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)

In this study two groups of patients with acute Chagas' disease were identified. Group one consisted of five patients with apparent acute Chagas' disease. These patients showed symptoms and signals of an acute illness, such as high fever and enlarged spleen. One of these patients developed severe myocarditis and heart failure. Group two consisted of seven patients with inapparent acute Chagas' disease. This was a nonclinical entity, not perceived by the patient who did not seek medical care. The diagnosis was made by the shift of a serologic test which indicates the presence of immunoglobulin M antibodies to Trypanosoma cruzi. The patients with apparent acute Chagas' disease showed positive delayed-type skin response to T. cruzi antigen. Also, their leukocytes showed significant inhibition of migration in the presence of this antigen. By contrast, the patients with the inapparent acute Chagas' disease did not show positive delayed-type skin response to T. cruzi antigen and no significant inhibition was observed when their cells migrated in the presence of this antigen. Of interest, none of these patients was capable of developing contact sensitivity to 2,4-dinitrochlorobenzene. However, three out of five patients with the apparent acute disease and all the normal control subjects showed positive contact reaction after sensitization to this drug. The results of these experiments would suggest that the thymus-derived (T)-lymphocyte function is depressed in patients with the clinically inapparent acute Chagas' disease. This immunodepression seems to be acquired in the course of the T. cruzi infection because all patients showed positive delayed-type skin response to at least one ubiquitous microbial extract, thus indicating previously normal T-cell function. We hypothesize that T. cruzi antigens may directly stimulate T cells with the concomitant release of factors that might become supressive for T-cell responses. Furthermore, the suppressive effect might interfere with the T-cell response to other antigens, such as to 2,4-dinitrochlorobenzene.
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PMID:Acquired cell-mediated immunodepression in acute Chagas' disease. 10 95

A young man had a mild, slightly progressive pulmonary sarcoidosis. After 4 years he developed an acute disease with splenomegaly, anemia, marked elevation of ESR, hypercalcemia and mild renal insufficiency. The anemia and ESR elevation disappeared after splenectomy, whereas the hypercalcemia still needs corticosteroid treatment. Attempts to withdraw this treatment resulted in recurrence of the hypercalcemia, but no other abnormalities. In contrast to other organs examined, the sarcoid tissue in the spleen revealed necrosis formation, consistent with a recent process. A Kveim antigen preparation from the spleen was less potent than antigen from mediastinal lymph nodes. It is suggested that the acute phase of the disease involved mainly the spleen. Speculations about the possible role of infectious agent(s) are put forward.
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PMID:Acute phase of sarcoidosis with splenomegaly and hypercalcemia. Description of a case, including a report about splenectomy and the preparation and testing of a Kveim antigen from the spleen. 69 75

The natural history and haematological features of 18 patients with a chronic form of myelomonocytic leukaemia are described. The majority were elderly and, in this series, females predominated. Haematological prodomata, such as unexplained monocytosis, leucopenia, or thrombocytopenia were common, and the clinical onset was insidious. Splenomegaly was variable but tended to increase as the disease progressed. Anaemia was usually less than in the acute disease, unless compounded by iron deficiency. The blood film typically showed a mixed monocytosis and granulocytosis, cells in both lines showing abnormalities. 'Paramyeloid' cells, appearing in Romanowsky stained films intermediate between myelocytes and monocytes, were characteristic, although cytochemical and electron microscopical analysis suggests that these cells may be allotted to one or other cell line. The marrow aspirate was characteristically hypercellular, showed granulocytic hyperplasia, and, in contrast to the well-differentiated blood picture, the proportion of poorly differentiated cells, including blasts, was high. Serum lysozyme levels were usually raised. Five of the 18 cases survived more than 5 years, while 10 lived 2 years or longer. The morphological and clinical features form part of a spectrum including acute myelomonocytic leukaemia, into which several of the patients transformed. Recognition of the syndrome is important because the patients are probably best managed without intensive chemotherapy.
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PMID:Chronic myelomonocytic leukaemia. 105 74

