Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Felty's syndrome, consisting of rheumatoid arthritis, leukopenia, and splenomegaly, has been recognized as a distinct clinical entity for more than 60 years. Clinical and laboratory manifestations of the condition are reviewed. The major sources of morbidity and mortality remain recurrent local and systemic infections. Immunogenetic analysis shows a strong association with HLA-DR4, in addition to DQ beta 3b and C4B null allele. Potential mechanisms of neutropenia are contrasted, including impaired granulopoiesis and neutrophil-immune complex interactions. Lithium carbonate and splenectomy may have a role in the treatment of fulminant disease. Maintenance therapy should be directed at control of the underlying inflammatory arthropathy. A syndrome of proliferation of large granular lymphocytes and neutropenia, associated with rheumatoid arthritis in 23% to 39% of cases, has been described recently. Cases of "pseudo-Felty's" syndrome are often confused with traditional Felty's syndrome, which has twice the prevalence. The clinical and laboratory distinctions between these two conditions are elaborated.
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PMID:Felty's and pseudo-Felty's syndromes. 178 50

We describe a case of Felty's syndrome with persistent severe neutropenia below 200 granulocytes/mm3, splenomegaly and repeated infections. The patient did not respond to treatment with intramuscular gold salts and lithium carbonate. After 2 months of oral methotrexate administration, 7.5 mg weekly, clinical improvement was notable: she remained afebrile, neutropenia disappeared and splenomegaly regressed. This clinical and laboratory improvement persisted 5 months later. Moreover, accidental discontinuance of the drug and later readministration supported the evidence that the improvement was due to methotrexate.
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PMID:Felty's syndrome: response to low dose oral methotrexate. 185 26

Twelve adult patients with acute lymphoblastic leukemia (ALL) received lithium carbonate, 300 mg, three times a day during induction treatment. They were compared to 12 similar patients consecutively treated with the same induction regimen; patients and controls were comparable for age, degree and presence of splenomegaly, hemoglobin level, blast cell count, polymorphonuclear (PMN) cell count and platelet count at diagnosis. All patients developed a severe neutropenia. PMN count at nadir was slightly higher in the lithium group, but not at a level of statistical significance (p = 0.100). The median number of days with PMN less than 1 x 10(9)/liter was 4 in the lithium group and 14.5 in the non-lithium group (p = 0.014), while the median number of days with PMN less than 0.5 x 10(9)/liter was 0 and 2 days, respectively (p = 0.004). Duration of thrombocytopenia was similar in the 2 groups and so was the remission rate; 2 infective episodes occurred, one in the lithium group and one in the controls.
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PMID:Lithium and granulocytopenia during induction treatment of adult acute lymphoblastic leukemia. 696 May 90

Lithium salts have been demonstrated to induce the production of hematopoietic cells following administration in vivo and to minimize the reduction of these cells following treatment with either radiation, chemotherapeutic or antiviral drugs. We have previously demonstrated that lithium, when administered in vivo to immunodeficient mice infected with LP-BM5 MuLV (MAIDS) significantly reduced the development of lymphadenopathy, splenomegaly, and the lymphoma associated with late-stage immunodeficiency disease in this model, and increased the survival of these animals compared to virus-infected controls not receiving lithium. We report here the results of in vivo studies in the MAIDS model that determined the effect of lithium on peripheral blood indices and the number of myeloid (CFU-GM), erythroid (BFU-E) and megakaryocyte (CFU-Meg) hematopoietic progenitors from bone marrow and spleen harvested from immunodeficient mice receiving lithium carbonate (1 mM) placed in their drinking water compared to virus-infected controls not receiving lithium. Time-points evaluated were at weeks 1, 5, 9, 13, 17, and 21 postviral infection. Virus-control mice not receiving lithium demonstrated all the signs that are characteristic of MAIDS, i.e., splenomegaly, lymphadenopathy, hypergammaglobulinemia, reduced hematopoiesis, and death. Infected mice receiving lithium demonstrated diminished presence of splenomegaly, lymphadenopathy, hypergammaglobulinemia, no suppression of hematopoiesis nor mortality. Enhanced hematopoiesis was demonstrated by neutrophilia, lymphocytosis, thrombocytosis, and erythrocytosis that was evident by increased myeloid, erythroid, and megakaryocyte progenitor cells cultured from bone marrow and spleen. These studies further demonstrate that lithium influences the disease process in the MAIDS model and restricts the development of hematopoietic suppression that develops in this retroviral animal model of immunodeficiency.
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PMID:Effect of lithium in immunodeficiency: improved blood cell formation in mice with decreased hematopoiesis as the result of LP-BM5 MuLV infection. 760 15

The NBC1 Na+/HCO3- cotransporter is expressed in many tissues, including kidney and intestinal epithelia. NBC1 mutations cause proximal renal tubular acidosis in humans, consistent with its role in HCO3- absorption in the kidney. In intestinal and colonic epithelia, NBC1 localizes to basolateral membranes and is thought to function in anion secretion. To test the hypothesis that NBC1 plays a role in transepithelial HCO3- secretion in the intestinal tract, null mutant (NBC1-/-) mice were prepared by targeted disruption of its gene (Slc4a4). NBC1-/- mice exhibited severe metabolic acidosis, growth retardation, reduced plasma Na+, hyperal-dosteronism, splenomegaly, abnormal dentition, intestinal obstructions, and death before weaning. Intracellular pH (pH(i)) was not altered in cAMP-stimulated epithelial cells of NBC1-/- cecum, but pH(i) regulation during sodium removal and readdition was impaired. Bioelectric measurements of NBC1-/- colons revealed increased amiloride-sensitive Na+ absorption. In Ringer solution containing both Cl- and HCO3-, the magnitude of cAMP-stimulated anion secretion was normal in NBC1-/- distal colon but increased in proximal colon, with the increase largely supported by enhanced activity of the basolateral NKCC1 Na+-K+-2Cl- cotransporter. Anion substitution studies in which carbonic anhydrase was inhibited and transepithelial anion conductance was limited to HCO3- revealed a sharp decrease in both cAMP-stimulated HCO3- secretion and SITS-sensitive current in NBC1-/- proximal colon. These results are consistent with the known function of NBC1 in HCO3- absorption in the kidney and demonstrate that NBC1 activity is a component of the basolateral mechanisms for HCO3- uptake during cAMP-stimulated anion secretion in the proximal colon.
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PMID:Colonic anion secretory defects and metabolic acidosis in mice lacking the NBC1 Na+/HCO3- cotransporter. 1719 75