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Background Erectile dysfunction (ED) may be one manifestation of a generalized vascular disorder characterized by endothelial dysfunction. Statin drugs may improve endothelial function, even before altering the lipid profile. Objective We sought to determine whether the addition of a statin with sildenafil would improve ED in men who initially responded poorly to sildenafil. Methods Men with moderate‐to‐severe ED despite an adequate sildenafil trial were enrolled in this randomized, double‐blind, placebo‐controlled pilot study. ED was defined using a validated self‐administered questionnaire as a score of ≤16 on the International Index of Erectile Function (erectile function domain score range of 6–30). Improvement in ED score with sildenafil was reassessed at 6 and 12 weeks of treatment with atorvastatin (80 mg daily) or matching placebo. Results Twelve men (mean age 58 ± 13 years) with a mean domain score of 8.2 ± 6.9 and a mean duration of ED of 3.7 years were enrolled in the study. Treatment with atorvastatin decreased mean low‐density lipoprotein cholesterol by 43% and resulted in an improvement with sildenafil in domain score of 7.8 ( P = 0.036); an effect was apparent by 6 weeks. The increase in domain score in placebo patients was not statistically significant. Conclusions Treatment with atorvastatin improved sexual function and the response to oral sildenafil in men who did not initially respond to treatment with sildenafil. The results of this pilot study support the hypothesis that vascular endothelial dysfunction contributes to ED in sildenafil nonresponders and deserves further testing in a large clinical trial. Herrmann HC, Levine LA, Macaluso J Jr, Walsh M, Bradbury D, Schwartz S, Mohler ER III, and Kimmel SE. Can atorvastatin improve the response to sildenafil in men with erectile dysfunction not initially responsive to sildenafil? Hypothesis and pilot trial results. J Sex Med 2006;3:303–308.

The theoretical role of sigma receptors in psychosis has led to the development of selective sigma receptor ligands as potential antipsychotic agents. BMY 14802 has its most potent binding at the sigma binding site, with some degree of serotonin subtype 1A and negligible dopamine receptor binding. It is atypical of standard neuroleptics in that it does not induce catalepsy in rats. It has been shown to have efficacy in animal models of psychosis. It was hypothesized that the drug would have antipsychotic effects in humans without producing the extrapyramidal side effects typical of standard neuroleptics. We report here the results of an uncontrolled, multicenter safety and efficacy study of patients with acute exacerbations of schizophrenia treated with BMY 14802. After 1 week of single-blind placebo treatment, 28 patients were treated with BMY 14802 (up to 3000 mg/day) for up to 4 weeks. There was no significant improvement in psychiatric symptoms, as measured by the total Brief Psychiatric Rating Scale scores or Clinical Global Improvement. There were no changes in involuntary movements, as measured by the Abnormal Involuntary Movement Scale, or in extrapyramidal symptoms as measured by the Simpson-Angus Scale.

Erectile dysfunction (ED) may be one manifestation of a generalized vascular disorder characterized by endothelial dysfunction. Statin drugs may improve endothelial function, even before altering the lipid profile.We sought to determine whether the addition of a statin with sildenafil would improve ED in men who initially responded poorly to sildenafil.Men with moderate-to-severe ED despite an adequate sildenafil trial were enrolled in this randomized, double-blind, placebo-controlled pilot study. ED was defined using a validated self-administered questionnaire as a score ofor=16 on the International Index of Erectile Function (erectile function domain score range of 6-30). Improvement in ED score with sildenafil was reassessed at 6 and 12 weeks of treatment with atorvastatin (80 mg daily) or matching placebo.Twelve men (mean age 58 +/- 13 years) with a mean domain score of 8.2 +/- 6.9 and a mean duration of ED of 3.7 years were enrolled in the study. Treatment with atorvastatin decreased mean low-density lipoprotein cholesterol by 43% and resulted in an improvement with sildenafil in domain score of 7.8 (P = 0.036); an effect was apparent by 6 weeks. The increase in domain score in placebo patients was not statistically significant.Treatment with atorvastatin improved sexual function and the response to oral sildenafil in men who did not initially respond to treatment with sildenafil. The results of this pilot study support the hypothesis that vascular endothelial dysfunction contributes to ED in sildenafil nonresponders and deserves further testing in a large clinical trial.

The optimal management of lower pole renal calculi is controversial. We compared shock wave lithotripsy (SWL) and ureteroscopy (URS) for the treatment of patients with small lower pole stones in a prospective, randomized, multicenter trial.A total of 78 patients with 1 cm or less isolated lower pole stones were randomized to SWL or URS. The primary outcome measure was stone-free rate on noncontrast computerized tomography at 3 months. Secondary outcome parameters were length of stay, complication rates, need for secondary procedures and patient derived quality of life measures.A total of 67 patients randomized to SWL (32) or URS (35) completed treatment. The 2 groups were comparable with respect to age, sex, body mass index, side treated and stone surface area. Operative time was significantly shorter for SWL than URS (66 vs 90 minutes). At 3 months of followup 26 and 32 patients who underwent SWL and URS had radiographic followup that demonstrated a stone-free rate of 35% and 50%, respectively (p not significant). Intraoperative complications occurred in 1 SWL case (unable to target stone) and in 7 URS cases (failed access in 5 and perforation in 2), while postoperative complications occurred in 7 SWL and 7 URS cases. Patient derived quality of life measures favored SWL.This study failed to demonstrate a statistically significant difference in stone-free rates between SWL and URS for the treatment of small lower pole renal calculi. However, SWL was associated with greater patient acceptance and shorter convalescence.

In Reply.— We appreciate the work of Drs Meltzer et al. They suggest that the reasons for the discrepant results between our two reports lie in the smaller number of subjects and the absence of a placebo-control in our study. While the number of subjects in our study was small, an additional subject who received a dl-pindolol dose of 20 mg (not 5 mg or 10 mg) demonstrated a nearly 50% reduction in buspirone-PRL release. In addition, data from a dose-response study of dl-pindolol challenge alone in the one subject who displayed no suppression of buspirone-PRL release with the dl-pindolol dose of 20 mg, revealed a 187% peak increase over baseline in PRL release (ie, 10.6 μg/L at baseline, and 19.7 μg/L peak change from baseline) when challenged with 20 mg of dl-pindolol. Hence, it is possible for dl-pindolol to suppress a PRL response associated with buspirone

To the Editor.— The role of serotonin 1 (5-HT-1—like) receptors in the action of psychopharmacologic agents and in psychiatric disorders is an increasing focus of research. 1 However, there are few agents available for clinical use that assess the function of 5-HT-1—like receptors in humans. Buspirone hydrochloride (Buspar), a nonbenzodiazepine compound currently marketed as an anxiolytic, is reported to have high affinity for the central 5-HT-la receptor. 2 Hence, examination of neuroendocrine responses (eg, prolactin [PRL], growth hormone [GH], corticotropin [ACTH], cortisol [CORT]) to acute challenge with buspirone 3-6 may enable an assessment of 5-HT-la receptor sensitivity in humans. 3 However, since buspirone is reported to have antidopamine activity in some, 7 although not all, 8 studies, the PRL response to buspirone challenge, in particular, may be confounded by its action on central dopaminergic neurons. In fact, some have suggested that the PRL response to buspirone challenge is due to