Intraocular relapse of childhood acute lymphoblastic leukaemia

Relapse of childhood acute lymphoblastic leukaemia (ALL) involving the eye is a rare but challenging problem. Twenty cases occurred in patients treated on the Medical Research Council United Kingdom Acute Lymphoblastic Leukaemia XI and ALL97 trials between 1991 and 2001, representing 2.2% of ALL relapses. Seventeen occurred as a first relapse, either in isolation or combined with relapse at another site, and three occurred as a second relapse. All patients with intraocular disease at first relapse were treated with both chemotherapy and radiotherapy, but the doses and protocols used varied. Eleven of these 17 patients are alive and in complete remission with a median follow up of 4 years 2 months from relapse. All 11 children that were treated with a full chemotherapy relapse protocol, together with local radiotherapy have survived. Patients treated with chemotherapy of shorter duration and intensity, despite radiotherapy and/or bone marrow transplantation, did poorly with only one survivor, currently in chronic relapse. Consequently, we suggest that children with eye relapse of ALL be treated with an intensive relapse chemotherapy protocol with local ocular radiotherapy, whether the relapse occurs in isolation or in combination with relapse at another site.     

Endocrine and cardiovascular late effects among adult survivors of childhood brain tumors: Childhood Cancer Survivor Study

BACKGROUND: Survivors of childhood brain tumors (CBTs) are at high risk for a variety of late adverse effects. Most research on long-term effects of CBTs has been comprised of single-institution case series without comparison groups. Research on CBT late effects often is focused on neurologic and sensory outcomes, with less emphasis on other potential targets such as the endocrine and circulatory systems. The current study was conducted to contrast the incidence of endocrine and cardiovascular conditions among CBT survivors as a function of treatment and to determine the risk of occurrence of these conditions relative to a sibling comparison group. METHODS: As part of the Childhood Cancer Survivor Study (CCSS), treatment data were collected from medical records and self-reported late effects were ascertained from a survey questionnaire of 1,607 CBT patients who survived their disease for 5 or more years. For comparison purposes, questionnaire data were also collected from 3418 randomly selected siblings of participants in CCSS. RESULTS: One or more endocrine conditions were reported by 43% of CBT survivors. Compared with siblings, CBT survivors had a significantly increased risk of late-onset (>/= 5 years postdiagnosis) hypothyroidism (relative risk [RR] = 14.3; 95% confidence interval [95% CI] 9.7-21.0), growth hormone deficiency (RR = 277.8; 95% CI 111.1-694.9), the need for medications to induce puberty (RR = 86.1; 95% CI 31.1-238.2), and osteoporosis (RR = 24.7; 95% CI 9.9-61.4). One or more cardiovascular conditions were reported by 18% of CBT survivors, with an elevated late-onset risk for stroke (RR = 42.8; 95% CI 16.7-109.8), blood clots (RR = 5.7; 95% CI 3.2-10.0), and angina-like symptoms (RR = 2.0; 95% CI 1.5-2.7). Very few late effects were evident among those treated with surgery only, but risks were consistently elevated for those treated with radiation and surgery, and higher still for those who also received adjuvant chemotherapy. CONCLUSIONS: Childhood brain tumor survivors are at a significantly increased risk for several adverse endocrine and cardiovascular late effects, particularly if they were treated with radiation and chemotherapy. Lifetime medical surveillance and follow-up for potential toxicities are necessary because treatment-related complications may occur many years after therapy.     

Drinks consumed by 18-month-old children: are current recommendations being followed?

OBJECTIVE: To examine the types of drinks consumed by children at 18 months of age, determine any associations with socio-demographic characteristics and investigate the use of a bottle for providing these drinks. DESIGN: A total of 1026 randomly chosen children from the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC) were studied. METHODS: As part of a dietary diary completed when their children were 18 months of age, mothers were asked to record all drinks consumed over a 24 h period and to report the containers used to give these drinks. Socio-demographic characteristics were obtained via self-completion questionnaire. RESULTS: Dietary records were available for 1026 children at 18 months. A wide variety of drinks were given at this age. In all, 64% of children had received at least one drink in a bottle and 10% solely used a bottle. Bottle users consumed a significantly greater volume of milk drinks compared to those who used a cup or other container. The types of drinks consumed and adherence to the guidelines on weaning were associated with several socio-demographic characteristics. In particular, children with mothers of lower educational level were more likely to receive fizzy drinks and low-calorie soft drinks, more likely to drink from a bottle, and less likely to drink from a cup. CONCLUSION: We have shown that certain groups of mothers with 18-month-old children are not following the current guidelines on weaning. Assuming these guidelines have scientific validity, it is clear that nutritional education needs to be targeted at these mothers to help them feed their children in the optimal way, to protect from nutritional deficiencies, possible later obesity and poor dental health. SPONSORSHIP: University of Bristol.     

