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1.
J Theor Biol ; 384: 19-32, 2015 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-26277735

RESUMO

Hydromechanical brain models often involve constitutive relations which must account for soft tissue deformation and creep, together with the interstitial fluid movement and exchange through capillaries. The interaction of rather unknown mechanisms which produce, absorb, and circulate the cerebrospinal fluid within the central nervous system can further add to their complexity. Once proper models for these phenomena or processes are selected, estimation of the associated parameters could be even more challenging. This paper presents the results of a consistent, coupled poroviscoelastic modeling and characterization of the brain tissue as a dual-porosity system. The model draws from Biot's theory of poroviscoelasticity, and adopts the generalized Kelvin's rheological description of the viscoelastic tissue behavior. While the interstitial space serves as the primary porosity through which the bulk flow of the interstitial fluid occurs, a secondary porosity network comprising the capillaries and venous system allows for its partial absorption into the blood. The correspondence principle is used in deriving a time-dependent analytical solution to the proposed model. It allows for identical poroelastic formulation of the original poroviscoelastic problem in the Laplace transform space. Hydrocephalus generally refers to a class of medical conditions which share the ventricles enlargement as a common feature. A set of published data from induced hydrocephalus and follow-up perfusion of cats' brains is used for quantitative characterization of the proposed model. A selected portion of these data including the ventricular volume and rate of fluid absorption from the perfused brain, together with the forward model solution, is utilized via an inverse problem technique to find proper estimations of the model parameters. Results show significant improvement in model predictions of the experimental data. The convoluted and coupled solution results are presented through the time-dependent plots of the ventricular volume undergoing the perfusion experiment. The plots demonstrate the intricate interplay of viscous and poroelastic diffusive time scales, and their competition in reaching the steady state response of the system.


Assuntos
Encéfalo/fisiopatologia , Hidrocefalia/fisiopatologia , Modelos Neurológicos , Algoritmos , Animais , Água Corporal/metabolismo , Encéfalo/irrigação sanguínea , Capilares/fisiopatologia , Gatos , Elasticidade , Humanos , Porosidade , Reologia , Viscosidade
2.
J Neurosurg ; 136(2): 575-583, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34298518

RESUMO

Neurosurgery at the University of Oklahoma has played a pivotal role in the development of the specialty in the state. Its history spans nearly 90 years, beginning in 1931 when Dr. Harry Wilkins established the first neurosurgical practice in the state at the University of Oklahoma. Together with his first trainee, Dr. Jess Herrmann, Wilkins established the Division of Neurosurgery and its training program in 1946. Through their tireless work, the division and its residency program gained renown for its patient care and teaching, and this tradition was carried forward by its subsequent leaders. The Department of Neurosurgery was established in 1993. From humble beginnings, neurosurgery at the University of Oklahoma has grown a comprehensive residency program with an intensive curriculum, leveraging the clinical and academic breadth afforded by relationships with the College of Medicine, the University of Oklahoma Health Sciences Center, and allied clinical and research partners. Here, the authors recount the history of neurosurgery at the University of Oklahoma, the flagship academic neurosurgical program in the state.


Assuntos
Internato e Residência , Neurocirurgia , Currículo , História do Século XX , Humanos , Neurocirurgia/educação , Procedimentos Neurocirúrgicos , Universidades
3.
J Neurosurg ; 136(2): 565-574, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34359022

