Pouchitis--predictable by immunological or genetic markers?
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Biomarkers↗
Biomedical subjects
V Binder
Publications and source records attributed to V Binder.
Changes in extent of ulcerative colitis: a study on the course and prognostic factors.
BACKGROUND: The prognosis of patients with ulcerative colitis (UC) has previously been described with regard to mortality, cancer occurrence, and need for colectomy on the basis of an annual follow-up of a regional cohort of UC patients in Copenhagen County diagnosed in 1962-87. The objective of this study was to examine the prognosis with regard to spread of disease and to evaluate possible prognostic factors with regard to spread of disease and colectomy by multivariate regression analysis. METHODS: An inception cohort of 1161 patients with UC was examined by actuarial analysis and by multivariate regression analysis of a subgroup of 467 patients diagnosed in 1979-87. RESULTS: The probability for further progression of proctosigmoiditis, evaluated by sigmoidoscopy and radiology, was 53% after 25 years. The probability for regression was 76.8% for substantial colitis and 75.7% for pancolitis after 25 years. Multivariate regression analysis showed that the occurrence of the symptoms abdominal pain and diarrhoea was prognostically unfavourable with regard to the progression from proctosigmoiditis. Age influenced the regression probability in extensive disease. With regard to colectomy the following variables influenced the prognosis: fever, general condition, serum albumin, mucopus in stools, and diarrhoea at onset. CONCLUSIONS: Disease extent in UC is not static but changes with time in approximately half of the patients. This finding should have implications for the follow-up. Ulcerative proctitis should be considered the same disease as UC and needs the same long-term follow-up.
Actuarial Analysis↗
Epidemiology in gastroenterology.
A review of the literature on gastrointestinal epidemiology during the last 25 years shows a comprehensive contribution from Danish studies. This is partly explained by very favourable conditions in Denmark for epidemiological research, due to various valid registers and a long tradition for longitudinal population and patient cohorts. Data are presented on prevalence, incidence, demography, clinical risk factors, clinical course, and prognosis of various gastrointestinal disorders. Main emphasis is put on Danish studies, which are compared with international results. Present possibilities for prophylaxis against gastrointestinal diseases and delimitation of treatment of benign diseases are discussed. It is expected that research within gastrointestinal epidemiology in Denmark will increase in the coming years.
Denmark↗
Disease activity courses in a regional cohort of Crohn's disease patients.
BACKGROUND: The study was a follow-up of an inception cohort of 373 patients with Crohn's disease. METHODS: Annual assessments, life table analyses, and Markov chain analyses, estimating the probability for remission and relapse with time, and working capacity were carried out. RESULTS: The clinical course of Crohn's disease differs markedly over time, from ever-relapsing cases to a quiescent course with remission for several years, interrupted by years with relapse. No predictive factors have been found for the subsequent course with regard to age, sex, extent of disease at diagnosis, and treatment in the year of diagnosis. The relapse rate within the year of diagnosis and the following 2 years, however, does correlate positively (p = 0.00001) with the relapse rate in the following 5 years. Furthermore, the relapse rate for 1 year during the disease course influences the relapse rate the following year, indicating a disease pattern over time with waves of at least 2 years' duration. A slight tendency towards burning out was found. The disease course reflected in working capacity for the patients showed that a minor part--up to 15% after 15 years--will become incapable and obtain disablement pension, while 75% of the patients each year are fully capable of work. Within 10 years 50% of the patients will not have experienced any year with impaired capacity for work.
Activities of Daily Living↗
Course of ulcerative colitis: analysis of changes in disease activity over years.
BACKGROUND/AIMS: The course and prognosis of ulcerative colitis (UC) are often reported in terms of mortality and cancer risk. This study examined the clinical course in terms of morbidity. METHODS: A total of 1161 patients with UC were followed up from diagnosis up to 25 years. Actuarial analysis and Markov chain analysis were used to estimate the probabilities of remission and relapses during the disease course. RESULTS: The distribution of disease activity was remarkably constant each year, with about 50% of patients in clinical remission. After 10 years, the colectomy rate was 24%. The cumulative probability of a relapsing course is 90% after 25 years of follow-up. The course of disease changed between remission and relapse without significant predictors, except for disease activity in foregoing years. In years 3-7 after diagnosis, 25% of patients were in remission; 18% had activity every year; and 57% had intermittent relapses. Activity in the first 2 years after diagnosis significantly correlated with having an increased probability of 5 consecutive years of disease activity (P = 0.00001). The probability of maintaining working capacity after 10 years was 92.8% (range, 90.8%-94.8%). CONCLUSIONS: About half of patients with UC will be in remission at any time, although 90% have an intermittent course. Relapses are unpredictable except that disease activity in foregoing years indicates with 70%-80% probability that the disease will continue the following year. Although UC is troublesome, most patients' lives are relatively little influenced by it.