Immunoglobulins in children with epilepsy: the Dutch Study of Epilepsy in Childhood

In an unselected cohort of 282 children, serum immunoglobulin (Ig) concentrations were determined shortly after the first presentation with one or more unprovoked epileptic seizures and before the start of treatment with anti-epileptic drugs (AEDs), and after 9-18 months of AEDs use. At intake, IgA, IgG1, IgG2 and IgG4 concentrations were significantly higher than published reference values in healthy age-matched controls. In a subset of 127 children, Ig levels at intake were compared with those after AEDs use for 9-18 months. IgA and IgG4 levels had decreased significantly to normal concentrations, but IgG1 and IgG3 levels increased significantly. To determine the influence of AEDs, Ig levels in children who used carbamazepine or valproic acid monotherapy were analysed separately. The use of carbamazepine was associated with a significant decrease of IgA and IgG4 levels, and the use of valproic acid with a significant decrease of IgA and increase of IgG1 levels. In conclusion, humoral immunity is already altered in children shortly after the first presentation with epileptic seizures. Whether this is the consequence of an exogenous event, and to what extent this is related to an interaction of the central nervous system and the immune system, remains to be evaluated. Treatment with AEDs, such as carbamazepine and valproic acid, is associated with significant changes of Ig (sub)class concentrations.     

Is mortalin a candidate gene for T1DM ?

Mortalin has been found to be up-regulated by 2D-protein gel analysis in isolated rodent islets exposed to cytokines. In islets from two rat strains with different sensitivity to the toxic effects of cytokines we observed a significant difference in IL-1beta mediated mortalin expression. Constitutive over-expression of rat mortalin in NIH3T3 cells reduced cellular survival in accordance with mortalin being associated to cellular senescence. Hence we consider the gene encoding for mortalin at chromosome 5q31.1 a putative candidate gene in cytokine induced beta-cell destruction. We scanned the human mortalin gene for polymorphisms and identified three novel polymorphisms. Neither the SNPs individually nor as constructed haplotypes showed disease association tested by (E)TDT in a Danish type 1 diabetes (T1DM) population. Furthermore, we tested the D5S500 microsatelite located close to 5q31.1 without finding linkage to (T1DM). In conclusion, the functional data identifying a difference in mortalin expression in IL-1beta stimulated islets between two rat strains and over-expression of mortalin in NIH3T3 cells associated with decreased viability suggests a functional role for mortalin in cytokine mediated beta cell destruction; however, the identified polymorphisms did not reveal any association in the presence of linkage disequilibrium of mortalin to T1DM in the Danish population.     

全国0～6 岁儿童单纯性肥胖流行病学研究

目的 本研究旨在了解自1996年第二次全国儿童期单纯肥胖症流行学研究后10年来我国儿童期单纯肥胖症的发展特征和趋势;复核本工作组研究初期所确定的工作假设和所选择的指示参数的科学效应;修订本工作组所制定的中国儿童单纯肥胖症控制方案的科学性和可操作性.方法 选择沈阳、济南、青岛、郑州、长沙、重庆、西安、成都、深圳、海口、文昌11个城市,采取随机整群抽样的方法,共调查0～6岁儿童84 766名,代表人口1 414 220名儿童.儿童肥胖的判定标准为世界卫生组织(WHO)身高标准体重值,采用标准差计分法(Z-score),体重高于中位数1个标准差为超重、高于2个标准差为肥胖.测量体重、身长/身高、3岁以上儿童的腰围、臀围、大腿围及血压.计数、计量数据分别采用χ2检验和t检验进行分析,显著性检验水平为0.05.结果 (1)本次调查0～6 岁儿童肥胖、超重总检出率分别为7.2%、19.8%,其中男童肥胖、超重检出率分别为8.9%、22.2%,女童肥胖、超重检出率分别为5.3%、17.0%.较1996年分别增长了3.6、4.7倍,年均增长速度分别为156%和52%.肥胖、超重检出率北部高于西部,中南部居中;男童高于女童.肥胖、超重比仍处于高危水平.(2)出生后1个月儿童的平均体块指数(BMI)值＞16.5,于1个月时BMI均值达最高(17.8),之后逐渐降低,5.5岁时降至最低点(平均值15.7),然后随年龄上升,但最高BMI均值未超过18.(3)本次调查中,脂肪重聚年龄为5.5岁,较1996年后移半年.出生后前半年的脂肪重聚比(ARR1)为0.56,出生后半年(ARR2)为0.97,均处于可接受水平,且明显低于10年前的水平.(4)西部地区儿童由于身高不足,可以出现"假性超重".这既掩盖了早期线性生长不足和营养不良,又掩盖了可能产生的肥胖.(5)本次调查肥胖儿童血压高于第95百分位数的比例高达12.9%,其腰臀比大于本工作组设置的1.0的危险警戒水平者占17.2%.(6)本工作组所设立的BMI参照值及肥胖筛查界值点、脂肪重聚比/年龄等参照值及界值点、腰臀比参照值及界值点等指示参数在现场筛查和指示健康危险因素等方面是适宜、科学、实用的.结论 近10年儿童期单纯肥胖症检出率和肥胖儿童高血压率增加明显,且存在心血管高危状态,应加强儿童期单纯肥胖症的早期预防控制.     

