Thromboxane release during pacing-induced angina.
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Angina Pectoris↗
Biomedical subjects
F W Verheugt
Publications and source records attributed to F W Verheugt.
Echocardiographic aspects of cardiac amyloidosis.
We report the M-mode and two-dimensional echocardiographic findings in a patient with familial amyloidosis. The diagnosis was made by the clinical picture and histologic evidence of amyloid in peripheral nerve biopsy. Though the patient had no clinical sign of heart failure, extensive involvement of the heart was demonstrated by echocardiography. M-mode echocardiography revealed increased right ventricular wall thickness in conjunction with symmetric increase in left ventricular wall thickness. On two-dimensional echocardiography, the entire interventricular septum and the papillary muscles were more dense than normal. These high density echoes had a "granular and sparkling" pattern. This case shows that cardiac amyloidosis can be diagnosed in the pre-clinical, asymptomatic state by M-mode and two-dimensional echocardiography. When symptomatic, confusion with constrictive pericarditis may be avoided non-invasively.
Adult↗
Baka, a new platelet-specific antigen involved in neonatal allo-immune thrombocytopenia.
A family is described in which the mother developed platelet-specific antibodies, not directed against the antigens of the Zw(PlA) or the Ko system. The antibodies were only detectable in the immumofluorescence test and the radioactive antiglobulin test on platelets, and proved to be mainly IgG1 antibodies, although weak IgM antibodies of the same specificity were also detected. By cross-absorption studies, investigation of the family and a small-scale population study, it appeared that the antibodies were directed against a new antigen which we have called Baka. The frequency of the Baka phenotype in the Dutch population was 90.76%, the calculated genotype frequency 0.696. The Baka phenotype was neither sex-linked nor, so far as evaluable, closely linked to other platelet, red-cell, granulocyte, or HLA groups. The first child of this mother died of neonatal thrombocytopenia, the second child was unaffected. During the second pregnancy, the titre of the antibodies did not rise. The platelets of this child were found not to carry the Baka antigen.
Antibody Formation↗
Granulocyte-specific alloantigen loss in chronic granulocytic leukaemia.
The granulocytes of 23 patients with chronic granulocytic leukaemia were examined in the indirect immunofluorescence test and some also in the microleucoagglutination test, with specific alloantisera against the NA1, NA2, NB1 and ND1 antigens and a specific granulocyte xenoantiserum. In 10 cases a complete loss of alloantigens was detected. In one patient a partial loss was found. A significant correlation was established between this loss and an accelerated activity (impending blast crisis) of the disease.
Epitopes↗
A family with allo-immune neonatal neutropenia: group-specific pathogenicity of maternal antibodies.
A family is presented, in which the mother developed strong neutrophil granulocyte-specific antibodies with the specificity anti-NA. The first and third children, both NA1-positive, suffered from severe transient neonatal neutropenia, but the second child, NA1-negative, did not. Anti-NA1 antibodies were detectable in the serum of one affected child and the antibody level was directly related to the extent of neutropenia. The incidence of granulocyte-specific antibodies in 198 pregnant women was determined and found to be low.
Agranulocytosis↗
Recognition of a non-HLA-ABC antigen present on B and T lymphocytes and monocytes only detectable with the indirect immunofluorescence test.
The serum of a 39-year-old male under long-term platelet transfusion therapy for hypoplastic anemia with thrombocytopenia was investigated for the presence of leukocyte and platelet antibodies after the patients had received platelet concentrates from more than 700 random donors. The serological studies of his serum revealed: (1) the absence of platelet-reactive antibodies; (2) the absence of agglutinating or cytotoxic antibodies against leukocytes; (3) the presence of at least two granulocyte-specific antibodies, one with the specificity anti-NA2 and the other with an undefined specificity, both only detectable by indirect immunofluorescence, and (4) the presence of cytotoxic-negative fluorescence-positive peripheral-blood-mononuclear-cell-reactive antibodies, not directed against HLA-A, B or C antigens. The significance and implications of these findings are briefly discussed.
Absorption↗
A simple immunofluorescence test for the detection of platelet antibodies.
