层粘连蛋白受体Ⅰ与hPeriod1相互作用的研究

目的寻找与节律蛋白hPeriod1（hPer1）相互作用的蛋白，并对筛选出的层粘连蛋白受体Ⅰ（Lamr1）在节律系统中的功能作初步研究。方法分别构建pGAD rec／脑cDNA文库和pGBKT7／hPer1bHLH—PAS重组诱饵蛋白质粒，酵母双杂交筛选下丘脑里与hPer1相互作用的蛋白。利用RT—PCR技术检测新蛋白在脑、肺、心、肝、肾组织中的表达及在SH—SY5Y细胞中的节律性质。通过RNA干扰技术研究新蛋白与hPer1的关系。结果通过酵母双杂交筛选，证明Lamr1能与hPer1蛋白发生相互作用。该蛋白在脑、肺、心、肝、肾组织广泛表达，灰度比较显示经马血清诱导后的SH～SY5Y细胞的hPer1表达呈现近日节律，而Lamr1表达无节律变化。RNA干扰显示hPer1表达下调不影响Lamr1的表达。结论Lamr1能与hPer1蛋白发生相互作用，但其表达在RNA水平无节律变化。Lamr1参与细胞的黏附、转移和侵袭。其前体蛋白作为核蛋白参与细胞蛋白的合成。Lamr1可能参与hPer1相关的生物节律系统的信号传出。     

PMA诱导C6细胞rPer1,rDbp基因的近日节律表达

目的寻找一种新的体外节律诱导剂以研究C6神经胶质瘤细胞近日节律基因的表达情况。方法采用PMA（phorbol 12-myristate 13-acetate），100nmol／L）及50％的马血清刺激体外培养的小鼠NIH-3T3细胞。RT-PCR检测不同时间点mPer1 mRNA的表达水平，比较两者的诱导效率；PMA刺激体外培养的大鼠C6神经胶质瘤细胞，RT—PCR检测不同时间点rPer1，rDbp mRNA的表达水平。结果PMA及50％的马血清均能诱导NIH-3T3细胞mPer1的近日节律表达且诱导效率近似；并首次发现C6细胞的rPer1，rDbp基因存在着近日节律振荡。结论PMA是一种有效的体外节律诱导剂；经PMA诱导后，C6细胞的节律基因存在近日振荡，为体外研究授时因子对近日节律的导引机制提供依据。     

小鼠外周血白细胞节律基因bmal1、clock、cry1、per1表达的近日节律性研究

目的 探讨12 h光照、12h黑暗交替（12 h-light and 12 h-dark cycle,12L/12D）光制条件下,小鼠外周血白细胞中4种节律基因bmal1、clock、cry1、per1近日节律性的表达特点. 方法 将48只雄性C57/BL6小鼠在12L/12D光制条件下饲养4周后,按随机数字表法分为6组,每组8只.分别在6个时相点（9：00、13：00、17：00、21：00、1：00、5：00）取外周血并分离白细胞.抽提总RNA,利用实时聚合酶链反应（polymerase chain reaction,PCR）方法检测小鼠外周血白细胞中bmal1、clock、cry1、per1 4种节律基因的mRNA水平.用余弦函数作曲线拟合,获取节律参数.并经one-ANOVA分析比较基因表达峰值和谷值的差异. 结果 在明暗交替光制条件下,bmal1、clock、cry1、per1 4种基因存在明显的近日节律性,各基因表达的峰值明显高于谷值（P＜0.01）.利用拟合方程预测的clock表达峰值相位时间在5：00左右,雨bmal1、cry1、per1基因表达的峰值时间在13：00-15：00左右.clock表达的峰值时间比bmal1超前,峰值及振幅也比bmal1高（P＜0.01）;而cry1和per1表达的峰值时间、峰值大小比较接近. 结论 C57/BL6小鼠外周血白细胞bmal1、clock、cry1、per1基因表达存在明显的近日节律性.clock在正反馈中的作用强于bmal1,而cry1、per1在负反馈中的作用相似.     

