Stability of the irritable bowel syndrome and subgroups as measured by three diagnostic criteria - a 10-year follow-up study.

BACKGROUND: The irritable bowel syndrome (IBS) is a common disorder, but information on its natural history is limited. AIM: To study the performance of four IBS criteria in detecting incidence and stability of categories over a 10-year period. METHOD: This study was a population-based postal study. Questionnaire was mailed to the same age- and gender-stratified random sample of the Icelandic population aged 18-75 years in 1996 and again in 2006. IBS was estimated by the Manning criteria, Rome II, Rome III, subgroups and self-report. RESULTS: Prevalence of IBS varied according to criteria: Manning showed the highest (32%) and Rome II the lowest (5%). Younger subjects and females were more likely to have IBS. Prevalence was stable over 10 years for all criteria except Rome III. There was a turnover in all IBS subgroups and a strong correlation among IBS, functional dyspepsia and heartburn. CONCLUSIONS: The prevalence of the IBS remained stable over a 10-year period with a turnover in symptoms. The study suggests that IBS is a cluster of symptoms that float in time between different IBS categories, functional dyspepsia and heartburn. The irritable bowel syndrome in Iceland is very common and indicates a chronic condition, which poses a heavy burden on the health care system.

Defective prevention of immune precipitation in autoimmune diseases is independent of C4A*Q0.

Increased prevalence of C4 null alleles is a common feature of autoimmune diseases. We have shown previously that complement-dependent prevention of immune precipitation (PIP) is defective in patients with systemic lupus erythematosus (SLE), and correlated this defect with C4A*Q0 and low levels of the C4A isotype. To further clarify the role of C4A in the aetiology of SLE, we now extend our studies to other diseases which have been associated with C4A*Q0. The frequency of C4A*Q0 was increased in Icelandic patients with coeliac disease (0.50; P < 0.001), Grave's disease (0.30; P = 0.002) and insulin-dependent diabetes mellitus (0.23; P = 0.04) and in British patients with dermatitis herpetiformis (0.42; P = 0.002) and this was reflected in low levels of C4A. In spite of this, PIP was normal in these patients, and in marked contrast to our previous observations on connective tissue diseases, PIP measurements in these patient groups correlated more strongly with levels of C4B (r = 0.51, P = 0.0000004) than C4A. Patients with increased levels of anti-C1q antibodies had significantly lower PIP than patients without such antibodies (P < 0.01) and a negative association of PIP with anti-C1q antibodies was also reflected in an increased prevalence (P = 0.006) and levels (P = 0.006) of anti-C1q antibodies in patients with subnormal PIP, as well as a negative correlation between PIP and anti-C1q antibodies (r = - 0.25, P = 0.02). These results show that the PIP defect cannot be explained by low levels of C4A alone and suggest that measurements of anti-C1q antibodies may be useful in future studies on the molecular cause of the PIP defect in autoimmune connective tissue disease.

Bilateral multifocal renal oncocytoma--a case report and literature review.

A case of bilateral multifocal renal oncocytoma is reported. The incidence, diagnosis and management of such tumors is discussed.

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 B(2) (TXB(2)) by 98%, indices of COX-1 activity. In contrast, nimesulide had no significant effect on platelet aggregation, although it reduced serum TXB(2) by 29%. Production of prostaglandin E(2) 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 E(2) 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.

Omeprazole and ranitidine in the prevention of relapse in patients with duodenal ulcer disease.

BACKGROUND: Although the eradication of Helicobacter pylori is of primary importance when initiating treatment, it is also important to have a strategy for patients who are H pylori-negative, fail to demonstrate eradication or have a tendency to become re-infected or relapse. PATIENTS AND METHODS: In a double-blind, parallel-group clinical trial of 928 patients (from 70 centres in 16 countries) with duodenal ulcers who after a short term study had relief of symptoms and healed ulcers proved endoscopically, 308 were randomly assigned to receive omeprazole 10 mg in the morning, 308 to receive omeprazole 20 mg in the morning and 312 to receive ranitidine 150 mg at bedtime for up to 12 months. Symptoms were assessed every three months and endoscopy repeated at three, six and 12 months, or more often if indicated by recurrence of symptoms. The safety screening included basal serum gastrin concentrations and gastric mucosal histopathology. RESULTS: The remission rates up to 12 months were 87% for the omeprazole 20 mg group, 71% for the omeprazole 10 mg group and 63% for the ranitidine group. Omeprazole 20 mg differed significantly from both omeprazole 10 mg (P=0.0001, 95% CI 9 to 23) and ranitidine (P=0.0001, 95% CI 17 to 31). There was no statistically significant difference between omeprazole 10 mg and ranitidine over the 12-month period, but the 95% confidence interval allowed differences between 0% and 16% in favour of omeprazole at 12 months. A Cox regression analysis revealed that longer treatment courses to heal, smoking, a long ulcer history and young age negatively contributed to the odds of staying in remission. The treatments were well tolerated. There was a slight increase in basal serum gastrin concentrations, reflecting the different degrees of acid inhibition induced by the three treatments. No dysplastic or neoplastic lesions were found in any biopsies. CONCLUSIONS: More duodenal ulcer patients are maintained in remission with omeprazole 20 mg daily than with omeprazole 10 mg daily or with ranitidine 150 mg at bedtime.

