Citations

Purpose This study evaluates the safety and efficacy of plerixafor (AMD3100), a CXCR4 antagonist, in mobilizing hematopoietic stem cells for autologous stem-cell transplantation in non-Hodgkin's lymphoma (NHL) patients. Patients and Methods This is a phase III, multicenter, randomized (1:1), double-blind, placebo-controlled study. Patients with non-Hodgkin's lymphoma requiring an autologous hematopoietic stem-cell transplantation in first or second complete or partial remission were eligible. Patients received granulocyte colony-stimulating factor (G-CSF; 10 μg/kg) subcutaneously daily for up to 8 days. Beginning on evening of day 4 and continuing daily for up to 4 days, patients received either plerixafor (240 μg/kg) or placebo subcutaneously. Starting on day 5, patients began daily apheresis for up to 4 days or until ≥ 5 × 10 6 CD34+ cells/kg were collected. The primary end point was the percentage of patients who collected ≥ 5 × 10 6 CD34+ cells/kg in 4 or fewer apheresis days. Results This report presents all data for all patients (n = 298) through 12 months follow-up. Eighty-nine (59%) of 150 patients in the plerixafor group and 29 (20%) of 148 patients in the placebo group met the primary end point (P < .001). One hundred thirty-five patients (90%) in plerixafor group and 82 patients (55%) in placebo group underwent transplantation after initial mobilization. Median time to engraftment was similar in both groups. The most common plerixafor-associated adverse events were GI disorders and injection site reactions. Conclusion Plerixafor and G-CSF were well tolerated and resulted in a significantly higher proportion of patients with non-Hodgkin's lymphoma achieving the optimal CD34+ cell target for transplantation in fewer apheresis days, compared with G-CSF alone.

ABSTRACT Introduction The presence of erectile or ejaculatory dysfunction may indicate physical problems; however, individual perceptions (e.g., sexual satisfaction) may reflect the degree of concern about these changes. Long-term data showing how changes in multiple sexual function domains track together may be useful in understanding the importance of physical declines vs. sexual satisfaction. Aim The aim of this study was to describe changes in sexual function among a population-based sample of aging men. Methods A population-based cohort study using data from the Olmsted County Study of Urinary Symptoms and Health Status among Men. Sexual function was assessed biennially from 1996 to 2004 using a previously validated questionnaire in a random sample of 2,213 men. Main Outcome Measures Changes in erectile function, libido, ejaculatory function, sexual problems, and sexual satisfaction. Results Overall, we observed declines in all of the sexual function domains, ranging from an annual decrease of 0.03 point per year for sexual satisfaction to an annual decrease of 0.23 point per year in erectile function. Moderate correlations were observed among all longitudinal changes in sexual function (range in age-adjusted rs = 0.14–0.43); however, significantly smaller correlations between changes in the functional domains and changes in sexual satisfaction and problem assessment were observed among older men (range in age-adjusted rs = 0.03–0.29). Conclusion Overall, these results demonstrate that longitudinal changes in five sexual function domains change together over time in our community-based cohort. Erectile function, ejaculatory function, and sexual drive decrease over time with greater rates of decline for older men. However, older men may be less likely to perceive these declines as a problem and be dissatisfied. These data may prove helpful to patients and clinicians in understanding and discussing changes in multiple aspects of sexual function.

Abstract Prostate cancer is the second leading cause of cancer deaths among U.S. men. Early detection is associated with drastically improved 5-year survival rates. It is unclear, however, what psychosocial factors motivate or discourage men from taking advantage of both prostate-specific antigen (PSA) testing and digital rectal examination (DRE). The goal of the current study was to identify psychosocial factors that influence screening behavior for prostate cancer in a cohort of 2,447 men. In 1990, a randomly selected cohort of Caucasian men, ages 40 to 79 years, from Olmsted County, Minnesota, were enrolled in the study. These men completed a questionnaire containing queries on family history of prostate cancer, concern about getting prostate cancer, and marital status. Medical and laboratory records were reviewed to determine the number DREs (1989-1996) and PSA tests (1989-1998). Frequent screening was defined as the upper 25th percentile for number of DREs (&gt;4) or PSAs (&gt;3). Men who have a family history and men who worry or have concern about prostate cancer were more likely [odds ratio (OR), 1.5; 95% confidence interval (95% CI), 1.2-2.0 and OR, 1.9; 95% CI, 1.4-2.5] to seek screening compared with those without a family history or worry. The association between family history and frequent screening was similar in men who were married or living with someone (OR, 1.7; 95% CI, 1.2-2.2); however, it was reduced among men who live alone (OR, 0.6; 95% CI, 0.2-1.8). These data suggest that psychosocial factors such as family history, worry, or concern about prostate cancer and marital status may play an important role in men's decisions about prostate cancer screening. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3588–92)

