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991.
M. R. Müller K. Lennartz C. Boogen M. R. Nowrousian M. F. Rajewsky S. Seeber 《Annals of hematology》1992,65(5):206-212
Summary A 4-day colorimetric tetrazolium dye (MTT) assay was used to assess the cytotoxicity of adriamycin (ADM), vincristine (VCR), and idarubicin (IDA) in blasts isolated from 37 patients with newly diagnosed and pretreated acute myeloid leukemia (AML). The effect of verapamil (VRP) as a chemosensitizer was studied in relation to the expression of the membrane efflux pump P-glycoprotein (PGP) as determined by a semiquantitative flow-cytometric procedure. A slight positive correlation was found between the fraction of cells expressing PGP and the ID50 values for ADM and VCR, but not between cellular PGP content and sensitivity to IDA. The overall data showed no significant sensitization effect of VRP. However, in specimens with more than 10% cells expressing PGP, 2M VRP sensitized cells to ADM and VCR significantly. The median of sensitization ratios (SRs), i.e., the ratios of cytotoxic drug ID50 in the absence/presence of VRP, were 1.89 and 2.0, respectively. No sensitizing effect of VRP on the cytotoxicity of IDA was observed. Related to the clinical status, the median fraction of PGP-positive blasts was elevated fourfold in pretreated patients (n=16) in comparison to patients with de novo AML (n=19). No differences in ID50 values were observed between newly diagnosed and pretreated patients. However, SRs for ADM and VCR were higher in samples of pretreated patients compared with de novo AML. PGP-mediated cellular drug resistance may thus be circumvented in leukemic blasts by application of chemosensitizers or, potentially, alternative anthracyclines. 相似文献
992.
James L. Januzzi Annabel A. Chen-Tournoux Robert H. Christenson Gheorghe Doros Judd E. Hollander Phillip D. Levy John T. Nagurney Richard M. Nowak Peter S. Pang Darshita Patel W. Franklin Peacock E. Joy Rivers Elizabeth L. Walters Hanna K. Gaggin 《Journal of the American College of Cardiology》2018,71(11):1191-1200
Background
Contemporary reconsideration of diagnostic N-terminal pro–B-type natriuretic peptide (NT-proBNP) cutoffs for diagnosis of heart failure (HF) is needed.Objectives
This study sought to evaluate the diagnostic performance of NT-proBNP for acute HF in patients with dyspnea in the emergency department (ED) setting.Methods
Dyspneic patients presenting to 19 EDs in North America were enrolled and had blood drawn for subsequent NT-proBNP measurement. Primary endpoints were positive predictive values of age-stratified cutoffs (450, 900, and 1,800 pg/ml) for diagnosis of acute HF and negative predictive value of the rule-out cutoff to exclude acute HF. Secondary endpoints included sensitivity, specificity, and positive (+) and negative (?) likelihood ratios (LRs) for acute HF.Results
Of 1,461 subjects, 277 (19%) were adjudicated as having acute HF. The area under the receiver-operating characteristic curve for diagnosis of acute HF was 0.91 (95% confidence interval [CI]: 0.90 to 0.93; p < 0.001). Sensitivity for age stratified cutoffs of 450, 900, and 1,800 pg/ml was 85.7%, 79.3%, and 75.9%, respectively; specificity was 93.9%, 84.0%, and 75.0%, respectively. Positive predictive values were 53.6%, 58.4%, and 62.0%, respectively. Overall LR+ across age-dependent cutoffs was 5.99 (95% CI: 5.05 to 6.93); individual LR+ for age-dependent cutoffs was 14.08, 4.95, and 3.03, respectively. The sensitivity and negative predictive value for the rule-out cutoff of 300 pg/ml were 93.9% and 98.0%, respectively; LR? was 0.09 (95% CI: 0.05 to 0.13).Conclusions
In acutely dyspneic patients seen in the ED setting, age-stratified NT-proBNP cutpoints may aid in the diagnosis of acute HF. An NT-proBNP <300 pg/ml strongly excludes the presence of acute HF. 相似文献993.
