BioMedical Computer Research Institute

Philadelphia, PA, United States

BioMedical Computer Research Institute

Philadelphia, PA, United States
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Ross J.L.,Thomas Jefferson University | Ross J.L.,DuPont Company | Kushner H.,Biomedical Computer Research Institute | Zinn A.R.,University of Texas Southwestern Medical Center | And 5 more authors.
Pediatrics | Year: 2012

OBJECTIVE: To contrast the behavioral and social phenotypes including a screen for autistic behaviors in boys with 47,XYY syndrome (XYY) or 47,XXY Klinefelter syndrome (KS) and controls and investigate the effect of prenatal diagnosis on the phenotype. METHODS: Patients included 26 boys with 47,XYY, 82 boys with KS, and 50 control boys (ages 4-15 years). Participants and parents completed a physical examination, behavioral questionnaires, and intellectual assessments. RESULTS: Most boys with XYY or KS had Child Behavior Checklist parental ratings within the normal range. On the Child Behavior Checklist, mean problem behaviors t scores were higher in the XYY versus KS groups for the Problem Behavior, Externalizing, Withdrawn, Thought Problems, and Attention Problems subscales. On the Conners' Parent Rating Scale-Revised, the XYY versus KS group had increased frequency of hyperactive/impulsive symptoms (P < .006). In addition, 50% and 12% of the XYY and KS groups, respectively, had scores >15 for autism screening from the Social Communication Questionnaire. For the boys with KS, prenatal diagnosis was associated with fewer problem behaviors. CONCLUSIONS: A subset of the XYY and KS groups had behavioral difficulties that were more severe in the XYY group. These findings could guide clinical practice and inform patients and parents. Boys diagnosed with XYY or KS should receive a comprehensive psychoeducational evaluation and be screened for learning disabilities, attention-deficit/hyperactivity disorder, and autism spectrum disorders. Copyright © 2012 by the American Academy of Pediatrics.

Lee L.H.,University of California at San Francisco | Jun J.H.,University of California at San Francisco | Danganan M.,University of California at Los Angeles | Pogrel M.A.,University of California at San Francisco | And 2 more authors.
International Journal of Oral and Maxillofacial Surgery | Year: 2011

The aim of this study was to determine whether there are differences in esthetic preferences and orthognathic treatment for Asian patients between US- and Asian-trained surgeons. Twenty-five Caucasian-American, 23 Asian-American, 24 Asian oral and maxillofacial surgeons (OMFS) completed an Institutional Review Board (IRB)-approved survey. They were asked to rate seven Asian male and female profiles from most attractive to least attractive and to choose maxillary advancement, mandibular setback, or no treatment for an Asian male and female patient with a maxillomandibular discrepancy. There was no statistical difference for the most and least attractive rankings among the OMFS. Variations in ranking for intermediate profiles showed a statistical difference between the Asian- and US-trained OMFS. These intermediate profile rankings appeared to explain the differences in surgical treatment. Treatment recommendations for the Asian male among the OMFS, regardless of ethnicity, preferred maxillary advancement. For the Asian female, all Asian-trained OMFS preferred mandibular setback, while nearly 40% of US-trained OMFS preferred maxillary advancement (p = 0.003). Differences in surgical management of the Asian patient were dependent on whether the surgeon trained in the US or in Asia and the gender of the patient. There was concordance between the Asian-American and Caucasian-American surgeons. © 2010 International Association of Oral and Maxillofacial Surgeons.

Ogbureke K.U.E.,Georgia Regents University | Abdelsayed R.A.,Georgia Regents University | Kushner H.,BioMedical Computer Research Institute | Li L.,U.S. National Institutes of Health | Fisher L.W.,U.S. National Institutes of Health
Cancer | Year: 2010

BACKGROUND: Patients with oral premalignant lesions (OPL) present with oral squamous cell carcinomas (OSCC) at a much higher rate than the general population. There are currently no useful markers that indicate specifically which OPLs are most likely to progress. Three small integrin binding ligands N-linked glycoprotein (SIBLING) family proteins, bone sialoprotein (BSP), osteopontin (OPN), and dentin sialophosphoprotein (DSPP), have been shown to be upregulated in many cancers, including OSCC. The status of SIBLING expression in OPLs and their correlation to transition to oral cancer are unknown. METHODS: Sixty archival surgical biopsies of dysplastic OPLs were evaluated by immunohistochemistry for expression of BSP, DSPP, and OPN and correlated with local transformation to OSCC at sites adjacent to surgically removed dysplastic OPL. RESULTS: The OPL patient population was representative of previous studies with 20% progressing to OSCC, and no correlation between degree of dysplasia and progression. Eighty-seven percent were positive for at least 1 SIBLING protein. OPN expression had no correlation with progression. The BSP+/DSPP- expression pattern however correlated with decreased transformation to OSCC (point prevalence = 0%; 95% confidence interval [CI], 0-20.6), whereas the BSP-/DSPP+ pattern was associated with more frequent progression (point prevalence = 77.8%; 95%CI, 47.8-95.4). Incrementally higher expression scores (0 to 3) of BSP and DSPP were also associated with increased predictive values (odds ratio, 25.53; 95% CI, 2.14-304.7 and 10.13; 95% CI, 2.0-50.0, respectively, for each increment). CONCLUSIONS: BSP and DSPP are excellent candidate markers for successful OPL surgical intervention and may be predictors of OPL-OSCC progression. © 2010 American Cancer Society.

