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Six patients with short intestine (jejunal length 25-70 cm) on long-term parenteral nutrition, needing 4-5 L of intravenous fluid daily, were given octreotide (a somatostatin analogue, SMS 201-995) to investigate whether it would reduce beneficially their secretory diarrhoea (3.6-6.9 kg/day). They consumed the same diet for 2 control days, followed by 2 test days. Octreotide was given intravenously, initially in a dose of 50 micrograms b.d. through the central feeding line. There was a significant reduction of daily stomal output (0.5-5.0 kg) and daily sodium and potassium output; however there was no significant change in energy absorption. The response to octreotide was greatest in those patients who absorbed least nutrients. A dose increase to 100 micrograms t.d.s. gave no further measurable benefit though the patients found it smoothed-out the post-prandial rise in stomal output. Two patients were continued on long-term octreotide therapy, which allowed for a daily reduction in intravenous fluid of 1 and 1.5 L. Octreotide's anti-secretory effect was found to have been maintained when it was retested in one patient after a year of continuous therapy.

The efficacy of two doses of balsalazide for the maintenance of remission in patients with ulcerative colitis was compared in a double-blind multicentre trial. Sixty-five patients received a 2 g daily dose, and 68 a 4 g dose. The patient groups were similar at entry for sex, age, and disease distribution. Clinical assessment was carried out at 3-monthly intervals, with sigmoidoscopy, rectal biopsy, and blood tests on entry and at 26 and 52 weeks. Clinical relapse over twelve months was significantly less common on the 4 g dose (36%), than on the 2 g dose (55%), P less than 0.01. There were eight withdrawals on 2 g daily and 13 on 4 g daily, six and nine respectively being mainly due to gastrointestinal intolerance. It is concluded that balsalazide is a well-tolerated drug, and is effective for the maintenance of remission in patients with ulcerative colitis, the optimal dose being greater than 2 g daily.

Inflammatory bowel disease (IBD) is a multifactorial disorder, with both genetic and environmental factors contributing to the two clinical phenotypes of Crohn's disease (CD) and ulcerative colitis (UC). The underlying genetic model is thought to involve multiple genes with complex interactions between disease loci, and the NOD2 gene on chromosome 16 has recently been identified as a CD susceptibility locus. Several genome-wide linkage studies have identified candidate regions, but there has been little replication across studies. Here we investigate the role of sex-specific loci in susceptibility to IBD. Linkage data from our previously reported genome search and follow-up study were stratified by the sex of the affected sib pair. Non-parametric linkage analysis was performed using Genehunter Plus. Simulation studies were used to assess the significance of differences in LOD scores between male and female families for each chromosome. Several regions of sex-specific linkage were identified, including existing and novel candidate loci. The major histocompatibility region on chromosome 6p, referred to as IBD3, showed evidence of male-specific linkage with a maximum LOD score of 5.9 in both CD and UC male-affected families. Regions on chromosomes 11, 14 and 18 showed strong evidence of linkage in male-affected families but not in female-affected families. No evidence of sex-specific linkage was found in the IBD1 or IBD2 candidate regions of chromosomes 16 and 12. The existence of sex-specific linkage is further evidence of the complex mechanisms involved in IBD and will facilitate future studies to identify susceptibility genes.

BACKGROUND AND AIMS—Genetic predisposition for inflammatory bowel disease (IBD) has been demonstrated by epidemiological and genetic linkage studies. Genetic linkage of IBD to chromosome 3 has been observed previously. A high density analysis of chromosome 3p was performed to confirm prior linkages and elucidate potential genetic associations. METHODS—Forty three microsatellite markers on chromosome 3 were genotyped in 353 affected sibling pairs of North European Caucasian extraction (average marker density 2 cM in the linkage interval). Marker order was defined by genetic and radiation hybrid techniques. RESULTS—The maximum single point logarithm of odds (LOD) score was observed for Crohn's disease at D3S3591. Peak multipoint LOD scores of 1.65 and 1.40 for the IBD phenotype were observed near D3S1304 (distal 3p) and near D3S1283 in the linkage region previously reported. Crohn's disease contributed predominantly to the linkage. The transmission disequilibrium test showed significant evidence of association (p=0.009) between allele 4 of D3S1076 and the IBD phenotype (51 transmitted v 28 non-transmitted). Two known polymorphisms in the CCR2 and CCR5 genes were analysed, neither of which showed significant association with IBD. Additional haplotype associations were observed in the vicinity of D3S1076. CONCLUSIONS—This study provides confirmatory linkage evidence for an IBD susceptibility locus on chromosome 3p and suggests that CCR2 and CCR5 are unlikely to be major susceptibility loci for IBD. The association findings in this region warrant further investigation. Keywords: inflammatory bowel disease; fine mapping; chromosome 3

Inflammatory bowel disease (IBD) is characterized by a chronic relapsing intestinal inflammation. IBD is subdivided into Crohn disease and ulcerative colitis phenotypes. Given the immunologic dysregulation in IBD, the human-leukocyte-antigen region on chromosome 6p is of significant interest. Previous association and linkage analysis has provided conflicting evidence as to the existence of an IBD-susceptibility locus in this region. Here we report on a two-stage linkage and association analysis of both a basic population of 353 affected sibling pairs (ASPs) and an extension of this population to 428 white ASPs of northern European extraction. Twenty-eight microsatellite markers on chromosome 6 were genotyped. A peak multipoint LOD score of 4.2 was observed, at D6S461, for the IBD phenotype. A transmission/disequilibrium test (TDT) result of P=.006 was detected for D6S426 in the basic population and was confirmed in the extended cohort (P=.004; 97 vs. 56 transmissions). The subphenotypes of Crohn disease, ulcerative colitis, and mixed IBD contributed equally to this linkage, suggesting a general role for the chromosome 6 locus in IBD. Analysis of five single-nucleotide polymorphisms in the TNFA and LTA genes did not reveal evidence for association of these important candidate genes with IBD. In summary, we provide firm linkage evidence for an IBD-susceptibility locus on chromosome 6p and demonstrate that TNFA and LTA are unlikely to be susceptibility loci for IBD.

