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排序方式: 共有1154条查询结果,搜索用时 15 毫秒
101.
Jennifer Werkheiser Teresa Gomez Shreya Parekh David A. Baron 《Pharmacology, biochemistry, and behavior》2009,92(3):543-548
Icilin is a cold channel agonist that produces vigorous wet-dog shaking in rats. The shaking is accompanied by an increase in the level of extracellular glutamate in the brain. Hence, we hypothesized that icilin-induced wet-dog shakes are dependent on increased glutamatergic transmission and nitric oxide (NO) production. Rats injected with icilin (0.5, 1, 2.5, 5 mg/kg, i.p.) displayed a dose-related increase in wet-dog shakes. Pretreatment with LY 235959 (1, 2 mg/kg, i.p.), a NMDA receptor antagonist, or L-NAME (50 mg/kg, i.p.), a NO synthase (NOS) inhibitor, attenuated icilin-induced wet-dog shakes. The shaking was also reduced by intracerebroventricular L-NAME (1 mg/rat, i.c.v.) administration, indicating that the stimulant effect of icilin is dependent on central NO production. Pretreatment with 6,7-dinitroquinoxaline-2,3(1H,4H)-dione (DNQX) (10, 20 mg/kg, i.p.), an AMPA receptor antagonist, or ceftriaxone (200 mg/kg, i.p. for 5 days), a beta-lactam antibiotic and glutamate transporter subtype 1 (GLT-1) activator, did not alter the incidence of icilin-induced shaking. The present data reveal that icilin produces behavioral stimulation by a mechanism requiring NMDA receptor activation and nitric oxide production and suggest that glutamate and NO signaling play important roles in cold channel pharmacology. 相似文献
102.
Doshi AA Orsini AR Mazzaferri EL Schmidt WT Magorien RD Bush CA 《International journal of cardiology》2007,118(3):e87-e88
Myocardial bridging is the most common congenital coronary abnormality, and is frequently found on post-mortem cardiac examination. Although often asymptomatic, clinical presentation can vary from unstable angina to sudden cardiac death. Only isolated cases of using drug eluting stents (DES) for bridging segments have been described. Our objective was to retrospectively analyze a series of patients undergoing percutaneous coronary intervention (PCI) with DES for symptomatic myocardial bridging and follow post-procedure outcomes. Results revealed favorable peri-procedural angiographic and short-term clinical results with DES implantation. Although initial data regarding DES implantation for symptomatic myocardial bridging are promising, long-term follow up, particularly related to in-stent restenosis will be important. 相似文献
103.
de Boer R Clemens M Renczes G Kotasek D Prausova J Marschner N Hedenus M Doshi S Hendricks L Österborg AC 《Medical oncology (Northwood, London, England)》2011,28(4):1210-1217
AMG 114 is a novel, hyperglycosylated erythropoiesis-stimulating agent. In preclinical studies, AMG 114 demonstrated increased
potency and longer half-life than darbepoetin alfa and epoetin alfa. This phase I/II, randomised, double-blind, placebo-controlled,
dose-escalation study evaluated safety, pharmacokinetics, and efficacy of AMG 114 in patients with non-myeloid malignancies
and chemotherapy-induced anaemia. Patients were randomised (1:5) to receive subcutaneous placebo or AMG 114 Q3W for 6 weeks
in 3 dose cohorts of 15 μg (cohort A1), 50 μg (cohort A2), or 200 μg (cohort A3). Safety endpoints included incidence of adverse
events and dose-limiting toxicities (DLTs). The PK profile of AMG 114 was evaluated. Efficacy was assessed by change in haemoglobin
from baseline to end of treatment. Forty-eight patients enrolled: 8 received placebo, 40 received AMG 114. No DLTs were observed;
adverse events were consistent with underlying malignancies. The PK profile was dose-proportional over the dose range tested;
terminal half-life of AMG 114 was approximately 130 h. Mean change (range) in haemoglobin from baseline in AMG 114-treated
patients was −0.16 (−1.8 to 1.3), 0.21 (−1.5 to 3.4), and 0.76 (−1.0 to 2.9) g/dl in cohorts A1, A2, and A3, respectively.
AMG 114 appeared to be well tolerated, but the study was halted, in part because of modest efficacy. 相似文献
104.
