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81.
Hara J Park YD Yoshioka A Yumura-Yagi K Koudera U Hosoi G Sako M Kosaka Y Sano K Misu H Mabuchi O Aoyagi N Yamamoto M Tawa A Miyata H Tanaka H Kikkawa M Shimodera M Kawa-Ha K;Osaka Childhood Leukemia Study Group 《International journal of hematology》2001,74(2):165-172
Between April 1994 and March 1997, 143 children (age range, 1-15 years) with newly diagnosed acute lymphoblastic leukemia (ALL), except for those patients with t(9;22), were treated according to protocol-94 of the Osaka Childhood Leukemia Study Group. In this trial, the intensity of chemotherapy was enforced in the consolidation and reinduction phases by introducing AML-type block therapies consisting of concentrated administration of 4 to 6 drugs during 5 or 6 days. For patients in the higher risk groups, rotational combination chemotherapy was introduced following the early phase. A total of 124 children with B-cell precursor ALL (B-pre ALL) were classified into 3 groups, the ultrahigh-risk group (UHRG) (15 patients), the high-risk group (HRG) (61 patients), or the standard-risk group (SRG) (48 patients), based on age. leukocyte count, immunophenotype, central nervous system leukemia, response to treatment, and selected chromosomal abnormalities. The complete remission rate was 93%, and the 6-year event-free survival (EFS) rate was 79%+/-4%. EFS rates for the UHRG, HRG, and SRG groups were 67%+/-12%, 80%+/-6%, and 81%+/-6%, respectively. Nineteen patients with T-cell ALL were treated with the protocol for the UHRG. Thirteen patients (68%) attained complete remission, and the 6-year EFS rate was 55%+/-12%. Thus, intensification of chemotherapy improved the EFS rate and AML-type block therapies appeared to be effective as the consolidation and reinduction therapies for B-pre ALL. 相似文献
82.
Sakai M Shirahata A Akatsuka J Fujisawa K Ohkawa H Konishi S Bessho F Miyazaki S;Japanese Childhood Idiopathic Thrombocytopenic Purpura Study Group 《[Rinshō ketsueki] The Japanese journal of clinical hematology》2002,43(9):821-827
Three antiphospholipid antibodies (aPLs), namely, antiphosphatidylinositol antibody (antiinositol antibody), antiphosphatidylserine antibody (antiserine antibody), and anticardiolipin. beta 2-glycoprotein I complex antibody (antiCL. beta 2-GPI antibody), were determined in 49 children with idiopathic thrombocytopenic purpura (ITP) consisting of 14 newly-diagnosed cases and 35 chronic cases. Determination of aPL was performed twice in the newly-diagnosed patients, once each during the acute and convalescent phases, and once in the chronic patients. The positive rates in the acute and convalescent phases of the newly-diagnosed group and in the chronic group were, respectively, 14.3%, 28.6%, and 18.8% for the antiinositol antibody, 14.3%, 14.3%, and 15.6% for the antiserine antibody, and 21.4%, 28.6%, and 25.0% for either of these 2 antibodies. Thus, antiinositol and antiserine aPLs were present at high incidences; however, all patients were negative for the antiCL. beta 2-GPI antibody. No correlation was noted between either the antiinositol or the antiserine antibody and peripheral platelet count, anti-GP IIb/IIIa antibody or PAIgG. Thus, although some aPLs are present in both acute and chronic pediatric ITP, the aPLs seems to be of an infectious disease type. No results that suggest possible involvement of aPLs in ITP pathology were obtained. 相似文献
83.
Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and risk of molecularly defined subtypes of childhood acute leukemia 总被引:16,自引:0,他引:16
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Wiemels JL Smith RN Taylor GM Eden OB Alexander FE Greaves MF;United Kingdom Childhood Cancer Study investigators 《Proceedings of the National Academy of Sciences of the United States of America》2001,98(7):4004-4009
Low folate intake as well as alterations in folate metabolism as a result of polymorphisms in the enzyme methylenetetrahydrofolate reductase (MTHFR) have been associated with an increased incidence of neural tube defects, vascular disease, and some cancers. Polymorphic variants of MTHFR lead to enhanced thymidine pools and better quality DNA synthesis that could afford some protection from the development of leukemias, particularly those with translocations. We now report associations of MTHFR polymorphisms in three subgroups of pediatric leukemias: infant lymphoblastic or myeloblastic leukemias with MLL rearrangements and childhood lymphoblastic leukemias with either TEL-AML1 fusions or hyperdiploid karyotypes. Pediatric leukemia patients (n = 253 total) and healthy newborn controls (n = 200) were genotyped for MTHFR polymorphisms at nucleotides 677 (C-->T) and 1,298 (A-->C). A significant association for carriers of C677T was demonstrated for leukemias with MLL translocations (MLL+, n = 37) when compared with controls [adjusted odd ratios (OR) = 0.36 with a 95% confidence interval (CI) of 0.15-0.85; P = 0.017]. This protective effect was not evident for A1298C alleles (OR = 1.14). In contrast, associations for A1298C homozygotes (CC; OR = 0.26 with a 95% CI of 0.07--0.81) and C677T homozygotes (TT; OR = 0.49 with a 95% CI of 0.20--1.17) were observed for hyperdiploid leukemias (n = 138). No significant associations were evident for either polymorphism with TEL-AML1+ leukemias (n = 78). These differences in allelic associations may point to discrete attributes of the two alleles in their ability to alter folate and one-carbon metabolite pools and impact after DNA synthesis and methylation pathways, but should be viewed cautiously pending larger follow-up studies. The data provide evidence that molecularly defined subgroups of pediatric leukemias have different etiologies and also suggest a role of folate in the development of childhood leukemia. 相似文献
84.