PubMed | National Health Research Institute, University of California at San Francisco and Biomedical Computer Research Institute
Type: Comparative Study | Journal: Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons | Year: 2015

To examine and compare the skeletal and dental effects of surgically assisted rapid palatal expansion (SARPE) and multipiece Le Fort osteotomy using cone-beam computed tomography (CBCT).This was a prospective cohort study. Patients underwent SARPE or multipiece Le Fort I osteotomy to address maxillary transverse deficiency. CBCT scans were taken preoperatively, immediately postoperatively or after retention, and at least 6 months postoperatively. Four landmark measurements and ratios of dental-to-skeletal change were used to follow skeletal and dental widths in the posterior and anterior maxillary regions. Wilcoxon signed-rank test and Wilcoxon 2-sample rank-sum test were used to compare the landmark measurements and the ratio of dental-to-skeletal change for the 2 surgeries. A P value less than .05 was statistically significant.Thirteen patients (mean, 28.3 yr old; 7 women) were enrolled: 9 were treated by multipiece Le Fort I osteotomy and 4 were treated by SARPE. The ratios of dental-to-skeletal expansion in the posterior maxilla for the Le Fort procedure and SARPE were 0.70 0.41 and 25.20 15.8, respectively, and the dental-to-skeletal relapses were 1.17 0.80 and -3.63 3.70, respectively. The ratios of dental-to-skeletal expansion in the anterior maxilla for the Le Fort procedure and SARPE were 0.58 0.38 and 31.80 59.4, respectively, and the dental-to-skeletal relapses were 2.25 3.41 and 4.86 8.10, respectively.There was greater correlation between dental and skeletal changes in the multipiece Le Fort procedure, indicating bodily separation of the segments, whereas the SARPE showed noteworthy dental and skeletal tipping. Dental relapse was greater than skeletal relapse for these 2 procedures.

PubMed | National Health Research Institute, University of California at San Francisco and Biomedical Computer Research Institute
Type: Comparative Study | Journal: Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons | Year: 2015

Orthognathic surgery can induce changes in airway volume. The aim of this study was to determine whether there is a correlation of surgical movement of the maxilla or mandible to airway volume changes.This was a prospective cohort study and the sample was composed of patients undergoing single-jaw orthognathic procedures from 2004 through 2007. Cone-beam computed tomograms were obtained before surgery (T0), immediately after surgery (T1), and at least 6months after surgery (T2). The airway was segmented from 3-dimensional images and identified as the whole airway, consisting of the naso-, oro-, and hypopharynx. The volumetric percentage of change of the airway between time points was compared and correlated to the surgical movements using paired t test and cubic regression analysis. The level of statistical significance was set at a P value less than or equal to .05.The sample was composed of 33 patients. Sixteen patients underwent maxillary advancement with mean advancement of 5.4mm (3 to 8mm), 13 underwent mandibular advancement with mean advancement of 8.0mm (5 to 15mm), and 4 underwent mandibular setback of 4.0mm. For maxillary advancement at T1, volume percentages of change for the whole airway and the naso-, oro-, and hypopharynx were 18.4 (P .05), 53.8 (P .05), 26.3, and 5.5%, respectively, and at T2, the changes were 10.0, 46.7(P .05), 6.8, and 1.0%, respectively. For mandibular advancement at T1, volume percentages of change were 34.6 (P .05), 26.1, 54.1 (P .05), and 17.4%, respectively, and at T2, the changes were 15.0 (P .05), -3.7, 23.5 (P .05), and 12.1%, respectively. There were no meaningful long-term airway changes with mandibular setback.The study results suggest that there might be an anatomic limit to pharyngeal airway expansion associated with single-jaw orthognathic surgery.

