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Biomedical subjects

S P Travis

Publications and source records attributed to S P Travis.

At least 19 recordsLinked to original sources
PubMed2001

Treatment of intestinal Behçet's syndrome with chimeric tumour necrosis factor alpha antibody.

Few patients with Behçet's syndrome have gastrointestinal ulceration. Such patients are difficult to treat and have a higher mortality. Faced with refractory symptoms in two patients with intestinal Behçet's, we used the tumour necrosis factor alpha (TNF-alpha) monoclonal antibody infliximab to induce remission. Both women (one aged 27 years, the other 30 years) presented with orogenital ulceration, pustular rash, abdominal pain, bloody diarrhoea due to colonic ulceration, weight loss, and synovitis. One had thrombophlebitis, digital vasculitis, perianal fistula, and paracolic abscess; the other had conjunctivitis and an ulcer in the natal cleft. Treatment with prednisolone, methyl prednisolone, and thalidomide in one and prednisolone, colchicine, and cyclosporin in the other was ineffective. After full discussion, infliximab (3 mg/kg, dose reduced because of recent sepsis in one, and 5 mg/kg in the other) was administered. Within 10 days the ulcers healed, with resolution of bloody diarrhoea and all extraintestinal manifestations. A second infusion of infliximab was necessary eight weeks later in one case, followed by sustained (>15 months) remission on low dose thalidomide. Remission was initially sustained for 12 months in the other but thalidomide had to be stopped due to intolerance, and a good response to retreatment lasted only 12 weeks without immunosuppression, before a third infusion. The cause of Behçet's syndrome is unknown but peripheral blood CD45 gammadelta T cells in Behçet's produce >50-fold more TNF-alpha than controls when stimulated with phorbol myristate acetate and anti-CD3. Infliximab could have a role for inducing remission in Behçet's syndrome.

Adult↗
PubMed1997

Review article: insurance risks for patients with ulcerative colitis or Crohn's disease.

Prospective population-based studies have allowed a re-evaluation of the risks of insuring patients with ulcerative colitis or Crohn's disease. Life expectancy, the risk of cancer and working capacity are very much better than previously recognised and are normal for many patients. Three population-based studies in ulcerative colitis have shown a mortality similar to or slightly less than the general population except in the first year after diagnosis, whilst two have shown a slightly higher mortality (standardized mortality ratio, SMR = 1.4), except for those with proctitis. In Crohn's disease, two population-based studies have also shown an increased mortality (SMR = 1.4), which is similar to that of unskilled manual labourers (SMR = 1.43) from all causes of death. Three other studies have shown no increase in overall mortality, except in the first 5 years after diagnosis, in those with proximal small intestinal disease and in some patients needing multiple operations. Insurance risks should be evaluated on an individual basis, after details of the extent and pattern of disease have been obtained. Although the 'standard life' in insurance terms differs from that of the general population, because people who seek life assurance are self-selected from a more affluent section of society, many patients can be identified who have a particularly good prognosis. These include patients with ulcerative proctitis, those with left-sided colitis in extended remission (> 12 months), and patients more than 30 years old with localized ileal or ileocaecal Crohn's disease that has responded to treatment. From the published data, it is difficult to justify increasing the insurance premium in such patients.

Activities of Daily Living↗
PubMed1997

Achalasia presenting as acute stridor.

We report a case of achalasia presenting as acute stridor and respiratory distress in an 87-year-old woman. A mega-oesophagus was decompressed by aspiration through a naso-oesophageal tube, stiffened with paediatric endoscopic biopsy forceps before placement. Subsequent barium swallow showed mega-oesophagus secondary to achalasia causing tracheal compression at the level of the thoracic inlet. There have been 28 previous case reports of mega-oesophagus due to achalasia causing tracheal obstruction and the literature is reviewed. Recognition and urgent treatment of this very rare complication of achalasia by naso-oesophageal decompression may avoid fatality.

Aged↗
PubMed1996

Predicting outcome in severe ulcerative colitis.

