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Biomedical subjects

R N Allan

Publications and source records attributed to R N Allan.

At least 19 recordsLinked to original sources
PubMed1995

Occult small bowel adenocarcinoma complicating Crohn's disease: a report of three cases.

Three patients with Crohn's disease are described who were treated by ileal resection for intestinal obstruction. Histological examination of the resected specimen in each case established the diagnosis of adenocarcinoma of the small intestine complicating Crohn's disease. This diagnosis should be considered in patients with longstanding macroscopic Crohn's disease who present with severe or recurrent symptoms. The diagnosis may not be apparent on routine radiological examination or even macroscopically at laparotomy.

Adenocarcinoma↗
PubMed1994

Pathogenesis of gall stones in Crohn's disease: an alternative explanation.

The increased prevalence of gall stones in Crohn's disease is thought to be related to depletion of the bile salt pool due either to terminal ileal disease or after ileal resection. This study was designed to examine whether this hypothesis is correct and explore alternative explanations. Two hundred and fifty one randomly selected patients (156 females, 95 males, mean age 45 years) were interviewed and screened by ultrasonography to determine the prevalence of gall stones in a large population of patients with Crohn's disease. Sixty nine (28%) patients had gall stones proved by ultrasonography (n = 42), or had had cholecystectomy for gall stone disease (n = 27). The risk factors for the development of gall stones including sex, age, site, and duration of disease, and previous intestinal resection were examined by multivariate analysis. Age and duration of disease were positive risk factors for gall stones and were covariables. The site of disease and of previous intestinal resection did not predispose to gall stones. Previous surgery was an independent risk factor for the development of gall stones, the risk increasing with number of laparotomies. It is suggested that mechanisms other than ileal dysfunction may predispose to gall stones. Postoperative gall bladder hypomotility with biliary sludge formation may be precursors of gall stone formation in patients with Crohn's disease.

Adolescent↗
PubMed1994

Ulcerative colitis and Crohn's disease: a comparison of the colorectal cancer risk in extensive colitis.

The risk of developing colorectal cancer has been compared in two identically selected cohorts of patients with extensive Crohn's colitis (n = 125) and extensive ulcerative colitis (n = 486). In both groups the effects of selection bias have been reduced wherever possible. There was an 18-fold increase in the risk of developing colorectal cancer in extensive Crohn's colitis and a 19-fold increase in risk in extensive ulcerative colitis when compared with the general population, matched for age, sex, and years at risk. The absolute cumulative frequency of risk for developing colorectal cancer in extensive colitis was 8% at 22 years from onset of symptoms in the Crohn's disease group and 7% at 20 years from onset in the ulcerative colitis group. The relative risk of colorectal cancer was increased in both ulcerative colitis and Crohn's disease among those patients whose colitis started before the age of 25 years. Whether the absolute risk is greater in the younger age group or merely reflects that the expected number of carcinomas increases with age is uncertain. While there is an increased risk of developing colorectal cancer in extensive colitis the number of patients with Crohn's disease who actually develop colorectal cancer is small because many patients with extensive Crohn's colitis undergo colectomy early in the course of their disease to relieve persistent symptoms unresponsive to medical treatment.

Adolescent↗
PubMed1994

Surgical resections in parous patients with distal ileal and colonic Crohn's disease.

The surgical resection rates among parous women with distal ileal and colonic Crohn's disease have been compared with resection rates among distal ileal (n = 197) and colonic (n = 332) Crohn's disease patients. Thirty of 44 parous women with distal ileal Crohn's disease and 28 of 44 with colonic Crohn's disease had achieved their first pregnancy on average 8 years and 6.2 years respectively before the diagnosis of Crohn's disease was established. Resections for each patient were negatively correlated with parity in both groups. (Distal ileal disease (p = 0.034, rs = 0.3207), colonic disease (p = 0.051, rs = -0.2960)). Patients with distal ileal Crohn's disease and a history of pregnancy at diagnosis (n = 30, mean follow up = 15 years) had fewer resections/patient when compared with the published resection group: mean (SD); 1.17 (0.65) v 1.57 (1.05), p = 0.006. Patients with colonic Crohn's disease and a history of pregnancy at diagnosis (n = 28, mean follow up = 16.5 years) had fewer resections/patient when compared with the published resection group: mean (SD); 0.68 (0.77) v 1.05 (0.77), p = 0.019. In summary, patients with distal ileal and colonic Crohn's disease, who had been pregnant in the past subsequently need fewer surgical resections. Pregnancy could influence the natural history of Crohn's disease either by decreasing immune responsiveness or by retarding fibrous stricture formation, which is the commonest indication for surgical intervention.

