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)

Congenital neutropenias include a heterogenous group of diseases characterized by a decrease in circulating neutrophils. In phase I/II/III studies in patients with severe congenital and cyclic neutropenia, treatment with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) resulted in a rise in the absolute neutrophil counts (ANC) and a reduction in infections. We report the effects of long-term safety of subcutaneous r-metHuG-CSF administration in 54 patients (congenital n = 44. cyclic n = 10) treated for 4-6 years. A sustained ANC response was seen in 40/44 severe congenital neutropenia patients and 10/10 cyclic neutropenia patients. Two patients required an increase of > 25% in dose to maintain a clinical response; one patient became refractory to therapy. A significant decrease in the incidence of severe infections and the need for intravenous antibiotics was noted. Significant adverse events noted which may or may not be related to therapy included: osteopenia (n = 15), splenomegaly (n = 12), hypersplenism (n = 1), vasculitis (n = 2), glomerulonephritis (n = 1), BM fibrosis (n = 2), MDS/leukaemia (n = 3), and transient inverted chromosome 5q with excess blasts (n = 1). R-metHuG-CSF has been well tolerated in the majority of patients and resulted in a long-term improvement in their clinical status.
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PMID:Long-term safety of treatment with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) in patients with severe congenital neutropenias. 1093 Oct 6

A patient with chronic myeloproliferative disorder (CMPD) developed Sweet's syndrome during granulocyte colony-stimulating factor (G-CSF) therapy. A 61-year-old man with essential thrombocythemia was treated with busulfan intermittently since April, 1991. In February, 1993, hepatosplenomegaly with leukoerythroblastosis arose and a diagnosis of myelofibrosis with extramedullary hematopoiesis in the spleen was established. For alleviation of left hypochondralgia due to splenomegaly, he received splenic irradiation in September, 1993. Soon after the irradiation, his peripheral blood revealed pancytopenia and then administration of rhG-CSF was begun on the 9th of October, 1993. One week after G-CSF therapy, he became feverish and painful eruptions on the face and the upper extremities appeared and enlarged. Skin biopsy resulted in a diagnosis of Sweet's syndrome. Treatment with oral prednisone, 30 mg daily, was begun, and rapid and significant improvement of the skin lesions was obtained. The pathogenesis of Sweet's syndrome remains obscure, but careful follow up is necessary for patients during G-CSF therapy with respect to development of Sweet's syndrome.
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PMID:[Sweet's syndrome in a patient with chronic myeloproliferative disorder during recombinant human granulocyte colony stimulating factor therapy]. 754 Feb 25

A 66-year-old male experienced the sudden onset of amnesia and generalized convulsions, and during the subsequent month developed consciousness disturbance, disorientation, memory disturbance, abnormal speech and behavior, pseudobulbar palsy, unsteadiness and urinary/fecal incontinence. The initial brain CT scan was unremarkable, and the MRI findings were also unremarkable, except for evidence of several scattered lacunar strokes in the cerebral white matter. 99mTc-HM-PAO-SPECT, however, revealed multifocal large hypoperfused lesions in the cerebrum. The erythrocyte sedimentation rate and serum CRP, LDH and gamma-globulin levels were elevated. CSF studies showed mild pleocytosis and increased protein levels. The patient's subsequent course was marked by fever, SIADH, adrenal enlargement, splenomegaly, pulmonary infiltration and pancytopenia. The neurological signs progressively worsened, until the patient lapsed into an apallic state and died 3 months after the onset of symptoms. Autopsy disclosed diffuse intravascular B lymphomatous proliferation in the brain, lungs, kidneys, adrenals, spleen and pancreas. Until now, the brain SPECT findings of IL were not very well known, but in our patient, SPECT was capable of demonstrating the pathophysiologic changes very precisely. SPECT was able to provide valuable information on the pathophysiology of IL and may therefore become another powerful tool in the diagnosis of IL.
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PMID:[A case of intravascular lymphomatosis (IL) with diffuse cerebral hypoperfusion detected by SPECT]. 766 6

