Joel Finkelstein | Princeton University (original) (raw)
Papers by Joel Finkelstein
Nature, 2015
Anxiety-related conditions are among the most difficult neuropsychiatric diseases to treat pharma... more Anxiety-related conditions are among the most difficult neuropsychiatric diseases to treat pharmacologically, but respond to cognitive therapies. There has therefore been interest in identifying relevant top-down pathways from cognitive control regions in medial prefrontal cortex (mPFC). Identification of such pathways could contribute to our understanding of the cognitive regulation of affect, and provide pathways for intervention. Previous studies have suggested that dorsal and ventral mPFC subregions exert opposing effects on fear, as do subregions of other structures. However, precise causal targets for top-down connections among these diverse possibilities have not been established. Here we show that the basomedial amygdala (BMA) represents the major target of ventral mPFC in amygdala in mice. Moreover, BMA neurons differentiate safe and aversive environments, and BMA activation decreases fear-related freezing and high-anxiety states. Lastly, we show that the ventral mPFC-BMA projection implements topdown control of anxiety state and learned freezing, both at baseline and in stress-induced anxiety, defining a broadly relevant new top-down behavioural regulation pathway. Reprints and permissions information is available at www.nature.com/reprints.
Cell, 2014
Social interaction is a complex behavior essential for many species and is impaired in major neur... more Social interaction is a complex behavior essential for many species and is impaired in major neuropsychiatric disorders. Pharmacological studies have implicated certain neurotransmitter systems in social behavior, but circuit-level understanding of endogenous neural activity during social interaction is lacking. We therefore developed and applied a new methodology, termed fiber photometry, to optically record natural neural activity in genetically and connectivity-defined projections to elucidate the realtime role of specified pathways in mammalian behavior. Fiber photometry revealed that activity dynamics of a ventral tegmental area (VTA)-tonucleus accumbens (NAc) projection could encode and predict key features of social, but not novel object, interaction. Consistent with this observation, optogenetic control of cells specifically contributing to this projection was sufficient to modulate social behavior, which was mediated by type 1 dopamine receptor signaling downstream in the NAc. Direct observation of deep projection-specific activity in this way captures a fundamental and previously inaccessible dimension of mammalian circuit dynamics. (A) (Left) Photometry setup. Light path for fluorescence excitation and emission is through a single 400 mm fiber optic implanted in VTA. (Right) Viral targeting of GCaMP5 to VTA-DA neurons.
Objective and Context:Our objective was to examine predictability of reproductive hormone concent... more Objective and Context:Our objective was to examine predictability of reproductive hormone concentrations for bone mineral density (BMD) loss during the menopausal transition. Design: We conducted a longitudinal (five annual examinations), multiple-site (n 5) cohort study, the Study of Women's Health Across the Nation (SWAN). Participants: Participants included, at baseline, 2311 premeno- pausal or early perimenopausal African-American, Caucasian, Chi- nese, and
The Journal of Trauma: Injury, Infection, and Critical Care, 1996
The American journal of clinical nutrition, Jan 8, 2015
Epidemiologic data suggest that low serum 25-hydroxyvitamin D [25(OH)D] increases insulin resista... more Epidemiologic data suggest that low serum 25-hydroxyvitamin D [25(OH)D] increases insulin resistance and the risk of type 2 diabetes. Few interventional trials have assessed the effect of vitamin D on insulin metabolism, and published results are discordant. The goal of this study was to perform a detailed assessment of the effect of ergocalciferol administration on glucose and insulin metabolism in healthy people with low total 25(OH)Dtotal. This was a 12-wk, double-blinded, randomized controlled trial. We enrolled 90 healthy volunteers aged 18-45 y with serum 25(OH)D ≤20 ng/mL (by immunoassay) and administered ergocalciferol 50,000 IU/wk or placebo for 12 wk. Primary endpoints were change in first-phase insulin response and insulin sensitivity as measured by intravenous glucose tolerance test. Secondary endpoints included change in homeostasis model assessment of insulin resistance; fasting glucose, insulin, and lipids; body mass index (BMI); and blood pressure. On-study 25(OH)Dto...
CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne, Jan 6, 2015
Older people are at increased risk of traumatic spinal cord injury from falls. We evaluated the i... more Older people are at increased risk of traumatic spinal cord injury from falls. We evaluated the impact of older age (= 70 yr) on treatment decisions and outcomes. We identified patients with traumatic spinal cord injury for whom consent and detailed data were available from among patients recruited (2004-2013) at any of the 31 acute care and rehabilitation hospitals participating in the Rick Hansen Spinal Cord Injury Registry. Patients were assessed by age group (< 70 v. ≥ 70 yr). The primary outcome was the rate of acute surgical treatment. We used bivariate and multivariate regression models to assess patient and injury-related factors associated with receiving surgical treatment and with the timing of surgery after arrival to a participating centre. Of the 1440 patients included in our study cohort, 167 (11.6%) were 70 years or older at the time of injury. Older patients were more likely than younger patients to be injured by falling (83.1% v. 37.4%; p < 0.001), to have a c...
