Maturation of Startle Modulation

This study of the maturation of prestimulation-induced modulation of startle in 3 to 8 year old children and adults demonstrated significant effects of age on both startle magnitude and onset latency. Startle was evoked by 104dB(SPL) 50-ms bursts of white noise, and the amplitude and onset latency of the blink reflex were measured after integration of the obicularis oculi EMG. Prestimulation with 75dB 1000 Hz tones resulted in severe inhibition of both amplitude and latency in adults when 20-ms tones preceded the startling stimuli by 120 ms or 250 ms. Following sustained prestimulation for 2000 ms, the adults showed modest nonsignificant response facilitation. Eight-year-old children showed mature inhibitory and facilitatory startle amplitude modulation, but significantly less inhibition and more facilitation of onset latency compared to adults. Preschool children showed significantly less amplitude and latency inhibition and more facilitation than 8-year-olds and adults. In response to prestimulation 120 ms before startling stimuli, the preschool children actually showed latency facilitation. Modulation of startle by prestimulation is mediated by brainstem neuronal networks. These findings suggest that brainstem mechanisms which mediate startle response modulation undergo development during early childhood and do not mature until about 8 years of age.     

A group-specific,indirect sandwich ELISA for the detection of equine encephalosis virus antigen

A polyclonal antibody-based, group-specific, indirect, sandwich ELISA (S-ELISA) for the detection of equine encephalosis virus (EEV) antigen was developed. Purified EEV particles were titrated in the S-ELISA and the limit of detection was determined to be approximately 9.0 ng of antigen/ml (0.45 ng/well). Positive S-ELISA reactions were recorded with seven serologically distinct EEV serotypes. No cross-reactions were recorded with other arboviruses including African horse sickness virus (AHSV) serotypes 1-9, bluetongue serotypes 1-24, epizootic haemorrhagic disease serotypes 1-8 and isolate 318, and selected isolates of Palyam, Eubenangee, Corriparta, Warrego, Akabane and bovine ephemeral fever viruses. The assay proved to be sensitive and specific for the rapid detection of EEV in cell cultures and in homogenated suckling mouse brain (MB). The data generated in this study suggest that the ELISA will be valuable for epidemiological studies of EE and will assist in making a reliable differential diagnosis between EEV and AHSV infections.     

Routine mortality monitoring for detecting mass murder in UK general practice: test of effectiveness using modelling.

BACKGROUND: The Shipman Inquiry recommended mortality rate monitoring if it could be 'shown to be workable' in detecting a future mass murderer in general practice. AIM: To examine the effectiveness of cumulative sum (CUSUM) charts, cross-sectional Shewhart charts, and exponentially-weighted, moving-average control charts in mortality monitoring at practice level. DESIGN OF STUDY: Analysis of Scottish routine general practice data combined with estimation of control chart effectiveness in detecting a 'murderer' in a simulated dataset. METHOD: Practice stability was calculated from routine data to determine feasible lengths of monitoring. A simulated dataset of 405,000 'patients' was created, registered with 75 'practices' whose underlying mortality rates varied with the same distribution as case-mix-adjusted mortality in all Scottish practices. The sensitivity of each chart to detect five and 10 excess deaths was examined in repeated simulations. The sensitivity of control charts to excess deaths in simulated data, and the number of alarm signals when control charts were applied to routine data were estimated. RESULTS: Practice instability limited the length of monitoring and modelling was consequently restricted to a 3-year period. Monitoring mortality over 3 years, CUSUM charts were most sensitive but only reliably achieved >50% successful detection for 10 excess deaths per year and generated multiple false alarms (>15%). CONCLUSION: At best, mortality monitoring can act as a backstop to detect a particularly prolific serial killer when other means of detection have failed. Policy should focus on changes likely to improve detection of individual murders, such as reform of death certification and the coroner system.     

Relation between raised concentrations of fucose, sialic acid, and acute phase proteins in serum from patients with cancer: choosing suitable serum glycoprotein markers.

