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PubMed1993

Non-heart-beating donors of organs: are the distinctions between direct and indirect effects & between killing and letting die relevant and helpful?

This essay analyzes the principle of double effect and, to a lesser extent, the distinction between killing and letting die in the context of the Pittsburgh protocol for managing patients who may become non-heart-beating donors or sources of organs for transplantation. It notes several ambiguities and unresolved issues in the Pittsburgh protocol but concludes that neither the principle of double effect nor the distinction between killing and letting die (with the prohibition of the former and the allowance of the latter under some circumstances) erects insurmountable obstacles to the implementation of the protocol. Nevertheless, the requirement of the principle of double effect that the intended good effects outweigh the unintended side effects necessitates careful attention to the probable overall impact of the proposed policy on organ procurement, particularly because public mistrust plays such a significant role in limiting the number of organ donations.

Cause of Death↗

PubMed2006

Psychosocial evaluation of candidates for living related kidney donation.

Living kidney donation has raised practical and ethical questions since renal transplantation became possible 50 years ago. Nevertheless, living donors are a common source for badly needed organs in the pediatric population. The safety and well being of the living donor are important concerns. Among the risks of living donation are those of a psychological and social nature. To protect these donor interests, psychosocial evaluations of donors are done at some transplant centers, but there is a lack of consistency regarding standardization of the evaluation, the content of the evaluation, and the role of the interviewer. Goals of the overall living donor evaluation for kidney transplantation at The Children's Hospital of Philadelphia, and the components of the psychosocial evaluation protocol in particular, are presented. The protocol's strengths are discussed, including the standardization of evaluations for all potential donors; the broad spectrum of psychosocial domains assessed; the psychometric measures administered; the systematic handling of negative results and some donors' desire to opt out; and the protection of confidentiality. Future directions with regard to long-term psychosocial outcomes and research protocols are discussed.

Adolescent↗

PubMed1999

Improving the approach to organ donation: a review.

Organ transplantation continues to be hindered by a limited supply of organs. A significant percentage of potential organ donors are lost to either medical failure or inability to obtain consent for donation. In a surgical intensive care unit (ICU) we have refocused our efforts toward aggressive resuscitation, directed by control of coagulopathy, invasive monitoring, and dedicated ICU management while implementing a rapid brain death determination protocol. Over a 6-year period the length of stay until the legal determination of brain death is made has been significantly shortened (12.0 vs. 3.4 hours; p < 0.05), as have associated charges despite this more aggressive approach. As a result, we have eliminated medical failures prior to donation (13% vs. 0%) and increased consent rates (44% vs. 71%; p < 0.05). These efforts have significantly improved the number of organs harvested per eligible donor (1.8 vs. 3.4; p < 0.05). In addition, the number of organs per actual donor has increased and is now markedly greater than the U.S. national average (4.7 vs. 3.7). We believe the approach presented, if widely applied, could potentially improve the current organ supply shortage.

Blood Coagulation Disorders↗

PubMed2003

Stem therapy for ALS: hope and reality.

All are agreed that there is pressing need for an effective treatment for Amyotrophic Lateral Sclerosis (ALS; MND). Such treatment may derive from a combination of therapeutic strategies aimed at different aspects of the disorder, and might include drugs directed at the initial, intermediate or terminal cascade of events leading to cell death, as well as the use of stem cells to replace dead motor neurons, or to protect those that remain. The attraction of cell implantation or transplantation is that it might help to overcome the inability of the CNS to replace lost neurons. It is also clear that neural implantation will yield little benefit if the donor cells fail to integrate functionally into the recipient CNS circuitry. In this respect, ALS poses an especially difficult problem. The recent breakthroughs in stem cell research might nevertheless provide possibilities for neural implantation and cell replacement therapy for patients with ALS. The potential impact of these new approaches to neurodegenerative diseases has been emphasised by the many experiments using human foetal cell grafts in patients affected by Parkinson's and Huntington's disease. Clinical benefits in Parkinson's disease seem to be associated with integration of the donor cells into the recipient brain. Despite promising results, however, significant constraints have hampered the use of foetal cells for neural implantation and transplantation. Besides ethical concerns, the viability, purity, and final destiny of the foetal tissue have not been completely defined. Foetal cells are, in addition, post-mitotic and cannot be expanded or stored for long periods, necessitating close synchronisation of tissue donation and neurosurgery.

Amyotrophic Lateral Sclerosis↗

PubMed2004

Cost-effectiveness of organ donation: evaluating investment into donor action and other donor initiatives.

