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The brain death is defined as the complete and irreversible absence of the cerebral and brain stem functions. In case of the dissociated lack of these functions an EEG activity can still be recognizable even in the presence of a brain death syndrome. Own observations in 57 persons with brain death are discussed.
In a matched case-control study of an occupational cohort in East Tennessee, data from the death certificates of 608 cases and controls were abstracted and analyzed in order to investigate possible risk factors associated with the certification on the death certificate of an ill-defined cause of death. There was a very strong association between the ill-defined classification and the certifier, especially if the certifier was a medical examiner (OR = 10.4, 95% CI: 6.0, 18.0).
Although used extensively, there is little published information on the prognostic ability of exercise 201Tl scintigraphy. Accordingly, 1 yr after testing we contacted 819 patients without previous MI or CABG seen in our laboratory during a 2-yr period. Events were defined as death from a cardiovascular cause, nonfatal MI, or worsening clinical state requiring CABG. The event rate was 3.9 events per 100 patients per year. There was univariate prognostic information when comparing the highest and lowest categories as risk ratios for chest pain characteristics (2.7), sex (2.3), exercise duration (3.1), ST slope (2.5), and thallium pattern (11.6), intensity of perfusion defect (17.2), and number of abnormal regions (8.7). However, the strongest predictors were also the least common. Prognostic ability was improved by combining the results categorically, as the number of abnormal tests (13.9). The highest risk ratio, 20.5:1, was obtained by combining results through discriminant function analysis. We conclude that exercise thallium scintigraphy provides prognostic information, although the most predictive patterns are uncommon. Combining the results of multiple test results improves the prognostic ability.
The prognosis of cerebral venous sinus thrombosis (CVST) is variable, and outcome may range from complete recovery to death. Prognostic factors to predict outcome in the acute phase of CVST have not been analysed in a prospective study. Prognostic factors in patients enrolled in a clinical treatment trial were prospectively investigated. Poor outcome after 12 weeks, defined as death or dependency (Oxford handicap score > or =3), was used as the principle outcome measure. Univariate relations between possible prognostic factors and outcome at 12 weeks were analyzed with chi(2) tests. Treatment and all factors associated with prognosis (p< or = 0.25) were forced into a logistic regression model with a forward selection procedure. Fifty nine patients (50 women, nine men) were studied, with a mean age of 37 years (range 18 to 80 years). After 12 weeks 10 patients (17%) had a poor outcome. The univariate identified factors related to poor outcome were papilloedema, altered consciousness, coma, age older than 33 years, diagnostic delay < or =10 days, intracerebral haemorrhage, and involvement of the straight sinus. Isolated intracranial hypertension and a delta sign on CT were associated with good outcome. In the multivariate analysis coma and cerebral haemorrhage were significantly associated with a poor outcome, with odds ratios of 8.2 (95% confidence interval (95% CI) 1. 3-50.1) and 20.7 (95% CI 1.6-264.3) respectively. Involvement of the straight sinus was also weakly, but not significantly, associated with poor outcome. In conclusion, coma and intracerebral haemorrhage are independent predictors for poor outcome of CVST.
An accurate prediction of the prognosis of patients with idiopathic membranous nephropathy (iMN) should allow restriction of immunosuppressive treatment to patients who are at highest risk for ESRD. On the basis of retrospective studies, it has previously been suggested that the urinary excretions of beta2-microglobulin (Ubeta2m) and IgG (UIgG) are useful predictors of renal insufficiency in patients with iMN. The threshold values of 0.5 micro/min (Ubeta2m) and 250 mg/24 h (UIgG) have been validated in a new and larger patient cohort. From 1995 onward, 57 patients with iMN (38 men, 19 women; age 48 +/- 16 yr), a nephrotic syndrome, and a serum creatinine level </=1.5 mg/dl were studied prospectively. At baseline, a standardized measurement was carried out to determine renal function and protein excretion. The end point renal death was defined as a serum creatinine exceeding 1.5 mg/dl or a rise of serum creatinine of >50%. Mean (+/-SD) follow-up was 53 +/- 23 mo. Thus far, 25 (44%) of the patients have reached the end point renal death. Multivariate analysis confirmed Ubeta2m as the strongest independent predictor for the development of renal insufficiency. Sensitivity and specificity were 88 and 91%, respectively, for Ubeta2m, and both were 88% for UIgG. When the excretions of both proteins were combined, specificity improved to 97%. It is concluded that the present data validate the accuracy of Ubeta2m and of UIgG in predicting renal outcome in patients with iMN. These markers can be used to guide decisions on the start of immunosuppressive treatment.
