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

Myelofibrosis with myeloid metaplasia (MMM) is a collective term that describes the related disorders AMM, PPMM, and PTMM. The chronic myeloid disorders include chronic myeloid leukemia, polycythemia vera, essential thrombocythemia, and agnogenic myeloid metaplasia (myelofibrosis). These disorders display varying propensities for pathologic enlargement of the spleen which can lead to mechanical discomfort, hypercatabolic symptoms, anemia, thrombocytopenia, and portal hypertension. Splenectomy has been found to be of little benefit in the early stages of chronic myeloid leukemia. Similarly, the benefit of splenectomy in advanced cases is limited to symptomatic palliation and treatment of delayed engraftment after allogeneic bone marrow transplantation. Although polycythemia vera and essential thrombocythemia are also characterized by splenomegaly, splenectomy is not considered a therapeutic option in the absence of transformation of the disease into myelofibrosis with myeloid metaplasia. Splenectomy has been studied most in myelofibrosis with myeloid metaplasia. Although there is no clear survival advantage to splenectomy in this disorder, the surgical procedure can result in substantial palliation of mechanical discomfort, hypercatabolic symptoms, portal hypertension, and anemia. However, the procedure is associated with an approximately 9% mortality rate, and the postsplenectomy occurrence of extreme thrombocytosis, hepatomegaly, and leukemic transformation is of major concern.
 ...
PMID:Splenectomy in chronic myeloid leukemia and myelofibrosis with myeloid metaplasia. 1098 48

A 45-year-old Japanese woman with splenomegaly and thrombocytopenia was referred to our hospital. The diagnosis of Osler-Weber-Rendu disease (Osler's disease) was made because of spotty telangiectasia on her tongue, recurrent epistaxis since childhood, and a diathesis indicated by her family history. The patient's laboratory examination revealed anemia, thrombocytopenia, and other data consistent with chronic disseminated intravascular coagulation (DIC). Bone marrow examination was normal. Abdominal computed tomography showed marked enlargement of the spleen with deformity and calcified plaque, not homogeneously enhancing. Hypersplenism was not observed. Platelet scintigraphy indicated a remarkable uptake in the spleen. She was diagnosed as having chronic DIC associated with vascular lesions of Osler's disease in the spleen. Splenectomy was performed and the subsequent pathological findings indicated that fragility of the fine vascular architecture of the splenic red pulp might have been responsible for pathogenesis. The large pooling of blood with coagulation was thought to be secondary.
 ...
PMID:Splenomegaly and chronic disseminated intravascular coagulation in Osler-Weber-Rendu disease: a case report. 1107 62

It has been suggested that HIV plays a role in the generation of myeloproliferative disorders, including polycythemia vera (PV). Seven cases of polycythemia in HIV patients have been described in the literature, but only 3 of these met criteria for determining a primary origin (vera) of polycythemia. We report a case of PV in a patient infected with HIV. A 45 year old non-smoking homosexual male presented with 15.7 g/dl hemoglobin in 1991, and was diagnosed with HIV. After 7 years, he presented with plethora, splenomegaly, an erythrocyte mass of 71 ml/kg, and an oxygen saturation of 93.9% (the latter three constituting the major criteria for the diagnosis of PV). Erythrocytes 7.35 x 10(6)/ml hemoglobin, 21.4 g/dl, hematocrit 63%, leukocytes 12,400, erythropoietin < 5 nmoll/ml. These values are all compatible with a diagnosis of PV. The CD4 count was 321 cells/mm(3) and HIV viral load was undetectable. The patient was initially treated with zidovudine. He was then treated with didanosine, lamivudine, and saquinavir, but all of them failed to slow the increase in erythrocyte levels. After a diagnosis of PV, he was treated with hydroxyurea and phlebotomy, which normalized the hemogram. CD4 count rose to 474 cells/mm(3) and HIV viral load remained at undetectable levels. The patient remains in stable condition with combination treatment after 1 year. We suggest that this is a case of HIV infection which may have led to the emergence of polycythemia vera. Treatment of the HIV did not prevent the appearance of the myeloproliferative disorder.
 ...
PMID:Polycythemia vera in a patient with the human immunodeficiency virus: a case report. 1118 68

