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Biomedical subjects

D W Hanto

Publications and source records attributed to D W Hanto.

At least 55 records · Page 3Linked to original sources
PubMed1990

Fulminant hepatic failure caused by acute fatty liver of pregnancy treated by orthotopic liver transplantation.

A previously healthy 35-year-old woman was seen at 37 weeks' gestation with a 10-day history of fever, vomiting, diarrhea and malaise. Serum laboratory findings included elevation of serum bilirubin and AST, prolongation of serum prothrombin time and a positive monospot. A tentative diagnosis of acute fatty liver of pregnancy was made, and a healthy male infant was delivered by emergency cesarean section because of fetal distress. Over the subsequent 3 days, acute progressive oliguric renal failure, disseminated intravascular coagulation, hypoglycemia requiring intravenous dextrose infusion and pancreatitis developed; her mental status progressed to stage III encephalopathy. Quantitative computed tomography estimated the liver volume to be 770 cm3. The decision to proceed with orthotopic liver transplantation was made on the basis of progressive clinical deterioration despite aggressive support and because of her small liver size. After transplant, the patient's multisystem failure rapidly reversed. Histopathological examination of the native liver demonstrated predominantly zone 3 microvesicular steatosis with characteristic ultrastructural changes consistent with acute fatty liver of pregnancy. Southern blot analysis for Epstein-Barr virus DNA was negative. We conclude that orthotopic liver transplantation should be considered for the small group of patients with fulminant hepatic failure associated with acute fatty liver of pregnancy who manifest signs of irreversible liver failure despite delivery of the fetus and aggresive supportive care.

Acute Disease↗
PubMed1990

Immunoblastic lymphoma of T-cell type in a chronically immunosuppressed renal transplant recipient.

A case of non-Hodgkin's lymphoma of T-cell type occurring in a renal transplant recipient is described. This lymphoma was classified as large cell, immunoblastic type and presented as a mediastinal mass, although it was demonstrated to be disseminated at autopsy two weeks later. Lymphoma cells expressed the immunologic profile of a mature, activated cytotoxic/suppressor T-lymphocyte. T-cell receptor gene rearrangement and karyotypic studies confirmed a clonal T-cell genotype. Molecular studies failed to demonstrate any association with Epstein-Barr virus or human T-cell lymphotropic virus type I or type II. Pathogenesis of lymphomas in this clinical setting is discussed.

Adult↗
PubMed1990

Comparison of culture and serology for the diagnosis of cytomegalovirus infection in kidney and liver transplant recipients.

This study compared culture, including the shell vial procedure, with serology, including IgM cytomegalovirus (CMV) antibody testing, for the diagnosis of CMV infection in 42 subjects undergoing cadaveric renal or liver transplantation. Of 35 subjects who developed active CMV infection, 31 had positive cultures, while IgM CMV antibodies were detected in 29. Subjects with symptomatic CMV infection were more likely than asymptomatic subjects to have positive cultures of leukocytes (17/18 vs. 9/17, P = .01). In contrast, symptomatic and asymptomatic subjects did not differ in their IgG or IgM CMV antibody test responses. In subjects with symptomatic infection, viral shedding typically began early in the course of infection, often preceding symptoms, while the serologic response usually followed the appearance of symptoms. With the use of the shell vial procedure to facilitate detection of positive cultures, symptomatic CMV infections following kidney or liver transplantation can be recognized earlier and more reliably using viral culture than by serologic testing.

Adult↗
PubMed1989

Confirmation of the heterogeneity of posttransplant Epstein-Barr virus-associated B cell proliferations by immunoglobulin gene rearrangement analyses.

