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Frequency and Distribution of KIR Genotypes of Donors-Recipient Pairs in the Haploidentical Haematopoietic Stem Cell Transplantation Setting: Collaborative Study by the Spanish Working Group in Histocompatibility and Transplant Immunology (GETHIT) and the Spanish Haematopoietic Transplantation and Cell Therapy Group (GETH-TC).

There is limited information regarding the influence of KIR genotype, compared to the HLA system, in haploidentical haematopoietic stem cell transplantation (haplo-HSCT). This study aimed to determine the frequencies of KIR genotypes in Spanish haematologic patients undergoing haplo-HSCT. A study was conducted on 113 oncohaematological patients and their donors, treated across five centres that are members of the Spanish Working Group in Histocompatibility and Transplant Immunology (GETHIT) and the Spanish Haematopoietic Transplantation and Cell Therapy Group (GETH-TC). KIR typing was performed using PCR-rSSO or PCR-SSP. KIR genotypes were identified using the KIR Allele Frequency Net Database. Among donors, the most frequent KIR genotypes were Type 1 (28.3%), Type 2 (12.4%) and Type 4 (10.6%). In patients, Genotypes 1 (23.9%), 4 (23%) and 2 (14.2%) were most prevalent. Donors exhibited AA centromeric (46%) and telomeric (59.3%) types, while patients had a higher AB centromeric frequency (52.2%). Differences were observed in the BB centromeric type (3.5% patients; 16.8% donors, p = 0.002). The AB KIR genotype was the most common (70.8% donors; 75.2% patients). Most were classified as 'neutral' (61.9% donors; 73.5% patients). B-content score1 was the most common (48.7% patients; 33.6% donors). Notably, classification as best was rare (2.7% patients; 16.8% donors, p = 0.002). The study highlights the distribution of KIR genotypes in haplo-HSCT patients and donors, with Genotypes 1, 2 and 4 being the most prevalent. AB KIR genotypes and B-content score 1 were dominant. Moreover, KIR genotypes ID may serve as criteria for future investigation about the immunogenetic predisposition to malignant haematological diseases.

Humans

Dynamic renal transplant imaging with Tc-99m DTPA (Sn) supplemented by a transplant perfusion index in the management of renal transplants.

We have performed 955 studies on 152 patients with 167 renal transplants. Images were recorded following bolus injection of 12-15 mCi Tc-99m DTPA (Sn). The data were stored on a computer and analyzed by generation of region-of-interest curves from (a) the iliac artery distal to the transplant, (b) the kidney, and (c) a background area. A perfusion index was adopted: formula see text. In 276 studies the patient clearly had acute tubular necrosis (ATN), rejection, or a normal kidney on retrospective analysis. The normal perfusion index has a value below 150, and it increases with falling perfusion, such as is seen in rejection and in renal-artery stenosis. The use of this index in addition to sequential images and changes in the region-of-interest curves usually allows separation of rejection from ATN and, particularly, rejection from normals. When serial studies are performed, the separation of rejecting from nonrejecting transplants is excellent, although renal-artery stenosis may cause similar changes in perfusion.

Acute Kidney Injury

Subcutaneous, isogeneic transplantation of duct-ligated pancreas in streptozotocin diabetic mice: relationships between recovery and hormone contents in transplants or host pancreas.

Recovery from diabetes was observed in streptozotocin-treated mice that received subcutaneous, isogeneic transplants of duct-ligated pancreas. Transplants excised from recovered hosts contained both immunoreactive insulin (IRI) and glucagon (IRG), indicating that both A and B cells capable of hormone storage were present. The IRI content in transplants, although only one sixth of that transplanted 6 wk earlier, was still 21/2 times greater than that in the host pancreas and was inversely related to the plasma glucose of the recipient during and after recovery. The IRI content in the transplant added to that in the host pancreas totaled 13% of the IRI found in the normal mouse pancreas, which sufficed for over-all recovery from diabetes but was insufficient to provide normal glucose tolerance and insulin response to a major glucose challenge. The abnormally high content of glucagon noted in the pancreas of hyperglycemic, sham transplanted mice was reduced by one-half in the pancreas of those transplanted mice returning to normal plasma glucose and insulin. Thus, the insulin content of the transplant was important to the recovery of isografted mice, but in addition, and perhaps as a consequence of recovery, there was a slight increase in the insulin storage capacity of the host pancreas and a marked reduction of glucagon compared to the content of these hormones in the pancreas of hyperglycemic, sham transplanted mice.