BACKGROUND: Simple criteria are needed to predict which patients with severe ulcerative colitis will respond poorly to intensive medical treatment and require colectomy. AIMS: To find out if the early pattern of change in inflammatory markers or other variables could predict the need for surgery and to evaluate the outcome of medical treatment during one year follow up. PATIENTS: 51 consecutive episodes of severe colitis (Truelove and Witts criteria) affecting 49 patients admitted to John Radcliffe Hospital, Oxford. METHODS: Prospective study monitoring 36 clinical, laboratory, and radiographic variables. All episodes treated with intravenous and rectal hydrocortisone and 14 of 51 with cyclosporine. RESULTS: Complete response in 21 episodes (< or = 3 stools on day 7, without visible blood), incomplete response in 15 (> 3 stools or visible blood on day 7, but no colectomy), and colectomy on that admission in 15. During the first five days, stool frequency and C reactive protein (CRP) distinguished between outcomes (p < 0.00625, corrected for multiple comparisons) irrespective of whether patients or the number of episodes were analysed. It could be predicted on day 3, that 85% of patients with more than eight stools on that day, or a stool frequency between three and eight together with a CRP > 45 mg/l, would require colectomy. For patients given cyclosporine, four of 14 avoided colectomy but two continued to have symptoms. After admission, complete responders remained in remission for a median nine months and had a 5% chance of colectomy. Incomplete responders had a 60% chance of continuous symptoms and 40% chance of colectomy. CONCLUSIONS: After three days intensive treatment, patients with frequent stools (> 8/day), or raised CRP (> 45 mg/l) need to be identified, as most will require colectomy on that admission. The role of cyclosporine for treating severe colitis has yet to be defined. After seven days' treatment, patients with > 3 stools/day of visible blood have a 60% chance of continuous symptoms and 40% chance of colectomy in the following months.

Adult↗
PubMed1995

Site of action of platelet-activating factor within the mucosa of rabbit distal colon.

1. To determine how platelet-activating factor stimulates colonic anion secretion and increases epithelial permeability, epithelial sheets of rabbit distal colon excluding the submucosal neural plexus were mounted in Ussing chambers. The influence of specific inhibitors and 50 nmol/l platelet-activating factor on short-circuit current and transepithelial resistance was then investigated. 2. Pretreatment with 1 mumol/l indomethacin or 1 mumol/l doxantrazole abolished the biphasic stimulation of the short-circuit current and decrease in transepithelial resistance induced by platelet-activating factor. Addition of 10 mumol/l mepyramine attenuated the early phase and completely inhibited the late phase. Pretreatment with 1 mumol/l ranitidine, 0.1 mumol/l tetrodotoxin, 0.1 mumol/l ritanserin or a 5-lipoxygenase inhibitor (1 mumol/l MK886) had no effect. 3. To assess the influence of platelet-activating factor on epithelial function isolated from lamina propria elements, monolayers were cultured from a human colonic epithelial cell line (T-84). 4. The short-circuit current across monolayers mounted in Ussing chambers stimulated by 10 mumol/l ionomycin could be inhibited by pretreatment with ouabain or frusemide, consistent with the capacity for chloride secretion. Addition of platelet-activating factor (up to 500 nmol/l) had no effect on short-circuit current or transepithelial resistance. Receptor expression was examined with [3H] platelet-activating factor in isolated T-84 and HT-29 cells and found to be absent. 5. The influence of physiological concentrations of platelet-activating factor on colonic epithelial anion secretion and increased permeability in rabbit distal colon is indirect and consistent with mediation by prostaglandins released from mucosal mast cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Pelvic and perineal complications of Crohn's disease: assessment using magnetic resonance imaging.

This study evaluated the role of magnetic resonance imaging (MRI) in the demonstration of the pelvic and perianal complications of Crohn's disease. Twenty five patients with active Crohn's disease were studied (12 male; mean age 41.1 years). MRI examinations were performed using a 1.5 Tesla system, within 14 days after clinical assessment. T1 and T2 weighted fast spin echo sequences in two or three orthogonal planes were performed, with fat suppression in some cases. The MRI results were correlated with surgical and clinical findings. In 16 patients, cutaneous, deep perineal or enterovesical fistulas or abscesses were diagnosed at MRI which showed close correlation with findings at examination under anaesthetic. In eight patients no fistulas or abscesses were seen at MRI nor was there any evidence of complications on clinical examination and flexible sigmoidoscopy. There was one false negative examination in a patient who had a colovesical fistula. In conclusion, MRI can accurately show the pelvic and perineal complications of Crohn's disease and may render examination under anaesthetic unnecessary.

