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Potential psychological attachments formed by donors involved in fertility technology--another side to infertility.

Donor participation has become an integral component in the treatment of infertility. While the donors' reproductive capabilities continue to be utilized to support fertility technology, little effort has been directed at understanding the experience of these participants. Based on attachment theory, it can be argued that donors have the potential to form parent-offspring attachments. This bonding may result in psychological sequelae from the separation inherent in technology that disconnects the genetic, gestational and social functions of parenthood. Implications for health care providers involved in infertility care are discussed.

Counseling↗

NCX 4016, a nitric oxide-releasing aspirin, modulates adrenergic vasoconstriction in the perfused rat tail artery.

1. The ability of the nitric oxide (NO)-releasing aspirin, NCX 4016, to control vasoconstrictor responses induced by electrical field stimulation (TNS) or by exogenous norepinephrine (NE) was investigated in perfused rat tail artery with intact endothelium. 2. NCX 4016 (25, 50 and 100 microM) dose-dependently antagonized the vasoconstriction caused by TNS (from 0.5 to 64 Hz) and by NE (from 0.01 to 10 microM). The vasorelaxant activity of NCX 4016 (100 microM) in NE-precontracted arteries was concomitant with a marked increase of tissue cyclic GMP (4.9 fold, P<0.001) and was significantly antagonized by the inhibitors of soluble guanylate cyclase, methylene blue and 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one. 3. The effect of NCX 4016 was endothelium NO-independent since, in preparations perfused with N(G)-monomethyl-L-arginine (10 microM), this compound prevented the rise in basal perfusion pressure and reversed the accentuation of vasoconstrictor responses caused by NO synthase inhibition. 4. Aspirin-moiety released by NCX 4016 inhibited the 6-keto-PGF(1alpha) formation without interfering with the vasorelaxant activity of NCX 4016, while aspirin (100 microM) was devoid of any activity against vasoconstriction induced by both TNS and NE in perfused rat tail artery. 5. NCX 4016 moderated adrenergic vasoconstriction in perfused rat tail arteries by a direct donation of NO without involving the relaxant factors such as PGI(2) and NO from endothelial cells. 6. The results obtained with NCX 4016 in perfused rat tail artery bears some therapeutical potential in conditions associated with vascular smooth muscle hyperreactivity to adrenergic stimulation.

Animals↗

Living domino liver transplantation in an adult with congenital absence of portal vein.

Congenital absence of the portal vein (CAPV) is a rare malformation of the splanchnic venous system. Although CAPV is usually detected in the pediatric age group, our patient was a 35-year-old woman. She had been diagnosed with CAPV in 1996 when she was 27 years old. In 1998, she was placed on hemodialysis due to chronic renal failure. After several episodes of encephalopathy in 2002, liver transplantation (LT) was recommended to her and her family. Since there was no suitable living donor candidate, she was put on the waiting list for a deceased donor liver transplant in Japan. In 2004, her ammonia level increased to around 300 microg/dl, and she went into a coma lasting for three days. After recovering from this event, she underwent a living domino transplantation using a whole liver donated by a familial amyloid polyneuropathy (FAP) patient. Her portal vein, which had drained directly into the inferior vena cava (IVC), was transected together with a cuff of the IVC wall and anastomosed to the graft liver portal vein in an end-to-end fashion. In conclusion, liver transplantation proved to be a safe and effective way to save this patient and improve her quality of life.

Adult↗

Co-oxidation of xenobiotics: lipid peroxyl derivatives as mediators of metabolism.

Systems which carry out peroxyl-dependent oxidations can serve as activation systems for carcinogenic compounds. Some function via classical peroxidase reactions in which an enzyme-derived oxidant performs the electron abstraction from or oxygen donation to the oxidizable substrate. This mechanism applies to the peroxidative activation of aromatic amines and of the phenolic compound diethylstilbestrol. These classical peroxidase reactions may be initiated by hydrogen peroxide or by organic peroxides, including lipid hydroperoxides. A different mechanism is involved in the oxygenation of polycyclic aromatic hydrocarbons and of aflatoxin B1. In these cases the oxidant is a peroxyl radical, and the reaction occurs by the direct, non-enzymatic interaction of the peroxyl radical and the oxidizable substrate. Most peroxyl radicals in biological systems are lipid-derived. The key reaction which distinguishes the peroxyl radical-dependent oxidations from the classical peroxidase reactions is the ability of the former to epoxidize activated carbon-carbon double bonds. The epoxidation of benzo[a]pyrene derivatives has been studied extensively in subcellular and whole cell and tissue systems, and is discussed as a model for this class of reaction. Determining the generality of this activation path and its role in vivo present the major questions to be answered in regard to the importance of these reactions in chemical carcinogenesis.