Animals

Should we consider excessive weights in pediatric kidney transplant recepient candidates?: A systematic review and meta-analysis of kidney transplantation outcomes.

INTRODUCTION: In adult populations, excess body weight has been associated with an increased risk of adverse clinical outcomes and mortality following kidney transplantation. In contrast, the influence of obesity on transplantation outcomes among pediatric populations is not yet fully understood. This study aimed to evaluate the association between pre-transplant excess weight and post-transplant outcomes in pediatric kidney transplant recipients. MATERIAL & METHODS: A systematic literature search was performed across PubMed, ScienceDirect, and the Cochrane Library, covering publications up to December 31, 2025. The quality of the included studies was evaluated using the ROBINS-E tool. Statistical analysis was conducted using Review Manager version 5.4. RESULTS: From a total of 1465 records screened, six studies that included 65,483 participants were selected in the meta-analysis. The results indicated that pre-transplant excess weight was significantly associated with an increased risk of acute rejection (OR = 1.09; P = 0.009), delayed graft function (OR = 1.17; P < 0.00001), 1-year graft failure (OR = 1.16; P = 0.0002), and 5-year graft failure (OR = 1.13; P = 0.009). Although 5-year mortality was also higher among recipients with excess weight, this association was not statistically significant (OR = 1.08; P = 0.11). CONCLUSION: Pediatric patients with pre-transplant excess weight had higher post-transplant odds of acute rejection, delayed graft function, and both 1-year and 5-year graft failure compared to those without excess weight. These findings highlight the importance of assessing and managing excess weight prior to kidney transplantation to help prevent adverse outcomes in the future.

Humans

Trimethoprim/sulfamethoxazole-triggered drug-induced hypersensitivity syndrome in an HLA B*13:01-positive kidney transplant recipient: a case report with implications for HLA-severe cutaneous adverse reaction associations in transplant care.

Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is a severe cutaneous adverse reaction (SCAR) with a reported mortality rate of approximately 2-10%. DIHS/DRESS typically develops 2-8 weeks after exposure to an offending drug. An important focus of contemporary SCAR research is the growing evidence that specific human leukocyte antigen (HLA) alleles confer a markedly increased risk of drug-specific hypersensitivity reactions. We report a case of a kidney transplant recipient who developed DIHS/DRESS after prolonged trimethoprim/sulfamethoxazole (TMP/SMX) prophylaxis and carried the HLA-B13:01 allele. HLA-B13:01 is a strong genetic risk factor for TMP/SMX-induced DIHS/DRESS, particularly in Southeast Asian populations. Herein, we highlight the potential clinical relevance of pre-transplant HLA typing in predicting SCAR risk in transplant recipients. TMP/SMX-associated DIHS/DRESS may be under-recognized in transplant settings, where awareness of HLA-associated risk remains limited despite robust evidence from non-transplant populations. Transplant clinicians should be aware that DIHS/DRESS can occur outside the typical latency period, especially during immunosuppressant tapering, highlighting the need to integrate pharmacogenomic risk assessments into transplant care.

Humans

[Experimental and clinical aspects of the living articular cartilage transplantation and half-joint transplantation (author's transl)].

The articular cartilage transplantation and the half-joint transplantation necessitate the assessment of specific biological-transplantation questions as to the structure and function of the hyaline cartilage. Compared with other organ transplantations biometric and biomechanical factors have to be taken into consideration additionally. Up to now contradictory results were obtained in the animal experiment. On principle a survival of grafted non-preserved parts of cartilage seems to be possible. In clinical practice therapeutic trials for autogenous reimplantation of articular cartilage, autogenous joint surface partial transplantations and half-joint transplantations are justified. Allogenous half-joint transplantations may also be possible in exceptional cases.

Adolescent

Syngeneic transplantation of fetal rat pancreas. II. Effect of insulin treatment on the growth and differentiation of pancreatic implants fifteen days after transplantation.

Eight 18-days-postcoitum fetal pancreases were transplanted to isogenic alloxan-diabetic male rats. Some recipients were treated with insulin for seven days immediately after transplantation. Eight animals in both the insulin-treated group and control group were killed 15days after transplantation for morphologic and hormonal studies of the transplanted tissue. Using the morphometric technique of linear scanning, the insulin, glucagon, and somatostatin immunocytochemically positive, cell masses of the fetal pancreatic implants were quantitated. The beta cell mass of the implants from the control animals increased roughly eightfold from the time of transplant; insulin treatment resulted in a further two- to threefold increase. The insulin content of the implants increased more than did the beta cell mass, resulting in the fivefold increase in insulin per beta cell. The alpha cell and delta cell masses did not change during the transplant site, the mass of functional beta cells, and the cell-to-cell content of the implanted tissue. These results are discussed in relation to previous quantitative studies of pancreatic islet cell growth. The relationships of the transplant site, the mass of functional beta cell, and the cell-to-cell interaction within the islet to the maintenance of glucose homeostasis are also discussed.

