Treatment of irritable bowel syndrome with osteopathy: results of a randomized controlled pilot study

BACKGROUND AND AIM: Effective treatment for irritable bowel syndrome (IBS) is not yet available. Osteopathy is a manual treatment which relies on mobilizing and manipulating procedures in order to relieve complaints. In the present study, a randomized controlled trial was carried out to evaluate the effects of osteopathic treatment for IBS. METHODS: Eligible IBS patients were randomized between osteopathy and standard care. Follow-up was 6 months and validated means of follow-up were used. After 1, 3 and 6 months an overall assessment of symptoms was noted and a symptom score was obtained on a 5-point Likert scale. Quality of life (QOL) was scored with the standardized IBSQOL 2000 questionnaire and the Functional Bowel Disorder Severity Index was used. RESULTS: Twenty patients were randomized into the osteopathy group (OG) and 19 patients were included in the standard care group (SCG). Sixty-eight percent of patients in the OG noted definite overall improvement in symptoms and 27% showed slight improvement. One patient (5%) was free of symptoms at the end of the study. In the SCG, 18% noted definite improvement, 59% showed slight improvement, and in 17% worsening of symptoms was present. The difference in change in overall symptomatic improvement was statistically significant in favor of the osteopathic treatment (P < 0.006). Mean Functional Bowel Disorder Severity Index (FBDSI) score in the OG decreased from 174 to 74 at 6 months (P < 0.0001). Also, a significant decrease was noted in the SCG from 171 to 119 (P < 0.0001). However, the decrease in the OG was significantly higher compared with the standard treatment (P = 0.02). Mean symptom score in the OG decreased from 9.1 to 6.8 but this did not reach statistical significance. In the SCG, no change in symptom score occurred (8.7 vs 10). At 6 months, the score in the OG was significantly lower (6.8 vs 10; P = 0.02). The QOL score increased in the OG at 111 versus 129 (P < 0.009). In the SCG an increase was also noted, but this was not statistically significant (109 vs 121). CONCLUSION: Osteopathic therapy is a promising alternative in the treatment of patients with IBS. Patients treated with osteopathy overall did better, with respect to symptom score and QOL

Whipple's disease: a difficult diagnosis?

Whipple's disease: a difficult diagnosis? Peters FP, Elbrecht EA, Wouters RS, Engels LG, Stockbrugger RW. Department of Gastroenterology, University Hospital Maastricht, Netherlands. We present 3 patients with Whipple's disease all characterized by a longstanding prodromal period with progressive weight loss, diarrhoea, lymphadenitis and arthralgia or arthritis. Sarcoid-like Whipple's disease was diagnosed in one patient. He was treated with antibiotics. Initially his condition improved; however, a cerebral relapse developed which was treated successfully by ceftriaxone and cefixime. Extraintestinal Whipple's disease (lymph node localisation) was diagnosed in another patient treated successfully with antibiotics. A third case of Whipple's disease was unexpectedly diagnosed by laparotomy and partial small bowel resection. He was not treated till 2 years later with tetracycline. After 1 year of treatment his condition had improved. Publication Types: Case Reports Review Review, Tutoria

Intragastric volatile N-nitrosamines, nitrite, pH, and Helicobacter pylori during long-term treatment with omeprazole.

Gastroenterology 2001 Sep;121(3):517-25 Related Articles, Books, LinkOut Intragastric volatile N-nitrosamines, nitrite, pH, and Helicobacter pylori during long-term treatment with omeprazole. Vermeer IT, Engels LG, Pachen DM, Dallinga JW, Kleinjans JC, van Maanen JM. Department of Health Risk Analysis and Toxicology, Maastricht University, Maastricht, The Netherlands. [email protected] BACKGROUND & AIMS: This study evaluated the effect of long-term gastric acid suppressive therapy with omeprazole on intragastric levels of carcinogenic N-nitrosamines and related parameters. METHODS: Forty-five patients on long-term omeprazole medication (mean, 35 months) and 13 healthy subjects without medication participated. Volatile N-nitrosamines were determined in gastric juice and urine. Intragastric pH, nitrite, nitrate, and H. pylori status were determined. DNA isolated from gastric biopsy specimens was analyzed for precarcinogenic alkyl-DNA adducts. RESULTS: The intragastric pH in patients was significantly higher compared with controls (P = 0.0001). Gastric nitrite levels in patients were nonsignificantly higher. There was no difference in total levels of intragastric volatile N-nitrosamines between patients and controls, however, urinary N-nitrosodimethylamine excretion was higher in patients (P = 0.001). On omeprazole, Helicobacter pylori-positive vs. -negative patients had a nonsignificantly higher intragastric nitrite level and higher urinary N-nitrosodimethylamine excretion. No alkyl-DNA adducts could be detected in gastric epithelium. CONCLUSIONS: Increased intragastric pH caused by long-term treatment with omeprazole does not result in increased intragastric levels of nitrite and volatile N-nitrosamines. The significantly higher urinary N-nitrosamine excretion implies the risk of increased endogenous formation of N-nitrosamines during long-term omeprazole treatment. This risk may be higher in H. pylori-positive patients

Modern life' in the epidemiology of inflammatory bowel disease: a case-control study with special emphasis on nutritional factors.