[Herpes simplex esophagitis in immunocompetent individuals.].

OBJECTIVE: Infections by herpes simplex viruses (HSV) are common but esophageal involvement is relatively rare. It is most frequently diagnosed in immunocompromized patients. We describe four healthy, young men with HSV esophagitis and review the literature on the subject. MATERIAL AND METHODS: The diagnosis of HSV esophagitis was considered likely if three out of four of our criteria were met but definite if all four were fulfilled. IgM and IgG against HSV was measured with two different ELISAs. Viral culture was done in Vero and A-549 cells. Virus typing was done with ELISA. Histopathological exam was performed. A MEDLINE search of HSV esophagitis among otherwise healthy individuals was performed and the literature reviewed. RESULTS: Four young, healthy men were diagnosed with HSV esophagitis in 1997. Diagnosis was likely in two cases and definite in two. One patient was initially suspected of heart disease and another of gallbladder disease. All four patients were proven to have primary infection, were hospitalized, given intravenous hydration and treated with acyclovir. A MEDLINE search revealed 12 other cases of HSV esopha notgitis in otherwise healthy individuals. Including all 16 cases, the age ranged from 18 to 50 years (mean age 26 years). There were two women and 14 men. The most frequent symptom was odynophagia (69%). Eight patients (50%) had fever but only six (37.5%)had lesions in skin and/or mucosa on examination. Esophageal ulcers or inflammation were detected in all patients. The changes were in the distal esophagus (13/16), in the middle (2/16) or the entire organ (1/16). HSV-1 was cultured from 10 patients. Viral inclusions were seen in esophageal samples from eight patients. HSV antibodies were measured in 10 patients, six of which were proven to have primary infection. CONCLUSIONS: HSV esophagitis is rare in otherwise healthy individuals but probably underdiagnosed. Most cases are young men. Clues to the diagnosis such as visible lesions in skin or mucosae are frequently not present. Vigilance and endoscopy with biopsies and culture is needed for an accurate diagnosis.

High Helicobacter pylori eradication rate with a 1-week regimen containing ranitidine bismuth citrate.

BACKGROUND: High Helicobacter pylori eradication rates have consistently been reported with 2-week dual therapy regimens of ranitidine bismuth citrate plus clarithromycin. Ranitidine bismuth citrate with two antibiotics may provide an alternative 1-week eradication regimen. METHODS: This double-blind, randomized, parallel group, international, multicentre study compared ranitidine bismuth citrate 400 mg b.d. and clarithromycin 500 mg b.d. for 2 weeks (RC) with ranitidine bismuth citrate 400 mg b.d., clarithromycin 500 mg b.d. and metronidazole 400 mg b.d. for 1 week (RCM) for eradication of H. pylori in 350 patients with dyspepsia. RESULTS: Treatment with RC and RCM eradicated H. pylori (established by the combination of two negative results from two discrete 13C-UBTs at nominal weeks 4 and 12) from 89% (95% CI: 84-94) and 92% (95% CI: 88-97) of the observed population, and from 78% (95% CI: 72-84) and 80% (95% CI: 75-86) of the intention-to-treat population. When established only by one negative 13C-UBT result at least 28 days after the end of treatment, the respective intention-to-treat rates were 85% (95% CI: 79-90) and 88% (95% CI: 83-93). Both regimens were well-tolerated, only 6% of patients given RC and 4% given RCM discontinued treatment. Median plasma bismuth concentrations at the end of the second week of study were low, at 3.5 and 0.4 ng/ mL, respectively. CONCLUSIONS: Ranitidine bismuth citrate triple therapy for 1 week (RCM) and dual therapy for 2 weeks (RC) were equally effective for the eradication of H. pylori infection.

