C-reactive protein: a predictive factor and marker of inflammation in inflammatory bowel disease. Results from a prospective population-based study.

BACKGROUND AND AIMS: C-reactive protein (CRP) levels are often used in the follow-up of patients with inflammatory bowel disease (IBD). The aims of this study were to establish the relationship of CRP levels to disease extent in patients with ulcerative colitis and to phenotype in patients with Crohn's disease, and to investigate the predictive value of CRP levels for disease outcome. METHODS: CRP was measured at diagnosis and after 1 and 5 years in patients diagnosed with IBD in south-eastern Norway. After 5 years, 454 patients with ulcerative colitis and 200 with Crohn's disease were alive and provided sufficient data for analysis. RESULTS: Patients with Crohn's disease had a stronger CRP response than did those with ulcerative colitis. In patients with ulcerative colitis, CRP levels at diagnosis increased with increasing extent of disease. No differences in CRP levels at diagnosis were found between subgroups of patients with Crohn's disease as defined according to the Vienna classification. In patients with ulcerative colitis with extensive colitis, CRP levels above 23 mg/l at diagnosis predicted an increased risk of surgery (odds ratio (OR) 4.8, 95% confidence interval (CI) 1.5 to 15.1, p = 0.02). In patients with ulcerative colitis, CRP levels above 10 mg/l after 1 year predicted an increased risk of surgery during the subsequent 4 years (OR 3.0, 95% CI 1.1 to 7.8, p = 0.02). A significant association between CRP levels at diagnosis and risk of surgery was found in patients with Crohn's disease and terminal ileitis (L1), and the risk increased when CRP levels were above 53 mg/l in this subgroup (OR 6.0, 95% CI 1.1 to 31.9, p = 0.03). CONCLUSIONS: CRP levels at diagnosis were related to the extent of disease in patients with ulcerative colitis. Phenotype had no influence on CRP levels in patients with Crohn's disease. CRP is a predictor of surgery in subgroups of patients with either ulcerative colitis or Crohn's disease.

Health-related quality of life in patients with inflammatory bowel disease five years after the initial diagnosis.

BACKGROUND: Health-related quality of life (HRQOL) has become an important tool in evaluating patient satisfaction in inflammatory bowel disease (IBD). So far, few prospective follow-up studies have been done to identify variables that influence HRQOL. We aimed to identify demographic and clinical variables that influence HRQOL 5 years after diagnosis in patients with ulcerative colitis (UC) or Crohn disease (CD) included in a prospective follow-up study from 1990 to 1994 (the IBSEN study). METHODS: All patients completed the Inflammatory Bowel Disease Questionnaire (IBDQ), a disease-specific quality-of-life questionnaire translated into Norwegian and validated. We present data from 497 patients (328 UC patients and 169 CD patients, mean age 43.3 years, 48% female). The impact of age, gender, smoking, symptom severity, disease distribution, rheumatic symptoms and surgery on IBD patients' HRQOL was analysed. RESULTS: Women had a reduction in IBDQ total score of 10 points compared to men, CD patients had a reduction of 7.5 compared to UC patients. The patients with moderate/severe symptoms had a 50 points lower score than the patients without symptoms. The patients with rheumatic symptoms had a 10 points lower total score than the patients without these symptoms. All differences were statistically significant. The multiple regression analysis showed that symptom severity, rheumatic symptoms and female gender were the strongest predictors of reduction in HRQOL for both diagnosis groups. CONCLUSION: IBD symptoms, rheumatic symptoms and female gender have a significant influence on patients' HRQOL as measured by IBDQ. This was confirmed by the regression analysis.

Screening of first degree relatives of patients operated for colorectal cancer: evaluation of fecal calprotectin vs. hemoccult II.

