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Renal transplant arterial stenosis: amelioration of hypertension and improvement of transplant function after revascularization.

Two of 70 patients treated for a minimum of six months after renal transplantation developed main arterial stenosis to the allograft. Both underwent transplant revascularization and had follow-up at least six months to document lasting benefit. Amelioration of hypertension and improvement of transplant function proved statistically significant. Collateral vessels were not identified on pre-revascularization arteriographic studies. It is suggested that loss of the potential to develop protective collateral channels to transplanted kidneys mandates aggressive evaluation when hypertension and deteriorating renal function occur in the late follow-up period after renal transplantation. In such instances, arteriography and renin determinations may identify salvagable renal allografts, obviating necessity of subsequent retransplantation.

Adult

[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

Renal transplantation in congenital and metabolic diseases. A report from the ASC/NIH renal transplant registry.

The results of kidney transplantation in a variety of renal diseases have been analyzed. The diseases causing end-stage kidney failure in recipients were Alport syndrome, amyloidosis, cystinosis, diabetes mellitus, Fabry disease, familial nephritis, gout, medullary cystic disease, oxalosis, and systemic lupus erythematosus. The data indicate that renal transplantation is justifiable and parallels functional results for the more common causes of end-stage renal disease in all but Fabry disease and oxalosis. Although Fabry disease did not recur in any grafted kidney, only three patients have a functioning graft one year after transplantation. From a group of ten patients with oxalosis who received a total of 14 kidneys, only one survives. In no other metabolic disease, except one instance of primary amyloidosis, did the metabolic disease notably affect the transplant as it did in oxalosis.

Adolescent

Bone marrow transplantation from donors with aplastic anemia. A report from the ACS/NIH bone marrow transplant registry.

Bone marrow transplantation from HLA-matched allogeneic donors was used to treat two series of patients with severe aplastic anemia. No significant differences were detected in all comparisons made between the Registry series (38 patients) and the Seattle series (24 patients), and pooled data from the two series were used in the analyses. Currently, 55% of the patients who received bone marrow transplants within three months of diagnosis are alive, but only 13% of the patients who received bone marrow transplants more than nine months after diagnosis are alive. The difference between the two groups was significant (P less than .02). Patients less than 21 years of age had a significantly higher survival rate than those patients who were 21 years or older at the time of transplantation (P less than .02). Survival rates were significantly higher for patients who had received 15 or fewer pretransplant transfusions than those who received more (P less than .05).

Adolescent

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

Significance of HLA matching in renal transplantation. A prospective one-center study of 485 transplants matched or mismatched for HLA-A, B, C, D, and DR antigens.

Matching for HLA haplotypes as well as for HLA-A and B antigens improved graft survival in 112 living related first transplants. In cadaveric first transplants, matching for HLA-A and B antigens had a beneficial effect on the fate of 373 grafts, while matching for HLA-C antigens had no predictive value. One hundred seventeen cadaveric transplants and their recipients were prospectively typed for the HLA-DR antigens. Compatibility for HLA-DR was found to be prognostically beneficial irrespective of matching for HLA-A and B antigens, and with no difference between transfused and nontransfused patients. Matching both for HLA-A , B and D/DR was thus found to influence the outcome of renal transplantation.

Adult

Duration of Hospitalization is Associated with the Gut Microbiome in Patients Undergoing Hematopoietic Stem Cell Transplantation: Early Results from a Randomized Trial of Home Versus Hospital Transplantation.

Home-based hematopoietic stem cell transplantation (HCT) is an innovative care model with growing interest, but its impact on the gut microbiome remains unexplored in a randomized setting. We present interim results from the first randomized controlled trials (RCT) evaluating the effect of HCT location-home versus hospital-on gut microbial diversity and antimicrobial resistance (AMR) gene carriage. We hypothesize that patients randomized to undergo home HCT would have higher gut taxonomic diversity and lower AMR gene abundance compared to those undergoing standard hospital HCT. We analyzed stool samples from the first 28 patients enrolled in ongoing Phase II RCTs comparing home (n = 16) and hospital (n = 12) HCT at Duke University using shotgun metagenomic sequencing to compare taxa and AMR gene composition between groups. We also performed a secondary analysis comparing patients who received transplants at outpatient infusion clinics versus inpatient standard HCT to evaluate the influence of hospitalization duration. In the primary RCT analysis, taxonomic and AMR gene α- and β-diversity were comparable between home and hospital groups, reflecting similar durations of hospitalization despite group allocation. In contrast, secondary analyses demonstrated that patients transplanted in outpatient infusion clinics who experienced significantly reduced hospitalization had higher gut taxonomic α-diversity and differential β-diversity, although AMR gene diversity remained unchanged. In summary, randomization by transplant location did not impact the gut microbiota to the same extent as the duration of hospitalization, although secondary analyses were heavily confounded. Even when taxonomic differences were observed, AMR genes were similar between groups. This RCT represents a novel investigation into how care setting influences the gut microbiome during HCT. Our findings suggest that hospital duration, rather than randomization allocation alone, is the primary driver of microbial disruption. These results underscore the potential for reducing hospital duration to mitigate microbiome injury, thereby informing future interventions to reduce infection risk and improve patient outcomes.

