RESUMO
A recent study identified a variant of the NUDT15 gene (rs116855232 C>T) associated with intolerance to thiopurine in Korean patients with Crohn's disease. This study prompted us to substantiate the finding in a Taiwanese population. Four hundred and four children with acute lymphoblastic leukemia (ALL), and 100 adults with chronic immune thrombocytopenic purpura or localized lymphoma having normal bone marrow were examined. Two candidate gene approaches, pyrosequencing for NUDT15 and TaqMan assay for thiopurine methyltransferase (TPMT) genotyping (rs1142345 A>G), were performed. We showed a risk allele frequency of NUDT15 of 11.6% in children with ALL and 15.5% in adults. By contrast, the risk allele frequency of TPMT was only 1.6% in children with ALL and 0.5% in adults. The high frequency of risk variant for NUDT15, but not the very low frequency of risk variant for TPMT, was closely associated with the intolerance to mercaptopurine in children with ALL in Taiwan, contrast to that of European descent. In regard to NUDT15 polymorphism, the maximal tolerable daily doses of mercaptopurine in homozygotes, heterozygotes and wild-type groups were 9.4 mg m-2, 30.7 mg m-2 and 44.1 mg m-2, respectively. The outcomes did not differ significantly among the different genotypes.
Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Mercaptopurina/efeitos adversos , Variantes Farmacogenômicos , Polimorfismo Genético , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Pirofosfatases/genética , Fatores Etários , Antimetabólitos Antineoplásicos/administração & dosagem , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Frequência do Gene , Estudos de Associação Genética , Heterozigoto , Homozigoto , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Masculino , Dose Máxima Tolerável , Mercaptopurina/administração & dosagem , Farmacogenética , Testes Farmacogenômicos/métodos , Fenótipo , Reação em Cadeia da Polimerase , Medicina de Precisão , Leucemia-Linfoma Linfoblástico de Células Precursoras/enzimologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Valor Preditivo dos Testes , Pirofosfatases/metabolismo , Fatores de Risco , Taiwan , Fatores de Tempo , Resultado do TratamentoRESUMO
Our study was designed to prospectively determine whether or not unrelated cord blood transplantation (CBT) can produce outcomes comparable to related donor transplantation for children with ß-thalassaemia. In 35 patients, 40 transplants were performed between October 2003 and September 2009. HLA matching at enrolment was 6/6 (n=8), 5/6 (n=16), 4/6 (n=27), or 3/6 (n=1) by low-resolution HLA-A, -B, and high-resolution DRB1. These patients received non-manipulated grafts without ex vivo expansion or T-cell depletion. The median number of nucleated and CD34+ cells infused was 7.8 × 10(7)/kg (range, 2.8-14.7 × 10(7)/kg) and 4.0 × 10(5)/kg (range, 1.7-19.9 × 10(5)/kg), respectively. The 5-year OS and thalassaemia-free survival after the first transplant were 88.3 and 73.9%, respectively. The cumulative incidence of TRM at 2 years was 11.7%. Fourteen patients developed chronic skin GVHD. Thirty patients were alive and transfusion-independent with a Lansky performance score ≥80% achieved between 6 and 76 months post transplant (median, 36 months). These data compare acceptably with the survival rates of related-donor BMT for thalassaemia and suggest that patients without an available HLA-compatible sibling but who have well-matched unrelated donors should also be considered for CBT.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Talassemia/mortalidade , Talassemia/terapia , Adolescente , Antígenos CD34/sangue , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Antígenos HLA , Teste de Histocompatibilidade , Humanos , Lactente , Depleção Linfocítica/métodos , Masculino , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida , Talassemia/sangue , Transplante HomólogoRESUMO
The long-term outcome of 1390 children with acute lymphoblastic leukemia (ALL), treated in two successive clinical trials (Taiwan Pediatric Oncology Group (TPOG)-ALL-97 and TPOG-ALL-2002) between 1997 and 2007, is reported. The event-free survival improved significantly (P=0.0004) over this period, 69.3+/-1.9% in 1997-2001 to 77.4+/-1.7% in 2002-2007. A randomized trial in TPOG-97 testing L-asparaginase versus epidoxorubicin in combination with vincristine and prednisolone for remission induction in standard-risk (SR; low-risk) patients yielded similar outcomes. Another randomized trial, in TPOG-2002, showed that for SR patients, two reinduction courses did not improve long-term outcome over one course. Decreasing use of prophylactic cranial irradiation in the period 1997-2008 was not associated with increased rates of CNS relapse, prompting complete omission of prophylactic cranial irradiation from TPOG protocols, beginning in 2009. Decreased use of etoposide and cranial irradiation likely contributed to the low incidence of second cancers. High-risk B-lineage ALL, T-cell, CD10 negativity, t(9;22), infant, and higher leukocyte count were consistently adverse factors, whereas hyperdiploidy >50 was a consistently favorable factor. Higher leukocyte count and t(9;22) retained prognostic significance in both TPOG-97 and TPOG-2002 by multivariate analysis. Although long-term outcome in TPOG clinical trials is comparable with results being reported worldwide, the persistent strength of certain prognostic variables and the lower frequencies of favorable outcome predictors, such as ETV6-RUNX1 and hyperdiploidy >50, in Taiwanese children warrant renewed effort to cure a higher proportion of patients while preserving their quality of life.