losartan-potassium and Sarcoma--Kaposi

Human immunodeficiency virus (HIV) infection is associated with multiple defects in immune regulation and hematopoiesis. These defects include decreased proliferation of hematopoietic progenitor cells and increased destruction of mature cells. There are also disturbances of regulatory cytokines. As a result, hematopoietic cytopenias are common and the tolerance of myelosuppressive therapy is poor. One successful approach to the management of these clinical problems is the use of hematopoietic growth factors. To date, three agents have been studied in patients with HIV infection. In a Phase I trial, granulocyte macrophage-colony stimulating factor (GM-CSF) corrected leukopenia and pre-existing neutrophil defects in patients with HIV infection. In uncontrolled trials, GM-CSF also appears to reduce toxicity from zidovudine, ganciclovir, alpha-interferon, and antineoplastic therapy. In a placebo-controlled trial, erythropoietin (EPO) decreased transfusion requirements and corrected anemia in the majority of patients receiving zidovudine. In a Phase I/II trial, granulocyte colony-stimulating factor (G-CSF) also corrected leukopenia and neutrophil defects in patients with AIDS without altering HIV expression. Combined G-CSF and EPO treatment corrected both anemia and leukopenia and reduced zidovudine toxicity. New combinations of hematopoietic stimulants are being used to decrease the toxicity from cytotoxic chemotherapy in the treatment of AIDS-related malignancies. Future treatments with other recombinant cytokines may result in both reduction in myelosuppression from drug therapy and, possibly, reconstitution of the immune and hematopoietic systems of HIV-infected patients.

Topics: Acquired Immunodeficiency Syndrome; Bone Marrow; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Lymphoma, Non-Hodgkin; Sarcoma, Kaposi; Zidovudine

Three hematopoietic stimulants have been used in patients with HIV infection and a variety of AIDS-related complications. Both G-CSF and GM-CSF have demonstrated the ability to correct leukopenia related to HIV infection and ameliorate the drug-related myelosuppressive effects of zidovudine, trimethoprim/sulfamethoxazole, ganciclovir, and, in the case of GM-CSF, alpha-interferon, and cancer chemotherapies. Erythropoietin has been successfully used to ameliorate the anemia associated with HIV infection and zidovudine therapy. Treatment with these hematopoietic stimulants is very well tolerated with minimal toxicity. Of the granulocyte stimulants, G-CSF appears to induce fewer side effects than GM-CSF in trials conducted to date. Future trials demonstrating that the amelioration of hematopoietic suppression by the colony-stimulating factors results in increased clinical response rates and improved survival are necessary to fully assess the value of this approach in the care of HIV-infected patients.

Topics: Acquired Immunodeficiency Syndrome; Drug Therapy, Combination; Erythropoietin; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Cell Growth Factors; HIV Infections; Humans; Lymphoma, Non-Hodgkin; Sarcoma, Kaposi; Zidovudine

Erythropoietin (EPO) is commonly used to treat anemias secondary to renal failure, malignancy, and AIDS. Although therapeutic complications are well described, overdose is rare. A 42-y-o man with AIDS confused his instructions for self-administration of interferon and EPO and began injecting himself daily with 10,000 units of EPO for several weeks. He presented with confusion, pain in his abdomen and feet, and a hemoglobin of 23.2 g/dLwith a hematocrit of 77.1%. The patient was treated with iv fluids, phlebotomy and 2 sessions of erythropheresis which removed 898 mL and 640 mL of red blood cells, respectively; his hemoglobin remained between 12-14 g/dL and symptoms resolved. His only sequelae involved skin loss over his toes, which did not require grafting. This rare case of EPO overdose highlights the complications of essential erythrocytosis, with central nervous system, peripheral, and presumed mesenteric ischemia.

Topics: Acquired Immunodeficiency Syndrome; Adult; Cytapheresis; Diagnosis, Differential; Drug Overdose; Emergency Treatment; Erythropoietin; Humans; Male; Sarcoma, Kaposi

Three cases of adult pure red cell aplasia (PRCA) ARE REPORTED. All patients proved refractory to various combinations of androgens and corticosteroids. The first case, harboring a thymoma, showed a complete clinical remission following cyclophosphamide therapy. The second and third responded similarly to either a combined cyclophosphamide + antilymphocyte globulin (ALG) treatment or to ALG administration preceded by a small dosage of cyclophosphamide, which had proved ineffective when administered alone. Serum IgG inhibitors to erythropoiesis were demonstrated in all cases by means of in vivo and/or in vitro techniques. The inhibitor(s), although directed against the erythroid marrow in both the first and third patients (PRCA type A), apparently functioned as an antibody to circulating erythropoientin (Ep) in the second case (PRCA type B). The inhibitor(s) was always absent in postremission samples. Additionally, experimental models for both types of human PRCA were established in normal rodents. The present studies support the contention that adult PRCA is an autoimmune disease. The therapeutic role of cytotoxic-immunodepressive agents in PRCA patients is confirmed. It is emphasized that ALG may represent an additional therapeutic tool in cases resistant to cyclophosphamide and/or steroids. In addition, cyclophosphamide proved effective in a patient harboring a thymoma not amenable to surgery. Finally, it is postulated that IgG serum autoantibodies, directed against either an early erythroid precursor (PRCA type A) or, more rarely, circulating Ep (PRCA type B), play a major role in the pathogenesis of the disease.

Topics: Aged; Anemia, Aplastic; Antibodies, Antinuclear; Antilymphocyte Serum; Autoantibodies; Blood Transfusion; Bone Marrow Examination; Cyclophosphamide; Dexamethasone; Diabetic Coma; Erythrocytes; Erythropoietin; Female; Heart Failure; Hematocrit; Hepatitis; Humans; Immunoglobulin G; Iron; Male; Middle Aged; Radiography, Thoracic; Sarcoma, Kaposi; Serum Globulins; Skin Manifestations; Thymoma