Compliance with recommended immunizations in adolescents

Introduction: Little is known about the completeness and timely administration of recommended standard immunizations in Germany. The goal of this study was to determine compliance with official standard immunization recommendations in adolescents attending secondary schools in the city of Erlangen, Germany. Methods: Adolescents who were attending 5th grade (at approximately 11years of age), 8th grade (14years), or 10th and 11th grade (16-17years) classes at any of the 13 of 14 schools that had agreed to participate were eligible to be enrolled. Results: While coverage for the primary series of diphtheria, tetanus and poliomyelitis immunizations was satisfactory (98%), coverage for measles-mumps-rubella immunizations (dose 1: 89-96%; dose 2: 60-76%) and hepatitis B (doses 1-3: 61%) was suboptimal. Of note, 39% of students had not received any immunization against pertussis. Completion of immunization series generally was significantly delayed. Furthermore, rates for recommended booster doses in adolescence were disappointingly low with 21% for tetanus component vaccines and <10% for the fifth dose of pertussis. Conclusions: Significant immunization gaps for all recommended standard immunizations in adolescents were detected. This puts individuals at risk for serious vaccine-preventable diseases, contributes to suboptimal herd immunity in the population under study leaving the potential for future epidemics, and impedes national and international targets of disease reduction or eliminatio

Hydrochlorothiazide in CLDN16 mutation

Background. Hydrochlorothiazide (HCT) is applied in the therapy of familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC) caused by claudin-16 (CLDN16) mutation. However, the short-term efficacy of HCT to reduce hypercalciuria in FHHNC has not yet been demonstrated in a clinical trial. Methods. Four male and four female patients with FHHNC and CLDN16 mutation, under long-standing HCT therapy (0.4-1.2 mg/kg, median 0.9 mg/kg, dose according to calciuria), aged 0.7-22.4 years, were included in a clinical study to investigate the effect of HCT on calciuria. The study design consisted of three periods: continued therapy for 4 weeks, HCT withdrawal for 6 weeks and restart of therapy at the same dose for 4 weeks. Calciuria and magnesiuria were assessed weekly as Ca/creat and Mg/creat ratio, every 2 weeks in 24 h urine, and serum Mg, K and kaliuria (s-Mg, s-K and K/creat) at weeks 0, 6, 10 and 14. The data of each study period were averaged and analysed by Friedman and Wilcoxon test. Results. Ca/creat was significantly reduced by HCT (median before/at/after withdrawal 0.76/1.24/0.77 mol/mol creat; n = 8, P<0.05). The reduction of Ca/24 h by HCT was not statistically significant (0.13/0.19/0.13 mmol/kg × 24 h; n = 5). Serum Mg (0.51/0.64/0.56 mmol/l; n = 8, P<0.05) and Serum K (3.65/4.35/3.65 mmol/l; n = 8, P<0.05) were significantly higher during withdrawal. However, Mg/creat (0.98/0.90/0.90 mol/mol creat; n = 8), Mg/24 h (0.14/0.12/0.18 mmol/kg × 24h; n = 5) and K/creat (6.3/8.4/6.2 mol/mol creat; n = 8) remained statistically unchanged during withdrawal. Conclusions. We demonstrated that HCT is effective in reducing hypercalciuria due to CLDN16 mutation on a short-term basis. However, the efficacy of HCT to attenuate disease progression remains to be elucidate

An exceptional Albanian family with seven children presenting with dysmorphic features and mental retardation: maternal phenylketonuria

BACKGROUND: Phenylketonuria is an inborn error of amino acid metabolism which can cause severe damage to the patient or, in the case of maternal phenylketonuria, to the foetus. The maternal phenylketonuria syndrome is caused by high blood phenylalanine concentrations during pregnancy and presents with serious foetal anomalies, especially congenital heart disease, microcephaly and mental retardation. CASE PRESENTATION: We report on an affected Albanian woman and her seven children. The mother is affected by phenylketonuria and is a compound heterozygote for two pathogenetic mutations, L48S and P281L. The diagnosis was only made in the context of her children, all of whom have at least one severe organic malformation. The first child, 17 years old, has a double-chambered right ventricle, vertebral malformations and epilepsy. She is also mentally retarded, microcephalic, exhibits facial dysmorphies and small stature. The second child, a girl 15 years of age, has severe mental retardation with microcephaly, small stature and various dysmorphic features. The next sibling, a boy, died of tetralogy of Fallot at the age of three months. He also had multiple vertebral and rib malformations. The subsequent girl, now eleven years old, has mental retardation, microcephaly and epilepsy along with facial dysmorphy, partial deafness and short stature. The eight-year-old child is slightly mentally retarded and microcephalic. A five-year-old boy was a premature, dystrophic baby and exhibits mental retardation, dysmorphic facial features, brachydactyly and clinodactyly of the fifth finger on both hands. Following a miscarriage, our index case, the youngest child at two years of age, is microcephalic and mentally retarded and shows minor facial anomalies. All children exhibit features of phenylalanine embryopathy caused by maternal phenylketonuria because the mother had not been diagnosed earlier and, therefore, never received any diet. CONCLUSION: This is the largest family suffering from maternal phenylketonuria reported in the literature. Maternal phenylketonuria remains a challenge, especially in woman from countries without a neonatal screening program. Therefore, it is mandatory to be alert for the possibility of maternal phenylketonuria syndrome in case of a child with the clinical features described here to prevent foetal damage in subsequent siblings

