RESUMO
Cellular senescence is a stress response mechanism that induces proliferative arrest. Hypoxia can bypass senescence and extend the lifespan of primary cells, mainly by decreasing oxidative damage. However, how hypoxia promotes these effects prior to malignant transformation is unknown. Here we observed that the lifespan of mouse embryonic fibroblasts (MEFs) is increased when they are cultured in hypoxia by reducing the expression of p16INK4a, p15INK4b and p21Cip1. We found that proliferating MEFs in hypoxia overexpress Tfcp2l1, which is a main regulator of pluripotency and self-renewal in embryonic stem cells, as well as stemness genes including Oct3/4, Sox2 and Nanog. Tfcp2l1 expression is lost during culture in normoxia, and its expression in hypoxia is regulated by Hif1α. Consistently, its overexpression in hypoxic levels increases the lifespan of MEFs and promotes the overexpression of stemness genes. ATAC-seq and Chip-seq experiments showed that Tfcp2l1 regulates genes that control proliferation and stemness such as Sox2, Sox9, Jarid2 and Ezh2. Additionally, Tfcp2l1 can replicate the hypoxic effect of increasing cellular reprogramming. Altogether, our data suggest that the activation of Tfcp2l1 by hypoxia contributes to immortalization prior to malignant transformation, facilitating tumorigenesis and dedifferentiation by regulating Sox2, Sox9, and Jarid2.
Assuntos
Senescência Celular , Fibroblastos , Animais , Camundongos , Carcinogênese/patologia , Transformação Celular Neoplásica/metabolismo , Células Cultivadas , Fibroblastos/metabolismo , Hipóxia/metabolismoRESUMO
Schizophrenia is associated with alterations in working memory that reflect dysfunction of dorsolateral prefrontal cortex (DLPFC) circuitry. Working memory depends on the activity of excitatory pyramidal cells in DLPFC layer 3 and, to a lesser extent, in layer 5. Although many studies have profiled gene expression in DLPFC gray matter in schizophrenia, little is known about cell-type-specific transcript expression in these two populations of pyramidal cells. We hypothesized that interrogating gene expression, specifically in DLPFC layer 3 or 5 pyramidal cells, would reveal new and/or more robust schizophrenia-associated differences that would provide new insights into the nature of pyramidal cell dysfunction in the illness. We also sought to determine the impact of other variables, such as a diagnosis of schizoaffective disorder or medication use at the time of death, on the patterns of gene expression in pyramidal neurons. Individual pyramidal cells in DLPFC layers 3 or 5 were captured by laser microdissection from 36 subjects with schizophrenia or schizoaffective disorder and matched normal comparison subjects. The mRNA from cell collections was subjected to transcriptome profiling by microarray followed by quantitative PCR validation. Expression of genes involved in mitochondrial (MT) or ubiquitin-proteasome system (UPS) functions were markedly downregulated in the patient group (P-values for MT-related and UPS-related pathways were <10(-7) and <10(-5), respectively). MT-related gene alterations were more prominent in layer 3 pyramidal cells, whereas UPS-related gene alterations were more prominent in layer 5 pyramidal cells. Many of these alterations were not present, or found to a lesser degree, in samples of DLPFC gray matter from the same subjects, suggesting that they are pyramidal cell specific. Furthermore, these findings principally reflected alterations in the schizophrenia subjects were not present or present to a lesser degree in the schizoaffective disorder subjects (diagnosis of schizoaffective disorder was the most significant covariate, P<10(-6)) and were not attributable to factors frequently comorbid with schizophrenia. In summary, our findings reveal expression deficits in MT- and UPS-related genes specific to layer 3 and/or layer 5 pyramidal cells in the DLPFC of schizophrenia subjects. These cell type-specific transcriptome signatures are not characteristic of schizoaffective disorder, providing a potential molecular-cellular basis of differences in clinical phenotypes.
