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1.
Ann Oncol ; 18(11): 1851-5, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17804469

RESUMO

BACKGROUND: Primary intraocular lymphoma (PIOL) is an uncommon subset of primary central nervous system lymphoma. Because it is rare and difficult to diagnose, the natural history and optimal management are unknown. PATIENTS AND METHODS: A retrospective study of 83 HIV negative, immunocompetent PIOL patients was assembled from 16 centers in seven countries. RESULTS: Median age at diagnosis was 65. Median ECOG performance status was 0. Presenting symptoms included blurred vision, decreased visual acuity, and floaters. Median time to diagnosis was 6 months. Diagnosis was made by vitrectomy (74), choroidal/retinal biopsy (6) and ophthalmic exam (3). Eleven percent had positive CSF cytology. Initial treatment was categorized as focal in 23 (intra-ocular methotrexate, ocular radiotherapy) or extensive in 53 (systemic chemotherapy, whole brain radiotherapy). Six received none; details are unknown in one. Forty-seven relapsed: brain 47%, eyes 30%, brain and eyes 15%, and systemic 8%. Median time to relapse was 19 months. Focal therapy alone did not increase risk of brain relapse. Median progression free (PFS) and overall survival (OS) were 29.6 and 58 months, respectively, and unaffected by treatment type. CONCLUSION: Treatment type did not affect relapse pattern, median PFS or OS. Focal therapy may minimize treatment toxicity without compromising disease control.


Assuntos
Neoplasias Oculares/mortalidade , Neoplasias Oculares/patologia , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/patologia , Recidiva Local de Neoplasia/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias do Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/terapia , Terapia Combinada , Consenso , Neoplasias Oculares/terapia , Feminino , Soronegatividade para HIV , Humanos , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
2.
AJNR Am J Neuroradiol ; 27(3): 715-21, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16552023

RESUMO

The blood-brain barrier (BBB) presents a major obstacle to the treatment of malignant brain tumors and other central nervous system (CNS) diseases. The Eleventh Annual Blood-Brain Barrier Disruption Consortium Meeting was convened to discuss recent advances and future directions in imaging and nanomedicine. Two sessions, one on Cell and Molecular Imaging in the CNS and another on Nanotechnology, Nanobiology, and Nanomedicine, were held March 17-18, 2005, in Portland, Ore. CNS imaging presentations targeted differentiating tumor, neural lesions, and necrosis from healthy brain tissue; methods of delivery of imaging agents across the BBB; and new iron oxide-based nanoparticle contrast agents for MR imaging. Nanobiology presentations covered the development of new nanotechnology and its use in imaging, diagnosis, and therapy in the CNS. Discussions at this meeting stressed the role of biotechnology in the convergence of CNS imaging and nanomedicine and are summarized in this article.


Assuntos
Barreira Hematoencefálica , Doenças do Sistema Nervoso Central/diagnóstico , Doenças do Sistema Nervoso Central/terapia , Nanomedicina , Diagnóstico por Imagem , Humanos
3.
AJNR Am J Neuroradiol ; 22(5): 818-23, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11337321

RESUMO

BACKGROUND AND PURPOSE: Optic pathway and/or hypothalamic astrocytomas in children are often quiescent, but in some cases, more aggressive tumors may cause progressive visual, endocrine, and neurologic deterioration. The initial treatment of these gliomas includes surgery and IV chemotherapy. Radiotherapy is not recommended in young children because of its severe adverse effects on cognitive and neuroendocrine function. This report suggests a new approach using combined intraarterial and IV carboplatin-based chemotherapy for patients for whom first line treatment has already failed. METHODS: Six children (mean age, 57 months) with the diagnosis of optic pathway hypothalamic gliomas, who had tumor progression after surgery and underwent IV chemotherapy, were treated monthly with intraarterially administered carboplatin, intraarterially administered etoposide phosphate, and IV administered Cytoxan. Four of the children had histologically verified pilocytic astrocytomas, and in two cases, diagnosis was made on the basis of clinical findings. Administration of the intraarterial chemotherapy required catheter placement in both internal carotid arteries at the level of C2-C3 and into one of the vertebral arteries at the level of C6-C7, with the patient under general anesthesia. RESULTS: Four of six patients had partial radiographic response, one had stable disease, and one had progressive disease after one cycle. Three patients showed clinical improvement. There were no serious complications associated with the angiographic procedures. Toxicities included bronchospasm that resolved after 3 to 4 minutes in one patient. One patient showed mild ototoxicity, and four patients needed platelet transfusion because of hematologic toxicity of drugs. CONCLUSION: These results suggest that this modality of chemotherapy (administered after failure of systemic [ie, IV] chemotherapy), of progressive optic-hypothalamic astrocytomas in young children may be an effective treatment prior to radiotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Glioma/tratamento farmacológico , Neoplasias Hipotalâmicas/tratamento farmacológico , Vias Visuais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/uso terapêutico , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Carboplatina/uso terapêutico , Criança , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Etoposídeo/uso terapêutico , Feminino , Glioma/diagnóstico , Humanos , Neoplasias Hipotalâmicas/diagnóstico , Lactente , Recém-Nascido , Infusões Intra-Arteriais , Injeções Intravenosas , Imageamento por Ressonância Magnética , Masculino , Resultado do Tratamento
4.
Neurosurgery ; 48(5): 1033-40; discussion 1040-1, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11334269

