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[Reevaluation of heart disease deaths on death certificates and trends for ischemic heart disease mortality during the last five years in Oita city].

To evaluate heart disease deaths and clarify trends for ischemic heart disease (IHD) mortality during the last five years in Oita City, we reevaluated causes of death on death certificates. In 1993, there were 253,000 people aged 25-74 in Oita City. In this population age group, there were 1,996 deaths from January 1992 through December 1993. Our subjects were 982 deaths recorded as caused by heart disease and IHD related diseases. Subjects were reevaluated on the basis of physician's interview, clinical records and police records. This IHD reevaluation was conducted by the WHO MONICA criteria. The death certificates identified 321 heart disease deaths, of which there were 80 (24.9%) acute myocardial infarctions (AMI), 22 (6.9%) other IHD, 180 (56.1%) heart failures, and 39 (12.1%) other heart diseases. The remaining 61 deaths were caused by other diseases. After reevaluation, 40 'definite' AMI and 60 'possible' AMI were recognized through the MONICA criteria, 86 sudden deaths (SD) which were defined as, 'death within 24 hours of the onset of acute symptoms and without clear signs suggesting what disease was the cause,' were also classified. Assuming that 50% of SD were due to IHD, according to some postmortem autopsy studies, aged-standardized IHD mortality per 100,000 for males was 38.3 per year and for females 17.3 per year in this period. Both mortality rates, 31% for males and 38% for females, were higher than IHD mortality statistics. Moreover, in comparison with IHD mortality estimated by reevaluation of heart disease in Oita City in 1987-88, age-standardized IHD mortality per 100,000 for males has remained basically stable, increasing from 37.8 to 38.4 during the last five years. On the other hand, mortality for females has increased from 11.2 to 17.3. Our results suggest that mortality from IHD actually was about 30% more than mortality statistics, and does not show a declining trend as mortality statistics have stated.

Adult↗

Prion protein prevents human breast carcinoma cell line from tumor necrosis factor alpha-induced cell death.

To define genetic determinants of tumor cell resistance to the cytotoxic action of tumor necrosis factor alpha (TNF), we have applied cDNA microarrays to a human breast carcinoma TNF-sensitive MCF7 cell line and its established TNF-resistant clone. Of a total of 5760 samples of cDNA examined, 3.6% were found to be differentially expressed in TNF-resistant 1001 cells as compared with TNF-sensitive MCF7 cells. On the basis of available literature data, the striking finding is the association of some differentially expressed genes involved in the phosphatidylinositol-3-kinase/Akt signaling pathway. More notably, we found that the PRNP gene coding for the cellular prion protein (PrP(c)), was 17-fold overexpressed in the 1001 cell line as compared with the MCF7 cell line. This differential expression was confirmed at the cell surface by immunostaining that indicated that PrP(c) is overexpressed at both mRNA and protein levels in the TNF-resistant derivative. Using recombinant adenoviruses expressing the human PrP(c,) our data demonstrate that PrP(c) overexpression converted TNF-sensitive MCF7 cells into TNF-resistant cells, at least in part, by a mechanism involving alteration of cytochrome c release from mitochondria and nuclear condensation.

Breast Neoplasms↗

Appropriate death: college students' preferences vs. actuarial projections.

Appropriate death was defined as the kind of death a person might choose for himself/herself, if given a choice. Ss were 382 college students who stated their preferences for (a) age at time of death; (b) cause of death; (c) site of death; and (d) means of disposal of remains. Preferences were compared with national actuarial projections. The preferred average life expectancy for women was lower than the national average life expectancy (p less than .001). Natural causes and accidents were oversubscribed, while cardiovascular ailments and cancer were undersubscribed as causes of death. A non-institutional site for death was preferred by 91.3% of the Ss; 39% of all deaths now occur outside an institution. Traditional burial underground was the choice of just more than half the sample, but a slight trend toward less traditional means of disposal of remains was noted over the five semesters of the study.

Adult↗

Maternal mortality: only 42 days?