RESUMO

The purpose of this report is to chronicle a 2-decade period of educational innovation and improvement, as well as governance reform, across the specialty of neurological surgery. Neurological surgery educational and professional governance systems have evolved substantially over the past 2 decades with the goal of improving training outcomes, patient safety, and the quality of US neurosurgical care. Innovations during this period have included the following: creating a consensus national curriculum; standardizing the length and structure of neurosurgical training; introducing educational outcomes milestones and required case minimums; establishing national skills, safety, and professionalism courses; systematically accrediting subspecialty fellowships; expanding professional development for educators; promoting training in research; and coordinating policy and strategy through the cooperation of national stakeholder organizations. A series of education summits held between 2007 and 2009 restructured some aspects of neurosurgical residency training. Since 2010, ongoing meetings of the One Neurosurgery Summit have provided strategic coordination for specialty definition, neurosurgical education, public policy, and governance. The Summit now includes leadership representatives from the Society of Neurological Surgeons, the American Association of Neurological Surgeons, the Congress of Neurological Surgeons, the American Board of Neurological Surgery, the Review Committee for Neurological Surgery of the Accreditation Council for Graduate Medical Education, the American Academy of Neurological Surgery, and the AANS/CNS Joint Washington Committee. Together, these organizations have increased the effectiveness and efficiency of the specialty of neurosurgery in advancing educational best practices, aligning policymaking, and coordinating strategic planning in order to meet the highest standards of professionalism and promote public health.


Assuntos
Internato e Residência , Neurocirurgia , Educação de Pós-Graduação em Medicina , Bolsas de Estudo , Humanos , Neurocirurgiões/educação , Neurocirurgia/educação , Estados Unidos
5.
J Neurosurg Pediatr ; : 1-9, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34144521

RESUMO

OBJECTIVE: Scoliosis is common in patients with Chiari malformation type I (CM-I)-associated syringomyelia. While it is known that treatment with posterior fossa decompression (PFD) may reduce the progression of scoliosis, it is unknown if decompression with duraplasty is superior to extradural decompression. METHODS: A large multicenter retrospective and prospective registry of 1257 pediatric patients with CM-I (tonsils ≥ 5 mm below the foramen magnum) and syrinx (≥ 3 mm in axial width) was reviewed for patients with scoliosis who underwent PFD with or without duraplasty. RESULTS: In total, 422 patients who underwent PFD had a clinical diagnosis of scoliosis. Of these patients, 346 underwent duraplasty, 51 received extradural decompression alone, and 25 were excluded because no data were available on the type of PFD. The mean clinical follow-up was 2.6 years. Overall, there was no difference in subsequent occurrence of fusion or proportion of patients with curve progression between those with and those without a duraplasty. However, after controlling for age, sex, preoperative curve magnitude, syrinx length, syrinx width, and holocord syrinx, extradural decompression was associated with curve progression > 10°, but not increased occurrence of fusion. Older age at PFD and larger preoperative curve magnitude were independently associated with subsequent occurrence of fusion. Greater syrinx reduction after PFD of either type was associated with decreased occurrence of fusion. CONCLUSIONS: In patients with CM-I, syrinx, and scoliosis undergoing PFD, there was no difference in subsequent occurrence of surgical correction of scoliosis between those receiving a duraplasty and those with an extradural decompression. However, after controlling for preoperative factors including age, syrinx characteristics, and curve magnitude, patients treated with duraplasty were less likely to have curve progression than patients treated with extradural decompression. Further study is needed to evaluate the role of duraplasty in curve stabilization after PFD.

6.
Neurosurgery ; 88(2): 332-341, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33313928

RESUMO

BACKGROUND: Occipital-cervical fusion (OCF) and ventral decompression (VD) may be used in the treatment of pediatric Chiari-1 malformation (CM-1) with syringomyelia (SM) as adjuncts to posterior fossa decompression (PFD) for complex craniovertebral junction pathology. OBJECTIVE: To examine factors influencing the use of OCF and OCF/VD in a multicenter cohort of pediatric CM-1 and SM subjects treated with PFD. METHODS: The Park-Reeves Syringomyelia Research Consortium registry was used to examine 637 subjects with cerebellar tonsillar ectopia ≥ 5 mm, syrinx diameter ≥ 3 mm, and at least 1 yr of follow-up after their index PFD. Comparisons were made between subjects who received PFD alone and those with PFD + OCF or PFD + OCF/VD. RESULTS: All 637 patients underwent PFD, 505 (79.2%) with and 132 (20.8%) without duraplasty. A total of 12 subjects went on to have OCF at some point in their management (PFD + OCF), whereas 4 had OCF and VD (PFD + OCF/VD). Of those with complete data, a history of platybasia (3/10, P = .011), Klippel-Feil (2/10, P = .015), and basilar invagination (3/12, P < .001) were increased within the OCF group, whereas only basilar invagination (1/4, P < .001) was increased in the OCF/VD group. Clivo-axial angle (CXA) was significantly lower for both OCF (128.8 ± 15.3°, P = .008) and OCF/VD (115.0 ± 11.6°, P = .025) groups when compared to PFD-only group (145.3 ± 12.7°). pB-C2 did not differ among groups. CONCLUSION: Although PFD alone is adequate for treating the vast majority of CM-1/SM patients, OCF or OCF/VD may be occasionally utilized. Cranial base and spine pathologies and CXA may provide insight into the need for OCF and/or OCF/VD.


