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1.
Hum Mol Genet ; 22(20): 4053-63, 2013 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-23727838

RESUMO

Human cortical malformations, including lissencephaly, polymicrogyria and other diseases of neurodevelopment, have been associated with mutations in microtubule subunits and microtubule-associated proteins. Here we report our cloning of the brain dimple (brdp) mouse mutation, which we recovered from an ENU screen for recessive perinatal phenotypes affecting neurodevelopment. We identify the causal mutation in the tubulin, beta-2b (Tubb2b) gene as a missense mutation at a highly conserved residue (N247S). Brdp/brdp homozygous mutants have significant thinning of the cortical epithelium, which is markedly more severe in the caudo-lateral portion of the telencephalon, and do not survive past birth. The cortical defects are largely due to a major increase in apoptosis and we note abnormal proliferation of the basal progenitors. Adult brdp/+ mice are viable and fertile but exhibit behavioral phenotypes. This allele of Tubb2b represents the most severely affected mouse tubulin phenotype reported to date and this is the first report of a tubulin mutation affecting neuronal proliferation and survival.


Assuntos
Córtex Cerebral/anormalidades , Genes Letais , Malformações do Desenvolvimento Cortical/genética , Malformações do Desenvolvimento Cortical/patologia , Mutação de Sentido Incorreto , Tubulina (Proteína)/genética , Animais , Encéfalo/anormalidades , Encéfalo/embriologia , Encéfalo/metabolismo , Proliferação de Células , Sobrevivência Celular , Córtex Cerebral/embriologia , Córtex Cerebral/metabolismo , Clonagem Molecular , Evolução Molecular , Feminino , Humanos , Masculino , Camundongos , Modelos Moleculares , Dados de Sequência Molecular , Células NIH 3T3 , Neurônios/fisiologia , Fenótipo , Conformação Proteica , Alinhamento de Sequência , Tubulina (Proteína)/química
2.
Neuromodulation ; 17(7): 670-6; discussion 676-7, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24512097

RESUMO

OBJECTIVES: Percutaneous spinal cord stimulation electrodes have a propensity to migrate longitudinally, which is a costly complication that often compromises therapeutic effect. After implementing simple changes to our percutaneous electrode anchoring technique, we no longer encounter this migration. The current retrospective study updates previously reported results. MATERIALS AND METHODS: We retrospectively examined data in a consecutive series of patients in whom we had secured a new percutaneous electrode by injecting < 0.1 cm(3) of adhesive into the silicone elastomer lead anchor. From 1998 through 2006, we used whichever anchor was supplied with each lead until we observed one case of migration through a short anchor; thereafter, we used a long, tapered anchor exclusively. From 2007 through 2013, we further modified our technique by adding a fascial incision to accommodate the tip of the anchor and by increasing the strength of our suture material. RESULTS: In the first series of 291 patients, followed through July 2007 (mean 4.75 years, range 1.1-9.0 years), 4 (1.37%) experienced electrode migration requiring surgical revision. Only one lead had moved with respect to its anchor; the other three anchors remained securely bonded to their leads. No migration (0.00%) occurred in the second series of 142 patients, followed through 2013 (mean follow-up 2.86 years, range 0.10-5.45 years). CONCLUSION: Improvements to our simple, inexpensive technique apparently have eliminated the most common complication of spinal cord stimulation.


Assuntos
Eletrodos Implantados/efeitos adversos , Migração de Corpo Estranho/etiologia , Migração de Corpo Estranho/prevenção & controle , Pele/inervação , Estimulação da Medula Espinal/efeitos adversos , Idoso , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
4.
J Viral Hepat ; 18(5): 349-57, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-20529202

RESUMO

The hepatitis C virus (HCV) RNA polymerase (RdRp) may be a target of the drug ribavirin, and it is an object of drug development. Independent isolates of any HCV subtype differ genetically by approximately 10%, but the effects of this variation on enzymatic activity and drug sensitivity are poorly understood. We proposed that nucleotide use profiles (G/U ratio) among subtype 1b RdRps may reflect their use of ribavirin. Here, we characterized how subtype 1b genetic variation affects RNA polymerase activity and evaluated the G/U ratio as a surrogate for ribavirin use during pegylated interferon α and ribavirin therapy. Genetic and biochemical variation in the RdRp was compared between responders who would be largely sensitive to ribavirin and relapsers who would be mostly resistant. There were no consistent genetic differences between responder and relapser RdRps. RNA polymerization, RNA binding and primer usage varied widely among the RdRps, but these parameters did not differ significantly between the response groups. The G/U ratio among a set of subtype 1a RdRps increased rather than decreased following failed therapy, as would be expected if it reflected ribavirin use. Finally, RdRp activity was significantly associated with ALT levels. These data indicate that (i) current genetic approaches cannot predict RNA polymerase behaviour, (ii) the G/U ratio is not a surrogate for ribavirin use, (iii) RdRp activity may contribute to liver disease by modulating viral mRNA and antigen levels, and (iv) drug candidates should be tested against multiple patient-derived enzymes to ensure widespread efficacy even within a viral subtype.