There is no single diagnostic marker for the only known type of primary acquired erythrocytosis, polycythemia vera (PV). The Polycythemia Vera Study Group (PVSG) used a combination of major and minor diagnostic criteria. However, these guidelines have some limitations and in the presence of newer diagnostic tools, have been re-evaluated. The recommendations of the Radionuclide Panel of the International Council for Standardization Hematology based on surface area are recommended over red blood cell mass (RCM) mL/kg expressions. Absolute erythrocytosis can be assumed in males and females with packed cell volume (PCV) values greater than 0.60 and greater than 0.56, respectively. A satisfactory strategy of investigation for a secondary erythrocytosis must be used. Hypoxemia, as well as renal and hepatic pathology, must be excluded. In unexplained absolute erythrocytoses, pO(2)(50) values and serum erythropoietin (EPO) levels should be examined. The latter can be disappointing in the confirmation of a secondary erythrocytosis, but elevated values contraindicate a diagnosis of a primary erythrocytosis. Establishment of a clonal marrow population supports a diagnosis of PV. Thus an acquired karyotypic abnormality is a major criterion. Palpable splenomegaly remains an important diagnostic marker. Scanning techniques to demonstrate splenic enlargement should be used with caution. Allowance must be made for interobserver and intraobserver differences and variation in normal spleen size with age and size of the subject. Splenomegaly demonstrated in this way should be taken as a minor criterion. An increased neutrophil count (>10 x 10(9)/L and >12.5 x 10(9)/L in smokers) is readily measurable and should replace total white blood cell count. The error in measurement of neutrophil alkaline phosphatase (NAP) score is large, making it an unsuitable diagnostic criterion. Neutrophil and platelet counts (>400 x 10(9)/L) should be taken as separate minor criteria. Endogenous erythroid colonies (EEC) grown from the peripheral blood have been used as a marker of PV, but it is an expensive technique that is not standardized and not totally specific for PV. Low serum EPO values found in the majority of patients with PV should hold a linked minor criterion position with EEC. Expert opinions should be obtained if bone marrow histology is to be used in the diagnosis of PV, but histology holds an important role in confirming the diagnosis. Semin Hematol 38(suppl 2):21-24.
 ...
PMID:Evaluation of diagnostic criteria in polycythemia vera. 1124 98

This review focuses on polycythemia vera (PV)-its diagnosis, cellular and genetic pathology, and management. In Section I, Dr. Pearson, with Drs. Messinezy and Westwood, reviews the diagnostic challenge of the investigation of patients with a raised hematocrit. The suggested approach divides patients on their red cell mass (RCM) results into those with absolute (raised RCM) and apparent (normal RCM) erythrocytosis. A standardized series of investigations is proposed for those with an absolute erythrocytosis to confirm the presence of a primary (PV) or secondary erythrocytosis, with abnormal and normal erythropoietic compartments respectively, leaving a heterogenous group, idiopathic erythrocytosis, where the cause cannot be established. Since there is no single diagnostic test for PV, its presence is confirmed following the use of updated diagnostic criteria and confirmatory marrow histology. In Section II, Dr. Green with Drs. Bench, Huntly, and Nacheva reviews the evidence from studies of X chromosome inactivation patterns that support the concept that PV results from clonal expansion of a transformed hemopoietic stem cell. Analyses of the pattern of erythroid and myeloid colony growth have demonstrated abnormal responses to several cytokines, raising the possibility of a defect in a signal transduction pathway shared by several growth factors. A number of cytogenetic and molecular approaches are now focused on defining the molecular lesion(s). In the last section, Dr. Barbui with Dr. Finazzi addresses the complications of PV, notably thrombosis, myelofibrosis and acute leukemia. Following an evaluation of published data, a management approach is proposed. All patients should undergo phlebotomy to keep the hematocrit (Hct) below 0.45, which may be all that is required in those at low thrombotic risk and with stable disease. In those at high thrombotic risk or with progressive thrombocytosis or splenomegaly, a myelosuppressive agent should be used. Hydroxyurea has a role at all ages, but (32)P or busulfan may be used in the elderly. In younger patients, interferon-alpha or anagrelide should be considered. Low-dose aspirin should be used in those with thrombotic or ischemic complications.
 ...
PMID:A Polycythemia Vera Updated: Diagnosis, Pathobiology, and Treatment. 1170 35

