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R Storb

Publications and source records attributed to R Storb.

At least 649 records · Page 36Linked to original sources
PubMed1982

Acute and chronic graft-versus-host disease in dogs given hemopoietic grafts from DLA-nonidentical littermates. Two distinct syndromes.

We recognized two distinct clinical and histologic syndromes of acute and chronic graft-versus-host disease (GVHD) in irradiation chimeric dogs given hemopoietic grafts from DLA-nonidentical littermate donors. Clinically acute GVHD developed, with a median onset of 13 days after the transplant, and was characterized by skin erythema, jaundice, diarrhea, and gram-negative infections; the median survival of these dogs was 29.5 days. Chronic GVHD developed a median of 124 days after the transplant and was characterized by generalized skin ulcerations, massive ascites, and gram-positive infections; the median survival of these dogs was 150 days. Chronic GVHD could be distinguished histologically from acute GVHD by epidermal atrophy and dermal fibrosis and by bile duct proliferation, bridging, piecemeal necrosis, and portal fibrosis in the liver. Questions related to GVHD in man can be investigated in this model of acute and chronic GVHD in a large outbred species.

Acute Disease↗
PubMed1982

Interruption of tumor-associated platelet consumption with platelet enzyme inhibitors.

Twenty dogs with naturally occurring metastatic tumors were treated with anticoagulants (Warfarin) or platelet enzyme inhibitor drugs (dipyridamole, dipyridamole plus aspirin, RA233, sulfinpyrazone, or a combination of RA233 and sulfinpyrazone) to determine if tumor-related reductions in platelet survival and concentration could be reversed. Anticoagulation was ineffective, while platelet enzyme inhibitors were able to produce improvements in platelet survival. Of the 18 dogs with metastatic tumor treated with platelet enzyme inhibitors, only 5 (28%) showed a reduction in platelet survival during the first week of observation on therapy compared to their baseline survivals. This is significantly different than the decreases in platelet survivals observed in 8 of 10 untreated dogs (80%) with metastatic tumor observed for the same interval. Furthermore, 8 of the 18 treated dogs (44%) had platelet survivals within 2 standard deviations of normal, compared to only 1 of 10 untreated dogs. Of the 8 dogs with normal platelet survivals, 6 were treated with a combination of a phosphodiesterase inhibitor (RA233 or dipyridamole) and a cyclooxygenase inhibitor (sulfinpyrazone or aspirin). The combination of RA233 and sulfinpyrazone was the best drug program tested and resulted in normal platelet survivals in 63% and improved platelet counts in 75% of the animals treated. Thus, platelet enzyme inhibitors with different mechanisms of action may have a synergistic effect in reversing the abnormal platelet hemostasis found in a variety of spontaneously occurring canine neoplasms.

Animals↗
PubMed1982

Two monoclonal antibodies (DLy-1 and DLy-6) directed against canine lymphocytes.

Two murine monoclonal antibodies directed against canine lymphocytes are described. DLy-1, raised against puppy thymocytes, and DLy-6, raised against bronchoalveolar lymphocytes, both react with most lymphocytes in peripheral blood, thoracic duct lymph, and bronchoalveolar lavage fluids. DLy-1 also recognizes monocytes and granulocytes. However, it is not reactive with erythrocytes, megakaryocytes, or platelets. Expression of DLy-1 antigen on thymocytes ranged from 5--30%. The distribution of DLy-6 antigens seems to be confined to lymphoid cells. Ten to 60% puppy thymocytes were positive. Interestingly, lymphoblasts formed in response to stimulation with mitogens or alloantigens lacked DLy-6 in contrast to DLy-1 cell surface antigen expression.

Animals↗
PubMed1982

Marrow transplantation with or without donor buffy coat cells for 65 transfused aplastic anemia patients.

Sixty-five multiply transfused patients with severe aplastic anemia were given cyclophosphamide followed by grafts anemia were given cyclophosphamide followed by grafts from HLA-identical siblings. The effect of the administration of viable donor buffy coat cells following the marrow inoculum was evaluated with regard to graft rejection and survival. Results in 43 patients so treated are presented along with those in 22 concurrent patients given marrow alone. Most patients given buffy coat had positive in vitro tests of sensitization indicating a high risk for graft rejection, while all but one of the patients given marrow alone had negative tests. Thirty of the 43 (70%) patients given marrow and buffy coat are alive between 10 and 61 mo (median 36) after grafting; 4 died after graft rejection and 6 with acute or chronic graft-versus-host disease (GVHD). Eleven of the 22 (50%) patients given marrow alone are alive between 29 and 65 mo (median 52); 7 died after graft rejection and 3 with GVHD. The addition of buffy coat cell infusions to the marrow inoculum reduced the risk of rejection and increased survival in the currently reported transfused patients when compared to patients grafted before 1976. However, there was an increased risk of chronic GVHD. Recipients of marrow from female donors survived slightly better (73%) than recipients of male marrow (58%).

