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The effects of androgen precursors, combined with herbal extracts designed to enhance testosterone formation and reduce conversion of androgens to estrogens was studied in young men. Subjects performed 3 days of resistance training per week for 8 weeks. Each day during Weeks 1, 2, 4, 5, 7, and 8, subjects consumed either placebo (PL; n = 10) or a supplement (ANDRO-6; n = 10), which contained daily doses of 300 mg androstenedione, 150 mg DHEA, 750 mg Tribulus terrestris, 625 mg Chrysin, 300 mg Indole-3-carbinol, and 540 mg Saw palmetto. Serum androstenedione concentrations were higher in ANDRO-6 after 2, 5, and 8 weeks (p < .05), while serum concentrations of free and total testosterone were unchanged in both groups. Serum estradiol was elevated at Weeks 2, 5, and 8 in ANDRO-6 (p < .05), and serum estrone was elevated at Weeks 5 and 8 (p < .05). Muscle strength increased (p < .05) similarly from Weeks 0 to 4, and again from Weeks 4 to 8 in both treatment groups. The acute effect of one third of the daily dose of ANDRO-6 and PL was studied in 10 men (23 +/- 4 years). Serum androstenedione concentrations were elevated (p < .05) in ANDRO-6 from 150 to 360 min after ingestion, while serum free or total testosterone concentrations were unchanged. These data provide evidence that the addition of these herbal extracts to androstenedione does not result in increased serum testosterone concentrations, reduce the estrogenic effect of androstenedione, and does not augment the adaptations to resistance training. [ABSTRACT FROM AUTHOR]

Although plyometrics are widely used in athletic conditioning, the acute physiologic responses to plyometrics have not been described. The purpose of this study was to investigate the oxygen consumption, heart rate, and blood lactate responses to a single session of plyometric depth jumps. Twenty recreationally trained college-aged subjects (10 men, 10 women) participated in a single session of 8 sets of 10 box depth jumps from a height of 0.8 m with 3 minutes of passive recovery between each set. Plyometric depth jumping elicited 82.5 +/- 3.1% and 77.8 +/- 3.1% of the measured maximal oxygen consumption (VO(2)max) for women and men, respectively, with no difference in oxygen consumption in ml/kg/min or percent VO(2)max between sexes or sets. Heart rate significantly increased (p < 0.05) from 68.1 +/- 2.9 beats x min(-1) at rest to 169.6 +/- 1.2 beats x min(-1) during depth jumping. Sets 5 to 8 elicited a higher (p < 0.05) heart rate (173.3 +/- 1.3 beats x min(-1)) than sets 1 to 4 (164.6 +/- 1.8 beats x min(-1)). Women exhibited a higher heart rate (p < 0.05) during sets 1 and 2 (169.9 +/- 2.8 beats x min(-1)) than men (150.7 +/- 4.4 beats x min(-1)). The blood lactate concentrations were significantly (p < 0.05) increased above resting throughout all sets (1.0 +/- 0.2 mmol x L(-1) compared with 2.9 +/- 0.1 mmol x L(-1)), with no differences between sexes or sets. Plyometric depth jumping significantly increased oxygen consumption, heart rate, and blood lactate in both men and women, but no significant difference was found between the sexes. Plyometric depth jumping from a height of 0.8 m has similar energy system requirements to what Wilmore and Costill termed 'Aerobic Power' training, which should enhance VO(2)max, lactate tolerance, oxidative enzymes, and lactate threshold. [ABSTRACT FROM AUTHOR]

Because of the good initial fixation strength of interference screws used in anterior cruciate ligament reconstruction, metal interference screws have become the standard method for fixation of bone-patellar tendon-bone grafts. To avoid some of the complications with metal screws, a bioabsorbable interference screw was developed. Data on fixation strength in older human cadavers indicate a similar failure strength between bioabsorbable and metal screws. We studied the failure mechanisms, insertion torques, and fixation strengths of absorbable and metal interference screws in cadaveric knees from young and middle-aged donors. With identical gap and screw size, the mean insertion torque for the metal screws (mean, 1.5 N-m; SD, 0.8) was significantly higher than for the absorbable screws (mean, 0.3 N-m; SD, 0.19). The mean failure load for the metal screws (mean 640 N; SD, 201) was also significantly higher than for the absorbable screws (mean, 418 N; SD, 118). [ABSTRACT FROM AUTHOR]

This study shows a comprehensive simulation of water and sediment fluxes from the catchment to the reach scale. We describe the application of a modelling cascade in a well researched study catchment through connecting stateof- the-art public domain models in ArcGIS. Three models are used consecutively: (1) the hydrological model SWAT to evaluate water balances, sediment input from fields and tile drains as a function of catchment characteristics; (2) the onedimensional hydraulic model HEC-RAS to depict channel erosion and sedimentation along a 9 km channel onedimensionally; and (3) the two-dimensional hydraulic model AdH for simulating detailed substrate changes in a 230 m long reach section over the course of one year. Model performance for the water fluxes is very good, sediment fluxes and substrate changes are simulated with good agreement to observed data. Improvement of tile drain sediment load, simulation of different substrate deposition events and carrying out data sensitivity tests are suggested as future work. Main advantages that can be deduced from this study are separate representation of field, drain and bank erosion processes; shown adaptability to lowland catchments and transferability to other catchments; usability of the model’s output for habitat assessments.

