Assays for HIV with improved sensitivity and specificity

Increased knowledge of the human immunodeficiency virus (HIV) and the infection it causes in humans has resulted in an enormous expansion in the understanding of viral parameters and host changes. HIV is a virus which mutates readily and rapidly, presenting many challenges to assay developers, and monitors of therapy and drug-resistance. Prolific viral replication at all the stages of the disease means that an accurate assessment of viral burden, viral load and changes to immune system markers is essential for effective clinical management and treatment. In the present review we have summarised current opinion on the kinetics of HIV infection and the pathogenesis of the disease it causes, and have provided a background to the evolution of HIV assays. Sensitivities and specificities of assays used for anti-HIV and HIV detection have improved, and new assays have been developed employing novel molecular techniques, which are being applied to meet continually evolving demands for more sensitive measurement of an increasing number of parameters. The future of HIV testing is also considered in the light of new knowledge concerning virus dynamics in vivo, the likelihood of the emergence of new subtypes and the changing approach to therapy. Assays will be, on the whole, used to quantify virus and to measure the host reactions to infection, often in the presence of antivirals. Thus, extreme sensitivity and specificity will be required.     

Measurement of basal tear turnover using a standardized protocol

Background: The aim of this study was to compare basal tear turnover values of healthy volunteers in different countries. Methods: Healthy volunteers aged between 20 and 70 years were selected in three European cities. Basal tear turnover values were calculated according to a standardized protocol from the decay of the fluorescein concentration in tears after instillation of 1-l drop of fluorescein in the conjunctival sac. Fluorescein concentration was measured with identical commercial fluorophotometers. A monoexponential decay of fluorescein was assumed to represent basal tear flow. Results: The mean tear turnover values were 13.1%/ min ± 4.6 SD (n=4), 16.0%/ min ± 5.2 SD (n=24) and 17.5%/ min ± 3.4 SD (n = 20) in Clermont-Ferrand (France), Leiden (The Netherlands) and Madrid (Spain), respectively. The differences between the values were not significant (Mann-Whitney test P > 0.09). Conclusions: The tear turnover in the different cities was similar. The methods used were simple and the software easy to use.Concerted Action, supported in part by the European Commission, on Ocular Fluorometry: Standardization and Instrumentation Development of the 4th European Community Medical and Health Research Programme (No. MR 4*/0314/P).     

Effectiveness of a social influences smoking prevention program as a function of provider type, training method, and school risk

OBJECTIVES: This study determined the effect of provider (nurse or teacher) and training method (workshop or self-preparation) on outcomes of a social influences smoking prevention program. METHODS: One hundred elementary schools were stratified by school risk score (high risk = high smoking rate among senior students) and assigned randomly to conditions: (1) teacher/self-preparation, (2) teacher/workshop, (3) nurse/self-preparation, (4) nurse/workshop, and (5) control. Intervention occurred in grades 6 to 8. Smoking status at the end of grade 8 was the primary endpoint variable. RESULTS: Intervention reduced grade 8 smoking rates in high-risk schools (smoking rates of 26.9% in control vs 16.0% in intervention schools) but not in low-risk schools. There were no significant differences in outcome as a function of training method and no significant differences in outcome between teacher-provided and nurse-provided interventions in high- and medium-risk schools. Although nurses achieved better outcomes than did teachers in low-risk schools, neither provider type achieved outcomes superior to the control condition in those schools. CONCLUSIONS: Workshop training did not affect outcomes. Teachers and nurses were equally effective providers. Results suggest that programming should target high-risk schools.     

Volumetric magnetic resonance imaging study of the brain in subjects with sex chromosome aneuploidies

OBJECTIVES: Cognitive impairment has been reported in people with sex chromosome aneuploides (SCAs) and it has been proposed that the presence of an extra sex chromosome may have an adverse effect on neurodevelopment. This study examines the hypothesis with structural MRI of the brain. METHODS: Thirty two subjects with SCA (XXX (n=12), XYY (n=10), and XXY (n=10)) from a birth cohort study were matched groupwise for age, parental social class, and height with normal controls (13 female, 26 male). Brain MRI, measurements of IQ, and a structured psychiatric interview were performed. RESULTS: The XXX females and XXY males had significantly smaller whole brain volumes than controls of the same phenotypic sex (p=0.003 and p相似文献   

Placing hippocampal single-unit studies in a historical context.