RESUMO

OBJECTIVE: The importance of enhanced drug delivery in patients with central nervous system (CNS) malignancies has not yet been demonstrated conclusively. Intra-arterial chemotherapy in combination with osmotic bloodbrain barrier disruption (BBBD) increases drug delivery to tumor by 2- to 5-fold and to surrounding brain tissue by 10- to 100-fold as compared with intravenous administration of chemotherapy. Primary CNS lymphoma (PCNSL) is an excellent model for studying dose intensity because PCNSL is a highly infiltrative, chemosensitive, primary CNS malignancy in which the integrity of the blood-brain barrier is highly variable. METHODS: Survival time was assessed in 74 non-acquired immunodeficiency syndrome patients with PCNSL who underwent a total of 1047 BBBD procedures. Total dose intensity is estimated by using the number of intraarterial infusions or a cumulative degree of BBBD score. RESULTS: Using proportional hazards multivariable analyses to adjust for baseline characteristics, survival was significantly associated with the total intensity of BBBD (P < 0.05). Additional statistical analyses demonstrate that survival bias does not fully explain these associations. Even when only patients who attained a complete response are considered, increased dose intensity resulted in increased survival. CONCLUSION: In patients with PCNSL, a chemotherapy-responsive tumor type, survival time is highly associated with total drug dose delivered, even in analyses designed to control for potential survival biases. These results probably constitute the strongest evidence to date of the importance of total dose intensity in treating CNS malignancies.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Linfoma/tratamento farmacológico , Antineoplásicos/administração & dosagem , Barreira Hematoencefálica , Neoplasias do Sistema Nervoso Central/fisiopatologia , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Humanos , Injeções Intra-Arteriais , Linfoma/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Análise de Sobrevida
5.
Clin Cancer Res ; 7(3): 493-500, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11297239

RESUMO

Carboplatin is effective in the treatment of malignant brain tumors. However, when administered in conjunction with osmotic opening of the blood-brain barrier (BBB), carboplatin is ototoxic. The purpose of this study was to determine whether delayed administration of sodium thiosulfate (STS), given after BBB closure, provided protection against carboplatin ototoxicity. Patients underwent monthly treatment with intra-arterial carboplatin (200 mg/m2/day x 2) in conjunction with osmotic opening of the BBB, for up to 1 year. Audiological assessment was conducted at baseline and within 24 h before each monthly treatment. STS was administered i.v. as one (20 g/m2) or two (20 g/m2 and 16 g/m2) 15-min doses, depending on baseline hearing status. The initial group received the first STS dose 2 h (or 2 and 6 h) after carboplatin (STS2) and a subsequent group received STS 4 h (or 4 and 8 h) after carboplatin (STS4). Audiological data were compared with a historical comparison group (HCG) treated with carboplatin without STS. Spearman correlation coefficients comparing STS 2 (n = 24), STS4 (n = 17), and HCG (n = 19) indicated significantly lower rates of ototoxicity with increased delay in STS (P = 0.0006). On the basis of the analysis of hearing levels, there were significant differences among the two STS groups and HCG at 8000 Hz (P = 0.0010) and at 4000 Hz (P = 0.0075). The log-rank test for time to ototoxicity indicated a significant difference between STS4 and HCG (P = 0.0018). Delayed STS was effective in protecting against carboplatin-induced hearing loss. STS delayed to 4 h after carboplatin significantly decreased time to development of ototoxicity and rate of ototoxicity when compared with HCG.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Carboplatina/efeitos adversos , Surdez/induzido quimicamente , Tiossulfatos/uso terapêutico , Adolescente , Adulto , Idoso , Barreira Hematoencefálica/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Fatores de Tempo
6.
Neuro Oncol ; 3(1): 46-54, 2001 01.
Artigo em Inglês | MEDLINE | ID: mdl-11305417