Objective:To compare the methods used for diagnosis and the clinical features of non-specific inflammatory bowel disease (IBD) in the north and south of Europe.Design:A prospective study over 2 years in 1991-3 at eight centres in the north and 12 in the south of Europe, using the same criteria for d

Training to contract the abdominal muscles effectively and to relax the pelvic floor during defecation straining helps some patients with severe constipation. Hitherto all such training has used a visible or audible signal of sphincter muscle activity as a biofeedback method to assist in relaxation. A randomised controlled trial comparing the outcome of muscular training without any biofeedback device with the same training supplemented by an electromyographic (EMG) record visible to the patient is reported. Significant symptomatic improvement was noted and electromyographic measurements confirmed a decrease in pelvic floor muscle activity during defecation straining after treatment in both groups. The outcome was similar in the two treatment groups. Muscular coordination training using personal instruction and encouragement without a visual display is thus a potentially successful treatment suitable for outpatient use by paramedical personnel.

Background/Aims: Antineutrophil cytoplasmic antibodies have been reported to occur more frequently in healthy first-degree relatives of patients with ulcerative colitis than in healthy controls. The aim of this study was to determine their prevalence in families in which more than one member was affected with inflammatory bowel disease. Methods: With use of an indirect immunofluorescence method, 168 affected members and 197 unaffected first-degree relatives in 56 such families were studied. Results: Antibodies were detected in 46% of patients with ulcerative colitis without a positive family history and in 44% of those within families with several affected members. There was no evidence of clustering of antibodies in particular families. Within families in which both ulcerative colitis and Crohn's disease coexisted, antibodies were detected primarily in patients with ulcerative colitis. Antibodies were seldom present (3%) in those patients with Crohn's disease, whether they were familial or nonfamilial cases. Similarly, antibodies were seldom present (3%) in controls or the unaffected first-degree relatives of patients with inflammatory bowel disease. Conclusions: Antineutrophil cytoplasmic antibodies are associated with ulcerative colitis, and their presence is not increased in the first-degree relatives of patients with ulcerative colitis. They are more likely to be a consequence of the disease than a subclinical genetic disease marker.

Background/Aims: Cancer surveillance in patients with ulcerative colitis is of unproven benefit. This study assesses the efficacy and analyzes factors limiting the success of a surveillance program during a 21-year period in 332 patients with ulcerative colitis to the hepatic flexure and disease duration exceeding 10 years. Methods: Clinical assessment and sigmoidoscopy with biopsy was undertaken yearly. Colonoscopy and biopsy every 10 cm throughout the colon was performed every 2 years or more often if dysplasia was found. Only biopsy specimens reported as showing dysplasia were reviewed. Results: Surveillance contributed to detection of 11 symptomless carcinomas (8 Dukes A, 1 Dukes B, and 2 Dukes C), but 6 symptomatic tumors (4 Dukes C and 2 disseminated) presented 10–43 months after a negative colonoscopy. Dysplasia without carcinoma was confirmed in 12 symptomless patients who underwent colectomy. The 5-year predictive value of low-grade dysplasia for either cancer or highgrade dysplasia was 54% using current criteria. Conclusions: Surveillance identified some patients at a curable stage of cancer or with dysplasia. Limiting factors were failure to include patients with presumed distal colitis, biennial colonoscopy, the number of biopsy specimens at each colonoscopy, and variation in histological identification and grading of dysplasia.

This study examined three features associated with colorectal carcinoma complicating ulcerative colitis: (a) the distribution of 157 cancers in 120 patients with ulcerative colitis treated at St Mark's Hospital between 1947 and 1992; (b) the frequency at which dysplasia was found at a distance from the tumour in 50 total proctocolectomy specimens in which an average of 27 histology blocks were reviewed, and (c) the five year survival rate according to Dukes's stage and participation in a surveillance programme. Of 157 carcinomas, 88 (56%) occurred in the rectosigmoid, 19 (12%) in the descending colon or splenic flexure, and 50 (32%) in the proximal colon. Among the 120 patients, the rectum or sigmoid colon contained cancer in 81 (67.5%). Dysplasia was detected in 41 of 50 reviewed proctocolectomy specimens (82%). Dysplasia distant to a malignancy occurred in 37 (74%); two were classified indefinite, probably positive, 19 were low grade, and 16 were high grade; in 18 specimens there was an elevated dysplastic lesion. Survival was related to the Dukes's stage: about 90% of patients with Dukes's A or B cancer were alive at five years. The five year survival of 16 patients in whom cancer developed during surveillance was 87% compared with 55% of 104 patients who did not participate in surveillance (p = 0.024).

Objective To determine the role of oral cyclosporin in the management of patients with chronic active Crohn's disease. Design Double-blind, placebo-controlled study of oral cyclosporin (5 mg/kg) versus placebo in combination with prednisolone over an initial period of 3 months. Patients The trial included 147 patients with chronic active Crohn's disease. Criteria for entry were as follows: patients with active disease requiring ≥10 mg prednisolone daily and/or azathioprine to control symptoms, and patients relapsing within 4 weeks of finishing one of these treatments. No case record form was completed for one patient. The data were analysed on an intention-to-treat basis for 146 patients. Outcome measures Clinical response was defined as the resolution of symptoms or a significant improvement on withdrawal or reduction of prednisolone. Disease activity was also assessed by the Harvey-Bradshaw Activity Index and laboratory indicators of activity (erythrocyte sedimentation rate, C-reactive protein). Results No significant differences were observed between the two groups with respect to clinical outcome, corticosteroid dosage required, or changes in the indices of activity over the 3-month trial period. Adverse reactions in the cyclosporin-treated patients were not uncommon, but none were serious or prolonged. Conclusion This trial does not support the value of oral cyclosporin (5 mg/kg) for the management of chronic active Crohn's disease.

The incidence of various cancers, especially non-Hodgkin lymphoma (NHL), is higher among patients who receive azathioprine for immunosuppression after organ transplants than in the general population. We have studied the risk of neoplasia after azathioprine in 755 patients treated for inflammatory bowel disease. The patients received 2 mg/kg daily for a median of 12.5 months (range 2 days to 15 years) between 1962 and 1991; median follow-up was 9 years (range 2 weeks to 29 years). Overall there was no significant excess of cancer: 31 azathioprine-treated patients developed cancer before age 85 compared with 24.3 expected from rates in the general population (observed/expected ratio 1.27, p = 0.186). There was a difference in the frequency of colorectal (13) and anal (2) carcinomas (expected 2.27; ratio 6.7, p = 0.00001); these tumours are recognised complications of chronic inflammatory bowel disease. There were 2 cases of invasive cervical cancer (expected 0.5), but no case of NHL. Among patients with extensive chronic ulcerative colitis there was no difference in cancer frequency between 86 who had received azathioprine and 180 matched patients who had never received it. Thus, azathioprine treatment does not substantially increase the risk of cancer in inflammatory bowel disease.

