Intranasal treatment of vitamin B12 deficiency in children.

Vitamin B12 deficiency is traditionally treated with intramuscular injections of cobalamin, which are stressful events for children. In adults, studies have shown adequate absorption of intranasally administered vitamin B12. To date, data concerning efficacy of intranasal administration of vitamin B12 in children are lacking. We report on ten cases of children with vitamin B12 deficiency who were successfully treated with intranasal administration of a spray containing hydroxocobalamin. The mean baseline vitamin B12 concentration increased from 126.3 pmol/l (SD 55.4) to 1914.7 pmol/l (SD 1509.7). No side effects were reported.Conclusion: In children, intranasal application of vitamin B12 seems a safe and effective alternative to intramuscular injections, leading to higher compliance and less burden to patients.What is Known:• Children with vitamin B12deficiency are traditionally treated with intramuscular cobalamin injections, which are costly and painful.• Studies in adults showed that intranasal application of hydroxocobalamin leads to normalisation of vitamin B12levels.What is New:• The intranasal application of vitamin B12resulted in a substantial increase of the mean baseline vitamin B12levels without any side effect.• These data encourage a systematic evaluation of intranasal treatment of vitamin B12deficiency in order to define safety, optimal dosage and administration frequency.

A twin-sibling study on early growth and hormone levels in adolescents.

This study addresses how growth during sensitive developmental periods and genes may affect hormone levels in late adolescence. We analyzed hormone levels of dehydroepiandrosterone sulfate (DHEAS) and insulin-like growth factor-I (IGF-I), which are hypothesized to be two pathways linking early growth with adult diseases (such as type 2 diabetes and cardiovascular disease) via their effects on enhanced insulin resistance. In a twin-sibling study, we tested whether there is an association between reduced intra-uterine growth and higher DHEAS or IGF-I levels in serum during adolescence, and we examined the contribution of insulin to the link between early growth and higher DHEAS and/or IGF-I levels. Anthropometric and hormone data were collected in 18-year-old twins (184 pairs) and their non-twin siblings (n = 98). Neither birth weight nor current body size predicted serum DHEAS and IGF-I levels. In the subsample of children who showed catch-up growth in weight during infancy, the children of lower birth weight had significantly higher serum DHEAS and IGF-I levels, but these were not related to insulin levels. Variation in serum DHEAS, IGF-I and fasting insulin levels was largely explained by genetic factors (73, 78 and 61 % respectively). Thus, early growth affects hormone levels in adolescence, but only in children with catch-up growth after birth. No evidence was found that early growth enhances insulin resistance via the hormones DHEAS or IGF-I.

[Definition, diagnosis and therapy of chronic widespread pain and so-called fibromyalgia syndrome in children and adolescents. Systematic literature review and guideline]. / Definition, Diagnostik und Therapie von chronischen Schmerzen in mehreren Körperregionen und des sogenannten Fibromyalgiesyndroms bei Kindern und Jugendlichen. Systematische Literaturübersicht und Leitlinie.

BACKGROUND: The scheduled update to the German S3 guidelines on fibromyalgia syndrome (FMS) by the Association of the Scientific Medical Societies ("Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften", AWMF; registration number 041/004) was planned starting in March 2011. MATERIALS AND METHODS: The development of the guidelines was coordinated by the German Interdisciplinary Association for Pain Therapy ("Deutsche Interdisziplinären Vereinigung für Schmerztherapie", DIVS), 9 scientific medical societies and 2 patient self-help organizations. Eight working groups with a total of 50 members were evenly balanced in terms of gender, medical field, potential conflicts of interest and hierarchical position in the medical and scientific fields. Literature searches were performed using the Medline, PsycInfo, Scopus and Cochrane Library databases (until December 2010). The grading of the strength of the evidence followed the scheme of the Oxford Centre for Evidence-Based Medicine. The formulation and grading of recommendations was accomplished using a multi-step, formal consensus process. The guidelines were reviewed by the boards of the participating scientific medical societies. RESULTS AND CONCLUSION: The diagnosis FMS in children and adolescents is not established. In so-called juvenile FMS (JFMS) multidimensional diagnostics with validated measures should be performed. Multimodal therapy is warranted. In the case of severe pain-related disability, therapy should be primarily performed on an inpatient basis. The English full-text version of this article is available at SpringerLink (under "Supplemental").