Assuntos
Antivirais/uso terapêutico , RNA Polimerases Dirigidas por DNA/efeitos dos fármacos , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Proteínas não Estruturais Virais/metabolismo , Antivirais/administração & dosagem , Antivirais/farmacologia , RNA Polimerases Dirigidas por DNA/genética , RNA Polimerases Dirigidas por DNA/metabolismo , Quimioterapia Combinada , Variação Genética/genética , Hepacivirus/enzimologia , Hepacivirus/genética , Hepatite C/virologia , Humanos , Interferon-alfa/administração & dosagem , Interferon-alfa/farmacologia , Interferon-alfa/uso terapêutico , RNA Viral/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Recidiva , Ribavirina/administração & dosagem , Ribavirina/farmacologia , Ribavirina/uso terapêutico , Proteínas não Estruturais Virais/genética
5.
Med Teach ; 32(8): 676-82, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20662580

RESUMO

Competency-based medical education (CBME), by definition, necessitates a robust and multifaceted assessment system. Assessment and the judgments or evaluations that arise from it are important at the level of the trainee, the program, and the public. When designing an assessment system for CBME, medical education leaders must attend to the context of the multiple settings where clinical training occurs. CBME further requires assessment processes that are more continuous and frequent, criterion-based, developmental, work-based where possible, use assessment methods and tools that meet minimum requirements for quality, use both quantitative and qualitative measures and methods, and involve the wisdom of group process in making judgments about trainee progress. Like all changes in medical education, CBME is a work in progress. Given the importance of assessment and evaluation for CBME, the medical education community will need more collaborative research to address several major challenges in assessment, including "best practices" in the context of systems and institutional culture and how to best to train faculty to be better evaluators. Finally, we must remember that expertise, not competence, is the ultimate goal. CBME does not end with graduation from a training program, but should represent a career that includes ongoing assessment.


Assuntos
Educação Baseada em Competências/organização & administração , Educação de Graduação em Medicina , Avaliação de Desempenho Profissional/organização & administração , Competência Clínica/normas , Humanos
6.
Med Teach ; 32(8): 638-45, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20662574

RESUMO

Although competency-based medical education (CBME) has attracted renewed interest in recent years among educators and policy-makers in the health care professions, there is little agreement on many aspects of this paradigm. We convened a unique partnership - the International CBME Collaborators - to examine conceptual issues and current debates in CBME. We engaged in a multi-stage group process and held a consensus conference with the aim of reviewing the scholarly literature of competency-based medical education, identifying controversies in need of clarification, proposing definitions and concepts that could be useful to educators across many jurisdictions, and exploring future directions for this approach to preparing health professionals. In this paper, we describe the evolution of CBME from the outcomes movement in the 20th century to a renewed approach that, focused on accountability and curricular outcomes and organized around competencies, promotes greater learner-centredness and de-emphasizes time-based curricular design. In this paradigm, competence and related terms are redefined to emphasize their multi-dimensional, dynamic, developmental, and contextual nature. CBME therefore has significant implications for the planning of medical curricula and will have an important impact in reshaping the enterprise of medical education. We elaborate on this emerging CBME approach and its related concepts, and invite medical educators everywhere to enter into further dialogue about the promise and the potential perils of competency-based medical curricula for the 21st century.


Assuntos
Educação Baseada em Competências/história , Educação de Graduação em Medicina , Modelos Teóricos , Educação Baseada em Competências/organização & administração , História do Século XX , Humanos
7.
J Viral Hepat ; 16(8): 595-604, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19243495

