RESUMO
Excessive intravascular release of lysed cellular contents from damaged red blood cells (RBCs) in patients with sickle cell anemia (SCA) can activate the inflammasome, a multiprotein oligomer promoting maturation and secretion of proinflammatory cytokines, including interleukin-1ß (IL-1ß). We hypothesized that IL-1ß blockade by canakinumab in patients with SCA would reduce markers of inflammation and clinical disease activity. In this randomized, double-blind, multicenter phase 2a study, patients aged 8 to 20 years with SCA (HbSS or HbSß0-thalassemia), history of acute pain episodes, and elevated high-sensitivity C-reactive protein >1.0 mg/L at screening were randomized 1:1 to received 6 monthly treatments with 300 mg subcutaneous canakinumab or placebo. Measured outcomes at baseline and weeks 4, 8, 12, 16, 20, and 24 included electronic patient-reported outcomes, hospitalization rate, and adverse events (AEs) and serious AEs (SAEs). All but 1 of the 49 enrolled patients were receiving stable background hydroxyurea therapy. Although the primary objective (prespecified reduction of pain) was not met, compared with patients in the placebo arm, patients treated with canakinumab had reductions in markers of inflammation, occurrence of SCA-related AEs and SAEs, and number and duration of hospitalizations as well as trends for improvement in pain intensity, fatigue, and absences from school or work. Post hoc analysis revealed treatment effects on weight, restricted to pediatric patients. Canakinumab was well tolerated with no treatment-related SAEs and no new safety signal. These findings demonstrate that the inflammation associated with SCA can be reduced by selective IL-1ß blockade by canakinumab with potential for therapeutic benefits. This trial was registered at www.clinicaltrials.gov as #NCT02961218.
Assuntos
Anemia Falciforme , Anticorpos Monoclonais , Anemia Falciforme/complicações , Anemia Falciforme/tratamento farmacológico , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Biomarcadores , Criança , Método Duplo-Cego , Humanos , Inflamação/tratamento farmacológico , Adulto JovemRESUMO
The blood counts of α thalassemia carriers (α-thal) are similar to those of ß thalassemia carriers, except for Hemoglobin A2 (Hb A2), which is not elevated. The objective of this study was to determine whether mathematical formulas are effective for detecting suspected α-thal. The data were obtained from the database of the prevention program for detecting couples at risk for having a child with hemoglobinopathy. Red Blood Cells (RBC) indices were analyzed using mathematical formulas, and the sensitivity and negative predictive value (NPV) were calculated. Among 1334 blood counts suspected of α-thal analyzed, only the Shine and Lal and the Support Vector Machine formulas revealed high sensitivity and NPV. Sensitivity was 85.54 and 99.33%, and NPV was 98.93 and 99.93%, respectively. Molecular defects were found in 291, and 81 had normal α genes. Molecular analysis was not performed in 962 of the samples. Based on these results, mathematical formulas incorporating one of these reliable formulas for detecting suspected α or ß thalassemia carriers in the program of the automatic analyzers can flag these results, increase the awareness of the primary physicians about the carrier risk, and send an alert with a recommendation for further testing.
Assuntos
Máquina de Vetores de Suporte , Talassemia alfa , Humanos , Talassemia alfa/diagnóstico , Talassemia alfa/genética , Talassemia alfa/sangue , Heterozigoto , Feminino , Masculino , Índices de Eritrócitos , Talassemia beta/diagnóstico , Talassemia beta/genética , Talassemia beta/sangue , Triagem de Portadores Genéticos/métodosRESUMO
In this issue, Hokland et al. offer an interesting view of the different approaches on how to treat a beta-thalassemia patient. The principal concerns, that this report reveals, are the very wide differences in the facilities and economic resources available for the care of patients. Management of thalassemia should become a word wide health care priority and may include at last those two steps: national and international registries; national programs for screening couples at risk and providing preventive measures to prevent births of patients with thalassemia. Commentary on: Hokland et al. Thalassaemia-A global view. Br J Haematol. 2023;201:208-223.
