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)

Generalized epileptiform seizures developed in a 23-year-old patient with beta-thalassemia-hemoglobin E. A computed tomographic scan suggested an intracranial mass. Surgery disclosed an extramedullary hematopoietic mass compressing the brain. Removal of the mass followed by irradiation of the area resulted in disappearance of the convulsions.
 ...
PMID:Intracranial extramedullary hematopoiesis inducing epilepsy in a patient with beta-thalassemia--hemoglobin E. 398 37

Cyclosporin A (CsA) has been shown to be useful in the prophylaxis of acute graft-versus-host-disease (GVHD). However, this immunosuppressive agent produces multiple side-effects including nephrotoxicity, hypertension, hypertricosis, gum hyperplasia, infections, and neurotoxicity. We report a retrospective analysis of neurotoxicity in 625 recipients transplanted for thalassemia and given CsA as part of GVHD prophylaxis. Neurotoxicity consisted in mental status changes, tremor, headache (grade 1), visual disturbance and cortical blindness (grade 2) and seizures and coma (grade 3). The overall toxicity was 28.8% and the incidence of convulsions was 10.1%. Neurological findings were reversible after temporary reduction or discontinuation of CsA. Class 3 patients, when prepared with protocol 6 (Bu 14 + Cy 200 and CsA for GVHD) or when they developed acute GVHD, had the highest risk of convulsions. Age, sex, different conditioning regimens, different anticonvulsive prophylaxis, liver damage due to iron-overload and/or to chronic inflammation did not influence the occurrence of CsA-related CNS toxicity. The occurrence of acute GVHD with concomitant use of high-dose corticosteroids is the single significant predisposing factor in the occurrence of convulsions. Grades 1 and 2 of neurotoxicity occurred earlier and were not influenced even by acute GVHD.
 ...
PMID:CsA-associated neurotoxicity and ineffective prophylaxis with clonazepam in patients transplanted for thalassemia major: analysis of risk factors. 883 9

We analyzed plasma pharmacokinetics of busulfan in 64 children and young adults (age 2.8-26; median 11 years) with homozygous beta-thalassemia transplanted with bone marrow from HLA-identical sibling donors. A uniform conditioning regimen was employed, using busulfan 14 or 16 mg/kg in 12 divided doses, and cyclophosphamide 120 or 200 mg/kg. Three sets of parameters were examined in this homogenous patient population: (1) factors that affect the plasma kinetics of busulfan, such as age and pre-transplant liver status defined by liver function tests, ferritin levels and liver biopsy; (2) busulfan-related toxicity: occurrence of veno-occlusive disease, seizures and idiopathic interstitial pneumonitis; and (3) the relationship between busulfan exposure and transplant outcome: engraftment delay or rejection, aplasia, occurrence of mixed chimeras and mortality. Kinetic analysis of first and 10th dose (using area under the curve (AUC), maximum and minimum concentration) as comparable, showing no sign of accumulation or decline in busulfan plasma levels over time. Age and liver status did not influence busulfan metabolism. No relationship was found between busulfan exposure and toxicities or transplant outcome. We conclude that busulfan monitoring is not predictive in children and young adults with homozygous beta-thalassemia receiving busulfan and high-dose cyclophosphamide along with histocompatable sibling donor marrow.
 ...
PMID:Relationship of plasma pharmacokinetics of high-dose oral busulfan to the outcome of allogeneic bone marrow transplantation in children with thalassemia. 942 69

Thromboembolic (TE) events have been frequently reported in beta-thalassemic patients in association with known risk factors such as diabetes, complex cardiopulmonary abnormalities, hypothyroidism, liver function anomalies, and postsplenectomy thrombocytosis. In a recent survey involving 9 Italian thalassemic centers, we identified 32 patients with TE episodes in a total of 735 subjects, of whom 683 had thalassemia major and 52 thalassemia intermedia, corresponding to 3.95 and 9.61%, respectively. There was a great variation in localization: the main one (16/32) was CNS, with a clinical picture of headache, seizures and hemiparesis. Other localizations were the pulmonary (3 patients), mesenteric (1 patient) and portal (2 patients) sites. There were 6 cases of deep venous thrombosis (2 in the upper limbs, 4 in the lower ones). Intracardiac thrombosis was found in 2 subjects and clinical and laboratory signs of DIC were observed in 2 others during pregnancy. Since our patients with TE events present a statistically significantly higher incidence of associated dysfunction (cardiomyopathy, diabetes, liver function anomalies, hypothyroidism) than those without TE events (50 vs. 13.8%), we suggest close monitoring of those patients who are at higher risk of developing TE events because of the presence of one or more of these predisposing factors.
 ...
PMID:Thromboembolic events in beta thalassemia major: an Italian multicenter study. 985 99

