Sten Nørby Rasmussen

Assessment of the Diagnoses of Crohn's Disease and Ulcerative Colitis in a Danish Hospital Information System

BACKGROUNDnOur aim was to estimate the completeness-that is, whether all patients were included in the system-and the validity-that is, whether the diagnostic criteria were fulfilled for the patients registered-of the diagnoses of Crohns disease and ulcerative colitis in a Danish hospital system.nnnMETHODSnInformation in a regional hospital system, in the County of North Jutland, Denmark, was compared with hospital records and information in a pathology system.nnnRESULTSnThe analysis of the completeness included 143 patients with Crohns disease and 285 patients with ulcerative colitis. The completeness of the regional hospital system using the pathology system as a reference standard was 94% for both diseases. The analysis of the validity included 281 patients registered as having Crohns disease and 506 patients registered as having ulcerative colitis. The validity of the two diagnoses was 97% and 90%, respectively.nnnCONCLUSIONSnThe regional hospital system showed few misclassifications of the diagnoses of Crohns disease and ulcerative colitis. Thus the nationwide hospital system (based on the regional hospital systems) may provide a unique study base for future research.

Hepatobiliary Dysfunction and Primary Sclerosing Cholangitis in Patients with Crohn's Disease

BACKGROUNDnOnly a few studies have attempted to determined the prevalence of long-standing abnormal liver function and primary sclerosing cholangitis (PSC) in patients with Crohns disease (CD). The aim of the study was to determine the prevalence of long-standing abnormal liver function test results and to describe the clinical, biochemical, and histologic findings in patients with large-duct classic PSC and small-duct PSC (that is, normal cholangiogram) in patients with CD during a 15-year period.nnnMETHODSnPatients with CD and long-standing abnormal liver function results were investigated individually with endoscopic retrograde cholangiography and liver biopsy.nnnRESULTSnOf 262 consecutive patients with CD, 38 (15%) had long-standing increased alkaline phosphatase (ALP) values (mean, 1065 U/l; range, 321-4165 U/l). Of these, 10 patients were classified as having hepatic disease (4%), of which 9 had PSC and 1 had a non-specific reactive hepatitis. Of nine patients with PSC (3.4%), three were classified as having large-duct PSC; five, small-duct PSC; and one, unclassified. In patients with large-bowel CD (n = 102) the prevalence of PSC was 9%. Mean age at diagnosis of PSC was 35 years (22-46 years), and the female to male ratio, 7:2. All PSC patients had large-bowel involvement (P < 0.00015), and two of them developed colonic carcinoma of the large bowel (P < 0.01). All cases of small-duct PSC were stage 1, whereas large-duct PSC were stage 2-3. During the observation period (mean, 5.4 years) no PSC patients died.nnnCONCLUSIONSnThe results of our study indicate that PSC is the major hepatic disease in patients with CD and long-standing abnormal liver function tests and is approximately as prevalent as in ulcerative colitis. Patients with PSC and CD may have a milder liver disease than patients with PSC and ulcerative colitis, perhaps because large-duct PSC is less common in patients with CD. Cholangiograms and liver biopsies are both needed to evaluate the extent of the disease.

Very low intraluminal colonic pH in patients with active ulcerative colitis

Intraluminal gastrointestinal pH was measured in seven patients with active ulcerative colitis (four male, three female). A radiotelemetry capsule was used, and its location was determined by fluoroscopy. Satisfactory measurements were obtained from six, in all of whom pH levels were normal in the stomach and small intestine. Three patients also had normal pH values in the colon. However, in the remaining three patients very low pH levels (lowest values 2.3, 2.9, and 3.4) were found in the proximal parts of the colon. Five of the seven patients, including the three with low pH in the colon, underwent colectomy. The mechanism behind the low intraluminal pH in some patients with ulcerative colitis is speculative. Increased fecal concentrations of lactate occur in active disease, but some of the pH values measured in our study were below the pKa value of lactate. The study demonstrates that very low intraluminal pH levels in the colon occur in some patients with active ulcerative colitis. This might be an indicator of severe activity of the disease.

5-Aminosalicylic Acid in the Treatment of Crohn's Disease: A 16-Week Double-Blind, Placebo-Controlled, Multicentre Study with Pentasa®

The response to 5-aminosalicylic acid (5-ASA) in mild and moderately active Crohns disease localized in the small bowel was studied in a randomized, double-blind, placebo-controlled trial in four centres. Sixty-seven patients were included, of whom 30 were treated with 1500 mg slow-release 5-ASA/day (Pentasa) for a scheduled period of 16 weeks. In the 5-ASA group 40% of the patients improved, versus 30% of the placebo-treated group (intent to treat basis; p greater than 0.1). Four of the patients treated with 5-ASA left the study owing to disease deterioration, versus 10 of the placebo-treated patients (p greater than 0.2). Seventeen patients were secondarily excluded, and the remaining 50 patients (23 receiving 5-ASA) were reevaluated in greater detail. No statistically significant differences in outcome were shown. Three patients (one given 5-ASA) were withdrawn from the study because of presumed side effects, but no serious adverse reactions were recorded. The present results indicate that 5-ASA, at least in the dosage used, is not superior to placebo. Nevertheless, trends towards a beneficial effect in Crohns disease in the small bowel justify further clinical trials with a larger dosage of 5-ASA.