Objective: To assess biofeedback training as treatment in a consecutive series of patients with idiopathic constipation. Design: Symptomatic and physiological assessment before and after treatment. Methods: Assessment included a record of symptoms by diary card, measurement of whole gut transit time, defecation proctography and anorectal function tests. During training sessions, muscular activity of the pelvic floor was displayed to the patient as an electromyographic trace. The patient was taught to recognize resting electrical activity and the increase associated with voluntary contraction of the pelvic floor. If there was an increase (rather than the normal decrease) in activity during defecation straining, the patient was encouraged to strain while maintaining relaxation of the anal sphincter muscles. Patients were assessed at the end of treatment, after 6 weeks and after 6-12 months

Patients with ulcerative colitis (UC) are at increased risk of colorectal carcinoma.1,2 Many clinicians practice colonoscopic surveillance in these patients in the hope of detecting dysplasia or an early cancer at a surgically curable stage. However, a recent audit of gastroenterologists showed such surveillance to be disorganised and inconsistent.3 Much debate surrounds the efficacy and cost effectiveness of surveillance programmes in UC4–6 because they were introduced without benefit of randomised controlled trials. The following guidelines should bring uniformity to the process and be of help to both surgeons and physicians. The colorectal cancer risk in patients with colonic Crohn’s disease is similar to that in UC7,8 and thus the guidelines for UC should be equally applicable to such patients with Crohn’s disease. 1. Surveillance colonoscopies should be performed when the disease is in remission. (Recommendation Grade: C). 2. All patients should have a screening colonoscopy after 8–10 years that will also clarify disease extent. (Recommendation Grade: C). 3. Regular surveillance should begin after 8–10 years (from onset of symptoms) for pancolitis and after 15–20 years for left sided disease. (Recommendation Grade: C). 4. As the risk of cancer increases exponentially with time, there should be a decrease in the screening interval with increasing disease duration. For patients with pancolitis, in the second decade of disease a colonoscopy should be conducted every three years, every two years in the third decade, and yearly by the fourth decade of disease. (Recommendation Grade: C). 5. Two to four random biopsy specimens every 10 cm from the entire colon should be taken with additional samples of suspicious areas. (Recommendation Grade: C). Patients with primary sclerosing cholangitis (including those with an orthotopic liver transplant) represent a subgroup at higher risk of cancer and they should have annual colonoscopy. (Recommendation Grade: C). Although it …

Myelosuppression is an important and potentially lethal complication of azathioprine treatment. The blood count has been reviewed in all patients treated with azathioprine for inflammatory bowel disease over 27 years in one hospital. Altogether 739 patients (422 with Crohn's disease, 284 with ulcerative colitis, and 33 with indeterminate colitis) were treated with 2 mg/kg/day azathioprine for a median of 12.5 months (range 0.5-132) between 1964 and 1991. Full blood counts were performed monthly for the duration of treatment. In 37 patients (5%) who developed bone marrow toxicity, the drug was withdrawn or the dose reduced. Thirty two of these patients were asymptomatic and five developed symptoms. Leucopenia (white blood count less than 3.0 x 10g/l) occurred in 28 (3.8%) patients, in nine of whom it was severe (white blood count < 2.0 x 10(9)/l). Of these nine patients, three were pancytopenic: two died from sepsis and the other had pneumonia but recovered. A further two patients with severe leucopenia developed a mild upper respiratory infection only. Thrombocytopenia (platelet count < 100,000 x 10(6)/l) in 15 patients was associated with leucopenia in six and developed in isolation in a further nine (total 2%). Isolated thrombocytopenia was never clinically severe. Myelotoxicity from azathioprine developed at any time during drug treatment (range 2 weeks-11 years after starting the drug) and occurred either suddenly or over several months. Bone marrow suppression as a result of azathioprine treatment is uncommon when a moderate dose is used, but is potentially severe. Leucopenia is the commonest and most important haematological complication. Regular monitoring of the full blood count is recommended during treatment.

Preparations of the circular muscle layer from the sigmoid colon resected from patients with idiopathic chronic constipation were compared, at an electrophysiological level using the sucrose-gap technique, with preparations of the same region of the intestine resected from patients with rectal carcinoma. Non-adrenergic, non-cholinergic inhibitory neuromuscular transmission, represented by inhibitory junction potentials, was present in preparations from both groups. However, the inhibitory response in preparations from constipated patients had a slower or longer time-course than in those from cancer patients. Also, rebound activity following inhibitory transmission was observed in 34% of preparations from constipated patients but was observed in 67% of preparations from cancer patients. Preparations from both groups displayed the same patterns of spontaneous activity and the same proportion of each group was quiescent. The threshold for generation of action potentials and the passive resistance of the smooth muscle membrane were the same in both groups. However, quiescent preparations from constipated patients were less likely to discharge trains of action potentials when the smooth muscle membrane was depolarized than were preparations from cancer patients. These changes in transmission processes and excitability in tissue from constipated patients are discussed in relation to altered states of colonic motility found in people with idiopathic chronic constipation.

Adult patients with an idiopathic megarectum or megacolon can experience severe constipation requiring surgical treatment. Some of these patients have a proximal colon of normal diameter, with dilatation involving only the left or distal colon and rectum. The results of partial colonic and rectal resection with coloanal anastomosis in such patients have been reviewed. Seven patients (two female and five male) underwent a coloanal anastomosis over a seven-year period. The median age at operation was 19 years, the mean age at onset of symptoms was five years, and the mean follow-up period was one year. Five patients experienced a return to normal bowel frequency with the loss of most symptoms. One patient has an ileostomy because of persistent constipation after the procedure. One subject died because of postoperative bleeding from the anastomosis and subsequent cardiac and respiratory complications. This operation may have a place in the treatment of severe constipation caused by idiopathic megarectum and megacolon, but careful preoperative motility studies and meticulous attention to operative technique are required for a good outcome.

Patients with severe idiopathic constipation are almost exclusively women of reproductive age. To investigate the possibility of a sex hormone abnormality in this condition, we have compared a range of sex hormones during the follicular and luteal phases of the menstrual cycle in 23 healthy women (mean age 33 years) with those in 26 patients with severe idiopathic constipation (mean age 32 years, spontaneous bowel frequency less than one per week). In the patients there was a reduction in the follicular phase of progesterone (4.5 v 4 nmol/l, p = 0.006, median value, controls v patients), 17 hydroxyprogesterone (9.7 v 5.8 nmol/l, p = 0.01), cortisol (387 v 245 nmol/l, p = 0.008), testosterone (2.3 v 1.8 nmol/l, p less than 0.001), androstenedione (10.3 v 8.4 nmol/l, p = 0.02), and dehydroepiandrosterone sulphate (5.1 v 3.0 mumol/l, p = 0.03). In the luteal phase there was a reduction of oestradiol (483 v 350 pmol/l, p = 0.015), cortisol (322 v 242 nmol/l, p = 0.047), and testosterone (2.4 v 1.7 nmol/l, p = 0.003). The concentrations of sex hormone binding globulin, prolactin, luteinising hormone, and follicle stimulating hormone were not significantly different in either phase of the cycle. Women with severe idiopathic constipation have a consistent reduction in steroid hormones.