Biotransformation↗

Criteria for death: self-determination and public policy.

'Whole brain death' criteria have found support in Western cultures in regard to post-mortem organ donation and the termination of care for patients meeting these strict criteria. But they are of minimal use in Asian cultures and in the ethics of caring for the persistent vegetative patient. This paper introduces a formula for a global Uniform Determination of Death statute, based on the 'entire brain including brain stem' criteria as a default position, but allowing competent adults by means of advance directives to choose other criteria for determining death during the process of dying.

Bioethics↗

Governing stem cell research in California and the USA: towards a social infrastructure.

Owing to the restrictive human embryonic stem cell (hESC) policies of the US government, the question of whether to pursue human embryonic stem cell experiments has dominated the ethical and political discourse concerning such research. Explicit attention must now turn to problems of implementing the research on a large scale: in the 2004 US elections, California voters approved a state initiative for stem cell research, earmarking $3 billion in direct spending over 10 years. This article explores three ethical and political problem areas emerging out of the California program, the resolution of which will help set the trajectory of hESC research in the US and abroad, and then proposes an institutional approach to help address them: a network of public stem cell banks in the US that feature transparent and shared governance.

California↗

Role of platelets in cholesteryl ester formation by U-937 cells.

The conversion of tissue macrophages into cholesteryl ester-rich foam cells is a crucial early event in atherogenesis. We studied the platelet as a potential source of cholesterol for esterification by macrophages because (a) platelets are rich in free cholesterol, (b) they adhere to macrophages early in atherogenesis, and (c) vascular injury can induce foam cell formation in the absence of hyperlipoproteinemia. We found that washed, activated human platelets from normocholesterolemic donors stimulated cholesteryl ester formation by the human monocyte-derived cell, U-937. Platelet cholesterol, released from platelets activated with calf skin collagen, was approximately equipotent at donating cholesterol to U-937 cells for esterification as normal human low density lipoprotein cholesterol. The stimulation of cholesteryl ester formation by activated human platelets demonstrated both concentration and time dependence. When hypercholesterolemic donors were studied, it was found that increasing plasma levels of cholesterol correlated directly with the ability of these hypercholesterolemic platelets to support cholesteryl ester synthesis by U-937 cells. Cholesterol-donating activity was also found in a 1,000-g supernatants of activated platelets. These observations point to a new and potentially important role for platelets in atherogenesis and suggest a mechanism for foam cell formation in the absence of marked hypercholesterolemia.

Blood Platelets↗

Issues in organ procurement: presumed consent, bioethical type II errors, and organ registries.

In an effort to alleviate the current imbalance between the many in need of an organ transplant and the limited number of organs procured, a policy of presumed consent has been recently debated. Presumed consent assumes that potential organ donors agree to donate their organs in the absence of known objections to the contrary. The authors examine the bioethical principles and consequences involved in such a policy and apply hypothesis testing, borrowed from clinical epidemiology, to a "bioethical test" of presumed consent in a hypothetical clinical scenario. A possible bioethical alternative to presumed consent, an organ donor registry of advanced directives as has been established in British Columbia, is also discussed.

Advance Directives↗

Internet-based intervention to promote organ donor registry participation and family notification.

BACKGROUND: Little is known regarding the potential of Internet-based educational interventions to increase organ donor registry participation and family notification of donation wishes. We studied the effects of an Internet-based multimedia intervention (www.journey.transweb.org) on donor registry participation and family notification. METHODS: Visitors to a specially designed web site were studied between December 14, 2000, and March 31, 2002. Demographic characteristics were requested, and a pretest was administered to one half of the participants (selected randomly) before web site content exposure. All visitors were offered a posttest. Eight knowledge questions (true/false), three attitude questions (7-point scale), and three behaviors (yes/no) were assessed. RESULTS: A total of 10,884 visitors provided demographic data. Correct answers to knowledge questions increased from 85.1% to 87.0% overall (pretest vs. posttest; P<0.001) and from 80.6% to 82.0% for teenagers (P<0.001). Willingness to donate increased (scores of 6.34 vs. 6.39; P<0.001), as did willingness to join a donor registry (scores of 5.53 vs. 5.67; P<0.001). Willingness measures were less positive among teenagers but increased significantly after exposure to the intervention. Almost 10% of visitors directly linked to an online registry and 2,489 (23%) used the web site facilities to communicate donation wishes. Increases in knowledge were not associated with changes in attitudes, but an increase in pro-donation attitude was a significant predictor of donor registry participation (P<0.001). CONCLUSIONS: Increases in donation attitudes among visitors to an organ donation web site resulted in positive behaviors, such as enrollment in a donor registry and family notification. Future efforts should focus on using Internet-based interventions to improve attitudes toward donation and to facilitate pro-donation behaviors.

