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Biomedical subjects

D B Brubaker

Publications and source records attributed to D B Brubaker.

At least 19 recordsLinked to original sources
PubMed2000

In vitro bleeding time test can diagnose thrombotic thrombocytopenia purpura and can possibly monitor therapeutic plasma apheresis.

Thrombotic thrombocytopenia purpura (TTP) is perplexing, mainly because of its difficult diagnosis and dramatic clinical presentations, high mortality rates, and the effectiveness of empirical plasma infusions and plasma exchanges. Scientific evidence supports the hypothesis that TTP results from platelet hyperagglutination. To support this, a new in vitro bleeding time (Platelet-Stattrade mark) test was used. Eleven patients had a mean in vitro bleeding time of 7.3 +/- 2.1 seconds prior to plasma exchange and eight patients had a mean of 13.6 +/- 4.7 seconds after the plasma exchange procedure. Normal controls were 14 +/- 2 seconds. The test was used to monitor plasma exchanges in two patients. At the time the platelet count and LDH returned to normal, the Platelet-Stattrade mark remained shortened. The two patients relapsed and required continued plasma exchanges until Platelet-Stattrade mark corrected to normal. These results suggest that plasma exchanges may be effectively monitored by Platelet-Stattrade mark rather than the traditional parameters, i.e., LDH. Therefore, the Platelet-Stattrade mark test may be a useful test to diagnose TTP and monitor therapy in this disease.

Bleeding Time↗
PubMed1998

Intravascular and total body platelet equilibrium in healthy volunteers and in thrombocytopenic patients transfused with single donor platelets.

Instrument platelet counts used in corrected count increment (CCI) and percent platelet recovery (PPR) formulas presume the transfused platelets are in equilibrium during the first hour after platelet transfusion. The timing of the pre-transfusion count affects CCI results, and we postulate that timing of CCI post transfusion affects CCI results. Platelet equilibrium using indium-111 platelet transfusions has not been reported. Platelet redistribution was studied in 16 healthy volunteers and 12 thrombocytopenic patients by generally infusing less than 72-hr stored single-donor platelets along with an aliquot of indium-111-labeled platelets by intravenous push. Counts were measured at 10, 15, 20, 60, and 120 min, and 24, 48, 72 hr along with continuous body scanning for 2 hr in healthy volunteers, and static organ scanning in patients and volunteers. Results indicated transfused platelets do not reach intravascular equilibrium for 60 min post-infusion and that the 10-min count cannot detect platelet refractoriness. However, total body equilibrium varies considerably between normal volunteers and thrombocytopenic patients. It is recommended to continue with the 1-hr post transfusion count.

Antigens, Human Platelet↗
PubMed1993

Immunopathogenic mechanisms of posttransfusion graft-vs-host disease.

Posttransfusion graft-versus-host disease is a lethal adverse effect of blood transfusions affecting the skin, liver, gastrointestinal tract, and, in addition, the lymphohematopoietic systems. It is a disease that has been described for nearly three decades with well over 400 cases known worldwide; however, the immunopathogenesis has not been fully described. By using murine models, combined with human case reports, the immune mechanism and risk factors are outlined. The models and case reports prove a histocompatibility disparity between donor and recipient. The dose of lymphocytes in the products, types of T lymphocyte subsets in the products, and degree of immune suppression in the host are all factors necessary in the immunopathogenesis of posttransfusion graft-versus-host disease. The mechanism is that of acute, lethal, suppressive immune dysregulation in the host (recipient).

Animals↗
PubMed1992

The function of elevated plasma fibronectin in preeclampsia.

Total plasma fibronectin is elevated in preeclampsia due to vascular injury release, increased production, or enzymatic degradation resulting in multimers. To examine the etiology of the fibronectin increase in preeclampsia, we quantified plasma fibronectin in nonpregnant women, pregnant women from 28 to 42 weeks' gestation, latent labor, and preeclampsia by both nephelometry and turbidimetry. Western blotting and gel electrophoresis were used to examine the structural integrity of the fibronectin molecule. In addition, functional assays explored the potential for dysfunctional fibronectin. Fibronectin was elevated in pregnant patients compared with nonpregnant patients and exhibited a further significant increase with preeclampsia. The increase was not a result of degradation to multimers but possibly to increased variants. Notably, fibronectin function, as defined by collagen binding, may be impaired during pregnancy and preeclampsia. It appears that the clinical pathophysiology of preeclampsia may be related to dysfunctional fibronectin measured by collagen binding.

