The Cardiovascular Continuum extended: aging effects on the aorta and microvasculature

The 'Cardiovascular Continuum' was described by Dzau and colleagues in 2006 to explain the development over many years of coronary disease with its complications, then end-stage heart failure. The Continuum identified different points along the way where the process could be interrupted by drug therapies or interventions, then described the trials that have been undertaken over the last three decades to establish their value. The approach summarized the major steps in cardiology through modern times, but it had an emphasis on coronary atherosclerosis in prosperous nations, and did not account fully for the problems of aging, which occur in all societies. Aging of the aorta and elastic arteries causes arterial stiffening and leads to development of cardiac failure and microvascular disease in highly perfused organs such as the brain and kidneys. The 'Vascular Aging Continuum' which we introduce, dovetails with the late phases of the Cardiovascular Continuum and provides a more comprehensive explanation, especially for vascular diseases in nations with little atherosclerosis. It will become more common in the Western World where attention to risk factors and widespread use of statins are responsible for a decrease in atherosclerotic disease, prolongation of life, and dominance of macrovascular and microvascular arterial disease, as well as of cardiac failure.     

Therapeutic potential of endothelial progenitor cells in cardiovascular diseases

Endothelial dysfunction and cell loss are prominent features in cardiovascular disease. Endothelial progenitor cells (EPCs) originating from the bone marrow play a significant role in neovascularization of ischemic tissues and in re-endothelialization of injured blood vessels. Several studies have shown the therapeutic potential of EPC transplantation in rescue of tissue ischemia and in repair of blood vessels and bioengineering of prosthetic grafts. Recent small-scale trials have provided preliminary evidence of feasibility, safety, and efficacy in patients with myocardial and critical limb ischemia. However, several studies have shown that age and cardiovascular disease risk factors reduce the availability of circulating EPCs (CEPCs) and impair their function to varying degrees. In addition, the relative scarcity of CEPCs limits the ability to expand these cells in sufficient numbers for some therapeutic applications. Priority must be given to the development of strategies to enhance the number and improve the function of CEPCs. Furthermore, alternative sources of EPC such as chord blood need to be explored. Strategies for improvement of cell adhesion, survival, and prevention of cell senescence are also essential to ensure therapeutic viability. Genetic engineering of EPCs may be a useful approach to developing these cells into efficient therapeutic tools. In the clinical arena there is pressing need to standardize the protocols for isolation, culture, and therapeutic application of EPC. Large-scale multi-center randomized trials are required to evaluate the long-term safety and efficacy of EPC therapy. Despite these hurdles, the outlook for EPC-based therapy for cardiovascular disease is promising.     

软腭等离子射频打孔消融治疗阻塞性睡眠呼吸暂停综合征

目的：探讨等离子低温射频软腭打孔消融对阻塞性睡眠呼吸暂停低通气综合征的临床疗效。方法：对65例经多导睡眠图监测确诊为阻塞性睡眠呼吸暂停低通气综合征的患者行软腭等离子低温射频打孔消融术，缩短软腭及悬雍垂。结果：术后随访3～6个月，患者均取得了满意效果。患者射频治疗前和治疗12周后多导睡眠参数比较显示：治疗后Ⅰ Ⅱ期睡眠时间明显缩短，Ⅲ Ⅳ期睡眠时间明显延长，睡眠效率及最低脉氧饱和度(LSpO2)均显著提高(P＜0．05)；呼吸暂停低通气指数减低及打鼾时间缩短与治疗前相比差异非常显著(P＜0．01)。患者射频治疗12周后软腭长度及悬雍垂长度的缩短及鼾声评级的降低均较治疗前有显著差异(P＜0．01)。Epworth嗜睡程度评分亦较治疗前明显降低(P＜0．01)。结论：等离子低温射频软腭打孔消融对于轻度OSAHS患者具有较好的近期疗效，且方便、安全、微创、康复快，无不良反应，有较好的发展前景，值得推广应用。     

An initiative in mentoring to promote residents' and faculty members' careers.