Prognostic Limitations of the Daumas-Duport Grading Scheme in Infratentorial Neuroglial Tumors in Children

The Daumas-Duport grading scheme (DDGS) utilizes four histologic features in an additive method (grade 1 if none present, grade 2 if only one is present, etc.). Its efficacy in achieving prognostically homogeneous groups of childhood infratentorial neuroglial tumors and its concordance with World Health Organization (WHO) diagnoses has not been evaluated. We investigated these questions using the Childhood Brain Tumor Consortium (CBTC) database of 1241 neuroglial tumors limited to the infratentorial compartment. We calculated survival function estimates for various DDGS grades as well as the histologic features within each grade. The feature of endothelial prominence improved survival expectation, whereas the remaining three features of nuclear atypia, mitoses, and necrosis were associated with worsened survival. Survival estimates for tumors with DDGS grades 2 and 3 did not differ. Some grades contained feature subsets with significantly different survival distributions. The survival distributions of DDGS grade 1, DDGS grade 2 with only endothelial prominence, and DDGS grade 3 with nuclear atypia and endothelial prominence were not significantly different. DDGS grade within WHO diagnoses had no significant effect on survival expectation. We conclude that grading by summation of only four histologic features, as in the DDGS, is inappropriate for assessment of childhood neuroglial tumors. A classification scheme considering the complete histologic content is more likely to provide clinically useful diagnoses. Such a scheme, based on the CBTC database is available. This scheme uses 26 histologic features identified as reliable in read–reread studies.See Appendix.     

IAP National Task Force for Childhood Prevention of Adult Diseases: insulin resistance and Type 2 diabetes mellitus in childhood

Type 2 diabetes mellitus (DM) has traditionally been considered a disease of adults. However, in the last 2 decades, it is increasingly being reported in children and adolescents. Obesity is a strong correlate, and the increasing prevalence of obesity and poor physical activity is precipitating type 2 DM at younger ages in the ethnic groups at risk.Indians and other South Asians are among the ethnic groups particularly prone to insulin resistance and type 2 DM, the other racial groups being some American Indian tribes like the Pima Indians, Mexican Americans,Pacific Islanders and African Americans,among others. The WHO has predicted that India will have the greatest number of diabetic individuals in the world by the year 2025.Type 2 DM starting during adolescence puts the individual at risk for major morbidity and even mortality right during the productive years of life. The microvascular complications of DM (nephropathy, retinopathy, neuropathy) are brought on at an early age. In addition, type 2 DM and obesity are two components of a metabolic syndrome of insulin resistance, the other features of which include hypertension, dyslipidemia and hypercoagulability of blood. All these conditions together increase the risk for cardiovascular and cerebrovascular mortality and morbidity (i.e., myocardial infarction and stroke). The resulting economic burden will be enormous.Type 2 DM and the insulin resistance syndrome are to a large extent preventable.Adoption of a healthy eating and physical activity pattern has resulted in decreasing the development of DM in a few recent studies from various parts of the world. A concerted,multi-pronged effort is needed, involving the general public, pediatricians and general physicians, teachers and schools, the media,the government and professional medical bodies, to generate a momentum towards the goal of prevention of type 2 DM and the insulin resistance syndrome in the young population of India.