Showing papers on "Transplantation published in 1981"

Acyclovir Prophylaxis of Herpes-Simplex-Virus Infections

Abstract: We conducted a double-blind, placebo-controlled study of acyclovir prophylaxis against infection with herpes simplex virus (HSV) in 20 seropositive recipients of bone-marrow transplants. Acyclovir or placebo was administered for 18 days, starting three days before transplantation. Culture-positive HSV lesions developed during the study in seven of the 10 patients who received placebo. In contrast, no such lesions appeared in the 10 patients who received acyclovir (P congruent to 0.003). None of the patients had evidence of drug toxicity. Five of the patients treated with acyclovir had mild culture-positive HSV infections after cessation of the drug, and two additional patients shed virus without having lesions. Acyclovir appears to be a potent inhibitor of HSV replication. Although acyclovir does no appear to eradicate latent infection, it can provide effective prophylaxis against reactivated infections.

Liver transplantation with use of cyclosporin a and prednisone.

Abstract: THE difficulties in consistently prolonging survival after orthotopic liver transplantation have been documented by us1 and by Calne.2 In this report we describe a new trial of orthotopic liver tra...

Clinical Spectrum of Lymphoproliferative Disorders in Renal Transplant Recipients and Evidence for the Role of Epstein-Barr Virus

Abstract: Six renal transplant recipients with abnormal lymphoproliferative disorders were studied in an attempt to define their clinical features and the role of Epstein-Barr virus (EBV) in their pathogenesis. Patients were either teenage (three) or in the sixth decade (three). The younger patients presented an average of 3 months after transplantation with fever, sore throat, and lymphadenopathy; had been markedly immunosuppressed; frequently had preceding or concomitant cytomegalovirus infections; and two of three had a rapidly fatal course. The older patients presented an average of 5 years after transplantation while on maintenance immunosuppressive drugs; in two of three cases with an oropharyngeal tumor; and had a more indolent, but frequently fatal, clinical course. The most frequent sites of biopsy-proven involvement in these patients were lymph nodes (three), the oropharynx (three), liver (three), bone marrow (three), transplanted kidney (three), colon (two), and central nervous system (two). EBV-specific antibody titers including anti-viral capsid antigen IgG, anti-viral capsid antigen IgM, anti-early antigen, and anti-Epstein-Barr nuclear antigen were serially measured in all patients. Four patients demonstrated serological evidence of a primary (one) or reactivation (three) EBV infection. No patient had significant changes in anti-early antigen or anti-Epstein-Barr nuclear antigen titers. All three patients tested for oropharyngeal shedding of EBV were positive. A touch imprint of one tumor was stained for the presence of Epstein-Barr nuclear antigen, and a majority of cells were positive. EBV complementary RNA/DNA filter hybridization and/or viral DNA/DNA reassociation analysis performed on tumor biopsy specimens in five patients demonstrated multiple EBV genome equivalents per cell in all eight specimens tested. Clinical, pathological, serological, and molecular hybridization studies provide substantial evidence that EBV was the cause of these lymphoproliferative disorders occurring after renal transplantation. Impaired host defenses allow the EBV-transformed B-lymphocytes to escape normal control mechanisms. This impairment is variable and influenced by many factors resulting in the observed spectrum of disease. Cytogenetic changes, however, may also be important.

Habitat Partitioning and Competitive Displacement in Cattails (Typha): Experimental Field Studies

Abstract: The aquatic plants Typha latifolia and T. angustifolia are observed to be strongly segregated along a gradient of increasing water depth with T. latifolia restricted to depths of less than 80 cm and T. angustifolia to depths greater than 15 cm. Transplantation of both species along the gradient in the absence of competitors showed that T. latifolia was little affected by the presence of T. angustifolia but T. angustifolia was capable of growing over the entire gradient. The loss of precompetitive distribution was not statistically significant for T. latifolia compared to a 39.6% loss for T. angustifolia. It was further observed that overlap was reduced by 43.5% during the course of the growing season. Rhizomes transplanted into natural stands failed to survive, further demonstrating that competition was actively operating to maintain zonation between species. The basis for habitat partitioning appears to be a difference in morphology whereby T. latifolia was prevented from growing in deep water because of...