85.
The incidence of Type I diabetes has not increased but shifted to a younger age at diagnosis in the 0-34 years group in Sweden 1983-1998 总被引:1,自引:0,他引:1
Pundziute-Lyckå A Dahlquist G Nyström L Arnqvist H Björk E Blohmé G Bolinder J Eriksson JW Sundkvist G Ostman J;Swedish Childhood Diabetes Study Group 《Diabetologia》2002,45(6):783-791
AIMS/HYPOTHESIS: To analyse the incidence of Type I (insulin-dependent) diabetes mellitus in the 0-34 years age group in Sweden 1983-1998. METHODS: Incidence and cumulative incidence per 100 000 and Poisson regression analysis of age-period effects was carried out using 11 751 cases from two nation-wide prospective registers. RESULTS: Incidence (95%-CI) was 21.4 (20.8-21.9) in men and 17.1 (16.6-17.5) in women between 0 and 34 years of age. In boys aged 0-14 and girls aged 0-12 years the incidence increased over time, but it tended to decrease at older age groups, especially in men. Average cumulative incidence at 35 years was 748 in men and 598 in women. Cumulative incidence in men was rather stable during four 4-year periods (736, 732, 762, 756), while in women it varied more (592, 542, 617, 631). In males aged 0-34 years, the incidence did not vary between the 4-year periods ( p=0.63), but time changes among the 3-year age groups differed ( p<0.001). In females the incidence between the periods varied ( p<0.001), being lower in 1987-1990 compared to 1983-1986, but time changes in the age groups did not differ ( p=0.08). For both sexes median age at diagnosis was higher in 1983-1986 than in 1995-1998 ( p<0.001) (15.0 and 12.5 years in males; 11.9 and 10.4 in females, respectively). CONCLUSION/INTERPRETATION: During a 16-year period the incidence of Type I diabetes did not increase in the 0-34 years age group in Sweden, while median age at diagnosis decreased. A shift to younger age at diagnosis seems to explain the increasing incidence of childhood Type I diabetes. 相似文献
86.
87.
Mona Shah Gulnara Mamyrova Ira N. Targoff Adam M. Huber James D. Malley Madeline Murguia Rice Frederick W. Miller Lisa G. Rider with the Childhood Myositis Heterogeneity Collaborative Study Group?? 《Medicine》2013,92(1)
The juvenile idiopathic inflammatory myopathies (JIIM) are systemic autoimmune diseases characterized by skeletal muscle weakness, characteristic rashes, and other systemic features. Although juvenile dermatomyositis (JDM), the most common form of JIIM, has been well studied, the other major clinical subgroups of JIIM, including juvenile polymyositis (JPM) and juvenile myositis overlapping with another autoimmune or connective tissue disease (JCTM), have not been well characterized, and their similarity to the adult clinical subgroups is unknown. We enrolled 436 patients with JIIM, including 354 classified as JDM, 33 as JPM, and 49 as JCTM, in a nationwide registry study. The aim of the study was to compare demographics; clinical features; laboratory measures, including myositis autoantibodies; and outcomes among these clinical subgroups, as well as with published data on adult patients with idiopathic inflammatory myopathies (IIM) enrolled in a separate natural history study.We used random forest classification and logistic regression modeling to compare clinical subgroups, following univariate analysis. JDM was characterized by typical rashes, including Gottron papules, heliotrope rash, malar rash, periungual capillary changes, and other photosensitive and vasculopathic skin rashes. JPM was characterized by more severe weakness, higher creatine kinase levels, falling episodes, and more frequent cardiac disease. JCTM had more frequent interstitial lung disease, Raynaud phenomenon, arthralgia, and malar rash. Differences in autoantibody frequency were also evident, with anti-p155/140, anti-MJ, and anti-Mi-2 seen more frequently in patients with JDM, anti-signal recognition particle and anti-Jo-1 in JPM, and anti-U1-RNP, PM-Scl, and other myositis-associated autoantibodies more commonly present in JCTM. Mortality was highest in patients with JCTM, whereas hospitalizations and wheelchair use were highest in JPM patients. Several demographic and clinical features were shared between juvenile and adult IIM subgroups. However, JDM and JPM patients had a lower frequency of interstitial lung disease, Raynaud phenomenon, “mechanic’s hands” and carpal tunnel syndrome, and lower mortality than their adult counterparts. We conclude that juvenile myositis is a heterogeneous group of illnesses with distinct clinical subgroups, defined by varying clinical and demographic characteristics, laboratory features, and outcomes. 相似文献
88.
