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51.
Effect of antituberculosis drug resistance on response to treatment and outcome in adults with tuberculous meningitis 总被引:5,自引:0,他引:5
Thwaites GE Lan NT Dung NH Quy HT Oanh DT Thoa NT Hien NQ Thuc NT Hai NN Bang ND Lan NN Duc NH Tuan VN Hiep CH Chau TT Mai PP Dung NT Stepniewska K White NJ Hien TT Farrar JJ 《The Journal of infectious diseases》2005,192(1):79-88
BACKGROUND: Tuberculous meningitis (TBM) caused by Mycobacterium tuberculosis resistant to 1 or more antituberculosis drugs is an increasingly common clinical problem, although the impact on outcome is uncertain. METHODS: We performed a prospective study of 180 Vietnamese adults admitted consecutively for TBM. M. tuberculosis was cultured from the cerebrospinal fluid (CSF) of all patients and was tested for susceptibility to first-line antituberculosis drugs. Presenting clinical features, time to CSF bacterial clearance, clinical response to treatment, and 9-month morbidity and mortality were compared between adults infected with susceptible and those infected with drug-resistant organisms. RESULTS: Of 180 isolates, 72 (40.0%) were resistant to at least 1 antituberculosis drug, and 10 (5.6%) were resistant to at least isoniazid and rifampicin. Isoniazid and/or streptomycin resistance was associated with slower CSF bacterial clearance but not with any differences in clinical response or outcome. Combined isoniazid and rifampicin resistance was strongly predictive of death (relative risk of death, 11.63 [95% confidence interval, 5.21-26.32]) and was independently associated with human immunodeficiency virus infection. CONCLUSIONS: Isoniazid and/or streptomycin resistance probably has no detrimental effect on the outcome of TBM when patients are treated with first-line antituberculosis drugs, but combined isoniazid and rifampicin resistance is strongly predictive of death. 相似文献
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Thanh Thi Nguyen Ngoc-Phuong Thi Le The Thai Nguyen Phuong Hoang Tran 《RSC advances》2019,9(65):38148
A mild and highly efficient reaction for the synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles catalyzed by a magnetically supported Lewis acidic deep eutectic solvent on magnetic nanoparticles (LADES@MNP) has been developed via one-pot multicomponent processes under solvent-free sonication. These reactions have good to excellent yields, mild conditions, and work-up simplicity. This method represents a new method for the preparation of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles. More importantly, LADES@MNP can be easily recovered by magnetic separation and reused five times without significant loss of catalytic activity.A mild and highly efficient method for the synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles catalyzed by a Lewis acidic deep eutectic solvent on magnetic nanoparticles (LADES@MNP). 相似文献
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Alexandre Marchand Jean‐Antoine Martin David Collot Olivier Hoang Ingrid Roulland Florian Semence Pierre‐Edouard Sottas Michel Audran Emmanuelle Varlet‐Marie 《Drug testing and analysis》2019,11(11-12):1698-1713
The combination of growth hormone (GH) and recombinant erythropoietin (rEPO) is thought to be used particularly in endurance sports. Our objective was to reproduce a 2‐week administration of rEPO microdoses alone or in combination with GH microdoses (three times a week) on healthy and athletic male subjects and to evaluate if GH had any additional effects compared to EPO treatment alone. The effects of the treatments on hematological parameters and VO2max were studied as well as the detection of GH in serum. While the rEPO microdose regimen was associated with a significant increase in reticulocytes, no clear elevation in hemoglobin concentration (HGB) was observed. Using a correction by plasma volume did not reveal more effects of EPO on HGB. Our results did not show any additional effect when the GH microdoses were co‐administered. In addition, no clear increase in VO2max was observed after treatment, with an elevation in only half the subjects in both groups (EPO and EPO+GH). A clear effect of GH on insulin‐like growth factor I (IGF‐I) was seen but it was lower on procollagen III amino‐terminal propeptide (P‐III‐NP). GH detection using the direct isoform test identified only one subject 24 hours after receiving GH. The GH biomarker test combining IGF‐I and P‐III‐NP was not able to detect the GH administration. However, a longitudinal follow‐up of the intraindividual variations showed a significant increase in IGF‐I 24 and 48 hours after GH administration in most subjects, while the effect of GH microdoses on P‐III‐NP was less straightforward. 相似文献