24 h oral intake and intestinal output were studied in 15 patients with a short residual length of jejunum and no colon. 8 patients showed a net secretory, and 7 a net absorptive response to food. In secretors, daily intestinal output exceeded oral intake (mean 2.3 kg wet weight, and 233 mmol sodium). Long-term parenteral fluid and electrolyte replacements were needed only in those with a secretory response. Jejunal length inversely correlated with net intestinal output of fluid, sodium, potassium, and with percentage energy absorption. A secretory response was observed if jejunal length was less than 100 cm and was reduced by gastric antisecretory drugs and octreotide.

Nine patients with short bowel syndrome and high intestinal output received octreotide either intravenously (50-100 micrograms t.i.d.) or subcutaneously (100 micrograms b.i.d.) on 2 test days. In the 6 patients with net secretory output, there was a reduction in mean daily intestinal output of 0.5-5.0 kg; total daily intestinal output of sodium and potassium was also reduced significantly. Of the 3 patients with a net absorptive state, there was a worsening of output in 2 and no improvement occurred in the other. Two patients with net secretory output received long-term octreotide therapy, allowing a reduction in daily intravenous fluid intake of 1.0-1.5 litres.

Objective : The normal adult human small intestinal length, measured surgically or at autopsy from the duodeno-jejunal flexure, ranges from 275 to 850cm. The length is generally shorter in women than in men. Patients with a short bowel have often had relatively little bowel resected and the majority of patients are women. We aimed to determine whether patients with a short bowel had a short small intestinal length before any resections. Patients and methods : In 11 patients (six men and five women) with Crohn's disease and less than 200cm residual small intestine, both the residual length of small intestine and the amount resected were measured. Results : Patients had a median of four resections (range 1-5). The median length of small bowel resected was 120 cm (range 60-165cm) and the medium length of small bowel remaining was 125 cm (range 90-185 cm). Thus, the calculated median original small intestinal length was 240 cm (range 205-315 cm). Conclusion : Although there may have been some bowel shortening as a result of Crohn's disease, the original small intestinal length before any resections was short. It is therefore more important, after performing a bowel resection, to measure the remaining than the resected bowel length. Patients with Crohn's disease and a short bowel may have had a short but 'normal' small intestinal length before any bowel was resected.

Background Genetic predisposition to inflammatory bowel disease (IBD) has been shown by epidemiological and linkage studies. Genetic linkage of IBD to chromosome 16 has been previously observed and replicated in independent populations. The recently identified NOD2 gene is a good positional and functional candidate gene since it is located in the region of linkage on chromosome 16q12, and activates nuclear factor (NF) kappaB in response to bacterial lipopolysaccharides. Methods We sequenced the coding region of the NOD2 gene and genotyped an insertion polymorphism affecting the leucine-rich region of the protein product in 512 individuals with IBD from 309 German or British families, 369 German trios (ie, German patients with sporadic IBD and their unaffected parents), and 272 normal controls. We then tested for association with Crohn's disease and ulcerative colitis. Findings Family-based association analyses were consistently positive in 95 British and 99 German affected sibling pairs with Crohn's disease (combined p

Corticosteroid or 5-aminosalicylic acid enemas are the treatment of choice for distal ulcerative colitis but up to one third of patients may be unresponsive. As an alternative therapy might be advantageous, the efficacy of six weeks' treatment with 2 g 4-aminosalicylic acid (4-ASA) (n = 24) and 20 mg prednisolone enemas (n = 21) were compared in a double blind, randomised trial in patients with acute distal (less than 30 cm from the anus) ulcerative colitis. Baseline demography and clinical severity were similar in both groups. Five of 24 patients receiving 4-ASA and 4 of 21 receiving prednisolone did not complete the trial because of deteriorating symptoms, failure to improve, or side effects. At the time of leaving the trial, 24 hour stool frequency, the presence of blood in the stools, and histological and sigmoidoscopic appearances were similar in both groups. Symptomatic improvement occurred in 17 of 24 patients receiving 4-ASA compared with 11 of 21 receiving prednisolone (chi 2 = 1.62, NS). Complete symptomatic improvement occurred in 9 of 24 patients receiving 4-ASA compared with 5 of 21 receiving prednisolone (chi 2 = 0.98, NS). Histological improvement was seen in 9 of 24 patients on 4-ASA compared with 7 of 21 on prednisolone (chi 2 = 0.08, NS). One patient receiving 4-ASA was considered to have an idiosyncratic reaction to the drug but other side effects were not considered to be drug related. Thus, 4-ASA, previously used in the treatment of tuberculosis (para-aminosalicyclic acid), is as good as prednisolone in the treatment of distal ulcerative colitis and should be considered in patients unresponsive to steroids or in whom steroid treatment is undesirable.

Six patients with jejunostomies and residual jejunal lengths of 105 to 250 cm took the same food and water each day for eight study days. In random order, three methods of salt replacement were tested, each over 48 hours, against a period without added salt. During the three test periods the patients took 120 mmol of sodium chloride daily, as salt in gelatine capsules, as an isotonic glucose electrolyte (280 mOsmol/kg; 30 kcal) solution, and as a glucose polymer (Maxijul) solution (280 mOsmol/kg; 200 kcal). The daily stomal output remained constant for each patient during the four test periods but varied between patients from 0.60 to 2.84 kg (daily intestinal fluid balance 0.74-2.61 kg). Without a salt supplement, three patients lost more sodium from the stoma than they took in by mouth (-25, -94, and -101 mmol/day) and the mean sodium balance for all six subjects was -16 mmol (range -101 to 79) daily. Extra salt was absorbed with each form of supplement (p less than 0.05); no patient with the glucose electrolyte solution (mean 96, range 0 to 226 mmol), but one patient with the glucose-polymer solution (mean 96, range -25 to 164 mmol) and two with the salt capsules (mean 66, range -8 to 145 mmol) were in negative balance. Two patients vomited with the salt capsules. There was only a small increase in energy absorption (mean 115 kcal) with the glucose polymer solution compared with the glucose electrolyte solution. A sipped glucose electrolyte solution seems to be the optimal mode of sodium replacement in patients with a high output jejunostomy.