Assuntos
Malformação de Arnold-Chiari/cirurgia , Descompressão Cirúrgica/métodos , Fusão Vertebral/métodos , Siringomielia/cirurgia , Malformação de Arnold-Chiari/complicações , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Siringomielia/complicações , Resultado do Tratamento
7.
Neurosurg Focus ; 25(3): E9, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18759633

RESUMO

Vagus nerve stimulation (VNS) has become an accepted treatment option for pharmacologically resistant epilepsy. Although initially approved for adults, it increasingly has gained acceptance in children. In this article the author reviews the current state of knowledge of VNS therapy and discusses its potential utility.


Assuntos
Terapia por Estimulação Elétrica/métodos , Terapia por Estimulação Elétrica/tendências , Nervo Vago , Fatores Etários , Terapia por Estimulação Elétrica/instrumentação , Eletrodos Implantados , Epilepsias Parciais/fisiopatologia , Epilepsias Parciais/terapia , Humanos , Nervo Vago/fisiologia
8.
J Neurosurg Pediatr ; 22(5): 504-507, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30095345

RESUMO

The authors present a case of Chiari type 1.5 malformation with the uncommon presenting symptoms of esotropia and diplopia due to divergence insufficiency in a 12-year-old girl. Imaging at initial diagnosis revealed cerebellar herniation with extension of the tonsils to the C2 vertebral body, a retroflexed odontoid, and a small cervical syrinx. The patient was initially treated with an uncomplicated Chiari malformation decompression without dural opening. Repeat imaging revealed an adequate decompression. Three months postoperatively the patient's diplopia recurred and she underwent repeat posterior fossa decompression with dural opening and duraplasty. Following repeat decompression with dural opening and duraplasty, the patient's diplopia had not recurred by the 2-year follow-up.https://thejns.org/doi/abs/10.3171/2018.5.PEDS1886.


Assuntos
Malformação de Arnold-Chiari/cirurgia , Fossa Craniana Posterior/cirurgia , Descompressão Cirúrgica/métodos , Dura-Máter/cirurgia , Malformação de Arnold-Chiari/diagnóstico por imagem , Criança , Fossa Craniana Posterior/diagnóstico por imagem , Dura-Máter/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Procedimentos de Cirurgia Plástica/métodos , Resultado do Tratamento
9.
J Neurosurg Pediatr ; 19(5): 571-577, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28291419

RESUMO

OBJECTIVE Experience has led us to suspect an association between shunt malfunction and recent abdominal surgery, yet information about this potential relationship has not been explored in the literature. The authors compared shunt survival in patients who underwent abdominal surgery to shunt survival in our general pediatric shunt population to determine whether such a relationship exists. METHODS The authors performed a retrospective review of all cases in which pediatric patients underwent ventriculoperitoneal shunt operations at their institution during a 7-year period. Survival time in shunt operations that followed abdominal surgery was compared with survival time of shunt operations in patients with no history of abdominal surgery. Univariate and multivariate analyses were used to identify factors associated with failure. RESULTS A total of 141 patients who underwent 468 shunt operations during the period of study were included; 107 of these 141 patients had no history of abdominal surgery and 34 had undergone a shunt operation after abdominal surgery. Shunt surgery performed more than 2 weeks after abdominal surgery was not associated with time to shunt failure (p = 0.86). Shunt surgery performed within 2 weeks after abdominal surgery was associated with time to failure (adjusted HR 3.6, 95% CI 1.3-9.6). CONCLUSIONS Undergoing shunt surgery shortly after abdominal surgery appears to be associated with shorter shunt survival. When possible, some patients may benefit from shunt placement utilizing alternative termini.