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/terapia , Segunda Neoplasia Primária/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Criança , Pré-Escolar , Aberrações Cromossômicas , Terapia Combinada , Irradiação Craniana , Feminino , Seguimentos , Humanos , Imunofenotipagem , Lactente , Masculino , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Neoplasia Residual , Segunda Neoplasia Primária/genética , Segunda Neoplasia Primária/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prognóstico , Indução de Remissão , Fatores de Risco , Taxa de Sobrevida , Taiwan , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Use of unrelated cord blood (UCB) has become increasingly popular as a stem cell source, given the rapid availability and decreased potential of graft-versus-host disease. We sought to ascertain whether the use of UCB transplantation for pediatric patients changed the rates of unscheduled readmission. METHODS: We analyzed the rate, causes, and evolution of hospitalization among patients receiving UCB versus matched sibling bone marrow. A retrospective analysis of the data from 54 patients who received a matched sibling hematopoietic stem cell transplantation (HSCT; n = 25; 46.3%) versus an unrelated cord blood transplantation (CBT; n = 29; 53.7%) was performed on subjects treated between 1998 and 2006. Patients who died before discharge (n = 4) were excluded from the readmission analysis. RESULTS: A total of 50 patients were recruited for the analyses. Their median age was 6.7 years (range = 0.2-17 years). The median duration of hospitalization was 18 days shorter in the sibling HSCT group than in the unrelated CBT group. There were 89 readmissions in 25 patients (50%): 49 readmissions (55%) in the related HSCT and 40 (45%) in the unrelated CBT cohorts. Forty-two percent of readmissions were due to infections. Mortality following transplantation in 10 patients (19%) included sepsis (n = 3), intracranial hemorrhage (n = 1), pulmonary hemorrhage (n =1), and relapse (n = 5). Seven patients received HSCT from HLA-identical sibling donors and three from a cord blood donor. CONCLUSION: For both groups, infection was the most common reason for readmission followed by graft failure and extramedullary relapse. Although the median hospital stay was shorter in the sibling donor group, some uncertainty exists as to whether the increased risk for readmission was related to proportionally more malignancies or to the severity of the illness. After HSCT, there was a frequent use of hospital resources: 46% of patients were hospitalized for a median of 11 days. The resulting health expenses seem to be useful, since 81% of subjects survived at 36-month follow-up.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Readmissão do Paciente/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Doenças Hematológicas/mortalidade , Doenças Hematológicas/cirurgia , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/cirurgia , Humanos , Lactente , Tempo de Internação , Estudos Retrospectivos , Análise de Sobrevida , Sobreviventes , Transplante HomólogoRESUMO
c-KIT mutations have been described in core-binding factor (CBF) acute myeloid leukemia (AML) at diagnosis. The role of c-KIT mutations in the relapse of CBF-AML is not clear. The role of CSF1R mutation in the pathogenesis of AML remains to be determined. We analyzed receptor tyrosine kinases (RTKs) and Ras mutations on 154 children with AML. Also, we examined the paired diagnosis and relapse samples in CBF-AML. CBF-AML accounted for 27% (41/154). c-KIT mutations were detected in 41.5% of CBF-AML at diagnosis (6 in exon 8, 10 in exon 17 and 1 in both exons 8 and 17) , FLT3-TKD 2.7%, N-Ras mutations 7.3% and K-Ras mutations 4.9%. FLT3-LM and CSF1R mutations were not found in CBF-AML. The mutations of RTKs and Ras were mutually exclusive except for one patient who had both c-KIT and N-Ras mutations. Eight of the 41 CBF-AML patients relapsed; four patients retained the identical c-KIT mutation patterns as those at diagnosis, the remaining four without c-KIT mutations at diagnosis did not acquire c-KIT mutations at relapse. Our study showed that 54% of childhood CBF-AML had RTKs and/or Ras mutations; c-KIT but not CSF1R mutations play a role in the leukemogenesis of childhood CBF-AML.