RESUMO

Therapeutic options for the treatment of malignant brain tumors have been limited, in part, because of the presence of the blood-brain barrier. For this reason, the Sixth Annual Meeting of the Blood-Brain Barrier Disruption Consortium, the focus of which was the "Importance of Dose Intensity in Neuro-Oncology Clinical Trials," was convened in April 2000, at Government Camp, Mount Hood, Oregon. This meeting, which was supported by the National Cancer Institute, the National Institute of Neurological Disorders and Stroke, and the National Institute of Deafness and Other Communication Disorders, brought together clinicians and basic scientists from across the U.S. to discuss the role of dose intensity and enhanced chemotherapy delivery in the treatment of malignant brain tumors and to design multicenter clinical trials. Optimizing chemotherapy delivery to the CNS is crucial, particularly in view of recent progress identifying certain brain tumors as chemosensitive. The discovery that specific constellations of genetic alterations can predict which tumors are chemoresponsive, and can therefore more accurately predict prognosis, has important implications for delivery of intensive, effective chemotherapy regimens with acceptable toxicities. This report summarizes the discussions, future directions, and key questions regarding dose-intensive treatment of primary CNS lymphoma, CNS relapse of systemic non-Hodgkin's lymphoma, anaplastic oligodendroglioma, high-grade glioma, and metastatic cancer of the brain. The promising role of cytoenhancers and chemoprotectants as part of dose-intensive regimens for chemosensitive brain tumors and development of improved gene therapies for malignant gliomas are discussed.


Assuntos
Antineoplásicos/administração & dosagem , Barreira Hematoencefálica/efeitos dos fármacos , Neoplasias Encefálicas/tratamento farmacológico , Soluções Hipertônicas/farmacologia , Neoplasias Meníngeas/tratamento farmacológico , Adulto , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Alquilantes/farmacocinética , Antineoplásicos Alquilantes/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doenças da Medula Óssea/induzido quimicamente , Transplante de Medula Óssea , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Butionina Sulfoximina/farmacologia , Butionina Sulfoximina/uso terapêutico , Criança , Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos Fase III como Assunto , Transtornos Cognitivos/etiologia , Terapia Combinada , Irradiação Craniana , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Terapia Genética , Vetores Genéticos/farmacocinética , Glioma/tratamento farmacológico , Glioma/metabolismo , Glutationa/metabolismo , Cobaias , Perda Auditiva Neurossensorial/induzido quimicamente , Perda Auditiva Neurossensorial/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/patologia , Neoplasias Meníngeas/fisiopatologia , Neoplasias Meníngeas/secundário , Neoplasias Meníngeas/terapia , Estudos Multicêntricos como Assunto/métodos , Neuroblastoma/tratamento farmacológico , Oligodendroglioma/tratamento farmacológico , Permeabilidade/efeitos dos fármacos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Resultado do Tratamento
7.
Clin Cancer Res ; 6(1): 309-15, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10656463

RESUMO

Platinum-based chemotherapeutic agents, such as carboplatin and cisplatin, are effective against many human tumors, but their use may be limited by a high incidence of ototoxicity. Delayed administration of the chemoprotective agent sodium thiosulfate (STS) reduces the ototoxicity of carboplatin in a guinea-pig model, when given up to 8 h after the chemotherapy, and also reduces hearing loss in patients given carboplatin with osmotic blood-brain barrier opening for treatment of brain tumors. We tested whether STS, given at times that achieved otoprotection, could impact the chemotherapeutic efficacy of carboplatin. The impact of STS was evaluated by measuring the onset of growth of LX-1 human small cell lung carcinoma s.c. xenografts in the nude rat. When STS was administered as two boluses, 2 and 6 h after treatment with carboplatin and etoposide, there was a decrease in the time to tumor progression. In contrast, when STS administration was delayed until 8 h after carboplatin/etoposide, there was no reduction in the antitumor cytotoxicity of the chemotherapy. STS infusion did not significantly affect ultrafilterable platinum pharmacokinetics in the guinea pig. To explore the potential wider applicability of STS, in a pilot study we tested its efficacy against cisplatin ototoxicity. Delayed administration of STS, 2 h after cisplatin, was protective against cisplatin-induced ototoxicity in the guinea pig model, as determined by electrophysiological measures. On the basis of these data, we suggest that delayed administration of STS may provide a mechanism to reduce the ototoxicity caused by administration of carboplatin or cisplatin for both central nervous system and systemic cancer chemotherapy.