Assuntos
Hemoglobinopatias , Talassemia alfa , Talassemia beta , Humanos , Talassemia beta/epidemiologia , Talassemia beta/terapia , Hemoglobinopatias/terapiaRESUMO
Severe protein C deficiency due to biallelic PROC mutations is an extremely rare thrombophilia, most commonly presenting during the neonatal period as purpura fulminans. Despite treatment, severe morbidity and mortality are frequent. The current study reports 3 unrelated patients harboring novel homozygous PROC mutations and their clinical phenotypes. We discuss how the cytoprotective activity of protein C and its role in the stabilization of endothelial barriers may account for the unique symptoms of this thrombophilia.
Assuntos
Deficiência de Proteína C/diagnóstico , Proteína C/genética , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinogênio/análise , Homozigoto , Humanos , Lactente , Recém-Nascido , Mutação , Fenótipo , Deficiência de Proteína C/genética , Deficiência de Proteína C/patologia , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Renal injury in transfusion dependent ß thalassemia patients (TDT) has been attributed to iron overload, chronic anemia and iron-chelation therapy (ICT) toxicity. We studied renal function in TDT patients treated with two different ICT regimes. PATIENTS AND METHODS: We studied 36 TDT patients: 26 received deferasirox (DFX) and 10 were treated with deferoxamine (DFO) +/- deferiprone (DFP). RESULTS: Increased uNAG was found in 30% of the DFX group vs. 10% of the DFO+/-DFP group, the mean uNAG level in the DFX group was significantly higher than in the DFO+/-DFP group, (P < 0.05). A moderate negative correlation was found between uNAG levels and mean serum ferritin for the prior 10 years (P = 0.03), more pronounced for the DFO+/-DFP group. Twenty nine patients had had their renal function evaluated 10 years earlier; eGFR significantly declined in patients switched to DFX (P = 0.0093) but not in patients who continued DFO+/-DFP. CONCLUSIONS: A high prevalence of renal tubular damage was observed in our TDT patients, particularly those treated with DFX; uNAG was negatively associated with mean 10-year serum ferritin, suggesting ICT's involvement in tubular injury. A significant decline in eGFR compared to a decade earlier was observed only in patients currently treated with DFX. Strict follow-up of renal function in TDT patients is warranted.
Assuntos
Deferasirox/uso terapêutico , Desferroxamina/uso terapêutico , Quelantes de Ferro/uso terapêutico , Rim/fisiopatologia , Talassemia beta/tratamento farmacológico , Talassemia beta/fisiopatologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Otogenic cerebral sinus vein thrombosis (CSVT) is a rare but severe complication of otitis media in children. To date, the role of prothrombotic evaluation is still controversial. OBJECTIVES: To report the clinical manifestations, prothrombotic evaluation, and current management of CSVT. METHODS: We performed a retrospective study of nine pediatric patients with otogenic CSVT who underwent prothrombotic evaluation between 2008 and 2018. RESULTS: Prominent clinical features included persistent otorrhea (88.8%), signs of mastoiditis (88.8%), high fever ≥ 38.3°C (100%), a classic spiking fever pattern (55.5%), and neurological signs (55.5%). A subperiosteal abscess (66.6%) was the most common otitis media complication associated with mastoiditis and CSVT. No microorganism was identified in 55.5% of patients. Cultures collected from ear secretions had a low yield (6.25%). However, PCR assays had a high detection rate (100%; n=3). The prothrombotic evaluation demonstrated an abnormal LAC-dRVVT ratio (6/9), elevated Factor VIII (5/8) (and a combination of both in four patients), antiphospholipid antibodies (2/8), and high homocysteine levels (1/5).The surgical intervention of choice included one-sided mastoidectomy with myringotomy and ventilation-tube placement on the affected side (77.7%). There were no mortalities and no long-term sequela except chronic otitis media (22.2%). CONCLUSIONS: Our findings demonstrate good outcomes for otogenic CSVT treatment with intravenous antibiotics, anticoagulation, and conservative surgical intervention, which supports the current trend in management. The prothrombotic evaluation revealed transient inflammation-related risk factors but did not alter management. Further prospective multicenter studies are needed to determine its relevance.
