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1.
AJNR Am J Neuroradiol ; 27(6): 1258-71, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16775277

RESUMO

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) and white matter tractography (WMT) are promising techniques for estimating the course, extent, and connectivity patterns of the white matter (WM) structures in the human brain. In this study, DTI and WMT were used to evaluate WM tract reorganization after the surgical resection of brain tumors and vascular malformations. METHODS: Pre- and postoperative DTI data were obtained in 6 patients undergoing surgical resection of brain lesions. WMT using a tensor deflection algorithm was used to reconstruct WM tracts adjacent to the lesions. Reconstructed tracts included corticospinal tracts, the corona radiata, superior longitudinal and inferior fronto-occipital fasciculi, cingulum bundles, and the corpus callosum. RESULTS: WMT revealed a series of tract alteration patterns including deviation, deformation, infiltration, and apparent tract interruption. In general, the organization of WM tracts appeared more similar to normal anatomy after resection, with either disappearance or reduction of the deviation, deformation, or infiltration present preoperatively. In patients whose lesions were associated with corticospinal tract involvement, the WMT reconstructions showed that the tract was preserved during surgery and improved in position and appearance, and this finding correlated with improvement or preservation of motor function as determined by clinical assessment. CONCLUSION: WMT is useful for appreciating the complex relationships between specific WM structures and the anatomic distortions created by brain lesions. Further studies with intraoperative correlation are necessary to confirm these initial findings and to determine WMT utility for presurgical planning and evaluation of surgical treatments.


Assuntos
Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Encéfalo/patologia , Imagem de Difusão por Ressonância Magnética , Malformações Arteriovenosas Intracranianas/patologia , Malformações Arteriovenosas Intracranianas/cirurgia , Adolescente , Adulto , Criança , Pré-Escolar , Humanos , Processamento de Imagem Assistida por Computador , Pessoa de Meia-Idade , Tratos Piramidais/patologia
2.
J Cereb Blood Flow Metab ; 12(6): 1039-48, 1992 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-1328263

RESUMO

The maturation of brain oxidative capacity was studied in kittens, using cytochrome oxidase histochemistry, at different ages throughout development. Optical densitometry values of reacted tissue were obtained for 50 different structures of the brain. In general, most structures reached adult levels of oxidative capacity by 30 days of age with some motor areas (e.g., cerebellum, red nucleus) exhibiting adult values as early as 7 days of age. Thereafter, some structures (e.g., basal ganglia, thalamus) exhibited levels of cytochrome oxidase activity that exceeded adult values for varying periods of time. These findings indicate regional heterogeneity in the maturation of cerebral oxidative capacity. Furthermore, these maturational patterns appear to correlate well with previous observations from anatomical, physiological and neurobehavioral studies.


Assuntos
Cerebelo/metabolismo , Córtex Cerebral/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/análise , Animais , Tronco Encefálico/crescimento & desenvolvimento , Tronco Encefálico/metabolismo , Gatos , Cerebelo/crescimento & desenvolvimento , Córtex Cerebral/crescimento & desenvolvimento , Feminino , Masculino , Oxirredução , Tálamo/crescimento & desenvolvimento , Tálamo/metabolismo
3.
Cancer Gene Ther ; 6(2): 155-62, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10195882

RESUMO

More than half of malignant gliomas reportedly have alterations in the p53 tumor suppressor gene. Because p53 plays a key role in the cellular response to DNA-damaging agents, we investigated the role of p53 gene therapy before ionizing radiation in cultured human glioma cells containing normal or mutated p53. Three established human glioma cell lines expressing the wild-type (U87 MG, p53wt) or mutant (A172 and U373 MG, p53mut) p53 gene were transduced by recombinant adenoviral vectors bearing human p53 (Adp53) and Escherichia coli beta-galactosidase genes (AdLacZ, control virus) before radiation (0-20 Gy). Changes in p53, p21, and Bax expression were studied by Western immunoblotting, whereas cell cycle alterations and apoptosis were investigated by flow cytometry and nuclear staining. Survival was assessed by clonogenic assays. Within 48 hours of Adp53 exposure, all three cell lines demonstrated p53 expression at a viral multiplicity of infection of 100. p21, which is a p53-inducible downstream effector gene, was overexpressed, and cells were arrested in the G1 phase. Bax expression, which is thought to play a role in p53-induced apoptosis, did not change with either radiation or Adp53. Apoptosis and survival after p53 gene therapy varied. U87 MG (p53wt) cells showed minimal apoptosis after Adp53, irradiation, or combined treatments. U373 MG (p53mut) cells underwent massive apoptosis and died within 48 hours of Adp53 treatment, independent of irradiation. Surprisingly, A172 (p53mut) cells demonstrated minimal apoptosis after Adp53 exposure; however, unlike U373 MG cells, apoptosis increased with radiation dose. Survival of all three cell lines was reduced dramatically after >10 Gy. Although Adp53 transduction significantly reduced the survival of U373 MG cells and inhibited A172 growth, it had no effect on the U87 MG cell line. Transduction with AdLacZ did not affect apoptosis or cell cycle progression and only minimally affected survival in all cell lines. We conclude that responses to p53 gene therapy are variable among gliomas and most likely depend upon both cellular p53 status and as yet ill-defined downstream pathways involving activation of cell cycle regulatory and apoptotic genes.