Assuntos
Regulação da Expressão Gênica/fisiologia , Córtex Pré-Frontal/patologia , Transtornos Psicóticos/patologia , Células Piramidais/metabolismo , Esquizofrenia/patologia , Transcriptoma/fisiologia , Adulto , Análise de Variância , Animais , Antipsicóticos/farmacologia , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Microdissecção e Captura a Laser , Macaca fascicularis , Masculino , Pessoa de Meia-Idade , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Córtex Pré-Frontal/efeitos dos fármacos , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Ubiquitina/genética , Ubiquitina/metabolismoRESUMO
INTRODUCCIÓN: La Aspergilosis broncopulmonar alérgica es una enfermedad poco frecuente con prevalencia de 1 a 2 por ciento a nivel mundial. Se diagnostica según Infectious Diseases Society of America por: episodios de obstrucción bronquial, eosinofilia periférica, test de reactividad cutánea a antígeno de Aspergillus, precipitación de anticuerpos para el antígeno de Aspergillus, elevación de IgE en suero, historia de infiltrados pulmonares y bronquiectasias centrales. Puede atravesar estadios de asmaaguda sensible a corticosteroides hasta estadios finales de fibrosis pulmonar. PRESENTACIÓN DEL CASO: Joven de 22 años acude al Instituto de Previsión Social, Hospital Central en la ciudad de Asunción, en donde es internado por malestar general, tos con expectoración amarillenta, sibilancias, sensación febril y dificultad respiratoria, con diagnóstico de ingreso de neumonía adquirida en la comunidad y enfermedad tipo influenza, que responde al tratamiento sintomático. Se practica una radiografía simple de tórax donde se observa un patrón algodonoso bilateral. Un mes después, acude de nuevo al Hospital Central por persistencia del cuadro con eosinofilia periférica de 60 por ciento, frotis de heces sin reporte de parásitos, IgE total en suero 530 KIU/L, tomografía axial computarizada con infiltrado pulmonar difuso bilateral, test de reactividad cutánea a antígeno de Aspergillus positivo y precipitación de anticuerpos para el antígeno de Aspergillus positivo. Se trató con prednisona e itraconazol por 16semanas, obteniéndose buena respuesta; tres meses después de suspender el tratamiento no manifiesta síntomas. DISCUSIÓN: Ante pacientes internados por cuadros respiratorios presistentes es necesario un diagnóstico temprano y adecuado con el objetivo de evitar secuelas posteriores.
INTRODUCTION: Allergic Bronchopulmonary Aspergillosisis a rare disease with a prevalence of 1 to 2 percent worldwide. It is diagnosed according to the Infectious Diseases Society of America by: episodes of bronchial obstruction, peripheral eosinophilia, positive skin-prick test to Aspergillus antigen, precipitating antibodies to Aspergillus antigen, elevated serum IgE, history of pulmonary infiltrates and central bronchiectasis. It can go through stages of corticosteroid-sensitive acute asthma to end-stage pulmonary fibrosis. CASE REPORT: A 22 year old man goes to Instituto de Prevision Social, Hospital Central de Asuncion, where is hospitalized accompanied by general malaise, cough with yellow sputum, wheezing, feverish feeling andshortness of breath, with admission diagnosis of Community Acquired Pneumonia and influenza-like illness that responds to symptomatic treatment. Chest radiography shows a bilateral cottony pattern. A month later, a persistence of the symptoms is observed with 60 percent peripheral eosinophilia, faeces smear is reported without parasites, total serum IgE 530 KIU / L chest, computed tomography with diffuse bilateral pulmonary infiltrates, positive skin antigen reactivity test for Aspergillus, positive precipitating antibodies to Aspergillus species. He was treated with prednisone and itraconazole for 16 weeks, with good response. Three months after treatment there are no symptoms. DISCUSSION: Patients hospitalized for persistently respiratory symptoms, early diagnosis is necessary and appropriate in order to prevent sequelae.
Assuntos
Humanos , Masculino , Adulto , Aspergilose Broncopulmonar Alérgica/diagnóstico , Aspergilose Broncopulmonar Alérgica/tratamento farmacológico , Aspergillus fumigatus , Antibacterianos/uso terapêutico , Eosinofilia , Imunoglobulina ERESUMO
There is widespread recognition that consistency between research centres in the ways that patients with tinnitus are assessed and outcomes following interventions are measured would facilitate more effective co-operation and more meaningful evaluations and comparisons of outcomes. At the first Tinnitus Research Initiative meeting held in Regensburg in July 2006 an attempt was made through workshops to gain a consensus both for patient assessments and for outcome measurements. It is hoped that this will contribute towards better cooperation between research centres in finding and evaluating treatments for tinnitus by allowing better comparability between studies.
Assuntos
Inquéritos e Questionários/normas , Zumbido/diagnóstico , Zumbido/terapia , Consenso , Humanos , Resultado do TratamentoRESUMO
The aim of the study was to assess the role of non-operative treatment in haemodynamically stable patients with liver trauma. Over the period from 1996 to July 2000, out of a total of 2,048 patients with abdominal trauma, 124 open and 1,924 closed, we observed 77 hepatic lesions, consisting of 55 closed traumas and 22 penetrating traumas. Non-operative treatment was implemented in 18 patients (32.7%) with closed liver traumas. In addition to serial clinical examinations of the abdomen, the patients receiving non-operative treatment were submitted to thorough haemodynamic monitoring and complete blood counts in the intensive care unit. After an abdominal CT scan at entry, patients were submitted to abdominal ultrasonography 6, 12 and 24 hours after admission. Only two patients required transfusions, one presenting a pelvic fracture and the other a triple fracture of the femur, tibia and fibula. There was no mortality. A biloma was present in one case, successfully treated by means of a US-guided drainage puncture. It is patients with major cranial traumas that pose most problems for conservative treatment. Fifty percent of non-therapeutic laparotomies in our series were performed in patients with severe cranial traumas. It is precisely in these patients that an improvement in diagnostic capability is most desirable.
