Showing papers on "Transplantation published in 1985"

The Quality of Life of Patients with End-Stage Renal Disease

Abstract: We assessed the quality of life of 859 patients undergoing dialysis or transplantation, with the goal of ascertaining whether objective and subjective measures of the quality of life were influenced by case mix or treatment. We found that 79.1 per cent of the transplant recipients were able to function at nearly normal levels, as compared with between 47.5 and 59.1 per cent of the patients treated with dialysis (depending on the type). Nearly 75 per cent of the transplant recipients were able to work, as compared with between 24.7 and 59.3 per cent of the patients undergoing dialysis. On three subjective measures (life satisfaction, well-being, and psychological affect) transplant recipients had a higher quality of life than patients on dialysis. Among the patients treated with dialysis, those undergoing treatment at home had the highest quality of life. All quality-of-life differences were found to persist even after the patient case mix had been controlled statistically. Finally, the quality of life of transplant recipients compared well with that of the general population, but despite favorable subjective assessments, patients undergoing dialysis did not work or function at the same level as people in the general population.

HLA and disease associations

Abstract: The human leukocyte antigen (HLA) or tissue types are the products of a rapidly developing field of knowledge within the last 20 years. In the early stages of the research many investigators suspected the existence of a complex series of transplantation antigens, but it was widely believed that these antigens would not be well-defined even in this century. Yet in the last two decades as many as 124 different HLA antigens determined by at least 7 very closely linked genes located on the short arm of chromosome 6 have been identified and subsequently agreed upon by an international nomenclature committee. 1 Extensive international collaboration fueled by the potential clinical application of these antigens to clinical transplantation has advanced the field rapidly. There were nine inter national histocompatibility workshops held during this period. Although iden tification of HLA antigens was of primary clinical importance in transplantation 2 and of great basic interest in human genetics and anthropology, a rather un expected bonus has been the determination that HLA antigens are associated with disease susceptibility to a greater extent than any other known genetic marker in man. In the past, many genetic polymorphisms have been suspected to be associated with diseases. The most extensively studied markers are blood groups, enzymes, and serum proteins. A comprehensive account of published studies, totalling approximately 1,000, of these markers is available in a book by Mourant et al."

A highly polymorphic DNA marker linked to adult polycystic kidney disease on chromosome 16

Abstract: Adult polycystic kidney disease (APCKD) is a common and often lethal multi-organ disease with an autosomal dominant pattern of inheritance; approximately 1 in 1,000 people carry the mutant gene1. The major pathological abnormality is the development and progressive enlargement of cysts in several organs including the liver, pancreas and spleen as well as the kidneys. The basic biochemical defect which leads to the formation of cysts remains unknown2. Cyst development, which is not retarded by any known therapy, leads to irreversible renal failure and death at a mean age of 51 unless dialysis or transplantation are used3. Patients with the disease account for 9% of chronic dialysis requirement4. The first symptoms tend to occur in the fourth decade, after most patients have reproduced3. Presymptomatic diagnosis depends on the ultrasonographic detection of cysts, but exclusion cannot be achieved by this means; 34% of at-risk patients in the second decade and 14% in the third will go on to develop cysts after negative diagnosis5. The low sensitivity of diagnostic techniques in this critical age-range imposes severe limitations on genetic counselling and the condition cannot be identified prenatally. Hence we have searched for a linkage marker for APCKD; we show here that the APCKD locus is closely linked to the α-globin locus on the short arm of chromosome 16 (ẑ = 25.85, θ=0.05).

