Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Measurement of liver iron concentration (LIC) is necessary for a range of iron-loading disorders such as hereditary hemochromatosis, thalassemia, sickle cell disease, aplastic anemia, and myelodysplasia. Currently, chemical analysis of needle biopsy specimens is the most common accepted method of measurement. This study presents a readily available noninvasive method of measuring and imaging LICs in vivo using clinical 1.5-T magnetic resonance imaging units. Mean liver proton transverse relaxation rates (R2) were measured for 105 humans. A value for the LIC for each subject was obtained by chemical assay of a needle biopsy specimen. High degrees of sensitivity and specificity of R2 to biopsy LICs were found at the clinically significant LIC thresholds of 1.8, 3.2, 7.0, and 15.0 mg Fe/g dry tissue. A calibration curve relating liver R2 to LIC has been deduced from the data covering the range of LICs from 0.3 to 42.7 mg Fe/g dry tissue. Proton transverse relaxation rates in aqueous paramagnetic solutions were also measured on each magnetic resonance imaging unit to ensure instrument-independent results. Measurements of proton transverse relaxivity of aqueous MnCl2 phantoms on 13 different magnetic resonance imaging units using the method yielded a coefficient of variation of 2.1%.
 ...
PMID:Noninvasive measurement and imaging of liver iron concentrations using proton magnetic resonance. 1525 27

Human pythiosis is an emerging disease in the tropical, subtropical and temperate regions of the world. It is caused by the straminipilan, fungus-like, aquatic organism Pythium insidiosum. Pythiosis occurs in localized as well as systemic or vascular forms. Most patients with arterial pythiosis usually have underlying hematologic disorders such as thalassemia and aplastic anemia/paroxysmal nocturnal hemoglobinuria (PNH) syndrome. Vascular pythiosis is characterized by ascending blood vessel infections and thrombosis of the major arteries especially those of the lower extremities. When the infection reaches a main artery, the patient usually dies within weeks. Since this pathogen is resistant to most antifungal drugs, immunotherapy was recently used to cure humans and animals with the disease. A modified P. insidiosum-antigen (PIA) formulation had already saved a young boy with life-threatening arterial pythiosis. Here, we report the therapeutic benefits of the PIA in eight patients with vascular pythiosis. Six of them had thalassemia and the other two had PNH. All of the patients had arterial occlusion of the lower limbs. P. insidiosum was isolated and identified by culture and by histopathology. All patients had evidence of active infection when immunotherapy began. After two injections of 100-200 microl of PIA (2.0mg/ml), at a 14-day interval, four patients (50%) had dramatic and complete remission. Two patients showed partial responses to PIA while the other two did not. Clinical responses correlated with the immunological reactions at the site of injection, clearance of the arteries and cytokine production. The latter included the shifting in serum levels of IL4 and IL5 to IL2 suggesting a switching from a T helper 2 (Th2) to a T helper 1 (Th1) subset. Our findings provide further evidence that immunotherapy using PIA is a safe and effective method to treat pythiosis in humans.
 ...
PMID:Efficacy of immunotherapy using antigens of Pythium insidiosum in the treatment of vascular pythiosis in humans. 1531 40

Increased rates of graft rejection after bone marrow transplantation (BMT) are observed in patients whose illnesses--such as sickle cell disease, thalassemia, and aplastic anemia--necessitate chronic transfusion before BMT. Because BM transplants in these patients are routinely HLA matched, any immunization responsible for increased rejection is likely against minor histocompatibility antigens (mHAs). It has been assumed that contaminating leukocytes in red blood cell (RBC) units are the main sources of immunization to mHAs. However, in this report, we demonstrate that antigens on donor RBCs are presented in the major histocompatibility complex (MHC) class I pathway of recipient antigen-presenting cells, resulting in activation and expansion of recipient CD8+ T cells specific for donor mHAs. Given that human hematopoietic progenitor cells express many of the known mHAs, this observation provides a mechanism by which chronic transfusion of even stringently leukoreduced RBCs may result in sufficient mHA immunization to increase the frequency of BMT rejection.
 ...
PMID:Immunization to minor histocompatibility antigens on transfused RBCs through crosspriming into recipient MHC class I pathways. 1612 13

