Primary Prevention of Sudden Cardiac Death: Can We Afford the Cost of Cardioverter-Defibrillators? Data from the Search-MI Registry-Italian Sub-study

Background: Large randomized trials show that in appropriately selected patients with left ventricular dysfunction, implantable cardioverter-defibrillators (ICDs) can improve overall survival at 2–5 years. Since direct implementation of the criteria used in the MADIT II and SCD-HeFT will lead to a marked rise in ICD implants, there is a growing fear that increased use of ICDs may cause a dramatic burden to health care systems. The ICD has traditionally been seen as an expensive form of treatment, which is difficult to accept at the first look. This is mainly due to the nonlinear character of the ICD investment, characterized by high initial expenditure, followed by a deferred pay-off in terms of clinical benefits. Cost-effectiveness analysis may help provide a different perspective on the problem of ICD cost, as may estimation of the daily cost of ICD treatment, assuming a time horizon of 5–7 years—a particularly interesting subject for further registry studies.
Methods and Results: Based on real expenditure data from 2002 to 2005, as recorded in the Search-MI Registry-Italian Sub-study of patients implanted on MADIT II indications, we estimated the daily costs associated with the device and leads. Over a 5–7 year time horizon, the average daily cost was estimated to be €4.60–€6.70. Translation of these figures into U.S. market conditions suggests a daily cost of around $7.90–$11.40.
Conclusions: These findings appear useful to help evaluate the affordability of ICD in comparison with other therapeutic options in a context of limited available economic resources.     

Responses of CDKs and p53 in Delayed Ischemic Neuronal Death

Stroke is a debilitating disease that affects millions each year.While in many cases cerebral ischemic in jury can be limited by effectivw resuscitation or thrombolytic treatment,the injured neurons wither in a process known as delayed neuronal death(DND).Mounting evidence indicates that DND is not simply necrosis played out in slow motion but apoptosis is triggered.Of particular interest are two groups of signal proteins that participate in apoptosis-cyclin dependent kinases(CDKs) and p53-among a myriad of signaling events after an ischemic insult.Recent investigations have shown that CDKs,a family of enzymes initially known for their role in cell cycle regulation,are activated in injured neurons in DND.As for p53,new reports suggest that its up-regulation may represent a failed attempt to rescue in jured neurons,although its up-regulation was previously considered an indication of apoptosis.These observations thus rekindle an old quest to identify new neuroprotective targets to minimize the stroke damage.In this review,the author will examine the evidence that indicates the participation of CDKs and p53 in DND and then introduce pre-clinical data to explore CDK inhibition as a potential neuroprotective target.Finally,using CDK inhibition as an example,this paper will discuss the pertinent criteria for a viable neuroprotective strategy for ischemic in jury.     

Auditory brainstem responses after out-of-hospital cardiac arrest: Are they useful for outcome prediction?

We evaluated whether we could predict the neurologic outcome in 55 out-of-hospital cardiac arrest patients using auditory brainstem responses (ABR). ABR patterns were classified into one of 3 types by evaluation of 5 components: type 1, with all 5 components; type 2, lack of at least one response between the 2nd and 5th components; type 3, with only the first component or no response. The relation between the ABR patterns on the 3rd day following resuscitation and the neurologic outcome on hospital discharge was evaluated. The specificity that the 5 awake patients had type-1 ABR was 38%. The sensitivity that the 10 brain dead patients had type-3 ABR was 60%. In the type-1 ABR patients, the negative predictive value that the patients were awake was 100%. In the type-3 ABR patients, the negative predictive value that the patients became brain dead was 90.9%. These results suggest that ABR on the 3rd post-resuscitation day may not be useful for predicting if patients are awake or become brain dead, although the loss of components may be a sign of morbidity, and the presence of the 2nd or later components indicates possible future prevention of brain death.     

