Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

From 1967 to 1972, 70 patients with aplastic anemia were observed and followed up to death or at least two years. 3 cases of pure red cell anemia, and 2 cases of amegakaryocytic thrombocytopenia are included. Detailed investigation of drugs taken within 6 months before onset of the disease revealed chloramphenicol in 20, butazones in 11 cases. Acute viral hepatitis preceded the hemopoietic failure in 2 patients. In addition to various combinations of anemia, granulocytopenia and thrombocytopenia, monocytes were diminished in 35 and lymphocytes in 12 cases. Acid serum or sucrose tests were consistently negative. The patients were treated by short-term prednisone, long-term androgens and red cell and platelet substitution as needed. 2 years after onset of the disease, 33 per cent were in partial or complete remission, 30 per cent survived without remission, and 35 per cent had decreased. Correlation of various parameters with remission and survival showed the presence of a subgroup at risque, comprising patients with low marrow cellularity and clinically relevant diminution of all three cell lines at the time of diagnosis. Absolute lymphopenia and increase of plasma cells in the bone marrow were of poor prognostic significance. In this subgroup two years after the onset of the disease only 32 percent survivors and 16 per cent remissions were recorded. There was no conclusive evidence for the therapeutic value of prednisone or androgens in our series. The present situation in severe aplastic anemia requires more effective forms of treatment and justifies experimental therapies like bone marrow transplantation.
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PMID:[Course and prognosis of panmyelopathy and isolated aplastic anemia. Retrospective study in 70 patients]. 112 32

In the development of clinical strategies to manage radiation accident casualties, the medical doctor in charge should be encouraged to use a "decision tree" to establish by a "sequential diagnosis procedure". This should be done within the first few days after exposure to determine whether or not a spontaneous recovery of hemopoietic function can be expected. With the assistance of a computer simulation model it appears possible to relate certain granulocyte response patterns to the extend and quality of damage caused in the hematopoietic stem cell pool. The determination of this damage is of great importance because it quantifies the strain inflicted upon the hemopoietic system by radiation exposure. It must be remembered that some stem cells are intact or are able to repair the damage completely. These stem cells serve as the ultimate source of hemopoietic recovery. The other stem cells that are left with the restricted hematopoietic potential are the source for the so called abortive recovery. On this basis it must be recognized that the day-to-day detailed analysis of documentation of blood cell changes for the first 5-10 days after exposure is of critical importance in order to be able to answer the question whether a spontaneous hemopoietic recovery can be expected or not. If the stem cell pool is sufficiently damaged (less than 6-8 in 10,000 stem cells) then one can expect a particular constellation of blood cells around day 5-7 characterized by severe granulocytopenia, severe lymphopenia and beginning thrombocytopenia. This blood cell response pattern is indicative of an irreversible stem cell damage. In this case, a transplantation of stem cells may well be life saving if done using the criteria developed for the treatment of severe aplastic anemia by bone marrow transplantation including an appropriate conditioning regimen for immune suppression.
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PMID:Early indicators of response to accidental radiation exposure and the relevance for clinical management strategies. 195 14

Corticosteroids and anti-thymocyte globulin (ATG) have been extensively used in the treatment of autoimmune diseases, aplastic anemia and organ graft rejection; nonetheless, the precise mechanisms of action of these agents are unknown. Studies of their long term immunoregulatory effects, particularly in humans, have been limited. We examined the long term effects of therapy with ATG given for 2-4 weeks and prednisone for 2 months in 4 patients with newly diagnosed insulin dependent diabetes (IDD). Three matched newly-diagnosed untreated IDD patients and 17 healthy volunteers served as controls. No differences in total lymphocyte count, percentage of B cells, percentage of total T cells (CD3), helper-inducer T cells (CD4) or cytotoxic-suppressor cells (CD8), lymphocyte blastogenesis assays, or pokeweed mitogen-induced IgG secretion in T & B cell co-cultures were detected before therapy. A transient lymphopenia following ATG administration was the only immunological defect found in the first month of therapy. At 2 months, however, patients treated with ATG and prednisone had diminished immunoregulatory T cell function demonstrated by production of only 28 +/- 3% IgG expected in T & B co-culture, compared to 205 +/- 35% for untreated IDD patients and 107 +/- 13% for normals (p less than 0.01). This diminished IgG production resulted from excessive suppressor function, since co-cultures of T cells from treated patients with T and B cells from normal volunteers suppressed the latter's IgG production by 76 +/- 9%. This enhanced suppressor activity persisted for 3-6 months following therapy. Other immunological functions were not statistically different from those present at the inception of the study. Thus, treatment with corticosteroids and ATG produces long-term enhanced suppressor activity, a finding which suggests that treatment with combination ATG and Prednisone is a rational form of immunomodulation in conditions associated with decreased suppressor function.
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PMID:Long-term immunoregulatory effects of therapy with corticosteroids and anti-thymocyte globulin. 269 66