Body size of twins compared with siblings and the general population: from birth to late adolescence.

OBJECTIVES: We examined whether and when differences in body size disappear over time and whether twins attain normal final height and body mass index (BMI). STUDY DESIGN: Height, weight, and BMI data of twins at ages 1, 4, and 18 years were compared with data from their nontwin siblings. Second, twin and sibling data were compared with population standards. In addition to height, weight, and BMI, data on body proportions at age 18 years were analyzed. RESULTS: At the age of 18 years, twins were as tall as their siblings but were significantly leaner. Compared with children from the general population, adolescent twins attained the same height and BMI. Birth weight was shown to have a considerable effect on height in adolescent twins. CONCLUSIONS: Twins attained normal final height compared with siblings and children from the general population. No differences in BMI were shown between 18-year-old twins and children from the general population, whereas the siblings of twins had increased BMI values compared with the general population.

Heritability of head size in Dutch and Australian twin families at ages 0-50 years.

We assessed the heritability of head circumference, an approximation of brain size, in twin-sib families of different ages. Data from the youngest participants were collected a few weeks after birth and from the oldest participants around age 50 years. In nearly all age groups the largest part of the variation in head circumference was explained by genetic differences. Heritability estimates were 90% in young infants (4 to 5 months), 85-88% in early childhood, 83-87% in adolescence, 75% in young and mid adulthood. In infants younger than 3 months, heritability was very low or absent. Quantitative sex differences in heritability were observed in 15- and 18-year-olds, but there was no evidence for qualitative sex differences, that is, the same genes were expressed in both males and females. Longitudinal analysis of the data between 5, 7, and 18 years of age showed high genetic stability (.78 > R(G) > .98). These results indicate that head circumference is a highly heritable biometric trait and a valid target for future GWA studies.

The Netherlands Twin Register biobank: a resource for genetic epidemiological studies.

In 2004 the Netherlands Twin Register (NTR) started a large scale biological sample collection in twin families to create a resource for genetic studies on health, lifestyle and personality. Between January 2004 and July 2008, adult participants from NTR research projects were invited into the study. During a home visit between 7:00 and 10:00 am, fasting blood and morning urine samples were collected. Fertile women were bled on day 2-4 of the menstrual cycle, or in their pill-free week. Biological samples were collected for DNA isolation, gene expression studies, creation of cell lines and for biomarker assessment. At the time of blood sampling, additional phenotypic information concerning health, medication use, body composition and smoking was collected. Of the participants contacted, 69% participated. Blood and urine samples were collected in 9,530 participants (63% female, average age 44.4 (SD 15.5) years) from 3,477 families. Lipid profile, glucose, insulin, HbA1c, haematology, CRP, fibrinogen, liver enzymes and creatinine have been assessed. Longitudinal survey data on health, personality and lifestyle are currently available for 90% of all participants. Genome-wide SNP data are available for 3,524 participants, with additional genotyping ongoing. The NTR biobank, combined with the extensive phenotypic information available within the NTR, provides a valuable resource for the study of genetic determinants of individual differences in mental and physical health. It offers opportunities for DNA-based and gene expression studies as well as for future metabolomic and proteomic projects.

A twin study of cognitive costs of low birth weight and catch-up growth.

OBJECTIVE: To investigate whether there is an association between catch-up growth and cognitive performance in humans. STUDY DESIGN: Catch-up growth was defined as the change in weight standard deviation scores during the first 2 years of life. Cognitive performance was assessed with psychometric IQ tests, administered at ages 12 and 18 years. Data were collected in twin pairs, and analyses were carried out within pairs. RESULTS: There was a significant negative association between catch-up growth and IQ at both ages 12 and 18 years. CONCLUSIONS: A larger gain in weight during the first 2 years of life is associated with a lower IQ. However, catch-up growth is correlated with birth weight and this correlation may explain part of the association.

Heritability of testis size.