Assuntos
Mastoidite/etiologia , Otite Média/complicações , Trombose dos Seios Intracranianos/etiologia , Trombofilia/etiologia , Antibacterianos/administração & dosagem , Anticoagulantes/administração & dosagem , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Mastoidite/diagnóstico , Mastoidite/terapia , Ventilação da Orelha Média/métodos , Estudos Retrospectivos , Trombose dos Seios Intracranianos/diagnóstico , Trombose dos Seios Intracranianos/terapia , Trombofilia/diagnóstico , Trombofilia/terapiaRESUMO
Beta thalassemia major (ßT) is a hereditary anemia characterized by transfusion-dependency, lifelong requirement of chelation, and organ dysfunction. MicroRNA (miRNA) can be packed into extracellular vesicles (EVs) that carry them to target cells. We explored EV-miRNA in ßT and their pathophysiologic role. Circulating EVs were isolated from 35 ßT-patients and 15 controls. EV miRNA was evaluated by nano-string technology and real-time quantitative polymerase chain reaction (RT-qPCR). We explored effects of EVs on cell culture proliferation, apoptosis, and signal transduction. Higher amounts of small EV (exosomes) were found in patients than in controls. The expression of 21 miRNA was > two-fold higher, and of 17 miRNA < three-fold lower in ßT-EVs than control-EVs. RT-qPCR confirmed differential expression of six miRNAs in ßT, particularly miR-144-3p, a regulator of erythropoiesis. Exposure of endothelial, liver Huh7, and pancreatic 1.1B4 cells to ßT-EVs significantly reduced cell viability and increased cell apoptosis. ßT-EV-induced endothelial cell apoptosis involved the MAPK/JNK signal-transduction pathway. In contrast, splenectomized ßT-EVs induced proliferation of bone marrow mesenchymal stem cells (BM-MSC). In summary, the miR-144-3p was strongly increased; ßT-EVs induced apoptosis and decreased endothelial, pancreatic, and liver cell survival while supporting BM-MSC proliferation. These mechanisms may contribute to ßT organ dysfunction and complications.
Assuntos
Vesículas Extracelulares/metabolismo , MicroRNAs/metabolismo , Talassemia beta/complicações , Talassemia beta/metabolismo , Adolescente , Adulto , Apoptose/genética , Transporte Biológico , Estudos de Casos e Controles , Linhagem Celular , Sobrevivência Celular/genética , Exossomos/metabolismo , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Transdução de Sinais , Adulto Jovem , Talassemia beta/genéticaRESUMO
Fanconi anemia (FA), an inherited bone marrow failure (BMF) syndrome, caused by mutations in DNA repair genes, is characterized by congenital anomalies, aplastic anemia, high risk of malignancies and extreme sensitivity to alkylating agents. We aimed to study the clinical presentation, molecular diagnosis and genotype-phenotype correlation among patients with FA from the Israeli inherited BMF registry. Overall, 111 patients of Arab (57%) and Jewish (43%) descent were followed for a median of 15 years (range: 0.1-49); 63% were offspring of consanguineous parents. One-hundred patients (90%) had at least one congenital anomaly; over 80% of the patients developed bone marrow failure; 53% underwent hematopoietic stem-cell transplantation; 33% of the patients developed cancer; no significant association was found between hematopoietic stem-cell transplant and solid tumor development. Nearly 95% of the patients tested had confirmed mutations in the Fanconi genes FANCA (67%), FANCC (13%), FANCG (14%), FANCJ (3%) and FANCD1 (2%), including twenty novel mutations. Patients with FANCA mutations developed cancer at a significantly older age compared to patients with mutations in other Fanconi genes (mean 18.5 and 5.2 years, respectively, P=0.001); however, the overall survival did not depend on the causative gene. We hereby describe a large national cohort of patients with FA, the vast majority genetically diagnosed. Our results suggest an older age for cancer development in patients with FANCA mutations and no increased incidence of solid tumors following hematopoietic stem-cell transplant. Further studies are needed to guide individual treatment and follow-up programs.
