Time-frequency balanced spectral entropy as a measure of anesthetic drug effect in central nervous system during sevoflurane, propofol, and thiopental anesthesia

BACKGROUND: Time-frequency balanced spectral entropy of electroencephalogram (EEG) and frontal electromyogram (FEMG) is a novel measure of hypnosis during anesthesia. Two Entropy parameters are described: Response entropy (RE) is calculated from EEG and FEMG; and State Entropy (SE) is calculated mainly from EEG. This study was performed to validate their performance during transition from consciousness to unconsciousness under different anesthetic agents. METHODS: Response entropy, SE [S/5 Entropy Module, M-ENTROPY (later in text: Entropy), Datex-Ohmeda Division, Instrumentarium Corp., Helsinki, Finland] and BIS (BIS XP, A-2000, Aspect Medical Systems, Newton, MA) data were collected from 70 patients; 30 anesthetized with propofol 2 mg kg-1, 20 with sevoflurane inhalation, and 20 with thiopental 5 mg kg-1. Loss and regaining of consciousness (LOC, ROC) was tested every 10 s, and sensitivity, specificity, and prediction probability (Pk) were calculated. Behavior of the indices was studied. RESULTS: Sensitivity, specificity, and Pk values for consciousness were high and similar for all indices. During regaining of consciousness after propofol bolus, RE, SE, and BIS values recovered by 81 +/- 22%, 75 +/- 26%, and 59 +/- 18% (mean +/- SD), respectively, from the minimum relative to their baseline. After thiopental bolus, RE, SE, and BIS values recovered by 86+/-21%, 88 +/- 13%, and 63 +/- 14%, respectively. The relative rise was higher in RE and SE compared with BIS (P < 0.01). During deep levels of hypnosis, RE and SE decreased monotonously as a function of burst suppression ratio, while BIS showed biphasic behavior. On average, RE indicated emergence from anesthesia 11 s earlier than SE, and 12.4 s earlier than BIS. CONCLUSIONS: All indices, RE, SE, and BIS, distinguished excellently between conscious and unconscious states during propofol, sevoflurane, and thiopental anesthesia. During burst suppression, Entropy parameters RE and SE, but not BIS, behave monotonously. During regaining of consciousness after a thiopental or propofol bolus, RE and SE values recovered significantly closer to their baseline values than did BIS. Response entropy indicates emergence from anesthesia earlier than SE or BIS.     

Phase I trial of temozolomide plus O6-benzylguanine for patients with recurrent or progressive malignant glioma.

PURPOSE: We conducted a two-phase clinical trial in patients with progressive malignant glioma (MG). The first phase of this trial was designed to determine the dose of O6-BG effective in producing complete depletion of tumor AGT activity for 48 hours. The second phase of the trial was designed to define the maximum tolerated dose (MTD) of a single dose of temozolomide when combined with O6-BG. In addition, plasma concentrations of O6-BG and O6-benzyl-8-oxoguanine were evaluated after O6-BG. PATIENTS AND METHODS: For our first phase of the clinical trial, patients were scheduled to undergo craniotomy for AGT determination after receiving a 1-hour O6-BG infusion at 120 mg/m2 followed by a continuous infusion at an initial dose of 30 mg/m2/d for 48 hours. The dose of the continuous infusion of O6-BG escalated until tumor AGT was depleted. Once the O6-BG dose was established a separate group of patients was enrolled in the second phase of clinical trial, in which temozolomide, administered as a single dose at the end of the 1-hour O6-BG infusion, was escalated until the MTD was determined. RESULTS: The O6-BG dose found to be effective in depleting tumor AGT activity at 48 hours was an IV bolus of 120 mg/m2 over 1 hour followed by a continuous infusion of 30 mg/m2/d for 48 hours. On enrolling 38 patients in six dose levels of temozolomide, the MTD was established at 472 mg/m2 with dose-limiting toxicities limited to myelosuppression. CONCLUSION: This study provides the foundation for a phase II trial of O6-BG plus temozolomide in temozolomide-resistant MG.     

Syndecan-1 expression during postnatal tooth and oral mucosa development in rats aged from two days to six weeks

Syndecans are a family of heparan sulphate proteoglycans that regulate cell-matrix interactions that influence cell growth, proliferation and morphology. The aim of this study was to observe changes in the expression of Syndecan-1 in the developing epithelium of the rat oral mucosa and in the epithelial cell rests of Malassez in the developing periodontium of normal rat molars, from late crown development through to early eruption. Immuno-histochemistry (Syndecan-1 N-18) and histochemistry (Alcec Bluel were used to observe changes in the expression of Syndecon-1 in rats aged two to 42 days. Results indicated that during normal tooth development in the rat, labelling or staining of variable intensity for Syndecan-1 was demonstrated in the stratified oral epithelium above the stratum basale in the rat tongue and palate, and in ameloblasts of the developing molar in rats aged two to 14 days. Histochemical staining of the predentine and dentine layers was consistent in all specimens. Labelling or staining for Syndecan-1 was negative in the rat periodontal ligament, which may suggest that either Syndecan-1 was not expressed during normal molar root development or that continued work is required for identification of a suitable label in rats.     

