Change of diagnosis during the first five years after onset of inflammatory bowel disease: Results of a prospective follow-up study (the IBSEN Study)

Objective. An exact diagnosis of inflammatory bowel disease (IBD) and further subclassification may be difficult even after clinical, radiological and histological examinations. A correct subclassification is important for the success of both medical and surgical therapeutic strategies, but there is a dearth of information available on the frequency of changes in diagnosis in population-based studies. The objective of this work was prospectively to re-evaluate the diagnosis in an unselected cohort of IBD patients during the first five years after the initial diagnosis. Material and methods. Patients classified as IBD or possible IBD in the period 1990–94 (the IBSEN cohort) had their diagnosis re-evaluated after 1 and 5 years. Initially, the patients were classified as ulcerative colitis (UC), Crohn's disease (CD), indeterminate colitis (IC) or possible IBD. At the 5-year visit, patients were classified as UC, CD or non-IBD. Results. A total of 843 patients (518 UC, 221 CD, 40 IC and 64 possible IBD) were identified. Clinical information was available for 94% of the patients who survived after 5 years. A change in diagnosis was found in 9% of the patients initially classified as UC or CD. A change to non-IBD was more frequent than a change between UC and CD. A large proportion of patients initially classified as IC or possible IBD were diagnosed as non-IBD after 5 years (22.5% versus 50%). When IBD was confirmed in these groups, UC was more frequent than CD. Two changes in diagnosis during follow-up were observed in 2.8% of the patients; this was more frequent in patients initially classified as IC or possible IBD. Conclusions. There are obvious diagnostic problems in a minority of patients with IBD; a systematic follow-up is therefore important in these patients.     

Effects of secretin infusion on myocardial performance and metabolism in the dog

The effects of pharmacological doses of secretin were studied in closed-chest, pentobarbital anesthetized dogs. Infusion of secretin 16 clinical units (CU)/kg-h caused a rise in cardiac output (p less than 0.01), peak first derivative of the left ventricular pressure (p less than 0.01), and heart rate (p less than 0.01) and a fall in systemic arteriolar resistance (p less than 0.01) and left ventricular end-diastolic pressure (p less than 0.01). Stroke volume did not change significantly. Myocardial blood flow and oxygen consumption were unchanged. Secretin caused reductions in arterial lactate (p less than 0.01) and glucose (p less than 0.05) concentrations, and arterial concentrations of free fatty acids and insulin were unaltered. There was no change in myocardial uptake of lactate, glucose, or FFA. Secretin 64 CU/kg-h infused in two dogs caused further changes of the hemodynamic variables. Thus, secretin enhances left ventricular function in intact anesthetized dog by combined vasodilating, inotropic, and chronotropic effects, without changing myocardial oxygen or substrate uptake.     

The marked reduction in mixed venous oxygen saturation during early mobilization after cardiac surgery: the effect of posture or exercise?

Early mobilization after cardiac surgery induces a marked reduction in mixed venous oxygen saturation (Svo2). Using pulmonary artery catheters and indirect calorimetry, we investigated the effects of exercise and postural change on cardiac index (CI) and Svo2 before and on the first morning after coronary artery bypass surgery. Sixteen patients with an ejection fraction >0.50 were studied at rest, during supine bicycle exercise, and during passive standing. Supine cycling at 30 W increased CI by 1.5 +/- 0.8 L x min(-1) x m(-2) before and 0.9 +/- 0.7 L x min(-1) x m(-2) after surgery (P < 0.05), whereas Svo2 was reduced from 80% +/- 4% at rest to 63 +/- 6% preoperatively (P < 0.05) and from 71% +/- 5% to 46% +/- 11% postoperatively (P < 0.05). Passive standing reduced CI by 0.8 +/- 0.5 L x min(-1) x m(-2) before and 0.3 +/- 0.4 L x min(-1) x m(-2) after surgery (P < 0.05). Svo2 was reduced from 79% +/- 5% to 64% +/- 7% preoperatively (P < 0.05) and from 72% +/- 6% to 60% +/- 6% postoperatively (P < 0.05). The exercise challenge revealed an altered cardiovascular response after surgery, causing a larger reduction in Svo2 for the same workload. Passive standing significantly reduced Svo2 both days, but this effect was less pronounced after surgery. The response to postural change and exercise was altered after surgery and may both contribute to the reduction in Svo2 during postoperative mobilization.     