Testis size is an important feature of male pubertal development. The genetic and environmental contributions to variation in human testis size have hardly been studied. We estimated the heritability of human testicular size in a group of mono- and dizygotic twins and their non-twin brothers (145 twins and 20 brothers from 95 families). Participants were 18 years old on average and all had reached Tanner development stage 4 or higher. Dizygotic twins and their siblings had a larger mean testis volume than monozygotic twins and their siblings. There was significant familial resemblance, with higher correlations in monozygotic twin pairs (0.59) than in dizygotic twin and sibling pairs (0.34). Heritability was estimated at 59% (95% CI = 37-75%), but a model that excluded genetic influences and attributed all familial resemblance to shared environment, fitted the data only marginally worse. The finding of larger mean testis volume in dizygotic twins may be of interest for future research into the mechanisms underlying dizygotic twinning.

Similarities and differences in lipidomics profiles among healthy monozygotic twin pairs.

Differences in genetic background and/or environmental exposure among individuals are expected to give rise to differences in measurable characteristics, or phenotypes. Consequently, genetic resemblance and similarities in environment should manifest as similarities in phenotypes. The metabolome reflects many of the system properties, and is therefore an important part of the phenotype. Nevertheless, it has not yet been examined to what extent individuals sharing part of their genome and/or environment indeed have similar metabolomes. Here we present the results of hierarchical clustering of blood plasma lipid profile data obtained by liquid chromatography-mass spectrometry from 23 healthy, 18-year-old twin pairs, of which 21 pairs were monozygotic, and 8 of their siblings. For 13 monozygotic twin pairs, within-pair similarities in relative concentrations of the detected lipids were indeed larger than the similarities with any other study participant. We demonstrate such high coclustering to be unexpected on basis of chance. The similarities between dizygotic twins and between nontwin siblings, as well as between nonfamilial participants, were less pronounced. In a number of twin pairs, within-pair dissimilarity of lipid profiles positively correlated with increased blood plasma concentrations of C-reactive protein in one twin. In conclusion, this study demonstrates that in healthy individuals, the individual genetic background contributes to the blood plasma lipid profile. Furthermore, lipid profiling may prove useful in monitoring health status, for example, in the context of personalized medicine.

Genetic regulation of growth in height and weight from 3 to 12 years of age: a longitudinal study of Dutch twin children.

Human growth is a complex and poorly understood process. We studied the effect of genetic and environmental factors on height and body mass index (BMI, kg/m(2)) based on maternal reports at 3, 4, 5, 7, 10 and 12 years of age in a large longitudinal cohort of Dutch twins (7755 complete twin pairs at age 3). Several multivariate variance component models for twins were fitted to the data using the Mx statistical package. The first-born twin was taller until age 10 and heavier until age 12 than the second-born co-twin. Heritability estimates were high for height (a(2) = .58-.91) and BMI (a(2) = .31-.82), but common and unshared environmental factors were also important. The phenotypic correlations across the ages for height and BMI were mainly explained by correlated additive genetic factors (r(a) = .77-.96 for height and .43-.92 for BMI), but common (r(c) = .40-.84 and .09-.78, respectively) and specific environmental correlations (r(e) = .50-.81 and .42-.80, respectively) were also significant. Additive genetic factors decreased with increasing age difference for both height and BMI. However, the full Cholesky model, which does not make any assumptions regarding the underlying genetic structure, had the best fit. High genetic correlations across the ages, especially for height, may help further molecular genetic studies of human growth. Environmental factors affecting height and BMI during growth period are also important, and further studies are needed to identify these factors and test whether they interact with genetic factors.

Body size in five-year-old twins: heritability and comparison to singleton standards.