Methylation analysis of circadian clock gene promoters in forensic autopsy specimens

DNA methylation in gene promoter regions influences gene expression. Circadian clock genes play an important role in the formation of a biological clock and aberrant methylation of these genes contributes to several disorders. In this study, we examined forensic autopsy specimens to determine whether DNA methylation status in the promoter regions of nine circadian clock genes (Per1, Per2, Per3, Cry1, Cry2, Bmal1, Clock, Tim, and Ck1e) is related to a change in acquired diathesis and/or causes of death. Methylation-specific PCR and direct sequencing methods revealed that the promoters of Per1, Cry2, Bmal1, Clock, and Ck1e were unmethylated in all the forensic autopsy specimens, while the promoters of Per2, Per3, Cry1, and Tim were partially methylated. Methylation status varied between individuals and between tissues in the same patient. A detailed analysis of methylation patterns in the Cry1 promoter region revealed that the patterns also varied between individuals and the Cry1 promoter had highly methylated patterns in two cases that had been exposed to methamphetamine. These results suggest that the methylation status of clock gene promoters varies between individuals. Methamphetamine use may influence methylation in the Cry1 gene promoter region and disturb circadian rhythmicity.     

hPeriod1PAS结构域相互作用蛋白的筛选和研究

目的寻找与近日节律系统核心基因Period1（Per1）相互作用的新蛋白,揭示近日节律相关的可能信号通路。方法采用酵母双杂交方法,以人Per1的PAS结构域为诱饵,扫描人下丘脑cDNA文库,并通过体外转录、免疫共沉淀验证蛋白间相互作用;通过RT—PCR检测RACK1（receptors for activated Ckinase）表达的组织特异性及节律性;运用RNAi技术初步研究RACK1与Per1的信号联系。结果人下丘脑区域RACK1蛋白与Per1存在相互作用;RACK1在多器官组织保守表达,但其表达未呈现明显节律性;上调及下调Per1表达,RACK1的RNA水平无显著变化。结论细胞内接头分子RACK1是一种新的Per1作用蛋白,可能介导、调控Per1的功能。     

Tissue and body fluid distribution of lidocaine and monoethylglycinexylidide in critical care patients who survived for various periods

We investigated the tissue and body fluid distribution of lidocaine and monoethylglycinexylidide (MEGX), an active metabolite of lidocaine, in 20 critical care patients who received lidocaine jelly for intubation, and survived for various periods after treatments. Our study population consisted of seven patients (Group A) who were transported to hospitals in conscious state and survived for 1–56 h, six patients (Group B) who arrived at hospitals in comatose state and survived for 5–91 h, and seven patients (Group C) who were in cardiopulmonary arrest on arrival at hospitals and survived for 3–59 h after their heartbeat was recovered by cardiopulmonary resuscitation. At autopsy, blood from different sources, cerebrospinal fluid, the cerebrum, lung, liver, kidney, and femoral muscle were collected from each cadaver for analysis of lidocaine and MEGX by gas chromatography with flame thermionic detection. This is the first report dealing with detailed distribution of MEGX in human tissues and body fluids for critical care patients. All patients were positive for lidocaine. MEGX was detected in five patients from Group A, all patients from Group B, and four patients from Group C. The liver-to-kidney ratios for lidocaine/MEGX were 0.28–1.76/0.50–0.67, and the cerebrum-to-cerebrospinal fluid ratios for lidocaine/MEGX were 0.54–3.63/1.81–3.13, respectively, for Group A; 0.14–0.55/0.05–0.59 and 1.22–4.00/1.64–3.44, respectively, for Group B; 0.22–0.95/0.68–1.28 and 1.15–6.44/10.2, respectively, for Group C. The concentration ratios of MEGX to lidocaine in blood in Groups A, B, and C were in the ranges of 0.01–1.08, 0.08–0.76, and 0.09–0.38, respectively. Based on our results, we propose that the measurements of MEGX distribution together with that of precursor lidocaine in various tissues and body fluids are useful for accurate assessment of the state of patients who receive medical treatment that is followed by death. The MEGX-to-lidocaine ratio in blood seems to be a useful test for evaluating antemortem liver function.     