Recombinant human (rh) granulocyte-macrophage colony-stimulating factor (GM-SCF) is currently being tested in clinical trials for the treatment of acute myeloid leukemias with two main intentions: reduction of neutropenia and recruitment of leukemic blasts into cell cycle to enhance cytarabine (ara-C) mediated cytotoxicity. We report a case of a fatal spleen rupture in a patient with acute monocytic leukemia (AML M5b) who was treated according to a clinical phase I/II protocol with rh GM-CSF priming and standard induction chemotherapy TAD 9 (thioguanine/ara-C/daunorubicin). During treatment we observed rapidly rising peripheral blast counts and the development of an acute abdomen. Ultrasound examination revealed splenomegaly due to diffuse cellular infiltration and spleen rupture. The patient died 17 days later due to pneumonia and renewed spleen hemorrhage. Bone marrow progenitor assays before treatment showed exclusive growth of monocytoid blast cell colonies (CFU-L). Colony growth could be stimulated with rh GM-CSF and blocked dose-dependently by a monoclonal anti-GM-CSF antibody. CFU-L proliferation also increased after stimulation with rh interleukin-3 (rh IL-3) and supra-additively with rh granulocyte colony-stimulating factor (rh G-CSF) combined with rh GM-CSF. Furthermore, rh GM-CSF induced surface marker expression of CDw 65 and CD 11b on isolated CFU-L blasts. After short-term suspension culture, rh GM-CSF enhanced the expression of CD 29- and CD 11b-adhesion molecules on peripheral blast cells. In summary, this case represents a fatal spleen rupture occurring during rh GM-CSF priming and induction chemotherapy for acute monocytic leukemia. Although the etiology of this spleen rupture remains uncertain, in view of our data we suggest special caution, when further testing this therapy protocol in acute leukemias with monocytic subtype and high peripheral blast cell counts.
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PMID:Fatal spleen rupture during induction chemotherapy with rh GM-CSF priming for acute monocytic leukemia. Clinical case report and in vitro studies. 845 Jun 76

NF-ATp is a member of a family of genes that encodes the cytoplasmic component of the nuclear factor of activated T cells (NF-AT). In this study, we show that mice with a null mutation in the NF-ATp gene have splenomegaly with hyperproliferation of both B and T cells. They also display early defects in the transcription of multiple genes encoding cytokines and cell surface receptors, including CD40L and FasL. A striking defect in early IL-4 production was observed after ligation of the TCR complex by treatment with anti-CD3 in vivo. The transcription of other cytokines including IL-13, GM-CSF, and TNF alpha was also affected, though to a lesser degree. Interestingly, the cytokines IL-2 and IFN gamma were minimally affected. Despite this early defect in IL-4 transcription, Th2 development was actually enhanced at later timepoints as evidenced by increased IL-4 production and IgE levels in situations that favor the formation of Th2 cells both in vitro and in vivo. These data suggest that NF-ATp may be involved in cell growth, and that it is important for the balanced transcription of the IL-4 gene during the course of an immune response.
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PMID:Hyperproliferation and dysregulation of IL-4 expression in NF-ATp-deficient mice. 861 34

Seven patients, 3 men and 4 women 48-72 years of age and suffering from idiopathic myelofibrosis were given a combination of recombinant human erythropoietin (r-hu-Epo), interferon-alpha-2b (IFN) and GM-CSF, in an attempt to treat their pancytopenia and marrow fibrosis. The dose of r-hu-Epo was 200 U/kg 3 times weekly, that of IFN was 3 x 10(6)/U 3 times weekly, and that of GM-CSF was 250 micrograms/m2/daily. The duration of therapy ranged from 3 to 6 months for r-hu-Epo and IFN and was 3 weeks for GM-CSF. The treatment regimen had a beneficial effect on all patients. The levels of hemoglobin increased in all patients but particularly in 5 (2 of whom had been dependent on red blood cell transfusions). Splenomegaly decreased significantly in 4 patients. Fibrosis in the bone marrow decreased in 2 patients. Three patients also had an increase in the number of white blood cells during the therapy with GM-CSF. We observed mild side effects in 6 of our patients. One patient had severe side effects from IFN and treatment was discontinued. In conclusion, the combination of r-hu-Epo, IFN and GM-CSF may improve the anemia (due to r-hu-Epo), increase the white blood cell count (due to GM-CSF) and reduce the marrow fibrosis (probably due to IFN) in patients with idiopathic myelofibrosis.
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PMID:Combination therapy with recombinant human erythropoietin, interferon-alpha-2b and granulocyte-macrophage colony-stimulating factor in idiopathic myelofibrosis. 870 5

Two children with Kawasaki disease (KD), a girl 3 yrs. and a boy 2.5 yrs., were described. The children met all criteria for the diagnosis of KD (fever, conjunctivitis, oral changes, extremity changes, rash, lymphadenopathy), and other diseases were excluded. In both children or one of them other clinical and laboratory findings occasionally detected in KD were observed: arthralgia, hepatomegaly and splenomegaly, slight elevation of transaminases and bilirubin level, slight elevation of CSF pleocytosis, sterile pyuria and hematuria. Electrocardiograms revealed sinus tachycardia and transient disturbances of heart repolarization. In both children changes in blood morphology and biochemical disturbances typical for inflammatory processes were noted. Thrombocytosis was seen in the 2nd week of the illness in the child in whom platelet counts were controlled. The child in whom diagnosis of KD was established in the first week of symptoms was treated with acetylsalicylic acid along with an oral penicillin. A child with retrospectively diagnosed KD was treated with antibiotics and corticosteroids. Clinical and laboratory findings of KD resolved in both children within 4-6 weeks without complications from coronary blood vessels.
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PMID:[Mucocutaneous lymph node syndrome (Kawasaki disease) in 2 children]. 892 38