Abdominal Abscess↗
PubMed1995

Are serum concentrations of nitric oxide metabolites useful for predicting the clinical outcome of severe ulcerative colitis?

OBJECTIVE: To determine serum concentrations of nitric oxide metabolites (NOX) in patients with severe ulcerative colitis and to assess whether these concentrations predict clinical outcome. PATIENTS: Twenty-six patients (16 men and 10 women, mean age 46 years) with severe ulcerative colitis requiring hospitalization for parenteral steroid therapy. Thirteen patients had a complete clinical response and symptoms resolved after 5 days of parenteral steroid administration; 13 made an incomplete recovery and needed further treatment (six cyclosporin, seven colectomy). METHODS: Serum concentrations of NOX and C-reactive protein (CRP) were measured daily for 3 days in all patients and as clinically indicated thereafter. The normal range for NOX was established by measuring the concentration in 25 healthy controls. RESULTS: Mean serum NOX and CRP concentrations were significantly elevated in both the patients with a complete and those with an incomplete response compared with controls (P < 0.001) on day 1 and fell during the first 3 days of therapy. On day 3, mean serum concentrations of NOX and CRP were lower in the patients with a complete response, but only the difference in CRP attained statistical significance (P = 0.02). There was no correlation between NOX and CRP concentrations. CONCLUSIONS: In the majority of patients with severe ulcerative colitis, circulating concentrations of NOX are increased at presentation and fall promptly during parenteral steroid therapy, irrespective of clinical outcome. However, in a small number of patients NOX concentrations do not fall during steroid treatment and such patients will probably require additional medical therapy or surgery.

Adult↗
PubMed1994

Salicylates for ulcerative colitis--their mode of action.

Delivery of 5-aminosalicylic acid to the colon by sulphasalazine, other azo-bonded compounds and controlled-release preparations is introduced in the context of metabolism by epithelial cells and therapeutic efficacy in ulcerative colitis. Potential modes of action are then reviewed, including actions on luminal bacteria, epithelial cell surface receptors, cellular events (such as nitric oxide release or butyrate oxidation), electrolyte transport and epithelial permeability. Evidence for an influence of salicylates on circulating and lamina propria inflammatory cells is presented, as well as actions on adhesion molecules, chemotactic peptides and inflammatory mediators, such as eicosanoids, platelet-activating factor, cytokines or reactive oxygen metabolites. The precise mechanism will remain uncertain as long as the aetiology of ulcerative colitis is unknown, but a pluripotential mode of action of salicylates is an advantage when influencing the network of events that constitute chronic inflammation.

Cell Adhesion Molecules↗
PubMed1994

Salicylates for inflammatory bowel disease.

Targeted delivery of 5-aminosalicylic acid to the small intestine and colon by controlled-release or azo-bonded compounds potentially offers treatment for ileal Crohn's disease as well as ulcerative colitis. The pharmacokinetics of sulphasalazine and aminosalicylate derivatives have been discussed and potential modes of action reviewed. These include actions on epithelial cell-surface receptors, cellular events and barrier function. Evidence for an influence of salicylates on circulating and tissue inflammatory cells is presented, as well as actions on adhesion molecules, chemotactic peptides, eicosanoids, cytokines and reactive oxygen metabolites. The precise mechanism remains unknown, but a pluripotential mode of action is an advantage when influencing the network of events that constitutes chronic inflammation. Controlled clinical trials of salicylates in ulcerative colitis and Crohn's disease have been reviewed. Their main role remains as maintenance therapy for ulcerative colitis, but relatively high doses of controlled-release preparations benefit patients with ileal Crohn's disease, following resection, or those who have recently relapsed. Finally, issues of clinical relevance have been addressed, including the choice of salicylate and safety, indications for initiating therapy, dose and duration of treatment, role in managing refractory colitis and future developments.

Aminosalicylic Acids↗
PubMed1994

Optimum dose of olsalazine for maintaining remission in ulcerative colitis.

