Mostrando recursos 1 - 20 de 10.646

  1. Widespread effects of clinically unilateral focal nerve injuries

    Hamrah, Pedram; Sahin, Afsun; Oaklander, Anne Louise

  2. Evidence of small-fiber neuropathy (SFN) in two patients with unexplained genital sensory loss and sensory urinary cystopathy

    AbdelRazek, Mahmoud A.; Chwalisz, Bart K; Oaklander, Anne Louise; Venna, Nagagopal
    The term small-fiber neuropathy (SFN) refers to the type of polyneuropathies that preferentially damage the small unmyelinated and thinly myelinated sensory or autonomic neurons [1]. Skin biopsy to determine the epidermal nerve-fiber density (ENFD) is the most de- finitive method in the diagnosis of SFN, but autonomic function testing can also be useful [2]. Importantly, electromyography and surface nerve-conduction studies (EMG/NCS) do not capture the small scattered action potentials of small fibers, and thus are insensitive to small-fiber restricted neuropathies. Quantitative sensory testing is a subjective test that depends on patient volition, so it is not recommend- ed or reimbursed...

  3. Initial Development and Validation of a Patient-Reported Symptom Survey for Small-Fiber Polyneuropathy

    Treister, Roi; Lodahl, Mette; Lang, Magdalena; Tworoger, Shelley Slate; Sawilowsky, Shlomo; Oaklander, Anne Louise
    Small-fiber polyneuropathy (SFPN) affects unmyelinated and thinly myelinated peripheral axons. Several questionnaires have been developed to assess polyneuropathy from diabetes or chemotherapy, but none for SFPN from other or unknown causes. A comprehensive survey could help clinicians diagnose and assess treatment responses, define prevalence natural history and cures, and identify research subjects. Thus, we developed the 1-page Small-Fiber Symptom Survey, using input from patients and 21 medical/scientific experts. Participants comprised consenting consecutive patients evaluated for SFPN at the Massachusetts General Hospital plus normal control subjects. Par- ticipants SFPN status was stratified on the basis of the results of their objective...

  4. Time-variant fMRI activity in the brainstem and higher structures in response to acupuncture

    Napadow, Vitaly J.; Dhond, Rupali; Park, Kyungmo; Kim, Jieun; Makris, Nikos; Kwong, Kenneth Kin Man; Harris, Richard E.; Purdon, Patrick Lee; Kettner, Norman; Hui, Kathleen K.S.
    Acupuncture modulation of activity in the human brainstem is not well known. This structure is plagued by physiological artifact in neuroimaging experiments. In addition, most studies have used short (<15min) block designs, which miss delayed responses following longer duration stimulation. We used brainstem-focused cardiac-gated fMRI and evaluated time-variant brain response to longer duration (>30min) stimulation with verum (VA, electrostimulation at acupoint ST-36) or sham point (SPA, non-acupoint electrostimulation) acupuncture. Our results provide evidence that acupuncture modulates brainstem nuclei important to endogenous monoaminergic and opioidergic systems. Specifically, VA modulated activity in the substantia nigra (SN), nucleus raphe magnus, locus ceruleus, nucleus...

  5. Frontolimbic neural circuit changes in emotional processing and inhibitory control associated with clinical improvement following transference-focused psychotherapy in borderline personality disorder

    Perez, David L.; Vago, David R.; Pan, Hong; Root, James; Tuescher, Oliver; Fuchs, Benjamin H.; Leung, Lorene; Epstein, Jane Ingrid; Cain, Nicole M.; Clarkin, John F.; Lenzenweger, Mark F.; Kernberg, Otto F.; Levy, Kenneth N.; Silbersweig, David A; Stern, Emily
    Aim Borderline personality disorder (BPD) is characterized by self-regulation deficits, including impulsivity and affective lability. Transference-Focused Psychotherapy (TFP) is an evidence-based treatment proven to reduce symptoms across multiple cognitive-emotional domains in BPD. This pilot study aims to investigate neural activation associated with, and predictive of, clinical improvement in emotional and behavioral regulation in BPD following TFP. Methods BPD subjects (N=10) were scanned pre- and post-TFP treatment using a within-subjects design. A disorder-specific emotional-linguistic go/no-go fMRI paradigm was used to probe the interaction between negative emotional processing and inhibitory control. Results Analyses demonstrated significant treatment-related effects with relative increased dorsal prefrontal (dorsal anterior cingulate, dorsolateral prefrontal,...

