Type I osteogenesis imperfecta and multiple osteochondromas in the same child.

A male infant showed a humeral diaphysis fracture at 5 months of age and a distal tibial physis fracture at 2 years of age. A specialized consultant ruled out child abuse. This child had the characteristic features of type I osteogenesis imperfecta: blue sclerae, osseous fragility, and presumably autosomal dominant inheritance, as his father suffered from similar disorders. Later on, multiple painful osteochondromas were also found and some of these were surgically treated. The child's mother showed several peripheral osteochondromas. We describe the follow-up of this patient up to the age of 18 years. To our knowledge, the fortuitous association of these two inherited conditions has not been reported in medical literature.

Immunopathogenesis of Asthma and Atopic Diseases – The specific Role of a selected Panel of Genes in human T helper Cell Differentiation

T helper cell (Th) functions are crucial for proper immune defence against various intra- and extracellular pathogens. According to the specific immune responses, Th cells can be classified into subtypes, Th1 and Th2 cells being the most frequently characterized classes. Th1 and Th2 cells interact with other immune cells by regulating their functions with specific cytokine production. IFN, IL-2 and TNF- are the cytokines predominantly produced by Th1 cells whereas Th2 cells produce Th2-type cytokines, such as IL-4, IL-5 and IL-13. Upon TCR activation and in the presence of polarizing cytokines, Th cells differentiate into effector subtypes from a common precursor cell. IFN and IL-12 are the predominant Th1 polarizing cytokines whereas IL-4 directs Th2 polarization. The cytokines mediate their effects through specific receptor signalling. The differentiation process is complex, involving various signalling molecules and routes, as well as functions of the specific transcription factors. The functions of the Th1/Th2 cells are tightly regulated; however, knowledge on human Th cell differentiation is, as yet, fairly poor. The susceptibility for many immune-mediated disorders often originates from disturbed Th cell responses. Thus, research is needed for defining the molecular mechanisms involved in the differentiation and balanced functions of the Th cells. Importantly, the new information obtained will be crucial for a better understanding of the pathogenesis of immune-mediated disorders, such as asthma or autoimmune diseases. In the first subproject of this thesis, the role of genetic polymorphisms in the human STAT6, GATA3 and STAT4 genes were investigated for asthma or atopy susceptibility in Finnish asthma families by association analysis. These genes code for key transcription factors regulating Th cell differentiation. The study resulted in the identification of a GATA3 haplotype that associated with asthma and related traits (high serum IgE level). In the second subproject, an optimized method for human primary T cell transfection and enrichment was established. The method can be utilized for functional studies for the selected genes of interest. The method was also utilized in the third subproject, which aimed at the identification of novel genes involved in early human Th cell polarization (0-48h) using genome-wide oligonucleotide arrays. As a result, numerous genes and ESTs with known or unknown functions were identified in the study. Using an shRNA knockdown approach, a panel of novel IL-4/STAT6 regulated genes were identified in the functional studies of the genes. Moreover, one of the genes, NDFIP2, with a previously uncharacterized role in the human Th differentiation, was observed to promote IFN production of the differentiated Th1 cells. Taken together, the results obtained have revealed potential new relevant candidate genes serving as a basis for further studies characterizing the detailed networks involved in the human Th cell differentiation as well as in the genetic susceptibility of Th-mediated immune disorders.

The Child Occupational Self Assessment (COSA, version 2.1) : lasten toimintamahdollisuuksien itsearviointi COSA:n esittely ja suomentamisprosessi