The attachments of the anteromedial and posterolateral fibre bundles of the anterior cruciate ligament

The aim of this study was to describe the anatomical locations of the femoral attachments of the anteromedial (AM) and posterolateral (PL) bundles of the anterior cruciate ligament (ACL). Twenty-two human cadaver knees with intact ACLs were used. The femoral attachments of the two bundles were identified, marked and photographed. They were measured and described in terms of the o’clock positions parallel to the femoral long axis and parallel to the roof of the intercondylar notch. The centres of the bundles were also measured in a high–low and a superficial-deep manner referencing from the centre of the posterior femoral condyle, and with respect to their positions within a measurement grid defined in this study. The bulk of the AM bundle was attached between the 9.30 and 11.30 o’clock positions and the PL bundle between the 8.30 and 10 o’clock positions. The AM and PL bundles were consistently found in specific zones of the measurement grid. Using the posterior condyle reference method, the centre of the AM bundle was at 68 ± 7% (range 57–78) in a shallow–deep direction and 55 ± 5% (44–62) in a high–low direction. The PL bundle was found at 56 ± 8% (40–73) in a shallow–deep direction, and 62 ± 7.0% (40–70) in a high–low direction. The attachment was oriented at 37° to the femoral long axis. The results from this study could be used to guide ACL reconstruction techniques.     

Comparison of inversion recovery fast spin-echo (FSE) with T2-weighted fat-saturated FSE and T1-weighted MR imaging in bone marrow lesion detection

 Objective To prospectively compare inversion recovery (IR) fast spin-echo (FSE) with T1-weighted spin-echo (SE) and T2-weighted chemical-shift fat-saturated (FS) FSE magnetic resonance sequences in the detection of bone marrow abnormality. Design. Twenty-nine sets of T1-weighted SE [400–640/10–20 (TR/TE)], T2-weighted FS-FSE [2400–3800/91–112/8 (TR/TE/ETL)], and IR-FSE [3700–6000/12–14/170/8 (TR/TE/T1/ETL)] images were acquired with a 1.5-T magnet in 27 patients with bone marrow lesions. The visibility, margination, and extent of 41 lesions, image quality, contrast, and artifacts were qualitatively and quantitatively compared. Results. The lesions were more conspicuous on the IR-FSE than on the T1-weighted SE and T2-weighed FS-FSE images. The extent of lesions was similar for all three sequences. Image quality was better and there were fewer motion artifacts on the T1-weighted images. The mean lesion contrast-to-noise ratio was significantly higher on the T1-weighted images (p<0.05). Conclusion. The IR-FSE sequence is highly sensitive for detecting bone marrow pathology, with scan time comparable to the T1-weighted SE and T2-weighted FS-FSE sequences.     

Time-dependent appearance of intrathrombus neutrophils and macrophages in a stasis-induced deep vein thrombosis model and its application to thrombus age determination

We immunohistochemically examined neutrophils and macrophages in venous thrombi, which developed in the ligation of the inferior vena cava (IVC). Myeloperoxidase (MPO)-positive neutrophils and F4/80-positive macrophages were detected in the whole course of thrombi after IVC ligation. Morphometrically, the number of neutrophils was greatest at 1 day after IVC ligation and, thereafter, gradually decreased with an increase of the post-ligation interval. In contrast, the number of macrophages peaked at 7 days after ligation. The number of intrathrombus neutrophils was significantly higher than that of intrathrombus macrophages at 1 and 3 days, and the average ratios of neutrophils to macrophages (N/M ratios) were 6.8 ± 1.1 (4.8–9.0) and 2.5 ± 0.4 (1.7–4.2) at 1 and 3 days, respectively. After more than 5 days, all samples had N/M ratios of <2.0 (0.2–1.4). These observations suggest that an N/M ratio of >2.0 indicates a thrombus age of 1–3 days. To differentiate between 1- and 3-day-old thrombi, an N/M ratio markedly exceeding 5.0 strongly indicates an age of 1 day. Furthermore, an N/M ratio of 1.0 or less probably indicates an age of more than 5 days. The present study demonstrated that the immunohistochemical detection of intrathrombus neutrophils and macrophages was suitable to determine the age of venous thrombi.     

