Hallgrimur Gudjonsson

Subclinical intestinal inflammation: an inherited abnormality in Crohn’s disease relatives?

BACKGROUND & AIMS One approach to unraveling the genetics of complex inherited disease, such as Crohns disease, is to search for subclinical disease markers among unaffected family members. We assessed the possible presence, prevalence, and inheritance pattern of subclinical intestinal inflammation in apparently healthy relatives of patients with Crohns disease. METHODS A total of 49 patients with Crohns disease, 16 spouses, and 151 (58%) of 260 available first-degree relatives underwent a test for intestinal inflammation (fecal calprotectin concentration). The mode of inheritance was assessed from 36 index patients (by variance component analysis) when more than 50% of relatives were studied. RESULTS Fecal calprotectin concentrations in patients with Crohns disease (47 mg/L; confidence interval [CI], 27-95 mg/L) and relatives (11 mg/L; CI, 9-14 mg/L) differed significantly (P < 0.0001) from controls (4 mg/L; CI, 3-5 mg/L), whereas that of the spouses did not (4 mg/L; CI, 3-6 mg/L; P > 0.5). Fecal calprotectin concentration was increased in 49% of all relatives studied. The increased fecal calprotectin concentration among the relatives of the 36 index patients had an inheritance pattern that was most consistent with an additive inheritance pattern. CONCLUSIONS There is a high prevalence of subclinical intestinal inflammation in first-degree relatives of patients with Crohns disease that conforms best to an additive inheritance pattern. The genetic basis for this abnormality may represent a risk factor for Crohns disease.

Selective inhibition of COX-2 in humans is associated with less gastrointestinal injury: a comparison of nimesulide and naproxen

BACKGROUND Selective inhibitors of cyclooxygenase (COX)-2 may provoke less gastric damage and platelet inhibition than conventional non-steroidal anti-inflammatory drugs. AIMS We compared the biochemical and gastrointestinal effects of nimesulide, a potent and selective COX-2 inhibitor, with naproxen which exhibits no selectivity. SUBJECTS Thirty six healthy volunteers were randomised to nimesulide 100 mg or naproxen 500 mg twice daily for two weeks in a double blind, crossover study with a washout between treatments. METHODS Gastrointestinal side effects were assessed by endoscopy, and by estimation of small intestinal absorption-permeability and inflammation. Comparisons were made between variables at the end of each treatment phase. RESULTS Nimesulide caused significantly less gastric injury using the modified Lanza score (p<0.001) as well as reduced duodenum injury (p=0.039). Nimesulide had lower visual analogue scores (VAS) for haemorrhage and erosive lesions in the stomach (p<0.001) and for mucosal injection in the duodenum (p=0.039). Naproxen increased excretion of calprotectin, a marker of intestinal inflammation (5.5 (1.2) to 12.1 (2.1) mg/l) while nimesulide had no effect (treatment difference p=0.03). Naproxen abolished platelet aggregation to arachidonic acid and suppressed serum thromboxane B2 (TXB2) by 98%, indices of COX-1 activity. In contrast, nimesulide had no significant effect on platelet aggregation, although it reduced serum TXB2 by 29%. Production of prostaglandin E2 and prostacyclin by gastric biopsies, also COX-1 dependent, was inhibited by naproxen, but not by nimesulide. COX-2 activity, determined as endotoxin induced prostaglandin E2 formation in plasma, was markedly suppressed by both treatments. INTERPRETATION Nimesulide has preferential selectivity for COX-2 over COX-1 in vivo at full therapeutic doses and induces less gastrointestinal damage than that seen with naproxen in the short term.

In vivo studies of intestinal carnitine absorption in rats

We have studied small intestinal absorption of carnitine in vivo using a combination of segmental perfusion techniques and bolus intraluminal injection. We found evidence of a partially saturable absorption process (with Km values of 1035 and 1267 microM for jejunum and ileum calculated for the saturable component) that appeared to be separate from the imino acid transport system. Absorption was characterized by slow mucosal uptake, prolonged mucosal retention, and a very slow mucosal exit process with blood levels of [3H] carnitine still rising 8 h after intraluminal administration. We have also demonstrated the presence of carnitine acetyltransferase in intestinal mucosa and have shown that the intestine forms significant amounts of acetylcarnitine from exogenous carnitine.