Assuntos
Abdome/cirurgia , Análise de Falha de Equipamento , Derivação Ventriculoperitoneal , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Masculino , Análise Multivariada , Reoperação , Estudos Retrospectivos , Risco
10.
J Neurosurg ; 126(2): 586-595, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27035169

RESUMO

OBJECTIVE Aneurysmal subarachnoid hemorrhage (aSAH) may be complicated by hydrocephalus in 6.5%-67% of cases. Some patients with aSAH develop shunt dependency, which is often managed by ventriculoperitoneal shunt placement. The objectives of this study were to review published risk factors for shunt dependency in patients with aSAH, determine the level of evidence for each factor, and calculate the magnitude of each risk factor to better guide patient management. METHODS The authors searched PubMed and MEDLINE databases for Level A and Level B articles published through December 31, 2014, that describe factors affecting shunt dependency after aSAH and performed a systematic review and meta-analysis, stratifying the existing data according to level of evidence. RESULTS On the basis of the results of the meta-analysis, risk factors for shunt dependency included high Fisher grade (OR 7.74, 95% CI 4.47-13.41), acute hydrocephalus (OR 5.67, 95% CI 3.96-8.12), in-hospital complications (OR 4.91, 95% CI 2.79-8.64), presence of intraventricular blood (OR 3.93, 95% CI 2.80-5.52), high Hunt and Hess Scale score (OR 3.25, 95% CI 2.51-4.21), rehemorrhage (OR 2.21, 95% CI 1.24-3.95), posterior circulation location of the aneurysm (OR 1.85, 95% CI 1.35-2.53), and age ≥ 60 years (OR 1.81, 95% CI 1.50-2.19). The only risk factor included in the meta-analysis that did not reach statistical significance was female sex (OR 1.13, 95% CI 0.77-1.65). CONCLUSIONS The authors identified several risk factors for shunt dependency in aSAH patients that help predict which patients are likely to require a permanent shunt. Although some of these risk factors are not independent of each other, this information assists clinicians in identifying at-risk patients and managing their treatment.


Assuntos
Derivações do Líquido Cefalorraquidiano , Hidrocefalia/terapia , Aneurisma Intracraniano/terapia , Hemorragia Subaracnóidea/terapia , Humanos , Hidrocefalia/etiologia , Aneurisma Intracraniano/complicações , Fatores de Risco , Hemorragia Subaracnóidea/complicações
11.
J Neurosurg Spine ; 25(1): 78-87, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26967990

RESUMO

An understanding of the underlying pathophysiology of tethered cord syndrome (TCS) and modern management strategies have only developed within the past few decades. Current understanding of this entity first began with the understanding and management of spina bifida; this later led to the gradual recognition of spina bifida occulta and the symptoms associated with tethering of the filum terminale. In the 17th century, Dutch anatomists provided the first descriptions and initiated surgical management efforts for spina bifida. In the 19th century, the term "spina bifida occulta" was coined and various presentations of spinal dysraphism were appreciated. The association of urinary, cutaneous, and skeletal abnormalities with spinal dysraphism was recognized in the 20th century. Early in the 20th century, some physicians began to suspect that traction on the conus medullaris caused myelodysplasia-related symptoms and that prophylactic surgical management could prevent the occurrence of clinical manifestations. It was not, however, until later in the 20th century that the term "tethered spinal cord" and the modern management of TCS were introduced. This gradual advancement in understanding at a time before the development of modern imaging modalities illustrates how, over the centuries, anatomists, pathologists, neurologists, and surgeons used clinical examination, a high level of suspicion, and interest in the subtle and overt clinical appearances of spinal dysraphism and TCS to advance understanding of pathophysiology, clinical appearance, and treatment of this entity. With the availability of modern imaging, spinal dysraphism can now be diagnosed and treated as early as the intrauterine stage.