We have evaluated the predictive value of pelvic floor dysfunction (as characterized by abnormal contraction during defaecation straining or absent balloon expulsion) and evacuation proctography on symptomatic severe idiopathic constipation after colectomy with ileorectal or colorectal anastomoses for improvement and the use of laxatives. We also determined whether there was a relationship between the age of onset of symptoms and the symptomatic outcome after surgery. Forty-four women (mean age 34 years) were studied. Twenty patients had had a preoperative evacuation proctogram. Of these, 8 evacuated completely and 12 incompletely. Of the 29 patients in whom puborectalis electromyography was performed, 19 had paradoxal contraction on straining. There was no statistical relationship between symptomatic outcome and complete or incomplete evacuation on proctography, the presence or absence of puborectalis paradox or the age of onset of constipation (before or after the age of 10 years). Twenty-five patients had a preoperative balloon expulsion test. Of these, 14 were not able to expel a 50 ml water-filled balloon, and all 14 (100%) still experienced postoperative pain; 8 (57%) were still using laxatives. Of the 11 patients who were able to expel a balloon, 6 (55 %) experienced pain and 1 (11 %) still required laxatives postoperatively. The differences in postoperative pain and laxative requirements between those unable and those able to expel the balloon were statistically significant. Thus the balloon expulsion test may have predictive value when considering colectomy in patients with severe idiopathic constipation.

The outcome in 40 patients who underwent colectomy for idiopathic megacolon and megarectum over an 18 year period was evaluated. All patients had a radiologically dilated bowel and a bowel frequency of less than two per week. Twenty two patients had a caecorectal anastomosis, 11 had an ileorectal anastomosis (including one with a previous caecorectal anastomosis and four with a previous sigmoid resection), and seven had a sigmoid resection. The mean (range) age at operation was 35 (17-69) years. All three operations resulted in a normal bowel frequency in more than 80% of patients but no patient with an ileorectal anastomosis experienced recurrent constipation. Thirty four patients experienced pain preoperatively and this was still present in 14 patients postoperatively. One patient died and four required subsequent laparotomy for bowel obstruction. The functional outcome in patients with dilatation of the whole colon and in those with dilatation of the left colon did not differ. Subsequent surgery for constipation was performed in three patients. Colectomy offers good results with few complications in the treatment of idiopathic megacolon, and an ileorectal anastomosis is the preferred operation.

Since 1954, 34 patients have attended St. Mark's Hospital with pyoderma gangrenosum in association either with ulcerative colitis (22 patients) or Crohn's disease (12 patients). Lesions were multiple in 71 per cent and over half were situated below the knees. Ulcerative colitis was active in 11 patients (50 per cent) and Crohn's disease was active in nine (75 per cent) when pyoderma gangrenosum was diagnosed. Associated illnesses - most commonly a seronegative arthritis affecting large joints - were present in 55 per cent and 92 per cent of cases respectively. A diffuse pustular rash appeared in six patients, synchronously with pyoderma in five. In a further seven patients (two with ulcerative colitis, five with Crohn's disease) the onset or course of pyoderma might have been linked to the presence of non-dermatological suppuration. Pyoderma resolved without intestinal resection in two-thirds of patients. When present at the time of surgical resection (15 procedures in 13 patients), pyoderma healed promptly in six cases, only with additional therapy in four cases and very slowly or not at all in five cases. Pyoderma gangrenosum occurs in both ulcerative colitis and Crohn's disease. Healing after intestinal resection is unpredictable both with respect to timing and extent of resection.

SummaryInflammatory bowel disease (IBD) is characterized by a chronic relapsing intestinal inflammation, typically starting in early adulthood. IBD is subdivided into two subtypes, on the basis of clinical and histologic features: Crohn disease and ulcerative colitis (UC). Previous genomewide searches identified regions harboring susceptibility loci on chromosomes 1, 3, 4, 7, 12, and 16. To expand our understanding of the genetic risk profile, we performed a 9-cM genomewide search for susceptibility loci in 268 families containing 353 affected sibling pairs. Previous linkages on chromosomes 12 and 16 were replicated, and the chromosome 4 linkage was extended in this sample. New suggestive evidence for autosomal linkages was observed on chromosomes 1, 6, 10, and 22, with LOD scores of 2.08, 2.07, 2.30, and 1.52, respectively. A maximum LOD score of 1.76 was observed on the X chromosome, for UC, which is consistent with the clinical association of IBD with Ullrich-Turner syndrome. The linkage finding on chromosome 6p is of interest, given the possible contribution of human leukocyte antigen and tumor necrosis–factor genes in IBD. This genomewide linkage scan, done with a large family cohort, has confirmed three previous IBD linkages and has provided evidence for five additional regions that may harbor IBD predisposition genes.

Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) of unknown aetiology which are characterised by chronic inflammation of the gastrointestinal tract. Epidemiological studies suggest the presence of a genetic component in the aetiology of both CD and UC. A susceptibility gene for Crohn's disease has recently been mapped to the pericentromeric region of chromosome 16 (IBD1), and this finding has been replicated in two subsequent studies. Although CD and UC are distinct clinical entities, the fact that both disorders occur in a significant proportion of families with multiple cases of IBD suggests that overlapping sets of susceptibility genes may be involved. We have addressed this question for IBD1 by typing eight microsatellite markers from the locus in 70 kindreds affected with either UC only or with both UC and CD and analysing the data for linkage by both non-parametric and parametric methods. Evidence for linkage was detected in families affected with only UC, with a mean proportion of 0.70 affected sib pairs sharing alleles identical by descent at D16S3136 (p=0.01), and a peak non-parametric linkage score of 2.02 at D16S3120 with the GENEHUNTER program (p=0.02). The estimated sib relative risk attributable to IBD1 in these families was 1.46. Surprisingly, no evidence of linkage was detected in the families affected with both UC and CD (p>0.2). The data suggest that IBD1 may also contribute to susceptibility to ulcerative colitis, and that it is likely to be located in the 12 cM interval between D16S419 and D16S409.