Ulcerative colitis and clinical course: results of a 5-year population-based follow-up study (the IBSEN study)

BACKGROUND: The majority of studies concerning the clinical course and prognosis in ulcerative colitis (UC) are old, retrospective in design, or hospital based. We aimed to identify clinical course and prognosis in a prospective, population-based follow-up study MATERIALS AND METHODS: Patients diagnosed with inflammatory bowel disease (IBD) or possible IBD in southeastern Norway during the period 1990-1994 were followed prospectively for 5 years. The evaluation at 5 years included an interview, clinical examination, laboratory tests, and colonoscopy. RESULTS: Of 843 patients diagnosed with IBD, 454 patients who had definite UC and for whom there were sufficient data for analysis were alive 5 years after inclusion in the study. The frequency of colectomy in this population was 7.5%. Forty-one percent of the patients were not taking any kind of medication for IBD at 5 years. Of the patients initially diagnosed with proctitis, 28% had progressed during the observation period, 10% to extensive colitis. The majority of the patients (57%) had no intestinal symptoms at 5 years, and only a minority (7%) had symptoms that interfered with everyday activities. Among the patients who underwent colonoscopy at the 5-year visit, symptoms were frequently reported in patients without macroscopic inflammation (44%). A relapse-free course was observed in 22% of the patients. A decrease in symptoms during the follow-up period was the most frequent course taken by the disease and was observed in 59% of the cases. The extent of disease was unrelated to symptoms at 5 years and also to relapse rate and course of disease during the 5-year period. CONCLUSIONS: The disease course and prognosis of UC appears better than previously described in the literature. The frequency of surgery was low, and only a minority of the patients had symptoms that interfered with their everyday activities 5 years after diagnosis.     

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.     

An entirely specific type I A-kinase anchoring protein that can sequester two molecules of protein kinase A at mitochondria

A-kinase anchoring proteins (AKAPs) tether the cAMP-dependent protein kinase (PKA) to intracellular sites where they preferentially phosphorylate target substrates. Most AKAPs exhibit nanomolar affinity for the regulatory (RII) subunit of the type II PKA holoenzyme, whereas dual-specificity anchoring proteins also bind the type I (RI) regulatory subunit of PKA with 10-100-fold lower affinity. A range of cellular, biochemical, biophysical, and genetic approaches comprehensively establish that sphingosine kinase interacting protein (SKIP) is a truly type I-specific AKAP. Mapping studies located anchoring sites between residues 925-949 and 1,140-1,175 of SKIP that bind RI with dissociation constants of 73 and 774 nM, respectively. Molecular modeling and site-directed mutagenesis approaches identify Phe 929 and Tyr 1,151 as RI-selective binding determinants in each anchoring site. SKIP complexes exist in different states of RI-occupancy as single-molecule pull-down photobleaching experiments show that 41 ± 10% of SKIP sequesters two YFP-RI dimers, whereas 59 ± 10% of the anchoring protein binds a single YFP-RI dimer. Imaging, proteomic analysis, and subcellular fractionation experiments reveal that SKIP is enriched at the inner mitochondrial membrane where it associates with a prominent PKA substrate, the coiled-coil helix protein ChChd3.     

Cytokine Levels After Consumption of a Medicinal Agaricus blazei Murill‐Based Mushroom Extract,AndoSan™, in Patients with Crohn's Disease and Ulcerative Colitis in a Randomized Single‐Blinded Placebo‐Controlled Study

