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Hansen TK Fisker S Hansen B Sørensen HH Christiansen JS Jørgensen JO ØRskov H 《Clinical endocrinology》2002,56(6):779-786
BACKGROUND: Prostate cancer (PCa) is one of the most common cancers in men and has an increasing incidence. In 1999, 37 000 men died from PCa in the USA. Androgen deprivation therapy (ADT) with GnRH agonists is frequently employed in the treatment of recurrent and metastatic PCa by inducing medical castration, rendering these men hypogonadal. Because hypogonadism in men is associated with a wide range of complications, we attempted to determine the effects of long-term ADT in men with PCa. METHODS: We conducted a cross-sectional study at a tertiary care centre to determine the effect of ADT on lean body mass (LBM), muscle strength, bone mineral density (BMD), sexual function, and quality of life (QOL) in men with PCa. Three groups of men were enrolled: (1) 20 men with PCa who were undergoing medical castration with GnRH agonists for at least 12 months prior to the onset of the study (ADT group); (2) 18 age-matched men with nonmetastatic PCa who were post prostatectomy and/or radiotherapy but had not yet undergone ADT (non-ADT group); and (3) 20 age-matched normal men who were healthy and ambulatory (control group). RESULTS: Men on ADT had castrate levels of serum total testosterone (P < 0.0001), free testosterone (P < 0.0001) and oestradiol (P < 0.0001), which were significantly lower than in the other groups. Total body (P = 0.03) and lumbar spine (P < 0.0001) BMD was significantly lower in patients on ADT compared to other groups and was associated with higher levels of urinary N-telopeptide (P = 0.02). The ADT group had higher fat mass compared to the other groups (P = 0.0001) and significantly reduced upper body strength (P = 0.001) when compared to non-ADT patients. The ADT group had lower overall scores on Watt's Sexual Function Questionnaire compared to other groups (P = 0.0001), in particular a decrease in desire, arousal and frequency of spontaneous early morning erections. The ADT group also had lower overall QOL scores, resulting in significant limitation of physical function (P = 0.001), role limitation (P = 0.02) and perception of physical health (P = 0.004). CONCLUSIONS: This study suggests that osteoporosis, unfavourable body composition, sexual dysfunction and reduced quality of life are seen in patients receiving androgen deprivation therapy for at least 12 months. Longitudinal studies in this patient population will shed further light on the timing of the development and the extent of these complications. Meanwhile, this information will assist both physicians and patients with prostate cancer to make informed decisions regarding androgen deprivation therapy. 相似文献
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Matthew A. Cavender Anna Norhammar Kåre I. Birkeland Marit Eika Jørgensen John P. Wilding Kamlesh Khunti Alex Z. Fu Johan Bodegård Betina T. Blak Eric Wittbrodt Marcus Thuresson Peter Fenici Niklas Hammar Mikhail Kosiborod 《Journal of the American College of Cardiology》2018,71(22):2497-2506
Background
Prior studies found patients treated with sodium-glucose co-transporter-2 inhibitors (SGLT-2i) had lower rates of death and heart failure (HF). Whether the benefits of SGLT-2i vary based upon the presence of cardiovascular disease (CVD) is unknown.Objectives
This study sought to determine the association between initiation of SGLT-2i therapy and HF or death in patients with and without CVD.Methods
The CVD-REAL (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors) study was a multinational, observational study in which adults with type 2 diabetes were identified. Patients prescribed an SGLT-2i or other glucose-lowering drugs (GLDs) were matched based on a propensity score for initiation of an SGLT-2i. Hazard ratios (HRs) for the risk of death, HF, and HF or death in patients with and without established CVD were estimated for each country and pooled.Results
After propensity score matching, 153,078 patients were included in each group. At baseline, 13% had established CVD. Compared with therapy using other GLDs, initiation of an SGLT-2i was associated with lower risk of death in patients with and without CVD (HR: 0.56; 95% confidence interval [CI]: 0.44 to 0.70; and HR: 0.56; 95% CI: 0.50 to 0.63, respectively). There were also associations between SGLT-2i and lower risk of HF (HR: 0.72; 95% CI: 0.63 to 0.82; and HR: 0.61; 95% CI: 0.48 to 0.78, respectively) and the composite of HF or death (HR: 0.63; 95% CI: 0.57 to 0.70; and HR: 0.56; 95% CI: 0.50 to 0.62, respectively) observed in patients with and without established CVD.Conclusions
In this large, multinational, observational study, initiation of SGLT-2i was associated with lower risk of death and HF regardless of pre-existing CVD. Ongoing clinical trials will provide further evidence regarding the benefit of SGLT-2i in patients without established CVD. (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors [CVD-REAL]; NCT02993614) 相似文献64.