Assuntos
Defeitos do Tubo Neural/história , Europa (Continente) , História do Século XVII , História do Século XVIII , História do Século XIX , História do Século XX , História do Século XXI , Humanos , Medicina nas Artes , Defeitos do Tubo Neural/terapia , América do Norte
12.
J Neurosurg Pediatr ; 17(3): 336-42, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26613273

RESUMO

OBJECT The coexistence of Chiari malformation Type I (CM-I) and ventral brainstem compression (VBSC) has been well documented, but the change in VBSC after posterior fossa decompression (PFD) has undergone little investigation. In this study the authors evaluated VBSC in patients with CM-I and determined the change in VBSC after PFD, correlating changes in VBSC with clinical status and the need for further intervention. METHODS Patients who underwent PFD for CM-I by the senior author from November 2005 to January 2013 with complete radiological records were included in the analysis. The following data were obtained: objective measure of VBSC (pB-C2 distance); relationship of odontoid to Chamberlain's, McGregor's, McRae's, and Wackenheim's lines; clival length; foramen magnum diameter; and basal angle. Statistical analyses were performed using paired t-tests and a mixed-effects ANOVA model. RESULTS Thirty-one patients were included in the analysis. The mean age of the cohort was 10.0 years. There was a small but statistically significant increase in pB-C2 postoperatively (0.5 mm, p < 0.0001, mixed-effects ANOVA). Eleven patients had postoperative pB-C2 values greater than 9 mm. The mean distance from the odontoid tip to Wackenheim's line did not change after PFD, signifying postoperative occipitocervical stability. No patients underwent transoral odontoidectomy or occipitocervical fusion. No patients experienced clinical deterioration after PFD. CONCLUSIONS The increase in pB-C2 in patients undergoing PFD may occur as a result of releasing the posterior vector on the ventral dura, allowing it to relax posteriorly. This increase appears to be well-tolerated, and a postoperative pB-C2 measurement of more than 9 mm in light of stable craniocervical metrics and a nonworsened clinical examination does not warrant further intervention.


Assuntos
Malformação de Arnold-Chiari/complicações , Tronco Encefálico/patologia , Fossa Craniana Posterior/cirurgia , Descompressão Cirúrgica/métodos , Compressão da Medula Espinal/cirurgia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Forame Magno/patologia , Humanos , Lactente , Masculino , Processo Odontoide/patologia , Resultado do Tratamento , Adulto Jovem
13.
J Clin Neurosci ; 24: 94-8, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26601815

RESUMO

Ventricular shunt failures and subsequent revisions are a significant source of patient morbidity. We conducted a review of pediatric patients undergoing placement or revision of ventricular shunts at our institution between January 2007 and December 2008. Patients were followed through to July 2014. Data collected included patient demographics, shunt history and indication for procedure, approach taken for shunt placement, and location of shunt tip in relation to the foramen of Monro. Univariate and multivariate analyses were conducted to identify factors associated with proximal failure. A total of 87 procedures were identified in 40 patients, consisting of 23 initial placements and 64 revisions. Thirty-nine proximal catheter malfunctions were identified. Indications for shunt placement included Chiari II malformation (33%) and intraventricular hemorrhage (33%). Mean follow-up period was 5.5 years. Median time to shunt failure was 1.57 years. In the multivariate model, younger age at placement was associated with decreased time to proximal failure (hazard ratio [HR]=0.80 per increasing year of age, 95% confidence interval [CI] 0.64-0.98). Both anterior approach (HR=0.39, 95% CI 0.23-0.67) and farther distance to foramen of Monro (HR=0.02 per increasing 10mm, 95% CI 0.00-0.22) were associated with increased time to proximal failure when the catheter tip was located within the contralateral lateral ventricle. Optimizing outcomes in patients with shunt-dependent hydrocephalus continues to be a challenge. Despite unsatisfactory outcomes, particularly in the pediatric population, few conclusions can be drawn from studies assessing operative variables.


