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Sulfisoxazole-induced thrombocytopenic purpura: Immunologic mechanism as cause
VOLUME NUMBER
Abstracts
56 5
elicit factors I.hat inhibit interferon and may contribute to the severity of the disease and the abundant and prolonged shedding of virus. S. B.
Pharmacology, pathology
physiology,
and
Massive theophylline overdose: Rapid elimination by charcoal hemoperfusion Ehlers,
240:474,
S., Zaske,
D., and
Sawchuk,
R.:
J. A. M.
A.
lI178.
Charcoal hemoperfusion is an efficient means for removing many drugs and endogenous substances from the circulation. This method of treatment was successfully employed to treat a 4%year-old woman who had ingested about fifty 200-mg aminophylline tablets (8.5 gm of theophylline) and whose serum theophylline level was 190 pg/ml on admission. Various methods employed to treat her progressively worsening condition were of no avail. When persistent cardiac arrhythmias and atrioventricular dissociation and cardiac arrest occurred requiring external cardiac massage for 20 min, charcoal hemoperfusion was instituted. Within one hour her condition began to improve and the laboratory findings showed a drop in the platelet count from 269,000 to l7O,OOO/cu mm, the serum calcium from 9.0 to 6.5 mg/ml, and a drop in the serum theophylline level to 20 pgiml. The patient unfortunately suffered irreversible anoxic central nervous system damage probably secondary to the prolonged hypotension and cardiac arrest, a complication that perhaps could have been avoided by earlier institution of the charcoal hemoperfusion. H. F.
Delay in the development of the allergic response to metals following intratracheal instillation Parker, Immunol.
D., and 57:289,
Turk,
J. L.: Int.
Arch.
Allergy
Appl.
1978.
The present experiments were performed to observe the effect of the lntratracheal instillation of water-soluble metal sensitizers on the immune response in guinea pigs. lntratracheal intubation with the soluble metal salts potassium dichromate (K,Cr,07) and nickel sulfate (NiSOJ has been demonstrated to cause a marked delay in the development of delayed hypersensitivity to the specific agent. Two tenths ml of a 1% solution of KZCr20, or NiS04 in saline was instilled into the trachea of guinea pigs. These instillations were repeated three times, at a-day intervals for the first week. This was followed by a 9-day interval, after which the guinea pigs received another three doses at ‘-day intervals. Animals were sensitized to KzCr,07 and NiSO, 9 days after the final intubation. Control animals received intuba-
21
tions of saline without the metal. A delay in the development of sensitivity to K2Cr20, compared with that developing in animals receiving saline intubation was demonstrated in two experiments. In the first experiment all the controls were sensitive 2 wk after immunization. However. only 1 of 9 of the animals intubated with the specific metal salt was reactive at this time. Fifty percent of the animals were reactive 1 wk later. The maximum reactivity was not present until 7 wk after immunization. A similar but more intense delay in the development of sensitivity was demonstrated in the second experiment, in which 80% of the animals remained unresponsive up to 8 wk after immunization. Intubation with K2Cr20, produced no change in the development of sensitivity to NiSO, when compared with the saline control. This indicates that the phenomenon described is immunologically specific. As a result of these experiments it is suggested that absorption of water-soluble metal sensitizers via respiratory route may, under certain circumstances. induce a temporary state of unresponsiveness even to a powerful immunologic stimulus and may not necessarily act directly to produce a state of sensitivity. Moreover, this phenomenon is immunologically specific. More experiments therefore are needed to define the role of the respiratory tract as a portal of entry for sensitizers, especially in an industrial situation. V. Ilea
Miscellaneous
allergies
Sulfisoxazole-induced thrombocytopenic purpura: Immunologic mechanism as cause Hamilton,
H., and
239:2586.
1978.
Sheets,
R.:
J. A. M.
A.