Thirty-five patients with severe aplastic anaemia (SAA) were extensively evaluated 0.3-12.4 years (median 3.8) after anti-thymocyte globulin (ATG) treatment. All but one were transfusion independent. Most patients revealed a normal Hb level and a granulocyte count over 1.5 x 10(9)/l but were still thrombocytopenic due to decreased platelet production. Lymphocytopenia and/or monocytopenia was found in about 30%. Two patients had a monocytosis. Although there was a great range in degree of recovery at various time intervals after ATG, patients tested more than 4 years after ATG tended to have higher cell counts. Lymphocyte counts correlated with the interval between ATG and evaluation, and with haematopoietic recovery. Qualitative abnormalities were found in all cell lines. Most patients showed a homogeneous macrocytic RBC population, and almost 50% a positive sucrose lysis test; only three patients showed evidence of haemolysis and only two of these showed a positive Ham test. Mean platelet volumes were reduced out of proportion to their number. Platelet function, determined by bleeding time and aggregometry, was impaired in over 30%. The granulocytic series showed a shift to the left in about 30%. Hypersegmentation and pseudo Pelger-Huet anomaly were seen in some patients. Lymphocyte subset distribution in blood and bone marrow was within the normal range but absolute blood levels of CD4 cells in particular were slightly decreased, and tended to increase gradually with time after ATG. IgG and IgA levels were significantly decreased. In only one patient cytogenetic analysis of unstimulated bone marrow cells revealed an abnormal karyotype, but in eight of eight patients an increased sensitivity of lymphocytes to X-rays was found. These data suggest impairment at the level of the very early haematopoietic progenitor cell in all patients up to 10 years after ATG. Since similar findings have been reported in clonal (pre-)malignant disease, SAA, improved after ATG treatment, might be prone to clonal (malignant) evolution.
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PMID:Haematopoietic and immunologic abnormalities in severe aplastic anaemia patients treated with anti-thymocyte globulin. 278 88

We describe veno-occlusive disease of the liver associated with humoral and cellular immune defects in two siblings. Another child, with aplastic anemia, died before the age of 1 year. No consanguinity was found in the family. Both infants had lymphopenia and hypogammaglobulinemia; the surviving infant has defective in vitro immunoglobulin production after stimulation of lymphocytes with pokeweed mitogen, increased proportions of OKT8 positive cells, defective proliferative responses to phytomitogens, and decreased help for immunoglobulin production. A therapeutic trial with cimetidine, an H2 receptor antagonist, has not changed the immunologic status of the surviving child.
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PMID:Defective humoral and cellular immune functions associated with veno-occlusive disease of the liver. 355 2

Lymphocyte phenotype, bone marrow cellularity, in vitro marrow growth potential, and treatment responses were examined in 22 patients with acquired aplastic anemia who were given anti-thymocyte globulin. Eleven of 22 patients (50 percent) had a significant hematologic response within three months of therapy, confirming the effectiveness of this therapy. Pretreatment fetal hemoglobin concentration, age, sex, severity of pancytopenia, degree of maximal lymphopenia, and total hemolytic complement consumption did not affect response. Patients with severe disease who were treated within 16 weeks after diagnosis had a higher response rate (55 percent) than those treated after 16 weeks (20 percent). In patients with severe disease, a higher pretherapy bone marrow cellularity (p less than 0.001) and presence of granulocyte-macrophage colony growth correlated with response. The actuarial survival of patients with response in the group with severe disease was 100 percent at 12 months as compared with 33 percent in patients without response. Following anti-thymocyte globulin therapy, a reduced number of blood lymphocyte T subpopulations was seen in all patients. At three months after therapy, the patients with response who had severe disease had increased T8-positive cells (+56 percent versus -4 percent for patients without response) and la-positive cells (+32 percent versus -62 percent).
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PMID:Predictive factors for response to anti-thymocyte globulin in acquired aplastic anemia. 387 46

Colony forming unit (CFU) assays were developed for feline granulocyte-macrophage (CFUGM), early erythroid (day 2 CFUE), and late erythroid (day 7 CFUE) colonies in methylcellulose medium. Feline CFUGM and both day 2 and day 7 CFUE were enhanced by feline macrophage conditioned medium and late CFUE often were intimately associated with macrophages. Kittens were inoculated with the Kawakami-Theilen (KT) strain of feline leukemia virus (FeLV) and sequential changes in marrow CFU determined. Erythroid aplasia, characterized by progressive non-regenerative anemia, lymphopenia, and a profound decrease in early and late CFUE but not CFUGM was induced by 3 to 5 weeks after FeLV-KT inoculation. The susceptibility of kittens to FeVL-induced erythroid aplasia was strongly age-related; neonatal kittens were most sensitive and substantial natural resistance developed by 4 weeks of age. The results demonstrate that FeLV-KT infection induced a rapid and selective suppression of erythroid progenitor cells and represents a suitable model of experimentally-induced acquired erythroid aplasia.
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PMID:Feline leukemia virus-induced erythroid aplasia: in vitro hemopoietic culture studies. 627

