Steward St Elizabeths Medical Center

Cambridge, MA, United States

Steward St Elizabeths Medical Center

Cambridge, MA, United States
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Defelipe J.,Technical University of Madrid | Defelipe J.,Instituto Cajal CSIC | Lopez-Cruz P.L.,Technical University of Madrid | Benavides-Piccione R.,Technical University of Madrid | And 42 more authors.
Nature Reviews Neuroscience | Year: 2013

A systematic classification and accepted nomenclature of neuron types is much needed but is currently lacking. This article describes a possible taxonomical solution for classifying GABAergic interneurons of the cerebral cortex based on a novel, web-based interactive system that allows experts to classify neurons with pre-determined criteria. Using Bayesian analysis and clustering algorithms on the resulting data, we investigated the suitability of several anatomical terms and neuron names for cortical GABAergic interneurons. Moreover, we show that supervised classification models could automatically categorize interneurons in agreement with experts' assignments. These results demonstrate a practical and objective approach to the naming, characterization and classification of neurons based on community consensus. © 2013 Macmillan Publishers Limited. All rights reserved.

Saviet B.M.,Steward St Elizabeths Medical Center | Marcoux J.T.,Steward St Elizabeths Medical Center | Narayanasami U.,Tufts University
Journal of Foot and Ankle Surgery | Year: 2017

Multiple myeloma is a malignancy of plasma cell proliferation leading to production of monoclonal immunoglobins. Among the classic features of multiple myeloma are bone lesions, which typically manifest in the axial skeleton, vertebrae, pelvis, skull, ribs, and proximal extremities. The several types of multiple myeloma include symptomatic multiple myeloma, monoclonal gammopathy of undetermined significance, smoldering/indolent myeloma, and solitary plasmacytoma of bone. Although rare, plasmacytomas of the foot and ankle have been described in published studies. We present, to the best of our knowledge, the first description of classic diffuse myelomatosis lesions associated with symptomatic myeloma in the foot of a patient with advanced disease who was treated in the podiatric surgery clinic for pathologic fracture. © 2016 American College of Foot and Ankle Surgeons

Hoben R.,Steward St Elizabeths Medical Center | Easow G.,Steward St Elizabeths Medical Center | Pevzner S.,Steward St Elizabeths Medical Center | Parker M.A.,Steward St Elizabeths Medical Center | Parker M.A.,Tufts University
Frontiers in Neuroscience | Year: 2017

The goal of this study was to describe the contribution of outer hair cells (OHCs) and the auditory nerve (AN) to speech understanding in quiet and in the presence of background noise. Fifty-three human subjects with hearing ranging from normal to moderate sensorineural hearing loss were assayed for both speech in quiet (Word Recognition) and speech in noise (QuickSIN test) performance. Their scores were correlated with OHC function as assessed via distortion product otoacoustic emissions, and AN function as measured by amplitude, latency, and threshold of the VIIIth cranial nerve Compound Action Potential (CAP) recorded during electrocochleography (ECochG). Speech and ECochG stimuli were presented at equivalent sensation levels in order to control for the degree of hearing sensitivity across patients. The results indicated that (1) OHC dysfunction was evident in the lower range of normal audiometric thresholds, which demonstrates that OHC damage can produce "Hidden Hearing Loss," (2) AN dysfunction was evident beginning at mild levels of hearing loss, (3) when controlled for normal OHC function, persons exhibiting either high or low ECochG amplitudes exhibited no statistically significant differences in neither speech in quiet nor speech in noise performance, (4) speech in noise performance was correlated with OHC function, (5) hearing impaired subjects with OHC dysfunction exhibited better speech in quiet performance at or near threshold when stimuli were presented at equivalent sensation levels. These results show that OHC dysfunction contributes to hidden hearing loss, OHC function is required for optimum speech in noise performance, and those persons with sensorineural hearing loss exhibit better word discrimination in quiet at or near their audiometric thresholds than normal listeners. © 2017 Hoben, Easow, Pevzner and Parker.

