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Dive into the research topics where George A. Taylor is active.

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Featured researches published by George A. Taylor.


Human Gene Therapy | 2003

Phase I Trial of Intranasal and Endobronchial Administration of a Recombinant Adeno-Associated Virus Serotype 2 (rAAV2)-CFTR Vector in Adult Cystic Fibrosis Patients: A Two-Part Clinical Study

Terence R. Flotte; Pamela L. Zeitlin; Thomas C. Reynolds; Alison E. Heald; Patty Pedersen; Suzanne E. Beck; Carol Conrad; Lois Brass-Ernst; Margaret Humphries; Kevin J. Sullivan; Randall C. Wetzel; George A. Taylor; Barrie J. Carter; William B. Guggino

Recombinant adeno-associated serotype 2-based vectors (rAAV2) possess a number of theoretical advantages for cystic fibrosis (CF) gene therapy because they elicit little or no inflammatory response and generally result in stable expression. rAAV2 vectors expressing the cystic fibrosis transmembrane conductance regulator (CFTR) gene have previously been shown to mediate stable correction of the CF defect in CF bronchial epithelial cells and stable expression of CFTR in rabbit and nonhuman primate models. Here we report the results of the first trial initiated with rAAV in humans, a phase I study in 25 adult and adolescent CF patients with mild to moderate lung disease. Doses of the rAAV-CFTR vector (tgAAVCF) ranging from 3 x 10(1) to 1 x 10(9) replication units (RU), which is equivalent to approximately 6 x 10(4) to 2 x 10(12) DNase resistant particles (DRP), were administered to one side of the nose and to the superior segment of the lower lobe of the right lung. Several adverse events were noted prior to and/or after vector delivery, but most of them appeared to be related to the endogenous CF lung disease or a result of the bronchoscopic procedures. Only one of the serious events was judged to be possibly vector-related (based on temporal association), and this event was a pulmonary exacerbation very similar to several others experienced by the same subject in the three months preceding vector delivery. Vector shedding was minimal throughout the study, and serum-neutralizing antibodies were detected after vector delivery to subjects in the highest dosage cohorts. Gene transfer as measured by DNA polymerase chain reaction (PCR) was not observed until cohort 10 in nasal and bronchial epithelia. Sporadic low-level copy numbers suggested gene transfer of anywhere from 0.002 copies per cell up to 0.5 copies per cell was possible; however, DNA PCR was positive in lungs prior to direct dosing suggesting aspiration from the nasal dosing. These data indicate the need for continued evaluation of rAAV-CFTR vectors in additional clinical trials.


Archives of Disease in Childhood-fetal and Neonatal Edition | 2002

Posthaemorrhagic ventricular dilatation in the premature infant: natural history and predictors of outcome

Brendan P. Murphy; Terrie E. Inder; V Rooks; George A. Taylor; N J Anderson; Nina Mogridge; L J Horwood; Joseph J. Volpe

Objective: To investigate the natural history and predictors of outcome of posthaemorrhagic ventriculomegaly in the very low birthweight (VLBW) infant. Methods: All VLBW infants admitted between September 1994 and September 1997 to the neonatal intensive care units of Brigham and Womens Hospital (Boston), Childrens Hospital (Boston), and Christchurch Womens Hospital (New Zealand) with germinal matrix intraventricular haemorrhage (IVH) were identified. All charts and ultrasound scans were reviewed to define the natural history and perinatal and/or postnatal factors of value in prediction of the course of posthaemorrhagic ventriculomegaly. Progressive ventricular dilatation (PVD) was defined from the results of serial cranial ultrasound scans. Results: A total of 248 VLBW infants had evidence of IVH (22% of all VLBW infants, mean (SD) gestational age 26.8 (2.6) weeks). A quarter of the infants exhibited PVD. Spontaneous arrest of PVD occurred without treatment in 38% of infants with PVD. Of the remaining 62% with persistent PVD, 48% received non-surgical treatment only (pharmacological and/or drainage of cerebrospinal fluid by serial lumbar punctures), 34% received surgical treatment with insertion of a ventriculoperitoneal reservoir and/or shunt, and 18% died. The development of PVD after IVH and adverse short term outcome, such as the requirement for surgery, were predicted most strongly by the severity of IVH. Conclusions: These data reflect the natural history of PVD in the 1990s and show that, despite a slight reduction in its overall incidence, there appears to be a more aggressive course, with appreciable mortality and morbidity in the extremely premature infant. The major predictor of adverse short term outcome, defined as death or need for surgical intervention, was the severity of IVH. These findings may be valuable for the management of very small premature infants.