Assuntos
Anemia de Fanconi , Anemia de Fanconi/genética , Proteína do Grupo de Complementação A da Anemia de Fanconi/genética , Proteína do Grupo de Complementação C da Anemia de Fanconi/genética , Estudos de Associação Genética , Humanos , Israel , MutaçãoRESUMO
BACKGROUND: Immune thrombocytopenia (ITP) is an autoimmune disorder of variable origin that results in bleeding and decreased platelet count. Autoimmune abnormalities have been described in patients with malignancies including non-Hodgkin's lymphoma but are rarely described in patients with Hodgkin's lymphoma. OBJECTIVES: To describe an unusual presentation of Hodgkin's lymphoma in an unusual age and alarm pediatricians of the challenging diagnosis. METHODS: We present two cases that highlight an unusual clinical presentation of childhood Hodgkin's lymphoma occurring at an atypical age. RESULTS: Over a 4-year period, two children aged 5 and 6 years were admitted for suspected ITP, both had cervical lymphadenopathy. Bone marrow examination showed no evidence of tumor or fibrosis. Biopsy of the lymph node was possible only after administration of intravenous immunoglobulins and normalization of the platelet count. Platelet counts increased after initiation of chemotherapy. CONCLUSIONS: The identification of the clinical presentation of ITP as a possible presentation of Hodgkin's lymphoma is important to facilitate timely diagnosis and management.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/complicações , Imunoglobulinas Intravenosas/administração & dosagem , Síndromes Paraneoplásicas/etiologia , Púrpura Trombocitopênica/tratamento farmacológico , Púrpura Trombocitopênica/etiologia , Biópsia por Agulha , Análise Química do Sangue , Criança , Pré-Escolar , Feminino , Seguimentos , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/imunologia , Humanos , Imuno-Histoquímica , Excisão de Linfonodo/métodos , Linfonodos/patologia , Masculino , Síndromes Paraneoplásicas/fisiopatologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Púrpura Trombocitopênica/fisiopatologia , Medição de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
We investigated neural correlates of cognitive function in adults with beta thalassaemia major (ß-TM) compared to healthy controls using scalp-recorded event-related potentials (ERPs). Event-related potential studies in the field of ß-TM are scarce and mostly limited to children. A stop-signal task was used to evaluate indices of attention and response inhibition function, considered to be the hallmark of executive control. Correlations between task performance, ERPs and haemoglobin were also examined. Results showed impaired cognitive performance in ß-TM patients, as indicated by longer response times than controls. Haemoglobin was negatively correlated with response times to Go stimuli. Electrophysiological results indicated significant ß-TM-related alterations in neuronal activity, reflected in greater peak amplitudes of several task-related ERP components. A possible interpretation of these ERP results is that ß-TM patients need to recruit additional brain resources when dealing with cognitive challenge. Significant correlations were found between levels of haemoglobin and amplitude of all ERP components; the lower the haemoglobin, the more pronounced the ERPs amplitude. The present study represents a novel investigation of cognitive function and related brain dynamics in ß-TM in adult. Integrating neuropsychological assessment and interventions into traditional disease management, may be imperative in achieving a better quality of life for these patients.
