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PubMed2003

Awareness of eye donation in an adult population of southern India. A pilot study.

PURPOSE: To determine "awareness of eye donation" and corneal transplantation in an adult population of southern India. METHODS: 507 participants chosen by systematic random sampling were interviewed using a structured questionnaire. Participants were selected among patients attending two community outreach programmes at different sites, and from patients presenting directly to the hospital. RESULTS: 257 participants (50.69%) were aware of eye donations. The major source of awareness was publicity campaigns (n=105). Only 22 (4.34%) participants were aware that eye donation had to be done within 6 hours of death. Four hundred and three (79.50%) participants were not aware of corneal transplantation. Illiteracy and rural residence were more likely predictors of ignorance. CONCLUSION: Although multiple strategies are currently followed to increase awareness of eye donations and corneal transplants, more innovative strategies have to be developed, especially to target illiterate and rural populations.

Adult↗

PubMed1994

The polymerase chain reaction and hepatitis C virus diagnosis.

In the absence of tissue culture, electron microscopy or assays for viral antigen, the direct detection of hepatitis C virus (HCV) is by necessity dependent upon nucleic acid hybridisation methods. Of the available methods, amplification of HCV cDNA by polymerase chain reaction (PCR) commends itself by virtue of its extreme sensitivity and its consequent ability to detect the very low levels of HCV-RNA that are present in many clinical samples. In this review the development and evolution of PCR techniques for HCV detection are described and a number of clinical applications are considered in detail. The applications include diagnosis of acute infection during the seronegative window period prior to the appearance of HCV antibodies, and diagnosis of HCV infection in the immunosuppressed. PCR also enables identification of the chronic viraemic carrier state and it permits accurate monitoring of the antiviral effects of drugs such as interferon. Confirmation of the specificity of HCV antibody assays and detection of HCV contamination of blood donations and blood products are other important areas in which PCR techniques have proved invaluable. In addition, PCR-based techniques underlie an increasing number of molecular epidemiological and genotyping studies and they are providing insights into the details of HCV cellular tropism and replication. A number of logistic problems and operational difficulties are also discussed. Despite these limitations it is concluded that PCR will continue to make significant contributions to both clinical practice and to our understanding of the basic biology of HCV infection.

Blood Donors↗

PubMed2006

[Computer-assisted planning in living donor liver operation].

INTRODUCTION: The appropriate recipient/donor match is a prerequisite for successful living donor liver transplantation (LDLT). A precise knowledge of the liver anatomy and the functional liver volume plays a key role in allocating live liver donor candidates. With the new software HepaVision, we obtained information on liver mapping by means of virtual 3-dimensional non-invasive imaging reconstructions and were able to perform a virtual simulation of the liver transsection. Aim of our study was to investigate, whether this new computer technology is advantageous in surgery planning for LDLT. METHODS: From January 2002 until December 2004 355 liver transplantations were performed in our department, of which 36 were LDLT. According to our evaluation protocol 135 potential donors (63 male, 72 female) between 18 to 59 years received preoperatively an all-in-one CT. The acquired data sets were further analysed with the software HepaVision (MeVis, Germany). RESULTS: Of the 135 evaluated donors, we excluded 99 (73 %) from donation based on the HepaVision-data. Reason for exclusion was an inadequate liver volume (70.8 %) or a risk related anatomical anomaly (2.2 %). In the remaining 36 cases a successful graft donation was possible. There were no postoperative complications in the donors and recipients, directly related to a misjudgment of the anatomy or miscalculation of the liver volume. CONCLUSION: The systematic use of HepaVision for surgery planning proved to be indispensable for proper donor selection. A virtual simulation of the liver transsection on 3D-model additionally increased the safety of the operation, consequently decreasing the risk for the donor.

Adolescent↗

PubMed1993

Potentiation of NMDA receptor-mediated transmission in turtle cerebellar granule cells by activation of metabotropic glutamate receptors.

