Clinical trial: dextofisopam in the treatment of patients with diarrhoea-predominant or alternating irritable bowel syndrome.

BACKGROUND: Dextofisopam modulates stimulated activity in animal models of stress, altered bowel motility, and visceral hypersensitivity. AIM: To evaluate the effects of dextofisopam in men and women with diarrhoea-predominant or alternating irritable bowel syndrome (IBS) (d-IBS or a-IBS). METHODS: In this double-blind, placebo-controlled study, patients were randomly assigned to receive dextofisopam 200 mg b.d. or placebo for 12 weeks. The prospectively defined primary endpoint was number of months of adequate overall relief of IBS symptoms. Bowel function was assessed primarily via stool frequency and consistency. RESULTS: Of 140 enrolled patients, 66 received dextofisopam and 74 placebo; 73% of the patients were women, and 78% had d-IBS. Dextofisopam was superior to placebo on the primary endpoint (P = 0.033). In d-IBS patients treated with dextofisopam, both men and women had improved stool consistency, but stool frequency was reduced only in women. Benefit diminished over time on the primary endpoint, but persisted on frequency and consistency. Dextofisopam and placebo had similar rates and types of adverse events, with more events of worsening abdominal pain with dextofisopam (12% vs. 4%) and more headaches with placebo (12% vs. 5%). Constipation was rare. CONCLUSION: Dextofisopam should be further evaluated as a new treatment for men and women with d-IBS and a-IBS.

Review article: the role of antibiotics vs. conventional pharmacotherapy in treating symptoms of irritable bowel syndrome.

BACKGROUND: The concept of augmenting the management of irritable bowel syndrome with antibiotics is evolving, and many questions remain regarding this therapy relative to known and hypothesized irritable bowel syndrome pathophysiology. The clinical evidence of small intestinal bacterial overgrowth as an important aetiology of irritable bowel syndrome continues to accumulate. Clinical symptoms of bacterial overgrowth and irritable bowel syndrome are similar; however, a definitive cause-and-effect relationship remains unproven. It is unclear whether motility dysfunction causes bacterial overgrowth or gas products of enteric bacteria affect intestinal motility in irritable bowel syndrome. AIM: To discusses the efficacy and tolerability of current symptom-directed pharmacotherapies and of antibiotics in the treatment of irritable bowel syndrome. METHODS: A computerized search of PubMed was performed with search terms "IBS", "pharmacotherapy" and "antibiotics". Relevant articles were selected, and the reference list of selected articles was reviewed to identify additional references. RESULTS: Antibiotic treatment benefits a subset of irritable bowel syndrome patients. The non-absorbed antibiotic rifaximin has a favourable safety and tolerability profile compared with systemic antibiotics and demonstrates a therapeutic efficacy comparable with symptom-based irritable bowel syndrome pharmacotherapies. CONCLUSION: Rifaximin is the only antibiotic with demonstrated sustained benefit beyond therapy cessation in irritable bowel syndrome patients in a placebo-controlled trial. Whether antibiotics can improve quality of life in patients with irritable bowel syndrome warrants further research.

Fanconi anemia: a model for genetic causes of abnormal brain development.

Fanconi anemia is an autosomal recessive disease resulting in bone-marrow failure, phenotypical abnormalities and predisposition to malignancy. The authors reviewed 257 clinical and neuropathology results from the International Fanconi Anemia Registry at The Rockefeller University. Two patients had hydrocephalus and ventriculoperitoneal shunts. Of 15 neuropathology reports, 10 found CNS abnormalities, with the most common--ventriculomegaly--seen in six, two of whom required shunts. Aqueductal stenosis, agenesis of the corpus callosum and septum pellucidum, and holoprosencephaly were found. The authors conclude that neurological derangements are probably more common in Fanconi anemia than previously recognised. Fanconi anemia cells in culture are highly sensitive to oxidative stress and alkylating agents; Fanconi anemia may provide a model for a genetic disorder potentially predisposing to environmental insults.

Fanconi's anaemia and pregnancy.

We have identified six new cases of Fanconi's anaemia (FA) who had pregnancies, and reviewed 11 others from the literature. At least 110 FA females have reached 16 years of age or more, of whom 15% became pregnant. There were a total of 26 pregnancies, resulting in 19 births and 18 surviving children. Anaemia and/or thrombocytopenia worsened during pregnancy in 10 patients, but five subsequently improved: seven had no haematological problems. Seven of the FA patients who had pregnancies died subsequently from cancer, and two from thrombocytopenic bleeding 3 and 20 years later. There were no peripartum deaths. Pregnancy in FA is clearly possible, with increased risks that are manageable from both the haematological and the obstetric aspects.