Treatment of acute renal allograft rejection with okt3 monoclonal antibody

Abstract: Eight cadaver donor renal allograft recipients, who had received azathioprine and prednisone from the day of transplantation, were treated with OKT3 monoclonal antibody (reactive with all mature peripheral blood T cells) at the time of diagnosis of acute rejection. In all cases, loss of essentially all detectable peripheral blood OKT3-reactive cells was noted within minutes after the initial 1- to 5-mg i.v. infusion. Chills and fever invariably occurred following the first or second infusion of monoclonal antibody, but were not noted during the subsequent, 10- to 20-day course of therapy, suggesting rapid cell lysis as the etiology of this toxicity. The established rejection episode was reversed in all cases within 2 to 7 days without addition of any therapy other than OKT3 antibody and despite continued lowering of the steroid dosages. During the subsequent 3- to 12-month follow-up period, further rejection episodes occurred in five of these patients, two of these were irreversible with conventional therapy so that six of the eight allografts continue with excellent renal function. These preliminary observations suggest that homogeneity, limited dosage requirements, and ease of in vitro monitoring of dosage effects should markedly simplify the use of monoclonal antibody to T cell populations in human allograft recipients. This second generation of antilymphocyte preparations offers the potential for not only increased effectiveness but also the possibility of manipulating specific T cell subsets.

Influences of the glial environment on the elongation of axons after injury: transplantation studies in adult rodents

Abstract: Tissue transplantation methods, previously used to study neural development, myelination and inherited disorders of myelin can be applied also to the investigation of repair and regeneration in the mammalian CNS. The elongation of axons from injured peripheral nerve of CNS has been studied in adult mice and rats by observing the growth of axons into PNS or CNS tissue grafts. Following spinal cord injury and also after transplantation of optic nerves into the PNS there is axonal sprouting but these neuronal processes fail to elongate more than a few mm into the surrounding glia. On the other hand if segments of a peripheral nerve are grafted into the transected spinal cord, axons arising from spinal neurons and dorsal root ganglia become associated with the transplanted Schwann cells and elongate along the graft, approximately 1 cm. Recently the elongation of axons from spinal and medullary neurones was studied using a new experimental model which employed PNS grafts as 'bridges' to connect the spinal cord and the brain stem. In a series of adult C57BL/6J mice and Sprague Dawley rats, autologous segments of sciatic nerve were used to create 'bridges' between the lower cervical or upper thoracic spinal cord and the medulla oblongata. The spinal cord between these two levels was left intact. Grafted segments examined by light and electron microscope 1-7 months after surgery were well innervated by Schwann cell ensheathed axons that had grown the entire length of the graft (2 cm in mice and 3.5 cm in rats). The origin and termination of these axons were determined by transecting the regenerated grafts and applying horseradish peroxidase to the cut ends. Retrogradely labelled neurones were found to be distributed widely in the gray matter of the spinal cord and medulla near the sites of insertion of the graft. Anterogradely labelled fibres coursing within the graft penetrated the CNS for short distances, approximately 2 mm. These new results indicate that following CNS injury a conducive glial environment does allow spinal and brain stem neurones to elongate axons for distances that can be greater than those they usually extend for in the intact animal. This evidence that the regenerative response of similar axons differs in CNS and PNS neuroglia supports the hypothesis that influences arising from the environment play an important role in the success or failure of regeneration. The regenerative potentiality of central neurones may be expressed only when the CNS neuroglial environment is changed to resemble that in the PNS.

Efforts to explain spontaneous regression of cancer

Abstract: After a study of the 176 cases (Everson and Cole) of spontaneous regression of cancer and recent progress in immunology, the author is convinced stimulation of the immune process is the most important factor in S.R. of cancer. Stimulating factors are numerous including bacterial products, enzymes, infections, hormones, trauma, etc. Of the 176 cases reported by Everson and Cole, 71 (40%) were associated with some type of operative trauma. Since the effective anticancer agent interferon is an important protective agent (especially antiviral) in the human body, this product could readily play an important role. Immunoglobulins appear to be possible factors. The blocking and unblocking agents of the Hellstroms and associates support this supposition. Elimination of carcinogens appears important, considering the remarkable disappearance of cancer of the bladder in 12 of 13 patients having diversion of the urine from the bladder to the colon by transplantation of the ureters from the bladder to the colon. Innumerable antigens unknown to us at the present time could act as stimulants to our immune system, and thus cause regression of cancer. Hormonal factors must obviously be considered, but the author is doubtful that they exert an important role.