Assuntos
Atenção , Encéfalo/fisiopatologia , Cognição , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/psicologia , Potenciais Evocados , Talassemia beta/complicações , Adolescente , Adulto , Estudos de Casos e Controles , Disfunção Cognitiva/diagnóstico , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Adulto Jovem , Talassemia beta/diagnósticoRESUMO
Autoimmune lymphoproliferative syndrome (ALPS) is typically caused by mutations in genes of the extrinsic FAS mediated apoptotic pathway, but for about 30% of ALPS-like patients the genetic diagnosis is lacking. We analyzed 30 children with ALPS-like disease of unknown cause and identified two dominant gain-of-function mutations of the Signal Transducer And Activator Of Transcription 3 (STAT3, p.R278H, p.M394T) leading to increased transcriptional activity. Hyperactivity of STAT3, a known repressor of FAS, was associated with decreased FAS-mediated apoptosis, mimicking ALPS caused by FAS mutations. Expression of BCL2 family proteins, further targets of STAT3 and regulators of the intrinsic apoptotic pathway, was disturbed. Cells with hyperactive STAT3 were consequently more resistant to intrinsic apoptotic stimuli and STAT3 inhibition alleviated this effect. Importantly, STAT3-mutant cells were more sensitive to death induced by the BCL2-inhibitor ABT-737 indicating a dependence on anti-apoptotic BCL2 proteins and potential novel therapeutic options.
Assuntos
Apoptose/genética , Síndrome Linfoproliferativa Autoimune/genética , Fator de Transcrição STAT3/genética , Compostos de Bifenilo , Hidroxitolueno Butilado/análogos & derivados , Estudos de Casos e Controles , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Família , Proteína Ligante Fas/metabolismo , Feminino , Perfilação da Expressão Gênica , Mutação em Linhagem Germinativa , Humanos , Immunoblotting , Imunofenotipagem , Leucócitos Mononucleares , Linfócitos , Nitrofenóis , Piperazinas , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Sulfonamidas , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Receptor fas/metabolismoRESUMO
UNLABELLED: Hereditary sequence variants in globin genes are usually silent and are rarer in α-globin chains than ß-globin chains. Some may lead to an unstable protein with a hemolytic or thalassemic phenotype. Hb Taybe is an unstable α-chain hemoglobin variant caused by the deletion of a threonine residue at codon 38 or 39 of the α1 globin gene. This deletion results in a structural abnormality that affects the α1 ß2 contact and the α1 ß1 interface, producing a highly unstable Hb. OBJECTIVE: We describe the clinical, laboratory, and morphological characteristics of 43 patients with Hb Taybe, sixteen of whom are heterozygous, eight are homozygous, and nineteen are double heterozygous for Hb Taybe and other α-gene mutations or deletions. RESULTS: The clinical presentation is very variable from a mild hemolytic anemia to the need for red cell transfusion. Morphological characteristics include erythroid hyperplasia, defective hemoglobin production, and dyserythropoietic features. On electron microscopy dyserythropoiesis and cytoplasmic precipitation of globin compatible optical dense material is seen. CONCLUSIONS: This is the largest report of Hb Taybe patients. Previous reported cohorts are not related to these cases. We conclude that patients carrying Hb Taybe have a unique hematological and clinical phenotype distinct from other hemoglobinopathies and from congenital dyserythropoietic anemia.