Department of Gastroenterology, University Hospital Maastricht, The Netherlands. [email protected] OBJECTIVE: The rising incidence of inflammatory bowel disease (IBD) since the Second World War coincides with profound changes of the dietary pattern. The aim of the study was to investigate the possible pathogenic role of some characteristic 'modern life' dietary factors in IBD. DESIGN: Case-control, studying risk factors in recently diagnosed cases, 290 with Crohn's disease and 398 with ulcerative colitis, compared with 616 population controls. Smoking, age, gender and education were taken into account by using logistic regression analysis. SETTING: Hospital cases and population controls. INTERVENTIONS: Questionnaires. MAIN OUTCOME MEASURES: Logistic regression-derived odds ratios. RESULTS: A positive association with cola drinks [OR: 2.2 (95% CI 1.5-3.1)], chewing gum [OR: 1.5 (95% CI: 1.1-2.1)] and chocolate consumption [OR: 2.5 (95% CI: 1.8-3.5)] and a negative association with citrus fruit consumption [OR: 0.5 (95% CI 0.3-0.7)] and the development of Crohn's disease were found. Consumption of cola drinks [OR: 1.6 (95% CI 1.1-2.3)] and chocolate consumption [OR: 2.5 (95% CI 1.8-3.5)] were positively associated with developing ulcerative colitis. There was a negative association between the intake of citrus fruits [OR: 0.5 (95% CI 0.4-0.8)] and 'having a stuffed pet' for a period longer than 5 years [OR: 0.6 (95% CI 0.4-0.9)] and developing the disorder. No association with the frequency of tooth brushing and developing IBD was found. CONCLUSION: All the nutritional items mentioned may be true risk factors or they just might be the expression of a modern life-style also involving other risk factors for the development of IBD which at the present are still unknown

Toxicity of 6-thioguanine: no hepatotoxicity in a series of IBD patients treated with long-term, low dose 6-thioguanine Some evidence for dose or metabolite level dependent effects?

BACKGROUND: 6-Thioguanine is used in inflammatory bowel disease since 2001, with promising short-term results. In 2003, liver histology of some 6-thioguanine treated patients showed nodular regenerative hyperplasia. Recently, magnetic resonance imaging revealed nodular regenerative hyperplasia in patients with normal histology. AIMS: Investigating the presence of nodular regenerative hyperplasia in long-term 6-thioguanine treated patients. PATIENTS AND METHODS: Inflammatory bowel disease patients, using 6-thioguanine minimally 24 months, were asked to undergo liver biopsy and magnetic resonance imaging. RESULTS: Fourteen patients used 6-thioguanine minimally 24 months, 13 participated. Mean 6-thioguanine therapy duration, daily dose and 6-thioguanine nucleotide levels were: 36 months, 18.8mg (0.28mg/kg) and 705pmol/8x10(8) erythrocytes, respectively. Liver histology and magnetic resonance imaging showed no nodular regenerative hyperplasia. DISCUSSION: Liver biopsy and magnetic resonance imaging showed no nodular regenerative hyperplasia in these long-term 6-thioguanine treated inflammatory bowel disease patients. 6-Thioguanine dose and metabolite levels were lower compared with previous nodular regenerative hyperplasia reports, suggesting dose or metabolite level-dependent effects. Otherwise, nodular regenerative hyperplasia is related with inflammatory bowel disease itself and immunosuppressives, including azathioprine and 6-mercaptopurine. CONCLUSION: 6-Thioguanine is debated due to nodular regenerative hyperplasia. We found no nodular regenerative hyperplasia in inflammatory bowel disease patients with long-term, low dosed 6-thioguanine, suggesting metabolite level-dependent effects. Therefore, 6-thioguanine still seems useful, but in selected patients, intolerant for other immunosuppressives, low dosed and under close surveillance of metabolite levels and hepatotoxity. AD - Department of Gastroenterology and Hepatology, University Hospital Maastricht, Maastricht, The Netherlands

Neutrophil-mediated formation of carcinogenic N-nitroso compounds in an in vitro model for intestinal inflammation

