摘要:

OBJECTIVE:To review the principles of and the experimental and clinical results of gene therapy for cerebrovascular disease.METHODS:Literature review.RESULTS:Vectors for gene transfer into the brain or into the cerebral vasculature include naked plasmid deoxyribonucleic acid, cationic liposomes, and viruses such as adenovirus, retrovirus, adeno-associated virus, and herpes simplex virus. Experiments using these vectors showed that intra- or perivascular application to systemic arteries can lead to transfection and expression of a foreign transgene in the adventitia and the endothelium. Intrathecal administration can lead to transfection and foreign transgene expression in leptomeningeal cells as well as in fibroblasts of blood vessel adventitia. Biological effects demonstrated thus far include increased nitric oxide production by transfection of cerebral arterial adventitia with adenovirus expressing nitric oxide synthase. Adenovirus carrying foreign genes have been used to decrease neuronal damage in cerebral ischemia and to decrease blood pressure in spontaneously hypertensive rats. Vectors and therapeutic applications for gene therapy are evolving rapidly.CONCLUSION:Gene therapy for cerebrovascular disease is likely to have clinical application in the near future and will have a major impact on neurosurgery. Neurosurgeons will need to be aware of the literature in this area.

ISSN:0148-396X    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0148-396X    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

OBJECTIVE:Prolactinomas are frequently treated primarily with dopamine agonists; however, these agents have disadvantages and require life-long therapy. We therefore reassessed transsphenoidal microsurgery as an alternative therapy.METHODS:We reviewed the data for 121 female patients treated surgically for prolactinomas between 1976 and 1979 (Group 1) and 98 patients treated between 1988 and 1992 (Group 2).RESULTS:Of 219 women, 92% with preoperative prolactin (PRL) values of ≤100 ng/ml and 91% with intrasellar microadenomas experienced initial remission; 80 to 88% of patients with intrasellar macroadenomas or macroadenomas showing moderate suprasellar extension or focal sphenoid sinus invasion experienced remission. Women with PRL values of >200 ng/ml and those with larger and more invasive adenomas experienced poorer outcomes (37-41% remission). Lower preoperative PRL values and adenoma stage were the best predictors of initial surgical outcomes. At the most recent evaluations, 89% of women who experienced initial remission continued to experience clinical remission; 85% exhibited normal PRL values, and 5% demonstrated mild, asymptomatic, recurrent hyperprolactinemia (PRL values of <34 ng/ml). In Group 1, 84% of patients continued to experience remission (82% with normal PRL values) after a median follow-up period of 15.6 years. In Group 2, 97% of patients continued to experience remission (88% with normal PRL values) after a median follow-up period of 3.2 years. Lower postoperative PRL values were the best predictors of long-term remission.CONCLUSION:Transsphenoidal microsurgery is an effective alternative to long-term medical therapy for selected patients with prolactinomas. Successful outcomes and long-term remission were achieved in patients with microadenomas and noninvasive macroadenomas.

ISSN:0148-396X    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0148-396X    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0148-396X    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0148-396X    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

OBJECTIVE:Although intramedullary spinal cord ependymomas are amenable to surgical total resection, some ependymomas have been associated with severe surgical morbidity. The aim of this study is to determine what factors affect surgical morbidity.METHODS:Thirty-six consecutive patients who underwent surgical removal of an intramedullary spinal cord ependymoma between September 1980 and June 1998 were studied retrospectively. This series includes 19 women and 17 men between the age of 12 and 67 years (mean age, 41.2 yr). The location of the tumors was cervical in 24 cases, cervicothoracic in 3 cases, thoracic in 7 cases, and conus in 2 cases. At surgery, complete removal was achieved in 34 patients and subtotal removal was performed in the remaining 2.RESULTS:There has been no tumor recurrence in any patient except one who had an anaplastic ependymoma after a mean follow-up period of 56 months. The surgery improved neurological status in 14 of the 36 patients (39%). However, five patients (14%) experienced persistent deteriorations in clinical grade caused by surgery. Four of the five patients harbored benign ependymomas in the thoracic cord and characteristically demonstrated arachnoid scarring and cord atrophy at surgery, indicating that tumors had been present for a long time.CONCLUSION:Surgical removal of intramedullary ependymomas is beneficial to patients. However, the thoracic cord may be susceptible to surgical manipulations for intramedullary ependymomas. In addition, intraoperative findings of arachnoid scarring and cord atrophy are ominous for surgical morbidity.

ISSN:0148-396X    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0148-396X    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

OBJECTIVE:Animal and human studies have shown increased delivery of radiolabeled compounds across the blood-brain-tumor barrier using intra-arterial (IA) Cereport (RMP-7; Alkermes Inc., Cambridge, MA) with a radiolabeled tracer. This present study assesses the safety, tolerance, and preliminary efficacy of the IA administration of carboplatin with Cereport.METHODS:An open-label dose escalation study of IA Cereport (10-300 ng/kg) with 100 mg of IA carboplatin was conducted in 11 patients with recurrent malignant gliomas and 1 patient treated adjuvantly after radiation therapy. Tumor size and laboratory and clinical statuses were assessed.RESULTS:Adverse events were mainly neurological in nature and corresponded to the anatomic location of the tumor. Karnofsky performance scale scores did not decline, overall, for those patients who had tumor response. Tumor shrinkage was observed in three of six evaluable patients who received a dose of 300 ng/kg with durable responses of 60, 64, and 106+ weeks.CONCLUSION:Previous studies have demonstrated increased permeability in human gliomas using IA Cereport. This study demonstrates durable imaging responses using 100 mg of IA carboplatin in combination with Cereport. The drug combination in this patient population seems to be safe and acceptable, providing a novel means of antitumor dose intensification.

ISSN:0148-396X    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0148-396X    

出版商:OVID    

年代:1999

数据来源: OVID