白介素与溃疡性结肠炎

近年来对白介素(interleukin,IL)和溃疡性结肠炎(ulcerative colitis,UC)的研究取得了很大进展,我们通过总结整理以前有关IL和UC的文献,概括出IL的产生和在UC发病及病理变化中的作用机制:IL-1直接介导了UC初期阶段炎症的发生:IL-8、IL-6直接促进炎性细胞过度分泌和/或抑制了炎性细胞的凋亡,IL-2分泌减少导致免疫系统内细胞间网络调节失衡, 使局部炎症介质和自由基释放,引起细胞毒作用,IL主要通过影响机体整体和/或局部免疫系统的功能介导UC的产生,并与UC的迁延难愈和反复发作有关．     

Comparison of the effects of acute and chronic beta-blockade on infarct size in the dog after circumflex occlusion

Summary In order to compare the effects of acute and chronic beta-blockade on infact size, the left circumflex coronary artery was occluded for 6 hours in 33 anesthetized dogs. The dogs (18 to 22 kg) were divided in to three groups; group 1 (N=10) served as controls, group 2 received intravenous nadolol (average dose 1.25 mg/kg) just prior to coronary occlusion, and group 3 received oral nadolol (80 mg) twice daily for 16 days prior to coronary occlusion. To ensure equivalent degrees of beta-blockade at the time of occlusion, group 2 and 3 dogs were given incremental doses of intravenous nadolol to abolish the chronotropic response to isoproterenol (2 /kg IV). Left ventricular pressure, its first derivative (dP/dt), and heart rate were monitored. The anatomic risk region was determined antemortem by Evan's blue staining while the infarct zone was delineated postmortem by tetrazoleum staining. Compared to Group 1, heart rate was 22% lower in group 2 and 15% lower in group 3 dogs 6 hours after occlusion (p<0.05). There were no differences among groups in peak left ventricular systolic pressure or mean arterial pressure. Infarct size as a function of the area at risk was 68±3% in group 1, 52±7% in group 2, and 44±8% in group 3. A significant difference was found only between groups 3 and 1. The data suggest that chronic beta-blockade provides greater protection against ischemic-induced necrosis than does acute beta-blockade. The greater protective effect of chronic beta-blockade may be due to chronic adaptive changes in either blood flow or metabolism.     

Prospective epidemiological study of the prevalence of human leukocyte antigen (HLA)‐B*5701 in HIV‐1‐infected UK subjects

Objectives

Human leukocyte antigen (HLA)‐B^*5701 is strongly associated with developing a hypersensitivity reaction to abacavir (ABC) in White and Hispanic subjects. Across the UK, limited data exist on HLA‐B^*5701 prevalence in HIV‐1‐infected subjects. We determined HLA‐B^*5701 prevalence in the general HIV‐1‐infected population and in specific ethnic groups, particularly Black Africans who, in general, exhibit greater genetic diversity. We also compared HLA‐B^*5701 results obtained from local laboratories with those from a central provider.

Design and methods

Multi‐centre, observational study. All HIV‐1‐infected adult individuals receiving care at participating centres were eligible, irrespective of treatment status or prior exposure to ABC. Subjects provided samples for HLA‐B^*5701 assessment by both local (blood) and central laboratories (buccal swabs). HLA‐B^*5701 prevalence was adjusted to represent the ethnic group composition of the general UK population, and by main ethnic group.

Results

From eight UK centres, 1494 subjects [618 (41%) White, 770 (52%) Black] were recruited. Eighty‐nine per cent of Black subjects reported an immediate country of origin in Africa. Overall adjusted HLA‐B^*5701 prevalence was 4.55% [95% confidence interval (CI) 3.49% to 5.60%]. Among White subjects, prevalence was 7.93% (CI 5.80% to 10.06%). Among Black subjects, only two (both Ugandan) were HLA‐B^*5701 positive giving a rate of 0.26% (CI 0.07% to 0.94%).

Conclusions

HLA‐B^*5701 prevalence was similar to previously reported rates in White HIV‐infected subjects but considerably lower than that reported in Black HIV‐1‐infected subjects, as a result of the large proportion of Black African subjects.     

肿瘤干细胞和抗肿瘤药物研发思路

目前有些抗肿瘤药物尽管有较好的近期疗效,然而肿瘤患者单纯依赖化疗通常难以达到长期生存的目的。本文试图从肿瘤干细胞理论解释抗肿瘤药物近期疗效和远期生存之间存在的矛盾,并探讨抗肿瘤药物的研究发展方向。     

Pharmacy workers’ perceptions and acceptance of bar-coded medication technology in a pediatric hospital

