Octatropine methyl bromide and diazepam combination (Valpinax) in patients with irritable bowel syndrome: a multicentre, randomized, placebo-controlled trial.

OBJECTIVE: To investigate the efficacy and tolerability of octatropine methyl bromide plus diazepam (Valpinax) in patients with irritable bowel syndrome (IBS). MATERIALS AND METHODS: We conducted a randomized, double-blind, multicentre study in 186 patients aged 18-65 years with IBS diagnosed according to Rome II criteria. Following a 2-week washout period, patients received octatropine plus diazepam 40 mg/2.5 mg twice daily or placebo for 6 weeks. The primary efficacy endpoint was response to a weekly question: "did you have satisfactory relief of your abdominal pain and discomfort during the last week?" Other endpoints included abdominal swelling, abdominal pain and discomfort, symptom severity, and the number of bowel movements. A prespecified subgroup analysis was conducted in patients with an abdominal pain and discomfort score > or = 3. RESULTS: The primary efficacy endpoint showed a tendency towards a statistically significant benefit for octatropine plus diazepam over placebo among patients with a baseline abdominal pain and discomfort score of > or = 3 (3 vs. 0 patients; p = 0.059). Octatropine plus diazepam demonstrated significant improvements from baseline in all parameters assessed, but not compared with placebo. Adverse events were reported in 15.1% of patients receiving octatropine plus diazepam. CONCLUSIONS: Patients with IBS and an abdominal pain and discomfort score of > or = 3, who may be considered in the active phase of the disease, may derive some benefits from octatropine plus diazepam. This study highlights that Rome II criteria should be considered with particular care in the design of a clinical trial, since it does not consider disease activity level on admission.

Extraintestinal manifestations of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is associated with a variety of extraintestinal manifestations (EIMs) that may produce greater morbidity than the underlying intestinal disease and may even be the initial presenting symptoms of the IBD. As many as 36% of patients with IBD have at least one EIM. Some are more common related to active colitis (joint, skin, ocular, and oral manifestations). Others are especially seen with small bowel dysfunction (cholelithiasis, nephrolithiasis, and obstructive uropathy), and some are nonspecific disorders (osteoporosis, hepatobiliary disease, and amyloidosis). Patients with perianal Crohn's disease are at higher risk for developing EIMs than other IBD patients. Also the presence of one EIM appears to confer a higher likelihood of developing other manifestations than would be expected by chance alone. The identified pathogenetic autoimmune mechanisms include genetic susceptibility antigenic display of autoantigen, aberrant self-recognition, and immunopathogenetic autoantibodies against organ-specific cellular antigen(s) shared by colon and extra-colonic organs. Microbes may play an important role, probably by molecular mimicry. Early recognition of these extraintestinal manifestations should help guide therapy that will reduce overall morbidity in affected patients. This paper reviews the diagnosis, therapy and management of the more common EIMs.

Autologous haematopoietic stem cell transplantation without CD34+ cell selection in refractory Crohn's disease.

OBJECTIVES: Autologous haematopoietic stem cell transplantation (HSCT) with CD34(+) cell selection has recently been used in the treatment of refractory Crohn's disease, showing good safety and promising efficacy. We investigated the safety and efficacy of HSCT with unselected peripheral blood stem cells (PBSCs) in moderate-severe refractory Crohn's disease. PATIENTS: Four patients (three male, one female; age range 26-45 years) with active moderate-severe Crohn's disease (median Crohn's Disease Activity Index (CDAI) 319, range 272-345), refractory or intolerant to multiple drugs including infliximab, were enrolled. INTERVENTIONS: Unselected PBSCs were collected after mobilisation with cyclophosphamide (CTX) 1.5 g/m2 and granulocyte-colony stimulating factor (G-CSF) 10 microg/kg. The conditioning regimen included CTX 50 mg/kg on days -5 to -2 and rabbit anti-thymocyte globulin (ATG) 2.5 mg/kg on days -4 to -2. MAIN OUTCOME MEASURES: Primary endpoints were toxicity and clinical remission (CDAI<150) at 3 months. Secondary endpoints were clinical and endoscopic response at 3 months and toxicity, clinical and endoscopic remission at 12 months. RESULTS: No improvement or slight deterioration was observed following mobilisation (median CDAI 339, range 258-404). At the third month, the primary endpoint of clinical remission was achieved in all patients, with a median CDAI of 91 (range 56-102), and complete endoscopic remission was achieved in 2/3 patients. After a median follow-up of 16.5 months, 3/4 patients maintained both clinical and endoscopic remission, despite withdrawal of all drugs, and complete fistula closure was observed in all affected patients. No deaths or life-threatening infection occurred. Unexpected adverse events included a perianal abscess after mobilisation in one patient, pleural and pericardial effusions in another and BK virus-related macrohaematuria in another, all rapidly resolved with conservative treatment. CONCLUSION: Autologous HSCT with unselected PBSC appears to be safe and can induce and maintain remission in previously refractory Crohn's disease patients.

Imaging of perianal Crohn's disease.

Perianal fistulas and abscesses are common complications of Crohn's disease, affecting up to 50% of patients during their disease course. Accurate diagnosis and classification of perianal disease is crucial before and during treatment to plan an adequate approach for each patient and to avoid irreversible functional consequences. Although examination under anaesthesia has been considered the gold standard for diagnosis and classification of Crohn's disease perianal fistulas, taken alone it does not have perfect accuracy, stressing the need for concomitant or alternative, non-invasive, methods of evaluation. In this context, imaging modalities assessed for diagnosis, classification and monitoring of Crohn's disease perianal fistulas include pelvic magnetic resonance imaging, anorectal endoscopic ultrasonography, transcutaneous perianal ultrasound, fistulography and computed tomography. In particular, magnetic resonance imaging and endoscopic ultrasonography findings have shown the best accuracy, and the ability to influence therapeutic management of these patients. For transcutaneous perianal ultrasound too, good preliminary data have been reported. This paper reviews the available data on imaging methods for the management of perianal Crohn's disease.

Gastroesophageal reflux: the features in elderly patients.

AIM:To compare the features of gastroesophageal reflux disease between elderly and younger patients.METHODS:Twenty-four hour pH-monitoring and endoscopy were performed for the 66 elderly patients with typical gastroesophageal reflux symptoms, and the results were compared with 112 symptomatic younger patients.RESULTS:The results of 24-h pH-monitoring and endoscopy showed that the elderly patients had pathological reflux and reflux esophagitis more frequently than the younger patients. Percentage time with pH < 4 in elderly patients with reflux esophagitis was 32.5% in 24 hours, as compared with 12.9%in the younger patients with reflux esophagitis (P < 0.05). The elderly patients with reflux esophagitis have longer periods of acid reflux in both upright and supine-positions than the younger patients. Endoscopy showed that 20.8% of elderly patients had grade III/IV esophagitis, whereas only 3.4% of younger patients had grade III/IV esophagitis (P <0.002). Percentages of grades I/IIesophagitis in the two groups were 12.5% and 26.5%, respectively (P <0.002).CONCLUSION: Elderly patients, as compared with younger patients, have more severe gastroesophageal reflux and esophageal lesions. The incompetence of lower esophageal sphincter and the presence of hiatal hernia may be important factors leading to the difference in incidence and severity of reflux esoph agitis between elderly and younger patients.