Adolescent↗

L-carnosine (beta-alanyl-L-histidine) and carcinine (beta-alanylhistamine) act as natural antioxidants with hydroxyl-radical-scavenging and lipid-peroxidase activities.

Carnosine (beta-alanyl-L-histidine) and carcinine (beta-alanylhistamine) are natural imidazole-containing compounds found in the non-protein fraction of mammalian tissues. Carcinine was synthesized by an original procedure and characterized. Both carnosine and carcinine (10-25 mM) are capable of inhibiting the catalysis of linoleic acid and phosphatidylcholine liposomal peroxidation (LPO) by the O2(-.)-dependent iron-ascorbate and lipid-peroxyl-radical-generating linoleic acid 13-monohydroperoxide (LOOH)-activated haemoglobin systems, as measured by thiobarbituric-acid-reactive substance. Carcinine and carnosine are good scavengers of OH. radicals, as detected by iron-dependent radical damage to the sugar deoxyribose. This suggests that carnosine and carcinine are able to scavenge free radicals or donate hydrogen ions. The iodometric, conjugated diene and t.l.c. assessments of lipid hydroperoxides (13-monohydroperoxide linoleic acid and phosphatidylcholine hydroperoxide) showed their efficient reduction and deactivation by carnosine and carcinine (10-25 mM) in the liberated and bound-to-artificial-bilayer states. This suggests that the peroxidase activity exceeded that susceptible to direct reduction with glutathione peroxidase. Imidazole, solutions of beta-alanine, or their mixtures with peptide moieties did not show antioxidant potential. Free L-histidine and especially histamine stimulated iron (II) salt-dependent LPO. Due to the combination of weak metal chelating (abolished by EDTA), OH. and lipid peroxyl radicals scavenging, reducing activities to liberated fatty acid and phospholipid hydroperoxides, carnosine and carcinine appear to be physiological antioxidants able to efficiently protect the lipid phase of biological membranes and aqueous environments.

Antioxidants↗

Serum estradiol levels after 4 days of ovarian hyperstimulation in oocyte donors are predictive of embryo quality and clinical outcomes.

OBJECTIVE: To determine whether estradiol (E(2)) levels after 4 days of ovarian hyperstimulation in leuprolide-downregulated cycles are predictive of embryo quality and pregnancy outcome in oocyte donation. MATERIAL AND METHODS: Retrospective analysis of 287 consecutive oocyte donation cycles performed at a university assisted reproduction therapy program between January 1996 and December 2000. Oocyte donors and recipients followed a non-varied standard synchronization regimen. A serum E(2) (day-5 E(2)) was obtained from egg donors the morning after leuprolide acetate downregulation and 4 days after hMG/FSH administration. Day-5 E(2) was categorized into 3 groups: group I <75 pg/ml; group II 75-350 pg/ml, and group III > or =350 pg/ml. All embryo transfers were performed 3 days after oocyte recovery. RESULTS: Elevated day-5 E(2) levels were directly correlated with higher average embryo scores, greater number of oocytes retrieved, and greater number of embryos available for transfer and cryopreservation. Improved pregnancy outcomes were also noted for group III (day-5 E(2) level >350 pg/ml). CONCLUSION: After 4 days of gonadotropin stimulation, an E(2) level of >350 pg/ml is most predictive of higher embryo grade and pregnancy outcome in oocyte donation.

Adult↗

Age, pregnancy and miscarriage: uterine versus ovarian factors.

