Stroke events, and case fatalities in Switzerland based on hospital statistics and cause of death statistics

OBJECTIVE: In Switzerland there is a shortage of population-based information on stroke incidence and case fatalities (CF). The aim of this study was to estimate stroke event rates and both in- and out-of-hospital CF rates. METHODS: Data on stroke diagnoses, coded according to I60-I64 (ICD 10), were taken from the Federal Hospital Discharge Statistics database (HOST) and the Cause of Death database (CoD) for the year 2004. The number of total stroke events and of age- and gender-specific and agestandardised event rates were estimated; overall CF, in-hospital and out-of-hospital, were determined. RESULTS: Among the overall number of 13 996 hospital discharges from stroke (HOST) the number was lower in women (n = 6736) than in men (n = 7260). A total of 3568 deaths (2137 women and 1431 men) due to stroke were recorded in the CoD database. The number of estimated stroke events was 15 733, and higher in women (n = 7933) than in men (n = 7800). Men presented significantly higher age-specific stroke event rates and a higher age-standardised event rate (178.7/100 000 versus 119.7/100 000). Overall CF rates were significantly higher for women (26.9%) than for men (18.4%). The same was true of out-of-hospital CF but not of in-hospital CF rates. CONCLUSION: The data on estimated stroke events obtained indicate that stroke discharge rate underestimates the stroke event rate. Out-of-hospital deaths from stroke accounted for the largest proportion of total stroke deaths. Sex differences in both number of total stroke events and deaths could be explained by the higher proportion of women than men aged 55+ in the Swiss population.

Elevated body core temperature in medico-legal investigation of violent death

Pathologically elevated body core temperature, measured at the death scene, is an important finding in medico-legal investigation of violent deaths. An abnormally high rectal temperature at any death scene may point to an underlying pathology, the influence of certain drugs or a hidden cerebral traumatism, and death by suffocation which would remain undetected without further medico-legal investigations. Furthermore, hyperthermia and fever, if unrecognized, may result in an erroneous forensic estimation of time since death in the early postmortem period by the "Henssge method." By a retrospective study of 744 cases, the authors demonstrate that hyperthermia is a finding with an incidence of 10% of all cases of violent death. The main causes are: influence of drugs, malignant tumors, cerebral hypoxia as a result of suffocation, infections, and systemic inflammatory disorders. As a consequence it must be stated, that hyperthermia must be excluded in every medico-legal death scene investigation by a correct measurement of body core temperature and a comparison between the cooling rate of the body and the behavior of early postmortem changes, notably livor and rigor mortis.

Mammary epithelial-specific knockout of the ephrin-B2 gene leads to precocious epithelial cell death at lactation

The family of Eph receptor tyrosine kinases and their membrane bound ligands, the ephrins, are involved in a wide variety of morphogenic processes during embryonic development and adult tissue homeostasis. Receptor-ligand interaction requires direct cell-cell contact and results in forward and reverse signaling originating from the receptor and ligand, respectively. We have previously shown that EphB4 and ephrinB2 are differentially expressed during the development of the adult mammary parenchyma. Overexpression of EphB4 in the mammary epithelium of transgenic mice leads to perturbations in mammary epithelial morphology, motility and growth. To investigate the role of ephrinB2 signaling in mammary gland biology, we have established transgenic mice exhibiting conditional ephrinB2 knockout in the mammary epithelium. In homozygote double transgenic CreLox mice, specific knockout of ephrinB2 occurred in the mammary epithelium during the first pregnancy-lactating period. Abolishing ephrinB2 function led to severe interference with the architecture and functioning of the mammary gland at lactation. The morphology of the transgenic lactating glands resembled that of involuting controls, with decreased epithelial cell number and collapsed lobulo-alveolar structures. Accordingly, massive epithelial cell death and expression of involution-specific genes were observed. Interestingly, in parallel to cell death, significant cell proliferation was apparent, suggestive of tissue regeneration.

