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)

Ten patients with progressive follicular lymphomas (seven with follicular mixed lymphomas, three with follicular, small cleaved cell lymphomas) with clinical indications for systemic therapy received parenteral suramin. Each had failed from one to six prior chemotherapeutic regimens and three had in addition received prior radiation therapy. All had measurable disease and nine of the ten had documented bone marrow involvement at the start of therapy. Suramin was administered at an initial infusion rate of 350 mg/m2/day, which was then modified on the basis of subsequent weekly plasma suramin concentrations in order to reach a final plasma concentrations of 250-350 micrograms/ml. Treatment cycles were repeated at eight week intervals. Nine of ten patients are evaluable for response. Five of nine evaluable patients achieved a partial remission as defined by a greater than 50% decrease in the sum of the product of all measurable lesions. Sites of response include: Peripheral (five patients) and central (four patients) adenopathy, disappearance of biopsy-proven skin involvement (one patient), malignant pleural effusions (one patient) and shrinkage of an enlarged spleen (two patients). Disappearance of B symptoms occurred in the one responder with these symptoms. Response duration varied from 3 to 9 months (mean 5.6 months) with time to subsequent systemic therapy varying from 5 to 12 months (mean 8 months). Drug related toxicity included the development of polyradiculopathy (one case), liver function abnormalities (three cases), thrombocytopenia (five cases), vortex keratopathy (two cases) and bacterial infection (two cases). We conclude that suramin has significant activity against follicular lymphomas refractory to standard chemotherapy and that its precise role in the treatment of lymphoproliferative neoplasms in general warrants further investigation.
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PMID:A pilot study of suramin in the treatment of progressive refractory follicular lymphomas. 149 80

Thirty-two patients with the Felty syndrome, defined by the presence of rheumatoid arthritis, splenomegaly, and neutropenia, have been studied in comparison with 32 patients with rheumatoid arthritis matched for age, sex, and disease duration, and 9 patients with rheumatoid arthritis and idiopathic neutropenia. Patients with the Felty syndrome had severe destructive arthritis, which progressed during follow-up despite little evidence of objective synovitis, and a higher frequency of extra-articular manifestations, including vasculitis. Bacterial infection tended to occur in patients with the lowest neutrophil count but continued to occur in some despite normalization of the WBC. Prognosis was poor and 8 deaths occurred, predominantly from sepsis. Serologic features were prominent. High titers of IgG rheumatoid factor and circulating immune complexes characterized patients with persistent neutropenia. A family history of rheumatoid arthritis was more common in patients with the Felty syndrome. The association with HLA DR4 was very strong; in addition there was an increased frequency of the DQw3 variant, 3b, suggesting that HLA Class II genes in linkage with DR4 may contribute to disease expression.
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PMID:The Felty syndrome: a case-matched study of clinical manifestations and outcome, serologic features, and immunogenetic associations. 196 4

Two patients admitted to the hospital because of severe bacterial infection were diagnosed as having visceral leishmaniasis. The types of bacterial infection were perianal abscess and pneumonia; Escherichia coli and Streptococcus pneumoniae were isolated from exudates and blood cultures, respectively. A third patient admitted because of acute necrotizing infection of the pharynx and visceral leishmaniasis is also discussed. Cultures from this patient failed to yield pathogens. Anemia, leukopenia, or thrombocytopenia was present in all patients, and bone marrow aspirate revealed the presence of Leishmania in macrophages. We conclude that in areas where leishmaniasis is endemic, early bone marrow aspirate should, in most instances, be performed in patients with bacterial infection associated with anemia, leukopenia, or thrombocytopenia if hepatomegaly and/or splenomegaly is present.
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PMID:Bacterial infection as a presenting manifestation of visceral leishmaniasis. 219 55

Clinical evidence suggests that individuals with chronic iron overload may be at increased risk of bacterial infection. We studied this question by using a unique model in which mice homozygous for a deletion in the gene encoding for the beta-major globin develop moderate anemia, splenomegaly, and tissue iron overload, a syndrome similar to beta-thalassemia in humans. Mice heterozygous for the gene deletion were phenotypically normal. Homozygous mice were significantly more susceptible to infection with Listeria monocytogenes than were heterozygous mice (P less than 0.01). This increased susceptibility was associated with a greater number of organisms in the liver and spleen than was found in heterozygous mice (P less than 0.05). However, histologic studies demonstrated similar inflammatory responses within these organs in homozygous and heterozygous mice. The increased susceptibility of homozygous mice to infection with L. monocytogenes was not seen when homozygotes were immunized with a low dose of L. monocytogenes. Although the results were not as striking as with L. monocytogenes, homozygous mice were also found to be more susceptible to infection with Salmonella typhimurium than were heterozygous mice (P less than 0.05). Splenic mononuclear cells from homozygous mice demonstrated less responsiveness in vitro to the mitogens concanavalin A and phytohemagglutinin than did those from heterozygotes (P less than 0.05). These data suggest that there is a generalized defect in innate immunity in homozygous mice which makes them more susceptible to infection by L. monocytogenes and S. typhimurium. The site of this immunological defect is not known but is most likely in the mononuclear phagocyte and may be due to tissue iron overload.
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PMID:Resistance to infection in murine beta-thalassemia. 292 37

