Determination of Brain Death

With the careful application of the principles outlined herein, brain death can be determined with certainty. There have been no documented reports of survivors when these guidelines have been followed. The traid of a known mechanism of brain injury, absence of contributing metabolic or toxic central nervous system depression and absence of demonstrable brain function is sufficient to determine brain death clinically and, in most states, legally. The use of apneic oxygenation protects cadaver organs for transplantation during the period needed to prove that a patient cannot breathe.Very little can ameliorate the tragedy of sudden and unexpected fatal cerebral injury. Nonetheless, the concept of brain death is well established, and there is no longer a medical or an ethical reason to prolong unnecessary support of these patients.     

Testing Thermal Death Data for Significant Nonlogarithmic Behavior

The thermal death behavior of Bacillus stearothermophilus spores in distilled water suspensions is nonlogarithmic in dynamic as well as static tests. The explanation of heat lags as the cause of nonlogarithmic behavior is incorrect.     

“脑死亡”引发的伦理学思考

脑死亡是本校高中2年级生命伦理学选修课的一节。此节涉及人们比较敏感的话题——死亡。介绍了脑死亡这一科学的定义和传统的死亡定义以及判定方式．讨论了由于对死亡的认识差异带来的伦理学问题。选取脑和神经系统的生物学基础知识和很多脑死亡案例作为学习内容和讨论对象,以师生互动和积极讨论为主要形式,学生积极参与思考和讨论,对脑死亡及其引发的伦理问题有了更科学和深入的认识。     

Reviving Brain Death: A Functionalist View

Recently both whole brain death (WBD) and higher brain death (HBD) have come under attack. These attacks, we argue, are successful, leaving supporters of both views without a firm foundation. This state of affairs has been described as “the death of brain death.” Returning to a cardiopulmonary definition presents problems we also find unacceptable. Instead, we attempt to revive brain death by offering a novel and more coherent standard of death based on the permanent cessation of mental processing. This approach works, we claim, by being functionalist instead of being based in biology, consciousness, or personhood. We begin by explaining why an objective biological determination of death fails. We continue by similarly rejecting current arguments offered in support of HBD, which rely on consciousness and/or personhood. In the final section, we explain and defend our functionalist view of death. Our definition centers on mental processing, both conscious and preconscious or unconscious. This view provides the philosophical basis of a functional definition that most accurately reflects the original spirit of brain death when first proposed in the Harvard criteria of 1968.     

Legal Standards for Brain Death and Undue Influence in Euthanasia Laws

A major appellate court decision from the United States seriously questions the legal sufficiency of prevailing medical criteria for the determination of death by neurological criteria. There may be a mismatch between legal and medical standards for brain death, requiring the amendment of either or both. In South Australia, a Bill seeks to establish a legal right for a defined category of persons suffering unbearably to request voluntary euthanasia. However, an essential criterion of a voluntary decision is that it is not tainted by undue influence, and this Bill falls short of providing adequate guidance to assess for undue influence.     

Modelling the Brain for Rotational Loading: Shear Effects and Other Complications

Abstract

This study considers modelling the brain due to rotation of the skull where, at lower frequencies, the shear property of the material is important. Investigations reported here cover the effect of elastic and viscoelastic (lossy) cerebral material, the effect of the Falx protruding into the brain, the gap around the Falx and the brain filled with non viscous fluid in addition to different models of the Falx with bending or membrane stiffness. Analytical benchmark formulations are also described for the simple 2D plane strain in a cylinder produced by a half-sine rotation on the outer periphery which allows numerical (Finite Element) models to be validated. The results show the importance of the material properties, duration of loading and amplitude of loading as well as the influence of the partition. The results are shown for predicted maximum Principal strains in the models, as this may well be indicative of whether damage of the brain tissue occurs.     