This study was performed to evaluate the relative contribution of oocyte and uterine factors to the age-related reduction in fecundity. The pregnancy and miscarriage rates in women receiving donated oocytes were compared to those in women using their own oocytes in in-vitro fertilization (IVF) and gamete intra-Fallopian transfer (GIFT) procedures. Oocyte donation with embryo transfer was performed on 241 women in 371 cycles; 116 of these women became pregnant (48% per patient and 31.5% per cycle) of whom 40 (35%) miscarried, giving a live birth rate of 20.5%. Assisted conception, in the form of IVF/GIFT procedures, was performed on 1331 women using their own oocytes in 2194 cycles; 627 of these women became pregnant (47% per patient and 28.7% per cycle), of whom 228 (36%) miscarried, giving a live birth rate of 18.2%. Neither the age of the donor nor the age of the recipient was related to pregnancy rate. The age of the donor, however, was directly related to the miscarriage rate. On the other hand, the age of patients undergoing IVF/GIFT was inversely related to the pregnancy rate and directly related to the miscarriage rate. In women of 40 years or over, the overall pregnancy and live birth rates were significantly higher and the miscarriage rate was significantly lower in the group receiving donated oocytes compared to the group using their own oocytes. In summary, we suggest that the age-related decline in fecundity is associated with the age of the oocytes rather than the age of the uterus.

Abortion, Spontaneous↗

Ethical and policy issues in altruistic living and cadaveric organ donation.

Organs for transplantation are usually obtained from living genetic relatives or from heart-beating cadavers. Unfortunately, these sources have so far been unable to keep up with demand. As a result, there is a large and steadily increasing number of potential recipients awaiting transplantation, some of whom will die before an organ can be found. In an attempt to rectify this tragic situation, several solutions have been proposed. This review will consider proposals designed to increase the availability of human organs without resorting to commercialism. These include expanding the use of living donors by: 1) encouraging donations by genetic relatives; 2) allowing volunteers a greater voice in determining their own suitability; 3) encouraging the use of emotionally related individuals and accepting altruistic strangers; and 4) considering motivated identical twin minors and older adolescents as donors. Suggestions for increasing the pool of cadaveric donors include: 1) overcoming the family consent barrier by presuming consent, mandating completion of binding advanced directives, or by eliminating the need for consent entirely; 2) reconsidering non-heart-beating donors; 3) elective ventilation for organ donation; and 4) accepting organs from anencephalic infants before brain death occurs. All of these proposals raise concerns which are discussed. Those approaches considered to be ethically acceptable and to hold promise for success should be vigorously pursued, beginning with carefully designed pilot studies. Hopefully, such an approach will eventually increase the number of organs available for patients suffering from end-stage organ disease.

Altruism↗

Experience with an organ procurement organization-based non-directed living kidney donation programme.

The organ procurement organization (OPO)-based non-directed living kidney donation programme was developed to decrease wait times for kidney transplants, and to meet the community's desire for altruistic living donation. Community awareness was encouraged through information about non-directed living kidney donation on the state donor registry Web site, and through the media. The OPO received all inquiries and responded with phone calls, e-mails, printed information, medical/social history questionnaires, interviews, and referrals to the transplant centres. Kidneys were allocated according to the United Network for Organ Sharing (UNOS) wait list for the evaluating transplant centre. Between March 2002 and 23 September 2005, there were 608 inquiries to the OPO about non-directed living kidney donation. In 41 months, 20 transplants occurred with kidneys from non-directed donors. The donor registry and OPO-sponsored publicity led to 578 of the 608 inquiries and 15 of the 20 transplants. OPO screening saved transplant centre resources by ruling out 523 inquiries, referring 76 to transplant centres for complete evaluations. Optional donor/recipient meetings appeared to be beneficial to those participating. OPO-based non-directed living donor programmes can be effective and efficient. Standardization of evaluation, allocation, and follow-up will allow for better data collection and more widespread implementation.

Adult↗

[Coordination and donation].

The progressive incorporation of organ transplants as a therapeutic resource resulted in organisational adaptation and overall transplant management, leading to the emergence of the figure of the transplant coordinator in the mid-1980s. In Spain, the National Organisation of Transplants (Organización Nacional de Transplantes - ONT) was created, establishing a system - called the "Spanish model" - based on a network of coordinators at three levels: national, the autonomous community and the hospital. This organisational structure is a point of reference at the world level. The prevalence of the Intensive Medicine specialisation amongst hospital transplant coordinators is remarkable. The majority of organs proceed from brain-dead patients with beating hearts and this requires the infrastructure offered by intensive care units. The functions of the coordinator can be summarised in guaranteeing a synchrony of all the elements and teams that come together in an organisational chain that has come to be called the "process of donation". Schematically, the crucial points that the hospital coordinator develops are the following: - Detection of the potential donor. - Maintenance of the donor. - Diagnosis of brain death. - Family consent. - Preparation of the hospital logistics. - Helping the relatives. - Direct involvement in the Program of Guarantee of Quality. - Person of reference in any activity related to the transplant. It would be desirable to achieve the creation of transplant coordination teams, with univocal messages, professionalism and a permanent input of the so-called "human factor", which is so necessary and also so close to the transplant world.

