Biomedical subjects

D F Stroncek

Publications and source records attributed to D F Stroncek.

81 records · Page 5Linked to original sources

PubMed1984

Effect of dialyzer reuse on complement activation and neutropenia in hemodialysis.

A prospective study of 10 patients undergoing hemodialysis showed that less neutropenia and complement activation occurred with dialyzer reuse. Neutrophil counts fell 95% +/- 5% (SEM) with first use and 66% +/- 8% and 48% +/- 10% with second and third uses, respectively (p less than 0.05). The production of complement component C5a-desarg, as measured by the bioassay granulocyte aggregation, was decreased by 96% +/- 1% and 93% +/- 2% with second and third uses, respectively (p less than 0.05). We investigated the role of the dialyzer disinfectant formaldehyde in decreased neutropenia. In vitro, formaldehyde inhibited granulocyte aggregation and chemotaxis and the dialyzer membrane's ability to generate granulocyte aggregating activity; however, this occurred only at concentrations higher than those likely to obtain in patients. The ability of dialysis membranes to generate granulocyte aggregating activity in plasma was decreased 55% +/- 5% by their prior sequential preincubation in plasma and then formalin (p less than 0.05) and extensive rinsing, which is similar to the circumstances obtaining with dialyzer reuse. Preincubation of membranes in plasma or formalin alone resulted in no change in the membrane's ability to generate granulocyte aggregating activity. We conclude that the exposure of membranes to both plasma and formalin during dialysis and storage is responsible for the decreased C5a-desarg production with reuse, probably because plasma proteins are fixed to the membrane in such a way that interrupts free interaction between the membrane and plasma complement components.

Agranulocytosis↗

PubMed1981

Complement activation and neutropenia occurring during cardiopulmonary bypass.

Complement activation and pulmonary leukostasis with neutropenia occur in hemodialysis and filtration leukapheresis, with attendant pulmonary dysfunction. Wondering whether similar phenomena might attend cardiopulmonary bypass (CPB), we studied 34 patients undergoing coronary artery bypass operations. As in the other extracorporeal circulation systems, neutropenia (mean 44.7% +/- 4.3% SEM of prebypass PMN count) occurred during the first half hour of bypass and then a rebound neutrophilia followed. CH50 and C3H50 fell 22% to 25% (p for CH50 less than 0.01) during bypass, but C3 conversion and C5a were not demonstrable in patient plasmas. Nonetheless, polymorphonuclear neutrophils (PMNs) harvested late in bypass showed low adherence to nylon and selective chemotactic and aggregative insensitivity to C5a--functional aberrations which are seen after exposure to activated complement. Furthermore, smaller infusions of activated complement into animals produced neutropenia than were required to achieve a detectable [C5a] in the plasma. We conclude that neutropenia during CPB probably results from complement activation below the threshold of detection; complement-stimulated PMNs deserve study as possible mediators of tissue injury occurring during CPB.

Agranulocytosis↗

PubMedDate not supplied

HLA class I and II antigen phenotypes of North American Indians from Minnesota: implications for marrow transplants using unrelated donors.

As a result of an appeal for a bone marrow donor for a North American Indian (Native American) patient, 261 Native Americans from our community were typed for HLA-A,B,DR antigens, and 51 were typed for HLA-A,B antigens only. The HLA antigen frequencies of the Native Americans were compared with those of 12,881 white bone marrow donors and were found to differ markedly. To investigate the implications these differences in HLA antigen frequencies would have for the location of unrelated bone marrow donors, the HLA types of 12 Native American bone marrow transplant patients from our institution were used to search among 5389 HLA-A,B,DR-typed white donors in the National Marrow Donor Program file and the file of 261 HLA-A,B,DR-typed Native American donors. In the white donor file, at least two donors were found that matched at all HLA-A,B,DR antigen loci of one Native American patient (8%). Using the Native American donor file, which was less than one-twentieth the size of the white donor file, and HLA-A,B,DR-matched donor was also found for one (8%) of the patients. These results suggest that although donors for nonwhites can be identified in a file of HLA-typed white volunteers, the probability of finding a suitably matched donor for such individuals is enhanced if donors representing racial or ethnic minorities are included in unrelated donor registries.

Bone Marrow Transplantation↗

PubMedDate not supplied

Adverse reactions in patients transfused with cryopreserved marrow.

Marrow is cryopreserved for use in autologous bone marrow transplants, but little is known of the incidence of reactions in patients transfused with these cryopreserved marrows. Reactions in patients transfused during a 4-year period with 134 autologous marrows cryopreserved in dimethyl sulfoxide (DMSO) were compared with those in patients transfused with marrow that had been collected from HLA-compatible donors and that had not been cryopreserved. Patients transfused with cryopreserved marrow had significantly more nausea (44.8 vs. 14.1%; p less than 0.0005), vomiting (23.9 vs. 8.5%; p less than 0.01), chills (31.3 vs. 1.4%; p less than 0.0005), and fever (17.9 vs. 0%; p less than 0.005) than patients transfused with fresh allogeneic marrow. The incidence of emesis correlated with the dose of DMSO received, but that of nausea did not. All cryopreserved marrows were cultured for bacteria at the time of transfusion and 17 (12.7%) were found to be positive. Only 1 of the 17 patients transfused with culture-positive marrow developed sepsis during the transplant course with the same organism that was present in the transfused marrow. Although the reactions in donors transfused with cryopreserved marrow were readily treated, this study suggests that the incidence of some reactions might be decreased by reducing the dose of DMSO transfused. Bacterial contamination of transfused marrow was a worrisome complication, and efforts should be made to improve marrow collection and processing techniques to minimize that risk.