Hypothermia is defined as a subnormal body temperature. In this article, hypothermia refers to the loss of core temperature from exposure. When death results from hypothermia, a series of gastric mucosal erosions known as "Wischnewski ulcers" (1) frequently occur. In examining case material of the Onondaga County Medical Examiner's Office, a characteristic pattern of these ulcerations was seen that was indicative of severe physiologic stress and/or hypothermia. While not pathognomonic of hypothermia, the incidence of the erosions in a specific pattern has been closely associated with deaths in which hypothermia played a significant role. In hypothermia, the erosions, usually shallow and approximately 0.1-0.5 cm in diameter, are set in lines with roughly equidistant spacing, thereby forming a pattern of rectangles with the corners marked by the ulcerations.
Solamargine possessed a potent cytotoxicity to human hepatocyte (Hep3B) and normal skin fibroblast. The inhibition curves of solamargine to the both cells were essentially overlapped, suggesting a parallel effect for the cell death. To define mechanism of cytotoxicity of solamargine, the changes of morphology and DNA content in cells were studied. A sub-G1 cell stage was drastically increased after 3-h incubation with solamargine. The results evidence that solamargine arises cell death by apoptosis. In addition, the gene expression of TNFR I were up-regulated within 30 min of solamargine treatment. Since TNF Receptor I has been involved in apoptosis, the overexpression of TNF receptor I may be related with the mechanism of cytotoxicity of solamargine. This communication is the first report that a component of Chinese herbs triggers gene expression of human TNFR I which may lead to cell apoptosis.
The concept of person is integral to bioethical discourse because persons are the proper subject of the moral domain. Nevertheless, the concept of person has played no role in the prevailing formulation of human death because of a purported lack of consensus concerning the essential attributes of a person. Beginning with John Locke's fundamental proposition that person is a 'forensic term', I argue that in Western society we do have a consensus on at least one necessary condition for personhood, and that is the capacity for conscious experience. When we consider the whole brain formulation of death, and the most prominent defense of it by the President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research, we can readily identify the flaws that grow out of the failure to define human death as the permanent loss of the capacity for conscious experience. Most fundamental among these flaws is a definition of human death that reduces persons to the capacity of the brain to regulate purely physiological functioning. Such a formulation would, in theory, apply to any member of the animal kingdom. I suggest that an appropriate concept of death should capture what it is about a particular living being that is so essential to it that the permanent loss of that thing constitutes death. What is essential to being a human being is living the life of a person, which derives from the capacity for conscious experience.
Heart failure (HF) is characterized by neurohormonal activation of the sympathetic nervous and renin-angiotensin systems. Genetic polymorphisms in these systems could alter the prognosis in HF. We hypothesized the genetic polymorphisms in the sympathetic nervous and renin-angiotensin systems are associated with adverse outcomes, defined as death or heart transplantation in patients with HF. A total of 227 patients with HF were enrolled from a tertiary care clinic and followed for outcomes for < or =4 years. Eight polymorphisms in 6 genes were genotyped: beta(1)-adrenergic receptor (ADRB1, S49G, R389G), beta(2)-adrenergic receptor (ADRB2, G16R, Q27E), alpha(2c)-adrenergic receptor (ADRA2C, insertion/deletion 322-325), angiotensinogen (AGT, M235T), angiotensin receptor type 1 (AGTR1, 1166A>C), and angiotensin-converting enzyme (ACE, insertion/deletion in intron 16). Most patients were treated according to consensus guidelines. Male gender (hazard ratio 2.24, 95% confidence interval 1.27 to 3.94), higher New York Heart Association functional class (hazard ratio 2.54, 95% confidence interval 1.84 to 3.52), and 2 copies of ADRB2 Arg16Gln27 haplotype (hazard ratio 1.91, 95% confidence interval 1.09 to 3.36) increased the risk of adverse outcomes. In contrast, a higher serum sodium level (hazard ratio 0.91, 95% confidence interval 0.86 to 0.97) and higher creatinine clearance (hazard ratio 0.99, 95% confidence interval 0.98 to 0.99) decreased the risk of adverse outcomes. None of the other genotypes/haplotypes were associated with adverse outcomes. In conclusion, ADRB2 Arg16Gln27 haplotype may significantly increase the risk of adverse outcomes in patients with HF receiving contemporary HF pharmacotherapy.