A profound increase in the study of the role of the hippocampus in behavior and cognitive processing resulted from the startling discovery by O'Keefe and Dostrovsky in 1971 that hippocampal neurons fire selectively in different regions or "place fields" of an environment. That discovery spawned a comprehensive theory of hippocampal function that was elucidated in the publication, The Hippocampus as a Cognitive Map by O'Keefe and Nadel in 1978. According to the theory, the hippocampus serves as the neural substrate for maps of allocentric space. The goal of this paper is to revisit the historical background for the development of the cognitive map theory and to examine the context in which the theory and the phenomenon of place field activity began to gain acceptance by the scientific community. While subsequent research has led some to question if the theory can adequately account for all consequences of hippocampal lesions and all the correlates of hippocampal cellular activity, it is clear the theory has stood the test of time and has been successful in generating an enormous amount of fruitful research.     

Risk factors for rape, physical assault, and posttraumatic stress disorder in women: examination of differential multivariate relationships

The National Women's Study, a 2-year, three-wave longitudinal investigation, employed a national probability sample of 3,006 adult women to: (a) identify separate risk factors for rape and physical assault, and (b) identify separate risk factors associated with post-rape posttraumatic stress disorder (PTSD) and post-physical assault PTSD. This investigation differed from previous studies in that it prospectively examined risk factors at the multivariate, as opposed to univariate level. Overall, past victimization, young age, and a diagnosis of active PTSD increased women's risk of being raped. By contrast, past victimization, minority ethnic status, active depression, and drug use were associated with increased risk of being physically assaulted. Risk factors for PTSD following rape included a history of depression, alcohol abuse, or experienced injury during the rape. However, risk factors for PTSD following physical assault included only a history of depression and lower education.     

beta-lactam antibiotics. II. Structure-activity relationships of 6-[alpha-(alpha'-ureido-acylamino) acylamino] penicillanic acids.

The influence on the structure-activity relationships (S.A.R.) of the stereochemistry and various alkyl, aryl, aralkyl and heterocyclic substituents at the two chiral centres in the dipeptide side-chain of a new series of penicillins was examined. In many cases the effects of these changes had a pronounced influence on the degree of activity against Gram-positive and especially Gram-negative bacteria. Several compounds indicated that the size, shape and spatial disposition of a substituent were the parameters of importance in influencing activity, rather than it lipophilic or electronic character. The most active homologues in the series provided broad-spectrum penicillins which in terms of their in vitro antibacterial properties showed improvements over certain of the marketed penicillins. Thus 6-[D-alpha(alpha'-ureidoacyl-amino)acylamino]penicillanic acids were found which had a carbenicillin-like profile, with improvements against Pseudomonas aeruginosa, Klebsiella aerogenes, sensitive and beta-lactamase-producing Gram-positive cocci.     

Renotrophic factors in urine

Our previous observations of increased renal protein synthesis in rats subjected to the constant intravenous reinfusion of half their urine output has suggested that the circulatory retention of renotrophic factors in urine is capable of stimulating renal growth. In the present studies, using this same model of "half-urine-reinfusion," which is designed to produce a selective halving of renal excretory function, we have demonstrated significant increases in total DNA content and the incorporation of tritiated thymidine in renal DNA. In addition, a bioassay method was developed in which an assay rat, given an intravenous infusion of urine from another rat, exhibited increases in the incorporation of thymidine into renal DNA and the incorporation of radiolabelled choline into renal phospholipid. This renotrophic activity in the urine was only minimally decreased by heating to 100 degrees C for 30 min and was confined to ultrafiltration fractions retained on a membrane with a nominal 10,000-dalton solute rejection. Removal of one kidney from the rats from which the urine was obtained led to only a modest and transient reduction in the excretion of renotrophic activity, suggesting that the urinary renotrophic factors are of circulatory, not renal, origin. Isolated renal cortical fragments incubated with an ultrafiltration retentate of urine displayed a dose-dependent increase in choline incorporation into phospholipid, suggesting a direct action of the factors on kidney tissue. Finally, no evidence of stimulation of either DNA or phospholipid synthesis could be seen in hepatic tissue.(ABSTRACT TRUNCATED AT 250 WORDS)     

Simulation of emergency medical service scheduling

Efficient allocation of resources is essential in any activity, but experimenting to determine appropriate levels risks a reduction in services that could be dangerous in a healthcare operation. Computer simulations offer a risk-free environment for testing alternate resource levels and balancing costs and services. This article describes the use of a simulation to determine appropriate staffing levels for an emergency medical service.