Viruses in the treatment of brain tumors

The grave outlook for malignant glioma patients in spite of improvements to current modalities has ushered in new approaches to therapy. Viruses have emerged on the scene and gained attention for their ability to play essentially two roles: first, as vectors for therapeutic gene delivery and second, as engineered infectious agents capable of selectively lysing tumor cells. To date, clinical brain tumor trials using viruses for gene delivery have employed retroviral or adenoviral vectors to introduce ganciclovir susceptibility to tumors in the form of the HSV1-TK gene. Clinical oncolytic studies, on the other hand, have evaluated a conditionally replicating HSV as an antineoplastic agent. Despite some promise afforded by these trials, further studies are warranted; the investigation of additional viruses to play these roles is inevitable and is now precedented.     

Persistent protective effect of heat-killed Escherichia coli producing "engineered," recombinant peanut proteins in a murine model of peanut allergy

BACKGROUND: Peanut allergy (PNA) is a life-threatening food allergy for which there is no definitive treatment. OBJECTIVE: We investigated the long-term immunomodulatory effect of heat-killed Escherichia coli producing engineered (mutated) Ara h1, 2, and 3 (HKE-MP123) administered rectally (pr) in a murine model of PNA. METHODS: Peanut-allergic C3H/HeJ mice received 0.9 (low dose), 9 (medium dose), or 90 (high dose) microg HKE-MP123 pr, HKE-containing vector (HKE-V) alone, or vehicle alone (sham) weekly for 3 weeks. Mice were challenged 2 weeks later. A second and third challenge were performed at 4-week intervals. RESULTS: After the first challenge, all 3 HKE-MP123 and HKE-V-treated groups exhibited reduced symptom scores (P <.01,.01,.05,.05, respectively) compared with the sham-treated group. Interestingly, only the medium- and high-dose HKE-MP123-treated mice remained protected for up to 10 weeks after treatment accompanied by a significant reduction of plasma histamine levels compared with sham-treated mice (P <.05 and.01, respectively). IgE levels were significantly lower in all HKE-MP123-treated groups (P <.001), being most reduced in the high-dose HKE-MP123-treated group at the time of each challenge. IL-4, IL-13, IL-5, and IL-10 production by splenocytes of high-dose HKE-MP123-treated mice were significantly decreased (P <.01;.001,.001, and.001, respectively), and IFN-gamma and TGF-beta production were significantly increased (P <.001 and.01, respectively) compared with sham-treated mice at the time of the last challenge. CONCLUSIONS: Treatment with pr HKE-MP123 can induce long-term "downregulation" of peanut hypersensitivity, which might be secondary to decreased antigen-specific T(H)2 and increased T(H)1 and T regulatory cytokine production.     

Widespread arsenic contamination of soils in residential areas and public spaces: an emerging regulatory or medical crisis?

A critical review finds government agencies allow, permit, license, or ignore arsenic releases to surface soils. Release rates are controlled or evaluated using risk-based soil contaminant numerical limits employing standardized risk algorithms, chemical-specific and default input values. United States arsenic residential soil limits, approximately 0.4- approximately 40 ppm, generally correspond to a one-in-one-million to a one-in-ten-thousand incremental cancer risk range via ingestion of or direct contact with contaminated residential soils. Background arsenic surface soil levels often exceed applicable limits. Arsenic releases to surface soils (via, e.g., air emissions, waste recycling, soil amendments, direct pesticide application, and chromated copper arsenic (CCA)-treated wood) can result in greatly elevated arsenic levels, sometimes one to two orders of magnitude greater than applicable numerical limits. CCA-treated wood, a heavily used infrastructure material at residences and public spaces, can release sufficient arsenic to result in surface soil concentrations that exceed numerical limits by one or two orders of magnitude. Although significant exceedence of arsenic surface soil numerical limits would normally result in regulatory actions at industrial or hazardous waste sites, no such pattern is seen at residential and public spaces. Given the current risk assessment paradigm, measured or expected elevated surface soil arsenic levels at residential and public spaces suggest that a regulatory health crisis of sizeable magnitude is imminent. In contrast, available literature and a survey of government agencies conducted for this paper finds no verified cases of human morbidity or mortality resulting from exposure to elevated levels of arsenic in surface soils. This concomitance of an emerging regulatory health crisis in the absence of a medical crisis is arguably partly attributable to inadequate government and private party attention to the issue.     

Unintended shootings in a large metropolitan area: an incident-based analysis

STUDY OBJECTIVE: We determine the proportion of unintended shootings that might be prevented by promoting safe storage, safe handling, and/or safer firearm designs. METHODS: A regional firearm injury surveillance system was used to identify fatal and nonfatal unintentional shootings in a 5-county metropolitan area. Case reports were reviewed, and the causes of each shooting were independently classified by 4 members of the research team. A consensus conference was held to resolve disagreements. RESULTS: Between May 1, 1996, and June 30, 2000, 216 cases of unintentional firearm injury were identified, 3.8% of the shootings documented during the study period. Six (2.8%) were fatal. The majority of victims were between 15 and 34 years of age. One fourth (54) of the shootings involved victims younger than 18 years. Handguns were involved in 87% of the incidents. Enough information was available to characterize the incident in 122 (57%) cases. All but 6 fell into 1 or more of 3 broad categories of causation: Child access (14%), mishandling (74%), and/or deficiencies in firearm design (32%). CONCLUSION: Many unintentional shootings could be prevented by promoting safe storage of guns in the home, promoting safe handling of firearms, and requiring that all new handguns incorporate basic safety features.