Assuntos
Fatores de Ligação ao Core , Genes ras/genética , Leucemia Mieloide Aguda/genética , Mutação , Proteínas Proto-Oncogênicas c-kit/genética , Receptores Proteína Tirosina Quinases/genética , Receptor de Fator Estimulador de Colônias de Macrófagos/genética , Adolescente , Medula Óssea/patologia , Criança , Pré-Escolar , Análise Mutacional de DNA , Humanos , Leucemia Mieloide Aguda/etiologia , Recidiva , Fatores de TempoRESUMO
BACKGROUND AND OBJECTIVE: Anorganic bovine mineral coated with a cell-binding peptide (P-15) is superior to anorganic bovine mineral alone in the treatment of periodontal osseous defects. However, the molecular interactions between P-15 and periodontal ligament fibroblasts remain unclear. MATERIAL AND METHODS: We first compared the in vitro osteogenic activities between periodontal ligament fibroblasts cultured with anorganic bovine mineral alone and with the P-15/anorganic bovine mineral combination. We then harvested the periodontal ligament cell lysate, incubated it with various graft materials, and then washed it to remove unbound proteins. The bound proteins were eluted from graft materials and analyzed using electrophoresis, followed by mass spectrometry and then western blotting. Finally, a neutralizing antibody against one bound protein was added to the cell cultures to repeat the osteogenic assays to clarify its role in the in vitro effects of the P-15/anorganic bovine mineral combination. RESULTS: Cells treated with P-15/anorganic bovine mineral were more viable and showed greater osteogenic activities than cells treated with anorganic bovine mineral alone and the no-graft control. Annexin II, a mineralization-associated protein, bound to P-15/anorganic bovine mineral significantly more than to anorganic bovine mineral alone. The addition of neutralizing antibody for annexin II decreased the osteogenic activities of the P-15/anorganic bovine mineral combination. CONCLUSION: Annexin II of periodontal ligament fibroblasts interacted with the peptide of P-15, and was partially responsible for better in vitro osteogenesis in the P-15 graft.
Assuntos
Anexina A2/metabolismo , Matriz Óssea/transplante , Substitutos Ósseos/uso terapêutico , Durapatita/uso terapêutico , Osteogênese/fisiologia , Adulto , Fosfatase Alcalina/análise , Anexina A2/fisiologia , Antraquinonas , Western Blotting , Matriz Óssea/metabolismo , Calcificação Fisiológica/efeitos dos fármacos , Calcificação Fisiológica/fisiologia , Sobrevivência Celular , Células Cultivadas , Corantes , Meios de Cultivo Condicionados , Eletroforese em Gel de Poliacrilamida , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Masculino , Espectrometria de Massas , Osteogênese/efeitos dos fármacos , Ligamento Periodontal/efeitos dos fármacos , Ligamento Periodontal/metabolismo , Ligação ProteicaRESUMO
To augment graft cell dose, we evaluated the safety of the combined transplantation of two partially HLA-matched umbilical cord blood (UCB) units. Five patients with transfusion-dependent thalassemia, median age 11.1 years (range 10-13.1), received 2 UCB units after myeloablative conditioning. Cord blood units were a 4/6-HLA-match or better with the recipient, and contained a minimum combined pre-freeze CD34 cell dose of 3.0 x 10(5)/kg. All patients engrafted at a median of 15 days (range 12-19). Four patients with durable trilineage engraftment showed acute grade I-III GVHD; none developed extensive chronic GVHD until the date of last contact. The median times to red blood cell transfusion independence and platelet engraftment were 32 and 49 days after transplant, respectively. With a median follow-up of 18.5 months (range 11-32), four patients transplanted with UCB from two different partially HLA-matched donors were transfusion-independent. Therefore, transfusion of two partially HLA-matched UCB units is safe, and may overcome the cell-dose barrier that limits the use of UCB in long-term recipients of multiple transfusions for thalassemia.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Talassemia/terapia , Adolescente , Criança , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Transfusão de Eritrócitos , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro , Humanos , Masculino , Quimeras de Transplante , Transplante Homólogo/métodosRESUMO