miRNA analysis in vitreous humor to determine the time of death: a proof-of-concept pilot study

We hypothesized that miRNAs present in vitreous humor could be a sort of “biological black box,” storing information about physiological and environmental circumstances at death. As a proof of concept, we analyzed the vitreous humor miRNA signature to explore its forensic potential applications, such as determining the time of the day at death. The miRNAs present in vitreous humor from individuals who died at daytime or at nighttime were analyzed by quantitative real-time polymerase chain reaction (qPCR) array. Target miRNAs showing significant differences between groups were studied in a larger sample by individual qPCR assays. After array analysis of miRNAs in seven samples, significant expression differences were detected between individuals who died at daytime and at nighttime regarding mir-34c, mir-541, mir-888, mir-484, and mir-142-5p. miR-222 appeared as the best reference gene. The results were replicated in 34 vitreous humor samples, and the day–night differences were confirmed for miR-142-5p and miR-541, suggesting that miRNA levels may be related to either the ambient light or the circadian clock at the time of death. There was no correlation between miRNA levels and the time elapsed after death, suggesting that they were stable at least for 24 h. In conclusion, this report supports the potential forensic utility of the analysis of miRNAs in the vitreous humor in applications such as determining the time of death.     

Application of a classification system focusing on potential asphyxia for cases of sudden unexpected infant death

Current classification schemes for sudden unexpected infant death (SUID) may not be optimal for capturing scene events that potentially predispose to asphyxia. (1) To compare causes of death in a group of SUID cases assigned by multiple reviewers using our recently published classification scheme for SUID that is based on asphyxial risk at the death scene, and (2) To compare these newly assigned causes of death to that originally assigned by the medical examiners of record who performed the autopsies. Five reviewers independently assigned causes of death for 117 cases of SUID, including 83 originally diagnosed as sudden infant death syndrome (SIDS), accessioned into the San Diego SIDS/SUDC Research Project from the San Diego County Medical Examiner’s Office. The diagnostic categories are: A: SIDS; B: Unexplained—Potentially Asphyxia; C: Unexplained—Other Potential Causes of Death; D: Unclassified—Other; E: Unclassified; and F: Known Cause of Death. The reviewers collectively opined that conditions at the death scene contributed to or caused death in 32–50% of all of the 117 cases as well as in 40–59% of the 83 originally diagnosed SIDS cases. Another cause of death was considered plausible in 2–12% of the SIDS cases. Application of this new classification system resulted in 55–69% decrease in SIDS diagnoses. Asphyxia as a potential contributor to, or as the specific cause of death, appears to exist in a large percentage of cases designated as SIDS using other classification schemes. When certifiers use a classification system that focuses upon potential asphyxia in determining the cause of death the incidence of SIDS dramatically declines.     

Rapid analysis of sertraline,fluvoxamine, and paroxetine in serum specimens by LC-MS-MS using a new polymer column

Three selective serotonin reuptake inhibitors (sertraline, fluvoxamine, and paroxetine) in human serum specimens were analyzed by liquid chromatography-tandem mass spectrometry using a new polymer column (Shim-pack MAYI-ODS), which enabled direct injection of crude biological samples without complicated pretreatments. Quantitation was made by mass chromatography for each product ion using dextromethorphan as internal standard. The recoveries of the three drugs from human serum were 29.2%–45.7% at 20 ng/ml and 52.0%–53.7% at 80 ng/ml. The regression equations showed good linearity for the three drugs in the range of 5–80 ng/ml. Each drug had a detection limit of 1–3 ng/ml. Thus, the present method of using a new polymer column is effective for rapid and sensitive analysis of both therapeutic and toxic levels of sertraline, fluvoxamine, and paroxetine in biological specimens.     