Assuntos
Fígado/lesões , Ferimentos não Penetrantes/terapia , Ferimentos Penetrantes/terapia , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The Authors conducted a retrospective study on 98 patients with intestinal infarction observed from 1987 to 1999 in the Emergency Care Unit of the Loreto Hospital, Naples. In our hospital there are over 20,000 admissions, 3,900 of whom in the Emergency Care Unit. Intestinal infarction accounts for 0.049% of all admissions and 0.45% of emergency surgery admissions. About 500 laparotomies are performed annually, 1% of which for intestinal infarction. All patients in this series were operated on within 10 hours of admission. The following procedures were performed: 31 jejuno-ileal resections; 26 right hemicolectomies associated with small intestine resection; 5 upper mesenteric artery embolectomies plus wide gut resections (3 also underwent second-look operations within 36 hours of the initial surgery with further gut resection); 1 Hartmann's and 5 Volkmann's operations (all of these patients had colonic gangrene); 30 (30.5%) underwent exploratory laparotomy due to massive infarction. The prognosis of intestinal infarction is still ominous. Our mortality rate is 68%. Both clinical and laboratory data are non-specific and delayed diagnosis is the main cause of this mortality rate. Abdominal CT is an accurate and sensitive diagnostic tool. TPN enables us to achieve good nutritional support even for wider resections.
Assuntos
Infarto/cirurgia , Intestinos/irrigação sanguínea , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
PURPOSE: To correlate the absence of distortion-product otoacoustic emissions observed in sudden hearing loss (SHL) with a possible thromboembolic vascular cause, using an animal model. BACKGROUND: Distortion-product otoacoustic emissions (DPOAEs) are sensitive to cochlear disorders and are absent in cochlear injury. In a previous study, the authors showed that 75% of patients with SHL who have no measurable emissions do not recover hearing. The underlying cause of the loss of emissions is unknown, but it may be secondary to cochlear ischemia. METHODS: Six New Zealand white rabbits underwent unilateral cochlear embolization through the use of circulating iron particles under magnetic control. Cochlear function was monitored through DPOAE recordings of the experimental and control ears. RESULTS: In all animals, a rapid decrease in emissions was noted, which fluctuated but returned to baseline within 2 hours to 3 weeks after embolization, leaving no measurable residual defects. The DPOAEs were suppressed by 5 to 19 dB within 10 minutes of injection of iron solution and magnet placement. The lowest emissions were obtained at 30 minutes and again at 120 minutes, which were 12 to 37 dB below preembolization levels. Two animals returned to baseline DPOAE levels at 1 to 3 weeks, with no identifiable residual deficits. CONCLUSION: It is likely that the loss of emissions seen in the present study is related to cochlear ischemia. The early suppression of DPOAEs in the rabbit cochlea after embolization may parallel that in SHL patients with absence of DPOAEs on presentation.
Assuntos
Cóclea/irrigação sanguínea , Cóclea/metabolismo , Modelos Animais de Doenças , Perda Auditiva Súbita/etiologia , Ferro/farmacocinética , Isquemia/complicações , Isquemia/metabolismo , Magnetismo , Animais , Emissões Otoacústicas Espontâneas/fisiologia , Coelhos , Fatores de TempoRESUMO
Kinase suppressor of Ras (KSR) is an evolutionarily conserved component of Ras-dependent signaling pathways. Here, we report the identification of B-KSR1, a novel splice variant of murine KSR1 that is highly expressed in brain-derived tissues. B-KSR1 protein is detectable in mouse brain throughout embryogenesis, is most abundant in adult forebrain neurons, and is complexed with activated mitogen-activated protein kinase (MAPK) and MEK in brain tissues. Expression of B-KSR1 in PC12 cells resulted in accelerated nerve growth factor (NGF)-induced neuronal differentiation and detectable epidermal growth factor (EGF)-induced neurite outgrowth. Sustained MAPK activity was observed in cells stimulated with either NGF or EGF, and all effects on neurite outgrowth could be blocked by the MEK inhibitor PD98059. In B-KSR1-expressing cells, the MAPK-B-KSR1 interaction was inducible and correlated with MAPK activation, while the MEK-B-KSR1 interaction was constitutive. Further examination of the MEK-B-KSR1 interaction revealed that all genetically identified loss-of-function mutations in the catalytic domain severely diminished MEK binding. Moreover, B-KSR1 mutants defective in MEK binding were unable to augment neurite outgrowth. Together, these findings demonstrate the functional importance of MEK binding and indicate that B-KSR1 may function to transduce Ras-dependent signals that are required for neuronal differentiation or that are involved in the normal functioning of the mature central nervous system.