Hong Lin Stefano Vicini Fu-Chun Hsu Shachee Doshi Hajime Takano Douglas A. Coulter David R. Lynch 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(38):16661-16666
In association with NMDA receptors (NMDARs), neuronal α7 nicotinic ACh receptors (nAChRs) have been implicated in neuronal plasticity as well as neurodevelopmental, neurological, and psychiatric disorders. However, the role of presynaptic NMDARs and their interaction with α7 nAChRs in these physiological and pathophysiological events remains unknown. Here we report that axonal α7 nAChRs modulate presynaptic NMDAR expression and structural plasticity of glutamatergic presynaptic boutons during early synaptic development. Chronic inactivation of α7 nAChRs markedly increased cell surface NMDAR expression as well as the number and size of glutamatergic axonal varicosities in cortical cultures. These boutons contained presynaptic NMDARs and α7 nAChRs, and recordings from outside-out pulled patches of enlarged presynaptic boutons identified functional NMDAR-mediated currents. Multiphoton imaging of presynaptic NMDAR-mediated calcium transients demonstrated significantly larger responses in these enlarged boutons, suggesting enhanced presynaptic NMDAR function that could lead to increased glutamate release. Moreover, whole-cell patch clamp showed a significant increase in synaptic charge mediated by NMDAR miniature EPSCs but no alteration in the frequency of AMPAR miniature EPSCs, suggesting the selective enhancement of postsynaptically silent synapses upon inactivation of α7 nAChRs. Taken together, these findings indicate that axonal α7 nAChRs modulate presynaptic NMDAR expression and presynaptic and postsynaptic maturation of glutamatergic synapses, and implicate presynaptic α7 nAChR/NMDAR interactions in synaptic development and plasticity. 相似文献
105.
Daniel Polsky Jalpa A. Doshi José Escarce Willard Manning Susan M. Paddock Liyi Cen Jeannette Rogowski 《Health services research》2009,44(3):926-945
Objective. To determine whether Medicare enrollment at age 65 has an effect on the health trajectory of the near-elderly uninsured.
Data Sources. Eight biennial waves (1992–2006) of the Health and Retirement Study, a nationally representative panel survey of noninstitutionalized 51–61 year olds and their spouses.
Study Design. We use a quasi-experimental approach to compare the health effects of insurance for the near-elderly uninsured with previously insured contemporaneous controls. The primary outcome measure is overall self-reported health status combined with mortality (i.e., excellent to very good, good, fair to poor, dead).
Results. The change in the trajectory of overall health status for the previously uninsured that can be attributed to Medicare is small and not statistically significant. For every 100 persons in the previously uninsured group, joining Medicare is associated with 0.6 fewer in excellent or very good health (95 percent CI: −4.8, 3.3), 0.3 more in good health (95 percent CI: −3.8, 4.1), 2.5 fewer in fair or poor health (95 percent CI: −7.4, 2.3), and 2.8 more dead (−4.0, 10.0) by age 73. The health trajectory patterns from physician objective health measures are similarly small and not statistically significant.
Conclusions. Medicare coverage at age 65 for the previously uninsured is not linked to improvements in overall health status. 相似文献
Data Sources. Eight biennial waves (1992–2006) of the Health and Retirement Study, a nationally representative panel survey of noninstitutionalized 51–61 year olds and their spouses.
Study Design. We use a quasi-experimental approach to compare the health effects of insurance for the near-elderly uninsured with previously insured contemporaneous controls. The primary outcome measure is overall self-reported health status combined with mortality (i.e., excellent to very good, good, fair to poor, dead).
Results. The change in the trajectory of overall health status for the previously uninsured that can be attributed to Medicare is small and not statistically significant. For every 100 persons in the previously uninsured group, joining Medicare is associated with 0.6 fewer in excellent or very good health (95 percent CI: −4.8, 3.3), 0.3 more in good health (95 percent CI: −3.8, 4.1), 2.5 fewer in fair or poor health (95 percent CI: −7.4, 2.3), and 2.8 more dead (−4.0, 10.0) by age 73. The health trajectory patterns from physician objective health measures are similarly small and not statistically significant.
Conclusions. Medicare coverage at age 65 for the previously uninsured is not linked to improvements in overall health status. 相似文献
106.
107.