Fatal overdose with a combination of SNRIs venlafaxine and duloxetine

Drugs for the treatment of depressive disorders, including SNRIs (serotonin noradrenaline reuptake inhibitors) venlafaxine and duloxetine, are widely prescribed as they have a high therapeutic to toxicity ratio. In rare cases, adverse effects may be severe, usually due to iatrogenic, accidental or intentional self-overdose that cause the excessive accumulation of serotonin and noradrenaline in synaptic clefts. Lethal intoxication with a combination of venlafaxine and duloxetine (postmortem blood concentrations 24 mg/L and 0.97 mg/L, respectively) without co-ingested substances, comorbidities or injuries that could have an unknown contribution to a fatal outcome is presented for the first time in the following case report, with a comprehensive clinical history, and complete results of the performed analyses. The cause of death was a serotonin syndrome that progressed to death in approximately six hours and 15 min after the suicidal ingestion of venlafaxine and duloxetine. Despite the high therapeutic to toxicity ratio SNRIs, which are reserved for patients with severe forms of depressive disorders and a higher suicidal tendency, they should be cautiously prescribed and handed over in smaller packages to make them easier to follow, and thus avoid accumulation within the patient’s reach.     

Prognostic value of sympathetic innervation and cardiac asynchrony in dilated cardiomyopathy

Purpose  The purpose of the study is to examine prognostic values of cardiac I-123 metaiodobenzylguanidine (MIBG) uptake and cardiac dyssynchrony in patients with dilated cardiomyopathy (DCM). Materials and methods  Ninety-four patients with non-ischemic DCM underwent I-123 MIBG imaging for assessing cardiac sympathetic innervation and equilibrium radionuclide angiography. Mean phase angles and SD of the phase histogram were computed for both right ventricular (RV) and left ventricular (LV). Phase measures of interventricular (RV–LV) and intraventricular (SD–RV and SD–LV) asynchrony were computed. Results  Most patients were receiving beta-blockers (89%) and angiotensin-converting enzyme inhibitors (88%). One patient (1%) was lost to follow-up, six had cardiac death (6.4%), eight had heart transplantation (8.6%), and seven had unplanned hospitalization for heart failure (7.5%; mean follow-up: 37 ± 16 months). Patients with poor clinical outcome were older, had higher The New York Heart Association functional class, impaired right ventricular ejection fraction and left ventricular ejection fraction, and impaired cardiac I-123 MIBG uptake. On multivariate analysis, I-123 MIBG heart-to-mediastinum (H/M) uptake ratio <1.6 was the only predictor of both primary (cardiac death or heart transplantation, RR = 7.02, p < 0.01) and secondary (cardiac death, heart transplantation, or recurrent heart failure, RR = 8.10, p = 0.0008) end points. Conclusions  In patients receiving modern medical therapy involving beta-blockers, I-123 MIBG uptake, but not intra-LV asynchrony, was predictive of clinical outcome. The impact of beta-blockers on the prognostic value of ventricular asynchrony remains to be clarified.     

Ethyl glucuronide and ethyl sulfate in autopsy samples 27 years after death

The unique case of a 50-year-old known alcoholic whose corpse was exhumed 27 years after death is reported. The man apparently committed suicide by hanging, but many years later the case was questioned and homicide—linked to a long-lasting serial killer case—was suspected. Thus, the corpse was exhumed, and at the autopsy it was found to be naturally mummified. This fact permitted the analysis of body tissues with the aim to investigate the persistence of ethanol conjugates in the biological material 27 years after death. Fragments of liver and kidney, a blood clot, and a hair strand were collected and submitted to liquid chromatography tandem mass spectrometry analysis. Ethyl glucuronide (EtG) and ethyl sulfate (EtS) were identified and quantified in the liver, the kidney, and the blood clot. Hair analysis was found to be severely affected by ion suppression even after solid phase extraction. Consequently, EtG was identified in all hair segments (0–3 cm, 3–6 cm, and 6–10 cm), but no reliable quantification could be carried out. In summary, our findings demonstrate that, notwithstanding the expected conjugate degradation, EtG and EtS can be indicative of ante-mortem use of alcohol even many years after death.     

