Tumor necrosis factor (TNF) activity was inhibited during the development of actively-induced, chronic relapsing experimental allergic encephalomyelitis (CREAE) in Biozzi AB/H mice, using a mouse TNF-specific (TN3.19.12) antibody and bivalent human p55 and p75 TNF receptor-immunoglobulin (TNFR-Ig) fusion proteins. The development of disease could be inhibited when repeated doses of antibody were administered prior to the anticipated onset. It has now also been shown that a therapeutic effect is evident even when antibody is administered after the onset of clinical signs, further indicating an important role for TNF in pathogenic effector mechanisms in CREAE. Although biologically-active TNF was not detected in the circulation, TNF-alpha was detected in lesions within the central nervous system (CNS). This suggested that the CNS may be the main site for TNF-specific immunomodulation and was supported by the observation that intracranial injection was significantly more potent than that administered systemically, for both antibody and TNFR-Ig fusion proteins. The fusion proteins were as effective as antibody at doses 10-100-fold lower than that used for antibody, reflecting their higher neutralizing capacity in vitro. Although treatment was not curative and relapse inevitably occurred in this model if treatment was not sustained, the data indicate that anti-TNF immunotherapy, especially within the CNS, can inhibit CREAE and may, therefore, be useful in the control of human neuroimmunological diseases.

Animals↗

PubMed1994

Pediatric astrocytomas. The Louisville experience: 1978-1988.

PURPOSE: The purpose of this study is to retrospectively analyze all pediatric patients with the diagnosis of astrocytoma treated either definitively or postoperatively in our department from 1978 through 1988. Grade, age, T-stage, tumor location, and extent of resection are individually analyzed as prognostic indicators of overall survival. MATERIALS AND METHODS: Pediatric astrocytoma patients (grades I-IV) diagnosed by CT-guided biopsy or surgical resection were assessed. Patients were treated with external beam radiotherapy to involved fields using 4- or 6-MV photons. Daily doses ranged from 1.5 to 2.0 Gy; total doses from 41.4 to 66 Gy. Treatment was given to 17 patients (9 male, 8 female), aged 18 years and younger: 11 patients had low-grade (I & II) astrocytoma with incomplete margins; 3 patients had anaplastic astrocytoma; and 3 patients had glioblastoma multiforme. RESULTS: Overall survival at 140 months was 63%. Median follow-up of patients living NED was 69 months, with a range of 39-140 months. Nine of the eleven (82%) low-grade patients survived NED; 1 of 3 anaplastic patients is NED at 44 months follow-up; 1 died of intercurrent disease at 80 months; the third died of disease at 49 months. All three glioblastomas succumbed to local disease at 9, 15, and 27 months from diagnosis. Univariate analysis showed only grade to be prognostically significant (p < .03) in determining overall survival. CONCLUSION: Postoperative radiotherapy for unresected or partially resected low-grade astrocytomas produces excellent local control. Higher grade astrocytomas require further investigational studies to improve survival and local control. Grade is prognostically significant with respect to overall survival.

Adolescent↗

PubMed1994

High-dose methylprednisolone after acute spinal cord injury.

The spinal cord-injured patient has presented a dilemma for nursing care since the earliest survivor of such an injury. Recent research has identified a means of improving neurologic recovery for these patients. Proper administration of high-dose MP within 8 hours after injury provides the patient with the best potential for improvement. Ensuring immobilization and prevention of the complications of immobility are the next most significant actions the nurse can undertake to assist such a patient through a devastating injury toward optimal functional outcome. With continued research and education of caregivers, the residual effects of spinal cord injury may be further abated.

Drug Administration Schedule↗