The aim of this study is to examine causes of individual differences in height, weight and body mass index (BMI) in 5-year-old children registered with the Netherlands Twin Register. In addition, we examine whether the results of twin studies can be expanded to the singleton population by comparing the data from twins to Dutch reference growth data and by looking at the twins' target height, which was derived from parental height. For 2996 5-year-old twin pairs, information on height and weight and on parental height was available. Univariate and bivariate genetic analyses of height and weight and univariate analyses of BMI were conducted. In order to compare the twins to the singleton population, standard deviation scores (SDS) for height, BMI and target height were calculated based on Dutch reference growth charts for the general population from 1997. Genetic influences were an important source of variation in height, weight and BMI and the main source of covariation between height and weight. Additive genetic factors accounted for 69% and 66% of the individual differences in height in boys and girls, respectively. For weight, heritability estimates were 59% in boys and 78% in girls and for BMI 34% and 74%. The influence of common environment on height was 25% and 27%, on weight 24% and 10% and on BMI 44% and 12% in boys and girls. The bivariate model showed a large overlap between the genes influencing height and weight. Genes explain 78% (in boys) and 76% (in girls) of the covariance between weight and height. At the age of 5 years, female twins were as tall as singleton children, while male twins were shorter than singletons. For both boys and girls, however, mean height SDS was 0.6 standard deviation scores below the mean target height. All twins had lower BMI than singletons. Twins grow fairly well compared to singletons, but they grow below their target height. This may be due to the above average height of twin parents.

A young child who witnessed her mother's murder: therapeutic and legal considerations.

For the clinician treating children who have witnessed parent-parent homicide, complex and conflicting therapeutic and case management issues must be confronted. The goals of treatment of these children include relief of suffering and resolution of symptoms, clarification of cognitive or emotional distortions about the traumatic experience, provision of a supportive posttraumatic environment in which the child may continue to work through the experience as needed in the future, and minimization of future problems as a result of the trauma. When these goals have been substantially achieved, the child should be able to resume age appropriate developmental tasks. The clinician must also advocate for the child in the legal process despite not having a clearly defined role in the criminal justice system. The goal of involvement as consultant to the legal system is to minimize further psychological trauma to the child who is at risk for reexperiencing trauma for nontherapeutic purposes, creation of intense loyalty conflict, confrontation with the accused parent, intimidating cross-examination, and responsibility for deciding the fate of one's parent. The paucity of previous reports on this topic suggests that such children are infrequently referred for psychiatric treatment despite data indicating these cases are tragically not uncommon. It seems incumbent upon mental health professionals to increase awareness in the community in general and in the criminal justice system in particular about the need for psychiatric treatment of these children at risk.

[Acrodermatitis enteropathica (AE) is caused by mutations in the zinc transporter gene SLC39A4]. / Acrodermatitis enteropathica (AE) wird durch Mutationen im Zink-Transportergen SLC39A4 verursacht.

BACKGROUND: Acrodermatitis enteropathica (AE) is an autosomal recessively inherited disease caused by a decreased intestinal zinc resorption and characterized by severe dermatitis (preferably hands, feet, mouth, genital region), chronic diarrhoea, retardation of growth and development, alopecia and increased proneness to infections. In 2002 it was shown that mutations in the zinc transporter gene SLC39A4 is the cause of AE. CASE REPORT: Here we report 4 patients with typical clinical signs since early childhood. Under regular substitution with zinc all patients are more or less free of symptoms. The first patient revealed compound-heterozygous missense/nonsense mutations (P200L/ W401X), the three other patients were homozygous for a mutation in intron 1 (c.192 + 19G > A) of the SLC39A4 gene. CONCLUSION: The diagnosis of hereditary acrodermatitis enteropathica can now easily be confirmed by mutation analysis of the SLC39A4 gene.

[Pain therapy in acute pediatric diseases and vaccination]. / Schmerztherapie bei akuten pädiatrischen Erkrankungen und Impfungen.

PHENOMENON PAIN: While pain is one of the main reasons for an unscheduled visit to the paediatrician, pain due to painful procedures is of major importance in scheduled visits. Actual pain therapy is illustrated in the treatment of burns. Incomplete analgesia may have an unfavourable impact on morbidity and mortality. The pain score does not correlate with the extent of the burned area, and is regularly underestimated. General anaesthesia or analgo-sedation are warranted during the care of the burned patient. INSUFFICIENT ANALGESIA: Consequence of insufficient analgesia during primary care is an increased need of analgesics, and an increased pain treatment failure rate during subsequent procedures. Pain is interfering with anxiety, sleep disturbances and post-traumatic psychologic alterations. All those symptoms must be treated adequately. ACUTE ILLNESS AND INJECTIONS: This article covers pain from otitis media, pharyngitis, Guillain-Barré syndrome, purpura fulminans, Toxic Epidermal Nekrolysis, as well as the usage of local anaesthesia during injections, not to forget the application of non-pharmacologic methods for pain therapy and prophylaxis.