LGL leukemia results from a chronic, clonal proliferation of LGL. Chronic neutropenia with recurrent bacterial infection and splenomegaly are common clinical manifestations. Rheumatoid arthritis coexists in some of these patients, who thus resemble patients with Felty syndrome. Other hematologic abnormalities that may occur include pure red-cell aplasia and adult-onset cyclic neutropenia. Lymphoid infiltration of bone marrow, splenic red pulp cords, and hepatic sinusoids is characteristic; lymph node and skin involvement are rare. Multiple serologic abnormalities are frequently present, including positive tests for rheumatoid factor and/or antinuclear antibody, polyclonal hypergammaglobulinemia, and circulating immune complexes. Antineutrophil and antiplatelet antibodies are often present. Leukemic LGL exhibit phenotypic heterogeneity; the most common phenotype in our patients is CD2+, CD3+, CD8+, HNK-1+, CD16-. Despite markedly increased numbers of LGL, functional activity of the cells is usually decreased. The mechanism of cytopenias is uncertain: in pure red-cell aplasia, it appears to be due to suppressive effect on erythropoiesis by abnormal LGL, but in patients with chronic neutropenia it may be antibody-mediated. Although most patients appear to have a relatively benign clinical course, mortality from infections and progressive lymphoproliferation is substantial. Optimal therapy remains undefined. Some preliminary evidence suggests that LGL leukemia may be associated with infection with a retrovirus similar to HTLV-I. Although relatively rare, LGL leukemia is of interest because a better understanding of this disease process may contribute to our knowledge of autoimmune diseases, the immunoregulatory functions of LGL, and the mechanisms controlling normal hematopoiesis.
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PMID:Large granular lymphocyte leukemia. Report of 38 cases and review of the literature. 362 48

We describe a case of spontaneous bacterial peritonitis in a 53 year old man affected by cryptogenic micro-macronodular cirrhosis, portal hypertention, splenomegaly and hypersplenism, who was admitted with hepatic failure and septic shock and successfully treated with antibiotics (combination of clindamycin and netilmycin), surgical abdominal drainage and splenectomy. This case gave reason for a literature review and an update on the therapeutic options in these high risk patients, especially concerning the role of surgery. Spontaneous Bacterial Peritonitis (SBP) is defined as a bacterial infection of ascitic fluid in the absence of any septic focus. It is a typical life-threatening complication of hepatic cirrhosis with ascites. Mortality is very high and ranges from 75% to 97% of patients, due to septic shock and hepatic failure (hepatorenal syndrome, hepatic encephalopathy, gastrointestinal bleeding). Infection with a single organism is found in most cases. Gram negative bacilli are present in about 70% of cases and E. coli (less frequently Klebsiella, Serratia, Pseudomonas) is principally found. Gram positive cocchi comprise an additional 30% of cases. Anaerobic and microaerophilic organisms seem to be rare causes of SBP (2.7-6%); this finding is probably due to the intrinsic bacteriostatic activity of ascites, which contains high oxygen tension (70 mmHg) and is an inhospitable environment for bacteroides and Clostridia. The prevalent isolation of enteric organism suggest that the gut is the most frequent source of infection, even if the pathogenetic mechanism is not yet well known. The right treatment depends on differentiating primary (SBP) from secondary peritonitis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Is the surgical treatment of spontaneous bacterial peritonitis still up-to-date?]. 824 98

A follow-up study of 179 cases of human immunodeficiency virus (HIV) seropositive neonates born from HIV seropositive mothers is reported. At the time of the present study, HIV infection resulting from maternofetal transmission was found in 50 cases, while 108 infants were not infected; HIV infection remained uncertain in 16 cases; 5 infants were lost for follow-up. Out of the 50 infected cases, 20 were less than two-year old, 17 were 2-5 year old and 13 were older than 5 years. Very few remained asymptomatic after the age of 6 months, the most common symptoms being adenopathies and/or hepatomegaly and/or splenomegaly. Twenty-six had an acquired immunodeficiency syndrome (AIDS). Six died, from pneumocystosis (3), cytomegalovirus infection (1) and septicemia (2). Virus culture and polymerase chain reaction were the most efficient laboratory methods for early diagnosis of HIV infection, both being positive in more than 95% of the infected cases after the age of 3 months. A close clinical and biological supervision is recommended in these infants and children because of the permanent threat of infectious diseases in relation to their immunodeficiency. Treatment associates: 1) antiviral therapy with AZT as soon as the HIV infection is diagnosed; 2) primary prophylaxis against pneumocystosis with trimethoprim-sulfamethoxazol; 3) IV immunoglobulins in the case of repeated bacterial infection; 4) regular evaluation of the nutritional status and psychological assistance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Management of HIV-seropositive newborn infants. Personal experience apropos of 179 cases]. 839 76

