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94 NORTH CAROLINA MEDICAL JOURNAL February, 1967 of scratch tests were again negative, he found that intradermal injection of a mixture of blood serum and aminopyrine produced strikingly positive results in three subjects and was followed by the full-blown disease in two. He therefore suggested a possible drug-protein linkage as the basis of the "allergic'' reaction. Because of the decline in the incidence of agranulocytosis which followed prohibition of over-the-counter sales in 1938, little research was carried out until the 1950s. At that time Brodie37 reported on the metabolism of aminopyrine. It was found that an orally administered dose was rapidly and essentially completely absorbed from the gastrointestinal tract, reaching a peak plasma level in two hours. Blood levels declined from 10% to 30% per hour, the drug and its metabolic products being excreted in the urine. Granulocytes disappear from the peripheral blood within one hour of administration of aminopyrine, with cellular destruction progressing from the most mature to the immature forms. Moeschlin and Wagner23 postulated that the combination of aminopyrine and a serum protein reacted to produce agglutination of the granulocytes, which were themselves destroyed in the lungs. This increased peripheral destruction would explain the characteristic progression of bone-marrow destruction. They felt, therefore, that the evidence was sufficiently strong to support the conclusion that amino-pyrine-induced agranulocytosis is in the nature of an antigen-antibody reaction. In 1955 Moeschlin20 reported that agglutination tests performed on the sera of patients with agranulocytosis consistently produced positive results with leukocyte suspensions from healthy controls. With the offending antigen thus located in the serum, the schema shown in Figure 2 was proposed. This development brought aminopyrine-induced agranulocytosis parallel with other immunocytopenias such as acquired hemolytic anemia and acquired idiopathic thrombocytopenic purpura. Moeschlin cautioned, however, that the combination of a chemical substance with the leukocyte might induce the body to produce an antibody directed not only against the above antigen but also 39 Drug + Protein 1 Antigen Sensitization antibodv formation Antibodv+ Leukocyte Ant igen Leukocyte Agglutination i Massive Peripheral Leukocyte destruction (lungs) i Release of Mature Marrow Granulocytes (myelocytic marrow) i Marrow Exhaustion (myeloblastic or reticular marrow) Figure 2. (From Gellis and Kagan:™) against the leukocyte. This, in a sense, would represent the formation of isoantibodies and place the disease in the category of an autoimmune phenomenon. In 1958 Halpern38 characterized the nature of the antigen-antibody response to aminopyrine as follows: 1) Circulating antibody can be demonstrated by passive transfer of the patient's serum into controls. 2) In passive dermal transfer, the reaction can be elicited by either oral or parenteral administration of aminopyrine but not by local injection at the site of the serum injection. 3) The antigen-antibody complex formed in vitro is labile and can be easily dissociated by simple dialysis. 4) The antibody is rapidly fixed on passive transfer and the reaction reaches the maximum as soon as two hours after the intradermal injection of the serum. 5> The antibody is thermolabile and is destroyed by heating for 30 minutes at 58 C. 6) The antibody migrates with the beta-1, gamma-1, gamma-2 globulin fraction. 7) It is likely that the antigen-antibody complex is formed with the chemical substance without any previous conjugation.