Assuntos
Genes p53/genética , Terapia Genética/métodos , Glioma/radioterapia , Glioma/terapia , Proteínas Proto-Oncogênicas c-bcl-2 , Adenoviridae/genética , Apoptose , Western Blotting , Ciclo Celular , Núcleo Celular/metabolismo , Terapia Combinada , Relação Dose-Resposta à Radiação , Citometria de Fluxo , Vetores Genéticos , Humanos , Proteínas Proto-Oncogênicas/metabolismo , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2
4.
Int J Radiat Oncol Biol Phys ; 39(2): 445-54, 1997 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-9308949

RESUMO

PURPOSE: The median survival of well-selected patients with single-brain metastases treated with whole-brain irradiation and resection or radiosurgery is comparable, although a randomized trial of these two modalities has not been performed. In this era of cost containment, it is imperative that health-care professionals make fiscally prudent decisions. The present environment necessitates a critical appraisal of apparently equi-efficacious therapeutic modalities, and it is within this context that we present a comparison of the actual costs of resection and radiosurgery for brain metastases. METHODS AND MATERIALS: Survival and quality of life outcome data for radiation alone or with surgery were obtained from two randomized trials, and radiosurgical results were obtained from a multiinstitutional analysis that specifically evaluated patients meeting surgical criteria. Only linear accelerator radiosurgery data were considered. Cost analysis was performed from a societal view point, and the following parameters were evaluated: actual cost, cost ratios, cost effectiveness, incremental cost effectiveness, cost utility, incremental cost utility, and national cost burden. The computerized billing records for all patients undergoing resection or radiosurgery for single-brain metastases from January 1989 to July 1994 were reviewed. A total of 46 resections and 135 radiosurgery procedures were performed. During the same time period, 454 patients underwent whole-brain radiation alone. An analysis of the entire bill was performed for each procedure, and each itemized cost was assigned a proportionate figure. The relative cost ratios of resection and radiosurgery were compared using the Wilcoxon rank sum test. Cost effectiveness of each modality, defined as the cost per year of median survival, was evaluated. Incremental cost effectiveness, defined as the additional cost per year of incremental gain in median survival, compared to the next least expensive modality, was also determined. To calculate the societal or national impact of these practices, the proportion of patients potentially eligible for aggressive management was estimated and the financial impact was determined using various utilization ratios for radiosurgery and surgery. RESULTS: Both resection and radiosurgery yielded superior survival and functional independence, compared to whole brain radiotherapy alone, with minor differences in outcome between the two modalities; resection resulted in a 1.8-fold increase in cost, compared to radiosurgery. The latter modality yielded superior cost outcomes on all measures, even when a sensitivity analysis of up to 50% was performed. A reversal estimate indicated that in order for surgery to yield equal cost effectiveness, its cost would have to decrease by 48% or median survival would have to improve by 108%. The average cost per week of survival was $310 for radiotherapy, $524 for resection plus radiation, and $270 for radiosurgery plus radiation. CONCLUSIONS: For selected patients, aggressive strategies such as resection or radiosurgery are warranted, as they result in improved median survival and functional independence. Radiosurgery appears to be the more cost-effective procedure.


Assuntos
Neoplasias Encefálicas/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Pesquisa sobre Serviços de Saúde/métodos , Radiocirurgia/economia , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Análise Custo-Benefício/métodos , Humanos , Anos de Vida Ajustados por Qualidade de Vida , Radioterapia/economia , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Sensibilidade e Especificidade , Análise de Sobrevida , Estados Unidos
5.
J Neuroimmunol ; 120(1-2): 19-24, 2001 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-11694315

RESUMO

The immune-privileged status of the central nervous system is thought to limit the application of immunotherapy for treatment of malignant brain tumors. Because the Fas pathway has been proposed to play a role in immune evasion, we examined the effect of tumor environment on the expression of Fas ligand (FasL) in a mouse glioma model. Immunoblotting revealed the expression of membrane-bound FasL to nearly double when murine G26 gliomas were propagated intracranially (IC) as compared to subcutaneously (SC). Further analysis by flow cytometry revealed microglia, which were absent in the SC tumors, to account for half of the FasL expression in the IC tumors. Interestingly, when FasL activity was inhibited in IC tumors, the proportion of tumor-infiltrating leukocytes increased three-fold, reaching the same frequency as the SC tumors. These observations suggest that microglia are a major source of FasL expression in brain tumors and possibly contribute to the local immunosuppressive milieu of malignant gliomas.


