ABSTRACT
Alkylating agents have been the major group of chemotherapeutic agents associated with an increased incidence of secondary leukemias. In ovarian cancer alkylating agents have resulted in a lesser, although still increased, risk of secondary malignancies. This paper reports two cases of ovarian cancer treated with cisplatin and doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH), and the subsequent development of an acute nonlymphocytic leukemia and a preleukemia syndrome. This regimen does not contain alkylating agents, and has not been associated with leukemia in patients with ovarian cancer. In these two cases, abnormalities of chromosomes 5, 7, 11, and 17 are reported which have been shown to occur in therapy-related leukemia.
Subject(s)
Cisplatin/adverse effects , Doxorubicin/adverse effects , Leukemia, Myeloid, Acute/chemically induced , Ovarian Neoplasms/drug therapy , Preleukemia/chemically induced , Adenocarcinoma/drug therapy , Adult , Cisplatin/therapeutic use , Cystadenocarcinoma/drug therapy , Doxorubicin/therapeutic use , Endometriosis/drug therapy , Female , Humans , Middle Aged , SyndromeABSTRACT
A 70 year old male patient admitted for coronary bypass surgery presented with a procainamide-induced lupus syndrome. This syndrome included a LLAC with a positive IgM ACA titer as well as a factor XII inhibitor. These drug-induced inhibitors were superimposed upon the patient's congenital deficiency of factor XI. The methods used to identify these abnormalities are described together with the replacement therapy employed to cover the surgical procedure. The long-term withdrawal of procainamide was associated with correction of all coagulation abnormalities except the factor XI deficiency.
Subject(s)
Blood Coagulation Factors/immunology , Factor XI Deficiency/blood , Factor XII/antagonists & inhibitors , Lupus Erythematosus, Systemic/chemically induced , Procainamide/adverse effects , Aged , Blood Coagulation Factors/analysis , Blood Coagulation Tests , Coronary Artery Bypass , Humans , Lupus Coagulation Inhibitor , Lupus Erythematosus, Systemic/blood , Male , Procainamide/administration & dosageSubject(s)
Antibody Formation , Genes, Dominant , Genes , HLA Antigens/genetics , Streptococcus pyogenes/immunology , Antigens, Bacterial , Chromosome Mapping , Female , Genetic Linkage , Humans , MaleABSTRACT
Employing an in vitro blastogenesis model, evidence has been set forth for a major gene locus which controls response to a purified, extracellular antigen from group A streptococci. Response to this antigen is inherited in an autosomal dominant manner. Analysis of the data for linkage to HLA was done with the computer program LINKAS which can resolve pleiotropy from linkage and can detect and estimate recombination in the presence of etiological heterogeneity. Maximum likelihood estimation and likelihood ratio tests were used to assess the relative support for competing hypotheses. The results of this analysis indicate that at least two loci are involved in one of two ways: one locus that is closely linked to HLA and one locus that is unlinked; or a two-locus system of complementary alleles which are both tightly linked to HLA.
Subject(s)
Antigens, Bacterial/genetics , Genetic Linkage , Adolescent , Adult , Aged , Antigens, Bacterial/immunology , Child , Genes, MHC Class II , HLA Antigens , Humans , Lymphocyte Activation , Male , Middle Aged , Models, Genetic , Streptococcus pyogenesABSTRACT
A purified, extracellular protein, M. W. 17500, from group A streptococci was used in an in vitro model to study genetic aspects of immune responsiveness. Peripheral blood lymphocytes from members of eight nuclear families and one kindred of three generations were isolated and purified by F-icoll-Isopaque flotation and cultured together with varying concentrations of antigen. A summary measure of the antigen response data (measured as CPM) was constructed through a weighted regression analysis of response on dose. Commingling analysis of the standardized regression coefficients provided evidence for the existence of two underlaying distributions. Segregation analysis confirmed that response to this antigen is controlled by a major gene and is inherited in an autosomal dominant manner.