Adolescent↗
Intestinal permeability in patients with Crohn's disease and ulcerative colitis and their first degree relatives.
Increased intestinal permeability in patients with Crohn's disease and their first degree relatives has been proposed as an aetiological factor. The nine hour overnight urinary excretion of polyethyleneglycol-400 (PEG-400) and three inert sugars (lactulose, l-rhamnose, and mannitol) was used to test the permeation in 47 patients with Crohn's disease of whom 18 had at least one first degree relative with inflammatory bowel disease (2BD) and 52 patients with ulcerative colitis of whom 16 had at least one first degree relative with IBD. A total of 17 first degree relatives with IBD and 56 healthy first degree relatives were included. Thirty one healthy subjects not related to patients with IBD served as controls. No significant differences in PEG-400 permeation were found between the groups of patients, relatives, and controls, or between diseased and healthy relatives. The permeability to lactulose, rhamnose, and mannitol similarly did not differ between the three groups. This study challenges the previously reported findings of increased PEG-400 permeation in patients with Crohn's disease and in their healthy and diseased first degree relatives. There was no increase in permeability in a similar group of ulcerative colitis patients and their families.
Adolescent↗
Frequency of glucocorticoid resistance and dependency in Crohn's disease.
The outcome of the first steroid treatment course was prospectively studied in a regional cohort of 196 patients with Crohn's disease diagnosed 1979-1987. The immediate outcome after 30 days, and the prolonged outcome 30 days after treatment had stopped, are described. In all 109 patients treatment was analysed. Complete remission was obtained in 48%, partial remission in 32%, and no response in 20% within 30 days of treatment. Among primary responders (complete and partial remission), 55% remained in prolonged response after treatment had finished, while 45% relapsed or could not be withdrawn from treatment within one year. Localisation of disease, age, sex or clinical symptoms did not significantly correlate with outcome, which can be summarised as prolonged steroid response in 44%, steroid dependency in 36%, and steroid resistant in 20% of the patients.
Adolescent↗
Mycobacterium paratuberculosis in intestinal tissue from patients with Crohn's disease demonstrated by a nested primer polymerase chain reaction.
BACKGROUND: The etiology of Crohn's disease remains unknown, but current research has concentrated on autoimmunity and/or mycobacterial infection. The polymerase chain reaction (PCR) enables the detection of genetic material even when very few microorganisms are present. METHODS: A nested primer PCR for detection of a multi-copy insertional element (IS900) specific for Mycobacterium paratuberculosis was applied to DNA extracted from fresh and from paraffin-embedded intestinal tissue obtained from patients undergoing surgery. RESULTS: In fresh intestinal tissue from 11 of 24 patients with Crohn's disease, from 2 of 10 patients with ulcerative colitis, and from 3 of 28 patients with other colonic disorders, specific M. paratuberculosis DNA was found. In paraffin-embedded Crohn's disease tissue the presence of specific M. paratuberculosis DNA was also increased. CONCLUSIONS: Whether the presence of M. paratuberculosis is connected to the inflammatory bowel disease or is a mere coincidence cannot be stated. We find this presence interesting and encouraging for further investigations.
Adolescent↗
[Long-term prognosis of patients with ulcerative colitis].
A regional inception cohort of 1161 ulcerative colitis patients was followed from diagnosis to the end of 1987. Follow-up rate for death and occurrence of cancer was 99.9%. Median observation time 11.7 years, range 0-26 years. One hundred and forty-one deaths were observed, 26 due to ulcerative colitis or complications thereof. No significant excess mortality was found after the first year, but in the year of diagnosis the relative risk of death was 2.4 (p < 0.001). The cumulative colectomy rate was 32.4% 25 years after diagnosis. The initial extent of disease significantly influenced the colectomy probability, being 35% in total colitis, 19% in substantial colitis and 9% in distal colitis within the first five years after diagnosis. Six patients developed colorectal cancer within the observation period. Compared to the expected number of 6.6 the relative risk for patients with ulcerative colitis was 0.9. The calculated cumulative cancer incidence was 3.1% after 25 years (95% confidence limits 0.0-6.8). The calculated lifetime risk (0 to 74 years) for development of colorectal cancer was 3.5% for the patients compared to 3.7% for the Danish population. We conclude that with an active approach to medical and surgical treatment as was practiced here, those patients who are left with their colon intact bear no significantly increased risk of colo-rectal malignancy.
Adolescent↗
[Increased incidence of Crohn disease in the county of Copenhagen].