Allogeneic stem cell transplantation (HSCT) requires the harvest of an adequate number of stem cells (SC) from a histocompatible donor and their infusion into a patient following a conditioning regimen. During the past 35 years, the role of HSCT has changed from an experimental procedure for terminally ill patients to a curative treatment. In 2003, 1170 procedures were registered in Italy (Italian Group for Blood and Marrow Transplantation). The main reported indications were as follows: leukemia, lymphoproliferative diseases, myelodysplasia, and nonmalignant diseases such as thalassemia and severe aplastic anemia. Important changes have been observed in the last 5 years: the shift from bone marrow to peripheral blood as the SC source, the increasing number of alternative donors such as unrelated, partially matched family donors and cord blood SC, and the new extra-hematological indications including solid tumors. Moreover, the development of nonmyeloablative conditioning regimens have allowed physicians to perform HSCT in patients with advanced age or important comorbidities. In contrast, the availability of the Tyrosine kinase inhibitor (STI-571) for treatment of patients affected by chronic myelogenous leukemia, which was formerly the main indication for HSCT, has produced a dramatic decrease in the number of transplantations in this setting. HSCT performed in the early phases of disease and in young patients offers more than a 50% cure rate. The transplant-related mortality still represents the greatest obstacle, ranging from 20%-30%, despite the less toxic conditioning regimens, high-resolution HLA typing, and better supportive care. GvHD and infections remain the main causes of morbidity. As regards relapses, they correlate with disease status at the time of transplantation. Promising results have been recently obtained with haploidentical and with cord blood SC transplantation also in adult patients.
 ...
PMID:Allogeneic stem cell transplantation. 1618 79

We analyzed the records of 153 Guadeloupean children with sickle cell anemia (SCA), for whom clinical and laboratory data were prospectively collected (mean follow-up duration 8.4 +/- 4.6 yr). Prevalence and age-specific frequencies of acute clinical events were determined and correlations between complications, hematological parameters and potential modulating factors investigated. Painful crisis and acute chest syndrome (ACS) were the two most common complications, affecting 65.4% and 58.8% of the patients, respectively. The frequency of acute anemia was 49.7% (acute splenic sequestration 24.8%; acute aplastic anemia 15.0%). Prevalences of septicemia-meningitis and osteomyelitis were 15.7% and 16.3%, respectively. A higher incidence of infections, painful crises and acute anemia was detected in patients who developed ACS. The well-documented protective effect of HbF level on the overall disease expression was observed with higher HbF level in asymptomatic than in symptomatic patients (17.5% +/- 8% vs. 9.9% +/- 6.4%, P = 0.01) with similar ages and sex ratio. It was also confirmed on ACS and, for the first time, further extended to acute anemic events and septicemia. Besides its effect on hematological parameters, alpha-thalassemia seems to have little impact on the prevalence of complications, as do beta(S)-globin haplotypes. Comparison with other series suggests that the natural history of SCA in Guadeloupe is more similar to that in Jamaica with regard to those reported in Europe and the United States, suggesting a potential impact of environmental factors on the clinical course of the disease.
 ...
PMID:Sickle cell anemia in Guadeloupean children: pattern and prevalence of acute clinical events. 1645 94