Background & Aims: Inflammatory bowel disease (IBD) is a complex disorder of unknown etiology. Epidemiological investigations suggest a genetic basis for IBD. Recent genetic studies have identified several IBD linkages. The significance of these linkages will be determined by studies in large patient collections. The aim of this study was to replicate IBD linkages on chromosomes 12 and 16 in a large European cohort. Methods: Three hundred fifty-nine affected sibling pairs from 274 kindreds were genotyped using microsatellite markers spanning chromosomes 12 and 16. Affection status of the sibling pairs was defined as Crohn's disease (CD) or ulcerative colitis (UC). Results: Nonparametric statistical analyses showed linkage for both chromosomes. Two-point results for chromosome 12 peaked at D12S303 (logarithm of odds [LOD], 2.15; P = 0.003) for CD and at D12S75 (LOD, 0.92; P = 0.03) for UC. Multipoint analyses produced a peak LOD of 1.8 for CD. Chromosome 16 showed linkage for CD at marker D16S415 (LOD, 1.52; P = 0.007). Multi-point support peaked above markers D16S409 and D16S411 (LOD, 1.7). Conclusions: These data are consistent with linkage of IBD to chromosomes 12 and 16. The replication of genetic risk loci in a large independent family collection indicates important and common susceptibility genes in these regions and will facilitate identification of genes involved in IBD. GASTROENTEROLOGY 1998;115:1066-1071

BACKGROUND: It has been suggested that the incidence of inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is three or more times higher in northern than in southern Europe. The aim of this EC funded study was to investigate this apparent variation by ascertaining the incidence of IBD across Europe. METHODS: For the period 1 October 1991 to 30 September 1993 all new patients diagnosed with IBD were prospectively identified in 20 European centres according to a standard protocol for case ascertainment and definition. FINDINGS: Altogether 2201 patients aged 15 years or more were identified, of whom 1379 were diagnosed as UC (including proctitis), 706 as CD, and 116 as indeterminate. The overall incidence per 100,000 at ages 15-64 years (standardised for age and sex) of UC was 10.4 (95% confidence interval (95% CI) 7.6 to 13.1) and that of CD was 5.6 (95% CI 2.8 to 8.3). Rates of UC in northern centres were 40% higher than those in the south (rate ratio (RR) = 1.4 (95% CI 1.2 to 1.5)) and for CD they were 80% higher (RR = 1.8 (95% CI 1.5 to 2.1)). For UC the highest reported incidence was in Iceland (24.5, 95% CI 17.4 to 31.5) and for CD, Maastricht (The Netherlands; 9.2, 95% CI 6.5 to 11.8) and Amiens (north west France; 9.2, 95% CI 6.3 to 12.2). The lowest incidence of UC was in Almada (southern Portugal) (1.6, 95% CI 0.0 to 3.2) and of CD in Ioannina (north west Greece) (0.9, 95% CI 0.0 to 2.2). An unexpected finding was a difference in the age specific incidence of UC in men and women with the incidence in women but not men declining with age. INTERPRETATION: The higher overall incidence rates in northern centres did not seem to be explained by differences in tobacco consumption or education. Nevertheless, the magnitude of the observed excess for both conditions is less than expected on the basis of previous studies. This may reflect recent increases in the incidence of IBD in southern Europe whereas those in the north may have stabilised.

BACKGROUND: Short bowel patients with a jejunostomy have large volume stomal outputs, which may in part be due to rapid gastric emptying of liquid. Short bowel patients with a preserved colon do not have such a high stool output and gastric emptying of liquid is normal. AIMS: To determine if differences in the gastric emptying rate between short bowel patients with and without a colon can be related to gastrointestinal hormone changes after a meal. SUBJECTS: Seven short bowel patients with no remaining colon (jejunal length 30-160 cm) and six with jejunum in continuity with a colon (jejunal length 25-75 cm), and 12 normal subjects. METHODS: The subjects all consumed a 640 kcal meal; blood samples were taken for 180 minutes for measurement of gastrointestinal hormones. RESULTS: Patients with a colon had high fasting peptide YY values (median 71 pmol/l with a colon; 11 pmol/l normal subjects, p < 0.005) with a normal postprandial rise, but those without a colon had a low fasting (median 7 pmol/l, p = 0.076) and a reduced postprandial peptide YY response (p < 0.050). Motilin values were high in some patients without a colon. In both patient groups fasting and postprandial gastrin and cholecystokinin values were high while neurotensin values were low. There were no differences between patient groups and normal subjects in enteroglucagon, pancreatic polypeptide, or somatostatin values. CONCLUSIONS: Low peptide YY values in short bowel patients without a colon may cause rapid gastric emptying of liquid. High values of peptide YY in short bowel patients with a retained colon may slow gastric emptying of liquid and contribute to the "colonic brake'.

BACKGROUND: Some metallic compounds, especially of zirconium, can cause cell mediated granulomatous inflammation of the skin. Pigment granules containing compounds of aluminium, silicon, and titanium have been observed within macrophages in the wall of the small intestine in health and in Crohn9s disease. Zirconium compounds can be ingested in toothpaste. AIM: To determine in a pilot study if granulomatous sensitivity can be detected to compounds of these metals or silicon after injection into the skin of patients with Crohn9s disease. SUBJECTS: Eight patients with Crohn9s disease known to have had granulomata in the intestine and not currently treated with corticosteroids, and two healthy controls. METHOD: Two intradermal injections each of 0.1 ml of a 0.02% suspension of one of the compounds made in the abdominal wall of each subject. The site was marked and full thickness skin biopsy performed six weeks later. RESULT: A foreign body granuloma was observed on histological examination of two biopsy specimens but no evidence of a cell mediated response in any subject. CONCLUSION: No support was found for the hypothesis that Crohn9s disease is due to a specific sensitivity to ingested metallic or silicon compounds.

International audience; Crohn's disease (CD) and ulcerative colitis are the major forms of chronic inflammatory bowel diseases in the western world, and occur in young adults with an estimated prevalence of more than one per thousand inhabitants. The causes of inflammatory bowel diseases remain unknown, but genetic epidemiology studies suggest that inherited factors may contribute in part to variation in individual susceptibility to Crohn's disease. A genome-wide search performed on two consecutive and independent panels of families with multiple affected members, using a non-parametric two-point sibling-pair linkage method, identified a putative CD-susceptibility locus on chromosome 16 (P less than 0.01 for each panel). The localization was centered around loci D16S409 and D16S419 by using multipoint sibpair analysis (P less than 1.5x10(-5)). This region of the genome contains candidate genes which may be relevant to the pathogenic mechanism of inflammatory bowel diseases.