Monolateral hypoplasia of the motor vagal nuclei in a case of sudden infant death syndrome

During the development of motor vagal nuclei (MVN), the neuroblasts of the myeloencephalic basal plate migrate in the dorsolateral direction to form the dorsal motor vagal nucleus (DMVN) and ventrolaterally to form the ventral motor vagal nucleus (VMVN). Those neuroblasts that remain close to the median sulcus will form the hypoglossal nucleus. In support of the congenital origin of the alteration of the MVN in sudden infant death syndrome (SIDS), we report the case of an 8‐month‐old female child who was found dead in her cot. The neuropathological assessment revealed that the medullary triangle of the 4th ventricle floor was asymmetric, owing to the presence of three prominences to the left side of the median sulcus. The medial prominence corresponded to the hypoglossal nucleus, which showed a marked increase in the number of large neurons; the intermediate prominence corresponded to the DMVN whose large neurons were reduced and were recognizable mainly at the level of the medial fringe; the lateral prominence corresponded to the solitary nucleus. The left solitary tract showed a reduction of the transverse diameter. Also, the left VMVN showed marked reduction in the number of neurons. Inflammatory and astrocytic reactions were absent. We suggest that in SIDS cases the hypocellularity of the MVN and the increased number of neurons of the hypoglossal nucleus are intimately related, indicating a congenital alteration due to incomplete migration of the vagal neuroblasts with abnormality of the autonomic cardio‐respiratory control.     

早年父亲去世的心理创伤研究——1例男大学生的深入访谈分析

目的 探讨男孩8岁时父亲去世对其带来的创伤影响。方法 运用质的研究方法，对一名在8岁时经历父亲去世的男大学生进行深入访谈，采用主要概念或主题突出分类的方法进行编码分析。结果 父亲去世使个体产生了强烈的不安全感，严重的自卑感和神经症性的防御机制。结论 父亲去世后，家庭氛围是影响孩子心理健康的重要因素。     

围产儿死亡545例原因分析

目的 探讨围产儿死亡原因，以提高围产期保健工作质量及降低围产儿死亡率。方法 对我院12年来围产儿死亡病历进行回顾性分析。结果 12年间围产儿死亡95例，占16．88‰，死胎64．84％，死产26．37％，新生儿死亡8．79％。围产儿死亡原因依次为早产、胎儿畸形、缺氧综合征、脐带因素、胎位异常、胎盘因素及妊娠并发症。新生儿死亡主要因早产、呼吸窘迫综合症(RDS)所致。结论 加强围产期监护，预防为主，提高产科质量，达到降低围产儿死亡率。     

Analysis of the circumstances at the end of life in children with cancer: Symptoms, suffering and acceptance

BACKGROUND: In an effort to improve the quality of life of children with cancer, this study analyzes the signs and symptoms at the end of life in such children. It is hoped that these data will contribute to the development of appropriate programs to address the challenges faced by these children. PROCEDURE: Between 1994 and 2000, 28 children died after treatment for cancer at Hamamatsu University Hospital, Japan. The circumstances, signs and symptoms at the end of life of these children were analyzed through their medical records. RESULTS: Of the 28 children, the underlying diseases were leukemia/lymphoma (LL group; n=11), brain tumors (BT group; n=7), and other solid tumors (OST group; n=10). Records showed poor appetite (100%), dyspnea (82.1%), pain (75.0%), fatigue (71.4%), nausea/vomiting (57.1%), constipation (46.4%) and diarrhea (21.4%) among these children. Anxiety was reported in 53.6% of the entire group of 28 children; however, no child in the BT group manifested anxiety. However, disturbance of consciousness was reported in all children in the BT group, which was significantly greater than in the other groups. Awareness, fear or acceptance of the imminence of his/her own death as indicated by verbal expression was reported in nine children (32.1%). CONCLUSIONS: Using the data obtained in the present study, we describe situations faced in the terminal care of children. It is important to address the problems revealed by this analysis in order to achieve improvements in both the physical and psychological care of children with terminal cancer.     

