Cerebral radioprotection by pentobarbital: dose-response characteristics and association with GABA agonist activity

Pentobarbital reduces cerebral radiation toxicity; however, the mechanism of this phenomenon remains unknown. As an anesthetic and depressant of cerebral metabolism, pentobarbital induces its effects on the central nervous system by stimulating the binding of gamma-aminobutyric acid (GABA) to its receptor and by inhibiting postsynaptic excitatory amino acid activity. The purpose of this study is to investigate the role of these actions as well as other aspects of the radioprotective activity of pentobarbital. Fischer 344 rats were separated into multiple groups and underwent two dose-response evaluations. In one set of experiments to examine the relationship of radioprotection to pentobarbital dose, a range of pentobarbital doses (0 to 75 mg/kg) were given intraperitoneally prior to a constant-level radiation dose (70 Gy). In a second series of experiments to determine the dose-response relationship of radiation protection to radiation dose, a range of radiation doses (10 to 90 Gy) were given with a single pentobarbital dose (60 mg/kg intraperitoneally). Further groups of animals were used to evaluate the importance of the timing of pentobarbital administration, the function of the (+) and (-) isomers of pentobarbital, and the role of an alternative GABA agonist (diazepam). In addition, the potential protective effects of alternative methods of anesthesia (ketamine) and induction of cerebral hypometabolism (hypothermia) were examined. Enhancement of survival time from acute radiation injury due to high-dose single-fraction whole-brain irradiation was maximal with 60 mg/kg of pentobarbital, and occurred over the range of all doses examined between 30 to 90 Gy. Protection was seen only in animals that received the pentobarbital before irradiation. Administration of other compounds that enhance GABA binding (Saffan and diazepam) also significantly enhanced survival time. Ketamine and hypothermia were without protective effect. Protection from acute radiation-induced mortality by pentobarbital in the rat model is a reproducible phenomenon and is associated with the GABA agonistic activity of the compound. This property of GABA agonists offers the potential for a novel approach to enhancement of the efficacy of radiation therapy in the treatment of brain tumors.     

Hepatitis B screening in a New York City obstetrics service.

A cross-sectional chart review study was performed of hepatitis B virus (HBV) surface antigen screening of 532 women admitted to a New York City hospital obstetrics service from 1984 to 1985. Comparison of serologic results to risk factors for hepatitis B revealed that women born outside the United States and those with a positive test for or history of a sexually transmitted disease were more likely to be infected with HBV. Obstetric clinics with large immigrant populations should consider screening all patients for HBV.     

N-3-pyridylmethyl-N''-p-nitrophenylurea ocular toxicity in man and rabbits.

Ingestion of the rat poison N-3-pyridylmethyl-N'-p-nitrophenylurea (PNU) produced ocular toxicity in three humans and in an animal model, the Dutch Belted rabbit. The electroretinogram b wave was especially susceptible to the effects of the rodenticide, and the target tissue appeared to be the retinal pigment epithelium. Injection of PNU itself did not produce ocular toxicity. The poison had to be administered orally. Gentamicin administered orally with PNU prevented the ocular toxicity. Presumably this antibiotic killed those gastrointestinal bacteria responsible for PNU's metabolism into an ocular toxin. L-tryptophan, a known antidote for the lethal effects of PNU, was an antidote for the ocular toxicity when administered orally but not when administered parenterally.     

Leukemia,lymphoma, and multiple myeloma following selected medical conditions

The role of selected prior medical conditions in the etiology of hematopoietic malignancies was examined in a case-control study of members of two regional branches of the Kaiser Permanente Medical Care Program (USA). Past history of chronic infectious, autoimmune, allergic, and musculoskeletal disorders was abstracted from medical records for leukemia (n = 299), non-Hodgkin's lymphoma (NHL, n = 100), and multiple myeloma (n = 175) cases and matched controls (n = 787). Little difference was found between cases and controls for most of the chronic conditions evaluated, including sinusitis, carbuncles, urinary tract infections, pelvic infections, herpes zoster, asthma, rheumatoid arthritis, psoriasis, bursitis, and gout. Only three statistically significant elevated risks were found, i.e., with combined disc disease myeloma among patients with prior eczema and disk and other musculoskeletal conditions, and NHL following tuberculosis. Only two of these associations showed consistent patterns by sex and geographic region (myeloma with eczema and with musculoskeletal conditions). While prior history of eczema and musculoskeletal conditions may slightly increase risk of myeloma, this study provided little if any support for an association of chronic infectious, autoimmune, allergic, and musculoskeletal conditions with subsequent occurrence of the leukemias or NHL. Additionally, these data did not support a role for chronic antigenic stimulation, as defined in previous epidemiologic studies, in the etiology of hematopoietic malignancies.Ms Doody and Drs Linet, Pottern, Boice, and Fraumeni are with the Epidemiology and Biostatistics Program, National Cancer Institute. Dr Glass is with the Kaiser Permanente Medical Care Program, Northwest Region, Portland, Oregon, USA. Dr Friedman is with the Kaiser Permanente Medical Care Program, Northern California Region, Oakland, California, USA. Address correspondence to Ms Doody, Radiation Epidemiology Branch, National Cancer Institute, Executive Plaza North, Room 408, Bethesda, MD 20892, USA. This research was supported in part by National Cancer Institute contracts NO1-CP-01047, NO1-CP-01054, NO1-CP-11009, NO1-CP-11037, NO1-CP-31035, and NO1-CP-61006.     

