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Sample records for early onset preeclampsia

  1. Associations of personal and family preeclampsia history with the risk of early-, intermediate- and late-onset preeclampsia.

    Science.gov (United States)

    Boyd, Heather A; Tahir, Hassaan; Wohlfahrt, Jan; Melbye, Mads

    2013-12-01

    Preeclampsia encompasses multiple conditions of varying severity. We examined the recurrence and familial aggregation of preeclampsia by timing of onset, which is a marker for severity. We ascertained personal and family histories of preeclampsia for women who delivered live singletons in Denmark in 1978-2008 (almost 1.4 million pregnancies). Using log-linear binomial regression, we estimated risk ratios for the associations between personal and family histories of preeclampsia and the risk of early-onset (before 34 weeks of gestation, which is typically the most severe), intermediate-onset (at 34-36 weeks of gestation), and late-onset (after 36 weeks of gestation) preeclampsia. Previous early-, intermediate-, or late-onset preeclampsia increased the risk of recurrent preeclampsia with the same timing of onset 25.2 times (95% confidence interval (CI): 21.8, 29.1), 19.7 times (95% CI: 17.0, 22.8), and 10.3 times (95% CI: 9.85, 10.9), respectively, compared with having no such history. Preeclampsia in a woman's family was associated with a 24%-163% increase in preeclampsia risk, with the strongest associations for early- and intermediate-onset preeclampsia in female relatives. Preeclampsia in the man's family did not affect a woman's risk of early-onset preeclampsia and was only weakly associated with her risks of intermediate- and late-onset preeclampsia. Early-onset preeclampsia appears to have the largest genetic component, whereas environmental factors likely contribute most to late-onset preeclampsia. The role of paternal genes in the etiology of preeclampsia appears to be limited.

  2. Maternal serum copeptin concentrations in early- and late-onset pre-eclampsia

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    Abdullah Tuten

    2015-08-01

    Conclusion: Our results suggest that copeptin levels might be useful in the evaluation of the severity of pre-eclampsia. However, copeptin might be involved in early- rather than late-onset pre-eclampsia.

  3. Intrauterine growth restriction and placental gene expression in severe preeclampsia, comparing early-onset and late-onset forms.

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    Nevalainen, Jaana; Skarp, Sini; Savolainen, Eeva-Riitta; Ryynänen, Markku; Järvenpää, Jouko

    2017-10-26

    To evaluate placental gene expression in severe early- or late-onset preeclampsia with intrauterine growth restriction compared to controls. Chorionic villus sampling was conducted after cesarean section from the placentas of five women with early- or late-onset severe preeclampsia and five controls for each preeclampsia group. Microarray analysis was performed to identify gene expression differences between the groups. Pathway analysis showed over-representation of gene ontology (GO) biological process terms related to inflammatory and immune response pathways, platelet development, vascular development, female pregnancy and reproduction in early-onset preeclampsia. Pathways related to immunity, complement and coagulation cascade were overrepresented in the hypergeometric test for the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Ten genes (ABI3BP, C7, HLA-G, IL2RB, KRBOX1, LRRC15, METTL7B, MPP5, RFLNB and SLC20A) had a ≥±1 fold expression difference in severe early-onset preeclampsia group compared to early controls. There were 362 genes that had a ≥±1 fold expression difference in severe early-onset preeclampsia group compared to late-onset preeclampsia group including ABI3BP, C7, HLA-G and IL2RB. There are significant differences in placental gene expression between severe early- and late-onset preeclampsia when both are associated with intrauterine growth restriction. ABI3BP, C7, HLA-G and IL2RB might contribute to the development of early form of severe preeclampsia.

  4. Different Profile of Serum Leptin between Early Onset and Late Onset Preeclampsia

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    Saeedeh Salimi

    2014-01-01

    Full Text Available Aim. This study was designed to clarify the role of leptin and adiponectin in preeclampsia (PE pathogenesis and different subtypes of preeclampsia. Method. This case control study was performed in 45 PE patients and 45 healthy controls matched for age, BMI, and ethnicity. Serum leptin and adiponectin levels were determined by enzyme linked immunosorbent assay (ELISA. Results. Maternal serum leptin and adiponectin were significantly higher in PE women than controls. Serum leptin was elevated in early onset preeclampsia (EOPE and late onset preeclampsia (LOPE compared to controls. Among PE patients, serum leptin was higher in EOPE than LOPE women. However, serum adiponectin was not different between EOPE and LOPE women. The serum leptin was significantly higher in severe PE than mild PE. The serum adiponectin was significantly elevated in severe PE compared to controls. Significant positive correlation was observed between leptin and adiponectin and also between leptin and BMI in controls. Moreover significant positive correlation was observed between adiponectin and BMI in PE patients and controls. Conclusion. The present study showed that serum leptin level may play a significant role as a biomarker to differentiate early and late onset PE and also its relation to BMI and severity of disease.

  5. Circulatory nucleosome levels are significantly increased in early and late-onset preeclampsia.

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    Zhong, Xiao Yan; Gebhardt, Stefan; Hillermann, Renate; Tofa, Kashefa Carelse; Holzgreve, Wolfgang; Hahn, Sinuhe

    2005-08-01

    Elevations in circulatory DNA, as measured by real-time PCR, have been observed in pregnancies with manifest preeclampsia. Recent reports have indicated that circulatory nucleosome levels are elevated in the periphery of cancer patients. We have now examined whether circulatory nucleosome levels are similarly elevated in cases with preeclampsia. Maternal plasma samples were prepared from 17 cases with early onset preeclampsia (34 weeks gestation) with 10 matched normotensive controls. Levels of circulatory nucleosomes were quantified by commercial ELISA (enzyme-linked immunosorbant assay). The level of circulatory nucleosomes was significantly elevated in both study preeclampsia groups, compared to the matched normotensive control group (p = 0.000 and p = 0.001, respectively). Our data suggests that preeclampsia is associated with the elevated presence of circulatory nucleosomes, and that this phenomenon occurs in both early- and late-onset forms of the disorder. Copyright 2005 John Wiley & Sons, Ltd.

  6. Early-onset preeclampsia is associated with perinatal mortality and severe neonatal morbidity

    NARCIS (Netherlands)

    Esch, J.J.A. van; Heijst, A.F. van; Haan, A.F.J. de; Heijden, O.W.H. van der

    2017-01-01

    OBJECTIVE: To evaluate neonatal outcomes of pregnancies complicated by early-onset preeclampsia (PE) and compare these outcomes to those of gestational age matched neonates born to mothers whose pregnancy was not complicated by early-onset PE. METHODS: We analyzed the outcome in 97 neonates born to

  7. ASSESSMENT OF OXIDATIVE STRESS IN EARLY AND LATE ONSET PRE-ECLAMPSIA AMONG GHANAIAN WOMEN.

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    Tetteh, P W; Adu-Bonsaffoh, K; Antwi-Boasiako, C; Antwi, D A; Gyan, B; Obed, S A

    2015-01-01

    Pre-eclampsia is a multisystem pregnancy-related disorder with multiple theories regarding its aetiology resulting in lack of reliable screening tests and well-established measures for primary prevention. However, oxidative stress is increasingly being implicated in the pathogenesi of pre-eclampsia although conflicting findings have been reported. To determine and compare the levels of oxidative stress in early and late onset pre-eclampsia by measuring urinary excretion of isoprostane and total antioxidant power (TAP) in a cohort of pre-eclamptic women at Korle Bu Teaching Hospital. This was a cross-sectional study conducted at Korle-Bu Teaching Hospital, Accra, Ghana involving pre-eclamptic women between the ages 18 and 45 years who gave written informed consent. Urinary isoprostane levels were determined using an enzyme-linked immunosorbent assay (ELISA) kit whereas the Total Anti-oxidant Power in urine samples was determined using Total Antioxidant Power Colorimetric Microplate Assay kit. The data obtained were analyzed using MEGASTAT statistical software package. We included 102 pre-eclamptic women comprising 68 (66.7%) and 34 (33.3%) with early-onset and late-onset pre-eclampsia respectively. There were no statistically significant differences between the mean maternal age, haematological indices, serum ALT, AST, ALT, albumin, urea, creatinine uric acid and total protein at the time of diagnosis. The mean gestational age at diagnosis of early and late onset pre-eclampsia were 31.65 ± 0.41 and 38.03 ± 0.21 respectively (p ˂ 0.001). Also, there were statistically significant differences between the diastolic blood pressure (BP), systolic BP and mean arterial pressure (MAP) at diagnosis of pre-eclampsia in the two categories. The mean urinary Isoprostane excretion was significantly higher in the early onset pre-eclamptic group (3.04 ± 0.34 ng/mg Cr) compared to that of the late onset pre-eclamptic group (2.36 ± 0.45 ng/mg Cr), (p=0.019). Urinary total

  8. The association of with severe early-onset pre-eclampsia

    African Journals Online (AJOL)

    however also found no differences in APA levels between patients with severe early-onset pre-eclampsia and controls."lO Further, Kilpatrick et a/.'°state that even Branch et a/. 6 found ACAs in only 16% of their patients. In the present study, both ACA and LAC levels were assayed, and all 4 patients had significantly raised ...

  9. First trimester screening for intra-uterine growth restriction and early-onset pre-eclampsia

    NARCIS (Netherlands)

    Vandenberghe, G.; Mensink, I.; Twisk, J. W. R.; Blankenstein, M. A.; Heijboer, A. C.; van Vugt, J. M. G.

    2011-01-01

    To assess first trimester placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A) as screening markers for early-onset pre-eclampsia (PE) and intra-uterine growth restriction (IUGR). PlGF concentration was retrospectively measured in first trimester serum specimens of 23

  10. First trimester screening for intra-uterine growth restriction and early-onset pre-eclampsia

    NARCIS (Netherlands)

    Vandenberghe, G.; Mensink, I.; Twisk, J.W.; Blankenstein, M.A.; Heijboer, A.C.; van Vugt, J.M.