NMR in Biomedicine, 2015
Quantitative T2 (qT2), diffusion tensor imaging (DTI), and histology were used to investigate a c... more Quantitative T2 (qT2), diffusion tensor imaging (DTI), and histology were used to investigate a cervical model of spinal cord injury (SCI) in the rat. While quantitative MRI can significantly increase the specificity in the presence of pathology, it must be validated for each type of injury or disease. In the case of traumatic SCI most models are difficult to image, either due to the location of the injury, or as a result of damage to surrounding tissues resulting from invasive surgical procedures. In this study a non-surgical cervical model of SCI, produced using a combination of focused ultrasound and microbubbles, was used to produce pathology similar to that seen in models of contusive and compressive injuries. qT2 and DTI were performed at 24 h and 1 and 2 weeks following injury, and compared with H&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;E and luxol fast blue histology. In the injured spinal cord, in addition to intra/extracellular (I/E) water and myelin water in white matter, qT2 revealed a large component with very short T2 of about 3 ms, which was highly correlated with the presence of hemorrhage in both gray and white matter at 24 h, and with the presence of hemosiderin in gray matter at 2 weeks following injury. The T2 of the I/E water peak was also elevated at 24 h in both gray and white matter, which was correlated with the presence of vacuolation/edema on histology. Cystic cavities were only seen at the 1 or 2 week timepoints, and were correlated with the presence of a water peak with T2 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 250 ms. No significant changes in diffusivity parameters were observed. Pathologies were often co-occurring, with opposite effects on the average T2 in a given voxel, reducing the visibility of injured tissue on standard T2 -weighted MR images. Copyright © 2015 John Wiley &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp; Sons, Ltd.
Current Orthopaedic Practice, 2011
ABSTRACT Background: The goal of this study was to evaluate a new second generation of computer-a... more ABSTRACT Background: The goal of this study was to evaluate a new second generation of computer-assisted fluoroscopic navigation software for fracture reduction (SGFR) of long-bone fractures. The new software allows simultaneous tracking of two moving bone fragments. Methods: Between 2005–2007, patients with isolated, extra-articular long-bone fracture of either the femur or tibia were considered for computer-assisted fluoroscopic fracture reduction surgery. The operative tasks were: (1) fracture reduction; (2) determination of the entry point, and; (3) Poller screw insertion, when needed. Fracture reduction was achieved by one of two methods: (1) fracture edges or (2) medullary canal recognition. Fracture reduction was considered successful if the guide wire was introduced through the fracture without further radiation. Results: We treated 38 patients (27 men and 11 women); with 15 femoral and 23 tibial fractures, with intramedullary nail fixation. In all patients, the point of entry was navigated successfully. In four patients, the insertion of the blocking screw was planned and executed without further radiation. All fractures were successfully reduced using the SGFR system. In nine patients, we used method 1, in 22 patients method 2, and in six a combination of both. The number of fluoroscopic images was dramatically reduced to four to six images. Conclusions: Fracture reduction was reliably achievable in all patients using the SGFR. A key conclusion is that only a small number of fluoroscopic images are required. Although timing was not an objective of this study, we believe that there was a noticeable reduction of intraoperative time.
Cell, 2014
Social interaction is a complex behavior essential for many species and is impaired in major neur... more Social interaction is a complex behavior essential for many species and is impaired in major neuropsychiatric disorders. Pharmacological studies have implicated certain neurotransmitter systems in social behavior, but circuit-level understanding of endogenous neural activity during social interaction is lacking. We therefore developed and applied a new methodology, termed fiber photometry, to optically record natural neural activity in genetically and connectivity-defined projections to elucidate the real-time role of specified pathways in mammalian behavior. Fiber photometry revealed that activity dynamics of a ventral tegmental area (VTA)-to-nucleus accumbens (NAc) projection could encode and predict key features of social, but not novel object, interaction. Consistent with this observation, optogenetic control of cells specifically contributing to this projection was sufficient to modulate social behavior, which was mediated by type 1 dopamine receptor signaling downstream in the NAc. Direct observation of deep projection-specific activity in this way captures a fundamental and previously inaccessible dimension of mammalian circuit dynamics.