Mice infected with LP-BM5 murine leukemia viruses develop a syndrome, termed mouse AIDS (MAIDS), characterized by increasingly severe immunodeficiency and progressive lymphoproliferation. Virus-infected mice were examined for the ability to resist acute infection and to control chronic infection with the protozoan Toxoplasma gondii, a major opportunistic pathogen of individuals infected with human immunodeficiency virus. Mice infected with the retroviruses for 2 or 4 weeks responded normally to challenge with the parasite, but mice inoculated with the protozoan 8 or 12 weeks after viral infection died with acute disease due to T. gondii. Increased sensitivity to acute infection was associated with a reduced ability to produce gamma interferon (IFN-gamma) and with established changes in CD4+ T-cell function. Mice latently infected with T. gondii and then inoculated with the retrovirus mixture were found to reactivate the parasite infection, with 30 to 40% of dually infected animals dying between 5 and 16 weeks after viral infection. Reactivation was associated with reduced proliferation and impaired production of IFN-gamma in response to stimulation with soluble T. gondii antigens or to concanavalin A. Continuing resistance to lethal reactivation in the remaining mice was shown to require CD8+ T cells and expression of IFN-gamma. In addition, it was found that chronic infection with T. gondii altered the course of MAIDS by inhibiting the progression of splenomegaly and immunodeficiency and reducing the expression of both the helper and etiologic defective viruses. These results support previous studies which indicate that infection with T. gondii is controlled by synergistic interactions between CD4+ and CD8+ T cells, the functions of which are progressively impaired during the course of MAIDS.
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PMID:Opportunistic infections and retrovirus-induced immunodeficiency: studies of acute and chronic infections with Toxoplasma gondii in mice infected with LP-BM5 murine leukemia viruses. 132 58

Trypanosoma cruzi may be transmitted to a susceptible human through different routes: a superficial lesion in the skin, such as a scraping of the small wound produced by the hematophagous triatomid bug vector, which becomes infected with its contaminated feces; the placenta, from the infected mother to the product of conception; a transfusion from an infected donor, or even by ingestion of diverse foods infected or contaminated with the parasite. Whichever may be the transmission of the protozoon, it is advisable to have in mind that it is able to produce an asymptomatic or a symptomatic infection, being possible in both cases, using appropriated methods, to detect the T. cruzi and/or the antibodies generated. From the clinical stand-point, Chagas' Disease may present itself as acute or as a chronic disease. Habitually, the acute disease is characterized by general involvement, fever, hepato-splenomegaly, polidenopathy, and occasionally myocarditis and/or encephalitis, whereas, the chronic form of the disease is characterized by presenting itself in an isolated way or combined, chronic myocardiopathy, megaesophagous or megacolon. At any rate, the problems center in the possibility of a reasonable diagnostic assurance which permits the adoption of adequate therapeutic measures. Some facts, which may help to confront these problems are: a) The epidemiological antecedents (origin in an endemic area, personal knowledge of the vector or of being bitten by it, whether the mother or other relatives are affected by the disease, etc.).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Problems related to the diagnosis of Chagas' disease]. 251 14

The serum concentration of laminin P1 antigen was determined in 32 patients with various myeloproliferative disorders, including 19 patients with idiopathic myelofibrosis. The serum concentration of the aminoterminal propeptide of type III procollagen (PIIINP) was measured concomitantly in 27 patients. Serial laminin measurements were carried out in 25 patients. The median serum laminin concentration in patients with acute disease, i.e. acute myelofibrosis and patients in a transforming disease phase was significantly higher (1.58 U/ml; range 1.15-2.07) as compared with patients with chronic disease (1.02 U/ml; range 0.75-1.76; p = 0.012) and healthy control subjects (1.13 U/ml; range 0.75-1.67; p = 0.00015). In individual patients serum laminin covariated closely with serum PIIINP, the leucocyte count and LDH. The median serum laminin concentration in patients with a huge spleen was significantly lower than in the patient group with a normal spleen size/previous splenectomy. Pronounced splenomegaly was particularly prevalent in patients with chronic disease implicating splenic enlargement as a significant extrahepatic site of laminin uptake/degradation in myeloproliferative disorders.
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PMID:Serum laminin P1 in idiopathic myelofibrosis and related diseases. 806 64

Cluster outbreaks of lymphoma and leukemia have been associated with viral infections in many species including humans, cattle, and cats. This study describes epidemiological, clinical, and pathological features of cluster outbreaks of lymphoma in multiferret households and examines and compares the Aleutian disease virus (ADV) and feline leukemia virus (FeLV) status of cases, ferrets at risk, and controls. Three ferret groups with 21 cases of histologically diagnosed lymphoma (12.6% cumulative incidence) and their cohabitants (n = 35) were examined and compared with three control groups (n = 52) of cohabitating ferrets without lymphoma. A familial distribution was observed in one group but most cases were not consanguinous. Ferrets greater than 3 years of age developed chronic disease in two of the groups and 2-year-old adults had acute disease in the remaining group. Lymphocytosis, splenomegaly, and lymphadenopathy were prominent features. Histologically, predominantly small noncleaved cell and polymorphous lymphoid lesions were observed. All of the ferrets with lymphoma that were tested for ADV and FeLV using serology or PCR were negative. The rate of ADV antibody among cases or ferrets at risk was not significantly different from controls. None of the cluster ferrets were seropositive for FeLV p27 antigen using a monoclonal ELISA. Infection with a novel ferret virus is suspected, but an etiological agent has not yet been identified.
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PMID:Clusters of lymphoma in ferrets. 863 Jun 83

