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PubMed2001

Death rates and causes of death in cohorts of serum hepatitis patients followed up for more than 20 years.

A cohort of 214 drug addicts with serum hepatitis and a cohort of 193 hepatitis patients without drug addiction were examined in respect of death rates, causes of death and a number of risk factors for reduced survival. The death rate was significantly higher among the drug addicts than among non-addicts. The annual mortality rate was 1.5% in the drug addict group and 0.7% in the non-addict group. The highest relative risk of death was 860 for female drug addicts in age group 15-24 compared to females of the same age in the general population. The most prevalent cause of death in the drug addict group was drug overdose (53%), whereas in the other group 66% died from various somatic diseases. Hepatitis or complications of viral hepatitis played no role as cause of death among the drug addicts, and infections as a whole were also responsible for very few deaths. For male drug addicts, imprisonment before admission and leaving hospital without the doctors' permission were risk factors for early death.

Adolescent↗
PubMed2007

Cancer and the threat of death: the cognitive dynamics of death-thought suppression and its impact on behavioral health intentions.

Five studies examined the cognitive association between thoughts of cancer and thoughts of death and their implication for screening intentions. Study 1 found that explicit contemplation of cancer did not increase death-thought accessibility. In support of the hypothesis that this reflects suppression of death-related thoughts, Study 2 found that individuals who thought about cancer exhibited elevated death-thought accessibility under high cognitive load, and Study 3 demonstrated that subliminal primes of the word cancer led to increased death-thought accessibility. Study 4 revealed lower levels of death-thought accessibility when perceived vulnerability to cancer was high, once again suggesting suppression of death-related thoughts in response to conscious threats associated with cancer. Study 5 extended the analysis by finding that after cancer salience, high cognitive load, which presumably disrupts suppression of the association between cancer and death, decreased cancer-related self-exam intentions. Theoretical and practical implications for understanding terror management, priming and suppression, and responses to cancer are discussed.

Analysis of Variance↗
PubMed2001

The kiss of death: promises and failures of death receptors and ligands in cancer therapy.

Death receptors and their ligands exert important regulatory functions in the maintenance of tissue homeostasis and the physiological regulation of programmed cell death. Currently, six different death receptors are known including tumor necrosis factor (TNF) receptor-1, CD95 (Fas/APO-1), TNF receptor-related apoptosis-mediating protein (TRAMP), TNF-related apoptosis-inducing ligand (TRAIL) receptor-1 and -2, and death receptor-6 (DR6). The signaling pathways by which these receptors induce apoptosis are similar and rely on oligomerization of the receptor by death ligand binding, recruitment of an adapter protein through homophilic interaction of cytoplasmic domains, and subsequent activation of an inducer caspase which initiates execution of the cell death programme. The ability of these receptors and their ligands to kill malignant cells was discovered early and helped to coin the term 'tumor necrosis factor' for the first identified death ligand. This review summarizes the current and rapidly expanding knowledge about the signaling pathways triggered by death receptor/ligand systems, their potency in experimental cancer therapy, and their therapeutic limitations, especially regarding their toxicity for non-malignant cells.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Death and dying in contemporary society: an evaluation of current attitudes and the rituals associated with death and dying and their relevance to recent understandings of health and healing.

This paper develops a model which is intended to help nurses and other health professionals in the understanding of contemporary views regarding death and dying and the associated issues of health and healing. The author contends that in the first half of the 20th century, society lost sight of the importance of rituals associated with death and dying and of the need for appropriate death education. Consequently patients and professionals alike found themselves unable to cope with the inevitability of death. Fear supplanted hope, and the health and well-being of society was deleteriously influenced. During the second half of the century, there has been a proliferation of thanatology research and literature. Health professionals are realizing the inadequacy of their knowledge of an issue which fundamentally and unavoidably affects everyone including themselves. The holistic approach to health care has been recognized by many researchers as being essential to health and healing, and therefore death and dying have to be addressed. Often nurses are the professionals left to deal with the patients' grief and anger, and it is therefore critical that they are conversant with the contemporary parallel issues of death and dying and health and healing. The author also firmly believes that before nurses can help people to overcome the fear of death and to optimize their lives, it is essential to examine the traditions of other cultures as well as personal experiences and coping mechanisms, before an understanding of other people's fears and beliefs concerning death and dying can be reached.