Assuntos
Derivações do Líquido Cefalorraquidiano/efeitos adversos , Hidrocefalia/cirurgia , Complicações Pós-Operatórias/epidemiologia , Adolescente , Derivações do Líquido Cefalorraquidiano/métodos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Reoperação , Estudos Retrospectivos , Fatores de Risco
14.
World Neurosurg ; 86: 514.e13-8, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26344638

RESUMO

BACKGROUND: Chronic subdural hematoma in the pediatric population often results from trauma. Asymptomatic and benign-appearing subdural collections are generally managed conservatively without operative intervention. Primary intracranial sarcomas are uncommon entities. Diagnosis of sarcoma can be difficult because these lesions often manifest as apparent hematoma. CASE DESCRIPTION: Presented is the case of a primary intracranial mucoid spindle cell sarcoma that arose in a child with a history of benign-appearing bilateral subdural fluid collections in the setting of nonaccidental trauma. The patient was initially managed conservatively because her neurological examination result was normal and her subdural collections decreased in size on repeated imaging. The collections did not resolve completely. Years later, she exhibited weakness, seizure, and an increase in the size of her subdural fluid collection. Subdural drainage was attempted without significant effect. Cytologic assessment of fluid was negative for malignant cells. Magnetic resonance imaging revealed multiple enhancing masses along the subdural collection. The patient eventually underwent craniotomy in which a diagnosis of sarcoma was obtained. Pathological and radiographic findings as well as oncological management are reviewed. The authors also review the natural history and treatment of primary intracranial sarcoma in the pediatric population. CONCLUSIONS: Early contrasted magnetic resonance imaging should be obtained in patients with subdural fluid collections that appear asymmetric or do not resolve in the expected time course, despite having a normal neurologic examination result. Negative cytologic assessment does not exclude sarcoma diagnosis.


Assuntos
Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/diagnóstico , Hematoma Subdural Crônico/etiologia , Sarcoma/complicações , Sarcoma/diagnóstico , Neoplasias Encefálicas/cirurgia , Pré-Escolar , Feminino , Hematoma Subdural Crônico/diagnóstico , Hematoma Subdural Crônico/cirurgia , Humanos , Sarcoma/cirurgia
15.
J Clin Neurosci ; 22(11): 1749-52, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26165471

RESUMO

We discuss the association between tethered cord syndrome (TCS) and Chiari type 1 malformation (CM1), and report on the surgical outcomes of children with CM1 and TCS who underwent sectioning of the filum terminale (SFT). The relationship between TCS and CM1 is unclear. A retrospective review of 170 consecutive spinal cord detetherings between 2008 and 2012 was performed. We identified 17 children with CM1 who underwent SFT. Information regarding clinical presentation, radiographic findings, surgical procedures, and clinical outcomes was analyzed. A mean tonsillar herniation of 10.0mm (range: 5-21) was noted. Children with a fatty or thickened filum terminale demonstrated a greater amount of tonsillar displacement (p<0.005). A low conus medullaris was found in 12 children and a syrinx was present in three. The preoperative symptoms improved in all children. The postoperative MRI (mean 21.8 months) revealed an unchanged tonsillar position in all but one child. No worsening of neurologic function was noted. Pediatric patients who have both CM1 and TCS, but do not demonstrate classic Chiari-related symptoms, may experience symptomatic improvement after filum terminale sectioning.


Assuntos
Malformação de Arnold-Chiari/complicações , Malformação de Arnold-Chiari/cirurgia , Defeitos do Tubo Neural/complicações , Defeitos do Tubo Neural/cirurgia , Procedimentos Neurocirúrgicos/métodos , Adolescente , Cauda Equina/cirurgia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Período Pós-Operatório , Estudos Retrospectivos , Resultado do Tratamento
16.
Gene ; 313: 91-101, 2003 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-12957380

