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811.
Hyvernat H Pulcini C Carles D Roques A Lucas P Hofman V Hofman P Bernardin G 《Scandinavian journal of infectious diseases》2007,39(2):183-185
We present 2 cases of community acquired S. aureus pneumonia carrying Panton Valentine leucocidin (PVL). These cases illustrate this clinical entity characterized by a younger and healthier population than usual staphylococcal pneumonias and complicated by a 75% mortality rate. We also discuss the diagnosis and therapeutic difficulties. 相似文献
812.
WST11, a novel generation of photo sensitizers to be used for vascular-targeted phototherapy (VTP), is effective at short interval between injection and illumination and it is expected to enable selective destruction of neovasculature with minimal side effects or skin photo toxicity. This study was conducted to evaluate the clinical and laboratory safety, tolerability and pharmacokinetic profile of WST11 given as a single intravenous administration (1.25, 2.5, 5, 7.5, 10, or 15 mg/kg) during an escalating dose study in healthy male subjects. This article describes WST11 population pharmacokinetic modeling and simulations performed to optimize the IV infusion-dosing regimen in combination with illumination, the target PK profile being plateau concentrations during approximately 30 min. The study included 42 healthy male subjects, administered 1.25, 2.5, 5, 7.5, 10, or 15 mg/kg as a 10-min IV infusion. A population pharmacokinetic model was developed using nonlinear mixed effects modeling (NONMEM). Monte Carlo simulations of the population PK dataset (NONMEM) were performed to select series of dosing regimen which would result in a plateau of concentration lasting at least 30 min and allow laser illumination. A two-compartment model with nonlinear elimination best described the data. No demographic factor was shown to affect the WST11 pharmacokinetics. The clearance was shown to decreases with the dose administered, ranging from 6 L/h (dose of 79 mg) to 2 L/h (dose of 1110 mg). The duration of the infusion was estimated at 12 min. The volume of distribution of the central compartment was 3 L and the volume of the peripheral compartment was 1.15 L. The apparent inter-compartmental clearance was 0.137 L/h. The between subjects variability on clearance and on volume was low. Residual variability was moderate with a CV of 21%. Due to the dose effect on clearance and the rapid elimination, simulations showed that different dosing inputs are necessary: for 5 and 10 mg/kg BW, a sufficiently good dosing scenario is to administer 80% of the dose over 5 min, 15% over 10 min and the remaining 5% over 10 min. For lower doses, the sequence 70% in 5 min/20% in 10 min/10% in 10 min is preferable. The pharmacokinetic profile of WST11 by IV administration would allow a treatment by laser illumination in good clinical conditions using controlled infusions. The study results do not indicate that the dose should be adjusted for body size. The only factor that determines the drug input profile is the dose level, since the elimination half-life decreases when the dose administered increases. The use of the population PK model for simulations has shown that, at dose level of 5 mg/kg or more, a loading dose of 80% dose given over 5 min followed by 15% of dose during 10 min and remained dose to give over 10 min would result in a favorable PK profile. 相似文献
813.
Veljko Nikolin Leticia Hatsue Sobreda Doi Michael Sieg Johannes Busch Denny Bttcher Laurence Tedeschi Amlie Poulard Vincent Staszewski Thomas Vahlenkamp Herve Poulet 《Viruses》2022,14(7)
Feline morbillivirus (FeMV) is a recently discovered virus belonging to the genus Morbillivirus of the virus family Paramyxoviridae. Often, the virus has been detected in urine of cats with a history of urinary disease and has a worldwide distribution. Currently, it is unclear which receptor the virus uses to enter the target cells. Furthermore, many aspects of FeMV biology in vivo, including tissue tropism, pathogenesis, and virus excretion in the natural host remain unclear. In this study we analyzed the replication of FeMV in various cell lines. Secondly, we tested if the presence of feline SLAMF1 (Signaling Lymphocytic Activation Molecule family 1/CD150, principal entry receptor for other members of the Morbillivirus genus) improved FeMV replication efficiency in vitro. Finally, to elucidate in vivo biology in cats, as a natural host for FeMV, we experimentally infected a group of cats and monitored clinical symptoms, viremia, and excretion of the virus during the course of 56 days. Our study showed that FeMV shares some features with other morbilliviruses like the use of the SLAMF1 receptor. For the first time, experimental infection of SPF cats showed that FeMV does not induce an acute clinical disease like other morbilliviruses but can induce lesions in the kidneys, including tubulointerstitial nephritis. Further investigations are needed to confirm the site and dynamics of replication of FeMV in the urinary tract and the longer-term impact of FeMV-induced lesions on the renal function. Whether FeMV infection can result in chronic kidney disease will require the monitoring of cats over a longer period. 相似文献
814.
