Liver disease in ulcerative colitis: an epidemiological and follow up study in the county of Stockholm.

In an epidemiological study of the incidence of ulcerative colitis (UC) in the county of Stockholm between 1955 and 1979, 1274 patients with UC were discovered. Almost all these patients had regularly been investigated with liver function tests; 142 (11%) of them showed signs of hepatobiliary disease. A follow up study on all 142 patients with abnormal liver function and UC was made between 1989 and 1991 to evaluate the cause of the liver abnormality and to find out if the liver disease had affected the survival rates. At follow up, eight patients were reclassified as having Crohn's disease, 60 had developed normal liver function as judged from test results, while the remaining 74 still had signs of hepatobiliary disease. The most common explanation for a transient abnormality in liver function was active colitis. The temporary signs of liver injury were not associated with changes in survival rates for these patients. Infections, especially those because of hepatitis B and C virus transmitted by blood transfusions accounted for the abnormalities in liver function in 21 patients, nine of which had a chronic, but non-fatal course. Twenty nine (2.3%) of the patients developed primary sclerosing cholangitis (PSC), and 12 of them died during the study period four because of cholangiocarcinoma and eight because of hepatic failure; one patient had a transplant. The estimated median time of survival from the first presentation of evidence of a liver function, compatible with the diagnosis of PSC, to death or liver transplantation was 21 years. A comparison of survival rates in patients with UC and patients with UC and concurrent PSC showed, a significant reduction in survival in the PSC group (p<0.0001). The number of patients with UC who developed PSC remained constant during the study period. Thus, although evidence of abnormal liver function is a common finding in UC, a spontaneous return to normal levels is common. In this study, which did not have a selection bias, the median time of survival among PSC patients was far longer than previously described although development of PSC among patients with UC does significantly reduce the estimated median time of survival.

The effect of omeprazole and ranitidine on ulcer healing, relief of symptoms, and incidence of adverse events in the treatment of duodenal ulcer patients.

In a Swedish double-blind multicenter study involving 143 patients, the new proton pump inhibitor omeprazole (30 mg taken as a single morning dose) was compared with ranitidine (400 mg b.i.d.). Clinical assessment and laboratory investigations were carried out at 2 and 4 weeks, and again at 6 weeks if patients had not healed earlier. Endoscopy was repeated at two-weekly intervals until the ulcer was healed. The patients in the two treatment groups were well matched prior to treatment. There was a higher ulcer healing rate in the omeprazole group (70%) than in the ranitidine group (55%) after two weeks of treatment. This difference reached statistical significance in 128 patients adhering to the protocol as shown by a logit model analysis with drug, ulcer size and smoking as the prognostic factors (p = 0.04). There were no major differences between the two treatment groups in terms of symptomatic relief. Both drugs were generally well tolerated, and the number of adverse events in the two treatment groups were similar. After healing, 127 patients entered a follow-up study, with endoscopy either after 6 months or on recurrence of symptoms. There was no significant difference between the two treatment groups, with the relapse frequency within 6 months being 39% in the omeprazole group and 47% in the ranitidine group. These results, with a 15 percentage points higher ulcer healing rate for omeprazole as compared with H2-receptor antagonists after two weeks, are in accordance with results reported in other studies.

Extracolonic diagnoses in ulcerative colitis: an epidemiological study.

In a population-based study of 1274 patients with ulcerative colitis (UC), the overall prevalence of extracolonic diagnoses was 21%. Seventy percent of patients with extracolonic diagnoses had extensive colitis. Patients without extracolonic diagnoses had only 28% extensive colitis (p less than 0.001), compared with 37% in the entire test population. The prevalence was higher in familial UC (p less than 0.05). The extracolonic diagnoses could be classified into two major groups, activity related and autoimmune, with regard to the extent and activity of UC and to the effects of medical and surgical treatment. Three hundred sixty-four diagnoses were distributed in 271 UC patients. It is concluded that extracolonic diagnoses are less frequent in an unselected patient group. However, extracolonic diagnoses are associated with the extent of UC at the time of diagnosis and with familial UC, and they can be classified as either activity related or autoimmune, with characteristic combinations of several extracolonic diagnoses occurring in 25% of the 271 patients.