Immunoglobulin gene rearrangement analysis is a sensitive method for determining clonality of B cell proliferations. We have examined tissue obtained from five renal and one cardiac allograft recipient with Epstein-Barr virus-associated B cell proliferations for immunoglobulin gene rearrangements. Biopsies from two patients with lesions that were hyperplastic morphologically, polyclonal by cellular immunoglobulin staining, and had diploid karyotypes, had no detectable gene rearrangements and were, therefore, consistent with benign reactive processes. These patients are alive without evidence of disease 37 and 57 months after diagnosis. In a biopsy from one patient with a lesion that was malignant lymphoma morphologically, monoclonal by cellular immunoglobulin staining, and had clonal cytogenetic abnormalities, clonal gene rearrangements were detected in a majority of cells, confirming their neoplastic nature. In biopsies from an intermediate group of three patients with morphologically malignant proliferations that were composed predominantly of a polyclonal population of B cells, clonal gene rearrangements were also found, consistent with early malignant transformation in a subpopulation of cells. These findings confirm the heterogeneity of the posttransplant EBV-associated lymphoproliferative diseases and have significant implications for our understanding of the pathogenesis of EBV-induced infections and related lymphomas.

Adolescent↗
PubMed1989

Concomitant immunosuppression and donor-specific transfusions prior to renal transplantation.

The induction of immunologic unresponsiveness to improve renal allograft survival was attempted in 151 patients by the pretransplant administration of donor-specific whole blood or buffy coat in conjunction with continuous Aza immunosuppression. All donor-recipient combinations were at least one-haplotype disparate and 21 were two-haplotype disparate. Presensitization was present in ten patients and attempts at desensitization were uniformly unsuccessful. Of the 151 nonpresensitized patients, transient sensitization occurred in 3% and permanent sensitization in 7%. Of 140 nonsensitized patients, 135 underwent renal transplantation from the specific blood donor and 56% have never experienced a rejection episode. The allograft survival rate at two years (93%) and seven years (87%) is significantly better (p less than .01) than our historical experience with one-haplotype living-related transplants at two years (68%) and seven years (59%). The low rate of sensitization (7%) has permitted almost all patients to undergo eventual renal transplantation from the specific blood donor. This and the low rate of early rejection (2%) argues for a modification of the immunologic response, perhaps by clonal deletion, rather than a selecting out process as the mechanism for improved allograft survival.

Azathioprine↗
PubMed1988

Lack of an obligate role for IFN-gamma in the primary in vitro mixed lymphocyte response.

We have investigated the relative importance of two lymphokines, IL-2 and IFN-gamma, in the primary murine MLR. Three separate lines of evidence indicate that IL-2 and not IFN-gamma is the relevant lymphokine for both proliferation and activation of CTL in these cultures. No obligate role for IFN-gamma was found. First, CTL activation in the presence of high dose cyclosporin A was partially reconstituted with IL-2, although no detectable IFN-gamma was produced in such cultures. In addition, IFN-gamma could not reconstitute cyclosporin-inhibited cultures. Second, inclusion of a high concentration of several distinct anti-IFN-gamma antibodies failed to inhibit MLR cultures. Third, CTL activation by stimulator cells inactivated by UV irradiation was reconstituted by IL-2, but not by IFN-gamma. These data do not support an autocrine role of IFN-gamma in CTL activation and confirm the importance of IL-2 in the primary murine MLR.

Animals↗
PubMed1988

Renal allograft recipient immunomodulation by concomitant immunosuppression and donor-specific transfusions.

The induction of immunologic unresponsiveness to improve renal allograft survival was attempted in 151 patients by the pretransplant administration of donor-specific whole blood or buffy coat in conjunction with continuous Aza immunosuppression. All donor-recipient combinations were at least one-haplotype disparate and 21 were two-haplotype disparate. Presensitization was present in ten patients and attempts at desensitization were uniformly unsuccessful. Of the 151 nonpresensitized patients, transient sensitization occurred in 3% and permanent sensitization in 7%. One hundred thirty-five of 140 nonsensitized patients underwent renal transplantation from the specific blood donor and 56% have never experienced a rejection episode. The allograft survival rate at 2 years (93%) and 7 years (87%) is significantly better (P less than .01) than our historical experience with one-haplotype living-related transplants at 2 years (68%) and 7 years (59%). The low rate of sensitization (7%) has permitted almost all patients to undergo eventual renal transplantation from the specific blood donor. This and the low rate of early rejection (2%) argue for a modification of the immunologic response, perhaps by clonal deletion, rather than a selecting-out process as the mechanism for improved allograft survival.

Azathioprine↗
PubMed1987

Renal transplantation: clinical considerations.

