losartan-potassium and Leukopenia

Anemia and neutropenia are common complications of HIV infection. Antiretroviral therapy with zidovudine exacerbates bone marrow suppression by inhibiting proliferation of blood cell progenitor cells. In addition, treatment for opportunistic infections or malignancies can involve the use of myelosuppressive drugs. As a consequence, severe anemia and neutropenia can result, thereby limiting the utilization of antiretroviral drugs. Since antiretroviral therapy can increase survival, drugs that ameliorate myelosuppression are important adjuncts in the treatment of HIV-infected patients. Three hematopoietic growth factors are effective in the treatment of anemia or neutropenia. In four placebo-controlled trials, erythropoietin (EPO) at doses up to 600 U/kg/wk decreased mean transfusion requirements by 37%, increased mean hematocrit by 4.5% and corrected anemia in the majority of patients receiving zidovudine over a 12-week period. In a separate study, granulocyte colony-stimulating factor (G-CSF) corrected leukopenia and isolated neutrophil defects in 22 patients with AIDS without altering HIV expression. When erythropoietin was added to the regimen, combined G-CSF and EPO corrected both anemia and leukopenia and lessened subsequent zidovudine toxicity. Similarly, granulocyte macrophage-colony-stimulating factor (GM-CSF) corrected leukopenia and pre-existing neutrophil defects in patients with HIV infection. In controlled and uncontrolled trials, GM-CSF also appears to reduce toxicity from zidovudine, ganciclovir, and antineoplastic therapy. New combinations of hematopoietic stimulants are being used to decrease the toxicity from combination antiretroviral therapy with alpha interferon and cytotoxic chemotherapy in the treatment of AIDS-related malignancies.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anemia; Antiviral Agents; Drug Therapy, Combination; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Cell Growth Factors; HIV Infections; Humans; Leukopenia; Zidovudine

Topics: Animals; Colony-Stimulating Factors; Erythropoietin; Growth Substances; Hematopoiesis; Hematopoietic Cell Growth Factors; Humans; Leukemia, Myeloid; Leukopenia; Mice; Myelodysplastic Syndromes; Recombinant Proteins

Topics: Adrenal Cortex Hormones; Alpha-Globulins; Androgens; Anemia, Aplastic; Animals; Base Sequence; Blood Proteins; Cell Division; Chemical Phenomena; Chemistry; Dogs; Drug Synergism; Endocrine Glands; Erythropoiesis; Erythropoietin; Glycoproteins; Hematopoiesis; Humans; Kidney; Leukocytes; Leukocytosis; Leukopenia; Mice; Polycythemia; Polycythemia Vera; Radiation Effects; Rats; Thrombopoietin; Thyroid Hormones

To compare the number and volume of red blood cell transfusions (RBCTs) in very low birth weight infants under restrictive red blood cell transfusion guidelines with and without erythropoietin administration.. In a controlled clinical trial conducted at the neonatal intensive care unit of Alzahra Hospital, Isfahan, Iran, between April 2002 to April 2004, 60 premature infants with gestational age up to 34 weeks, birth weight up to 1500 g, and postnatal age between 8 and 14 days were included. The newborns were randomized into 2 groups: Group 1 received 3 doses of 400 IU/kg erythropoietin per week for 6 weeks, and Group 2 received no treatment aside from their conventional medications.. The 2 groups did not differ significantly with respect to their mean gestational age, birth weight and hematocrit at the study entry. Fewer transfusions were administered to those receiving erythropoietin (26.7% versus 50%, p=0.03), but there was no statistically significant difference between groups with respect to volume of transfusion. Compared with the placebo group, the infants receiving erythropoietin had a higher mean hematocrit (34% +/- 4.3 versus 29% +/- 5.9, p<0.001) and absolute reticulocyte count (57 +/- 19 versus 10 +/- 4.8 x 106, p<0.001) at the end of the study. We found no significant difference in the incidence of thrombocytopenia and leukopenia between the 2 groups.. We conclude that when the restrictive RBCT guidelines were followed, treatment with erythropoietin can be useful in reduction of the number of RBCTs.