Attitude to Death↗
PubMed2000

Cell death induction by CTL: perforin/granzyme B system dominantly acts for cell death induction in human hepatocellular carcinoma cells.

Cell death induction by cytotoxic T lymphocytes (CTLs) is an important thesis for the understanding of tumor immunotherapy. In the current study we investigated the molecular machinery of CTL-induced cell death in human hepatocellular carcinoma cell lines (HCC lines). CTLs prepared from human peripheral blood induced cell death in all tested HCC lines. As the CTL-induced death system, the effectiveness of Fas ligand/Fas and/or Perforin/Granzyme B systems has been suggested, whereas cell death induction by CTLs was shown independently on Fas expression in the current study. Using various tetrapeptide inhibitors for caspase and its associated factor, we additionally demonstrated that inhibitors for caspase 3 (Ac-DEVD-CHO) and caspase 8/granzyme B (Ac-IETD-CHO) suppressed CTL-induced cell death, but an inhibitor for Fas-activated serine proteinase, which acts for the caspase 3 activator, did not, suggesting that CTL-induced cell death was initiated by the Perforin/Granzyme B system, rather than the Fas ligand/Fas system. On the basis of our current results, we report here that the Perforin/Granzyme B system acts dominantly for the cell death induction of HCC lines.

Animals↗
PubMed1991

Will a course on death and dying lower students' death and dying anxiety?

This course describes a 7-week, one-and-one-half-hour per week course on Death and Dying and examines its impact on medical students' attitudes. The 30 participants were tested on attitudes about death and dying pre- and post-course. The pre- and post-course fears about death and dying were measured with the 32-item Collett-Lester Death Anxiety Scale, which measures fear of death and the dying process as these apply to self and others. The Semantic Differential technique was used to measure the pre- and post-course attitudes toward "treating the dying patient" and "dealing with the dying patient's family." There was a decrease in anxiety about death and dying when the posttest was compared with the pretest on the anxiety scales, with death of self and death of others reaching significance (p = .04 and .04). There was a decrease in anxiety scores on the Semantic Differential on treating the dying patient and dealing with the dying patient's family (p = less than .001 for both).

Attitude to Death↗
PubMed2001

Personal meanings of death in older adults and young adults in relation to their fears of death.

Age and gender differences in personal meanings of death have been noted from late childhood to middle adulthood but have been little studied in older adults, for whom death is less remote. Also, such meanings have not been related to their fears of death. Groups of 78 young adults (aged 19-29) and 68 older adults (aged 70-97) were compared on the Personal Meanings of Death (Extinction, After-life, Motivator, Legacy) and on 4 Multidimensional Fear of Death (MFODS) subscales. Analysis of variance indicated that the young scored higher (p <.05) than older adults on death as Motivator and on 3 MFODS subscales. Women scored higher than men on Motivator and fear of the dying process, but men had greater fear of the unknown. Death meanings After-life and Extinction were most strongly correlated with fear of death for both young and old. Further analysis revealed age differences within the older adult group.

Adult↗
PubMed2003

Place of death: analysis of cancer deaths in part of North West England.

BACKGROUND: Relatively little work of a detailed geographical nature has been undertaken on the distribution of place of death. In particular, given evidence that most cancer patients would prefer to die at home there is a need to examine the extent to which this preference is met differentially from place to place. METHODS: Using data on cancer deaths for a single Health Authority in North West England we conducted both small area and individual analyses of place of death, using binomial and binary logistic regression models, respectively. RESULTS: Results from the small area analysis show that in more deprived areas cancer patients are more likely to die in hospital or hospice, and less likely to die at home, but that the effect disappears for home and hospice deaths once other factors are controlled for. At the individual level, the probability of death at home decreases among those living in deprived areas, whereas the probability of death in hospital increases as area deprivation increases. Age, gender, type of cancer, and proximity to hospital or hospice all have some effect on the probability of dying in a particular setting. CONCLUSION: There is significant place-to-place variation in place of death among cancer patients in part of North West England. However, studies of place of death among cancer patients need to consider the full range of settings and, if examining the impact of deprivation or social class, need to adjust for other factors, including proximity to different settings.