Assuntos
Encéfalo/metabolismo , MAP Quinase Quinase Quinase 1 , Neurônios/metabolismo , Proteínas Quinases/metabolismo , Transdução de Sinais , Tirosina 3-Mono-Oxigenase , Proteínas 14-3-3 , Trifosfato de Adenosina/metabolismo , Processamento Alternativo , Sequência de Aminoácidos , Animais , Domínio Catalítico , Diferenciação Celular , Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Humanos , Camundongos , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Dados de Sequência Molecular , Mutação , Especificidade de Órgãos , Células PC12 , Isoformas de Proteínas , Proteínas Quinases/genética , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas/metabolismo , Ratos , Proteínas ras/metabolismoRESUMO
Functional imaging based on magnetic resonance methods is a new research frontier for exploring a wide range of central nervous system (CNS) functions, including information processing in sensory, motor, cognitive, and linguistic systems. Being able to localize and study human brain function in vivo, in relatively high resolution and in a noninvasive manner, makes this a technique of unparalleled importance. In order to appreciate and fully understand this area of investigation, a tutorial covering basic aspects of this methodology is presented. We introduce functional magnetic resonance imaging (fMRI) by providing an overview of the studies of different sensory systems in response to modality-specific stimuli, followed by an outline of other areas that have potential clinical relevance to the medical, cognitive, and communicative sciences. The discussion then focuses on the basic principles of magnetic resonance methods including magnetic resonance imaging, MR spectroscopy, fMRI, and the potential role that MR technology may play in understanding a wide range of auditory functions within the CNS, including tinnitus-related activity. Because the content of the material found herein might be unfamiliar to some, we provide a broad range of background and review articles to serve as a technical resource.
Assuntos
Audiometria , Orelha/anatomia & histologia , Imageamento por Ressonância Magnética , Neurociências , Corpo Estriado/anatomia & histologia , História do Século XX , Humanos , Imageamento por Ressonância Magnética/história , FísicaRESUMO
OBJECTIVE: To evaluate the feasibility of universal newborn hearing screening by examining inpatient outcome measures from 8 hospitals located in geographically diverse areas of New York State over a 3-yr period. DESIGN: Funding was provided by the New York State Department of Health to implement predischarge hearing screening programs in the neonatal intensive care units (NICUs) and well-baby nurseries (WBNs) of eight hospitals. Various screening protocols including transient evoked otoacoustic emissions alone or in combination with conventional auditory brain stem response or screening auditory brain stem response were implemented by each site. Measured outcomes included rate of misses, refusals, and fails. Results were analyzed as a function of year of operation, nursery type, and geographic location. RESULTS: Six out of eight hospitals successfully implemented universal hearing screening during the first year, and the remaining 2 hospitals implemented programs during the second year of the project. Over a period of 3 yr, 69,761 newborns were screened at the eight hospitals representing 96.9% of all live births. The overall fail rate (4.04%) combined with the miss rate (2.61%) resulted in 6.63% of infants referred for outpatient follow-up. Mean data indicated that inpatient outcome measures improved with year of operation, with most individual hospitals also showing improvements. Both fail and miss rates were higher in the NICU than in the WBN and for hospitals located in New York City than in other regions of the state. CONCLUSIONS: Inpatient outcome measures of a universal newborn hearing screening project, which involved multiple centers across geographically diverse regions of New York State, were acceptable in terms of successfully screening a high percentage of live births and attaining low refer rates for outpatient screening. This study adds to the growing body of literature supporting the feasibility of screening all newborns before hospital discharge.