Renal transplantation is the treatment of choice for adults and children with end-stage renal disease. More than 7500 kidney transplants are performed in the United States each year with an average 2-year graft survival rate of 95, 85, and 75 per cent for HLA-identical, living related, and cadaver donor recipients, respectively. New immunosuppressive modalities including donor specific transfusions and cyclosporine have resulted in improved results with fewer infectious complications. Careful attention to hemostasis, minimization of tissue injury, and aseptic technique is necessary in uremic and immunosuppressed patients. The most common complications requiring radiologic evaluation and treatment after renal transplantation include acute tubular necrosis, renal artery or renal vein thrombosis, lymphocele, ureteral necrosis, bladder disruption, bleeding, ureteral obstruction or stricture, and renal artery stenosis. The most useful radiologic studies are renograms, echograms, computed axial tomograms, cystograms, arteriograms, percutaneous nephrostograms, and intravenous or retrograde pyelograms.

Adult↗
PubMed1987

Pancreas transplantation: clinical considerations.

The number of pancreas transplants performed and the success rate have increased significantly since the first segmental pancreas transplant was performed in 1966. Since 1977, 716 pancreas transplants have been performed in 670 patients at 69 institutions. Currently 230 grafts (32 per cent) are listed as functioning (insulin independent). The present 1-year actuarial graft and survival rates at the University of Minnesota are 43 and 88 per cent, respectively. The indications for pancreas transplantation and the selection of recipients have undergone modification, and more nonuremic nonkidney transplant patients are now receiving pancreas allografts. A variety of techniques have been used for pancreas transplantation. Whole or segmental pancreas grafts have been used. Most centers drain the graft exocrine secretions into the gastrointestinal tract as a Roux-en-Y pancreaticojejunostomy or into the bladder as a pancreaticocystostomy. The most common complications requiring radiologic evaluation and treatment include vascular thromboses utilizing technetium flow studies and arteriography and intra-abdominal fluid collections and infections requiring ultrasonography and CT scans. Percutaneous aspiration of intra-abdominal fluid collections is important for diagnosis but has not been successful therapeutically. Intra-abdominal infections are most common in patients with enteric drainage of the pancreas graft, which carries a high risk of contamination at the site of anastomosis. Most intra-abdominal infections require surgical drainage and removal of the graft.

Cadaver↗
PubMed1986

Mediation of cellular recruitment in vivo by functionally distinct T cell clones.

The ability of functionally distinct alloreactive T cell clones to mediate cellular recruitment in vivo was examined in a modified sponge matrix allograft model. Changes in cellular recruitment to paired healed s.c. urethane sponge grafts injected with cytolytic T lymphocyte (CTL), helper, or helper-independent CTL clones, or bulk resting mixed leukocyte culture (MLC) cells, and allogeneic or syngeneic blasts were studied. Injection of indium-111-labeled unsensitized cells i.v. was used to assess cellular recruitment to the graft site. All three alloreactive T cell clones and bulk MLC cells mediated preferential recruitment of circulating labeled cells when injected with allogeneic cells. The helper clone mediated significantly greater recruitment than the CTL clone. These results confirm at the clonal level our previous observations that populations of allosensitized cells enriched for either cytolytic or noncytolytic T lymphocytes can mediate cellular recruitment in vivo and extends them to include helper-cell-independent cytolytic T lymphocytes.

Animals↗
PubMed1986

Evidence that secondary mixed leukocyte culture supernatant mediates changes in cellular recruitment, blood flow, and vascular permeability.