Serum concentrations of fucose, sialic acid, and eight acute phase proteins were measured in single specimens from patients with cancer in order to determine whether the raised concentrations of protein bound sugars commonly found in cancer correlate with increased concentrations of the acute phase proteins. Strong positive correlations were found only with alpha 1-acid glycoprotein, alpha 1-antitrypsin, and haptoglobins. Changes in protein bound sugars and acute phase proteins were also examined in relation to patients' disease states. Serum fucose was raised more often in patients with advanced disease than in those in whom the spread of the tumour was more restricted; increased sialic acid concentrations, however, were found with a similar frequency in both these groups. Combined use of fucose and sialic acid values gave a high degree of marker positivity which could be only slightly improved on by including measurement of acute phase proteins. The combined use of serum fucose and sialic acid concentrations may have value in monitoring patients with cancer: the sialic acid provides an index of the acute phase response and the fucose a measure of the tumour spread.     

Decline in perinatal HIV transmission in New York State (1997-2000)

BACKGROUND: Perinatal HIV transmission has declined significantly in New York State (NYS) since implementation of a 3-part regimen of zidovudine prophylaxis in the antenatal, intrapartum, and newborn periods. This study describes the factors associated with perinatal transmission in NYS from 1997 to 2000, the first 4 years of NYS's comprehensive program in which all HIV-exposed newborns were identified through universal HIV testing of newborns. METHODS: This population-based observational study included all HIV-exposed newborns whose infection status was known and their mothers identified in NYS through the universal Newborn HIV Screening Program (NSP) from February 1997 to December 2000. Antepartum, intrapartum, newborn, and pediatric medical records of HIV-positive mothers/infants were reviewed for history of prenatal care, antiretroviral therapy (ART), and infant infection status. Risks associated with perinatal HIV transmission were examined. RESULTS: Perinatal HIV transmission declined significantly from 11.0% in 1997 to 3.7% in 2000 (P < 0.05). Prenatal ART was associated with a decline in perinatal HIV transmission both for monotherapy (5.8%, relative risk [RR] = 0.3, 95% confidence interval: 0.2%-0.5%) and combination therapy [2.4%, RR = 0.1, 95% confidence interval: 0.1%-0.2%) compared with no prenatal antiretroviral prophylaxis (P < 0.05). CONCLUSIONS: Public health policies to improve access to care for pregnant women and advances in clinical care, including receipt of appropriate preventive therapies, have contributed to declines in perinatal HIV transmission in NYS.     

Yohimbine bioavailability in humans

Summary Pharmacokinetic profiles were determined in seven healthy young male subjects following single oral and intravenous doses of 10 mg of yohimbine hydrochloride.The drug was rapidly eliminated (t_1/2 0.58 h orally and t_1/2 0.68 h intravenously). Following intravenous administration the data fit a two-compartment pharmacokinetic model, with a very rapid distribution phase (t_1/2a was approximately 6 min). Both the oral and the intravenous yohimbine clearance values were high but oral clearance values were much higher (mean 9.77 ml·min^–1·kg^–1 intravenous versus 55.9 ml·min^–1·kg^–1 oral). The oral bioavailability showed great variability, ranging from 7% to 87% (mean value was 33%).The imcomplete oral bioavailability of yohimbine may reflect either incomplete absorption from the gastrointestinal tract or an hepatic first pass effect. Although yohimbine is rapidly absorbed when given orally, the bioavailability is quite variable and considerable individualization of dosing may be necessary when the drug is used orally for clinical indications.Supported in part by NIH grant # MOIRR 0042     

Vineland Adaptive Behavior Scale Scores as a Function of Age and Initial IQ in 210 Autistic Children

Human growth modeling statistics were utilized to examine how Vineland Adaptive Behavior Scale (VABS) scores changed in individuals with autistic disorder as a function of both age and initial IQ. Results revealed that subjects improved with age in all domains. The rate of growth in Communication and Daily Living Skills was related to initial IQ while rate of growth in Social Skills was not. Results should provide hope for parents and further support for the importance of functional social-communication skills in the treatment of autism.