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[The protective activity of a new variant of the probiotic Acilact in exposure to ionizing radiation and anticancer chemotherapy under experimental conditions].

The aim of the study was to investigate the protective activity of a new variant of the probiotic Acilact in exposure to ionizing radiation and anticancer chemotherapy under experimental conditions. The study revealed protective effects of the preparation after combined exposure of mice to radiation and temperature. The preparation increased 30-day survival of the mice, inhibited intestinal colonization with gram-negative microorganisms, and increased resistance to LPS. A multidirectional protective effect of the probiotic was observed after the use of sublethal doses of radiation; this effect was manifested by quicker normalization of hematological parameters and bone marrow cellularity, as well as elevation of blood concentration of the hemoragulatory cytokines IL-3 and IL-6.

Animals↗

[Immunotherapy in aplastic anaemia as a cause of reactivation of hepatitis B virus-immunologic aspects].

We present history of 16-year-old boy, HBsAg carrier, treated with interferon alpha at the age of 6 because of hepatitis B (HBeAg/antyHBe seroconversion). In August 2002--admitted to Department of Pediatric Oncology due to pancytopenia--diagnosis of severe aplastic anaemia was made (bone marrow cellularity--10%). We found no relative donor for hematopoietic cells transplantation and started immunosuppresive therapy (ATG, G-CSF, methyloprednisolon, cyclosporin). Haematologic parameters were improving. At day +60 he was admitted to our Department due to the increase in aminotransferases and cyclosporin activity. He was treated with cefuroxim, acyclovir and drugs improving liver cell function, cyclosporin was stopped. Presence of HBV DNA in serum confirmed HBV reactivation--a boy received lamivudine and cyclosporin again (as a maintenance therapy of aplastic anaemia). Aminotransferase activity and haematological parameters returned to normal. This case indicates the possibility of HBV reactivation in the course of immunosuppressive therapy (e.g. after antithymocytic globulin and cyclosporin) for aplastic anaemia.

Anemia, Aplastic↗

Combined therapy with recombinant granulocyte colony-stimulating factor and erythropoietin decreases hematologic toxicity from zidovudine.

Twenty-two patients with acquired immunodeficiency syndrome (AIDS) or severe AIDS-related complex and multilineage hematopoietic defects were treated with recombinant granulocyte colony-stimulating factor (G-CSF) and erythropoietin (EPO) in a phase I/II trial. All patients were neutropenic and anemic after withdrawal of all bone marrow-suppressive drugs. Daily, G-CSF was subcutaneously self-administered until an absolute neutrophil count (ANC) greater than 6,000/microL was achieved and maintained for 2 weeks. Subcutaneous EPO was added to the regimen and the dose increased until an increase of 15 g/L of hemoglobin was observed. Groups of patients were administered increasing doses of zidovudine to determine their tolerance. G-CSF and EPO therapy was continued with dose modification to maintain an ANC greater than 1,500/microL and hemoglobin greater than 100 g/L. The dose of zidovudine was not altered. All 22 patients responded to G-CSF with a mean 10-fold increase in neutrophils occurring in less than 2 weeks. Significant increases in CD4 and CD8 cell number, lymphocyte proliferative response, and bone marrow cellularity were seen. EPO therapy increased hemoglobin in all 20 evaluable patients within 8 weeks. Sixteen patients received 1,000 mg and four patients received 1,500 mg of zidovudine per day. The reinstitution of zidovudine resulted in a decline in reticulocytes and hemoglobin and the reappearance of transfusion requirements in eight of the 20 patients, six of whom had the study medications stopped. No patient had the study medications stopped because of neutropenia or thrombocytopenia. Toxicities were mild and did not require dose modifications. Limiting dilution plasma and lymphocyte co-cultures for HIV as well as serum p24 antigen levels did not change significantly during G-CSF or combined G-CSF and EPO therapy. HIV p24 antigen decreased significantly with zidovudine therapy. Opportunistic infections occurred in 14 patients but were successfully treated with myelosuppressive antimicrobial agents, including ganciclovir, without the development of neutropenia. These results suggest that combined therapy with G-CSF and EPO may improve the neutropenia and anemia of AIDS. Combined therapy may allow the resumption of full-dose zidovudine in most patients intolerant of the hematologic effects of zidovudine without apparent alteration of HIV expression or the efficacy of zidovudine.

