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.     

Skin to skin contact in neonatal care: knowledge and expectations of health professionals in 2 neonatal intensive care units]

Skin to skin contact is a method derived from kangaroo care whose implementation in industrialized countries has rarely been assessed. OBJECTIVES: To evaluate the barriers, knowledge and expectations of health professionals regarding this care in 2 level III neonatal care units in the Nord-Pas-de-Calais. MATERIALS AND METHODS: Investigation was conducted by means of 2 questionnaires, one intended to physicians, the other to the nursing staff sharing some common questions. The 2 neonatal units differed by the level of implementation of skin to skin contact. Results were compared according to occupation and site of work. RESULTS: 80% of the physicians and 71.4% of the paramedical staff answered to the questionnaires. The difficulties were linked to technical or architectural constraints. Responses were not very different between the 2 teams. The majority (90%) considered this practice as a fully-fledged care. The positive effects on attachment (96% of the answers) were well-known but those on sleep (2,9%), breast-feeding (5%) and pain (0%) were only rarely mentioned. Barriers to implementation were centred on infant's safety. The majority of the team wished to benefit from an educational intervention. DISCUSSION: Although the perception of skin to skin contact was positive in these 2 teams, increased knowledge of the evidence supporting its practice could enable babies and parents to benefit from all its positive effects. The need for educational program was clearly mentioned to improve parents' information. CONCLUSION: This work emphasises the complexity of introducing new procedures in neonatal care particularly in the field of developmental care.     

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.     

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.     

Safety and efficacy of atorvastatin in heart transplant recipients.

BACKGROUND: Pravastatin and simvastatin prolong survival and reduce transplant-related coronary vasculopathy, although low-density lipoprotein (LDL) lowering with these agents is only modest. The objective of this study was to assess the safety of moderate dose atorvastatin and its efficacy when prior treatment with another statin had failed to lower LDL to < 100 mg/dl. METHODS: Data from 185 patients were retrospectively evaluated for adverse events, duration of exposure (person-days), and the mean atorvastatin dose exposure. Changes in lipid parameters, and prednisone and cyclosporine doses were determined. RESULTS: Safety: 48 patients received atorvastatin for 24,240 person-days at a mean dose exposure of 21 +/- 10 mg. Rhabdomyolysis, myositis, myalgias, and hepatotoxicity occurred in 0, 2, 2, and 0 patients, respectively. All events occurred at the 10-mg dose, within the first 3 months, and were rapidly reversible with atorvastatin discontinuation. Efficacy: Thirty-four patients evaluable for efficacy analyses had a pre-atorvastatin LDL of 145 +/- 38 mg/dl on the following statins: pravastatin (n = 30, 40 +/- 0mg), fluvastatin (n = 3, 33 +/- 12 mg), simvastatin (n = 1, 40 mg). After atorvastatin (21 +/- 9 mg/day) for 133 +/- 67 days, LDL was reduced to 97 +/- 24 mg/dl (relative reduction 31 +/- 20%, p < 0.0001). At the end of the observation period (418 +/- 229 days, atorvastatin final dose 24 +/- 14 mg/day), LDL was further decreased to 88 +/- 23 mg (relative reduction 37 +/- 17%, p < 0.0001). CONCLUSION: Atorvastatin, when used at moderate doses and with close biochemical and clinical monitoring, appears to be safe and is effective in aggressively lowering LDL in heart transplant recipients when treatment with other statins has failed to achieve LDL goals.     

HepG2 cell binding activities of different hepatitis b virus isolates: inhibitory effect of anti-HBs and anti-preS1(21–47)

The antigenic relationships among different hepatitis B virus (HBV) isolates were investigated by using monoclonal antibodies (MAbs) specific for HBs, preS2 (pHSA binding site), and preS1 (hepatocyte receptor-binding site) epitopes in a double immunoradiometric assay. In order to define possible functional differences resulting from structural and antigenic differences in the HBV env protein, the HBV isolates were compared in an in vitro cell-binding assay based on the attachment of 125I-labeled HBV to human hepatoma HepG2 cells. We provided evidence for a variability of the expression of preS1 and preS2 specificities in the peplomer (glyco)protein of HBV depending on d/ysubtype of HBsAg, which could affect the viral infectivity. We showed that the integrity of the HBV envelope structure associated with a large expression of preS1(21–47) epitopes is an essential factor for effective binding to HepG2 cells. Interestingly, the HBs-specific MAbs directed to disulfide-bond-dependent epitopes were found to be the best inhibitors of the preS1-HepG2 cell interaction (>50% at the final concentration of 0.5 μg/ml). The MAb F35.25 directed to the preS1(21–47) sequence corresponding to the hepatocyte receptor recognition site was, however, also found to inhibit binding. Thus, our results demonstrate the abilities of both anti-HBs and anti-preS(21–41) to block the attachment of complete HBV particles to HepG2 cells, suggesting that these antibodies should be virus neutralizing and would be expected to confer protection against reinfection.