Adolescent↗
PubMed1994

Crohn's disease and colorectal cancer.

The colorectal cancer risk in Crohn's disease eliminating all known biases was assessed in a cohort of 281 patients with Crohn's disease who resided in the West Midlands at the time of diagnosis, and were first seen within five years of onset of symptoms between 1945-1975. All patients were 15 years of age or more at onset and were followed up from 12-35 years (total 5213 person years at risk (PYR)). The colorectal cancer risk in the series compared with the risk in the general population was computed by applying sex and age specific PYRs to the date of death or end of the study period 31 December 1991. There were six colonic and two rectal cancers. Six of the eight colorectal cancers were diagnosed 20 or more years after the onset of Crohn's disease. The relative risk (RR) of colorectal cancer for the series as a whole was 3.4 (p < 0.001), with a fivefold excess in the colon, but no significant excess in the rectum. Patients with extensive colitis showed an 18-fold increase in risk (RR = 18.2, p < 0.001), which decreased with increasing age at onset. This study shows that there is a statistical excess risk of developing colorectal cancer in patients who develop their Crohn's disease at a young age of onset (less than 30 years of age).

Adolescent↗
PubMed1994

Interrelation of strongyloidiasis and tuberculosis.

A 31 year old man from Gambia, resident in the United Kingdom for two years, presented with a two month history of unproductive cough, malaise, weight loss, non-specific abdominal pain, and episodic diarrhoea. Acid alcohol fast bacilli were identified in his sputum, together with Strongyloides stercoralis larvae and Giardia lamblia cysts in his stools. This case illustrates that latent strongyloidiasis can become overt in the presence of tuberculosis, and the diagnosis of strongyloidiasis must be borne in mind in patients who have previously resided in endemic regions.

Adult↗
PubMed1993

Fecal diversion in the management of Crohn's disease of the colon.

The clinical course of 44 patients undergoing elective proximal fecal diversion for Crohn's disease of the colon is reported. Sustained disease remission was obtained in 31 patients (70 percent). Diversion was associated with a significant reduction in steroid requirements (P < 0.01) and a significant improvement in hemoglobin (P < 0.001), erythrocyte sedimentation rate (P < 0.001), and albumin (P < 0.05). Sixteen patients (36.4 percent) have required a proctocolectomy, 19 patients (43.2 percent) remain defunctioned, and four patients (9 percent) have died. Five patients have had intestinal continuity restored, which has remained intact in four patients for a mean follow-up of 99 (range 21-153) months. Fecal diversion for Crohn's disease of the colon produces a high incidence of sustained disease remission, but for the majority of patients the prospect of future restoration of intestinal continuity is limited.

Adolescent↗
PubMed1993

Diffuse jejunoileitis of Crohn's disease.

Diffuse jejunoileitis is an uncommon, but important manifestation of Crohn's disease because of the associated high morbidity and challenges in medical management. Despite this there have been no studies of prognosis or management of diffuse jejunoileitis for nearly 20 years. This study analysed the outcome among 34 patients (20 women and 14 men) with diffuse jejunoileitis diagnosed between 1960 and 1991 including clinical features, medical and surgical management, death rates, current status, and prognosis. Diffuse jejunoileitis presents in younger patients (mean age at diagnosis 26.4 years) than those with distal ileal Crohn's disease (mean age at diagnosis 33.3 years). Nearly all presented with clear cut abdominal symptoms including a combination of colicky abdominal pain (91%), weight loss (62%), and diarrhoea (53%). Most patients had severe symptoms reflected by the fact that 77% had been treated with corticosteroids for periods of more than six months at some stage during their follow up. The mean follow up from diagnosis was 16 years. Twenty eight patients (82%) had at least one operation for diffuse jejunoileitis and two thirds of the patients (n = 21) required two or more operations. The frequency of surgical intervention was particularly high in the younger patients (r = 0.71, p < 0.001). The proportion of patients requiring surgery was highest in the first year after diagnosis. The annual operative rate was 15% for the first 10 years and then it fell to 5.2% in years 11-15, and 2.6% in years 16-20. The data suggest that the disease does burn itself out over time. The increasing use of strictureplasty for short strictures and the minimal use of resection has eliminated problems associated with the short small bowel syndrome. The longterm prognosis of this patients is good. Only two patients died (one of perforation of the jejunum and another of an unrelated bronchogenic carcinoma). After a mean interval from diagnosis of 16 year, 24 of 32 living patients are well and symptom free. Only eight have abdominal symptoms of whom three are receiving corticosteroid treatment and one azathioprine. The combination of anti-inflammatory drugs with the relief of recurrent obstructive symptoms by strictureplasty can together produce a good longterm prognosis in most patients with diffuse jejunoileitis.