Topics: Erythrocyte Transfusion; Erythropoietin; Hematocrit; Humans; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Iran; Leukopenia; Practice Guidelines as Topic; Recombinant Proteins; Thrombocytopenia

To determine a recommended dose of once-weekly epoetin-beta administration for anemic cancer patients receiving myelosuppressive chemotherapy, we conducted a multicenter, randomized, double-blind trial.. A total of 86 patients with malignant lymphoma or lung cancer who received chemotherapy containing platinum, taxanes or anthracyclines were enrolled in the study. Patients were randomly assigned into groups that received three dose levels of epoetin-beta (9000, 18,000 or 36,000 IU) administered subcutaneously once a week for 12 weeks. The primary endpoint was change in hemoglobin, while the secondary endpoints were quality of life (QOL) assessed by Functional Assessment of Cancer Therapy-Anemia (FACT-An) questionnaire and transfusion requirements.. Among the 69 patients (per protocol set population) assessable for efficacy, hemoglobin level change in the 36,000 IU group was significantly greater than that in the 9000 IU group (1.75 +/- 2.15 versus 0.04 +/- 1.98 g/dl; P = 0.009), and a significant dose-response relationship was observed for the change in hemoglobin level (P = 0.003). Although changes in FACT-An Total Fatigue subscale (Fatigue subscale) scores were similar for the three dosage groups, there was a statistically significant correlation (r = 0.435, P < 0.001) between the change in hemoglobin levels and the change in Fatigue subscale scores. The proportion of transfused patients was significantly smaller in the 36 000 IU group compared with that in the 9000 IU group (P = 0.022, not adjusted for pre-study transfusions). The incidence of adverse events was similar in the three dosage groups.. Once-weekly epoetin-beta 36,000 IU for 12 weeks was well tolerated and significantly increased hemoglobin levels in anemic cancer patients receiving chemotherapy.

Topics: Adult; Aged; Anemia; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Erythrocyte Transfusion; Erythropoietin; Female; Hemoglobins; Humans; Leukopenia; Lung Neoplasms; Lymphoma; Male; Middle Aged; Platinum Compounds; Quality of Life; Recombinant Proteins; Taxoids

Paclitaxel and vinorelbine combination in previous untreated patients with stage IIIb-IV non-small cell lung cancer (NSCLC) as a phase II study.. Thirty-four patients (4 patients with stage IIIb, 30 patients in stage IV), with median age 66 and performance status 0-1, were administered paclitaxel, 175 mg/m(2) in a 3-h infusion rate on day 1 and vinorelbine, 25 mg/m(2) in a 10-min infusion rate on days 1, and 8 with G-CSF and EPO support.. Among our 33 evaluable patients for toxicity 16 patients (48.4%) presented leukopenia and 15 patients (45.4%) presented anemia despite G-CSF and EPO administration. Two patients (6%) presented Grade III-IV peripheral neuropathy. The overall response rate was 67.7%; 5 patients (16.1%) showed complete response (2 patients stage IIIb) and 16 patients (51.6%) showed partial response (1 patient stage IIIb). The overall median survival time was 10 months (range 3-18 months) and the median disease-free survival was 9 months (range 3-15 months) with an 1-year survival time of 45.1% (14 patients).. The results of the combination as 1st line treatment for patients with non-operable NSCLC are promising and should be further investigated.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Humans; Infusions, Intravenous; Leukopenia; Lung Neoplasms; Male; Middle Aged; Paclitaxel; Treatment Outcome; Vinblastine; Vinorelbine

We investigated subpopulations of T lymphocytes, NK cell number and cytotoxic activity in 14 chronic uremic patients on regular hemodialysis treatment. We observed a significantly decreased absolute lymphocyte number and percentage of CD3 cells. Relative numbers of CD16 cells were significantly elevated, but NK cell cytotoxic activity was within a normal range. Nine patients with chronic renal anemia on maintenance hemodialysis were enrolled in rHu-EPO treatment trial. The treatment was continued till the hematocrit level reached 30%. Each of the patients had corrected anemia and well-being. After 12 weeks of the treatment we observed in these patients decreases in CD3, CD4, CD8 and CD16 cell numbers and elevation of CD4/CD8 ratio. Cytotoxic activity of NK cells did not change significantly. Presented results indicate that chronic hemodialysis patients have significantly diminished lymphocyte number. rHu EPO treatment affects the T lymphocyte subsets inducing a deep decrease of CD8 and CD16 cell percentage leading to normalisation of the CD4/CD8 ratio.