Pediatric Research | 1998

Near Infrared Spectroscopy Detects Cerebral Ischemia during Hypotension in Piglets

Miles Tsuji; Adre J duPlessis; George A. Taylor; Robert Crocker; Joseph J. Volpe

We have previously reported concordant changes in cerebral intravascular oxygenation measured by near infrared spectroscopy (NIRS) and mean arterial blood pressure (MAP) in premature infants. We hypothesized that the cerebral oxygenation changes are caused by MAP-induced alterations in cerebral blood flow (CBF) and studied these parameters in neonatal piglets (n = 6). Changes in cerebral intravascular oxygenation were measured by NIRS from the hemoglobin difference (HbD) signal (oxyhemoglobin-deoxyhemoglobin). CBF was measured by the radioactive microsphere technique. The cerebral circulation was also monitored by Doppler determinations of CBF velocity (time average mean velocity) in the anterior cerebral artery. Hypotension to <50% of baseline MAP was achieved by a ligature around the ascending aorta. Arterial oxygenation was maintained constant by mechanical ventilation. As observed in our studies of premature infants, cerebral HbD and MAP showed concordant changes. Hypotension was accompanied by significant decreases both in CBF (42.8 ± 12.5% of baseline p < 0.01) and HbD (-65.0 ± 22.0 µmol/L·dpf, p < 0.01). HbD was significantly correlated with MAP (p < 0.05) and time average mean velocity (p = 0.01). Importantly, decreases in cerebral total hemoglobin (HbT), a measure of cerebral blood volume, did not correlate significantly with decreases in MAP. We conclude that 1) decreases in cerebral intravascular oxygenation, as assessed by NIRS, observed with decreases in MAP reflect a decline in CBF, and hence oxygen delivery, 2) the HbD signal is more sensitive to changes in CBF than the HbT signal, and 3) NIRS recordings may have clinical utility in detecting cerebral ischemia.


Pediatrics | 2005

A clinical decision rule to identify children at low risk for appendicitis

Anupam B. Kharbanda; George A. Taylor; Steven J. Fishman; Richard G. Bachur

Objective. Computed tomography (CT) has gained widespread acceptance in the evaluation of children with suspected appendicitis. Concern has been raised regarding the long-term effects of ionizing radiation. Other means of diagnosing appendicitis, such as clinical scores, are lacking in children. We sought to develop a clinical decision rule to predict which children with acute abdominal pain do not have appendicitis. Methods. Prospective cohort study was conducted of children and adolescents who aged 3 to 18 years, had signs and symptoms suspicious for appendicitis, and presented to the emergency department between April 2003 and July 2004. Standardized data-collection forms were completed on eligible patients. Two low-risk clinical decision rules were created and validated using logistic regression and recursive partitioning. The sensitivity, negative predictive value (NPV), and negative likelihood ratio of each clinical rule were compared. Results. A total of 601 patients were enrolled. Using logistic regression, we created a 6-part score that consisted of nausea (2 points), history of focal right lower quadrant pain (2 points), migration of pain (1 point), difficulty walking (1 point), rebound tenderness/pain with percussion (2 points), and absolute neutrophil count of >6.75 × 103/μL (6 points). A score ≤5 had a sensitivity of 96.3% (95% confidence interval [CI]: 87.5–99.0), NPV of 95.6% (95% CI: 90.8–99.0), and negative likelihood ratio of .102 (95% CI: 0.026–0.405) in the validation set. Using recursive partitioning, a second low-risk decision rule was developed consisting of absolute neutrophil count of <6.75 × 103/μL, absence of nausea, and absence of maximal tenderness in the right lower quadrant. This rule had a sensitivity of 98.1% (95% CI: 90.1–99.9), NPV of 97.5% (95% CI: 86.8–99.9), and negative likelihood ratio of 0.058 (95% CI: 0.008–0.411) in the validation set. Theoretical application of the low-risk rules would have resulted in a 20% reduction in CT. Conclusions. Our low-risk decision rules can predict accurately which children are at low risk for appendicitis and could be treated safely with careful observation rather than CT examination.