Object Description
Rating | |
Fixed Title * | NCHH-17: North Carolina Medical Journal [1940-Present] |
Document Title | North Carolina Medical Journal [1940-Present] |
Subject Topical Other | Public Health -- Periodicals.; Physicians -- North Carolina -- Directory.; Societies, Medical -- North Carolina -- Periodicals. |
Description | Includes Transactions of the Society, -1960; 1961- , Transactions issued separately, bound in.; Includes Transactions of the auxiliary to the Medical Society of the State of North Carolina and Proceedings of the North Carolina Public Health Association. Official organ of the Medical Society of the State of North Carolina, 1940-May 1972; of the North Carolina Medical Society, June 1972-. Vols. for 1940-May 1972 published by the Medical Society of the State of North Carolina; June 1972- by the North Carolina Medical Society. |
Contributor | Medical Society of the State of North Carolina. Transactions.; Medical Society of the State of North Carolina.; North Carolina Medical Society.; North Carolina Medical Society. Transactions.; North Carolina Public Health Association. Proceedings. |
Publisher | [Winston-Salem] : North Carolina Medical Society [etc.], 1940- |
Repository | University of North Carolina at Chapel Hill. Health Sciences Library. |
Host | University of North Carolina at Chapel Hill |
Date | 1967 |
Identifier | NCHH-17-028 |
Form General | Periodicals |
Language | English |
Rights | This item is part of the North Carolina History of Health Digital Collection. Some materials in the Collection are protected by U.S. copyright law. This item is presented by the Health Sciences Library of the University of North Carolina at Chapel Hill for research and educational purposes. It may not be republished or distributed without permission of the Health Sciences Library. |
Digital Collection | North Carolina History of Health Digital Collection |
Sponsor | The North Carolina History of Health Digital Collection is an open access publishing initiative of the Health Sciences Library of the University of North Carolina at Chapel Hill. Financial support for the initiative was provided in part by a multi-year NC ECHO (Exploring Cultural Heritage Online) digitization grant, awarded by the State Library of North Carolina, and funded through the Library Services and Technology Act (LSTA). |
Volume Number | 28 |
Health Discipline | Medicine |
Digital Format | JPEG 2000 |
Print / Download PDF Version | http://archives.hsl.unc.edu/nchh/nchh-17/nchh-17-028.pdf |
Document Sort | all; nchh-17 |
Volume Link | http://dc.lib.unc.edu/cdm/search/collection/nchh/field/identi/searchterm/NCHH-17-028 |
Title Link | http://dc.lib.unc.edu/cdm/search/collection/nchh/field/documa/searchterm/NCHH-17 |
Catalog Record link | http://search.lib.unc.edu/search?R=UNCb1306322 |
Revision History | done |
Description
Fixed Title * | Page 94 (image) |
Document Title | North Carolina Medical Journal [1940-Present] |
Subject Topical Other | Public Health -- Periodicals.; Physicians -- North Carolina -- Directory.; Societies, Medical -- North Carolina -- Periodicals. |
Description | Includes Transactions of the Society, -1960; 1961- , Transactions issued separately, bound in.; Includes Transactions of the auxiliary to the Medical Society of the State of North Carolina and Proceedings of the North Carolina Public Health Association. Official organ of the Medical Society of the State of North Carolina, 1940-May 1972; of the North Carolina Medical Society, June 1972-. Vols. for 1940-May 1972 published by the Medical Society of the State of North Carolina; June 1972- by the North Carolina Medical Society. |
Contributor | Medical Society of the State of North Carolina. Transactions.; Medical Society of the State of North Carolina.; North Carolina Medical Society.; North Carolina Medical Society. Transactions.; North Carolina Public Health Association. Proceedings. |
Publisher | [Winston-Salem] : North Carolina Medical Society [etc.], 1940- |
Repository | University of North Carolina at Chapel Hill. Health Sciences Library. |
Host | University of North Carolina at Chapel Hill |
Date | 1967 |
Identifier | NCHH-17-028-0182 |
Form General | Periodicals |
Page Type | all; all images; chart/table; article |
Language | English |
Rights | This item is part of the North Carolina History of Health Digital Collection. Some materials in the Collection are protected by U.S. copyright law. This item is presented by the Health Sciences Library of the University of North Carolina at Chapel Hill for research and educational purposes. It may not be republished or distributed without permission of the Health Sciences Library. |
Filename | ncarolinamed28v11967medi_0182.jp2 |
Digital Collection | North Carolina History of Health Digital Collection |