Assuntos
Antídotos/uso terapêutico , Limiar Auditivo/efeitos dos fármacos , Carboplatina/toxicidade , Carboplatina/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Cisplatino/toxicidade , Neoplasias Pulmonares/tratamento farmacológico , Tiossulfatos/uso terapêutico , Animais , Antídotos/administração & dosagem , Carboplatina/farmacocinética , Esquema de Medicação , Orelha Média/efeitos dos fármacos , Orelha Média/patologia , Etoposídeo/toxicidade , Feminino , Cobaias , Humanos , Masculino , Ratos , Ratos Long-Evans , Ratos Nus , Tiossulfatos/administração & dosagem , Células Tumorais Cultivadas
8.
Neurosurgery ; 46(1): 51-60; discussion 60-1, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10626935

RESUMO

OBJECTIVE: Patients with non-acquired immunodeficiency syndrome-related primary central nervous system lymphomas have the potential to achieve durable complete responses without radiotherapy, with treatment using enhanced chemotherapy delivery with blood-brain barrier disruption (BBBD). Reported 5-year survival rates with combined chemotherapy and radiotherapy were generally only 9 to 22% and were associated, in one study, with an overall 32% incidence of overt dementia and ataxia, which are dramatically increased among patients more than 60 years of age. METHODS: At the Oregon Health Sciences University, 111 consecutive patients with non-acquired immunodeficiency syndrome-related central nervous system lymphomas were prospectively treated with methotrexate-based, BBBD-enhanced chemotherapy and underwent formal neuropsychological evaluations. Of those, 74 patients had no systemic lymphoma and had received no prior irradiation; those 74 patients are described in this report. RESULTS: The estimated 5-year survival rate for this group was 42%, and the median survival time was 40.7 months. Overall, 48 patients (65%) exhibited complete responses and 36 patients continued to exhibit complete responses after 1 year of BBBD-enhanced chemotherapy. Of those 36 patients, none demonstrated evidence of cognitive loss in neuropsychological tests and/or clinical examinations. CONCLUSION: BBBD-enhanced chemotherapy delivery, without subsequent radiotherapy, resulted in favorable survival and cognitive outcomes for patients with primary central nervous system lymphomas who had not previously undergone irradiation. A cooperative multicenter study of intravenous chemotherapy without radiotherapy versus BBBD-enhanced chemotherapy would address the feasibility and necessity of performing a Phase III study for these rare central nervous system malignancies.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Linfoma/tratamento farmacológico , Metotrexato/administração & dosagem , Barreira Hematoencefálica , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Prospectivos , Indução de Remissão , Fatores de Tempo
9.
Cancer ; 88(3): 637-47, 2000 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-10649259

RESUMO

BACKGROUND: The aim of this study was to determine the safety and efficacy of intraarterial chemotherapy with osmotic opening of the blood-brain barrier (BBB) for the treatment of malignant brain tumors when administered across multiple centers. METHODS: Patients with primary central nervous system lymphoma (PCNSL), primitive neuroectodermal tumor (PNET), germ cell tumor, cancer metastasis to the brain, or low or high grade glioma were eligible. Prior to entry, magnetic resonance imaging or computed tomography brain scan, medical history, neurologic status, and Karnofsky performance status were reviewed at the coordinating center. Standardized anesthesia and intraarterial catheterization guidelines were followed by a multidisciplinary team at each center. Between March 1994 and November 1997, 5 universities treated 221 adult patients with intraarterial chemotherapy with or without osmotic opening of the BBB (2464 procedures). RESULTS: Of evaluable patients with PCNSL, 40 of 53 (75%) achieved complete response (CR). All evaluable patients with PNET (n = 17), metastatic disease (n = 12), or germ cell tumor (n = 4) achieved stable disease (SD) or better. Of 57 evaluable patients with glioblastoma multiforme, 45 (79%) achieved SD or better. Asymptomatic subintimal tear occurred in 11 of 221 patients (5%), pulmonary embolism in 6 of 221 (2.7%), and renal toxicity in 4 of 221 (1.8%). One patient with extensive glioma expired within 48 hours after treatment. CONCLUSIONS: Using standard guidelines and protocols, intraarterial chemotherapy with or without osmotic opening of the BBB is feasible across multiple centers with a low incidence of catheter-related complications. In patients with chemotherapy-sensitive tumors, such as PCNSL, PNET, germ cell tumor, and cancer metastasis to the central nervous system, enhanced delivery results in a high degree of tumor response, with an efficacy profile that is reproducible across multiple centers.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Barreira Hematoencefálica/efeitos dos fármacos , Neoplasias Encefálicas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Encefálicas/secundário , Estudos de Viabilidade , Feminino , Germinoma/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Glioma/tratamento farmacológico , Humanos , Injeções Intra-Arteriais/efeitos adversos , Injeções Intra-Arteriais/instrumentação , Avaliação de Estado de Karnofsky , Linfoma/tratamento farmacológico , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tumores Neuroectodérmicos/tratamento farmacológico , Exame Neurológico , Osmose , Indução de Remissão , Reprodutibilidade dos Testes , Segurança , Tomografia Computadorizada por Raios X
10.
AJNR Am J Neuroradiol ; 20(10): 1794-802, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10588099