Assuntos
Hemoglobinopatias/diagnóstico , Hemoglobinopatias/genética , Hemoglobinas Anormais/genética , Adolescente , Medula Óssea/patologia , Medula Óssea/ultraestrutura , Criança , Pré-Escolar , Códon , Consanguinidade , Índices de Eritrócitos , Feminino , Estudos de Associação Genética , Genótipo , Hemoglobinas Anormais/metabolismo , Humanos , Masculino , Fenótipo , alfa-Globinas/genéticaRESUMO
In young children, iron deficiency (ID)-the most common cause of anemia-may adversely affect long-term neurodevelopment and behavior. We prospectively evaluated the prevalence of ID and iron deficiency anemia (IDA) in 256 healthy 18- to 36-month-old children in Northern Israel. Complete blood count and ferritin evaluation were performed, and risk factors were assessed. Hemoglobin (Hgb) was compared with first-year routine screening. Complete data were obtained from 208 children: 56.2% were boys; the mean age was 26.1±5.27 months. A prevalence of 5.8% IDA, 16.3% ID without anemia, 9.6% anemia with normal ferritin, and 68.3% normal Hgb and ferritin was found. In nonanemic infants at 1 year of age (n=156), ID/IDA was found in 19.9%, and 12.8% became anemic at study evaluation. Despite iron supplementation in the first year, and normal Hgb at first-year screening, ID and IDA were still prevalent, and might develop during the second year of life. Recognition of this child subset and consideration of iron supplementation are mandatory.
Assuntos
Anemia Ferropriva/sangue , Anemia Ferropriva/epidemiologia , Pré-Escolar , Suplementos Nutricionais , Feminino , Ferritinas/sangue , Hemoglobinas/análise , Humanos , Ferro/sangue , Israel/epidemiologia , Masculino , Prevalência , Estudos ProspectivosRESUMO
BACKGROUND: The relative frequency of mutated genes among patients with severe congenital neutropenia (SCN) may differ between various ethnic groups. To date, few population-based genetic studies have been reported. This study describes the genetic analysis of 32 Israeli patients with SCN. PROCEDURES: Clinical data were retrieved from the prospective Israeli Inherited Bone Marrow Failure Registry. Recruitment included living and deceased patients who were diagnosed between 1982 and 2012, for whom molecular diagnosis was performed. ELANE, HAX1 and G6PC3 genes were sequenced in all patients, and GFI-1 and WAS genes were sequenced if other genes were wildtype. RESULTS: Eleven patients (34%) had heterozygous mutations in ELANE (10 kindreds), eight (25%) had homozygous mutations in G6PC3 (5 kindreds) and 13 (41%) had no detected mutations. No patients had mutations in HAX1 or WAS. Four of the eight patients with G6PC3 mutations had congenital anomalies. The probability of survival for all patients was 50% at age of 18. Deaths were mainly due to sepsis (5 patients, 4/5 not responding to G-CSF, none with G6PC3 mutation). Two patients developed acute myelogenous leukemia (AML) and one myelodysplastic syndrome (MDS), none with G6PC3 mutation. CONCLUSIONS: We found a unique pattern of SCN mutations in Israel with homozygous G6PC3 mutations in eight (25%) patients, the highest frequency described so far. HAX1 mutations, reported mainly in Sweden and Iran, were absent. Patients with G6PC3 mutations had congenital anomalies, appeared to have a better response to G-CSF, and so far have not developed AML or MDS.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Testes Genéticos , Glucose-6-Fosfatase/genética , Mutação/genética , Neutropenia/congênito , Adolescente , Criança , Pré-Escolar , Terapia Combinada , Síndrome Congênita de Insuficiência da Medula Óssea , Proteínas de Ligação a DNA/genética , Feminino , Seguimentos , Genótipo , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Homozigoto , Humanos , Lactente , Recém-Nascido , Israel/epidemiologia , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Masculino , Síndromes Mielodisplásicas/epidemiologia , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/terapia , Neutropenia/genética , Neutropenia/mortalidade , Neutropenia/patologia , Prognóstico , Estudos Prospectivos , Transplante de Células-Tronco , Taxa de Sobrevida , Fatores de Transcrição/genética , Proteína da Síndrome de Wiskott-Aldrich/genéticaRESUMO
Loxoscelism, characterized by high fever, vomiting, malaise, a dermonecrotic lesion, and thrombocytopenia, was diagnosed in a 3-year-old female. Clinical laboratory and dermatological signs are described. Blood test showed a transient hypercoagulable state and the presence of IgG antibodies against platelets, suggesting an immune-mediated mechanism for platelet destruction, in addition to the direct toxic effect of the spider venom. The finding of platelet antibodies after a Loxosceles spider bite has not been previously reported.
