Tramadol use is associated with enhanced postoperative outcomes in breast cancer patients: a retrospective clinical study with in vitro confirmation.

BACKGROUND: There is growing interest in the effect of postoperative analgesics on oncological outcomes after cancer surgery. We investigated the impact of tramadol after breast cancer surgery on recurrence and mortality and explored the mechanism by which tramadol affects cultured breast cancer cells in vitro. METHODS: Electronic medical records of patients who underwent breast cancer surgery between November 2005 and December 2010 at Severance Hospital in Korea were reviewed. Cox regression analyses were used to identify factors related to postoperative recurrence and mortality. We performed the sensitivity test with propensity score matching to adjust for selection bias. In addition, we investigated the effects of tramadol on human breast adenocarcinoma (Michigan Cancer Foundation-7 [MCF-7]) cells via assessment of cell viability, clonogenic assay, and cell cycle analysis in vitro. RESULTS: Of 2588 breast cancer patients, 36.4% had received tramadol. Those who received tramadol had a 0.71-fold decreased risk of recurrence and a 0.56-fold decrease in mortality. The MCF-7 cell viability assays showed that tramadol had an anti-proliferative effect by cell cycle arrest, suppressing colony formation, and regulation of oestrogen and progesterone receptors. Tramadol induced apoptosis of MCF-7 cells via extracellular signal-regulated kinases by decreasing of 5-hydroxytryptamine (HT)2B receptor and transient receptor potential vanilloid-1 expression. CONCLUSIONS: After breast cancer surgery, patients who received tramadol had a decreased risk of postoperative recurrence and mortality. The anti-tumour effect of tramadol appears to involve inhibition of proliferation, induction of apoptosis, and effects on 5-HT2B receptor and TRPV-1.

Dopamine precursor depletion impairs timing in healthy volunteers by attenuating activity in putamen and supplementary motor area.

Neuropsychological investigations of patients with Parkinson's disease, schizophrenia, or attention deficit disorder converge with psychopharmacological studies in animals and healthy volunteers to implicate dopamine (DA) pathways in timing. In parallel, single-cell recording and functional neuroimaging studies have highlighted the importance of basal ganglia, prefrontal cortex, and supplementary motor area (SMA) for timing. In a placebo-controlled, within-subject design, we combined event-related functional magnetic resonance imaging with a DA manipulation (acute phenylalanine/tyrosine depletion; APTD) in healthy volunteers to pinpoint the neuroanatomical and functional substrates of the DA modulation of timing. Behaviorally, APTD selectively impaired accuracy of perceptual timing, with no effect on performance of a color-control task matched for difficulty, working memory (WM), and attentional demands. Neurally, APTD attenuated timing-specific activity in the putamen and SMA. Notably, APTD-induced decreases in brain activity were directly correlated to APTD-induced impairments in timing performance. Moreover, APTD modulated timing-specific activity selectively during initial storage of the sample duration, but had no effect during its subsequent retrieval or comparison to a probe. Our results do not simply reflect DA modulation of WM since the color task controlled for the WM updating process necessary for timing of durations in the seconds range. Moreover, preliminary evidence indicated APTD effects on putamen and SMA were greater for subsecond (540 ms) than suprasecond (1080 ms) durations, when WM demands would actually be lower. Instead, we show for the first time in healthy humans that DA manipulation perturbs timing by attenuating the activity in putamen and SMA that mediates initial storage of temporal information into WM.

Evaluation of non-English dietary supplement advertisements in an ethnic minority community in America.

OBJECTIVE: The primary objective was to evaluate the rate at which non-English dietary supplement advertisements distributed in a sampled ethnic minority community are in compliance with the federal advertising regulations. The secondary objective was to assess the availability of supporting evidence to substantiate the advertised health claims. DESIGN: Cross-sectional study. SETTING: The contents of dietary supplement advertisements from the Los Angeles Korea Times and the Los Angeles Korea Daily were evaluated during the month of July 2005. After removing duplicate advertisements, the percentage of advertisements making prohibited disease claims and DSHEA (Dietary Supplement Health and Education Act) disclaimer statements was determined. The presence of data substantiating advertised claims was determined by requesting data from the manufacturers and browsing the manufacturers' websites. An observational technique was utilised for content analysis, and data analysis was conducted using quantitative descriptive statistics. RESULTS: Disease claims were present in 84.5%, while DHSEA disclaimer statements were present in only 18.4% of the advertisements. Data to substantiate the claims were provided by 53.4% of the manufacturers. The majority of the additional information consisted of repetition of the advertised claims and consumer testimonies. Experimental data were available for only 13.6% of the products. CONCLUSIONS: The high rate of non-compliance with federal regulations suggests a need for better oversight of non-English promotions of dietary supplements.