RESUMO

BACKGROUND AND PURPOSE: When the clinical and radiologic characteristics of an unusual cervical spinal cord complication of intra-arterial (IA) chemotherapy with blood brain-barrier (BBB) disruption in the vertebral circulation are documented. Seven cases are reported and analyzed in search of a pathophysiologic explanation. METHODS: We retrospectively identified 94 patients who received a total of 380 standardized regimens of IA carboplatin, IA or IV etoposide phosphate, and IV cyclophosphamide infusion in conjunction with osmotic BBB disruption of the vertebral artery. We describe seven of those patients in whom unexpected neck pain developed followed by neurologic symptoms primarily in the upper extremities. RESULTS: The symptoms correlated with MR abnormalities (T1 hypointensity, T2 hyperintensity, and unusual contrast enhancement) in the cervical spinal cord, usually involving the gray matter. The neurologic deficits and MR changes were generally transient. One patient who received a flu vaccination 48 hours before the chemotherapy incurred progressive myelitis and expired. CONCLUSION: The pathophysiology of this complication is probably multifactorial but may be related to vascular streaming and an atypical inflammatory toxic reaction to carboplatin and etoposide. The complication has not recurred during a 6-month period following modification of the protocol.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Barreira Hematoencefálica/efeitos dos fármacos , Neoplasias Encefálicas/tratamento farmacológico , Manitol/efeitos adversos , Medula Espinal/efeitos dos fármacos , Artéria Vertebral/efeitos dos fármacos , Adolescente , Adulto , Neoplasias Encefálicas/patologia , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Vértebras Cervicais/patologia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Humanos , Vacinas contra Influenza/efeitos adversos , Infusões Intra-Arteriais , Infusões Intravenosas , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mielite/induzido quimicamente , Mielite/diagnóstico , Exame Neurológico/efeitos dos fármacos , Estudos Retrospectivos , Medula Espinal/patologia , Artéria Vertebral/patologia
11.
Neurosurgery ; 44(3): 604-8; discussion 608-9, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10069598

RESUMO

DESPITE MAJOR ADVANCES in neuroscience, potential therapeutic options for the treatment of central nervous system diseases often cannot be optimized secondary to the presence of the blood-brain barrier (BBB). During the next decade of inquiry, it is crucial that basic science and clinical research that is focused on overcoming the BBB, to optimize delivery to the central nervous system, be identified and supported as a priority topic. For this reason, the third international Cerebrovascular Biology and Blood-Brain Barrier Conference was convened in March 1998 in Gleneden Beach, OR. This meeting brought together basic science and clinical researchers from around the world to analyze BBB function and to discuss delivery of effective agents to the central nervous system for treatment of brain disease. This report summarizes the information presented at the meeting and the discussions that ensued. The current state of knowledge, obstacles to further understanding the BBB, and research priorities are identified.


Assuntos
Barreira Hematoencefálica/fisiologia , Doenças do Sistema Nervoso Central/terapia , Biologia Molecular/tendências , Previsões , Humanos
12.
J Pharmacol Exp Ther ; 286(1): 77-84, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9655844

