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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
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↗
PubMed1989

Prognosis after surgery for colonic Crohn's disease.

The long-term prognosis including operation rates, the incidences of recurrent disease, morbidity and mortality and current status has been analysed in a group of 360 patients with Crohn's colitis grouped according to the primary site of macroscopic disease at diagnosis. The group has been followed from diagnosis for a mean period of 14.9 years. The overall operation rate was 76 per cent. Prolonged spontaneous or drug induced remission occurred at all sites: right-sided disease (11 per cent), extensive colonic disease (21 per cent) and left-sided disease (38 per cent). The cumulative reoperation rates at 5 and 10 years after right hemicolectomy were 26 and 46 per cent, after colectomy and ileorectal anastomosis 46 and 60 per cent, and after panproctocolectomy 10 and 21 per cent, respectively. There was a twofold excess mortality rate from related Crohn's disease deaths during the period of review, but the mortality rate has fallen with time. There have only been 11 related deaths in the last decade, of which eight were probably unavoidable. The current status of most patients is good, although treatment has included a permanent stoma in less than half (41 per cent) the patients still under review. Currently all but 14 patients are well and symptom-free and only 16 are receiving specific medical treatment. Until the aetiology of Crohn's colitis is understood, if medical treatment has failed to resolve symptoms, appropriate surgical treatment in experienced hands is an effective way of restoring patients with chronic persistent symptoms to good health.

Adolescent↗
PubMed1989

Employment prospects for patients with intestinal stomas: the attitude of occupational physicians.

The attitude of 126 occupational physicians to the employment problems of patients with intestinal stomas were assessed by a postal questionnaire. Heavy work and work in hot places were commonly (65 and 49 per cent of respondents respectively) considered 'unsuitable'. Work as a food handler, handling toxic chemicals and driving duties was thought to be 'unsuitable' by 35, 14 and 10 per cent of respondents respectively and actually forbidden by a few physicians. Risk of spread of infection was perceived to be greater than normal for someone with a stoma by 28 per cent of respondents. This attitude was significantly more common (p less than 0.05 Chi square) among the associate members compared to full members of the Faculty of Occupational Medicine. Attitudes to people with either an ileostomy or a colostomy were similar. Most respondents (87 per cent) expected more sickness absences than normal for people with inflammatory bowel disease without a stoma but half appreciated that the creation of a stoma would result in normal amounts of sickness absence. The Occupational Physicians' views of which jobs within their industry were unsuitable for stoma patients were inconsistent. In practice most tasks can be performed normally by someone with a stoma so that each case should be assessed on an individual basis. There is a need for greater understanding and awareness by doctors of the good employment potential of people with intestinal stomas. The reasons for present attitudes are reviewed and new guidelines suggested.

Absenteeism↗
PubMed1989

Malignancy in coeliac disease--effect of a gluten free diet.

Two hundred and ten patients with coeliac disease previously reported from this unit were reviewed at the end of 1985 after a further 11 years of follow up. The initial review at the end of 1974 could not demonstrate that a gluten free diet (GFD) prevented these complications, probably because the time on diet was relatively short. The same series has therefore been kept under surveillance with the particular aim of assessing the effects of diet on malignancy after a further prolonged follow up period. Twelve new cancers have occurred: of which one was a carcinoma of the oesophagus and two lymphomas. Thirty nine cancers developed in 38 patients and of 69 deaths, 33 were the result of malignancy. A two-fold relative risk (RR) of cancer was found and was because of an increased risk of cancer of the mouth and pharynx (RR = 9.7, p less than 0.01, 95% confidence interval (CI) = 2.0-28.3), oesophagus (RR = 12.3, p less than 0.01, CI = 2.5-36.5), and of non-Hodgkin's lymphoma (RR = 42.7, p less than 0.001, CI = 19.6-81.4). The results indicate that for coeliac patients who have taken a GFD for five years or more the risk of developing cancer over all sites is not increased when compared with the general population. The risk is increased, however, in those taking a reduced gluten, or a normal diet, with an excess of cancers of the mouth, pharynx and oesophagus (RR = 22.7, p < 0.001), and also of lymphoma (RR = 77.8, p < 0.001). A significant decreasing trend in the excess morbidity rate over increasing use of a GFD was found. The results are suggestive of a protective role for a GFD against malignancy in coeliac disease and give further support for advising all patients to adhere to a strict GFD for life.

Celiac Disease↗
PubMed1989

Plasma fibronectin in Crohn's disease.

