Once-daily versus multiple-daily gentamicin in infants and children

In this prospective randomized trial, the efficacy and safety of once-daily administration of gentamicin were compared with multiple-daily administration in infants and children. In addition, pharmacokinetic variables were calculated. Gentamicin therapy was started at a dose of 5 mg/kg per day under individual dose or dosage interval adjustments to achieve target levels. Fifty-two infants and children aged 1 month (postterm) to 16 years were enrolled. The duration of fever from the start of therapy, the percentage decline of C-reactive protein (CRP) on day 3 of treatment, and the clinical outcome were used as efficacy parameters. Nephrotoxicity was evaluated using creatinine serum levels. Basic characteristics in both groups were comparable. A good clinical response was observed in both groups. Fever may have resolved faster with multiple-daily administration, but this was not statistically significant. The percentage of decline of CRP was also comparable in both groups. Nephrotoxicity occurred in six patients, three per group. Many patients were too ill or too young to perform hearing tests, but no clinical signs of ototoxicity were observed. Mean doses of 6.8 mg/kg per day (multiple-daily administration) and 7.3 mg/kg per day (once-daily administration) were necessary to meet the target gentamicin levels. Triple-daily doses had to be reduced to a twice-daily regimen in 17 of 26 children. Dose and dosage interval adaptations can be performed by Bayesian forecasting using a one-compartment model with one set of K(e) and V(d) parameters. The authors consider both regimens equally effective, with a comparable incidence of nephrotoxicity. A starting dose of 6.5 mg/kg once daily is advised.     

Epstein-Barr virus related central nervous system lymphoma in a child after renal transplantation

In this report, we describe the development of a rapidly progressive Epstein-Barr virus (EBV) related cerebral lymphoma in an 11 year old girl, eight months after renal transplantation. No serological evidence for a persistent EBV infection was found, but Epstein-Barr nuclear antigen (EBNA) could be demonstrated in the tumor. The clinical course of our patient was different from EBV-related syndromes in renal transplanted patients described in previous reports. Furthermore, pathological investigations of the biopsy specimen and tumor cells obtained at necropsy revealed a discrepancy in light chain expression. The possibility that lymphoproliferative disorders represent multiclonal B cell lymphomas is discussed.     

Tobramycin-containing bone cement and systemic cefazolin in a one-stage revision. Treatment of infection in a rabbit model.

The efficacy of tobramycin-containing bone cement with that of systemic cefazolin for treatment of infection in a one-stage revision model is compared. In addition, the value of detecting bacterial DNA after antibiotic treatment was investigated. An implant was inserted into the right tibia of rabbits after inoculation with Staphylococcus aureus. At 28 days, the implant was removed. Subsequently, either plain bone cement with or without systemic administration of cefazolin, or tobramycin-containing bone cement was injected into the medullary canal. The tibiae were cultured 14 days after revision (Day 42), and showed a significant decrease in bacterial counts for both antibiotic groups compared with the control group (p相似文献   

Effects of hydrosyapatite coating on Ti-6A1-4V implant-site infection in a rabbit tibial model.

To investigate the effect of implant type after direct contamination, a hydroxyapatite-coated or noncoated Ti-6A1-4V implant was inserted into both tibiae of 32 New Zealand White rabbits. Prior to implantation, the left tibia was contaminated with increasing concentrations of Staphylococcus aureus (10(2)-10(5) colony-forming units), ranging from very low (10(2)) to relatively high (10(5)). Four weeks after implantation, half of the tibial bone adjacent to the implant was harvested for bacteriological examination. Bacterial counts were quantified by plating serial dilutions. For the histological evaluation, sections of the implant with the remaining tibia were examined by semiquantitative scoring of infection parameters. The bacteriological data showed the inoculum dose and implant type to have a significant effect on the culture outcome: more bacteria were retrieved from the hydroxyapatite-coated implants than from the noncoated titanium implants. Histological evaluation showed an increased score for the infected left tibiae compared with their contralateral control. In addition, with increasing inoculum dosage, the difference between the two types of implant increased. We demonstrated that infections can occur with biocompatible, noncemented implants and that they are related to the dose of the original inoculum. Bacteria were more likely to grow onto or next to the hydroxyapatite implants than on titanium implants and resulted in a more severe histopathological characterization of infection.     

24-Hour motor activity after treatment with imipramine or fluvoxamine in major depressive disorder.