Death↗
PubMed2004

Is death-feigning adaptive? Heritable variation in fitness difference of death-feigning behaviour.

The adaptation of death-feigning (thanatosis), a subject that has been overlooked in evolutionary biology, was inferred in a model prey-and-predator system. We studied phenotypic variation among individuals, fitness differences, and the inheritance of death-feigning behaviour in the red flour beetle, Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae). Two-way artificial selections for the duration of death-feigning, over 10 generations, showed a clear direct response in the trait and a correlated response in the frequency of death-feigning, thus indicating variation and inheritance of death-feigning behaviour. A comparison of the two selected strains with divergent frequencies of death-feigning showed a significant difference in the fitness for survival when a model predator, a female Adanson jumper spider, Hasarius adansoni Audouin (Araneomophae: Salticidae), was presented to the beetles. The frequency of predation was lower among beetles from strains selected for long-duration than among those for short-duration death-feigning. The results indicate the possibility of the evolution of death-feigning under natural selection.

Adaptation, Biological↗
PubMed2004

A critical review of the causes of death among post-mortem toxicological investigations: analysis of 34 buprenorphine-associated and 35 methadone-associated deaths.

AIMS: To assess the trends in the number, mortality and the nature of forensic cases involving toxicological detection of buprenorphine or methadone among toxicological investigations performed in Paris from June 1997 to June 2002. DESIGN: Retrospective, 5 year study with review of premortem data, autopsy, police reports, hospital data, and post-mortem toxicological analyses. SETTING AND PARTICIPANTS: 34 forensic cases of buprenorphine and 35 forensic cases of methadone detection among 1600 toxicological investigations performed at the Laboratory of Toxicology in the Medical Examiner's Office in Paris. MEASUREMENTS AND RESULTS: Therapeutic, toxic or lethal drug concentrations were defined based upon the results of blood analyses and the published literature. Drug concentrations were cross-referenced with other available ante- and post-mortem data. Subsequently, we classified a 'clear responsibility', 'possible responsibility' or 'not causative' role for buprenorphine or methadone in the death process, or 'no explanation of death'. Buprenorphine and methadone can be regarded as being directly implicated in, respectively, four of 34 death cases (12%) and three of 35 death cases (9%), and their participation in the lethal process is strongly plausible in eight (buprenorphine) and 11 (methadone) additional deaths. CONCLUSIONS: Analysis of causes of death reveals the difficulties in determining the role of substitution drugs in the death process, as many other factors may be involved, including circumstances surrounding death, past history, differential selection of subjects into either substitution modality and concomitant intake of other drugs (especially benzodiazepines and neuroleptics). The potential for synergistic or additive actions by other isolated molecules-particularly opioids, benzodiazepines, other psychotropes and alcohol-must be also considered.

Adult↗
PubMed2005

Death brokering: constructing culturally appropriate deaths.

Death brokering refers to the activities of medical authorities to render individual deaths culturally meaningful. Social scientists and others agree that mortality provokes existential ambiguity in modern life requiring cultural coping mechanisms. In contemporary Western societies, medical professionals have sequestered the dying in institutions, and have classified the causes of death to explain suspicious death. Over the last decades, the institutionalisation of the dying process has been challenged by social movements and the sudden onset of some deaths while forensic medicine has struggled for professional legitimacy in the borderland between mainstream medicine and the legal system. I argue that medical death brokering persists in spite of challenges because medical experts offer increasingly flexible cultural scripts to render the end-of-life socially meaningful while accentuating death's existential ambiguity. Medical professionals help create the ambiguity they promise to resolve, reinforcing the cultural need for more expert death brokering.

Adaptation, Psychological↗
PubMed1985

Effect of a brief instructional unit in death education on the death attitudes of prospective elementary school teachers.

The present study determined if there would be a significant change in the attitudes of prospective elementary school teachers toward death after two, one- and-one-half hour instructional units of death education that were incorporated into an elementary health education methods and content class (experimental group). Control groups consisted of similar students who did not receive death education, but were enrolled in the elementary health education methods and content class (control group I) and another group of students who were not in elementary education, but were enrolled in a basic home economics class (control group II). The Templer Death Anxiety Scale and a scale developed by the author to measure attitudes toward death education for young children were administered to the three groups during pretest and posttest sessions two and 10 weeks after instruction. Validity and reliability for the author's scale was determined by various experimental procedures. Several different resources were used in the education process. The experimental group had significantly less fear of death and felt more comfortable discussing death with children than did the two control groups. The results suggest that brief units of death education are effective in changing the attitudes of future elementary teachers.