Prognosis and mortality of ulcerative colitis in Stockholm County, 1955-1979.

All 1274 patients in Stockholm County who were diagnosed as having ulcerative colitis during the 25-year period 1955-79 were followed up and studied with regard to prognosis and mortality. There were 109 deaths recorded--41 caused by ulcerative colitis and 68 from other causes. The cumulative survival probability (computed by life-table methods) was worse than expected. For males it was approximately 80% at 20 years, to be compared with the approximately 97% expected in the background population. For females the corresponding figures were approximately 85% and 98%, respectively. The excess death risk increased with increasing age and was more commonly due to unrelated causes than to ulcerative colitis as such. In patients with total colitis at onset the death risk was greater than for other patients during the first years of disease. Thereafter the prognosis was, if anything, better than in other cases. There was no major change in postoperative mortality or general mortality pattern during the 25 years of observation.

Prevalence of inflammatory bowel disease among relatives of patients with ulcerative colitis.

The familial occurrence of inflammatory bowel disease (IBD) was investigated among 963 patients with ulcerative colitis (UC) diagnosed in 1955-1979 in Stockholm County. For 76 patients who had a relative with IBD a pedigree was drawn. The diagnoses of the diseased relatives were verified. There was a general prevalence of 7.9% for IBD among relatives. In 80% one relative was affected, in most cases a first-degree relative with UC. Sibship was the commonest relationship. No concordance for UC was found among three pairs of monozygotic twins. The prevalence of UC in first-degree relatives was 15 times higher than in non-relatives. The age of onset was significantly lower among patients with a family history for UC; they also had a higher incidence of total colitis. The prevalence of Crohn's disease in first-degree relatives of patients with UC was almost 3.5 times higher than in non-relatives.

Incidence of ulcerative colitis in Stockholm County 1955-1979.

The epidemiology of ulcerative colitis in Stockholm County over a 25-year period, 1955-79, was investigated. Only definite cases in accordance with specified acceptance criteria were included. There were 1274 cases--681 males and 593 females. The proportion of patients with proctitis, left-sided, and total extent of disease of diagnosis remained constant over the study period, as did the time interval between onset of symptoms and definite diagnosis. The peak incidence in relation to age increased slightly but remained in the 3rd and 4th decade through the study period. The incidence in men over 40 years old increased markedly towards the end of the study.

Rectal bioavailability of bacampicillin hydrochloride in man as determined by reversed-phase liquid chromatography.

The relative bioavailability of bacampicillin hydrochloride, a pro-drug of ampicillin, was compared after rectal and oral administration. Bacampicillin was administered rectally as a microenema . The oral formulation was an aqueous microcapsule suspension. They were given as single doses of 400 mg to 12 healthy volunteers after overnight fasting using a randomized cross-over design. Ampicillin and bacampicillin were determined in plasma and blood, respectively, using HPLC. Bacampicillin was rapidly absorbed from the rectum but to a much smaller degree compared to the oral dose. The median t-max was 0.5 and 0.75 h after the rectal and oral doses, respectively. The mean (SD) Cp-max was 1.2 (0.33) mg/l after rectal and 4.8 (0.98) mg/l after oral administration, respectively. Blood concentrations of bacampicillin were extremely low or undetectable with no indication of differences between the two modes of administration. The 95% confidence limits for the relative bioavailability of the microenema were 22.4-39.2 and 22.5-40.4% based on area under the plasma concentration time curve and urinary recovery, respectively. The rectal dose was followed by distress, diarrhea or pain, in 7 subjects. There were no adverse reactions after the oral dose. Bacampicillin was unaffected by beta-lactamases produced by intestinal bacteria.