    2011-01-01

    Objective: To assess first trimester placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A) as screening markers for early-onset pre-eclampsia (PE) and intra-uterine growth restriction (IUGR). Methods: PlGF concentration was retrospectively measured in first trimester

  11. Polycystic ovary syndrome and early-onset preeclampsia: reproductive manifestations of increased cardiovascular risk.

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    Veltman-Verhulst, Susanne M; van Rijn, Bas B; Westerveld, H Egbertine; Franx, Arie; Bruinse, Hein W; Fauser, Bart C J M; Goverde, Angelique J

    2010-01-01

    Primary prevention of cardiovascular disease (CVD) in women is a major healthcare issue. Detection of premenopausal women with increased risk of CVD could enhance prevention strategies and reduce first event-related morbidity and mortality. In this study, we argue that an unfavorable metabolic constitution in women may present itself early in life as a reproductive complication, such as polycystic ovary syndrome (PCOS) and preeclampsia. We evaluated the cardiovascular risk of women with a history of early-onset preeclampsia and women with PCOS and assessed their need for implementation of early risk factor-reduction strategies. We performed a standardized evaluation of 240 women with a history of early-onset preeclampsia and 456 women diagnosed with PCOS for established major CVD risk factors. Metabolic syndrome characteristics were analyzed per body mass index category. Mean age was 30.6 and 29.0 years for women with preeclampsia and PCOS, respectively. High percentages of metabolic syndrome were found in both groups (preeclampsia group, 14.6%; and PCOS group, 18.4%), with an incidence of greater than 50% in both groups of women if body mass index was greater than 30 kg/m. Overall, more than 90% of the women qualified for either lifestyle or medical intervention according to the American Heart Association guideline for CVD prevention in women. Women with PCOS and early-onset preeclampsia already show an unfavorable cardiovascular risk profile with high need for lifestyle or medical intervention at a young age. We therefore recommend an active role of the gynecologist in routine screening and follow-up of women with reproductive conditions linked to future cardiovascular risk.

  12. Vasoactive agents for the prediction of early- and late-onset preeclampsia in a high-risk cohort

    Science.gov (United States)

    2013-01-01

    Background To evaluate the soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and sFlt-1/PlGF ratio for the prediction of early- and late-onset preeclampsia in a high-risk cohort. Methods We studied serial serum samples collected prospectively at 12 + 0 - 14 + 0, 18 + 0 - 20 + 0, and 26 + 0 - 28 + 0 weeks + days of gestation in 6 women who developed early-onset preeclampsia (before 34 weeks of gestation) and in 21 women who developed late-onset preeclampsia (after 34 weeks of gestation) with automated ElecSys 2010 immunoanalyzer (Roche Diagnostics, Germany). Twenty-six high-risk women and 53 women without risk factors with normal pregnancies served as controls. Results Serum PlGF concentrations were lower at 18 + 0 to 20 + 0, and 26 + 0 to 28 + 0 weeks of gestation in women who developed early-onset preeclampsia compared to women who developed late-onset preeclampsia and to controls (p preeclampsia (AUC 100.0%, p = 0.0007, 95% CI 100–100). Amongst women with late-onset preeclampsia, those who developed severe form of the disease (N = 8) had significantly higher serum sFlt-1 concentrations at all three timepoints (p = 0.004, p = 0.006, and p = 0.003, respectively) compared to women with non-severe form (N = 13). Conclusions Low serum PlGF concentration predicts early-onset preeclampsia from the second trimester and elevated serum sFlt-1/PlGF ratio from 26 to 28 weeks of gestation. Elevated serum sFlt-1 concentration in the first trimester in women who later develop late-onset, severe preeclampsia may suggest different etiology compared to the late-onset non-severe form of the disease. PMID:23663420

  13. Fetal Microsatellite in the Heme Oxygenase 1 Promoter Is Associated With Severe and Early-Onset Preeclampsia.

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    Kaartokallio, Tea; Utge, Siddheshwar; Klemetti, Miira M; Paananen, Jussi; Pulkki, Kari; Romppanen, Jarkko; Tikkanen, Ilkka; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Kivinen, Katja; Pouta, Anneli; Lakkisto, Päivi; Laivuori, Hannele

    2018-01-01

    Preeclampsia is a vascular pregnancy disorder that often involves impaired placental development. HO-1 (heme oxygenase 1, encoded by HMOX1 ) is a stress response enzyme crucial for endothelial and placental function. Long version of the guanine-thymine (GT n ) microsatellite in the HMOX1 promoter decreases HO-1 expression, and the long maternal repeat is associated with late-onset preeclampsia. Our aim was to study whether the length of fetal repeat is associated with mother's preeclampsia, whether the length of fetal and maternal repeats affect HO-1 levels in placenta and maternal serum, and whether HO-1 levels are altered in preeclampsia. We genotyped the repeat in the cord blood of 609 preeclamptic and 745 nonpreeclamptic neonates. HO-1 levels were measured in 36 placental samples, and in the first (222 cases/243 controls) and third (176 cases/53 controls) pregnancy trimester serum samples using enzyme-linked immunosorbent assay. The long fetal GT n repeat was associated with preeclampsia and its severe and early-onset subtypes. Interaction analysis suggested the maternal and fetal effects to be independent. Placental or serum HO-1 levels were not altered in preeclamptics, possibly reflecting heterogeneity of preeclampsia. Carriers of the long fetal and maternal repeats had lower placental and serum HO-1 levels, respectively, providing functional evidence for the association. We conclude that the long fetal GT n repeat may increase mother's risk for especially severe and early-onset preeclampsia. The fetal and maternal risk alleles likely predispose to different disease subtypes. © 2017 American Heart Association, Inc.

  14. The definition of severe and early-onset preeclampsia. Statements from the International Society for the Study of Hypertension in Pregnancy (ISSHP).

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    Tranquilli, Andrea L; Brown, Mark A; Zeeman, Gerda G; Dekker, Gustaaf; Sibai, Baha M

    2013-01-01

    There is discrepancy in the literature on the definitions of severe and early-onset pre-eclampsia. We aimed to determine those definitions for clinical purposes and to introduce them in the classification of the hypertensive disorders of pregnancy for publication purposes. We circulated a questionnaire to the International Committee of the International Society for the Study of Hypertension in Pregnancy focusing on the thresholds for defining severe preeclampsia and the gestation at which to define early-onset preeclampsia, and on the definition and inclusion of the HELLP syndrome or other clinical features in severe preeclampsia. The questions were closed, but all answers had space for more open detailed comments. There was a general agreement to define preeclampsia as severe if blood pressure was >160mmHg systolic or 110mmHg diastolic. There was scarce agreement on the amount of proteinuria to define severity. The HELLP syndrome was considered a feature to include in the severe classification. Most investigators considered early-onset preeclampsia as that occurring before 34weeks. A definition of pre-eclampsia is paramount for driving good clinical practice. Classifications on the other hand are useful to enable international comparisons of clinical data and outcomes. We used the results of this survey to update our previous classification for the purposes of providing clinical research definitions of severe and early onset pre-eclampsia that will hopefully be accepted in the international literature. Copyright © 2012 International Society for the Study of Hypertension in Pregnancy. All rights reserved.

  15. Postpartum Circulating Markers of Inflammation and the Systemic Acute-Phase Response After Early-Onset Preeclampsia.

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    van Rijn, Bas B; Bruinse, Hein W; Veerbeek, Jan H; Post Uiterweer, Emiel D; Koenen, Steven V; van der Bom, Johanna G; Rijkers, Ger T; Roest, Mark; Franx, Arie

    2016-02-01

    Preeclampsia is an inflammatory-mediated hypertensive disorder of pregnancy and seems to be an early indicator of increased cardiovascular risk, but mechanisms underlying this association are unclear. In this study, we identified levels of circulating inflammatory markers and dynamic changes in the systemic acute-phase response in 44 women with a history of severe early-onset preeclampsia, compared with 29 controls with only uneventful pregnancies at 1.5 to 3.5 years postpartum. Models used were in vivo seasonal influenza vaccination and in vitro whole-blood culture with T-cell stimulants and the toll-like receptor-4 ligand lipopolysaccharide. Outcome measures were C-reactive protein, interleukin-6 (IL-6), IL-18, fibrinogen, myeloperoxidase, and a panel of 13 cytokines representative of the innate and adaptive inflammatory response, in addition to established cardiovascular markers. The in vivo acute-phase response was higher for women with previous preeclampsia than that for controls without such a history, although only significant for C-reactive protein (P=0.04). Preeclampsia was associated with higher IL-1β (Ppreeclampsia: an adaptive response cluster associated with increased C-reactive protein and IL-6 before and after vaccination, increased weight, and low high-density lipoprotein cholesterol; and a toll-like receptor-4 mediated the cluster associated with increased IL-18 before and after vaccination but not associated with other cardiovascular markers. Furthermore, we found interactions between previous preeclampsia, common TLR4 gene variants, and the IL-18 response to vaccination. In conclusion, preeclampsia is associated with alterations in the inflammatory response postpartum mostly independent of other established cardiovascular risk markers. © 2015 American Heart Association, Inc.

  16. Quantification of Maternal Serum Cell-Free Fetal DNA in Early-Onset Preeclampsia

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    Mulan Ren

    2013-04-01

    Full Text Available The aim of this study was to determine whether the increased serum cell-free fetal DNA (cffDNA level of gravidas developed into early-onset preeclampsia (EOPE subsequently in the early second trimesters is related to prenatal screening markers. Serum was collected from 1011 gravidas. The level of cffDNA and prenatal screening markers were analyzed in 20 cases with EOPE and 20 controls. All fetuses were male. The maternal serum cffDNA level was assessed by amplification of the Y chromosome specific gene. Correlations between the variables were examined. (Logged cffDNA in EOPE (median, 3.08; interquartile range, 2.93–3.68 was higher than controls (median, 1.79; interquartile range, 1.46–2.53. The increased level of (logged cffDNA was correlated significantly with the increased human chorionic gonadotropin (HCG level (r = 0.628, p < 0.001. Significant reciprocal correlations between cffDNA and babies’ birth weight as well as gestation weeks at delivery were noted (r = −0.516, p = 0.001; r = −0.623, p < 0.001, respectively. The sensitivity and specificity of cffDNA to discriminate between the EOPE cases and the controls were 90% and 85%, respectively. CffDNA is a potential marker for EOPE, which had a significant reciprocal correlation with babies’ birth weight and gestation weeks at delivery. Moreover, it may help in indicating the underlying hypoxic condition in the placenta.

