Ulcerative colitis in the county of Uppsala 1945-2007: incidence and clinical characteristics.

OBJECTIVE: The incidence of ulcerative colitis has increased in many parts of the world during the second part of the twentieth century. In the county of Uppsala in the middle part of Sweden, the epidemiology of ulcerative colitis has been studied during two different time periods, 1945-1964 and 1965-1983. These figures have now been compared to the present day situation, 2005-2007. METHOD: The incidence figures in the two first studies were the results of retrospective studies but the figures from 2005 to 2007 were generated prospectively. The clinical characteristics during 1945-1964 were described according to the Montreal classification and a comparison between the first and third study periods could therefore be done. RESULTS: During the study period, the population of the county increased from 146000 to 323270 inhabitants. The crude incidence of ulcerative colitis increased from 2 to 19.2 new cases per 100000 inhabitants/year. The age distribution was remarkably stable when the first 20 years was compared with the last 3 years (mean age 36 vs. 38.1 and range 2-84 vs. 3-84) except for those below 11 years of age. CONCLUSION: Between 1945 and 2007 the incidence of UC in the County of Uppsala increased from 2 to 19.2 new cases/100000. The increase affected all age groups except those below 11 years of age.

Clinical trial: the safety and short-term efficacy of recombinant cholera toxin B subunit in the treatment of active Crohn's disease.

BACKGROUND: The cholera toxin B subunit ameliorates experimentally induced colitis in mice. In humans, cholera toxin B subunit has never been tested in the treatment of Crohn's disease (CD). AIM: To evaluate the safety and efficacy of treatment with recombinant cholera toxin B subunit of patients with CD. METHODS: An open-label, multicentre, nonrandomized trial including 15 patients with mild/moderate CD. Patients received an oral solution of 5 mg recombinant cholera toxin B subunit three times weekly for 2 weeks. Reduction in CD Activity Index (CDAI) with >100 between baseline and days 15, 29, 42 and 70 defined clinical response. Patients with CDAI score < or = 150 were defined as being in remission. RESULTS: A significant decrease in CDAI score was observed. Response rates were 40% in the full analysis set and 42% in the per protocol analysis. Two patients receiving adjuvant treatment after day 29 were excluded, after which 40% were in remission at 4 weeks and 30% at 8 weeks post-treatment. Mild side effects (arthralgia, headache and pruritus) were seen in 33% of patients. CONCLUSIONS: Treatment with recombinant cholera toxin B subunit was safe. Approximately 40% of patients with active CD responded to treatment. Randomized studies are needed to establish the clinical efficacy of recombinant cholera toxin B subunit.

Eosinophil granulocytes are activated during the remission phase of ulcerative colitis.

AIM: The aim of this study was to establish a method of investigating intestinal eosinophil and neutrophil granulocytes by flow cytometry, and to compare the distribution and activity of these cells in different stages of ulcerative colitis (UC). METHODS: Biopsy samples were taken from six locations of the entire colon and from the terminal ileum in 10 patients with active total UC, 10 patients with inactive total UC, eight patients with active distal UC, and 11 control subjects. Cell suspensions from biopsies and from peripheral blood were incubated with fluorophore conjugated monoclonal antibodies. The use of scatter plot-gating and specific antibodies was established in a flow cytometry assay. RESULTS: Eosinophils were more numerous and more active in patients with active UC than in controls. Interestingly, during inactive UC, the number of activated eosinophils was even larger. Eosinophil activity was high in the rectum of patients with distal colitis but was also slightly elevated in the proximal colon. Neutrophils were increased in number and activity during active but not inactive UC. In patients with distal colitis, activated neutrophils were only found in the sigmoid colon and rectum. CONCLUSION: With this method, we confirm that neutrophils participate in the inflammatory process during active UC, and that they express a resting phenotype during remission. The finding of activated eosinophils in inflamed intestine strengthens the view of these cells as proinflammatory and tissue damaging. Nevertheless, our new finding of high eosinophil activation during inactive UC suggests that eosinophils play a role in repair of injured epithelium.

Delayed gastric emptying in patients with diffuse versus limited systemic sclerosis, unrelated to gastrointestinal symptoms and myoelectric gastric activity.

OBJECTIVE: To study the gastric function in patients with diffuse and limited systemic sclerosis (SSc) in relation to the degree of upper gastrointestinal symptoms. METHODS: Scintigraphic gastric emptying and recording of the myoelectric signals of the stomach were examined in 15 patients with diffuse SSc (dSSc), 13 patients with limited SSc (lSSc) and 15 healthy controls. The frequency of upper gastrointestinal symptoms was determined using a questionnaire. RESULTS: Patients with dSSc had slower gastric emptying (scintigraphic gastric half-emptying time median (Md) 103 min, range 75-447 min) than control subjects (Md 70 min, range 38-94) and patients with lSSc (Md 76 min, range 43-460). Electrogastrographic recordings did not differ between dSSc, lSSc or controls. Symptoms tended to be more abundant in dSSc patients than in lSSc patients, however, patients with a high frequency of symptoms did not differ from patients with low frequency of symptoms in gastric function, as measured with scintigraphic gastric emptying or electrogastrography (EGG). Neither EGG nor a thorough review of upper gastrointestinal symptoms could predict delayed gastric emptying. CONCLUSION: The higher prevalence of delayed gastric emptying in patients with dSSc in this study indicates a more severe involvement of the gastrointestinal tract in dSSc than in lSSc, and stresses the importance of differentiating between the subtypes of SSc patients. Since EGG dysrythmia did not correlate with gastric emptying we concluded that factors other than defective myoelectric signals might contribute to a disturbed gastric function.