Adolescent↗
PubMed1993

Antibodies to Mycobacterium paratuberculosis and nine species of environmental mycobacteria in Crohn's disease and control subjects.

Cultural and serological studies have provided limited, often conflicting, evidence of a role for mycobacteria in the pathogenesis of Crohn's disease. Interest has focussed on Mycobacterium paratuberculosis, previously considered to be common in the environment with no major role as a human pathogen. Whether a specific serum antibody response to mycobacteria occurs in Crohn's disease or ulcerative colitis was investigated. Sera from patients with Crohn's disease (n = 38), ulcerative colitis (n = 15), and a healthy control population (n = 30) were assayed in an enzyme linked immunosorbent assay (ELISA) using eight filtered sonicate mycobacterial preparations and a purified protein derivative made from the bovine tubercle bacillus. In addition, IgG, IgM, and IgA levels to M paratuberculosis were determined in sera from patients with active (n = 24) or inactive (n = 29) Crohn's disease and the control populations. There was strong evidence of contact with environmental mycobacteria in all patients and control populations, with the greatest responses to preparations of M avium, M tuberculosis, and M kansasii. A large proportion of patients with Crohn's disease had antibodies that bound most antigens tested but there were no statistical differences between these values and those of the control population. Similarly, there were no differences in antibody levels to M paratuberculosis in patient and control groups. Although a subset of patients with active Crohn's disease (25%) had IgG concentrations that exceeded the control mean by more than 2 SD, this phenomenon may not be specific to Crohn's disease: 20% of a small group of patients with coeliac disease had similarly raised IgG levels to M paratuberculosis. These findings do not provide serological evidence of a role for this organism in the pathogenesis of Crohn's disease.

Antibodies, Bacterial↗
PubMed1992

Mucosal cell-mediated immunity to mycobacterial, enterobacterial and other microbial antigens in inflammatory bowel disease.

Culture studies have suggested that Mycobacterium paratuberculosis may play a role in the aetiology of Crohn's disease. However, evidence of sensitization to mycobacterial antigens amongst patients with Crohn's disease has not yet been adequately demonstrated. Previous studies of cell-mediated immunity (CMI) in Crohn's disease were restricted to responses of peripheral blood mononuclear cells (PBMC) to mycobacterial antigens. In this study we have investigated the proliferative responses of both PBMC and mesenteric lymph node mononuclear cells (MLNMC) to a range of mycobacterial and non-mycobacterial antigens. There was no evidence of specific sensitization in the responses of MLNMC and PBMC from patients with inflammatory bowel disease (IBD) to the mycobacterial antigens. However, anergy to M. paratuberculosis could not be excluded. IBD MLNMC responses to most antigens were generally greater than those of PBMC, which were often undetectable. When compared with controls, there was evidence of increased CMI to a range of non-mycobacterial antigens, especially Yersinia enterocolitica, amongst both MLNMC and PBMC from patients with Crohn's disease and ulcerative colitis (UC). These results do not provide support to the proposed role of mycobacteria in the pathogenesis of Crohn's disease, but indicate that further investigation may determine a role for bacterial-specific T cell-mediated responses in the pathogenesis of IBD.

Antigens, Bacterial↗
PubMed1992

Sulphasalazine induced renal failure.