  17. New Predictive Model at 11+0 to 13+6 Gestational Weeks for Early-Onset Preeclampsia With Fetal Growth Restriction.

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    Chang, Ying; Chen, Xu; Cui, Hong-Yan; Li, Xing; Xu, Ya-Ling

    2017-05-01

    The aim of the present study was to determine a predictive model for early-onset preeclampsia with fetal growth restriction (FGR) to be used at 11 +0 to 13 +6 gestational weeks, by combining the maternal serum level of pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PLGF), placental protein 13 (PP13), soluble endoglin (sEng), mean arterial pressure (MAP), and uterine artery Doppler. This was a retrospective cohort study of 4453 pregnant women. Uterine artery Doppler examination was conducted in the first trimester. Maternal serum PAPP-A, PLGF, PP13, and sEng were measured. Mean arterial pressure was obtained. Women were classified as with/without early-onset preeclampsia, and women with preeclampsia were classified as with/without FGR. Receiver operating characteristic analysis was performed to determine the value of the model. There were 30 and 32 pregnant women with early-onset preeclampsia with and without FGR. The diagnosis rate of early-onset preeclampsia with FGR was 67.4% using the predictive model when the false positive rate was set at 5% and 73.2% when the false positive rate was 10%. The predictive model (MAP, uterine artery Doppler measurements, and serum biomarkers) had some predictive value for the early diagnosis (11 +0 to 13 +6 gestational weeks) of early-onset preeclampsia with FGR.

  18. Gene expression profiling reveals different molecular patterns in G-protein coupled receptor signaling pathways between early- and late-onset preeclampsia.

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    Liang, Mengmeng; Niu, Jianmin; Zhang, Liang; Deng, Hua; Ma, Jian; Zhou, Weiping; Duan, Dongmei; Zhou, Yuheng; Xu, Huikun; Chen, Longding

    2016-04-01

    Early-onset preeclampsia and late-onset preeclampsia have been regarded as two different phenotypes with heterogeneous manifestations; To gain insights into the pathogenesis of the two traits, we analyzed the gene expression profiles in preeclamptic placentas. A whole genome-wide microarray was used to determine the gene expression profiles in placental tissues from patients with early-onset (n = 7; 36 weeks) preeclampsia and their controls who delivered preterm (n = 5; 36 weeks). Genes were termed differentially expressed if they showed a fold-change ≥ 2 and q-value preeclampsia (177 genes were up-regulated and 450 were down-regulated). Gene ontology analysis identified significant alterations in several biological processes; the top two were immune response and cell surface receptor linked signal transduction. Among the cell surface receptor linked signal transduction-related, differentially expressed genes, those involved in the G-protein coupled receptor protein signaling pathway were significantly enriched. G-protein coupled receptor signaling pathway related genes, such as GPR124 and MRGPRF, were both found to be down-regulated in early-onset preeclampsia. The results were consistent with those of western blotting that the abundance of GPR124 was lower in early-onset compared with late-onset preeclampsia. The different gene expression profiles reflect the different levels of transcription regulation between the two conditions and supported the hypothesis that they are separate disease entities. Moreover, the G-protein coupled receptor signaling pathway related genes may contribute to the mechanism underlying early- and late-onset preeclampsia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Expression of MicroRNA-146a and MicroRNA-155 in Placental Villi in Early- and Late-Onset Preeclampsia.

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    Nizyaeva, N V; Kulikova, G V; Nagovitsyna, M N; Kan, N E; Prozorovskaya, K N; Shchegolev, A I; Sukhikh, G T

    2017-07-01

    We studied the expression of microRNA-146a and microRNA-155 in placental villi from 18 women (26-39 weeks of gestation) of reproductive age with early- or late-onset preeclampsia. The reference group consisted of women with physiological pregnancy and full-term gestation and with preterm birth after caesarian section on gestation week 26-31. MicroRNA-146a and microRNA-155 were detected by in situ hybridization with digoxigenin on paraffin sections. It was found that the expression of microRNA-146a in both syncytiotrophoblast of the intermediate villi and syncytial knots was lower at late-onset preeclampsia than at physiologic pregnancy of full-term period (p=0.037 and p=0.001 respectively). The expression of microRNA-155 in syncytiotrophoblast of intermediate placental villi in early-onset preeclampsia was higher than in group with preterm delivery (p=0.003). However, in syncytiotrophoblast of intermediate villi and in syncytial knots, the expression of microRNA-155 was lower at late-onset preeclampsia in comparison with full-term physiological pregnancy (p=0.005). In addition, the expression of microRNA-146a and microRNA-155 did not increase in the later terms in preeclampsia, while in the reference groups demonstrating gradual increase in the expression of these markers with increasing gestational age. Expression microRNA-146a and microRNA-155 little differed in early- and late-onset preeclampsia. These findings suggest that different variants of preeclampsia are probably characterized by common pathogenetic pathways. Damaged trophoblast cannot maintain of microRNAs synthesis at the required level, which determines the formation of a vicious circle in preeclampsia and further progression of the disease.

  20. Is Fetal Growth Restriction Associated with a More Severe Maternal Phenotype in the Setting of Early Onset Pre-Eclampsia? A Retrospective Study

    Science.gov (United States)

    Weiler, Jane; Tong, Stephen; Palmer, Kirsten R.

    2011-01-01

    Background Both pre-eclampsia and fetal growth restriction are thought to result from abnormal placental implantation in early pregnancy. Consistent with this shared pathophysiology, it is not uncommon to see growth restriction further confound the course of pre-eclampsia and vice versa. It has been previously suggested that superimposed growth restriction is associated with a more severe pre-eclamptic phenotype, however this has not been a consistent finding. Therefore, we set out to determine whether the presence of fetal growth restriction among women with severe early-onset pre-eclampsia was associated with more severe maternal disease compared to those without a growth-restricted fetus. Methods and Findings We undertook a retrospective cohort study of women presenting to a tertiary hospital with severe early-onset pre-eclampsia (restriction. However, no significant difference was seen in relation to the severity of pre-eclampsia between those with or without a growth-restricted baby. The presence of concomitant growth restriction was however associated with a significantly increased risk of stillbirth (p = 0.003) and total perinatal mortality (p = 0.02). Conclusions The presence of fetal growth restriction among women with severe early-onset pre-eclampsia is not associated with increased severity of maternal disease. However the incidence of stillbirth and perinatal death is significantly increased in this sub-population. PMID:22046419

  1. Protective Role of Maternal P.VAL158MET Catechol-O-methyltransferase Polymorphism against Early-Onset Preeclampsia and its Complications

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    Krnjeta Tijana

    2016-09-01

    Full Text Available Background: Up until now there have been contradictory data about the association between p.Val158Met catechol-O-methyltransferase (COMT polymorphism and risk of preeclampsia (PE. The goal of this study was to assess the potential correlation between p.Val158Met COMT polymorphism and risk of early-onset PE, risk of a severe form of early-onset PE, as well as risk of small-for-gestationalage (SGA complicating PE.

  2. Triggers for Preeclampsia Onset: a Case-Crossover Study.

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    Ford, Jane B; Schemann, Kathrin; Patterson, Jillian A; Morris, Jonathan; Herbert, Robert D; Roberts, Christine L

    2016-11-01

    Risk factors for preeclampsia are well established, whereas, the triggers associated with timing of preeclampsia onset are not. The aim of this study was to establish whether recent infection or other triggers were associated with timing of preeclampsia onset. We used a case-crossover design with preeclampsia cases serving as their own controls. Women with singleton pregnancies of ≥20 weeks gestation presenting at three hospitals were eligible for inclusion. Exposures to potential triggers were identified via guided questionnaire. Infective episodes included symptoms lasting >24 h. Preeclampsia was defined as hypertension (BP ≥140 mmHg and/or ≥90 mmHg) and proteinuria (protein/creatinine ratio ≥30 mg/mmol). Conditional logistic regression was used to compare the odds of exposure to potential triggers in the case windows (1-7 days preceding diagnosis of preeclampsia) and control windows (8-14 days prior to diagnosis); unadjusted odds ratios (ORs) are reported. Among 286 recruited women, 25 (8.7%) reported a new infection in the 7 days prior to preeclampsia onset and 21 (7.3%) in the 8-14 days prior. There was no significant association between onset of infection in the 7 days prior and preeclampsia diagnosis (OR 1.24, 95% CI 0.65, 2.34). Consumption of caffeine (OR 0.51, 95% CI 0.33, 0.77), spicy food (OR 0.49, 95% CI 0.30, 0.81), and alcohol (OR 0.26, 95% CI 0.10, 0.71) were strongly inversely associated with preeclampsia onset. Recent infection does not appear to trigger preeclampsia. Decreased consumption of caffeine, spicy food, and alcohol may be prodromal markers. Such behaviours may be early markers of imminent preeclampsia. © 2016 John Wiley & Sons Ltd.

  3. Altered hemodynamics and hyperuricemia accompany an elevated sFlt-1/PlGF ratio before the onset of early severe preeclampsia.

    LENUS (Irish Health Repository)

    Doherty, Anne

    2014-08-01

    Early identification of women at risk of developing early-onset severe preeclampsia (sPE) is a key objective in obstetrics. An elevated ratio of serum soluble fms-like tyrosine kinase (sFlt-1) to placenta-like growth factor (PlGF) (sFlt-1\\/PlGF ratio) precedes overt hypertension. The longitudinal relationship between this biomarker, maternal hemodynamics, and maternal serum uric acid during the pre-clinical phase is unknown.

