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Biomedical subjects

J O Hunter

Publications and source records attributed to J O Hunter.

At least 55 records · Page 3Linked to original sources

Treatment of active Crohn's disease by exclusion diet: East Anglian multicentre controlled trial.

Elemental diet is as effective in producing remission of Crohn's disease (CD) as is corticosteroid treatment, but most patients relapse soon after resumption of a normal diet. We have investigated the efficacies of dietary modification and oral corticosteroids in maintaining remission achieved with elemental diet. In a multicentre trial, 136 patients with active CD were started on elemental diet and other treatment was withdrawn. 43 (31%) declined to continue elemental diet for 14 days, but 78 (84%) of the remaining 93 achieved remission and were randomly assigned corticosteroids (38) or diet (40). Corticosteroid treatment started at 40 mg prednisolone daily, which was tapered and stopped after 12 weeks; that group received dietary advice on healthy eating. The diet group received "tapered" placebo and were instructed to introduce one new food daily, excluding any that precipitated symptoms. Assessment of progress for up to 2 years was made by physicians unaware of group assignment. Intention-to-treat analysis showed median lengths of remission of 3.8 (interquartile range 5.0) months in the corticosteroid group and 7.5 (15.3) months on diet, and relapse rates at 2 years, adjusted for withdrawals, of 79% and 62%, respectively (p = 0.048). Clinical improvement in the diet group was associated with significant changes in plasma albumin and alpha 1-antichymotrypsin concentrations and erythrocyte sedimentation rate. Food intolerances discovered were predominantly to cereals, dairy products, and yeast. Diet provides a further therapeutic strategy in active Crohn's disease.

Adrenal Cortex Hormones↗

Increased nitric oxide synthesis in ulcerative colitis.

Nitric oxide (NO) is produced in tissues by NO synthase with the liberation of equimolar amounts of citrulline. Citrulline concentrations were significantly higher in rectal biopsy specimens from patients with active ulcerative colitis than in those from patients with quiescent disease or with normal histology. Incubation of biopsy samples from patients with ulcerative colitis with NG-monomethyl-L-arginine (L-NMMA) inhibited citrulline production. These findings suggest that mucosal NO biosynthesis is increased in active colitis and that NO may have a pathogenic role in ulcerative colitis.

Amino Acids↗

Helicobacter pylori increases gastric antral juxtamucosal pH.

In order to examine the effect of Helicobacter pylori colonization on the gastric mucus microclimate, antral juxtamucosal pH was measured in 47 patients attending as out patients for upper gastrointestinal endoscopy. The mean pH in 28 patients negative for H. pylori was 6.40 +/- 0.24 compared to 6.88 +/- 0.16 in 19 patients who were positive (P < 0.0001). In six of seven patients who agreed to a second study, H. pylori was eradicated and the mean pH fell from 6.81 +/- 0.17 to 6.08 +/- 0.16 (P < 0.001). The pH remained high in the one patient who remained positive (6.8 and 7.0). This study provides the first in vivo evidence that H. pylori can increase the antral juxtamucosal pH and suggests that ammonia production by the organism is capable of altering gastric mucus microclimate to impair the normal negative feedback controlling gastrin release. This observation may explain the coexistence of relative hypergastrinemia and H. pylori colonization in duodenal ulcer patients.

Female↗

Nitric oxide affects mammalian distal colonic smooth muscle by tonic neural inhibition.