Assuntos
Neoplasias Encefálicas/imunologia , Resistencia a Medicamentos Antineoplásicos/imunologia , Glioma/imunologia , Vigilância Imunológica/imunologia , Imunossupressores/metabolismo , Glicoproteínas de Membrana/imunologia , Microglia/imunologia , Animais , Anticorpos Monoclonais/farmacologia , Antígenos de Superfície/imunologia , Barreira Hematoencefálica/imunologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Movimento Celular/imunologia , Proteína Ligante Fas , Citometria de Fluxo , Lobo Frontal/imunologia , Lobo Frontal/metabolismo , Lobo Frontal/cirurgia , Glioma/tratamento farmacológico , Glioma/metabolismo , Gliose/imunologia , Tolerância Imunológica , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/patologia , Glicoproteínas de Membrana/antagonistas & inibidores , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL/imunologia , Camundongos Endogâmicos C57BL/metabolismo , Camundongos Endogâmicos C57BL/cirurgia , Microglia/metabolismo , Microglia/patologia , Falha de Tratamento , Células Tumorais Cultivadas/imunologia , Células Tumorais Cultivadas/metabolismo , Células Tumorais Cultivadas/transplante
6.
Microsc Res Tech ; 54(2): 106-13, 2001 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-11455617

RESUMO

Microglia, a type of differentiated tissue macrophage, are considered to be the most plastic cell population of the central nervous system (CNS). In response to pathological conditions, resting microglia undergo a stereotypic activation process and become capable of phagocytosis, antigen presentation, and lymphocyte activation. Considering their immune effector function, it is not surprising to see microglia accumulation in almost every CNS disease process, including malignant brain tumors or malignant gliomas. Although the function of these cells in CNS inflammatory processes is being studied, their role in malignant glioma biology remains unclear. On one hand, microglia may represent a CNS anti-tumor response, which is inactivated by local secretion of immunosuppressive factors by glioma cells. On the other hand, taking into account that microglia are capable of secreting a variety of immunomodulatory cytokines, it is possible that they are attracted by gliomas to promote tumor growth. A better understanding of microglia-glioma interaction will be helpful in designing novel immune-based therapies against these fatal tumors.


Assuntos
Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/fisiopatologia , Glioma/patologia , Glioma/fisiopatologia , Microglia/fisiologia , Animais , Humanos , Ratos
7.
AJNR Am J Neuroradiol ; 21(8): 1457-9, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11003278

RESUMO

Extracranial-intracranial (EC-IC) bypass may be necessary to facilitate treatment of unclippable posterior circulation fusiform aneurysms. Although intraoperative digital subtraction angiography (DSA) allows assessment of graft patency, this technique, because of difficulties inherent in performing selective catheterization and angiography in the operating room, has limitations. Duplex sonography, in contrast, is easily performed, and provides information regarding graft patency and blood flow direction during EC-IC bypass procedures. This latter information proved useful in determining the time of parent artery occlusion after two EC-IC bypass procedures performed for treatment of a fusiform midbasilar artery aneurysm.


Assuntos
Prótese Vascular , Revascularização Cerebral , Ultrassonografia Doppler Dupla , Grau de Desobstrução Vascular , Adulto , Encéfalo/patologia , Humanos , Período Intraoperatório , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Masculino
8.
AJNR Am J Neuroradiol ; 22(9): 1711-8, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11673166

