RESUMEN
Primary immune thrombocytopenia (ITP) is the commonest acquired cause of bleeding in childhood. The aim of the present study was to evaluate the role of FcγRIIa and FcγRIIIa polymorphisms in the pathogenesis and therapeutic result of childhood ITP. The genotypic frequencies for two Fcγ receptor single-nucleotide polymorphisms, FcγRIIa-131 arginine (R) versus histidine (H) and FcγRIIIa-158 valine (V) versus phenylalanine (F) were examined in 53 children diagnosed with ITP. The genotype frequencies were compared with those of 45 healthy controls. The association between the above frequencies and disease natural course as well as therapeutic result following intravenous immunoglobulin (IVIG) administration was investigated. FcγRIIIa-158V was significantly overrepresented in children with ITP versus controls (P = 0.029), whereas no statistically significant difference was noted in FcγRIIa polymorphism distribution. No statistically significant difference was noted in the above genotype frequencies' distribution between children with newly diagnosed and chronic ITP, as well as with regards to the therapeutic result following IVIG administration. High-affinity FcγRIIIa variant (158 V) is possibly implicated in disease susceptibility, but neither of the two Fcγ receptor single-nucleotide polymorphisms seem to have any impact on chronicity or therapeutic effect of IVIG.
Asunto(s)
Polimorfismo de Nucleótido Simple , Púrpura Trombocitopénica Idiopática/genética , Receptores de IgG/genética , Adolescente , Alelos , Niño , Preescolar , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Grecia , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Lactante , Masculino , Púrpura Trombocitopénica Idiopática/terapia , Receptores de IgG/fisiología , Resultado del TratamientoRESUMEN
Beta thalassemia is known to be characterized by a hypercoagulable state, with prothrombotic factors present and thrombotic event development in a number of patients. The aim of the present study was to evaluate subclinical involvement of the central nervous system (CNS) in young patients with thalassemia intermedia, the use of nonimaging, noninvasive laboratory methods for detecting relevant abnormalities, and the frequency and possible correlation of coagulation abnormalities with CNS lesions. In this cross-sectional study, 24 young patients with thalassemia intermedia were evaluated (mean age 12 ± 4.6 years, range 4.5-20 years). Patients underwent neurological examination, inherited and acquired coagulation defect testing, as well as neurophysiologic and neuroimaging evaluation. Patients aged 6-16 also had intelligence scores measured. With regards to coagulation, a decrease in antithrombin III (ATIII), protein C and protein S activity was found in 4.1, 54.16 and 45.8% of patients, respectively. Increased D-dimers, as well as thrombin-antithrombin complex (TAT) and prothrombin fragment (F1 + 2) values were found in 12.5, 62.5 and 8.33% of patients, respectively. Heterozygosity and homozygosity for the methylenetetrahydrofolate reductase mutation was found in 45.8 and 12.5% of patients, whereas heterozygosity for factor V Leiden and G20210FII was found in 8.33 and 12.5% of patients, respectively, with increased prevalence compared to Greek population. Neuroimaging evaluation was normal in all patients. Neurophysiologic evaluation revealed abnormal findings in 33.3% of patients on electroencephalogram (EEG), 16% on brain auditory-evoked potentials (BAEPs) and 4.12% on somatosensory evoked potentials (SEPs). Visual-evoked potentials (VEPs) were normal in all patients. A statistically significant difference was found between low protein C values, as well as high platelet counts, with abnormal EEG findings (P = 0.004 and P = 0.039, respectively). Transcranial Doppler (TCD) measurements revealed increased peak systolic velocities in anterior and posterior cerebral arteries and in basilar artery in 57, 38 and 41% of patients, respectively, as compared to healthy population values. On the contrary, decreased mean velocities were found both on middle cerebral artery and pars terminalis of internal carotid examination in 28.5% of patients. Patients with pathological findings on TCD study had lower hematocrit (P = 0.049) and younger age (P = 0.001) than patients with normal measurements. With regards to intelligence scores, mean intelligence quotient (IQ) was 100 ± 19.1, with 11.7% of patients demonstrating IQ below 85. The study results confirm the early presence of hemostatic changes in patients with thalassemia intermedia. Additionally, they demonstrate subclinical CNS involvement starting at childhood. For such involvement detection, in addition to neuroimaging, neurophysiological and neuropsychological evaluation is warranted.