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, Jan 16, 2015
Improvements in clinical care have led to increased life expectancy in patients with cystic fibro... more Improvements in clinical care have led to increased life expectancy in patients with cystic fibrosis (CF) over the past several decades. Whether these improvements have had significant effects on bone health in patients with CF is unclear. This is a cross-sectional study comparing clinical characteristics and bone mineral density (BMD) measured by dual energy X-ray absorptiometry (DXA) in adults with CF evaluated in 1995-1999 to age-, race-, and gender-matched patients with CF evaluated in 2011-2013 at the same center on calibrated DXA machines. The cohorts were similar in terms of age, BMI, pancreatic insufficiency, presence of F508del mutation, and reproductive history. In the most recent cohort, pulmonary function was superior, and fewer patients had vitamin D deficiency or secondary hyperparathyroidism. Areal BMD measures of the PA spine, lateral spine, and distal radius were similarly low in the two cohorts. Although pulmonary function and vitamin D status were better in patien...
Journal of Spinal Disorders, 1999
A prospective cohort study of consecutive patients with thoracolumbar fractures from two centers ... more A prospective cohort study of consecutive patients with thoracolumbar fractures from two centers was conducted to evaluate the use of cortical allograft for anterior spine reconstruction. The purpose was to determine whether allograft bone had deleterious effects on fusion rates and maintenance of correction. Thirty-six patients were followed for a minimum of 2 years. A radiologic fusion rate of 81% was found, and there was a loss of postoperative correction in eight patients. The addition of posterior instrumentation was not significantly different from anterior surgery alone with respect to union rates but did provide a more reliable maintenance of correction of deformity. There were no cases of disease transmission. The authors conclude that cortical allograft for anterior spine reconstruction in trauma is safe and despite having a fusion rate lower than autogenous iliac crest, little clinical significance is attributable to the radiologic appearance of nonunion at the host-allograft junctions.
Long-term compliance with pharmacologic treatments for many asymptomatic conditions may be subopt... more Long-term compliance with pharmacologic treatments for many asymptomatic conditions may be suboptimal, but little is known about compliance with medications used for osteoporosis. This study was undertaken to assess the level and determinants of compliance with drugs prescribed for osteoporosis. This retrospective cohort study used pharmacy claims data from US Medicare and filled prescriptions from a state pharmaceutical benefits program. We included persons 65 years or older who initiated use of a medication for osteoporosis (alendronate sodium, calcitonin, hormone therapy, raloxifene hydrochloride, or risedronate) from January 1, 1996, through December 31, 2002. The outcome of interest was suboptimal medication compliance, defined as equal to or less than 66% of days with medication during a 60-day period. One year after initiating treatment for osteoporosis, 45.2% of the 40,002 patients were not continuing to fill prescriptions. Five years after initiation, 52.1% of patients were not continuing to fill prescriptions for an osteoporosis medication. Several characteristics independently predicted compliance: female sex, younger age, fewer comorbid conditions, using fewer nonosteoporosis medications, bone mineral density testing before and after initiating a medication, a fracture before and after initiating a medication, and nursing home residence during the 12 months before initiating a medication. However, models adjusted for the significant patient variables explained only 6% of the variation in compliance. Most patients who initiate a medication for osteoporosis do not continue to take it as prescribed. Although several patient characteristics significantly correlated with compliance, adjusted models explained little of the variation.
Cancer Metastasis – Biology and Treatment, 2009
Orthopaedic and spinal surgery can provide significant palliation to patients with symptoms arisi... more Orthopaedic and spinal surgery can provide significant palliation to patients with symptoms arising for bony metastatic involvement in addition to patients that are at risk for skeletally related events (SREs). This chapter will review the role of surgery in the management of bone metastases and discuss factors that need to be considered prior to surgery. The treatment of pathologic fractures
Annals of Vascular Surgery, 1993
This case presentation reports the second case of axillary artery thrombosis secondary to pectora... more This case presentation reports the second case of axillary artery thrombosis secondary to pectoralis minor compression. Evidence to explain this etiology is presented from arteriographic and intraoperative clinical findings. Management includes division of the pectoralis minor muscle and local arterial repair if the vessel is severely damaged. (Ann Vasc Surg 1993;7:287-290.) In the spectrum of thoracic outlet syndrome, arterial compression occurs in less than 5 % of all patients. ~ Compression of the subclavian artery is primarily in the costoscalene passage where bony abnormalities, including cervical ribs and fibrous bands, have been recognized. 2 Less frequently, compression may occur at the costoclavicular space. ~ The importance of the .hyperabduction syndrome and the pectoralis minor tendon as a cause of axillary artery compression has also been well described. 4-6 However, to our knowledge, only one case of axillary artery thrombosis secondary to pectoralis minor compression has been reported. ~ We report a case of axillary artery thrombosis secondary to compression by the pectoralis minor with thromboembolism occluding the radial and ulnar arteries.