Acquired Immunodeficiency Syndrome↗

A clinico-haematologic profile of paroxysmal nocturnal haemoglobinuria.

Clinico-haematological parameters in sixteen patients of paroxysmal nocturnal haemoglobinuria (PNH) are presented. Their modes of presentation included recurrent episodes of cola-coloured urine (6/16), refractory anaemia (9/16) and predominant thrombotic manifestations (1/16). Laboratory investigations revealed the presence of anaemia (16/16), reticulocytosis (14/16), thrombocytopenia (11/16), leucopenia (5/16) and cellular bone marrow (14/16). Two patients had hypoplastic bone marrow initially but subsequently developed PNH. The patients were treated with haematinics, prednisolone (16/16) and oxymethalone (2). Prednisone was effective in suppressing haemolytic episodes. Oxymethalone given to the 2 patients with hypoplastic bone marrow resulted in amelioration of anaemia in one but no effect in the other patient.

Adolescent↗

[The antiradiation properties of betamide under conditions of sublethal and lethal gamma irradiation].

Bone marrow cellularity in the femur, mass and cellularity of the spleen and small intestine, and nucleic acid concentration in the leukocyte mass of blood were investigated after the intraperitoneal administration of betamide (500 mg/kg) 15 min before gamma irradiation of mice with doses of 4, 7 and 9 Gy. The number of myelokaryocytes and splenocytes in the protected animals was shown to exceed considerably that in the controls on days 3 and 9 after irradiation with the three doses. With betamide injected on day 9 following irradiation the number of nucleated cells of the small intestine was larger and the nucleic acid concentration in leukocytes higher than the same indices in the irradiated control.

Acute Disease↗

[Reticulocytopenia and neutropenia in 3 patients with idiopathic autoimmune hemolytic anemia].

Retyculocytopenia and neutropenia or both abnormalities are very infrequent findings during the evolution of patients with acquired autoimmune hemolytic anemia (AIHA). In this paper we describe the clinical cases of three patients with AIHA in whom six different periods of reticulocytopenia were identified; the first two patients also had neutropenia. At the moment of the diagnosis of the cytopenias, the patients did not have a systemic disease, a viral infection or received immunosuppression able to produce them. In every patient the bone marrow cellularity was increased mostly at the expense of normal and macroerythroblasts, containing significant amounts of the other hematopoietic cells. After the diagnosis of AIHA, the patients received supplementary treatment with folic acid which did not produce a remission. The remissions were related to steroids: the neutrophil counts increased importantly one to ten days after starting the steroid administration, whereas reticulocytes reappeared more slowly from 7 to 30 days post-initiation. In patients with AIHA the occurrence of reticulocytopenia and neutropenia have been related to several causes. The favorable responses to steroids in our cases suggests a relationship of steroid with the immunological changes in AHA. It should be pointed out that it is necessary to prolong the followup as done in our three cases. Although these cytopenias may be independent from the hemolytic anemia, we feel our cases suggest that they could be manifestations of a pathologic state not yet characterized.

Adult↗

[The granulocyte-macrophage colony stimulating factor and the radiation protective effect of yeast mannan].

The effect of mannan polysaccharide on the haemopoiesis recovery in irradiated mice has been investigated. Mannan has been shown to exert both the protective and the stimulatory effect: it accelerates restoration of femur bone marrow cellularity and nucleate cell number in the peripheral blood and causes a larger initial yield and subsequent more rapid postirradiation dynamics of pluripotent haemopoietic stem cells and precursor cells of granulocytes and macrophages.

Animals↗

[Effect of the administration of rhGM-CSF in a patient with marrow aplasia resistant to immunosuppressive treatment].