Pouchitis may complicate the construction of an ileal pouch after colectomy for ulcerative colitis (UC) but not familial adenomatous polyposis (FAP). To examine whether differences in eicosanoid metabolism might explain why pouchitis is largely confined to UC patients, this study compared arachidonic acid stimulated release of immunoreactive leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) from macroscopically uninflamed pouch mucosal biopsy specimens incubated in vitro from patients with UC and FAP. The study also compared eicosanoid release from inflamed and uninflamed pouches in patients with UC. In uninflamed pouches, median LTB4 release was nearly twice as high in UC as in FAP (p = 0.001), but there was no significant difference in PGE2 production. In UC, stimulated eicosanoid release from uninflamed functioning pouch mucosa was not significantly different from that from either ileostomy or defunctioned pouch mucosa. LTB4 and PGE2 release were significantly greater from inflamed than uninflamed pouch mucosa in UC (p = 0.001 and 0.01, respectively). Leukotriene synthesis inhibition or receptor antagonism, or both merit therapeutic evaluation in pouchitis. Increased release of LTB4 from endoscopically normal pouch mucosa suggests increased 5-lipoxygenase activity in patients with UC and could contribute to their predisposition to pouchitis.

An increased incidence of carcinoma of the small bowel and colon has been described in patients with Crohn's disease. Tumours arising in the rectum and anus are reported less often. Between 1940 and 1992, of some 2500 patients with Crohn's disease seen at this hospital, 15 are known to have developed carcinoma of the lower gastrointestinal tract. Malignancy occurred in the colon in two patients, in the upper two thirds of rectum in one, in the lower third of rectum in seven, and in the anus in five. The 12 patients with carcinoma arising in the anus or lower rectum had longstanding severe anorectal Crohn's disease, which included a stricture in four, fistula in four, proctitis in one, abscess in two, and enlarged anal skin tags in one. The development of malignancy in patients with Crohn's disease may apply particularly to those with chronic complicated anorectal disease.

Many patients with severe idiopathic constipation complain of upper gastrointestinal symptoms, and these often persist after subtotal colectomy. To determine if there is a disturbance of upper gastrointestinal motility in this condition, we have studied gastric emptying for solids (111In-containing pancake) and liquids (99mTc-containing orange juice) for a longer period after a meal (6 hr) than in previously reported gastric emptying studies. Small bowel transit for solids was also measured. All patients had emptied their colon the day before the study. Twelve women (mean age 36 years) with a bowel frequency of less than once per week, proven slow intestinal transit, and a normal diameter colon were studied. Twelve healthy controls (eight female and four male, mean age 33) were also studied. As a group the constipated patients demonstrated no statistically significant delay in emptying during the first 3 hr, although the emptying rate for three of 12 individuals fell outside the normal range. However, at 6 hr after ingestion of the meal, six of 10 patients had residual gastric contents greater than normal--up to 48% solid residue (median: 11% for patients and 0% for controls, P < 0.01) and 40% of liquid (median 9% vs 0%, P < 0.01). Three of four patients with upper gastrointestinal symptoms 6 hr after the meal had gastric retention of solids markedly outside the normal range (48%, 32%, and 16%; normal < 4%). Small bowel transit time was assessed as the time for the solid phase to pass from the duodenum to the cecum; the constipated patients demonstrated delayed transit (median: 75 vs 55 min, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Radio-opaque markers have a well established role in distinguishing between patients with normal and those with slow intestinal transit, but in the latter group their accuracy in defining the region of delay has not been established. To study regional colonic transit accurately the transit of a radioisotope labelled meal was determined and findings were compared with those of simultaneously ingested radio-opaque markers. Twelve healthy controls (mean age 33 years) and 12 severely constipated women (mean age 36 years, bowel frequency < once per week) were studied On day 1, a meal containing 10 MBq 111In bound to 0.7 mm resin microspheres was ingested. Subjects also ingested a set of radiologically distinguishable markers on three successive days. Abdominal scans were obtained three times daily for 7 days. Abdominal radiographs were obtained after 72 or 96 hours and again at 144 or 168 hours. Eight 'regions of interest' were created--one for the small bowel, six for the colon, and one for excreted stool. The constipated patients all showed colonic transit outside the normal range, with a variable site of delay demonstrated by time activity curves for each region. To provide a different measure of the effectiveness of colonic transport, the movement of the 'centre of mass' for the radioisotope and for the markers was then determined. The radioisotope and radiopaque marker methods gave similar results. At all times between 24 and 144 hours there was no significant difference for the position of the centre of mass between the radio-opaque and marker methods. At all times, however, the mean difference between the markers and the radioisotopes was positive, indicating that the center of mass of the markers was always head of that of the radioisotope. The mean difference between the methods was never greater than one region of interest, and ranged from 12 to 72% of one region of interest in the colon. The difference between these two methods could reach up to two colonic segments in certain patients at one time. Radioisotope ingestion provides accurate information about the transit through individual colonic regions because of the possibility of frequent observations and the clear delineation of the entire colon. Although these features were not obtained with radio-opaque markers, they are suitable as a screening test for the presence and pattern of colonic delay.

A combined manometric and radioisotope study is described which was designed to investigate the motility characteristics of induced defaecation in the colon, rectum and anal canal, in patients with severe constipation. Five women with severe idiopathic constipation, aged 30–45 years, were studied. A multiple channel water-perfused manometric tube was placed colonoscopically into either the whole colon or left colon to monitor pressure activity. In two whole-colon studies, 5.5 MBq 111In DTPA and later 9 MBq 99mTc DTPA were instilled into the colon to monitor the transit of colonic contents in response to two separate stimuli. Motor activity was initiated on both occasions by intraluminal instillation of 5.5 mg bisacodyl. In the whole-colonic studies a right colonic stimulus initiated multiple high-pressure peristaltic waves which traversed the entire length of the colon. The bowel was then refractory to a second stimulus at the splenic flexure. In the five left colonic studies, a stimulus at the splenic flexure produced high-pressure peristaltic waves which proceeded distally, and which included a rise in rectal pressure. The anal canal relaxed simultaneously with the onset of peristalsis high in the left colon, and remained relaxed until the pressure wave reached the anus and bowel content had been expelled. In both types of study high-pressure waves corresponded to the effective transport of radioisotope. The constipated patients showed a coordinated motor response to the stimulus. The passage of flatus coincided with a simultaneous pressure rise in the distal colon and rectum, together with anal relaxation. These findings confirm previous observations that the defaecation induced by a luminal stimulant consists of colonic peristalsis, rectal contraction, and early anal relaxation. The ability to generate this sequence of motor activity is preserved in patients with severe idiopathic constipation.