  4. Maternal left ventricular hypertrophy and diastolic dysfunction and brain natriuretic peptide concentration in early- and late-onset pre-eclampsia.

    Science.gov (United States)

    Borges, V T M; Zanati, S G; Peraçoli, M T S; Poiati, J R; Romão-Veiga, M; Peraçoli, J C; Thilaganathan, B

    2018-04-01

    Pre-eclampsia (PE) is associated with maternal cardiac remodeling and diastolic dysfunction. The aim of this study was to assess and compare maternal left ventricular structure and diastolic function and levels of brain natriuretic peptide (BNP) in women with early-onset (< 34 weeks' gestation) vs those with late-onset (≥ 34 weeks' gestation) PE. This was a prospective, cross-sectional, observational study of 30 women with early-onset PE, 32 with late-onset PE and 23 normotensive controls. Maternal cardiac structure and diastolic function were assessed by echocardiography and plasma levels of BNP were measured by enzyme immunoassay. Early- and late-onset PE were associated with increased left ventricular mass index and relative wall thickness compared with normotensive controls. In women with early-onset PE, the prevalence of concentric hypertrophy (40%) and diastolic dysfunction (23%) was also significantly higher (both P < 0.05) compared with women with late-onset PE (16% for both). Maternal serum BNP levels were significantly higher (P < 0.05) in women with early-onset PE and correlated with relative wall thickness and left ventricular mass index. Early-onset PE is associated with more severe cardiac impairment than is late-onset PE, as evidenced by an increased prevalence of concentric hypertrophy, diastolic dysfunction and higher levels of BNP. These findings suggest that early-onset PE causes greater myocardial damage, increasing the risk of both peripartum and postpartum cardiovascular morbidity. Although these cardiovascular effects are easily identified by echocardiographic parameters and measuring BNP, further studies are needed to assess their clinical utility. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

  5. Maternal History and Uterine Artery Doppler in the Assessment of Risk for Development of Early- and Late-Onset Preeclampsia and Intrauterine Growth Restriction

    Directory of Open Access Journals (Sweden)

    Elisa Llurba

    2009-01-01

    Full Text Available Objective. To examine the value of one-step uterine artery Doppler at 20 weeks of gestation in the prediction pre-eclampsia (PE and/or intrauterine growth restriction (IUGR. Methods. A prospective multicentre study that included all women with singleton pregnancies at 19–22 weeks of gestation (w. The mean pulsatility index (mPI of both uterine arteries was calculated. Receiver-operating characteristics curves (ROC were drawn to compare uterine artery Doppler and maternal risk factors for the prediction of early-onset PE and/or IUGR (before 32 w and late-onset PE and/or IUGR. Results. 6,586 women were included in the study. Complete outcome data was recorded for 6,035 of these women (91.6%. PE developed in 75 (1.2% and IUGR in 69 (1.1% cases. Uterine Doppler mPI was 0.99 and the 90th centile was 1.40. For 10% false-positive rate, uterine Doppler mPI identified 70.6% of pregnancies that subsequently developed early-onset PE and 73.3% of pregnancies that developed early-onset IUGR. The test had a lower detection rate for the late-onset forms of the disease (23.5% for PE and 30% for IUGR. Maternal history has a low sensitivity in the detection of early-onset cases, although it is better at detecting late-onset PE. Conclusion. Uterine artery Doppler and maternal risk factors seem to select two different populations - early and late-onset PE which might suggest a different pathogenesis.

  6. [Effect of Low Molecular Weight Heparin Calcium Combined Compound Danshen Injection on Perinatal Outcomes of Nephrotic Syndrome Patients with Early Onset Severe Pre-eclampsia].

    Science.gov (United States)

    Tong, Chong-xin; Xing, Xiao-fen; Qiao, Shu-hua; Liu, Lin; Shan, Ling

    2015-08-01

    To observe the effect of low molecular weight heparin calcium (LMWHC) combined Compound Danshen Injection (DI) on nephrotic syndrome patients with early onset severe preeclampsia. Totally 80 nephrotic syndrome patients with early onset severe pre-eclampsia were randomly assigned to four groups voluntarily, i.e., Group A (22 cases, treated by magnesium sulfate), B (19 cases, treated by magnesium sulfate plus LMWHC), C (21 cases, magnesium sulfate plus DI), D (18 cases, magnesium sulfate plus LMWHC and DI). Umbilical arterial S/D ratios, amniotic fluid index (AFI), prolonged gestational age, placenta weight, neonatal weight, and Apgar score were compared among the four groups. Compared with before treatment in the same group, umbilical arterial S/D ratios decreased in the four groups (P <0. 05). AFI decreased in Group A, while it increased in Group B, C, and D (P<0. 05). Compared with Group A at the same time point, umbilical arterial S/D ratios decreased, and AFI increased in Group B, C, and D (P <0. 01 , P <0. 05). Prolonged gestational age and neonatal weight were increased in Group B, C, and D (P <0. 01, P <0. 05). Placenta weight were increased in Group B and D (P <0. 05). Apgar scores at 1 and 5 min were improved in Group D (P <0. 05). Compared with Group B and C at the same time point, umbilical arterial S/D ratios decreased, and AFI increased in Group D (P<0. 05). Compared with Group B, prolonged gestational age and placenta weight were decreased in Group C, but prolonged gestational age and placenta weight were increased in Group D (P <0.05). Compared with Group C, prolonged gestational age, placenta weight, and neonatal weight were increased in Group D (P <0. 05). Treatment of nephrotic syndrome patients with early onset severe pre-eclampsia by LMWHC combined DI could prolong gestational ages, obviously improve prenatal outcomes, with better effect obtained than using any of them alone.

  7. Plasma factors in severe early-onset preeclampsia do not substantially alter endothelial gene expression in vitro

    NARCIS (Netherlands)

    Donker, RB; Asgeirsdottir, SA; Gerbens, F; van Pamus, MG; Kallenberg, CGM; Meerman, GJT; Aarnoudse, JG; Molema, G

    OBJECTIVE: Systemic endothelial dysfunction is a central feature in the pathophysiology of preeclampsia. Its cell biologic and molecular basis is poorly understood. One leading hypothesis argues that endothelial dysfunction is caused by (at present largely unknown) circulating factors released from

  8. Proteomics Analysis Reveals Abnormal Electron Transport and Excessive Oxidative Stress Cause Mitochondrial Dysfunction in Placental Tissues of Early-Onset Preeclampsia.

    Science.gov (United States)

    Xu, Zhongwei; Jin, Xiaohan; Cai, Wei; Zhou, Maobin; Shao, Ping; Yang, Zhen; Fu, Rong; Cao, Jin; Liu, Yan; Yu, Fang; Fan, Rong; Zhang, Yan; Zou, Shuang; Zhou, Xin; Yang, Ning; Chen, Xu; Li, Yuming

    2018-04-20

    Early-onset preeclampsia (EOS-PE) refers to preeclampsia that occurred before 34 gestation weeks. This study was conducted to explore the relationship between mitochondrial dysfunction and the pathogenesis of EOS-PE using proteomic strategy. To identify altering expressed mitochondrial proteins between severe EOS-PE and healthy pregnancies, enrichment of mitochondria coupled with iTRAQ-based quantitative proteomic method was performed. IHC and western blot were performed to detect the alteration of changing expression proteins, and confirmed the accuracy of proteomic results. We totally quantified 1372 proteins and screened 132 altering expressed mitochondrial proteins, including 86 down-regulated expression proteins and 46 up-regulated expression proteins (pelectron transport chain and oxidative phosphorylation. Especially, mitochondrial related molecules, PRDX2, PARK7, BNIP3, BCL2, PDHA1, SUCLG1, ACADM and NDUFV1, were involved in energy production process in the matrix and membrane of mitochondria. Our results showed that abnormal electron transport, excessive oxidative stress and mitochondrion disassembly might be the main cause of mitochondrial dysfunction, and was related to the pathogenesis of EOS-PE. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  9. Women with a recent history of early-onset pre-eclampsia have a worse periodontal condition

    NARCIS (Netherlands)

    Kunnen, Alina; Blaauw, Judith; van Doormaal, Jasper J.; van Pampus, Maria G; van der Schans, Cees; Aarnoudse, Jan G; van Winkelhoff, Arie J; Abbas, Frank

    OBJECTIVE: Pre-eclampsia is a complication of pregnancy characterized by systemic vascular dysfunction and pathological changes in placental arteries. Growing evidence of chronic infection as an aetiological factor in vascular diseases prompted us to study maternal periodontal disease in subjects

  10. Women with a recent history of early-onset pre-eclampsia have a worse periodontal condition

    NARCIS (Netherlands)

    Kunnen, Alina; Blaauw, Judith; van Doormaal, Jasper J.; van Pampus, Maria G.; van der Schans, Cees P.; Aarnoudse, Jan G.; van Winkelhoff, Arie J.; Abbas, Frank

    Objective: Pre-eclampsia is a complication of pregnancy characterized by systemic vascular dysfunction and pathological changes in placental arteries. Growing evidence of chronic infection as an aetiological factor in vascular diseases prompted us to study maternal periodontal disease in subjects

  11. Angiogenic Factor Profiles in Pregnant Women With a History of Early-Onset Severe Preeclampsia Receiving Low-Molecular-Weight Heparin Prophylaxis.