Zeger M.P.D.,Thomas Jefferson University | Zeger M.P.D.,DuPont Company | Shah K.,Thomas Jefferson University | Kowal K.,Thomas Jefferson University | And 4 more authors.
Hormone Research in Paediatrics | Year: 2011

Background/Aims: Untreated girls with Turner syndrome (TS) have growth failure, and adult height is, on average, 20 cm less than predicted height. Treatment with growth hormone (GH) is now standard of care. The objective of this study was to investigate the benefit of adding oxandrolone (Ox) to GH in a long-term, randomized, placebo (Pl)-controlled prospective trial to near adult height in TS. Methods: Prospective, randomized, Pl-controlled study: 76 girls with TS (ages 10-14.9 years) were randomized to receive Ox (0.06 mg/kg/day) or Pl in combination with GH (0.35 mg/kg/week, daily) over 2 years. Auxologic data, breast and pubic hair Tanner stages, and hormone and lipid levels were measured. Subjects who chose to continue were followed in a 2-year double-blind extension, also received estrogen therapy (years 3, 4), and had dual-energy X-ray absorptiometry evaluation of bone density (years 3, 4). Results: At year 4, the change in absolute height and height SDS was greater in the GH/Ox versus GH/Pl group [26.2 ± 6.7 vs. 22.2 ± 5.1 cm, analysis of covariance (ANCOVA) p < 0.001; 1.8 ± 0.9 vs. 1.2 ± 0.7 standard deviation scores, ANCOVA p < 0.001]. Bone mineral density (BMD) of the wrist (0.51 ± 0.17 vs. 0.54 ± 0.05 g/cm2) and spine (0.91 ± 0.34 vs. 0.96 ± 0.13 g/cm2) in the GH/Ox versus GH/Pl groups was similar after 4 years. Breast development was slower in the GH/Ox versus GH/Pl group [year 4: Tanner stage 2.9 ±1.3 (Ox) vs. 4.1 ± 1.3 (Pl), p = 0.003], and menarche was approximately 1 year later. Conclusions: The addition of Ox to GH at mean age 12.0 ± 1.7 year augmented height gain after 4 years of treatment, slowed breast development and did not affect BMD in girls with TS. Whether initiation of Ox prior to initiation of pubertal development would optimize height gain without impeding breast development will require further study. Copyright © 2010 S. Karger AG, Basel.

PubMed | Johns Hopkins University, Corcept Therapeutics, BioMedical Computer Research Institute and University of Alabama at Birmingham
Type: | Journal: BMC endocrine disorders | Year: 2015

Overweight and obesity are common among patients with Cushings syndrome (CS) and may persist in some patients even after ostensibly curative surgery, contributing to cardiometabolic dysfunction and increased cardiovascular risk. Mifepristone, a selective glucocorticoid receptor antagonist, was effective in controlling hyperglycemia in a 24-week trial of adults (N = 50) with endogenous CS and associated type 2 diabetes mellitus/impaired glucose tolerance or hypertension who had failed or were not candidates for surgery (SEISMIC, Study of the Efficacy and Safety of Mifepristone in the Treatment of Endogenous Cushings Syndrome). This analysis examines long-term weight change among patients who received mifepristone in SEISMIC and enrolled in a long-term safety extension (LTE) study.Patients completing the 24-week SEISMIC study and subsequent 6-week off-drug safety evaluation were invited to enroll in the LTE study. Mifepristone doses at the end of SEISMIC were the LTE starting doses. Body weight measures were reviewed at baseline and week 24 of SEISMIC and at LTE month 6, 12, 18, 24, and final visit (last observation collected during the LTE study).Of the 30 patients enrolled in the LTE, evaluable weight data were available for 29 (20/29 female; mean age of 44.7 11.2 years). These patients received mifepristone for a median of 29.2 months (range 8.4-41.9). Mean SD weight from SEISMIC baseline to LTE final visit decreased by 10.3 16.3 kg (mean 105.4 34.3 kg to 95.1 32.9 kg), a 9.3 % decrease from baseline weight (P = 0.0008). Of the 29 LTE patients, 18 (62.1 %) lost 5 % of body weight by the end of the initial 24-week treatment period; this 5 % weight loss persisted in 83.3 % (15/18) at LTE final visit. Ten patients (34.5 %) lost 10 % of initial body weight by week 24 of SEISMIC, which persisted in 80 % at LTE final visit. No new safety signals were detected with long-term mifepristone use.Clinically meaningful weight loss achieved during a 24-week study of mifepristone for CS persisted for two additional years in patients who remained on therapy. Long-term treatment with mifepristone appears to have a beneficial effect on weight in patients with endogenous CS.NCT00569582 (SEISMIC); NCT00936741 (Long-Term Extension).

