ISSN:1077-4114    

出版商:OVID    

年代:1997

数据来源: OVID

ISSN:1077-4114    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

PurposeMitochondrial abnormalities are major causes of human disease. Pearson syndrome illustrates many features of abnormal mitochondrial function and genetics.DesignMitochondria form adenosine triphosphate (ATP) via five multienzyme complexes of the electron transport chain and oxidative phosphorylation, composed from a blend of nuclear and mitochondrial gene products. Mitochondrial DNA (mtDNA) is small (16.6 kb), encoding some subunits of these complexes as well as transfer RNA (tRNA) and ribosomal RNA, but is replicated and transcribed by nuclear encoded polymerases. Multiple copies of mtDNA are passed on to progeny cells via the cytoplasm, accounting for maternal inheritance. Normal and mutant mtDNA can coexist within the same cell (heteroplasmy); when the proportion of mutant mtDNA exceeds a threshold, cellular function is impaired, resulting in disease.Results and ConclusionsMtDNA abnormalities include point mutations, deletions, and depletion. Point mutations in an enzyme subunit cause a specific disorder, whereas point mutations in the tRNAs result in general impairment of protein synthesis and are associated with a variety of disorders. Large mtDNA deletions, initially described in Kearns-Sayre syndrome (KSS), were found soon thereafter in Pearson syndrome. Survivors of Pearson syndrome have gone on to develop KSS. A whole spectrum of disease forms, ranging from isolated sideroblastic anemia to combined Pearson and KSS, are associated with delections of mtDNA. Diagnosis of mitochondrial disorders depends on clinical suspicion, enhanced by evidence of abnormal mitochondrial structure, number, and/or function. Effective treatment for mitochondrial disorders is very limited, including correction of the metabolic milieu, activation of enzyme activity by drugs or cofactors, and removal of reactive oxygen species.

ISSN:1077-4114    

出版商:OVID    

年代:1997

数据来源: OVID

ISSN:1077-4114    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

PurposeA retrospective study was conducted to investigate the relationship between CD44 expression in neuroblastoma and related tumors and other known prognostic indicators.Materials and MethodsImmunostaining of CD44 was done on surgical specimens of 55 cases (42 patients) of neuroblastoma (NB) and ganglioneuroblastoma (GNB) and nine cases of ganglioneuroma. The percentage of positive tumor cells was scored semiquantitatively (0-4+) by two observers. CD44 expression was then correlated with survival, age, stage, and N-myc amplification.ResultsFifty-seven percent of the patients with NB or GNB had heterogeneous positive staining (2-4+) on their diagnostic specimens. Twenty-four percent of the patients had no staining for CD44, and 19% had 1+ staining. In the 17 cases with N-myc analysis, an inverse relationship was demonstrated between N-myc and CD44 expression by univariate analysis. Lack of expression of CD44 was highly associated with poor survival (p= 0.0002). When assessing the joint effects of age, stage, and CD44 in multivariate analysis, the effect of CD44 remains significant (p= 0.028) and appears to be independent of age and stage.ConclusionOur data suggest a relationship between CD44 and N-myc amplification. Absence or low expression of CD44 correlates with poor survival and may be a biologic marker of tumor aggressiveness. CD44 appears to be an independent prognostic marker and deserves continued investigation in prospective studies of neuroblastoma.

ISSN:1077-4114    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

PurposeTo determine the clinical significance of the antinuclear antibody (ANA) test in selected children with idiopathic thrombocytopenic purpura (ITP).MethodsThe study was conducted through retrospective chart review and long-term follow-up by telephone interview.ResultsOf 87 children with ITP who had an ANA performed, 25 had a positive titer (median=1:160, range: 1:40 to 1:2,560). Children with a positive ANA were more likely to be older girls who developed chronic ITP, but there was no correlation with family history of autoimmune disease, initial hemoglobin concentration, or initial platelet count. With an average follow-up of more than 5 years, more children with a positive ANA developed further autoimmune symptoms than those with a negative ANA (36% vs. 0%,p< 0.001). Nine children with a positive ANA developed additional autoimmune symptoms, including five with clinical criteria sufficient for the diagnosis of systemic lupus erythematosus (SLE). Autoantibodies to dsDNA were more prevalent in the children with progression of autoimmune symptoms (57% vs. 0%,p= 0.04). The presence of any autoantibody in addition to the ANA, including dsDNA, SS-A/Ro, SS-B/La, Smith Antigen (Sm), nuclear ribonucleoprotein (nRNP), or cardiolipin was more common in children who had further autoimmune symptoms (75% vs. 0%,p= 0.003).ConclusionsThe ANA is a useful screening test in a subset of children with ITP, especially older girls with chronic ITP, who are at risk for the development of generalized autoimmune disease. Children with ITP and a positive ANA should receive careful follow-up.