UNLABELLED: Fecal calprotectin (CPT) is elevated in the majority of patients with known colorectal cancer (CRC), but the specificity is not clarified. AIM: To evaluate if a CPT test (PhiCal ELISA) was more sensitive than Hemoccult II test in detecting colorectal neoplasia, and to obtain reference values in subjects with normal colonoscopy. To evaluate a possible relation between number and extent of dysplasia of adenomas in first degree relatives of patients with CRC and the stage of the carcinoma in the index casus. Further to study the prevalence of CRC and adenomas in the first degree relatives of patients operated for CRC. METHOD: In a multicenter study, 253 first degree relatives of patients with CRC, aged 50-75 years (mean age 60 years) underwent colonoscopy after having delivered stool samples and three Hemoccult II slides. RESULTS: In 237 first degree relatives from 148 patients with CRC, polyps were found in 118 (50%). Seventy three (31%) had adenomas and 17 had adenomas > or =10 mm. Five had asymptomatic cancers. The specificity of fecal CPT for adenomas at cut off levels 15 mg/l. The sensitivity of Hemoccult II for adenomas was 8%, and 4/5 of patients with carcinoma had negative Hemoccult II. The specificity for adenomas was 95%. CONCLUSION: Fecal CPT test was more sensitive than Hemoccult II in detecting colorectal neoplasia but the specificity was lower. In a high risk group like first degree relatives of patients with CRC, there are good reasons to consider fecal CPT as a first test in selecting patients for endoscopy.

[Esophageal lesions associated with diphosphonates]. / Oesophagusskader relatert til bisfosfonater.

BACKGROUND: Bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption and effective in preventing osteoporotic fractures, but they can occasionally cause oesophageal adverse events. MATERIAL AND METHODS: We report on seven patients who developed severe oesophagitis or oesophageal ulceration during treatment with bisphosphonates. They were registered at our endoscopy unit during a 31-month period. RESULTS: Six of the patients took alendronate (Fosamax) and one etidronate (Didronate). The oesophageal lesions heal on discontinuation of the bisphosphonate. Institution of gastric acid suppression treatment may enhance the healing process. INTERPRETATION: In order to minimise the risk of serious side-effects, it is important to give detailed instructions regarding medication and to ensure that the instructions are properly understood. The risk of serious complications can be reduced by early recognition of oesophageal symptoms and appropriate intervention.

Clinical course during the 1st year after diagnosis in ulcerative colitis and Crohn's disease. Results of a large, prospective population-based study in southeastern Norway, 1990-93.

BACKGROUND: The clinical course and prognosis in ulcerative colitis (UC) and Crohn's disease (CD) have been described in many studies, mostly retrospective. Such studies are hampered by problems such as inclusion over a long time period, proper definitions, incomplete case records, and outdated methods of diagnosis. In a prospective study we identified 846 patients with inflammatory bowel disease (IBD) over a 4-year period from 1990 to 1993. Uniform diagnostic and therapeutic strategies were used as a basis for later assessment of the short-term clinical course in different subgroups of UC and CD and analysis of potential risk factors for relapse or surgery. METHODS: At the time of follow-up, a mean of 16.2 months after diagnosis, 496 UC patients and 232 CD patients, altogether 98%, were available for evaluation. A colonoscopy was performed in 88% (410 of 465) of the UC patients attending a clinical examination and in 76% (164 of 216) of the CD patients. RESULTS: Eleven patients with UC and five patients with CD died during follow-up, four of complications related to IBD. The cumulative 1-year relapse rate in the remaining patients was 50% for UC and 47% for CD. Of the patients with relapses 11 % of the UC patients and 10% of the CD patients had a chronic relapsing course without any difference with regard to the various disease categories in UC or CD. An increased risk of relapse was found in patients less than 50 years old only in UC. In UC a higher risk for surgery was found in patients with extensive colitis compared with left-sided colitis (P = 0.011), and CD patients with small-bowel involvement had a higher risk of surgery than patients with disease confined to the colon (P = 0.021). There was no excess risk of relapse or surgery in smokers as compared with non-smokers or former smokers, nor did the risk of relapse vary with the level of cigarette consumption in either UC or CD patients. CONCLUSION: The high relapse rate of around 50% for both UC and CD calls for a review of the existing treatment. Further follow-up will be necessary to improve our ability to make clinical decisions relating to medical and surgical treatment options.

Inflammatory bowel disease: re-evaluation of the diagnosis in a prospective population based study in south eastern Norway.