Recent studies support the importance of investigating a DNA vaccination approach for the immunologic control of HIV-1. In this regard, it may be important to specifically engineer immune responses in order to improve on first generation vaccine attempts. Especially for HIV, induction of cell-mediated immunity may be an important feature for any candidate vaccine. In an attempt to engineer in vivo the enhancement of cellular immune response and to direct Ag-dependent immune response from Th2 to Th1 type, we investigated the role of codelivery of genes for IL-12 and granulocyte-macrophage-CSF along with DNA vaccine formulations for HIV-1 Ag. We found that codelivery of IL-12 expression cassettes with DNA vaccines for HIV-1 in mice resulted in splenomegaly as well as a shift in the specific immune responses induced. The codelivery of IL-12 genes resulted in the reduction of specific Ab response, while the coinjection of granulocyte-macrophage-CSF genes resulted in the enhancement of specific Ab response. In addition, we observed a significant Ag-specific stimulation of T cells with codelivery of both cytokines. Most importantly, we observed a dramatic increase in specific CTL response from the group coimmunized with the HIV-1 DNA vaccine and IL-12 genes. This work demonstrates the power of DNA delivery in vivo for both the production of a new generation of more effective and targeted vaccines or immunotherapies as well as an analytic tool for the molecular dissection of the mechanisms of immune function.
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PMID:In vivo engineering of a cellular immune response by coadministration of IL-12 expression vector with a DNA immunogen. 899 99

Using a human melanoma/Scid xenograft model with the C8161, M24-met, LD-1 and other human melanoma lines to investigate spontaneous metastasis, we made the observation of marked splenomegaly (up to five times normal weight and size) in only those xenografts exhibiting high degrees of spontaneous metastasis. Evaluation of this revealed the cause to be massive myelopoiesis due to ectopic granulocyte/ colony-stimulating factor (G-CSF) production by the melanoma cells. Because of these observations linking G-CSF expression with metastasis of human melanoma, we decided to investigate the mechanism of this ectopic production. No gross amplification or rearrangement of the G-CSF gene could be detected as the basis for the increased transcriptional activity in any of these lines. Human-human somatic cell hybridization studies carried out between the metastatic C8161 and several different nonmetastatic non-G-CSF-expressing lines revealed, in addition to metastatic dominance, 3- to 10-fold enhancement of G-CSF transcription and expression in the fusions compared with C8161 itself. The suggestion of a trans-dominant mechanism was further supported by transfection studies with a human G-CSF promoter-CAT-reporter construct, which revealed 3- to 5-fold increased reporter activity in only those melanoma lines and hybrids expressing G-CSF. Furthermore, no obvious autocrine or paracrine effects of this ectopic G-CSF expression on the melanoma lines' growth or metastasis were apparent, as all of the G-CSF-expressing lines lacked the G-CSF receptor and injections of purified recombinant G-CSF exerted no stimulatory effects on their tumorigenicity, latency, growth, or metastasis in Scid mice. Thus, we advance the hypothesis that G-CSF expression is serving as a marker of a more generalized trans-dominant pathway linked to tumor progression and metastasis. This hypothesis has direct relevance to many human cancers where ectopic hormone or growth factor production occurs with no obvious autocrine or paracrine benefit to the tumor.
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PMID:Ectopic G-CSF expression in human melanoma lines marks a trans-dominant pathway of tumor progression. 906 Aug 33

32 cases (21 acute severe malaria and 11 chronic malaria syndrome), who developed unusual complications and/or manifestations are reported. The acute manifestations were unexplained tachypnoea 4, pulmonary oedema 5 and shock due to multiple organ dysfunction syndrome 3, melena 2 and E coli septicaemia in one. The other features were concomitant salmonellosis 2, meningitis 1, renal failure 3, hepatorenal syndrome 2, hepatitis like illness 7, neck stiffness with normal CSF 3, urticaria and subconiunctival haemorrhage 2 each, apyrexial spell with anaemia 4, thromocytopenia 3, and hypoglycaemia 3 (two pretreatment and one while on quinine in 5% glucose drip). The chronic syndrome noted were hyperreactive malaria syndrome (Tropical splenomegaly) 3, repeated haemolysis 2, chronic simple malaria with positive parasitaemia and normal Igm levels 4, and cerebellar ataxia with tremors 3. Bone marrow in these cases was hypercullular with increase plasma cells. Liver biopsy revealed lymphocytic infiltration. There was no case with permanent neurogical deficit. All patients with pulmonary oedema and multiple organ dysfunction died but chronic syndrome patients recovered fully. Early recoginition of atypical manifestation and prompt treatment will decrease the mortality and morbidity due to malaria.
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PMID:Unusual acute and chronic complications of malaria. 928 1


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