OBJECTIVE: A maternal death is defined by WHO as 'the death of a woman while pregnant or within 42 days of termination of pregnancy em leader '. The origin of the 42 days is no longer clear. In developing countries, the burden imposed by pregnancy and birth on a woman's body may extend beyond 42 days as pregnancy-related anaemia can persist for longer and vaginal haemorrhaging and risk of infections are not necessarily over after six weeks. We therefore examined duration of excess mortality after delivery in rural Guinea-Bissau. DESIGN: In a prospective cohort study, we followed 15,844 women of childbearing age with biannual visits over a period of six years, resulting in a total of 60,192 person-years-at-risk. To establish cause and timing in relation to termination of pregnancy, verbal autopsy was carried out for all deaths. Mortality rates were calculated for short time intervals after each delivery or miscarriage. RESULTS: During the observation period we registered 14,257 pregnancies and 350 deaths. One hundred and ninety-four deaths followed termination of a registered pregnancy and thus were eligible for the analysis. Eighty-two deaths occurred during the first 42 days after delivery/miscarriage. A further 16 women died in the period from 43 to 91 days after parturition, 16 between 92 and 182 days and 18 between 183 and 365 days after delivery. Compared with baseline mortality 7-12 months after delivery, women who had recently delivered had 15.9 times higher mortality (95% CI 9.8-27.4). From days 43 to 91 the mortality was still significantly elevated (RR = 2.8 [1.4-5.4]). CONCLUSION: Where living conditions are harsh, pregnancy and delivery affect the health of the woman for more than 42 days. Using the WHO definition may result in an under-estimation of the pregnancy-related part of the reproductive age mortality. Extending the definition of maternal death to include all deaths within three months of delivery may increase current estimates of maternal mortality by 10-15%.

Abortion, Spontaneous↗

Autophagy gene disruption reveals a non-vacuolar cell death pathway in Dictyostelium.

Types of cell death include apoptosis, necrosis, and autophagic cell death. The latter can be defined as death of cells containing autophagosomes, autophagic bodies, and/or vacuoles. Are autophagy and vacuolization causes, consequences, or side effects in cell death with autophagy? Would control of autophagy suffice to control this type of cell death? We disrupted the atg1 autophagy gene in Dictyostelium discoideum, a genetically tractable model for developmental autophagic vacuolar cell death. The procedure that induced autophagy, vacuolization, and death in wild-type cells led in atg1 mutant cells to impaired autophagy and to no vacuolization, demonstrating that atg1 is required for vacuolization. Unexpectedly, however, cell death still took place, with a non-vacuolar and centrally condensed morphology. Thus, a cell death mechanism that does not require vacuolization can operate in this cell death model showing conspicuous vacuolization. The revelation of non-vacuolar cell death in this protist by autophagy gene disruption is reminiscent of caspase inhibition revealing necrotic cell death in animal cells. Thus, hidden alternative cell death pathways may be found across kingdoms and for diverse types of cell death.

Animals↗

Stroke in Asia: an epidemiological consideration.

Although the study of the epidemiology of stroke in developed Western countries (as judged from the number of relevant articles published in international medical journals) is extensive, in Asian countries it has been comparatively limited (with the exception of Japan). Many of the studies from Asian countries also appear to be deficient, thus making comparison between the countries difficult. In addition, many of these studies are believed to be published in local journals not usually cited and difficult to retrieve from, and relevant and retrievable data from many developing countries often show considerable time lapse, making a meaningful comparison between countries even more difficult. In Thailand, Public Health Statistics show that stroke has been on the increase. Taken as an example, the death rate from cerebrovascular disease (CVD) was 3.7/100,000 in 1950, rising to 6.7/100,000 in 1970, and to 11.8/100,000 in 1983. In 1984, there were 9,414 cases of CVD admitted to hospitals in Thailand. The incidence (in patients) increased from 12.7/100,000 in 1981 to 18.7/100,000 in 1984. Since 1957, the mortality rate has been steadily increasing, from approximately 1/100,000 to approximately 6/10,000. In a survey taken in 1983 of a medium-size community in Bangkok, it was found that the prevalence of CVD was 6.9/1,000. The same Public Health Statistics also showed that the rate of immediate death after stroke (which is defined as death within 4 weeks after the onset) from nonembolic cerebral infarction, cerebral embolism, and cerebral hemorrhage was reported to be 19.5, 37, and 85% respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Asia↗

Quantifying organ donation rates by donation service area.