Baseline metabolic tumor burden on FDG PET/CT scans predicts outcome in advanced NSCLC patients treated with immune checkpoint inhibitors

We aimed to evaluate if imaging biomarkers on FDG PET are associated with clinical outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). In this retrospective monocentric study, we included 109 patients with advanced NSCLC who underwent baseline FDG PET/CT before ICI initiation between July 2013 and September 2018. Clinical, biological (including dNLR = neutrophils/[leukocytes minus neutrophils]), pathological and PET parameters (tumor SUVmax, total metabolic tumor volume [TMTV]) were evaluated. A multivariate prediction model was developed using Cox models for progression-free survival (PFS) and overall survival (OS). The association between biomarkers on FDG PET/CT and disease clinical benefit (DCB) was tested using logistic regression. Eighty patients were eligible. Median follow-up was 11.6 months (95%CI 7.7–15.5). Sixty-four and 52 patients experienced progression and death, respectively. DCB was 40%. In multivariate analyses, TMTV > 75 cm3 and dNLR > 3 were associated with shorter OS (HR 2.5, 95%CI 1.3–4.7 and HR 3.3, 95%CI 1.6–6.4) and absence of DCB (OR 0.3, 95%CI 0.1–0.9 and OR 0.4, 95%CI 0.2–0.9). Unlike TMTV, dNLR was a significant prognostic factor for PFS (HR 1.9, 95%CI 1.1–3.3) along with anemia (HR 1.9, 95%CI 1.2–3.8). No association was observed between tumor SUVmax and PFS or OS. Baseline tumor burden (TMTV) on FDG PET/CT scans and inflammatory status (dNLR) were associated with poor OS and absence of DCB for ICI treatment in advanced NSCLC patients, unlike tumor SUVmax, and may be used together to improve the selection of appropriate candidates.     

“Ecstasy” associated deaths: what is a fatal concentration ? Analysis of a case series

Amphetamine derivative drugs, particularly 3,4-methylenedioxymethamphetamine (MDMA), commonly known as ecstasy, are popular recreational drugs. MDMA is associated with causing death by a number of mechanisms, including hyperpyrexia, cardiac arrhythmia water intoxication and liver failure. Seventy-seven deaths where MDMA was detected in body fluids/organs were reviewed. Of these cases 59 deaths had MDMA present in blood. In 13 cases death was attributable to the toxic effects of MDMA alone with a range of 0.478–53.9 mg/l, mean 8.43 mg/l, median 3.49 mg/l. In 22 cases death was due to polydrug use, with an MDMA range of 0.04–41.5 mg/l, mean 2.90 mg/l, median 0.76 mg/l. In 24 cases death was due to trauma with an MDMA range of 0.035–4.81 mg/l, mean 0.862 mg/l, median 0. 483 mg/l. There is considerable overlap between the concentration of MDMA seen in deaths from direct MDMA toxicity and deaths associated with trauma. These findings show, that like other stimulant drugs, no specific concentration can be used to determine death without consideration of the history and full autopsy findings.     

Evaluation of mRNA markers for estimating blood deposition time: Towards alibi testing from human forensic stains with rhythmic biomarkers