Ventricular arrhythmias and sudden death in adults after a Mustard operation for transposition of the great arteries

AIMS: To examine the prevalence of sustained ventricular tachycardia (VT) and sudden death (SD) in adults with atrial repair of transposition of the great arteries (TGA) and to determine associated risk factors. METHODS AND RESULTS: In a single-centre review, we studied the outcome of 149 adults (mean age 28 +/- 7 years) who had undergone a Mustard operation for TGA. During a mean follow-up of 9 +/- 6 years, sustained VT and/or SD occurred in 9% (13/149) of the cohort. Sustained VT/SD was more likely to occur in patients with associated anatomic lesions [hazard ratio (HR) 4.9, 95% CI 1.5-16.0], with NYHA class >or=III (HR 9.8, 95% CI 3.0-31.6) and with an impaired subaortic right ventricular (RV) ejection fraction (EF) (HR 2.2, 95% CI 1.2-4.0 per 10% decrease in EF). There was an inverse correlation between the RV-EF and both age and QRS duration. Patients with a QRS duration >or=140 ms were at highest risk of sustained VT/SD (HR 13.6, 95% CI 2.9-63.4). Atrial tachyarrhythmia was detected in 66 (44%) patients, but was not a statistically significant predictor of sustained VT/SD in our adult population (HR 2.7, 95% CI 0.6-13.0). CONCLUSION: Sustained VT/SD in adults after a Mustard operation for TGA are more common than previously described. Age, systemic ventricular function, and QRS duration are interrelated and are associated with VT/SD. A QRS duration >or=140 ms helps to identify the high risk patient.

Why Death Matters: Understanding Gameworld Experience

This article presents a study of the staging and implementation of death and the death penalty in a number of popular MMOGs and relates it to players general experience of gameworlds. Game mechanics, writings and stories by designers and players, and the results of an online survey are analysed and discussed. The study shows that the death penalty is implemented much in the same way across worlds; that death can be both trivial and non-trivial, part of the grind of everyday life, or essential in the creation of heroes, depending on context. In whatever function death may serves, it is argued that death plays an important part in the shaping and emergence of the social culture of a world, and in the individual players experience of life within it.

Sellar fracture followed by sudden death: an autopsy case

The authors describe a case of sellar fracture followed by sudden death. The victim was involved in a wrangle. The autopsy revealed facial damage and sellar fracture and no evidence of cerebral damage, except for a mild subarachnoid hemorrhage in the left parietotemporal regions and undersurface of both frontal lobes. Sellar fracture is a rare and severe entity, associated with serious complications, which is frequently diagnosed postmortem. In any case, death is rarely a direct consequence of the sellar fracture itself and is usually considered to be the result of associated cerebral trauma. This case prompted us to screen the literature on sellar fracture to gain a better understanding of the mechanism of death.

Cell death in immune thrombocytopenia: novel insights and perspectives

Immune thrombocytopenia (ITP) is a complex disease. The pathogenic and clinical heterogeneity of ITP is reflected by reports on variability in patient history and treatment response, in concert with recent evidence from mechanistic studies. Programmed cell death (PCD) pathways are thought to play a peculiar role in the megakaryocyte lineage in terms of hemostasis and the generation and function of megakaryocytes and platelets; unbalanced genetic or environmental disturbances of these tightly regulated pathways may cause thrombocytopenia. Dysregulated PCD has also been linked to peripheral platelet destruction, intramedullary apoptosis, and inefficient thrombopoiesis in ITP. In this article, we discuss novel and controversial findings on the role of PCD in the megakaryocyte lineage and their potential implications in terms of pathogenesis, diagnosis, and treatment of ITP.

Nitric oxide induces cell death in canine cruciate ligament cells by activation of tyrosine kinase and reactive oxygen species