RESUMO

BACKGROUND AND PURPOSE: Functional MR (fMR) imaging of word generation has been used to map Broca's area in some patients selected for craniotomy. The purpose of this study was to measure the reliability, precision, and accuracy of word-generation tasks to identify Broca's area. METHODS: The Brodmann areas activated during performance of word-generation tasks were tabulated in 34 consecutive patients referred for fMR imaging mapping of language areas. In patients performing two iterations of the letter word-generation tasks, test-retest reliability was quantified by using the concurrence ratio (CR), or the number of voxels activated by each iteration in proportion to the average number of voxels activated from both iterations of the task. Among patients who also underwent category or antonym word generation or both, the similarity of the activation from each task was assessed with the CR. In patients who underwent electrocortical stimulation (ECS) mapping of speech function during craniotomy while awake, the sites with speech function were compared with the locations of activation found during fMR imaging of word generation. RESULTS: In 31 of 34 patients, activation was identified in the inferior frontal gyri or middle frontal gyri or both in Brodmann areas 9, 44, 45, or 46, unilaterally or bilaterally, with one or more of the tasks. Activation was noted in the same gyri when the patient performed a second iteration of the letter word-generation task or second task. The CR for pixel precision in a single section averaged 49%. In patients who underwent craniotomy while awake, speech areas located with ECS coincided with areas of the brain activated during a word-generation task. CONCLUSION: fMR imaging with word-generation tasks produces technically satisfactory maps of Broca's area, which localize the area accurately and reliably.


Assuntos
Mapeamento Encefálico/métodos , Lobo Frontal/patologia , Idioma , Imageamento por Ressonância Magnética , Humanos , Reprodutibilidade dos Testes , Estudos Retrospectivos
9.
Neurosurgery ; 37(2): 214-8, 1995 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-7477771

RESUMO

Smaller posterior fossa (PF) volume has been suggested to be one of the mechanisms responsible for tonsillar herniation through the foramen magnum in patients with Chiari I malformation (CM I). Although previous radiological analyses of the cranial anatomy have suggested a smaller PF volume in patients with CM I, the relationship of the PF volume to decompressive surgery has not been reported. We have measured the ratio of PF volume to supratentorial volume (PF ratio [PFR]) in 20 patients with CM I and 20 control patients by retrospectively studying their magnetic resonance images with a computerized image analyzer. The mean PFR in patients with CM I (with or without syringomyelia) was significantly smaller than for those in the control group (15.6 +/- 1.9 versus 17.5 +/- 1.2, P = 0.0008). Although PFR did not correlate with the extent of tonsillar herniation in patients with CM I, it did directly correlate with their age, i.e., younger patients with CM I (but not control patients) had smaller PFRs. All but three patients responded both clinically and radiographically to decompressive surgery. Those patients who did not benefit from surgical intervention had normal PFRs. We conclude that: 1) PFRs are smaller in most patients with CM I; 2) a smaller PF may be a primary cause of tonsillar herniation; 3) patients with CM I who have smaller PFRs tend to develop symptoms earlier than those with normal values; 4) patients with smaller PFRs tend to respond better to suboccipital decompression.


Assuntos
Malformação de Arnold-Chiari/cirurgia , Imageamento por Ressonância Magnética , Adulto , Idoso , Idoso de 80 Anos ou mais , Malformação de Arnold-Chiari/diagnóstico , Doenças Cerebelares/cirurgia , Fossa Craniana Posterior/patologia , Fossa Craniana Posterior/cirurgia , Encefalocele/diagnóstico , Encefalocele/cirurgia , Feminino , Seguimentos , Herniorrafia , Humanos , Masculino , Pessoa de Meia-Idade , Exame Neurológico , Complicações Pós-Operatórias/diagnóstico , Estudos Retrospectivos , Siringomielia/patologia , Siringomielia/cirurgia
10.
Neurosurgery ; 46(4): 957-61; discussion 961-2, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10764271

RESUMO

OBJECTIVE: Although microglia have been suggested to be a component of the inflammatory reaction to tumors of the central nervous system, their role in glioma biology remains unknown. One obstacle to studying the function of microglia is the inability to effectively separate them from macrophages. Because flow cytometry can effectively discern immune cells with similar surface antigens, we evaluated its role in characterizing the mononuclear cell infiltration in experimental gliomas. METHODS: Freshly prepared rat C6, 9L, and RG-2 tumor specimens were labeled ex vivo with monoclonal antibodies against CD11b/c, CD45, and CD8a antigens and analyzed by flow cytometry. The extent of microglia (CD11b/c(high), CD45(low)), macrophage (CD11b/c(high), CD45(high)), and lymphocyte (CD11b/c(negative), CD45(high)) infiltration into tumors, tumor periphery, and contralateral tumor-free hemispheres was measured for each glioma type. RESULTS: Microglia, which accounted for 13 to 34% of viable cells, were distributed throughout the central nervous system and were present in the tumors, tumor periphery, and contralateral tumor-free hemispheres. In contrast, macrophages were less prominent within the tumors and tumor periphery (4.2-12%) and were scarce in the contralateral tumor-free hemispheres (0.9-1.1%). Among the tumor types, RG-2 gliomas had the least microglia/macrophage infiltration. The frequency and the distribution pattern of lymphocytes also varied among tumor models. Whereas lymphocytes accounted for more than one-third of the cells in C6 and 9L tumors, they represented only 1% of cells in RG-2 gliomas. CONCLUSION: More abundant than macrophages and scattered throughout the central nervous system, microglia account for a significant component of the inflammatory response to experimental gliomas. A better understanding of microglial function in gliomas may be important in the development of immunotherapy strategies.