BACKGROUND: The incidence figures for ulcerative colitis (UC) and Crohn's disease (CD) have been difficult to interpret, and geographical variations may be due to differences in classification criteria and study design. Few studies have based the incidence on prospective systematic follow up to confirm the initial diagnosis. METHODS: Between 1990 and 1993, in a prospective incidence study of inflammatory bowel disease (IBD) in south eastern Norway, 527 cases of UC, 228 cases of CD, 36 cases of indeterminate colitis (IND), and 55 cases of possible IBD were identified, yielding an annual incidence of 13.6, 5.9, 0.9, and 1.4 per 10(5) respectively. The diagnosis and all clinical data were reviewed by two gastroenterologists independently of each other. One to two years after diagnosis, all patients were offered a clinical follow up in which the initial diagnosis was assessed. RESULTS: Between the time of diagnosis and the follow up, 16 patients had died, four of complications related to IBD. Of the remaining 830 patients, 98% (814/830) were available for follow up, 93% (772/830) attended a clinical examination which included a colonoscopy in 77% (637/830), and the remainder had had a telephone interview, or reassessment based on hospital records, or both. Twenty seven patients were reclassified as not having IBD (3%), and 65 patients were characterised as possible IBD (8%). Of the patients initially classified as UC, 88% had their diagnosis confirmed, compared with 91% with an initial diagnosis of CD. In patients with indeterminate colitis, 33% were classified as definite UC and 17% as CD. This reclassification of patients yielded a corrected annual incidence of 12.8 for UC and 6.0 for CD. CONCLUSION: At follow up one to two years after the diagnosis of IBD, the initial incidence was only marginally altered. This is probably due to uniform inclusion criteria and careful diagnostic methods. The study also illustrates the importance of the re-evaluation of the initial diagnosis as close to 10%, both among patients with UC and CD, were reclassified at follow up.

[Ischemic colitis in young patients]. / Iskemisk kolitt hos yngre pasienter.

Ischaemic colitis is an established clinical entity in the elderly, characterized by acute onset of abdominal pain, diarrhoea and rectal bleeding. Six women 20-49 years old have been admitted to our hospital with ischaemic colitis during the last seven years. One of the cases in described, followed by a discussion of associated factors and clinical aspects. We emphasize that ischaemic colitis is an important differential diagnosis of colitis even in younger patients.

Incidence of Crohn's disease in four counties in southeastern Norway, 1990-93. A prospective population-based study. The Inflammatory Bowel South-Eastern Norway (IBSEN) Study Group of Gastroenterologists.

BACKGROUND: Standardized criteria for Crohn's disease (CD) have only recently been developed, and prospective community-based incidence studies have been performed only during the past 3 decades. Geographic variations in incidence may therefore be due to differences in study design. METHODS: From 1 January 1990 to 31 December 1993 all new cases of CD in four counties in southeastern Norway were prospectively registered. RESULTS: A total of 225 new cases yielded an annual incidence of 5.8/10(5), with the highest incidence in mixed rural-urban areas. A peak of 11.2/10(5) in the annual incidence was found for the age group 15 to 24 years, with no significant differences in the overall annual incidence by gender. An average duration of 6 months of disease before diagnosis was unchanged during the 4 years. About half of the patients had isolated colonic disease, and one-quarter had isolated small-bowel disease. CONCLUSIONS: This study confirms the high incidence figures for Scandinavia, with a particularly high incidence in mixed rural-urban areas. Ileocolonoscopy improves the accuracy of the diagnosis and of the determination of disease extent, which may have therapeutic implications for the treatment and follow-up of patients.

Incidence of ulcerative colitis and indeterminate colitis in four counties of southeastern Norway, 1990-93. A prospective population-based study. The Inflammatory Bowel South-Eastern Norway (IBSEN) Study Group of Gastroenterologists.

