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981.
982.
Deterding RR Lavange LM Engels JM Mathews DW Coquillette SJ Brody AS Millard SP Ramsey BW;for the Cystic Fibrosis Therapeutics Development Network the Inspire - Working Group 《American journal of respiratory and critical care medicine》2007,176(4):362-369
RATIONALE: Denufosol tetrasodium is a selective P2Y(2) agonist that enhances mucosal hydration and mucus clearance by activating Cl(-) secretion and inhibiting epithelial Na(+) transport through a non-cystic fibrosis transmembrane conductance regulator mechanism in the lung. OBJECTIVES: To examine the safety and efficacy of 28 days of treatment with denufosol compared with placebo in patients with mild cystic fibrosis. METHODS: The study was a randomized, double-blind, multi-center, 28-day, phase 2 clinical trial of denufosol tetrasodium inhalation solution (20, 40, or 60 mg) versus placebo (normal saline). Patients with screening FEV(1) >or= 75% of predicted normal value and not treated with inhaled antibiotics for the past 30 days were randomized to receive one of three doses of denufosol or placebo administered three times daily. MEASUREMENTS AND MAIN RESULTS: Eighty-nine patients were randomized and received the study drug, 94% completed the study, and 98% were compliant with dosing. All treatments were generally well tolerated, with no dose-response trends observed with respect to safety parameters. The most common adverse event was cough (52% of placebo patients and 47% of denufosol patients). Five patients discontinued early due to adverse events, two on placebo and three on denufosol. Denufosol patients (pooling active doses) had significantly higher changes from baseline in FEV(1) (P = 0.006), FEF(25%-75%) (P = 0.008), FVC (P = 0.022), and FEV(1)/FVC (P = 0.047) than placebo patients at the end of the study. CONCLUSIONS: Denufosol administered three times daily for 28 days appeared to be safe and well tolerated in this population with mild cystic fibrosis and provided preliminary evidence of potential benefit in lung function. 相似文献
983.
Mellars P Gravina B Bronk Ramsey C 《Proceedings of the National Academy of Sciences of the United States of America》2007,104(9):3657-3662
The nature of the replacement of Neanderthal by anatomically and behaviorally modern populations in Europe is currently a topic of lively debate in human evolution. In an earlier paper [Gravina B, Mellars P, Bronk Ramsey C (2005) Nature 483:51-56], we published a series of radiocarbon accelerator mass spectrometer measurements for the site of Chatelperron in central France, which had been claimed to show a clear "interstratification" of successive levels of Neanderthal and modern human occupation, on the basis of excavations carried out by Henri Delporte in the 1950s. This interpretation has recently been challenged by Zilh?o and colleagues [Zilh?o J, d'Errico F, Bordes J-G, Lenoble A, Texier J-P, Rigaud J-P (2006) Proc Natl Acad Sci USA 103:12643-12648], who suggest that the deposits excavated in the 1950s consisted largely, if not entirely, of the unstratified "backdirt" of the earlier, 19th century excavations on the site. We show here that the excavation backdirt interpretation for the Chatelperron stratigraphy can be refuted from many different aspects of the stratigraphic, radiocarbon, and archaeological evidence. We reassess the significance of this site for current models of the coexistence and interactions between Neanderthal and anatomically modern populations in western Europe. 相似文献
984.
985.
Angelotta C McKoy JM Fisher MJ Buffie CG Barfi K Ramsey G Frohlich L Bennett CL 《Vox sanguinis》2007,93(2):159-165
BACKGROUND: Since the first cases of acquired immunodeficiency syndrome in persons with haemophilia were reported in 1982, much has been written about the consequences of human immunodeficiency virus (HIV) contamination of the blood supply. Relatively little attention has been paid to similar hepatitis C virus (HCV) concerns since the first cases of HCV-infected persons with haemophilia were identified in 1989. METHODS: We review the history, public health, policy, and financial consequences of blood supply policy decisions made for persons with haemophilia who received HCV-contaminated blood products in eight countries that were severely impacted by viral contamination of the blood supply during the 1980s, contrasting these findings with those reported previously for HIV contamination of the blood supply during the same time-period. A Medline search and a hand search of retrieved bibliographies of English-language articles on HCV concerns in haemophilia patients published from 1989 to 2006 were performed. RESULTS: Our review identified that two- to eightfold more persons with haemophilia in the eight countries contracted HCV vs. HIV from contaminated blood products during the 1980s. Opportunistic infections and immunosuppression-related complications among persons with haemophilia developed shortly after these patients received HIV-infected blood products whereas hepatic complications among HCV-infected persons with haemophilia are just now being diagnosed two decades after these individuals received HCV-contaminated blood products. Policy makers in four countries conducted official public inquiries into blood safety decisions related to HIV- and/or HCV-contamination of the blood supply. More than 20 countries allocated compensation funds for HIV-infected persons with haemophilia (mean award ranging from $37 000 to 400 000) whereas only the UK, Canada, and Ireland allocated compensation funds for HCV-infected persons with haemophilia (mean award ranging from $37 000 to 50 000). CONCLUSION: While the clinical impact among persons with haemophilia of HCV contamination of the blood supply in the 1980s was larger than the impact of HIV contamination of the blood supply during this time-period, the policy response was smaller. Consideration should be given to adopting support programmes for HCV-infected persons with haemophilia in countries that do not have these programs. 相似文献
986.