Bacteria↗

PubMedDate not supplied

Effects on donors of second bone marrow collections.

Second bone marrow transplants have been used successfully to treat marrow graft failure or relapse following the original marrow transplantation. Hospital records of 16 related two-time bone marrow donors were reviewed to determine what risks a person faces in making a second marrow donation. One donor suffered a minor complication following the first collection, but no donors suffered complications during the second donation. The volume of marrow collected for the first and second donations (1253 +/- 504 vs. 1261 +/- 471 mL) was similar. However, more marrow donors received transfusions of homologous red cells during the second collection than during the first collection (5/16 compared to 1/16; p = 0.06). To determine what factors might contribute to the high incidence of homologous red cell transfusion during second donations, the experiences of donors who received homologous blood during the second donation were compared to the experiences of donors who received only autologous blood. Persons receiving homologous blood during the second collection received more red cell units than persons receiving autologous blood (2.0 +/- 0.7 units compared to 0.9 +/- 0.5 units; p less than 0.01). Their precollection hemoglobin levels were lower (12.3 +/- 1.2 vs. 14.4 +/- 1.4 g/dL [123 +/- 12 vs. 144 +/- 14 g/L]; p less than 0.01), and the time between the first and second collections was significantly less (45 +/- 8 days vs. 342 +/- 432 days; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMedDate not supplied

Characterization of the neutrophil molecules identified by quinine-dependent antibodies from two patients.

BACKGROUND: Two patients with episodic pancytopenia and renal failure associated with quinine (Qn) ingestion were previously found to have Qn-dependent antibodies that reacted with red cells, platelets, and neutrophils. The purpose of these studies was to characterize the neutrophil antigens recognized by Qn-dependent antibodies from these two patients. STUDY DESIGN AND METHODS: The neutrophil molecules recognized by the Qn-dependent antibodies in the sera from the two patients were analyzed by immunoprecipitation using 125I-labeled neutrophils. Neutrophils from 13 different donors were tested. RESULTS: The Qn-dependent antibodies from Patient 1 immunoprecipitated a 60-kDa molecule on neutrophils from seven donors and an 85-kDa molecule on neutrophils from three donors. The Qn-dependent antibodies from Patient 2 reacted with a 32-kDa molecule on neutrophils from 5 donors, a 60-kDa molecule on neutrophils from 9 donors, and an 85-kDa molecule on neutrophils from 10 donors. Neutrophil-specific antigen NB1 is also located on a 60-kDa glycoprotein (GP). While the antibody in serum from Patient 1 did not show specificity for NB1, the antibody from Patient 2 detected the 60-kDa molecule on NB1-positive neutrophils from 9 of 11 donors tested and did not detect the 60-kDa molecule on NB1-negative neutrophils from 2 donors. In a monoclonal antibody immobilization of granulocyte antigens assay, the Qn-dependent antibody from both patients reacted with the 60-kDa molecule carrying NB1. The Qn-dependent antibody from a third patient, Patient 3, was previously found to react with an 85-kDa GP and the 60-kDa NB1 GP. To determine if the Qn-dependent antibodies from Patients 2 and 3 recognized the same 85-kDa GP, neutrophils were treated with serum from Patient 3 plus Qn to remove the 85-kDa GP. Then, serum from Patient 2 plus Qn no longer immunoprecipitated the 85-kDa GP. CONCLUSION: The antigens recognized by Qn-dependent neutrophil antibodies were located on molecules of 85, 60, and 32 kDa. Qn-dependent antibodies from two patients reacted with the same 85-kDa GP and those from three patients reacted with the same 60-kDa GP. The 60-kDa molecule recognized by the Qn-dependent antibodies carried the NB1 antigen.

Antibodies↗

PubMedDate not supplied

Mislabeling of elutriation medium: a demonstration of the need to improve the quality control of reagents produced for cell processing.

