家族性高胆固醇血症的心血管超声研究

目的(1)研究家族性高胆固醇血症(FH)血管超声表现;(2)研究FH的超声心动图表现并分析冠状动脉血流储备(CFVR)的变化。方法经我院动脉粥样硬化研究室确诊的FH患者27例。其中男12例,女15例,年龄3.7~37岁,平均16岁。采用彩色多普勒超声显像仪观察颈总动脉内中膜厚度(IMT)、管腔狭窄程度等改变。并观察心脏、瓣膜、主动脉的形态结构和功能。冠状动脉血流显像测量前降支(LAD)远端静息状态和经静脉注射腺苷[140μg/(kg·min)]3min时舒张期平均血流速度并计算冠状动脉血流储备(CFVR);观察静息状态和腺苷负荷试验[140μg/(kg·min)]6min时室壁运动。结果27例患者血清总胆固醇(CT)均明显增高,25例患者皮肤有黄色瘤,21例以黄色瘤为首发表现。18例患者颈总动脉IMT有不同程度的增厚,平均(1.44±0.25)mm。6例患者颈总动脉有斑块形成,直径狭窄率平均为(44.67±5.16)%。患者心脏收缩和舒张功能基本正常,主动脉瓣反流10例,主动脉瓣膜狭窄3例,主动脉瓣上狭窄7例。二尖瓣反流14例。5例负荷试验阳性。16例CFVR≤3.0,其中11例CFVR≤2.0。结论FH是一组特殊人群,以发病年龄早,并以心血管系统受累为主要表现。超声能提供FH患者动脉粥样硬化的形态和功能变化的重要依据。     

The Detection of Heterozygous Familial Hypercholesterolemia in Ireland

Heterozygous familial hypercholesterolemia (HeFH) is an autosomal dominant condition with a population prevalence of 1 in 500, and is associated with significant cardiovascular morbidity and mortality. It may be caused by mutations in the low-density lipoprotein (LDL) receptor, apolipoprotein B100 (Apo B100), or proprotein convertase subtilisin/kexin type 9 (PCSK9) genes, with over 1,000 causative mutations described. Statin therapy in HeFH is considered effective and safe. Audit data suggest that approximately 80% of the putative HeFH population remains unidentified and, therefore, there is a need to develop a strategy for the identification of affected individuals so that early lipid-lowering treatment may be offered. There is good evidence showing the effectiveness and acceptability of HeFH screening programs in Europe. The authors describe a protocol for an all island approach to HeFH detection in the Republic of Ireland/Northern Ireland. Index cases will be identified by opportunistic screening using the Simon Broome, or Make Early Diagnosis to Prevent Early Death (MedPed) and World Health Organization (WHO) criteria. Patients identified as "definite," "probable," or "possible" HeFH criteria will be offered genetic testing. The authors expect causative mutations to be identified in approximately 80% of patients with "definite" HeFH but in only approximately 20% of patients with "possible" HeFH. Cascade screening will be undertaken in first-degree relatives of the index case using genetic testing (where a causative mutation has been identified), or otherwise using LDL cholesterol concentration. The establishment of a HeFH screening program on an all-island basis will require: expansion of the existing molecular genetics diagnostic services, the establishment of a cohort of nurses/genetic counselors, a HeFH database to support cascade testing, the development of a network of lipid clinics (in a primary or secondary care setting), and an educational initiative to raise awareness of HeFH among healthcare professionals and the general population.     

Evaluation of Coronary Flow Velocity Reserve in Homozygous Familial Hypercholesterolemia by Transthoracic Doppler Echocardiography and Dual-Source Computed Tomography

Homozygous familial hypercholesterolemia (HoFH) is a rare disorder characterized by the early onset of atherosclerosis and usually occurs at the ostia of coronary arteries. In this study, we used transthoracic Doppler echocardiography (TTDE) to evaluate the dynamic changes of coronary flow in HoFH patients and to detect aortic and coronary atherosclerosis by dual-source computed tomography (DSCT). We studied 20 HoFH patients (12 females, 8 males, mean age 13.1 ± 5.3 years, with a mean low density lipoprotein (LDL) cholesterol of 583 ± 113 mg/dL) and 15 control patients (8 females, 7 males, mean age 15.2 ± 6.9 years, with a mean LDL cholesterol 128 ± 71 mg/dL) using TTDE and DSCT. None of the patients showed evidence of ischemia with standard exercise testing. Though the baseline coronary flow was similar between HoFH patients and normal controls, the hyperemic flow velocities and, thus, the coronary flow velocity reserve (CFVR) were significantly lower in those with HoFH. All HoFH patients had aortic plaques, nine of them with the coronary artery ostia simultaneously, who had significantly higher LDL-cholesterol and lower CFVR than those without ostia plaques. Our data demonstrated that TTDE together with DSCT could be a useful noninvasive method for detection of coronary flow dynamics and atherosclerosis specifically in HoFH subjects with coronary ostia. (E-mail: lizhian_anzhen@yahoo.com.cn)     