Hypocholesterolemia of unknown etiology has been previously described in various chronic anemias. Few small studies also suggested that those patients have a lower incidence of atherosclerotic events. The aim of our study was to determine the extent of hypocholesterolemia in various types of anemias. We studied 59 patients with chronic anemias associated with high-erythropoietic activity (thalassemia intermedia, congenital dyserythropoietic anemia type I, congenital spherocytosis), 8 patients with low-erythropoietic activity anemias (acquired aplastic anemia, Fanconi anemia, and Diamond Blackfan anemia), and 20 healthy controls. Mean serum cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, hemoglobin, serum ferritin, soluble transferrin receptor (STR), and serum erythropoietin levels were determined in each patient. All patients with chronic anemia and increased erythropoietic activity had hypocholesterolemia, whereas none of those with low erythropoietic activity was hypocholesterolemic. Mean serum cholesterol, HDL cholesterol, and LDL cholesterol levels were found to be significantly lower in the high-erythropoietic activity group (80+/-19 mg/dl; 31+/-10 mg/dl; 35+/-14 mg/dl, respectively) compared with the control group (P<0.001; 0.001; 0.001, respectively) and the low-erythropoietic activity group (P<0.001; 0.001; 0.01, respectively). Significant inverse correlation (R2=0.507) was observed between serum cholesterol and STR levels, which in the absence of iron deficiency reflect bone marrow activity. Taken together, our results imply that hypocholesterolemia accompanies anemias with high-erythropoietic activity. We suggest that the high-erythropoitic activity-associated hypocholesterolemia is due to increased cholesterol requirements by the proliferating erythoid cells. Further studies are needed to elucidate the exact mechanism and the possible clinical consequences of this phenomenon.
 ...
PMID:Hypocholesterolemia in chronic anemias with increased erythropoietic activity. 1703 15

Haematopoietic stem cell transplantation (HSCT) is now an established treatment fora number of non-malignant and malignant conditions. Bone marrow- or peripheral blood-derived allogeneic SCT from an HLA-identical sibling or matched unrelated donor cures more than half the patients with severe aplastic anaemia, thalassaemia major, congenital immunodeficiency diseases and genetic metabolic disorders. Among the malignant conditions, acute and chronic leukaemia, multiple myeloma, Hodgkin and non-Hodgkin lymphoma, and high risk neuroblastoma are important conditions that can be treated by HSCT. The major morbidities associated with HSCT are regimen-related toxicities, development of acute or chronic graft-versus-host disease (GVHD), failure of engraftment of the bone marrow and complications related to the immunodeficiency that occurs in the post-transplant period. Peripheral blood stem cells are now being used as an alternative to bone marrow stem cells for allogeneic HSCT and exclusively for autologous HSCT. Reduced intensity conditioning for allogeneic HSCT has resulted in a lower frequency and severity of GVHD and risk of infections. This has resulted in allogeneic HSCT being done in older patients and for those with co-morbid conditions. Patients with low grade Hodgkin and non-Hodgkin lymphoma, chronic lymphocytic leukaemia and multiple myeloma appear to benefit more with this approach. Prevention of acute GVHD while maintainingthe graft-versus-tumour effect and close monitoring of the kinetics of chimerism hold promise for improving the outcome of those receiving reduced intensity allogeneic HSCT. In recipients ofautologous HSCT, identification of patients at increased risk for relapse and use of agents (interferon, interleukin-2) post-transplant to augment the graft-versus-tumour effect are possible areas of further research.
 ...
PMID:Haematopoietic stem cell transplantation: current status. 1786 17

Anemia can result from deficient erythropoiesis [aplastic anemia, myelodysplastic syndromes (MDS), iron deficiency anemia, anemia of chronic disease (ACD), thalassemia, megaloblastic anemia, chronic renal failure, hematological malignancies, etc.], excessive RBC destruction [hereditary spherocytosis, inherited enzyme deficiency, hemoglobinopathies, autoimmune hemolytic anemia (AIHA), paroxysmal nocturnal hemoglobinuria (PNH), etc.], and blood loss. Based on the measured red cell size(MCV), anemia is classified as microcytic, normocytic, or macrocytic. Iron parameters (serum iron, serum ferritin, etc.), reticulocyte count, bone marrow examination, Coombs test, serum vitamin B12 level, and Ham test are also useful in the differential diagnosis of anemia. Novel treatment of anemia includes lenalidomide for 5q(-)MDS, azacitidine for high-risk MDS, and eculizumab for PNH. Oral iron chelator(deferasirox) developed for the treatment of transfusional iron overload is also very useful for the management of patients with bone marrow failure syndromes.
 ...
PMID:[Pathophysiology, diagnosis and treatment of anemia]. 1832 12