BACKGROUND: There is increasing evidence suggesting that development of progressive canine cranial cruciate ligament (CCL) rupture involves a gradual degeneration of the CCL itself, initiated by a combination of factors, ranging from mechanical to biochemical. To date, knowledge is lacking to what extent cruciate disease results from abnormal biomechanics on a normal ligament or contrary how far preliminary alterations of the ligament due to biochemical factors provoke abnormal biomechanics. This study is focused on nitric oxide (NO), one of the potential biochemical factors. The NO-donor sodium nitroprusside (SNP) has been used to study NO-dependent cell death in canine cranial and caudal cruciate ligament cells and to characterize signaling mechanisms during NO-stimulation. RESULTS: Sodium nitroprusside increased apoptotic cell death dose- and time-dependently in cruciate ligamentocytes. Cells from the CCL were more susceptible to apoptosis than CaCL cells. Caspase-3 processing in response to SNP was not detected. Testing major upstream and signal transducing pathways, NO-induced cruciate ligament cell death seemed to be mediated on different levels. Specific inhibition of tyrosine kinase significantly decreased SNP-induced cell death. Mitogen activated protein kinase ERK1 and 2 are activated upon NO and provide anti-apoptotic signals whereas p38 kinase and protein kinase C are not involved. Moreover, data showed that the inhibition reactive oxygen species (ROS) significantly reduced the level of cruciate ligament cell death. CONCLUSIONS: Our data support the hypothesis that canine cruciate ligamentocytes, independently from their origin (CCL or CaCL) follow crucial signaling pathways involved in NO-induced cell death. However, the difference on susceptibility upon NO-mediated apoptosis seems to be dependent on other pathways than on these tested in the present study. In both, CCL and CaCL, the activation of the tyrosine kinase and the generation of ROS reveal important signaling pathways. In perspective, new efforts to prevent the development and progression of cruciate disease may include strategies aimed at reducing ROS.

Risk factors for death and unwanted early slaughter in Swiss veal calves kept at a specific animal welfare standard

Calf losses (CL, mortality and unwanted early slaughter) in veal production are of great economic importance and an indicator of welfare. The objective of the present study was to evaluate CL and the causes of death on farms with a specific animal welfare standard (SAW) which exceeds the Swiss statutory regulations. Risk factors for CL were identified based on information about management, housing, feeding, and medication. In total, 74 production cohorts (2783 calves) of 15 farms were investigated. CL was 3.6%, the main causes of death were digestive disorders (52%), followed by respiratory diseases (28%). Factors significantly associated with an increased risk for CL were a higher number of individual daily doses of antibiotics (DDA), insufficient wind deflection in winter, and male gender. For administration of antibiotics to all calves of the cohort, a DDA of 14-21 was associated with a decreased risk for CL compared to a DDA of 7-13 days.

Inhibition of Fas-associated death domain-containing protein (FADD) protects against myocardial ischemia/reperfusion injury in a heart failure mouse model

AIM As technological interventions treating acute myocardial infarction (MI) improve, post-ischemic heart failure increasingly threatens patient health. The aim of the current study was to test whether FADD could be a potential target of gene therapy in the treatment of heart failure. METHODS Cardiomyocyte-specific FADD knockout mice along with non-transgenic littermates (NLC) were subjected to 30 minutes myocardial ischemia followed by 7 days of reperfusion or 6 weeks of permanent myocardial ischemia via the ligation of left main descending coronary artery. Cardiac function were evaluated by echocardiography and left ventricular (LV) catheterization and cardiomyocyte death was measured by Evans blue-TTC staining, TUNEL staining, and caspase-3, -8, and -9 activities. In vitro, H9C2 cells transfected with ether scramble siRNA or FADD siRNA were stressed with chelerythrin for 30 min and cleaved caspase-3 was assessed. RESULTS FADD expression was significantly decreased in FADD knockout mice compared to NLC. Ischemia/reperfusion (I/R) upregulated FADD expression in NLC mice, but not in FADD knockout mice at the early time. FADD deletion significantly attenuated I/R-induced cardiac dysfunction, decreased myocardial necrosis, and inhibited cardiomyocyte apoptosis. Furthermore, in 6 weeks long term permanent ischemia model, FADD deletion significantly reduced the infarct size (from 41.20 ± 3.90% in NLC to 26.83 ± 4.17% in FADD deletion), attenuated myocardial remodeling, improved cardiac function and improved survival. In vitro, FADD knockdown significantly reduced chelerythrin-induced the level of cleaved caspase-3. CONCLUSION Taken together, our results suggest FADD plays a critical role in post-ischemic heart failure. Inhibition of FADD retards heart failure progression. Our data supports the further investigation of FADD as a potential target for genetic manipulation in the treatment of heart failure.