Initiatives aimed at increasing organ donation can be considered health care interventions, and will compete with other health care interventions for limited resources. We have developed a model capable of calculating the cost-utility of organ donor initiatives and applied it to Donor Action, a successful international program designed to optimize donor practices. The perspective of the payer in the Canadian health care system was chosen. A Markov model was developed to estimate the net present value incremental lifetime direct medical costs and quality adjusted life years (QALYs) as a consequence of increased kidney transplantation rates. Cost-saving and cost-effectiveness thresholds were calculated. The effects of changing the success rate and time frame of the intervention was examined as a sensitivity analysis. Transplantation results in a gain of 1.99 QALYs and a cost savings of Can$104,000 over the 20-year time frame compared with waiting on dialysis. Implementation of an intervention such as Donor Action, which produced as few as three extra donors per million population, would be cost-effective at a cost of Can$1.0 million per million population. The cost-effectiveness of Donor Action and other organ donor initiatives compare favorably to other health care interventions. Organ donation may be underfunded in North America.

Canada↗

PubMed1998

Curriculum effect on nursing students' attitudes and knowledge towards organ donation and transplantation.

OBJECTIVE: To determine the impact of a nursing school's curriculum on student nurses' attitudes towards organ donation and whether specific educational directives could improve these attitudes. DESIGN: Quasi-experimental. SAMPLE/SETTING: First-, third-, and fourth-year nursing students at a Canadian University School of Nursing. METHODS: A questionnaire was developed to measure student's attitudes towards organ donation and transplantation. The questionnaire was administered to first- and fourth-year students to determine whether 4 years of nursing education changed the attitudes of the students. Third-year students responded to the questionnaire before and after attending a lecture or lecture and small group sessions on organ donation to determine whether instruction could improve attitudes and knowledge. RESULTS: No difference in attitudes were found between first- and fourth-year nursing students. The introduction of specific education strategies improved the attitudes and knowledge base of third year students. Discussion sessions in addition to lecture were the preferred strategy. CONCLUSIONS: The present curriculum does not significantly impact on nursing students. Given the importance of organ transplantation, nursing curricula should incorporate effective strategies to teach students the role of the nurse in organ donation.

Curriculum↗

PubMed2000

[Screening for markers of infections transmitted by transfusions in the blood collected in France from 1996 to 1998].

From 1996 to 1998, a decrease in positive donation rates has been observed for HIV, HCV and HBs Ag in first-time donors, while these rates remained stable for HTLV. In repeat donors, the same decrease was observed for HCV and HBs Ag while the rates remained stable for HIV. No HTLV-positive donations from repeat donors were noted in 1998. About half of the HIV-positive repeat donors were regular donors (less than two years between the two donations), as well as 88% of HBV-infected repeat donors. Inversely, only 20% of HCV-positive repeat donors were regular donors. Anti-HBc antibodies have been found in 20% of HIV-infected donors, in 22% of HCV-infected donors, and were associated with HBs Ag in 99% of the cases. Elevated ALT was observed in 47% of donors with anti-HCV and in 10% of donors with HBs Ag. The major risk factors are at-risk sexual behavior for HIV and use of intravenous drugs and nosocomial infections for HCV. Being a native of an endemic country has been found to be the major risk for HBV. The major HTLV risk factor was directly or indirectly linked to the Caribbean area.

Biomarkers↗

PubMed2006

Utilizing list exchange and nondirected donation through 'chain' paired kidney donations.

In a list exchange (LE), the intended recipient in an incompatible pair receives priority on the deceased donor waitlist (DD-waitlist) after the paired incompatible donor donates a kidney to a DD-waitlist candidate. A nondirected donor's (ND-D) kidney is usually transplanted directly to a DD-waitlist candidate. These two established practices would help even more transplant candidates if they were integrated with kidney paired donation (KPD). We consider a scenario in which the donor of an LE intended recipient (LE-IR) donates to a compatible KPD intended recipient (KPD-IR), and the KPD donor (KPD-D) donates to the waitlist (an LE-chain). We consider a similar scenario in which an ND-D donates to a KPD-IR and the KPD-D donates to the DD-waitlist (an ND-chain). Using data derived from the New England Program for Kidney Exchange (NEPKE) and from OPTN/SRTR recipient-donor distributions, simulations are presented to evaluate the potential impact of chain exchanges coordinated with KPD. LE donors (LE-D) and ND-D who are ABO-O result in the highest number of additional transplants, while results for ABO-A and B donors are similar to each other. We recommend that both LE and ND donations be utilized through chain exchanges.