Abstract Background Ezatiostat, a glutathione S-transferase P1-1 inhibitor, promotes the maturation of hematopoietic progenitors and induces apoptosis in cancer cells. Results Ezatiostat was administered to 19 patients with non-deletion(5q) myelodysplastic syndrome (MDS) at one of two doses (2000 mg or 2500 mg/day) in combination with 10 mg of lenalidomide on days 1–21 of a 28-day cycle. No unexpected toxicities occurred and the incidence and severity of adverse events (AEs) were consistent with that expected for each drug alone. The most common non-hematologic AEs related to ezatiostat in combination with lenalidomide were mostly grade 1 and 2 fatigue, anorexia, nausea, diarrhea, and vomiting; hematologic AEs due to lenalidomide were thrombocytopenia, neutropenia, and anemia. One of 4 evaluable patients (25%) in the 2500/10 mg dose group experienced an erythroid hematologic improvement (HI-E) response by 2006 MDS International Working Group (IWG) criteria. Four of 10 evaluable patients (40%) in the 2000 mg/10 mg dose group experienced an HI-E response. Three of 7 (43%) red blood cell (RBC) transfusion-dependent patients became RBC transfusion independent, including one patient for whom prior lenalidomide monotherapy was ineffective. Three of 5 (60%) thrombocytopenic patients had an HI-platelet (HI-P) response. Bilineage HI-E and HI-P responses occurred in 3 of 5 (60%), 1 of 3 with HI-E and HI-N (33%), and 1 of 3 with HI-N and HI-P (33%). One of 3 patients (33%) with pancytopenia experienced a complete trilineage response. All multilineage responses were observed in the 2000/10 mg doses recommended for future studies. Conclusions The tolerability and activity profile of ezatiostat co-administered with lenalidomide supports the further development of ezatiostat in combination with lenalidomide in MDS and also encourages studies of this combination in other hematologic malignancies where lenalidomide is active. Trial registration Clinicaltrials.gov: NCT01062152

Abstract Idiopathic chronic neutropenia (ICN) describes a heterogeneous group of hematologic diseases characterized by low circulating neutrophil levels often associated with recurrent fevers, chronic mucosal inflammation, and severe systemic infections. The severity and risk of complications, including serious infections, are inversely proportional to the absolute neutrophil count (ANC), with the greatest problems occurring in patients with an ANC of less than 0.5 × 109/L. This case report describes a 64-year-old female with longstanding rheumatoid arthritis who subsequently developed ICN with frequent episodes of sepsis requiring hospitalization and prolonged courses of antibiotics over a 4-year period. She was treated with granulocyte colony stimulating factors (G-CSF) but had a delayed, highly variable, and volatile response. She was enrolled in a clinical trial evaluating the oral investigational agent ezatiostat. Ezatiostat, a glutathione S-transferase P1-1 inhibitor, activates Jun kinase, promoting the growth and maturation of hematopoietic progenitor stem cells. She responded by the end of the first month of treatment with stabilization of her ANC (despite tapering and then stopping G-CSF), clearing of fever, and healing of areas of infection. This ANC response to ezatiostat treatment has now been sustained for over 8 months and continues. These results suggest potential roles for ezatiostat in the treatment of patients with ICN who are not responsive to G-CSF, as an oral therapy alternative, or as an adjunct to G-CSF, and further studies are warranted.

Abstract There remains considerable discontent between globalization scholars about how to conceptualize its meaning and in regards to epistemological and methodological questions concerning how we can come to understand how these processes ultimately operate, intersect and transform our lives. This article argues that to better understand what globalization is and how it affects issues such as global health, we must take a differentiating approach, which focuses on how the multiple processes of globalization are encountered and informed by different social groups and with how these encounters are experienced within particular contexts. The article examines the heuristic properties of qualitative field research as a means to help better understand how the intersections of globalization are manifested within particular locations. To do so, the article focuses on three recent case studies conducted on globalization and HIV/AIDS and explores how these cases can help us to understand the contextual permutations involved within the processes of globalization.