RESUMO

Sodium thiosulfate (STS) provides protection against carboplatin-induced ototoxicity in an animal model. The purpose of this study was to determine the STS dose required for otoprotection, in patients with malignant brain tumors treated with carboplatin in conjunction with osmotic blood-brain barrier disruption. Twenty-nine patients received STS intravenously 2 hr after carboplatin. Doses were escalated from 4 g/m2 to 8, 12, 16 and 20 g/m2 on consecutive months. Audiologic assessment was performed at baseline and monthly. The audiograms were compared with those of 19 similarly treated historical control patients who did not receive STS. The incidence of ototoxicity in the historical control group of patients was 79% (15/19). This group had an average loss of 20.8 +/- 5.9 dB (n = 19) at 8 kHz after one treatment with carboplatin, whereas the STS treatment group lost only 3.7 +/- 2 dB (n = 15) after one treatment. This difference was statistically significant as assessed by Student's t test (P < .05). Furthermore, patients in the STS treatment group with excellent base-line hearing showed little change in hearing thresholds at 8 kHz after the second treatment (8.0 +/- 8.3 dB) (n = 5) compared with the historical control patients with excellent base-line hearing, (40.5 +/- 8.6 dB) (n = 11). Our data support that doses of 16 or 20 g/m2 of STS decrease carboplatin-induced hearing loss without central nervous system entry. Clinical demonstration of an otoprotective effect with a two-compartment system to prevent drug-induced hearing loss, while preserving central nervous system cytotoxicity, has not been reported previously.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias Encefálicas/tratamento farmacológico , Carboplatina/efeitos adversos , Transtornos da Audição/prevenção & controle , Tiossulfatos/uso terapêutico , Adolescente , Adulto , Glicemia/análise , Barreira Hematoencefálica/efeitos dos fármacos , Criança , Relação Dose-Resposta a Droga , Feminino , Transtornos da Audição/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Tiossulfatos/efeitos adversos , Tiossulfatos/farmacocinética
13.
J Neurosci Nurs ; 30(2): 81-90, 1998 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9642616

RESUMO

Chemotherapy delivery for the treatment of malignant brain tumors is markedly enhanced when given in conjunction with osmotic opening of the blood-brain barrier. Osmotic opening or disruption of the blood-brain barrier is achieved while the patient is under general anesthesia, by the infusion of mannitol into the internal carotid or vertebral artery circulation. The mannitol infusion is followed by administration of intraarterial chemotherapy. A National Blood-Brain Barrier Program now exists and includes six universities. Within the National Program over 4200 blood-brain barrier disruption procedures have been performed in over 400 patients. Patients with primary central nervous system (CNS) lymphoma, glioma, primitive neuroectodermal tumor (PNET), germ cell and metastatic cancer are eligible for treatment. Results in patients with primary CNS lymphoma, recently reported in the Cancer Journal, include the first example of a durable response in a primary brain tumor without loss of cognitive function and without use of radiotherapy. Results with PNET and germ cell tumors are also very encouraging. Advanced practice nurses coordinate the care of blood-brain barrier disruption patients. Care includes patients selection, education, close neurological observation, maintenance of fluid and electrolyte balance and managing effects of high-dose chemotherapy. Both acute and long-term medical and psychological follow-up are an essential component of the program, as well as patient and family support.


Assuntos
Antineoplásicos/administração & dosagem , Barreira Hematoencefálica/efeitos dos fármacos , Neoplasias Encefálicas/tratamento farmacológico , Manitol/administração & dosagem , Antineoplásicos/efeitos adversos , Neoplasias Encefálicas/irrigação sanguínea , Neoplasias Encefálicas/enfermagem , Humanos , Infusões Intra-Arteriais , Manitol/efeitos adversos , Guias de Prática Clínica como Assunto , Equilíbrio Hidroeletrolítico/efeitos dos fármacos
14.
Cancer J Sci Am ; 4(2): 110-24, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9532413