Optimizing Diet,Weight, and Exercise in Adults With Familial Hypercholesterolemia

Familial hypercholesterolemia results in severe elevation of low-density lipoprotein-cholesterol (LDL-c) and is estimated to affect up to 1 in 250 Americans. The rise in LDL-c has implications for the development of atherosclerotic disease and premature death. Treatment starts by its early identification, with careful attention to family history, physical exam, and laboratory analysis. By identifying this disorder, the nurse practitioner can assist the patient in implementing lifestyle changes involving exercise, weight loss, and diet, each impacting LDL-c. For those with familial hypercholesterolemia, each 1% reduction in LDL-c translates to a 3% risk reduction in the development of coronary artery disease.     

Familial hypercholesterolemia: current treatment and advances in management

Heterozygous familial hypercholesterolemia is associated with elevated levels of LDL-cholesterol and the development of premature cardiovascular disease. The condition is considerably under-diagnosed and under-treated. Statins are the first choice treatment for all patients with heterozygous familial hypercholesterolemia. For those patients who do not reach their treatment target or who are unable to use adequate statin dose, several alternative treatment modalities can be used, either as add-on therapy or as monotherapy. In this review the various treatment options are discussed.     

Efficacy and Safety of Ezetimibe and Rosuvastatin Combination Therapy Versus Those of Rosuvastatin Monotherapy in Patients With Primary Hypercholesterolemia

Purpose

The aim of this study was to evaluate the safety and efficacy of combination treatment of rosuvastatin with ezetimibe in patients with primary hypercholesterolemia.

原发性高胆固醇血症血管内皮依赖性舒张功能失调的无创性检测

采用无创性高分辨超声技术，检测了１７例无症状的原发性高胆固醇血症患者和１７例血浆胆固醇水平正常的对照者在基础状态下，反应性充血及含服硝酸甘油后肱动脉的内径变化。结果显示，前者血流介导性肱动脉舒张较正常组明显减弱（５．９％±２．３％比１４．５％±３．４％，Ｐ＜０．００１）；血流介导性肱动脉舒张与血总胆固醇（ＴＣ）及低密度脂蛋白胆固醇（ＬＤＬ－Ｃ）呈显著负相关（相关系数ｒ分别为－０．６４２及－０．６２３，Ｐ＜０．００１）；而两组对硝酸甘油的反应差异无显著性（２４．５％±４．３％比２３．０％±７．０％，Ｐ＝０．４９）。结果表明，原发性高胆固醇血症患者血管内皮依赖性舒张功能明显受损，ＬＤＬ－Ｃ升高是内皮依赖性舒张功能障碍主要的独立危险的因素。     

Familial hypercholesterolemia presenting with multiple nodules of the hands and elbow

Familial hypercholesterolemia (FH) is a common but commonly missed diagnosis. Tendon xanthomas are a physical sign strongly suggestive of FH. Physicians must identify tendon xanthomas, apply validated clinical scoring such as the Dutch Lipid Clinic Network criteria and offer cascade screening. This approach will increase recognition of FH.     

纯合型家族性高胆固醇血症诊疗进展

家族性高胆固醇血症(familial hypercholesterolemia,FH)是严重遗传代谢性疾病,临床上分为纯合和杂合两种类型,纯合型FH(homozygous FH,HoFH)发病率为1/(16万~100万),被认为是罕见病。HoFH主要特点为极高水平的低密度脂蛋白胆固醇、多部位黄色瘤及早发动脉粥样硬化性心血管疾病,如不及时诊断、早期治疗, 青少年期即可发生心肌梗死甚至死亡。近年来,国际上也越来越重视FH的早期诊断和治疗,发布了多项FH指南与共识,我国亦结合国情制定了适合中国人的筛查诊断标准,为更好治疗FH提供了基础。本文就HoFH现有的诊断标准、鉴别诊断筛查和治疗方法进行综述,旨在提高医生对该病的认识。     

Screening methods in the diagnosis and assessment of children and adolescents with familial hypercholesterolemia