[Musculoskeletal pain]. / Muskuloskelettale Schmerzen.

BACKGROUND: In paediatrics, numerous diseases present with the leading symptom of muscular, articular, or bone-related pain. The pain as such is seldom diagnostic with regard to pain etiology. Regularly, the significance of inflammatory as well as non-inflammatory pain is underestimated. CLASSIFICATION OF MUSCULOSKELETAL DISEASES: We present 4 case reports, illustrating the classification of musculoskeletal diseases into 4 main groups, being the basis for the modelling of disease, and pain treatment. THERAPY: Pain therapy is either symptomatic or based on specific pathophysiology. Pain therapy consists of the moduls analgesics, antiphlogistics, physiotherapy, psychosocial support, and complementary therapies. We give advice on differential therapy. A transparent team-oriented concept comprising physicians, physiotherapists, ergotherapists, psychologists, and social workers is the basis for any successful long-term therapy. Regular outpatient visits in consent with the family doctor are mandatory as are education and treatment periods on ward. We encourage our patients to join formal self-supportive patient groups.

[Spondylodiscitis in childhood]. / Die Spondylodiszitis im Kindesalter.

Spondylodiscitis is a frequently unrecognized disease in childhood because of unspecific symptoms and late arising or radiological signs. The heterogeneous symptoms, the value of diagnostic procedures and the outcome of 8 patients suffering from spondylodiscitis in the time period of 1989 to 1995 are demonstrated. Guiding symptoms were back pain and refusal to walk or sit. Furthermore, abdominal pain and psoas abscess were the only symptoms in two cases. The pathogenomonical narrowing of the disc space arose in X-ray films earliest 3 weeks after onset of symptoms. The MRI was the best method for early diagnosis and detection of complications. In contrast to persistent radiological changes the clinical outcome was good in most of the patients.

Chronic osteomyelitis in childhood: is surgery always indicated?

BACKGROUND: Presently, most children with chronic osteomyelitis undergo surgery with the inherent risk of damage to their growth plate. We demonstrate a treatment regimen based on imaging procedures focussing on antibiotics in order to reduce the rate of surgical interventions. PATIENTS AND METHODS: We retrospectively evaluated all 11 patients with clinically suspected chronic osteomyelitis who were treated at our institution from 1989 to 1995. Patients underwent open biopsy and surgical treatment only if imaging procedures showed signs indistinguishable from malignancy, or if they were highly suggestive for the presence of pus, joint infection or osteonecrosis. The patients were followed up for a minimum of 3 years. RESULTS: All five patients treated solely with antibiotics recovered completely. Three patients were subjected to open biopsy and surgical treatment since they showed radiological signs indistinguishable from malignancy, and two patients due to pus or osteonecrosis. In follow-up, there was one relapse of chronic osteomyelitis 11 months after the first treatment course with surgery and antibiotics. One patient suffering from Ewing's sarcoma as detected by open biopsy was excluded. CONCLUSION: Our diagnostic procedure was useful to reduce the rate of surgery. Surgical treatment of chronic osteomyelitis is not always neccessary especially in cases of missing necrosis, joint infection and abscess as demonstrated by the complete recovery of our patients treated solely with antibiotics.

[Vomiting as main symptom: unusual presentation of a hyperthyroidism in a 12-year-old boy]. / Erbrechen als Leitsymptom: Ungewöhnliche Präsentation einer Hyperthyreose bei einem zwölfjährigen Jungen.

A twelve year old boy presented with a sudden onset of recurrent nausea and vomiting. During the past six weeks he had a weight loss of 13 kg. While he was in the hospital, persistent tachycardia and a slightly elevated blood pressure were noted. The gastroenterologic, cardiologic and neuropediatric examinations were normal. To exclude the differential diagnosis of hyperthyroidism, thyroid hormones were checked. They showed clearly elevated levels of tri-iodothyronine and thyroxine, while thyrotropin was suppressed. The boy did not have a goiter. Under thyrostatic therapy his clinical condition improved quickly. Among our 20 patients with hyperthyroidism he was the only one whose main symptom was severe vomiting.