Assuntos
Neoplasias Encefálicas/patologia , Glioma/patologia , Macrófagos/patologia , Animais , Citometria de Fluxo , Contagem de Linfócitos , Linfócitos do Interstício Tumoral/patologia , Microglia/patologia , Transplante de Neoplasias , Ratos , Ratos Endogâmicos F344 , Ratos Wistar
11.
Neurosurgery ; 44(5): 1077-82; discussion 1082-3, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10232541

RESUMO

OBJECTIVE: Considered as immune effector cells of the central nervous system, microglia represent a major component of the inflammatory cells found in malignant gliomas. Although their role in brain tumor biology is unclear, accumulation of microglia in malignant brain tumors may be mediated through active secretion of cytokines by glioma cells. Because hepatocyte growth factor/scatter factor (HGF/SF) has been shown to modulate glioma motility through an autocrine mechanism, and because microglia have been reported to express the HGF/SF receptor Met, we hypothesized that microglia recruitment by gliomas may also occur through the secretion of HGF/SF. METHODS: The effect of glioma cells in augmenting BV-2 murine microglia motility was studied by using an in vitro Boyden chamber migration assay. To determine the chemokines involved in microglia migration, neutralizing monoclonal antibodies against monocyte chemotactic protein-1 and HGF/SF were tested. Immunoblotting was used to check for the expression of HGF/SF by glioma cells, and the expression of Met by BV-2 cells was examined by flow cytometry. RESULTS: BV-2 migration was noted within 7 hours of incubation with both human (U251 MG and U373 MG) and murine (GL261) glioma cell lines. This migration corresponded to HGF/SF secretion by glioma cells and was completely inhibited by neutralizing monoclonal antibody against HGF/SF, but not monocyte chemotactic protein-1. Exposure of BV-2 cells to recombinant HGF/SF, but not monocyte chemotactic protein-1, resulted in their migration and down-regulation of Met in a dose-dependent fashion. CONCLUSION: HGF/SF, which plays a role in glioma motility and mitogenesis, may also act as a chemokine for microglia and may be responsible for the microglia infiltration in malignant gliomas. This active recruitment of microglia may play an important role in glioma biology.


Assuntos
Neoplasias Encefálicas/fisiopatologia , Glioma/fisiopatologia , Fator de Crescimento de Hepatócito/fisiologia , Microglia/fisiologia , Animais , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Movimento Celular/fisiologia , Glioma/metabolismo , Glioma/patologia , Fator de Crescimento de Hepatócito/biossíntese , Humanos , Camundongos , Proteínas Proto-Oncogênicas c-met/metabolismo , Proteínas Recombinantes , Células Tumorais Cultivadas
12.
Neurosurgery ; 35(5): 910-5; discussion 915-6, 1994 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7838341

RESUMO

The dismal results of conventional therapy for primary malignant brain tumors has justified exploring gene therapy approaches for this disease. Transduction of animal brain tumor models in vivo has been reported previously with retroviruses and herpes viruses. Because adenoviruses have the advantage of transducing quiescent and actively dividing tumor cells, they may prove to be more effective in such therapy. We used a replication-deficient recombinant adenovirus bearing the Escherichia coli beta-galactosidase gene in a rat C6 glioma tumor model. Transduced cells were detected by X-5-bromo-4-chloro-3-indolyl beta-D-galactoside staining to reveal beta-galactosidase activity. Initial experiments in vitro showed 50% and 90% transduction at vector titers of approximately 10(7) and 10(8) plaque-forming units/ml, respectively. Although no cytopathic effects were seen at 10(7) plaque-forming units/ml, more than 50% reduction in tumor cell growth was noted at 10(8) plaque-forming units/ml both in vitro and in vivo. Stereotactic delivery of the recombinant adenovirus into the frontal lobe of normal rat brains resulted in intense staining of all cell types, that is, neurons, astrocytes, and ependymal cells. Stereotactic injection into C6 glioma brain tumors in rats stained 25 to 30% of the tumor cells. We conclude that adenovirus vectors can be used to transfer genes to central nervous system tumors in vivo. Using stereotactic delivery, adenovirus vectors can transfer genes into the central nervous system intended for tumor therapy.


