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Neural compensations occurring after prenatal cocaine exposure may often permit some functional recovery, although the cost of this reorganization may be a decrease in adaptability. As we have seen in our rodent model of prenatal cocaine exposure, latent deficits may become unmasked when offspring are exposed to cognitive and environmental demands and stressors. In adolescence and adulthood, offspring exposed gestationally to cocaine exhibit characteristic decreases in stress-induced immobility along with increases in aggression under the demands of social competition. Recently, we observed that cocaine-exposed offspring are also unusually sensitive to the long-term effects of early manipulation (noninvasive heart rate testing at 16 days of age). When tested in adulthood, cocaine-exposed offspring not receiving this early experience exhibited less immobility when tested in the presence of intermittent footshock or when subsequently examined in an open field as well as more locomotion in the open field than control offspring, findings reminiscent of previous work. By contrast, these effects were normalized (shock-induced immobility) or reversed (open field immobility and locomotion) in cocaine-exposed animals given the early experience. This marked susceptibility to the effects of early manipulation was less evident in control offspring and even in a group of stunted nutritional controls. Thus, cocaine-exposed offspring may exhibit increased sensitivity not only to environmental demands and stressors, but also to the potential moderating or beneficial effects of early experiences.

Calcitriol acts synergistically with carboplatin in preclinical models of adenocarcinoma of the prostate. The authors sought to test high-dose oral calcitriol in combination with carboplatin in patients with metastatic androgen-independent prostate cancer. Seventeen patients received oral calcitriol (0.5 microg/kg) on day 1 and intravenous carboplatin (AUC 7 or AUC 6 in patients with prior radiation) on day 2, repeated every 4 weeks. PSA response was the primary end point and was defined as a 50% reduction confirmed 4 weeks later. Palliative response (2-point reduction or normalization of pain on the present pain intensity [PPI] scale without increased analgesic consumption) was also examined. One of 17 patients (6%, 95% CI, 0-28) achieved a confirmed PSA response. Four patients (24%, 95% CI, 7-49) had PSA reductions ranging from 24 to 38%. Of the 15 patients with a PPI > or = 1 point on entry, 3 (18%, 95% CI, 4-48) met criteria for palliative response. Treatment-related toxicity was mild and generally similar to that expected with single-agent carboplatin. Despite encouraging preclinical evidence, the addition of oral calcitriol to carboplatin in this study was not associated with an increase in the response rate when compared with the reported activity of carboplatin alone.

Objectives-Hot flashes are a common adverse effect of hormonal therapy for prostate cancer. We sought to determine the effect of acupuncture on hot flash frequency and intensity, quality of life, and sleep quality.Methods-Men who had a hot flash score (HFS) > 4 while on androgen deprivation therapy for prostate cancer received acupuncture with electrostimulation biweekly for 4 weeks, then weekly for 6 weeks using a predefined treatment plan. The primary endpoint was a 50% reduction in HFS after 4 weeks of therapy, calculated from the patient daily hot flash diary. Hot flash related quality of life and sleep quality, and biomarkers potentially related to hot flashes, including serotonin, calcitonin gene-related peptide (CGRP), and urinary 5-HIAA were examined.Results-Twenty-five men were enrolled between 9/2003 and 4/2007; 22 were eligible and evaluable. After four weeks, 9 of 22 patients (41%, 95%CI 21 to 64%) had a > 50% reduction in HFS. Twelve of 22 patients (55%, 95%CI 32 to 76%) met this response definition at any time during the course of therapy. No patients had a significant increase in HFS on therapy. Reduced HFS was associated with improvement in hot flash related quality of life and sleep quality.Conclusions-Multiple placebo-controlled trials have demonstrated a 25% response rate to placebo treatment for hot flashes. 41% of patients responded by week 4 and 55% overall in this pilot study providing evidence of a potentially meaningful benefit. Further studies of acupuncture for hot flashes in this population are warranted.