Down-Regulation of the Antitumor Immune Response

Abstract: Publisher Summary This chapter discusses the immune response to chemically induced, transplantable tumors in syngeneic mice. It deals with those tumors that are immunogenic by virtue of their possession of tumor-specific, transplantation rejection antigens. A framework of evidence has been presented in the chapter that supports the hypothesis of down-regulation of antitumor immune response. Direct evidence for the hypothesis consists of the finding that infusion of suppressor spleen cells from donors with a large tumor can prevent recipient mice from generating a concomitant immune response. Additional direct evidence is being supplied by an ongoing study that shows that complete or partial regression of the Meth A fibrosarcoma that results from appropriately timed exposure to sublethal, whole-body γ-radiation is associated with a prolonged generation of effector T cells and an absence of suppressor T cells. It is suggested that down-regulation of antitumor immunity by suppressor T cells can explain the escape of only of those tumors that are immunogenic enough to evoke the generation of enough effectors T cells to cause tumor regression in the absence of suppressor T cells. This implies that the immunity generated to some tumors is too little too late to cause regression, even in the absence of the negative regulatory influence of suppressor cells. Therefore, successful immunotherapy of some established tumors, besides depending on the employment of agents capable of eliminating suppressor T cells, will also depend on the employment of agents capable of directly augmenting the generation of effectors T cells.

Transplantation of adrenal medullary tissue to striatum in parkinsonism. First clinical trials.

Abstract: ✓ Autologous adrenal medullary tissue was transplanted to the striatum in two patients with severe parkinsonism. The aim was to provide the striatum with a new cellular source of catecholamines. Some rewarding effects were registered. This is the first time that such tissue has been transplanted in the human brain. The results merit further clinical trials.

Role of liver transplantation in cancer therapy.

Abstract: Fifty-four patients underwent total hepatectomy and liver replacement in the presence of a primary liver malignancy. In 13 recipients in whom the hepatic tumors were incidental to some other endstage liver disease, recurrence was not seen and 12 of the 13 patients are alive after 4 months to 15 1/2 years. In contrast, tumors recurred in 3 of every 4 patients who received liver replacement primarily because of hepatic malignancies that could not be resected by conventional techniques of subtotal hepatectomy and who lived for at least 2 months after transplantation. The most encouraging results were in patients with the fibrolamellar hepatocellular carcinomas that grow slowly and metastasize late, but even with this lesion, the recurrence rate was 57%. In future trials, additional effective anticancer therapy will be needed to improve the results of liver transplantation for primary liver malignancy, but what an improved strategy should be has not yet been defined.

Epstein-Barr Virus Infections and DNA Hybridization Studies in Posttransplantation Lymphoma and Lymphoproliferative Lesions: The Role of Primary Infection

Abstract: Epstein-Barr virus (EBV) is a human herpesvirus associated with an array of conditions that range from inapparent infection and infectious mononucleosis to lethal lymphoproliferative syndromes, nasopharyngeal carcinoma, Burkitt’s lymphoma, and B cell lymphomas in immunocompromised patients [1]. The precise role of the virus in carcinogenesis is unclear, although in Burkitt’s lymphoma the importance of viral transformation of infected B lymphocytes and chromosomal translocations has been emphasized [2]. It is even less clear in lymphomas and lymphoproliferative lesions arising in immuno-compromised patients, where the immunopathology may not be uniform and where chromosomal studies are largely lacking. Recently, we reported on the reversibility of lymphomas and lymphoproliferative lesions in a series of 17 transplant patients after reduction of cyclosporine and steroid immunosuppression [3]. In that preliminary report we noted that seven of these patients had evidence of primary EBV infections and eight had evidence of reactivated infection. Six tumors had evidence of EBV nuclear antigen (EBNA) and seven had evidence of EBV DNA by nucleic acid hybridization. This paper examines in detail the relation between infection with EBV and the tumors in 14 of these 17 patients. The three patients who were excluded had their original transplants in Colorado (patients 1, 2, and 3 [3]). New data provided here include (1) frequency of EBV infection in the general transplant population; (2) additional serological studies in patients with tumors; (3) correlation of laboratory evidence of EBV infection and clinical illnesses accompanying the appearance of tumors; and (4) details of hybridization studies with highly specific and sensitive probes consisting of cloned fragments of the EBV genome. Calne et al. [4] and Thiru et al. [5] first observed three cases of lymphoma in 34 transplant patients receiving cyclosporine, of whom one had evidence of primary infection. Hanto et al. [6] reported the results of studies on 19 renal transplant patients who developed lymphoproliferative disorders and lymphomas after transplantation. All the patients except one were receiving azathioprine, prednisone, and antithymocyte globulin. Two of their patients developed primary EBV infection, in six the infection reactivated, and 12 had evidence of EBV DNA in their tumors by hybridization studies. Bieber et al. [7] reported that five of 39 heart transplant recipients receiving cyclosporine, prednisone, and antithymocyte globulin developed lymphomas. Four tumors were positive for EBV DNA by cRNA-DNA filter hybridization, and three patients had serological evidence of EBV infection. We report here evidence for active EBV infection in all of our patients with tumors and a significantly higher frequency of primary infection than found in control transplant recipients. Antibody responses to all EBV antigens and details of hybridization studies have not been reported in previous studies of patients with tumors.