Assuntos
Adenoviridae/genética , Neoplasias Encefálicas/terapia , Transformação Celular Viral/genética , Vírus Defeituosos/genética , Terapia Genética/métodos , Glioma/terapia , Técnicas Estereotáxicas , Animais , Encéfalo/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Divisão Celular/genética , Linhagem Celular Transformada , Escherichia coli/genética , Feminino , Técnicas de Transferência de Genes , Glioma/genética , Glioma/patologia , Transplante de Neoplasias , Ratos , Ratos Wistar , Células Tumorais Cultivadas/patologia , beta-Galactosidase/genética
13.
J Neurosurg ; 93(4): 711-4, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11014555

RESUMO

The authors evaluated the role of titanium mesh used in combination with vascularized pericranium to provide rigid support during reconstruction of anterior skull base defects. Thirteen patients with large anterior skull base defects caused by tumor invasion or traumatic injury involving the cribriform plate, orbital roof, and planum sphenoidale were included in the study. The reconstruction technique involved placement of titanium mesh between two layers of continuous vascularized pericranium. Surgical glue and routine lumbar cerebrospinal fluid (CSF) drainage were not used in any patient. At a mean postoperative follow-up time of 22 months (range 8-39 months), none of the patients had developed infection or meningocele. Postoperative CSF rhinorrhea occurred in two patients with extensive dural defects, which resolved with temporary lumbar drainage. Use of titanium mesh and a two-layer vascularized pericranial graft is a safe, reproducible, and feasible method for reconstructing the anterior skull base. Patients with large dural defects may need temporary CSF diversion to avoid postoperative fistula formation.


Assuntos
Procedimentos de Cirurgia Plástica/métodos , Base do Crânio/anormalidades , Telas Cirúrgicas , Titânio , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Crânio/transplante , Base do Crânio/cirurgia
14.
J Neurosurg ; 88(5): 870-3, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9576256

RESUMO

OBJECT: The goal of this study was to evaluate gene delivery to a benign brain tumor. METHODS: A recombinant adenovirus vector bearing the Escherichia coli beta-galactosidase reporter gene was selectively injected into the vascular supply of a spontaneously occurring canine olfactory groove meningioma. The tumor and a small amount of peritumoral brain tissue were removed 5 days after viral injection and stained with X-Gal to assess gene delivery. The authors noted significant beta-galactosidase gene expression by the tumor, but not by surrounding brain tissue. No obvious viral-related cytotoxicity was noted. CONCLUSIONS: The authors found that meningiomas can be successfully transduced by adenovirus vectors by using endovascular techniques.


Assuntos
Terapia Genética , Neoplasias Meníngeas/veterinária , Meningioma/veterinária , Adenoviridae/genética , Animais , Corantes , DNA Recombinante/genética , Cães , Escherichia coli/genética , Osso Etmoide/patologia , Feminino , Galactosídeos , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Genes Reporter/genética , Vetores Genéticos , Indóis , Injeções Intra-Arteriais , Neoplasias Meníngeas/irrigação sanguínea , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/cirurgia , Neoplasias Meníngeas/terapia , Meningioma/irrigação sanguínea , Meningioma/patologia , Meningioma/cirurgia , Meningioma/terapia , Transdução Genética , beta-Galactosidase/genética
15.
J Neurosurg ; 93(4): 634-9, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11014542

RESUMO

OBJECT: Commonly used for management of cerebral edema in patients with brain tumors, steroid medications also have immunosuppressive functions. To characterize the effects of steroids on the central nervous system's response to tumors more clearly, flow cytometry was used to quantify the extent of inflammatory cell infiltration in an immunogenic rat glioma model. METHODS: Freshly prepared 11-day-old intracranial C6 tumors that had been excised from dexamethasone-treated and untreated rats were labeled ex vivo with monoclonal antibodies against CD 11b/c, CD45, and CD8a antigens. The extent of microglia (CD11b/c-highly positive, CD45-slightly positive cell), macrophage (CD11b/c-highly positive, CD45-highly positive cell), lymphocyte (CD11b/c-negative, CD45-highly positive cell), and cytotoxic T-cell (CD8a-positive cell) infiltration into each rat's tumor, tumor periphery, and contralateral tumor-free hemisphere was analyzed using flow cytometry. Microglia and lymphocytes constituted a significant component of infiltrating cells in this model, comprising 23 +/- 3% and 33 +/- 5% of viable cells, respectively. Macrophages, on the other hand, accounted for only 9 +/- 1% of infiltrating cells. Treatment of rats with a 7-day course of low-dose dexamethasone (0.1 mg/kg/day) resulted in a greater than 50% inhibition of microglia (p = 0.03) and lymphocyte (p = 0.001) infiltration into tumors. Increasing the dexamethasone dose to 1 mg/kg/day further abolished lymphocyte infiltration (89% inhibition, p = 0.001) but had no additional inhibitory effect on microglia invasion. Macrophage infiltration of tumors was not inhibited at the dexamethasone doses used in this study (p = 0.42). CONCLUSIONS: Flow cytometry is a valuable technique for characterizing tumor-associated inflammatory cells in gliomas. Even at low doses, dexamethasone was found to inhibit significantly the infiltration of brain tumors by lymphocytes and microglia. These findings should be considered when experimental immunotherapeutic strategies are evaluated for clinical application.