Ye X Sikirica V Schein JR Grant R Zarotsky V Doshi D Benson CJ Riedel AA 《Clinical therapeutics》2008,30(2):358-371
Background: Macrolide antibiotics and fluoroquinolones are extensively used in the treatment of community-acquired pneumonia (CAP). Objective: This analysis was conducted to compare treatment failure rates and health care utilization and cost outcomes among patients with CAP treated with levo-floxacin (500 or 750 mg) or macrolides (azithromycin, clarithromycin, or erythromycin) in an outpatient setting. Methods: This was a retrospective analysis of claims data from a large US health plan. Patients were aged >/=18 years and had a primary diagnosis of CAP that was treated with oral levofloxacin or a macrolide in an outpatient setting (including physicians' offices, outpatient clinics, urgent care centers, and large ambulatory health centers). Patients were followed for 30 days after the index drug date to measure study outcomes. Multivariate regression analysis and a propensity score technique were used to compare rates of treatment failure and CAP-related health care utilization and costs. Two post hoc subgroup analyses were conducted in patients aged >/=50 and >/=65 years. Results: Of the 7526 patients meeting the inclusion criteria, 2968 (39.4%) were treated with levofloxacin and 4558 (60.6%) with a macrolide. Unadjusted rates of treatment failure were 21.1% and 22.7% in the levofloxacin and macrolide cohorts, respectively. After adjustment for demographic characteristics, baseline comorbidities, and severity of illness, levofloxacin recipients were significantly less likely to experience treatment failure than macrolide recipients (odds ratio [OR] = 0.84; 95% CI, 0.75-0.94, P = 0.003). The likelihood of treatment failure was significantly lower in levofloxacin recipients aged >/=50 years (OR = 0.79; 95% CI, 0.66-0.94; P = 0.007) and >/=65 years (OR = 0.65; 95% CI, 0.43-1.00; P = 0.049) compared with the corresponding subgroups of macrolide recipients. The magnitude of this difference was greatest in the subgroup aged >/=65 years, which had a 35% reduced risk of treatment failure compared with the corresponding group of macrolide-treated patients. The rate of CAP-related emergency department visits was significantly lower among patients receiving levofloxa-cin (OR = 0.68; 95% CI, 0.51-0.91; P = 0.009); there were no differences in CAP-related hospitalizations or total CAP-related health care costs between levofloxa-cin and macrolide recipients. Conclusions: Multivariate-adjusted rates of treatment failure in outpatients with CAP were significantly lower in those treated with levofloxacin relative to those treated with a macrolide. The lower rates of treatment failure with levofloxacin were consistently observed across all patients and in the subgroups aged >/=50 and >/=65 years. Rates of emergency department visits were also significantly lower among levofloxacin-treated patients, whereas overall CAP-related hospitali-zations and costs did not differ significantly between the 2 treatment groups. 相似文献
108.
Martin DO Stolen KQ Brown S Yu Y Christie C Doshi SK Smith JM Gold MR Day JD 《American heart journal》2007,153(1):7-13
BACKGROUND: Cardiac resynchronization therapy (CRT) has been demonstrated to be an effective heart failure (HF) therapy. All pivotal trials of CRT to date have used atrial-synchronous biventricular pacing wherein there is no or minimal atrial pacing. In clinical practice, however, physicians often program CRT devices to have atrial rate support pacing, either by increasing the lower rate limit or by activating the rate sensor. OBJECTIVE: The purpose of this study is to evaluate the effect of empiric atrial support pacing in patients with HF who have received a CRT defibrillator (CRT-D) device. METHODS: PEGASUS CRT is a multicenter, 3-arm, randomized clinical trial of approximately 1200 patients receiving a CRT-D device. For the first 6 weeks after implant, devices are programmed to DDD with a lower rate limit of 40 beats/min. At 6 weeks, patients are randomized to DDD-40, DDD-70, or DDDR-40. All randomized patients are followed for 1 year, and at each visit, mortality, HF events, quality of life, New York Heart Association class, and atrial and ventricular arrhythmic episodes are evaluated. An exercise substudy will also be conducted, enrolling a minimum of 375 patients. Patients in this substudy will complete 2 cardiopulmonary exercise tests to evaluate the effect pacing mode has on exercise capacity. This randomized controlled trial will address whether empiric atrial support pacing is of clinical benefit to patients with HF who receive a CRT-D device. 相似文献
109.
110.
Bahadir Simsek MD Jaikirshan Khatri MD Laura Young MD Spyridon Kostantinis MD Judit Karacsonyi MD PhD Athanasios Rempakos MD Khaldoon Alaswad MD Farouc A. Jaffer MD PhD Darshan Doshi MD Sevket Gorgulu MD Omer Goktekin MD Jimmy Kerrigan MD Elias V. Haddad MD Stephane Rinfret MD SM Wissam A. Jaber MD William Nicholson MD Oleg Krestyaninov MD Dimitrii Khelimskii MD James W. Choi MD Taral N. Patel MD Brian K. Jefferson MD Steven M. Bradley MD Sunil V. Rao MD Bavana V. Rangan BDS MPH Salman S. Allana MD Yader Sandoval MD M. Nicholas Burke MD Emmanouil S. Brilakis MD PhD Paul B. Poommipanit MD the PROGRESS-CTO investigators 《Catheterization and cardiovascular interventions》2023,101(6):1028-1035