Asunto(s)
Coagulación Sanguínea , Sistema Nervioso Central/fisiopatología , Talasemia beta/fisiopatología , Adolescente , Antitrombina III/análisis , Estudios de Casos y Controles , Sistema Nervioso Central/metabolismo , Niño , Preescolar , Estudios Transversales , Electroencefalografía , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Grecia , Humanos , Masculino , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Mutación , Pruebas Neuropsicológicas , Péptido Hidrolasas , Recuento de Plaquetas , Proteína C/análisis , Proteína S/análisis , Adulto Joven , Talasemia beta/sangre , Talasemia beta/genéticaRESUMEN
Recent evidence supports the presence of renal dysfunction even among young patients with ß-thalassemia major. However, the possible genetic contribution has never been investigated. The aim of this study was to correlate the presence of Fok-I polymorphism of the vitamin D receptor gene with abnormal levels of early markers of renal impairment in children and young adults with thalassemia. Thirty-four patients (19 male and 15 female) with ß-thalassemia major on conventional treatment, with a mean decimal age of 14.62 ± 5.47 years (range: 5-22 years), were included in the study. Markers of renal function were determined in serum and in urine and patients were genotyped for Fok-I gene polymorphism. Genotype frequencies were similar to those previously reported for other populations: 47.06% of the patients were homozygous for the F allele, 41.18% were heterozygous, and 11.76% were homozygous for the f allele. A considerable number of patients demonstrated impaired renal function with increased serum cystatin C levels (29.41%), glomerular dysfunction with proteinuria (68%), as well as significant tubulopathy with hypercalciuria (73.08%), and increased levels of urinary ß(2)-microglobulin (29.41%). When patients were stratified according to Fok-I polymorphism, a significantly higher prevalence of abnormally increased serum levels of cystatin C was observed in patients being homozygous for the f allele (75%) compared with those being heterozygous (Ff) or homozygous for the F allele (14.29% and 31.25%, respectively, P = .02). Further studies are needed to confirm these preliminary results and elucidate the possible mechanisms involved.
Asunto(s)
Alelos , Frecuencia de los Genes , Enfermedades Renales/genética , Polimorfismo de Longitud del Fragmento de Restricción , Receptores de Calcitriol/genética , Talasemia beta/genética , Adolescente , Adulto , Biomarcadores/sangre , Biomarcadores/orina , Calcio/orina , Niño , Preescolar , Cistatina C/sangre , Femenino , Genotipo , Mesangio Glomerular/metabolismo , Humanos , Enfermedades Renales/sangre , Enfermedades Renales/orina , Masculino , Proteinuria/sangre , Proteinuria/orina , Receptores de Calcitriol/metabolismo , Microglobulina beta-2/orina , Talasemia beta/sangre , Talasemia beta/orinaAsunto(s)
Hierro/metabolismo , Pruebas de Función Respiratoria/métodos , Talasemia beta/metabolismo , Adolescente , Adulto , Femenino , Humanos , Sobrecarga de Hierro , Hígado/metabolismo , Imagen por Resonancia Magnética , Masculino , Miocardio/metabolismo , Pruebas de Función Respiratoria/instrumentación , Adulto Joven , Talasemia beta/epidemiologíaRESUMEN
Most of the biological actions of vitamin D are mediated by an intracellular receptor (VDR) in which several single nucleotide gene polymorphisms have been identified. Vitamin D deficiency is increasingly identified among thalassemic patients and recent evidence links it with myocardial iron accumulation. The aim of this work was to assess the distribution of the Fok-I polymorphism of the VDR gene among Greek children and young adults with beta-thalassemia major and to investigate its association with 25(OH)D(3) and 1,25(OH)(2)D(3) serum levels. Sixty-nine thalassemic patients (35 females and 34 males), with a mean age of 23·05±6·07â years, participated in the study. Genotype frequencies of Fok-I were similar to those previously reported for other