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Transplantation and Organ Donation
Published in Ian Greaves, Keith Porter, Jeff Garner, Trauma Care Manual, 2021
Ian Greaves, Keith Porter, Jeff Garner
The numbers of patients certified as deceased via brainstem criteria in the UK has remained low, producing a limited potential donor pool. This has led to a resurgence of interest in donation from those patients certified deceased through cardiorespiratory criteria (essentially asystolic donors). This has been supported by advances in immunosuppression, and combining this with careful patient selection, minimization of warm ischaemic times and evaluation of organ function produces organs whose function is almost as good as those from brainstem dead donors. Identification of this potential pool of donors was supported by the publication of UK guidance on non-heart beating donation from the Intensive Care Society in 20055 and the Academy of Medical Royal Colleges guidance on certification of death in 2008.6 In the same year the organ donation taskforce published its report on organ donation, aiming to increase cadaveric donation by 50% over the subsequent 5 years, especially by introducing specialist nurses in organ donation in hospitals screening potential donors. This was achieved almost entirely due to massive expansion in DCD (Donation after Circulatory Death) donors, which now stand at around 650 donors annually (in comparison to 53 in 2002). However, in 2018 there remained over 6,000 patients waiting for organ donation in the UK, with more than a thousand people annually who either die whilst waiting for a transplant or become too ill to receive one.7
Organ transplantation
Published in Marc Stauch, Kay Wheat, Text, Cases and Materials on Medical Law and Ethics, 2018
What, by contrast, is regarded as ethically and legally acceptable is the continuing life-support of patients initially placed on the ventilator on therapeutic grounds, in order to prolong the dying process until the transplant team is on hand (extraction will then take place once brainstem death has been diagnosed, including – in an increasing number of cases – after cessation of ventilation as a ‘non-heart-beating donation’).33 In these cases, where the incapable, dying patient previously expressed the wish to be an organ donor, such measures may be considered in their best interests, which, as per the 2005 Mental Capacity Act, may be influenced by the patient’s previous wishes and values.34 In this context, the Department of Health’s Organ Donation Taskforce, in its 2008 Report, Legal issues relevant to non-heartbeating donation, advises as follows: As regards the Human Tissue Act 2004, this specifically allows, in s 43, for doctors to take steps to preserve cadaveric organs for transplantation. However, this provision is directed to potential donors whose death has already been confirmed: it relates to the legality of measures taken after this point, but before ‘appropriate consent’ has been obtained to the organs’ removal and use: see further 11.3.3.2 below.
Urological and Biochemical Aspects of Transplantation Biology
Published in Anthony R. Mundy, John M. Fitzpatrick, David E. Neal, Nicholas J. R. George, The Scientific Basis of Urology, 2010
The early transplants were all performed from live donors; then, with the advent of immunosuppression, nonrelated cadaver donors could be used. These initially were simply cadavers and therefore were “non–heart beating” donors, but later, with legislation and acceptance of brain death, heart-beating but brain-dead donors were used. More recently, with the limited supply of brain-dead donors, there has been significant expansion of both live donation and non–heart beating donation.
Novel topoisomerase II/EGFR dual inhibitors: design, synthesis and docking studies of naphtho[2′,3′:4,5]thiazolo[3,2-a]pyrimidine hybrids as potential anticancer agents with apoptosis inducing activity
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Mai A. E. Mourad, Ayman Abo Elmaaty, Islam Zaki, Ahmed A. E. Mourad, Amal Hofni, Ahmed E. Khodir, Esam M. Aboubakr, Ahmed Elkamhawy, Eun Joo Roh, Ahmed A. Al-Karmalawy
According to lipinskiʼs rule of five, the molecule is considered to be orally active if it obeys the following criteria: (i) lipophilicity or the calculated octanol–water partition coefficient (LogP) ≤ 5, (ii) molecular weight (Mwt) ≤ 500, (iii) number of hydrogen bonds donors (nHBD) ≤ 5, (iv) number of hydrogen bonds acceptors (nHBA) ≤ 10. Moreover, veber’s criteria involving: topological polar surface area (TPSA) < 140 Å and number of rotatable bonds (nRB) < 10. Notably, violation of more than one of these rules indicating bioavailability problems53. Gratefully, the results displayed in Table 6 showed that all the synthesised hybrids possessed desirable physicochemical properties with no Lipinski property violations. Noteworthy, Log P of the studied hybrids was in the range of (2.93–4.09) indicating good lipophilicity and permeability across the cell membrane. Additionally, these hybrids can be easily transported and absorbed through the biological membranes where the Mwt was less than 500 Da. Meanwhile, the number of hydrogen bond donors and acceptors were less than 5 and 10, respectively, which was in compliance with Lipinski’s rules.
The Dead Donor Rule Does Require that the Donor is Dead
Published in The American Journal of Bioethics, 2023
Robertson also asserts that the DDR requires that the prospective donor is dead in the case of “non-heart-beating donors” (NHBD) which today are called donors after circulatory death (Robertson 1999). Robertson considers two controversies: first, whether interventions prior to the declaration of death in order to preserve organs is permissible; and second, whether NHBD “allow retrieval of organs before cessation of pulmonary function is irreversible” (Robertson 1999, 11). Here, I focus on the second controversy, where Robertson is concerned that “[t]he risk is that death will be pronounced so quickly after the removal of life support and induction of cardiac arrest that the person will not have irreversibly lost cardiac function and thus will still be alive when organs are removed” (Robertson 1999, 11). That is, Robertson is concerned because the DDR does require that persons be determined dead before organ procurement, or the procurement may be the cause of death which would violate the DDR (Robertson 1999, 11). Robertson next explores what is needed to say that the person has irreversibly lost all cardiopulmonary function. He distinguishes between physiologically irreversible (which he does not believe has been achieved after a five-minute hands-off period because persons have been resuscitated after five minutes of downtime) and morally/legally irreversible (because there is no plan to resuscitate out of respect for the patient’s wishes). Robertson then concludes, “The use of NHBDs….is morally and legally acceptable because of their careful attempt to respect the dead donor rule. The debate over the use of NHBDs, however, illustrates the strong opposition that probably would exist if vital organs were taken from non-heart-beating donors who were not dead…” (Robertson 1999, 12–13).