  6. Beyond the amygdala: Linguistic threat modulates peri-sylvian semantic access cortices

    Weisholtz, Daniel; Root, James C.; Butler, Tracy; Tüscher, Oliver; Epstein, Jane Ingrid; Pan, Hong; Protopopescu, Xenia; Goldstein, Martin; Isenberg, Nancy; Brendel, Gary; LeDoux, Joseph; Silbersweig, David A; Stern, Emily
    In this study, healthy volunteers were scanned using functional magnetic resonance imaging (fMRI) to investigate the neural systems involved in processing the threatening content conveyed via visually presented “threat words.” The neural responses elicited by these words were compared to those elicited by matched neutral control words. The results demonstrate that linguistic threat, when presented in written form, can selectively engage areas of lateral temporal and inferior frontal cortex, distinct from the core language areas implicated in aphasia. Additionally, linguistic threat modulates neural activity in visceral/emotional systems (amygdala, parahippocampal gyrus and periaqueductal gray), and at earlier stages of the visual-linguistic...

  7. Rapidly fatal advanced EGFR -mutated lung cancers and the need for rapid tumor genotyping in clinical practice

    Rangachari, Deepa; Drake, Lauren; Huberman, Mark S.; McDonald, Danielle C.; Vanderlaan, Paul A; Folch, Erik E; Costa, Daniel Botelho
    Use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is associated with dramatic, durable, and tolerable responses and side effect profiles, respectively, when applied for palliation of advanced EGFR-mutated non-small-cell lung cancers (NSCLCs). Expert guidelines recommend that EGFR mutation testing results should be available within 10 working days of receipt of tumor specimen by the testing laboratory; in circumstances where the tumor specimen needs to be sent to an external laboratory for testing, the sample should be sent within 3 working days of receiving the request for testing. We report here 2 cases, out of 109 EGFR-mutated (exon...

  8. Experience with targeted next generation sequencing for the care of lung cancer: Insights into promises and limitations of genomic oncology in day-to-day practice

    Rangachari, Deepa; Vanderlaan, Paul A; Le, Xiuning; Folch, Erik E; Kent, Michael; Gangadharan, Sidhu; Majid, Adnan; Haspel, Richard Lawrence; Joseph, Loren Jay; Huberman, Mark S.; Costa, Daniel Botelho
    Introduction Tumor genotyping using single gene assays (SGAs) is standard practice in advanced non-small-cell lung cancer (NSCLC). We evaluated how the introduction of next generation sequencing (NGS) into day-to-day clinical practice altered therapeutic decision-making. Methods Clinicopathologic data, tumor genotype, and clinical decisions were retrospectively compiled over 6 months following introduction of NGS assay use at our institution in 82 patient-tumor samples (7 by primary NGS, 22 by sequential SGAs followed by NGS, and 53 by SGAs). Results SGAs identified abnormalities in 34 samples, and all patients with advanced EGFR-mutated or ALK-rearranged tumors received approved tyrosine kinase inhibitors (TKIs) or were consented for clinical trials. NGS...

  9. Characterizing Acupuncture Stimuli Using Brain Imaging with fMRI - A Systematic Review and Meta-Analysis of the Literature

    Huang, Wenjing; Pach, Daniel; Napadow, Vitaly J.; Park, Kyungmo; Long, Xiangyu; Neumann, Jane; Maeda, Yumi; Nierhaus, Till; Liang, Fanrong; Witt, Claudia M.
    Background The mechanisms of action underlying acupuncture, including acupuncture point specificity, are not well understood. In the previous decade, an increasing number of studies have applied fMRI to investigate brain response to acupuncture stimulation. Our aim was to provide a systematic overview of acupuncture fMRI research considering the following aspects: 1) differences between verum and sham acupuncture, 2) differences due to various methods of acupuncture manipulation, 3) differences between patients and healthy volunteers, 4) differences between different acupuncture points. Methodology/Principal Findings We systematically searched English, Chinese, Korean and Japanese databases for literature published from the earliest available up until September 2009, without any...

  10. Tunneled Pleural Catheter Placement with and without Talc Poudrage for Treatment of Pleural Effusions Due to Congestive Heart Failure

    Majid, Adnan; Kheir, Fayez; Fashjian, Meghan; Chatterji, Sumit; Fernandez-Bussy, Sebastian; Ochoa, Sebastian; Cheng, George; Folch, Erik E
    RATIONALE There is a paucity of evidence regarding the role of tunneled pleural catheters in pleural effusions caused by congestive heart failure that is refractory to medical management. OBJECTIVES: The aim of this study was to assess the feasibility of tunneled pleural catheter drainage for treatment of refractory pleural effusions associated with congestive heart failure, either when used alone or with concomitant talc pleurodesis performed during thoracoscopy. METHODS: This was a retrospective cohort study. We identified patients with congestive heart failure and recurrent symptomatic pleural effusions who were treated between 2005 and 2015 by placement of a tunneled pleural catheter. Patients underwent either thoracoscopy followed...

