphy (TLS) less than 5 days before colonoscopy. Histological features of mucosal biopsies were compared with total and segmental colonic TLS scores. Segmental and total scintigraphy scores correlated most strongly with histological grades for acute inflammation (r = 0.75, p < 0.001 and r = 0.9, p < 0.001, respectively) and chronic inflammatory cell infiltration in the lamina propria (r = 0.76, p < 0.001 and r = 0.86, p < 0.001, respectively). 99Tcm-HMPAO leucocyte scintigraphy detected acute inflammation in the colon of patients with ulcerative colitis with a sensitivity of 91% and negative predictive value of 80% and localized acute inflammation to a particular colonic segment with a sensitivity of 82%, specificity of 94%, accuracy of 88%, positive predictive value of 94% and negative predictive value of 91%. 99Tcm-HMPAO leucocyte scintigraphy positivity predicts and localizes colonic acute inflammation with a high degree of confidence, but negative scintigraphy does not exclude acute inflammation.

Adult↗

Increased gastric juice epidermal growth factor after non-steroidal anti-inflammatory drug ingestion.

Epidermal growth factor (EGF), present in saliva and gastric juice, is a potent mitogen and an important element of mucosal defence. Changes in salivary and gastric juice epidermal growth factor in response to non-steroidal anti-inflammatory drug (NSAIDs) ingestion were measured to assess the role of EGF in gastric mucosal adaptation to NSAIDs. Patients with arthritis underwent endoscopy with collection of saliva and gastric juice for EGF measurement, before and two weeks after continuous NSAID ingestion. During this period patients also received either the prostaglandin analogue misoprostol or placebo in addition to their NSAID. In the misoprostol group (n = 5) there was no observed mucosal damage and no change in either salivary or gastric juice EGF. In the placebo group (n = 10) three patients developed erosions. Salivary EGF did not change (mean (SEM) 3.02 (0.54) ng/ml v 2.80 (0.41) ng/ml) but gastric juice EGF increased from 0.42 (0.12) ng/ml to 0.69 (0.14) ng/ml (p < 0.05). This increased EGF could contribute to the increased cellular proliferation observed during NSAID ingestion and may represent an important mechanism underlying gastric mucosal adaptation.

Anti-Inflammatory Agents, Non-Steroidal↗