Assuntos
Transtornos da Audição/epidemiologia , Triagem Neonatal , Estimulação Acústica/métodos , Cóclea/fisiopatologia , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Estudos de Viabilidade , Seguimentos , Transtornos da Audição/diagnóstico , Transtornos da Audição/fisiopatologia , Hospitais , Humanos , Recém-Nascido , New York/epidemiologia , Emissões Otoacústicas Espontâneas/fisiologiaRESUMO
OBJECTIVE: To determine the ages of hearing loss identification, hearing aid fitting, and enrollment in early intervention through a multi-center, state-wide universal newborn hearing screening project. DESIGN: Universal newborn hearing screening was conducted at eight hospitals across New York State. All infants who did not bilaterally pass hearing screening before discharge were recalled for outpatient retesting. Inpatient screening and outpatient rescreening were done with transient evoked otoacoustic emissions and/or auditory brain stem response testing. Diagnostic testing was performed with age appropriate tests, auditory brain stem response and/or visual reinforcement audiometry. Infants diagnosed with permanent hearing loss were considered for hearing aids and early intervention. Ages of hearing loss identification, hearing aid fitting, and enrollment in early intervention were investigated regarding nursery type, risk status, unilateral versus bilateral hearing loss, loss type, loss severity, and state regions. RESULTS: The prevalence of infants diagnosed with permanent hearing loss was 2.0/1000 (85 of 43,311). Of the 85 infants with hearing loss, 61% were from neonatal intensive care units (NICUs) and 67% were at risk for hearing loss. Of the 36 infants fitted with hearing aids, 58% were from NICUs and 78% were at risk for hearing loss. The median age at identification and enrollment in early intervention was 3 mo. Median age at hearing aid fitting was 7.5 mo. Median ages at identification were less for infants from the well-baby nurseries (WBNs) than for the NICU infants and for infants with severe/profound than for infants with mild/moderate hearing loss, but were similar for not-at-risk and at-risk infants. Median ages at hearing aid fitting were less for well babies than for NICU infants, for not-at-risk infants than for at-risk infants, and for infants with severe/ profound hearing loss than for infants with mild/ moderate hearing loss. However, median ages at early intervention enrollment were similar for nursery types, risk status, and severity of hearing loss. CONCLUSIONS: Early ages of hearing loss identification, hearing aid fitting, and enrollment in early intervention can be achieved for infants from NICUs and WBNs and for infants at risk and not at risk for hearing loss in a large multi-center universal newborn hearing screening program.
Assuntos
Auxiliares de Audição , Transtornos da Audição/epidemiologia , Transtornos da Audição/terapia , Triagem Neonatal , Ajuste de Prótese , Fatores Etários , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Transtornos da Audição/diagnóstico , Humanos , Lactente , Recém-Nascido , New York/epidemiologia , Prevalência , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: To investigate outpatient outcome measures of a multi-center, state-wide, universal newborn hearing screening project. DESIGN: Eight hospitals participated in a 3-yr, funded project. Each hospital designed its own protocol using common criteria for judging whether an infant passed a hearing screening. Infants were tested in the hospital, and those either failing the in-hospital screening or who were not tested in the hospital (missed) were asked to return 4 to 6 wk after hospital discharge for outpatient rescreening. Those infants failing the outpatient rescreening were referred for diagnostic auditory brain stem response testing. Each hospital used its own audiological equipment and criteria to determine whether a particular infant had a hearing loss. All data were collected and analyzed for individual hospitals, as well as totaled across all hospitals. Data were analyzed in terms of year of program operation, nursery type, and geographic region. RESULTS: Seventy-two percent of infants who failed the in-hospital screening returned for outpatient testing. The percentage of in-hospital fails returning for retesting was significantly higher than the percentage of in-hospital misses returning for retesting. The percentage of infants returning for retesting increased with successive years of program operation. Some differences were noted in the percentage of infants returning for retesting among hospitals and geographic regions of the state. Some differences in outpatient outcome measures also were noted between infants originally born into the neonatal intensive care unit (NICU) and the well-baby nursery (WBN). The percentage of infants from the NICU who returned for retesting was slightly higher than that for infants from the WBN. The percentage of infants from the WBN passing the outpatient rescreening was higher than that for the NICU infants. The overall prevalence of hearing loss was 1.96/1000, with that in the NICU being 8/1000 and that in the WBN being 0.9/1000. Positive predictive value for permanent hearing loss based on inpatient screening was approximately 4% and based on outpatient rescreening was approximately 22%. CONCLUSIONS: Several outpatient outcome measures changed with successive years of program operation, suggesting that programs improve over time. Also, some outpatient outcome measures differ between NICU and WBN populations. The differences noted across regions of the state in the percentage of infants returning for outpatient retesting require further research to determine whether differences are due to demographic and/or procedural differences.