Abstract Allergen-induced respiratory inflammation facilitates and/or elicits the extravasation of proinflammatory leukocytes by well-understood mechanisms that mediate the movement of multiple cell types. The nonspecific character of these pathways led us to hypothesize that circulating cancer cells use similar mechanisms, promoting secondary tumor formation at distal sites. To test this hypothesis, the frequency of metastasis to the lung as a function of allergic pulmonary inflammation was assessed following the i.v. injection of B16-F10 melanoma cells in mice. These studies showed that allergen-induced pulmonary inflammation resulted in a &gt;3-fold increase in lung metastases. This increase was dependent on CD4+ T-cell activities; however, it occurred independent of the induced eosinophilia associated with allergen provocation. Interventional strategies showed that existing therapeutic modalities for asthma, such as inhaled corticosteroids, were sufficient to block the enhanced pulmonary recruitment of cancer cells from circulation. Additional mechanistic studies further suggested that the ability of circulating cancer cells to extravasate to surrounding lung tissues was linked to the activation of the vascular endothelium via one or more Gαi-coupled receptors. Interestingly, a survey of a clinical breast cancer surgical database showed that the incidence of asthma was higher among patients with lung metastases. Thus, our data show that allergic respiratory inflammation may represent a risk factor for the development of lung metastases and suggest that amelioration of the pulmonary inflammation associated with asthma will have a direct and immediate benefit to the 7% to 8% of breast cancer patients with this lung disease. [Cancer Res 2008;68(20):8582–9]

ABSTRACT Introduction Testosterone replacement therapy has been used in the treatment of sexual dysfunction; however, its use remains controversial, and the effectiveness and long-term health implications are unknown. Aim To evaluate the association between sex hormone serum levels, erectile function, and sexual drive in a population-based sample of men. Methods A stratified random sample of men residing in Olmsted County, Minnesota, completed a questionnaire containing questions from the Brief Male Sexual Function Inventory (BMSFI), and participated in a clinical exam, which included serum hormone measurements. Main Outcome Measures Levels of sexual drive (libido) and erectile function as assessed by the BMSFI and serum testosterone, bioavailable testosterone, and estradiol measurements. Results Out of 414 men, 294 had a regular sexual partner and androgen measurements at the 14th year of follow-up. Total testosterone and erectile function were significantly correlated even after adjustment for age (r = 0.12, P = 0.04). Conversely, total testosterone was not significantly correlated with sex drive (r = 0.08, P = 0.17). Bioavailable testosterone was significantly correlated with both erectile function and sex drive (r = 0.16, P = 0.01 and r = 0.20, P = 0.001, respectively). However, these associations disappeared after age adjustment (r = 0.04 and r = 0.09). Conclusions These cross-sectional results suggest the relationship between sex hormones and sexual function is complex, and that the age-related decline in sexual function may be due to age-related declines in levels of bioavailable testosterone rather than total testosterone levels.

Abstract Aim: To examine the use of complementary and alternative medicine (CAM) by women with varying levels of familial and perceived risk of breast cancer with the goal of preventing breast cancer. Methods: Cross-sectional data on CAM use were collected on 2,198 women (mean age, 63 years) personally unaffected by breast cancer in the Minnesota Breast Cancer Family Study. CAM use was compared across women at high, moderate, or average risk based on family history, as well as across categories of perceived risk of breast cancer. CAM use was also examined in relation to screening and general health behaviors, worry about breast cancer, and optimism. Results: Half (49.5%) of the women reported using at least one CAM modality with the intent of preventing breast cancer. Univariate analyses indicated that greater overall CAM use was related to greater perceived risk (P = 0.018), more general health behaviors (P &lt; 0.0001), more breast cancer screening behaviors (P = 0.0002), greater optimism (P = 0.0002), and higher educational attainment (P &lt; 0.0001). Multivariate analysis revealed that general health behaviors (P &lt; 0.0001), education (P = 0.0027), and optimism (P = 0.037) were significant predictors of CAM use when in the same model with perceived risk and breast cancer screening behaviors. Conclusions: Many women use CAM with the goal of preventing breast cancer. General health-promoting behaviors, education, and optimism predict CAM use. Evidence-based guidance is needed for the public and health care providers on the potential and limitations of specific CAM approaches to affect cancer risk. (Cancer Epidemiol Biomarkers Prev 2008;17(6):1527–34)

