Dynamics of infant cortical auditory evoked potentials (CAEPs) for tone and speech tokens.

OBJECTIVES: Cortical auditory evoked potentials (CAEPs) to tones and speech sounds were obtained in infants to: (1) further knowledge of auditory development above the level of the brainstem during the first year of life; (2) establish CAEP input-output functions for tonal and speech stimuli as a function of stimulus level and (3) elaborate the data-base that establishes CAEP in infants tested while awake using clinically relevant stimuli, thus providing methodology that would have translation to pediatric audiological assessment. Hypotheses concerning CAEP development were that the latency and amplitude input-output functions would reflect immaturity in encoding stimulus level. In a second experiment, infants were tested with the same stimuli used to evoke the CAEPs. Thresholds for these stimuli were determined using observer-based psychophysical techniques. The hypothesis was that the behavioral thresholds would be correlated with CAEP input-output functions because of shared cortical response areas known to be active in sound detection. DESIGN: 36 infants, between the ages of 4 and 12 months (mean=8 months, s.d.=1.8 months) and 9 young adults (mean age 21 years) with normal hearing were tested. First, CAEPs amplitude and latency input-output functions were obtained for 4 tone bursts and 7 speech tokens. The tone bursts stimuli were 50 ms tokens of pure tones at 0.5, 1.0, 2.0 and 4.0 kHz. The speech sound tokens, /a/, /i/, /o/, /u/, /m/, /s/, and /∫/, were created from natural speech samples and were also 50 ms in duration. CAEPs were obtained for tone burst and speech token stimuli at 10 dB level decrements in descending order from 70 dB SPL. All CAEP tests were completed while the infants were awake and engaged in quiet play. For the second experiment, observer-based psychophysical methods were used to establish perceptual threshold for the same speech sound and tone tokens. RESULTS: Infant CAEP component latencies were prolonged by 100-150 ms in comparison to adults. CAEP latency-intensity input output functions were steeper in infants compared to adults. CAEP amplitude growth functions with respect to stimulus SPL are adult-like at this age, particularly for the earliest component, P1-N1. Infant perceptual thresholds were elevated with respect to those found in adults. Furthermore, perceptual thresholds were higher, on average, than levels at which CAEPs could be obtained. When CAEP amplitudes were plotted with respect to perceptual threshold (dB SL), the infant CAEP amplitude growth slopes were steeper than in adults. CONCLUSIONS: Although CAEP latencies indicate immaturity in neural transmission at the level of the cortex, amplitude growth with respect to stimulus SPL is adult-like at this age, particularly for the earliest component, P1-N1. The latency and amplitude input-output functions may provide additional information as to how infants perceive stimulus level. The reasons for the discrepancy between electrophysiologic and perceptual threshold may be due to immaturity in perceptual temporal resolution abilities and the broad-band listening strategy employed by infants. The findings from the current study can be translated to the clinical setting. It is possible to use tonal or speech sound tokens to evoke CAEPs in an awake, passively alert infant, and thus determine whether these sounds activate the auditory cortex. This could be beneficial in the verification of hearing aid or cochlear implant benefit.

Death adder envenoming causes neurotoxicity not reversed by antivenom--Australian Snakebite Project (ASP-16).

BACKGROUND: Death adders (Acanthophis spp) are found in Australia, Papua New Guinea and parts of eastern Indonesia. This study aimed to investigate the clinical syndrome of death adder envenoming and response to antivenom treatment. METHODOLOGY/PRINCIPAL FINDINGS: Definite death adder bites were recruited from the Australian Snakebite Project (ASP) as defined by expert identification or detection of death adder venom in blood. Clinical effects and laboratory results were collected prospectively, including the time course of neurotoxicity and response to treatment. Enzyme immunoassay was used to measure venom concentrations. Twenty nine patients had definite death adder bites; median age 45 yr (5-74 yr); 25 were male. Envenoming occurred in 14 patients. Two further patients had allergic reactions without envenoming, both snake handlers with previous death adder bites. Of 14 envenomed patients, 12 developed neurotoxicity characterised by ptosis (12), diplopia (9), bulbar weakness (7), intercostal muscle weakness (2) and limb weakness (2). Intubation and mechanical ventilation were required for two patients for 17 and 83 hours. The median time to onset of neurotoxicity was 4 hours (0.5-15.5 hr). One patient bitten by a northern death adder developed myotoxicity and one patient only developed systemic symptoms without neurotoxicity. No patient developed venom induced consumption coagulopathy. Antivenom was administered to 13 patients, all receiving one vial initially. The median time for resolution of neurotoxicity post-antivenom was 21 hours (5-168). The median peak venom concentration in 13 envenomed patients with blood samples was 22 ng/mL (4.4-245 ng/mL). In eight patients where post-antivenom bloods were available, no venom was detected after one vial of antivenom. CONCLUSIONS/SIGNIFICANCE: Death adder envenoming is characterised by neurotoxicity, which is mild in most cases. One vial of death adder antivenom was sufficient to bind all circulating venom. The persistent neurological effects despite antivenom, suggests that neurotoxicity is not reversed by antivenom.

Human anti-snake venom IgG antibodies in a previously bitten snake-handler, but no protection against local envenoming.