1. The effects of metabotropic glutamate receptor (mGluR) agonists on excitatory postsynaptic potentials (EPSPs) evoked by stimulation of mossy fibers (MF) and parallel fibers (PF) were examined in turtle cerebellar Purkinje cells. 2. The mGluR agonist 1S,3R-ACPD (1-25 microM) reversibly potentiated the amplitude of the MF-evoked EPSPs, but was without effect on PF-evoked EPSPs. The potentiation of MF-evoked EPSPs was dose-dependent, with a median effective dose (ED50) of approximately 4.4 microM. At higher doses (15-25 microM) 1S,3R-ACPD produced a direct depolarization of Purkinje cells in 58% of cells examined. 3. The enhancement of MF EPSPs by 1S,3R-ACPD was mimicked by 1S,3S-ACPD (50 microM) and blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonovalerate (D-AP5), but not by the mGluR antagonist L-2-amino-3-phosphonopionic acid (L-AP3; 1 mM), or the 1R,3S isomer of ACPD (25-500 microM). 4. Quisqualate (1 microM) produced a biphasic effect on MF EPSPs, producing an initial blockade of the EPSP followed by a D-AP5-sensitive potentiation. 5. The potentiation of MF EPSPs by 1S,3R-ACPD was not blocked by prior exposure to the protein kinase C activator phorbol 12-myristate 13-acetate (10 microM), the protein kinase C inhibitor calphostin C (1 microM), the adenylate cyclase activator forskolin (25 microM), or the nitric oxide donator sodium nitroprusside (1 mM). Preincubation of the tissue for 24-48 h in pertussis toxin also failed to prevent the ability of 1S,3R-ACPD to potentiate the NMDA receptor-mediated component of the MF EPSP. PF EPSPs were also not significantly affected by these agents. 6. The results demonstrate that the mGluR agonists 1S,3R-ACPD, 1S,3S-ACPD, and quisqualate produce a potent, stereospecific potentiation of NMDA receptor-mediated transmission at the MF-granule cell synapse. Agents that modulate the intracellular messengers protein kinase C, adenylate cyclase, nitric oxide, or pertussis toxin-sensitive G proteins failed to mimic or block this effect. This would suggest that the potentiation of NMDA receptor-mediated transmission at this synapse is not mediated via these systems, and reflects a different site of action of mGluR agonists on the NMDA receptor. The observed interaction between mGluR and NMDA receptors in granule cells provides a means for activity-dependent modulation of synaptic transmission, which may play a role in synaptic integration at the MF-granule cell synapse.

2-Amino-5-phosphonovalerate↗

PubMed2003

Financial considerations in living organ donation.

The shortage of cadaveric organs and increased success of living donor transplantation support the use of living organ donors. Clinical social workers have the opportunity to explore a variety of donor-specific issues when performing psychosocial evaluations of living donors, including motivation, psychological stability, and personal and family consequences of donation, as well as the direct and indirect financial consequences faced by living donors. Although most donor-related medical costs are covered, other associated expenses are not reimbursable and may put donors at risk for financial hardship. Out-of-pocket expenses also serve as a disincentive to donate for some volunteers. During the evaluation process, healthcare professionals should openly discuss how surgery, recovery, and any potential complications might impact prospective donors' financial situation. Donors can then decide whether they are able to realistically handle the costs of donation. We present the financial dilemmas experienced by many living donors and highlight efforts that have been made to deal with them.

Absenteeism↗

PubMed1998

Erectile dysfunction in aging: upregulation of endothelial nitric oxide synthase.