ABO Blood-Group System↗

PubMed2005

The cannabinoid CB1 receptor antagonist rimonabant (SR141716) inhibits cell proliferation and increases markers of adipocyte maturation in cultured mouse 3T3 F442A preadipocytes.

Adipocyte cell proliferation is an important process in body fat mass development in obesity. Adiponectin or Acrp30 is an adipocytokine exclusively expressed and secreted by adipose tissue that regulates lipid and glucose metabolism and plays a key role in body weight regulation and homeostasis. Adiponectin mRNA expression in adipose tissue and plasma level of adiponectin are decreased in obesity and type 2 diabetes. In obese rodents, the selective CB(1) receptor antagonist rimonabant reduces food intake and body weight and improves lipid and glucose parameters. We have reported previously that rimonabant stimulated adiponectin mRNA expression in adipose tissue of obese fa/fa rats, by a direct effect on adipocytes. We report here that rimonabant (10-400 nM) inhibits cell proliferation of cultured mouse 3T3 F442A preadipocytes in a concentration-dependent manner. In parallel to this inhibitory effect on preadipocyte cell proliferation, rimonabant (25-100 nM) stimulates mRNA expression and protein levels of two late markers of adipocyte differentiation (adiponectin and glyceraldehyde-3-phosphate dehydrogenase) with a maximal effect at 100 nM, without inducing the accumulation of lipid droplets. Furthermore, treatment of mouse 3T3 F442A preadipocytes with rimonabant (100 nM) inhibits basal and serum-induced p42/44 mitogen-activated protein (MAP) kinase activity. These results suggest that inhibition of MAP kinase activity by rimonabant may be one of mechanisms involved in the inhibition of 3T3 F442A preadipocyte cell proliferation and stimulation of adiponectin and GAPDH expression. The inhibition of preadipocyte cell proliferation and the induction of adipocyte late "maturation" may participate in rimonabant-induced antiobesity effects, particularly the reduction of body fat mass.

Adipocytes↗

PubMed2000

Hormonal changes in brain death and immune activation in the donor.

Kidneys obtained from brain dead donors show inferior graft survival compared to living donation. The effects of brain death itself are thought to be partly responsible for these results. We, therefore, examined levels of catecholamines, the vasoconstricting hormones AT II, ET-1 and renin activity, pituitary hormones, and their correlation to pro-inflammatory cytokines and cytokine receptors. In 17 brain dead patients and 19 preoperative neurosurgical patients, these parameters were measured by HPLC, RIA and ELISA. Brain death resulted in massive increases in serum catecholamines, AT II and ET-1, as well as PRA, whereas thyroid and adrenal hormone levels remained unchanged. We found a significant correlation with rises in IL-6 and soluble TNF and IL-2 receptors as markers for the activation of immunological cascades. We concluded that these effects could be directly and indirectly responsible for the impaired organ perfusion and function observed in brain death.

Adult↗

PubMed2006

Training for doctors and nurses to deal with bereaved relatives after a sudden death: evaluation of the European Donor Hospital Education Programme (EDHEP) in Germany.

The sudden death of a person is one of the most extreme and painful experiences for the relatives, and doctors require special communication skills to deal adequately with the bereaved. The Dutch European Donor Hospital Education Programme was developed to train doctors and nurses in talking to the bereaved relatives and to make the donation request. In Germany, the one-day workshop has been adapted to the German language, law, and clinical practice. The evaluation data of 75 workshops and experiences of 760 participants (doctors, nurses, and psychologists) are reported. The framework of, methods used, and issues dealt with in the workshop were clearly appreciated by the great majority of the participants. Criticisms and suggestions were directed mainly at the duration of the workshop. One third of the participants pleaded for a 2-day workshop, two thirds for a refresher course half a year later. The main effects reported were that two thirds of the participants rated that relatives could be helped, talked with, and cared for in a better way. The workshop participants also reported that they themselves were better able to cope with the situation and were more inclined to take on the task following the workshop. Finally, the necessities and limits of psychosocial training for doctors and their staff are discussed.

Bereavement↗

PubMed2005

Organ donation and utilization in the United States, 2004.

