The influence of liver dysfunction on cyclosporine pharmacokinetics -A comparison between 70 per cent hepatectomy and complete bile duct ligation in dogs-

The influence of experimentally induced hepatic dysfunction on the pharmacokinetics of Cyclosporine A (CsA) was determined in dogs. The pharmacokinetics of oral (PO) and intravenous (IV) CsA were studied before and after 70 per cent hepatectomy or complete bile duct ligation (CBDL). Changes in liver function were monitored by serial measurements of serum bilirubin, and by the maximum removal rate (Rmax) and plasma disappearance rate (ICG-K) of indocyanine green (ICG). Concentrations of CsA in whole blood were measured by HPLC. Seventy per cent hepatectomy caused significant liver dysfunction: the ICG-Rmax decreased by 47.7±7.1 per cent (mean±SD) and the ICG-K decreased by 61.3±9.7 per cent during the first week after hepatectomy. At the same time, the systemic clearance (CLs) of IV-CsA decreased by 43.9±8.2 per cent, the area under the concentration curve (AUC) of IV-CsA increased by 35.4±20.8 per cent and the bioavailability of CsA decreased by 26.4±14.8 per cent. CBDL also induced significant liver dysfunction: the ICG-Rmax decreased by 39.1±12.8 per cent and the ICG-K decreased by 65.6±3.6 per cent in the second week after the operation. During the same period, the AUC of PO-CsA decreased by 69.9±10.7 per cent and the bioavailability of CsA also decreased markedly by 73.9±15.6 per cent. These data indicate that hepatic impairment significantly influences the pharmacokinetics of CsA, not only by the changes in intestinal absorption, but also by those in hepatic, metabolism. Dose adjustment is therefore necessary in the presence of hepatic dysfunction in order to maintain an adequate blood concentration of CsA without causing side effects. © 1989 The Japan Surgical Society

Barriers in phase I cancer clinical trials referrals and enrollment: five-year experience at the Princess Margaret Hospital

BACKGROUND: There is a paucity of literature on the referral outcome of patients seen in phase I trial clinics in academic oncology centres. This study aims to provide information on the accrual rate and to identify obstacles in the recruitment process. METHODS: A retrospective chart review was performed for all new patients referred and seen in the phase I clinic at the Princess Margaret Hospital between January 2000 and June 2005. Data on their demographics, medical history, and details of trial participation or non-entry were recorded. RESULTS: A total of 667 new phase I referrals were seen during the stated period. Of these patients, 197 (29.5%) patients were enrolled into a phase I trial, and 64.5% of them started trial within 1 month of the initial visit. About a quarter (165 of 667) of the patients referred were deemed ineligible at their first visit, with the most frequent reasons for ineligibility being poor performance status, unacceptable bloodwork, too many prior treatments and rapid disease progression. The remaining 305 patients (45.7%) were potentially eligible at their initial visit, but never entered a phase I trial. The main reasons for their non-entry were patient refusal, other treatment recommended first, and lack of available trials or trial spots. CONCLUSION: This study provides information on the clinical realities underlying a referral to a phase I clinic and eventual trial enrollment. Better selection of patients, appropriate education of referring physicians, and opening phase I trials with fewer restrictions on some criteria such as prior therapy may enhance their recruitment rates

A secondary Fracture Prevention Programme to reduce fractures, hospital admissions, and mortality rates

Conference Theme: Happy Staff - Healthy People (開心員工 - 共建民康)published_or_final_versionThe Hospital Authority Convention, Hong Kong, 10-11 May 2010

Evaluation of the Osteoporosis Secondary Fracture Prevention Program at Queen Mary Hospital: successful recruitment is associated with lower re-fracture rate and mortality rate at one year

Conference Theme: Happy Staff - Healthy People (開心員工 - 共建民康)published_or_final_versionThe Hospital Authority Convention, Hong Kong, 10-11 May 2010

Understanding the attitudes of the elderly towards enrolment into cancer clinical trials

BACKGROUND: The optimal cancer treatment for an older population is largely unknown because of the low numbers of elderly patients accrued into clinical trials. This project focuses on the attitudes of the elderly about participation in clinical trials to determine if this is one of the barriers to the involvement of this population in clinical trials. METHODS: The first phase of this study was a self-administered questionnaire mailed to 425 elderly persons with cancer, selected from Princess Margaret Hospital oncology clinics. The second phase consisted of individual semi-structured interviews with cancer patients to assess their attitudes towards cancer, its management and enrolment into cancer clinical trials. RESULTS: Ninety-four patients responded to the survey giving a response rate of 22.1%. Three quarters of respondents stated that they would be willing to participate in a clinical trial. The factors that most influenced older patients' willingness to participate in a cancer study were recommendations from a cancer doctor and the chance that the study treatment may help them feel better. Seventeen survey responders participated in interviews. Common themes from these interviews included patient-physician communication, the referral process, and the role of age in cancer care decision-making. CONCLUSION: Most elderly people, who responded to this survey, are willing to consider participation in cancer clinical trials however, elderly patients do not appear to actively seek clinical trials and few were informed of the availability of clinical trials. Physician barriers and availability of appropriate clinical trials may play a bigger role in preventing accrual of elderly cancer patients into trials