To evaluate the optimum dose of olsalazine for maintaining remission in ulcerative colitis, 198 patients in remission for more than three months were randomly assigned to receive 0.5 g, 1.0 g, or 2.0 g/day for 12 months. A dose-ranging effect was detected in the per protocol analysis, with remission rates of 60% (0.5 g), 70% (1.0 g), and 78% (2.0 g) (p = 0.03, trend in proportions). The higher dose was most effective in patients with proctitis (90% remission on 2 g/day, p = 0.03) or those in remission for less than 12 months before the trial (88% remission on 2 g/day, p = 0.0006). There was little dose-ranging effect in patients with extensive colitis or those in remission for more than 12 months. Diarrhoea necessitated treatment withdrawal in 12%. The optimal dose of olsalazine for maintaining remission in ulcerative colitis is 1 g/day. For patients with proctitis or recent relapse, 2 g/day may be preferable, although the dose seems to be less important in patients with more extensive disease or those in long term remission.

Aminosalicylic Acids↗
PubMed1994

Intestinal carbohydrate absorption and permeability at high altitude (5,730 m).

To investigate the effects of high altitude on intestinal function, the absorption and permeation of nonmetabolizable carbohydrates were measured in 14 volunteers (median age 21 yr, range 19-37 yr) at sea level in Oxford, UK; at 1,050 m in Nepal; at 5,570 m after 5 days at > 5,500 m; and at 5,730 m after 11 days at > 5,500 m. Body weight decreased 5.7 +/- 1.19 kg from sea level to 5,570 m (P < 0.001 by paired t test) despite 72-h dietary records showing no change in energy intake. Absorption of carbohydrates by mediated transport was measured by urinary xylose and 3-O-methyl-D-glucose excretion. Xylose excretion (%oral dose) decreased from 31.4 +/- 4.5% to 20.7 +/- 4.5% (P < 0.001) and 3-O-methyl-D-glucose excretion decreased from 39.7 +/- 6.1 to 33.7 +/- 7.0% (P = 0.003) from sea level to 5,730 m. Monosaccharide permeation measured by L-rhamnose excretion decreased from 11.3 +/- 2.5 to 6.2 +/- 2.0% (P = 0.001). Intestinal permeability, a measure of barrier function (ratio of lactulose to L-rhamnose), increased from 0.036 +/- 0.014 at sea level to 0.084 +/- 0.042 at 1,050 m (P = 0.006), possibly due to infective enteropathy after arrival in Nepal, but reverted to normal (0.045 +/- 0.013; P = 0.062) at 5,730 m. Absorption of all carbohydrates returned to normal after return to the UK. This study showed that a decrease in mediated (D-xylose or 3-O-methyl-D-glucose) and diffusional (L-rhamnose) monosaccharide absorption occurs at high altitude but that intestinal permeability at 5,730 m is unchanged.

3-O-Methylglucose↗
PubMed1992

Regional differences in the response to platelet-activating factor in rabbit colon.

1. Platelet-activating factor is an inflammatory mediator related to eicosanoids which is known to stimulate anion secretion in the distal colon. Since there are regional differences in ion transport within the colon, the influence of platelet-activating factors on ion transport and epithelial permeability has been studied in rabbit caecum and distal colon mounted in Ussing chambers. 2. The effect of platelet-activating factor (1-50 nmol/l) on net electrogenic ion transport was to stimulate a biphasic increase in short-circuit current in the distal colon but not in the caecum. The platelet-activating factor-induced rise in short-circuit current was shown by ion replacement and pharmacological inhibitor studies to be consistent with chloride and bicarbonate secretion in the early phase, but with chloride secretion alone in the later phase. The effect on ion transport was specific and reversible and was enhanced by 0.25% BSA. 3. Colonic permeability, assessed by transmucosal resistance and mannitol flux, was increased by platelet-activating factor in both the distal colon and the caecum. This was consistent with an effect on platelet-activating factor on the paracellular pathway, because resistance decreased even when transcellular chloride transport was inhibited by frusemide or ion replacement. A specific platelet-activating factor antagonist (U66985) inhibited the effects of platelet-activating factor in both the distal colon and the caecum. 4. The results show that platelet-activating factor stimulates anion secretion only in the distal colon, but increases permeability in both the caecum and the distal colon.

Animals↗