The American Journal of Clinical Nutrition | 2009

Relation of body fat indexes to vitamin D status and deficiency among obese adolescents

Carine Lenders; Henry A. Feldman; Emily von Scheven; Anne Merewood; Carol Sweeney; Darrell M. Wilson; Phillip D. K. Lee; Stephanie H. Abrams; Stephen E. Gitelman; Marcia Wertz; William J. Klish; George A. Taylor; Tai C. Chen; Michael F. Holick

BACKGROUND Data on the relation between vitamin D status and body fat indexes in adolescence are lacking. OBJECTIVE The objective was to identify factors associated with vitamin D status and deficiency in obese adolescents to further evaluate the relation of body fat indexes to vitamin D status and deficiency. DESIGN Data from 58 obese adolescents were obtained. Visceral adipose tissue (VAT) was measured by computed tomography. Dual-energy X-ray absorptiometry was used to measure total bone mineral content, bone mineral density, body fat mass (FM), and lean mass. Relative measures of body fat were calculated. Blood tests included measurements of 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), osteocalcin, type I collagen C-telopeptide, hormones, and metabolic factors. Vitamin D deficiency was defined as 25(OH)D < 20 ng/mL. PTH elevation was defined as PTH > 65 ng/mL. RESULTS The mean (+/-SD) age of the adolescents was 14.9 +/- 1.4 y; 38 (66%) were female, and 8 (14%) were black. The mean (+/-SD) body mass index (in kg/m(2)) was 36 +/- 5, FM was 40.0 +/- 5.5%, and VAT was 12.4 +/- 4.3%. Seventeen of the adolescents were vitamin D deficient, but none had elevated PTH concentrations. Bone mineral content and bone mineral density were within 2 SDs of national standards. In a multivariate analysis, 25(OH)D decreased by 0.46 +/- 0.22 ng/mL per 1% increment in FM (beta +/- SE, P = 0.05), whereas PTH decreased by 0.78 +/- 0.29 pg/mL per 1% increment in VAT (P = 0.01). CONCLUSIONS To the best of our knowledge, our results show for the first time that obese adolescents with 25(OH)D deficiency, but without elevated PTH concentrations, have a bone mass within the range of national standards (+/-2 SD). The findings provide initial evidence that the distribution of fat may be associated with vitamin D status, but this relation may be dependent on metabolic factors. This study was registered at www.clinicaltrials.gov as NCT00209482, NCT00120146.


Pediatrics | 1999

Effect of Computed Tomography on Patient Management and Costs in Children With Suspected Appendicitis

Barbara M. Garcia Peña; George A. Taylor; Dennis P. Lund; Kenneth D. Mandl

Objective. Children evaluated in the emergency department for possible appendicitis are often admitted for observation, despite the widespread availability of accurate diagnostic studies, particularly computed tomography (CT). We sought to establish effective and efficient strategies for using CT to diagnose and manage children with possible appendicitis. Design. Retrospective chart review and decision analysis. Setting. Emergency department of a large, urban tertiary care pediatric teaching hospital. Patients. All patients admitted from January 1996 to August 1997 for suspected appendicitis. Method of Analysis. Three modeled strategies were empirically applied to the retrospective cohort of patients admitted for observation. Outcomes and costs under the modeled strategies were compared with those under current practice. The three strategies were: 1) to obtain CT scans on all patients and discharge those with normal findings; 2) to obtain CT scans and admit all patients; 3) to selectively obtain CT scans on those patients with a peripheral white blood cell count >10 000/mm3 (10 × 109/L) and admit all. The sensitivity and specificity of CT for diagnosing appendicitis were determined empirically from the data. A sensitivity analysis was performed. Main Outcome Measures. The number of preoperative inpatient observation days, total hospital costs, and the rates of both missed appendicitis and negative laparotomies. Results. Of 609 patients hospitalized for possible appendicitis, 287 went directly to the operating room and 14 patients had known perforation and abscess. Three hundred eight children were observed and comprised the study cohort. Of the cohort, 112 (36.4%) underwent appendectomy and 26 (23.2%) of these had a normal appendix at pathology. Three patients were discharged from the hospital after observation and were subsequently readmitted with appendicitis (missed appendicitis). Among the 75 patients who had CT performed, the sensitivity and specificity of CT were both 97%. Under the current practice strategy, the cohort collectively accumulated 487 inpatient observation days and incurred a per patient cost of