    Science.gov (United States)

    Lecarpentier, Edouard; Gris, Jean Christophe; Cochery-Nouvellon, Eva; Mercier, Erick; Touboul, Cyril; Thadhani, Ravi; Karumanchi, S Ananth; Haddad, Bassam

    2018-01-01

    To evaluate whether daily low-molecular-weight (LMW) heparin prophylaxis during pregnancy alters profile of circulating angiogenic factors that have been linked with the pathogenesis of preeclampsia and fetal growth restriction. This is a planned ancillary study of the Heparin-Preeclampsia trial, a randomized trial in pregnant women with a history of severe early-onset preeclampsia (less than 34 weeks of gestation). In the parent study, all women were treated with aspirin and then randomized to receive LMW heparin or aspirin alone. In this study, we measured serum levels of circulating angiogenic factors (soluble fms-like tyrosine kinase-1, placental growth factor, and soluble endoglin by immunoassay) at the following gestational windows: 10-13 6/7 weeks, 14-17 6/7 weeks, 18-21 6/7 weeks, 22-25 6/7 weeks, 26-29 6/7 weeks, 30-33 6/7 weeks, and 34-37 6/7 weeks. Samples were available from 185 patients: LMW heparin+aspirin (n=92) and aspirin alone (n=93). The two groups had comparable baseline characteristics and had similar adverse composite outcomes (35/92 [38.0%] compared with 36/93 [38.7%]; P=.92). There were no significant differences in serum levels of soluble fms-like tyrosine kinase-1, placental growth factor, and soluble endoglin in the participants who received LMW heparin and aspirin compared with those who received aspirin alone regardless of gestational age period. Finally, women who developed an adverse composite outcome at less than 34 weeks of gestation demonstrated significant alterations in serum angiogenic profile as early as 10-13 6/7 weeks that was most dramatic 6-8 weeks preceding delivery. Prophylactic LMW heparin therapy when beginning from before 14 weeks of gestation with aspirin during pregnancy is not associated with an improved angiogenic profile. This may provide a molecular explanation for the lack of clinical benefit noted in recent trials. ClinicalTrials.gov, NCT00986765.

  12. Evaluation of maternal serum hypoxia inducible factor-1α, progranulin and syndecan-1 levels in pregnancies with early- and late-onset preeclampsia.

    Science.gov (United States)

    Alici Davutoğlu, Ebru; Akkaya Firat, Asuman; Ozel, Ayşegül; Yılmaz, Nevin; Uzun, Isil; Temel Yuksel, Ilkbal; Madazlı, Riza

    2018-08-01

    To determine the serum levels of HIF-1 α, progranulin, and syndecan-1 in preeclampsia (PE) and normal pregnancy, and to compare whether these markers demonstrate any difference between early-onset PE (EO-PE) and late-onset PE (LO-PE). This cross-sectional study was conducted on 27 women with EO-PE, 27 women with LO-PE, and 26 healthy normotensive pregnant controls matched for gestational age. Maternal levels of serum HIF-1 α, progranulin, and syndecan-1 were measured with the use of an enzyme-linked immunosorbent assay kit. Statistical analysis revealed significant differences between the control and the PE groups in progranulin (p progranulin levels were significantly higher in LO-PE compared with the other two groups (EO-PE versus LO-PE and LO-PE versus controls p = .000). Control group presented significantly higher syndecan-1 levels, than EO and LO-PE (p progranulin levels (r = .439, p= .000). Serum progranulin may have potential to be used as a biomarker for the differentiation of EO-PE and LO-PE. The co-operative action between HIF-1 α and progranulin might play a key role in the pathogenesis of LO-PE. The predominant feature of LO-PE seems to be an inflammatory process, whereas in EO-PE placentation problem seems to be the main pathology.

  13. Differences in clinical presentation and pregnancy outcomes in antepartum preeclampsia and new-onset postpartum preeclampsia: Are these the same disorder?

    Science.gov (United States)

    Vilchez, Gustavo; Hoyos, Luis R; Leon-Peters, Jocelyn; Lagos, Moraima; Argoti, Pedro

    2016-11-01

    New-onset postpartum preeclampsia is a poorly defined condition that accounts for a significant percentage of eclampsia cases. It is unclear whether new-onset postpartum preeclampsia is a different disorder from or belongs to the same spectrum of classic antepartum preeclampsia. The objective of this study was to compare the clinical presentation and pregnancy outcomes of antepartum preeclampsia and new-onset postpartum preeclampsia. A retrospective study including 92 patients with antepartum preeclampsia and 92 patients with new-onset postpartum preeclampsia was performed. Clinical presentation and pregnancy outcomes were compared. Chi-square test was used to analyze categorical variables, and independent t -test and Mann-Whitney U -test for numerical variables. P -values of presentation, laboratory markers and pregnancy outcomes. New-onset postpartum preeclampsia has a distinct patient profile and clinical presentation than antepartum preeclampsia, suggesting they may represent different disorders. Characterization of a patient profile with increased risk of developing this condition will help clinicians to identify patients at risk and provide early and targeted interventions to decrease the morbidity associated with this condition.

  14. Relationship between histopathological changes in post partum renal biopsies and renal function tests of African women with early onset pre-eclampsia.

    Science.gov (United States)

    Khedun, S M; Naicker, T; Moodley, J

    2000-05-01

    To improve the diagnostic accuracy of concurrent renal disease in hypertension of pregnancy, biopsy evaluation is essential. In addition, establishing underlying renal disease is important for prognosis on future pregnancies. We therefore designed a study to determine the diagnostic yield of postpartum renal biopsy and the nature and frequency of complications associated with this procedure. Also, to determine relationships, if any, between renal function tests and ultrastructural and histopathological findings. Fifty renal biopsies were performed in the immediate postpartum period in black African women with early onset pre-eclampsia. Each biopsy specimen was placed in a separate container and coded so that sampling was unknown to the electron microscopist. Each biopsy specimen was divided into three parts, and processed and stained for light, fluorescent and transmission electron microscopy using conventional techniques. Renal tissue biopsies were adequate for diagnostic purposes in all cases. There were no complications in any of the 50 patients studied. Ultrastructural examination confirmed the light microscopy findings. In addition the ultrastructural findings showed intramembranous deposits, foot process fusion and mesangial deposits. In 16 patients with normal renal function tests; the biopsies evaluation from these patients showed ultrastructural changes. In the remaining 34 patients with abnormal renal function tests of varying severity; biopsy evaluation from these patients showed both ultrastructural and histopathological changes. Renal biopsy procedure is safe, and ultrastructural and histological findings obtained from postpartum renal biopsies are more informative than the routine renal function tests.

  15. An analysis of the differences between early and late preeclampsia with severe hypertension.

    Science.gov (United States)

    Li, X L; Guo, P L; Xue, Y; Gou, W L; Tong, M; Chen, Q

    2016-01-01

    Preeclampsia is clinically divided into early onset and late onset preeclampsia based on the gestational age at delivery. Although the diagnostic criteria are the same in each subgroup of preeclampsia, it has been suggested that the maternal and perinatal mortalities of early onset and late onset preeclampsia are different. However, studies that compare clinical parameters or laboratory biomarkers between early onset and late onset preeclampsia are limited. Data on 177 women with early or late preeclampsia with severe hypertension were collected from a University Teaching Hospital from January 2010 to January 2011 and analysed. Data included all the clinical parameters and laboratory biomarkers of liver and renal function. 63 women and 114 women were diagnosed with early and late preeclampsia with severe hypertension, respectively. There was no difference in the maternal age and the incidence of clinical symptoms including edema, vision disturbance, severe headache and stillbirth between two groups. There was a decrease in alkaline phosphatase levels in early preeclampsia with severe hypertension but other markers of liver function were not altered. However, renal function including blood urea nitrogen, creatinine and uric acid were significantly higher in early preeclampsia with severe hypertension. Umbilical artery systolic velocity/diastolic velocity ratio was significantly higher in early preeclampsia with severe hypertension. Our data demonstrates that the laboratory biomarkers of renal function differ between early and late preeclampsia with severe hypertension. The severity of renal dysfunction correlated with the time of delivery in preeclampsia with severe hypertension. Copyright © 2015 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

  16. Late onset postpartum preeclampsia 3 months after delivery.

    Science.gov (United States)

    Giwa, Al; Nguyen, Melissa

    2017-10-01

    Preeclampsia is defined by the American College of Obstetrics and Gynecology (ACOG) as "the occurrence of new onset hypertension plus new-onset proteinuria" [1]. Up-to-Date elaborates a little further on this by defining preeclampsia as "the new onset of hypertension and proteinuria, or hypertension and end-organ dysfunction with or without proteinuria, after 20 weeks of gestation in a previously normotensive woman. It may also develop postpartum. Severe hypertension or signs/symptoms of end-organ injury represent the severe end of the disease spectrum" [2] In 2013, the American College of Obstetricians and Gynecologists removed proteinuria as a key component in the diagnosis of preeclampsia. They also removed massive proteinuria (previously, 5 g/24 hours) and fetal growth restriction as possible features of severe disease. They found that were was a poor correlation in many outcomes between massive proteinuria and fetal growth restriction when managed similarly, with or without preeclampsia as a diagnosis. Oliguria was also removed as a characteristic of severe disease. [3] There have been several cases reported in the literature as well as by Obstetricians citing the incidence of preeclampsia occurring upwards of 6 to even 12 weeks postpartum. We hope to demonstrate what we believe to be a case of postpartum preeclampsia at 89 days postpartum. Published by Elsevier Inc.

