James M. Schuster

SURVIVAL AT 5 YEARS OF A COHORT OF NEWBORN INFANTS WITH MYELOMENINGOCELE

Over a nine‐year period, 63 viable newborns with myelomeningocele were consecutively treated, of whom 11 (17%) developed brainstem symptoms assessed to be potentially life‐threatening. All 11 underwent brainstem decompression by cervical laminectomy with stent placement between the fourth ventricle and the spinal subarachnoid space, at a median âge of 8 months. 86% survived to 60 months of age. Those with brainstem dysfunction had a significantly greater mortality than those without, despite aggressive neurosurgical management by brainstem decompression.

Hyperthermic modulation of radiolabelled antibody uptake in a human glioma xenograft and normal tissues

These experiments investigate the biodistribution of radiolabelled MAb in a human glioma xenograft model after 4 h of local hyperthermia (HT) with a twofold purpose: to maximize the ratio of cumulative isotope activity in tumour relative to normal tissues, and to examine the temperature dependence of the effect. Restrained, unanaesthetized athymic nude mice bearing 150-200 mm3 s.c. human glioma xenografts (D-54 MG) were given 5 micrograms 125I-labelled specific and 131I-labelled non-specific MAb immediately prior to HT (water bath) for 4 h. Cohorts of five animals were killed at 0, 4, 8, 12 and 24 h after HT, and normal and tumour tissues were analysed for activity of each isotope. MAb uptake in tumour was greater with HT than with controls, and greater for specific MAb than for non-specific MAb. Uptake in thyroid was not significantly affected by tumour HT, suggesting that HT does not increase the rate of dehalogenation. Uptake in several other normal tissues away from the heated site was significantly increased (as were reported previously in mice anaesthetized with pentobarbital sodium during treatment; Cope et al. 1990), but the temporal pattern was different from that observed in tumour, suggesting that short-lived isotopes might lead to preferential dose deposition in heated tumour. Doses to various tissues were calculated for isotopes having a range of half-lives; the results clearly indicated that maximum differential in uptake between tumour and normal tissues would occur for isotopes with half-lives < 3 days. A separate series of experiments compared tumour uptake for 40, 42 and 44 degrees C HT. These results demonstrated that 42 and 44 degrees C HT created maximum enhancement in specific antibody uptake over controls. Specific MAb was retained over time in 42 degrees C-heated tumours, whereas significant washout occurred for non-specific MAb, which indicates that MAb retention was due to increased specific binding at this temperature and not vascular damage with antibody trapping. Retention of both specific and non-specific MAb was seen at 44 degrees C, suggesting that vascular damage becomes an important non-specific mechanism for antibody retention at higher temperatures.

BAEPs IN INFANTS WITH MYELOMENINGOCELE AND LATER DEVELOPMENT OF CHIARI II MALFORMATION‐RELATED BRAINSTEM DYSFUNCTION

Thirty‐seven infants with myelomeningocele received brainstem auditory evoked potentials (BAEPs) at a median age of eight days. No infant had brainstem dysfunction at the time of testing. Median follow‐up was at 30 months. Of 12 infants who subsequently developed brainstem dysfunction at a median age of three months, 11 had had abnormal neonatal BAEPs. In contrast, only 10 of 25 infants who did not develop brainstem dysfunction had abnormal BAEPs. The mean average I‐V interpeak latencies was greater among those who developed symptoms than among those who did not. Neonatal BAEPs can identify a group of asymptomatic infants with myelomeningocele who need close follow‐up for the subsequent development of brainstem dysfunction.

Two Approaches for Enhancing Radioimmunotherapy: ∝ Emitters and Hyperthermia

The lack of specificity of chemotherapy and external beam radiation frequently results in toxicity to normal organs, limiting doses to below those at which tumor control would be reached. Because of its potential for increasing the specificity of cytotoxic effects, radioimmunotherapy is a conceptually appealing approach for cancer treatment. Assuming that an antibody can be generated that is specific for the cancer in question, then combining this antibody with an appropriate radionuclide should yield a treatment modality with a high therapeutic index. Unfortunately, with the exception of highly radiosensitive tumors (Eary et al. 1990), results from most clinical trials indicate that the promise of antibody-mediated radiotherapy has not been realized. The lack of efficacy for radioimmunotherapy is not surprising since only a small fraction of labeled antibody has been reported to localize in tumor following intravenous administration (generally between 0.001% and 0.01% injected dose per gram), and significant accumulation in normal tissues also has been observed (Carrasquillo 1989; Zalutsky et al. 1990).