Natural History of Functional Dyspepsia: A 10-Year Population-Based Study

Background: Functional dyspepsia (FD) is a common disorder, but information on its natural history is limited. Aim: To study the natural history of FD as assessed by 2 criteria over a 10-year period. Method: A population-based study conducted by mailing a questionnaire to the same age- and gender-stratified random sample of the Icelandic population aged 18–75 in 1996 and again in 2006. FD was estimated by the Functional Dyspepsia Score List and by dyspepsia subgroups categorized into 4 groups: (1) frequent upper pain, (2) meal-related, (3) nausea or vomiting, and (4) combinations of these groups. Results: FD was diagnosed in 13.9% of the subjects in the 1996 sample (11.3% male, 15.8% female) and 16.7% in 2006 (12.3% male, 20.2% female) with a significant difference between males and females in 2006. Dyspepsia subgroup criteria showed a higher prevalence than conventional FD criteria. The proportion of FD subjects in one of the dyspepsia subgroups was low. There was a significant relationship between FD and heartburn and irritable bowel syndrome. A high proportion of subjects who seek medical care have FD. Conclusion: FD was stable over the 10-year period, but there was turnover in symptoms and increased intensity and frequency of gastrointestinal pain. Dyspepsia subgroup criteria showed a higher prevalence than FD, which was more common in young subjects and females. FD poses a heavy burden on the health care system.

Natural history of functional gastrointestinal disorders: Comparison of two longitudinal population-based studies

BACKGROUND Functional gastrointestinal disorders are common but information on their natural history is limited. AIMS To document the natural history of functional gastrointestinal disorders in a population based study and to compare with the Olmsted County study. METHOD A questionnaire was mailed to the same age- and gender-stratified random sample of the Icelandic population aged 18-75 in 1996 and 2006. Results were compared to the Olmsted County study. RESULTS Prevalence of functional gastrointestinal disorder symptoms was stable between these periods in time: 16.9% and 17.2% for irritable bowel syndrome, and 4.8% and 6.1% for functional dyspepsia. Onset of each disorder was more often higher in the Olmsted County study than in Iceland. Disappearance rates were similar for both studies. Transition probabilities varied across the different subgroups and were different between studies. The same proportion had the same symptoms in the initial and final studies. More subjects had no symptoms in Iceland (52% vs. 40%) and different symptoms at follow up (38% vs. 23%). CONCLUSION Prevalence of functional gastrointestinal disorder symptoms was stable over time but the turnover in symptoms was high. A higher number of subjects had no symptoms in Iceland than in Olmsted County and there was a greater variation in subjects having different symptoms at follow up.

Irritable bowel syndrome: Physicians' awareness and patients' experience

AIM To study if and how physicians use the irritable bowel syndrome (IBS) diagnostic criteria and to assess treatment strategies in IBS patients. METHODS A questionnaire was sent to 191 physicians regarding IBS criteria, diagnostic methods and treatment. Furthermore, 94 patients who were diagnosed with IBS underwent telephone interview. RESULTS A total of 80/191 (41.9%) physicians responded to the survey. Overall, 13 patients were diagnosed monthly with IBS by specialists in gastroenterology (SGs) and 2.5 patients by general practitioners (GPs). All the SGs knew of the criteria to diagnose IBS, as did 46/70 (65.7%) GPs. Seventy-nine percent used the patients history, 38% used a physical examination, and 38% exclusion of other diseases to diagnose IBS. Only 18/80 (22.5%) physicians used specific IBS criteria. Of the patients interviewed, 59/94 (62.8%) knew they had experienced IBS. Two out of five patients knew IBS and had seen a physician because of IBS symptoms. Half of those received a diagnosis of IBS. A total of 13% were satisfied with treatment. IBS affected daily activities in 43% of cases. CONCLUSION Half of the patients with IBS who consulted a physician received a diagnosis. Awareness and knowledge of diagnostic criteria for IBS differ between SGs and GPs.