  11. Brain white matter microstructure is associated with susceptibility to motion-induced nausea

    Napadow, Vitaly J.; Sheehan, J.; Kim, Jieun; Dassatti, Allison; Thurler, Andrea H.; Surjanhata, Brian; Vangel, Mark G.; Makris, Nikolaos; Schaechter, Judith Diane; Kuo, Braden
    Nausea is associated with significant morbidity, and there is a wide range in the propensity of individuals to experience nausea. The neural basis of this heterogeneity in nausea susceptibility is poorly understood. Our previous functional magnetic resonance imaging (fMRI) study in healthy adults showed that a visual motion stimulus caused activation in the right MT+/V5 area, and that increased sensation of nausea due to this stimulus was associated with increased activation in the right anterior insula. For the current study, we hypothesized that individual differences in visual motion-induced nausea are due to microstructural differences in the inferior fronto-occipital fasciculus (IFOF),...

  12. Disrupted Brain Circuitry for Pain-Related Reward/Punishment in Fibromyalgia

    Loggia, Marco Luciano; Berna, Chantal; Kim, Jieun; Cahalan, Christine M.; Gollub, Randy L.; Wasan, Ajay D.; Harris, Richard E.; Edwards, Robert R; Napadow, Vitaly J.
    Objective While patients suffering from fibromyalgia (FM) are known to exhibit hyperalgesia, the central mechanisms contributing to this altered pain processing are not fully understood. In this study we investigate potential dysregulation of the neural circuitry underlying cognitive and hedonic aspects of the subjective experience of pain such as anticipation of pain and of pain relief. Methods FMRI was performed on 31 FM patients and 14 controls while they received cuff pressure pain stimuli on their leg, calibrated to elicit a pain rating of ∼50/100. During the scan, subjects also received visual cues informing them of impending pain onset (pain anticipation) and pain...

  13. Does androgen insufficiency cause lacrimal gland inflammation and aqueous tear deficiency?

    Sullivan, David A.; Krenzer, Kathleen; Sullivan, Benjamin; Tolls, Dorothy Bazzinotti; Toda, Ikuko; Dana, M. Reza
    PURPOSE: The current investigators have shown that androgen treatment suppresses inflammation and stimulates the function of lacrimal glands in mouse models of Sjögren's syndrome. Recently, others have hypothesized that androgen insufficiency induces an autoimmune process in lacrimal tissue, leading to inflammation, a Sjögren's syndrome-like pathology, and aqueous tear deficiency. The purpose of the present study was to test this hypothesis. METHODS: Lacrimal glands were obtained from adult testicular feminized (Tfm) and control mice; castrated rats, guinea pigs, and rabbits; and castrated rats without anterior or whole pituitary glands and were processed for histology and image analysis. Tear volumes were measured...

  14. Hoxa9 Immortalizes a Granulocyte-Macrophage Colony-Stimulating Factor-Dependent Promyelocyte Capable of Biphenotypic Differentiation to Neutrophils or Macrophages, Independent of Enforced Meis Expression

    Calvo, Katherine R.; Kamps, Mark P.; Pasillas, Martina; Sykes, David Brian
    The genes encoding Hoxa9 and Meis1 are transcriptionally coactivated in a subset of acute myeloid leukemia (AML) in mice. In marrow reconstitution experiments, coexpression of both genes produces rapid AML, while neither gene alone generates overt leukemia. Although Hoxa9 and Meis1 can bind DNA as heterodimers, both can also heterodimerize with Pbx proteins. Thus, while their coactivation may result from the necessity to bind promoters as heterodimers, it may also result from the necessity of altering independent biochemical pathways that cooperate to generate AML, either as monomers or as heterodimers with Pbx proteins. Here we demonstrate that constitutive expression of...

  15. The HoxB1 hexapeptide is a prefolded domain: Implications for the Pbx1/Hox interaction

    Slupsky, Carolyn M.; Sykes, David Brian; Gay, Grant L.; Sykes, Brian D.
    Hox proteins are transcriptional regulators that bind consensus DNA sequences. The DNA-binding specificity of many of these Hox proteins is modulated by the heterodimerization with partners, such as the Pbx proteins. This cooperative heterodimerization is accomplished through a conserved hexapeptide motif found N-terminal to the Hox DNA-binding homeodomain. Several human leukemias have been associated with a chromosomal translocation involving either the Hox gene (i.e., NUP98/HOXA9) or the gene encoding Pbx1 (E2A/PBX1). The transforming ability of these fusion oncoproteins relies at least partially on the ability to interact with one another through this hexapeptide motif. Herein we describe NMR structural calculations...