Topics: Adolescent; Adult; Antigens, Differentiation, T-Lymphocyte; Cytotoxicity, Immunologic; Erythropoietin; Female; Humans; Killer Cells, Natural; Leukocyte Count; Leukopenia; Male; Renal Dialysis; T-Lymphocyte Subsets; Uremia

Exposure to high-dose radiation results in detrimental effects on survival. The effects of combined trauma, such as radiation in combination with hemorrhage, the typical injury of victims exposed to a radiation blast, on survival and hematopoietic effects have yet to be understood. The purpose of this study was to evaluate the effects of radiation injury (RI) combined with hemorrhage (i.e., combined injury, CI) on survival and hematopoietic effects, and to investigate whether hemorrhage (Hemo) enhanced RI-induced mortality and hematopoietic syndrome. Male CD2F1 mice (10 weeks old) were given one single exposure of γ- radiation (60Co) at various doses (0.6 Gy/min). Within 2 hr after RI, animals under anesthesia were bled 0% (Sham) or 20% (Hemo) of total blood volume via the submandibular vein. In these mice, Hemo reduced the LD50/30 for 30-day survival from 9.1 Gy (RI) to 8.75 Gy (CI) with a DMF of 1.046. RI resulted in leukocytopenia, thrombopenia, erythropenia, and bone marrow cell depletion, but decreased the caspase-3 activation response. RI increased IL-1β, IL-6, IL-17A, and TNF-α concentrations in serum, bone marrow, ileum, spleen, and kidney. Some of these adverse alterations were magnified by CI. Erythropoietin production was increased in kidney and blood more after CI than RI. Furthermore, CI altered the global miRNAs expression in kidney and the ingenuity pathway analysis showed that miRNAs viz., let-7e, miR-30e and miR-29b that were associated with hematopoiesis and inflammation. This study provides preliminary evidence that non-lethal Hemo exacerbates RI-induced mortality and cell losses associated with high-dose γ-radiation. We identified some of the initial changes occurring due to CI which may have facilitated in worsening the injury and hampering the recovery of animals ultimately resulting in higher mortality.

Topics: Anemia; Animals; Body Weight; Bone Marrow Cells; Caspase 3; Cytokines; Disease-Free Survival; Erythropoietin; Hematopoiesis; Hemorrhage; Inflammation; Kidney; Lethal Dose 50; Leukopenia; Male; Mice; MicroRNAs; NF-kappa B; Radiation Injuries; Thrombocytopenia; Water

The DEAH helicase RHAU (alias DHX36, G4R1) is the only helicase shown to have G-quadruplex (G4)-RNA resolvase activity and the major source of G4-DNA resolvase activity. Previous report showed RHAU mRNA expression to be elevated in human lymphoid and CD34(+) BM cells, suggesting a potential role in hematopoiesis. Here, we generated a conditional knockout of the RHAU gene in mice. Germ line deletion of RHAU led to embryonic lethality. We then targeted the RHAU gene specifically in the hematopoiesis system, using a Cre-inducible system in which an optimized variant of Cre recombinase was expressed under the control of the Vav1 promoter. RHAU deletion in hematopoietic system caused hemolytic anemia and differentiation defect at the proerythroblast stage. The partial differentiation block of proerythroblasts was because of a proliferation defect. Transcriptome analysis of RHAU knockout proerythroblasts showed that a statistically significant portion of the deregulated genes contain G4 motifs in their promoters. This suggests that RHAU may play a role in the regulation of gene expression that relies on its G4 resolvase activity.

Topics: Anemia, Hemolytic, Congenital; Animals; Bone Marrow Transplantation; Cell Cycle; Crosses, Genetic; DEAD-box RNA Helicases; Embryonic Development; Erythroblasts; Erythropoietin; Genes, Lethal; Genes, Synthetic; Green Fluorescent Proteins; Hematopoiesis; Leukopenia; Mice; Mice, Inbred C57BL; Mice, Knockout; Promoter Regions, Genetic; Protein Folding; Proto-Oncogene Proteins c-vav; Radiation Chimera; Recombinases; Thrombocytopenia