The pharmacokinetics (PK) and pharmacodynamics (PD) of the once-daily, oral ironchelating agent, deferasirox (Exjade, ICL670), have been evaluated further in a Phase I, openlabel, multicenter, dose-escalation study in Japanese patients with myelodysplastic syndromes, aplastic anemia, and other anemias. Deferasirox was initially administered as a single dose of 5 (n = 6), 10 (n = 7), 20 (n = 6) or 30 (n = 7) mg/(kg day) and then after 7 days seven daily doses were administered. Linear PK (C (max) and AUC) were observed at all doses after a single dose and at steady state, and dose-dependent iron excretion was observed. Pharmacokinetic/pharmacodynamic parameters were similar to those reported in a Caucasian beta-thalassemia cohort. Following the single- and multiple-dose phases, 21 of 26 patients progressed to a 3-year extension phase of the study, where dose reductions and increases [5-30 mg/(kg day)] were allowed following safety and efficacy assessments. In the interim, 1-year data show that deferasirox was well tolerated, with generally infrequent and mild adverse events. Reductions in serum ferritin levels were observed and a negative iron balance achieved at doses of 20-30 mg/(kg day). These data suggest that deferasirox has a stable and predictable PK/PD profile, irrespective of underlying disease or race, and a predictable and manageable safety profile suitable for chronic administration.
 ...
PMID:A safety, pharmacokinetic and pharmacodynamic investigation of deferasirox (Exjade, ICL670) in patients with transfusion-dependent anemias and iron-overload: a Phase I study in Japan. 1859 54

From March 1991 through 31st December 2007, 2042 patients underwent stem cell transplantation at the Hematology-Oncology and Stem Cell Transplantation Research Center, affiliated to Tehran University of Medical Sciences. These transplantations included 1405 allogeneic stem cell transplantation, 624 autologous stem cell transplantation, and 13 syngeneic stem cell transplantation. Stem cell transplantation was performed for various diseases including acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, chronic lymphoblastic leukemia, thalassemia major, sickle cell thalassemia, sickle cell disease, multiple myeloma, myelodysplasia, mucopolysaccharidosis, paroxysmal nocturnal hemoglobinuria, non-Hodgkin's lymphoma, Hodgkin's disease, severe aplastic anemia, plasma cell leukemia, Niemann-Pick disease, Fanconi anemia, severe combine immunodeficiency, congenital neutropenia, leukocyte adhesion deficiencies, Chediak-Higashi syndrome, osteopetrosis, histiocytosis X, Hurler syndrome, amyloidosis, systemic sclerosis, breast cancer, Ewing's sarcoma, testicular cancer, germ cell tumors, neuroblastoma, medulloblastoma, renal cell carcinoma, nasopharyngeal carcinoma, ovarian cancer, Wilms' tumor, rhabdomyosarcoma, pancreatoblastoma, and multiple sclerosis. We had 105 cellular therapies for postmyocardial infarction, multiple sclerosis, cirrhosis, head of femur necrosis, and renal cell carcinoma. About 30 patients were retransplanted in this center. About 74.9% of the patients (1530 of 2042) remained alive between one to 168 months after stem cell transplantation. Nearly 25.1% (512 of 2042) of our patients died after stem cell transplantation. The causes of deaths were relapse, infections, hemorrhagic cystitis, graft versus host disease, and others.
 ...
PMID:Stem cell transplantation; Iranian experience. 1911 Oct 33


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