Policy and science in children's health and environment: recommendations from the PINCHE project

BACKGROUND: Policy recommendations result from the discussions and analysis of the present situation in environment and health. Such analysis was performed in PINCHE. This led to recommendations based on the scientific literature. In the field of children's environmental health the policy process will follow more or less fixed rules, but this process is still at an early level of development. The link between science and policy still faces many challenges. Scientific assessment of environmental risk must recognize and tackle the problems of data sets, variability of human and environmental systems, the range, spatial and temporal diffusion of potential health effects and many biases and confounding factors. RESULTS: The PINCHE network recommends a general improvement of the supporting scientific fields in environment and health. Assessments from epidemiology or toxicology should play a key role in influencing science-policy decisions in programmes that are intended to inform the public policy process. Scientific committees at a local level could play a role. The relation between health and environment needs to be better incorporated in training and education. There is a need for harmonization of data production and use. The priorities in PINCHE focus on the most important issues. A classification of low, medium or high priority for action was used to describe a range of different environmental stressors. CONCLUSIONS: PINCHE provided recommendations to reduce exposure for children. Exposure reduction is not always linked to improved health in the short term, but it will reduce the body burden of accumulating chemicals in children. A strategic choice is reduction of exposure of children to compounds by changing production techniques or by increasing the distance of child specific settings to sources. The contribution of all players in the production, distribution and use of scientific knowledge in the field of children's environmental health is necessary.     

Immuno-PET of undifferentiated thyroid carcinoma with radioiodine-labelled antibody cMAb U36: application to antibody tumour uptake studies

Purpose We tested the suitability of the chimeric monoclonal anti-human CD44 splice version 6 antibody (cMAb U36) for targeting and visualising human anaplastic thyroid carcinoma with PET. We also performed experiments aimed at elucidating the relation between tumour interstitial fluid pressure (TIFP) and the tumour uptake of antibodies. Methods The affinity and specificity of the cMAb U36 for KAT-4 cells were evaluated in vitro, as was the Na⁺/I⁻ symporter (NIS) expression. Biodistribution studies were performed on KAT-4 carcinoma-bearing mice injected with ¹²⁴I-cMAb U36 or free iodine. Biodistribution studies were also performed in animals treated with the specific TGF-β1 and -β3 inhibitor Fc:TβRII, which lowers TIFP. Treated and non-treated animals were scanned by microPET. Results Cultured human undifferentiated/anaplastic thyroid carcinoma KAT-4 cells expressed low levels of NIS and uptake of free iodine was insignificant. The cMAb U36 expressed an affinity (K _D) of 11 ± 2 nM. Tumour radioactivity uptake reached maximum values 48 h after injection of ¹²⁴I-cMAb U36 (∼22%IA/g). KAT-4 carcinomas were readily identified in all ¹²⁴I-immuno-PET images. Radioactivity tumour uptake in Fc:TβRII-treated animals was significantly lower at 24 and 48 h after injection, and five times higher thyroid uptake was also noted. Conclusion We successfully used ¹²⁴I-cMAb U36 to visualise CD44v6-expressing human anaplastic thyroid carcinoma. Given the lack of NIS expression in KAT-4, tumour visualisation is not due to free iodine uptake. Lowering the TIFP in KAT-4 carcinomas did not increase the uptake of mAbs into tumour tissue. Alexei V. Salnikov and Marika Nestor contributed equally to this work.     

Accurate diagnosis of acute graft-versus-host disease using serum proteomic pattern analysis