Adult↗
PubMed1992

Susceptibility to cell death is a dominant phenotype: triggering of activation-driven T-cell death independent of the T-cell antigen receptor complex.

The failure of Thy-1 and Ly-6 to trigger interleukin-2 production in the absence of surface T-cell antigen receptor complex (TCR) expression has been interpreted to suggest that functional signalling via these phosphatidylinositol-linked alternative activation molecules is dependent on the TCR. We find, in contrast, that stimulation of T cells via Thy-1 or Ly-6 in the absence of TCR expression does trigger a biological response, the cell suicide process of activation-driven cell death. Activation-driven cell death is a process of physiological cell death that likely represents the mechanism of negative selection of T cells. The absence of the TCR further reveals that signalling leading to activation-driven cell death and to lymphokine production are distinct and dissociable. In turn, the ability of alternative activation molecules to function in the absence of the TCR raises another issue: why immature T cells, thymomas, and hybrids fail to undergo activation-driven cell death in response to stimulation via Thy-1 and Ly-6. One possibility is that these activation molecules on immature T cells are defective. Alternatively, susceptibility to activation-driven cell death may be developmentally regulated by TCR-independent factors. We have explored these possibilities with somatic cell hybrids between mature and immature T cells, in which Thy-1 and Ly-6 are contributed exclusively by the immature partner. The hybrid cells exhibit sensitivity to activation-driven cell death triggered via Thy-1 and Ly-6. Thus, the Thy-1 and Ly-6 molecules of the immature T cells can function in a permissive environment. Moreover, with regard to susceptibility to Thy-1 and Ly-6 molecules of the immature T cells can function in a permissive environment. Moreover, with regard to susceptibility to Thy-1 and Ly-6 triggering, the mature phenotype of sensitivity to cell death is genetically dominant.

Animals↗
PubMed1985

Ischaemic heart disease and prodromes of sudden cardiac death. Is it possible to identify high risk groups for sudden cardiac death?

A study was carried out to determine the incidence of sudden cardiac death in a well defined population in relation to prodromes, medical history, and previous medical consultations before sudden cardiac death. In Frederiksborg county, Denmark (population 332 000), of 1309 consecutive deaths in a six month period, 166 were due to sudden cardiac death; among men aged 50-69, 22% of all deaths were due to sudden cardiac death. The incidence per 1000 population per year by age group (less than 50, 50-69, greater than or equal to 70 years) was 0.19, 3.6, 11.4 in men and 0.12, 1.0, and 6.4 in women. The increasing incidence with age was significant. Ischaemic heart disease or hypertension had been recorded in 75% (124/166) of patients. Prodromes were reported in 54% (38/71) of patients with angina, and in 26% (25/95) without. Nineteen per cent (32/166) had neither prodromes nor overt heart disease. Forty six per cent of patients with known ischaemic heart disease and 24% without had consulted a doctor less than four weeks before death. Eight per cent had had a myocardial infarction within a year of death.

Adult↗
PubMed2000

Sudden unexpected death in epilepsy: a series of witnessed deaths.

OBJECTIVES: Sudden unexpected death in epilepsy (SUDEP) represents a significant category of mortality in the population with chronic epilepsy. A consistent feature is that most of these deaths are unwitnessed. The aim was to identify witnessed deaths, examine the circumstances, and relate these findings to the proposed mechanisms for SUDEP. METHODS: During the course of case ascertainment for a control study on SUDEP, witnessed deaths were identified and the circumstances examined in detail. Cases were notified by coroners, neurologists, and bereaved families. The findings were related to the proposed mechanisms for SUDEP which include central and obstructive apnoea and cardiac arrhythmia. RESULTS: One hundred and thirty five SUDEP cases have been identified to date, of which 15 were witnessed deaths. Twelve deaths were associated with convulsive seizures, one collapse occurred 5 minutes after a generalised seizure, another collapse occurred after an aura and one patient died while in a probable post ictal state. Witnesses reported that 12 of the 15 cases experienced respiratory difficulty. CONCLUSIONS: Most sudden epilepsy deaths are unwitnessed. Where witnessed most occur in association with a seizure and respiratory compromise is a prominent feature. Positioning or stimulation of respiration may be important in the prevention of these deaths.

