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

Although hemolytic anemia and thrombosis, which can be serious or even lethal, are often encountered in daily common practice, their pathogenesis has remained obscure, partially because of the absence of appropriate models. Here we present a unique chemically induced rat model of hemolytic anemia and disseminated thrombosis in which the organs developing infarction are comparable to those seen in humans. We exposed male and female Fischer F344 rats to two, three, or four daily doses of 2-butoxyethanol (BE) at 250 mg/kg body weight and examined for hemolysis and histopathological evidence of disseminated thrombosis on d 2, 3, 4, and 29. Time-course BErelated erythrocytic changes were statistically significant in both sexes. Evidence of thrombosis and infarction was seen mainly in females dosed more than once with widespread thrombotic crisis after two or three dosing, likely explicable by the more significant morphological changes in erythrocytes and hemolysis observed in this gender. We documented thrombosis and infarction in the heart, brain, lungs, eyes, and bones. Our model with its list of target organs similar to that observed in human diseases characterized by hemolysis and thrombosis [for example, thalassemia, sickle cell disease (SCD), paroxysmal nocturnal hemoglobinuria (PNF), disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP), and hemolytic uremic syndrome (HUS)] suggests that it can be an excellent tool to study the pathogenesis of such complications.
Cardiovasc Toxicol 2002
PMID:A chemically induced rat model of hemolysis with disseminated thrombosis. 1266 64

The natural history of thalassemia has shown substantial change during these years. This applies for each aspect of the pathology (for example, endocrinological, hepatological and psychological) and also for the pathology that has presented and still presents the main cause of death: myocardial dysfunction. In this review, the pathophysiology of cardiac complications, possible role of myocarditis, new knowledge on pathogenesis, and noninvasive detection methods for iron overload in the heart are pointed out. Prophylaxis of cardiomyopathy and new therapy strategies of myocardial dysfunction, including the impact of the new chelation treatment, are discussed.
Expert Rev Cardiovasc Ther 2003 Sep
PMID:Cardiac complications in thalassemia: noninvasive detection methods and new directions in the clinical management. 1503 Feb 71

The past 3 years have been characterized by a number of impressive advances as well as setbacks in gene therapy for genetic disease. Children with X-linked severe combined immunodeficiency disorder (SCID-X1) have shown almost complete reconstitution of their immune system after receiving retrovirally transduced autologous CD34+ hematopoietic stem cells (HSCs). However, two of 11 treated patients subsequently developed a leukemia-like disease probablydue to the undesired activation of an oncogene. Gene transfer to HSCs resulted in substantial correction of immune function and multi-lineage engraftment in two patients with adenosine deaminase (ADA)-SCID. Several Phase I clinical trials for treatment of hemophilia A and B have been initiated or completed. Partial correction of hemophilia A, albeit transient, has been reported by ex vivo gene transfer to autologous fibroblasts. Intramuscular injection of adeno-associated viral (AAV) vector to patients with severe hemophilia B resulted in evidence of Factor IX gene transfer to skeletal muscle and a separate trial based on hepatic infusion of AAV vector is ongoing. Sustained therapeutic levels of coagulation factor expression have been achieved in preclinical models using retroviral, lentiviral, AAV and high capacity adenoviral vectors. Efficient lentiviral gene transfer to HSC in murine models of beta-thalassemia and sickle cell disease demonstrated sustained phenotypic correction.
Expert Rev Cardiovasc Ther 2003 Jul
PMID:Update on gene therapy for hereditary hematological disorders. 1503 Feb 82

In transfusion-dependent thalassemia major, iron-induced cardiomyopathy is the predominant cause of morbidity and mortality. Assessment of myocardial iron loading using MRI gradient echo T2* measurements have been described, but has only been performed at one centre in London. We assessed the transferability of this method by comparing the results from three different MR scanners in three different countries. Ten patients with thalassemia major underwent myocardial T2* assessment using a Siemens Sonata Scanner in London. Patients were also scanned with either a similar T2* sequence on a GE Systems CVI scanner in Athens, or a GE Systems signa echospeed scanner in Cagliari. Two scans were performed at the respective site in all patients to assess interstudy reproducibility at each site. The mean difference and coefficient of variability for the heart between scanners was 0.08 ms and 9.7% between London and Athens; and 0.30 ms and 1.6% between London and Cagliari. The interstudy mean difference and coefficient of variability for the heart in Athens was 0.6 ms and 3.5%, and 0.2 ms and 2.4% in Cagliari. In conclusion, the myocardial iron estimations were consistent between the three centres with scanners of differing manufacture, suggesting that this technique may have widespread application in the assessment of patients with iron overload conditions such as thalassaemia.
Int J Cardiovasc Imaging 2005 Oct
PMID:Intercentre reproducibility of magnetic resonance T2* measurements of myocardial iron in thalassaemia. 1617 43