A retrospective and transversal study of our patients with portal cavernomatosis is developed, with the aim of comparing the evolution and the present status of the patients that have undergone different therapeutical approaches. Between 1975 and 1995, 15 patients with portal cavernomatosis have been treated. Personal history, signs and symptoms at the moment of diagnosis, and treatment were analyzed. Now, the controls have been made by physical examination and ECO-Doppler of the espleno-portal system. In 6 cases the absence of bleeding made surgery unnecessary. In the 9 patients with digestive haemorrhage, it could be controlled pharmacologically, with a later surgical approach. Now, all non-operated and 6 operated patients show splenomegaly, without bleeding. The ECO-Doppler shows colateral flow, the splenomegaly in the non-operated and the surgical shunts and the hepatofugal circulation in the operated patients. Looking at our results, we believe that prophylactic surgery is not indicated. In those cases of digestive bleeding, surgery after the complete resolution of the acute disease shows good results at a short and long term.
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PMID:[Our experience in portal cavernomatosis in childhood: cross-sectional study and analysis of results]. 937 40

The high resistance to malaria in the nomadic Fulani population needs further understanding. The ability to cope with multiclonal Plasmodium falciparum infections was assessed in a cross-sectional survey in the Fulani and the Dogon, their sympatric ethnic group in Mali. The Fulani had lower parasite prevalence and densities and more prominent spleen enlargement. Spleen rates in children aged 2-9 years were 75% in the Fulani and 44% in the Dogon (P<0.001). There was no difference in number of P. falciparum genotypes, defined by merozoite surface protein 2 polymorphism, with mean values of 2.25 and 2.11 (P=0.503) in the Dogon and Fulani, respectively. Spleen rate increased with parasite prevalence, density and number of co-infecting clones in asymptomatic Dogon. Moreover, splenomegaly was increased in individuals with clinical malaria in the Dogon, odds ratio 3.67 (95% CI 1.65-8.15, P=0.003), but not found in the Fulani, 1.36 (95% CI 0.53-3.48, P=0.633). The more susceptible Dogon population thus appear to respond with pronounced spleen enlargement to asymptomatic multiclonal infections and acute disease whereas the Fulani have generally enlarged spleens already functional for protection. The results emphasize the importance of spleen function in protective immunity to the polymorphic malaria parasite.
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PMID:Spleen enlargement and genetic diversity of Plasmodium falciparum infection in two ethnic groups with different malaria susceptibility in Mali, West Africa. 1629 5

Systemic lupus erythematosus (SLE) is a complex, systemic autoimmune disease with a diverse range of immunological and clinical manifestations. The introduction of broad spectrum immunosuppressive therapies and better management of acute disease exacerbations have improved outcomes for lupus patients over recent years. However, these regimens are burdened by substantial toxicities and confer significantly higher risks of infection, thus there remains a significant and unmet medical need for alternative treatment options, particularly those with improved safety profiles. Heat shock protein 90 (HSP90) is a ubiquitously expressed molecular chaperone that acts as an important modulator of multiple innate and adaptive inflammatory processes. Of note, accumulating clinical and experimental evidence has implicated a role for HSP90 in the pathogenesis of SLE. Here we evaluated the potential of HSP90 as a therapeutic target for this disease using the selective small molecule inhibitor ganetespib in the well-characterized MRL/lpr autoimmune mouse model. In both the prophylactic and therapeutic dosing settings, ganetespib treatment promoted dramatic symptomatic improvements in multiple disease parameters, including suppression of autoantibody production and the preservation of renal tissue integrity and function. In addition, ganetespib exerted profound inhibitory effects on disease-related lymphadenopathy and splenomegaly, and reduced pathogenic T and B cell lineage populations in the spleen. Ganetespib monotherapy was found to be equally efficacious and tolerable when compared to an effective weekly dosing regimen of the standard-of-care immunosuppressive agent cyclophosphamide. Importantly, co-treatment of ganetespib with a sub-optimal, intermittent dosing schedule of cyclophosphamide resulted in superior therapeutic indices and maximal disease control. These findings highlight the potential of HSP90 inhibition as an alternative, and potentially complementary, strategy for therapeutic intervention in SLE. Such approaches may have important implications for disease management, particularly for limiting or preventing treatment-related toxicities, a major confounding factor in current SLE therapy.
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PMID:The HSP90 Inhibitor Ganetespib Alleviates Disease Progression and Augments Intermittent Cyclophosphamide Therapy in the MRL/lpr Mouse Model of Systemic Lupus Erythematosus. 2597 40


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