International Quarterly of Community Health Education, 2008
Objective-To better understand high-risk patients' readiness to engage in bone mineral density (B... more Objective-To better understand high-risk patients' readiness to engage in bone mineral density (BMD) testing to diagnose osteoporosis.
Mayo Clinic Proceedings, 2005
To assess current osteoporosis treatment guidelines, studies of osteoporosis treatment, and inter... more To assess current osteoporosis treatment guidelines, studies of osteoporosis treatment, and interventions to improve osteoporosis treatment. We searched the medical literature for articles published between January 1, 1992, and December 31, 2003, and assessed all relevant articles using a structured data abstraction process. Because of substantial heterogeneity in study design, no attempt was made to summarize the data using meta-analytic techniques. Seventy-six articles met criteria for inclusion. Eighteen practice guidelines were studied. Most guidelines were consistent in key treatment recommendations. Among 18 studies of treatment rates in patients who had fractures, the weighted average varied from 22% for nonhormonal treatment to 19% for calcium. We found slightly higher treatment rates for patients taking oral glucocorticoids or for those older than 65 years. There were no consistent correlates of which patients received treatment. Six studies that examined treatment frequencies after bone densitometry all found that patients with lower bone mineral density were more likely to receive treatment. Most of the 8 interventions designed to improve osteoporosis treatment showed improvement in treatment rates; however, only 3 were randomized, and these showed the smallest effects. Frequency of treatment of osteoporosis in at-risk populations is low. However, our assessment of the literature revealed no clear and consistent predictors of undertreatment. Few carefully controlled interventions have been reported.
The Spine Journal, 2010
ABSTRACT Decompression alone (D) is a well-accepted treatment for patients with lumbar spinal ste... more ABSTRACT Decompression alone (D) is a well-accepted treatment for patients with lumbar spinal stenosis (LSS) causing neurogenic claudication; however, D is controversial in patients with LSS who have degenerative spondylolisthesis (DLS). Our goal was to compare the outcome of anatomy-preserving D with decompression and fusion (DF) for patients with grade I DLS. We compared patients with DLS who had elective primary 1-2 level spinal D at 1 centre with a cohort who had 1-2 level spinal DF at 5 other centres.
The Spine Journal, 2011
The results of single-center studies have shown that surgical intervention for lumbar spinal sten... more The results of single-center studies have shown that surgical intervention for lumbar spinal stenosis yielded comparable health-related quality of life (HRQoL) improvement to total joint arthroplasty (TJA). Whether these results are generalizable to routine clinical practice in Canada is unknown. The primary purpose of this equivalence study was to compare the relative improvement in physical HRQoL after surgery for focal lumbar spinal stenosis (FLSS) compared with TJA for hip and knee osteoarthritis (OA) across six Canadian centers. A Canadian multicenter ambispective cohort study. A cohort of 371 primary one- to two-level spinal decompression (n=214 with instrumented fusion) for FLSS (n=179 with degenerative lumbar spondylolisthesis [DLS]) was compared with a cohort of primary total hip (n=156) and knee (n=208) arthroplasty for OA. The primary outcome was the change in preoperative to 2-year postoperative 36-Item Short Form Health Survey Physical Component Summary (PCS) score as reflected by the number of patients reaching minimal clinically important difference (MCID) and substantial clinical benefit (SCB). Univariate analyses were conducted to identify baseline differences and factors that were significantly related to outcomes at 2 years. Multivariable regression modeling was used as our primary analysis to compare outcomes between groups. The mean age (years) and percent females for the spine, hip, and knee groups were 63.3/58.5, 66.0/46.9, and 65.8/64.3, respectively. All three groups experienced significant improvement of baseline PCS (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.001). Multivariate analyses, adjusting for baseline differences (age, gender, baseline Mental Component Summary score, baseline PCS), demonstrated no significant differences in PCS outcome between spinal surgery and arthroplasty (combined hip and knee cohorts) patients with an odds ratio of 0.80 (95% confidence interval [CI], 0.57-1.11; p=.17) and 0.79 (95% CI, 0.58-1.09; p=.15) for achieving MCID or SCB, respectively. In subgroup analysis, spine and knee outcomes were not significantly different, with hip arthroplasty superior to both (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.0001). Significant improvement in physical HRQoL after surgical treatment of FLSS (including DLS) is consistently achieved nationally. Our overall results demonstrate that a comparable number of patients can expect to achieve MCID and SCB 2 years after surgical intervention for FLSS and total knee arthroplasty.