Blotting, Western↗
PubMed1990

Clinical significance of white cell antibodies in febrile nonhemolytic transfusion reactions.

Febrile nonhemolytic transfusion reactions (FNHTRs) are associated with white cell (WBC) antibodies. The purposes of this study were to determine the frequency of WBC antibodies, to associate the severity of reactions with antibody specificity, and to distinguish FNHTRs from infection and postoperative fever. By using the granulocyte indirect immunofluorescence test in conjunction with lymphocytotoxicity testing, it was found that 70 percent of FNHTRs in 24 patients involved WBC antibodies. The remaining 30 percent of apparent FNHTRs were associated with infections and postoperative fever. Granulocyte-specific antibodies were as prevalent as HLA antibodies and were associated with the severest reactions. Because FNHTRs occur with granulocyte-specific antibodies, HLA antibodies, and possible monocyte-specific antibodies (untested in this and other studies), these reactions could be grouped together as WBC-associated reactions.

Adult↗
PubMed1989

An in vitro bleeding time test.

A new conical plastic device and method, the Platelet-Stat test, has been developed to measure in vitro bleeding time. Ten milliliters of citrated blood, collected by venipuncture, was used. The in vitro bleeding time test was validated by several criteria. Eight volunteers tested had a mean bleeding time of less than 1 minute. Different anticoagulants were evaluated, and the test performed optimally with citrate. Within-run precision had a mean time of 39 +/- 6.7 seconds with a coefficient of variation of 17%. An aspirin study was done on eight volunteers. Preaspirin in vitro bleeding time was less than 1 minute, whereas postaspirin times were more than 7 minutes at 18-24 hours. This test is a reproducible method of performing the bleeding time with greater precision than the in vivo test.

Anticoagulants↗
PubMed1989

Use of platelets in transfusion medicine.

Platelet transfusions are beneficial to treat or prevent bleeding in the thrombocytopenic patient. They are frequently used in patients with hypoplastic bone marrow, in cardiovascular surgery patients, and those involved in trauma. Because platelets have short survival, large numbers of platelet units are required. Also, platelet transfusions are expensive and not without complications. They can cause alloimmunization, provoke transfusion reactions, or transmit infectious disease, of which hepatitis C (non-A, non-B hepatitis) is of greatest concern. Therefore, documented indications and close monitoring of the transfused platelets are necessary.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Predictive value of enzyme-linked immunoassay platelet crossmatching for transfusion of platelet concentrates to alloimmunized recipients.

Some evidence has shown that platelet crossmatching is useful in multitransfused patients with hypoplastic bone marrows who are refractory to platelet therapy through alloimmunization. Several immunoglobulin binding assays other than enzyme-linked immunospecific assay (ELISA) have been studied previously. We performed 51 ELISA crossmatches on six patients receiving single donor platelets. One bone marrow transplant patient receiving 33 single donor HLA matched (related and unrelated) was also studied. Effectiveness of transfusion was closely monitored by patient evaluation and corrected platelet count increment (CCI) at 1-2 and 18-24 hours posttransfusion. We found the ELISA method very sensitive, specific, and predictive, 85, 96, and 95.6% respectively in the 51 crossmatches studied in six patients with either leukemia, solid tumors, or aplastic anemia. However, variation existed among individual recipients, with sensitivity ranging from 70-100%. The distribution of true positives and negatives and false positives and negatives in the 33 crossmatches performed in the bone marrow transplant patient differed significantly (chi 2 = 101.2; P less than 0.001) from single donor recipients. The specificity in the 51 crossmatches on the six patients was also significantly different from the 33 crossmatches performed in the bone marrow transplant (96 vs 74%). This suggests individual variation occurs as well as differences in diseases and bone marrow suppressive agents affecting platelet crossmatching.

Blood Grouping and Crossmatching↗
PubMed1987

Relationship of HLA and platelet-reactive antibodies in alloimmunized patients refractory to platelet therapy.