RESUMO

Hepatitis C virus (HCV) infections are treated with interferon alpha plus ribavirin, but it is unknown how ribavirin works against HCV. Ribavirin is a guanosine analogue that can be a substrate for the viral RNA polymerase. HCV is genetically variable, and this genetic variation could affect the polymerase's use of ribavirin triphosphate. Thirteen patients infected with HCV who failed interferon alpha monotherapy and were retreated with interferon alpha plus ribavirin were identified; seven were responders and six were nonresponders to combination therapy. The consensus sequences encoding the 13 polymerases plus seven sequences from treatment-naive controls were determined. The responder sequences were more genetically variable than the nonresponders and controls, the amino acid variations unique to responders had lower BLOSUM90 scores than variations in nonresponders and controls, and the amino acid variations correlated with response to therapy clustered around the RNA-binding channel of the polymerase. These data imply that that the responder enzymes were probably more functionally variable than the nonresponder enzymes. Enzymatic activity was measured for 10 recombinant polymerases; RNA synthesis activity varied by over sevenfold and polymerases from two of the responders used GTP much better than UTP, but technical limitations prevented direct measurement of ribavirin triphosphate use. Because response to combination therapy in these patients was primarily due to addition of ribavirin to the treatment regimen, these data imply that genetic variation in the polymerase may have affected the efficiency of ribavirin incorporation into the viral genome and hence may have modulated ribavirin's efficacy against HCV.


Assuntos
Antivirais/farmacologia , RNA Polimerases Dirigidas por DNA/metabolismo , Hepacivirus/efeitos dos fármacos , Ribavirina/farmacologia , Proteínas Virais/metabolismo , Sequência de Aminoácidos , RNA Polimerases Dirigidas por DNA/genética , Variação Genética , Hepatite C Crônica/tratamento farmacológico , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Mutação de Sentido Incorreto , Estrutura Terciária de Proteína , RNA Viral/biossíntese , Ribavirina/uso terapêutico , Alinhamento de Sequência , Análise de Sequência de DNA , Proteínas Virais/genética
8.
J Neurosurg Spine ; 8(4): 327-34, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18377317

RESUMO

OBJECT: Laminar fixation of the axis with crossing bilateral screws has been shown to provide rigid fixation with a theoretically decreased risk of vertebral artery damage compared with C1-2 transarticular screw fixation and C-2 pedicle screw fixation. Some studies, however, have shown restricted rigidity of such screws compared with C-2 pedicle screws, and others note that anatomical variability exists within the posterior elements of the axis that may have an impact on successful placement. To elucidate the clinical impact of such screws, the authors report their experience in placing C-2 laminar screws in adult patients over a 2-year period, with emphasis on clinical outcome and technical placement. METHODS: Sixteen adult patients with cervical instability underwent posterior cervical and cervicothoracic fusion procedures at our institution with constructs involving C-2 laminar screws. Eleven patients were men and 5 were women, and they ranged in age from 28 to 84 years (mean 57 years). The reasons for fusion were degenerative disease (9 patients) and treatment of trauma (7 patients). In 14 patients (87.5%) standard translaminar screws were placed, and in 2 (12.5%) an ipsilateral trajectory was used. All patients underwent preoperative radiological evaluation of the cervical spine, including computed tomography scanning with multiplanar reconstruction to assess the posterior anatomy of C-2. Anatomical restrictions for placement of standard translaminar screws included a deeply furrowed spinous process and/or an underdeveloped midline posterior ring of the axis. In these cases, screws were placed into the corresponding lamina from the ipsilateral side, allowing bilateral screws to be oriented in a more parallel, as opposed to perpendicular, plane. All patients were followed for >2 years to record rates of fusion, instrumentation failure, and other complications. RESULTS: Thirty-two screws were placed without neurological or vascular complications. The mean follow-up duration was 27.3 months. Complications included 2 revisions, one for pseudarthrosis and the other for screw pullout, and 3 postoperative infections. CONCLUSIONS: Placement of laminar screws into the axis from the standard crossing approach or via an ipsilateral trajectory may allow a safe, effective, and durable means of including the axis in posterior cervical and cervicothoracic fusion procedures.


Assuntos
Vértebra Cervical Áxis , Parafusos Ósseos , Doenças da Coluna Vertebral/cirurgia , Fusão Vertebral/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Laminectomia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Doenças da Coluna Vertebral/diagnóstico , Doenças da Coluna Vertebral/etiologia , Fusão Vertebral/instrumentação , Fatores de Tempo , Resultado do Tratamento
9.
Toxicology ; 409: 24-32, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30055299

