Short-term selection for acute ethanol tolerance and sensitization from an F2 population derived from the high and low alcohol-sensitive selectively bred rat lines.

Previous studies have identified quantitative trait loci (QTL) in the inbred high and low alcohol-sensitive rat (IHAS1 and ILAS1) strains. The original development of the strains involved selection for ethanol sensitivity based on duration of the loss of the righting reflex (LORR) after a standard dose of ethanol. This paper confirms some of these QTL using a short-term selection procedure based on the difference between the blood ethanol level at LORR and regain of the righting response. An F(2) population of rats was developed by a reciprocal cross of IHAS1 and ILAS1 rats. Selection for five generations was carried out using delta-blood ethanol concentration (dBEC) as the selection trait, where dBEC=BECLR (BEC at loss of righting reflex)-BECRR (BEC at regain of righting reflex). The lines were labeled tolerant (TOL) or sensitive (SENS). Approximately one-third of the offspring for each generation in each line were genotyped using DNA markers that had been previously found to be linked to QTL on chromosomes 1, 2, 5, 12, and 13. By the fifth generation of selection, the lines showed a very large difference in dBEC, BECRR, and duration of LORR; BECLR showed little segregation during the selection, and latency to lose the righting reflex showed none. IHAS allele frequency increased in the SENS line for markers on chromosomes 1, 5, 12, and 13 while ILAS allele frequency increased in the TOL line. These results were in good agreement with the two previous QTL studies. On chromosome 2, the selection resulted in an accumulation of ILAS alleles in both lines. This study provides independent confirmation of the location of QTL on chromosomes 1, 5, 12, and 13 for ethanol sensitivity. It also suggests that genetic differences in duration of LORR are mediated primarily by the dBEC phenotype.     

Resuscitation at the limits of viability – an Irish perspective

Background:  Advances in neonatal care continue to lower the limit of viability. Decision making in this grey zone remains a challenging process.
Objective:  To explore the opinions of healthcare providers on resuscitation and outcome in the less than 28-week preterm newborn.
Design/Methods:  An anonymous postal questionnaire was sent to health care providers working in maternity units in the Republic of Ireland. Questions related to neonatal management of the extreme preterm infant, and estimated survival and long-term outcome.
Results:  The response rate was 55% (74% obstetricians and 70% neonatologists). Less than 1% would advocate resuscitation at 22 weeks, 10% of health care providers advocate resuscitation at 23 weeks gestation, 80% of all health care providers would resuscitate at 24 weeks gestation. 20% of all health care providers would advocate cessation of resuscitation efforts on 22–25 weeks gestation at 5 min of age. 65% of Neonatologists and 54% trainees in Paediatrics would cease resuscitation at 10 min of age. Obstetricians were more pessimistic about survival and long term outcome in newborns delivered between 23 and 27 weeks when compared with neonatologists. This difference was also observed in trainees in paediatrics and obstetrics.
Conclusion:  Neonatologists, trainees in paediatrics and neonatal nurses are generally more optimistic about outcome than their counterparts in obstetrical care and this is reflected in a greater willingness to provide resuscitation efforts at the limits of viability.     

Digital clubbing: finally, a gene

Mutations in 15-hydroxyprostaglandin dehydrogenase cause primary hypertrophic osteoarthropathy
Uppal et al. (2008)
Nature Genetics 40 (6): 789–793     

假白血病淋巴瘤细胞系

白血病淋巴瘤细胞系是生物医学领域最重要的研究工具之一.然而,近年来的多项研究显示相当数量的人白血病淋巴瘤细胞系为假细胞系或身份不正确.假白血病淋巴瘤细胞系可分为三种类型.第一种是完全的假细胞系,交叉污染发生于细胞系的早期建系阶段,并迅速被具有增殖优势的其他细胞系取代.第二种是身份错误的假细胞系,交叉污染发生于建系后,而真正的原型细胞系可能存在.最后一种是非恶性细胞系.本文对近年来发现的各种假白血病淋巴瘤细胞系作一综述.     

Improving delivery of preventive health care with the comprehensive annotated reminder tool (CART).

OBJECTIVES: We assessed the effect of the Comprehensive Annotated Reminder Tool (CART) on physician adherence to preventive services recommendations. STUDY DESIGN: Using a randomized pretest/posttest control group design, we assigned physicians to the CART group or the control group, followed up prospectively, and evaluated for appropriate adherence to guidelines. The 3 age-specific versions of the CART annotated history and physical examination form contained up to 49 preventive services recommendations. POPULATION: All resident physicians in a large family practice residency program were studied over the course of 1 academic year. OUTCOMES MEASURED: We performed blinded chart reviews to assess the appropriateness of preventive services ordered by the physicians before the introduction of the CART, during its use, and after its removal. A multiple-choice test completed before and after the use of the CART forms assessed knowledge. RESULTS: When the CART was used, the appropriateness of physician preventive behavior increased by 21% overall. The appropriateness of history, physical examination, and laboratory interventions increased by 33%. When the CART was removed, physician behavior returned to baseline (P < or = .0025 for 16 of 20 interventions). No significant differences were observed in the control group over time. Knowledge increased over the study period for all physicians (P < or = .005) but did not differ significantly between the treatment and control groups (P = .608). CONCLUSIONS: Use of the CART significantly improved physician performance in the appropriate delivery of preventive care.     

Recommendations for the use of etanercept in psoriasis: a European dermatology expert group consensus

BACKGROUND: Psoriasis is a chronic, inflammatory skin disorder that has a significant impact on quality of life and, particularly in moderate to severe cases, adversely affects the patient's overall health and well-being. Biological treatments, such as etanercept, are being widely adopted across Europe for treatment of moderate to severe psoriasis due to favourable safety and efficacy profiles. The increase in usage, combined with a growing body of clinical evidence, has identified a need to clarify the best use of etanercept within its current treatment label. OBJECTIVE: To prepare a series of recommendations agreed by an expert group of dermatologists, relating to the most effective use of etanercept for psoriasis in Europe, within the product license. METHODS: An expert panel of dermatologists from across Europe completed a Delphi survey to address the current use of etanercept in psoriasis in Europe. In June 2005 the results were presented to the expert panel at their nominal group meeting, and a consensus was agreed. RESULTS: It was recommended that, where possible, patients are initiated on the 50 mg twice-weekly (BIW) dose. Etanercept should be given until remission is achieved (maximum 24 weeks) and retreatment should be initiated according to the physician's judgement. Before commencing treatment, contraindications, such as infection or previous malignancy (within 5 years), should be ruled out. CONCLUSIONS: The consensus presented herein provides valuable clarification of use of etanercept according to the label, which may have wider implications relating to the use of all biological therapies in psoriasis.