Adenovirus Infections in Patients Undergoing Bone-Marrow Transplantation

Abstract: Viral infection is commonly observed after bone-marrow transplantation. We isolated adenovirus from 51 of 1051 patients undergoing marrow transplantation between 1976 and 1982. Of the 46 isolates available for typing, 13 (27.7 per cent) were of the closely related species 11, 34, or 35 (subgenus B). All 13 of the patients with these species had positive urine cultures. The species have previously been associated with the acquired immunodeficiency syndrome or with renal transplantation but are not commonly found in community surveys. Invasive infection was confirmed by biopsy or autopsy in 10 of 51 patients. Seven of the 10 had virus isolated from lung, and 4 died from pneumonia attributed to adenovirus. Two of the five patients with renal isolates had evidence of virally induced renal impairment, and both patients with liver isolates had adenovirus hepatitis. There was no common source that accounted for these adenovirus infections, and the most likely source of infection appeared to be endogenous viral reactivation. The only identifiable risk factor for the development of infection and for severe disease was the presence of moderate to severe graft versus host disease.

Epstein-Barr virus, immunodeficiency, and B cell lymphoproliferation.

Abstract: Revue: la biologie du virus; l'immunite vis-a-vis du virus; les receveurs de transplantation d'organe; les receveurs de greffe de moelle; le syndrome lymphoproliferatif lie a X(XLP), l'ataxie telangiectasie et les transplantations d'epithelium thymique; les modeles experimentaux

Infection with varicella- zoster virus after marrow transplantation

Abstract: Infection with varicella-zoster virus (VZV) occurred in 231 (16.6%) of 1,394 patients undergoing marrow transplantation in Seattle, Washington, between 1969 and 1982. The probability of VZV infection was 30% by one year after transplant. Eighty percent of infections occurred within the first nine months after transplant, and of these cases 45% had cutaneous or visceral dissemination. Twenty-three deaths were associated with VZV infection, all within the initial nine months after transplant. Postherpetic neuralgia, scarring, and bacterial superinfection were also significantly more frequent among patients with VZV in the first nine months after transplant (32%) than among patients with later infection (19%; P less than .05). By multivariate analysis, allogeneic transplant, acute or chronic graft-vs.-host disease, patient age between 10 and 29 years, diagnosis other than chronic myelogenous leukemia, and posttransplant use of antithymocyte globulin were each risk factors for VZV infection. Among infected patients, the only significant risk factor for VZV dissemination or death was acute graft-vs.-host disease (P less than .03 and P less than .0002, respectively.

The transplantation of an autogeneic osteochondral fragment for osteochondritis dissecans of the knee.

Abstract: Osteochondritis dissecans in two adults with a large osteochondral defect on the weight-bearing surface was treated by transplantation of an autogeneic osteochondral fragment. The graft was transplanted from the normal portion of the medial femoral condyle, which in extension was in contact with nei

Tricyclo compounds, a process for their production and a pharmaceutical composition containing the same

Abstract: This invention relates to tricyclo compounds useful for treatment and prevention of resistance by transplantation, graft-versus-host diseases by medulla ossium transplantation, autoimmune diseases, infectious diseases, and the like, which can be represented by the following formula: to a process for their production, to a pharmaceutical composition containing the same and to a use thereof.

Aspergillosis of the central nervous system: clinicopathological analysis of 17 patients.