Bowel resection for idiopathic megarectum and megacolon does not always predictably relieve symptoms and has a significant morbidity. We have therefore evaluated the results of stoma formation in this condition. All patients had a bowel frequency of less than one per week, and all had a dilated rectum or colon. Eight patients, six of whom had had a previous unsuccessful operation for their constipation, had a colostomy — this relieved the constipation and the need for laxatives in all six patients with rectosigmoid dilatation, although one patient could not tolerate his stoma. Two patients with dilatation of the whole colon were not helped. An ileostomy was formed in four patients with previous colonic resection, with relief of constipation in all. However pain and abdominal distension were common persistent symptoms in both groups. Four patients with a colostomy and all four patients with an ileostomy felt subjectively improved with a stoma. Stoma formation is a viable alternative to more major surgery, either as a primary procedure or after previous surgery has failed.

Increased mucosal eicosanoid synthesis occurs in active ulcerative colitis; suppression of the synthesis of pro-inflammatory leucotrienes could be therapeutically useful. Neutrophil 5-lipoxygenase is calcium-dependent. In this study, the effect of the calcium channel antagonist, verapamil, on the release of eicosanoids by colitic rectal mucosal biopsies has been examined. Verapamil in therapeutic concentration (5 micrograms/ml, 10(-5) M) reduced leucotriene B4 release from actively inflamed rectal mucosa by 30% (from 60 (5.0 S.E.M.) ng/g wet weight/20 min without, to 42 (5.7 S.E.M.) with verapamil, P less than 0.05), but had no effect on leucotriene B4 release by rectal biopsies taken from patients with quiescent ulcerative colitis (39 (2.8 S.E.M.) ng/g wet weight/20 min without, and 43 (5.0 S.E.M.) with verapamil). Verapamil did not affect mucosal prostaglandin E2 release. The results suggest that, in active ulcerative colitis, verapamil inhibits mucosal 5-lipoxygenase activity and warrants therapeutic evaluation.

The time taken for radio-opaque markers to pass through the intestine has been measured in 25 healthy men, and 18 healthy women in both the follicular and luteal phases of the menstrual cycle. The subjects collected all stools after ingestion of the markers, the number of markers present in each stool was counted on a radiograph, and the number of markers retained in the body was thus determined for 12 hourly intervals after ingestion. The mean values (2 standard deviations) for men and women in both phases of the menstrual cycle proved to be so similar that the results have been combined to provide a single normal range. These data for the normal range for retained markers (as assessed by plain radiograph) are presented in diagrammatic form for clinical use. To assess whether a patient's whole gut transit time lies within the normal range a single type of marker can be used and an abdominal radiograph performed at 12 or 120 hours, the limits of the normal range. Normal subjects retain more than 20% of markers within 12 hours and less than 80% after 120 hours. If desired more information can be gained by giving different types of marker on successive days, so that several transit studies providing intermediate values can be obtained from a single abdominal radiograph at 120 hours.

Specimens of the sigmoid colon were obtained from male and female patients (n = 11) with carcinoma of the colon or rectum and studied immunohistochemically for vasoactive intestinal polypeptide-, somatostatin-, substance P-, neuropeptide Y-, calcitonin gene-related peptide-, met- and leu-enkephalin-, 5-hydroxytryptamine-, and dopamine beta-hydroxylase-containing nerves. In the subdivisions of the submucous plexus (namely, Schabadasch's, Meissner's, and the intermediate plexuses), substance P- and vasoactive intestinal polypeptide-immunoreactive nerve fibers were the most numerous, and equal densities of these nerves were found in all three layers. In contrast, few neuropeptide Y-, met-enkephalin-, leu-enkephalin-, calcitonin gene-related peptide-, somatostatin-, 5-hydroxytryptamine-, and dopamine beta-hydroxylase-immunoreactive nerves were found in these regions. The nerve cell bodies of the submucous plexus contained vasoactive intestinal polypeptide, substance P, leu-enkephalin, somatostatin, and 5-hydroxytryptamine but not neuropeptide Y, met-enkephalin, calcitonin gene-related peptide, and dopamine beta-hydroxylase. Vasoactive intestinal polypeptide-containing nerve cell bodies were found in all three subdivisions. Substance P-, leu-enkephalin-, and somatostatin-immunoreactive nerve cell bodies were found in Schabadasch's plexus and the intermediate region of the submucous plexus, but they were absent from Meissner's plexus; 5-hydroxytryptamine-containing nerve cell bodies were only observed in Schabadasch's plexus. The possible function of the neuropeptide-, dopamine beta-hydroxylase-, and 5-hydroxytryptamine-containing neurons in the different layers of the submucous plexus is discussed.

Ten patients with an end jejunostomy and one with a jejuno-rectal anastomosis (jejunal length 30-140 cm) ate a constant chosen diet for 2 control days, and 2 test days when 40 mg omeprazole orally was taken each morning. In the 7 patients with a net secretory output of fluid, there was a mean reduction in wet weight of 0.66 kg/24 h (range -0.16 to 1.45 kg/24 h; P less than 0.05) and sodium 46 mmol/24 h (-51 to 135 mmol/24 h; N.S.); the four patients with net absorption of fluid showed no reduction in intestinal output. One patient with 30 cm jejunum responded little to oral but did so to intravenous 40 mg omeprazole twice a day with a reduction in wet weight of 3.00 kg/24 h and sodium 157 mmol/24 h. In one patient oral 40 mg omeprazole daily gave equivalent results to oral 300 mg ranitidine twice daily; in 2 others it was equivalent to intravenous 50 micrograms octreotide twice daily. Omeprazole reduces the intestinal output in patients with the short bowel syndrome and a net secretory output, but not enough to prevent the need for parenteral fluid and electrolyte replacement.

The results of the Duhamel operation in patients with idiopathic megarectum and megacolon have been reviewed. Twenty patients (14 males, six females) underwent the Duhamel operation over a 17-year period for this condition. The mean age at operation was 25 years; the mean age of onset of constipation was 3 years; and the mean follow-up period was 4·5 years. All the resected colons were of enlarged diameter. There was agreement between the preoperative radiographs and the operative specimens with regard to which parts of the rectum and colon were dilated. Subjective feelings of well-being were generally improved by surgery, as was bowel frequency in ten patients. Soiling, straining, abdominal pain and distension were, however, common after operation. Early complications were also common and five patients required further surgery for constipation. The Duhamel operation for megarectum and megacolon is characterized by an improved sense of well-being and improved bowel frequency, but it is associated with the persistence of many symptoms and further surgery is often required.