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van Sighem A Danner S Ghani AC Gras L Anderson RM de Wolf F;ATHENA National Observational Cohort Study 《Journal of acquired immune deficiency syndromes (1999)》2005,40(2):212-218
Mortality in HIV-infected patients has decreased dramatically since the introduction of highly active antiretroviral therapy (HAART). We analyzed progression to death in a population of 3678 antiretroviral treatment-naive patients from the ATHENA national observational cohort from 24 weeks after the start of HAART. Mortality was compared with that in the general population in the Netherlands matched by age and gender. Only log-transformed CD4 cell count (hazard ratio [HR] = 0.50, 95% confidence interval [CI]: 0.40 to 0.61 per unit increase) and plasma viral load (HR = 0.30, 95% CI: 0.15 to 0.60, HIV RNA level <100,000 vs. > or = 100,000 copies/mL) measured at 24 weeks and infection via intravenous drug use (IDU) (HR = 0.16, 95% CI: 0.10 to 0.26, non-IDU vs. IDU) were significantly associated with progression to death. For non-IDU patients with 600 x 10 CD4 cells/L and an HIV RNA level <100,000 copies/mL at 24 weeks, mortality was predicted to be 5.3 (95% CI: 3.5 to 8.4) and 10.4 (95% CI: 6.4 to 17.4) times higher than in the general population for 25-year-old men and women, respectively, and 1.15 (95% CI: 1.08 to 1.25) and 1.29 (95% CI: 1.16 to 1.50) times higher for 65-year-old men and women, respectively. Hence, mortality in HIV-infected patients with a good initial response to HAART is still higher than in the general population. 相似文献
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Role of endotoxemia in cardiovascular dysfunction and lethality: virulent and nonvirulent Escherichia coli challenges in a canine model of septic shock.
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W D Hoffman R L Danner Z M Quezado S M Banks R J Elin J M Hosseini C Natanson 《Infection and immunity》1996,64(2):406-412
We investigated whether the severity of septic shock is determined by virulence factors associated with or the levels of endotoxemia produced by two Escherichia coli strains. Canines were challenged intraperitoneally with an E. coli strain (O6:H1:K2) that has virulence factors associated with human disease or with an equal dose of a nonvirulent strain (O86:H8) that lacks these factors. Both strains were administered in viable, heat-killed, and purified endotoxin forms. Median survival times with the virulent strain compared with the nonvirulent strain were shorter with viable bacteria (5 x 10(10) CFU/kg) (144 h versus > 672 h; Wilcoxon, P = 0.03), longer with heat-killed bacteria (5 x 10(9) CFU/kg) ( > 676 h versus 26 h; P = 0.03), and similar with purified endotoxin (15 mg/kg) (28 h versus 48 h; P = 0.71). However, whether the challenge contained viable bacteria, heat-killed bacteria, or purified endotoxin, the virulent strain produced less endotoxemia (P = 0.001). Hence, the changing outcomes with differing forms of the two strains cannot be attributed solely to endotoxin levels. The viable virulent strain caused less endotoxemia but more harm, and this does not appear to be explained by a more potent endotoxin or other heat-stable component. This study suggests that circulating endotoxin levels per se are less important in the outcome of septic shock than virulence factors associated with E. coli strains. Furthermore, the data call into question the significance of the endotoxin concentration in the blood in predicting the severity of shock and the lethality of gram-negative infections. 相似文献
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J Frick C Danner G Kunit G Galvan G Bernroider 《International journal of andrology》1980,3(5):469-478
Eighteen boys with either unilateral or bilateral cryptorchidism were treated with a synthetic LH-RH analogue ("D-Leu 6, Des-Gly-10 LH-RH ethylamide") intranasally. The peptide was dissolved in aqueous solution (25 micrograms in 0,2 ml) and administered in the form of nasal drops. The patients were divided in two groups: in group A, 50 micrograms of the synthetic LH-RH analogue were administered intranasally every 48 h for 36 days; in group B same dose was given every 24 h. Additionally, in 4 cases a LH-RH test prior the trial was performed with the same peptide. The nasal administration resulted in a fivefold increase of LH and of FSH plasma concentration in 30 min and in 60 min, respectively. The endocrine profiles for T, LH and FSH were studied in each group over the treatment period and in group B (same dose was given every 24 h) a significant decrease of the LH and FSH plasma levels could be found. The clinical effect of treatment was same in the both groups. In the whole material 44% had either unilateral or bilateral descent of the testis after the therapy. 相似文献
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Glycoprotein (GP) IX is a subunit of the von Willebrand receptor, GPIb-V-IX, which mediates adhesion of platelets to the subendothelium of damaged blood vessels. Previous characterization of the GPIX promoter identified a functional Ets site that, when disrupted, reduced promoter activity. However, the Ets protein(s) that regulated GPIX promoter expression was unknown. In this study, transient cotransfection of several GPIX promoter/reporter constructs into 293T kidney fibroblasts with a Fli-1 expression vector shows that the oncogenic protein Fli-1 can transactivate the GPIX promoter when an intact GPIX Ets site is present. In addition, Fli-1 binding of the GPIX Ets site was identified in antibody supershift experiments in nuclear extracts derived from hematopoietic human erythroleukemia cells. Comparative studies showed that Fli-1 was also able to transactivate the GPIbalpha and, to a lesser extent, the GPIIb promoter. Immunoblot analysis identified Fli-1 protein in lysates derived from platelets. In addition, expression of Fli-1 was identified immunohistochemically in megakaryocytes derived from CD34(+) cells treated with the megakaryocyte differentiation and proliferation factor, thrombopoietin. These results suggest that Fli-1 is likely to regulate lineage-specific genes during megakaryocytopoiesis. 相似文献
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Atanaska Marinova‐Petkova Georgi Georgiev Todor Petkov Daniel Darnell John Franks Ghazi Kayali David Walker Patrick Seiler Angela Danner Allison Graham Pamela McKenzie Scott Krauss Richard J. Webby Robert G. Webster 《Influenza and other respiratory viruses》2016,10(2):98-108