Abstract: The clinical, laboratory, and pathological features of aspergillosis of the central nervous system (CNS) were studied in a series of 17 autopsied patients. Two groups were defined. Group A consisted of 8 patients with diseases commonly associated with CNS aspergillosis: leukemia, lymphoma, aplastic anemia, and renal transplantation. Group B contained 9 patients with various illnesses not generally known to be associated with CNS aspergillosis. CNS aspergillosis was diagnosed and treated before death in only 1 patient. Patients in Group A received cytotoxic drugs, often had granulocytopenia, less commonly had focal neurological deficits, and seldom had seizures. Group B patients were not granulocytopenic, received no cytotoxic agents, underwent nontransplant surgery, and more frequently had focal neurological deficits. Eleven of the 17 patients (65%) had focal deficits, most of them hemiparesis. Meningeal signs were rare, but the cerebrospinal fluid was usually abnormal. The principal neuropathological process was Aspergillus invasion of blood vessels causing hemorrhagic infarction. Focal clinical deficits correlated neuroanatomically with Aspergillus lesions. In 2 patients, such lesions were detected by 99mTc-DTPA or cerebral angiography before computed tomographic scanning. The lungs were the usual portal of entry, but isolated CNS lesions occurred in 2 patients. CNS aspergillosis should be considered as a cause of new onset of focal neurological deficits in patients with illnesses that are more diverse than has generally been appreciated.

Differentiation of Pulpal Cells and Inductive Influences of Various Matrices with Reference to Pulpal Wound Healing

Abstract: Based on recent literature, the dynamics of mesenchymal cells in transplantation of various tissues and matrices, as well as the origin of new odontoblasts which participate in the formation of the dentin bridge, are described. Experiments involving implantation of pulp, periosteum, perichondrium, treated dentin, and bone matrices were performed to emphasize the capability of these cells to produce hard tissue. Light and electron microscopic and autoradiographic studies were carried out to clarify the origin of replacement odontoblasts. It appears that the pulp cells, endothelial cells, and pericytes become undifferentiated mesenchymal cells following pulp exposure. These mesenchymal cells differentiate into odontoblasts, which subsequently produce a dentin matrix. Pulp tissues autografted to non-pulpal sites, elaborated bone (or osteodentin) matrix, but they did not graft to tubular dentin. An experiment on dentin bridge formation, using germ-free rats, demonstrated that the pulp tissue has intrinsic healing potential. Therefore, it was concluded that the ability of pulp tissue to elaborate hard tissues depends on its environment.

Substantia nigra transplants into denervated striatum of the rat: ultrastructure of graft and host interconnections.

Abstract: A number of recent experiments suggest that grafted dopaminergic neurons provide functional input to a host caudoputamen which previously had been deprived of its dopaminergic input. The purpose of the present study was to determine whether tyrosine hydroxylase immunoreactive processes which originate in the graft participate in morphologically identifiable synapses in the host neuropil. Prior to transplantation, adult Sprague-Dawley rats received unilateral injections of 6-hydroxydopamine into the medial forebrain bundle. Animals were screened for the success of striatal denervation by a test of apomorphine-induced rotation. Transplants of fetal substantia nigra then were placed into cavities in the caudoputamen. After a 6–8 month survival period, animals were perfused and prepared for tyrosine hydroxylase immunocytochemistry. No evidence of sprouting of the host catecholoaminergic system was observed, even after long survival times. Both pre- and postsynaptic immunoreactive elements were clearly present in the host caudoputamen. Immunoreactive axons made synaptic contact with unlabeled dendrites; immunoreactive dendrites were postsynaptic to unlabeled axon terminals. The present results suggest that both host-to-graft and graft-to-host synapses are present in the host caudoputamen.

Chronic implants of chromaffin tissue into the dopamine-denervated striatum. Effects of NGF on graft survival, fiber growth and rotational behavior

