The relationship between nerve fiber layer and perimetry measurements

PURPOSE: Losses of retinal ganglion cells (RGCs) in glaucoma are the cause of visual field defects and thinning of the retinal nerve fiber layer (RNFL), but methods of correlating these events have not been developed. The present study was conducted to investigate the relationship between standard automated perimetry (SAP) measures of RGCs and optical coherence tomography (OCT) measures of the ganglion cell axons entering the optic nerve from corresponding visual field locations. METHODS: SAP and OCT data from normal monkeys were used to develop methods for estimating neuron counts and mapping SAP visual field locations onto the optic nerve head (ONH). The procedures developed for normal eyes were applied to monkeys with experimental glaucoma. RESULTS: The number of neurons derived from SAP and OCT data for normal eyes were in close agreement. The estimates of the number of RGCs in retinal areas of the Humphrey Field Analyzer 24-2 (Carl Zeiss Meditec, Inc., Dublin, CA) visual field and the axons entering the ONH were both approximately 1.5 million. The neural losses derived from subjective and objective measurements in monkeys with early experimental glaucoma correlated highly, with a mean +/- SD difference of 0.6% +/- 22% between the two estimates in control eyes and 3% +/- 24% in laser-treated eyes. CONCLUSIONS: SAP measures of visual field defects and OCT measures of RNFL defects are correlated measures of glaucomatous neuropathy. The normal intersubject variability and the dynamic ranges of the measurements suggest that RNFL thickness may be a more sensitive measurement for early stages and perimetry a better measure for moderate to advanced stages of glaucoma.     

Simultaneous Quantification of Baricitinib and Methotrexate in Rat Plasma by LC-MS/MS: Application to a Pharmacokinetic Study

Efficacy assessments using a combination of baricitinib and methotrexate necessitate the development of an analytical method for the determination of both drugs in plasma with precision. A high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of baricitinib and methotrexate in rat plasma. Extraction of baricitinib, methotrexate, and tolbutamide (internal standard; IS) from 50 µL of rat plasma was carried out by protein precipitation with methanol. Chromatographic separation of the analytes was performed on the YMC pack ODS AM (150 mm × 4.6 mm, 5 µm) column under gradient conditions with methanol: 2.0 mM ammonium acetate buffer as the mobile phases at a flow rate of 1 mL/min. The precursor ion and product ion transition for both analytes and IS were monitored on a triple quadrupole mass spectrometer, operated with selective reaction monitoring in positive ionization mode. The method was validated over a concentration range of 0.5–250.00 ng/mL for baricitinib and methotrexate. Mean extraction recoveries for baricitinib, methotrexate, and IS of 86.8%, 89.4%, and 91.8% were consistent across low, medium, and high QC levels, respectively. Precision and accuracy at low, medium, and high quality control levels were less than 15% across the analytes. Benchtop, wet, freeze-thaw, and long-term stability were evaluated for both of the analytes. The analytical method was applied to support the pharmacokinetic study of simultaneous estimation of baricitinib and methotrexate in Wistar rats. Assay reproducibility was demonstrated by reanalysis of 18 incurred samples     

Genome‐wide association study of theta band event‐related oscillations identifies serotonin receptor gene HTR7 influencing risk of alcohol dependence

Event‐related brain oscillations (EROs) represent highly heritable neuroelectrical correlates of human perception and cognitive performance that exhibit marked deficits in patients with various psychiatric disorders. We report the results of the first genome‐wide association study (GWAS) of an ERO endophenotype—frontal theta ERO evoked by visual oddball targets during P300 response in 1,064 unrelated individuals drawn from a study of alcohol dependence. Forty‐two SNPs of the Illumina HumanHap 1 M microarray were selected from the theta ERO GWAS for replication in family‐based samples (N = 1,095), with four markers revealing nominally significant association. The most significant marker from the two‐stage study is rs4907240 located within ARID protein 5A gene (ARID5A) on chromosome 2q11 (unadjusted, Fisher's combined P = 3.68 × 10^?6). However, the most intriguing association to emerge is with rs7916403 in serotonin receptor gene HTR7 on chromosome 10q23 (combined P = 1.53 × 10^?4), implicating the serotonergic system in the neurophysiological underpinnings of theta EROs. Moreover, promising SNPs were tested for association with diagnoses of alcohol dependence (DSM‐IV), revealing a significant relationship with the HTR7 polymorphism among GWAS case–controls (P = 0.008). Significant recessive genetic effects were also detected for alcohol dependence in both case–control and family‐based samples (P = 0.031 and 0.042, respectively), with the HTR7 risk allele corresponding to theta ERO reductions among homozygotes. These results suggest a role of the serotonergic system in the biological basis of alcohol dependence and underscore the utility of analyzing brain oscillations as a powerful approach to understanding complex genetic psychiatric disorders. © 2010 Wiley‐Liss, Inc.     

Can Subfascial Endoscopic Perforator Surgery (SEPS) be Standard of Care in Advanced Chronic Venous Insufficiency (CVI)?

Hellenic Journal of Surgery - Subfascial Endoscopic Perforator Surgery (SEPS) is a minimally invasive technique to treat incompetent perforating veins. Thirty patients with advanced chronic venous...     