Assuntos
Transtornos da Audição/epidemiologia , Triagem Neonatal , Assistência Ambulatorial , Seguimentos , Transtornos da Audição/diagnóstico , Humanos , Recém-Nascido , New York/epidemiologia , Valor Preditivo dos Testes , PrevalênciaRESUMO
OBJECTIVE: To examine differences among various test protocols on the fail rate at hospital discharge for infants in the well-baby nursery (WBN) and neonatal intensive care unit (NICU) who received hearing screening through a universal newborn hearing screening demonstration project. DESIGN: The outcomes of several screening protocols were examined. Two technologies were used: transient evoked otoacoustic emissions (TEOAEs) alone or in combination with the auditory brain stem response (ABR). The performance of test protocols in both nurseries within eight hospitals was examined over a 2- to 3-yr period. In the WBN, six hospitals used a screening protocol of TEOAE technology first followed by an ABR (automated or conventional) technology screening for newborns who referred on TEOAE screening. Two hospitals used TEOAE only in the WBN. Seven hospitals used screening protocols in the NICU that used a combination of TEOAE and ABR technologies (TEOAE technology administered first or second, before or after TEOAE, or TEOAE and ABR tests on all infants). Only one hospital used TEOAE technology exclusively for hearing screening. RESULTS: Significant differences among screening protocols were found across hospitals in the first, second, and third years of the program. The combination of TEOAE technology and ABR technology (a two-technology screening protocol) resulted in a significantly lower fail rate at hospital discharge than the use of a single-technology (TEOAE). Fail rates at discharge were twice as high using the one-technology protocol versus two-technology protocol, even when the best outcomes from program year 3 were considered exclusively. Results of two-technology versus one-technology protocols were similar in the NICU. Use of a second technology for screening TEOAE fails significantly reduced every hospital that used the protocol's fail rate at discharge. CONCLUSIONS: A two-technology screening protocol resulted in significantly lower fail rates at hospital discharge in both the WBN and NICU nurseries than use of a single-technology (TEOAE) hearing screening protocol.
Assuntos
Transtornos da Audição/epidemiologia , Triagem Neonatal , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Seguimentos , Transtornos da Audição/diagnóstico , Hospitais , Humanos , Recém-Nascido , New York/epidemiologiaRESUMO
There is considerable interest in whether a deficit in temporal processing underlies specific learning and language disabilities in school-aged children. This view is particularly controversial in the area of developmental reading problems. The temporal-processing hypothesis was tested in a sample of normal children, 9-11 years of age, and in a sample of age-matched children with reading impairments, by assessing temporal-order discrimination. Five different binary temporal-order tasks were evaluated in the auditory and visual sensory modalities. Other basic discrimination abilities for single auditory stimuli were also assessed, including just noticeable differences (JNDs) for frequency and intensity and a simple threshold detection task. In these tasks, the temporal dimension was the duration of the individual stimuli (20 and 200 ms). All data were obtained using forced- choice psychophysical methods, either in a single-track adaptive format or using psychometric functions. The results from these experiments showed that children with reading impairments had deficits in temporal-order discrimination, but these effects were not modality specific. These same children also had significantly elevated frequency and intensity JNDs and their performance on these tasks were not dependent on stimulus duration. No group differences were observed on the threshold detection task, and the derived measurements of temporal integration (i.e. the threshold difference between the 20- and 200-ms stimuli) were considered normal, averaging 11.7 dB. As a whole, discrimination deficits observed in the reading-impaired group only occurred with suprathreshold stimuli. The deficits were neither modality specific nor temporal (duration) specific.
Assuntos
Dislexia/terapia , Transtornos da Percepção/diagnóstico , Ensino de Recuperação , Percepção do Tempo/fisiologia , Percepção Auditiva/fisiologia , Criança , Feminino , Humanos , Masculino , Resultado do Tratamento , Percepção Visual/fisiologiaRESUMO
Cutaneous-evoked tinnitus is a clinical entity that has not been reported previously in the neurootological literature. Herein, a neuroscience framework that encompasses several distinct areas of research is used to conceptualize and help understand this phenomenon. We review normal neuroanatomical and physiological interactions between auditory and somatosensory systems in mammals. Also considered are mechanistic accounts of lesion-induced changes in the CNS following deafferentation/deefferentation of peripheral sensory or motor structures that may have a relationship to this phenomenon, as well as the role of functional imaging modalities in studying various phantom perceptions.