In vitro and in vivo immunologic parameters were determined in 26 patients treated continuously with cyclosporine to prevent graft-versus-host-disease (GVHD) after allogeneic bone marrow transplantation (BMT) for acute and chronic leukemia and for aplastic anemia. A group of 18 patients was tested 6 months after BMT and another group of 10 patients was tested after one year. At 6 months after BMT, 94% of the patients had normal serum IgG and IgM levels, whereas at one year 29% of them had low IgA levels. The proportion of patients with normal lymphocyte responses in vitro at 6 months after BMT was 69% and 76% for the responses to concanavalin A and to soluble antigens; 75% and 53% for the responses to allogeneic cells and pokeweed mitogen, respectively; and 89% for the response to phytohemagglutinin. All but one were able to generate suppressor cells upon con A stimulation. At one year after the graft, only one patient had demonstrable multiple abnormalities in in vitro tests. Skin test reactivity at one year was comparable to pre-graft reactivity. After BMT a lymphopenia persisted for 6 months. The rate of infectious complications was high during the first 3 months after BMT, and it diminished progressively as immune functions returned to normal. Infection was the cause of death in two cases (one disseminated cytomegalovirus infection and one septicemia). GHVD occurred in 12 patients; in nine of them the disease was transient and mild, only 1 patient developed severe chronic GVHD. Acute GVHD did not influence the tempo of immunologic reconstitution. In comparison to other studies, it seems that cyclosporine does not delay immune restoration, or increase morbidity from infection, while preventing GVHD and its complications efficiently.
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PMID:Immunologic reactivity in marrow graft recipients receiving cyclosporine to prevent graft-versus-host disease. 634 34

2-Chlorodeoxyadenosine (cladribine, Leustatin) is being used extensively in the treatment of hematologic malignancies, but relatively little is known regarding its toxicity to the normal marrow. Long-term serial hematologic observations have been made on 29 patients with multiple sclerosis undergoing experimental therapy with monthly courses of cladribine, each of which consisted of 0.087-0.1 mg/kg per day for 7 days. The characteristic hematologic responses of the patients consisted of acute transient monocytopenia, prolonged, profound lymphopenia especially of CD4-positive cells, and modest lowering of the granulocyte count and hemoglobin with development of long-lasting macrocytosis. Two patients developed severe aplastic anemia, requiring transfusion both of red cells and platelets. One of these had previously received extensive therapy with chlorambucil, while the other had received carbamazepine (Tegretol) and was ingesting phenytoin (Dilantin) at the time of cladribine therapy. Both patients recovered after several months of marrow suppression.
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PMID:Marrow suppression produced by repeated doses of cladribine. 817 30

The toxic effects of environmental factors at work places on the hematopoietic and immune systems are of basic importance due to the time of exposure, lasting on average 8 hours daily during one week. Porphyrinurias and porphyrias have been observed after exposure to hexachlorobenzene, chlorinated dibenzodioxins, polychlorinated biphenyls, polybrominated biphenyls, vinyl chloride and lead. Aplastic anemia may occur after exposure to benzene, pesticides, arsenic, cadmium and copper compounds. Megaloblastic anemia has been noted in subjects exposed to arsenic, chlordane, benzene and nitrous oxide. Methemoglobinemia is induced by aromatic nitro and amino compounds. Hemolytic reactions caused by arsenic, methyl chloride, naphthalene, lead, cadmium and mercury compounds represent a separate problem. Immunodeficiencies resulting in decreased antitumor and antiinfectious immunity have been reported in subjects exposed to asbestos, ozone, dimethylsulphoxide, vinilidene chloride, and benzene homologues. Lymphocytopenia may be induced by manganese, lead, toluene and industrial noise. Neutropenia was marked after exposure to carbon disulphide, arsenic compounds, benzene and electromagnetic fields. Only a few reports concern the lymphocyte T3, T4 and T8 subpopulations. Electromagnetic fields (microwaves) cause an imbalance of that subpopulation, consisting of a decrease in the T8 cell count. The neutrophil enzymes, such as myeloperoxidase and alkaline phosphatase, decrease in their activity after exposure to polychlorinated biphenyls, carbon disulphide, chlorobenzene and DDT. A majority of agents cited include genotoxic effects reflected in chromosome aberrations and increased sister chromatid exchange and abnormal unscheduled DNA synthesis. Leukemia or lymphoma risk is increased after exposure to pesticides, electromagnetic fields, benzene and irradiation.
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PMID:Immunotoxic and hematotoxic effects of occupational exposures. 817 62


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