Animals

Hepatocellular transplantation --morphological study on hepatocytes transplanted into rat spleen--.

Hepatocellular transplantation into the spleen was investigated as a new attempt in utilizing isolated hepatocytes to compensate for impaired liver function. Present study was undertaken to evaluate morphological and histochemical alterations up to 6 weeks following transplantation in hepatocytes transplanted into the splenic parenchyma. Light microscopic studies revealed viable hepatocellular islets in the splenic parenchyma up to 6 weeks, although minimal cytoplasmic changes were observed. Electron microscopic studies demonstrated moderate changes in organelles, which developed gradually as the time after transplantation proceeded. Distortion and fragmentation of the membranes around the cytoplasm and organelles were not recognized. Moreover, newly formed bile canaliculi and tight junctions which indicate reconstruction of hepatic plates were observed between adjacent cell membranes, and enzyme activities were detected by cytochemical determination of glucose-6-phosphatase in the hepatocytes even 6 weeks after transplantation. The transplanted hepatocytes preserved their characteristic enzyme and fine structures as hepatocytes up to 6 weeks. Our present study based on the persistence of cellular viability suggests that inoculated hepatocytes do maintain their hepatocellular functions after transplantation.

Animals

Kidney transplants in mice. An analysis of the immune status of mice bearing long-term, H-2 incompatible transplants.

Kidney transplants between strains of mice which are incompatible at either the K or the D end of the H-2 complex usually function for prolonged periods supporting the lives of nephrectomized recipients. This occurs with no recipient treatment. With multiple H-2 and non-H-2 determined incompatibilities, transplants may be rejected but more slowly than skin grafts. In the strain combination studied most extensively in these experiments (B10.D2 to B6AF(1)) in which the incompatibility was confined to the K end of the H-2 region, about 70 percent of recipients survived for many weeks with normal blood urea nitrogen levels. Skin grafts between untreated members of these strains were rejected promptly (mean survival time of 13.5 +/- 1.1 days) as were kidney transplants to recipients of prior skin grafts. Donor strain skin grafts to recipients of kidney transplants after kidney transplantation enjoyed greatly prolonged survival whereas skin grafts from a third party (A.SW) were rejected normally. If kidney tissue was transferred in the form of free grafts without primary vascular union, it was rejected promptly leaving its recipient highly immunized. Cellular and humoral immunity to donor antigens declined over the first few weeks after transplantation, and the spleens of long-term recipients contained no "killer cells." Recipient lymphoid cells could mount active graft versus host reactions to donor strain antigens on transfer to neonatal mice. Nevertheless, they were distinctly less able to respond specifically by the production of killer cells to donor strain antigens after sensitization in vitro. No evidence that this defect was associated with the presence of suppressor cells was forthcoming from several types of in vivo and in vitro tests.

Animals

HLA-A&#x2009;&#x2217;01:01 Allele Is Associated With Increased Risk of Transplant-Related Mortality After MHC Matched Unmodified Allogeneic Hematopoietic Stem Cell Transplantation.

Acute graft-versus-host disease (aGvHD) remains a substantial cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (allo-HCT). Limited studies explore the association between specific major histocompatibility complex (MHC) alleles and aGvHD or transplant-related mortality (TRM). After a noted clinical trend of higher TRM among a series of patients with aGvHD and MHC class I HLA-01:01, we retrospectively evaluated transplant outcomes of 404 adult allo-HCT patients who underwent unmodified allografts between 03/2010 and 02/2017. HLA-01:01 was expressed by 104 (25.7%) patients. In a univariate analysis, patients who underwent unmodified transplants and expressed HLA-01:01 had a higher risk of TRM (HR 1.63 [95% CI: 1.05-2.53], p = 0.035). In a multivariate cause-specific Cox model, HLA-01:01 was significantly associated with TRM after adjusting for grade II-IV aGvHD, conditioning regimen intensity, and age at transplant (HR 1.59 (95% CI: 1.02-2.48) p = 0.039). There were no significant differences in overall survival (OS), aGvHD, or chronic GvHD based on HLA-01:01 expression. With confirmation in a larger cohort, these findings have potential implications for the selection of allograft type, conditioning regimen, and post-transplant monitoring for this high-risk population.

