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)

A retrospective analysis of the clinical and haematological characteristics of patients diagnosed as having juvenile chronic granulocytic leukaemia between 1971 and 1986 was carried out. Thirty-three children were identified who were between the ages of 18 weeks and 8.8 years at diagnosis. The disease was more frequent in boys than girls (23:10). The most common presenting symptoms were skin rash (58%) and bleeding manifestations (45%). All patients had some degree of splenomegaly and in 88% this was more than 3 centimetres below the costal margin. Hepatomegaly and lymphadenopathy were also frequent findings. Anaemia was common and leucocytosis an invariable finding with a white cell count above 50 x 10(9) 1-1 in 42%. Monocytosis was found in 78%. Haemoglobin F measurements were available in 31 children and above 10% in 22 (67%). No child had the Philadelphia chromosome or monosomy 7. Thirty children were treated with chemotherapy, with a variable degree of symptomatic improvement. Twenty-nine patients had died with a median survival time of 5 months. The commonest cause of death was complications of bone marrow failure and no child developed acute leukaemia. Presenting characteristics associated with a longer survival period were age less than 6 months (P = 0.02), female sex (P = 0.02), HbF less than 10% (P = 0.0004) and the absence of bleeding manifestations (P = 0.03). We conclude that the prognosis for children aged over 6 months, with a raised HbF level is very poor, and that, in the absence of possible bone marrow transplantation, consideration should be given to novel treatment approaches for these patients.
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PMID:Prognostic factors in juvenile chronic granulocytic leukaemia. 138 Feb 83

Splenomegaly associated with myelodysplastic disorders in children may be massive and can result in pancytopenia, abdominal discomfort, and respiratory distress. When these symptoms cannot be relieved by nonsurgical means, splenectomy may be indicated. Under such conditions, surgical splenectomy carries increased risks, as the thrombocytopenia is difficult to correct secondary to splenic sequestration. Additionally, the surgical anatomy is often distorted secondary to the massive spleen and dissection can be difficult. These factors can lead to uncontrollable hemorrhage. In an attempt to decrease intraoperative blood loss, the authors successfully performed preoperative splenic artery embolization in 11 of 12 children (age range, 1-11 years) with pancytopenia due to hypersplenism. Hypersplenism requiring surgical splenectomy was due to leukemia (n = 9), myelodysplastic syndrome (n = 1), immune thrombocytopenia (n = 1), and osteopetrosis (n = 1). Embolization was performed under general anesthesia, prior to surgery, with gelatin sponge particles alone, Gianturco coils alone, or a combination of polyvinyl alcohol sponge particles and Gianturco coils. Embolization allowed for safe surgical splenectomy.
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PMID:Preoperative embolization of the spleen in children with hypersplenism. 144 26

A variant strain of Rauscher leukemia virus (RLV-A) obtained from a transplantable murine monomyelocytic leukemia causes a disease characterized by frank anemia, wasting, hepatosplenomegaly and erythroblastosis. The involvement of platelets in this disease are reported here. The RLV-A induced a severe thrombocytopenia (25 percent of control level) at the terminal stage of disease. This thrombocytopenia was not associated with disseminated intravascular coagulopathy since the prothrombin times were always within normal limits. The partial thromboplastin time was elevated in the terminal stages of disease and was found to be associated with factor deficiencies, possibly owing to the presence of anti-factor antibodies, in the intrinsic coagulation pathway, especially factor VIII. Further, splenectomy did not abolish the thrombocytopenia, since splenectomized, virally infected animals also developed severe thrombocytopenia (29 percent of control levels). The ensuing splenomegaly during progression of disease was not the cause of the thrombocytopenia. A physiological response to the severe thrombocytopenia was the production of larger size platelets. At terminal stages of the disease, platelet volume increased to 4.2 mu 3 (normal is 3.0 mu 3). An increase in platelet volume was also observed in splenectomized, virally infected animals. Electron microscopy indicated that these circulating platelets contained c-type viral particles. Viral infection was associated with decreased life span of circulating platelets, as measured by 75Se-methionine at mid and terminal stages of the disease. Our results suggest that direct viral infection of platelets and/or megakaryocytes with subsequent cell lysis is a possible cause of the observed thrombocytopenia observed in RLVA-induced disease and may also occur in other retrovirally-induced diseases.
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PMID:Thrombocytopenia in a retrovirally-induced murine erythroleukemia. 145 28