populations; 44·9% of the patients were homozygotes for F allele, 43·5% were heterozygotes and 11·6% were homozygotes for the f allele. Low levels of serum 25(OH)D(3) were recorded, as 41 patients (59·4%) were below the cut-off limit of 50â nmol/l that determines deficiency, whereas, levels of 1,25(OH)(2)D(3) showed wide variability ranging from deficiency (≤50 pmol/l) in 34 patients (49·3%) to excess (≥125 pmol/l) in 13 patients (18·8%). When stratifying patients according to serum 1,25(OH)(2) D(3) concentrations, a higher prevalence of the f allele was observed in the deficiency group (P = 0·03). A comparison of the serum concentrations of the two vitamin D metabolites produced a trend towards a negative correlation (r = -0·204, P = 0·09). Further studies are required to assess the genetic contribution to the regulation of vitamin D metabolites in the serum of patients with beta-thalassemia major.
Asunto(s)
Receptores de Calcitriol/genética , Vitamina D/sangre , Talasemia beta/sangre , Talasemia beta/genética , Adolescente , Adulto , Niño , Femenino , Genotipo , Humanos , Masculino , Polimorfismo Genético , Vitamina D/genética , Adulto JovenRESUMEN
The severe endothelial dysfunction in children with acute lymphoblastic leukemia (ALL) can result from the disease itself, from treatment, or from other conditions (e.g. sepsis). The aim of this study was to determine the levels of markers of endothelial activation in children with ALL and to assess their potential prognostic value. Fifty-two children with ALL, 19 children with ALL 1-10 years after the completion of therapy, and 28 healthy children were studied. In children with ALL, there was a significant increase in thrombomodulin (TM) and von Willebrand factor (vWF) levels during the acute phase of the disease and during treatment. Children with an unfavorable outcome had higher levels of TM. In conclusion, severe endothelial dysfunction is present during the acute phase of ALL and during treatment and appears to result from the disease itself. Serum TM and vWF levels might represent additional, but not independent, prognostic markers in childhood ALL.
Asunto(s)
Endotelio Vascular/fisiopatología , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Trombomodulina/sangre , Factor de von Willebrand/análisis , Enfermedad Aguda , Adolescente , Biomarcadores/sangre , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Pronóstico , Resultado del TratamientoRESUMEN
Recent studies report reduced bone mineral density (BMD) even among young adults and children with hemophilia. Our aim was to assess bone status in children and adolescents with hemophilia with 2 methods: Quantitative UltraSonography (QUS) and Dual energy x-ray Absorptiometry (DXA), and consequently to investigate the degree of correlation between them. Twenty-seven patients (17 with severe hemophilia; residual factor activity <1% and 10 with moderate hemophilia) participated in the study. Mean age was 12.28±4.48 y (range: 4.94 to 18.00 y). All patients were evaluated with QUS at radius and at tibia and had DXA scan at lumbar spine. Anthropometric parameters were measured using standard techniques and joint evaluation was carried out using the Hemophilia Joint Health Score (HJHS). Only 2 out of 27 patients (7.5%) had BMD Z-scores <-2, whereas another 4 patients (15%) had BMD Z-scores between -1 and -2. QUS values in both radius and tibia were generally within the normal limits as only 1 patient had radius and another 1 had tibia QUS Z-score <-2. HJH scores were significantly although negatively correlated to Z-scores of tibia QUS (r=-0.455, P=0.034). No correlations were observed between lumbar BMD and radius or tibia QUS and no agreement was recorded between QUS and DXA in identifying patients at risk for osteoporosis (k=0.262). In conclusion, our study showed that only a small number of children and young adults with hemophilia have impaired bone properties as assessed both by DXA and QUS; no correlation was observed between these 2 methods.
