Low testosterone elevates interleukin family cytokines in a rodent model: a possible mechanism for the potentiation of vascular disease in androgen-deficient males.

BACKGROUND: Androgen deficiency (AD) is associated with increased risk of atherosclerosis, cardiovascular, and peripheral arterial disease. Although the biochemical and molecular mechanisms underlying this risk remain unclear, higher testosterone (TST) levels correlate to significant immunoprotective molecular and cellular responses. Our group has previously demonstrated that female sex hormones influence vascular pathogenesis via inflammatory-modulated matrix metalloproteinase (MMP) regulation. Here we investigated the role of AD and androgen replacement therapy in the modulation of these hormonally responsive pathways that could be playing a role in the development of vascular pathogenesis. METHODS: Aged orchiectomized male rats underwent TST supplementation per controlled release pellet implantation (0-150 mg). Young and aged intact groups served as controls. Serum was collected at 0-4 wk and analyzed by enzyme-linked immunosorbent assays, qualitative cytokine screening, and quantitative multiplex analyses. Human aortic smooth muscle cells were treated with 4,5α-dihydrotestosterone (DHT; 0-3000 nM) before or after interleukin 1ß (IL-1ß; 5 ng/mL) stimulation. Quantitative polymerase chain reaction and in-gel zymography was used to assay the effect on MMP expression and activity. RESULTS: Subphysiological, physiological, and supraphysiological levels of TST were achieved with 0.5, 2.5, and 35 mg TST pellet implants in vivo, respectively. Inflammatory arrays indicated that interleukin cytokines, specifically IL-2, IL-6, IL-10, IL-12, and IL-13, were elevated at subphysiological level of TST, whereas TST supplementation decreased interleukins. Supraphysiological TST resulted in a significant increase in MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) in vivo. Pretreatment with IL-1ß slightly increased membrane type 1-MMP (MT1-MMP) and MMP-2 expression at low to mid-level DHT exposure in vitro, although these trends were not statistically significant. CONCLUSIONS: Here we demonstrate AD is a proinflammatory modulator and indicate that MMP-independent mechanisms may play a role downstream of AD-induced inflammatory signaling in dysfunctional vascular remodeling. Future in vivo studies will examine AD and TST supplementation in acute inflammatory response to vascular injury and in MMP-modulated vascular disease.

How medical alumni now see their junior clerkships in surgery.

The purpose of this study is to determine the effectiveness and value of the junior medical student surgical clerkship for physicians now in practice. Questionnaires were sent to all Mercer University School of Medicine alumni (1986-2007) using a five-point Likert scale. One hundred and fifty-seven responses were received from 873 recipients (18%), 71 per cent training in nonsurgical specialties. "Scrubbing in" on cases was the most valuable activity (82%), followed by faculty rounds (76%), resident work rounds (70%), and lectures (69%). Least useful activities were question and answer sessions (54%), grand rounds (53%), and morbidity and mortality conferences (57%). The amount of time in the operating room was appropriate for 61 per cent, but to 8 per cent the operating room was a waste of time. Faculty evaluations gave the most effective feedback (75%). Alumni in surgical specialties and obstetrics and gynecology rated their experiences higher than nonsurgical physicians. Overall, only 44 per cent saw the material learned as important to general medical education. Opinions regarding the value of surgical clerkships to current practices were mixed. Undergraduate surgical education should emphasize common surgical conditions, surgical decision-making, and simple procedures relevant to a nonsurgical practice.

After-hours complications: evaluation of the predictive accuracy of resident sign-out.

Resident duty-hour restrictions demand effective communication and teamwork in patient care. The process of resident sign-out is a potential source of miscommunication and medical error. Resident sign-out was followed over a 3-month period. Residents signing out to the night coverage team were asked to identify two patient groups: (1) problem patients who were especially ill and likely to present specific clinical problems; and (2) nonproblem patients who were likely not to be at risk for a problem requiring attention. Data on adverse events collected by the night float resident were classified into three categories: a problem predicted during sign-out in a problem patient, an unpredicted problem on a problem patient, and an unpredicted problem on all other patients. Resident sign-out accurately predicted only 42 per cent of adverse events. Only one third of major adverse events were predicted at checkout. One third of events occurred in patients identified at sign-out as being in the nonproblem group. The process of transfer of care must be standardized and individual practices reviewed to prevent error. Instruction on proper transfer of care and illustrations of potential points of breakdown should be given for all levels of training.

Endometrial stromal sarcoma development after hysterectomy and tamoxifen therapy.

Tamoxifen therapy is well known for its success in adjuvant therapy for breast carcinoma; however, despite its benefits, the agents' estrogenic influence on the uterus, and subsequent endometrial cell proliferation may result in development of invasive uterine tumors. It has been estimated that tamoxifen may increase the risk of endometrial-based cancer two- to threefold, but uterine sarcomas remain relatively rare, accounting for 2 to 5 per cent of all uterine malignancies. We report the case of a 72-year-old woman having received tamoxifen for a breast carcinoma and having a hysterectomy nearly 30 years prior who presented with an intra-abdominal, omentum-based mass that on excision was identified as an endometrial stromal sarcoma.