RESUMO

Welding fumes were reclassified as a Group 1 carcinogen by the International Agency for Research on Cancer in 2017. Gas metal arc welding (GMAW) is a process widely used in industry. Fume generated from GMAW-mild steel (MS) is abundant in iron with some manganese, while GMAW-stainless steel (SS) fume also contains significant amounts of chromium and nickel, known carcinogenic metals. It has been shown that exposure to GMAW-SS fume in A/J mice promotes lung tumors. The objective was to determine if GMAW-MS fume, which lacks known carcinogenic metals, also promotes lung tumors in mice. Male A/J mice received a single intraperitoneal injection of corn oil or the initiator 3-methylcholanthrene (MCA; 10 µg/g) and, one week later, were exposed by whole-body inhalation to GMAW-MS aerosols for 4 hours/day x 4 days/week x 8 weeks at a mean concentration of 34.5 mg/m3. Lung nodules were enumerated by gross examination at 30 weeks post-initiation. GMAW-MS fume significantly increased lung tumor multiplicity in mice initiated with MCA (21.86 ± 1.50) compared to MCA/air-exposed mice (8.34 ± 0.59). Histopathological analysis confirmed these findings and also revealed an absence of inflammation. Bronchoalveolar lavage analysis also indicated a lack of lung inflammation and toxicity after short-term inhalation exposure to GMAW-MS fume. In conclusion, this study demonstrates that inhalation of GMAW-MS fume promotes lung tumors in vivo and aligns with epidemiologic evidence that shows MS welders, despite less exposure to carcinogenic metals, are at an increased risk for lung cancer.


Assuntos
Poluentes Ocupacionais do Ar/toxicidade , Carcinógenos/toxicidade , Ferro/toxicidade , Neoplasias Pulmonares/induzido quimicamente , Aço , Soldagem , Administração por Inalação , Animais , Neoplasias Pulmonares/patologia , Masculino , Camundongos
10.
J Neurosurg ; 107(2): 347-51, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17695389

RESUMO

OBJECT: Cerebrospinal fluid (CSF) rhinorrhea remains a significant cause of morbidity after resection of vestibular schwannomas (VSs), with rates of rhinorrhea after this procedure reported to range between 0 and 27%. The authors investigated whether reconstruction of the drilled posterior wall of the porus acusticus with hydroxyapatite cement (HAC) would decrease the incidence of postoperative CSF rhinorrhea. METHODS: A prospective observational study of 130 consecutive patients who underwent surgery for reconstruction of the posterior wall of the drilled porus acusticus with HAC was conducted between October 2002 and September 2005. All patients underwent a retrosigmoid transmeatal approach for VS resection and were followed up to document cases of CSF rhinorrhea, incisional CSF leak, meningitis, or rhinorrhea-associated meningitis. A cohort of 150 patients with VSs who were treated with the same surgical approach but without HAC reconstruction served as a control group. RESULTS: The authors found that HAC reconstruction of the porus acusticus wall significantly reduced the rate of postoperative CSF rhinorrhea in their patients. In the patients treated with HAC, rhinorrhea developed in only three patients (2.3%) compared with 18 patients (12%) in the control group. This was a statistically significant finding (p = 0.002, odds ratio = 5.8). CONCLUSIONS: The use of HAC in the reconstruction of the drilled posterior wall of the porus acusticus, occluding exposed air cells, greatly reduces the risk of CSF rhinorrhea.


Assuntos
Rinorreia de Líquido Cefalorraquidiano/etiologia , Rinorreia de Líquido Cefalorraquidiano/prevenção & controle , Hidroxiapatitas/uso terapêutico , Neuroma Acústico/cirurgia , Osso Petroso/cirurgia , Complicações Pós-Operatórias , Adulto , Seguimentos , Humanos , Pessoa de Meia-Idade , Neuroma Acústico/patologia , Estudos Prospectivos , Resultado do Tratamento
11.
J Neurosurg ; 106(2): 210-6, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17410701

RESUMO

OBJECT: Opioid administration after major intracranial surgery is often limited by a presumed lack of need and a concern that opioids will adversely affect the postoperative neurological examination. The authors conducted a prospective study to evaluate the incidence, severity, and treatment of postoperative pain in patients who underwent major intracranial surgery. METHODS: One hundred eighty-seven patients (77 men and 110 women, mean age 52 +/- 15 years, mean weight 78.1 +/- 19.9 kg) underwent either supratentorial (129 patients) or infratentorial (58 patients) procedures. Sixty-nine percent of the patients reported experiencing moderate to severe pain (> or =4 on a 0-10 scale) during the 1st postoperative day. Pain scores greater than or equal to 4 persisted in 48% on the 2nd postoperative day. Approximately 80% of patients were treated with acetaminophen on the 1st postoperative day, whereas opioids (primarily intravenous fentanyl) were administered to 58%. Compared with patients who underwent supratentorial procedures, those who underwent infratentorial procedures reported more severe pain at rest (mean score 4.9 +/- 2.2 compared with 3.8 +/- 2.6; p = 0.015) and with movement (mean score 6.3 +/- 2.6 compared with 4.5 +/- 2.7; p < 0.001) on the 1st postoperative day. On both the 1st and 2nd postoperative days, patients who underwent infratentorial procedures received greater quantities of opioid (p < or = 0.019) and nonopioid (p < or = 0.013) analgesics than those who underwent supratentorial procedures. Patients' dissatisfaction with analgesic therapy was significantly associated with elevated pain levels on the first 2 postoperative days (p < 0.001). CONCLUSIONS: In contrast to prevailing assumptions, the study findings reveal that most patients undergoing elective major intracranial surgery will experience moderate to severe pain for the first 2 days after surgery and that this pain is often inadequately treated.


