对QT离散度实质的探讨

为探讨ＱＴ离散度（ＱＴｄ）的真实意义，观察１３９例急性心肌梗死（ＡＭＩ，ＡＭＩ组）及１０９例正常人（对照组）的最长ＱＴ间期（ＱＴｍａｘ）、校正ＱＴｍａｘ（ＱＴｃｍａｘ）及ＱＴｄ的变化。结果：①ＡＭＩ组的ＱＴｍａｘ、ＱＴｃｍａｘ和ＱＴｄ均显著高于对照组（分别为４２２．６０±３０．５１ｍｓｖｓ３８２．４６±２３．４０ｍｓ、４６０．２１±２８．９６ｍｓｖｓ３８８．５１±２０．１５ｍｓ、５９．８０±２８．４０ｍｓｖｓ３９．４３±１２．２１ｍｓ，Ｐ均＜０．００１）。②ＡＭＩ组中发生严重室性心律失常（ＶＡ）患者（１１４例）的ＱＴｍａｘ、ＱＴｃｍａｘ、ＱＴｄ与无ＶＡ的患者（２５例）相比，均有显著差异（分别为４４８．５８±３３．４０ｍｓｖｓ４１６．１０±３５．３０ｍｓ、４８１．４３±３５．１７ｍｓｖｓ４３９．６０±２７．１０ｍｓ、６６．９０±２０．７２ｍｓｖｓ４８．３２±２３．６１ｍｓ，Ｐ均＜０．００１）。认为ＡＭＩ时ＱＴｄ系Ｔ向量环在不同导联上的“投影”差异所引起的，其异常的本质是ＱＴ间期延长     

The folding pathway of alpha1-antitrypsin: avoiding the unavoidable

Understanding the folding pathway of α(1)-antitrypsin is of interest from both biomedical and fundamental molecular biology perspectives. The native fold of α(1)-antitrypsin is metastable, and therefore does not represent the most stable conformation that its primary sequence can adopt. More stable conformations are formed when the reactive center loop inserts, as the fourth strand, into the A β sheet. The accessibility of these alternative low-energy folds renders α(1)-antitrypsin susceptible to mutations that can result in dysfunction and pathology. Here, I review some of the literature from the past 20 years, which has examined how α(1)-antitrypsin folds and preserves its native metastable state. In addition, I look at the relationship between α(1)-antitrypsin folding and misfolding, and its role in disease.     

Perilipin deficiency and autosomal dominant partial lipodystrophy

Perilipin is the most abundant adipocyte-specific protein that coats lipid droplets, and it is required for optimal lipid incorporation and release from the droplet. We identified two heterozygous frameshift mutations in the perilipin gene (PLIN1) in three families with partial lipodystrophy, severe dyslipidemia, and insulin-resistant diabetes. Subcutaneous fat from the patients was characterized by smaller-than-normal adipocytes, macrophage infiltration, and fibrosis. In contrast to wild-type perilipin, mutant forms of the protein failed to increase triglyceride accumulation when expressed heterologously in preadipocytes. These findings define a novel dominant form of inherited lipodystrophy and highlight the serious metabolic consequences of a primary defect in the formation of lipid droplets in adipose tissue.     

Pharmaco-economic issues for diabetes therapy

A systematic review was undertaken to analyse pharmaco-economic issues in diabetes, with evidence selected on the basis of relevance and immediacy. Pharmaco-economics in diabetes primarily relates to making choices about antidiabetic pharmaceuticals, and this is being influenced by global trends. Trends include increasing numbers of patients with diabetes, with increasing costs of caring for people with diabetes, and an ever-present focus on the costs of pharmaceuticals which are predicted to increase as the pace of development of new medications parallels the increasing incidence of the condition. These developments have influenced the demand for health care in diabetes in the last decade, and will continue to determine this in the coming decade. Recent national experiences are cited to illustrate current issues and to focus specifically upon the challenges facing a raft of new diabetes treatment options now hitting the marketplace, although supported by fewer completed long-term trials. It can be anticipated that these newer agents will be appraised for their cost-effectiveness or value for money. Economic analyses for some of the new technologies are summarized; in general, the peer-reviewed publications using well-accepted and validated models have reported that these technologies are cost-effective. Endorsement of any technology in a national setting is not awarded simply because the incremental cost-effectiveness ratio (ICER) falls below the threshold regarded as value for money. In most national observations the reviewers expressed concerns about assumptions used in economic modelling which resulted in the ICERs being deemed optimistic at best, generally highly uncertain, and resulting in the cost-effectiveness appearing better than it really would be in clinical practice. This has often led to the authorities concluding that the price advantage of new technologies over comparators could not be justified, essentially leading to restrictions in use compared to their licence. In general, a paucity of robust evidence on longer-term outcome data together with a lack of health-related quality of life (HRQOL) data collected in a reliable manner in appropriate patients and amenable to utility (and hence quality adjusted life year or QALY) estimation have resulted in problems for these new drugs at the so-called fourth (cost-effectiveness) hurdle. In the light of these findings, the implications for generating credible fit-for-purpose cost-effectiveness analyses of new technologies in diabetes are discussed. Throughout this chapter, the interested reader is referred to a number of excellent review articles for further details.     

Hypocupremia associated with prior vitamin B12 deficiency

Clinical similarities between vitamin B(12) and copper deficiencies prompted us to investigate if hypocupremia is present in patients receiving vitamin B(12) supplementation. Our pilot study results indicate that a significant number of elderly patients with prior diagnosis of vitamin B(12) deficiency have also undiagnosed hypocupremia.     

The prognostic value of health-related quality-of-life data in predicting survival in glioblastoma cancer patients: results from an international randomised phase III EORTC Brain Tumour and Radiation Oncology Groups, and NCIC Clinical Trials Group study

This is one of the few studies that have explored the value of baseline symptoms and health-related quality of life (HRQOL) in predicting survival in brain cancer patients. Baseline HRQOL scores (from the EORTC QLQ-C30 and the Brain Cancer Module (BN 20)) were examined in 490 newly diagnosed glioblastoma cancer patients for the relationship with overall survival by using Cox proportional hazards regression models. Refined techniques as the bootstrap re-sampling procedure and the computation of C-indexes and R(2)-coefficients were used to try and validate the model. Classical analysis controlled for major clinical prognostic factors selected cognitive functioning (P=0.0001), global health status (P=0.0055) and social functioning (P<0.0001) as statistically significant prognostic factors of survival. However, several issues question the validity of these findings. C-indexes and R(2)-coefficients, which are measures of the predictive ability of the models, did not exhibit major improvements when adding selected or all HRQOL scores to clinical factors. While classical techniques lead to positive results, more refined analyses suggest that baseline HRQOL scores add relatively little to clinical factors to predict survival. These results may have implications for future use of HRQOL as a prognostic factor in cancer patients.