4 research outputs found
Neonatal and Pediatric Organ Donation: Ethical Perspectives and Implications for Policy
The lifesaving processes of organ donation and transplantation in neonatology and pediatrics carry important ethical considerations. The medical community must balance the principles of autonomy, nonmaleficence, beneficence, and justice to ensure the best interest of the potential donor and to provide equitable benefit to society. Accordingly, the US Organ Procurement and Transplantation Network (OPTN) has established procedures for the ethical allocation of organs depending on several donor-specific and recipient-specific factors. To maximize the availability of transplantable organs and opportunities for dying patients and families to donate, the US government has mandated that hospitals refer potential donors in a timely manner. Expedient investigation and diagnosis of brain death where applicable are also crucial, especially in neonates. Empowering trained individuals from organ procurement organizations to discuss organ donation with families has also increased rates of consent. Other efforts to increase organ supply include recovery from donors who die by circulatory criteria (DCDD) in addition to donation after brain death (DBD), and from neonates born with immediately lethal conditions such as anencephaly. Ethical considerations in DCDD compared to DBD include a potential conflict of interest between the dying patient and others who may benefit from the organs, and the precision of the declaration of death of the donor. Most clinicians and ethicists believe in the appropriateness of the Dead Donor Rule, which states that vital organs should only be recovered from people who have died. The medical community can maximize the interests of organ donors and recipients by observing the Dead Donor Rule and acknowledging the ethical considerations in organ donation
Influence of PARP-1 Polymorphisms in Patients after Traumatic Brain Injury
Poly(ADP-ribose) polymerase-1 (PARP-1) plays an important role in the cellular
response to stress and DNA damage. However, excessive activity of PARP-1
exacerbates brain injury via NAD+ depletion and energy failure. The
purpose of this study was to determine if tagging single nucleotide
polymorphisms (tSNPs) covering multiple regions of the PARP-1
gene are related to outcome after traumatic brain injury (TBI) in humans. DNA
from 191 adult patients with severe TBI was assayed for four tSNPs corresponding
to haplotype blocks spanning the PARP-1 gene. Categorization as
favorable or poor outcome was based on Glasgow Outcome Scale (GOS) score
assigned at 6 months. PARP-1 enzyme activity was indirectly evaluated by
quantifying poly-ADP-ribose (PAR)-modified proteins in cerebrospinal fluid (CSF)
using an enzyme-linked immunosorbent assay. In multiple logistic regression
analysis controlling for age, initial Glasgow Coma Scale score, and gender, the
AA genotype of SNP rs3219119 was an independent predictor of favorable
neurologic outcome. This SNP tags a haplotype block spanning the
automodification and catalytic domains of the PARP-1 gene. SNP
rs2271347 correlated with CSF PAR-modified protein level. This SNP, which did
not correlate with outcome, tags a haplotype block spanning the promoter region
of the PARP-1 gene. We conclude that after severe TBI in
humans, a PARP-1 polymorphism within the
automodification-catalytic domain is associated with neurological outcome, while
a polymorphism within the promoter region was associated with CSF PAR-modified
protein level. These findings must be replicated in a prospective study before
the relevance of PARP-1 polymorphisms after TBI can be
established