Reversal of transplantation immunity by liver grafting

Abstract: The transplantation of organs between individuals of a species normally has two main consequences: (1) the tissue is rejected unless the individuals are matched for identity of transplantation antigens, especially those encoded by the major histocompatibility complex (MHC), and (2) the recipient is sensitized to the transplantation antigens of the donor so that second-set grafts are rejected in a more violent manner1. These rules of transplantation are not obeyed by liver grafts. Orthotopic transplants of liver are never rejected by many strains of rat even though the MHC barrier is crossed2. We have recently shown that instead of sensitizing the recipient, these enduring liver grafts induce a state of donor-specific unresponsiveness in which subsequent grafts of other organs, such as skin, are accepted permanently. It is possible that many strains simply cannot mount a sufficiently vigorous destructive immune response to outstrip the liver's great capacity to repair immune damage and that the systemic unresponsiveness observed is due to diversion of alloreactive lymphocytes with donor specificity into the liver allograft. Manipulations which increase the vigour of the immune response might therefore tip the balance in favour of liver graft rejection and away from induction of unresponsiveness. We have previously measured the degree to which the immune response can be increased by previous exposure to MHC antigens in a quantitative adoptive transfer system3. In the strain combination DA (MHC haplotype RT-1a) grafted to PVG (RT-1c), the lymphocytes of immunized animals are 1,000 times more potent than those of non-immune animals in procuring graft destruction when transferred to irradiated hosts. Unexpectedly, we have now found that liver grafts transplanted into previously immunized rats not only fail to reject but convert the state of heightened reactivity to donor grafts characteristic of immune recipients into one of non-reactivity characteristic of tolerant animals.

Glomerulopathy Associated with Cytomegalovirus Viremia in Renal Allografts

Abstract: We investigated the relation between cytomegalovirus (CMV) infection and renal-allograft dysfunction in 14 patients. In seven instances (including two successive transplants in one patient), allograft dysfunction occurred during clinically manifest, viremic CMV infection. In five of these, biopsies revealed little or no tubulointerstitial change but a distinctive, diffuse glomerulopathy characterized by enlargement or necrosis of endothelial cells and accumulation of mononuclear cells and fibrillar material in glomerular capillaries. Two of these allografts recovered their function, both with cessation of high-dose immunosuppression. Biopsies in the other 10 patients revealed predominantly tubulointerstitial changes typical of cellular rejection, and most of these patients did not have viremia. One additional patient, studied prospectively, manifested both forms of allograft injury: tubulointerstitial changes occurring two weeks after transplantation and responding to increased immunosuppression,...

Cytomegalovirus infections following renal transplantation.

Abstract: This collective review of the literature concerns posttransplantation cytomegalovirus (CMV) infections. In the author's view, patients without previous CMV infection are most often infected by viruses transmitted with the transplanted kidney, whereas patients with prior infections can be infected either from this source or by reactivation of latent CMV. Many posttransplantation CMV infections are asymptomatic or yield only mild systemic effects. A few patients suffer life-threatening disease. However, CMV infections might adversely affect survival of both graft and patient by contributing to graft rejection, weakening the graft recipient's immunity, or by other, more indirect, means. Currently, there is no effective, specific treatment of these infections. It is predicted that CMV infections will cease to be a problem only when the means are found to specifically block transplantation immunity, thereby eliminating the need for systemic immunosuppression and eliminating low-level host-vs.-graft responses.

Spleen colony-forming cell as common precursor for tissue mast cells and granulocytes

Abstract: The haematopoietic stem cells which produce colonies in the spleen of irradiated mice (CFU-S) can differentiate into erythrocytes, granulocytes, megakaryocytes and B lymphocytes. Although mast cell precursors are known to be present in the bone marrow, spleen, fetal liver and peripheral blood of mice, the relationship between the mast cell precursor and CFU-S has remained unclear. We have now made use of mice of two mutant genotypes to determine whether or not the tissue mast cell is a progeny of CFU-S. Giant granules of beige (C57BL/6-bg/bg, Chediak-Higashi syndrome) mice can be used for identification of the origin of both tissue mast cells and granulocytes, and WBB6F1-W/Wv mice are useful recipients because they lack tissue mast cells owing to a defect in mast cell precursors. We injected the cells from a single spleen colony into each WBB6F1-W/Wv mouse and demonstrated directly that the tissue mast cell is a progeny of CFU-S.