There is presumptive evidence implicating a large number of drugs which can induce thrombocytopenic purpura on an immunologic basis, but of this number only quinidine, quinine, digitoxin, rifampin, apronalide, novobiocin, and stibophen have been shown by both in vivo and in vitro testing to have such an immunologic effect. The present study demonstrated that sulfisoxazole also can induce thrombocytic purpura on an immunologic basis. A young farmer who had been under treatment for brucellosis with sulfisoxazole, tetracycline, and streptomycin developed severe thrombocytopenic purpura. One hour following the first dose of sulfisoxazole and tetracycline, he felt weak and developed back and leg pain along with headache. Shortly thereafter he developed purpuric spots on his tongue and cheeks followed by epistaxis, humaturia, and bloody stools. On admission to the hospital there was extensive purpura with large ecchymosis into the skin and mucous membranes. The urine and stools were strongly positive for occult blood. The platelet count was l.OOO/cu mm, hemoglobin was 11.6 gm/dl, reticulocyte count was 4.7%. and the bone marrow showed hypercellularity with plentiful megakaryocytes. The brucella titer was I : 20,480. After a rapid recovery the patient was challenged separately
22 Abstracts with each of the drugs with which he had been treated. Sulfisoxazole alone caused a recurrence of the symptoms. Serum studies revealed the presence of a serum factor which caused platelet agglutination in the presence of sultisoxazole. Some cross reactions were noted with certain other sulfonamides, particularly with sulfamethoxypyridazine. The patient was presumed to have become sensitized to sulfonamides by drinking cow’s milk contaminated with the drug. The pathogenetic mechanism for the thrombocytopenia is believed to be one of platelet destruction since the marrow showed such large numbers of megakaryocytes. H. F.
Immunology Demonstration of antibodies to chlorphenothiazine derivatives Furuya, D., and Urasawa, S.: Int. Arch. Allergy Appl. Immunol. 57:22, 1978. Sera from psychiatric patients receiving chlorophenothiazine derivatives (CECP) exhibit specific hemagglutinin activity to phenothiazines (Ph). The authors demonstrated immune responses to Ph derivatives by detecting specific antibody in sera of patients on long-term Ph therapy utilizing the passive hemagglutination test (PHA) in which rabbit RBC coated with the various phenothiazines were used as indicator. Antibody to CECP was raised in rabbits by immunization with the hapten-BSA conjugate in Freund’s adjuvant, and titers measured by PHA of RBC coupled with CECP protein carrier. Inhibition tests using structurally related Ph, such as CECP, chlorpromazine (CPZ), prochlorperazine (PCPZ), and chlomipramine (CMP), and unrelated haptens bis-@-chlorphenyl)-acetic acid (DDA) and riboflavin (RF) indicate that the side chain as well as the nucleus of the haptens participate in determining the immunologic specificity of the reaction. Of the 18 sera from the patients on long-term Ph treatment, 12 had anti-CECP titers of greater than 1 : 8 on PHA testing. This PHA activity resided
J. ALLERGY
in the euglobulin specific.
CLIN. IMMUNOL. NOVEMBER 1978
portion of the antiserum and was PhD.S.
Inhibition of human complement components by Loxosceles reclusa venom Futrell, M., and Morgan, Appl. Immunol. 57:275,
N.: Int. Arch. Allergy 1978.
The authors studied the effect of venom from the brown recluse spider on human complement and found that it inactivates Cl-C7 in vitro. This may explain why the lesions induced by the bite of this insect are similar pathologically to those seen in the Arthus and Shwartzman reactions, which are known to involve the complement system. Venom was added to fresh human sera from healthy volunteers, as well as to fresh cord blood sera and complement components (Cl-C9) assayed. Other venom aliquots were added to partially purified complement components, and the activity of the single component was investigated. One phase of the experiment studied inactivation of complement via the alternate pathway-here factor B was removed by heating the serum to 56” C for 30 min. Venom addition to the various sera significantly reduced the CH,a within 30 min, with optimal reduction dependent on the ratio of whole venom to complement. Depression of factors C&C9 was only 10% (or less) following treatment with the venom. Most affected were factors Cl-C7 where reduction of 80% to 95% occurred following the addition of the venom. Optimum temperatures and incubation times were determined for each component. It was also demonstrated that C3 inactivation could be accomplished by venom in the absence of factor B. Immune hemolysis could be restored when large amounts of the component in question were added to the venom-complement component mixture before assaying the hemolytic levels. Further studies are being undertaken on the interaction between venom and serum factors other than complement. D. S.