Humans

Parent-to-child and child-to-parent kidney transplants. Experience with 101 transplants at one centre.

101 first transplants were done in patients with end-stage renal disease using kidneys from parents or offspring. All patients were followed up for at least two years, and the absolute two-year patient-survival rate was 88% and the two-year functional-kidney rate was 79%. Actuarial statistics at four years were 82% for survival and 67% for function in the parent-to-child group. In the child-to-parent group absolute patient survival was 83% and transplant function was 79% at two years; these results were unchanged at four years. Thus, transplants from parents to children or from children to parents are much the same despite differences in age. There is some advantage in parent-to-child transplants from being female but no advantage in being diabetic, receiving higher or lower doses of antilymphocyte globulin, or sharing more than two HLA antigens with the donor. Mismatched sibling transplants survived approximately as well as did grafts from parents to children and children to parents. These results, taken in concert with the poor results of cadaver transplantation, the relative safety of donation, the high personal motivation to donate in these groups, and the personal satisfaction derived by the donor, strongly support the policy of informing potential recipients of the benefits of parental or offspring kidney donation.

Adolescent

The significance of body sodium content in hypertension following renal transplantation: exchangeable sodium and plasma renin concentration before and after renal transplantation.

The purpose of the present study was to determine the importance of body sodium content in hypertension following renal transplantation using measurements of exchangeablesodium (NaE) before and after transplantation. Plasma renin concentration (PRC) was also investigated. In the present study the necessity of a reference for expressing NaE values was eliminated because the subjects investigated acted as their own controls. The study included fourteen recipients, of whom seven were normotensive with an average blood pressure (BP) of 136/84 mmHg and seven were hypertensive with an average BP of 182/113 mmHg after renal transplantation. In the hypertensive NaE increased significantly (mean 22%) in contrast to an insignificant decrease in NaE in the normotensives (mean, -5%). The change in NaE was positively correlated to the mean BP after renal transplantation (p = 0.69, n = 14, P less than 0.02). BP and NaE were not correlated to prednisone dosages. PRC was normal in all the hypertensives. The results strongly suggest that sodium accumulation in the body, which is not prednisone-dependent, is involved in the pathogenesis in post-transplant hypertension.

Adult

Late failure or human renal transplants. An analysis of transplant disease and graft failure among 125 recipients surviving for one to eight years.

The purpose of the present paper was to study clinical, morphological and immunological aspects of late rejection of renal allotransplants. We have, therefore, analyzed the occurrence and nature of renal transplant disease and graft failure among 125 recipients surviving for 1 to more than 8 years after transplantation. In this population transplant disease as defined by the appearance of heavy proteinuria and/or steadily declining graft function occurred in 22 patients. At the closure date of the study on December 31, 1972 complete graft failure had occurred in 12 of these 22 patients and 4 of these have died. In addition two patients died in the presence of normal graft function, due to chronic hepatitis and metastatic cancer respectively. As based on clinical findings, pathophysiological features and renal lesions the patients with late transplant disease were classified into two groups and described accordingly. Group A, termed glomerular transplant disease, included a majority of 16 patients, constituting a rather homogenous idsease entity in relation to course of disease, clinical findings and renal lesions as studied by light-, immunofluorescence- and electron microscopy. All these patients presented with heavy proteinuria, which was non-selective in all but two, resulting eventually in complete loss of graft function in eight cases. All these patients developed hypoalbuminemia and hypercholesterolemia, and one half manifested a classical nephrotic syndrome. Arterial hypertension occurred in all patients except two. Glomerular structure as studied by light microscopy revealed a number of lesions of a rather polymorphous pattern in all patients in group A. Endomesangial proliferation, hyperplasia and segmental proliferation of epithelial cells and thickening of capillary walls were prominent features, although the degree of severity, extension and type of lesion occurred in such varying proportions that classification into any well characterized category of glomerulonephritis was not possible. All cases in group A revealed immune deposits, most frequently containing IgG, IgM, complement and fibrinogen. IgA, IgD and IgE were also demonstrated in a lesser proportion of cases in this group. The immunofluorescent pattern was a mixed granular and linear, and in no case strictly linear or granular alone. The ultrastructural investigation contains a detailed analysis of the

