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P Spath

Publications and source records attributed to P Spath.

17 recordsLinked to original sources

Determinations of penicilloyl specific IgE antibodies for the evaluation of hypersensitivity against penicillin.

Results from skin tests and radioallergosorbent test (penicilloyl G and penicilloyl V) were compared in 76 patients with suspected penicillin hypersensitivity and in 22 control subjects without such clinical symptoms. The test results were also correlated to the clinical history of adverse reactions and to the levels of total serum IgE. The overall agreement between skin test and RAST results was 89% in the patient group. Two of the control subjects without symptoms were professionally employed with penicillin production; one of them had circulating IgE-antibodies and the other exhibited positive skin tests. The skin tests were more frequently positive than the RAST test. By means of skin titration some of the skin tests were demonstrated to be false positive. The discrepancy can also be explained by the fact that skin reactions also occur in other situations than IgE-mediated adverse reactions. Circulating IgE-antibodies were not found in any of 23 cases where adverse reactions appeared later than 24 h after the latest penicillin administration. It is concluded that the measurement of circulating IgE-antibodies is a valuable aid in the diagnosis of penicillin allergy.

Adolescent

[Immunomechanisms in drug-induced hemolytic anemias].

Among the acquired hemolytic anemias, drug-induced immune hemolytic anemias (IHA) play a significant role. Many different drugs are capable of causing IHA, alphamethyldopa and penicillins have been responsible for the greatest number of cases. For the majority of the other drugs single cases of IHA are reported. Drug-induced immune hemolysis may be mediated by different immune mechanisms including the immune cytotoxicity type (penicillins and cephalosporins) with predominantly extravascular hemolysis. Immune hemolysis of most other drugs is due to immune complexes formed by the drug and specific antibodies leading to intravascular hemolysis in the presence of complement activation. So far, the autoimmune type of IHA caused by alphamethyldopa is unexplained, serologically this form cannot be distinguished from warm antibody auto-IHA. The clinical importance of drug-induced IHA depends on the severity of anemia and the problem of diagnosis leading to adequate therapeutic measures. Only a small number of cases showing a positive direct antiglobulin (Coombs') test caused by drugs will develop IHA. Therefore this finding does not require absolutely withdrawal of the drug, but careful observation of the patient. The diagnosis of drug-induced IHA is necessary for its distinction from auto-IHA and other secondary IHA. The study of such IHA has great importance for the understanding of other drug-induced cytopenias and may give explanations of the pathogenetic mechanisms of yet unexplained autoimmune phenomena.

Anemia, Hemolytic, Autoimmune

[The radioactive antiglobulin (Coombs') test].

Weak red cell sensitization by hemolyzing antibodies may not be detected by the standard antiglobulin test. For the diagnosis of certain immune hemolytic anemias more sensitive methods are needed. Anti-IgG was purified as F(ab)2 by pepsin digestion and labelled with 125 I using the chloramine T method. 15 X 10(7) cells were washed and suspended in 0.1 ml of 6% albumin in saline. After incubation with 0.1 ml of 125 I-anti-IgG F(ab')2 for 30 minutes, the cells were washed and the uptake of radioactivity was counted using a gamma-counter. Standard cells were coated with a known concentration of an IgG anti-D preparation in the range of 50--1000 molecules per red cell. The sensitivity for the detection of red cell sensitization was at least 50 molecules per red cell. Because of varying binding ratios between the labelled anti-IgG reagent and different red cell antibodies the determination of the exact number of IgG molecules on the red cells is difficult. However, this very sensitive and reproducible method shows practical advantages in comparison with a complement fixation antibody consumption method with which corresponding results were obtained. Beside the evaluation of antiglobulin test negative autoimmune hemolytic anemias, this method may be applied for the determination of the specificity of weak red cell alloantibodies not detectable by standard blood bank procedures.

Anemia, Hemolytic, Autoimmune

[Penicillin-induced immunhaemolytic anaemia. In vitro studies using separated monocytes (author's transl)].

Under certain conditions human monocytes were able to bind and ingest red cell-antibody complexes in vitro. Using penicillincoated red cells and purified monocytes we investigated sera of patients with penicillin allergy. It was shown that sera containing IgG-antibodies against penicillin induced the binding of penicillin-coated red cells to isolated monocytes provided IgG-antibodies of high titer were present. Inhibition and absorption tests demonstrated the specificity of the reaction in terms of IgG-antibodies and the drug. Monocyte binding was also studied in respect to the cross reactivity of penicillin antibodies and cephalosporins. We concluded that antipenicillin-antibodies of the IgG-class were able to induce an immunphagocytosis in vitro, if the drug was present in the test system. The reaction was dependent on the amount of antibodies of the IgG-class.

Anemia, Hemolytic

[Clinical significance and problems of technique in the immunochemical determination of the third complement component C 3 (beta 1 C/beta 1 A protein) (author's transl)].