Psychomotor dysfunction in depression is related to alterations in the 24-h pattern of motor activity. After antidepressant treatment the diurnal pattern may be changed due to improvement of clinical state or pharmacological actions. The purpose of this study was to evaluate in 52 depressed in-patients the effects of imipramine (tricyclic antidepressant) and fluvoxamine (SSRI) on the 24-h motor activity. Motor activity was monitored by wrist-actigraphy during a medication-free period and after 4 weeks of treatment. Clinical improvement was not different after imipramine or fluvoxamine treatment. The Hamilton depression score decreased in patients treated with imipramine, as well as in patients treated with fluvoxamine. The clinical retardation score was also reduced in both treatment groups. However, patients treated with imipramine showed higher motor activity levels during the wake period in comparison to the medication-free period, and more fragmentation of motor activity during sleep. Treatment with fluvoxamine did not result in alterations in the 24-h pattern of motor activity. The improvement of depressive mood and retardation seems to play a minor role in the change of the pattern of motor activity after imipramine.     

Accumulation of the infectious virus and the viral antigen during the multiplication of the hepatitis A virus in an embryonic kidney cell culture of the rhesus macaque (FRhK-4)

Growth characteristics of the HAS-15 strain of human hepatitis A virus (HAV) in rhesus monkey foetal kidney cell line (FRhK-4) are described. The conditions optimal for the accumulation of infectious HAV and viral antigen (HAAg) in the infected cells and tissue culture fluids were studied. The production of infectious HAV occurred in the first stage while in the second stage predominantly HAAg was accumulating intracellularly. Serological properties of the cultivated HAV proved to be very similar to those of the HAV occurring in hepatitis A patients.     

Disability Management: Organizational Diversity and Dutch Employment Policy

Introduction While Human Resource Managers (HRM) and line managers could play a significant role in the prevention of job-related problems and in promotion of early job-continuation, it is not clear wether the chronically ill workers are recognized as a group. Unlike some other groups, distinguished by gender, age or ethnicity, those with chronic illness are less distinct and may not be included in diversity management programs. The aim of this research is to address theory and evidence in literature about the topic, as well as to inquire whether chronic illness of the employees is ‘visible’ in practice. Methods For desk research, we used a systematic search strategy involving medical, statistical, management, and social science databases (Web of Science, MedLine, Pub Med, Psych Info, etc.). Research results are based on case studies conducted with the managers and HRM of government and commercial organizations between March 2007 and October 2008 and between October 2008 and April 2009. These case studies were based on open interviews and focus group sessions (for human resource departments) which were consequently analyzed using thematical analysis. For group sessions, we used concept mapping to collect information from two groups of HRM professionals and managers. Secondary analysis included thematic and content analysis of ‘best practice’ organizations carried out by the Dutch organization Gatekeeper. Conclusions We have discovered that the chronically ill employees are largely invisible to HRM practitioners, line managers who do not always have the right instruments for implementation of the European or national frameworks. Most practitioners are unaware of the impact of chronic illness in their organizations and in employees work life.     

Lipid emulsions potently increase transgene expression in hepatocytes after adenoviral transfer.

Elimination of Kupffer cells by cytotoxic clodronate liposomes increases transgene expression in the liver after adenoviral transfer. Here, we demonstrate that empty l-alpha-phosphatidylcholine liposomes block uptake of vectors in the reticuloendothelial cells of the liver and increase human apolipoprotein (apo) A-I (approved gene symbol apo A-I) expression in C57BL/6 (1.3-fold) and Balb/c mice (3.1-fold) to the same extent as clodronate liposomes (1.5- and 3.4-fold, respectively). A similar elevation of human apo A-I levels was induced by the lipid emulsion Intralipid (1.5- and 2.8-fold in C57BL/6 and Balb/c mice, respectively). Not only Kupffer cells but also hepatic sinusoidal endothelial cells (HSEC) constitute the reticuloendothelial cells of the liver. The uptake of adenoviral vectors 1 h after transfer in C57BL/6 mice was 2.9-fold lower in Kupffer cells than in HSEC. In contrast, Kupffer cell uptake in Balb/c mice was 2.6-fold higher than in HSEC. Vector uptake in reticuloendothelial cells of the liver was reduced and transgene expression was increased in splenectomized and Rag2-deficient Balb/c mice but not in splenectomized and Rag1-deficient C57BL/6 mice. In conclusion, lipid emulsions for parenteral clinical use block uptake of adenoviral vectors by the reticuloendothelial cells of the liver and potently increase transgene expression.