220 research outputs found
Brain death, states of impaired consciousness, and physician-assisted death for end-of-life organ donation and transplantation
In 1968, the Harvard criteria equated irreversible coma and apnea (i.e., brain death) with human death and later, the Uniform Determination of Death Act was enacted permitting organ procurement from heart-beating donors. Since then, clinical studies have defined a spectrum of states of impaired consciousness in human beings: coma, akinetic mutism (locked-in syndrome), minimally conscious state, vegetative state and brain death. In this article, we argue against the validity of the Harvard criteria for equating brain death with human death. (1) Brain death does not disrupt somatic integrative unity and coordinated biological functioning of a living organism. (2) Neurological criteria of human death fail to determine the precise moment of an organism’s death when death is established by circulatory criterion in other states of impaired consciousness for organ procurement with non-heart-beating donation protocols. The criterion of circulatory arrest 75 s to 5 min is too short for irreversible cessation of whole brain functions and respiration controlled by the brain stem. (3) Brain-based criteria for determining death with a beating heart exclude relevant anthropologic, psychosocial, cultural, and religious aspects of death and dying in society. (4) Clinical guidelines for determining brain death are not consistently validated by the presence of irreversible brain stem ischemic injury or necrosis on autopsy; therefore, they do not completely exclude reversible loss of integrated neurological functions in donors. The questionable reliability and varying compliance with these guidelines among institutions amplify the risk of determining reversible states of impaired consciousness as irreversible brain death. (5) The scientific uncertainty of defining and determining states of impaired consciousness including brain death have been neither disclosed to the general public nor broadly debated by the medical community or by legal and religious scholars. Heart-beating or non-heart-beating organ procurement from patients with impaired consciousness is de facto a concealed practice of physician-assisted death, and therefore, violates both criminal law and the central tenet of medicine not to do harm to patients. Society must decide if physician-assisted death is permissible and desirable to resolve the conflict about procuring organs from patients with impaired consciousness within the context of the perceived need to enhance the supply of transplantable organs
Long-term efficacy of botulinum toxin A for treatment of blepharospasm,hemifacial spasm, and spastic entropion: a multicentre study using two drug-dose escalation indexes
PURPOSE: To investigate the long-term effectiveness and safety of botulinum
neurotoxin A (BoNT-A) treatment in patients with blepharospasm (BEB), hemifacial
spasm (HFS), and entropion (EN) and to use for the first time two modified indexes, 'botulin toxin escalation index-U' (BEI-U) and 'botulin toxin escalation
index percentage' (BEI-%), in the dose-escalation evaluation. METHODS: All
patients in this multicentre study were followed for at least 10 years and main
outcomes were clinical efficacy, duration of relief, BEI-U and BEI-%, and
frequency of adverse events. RESULTS: BEB, HFS, and EN patients received a mean
BoNT-A dose with a significant inter-group difference (P<0.0005, respectively).
The mean (+/-SD) effect duration was statistically different (P=0.009) among
three patient groups. Regarding the BoNT-A escalation indexes, the mean (+/-SD)
values of BEI-U and BEI-% were statistically different (P=0.035 and 0.047,
respectively) among the three groups. In BEB patients, the BEI-% was
significantly increased in younger compared with older patients (P=0.008). The
most frequent adverse events were upper lid ptosis, diplopia, ecchymosis, and
localized bruising. CONCLUSIONS: This long-term multicentre study supports a high
efficacy and good safety profile of BoNT-A for treatment of BEB, HFS, and EN. The
BEI indexes indicate a significantly greater BoNT-A-dose escalation for BEB
patients compared with HFS or EN patients and a significantly greater BEI-% in
younger vsolder BEB patients. These results confirm a greater efficacy in the
elderly and provide a framework for long-term studies with a more flexible and
reliable evaluation of drug-dose escalation
Cildb: a knowledgebase for centrosomes and cilia
Ciliopathies, pleiotropic diseases provoked by defects in the structure or function of cilia or flagella, reflect the multiple roles of cilia during development, in stem cells, in somatic organs and germ cells. High throughput studies have revealed several hundred proteins that are involved in the composition, function or biogenesis of cilia. The corresponding genes are potential candidates for orphan ciliopathies. To study ciliary genes, model organisms are used in which particular questions on motility, sensory or developmental functions can be approached by genetics. In the course of high throughput studies of cilia in Paramecium tetraurelia, we were confronted with the problem of comparing our results with those obtained in other model organisms. We therefore developed a novel knowledgebase, Cildb, that integrates ciliary data from heterogeneous sources. Cildb links orthology relationships among 18 species to high throughput ciliary studies, and to OMIM data on human hereditary diseases. The web interface of Cildb comprises three tools, BioMart for complex queries, BLAST for sequence homology searches and GBrowse for browsing the human genome in relation to OMIM information for human diseases. Cildb can be used for interspecies comparisons, building candidate ciliary proteomes in any species, or identifying candidate ciliopathy genes
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