To improve treatment results for children with de novo acute myeloid leukemia (AML), we introduced a novel protocol, Taiwan Pediatric Oncology Group-AML-97A, for AML other than acute promyelocytic leukemia (APL), for which modified conventional protocols were used. From January 1, 1997, to December 31, 2002, 141 children younger than 17 years old with de novo AML were enrolled. In total, 117 patients with non-APL AML were treated with induction therapy of idarubicin and cytarabine (Ara-C), postremission therapy with high-dose Ara-C - containing regimens for four monthly courses, and moderate-dose therapy with idarubicin and Ara-C for four monthly courses. The first 19 patients with APL were treated with all-trans retinoic acid, idarubicin and Ara-C, with the remaining five patients receiving all-trans retinoic acid and idarubicin, followed by maintenance therapy for 2 years. Stem cell transplantation was performed in 29 patients in first remission with a similar outcome as chemotherapy alone. The remission rate in the AML-97A study was 90%, the 5-year survival 51 +/- 5.3% (s.e.) and the 5-year event-free survival 50 +/- 4.8%; for APL, these were 100%, 86 +/- 7.0, and 75 +/- 9.8%. For the whole group, the 5-year survival was 57 +/- 4.7% and the 5-year event-free survival 54 +/- 4.4%. The AML-97A regimen was well tolerated.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/terapia , Leucemia Promielocítica Aguda/terapia , Transplante de Células-Tronco , Adolescente , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Indução de Remissão , Taiwan , Resultado do TratamentoRESUMO
CEBPalpha: mutations have been described in adult acute myeloid leukemia (AML) and conferred a favorable prognosis. However, CEBPalpha mutation has not been reported in children. We investigated 117 children with de novo AML using DNA PCR assay followed by sequencing for each PCR product. CEBPalpha mutations were detected in seven patients, four had FAB M2, two M1 and one M4. CEBPalpha mutations only occurred in patients with intermediate cytogenetics and not in 56 children with AML1-ETO, CBFbeta-MYH11, PML-RARalpha or MLL rearrangements. Five patients had mutations occurred in both N-terminal part and basic-leucine zipper (bZIP) domain, one had an N-terminal frameshift mutation and the remaining one had an inframe insertion in the bZIP domain. Cloning analysis on five samples carrying more than one mutations demonstrated one homozygous combined mutations and four heterozygous biallelic mutations. Four of seven CEBPalpha mutation(+) patients had cooperating mutations with FLT3-ITD or N-ras mutations compared to 27 in 109 CEBPalpha mutation(-) patients. Our results showed that CEBPalpha mutations occurred in 6% of childhood AML and most exhibited combined mutations in both N-terminal part and bZIP domain.
Assuntos
Proteína alfa Estimuladora de Ligação a CCAAT/genética , Leucemia Mieloide Aguda/genética , Mutação , Adolescente , Criança , Pré-Escolar , Células Clonais , Análise Mutacional de DNA/métodos , Frequência do Gene , Humanos , Lactente , Recém-Nascido , Reação em Cadeia da Polimerase/métodosRESUMO
AIM: Little is known about the influence of environmental factors on the epidemiology of idiopathic thrombocytopenic purpura (ITP). The role of Helicobacter pylori infection in relation to the development and/or persistence of ITP in infected patients remains controversial. Therapy used for eradicating H. pylori has led to a rise in platelet counts in a significant number of adult patients. but few paediatric studies have been undertaken to evaluate such treatment. The aim of this prospective study was to determine the prevalence of H. pylori and to evaluate whether H. pylori eradication can induce chronic ITP regression in children. METHODS: To investigate new, noninvasive techniques for diagnosis of H. pylori infection, an enzyme immunoassay for H. pylori antigens in faeces (HpSA) was evaluated. Patient eligibility criteria included isolated thrombocytopenia (< or = 50 x 10(9) L-(-1)) for more than 6 months without any identifiable cause and either normal or increased marrow megakaryocytes. H. pylori status was monitored before eradication and 4, 12, and 24 mo, after the end of treatment using Premier Platinum HpSA. RESULTS: In this study we evaluated 22 chronic ITP patients, 9 of whom were infected with H. pylori. Using repeated HpSA testing, we demonstrated for eradication of H. pylori after treatment in all infected patients. Five of the nine patients had increased platelet counts that persisted throughout the follow-up period. CONCLUSION: These results should stimulate additional research into the involvement of H. pylori infection in chronic ITP in childhood. This approach may offer an accepted algorithm at least for some of these patients.