Abstract: Adult rat chromaffin tissue was transplanted into striatum of adult rat recipients whose nigrostriatal dopamine pathway had been lesioned on the grafted side by 6-hydroxydopamine. Long-term survival of the intrastriatal chromaffin grafts and the effects of treatment with nerve growth factor (NGF) was studied histochemically using Falck-Hillarp fluorescence histochemistry and functionally using rotational behavior induced by apomorphine. Small, cortex-free adrenal chromaffin tissue grafts survived permanently in striatum. The number of surviving cells was significantly increased by NGF. NGF treatment also caused transformation of many cells towards a more neuronal phenotype and greatly enhanced the adrenergic nerve fiber outgrowth into host brain tissue. NGF was either injected stereotaxically into the site of transplantation or infused continuously using implantable osmotic minipumps and a stereotaxically placed chronic indwelling dialysis fiber through striatum. The latter arrangement permitted continuous infusion of NGF for 14–28 days and caused a vigorous adrenergic nerve growth response by the grafts directed towards the source of NGF in the brain. There was a clearcut correlation between morphological signs of taking and rotational behavior. Grafts, and in particular grafts treated with NGF, were able to significantly and permanently counteract the rotational behavior induced by apomorphine. There seemed to be a dose relationship between NGF treatments and amount of reduction of asymmetric behavior. NGF treatment probably decreased the relative importance of diffuse release of catecholamines from chromaffin cells in the graft and increased the importance of adrenergic innervation of host striatum by cells in the graft. Immunofluorescence using antibodies against glial fibrillary acidic protein did not reveal any marked gliosis around the grafts nor were there any marked gliotic reactions around chronic indwelling dialysis fibers. We conclude that implantation of chromaffin tissue into striatum in conjunction with NGF treatments is an effective means of counteracting some of the symptoms of experimentally induced unilateral parkinsonism in rats.

Fungal infections in liver transplant recipients

Abstract: Sixty-two adults who underwent orthotopic liver transplantations between February 1981 and June 1983 were followed for a mean of 170 days after the operation. Twenty-six patients developed 30 episodes of significant fungal infection. Candida species and Torulopsis glabrata were responsible for 22 episodes and Aspergillus species for 6. Most fungal infections occurred in the first month after transplantation. In the first 8 weeks after transplantation, death occurred in 69% (18/26) of patients with fungal infection but in only 8% (3/36) of patients without fungal infection (P less than 0.0005). The cause of death, however, was usually multifactorial, and not solely due to the fungal infection. Fungal infections were associated with the following clinical factors: administration of preoperative steroids (P less than 0.05) and antibiotics (P less than 0.05), longer transplant operative time (P less than 0.02), longer posttransplant operative time (P less than 0.01), duration of antibiotic use after transplant surgery (P less than 0.001), and the number of steroid boluses administered to control rejection in the first 2 posttransplant months (P less than 0.01). Patients with primary biliary cirrhosis had fewer fungal infections than patients with other underlying liver diseases (P less than 0.05). A total of 41% (9/22) of Candida infections resolved, but all Aspergillus infections ended in death.

Suppression of Thyrotropin in the Low-Thyroxine State of Severe Nonthyroidal Illness

Abstract: In a prospective study, we assessed the role of thyrotropin in the development of the low-thyroxine state that is associated with severe illness. We measured the serum thyrotropin and thyroid hormone concentrations longitudinally in 35 patients with hematopoietic cancer or aplastic anemia who were treated by bone-marrow transplantation. In 19 patients thyroxine declined sharply after bone-marrow transplantation and was associated with a reduction of the serum thyrotropin in the 17 patients tested, often to levels below the normal range. The serum triiodothyronine level, free thyroxine index, and free thyroxine level also declined in these patients. In the patients who recovered, clinical improvement was accompanied by the return of thyrotropin and thyroid hormone concentrations to their pretreatment ranges. These and related findings suggest that the low-thyroxine state of severe illness is the result of several events, one of which is failure of the normal negative-feedback control of the pituit...

Circulating autologous stem cells collected in very early remission from acute non-lymphoblastic leukaemia produce prompt but incomplete haemopoietic reconstitution after high dose melphalan or supralethal chemoradiotherapy.