The treatment of patients with refractory bone marrow aplasia in whom bone marrow transplant cannot be performed is unsatisfactory. Infections and haemorrhages are the most frequent cause of death in such patients. Human recombinant proteins from haemopoietic growth factors provide new therapeutic possibilities. The clinical and biologic course of one such patient treated with rhGM-CSF is reported here. The patient had severe bone marrow aplasia refractory to immunosuppressive treatment, and an improvement of leucocyte, neutrophil and eosinophil counts, along with the healing of an infection only partially controlled with antibiotics, followed the administration of rhGM-CSF. However, such peripheral blood improvement was not accompanied by any increase of bone marrow cellularity, as measured by conventional histopathologic methods, and the patient died due to ictero-ascitic evolution of post-transfusion chronic liver disease.

Anemia, Aplastic↗

Tumor inhibition and hematological improvements by dopamine analog 3,4-dihydroxybenzylamine in mice bearing transplantable carcinoma.

The cancer chemotherapeutic efficacy of 3,4-dihydroxybenzylamine (DHBA), a dopamine analog with reduced neurotoxic effects, was evaluated in strain A mice bearing transplantable Ehrlich's ascites carcinoma. The analog was administered intraperitoneally on day 1 post-transplantation at dose schedules of 50, 100 and 200 mg/kg/day for 7 consecutive days. The results demonstrated a significant inhibition of tumor growth and prolongation of the survival time of EAC tumor bearing mice following DHBA treatment. Diminished activity of the growth-related respiratory enzyme succinate dehydrogenase along with the stimulated activity of the lysosomal enzyme beta-glucuronidase in the DHBA-treated tumor cells indicated inhibition of tumor growth as well as active lysis of the tumor cells. Tumor inhibition was accompanied by marked improvements in hemoglobin concentration. RBC count and bone marrow cellularity. The results demonstrated that DHBA did not adversely affect hematological profile of the host while it inhibited the growth of Ehrlich's ascites carcinoma.

Animals↗

Clinical aspects of the myelodysplastic syndromes (MDS) with special reference to refractory anemia with excess of blasts (RAEB).

Clinical features, prognosis and factors influencing survival, as well as long-term evolution of the disease were analyzed in 130 patients with myelodysplastic syndromes (MDS) with particular reference to the refractory anemia with excess of blasts (RAEB). Survival of patients with 3 FAB subtypes, RAEB, RAEB in transformation (RAEB-T) and chronic myelomonocytic leukemia (CMMoL) showing excess blasts was uniformly poor relative to primary acquired refractory anemia (PARA) and primary acquired sideroblastic anemia (PASA). The degree of cytopenias, karyotypic abnormalities, bone marrow cellularity, transition to acute leukemia were not reliable prognostic parameters for discrimination of RAEB with poor or good prognosis. Disease transition was frequently observed in our MDS patient population, at an overall incidence of 37.7%. Transition of PARA to RAEB occurred after a prolonged course in some patients.

Adolescent↗

Development of neomycin-resistant WEHI-3B D+ murine cells as an in vivo model of acute nonlymphocytic leukemia.

pSV2 neomycin DNA was electroporated into exponentially growing WEHI-3B D+ cells, and clones containing integrated pSV2 neomycin DNA were selected by treatment with the antibiotic Geneticin. Southern analysis after Eco RI or Bam HI and Hind III digestion demonstrated that two clones, Y1 and Y2, stably incorporated a single copy of intact pSV2 neomycin DNA into different sites. Exposure of parental WEHI-3B D+ cells to retinoic acid, aclacinomycin A, or adriamycin resulted in their differentiation to mature granulocytic cells. Clone Y1 had growth kinetics and numbers of differentiated cells comparable to those of the parental line when exposed to these differentiation-inducing agents. Furthermore, this clone was leukemogenic in BALB/c mice. The disease presented as a moderate anemia, a peripheral blood granulocytosis, a shift in the differential to immature granulocytic forms, and a thrombocytopenia. Although there was no change in bone marrow cellularity, in situ hybridization to identify the presence of the neomycin resistance gene mRNA indicated infiltration of leukemia cells (up to 30%) into this tissue compartment. The observed hematological parameters were indicative of a late stage of disease resembling human acute nonlymphocytic leukemia. Clone Y1, therefore, would appear to be an in vivo model of acute nonlymphocytic leukemia that may be useful for the development of therapeutic strategies to more successfully treat these diseases. Because we have demonstrated that this line is capable of differentiation in vitro and can be stably carried in vivo, it would also be useful for the identification of therapeutic agents capable of initiating the differentiation of leukemia cells in situ.