RESUMO

PURPOSE: Radiographic tumor response and survival were evaluated in the pediatric and young adult population with germ cell tumor, primary CNS lymphoma, or primitive neuroectodermal tumor receiving intra-arterial carboplatin- or methotrexate-based chemotherapy with osmotic blood-brain barrier disruption (BBBD). PATIENTS AND METHODS: Thirty-four patients with histologically confirmed germ cell tumor (n = 9), primary CNS lymphoma (n = 9), or primitive neuroectodermal tumor (n = 16) were treated at the Oregon Health Sciences University from August 1981 through April 1995. Ages ranged from 1 to 30 years (mean, 18 years). Prior treatments included cranial radiation (n = 10) and chemotherapy (n = 18). All patients underwent extensive baseline neuropsychological evaluation and follow-up evaluation upon completion of the protocol, except for two patients who declined follow-up assessment. RESULTS: Six hundred and forty-five BBBD procedures were performed with no mortality. Significant complications included one episode of tonsillar herniation with no neurologic sequelae, 4% incidence of seizures, and 3% incidence of sepsis or granulocytopenic fever. Ototoxicity was seen in 61% of patients who received carboplatin chemotherapy. Eighty-two percent of the patients had an objective response to treatment, including 62% with complete response and 20% with partial response. For most patients, cognitive functioning was maintained or improved at follow-up; this pattern was statistically significant. Three of the test scores for the seven patients who did not receive radiation therapy showed a cognitive decline of at least one standard deviation. Among the nine patients who received radiation therapy before or after BBBD chemotherapy, 11 test scores showed a decline in cognitive function at one standard deviation or more. DISCUSSION: Durable responses were seen in patients with germ cell tumor and primary CNS lymphoma when treated with BBBD. Primitive neuroectodermal tumor requires post-chemotherapy radiotherapy for a durable response to be attained. Ototoxicity was a major form of toxicity in the patients who received carboplatin, but with the recent introduction of sodium thiosulfate, this problem has been markedly alleviated. Favorable cognitive outcomes appeared more likely for patients treated solely with BBBD chemotherapy and not with radiotherapy. Trends in the results for this sample are similar to those of previous research showing that radiotherapy is associated with cognitive decline. Current alternatives to enhanced drug delivery after BBBD include bone marrow transplantation; however, the increment in drug delivery is less, the number of courses is limited, and the morbidity and mortality are greater for bone marrow transplant than for BBBD. The current results suggest that in future trials, irradiation may not be needed in lymphoma and may not be necessary in some CNS germ cell tumors and that more focal radiotherapy should be further assessed in localized primitive neuroectodermal tumors.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Germinoma/tratamento farmacológico , Linfoma/tratamento farmacológico , Tumores Neuroectodérmicos Primitivos/tratamento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Barreira Hematoencefálica/efeitos dos fármacos , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Diuréticos Osmóticos/administração & dosagem , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Seguimentos , Germinoma/mortalidade , Germinoma/patologia , Humanos , Lactente , Injeções Intra-Arteriais , Linfoma/mortalidade , Linfoma/patologia , Masculino , Manitol/administração & dosagem , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Tumores Neuroectodérmicos Primitivos/mortalidade , Tumores Neuroectodérmicos Primitivos/patologia , Testes Neuropsicológicos , Taxa de Sobrevida , Resultado do Tratamento
15.
Rehabil Nurs ; 22(3): 143-51; quiz 168, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9171723

RESUMO

This study characterizes the demographic backgrounds of patients in an Israeli geriatric rehabilitation unit, determines the factors associated with their family relationships and the instrumental support they received, and emphasizes the importance of social roles as a personal resource. The study population consisted of 336 low-income Jews, all of whom were immigrants. Virtually all of the subjects had a small, close support network composed mainly of their children and spouses. Their children were the most important source of instrumental support during their hospitalization. The subjects' sources of instrumental support prior to hospitalization varied, depending upon their age, gender, marital status, and social roles. Social exchange theory provided a framework for explaining their social roles. Factors found to be predictors of good family relationships were marital status, living arrangements, instrumental support, social roles, and educational level.


Assuntos
Idoso/estatística & dados numéricos , Enfermagem Geriátrica , Unidades Hospitalares , Reabilitação/enfermagem , Idoso/psicologia , Idoso de 80 Anos ou mais , Feminino , Avaliação Geriátrica , Psiquiatria Geriátrica , Humanos , Israel , Masculino , Pessoa de Meia-Idade , Pesquisa Metodológica em Enfermagem , Apoio Social
16.
Am J Crit Care ; 4(5): 389-96, 1995 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-7489044

RESUMO

BACKGROUND: Although anecdotal data suggest that spouses of aborted sudden cardiac death survivors become enmeshed in the physical and emotional recovery of their mates, few longitudinal studies address the personal struggle of aborted sudden cardiac death survivors and their spouses during recovery. OBJECTIVE: To identify and explore phenomena experienced by aborted sudden cardiac death survivors and their spouses, and to determine implications for care. METHODS: This was a phenomenological study; qualitative interviews were conducted within 3 weeks of aborted sudden cardiac death and continued through 24 weeks after arrest at 6- to 8-week intervals. A total of 180 interviews were conducted with 40 survivors and 30 spouses. Interviews were tape-recorded, transcribed, and analyzed for recurrent themes. RESULTS: For the spouses the point of focus, or reference point, for future decision making was the arrest; for the survivors the reference point was prearrest life. These different reference points led to different concerns between spouses and survivors, from which spousal protectiveness and entrapment emerged. CONCLUSIONS: Acknowledgment of different reference points is essential in planning interventions for aborted sudden cardiac death survivors and their spouses. This population must be encouraged to express their questions, concerns, and fears early. Differences in perspectives should be identified to avoid troubled communication and conflicts.