We used functional magnetic resonance imaging to examine the neuroanatomical correlates of visual hallucinations in a patient with a left visual field defect who had suffered bilateral occipital infarction. By cross-correlating the functional magnetic resonance imaging data with the hallucination events, we were able to identify the cerebral activity underlying the hallucinations. Bilateral activation was observed during visual stimulation in the calcarine fissure and the same activation was found medially in the left and right occipital cortex adjacent to the infarcted areas. This pattern of perilesional visual cortex activation is consistent with the suggestion that primary sensory areas may be involved in visual hallucinations after stroke. 相似文献
987.
Atomoxetine ADHD Comorbid MDD Study Group Bangs ME Emslie GJ Spencer TJ Ramsey JL Carlson C Bartky EJ Busner J Duesenberg DA Harshawat P Kaplan SL Quintana H Allen AJ Sumner CR 《Journal of child and adolescent psychopharmacology》2007,17(4):407-420
This double-blind study examined efficacy and safety of atomoxetine (ATX; < or =1.8mg/kg per day) in adolescents aged 12-18 with Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnoses of both attention-deficit/hyperactivity disorder (ADHD) and co-morbid major depressive disorder (MDD). Diagnoses were confirmed by the Kiddie Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version and persistently elevated scores on the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV, Parent version, Investigator-administered and -scored (ADHDRS-IV-Parent:Inv, > or =1.5 standard deviations above age and gender norms) and Children's Depression Rating Scale-Revised (CDRS-R, > or = 40). Patients were treated for approximately 9 weeks with ATX (n = 72) or placebo (n = 70). Mean decrease in ADHDRS-IV-Parent:Inv total score was significantly greater in the ATX group (-13.3 +/- 10.0) compared with the placebo group (-5.1 +/- 9.9; p < 0.001). Mean CDRS-R score improvement was not significantly different between groups (ATX, -14.8 +/- 13.3; placebo, -12.8 +/- 10.4). Rates of treatment-emergent mania did not differ between groups (ATX, 0.0%; placebo, 1.5%). ATX treatment was associated with significantly more nausea and decreased appetite (p = 0.002; p = 0.003). No spontaneously reported adverse events involving suicidal ideation or suicidal behavior occurred in either group. ATX was an effective and safe treatment for ADHD in adolescents with ADHD and MDD. However, this trial showed no evidence for ATX of efficacy in treating MDD. 相似文献
988.
989.
Seibert RM Ramsey CR Hines JW Kupelian PA Langen KM Meeks SL Scaperoth DD 《International journal of radiation oncology, biology, physics》2007,67(2):601-609
PURPOSE: Volumetric computed tomography (CT) images acquired by image-guided radiation therapy (IGRT) systems can be used to measure tumor response over the course of treatment. Predictive adaptive therapy is a novel treatment technique that uses volumetric IGRT data to actively predict the future tumor response to therapy during the first few weeks of IGRT treatment. The goal of this study was to develop and test a model for predicting lung tumor response during IGRT treatment using serial megavoltage CT (MVCT). METHODS AND MATERIALS: Tumor responses were measured for 20 lung cancer lesions in 17 patients that were imaged and treated with helical tomotherapy with doses ranging from 2.0 to 2.5 Gy per fraction. Five patients were treated with concurrent chemotherapy, and 1 patient was treated with neoadjuvant chemotherapy. Tumor response to treatment was retrospectively measured by contouring 480 serial MVCT images acquired before treatment. A nonparametric, memory-based locally weight regression (LWR) model was developed for predicting tumor response using the retrospective tumor response data. This model predicts future tumor volumes and the associated confidence intervals based on limited observations during the first 2 weeks of treatment. The predictive accuracy of the model was tested using a leave-one-out cross-validation technique with the measured tumor responses. RESULTS: The predictive algorithm was used to compare predicted verse-measured tumor volume response for all 20 lesions. The average error for the predictions of the final tumor volume was 12%, with the true volumes always bounded by the 95% confidence interval. The greatest model uncertainty occurred near the middle of the course of treatment, in which the tumor response relationships were more complex, the model has less information, and the predictors were more varied. The optimal days for measuring the tumor response on the MVCT images were on elapsed Days 1, 2, 5, 9, 11, 12, 17, and 18 during treatment. CONCLUSIONS: The LWR model accurately predicted final tumor volume for all 20 lung cancer lesions. These predictions were made using only 8 days' worth of observations from early in the treatment. Because the predictions are accurate with quantified uncertainty, they could eventually be used to optimize treatment. 相似文献
990.