BACKGROUND: The incidence of ulcerative colitis (UC) has been difficult to interpret because prospective studies have only been performed during the past 3 decades. Geographic variations may therefore be due to differences in study design. METHOD: From 1 January 1990 to 31 December 1993 all new cases of UC in four counties in southeastern Norway were prospectively registered. Cases diagnosed as indeterminate colitis (IND) when endoscopy and histopathology were inconclusive or diverged with regard to diagnosis of UC or Crohn's disease (CD) were also included in the study. RESULTS: A total of 525 cases of UC and 93 cases of IND yielded an mean annual incidence of 13.6/10(5) and 2.4/10(5), respectively. There were differences in incidence between counties, and a peak of 21.5/10(5) in the annual incidence was found for the age group 25 to 34 years in UC. The distribution was about equal for each of the groups proctitis and left-sided and extensive colitis. The time interval from onset of symptoms to diagnosis was 4 months. CONCLUSION: In this study one of the highest incidences of UC in the world has been found. The classification 'indeterminate colitis' seems reasonable to use in some of the cases to prevent misclassification at the initial stage of diagnosis.

[Esophageal lesions induced by iron tablets]. / Jerntablettinduserte oesophaguslesjoner.

Oesophageal injury in the form of ulcers, with deposition of iron salts, was diagnosed histologically in 12 patients over a 3-years period. One patient died following perforation of the oesophagus. Not in any of the patients was the use of iron tablets thought of clinically as a possible cause of the lesion. This appears to be the most likely explanation, however, owing to the fact that the use of iron sulphate tablets of sustained release type was reported by ten out of 12 patients. The patients were all elderly and the majority were bedridden. Any gain from using iron medication in the elderly and bedridden should be weighed against the potential danger related to the use of iron sulphate tablets of sustained release type.

Gastrointestinal bleeding associated with the use of non-steroidal, anti-inflammatory drugs--symptomatology and clinical course.

The symptoms associated with admission for gastrointestinal haemorrhage were studied in relation to the intake of non-steroidal, anti-inflammatory drugs (NSAIDs) within fourteen days prior to admission. In a prospective, two-year study we included only those with bleeding due to gastroduodenal ulcers or haemorrhagic erosive gastritis. In 94 patients with a median age of 74 years, NSAID use was stated in 54, but the symptoms in these subjects (degree of epigastric pain, nausea or heartburn) were no different from those without previous NSAID use. Correspondingly, no difference was seen as to the clinical course of the bleeding.

Gastrointestinal bleeding: dyspeptic symptoms and clinical course in relation to use of non-steroidal antiinflammatory drugs.

To study the symptoms of NSAID-associated gastroduodenal bleeding, 94 patients (median age 71 years, range 19-90), were included in a prospective, clinical trial where hematemesis or melena from gastroduodenal ulceration or haemorrhagic/erosive gastritis were the inclusion criteria. NSAID use within one month was studied in relation to subjective symptoms prior to admission and to clinical course of the episode. Significantly fewer of the NSAID users (n = 54) than the non-users (n = 40) had experienced prior peptic ulceration or dyspeptic symptoms. Otherwise, no differences were seen between users and non-users, as regards pre-admission epigastric pain, heartburn or nausea. Also, the clinical course was similar in the two groups. We also found sporadic and regular NSAID use to be similar in this respect. These data do not support the alleged masking of ulcer symptoms by NSAIDs in bleeding ulcers.

Intracellular regulation of lipoprotein lipase in human monocyte-derived macrophages.

The intracellular pathway of lipoprotein lipase (LPL) has been examined in human monocyte-derived macrophages in culture. These cells were previously shown to synthesize and constitutively secrete LPL. The secretion is dependent on new enzyme synthesis. 6-d-old human monocytes have stores of mRNA for linear release of LPL up to 24 h. Enzyme activity in cells and in culture medium was almost completely inhibited by 24 h treatment with tunicamycin, an inhibitor of glycosylation. In monensin-treated cells a pronounced increase in enzyme activity was found, whereas the secreted activity was markedly reduced. This indicates that LPL in human monocytes is processed through a pH sensitive part of the Golgi complex and that the terminal glycosylation is not needed for the expression of its catalytic activity. Our results suggest that lysosomal function is not important in secretion of the enzyme, whereas vesicular transport seem to be involved in regulating LPL in human monocyte-derived macrophages in culture.

Injection sclerotherapy of bleeding oesophageal and gastric varices in children.