Nature, 2015
Anxiety-related conditions are among the most difficult neuropsychiatric diseases to treat pharma... more Anxiety-related conditions are among the most difficult neuropsychiatric diseases to treat pharmacologically, but respond to cognitive therapies. There has therefore been interest in identifying relevant top-down pathways from cognitive control regions in medial prefrontal cortex (mPFC). Identification of such pathways could contribute to our understanding of the cognitive regulation of affect, and provide pathways for intervention. Previous studies have suggested that dorsal and ventral mPFC subregions exert opposing effects on fear, as do subregions of other structures. However, precise causal targets for top-down connections among these diverse possibilities have not been established. Here we show that the basomedial amygdala (BMA) represents the major target of ventral mPFC in amygdala in mice. Moreover, BMA neurons differentiate safe and aversive environments, and BMA activation decreases fear-related freezing and high-anxiety states. Lastly, we show that the ventral mPFC-BMA projection implements topdown control of anxiety state and learned freezing, both at baseline and in stress-induced anxiety, defining a broadly relevant new top-down behavioural regulation pathway. Reprints and permissions information is available at www.nature.com/reprints.
Cell, 2014
Social interaction is a complex behavior essential for many species and is impaired in major neur... more Social interaction is a complex behavior essential for many species and is impaired in major neuropsychiatric disorders. Pharmacological studies have implicated certain neurotransmitter systems in social behavior, but circuit-level understanding of endogenous neural activity during social interaction is lacking. We therefore developed and applied a new methodology, termed fiber photometry, to optically record natural neural activity in genetically and connectivity-defined projections to elucidate the realtime role of specified pathways in mammalian behavior. Fiber photometry revealed that activity dynamics of a ventral tegmental area (VTA)-tonucleus accumbens (NAc) projection could encode and predict key features of social, but not novel object, interaction. Consistent with this observation, optogenetic control of cells specifically contributing to this projection was sufficient to modulate social behavior, which was mediated by type 1 dopamine receptor signaling downstream in the NAc. Direct observation of deep projection-specific activity in this way captures a fundamental and previously inaccessible dimension of mammalian circuit dynamics. (A) (Left) Photometry setup. Light path for fluorescence excitation and emission is through a single 400 mm fiber optic implanted in VTA. (Right) Viral targeting of GCaMP5 to VTA-DA neurons.
Objective and Context:Our objective was to examine predictability of reproductive hormone concent... more Objective and Context:Our objective was to examine predictability of reproductive hormone concentrations for bone mineral density (BMD) loss during the menopausal transition. Design: We conducted a longitudinal (five annual examinations), multiple-site (n 5) cohort study, the Study of Women's Health Across the Nation (SWAN). Participants: Participants included, at baseline, 2311 premeno- pausal or early perimenopausal African-American, Caucasian, Chi- nese, and
The Journal of Trauma: Injury, Infection, and Critical Care, 1996
The American journal of clinical nutrition, Jan 8, 2015
Epidemiologic data suggest that low serum 25-hydroxyvitamin D [25(OH)D] increases insulin resista... more Epidemiologic data suggest that low serum 25-hydroxyvitamin D [25(OH)D] increases insulin resistance and the risk of type 2 diabetes. Few interventional trials have assessed the effect of vitamin D on insulin metabolism, and published results are discordant. The goal of this study was to perform a detailed assessment of the effect of ergocalciferol administration on glucose and insulin metabolism in healthy people with low total 25(OH)Dtotal. This was a 12-wk, double-blinded, randomized controlled trial. We enrolled 90 healthy volunteers aged 18-45 y with serum 25(OH)D ≤20 ng/mL (by immunoassay) and administered ergocalciferol 50,000 IU/wk or placebo for 12 wk. Primary endpoints were change in first-phase insulin response and insulin sensitivity as measured by intravenous glucose tolerance test. Secondary endpoints included change in homeostasis model assessment of insulin resistance; fasting glucose, insulin, and lipids; body mass index (BMI); and blood pressure. On-study 25(OH)Dto...
CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne, Jan 6, 2015
Older people are at increased risk of traumatic spinal cord injury from falls. We evaluated the i... more Older people are at increased risk of traumatic spinal cord injury from falls. We evaluated the impact of older age (= 70 yr) on treatment decisions and outcomes. We identified patients with traumatic spinal cord injury for whom consent and detailed data were available from among patients recruited (2004-2013) at any of the 31 acute care and rehabilitation hospitals participating in the Rick Hansen Spinal Cord Injury Registry. Patients were assessed by age group (< 70 v. ≥ 70 yr). The primary outcome was the rate of acute surgical treatment. We used bivariate and multivariate regression models to assess patient and injury-related factors associated with receiving surgical treatment and with the timing of surgery after arrival to a participating centre. Of the 1440 patients included in our study cohort, 167 (11.6%) were 70 years or older at the time of injury. Older patients were more likely than younger patients to be injured by falling (83.1% v. 37.4%; p < 0.001), to have a c...