Wamelink K.E.,Steward St Elizabeths Medical Center | Marcoux J.T.,Steward St Elizabeth Medical Center | Walrath S.M.,Saint Vincent Hospital
Journal of Foot and Ankle Surgery | Year: 2016

Before the report of English surgeon Robert Jones, who sustained a fracture to his fifth metatarsal while dancing around a tent pole, metatarsal fractures were thought to be the result of direct trauma to the foot. The mechanism of metatarsal fractures, in particular, those involving the fifth metatarsal, is now well understood. Patients with an adducted alignment of their forefoot can overload the fifth metatarsal base, putting them at an increased risk of fractures of this bone. Studies have reported that 2 distinct types of proximal diaphyseal or junctional fractures of the fifth metatarsal occur: the acute proximal diaphyseal or transverse proximal diaphyseal fracture and the proximal diaphyseal stress fracture. The radiographic characteristics associated with proximal diaphyseal stress fractures of the fifth metatarsal can vary by the chronicity; however, the findings typically entail a radiolucent fracture line with surrounding reactive sclerosis. In addition, a reduced medullary canal width can be appreciated. In the present retrospective analysis of patients with stress-related trauma to the fifth metatarsal base with an adducted forefoot, 2012 foot trauma cases were reviewed at 3 separate institutions. Of the 2012 cases, 22 (1.11%) met the outlined criteria of stress fractures of the fifth metatarsal base and underlying metatarsus adductus. © 2016 American College of Foot and Ankle Surgeons.

Mijailovich S.M.,Harvard University | Mijailovich S.M.,Tufts University | Mijailovich S.M.,Steward St Elizabeths Medical Center | Kayser-Herold O.,Harvard University | And 3 more authors.
European Biophysics Journal | Year: 2012

The regulation of striated muscle contraction involves cooperative interactions between actin filaments, myosin-S1 (S1), tropomyosin (Tm), troponin (Tn), and calcium. These interactions are modeled by treating overlapping tropomyosins as a continuous flexible chain (CFC), weakly confined by electrostatic interactions with actin. The CFC is displaced locally in opposite directions on the actin surface by the binding of either S1 or Troponin I (TnI) to actin. The apparent rate constants for myosin and TnI binding to and detachment from actin are then intrinsically coupled via the CFC model to the presence of neighboring bound S1s and TnIs. Monte Carlo simulations at prescribed values of the CFC stiffness, the CFC's degree of azimuthal confinement, and the angular displacements caused by the bound proteins were able to predict the stopped-flow transients of S1 binding to regulated F-actin. The transients collected over a large range of calcium concentrations could be well described by adjusting a single calcium-dependent parameter, the rate constant of TnI detachment from actin, k -I. The resulting equilibrium constant KB ≡ 1/KI varied sigmoidally with the free calcium, increasing from 0.12 at low calcium (pCa >7) to 12 at high calcium (pCa <5.5) with a Hill coefficient of ~2.15. The similarity of the curves for excess-actin and excess-myosin data confirms their allosteric relationship. The spatially explicit calculations confirmed variable sizes for the cooperative units and clustering of bound myosins at low calcium concentrations. Moreover, inclusion of negative cooperativity between myosin units predicted the observed slowing of myosin binding at excess-myosin concentrations. © 2012 The Author(s).

Silvestri G.A.,Medical University of South Carolina | Feller-Kopman D.,Johns Hopkins University | Chen A.,University of Washington | Wahidi M.,Duke University | And 2 more authors.
Chest | Year: 2012

Over the past 15 years, patients with a myriad of pulmonary conditions have been diagnosed and treated with new technologies developed for the pulmonary community. Advanced diagnostic and therapeutic procedures once performed in an operating theater under general anesthesia are now routinely performed in a bronchoscopy suite under moderate sedation with clinically meaningful improvements in outcome. With the miniaturization of scopes and instruments, improvements in optics, and creative engineers, a host of new devices has become available for clinical testing and use. A growing community of pulmonologists is doing comparative effectiveness trials that test new technologies against the current standard of care. While more research is needed, it seems reasonable to provide an overview of pulmonary procedures that are in various stages of development, testing, and practice at this time. Five areas are covered: navigational bronchoscopy, endobronchial ultrasound, endoscopic lung volume reduction, bronchial thermoplasty, and pleural procedure. Appropriate training for clinicians who wish to provide these services will become an area of intense scrutiny as new skills will need to be acquired to ensure patient safety and a good clinical result. © 2012 American College of Chest Physicians.