Treatment of Crohn's Disease With Peroral 5-Aminosalicylic Acid

Eighteen patients with active Crohns disease entered an open trial with 5-aminosalicylic acid in a slow-release preparation. All had lesions of the small bowel. Ten of them also had Crohns disease of the colon. 5-Aminosalicylic acid, 500 mg three times daily, was administered for 6 wk. Even with meticulous monitoring, no side effects of any kind were observed, particularly no cases of renal affection, which could have been expected from animal studies. The clinical course was estimated as improved in 13 patients (72%), unchanged in 2 patients (11%), and aggravated in 3 patients (17%); 2 of these 3 were withdrawn from the study and switched to alternative treatment. The Crohns disease activity index decreased from a median of 226 points to 99 points. On the basis of these results, large-scale controlled therapeutic trails seem warranted in order to establish clinical evidence for the benefit of peroral treatment with 5-aminosalicylic acid in patients with Crohns disease.

Comparative bioavailability of 5-aminosalicylic acid from a controlled release preparation and an azo-bond preparation

Background: Knowledge of the bioavailability of 5‐aminosalicylic acid (5‐ASA, mesalazine) from the different 5‐ASA‐containing drugs is important for rational therapy of inflammatory bowel diseases.

Post-operative infections of osteoplastic compared with free bone flaps

A retrospective study was performed to evaluate the rate of infection in free and osteoplastic bone flaps after craniotomy. Two hundred and two craniotomies were performed in 98 cases of tumour, 35 cases of trauma and 69 cases of vascular disease. The overall incidence of infection was 6.4% (13 cases). The infectious agents were Staphylococcus aureus in four cases; Pneumococcus and gram-positive rods each in one case. In seven cases no infectious agent was identified. In 127 cases with free bone flaps eight (6.3%) were infected, and in 75 cases with osteoplastic bone flaps five (6.7%) were infected. One of five (20%) osteoplastic and four of eight (50%) free bone flaps had to be removed in order to accomplish healing, suggesting that an osteoplastic bone flap may be preserved more often in cases of infection.

Bioavailability of 5-aminosalicylic acid from slow release 5-aminosalicylic acid drug and sulfasalazine in normal children

The bioavailability of a controlled release 5-aminosalicylic acid preparation (Pentasa) was investigated in nine healthy children after a medication period of six days (1000 mg/day) and compared with sulfasalazine (Salazopyrin) (2000 mg/day). The local bioavailability in the distal gut lumen, reflected by the 5-aminosalicylic acid concentration in the fecal water, showed comparable values after Pentasa (4.44 mmol/liter) and Salazopyrin (6.25 mmol/liter). The concentration ofN-acetyl-5-ASA was significantly higher after Pentasa, reflecting the more proximal release of 5-aminosalicylic acid compared with Salazopyrin. No relation was found between the 5-aminosalicylic acid fecal water concentration and the 5-aminosalicylic acid dose per kilogram of body weight. The urinary excretion of 5-aminosalicylic acid andN-acetyl-5-aminosalicylic acid was higher after Pentasa than after Salazopyrin (32% vs 25%). Dose interval plasma concentration curves showed low values after both preparations. Based on the concept that the fecal water concentration is decisive for the efficacy of 5-aminosalicylic acid in distal inflammatory bowel disease, Pentasa treatment offers a relevant alternative in cases of Salazopyrin intolerance or allergy in children. The higher systemic bioavailability from Pentasa warrants monitoring of the renal function.

Effect of Olsalazine and Mesalazine on Intraluminal pH of the Duodenum and Proximal Jejunum in Healthy Humans

BACKGROUNDnTreatment of inflammatory bowel disease with olsalazine causes diarrhoea in 10% of patients. This is claimed to be caused by a drug effect on mucosal transport in the small intestine, which might be reflected in the intraluminal pH. We aimed to study the effect on jejunal pH of olsalazine (Dipentum) and an alternative preparation, slow-release mesalazine (Pentasa).nnnMETHODSnThirteen healthy volunteers, seven male and six female, participated in a randomized, crossover study. Steady-state conditions were obtained after ingestion of 2 g or 6 g mesalazine daily or 2 g olsalazine daily for 1 week. The pH of the duodenum and proximal jejunum was measured by using pH-sensitive, radiotransmitting capsules, the location of which was confirmed by fluoroscopy.nnnRESULTSnNo effect of either drug on duodenal pH was detected. Mean duodenal pH ranged from 6.18 to 6.22. The mean pH of the pre-medication proximal jejunum was 6.02. Mesalazine had no significant effect, but olsalazine significantly increased the pH of the proximal jejunum (mean pH, 6.47).nnnCONCLUSIONSnOur results indicate that the effect of olsalazine on jejunal transport of electrolytes and water, observed in experimental studies, also applies to human subjects in steady-state conditions, and adaptation does not occur within 6 days.

Campylobacter pylori in esophagus

5. Roediger WEW: The colonic epithelium in ulcerative colitis: An energy-deficiency disease. Lancet 2:712-715, 1980 6. Dirksen G: Acidosis. In Physiology of Digestion and Metabolism in the Ruminant. AT Phillipson (ed). Newcastleupon-Tyne, England, Oriel Press, 1970, pp 612-625 7. Essig HW, Huntington GB, Emerick RJ, Carlson JR: Nutritional problems related to the gastro-intestinal tract. In The Ruminant Animal--Digestive Physiology and Nutrition. DC Church (ed). Englewood Cliffs, New Jersey, Prentice Hall, 1988, pp 474-480