Assuntos
Adaptação Psicológica , Morte Súbita Cardíaca , Parada Cardíaca/psicologia , Parada Cardíaca/reabilitação , Cônjuges/psicologia , Sobreviventes/psicologia , Atividades Cotidianas , Adulto , Idoso , California , Emoções , Feminino , Humanos , Acontecimentos que Mudam a Vida , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Assunção de Riscos
17.
Rehabil Nurs ; 17(3): 122-5, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1585040

RESUMO

Little is known about the experience of recovery following stroke. A longitudinal, descriptive ethnography formed the basis of the study described in this article, in which 120 interviews were conducted over a period of 6 months with 13 individuals who had experienced lacunar infarcts of the internal capsule of the brain. Participants were interviewed within 72 hours of the infarct and during the acute and rehabilitation phases of recovery. This article discusses the experience of the recovering body and plateaus in this recovery, as well as the phenomena of experimentation with tasks, transformation by familiar surroundings, and sequential focus on involved limbs.


Assuntos
Atividades Cotidianas , Transtornos Cerebrovasculares/psicologia , Qualidade de Vida , Imagem Corporal , Transtornos Cerebrovasculares/enfermagem , Transtornos Cerebrovasculares/reabilitação , Educação Continuada em Enfermagem , Feminino , Serviços de Assistência Domiciliar/normas , Humanos , Pesquisa Metodológica em Enfermagem
18.
J Neurosci Nurs ; 23(4): 207-10, 1991 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-1833478

RESUMO

There have been numerous advances in the neurosciences in the last decade. These include discoveries in the area of neurogenetics, as well as advances in the prevention, diagnosis and treatment of neurologic diseases such as stroke, epilepsy and Parkinson's disease. These advances raise issues which have dramatic implications for nursing. In our society there is an increasing focus on technology. This focus, coupled with the reductionism of cellular and biochemical advances in the neurosciences, tends to take the focus away from the patient. Nursing care is critical in bridging the gap created by technological and biochemical discoveries.


Assuntos
Doenças do Sistema Nervoso/enfermagem , Neurociências/tendências , Educação em Enfermagem/tendências , Genética Médica/tendências , Humanos , Doenças do Sistema Nervoso/genética , Doenças do Sistema Nervoso/terapia , Especialidades de Enfermagem/tendências
19.
J Neurosci Nurs ; 23(4): 235-40, 1991 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-1833483

RESUMO

A longitudinal, clinical ethnography formed the basis of this study. Thirteen stroke survivors, all with lacunar infarcts of the internal capsule of the brain, participated. Survivors were interviewed within 72 hours of the infarct and during acute and rehabilitation phases of recovery. Each was followed for six months, providing a total of 120 interviews. The survivors experienced a paralyzed self secondary to bodily immobility, the shock of the stroke onset and fear of not knowing what might happen next. The terrifying loss of control over bodily movements led to an experiential breakdown. This article chronicles the shock of sudden immobility which left the individuals suspended in a passive, objectified body.


Assuntos
Imagem Corporal , Transtornos Cerebrovasculares/psicologia , Atividades Cotidianas , Adaptação Psicológica , Idoso , Idoso de 80 Anos ou mais , Transtornos Cerebrovasculares/enfermagem , Transtornos Cerebrovasculares/reabilitação , Dependência Psicológica , Feminino , Hospitalização , Humanos , Controle Interno-Externo , Aprendizagem , Masculino , Pessoa de Meia-Idade , Pesquisa Metodológica em Enfermagem , Alta do Paciente , Poder Psicológico
20.
J Neurosci Nurs ; 20(3): 169-73, 1988 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-2968415

RESUMO

Stroke kills more than 175,000 individuals annually and ranks second as a cause of long-term physical disability among Americans. Yet little is known about the experience of recovery in stroke survivors, particularly on a longitudinal basis. Regardless of the distressing impact of stroke on the individual, there is a paucity of literature on the stress of the stroke experience. Critique of recent research in stroke recovery is presented as well as the impact of stroke on the individual. Clinical ethnography as an alternative method of studying stroke recovery is described.


Assuntos
Transtornos Cerebrovasculares/reabilitação , Atividades Cotidianas , Transtornos Cerebrovasculares/fisiopatologia , Transtornos Cerebrovasculares/psicologia , Pessoas com Deficiência/psicologia , Humanos , Qualidade de Vida
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