Familial hypercholesterolemia is an autosomal dominant disorder. Heterozygous familial hypercholesterolemia (FH) has an estimated incidence of 1 per 300–500 births and is characterized by increased serum total- and low-density lipoprotein-cholesterol levels and an increased risk of coronary heart disease. Early diagnosis and cholesterol-lowering treatment are essential to prevent premature coronary heart disease. Effective screening strategies are therefore of great importance. Screening can be done as selective or general population screening. There is no generally accepted screening program for FH in children and adolescents. In The Netherlands a systematic genetic family cascade screening program has been going on since 1994. In most countries there is no systematic screening for the disease, but clinical and genetic family cascade screening has been applied. Selective screening programs have failed to identify a large number of FH cases. Recommendations for general pediatric population screening have therefore emerged. Controversy exists as to which approach should be adopted. Family cascade screening has been estimated to be the most cost-effective screening method. No general pediatric screening program has been tested on a larger scale, validated or subjected to cost–benefit analyses.     

Colesevelam hydrochloride in the management of dyslipidemia

Dyslipidemia is a highly heterogeneous group of disorders strongly influenced by both genetic and environmental factors. Dyslipidemia significantly increases risk for atherosclerotic disease and all of its various clinical manifestations. Identifying patients with dyslipidemia and initiating therapies aimed at normalizing the lipid profile has been demonstrated to significantly reduce the risk for myocardial infarction, stroke and cardiovascular mortality in both the primary and secondary prevention settings. Guidelines in Europe, Canada and the USA emphasize the need to reduce the burden of atherogenic lipoproteins in serum and to raise levels of high-density lipoproteins in patients at risk for cardiovascular events. Statins have emerged as front-line therapy for managing dyslipidemia, especially in patients with elevated serum levels of low-density lipoprotein cholesterol. As guidelines emphasize the need to reduce serum low-density lipoprotein cholesterol to lower levels, goal attainment can be challenging. The use of combination therapy increases the likelihood of therapeutic success for many patients. Furthermore, a significant percentage of patients with dyslipidemia either cannot achieve goals on statin monotherapy, choose not to take a statin or do not tolerate these drugs due to adverse side effects, such as myalgias, weakness or hepatotoxicity. This article summarizes the pharmacology, clinical efficacy and safety of colesevelam hydrochloride, a bile acid-binding resin. Bile acid-binding resins are orally administered anion-exchange resins that are not absorbed systemically. These agents bind bile acids and reduce their reabsorption at the level of the terminal ileum and prevent their enterohepatic recirculation. Colesevelam has a favorable side effect and toxicity profile and significantly impacts serum levels of lipoproteins when used as monotherapy or when used in combination with either statins or ezetimibe.     

Efficacy of Lomitapide in the Treatment of Familial Homozygous Hypercholesterolemia: Results of a Real-World Clinical Experience in Italy

Introduction

Homozygous familial hypercholesterolaemia (HoFH) is a rare form of inherited dyslipidemia resistant to conventional cholesterol-lowering medications so that lipoprotein apheresis (LA) is usually required. Lomitapide has been approved for the treatment of HoFH. The aim of this study was to evaluate the benefits of lomitapide in HoFH patients followed with the usual clinical care.

Methods

Clinical and biochemical data were retrospectively collected in 15 HoFH patients (10 with mutations in the LDLR gene and 5 in the LDLRAP1 gene) treated for at least 6 months with lomitapide in addition to lipid-lowering therapies (LLT) in different Lipid Clinics across Italy.

Results

The mean follow-up period was 32.3 ± 29.7 months. During background therapies, HoFH patients showed a mean LDL-C level of 426.0 ± 204.0 mg/dl. The addition of lomitapide at the average dosage of 19 mg/day lowered LDL-C levels by 68.2 ± 24.8%. At their last visit, 60% of patients showed LDL-C <100 mg/dl and 46.6% <70 mg/dl. During follow-up, 8 of 10 patients receiving LA (80%) stopped this treatment due to marked LDL-C reduction. A wide range (13–95%) of individual LDL-C reduction was observed, but this was not related to genotype. During follow-up, 53.3% of patients reported at least one episode of diarrhea, but none was referred as severe; none had liver transaminase >5× ULN or had to stop treatment due to side effects. A subset of patients was evaluated by liver ultrasound and fibroscan (n = 5) or nuclear magnetic resonance with spectroscopy (MRS) (n = 1) not showing clinical evidence of liver damage.

Conclusion

In this real-world experience, lomitapide was confirmed to be a very powerful cholesterol-lowering agent in HoFH showing a good safety profile.