Several X-linked mental retardation syndromes are caused by mutations in the ATRX gene. Common clinical features associated with ATRX mutations include severe mental retardation, characteristic facial anomalies and variable degrees of urogenital defects and alpha-thalassemia. Although the ATRX protein is a member of the SWI/SNF family of chromatin remodeling proteins, little is known about the biochemical activity of the ATRX protein or its in vivo function during development. Here we demonstrate that ATRX is part of a large multiprotein complex similar in size to the SWI/SNF complex. Furthermore, we have generated transgenic mice that overexpress ATRX as an initial model for studying the function of this protein during development. Misexpression of ATRX was associated with growth retardation, neural tube defects and a high incidence of embryonic death. Moreover, brains from E10.5 transgenic embryos displayed abnormal growth and organization of the ventricular zone that was highly convoluted in the most severely affected embryos. Transgenic mice that survived to birth exhibited a high incidence of perinatal death, as well as seizures, mild craniofacial anomalies and abnormal behavior. Our findings indicate that ATRX dosage is crucial for normal development and organization of the cortex, and emphasize the relevance of our model for the study of ATRX function and disease pathogenesis.
 ...
PMID:Neurodevelopmental defects resulting from ATRX overexpression in transgenic mice. 1182 44

Cyclosporin A is an essential drug for graft versus host disease (GvHD) prophylaxis in allogeneic hematopoietic stem cell transplantation. Cyclosporin A-associated neurotoxicity is common but poorly understood. The authors herein report on 3 patients receiving transplants for thalassemia. GvHD prophylaxis included cyclosporin A, prednisolone, and methotrexate. All patients developed a status epilepticus with cortical signal alterations located mainly in occipital regions on T2-weighted magnetic resonance imaging. Complete disappearance of the neurologic symptoms and radiographic findings was observed without discontinuing cyclosporin A therapy. Especially, pediatric thalassemics receiving busulfan/cyclophosphamide as preparative regimen seem to be significantly prone to cyclosporin A-associated seizures.
 ...
PMID:Cyclosporin A-associated status epilepticus related to hematopoietic stem cell transplantation for thalassemia. 1463 24

Twenty-one children and young adults with sickle/beta-thalassemia without overt stroke were examined with magnetic resonance imaging and angiography (MRA), transcranial Doppler (TCD), visual (VEP) and median nerve somatosensory (SEP)-evoked potential recordings, and neuropsychological testing (Wechsler Intelligence Scale [WISC-III]). Eight (38%) had silent infarction in the parietooccipital cortex, deep white matter, or basal ganglia, including two of three with previous seizures. Of 17 undergoing TCD, none had maximum middle cerebral artery (MCA) velocities greater than 126cm/sec, but 9 were abnormal, with low velocities and difficulty in tracking the MCA and/or asymmetry. Three patients had abnormal MRA, one of whom also had silent infarction. One patient had pathological VEP recordings, whereas all SEP recordings were normal. WISC-III was performed in all 11 children, 4 with silent infarction: all but 1 had IQ scores greater than 85 (mean, 97.7; standard deviation, 14.2). We conclude that Greek children and young adults with Sbeta-thalassemia and no history of clinical stroke have TCD abnormalities and silent infarction similar to those reported in children and adolescents with sickle cell anemia, but cognitive function is not necessarily compromised. International collaboration is needed to establish the risk factors for central nervous system sequelae in patients with sickle cell disease, including Sbeta-thalassemia, leading to evidence-based prevention.
 ...
PMID:Central nervous system abnormalities in asymptomatic young patients with Sbeta-thalassemia. 1517 17

