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61.
Melissa Soohoo Elani Streja Yoshitsugu Obi Connie M. Rhee Daniel L. Gillen Keiichi Sumida Danh V. Nguyen Csaba P. Kovesdy Kamyar Kalantar-Zadeh 《Mayo Clinic proceedings. Mayo Clinic》2018,93(8):1074-1085
Objective
To determine whether kidney function level and its rate of decline in the immediate predialysis period among veterans transitioning to end-stage renal disease (ESRD) predict postdialysis mortality and hospitalization.Patients and Methods
In 19,985 veterans transitioning to ESRD during the period October 1, 2007, to March 30, 2014, we examined kidney function and its slope over the final year of the pre-ESRD(prelude) period. Two categories of low vs high estimated glomerular filtration rate (eGFR, dichotomized at 10 mL/min/1.73 m2) and slow vs fast slope (dichotomized at ?10 mL/min/1.73 m2/y) were combined into 4 groups. Their associations with 12-month post-ESRD all-cause and cardiovascular (CV) mortality and hospitalization rates were examined in adjusted models accounting for clinical characteristics and laboratory measurements at transition.Results
Patients, 66±11 years old, and 34% blacks, had a median (interquartile range) eGFR at transition and slope of 9.7 (7.1-13.3) mL/min/1.73 m2 and ?10.5 (?18.8 to ?5.9) mL/min/1.73 m2/y, respectively. Patients with a low eGFR and slow slope had the lowest 12-month all-cause and CV mortality risks and hospitalization rate. Conversely, patients with high eGFR and fast slope had the highest risk of all-cause and CV mortality and hospitalization rate compared with patients with a low eGFR and slow slope. This relationship persisted in sensitivity analyses, including propensity scoring.Conclusion
A kidney profile of a low eGFR and slow slope in the prelude period is associated with favorable early dialysis outcomes in veteran patients. Trials to examine a more conservative approach to dialysis are warranted. 相似文献62.
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66.
Effects of medroxyprogesterone and estradiol on the recovery of spermatogenesis in irradiated rats 总被引:1,自引:0,他引:1
Shetty G Weng CC Bolden-Tiller OU Huhtaniemi I Handelsman DJ Meistrich ML 《Endocrinology》2004,145(10):4461-4469
Suppression of intratesticular testosterone (ITT) levels is required for spermatogenic recovery in rats after irradiation, but maintenance of peripheral testosterone (T) levels is important for many male functions. Considering the preservation of peripheral T while suppressing ITT, we tested the effects of a combination of a progestin, medroxyprogesterone acetate (MPA), plus T on spermatogenic recovery after irradiation, and compared its effects to those of T alone or T combined with estradiol (E2). Rats were given testicular irradiation (6 Gy) and treated during wk 3-7 after irradiation with MPA + T, or the individual steroids with or without GnRH antagonist (GnRH-ant), or GnRH-ant alone, or T + E2. Whereas GnRH-ant alone stimulated differentiation in 55% of tubules 13 wk after irradiation compared with 0% in irradiated-only rats, the addition of MPA reduced the percentage of tubules showing differentiation to 18%. However, T or MPA alone or the combination of the two induced germ cell differentiation in only 2-4% of tubules. In contrast, E2 stimulated differentiation in 88% of tubules, and T combined with E2 still resulted in differentiation in 30% of tubules. Although both MPA and E2 suppressed ITT levels to approximately 2% of control (2 ng/g testis), MPA was a less effective stimulator of spermatogenic recovery than E2 or GnRH-ant alone. MPA's function as a weak androgen was likely responsible for inhibiting spermatogenic recovery, as was the case for all other tested androgens. Thus, for clinical protection or restoration of spermatogenesis after radiation or chemotherapy by suppressing T production, MPA, at least in the doses used in the present study, is suboptimal. The combination of an estrogen with T appears to be most effective for stimulating such recovery. 相似文献
67.