NMR in Biomedicine, 2015
Quantitative T2 (qT2), diffusion tensor imaging (DTI), and histology were used to investigate a c... more Quantitative T2 (qT2), diffusion tensor imaging (DTI), and histology were used to investigate a cervical model of spinal cord injury (SCI) in the rat. While quantitative MRI can significantly increase the specificity in the presence of pathology, it must be validated for each type of injury or disease. In the case of traumatic SCI most models are difficult to image, either due to the location of the injury, or as a result of damage to surrounding tissues resulting from invasive surgical procedures. In this study a non-surgical cervical model of SCI, produced using a combination of focused ultrasound and microbubbles, was used to produce pathology similar to that seen in models of contusive and compressive injuries. qT2 and DTI were performed at 24 h and 1 and 2 weeks following injury, and compared with H&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;E and luxol fast blue histology. In the injured spinal cord, in addition to intra/extracellular (I/E) water and myelin water in white matter, qT2 revealed a large component with very short T2 of about 3 ms, which was highly correlated with the presence of hemorrhage in both gray and white matter at 24 h, and with the presence of hemosiderin in gray matter at 2 weeks following injury. The T2 of the I/E water peak was also elevated at 24 h in both gray and white matter, which was correlated with the presence of vacuolation/edema on histology. Cystic cavities were only seen at the 1 or 2 week timepoints, and were correlated with the presence of a water peak with T2 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 250 ms. No significant changes in diffusivity parameters were observed. Pathologies were often co-occurring, with opposite effects on the average T2 in a given voxel, reducing the visibility of injured tissue on standard T2 -weighted MR images. Copyright © 2015 John Wiley &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp; Sons, Ltd.
Current Orthopaedic Practice, 2011
ABSTRACT Background: The goal of this study was to evaluate a new second generation of computer-a... more ABSTRACT Background: The goal of this study was to evaluate a new second generation of computer-assisted fluoroscopic navigation software for fracture reduction (SGFR) of long-bone fractures. The new software allows simultaneous tracking of two moving bone fragments. Methods: Between 2005–2007, patients with isolated, extra-articular long-bone fracture of either the femur or tibia were considered for computer-assisted fluoroscopic fracture reduction surgery. The operative tasks were: (1) fracture reduction; (2) determination of the entry point, and; (3) Poller screw insertion, when needed. Fracture reduction was achieved by one of two methods: (1) fracture edges or (2) medullary canal recognition. Fracture reduction was considered successful if the guide wire was introduced through the fracture without further radiation. Results: We treated 38 patients (27 men and 11 women); with 15 femoral and 23 tibial fractures, with intramedullary nail fixation. In all patients, the point of entry was navigated successfully. In four patients, the insertion of the blocking screw was planned and executed without further radiation. All fractures were successfully reduced using the SGFR system. In nine patients, we used method 1, in 22 patients method 2, and in six a combination of both. The number of fluoroscopic images was dramatically reduced to four to six images. Conclusions: Fracture reduction was reliably achievable in all patients using the SGFR. A key conclusion is that only a small number of fluoroscopic images are required. Although timing was not an objective of this study, we believe that there was a noticeable reduction of intraoperative time.
Cell, 2014
Social interaction is a complex behavior essential for many species and is impaired in major neur... more Social interaction is a complex behavior essential for many species and is impaired in major neuropsychiatric disorders. Pharmacological studies have implicated certain neurotransmitter systems in social behavior, but circuit-level understanding of endogenous neural activity during social interaction is lacking. We therefore developed and applied a new methodology, termed fiber photometry, to optically record natural neural activity in genetically and connectivity-defined projections to elucidate the real-time role of specified pathways in mammalian behavior. Fiber photometry revealed that activity dynamics of a ventral tegmental area (VTA)-to-nucleus accumbens (NAc) projection could encode and predict key features of social, but not novel object, interaction. Consistent with this observation, optogenetic control of cells specifically contributing to this projection was sufficient to modulate social behavior, which was mediated by type 1 dopamine receptor signaling downstream in the NAc. Direct observation of deep projection-specific activity in this way captures a fundamental and previously inaccessible dimension of mammalian circuit dynamics.