Asunto(s)
Densidad Ósea , Enfermedades Óseas Metabólicas , Hemofilia A/epidemiología , Osteoporosis , Absorciometría de Fotón , Adolescente , Antropometría , Enfermedades Óseas Metabólicas/diagnóstico por imagen , Enfermedades Óseas Metabólicas/epidemiología , Niño , Preescolar , Humanos , Vértebras Lumbares/diagnóstico por imagen , Masculino , Osteoporosis/diagnóstico por imagen , Osteoporosis/epidemiología , Prevalencia , Radio (Anatomía)/diagnóstico por imagen , Factores de Riesgo , Tibia/diagnóstico por imagen , UltrasonografíaRESUMEN
There are limited studies on renal involvement in beta-thalassemia, mainly involving patients on deferoxamine, reporting both glomerular and tubular dysfunction. The aim of the present study was to investigate renal involvement in young thalassemia patients, using both conventional and early markers of renal dysfunction, and to correlate findings to iron chelation therapy. Forty-two patients aged 4-23 years were studied and, for analysis purposes, were divided into two groups based on chelation therapy (group A receiving deferasirox and group B receiving deferoxamine and deferiprone combination therapy). In addition to conventional renal biochemistries, creatinine clearance, estimated glomerular filtration rate, serum cystatin C (Cys C), fractional excretion of sodium, tubular phosphorus reabsorption and urine calcium, protein, beta(2)-microglobulin (beta(2)-MG) and glucose levels were measured. A considerable number of patients demonstrated impaired renal function with elevated Cys C levels (36%), glomerular dysfunction with proteinuria (24%) and tubulopathy with hypercalciuria (35.5%) and elevated excretion of beta(2)-MG (33.5%). Renal involvement seems to be present even in young patients with beta-thalassemia, therefore, routine use of early markers of renal dysfunction is recommended. Further studies are needed in order to investigate the role of new chelators in tubular function parameters.
Asunto(s)
Benzoatos/efectos adversos , Deferoxamina/efectos adversos , Quelantes del Hierro/efectos adversos , Enfermedades Renales/complicaciones , Piridonas/efectos adversos , Triazoles/efectos adversos , Talasemia beta/tratamiento farmacológico , Adolescente , Adulto , Benzoatos/uso terapéutico , Biomarcadores/sangre , Biomarcadores/orina , Terapia por Quelación/efectos adversos , Niño , Preescolar , Cistatina C/sangre , Deferasirox , Deferiprona , Deferoxamina/uso terapéutico , Quimioterapia Combinada , Diagnóstico Precoz , Femenino , Humanos , Hipercalciuria , Quelantes del Hierro/uso terapéutico , Enfermedades Renales/sangre , Enfermedades Renales/inducido químicamente , Enfermedades Renales/orina , Pruebas de Función Renal , Masculino , Proteinuria , Piridonas/uso terapéutico , Triazoles/uso terapéutico , Adulto Joven , Microglobulina beta-2/orina , Talasemia beta/sangre , Talasemia beta/complicaciones , Talasemia beta/orinaAsunto(s)
Eliminación de Gen , Hemoglobinas Anormales/genética , Talasemia alfa/genética , Niño , Humanos , MasculinoAsunto(s)
Hemofilia A/sangre , Osteoclastos/metabolismo , Osteoprotegerina/sangre , Ligando RANK/sangre , Adolescente , Niño , Preescolar , Humanos , Masculino , Osteocalcina/sangreRESUMEN
OBJECTIVES: Despite advances in conventional treatment, iron-induced cardiomyopathy is still the most frequent cause of death among patients with beta-thalassaemia major. Recent studies have correlated increased myocardial iron content to decreased levels of vitamin D in thalassaemic patients. The aim of this study was to measure parathormone (PTH) and metabolites of vitamin D and consequently to investigate whether these parameters predispose to myocardial iron overload in patients with beta-thalassaemia major. METHODS: In 62 patients (29 M and 33 F, mean age: 22.79 +/- 6.18 yr) with beta-thalassaemia major levels of intact parathormone (iPTH) and vitamin D metabolites [25(OmicronH)D(3) and 1,25(OmicronH)(2)D(3)] were measured in serum. Additionally, estimation of myocardial iron content was performed by magnetic resonance imaging, whereas mean serum ferritin concentrations were calculated for 1 yr prior to the study. RESULTS: Results showed markedly decreased levels of serum 25(OH)D(3) in 37 patients (60%), whereas 7 patients (11%) had borderline 25(OH)D(3) levels (between 50 and 75 nmol/L). Serum iPTH levels were significantly higher in patients having increased myocardial iron compared to those having normal myocardial iron (44.04 +/- 22.09 pg/mL vs. 31.39 +/- 14.30 pg/mL, P = 0.017). Multivariant regression analysis identified PTH levels as the major predictor of increased myocardial iron.