PubMed | Independent Pharmacokinetics Consultant, Inc formerly Columbia Laboratories, BioMedical Computer Research Institute and ABC Laboratories
Type: | Journal: Clinical pharmacology in drug development | Year: 2016

Lidocaine vaginal bioadhesive gel is being developed as a local anesthetic for use in minimally invasive outpatient gynecological procedures and was investigated in single-dose and multiple-dose studies in healthy young adult women. Lidocaine doses of 2.5%, 5%, and 10% (w/w) were administered, and parent drug and metabolites monoethylglycinexylidide and glycinexylidide were measured in plasma. Lidocaine was absorbed through vaginal tissue and into the systemic circulation in a dose-proportional manner, and there was little systemic accumulation. Plasma concentrations were 10- to 20-fold lower than concentrations obtained after administration of intravenous lidocaine used to treat arrhythmic activity, thus demonstrating a wide safety margin for a vaginal lidocaine product.

PubMed | National Health Research Institute, Johns Hopkins University, Tel Aviv University, Deceased. and Biomedical Computer Research Institute
Type: Journal Article | Journal: The Journal of bone and joint surgery. American volume | Year: 2016

Polyostotic fibrous dysplasia is a skeletal disease that results from somatic activating mutations in the gene GNAS in skeletal stem cells, leading to proliferation of immature osteogenic cells with replacement of normal marrow and bone with fibro-osseous tissue. Lesions may cause bone deformity or fracture. In the surgical care of polyostotic fibrous dysplasia, the role of grafting and the optimal grafting material are not clear. The purpose of this study was to evaluate the long-term survival of bone-grafting procedures in subjects with polyostotic fibrous dysplasia over time.The operative reports and radiographs of a cohort of subjects with polyostotic fibrous dysplasia followed in a natural history study were reviewed. Twenty-three subjects (mean age at the time of enrollment, thirteen years [range, two to forty years]) with fifty-two bone-grafting procedures had a mean follow-up time of 19.6 years (range, twenty-nine months to forty-seven years). Kaplan-Meier life table estimates, Cox proportional hazard models, and t tests comparing means were performed to assess various aspects of graft survival.Kaplan-Meier curves showed a 50% estimate of survival of 14.5 years. Cox proportional hazards models showed no advantage comparing allograft with autograft or structural with nonstructural graft materials. The mean age of the patients was significantly greater (p < 0.001) in the subgroup of subjects in whom grafts were maintained over time (20.9 years) compared with the subgroup of patients whose grafts were resorbed over time (9.8 years).Bone-grafting, including both allograft and autograft, is of limited value in ablating the lesions of fibrous dysplasia. The expectations of patients and surgeons should include the high probability of graft resorption over time with return of bone characteristics of fibrous dysplasia, particularly in younger patients. This suggests the maintenance of normal bone mechanics with implant support should be the priority of any surgical intervention.

Boyce A.M.,U.S. National Institutes of Health | Boyce A.M.,Childrens National Health System | Boyce A.M.,Bone Health Program | Kelly M.H.,U.S. National Institutes of Health | And 7 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2014

Context: Fibrous dysplasia (FD) is a rare skeletal disorder, resulting in deformity, fracture, functional impairment, and pain. Bisphosphonates have been advocated as a potential treatment.Objective: To determine the efficacy of alendronate for treatment of FD.Design: Two-year randomized, double-blind, placebo-controlled trial.Setting: Clinical research center.Patients: Forty subjects with polyostotic FD (24 adults, 16 children). Subjects were randomized and stratified by age.Interventions: Study drug was administered over a 24 month period in 6 month cycles (6 months on, 6 months off). Alendronate dosing was stratified: 40 mg daily for subjects > 50 kg, 20 mg for 30-50 kg, 10 mg for 20-30 kg.Main Outcome Measures: Primary endpoints were bone turnover markers, including serum osteocalcin, and urinary NTX-telopeptides. Secondary endpoints included areal bone mineral density (aBMD), pain, skeletal disease burden score, and functional parameters including the 9-min walk test and manual muscle testing.Results: Clinical data was collected on 35 subjects who completed the study. There was a decline in NTX-telopeptides in the alendronate group (P = .006), but no significant difference in osteocalcin between groups. The alendronate group had an increase in areal BMD in normal bone at the lumbar spine (P =.006), and in predetermined regions of FD (P<.001). There were no significant differences in pain scores, skeletal disease burden scores, or functional parameters between the groups.Conclusions: Alendronate treatment led to a reduction in the bone resorption marker NTX-telopeptides, and improvement in aBMD, but no significant effect on serum osteocalcin, pain, or functional parameters. Copyright © 2014 by the Endocrine Society.

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