Low mortality in ulcerative colitis and Crohn's disease in three regional centers in England.

OBJECTIVES: Recent epidemiological studies suggest that mortality rates for inflammatory bowel disease (IBD) are similar to those of the general population. However, most of this work has been done in referred populations or larger urban centers. We intended to estimate mortality rates for ulcerative colitis (UC) and Crohn's disease (CD) in three British district general hospital practices in Wolverhampton, Salisbury, and Swindon. METHODS: Consecutive patients with CD or UC were identified from 1978 to 1986 and followed prospectively. Demographic data, date and cause of death or health status at December 31, 1993 were used to estimate standardized mortality ratios (SMRs) and 95% confidence intervals. RESULTS: Sixty-four deaths occurred in 552 patients (UC 41 of 356; CD 23 of 196). The overall SMRs were 103 [95% confidence interval (CI): 79-140] for UC and 94 (95% CI: 59-140) for CD. The respective SMRs were higher only in the first year after diagnosis at 223 (95% CI: 99-439; p = 0.02) and 229 (74-535; p = 0.056), and even then, most subjects died from non-IBD causes (5 of 13). Nonsurvivors were significantly older than survivors in both UC and CD (p < 0.01). The SMR was also significantly greater during a severe first attack of UC at 310 (95% CI: 84-793; p = 0.04). Patients with perianal or colonic CD had an increased SMR [396 (95% CI: 108-335; p = 0.02) and 164 (95% CI: 82-335; p = 0.02)] respectively, partly related to the older mean age (52 vs 32 yr, p < 0.001). CONCLUSIONS: Mortality rates are not increased in IBD compared with the general population. However, older patients may be at increased risk of dying from other causes early in the disease clinical course.

Atrophy of the coeliac mucosa.

Details of 12 patients suffering from atrophy of the coeliac mucosa (ACM) are presented. These patients failed to respond to the elimination of gluten from their diets. Their jejunal biopsies were examined in detail with particular attention given to Paneth cell numbers, crypt length, mitotic rate and mucosal thickness. These biopsies were compared with the biopsies of responsive coeliac patients. The ACM patients were found to have a statistically significant reduction in Paneth cell numbers (P < 0.0005), reduced crypt length (P < 0.0125), reduced mitotic rate (P < 0.0005) and a thinner mucosa (P < 0.0005), when compared with the responsive coeliac group. In addition the ACM group had a lower albumin level compared with the responsive group (P < 0.0005). Most of the ACM patients responded when treated with oral corticosteroids. It is considered that the above features are markers of a non-responsive group of coeliac patients and thus might be useful for identifying those patients who may benefit from early treatment with oral corticosteroids if gluten withdrawal is not rapidly effective.

Sulphasalazine treatment and the colorectal mucosa-associated flora in ulcerative colitis.

AIM: To study the influence of sulphasalazine treatment on the mucosa-associated bacterial flora of rectal biopsy tissue specimens in patients with ulcerative colitis. PATIENTS: Twenty-four patients had newly diagnosed active ulcerative colitis; 20 patients had acute relapse of ulcerative colitis (10 not taking maintenance sulphasalazine); (40 patients had quiescent ulcerative colitis; 21 not taking maintenance sulphasalazine). The influence of 3 weeks of sulphasalazine treatment on the mucosa-associated flora was studied in the patients presenting with active disease. RESULTS: Comparison of patients according to sulphasalazine usage revealed few differences in the mucosal flora. In patients with quiescent ulcerative colitis, Escherichia coli was found at lower counts in patients taking maintenance sulphasalazine; however, this effect was not evident in patients with active disease. Inconsistent changes in other facultatives were seen between the two active disease groups, particularly for a miscellaneous group of unidentified Gram-positive rods. Three patients, all receiving sulphasalazine, were colonized with Clostridium difficile, but this did not appear to influence their disease. CONCLUSION: Sulphasalazine treatment in ulcerative colitis causes only minor disturbance to the populations of bacteria colonizing the colorectal mucosa.

Inflammatory bowel disease and domestic hygiene in infancy.

To test the hypothesis that Crohn's disease is caused by delayed exposure to enteric infections, we did a case-control study. We compared 133 patients who have Crohn's disease and 231 with ulcerative colitis who have controls selected from the general population and matched for age and sex. Crohn's disease was more common in subjects whose first houses had a hot-water tap (odds ratio 5.0, 95% CI 1.4-17.3) and separate bathroom (3.3, 1.3-8.3). Ulcerative colitis showed no clear relation to household amenities in infancy. These findings may explain why the incidence of Crohn's disease has increased in developed countries over the past 50 years.