The temporal distribution and mechanism of death were studied in a large multicenter secondary prevention trial (Aspirin Myocardial Infarction Study) in which acute witnessed death represented 72% (270 of 376) of the deaths due to arteriosclerotic heart disease. Instantaneous deaths represented 28.9% (78 of 270) of the acute witnessed deaths; 45.2% (122 of 270) occurred in the first hour after the onset of symptoms and were defined as sudden deaths. In the subsequent 23 hours, an additional 113 deaths (41.8%) occurred and were defined as intermediate deaths; 29 late deaths (10.7%) occurred after 24 hours. Cardiac arrhythmia was the mechanism of death in 83% (194 of 235) of deaths within 24 hours. Univariate analysis of baseline clinical and electrocardiographic characteristics indicates that a history of congestive heart failure, cardiomegaly, angina pectoris, multiple myocardial infarctions and therapy with digitalis and nitroglycerin were more common in those who died than in survivors, regardless of the timing of death.
OBJECTIVE: The aim of our study was to establish the etiology of and risk factors for infective endocarditis (IE) and determine the prognostic factors for adverse outcome during hospital admission in a Turkish population. MATERIAL AND METHODS: Between January 2002 and January 2004, the clinical and laboratory features of 112 consecutive adult patients (>18 years) with diagnosis of IE who were referred to the infectious diseases clinics/departments of 17 teaching hospitals in Turkey were evaluated. Cases of IE were defined according to the modified Duke Criteria. Mortality was defined as death occurring within 30 days or during hospital stay period. Univariate and multivariate analyses were performed to predict the factors related to fatal outcome. RESULTS: A total of 112 consecutive patients presented with 101 definite and 11 probable IE episodes were defined according to the modified Duke Criteria. The mean age was 45.2+/-19.9. Fifty percent of the patients were male. Ninety (60.4%) of the 112 patients had risk factors for IE and 48 (42.9%) of them had >or=2 risk factors. On the other hand, 49.1% of patients had cardiac risk factors. Blood cultures were positive in 94 (83.9%) cases. Staphylococci were the most common agents (50.0%), followed by streptococci (28.7%) and enterococci (16.0%). Native cardiac valves were detected in 93 (83%) of the episodes of suspected IE. Valvular involvement was present in 103 (92%) patients; the mitral valve, alone or in combination with other valves, was affected in 70 (62.5%) of the patients. Echocardiography detected vegetations in 105 patients (93.8%). The mortality rate was 28.6%. Three factors were independently associated with mortality: haemodialysis OR: 14.5 (95% CI: 1.5-138.2), mobile vegetation OR: 4.8 (95% CI: 1.5-15.4) and mental alteration OR: 4.1 (95% CI: 1.1-15.6). CONCLUSION: Mortality is still high in IE. Our data indicate that patients with altered mental status, mobile vegetation, or on haemodialysis had poorer prognosis.