Assuntos
Antibacterianos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Púrpura Trombocitopênica Idiopática/complicações , Adolescente , Anticorpos Antibacterianos/isolamento & purificação , Criança , Pré-Escolar , Doença Crônica , Feminino , Infecções por Helicobacter/complicações , Infecções por Helicobacter/imunologia , Humanos , Masculino , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Resultado do TratamentoRESUMO
Mutations of receptor tyrosine kinases are implicated in the constitutive activation and development of human hematologic malignancies. An internal tandem duplication (ITD) of the juxtamembrane domain-coding sequence of the FLT3 gene (FLT3-ITD) is found in 20-25% of adult acute myeloid leukemia (AML) and at a lower frequency in childhood AML. FLT3-ITD is associated with leukocytosis and a poor prognosis, especially in patients with normal karyotype. Recently, there have been three reports on point mutations at codon 835 of the FLT3 gene (D835 mutations) in adult AML. These mutations are located in the activation loop of the second tyrosine kinase domain (TKD) of FLT3 (FLT3-TKD). The clinical and prognostic relevance of the TKD mutations is less clear. To the best of our knowledge, there has been no report to describe FLT3-TKD mutations in childhood AML. In this pediatric series, FLT3-TKD mutations occurred in three of 91 patients (3.3%), an incidence significantly lower than that of FLT3-ITD (14 of 91 patients, 15.4%) in the same cohort of patients. None of them had both FLT3-TKD and FLT3-ITD mutations. Sequence analysis showed one each of D835 Y, D835 V, and D835 H. Of the three patients carrying FLT3-TKD, two had AML-M3 with one each of L- and V-type PML-RARalpha, and another one had AML-M2 with AML1-ETO. None of our patients with FLT3-TKD had leukocytosis at diagnosis. At bone marrow relapse, one of the four patients examined acquired FLT3-ITD mutation and none gained FLT3-TKD mutation.
Assuntos
Substituição de Aminoácidos , Leucemia Mieloide Aguda/genética , Leucemia Promielocítica Aguda/genética , Mutação Puntual , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Receptores Proteína Tirosina Quinases/genética , Adolescente , Criança , Pré-Escolar , Códon/genética , Subunidade alfa 2 de Fator de Ligação ao Core , Primers do DNA , Feminino , Humanos , Masculino , Proteínas de Neoplasias/genética , Proteínas de Fusão Oncogênica/genética , Reação em Cadeia da Polimerase , Estrutura Terciária de Proteína , Proteína 1 Parceira de Translocação de RUNX1 , Receptores de Superfície Celular/genética , Fator de Células-Tronco/genética , Fatores de Transcrição/genética , Tirosina Quinase 3 Semelhante a fmsRESUMO
OBJECTIVES: Idiopathic pulmonary haemosiderosis (IPH) is a rare but potentially lethal disorder. A retrospective analysis of documented cases of IPH in our hospital was conducted in order to study the clinical spectrum and radiographic features, and to explore therapeutic strategies. METHODS: A retrospective chart review was carried out, collecting medical records of patients with pulmonary haemo-siderosis at Chang Gung Children's Hospital (CGCH), a tertiary children's hospital in northern Taiwan. Secondary causes of pulmonary haemosiderosis were excluded. RESULTS: Five patients were diagnosed as having IPH over a 25-year period. The classical triad of IPH was found at initial presentation in only 2/5 patients. One patient had well-established pulmonary fibrosis, but no pulmonary symptoms. The clinical course of IPH was exceedingly variable, with a mean delay of 9 months before diagnosis was made. Bronchoalveolar lavage (BAL) confirmed IPH in 3/5 patients. Immunological abnormalities were noted in two patients, without progression to immune disorders during follow up. While using corticosteroids alone, 4/5 patients continued to have recurrent bleeding episodes. All five patients required immunosuppressive therapy for maintenance of a symptom-free period, but survived to a mean follow up of 2 years. CONCLUSIONS: Early definitive diagnosis and aggressive immunosuppressive therapy of IPH are imperative in order to avoid pulmonary fibrosis and mortality in IPH. A chest radiograph should be included in a serial work-up of unexplained anaemia in children. An examination using BAL can confirm IPH and high-resolution thoracic computed tomography scans are useful for early detection of pulmonary fibrosis.