ISSN:1077-4114    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

PurposeThe goal was to conduct a phase I/II trial of escalating doses of Idarubicin (Ida) in conjunction with the previously established maximum tolerated dose (MTD) of F-ara-A/ara-C in children with refractory or recurrent acute myeloid leukemia (AML).Patients and MethodsWe conducted a phase I/II trial in parallel with Children's Cancer Group (CCG) study 0922, which involved dose escalation of Ida at levels of 6 mg/m2, 9 mg/m2, and 12 mg/m2over 15 minutes on days 0, 1, and 2. As phase I safety was documented by CCG, we increased the dose of Ida given on day 0, 1, and 2 of the F-ara-A/ ara-C infusion (F-ara-A: 10.5 mg/m2over 15 minutes and 1.27 mg/m2/hour for 48 hours followed by ara-C: 390 mg/m2over 15 minutes and 101 mg/m2/hour for 72 hours).ResultsTen of 15 patients achieved remission. There was one toxic death due to adult respiratory distress syndrome. The median time to an absolute neutrophil count (ANC) > 200/μl was 29 days; ANC > 1,000/μl was 41 days; and platelets > 100,000/μl was 45 days.ConclusionsA dose of 12 mg/m2/day × 3 of Ida did not exceed dose-limiting toxicity with this combination of F-ara-A/ara-C. Substantial activity of this regimen was seen in pediatric patients with AML.

ISSN:1077-4114    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

PurposeTo determine the hematopoietic and nonhematopoietic toxicity of a novel dose-intensive chemotherapy regimen for the treatment of children with relapsed solid tumors.Patients and MethodsThe time to hematopoietic recovery and toxicity experienced during 46 courses of high-dose cyclophosphamide (4.0 g/m2), MESNA, and carboplatin (400 mg/m2) with granulocyte colony stimulating factor (G-CSF) support in 14 children with recurrent solid tumors was reviewed.ResultsAll patients developed grade 4 neutropenia and thrombocytopenia. Recovery to an absolute neutrophil count (ANC) of 500/μl and platelet count of 50,000/μl occurred at a median of 15 days and 23 days respectively. Median time to ANC > 1,000/μl and platelets > 100,000/μl was 27 days. Hospitalization for fever and neutropenia occurred during 35 of 46 courses, with documented bacteremia in six courses. There was no grade II or greater nonhematopoietic organ toxicity. Responses (CR + PR) were observed in 6 of 11 evaluable patients.ConclusionsThese data suggest that this regimen is tolerable in heavily pretreated children with solid tumors with myelosuppression as the primary toxicity. Due to the lack of significant nonhematopoeitic toxicity, this is a good candidate regimen for dose escalation using peripheral blood progenitor cell infusions and deserves further evaluation for efficacy in children with both recurrent and newly diagnosed high-risk solid tumors.

ISSN:1077-4114    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

PurposeTo observe the safety and efficacy of hydroxyurea (HU), a drug that stimulates fetal hemoglobin (Hb F) production, in previously severely ill children with sickle cell disease.Patients and MethodsHU was given in an uncontrolled study to 35 children with sickle cell disease, aged from 3 to 20 years, suffering from frequent painful crises. Mean duration of treatment was 32 months (range: 12-59 months).ResultsHU induced an increase in Hb F levels in all children but one; this increase was maximal after 9 months of treatment, was largely sustained thereafter, and was related to HU dose and inversely to patients' age. We also noted an apparent reduction in crisis, which occurred principally after 3 months of therapy and did not seem strictly correlated with the rise in Hb F level. No serious hematopoietic complication was observed. Growth curves and sexual development were not modified.ConclusionOur data support the efficacy of HU in reducing painful events in children with sickle cell disease. Short- and middle-term tolerances are good. Thus, we think that HU can be given to children affected by frequent and severe painful crises. We recommend, however, very cautious use of this drug, because its long-term effects in children are still unknown.

ISSN:1077-4114    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

PurposeRhabdomyosarcomas (RMS) are heterogeneous in their clinical presentation, histology, and cytogenetics. The growth of some RMS cells has been found to be regulated by the tyrosine kinase insulin-like growth factor (IGF) type I receptor. However, RMS cells exhibit variable sensitivity to inhibitors of tyrosine kinases and IGF receptors. Collectively, these heterogeneous features suggest that differences exist in the growth regulatory pathways of RMS. The objective of this study is to identify active tyrosine kinase signal transduction pathways in embryonal and alveolar RMS cells.MethodsRMS tumor samples and cell lines representing both embryonal and alveolar histologic subtypes have been analyzed by immunoprecipitation and immunoblotting techniques to characterize phosphotyrosyl protein patterns and to identify tyrosine phosphorylated proteins.ResultsRMS cells can be characterized based on the patterns of phosphotyrosyl proteins, including the phosphorylation status of the catenin-like protein Cas 1 and the signal adapter protein SHC, and the activation of IGF type I receptor signaling cascades including the formation of SHC-GRB2 signal protein complexes and MAP kinase activation.ConclusionsRhabdomyosarcomas, especially the embryonal histologic subtype, are heterogeneous at the level of tyrosine kinase signal transduction. It will be important to characterize the growth regulatory pathways active in individual RMS tumors before targeting molecular therapies to this malignancy.

ISSN:1077-4114    

出版商:OVID    

年代:1997

数据来源: OVID