Both interleukin-12 (IL-12) and tumor necrosis factor alpha (TNF-alpha) are produced early in intracellular bacterial infection. Depletion of either IL-12 or TNF-alpha by a single injection of specific antibody 4 h before the injection of Brucella abortus 19 led to the exacerbation of infection 2 weeks later. Whereas the effect of IL-12 depletion on resistance was persistent and exacerbation was still significant 6 weeks later, the bacterial numbers in mice depleted of TNF-alpha were similar to the bacterial numbers in control infected mice by 6 weeks postinfection. Massive splenomegaly, which is often seen in 2-week Brucella-infected mice, was not observed in IL-12- or TNF-alpha-depleted mice. Both IL-12- and TNF-alpha-depleted mice showed reduced cell accumulation in the spleen compared with the massive cell accumulation in control infected mice. Granuloma formation in livers was much reduced in IL-12-depleted mice but not in TNF-alpha-depleted mice. Gamma interferon (IFN-gamma) production by cells from TNF-alpha-depleted mice was not significantly different from that of cells from control infected mice. In contrast, the production of IFN-gamma by both CD4+ and CD8+ T cells from IL-12-depleted mice was greatly reduced, compared with that from control infected mice. This effect was still observed when the antibody injection was delayed for up to 7 days postinfection, but injections of anti-IL-12 antibody into mice with established Brucella infection had no significant effect on IFN-gamma production by T cells. Taken together, these results suggested that IL-12 contributed to resistance mainly via an IFN-gamma-dependent pathway and had a profound effect on the induction of acquired cellular resistance. In contrast, TNF-alpha was involved in resistance possibly via direct action on effector cells and may not be essential for the induction of acquired cellular resistance.
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PMID:Tumor necrosis factor alpha and interleukin-12 contribute to resistance to the intracellular bacterium Brucella abortus by different mechanisms. 869 8

Control of intracellular bacterial infections requires interferon-gamma (IFN-gamma) both for establishing a Th1 T-cell response and for activating macrophages to kill the bacteria. Exposure of mice deficient in IFN-gamma to mycobacterial infection produces an immune response characterized by a Th2 T-cell phenotype, florid bacterial growth, and death. We report here that IFN-gamma-deficient mice infected with mycobacteria also undergo a dramatic remodeling of the hematopoietic system. Myeloid cell proliferation proceeds unchecked throughout the course of mycobacterial infection, resulting in a transition to extramedullary hematopoiesis. The splenic architecture of infected IFN-gamma-deficient mice is completely effaced by expansion of macrophages, granulocytes, and extramedullary hematopoietic tissue. These features coincide with splenomegaly, an increase in splenic myeloid colony-forming activity, and marked granulocytosis in the peripheral blood. Systemic levels of cytokines are elevated, particularly interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF). These results suggest that in addition to its central role in cellular immunity, IFN-gamma may be a key cytokine in coordinate regulation of immune effector cells and myelopoiesis. This model should be valuable for deciphering the cross-talk between the immune response and hematopoiesis during bacterial infection and for improving our understanding of the mechanisms that control chronic infections.
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PMID:Hematopoietic remodeling in interferon-gamma-deficient mice infected with mycobacteria. 953 2

Lymphoproliferative disorders of large granular lymphocytes (LGL) can arise from either CD3+ T cells or CD3- natural killer cells. Polyclonal proliferation of LG lymphocytes is called LGL lymphocytosis, monoclonal proliferation of LG lymphocytes is LGL leukaemia. Prominent clinical manifestations of LGL lymphocytosis and leukaemia are bacterial infections, splenomegaly, and may be connected with rheumatic or autoimmune disorders. Hematologic findings reveal particularly lymphocytosis, and severe neutropenia. The beta chain gene of T cell receptor rearrangement analysis is necessary for distinguishing of T LGL lymphocytosis from T LGL leukaemia. The authors report a case of young woman with T cells LGL lymphroproliferative disorder, bacterial infection, reactive lymphadenopathy, and spontaneous regression of the lymphocytosis within 6 months.
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PMID:[Lymphocytosis with large granular lymphocytes: case report]. 1122 87


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