OBJECTIVES: To evaluate whether alterations in nitric oxide (NO) synthesis or activity contribute to age-related erectile dysfunction and to elucidate the mechanisms causing these alterations using the rabbit as our model of aging. METHODS: We compared the ability of the rabbit cavernosal smooth muscle to relax in the organ bath in response to acetylcholine (Ach, endothelium-dependent vasodilator), sodium nitroprusside (SNP, an NO donor), and A23187 (a calcium ionophore) in young (6 month old) and aged (2.5 to 3.5 year old) rabbits. In addition, the immunohistochemical expression of endothelial nitric oxide synthase (eNOS) in both young and aged rabbit cavernosal tissue was examined. Endothelial integrity was examined immunohistochemically with JC70. RESULTS: Ach-mediated relaxation of penile corporal tissue was significantly attenuated from a maximum of 68.39 +/- 6.27 (0.1 mM Ach, n = 4) in young rabbits to 39.02 +/- 4.88 (0.1 mM Ach, n = 6) in aged rabbits (P < 0.04). No statistically significant difference (P > 0.05) was noted between cavernosal relaxation to sodium nitroprusside between young rabbits (97.8%, 0.1 mM SNP, n = 5) and aged rabbits (76.1%, 0.1 mM SNP, n = 5). This suggested that the defect in the Ach-NO pathway was at the level of NO synthesis, not activity. Immunohistochemical staining for eNOS demonstrated upregulation in both the vascular endothelium and corporal smooth muscle of aged rabbit tissue compared with young rabbit cavernosal tissue (n = 5). Anatomic endothelial integrity was demonstrated in the young and aged rabbits by the presence of JC70. This suggested that the defect in the Ach-NO synthetic pathway was not at the level of eNOS and was not due to anatomic endothelial cell disruption. Finally, Ach-mediated cavernosal smooth muscle relaxation in the young rabbit was not significantly augmented (P > 0.05) in the presence of the calcium ionophore A23187 (10 microM). A23187, however, significantly augmented (P < 0.04) Ach-mediated relaxation in the aged rabbit from a maximum of 33.93 +/- 6.58 to 41.55 +/- 6.58 (10 microM Ach, n = 5). This suggested that a potential defect in the Ach-NO synthetic pathway was at the level of intracellular calcium flux and possibly at the level of the calcium-eNOS interaction. CONCLUSIONS: Endothelium-dependent relaxation is attenuated in the aging rabbit; eNOS is upregulated in the aging rabbit; and no difference is noted in response to direct NO donation between the young and aged rabbit. The endothelium is anatomically intact in both the young and aging rabbit. The calcium ionophore A23187 augmented the attenuated vasorelaxation in the aging rabbit cavernosum (although not to the levels seen in the young rabbit cavernosum) and had no effect on the young rabbit cavernosum. These data suggest that erectile dysfunction in the aging rabbit cavernosum appears to be related to endothelial dysfunction and is characterized by eNOS upregulation and aberrant intracellular calcium fluxes.

Acetylcholine↗

PubMed1985

Endothelial cell densities in corneal donor material.

The mean endothelial cell count of 282 donated corneas was 2,665 cells/mm2, and the mean donor age was 56.01 years. The majority of the donors were over the age of 40 years, and the major causes of death were malignancies and myocardial infarction. Vital staining of the endothelium and direct evaluation of cells with an inverted phase contrast microscope were used in assessing the viability of this monocell layer. Evaluation of endothelial photomicrographs revealed that the cell count falls in the first three decades of life and eventually stabilizes around 2,600 cells/mm2. It is therefore suggested that patient age should not be the primary criterion for donor corneal selection.

Adult↗

PubMed1989

Establishment of a nonanonymous donor oocyte program: preliminary experience at the University of Southern California.

Transvaginal ultrasound-directed oocyte retrieval was performed on eight women functioning exclusively as gamete donors for 10 patients with ovarian failure. Donors included sisters, personal friends, and compensated participants selected by the recipient couple. Oocyte donors underwent controlled ovarian hyperstimulation and transvaginal oocyte aspiration. Thirteen initiated cycles resulted in 11 embryo transfers and six ongoing pregnancies. There were no complications, and all donors stated a willingness to undergo the procedure again. The use of nonanonymous oocyte donation appears both efficacious and efficient and is recommended as an option for achieving pregnancy in women with ovarian failure.

Adult↗

PubMed1989

Herpes simplex virus neurovirulence and productive infection of neural cells is associated with a function which maps between 0.82 and 0.832 map units on the HSV genome.