Neuroimaging and management advances require review of indications for excluding cerebral venous sinus (sinovenous) thrombosis (CSVT) in children. Our goals were to examine (i) clinical presentations of CSVT, (ii) prothrombotic risk factors and other predisposing events, (iii) clinical and radiological features of brain lesions in CSVT compared with arterial stroke, and (iv) predictors of outcome. We studied 42 children with CSVT from five European paediatric neurology stroke registries. Patients aged from 3 weeks to 13 (median 5.75) years (27 boys; 64%) presented with lethargy, anorexia, headache, vomiting, seizures, focal signs or coma and with CSVT on neuroimaging. Seventeen had prior chronic conditions; of the 25 previously well patients, 23 had recent infections, eight became dehydrated and six had both. Two children had a history compatible with prior CSVT. Anaemia and/or microcytosis (21 probable iron deficiency, five haemolytic, including two with sickle cell disease and one with beta-thalassaemia) was as common (62%) as prothrombotic disorder (13/21 screened). High factor VIII and homozygosity for the thermolabile methylene tetrahydrofolate reductase polymorphism were the commonest prothrombotic disorders. The superficial venous system was involved in 32 patients, the deep in six, and both in four. Data on the 13 children with bland infarction and the 12 with haemorrhage in the context of CSVT were compared with those from 88 children with ischaemic (AIS) and 24 with haemorrhagic (AHS) arterial stroke. In multiple logistic regression, iron deficiency, parietal infarction and lack of caudate involvement independently predicted CSVT rather than arterial disease. Five patients died, three acutely, one after recurrence and one after 6 months being quadriparetic and blind. Follow-up ranged from 0.5 to 10 (median 1) years. Twenty-six patients (62%) had sequelae: pseudotumour cerebri in 12 and cognitive and/or behavioural disabilities in 14, associated with epilepsy in three, hemiparesis in two and visual problems in two. Eighteen patients, including six with haemorrhage, were anticoagulated. Older age [odds ratio (OR) 1.54, 95% confidence limits (CI) 1.12, 2.13, P = 0.008], lack of parenchymal abnormality (OR 0.17, 95% CI 0.02, 1.56, P = 0.1), anticoagulation (OR 24.2, 95% CI 1.96, 299) and lateral and/or sigmoid sinus involvement (OR 16.2, 95% CI 1.62, 161, P = 0.02) were independent predictors of good cognitive outcome, although the last predicted pseudotumour cerebri. Death was associated with coma at presentation. Of 19 patients with follow-up magnetic resonance (MR) venography, three had persistent occlusion, associated with anaemia and longer prodrome. A low threshold for CT or MR venography in children with acute neurological symptoms is essential. Nutritional deficiencies may be modifiable risk factors. A paediatric anticoagulation trial may be required, after the natural history has been further established from registries of cases with and without treatment.
 ...
PMID:Cerebral venous sinus thrombosis in children: risk factors, presentation, diagnosis and outcome. 1569 61

Systemic disease, either genetic or acquired, may prevent or decrease the severity of another disease. These observations have led to important therapeutic advances. The best-known examples are Edward Jenner's use in 1798 of cowpox to prevent smallpox and J.B. Haldane's 1942 observation that erythrocyte disorders such as thalassemia and sickle cell disease modify the severity of malaria. Patients with and carriers of cystic fibrosis may have genetic resistance to tuberculosis and/or secretory diarrhea. The beneficial effects of undernutrition have led to therapeutic diets for seizures, celiac disease, type 2 diabetes, and inflammatory bowel disease. Finasteride for prostatic hypertrophy was developed after the observation that patients with male pseudohermaphrodism resulting from 5-alpha-reductase mutations do not develop prostatic hypertrophy. Rh immunoglobulin for Rh hemolytic disease prevention followed the observation that ABO incompatibility prevented Rh sensitization. The natural immunosuppression of measles may cause remission of nephrosis, and that of leprosy prevents psoriasis. Patients with one form of agammaglobulinemia (X-linked) never get Epstein-Barr virus infection, and patients with another form (common variable) are seemingly cured by HIV infection. HIV/AIDS is prevented or modified by co-receptor mutations (notably the CCRDelta32 chemokine mutation), HIV-2, or GB virus C infection. Additional exploration of these genetic, infectious, and metabolic influences on disease severity may provide new therapeutic approaches to HIV and other diseases.
 ...
PMID:Disease versus disease: how one disease may ameliorate another. 1639 76

Pharmacological induction of hemoglobin F expression may be a promising approach for the treatment of beta-thalassemia and sickle cell disease. Valproic acid, a drug frequently used for the treatment of seizure disorders, has been shown to enhance fetal hemoglobin synthesis in erythroid cells. However, this effect is only modest and requires relative high concentrations. Therefore, the drug appears not to be applicable for the treatment of beta-globin chain disorders. Here, we describe the identification of novel valproic acid derivatives with potent hemoglobin F inducing activities at concentrations that presumably can be obtained in vivo.
 ...
PMID:Novel valproic acid derivatives with hemoglobin F inducing activity. 1662 26


1 2 3 Next >>