Moorman AV Richards SM Robinson HM Strefford JC Gibson BE Kinsey SE Eden TO Vora AJ Mitchell CD Harrison CJ;UK Medical Research Council 《Blood》2007,109(6):2327-2330
Patients with acute lymphoblastic leukemia (ALL) and an intrachromosomal amplification of chromosome 21 (iAMP21) comprise a novel and distinct biological subgroup. We prospectively screened 1630 (84%) patients treated on the UK MRC ALL97 protocol for iAMP21 and herein present demographic, clinical, and survival data on the 28 (2%) children found to harbor this abnormality. They had a common or pre-B ALL immunophenotype, were significantly older (median 9 years vs 5 years), and had a lower white cell count (median 3.9 vs 12.4) compared with children without this abnormality. Notably, patients with iAMP21 had a significantly inferior event-free and overall survival at 5 years compared with other patients: 29% (95% confidence interval [CI], 13%-48%) versus 78% (95% CI, 76%-80%) and 71% (95% CI, 51%-84%) versus 87% (95% CI, 85%-88%), respectively. As a result of this 3-fold increase in relapse risk, newly diagnosed patients with iAMP21 recruited to the current UK MRC ALL2003 trial are being treated on the high-risk arm and are considered for bone marrow transplantation in first remission. 相似文献
89.
Pörksen S Nielsen LB Kaas A Kocova M Chiarelli F Orskov C Holst JJ Ploug KB Hougaard P Hansen L Mortensen HB;Hvidøre Study Group on Childhood Diabetes 《The Journal of clinical endocrinology and metabolism》2007,92(8):2910-2916
CONTEXT: The role of glucagon in hyperglycemia in type 1 diabetes is unresolved, and in vitro studies suggest that increasing blood glucose might stimulate glucagon secretion. OBJECTIVE: Our objective was to investigate the relationship between postprandial glucose and glucagon level during the first 12 months after diagnosis of childhood type 1 diabetes. DESIGN: We conducted a prospective, noninterventional, 12-month follow-up study conducted in 22 centers in 18 countries. PATIENTS: Patients included 257 children and adolescents less than 16 yr old with newly diagnosed type 1 diabetes; 204 completed the 12-month follow-up. SETTING: The study was conducted at pediatric outpatient clinics. MAIN OUTCOME MEASURES: We assessed residual beta-cell function (C-peptide), glycosylated hemoglobin (HbA(1c)), blood glucose, glucagon, and glucagon-like peptide-1 (GLP-1) release in response to a 90-min meal stimulation (Boost) at 1, 6, and 12 months after diagnosis. RESULTS: Compound symmetric repeated-measurements models including all three visits showed that postprandial glucagon increased by 17% during follow-up (P = 0.001). Glucagon levels were highly associated with postprandial blood glucose levels because a 10 mmol/liter increase in blood glucose corresponded to a 20% increase in glucagon release (P = 0.0003). Glucagon levels were also associated with GLP-1 release because a 10% increase in GLP-1 corresponded to a 2% increase in glucagon release (P = 0.0003). Glucagon levels were not associated (coefficient -0.21, P = 0.07) with HbA(1c), adjusted for insulin dose. Immunohistochemical staining confirmed the presence of Kir6.2/SUR1 in human alpha-cells. CONCLUSION: Our study supports the recent in vitro data showing a stimulation of glucagon secretion by high glucose levels. Postprandial glucagon levels were not associated with HbA(1c), adjusted for insulin dose, during the first year after onset of childhood type 1 diabetes. 相似文献
90.
Marshall NS Almqvist C Grunstein RR Marks GB;Childhood Asthma Prevention Study 《Pediatric pulmonology》2007,42(7):584-591
Snoring is often found in allergic diseases and may be an early manifestation of more serious sleep-disordered breathing. We aimed to investigate whether the risk factors for snoring among pre-school children with rhinitis are similar to those for allergic diseases in a birth cohort. The study cohort was drawn from participants in the Childhood Asthma Prevention Study (CAPS). This is a randomized controlled trial of dietary intervention and house dust mite avoidance during the first 5 years of life, aimed at reducing the risk of acquiring asthma and other allergic conditions in children at high-risk for allergic diseases. Parents of children with symptoms of rhinitis at age 5 years (n = 219 out of 516 cohort members) were asked if their child snored: 127 (60%) reported some snoring and 56 (26%) snored more than three times per week. Multiple logistic regression analyses indicated that children who were first-born (adjusted odds ratio, 2.50, 95% CI 1.20-5.21), were exposed to maternal tobacco smoke during the first year of life (2.40, 1.1-5.25), or who had asthma (2.51, 1.14-5.55) and/or eczema (2.29, 1.02-5.13) at age 5 years were more likely to snore. Birth-weight, body mass index at age 4.5, spirometry, and breastfeeding were not related to snoring. Risk factors for snoring are similar to risk factors for allergic disorders. Snoring may be part of the allergic spectrum of diseases. Our data may contribute to clinician's ability to effectively screen for snoring in preschool children. 相似文献