Assuntos
Anti-Inflamatórios/farmacologia , Neoplasias Encefálicas/imunologia , Dexametasona/farmacologia , Glioma/imunologia , Microglia/efeitos dos fármacos , Animais , Anti-Inflamatórios/imunologia , Anticorpos Monoclonais , Neoplasias Encefálicas/tratamento farmacológico , Dexametasona/imunologia , Citometria de Fluxo , Glioma/tratamento farmacológico , Linfócitos/imunologia , Macrófagos/imunologia , Microglia/imunologia , Ratos
16.
Neurol Res ; 17(3): 209-16, 1995 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7643977

RESUMO

Adenoviral vectors have recently been shown to effectively deliver genes into a variety of tissues. Since these vectors have some advantages over the more extensively investigated retroviruses, we studied the effect of two replication-defective adenovectors bearing human wild type tumor suppressor gene p53 (Adp53) and Escherichia coli beta-galactosidase gene (AdLacZ) on 9L glioma cells. Successful in vitro gene transfer was shown by DNA polymerase chain reaction (PCR), and expression was confirmed by reverse transcriptase RNA PCR and Western blot analyses. Transduction of 9L cells with the Adp53 inhibited cell growth and induced phenotypic changes consistent with cell death at low titers, while AdLacZ caused cytopathic changes only at high titers. Stereotactic injection of AdLacZ (10(7) plaque forming units) into tumor bed stained 25 to 30% of tumor cells at the site of vector delivery. Injection of Adp53 (10(7) plaque forming units), but not AdLacZ (controls), into established 4-day old 9L glioma brain tumors decreased tumor volume by 40% after 14 days. As a step toward gene therapy of brain tumors using replication-defective adenoviruses, these data support the use of tumor suppressor gene transfer for in vivo treatment of whole animal brain tumor models.


Assuntos
Adenoviridae/genética , Neoplasias Encefálicas/terapia , Genes p53 , Terapia Genética , Glioma/terapia , Animais , Escherichia coli/genética , Ratos , beta-Galactosidase/genética
17.
Magn Reson Imaging ; 19(8): 1129-32, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11711238

RESUMO

Functional magnetic resonance imaging (fMRI) was requested to assist in the evaluation of a comatose 38-year-old woman who had sustained multiple cerebral contusions from a motor vehicle accident. Previous electrophysiologic studies suggested absence of thalamocortical processing in response to median nerve stimulation. Whole-brain fMRI was performed utilizing visual, somatosensory, and auditory stimulation paradigms. Results demonstrated intact task-correlated sensory and cognitive blood oxygen level dependent (BOLD) hemodynamic response to stimuli. Electrodiagnostic studies were repeated and evoked potentials indicated supratentorial recovery in the cerebrum. At 3-months post trauma the patient had recovered many cognitive & sensorimotor functions, accurately reflecting the prognostic fMRI evaluation. These results indicate that fMRI examinations may provide a useful evaluation for brain function in non-responsive brain trauma patients.


Assuntos
Coma Pós-Traumatismo da Cabeça/diagnóstico , Imageamento por Ressonância Magnética , Acidentes de Trânsito , Adulto , Encéfalo/fisiopatologia , Coma Pós-Traumatismo da Cabeça/fisiopatologia , Feminino , Humanos , Prognóstico
18.
Otol Neurotol ; 22(5): 696-700, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11568682