In order to study neutrophil-mediated formation of carcinogenic N-nitroso compounds as a mechanism of inflammation-related colon carcinogenesis, we designed an in vitro model for intestinal inflammation, consisting of a coincubation system with human colon cells (Caco-2 cells) and activated human neutrophils (PMN), as important immunoreactive cells. We investigated whether nitrosamines and nitrosamides could be formed upon addition of dimethylamine, morpholine and methylurea to the coincubations as nitrosatable precursors, which are known to produce carcinogenic N-nitroso compounds. Incubations of pure nitric oxide with dimethylamine and morpholine showed that NO-mediated formation of nitrosodimethylamine and nitrosomorpholine is possible under the incubation conditions. During the coincubations of activated PMN and Caco-2 cells, 0.34nmol nitrite/10(6) PMN was produced. Dose-dependent formation of NMOR was observed in this PMN/Caco-2 system; addition of 5mM morpholine resulted in a significantly increased NMOR formation of 4.2nM. However, no detectable NDMA and methylnitrosourea were formed in this coincubation system. These results suggest that activated human neutrophils are able to synthesize carcinogenic N-nitrosamines, e.g. NMOR, which implies a risk of colon carcinogenesis during chronic inflammation. However, the observed relatively low level of nitrosation suggests that also other risk factors are contributing to the association between chronic inflammation and colon cancer risk

Altered vegetable intake affects pivotal carcinogenesis pathways in colon mucosa from adenoma patients and controls

The evidence from epidemiological and experimental studies that vegetables reduce the risk of colorectal cancer is convincing. However, the involved genes and genetic pathways are not clear. The aim of this study was to identify genes that are modulated in vivo in colorectal mucosa by vegetables, and to investigate whether colon adenoma patients respond differently compared with healthy controls. Twenty female adenoma patients and eight healthy controls were randomly split into two groups of ten and four persons, respectively, receiving either a 50% decreased (=75 g/day) or doubled (=300 g/day) intake of vegetables for 2 weeks. In order to assess the effects on gene expression at the target level, colorectal biopsies were collected before and after the intervention. Total RNA was isolated from the biopsies to measure gene expression of 597 genes relevant for responses to xenobiotics by microarray technology, followed by confidence analyses to identify differentially expressed genes. Mainly genes related to cell cycle control and genes for oxidoreductase activities were over-represented in the list of modulated genes. Twenty genes were modulated, which are known to be related to (colon)carcinogenesis. Seven genes were similarly modulated in patients and controls, for example fos proto-oncogene and ornithine decarboxylase. Thirteen genes were modulated differently in patients compared with controls, including cyclooxygenase-2 and human mdm2-A in patients and cytochrome P45027B1, -2C19, -2D6, -2C9 and -3A4 in controls. Almost all the effects on modulating the expression of genes by altering vegetable intake can be mechanistically linked to cellular processes that explain either prevention of colorectal cancer risk by high vegetable intake or increased colorectal cancer risk by low vegetable intake. Furthermore, it seems that vegetables in patients affect genes involved in the late stage of colorectal cancer, whereas in controls genes involved in the initiation phase are modulated

Proton pump inhibitor use is associated with an increased risk for microscopic colitis: a case-control study

Aliment Pharmacol Ther 2010; 32: 1124-1128 SUMMARY: Background Microscopic colitis causes chronic watery diarrhoea. Recent studies have suggested an aetiological role for various medications, including proton pump inhibitors, in the pathogenesis of microscopic colitis. Aim To determine whether an association exists between microscopic colitis and proton pump inhibitor use in patients with documented microscopic colitis vs. age- and gender-matched controls. Methods In this retrospective case-control study, cases of microscopic colitis from a secondary and tertiary referral medical centre diagnosed in the last 5 years were reviewed. Demographic characteristics, clinical, histological and endoscopic records, as well as exposure to PPIs and NSAIDs were assessed. Controls from the population were matched to cases by gender and by age. Results During the investigated period, 136 cases were identified in both hospitals. Of these, 95 cases of microscopic colitis were retrieved for detailed analysis. Exposure to proton pump inhibitors at the time of the histological diagnosis was significantly higher in patients with collagenous colitis than in controls [38% vs. 13%, P < 0.001; adjusted OR of 4.5 (95% CI 2.0-9.5)]. Conclusions This observation confirms the presumed association between microscopic colitis and PPI use, and it supports the possible aetiological role of PPI exposure in the development of microscopic colitis

Proliferating cell nuclear antigen (PCNA): a new marker to study human colonic cell proliferation

Immunohistochemistry of the S phase related proliferating cell nuclear antigen (PCNA) was studied as an alternative to ex-vivo bromodeoxyuridine (BrdU) immunohistochemistry for assessment of human colonic cell proliferation. From 16 subjects without colonic disease biopsy specimens were collected from five different sites along the colorectum and processed for BrdU and PCNA immunohistochemistry. The mean proliferation index of PCNA was significantly higher at 133% of the value obtained with BrdU. There was, however, a good correlation between the results from both techniques (r = 0.6275; p < 0.05). Decrease in proliferation index along the colorectum was seen with both staining methods but was clearer with PCNA immunohistochemistry (caecum/ascending colon v rectum: 12.0 v 7.2; p < 0.004). The total number of crypt cells also decreased from proximal to distal (134 to 128; p < 0.06) but at no site correlated significantly with the proliferation index. It is concluded that in clinical cell kinetic studies staining for PCNA may serve as an attractive alternative to the BrdU incorporation assay