Clinical trial: the efficacy of open-label prucalopride treatment in patients with chronic constipation - follow-up of patients from the pivotal studies.

BACKGROUND: Prucalopride is approved in Europe for symptomatic treatment of chronic constipation in women with inadequate relief from laxatives. AIM: To evaluate efficacy of prucalopride during long-term treatment of patients with chronic constipation. METHODS: Patients from three pivotal double-blind, placebo-controlled, 12-week studies with prucalopride could continue treatment in open-label studies up to 24 months. Efficacy was evaluated every 3 months using the Patient Assessment of Constipation-Quality of Life (PAC-QOL) satisfaction scale. Laxative use and reasons for study discontinuation were recorded. RESULTS: Eighty-six percent of patients who completed the pivotal studies continued prucalopride treatment in the open-label studies (n = 1455, 90% female). Improvement in average PAC-QOL satisfaction score observed after 12-week, double-blind prucalopride was maintained during open-label treatment for up to 18 months; in each 3 month period, 40-50% of patients did not use any laxatives. Most frequent adverse events (AEs) resulting in discontinuation were gastrointestinal events (3.3%) and headache (1.0%). Only 10% of patients who had normalized bowel function on prucalopride at the end of pivotal trials discontinued due to insufficient response during open-label treatment. CONCLUSION: Satisfaction with bowel function is maintained for up to 18 months of treatment with prucalopride. Gastrointestinal events and headache cause discontinuation of prucalopride treatment in ∼5% of patients (ClinicalTrials.gov identifiers: NCT01070615 and NCT00987844).

L-tryptophan-induced eosinophilia-myalgia syndrome.

This report describes three Belgian cases of the eosinophilia-myalgia syndrome associated with the use of L-tryptophan-containing products. Three women, aged 51, 53 and 73 years, were taking L-tryptophan for 2 months to 2 years, at 500, 1500, and 2250 mg d-1, respectively. All developed disabling myalgias, fatigue, and a variable skin rash, in association with marked eosinophilia. In one patient, symptoms and eosinophilia reappeared after rechallenge with L-tryptophan. Discontinuation of the drug resulted in gradual disappearance of the symptoms, signs and laboratory abnormalities in two patients. One patient was treated with corticosteroids because of persisting myalgias. Because of the non-specific clinical manifestations, clinicians from all subspecialties of internal medicine might be confronted with such patients and should be aware of this new entity.

Value of transrectal ultrasonography in Crohn's disease.

Anorectal lesions are common and can develop silently in patients with Crohn's disease. Transrectal ultrasound examinations were performed to study 40 healthy individuals and 40 patients with Crohn's disease. A rigid linear endorectal probe was used to examine the rectal wall, the perirectal tissues, and the anal sphincter. In healthy individuals, the rectal wall showed five layers with a total diameter of maximum 4 mm. The anal sphincter was clearly visualized as an echo-poor and sharply delineated structure. No pathological lesions were detected perirectally. In Crohn's disease, an enlargement of the rectal wall was seen in 16 patients and heterogeneity of the anal sphincter in 19 patients. This technique detected lesions missed with the routine proctological examinations: four pararectal abscesses, two pararectal fistulas, two para-anal abscesses, and one para-anal fistula. In all examined subjects, the anal sphincter increased in breadth during squeezing and in length during straining. It is concluded that transrectal ultrasonography sharply delineates the rectal wall and the anal sphincter at rest and under dynamic conditions and detects unknown abscesses and fistulas in the pararectal and para-anal tissues in patients with Crohn's disease.

Transrectal ultrasound study of the pathogenesis of solitary rectal ulcer syndrome.

Transrectal ultrasonography is of clinical value in anorectal carcinoma and in inflammatory diseases of the anorectum. In this study a rigid linear endorectal probe was used to examine 15 patients with endoscopically and biopsy proved diagnosis of solitary rectal ulcer syndrome. In 13 of the 15 patients the rectal wall was thicker (mean (SEM) 5.7 (0.4) mm; normal values: 2.8 (0.1) mm) near the rectal ulcer. In all these cases the muscularis propria layer exceeded the maximum normal diameter of 2 mm. In nine of the 15 patients the normal rectal wall echo-structure, with five distinct layers, was disturbed and there was fading of the borders between the mucosa and the muscularis propria. Poor relaxation of the puborectalis muscle during straining was seen on ultrasound in 11 patients, as was intussusception of the rectal wall. The obvious enlargement of the muscularis propria points to a chronic mechanical load on the rectal wall. The ulcerative lesions are formed in this area of overloaded rectal wall. The direct visualisation of the puborectalis muscle during dynamic transrectal ultrasonography indicates that the fact that it does not relax is an important element in the pathogenesis of solitary rectal ulcer syndrome.

Is anorectal endosonography valuable in dyschesia?

AIMS: Dyschesia can be provoked by inappropriate defecation movements. The aim of this prospective study was to demonstrate dysfunction of the anal sphincter and/or the musculus (m.) puborectalis in patients with dyschesia using anorectal endosonography. METHODS: Twenty consecutive patients with a medical history of dyschesia and a control group of 20 healthy subjects underwent linear anorectal endosonography (Toshiba models IUV 5060 and PVL-625 RT). In both groups, the dimensions of the anal sphincter and the m. puborectalis were measured at rest, and during voluntary squeezing and straining. Statistical analysis was performed within and between the two groups. RESULTS: The anal sphincter became paradoxically shorter and/or thicker during straining (versus the resting state) in 85% of patients but in only 35% of control subjects. Changes in sphincter length were statistically significantly different (p<0.01, chi(2) test) in patients compared with control subjects. The m. puborectalis became paradoxically shorter and/or thicker during straining in 80% of patients but in only 30% of controls. Both the changes in length and thickness of the m. puborectalis were significantly different (p<0.01, chi(2) test) in patients versus control subjects. CONCLUSIONS: Linear anorectal endosonography demonstrated incomplete or even absent relaxation of the anal sphincter and the m. puborectalis during a defecation movement in the majority of our patients with dyschesia. This study highlights the value of this elegant ultrasonographic technique in the diagnosis of "pelvic floor dyssynergia" or "anismus".