Previous measures of OPO performance based on population counts have been deemed inadequate, and the need for new methods has been widely accepted. This article explains recent developments in OPO performance evaluation methodology, including those developed by the SRTR. As a replacement for the previously established measure of OPO performance--donors per million population--using eligible deaths as a national metric has yielded promising results for understanding variations in donation rates among the donation service areas assigned to each OPO. A major improvement uses "notifiable deaths" as a denominator describing a standardized maximal pool of potential donors. Notifiable deaths are defined as in-hospital deaths among ages 70 years and under, excluding certain diagnosis codes related to infections, cancers, etc. A most proximal denominator for determining donation rates is "eligible deaths," which includes only those deaths meeting the criteria for organ donation upon initial assessment. Neither measure is based on the population of a geographic unit, but on restricted upper limits of deaths that could be potential donors in any one locale (e.g., hospital or OPO). The inherent strengths and weaknesses of metrics such as donors per eligible deaths, donors per notifiable deaths, and number of organs per donor are discussed in detail.

Humans↗

Trends in the place of death of cancer patients, 1992-1997.

BACKGROUND: Although many patients with cancer would prefer to die at home, most die in hospital. We carried out a study to describe the yearly trends in the place of death between 1992 and 1997 and to determine predictors of out-of-hospital death for adults with cancer in Nova Scotia. METHODS: In this population-based study, we linked administrative health data from 2 databases - the Nova Scotia Cancer Centre Oncology Patient Information System and the Queen Elizabeth II Health Sciences Centre Palliative Care Program - for all adults in Nova Scotia who died of cancer from 1992 to 1997. We also used grouped neighbourhood income information from the 1996 Canadian census. Death out of hospital was defined as death in any location other than an acute care hospital facility. We used logistic regression analysis to identify the odds of dying out of hospital over time and to identify factors predictive of out-of-hospital death. RESULTS: A total of 14 037 adults died of cancer during the study period. The data for 101 people were excluded because of missing information regarding place of death. Of the remaining 13 936 people, 10 266 (73.7%) died in hospital and 3670 (26.3%) died out of hospital. Over the study period the proportion of people who died out of hospital rose by 52%, from 19.8% (433/2182) in 1992 to 30.2% (713/2359) in 1997. Predictors associated with out-of-hospital death included year of death (for 1997 v. 1992, adjusted odds ratio [OR] 1.8, 95% confidence interval [CI] 1.5-2.0), female sex (adjusted OR 1.2, 95% CI 1.1-1.3), age (for > or = 85 v. 18-44 years, adjusted OR 2.2, 95% CI 1.7-2.8), length of survival (for 61-120 v. < or =60 days, adjusted OR 2.2, 95% CI 1.8-2.6; for 121-180 v. < or =60 days, adjusted OR 2.5, 95% CI 2.2-2.8), having received palliative radiation (adjusted OR 0.8, 95% CI 0.7-0.9) and region of death (Cape Breton v. Halifax, adjusted OR 0.5, 95% CI 0.5-0.6). Among Halifax residents, registration in the Palliative Care Program was also a significant predictor of out-of-hospital death (adjusted OR 1.4, 95% CI 1.2-1.7). Tumour group, neighbourhood income and residence (urban v. rural) were not predictive of out-of-hospital death in multivariate analysis. INTERPRETATION: Over time, more patients with cancer, especially women, elderly people and people with longer survival after diagnosis, died outside of hospital in Nova Scotia.

Adolescent↗

Risk factors in oral and oropharyngeal squamous cell carcinoma: a population-based case-control study in southern Sweden.

