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Biomedical subjects

K McGrath

Publications and source records attributed to K McGrath.

At least 55 records · Page 3Linked to original sources

Transient platelet and HLA antibody formation in multitransfused patients with malignancy.

Fifty-nine patients receiving platelet transfusions for bone marrow failure secondary to malignancy were screened at regular intervals for the presence of antibodies to human leucocyte (HLA) and platelet specific antigens. HLA antibodies occurred in 19 patients, 10 of whom also developed platelet specific antibodies. The HLA antibodies disappeared in 10 of 15 patients followed for periods of 2-14 months. In two patients this occurred whilst still receiving platelet transfusions. Antibody reappeared in only two of six patients subsequently transfused. Antibodies to platelet specific antigens were detected in 28 patients. They were transient, often appeared in association with infection, and in 50% of cases tested demonstrated autoantibody activity. There was no association with antibiotic drug therapy, or PFA/EDTA-dependent cryptantigens. Platelet recovery at 1 h or 20 h post transfusion was not significantly reduced in the presence of platelet specific antibodies. These findings have important implications for the selection of platelet donors for alloimmunized recipients.

Antibodies↗

A new regimen of interleukin 2 and lymphokine-activated killer cells. Efficacy without significant toxicity.

Adoptive immunotherapy with high-dose interleukin 2 and lymphokine-activated killer (LAK) cells has proved to be successful in the treatment of some patients with metastatic cancer, but not without a significant degree of associated toxic effects. The primary goal of this study was to substantially reduce the toxicity of this complex and expensive treatment, while maintaining or improving efficacy. To this end, 29 patients were treated with LAK cells in conjunction with a low-dose regimen of interleukin 2 and a prolonged period of administration following LAK cell infusion. This protocol resulted in a considerable reduction in toxicity, as compared with that described in previous studies, without compromising the efficacy. This study offers further confirmation that adoptive immunotherapy of metastatic cancer can be clinically beneficial to patients for whom no other effective therapy is presently available.

Adult↗

Clinical factors influencing the efficacy of pooled platelet transfusions.

To determine the relative importance of clinical factors on the efficacy of platelet transfusions, 941 pooled platelet transfusions from HLA-unmatched donors were studied prospectively in 133 patients with bone marrow failure. Multiple linear regression analyses identified the major factors influencing one-hour-corrected increments (CI) as prior splenectomy, bone marrow transplantation, disseminated intravascular coagulation, concurrent intravenous amphotericin B, splenomegaly, and HLA antibody grade. The relative impact of these factors on CI has been quantitated by using a formula developed from these data. A linear relationship was demonstrated between increasing percentage of HLA antibody grade and decreasing CI. A number of other factors were less important in the linear regression model than the aforementioned major factors. These included platelet-specific antibodies, concurrent antibacterial antibiotics, clinical bleeding grade, and temperature. Factors that did not influence CI included the number of prior platelet transfusions, prior granulocyte transfusions, prior red cell transfusions, infection, age, blood group, diagnosis, sex, pretransfusion platelet count, prior pregnancies, and concurrent antineoplastic drugs. This study identified major clinical factors that significantly influenced CI and were major causes of refractoriness to pooled platelet transfusions.

Antibodies↗

Binding and antibody blocking effects of intravenous IgG preparation on peripheral blood cells.

The mode of action of high dose intravenous gammaglobulin (IVGG) in idiopathic thrombocytopenic purpura (ITP) is controversial. This study used immunofluorescence techniques to investigate the possibility that IVGG binds to peripheral blood cells and that such binding blocks attachment of cell specific autoantibodies. IVGG bound to platelets, neutrophils, monocytes and lymphocytes. Erythrocytes appeared to bind only anti-A and anti-B present in the IVGG. Multimeric and monomeric fractions of IVGG also bound to these cells. However, F(ab')2 fragments of the IVGG reacted only weakly with platelets, neutrophils, monocytes and lymphocytes. Binding of IVGG to platelets and neutrophils did not prevent opsonization of these cells by monoclonal antibodies with specificities corresponding to those previously ascribed to platelet and neutrophil autoantibodies. This suggests that IVGG does not act by blocking attachment of autoantibodies to platelets in ITP.

Antibodies↗

Factitious sneezing.

We report a case of hysterical, intractable paroxysmal sneezing in an adolescent girl. The patient had been observed by two pediatricians, an allergist, an emergency room physician, and a chiropractor. She had been treated with antihistamines, epinephrine, corticosteroid nasal spray, and a 1-week course of an oral corticosteroid without improvement. She was referred for evaluation of an allergic etiology before continuing her workup with a computed tomographic head scan. The patient had been sneezing almost daily for 3 mo up to 2000 times a day. The patient did not sneeze at night. She had nasal congestion but no rhinorrhea or eye symptoms. She did not sneeze during the interview. The results of a physical examination were normal except for mild obesity. No organic cause was found. Most cases of intractable paroxysmal sneezing reported in the literature occur in adolescents and appear to have a psychogenic etiology. The problem was discussed with the child and parents, and psychologic therapy was recommended. Considerable decrease in sneezing subsequently occurred, but the parents credited this is further chiropractic therapy.