Sixty-day bioassays of iodinated glycerol, trichlorfon, and acetaminophen were conducted using a leukemia transplant model in 6- to 8-week-old F344 rats to investigate the potential of these chemicals to affect tumor progression. The chemicals were administered in the drinking water at doses that approximated those used in previously conducted 2-year carcinogenesis studies. Simultaneous with dose administration, half of a group of young, healthy, syngeneic rats were given subcutaneous transplants of mononuclear cells derived from spleens of leukemic donors. Variables used to quantitate tumor progression included body weight, spleen weight, white blood cell (WBC) and red blood cell (RBC) counts, packed cell volume, hemoglobin concentration, and platelet counts. Iodinated glycerol at 1.25 or 2.5 mg/ml caused a greater increase in leukocytosis in dosed transplant recipients in comparison to that experienced by undosed recipients: trichlorfon at 2.5 or 5.0 mg/ml enhanced splenomegaly and induced greater reductions in RBC parameters in dosed recipients in comparison to that experienced by undosed recipients. Acetaminophen at 3.0 and 6.0 mg/ml resulted in insignificant but dose-related increases in spleen weight and leukocytosis only in the female rat transplant recipients, as was observed in 2-year studies. Based on results from the short-term leukemia transplant model, data from 2-year carcinogenicity studies, and structure-activity considerations, exposure to iodinated glycerol and trichlorfon was more strongly associated with the expression of leukemia than exposure to acetaminophen. The potential carcinogenicity of each of these chemicals should be taken into consideration when calculating estimates of risk and decisions for their use.
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PMID:The effects of iodinated glycerol, trichlorfon, and acetaminophen on tumor progression in a Fischer rat leukemia transplant model. 145 7

A proportion of syngeneic female rats inoculated intramuscularly with a lethal T-cell lymphoblastic (Roser) leukaemia are cured by a single intraperitoneal injection of bischloroethylnitrosourea (BCNU) (Carmustine) (10 mg kg-1) given towards the end of the preleukaemic phase (day 7). Additional therapy on day 4, using intravenous leukaemia cells lethally labelled with the radionuclide 114Inm, enhanced the overall cure rate by 30%. The spleen is a major site of indium concentration from the targeting cells so that the continuous local radiation field appears to result in a substantial reduction of the body load of leukaemia cells in the enlarged spleen particularly, thus enhancing the curative potential of the drug. The results demonstrate in principle that in patients in remission a single dose of targeted radiotherapy in the spleen combined sequentially with an appropriate drug might provide considerable aid in eliminating a residual population of leukaemia cells.
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PMID:Cell-targeted 114Inm and drug (BCNU) combination therapy in a rat acute lymphoblastic leukaemia. 151 24

High sequence variability in the envelope gene of human immunodeficiency virus has provoked interest in nonenvelope antigens as potential immunogens against retrovirus infection. However, the role of core protein antigens encoded by the gag gene in protective immunity against retroviruses is unclear. By using recombinant vaccinia viruses expressing the Friend murine leukemia helper virus (F-MuLV) gag gene, we could prime CD4+ T-helper cells and protectively immunize susceptible strains of mice against Friend retrovirus infection. Recovery from leukemic splenomegaly developed more slowly after immunization with vaccinia virus-F-MuLV gag than with vaccinia virus-F-MuLV env; however, genetic nonresponders to the envelope protein could be partially protected with Gag vaccines. Class switching of F-MuLV-neutralizing antibodies from immunoglobulin M to immunoglobulin G after challenge with Friend virus complex was facilitated in mice immunized with the Gag antigen. Sequential deletion of the gag gene revealed that the major protective epitope was located on the N-terminal hydrophobic protein p15.
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PMID:Protection against Friend retrovirus-induced leukemia by recombinant vaccinia viruses expressing the gag gene. 153 53

We have followed for 33 months the changes that occurred in natural killer (NK) cell numbers and activity in a patient (A) with hairy cell leukaemia (HCL), using a single cell assay and a microcytotoxicity assay. The composition of the peripheral blood mononuclear cell population and malignant cell phenotype were also analysed. During this period he received treatment with interferon and his grossly enlarged spleen was removed. Four further patients were also studied, two were splenectomized and all had received treatment with interferon. In four of the five patients studied there was an apparent link between low NK activity and presence of a tumour-infiltrated spleen, and in the fifth patient, who was aleukemic and had no splenomegaly, NK function was related to disease activity. There was no correlation between NK activity and the number of target binding (TB) cells in these five patients. IFN had little direct effect on overall NK activity, but the proportion of killing cells among TB cells was increased. Three patients showed binding of several cells to a single target. Further analysis revealed that in the patients most of the TB cells were not CD56-positive NK cells, in contrast to TB cells from normal subjects. In patient A a large proportion (84%) of TB cells were identified as malignant cells and in patient E 15% of TB cells were malignant cells. The phenotype of the malignant cells was: CD19+, HLA-DR+ and CD25(Tac)+, except for patient A. In this patient the hairy cells were positive for the NK marker CD56 as well as the monocyte marker CD14. Furthermore, a change occurred in phenotype as only later samples carried CD25. It is concluded that the level of NK function correlates closely with disease activity in HCL and that competitive target cell binding by malignant cells may be one cause of depressed NK-cell function in hairy cell leukaemia.
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PMID:Natural killer cell function and malignant cell phenotype in hairy cell leukaemia. 153 17