Platelet crossmatching assays have been used to predict the outcome of platelet transfusions in alloimmunized patients by detecting antibodies against platelets. The transfusion failure of HLA-matched platelets predicted by platelet crossmatching may be related to HLA antibodies undetected by lymphocytotoxicity but detected by platelet immunoglobulin-binding assays or platelet-specific antibodies (both antibodies defined here as platelet-reactive antibodies). To differentiate platelet-reactive antibodies from lymphocytotoxic HLA antibodies, we used HLA characterized lymphocytes in parallel with platelets from individuals to form separate frozen panels. Sera from 10 allosensitized patients were studied in the lymphocyte panel by lymphocytotoxicity and in the platelet panel by enzyme-linked immunoassay (ELISA). By comparing pattern and percent wells reacting in each panel, lymphocytotoxic HLA antibodies and antibodies reactive with platelets in ELISA were detected separately. In all 10 allosensitized patients, platelet-associated antibodies were present and 7 had additional lymphocytotoxic HLA antibodies. Using this double parallel panel technique, we found platelet-reactive antibodies important in platelet alloimmunization, unrecognized by lymphocytotoxicity. These data indicate platelet-crossmatching be solely used in the selection of platelets for allosensitized patients.

Blood Platelets↗
PubMed1987

Four immunoassay methods and standards compared for measuring fibronectin.

Several companies have developed commercial kits to measure plasma fibronectin rapidly and inexpensively with readily available laboratory equipment. In two of these kits (Cooper Biomedical and Boehringer-Mannheim) an immunoturbidimetric method is used. In a third kit (Biomedical Technologies, Inc.) an enzyme immunoassay method is used. To evaluate these commercial kits for fibronectin assay, we selected nephelometry as a comparison method for ranking the kits with regard to precision and accuracy. We also compared antibody and fibronectin cross reactivity. The antibodies from various manufacturers appear similar, but the fibronectin standards from different sources showed significant variation. Rate nephelometry and the Boehringer-Mannheim kit had the best within-run precision (CVs of 0.38% and 5.5% respectively). Between-run precision for nephelometry was excellent (CV = 1.9%) and somewhat high for the Boehringer-Mannheim kit (CV = 15.4%). This study demonstrates a need for further standardization of antigen (fibronectin) and antibody in commercial kits and the development of suitable stable quality-control material.

Antibodies↗
PubMed1983

Demonstration of cells bearing the OKT6 determinant in human tonsil and lymph node.

An immunoperoxidase study was carried out on human tonsil (15 specimens) and human lymph node (5 specimens) using OKT6, a monoclonal antibody which was raised against a determinant on immature thymocytes. OKT6-positive cells were identified in the crypt epithelium of all tonsils examined and in occasional clusters in the interfollicular areas of two lymph nodes. OKT6 has recently been shown to react with epidermal dendritic cells (Langerhans' cells). This study confirms that OKT6-reactive cells may be found outside the thymus. The pattern of staining obtained suggests that OKT6 reactivity belongs to a dendritic subpopulation. The significance of the finding in relation to physiology and pathology is discussed. These physiological findings may also be relevant to the immunotherapy of T-cell lymphomas.

Antibodies, Monoclonal↗
PubMed1983

Detection of platelet antibodies using the platelet migration inhibition assay.

We evaluated the usefulness of the Platelet Migration Inhibition (PMI) assay in detecting antibody to platelets in patients receiving platelet transfusions. Forty-one PMI assays were performed on pretransfusion sera from 19 patients. After each transfusion, each patient was evaluated clinically and by transfusion response for alloimmunization. Prevalence of antiplatelet antibody, the predictive value of positive and negative results, and efficiency of the PMI assay were calculated. The 41 PMI assays yielded true-positive, true-negative, false-positive, and false-negative results of 18, 14, 5, and 4, respectively. The sensitivity and specificity of the PMI assay were calculated at 81.8% and 73.7%. The PMI assay was comparable in sensitivity and specificity to immunofluorescence and superior to platelet aggregation and lymphocytotoxicity for detecting platelet (inhibition) antibodies. This test is simple and less costly than immunofluorescence; however, it lacks speed and efficiency for crossmatching purposes. It is useful as a clinical test in screening potential platelet pheresis donors and patients receiving platelet transfusions every other day. It may prove useful in research as a functional test to understand alloimmunization and restricted alloimmunization.

Blood Platelets↗
PubMed1983

Human posttransfusion graft-versus-host disease.

Graft-versus-host disease (GVDH) follows blood product transfusions in patients with deficient cell-mediated immunity. The rate of mortality in this adverse effect of blood transfusions is between 90 and 100%. The historical; clinical and pathologic; and mechanism of acute and chronic GVHD are presented. The patients at risk, the clinical and pathologic features of posttransfusion GVDH have been presented in hopes that, with increased awareness of this usually fatal complication, clinicians and transfusion therapists may more intelligently advise and select patients who may need lymphocyte-poor or irradiated blood products and may recognize the syndrome earlier.

Acute Disease↗