In the year 2002, about 275,000 inhabitants around the world developed oral cancer and over half of them will die of their disease within 5 years. Oral and oropharyngeal squamous cell carcinoma (OOSCC) accounts for about 1% of all cancers in Sweden - which is low compared to the incidence on the Indian subcontinent and in other parts of Asia, where it is one of the most common forms of cancer. The incidence in Sweden is increasing, however. The study comprised 80% (132/165) of all consecutive cases living in the Southern Healthcare Region, born in Sweden and without previous cancer diagnosis (except skin cancer), who were diagnosed with OOSCC during the period September 2000 to January 2004. Using the Swedish Population Register, 396 cancer-free controls were identified and matched by age, gender and county. Of these individuals, 320 (81%) agreed to take part in the study. Cases and controls were subjected to a standardised interview, identical oral examinations including panoramic radiographs, and cell sampling for human papillomavirus (HPV) analysis. In total 128 patients with planned curative treatment were followed for a median time of 22 months (range 0 - 36). The aims were to assess different potential risk factors in OOSCC such as oral hygiene, dental status, oral mucosal lesions, alcohol and tobacco use, virus infection, and some related to lifestyle. A further aim was to assess the influence of these factors on recurrence or occurrence of a new second primary tumour (SPT) of squamous cell carcinoma. In multivariate analysis average oral hygiene (OR 2.0; 95% CI 1.1-3.6) and poor oral hygiene (OR 5.3; 95% CI 2.5-11.3), more than 5 defective teeth (OR 3.1; 95% CI 1.2-8.2) and more than 20 teeth missing (OR 3.4; 95% CI 1.4-8.5), as well as defective or malfunctioning complete dentures (OR 3.8; 95 % CI 1.3-11.4) were identified as significant risk factors for development of OOSCC. Regular dental care reduced the risk of OOSCC (OR 0.4; 95% CI 0.2-0.6). The cases reported a higher consumption of alcohol than the controls. More than 350 g of alcohol per week (OR 2.6; 95% CI 1.3-5.4) and 11-20 cigarettes per day (OR 2.4; 95% CI 1.3-4.1) were dose-dependent risk factors. The results showed a tendency for women to have a greater risk (OR 1.8) than men at any given level of tobacco consumption. There was no increased risk of OOSCC among users of Swedish moist snuff. There was a significant relationship between high-risk human papillomavirus (HPV) infection and OOSCC (OR 63; 95% CI 14-280). Forty-seven of the cases (36%) were high-risk HPV infected and 7 (5.3%) were low-risk HPV infected in the specimens collected from the oral cavity. The corresponding figures for the controls were 3 (0.94%) and 13 (4.1%), respectively. The high-risk HPV types found in the oral cavity were the same types as observed in cervical cancer. Tumour stage was associated with both higher relative rate (RR) of recurrence or second primary tumour (SPT) of squamous cell carcinoma, and death in intercurrent diseases (DICD), defined as death before the occurrence of recurrence or SPT. High-risk HPV infected patients had an almost threefold increased RR of recurrence/SPT, but seemingly a lower RR of DICD compared to high-risk negative cases. Patients with tonsillar carcinoma had a significantly higher cause-specific RR of recurrence/SPT (RR 2.06; CI 0.99 - 4.28) compared to patients with OSCC of other sites. High alcohol consumption was associated with a high RR of recurrence/SPT, but not with DICD. There was no increased RR of recurrence/SPT related to smoking, but an association between smoking and DICD. In conclusion, the results in this study confirm that both smoking tobacco and alcohol consumption are risk factors for OOSCC. The use of Swedish moist snuff had no effect on the risk. Independent risk factors identified are poor oral hygiene, inadequate dental status and malfunctioning complete dentures. Regular dental check-ups are a preventive factor. Among other possible risk factors studied, high-risk HPV infection appears to be the strongest. High-risk HPV infection increases the cause-specific RR of recurrence or SPT. Tumour stage influences the rate of recurrence/SPT.

Adult↗

Maternal mortality in British Columbia in 1971-86.

We reviewed the 56 maternal deaths in British Columbia in 1971-78 and 1979-86 identified through the provincial Ministry of Health and compared the findings with data for the two preceding 8-year periods. The maternal death rate, defined as the number of deaths directly or indirectly related to pregnancy or delivery per 100,000 live births, decreased from 42 in 1955-62 to 5 in 1979-86. In the same interval the number of direct obstetric deaths decreased from 100 to 10 and the number of indirect deaths from 29 to 8. The number of deaths due to abortion decreased from 32 to 1. There was no change in the number of deaths among North American Indians. There was also no change in the number of deaths due to hypertension, most of which were avoidable; these findings have stimulated intensive teaching efforts to increase recognition and improve management of the problem. Review of maternal deaths can help identify deficiencies in the quality of care and can direct measures aimed at further reducing the maternal death rate.

British Columbia↗

A review of sudden infant death syndrome.

This chapter defines sudden infant death syndrome (SIDS) and provides a brief review of the history, current knowledge, pathology, and possible mechanisms of death. The authors conclude with considerations of other selected causes of sudden, unexpected infant death.

Cause of Death↗

[Prognostic value of C-reactive protein and troponin T level in patients with unstable angina pectoris].