Modelling the Brain for Rotational Loading: Shear Effects and Other Complications

This study considers modelling the brain due to rotation of the skull where, at lower frequencies, the shear property of the material is important. Investigations reported here cover the effect of elastic and viscoelastic (lossy) cerebral material, the effect of the Falx protruding into the brain, the gap around the Falx and the brain filled with non viscous fluid in addition to different models of the Falx with bending or membrane stiffness. Analytical benchmark formulations are also described for the simple 2D plane strain in a cylinder produced by a half-sine rotation on the outer periphery which allows numerical (Finite Element) models to be validated. The results show the importance of the material properties, duration of loading and amplitude of loading as well as the influence of the partition. The results are shown for predicted maximum Principal strains in the models, as this may well be indicative of whether damage of the brain tissue occurs.     

Hypoxia Ischemia-Mediated Cell Death in Neonatal Rat Brain

The examination of Bcl-2-associated X protein (Bax) protein’s role in the activation of cognate nuclear, mitochondrial and ER cell death signaling cascades and the resulting effects on cell death phenotype in the brain after neonatal hypoxia-ischemia (HI) requires an understanding of neonatal HI insult and progression, as well as, its dysfunctional outcomes. In addition, knowledge of key concepts of oxidative stress, a major injurious component of HI, and the different cell death phenotypes (i.e. apoptosis and necrosis) will aid the design of appropriate useful experimental paradigms. Here we discuss organelle cell death signaling cascades in the context of the different cell death phenotypes associated with animal models of neonatal hypoxia ischemia and tissue culture models used in the study of hypoxia ischemia, focusing on the intracellular shifts of the Bcl-2 associated X protein (Bax) in the hypoxic brain. Special issue article in honor of Dr. Anna Maria Giuffrida-Stella.     

The Case for Reasonable Accommodation of Conscientious Objections to Declarations of Brain Death

Since its inception in 1968, the concept of whole-brain death has been contentious, and four decades on, controversy concerning the validity and coherence of whole-brain death continues unabated. Although whole-brain death is legally recognized and medically entrenched in the United States and elsewhere, there is reasonable disagreement among physicians, philosophers, and the public concerning whether brain death is really equivalent to death as it has been traditionally understood. A handful of states have acknowledged this plurality of viewpoints and enacted “conscience clauses” that require “reasonable accommodation” of religious and moral objections to the determination of death by neurological criteria. This paper argues for the universal adoption of “reasonable accommodation” policies using the New Jersey statute as a model, in light of both the ongoing controversy and the recent case of Jahi McMath, a child whose family raised religious objections to a declaration of brain death. Public policies that accommodate reasonable, divergent viewpoints concerning death provide a practical and compassionate way to resolve those conflicts that are the most urgent, painful, and difficult to reconcile.     

Mitochondrial Glutathione: A Modulator of Brain Cell Death

The small fraction of glutathione in mitochondria in nonneural tissues is an important contributor to cell survival under some conditions. However, there has been only limited characterization of the properties and function of mitochondrial glutathione in cells from the brain. In astrocytes in culture, highly selective depletion of this glutathione pool does not affect cell viability, at least in the first 24 h, but does greatly increase susceptibility to exposure to nitric oxide or peroxynitrite. In vivo, a selective partial loss of glutathione develops during focal cerebral ischemia and persists during reperfusion. The timing and distribution of glutathione loss shows an apparent association with the likelihood that tissue infarction will subsequently develop. Furthermore, infarct volume is greatly decreased by intracerebroventricular infusion of glutathione monoethylester, a compound that can increase mitochondrial glutathione. Together these recent findings indicate that alterations in mitochondrial glutathione are likely to contribute to the severity of tissue damage in stroke and possibly other neurological disorders. Thus, this antioxidant pool provides a potentially useful target for therapeutic intervention.     

Impact of the Brain Death Ruling in Washington State

In a 1980 Washington State Supreme Court decision, brain death was recognized as a means of determining death, but the court declined to specify a procedural mechanism to be followed. According to a survey of hospitals in Washington, the decision has had little impact in the state, apparently due to the medical profession''s unfamiliarity with it. As a result of the survey, we have identified problems of procedure and interaction with the legal system. A consensus of those contacted was that no formal, hospital-mandated definition of brain death is needed.     