Sponsor | The North Carolina History of Health Digital Collection is an open access publishing initiative of the Health Sciences Library of the University of North Carolina at Chapel Hill. Financial support for the initiative was provided in part by a multi-year NC ECHO (Exploring Cultural Heritage Online) digitization grant, awarded by the State Library of North Carolina, and funded through the Library Services and Technology Act (LSTA). |
Volume Number | 28 |
Issue Number | 3 |
Page Number | 94 |
Health Discipline | Medicine |
Full Text | 94 NORTH CAROLINA MEDICAL JOURNAL February, 1967 of scratch tests were again negative, he found that intradermal injection of a mixture of blood serum and aminopyrine produced strikingly positive results in three subjects and was followed by the full-blown disease in two. He therefore suggested a possible drug-protein linkage as the basis of the "allergic'' reaction. Because of the decline in the incidence of agranulocytosis which followed prohibition of over-the-counter sales in 1938, little research was carried out until the 1950s. At that time Brodie37 reported on the metabolism of aminopyrine. It was found that an orally administered dose was rapidly and essentially completely absorbed from the gastrointestinal tract, reaching a peak plasma level in two hours. Blood levels declined from 10% to 30% per hour, the drug and its metabolic products being excreted in the urine. Granulocytes disappear from the peripheral blood within one hour of administration of aminopyrine, with cellular destruction progressing from the most mature to the immature forms. Moeschlin and Wagner23 postulated that the combination of aminopyrine and a serum protein reacted to produce agglutination of the granulocytes, which were themselves destroyed in the lungs. This increased peripheral destruction would explain the characteristic progression of bone-marrow destruction. They felt, therefore, that the evidence was sufficiently strong to support the conclusion that amino-pyrine-induced agranulocytosis is in the nature of an antigen-antibody reaction. In 1955 Moeschlin20 reported that agglutination tests performed on the sera of patients with agranulocytosis consistently produced positive results with leukocyte suspensions from healthy controls. With the offending antigen thus located in the serum, the schema shown in Figure 2 was proposed. This development brought aminopyrine-induced agranulocytosis parallel with other immunocytopenias such as acquired hemolytic anemia and acquired idiopathic thrombocytopenic purpura. Moeschlin cautioned, however, that the combination of a chemical substance with the leukocyte might induce the body to produce an antibody directed not only against the above antigen but also 39 Drug + Protein 1 Antigen Sensitization antibodv formation Antibodv+ Leukocyte Ant igen Leukocyte Agglutination i Massive Peripheral Leukocyte destruction (lungs) i Release of Mature Marrow Granulocytes (myelocytic marrow) i Marrow Exhaustion (myeloblastic or reticular marrow) Figure 2. (From Gellis and Kagan:™) against the leukocyte. This, in a sense, would represent the formation of isoantibodies and place the disease in the category of an autoimmune phenomenon. In 1958 Halpern38 characterized the nature of the antigen-antibody response to aminopyrine as follows: 1) Circulating antibody can be demonstrated by passive transfer of the patient's serum into controls. 2) In passive dermal transfer, the reaction can be elicited by either oral or parenteral administration of aminopyrine but not by local injection at the site of the serum injection. 3) The antigen-antibody complex formed in vitro is labile and can be easily dissociated by simple dialysis. 4) The antibody is rapidly fixed on passive transfer and the reaction reaches the maximum as soon as two hours after the intradermal injection of the serum. 5> The antibody is thermolabile and is destroyed by heating for 30 minutes at 58 C. 6) The antibody migrates with the beta-1, gamma-1, gamma-2 globulin fraction. 7) It is likely that the antigen-antibody complex is formed with the chemical substance without any previous conjugation. |
Digital Format | JPEG 2000 |
Print / Download PDF Version | http://archives.hsl.unc.edu/nchh/nchh-17/nchh-17-028.pdf |
Document Sort | all; nchh-17 |
Article Title | Aminopyrine And Agranulocytosis Review And Report Of Six Cases |
Article Author | Charles Fred Zernechel |
Volume Link | http://dc.lib.unc.edu/cdm/search/collection/nchh/field/identi/searchterm/NCHH-17-028 |
Title Link | http://dc.lib.unc.edu/cdm/search/collection/nchh/field/documa/searchterm/NCHH-17 |
Catalog Record link | http://search.lib.unc.edu/search?R=UNCb1306322 |
Revision History | done |
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