Adolescent↗
PubMed1982

Low serum thymic hormone levels in patients with chronic graft-versus-host disease.

We tested the hypothesis that chronic graft-versus-host disease (GVHD) is due to inadequate thymic function by examining pretransplant serum levels of facteur thymique serique (FTS). Four of five patients with no detectable FTS activity developed chronic GVHD, while one of four with some FTS activity did. Further patient numbers are needed to confirm or reject this hypothesis. We further postulated that chronic GVHD, whatever its cause, involves thymic epithelium as a target organ. When tested 11 mo or more posttransplant, patients with chronic GVHD had lower absolute FTS levels (p less than 0.02) and lower age-corrected levels (p = 0.05) than patients without chronic GHVD. Low values in chronic GVHD were associated with the disease itself and not its therapy. These findings show that thymic epithelial secretory function is impaired in chronic GVHD, and this may in part be responsible for the immunodeficiency characteristic of these patients.

Adolescent↗
PubMed1982

Cyclosporin-A abrogates transfusion-induced sensitization and prevents marrow graft rejection in DLA-identical canine littermates.

Previous studies had shown that marrow graft rejection generally did not occur in untransfused dogs given 900-rad total body irradiation and hemopoietic grafts from DLA identical littermates (only 1 of 59 rejected), but was seen in all instances after three preceding transfusions of whole blood from the marrow donor on days -24, -17, and -10 before transplantation (19 of 19 rejected). The present study was undertaken to investigate whether immunization by 3 preceding transfusions of whole blood from the DLA-identical littermate marrow donor could be abrogated by administration of the immunosuppressive agent cyclo-sporin-A, 20 mg/kg/day intramuscularly on days -5 to 0. Seven of 10 dogs showed sustained marrow engraftment. 2 failed to engraft, and 1 dog died to early to be evaluated. It was concluded that immunization to non-DLA antigens by preceding whole blood transfusions could be abrogated in most cases by a short-course of cyclosporin-A before total body irradiation and marrow transplantation, resulting in successful and sustained marrow engraftment.

Animals↗
PubMed1981

A comparison of marrow transplantation with chemotherapy for children with acute lymphoblastic leukemia in second or subsequent remission.

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.

Adolescent↗
PubMed1981

Treatment of graft-versus-host disease in human allogeneic marrow graft recipients: a randomized trial comparing antithymocyte globulin and corticosteroids.

This prospective randomized trial compared the effect of antihuman thymocyte globulin (ATG) versus corticosteroids as treatment of graft-versus-host disease (GVHD) in recipients of HLA-identical allogeneic bone marrow transplants. Patients undergoing transplantation as therapy for either hematologic malignancies or aplastic anemia were given methotrexate as postgrafting immunosuppression. Patients who nevertheless developed acute GVHD of moderate severity were randomized to receive either corticosteroid therapy or ATG therapy. Thirty-seven patients were randomized: 20 patients received corticosteroids, and 17 received ATG. Both ATG and corticosteroids were in general well tolerated, although all patients receiving ATG developed fever and chills. Both treatment modalities were associated with a mild decrease in severity of GVHD after therapy. There was, however, no significant difference between treatment groups, whether assessed by improvement in specific organ involvement, improvement in the overall grade of GVHD, need for additional therapy for acute GVHD, or the proportion of patients who developed chronic GVHD. Infectious complications and survival were also not different between treatment groups. Thus, corticosteroids were as effective as ATG for the treatment of acute GVHD in recipients of HLA-identical marrow transplants and, therefore, appear to be a reasonable choice as primary therapy for acute GVHD.

Adult↗
PubMed1981

The use of hemolysis-in-gel assays to study polyclonal antibody secretion in bone marrow transplant recipients.

Polyclonal antibody secretion was measured as direct plaque-forming cells (PFC) against fluorescein isothiocyanate coupled sheep red blood cells (FITC-SRBC) or in an indirect assay using protein A coupled SRBC and anti-sera against human IgG, IgA, and IgM. Eighty individuals who were recipients of bone marrow transplants and 66 healthy controls were studied. Lymphocytes from patients studied during the first three months (short-term patients) had deficient B-cell function in both assays compared to normals. In healthy controls the direct assay only detected about 4% of the IgM producing B cells found in the indirect assay. PFC in long-term patients were not different from that of controls except for patients with chronic graft-versus-host disease (GVHD) who had a deficient IgM production. Patients with acute GVHD had unusual high numbers of IgG PFC after Staph. aureus activation (p less than 0.001). Short-term patients with infections had increased (p less than 0.01) IgG and IgA after Staph. aureus activation. PFC assays performed in three patients with grafts from HLA-nonidentical donors showed an increase in the background cultures for IgG PFC (p less than 0.025) and an increased IgG PFC after Staph. aureus stimulation (p less than 0.01) compared to patients with HLA-identical donors.

Adolescent↗