RESUMO

OBJECTIVE: The exact mechanism of hearing loss, the most common presenting symptom in patients with vestibular schwannomas, remains unclear. To test whether increased pressure in the internal auditory canal from tumor growth is responsible for this clinical finding, the intracanalicular pressure in patients harboring these tumors was measured. STUDY DESIGN: Prospective study. SETTING: Tertiary referral hospital. PATIENTS: Fifteen consecutive patients undergoing a retrosigmoid approach for resection of vestibular schwannomas were included in the study. INTERVENTION: The intracanalicular pressure in every patient was measured by introducing a pressure microsensor into the internal auditory canal. The pressure readings, which were performed before tumor resection, were then correlated with tumor size and respective preoperative hearing status. RESULTS: Placement of the pressure monitor into the internal auditory canal revealed a biphasic waveform in every patient. Whereas the mean intracanalicular pressure was 20 mm Hg, there was significant variability among patients (range, 1-45 mm Hg). The intracanalicular pressure directly correlated with the amount of tumor in the internal auditory canal (r > 0.63, p < 0.012) but not with the total tumor size (r 0.075). Furthermore, eight patients with class A preoperative hearing (American Academy of Otolaryngology-Head and Neck Surgery classification) had lower intracanalicular pressures than did five patients with class B hearing (16 +/- 5 vs. 28 +/- 4). Although this observation suggested an inverse correlation between the intracanalicular pressure and hearing function, the difference between the two groups was not statistically significant (p = 0.14). CONCLUSION: Pressure on the cochlear nerve as a result of tumor growth in the internal auditory canal may be responsible for hearing loss in patients with vestibular schwannomas. Modification of surgical techniques to address the elevated intracanalicular pressure may be beneficial in improving hearing preservation in these patients.


Assuntos
Orelha Interna/patologia , Neuroma Acústico/patologia , Nervo Coclear/fisiopatologia , Doenças dos Nervos Cranianos/etiologia , Doenças dos Nervos Cranianos/fisiopatologia , Humanos , Neuroma Acústico/complicações , Estudos Prospectivos , Teste do Limiar de Recepção da Fala
19.
Surg Neurol ; 45(4): 383-4, 1996 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8607091

RESUMO

BACKGROUND: Depression of the temporal fossa that is often caused by atrophy of the temporalis muscle or superficial temporal fat pad may be an unavoidable defect following pterional craniotomy. Various techniques have been previously described to correct this disfiguring defect. Most techniques, however, require drilling holes into the cranium or the synthetic grafts for attachment of the temporalis muscle. METHODS: A simple method is described by which a temporal fossa depression is repaired with methylmethacrylate bone cement and a new superior temporal line is created for attachment of the temporalis muscle without the need to drill suture holes into the acrylic or the cranium. RESULTS AND CONCLUSIONS: The technique described has been used on several patients with excellent cosmetic outcome.


Assuntos
Craniotomia/efeitos adversos , Cirurgia Plástica , Osso Temporal/patologia , Músculo Temporal/cirurgia , Humanos , Crânio/cirurgia , Retalhos Cirúrgicos , Músculo Temporal/patologia
20.
Surg Neurol ; 53(2): 168-72; discussion 172-3, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10713196

RESUMO

BACKGROUND: Submucosal dissection of the nasal septum is often performed as part of the transseptal approach to the sella. To evaluate whether this submucosal dissection is a necessary component of this operation, we compared the morbidity of a direct transmucosal endonasal approach to that of the transseptal approach in patients undergoing pituitary surgery. METHODS: Forty-one consecutive patients undergoing pituitary surgery from January 1996 to March 1999 were included in this study. The first 21 patients underwent the standard transseptal operation through either a sublabial or columellar incision. The latter 20 patients were operated on through an endoscopically guided, direct endonasal exposure, without any submucosal dissection of the nasal septum. The operative morbidity, the duration of surgery, and the length of hospitalization for each group were compared. RESULTS: The sphenoid sinus exposure obtained through the endonasal route was comparable with the transseptal approach and was adequate for resection of most pituitary tumors. Although the morbidity of the two approaches was similar, patients undergoing the endonasal operation had less postoperative facial pain. Furthermore, the endonasal approach significantly decreased the length of the operation (116 minutes vs. 161 minutes, p = 0.002) and the duration of hospitalization (3.6 vs. 5.1 days, p = 0.003) as compared with the transseptal route. CONCLUSIONS: Morbidity of the endonasal approach to the sphenoid sinus is comparable to that of a conventional transseptal approach. By eliminating the submucosal dissection, the endonasal approach reduces postoperative facial discomfort and decreases length of surgery and hospitalization.


Assuntos
Endoscopia/métodos , Procedimentos Neurocirúrgicos/métodos , Nariz/cirurgia , Neoplasias Hipofisárias/cirurgia , Adenoma/cirurgia , Adulto , Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/cirurgia , Cistos do Sistema Nervoso Central/cirurgia , Craniofaringioma/cirurgia , Feminino , Fibrose/cirurgia , Germinoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/instrumentação , Resultado do Tratamento
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