OBJECTIVES: The prognosis of unstable angina pectoris may be more accurately predicted by the combination of C-reactive protein (CRP), which is a known inflammation marker, and troponin T (TnT), which is used for risk assessment for the prognosis of acute coronary syndrome. The present study investigated the correlations between pathophysiology and prognosis of severe unstable angina pectoris and CRP and TnT levels. METHODS: The correlation between CRP at admission and the prognosis was studied in 367 patients with severe unstable angina pectoris (Braunwald type II and III) who were admitted to our hospital between January 1998 and December 2000. The in-hospital and long-term prognosis was investigated in TnT-positive patients. In-hospital cardiac events were defined as death, myocardial infarction, heart failure and angina attacks during hospitalization. Long-term cardiac events were defined as death, myocardial infarction, heart failure and recurrence of angina. RESULTS: The incidence of in-hospital cardiac events in all patients was 30.2%. The CRP levels were higher in patients with cardiac events (0.97 +/- 2.67 vs 0.53 +/- 1.29 mg/d/, p = 0.057), but there was no significant difference between the two groups. The incidence of long-term cardiac events was 26.8%. The mean CRP level was significantly higher in patients with cardiac events than in patients without cardiac events (1.17 +/- 1.86 vs 0.43 +/- 1.14 mg/dl, p = 0.098). In TnT-positive patients (TnT > 0.1 ng/ml, 23% of all patients), the incidence of in-hospital cardiac events was 47.6% (p < 0.0001), significantly higher than that in all patients. TnT-positive patients with CRP levels of 0.5 mg/dl or higher (8% of all patients) had a markedly higher incidence of in-hospital cardiac events of 56.7% (p = 0.001) and long-term cardiac events of 46.7% (p = 0.01). CONCLUSIONS: CRP levels were useful in prediction of the long-term prognosis. TnT levels were useful in prediction of in-hospital prognosis. The present study suggested the possibility that the combined use of these biological markers could predict the prognosis of patients with unstable angina at early stage and more accurately.

Angina, Unstable↗

Brain death diagnosis in misleading conditions.

The necessity of defining brain death (BD) arose from technological development in medical science. The definition of this concept had practical consequences and opened the way to organ donation from BD patients. Nowadays, the imbalance between the number of organs available for transplantation and the size of the demand is becoming critical. In most laboratories, a BD diagnosis is made according to precise criteria and in a well-defined process. BD diagnosis should be improved, not only to assure the safety and to preserve the human dignity of the patient, but also in order to increase the rate of organ donation. By analysing some epidemiological parameters in BD diagnosis and organ donation, it appears that BD diagnoses can be made more often and more rapidly if one has a reliable, accurate, and safe confirmatory test, especially under misleading conditions (hypothermia, drugs, metabolic disturbances). In our experience, the use of multimodality evoked potentials (MEPs) to confirm a BD diagnosis has many advantages: MEPs can be rapidly performed at the patient's bedside, assess the brain stem as well as the cerebral cortex, and are innocuous for the patient. Moreover, their insensitivity to the aforementioned misleading factors is sufficient to distinguish BD from clinical and EEG states that mimic BD. They give an immediate diagnosis, and no delay is required in BD confirmation if there is sufficient cause to account for BD. MEPs are a safe, accurate, and reliable tool for confirming a BD diagnosis, and their use can improve the organ donation rate while preserving the safety of the patient.

Brain Death↗

[Effect of all-trans retinoic acid on the newly diagnosed acute promyelocytic leukaemia: our experience].