Adult

Effect of adding umbilical cord blood derived stem cells to haploidentical stem cell transplant (haplo-cord) on post-transplant survival and graft-versus-host disease in patients with hematological malignancies: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Haploidentical stem cell transplantation (haplo-SCT) carries a substantial risk of graft-versus-host disease (GvHD), whereas umbilical cord blood (UCB) transplantation offers lower GvHD risk but slower engraftment. The haplo-cord approach combines both graft sources, aiming to mitigate GvHD while ensuring timely engraftment. This meta-analysis compares haplo-cord transplantation with haplo-SCT alone for the treatment of hematological malignancies. METHODS: Four electronic databases and two clinical trial registries were systematically searched. Effect sizes from eligible studies were pooled using odds ratios (ORs) for dichotomous outcomes and hazard ratios (HRs) for time-to-event outcomes. RESULTS: Twelve studies met the inclusion criteria. Haplo-cord was associated with a statistically significant reduction in chronic GvHD (OR&#xa0;=&#xa0;0.62, 95%-CI: 0.42-0.93), while no significant difference was observed for grade II-IV acute GvHD (OR&#xa0;=&#xa0;0.75, 95%-CI: 0.52-1.09). Survival outcomes favored haplo-cord, with lower HRs for overall survival (HR&#xa0;=&#xa0;0.68, 95%-CI: 0.53-0.86) and event-free survival (HR&#xa0;=&#xa0;0.61, 95%-CI: 0.52-0.72), while non-relapse mortality was not significant. Relapse at 3&#xa0;years was significantly lower with haplo-cord (OR&#xa0;=&#xa0;0.54, 95%-CI: 0.35-0.82). Haplo-cord also demonstrated higher day-30 engraftment, along with lower relapse-related and GvHD-related mortality, while CMV and EBV viremia showed no difference between groups. CD34 selection in the haplo graft significantly influenced effect sizes and heterogeneity in both subgroup analyses and meta-regression for acute GvHD. CONCLUSION: Haplo-cord transplantation improves GvHD outcomes, survival, and relapse risk compared with haplo-SCT alone. However, whether protocol optimization, possibly via CD34 selection, confers additional benefit remains uncertain and requires confirmation in future studies.

Humans

[Kidney transplantation from a nephrological-urological viewpoint--results and problems. 2. Diagnosis and therapy after transplantation, complications, long-term results].

Indications, selection of donor and recipient, medical and surgical management and complications, problems of organ procurement. Renal transplantation has become routine therapy. Organs are predominantly obtained from cadavers, transplantations from living donors are rarely indicated. Advances in preservation methods have improved organ quality and prolonged storage time. Selection of the most suitable recipient is based on histocompatibility matching. Blood transfusions before transplantation seem to improve the results. Recognition of a rejection crisis is primarily based on clinical symptoms. Persistent rejection calls for prompt explantation and the patient has to return to dialysis. Infections, serum-hepatitis and gastro-intestinal bleeding are the most common complications. Late complicatons are diabetes mellitus, cirrhosis of the liver, osteopathy, recurring glomerulonephritis, and, rarely, malignomas. Transplantation frequency in the Federal Republic of Germany could be increased by more awareness of physicians and a better knowledge of the general public about the need for cadaver donors.

Graft Rejection

Comparison of the immunologic reactions of arterial transplants in the arterial system and of venous transplants in the venous system using inbred strains of rats.

(1) Arterial transplants used as arterial replacements induce sensitization of the recipient in the weakly as well as in the strongly allogeneic systems (afferent limb). (2) Venous transplants used as venous replacements induce sensitization of the recipient (afferent limb). (3) Arterial transplants show increasingly severe rejection reactions paralleling the degree of immunogenetic difference (efferent limb). (4) Veins transplanted as venous replacements are tolerated even in the strongly allogeneic systems (efferent limb).

Animals

Islet transplantation in experimental diabetes of the rat. IV. The influence of transplantation site and of histocompatibility on islet function.

Experimental islet transplantations in pancreatectomized and streptozotocin-treated diabetic allogeneic and partially inbred rats are considered with respect to transplantation site and immunological factors responsible for survival. It could be shown that transplantation into the liver and into the lung in both systems (allogeneic and partially inbred) was accompanied by longer survival of the islets compared with the following regions: subcutaneous tissue, muscle, epididymal fat tissue, peritoneal cavity. This indicates that not only immunological but also factors of blood supply (oxygen consumption?)play a role in the survival of the grafts. - The success of transplantation depends mainly on histocompatibility. Partially inbred rats showed significantly longer survival of islets than non-inbred rats. The studies of other groups using similar experimental models are reviewed.

Animals