Abstract Background Canfosfamide is a novel glutathione analog activated by glutathione S-transferase P1-1. This study evaluated the safety and efficacy of canfosfamide in combination with pegylated liposomal doxorubicin (PLD) in patients with platinum resistant ovarian cancer. Patients with platinum resistant ovarian carcinoma and measurable disease received canfosfamide at 960 mg/m2 in combination with PLD at 50 mg/m2, intravenously day 1 in every 28 day cycles until tumor progression or unacceptable toxicities. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS). Results Canfosfamide plus PLD combination therapy was administered at 960/50 mg/m2, respectively. Thirty-nine patients received a median number of 4 cycles (range 1.0-18.0). The ORR was 27.8% (95% CI, 14.2-45.2) with a disease stabilization rate of 80.6% (95% CI, 64.0-91.8) in the evaluable population. The CA-125 marker responses correlated with the radiological findings of complete response or partial response. The median PFS was 6.0 months (95% CI, 4.2-7.9) and median survival was 17.8 months. The combination was well tolerated. Myelosuppression was managed with dose reductions and growth factor support. Grade 3 febrile neutropenia was observed in 2 patients (5.1%). Non-hematologic adverse events occurred at the expected frequency and grade for each drug alone, with no unexpected or cumulative toxicities. Conclusions Canfosfamide in combination with PLD is well tolerated and active in platinum and paclitaxel refractory or resistant ovarian cancer. A randomized phase 3 study was conducted based on this supportive phase 2 study. Trial Registration This study was registered at www.clinicaltrials.gov: NCT00052065.

Abstract Background A meta-analysis suggested the use of rosiglitazone was associated with an increased risk for cardiovascular (CV) events. Rosiglitazone remained available for use as more definitive safety trials were ongoing. This issue was reported in the lay media. Objective To review lay media articles to determine the extent of media coverage, the nature of the messaging, and to assess the quality of reporting. Methods The Factiva media database was used to identify articles published between May 18 and August 31, 2007. Two reviewers (a lay person and a physician) screened full text articles for eligibility, appraised the articles for their tone (worrisome, neutral, not worrisome), and for the quality of medical data reporting. Results The search identified 156 articles, 95 of which were eligible for our review. Agreement between the lay and medical reviewers in the appraisal of the article tone was 67.4%. Among those with agreement, the articles were often appraised as "worrisome" (75.3%). Among those with disagreement, the lay reviewer was significantly more likely to appraise articles as worrisome compared to the medical reviewer (77.4% vs. 3.2%, X2 = 9.11, P = 0.003). Cardiovascular risk was discussed in 91.6% of the articles, but risk was often reported in qualitative or relative terms. Conclusion There were many lay media articles addressing the safety of rosiglitazone, and the general messaging of these articles was considered "worrisome" by reviewers. Quality of risk reporting in the articles reviewed was poor. The impact of such media coverage on public anxiety and confidence in treatment should be explored.

Abstract Background Ezatiostat hydrochloride liposomes for injection, a glutathione S-transferase P1-1 inhibitor, was evaluated in myelodysplastic syndrome (MDS). The objectives were to determine the safety, pharmacokinetics, and hematologic improvement (HI) rate. Phase 1-2a testing of ezatiostat for the treatment of MDS was conducted in a multidose-escalation, multicenter study. Phase 1 patients received ezatiostat at 5 dose levels (50, 100, 200, 400 and 600 mg/m2) intravenously (IV) on days 1 to 5 of a 14-day cycle until MDS progression or unacceptable toxicity. In phase 2, ezatiostat was administered on 2 dose schedules: 600 mg/m2 IV on days 1 to 5 or days 1 to 3 of a 21-day treatment cycle. Results 54 patients with histologically confirmed MDS were enrolled. The most common adverse events were grade 1 or 2, respectively, chills (11%, 9%), back pain (15%, 2%), flushing (19%, 0%), nausea (15%, 0%), bone pain (6%, 6%), fatigue (0%, 13%), extremity pain (7%, 4%), dyspnea (9%, 4%), and diarrhea (7%, 4%) related to acute infusional hypersensitivity reactions. The concentration of the primary active metabolites increased proportionate to ezatiostat dosage. Trilineage responses were observed in 4 of 16 patients (25%) with trilineage cytopenia. Hematologic Improvement-Erythroid (HI-E) was observed in 9 of 38 patients (24%), HI-Neutrophil in 11 of 26 patients (42%) and HI-Platelet in 12 of 24 patients (50%). These responses were accompanied by improvement in clinical symptoms and reductions in transfusion requirements. Improvement in bone marrow maturation and cellularity was also observed. Conclusion Phase 2 studies of ezatiostat hydrochloride liposomes for injection in MDS are supported by the tolerability and HI responses observed. An oral formulation of ezatiostat hydrochloride tablets is also in phase 2 clinical development. Trial Registration Clinicaltrials.gov: NCT00035867