Tämän opinnäytetyön tarkoituksena on aloittaa lapsille ja nuorille suunnatun The Child Occupational Self Assessment (COSA, version 2.1) itsearviointimenetelmän suomenkielisen version käännöstyö. COSA on asiakaslähtöinen itsearviointi, jolla kartoitetaan lasten ja nuorten kokemusta toiminnallisesta pätevyydestään ja jokapäiväisten toimintojen tärkeydestä heille. COSA pohjaa Inhimillisen toiminnan malliin ja sen toteutus seuraa asiakaslähtöistä teoriaa. COSA:n avulla voidaan asettaa toimintaterapialle tavoitteet ja tarkastella niiden toteutumista. Työssämme suomennamme arviointimenetelmän nimen muotoon; Lasten toimintamahdollisuuksien itsearviointi COSA. Arviointimenetelmän käännöstyö tehdään Helsingin ammattikorkeakoulu Stadian toimintaterapian koulutusohjelmalle. Opinnäytetyössä esittelemme ensin arviointia ja tavoitteiden asettamista lasten toimintaterapiassa sekä itsearvioinnin käyttämistä arviointimenetelmänä. Esittelemme COSA itsearviointimenetelmän sekä sen taustalla vaikuttavat Inhimillisen toiminnan mallin sisällön ja asiakaslähtöisyyden. Kartoitamme myös The Child Occupational Self Assessment (COSA, version 2.1 )itsearviointimenetelmän kehittymistä, sitä edeltäneitä arviointimenetelmiä ja COSA:sta aiemmin tehtyjä tutkimuksia. Opinnäytetyössä suomennamme COSA:n arviointilomakkeen. Arviointilomakkeessa on 25 lasten ja nuorten toiminnallista pätevyyttä ja jokapäiväisten toimintojen tärkeyttä kartoittava väittämää. Suomentamisprosessissa selvitämme COSA:n arviointilomakkeen väittämien suomennosten ymmärrettävyyden onnistumista kahdeksan käyttökokeiluun ja haastatteluun osallistuvan lapsen avulla. Saimme arviointilomakkeen suomentamisprosessiin apua neljältä lasten kanssa työskentelevältä toimintaterapeutilta sekä koulutusohjelmamme koulutuspäälliköltä. Käyttökokeiluiden sekä toimintaterapeuttien palautteiden avulla viimeistelimme suomennetun arviointilomakkeen väittämät. Opinnäytetyön lopuksi pohdimme arviointilomakkeen suomentamisprosessin vaiheita sekä mahdollisia jatkotutkimusehdotuksia. Luovutimme Lasten toimintamahdollisuuksien itsearviointi COSA:n arviointilomakkeen koulutusohjelmamme käyttöön ja mahdollisten jatkotutkimusten kohteeksi.

Cervical nerve root synovial sarcoma in a child with chromosomal (X;18) translocation. Case report and review of the literature.

We report on an 11-year-old female with a history of cervicobrachialgia and progressive weakness of the right arm. Cervical spine MRI showed an enhancing heterogeneous intradural mass occupying the right C6-C7 foramen. She underwent a right C6-C7 foraminotomy with a complete macroscopic removal of the lesion. Pathological examination revealed a synovial sarcoma. Treatment was completed by chemotherapy and proton radiotherapy, and the girl remained free of symptoms for 3 years. After appearance of new symptoms, a local recurrence was confirmed, and despite aggressive treatment with salvage chemotherapy and radiotherapy, the disease progressed beyond medical control, and the child died, 6 years after diagnosis. Early recognition of this rare entity compared to its more benign differential diagnosis is crucial, as an aggressive management is needed.

When is a child with status epilepticus likely to have Dravet syndrome?

