Emerging models for facilitating contact between people genetically related through donor conception: a preliminary analysis and discussion.

Previous research indicates interest among some donor-conceived people, donors and recipient parents in having contact. Outcomes of such contact appear largely, but not universally, positive. This paper seeks to understand better the characteristics of associated support services. Information gathered using the authors' direct experiences and professional and personal networks in different parts of the world indicates the emergence of four main groupings: (i) publically funded services outside of treatment centers; (ii) services provided by fertility treatment or gamete bank services; (iii) services provided privately by independent psychosocial or legal practitioners; and (4) services organized by offspring and/or recipient parents. Key operational features examined were: (i) who can access such services and when; (ii) what professional standards and funding are in place to provide them; and (iii) how 'matching' and contact processes are managed. Differences appear influenced variously by the needs of those directly affected, local policies, national legislation and the interests of the fertility services which recruit gamete donors and/or deliver donor conception treatments. The paper is intended to inform fuller debate about how best to meet the needs of those seeking information and contact, the implications for the way that fertility treatment and gametes donation services are currently provided and future research needs.

Histological assessment of preimplantation biopsies may improve selection of kidneys from old donors after cardiac death.

Kidneys from old donors after cardiac death (DCD) may increase the donor pool but the prognosis of these kidneys is unsatisfactory. To improve these results, we retrospectively evaluated the diagnostic utility of published selection algorithms for old donor kidneys. We studied all DCD kidney transplantations between January 1, 1994 and July 1, 2005 at our institution (n = 199). Selection algorithms were evaluated in the subset of kidney transplantations from donors aged 60 years or older (n = 52). For histological assessment of kidney biopsies, glomerulosclerosis, tubular atrophy, interstitial fibrosis and vascular narrowing were blindly scored. Functional kidney weight was calculated as renal mass multiplied by the fraction of nonsclerosed glomeruli. Graft function and survival of kidneys from DCD aged 60 years or older were inferior to those from younger DCD. Histological scores were associated with kidney function and graft survival of old DCD kidney transplantations. Functional kidney weight was associated with kidney function but not graft survival, while donor glomerular filtration rate (GFR), donor age and machine perfusion characteristics were associated with neither of the clinical outcomes of interest. We conclude that histological assessment of preimplantation biopsies may improve the selection of kidneys from old DCD and may therefore contribute to expansion of the donor pool.

Differences in cortisol response affect the distinction of observed reactive and proactive aggression in children with aggressive behaviour disorders.

Various researchers distinguished two categories of aggressive behaviour, namely reactive and proactive aggression. Reactive aggression is an aggressive response to a perceived threat or provocation, whereas proactive aggression is behaviour that anticipates a reward. In the present study, including both a sample of disruptive behaviour disordered (DBD) and normal control (NC) children, we observed reactive and proactive aggressive behaviour during an experimental dyadic play session. DBD children showed more observed reactive and proactive aggression. Subsequently, we investigated whether the observed measures correlated with parent-rated measures of reactive and proactive aggression in. We distinguished in both NC and DBD children a subgroup showing a rise in cortisol level, i.e. responders, and a subgroup who did not show a rise in cortisol, i.e. non-responders. Results suggest that differences in the cortisol response affects the correspondence between observed and parent-rated reactive and proactive aggression since only DBD non-responders showed the expected correlations.

Recipient hemodynamics during non-heart-beating donor kidney transplantation are major predictors of primary nonfunction.