Internal medicine trainees and faculty recognize the value of effective mentoring to help meet the personal and professional needs of residents. However, the paradigm of the mentor-trainee relationship is seriously threatened by increased clinical, research, and administrative demands on both faculty and housestaff. Moreover, the current criteria for promotion in most teaching hospitals emphasize scholarship, rather than citizenship, so activities such as mentoring devolve to a lower priority. In 2000, the Department of Medicine at Brigham and Women's/Faulkner Hospital initiated a program to improve the effectiveness of housestaff mentoring and recognize faculty contributions to resident career development. The authors report the feedback received from a survey of the 2002-03 medical housestaff (74% response rate) and describe their experiences with the initiation of this program. Over 90% of the housestaff respondents thought it important that the Department assigns an individual faculty mentor. In practice, time-consuming professional responsibilities made meetings difficult, but most pairs supplemented their interactions with e-mail. Discussions primarily focused on career advice and support. Housestaff thought mentors were helpful and available when needed. The department has established new metrics for recognizing faculty mentoring and now publicly rewards mentoring excellence. Of note, unassigned mentoring has increased since the initiation of this program. The authors conclude that the formal mentoring program has ensured that all trainees are provided with a mentor, which has facilitated faculty-housestaff interactions and increased recognition of faculty contributions to mentoring.     

Do men undergoing sterilizing cancer treatments have a fertile future?

This study was designed to assess the effect of cancer treatments on the natural and assisted reproductive potential of men. A cohort of men with cancer, in whom radiotherapy and/or chemotherapy was planned, were invited to participate. Twenty-two pre- and post-treatment semen samples were analysed. The reproductive potential of participants was assessed with respect to the current range of fertility treatment options available. Abnormal sperm concentrations were found in 27% of patients pre-treatment compared to 68% post-treatment following a mean latency of 20 months from treatment. Fifty-nine percent of patients experienced a clinically significant decrease in sperm, concentration following radiotherapy and/or chemotherapy; 23% developed azoospermia following treatment. Eighty-two percent of patients with testicular malignancy had oligo- or azoospermia post-treatment. Only one patient had a clinically significant reduction in the percentage of motile spermatozoa post-treatment. Cryopreservation of semen prior to treatment improved the fertility prospects of 55% of patients. Intracytoplasmic sperm injection (ICSI) enhanced the fertility prospects of a further 14%. In the absence of, or after depletion of, cryopreserved semen, ICSI could enhance the fertility prospects of 45% of patients. Fertilization has been achieved by ICSI using spermatozoa retrieved by testicular biopsy from an azoospermic testicular cancer survivor 8 years after chemotherapy. It was concluded that chemotherapy and/or radiotherapy may depress semen concentration to the extent of rendering a man infertile. The severity of the reduction in sperm concentration following treatment is unpredictable but likely to be most severe in those with testicular malignancy and those treated with radiotherapy or alkylating chemotherapy agents. Not all men are keen to undergo an appraisal of their post-treatment fertility potential, for reasons which are unclear. Improving awareness and education of patients concerning the effects of both cancer and cancer treatments on reproductive potential is essential. With the advent of ICSI, it is possible to offer a very reasonable chance of conception in all men with cancer who present for cryopreservation of semen prior to treatment in whom spermatozoa (even in very low concentrations) are present in the ejaculate.      

High-Throughput Genotyping with Single Nucleotide Polymorphisms

To make large-scale association studies a reality, automated high-throughput methods for genotyping with single-nucleotide polymorphisms (SNPs) are needed. We describe PCR conditions that permit the use of the TaqMan or 5' nuclease allelic discrimination assay for typing large numbers of individuals with any SNP and computational methods that allow genotypes to be assigned automatically. To demonstrate the utility of these methods, we typed >1600 individuals for a G-to-T transversion that results in a glutamate-to-aspartate substitution at position 298 in the endothelial nitric oxide synthase gene, and a G/C polymorphism (newly identified in our laboratory) in intron 8 of the 11-beta hydroxylase gene. The genotyping method is accurate-we estimate an error rate of fewer than 1 in 2000 genotypes, rapid-with five 96-well PCR machines, one fluorescent reader, and no automated pipetting, over one thousand genotypes can be generated by one person in one day, and flexible-a new SNP can be tested for association in less than one week. Indeed, large-scale genotyping has been accomplished for 23 other SNPs in 13 different genes using this method. In addition, we identified three "pseudo-SNPs" (WIAF1161, WIAF2566, and WIAF335) that are probably a result of duplication.