1 The role of the L-arginine-nitric oxide (NO) pathway in tonic neural inhibition of spontaneous mechanical activity of distal colonic circular smooth muscle (DCCSM) was investigated in male Wistar rats. 2 Muscle strips were mounted in organ baths and spontaneous contractions recorded with isometric force transducers. They were characterized as low frequency (LFCs) 0.41 +/- 0.03 N cm-2 or high frequency contractions (HFCs) 0.22 +/- 0.04 N cm-2. The latter occurred intermittently to produce summation contractions (SCs) range 0.5-12 N cm-2. 3 Tetrodotoxin (100 nM) increased the forces of LFCs and SCs. Increase in force to tetrodotoxin did not occur after incubation of the muscle with NG-monomethyl-L-arginine (L-NMMA) 500 microM, an inhibitor of NO biosynthesis. 4 L-NMMA but not its enantiomer D-NMMA increased the force of LFCs (EC50: 200 microM) and SCS (EC50:175 microM) in a concentration-dependent manner which was reversed by L-arginine but not by D-arginine. 5 Muscle, precontracted by acetylcholine, relaxed to sodium nitroprusside (EC50:1.8 microM) NO gas (EV50:70 microliters) and NO solutions (EC50:4 microM) in a concentration-dependent manner. Guanosine 3':5'-cyclic monophosphate tissue concentrations (pmol mg-1 protein) were elevated in muscle after relaxation by sodium nitroprusside (500 microM) from 0.32 +/- 0.06 to 1.2 +/- 0.37 and by 1 ml of NO gas from 0.49 +/- 0.05 to 1.54 +/- 0.14. 6 These data suggest that DCCSM is under tonic neural inhibition mediated by NO biosynthesis.

Acetylcholine↗

Relaxation of distal colonic circular smooth muscle by nitric oxide derived from human leucocytes.

The role of nitric oxide (NO) as a mediator of colonic circular smooth muscle relaxation by human leucocytes was investigated. Granulocytes and mononuclear cells were obtained by gradient centrifugation of venous blood from healthy volunteers. Both cell types relaxed precontracted distal colonic circular smooth muscle in a concentration dependent manner. Muscle relaxation was inhibited by preincubation of cells with NG-monomethyl-L-arginine (100 microM/l) but not by preincubation with NG-monomethyl-D-arginine (100 microM/l). Muscle relaxation by cells was reduced by 200 nM oxyhaemoglobin and 10 microM methylene blue but was increased by 60 units/ml superoxide dismutase. Non-viable cells did not produce muscle relaxation. Activation of mononuclear cells by incubation with 100 nM/l FMet-Leu-Phe increased muscle relaxation, whereas activation of granulocytes did not. Granulocytes and mononuclear cells relax precontracted distal colonic circular smooth muscle in vitro by the release of NO that may contribute to motility disorders of the gut associated with inflammation.

Adult↗

The role of faecal Candida albicans in the pathogenesis of food-intolerant irritable bowel syndrome.

Candida albicans was sought in stool samples from 38 patients with irritable bowel syndrome and 20 healthy controls. In only three patients with irritable bowel syndrome was C. albicans discovered and these patients had either recently received antibiotics or the stool sample had been delayed more than 24 hours in transit. C. albicans was isolated from none of the control stool samples. We conclude that C. albicans is not involved in the aetiology of the irritable bowel syndrome.

Candida albicans↗

Capillary blood flow to the skin of forearm in cirrhosis.

In liver cirrhosis a hyperkinetic circulatory state is frequently observed as a consequence of an arterial or even a venous peripheral vasodilatation with secondary increase in cardiac output. Indirect evidence suggests that, in liver disease, the manifestation of warm hands, capillary pulsation, or palmar erythema may also relate to such a state by way of an increased skin blood flow. The purpose of the present study has been to directly assess capillary skin blood flow in liver disease through the clearance of a locally injected radioactive substance. The study was performed in 24 patients with different liver diseases, including 14 Child class II cirrhotics, and in 9 control subjects. A small volume of Na 131I solution was injected at the volar surface of the forearm, and radioactive counts were recorded continuously for ten seconds every minute for up to twenty minutes. The best fit line of the disappearance rate was determined by the least square method, and both its T/2 and an estimated blood flow parameter were calculated. The T/2 of isotope disappearance rate was 4.54 +/- 0.71 and 4.38 +/- 0.68 minutes in cirrhotics and controls, respectively. Similarly, estimates of skin blood flow (mL/min/100 g tissue) were 7.82 +/- 1.28 in the cirrhotic patients, not significantly different from those in both patients with mixed liver diseases (7.6 +/- 2.86) and control subjects (8.06 +/- 1.04). Parameters of skin blood flow were also invariant in respect to the various etiologies of liver disease. Thus, the present findings indicate that capillary skin blood flow is not affected by the hyperdynamic circulatory changes occurring in liver cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Double-blind randomized multicenter study comparing Maalox TC tablets and ranitidine in healing of duodenal ulcers.