Two men with longstanding ulcerative colitis who were treated with sulphasalazine for several years and who developed chronic renal failure are reported. Renal biopsy specimens showed histological changes consistent with drug induced chronic intestinal nephritis. Extensive investigation made other causes of chronic renal failure unlikely. One of these patients underwent renal transplantation, the other has impaired but stable renal function.

Colitis, Ulcerative↗
PubMed1991

Strategy for management of distal ileal Crohn's disease.

We have determined the outcome of a defined policy for the management of distal ileal Crohn's disease using a prospective computer-based analysis of 139 patients diagnosed between 1970 and 1988 with a mean follow-up of 10 years. The policy in outline consists of conservative treatment for acute obstructive episodes, resection or strictureplasty for recurrent obstructive episodes, surgical treatment for abscess and fistula formation and specific medical treatment (corticosteroids, immunosuppressive therapy or metronidazole) for symptomatic non-obstructive disease. Twenty-nine patients had a benign course without resection. The remainder were treated surgically at some time but only 28 of these patients had specific treatment before operation. Thirty-three needed more than one resection and five needed more than three surgical procedures. Immediate, early or delayed surgical treatment did not affect the reoperation rates or the long-term outcome. Eleven patients died, ten of causes unrelated to Crohn's disease. Of the 128 living patients, 114 are fit and well, and only two are currently taking specific medication. Fourteen are unwell of whom six either need or have refused further surgery which could restore them to good health. This management policy has achieved excellent long-term results in nearly all patients, and our findings suggest that the timing of surgery and its nature are more important in determining outcome than specific medical therapy.

Adolescent↗
PubMed1991

Candidacidal activity of Crohn's disease neutrophils.

The ability of normal and Crohn's disease neutrophils to kill Candida albicans has been studied using neutrophils isolated from peripheral blood and suspended in phosphate buffered saline at 5 x 10(6) cells per ml. C albicans was grown to a stationary phase in broth culture and suspended in phosphate buffered saline at 10(7) organisms/ml. Neutrophils and Candida were then incubated together at 37 degrees C in a shaking water bath in the presence of fresh serum. At 30 and 60 minutes samples were withdrawn, neutrophils lysed, and Candida survival assessed by colony counting. Results were compared with control suspensions of Candida incubated with serum alone. After 30 and 60 minutes in the presence of autologous serum normal neutrophils had killed significantly more Candida than Crohn's disease neutrophils (mean (SD) 61.0 (16.7)% v 40.5 (16.2)% at 30 minutes, p less than 0.0001; 83.2 (7)% v 70.8) 16)% at 60 minutes, p less than 0.005). The results did not alter significantly when normal neutrophils were incubated with Candida in the presence of Crohn's disease serum instead of normal serum. When Crohn's disease neutrophils were incubated with Candida in the presence of normal serum instead of autologous serum there was some improvement in candidacidal ability at 30 minutes (48.9 (20.6)% v 40.5 (16.2)%, p less than 0.03) but not at 60 minutes. Phagocytosis, measured using a radiometric assay, was normal. Neutrophils from patients with Crohn's disease have an impaired ability to kill this granuloma provoking organism. It is not due to serum inhibitors or defective phagocytosis.

Adult↗
PubMed1991

Superoxide production by Crohn's disease neutrophils.

Neutrophil superoxide anion production was measured in healthy subjects and in patients with quiescent and active Crohn's disease using superoxide dismutase inhibitable cytochrome C reduction. Three stimuli were used: phorbol 12-myristate 13-acetate (PMA1), phorbol 20-oxo-20-deoxy 12-myristate 13-acetate (PMA2), and Candida albicans in serum. Normal neutrophils produced significantly more superoxide anion than Crohn's disease neutrophils with both PMA1 (mean (SD) 9.6 (2.2) v 8.6 (1.8) nmol/10(6) cells/5 minutes, p = 0.04) and PMA2 (1.8 (0.8) v 0.8 (0.77) nmol/10(6) cells/5 minutes, p = 0.00004). With C albicans in serum, normal and Crohn's disease neutrophils produced similar amounts of superoxide anion (4.4 (1.5) v 4.3 (1.7) nmol/10(6) cells/30 minutes, not significant). Results were independent of disease activity. Superoxide anion production by PMA-stimulated Crohn's disease neutrophils is significantly lower than by normal neutrophils.

Adult↗