Ingestion of the Agaricus blazei Murill‐based mushroom extract AndoSan^? has been shown in randomized placebo‐controlled studies to improve symptoms in Crohn's disease (CD) and ulcerative colitis (UC) and also fatigue and quality of life in the latter patients. The aim was to examine whether this clinical impact of AndoSan^? intake could be explained by influence on foremost pro‐inflammatory cytokines in the patients. Fifty patients with symptomatic UC and CD were randomized and blinded for oral daily intake of AndoSan^? or placebo. Blood samples taken before (visit 1) and after 21 days’ (visit 3) consumption were analysed for cytokines IL‐1ß, IL‐2, IL‐4‐8, IL‐10, IL‐12‐13, IL‐17, G‐CSF, GM‐CSF, IFN‐γ, MCP‐1, MIP‐1ß and TNF‐α. Baseline cytokine levels were similar in CD and UC. In CD, cytokine levels at visit 1 versus visit 3 were unaltered within the AndoSan^? and the placebo groups. Only IL‐2 was significantly reduced at visit 3 in the Andosan^? compared with the placebo group. However, when combining IL‐1ß, IL‐6 and G‐CSF in the patients with CD, the cytokine levels were significantly lower in the AndoSan^TM ‐ versus the placebo group, visit 3. In UC, levels of IL‐2, IL‐5 and MIP‐1ß were reduced within the AndoSan^? group. IL‐5 was also reduced at visit 3 compared with placebo. Generally, the effect on reduction in systemic cytokine levels by consumption of AndoSan^? was limited and supported only marginally anti‐inflammatory effects in these patients. Therefore, other explanations behind the clinical anti‐inflammatory effects than the contribution of cytokines seem more pertinent, including anti‐allergic and antioxidant activities.     

Balance and gait improved in patients with MS after physiotherapy based on the Bobath concept

Background and Purpose . Patients with multiple sclerosis (MS) tend to have movement difficulties, and the effect of physiotherapy for this group of patients has been subjected to limited systematic research. In the present study physiotherapy based on the Bobath concept, applied to MS patients with balance and gait problems, was evaluated. The ability of different functional tests to demonstrate change was evaluated. Method . A single‐subject experimental study design with ABAA phases was used, and two patients with relapsing–remitting MS in stable phase were treated. Tests were performed 12 times, three at each phase: A (at baseline); B (during treatment); A (immediately after treatment); and A (after two months). The key feature of treatment was facilitation of postural activity and selective control of movement. Several performance and self‐report measures and interviews were used. Results . After intervention, improved balance was shown by the Berg Balance Scale (BBS) in both patients, and improved quality of gait was indicated by the Rivermead Visual Gait Assessment (RVGA). The patients also reported improved balance and gait function in the interviews and scored their condition as ‘much improved’. Gait parameters, recorded by an electronic walkway, changed, but differently in the two patients. Among the physical performance tests the BBS and the RVGA demonstrated the highest change, while no or minimal change was demonstrated by the Rivermead Mobility Index (RMI) and Ratings of Perceived Exertion (RPE). Conclusion . The findings indicate that balance and gait can be improved after physiotherapy based on the Bobath concept, but this should be further evaluated in larger controlled trials of patients with MS. Copyright © 2006 John Wiley & Sons, Ltd.     

Gastrointestinal peptides in serum and synovial fluid from patients with inflammatory joint disease.

The concentrations of immunoreactive vasoactive intestinal polypeptide (ir-VIP), immunoreactive pancreatic polypeptide (ir-PP), ir-somatostatin, and ir-secretin were measured in serum and synovial fluid from patients suffering from various inflammatory joint diseases. One group of patients were not taking any medication, while another group received anti-inflammatory treatment at the time of sampling. High levels of ir-VIP in the synovial fluid were observed in the untreated group of patients, and the concentration of ir-VIP in the synovial fluid was significantly higher than in parallel serum samples. On the other hand, no significant differences in the concentrations of the other peptides were observed either between serum and synovial fluid or between the two groups of patients. It is suggested that VIP is released locally at the inflammatory site and that VIP may be of significance in inflammatory disorders.     

Plasma cholecystokinin (CCK) before and after a jejunoileal bypass operation in obese patients with reference to appetite regulation

Plasma cholecystokinin (CCK) rose significantly after a 15-min liquid test meal in six normal controls and six obese patients, both before and after a jejunoileal bypass operation. Post-prandial rises in the obese patients were virtually unaffected by the operation, and tended to be higher in the obese patients than in the normal controls. It is therefore concluded that hormonal CCK is unlikely to be a mediator of satiety signals from the digestive tract in obese persons.