Assuntos
Autoanticorpos , Aranha Marrom Reclusa , Picada de Aranha , Trombocitopenia , Animais , Autoanticorpos/sangue , Autoanticorpos/imunologia , Pré-Escolar , Feminino , Humanos , Picada de Aranha/sangue , Picada de Aranha/complicações , Picada de Aranha/imunologia , Trombocitopenia/sangue , Trombocitopenia/etiologia , Trombocitopenia/imunologiaRESUMO
Thoracic empyema is an accumulation of purulent fluid in the pleural space presenting as a complication of bacterial pneumonia. The aims of the study were to present the incidence, demographic results, clinical presentation, laboratory and microbiology results, imaging and the therapeutic options. From January 1992 until December 2009 we collected data of children hospitalized with empyema in our medical center in north of Israel. Empyema was found in 53 pediatric patients. The median age of the patients was 3 years and 31 (58%) were male. Forty one (77%) of the cases were diagnosed in the last nine years. Fever, cough and respiratory distress were the most frequent clinical signs. In 29 (55%) patients pleural effusion was found at admission. Chest ultrasound was performed in 44 (83%) of the patients. Causative organisms were confirmed by culture in 35 patients. Positive culture was found in 17 (32%) patients in the pleural fluid. Streptococcus pneumoniae was the leading pathogen. The drugs the patients received at admission were penicillin in 21 cases, cefuroxime in19 cases and ceftriaxone in 11 cases. During hospitalization a change of antibiotic therapy was required, using mainly ceftriaxone and clindamycin. The pleural purulent fluid was drained by video assisted thoracoscopy surgery in 34 (64%) patients. All the children recovered. The incidence of empyema as a complication of community acquired pneumonia had increased in the last decade in our region. Streptococcus pneumoniae is the most common pathogen. Third generation cephalosprins and clindamycin can be suggested as a good empiric treatment.
Assuntos
Empiema Pleural/diagnóstico , Empiema Pleural/terapia , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Empiema Pleural/epidemiologia , Empiema Pleural/microbiologia , Feminino , Humanos , Incidência , Lactente , Israel/epidemiologia , Masculino , Pneumonia Pneumocócica/epidemiologia , Pneumonia Pneumocócica/microbiologia , Streptococcus pneumoniae/isolamento & purificação , Cirurgia Torácica VídeoassistidaRESUMO
We describe the clinical and laboratory features of a family of Arab ancestry and consanguinity. Five affected individuals were diagnosed in two sibships. All affected members have small platelets, severe to moderate thrombocytopenia of neonatal onset, increased bleeding tendency and bleeding complications such as: life-threatening massive hemoperitoneum due to corpus luteum rupture during ovulation and severe mucosal bleeding. The familial involvement and early onset of the disease support the presence of a congenital genetic disorder with an autosomal recessive inheritance pattern. This does not fit the clinical spectrum of any of the currently known thrombocytopenia disorders.
Assuntos
Genes Recessivos , Doenças Genéticas Inatas/genética , Hemoperitônio/genética , Linhagem , Trombocitopenia/genética , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , MasculinoRESUMO
The membrane-bound hemoglobin (Hb) fraction impacts red blood cell (RBC) rheology and metabolism. Therefore, Hb-RBC membrane interactions are precisely controlled. For instance, the signaling function of membrane-bound deoxy-Hb and the structure of the docking sites in the cytosolic domain of the anion exchanger 1 (AE-1) protein are well documented; however, much less is known about the interaction of Hb variants with the erythrocyte's membrane. Here, we identified factors other than O2 availability that control Hb abundance in the membrane-bound fraction and the possible variant-specific binding selectivity of Hb to the membrane. We show that depletion of extracellular Ca2+ by chelators, or its omission from the extracellular medium, leads to membrane-bound Hb release into the cytosol. The removal of extracellular Ca2+ further triggers the redistribution of HbA0 and HbA2 variants between the membrane and the cytosol in favor of membrane-bound HbA2. Both effects are reversible and are no longer observed upon reintroduction of Ca2+ into the extracellular medium. Fluctuations of cytosolic Ca2+ also impact the pre-membrane Hb pool, resulting in the massive transfer of Hb to the cellular cytosol. We hypothesize that AE-1 is the specific membrane target and discuss the physiological outcomes and possible clinical implications of the Ca2+ regulation of the intracellular Hb distribution.