Deborah Goldstein Nathan Ford Nicholas Kisyeri Maggie Munsamy Lirica Nishimoto Kufor Osi Herve Kambale Thomas Minior Moses Bateganya 《Journal of the International AIDS Society》2023,26(Z1):e26113
Introduction
Non-communicable diseases (NCDs) are highly prevalent in people living with HIV above 50 years of age and account for increasing mortality. There is little published evidence supporting person-centred, integrated models of HIV care, hypertension and diabetes treatment in southern Africa, and no data demonstrating mortality reduction. Where clinical visits for NCDs and HIV cannot be combined, integrated medication delivery presents an opportunity to streamline care and reduce patient costs. We present experiences of integrated HIV and NCD medication delivery in Eswatini and South Africa, focusing on programme successes and implementation challenges. Programmatic data from Eswatini's Community Health Commodities Distribution (CHCD) from April 2020 to December 2021 and South Africa's Central Chronic Medicines Dispensing and Distribution (CCMDD) from January 2016 to December 2021 were provided by programme managers and are summarized here.Discussion
Launched in 2020, Eswatini's CHCD provides over 28,000 people with and without HIV with integrated services, including HIV testing, CD4 cell count testing, antiretroviral therapy refills, viral load monitoring and pre-exposure prophylaxis alongside NCD services, including blood pressure and glucose monitoring and hypertension and diabetes medication refills. Communities designate neighbourhood care points and central gathering places for person-centred medication dispensing. This programme reported fewer missed medication refill appointments among clients in community settings compared to facility-based settings. South Africa's CCMDD utilizes decentralized drug distribution to provide medications for over 2.9 million people, including those living with HIV, hypertension and diabetes. CCMDD incorporates community-based pickup points, facility “fast lanes” and adherence clubs with public sector health facilities and private sector medication collection units. There are no out-of-pocket payments for medications or testing commodities. Wait-times for medication refills are lower at CCMDD sites than facility-based sites. Innovations to reduce stigma include uniformly labelled medication packages for NCD and HIV medications.Conclusions
Eswatini and South Africa demonstrate person-centred models for HIV and NCD integration through decentralized drug distribution. This approach adapts medication delivery to serve individual needs and decongest centralized health facilities while efficiently delivering NCD care. To bolster programme uptake, additional reporting of integrated decentralized drug distribution models should include HIV and NCD outcomes and mortality trends. 相似文献815.
Nick Verougstraete Annick Verhaeghe Jan Germonpré Herve Lebbinck Alain G. Verstraete 《Drug testing and analysis》2023,15(2):235-239
Etazene (or etodesnitazene) is a novel and highly active synthetic opioid belonging to the rapidly evolving and emerging group of “nitazenes.” Etazene metabolites were identified through analysis of a human urine sample. The sample was obtained from a 25-year-old man who attempted suicide by taking a new psychoactive substances (NPS) cocktail purchased online and was analyzed by ultrahigh performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). Etazene metabolites were predicted with BioTransformer 3.0, and the exact masses were added to the inclusion list. Eight possible metabolites were identified in the urine sample. N- and O-deethylation were identified as the predominant metabolism routes, resulting in M1 (O-deethylated etazene; most abundant metabolite based on the peak area), M2 (N-deethylated etazene), and M3 (N,O-dideethylated etazene) metabolites. Less abundant hydroxylated products of these deethylated metabolites and etazene were also found. Additionally, in the analysis without β-glucuronidase treatment, M1- and M3-glucuronide phase II metabolites were found. As N- and O-deethylated products seem to be the predominant urinary metabolites, the detection of these metabolites in urine can be useful to demonstrate etazene exposure. 相似文献
816.
817.
Astrid Boulenger de Hauteclocque Loïc Ferrer Damien Ambrosetti Solene Ricard Pierre Bigot Karim Bensalah François Henon Nicolas Doumerc Arnaud Méjean Virginie Verkarre Charles Dariane Stéphane Larré Cécile Champy Alexandre de La Taille Franck Bruyère Morgan Rouprêt Philippe Paparel Stéphane Droupy Alexis Fontenil Jean-Jacques Patard Xavier Durand Thibaut Waeckel Herve Lang Cédric Lebâcle Laurent Guy Geraldine Pignot Matthieu Durand Jean-Alexandre Long Thomas Charles Evanguelos Xylinas Romain Boissier Mokrane Yacoub Thierry Colin Jean-Christophe Bernhard 《BJU international》2023,132(2):160-169