UNLABELLED: Acute promyelocytic leukaemia (APL) is characterised by the morphology of bias cells (M3), t(15;17) translocation, and coagulopathy combining disseminated intravascular coagulation (DIC) and fibrinolysis. Anthracy cline-cytosine arabinoside (Ara C) intensive chemotherapy yields a complete remission in 50 percent (%) to 80% of newly diagnosed APL patients. Failure to achieve complete remission results in fatal bleeding due to coagulopathy or fatal sepsis during the phase of aplasia. It has been recently shown that all trans retinoic acid (ATRA) selectively differentiates abnormal promyelocytes into mature granulocytes in APL, both in vitro and in vivo, and induced complete remission in 80% to 90% of the newly diagnosed patients. It has also been observed that therapy with ATRA rapidly improved coagulopathy, and induced no aplasia. However, in 30% of patients the treatment with ATRA as a single drug was associated with rapid increase in leukocytes and signs of "ATRA syndrome", which could have fatal outcome. Therefore the European study group initiated in 1991 a multicentre randomised trial comparing chemotherapy with daunorubicin Ara C (chemotherapy group) and ATRA combined to the same chemotherapy (ATRA group) in newly diagnosed APL patients, aged 65 years or less. Results of this study strongly suggest that ATRA should be incorporated in the front line therapy of newly diagnosed APL. The aim of our study was to confirm their results in our newly diagnosed patients. PATIENTS AND METHODS: In our study we had 15 subsequently hospitalised patients with APL in whom diagnosis was made according to MIC classification, and who were treated with ATRA (Vesanoid-Hoffman La Roche) combined with chemotherapy according to the recommendation of the European study groups. The comparison of the effect of ATRA we has evaluated by the outcome of APL in 12 patients who received only combined chemotherapy in induction phase according to the Yu-AML-89 protocol 12 or 01-AM-86 protocol. Both protocols include daunorubicin and Ara C. In all patients MIC classification was performed. Characteristics of the patients included in the study with special emphasis to symptoms at presentation, are given in Table 1. TREATMENT: Patients treated with ATRA plus chemotherapy received daily oral dose of ATRA 45 mg/m2 until the complete remission, or for a maximum of 90 days. After complete remission they received three courses of daunorubicin 60 mg/m2 for 3 days, and Ara C 200 mg/m2 for 7 days. However, course one was added to ATRA on day one of treatment of initial leukocyte counts were greater than 5 x 10(9)/L or rapidly started to increase to above 6 x 10(9)/L or more. Patients treated with chemotherapy received only in induction phase daunorubicin 45 mg/m2 for 4 days and Ara C 200 mg/m for 7 days as well as the intensive platelet support, heparin, fresh frozen plasma in those with bleeding. During the study haemostasis monitoring was performed in all patients. Complete remission was defined according to the criteria of the European study group. Early death was defined as a death during the therapy with ATRA or chemotherapy due to "ATRA syndrome", bleeding, aplasia, or resistant leukaemia. Statistical analysis was performed according to the Kruskal-Wallis test. RESULTS: Relevant haematological and pathobiological characteristics at presentation are shown in Table 2. It can be seen that there were no significant characteristic differences at presentation between ATRA group and chemotherapy group. The effects of the treatment are shown in Table 3. It can be seen that complete remission was achieved in 87% of patients receiving ATRA combined with chemotherapy and only in 42% of patients who received combined chemotherapy. This difference is significant (p < 0.01). Duration of complete remission lasted for 14 months (median) in the patients receiving ATRA while only 5 months (median) in the patients who received combined chemotherapy. Fatal outcome in ATRA group occurred in 13% due to the "ATRA syndrome" and in 58% of the patients treated with combined chemotherapy due to bleeding. Table 4 shows four selected patients from ATRA group in whom complete remission was followed with disappearance of t (15;17), thus providint the evidence of the eradication of clonal abnormalities. It should be emphasised that 2 of 15 patients developed ATRA syndrome during the early phases of the treatment with a feature of cardiorespiratory distress. The therapy with steroid was unsuccessful. Nine of 13 patients in ATRA group had moderate side effects with no necessity to discontinue the therapy. DISCUSSION: Our clinical trial shows for the first time in our county a beneficial effect of ATRA in addition to chemotherapy compared with chemotherapy alone in newly diagnosed APL, thus comfirming the results of the European study group. The only flaw of in our study may come from the fact that the patients included in the study were not randomised and that for the comparison of the ATRA group were used previously treated patients with chemotherapy alone. However, we believe that this flaw has been overcome since uniform diagnostic procedure and particularly MIC classification were performed in all patients. In addition to that, all patients included in the trial were subjected to the analysis of haemostatic status as well as to precise biochemical studies, ECG and abdominal echography. It is interesting to note that in our study, similarity to the European study group, 13% of patients developed "ATRA syndrome". Therefore, it is recommended that further effort should be made in order to prevent this fatal and not yet resolved syndrome.

Adult↗

Early deaths in childhood cancer.