Assuntos
Eritrócitos , Hemoglobinas , Humanos , Membrana Eritrocítica , Citosol , QuelantesRESUMO
Non-transferrin bound iron (NTBI) is commonly detected in patients with systemic iron overload whose serum iron-binding capacity has been surpassed. It has been perceived as an indicator of iron overload, impending organ damage and a chelation target in poly-transfused thalassemia patients. However, NTBI is a heterogeneous entity comprising various iron complexes, including a significant redox-active and readily chelatable fraction, which we have designated as "labile plasma iron" (LPI). We found that LPI levels can be affected by plasma components such as citrate, uric acid, and albumin. However, the inclusion of a mild metal mobilizing agent in the LPI assay (designated here as "eLPI"), at concentrations that do not affect transferrin-bound iron, largely overcomes such effects and provides a measure of the full NTBI content. We analyzed three distinct groups of poly-transfused, iron overloaded thalassemia patients: non-chelated children (3-13 yrs, Gaza, Palestine), chelated adolescents-young adults (13-28 yrs, Israel), and chelated adults (27-61 yrs, Israel) for LPI and eLPI. The eLPI levels in all three groups were roughly commensurate (r(2) = 0.61-0.75) with deferrioxamine-detectable NTBI, i.e., DCI. In older chelated patients, eLPI levels approximated those of LPI, but in poly-transfused unchelated children eLPI was notably higher than LPI, a difference attributed to plasma properties affected by labile iron due to lack of chelation, possibly reflecting age-dependent attrition of plasma components. We propose that the two formats of NTBI measurement presented here are complementary and used together could provide more comprehensive information on the forms of NTBI in patients and their response to chelation.
Assuntos
Ferro/metabolismo , Talassemia/metabolismo , Transferrina/metabolismo , Adolescente , Adulto , Quelantes/metabolismo , Criança , Pré-Escolar , Humanos , Ferro/sangue , Pessoa de Meia-Idade , Ácido Nitrilotriacético/metabolismo , Oxirredução , Ligação Proteica , Talassemia/sangue , Adulto JovemRESUMO
Cognitive impairment has been associated with anemia and iron deficiency; however, brain electrophysiological studies correlating red blood cell (RBC) indices and iron status to cognition in adulthood are scarce. We aimed to assess neurocognitive function in young adults of the general population and its correlation with RBC indices and iron status. Neurocognitive function was investigated using scalp-recorded event-related potentials (ERPs) within the context of a task-switching paradigm. ERPs and test performance were also compared across groups of "high"/"low" RBC and iron indices. Working memory was examined using the digit span test, in which mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), and ferritin were found to be significant predictors of test performance, with higher MCH/MCV/ferritin being associated with better test scores. In the switching task, MCH, MCV, and ferritin were found to be significant predictors of task performance, with higher MCH/MCV/ferritin levels associated with a lower percentage of errors. Electrophysiological results showed that MCH and MCV were significant predictors of ERPs amplitude, with lower MCH/MCV levels associated with greater amplitude, which may reflect compensatory processes. P1, N1, P2, and P3 were greater for the low MCH/MCV groups. This is the first evidence of association between levels of MCH/MCV and brain function while engaged in an executive function task; possibly reflecting brain iron availability.