A herpes simplex virus (HSV) intertypic recombinant (RE6) has been shown to be completely and specifically non-neurovirulent in mice. Direct intracranial inoculation of 10(8) PFU of RE6 does not result in a lethal encephalitis. Neurovirulent recombinant viruses were generated by cotransfection of RE6 DNA with DNA fragments cloned from the pathogenic HSV-1 strain 17 syn+. It was found that a 1.6-kb fragment mapping between 0.82-0.832 m.u. could restore the neurovirulent phenotype. Recombinants which incorporated at least part of this fragment were at least 100,000-fold more neurovirulent than RE6. The recombinants displayed a greatly enhanced capacity to replicate in mouse brain in vivo, but did not display enhanced replication over that of RE6 in cultured mouse cells at 38.5 degrees. Immunohistochemical analysis of infected mouse brain tissue revealed that the permissive host cell range of the recombinants was dramatically altered from that of RE6. While antigen positive cells were extremely rare in mouse brain tissue infected with RE6, the neurovirulent recombinants produced antigens in many cell types including neurons. Thus, wild-type HSV-1 sequences mapping between 0.82-0.832 m.u. can donate a highly neurovirulent phenotype to RE6.

Animals↗

PubMed2005

Metal compartmentation and speciation in a soil sentinel: the earthworm, Dendrodrilus rubidus.

Earthworms are well-studied organisms in ecotoxicology because of their keystone ecological status and metal-accumulating capacity. However, the direct estimation of the bioreactive fractions of accumulated metal burdens remains technically elusive. In this study we exploited two physical techniques, electron probe X-ray microanalysis (EPXMA) and X-ray absorption spectroscopy (XAS), to improve understanding of the subcellular spatial distributions, ligand affinities, and coordination chemistries of Cd, Pb and Zn in a field population of the epigeic earthworm, Dendrodrilus rubidus. EPXMA and XAS analyses were performed on cryopreparations to maintain compositional fidelity; EPXMA data were analyzed by multivariate statistics. XAS provided whole-worm insights; EPXMA provided in situ, subcellular data from the major metal-sequestering tissue, the chloragog. Both techniques showed that Cd is coordinated with S; the measured Cd-S bond distance in XAS suggests a metallothionein-type ligand. The mean Cd:S molar ratio (EPXMA) of 0.36 is higher than the ratio of 0.29 estimated from published biochemical data. EPXMA and XAS data also found that Ca, Pb, and Zn are predominantly bound to one or more O-donating, probably phosphate-rich, ligands. X-ray distribution maps (EPXMA) of the hepatocyte-resembling chloragocytes revealed that the O-seeking (Ca, Pb, Zn) metals and S-seeking Cd bioaccumulate in distinct organelles. Extended X-ray absorption fine structure showed that the Pb complex is not biogenic pyromorphite, although X-ray absorption near edge structure did not eliminate the possibility. XAS provided no evidence of Pb spillage from the "sequestration compartment" within D. rubidus. However, the correspondence of Pb with Ca and P in EPXMA is not as strong as that of Zn. This is indicative either of spillover or of a second, hitherto unidentified, sequestered-Pb pool. By exploiting the complimentary techniques of EPXMA and XAS,we are closer to describing the mechanistic link between equilibrated body burdens and biomarker responses in earthworms.

Animals↗

PubMed2004

Donor and nondonor families' accounts of communication and relations with healthcare professionals.

The cadaveric organ procurement scheme in the United Kingdom is based on a voluntary, opt-in system. However, regardless of whether and how individuals make their wishes known about organ donation before death, health professionals are required to seek the families' "lack of objection" before organ removal. Relationships between families and healthcare professionals have been identified as important regarding patients who receive mechanical ventilation, familial understanding of brain stem death, organ donation requests, and postoperative care. This qualitative study was conducted over a 2-year period in Scotland. Semistructured interviews with donor (n=19) and nondonor families (n=4) explored their accounts of communication and interaction with healthcare professionals. The data suggest strategies that can support relatives, including early direct and tacit communication regarding recovery prospects, provision of clear and timely information about brain death, assurances regarding respectful treatment of the decedent's body, wearing nonsurgical attire, and follow-up care, if needed.

