Occurrence of circulating 7-deoxyaglycone metabolites of 4′-deoxydoxorubicin in man

Summary In five cancer patients we have determined the pharmacokinetics of 4-deoxydoxorubicin (4-DOX), its alcoholic metabolite 4-deoxydoxorubicinol and the occurrence of circulating 7-deoxyaglycone metabolites. The 7-deoxyaglycone of the alcohol metabolite, the major aglycone of Adriamycin (ADR) present in man, was not detected in any serum sample. The 7-deoxyaglycone of the parent drug, which appears in concentrations in excess of 30ng/ml after ADR administration, was detected in only 2/5 patients in trace amounts. These preliminary data indicate a difference in biotransformation between ADR and 4-DOX despite their close structural similarities.     

Differences in diazepam pharmacokinetics in Chinese and white Caucasians – Relation to body lipid stores

Summary We have compared diazepam pharmacokinetics in 16 Chinese and 18 white Caucasian healthy male volunteers, resident in Hong Kong and have correlated them with physical attributes. Serum concentrations of diazepam and desmethyldiazepam were measured in venous blood by an enzyme-linked immunoassay (0–3 h samples) and HPLC (3–72 h samples). Pharmacokinetic parameters were derived assuming a two compartment model, distribution phase <6 h, and 100% oral systemic availability. Compared with the Chinese the white Caucasians were older, heavier, taller, and fatter, as judged by skin fold thickness (SFT) and total body weight to Ideal body weight (TBW/IBW) ratio; respective mean differences being 16%, 27%, 4%, 26%, and 15% (p<0.05). Mean diazepam apparent volume of distribution (V) and V/IBW were larger in the white Caucasians (52% & 39% respectively, p=0.002). SFT and TBW/IBW ratio yielded the best correlations with V, V/TBW and V/IBW (0.50–0.75, p<0.05). Obesity indices contributed most to the overall regressions (R² up to 0.52), and for V there was a further small effect (2%, partial F test) due to ethnic group, possibly reflecting stature. Mean peak diazepam concentration (C_max) was similar in both ethnic groups. Time to C_max (t_max) was more often prolonged in the Chinese (X ² test, p=0.01). Body fat and stature may thus account for these inter-ethnic differences in the apparent volume of distribution of diazepam, a highly lipid-soluble drug.     

Comparative effects ofβ 2-adrenoceptor agonists on intracranial self-stimulation,Sidman avoidance,and motor activity in rats

The effects of -adrenoceptor agonists were compared in various operant behavioral tasks, particularly intracranial self-stimulation (ICSS). Clenbuterol, salbutamol, and terbutaline all reduced responding by rats that lever-pressed for low stimulation intensities. The effects of clenbuterol in this test were completely reversed by propranolol, and those of salbutamol were partly reversed. Intermediate doses of clenbuterol and salbutamol slowed the initiation of rewarding brain stimulation in a shuttlebox but had little or no effect on the termination latencies. However, higher doses of both drugs lengthened the termination latencies. Motor activity was reduced at doses that attenuated ICSS responding. Complete tolerance occurred within 4 days to the effects of clenbuterol and salbutamol on leverpressing ICSS and to the effects of clenbuterol on motor activity. The apparent performance deficits induced by these drugs were overcome by more intense motivation. For example, even at high doses, clenbuterol reduced ICSS leverpressing only partially when animals bar-pressed for high rather than low stimulation intensities. Furthermore, all three drugs failed to alter Sidman avoidance responding at doses up to 100 times those that attenuated ICSS responding. It is concluded that although -adrenoceptor agonists cause apparent sedation in rats, this sedation is limited and shows rapid tolerance.     

医疗卫生机构气候韧性和环境可持续评价工具研究进展

目的 气候变化给医疗卫生机构带来诸多不确定性威胁,医疗卫生机构亟需提高自身的气候韧性并采取积极的应对措施,如何系统评价医疗卫生机构应对气候变化的能力成为应对气候变化挑战的工作重点。方法 使用范围综述筛选医疗卫生机构气候韧性和环境可持续评价工具相关文献和最新进展,并对密切相关的文献采用引文检索拓展研究范围。结果 借鉴国际经验已开发出适用于我国的《绿色医院建筑评价标准》,但对于医疗卫生机构气候韧性的指南和要求仍在探索中。国际上已经发展了三套较完整的工具包和指南,并已探索性开展了实地应用,包括加拿大的医疗卫生机构气候变化韧性工具包、美国的可持续和气候韧性医疗卫生机构工具包,以及世界卫生组织的气候韧性和环境可持续性的医疗卫生机构指南。结论 医疗卫生机构气候韧性和环境可持续能力评价工具构建是开展脆弱性评估和干预的基础,应积极借鉴国外相关经验开发适宜我国的评价工具,以增强机构和人员应对气候变化的能力。     

Health-related quality of life following percutaneous coronary intervention during the COVID-19 pandemic

Quality of Life Research - During the COVID-19 pandemic, widespread public health measures were implemented to control community transmission. The association between these measures and...     

Identification of geographic clusters for temporal heterogeneity with application to dengue surveillance

Identifying transmission of hot spots with temporal trends is important for reducing infectious disease propagation. Cluster analysis is a particularly useful tool to explore underlying stochastic processes between observations by grouping items into categories by their similarity. In a study of epidemic propagation, clustering geographic regions that have similar time series could help researchers track diffusion routes from a common source of an infectious disease. In this article, we propose a two-stage scan statistic to classify regions into various geographic clusters by their temporal heterogeneity. The proposed scan statistic is more flexible than traditional methods in that contiguous and nonproximate regions with similar temporal patterns can be identified simultaneously. A simulation study and data analysis for a dengue fever infection are also presented for illustration.     

Re: The limits of small-for-gestational-age as a high-risk category

European Journal of Epidemiology -