Pediatrics | 2000

Costs and effectiveness of ultrasonography and limited computed tomography for diagnosing appendicitis in children.

Barbara M. Garcia Peña; George A. Taylor; Steven J. Fishman; Kenneth D. Mandl

5831. All three CT strategies would have reduced the total number of inpatient observation days, operations, negative laparotomies, as well as the per patient cost. The strategy of obtaining CT scans on all patients and then admitting them had the lowest rate of missed appendicitis. The additional cost of preventing each case of missed appendicitis under this strategy compared with the strategy of obtaining CT scans and sending home those with negative findings was


American Journal of Pathology | 2004

Early Adaptive Responses of the Vascular Wall during Venous Arterialization in Mice

Stephanie Kwei; George Stavrakis; Masaya Takahas; George A. Taylor; M.Judah Folkman; Michael A. Gimbrone; Guillermo García-Cardeña

150 304. Even at the lowest reported sensitivity and specificity of CT in the literature, the ordering of the three strategies remained constant and continued to reduce total cost per patient. Conclusion. Compared with current practice, diagnostic strategies using CT could reduce costs and improve diagnosis, management, and outcomes for children with appendicitis.


Pediatric Research | 2000

Noninvasive detection of changes in cerebral blood flow by near-infrared spectroscopy in a piglet model of hydrocephalus.

Janet S. Soul; George A. Taylor; David Wypij; Adre J duPlessis; Joseph J. Volpe

Background. A protocol of ultrasonography (US) followed by computed tomography with rectal contrast (CTRC) has been shown to be 94% accurate in the diagnosis of acute appendicitis in children. Objective. To evaluate the changes in patient management and costs of a protocol using US and CTRC in the evaluation of appendicitis in children. Design, Setting, and Subjects. Prospective cohort study of 139 children between 3 and 21 years of age who had equivocal clinical findings for acute appendicitis seen in the emergency department of a large, urban pediatric teaching hospital between July 1998 and December 1998. Protocol. Children with equivocal clinical presentations for acute appendicitis were prospectively evaluated with US. Patients with positive findings for acute appendicitis went directly to the operating room. Patients with negative or equivocal findings on US underwent CTRC. Surgical management plans were recorded before imaging, after US, and after CTRC. Main Outcome Measures. Surgical management plans before and after the imaging protocol as well as total hospital direct and indirect costs incurred or saved by each change in management were determined. Costs were obtained through the hospitals cost database and by ratios of costs to charges. Results. Of the 139 children, the protocol resulted in a beneficial change in management in 86 children (61.9%), no change in management in 50 children (36.0%) and an incorrect change in management in 3 children (2.1%). US alone resulted in a beneficial change in management decision in 12/31 children (38.7%), while US followed by CTRC resulted in a beneficial change in management in 74/108 children (68.5%). The protocol resulted in a total cost savings of


Radiology | 2008

Pediatric radiation exposure and effective dose reduction during voiding cystourethrography.

Valerie L. Ward; Keith J. Strauss; Carol E. Barnewolt; David Zurakowski; Vaidehi Venkatakrishnan; Frederic H. Fahey; Robert L. Lebowitz; George A. Taylor

78 503.99 or

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Carlos J. Sivit

Case Western Reserve University

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Martin R. Eichelberger

Children's Hospital of Philadelphia

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Billie L. Short

George Washington University

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Patricia Dunning

Boston Children's Hospital

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David Zurakowski

Boston Children's Hospital

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D I Bulas

Uniformed Services University of the Health Sciences

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Catherine S. Gotschall

Children's National Medical Center

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