Microbiome

Transplantation haemopoiesis. Morphological bone marrow studies after allogeneic marrow transplantation in man for severe aplastic anaemia and acute leukaemia.

Bone marrow (BM) morphology was studied in patients who underwent bone marrow transplantation (BMT) for severe aplastic anaemia (SAA) and acute myeloid leukaemia (AML). Four patients with SAA had marrow transplanted from HLA-identical siblings after conditioning with cyclophosphamide (CY); three cases of AML were treated with allogeneic BMT. The medullary material was generally obtained by aspiration, but treated so as to preserve its architecture; fresh, postvital preparations were particularly useful for this purpose. In SAA, the bone marrow before transplantation showed dense infiltrates composed of macrophages and other inflammatory cells; after BMT, repopulation started at the periphery of the infiltrates, when they were not totally destroyed by CY. Granulocytic repopulation generally preceded erythropoiesis, which always occurred by way of typical erythroblastic reticulocytopoietic islands. Marked but transient dyserythropoiesis was found in two cases; in one of them, it was considered as drug-dependent. Both in SAA and in AML, but more so in the latter, a marked and sometimes imposing macrophagic hyperplasia was found after transplantation. Many macrophages were actively engulfing erythrocytes and nucleated cells. This last type appeared prominent in rejection episodes.

Anemia, Aplastic

[Dura transplantation. Multi-sequential transplants of solvent dehydrated dura mater. Animal experiment studies on the question of sensitization].

After the excision of 7 X 5 mm abdominal muscle sections in an experiment using rats, a total of 4 xenogenic, solvent dehydrated dura mater of the same size were implanted at 4 week intervals each. The transplant areas were continuously examined under a light and electron microscope for a period ranging from 7 days up to 3 months after the last transplant. Spontaneous layers of absorbent granulation tissue, rich in cells and blood vessels, surrounded the grafts in the beginning. Subsequently the grafts were gradually decomposed from the periphery to the center through macrophages like biological foreign matter and replaced with endogenous, poorly vascularized, collagenous connective tissue. The tissue reaction to the multi-sequential, xenogenic grafts was consistently the same as after single transplants. Immuno-competent cells do not increase. The solvent preserved dura mater is suited for multisequential transplants due to lacking sensitization, i.e. immunological rejection reaction.

Animals

Association between pre-transplant natural kill and graft-versus-host disease after stem-cell transplantation.

Natural killer activity against herpes simplex virus type 1 infected fibroblasts NK(HSV-1) was studied prospectively in patients undergoing allogenic bone-marrow or fetal-tissue stem-cell transplantation. Thirteen patients showed evidence of engraftment and survived long enough to develop graft-versus-host disease (GvHD). Of this group, all of the seven having normal NK(HSV-1) activity before transplantation acquired GvHD and the six having low NK(HSV-1) had no evidence of GvHD. These results were independent of mode of preparation of patients for transplantation, source of stem cells used, or cytomegalovirus infections, and they suggest that this assay reflects a host-determined function capable of stimulating GvHD.

Anemia, Aplastic

Renal transplantation between HLA identical siblings. Comparison with transplants from HLA semi-identical related donors.

We compared 26 HLA-A, B identical sibling kidney-transplant recipients followed for one to 10 years, with 104 HLA-A, B semi-identical kidney recipients from living, related donors to determine clinical differences. Graft-survival rates were significantly better in the HLA identical group at two years (85 per cent identical versus 53 per cent in semi-identical, P less than 0.005); patient-survival rates were high for both (96 per cent in identical and 87 per cent in semi-identical at two years, P less than 0.005). The incidence of complications was similar in HLA identical and semi-identical recipients. Nine of the 26 grafts in HLA identical recipients failed one week to eight years after transplantation. Rejection caused most of the graft failures. Recipients of HLA identical-sibling kidney transplants have a high patient and graft survival, but they also encounter many complications. Immunologic rejection occurs, even with negative mixed lymphocyte culture, suggesting the importance of donor determinants other than the HLAA, B and D other than the HLA-A, B and D.