A case of a 12-year-old girl presenting with headache and splenomegaly and fulfilling the diagnostic criteria of polycythemia vera is reported. Her peripheral blood values were as follows: hemoglobin 18 g/dL, red blood cells 7,000,000/mm3, while blood cells 22,000/mm, and platelets 1,248,000/mm3. Phlebotomy was performed initially but was ineffective. Afterward 100 mg/kg per day aspirin and 30/mg/kg per day hydroxyurea were given. The patient has been asypmtomatic for 1 year and her recent hemoglobin level is 15.5 g/dL, platelet count 922,000/mm3, and white blood cell 12,800/mm3. Polycythemia vera is an extremely uncommon disease in childhood and for this reason its treatment is not well established.
 ...
PMID:Polycythemia vera in a 12-year-old girl: a case report. 1205 93

IgA nephropathy (IgAN) is one of the most frequent forms of glomerulonephritis (GN). However, its association with polycythemia vera (PV) has rarely been described. We report a case of IgAN combined with PV. The patient was a 46-year-old male with chronic renal failure, heavy proteinuria and erythrocytosis. He also presented hypertension and hematuria as well as splenomegaly, high arterial oxygen saturation and elevated leukocyte alkaline phosphatase activity. Possible causes of secondary erythrocytosis were ruled out. The renal biopsy revealed mesangial proliferative GN with predominant IgA deposition in mesangium. He was diagnosed as having IgAN and PV concomitantly. After administration of hydroxyurea, enalapril and felodipine, blood cell count and blood pressure normalized, while azotemia persisted. There was also a partial remission of the heavy proteinuria. We describe a case of IgAN associated with PV, and possible pathophysiologic relationships between two diseases are discussed with review of the literature.
 ...
PMID:IgA nephropathy in a patient with polycythemia vera. Clinical manifestation of chronic renal failure and heavy proteinuria. 1216 77

Diagnosis of essential thrombocythemia (ET) has been usually established by regarding the criteria of the Polycythemia Vera Study Group. Accordingly, a retrospective clinicopathological study was performed on 120 patients with a follow-up ranging between 5 and 13 years and repeated bone marrow trephine examinations. Following the new WHO classification, at presentation patients revealed three distinctive patterns of bone marrow (BM) features: (true) ET in 43 patients, prefibrotic idiopathic myelofibrosis (IMF) in 50 patients, and early IMF in 27 patients. Heterogeneity of morphological features was associated with correspondingly expressed laboratory data. Contrasting initial and early IMF, patients with true ET displayed an about 80% probability to lack splenomegaly, anemia, and increase in the LDH and LAP values and also failed to show any myeloblasts or erythroblasts on the peripheral blood films. Follow-up examinations including sequential BM biopsies (mean interval 39 +/- 31 months) disclosed that of the 43 patients with true ET only one developed an increase in reticulin. On the other hand, 65 of 77 patients with prefibrotic and early IMF evolved into overt myelofibrosis-osteosclerosis. Moreover, survival analysis demonstrated significant differences in our patients. A neglectable proportion of life loss according to a sex- and age-matched general population was found in true ET (less than 11%) opposed to IMF without or mild fibrosis (range 21% to 32%).
 ...
PMID:Follow-up examinations including sequential bone marrow biopsies in essential thrombocythemia (ET): a retrospective clinicopathological study of 120 patients. 1221 Aug 9

