Alpha-adrenoreceptor reagents. 4. Resolution of some potent selective prejunctional alpha 2-adrenoreceptor antagonists

The resolution of three 2-substituted derivatives of idazoxan is described. The enantiomers show large separations in activity in a variety of in vitro and in vivo tests, and the active isomers are all potent and selective antagonists at the alpha 2-adrenoreceptor. The significance of these results in relation to those published on the enantiomers of idazoxan and to those on optically active alpha 2-adrenoreceptor agonists is discussed.     

Phase II trial of 10 deaza-aminopterin in patients with bladder cancer

Summary Deaza-aminopterin is a folate analog which is transported more rapidly than methotrexate into cells and appears to be more active than methotrexate against human and animal tumor in vitro. Fifteen patients with advanced urothelial tract cancer were given deaza-aminopterin 30–37.5 mg/m² IV QW. In responding patients drug was given QOW after 4–6 consecutive doses. Doses were escalated or de-escalated by 7.5 mg/m² depending on toxicity. Twelve patients had received prior chemotherapy which included methotrexate in nine. Three patients achieved a partial remission lasting 1, 3, and 3 months respectively: all responders had previously failed methotrexate after an initial response to a methotrexate containing regimen. None of the six patients who were methotrexate naive responded to deaza-aminopterin; 3 subsequently received methotrexate without response. Mild mucositis was universal and in 5 was severe. Six patients had an increase in liver transaminases probably secondary to anti-folate hepatotoxicity. Other toxicities included diarrhea, nausea, skin rash and fever. Further studies are needed to define the precise efficacy of deaza-aminopterin in patients with urothelial tract cancers.     

Defecation dynamics and behavior profiles in encopretic children

The social competence and behavioral profiles of 38 encopretic children were evaluated, and the social competence and behavioral ratings were correlated with physiologic abnormalities found during anorectal manometric and EMG evaluation and with treatment outcome. When defecation was studied, 66% of encopretic children were not able to defecate rectal balloons and 63% were not able to relax the external anal sphincter during defecation attempts. Total social competence and behavior problem scores were not different for boys able and unable to defecate balloons. Total social competence scores were significantly lower in girls unable to defecate balloons than in those able to (P less than .006), whereas behavior problem scores were similar in girls able to and unable to defecate. We found that persistence of encopresis at 6-month and 12-month follow-up was not related to the social competence (P greater than .2) or behavioral scores (P greater than .2) but was significantly related to the inability to defecate (P less than .01) and to the inability to relax the external sphincter during defecation attempts (P less than .03).