Gastric emptying in myotonic dystrophy.

BACKGROUND: Gastrointestinal symptoms are common and important for the quality of life in patients with myotonic dystrophy (MD). Gastric emptying was studied in patients with MD who suffered from symptoms suggesting slow gastric emptying and the effect of prokinetic treatment was evaluated. METHODS: Gastric emptying was studied in 10 patients with MD who were suffering from nausea, early satiety, bloating, regurgitation, vomiting, or abdominal pain using a (99)Tc-labelled test meal, and was compared with gastric emptying in a group of healthy controls. The patients were subsequently treated with erythromycin and their gastrointestinal symptoms were recorded and the gastric emptying test was repeated. RESULTS: Patients with MD had a significantly longer gastric lag phase (46.1 +/- 4.3 vs. 31.9 +/- 4.0 min, P = 0.03), a slower emptying phase (7.1 +/- 0.9 vs. 10.2 +/- 0.9 kJ min(-1), P = 0.02) and a longer half-emptying time, T50 (141.7 +/- 10.5 vs. 98.6 +/- 8.7 min, P = 0.01) than a matched control group. Erythromycin did not stimulate the gastric emptying rate. The effect on gastrointestinal symptoms was modest, except for a reduction of diarrhoea. CONCLUSIONS: Patients with MD suffering from nausea, vomiting and early satiety, displayed a slow gastric emptying. Treatment with erythromycin had only moderate effect on gastric emptying or gastric symptoms, but reduced diarrhoea in a majority of the patients.

Gastric myoelectrical activity and gut hormone secretion in myotonic dystrophy.

BACKGROUND: Myotonic dystrophy (MD) is a systemic disease affecting striated, cardiac and smooth muscles, as well as nerve structures and endocrine glands. Patients with MD may suffer from slow gastric emptying. OBJECTIVE: To study electrogastrograms (EGG) and postprandial gut hormone profiles in MD in order to evaluate whether disturbances in these regulatory mechanisms could explain, or contribute to, the delayed gastric emptying. SUBJECTS: Ten patients with MD complaining of symptoms consistent with slow gastric emptying, and ten healthy matched controls. METHODS: After an overnight fast, the patients and the control subjects were examined with standard EGG using surface electrodes before and during intake of a standard meal. Blood tests were drawn at regular time intervals for hormone analyses. RESULTS: The EGG in MD showed a reduced amount of normal three cycles per minute activity compared with controls (P < 0.04). The dominant frequency in MD was less stable than in controls (P < 0.03), and the power of the signal showed less increase after a meal. The postprandial increase in plasma motilin (P < 0.05) and glucagon-like peptide-1 (GLP-1) (P < 0.001) was significantly less pronounced in MD compared with controls, whereas the plasma concentrations of cholecystokinin (CCK), neurotensin (NT), peptide YY (PYY) and somatostatin (SOM) did not differ significantly. CONCLUSION: Disturbed electrophysiological control of the stomach and impaired secretion of gastrointestinal peptide hormones could contribute to slow gastric emptying in MD. Combined impairment of gastric pacing and gastrointestinal hormone responses was found in patients with the most prominent retardation of gastric emptying.

[Examination of gastric emptying with gamma camera. Clinically useful, uniform method now established]. / Undersökning av ventrikeltömning med gammakamera. Kliniskt användbar, enhetlig metod nu fastställd.

Although more than 30 years have passed since the introduction of scintigraphic testing of gastric emptying there has been no well-defined standard. Eight Swedish hospitals have established a nationally standardized method for scintigraphic testing of gastric emptying of solids. 160 healthy subjects participated. The meal consisted of a 99mTc-labeled omelet (1300 kJ) and 150 ml unlabeled soft drink (290 kJ). There were no differences in calculated variables between the centers. Premenopausal women showed slower emptying than postmenopausals and men of any age, making separate reference values for younger women necessary.

Intestinal endocrine cells in myotonic dystrophy: an immunocytochemical and computed image analytical study.