[Comparison of the efficacy of Losec/Lómex and Zantac/Famex by continuous 24 hour gastric pH-metry.].

OBJECTIVE: The study proposes to investigate the pharmacological efficacy of four commonly used acid inhibitory drugs. The effect on 24 hour gastric pH of seven days treatment was assessed for two omeprazole preparations, Losec(R) 20 mg (Hassle) and Lómex(R) 20 mg, (Omega Farma) and two H2 blockers, famotidine 40 mg (Famex(R), Omega Farma) and ranitidine 300 mg (Zantac(R), Glaxo). MATERIAL AND METHODS: Sixteen healthy volunteers participated in each experiment comparing blindly Losec(R) / Lómex(R) and Famex(R) / Zantac(R). The stomach was intubated with monocrystant antimony catheter and the pH sensor was placed 10 cm below the cardia. A 24 hour control pH-metry was performed followed by a 24 hour pH-metry on the seventh day of treatment with each drug. RESULTS: All four drugs gave significant acid inhibition compared to control. Zantac treatment resulted in a pH over 3 for 8.8 hours and correspondingly Famex(R) treatment for 11.2 hours, Losec(R) treatment for 17.5 hours and Lómex(R) for 18.3 hours. Famex(R) gave significantly greater inhibition than Zantac(R) but the difference between Lómex(R) and Losec(R) was not significant. CONCLUSION: The study shows the efficacy of com notmonly used acid lowering drugs on the Icelandic market. The relative efficacy is indicated by the fact that Zantac(R) increased the median time for pH over 3 by 2.6 hours, Famex(R) by 5.0 hours, Losec(R) by 11.3 hours and Lómex(R) by 12.1 hours.

[Endoscopic retrograde cholangio- pancreatography. An overview of procedures at the Natinal University Hospital in Reykjavik 1983-1992.].

INTRODUCTION: In this retrospective study we analysed all ERCP procedures performed at the National University Hospital in Reykjavik, Iceland, for the period 1983-1992. MATERIAL: A total of 644 procedures were performed on 477 patients. RESULTS: The main indication for a diagnostic ERCP was suspected choledocholithiasis in 58.8% of cases. Cannulation of the papilla of Vater was successfully achived in 94% of patients and in 82% the desired duct was visualised. Juxtapapillary diverticula were found in 14.5% of patients. The success at cannulation was significally less in that group. Choledocholithiasis was found in 19.4% more often in the patients with diverticula, 29.5 vs. 18.8%. The number of therapeutic interventions was 158 performed on 84 patients (24.5% of all ERCP). The most common procedure was sphincterotomy, performed in 84% of cases. Stone extraction was successfully achived in 58% of all attempts. The overall complications rate was 7%, most frequently acute pancreatitis (4.7%) followed by cholangitis (1.9%) and bleeding (0.3%). The complications were mild in the majority of cases but serious ones did occur and were fatal in three (0.5%) patients related to severe pancreatitis. CONCLUSION: The results of this retrospective study in Iceland are comparable to what others have reported previously.

[Drug administration and expenses for irritable bowel syndrome in Iceland.].

OBJECTIVE: To study the use and value of drugs used for irritable bowel syndrome (IBS) in Iceland and compare with other Nordic countries. METHODS: A retrospective study was performed. Information on use and value of IBS-drugs was obtained from the Ministry of Health. Five years period 1989-1993, was investigated. Mebeverine, butylscopolamine and clidine, all the drugs in the A03 group were studied. Furthermore it was estimated that in 50% of cases ispaghula fibers were used for IBS. The use was measured in daily defined doses (DDD) per 1000 inhabitants and the value was calculated according to wholesaleprice from pharmacies on the 1st of November 1993. Information from the Nordic statistics on medicine was utilized to compare Iceland with other Nordic countries for the period 1990-1992. RESULTS: In Iceland the administration and expenses of IBS-medications decreased significantly during the investigated period. The use decreased from 7.96 DDD to 4.57 DDD, from the beginning to the end of the period. The total drug cost decreased of 45%, from 50 to 28 millions ISK. The use of A03-drugs is much more common in Iceland, than in Denmark, Norway and Sweden. IBS-drugs expenses are by far the highest in Iceland, twice to three times higher than in other Nordic countries. CONCLUSION: The administration and expenses of IBS-drugs in Iceland is substantial, but it is decreasing. IBS-drug therapy in Iceland is more common and expensive than in other Nordic countries.