OBJECTIVE To explore the effect of combined use of rehmannia (RM) and rhodiola (RD) on peripheral leukopenia and bone marrow hematopoietic function suppression induced by cyclophosphamide (CTX) in mice.. ICR mice were established into bone marrow inhibition models by intraperitoneal injection of CTX, and were administered with RM, RD or its extract (RDE), singly or in mixture, via gastrogavage for 10 days. The changes of peripheral hemogram, bone marrow nucleated cell proliferation, CFU-GM colony formation, GM-CSF and erythropoietin (EPO) secretion were observed.. Compared with the un-treated model mice, the peripheral white blood cell count was significantly higher in model mice treated with RDE and RM mixture; the bone marrow nucleated cells count, CFU-GM formation, and GM-CSF production were significant higher in model mice treated with RD and RM mixture, showing statistical significance (P < 0.01); while EPO production in the RD and RM mixture treated group was slightly elevated, but the difference showed no statistical significance.. RD and RM mixture could regulate hematopoietic system by promoting the production of bone marrow cells and colonies, as well as enhancing the synthesis of related cytokines, such as GM-CSF, so as to increase the amount of peripheral white blood cells and restore the hematopoietic function of organism.

Topics: Animals; Bone Marrow; Cyclophosphamide; Drug Therapy, Combination; Drugs, Chinese Herbal; Erythropoietin; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoiesis; Leukopenia; Male; Mice; Mice, Inbred ICR; Phytotherapy; Rehmannia; Rhodiola

Topics: Aged; Aged, 80 and over; Anemia; Biopsy; Bone Marrow; Cell Nucleus; Diagnosis, Differential; Epoetin Alfa; Erythropoietin; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Leukopenia; Multiple Myeloma; Recombinant Proteins

Topics: Animals; Cell Adhesion; Cell Adhesion Molecules; Erythropoietin; Humans; Leukocyte Count; Leukocytes; Leukopenia; Microcirculation; Organotechnetium Compounds; Oximes; Rats; Recombinant Proteins; Technetium Tc 99m Exametazime

Evaluation of pharmacologic agents that stimulate fetal hemoglobin production has been done mainly in baboons and macaques. We investigated whether results in transgenic mice can predict the stimulation of fetal hemoglobin in primates, by testing gamma globin induction in response to a new ribonucleotide reductase inhibitor, Didox. A transgenic mouse line carrying the human A gamma gene linked to a locus control region cassette was used. Treatment of transgenic mice with Didox resulted in induction of gamma gene expression as documented by an increase in F reticulocytes and F cells and an elevation of gamma/gamma + beta biosynthetic ratio. Similarly, administration of Didox to a baboon in the nonanemic and chronically anemic state resulted in induction of gamma gene expression as shown by increases in F reticulocytes, F cells, and Hb F. These results suggest that the muLCR-A gamma transgenic mice can be used to screen new pharmacologic compounds for gamma globin inducibility.

Topics: Anemia; Animals; Chemical and Drug Induced Liver Injury; Erythropoietin; Fetal Hemoglobin; Gene Expression; Humans; Hydroxamic Acids; Leukopenia; Mice; Mice, Transgenic; Recombinant Proteins; Reticulocytes; Ribonucleotide Reductases; Thrombocytopenia

When 15-deoxyspergualin (DSG), a potent immunosuppressant, was administered into [BALB/c-->C3H/He] bone marrow chimeras from day 14 to day 25, increased thrombopoiesis was induced on day 20 to day 33, accompanied by marked leukocytopenia and anemia. The mean platelet counts in DSG-treated and control [BALB/c-->C3H/He] bone marrow chimeras on day 25 were (114.1 +/- 0.5) x 10(4)/microliter versus (58.6 +/- 2.6) x 10(4)/microliter (1.9-fold increase). Colony-forming units-megakaryocyte (CFU-Meg) were not significantly increased in DSG-treated bone marrow chimeras. Colony-forming units-granulocyte/macrophage (CFU-GM) and burst-forming units-erythroid (BFU-E) were decreased during DSG-treatment whereas CFU-Mix colony formations were rather increased, and more primitive hematopoietic progenitor cells (highly proliferative potential colony-forming units [CFU-HPP]) were not decreased in the same time period. Since CFU-GM and BFU-E colony formations were increased immediately after the cessation of DSG treatment, followed by the rebound of leukocyte counts and the recovery of hemoglobin (Hb) levels, the leukocytopenia and anemia appeared to be induced by a cytostatic effect of DSG. The adverse effect of DSG was partly reversed by the simultaneous administration of granulocyte colony-stimulating factor (G-CSF) and/or erythropoietin (EPO), suggesting the need for the administration of these cytokines in the case of bone marrow transplants treated with DSG. Furthermore, it was of note that DSG modulated hematopoiesis and stimulated the production of thrombopoietin (TPO)-like cytokine(s) as well as interleukin-3 (IL-3).