Angiogenesis has been implicated in the growth, dissemination and metastasis of solid tumours. Several recent studies have shown increased bone marrow vasculature in acute and chronic leukaemia as well as in myelofibrosis and myelodysplastic syndromes. Increased serum and/or cellular levels of vascular endothelial growth factor (VEGF) as the most potent and specific angiogenic factor were reported in acute and chronic leukaemia and multiple myeloma and also predict poor prognosis in these haematological malignancies. Little is known about angiogenesis and VEGF levels in polycythemia. Thus, the serum levels of VEGF (pg/ml) and erythropoietin (U/l) were determined using ultra-sensitive ELISA assays in 16 polycythemia patients (10 with polycythemia vera (PV) and 6 with secondary polycythemia) and correlated with their clinical and laboratory features. The serum levels of VEGF were significantly higher in 90% of PV cases and 60% of secondary polycythemia compared to healthy controls. The median VEGF levels (pg/ml) were 622 (range, 272-4760), 306 (range, 111-408) and 143 (range, 91-282) in PV, secondary polycythemia and healthy controls, respectively. Since serum VEGF reflects both plasma VEGF and platelet released VEGF, the concentration of VEGF per platelet (VEGF/PLT) as pg per 10(6) platelet was used as a more standardised measure. Splenomegaly emerged as the main factor associated with a marked increase in serum VEGF/PLT levels. On the other hand, the serum erythropoietin levels (U/l) were significantly reduced in PV (range, 1.2-14.3) raised in secondary polycythemia (range, 26-104) compared with normal controls (range, 9.7-31.1), P<0.01. In conclusion, the present study shows increased VEGF levels in most polycythemia patients, and splenomegaly is associated with a profound increase in VEGF serum levels in these patients. Also, patients with PV have significantly reduced serum levels of erythropoietin compared with secondary polycythemia. Also, serum VEGF/PLT was higher in PV patients treated with phlebotomy alone rather than oral chemotherapy, suggesting a possible advantage for chemotherapy over phlebotomy alone in suppressing the disease progression. Further studies with large number of polycythemia cases are warranted to explore the role of these cytokines in the pathogenesis, diagnosis and/or therapy of polycythemia.
 ...
PMID:Increased serum levels of vascular endothelial growth factor correlate with splenomegaly in polycythemia vera. 1236 69

Twenty-five patients with advanced essential thrombocythemia (ET; n = 13) or polycythemia vera (PV; n = 12) received hemopoietic stem cell transplants (HSCT) at the Fred Hutchinson Cancer Research Center. In most cases the indication to perform an HSCT was myelofibrosis with splenomegaly and peripheral blood cytopenias or the development of a myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Patients were 18-60 (median 43) years old with intervals from diagnosis to HSCT of 8-348 (median 168) months. All but five patients had been treated with cytotoxic agents, and nine patients were splenectomized before transplant. Conditioning was performed with chemotherapy only or chemotherapy plus total body irradiation regimens followed by the infusion of either marrow (n = 19) or peripheral blood stem cells (n = 6) from related (n = 16) or unrelated (n = 9) donors. All evaluable patients showed sustained neutrophil engraftment. Nine patients (seven with AML/MDS, two with myelofibrosis) died of transplant-related complications, and 16 are surviving, 14 of them in continuous unmaintained remission. With a median follow-up of 41 (range 5-116) months after transplant, survival at 3 years is 64%. These data provide evidence that HSCT can be a curative treatment for patients with advanced PV and ET.
 ...
PMID:Curative therapy of advanced essential thrombocythemia or polycythemia vera by hemopoietic stem cell transplantation. 1238 21


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>