Asunto(s)
Sobrecarga de Hierro/etiología , Hierro/análisis , Miocardio/química , Hormona Paratiroidea/sangre , Reacción a la Transfusión , Deficiencia de Vitamina D/etiología , Talasemia beta/terapia , Adolescente , Adulto , Calcifediol/sangre , Calcitriol/sangre , Niño , Femenino , Ferritinas/sangre , Humanos , Hierro/sangre , Sobrecarga de Hierro/patología , Imagen por Resonancia Magnética , Masculino , Miocardio/patología , Deficiencia de Vitamina D/sangre , Adulto Joven , Talasemia beta/sangre , Talasemia beta/patologíaRESUMEN
The aim of this study was to provide reference standards for measurements of quantitative ultrasonography (QUS) of radius and tibia in normative Greek pediatric population. Analysis was performed in 1549 healthy subjects (814 girls and 735 boys) with a mean decimal age of 11.41+/-3.52 yr (range: 3.78-18.33 yr). Results showed a gradual increase of absolute values of radial and tibial speed of sound (SOS), with aging and with pubertal progressing, in both girls and boys. Gender comparison showed significantly increased SOS values measured both at radius and at tibia in girls more than 13 yr of age compared with aged-matched boys. Significant but mild correlation was noted between standard deviation scores (SDS) of SOS at radius and at tibia (r = 0.259, p < 0.001). Additionally, tibial SOS SDS were significantly negatively correlated with body mass index (BMI) SDS (r = -0.230, p < 0.001). Finally, subjects that spend more than 3h of daily "screen time" (television and personal computer) showed significantly decreased SOS values measured both at radius and at tibia. On the contrary, no correlation was observed between SOS values and the amount of physical activity reported.
Asunto(s)
Densidad Ósea , Radio (Anatomía)/diagnóstico por imagen , Tibia/diagnóstico por imagen , Adolescente , Factores de Edad , Índice de Masa Corporal , Remodelación Ósea/fisiología , Niño , Preescolar , Femenino , Grecia , Humanos , Estilo de Vida , Masculino , Valor Predictivo de las Pruebas , Radio (Anatomía)/fisiología , Valores de Referencia , Reproducibilidad de los Resultados , Factores Sexuales , Tibia/fisiología , UltrasonografíaRESUMEN
Our aim was to assess liver iron content, in thalassaemic patients, by using three different MR protocols and compare their data. Ninety-four thalassaemic patients (44 M and 50 F, mean age 25.82 +/- 8.3 yrs), were enrolled in the study. In each patient, three measurements of the liver iron content were performed, with the use of a single imager, equipped with a 1.5 Tesla magnet. Liver R2* was measured on gradient-echo sequence. Calculation of MR-HIC values was based on an algorithm using liver to muscle (L/M) ratios in five axial gradient-echo sequences. Finally, determination of liver R2 employed a 16-echo, spin-echo pulse sequence. Additionally, myocardial R2* value was determined for each patient. Results showed that all three magnetic resonance imaging (MRI) methods were highly correlated to each other and significantly correlated to serum ferritin concentrations. Liver R2 method showed an increased sensitivity in detecting liver iron contents in the upper range. No correlation occurred between each liver MRI parameter and myocardial R2* values. Finally, we managed to provide formulae for equating values obtaining with any of these three MRI methods.