Bone marrow transplantation (BMT) is the only complete cure for b-thalassemia. Iron depletion therapy is still required to remove excess iron, accumulated before BMT. Hepatic and myocardial iron load were evaluated using T2* magnetic resonance in 8 ex-thalassemic patients after BMT, aged 19.5 +/- 4.25 years, who were in iron depletion therapy. Average hepatic T2* was 18.8 +/- 11.0 msec (4.1-35.0 msec). In 4 out of 8 patients iron overload was detected, not exceeding however 4 mg/gr dry tissue. Average heart T2* was 31.0 +/- 4.6 msec (25.6-35.2 msec), not significantly different (P = 0.18) from our age-matched normal population (33.0 +/- 4.0). Normal left ventricular ejection fraction was found in 7 out of 8 patients (mean 64.5 +/- 7.0%) with the remaining having a marginal value of 54.1%. Ferritin level before BMT was 1748 +/- 451 mug/l and dropped to 536 +/- 260 microg/l at the end of iron depletion therapy after BMT. Current ferritin level was 271 +/- 253 microg/l and although it was significant lower compared to both ferritin before BMT (P < 0.001) and after iron depletion (P < 0.001), evidence of residual hepatic iron load was identified by T2*. Hepatic and myocardial T2* magnetic resonance can be used as a more reliable index than ferritin for evaluation of iron depletion therapy in ex-thalassemic patients after BMT.
Int J Cardiovasc Imaging 2007 Dec
PMID:Myocardial and hepatic T2* magnetic resonance evaluation in ex-thalassemic patients after bone-marrow transplantation. 1723 81

Thalassemia major is an inherited hemoglobin disorder resulting in a chronic hemolytic anemia. Transfusion therapy together with elevated gastrointestinal absorption of iron determines iron overload, which causes most of the mortality and morbidity associated with the disease. Heart complications represent the leading cause of mortality in this disease, although, because of an improvement in chelation treatment, an important and progressive increase of life expectancy mainly as a result of a reduction in mortality due to cardiac dysfunction has been demonstrated in recent years. Clinical pictures of heart damage range from the involvement of the ventricles to pulmonary hypertension or symptomatic ventricular or supra-ventricular arrhythmias. For this reason, the possibility of having specific recommendations is noteworthy. These recommendations outline the definition, the follow-up and the treatment of the main heart complications in this group of patients. The identification of topics and the nomination of the committee were made on behalf of the Society for the Study of Thalassemia and Hemoglobinopathies (SoSTE). The document obtained the auspices of ANMCO, SIC, SIRM and the Cardiovascular Magnetic Resonance Working Groups of the ANMCO, SIC and SIRM. All recommendations provided in this document have been performed according to the American Cardiology College (ACC) and American Heart Association (AHA) guidelines. Moreover, the recommendations were reviewed by two external referees before the definitive approval.
J Cardiovasc Med (Hagerstown) 2008 May
PMID:Guideline recommendations for heart complications in thalassemia major. 1840 6

To evaluate left and right ventricular myocardial performance using pulsed-tissue Doppler imaging (TDI) and its relation to BNP levels in patients with beta-thalassaemia major (beta-TM). We enrolled 36 thalassaemic patients (21 male, 15 female; mean age: 14.2 +/- 4.1 years) with normal left ventricular systolic and diastolic functions with conventional echocardiography and 30 healthy control subjects (18 male, 12 female, and 12.5 +/- 4.2 years). Myocardial performance indexes (MPI) of left ventricular (LV) lateral wall, interventricular septum (IVS) and right ventricular (RV) lateral wall were calculated with TDI. Plasma BNP levels were measured in all patients. MPIs and other echocardiographic parameters of patients with beta-TM were compared with control group. All the patients' plasma BNP levels were within normal limits. There were no differences between conventional echocardiographic parameters of patients and control group. MPI of LV, IVS, and RV of patients were significantly higher than control group (P = 0.01, and P < 0.01, and P < 0.001, respectively). Our study confirms that MPI obtained by TDI seems to be an early sensitive parameter of cardiac dysfunction in beta-TM. We concluded that MPI obtained by TDI may be an adjunctive parameter to conventional echocardiography for detecting early myocardial damage.
Int J Cardiovasc Imaging 2009 Apr
PMID:Early detection of myocardial dysfunction in children with beta-thalassaemia major. 1910 72