Immunochemical determination of the third complement (C) component C 3 as beta 1 C/beta 1 A protein has found extensive use in the clinical evaluation of immunopathological conditions. C 3 changes are associated with inborn C defects and acquired diseases. In the latter case, diminished C3 levels are of the greatest practical relevance. Reduced C 3 values are not necessarily due to "classical" antibody-mediated C activation, as in immune-complex diseases, but may be caused also by "alternative" pathway activation and decreased C 3 synthesis. In addition, important technique factors have to be considered in the evaluation of immunochemically-determined C 3 values. Since the antigenic pattern of C 3 changes during in vitro ageing, not only the state of conversion of C 3 in the sample and in the reference serum (standard), but above all, the specificity of the anti-C 3-serum plays an important role in critically influencing the total error of the method. In order to avoid this error C 3 can be determined as beta 1 C protein using a beta 1 C standard which is, however, not easily available. On the other hand, beta 1 A quantitation causes less problems since standard sera usually contain C 3 as beta 1 A portein. However, an incubation period of 7 days at + 37 degrees C is necessary for complete C 3 conversion. This undesirable time delay has not yet been satisfactorily overcome by in vitro acceleration of C 3 conversion using different substances.

Antibody Specificity

Critical role of the conversion of the third complement component C3 (beta 1C/beta 1A) for its immunochemical quantitation.

For the immunochemical quantitation of the third component of complement C3 the state of conversion of this protein in the sample and the reference serum has to be guarded. Antisera raised against C3 may show different antibody specificity for the antigenic pattern of the C3 proteins which change during proteolysis by activation and also by ageing. It is shown that anti-C3-sera gave differences from -17% to + 91% comparing fresh and aged aliquots of the same sera directly on the same immunodiffusion plate corresponding to a particular anti-C3-serum. The use of three different monospecific antisera directed against the A determinant of C3 seemed to give results with good correlation in respect to C3 conversion. Glass and polystyrene plastic tubes did not have a significantly different effect on the C3 values in respect to C3 conversion. The in vitro acceleration of C3 conversion by thrombin or an inulin-like polysaccharide did not give consistent results in this context.

Complement C3

C3 standards?

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Complement C3

Phagocytes and C4 in paraproteinaemia.

Immunological studies were performed on patients with multiple myeloma. A defect in polymorphonuclear leucocyte (PMN) function as evidenced by diminished adherence of these cells to nylon fibre columns was detected in 16, and low levels of the fourth component of complement (C4) were observed in 14, of the 26 patients studied. Twelve of the patients with low C4 exhibited the defect in PMN adhesiveness whereas only four of the 12 patients with normal C4 showed the defect. The PMN defect was not caused solely by the low C4, since PMNs from seven patients with hereditary angioedema, which is associated with low levels of C4, did not show the defect. The low C4 and defect in PMN adhesiveness occurred primarily in patients with IgG myeloma; all but one of the patients with IgA myeloma, macroglobulinaemia, or light chain disease were normal in both parameters. Results of skin window studies indicated that patients with the PMN defect also had a defect in the early PMN inflammatory response. The defect in PMN adhesiveness could be completely corrected by incubating the cells in normal plasma. Binding of the C4 to paraprotein could not be demonstrated, and C1 activation was found to be caused only by one of 10 isolated paraproteins studied. These studies indicate that patients with paraproteinaemia have immunological abnormalities in addition to low immunoglobulin levels and suggest that these abnormalities may be involved in the pathogenesis of the recurrent infections commonly associated with this disease.

Adult

Positive direct antiglobulin (Coombs') test caused by cephalexin administration in humans.

Of 71 patients showing a negative direct antiglobulin (Coombs') test (DAT) before administration of cephalexin (CEX) three developed a positive DAT after therapy with this drug (4 percent). No case of immunohemolytic anemia was observed. The sera of the patients with a positive DAT reacted with cephalothin-coated red cells producing high titers, with penicillin cells normal titers and with CEX cells low titers. Since the red cell eluates of these patients did not give significant reactions with red cells sensitized with CEX, cephalothin and penicillin, a nonimmunological mechanism for the development of the positive DAT in these patients has to be assumed.

Adolescent

[Behavior of the complement components C3 and C4, C-reactive protein and blood sedimentation rate for activity control in arthritis patients during thermo-hydrotherapy].

21 male patients suffering since years from classical rheumatoid arthritis were treated with daily thermal baths of 37 degrees Celsius temperature during a 3 week period. To control the activity of the rheumatoid inflammation we used the complement components C3 and C4, the C-reactive protein and the blood sedimentation rate. No changes in the different activity parameters could be found during the course of the treatment. Joint function improved significantly. Therefore the combined treatment of rheumatoid arthritis with physio- and pharmacotherapy is recommended.

Adult