Acute Disease

Transplantable osteosarcoma in mice. Structural characterization of a transplantable osteosarcoma obtained in an allogenic system.

Light microscopic, histochemical and ultrastructural studies of a transplantable mouse osteosarcoma were carried out. The osteosarcoma grew in CBA mice after injection of cultured cells derived from a Dunn osteosarcoma. The tumour differed from the original Dunn osteosarcoma with respect to metastatic potential and structural features. The transplantable tumour was an anaplastic, richly vascularized fibroblastic osteosarcoma with alkaline phosphatase activity and rather sparse osteoid formation, resulting in death of the animals within 6 to 8 weeks. Virus particles were found intracellularly, mainly localized to cisterns of rough endoplasmic reticulum, and extracellularly often close to plasma membranes and collagen fibres. Sign suggestive of formation of collagen fibres by tumour cells were observed. A possible viral influence upon the tumour was suggested also by its growth behaviour in vitro. The results indicate that this new transplantable tumour, obtained in an allogenic system, represents a clonal derivative of the original Dunn osteosarcoma.

Animals

[Renal transplantation in patients suffering from Fabry's disease. Kidney transplantation from an heterozygote subject to a subject without Fabry's disease].

We report the case of a renal transplantation performed with the kidney of an asymptomatic female carrier of Fabry's disease. The recipient, her daughter, had normal alpha-galactosidase levels. Eight years after transplantation, the characteristic lesions of the glomerular epithelial cells, noted as early as 11 days after transplantation, are unchanged on the successive biopsies. This observation suggests that 1) some heterozygotes (perhaps all of them) have glomerular changes, 2) the glomerular changes are not modified if the kidney is placed in a normal enzymatic "environment".

Adult

Antibody response to horse gamma-globulin in recipients of renal allografts: relationship with transplant crises and transplant survival.

Anti-antilymphocyte globulin (ALG) antibody response was measured every day during and after ALG treatment in 52 recipients of renal allografts. IgM antibodies became detectable in 37 patients, usually at day 8 and IgG antibodies appeared 3 days after the IgM in 21 of 37 cases. Of 30 transplant crises recorded between days 6 and 11, 20 coincided with the onset of the antibody response, and the incidence of crises during this period was higher among antibody producers than among nonproducers. In 31 patients a partial or total unresponsiveness to ALG could be achieved. Transplant survival at 3 months was better in this group than among good responders (P less than 0.01). Anti-ALG antibody response may then be usable as an early indication of individual differences in reactivity against transplant antigens.

Animals

Osteogenesis after bone and bone marrow transplantation. II. The initial cellular events following transplantation of decalcified allografts of cancellous bone.

An experimental study was done in rabbits to investigate the fate of allogeneic iliac cancellous bone, both non-decalcified and decalcified with hydrochloric acid, transplanted to a muscular site for up to 14 days. Some of the treated allografts were impregnated with autologous bone marrow cells, obtained from the femoral medulla by aspiration, and each was compared with allografts alone. Combined myelo-osseous grafts produced bone after 7 to 8 days implantation, as did marrow autografts alone. In addition non-decalcified implants stimulated the production of multinucleated giant cells. Three different types of wash solution were used but these did not inftical events in bone formation after transplantation occur less than 8 days after tho the clinical aspects of bone grafting.

Animals

[A new method of pancreatic transplantation. II. Double renal and pancreatic transplantation in a diabetic with renal failure (author's transl)].

A 41-year-old man who had suffered from insulin-dependent diabetes since the age of twenty and who had severe degenerative complications with chronic renal failure, underwent pancreatic transplantation. The graft was prepared by intraduct injection of neoprene in order to suppress the exocrine function of the gland. It was situated in the iliac fossa and has ensured the complete correction of diabetes for more than 10 months. This favourable situation made it possible to carry out a renal transplant which could not have been envisaged previously in this patient with very unstable and progressive diabetes who was dialysed under very difficult conditions.

Adult

Squamous cell carcinoma of the tongue in a nine year renal transplant survivor: a case report with a discussion of the risk of development of epithelial carcinomas in renal transplant survivors.

A case of squamous cell carcinoma of the tongue in a 26-year-old man developing nine years after renal transplantation is presented. This is the first such case to be reported. Within seven months, widespread tumor metastases resulted in death. Pathologic examination of the transplanted kidney demonstrated neither re-establishment of glomerulonephritis nor evidence of rejection, and lack of significant renal disease was confirmed by electron microscopy. This long term survival without development of renal pathology is also of great interest.

Adolescent