Assuntos
Analgésicos/uso terapêutico , Craniotomia/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/epidemiologia , Adulto , Idoso , Analgésicos/efeitos adversos , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Bloqueio Nervoso , Medição da Dor , Satisfação do Paciente , Estudos Prospectivos , Resultado do Tratamento
12.
Surg Neurol ; 68(4): 443-8; discussion 448, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17905071

RESUMO

BACKGROUND: Anterior sacral meningocele is a rare congenital malformation, whose open surgical treatment is well accepted. We present a laparoscopic approach as an adjunctive approach. METHODS: Five women who underwent laparoscopic transperitoneal surgery were clinically, radiologically, and surgically evaluated. RESULT: All 5 patients underwent laparoscopic transperitoneal surgery and showed satisfactory results. They had no major complications. Three patients had headaches as minor complications, but it was gone in at most 3 days. Decrease in operative time, blood loss, and length of hospitalization were the advantages of the procedure. CONCLUSIONS: The laparoscopic approach to treating anterior sacral meningocele was feasible and safe, with only minor complications.


Assuntos
Laparoscopia/métodos , Meningocele/cirurgia , Procedimentos Neurocirúrgicos/métodos , Adulto , Anestesia Geral , Perda Sanguínea Cirúrgica , Feminino , Cefaleia/epidemiologia , Cefaleia/etiologia , Humanos , Laparoscopia/efeitos adversos , Imageamento por Ressonância Magnética , Síndrome de Marfan/complicações , Meninges/anatomia & histologia , Meninges/cirurgia , Meningocele/diagnóstico por imagem , Procedimentos Neurocirúrgicos/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Tomografia Computadorizada por Raios X
13.
Spine J ; 7(1): 118-32, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17197345

RESUMO

BACKGROUND CONTENT: There are currently a number of generic and disease-specific instruments for assessing complaints of low back pain (LBP). None provide the comprehensive coverage of the wide range of factors that are considered essential in evaluating treatment outcomes. PURPOSE: To develop and evaluate the psychometric properties of a comprehensive, disease-specific questionnaire for characterizing complaints of LBP and evaluating the outcomes of treatments for these complaints. STUDY DESIGN: A clinical-cohort study of a large, convenience sample of LBP patients. METHODS: We have developed a comprehensive, disease-specific questionnaire for characterizing complaints of LBP and evaluating the outcomes of treatments for these complaints. A large group of patients who sought treatment for LBP (n=2539) completed the Lumbar Spine Outcomes Questionnaire (LSOQ) before treatment, and at 12 and 24 months after treatment. For each subject and for each evaluation period, scores on six composite measures were derived from the subjects' responses to the questionnaire: a LBP severity score, a leg pain severity score, a functional disability score, a psychological distress score, a physical symptoms score, and a health-care utilization score. These scores were used to evaluate the reliability, validity, and responsiveness of the questionnaire. RESULTS: Test-retest reliability of the LSOQ was evaluated by correlating the subject's 12-month scores on each composite measure with the corresponding 24-month scores. Intraclass coefficients of correlation were used. The obtained coefficients of correlation [(a) LBP severity, 0.87; (b) leg pain severity, 0.85; (c) functional disability, 0.87; (d) psychological distress, 0.88; (e) physical symptoms other than pain, 0.82; and (f) health-care utilization, 0.76] indicate good test-retest reliability for the LSOQ. Construct validity was evaluated by correlating scores on the composite measures derived from the LSOQ with scores on measures of the same constructs derived from the Oswestry Low Back Pain Disability Questionnaire and the Short Form 36-Item Health Survey. The coefficients of correlation were relatively high (mostly between .7 and .9), indicating good construct validity. Construct validity was also evaluated by comparing the scores of groups of subjects who were known to differ or not to differ on the composite measures, using multivariate analyses of variance. Significant multivariate and univariate differences were obtained between groups who were expected to differ (ie, surgically and nonsurgically treated patients). No significant differences were found for groups who were not expected to differ (ie, patients with similar diagnosis, but different surgical treatments). Responsiveness was assessed by evaluating differences in the 24-month change scores between improved and unimproved subjects. Large and significant differences were obtained between improved and unimproved subjects for all composite measures derived from the LSOQ. The observed effect sizes ranged from .68 to 1.17 indicating that the LSOQ is highly responsive. CONCLUSION: The LSOQ appears to be acceptable to patients, easy to administer, highly reliable, valid, and responsive. It provides information on demographics, pain severity, functional disability, psychological distress, physical symptoms, health-care utilization, and satisfaction. It should be considered for use in both clinical and research applications as well as regulatory review involving patients with LBP complaints.