At issue: management of medication noncompliance in schizophrenia by families in India

Noncompliance with medication during a symptomatic phase is a common problem in the treatment of schizophrenia patients. In India, a majority of patients live with their families and those families supervise patients' medication intake. In a study of patients attending an urban outpatient care center in India, it was noted that when the patients were acutely ill and refused to take medication, the families administered medication to them without patients' knowledge, under the supervision of the psychiatrist. This method had been practiced by families in half the cases of patient noncompliance. Many families felt that there was no other viable alternative under the circumstances. Only a minority of patients was aware of having received medication through this method, and many of them reacted negatively to it. However, the patients were subsequently taking treatment voluntarily following the reduction in the severity of the behavioral disorder with the involuntary treatment. The issues involved in this form of treatment are discussed with regard to the social and health care environment in the country.     

Alcoholism is a disinhibitory disorder: neurophysiological evidence from a Go/No-Go task

Response inhibition is considered a core dimension in alcoholism and its co-existing disorders. The major objective of this study is to compare the magnitude and spatial distribution of ERP components during response activation and inhibition in alcoholics (N = 30) and normal controls (N = 30) using a visual Go/No-Go task. The results indicate that alcoholics manifest a decreased P3(00) amplitude during Go as well as No-Go conditions. The difference between Go and No-Go processing was more evident in controls than in alcoholics. The topography of current source density in alcoholics during the P3 response was found to be very different from that of normals, suggesting that alcoholics perhaps activated inappropriate brain circuitry during cognitive processing. The significantly reduced No-Go P3 along with the relatively less anteriorized CSD topography during No-Go condition suggests poor inhibitory control in alcoholics. It is proposed that the No-Go P3, the electrophysiological signature of response inhibition, can be considered as an endophenotypic marker in alcoholism.     

Racial differences in the outcome of patients with colorectal carcinoma

BACKGROUND: African-American (AA) patients with colorectal carcinoma have a worse prognosis compared with Caucasians. To analyze the causes of this disparity in survival, a retrospective study of patients with colorectal carcinoma was undertaken. The impact of treatments received and the role of socioeconomic factors such as income, education, and poverty levels were studied. METHODS: A retrospective analysis of patients with colorectal carcinoma at a single institution was conducted. The overall survival of AA and Caucasians, stage at presentation, treatment received, and socioeconomic factors were analyzed using the institutional tumor registry and 1990 census data. RESULTS: The overall survival of AA patients was worse compared with Caucasians, both due to all causes (P < 0.001) and cancer-related deaths (P < 0.001). The relative risk of death due to all causes was 1.4 (95% confidence interval [CI] 1.2-1.8) for AA, 4.3 for patients with Stage IV disease (95% CI 3.2-5.7), and 2.3 for patients not undergoing surgery (95% CI 1.7-3.1). After multivariate adjustment for gender, site, socioeconomic factors, and therapeutic modalities, the relative risks for death were 1.5 (95% CI 1.2) for AA, 1.4 (95% CI 1.1-1.7) for patients 60 years of age or older, and 4.2 (95% CI 3.4-5.2) for Stage IV disease. The survival difference between AA and Caucasians was not influenced by income, poverty level, and education. African Americans were treated less frequently with chemotherapy and radiation therapy compared with their Caucasian counterparts. CONCLUSIONS: African American patients with colorectal carcinoma have a poorer prognosis compared with Caucasians. This discrepancy may be due to decreased utilization of chemotherapy and radiation therapy. Socioeconomic factors and lack of access to health care do not entirely explain the worse prognosis of AA. These factors should be identified and dealt with to improve the health care of AA patients with various malignant disorders.     

Effect of monocrotophos and quinalphos on soil population and nitrogen-fixing activity of Azospirillum sp

The effects of monocrotophos and quinalphos on population and nitrogen-fixing activity of Azospirillum sp. in four agricultural soils were determined in a laboratory study. Concentrations of the two insecticides up to a 5 kg ha-1 level were either stimulatory or innocuous to the population of Azospirillum in the soils. Four successive applications of the insecticides to soils resulted in a significant increase in the population density. Cultures of Azospirillum sp., isolated from insecticide-treated soils, exhibited greater nitrogen-fixing activity. Three consecutive subculturings of the isolates from insecticide-treated soils had no effect on their nitrogen-fixing activity.     

Heritability of Bipolar EEG Spectra in a Large Sib-pair Population

The additive genetic heritability of both monopolar and bipolar EEG spectral power in a sample of 305 non-twin sibships comprising 690 individuals (age range 7–65) was estimated in order to investigate their regional variation. The heritabilities of the bipolar EEG spectral power ranged from 0.10 to 0.63 in 38 electrode-pairs, and those of monopolar power ranged from 0.23 to 0.68 in 19 electrodes in six frequency bands from theta to high beta. The bipolar data shows significantly greater topographic variation compared to that of the monopolar data. The mean of bivariate genetic correlations were consistently lower for the bipolar data and the coefficients of variation consistently higher when compared to those of the monopolar data for each of the frequency bands. The results from the bipolar derivations are in greater accord with genetic findings in brain anatomy and show the possibility of multiple genetic sources for the phenotypic variability of EEG activity. Edited by Danielle Posthuma This work was supported by NIAAA Investigator-Initiated Interactive Research Project Grant (IRPG): AA 12560 at SUNY Downstate Medical Center, AA 12555 at Indiana University School of Medicine, grant AA 12557 at Washington University School of Medicine, and AA 12553 at Howard University. We would like to dedicate this paper to the memory of Henri Begleiter, who initiated its writing, and whose death during its preparation only inspired us to continue to follow the high scientific standards which his work exemplified.