2016 European Society of Hypertension guidelines for the management of high blood pressure in children and adolescents

Increasing prevalence of hypertension (HTN) in children and adolescents has become a significant public health issue driving a considerable amount of research. Aspects discussed in this document include advances in the definition of HTN in 16 year or older, clinical significance of isolated systolic HTN in youth, the importance of out of office and central blood pressure measurement, new risk factors for HTN, methods to assess vascular phenotypes, clustering of cardiovascular risk factors and treatment strategies among others. The recommendations of the present document synthesize a considerable amount of scientific data and clinical experience and represent the best clinical wisdom upon which physicians, nurses and families should base their decisions. In addition, as they call attention to the burden of HTN in children and adolescents, and its contribution to the current epidemic of cardiovascular disease, these guidelines should encourage public policy makers to develop a global effort to improve identification and treatment of high blood pressure among children and adolescents

Lack of α8 integrin leads to morphological changes in renal mesangial cells, but not in vascular smooth muscle cells

<p>Abstract</p> <p>Background</p> <p>Extracellular matrix receptors of the integrin family are known to regulate cell adhesion, shape and functions. The α8 integrin chain is expressed in glomerular mesangial cells and in vascular smooth muscle cells. Mice deficient for α8 integrin have structural alterations in glomeruli but not in renal arteries. For this reason we hypothesized that mesangial cells and vascular smooth muscle cells differ in their respective capacity to compensate for the lack of α8 integrin.</p> <p>Results</p> <p>Wild type and α8 integrin-deficient mesangial cells varied markedly in cell morphology and expression or localization of cytoskeletal molecules. In α8 integrin-deficient mesangial cells α-smooth muscle actin and CTGF were downregulated. In contrast, there were no comparable differences between α8 integrin-deficient and wild type vascular smooth muscle cells. Expression patterns of integrins were altered in α8 integrin-deficient mesangial cells compared to wild type mesangial cells, displaying a prominent overexpression of α2 and α6 integrins, while expression patterns of the these integrins were not different between wild type and α8 integrin-deficient vascular smooth muscle cells, respectively. Cell proliferation was augmented in α8 integrin-deficient mesangial cells, but not in vascular smooth muscle cells, compared to wild type cells.</p> <p>Conclusions</p> <p>Our findings suggest that α8 integrin deficiency has differential effects in mesangial cells and vascular smooth muscle cells. While the phenotype of vascular smooth muscle cells lacking α8 integrin is not altered, mesangial cells lacking α8 integrin differ considerably from wild type mesangial cells which might be a consequence of compensatory changes in the expression patterns of other integrins. This could result in glomerular changes in α8 integrin-deficient mice, while the vasculature is not affected in these mice.</p

Intrauterine growth restriction promotes vascular remodelling following carotid artery ligation in rats

A B S T R A C T Epidemiological studies revealed an association between IUGR (intrauterine growth restriction) and an increased risk of developing CVDs (cardiovascular diseases), such as atherosclerosis or hypertension, in later life. Whether or not IUGR contributes to the development of atherosclerotic lesions, however, is unclear. We tested the hypothesis that IUGR aggravates experimentally induced vascular remodelling. IUGR was induced in rats by maternal protein restriction during pregnancy (8 % protein diet). To detect possible differences in the development of vascular injury, a model of carotid artery ligation to induce vascular remodelling was applied in 8-week-old intrauterinegrowth-restricted and control rat offspring. Histological and immunohistochemical analyses were performed in the ligated and non-ligated carotid arteries 8 weeks after ligation. IUGR alone neither caused overt histological changes nor significant dedifferentiation of VSMCs (vascular smooth muscle cells). After carotid artery ligation, however, neointima formation, media thickness and media/lumen ratio were significantly increased in rats after IUGR compared with controls. Moreover, dedifferentiation of VSMCs and collagen deposition in the media were more prominent in ligated carotids from rats after IUGR compared with ligated carotids from control rats. We conclude that IUGR aggravates atherosclerotic vascular remodelling induced by a second injury later in life