Assuntos
Zumbido/etiologia , Tato , Encéfalo/anatomia & histologia , Sistema Nervoso Central/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Estimulação Física/efeitos adversos , Córtex Somatossensorial , Vestíbulo do Labirinto/fisiologiaRESUMO
DC00166e and acute unilateral deafferentation of the auditory periphery (auditory and vestibular afferents) can induce changes in the central nervous system that may result in unique forms of tinnitus. These tinnitus perceptions can be controlled (turned on and off) or modulated (changed in pitch or loudness) by performing certain overt behaviors in other sensory/motor systems. Clinical reports from our laboratory and several other independent sources indicate that static change in eye gaze, from a neutral head-referenced position, is one such behavior that can evoke, modulate and/or suppress these phantom auditory events. This report deals with a new clinical entity and a form of tinnitus that can be evoked directly by cutaneous stimulation of the upper hand and fingertip regions. In 2 adults, cutaneous-evoked tinnitus was reported following neurosurgery for space-occupying lesions at the base of the skull and posterior craniofossa, where hearing and vestibular functions were lost completely and acutely in one ear (unilateral deafferentation) and facial nerve paralysis (unilateral deefferentation) was present either immediately following neurosurgery or had occurred as a delayed-onset event. Herein, we focus on the phenomenology of this discovery, provide perceptual correlates using contemporary psychophysical methods and document in one individual cutaneous-evoked tinnitus-related neural activity using functional magnetic resonance imaging. In a companion paper, neuroanatomical and physiological interactions between auditory and somatosensory systems, possible mechanistic accounts and relevant functional neuroimaging studies are reviewed.
Assuntos
Encéfalo/diagnóstico por imagem , Estimulação Física/efeitos adversos , Zumbido/diagnóstico , Zumbido/etiologia , Tato , Idoso , Neoplasias dos Nervos Cranianos/complicações , Neoplasias dos Nervos Cranianos/patologia , Neoplasias dos Nervos Cranianos/cirurgia , Feminino , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/etiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neurilemoma/complicações , Neurilemoma/patologia , Neurilemoma/cirurgia , Estimulação Luminosa/efeitos adversos , Psicofísica , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Nervo Vestibular/patologia , Nervo Vestibular/cirurgiaRESUMO
A case of 'central deafness' is presented in a 3-year-old male Caucasian child with Moyamoya disease (MMD); a rare, progressive and occlusive cerebrovascular disorder predominantly affecting the carotid artery system. Documentation of normal peripheral auditory function and brainstem pathway integrity is provided by acoustic admittance, otoacoustic emission and brainstem auditory evoked potential measurements. The lack of behavioral response to sound, and absent middle and long latency auditory evoked potentials suggest thalamo-cortical dysfunction. Magnetic resonance imaging showed diffuse ischemic damage in subcortical white matter including areas of the temporal lobes. In addition, there were multiple and focal cortical infarctions in both cerebral hemispheres, focused primarily in the frontal, parietal and temporal areas. Taken together, these structural and functional abnormalities in addition to severely delayed speech and language development are consistent with the diagnosis of central deafness and suggest a disconnection between higher brainstem and cortical auditory areas. The child's father also has MMD, but was diagnosed only recently. The presence of paternal linkage is informative since it rules out x-linked recessive and maternal inheritance. To our knowledge, this represents the first documented case of paternal linkage in MMD with central deafness in a Caucasian child with no apparent Japanese ancestry. Herein, we focus on central auditory dysfunction and consider how lesion-induced changes have contributed to a deficit in basic auditory responsiveness, including a severe disturbance in receptive and expressive auditory-based speech and language skills.
Assuntos
Doenças Auditivas Centrais/complicações , Pai , Ligação Genética/genética , Doença de Moyamoya/complicações , Doença de Moyamoya/genética , Adulto , Córtex Auditivo/fisiopatologia , Doenças Auditivas Centrais/diagnóstico , Isquemia Encefálica/patologia , Tronco Encefálico/fisiopatologia , Angiografia Cerebral/métodos , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/fisiopatologia , Potenciais Evocados Auditivos/fisiologia , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Humanos , Lactente , Transtornos do Desenvolvimento da Linguagem/diagnóstico , Transtornos do Desenvolvimento da Linguagem/etiologia , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/fisiopatologia , Emissões Otoacústicas Espontâneas/fisiologia , Distúrbios da Fala/diagnóstico , Distúrbios da Fala/etiologia , Tálamo/fisiopatologia , População BrancaRESUMO
A prospective, non-randomized study evaluated the effects of tonsillectomy and/or adenoidectomy (T +/- A) on acoustic and perceptual aspects of vocal function. Thirty-one children, ranging in age from 4 to 15 years participated and measurements were made prior to and 3 months following surgery. Twenty-three children had T +/- A and eight had adenoidectomy alone. Quantitative acoustic measures included: laryngeal (vocal fundamental frequency, FO) and supralaryngeal characteristics of sustained vowels (F1 and F2 formants, formant bandwidths, two-dimensional measures of vowel space) and temporal properties of consonant-vowel productions (diadochokinetic syllable rates). Perceptual measures were based on samples of continuous speech, using the Buffalo voice profile (BVP) and parental interviews/questionnaires were used to evaluate other aspects of surgery (i.e. subjective speech changes, protracted pain, difficulty swallowing, bleeding, etc.). Based on ANOVA, no significant post-surgical changes were detected for the majority of acoustic speech measures studied (vocal F0, formant bandwidths, measures of vowel space or diadochokinetic rates). However, the F2 formant frequency for vowels /i/ and /a/ increased and F1 decreased for /o/ following surgery. These changes had the largest effect on the structure of vowel /i/, which became more acute and diffuse following surgery. Furthermore, of the majority of perceptual measured studied with the BVP, 92% showed no change postoperatively. However, in the category of resonance, a significant decrease in hyponasality was detected. These results demonstrate that removing soft tissue from the oropharynx has only minimal impact on quantitative or qualitative (perceptual) aspects of vocal function, when measurements are made approximately 15 weeks post surgery.