OBJECTIVES: To study intestinal endocrine cell types in patients suffering from myotonic dystrophy (MD) and diarrhoea. DESIGN: Comparative study between MD patients and matched controls. SETTING: Departments of Medicine, Central Hospital, Boden, and University Hospital, Umeå, Sweden. SUBJECTS: Ten patients with MD (four males and six females) and suffering from diarrhoea. Ten healthy volunteers served as controls for the duodenal study and 13 patients under investigation for rectal bleeding and with endoscopically normal mucosa were controls for the rectal study. MEASUREMENTS: The duodenal and rectal endocrine cell types were identified by immunohistochemical investigation and quantified by computed image analysis. RESULTS: The total endocrine cell area in the duodenum as demonstrated by chromogranin A-immunoreactivity was significantly increased in MD as compared with the controls (126 +/- 58 vs. 48 +/- 22 x 10(3) micron 2 mm-2 in crypts and 230 +/- 183 vs. 28 +/- 22 in villi, respectively, P < 0.01). The increase included all types of endocrine cells studied, namely those positive for serotonin, cholecystokinin (CCK)/gastrin, secretin, gastric inhibitory peptide (GIP) and somatostatin. In the rectum, the total endocrine cell area as determined by chromogranin A-immunoreactivity was also significantly increased, but there was no statistical difference between the controls and patients with respect to the area of serotonin-, peptide YY (PYY)-, pancreatic polypeptide (PP)- or somatostatin-immunoreactive cells. CONCLUSIONS: The increase in endocrine cell area indicates a disturbed endocrine regulation of the gastrointestinal tract that may contribute to the development of gastrointestinal symptoms encountered in MD patients.

Intestinal endocrine cells in myotonic dystrophy: an immunocytochemical and computed image analytical study.

OBJECTIVES: To study intestinal endocrine cell types in patients suffering from myotonic dystrophy (MD) and diarrhoea. DESIGN: Comparative study between MD patients and matched controls. SETTING: Departments of Medicine, Central Hospital, Boden, and University Hospital, Umeå, Sweden. SUBJECTS: Ten patients with MD (four males and six females) and suffering from diarrhoea. Ten healthy volunteers served as controls for the duodenal study and 13 patients under investigation for rectal bleeding and with endoscopically normal mucosa were controls for the rectal study. MEASUREMENTS: The duodenal and rectal endocrine cell types were identified by immunohistochemical investigation and quantified by computed image analysis. RESULTS: The total endocrine cell area in the duodenum as demonstrated by chromogranin A-immunoreactivity was significantly increased in MD as compared with the controls (126 +/- 58 vs. 48 +/- 22 x 10(3) microns 2 mm-2 in crypts and 230 +/- 183 vs. 28 +/- 22 in villi, respectively, P < 0.01). The increase included all types of endocrine cells studied, namely those positive for serotonin, cholecystokinin (CCK)/gastrin, secretin, gastric inhibitory peptide (GIP) and somatostatin. In the rectum, the total endocrine cell area as determined by chromogranin A-immunoreactivity was also significantly increased, but there was no statistical difference between the controls and patients with respect to the area of serotonin-, peptide YY (PYY)-, pancreatic polypeptide (PP)- or somatostatin-immunoreactive cells. CONCLUSIONS: The increase in endocrine cell area indicates a disturbed endocrine regulation of the gastrointestinal tract that may contribute to the development of gastrointestinal symptoms encountered in MD patients.

Mechanisms of diarrhoea in myotonic dystrophy.

BACKGROUND: Gastrointestinal (GI) symptoms are common in myotonic dystrophy (MD). Diarrhoea is one of the more disabling of these GI complaints. The mechanisms behind diarrhoea in MD have not previously been investigated systematically. OBJECTIVE: To elucidate the mechanisms behind diarrhoea in MD. METHODS: Twenty patients with MD and suffering from diarrhoea were investigated in order to detect malabsorption (blood tests and faecal fat excretion) and bile acid malabsorption ([75Se]selenahomocholic acid-taurine (SeHCAT) retention) and to study intestinal morphology (duodenal and rectal biopsies). RESULTS: Two patients had deficiency of folic acid and four showed reduced levels of pancreatic isoamylase, but none of them had steatorrhoea. Two out of eight patients had abnormal bile acid breath tests with normal SeHCAT, indicating small bowel bacterial overgrowth and 12 displayed reduced SeHCAT retention. Duodenal biopsies were normal in eight patients and five out of nine rectal biopsies displayed slight inflammation. CONCLUSIONS: A possible mechanism of diarrhoea in MD could be identified in most of the patients. Bile acid malabsorption seems to be a frequent cause and can be treated successfully.

Gastrointestinal symptoms in myotonic dystrophy.

BACKGROUND: Gastrointestinal complaints may be the initial symptom in myotonic dystrophy (MD). However, the frequency of gastrointestinal symptoms has never been prospectively evaluated. METHODS: Forty patients with MD were interviewed with regard to their GI symptoms with a standardized questionnaire. A group of healthy subjects matched for age and sex served as controls. RESULTS: The most prevalent symptoms were abdominal pain (55%), dysphagia (45%), emesis (35%), chronic or episodic diarrhoea (33%), coughing while eating (33%), and anal incontinence (30%). Twenty-five per cent of the patients considered their GI problems to be the most disabling consequence of the disease, and 28% had GI problems that started before the diagnosis of MD. CONCLUSIONS: GI symptoms are common in patients with MD, may be the initial symptoms, and are often considered to be the most disabling consequence of the disease.