     

A Phase III,Multicenter, Randomized,Double-blind,Active Comparator Clinical Trial to Compare the Efficacy and Safety of Combination Therapy With Ezetimibe and Rosuvastatin Versus Rosuvastatin Monotherapy in Patients With Hypercholesterolemia: I-ROSETTE (Ildong Rosuvastatin & Ezetimibe for Hypercholesterolemia) Randomized Controlled Trial

Purpose

Combination therapy with ezetimibe and statins is recommended in cases of statin intolerance or insufficiency. The objective of this study was to compare the efficacy and safety of combination therapy with ezetimibe and rosuvastatin versus those of rosuvastatin monotherapy in patients with hypercholesterolemia.

The Developmental Nature and Effective Treatment of Stuttering in Children and Adolescents

Stuttering is a potentially debilitating disorder that begins as soon as children begin to talk. For at least 20% of those stuttering in their early years, it becomes a chronic problem into old age. This paper describes the nature of stuttering as it develops through childhood into adulthood. There have been multiple causal theories of stuttering proposed, and these can be divided into those that assume either a psychogenic or a physical etiology. Based on contemporary information, a multifactorial theory of stuttering is presented in which a physical disorder is assumed to cause stuttering, which is in itself influenced by multiple factors. Treatments that attempt to address an assumed psychogenic deficit have not been shown to substantially reduce stuttering. However, state-of-the-art treatments that attempt to address a physical deficit are presented, which conclusively show that stuttering can be substantially reduced for the majority. From the available evidence, stuttering should be now regarded as a physical developmental disorder that can be treated very effectively in children.     

丙戊酸静脉制剂治疗儿童癫痫持续状态的疗效及安全性

目的探讨丙戊酸静脉制剂治疗儿童癫痫持续状态的疗效和安全性.方法对25例采用传统一线药物安定及苯巴比妥治疗无效的惊厥性癫痫持续状态住院患儿,改用丙戊酸静脉制剂以15 mg/kg负荷量,1～2 mg/kg维持量治疗,观察疗效及不良反应.结果丙戊酸静脉制剂治疗儿童癫痫持续状态总有效率92%,有7例患儿出现嗜睡,未见其他不良反应.结论丙戊酸静脉制剂治疗传统一线药物无效的儿童癫痫持续状态安全、有效.     

Familial Atrioventricular Heart Block of Adult Onset: Electrocardiogram and HLA Typing Analysis

EBISAWA, K., et.al .: Familial Atrioventricular Heart Block of Adult Onset: Electrocardiogram and HLA Typing Analysis . A family was investigated because of heart block and sinus arrhythmia. The electrical characteristics were: (1) adult onset in all members; (2) complete heart block with atrial fibrillation in 2, and first- or second-degree heart block in 7 members; and (3) sinus arrhythmia in 3 members. Human leukocyte antigen (HLA) typing was performed. HLA A2, B39, Cw7, and DR12 were positive in 4 of 5 members in the heart block group. In the sinus arrhythmia group, HLA DR12 was positive in all members. In the normal group, none of these HLA typings was positive except one. These findings indicate a tighter relationship between heart block and the HLA locus than previously thought.     

诱导化疗后骨髓缓解程度对儿童核心结合因子相关性急性髓系白血病预后的影响

目的:探讨诱导化疗后骨髓形态学缓解程度对儿童核心结合因子相关性急性髓系白血病(CBF-AML)预后的影响.方法:回顾性分析2008年9月至2018年12月我科收治的157例CBF-AML患儿诱导后反应结果及生存资料.对不同骨髓缓解程度患儿的生存进行对比分析.结果:157例患者中,113例(72.4％)第一个疗程诱导化疗...     

加强型气管插管气囊压迫填塞止血治疗鼻腔后部出血

目的探讨加强型气管插管气囊压迫填塞止血治疗成人鼻腔后部出血的效果。方法选择我院急诊成人鼻腔后部出血78例,随机均分为观察组和对照组。观察组采用小儿加强型气管插管插入患侧鼻腔达后鼻孔,前端气囊充气压迫止血;对照组采用常规后鼻孔填塞法止血。比较两组填塞后72 h止血效果,撤除填塞物后鼻腔再出血发生率、患者疼痛程度、填塞操作时间及并发症发生情况。结果两组填塞后72 h止血效果及并发症发生率比较差异均无统计学意义(P0.05);观察组撤除填塞物鼻腔再出血发生率低于对照组,患者疼痛程度轻于对照组,填塞操作时间短于对照组,差异均有统计学意义(P0.05)。结论应用加强型气管插管气囊压迫填塞止血治疗成人鼻腔后部出血具有简单方便、经济有效、患者痛苦小、并发症少等特点,尤其适用于基层医院。