  17. The prediction of late-onset preeclampsia: Results from a longitudinal proteomics study.

    Science.gov (United States)

    Erez, Offer; Romero, Roberto; Maymon, Eli; Chaemsaithong, Piya; Done, Bogdan; Pacora, Percy; Panaitescu, Bogdan; Chaiworapongsa, Tinnakorn; Hassan, Sonia S; Tarca, Adi L

    2017-01-01

    Late-onset preeclampsia is the most prevalent phenotype of this syndrome; nevertheless, only a few biomarkers for its early diagnosis have been reported. We sought to correct this deficiency using a high through-put proteomic platform. A case-control longitudinal study was conducted, including 90 patients with normal pregnancies and 76 patients with late-onset preeclampsia (diagnosed at ≥34 weeks of gestation). Maternal plasma samples were collected throughout gestation (normal pregnancy: 2-6 samples per patient, median of 2; late-onset preeclampsia: 2-6, median of 5). The abundance of 1,125 proteins was measured using an aptamers-based proteomics technique. Protein abundance in normal pregnancies was modeled using linear mixed-effects models to estimate mean abundance as a function of gestational age. Data was then expressed as multiples of-the-mean (MoM) values in normal pregnancies. Multi-marker prediction models were built using data from one of five gestational age intervals (8-16, 16.1-22, 22.1-28, 28.1-32, 32.1-36 weeks of gestation). The predictive performance of the best combination of proteins was compared to placental growth factor (PIGF) using bootstrap. 1) At 8-16 weeks of gestation, the best prediction model included only one protein, matrix metalloproteinase 7 (MMP-7), that had a sensitivity of 69% at a false positive rate (FPR) of 20% (AUC = 0.76); 2) at 16.1-22 weeks of gestation, MMP-7 was the single best predictor of late-onset preeclampsia with a sensitivity of 70% at a FPR of 20% (AUC = 0.82); 3) after 22 weeks of gestation, PlGF was the best predictor of late-onset preeclampsia, identifying 1/3 to 1/2 of the patients destined to develop this syndrome (FPR = 20%); 4) 36 proteins were associated with late-onset preeclampsia in at least one interval of gestation (after adjustment for covariates); 5) several biological processes, such as positive regulation of vascular endothelial growth factor receptor signaling pathway, were perturbed; and 6

  18. The prediction of late-onset preeclampsia: Results from a longitudinal proteomics study

    Science.gov (United States)

    Erez, Offer; Romero, Roberto; Maymon, Eli; Chaemsaithong, Piya; Done, Bogdan; Pacora, Percy; Panaitescu, Bogdan; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.

    2017-01-01

    Background Late-onset preeclampsia is the most prevalent phenotype of this syndrome; nevertheless, only a few biomarkers for its early diagnosis have been reported. We sought to correct this deficiency using a high through-put proteomic platform. Methods A case-control longitudinal study was conducted, including 90 patients with normal pregnancies and 76 patients with late-onset preeclampsia (diagnosed at ≥34 weeks of gestation). Maternal plasma samples were collected throughout gestation (normal pregnancy: 2–6 samples per patient, median of 2; late-onset preeclampsia: 2–6, median of 5). The abundance of 1,125 proteins was measured using an aptamers-based proteomics technique. Protein abundance in normal pregnancies was modeled using linear mixed-effects models to estimate mean abundance as a function of gestational age. Data was then expressed as multiples of-the-mean (MoM) values in normal pregnancies. Multi-marker prediction models were built using data from one of five gestational age intervals (8–16, 16.1–22, 22.1–28, 28.1–32, 32.1–36 weeks of gestation). The predictive performance of the best combination of proteins was compared to placental growth factor (PIGF) using bootstrap. Results 1) At 8–16 weeks of gestation, the best prediction model included only one protein, matrix metalloproteinase 7 (MMP-7), that had a sensitivity of 69% at a false positive rate (FPR) of 20% (AUC = 0.76); 2) at 16.1–22 weeks of gestation, MMP-7 was the single best predictor of late-onset preeclampsia with a sensitivity of 70% at a FPR of 20% (AUC = 0.82); 3) after 22 weeks of gestation, PlGF was the best predictor of late-onset preeclampsia, identifying 1/3 to 1/2 of the patients destined to develop this syndrome (FPR = 20%); 4) 36 proteins were associated with late-onset preeclampsia in at least one interval of gestation (after adjustment for covariates); 5) several biological processes, such as positive regulation of vascular endothelial growth factor

  19. Low-molecular-weight heparin added to aspirin in the prevention of recurrent early-onset pre-eclampsia in women with inheritable thrombophilia : the FRUIT-RCT

    NARCIS (Netherlands)

    De Vries, J. I. P.; Van Pampus, M. G.; Hague, W. M.; Bezemer, P. D.; Joosten, J. H.

    Background: Early-onset hypertensive disorders (HD) of pregnancy and small-for-gestational age infants (SGA) are associated with placental vascular thrombosis, these often recur and are also associated with inheritable thrombophilia. Aspirin reduces the recurrence risk. Objectives: Adding

  20. Robust early pregnancy prediction of later preeclampsia using metabolomic biomarkers.

    LENUS (Irish Health Repository)

    Kenny, Louise C

    2012-01-31

    Preeclampsia is a pregnancy-specific syndrome that causes substantial maternal and fetal morbidity and mortality. The etiology is incompletely understood, and there is no clinically useful screening test. Current metabolomic technologies have allowed the establishment of metabolic signatures of preeclampsia in early pregnancy. Here, a 2-phase discovery\\/validation metabolic profiling study was performed. In the discovery phase, a nested case-control study was designed, using samples obtained at 15+\\/-1 weeks\\' gestation from 60 women who subsequently developed preeclampsia and 60 controls taking part in the prospective Screening for Pregnancy Endpoints cohort study. Controls were proportionally population matched for age, ethnicity, and body mass index at booking. Plasma samples were analyzed using ultra performance liquid chromatography-mass spectrometry. A multivariate predictive model combining 14 metabolites gave an odds ratio for developing preeclampsia of 36 (95% CI: 12 to 108), with an area under the receiver operator characteristic curve of 0.94. These findings were then validated using an independent case-control study on plasma obtained at 15+\\/-1 weeks from 39 women who subsequently developed preeclampsia and 40 similarly matched controls from a participating center in a different country. The same 14 metabolites produced an odds ratio of 23 (95% CI: 7 to 73) with an area under receiver operator characteristic curve of 0.92. The finding of a consistent discriminatory metabolite signature in early pregnancy plasma preceding the onset of preeclampsia offers insight into disease pathogenesis and offers the tantalizing promise of a robust presymptomatic screening test.

  1. Robust Early Pregnancy Prediction of Later Preeclampsia Using Metabolomic Biomarkers.

    LENUS (Irish Health Repository)

    Kenny, Louise C

    2010-09-13

    Preeclampsia is a pregnancy-specific syndrome that causes substantial maternal and fetal morbidity and mortality. The etiology is incompletely understood, and there is no clinically useful screening test. Current metabolomic technologies have allowed the establishment of metabolic signatures of preeclampsia in early pregnancy. Here, a 2-phase discovery\\/validation metabolic profiling study was performed. In the discovery phase, a nested case-control study was designed, using samples obtained at 15±1 weeks\\' gestation from 60 women who subsequently developed preeclampsia and 60 controls taking part in the prospective Screening for Pregnancy Endpoints cohort study. Controls were proportionally population matched for age, ethnicity, and body mass index at booking. Plasma samples were analyzed using ultra performance liquid chromatography-mass spectrometry. A multivariate predictive model combining 14 metabolites gave an odds ratio for developing preeclampsia of 36 (95% CI: 12 to 108), with an area under the receiver operator characteristic curve of 0.94. These findings were then validated using an independent case-control study on plasma obtained at 15±1 weeks from 39 women who subsequently developed preeclampsia and 40 similarly matched controls from a participating center in a different country. The same 14 metabolites produced an odds ratio of 23 (95% CI: 7 to 73) with an area under receiver operator characteristic curve of 0.92. The finding of a consistent discriminatory metabolite signature in early pregnancy plasma preceding the onset of preeclampsia offers insight into disease pathogenesis and offers the tantalizing promise of a robust presymptomatic screening test.

  2. Differential Proteomic Analysis of Syncytiotrophoblast Extracellular Vesicles from Early-Onset Severe Preeclampsia, using 8-Plex iTRAQ Labeling Coupled with 2D Nano LC-MS/MS

    Directory of Open Access Journals (Sweden)

    Hongmei Li

    2015-06-01

    Full Text Available Aims: Previous studies have revealed that the increased shedding of syncytiotrophoblast extracellular vesicles (STBM may lead to preeclampsia (PE. We aimed to identify the proteins carried by STBM and their potential pathological roles in early-onset severe PE. Methods: In this study, we performed a differential proteomic analysis of STBM from early-onset severe PE patients, using iTRAQ isobaric tags and 2D nano LC-MS/MS. STBM were generated by the in vitro explant culture method, and then verified by electron microscopy and western blot analysis. Results: A total of 18 533 unique peptides and 3 317 proteins were identified, 3 292 proteins were quantified. We identified 194 differentially expressed proteins in STBM from early-onset severe PE patients, 122 proteins were up-regulated and 72 proteins were down-regulated. Further bioinformatics analysis revealed that mitochondrion, transmembrane transport and transmembrane transporter activity were the most abundant categories in gene ontology (GO annotation. Glycolysis/ gluconeogenesis, citrate cycle, fatty acid elongation, steroid hormone biosynthesis and oxidative phosphorylation were the five significantly represented pathways. Four differentially expressed proteins (siglec-6, calnexin, CD63 and S100-A8 related to inflammation, coagulation or immunoregulation were independently verified using western blot. Conclusions: The identification of key proteins carried by STBM may serve not only as a basis for better understanding and further exploring the etiology and pathogenesis of PE, but also as potential biomarkers and in providing targets for future therapy in PE, especially in early-onset severe PE(sPE.