外源性p53对不同LET辐射诱导人黑色素瘤细胞系A375死亡途径的影响

目的 观察外源性P53蛋白对不同传能线密度(LET)射线辐照诱导肿瘤细胞凋亡和坏死的影响,并探讨其可能的机制。方法 人黑色素瘤细胞系A375(wild-type p53)经携带人野生型p53基因的腺病毒载体(AdCMV-p53)感染后分别给予X射线和碳离子束照射,采用克隆形成法测定细胞辐射敏感性,Hoechst 33258和吖啶橙-溴化乙锭双染荧光显微镜下观察细胞凋亡和坏死。结果1高LET辐照时,A375细胞和转导人野生型p53基因的A375细胞(A375/p53)的辐射敏感性没有明显差异;2虽然辐射诱导细胞凋亡比例的增加依赖于LET升高,但是无论高LET或低LET,外源性P53蛋白均可有效诱导细胞凋亡。3高LET辐照时,A375细胞的坏死细胞明显高于A375/p53细胞。结论 尽管高LET辐射对A375和A375/p53细胞的存活无明显影响,但是对细胞凋亡的诱导却部分依赖于P53蛋白的功能,P53蛋白可能在调节细胞死亡类型中发挥重要作用。这对临床应用高LET辐射联合p53基因治疗恶性黑色素瘤有一定参考意义。     

End-of-life Models and Emergency Department Care

Many people die in emergency departments (EDs) across the United States from sudden illnesses or injuries, an exacerbation of a chronic disease, or a terminal illness. Frequently, patients and families come to the ED seeking lifesaving or life-prolonging treatment. In addition, the ED is a place of transition-patients usually are transferred to an inpatient unit, transferred to another hospital, or discharged home. Rarely are patients supposed to remain in the ED. Currently, there is an increasing amount of literature related to end-of-life care. However, these end-of-life care models are based on chronic disease trajectories and have difficulty accommodating sudden-death trajectories common in the ED. There is very little information about end-of-life care in the ED. This article explores ED culture and characteristics, and examines the applicability of current end-of-life care models.     

Mutant ryanodine receptors in catecholaminergic polymorphic ventricular tachycardia generate delayed afterdepolarizations due to increased propensity to Ca2+ waves.

AIMS: Mutations in cardiac ryanodine receptors (RyR2s) are linked to catecholaminergic polymorphic ventricular tachycardia (CPVT), characterized by risk of polymorphic ventricular tachyarrhythmias and sudden death during exercise. Arrhythmias are caused by gain-of-function defects in RyR2, but cellular arrhythmogenesis remains elusive. METHODS AND RESULTS: We recorded endocardial monophasic action potentials (MAPs) at right ventricular septum in 15 CPVT patients with a RyR2 mutation (P2,328S, Q4,201R, and V4,653F) and in 12 control subjects both at baseline and during epinephrine infusion (0.05 microg/kg/min). At baseline 3 and during epinephrine infusion, four CPVT patients, but none of the control subjects, showed delayed afterdepolarizations (DADs) occasionally coinciding with ventricular premature complexes. In order to study the underlying mechanisms, we expressed two types of mutant RyR2 (P2,328S and V4,653F) causing CPVT as well as wild-type RyR2 in HEK 293 cells. Confocal microscopy of Fluo-3 loaded cells transfected with any of the three RyR2s showed no spontaneous subcellular Ca(2+) release events at baseline. Membrane permeable cAMP analogue (Dioctanoyl-cAMP) triggered subcellular Ca(2+) release events as Ca(2+) sparks and waves. Cells expressing mutant RyR2s showed spontaneous Ca(2+) release events at lower concentrations of cAMP than cells transfected with wild-type RyR2. CONCLUSION: CPVT patients show DADs coinciding with premature action potentials in MAP recordings. Expression studies suggest that DADs are caused by increased propensity of abnormal RyR2s to generate spontaneous Ca(2+) waves in response to cAMP stimulation. Increased sensitivity of mutant RyR2s to cAMP may explain the occurrence of arrhythmias during exercise or emotional stress in CPVT.