This article discusses issues directly related to the organ donation process, including donor consent, donor medical suitability, non-recovery of organs, organs recovered but not transplanted, expanded criteria donors (ECD), and donation after cardiac death (DCD). The findings and topics covered have important implications for how to evaluate and share best practices of organ donation as implemented by organ procurement organizations (OPOs) and major donor hospitals in the same donation service areas (DSAs). In 2002 and 2003, US hospitals referred more than one million deaths or imminent deaths to the OPOs of their DSA. Referrals increased by nearly 10% from 2002 to 2003 (1,022,280 to 1,121,392). Donor consents have increased by about 5% and the number of total deceased donors has risen from 6,187 to 6,455. Since multiple organs are recovered from most donors, this increase allowed more than 500 additional wait-listed candidates to receive an organ transplant than in the prior year. Non-traditional donor sources have experienced a large rate of increase; in 2003 the number of ECD kidney donors increased by 8% and the number of DCD donors increased by 43%, from 189 donors in year 2002 to 271 donors in 2003.

Ethnicity↗

PubMed2002

Routine advance directive and organ donation questioning on admission to hospital.

OBJECTIVE: The purpose of this study is to determine whether routine questioning on admission to hospital can identify patients who do not want cardiopulmonary resuscitation (CPR) or intensive-care unit (ICU) admission. We also determined whether routine questioning can identify patients interested in organ donation. Finally, we determined whether routine questioning helps train housestaff to discuss end-of-life issues with patients. METHODS: The housestaff of an internal-medicine ward questioned admitted patients about previous discussions regarding resuscitation or organ donation, and about preferences regarding CPR, ICU, and organ donation. RESULTS: Of 40 patients who had never discussed CPR and ICU issues, 25 per cent preferred no CPR, and 18 per cent preferred no ICU. Of 24 patients who had never discussed organ-donation issues, 67 per cent were interested in being donors. All housestaff felt more comfortable discussing end-of-life issues by the end of the study. CONCLUSION: Routine questioning of patients on admission identifies a significant number who prefer no CPR or ICU. This information may help to avoid inappropriate resuscitation efforts and ICU admissions. Routine questioning also reveals many patients who are interested in organ donation. Encouraging these patients to identify themselves and to discuss their wishes with family members may increase the number of procurable organs. Housestaff benefit from the experience of discussing end-of-life issues.

Advance Care Planning↗

PubMed1994

The toxic patient as a potential organ donor.

The use of organs from poisoned victims for the purpose of transplantation has been poorly studied; criteria for organ donation is virtually non-existent in such cases. To further elucidate these indications, a retrospective review of all organ transplantation donated by poisoned victims in Northern and Central Illinois was undertaken. From January 1988 to December 1993, 17 poisoned victims were identified as having donated organs to 41 recipients. Eleven of the donors died as a direct result of drug toxicity, whereas six donors had drug-related deaths. The cases were reviewed for toxin involved, organ preoperative function and postoperative function (up to 1 year after transplant). Kidney transplants postoperative function was rated as good if creatinine was less than 1.9, fair if creatinine was 2 to 2.9, and poor if creatinine was 3. Donor age ranged from 2 years to 54 years. Toxins involved in donation included ethanol (n = 8), cocaine (n = 5), carbon monoxide (5), barbiturates (2) and lead (1), six patients had multiple drugs. Two of the nine recipients of livers died intraoperatively, both unrelated to organ function. Thirty-two kidneys were transplanted with 28 having good 10-day postoperative function, three having fair postoperative function, and one (cocaine donor) having poor postoperative function. One kidney transplanted from a cocaine donor had a thrombosed graft 5 days postoperatively. Deaths involving toxins in general does not seem to be a contraindication to donation of liver and kidney for transplantation.

Adolescent↗

PubMed2005

Patient-specific embryonic stem cells derived from human SCNT blastocysts.

Patient-specific, immune-matched human embryonic stem cells (hESCs) are anticipated to be of great biomedical importance for studies of disease and development and to advance clinical deliberations regarding stem cell transplantation. Eleven hESC lines were established by somatic cell nuclear transfer (SCNT) of skin cells from patients with disease or injury into donated oocytes. These lines, nuclear transfer (NT)-hESCs, grown on human feeders from the same NT donor or from genetically unrelated individuals, were established at high rates, regardless of NT donor sex or age. NT-hESCs were pluripotent, chromosomally normal, and matched the NT patient's DNA. The major histocompatibility complex identity of each NT-hESC when compared to the patient's own showed immunological compatibility, which is important for eventual transplantation. With the generation of these NT-hESCs, evaluations of genetic and epigenetic stability can be made. Additional work remains to be done regarding the development of reliable directed differentiation and the elimination of remaining animal components. Before clinical use of these cells can occur, preclinical evidence is required to prove that transplantation of differentiated NT-hESCs can be safe, effective, and tolerated.