During a 4-year period (1980-1984) nine children aged 11/2 to 13 years with acute or recent bleeding from gastro-oesophageal varices were treated by injection sclerotherapy. Chronic liver disease was the cause of portal hypertension in three and extrahepatic portal venous obstruction in six. Seven had experienced recurrent bleeding episodes, and massive haemorrhage initiated treatment in two children. Seven patients rebled before eradication of all critical varices and two after, both from ulcers at the site of injection. All critical varices were eradicated in the nine children within a median of 11/2 months, after a median of five courses of injections. No further variceal bleeding occurred during the follow-up period of up to 57 months (mean, 20.9 months). Complications included oesophageal and gastric ulcers in four patients. One patient with congenital hepatic fibrosis and aortic insufficiency died of septicaemia 19 months after entering the treatment.

Synthesis and secretion of lipoprotein lipase by human monocyte-derived macrophages.

Human monocytes isolated from either defibrinated blood or buffy coat were shown to produce and secrete lipoprotein lipase during culture. The secretion occurred constitutively. Low levels of enzyme activity in the medium from freshly isolated cells increased with time of incubation, and maximal activity was attained after 9 days. The addition of heparin resulted in a substantial increase of enzyme activity in the culture medium. The optimal concentration of heparin was about 2 U/ml. The production of lipoprotein lipase was dependent on the presence of serum in the culture medium, and the optimal supplementation of serum was 25-50%.

Heparin treatment of deep venous thrombosis in 280 patients: symptoms related to dosage.

280 patients with phlebographically proven deep venous thrombosis received intravenous heparin infusion, mean duration 6.8 days, mean dose 370 U/kg/day. In 58 patients (21%) there was no apparent predisposing factor. Leg pain diminished more rapidly than edema. At discharge, 46% had edema. Symptoms suggesting pulmonary embolism (PE) occurred in 13 patients (4.6%) whose mean daily heparin dose was similar to that of the others. The only fatal PE occurred three days after cessation of heparin administration. Eight patients (3%) experienced major bleeding, the only fatal occurring after thoracocentesis. The frequency of major bleeding in patients above 70 years was 8% in females and 4% in males, in those below 70 years it was 0.5%; 22 patients (8%) had minor bleeding. Control phlebography after one week revealed completely cleared thrombus in 3%, partial clearance in 36%, unchanged in 39% and increased thrombosis in 22%. Dosage was significantly correlated to thrombus resolution.

Injection sclerotherapy of bleeding oesophageal and gastric varices using a flexible endoscope.

Thirteen patients with acute or recent bleeding from gastro-oesophageal varices were treated by sclerotherapy using flexible fiberoptic endoscope. Primary haemostasis was obtained in 10 of 11 admissions with active bleeding. Three patients have been treated for gastric varices with the same method. Such treatment has not been reported before. During the follow-up period, three patients died, two of variceal haemorrhage and one of pneumonia. Ten patients are still alive 2-53 months after the first admission. A total of 117 treatment courses were given, on an average 9 per patient. Complications included superficial mucosal necrosis without clinical consequences in several cases, 3 patients developed oesophageal and gastric ulcers and one moderate oesophageal stenosis. Rebleeding occurred in 4 patients, in 2 of them because of ulcers at the sites of injections.

Localized telangiopathy of the stomach and duodenum diagnosed and treated endoscopically. Case reports and review.

During the period from January, 1976 to December, 1979 we performed 5000 upper gastrointestinal endoscopic examinations. Of these 650 were for gastrointestinal bleeding. In nine patients we found, endoscopically localized mucosal vascular abnormalities of the stomach and duodenum. Repeated endoscopic examinations were necessary in four cases before the correct diagnosis was made. Three telangiopathies (as we prefer to call them) were found incidentally, and in six cases endoscopy was performed because of gastrointestinal bleeding. In five of the six cases with bleeding, the telangiopathy (TAP) probably was the bleeding lesion. The treatment of choice is endoscopic, either by electrodestruction with mono-polar current, or by removal with a diathermy snare. Neither barium meal x-rays of the upper gastrointestinal tract in five cases, nor exploratory laparotomy in two cases, revealed the telangiopathies. There has been no rebleeding after the treatment, except for one case in which another TAP of the small or large bowel is implicated.