Non-heart-beating donor (NHBD) kidneys may substantially expand the donor pool, but many transplant centers are reluctant to use these kidneys because of the relatively high incidence of primary nonfunction (PNF). In heart-beating donor kidneys, intravascular fluid depletion during transplant surgery is associated with delayed graft function (DGF). Therefore, we studied the effect of the recipients' hemodynamic status on the outcome of 177 NHBD kidney transplantations. Independent statistically significant predictors of PNF were average central venous pressure (CVP) below 6 cmH(2)O (adjusted odds ratio (AOR) 3.1 (95% CI: 1.4-7.1), p=0.007), average systolic blood pressure below 110 mmHg (AOR 2.6 (95% CI: 1.1-5.9), p=0.03) and pre-operative diastolic blood pressure below 80 mmHg (AOR 2.4 (95% CI: 1.0-5.9), p=0.05). Donor characteristics were not independently associated with PNF (p>0.10). In a subgroup analysis of 56 paired kidneys, 29% of the recipients with the lower CVP of the pair experienced PNF compared with 11% of their counterparts with higher CVP (p=0.09). Our study indicates that recipient hemodynamics during transplant surgery are major predictors of PNF. Therefore, improving recipient hemodynamics by expansion of the intravascular volume is expected to enhance the results of NHBD kidney transplantations and may enlarge the donor pool by increasing the acceptance of NHBD kidneys.

Therapeutic drug monitoring of tacrolimus with the dried blood spot method.

In a preliminary investigation an assay for tacrolimus based on fingerprick sampling and consecutive application as a blood spot on sampling paper has been developed. The dried blood spot was analysed by HPLC-tandem mass spectrometry. The validated range was 1-30 microg/l. Intra- and inter-assay variability for precision and accuracy was <7.5% and 15%, respectively. Tacrolimus concentrations of 24 stable out patients were compared after both blood spot sampling and conventional venous sampling. Method agreement was investigated with the methods of Passing and Bablok and Bland Altman and proved suitable for clinical use. The dried blood spot method for tacrolimus seems promising for patient monitoring.

Preservation of renal function and cardiovascular risk factors.

An update is given about some factors leading to loss of renal allograft, especially in relation to the use of tacrolimus and cyclosporine. We discuss both immunological, such as suboptimal immunosuppression, acute rejection, and noncompliance, as well as nonimmunological factor's such as hypertension, hyperlipidemia, chronic toxic effects of immunosuppressants, older donors, and delayed graft function.

Kidney transplantation using elderly non-heart-beating donors: a single-center experience.

Although acceptable outcomes have been reported in both non-heart-beating (NHB) and elderly donors individually, the large pool of elderly NHB donors has not yet been fully utilized. In 1994, we expanded our transplant protocol to include NHB donors aged over 65 years and this study compares the clinical outcomes with regular NHB transplantations. Up to June 2005, 24 patients were transplanted at our center with kidneys from NHB donors aged 65 years or more, whereas 176 patients received grafts from conventional NHB donors during the same period. Grafts from older donors were associated with inferior glomerular filtration rates (29 vs. 44 mL/min after 1 year, p=0.01) and graft survival (52% vs. 68% after 5 years, p=0.19) compared to younger NHB donor grafts, although the difference in graft survival was not statistically significant. Exclusion of older NHB donor kidneys with severe vascular pathology resulted in similar graft survival of older and younger NHB donor kidneys. We conclude that the use of elderly NHB donors in order to expand the donor pool was associated with unacceptable clinical outcomes and cannot be justified without further refinement in their selection, for example, by histological assessment of pretransplant biopsies.

The impact of an organ donation registration information program for high school students in the Netherlands.

In 1998, a new organ donor registration system was implemented in the Netherlands to increase the number of potential donors. A high school education program was developed to prepare adolescents to make an informed decision about organ donation. A post-test only randomised controlled trial was conducted in 39 high schools including 2868 students. Students within schools were randomly allocated to either attend the organ donation education program or not. The impact of the program on students' intention to register their organ donation preference (and determinants thereof) were analysed using multivariate multileveling modelling (MlwiN). The results show that students who were exposed to the education program had more favourable registration intentions (B = .40), were more often willing to be donors (OR = 1.45), and had greater knowledge about (B = 3.84) and more positive social outcome expectations (B = .09) and self-efficacy regarding organ donation registration (B=.22). Lastly, they experienced significantly less negative outcome expectations related to organ donation registration (B = -.15). Students' evaluation of the school-based education program was favourable. The present organ donation registration program proved to be effective in changing determinants of organ donation registration, and a large-scale implementation in the Dutch high school curriculum is planned.