Amit Kumar Sharma Neeraj Gupta Dilip Kumar Kala Tarun Patni Ramakant Dixit Satyadeep Verma Arjun Chandran 《The Indian journal of tuberculosis》2018,65(3):233-236
Aims and objectives
To determine the prevalence and pattern of resistance to second line drugs among multi drug resistant (MDR) tuberculosis patients being treated on category IV regimen.Methodology
This study was conducted at Department of Respiratory Medicine, J.L.N. Medical College, Ajmer in collaboration with IRL, STDC, Ajmer. Second line anti tubercular drug sensitivity for 398 multi drug resistant tuberculosis patients (between June-2015 and June-2016) was done to find out prevalence and pattern of resistance to second line drugs. Second line drug sensitivity was performed at accredited laboratory, Microbiology department, S.M.S. Medical College, Jaipur.Results
Among these 398 patients, 136 (34.17%) were resistant to fluoroquinolones (Ofloxacin) (Pre XDR); 18 (4.52%) were resistant to one of the aminoglycosides (Inj. Kanamycin, Capreomycin, Amikacin) (Pre XDR); while 22 (5.53%) patients were resistant to fluoroquinolones as well as aminoglycosides (XDR). 148 (37.18%) patients were found sensitive to both the drugs. Samples of 41 (10.3%) patients were contaminated and no growth was seen in 33 (8.29%) patients.Conclusion
Nearly half of the multi drug resistant (MDR) tuberculosis patients (44.22%) being treated on category IV regimen also have resistance to either fluoroquinolones or aminoglycosides or both i.e. Pre XDR or XDR. This may result in poor outcome of category IV regimen under RNTCP. There is a strong need for provision of culture sensitivity for all first line drugs and at least two second line drugs viz. Fluoroquinolones and aminoglycosides for all the patients registered as smear positive under RNTCP. There is also a need for development of rapid culture technique for sensitivity to second line drugs. 相似文献994.
目的评价吉西他滨联合顺铂(GP方案)治疗老年晚期非小细胞肺癌的临床疗效与毒副反应。方法对30例经病理和(或)细胞确诊的老年晚期非小细胞肺癌患者,采用吉西他滨联合顺铂化疗。吉西他滨1000mg/m^2,静脉点滴,第1,8天各静滴1次;顺铂25mgc/m^2,静脉点滴,第1,2,3天各静滴1次,每28d为一个周期,化疗中记录毒副反应。2个周期为1个疗程。疗程结束后,评定疗效与毒副反应。结果全组完全缓解(CR)0例,部分缓解11例(11/30),总有效率36.67%。最常见的毒副反应为白细胞减少和血小板减少。结论吉西他滨联合顺铂方案治疗老年晚期非小细胞肺癌患者临床疗效较好,毒副反应可耐受,值得推广应用。 相似文献
995.
The anti-inflammatory effect on contact dermatitis of the water solubilized 1′-Acetoxychavicol Acetate (ACA) by complexation with β-1,3-glucan isolated form Aureobasidium pullulans black yeast is reported. It is well-known that ACA possesses a function to inhibit the activation of NF-κB by which genes encoding proinflammatory cytokines, chemokines, and growth factors are regulated. However, because ACA is quite insoluble in water, its usefulness has been extremely limited. On the other hand, a triple-helical polysaccharide β-1,3-glucan can include hydrophobic compounds into intrastrand hydrophobic cavity and solubilize poorly water-soluble compounds. In this study, solubilization of ACA by complexation with highly branched β-1,3-glucan was achieved. The effect of anti-inflammatory response of water-soluble ACA complex with β-1,3-glucan was confirmed in vitro and in vivo. 相似文献
996.
