Exploring the utility of whole‐exome sequencing as a diagnostic tool in a child with atypical episodic muscle weakness

The advent of whole‐exome next‐generation sequencing (WES) has been pivotal for the molecular characterization of Mendelian disease; however, the clinical applicability of WES has remained relatively unexplored. We describe our exploration of WES as a diagnostic tool in a 3½‐year old female patient with a 2‐year history of episodic muscle weakness and paroxysmal dystonia who presented following a previous extensive but unrevealing diagnostic work‐up. WES was performed on the proband and her two parents. Parental exome data was used to filter potential de novo genomic events in the proband and suspected variants were confirmed using di‐deoxy sequencing. WES revealed a de novo non‐synonymous mutation in exon 21 of the calcium channel gene CACNA1S that has been previously reported in a single patient as a rare cause of atypical hypokalemic periodic paralysis. This was unexpected, as the proband's original differential diagnosis had included hypokalemic periodic paralysis, but clinical and laboratory features were equivocal, and standard clinical molecular testing for hypokalemic periodic paralysis and related disorders was negative. This report highlights the potential diagnostic utility of WES in clinical practice, with implications for the approach to similar diagnostic dilemmas in the future.     

Syringe Exchange in the United States: A National Level Economic Evaluation of Hypothetical Increases in Investment

To examine whether increasing investment in needle/syringe exchange programs (NSPs) in the US would be cost-effective for HIV prevention, we modeled HIV incidence in hypothetical cases with higher NSP syringe supply than current levels, and estimated number of infections averted, cost per infection averted, treatment costs saved, and financial return on investment. We modified Pinkerton’s model, which was an adaptation of Kaplan’s simplified needle circulation theory model, to compare different syringe supply levels, account for syringes from non-NSP sources, and reflect reduction in syringe sharing and contamination. With an annual $10 to $50 million funding increase, 194–816 HIV infections would be averted (cost per infection averted $51,601–$61,302). Contrasted with HIV treatment cost savings alone, the rate of financial return on investment would be 7.58–6.38. Main and sensitivity analyses strongly suggest that it would be cost-saving for the US to invest in syringe exchange expansion.     

临床疑似TTP-HUS患者血浆置换治疗引起的并发症

由于采用血浆置换(PE)治疗血栓性血小板减少性紫癜溶血性尿毒综合征(TTP HUS)频率的增加,PE引起的并发症也成为制定治疗方案时需要考虑的因素。由于TTP HUS的诊断常常是不确定的,掌握PE治疗利弊之间的平衡已成为制定适当治疗方案的焦点。之前,我们于1996年～2002年间曾两次报道     

Abnormal expression of hepatoma specific gamma-glutamyl transferase and alteration of gamma-glutamyl transferase gene methylation status in patients with hepatocellular carcinoma

Abnormal expression of hepatoma specific gamma-glutamyl transferase and alteration of gamma-glutamyl transferase gene methylation status in patients with hepatocellular carcinoma@Jiang DR @Huang ZW @Lu JX @Tao QY @Yu JZ @Meng XY     

肝细胞生长因子诱导实验性视网膜脱离的病理机制研究

目的 观察肝细胞生长因子（HGF）对视网膜色素上皮（RPE）细胞屏障功能的影响以及RPE内过度表达HGF导致视网膜脱离（RD）的病理机制。 方法 编码HGF（AdCMV.HGF）、绿色荧光蛋白（Ad CMV.GFP）的E1/E3缺失的腺病毒载体，以5×10⁴ 噬斑形成单位（pfu）/眼注射到成年有色兔的视网膜下。检查注射后3、7、14、28 d时的眼底及组织病理变化,利用免疫组织化学和酶联免疫吸附试验（ELISA）方法检测HGF在视网膜和玻璃体的表达水平。 结果 对照组注射Ad CMV.GFP眼显示GFP几乎仅表达于PRE单核细胞层，AdCMV.HGF注射眼在注射点处的PRE细胞出现强的HGF免疫阳性反应。玻璃体内HGF的表达水平在注射7 d后达到最高峰、28 d后降低到基础水平。在HGF的表达期内AdCMV.HGF注射眼出现慢性RD和脉络膜慢性炎症。在RD区域，视网膜下的空间内可见增生性的RPE细胞，部分实验兔眼还产生多层的细胞膜结构。 结论 RPE内过度表达的HGF能引发慢性浆液性RD，同时伴有视网膜下RPE增生。提示HGF可能作为治疗RD的作用靶点。(中华眼底病杂志，2007，23：193-197)     

Incremental cost-effectiveness of two zidovudine regimens to prevent perinatal HIV transmission in the United States

BACKGROUND: Recently concluded clinical trials in Thailand have demonstrated that a short course of zidovudine therapy administered to human immunodeficiency virus-infected women during late pregnancy and labor can substantially reduce the likelihood of perinatal transmission of HIV. This regimen is both less expensive and less effective than the full course of therapy recommended for use in the United States by the U.S. Public Health Service (PHS). The objective of the current study is to estimate the incremental cost-effectiveness of the full-course zidovudine regimen in comparison to the short-course regimen that was tested in Thailand and to determine conditions under which the PHS-recommended regimen produces a net savings in societal resource utilization, relative to the shorter regimen. METHODS: We used standard methods of incremental cost-effectiveness analysis and derived cost and effectiveness estimates from published studies. The main outcome measure is the incremental cost-effectiveness ratio, which is the additional cost per additional case of perinatal HIV infection averted by the full course of therapy. RESULTS: Full-course zidovudine therapy costs an additional $21,337 per additional case of HIV infection averted, relative to the shorter regimen; this is much less than the cost of treating a case of pediatric HIV infection. CONCLUSIONS: Economic and clinical findings both favor full-course zidovudine therapy over short-course therapy to prevent perinatal transmission of HIV in the United States.     

Decision-Making in HIV Prevention Community Planning: An Integrative Review

Since 1994, the Centers for Disease Control and Prevention has required that the 65 health department grantees that receive funding for HIV prevention interventions engage in a community planning process to involve affected communities in local prevention decision making; to increase the use of epidemiological data to target HIV prevention resources; and to ensure that the planning process takes into account scientific information on the effectiveness and efficiency of different HIV interventions. Local community planning groups are charged with identifying and prioritizing unmet HIV prevention needs in their communities, as well as prioritizing prevention interventions designed to address these needs. Their recommendations, in turn, form the basis for the local health department's request for HIV prevention funding from the Centers for Disease Control and Prevention.Given the community planning process's central role in the allocation of federal HIV prevention funds, it is critical that sound decision-making procedures inform this process. In this article, we review the basics of the community planning prioritization process and summarize the decision-making experiences of community planning groups across the US. We then describe several priority-setting tools and decision analytic models that have been developed to assist in HIV community planning prioritization and discuss their strengths and weaknesses. Finally, we offer suggestions for improving the decision-analytic basis for HIV prevention community planning.