An evaluation of numerical integration algorithms for the estimation of the area under the curve (AUC) in pharmacokinetic studies

Six numerical integration algorithms based on linear and log trapezoidal methods as well as four cubic-spline methods were proposed for estimation of area under the curve (AUC). These six different algorithms were implemented using IMSL/IDL^TM command language and evaluated using data simulated under five different dosing conditions and two different sampling conditions. Comparisons between AUC estimations using these six different algorithms and the theoretical results were made in terms of both overall AUC values and the superimposability of the concentration-time profiles. In well designed studies with ample data points, the algorithm based on IMSL/IDL^TM function CSSHAPE with concavity preservation gave the best performance. In contrast, when the frequency of blood collection was limited, the algorithm based on the log trapezoidal rule proved to be stable with reasonable accuracy, and is recommended as the practical method for numerical interpolation and integration in pharmacokinetic studies. Algorithms based on the combination of the log trapezoidal rule and cubic-spline methods using IMSL/IDL^TM function CSSHAPE can be developed to enhance overall performance.     

In Vivo Proton Spectroscopy of Intracranial Infections and Neoplasms

The chemical characteristics of 10 neoplastic and 11 infectious brain masses were studied by in vivo ¹H magnetic resonance spectroscopy. In tumors, peak height ratios of n-acetyl-L-aspartate to choline were decreased compared to those in normal brain tissue and infectious masses (p < 0.02), but the ratios in normal brains and those with infections did not differ. N-acetyl-L-aspartate—to-creatine/phosphocreatine ratios were significantly lower in infectious masses and tumors compared to normal brain tissue (p = 0.003). However, in progressive multifocal leukoencephalopathy, N-acetyl-L-aspartate appeared relatively unchanged. Lactate was greater than choline in 9 of 11 brains with infection, 0 of 14 control brains, and 1 of 10 tumors. Lactate-to-choline ratios were significantly elevated in infectious masses compared with tumors (p < 0.01). ¹H magnetic resonance spectroscopy is promising for the noninvasive diagnosis of focal brain masses.     

Supportive employment for individuals with chronic schizophrenia: the case for a National Health Service community-based sheltered workshop

A pilot project was established from 1992 to 1994 to provide people with chronic schizophrenia living in Dundee, Scotland, with a National Health Service sheltered workshop that would be fully integrated into the local business community. Of the 43 clients who attended the sheltered workshop, 38 agreed to take part in the project. Typical attenders were single, middle-aged men with schizophrenia. Twenty-five per cent had spent more than two years in hospital; 75% had been unemployed for more than five years. The clients' use of National Health Service day facilities more than halved while attending the workshop. Their hospital readmission rates were low (16%) compared with the local readmission rates for people with schizophrenia in Dundee (86%). A training approach based on the general principles of social skills training contributed to positive vocational outcomes for one-third of the workshop clients. The findings suggest that the onus of responsibility for providing work for many individuals with schizophrenia remains with the National Health Service, and in particular, occupational therapy. Occupational therapy staff must assess their clients effectively and provide quality training leading to opportunities for paid employment. These results have implications for the training of occupational therapy staff and also for the staffing structure in sheltered workshops. Copyright © 1997 Whurr Publishers Ltd.     

Evaluation of a clinical case definition of AIDS in African children

In July 1986, a provisional clinical case definition of AIDS in children, developed by the World Health Organization (WHO) for surveillance purposes in Africa, was tested on 159 patients hospitalized in the Department of Pediatrics at Mama Yemo Hospital, Kinshasa, Zaire. Twenty-one (13%) of these children were seropositive for HIV. In this population, the clinical case definition of pediatric AIDS was found to be fairly specific (87%) but lacked sensitivity (35%). The positive predictive value for HIV seropositivity was 25%. This study suggests that it is more difficult to define AIDS clinically in children than in adults and that the utility of the proposed WHO clinical case definition for pediatric AIDS for surveillance of children's AIDS in Africa is limited.     

Follow up and evaluation of the Victorian first-trimester combined screening programme for Down syndrome and trisomy 18

Objective  The objective of this study was to follow up and evaluate the statewide first-trimester combined screening programme for Down syndrome and trisomy 18 at Genetic Health Services Victoria, Australia.
Design  Retrospective population cohort.
Setting  Maternal Serum Screening Laboratory records.
Sample  All women screened between February 2000 and June 2002 (16 153 pregnancies).
Methods  Screening results were matched to Victorian perinatal and birth defect data via record linkage, with an ascertainment of 96.8% of pregnancy outcomes. Manual follow up with health professionals increased ascertainment to more than 99%.
Main outcome measures  Fetal Down syndrome or trisomy 18, and combined screen results, to calculate test characteristics.
Results  Using a risk threshold of 1 in 300 at time of ultrasound, the sensitivities for standard first-trimester combined screening and augmented 13-week combined screening for Down syndrome were 87.3 and 90.5% and the false-positive rates (FPR) were 4.1 and 3.9%, respectively. The sensitivity for trisomy 18 was 66.7% (10/15, 95% CI 42.8–90.5%) with a 0.4% FPR and 15.2% positive predictive value (1 in 250 risk threshold).
Conclusions  The combined use of record linkage and manual follow-up techniques was effective in ascertaining more than 99% of pregnancy outcomes for calculations of accurate test characteristics of the combined screen. The sensitivity for Down syndrome at Genetic Health is comparable to similar populations. However, the sensitivity for trisomy 18 is lower than that elsewhere, which may reflect the overall low birth prevalence of trisomy 18 and associated small numbers in this particular cohort.     

OXYGEN FREE RADICAL IN HUMAN OSTEOARTHRITIS

The xanthine oxidase catalysed release of superoxide free radicals (O2-) from endogenous hypoxanthine was determined in homogenates of synovium obtained from three groups of patients, those undergoing primary or revision total hip replacement (THR) for osteoarthritis and those undergoing arthroscopy of the knee for semilunar disc injuries. The concentrations of hypoxanthine in homogenates obtained during THR were found to be significantly higher than those in the group with semilunar disc injuries. The results suggest that there is a greater predisposition to free radical release and tissue damage in osteoarthritis.     

Conjunctival granuloma caused by surgical talc.

Talc from surgical gloves has been known to be a cause of granulomas within the surgical cavity. We report a case in which recurrent conjuntival inflammation was found to be caused by talc.