Determining the time a biological trace was left at a scene of crime reflects a crucial aspect of forensic investigations as – if possible – it would permit testing the sample donor’s alibi directly from the trace evidence, helping to link (or not) the DNA-identified sample donor with the crime event. However, reliable and robust methodology is lacking thus far. In this study, we assessed the suitability of mRNA for the purpose of estimating blood deposition time, and its added value relative to melatonin and cortisol, two circadian hormones we previously introduced for this purpose. By analysing 21 candidate mRNA markers in blood samples from 12 individuals collected around the clock at 2 h intervals for 36 h under real-life, controlled conditions, we identified 11 mRNAs with statistically significant expression rhythms. We then used these 11 significantly rhythmic mRNA markers, with and without melatonin and cortisol also analysed in these samples, to establish statistical models for predicting day/night time categories. We found that although in general mRNA-based estimation of time categories was less accurate than hormone-based estimation, the use of three mRNA markers HSPA1B, MKNK2 and PER3 together with melatonin and cortisol generally enhanced the time prediction accuracy relative to the use of the two hormones alone. Our data best support a model that by using these five molecular biomarkers estimates three time categories, i.e. night/early morning, morning/noon, and afternoon/evening with prediction accuracies expressed as AUC values of 0.88, 0.88, and 0.95, respectively. For the first time, we demonstrate the value of mRNA for blood deposition timing and introduce a statistical model for estimating day/night time categories based on molecular biomarkers, which shall be further validated with additional samples in the future. Moreover, our work provides new leads for molecular approaches on time of death estimation using the significantly rhythmic mRNA markers established here.     

Prognostic value of stress 99mTc-tetrofosmin myocardial perfusion imaging in predicting all-cause mortality: a 6-year follow-up study

Purpose The aim of this study was to ascertain whether stress myocardial perfusion imaging can independently predict long-term mortality.Methods We studied 1,386 patients with known or suspected coronary artery disease by means of stress ^99mTc-tetrofosmin myocardial perfusion tomography. The end point during follow-up was death from any cause. Mortality rates were compared with that in a reference population using calculated age- and gender-specific data in the general population.Results Mean age was 60±11 years. There were 608 (44%) women. Perfusion abnormalities were fixed in 416 (30%) patients and reversible in 445 (32%) patients. During a mean follow-up of 6±1.9 years, 290 (21%) patients died. The annual mortality was 1.7% in patients with normal perfusion and 5.2% in patients with abnormal perfusion. Patients with multivessel distribution of perfusion abnormalities had the highest annual mortality (6.2%). The annual mortality in the reference population was 3.2%. In a multivariate analysis model, predictors of death were age [risk ratio (RR)=1.06, 95% CI 1.04–1.07], male gender (RR=2, CI 1.6–2.6), history of heart failure (RR=2.3, CI 1.8–3.1), diabetes mellitus (RR=2.1, CI 1.6–2.7), smoking (RR=1.8, CI 1.4–2.3), reversible perfusion defects (RR=1.8, CI 1.4–2.5) and fixed perfusion defects (RR=1.7, CI 1.3–2.1).Conclusion Myocardial perfusion abnormalities on stress ^99mTc-tetrofosmin tomography are independently associated with long-term risk of death. The extent of perfusion abnormalities is a major determinant of mortality. The presence of normal perfusion is associated with a lower mortality compared with the general population.     

Hyperthermia deaths among children in parked vehicles: an analysis of 231 fatalities in the United States, 1999–2007

Motor vehicle-related child hyperthermia fatalities (MVRCHF) have risen slightly in the past decade, but little research has been done investigating the circumstances surrounding MVRCHF. In order to address gaps in our understanding, the current study describes MVRCHF circumstances among children <1–14 years of age in the United States from 1999 to 2007. Three sources were used to identify child hyperthermia death cases in the United States from 1999 to 2007: the Centers for Disease Control and Prevention’s Compressed Mortality File (1999–2004), the Golden Gate Weather Service’s public MVRCHF database (2003-Present), and an independent internet search. Data about the victim’s characteristics and the circumstances surrounding the death were extracted. From 1999 to 2007, 231 MVRCHF were identified. Children were left unattended in >80% of cases, 25% of victims were playing at the time of death, and 60% were male. On average, the core body temperature was 107.2°F after being left inside the vehicle for an average of 4.6 h. The largest number of deaths occurred in the South, followed by the West, Midwest, and Northeast. Parents were found to be accountable for 2/3 of the hyperthermia deaths. The geographic distribution of incidence may be attributable to two major influences: (1) regional climate differences; and (2) population characteristics. The accountability of parents for MVRCHF is likely due to the exposure-risk concept, in which the situation/circumstances increase the injury probability.