OBJECTIVE: The rapid diagnosis of acute graft-versus-host disease (GVHD) following allogeneic hematopoietic cell transplantation (HCT) is important for optimizing the management of this life-threatening complication. Current diagnostic techniques are time-consuming and require invasive tissue sampling. We investigated serum protein pattern analysis using surface-enhanced laser desorption ionization time-of-flight (SELDI-TOF) mass spectrometry as a tool to diagnose GVHD. PATIENTS AND METHODS: Eighty-eight serum samples were obtained from 34 patients undergoing HCT either pretransplant (n = 28 samples) or at various time points posttransplant (n = 60 samples), including 22 samples obtained on the day of onset of acute GVHD symptoms. Serum proteomic spectra generated from a "training set" of known samples were used to identify distinct proteomic patterns that best categorized a sample as either pretransplant, posttransplant non-GVHD, or GVHD; these distinct proteomic signatures were subsequently used to classify samples from a masked "test" sample set into the appropriate diagnostic category. RESULTS: Proteomic pattern analysis accurately distinguished GVHD samples from both posttransplant non-GVHD samples and pretransplant samples (100% specificity and 100% sensitivity in both cases). Furthermore, distinct serum proteomic signatures were identified that distinguished pretransplant from posttransplant non-GVHD samples (100% specificity and 94% sensitivity). CONCLUSION: These preliminary data suggest a potential application of SELDI-TOF-based proteomic analysis as a rapid and accurate method to diagnose acute GVHD.     

Is the Autism-Spectrum Quotient a Valid Measure of Traits Associated with the Autism Spectrum? A Rasch Validation in Adults with and Without Autism Spectrum Disorders

The Autism-Spectrum Quotient (AQ) is among the most widely used scales assessing autistic traits in the general population. However, some aspects of the AQ are questionable. To test its scale properties, the AQ was translated into Swedish, and data were collected from 349 adults, 130 with autism spectrum disorder (ASD) and 219 without ASD, and analysed with Rasch. Several scale properties of the AQ were satisfactory but it did not meet the criterion of a unidimensional measure of autistic traits. The Rasch analysis showed that the 50-item AQ could be reduced to a 12-item subset with little loss of explanatory power, with the potential to efficiently measure the degree to which adults with and without ASD show autistic traits.     

Perinatal vitamin D levels are not associated with later risk of developing pediatric-onset inflammatory bowel disease: a Danish case-cohort study

Objective Basic and epidemiologic studies on inflammatory bowel disease (IBD) have suggested an association between vitamin D and IBD risk. Though, the literature on IBD – especially pediatric-onset IBD – and vitamin D is still in its cradle. We therefore wanted to examine if levels of 25(OH)D at birth were associated with increased risk of developing pediatric-onset IBD. Material and methods A case-cohort study composed of cases diagnosed with Crohn’s disease, ulcerative colitis or indeterminate/unclassified colitis and healthy controls. Cases and controls were matched on date of birth and were born in the period 1981–2004. Cases were diagnosed before the age of 18 years. The concentration of 25(OH)D was assessed from neonatal dried blood spots using a highly sensitive liquid chromatography tandem mass spectrometry. Odds ratios (OR) were calculated using conditional logistic regression and two-way ANOVA were used to test for season and birth year 25(OH)D variations. A total of 384 matched pairs were included in the statistical analyses. Results No significant association were found between levels of 25(OH)D and IBD risk in the adjusted model (OR [95% CI] (per 25?nmol/L increase), 1.12 [0.88; 1.42], p?=?0.35). 25(OH)D levels were found to fluctuate significantly with season (p?p?Conclusion Our study do not suggest that a window of vulnerability exist around time of birth in regards to 25(OH)D levels and later pediatric-onset IBD risk.     

Outcomes of periradicular surgery in cases with apical pathosis and untreated canals

OBJECTIVE: Surgical management is intended to eliminate or block infection originating in the root canals. The root end is customarily sealed to prevent pathogenic products remaining in the root canal from reaching the periradicular tissues. The purpose of this study was to evaluate the microbiologic and radiographic outcomes of surgical treatment of periradicular pathosis associated with teeth with necrotic pulps. STUDY DESIGN: One tooth from each of 10 patients was root-end resected and root-end filled without prior root canal treatment. One year postoperatively, the outcomes were assessed radiographically and the root canals were sampled for bacteria. RESULTS: Radiographic examination showed complete or incomplete (scar tissue) healing in 5 teeth and uncertain healing in the other 5 teeth. Bacteriologic samples from the root canals were positive in 9 of the 10 cases. CONCLUSIONS: In teeth with necrotic pulps, treatment of periradicular pathosis by surgery and root-end filling may show radiographic evidence of satisfactory healing 1 year postoperatively. However, viable bacteria may persist in the canals, constituting a potential risk factor for recurrence of periradicular pathosis.     