猪心脏移植中供体急性脑死亡模型的初步研究

目的建立猪心脏移植供体的急性脑死亡模型,观察急性脑死亡前及后1、5、10 min时的血流动力学和血浆中儿茶酚胺释放的变化并进行初步探讨。方法采用30~40 kg的猪8只,急性脑死亡前为对照组,急性脑死亡后为实验组。测定脑死亡前基础水平及脑死亡后1、5、10 min时血流动力学改变和血浆中儿茶酚胺释放的变化,并对二者的变化进行初步探讨。结果急性脑死亡后1 min时血流动力学及儿茶酚胺水平改变最明显,心率增加了88%,收缩压升高了132%,心排量增加了80%,肾上腺素(E)和去甲肾上腺素(NE)分别升高240%和241%,多巴胺(DA)没有明显增加。随后二者均持续下降,至10 min时已降至基础水平以下。血流动力学改变的程度及时间分布与儿茶酚胺中的肾上腺素和去甲肾上腺素一致。结论急性脑死亡可造成机体血流动力学及血浆儿茶酚胺水平的剧烈改变,血中儿茶酚胺含量升高是造成急性脑死亡后血流动力学改变的原因,其中E和NE与血流动力学改变直接相关。     

Death and brain death: a new formulation for Canadian medicine. Canadian Congress Committee on Brain Death.

Between June 1984 and December 1986, 35 patients with acute myocardial infarction received streptokinase intravenously within 3 hours after the beginning of chest pain and underwent percutaneous transluminal coronary angioplasty (PTCA) either immediately (in 2 cases) or 1 to 19 (mean 4.4) days later (in 33). The rate of successful PTCA was 89%. Reocclusion occurred in one patient. The mean percentage of stenosis decreased from 86% to 11%. The mean trans-stenotic gradient was reduced from 41 to 11 mm Hg. The results suggest that in patients whose condition is stable, PTCA performed a few days after thrombolysis is a valuable alternative to more aggressive treatment with immediate PTCA.     

Differentiation and Death of Premyelinating Oligodendrocytes in Developing Rodent Brain

Previous studies have indicated that newly formed oligodendrocytes are dynamic cells whose production, survival, and differentiation depend upon axonal influences. This study has characterized the appearance and fate of newly formed oligodendrocytes in developing rat brain. Oligodendrocytes appear in predictable locations and radially extend DM-20–positive processes that cover 80-μm domains in the cortex and 40-μm domains in the corpus callosum. These premyelinating oligodendrocytes have one of two fates: they myelinate axons or degenerate. Between 7 and 21 d after birth, ~20% of premyelinating oligodendrocytes identified in the cerebral cortex were degenerating. Oligodendrocytes that ensheathed axons expressed and selectively targeted proteolipid protein to compact myelin and did not degenerate. These observations support the hypothesis that axonal influences affect oligodendrocyte survival, differentiation, and expression of proteolipid protein gene products.     

Determination of Brain Interstitial Concentrations by Microdialysis

Microdialysis is an extensively used technique for the study of solutes in brain interstitial space. The method is based on collection of substances by diffusion across a dialysis membrane positioned in the brain. The outflow concentration reflects the interstitial concentration of the substance of interest, but the relationship between these two entities is at present unclear. So far, most evaluations have been based solely on calibrations in saline. This procedure is misleading, because the ease by which molecules in saline diffuse into the probe is different from that of tissue. We describe here a mathematical analysis of mass transport into the dialysis probe in tissue based on diffusion equations in complex media. The main finding is that diffusion characteristics of a given substance have to be included in the formula. These include the tortuosity factor (lambda) and the extracellular volume fraction (alpha). We have substantiated this by studies in a well-defined complex medium (red blood cell suspensions) as well as in brain. We conclude that the traditional calculation procedure results in interstitial concentrations that are too low by a factor of lambda 2/alpha for a given compound.