Genetic-Background Modulation of Core and Variable Autistic-Like Symptoms in Fmr1 Knock-Out Mice

International audienc

Excursions into the Evolution of Early-Type Galaxies in Clusters

Recent observations have revealed that early-type galaxies (ETG) in clusters comprise an old galaxy population that is evolving passively. We review some recent observations from the ground and from HST that show that ETG have undergone a significant amount of luminosity evolution. This evolution is traced by two projections of the fundamental plane (FP): the size-magnitude relation (SMR) and the color-magnitude relation (CMR). We will briefly discuss the relevance of all these results in the context of the universality of the IMF.Comment: 10 pages, 2 figures, to appear in the proccedings of "New Quests in Stellar Astrophysics: The Link Between Stars and Cosmology, Chavez et al. ed

Clinical feasibility of (neo)adjuvant taxane-based chemotherapy in older patients: analysis of >4,500 patients from four German randomized breast cancer trials

Introduction Despite the fact that people older than 65 years of age have the highest incidence of developing breast cancer, these patients are excluded from clinical trials in most cases. Furthermore, most physicians tend towards therapy regimens without the use of dose-dense, highly active taxane-based treatments because of a lack of data regarding toxicities of these compounds in older patients. Methods Pooled side-effect data were analyzed from four prospective, randomized clinical trials in which patients of different age groups (60 years, between 60 and 64 years, and 64 years) with primary breast cancer received taxane-based chemotherapy. Results Dose delays, dose reductions, hospitalization, and therapy discontinuation increased with age. Hematologic toxicities and some nonhematologic toxicities were generally more common in older patients. Leucopenia increased from 55.3% in patients aged 60 years to 65.5% in patients aged 64 years (P<0.001), and neutropenia increased from 46.9% to 57.4% (P<0.001). There was no difference, however, in clinically more relevant febrile neutropenia between the different age groups. Thrombopenia shows a similar age-dependent increase, whereas there is no difference between the age groups concerning anemia. Hot flushes and elevated liver enzymes decreased with increasing age. Conclusions The present pooled analysis of a substantial cohort of older primary breast cancer patients demonstrates that taxane-containing (neo) adjuvant chemotherapy is feasible in older patients and that toxicity can be reduced by sequential therapy regimens

Nucleolar Association and Transcriptional Inhibition through 5S rDNA in Mammals

Changes in the spatial positioning of genes within the mammalian nucleus have been associated with transcriptional differences and thus have been hypothesized as a mode of regulation. In particular, the localization of genes to the nuclear and nucleolar peripheries is associated with transcriptional repression. However, the mechanistic basis, including the pertinent cis- elements, for such associations remains largely unknown. Here, we provide evidence that demonstrates a 119 bp 5S rDNA can influence nucleolar association in mammals. We found that integration of transgenes with 5S rDNA significantly increases the association of the host region with the nucleolus, and their degree of association correlates strongly with repression of a linked reporter gene. We further show that this mechanism may be functional in endogenous contexts: pseudogenes derived from 5S rDNA show biased conservation of their internal transcription factor binding sites and, in some cases, are frequently associated with the nucleolus. These results demonstrate that 5S rDNA sequence can significantly contribute to the positioning of a locus and suggest a novel, endogenous mechanism for nuclear organization in mammals

Mode shifting in school travel mode: examining the prevalence and correlates of active school transport in Ontario, Canada

<p>Abstract</p> <p>Background</p> <p>Studies examining the correlates of school transport commonly fail to make the distinction between morning and afternoon school trips. The purpose of this study was to examine the prevalence and correlates of mode shift from passive in the morning to active in the afternoon among elementary and secondary school students in Ontario, Canada.</p> <p>Methods</p> <p>Data were derived from the 2009 cycle of the Ontario Student Drug Use and Health Survey (OSDUHS). 3,633 students in grades 7 through 12 completed self-administered questionnaires. Socio-demographic, behavioural, psychological, and environmental predictors of active school transport (AST) were assessed using logistic regression.</p> <p>Results</p> <p>Overall, 47% and 38% of elementary school students reported AST to and from school, respectively. The corresponding figures were 23% and 32% for secondary school students. The prevalence of AST varied temporarily and spatially. There was a higher prevalence of walking/biking found for elementary school students than for secondary school students, and there was an approximate 10% increase in AST in the afternoon. Different correlates of active school transport were also found across elementary and secondary school students. For all ages, students living in urban areas, with a shorter travel time between home and school, and having some input to the decision making process, were more likely to walk to and from school.</p> <p>Conclusions</p> <p>Future research examining AST should continue to make the analytic distinction between the morning and afternoon trip, and control for the moderating effect of age and geography in predicting mode choice. In terms of practice, these variations highlight the need for school-specific travel plans rather than 'one size fits all' interventions in promoting active school transport.</p