Immunofluorescence tests on platelets have always been hampered by nonspecific fluorescence caused by non-immunological binding of plasma proteins to the platelet membrane. It was found that this could be easily overcome by fixation of the cells with paraformaldehyde (PFA). By using PFA-fixed platelets, a simple method for the detection of platelet antibodies, the platelet suspension immunofluorescence test (PSIFT) was developed. PFA fixation did not alter or inactivate the platelet antigens tested. Platelet-reactive antibodies detected specifically with the PSIFT included platelet-specific agglutinins of the IgM class, non-agglutinating platelet-specific antibodies of the IgG class, drug-dependent platelet antibodies, HLA antibodies, as well as anti-A and anti-B antibodies. The sensitivity of the new test was satisfactory, as was its reproducibility. Measurement of platelet immunofluorescence was possible in a continuous flow microfluorometer, making a principle, quantitation of platelet antibodies and antigens possible.
Antibodies↗
Autoimmune granulocytopenia: the detection of granulocyte autoantibodies with the immunofluorescence test.
Neutropenia may be caused by neutrophil autoantibodies. The detection of such antibodies has always been difficult. Recently, we developed a sensitive indirect immunofluorescence technique applicable to granulocytes which proved to be of value in the detection of granulocyte alloantibodies. We have now used this method to investigate the serum and cells of 29 patients with idiopathic or secondary neutropenia. In four patients neutrophil-antigen-specific autoantibodies were detected in the serum and the patient's own granulocytes showed direct fluorescence. Furthermore, differences in the immunoglobulin composition and the temperature of optimal activity of the autoantibodies were found. Direct fluorescence was also demonstrated with the granulocytes from five other neutropenic patients and with the granulocytes from five non-neutropenic patients mainly with infectious disease. However, no granulocyte antibodies could be eluted or shown to be present in the serum. This indicates that a positive direct granulocyte fluorescence test may not be considered as proof that autoantibodies are present.
Adult↗
The detection of granulocyte alloantibodies with an indirect immunofluorescence test.
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Fluorescent Antibody Technique↗
Serological, immunochemical and immuoncytological properties of granulocyte antibodies.
The immunochemical characteristics of granulocyte allo- and autoantibodies can easily be studied with indirect immunofluorescence techniques. The correlation of these properties with the serological behavior of the antibodies and the clinical condition in which they were found was studied. The investigations included the determination of immunoglobulin class, subclass, light-chain composition, as well as optimal temperature of activity. Complement fixation in vitro was also investigated. Striking differences were found between IgG and IgM antibodies in their serological properties, especially in the granulocytotoxicity and leukoagglutination tests at different temperatures. Differences in light-chain and IgG subclass compositions of the antibodies did not seem to play a role. In studying the distribution of granulocyte-specific antigens on normal granulocytes and granulocytes in all stages of development, it was found that, while NA1, NA2 and ND1 are present in the same quantity on the cells of an individual, the NB1 antigen is unequally distributed, both over ripe granulocytes and granulocyte precursors.
Agglutination Tests↗
The detection of granulocyte alloantibodies with an indirect immunofluorescence test.
An indirect immunofluorescence technique for the detection of alloantibodies against granulocytes was developed. A major problem was the unspecific fluorescence of granulocytes, due to unspecific adherence of immunoglobulins to the cell membrane. This could be suppressed by the prefixation of the granulocytes with paraformaldehyde. The developed test proved to be specific and sensitive and to have a high reproducibility. Strongly positive reactions were obtained with antisera containing granulocyte-specific agglutinins or granulocyte-cytotoxins, but also with some sera that did not react in either the agglutination or the cytotoxicity test. HLA antisera also gave positive reactions, but strong anti-A, anti-B or anti-D sera did not react. With this technique leucocyte antibodies can be detected in a higher percentage of patients with febrile transfusion reactions.
Cytotoxicity Tests, Immunologic↗
Chronic atrial fibrillation. Success of serial cardioversion therapy and safety of oral anticoagulation.