BACKGROUND: Deaths prior to or shortly after the diagnosis of childhood cancer may reflect inadequacies in detection and appropriate referral for care. This study was performed to determine the extent of and factors associated with early death in childhood cancer. PROCEDURE: Patients with of primary cancer, aged <20 years at diagnosis, were identified from the SEER data (n = 23,470) from 1973 to 1995. Early deaths were defined as cases identified by 1) death certificate, 2) autopsy report, or 3) death within 1 month of initial diagnoses (n = 481). Cause of death was determined by ICD-8 and -9 codes. Age at diagnosis, year of diagnosis, morphology, site of disease, race, and gender were evaluated for association with early death. RESULTS: Age <1 year at diagnosis (6.2% early deaths), being diagnosed earlier in the observation period, and a diagnosis of a brain tumor, neuroblastoma, leukemia, or liver tumor were associated with increased early death. Gender and race were not associated with early death. Among the cases for whom the malignant diagnosis was made at the time of death (n = 119), the cause of death was nonmalignant for 36. For 22 of these cases the malignancy was an incidental finding and appeared not to contribute directly to the cause of death. Among these patients, 11 had neuroblastoma, 9 being <1 year of age. CONCLUSIONS: A decrease in the proportion of early deaths associated with childhood cancer has occurred during the past 2 decades. This decrease may reflect earlier diagnosis or improved imaging capabilities, surgical techniques, medical therapy, and supportive care. Awareness among pediatricians, general practitioners, and emergency physicians is warranted, with a focus on high-risk groups for early detection among childhood cancer patients.

Adolescent↗

Steroid-triggered death by autophagy.

Programmed cell death is a critical part of normal development, removing obsolete tissues or cells and sculpting body parts to assume their appropriate form and function. Most programmed cell death occurs by apoptosis of individual cells or autophagy of groups of cells. Although these pathways have distinct morphological characteristics, they also have a number of features in common, suggesting some overlap in their regulation. A recent paper by Lee and Baehrecke provides further support for this proposal.(1) These authors present, for the first time, a genetic analysis of autophagy, using the steroid-triggered metamorphosis of Drosophila as a model system. They demonstrate a remarkable degree of overlap between the control of apoptosis and autophagy as well as a key role for the steroid-inducible gene E93 in directing the autophagic death response. This paper also shows that E93 can direct cell death independently from the known death-inducer genes, defining a novel death pathway in Drosophila.

Animals↗

Sudden cardiovascular death following myocardial infarction: the importance of left ventricular systolic dysfunction and congestive heart failure.

BACKGROUND: To study the prognostic information of congestive heart failure (CHF) and left ventricular systolic dysfunction regarding sudden and non-sudden cardiovascular death (SCD and non-SCD) in patients with acute myocardial infarction (MI), as this may indicate the potential benefit of implantable defibrillators. METHODS: Data from consecutive patients with acute MI screened in 1990-92 for the TRAndolapril Cardiac Evaluation (TRACE) study were entered into a registry. A total of 5502 patients were alive 30 days after the MI and were followed for up to 4 years with respect to cause of death. SCD was defined as cardiovascular death within 1 h of onset of symptoms. An echocardiography was performed 1-6 days after the admission and evaluated centrally using the wall motion index (WMI). RESULTS: Half of the patients had CHF and 17% of the patients had WMI < or =1.0 (corresponding to an ejection fraction < or =0.30). During follow-up 431 patients died from SCD and 606 from non-SCD. The risk ratios for SCD and non-SCD associated with WMI < or =1.0 were 3.17 and 2.95, transient CHF 2.01 and 1.46, and permanent CHF 3.71 and 4.42, respectively. No risk factor was a specific marker of SCD or non-SCD. The 3-year probability of SCD was 7.9% for patients with transient CHF, 13.3% for permanent CHF, and 15.5% for WMI < or =1.0. CONCLUSIONS: CHF and low WMI identify a relevant proportion of patients with MI who are at high absolute risk of SCD. This study indicates the relevance of defibrillators in consecutive post-MI patients with left ventricular dysfunction or clinical signs of heart failure.

Aged↗

An alternatively spliced C. elegans ced-4 RNA encodes a novel cell death inhibitor.

The C. elegans gene ced-4 is essential for programmed cell death. We report that ced-4 encodes two transcripts and that whereas the major transcript can cause programmed cell death, the minor transcript can act oppositely and prevent programmed cell death, thus defining a novel class of cell death inhibitors. That ced-4 has both cell-killing and cell-protective functions is consistent with previous genetic studies. Our results suggest that the dual protective and killer functions of the C. elegans bcl-2-like gene ced-9 are mediated by inhibition of the killer and protective ced-4 functions, respectively. We propose that a balance between opposing ced-4 functions influences the decision of a cell to live or to die by programmed cell death and that both ced-9 and ced-4 protective functions are required to prevent programmed cell death.

Alleles↗