ABSTRACT Introduction Severe obstructive sleep apnea has been associated with sexual dysfunction; however, it is unclear whether milder forms of sleep disturbances might also be associated with sexual problems. Aim To evaluate the association between snoring and five measures of sexual dysfunction in a population-based sample of men. Methods A stratified random sample of men residing in Olmsted County, Minnesota completed a questionnaire containing questions from the Brief Male Sexual Function Inventory (BMSFI) and a sleep questionnaire. Main Outcome Measures Levels of sexual drive (libido), erectile function, ejaculatory function, sexual problem assessment, and sexual satisfaction as assessed by the BMSFI. Results Of 827 men with a regular sexual partner, subjects were divided into categories of heavy (N=95), moderate (N=573), and none/mild (N=159) snoring. Their median age was 64 years (range 51–90). The sexual satisfaction domain score was significantly lower in the heavy snoring group (P value=0.01). The odds of low sexual satisfaction was 2.3 (95% CI 1.2, 4.1) among the heavy snorers compared with the none/mild snoring group. This association remained statistically significant after adjustment for smoking, medical comorbidities, and mental health status. However, there was no significant difference in ejaculatory function, erectile function, sexual drive, and sexual problem assessment across snoring categories. Conclusions These data provide evidence of an association between snoring severity and reduced sexual satisfaction in a population of elderly community males. Snoring was not associated with biologic measures of sexual dysfunction.

The current paradigm surrounding allergen-mediated T helper type 2 (Th2) immune responses in the lung suggests an almost hegemonic role for T cells. Our studies propose an alternative hypothesis implicating eosinophils in the regulation of pulmonary T cell responses. In particular, ovalbumin (OVA)-sensitized/challenged mice devoid of eosinophils (the transgenic line PHIL) have reduced airway levels of Th2 cytokines relative to the OVA-treated wild type that correlated with a reduced ability to recruit effector T cells to the lung. Adoptive transfer of Th2-polarized OVA-specific transgenic T cells (OT-II) alone into OVA-challenged PHIL recipient mice failed to restore Th2 cytokines, airway histopathologies, and, most importantly, the recruitment of pulmonary effector T cells. In contrast, the combined transfer of OT-II cells and eosinophils into PHIL mice resulted in the accumulation of effector T cells and a concomitant increase in both airway Th2 immune responses and histopathologies. Moreover, we show that eosinophils elicit the expression of the Th2 chemokines thymus- and activation-regulated chemokine/CCL17 and macrophage-derived chemokine/CCL22 in the lung after allergen challenge, and blockade of these chemokines inhibited the recruitment of effector T cells. In summary, the data suggest that pulmonary eosinophils are required for the localized recruitment of effector T cells.

OBJECTIVE—The aim of this study was to examine associations between diabetes and clinical markers of benign prostatic hyperplasia (BPH) in community-dwelling white and black men aged 40–79 years. RESEARCH DESIGN AND METHODS—Data from the Olmsted County Study of Urinary Symptoms and Health Status and the Flint Men's Health Study were combined for a total study sample of 2,484 men. Severity of lower urinary tract symptoms (LUTS), peak urinary flow rates, prostate volume, and serum prostate-specific antigen (PSA) levels were examined by self-reported physician-diagnosed diabetes. RESULTS—Overall, 170 men (6.8%) reported a history of diabetes. Increased irritative LUTS and specifically nocturia were positively associated with diabetes. These patterns were consistent across race and persisted after adjustment for age, BMI, and various indicators of socioeconomic status. Furthermore, the relationship between irritative LUTS and diabetes was greater in black men. No significant associations were observed between diabetes and prostate volume, PSA level, and peak urinary flow rate. CONCLUSIONS—Our multiethnic community-based study demonstrates positive associations between diabetes and irritative LUTS and nocturia. Moreover, the association between irritative LUTS and diabetes is increased in black men. There was no strong evidence for an association between diabetes and BPH across measures more specific to BPH (i.e., prostate volume, PSA, and peak urinary flow rate). Taken together, our findings suggest that the presence of diabetes may be less related to prostate growth and more related to the dynamic components of lower urinary tract function. Further evaluations of the association between diabetes and BPH and related racial variations are warranted.