The efficacy of ranitidine 150 mg twice daily and Maalox TC three tablets four times daily were compared in patients with endoscopically confirmed duodenal ulcer. Seventy-nine patients were randomly allocated to double-blind, double-dummy treatment, stratified for smokers. Endoscopy was repeated after four weeks. Those unhealed continued treatment for a further two weeks before final endoscopy. Per protocol analysis in 53 patients showed ulcer healing rates at week 4 and at weeks 4 and 6 combined of 78 and 89% on Maalox TC, and of 81 and 91% on ranitidine, respectively. The same analysis gave overall healing rates of 81% in smokers and 100% in nonsmokers, irrespective of treatment. Both treatments provided early ulcer pain relief. Diarrhea was a commoner side effect in patients on Maalox TC. The study showed Maalox TC and ranitidine were equally effective in healing duodenal ulceration.

Adult↗

Epidermal growth factor stimulates synthesis and secretion of mucus glycoproteins in human gastric mucosa.

1. The effects of epidermal growth factor on the synthesis and secretion by human gastric mucosa of radiolabelled mucus glycoprotein have been studied in organ culture. 2. Addition of epidermal growth factor at a concentration of 5 or 10 ng/ml increased the synthesis of glycoprotein from 84 +/- 16.2 d.p.m./micrograms of protein to 132 +/- 19.5 and 156 +/- 20.2 d.p.m./micrograms of protein, respectively. The same doses increased secretion from 73.75 +/- 17 d.p.m./micrograms of protein to 114.0 +/- 26.4 and 141.5 +/- 31.4 d.p.m./micrograms of protein (P less than 0.001). 3. As glycoproteins are the main constituent of the mucus defence barrier, epidermal growth factor-stimulated mucus production may contribute to gastric cytoprotection.

Epidermal Growth Factor↗

Antacid maintenance therapy in the prevention of duodenal ulcer relapse.

The effectiveness of antacid maintenance therapy in preventing duodenal ulcer (DU) relapse was investigated. Two hundred and fifty one asymptomatic patients with healed DU were stratified into smokers and non-smokers and randomised to receive for one year either placebo, or Maalox TC three tablets (81 mmol) at bedtime (hs), or Maalox TC three tablets in the morning plus three tablets at bedtime (bd) (162 mmol), or cimetidine 400 mg at bedtime. A double dummy technique was used to render the study double blind. In 176 patients evaluable for efficacy, the cumulative relapse at one year was: placebo 57%; Maalox TC hs 39%; Maalox TC bd 23%; cimetidine 25%. Maalox TC bd and cimetidine were equally effective and superior to placebo (p less than 0.01) and bedtime Maalox TC (p less than 0.04). The benefit of treatment was significant for the overall sample and for the subgroup of smokers. The results for the non-smokers also supported efficacy for these two treatments but, perhaps because of small sample sizes, these comparisons were not significant. All 251 patients were assessed for safety. Approximately half the patients in each treatment group had adverse events, leading to withdrawal in three, seven, 12, and four patients on placebo, Maalox hs, Maalox bd, and cimetidine respectively. Diarrhoea occurred in 12 patients in Maalox TC bd and eight in each other group. Serum magnesium concentrations were unchanged; aluminium concentrations were higher than baseline at six and 12 months in both antacid groups and at 12 months in the cimetidine group but the differences were not significant. Maalox TC three tablets bd are as effective as cimetidine 400 mg at bedtime in reducing DU relapse and both are superior to placebo.

Adult↗