We report a 60 year old male bitten by snakes from the Acanthophis genus (Death adder) on two occasions who developed high titres of human IgG antibodies to Acanthophis venom detected at the time of the second bite. The patient was bitten by Acanthophis antarcticus (common death adder) on the first occasion, developed non-specific systemic effects and did not receive antivenom. Three months later he was bitten by Acanthophis praelongus (northern death adder) and he developed significant local myotoxicity associated with a moderate rise in the creatine kinase (maximum 4770 U/L). He was given antivenom 55 h after the bite and recovered over several days. Death adder venom was detected in serum at the time of the first bite, but not the second bite. Human IgG antibodies to death adder were detected on the second admission but not the first. However, despite the presence of antibodies to death adder venom and free venom not being detected, the patient still developed significant local myotoxicity.

Reviewing deaths in the emergency department: deaths in the department or deaths within 48 h.

OBJECTIVES: To investigate an ED death audit process that included deaths occurring within 48 h of admission in addition to deaths in the ED. METHODS: The study was a review of a prospective audit process undertaken in routine clinical practice that included auditing deaths in the ED and deaths of admitted patients within 48 h of ED presentation. Data were extracted from the audit database and included demography, clinical information and medical recommendations. The hospital incident investigation and monitoring system (IIMS) was searched for major incident reports involving death. The main outcome was the number of medical record audits from each group reported to the clinical governance unit for review, and whether the 48 h audit identified relevant cases to the ED in addition to those identified in the ED audit alone. Secondary outcomes were the number of audits resulting in other actions: ED policy review, education, case discussion or review with the inpatient team. RESULTS: Over a 2 year period, 303 deaths were reviewed, including 75 deaths in the ED and 228 deaths within 48 h. The ED auditor recommended no further action in 66/75 (88%) ED deaths and 195/228 (86%) 48 h deaths. A major hospital review was recommended in 4/75 (5%) ED deaths and 11/228 (5%) 48 h deaths, with only 3 and 7 of these, respectively, having been detected by the hospital's IIMS. The audit identified 10 of 13 deaths notified to the IIMS and the remaining 3 did not involve error relevant to the ED. Internal review was recommended in one ED death and eight 48 h deaths. CONCLUSIONS: The present study demonstrates that auditing both ED deaths and 48 h deaths identifies additional issues relevant to the ED compared with auditing ED deaths alone or relying on standard hospital incident reporting.

Single-molecule analysis of DNA-protein complexes using nanopores.

We present a method for rapid measurement of DNA-protein interactions using voltage-driven threading of single DNA molecules through a protein nanopore. Electrical force applied to individual ssDNA-exonuclease I complexes pulls the two molecules apart, while ion current probes the dissociation rate of the complex. Nanopore force spectroscopy (NFS) reveals energy barriers affecting complex dissociation. This method can be applied to other nucleic acid-protein complexes, using protein or solid-state nanopore devices.

RecJ exonuclease: substrates, products and interaction with SSB.

The RecJ exonuclease from Escherichia coli degrades single-stranded DNA (ssDNA) in the 5'-3' direction and participates in homologous recombination and mismatch repair. The experiments described here address RecJ's substrate requirements and reaction products. RecJ complexes on a variety of 5' single-strand tailed substrates were analyzed by electrophoretic mobility shift in the absence of Mg2+ ion required for substrate degradation. RecJ required single-stranded tails of 7 nt or greater for robust binding; addition of Mg2+ confirmed that substrates with 5' tails of 6 nt or less were poor substrates for RecJ exonuclease. RecJ is a processive exonuclease, degrading approximately 1000 nt after a single binding event to single-strand DNA, and releases mononucleotide products. RecJ is capable of degrading a single-stranded tail up to a double-stranded junction, although products in such reactions were heterogeneous and RecJ showed a limited ability to penetrate the duplex region. RecJ exonuclease was equally potent on 5' phosphorylated and unphosphorylated ends. Finally, DNA binding and nuclease activity of RecJ was specifically enhanced by the pre-addition of ssDNA-binding protein and we propose that this specific interaction may aid recruitment of RecJ.

Semicarbazide is a minor thermal decomposition product of azodicarbonamide used in the gaskets of certain food jars.

Evidence is presented for the first time showing that semicarbazide (SEM) is a minor thermal decomposition product of the blowing agent azodicarbonamide (ADC). A novel direct analytical method based on liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESIMS/MS) has been developed to determine SEM in foamed polyvinyl chloride (PVC) seals of metal lids, as well as in commercially available ADC. The direct LC-MS/MS method for gaskets entails extraction of the gaskets in hot water, addition of ((15)N(2)(13)C)-SEM as internal standard, and injection of an aliquot directly into the LC-MS system, achieving good sensitivity (S/N = 348 for 2 ng injected on-column) and monitoring three characteristic mass transitions (m/z 76-->31; 76 -->44; 76-->59). Semicarbazide can be detected in thermally treated ADC, reaching up to 0.93 mmol mol(-1) at 220 degrees C, as determined by the direct LC-MS/MS method. This new method is also compared to the classical derivatization method using 2-nitrobenzaldehyde (2-NBA) that is routinely employed to determine SEM as an indicator of the usage of the antimicrobial drug nitrofurazone, the use of which is not authorized in the European Union (EU). Both methods revealed proportional results, with approx. 3-fold higher levels recorded by the direct SEM approach, probably due to differences in the extraction procedures used. A limited survey of plastic seals from used press twist and twist-off metal lids on food jars (non-foamed and foamed) revealed levels of SEM ranging from 2 to 8689 microg kg(-1)(average = 1593 microg kg(-1), n= 57 determinations).