Assuntos
Hemossiderose/fisiopatologia , Pneumopatias/fisiopatologia , Corticosteroides/uso terapêutico , Anemia Ferropriva , Pré-Escolar , Feminino , Hemossiderose/diagnóstico por imagem , Hemossiderose/tratamento farmacológico , Hemossiderose/imunologia , Humanos , Imunossupressores/uso terapêutico , Lactente , Pneumopatias/diagnóstico por imagem , Pneumopatias/tratamento farmacológico , Pneumopatias/imunologia , Masculino , Auditoria Médica , Radiografia , Estudos Retrospectivos , TaiwanRESUMO
Idiopathic pulmonary haemosiderosis is a very rare but devastating disorder. Diagnosis is sometimes difficult and the clinical course exceedingly variable, as illustrated by this report of a girl, aged 2 years 4 months, with severe iron deficiency anaemia. There was no response to iron therapy and transfusions. Sustained and striking reticulocytosis associated with low haptoglobin mimicked haemolytic anaemia. Positive faecal blood test was documented after repeated testing. There were no pulmonary symptoms. A chest radiograph showed bilateral diffuse alveolar infiltrates. Bronchoalveolar lavage fluid showed numerous siderophages. High resolution computed tomography of the thorax revealed early pulmonary fibrotic changes. Recurrent reticulocytosis appeared to be a very useful sign of recurrent bleeding episodes.
Assuntos
Hemossiderose/diagnóstico , Pneumopatias/diagnóstico , Anemia Ferropriva/complicações , Líquido da Lavagem Broncoalveolar/citologia , Pré-Escolar , Feminino , Transtornos Hemorrágicos/etiologia , Hemossiderose/complicações , Humanos , Pneumopatias/complicaçõesRESUMO
A case beta-thalassaemia major complicated with Klebsiella pneumoniae endogenous endophthalmitis is presented to increase physician awareness of the association of the two clinical conditions. Severe morbidity including subretinal abscess and retinal detachment may develop despite aggressive intravenous and intravitreal ceftriaxone therapy, along with vitrectomy and external drainage.
Assuntos
Endoftalmite/microbiologia , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/isolamento & purificação , Mastoidite/microbiologia , Pneumonia Bacteriana/microbiologia , Talassemia beta/complicações , Adolescente , Antibacterianos/administração & dosagem , Feminino , Humanos , Infusões Intravenosas , Infecções por Klebsiella/diagnóstico , Infecções por Klebsiella/tratamento farmacológico , Mastoidite/tratamento farmacológico , Necrose , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/patologia , Prognóstico , Resultado do Tratamento , Talassemia beta/diagnósticoRESUMO
BACKGROUND: To evaluate T helper 1 (Th1)/Th2 cells and cytokines in patients with three different subtypes of juvenile rheumatoid arthritis (JRA). METHODS: Peripheral blood was obtained from 25 children with JRA suffering from active arthritis (8 systemic, 9 pauciarticular and 8 polyarticular). Eight healthy children were recruited as controls. T helper cells from peripheral blood mononuclear cells (PBMC) were evaluated by using intracellular staining analysis of cytokine production with 3-colored flow cytometry. A Th1 cell was defined as an interferon-gamma (IFN-gamma) producing CD4+ cell, and a Th2 cell as an interleukin-4 (IL-4) producing CD4+ cell. The production of IL-2, IL-4, IL-5 and IFN-gamma from PBMC was measured by ELISA. RESULTS: In comparison with normal controls, the patients with JRA had significantly fewer Th2 cells among their PBMC (0.78 +/- 0.56% vs. 5.44 +/- 2.33%, p < 0.001). The percentage of Th1 cells among PBMC was not different between patients and normal controls (4.32 +/- 3.24% vs. 4.52 +/- 2.56%, p > 0.5). The ratio of Th1/Th2 cells in the patient group was significantly higher than the control group (8.38 +/- 8.63 vs. 0.95 +/- 0.66, p < 0.001). After 24-hour culture, the PBMC from JRA patients produced less IL-4 than that of controls (3.61 +/- 0.56 pg/mL vs. 4.29 +/- 0.68 pg/mL, p = 0.002). The production of IL-2, IL-5, and IFN-gamma did not show significant differences between JRA patients and normal controls. CONCLUSION: Decreased IL-4 producing T-helper cells were identified in all three subtypes of JRA. This implicates that an imbalance of Th sub-populations might be a predominant factor in JRA pathogenesis.
