Prucalopride is effective in patients with severe chronic constipation in whom laxatives fail to provide adequate relief. Results of a double-blind,placebo-controlled clinical trial

BACKGROUND: Chronic constipation (CC) is common and there is a need for more effective and better-tolerated agents that normalize bowel function without affecting secretion. Prucalopride is a novel, selective serotonin(4) receptor agonist with enterokinetic properties. AIMS: Pilot study to compare the efficacy and tolerability of prucalopride and placebo in patients with severe CC referred to a tertiary centre. METHODS: After 4-weeks' run in, patients were randomized to 4 weeks' once daily, double-blind treatment with either prucalopride 4 mg (n = 27) or placebo (n = 26). A 50% dose reduction after 2 weeks' treatment was possible for patients with an excessive gastrointestinal response to the study medication (severe cramps, abdominal pain, and diarrhea). Patients assessed efficacy using a visual analogue scale (VAS) and recorded bowel function in daily diaries. The investigator assessed efficacy and total gut transit time (marker study). RESULTS: Patient VAS assessment demonstrated that prucalopride was significantly more effective than placebo in softening stools, and decreasing straining and time to first stool. Prucalopride also had a positive effect on stool frequency, feeling of complete evacuation and total gut transit time, although these differences were not statistically significant compared with placebo. The most common adverse events were gastrointestinal symptoms and headache; most were mild to moderate. There were no clinically relevant effects on cardiovascular or laboratory parameters. CONCLUSIONS: Once-daily prucalopride 4 mg for 4 weeks is effective and well tolerated in patients with severe CC. It improves whole gut transit, reducing straining, softening stools and reducing time to first bowel movement.     

Appropriateness of angiography for suspected coronary artery disease

The aim of this study was to assess the appropriate use of diagnostic catheterizations (DC) for the patients with suspected coronary artery disease performed in Iran. The Electronic Health Record System database and manual review of files were utilised to collect data between 2012 and 2014. Patients were categorized in three groups as appropriate, uncertain, and inappropriate usage of DC and the logistic regression was used to investigate the relationships between variables. One-quarter of the 2458 angiographies were rated as inappropriate, out of which 99% had no previous stress test. The rate of inappropriate DC between various hospitals were approximately the same. The regression showed that some risk factors (Sex, high cholesterol, smoking, chronic heart failure, renal failure, diabetes) were significantly associated with inappropriate rate.     

Lymphocytic Hypophysitis Masking a Suprasellar Germinoma in a 12-year-old Girl<197>A Case Report

Case history, light and electron microscopic findings of a case of a lymphocytic hypophysitis in coincidence with a suprasellar germinoma in a 12-year-old girl are reported. The girl presented with a long time case history of diabetes insipidus and subsequent panhypopituitarism. Two years after the diagnosis of diabetes insipidus magnetic resonance imaging (MRI) showed a tumorous enlargement of the sellar content and pituitary stalk. A transnasal exploration was initially performed and revealed a lymphocytic hypophysitis. Light microscopy showed a dense infiltration of mature lymphocytes and plasma cells in the interstitium of the anterior pituitary gland. The stalk area could not be exposed to exclude a germinoma. One year later the lesion relapsed despite dexamethason therapy and a second operation by another neurosurgeon had to be performed. Light microscopy showed lymphocytic infiltrates, fibrosis and necrosis. The diagnosis was a lymphocytic hypophysitis again. Though transcranially exposed only pituitary tissue was removed. No infundibular mass became visible at surgery as shown by MRI. The girl developed five months later multiple cerebral lesions, which revealed to be a germinoma. Lymphocytic hypophysitis in children is very rare and a coincedence with a germinoma has not been described from histopathological aspect until now. The origin of the pituitary infiltration is discussed.     

Pharmacokinetics and Toxicity of Sodium Selenite in the Treatment of Patients with Carcinoma in a Phase I Clinical Trial: The SECAR Study

Background: Sodium selenite at high dose exerts antitumor effects and increases efficacy of cytostatic drugs in multiple preclinical malignancy models. We assessed the safety and efficacy of intravenous administered sodium selenite in cancer patients’ refractory to cytostatic drugs in a phase I trial. Patients received first line of chemotherapy following selenite treatment to investigate altered sensitivity to these drugs and preliminary assessment of any clinical benefits. Materials and Methods: Thirty-four patients with different therapy resistant tumors received iv sodium selenite daily for consecutive five days either for two weeks or four weeks. Each cohort consisted of at least three patients who received the same daily dose of selenite throughout the whole treatment. If 0/3 patients had dose-limiting toxicities (DLTs), the study proceeded to the next dose-level. If 2/3 had DLT, the dose was considered too high and if 1/3 had DLT, three more patients were included. Dose-escalation continued until the maximum tolerated dose (MTD) was reached. MTD was defined as the highest dose-level on which 0/3 or 1/6 patients experienced DLT. The primary endpoint was safety, dose-limiting toxic effects and the MTD of sodium selenite. The secondary endpoint was primary response evaluation. Results and Conclusion: MTD was defined as 10.2 mg/m², with a calculated median plasma half-life of 18.25 h. The maximum plasma concentration of selenium from a single dose of selenite increased in a nonlinear pattern. The most common adverse events were fatigue, nausea, and cramps in fingers and legs. DLTs were acute, of short duration and reversible. Biomarkers for organ functions indicated no major systemic toxicity. In conclusion, sodium selenite is safe and tolerable when administered up to 10.2 mg/m² under current protocol. Further development of the study is underway to determine if prolonged infusions might be a more effective treatment strategy.