PURPOSE: To identify clinical risk factors for Dravet syndrome (DS) in a population of children with status epilepticus (SE). MATERIAL AND METHODS: Children aged between 1 month and 16 years with at least one episode of SE were referred from 6 pediatric neurology centers in Switzerland. SE was defined as a clinical seizure lasting for more than 30min without recovery of normal consciousness. The diagnosis of DS was considered likely in previously healthy patients with seizures of multiple types starting before 1 year and developmental delay on follow-up. The presence of a SCN1A mutation was considered confirmatory for the diagnosis. Data such as gender, age at SE, SE clinical presentation and recurrence, additional seizure types and epilepsy diagnosis were collected. SCN1A analyses were performed in all patients, initially with High Resolution Melting Curve Analysis (HRMCA) and then by direct sequencing on selected samples with an abnormal HRMCA. Clinical and genetic findings were compared between children with DS and those with another diagnosis, and statistical methods were applied for significance analysis. RESULTS: 71 children with SE were included. Ten children had DS, and 61 had another diagnosis. SCN1A mutations were found in 12 of the 71 patients (16.9%; ten with DS, and two with seizures in a Generalized Epilepsy with Febrile Seizures+(GEFS+) context). The median age at first SE was 8 months in patients with DS, and 41 months in those with another epilepsy syndrome (p<0.001). Nine of the 10 DS patients had their initial SE before 18 months. Among the 26 patients aged 18 months or less at initial SE, the risk of DS was significantly increased for patients with two or more episodes (56.3%), as compared with those who had only one episode (0.0%) (p=0.005). CONCLUSION: In a population of children with SE, patients most likely to have DS are those who present their initial SE episode before 18 months, and who present with recurrent SE episodes.

Food allergy: Evaluation of the quality of life in Swiss children

Background: Food allergy in children, an increasingly prevalent disease, significantly affects the quality of life. Its impact can be analyzed by the recently validated French version of the Food Allergy Quality of Life Questionnaire (FAQLQ). Objectives: The aim of our study was to evaluate the quality of life in a small sample of Swiss children with IgE-mediated food allergy. Methods: Information were collected with the questionnaire among 0-12 years old children and their parents during a scheduled allergy visit, and analysed in term of emotional impact, food anxiety and social and food limitations. Patients were divided according to the questionnaire in three age groups: group 1 from 0 to 3 years, group 2 from 4 to 6 years and group 3 from 7 up to 12 years. Results: 30 food allergic patients were included, with a girl/boy ratio of 1:1.14. Median age was 6 years. 56% suffered from or had a history of eczema, 23% of rhino-conjunctivitis, 30% of asthma, and 13% reported a drug allergy. None had insect venom allergy. 57% were known to be allergic to one food, 20% to two foods, 20% to 3 foods and 3% had 3 or more food allergies. Tree nuts (51% of all allergies) as well as eggs (28 %) were the major allergies. Emotional impact had a total score of 1.54 but showed differences between age groups. In group 1 it was lower with 0.23, in group 2 the score was 2.03 and 1.77 in group 3. Food anxiety total score was 1.9; 0.76 in group 1, 2.31 in group 2 and 2.23 in group 3. Social and food limitations showed similar results with a total score of 1.73 and 1.23 in group 1, 2.05 in group 2 and 1.68 for group 3. Conclusion: Food allergy affects the quality of life of Swiss children. Our preliminary results on a small sample are comparable to previously published data. We show that the impact of food allergy on daily life increases when the child starts school and social activities.

Rousseau's Child: Preschoolers Expect Strangers to Favor Prosocial Actions

Modern thinking about human nature is notoriously divided between two contradictory notions: The Hobbesian tradition portrays men as driven by selfish desires, while the Rousseauian tradition recognizes altruistic proclivities as truemotivations to cooperate. We tested preschoolers' predictions about the prosocial or antisocial manner in which people would behave toward each other. Four stories were presented to 3- and 4-year-old children. In each story, the protagonists could either cooperate, act in terms of their own interests, or adopt a behavior unrelated to the ongoing scenario. Children as young as 3 years of age expected the protagonists to behave prosocially - and even more so if the protagonists were female. The results suggest that, even at an early age, children are inclined to adopt a "Rousseau-like" stance rather than a "suspicious" or "pessimistic" Hobbesian stance.