Assuntos
Artrite Juvenil/imunologia , Interleucina-4/biossíntese , Células Th1/imunologia , Células Th2/imunologia , Adolescente , Criança , Pré-Escolar , Citocinas/biossíntese , Feminino , Humanos , Masculino , Células Th1/metabolismo , Células Th2/metabolismoRESUMO
Klebsiella pneumoniae has been emerging as the leading cause of liver abscess in diabetic patients. Results of molecular typing of K. pneumoniae isolates from two siblings with liver abscess, their family members, and the environment suggest a possibility of cross infection of liver abscess by the fecal-oral route within diabetic patients.
Assuntos
Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/classificação , Klebsiella pneumoniae/isolamento & purificação , Abscesso Hepático/microbiologia , Núcleo Familiar , Adolescente , Eletroforese em Gel de Campo Pulsado , Feminino , Humanos , Klebsiella pneumoniae/genética , Masculino , Reação em Cadeia da PolimeraseRESUMO
Langerhans cell histiocytosis (LCH) is an enigmatic disease usually occurring in children. Tumor lysis syndrome (TLS) is a clinical syndrome associated with severe metabolic derangement and oliguric acute renal failure. In this report, we present the clinical course of an infant with advanced LCH who had TLS develop after chemotherapy. Treatment with continuous arteriovenous hemofiltration resulted in effective control of serum uric acid, potassium, creatinine, phosphorus, and blood urea nitrogen levels in the blood.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Hemofiltração , Histiocitose de Células de Langerhans/complicações , Doenças Orbitárias/complicações , Osso Temporal/patologia , Síndrome de Lise Tumoral/terapia , Injúria Renal Aguda/etiologia , Alopurinol/uso terapêutico , Biomarcadores , Transfusão de Sangue , Terapia Combinada , Progressão da Doença , Etoposídeo/administração & dosagem , Evolução Fatal , Feminino , Hidratação , Histiocitose de Células de Langerhans/tratamento farmacológico , Humanos , Lactente , L-Lactato Desidrogenase/sangue , Linfonodos/patologia , Mercaptopurina/administração & dosagem , Insuficiência de Múltiplos Órgãos/etiologia , Pescoço , Doenças Orbitárias/tratamento farmacológico , Prednisolona/administração & dosagem , Bicarbonato de Sódio/uso terapêutico , Síndrome de Lise Tumoral/sangue , Síndrome de Lise Tumoral/etiologia , Ácido Úrico/sangue , Vimblastina/administração & dosagem , Vincristina/administração & dosagemAssuntos
Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Aspergilose/complicações , Aspergilose/tratamento farmacológico , Leucemia Mieloide Aguda/complicações , Infecções Oportunistas/complicações , Infecções Oportunistas/tratamento farmacológico , Rinite/complicações , Sinusite/complicações , Adolescente , Antineoplásicos/uso terapêutico , Aspergilose/diagnóstico , Aspergillus/isolamento & purificação , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Infecções Oportunistas/microbiologia , Rinite/tratamento farmacológico , Rinite/microbiologia , Sinusite/tratamento farmacológico , Sinusite/microbiologia , Tomografia Computadorizada por Raios XRESUMO
This double-blind, parallel-group, multicenter study compared the efficacy and safety of intravenous (i.v.) ondansetron with oral syrup ondansetron plus oral dexamethasone in the prevention of nausea and emesis in pediatric patients receiving moderately/highly emetogenic chemotherapy. On each day of chemotherapy, patients were administered ondansetron 5 mg/m2 i.v. and placebo syrup orally (n = 215) or ondansetron 8 mg syrup orally and placebo i.v. (n = 223) plus dexamethasone 2-4 mg p.o. Ondansetron 4 mg syrup p.o. was administered twice daily for 2 days following the cessation of chemotherapy. Complete or major control of emesis was obtained in 89% patients in the i.v. group and 88% patients in the oral syrup group during the worst day of chemotherapy treatment (90% CI: -6, 4) and in 85% and 82% patients, respectively, during the worst day of the study period (90% CI: -8, 3). Intravenous or oral syrup ondansetron plus dexamethasone was well tolerated and effective in preventing chemotherapy-induced emesis in pediatric patients.