Efficacy of primary hormonal therapy for patients with localized and locally advanced prostate cancer: A retrospective multicenter study

AIM: A retrospective review of patients with localized and locally advanced prostate cancer was performed to evaluate the efficacy of primary hormonal therapy and predict long-term prognosis in these patients. METHODS: A total of 628 patients who were diagnosed with stage T1c to T3 prostate cancer were treated with primary hormonal therapy at participating institutions. The patients were classified based on pretreatment prostate-specific antigen (PSA) level, Gleason score, and time to nadir PSA level. Disease-specific and progression-free survival rates were investigated, and compared among the subgroups. RESULTS: The mean age of patients was 74.5 years, and median pretreatment PSA level was 14.0 ng/mL. A total of 399 patients (63.5%) were treated with combined androgen blockade (CAB), and 229 patients (36.5%) were treated with castration monotherapy. The disease-specific survival rate of all 628 patients was 89.1% at 8 years. The group that showed a good response to primary hormonal therapy (Group G, pretreatment PSA level < or =20 ng/mL, Gleason score < or =7, and time to nadir PSA < or =6 months) accounted for approximately one-third of the total number of T1c-T3 patients. Disease-specific and progression-free survival rates at 8 years in Group G were 98.9% and 82.0%, respectively. These rates increased to 100% and 87.3%, respectively, in patients receiving CAB treatment in Group G. CONCLUSIONS: The results indicate the usefulness of primary hormonal therapy, especially CAB treatment, for patients showing a good response to hormonal therapy in long-term control of localized and locally advanced prostate cancer.     

Inhibition of monosodium urate monohydrate crystal-induced acute inflammation by retrovirally transfected prostaglandin D synthase

OBJECTIVE: Hematopoietic prostaglandin D synthase (H-PGDS) is a key enzyme in the production of prostaglandin D and its J series metabolites. We evaluated the antiinflammatory effect of retrovirally transfected H-PGDS in order to investigate the role of H-PGDS in monosodium urate monohydrate (MSU) crystal-induced acute inflammation. METHODS: Expression of endogenous PGDS in a murine air-pouch model of MSU crystal-induced acute inflammation was determined by real-time polymerase chain reaction. H-PGDS complementary DNA (cDNA) was retrovirally transfected into C57BL/6J fibroblasts, and the cells were designated as C57-PGDS cells. Production of prostaglandins by C57-PGDS cells was measured by enzyme immunoassay. The effect of C57-PGDS cells on crystal-induced inflammation was investigated. RESULTS: Injection of the crystals caused a rapid decrease in H-PGDS expression by infiltrating cells and by the soft tissues around the air pouches. In contrast, expression of interleukin-1beta (IL-1beta) and macrophage inflammatory protein 2 (MIP-2) as well as cellular infiltration were significantly increased during the early stage of inflammation. C57-PGDS cells, but not control cells, produced an increased amount of PGD(2) in vitro, but suppressed production of PGE(2). Injection of C57-PGDS cells into air pouches inhibited cellular infiltration and MIP-2 and IL-1beta expression. CONCLUSION: In this murine air-pouch model of MSU crystal-induced inflammation, retrovirally transfected H-PGDS cDNA could reduce cellular infiltration, at least partly by inhibiting MIP-2 and IL-1beta. These findings suggest that gene therapy with H-PGDS may be useful for treating inflammatory diseases.     

Psychological distress and the perception of radiation risks: the Fukushima health management survey

Objective

To assess relationships between the perception of radiation risks and psychological distress among evacuees from the Fukushima nuclear power plant disaster.

Methods

We analysed cross-sectional data from a survey of evacuees conducted in 2012. Psychological distress was classified as present or absent based on the K6 scale. Respondents recorded their views about the health risks of exposure to ionizing radiation, including immediate, delayed and genetic (inherited) health effects, on a four-point Likert scale. We examined associations between psychological distress and risk perception in logistic regression models. Age, gender, educational attainment, history of mental illness and the consequences of the disaster for employment and living conditions were potential confounders.

Findings

Out of the 180 604 people who received the questionnaire, we included 59 807 responses in our sample. There were 8717 respondents reporting psychological distress. Respondents who believed that radiation exposure was very likely to cause health effects were significantly more likely to be psychologically distressed than other respondents: odds ratio (OR) 1.64 (99.9% confidence interval, CI: 1.42–1.89) for immediate effects; OR: 1.48 (99.9% CI: 1.32–1.67) for delayed effects and OR: 2.17 (99.9% CI: 1.94–2.42) for genetic (inherited) effects. Similar results were obtained after controlling for individual characteristics and disaster-related stressors.