Adhesive and hydrophobic properties of Escherichia coli from the rectal mucosa of patients with ulcerative colitis.

The adherent properties and hydrophobicity of Escherichia coli isolates have been compared from the rectal mucosa of patients with active and inactive ulcerative colitis and from a control patient group. Patients with active colitis were colonised less frequently and with lower numbers of E coli than were control patients. Mannose resistant adhesion to HEp-2 cells was determined for 124 isolates of E coli and surface hydrophobicity was estimated by salt agglutination in 96 of these isolates. There was no significant difference in the distribution of adherent strains between the colitis patient groups or with disease activity. E coli from the control patients were marginally less adhesive than those from colitics. The hydrophobicity of isolates did not differ significantly between colitic and control groups nor were there significant differences correlated with disease activity. Furthermore, for these mucosal E coli isolates, hydrophobicity and mannose resistant adhesion were unrelated characteristics.

The rectal mucosa-associated microflora in patients with ulcerative colitis.

The rectal mucosa-associated flora (MAF) of patients with ulcerative colitis has been studied in 25 patients with newly diagnosed disease, 20 with relapse of existing disease, and 44 who were in remission. Patients with active disease were re-examined twice during treatment. The MAF was simpler and less dense than the microflora of faeces. Obligate anaerobes usually predominated in the MAF although the ratio of obligate anaerobes to facultative species was lower than that found in faeces. Viable counts of the total flora and of its constituent genera varied considerably between patients. Counts of the total flora, of obligate anaerobes (including bifidobacteria, eubacteria and clostridia), and facultative organisms and micro-aerobes (enterobacteria and lactobacilli) were reduced in patients with active disease compared with those with inactive disease; corresponding carriage rates were also lower. Counts and carriage rates increased during treatment and approached those found in quiescent disease. The alterations in the MAF were especially marked in patients experiencing their first attack of ulcerative colitis. The relationship between these alterations and the aetiology and pathogenesis of this disease remains unclear.

Search for enteric microbial pathogens in patients with ulcerative colitis.

Microbial pathogens were sought in faeces of patients with active ulcerative colitis and again after 3 months treatment. 64 patients were examined during their first episode of ulcerative colitis and 30 with relapse of chronic disease. At presentation, bacterial pathogens were not found; 1 patient had cryptosporidiosis. In 10 patients treatment appeared to result in some loss of colonisation resistance as evidenced by colonisation with beta-haemolytic streptococci, Staphylococcus aureus, candida and Clostridium difficile. Unidentified cytotoxic activity was present in the faeces of 4 patients at presentation and 2 patients during or after treatment. We conclude that enteric infection is an uncommon finding in patients with active ulcerative colitis.

Comparison of cimetidine and pirenzepine in the healing and maintenance of remission in duodenal ulcer.

The effect of cimetidine and pirenzepine on the maintenance of healing in duodenal ulceration has been compared in a multi-centre, controlled study. One hundred and sixty-six patients with endoscopically proven duodenal ulceration have been randomised to receive either cimetidine 200 mg t.i.d. and 400 mg nocte, or pirenzepine 50 mg b.i.d. for 6 weeks. Patients in each group were well matched for age, sex, weight and cigarette, alcohol and antacid consumption. After 6 weeks significantly more cimetidine-treated patients had healed ulcers: cimetidine showed 8 unhealed out of 79, and pirenzepine 19 out of 74 (p = 0.01). The follow-up phase lasted for 52 weeks or until patient withdrawal or ulcer relapse. During the follow-up phase 77.6% of cimetidine-treated and 68.8% of pirenzepine-treated patients relapsed. This difference in relapse rates is not statistically significant (p = 0.23).

Comparison of 40 mg famotidine nightly and 150 mg ranitidine b.d.: ulcer healing and symptom relief in benign gastric ulcer.

Two hundred and eight patients with benign gastric ulcers seen on endoscopy were recruited by 13 hospitals in the United Kingdom and Ireland into this double-blind study. Patients were assigned by pre-randomized schedule to 8 weeks of treatment with either 40 mg famotidine at night or 150 mg ranitidine b.d. Repeat endoscopy confirmed complete ulcer healing in 62 of 77 evaluable patients in the famotidine group (81%) and 58 of 71 in the ranitidine group (82%). The treatments were equally effective in promptly relieving day and night pain. Adverse events were uncommon; dizziness and headaches were the most frequently reported in both groups. In conclusion, night-time famotidine is as effective as twice daily ranitidine in healing benign gastric ulcers and provides similarly rapid symptomatic relief.