Discovery and characterization of a selective, nonpeptidyl thrombopoietin receptor agonist 总被引:2,自引:0,他引:2
Erickson-Miller CL DeLorme E Tian SS Hopson CB Stark K Giampa L Valoret EI Duffy KJ Luengo JL Rosen J Miller SG Dillon SB Lamb P 《Experimental hematology》2005,33(1):85-93
OBJECTIVE: Peptide and other small molecule agonists have been described for several cytokines and growth factors. Hydrazone compounds described here as thrombopoietin receptor agonists were identified as activating STAT proteins in a Tpo responsive cell line. METHODS: STAT activation and analysis of signal transduction pathways in cell lines and normal human platelets was elucidated by Western blot and electrophoretic mobility shift assays. Proliferation assays in cell types responsive to other cytokines determined specificity for Tpo receptor. Flow cytometry quantified differentiation of CD34(+) cells into CD41(+) megakaryocytes and platelet production in vitro. RESULTS: Activation of STAT5, mitogen-activated protein kinase, p38, and early response genes by SB 394725 was similar to that induced by Tpo. SB 394725 induced a reporter gene response under a STAT activation promoter as well as the megakaryocyte-specific gpIIb promoter. The compound induced proliferation of Tpo responsive lines but demonstrated no activity in cell lines responding to other cytokines, i.e., erythropoietin, granulocyte-colony stimulating factor, interleukin-3, interferon-gamma. The response of normal human Tpo receptors was elucidated by measuring growth and differentiation of human bone marrow in vitro. Activation of endogenous Tpo receptors by SB 394725 was demonstrated in human and chimp platelets, but not in platelets of other species including mouse, dog, rabbit, or cynomolgus monkey. CONCLUSIONS: SB 394725, a small molecule with a molecular weight of 452 Da, is capable of activating Tpo-specific signal transduction, proliferation, and differentiation responses similar to the responses and functions of the protein growth factor, Tpo. 相似文献
68.
Jessica L. de Beer Jakko van Ingen Gerard de Vries Connie Erkens Maruschka Sebek Arnout Mulder Rosa Sloot Anne-Marie van den Brandt Mimount Enaimi Kristin Kremer Philip Supply Dick van Soolingen 《Journal of clinical microbiology》2013,51(4):1193-1198
In order to switch from IS6110 and polymorphic GC-rich repetitive sequence (PGRS) restriction fragment length polymorphism (RFLP) to 24-locus variable-number tandem-repeat (VNTR) typing of Mycobacterium tuberculosis complex isolates in the national tuberculosis control program in The Netherlands, a detailed evaluation on discriminatory power and agreement with findings in a cluster investigation was performed on 3,975 tuberculosis cases during the period of 2004 to 2008. The level of discrimination of the two typing methods did not differ substantially: RFLP typing yielded 2,733 distinct patterns compared to 2,607 in VNTR typing. The global concordance, defined as isolates labeled unique or identically distributed in clusters by both methods, amounted to 78.5% (n = 3,123). Of the remaining 855 cases, 12% (n = 479) of the cases were clustered only by VNTR, 7.7% (n = 305) only by RFLP typing, and 1.8% (n = 71) revealed different cluster compositions in the two approaches. A cluster investigation was performed for 87% (n = 1,462) of the cases clustered by RFLP. For the 740 cases with confirmed or presumed epidemiological links, 92% were concordant with VNTR typing. In contrast, only 64% of the 722 cases without an epidemiological link but clustered by RFLP typing were also clustered by VNTR typing. We conclude that VNTR typing has a discriminatory power equal to IS6110 RFLP typing but is in better agreement with findings in a cluster investigation performed on an RFLP-clustering-based cluster investigation. Both aspects make VNTR typing a suitable method for tuberculosis surveillance systems. 相似文献
69.
Changes in the activity and number of natural killer (NK) cells in peripheral blood in patients with autoimmune thyroid disease were examined. NK activity was measured in a 4-hr 51Cr-release assay and the number of NK cells was analyzed with FITC-conjugated monoclonal antibodies by use of an automated flow cytometer. NK activity in patients with untreated Graves' disease (n=25, 39.7+13.5%, P<0.05) and Hashimoto's thyroiditis (n=18, 41.0±14.2%, P<0.05) was high compared to the activity in non-pregnant controls (n=61, 32.6±15.0%). NK activity in patients with postpartum Graves' thyrotoxicosis (n=11, 48.6±18.9%) was markedly increased compared to the activity in non-pregnant controls (P<0.01) and in postpartum controls (n=29, 33.8±15.2%, P<0.05), although the mean ages of each group did not differ significantly. Moreover, NK activities in the thyrotoxic state were significantly higher than those in the euthyroid state in the same patients with postpartum Graves' thyrotoxicosis or with postpartum destructive thyrotoxicosis. The number of CD16 positive cells increased in patients with postpartum Graves' thyrotoxicosis. However the number of CD 16 and CD57 positive cells were normal in all other groups of patients. These results indicate that an increase of NK activity is associated with exacerbation of autoimmune thyroid disease both in Hashimoto's thyroiditis and in Graves' disease and suggest that NK cells might have an important role for the control of disease activity in autoimmune thyroid disease. 相似文献
70.
Connie Marras MD PhD Kelly A. Mills MD Shirley Eberly MS David Oakes PhD Kelvin L. Chou MD PhD Matthew Halverson BA BS Sotirios A. Parashos MD PhD Christopher G. Tarolli MD MHPE Jin-Shei Lai PhD Cindy J. Nowinsky MD PhD Oksana Suchowersky MD Eric S. Farbman MD Lisa M. Shulman MD Tanya Simuni MD 《Movement disorders》2021,36(8):1979-1983