Adolescent↗

PubMed1991

Oocyte and pre-embryo donation to women with ovarian failure: an extended clinical trial.

The outcome of a series of pre-embryo transfers to 31 women with ovarian failure is described. Twenty six fertile women functioned as nonanonymous donors, providing oocytes for in vitro fertilization after undergoing controlled ovarian hyperstimulation and transvaginal ultrasound directed oocyte aspiration. Recipients, 24 to 44 years of age, received hormone replacement therapy before pre-embryo transfer (ET). A mean of 13.7 +/- 1.1 oocytes were obtained per aspiration resulting in the transfer of 4.5 +/- 0.2 pre-embryos to each recipient couple. Twenty-five of 47 ET resulted in pregnancy (53.2% per ET); 5 preclinical, and 20 clinical, of which 18 are ongoing or delivered. The overall implantation rate per individual transferred fresh pre-embryo was 21.1%. We conclude that oocyte donation is a safe and highly efficient means of achieving pregnancy for women with ovarian failure.

Adult↗

PubMed1988

Anonymous and non-anonymous oocyte donation preliminary results.

During the past year, we have developed an oocyte donation programme in 10 patients with complete absence of endogenous ovarian function (premature ovarian failure in seven cases, castration in two cases and Turner's syndrome in one case). In cases of anonymous donation, donors were volunteers devoid of any major genetical risk who were included in our IVF programme and who consented to donate one oocyte when at least seven oocytes were recovered, and two oocytes when at least 11 oocytes were recovered, to a recipient couple. As far as possible, morphological characteristics of both couples were paired. In cases of non-anonymous donation, donors were 'affective' donors, having at least one child. The resulting embryos after IVF of donated oocytes were either replaced directly in recipient women which required synchronization of the donor's and recipient's cycles, or cryopreserved and then thawed, usually at day 16 of recipient's artificial cycle, i.e. 2 days after introduction of the progestational compound. On the 10 patients entering this oocyte donation programme (20 cycles), 13 transfers were carried out resulting in four clinical pregnancies in three patients with premature ovarian failure and one with Turner's syndrome (20% pregnancy per cycle and 31% per transfer). Despite the small numbers, these good results prompted us to develop this protocol.

Adult↗

PubMed2004

[Cross-over transplantation; a new national program for living kidney donations].

In the Netherlands, cross-over kidney transplantation has been introduced as an extra option in the living kidney donation programme. In cross-over transplantation, patients who cannot be given their own partner's kidney for immunological reasons are given a kidney from the partner of another patient in exchange for a kidney from their own partner. There is no difference in the medical indications and contraindications between direct and indirect living donation. There are no ethical obstacles since the net gain for the two couples is no different from that of direct living kidney donation and because the exchange takes place on the basis of equality. One should be aware that the extra possibilities may result in more psychological pressure on potential donors. It is important that the donation procedures start at the same moment and that the wishes of patients and donors for anonymity be preserved. A successful cross-over kidney transplantation programme requires a large pool of donors and patients. Therefore, this has been organised in a national programme. The Dutch Transplantation Foundation is responsible for the allocation of cross-over kidneys. Organ trade will thus be impossible. The seven Dutch centres for kidney transplantation have developed a protocol.

Female↗

PubMed2003

The experiences of donor families in the hospice.