Lovich M.A.,Steward St Elizabeths Medical Center | Wakim M.G.,Steward St Elizabeths Medical Center | Wei A.,Steward St Elizabeths Medical Center | Parker M.J.,Beth Israel Deaconess Medical Center | And 4 more authors.
Anesthesia and Analgesia | Year: 2013

BACKGROUND:: IV infusion systems can be configured with manifolds connecting multiple drug infusion lines to transcutaneous catheters. Prior in vitro studies suggest that there may be significant lag times for drug delivery to reflect changes in infusion rates set at the pump, especially with low drug and carrier flows and larger infusion system dead-volumes. Drug manifolds allow multiple infusions to connect to a single catheter port but add dead-volume. We hypothesized that the time course of physiological responses to drug infusion in vivo reflects the impact of dead-volume on drug delivery. METHODS:: The kinetic response to starting and stopping epinephrine infusion ([3 mL/h] with constant carrier flow [10 mL/h]) was compared for high- and low-dead-volume manifolds in vitro and in vivo. A manifold consisting of 4 sequential stopcocks with drug entering at the most upstream port was contrasted with a novel design comprising a tube with separate coaxial channels meeting at the downstream connector to the catheter, which virtually eliminates the manifold contribution to the dead-volume. The time to 50% (T50) and 90% (T90) increase or decrease in drug delivery in vitro or contractile response in a swine model in vivo were calculated for initiation and cessation of drug infusion. RESULTS:: The time to steady state after initiation and cessation of drug infusion both in vitro and in vivo was much less with the coaxial low-dead-volume manifold than with the high-volume design. Drug delivery after initiation in vitro reached 50% and 90% of steady state in 1.4 ± 0.12 and 2.2 ± 0.42 minutes with the low-dead-volume manifold and in 7.1 ± 0.58 and 9.8 ± 1.6 minutes with the high-dead-volume manifold, respectively. The contractility in vivo reached 50% and 90% of the full response after drug initiation in 4.3 ± 1.3 and 9.9 ± 3.9 minutes with the low-dead-volume manifold and 11 ± 1.2 and 17 ± 2.6 minutes with the high-dead-volume manifold, respectively. Drug delivery in vitro decreased by 50% and 90% after drug cessation in 1.9 ± 0.17 and 3.5 ± 0.61 minutes with the low-dead-volume manifold and 10.0 ± 1.0 and 17.0 ± 2.8 minutes with the high-dead-volume manifold, respectively. The contractility in vivo decreased by 50% and 90% with drug cessation in 4.1 ± 1.1 and 14 ± 5.2 with the low-dead-volume manifold and 12 ± 2.7 and 23 ± 5.6 minutes with the high-dead-volume manifold, respectively. CONCLUSIONS:: The architecture of the manifold impacts the in vivo biologic response, and the drug delivery rate, to changes in drug infusion rate set at the pump. Copyright © 2013 International Anesthesia Research Society.

Lovich M.A.,Steward St Elizabeths Medical Center | Pezone M.J.,Steward St Elizabeths Medical Center | Maslov M.Y.,Steward St Elizabeths Medical Center | Murray M.R.,Steward St Elizabeths Medical Center | And 2 more authors.
Anesthesia and Analgesia | Year: 2015