Adolescent↗

Immunology of streptokinase in human subjects.

Streptokinase is an effective thrombolytic agent used in various thrombotic diseases. Until recently, allergic reactions have not been well characterized. We report the clinical and immunologic correlations of three types of reactions to streptokinase (S) in man. These include IgE antibody to S which mediates anaphylaxis and immediate-type skin reactivity to S. This skin test may be predictive of those at risk for anaphylaxis. IgG antibody and S form antigen-antibody complexes which result in toxic immune complex disease including skin, renal and joint symptoms. This human response simulates the animal model of immune complex disease reported over two decades ago. Lymphocyte mediated reactions include local delayed cutaneous reactions with systemic malaise correlating with in vitro lymphocyte reactions to S. An immune response of rising IgE, immediate-type skin reactivity and rising IgG antibody occurred in two physicians volunteering for skin test analysis to S.

Anaphylaxis↗

Delayed-onset heparin-induced thrombocytopenia. A potentially malignant syndrome.

Delayed-onset thrombocytopenia developed in 12 patients while they were receiving either prophylactic or therapeutic heparin. Five of the patients had thrombocytopenia alone, and seven had thromboembolic complications which contributed to the death of one patient. These complications included deep venous thrombosis (four patients), pulmonary embolism (three patients), myocardial infarction (one patient), sagittal sinus thrombosis (one patient), and femoral artery occlusion (one patient). The diagnosis of heparin-induced thrombocytopenia was delayed for between one and 13 days after the initial complicating event. All patients had heparin-dependent platelet-aggregating factor in their plasma. The characteristics of the heparin-dependent platelet-aggregating reaction were the same in all patients, but the nadir of thrombocytopenia was lower in patients with delayed-onset heparin-induced thrombocytopenia and complicating thromboembolism. These findings highlight the necessity for early recognition of this syndrome and for the prompt withdrawal of heparin to prevent considerable patient morbidity.

Adult↗

A case of Hageman factor deficiency with myeloid leukaemia.

The co-existence of blastic transformation of chronic myeloid leukaemia and an isolated deficiency of coagulation factor XII (Hageman Factor), is reported. In the absence of any evidence of factor XII deficiency in the patient's siblings and children, it is uncertain if this represents an acquired factor XII deficiency due to myeloid leukaemia, or the coincidental occurrence of myeloid leukaemia with this autosomal recessive condition.

Blood Coagulation Disorders↗

Detection of HLA antibodies by platelet crossmatching techniques.

Thirty-seven monospecific HLA antibodies directed against all common HLA-A and -B loci and reactive by the microlymphocytotoxicity assay (LCT) were tested against platelets carrying the corresponding antigen by three platelet crossmatch methods, the platelet immunofluorescence test (PIFT), platelet enzyme-linked immunosorbent assay (P-ELISA), and platelet radioimmunoassay (P-RIA). Positive reactions were obtained with the PIFT in 67 percent, the P-ELISA in 41 percent, and the P-RIA in 49 percent of 85 cell-serum pairs. The same cell-serum combinations gave 49 percent positive reactions in the lymphocyte immunofluorescence test. Three multispecific HLA antisera were positive in nine of nine cell-serum combinations by all four methods. Thirteen transfusions were given to eight patients with known HLA antibodies. All donor-recipient pairs were LCT positive, six were PIFT positive, and seven were PIFT negative. Three of seven PIFT-negative and none of six PIFT-positive transfusions were successful. Thus, platelet crossmatching is less sensitive than the LCT for the detection of complement-binding monospecific HLA antibodies. The platelet crossmatch, however, is able to identify some potentially successful HLA-incompatible donors for patients with multispecific HLA antibodies and limited access to HLA-identical donors.

Antibodies↗

Evolution of patient care, education, and research in asthma by one academic team of investigators over 35 years: the Northwestern University Medical School Division of Allergy-Immunology experience (Part Two).

This report reviews approximately 35 years of patient care, teaching, and research an asthma in one academic unit at Northwestern University Medical School. Historical perspectives are summarized on the delivery of care for asthma, therapeutic regimens for asthma we believed in (and were wrong), and diagnosis and management in the last decade of this century. Particular problems, such as potentially fatal asthma and assessment and management of such problems, are discussed. Finally, certain aspects of our basic research programs and their relevance to asthma are briefly reviewed. Part One of this article appeared in the May-June issue of this journal.

Adrenal Cortex Hormones↗

Evolution of patient care, education, and research in asthma by one academic team of investigators over 35 years. The Northwestern University Medical School Division of Allergy-Immunology Experience: Part One.

This report reviews approximately 35 years of patient care, teaching, and research on asthma in one academic unit at Northwestern University Medical School. Historical perspectives are summarized on the delivery of care for asthma, therapeutic regimens for asthma we believed in (and were wrong), and diagnosis and management in the last decade of this century. Particular problems, such as potentially fatal asthma and assessment and management of such problems, are discussed. Finally, certain aspects of our basic research programs and their relevance to asthma are briefly reviewed. An outline of contents is shown in Table I.

Asthma↗