  3. Risk factors for new-onset late postpartum preeclampsia in women without a history of preeclampsia.

    Science.gov (United States)

    Bigelow, Catherine A; Pereira, Guilherme A; Warmsley, Amber; Cohen, Jennifer; Getrajdman, Chloe; Moshier, Erin; Paris, Julia; Bianco, Angela; Factor, Stephanie H; Stone, Joanne

    2014-04-01

    Risk factors for the development of new-onset late postpartum preeclampsia (LPP) in women without any history of preeclampsia are not known. Because identification of women who are at risk may lead to an earlier diagnosis of disease and improved maternal outcomes, this study identified risk factors (associated patient characteristics) for new-onset LPP. A case-control study of 34 women with new-onset LPP and 68 women without new-onset LPP after normal delivery, who were matched on date of delivery, was conducted at Mount Sinai Hospital, New York, NY. Data were collected by chart review. Exact conditional logistic regression identified patient characteristics that were associated with new-onset LPP. New-onset LPP was associated with age ≥40 years (adjusted odds ratio, 24.83; 95% confidence interval [CI], 1.43-infinity; P = .03), black race (adjusted odds ratio, 78.35; 95% CI, 7.25-infinity; P infinity; P = .001), final pregnancy body mass index of ≥30 kg/m(2) (adjusted odds ratio, 13.38; 95% CI, 1.87-infinity; P = .01), and gestational diabetes mellitus (adjusted odds ratio, 72.91; 95% CI, 5.52-infinity; P < .001). As predictive tests for new-onset LPP, the sensitivity and specificity of having ≥1 of these characteristics was 100% and 59%, respectively, and the sensitivity and specificity of having ≥2 was 56% and 93%, respectively. Older age, black race, Latino ethnicity, obesity, and a pregnancy complicated by gestational diabetes mellitus all are associated positively with the development of new-onset LPP. Closer observation may be warranted in these populations. Copyright © 2014 Mosby, Inc. All rights reserved.

  4. First-trimester screening for early and late preeclampsia using maternal characteristics, biomarkers, and estimated placental volume.

    Science.gov (United States)

    Sonek, Jiri; Krantz, David; Carmichael, Jon; Downing, Cathy; Jessup, Karen; Haidar, Ziad; Ho, Shannon; Hallahan, Terrence; Kliman, Harvey J; McKenna, David

    2018-01-01

    Preeclampsia is a major cause of perinatal morbidity and mortality. First-trimester screening has been shown to be effective in selecting patients at an increased risk for preeclampsia in some studies. We sought to evaluate the feasibility of screening for preeclampsia in the first trimester based on maternal characteristics, medical history, biomarkers, and placental volume. This is a prospective observational nonintervention cohort study in an unselected US population. Patients who presented for an ultrasound examination between 11-13+6 weeks' gestation were included. The following parameters were assessed and were used to calculate the risk of preeclampsia: maternal characteristics (demographic, anthropometric, and medical history), maternal biomarkers (mean arterial pressure, uterine artery pulsatility index, placental growth factor, pregnancy-associated plasma protein A, and maternal serum alpha-fetoprotein), and estimated placental volume. After delivery, medical records were searched for the diagnosis of preeclampsia. Detection rates for early-onset preeclampsia (preeclampsia (≥34 weeks' gestation) for 5% and 10% false-positive rates using various combinations of markers were calculated. We screened 1288 patients of whom 1068 (82.99%) were available for analysis. In all, 46 (4.3%) developed preeclampsia, with 13 (1.22%) having early-onset preeclampsia and 33 (3.09%) having late-onset preeclampsia. Using maternal characteristics, serum biomarkers, and uterine artery pulsatility index, the detection rate of early-onset preeclampsia for either 5% or 10% false-positive rate was 85%. With the same protocol, the detection rates for preeclampsia with delivery preeclampsia were 15% and 48% for 5% and 10%, while for preeclampsia at ≥37 weeks' gestation the detection rates were 24% and 43%, respectively. The detection rates for late-onset preeclampsia and preeclampsia with delivery at >37 weeks' gestation were not improved by the addition of biomarkers. Screening

  5. Low-molecular-weight heparin and aspirin in the prevention of recurrent early-onset pre-eclampsia in women with antiphospholipid antibodies : the FRUIT-RCT

    NARCIS (Netherlands)

    van Hoorn, Marion E.; Hague, William M.; Pampus , van Mariëlle G.; Bezemer, Dick; de Vries, Johanna I. P.

    Objective: To examine whether combined treatment with low-molecular-weight heparin (LMWH) and aspirin reduces recurrent hypertensive disorders of pregnancy (HD: pre-eclampsia, eclampsia or HELLP syndrome) in women with antiphospholipid antibodies (aPLA) and a previous delivery for HD and/or

  6. Early pre-eclampsia unmasks underlying IgA nephropathy

    Directory of Open Access Journals (Sweden)

    Mona Singh

    2010-12-01

    Full Text Available Mona Singh, Akhenaton Pappoe, Burl R DonDivision of Nephrology, University of California Davis Medical Center, Sacramento, CA, USAAbstract: Pre-eclampsia is the most ominous complication of pregnancy, and primary glomerular diseases can mimic pre-eclampsia in presentation. A patient presented at 21 weeks gestation with signs and symptoms of both pre-eclampsia and primary glomerular nephropathy. A critical clinical decision whether to continue or terminate the pregnancy was dependent on results of a renal biopsy. The biopsy noted the presence of both pre-eclampsia and immunoglobulin A (IgA nephropathy. Thus, the onset of pre-eclampsia unmasked the presence of unrecognized IgA nephropathy, and the IgA nephropathy was a risk factor for this patient developing pre-eclampsia. The results of a renal biopsy are key in distinguishing pre-eclampsia from other kidney diseases and instituting appropriate clinical management.Keywords: proteinuria, IgA nephropathy, renal biopsy, pre-eclampsia

  7. Angiogenic factors for prediction of preeclampsia and intrauterine growth restriction onset in high-risk women: AngioPred study.

    Science.gov (United States)

    Raia-Barjat, Tiphaine; Prieux, Carole; Gris, Jean-Christophe; Chapelle, Céline; Laporte, Silvy; Chauleur, Céline

    2017-09-22

    The study aimed to compare the level of two angiogenic factors, soluble fms-like tyrosine kinase-1 (sFlt1) and soluble endoglin (sEng), for the prediction of preeclampsia and intrauterine growth restriction in high-risk pregnant women. A prospective multicenter cohort study of 200 pregnant patients was conducted between June 2008 and October 2010. sFlt1 and sEng were measured by enzyme-linked immunosorbent assay. Forty-five patients developed a placenta-mediated adverse pregnancy outcome. Plasma levels of sFlt1 and sEng were higher in patients who will experience a preeclampsia at 28, 32, and 36 weeks compared with patients with no complication. The same results were observed for intrauterine growth restriction. Plasma levels of sFlt1 and sEng were not significantly different for patients with preeclampsia compare to patients with intrauterine growth restriction. Patients with early pre-eclampsia (PE) had very high rates of angiogenic factors at 20, 24, and 28 weeks. Patients with late PE and early and late intrauterine growth retardation (IUGR) had high rates at 32 and 36 weeks. In high-risk women, angiogenic factors are disturbed before the onset of preeclampsia and this is true for intrauterine growth restriction.

  8. Combined Screening for Early Detection of Pre-Eclampsia

    Directory of Open Access Journals (Sweden)

    Hee Jin Park

    2015-08-01

    Full Text Available Although the precise pathophysiology of pre-eclampsia remains unknown, this condition continues to be a major cause of maternal and fetal mortality. Early prediction of pre-eclampsia would allow for timely initiation of preventive therapy. A combination of biophysical and biochemical markers are superior to other tests for early prediction of the development of pre-eclampsia. Apart from the use of parameters in first-trimester aneuploidy screening, cell-free fetal DNA quantification is emerging as a promising marker for prediction of pre-eclampsia. This article reviews the current research of the most important strategies for prediction of pre-eclampsia, including the use of maternal risk factors, mean maternal arterial pressure, ultrasound parameters, and biomarkers.

  9. Early pregnancy vitamin D status and risk of preeclampsia.

    Science.gov (United States)

    Mirzakhani, Hooman; Litonjua, Augusto A; McElrath, Thomas F; O'Connor, George; Lee-Parritz, Aviva; Iverson, Ronald; Macones, George; Strunk, Robert C; Bacharier, Leonard B; Zeiger, Robert; Hollis, Bruce W; Handy, Diane E; Sharma, Amitabh; Laranjo, Nancy; Carey, Vincent; Qiu, Weilliang; Santolini, Marc; Liu, Shikang; Chhabra, Divya; Enquobahrie, Daniel A; Williams, Michelle A; Loscalzo, Joseph; Weiss, Scott T

    2016-12-01

    Low vitamin D status in pregnancy was proposed as a risk factor of preeclampsia. We assessed the effect of vitamin D supplementation (4,400 vs. 400 IU/day), initiated early in pregnancy (10-18 weeks), on the development of preeclampsia. The effects of serum vitamin D (25-hydroxyvitamin D [25OHD]) levels on preeclampsia incidence at trial entry and in the third trimester (32-38 weeks) were studied. We also conducted a nested case-control study of 157 women to investigate peripheral blood vitamin D-associated gene expression profiles at 10 to 18 weeks in 47 participants who developed preeclampsia. Of 881 women randomized, outcome data were available for 816, with 67 (8.2%) developing preeclampsia. There was no significant difference between treatment (N = 408) or control (N = 408) groups in the incidence of preeclampsia (8.08% vs. 8.33%, respectively; relative risk: 0.97; 95% CI, 0.61-1.53). However, in a cohort analysis and after adjustment for confounders, a significant effect of sufficient vitamin D status (25OHD ≥30 ng/ml) was observed in both early and late pregnancy compared with insufficient levels (25OHD preeclampsia (FDR preeclampsia incidence in the intention-to-treat paradigm. However, vitamin D levels of 30 ng/ml or higher at trial entry and in late pregnancy were associated with a lower risk of preeclampsia. Differentially expressed vitamin D-associated transcriptomes implicated the emergence of an early pregnancy, distinctive immune response in women who went on to develop preeclampsia. ClinicalTrials.gov NCT00920621. Quebec Breast Cancer Foundation and Genome Canada Innovation Network. This trial was funded by the National Heart, Lung, and Blood Institute. For details see Acknowledgments.