Family Alliance as a Moderator of the Link Between Maternal Postpartum Depression and Child Symptoms Assessed by Both Parents

We investigated the moderating effect of family relationships on the links between maternal postpartum depression and child symptoms in a low-risk community sample of families with 3-month-old infants (n = 57). The level of maternal depression was assessed by the Montgomery-Asberg Depression Rating Scale from a clinical interview, child symptoms by the Symptom Check List completed by both parents, and family relationships by direct observation of father-mother-baby interactions (Lausanne Trilogue Play). Families were categorized as high coordination or low coordination from their overall coordination level throughout the play. Results showed no significant links between maternal depression level and child symptoms reported by both parents. Mothers with a high depressive level in high coordination families tended to report more symptoms in their child than did mothers with lower depressive scores, whereas this link was not found in low coordination families. Prevention perspectives and clinical implications of these results are discussed.

Associations of baroreflex sensitivity, heart rate variability, and initial orthostatic hypotension with prenatal and recent postnatal methylmercury exposure in the Seychelles Child Development Study at age 19 years.

BACKGROUND: A few studies have suggested an association between prenatal exposure to methylmercury and decreased heart rate variability (HRV) related to autonomic heart function, but no study has examined this association using baroreflex sensitivity (BRS). In this study we assessed the distribution of BRS and immediate orthostatic hypotension (IOH) in young Seychellois adults and their associations with exposure to prenatal and recent postnatal methylmercury. METHODS: Subjects in the Seychelles Child Development Study (SCDS) main cohort were evaluated at age 19 years. Non-invasive beat-to-beat blood pressure (BP) monitoring (Finapres, Ohmeda) was performed at rest and during active standing in 95 consecutive subjects. Recent postnatal mercury exposure was measured in subjects' hair at the age of 19 years and prenatal exposure in maternal hair grown during pregnancy. BRS was estimated by sequence analysis to identify spontaneous ascending and descending BP ramps. HRV was estimated by the following markers: PNN50 (relative numbers of normal-to-normal intervals which are shorter by more than 50 ms than the immediately following normal-to-normal intervals); rMSSD (root mean of the squared sum of successive interval differences); LF/HF (low frequency/high frequency component ratio); ratio of the mean expiratory/inspiratory RR intervals (EI ratio); and the ratio between the longest RR interval 30 s after active standing and the shortest RR interval at 15 s (Max30/Min15). IOH was estimated by the deepest BP fall within the first 15 s after active standing up. RESULTS: Prenatal MeHg exposures were similar in boys and girls (6.7±4.3, 6.7±3.8 ng/g) but recent postnatal mercury levels were higher in males than females (11.2±5.8 vs 7.9±4.3 ng/g, p=0.003). Markers of autonomic heart rate control were within the normal range (BRS: 24.8±7 ms/mm Hg, PNN50: 24.9±6.8%, rMSSD: 68±22, LF/HF: 0.61±0.28) in both sexes. After standing, 51.4% of subjects had a transient systolic BP drop>40 mm Hg, but only 5.3% reported dizziness or had syncope. Prenatal and recent postnatal MeHg levels, overall, were not associated with BRS, E/I ratio, PNN50, rMSSD, LF/HF ratio, Max30/Min15 ratio, and IOH. CONCLUSIONS: This study provides no support for the hypothesis that prenatal or recent postnatal MeHg exposure from fish consumption is associated with impaired autonomic heart rate control.

The prevalence of child sexual abuse in community and student samples: A meta-analysis

Background: Studies conducted internationally confirm that child sexual abuse is a much more widespread problem than previously thought, with even the lowest prevalence rates including a large number of victims that need to be taken into account. Objective: To carry out a meta-analysis of the prevalence of child sexual abuse in order to establish an overall international figure. Methods: Studies were retrieved from various electronic databases. The measure of interest was the prevalence of abuse reported in each article, these values being combined via a random effects model. A detailed analysis was conducted of the effects of various moderator variables. Results: Sixty-five articles covering 22 countries were included. The analysis showed that 7.9% of men (7.4% without outliers) and 19.7% of women (19.2% without outliers) had suffered some form of sexual abuse prior to the age of eighteen. Conclusions: The results of the present meta-analysis indicate that child sexual abuse is a serious problem in the countries analysed.