BACKGROUND: Serial electrical cardioversion is often used for treatment of atrial fibrillation, but its long-term efficacy has not been determined prospectively. OBJECTIVES: To determine the long-term success rate of the serial electrical cardioversion approach in patients with chronic atrial fibrillation, to identify factors that predict its success, and to assess the efficacy and safety of oral anticoagulation in these patients. METHODS: Patients with chronic (> 24 hours) atrial fibrillation received anticoagulant therapy for at least 4 weeks prior to electrical cardioversion. No prophylactic antiarrhythmic agent was given after the first shock. Relapses were managed by using repeated cardioversions, after which serial antiarrhythmic drug therapy was started. Treatment with anticoagulants was withdrawn after 4 weeks of sinus rhythm. RESULTS: Two hundred thirty-six patients were followed up for a mean +/- SD of 3.7 +/- 1.6 years. The actuarial cumulative percentages of patients who maintained sinus rhythm after serial cardioversion treatment was 42% and 27% after 1 and 4 years, respectively. Multivariate analysis showed that factors that were associated with failure of this approach included duration of atrial fibrillation that exceeded 36 months (risk ratio, 5.0; P < .001), poor exercise tolerance (functional class III; risk ratio, 1.8; P = .001), and age older than 56 years (risk ratio, 1.5; P = .04). The anticoagulation level (international normalized ratio, 2.4-4.8) was associated with an incidence of thromboembolic events and bleeding complications of 0.2% and 1.5%, respectively. CONCLUSIONS: Many patients with chronic atrial fibrillation failed to respond to the serial electrical cardioversion strategy. However, in younger patients with a fair exercise tolerance and a duration of atrial fibrillation shorter than 36 months, this approach may be worthwhile. In addition, thromboembolic events were infrequent in the patients who were subjected to this regimen.
Administration, Oral↗
Predictive value of two-dimensional echocardiographic and hemodynamic measurements on admission with acute myocardial infarction.
To identify high-risk patients with acute myocardial infarction, we compared admission values of two-dimensional echocardiography and hemodynamic monitoring. Left ventricular wall motion score (WMS), left ventricular stroke work index (LVSWI), and pulmonary capillary pressure (PCP) were obtained in 77 patients without clinical signs of heart failure. Progression into Killip grade 3 or 4 was found in 16 of 77 patients (21%) within 32 +/- 6 hours (mean +/- 1 standard deviation) after admission. Mean WMS, LVSWI, and PCP in those patients who developed severe pump failure were significantly different from those who did not: 13.4 +/- 4.9 versus 7.3 +/- 4, 30 +/- 4 versus 46 +/- 11 gm/m2, and 21 +/- 8 versus 12 +/- 6 mm Hg, respectively. Sensitivity of WMS of greater than 7 and LVSWI of less than 35 gm/m2 in predicting Killip grade 3 or 4 was 88% and 94%, specificity was 57% and 87%, positive predictive value was 35% and 65%, and negative predictive value was 95% and 98%. Sensitivity of PCP was low (50%). Early identification of patients developing myocardial rupture or reinfarction was limited by both methods. We conclude that echocardiographic examination on admission in patients with acute myocardial infarction provides an alternative approach for early identification of low-risk patients.
Adult↗
Warfarin for ischemic heart disease.
Oral anticoagulation is one of the oldest ways for preventing secondary ischemic heart disease. With the introduction of aspirin, and low-dose aspirin in particular, the interest in oral anticoagulants has diminished, given the inherent bleeding risk. This short review deals with the efficacy and safety of oral anticoagulation in treating ischemic heart disease compared to placebo and to low-dose aspirin. Also, the comparison of the combination of oral anticoagulants and aspirin to aspirin alone is made. After myocardial infarction, oral anticoagulation is far superior to placebo in preventing recurrent ischemic events, with a risk of major bleeding of 1 per 100 patient-years. Oral anticoagulation seems equivalent to aspirin after myocardial infarction, but shows the same excess bleeding. Clearly, aspirin is, therefore, preferable for this indication. Combination therapy with oral anticoagulants and aspirin seems superior to aspirin alone provided the international normalized ratio is kept over 2.0. Also, here bleeding occurs in 1 out of 100 patient-years and the risk must be weighed against the risk of recurrent ischemic events. In coronary angioplasty, warfarin given before intervention looks promising in one large trial, but when given after intervention it is not beneficial and leads to more bleeding. Long-term oral anticoagulation does not lead to better graft patency after coronary surgery, but in one large trial it did lead to a better rate of survival.
Anticoagulants↗
ND1, a new neutrophil granulocyte antigen.
The serum of 2 patients suffering from autoimmune neutrophil granulocytopenia contained autoantibodies that were directed against a new granulocyte-specific antigen. Genetic analysis showed that this new antigen was not correlated with the already known neutrophil antigens, NA1, NA2, NB1, NC1 or 9a. This was studied in a four-generation family. In the Dutch population the frequency of the antigen, tentatively called ND1, is 98.5% (n = 67), pointing to a gene frequency of 0.88.
Antigens↗