  16. Meis1a suppresses differentiation by G-CSF and promotes proliferation by SCF: Potential mechanisms of cooperativity with Hoxa9 in myeloid leukemia

    Calvo, K. R.; Knoepfler, P. S.; Sykes, David Brian; Pasillas, M. P.; Kamps, M. P.
    Hoxa9 and Meis1a are homeodomain transcription factors that heterodimerize on DNA and are down-regulated during normal myeloid differentiation. Hoxa9 and Meis1a cooperate to induce acute myeloid leukemia (AML) in mice, and are coexpressed in human AML. Despite their cooperativity in leukemogenesis, we demonstrated previously that retroviral expression of Hoxa9 alone—in the absence of coexpressed retroviral Meis1 or of expression of endogenous Meis genes—blocks neutrophil and macrophage differentiation of primary myeloid progenitors cultured in granulocyte–macrophage colony-stimulating factor (GM-CSF). Expression of Meis1 alone did not immortalize any factor-dependent marrow progenitor. Because HoxA9-immortalized progenitors still execute granulocytic differentiation in response to granulocyte CSF...

  17. An Induced Ets Repressor Complex Regulates Growth Arrest during Terminal Macrophage Differentiation

    Klappacher, Günter W.; Lunyak, Victoria V.; Sykes, David Brian; Sawka-Verhelle, Dominique; Sage, Julien; Brard, Gyan; Ngo, Sally D.; Gangadharan, Denise; Jacks, Tyler; Kamps, Mark P.; Rose, David W.; Rosenfeld, Michael G.; Glass, Christopher K.
    Defining the molecular mechanisms that coordinately regulate proliferation and differentiation is a central issue in development. Here, we describe a mechanism in which induction of the Ets repressor METS/PE1 links terminal differentiation to cell cycle arrest. Using macrophages as a model, we provide evidence that METS/PE1 blocks Ras-dependent proliferation without inhibiting Ras-dependent expression of cell type-specific genes by selectively replacing Ets activators on the promoters of cell cycle control genes. Antiproliferative effects of METS require its interaction with DP103, a DEAD box-containing protein that assembles a novel corepressor complex. Functional interactions between the METS/DP103 complex and E2F/ pRB family proteins...

  18. TH2 Cytokines and Allergic Challenge Induce Ym1 Expression in Macrophages by a STAT6-dependent Mechanism

    Welch, John Crawford; Escoubet-Lozach, Laure; Sykes, David Brian; Liddiard, Kate; Greaves, David R.; Glass, Christopher K.
    The diverse functions of macrophages as participants in innate and acquired immune responses are regulated by the specific milieu of environmental factors, cytokines, and other signaling molecules that are encountered at sites of inflammation. Microarray analysis of the transcriptional response of mouse peritoneal macrophages to the TH2 cytokine interleukin-4 (IL-4) identified Ym1 and arginase as the most highly up-regulated genes, exhibiting more than 68- and 88-fold induction, respectively. Molecular characterization of the Ym1 promoter in transfected epithelial and macrophage cell lines revealed the presence of multiple signal transducers and activators of transcription 6 (STAT6) response elements that function in a...

  19. E2a/Pbx1 Induces the Rapid Proliferation of Stem Cell Factor-Dependent Murine Pro-T Cells That Cause Acute T-Lymphoid or Myeloid Leukemias in Mice

    Sykes, David Brian; Kamps, Mark P.
    Oncoprotein E2a/Pbx1 is produced by the t(1;19) chromosomal translocation of human pre-B acute lymphoblastic leukemia. E2a/Pbx1 blocks differentiation of primary myeloid progenitors but, paradoxically, induces apoptosis in established pre-B-cell lines, and no transforming function of E2a/Pbx1 has been reported in cultured lymphoid progenitors. Here, we demonstrate that E2a/Pbx1 induces immortal proliferation of stem cell factor (SCF)-dependent pro-T thymocytes by a mechanism dependent upon both its transactivation and DNA-binding functions. E2a-Pbx1 cooperated with cytokines or activated signaling oncoproteins to induce cell division, as inactivation of conditional E2a/Pbx1 in either factor-dependent pro-T cells or pro-T cells made factor independent by expression of...

  20. The TEMPI Syndrome — A Novel Multisystem Disease

    Sykes, David Brian; Schroyens, Wilfried; O'Connell, Casey

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