OBJECTIVES: This study explored the experiences, attitudes and feelings of relatives who consented to donation of corneas of a loved one who had died of cancer. DESIGN: Semi-structured interviews were conducted by a single researcher and qualitatively analysed for systematic identification of themes. SETTING AND PARTICIPANTS: Two specialist palliative care units in Southern England participated. The names of donor families were obtained via transplant coordinators, the local eye bank and hospice records. Ten donor families were interviewed, four to 12 months after their relative's death. RESULTS: The majority of interviewees had thought the deceased was ineligible for donation due to cancer or old age. Approaches regarding donation were generally made by nurses and described as sensitive by relatives. Very few family members would otherwise have considered or raised the subject. Almost all were glad they had agreed to donation although few felt it directly affected their bereavement. A range of motivations for consent was encountered but decisions were very much easier if the deceased's wishes were already known. Most favoured an opt-out system or the right of the family to decide if the deceased's wishes were not known. CONCLUSIONS: Corneal donation is possible for patients dying from cancer. This study indicates that it is generally regarded positively by donor family members. Education of the public and health professionals is necessary to highlight both the eligibility criteria and the need for donation. Families should be encouraged to discuss donation to facilitate respecting individuals' wishes. In the absence of a known decision from the deceased, health professionals should be aware of their responsibility to discuss the issue with the family.

Attitude of Health Personnel↗

PubMed2003

Cost-benefit approach in evaluating investment into donor action: the German case.

Donor Action (DA) is an international initiative to help critical care units (CCUs) increase their own donation rates through improved-quality donation practices. Following a validated diagnostic review (DR), areas of weakness can be identified, and the appropriate changes introduced. Data gathered from a number of centers in nine European countries (including Germany) 1 year after the introduction of targeted improvement measures demonstrated a 59.2% (P=0.0015) increase in donation rates. This analysis computes the cost-benefit thresholds of implementing the DA methodology from a German health-economic point of view, taking into account the treatment alternatives for end-stage renal disease (dialysis and transplantation) and comparing the DA program with current organ-donation practice. Lifetime direct medical costs and quality-adjusted life years (QALYs) were calculated for both arms, considering only changes in cadaveric renal transplantation rates. If DA leads to a 59% overall increase in organ donation in Germany, the program will result in 33 QALYs and 1.8-million euro cost savings per million population (PMP). Therefore, DA would be cost-effective below 2.66-million euro implementation cost PMP (or 218-million euro for the whole country). As the partial implementation cost of the program was far below the threshold, DA is more cost-effective than other publicly reimbursed medical intervention.

Cost Savings↗

PubMed2002

[Gasless laparoscopy-assisted live donor nephrectomy].

PURPOSE: We evaluated both efficacy and feasibility of laparoscopy-assisted live donor nephrectomy. MATERIALS AND METHODS: Since September 2000, 11 living kidney donors (2 males and 9 females) underwent laparoscopy-assisted live donor nephrectomy. All of sides were left. Gasless surgery was performed with a 7 cm pararectal upper abdominal incision and three trocars via a retroperitoneal approach. After creating the working space using balloon dissection technique, the abdominal wall was lifted using a metal retractor attached to the margin of the abdominal incision. Additionally, a metal plate, which was attached to the abdominal wall inside, was raised. The surgeon dissected left kidney from the skin incision under both direct vision and magnificated view on the monitor. RESULTS: The operating time, estimated blood loss and warm ischemic time were a mean of 209 minutes, 219 g, and 4.2 minutes, respectively. The mean times for the return to a normal diet and unassisted ambulation were 1.3 and 1.8 days, respectively. One case required blood transfusion due to subcutaneous hematoma at trocar entry site on the second day after surgery, in the remaining 10 cases there were no complications. All of donated kidneys achieved immediate function after engraftment. CONCLUSIONS: Gasless laparoscopy-assisted donor nephrectomy is recommended and advantageous for healthy kidney donors as a minimally invasive method.

Adult↗

PubMed2004

Ethical dilemmas in the treatment of children with disabilities.

Issues relating to the treatment of children with disabilities, such as withholding treatment, organ donation, research, genetic screening, and prenatal diagnosis, all present ethical dilemmas. These issues always need to be reviewed to determine which ethical considerations apply. Identifying relevant principles, one can conclude which take precedence and what is ethically permissible. As with so many other medical responsibilities, this can be consulted, learned, practiced and improved upon. Pediatricians caring for children with disabilities can study and enhance their capacity for ethical reflection, so as to participate fully in these important decision-making processes.

Abortion, Induced↗