Abstract: Haemopoietic reconstitution (HR) using autologous peripheral blood stem cells (PBSC) was attempted after intensive chemotherapy or chemoradiotherapy in two patients with relapsed acute non-lymphoblastic leukaemia (ANLL). The PBSC were collected by leukapheresis very early in first remission and cryopreserved in liquid nitrogen. Both patients demonstrated early evidence of trilineage engraftment. The first patient received melphalan 200 mg/m2 followed by rescue with 1.3 X 10(8) mononuclear cells/kg body weight containing 29 X 10(4) granulocyte-macrophage progenitor cells (CFU-GM)/kg, and HR was evident by Day 14. The second patient was treated with supralethal chemoradiotherapy followed by rescue with 3.0 X 10(8) mononuclear cells/kg containing 23 X 10(4) CFU-GM/kg. He demonstrated early engraftment with near normal peripheral blood counts by Day 16. There was a subsequent fall in both bone marrow cellularity and peripheral blood counts to a level of low but persistent activity. There was a further phase of haematological recovery from 8 weeks following transplantation with an increase in peripheral blood counts and bone marrow cellularity until final relapse at 13 weeks. This study demonstrates that circulating stem cells have haemopoietic reconstitutive capacity, previously only shown with buffy coat cells from chronic granulocytic leukaemia. The minimum number of PBSC required for satisfactory engraftment remains unknown, although it seems probable that the ratio of pluripotent stem cells to committed progenitor cells is lower in very early remission peripheral blood than in either allogeneic normal bone marrow or autologous bone marrow collected later in stable remission. The question of leukaemic contamination of the PBSC remains to be answered.

Prevention of type I diabetes in nonobese diabetic mice by allogenic bone marrow transplantation

Abstract: An animal model [the nonobese diabetic (NOD) mouse] for type I diabetes features a striking infiltration of T cells into the pancreatic islets This infiltration selectively destroys beta cells Most of the T cells are Lyt-1+, but some are Lyt-2+,3+ Transfer experiments using parabiosis revealed that insulitis can be transferred within 2 weeks after parabiosis to immunoincompetent thymectomized mice When NOD mice (6 mo old) were irradiated and reconstituted with bone marrow cells from young BALB/c nu/nu mice (less than 2 mo old), the NOD mice exhibited neither insulitis nor overt diabetes Deposits of immunoglobulin in mesangial areas of the glomeruli disappeared within 3 mo after bone marrow transplantation in such irradiated allogeneic bone marrow reconstituted mice Assays for immunological functions, including mitogen response and mixed lymphocyte reaction, revealed that both T- and B-cell functions were increased in NOD mice with overt diabetes NOD mice reconstituted with BALB/c nu/nu bone marrow cells displayed normal T- and B-cell functions The newly developed T cells in the allogeneic bone marrow recipients are tolerant to cells with both donor- and host-type major histocompatibility complex determinants These results suggest that bone marrow transplantation may ultimately be developed as a component of a strategy to be employed for treatment of type I diabetes in humans

Rationale for bone marrow transplantation in the treatment of autoimmune diseases.

Abstract: Transplantation of normal bone marrow from C3H/HeN nu/nu (H-2k) mice into young MRL/MP-lpr/lpr (MRL/l; H-2k) mice (less than 1.5 mo) prevented the development of autoimmune diseases and characteristic thymic abnormalities in the recipient mice. When female MRL/1 (greater than 2 mo) or male BXSB (H-2b) mice (9 mo) with autoimmune diseases and lymphadenopathy were lethally irradiated and then reconstituted with allogeneic bone marrow cells from young BALB/c nu/nu (H-2d) mice (less than 2 mo), the recipients survived for more than 3 mo after the bone marrow transplantation and showed no graft-versus-host reaction. Histopathological study revealed that lymphadenopathy disappeared and that all evidence of autoimmune disease either was prevented from developing or was completely corrected even after its development in such mice. All abnormal T-cell functions were restored to normal. The newly developed T cells were found to be tolerant of both bone marrow donor-type (BALB/c) and host-type (MRL/1 or BXSB) major histocompatibility complex (MHC) determinants. Therefore, T-cell dysfunction in autoimmune-prone mice can be associated with both the involutionary changes that occur in the thymus of the autoimmune-prone mice and also to abnormalities that reside in the stem cells. However, normal stem cells from BALB/c nu/nu donors can differentiate into normal functional T cells even in mice whose thymus had undergone considerable involution, as in the case of BXSB or MRL/1 mice in the present studies. These findings suggest that marrow transplantation may be a strategy ultimately to be considered as an approach to treatment of life-threatening autoimmune diseases in humans. T-cell dysfunction in autoimmune-prone mice previously attributed to involutionary changes that occur in the thymus of these mice may instead be attributed to abnormalities that basically reside in the stem cells of the autoimmune-prone mice.