Pathologic angiogenesis induced by hypoxia is a hallmark of ischemic retinopathy including diabetic retinopathy and retinopathy of prematurity. These 2 diseases affect substantial number of working population and preterm babies, respectively, resulting in visual deterioration. It is essential for novel therapeutics for ischemic retinopathy to demonstrate the potency in reducing pathologic angiogenesis and the safety without definite toxicity on the retina and the whole body. In this review, we suggest a novel platform of integrative studies from in vitro to in vivo experiments on angiogenesis and toxicity with the aim of accelerating and facilitating the development of novel therapeutic agents for ischemic retinopathy. Robust in vitro and in vivo studies with bridging microfluidic and ex vivo systems help researchers to evaluate the efficacy and anticipate the toxicity of candidate drugs. We hope that novel therapeutic approach based on this platform will be developed in near future and reduce the incidence of vision loss from ischemic retinopathy. 相似文献
997.
朱婉秋 《国际输血及血液学杂志》2015,38(2)
免疫球蛋白轻链型淀粉样变性(AL)是最为常见的淀粉样变性类型.近年,AL型淀粉样变性的治疗已取得一定进展.笔者拟就AL型淀粉样变性治疗的相关研究进展,包括基于自体造血干细胞移植治疗方案、基于美法仑治疗方案、基于蛋白酶体抑制剂治疗方案、基于免疫调节剂治疗方案及免疫治疗方案进行综述. 相似文献
998.
Ming-Chao Li Zheng-Yun Wang Jun Yang Xiao-Lin Guo Tao Wang Shao-Gang Wang Ji-Hong Liu Zhang-Qun Ye 《Asian journal of andrology》2015,17(1):124-134
We performed a meta-analysis to compare treatment with a combination of solifenacin plus tamsulosin oral controlled absorption system (TOCAS) with placebo or TOCAS monotherapy. The aim of the meta-analysis was to clarify the efficacy and safety of the combination treatments method for lower urinary tract symptoms (LUTS). We searched for trials of men with LUTS that were randomized to combination treatment compared with TOCAS monotherapy or placebo. We pooled data from three placebo-controlled trials meeting inclusion criteria. Primary outcomes of interest included changes in International Prostate Symptom Score (IPSS) and urinary frequency. We also assessed postvoid residual, maximum urinary flow rate, incidence of urinary retention (UR), adverse events. Data were pooled using random or fixed effect models for continuous outcomes and the Mantel–Haenszel method to generate risk ratio. Reductions in IPSS storage subscore and total urgency and frequency score (TUFS) were observed with solifenacin 6 mg plus TOCAS compared with placebo (P < 0.0001 and P < 0.0001, respectively). Reductions in IPSS storage subscore and TUFS were observed with solifenacin 9 mg plus TOCAS compared with placebo (P = 0.003 and P = 0.0006, respectively). Reductions in TUFS was observed with solifenacin 6 mg plus TOCAS compared with TOCAS (P = 0.01). Both combination treatments were well tolerated, with low incidence of UR. Solifenacin 6 mg plus TOCAS significantly improved total IPSS, storage and voiding symptoms compared with placebo. Solifenacin 6 mg plus TOCAS also improved storage symptoms compared with TOCAS alone. There was no additional benefit of solifenacin 9 mg compared with 6 mg when used in combination with TOCAS. 相似文献
999.
1000.
《Urologic oncology》2015,33(7):310-321
Prostate cancer (PCa) is a hormone-sensitive disease. Androgen deprivation therapy lowers serum testosterone levels (castration) or blocks the androgen receptor (AR) ligand-binding domain. Especially in metastatic disease, hormonal therapy has been able to delay disease progression, reduce symptoms, and improve overall survival. Despite subsequent disease progression and development of castration resistance, PCa remains AR driven. Secondary hormonal treatments such as abiraterone acetate or enzalutamide have demonstrated increased overall survival. However, new resistance mechanisms to these agents have been identified, and systemic chemotherapy is still needed especially in fast-progressing castration-resistant PCa. Several promising androgen synthesis inhibitors (orteronel and galeterone), AR inhibitors (ARN-509, EPI-001, AZD3514, and ODM-201), and heat shock protein modulators (AT11387, 17-DMAG, STA-9090, and OGX-427) are currently under investigation. The wide variety in upcoming systemic agents underlines the molecular heterogeneity of castration-resistant PCa. This article reviews antihormonal therapy in PCa and resistance mechanisms and focuses on novel and upcoming agents currently in clinical testing. 相似文献