The incidence of Crohn's disease was assessed in a population based study in Copenhagen County from 1962-1987. The incidence increased six fold during the study period from 0.62/10(5) in 1962 to a mean of 4.1/10(5) from 1979-1987, equally in both sexes. The highest incidence was found in the age group 15-24 years: 12.8/10(5) for women and 6.0/10(5) for men (as mean of the period 1979-1987). The prevalence at the end of the study was 54/10(5). The clinical symptoms and extent of disease at diagnosis did not change over the time, but a significantly higher disease activity was found in the 1980's, 74% (1962-1979) vs 84% (1980-1987), p = 0.04. The increase in incidence of Crohn's disease is well established in most parts of the industrialized world. The analysis shows that it is not due to a new disease entity, since the extent of disease, the age and sex distribution, and the symptoms remained unchanged during the 26 year study period.
Adolescent↗
[Treatment of travelers' diarrhea].
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Diarrhea↗
Investigation of inheritance of chronic inflammatory bowel diseases by complex segregation analysis.
OBJECTIVE: To investigate the mode of inheritance of ulcerative colitis and Crohn's disease by complex segregation analysis. DESIGN: Cross sectional population based survey of familial occurrence of chronic inflammatory bowel disease. SETTING: Population of the Copenhagen county in 1987. SUBJECTS: 662 patients in whom inflammatory bowel disease had been diagnosed before 1979, of whom 637 (96%) provided adequate information. Of 504 patients with ulcerative colitis, 54 had 77 relatives with ulcerative colitis and of 133 patients with Crohn's disease, five had seven relatives with Crohn's disease. MAIN OUTCOME MEASURES: Patterns of segregation of either disease as assessed by complex segregation analysis performed with the computer program POINTER. RESULTS: The analysis suggested that a major dominant gene with a penetrance of 0.20-0.26 is present in 9-13% of adult patients with ulcerative colitis. The analysis did not allow for other components in the familial aggregation. For Crohn's disease the best fitting model included a major recessive gene with complete penetrance, for which 7% of the patients are homozygous. However, this model was not significantly different from a multifactorial model. CONCLUSIONS: The segregation pattern indicates that a major dominant gene has a role in ulcerative colitis, and suggests that a major recessive gene has a role in Crohn's disease.
Adolescent↗
Intestinal cancer risk and mortality in patients with Crohn's disease.
BACKGROUND: It is important to know about mortality, risk of intestinal cancer, and surgical intervention as well as possible predictive factors for patients with Crohn's disease. These prognostic parameters were estimated by regular follow-up of a complete, regional incidence cohort of 373 patients. METHODS: Annual assessments of clinical conditions were the basis for statistical evaluation with life table analysis, calculations of relative risk, and lifetime cancer risk. RESULTS: Survival curves for the total group of patients with Crohn's disease and the background population did not differ. However, a subgroup of patients aged 20-29 years at diagnosis (P = 0.04) and a subgroup of patients with extensive small bowel disease (P = 0.03) showed slightly increased mortality within the first 5 years. Cancer in small and/or large bowel occurred in 3 patients vs. an expected 1.8(P = NS). Small bowel cancer was found in 2 patients vs. the 0.04 expected (P = 0.001). Lifetime risk of intestinal cancer was 4.1% compared with 3.8% for the Danish population in general (P = NS). Probability of surgical resection within 15 years after diagnosis was 70%. The initial extent of disease significantly influenced the probability for resection, which was 78% in ileocecal enteritis and 44% in all other localizations within 5 years after diagnosis. CONCLUSIONS: The overall mortality and life-time risk of cancer in patients with Crohn's disease was not found increased, although the risk of rare small bowel cancer was significantly increased.
Adolescent↗
Colorectal cancer risk and mortality in patients with ulcerative colitis.
A regional inception cohort of 1161 ulcerative colitis (UC) patients was followed up from diagnosis to the end of 1987. The follow-up rate for death and occurrence of cancer was 99.9% (median observation time, 11.7 years; range, 0-26 years). One hundred forty-one deaths were observed, 26 caused by UC or complications thereof. No significant excess mortality was found after the first year, but in the year of diagnosis the relative risk of death was 2.4 (P < 0.001). The cumulative colectomy rate 25 years after diagnosis was 32.4%. The initial extent of disease significantly influenced the colectomy probability, being 35% in total colitis, 19% in substantial colitis, and 9% in distal colitis within the first 5 years after diagnosis. Six patients developed colorectal cancer within the observation period. Compared with the expected number of 6.6, the relative risk for patients with UC was 0.9. The calculated cumulative cancer incidence was 3.1% after 25 years (95% confidence limits, 0.0-6.8). The calculated lifetime risk (0-74 years) for development of colorectal cancer was 3.5% for UC patients compared with 3.7% for the Danish population. It is concluded that with an active approach to medical and surgical treatment, as practiced here, patients whose colons are left intact bear no significantly increased risk of colorectal malignancy.
Adolescent↗
Treatment of Crohn's disease with fusidic acid: an antibiotic with immunosuppressive properties similar to cyclosporin.