Abstracts
56 5
elicit factors I.hat inhibit interferon and may contribute to the severity of the disease and the abundant and prolonged shedding of virus. S. B.
Pharmacology, pathology
physiology,
and
Massive theophylline overdose: Rapid elimination by charcoal hemoperfusion Ehlers,
240:474,
S., Zaske,
D., and
Sawchuk,
R.:
J. A. M.
A.
lI178.
Charcoal hemoperfusion is an efficient means for removing many drugs and endogenous substances from the circulation. This method of treatment was successfully employed to treat a 4%year-old woman who had ingested about fifty 200-mg aminophylline tablets (8.5 gm of theophylline) and whose serum theophylline level was 190 pg/ml on admission. Various methods employed to treat her progressively worsening condition were of no avail. When persistent cardiac arrhythmias and atrioventricular dissociation and cardiac arrest occurred requiring external cardiac massage for 20 min, charcoal hemoperfusion was instituted. Within one hour her condition began to improve and the laboratory findings showed a drop in the platelet count from 269,000 to l7O,OOO/cu mm, the serum calcium from 9.0 to 6.5 mg/ml, and a drop in the serum theophylline level to 20 pgiml. The patient unfortunately suffered irreversible anoxic central nervous system damage probably secondary to the prolonged hypotension and cardiac arrest, a complication that perhaps could have been avoided by earlier institution of the charcoal hemoperfusion. H. F.
Delay in the development of the allergic response to metals following intratracheal instillation Parker, Immunol.
D., and 57:289,
Turk,
J. L.: Int.
Arch.
Allergy
Appl.
1978.
The present experiments were performed to observe the effect of the lntratracheal instillation of water-soluble metal sensitizers on the immune response in guinea pigs. lntratracheal intubation with the soluble metal salts potassium dichromate (K,Cr,07) and nickel sulfate (NiSOJ has been demonstrated to cause a marked delay in the development of delayed hypersensitivity to the specific agent. Two tenths ml of a 1% solution of KZCr20, or NiS04 in saline was instilled into the trachea of guinea pigs. These instillations were repeated three times, at a-day intervals for the first week. This was followed by a 9-day interval, after which the guinea pigs received another three doses at ‘-day intervals. Animals were sensitized to KzCr,07 and NiSO, 9 days after the final intubation. Control animals received intuba-
21
tions of saline without the metal. A delay in the development of sensitivity to K2Cr20, compared with that developing in animals receiving saline intubation was demonstrated in two experiments. In the first experiment all the controls were sensitive 2 wk after immunization. However. only 1 of 9 of the animals intubated with the specific metal salt was reactive at this time. Fifty percent of the animals were reactive 1 wk later. The maximum reactivity was not present until 7 wk after immunization. A similar but more intense delay in the development of sensitivity was demonstrated in the second experiment, in which 80% of the animals remained unresponsive up to 8 wk after immunization. Intubation with K2Cr20, produced no change in the development of sensitivity to NiSO, when compared with the saline control. This indicates that the phenomenon described is immunologically specific. As a result of these experiments it is suggested that absorption of water-soluble metal sensitizers via respiratory route may, under certain circumstances. induce a temporary state of unresponsiveness even to a powerful immunologic stimulus and may not necessarily act directly to produce a state of sensitivity. Moreover, this phenomenon is immunologically specific. More experiments therefore are needed to define the role of the respiratory tract as a portal of entry for sensitizers, especially in an industrial situation. V. Ilea
Miscellaneous
allergies
Sulfisoxazole-induced thrombocytopenic purpura: Immunologic mechanism as cause Hamilton,
H., and
239:2586.
1978.
Sheets,
R.:
J. A. M.
A.