The Philadelphia (Ph1) chromosome is a specific structural abnormality in which the abl oncogene is activated due to the formation of the novel chimeric gene, bcr/abl. To investigate the clinicopathological role of bcr/abl in Ph1-positive chronic myelogenous leukaemia (CML), we studied the clonal origin of haematopoietic progenitors by detecting bcr/abl mRNA in a single haematopoietic colony using the polymerase chain reaction (PCR). Nine patients with CML were examined. In 5 chronic phase patients, all granulocyte/macrophage (CFU-GM) and erythroid (BFU-E) progenitor-derived colonies were positive for bcr/abl mRNA. Colonies in which the transcripts were not detectable were observed in 4 patients. These 4 patients included one patient with a normal karyotype and without splenomegaly, a patient with cyclic oscillation of her white blood cell level, a patient treated with busulfan and interferon-alpha (INF-alpha), and a patient relapsing after allogenic bone marrow transplantation (BMT). Our observations indicate that detection of Ph1-positive clones by PCR may be used to evaluate clinical stages and the effects of treatment in CML.
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PMID:Analysis of clonality at the level of progenitors in chronic myelogenous leukaemia using the polymerase chain reaction. 156 40

The clinico-haematological and evolutive features of five patients with Ph'-positive chronic myelogenous leukaemia (CML) whose initial profile suggested the diagnosis of essential thrombocythaemia (ET) were analysed. The patients were women with severe thrombocytosis (greater than or equal to 1000 x 10(9)/L) and moderate leucocytosis (less than 25 x 10(9)/L), and only two of them had splenomegaly. Increased basophil count in peripheral blood was present in all cases, and peripheral myelocytosis was seen in three. The molecular analysis showed rearrangement of the BCR gene in the three patients on which it was performed. Increasing leucocyte count was seen in the three patients with extended follow-up, this reaching values in accordance with CML. Finally, the three patients who died suffered a blastic crisis. The analysis of this series, along with others reported in the literature, suggests that such cases correspond to atypical forms of CML rather than actual TE patients.
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PMID:[Chronic myeloid leukemia beginning as thrombocythemia. Analysis of 5 cases]. 158 31

Polycythemia vera (PV) is one of the myeloproliferative diseases, and, as such, is an example of clonal hematopoiesis. The progeny of a single, abnormal, hematopoietic stem cell gain a growth advantage over their normal counterparts resulting in overproduction of red cells generally accompanied by overproduction of granulocytes and platelets as well. There are a variety of nonspecific symptoms at onset related to the increased red cell mass and hematocrit accompanied by the more specific manifestations of pruritus, erythromelalgia, and hepatic, portal, and mesenteric vein thrombosis. Splenomegaly and hypertension are common. The laboratory hallmark is an increased red cell mass. There is also often an increase in white cell count, platelet count, and leukocyte alkaline phosphatase along with other findings reflecting the increased rate of turnover of hematopoietic cells. The bone marrow biopsy generally displays hypercellularity involving all three cell lines and absent iron stores. The diagnosis of PV depends on excluding spurious polycythemia in which there is a high hematocrit but a normal red cell mass and secondary polycythemia in which there is an increased red cell mass in response to tissue hypoxia or the inappropriate production of erythropoietin, generally by a tumor. In addition, one should try to establish the diagnosis in a positive fashion by a combination of studies of the blood and bone marrow. Phlebotomy and occasionally plateletpheresis should be used as acute therapy. Chronic therapy is guided by the knowledge that patients treated with phlebotomy alone have an increased rate of thrombotic complications particularly in older patients and those with previous thrombotic disease. Myelosuppressive therapy can reduce the incidence of these complications, but is commonly associated with an increased incidence of second malignancies, particularly acute leukemia. At present, hydroxyurea is the myelosuppressive agent of choice. Antiplatelet agents have a limited role except in the palliation of the syndrome of erythromelalgia. Median survival is approximately 10 years. As implied above, the causes of morbidity and mortality vary with the mode of chronic therapy which has been employed, leukemia being more common after myelosuppressive therapy and thrombotic complications being more common after therapy with phlebotomy alone. Ten percent to 50% of patients move into a spent phase followed by postpolycythemic myeloid metaplasia, irrespective of previous therapy employed. Eventually, the major problems may be cytopenias and massive splenomegaly.
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PMID:Polycythemia vera. 158 7


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