[A nationwide epidemiological study on celiac disease - the Icelandic picture.].

UNLABELLED: We undertook an epidemiological study of celiac disease (CD) in Iceland for the period 1962-1991. Twenty-eight patients, two of whom were children met the criteria for inclusion. The median age at diagnosis was 34 years, and the female:male ratio was 3:1. The majority of patients, 24 (86%), were diagnosed during the last of three decades studied. The annual incidence rate during the most recent 10-year period was 1:100,000. The point prevalence at the end of 1991 was 1:9,600. The incidence for children was 0.016:1000. The patients' geographical distribution within Iceland was uneven, with an unexpected preponderance of patients living in the country's north-eastern region. These apparent differences in topographical distribution may represent thoroughness in identification of patients rather than actual regional differences in frequency of the disease. The clinical features of CD are similar to those previously reported. Retrospectively analysed, the mean diagnostic delay was 16 years. The utility rate of small bowel biopsies in patients suspected of CD was low, 0.028 in adults and 0.013 in children. CONCLUSION: Celiac disease is far less prevalent in Iceland, especially among children, than elsewhere in north-western Europe. The incidence of CD has, however, risen markedly in recent years.

[A giant epiphrenic esophageal diverticulum in a patient with history of Zenker's diverticulum.].

A sixty-three years old man, post Zenker's diverticulectomy, presented with a giant epiphrenic esophageal diverticulum. The diverticulum, which was symptomatic and progressively enlarging, was successfully removed by simple excision.

[Irritable bowel syndrome. Epidemiological study on young people in Iceland.].

An epidemiological study on Irritable Bowel Syndrome (IBS) was done on 411 otherwise healthy young subjects in Iceland. A questionnaire was used, based on socalled Manning's criteria for IBS (Br Med J1978; 2: 633). IBS was diagnosed if two or more of the six Manning's criteria were positive. It was asked if these criteria (symptoms) were associated with stress or required medical treatment. Furthermore the questionnaire addressed 13 other symptoms related to the gastrointestinal tract (GI). For analysis we could use answers of 400 subjects, 63.2% females, 36.8% males, most of them (93.5%) 19-29 years old. 37.9% met the criteria of IBS, and the diagnosis was significantly more often present among women (46.6%) than men (22.5%). Usually the IBS symptoms are related to stress, but few received medical treatment. All the 13 other GI symptoms are more frequent in IBS subjects than the others and there was a significant association of IBS with nausea, upper abdominal pain, bloating, constipation, painless diarrhea and flatulence. In summary, the results of this study suggest that: (i) IBS is very common among young adults in Iceland, (ii) prevalence in Iceland is higher than reported elsewhere, (hi) the female:male ratio is 2:1, (iv) stress is a precipitating factor in IBS, (v) it is suggestive that few patients with IBS seek medical attention, (vi) IBS patient have, beside classical IBS symptoms, more frequently other digestive symptoms, which are suggestive of both upper and lower GI functional disorders.

[The effect of coffee and tea upon lower esophageal sphincteric function.].

The effects of coffee and tea upon lower esophageal sphincteric (LES) function were examined in a blinded crossover study of 12 healthy subjects. Lower esophageal sphincter pressure (LESP) and lower esophageal (LE) pH were measured simultaneously by a sleeve sensor and a pH probe for 20 minutes before and 90 minutes after intragastric instillation of four test solutions, which contained either regular coffee (C), decaffeinated coffee (D), tea (T) or water (W). C and T solutions had the same caffeine content, 160 mg. As compared with control (W), LESP was significantly lower after C and T, but not after D. The data for LE pH paralleled those for LESP. Thus, the greatest number of reflux episodes occurred after T and C. Difference from control (W) was statistically significant for T but not for C. We conclude that both regular coffee and tea have adverse effects upon LES function, whereas decaffeinated coffee does not. This study provides a rational basis for limiting intake of both caffeinated coffee and tea in patients with clinically important gastroesophageal reflux.

[Helicobacter pylori infection: the efficacy of a short course of azithromycin and fleroxacin treatment.].