BACKGROUND: The processing of hematopoietic cells to remove red cells, T-lymphocytes, or malignant cells has become common. However, few of the reagents used are produced specifically for marrow processing and approved by the Food and Drug Administration. CASE REPORTS: A labeling error is reported in a commercially manufactured, research-grade reagent used in an elutriation procedure to deplete T cells from mononuclear cells obtained from bone marrow for allogeneic transplantation. The elutriation medium used in the procedure had been labeled as containing 0.9-percent sodium chloride, 0.1-percent dextrose, and 0.3 mM EDTA, but it actually contained 3.0 mM EDTA. When this medium was not available from the manufacturer, it was prepared in this hospital, according to the stated formulation, with 0.3 mM EDTA. When marrows from two unrelated donors were processed with this 0.3 mM EDTA-containing medium, cell loss due to aggregation occurred, and, in one recipient, the marrow did not engraft. After the error in the medium composition was discovered, marrow was collected a second time from the same donor. The marrow was processed with medium containing 3.0 mM EDTA, and no cell aggregation was observed. CONCLUSION: Food and Drug Administration-approved reagents, prepared specifically for use in cell processing and produced according to good manufacturing practices, should be used whenever possible.

Bone Marrow Cells↗

PubMedDate not supplied

Alloimmunization after granulocyte transfusions.

BACKGROUND: Although granulocyte transfusions are recommended for neutropenic patients with bacterial infections that are unresponsive to antibiotic therapy, the presence of white cell (WBC) antibodies in the recipient can render these transfusions ineffective. STUDY DESIGN AND METHODS: A 25-year-old man with chronic granulomatous disease experienced a pulmonary transfusion reaction while receiving granulocyte transfusions, and he was found to be immunized to neutrophil antigen NA2. A retrospective study of alloimmunization to HLA and neutrophil antigens in 18 patients with chronic granulomatous disease who had also received repeated granulocyte transfusions was then performed. Sera were tested in lymphocytotoxicity, granulocyte agglutination, granulocyte immunofluorescence, monoclonal antibody immonobilization of granulocyte antigen, and immunoprecipitation assays. RESULTS: After the granulocyte transfusions, sera from 14 of the 18 patients contained WBC antibodies. Seven sera samples reacted in the lymphocytotoxicity, granulocyte immunofluorescence, and granulocyte agglutination assays; seven reacted in the lymphocytotoxicity and granulocyte immunofluorescence assays but not the granulocyte agglutination assay, and four did not react. When the monoclonal antibody immobilization of granulocyte antigen assay was used, three sera samples reacted with Fc gamma receptor III, three with the 58- to 64-kDa protein carrying the neutrophil antigen NB1, one with CD11a, and one with CD18. Antibodies from three patients immunoprecipitated a neutrophil protein of 60 kDa. Overall, antibodies to neutrophil antigens other than HLA could be detected in sera from eight patients. Transfusion reactions occurred in 11 of the 14 individuals with WBC antibodies and in none of the 4 without antibodies. Seven pulmonary reactions occurred in patients with WBC antibodies. The patients with WBC antibodies were given significantly more granulocyte concentrates (78 +/- 65 vs. 29 +/- 15 units, p < 0.05). CONCLUSION: Recipients of granulocyte transfusions often become alloimmunized. Screening for WBC antibodies periodically during transfusions, after adverse reactions, or before subsequent transfusions is indicated. If WBC antibodies are present, no further granulocyte transfusions should be given unless the granulocytes are collected from HLA- and/or neutrophil antigen-compatible donors.

Adolescent↗

PubMedDate not supplied

Neutrophil oxidants inactivate alpha-1-protease inhibitor and promote PMN-mediated detachment of cultured endothelium. Protection by free methionine.

Activated granulocytes have been implicated in mediating pulmonary endothelial damage in the Adult Respiratory Distress Syndrome. In another lung disease, emphysema, pulmonary granulocytes (PMNs) are thought to be doubly responsible for lung dissolution: they release potent proteolytic enzymes including elastase, and they generate reactive oxygen species that oxidize a reactive site methionine group in alpha-1-protease inhibitor (alpha-1-PI) rendering it, in turn, impotent as an anti-elastase. This suggested an analogous scenario for pulmonary vascular damage: namely, undefended PMN elastase might also mediate endothelial injury. Our strategy to prove this notion used 51chromium-labeled human endothelial cells exposed to intact PMN or to enucleate "neutroplasts." The latter are elastase-free cytoplasmic blebs derived from PMN. When activated, both PMN and neutroplasts generate similar amounts of toxic oxygen species; yet neutroplasts caused insignificant endothelial damage, measured as 51Cr "lift-off"from anchoring matrix (PMN = 24.3% +/- 1.8% vs neutroplast = 1.2% +/- 0.4%; p less than 0.001). Adding pure elastase back to neutroplasts increased endothelial cell lift-off (7% +/- 0.2%). Although the prototypic serine protease inhibitor phenyl methylsulfonylfluoride (PMSF) protected endothelium from PMNs, pure alpha-1-PI (also a potent anti-elastase) when added in physiologic amounts did not protect endothelial cells from PMN assault, suggesting that PMN oxidants might inactivate it. By adding exogenous myeloperoxidase (MPO) to MPO-deficient neutroplasts, we demonstrated that MPO-dependent oxidants, probably N-chloramines, are critical inactivators of alpha-1-PI. This was further confirmed since added free methionine, a scavenger of chloramine, protected alpha-1-PI from inactivation by reagent chloramine or that produced by rearmed neutroplasts or PMN.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Proteins↗