PHILOSOPHICAL CONSIDERATIONS ON BRAIN DEATH AND THE CONCEPT OF THE ORGANISM AS A WHOLE

Since intensive care medicine enables us to maintain blood circulation and respiration artificially for some time, the usual criteria for death, such as cardiac arrest and cessation of respiration, are not applicable in all cases. Thus, the irreversible breakdown of the brain functions have come to be accepted as the most prominent factor for the occurrence of death. This criterion is linked primarily to the disintegration of the organism as a whole. Yet the controversy surrounding the moment when a man can be declared dead has not yet been resolved. The decisive weak point in this controversial discussion seems to be that the notion of the "organism as a whole" is inadequately defined. The aim of this work is to fill this void. We developed four general criteria of life: integration, coordination, dynamics, and immanency. Moreover, four additional characteristics are necessary for a living being (organism as a whole): completion, indivisibility, autofinality, and identity. If one of these four characteristics is missing we can only speak of derivative life but not of a living being. In a brain dead body one finds a number of signs of life. These signs of life, however, are not signs of an organism as a whole but signs of a physiological combination of organs whose parts — directed from the outside - are dependent on each other. The brain dead body lacks the four criteria of a living being. Thus it is no longer a living person but purely derivated biological life

PHILOSOPHICAL CONSIDERATIONS ON BRAIN DEATH AND THE CONCEPT OF THE ORGANISM AS A WHOLE

Since intensive care medicine enables us to maintain blood circulation and respiration artificially for some time, the usual criteria for death, such as cardiac arrest and cessation of respiration, are not applicable in all cases. Thus, the irreversible breakdown of the brain functions have come to be accepted as the most prominent factor for the occurrence of death. This criterion is linked primarily to the disintegration of the organism as a whole. Yet the controversy surrounding the moment when a man can be declared dead has not yet been resolved. The decisive weak point in this controversial discussion seems to be that the notion of the "organism as a whole" is inadequately defined. The aim of this work is to fill this void. We developed four general criteria of life: integration, coordination, dynamics, and immanency. Moreover, four additional characteristics are necessary for a living being (organism as a whole): completion, indivisibility, autofinality, and identity. If one of these four characteristics is missing we can only speak of derivative life but not of a living being. In a brain dead body one finds a number of signs of life. These signs of life, however, are not signs of an organism as a whole but signs of a physiological combination of organs whose parts — directed from the outside - are dependent on each other. The brain dead body lacks the four criteria of a living being. Thus it is no longer a living person but purely derivated biological life

IS THERE A CORTICAL BLOOD FLOW REDISTRIBUTION PATTERN RELATED WITH PERSEVERATIVE ERROR IN SCHIZOPHRENIA?

Background: We studied relative cortical blood flow (relCBF) patterns associated to correct performance (CP) and perseverative error (PE) during Wisconsin Card Sorting Test (WCST) execution, in controls and patients with schizophrenia. Subjects and methods: relCBF (regional cortical blood flow (rCBF) / whole cortex blood flow) of 10 well defined cortical regions was measured in 18 patients with schizophrenia and 13 healthy controls by a Technetium – 99 – HMPAO – SPECT, at rest and while they performed WCST. Results: Patients made significantly more PE than controls during WCST performance. In patients, we found a significant correlation between PE and relCBF in right occipital cortex. In controls, we found a significant correlation between CP and relCBF of several cortical regions during WCST execution: left orbitofrontal cortex and left global frontal cortex positively and parietal bilateral cortex negatively. PE was inversely correlated with relCBF in left temporal cortex. Conclusions: Successful WCST performance is associated to a high left frontal activity in controls but not in patients. The severity of PE during WCST performance is associated to a low left frontal-temporal activity in controls and to a high right parietal-occipital activity in schizophrenia. This may represent a cortical activity redistribution pattern related to perseveration in schizophrenia

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation