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Donor selection in living-donor lung transplantation for familial pulmonary fibrosis: A narrative review and single-center practical approach.

In Japan, living-donor lobar lung transplantation (LDLLT) remains an important therapeutic option because of the persistent shortage of brain-dead donors. Interstitial lung diseases (ILDs) are a major indication for transplantation; however, the use of biologically related donors raises concerns regarding shared genetic susceptibility. Approximately 20% of ILD patients have a family history of ILD, referred to as familial pulmonary fibrosis (FPF). FPF is defined as fibrotic ILD occurring in at least two first- or second-degree relatives and is associated with poor prognosis regardless of the presence of identifiable genetic variants. Furthermore, interstitial lung abnormalities have been reported in 14-22% of first-degree relatives of patients with FPF, suggesting a substantial latent risk of disease development both in donors and recipients. These findings have important implications for donor selection in LDLLT. At Kyoto University Hospital, first-degree relatives from affected lineages are generally excluded as donor candidates, whereas relatives from unaffected family branches may be considered after careful individual assessment. Even in cases without a family history, biologically related donor candidates should be adequately informed of the potential future risk of ILD. Future directions include the incorporation of genetic testing and telomere length assessment and the establishment of prospective cohorts to enable risk stratification and long-term outcome evaluation. In conclusion, the selection of donors for LDLLT in patients with FPF requires a cautious and individualized approach that integrates family history, clinical evaluation, and genetic information to balance donor safety with access to transplantation.

Humans

CanDo (Canadian Donor Milk) randomised controlled trial: pasteurised human donor milk supplementation in the well-baby unit - protocol.

INTRODUCTION: Mother's milk is the gold standard for feeding newborns. Despite lactation support while in hospital, supplementation rates remain high in Canadian well-baby units at 35-50%. When supplementation is needed, the choice between formula milk and pasteurised human donor milk (donor milk) remains uncertain with a lack of clinical trials to inform this practice. This study aims to compare the effect of supplementing mother's milk with donor milk versus formula in infants at higher risk for supplementation (infants of diabetic mothers, infants born small for gestational age or with a birth weight less than 2.5 kg and late preterm infants born between 350/7 and 366/7 weeks gestation). METHODS AND ANALYSIS: This is an ongoing, open-label, single-centre, randomised controlled trial conducted at Mount Sinai Hospital, Toronto, Canada. A total of 112 infants (56 per group) will be randomised to receive donor milk or infant formula as a supplement to mother's milk during their initial hospital stay, when supplementation is deemed necessary by the family and/or healthcare team. The primary outcome is exclusive human milk feeding at 4 months of age. Secondary outcomes include any or exclusive human milk feeding at 1, 2 and 3 months; infant growth and health indicators and breastfeeding self-efficacy. Exploratory outcomes encompass infant temperament; parental mental health (assessed using the State-Trait Anxiety Inventory and Edinburgh Postnatal Depression Scale); milk cortisol concentrations; and informal milk sharing comparing donor milk and formula supplementation. Follow-up includes monthly telephone assessments and a virtual or in-person visit at 4 months post partum. Data will be analysed using intention-to-treat principles. ETHICS AND DISSEMINATION: The CanDo trial has received ethics approval from the Mount Sinai Hospital Research Ethics Board and the University of Toronto. Results will be disseminated through peer-reviewed journals, conference presentations and stakeholder engagement with hospital and public health decision-makers. Findings will address a critical evidence gap regarding the use of donor milk supplementation in well-baby units and may inform future clinical practice and policy in newborn feeding. TRIAL REGISTRATION NUMBER: NCT06315127.

Humans

Analysis of HLA Allelic and Haplotypic Frequencies in a Cohort of Bone Marrow Donors in Catalonia: Impact of Next-Generation Sequencing on Donor Registry Quality.

In haematopoietic stem cell transplantation (HSCT), the volunteer unrelated donor (VUD) has become the most common strategy in Europe, as improved outcomes are achieved through HLA compatibility at allelic-level resolution. In this context, the implementation of next-generation sequencing (NGS) in histocompatibility typing laboratories has significantly enhanced the quality of bone marrow registries, enabling a high level of resolution at a lower cost and improved performance. In this study, we analyse a large cohort of 21,787 bone marrow donors in Catalonia and present the observed HLA allelic and haplotypic frequencies, along with their linkage disequilibria. HLA-A, -B, -C, -E and -G were genotyped at full resolution, while -DRB1, -DQB1, -DQA1, -DPA1 and -DPB1 were genotyped at high resolution. We identified 236 new officially named HLA alleles, both coding and non-coding regions. This study highlights that the implementation of high-throughput HLA typing has led to an increase in the number of registered donors and an improvement in quality, which has been reflected in a rise in the number of effective donors.

Humans

Role of the H-2 complex in induction of T helper cells in vivo. I. Antigen-specific selection of donor T cells to sheep erythrocytes in irradiated mice dependent upon sharing of H-2 determinants between donor and host.

When purified CBA lymph node T cells were mixed with sheep erythrocytes (SRC) and filtered from blood to lymph through irradiated syngeneic mice for 1-2 days, the donor cells lost their capacity to stimulate anti-SRC responses by CBA B cells; the response to a third-party antigen (horse erythrocytes) was unaffected and active suppression was not involved. This process of specific negative selection to SRC also occurred when semiallogeneic mice were used as filtration hosts. By contrast, when allogeneic hosts were used the helper function of the donor cells was not reduced; this applied to both primed and unprimed T cells. Studied with congeneic resistant strains indicated that negative selection to SRC occurred only when the donor and host shared H-2 determinants. Studies with T cells depleted of alloreactive lymphocytes showed that negative selection to SRC in irradiated F1 hybrid mice was followed by a stage of positive selection where the donor cells gave greatly increased responses to the injected antigen. Positive selection did not occur in H-2-different mice, however, and the helper function of the donor cells remained unchanged. By these parameters it was concluded that homozygous T helper cells have no detectable capacity to recognize antigen in an H-2-different environment.

Animals

DL-ethionine treatment of adult pancreatic donors. Amelioration of diabetes in multiple recipients withe tissue from a single donor.

Transplantation of adult rat pancreatic islet tissue as a free graft requires the separation of islet from exocrine tissue to avoid host injury or graft destruction by digestive enzymes. The poor yield from islet isolation techniques currently necessitates the use of multiple donors to ameliorate diabetes in a single recipient. DL-ethionine (DLE) is an agent selectively toxic to the exocrine pancreas. We examined the effect of DLE administration on pancreatic digestive enzyme content and islet mass in adult Lewis rats and the ability of such pancreatic tissue dispersed by collagenase digestion without specific islet isolation to ameliorate diabetes when transplanted to the portal vein of syngeneic rats with streptozotocin induced diabetes. Rats fed normal chow supplemented with 0.5% DLE for 14-20 days showed a logarithmic loss of pancreatic mass. Total pancreatic amylase content declined to 0.3 + 0.1 mg, less than 3% of control values (14.3 +/- 1.0 mg). Total insulin content in DLE treated rats was 87 +/- 8 microg, not significantly different from control rats (101 +/- 7 microg). Histological examination confirmed the selective atrophy of exocrine tissue in DLE treated rats. Fresh pancreatic tissue prepared from a single DLE treated donor ameliorated diabetes 75% of the time when transplanted to one or two recipients and 65% of the time when divided between three of four recipients. Tissue prepared from a single DLE treated donor and stored for 24-48 hours ameliorated diabetes 91% of the time when divided between one or two recipients. Only four of 31 diabetic rats transplanted with fresh pancreatic tissue from untreated adult donors became normoglycemic. Pretreatment of adult rats with DLE induces selective exocrine atrophy, permits dispersed pancreatic tissue from a single donor to ameliorate experimental diabetes in up to four recipients, and allows tissue to be preserved by culture for up to 48 hours without specific islet isolation.

Amylases

Stable chimerism induced in noninbred rabbits by neonatal injection of spleen cells from allotype-suppressed adult donors. I. Replacement of hemopoietic tissue by donor cells.

In the course of experiments designed to demonstrate an active mechanism of allotype suppression in rabbits, spleen cells from adult donors were transferred to newborn recipients. Among 23 rabbits that received injections, 4 stable chimeras were formed, as determined by the production of serum immunoglobulins marked with light and heavy chain allotypes. The other rabbits that survived the immediate postinjection period displayed a temporary chimeric state lasting up to several weeks, after which they either succumbed to graft-versus-host disease or rejected the donor cells. One chimeric animal was apparently repopulated by the hemopoietic cells of the donor's spleen. Insofar as could be determined, the recipient's blood cells became phenotypically identical to those of the donor. This condition manifested itself as a loss of the recipient gene products associated with both lymphocyte and erythrocytes, accompanied by a seemingly total replacement with those of the donor.

Aging

[How healthy are our blood donors? Result of a liver screening in voluntary blood donors of Blutspendedienst Innsbruck].

A screening of hepatic function and HBs-antigen, made in 22344 voluntary blood donors in the bloodbank of Innsbruck, gave the following results: 0,33% HBs-AG negative donors were found to have pathological liverfunctiontests. Overweight and alcohol would be established as the most important etiological factors. 0,4% of the donors are carriers of the HBs-antigen. A control examination after 2 years showed a persistence of that antigenemia. Antigen carriers are requested to have regular examinations. Since HBs-AG positive hepatitis is not only transferred by blood and blood-constituents, it would be important to use the same screening methods applied in the blood donor organisation throughout any hospital area, to reduce the incidence of this disease.

Alcoholism

Synthesis of antibodies and immunoglobulins bearing recipient allotypic markers and donor idiotypic specificities in irradiated rabbits grafted with allogeneic cells from hyperimmune donors.

Irradiated rabbits were grafted with a mixture of bone marrow, lymph node and spleen cells from donors hyperimmunized against TMV. Recipient and donors were characterized by different a allotypic specificities. Antibodies synthesized in the recipients display allotypic markers from the recipients but idiotypic specificities cross-reactive with those of donor antibodies. The results show that the differentiation of new host B cells is influenced by the presence of donor memory cells and are interpreted in the light of network concepts.

Animals

Screening of blood donors for IgA deficiency: a study of the donor population of south-west England.

Altogether 29 745 English blood donors were screened for IgA deficiency by double diffusion analysis; 57 had apparent absence of IgA, a frequency of 1:522. Further examination by the more sensitive haemagglutination inhibition assay revealed 34 samples having no detectable IgA, a frequency of 1:875. All donors negative by double diffusion analysis were tested for the presence of antibodies to IgA. Six class specific anti IgA antibodies and four anti IgA antibodies of limited specificity were detected. Three of these had the specificity anti alpha2 and one anti A2m(2). The 34 IgA deficient donors detected provide a source of IgA deficient blood for transfusion to patients with anti IgA antibodies.

Antibodies, Anti-Idiotypic

[Detection of paraproteinemia in blood donors. Results of systematic analysis of 3800 donors in Trieste].

A systematic analysis of plasma protein pattern performed by agarose gel electrophoresis has detected paraproteinemia in 13 out of 3800 blood donors in the district of Trieste. The variations in the incidence of monoclonal gammopathies in surveys of blood donors could be related not only with geographical origin and the age and sex distribution of the population studied but also with the sensitivity of the screening technique employed. The physiopathological and clinical implications of the detection of paraproteins favour the inclusion of the screening plasma electrophoretic analysis among the laboratory investigations for blood donors.

Adolescent

Mastering the donor eye: a new device for obtaining donor corneal discs.

In recognition of the many inexactitudes involved in cutting donor corneal discs, a new instrument is here described which should help to eliminate many of then, and its mode of use is outlined. For a long time instruments available to assist the corneal surgeon in his management of donor material have been inadequate. Many devices are awkward to use, or give rise to donor discs of an unreliable or uneven edge profile. In an attempt to overcome these difficulties we have designed, produced and tested a new instrument which we feel represents an advance. Because different surgeons use fresh or stored material, and because some prefer to trephine from the epithelial surface while others opt to punch from the endothelium, we have endeavoured to meet all these requirements.

Corneal Transplantation

In a fully H-2 incompatible chimera, T cells of donor origin can respond to minor histocompatibility antigens in association with either donor or host H-2 type.

Fully H-2 incompatible radiation chimeras were prepared using BALB congenic mice. Such chimeric mice were immunized in vivo against histocompatibility antigens of the C57BL/10Sn (B10) background in association with either of the parental H-2 haplotypes, and their spleen cells subsequently boosted in vitro with the same minor antigens. Strong H-2-restricted cytotoxic activity against minor antigens was detected, and the specificity of the restriction could be to the H-2 haplotype of the donor or the host depending on the cells used for priming or boosting. Cross priming could also be demonstrated in these mice. The results show that fully allogenic radiation chimeras can produce H-2-restricted T-cell responses to minor histocompatibility (H) antigens, and are discussed in relation to contrasting results recently obtained against viral antigens.

Animals

Human skin grafts from mixed lymphocyte culture-positive donors provide help for the rapid rejection of simultaneously transplanted skin grafts from mixed lymphocyte culture-negative donors.

The influence of grafting more than one skin transplant simultaneously on one recipient was investigated. When a mixed lymphocyte culture (MLC)-negative skin was transplanted along with an MLC-positive skin, the MLC-negative skin survived for a significantly shorter time than when transplanted alone. This indicated that the MLC-positive skin provided a stimulus that could provide help to reject the MLC-negative skin. This finding might be important clinically. When an MLC-negative transplant is given to a patient, one should not transfuse this patient with MLC-positive leukocyte-rich blood.

Graft Rejection

Donor Microbiota Features Associated With Liver Transplant Recipient Infectious Complications: A Pilot Study Using Deep Intestinal Sampling During Liver Procurement.

BACKGROUND: The gut microbiota of living organ donors has been linked to transplant outcomes. However, little is known about the characteristics of the deceased donor gut microbiota or its potential impact on recipient outcomes. METHODS: We analyzed the deep intestinal microbiota from 24 deceased donors. Samples included luminal stool from the right and left colon as well as bile. Microbial composition was characterized using 16S V4 rRNA sequencing. &#x3b1;- and &#x3b2;-diversity analyses were performed to compare microbial communities between donor enteric sites and against stool samples from 28 healthy community controls, 14 critically ill intensive care comparators, and 12 matched liver transplant recipients. Machine learning models and logistic regression analysis were applied to explore whether features of the donor microbiota could predict recipient post-transplant complications. FINDINGS: The deceased donor microbiota showed an absence of the expected compositional variability between sampling sites, with no significant differences in either &#x3b1;- or &#x3b2;-diversity observed between bile, right and left colonic samples (all p > 0.05). Donor samples exhibited distinct microbial profiles compared with stool from both healthy and ICU comparators, including increased abundance of potential pathogens within the Enterobacteriaceae family (all p < 0.001). Features of the donor microbiota, particularly enrichment of Enterobacteriaceae, were associated with an increased risk of early post-transplant infection in recipients (&#x2264;&#xa0;30 days; p&#xa0;=&#xa0;0.011). INTERPRETATION: The deceased donor gut microbiota may represent a distinct microbial community with potential clinical relevance. Microbial profiling of donor enteric microbiota may help identify recipients at heightened risk of early post-transplant infectious complications.

Enterobacteriaceae

[Hepatologic dispensaire for blood donors].

By means of hepatological examinations of 119 blood donors who became conspicuous by liver screenings in 57 cases we could prove an adipose degeneration without, in 16 cases a fatty degeneration of the liver without, in 9 cases an adipose degeneration with and in 15 cases a fatty degeneration of the liver with mesenchymal reaction. Only 9 blood donors had normal liver findings. 90% of the punctured blood donors had an overweight up to a maximum of 35 kg in comparison to the ideal weight. 30% of the punctured patients admitted a clearly increased daily consumption of alcoholic beverages. By means of repeated punctures on 24 blood donors after 8 to 32 months after an adequate consultation in three cases a normalisation and in eight cases an improvement of the liver findings could be proved. In 13 cases the findings remained unchanged, also the anamnestic and clinical findings corresponded to this. In 2 blood donors by means of a threefold liver puncture in the observation period of 48 months also a clear retrogression of the liver findings was proved. With this was also connected the reduction of overweight and the avoiding of alcohol. Thus our investigations confirmed that overweight and abuse of alcohol are essential factors for the development of a fatty degeneration of the liver. Of an infectious hepatitis reported in the anamnesis in 10 blood donors histologically in no case residues were established. Thus the liver dispensary is of great importance for the care of blood donors who become conspicuous by screening tests. On the one hand the importance is referred to the blood donor himself, on the other hand to the group of donors. Blood donors taken out of the group could again be included in the special group, when after the exclusion of known noxae the retrogression of unspecific liver changes took place.

Adolescent

[Preventive-medicine screening methods in the examination of blood donors].

From a blood transfusion service with ca. 7000 donors a year, there was a loss of donors whose blood, having undergone medical tests, was found to be unsuitable. Details of all such donors were carefully documented. The results were ascertained by attentive control of the health of the donors which, in part, exceeded the minimum requirements laid down by the existing regulations. The relatively high loss of donors and the kind of disease underline the importance of these control checks, as an aspect of preventive medicine. This is of particular importance with regard to the results of so-called "new donors", who register for the first time. They had to undergo examination, and were only allowed to give blood when all the results of the tests had been submitted. The question then arises as to whether the regulations for the differing minimum requirements for the examination of "occasional donors" and "regular donors" can be maintained. A reduction of the expenditure on the present regulation examination of donors is not advocated because of both responsibility towards the blood donors, and in view of the increasing significance, to the medical care of patients, of the proximity of a clinic to an expedient transfusion service.

Anemia, Hypochromic