Asunto(s)
Hierro/análisis , Hígado/química , Imagen por Resonancia Magnética/métodos , Talasemia/metabolismo , Adolescente , Adulto , Algoritmos , Femenino , Humanos , Imagen por Resonancia Magnética/normas , Masculino , Miocardio/metabolismo , Adulto JovenRESUMEN
Deferiprone (L1), has previously been reported to be associated with immunological abnormalities in iron loaded thalassemia patients. However, other factors may also have similar effects such as the level of iron overload, chronic immuno-stimulation due to transfusions, splenectomy and deferoxamine (DFO). During chelation therapy with DFO, several complications have been reported, which were due to pharmacological activity and high dose toxicity with regard to both acoustic and visual effects, as well as peripheral nerve disorders that were measured by nerve conduction velocities. The immune and neural status of 44 beta-thalassemic patients, aged 10-30 years (mean 19.4 +/- 4.9), receiving L1 as a monotherapy (n = 21), or in combination with DFO (n = 23), has been followed for 2 years by monitoring the level of immunoglobulins (IgG, IgM, IgA), the level of T and B lymphocytes (CD4/CD8), the auto antibodies: anti nuclear (ANA), anti-double-stranded (anti-ds DNA), anti reticulin (anti-R1), anti-extra nuclear (anti-ENA), anti histone (anti-AHA), anti liver-kidney-muscle (anti-LKM), anti-smooth muscle (anti-SMA), anti-thyroid (anti-ATA), anti-mitochondrial (anti-AMA) antibodies and the C-reactive protein. The percentage of patients with disorders of the immune and nervous system concerned very few cases. None of our patients with pathological findings in their immunological or neurophysiological examinations presented any signs or symptoms of involvement of the immune or nervous system. Further advantages have been identified for the oral use of L1 and its combination with DFO, including synergistic efficacy and lower dosing with limited toxicity.
Asunto(s)
Potenciales Evocados , Sistema Inmunológico/fisiología , Talasemia beta/tratamiento farmacológico , Adolescente , Adulto , Autoanticuerpos/sangre , Linfocitos B/inmunología , Terapia por Quelación , Niño , Deferiprona , Deferoxamina/administración & dosificación , Deferoxamina/uso terapéutico , Quimioterapia Combinada , Ferritinas/sangre , Humanos , Factores Inmunológicos/sangre , Quelantes del Hierro/uso terapéutico , Sobrecarga de Hierro/tratamiento farmacológico , Piridonas/administración & dosificación , Piridonas/uso terapéutico , Linfocitos T/inmunología , Talasemia beta/inmunología , Talasemia beta/fisiopatologíaRESUMEN
OBJECTIVE: Osteopenia/osteoporosis of multi-factorial pathogenetic mechanism is reported to be a significant cause of morbidity in adult patients with beta-thalassaemia major. Even in young patients, decreased Bone Mineral Density (BMD) values are a consistent finding in the literature. This study was performed in order to assess BMD in children and young adults with beta-thalassaemia major, regularly transfused and sufficiently chelated, along with auxological, clinical and laboratory parameters. DESIGN: Thirty-five young thalassaemic patients (19 F, 16 M, aged 5-20 yr) were studied. Lumbar BMD was assessed by dual X-ray absorptiometry (DXA) and Z-scores were calculated according to bone density values using age- and sex-matched normal population. None of the patients presented with clinical or laboratory signs of endocrinopathy and none was receiving hormonal replacement therapy. RESULTS: All BMD Z-scores were within normal range, with a mean Z-score of 0.42 for girls and -0.41 for boys (statistically significant gender difference, p=0.018). When correlated with age, a decline in Z-scores was observed, indicating a delay in bone mass acquisition with advancing age in the thalassaemic group compared to controls. CONCLUSIONS: Optimal conventional treatment prevents the manifestation of osteopenia/osteoporosis during the first two decades of life in patients with beta-thalassaemia major. However, close surveillance with regular screening, preventive intervention and early management of possible endocrine complications are essential in order to secure normal bone health during adulthood and improve quality of life in the thalassaemic population.