Tumors of the central nervous system. Improvement in outcome through a multimodality approach

More children with CNS tumors will continue to be cured of their neoplasms as a result of improved surgical, radiotherapeutic, and chemotherapeutic intervention. The complex problems seen in these patients mandate their treatment at academic centers actively involved in therapeutic investigations and capable of providing comprehensive multidisciplinary care.     

Retention of "safe" blood donors. The Retrovirus Epidemiology Donor Study

BACKGROUND: There are obvious advantages to increasing donor retention. However, for reasons of blood safety, certain donors may, in fact, be more desirable to retain than others. “Safe” donors are defined as those who provided a blood donation that was negative on all laboratory screening tests and who subsequently reported no behavioral risks in response to an anonymous survey. This study identifies the most important factors affecting the intention of “safe” donors to provide another donation. STUDY DESIGN AND METHODS: An anonymous survey asking about donation history, sexual history, injecting drug use, and recent donation experience was mailed to 50,162 randomly selected allogeneic donors (including directed donors) who gave blood from April through July or from October through December 1993 at one of the five United States blood centers participating in the Retrovirus Epidemiology Donor Study. Before mailing, questionnaires were coded to designate donors with nonreactive laboratory screening tests at their most recent donation. RESULTS: A total of 34,726 donors (69%) responded, with substantially higher response among repeat donors. According to reported intentions only, the vast majority of “safe” donors indicated a high likelihood of donating again within the next 12 months. Only 3.4 percent reported a low likelihood of donating again. A comparison of those likely to return and those unlikely to return reveals significant differences in demographics and in ratings of the donation experience. A higher proportion of those unlikely to return were first-time donors, minority-group donors, and donors with less education. The highest projected loss among “safe” donors was seen for those who gave a fair to poor assessment of their treatment by blood center staff or of their physical well-being during or after donating. CONCLUSION: These data suggest that efforts to improve donors' perceptions of their donation experience, as well as attention to the physical effects of blood donation, may aid in the retention of both repeat and first-time donors.     

Quantitative MRI studies for assessment of multiple sclerosis.

Although magnetic resonance imaging (MRI) is a valuable aid in the initial diagnosis of multiple sclerosis (MS), quantitatively MRI has been disappointing in staging and evaluating therapy protocols by means of serial examinations. In this study, image processing algorithms were developed for the global analysis of MR images of the cerebrum. Limited three-dimensional segmentation was achieved through histogram analysis by these algorithms, which are essentially operator independent. The effects of coil response and tip angles, patient positioning, and interslice gap thicknesses were examined for 10 MS patients with repeated examinations for a total of 72 images. Effects of technique and instrumentation errors were approximately 6%, and agreement between two independent operators for measuring the total MR pixel sum from periventricular effusions and intense MS plaques was better than 97% with a standard deviation of 2.9%.     

Bilateral transpedicular decompression and Harrington rod stabilization in the management of severe thoracolumbar burst fractures.

Fifty-eight patients with severe thoracolumbar burst fractures were treated with bilateral transpedicular decompression, Harrington rod instrumentation, and spine fusion. Spinal realignment and stabilization was achieved by contoured dual Harrington distraction rods supplemented by segmental sublaminal wiring. Posterior element fractures were noted in 25 patients, 9 of whom had associated dural tears. Computed tomography was performed to assess the cross-sectional area of the spinal canal before surgery and after decompression. Patients at initial evaluation averaged greater than 67% spinal canal compromise. After surgery, successful decompression was accomplished in 57 patients. One patient required staged, anterior thoracoabdominal decompression and fibula strut grafting. At follow-up (average, 43 months; range, 25-70 months), neurologic improvement was found in 77% of the patients who initially presented with neurologic deficits. Thirty-four of 40 patients with incomplete paraplegia improved one or more subgroups on the Frankel scale. A solid fusion was attained in all 58 patients. No patient had a significant residual kyphotic deformity. Single-stage bilateral transpedicular decompression and dual Harrington rod instrumentation reliably provides decompression of the spinal canal and restores spinal alignment. The procedure allows early mobilization and provides an environment for solid fusion and maximum neurologic return.