A Comparison of Marrow Transplantation with Chemotherapy for Children with Acute Lymphoblastic Leukemia in Second or Subsequent Remission

Abstract: The progress of 24 children with acute lymphoblastic leukemia treated with cyclophosphamide, total-body irradiation, and marrow transplantation during a second or subsequent remission was compared with that of 21 children treated with conventional chemotherapy after they had entered a second remission. Eleven of the transplantation group are alive, including nine in continuing complete remission for 17 to 55 months; only two of the chemotherapy group are alive, one in complete remission after 20 months. Relapse was the major cause of failure in both groups. Acute and chronic graft-versus-host disease in the transplantation group and leukoencephalopathy in both groups were the other major causes of morbidity and mortality. This study demonstrates that marrow transplantation currently offers the best chance of long-term remission and potential cure after a child with acute lymphoblastic leukemia has had a relapse in the marrow. (N Engl J Med. 1981; 305:846–51.)

Prolongation of murine islet allograft survival by pretreatment of islets with antibody directed to Ia determinants

Abstract: Islets of Langerhans treated with donor-specific anti-Ia serum and complement were transplanted across a major histocompatibility barrier into nonimmunosuppressed diabetic mice. The allografts survived in all recipients for at least 200 days after transplantation. Rejection of an established allograft could be induced by intravenous injection of donor splenocytes. This demonstrates that allografts can serve as targets for immune rejection and supports the possible role of Ia-positive passenger lymphoid cells in initiation of immune rejection. The results show that immunosuppression of the recipient is not a prerequisite for successful transplantation.

Microvascular management of ring avulsion injuries

Abstract: Microsurgical revascularization has proved to be a useful method in managing the ring avulsion injury where both neurovascular bundles are damaged with only partial skin avulsion. Representative cases are used to illustrate guidelines for a practical classification for helping to decide the optimal method of treatment of acute ring avulsion injuries in light of digital revascularization techniques. Nine ring fingers were successfully revascularized of 24 acute ring avulsion injuries reviewed. Sensibility recovery was good and a functional range of motion obtained. No patient who has had his ring finger revascularized has requested its amputation because of appearance, painful neuromas, stiffness, or cold intolerance. Complete amputations, especially proximal to the superficialis insertion, and complete degloving injuries of the ring finger are usually best managed by surgical amputation of the digit.

Surgical therapy for persistent hypertension after renal transplantation.

Abstract: SUMMARY The presence of the original diseased native kidneys in renal allograft recipients is associated with an increased prevalence of persisting post-transplant hypertension. In 9 of 10 such transplant patients bilateral nephrectomy of these native kidneys, performed at least 1 year after successful transplantation of a renal allograft, resulted in improved blood pressure control. Although these 10 patients had higher peripheral plasma renin activity (PRA) than normotensive patients (5.9 ± 1.3 ng/ml/hr versus 1.5 ± 0.3 mg/ml/hr), selective renal vein renin measurements did not consistently demonstrate higher renin concentrations from the native kidneys. Removal of the original kidneys was beneficial even in some patients who had stenosis of the allograft artery demonstrated by arteriography.

Nocardial Infections in the Immunocompromised Host: A Detailed Study in a Defined Population

Abstract: A retrospective, clinical, epidemiologic, and risk-factor analysis was performed on 21 recipients of cardiac allografts who had experienced nocardiosis since the inception of the cardiac transplantation program at Stanford University Medical Center in 1968. The lung was the primary and only detectable site of infection in 17 (81%) of 21 patients, and there were three cases of disseminated disease. Presenting symptoms were either nonspecific (dry cough and fever) or absent (in 40%). The time of onset of infection following transplantation was variable (range, 43-982 days), and there was no period of peak incidence. Epidemiologic and risk-factor analysis failed to identify a nosocomial point-source or specific parameters that predisposed a patient to nocardial infection. Nocardiosis was not associated with the onset of primary infection with cytomegalovirus following transplantation. However, an association between pulmonary nocardiosis and subsequent development of nontuberculous mycobacteriosis was established in five of the 21 patients. All patients with nocardiosis were treated primarily with sulfisoxazole (6-12 g per day) for a mean of 13.2 months. No deaths were attributable to nocardial infection, nor could acquisition of the infection be shown to affect overall survival. The results of the study support an aggressive approach to diagnosis of infections in the immunocompromised host and suggest that a favorable therapeutic outcome may be anticipated in such individuals who sustain nocardiosis if the diagnosis is made early in the course of the infection and if appropriate antimicrobial therapy is instituted.