Asunto(s)
Densidad Ósea , Talasemia beta/fisiopatología , Talasemia beta/terapia , Absorciometría de Fotón , Adolescente , Adulto , Transfusión Sanguínea , Estatura , Quelantes/uso terapéutico , Niño , Preescolar , Deferiprona , Deferoxamina/uso terapéutico , Femenino , Humanos , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/análisis , Vértebras Lumbares , Masculino , Piridonas/uso terapéuticoRESUMEN
Hemophilic pseudotumor is an uncommon complication seen in approximately 1-2% of patients with severe hemophilia. Hemophilic pseudotumors are distinguished into two subdivisions based on location, proximal or distal. Plain x-rays and CT are useful in diagnosis, but MR imaging is the diagnostic test of choice because of its sensitivity to the various blood products. The choice of therapy depends on many parameters, such as the size of the tumor, the age of the patient, and the relation with underlying organs. In most cases of asymptomatic hemophilic pseudotumor, conservative treatment with administration of missing factor as well as immobilization is recommended. The authors describe a 13-year-old boy with severe hemophilia A, who presented with a tibial pseudotumor a few months after an injury. He was conservatively treated for a long period, with daily administration of recombinant factor VIII. His clinical condition improved shortly after therapy induction, but radiological improvement has been moderate. Case history, imaging findings, and therapeutic options are discussed.
Asunto(s)
Neoplasias Óseas/diagnóstico por imagen , Hemofilia A/diagnóstico por imagen , Tibia/diagnóstico por imagen , Adolescente , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/etiología , Diagnóstico Diferencial , Factor VIII/administración & dosificación , Hemofilia A/complicaciones , Hemofilia A/tratamiento farmacológico , Humanos , Imagen por Resonancia Magnética , Masculino , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: To assess insulin sensitivity in young adult normoglycemic beta-thalassaemia major patients. METHODS: We measured insulin sensitivity with the euglycemic insulin clamp in 10 young adult (mean age 24.85 +/- 2.45 yrs) normoglycemic beta-thalassaemia major patients and 10 sex- & age-matched controls. Liver iron accumulation was assessed by magnetic resonance imaging (MRI). RESULTS: Glucose infusion rate (M) required to maintain euglycemia was significantly reduced in thalassaemic patients compared to controls (261.5 +/- 63.5 mg/m2 x min vs. 355.6 +/- 35.3 mg/m2 x min, P = 0.008). Consequently, significantly reduced in the thalassaemic group were also tissue sensitivity to insulin (M/I(s-s)) and glucose metabolic clearance rate (M/G(s-s)). There was significant negative correlation between ferritin levels and glucose infusion rate (r = -0.918 P = 0.004). No significant correlations were observed between age, body mass index, daily transfusional iron accumulation, liver iron content and any of the euglycemic clamp parameters. Fasting insulin levels were significantly increased in patients with beta-thalassaemia major compared to controls (P = 0.01), and had significant negative correlation to MRI-derived liver iron content (r = -0.733, P = 0.03). CONCLUSIONS: Our data indicate that reduced insulin sensitivity resulting in hyperinsulinaemia precedes the manifestation of glucose intolerance in patients with beta-thalassaemia major. Insulin resistance seems to correlate with increased serum ferritin levels.