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, Jan 16, 2015
Improvements in clinical care have led to increased life expectancy in patients with cystic fibro... more Improvements in clinical care have led to increased life expectancy in patients with cystic fibrosis (CF) over the past several decades. Whether these improvements have had significant effects on bone health in patients with CF is unclear. This is a cross-sectional study comparing clinical characteristics and bone mineral density (BMD) measured by dual energy X-ray absorptiometry (DXA) in adults with CF evaluated in 1995-1999 to age-, race-, and gender-matched patients with CF evaluated in 2011-2013 at the same center on calibrated DXA machines. The cohorts were similar in terms of age, BMI, pancreatic insufficiency, presence of F508del mutation, and reproductive history. In the most recent cohort, pulmonary function was superior, and fewer patients had vitamin D deficiency or secondary hyperparathyroidism. Areal BMD measures of the PA spine, lateral spine, and distal radius were similarly low in the two cohorts. Although pulmonary function and vitamin D status were better in patien...
Journal of Spinal Disorders, 1999
A prospective cohort study of consecutive patients with thoracolumbar fractures from two centers ... more A prospective cohort study of consecutive patients with thoracolumbar fractures from two centers was conducted to evaluate the use of cortical allograft for anterior spine reconstruction. The purpose was to determine whether allograft bone had deleterious effects on fusion rates and maintenance of correction. Thirty-six patients were followed for a minimum of 2 years. A radiologic fusion rate of 81% was found, and there was a loss of postoperative correction in eight patients. The addition of posterior instrumentation was not significantly different from anterior surgery alone with respect to union rates but did provide a more reliable maintenance of correction of deformity. There were no cases of disease transmission. The authors conclude that cortical allograft for anterior spine reconstruction in trauma is safe and despite having a fusion rate lower than autogenous iliac crest, little clinical significance is attributable to the radiologic appearance of nonunion at the host-allograft junctions.
Long-term compliance with pharmacologic treatments for many asymptomatic conditions may be subopt... more Long-term compliance with pharmacologic treatments for many asymptomatic conditions may be suboptimal, but little is known about compliance with medications used for osteoporosis. This study was undertaken to assess the level and determinants of compliance with drugs prescribed for osteoporosis. This retrospective cohort study used pharmacy claims data from US Medicare and filled prescriptions from a state pharmaceutical benefits program. We included persons 65 years or older who initiated use of a medication for osteoporosis (alendronate sodium, calcitonin, hormone therapy, raloxifene hydrochloride, or risedronate) from January 1, 1996, through December 31, 2002. The outcome of interest was suboptimal medication compliance, defined as equal to or less than 66% of days with medication during a 60-day period. One year after initiating treatment for osteoporosis, 45.2% of the 40,002 patients were not continuing to fill prescriptions. Five years after initiation, 52.1% of patients were not continuing to fill prescriptions for an osteoporosis medication. Several characteristics independently predicted compliance: female sex, younger age, fewer comorbid conditions, using fewer nonosteoporosis medications, bone mineral density testing before and after initiating a medication, a fracture before and after initiating a medication, and nursing home residence during the 12 months before initiating a medication. However, models adjusted for the significant patient variables explained only 6% of the variation in compliance. Most patients who initiate a medication for osteoporosis do not continue to take it as prescribed. Although several patient characteristics significantly correlated with compliance, adjusted models explained little of the variation.
Cancer Metastasis – Biology and Treatment, 2009
Orthopaedic and spinal surgery can provide significant palliation to patients with symptoms arisi... more Orthopaedic and spinal surgery can provide significant palliation to patients with symptoms arising for bony metastatic involvement in addition to patients that are at risk for skeletally related events (SREs). This chapter will review the role of surgery in the management of bone metastases and discuss factors that need to be considered prior to surgery. The treatment of pathologic fractures
Annals of Vascular Surgery, 1993
This case presentation reports the second case of axillary artery thrombosis secondary to pectora... more This case presentation reports the second case of axillary artery thrombosis secondary to pectoralis minor compression. Evidence to explain this etiology is presented from arteriographic and intraoperative clinical findings. Management includes division of the pectoralis minor muscle and local arterial repair if the vessel is severely damaged. (Ann Vasc Surg 1993;7:287-290.) In the spectrum of thoracic outlet syndrome, arterial compression occurs in less than 5 % of all patients. ~ Compression of the subclavian artery is primarily in the costoscalene passage where bony abnormalities, including cervical ribs and fibrous bands, have been recognized. 2 Less frequently, compression may occur at the costoclavicular space. ~ The importance of the .hyperabduction syndrome and the pectoralis minor tendon as a cause of axillary artery compression has also been well described. 4-6 However, to our knowledge, only one case of axillary artery thrombosis secondary to pectoralis minor compression has been reported. ~ We report a case of axillary artery thrombosis secondary to compression by the pectoralis minor with thromboembolism occluding the radial and ulnar arteries.
