Alterations in cerebrospinal fluid uridine,hypoxanthine, and xanthine in head-injured patients

1. Examination of the cerebrospinal fluid (CSF) of head-injured patients reveals that the concentration of intraventricular xanthine is elevated and that of uridine is decreased relative to those of adult lumbar CSF. 2. No correlations were observed between CSF lactate and CSF hypoxanthine, xanthine, or uridine, suggesting that changes in purine metabolites and the pyrimidine nucleoside do not index similar cellular events as does lactic acid production. 3. Ventricular CSF from hydrocephalic infants had uridine and hypoxanthine concentrations not significantly different from those of normal adult lumbar CSF, but xanthine was significantly elevated. 4. Since uridine has anticonvulsant properties and is a crucial substrate for cerebral metabolism, it may be useful to evaluate this pyrimidine for use in the management of patients with head injury.     

Antibody responses to galectin-8, TARP and TRAP1 in prostate cancer patients treated with a GM-CSF-secreting cellular immunotherapy

A critical factor in clinical development of cancer immunotherapies is the identification of tumor-associated antigens that may be related to immunotherapy potency. In this study, protein microarrays containing >8,000 human proteins were screened with serum from prostate cancer patients (N = 13) before and after treatment with a granulocyte–macrophage colony-stimulating factor (GM-CSF)-secreting whole cell immunotherapy. Thirty-three proteins were identified that displayed significantly elevated (P ≤ 0.05) signals in post-treatment samples, including three proteins that have previously been associated with prostate carcinogenesis, galectin-8, T-cell alternative reading frame protein (TARP) and TNF-receptor-associated protein 1 (TRAP1). Expanded analysis of antibody induction in metastatic, castration-resistant prostate cancer (mCRPC) patients (N = 92) from two phase 1/2 trials of prostate cancer immunotherapy, G-9803 and G-0010, indicated a significant (P = 0.03) association of TARP antibody induction and median survival time (MST). Antibody induction to TARP was also significantly correlated (P = 0.036) with an increase in prostate-specific antigen doubling time (PSADT) in patients with a biochemical (PSA) recurrence following prostatectomy or radiation therapy (N = 19) from in a previous phase 1/2 trial of prostate cancer immunotherapy, G-9802. RNA and protein encoding TARP and TRAP1 was up-regulated in prostate cancer tissue compared to matched normal controls. These preliminary findings suggest that antibody induction to TARP may represent a possible biomarker for treatment response to GM-CSF secreting cellular immunotherapy in prostate cancer patients and demonstrates the utility of using protein microarrays for the high-throughput screening of patient-derived antibody responses.     

EXO5-DNA structure and BLM interactions direct DNA resection critical for ATR-dependent replication restart

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Burn Injury Reduces Neutrophil Directional Migration Speed in Microfluidic Devices

Thermal injury triggers a fulminant inflammatory cascade that heralds shock, end-organ failure, and ultimately sepsis and death. Emerging evidence points to a critical role for the innate immune system, and several studies had documented concurrent impairment in neutrophil chemotaxis with these post-burn inflammatory changes. While a few studies suggest that a link between neutrophil motility and patient mortality might exist, so far, cumbersome assays have prohibited exploration of the prognostic and diagnostic significance of chemotaxis after burn injury. To address this need, we developed a microfluidic device that is simple to operate and allows for precise and robust measurements of chemotaxis speed and persistence characteristics at single-cell resolution. Using this assay, we established a reference set of migration speed values for neutrophils from healthy subjects. Comparisons with samples from burn patients revealed impaired directional migration speed starting as early as 24 hours after burn injury, reaching a minimum at 72–120 hours, correlated to the size of the burn injury and potentially serving as an early indicator for concurrent infections. Further characterization of neutrophil chemotaxis using this new assay may have important diagnostic implications not only for burn patients but also for patients afflicted by other diseases that compromise neutrophil functions.     

Is group progressive relaxation training as effective with hyperactive children as individual EMG biofeedback treatment?

This study examined whether group progressive relaxation training was as effective as individual EMG biofeedback training in facilitating the academic achievement and self-control of 45 hyperactive elementary school children. Academic achievement was assessed with the Gates-MacGinities Reading Tests, and self-control was measured with the Nowicki-Strickland and the Teacher Rating scales. Eight sessions were scheduled at weekly intervals. Progressive relaxation was conducted in groups of seven or eight and was induced with a commercial audiocassette program. EMG training augmented frontalis biofeedback with those taped exercises. A placebo group listened to taped children's stories. Multivariate analysis of variance indicated no significant differences among the three contrast groups when all dependent variables were considered together. However, univariate F values and discriminant analysis disclosed locus of control to be significantly more internal for the progressive relaxation condition. Also, differences between the two relaxation and the placebo groups, though not statistically significant, were all in the expected direction. While the relative efficacy of group progressive relaxation could not be established conclusively, the data appeared sufficiently positive to warrant further investigation of this cost-effective prospective intervention.The opinions expressed by the authors are not necessarily those of their respective institutions.     

Rock-Climbing Injuries in Yosemite National Park

This study was presented in part at the annual meeting of the Wilderness Medical Society at Aspen, Colorado, in August 1986 and at “Mountain Medicine 1987,” Leavenworth, Washington, in November 1987.We questioned 220 injured rock climbers or their partners seen consecutively at the Yosemite (California) Medical Clinic over 3 ½ years regarding details of their accidents. Injury type and location were extracted from medical records and severity quantified. The National Park Service rescued 27% of the climbers. Injured climbers were characteristically male (88%) and experienced (mean 5.9 years) and typically fell while leading climbs (66%). Among 451 injuries, 50% were to the skin or subcutaneous tissues, while 28% involved the lower extremity and were predominantly fractures. In terms of each climber''s most severe injury (n = 220), 45% involved the lower extremities (30% from the ankle alone). Head injury or hypothermia caused 12 of 13 fatalities, showing the lowest case-fatality rate reported to date among injured climbers (6%). Rescue personnel successfully managed airways in victims of head injuries, anticipated and treated complications of hypothermia, and stabilized fractures. Victims requiring immediate extensive surgical intervention or blood transfusion usually died before rescue could be effected.