RESUMO

Acid sensing ion channel (ASIC)2 belongs to the amiloride-sensitive Na(+)-channel/ degenerin family. Our previous studies suggested that differential regulation of ASIC2 expression occurs between high-grade glial-derived tumor cells and normal astrocytes. To investigate the mechanisms involved in the regulation of ASIC2 gene expression, the human ASIC2 promoter region (-1551 to +117) was cloned and characterized. The ASIC2 promoter lacked a canonical TATA box, but contained one putative CCAAT box. Nucleotide sequencing of the promoter revealed the presence of a number of transcription factor-binding sites and a 404 bp CpG island upstream the transcription start site. Nested deletion mutants and transfection results showed that the construct between -133 and +117 base pairs conferred basal transcription specific activity. Mutation of Sp1 and CP2 sites in this region resulted in a 70 and 95% decrease in promoter activity, respectively. Gel shift assays demonstrated the existence of specific protein binding to the SP1 and CP2 elements. There was no mutation in the CpG island in six glioma cell lines, but methylation-specific PCR showed methylation in some of glioma cell lines and tumor tissues, and treatment with the methylation inhibitor 5-Aza-2'-deoxycytidine could partially restore ASIC2 expression in cell lines, suggesting that epigenetic mechanisms may contribute to dysregulated ASIC2 expression.


Assuntos
Azacitidina/análogos & derivados , Proteínas de Membrana , Proteínas do Tecido Nervoso , Regiões Promotoras Genéticas/genética , Canais de Sódio/genética , Canais Iônicos Sensíveis a Ácido , Azacitidina/farmacologia , Sequência de Bases , Sítios de Ligação/genética , Encéfalo/metabolismo , Clonagem Molecular , Ilhas de CpG/genética , DNA/química , DNA/genética , Metilação de DNA , Proteínas de Ligação a DNA/metabolismo , Decitabina , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioma/genética , Glioma/patologia , Glioma/fisiopatologia , Humanos , Luciferases/genética , Luciferases/metabolismo , Potenciais da Membrana/efeitos dos fármacos , Dados de Sequência Molecular , Mutação , Técnicas de Patch-Clamp , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Análise de Sequência de DNA , Canais de Sódio/fisiologia , Fator de Transcrição Sp1/metabolismo , Fatores de Transcrição/metabolismo , Sítio de Iniciação de Transcrição , Transfecção , Células Tumorais Cultivadas/efeitos dos fármacos
18.
J Neurosurg Pediatr ; 10(2): 142-9, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22747093

RESUMO

OBJECT: The authors debate the optimal management for Chiari malformation Type I (CM-I) while sharing their experience with posterior fossa decompression and duraplasty (PFDD). METHODS: The charts of 48 consecutive pediatric patients surgically treated for CM-I were retrospectively reviewed. RESULTS: Patients ranged in age from 2 to 17 years with an average age of 9.8 years. The most common presentations were headache, affecting 34 patients (71%), and pain (neck, back, or extremities), affecting 21 patients (44%). Twenty-seven patients (56%) had a syrinx. All 48 patients underwent PFDD utilizing acellular tissue matrix. The average hospital stay overall was 3.56 days, whereas the average stay for patients with (29 [60%] of 48) or without (19 [40%] of 48) scoliosis and/or syringomyelia was 3.72 and 3.32 days, respectively. The odds of a patient having a hospital stay of 4 or more days was nearly 3 times greater in patients with scoliosis and/or syringomyelia as compared with patients without either condition (OR 2.73, 95% CI 0.74-10.11, p = 0.1330). The average hospital stay for patients 0-8 years of age was 3.29 days; and for those 9-17 years of age, 3.78 days. The odds of a patient having a hospital stay of 4 or more days was nearly 4 times greater in 9- to 17-year-olds as compared with 0- to 8-year-olds (OR 3.73, 95% CI 1.03-13.52, p = 0.0455). Forty patients (89%) experienced early improvement in their signs and symptoms following PFDD. There were 2 revision PFDDs (4%). CONCLUSIONS: Posterior fossa decompression and duraplasty is a safe and effective surgical option in the management of pediatric CM-I.


Assuntos
Malformação de Arnold-Chiari/cirurgia , Dura-Máter/cirurgia , Adolescente , Materiais Biocompatíveis , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do Tratamento
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