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:

OBJECTIVEIn an effort to increase the effect of intrathecal baclofen on upper-extremity spasticity, the tip of the intrathecal catheter was placed at the T6–T7 level rather than at the traditional T11–T12 level in children with spastic quadriparesis.METHODSTwelve children with spastic quadriparesis from varying causes had significant reductions in spasticity after a test dose of intrathecal baclofen and subsequently underwent placement of a programmable pump and intrathecal catheter tip placed at the T6–T7 level with fluoroscopic guidance. With the use of Ashworth scores for four muscle groups in both the upper and lower extremities, degrees of spasticity were determined by a physiatrist preoperatively and at 1, 3, 6, and 12 months postoperatively. Mean changes in upper- and lower-extremity Ashworth scores and baclofen dosages for the entire cohort were compared with published results in which the catheter tip had been placed at the T11–T12 level.RESULTSSpasticity was significantly reduced in all muscle groups (P< 0.001). The lower-extremity reduction in spasticity of 1.6 points at 3 and 12 months was greater than published reductions of 1.1 points at 3 and 12 months. The upper-extremity reduction in spasticity was noticeably greater at 3 and 12 months (1.7 and 2.0 points, respectively) than published results at 3 and 12 months (0.4 and 0.6 points, respectively). At 3, 6, and 12 months, our mean baclofen dosage remained below the dosages administered at the T11–T12 level. There were no complications related either to the positioning of the catheter higher in the spinal canal or to the administration of baclofen at the T6–T7 level.CONCLUSIONCompared with published results, placement of the tip of the intrathecal catheter at the T6–T7 level was associated with greater relief of upper-extremity spasticity without loss of effect on the lower extremities. The mean dosages of baclofen in our study group were lower compared with mean dosages administered at the T11–T12 level. There was no morbidity related to the more rostral location of the catheter.

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

ISSN:0148-396X    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

OBJECTThe current prognosis for patients with malignant brain tumors remains poor, and new therapeutic options are urgently needed. We previously have shown that prolongation of survival can be achieved in C57BL/6 mice (H-2b) with a syngeneic intracerebral or subcutaneous glioma when treated with allogeneic mouse fibroblasts (H-2k) genetically engineered to secrete interleukin-2 (IL-2). Like other antigens, tumor-associated antigens are recognized by cytotoxic T lymphocytes in the context of determinants specified by the major histocompatibility complex class I locus. Because the rejection of allogeneic major histocompatibility complex determinants has the property of an immune adjuvant, immunotherapy of glioma with a cellular immunogen that combines the expression of both syngeneic class I determinants and allogeneic antigens could have advantages over an immunogen that expresses syngeneic or allogeneic determinants alone.METHODSTo investigate this question in a mouse glioma model, we further modified allogeneic mouse fibroblasts (H-2k), not only for IL-2 secretion, but also for the expression of H-2Kbclass I determinants. We tested the immunotherapeutic properties of these semiallogeneic cells (LM-IL-2/H-2Kb) in C57BL/6 mice with Gl261 glioma in both subcutaneous and intracerebral glioma models.RESULTSC57BL/6 mice with either a subcutaneous or intracerebral glioma treated solely by injection of these IL-2-secreting semiallogeneic cells had significantly prolonged survival rates compared with untreated mice or mice treated with cells secreting only IL-2 or cells lacking the H-2Kbdeterminants. In some instances, the mice treated with the semiallogeneic cells survived indefinitely, suggesting total eradication of the glioma. When a51Cr release assay was used, the specific immunocytotoxicity measured by release of isotopes from labeled Gl261 glioma cells coincubated with spleen cells from mice immunized with the semiallogeneic IL-2-secreting cells was significantly higher than that of spleen cells from nonimmunized mice or mice immunized with allogeneic cells lacking syngeneic major histocompatibility complex determinants. In addition, antibody depletion studies using monoclonal antibodies against CD8+and natural killer/lymphokine-activated killer cells demonstrated a specific CD8+immunocytotoxic response in animals immunized with the semiallogeneic IL-2-secreting cells compared with only a natural killer/lymphokine-activated killer response in mice immunized with the allogeneic IL-2-secreting cells.CONCLUSIONThe augmented immune response against glioma in mice treated with the semiallogeneic IL-2-secreting cells points toward a new form of immunotherapy, “immuno-gene therapy,” for patients with malignant intracerebral glioma.

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