Fusidic acid is an antibiotic with T-cell specific immunosuppressive effects similar to those of cyclosporin. Because of the need for the development of new treatments for Crohn's disease, a pilot study was undertaken to estimate the pharmacodynamics and tolerability of fusidic acid treatment in chronic active, therapy-resistant patients. Eight Crohn's disease patients were included. Fusidic acid was administered orally in a dose of 500 mg t.d.s. and the treatment was planned to last 8 weeks. The disease activity was primarily measured by a modified individual grading score. Five of 8 patients (63%) improved during fusidic acid treatment: 3 at two weeks and 2 after four weeks. There were no serious clinical side effects, but dose reduction was required in two patients because of nausea. Biochemically, an increase in alkaline phosphatases was noted in 5 of 8 cases (63%), and the greatest increases were seen in those who had elevated levels prior to treatment. All reversed to pre-treatment levels after cessation of treatment. The results of this pilot study suggest that fusidic acid may be of benefit in selected chronic active Crohn's disease patients in whom conventional treatment is ineffective. Because there seems to exist a scientific rationale for the use of fusidic acid at the cytokine level in inflammatory bowel disease, we suggest that the role of this treatment should be further investigated.
Adolescent↗
Leucocyte scintigraphy to localize inflammatory activity in ulcerative colitis and Crohn's disease.
The validity of using autologous leucocytes labelled with technetium -99m hexamethyl-propyleneamine-oxine (Tc-HMPAO) for scintigraphy in inflammatory bowel disease was evaluated in 12 patients with clinically active ulcerative colitis (UC) and 10 with Crohn's disease (CD). Colonoscopy and biopsy were used as reference. Scintigrams taken 1 h and 3 h after leucocyte reinjection were evaluated blindly by two independent observer groups. Full agreement was found in 11 of 12 UC patients when compared with colonoscopy but in only 3 of 10 CD patients. Segments with agreement in CD patients often showed neutrophilic granulocyte infiltration at biopsy. The judgements of clinicians and physiologists differed for only 2 of totally 70 UC segments but for 13 of 59 CD segments (kappa, 0.94 and 0.52). It is concluded that Tc-HMPAO scintigraphy might be an alternative to colonoscopy in the control of disease extent in UC. In CD patients the technique might warn about infections complications.
Adult↗
Incidence and prevalence of Crohn's disease in the county of Copenhagen, 1962-87: a sixfold increase in incidence.
The incidence of Crohn's disease increased sixfold from 1962 to 1987 in the county of Copenhagen. The mean annual incidence for 1979-87 was 4.1 per 10(5) inhabitants. The increase was found equally in both sexes, with an approximately 40% higher incidence in women. The maximal incidence was found in the 15- to 24-year age group, being 12.8 per 10(5) per year for women and 6.0 per 10(5) per year for men, as mean of the period 1979-87. The prevalence at the end of the study was 54 per 10(5) inhabitants, 46 per 10(5) in men and 63 per 10(5) in women. The clinical appearance of the disease at the time of diagnosis was remarkably similar during the study period with regard to both the localization of disease and the clinical symptoms and signs. A slightly higher percentage of the patients, however, were in high disease activity at diagnosis in the later years of the study.
Adolescent↗
Familial occurrence of inflammatory bowel disease.
BACKGROUND AND METHODS: We assessed the familial occurrence of inflammatory bowel disease in Copenhagen County, where there has been a long-term interest in the epidemiology of such disorders. In 1987 we interviewed 662 patients in whom inflammatory bowel disease had been diagnosed before 1979, asking whether their first- and second-degree relatives had this disorder. Ninety-six percent of the patients (504 with ulcerative colitis and 133 with Crohn's disease) provided adequate information. RESULTS: As compared with the general population, the first-degree relatives of the 637 patients with ulcerative colitis or Crohn's disease had a 10-fold increase in the risk of having the same disease as the patients, after standardization for age and sex. The risk of having the other of the two diseases was also increased, but less so, and the increase in the risk of having Crohn's disease was not significant in the relatives of patients with ulcerative colitis. The risk of ulcerative colitis in first-degree relatives of patients with ulcerative colitis appeared to be virtually independent of the generation to which the first-degree relative belonged and of the sex of the patient and the relative. The risk of ulcerative colitis in first-degree relatives tended to be higher if the disease had been diagnosed in the patient before the age of 50, but the risk seemed to be independent of the current age of the relatives. The prevalence of the same disease as that of the patient (either ulcerative colitis or Crohn's disease) among second-degree relatives was increased; the prevalence of the other disease was not increased. CONCLUSIONS: The 10-fold increase in the familial risk of ulcerative colitis and Crohn's disease strongly suggests that these disorders have a genetic cause.
Adult↗