Topics: Anemia; Animals; Blood Cell Count; Blood Platelets; Bone Marrow Transplantation; Erythropoietin; Granulocyte Colony-Stimulating Factor; Guanidines; Hematopoiesis; Immunosuppressive Agents; Interleukin-3; Leukopenia; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Thrombopoietin; Transplantation Chimera

Topics: Anemia; Blood Platelets; Erythropoiesis; Erythropoietin; Humans; Kidney Failure, Chronic; Leukopenia; Recombinant Proteins; Renal Dialysis; Thrombocytopenia

Topics: Anemia; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Cell Growth Factors; Hematopoietic Stem Cells; Humans; Interleukins; Leukopenia; Thrombocytopenia

Zidovudine is now used extensively in an effort to control infection with the human immunodeficiency virus (HIV). The drug is associated with major hematologic toxicity, especially anemia and granulocytopenia. Conservative management of hematologic toxicity includes dosage reduction or cessation of therapy, diagnosis and treatment of chronic debilitating diseases, and supportive care, such as blood transfusions. New investigational agents, including hematopoietic growth factors, are being studied to combat the toxicities associated with zidovudine. The efficacy of these agents has yet to be established. Recent advances in drug efficacy at reduced dosage and in combination therapy promise to permit use of zidovudine with markedly reduced toxicity.

Topics: Acquired Immunodeficiency Syndrome; Anemia; Colony-Stimulating Factors; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Growth Substances; Humans; Leukopenia; Recombinant Proteins; Zidovudine

A spontaneous oscillation of the white blood cell count was observed in a 58 year old man with chronic myelogenous leukemia (CML). Similar cyclic variations were noted in the platelet and reticulocyte counts with no apparent alterations in marrow cellularity to account for such changes. Since direct correlation was noted between white blood cells, platelets, and reticulocyte counts versus spleen size, it suggests that splenic hemopoiesis may be responsible for these cyclic changes. A possible inverse relationship between colony-stimulating factor (CSF) activity and the white blood cell count was noted, suggesting that CSF may be the humoral agent controlling granulocyte production. A direct correlation between the white blood cell count and serum unsaturated vitamin B12 binding capacity (UBBC) and lysozyme was also noted and further supports the concept that the latter two are measures of the granulocyte pool and metabolism. An inverse relationship between CSF activity and the UBBC suggests that these may be two different entities. Finally a modified form of standard chemotherapy may be effective in inducing remission in cases of CML with marked cyclic leukocytosis-leukopenia.

Topics: Alkaline Phosphatase; Blood Cell Count; Blood Platelets; Bone Marrow Examination; Colony-Stimulating Factors; Erythropoietin; Hemoglobins; Humans; Karyotyping; Leukemia, Myeloid; Leukocyte Count; Leukocytosis; Leukopenia; Male; Middle Aged; Muramidase; Periodicity; Reticulocytes; Spleen; Vitamin B 12

Topics: Anemia; Animals; Autopsy; Bone Marrow Cells; Bone Marrow Transplantation; Erythropoiesis; Erythropoietin; Escherichia coli; Female; Haplorhini; Hematoma; Hematopoiesis; Hemorrhage; Iron Radioisotopes; Leukocyte Count; Leukocytes; Leukocytosis; Leukopenia; Macaca; Male; Mice; Nandrolone; Nitrogen Mustard Compounds; Polysaccharides, Bacterial; Radiation Injuries, Experimental; Time Factors; Transplantation, Autologous

Topics: Anemia; Animals; Bone Marrow Examination; Castration; Disease Models, Animal; Erythrocyte Aging; Erythrocyte Count; Erythropoietin; Estrogens; Female; Hematocrit; Hematologic Diseases; Hemoglobinometry; Homozygote; Leukocyte Count; Leukopenia; Male; Rats; Rodent Diseases; Sex Factors; Spleen; Splenectomy; Splenomegaly

Topics: Animals; Bone Marrow; Bone Marrow Cells; Dogs; Erythropoiesis; Erythropoietin; Hematopoiesis; Hematopoietic System; Humans; Leukocytes; Leukopenia; Rats; Reticulocytes