BACKGROUND: We have previously shown that, at constant carrier flow, drug infusion systems with large dead-volumes (V) slow the time to steady-state drug delivery in vitro and pharmacodynamic effect in vivo compared to those with smaller V. In this study, we tested whether clinically relevant alterations in carrier flow generate perturbations in drug delivery and pharmacodynamic effect, and how these might be magnified when V is large. METHODS: Drug delivery in vitro or mean arterial blood pressure (MAP) and ventricular contractility (max dP/dt) in a swine model were quantified during an infusion of norepinephrine (fixed rate 3 mL/h) with a crystalloid carrier (10 mL/h). The carrier flow was transiently halted for either 10 minutes or 20 minutes and then restarted. In separate experiments, a second drug infusion (50 mL over 10 minutes) was introduced into the same catheter lumen used by a steady-state norepinephrine infusion. The resulting perturbations in drug delivery and biologic effect were compared between drug infusion systems with large and small V. RESULTS: Halting carrier flow immediately decreased drug delivery in vitro, and MAP and max dP/dt. These returned to steady state before restarting carrier flow with the small, but not the large, V. Resuming carrier flow after 10 minutes resulted in a transient increase in drug delivery in vitro and max dP/dt in vivo, which were of longer duration and greater area under the curve (AUC) for larger V. MAP also increased for longer duration for larger V. Resuming the carrier flow after 20 minutes resulted in greater AUCs for drug delivery, MAP, and max dP/dt for the larger V. Adding a second infusion to a steady-state norepinephrine plus carrier flow initially resulted in a drug bolus in vitro and augmented contractility response in vivo, both greater with a larger V. Steady-state drug delivery resumed before the secondary infusion finished. After the end of the secondary infusion drug delivery, MAP and max dP/dt decreased over minutes. Drug delivery and max dP/dt returned to steady state more quickly with the small V. CONCLUSIONS: Stopping and resuming a carrier flow, or introducing a second medication infusion, impacts drug delivery in vitro and biologic response in vivo. Infusion systems with small dead-volumes minimize these perturbations and dampen the resulting hemodynamic instability. Alterations in carrier flow impact drug delivery, resulting in substantial effects on physiologic responses. Therefore, infusion systems for vasoactive drugs should be configured with small V when possible. © 2015 International Anesthesia Research Society.

Grant P.A.,Slippery Rock University | Grant N.A.,Steward St Elizabeths Medical Center
Advances in Special Education | Year: 2015

The treatment and care of persons with a disability should and must be all encompassing. With the expansion of the knowledge that proper dieting can make a difference in the individual's development and quality of life, attention must be focused on using proper food intake to remediate the negative impact of a disability. Food is related to proper healthcare; therefore, we must include proper nutrition in working with learners with exceptionalities. We must add to the list of treatments not only educational intervention, social interaction, and independent living, but also food intake. This chapter looks at the dietary needs of several disabling conditions, and addresses how particular dietary food selections help in their development and their ability to learn integration, playing skills with others, and working independently when called on to do so. Therefore, for the purposes of this chapter, we focus on exceptionalities such as cognitive disability, autism spectrum disorder (ASD), Down syndrome, attention deficit hyperactivity disorder (ADHD), muscular dystrophy, and cystic fibrosis. © 2015 by Emerald Group Publishing Limited.

PubMed | Steward St Elizabeths Medical Center and Tufts University
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2017

87 Background: The overall incidence of SLN metastases in pure DCIS is < 1% and the results of SLNB do not usually impact treatment or survival but adds significant surgical morbidity. In addition, there is no evidence regarding the role of preoperative MRI in the management of DCIS. The purpose of our study was to identify the efficacy of SLNB and the benefit of preoperative MRI in high-grade DCIS.We performed retrospective review of 364 patients with DCIS, identified through our cancer registry database, that were seen from 2003 to 2012 at our institution. Of these, 62 patients were diagnosed with high-grade DCIS (Grade 3 or 2 with comedonecrosis) by core needle biopsy, and underwent SLNB. The remaining 302 patients had either low-grade DCIS or did not have a SLNB.Median age was 56 years (range 33-80). Sixty two patients had high-grade DCIS on definitive excision and 2/62 patients were noted to have small invasive focus of disease. 15/62 (24.19%) patients underwent mastectomy and 47/62(78.1%) underwent lumpectomy. No patient had a positive SLN (0/62). 15/62 (24.2%) patients had breast MRI preoperatively and among them, in 5 (33.3%) patients, MRI findings changed the surgical decision to mastectomy. Among these 5 mastectomy patients, four of them (80%) had pathologically confirmed findings consistent with preoperative MRI suspicions. In lumpectomy patients, close margin of less than 1mm was seen in 4/9 (44.4%) patients with staging MRI and in 24/38 (63.15%) patients without MRI (p = 0.45. Fishers exact test). However the positive margin leading to re-excision was seen in 2/9 (22.2%) patients who underwent lumpectomy with staging MRI, and 9/38 (23.6%) patients who underwent lumpectomy without staging MRI.In our study, no patient with high grade DCIS had a positive sentinel node suggesting that routine sentinel node biopsy is not necessary in DCIS patients. The use of MRI changed the surgical planning in 33.3% of patients, but did not improve the surgeons ability to achieve clear margins.

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