There is presumptive evidence implicating a large number of drugs which can induce thrombocytopenic purpura on an immunologic basis, but of this number only quinidine, quinine, digitoxin, rifampin, apronalide, novobiocin, and stibophen have been shown by both in vivo and in vitro testing to have such an immunologic effect. The present study demonstrated that sulfisoxazole also can induce thrombocytic purpura on an immunologic basis. A young farmer who had been under treatment for brucellosis with sulfisoxazole, tetracycline, and streptomycin developed severe thrombocytopenic purpura. One hour following the first dose of sulfisoxazole and tetracycline, he felt weak and developed back and leg pain along with headache. Shortly thereafter he developed purpuric spots on his tongue and cheeks followed by epistaxis, humaturia, and bloody stools. On admission to the hospital there was extensive purpura with large ecchymosis into the skin and mucous membranes. The urine and stools were strongly positive for occult blood. The platelet count was l.OOO/cu mm, hemoglobin was 11.6 gm/dl, reticulocyte count was 4.7%. and the bone marrow showed hypercellularity with plentiful megakaryocytes. The brucella titer was I : 20,480. After a rapid recovery the patient was challenged separately
22 Abstracts with each of the drugs with which he had been treated. Sulfisoxazole alone caused a recurrence of the symptoms. Serum studies revealed the presence of a serum factor which caused platelet agglutination in the presence of sultisoxazole. Some cross reactions were noted with certain other sulfonamides, particularly with sulfamethoxypyridazine. The patient was presumed to have become sensitized to sulfonamides by drinking cow’s milk contaminated with the drug. The pathogenetic mechanism for the thrombocytopenia is believed to be one of platelet destruction since the marrow showed such large numbers of megakaryocytes. H. F.
Immunology Demonstration of antibodies to chlorphenothiazine derivatives Furuya, D., and Urasawa, S.: Int. Arch. Allergy Appl. Immunol. 57:22, 1978. Sera from psychiatric patients receiving chlorophenothiazine derivatives (CECP) exhibit specific hemagglutinin activity to phenothiazines (Ph). The authors demonstrated immune responses to Ph derivatives by detecting specific antibody in sera of patients on long-term Ph therapy utilizing the passive hemagglutination test (PHA) in which rabbit RBC coated with the various phenothiazines were used as indicator. Antibody to CECP was raised in rabbits by immunization with the hapten-BSA conjugate in Freund’s adjuvant, and titers measured by PHA of RBC coupled with CECP protein carrier. Inhibition tests using structurally related Ph, such as CECP, chlorpromazine (CPZ), prochlorperazine (PCPZ), and chlomipramine (CMP), and unrelated haptens bis-@-chlorphenyl)-acetic acid (DDA) and riboflavin (RF) indicate that the side chain as well as the nucleus of the haptens participate in determining the immunologic specificity of the reaction. Of the 18 sera from the patients on long-term Ph treatment, 12 had anti-CECP titers of greater than 1 : 8 on PHA testing. This PHA activity resided
J. ALLERGY
in the euglobulin specific.
CLIN. IMMUNOL. NOVEMBER 1978
portion of the antiserum and was PhD.S.
Inhibition of human complement components by Loxosceles reclusa venom Futrell, M., and Morgan, Appl. Immunol. 57:275,
N.: Int. Arch. Allergy 1978.
The authors studied the effect of venom from the brown recluse spider on human complement and found that it inactivates Cl-C7 in vitro. This may explain why the lesions induced by the bite of this insect are similar pathologically to those seen in the Arthus and Shwartzman reactions, which are known to involve the complement system. Venom was added to fresh human sera from healthy volunteers, as well as to fresh cord blood sera and complement components (Cl-C9) assayed. Other venom aliquots were added to partially purified complement components, and the activity of the single component was investigated. One phase of the experiment studied inactivation of complement via the alternate pathway-here factor B was removed by heating the serum to 56” C for 30 min. Venom addition to the various sera significantly reduced the CH,a within 30 min, with optimal reduction dependent on the ratio of whole venom to complement. Depression of factors C&C9 was only 10% (or less) following treatment with the venom. Most affected were factors Cl-C7 where reduction of 80% to 95% occurred following the addition of the venom. Optimum temperatures and incubation times were determined for each component. It was also demonstrated that C3 inactivation could be accomplished by venom in the absence of factor B. Immune hemolysis could be restored when large amounts of the component in question were added to the venom-complement component mixture before assaying the hemolytic levels. Further studies are being undertaken on the interaction between venom and serum factors other than complement. D. S.