Adolescent↗
PubMed2006

Changing HIV infection-related mortality rate and causes of death among persons with HIV infection before and after the introduction of highly active antiretroviral therapy: analysis of all HIV-related deaths in Barbados, 1997-2005.

OBJECTIVES: To compare the trends in death rates and the causes of deaths before and after the introduction of highly active antiretroviral therapy. METHODS: This is a retrospective study based on chart review of all HIV-related deaths between January 1997 and December 2005. RESULTS: The HIV-specific death rate declined from 34.12 per 100,000 adult population during 1997-1999 to 17.21 per 100,000 adult population during 2003-2005 when highly active anti-retroviral therapy was available. The proportion of all HIV-related deaths among persons newly diagnosed with HIV during the terminal hospitalization decreased from 93% during 1997-1999 to 28% during 2003-2005. Opportunistic infection was at least one of the causes of death in nearly half of all cases. CONCLUSIONS: Although, the HIV-specific death rates have declined significantly since the introduction of highly active antiretroviral therapy, HIV infection continues to contribute to the premature deaths among adults, mainly because of the late presentation.

AIDS-Related Opportunistic Infections↗
PubMed2005

Cancer-specific toxicity of apoptin is independent of death receptors but involves the loss of mitochondrial membrane potential and the release of mitochondrial cell-death mediators by a Nur77-dependent pathway.

Apoptin, a small proline-rich protein derived from the chicken anaemia virus, induces cell death selectively in cancer cells. The signalling pathways of apoptin-induced, cancer cell-selective apoptosis are not well understood. Here, we demonstrate that apoptin triggers apoptosis by activating the mitochondrial/intrinsic pathway, and that it acts independently of the death receptor/extrinsic pathway. Jurkat cells deficient in either FADD or caspase-8 (which are both necessary for the extrinsic pathway) were equally as sensitive to apoptin as their parental clones. This demonstrates that apoptin is likely to act through the mitochondrial death pathway. Apoptin treatment causes a loss of mitochondrial membrane potential, and release of the mitochondrial proteins cytochrome c and apoptosis-inducing factor. Apoptin-induced cell death is counteracted by the anti-apoptotic Bcl-2 family members, Bcl-2 itself and Bcl-XL, as shown in Jurkat leukaemia cells. In addition, we describe the processing and activation of caspase-3. By contrast, cleavage of caspase-8, which is predominantly triggered by the death receptor pathway, is not observed. Furthermore, apoptin triggers the cytoplasmic translocation of Nur77, and the inhibition of Nur77 expression by siRNA significantly protects MCF7 cells from apoptin-triggered cell death. Thus, our data indicate that the apoptin death signal(s) ultimately converges at the mitochondria, and that it acts independently of the death receptor pathway.

Adaptor Proteins, Signal Transducing↗
PubMed1988

Sudden death in young soldiers. High incidence of syncope prior to death.

During the years 1974 to 1986, 44 young soldiers (mean age 21 +/- 3 years) died suddenly and unexpectedly in the Israel Defense Forces. Cardiac causes accounted for 54 percent of deaths; neurologic causes, 14 percent of deaths; other diseases, 9 percent; and in 23 percent, cause of death was unknown. Although most sudden deaths are considered unpredictable, preceding symptoms were reported in more than one half of the patients. We found that syncope had occurred in 23 percent of cases, chest pain in 11 percent, and febrile disease in 16 percent. Exercise-associated syncope occurred in 16 percent and exercise-associated death occurred in most (86 percent) of those cases. Diagnosis at the time of the preceding symptoms failed to predict the fatal diseases in most cases. Our report points out the high incidence of syncope prior death in young soldiers with sudden death. Although further prospective controlled studies are needed in order to confirm that impression, we suggest that the possibility of syncope followed by sudden death should be kept in mind while evaluating young patients presenting with exercise-associated syncope.

Adolescent↗