In vitro evaluation of the astatinated chimeric monoclonal antibody U36, a potential candidate for treatment of head and neck squamous cell carcinoma

Purpose The purpose of this study was to analyse the properties of the astatinated chimeric MAb (cMAb) U36 as a conjugate to selectively target and eradicate head and neck squamous cell carcinoma (HNSCC).Methods cMAb U36 was labelled with ²¹¹At via the linker N-succinimidyl 4-(trimethylstannyl)benzoate (SPMB). The quality of the conjugate was extensively evaluated for binding and internalisation capacity, and compared with ¹²⁵I-SPMB-cMAb U36. The cellular toxicity of the astatinated conjugate was assessed in two types of in vitro growth assay and compared with ¹³¹I-labelled cMAb U36 (directly labelled).Results Comparisons between ²¹¹At-cMAb U36 and ¹²⁵I-cMAb U36 demonstrated an optimal functional capacity of the labelled products. Immunoreactivity and affinity assays showed high immunoreactive fractions (>93%), and an affinity in good agreement between the astatinated and iodinated antibodies. For both conjugates, specific binding to HNSCC cells could be demonstrated, as well as some internalisation. Retention of the astatinated conjugate was just slightly lower than for the iodinated conjugate and still reasonable for therapeutic use (31±2% vs 42.6±1.0% at 22 h), demonstrating no adverse effects from astatination of the antibody. Studies on cellular toxicity demonstrated a dose-dependent and antigen-specific cellular toxicity for ²¹¹At-cMAb U36, with about 10% cell survival at 50 decays per cell. The ¹³¹I-labelled conjugate was not as efficient, with a surviving cell fraction of about 50% at 55 decays per cell.Conclusion These results indicate that ²¹¹At-cMAb U36 might be a promising future candidate for eradicating HNSCC micrometastases in vivo.     

Childhood sexual abuse. Women's health when starting in group therapy

Childhood sexual abuse has been shown to be common among adult women, 15-30% in prevalence studies, and among mentally ill women, 25-77%. These women often suffer from depression, anxiety, sexual and relationship problems. Suicide attempts and self-destructive behaviour are common. Within the Department of Psychiatry at Lund University Hospital, 45 women with experiences of childhood sexual abuse were offered a 2-year-long trauma-focused group therapy. They were well educated but 27% were unemployed. Nearly half of the group had made suicide attempts, 87% had had suicidal thoughts and, according to the questionnaire SCL-90, they were suffering from psychiatric symptoms significantly to a greater degree than both a general group and a clinical group with mixed diagnoses. According to the questionnaire ISSI, they were less well socially integrated than both a general group and a clinical group, and the degree of social adjustment according to the questionnaire SAS-SR was lower than in a general group. The study shows that childhood sexually abused women seeking therapy are a symptom-burdened group. These women probably need psychiatric treatment of a particular character. Special group therapy for these women can potentially improve their health.     

Estimation of regional cerebral utilization of [11C]-L-3, 4-dihydroxy-phenylalanine (DOPA) in the primate by positron emission tomography

The intracerebral kinetics of [11C]-labelled L-3,4-dihydroxyphenylalanine, L-DOPA, was investigated in rhesus monkeys by positron emission tomography (PET). Through the labelling of the L-DOPA molecule in different positions and observation of a series of pharmacological challenges it was possible to establish that the kinetic conversion of the radiotracer in the striatum represents the process of decarboxylation to [11C]-labelled dopamine. The rate constant for this process can be estimated using a two-compartment model. The use of [11C]-L-DOPA and PET will thus provide a possibility for in vivo studies of blood-brain barrier transport of the amino acid as well as for the estimation of the ability for brain tissue to decarboxylate the tracer by the action of aromatic L-amino acid decarboxylase.