Assuntos
Adenoidectomia , Tonsilectomia , Qualidade da Voz , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/diagnóstico , Estudos Prospectivos , Acústica da Fala , Distúrbios da Voz/diagnósticoRESUMO
Genetic and biochemical studies have identified kinase suppressor of Ras (KSR) to be a conserved component of Ras-dependent signaling pathways. To better understand the role of KSR in signal transduction, we have initiated studies investigating the effect of phosphorylation and protein interactions on KSR function. Here, we report the identification of five in vivo phosphorylation sites of KSR. In serum-starved cells, KSR contains two constitutive sites of phosphorylation (Ser297 and Ser392), which mediate the binding of KSR to the 14-3-3 family of proteins. In the presence of activated Ras, KSR contains three additional sites of phosphorylation (Thr260, Thr274, and Ser443), all of which match the consensus motif (Px[S/T]P) for phosphorylation by mitogen-activated protein kinase (MAPK). Further, we find that treatment of cells with the MEK inhibitor PD98059 blocks phosphorylation of the Ras-inducible sites and that activated MAPK associates with KSR in a Ras-dependent manner. Together, these findings indicate that KSR is an in vivo substrate of MAPK. Mutation of the identified phosphorylation sites did not alter the ability of KSR to facilitate Ras signaling in Xenopus oocytes, suggesting that phosphorylation at these sites may serve other functional roles, such as regulating catalytic activity. Interestingly, during the course of this study, we found that the biological effect of KSR varied dramatically with the level of KSR protein expressed. In Xenopus oocytes, KSR functioned as a positive regulator of Ras signaling when expressed at low levels, whereas at high levels of expression, KSR blocked Ras-dependent signal transduction. Likewise, overexpression of Drosophila KSR blocked R7 photoreceptor formation in the Drosophila eye. Therefore, the biological function of KSR as a positive effector of Ras-dependent signaling appears to be dependent on maintaining KSR protein expression at low or near-physiological levels.
Assuntos
Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Proteínas Quinases/metabolismo , Proteínas/metabolismo , Tirosina 3-Mono-Oxigenase , Proteínas ras/metabolismo , Proteínas 14-3-3 , Células 3T3 , Animais , Sítios de Ligação , Linhagem Celular , Linhagem Celular Transformada , Drosophila melanogaster , Camundongos , Mutação , Fosforilação , Ligação Proteica , Proteínas Quinases/genética , Coelhos , SerinaRESUMO
Thresholds for the discrimination of temporal order were determined for selected auditory and visual stimulus dimensions in 10 normal-adult volunteers. Auditory stimuli consisted of binary pure tones varying in frequency or sound pressure level, and visual stimuli consisted of binary geometric forms varying in size, orientation, or color. We determined the effect of psychophysical method and the reliability of performance across stimulus dimensions. Using a single-track adaptive procedure, Experiment 1 showed that temporal-order thresholds (TOTs) varied with stimulus dimension, being lowest for auditory frequency, intermediate for size, orientation, and auditory level, and longest for color. Test performance improved over sessions and the profile of thresholds across stimulus dimensions had a modest reliability. Experiment 2 used a double-interleaved adaptive procedure and TOTs were similarly ordered as in Experiment 1. However, TOTs were significantly lower for initially ascending versus descending tracks. With this method, the reliability of the profile across stimulus dimensions and tracks was relatively low. In Experiment 3, psychometric functions were obtained for each of the stimulus dimensions and thresholds were defined as the interpolated 70.7% correct point. The relative ordering of TOTs was similar to those obtained in the first two experiments. Non-monotonicities were found in some of the psychometric functions, with the most prominent being for the color dimension. A cross-experiment comparison of results demonstrates that TOTs and their reliability are significantly influenced by the psychophysical method. Taken together, these results support the notion that the temporal resolution of ordered stimuli involves perceptual mechanisms specific to a given sensory modality or submodality.