Although 2DE is considered the most sensitive method for detecting vegetations in infective endocarditis, the independent clinical significance of these vegetations continues to be debated. To further examine this, we identified 74 patients who were diagnosed as having infective endocarditis over a 54-month period. The 50 patients who underwent 2DE examination form the basis of this report. Definite vegetations were present in 21 (42%) patients and measured 1.2 +/- 0.2 cm2. The vegetation was localized to the aortic valve in 10 patients, the mitral valve in eight, and the tricuspid valve in three. A major complication, defined as death, new-onset congestive heart failure, major arterial embolus, or valve surgery occurred in 86% of the vegetative endocarditis patients compared to 62% of those without vegetations. Among those patients with vegetations, death occurred in 24%, heart failure in 38%, arterial embolus in 48%, and surgery in 43%. This compared to 7%, 21%, 21%, and 24%, respectively, in those patients without vegetations. These data support the concept that 2DE detection of a vegetation defines a high-risk subgroup of patients with infective endocarditis in whom careful monitoring and aggressive management are warranted.
Circulatory collapse and sudden death was defined retrospectively as one of the major critical problems among 23 respirator-dependent patients with amyotrophic lateral sclerosis (ALS). Six cases died from sudden cardiac arrest or anoxic encephalopathy following the circulatory collapse. In five among the six cases, sudden death or cardiac arrest occurred during sleep at night. Eight cases had had episodes of marked fluctuation of blood pressure before death, including paroxysmal elevation of blood pressure and heart rate, and successive sudden pressure fall without compensatory tachycardia. The spells of hypotension often occurred during sleep. In addition, the prospective study of diurnal variation of blood pressure, heart rate, plasma norepinephrine and plasma renin activity in nine respirator-dependent ALS patients showed continuous tachycardia and more remarkable nocturnal decrease of blood pressure compared with the control subjects. Plasma norepinephrine levels were constantly higher in the ALS patients particularly in a daytime. These indicate the continuous sympathetic hyperactivity in ALS. We discuss the cause of the circulatory collapse and sudden death in the respirator-dependent ALS patients in terms of the autonomic dysregulatory mechanism or the sympathetic hyperactivity.
Kawasaki disease (KD) primarily affects infants and is rarely fatal in young adults. The sequelae of KD can result in death months to years after the exposure to the causative agent. Such deaths are defined as Stage IV KD, which is characterized by the formation of multiple aneurysms in the coronary arteries, calcification and recanalization of the obstructed portions of the coronary arteries, and myocardial infarction and ischemia. A 10-year retrospective review of sudden deaths in Allegheny County, Pennsylvania, identified two fatal cases of Stage IV KD involving young adults. These two young adults were healthy and completely asymptomatic; they had no identifiable risk factors for cardiovascular disease before the fatal event. One adult was involved in vigorous exercise, and the other was recumbent in bed at the time of death.
This paper undertakes an analysis of the scientific criteria used in the diagnosis of death and underscores the importance of intellectual rigor in the definition of medical concepts, particularly regarding such a critical issue as the diagnosis of death. Under the cardiorespiratory criterion, death is defined as "the irreversible cessation of the functioning of an organism as a whole", and the tests used to confirm this criterion (negative life-signs) are sensitive and specific. In this case, cadaverous phenomena appear immediately following the diagnosis of death. On the other hand, doubts have arisen concerning the theoretical and the inner consistency of the criterion of brain death, since it does not satisfy the definition of "the irreversible cessation of the functioning of an organism as a whole", nor the requirement of "total and irreversible cessation of all functions of the entire brain, including the brain stem". There is evidence to the effect that the tests used to confirm this criterion are not specific enough. It is clear that brain death marks the beginning of a process that eventually ends in death, though death does not occur at that moment. From an ethical point of view, the conflict arises between the need to provide an unequivocal diagnosis of death and the possibility of saving a life through organ transplantation. The sensitive issue of brain death calls for a more thorough and in-depth discussion among physicians and the community at large.