Assuntos
Dor Lombar/terapia , Avaliação de Resultados em Cuidados de Saúde , Psicometria/instrumentação , Inquéritos e Questionários , Estudos de Coortes , Avaliação da Deficiência , Feminino , Humanos , Dor Lombar/fisiopatologia , Dor Lombar/psicologia , Masculino , Medição da Dor/métodos , Psicometria/métodos , Reprodutibilidade dos Testes
14.
J Neurosurg Spine ; 24(5): 700-7, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26745352

RESUMO

OBJECTIVE Tarlov cysts (TCs) occur most commonly on extradural components of the sacral and coccygeal nerve roots. These lesions are often found incidentally, with an estimated prevalence of 4%-9%. Given the low estimated rates of symptomatic TC and the fact that symptoms can overlap with other common causes of low-back pain, optimal management of this entity is a matter of ongoing debate. Here, the authors investigate the effects of surgical intervention on symptomatic TCs and aim to solidify the surgical criteria for this disease process. METHODS The authors performed a retrospective review of data from consecutive patients who were surgically treated for symptomatic TCs from September 2011 to March 2013. Clinical evaluations and results from surveying pain and overall health were used. Univariate statistical analyses were performed. RESULTS Twenty-three adults (4 males, 19 females) who had been symptomatic for a mean of 47.4 months were treated with laminectomy, microsurgical exposure and/or imbrication, and paraspinous muscle flap closure. Eighteen patients (78.3%) had undergone prior interventions without sustained improvement. Thirteen patients (56.5%) underwent lumbar drainage for an average of 8.7 days following surgery. The mean follow-up was 14.4 months. Univariate analyses demonstrated that an advanced age (p = 0.045), the number of noted perineural cysts on preoperative imaging (p = 0.02), and the duration of preoperative symptoms (p = 0.03) were associated with a poor postoperative outcome. Although 47.8% of the patients were able to return to normal activities, 93.8% of those surveyed reported that they would undergo the operation again if given the choice. CONCLUSIONS This is one of the largest published studies on patients with TCs treated microsurgically. The data suggest that patients with symptomatic TCs may benefit from open microsurgical treatment. Although outcomes seem related to patient age, duration of symptoms, and extent of disease demonstrated on imaging, further study is warranted and underway.


Assuntos
Laminectomia/métodos , Dor Lombar/cirurgia , Microcirurgia/métodos , Músculos Paraespinais/cirurgia , Cistos de Tarlov/cirurgia , Adulto , Feminino , Humanos , Dor Lombar/diagnóstico por imagem , Região Lombossacral/diagnóstico por imagem , Região Lombossacral/cirurgia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Músculos Paraespinais/diagnóstico por imagem , Estudos Retrospectivos , Cistos de Tarlov/diagnóstico por imagem , Resultado do Tratamento
15.
Genetics ; 151(1): 331-41, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9872971

RESUMO

The regulatory transposon of the Mutator system of transposable elements in maize is MuDR. MuDR elements produce two transcripts, from genes mudrA and mudrB, encoding proteins MURA and MURB, respectively. Like many other transposons, MuDR elements often undergo deletions, usually of internal sequences. Analysis of a deletion that is restricted to the region encoding MURB demonstrates that this gene is not required to cause excisions of a reporter element, although it may be required for transposition or suppression of suppressible alleles. Conversely, a derivative that lacks the region encoding MURA but that produces MURB is nonfunctional for all aspects of Mutator activity. Northern analysis of these derivatives reveals that each of the two transcripts can be independently transcribed, and analysis using an antibody specific for MURB reveals that mudrB transcript can also be successfully translated and its product appropriately localized in the absence of mudrA. A third deletion derivative provides evidence for a source of previously reported antisense transcript.