Conclusion

Among evacuees of the Fukushima nuclear disaster, concern about radiation risks was associated with psychological distress.     

Insulin receptor isolation studies

The observation that N^α,B1-biotinylinsulin binds firmly to resins in which succinoylavidin is covalently attached to AH Sepharose 4B and can be retrived by exposure of the resins to 20 mM biotin provided the basis for the present investigations. Solubilized, partially purified insulin receptor from human placenta binds to affinity resins in which N^α,B1-biotinylinsulin is noncovalently attached to AH Sepharose 4B-immobilized-succinoylavidin. Exposure of the receptor loaded resin to 20 mM biotin results in liberation of a high molecular weight material containing bound ¹²⁵I-biotinylinsulin, which precipitates with polyethyleneglycol and cross reacts with human insulin receptor antibodies. The technique is biospecific and appears to be applicable to the purification of insulin receptors on a preparative scale. Crude solubilized insulin receptor from human placenta is contaminated with “insulinase” which is inhibited by N-ethylmaleimide. HPLC provides a tool to assess “insulinase” activity that is more sensitive than the TCA precipitation method.     

Electrically stimulated ventilation feedback improves the ventilation pattern in patients with COPD

[Purpose] We aimed to determine the effects of ventilation feedback using electrical stimulation on ventilation pattern during exercise in patients with chronic obstructive pulmonary disease (COPD), and develop new rehabilitation methods. [Subjects] This randomized double-blind placebo-controlled trial included 24 patients with COPD. [Methods] Phasic electrical stimulation during expiration (PESE) or a placebo was given to all the cases. Minute ventilation (VE), tidal volume (TV), respiratory rate (RR), expiratory time (Te), total respiratory time (Ttot), dead-space gas volume to tidal gas volume (VD/VT), oxygen uptake (VO₂), carbon dioxide output (VCO₂), Borg scale (Borg), and percutaneous oxygen saturation (SpO₂) during rest and exercise were assessed. [Results] The placebo group showed no obvious change in ventilation measurements at rest or during exercise. However, in the PESE group, TV, Te, and Ttot significantly increased, while RR and VD/VT significantly decreased during exercise compared with the baseline measurements. Borg scores, SpO₂, VO₂, or VCO₂ did not differ significantly. [Conclusion] PESE improves the ventilation pattern during rest and exercise. Furthermore, PESE does not increase VO₂, which may indicate an increased workload. Biofeedback may contribute to PESE effects. Stimulation applied during expiration may evoke sensations increasing prolonged expiration awareness, facilitating prolongation.Key words: Chronic obstructive pulmonary disease, Electrical stimulation, Ventilation     

Immunogenetic features in 120 Japanese patients with idiopathic inflammatory myopathy

OBJECTIVE: To examine the role of HLA-DRB1 and tumor necrosis factor (TNF) promoter genotypes in the development and the autoantibody profiles of idiopathic inflammatory myopathy (IIM) in Japanese patients. METHODS: HLA-DRB1 and TNF promoter genotypes were determined, and serum antinuclear autoantibodies were identified in 120 adult Japanese patients with IIM [72 with dermatomyositis (DM), 30 with polymyositis (PM), 18 with myositis overlapping with other collagen vascular diseases], as well as in 265 controls. RESULTS: Forty-two patients (35%) were positive for myositis-specific autoantibodies (MSA), including 37 (31%) for anti-aminoacyl-tRNA synthetase (ARS) autoantibodies. Allele carrier frequency of HLA-DRB1*0803 was increased in the patients with IIM [p = 0.02, corrected p (pc) NS, 23% vs 14%, odds ratio (OR) = 1.9 (95% confidence interval, CI = 1.1-3.2)], with PM [p = 0.006, pc NS, 33%, OR 3.1 (95% CI 1.3-7.1)], and with anti-ARS autoantibodies [27%, p = 0.04, OR 2.3 (95% CI 1.0-5.1)] compared with controls. DRB1*0405 was increased in patients with anti-ARS autoantibodies compared with controls [41% vs 25%, p = 0.04, pc NS, OR 2.1 (95% CI 1.0-4.3)]. TNF promoter genotype was associated with the presence of interstitial lung disease (ILD). The carriage of a TNF-a haplotype formed by -1031C, -863A, and -857C was increased in the patients with ILD versus those without ILD [33% vs 18%, p = 0.05, pc NS, OR 2.3 (95% CI 0.94-5.5)]. CONCLUSION: HLA-DRB1 alleles were associated with development of IIM and MSA in a Japanese population.