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Kristine Yaffe MD Manjula Kurella‐Tamura MD MPH Lynn Ackerson PhD Tina D. Hoang MSPH Amanda H. Anderson PhD Mark Duckworth MPH Alan S. Go MD Marie Krousel‐Wood MD MSPH John W. Kusek PhD James P. Lash MD Akinlolu Ojo MD PhD Nancy Robinson PhD Ashwini R. Sehgal MD James H. Sondheimer MD Susan Steigerwalt MD Raymond R. Townsend MD the CRIC Study Investigators 《Journal of the American Geriatrics Society》2014,62(9):1623-1629
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Jingling Liao Chun-Xiang Wu Christopher Burlak Sheng Zhang Heather Sahm Mu Wang Zhong-Yin Zhang Kurt W. Vogel Mark Federici Steve M. Riddle R. Jeremy Nichols Dali Liu Mark R. Cookson Todd A. Stone Quyen Q. Hoang 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(11):4055-4060
Mutation in leucine-rich-repeat kinase 2 (LRRK2) is a common cause of Parkinson disease (PD). A disease-causing point mutation R1441H/G/C in the GTPase domain of LRRK2 leads to overactivation of its kinase domain. However, the mechanism by which this mutation alters the normal function of its GTPase domain [Ras of complex proteins (Roc)] remains unclear. Here, we report the effects of R1441H mutation (RocR1441H) on the structure and activity of Roc. We show that Roc forms a stable monomeric conformation in solution that is catalytically active, thus demonstrating that LRRK2 is a bona fide self-contained GTPase. We further show that the R1441H mutation causes a twofold reduction in GTPase activity without affecting the structure, thermal stability, and GDP-binding affinity of Roc. However, the mutation causes a twofold increase in GTP-binding affinity of Roc, thus suggesting that the PD-causing mutation R1441H traps Roc in a more persistently activated state by increasing its affinity for GTP and, at the same time, compromising its GTP hydrolysis.Mutation in leucine-rich-repeat kinase 2 (LRRK2) is a common cause of Parkinson disease (PD) (1–5). LRRK2 is a large (2,527-aa) multidomain protein consisting of seven putative domains (2), including a Ras-like GTPase domain called Ras of complex proteins (Roc), followed by a domain called C-terminal of Roc (COR), which is then followed by a kinase domain (Kin). It remains unclear how perturbations of these activities result in disease; however, the most common mutation in LRRK2-associated PD, G2019S in the kinase domain, shows higher kinase activity than wild type; therefore, its overactivation might be associated with disease pathogenesis (6).The tandem Roc-COR-Kin arrangement suggests that their activities might be coupled such that the GTPase activity of Roc might modulate the kinase activity. Indeed, several studies have shown that GTP binding to the Roc domain regulates the activity of the Kin domain (7, 8). Moreover, a PD-associated mutation in the Roc domain (R1441C) has been shown to have higher kinase activity (9), thus suggesting that mutations in the Roc domain, also up-regulate kinase activity.Understanding the function of Roc and its mechanism of action is important for understanding the mechanism of PD pathogenesis and therapeutic development. However, because of the lack sufficient quantity of protein samples amendable for detailed investigations, the biochemical properties and enzymatic activities of the Roc domain of LRRK2 are poorly understood.Here, we describe a stably folded construct of human Roc domain that enabled us to investigate quantitatively its biochemical and enzymatic properties. The results revealed that a PD-causing mutation R1441H in the Roc domain renders it less active at hydrolyzing GTP, as well as having higher affinity for GTP, than its wild-type counterpart, thereby increasing the residence time of its GTP-bound “active state,” which is associated with PD pathogenesis (8). 相似文献
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Hoang Huong Thi Xuan Molassiotis Alex Chan Choi Wan Nguyen Thi Huong Liep Nguyen Van 《Sleep & breathing》2020,24(1):241-251
Sleep and Breathing - Although insomnia is common among cancer patients, its prevalence remains variable, and its risk factors and correlation with other cancer-related symptoms are not fully... 相似文献
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