OBJECTIVE: To assess the characteristics and short-term outcome of patients, undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES), in routine clinical practice. DESIGN: Observational study. PLACE AND DURATION OF STUDY: The Aga Khan University Hospital, from 2002 to 2003. PATIENTS AND METHODS: All the patients who underwent PCI with DES at cath lab, AKUH, during the year 2002 and 2003 were included. Data was collected from database and by reviewing clinical records. Follow-up data for a period of 6-9 months was collected from the clinical records and by a telephone interview where required. RESULTS: A total of 141 patients underwent PCI with DES at AKUH during the year 2002 and 2003. This study was predominantly male dominated (approximately 77%), with a mean age of 55+/-11 years. Thirty-nine percent were diabetics, and 53% were hypertensives. Twelve percent of patients had prior coronary artery bypass graft surgery (CABG) and 17% had prior PCI. Two or more than two lesions were attempted in 55% of patients. Majority (84.4%) of lesions were moderate to high risk category. Six to nine months follow-up was available in 133 (94%) patients. The only death was due to heart failure in the presence of a patent stent. Nearly 8% had clinical angina and 3.8% had myocardial infarction (MI) during follow-up. Target lesion revascularization (TLR) was performed in 4.6%. Major adverse cardiac events (MACE), defined as death, MI, and TLR occurred in 6.8% of patients. CONCLUSION: This data shows that DES are being used in a broad variety of clinical settings in routine or real life clinical practice. The outcome is excellent and comparable to randomized trials.
OBJECTIVE: To determine and analyse peri-operative mortality with particular emphasis on avoidable factors, in the hope that this information will lead to an improvement in standards. DESIGN: Review of all anaesthetic-associated deaths (AADs) during the year 1992. All available records were scrutinised and further information was obtained from mortality meetings and confidential discussions. SETTING: Harare Central and Parirenyatwa hospitals, which are referral centres. PATIENTS: Out of 34,553 subjects presenting for surgical procedures, there were 89 deaths between 1 January and 31 December 1992. MAIN OUTCOME MEASURES: Incidence of AAD, avoidable mortality rate (AMR) and classification of avoidable surgical, anaesthetic and administrative factors. MAIN RESULTS: The incidence of AAD per 1,000 anaesthetics was 2.58. (AAD was defined as death within 24 hours of anaesthesia or failure of a patient, who was previously conscious, to regain consciousness.) There were avoidable factors in 45 (51%) of the deaths. The overall AMR was 1.34 per 1,000 operations (death classified as avoidable if mismanagement contributed to mortality). The AMR (surgical), AMR (anaesthetic) and AMR (administrative) were 0.80, 0.33 and 0.21 respectively. Scoring in each category of avoidability was done proportionately, with a maximum of one point per death awarded where there were avoidable factors). The commonest avoidable factors (in order of frequency) were uncontrolled haemorrhage, poor postoperative management, poor pre-operative management and anastomotic dehiscence. CONCLUSIONS: This audit reveals that there were avoidable factors in 51% of peri-operative deaths. It should be possible to reduce the mortality rate by developing preventive measures.
Chinese hamster ovary (CHO) cells were pulsed by using brief intense square-wave electric field pulses. The electrical treatment induced a transient local permeabilization of the cell membrane. The growth of CHO cells after electropulsation in an iso-osmotic pulsing buffer with low ionic content was measured. Parallel experiments evaluated cell death which took place in the minute range after electropulsation (short-term death) and the cell death upon 24 h (long-term death). Short-term cell death was defined as the case of cells with membrane still permeable to Direct-blue at 15 min after electropulsation. It was observed only under stringent pulsing conditions where electropermeabilization of the two sides of the cell was triggered. The long-term cell death, i.e., the inability of some pulsed cells to grow was observed as soon as permeabilization had been triggered. The higher the permeabilization level of the cell population was, the higher the long-term cell death level was. The cell death was linearly related to the reciprocal of the electric field intensity, i.e., to the fraction of the membrane area electrically brought to the permeable state. From this work, it appeared that for high levels of permeabilization of a cell suspension, best cell survivals were obtained if limited alterations were triggered over a large area of the plasma membrane (single pulse with high intensity) than if a small area of the membrane was strongly altered (repetitive pulses with small intensity). The highest yield of viable permeabilized cells was achieved when using one single pulse of duration up to 1 ms.