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Quantitative real-time polymerase chain reaction (qPCR) has become a widely used tool in the search for disease genes. When examining gene expression with qPCR in psychiatric diseases, endogenous reference gene(s) must be used for normalization. Traditionally, genes such as beta-actin (ActB), Gapd, and 18s rRNA, assumed to be stably expressed, have been used for normalization. However, it has become clear that expression of these genes is influenced by different experimental paradigms. Since stable gene expression of houskeeping genes (HKGs), therefore, cannot be expected, alternative strategies are warranted. With the overall aim to inspect the gene expression of three target genes, NMDAR1, SORT, and CREB, in rat hippocampus, we tested a panel of eight HKGs, 18s rRNA, ActB, CycA, Gapd, Hmbs, Hprt1, Rpl13A, and Ywhaz in order to select the most stably expressed gene, using the NormFinder and geNorm software applets. Additionally, we have applied four different normalization approaches for normalization of the three target genes. We found using the NormFinder software that Ywhaz is the most stably expressed gene among the eight tested HKGs. However, the results of the analysis of the target genes are highly dependent on the choice of normalization approach. Moreover, the number of HKGs, used for selection of the most stable HKG, also influences on the result of the gene expression analysis of target genes. These results underline the importance of choosing a proper normalization strategy when analyzing gene expression with qPCR. The strategy should be unbiased and carried out in every specific experimental setting. 相似文献
68.
Golub JE Saraceni V Cavalcante SC Pacheco AG Moulton LH King BS Efron A Moore RD Chaisson RE Durovni B 《AIDS (London, England)》2007,21(11):1441-1448
BACKGROUND: Tuberculosis is a common complication and leading cause of death in HIV infection. Antiretroviral therapy (ART) lowers the risk of tuberculosis, but may not be sufficient to control HIV-related tuberculosis. Isoniazid preventive therapy (IPT) reduces tuberculosis incidence significantly, but is not widely used. METHODS: We analysed tuberculosis incidence in 11 026 HIV-infected patients receiving medical care at 29 public clinics in Rio de Janeiro, Brazil, between 1 September 2003 and 1 September 2005. Data were collected through a retrospective medical record review. We determined rates of tuberculosis in patients who received neither ART nor IPT, only ART, only IPT, or both ART and IPT. RESULTS: The overall tuberculosis incidence was 2.28 cases/100 person-years (PY) [95% confidence interval (CI) 2.06-2.52]. Among patients who received neither ART nor IPT, incidence was 4.01/100 PY. Patients who received ART had an incidence of 1.90/100 PY (95% CI 1.66-2.17) and those treated with IPT had a rate of 1.27/100 PY (95% CI 0.41-2.95). The incidence among patients who received ART and IPT was 0.80/100 PY (95% CI 0.38-1.47). Multivariate Cox proportional hazards modeling revealed a 76% reduction in tuberculosis risk among patients receiving both ART and IPT (adjusted relative hazard 0.24; P < 0.001) after adjusting for age, previous tuberculosis diagnosis, and CD4 cell counts at baseline. CONCLUSION: The use of both IPT and ART in HIV-infected patients is associated with significantly reduced tuberculosis incidence. In conjunction with expanded access to ART, the wider use of IPT in patients with HIV will improve tuberculosis control in high burden areas. 相似文献
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