Brain Death↗

Clinical results from transplanting incompatible live kidney donor/recipient pairs using kidney paired donation.

CONTEXT: First proposed 2 decades ago, live kidney paired donation (KPD) was considered a promising new approach to addressing the shortage of organs for transplantation. Ethical, administrative, and logistical barriers initially proved formidable and prevented the implementation of KPD programs in the United States. OBJECTIVE: To determine the feasibility and effectiveness of KPD for the management of patients with incompatible donors. DESIGN, SETTING, AND PATIENTS: Prospective series of paired donations matched and transplanted from a pool of blood type or crossmatch incompatible donors and recipients with end-stage renal disease (6 conventional and 4 unconventional KPD transplants) at a US tertiary referral center (between June 2001 and November 2004) with expertise in performing transplants in patients with high immunologic risk. INTERVENTION: Kidney paired donation and live donor renal transplantation. MAIN OUTCOME MEASURES: Patient survival, graft survival, serum creatinine levels, rejection episodes. RESULTS: A total of 22 patients received transplants through 10 paired donations including 2 triple exchanges at Johns Hopkins Hospital. At a median follow-up of 13 months (range, 1-42 months), the patient survival rate was 100% and the graft survival rate was 95.5%. Twenty-one of the 22 patients have functioning grafts with a median 6-month serum creatinine level of 1.2 mg/dL (range, 0.8-1.8 mg/dL) (106.1 micromol/L [range, 70.7-159.1 micromol/L]). There were no instances of antibody-mediated rejection despite the inclusion of 5 patients who were highly sensitized to HLA antigens due to previous exposure to foreign tissue. Four patients developed acute cellular rejection (18%). CONCLUSIONS: This series of patients who received transplants from a single-center KPD pool provides evidence that recipients with incompatible live donors, even those with rare blood type combinations or high degrees of HLA antigen sensitization, can receive transplants through KPD with graft survival rates that appear to be equivalent to directed, compatible live donor transplants. If these results can be generalized, broader availability of KPD to the estimated 6000 patients with incompatible donors could result in a large expansion of the donor pool.

Adolescent↗

Professions, families, and control in the management of the cadaver organ donor.

In times of medical crisis, control over the treatment process is vested with the patient's attending physician. The role of the other members of the treatment team is clearly supporting of the physician while the patient's family exercises little or no influence over the treatment process. In certain "rare" events, the traditional roles are suspended and control of the process is, at lest temporarily, shifted to an outside group of health professionals. The process of cadaver organ donor donation is presented as an example of the suspension of traditional role responsibilities and the delegation of control to an external agent. Through direct observation of role interaction, in-depth interviews with medical personnel and a survey of critical care nurses, this process of shift in control is examined. Although the issues of time and the locus of control serve to constrain this process, the decision to accept or decline the request for organ donation ultimately lies with the patient's family. Under these rare circumstances, the family is asked to suspend their beliefs regarding life and death in favor of a new set of norms introduced by this external agent.

Behavioral Research↗

Study of asymptomatic microscopic hematuria in potential living related kidney donors.

Thirty potential living related kidney donors with asymptomatic microscopic hematuria of nonsurgical causes were entered in this study. They underwent thorough history taking, medical and ENT examination, laboratory and radiologic assessment and pure-tone audiometry. Family members were also subjected to urine analysis and audiometry. Moreover, the 30 donors were subjected to kidney biopsies which were examined by light microscopy, direct and indirect immunofluorescent microscopy, and electron microscopy. Hereditary nephritis (with or without sensorineural deafness) was found to be the most common cause of asymptomatic microscopic hematuria (25/30), followed by isolated C3 deposits disease (3/30), IgA nephropathy (1/30) and IgM nephropathy (1/30). Since these disease conditions are of a progressive nature, we have concluded that relatives of uremic patients with asymptomatic microscopic hematuria should not be considered for kidney donation even if they are strongly motivated.

Adult↗