An unusual metabolic myopathy: a malate-aspartate shuttle defect.

Studies on a 27-year-old man with a 3-year history of exercise-induced muscle pain, passage of red urine and elevated serum creatine kinase are described. Histological examination of a biopsy from quadriceps revealed non-specific myopathic changes with occasional clusters of subsarcolemmal mitochondria. The phosphorylase stain was normal. Phosphorous nuclear magnetic resonance (NMR) spectroscopy studies of gastrocnemius and flexor digitorum superficialis muscles showed no abnormalities at rest. During aerobic exercise there was an abnormally rapid decrease in phosphocreatine concentration but the pH remained within the normal range. There was a build-up of phosphomonoester (probably glucose 6-phosphate), usually indicative of a block in glycolysis. However, a primary defect in the glycolytic pathway seemed unlikely because muscle acidified normally during ischaemic exercise. Recovery from exercise was unusual in that phosphocreatine resynthesis and inorganic phosphate disappearance followed similar prolonged time courses (in control subjects the rate of inorganic phosphate disappearance was about twice as fast as the rate of phosphocreatine resynthesis). The transport of inorganic phosphate into the mitochondria appeared to be delayed. These slow recovery data suggested that oxidative metabolism was impaired. However, with all substrates tested, isolated muscle mitochondria had rates of oxygen uptake that were similar to control values, thereby ruling out a primary defect in mitochondrial respiration. A system involving several mitochondrial transport systems, the malate-aspartate shuttle, was measured. The activity in the patient's isolated mitochondria was less than 20% of the activity present in samples from control subjects. This patient is the only one so far reported with a defect involving the malate-aspartate shuttle system.

Comparative trial of sodium cromoglycate enemas with prednisolone enemas in the treatment of ulcerative colitis.

A double blind multicentre study comparing sodium cromoglycate (600 mg/100 ml) by enema with prednisolone (20 mg/100 ml) by enema is reported. The study was conducted over a nine week period in the treatment of 70 patients with ulcerative colitis. Analysis of symptoms showed significant decreases in scores for patients in both groups, both at four and eight weeks; the only difference between the two groups was a significantly greater improvement in the reduction of rectal bleeding after four weeks in the prednisolone group. On sigmoidoscopy, both treatment groups showed a highly significant improvement after four and eight weeks with no significant differences being seen between the groups. Histology of the rectal biopsies showed a significant improvement in the inflammation of the mucosa for both treatment groups after four and eight weeks with no differences being observed between the groups. There were no significant changes in eosinophils from baseline and no difference between the groups at four and eight weeks.

A double-blind controlled trial of the effect of sodium cromoglycate in preventing relapse in ulcerative colitis.

A double-blind controlled trial of the effect of sodium cromoglycate (SCG) in preventing relapse in ulcerative colitis has been completed in 100 subjects. In patients already taking sulphasalazine, SCG did not prove to be of any additional benefit. However, in patients not on any other maintenance therapy, the relapse rate was 40% for SCG as compared with 75% for placebo. A large study of the effect of SCG in patients intolerant of sulphasalazine is indicated.

Gastro-cutaneous fistula following anterior gastropexy.

Two patients are described who developed a gastric fistula to the anterior abdominal wall following anterior gastropexy. Both fistulae closed spontaneously without any specific treatment. It is suggested that the fixation of the stomach to the anterior abdominal wall allows the fistula to discharge externally thus preventing peritoneal contamination with its serious consequences.

Management of upper gastrointestinal haemorrhage.

The results of emergency endoscopy in 61 patients with upper gastrointestinal haemorrhage are presented. The merits of urgent endoscopy in tha management of this condition are discussed and the results obtained compared with those of other methods of investigation.

Atopic disorders and adult coeliac disease.

A history of asthma, hay fever, and flexural eczema was significantly more common in patients with adult coeliac disease (A.C.D.) than in normal controls. Autoantibodies were also more common in A.C.D. First-degree relatives of A.C.D. patients were more likely than controls to have atopic disorders. A deficiency of local mucosal immunity due to abnormal IgA responses may underly this association between A.C.D. and atopy.