Assuntos
Elementos de DNA Transponíveis , Proteínas de Plantas/genética , Zea mays/genética , Alelos , Metilação de DNA , Genes de Plantas , Mutagênese , RNA Antissenso
16.
Laryngoscope ; 115(1): 93-8, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15630374

RESUMO

OBJECTIVES: As stereotactic radiation has emerged as a treatment option for acoustic neuromas, cases that require surgical salvage after unsuccessful radiation have emerged. We present a comparison of the technical challenges faced by the surgeons in the treatment of irradiated versus nonirradiated acoustic neuromas. STUDY DESIGN: Matched case-control series. METHODS: We identified nine patients with acoustic neuromas that required surgical resection after radiation therapy. Cases were performed with suboccipital and translabyrinthine approaches. Nine nonirradiated case-control subjects matched for age, sex, tumor size, and surgical approach were identified for purposes of general comparison. Operative findings and outcomes were compared for the two groups. RESULTS: Surgical removal was found to be significantly more difficult after radiation therapy because of increased fibrosis and adhesion to adjacent nervous structures, particularly at the porus acousticus. Excessive scarring hindered identification of the facial nerve and added uncertainty as to the completeness of tumor removal. Decompression of the internal auditory canal (IAC) dura and resection of neoplasm in the IAC before cerebellopontine angle dissection was required for facial nerve identification. Operative time was significantly longer for irradiated cases, and facial nerve outcomes tended to be poorer, particularly when facial nerve dysfunction prompted the salvage procedure. CONCLUSIONS: Surgical salvage of acoustic neuromas after radiation therapy is feasible, but it presents technical challenges beyond that associated with primary surgical therapy. Poorer outcomes of postoperative cranial nerve status were caused primarily by anatomic changes at the nerve/tumor interface. As surgical experience with the irradiated acoustic neuroma grows, operative observations should be incorporated into the counsel provided to patients with acoustic neuromas as they weigh different management options.


Assuntos
Neuroma Acústico/cirurgia , Adulto , Idoso , Estudos de Casos e Controles , Humanos , Pessoa de Meia-Idade , Neuroma Acústico/patologia , Neuroma Acústico/radioterapia , Procedimentos Cirúrgicos Otorrinolaringológicos/métodos , Radiocirurgia , Terapia de Salvação , Falha de Tratamento
17.
Pain ; 87(1): 89-97, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10863049

RESUMO

We have developed a simple procedure for assigning persistent low back pain patients to one of four mutually exclusive, hierarchically organized classes. The procedure relies on the spatial distribution of a patient's pain and the results of straight leg raise tests to make the assignment. We have applied the procedure to a large group of patients who sought treatment for persistent LBP at several university affiliated tertiary care clinics, and found that the resulting four classes of patients were significantly different from one another in their presentation, and in the way they were evaluated and treated by physicians. We concluded that the procedure may have practical research and clinical applications.


Assuntos
Dor Lombar/diagnóstico , Ciática/diagnóstico , Estresse Psicológico/diagnóstico , Adulto , Idoso , Recursos em Saúde/estatística & dados numéricos , Humanos , Dor Lombar/complicações , Dor Lombar/psicologia , Pessoa de Meia-Idade , Medição da Dor , Inventário de Personalidade , Ciática/complicações , Ciática/psicologia , Índice de Gravidade de Doença , Estresse Psicológico/complicações , Estados Unidos
18.
Pain ; 17(2): 189-195, 1983 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-6606154

RESUMO

We wished to determine if pain relief that resulted from transcutaneous (TNS) or spinal cord electrical stimulation in patients with chronic pain was due to activation of an endogenous opiate-related pain control system. Naloxone (0.4-10 mg) or saline was injected in double-blind fashion intravenously into opiate-naive subjects with chronic pain who achieved 30% or greater pain relief with spinal cord stimulation (4 patients) or TNS (9 patients). Subjects rated their pain during stimulation and 2, 5, 10 and 15 min after the injection. Two days or more later the procedure was repeated using the alternate agent (naloxone or saline). Naloxone did not decrease the pain relief induced by stimulation, and therefore the effects of stimulation are probably not mediated by the endogenous opiates.


