SCO‐101 (Endovion) was discontinued 20 years ago as a new drug under development against sickle cell anaemia. Data from the phase 1 studies remained unpublished. New data indicate that SCO‐101 might be efficacious as add‐on therapy in cancer. Thus, we report the results from the four phase 1 trials performed between 2001 and 2002. Adult volunteers received SCO‐101 or placebo in four independent trials. Adverse events were recorded, and SCO‐101 was determined for pharmacokinetic analysis. Ninety‐two volunteers completed the trials. The most remarkable adverse effect was a transient and dose‐dependent increase in unconjugated bilirubin. Plasma SCO‐101 elimination was approximately log linear, with apparent oral clearances of between 315 and 2103 mL/h for single doses, and between 121 and 2433 mL/h at steady state following oral administration. There was a marked decrease in clearance with increasing dose, and for repeated dose versus single dose. Tmax was greater, and Cmax and AUC∞ were lower in the fed state compared to the fasted state. Exposure was equivalent in males and females and for African Americans and Caucasians. In conclusion, SCO‐101 appears to be a safe drug with a predictable PK profile. Its efficacy as add‐on to standard anticancer drugs has yet to be defined. 相似文献
Journal of Assisted Reproduction and Genetics - To evaluate whether young women with idiopathic early ovarian aging, as defined by producing fewer oocytes than expected for a given age over... 相似文献
The objective of this study was to evaluate the potential of PEGylated 64Cu-liposomes in clinical diagnostic positron emission tomography (PET) imaging and PEGylated 177Lu-liposomes in internal tumor radiotherapy through in vivo characterization and dosimetric analysis in a human xenograft mouse model.
Methods
Liposomes with 5 and 10 mol% PEG were characterized with respect to size, charge, and 64Cu- and 177Lu-loading efficiency. The tumor imaging potential of 64Cu-loaded liposomes was evaluated in terms of in vivo biodistribution, tumor accumulation and tumor-to-muscle (T/M) ratios, using PET imaging. The potential of PEGylated liposomes for diagnostic and therapeutic applications was further evaluated through dosimetry analysis using OLINDA/EXM software. The 64Cu-liposomes were used as biological surrogates to estimate the organ and tumor kinetics of 177Lu-liposomes.
Results
High remote loading efficiency (>95 %) was obtained for both 64Cu and 177Lu radionuclides with PEGylated liposomes, and essentially no leakage of the encapsulated radionuclide was observed upon storage and after serum incubation for 24 h at 37 °C. The 10 mol% PEG liposomes showed higher tumor accumulation (6.2?±?0.2 %ID/g) than the 5 mol% PEG liposomes, as evaluated by PET imaging. The dosimetry analysis of the 64Cu-liposomes estimated an acceptable total effective dose of 3.3·10?2 mSv/MBq for diagnostic imaging in patients. A high absorbed tumor dose (114 mGy/MBq) was estimated for the potential radiotherapeutic 177Lu-liposomes.
Conclusion
The overall preclinical profile of PEGylated 64Cu-liposomes showed high potential as a new PET theranostic tracer for imaging in humans. Dosimetry results predicted that initial administered activity of 200 MBq of 64Cu-liposomes should be acceptable in patients. Work is in progress to validate the utility of PEGylated 64Cu-liposomes in a clinical research programme. The high absorbed tumor dose (114 mGy/MBq) estimated for 177Lu-liposomes and the preliminary dosimetric studies justify further therapeutic and dosimetry investigation of 177Lu-liposomes in animals before potential testing in man.
In this retrospective study
, we present the findings in 250 homicides by asphyxia in Denmark in a 25-year period, with a particular focus on the autopsy findings in strangulation. Our intention is for the results to be used in future death investigations, where difficulties in interpretation of findings in potential asphyxial deaths arise. Asphyxia homicides showed a strong bias with respect to sex, age, and homicide type. The frequent female victim was typically an adult, whereas the rarer male victim was most often a child. Female offenders most often killed their children, and male offenders most often killed their female partner. Generally, most asphyxia homicides took place in a domestic setting. Manual strangulation and ligature strangulation were the most common mechanisms of asphyxia homicides (81.6%). A lack of petechial hemorrhages, especially in the conjunctiva, was rare in homicidal strangulation, but there were exceptions, especially when there was postmortem decomposition, making it impossible to verify them. Most victims of strangulation had skin lesions in the face (including the jawline) or on the neck, with accompanying hemorrhages in muscle and connective tissue, but the findings could be subtle or compounded by decomposition. Fractures of the laryngo-hyoid complex were common in strangulation, particularly in manual strangulation (chi-sq = 4.0993, df = 1, P < 0.05) and were clearly related to the age of the victim (chi-sq = 82.193, df = 4, P < 0.001). In children and young adults dying from homicidal strangulation, a lack of fractures is to be expected, while a lack of fractures is unusual, but not entirely unexpected, for adults and aged people.
BackgroundSelf-management approaches are widely used to improve chronic care. In this context, health care professionals call for efficient tools to engage patients in managing their illness. Mobile health (mHealth), defined by WHO as medical and public health practice supported by mobile devices, is demonstrated to enhance self-management and health-coaching as an engaging tool in supporting behaviour change. Nevertheless, it is unclear how health-coaching and mHealth can benefit from each other.ObjectiveWe conducted a scoping review to provide a literature-overview and identify any existing gaps in knowledge of mHealth in combination with health-coaching interventions for improving self-management in patients with chronic diseases.Patient involvementNo patients were involved in the review process.MethodsThe five-stage framework by Arksey and O'Malley was used. The review surveys; PubMed, CINAHL, Embase, Scopus, and PsycInfo. Two independent reviewers performed review selection and characterization.ResultsThe review points at two approaches; (i) coaching used to support mHealth and (ii) mHealth as support for coaching. The findings suggest that patients prefer physical interactions to telecommunication. mHealth was primarily used to facilitate telecommunication and to monitor disease aspects.DiscussionWe found that mHealth and health-coaching interventions benefit from each other. The review report on a considerable unclarity in the coaching-methods and that the patients were more satisfied with physical interactions than mHealth. We suggest to prioritize human contact and to explore more personalized health technology.Practical valueThis scoping review can provide a framework for researchers and care providers to support discussion and introduction of new approaches and technology in self-management for patients with chronic diseases, thereby improving patients’ quality of life. 相似文献