Adult↗

PubMed2006

Assessing medical student knowledge, attitudes, and behaviors regarding organ donation.

PURPOSE: To measure medical students' knowledge of the central issues in organ donation and transplantation and to understand their perception of the extent of training they received prior to and during medical school. METHODS: A previously validated, 41-question instrument assessing organ donation, allocation, and transplantation knowledge was directly administered to 537 first- and second-year medical students attending one of three Ohio schools from January through April 2005. Students were also asked about their support for organ donation and the donation training they had received. RESULTS: Two hundred sixty four first-year and 236 second-year students responded (response rate = 93%). Few students to date received donation and transplantation training before (11%) or during (22%) medical school. Second-year students were more likely than first-year students to have received training during medical school (40% vs 6%, P < .001) and to have read articles regarding donation (24% vs 15%, P = .017). However, both first- and second-year medical students answered the majority of the knowledge questions incorrectly (43% vs 48%, P < .002). Knowledge regarding brain death was lower among medical students compared to a random sample of Ohio adults (P < .001). Donation coursework prior to or during medical school was significantly associated with an increased knowledge regarding donation (odds ratio [OR] = 2.01, P = .001) and knowing where to find answers to patients' questions regarding donation (OR = 2.76, P < .001). CONCLUSION: Medical students have significant gaps in knowledge regarding the organ donation and transplantation system. Donation and transplantation education is associated with improved knowledge in the area and comfort in knowing how to address patient questions.

Adult↗

PubMed2002

Attitudes regarding organ donation from non-heart-beating donors.

PURPOSE: To determine the attitudes toward organ donation from non-heart-beating cadaver donors in a sample of the general public and health care workers. MATERIALS AND METHODS: A moderator-administered questionnaire was completed by members of the general public, recruited randomly from a professional consumer research group's database, and health care workers recruited from the same database, family practice clinics, and local hospitals. Two primary scenarios were tested: (1) patient in coma, not going to survive intensive care unit (ICU), and (2) patient lapsing in and out of consciousness, lifetime institutional care. RESULTS: Sixty members of the general public and 68 health care workers completed the questionnaire. The majority of both groups were aware life support could be withdrawn in Scenario 1, however, significantly fewer were aware life support could also be withdrawn in Scenario 2 (83% general public vs 34% general public, P <.001 and 94% health care workers vs 78% health care workers, P =.012). Uncertainty in prognosis was cited as the primary concern. The issue of organ donation was directly linked with withdrawal of life support. The majority of both groups believed that organ donation would be permissible if further life support were deemed to be not in the patient's best interest because of poor short-term prognosis (94% health care workers and 98% general public for Scenario 1 and 87% health care workers and 81% general public for Scenario 2). The greatest difficulty arose in defining futility of care. Expected quality of life, patient's and family's values, opinions, and religious beliefs were felt to be most important in determining decisions regarding futility and withdrawal of life support. Physician beliefs and values were felt to influence decisions more than they should. CONCLUSIONS: Both the general public and health care workers support the use of non-heart-beating cadaver donors once a decision has been made to withdraw life support. However, both groups raised concerns regarding how the decision to withdraw life support is made.

Attitude of Health Personnel↗

PubMed1998

Is the male involved in the aetiology of ectopic pregnancy?

We have previously observed a low incidence of ectopic pregnancies in couples having gamete intra-Fallopian transfer (GIFT) with donated spermatozoa. Based on findings in both animal and human models, we proposed the hypothesis that sperm defects may be associated with the expression of paternal genes which cause abnormal early embryo development and predispose the embryos to interact inappropriately with the genital tract epithelium, and so increase the risk of an ectopic implantation. To both confirm and extend the initial observation, GIFT and in-vitro fertilization (IVF) pregnancies entered on the Australian and New Zealand national database between 1979 and 1993 were analysed with regard to the incidence of ectopic pregnancy. There was an increased risk of ectopic pregnancy for IVF relative to GIFT and when spermatozoa from the male partner were used rather than donor spermatozoa. However, when couples were categorized with respect to the aetiology of their infertility, we were unable to show a significant association between ectopic pregnancy and whether spermatozoa from the male partner or a donor were used. We have therefore been unable to confirm a direct association between the source of spermatozoa and ectopic pregnancy.

Female↗