Lymphokines produced as a result of allostimulation may play an important role in allograft rejection, mediating changes in cellular infiltration and migration, regional blood flow, and vascular permeability in a manner similar to that of delayed type hypersensitivity reactions. Changes in cellular recruitment (CR), regional blood flow (RBF), and vascular permeability (VP) were studied in paired healed subcutaneous urethane sponge grafts inoculated with secondary mixed leukocyte culture supernatant (2 degrees MLC SN), a rich source of a variety of lymphokines secreted in response to allostimulation. Intravenous injection of Indium-111-labeled unsensitized lymphocytes (UL), Rubidium-86-chloride, and Iodine-125-labeled albumin were used to assess CR, RBF, and VP, respectively. An increase in CR (P less than 0.001), RBF (P less than 0.05), and VP (P less than 0.001) could be demonstrated at the site of injection of allogeneically restimulated 2 degrees MLC SN compared with the syngeneically restimulated 2 degrees MLC SN. The quantitative response and the kinetics of CR using 2 degrees MLC SN were similar to previous studies in which specifically sensitized lymphocytes were injected with target cells bearing the sensitizing alloantigen, but the increase in RBF and VP were less. Injection of purified human interleukin, 2 serotonin, histamine, and bradykinin had no significant effect on CR. Injection of purified human interleukin 1 resulted in a moderate increase in CR. These results are consistent with previous studies suggesting that the in vivo elaboration of lymphokines during allogeneic cellular interactions leads to an increase in CR, RBF, and VP. The small changes in RBF and VP in these experiments, however, do not account for the greater magnitude of the changes in CR. It is likely that other specific or nonspecific chemoattractants or inhibitors of cell migration also play a significant role in CR in vivo.

Animals↗
PubMed1985

Advances in the diagnosis and treatment of EBV-associated lymphoproliferative diseases in immunocompromised hosts.

The clinical, immunopathologic, and virologic features of the lymphoproliferative diseases occurring after renal transplantation have been characterized. Clinically, patients may present with an infectious mononucleosis-like illness or with localized solid tumor masses. These lymphoproliferative diseases have unique histologic features that can be classified as polymorphic diffuse B-cell hyperplasia (PDBH) or polymorphic B-cell lymphoma (PBL). Immunologic cell-typing studies have shown that the majority are polyclonal B-cell proliferations, but monoclonal B-cell tumors have also been documented. These B-cell proliferations may, however, evolve from a benign polyclonal B-cell hyperplasia to a monoclonal malignant lymphoma. The Epstein-Barr virus (EBV) has been implicated as the cause of these disorders. Serologic studies frequently demonstrate evidence of a primary or reactivation infection, touch imprints from involved tissue may stain for the presence of EBNA (Epstein-Barr nuclear antigen), and EBV DNA hybridization studies demonstrate the presence of EBV-specific DNA sequences within tumor cells. Since EBV induces a polyclonal B-cell proliferation in vitro and in vivo, the polyclonality of these diseases also implicates EBV. Acyclovir, a new synthetic antiviral agent that inhibits EBV DNA replication may be effective in some patients during the polyclonal growth phase but is ineffective once the tumor evolves into a monoclonal lymphoma. We have identified several factors that may be useful in predicting responsiveness to acyclovir therapy.

Acyclovir↗
PubMed1984

Cellular basis of allograft rejection.

In summary, we currently hypothesize that systemic immunization within the lymphoid tissue is amplified by a sequence of specific and non-specific immunological interactions which lead to enrichment of specifically sensitized T-cells at the graft site. Nascent sensitized cells enter the graft via non-specific attractants generated by the healing response. The interaction of alloantigen with responder T-cells bearing specific alloantigen receptor results in production of lymphokines which increase blood flow and vascular permeability, and which are chemotactic for circulating lymphocytes. These events and other non-specific events recruit circulating cells regardless of the specificity of their sensitization. The state of activation of these cells may control their presence within the circulation. Cells which are more activated are released more readily from the lymphoid depots into the circulation so that relatively more specifically sensitized (though not necessarily mature cytotoxic cells) cells would enter the circulation and be recruited to the graft. At the allograft, there is an escalating sequence of lymphokine production and non-specific recruitment. II-1 has been demonstrated to be capable of mediating such recruitment. A second phase of amplication occurs at the graft site where precytotoxic (x-ray-sensitive) cells mature and expand into cytotoxic (x-ray-resistant) cells. These cells may be important effector cells of allograft rejection in concert with many unsensitized cells which can participate in non-specific attacks on graft viability. The essential point made from the studies summarized here is the consideration that trafficking patterns of lymphocytes and recruitment of lymphocytes and other inflammatory cells are in essential component to the local mechanism of graft rejection. The relative importance of specificity of response has not been defined.

Animals↗