Assuntos
Terapia por Estimulação Elétrica , Naloxona/farmacologia , Manejo da Dor , Doença Crônica , Método Duplo-Cego , Terapia por Estimulação Elétrica/métodos , Endorfinas/fisiologia , Espaço Epidural , Humanos , Estudos Prospectivos , Medula Espinal , Estimulação Elétrica Nervosa Transcutânea
19.
Neurosurgery ; 52(5): 1056-63; discussion 1063-5, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12699547

RESUMO

OBJECTIVE: Improved clinical and economic outcomes for high-risk surgical procedures have been previously cited in support of regionalization. The goal of this study was to examine the effects of regionalization by analyzing the cost and outcome of craniotomy for tumors and to compare the findings in academic medical centers versus community-based hospitals. METHODS: Outcomes and charges were analyzed for all adult patients undergoing craniotomy for tumor in 33 nonfederal acute care hospitals in Maryland using the Maryland Health Service Cost Review Commission database for the years 1990 to 1996. A total of 4723 patients who underwent craniotomy for tumor were selected on the basis of Diagnostic Related Group 1 (craniotomy except for trauma, age 18 or older) and International Classification of Diseases-9th Revision diagnosis code for benign tumor, primary malignant neoplasm, or secondary malignant neoplasm (codes 191, 192, 194, 200, 225, 227, 228, 237, and 239). Hospitals were categorized as high-volume hospitals (>50 craniotomies/yr) or low-volume hospitals (

Assuntos
Centros Médicos Acadêmicos/economia , Centros Médicos Acadêmicos/estatística & dados numéricos , Neoplasias Encefálicas/economia , Neoplasias Encefálicas/cirurgia , Craniotomia/economia , Craniotomia/estatística & dados numéricos , Preços Hospitalares/estatística & dados numéricos , Avaliação de Resultados em Cuidados de Saúde/economia , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Encaminhamento e Consulta/economia , Encaminhamento e Consulta/estatística & dados numéricos , Programas Médicos Regionais/economia , Programas Médicos Regionais/estatística & dados numéricos , Adulto , Idoso , Neoplasias Encefálicas/mortalidade , Craniotomia/mortalidade , Feminino , Número de Leitos em Hospital/economia , Número de Leitos em Hospital/estatística & dados numéricos , Mortalidade Hospitalar , Humanos , Tempo de Internação/economia , Tempo de Internação/estatística & dados numéricos , Masculino , Maryland , Pessoa de Meia-Idade , Estudos Retrospectivos , Carga de Trabalho/economia , Carga de Trabalho/estatística & dados numéricos
20.
J Neurosurg Spine ; 12(2): 178-82, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20121353

RESUMO

OBJECT: The most common spinal procedure performed in the US is lumbar discectomy for disc herniation. Longterm disc degeneration and height loss occur in many patients after lumbar discectomy. The incidence of mechanical back pain following discectomy varies widely in the literature, and its associated health care costs are unknown. The authors set out to determine the incidence of and the health care costs associated with mechanical back pain attributed to segmental degeneration or instability at the level of a prior discectomy performed at their institution. METHODS: The authors retrospectively reviewed the data for 111 patients who underwent primary, single-level lumbar hemilaminotomy and discectomy for radiculopathy. All diagnostic modalities, conservative therapies, and operative treatments used for the management of postdisectomy back pain were recorded. Institutional billing and accounting records were reviewed to determine the billed costs of all diagnostic and therapeutic measures. RESULTS: At a mean follow-up of 37.3 months after primary discectomy, 75 patients (68%) experienced minimal to no back pain, 26 (23%) had moderate back pain requiring conservative treatment only, and 10 (9%) suffered severe back pain that required a subsequent fusion surgery at the site of the primary discectomy. The mean cost per patient for conservative treatment alone was $4696. The mean cost per patient for operative treatment was $42,554. The estimated cost of treatment for mechanical back pain associated with postoperative same-level degeneration or instability was $493,383 per 100 cases of first-time, single-level lumbar discectomy ($4934 per primary discectomy). CONCLUSIONS: Postoperative mechanical back pain associated with same-level degeneration is not uncommon in patients undergoing single-level lumbar discectomy and is associated with substantial health care costs.


Assuntos
Dor nas Costas/economia , Dor nas Costas/epidemiologia , Discotomia/efeitos adversos , Custos de Cuidados de Saúde , Vértebras Lombares/cirurgia , Radiculopatia/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Dor nas Costas/etiologia , Dor nas Costas/terapia , Feminino , Seguimentos , Humanos , Incidência , Deslocamento do Disco Intervertebral/cirurgia , Laminectomia/efeitos adversos , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/economia , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/terapia , Radiografia , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
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