Influence of Low Protein Diet-Induced Fetal Growth Restriction on the Neuroplacental Corticosterone Axis in the Rat

Objectives: Placental steroid metabolism is linked to the fetal hypothalamus-pituitary-adrenal axis. Intrauterine growth restriction (IUGR) might alter this cross-talk and lead to maternal stress, in turn contributing to the pathogenesis of anxiety-related disorders of the offspring, which might be mediated by fetal overexposure to, or a reduced local enzymatic protection against maternal glucocorticoids. So far, direct evidence of altered levels of circulating/local glucocorticoids is scarce. Liquid chromatography tandem-mass spectrometry (LC-MS/MS) allows quantitative endocrine assessment of blood and tissue. Using a rat model of maternal protein restriction (low protein [LP] vs. normal protein [NP]) to induce IUGR, we analyzed fetal and maternal steroid levels via LC-MS/MS along with the local expression of 11beta-hydroxysteroid-dehydrogenase (Hsd11b).Methods: Pregnant Wistar dams were fed a low protein (8%, LP; IUGR) or an isocaloric normal protein diet (17%, NP; controls). At E18.5, the expression of Hsd11b1 and 2 was determined by RT-PCR in fetal placenta and brain. Steroid profiling of maternal and fetal whole blood, fetal brain, and placenta was performed via LC-MS/MS.Results: In animals with LP-induced reduced body (p &lt; 0.001) and placental weights (p &lt; 0.05) we did not observe any difference in the expressional Hsd11b1/2-ratio in brain or placenta. Moreover, LP diet did not alter corticosterone (Cort) or 11-dehydrocorticosterone (DH-Cort) levels in dams, while fetal whole blood levels of Cort were significantly lower in the LP group (p &lt; 0.001) and concomitantly in LP brain (p = 0.003) and LP placenta (p = 0.002). Maternal and fetal progesterone levels (whole blood and tissue) were not influenced by LP diet.Conclusion: Various rat models of intrauterine stress show profound alterations in placental Hsd11b2 gatekeeper function and fetal overexposure to corticosterone. In contrast, LP diet in our model induced IUGR without altering maternal steroid levels or placental enzymatic glucocorticoid barrier function. In fact, IUGR offspring showed significantly reduced levels of circulating and local corticosterone. Thus, our LP model might not represent a genuine model of intrauterine stress. Hypothetically, the observed changes might reflect a fetal attempt to maintain anabolic conditions in the light of protein restriction to sustain regular brain development. This may contribute to fetal origins of later neurodevelopmental sequelae

Early and Late Postnatal Myocardial and Vascular Changes in a Protein Restriction Rat Model of Intrauterine Growth Restriction

Intrauterine growth restriction (IUGR) is a risk factor for cardiovascular disease in later life. Early structural and functional changes in the cardiovascular system after IUGR may contribute to its pathogenesis. We tested the hypothesis that IUGR leads to primary myocardial and vascular alterations before the onset of hypertension. A rat IUGR model of maternal protein restriction during gestation was used. Dams were fed low protein (LP; casein 8.4%) or isocaloric normal protein diet (NP; casein 17.2%). The offspring was reduced to six males per litter. Immunohistochemical and real-time PCR analyses were performed in myocardial and vascular tissue of neonates and animals at day 70 of life. In the aortas of newborn IUGR rats expression of connective tissue growth factor (CTGF) was induced 3.2-fold. At day 70 of life, the expression of collagen I was increased 5.6-fold in aortas of IUGR rats. In the hearts of neonate IUGR rats, cell proliferation was more prominent compared to controls. At day 70 the expression of osteopontin was induced 7.2-fold. A 3- to 7-fold increase in the expression of the profibrotic cytokines TGF-β and CTGF as well as of microfibrillar matrix molecules was observed. The myocardial expression and deposition of collagens was more prominent in IUGR animals compared to controls at day 70. In the low-protein diet model, IUGR leads to changes in the expression patterns of profibrotic genes and discrete structural abnormalities of vessels and hearts in adolescence, but, with the exception of CTGF, not as early as at the time of birth. Invasive and non-invasive blood pressure measurements confirmed that IUGR rats were normotensive at the time point investigated and that the changes observed occurred independently of an increased blood pressure. Hence, altered matrix composition of the vascular wall and the myocardium may predispose IUGR animals to cardiovascular disease later in life