BackgroundThe safety benefits of bar-coded medication-dispensing and administration (BCMA) technology depend on its intended users favorably perceiving, accepting, and ultimately using the technology.Objectives(1) To describe pharmacy workers’ perceptions and acceptance of a recently implemented BCMA system and (2) to model the relationship between perceptions and acceptance of BCMA.MethodsPharmacists and pharmacy technicians at a Midwest U.S. pediatric hospital were surveyed following the hospital’s implementation of a BCMA system. Twenty-nine pharmacists' and 10 technicians’ self-reported perceptions and acceptance of the BCMA system were analyzed, supplemented by qualitative observational and free-response survey data. Perception-acceptance associations were analyzed using structural models.ResultsThe BCMA system’s perceived ease of use was rated low by pharmacists and moderate by pharmacy technicians. Both pharmacists and technicians perceived that the BCMA system was not useful for improving either personal job performance or patient care. Pharmacy workers perceived that individuals important to them encouraged BMCA use. Pharmacy workers generally intended to use BCMA but reported low satisfaction with the system. Perceptions explained 72% of the variance in intention to use BCMA and 79% of variance in satisfaction with BCMA.ConclusionsTo promote their acceptance and use, BCMA and other technologies must be better designed and integrated into the clinical work system. Key steps to achieving better design and integration include measuring clinicians’ acceptance and elucidating perceptions and other factors that shape acceptance.     

An investigation of the quality of breast cancer information provided on the internet by voluntary organisations in Great Britain

Objective

Patients increasingly use the internet to source health information. Voluntary organisations offering information and support often provide such information on their websites. However, the internet is unregulated and information can be of poor quality. The aim of this study was to evaluate the quality of breast cancer information provided by 10 Great Britain (GB) voluntary organisations’ websites.

Methods

Quality of websites was evaluated using an investigator-designed appraisal tool based on European Commission (EC) quality criteria for health-related websites. Completeness and transparency of breast cancer information, and usability of websites, were appraised.

Results

Typically, breast cancer-specific organisations provided the highest quality information, particularly in terms of its completeness. However, great variability in quality was identified. Areas of weakness related to transparency of information, in particular disclosure of authorship, and its apparent currency.

Conclusion

Voluntary organisations providing web-based breast cancer information have progress to make to ensure information provided is complete and transparent, and websites are user-friendly. Unfortunately, informed decision-making will not be optimised if patients cannot access quality information.

Practice implications

Voluntary organisations should regularly review the quality of information on their websites. Grading of websites allows healthcare professionals to identify and signpost patients to trustworthy, up-to-date websites. Thus, ensuring patients receive high quality information.     

Small heat-shock proteins interact with a flanking domain to suppress polyglutamine aggregation

Small heat-shock proteins (sHsps) are molecular chaperones that play an important protective role against cellular protein misfolding by interacting with partially unfolded proteins on their off-folding pathway, preventing their aggregation. Polyglutamine (polyQ) repeat expansion leads to the formation of fibrillar protein aggregates and neuronal cell death in nine diseases, including Huntington disease and the spinocerebellar ataxias (SCAs). There is evidence that sHsps have a role in suppression of polyQ-induced neurodegeneration; for example, the sHsp alphaB-crystallin (αB-c) has been identified as a suppressor of SCA3 toxicity in a Drosophila model. However, the molecular mechanism for this suppression is unknown. In this study we tested the ability of αB-c to suppress the aggregation of a polyQ protein. We found that αB-c does not inhibit the formation of SDS-insoluble polyQ fibrils. We further tested the effect of αB-c on the aggregation of ataxin-3, a polyQ protein that aggregates via a two-stage aggregation mechanism. The first stage involves association of the N-terminal Josephin domain followed by polyQ-mediated interactions and the formation of SDS-resistant mature fibrils. Our data show that αB-c potently inhibits the first stage of ataxin-3 aggregation; however, the second polyQ-dependent stage can still proceed. By using NMR spectroscopy, we have determined that αB-c interacts with an extensive region on the surface of the Josephin domain. These data provide an example of a domain/region flanking an amyloidogenic sequence that has a critical role in modulating aggregation of a polypeptide and plays a role in the interaction with molecular chaperones to prevent this aggregation.     

Italian healthcare workers' views on mandatory vaccination

Background  

Mandatory vaccination has contributed to the success of immunisation programmes but voluntary vaccination allows people to be responsible for their own health. There are benefits from both policies and the arguments between them remain subject to debate within and without the scientific community, both nationally and internationally. The aim of this study is to assess the opinions of those who actually work in the Vaccination Service.     

Acute (adult clinical inpatient) care nurses' attitudes towards and knowledge of nationally endorsed 5As smoking cessation guidelines

Nurses are expected to be involved in health promotion, including smoking cessation. This study aimed to assess nurses' knowledge, sense of responsibility and willingness to provide smoking cessation interventions as described in the national 5As guideline. Data were collected by a survey distributed to a convenience sample of nursing staff (n=162) from thirteen different adult acute care wards at a major metropolitan Melbourne hospital. Nearly all respondents (87%) agreed that they had a responsibility to counsel patients, and 22% were already doing so, but only 22% (n=36) of respondents demonstrated an adequate level of knowledge of smoking cessation. Nurses were more likely to counsel patients on health conditions related to their area of practice than those that were not. The findings indicate that greater emphasis is needed in undergraduate courses and in-service programs to increase nurses' awareness, and implementation of the 5As guideline for smoking cessation.