International Quarterly of Community Health Education, 2008
Objective-To better understand high-risk patients' readiness to engage in bone mineral density (B... more Objective-To better understand high-risk patients' readiness to engage in bone mineral density (BMD) testing to diagnose osteoporosis.
Mayo Clinic Proceedings, 2005
To assess current osteoporosis treatment guidelines, studies of osteoporosis treatment, and inter... more To assess current osteoporosis treatment guidelines, studies of osteoporosis treatment, and interventions to improve osteoporosis treatment. We searched the medical literature for articles published between January 1, 1992, and December 31, 2003, and assessed all relevant articles using a structured data abstraction process. Because of substantial heterogeneity in study design, no attempt was made to summarize the data using meta-analytic techniques. Seventy-six articles met criteria for inclusion. Eighteen practice guidelines were studied. Most guidelines were consistent in key treatment recommendations. Among 18 studies of treatment rates in patients who had fractures, the weighted average varied from 22% for nonhormonal treatment to 19% for calcium. We found slightly higher treatment rates for patients taking oral glucocorticoids or for those older than 65 years. There were no consistent correlates of which patients received treatment. Six studies that examined treatment frequencies after bone densitometry all found that patients with lower bone mineral density were more likely to receive treatment. Most of the 8 interventions designed to improve osteoporosis treatment showed improvement in treatment rates; however, only 3 were randomized, and these showed the smallest effects. Frequency of treatment of osteoporosis in at-risk populations is low. However, our assessment of the literature revealed no clear and consistent predictors of undertreatment. Few carefully controlled interventions have been reported.
The Spine Journal, 2010
ABSTRACT Decompression alone (D) is a well-accepted treatment for patients with lumbar spinal ste... more ABSTRACT Decompression alone (D) is a well-accepted treatment for patients with lumbar spinal stenosis (LSS) causing neurogenic claudication; however, D is controversial in patients with LSS who have degenerative spondylolisthesis (DLS). Our goal was to compare the outcome of anatomy-preserving D with decompression and fusion (DF) for patients with grade I DLS. We compared patients with DLS who had elective primary 1-2 level spinal D at 1 centre with a cohort who had 1-2 level spinal DF at 5 other centres.
The Spine Journal, 2011
The results of single-center studies have shown that surgical intervention for lumbar spinal sten... more The results of single-center studies have shown that surgical intervention for lumbar spinal stenosis yielded comparable health-related quality of life (HRQoL) improvement to total joint arthroplasty (TJA). Whether these results are generalizable to routine clinical practice in Canada is unknown. The primary purpose of this equivalence study was to compare the relative improvement in physical HRQoL after surgery for focal lumbar spinal stenosis (FLSS) compared with TJA for hip and knee osteoarthritis (OA) across six Canadian centers. A Canadian multicenter ambispective cohort study. A cohort of 371 primary one- to two-level spinal decompression (n=214 with instrumented fusion) for FLSS (n=179 with degenerative lumbar spondylolisthesis [DLS]) was compared with a cohort of primary total hip (n=156) and knee (n=208) arthroplasty for OA. The primary outcome was the change in preoperative to 2-year postoperative 36-Item Short Form Health Survey Physical Component Summary (PCS) score as reflected by the number of patients reaching minimal clinically important difference (MCID) and substantial clinical benefit (SCB). Univariate analyses were conducted to identify baseline differences and factors that were significantly related to outcomes at 2 years. Multivariable regression modeling was used as our primary analysis to compare outcomes between groups. The mean age (years) and percent females for the spine, hip, and knee groups were 63.3/58.5, 66.0/46.9, and 65.8/64.3, respectively. All three groups experienced significant improvement of baseline PCS (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.001). Multivariate analyses, adjusting for baseline differences (age, gender, baseline Mental Component Summary score, baseline PCS), demonstrated no significant differences in PCS outcome between spinal surgery and arthroplasty (combined hip and knee cohorts) patients with an odds ratio of 0.80 (95% confidence interval [CI], 0.57-1.11; p=.17) and 0.79 (95% CI, 0.58-1.09; p=.15) for achieving MCID or SCB, respectively. In subgroup analysis, spine and knee outcomes were not significantly different, with hip arthroplasty superior to both (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.0001). Significant improvement in physical HRQoL after surgical treatment of FLSS (including DLS) is consistently achieved nationally. Our overall results demonstrate that a comparable number of patients can expect to achieve MCID and SCB 2 years after surgical intervention for FLSS and total knee arthroplasty.