Life history of wild Sumatran orangutans (Pongo abelii).

We present life history data on wild Sumatran orangutans gleaned from a 32-year and a 5.5-year study. Estimated age at first reproduction was 15.4 years. At 9.3 years, the average interbirth interval for this population is the longest ever recorded for any great ape population, significantly longer than that of a Bornean orangutan population. We find that age-specific mortality of Sumatran orangutans does not differ between sexes and is significantly lower than that of wild chimpanzees. We conclude that orangutan life history is the slowest among extant great apes. In accordance with their slow life history, longevity in the wild is estimated to be at least 58 years for males and at least 53 for females. We find no evidence for menopause. These data suggest that compared to the ancestral state, humans have undergone less of an increase in longevity than commonly assumed, and have experienced selection on earlier cessation of reproduction.

Process evaluation of a school-based education program about organ donation and registration, and the intention for continuance.

This paper describes the process evaluation of an organ donation education program for high school students aged 15-18 years of which the effectiveness was established. The program consisted of three components: a video with group discussion, an interactive computer-tailored program and a registration training session. A cross-sectional survey was conducted among 50 teachers who had recently worked with the program. The results show that all teachers reported to have implemented at least two of the three intervention components, while a majority of teachers reported to have implemented all components. Teachers' attitudes toward the program were generally positive. They reported that the opinions of students and colleagues in their own department were most influential in their decision to provide the education program. Furthermore, teachers were very confident about their ability to apply the different parts of the education program. The educational quality of the program was evaluated as moderately positive and almost all teachers had the intention to use the program again in the future. Because of the positive evaluations and intentions for future implementation by teachers, and justified by its previously established effectiveness, the education program should be considered for large-scale dissemination among high schools in The Netherlands.

The impact and evaluation of two school-based interventions on intention to register an organ donation preference.

The present paper describes the impact and evaluation of two intervention components-a video with group discussion and an interactive computer-tailored program-in order to encourage adolescents to register their organ donation preference. Studies were conducted in school during regular school hours. The video with group discussion in class had a positive impact on the intention to register an organ donation preference as well as on the intention to register as a posthumous organ donor. The computer-tailored program had no surplus value when compared to reading an extensive brochure with general information on organ donation. However, participants appreciated the tailored information more than the brochure. It may be that having provided general information before exposure to the tailored program, the tailored intervention will be more effective. This needs to be tested in a further experiment.

Metabolic aspects of tacrolimus in renal transplantation. Consequences for the choice of an immunosuppressive regimen and for the management of post-transplant diabetes mellitus.

The occurrence of post-transplant diabetes mellitus (PTDM) is an important complication after renal transplantation associated with an increased risk of chronic transplant dysfunction and of cardiovascular morbidity and mortality. Both tacrolimus and cyclosporine have been associated with PTDM. In the initial studies, PTDM seemed to occur more often in tacrolimus treated patients than in cyclosporine treated patients. The mechanism by which tacrolimus could cause PTDM was unknown and the relative roles of tacrolimus and corticosteroids, which are often prescribed concomitantly with tacrolimus, were unknown. In several studies we used fasting glucose and insulin levels to assess (peripheral) insulin resistance, and intravenous glucose tolerance tests to assess insulin secretion by the pancreatic b-cells in response to a stimulus (glucose load). Thus, we evaluated the mechanism by which tacrolimus causes glucose metabolic disorders, risk factors for glucose metabolic disorders during tacrolimus treatment, the relative roles of corticosteroids and tacrolimus trough levels in glucose metabolic disorders, and also differences in glucose metabolism between patients using tacrolimus versus patients using cyclosporine. Based on the results of these studies and the available literature, the consequences for the choice of a primary immunosuppressive agent and guidelines for the treatment of PTDM during tacrolimus-based immunosuppression are discussed.