Natural History of Irritable Bowel Syndrome in Women and Dysmenorrhea: A 10-Year Follow-Up Study

Background. Studies have shown that women are more likely to have irritable bowel syndrome (IBS) and more women seek healthcare because of IBS than men. Aim. We wanted to examine the natural history of IBS and dysmenorrhea in women over a 10-year period and to assess the change in IBS after menopause. Method. A population-based postal study. A questionnaire was mailed to the same age- and gender-stratified random sample of the Icelandic population aged 18–75 in 1996 and again in 2006. Results. 77% premenopausal women had dysmenorrhea in the year 1996 and 74% in 2006. 42% of women with dysmenorrhea had IBS according to Manning criteria in the year 2006 and 49% in 1996. 26% of women with dysmenorrhea had IBS according to Rome III 2006 and 11% in the year 1996. In 2006 30% women had severe or very severe dysmenorrhea pain severity. More women (27%) reported severe abdominal pain after menopause than before menopause 11%. Women without dysmenorrhea were twice more likely to remain asymptomatic than the women with dysmenorrhea. Women with dysmenorrhea were more likely to have stable symptoms and were twice more likely to have increased symptoms. Conclusion. Women with IBS are more likely to experience dysmenorrhea than women without IBS which seems to be a part of the symptomatology in most women with IBS. IBS symptom severity seems to increase after menopause.

Natural history of heartburn: A 10-year population-based study

AIM To study the natural history and prevalence of heartburn at a 10-year interval, and to study the effect of heartburn on various symptoms and activities. METHODS A population-based postal study was carried out. Questionnaires were mailed to the same age- and gender-stratified random sample of the Icelandic population (aged 18-75 years) in 1996 and again in 2006. Subjects were classified with heartburn if they reported heartburn in the preceding year and/or week, based on the definition of heartburn. RESULTS Heartburn in the preceding year was reported in 42.8% (1996) and 44.2% (2006) of subjects, with a strong relationship between those who experienced heartburn in both years. Heartburn in the preceding week was diagnosed in 20.8%. There was a significant relationship between heartburn, dyspepsia and irritable bowel syndrome. Individuals with a body mass index (BMI) below or higher than normal weight were more likely to have heartburn. Heartburn caused by food or beverages was reported very often by 20.0% of subjects. CONCLUSION Heartburn is a common and chronic condition. Subjects with a BMI below or higher than normal weight are more likely to experience heartburn. Heartburn has a great impact on daily activities, sleep and quality of life.

Does Sucralfate Prevent Short-Term NSAID Induced Damage to the Gastroduodenal Mucosa?

The objective of the study was to assess whether sucralfate can prevent or diminish short-term nonsteroidal anti-inflammatory drug (NSAID)-induced damage in the stomach and duodenum. Sixteen healthy subjects were randomly treated for 7 days with sucralfate 2 g b.d. or placebo in a double-blind cross-over manner. Naproxen 500 mg b.d. was given on days 3-7. Gastrointestinal endoscopy was performed before and after each treatment period. Mucosal damage was measured by counting erosions, submucosal hemorrhages or ulcers on a fixed point scale of 0-4 for stomach and duodenum separately. The mean posttreatment injury score in the stomach was 2.13 +/- 1.51 and 2.0 +/- 0.97 for the placebo and sucralfate periods, respectively (p = 0.72). The possibility of type II error was 7%. In the duodenum, the injury score was 1.69 +/- 1.08 and 1.06 +/- 0.93 for the placebo and sucralfate periods, respectively (p = 0.08). The possibility of type II error was 37%. Sucralfate has no efficacy as a prophylactic agent against short-term NSAID-induced gastroduodenal injury.