Data concerning electrocardiographic (ECG) abnormalities in thalassemic cardiomyopathy are scanty. Current techniques to detect early findings of myocardial involvement in thalassemia (Magnetic Resonance, Stress Echo, Tissue Doppler Imaging) are not widely available. We sought to determine whether new ECG abnormalities emerge in thalassemia patients when heart failure due to cardiomyopathy occurs. ECG and Echo Doppler examinations of 28 consecutive adult thalassemia patients with heart failure observed at our hospital were compared with ECG and Echo Doppler examinations performed before the onset of heart dysfunction and with those of 60 age and sex-matched patients with thalassemia without evidence of cardiac involvement. All the patients with heart failure had new ECG abnormalities. New onset supraventricular arrhythmias, T wave inversion, low voltages, right QRS axis deviation and S1Q3 pattern developed respectively in 46%, 79%, 43%, 18% and 15% of thalassemic patients with heart failure. None of the patients without heart failure showed any ECG abnormality (P<0.001). In conclusion this study suggests that new onset ECG abnormalities are always evident in patients with and always absent in patients without heart failure due to thalassemic cardiomyopathy.
Cardiovasc Hematol Disord Drug Targets 2009 Mar
PMID:Electrocardiographic abnormalities in thalassemia patients with heart failure. 1927 75

Thalassaemia is a serious inherited disorder with a high prevalence in south-east Asian countries, including Thailand. Several complications of thalassaemia have been documented. Infection is a major problem and the leading cause of death, particularly in E-beta thalassaemia.
Cardiovasc J Afr
PMID:Rheumatic valvular heart disease in thalassaemic patients: a summary of reported Thai cases. 1957 89

In b-thalassemia, myocardial iron overload contributes to heart failure, despite chelation treatment. We hypothesized that myocardial T2*, an index of iron overload, influences patients' physical activity. We assessed a thalassemic population by both cardiovascular magnetic resonance imaging (CMR) and ergospirometry test. Sixty-six thalassemic patients aged 27 (19-40) years, 30 without (NHF) and 36 with heart failure (HF), were studied. Cardiac T2* and left ventricular ejection fraction (LVEF) were evaluated using a 1.5 T system. VO(2max), AT, Mets and duration of exercise by ergospirometry were also assessed. Myocardial T2* was lower in HF compared to NHF patients (14.7 +/- 6.6 vs. 39 +/- 2 ms, P < 0.001). LVEDV and LVESV were higher in HF group compared to NHF patients (139.9 +/- 16.3 vs. 124.6 +/- 20.86 ml, P < 0.01 and 94.9 +/- 24 vs. 38.3 +/- 10.1 ml, P < 0.001, respectively). Additionally, LVEF in HF was lower compared to NHF patients (21.3 +/- 6.1% vs. 69.6 +/- 3.7, P < 0.001, respectively). All exercise parameters were lower in HF compared to NHF patients (P < 0.001). Patients within the HF group were additionally analyzed according to T2* values (<10 ms). HF patients with T2* < 10 ms (n = 13) were considered as high iron overloaded (HF-H) and the rest of them (n = 23) as (HF-L). Although LVEDV, LVESV, LVEF were similar in the two subgroups, the exercise parameters were significantly lower in the HF-H group (P < 0.001). Heart T2* correlated with all exercise parameters (P < 0.001). HF thalassemic patients have reduced exercise indexes compared to non HF. Myocardial iron overload, expressed as T2*, has a direct influence on exercise capacity, independent of LV ejection fraction and functional class.
Int J Cardiovasc Imaging 2009 Dec
PMID:Effect of iron overload on exercise capacity in thalassemic patients with heart failure. 1993 25


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