Animals↗

[Treatment of acute myeloblastic leukemia in elderly patients with low-dose cytosine arabinoside].

Forty-eight patients, aged from 65 to 88 years, presenting with de novo acute myelogenous leukemia were treated with a low-dose cytarabine regimen (10 mg/sq.m subcutaneously 12-hourly for 15 to 28 days). Twenty-four complete remissions and 7 partial remissions were obtained. The complete remission rate correlated with low initial bone marrow cellularity (p less than 0.05). Bleeding occurred in 28 patients and fever was noted, also in 28 patients. Four patients died of infection during induction treatment. Fourteen patients were treated as out-patients, but regular medical supervision was necessary. The median duration of complete remission was 8 months. The median survival for all patients was 15 months. It is concluded that low-dose cytarabine is an alternative to intensive chemotherapy in elderly patients with acute myelogenous leukemia.

Aged↗

[Modification of the radiation injury of hematopoiesis in rats using the gaseous hypoxic mixture GHM-10].

In experiments on Wistar rats it was shown that gas hypoxic mixture containing O2 (10%) and N2 (90%) had a radioprotective action with regard to the survival rate for 30 days and to the haemopoietic system status. The application of gas hypoxic mixture reduced the postirradiation cytopenia in the blood and lowered the degree of the bone marrow depletion by the 3d day following irradiation; DMF was 1.25 as determined by total bone marrow cellularity.

Animals↗

[Typhoid fever presenting as histiocytic medullary reticulosis: a case report].

Because of a pancytopenia, moderately cellular bone marrow with hypoplastic erythropoiesis but with active granulo- and thrombopoiesis and a conspicuous increase in histiocytic cells, a patient was provisionally diagnosed as having histiocytic medullary reticulosis. However, Salmonella typhi was cultured from blood, urine and stool specimens. After 3 weeks the Widal reaction showed a titre of 1/320 for the H-antigen and 1/1,280 for the O-antigen. The patient was treated with chloramphenicol for 10 days and the fever, enlarged spleen and enlarged lymph nodes returned to normal.

Diagnosis, Differential↗

Late effects of single and repeated sublethal gamma radiations on haemopoietic stem cells in mice.

The effects of single (1 X 5 Gy) and repeated (4 X 5 Gy) gamma-ray doses, separated by 21 days, on femoral CFU-S numbers in mice during the 12 months after irradiation were compared. Nucleated cell and CFU-S numbers were recovered 21 days after whole-body irradiation with 5 Gy. Marrow regeneration was not sufficient after the second irradiation, and nucleated cell and CFU-S numbers reached 50% of the level of the control 21 days after the second dose. The decrease in CFU-S numbers was more marked after the third and fourth doses, reaching 35% of the control. While CFU-S numbers were recovered by the 21st day after a single dose of 5 Gy, the level of the control group was reached 60 days after the last dose of repeated (4 X 5 Gy) gamma irradiation. A decrease in femoral CFU-S numbers occurred in both irradiated groups 6 months after the last dose, the decrease having been more marked in the group exposed to repeated irradiations. The decrease was more pronounced 12 months after irradiation although bone marrow cellularity was at the level of the unirradiated group. Femoral CFU-S numbers were lower in unirradiated 480-day-old mice than in those at 120 days of age.

Age Factors↗

Myelodysplastic syndrome in two dogs.

Two cases of myelodysplastic syndrome in the dog are described. Both cases were characterized by hepatomegaly, cytopenias, macrocytosis, cellular bone marrow, and dysplastic changes in all hematopoietic cell lines. Serum vitamin B12 and folic acid concentrations were within reference ranges in one dog, but vitamin B12 was slightly decreased in the other. Vitamin B12 therapy did not result in amelioration of the hematologic disorder. The duration of illness was approximately 5 months. Necropsy of one dog revealed an acute undifferentiated leukemia.

Anemia↗