The hypothesis that abnormal fibronectin metabolism in Crohn's disease could be an important mechanism leading to stricture formation or postoperative infection was tested in three related studies. (1) Lower concentrations of plasma fibronectin (p less than 0.05) were found in 20 patients with small and large bowel Crohn's disease (mean 0.24 g/l) compared with 13 patients with more limited disease confined to only small or only large bowel (mean 0.27 g/l) or 20 healthy controls (mean 0.29 g/l). (2) In 25 patients followed for 10 days after operation for Crohn's disease, there was a significant fall in fibronectin concentrations of 43% (p less than 0.01, Wilcoxon's rank-sum test). This fall was maximal on the second postoperative day and was more marked in patients undergoing more major operative procedures. (3) The predictive value of plasma fibronectin for subsequent stricture formation or progression was studied for one year; during which 10 patients developed strictures requiring operative treatment. Higher plasma fibronectin concentrations were related to stricture formation, although there was not a complete, predictive relationship. In this study we found that plasma fibronectin concentrations were low in patients with extensive or severe Crohn's disease, fall after operation and may be related to the risk of stricture formation. This relationship is unlikely to be of clinical value, although it shows the potential significance of fibronectin in the pathogenesis of strictures.

Adult↗
PubMed1989

Mortality in Crohn's disease--a clinical analysis.

We have examined the causes of death and the changing pattern of mortality over time among 769 patients with Crohn's disease under long-term review between 1944 and 1984. One hundred and fifty-six patients have died. The cause of death could not be classified in five. The deaths were divided into those related directly to Crohn's disease and unrelated deaths from incidental causes. The cause and age at death among 59 unrelated deaths was similar to that expected in the general population. The common causes of related deaths were sepsis, digestive tract cancer, pulmonary embolus and metabolic disorders. There were 30 deaths after surgery, usually from sepsis after emergency surgical treatment. There have been fewer deaths in recent years and the cause of death has altered. Sepsis and electrolyte imbalance have declined in importance and cancer of the digestive tract is now the most common cause of related death. Occasional death from sepsis occurs in elderly patients. Elective rather than emergency surgical treatment and the routine use of antimicrobial prophylaxis before surgery has probably reduced mortality. With the exception of cancer of the digestive tract the appropriate medical and surgical treatment of patients with Crohn's disease can eliminate excess mortality previously associated with the disorder.

Adolescent↗
PubMed1989

Enterovesical fistulas in Crohn's disease.

A total of 19 enterovesical fistulas were recorded in a series of 799 patients with Crohn's disease (2.4%). The origin of the fistulas was: ileum (9), colon (6) and four were complex involving the small and large bowel. Only 13 patients presented with urinary symptoms: pneumaturia (9), haematuria (1) and urinary tract infection (3). Four fistulas were identified incidentally during contrast radiology, one fistula was identified during a laparotomy and one further fistula developed after a previous resection for Crohn's disease. Four patients were managed conservatively and all are asymptomatic, but it is not known whether the fistula has healed. Twelve fistulas were resected: 9 healed, 2 recurred and 1 patient died following resection for a malignant fistula complicating Crohn's disease. Early in the series three patients were managed by bypass or defunction of the fistula. In all cases the sepsis persisted resulting in mortality. Persistent symptomatic fistulas should be treated by resection of the affected segment of bowel with primary anastomosis if appropriate. The defect in the bladder should be closed over an indwelling catheter which should not be removed until there is radiological confirmation that the bladder defect has healed satisfactorily.

Adolescent↗
PubMed1988

Natural history and treatment of anorectal strictures complicating Crohn's disease.

Forty-four patients seen between 1975 and 1985 with anorectal strictures complicating Crohn's disease have been reviewed to determine the natural history and outcome of surgical treatment. Proctitis was present in 98 per cent, and 93 per cent of patients had sever perianal disease. The site of strictures was rectal in 22, anal in 15 and anorectal in 11 (4 patients had a stricture at 2 sites). Initial treatment was by rectal excision alone in 6, dilatation in 33, and 5 needed no treatment at all. Single dilatation was effective in 15, 8 required two dilatations and in 10 repeated dilatation was necessary. Proctocolectomy was eventually required in 19 patients, 2 have a loop ileostomy and 1 has an ileostomy with a rectal stump in situ. Only 21 remain asymptomatic while 3 continue to need dilatation. Perineal wound healing was delayed in 9 of 19 patients having a proctocolectomy and in 3 the perineal wound has never healed.

Adolescent↗