The aim of this open pilot study was to assess the efficacy of a short course of fleroxacin and azithromycin in the treatment of Helicobacter pylori infection. Seventeen patients were included. All had H. pylori infection confirmed by urease test and culture. Eight patients had non-ulcer dyspepsia, 8 had duodenal ulcer and 1 had gastric ulcer. The patients were given omeprazole 40 mg on days 1-14, fleroxacin 400 mg on days 7-14 and azithromycin 500 mg on days 7 and 8. Side effects were assessed on a scale 0-4. The patients were gastroscoped 3 months after the treatment finished and urease test and H. pylori culture repeated. If both were negative eradication was regarded as successful. Six patients (35%) were H. pylori negative. However, only 1 (13%) of the patients with non-ulcer dyspepsia became H. pylori negative, whereas 5 (56%) with peptic ulcer did (P=0,131). The mean side effect score for patients with non-ulcer dyspepsia was 12.3, but 2.3 for patients with peptic ulcer (p<0,01). It is concluded that a short course with fleroxacin and azithromycin is inadequate for treatment of H. pylori infection.

[Helicobacter pylori infection: The efficacy of bismuth-tetracyclin-metronidazole triple therapy in patients with duodenal ulcer.].

The aim of the study was to assess the efficacy of two bismuth-tetracyclin-metronidazole "triple therapy" regimes for Helicobacter pylori and their effect of eradication of the bacteria on duodenal ulcer disease. Eighty-two patients (52 males and 30 females, mean age 49 years) with a history of recurrent duodenal ulcer and H. pylori postitive gastritis were included in the study. Treatment I, 35 patients, received colloid bismuth subcitrate (De-Nol(R)) 120 mg q.i.d, tetracyclin 500 mg q.i.d. and metronidazole 400 mg t.i.d. for 14 days. Most patients received omeprazole or H2 blocker during the treatment. Treatment II, 47 patients, received omeprazole 20 mg o.d. on days 1-14 and colloid bismuth subcitrate 120 mg q.i.d., tetracyclin 250 mg q.i.d. and metronidazole 250 mg q.i.d. on days 4-14. Eradication was regarded successful if gastric biopsy was H. pylori negative by urease test three months or more after treatment. All patients were able to complete the treatment. Eradication of H. pylori was successful in 34 (97%) in group I and in 43 (92%) in group II. The mean endoscopic follow-up period was 9.4 months in group I and 16.0 in group II. Follow-up with regard to subjective symptoms was on average 20 months long. Five patients in group I and eight in group II had a mild symptom recurrence without reinfection. Two (2.5%) patients (one in each group) had a recurrent ulcer. Adverse effects were common in both groups and four patients, all in group I, had severe symptoms. It was estimated that the successful H. pylori eradication and excellent symptom response in most of the patients had saved seven million Icelandic krónur in drug expenses in the whole group.

The association between coeliac disease, dermatitis herpetiformis and certain HLA-antigens in Icelanders.

Twenty-eight cases of coeliac disease (CD) and seven of dermatitis herpetiformis (DH) have been verified in Iceland. Standard serological techniques were used for HLA typing. Twenty-five individuals with CD were typed, 21 (84%) of whom carried DR3,DQ2. Twelve of these 25 (48%) had DR3,DR7, DQ2, which makes them possibly homozygous for DQ2, and suggests that homozygosity of DQ2 increases the risk for CD. The four DH patients that were typed all had HLA-B8,DR3,DQ2. It is concluded that CD and DH are associated with DR3, DQZ in Icelanders.

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.

Efficacy of sucralfate in treatment of non-ulcer dyspepsia. A double-blind placebo-controlled study.

The object of this study was to assess the efficacy of sucralfate in the treatment of non-ulcer dyspepsia (NUD). The diagnosis of NUD was made by exclusion. All patients underwent an upper gastrointestinal endoscopy and abdominal ultrasound, and blood tests were done as clinically indicated. Patients with a history of peptic ulcer disease were not included. Symptomatic assessment was made at the beginning and at the end of the study. The patients registered their most prominent dyspeptic symptoms and whether they improved, were unchanged, or worsened. The study was double-blind. Placebo or 1 g sucralfate four times daily was given for 3 weeks. Over a 2-year period 104 patients were included in the study; 56 received sucralfate and 48 placebo. Nine patients were excluded because of poor compliance or side effects, six from the sucralfate group and three from the placebo group. The sucralfate and placebo groups were comparable with regard to symptom and clinical variables. Global assessment of symptoms showed that in the sucralfate group 34 improved (68%), 11 were unchanged, and 5 were worse. In the placebo group 31 improved (69%), 11 were unchanged, and 3 were worse. There was no statistically significant difference between the groups. The 3-week course of sucralfate in patients with NUD did not show symptomatic improvement over placebo.