  10. Early-Onset Dementia

    DEFF Research Database (Denmark)

    Konijnenberg, Elles; Fereshtehnejad, Seyed-Mohammad; Kate, Mara Ten

    2017-01-01

    BACKGROUND: Early-onset dementia (EOD) is a rare condition, with an often atypical clinical presentation, and it may therefore be challenging to diagnose. Specialized memory clinics vary in the type of patients seen, diagnostic procedures applied, and the pharmacological treatment given. The aim...... of this study was to investigate quality-of-care indicators in subjects with EOD from 3 tertiary memory clinics in 3 European countries. METHODS: We included 1325 newly diagnosed EOD patients, ages 65 years or younger, between January 1, 2007 and December 31, 2013, from the Danish Dementia Registry...... (Rigshospitalet, Copenhagen), the Swedish Dementia Registry ("SveDem", Karolinska University Hospital, Stockholm), and the Amsterdam Dementia Cohort (VU University Medical Center). RESULTS: The frequency of EOD among all dementia patients was significantly lower in Copenhagen (410, 20%) and Stockholm (284, 21...

  11. A prospective cohort study on the clinical utility of second trimester mean arterial blood pressure in the prediction of late-onset preeclampsia among Nigerian women.

    Science.gov (United States)

    Udenze, I C; Arikawe, A P; Makwe, C C; Olowoselu, O F

    2017-06-01

    Early detection of preeclampsia will help reduce the morbidities and mortalities associated with the disorder. Late-onset preeclampsia was the predominant presentation in this cohort. The search for biomarkers for predicting preeclampsia is still ongoing. Mean arterial blood pressure (MABP), which has the advantage of presenting a single cutoff value compared with the use of systolic and diastolic blood pressure measurements, merits evaluation. The study aims to evaluate the clinical utility of second trimester MABP in the prediction of preeclampsia. This was a prospective cohort study of 155 normotensive, nonproteinuric pregnant women without prior history of gestational hypertension. The women were booked patients attending the antenatal clinic at the Lagos University Teaching Hospital and were all in their second trimesters of pregnancy. The outcome measures were systolic blood pressure, diastolic blood pressure, and MABP. The end point of the study was the development of preeclampsia. The diagnosis of preeclampsia was made by the attending obstetrician. The data were analyzed using the IBM SPSS statistical software. Statistical significance was set at P blood pressure, diastolic blood pressure, and MABP values in the group of women who later developed preeclampsia, P = 0.005, 0.001, and area under the receiver-operative characteristics curve (AUC) was 0.732 (95% confidence interval, 0.544-0.919, P = 0.011). The negative predictive value (NPV) was 88.88% and the positive predictive value (PPV) was 45.45%, P AUC of 0.732, MABP performed moderately (considering that excellent performance has an AUC of 1.0) in the prediction of late-onset preeclampsia in Nigerian women. Its high NPV suggests a strong ability to rule out preeclampsia and help to appropriate management.

  12. Early onset type 2 diabetes

    DEFF Research Database (Denmark)

    Bo, A; Thomsen, R W; Nielsen, J S

    2018-01-01

    was more frequent and meeting physical activity recommendations less likely in persons with early-onset type 2 DM. CONCLUSIONS: We found a clear age-gradient, with increasing prevalence of clinical and behavioural risk factors the younger the onset age of type 2 DM. Younger persons with early-onset type 2......AIM: To examine the association between early onset of type 2 diabetes (DM) and clinical and behavioural risk factors for later diabetes complications. METHODS: We conducted a cross-sectional study of 5115 persons with incident type 2 DM enrolled during 2010-2015 in the Danish Centre for Strategic...... Research in Type 2 Diabetes-cohort. We compared risk factors at time of diagnosis among those diagnosed at ≤45 years (early-onset) with diagnosis age 46-55, 56-65 (average-onset = reference), 66-75, and >75 years (late-onset). Prevalence ratios (PRs) were computed using Poisson regression. RESULTS: Poor...

  13. Genetics of preeclampsia: paradigm shifts

    NARCIS (Netherlands)

    Oudejans, Cees B. M.; van Dijk, Marie; Oosterkamp, Marjet; Lachmeijer, Augusta; Blankenstein, Marinus A.

    2007-01-01

    Segregation of preeclampsia into early-onset, placental and late-onset, maternal subtypes along with the acknowledgement of the contribution of epigenetics in placentally expressed genes proved to be a key first step in the identification of essential gene variants associated with preeclampsia.

  14. Preeclampsia

    Science.gov (United States)

    ... preeclampsia makes a woman a higher risk for future problems such as: Heart disease Diabetes Kidney disease ... medical problems in pregnancy. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 25th ed. Philadelphia, PA: ...

  15. ANALYSIS OF SERUM URIC ACID LEVELS IN EARLY SECOND TRIMESTER AS AN EARLY PREDICTOR FOR PREECLAMPSIA

    Directory of Open Access Journals (Sweden)

    Ratna Bulusu

    2017-01-01

    Full Text Available BACKGROUND Hypertensive disorders complicate 5-10% of all pregnancies. Screening for these factors in the second trimester of pregnancy will help in early detection of hypertensive disorders of pregnancy, thus enabling. 1. Early identification of patients at risk of developing preeclampsia and eclampsia. 2. Prophylactic medication to prevent hypertension or to reduce its severity. 3. Proper antenatal care. The aim of the study is to study the accuracy of serum uric acid levels in early second trimester (14-20 weeks as early predictor of preeclampsia. MATERIALS AND METHODS 100 pregnant normotensive women between 14-20 weeks gestation with singleton pregnancy irrespective of parity were selected randomly and serum levels of uric acid was estimated. Regular follow up of the cases was done till delivery. Number of cases developing preeclampsia was noted. Results were analysed statistically. RESULTS Out of the 100 patients enrolled in the study, 11 developed preeclampsia while rest 89 remained normotensive. Mean value of uric acid in preeclampsia cases was 6.28±0.86 mg/dL while that in normotensive cases was 3.42±0.94 mg/dL. This result was statistically significant. CONCLUSION Serum uric acid level at 14-20 weeks of gestation was significantly raised in the cases who developed preeclampsia as compared to those who remained normotensive. Hence, serum uric acid estimation at 14-20 weeks of gestation could be used as an effective parameter for predicting preeclampsia.

  16. Early onset sebaceous carcinoma

    Directory of Open Access Journals (Sweden)

    Kaltreider Sara A

    2011-09-01

    Full Text Available Abstract Background Ocular sebaceous carcinoma can masquerade as benign lesions resulting in delay of diagnosis. Early recognition is even more difficult in young patients where the disease rarely occurs. Here, we provide a clinicopathological correlation of ocular sebaceous carcinoma in a young individual lacking history of hereditary cancer or immunosuppression. Findings A detailed histopathological study including p53 DNA sequencing was performed on an aggressive sebaceous carcinoma presenting in a healthy 32 year-old Caucasian woman. She had no history of retinoblastoma, evidence for a hereditary cancer syndrome, or radiation therapy. However, she potentially was at risk for excessive UV light exposure. A detailed review of the literature is also provided. A moderately well differentiated sebaceous carcinoma was established histopathologically arising from the meibomian gland of the upper eyelid. In most areas, the cytoplasm contained small but distinct Oil-red-O positive vacuoles. Direct sequencing of p53 identified a G:C→A:T mutation at a dipyrimidine site. The mutation results in substitution of arginine for the highly conserved glycine at residue 199 located at the p53 dimer-dimer interface. Energy minimization structural modeling predicts that G199R will neutralize negative charges contributed by nearby inter- and intramonomeric glutamate residues. Discussion This study points to the importance of recognizing that sebaceous carcinoma can occur in young patients with no evidence for hereditary cancer risk or radiation therapy. The G199R substitution is anticipated to alter the stability of the p53 tetrameric complex. The role of UV light in the etiology of sebaceous carcinoma deserves further study. Our findings, taken together with those of others, suggest that different environmental factors could lead to the development of sebaceous carcinoma in different patients.

  17. Endothelial and trophoblast (dys)function in preeclampsia

    NARCIS (Netherlands)

    Donker, Rogier Bertrand

    2007-01-01

    As described in chapter 1, preeclampsia is a serious complication of pregnancy and worldwide one of the major causes of maternal and fetal morbidity and mortality. In severe, early-onset preeclampsia, i.e., placental preeclampsia, the syndrome originates from a hypoperfused and hypoxic placenta. One

  18. Very early-onset schizophrenia with secondary onset tic disorder

    OpenAIRE

    Shilpa A Telgote; Shreyas Shrikant Pendharkar; Amol D Kelkar; Sachin Bhojane

    2017-01-01

    Very early-onset schizophrenia (defined as an onset of psychosis before 13 years of age) is a rare and severe form of the disorder which is clinically and neurobiologically continuous with the adult-onset disorder. It is rarely reported

  19. Very Early-onset Schizophrenia with Secondary Onset Tic Disorder.

    Science.gov (United States)

    Telgote, Shilpa A; Pendharkar, Shreyas Shrikant; Kelkar, Amol D; Bhojane, Sachin

    2017-01-01

    Very early-onset schizophrenia (defined as an onset of psychosis before 13 years of age) is a rare and severe form of the disorder which is clinically and neurobiologically continuous with the adult-onset disorder. It is rarely reported tic disorder.

  20. Relationship of Heme Oxygenase-1 (HO-1 Level with Onset and Severity in Normotensive Pregnancy and Severe Preeclampsia

    Directory of Open Access Journals (Sweden)

    John Johannes Wantania

    2016-08-01

    Full Text Available Background: Preeclampsia still becomes a major problem in pregnancies. Various evidences showed that heme oxygenase-1 (HO-1 is very important in pregnancy. This study aims to understand the relationship of heme oxygenase-1 level with onset and severity in normotensive pregnancy and severe preeclampsia. Methods: This is a cross sectional analytic comparative study, the subjects consisted of 26 patients with normotensive pregnancies and 26 patients with severe preeclampsia. Blood samples from women with < 34 / ≥ 34 weeks’ normotensive pregnancies and women with severe preeclampsia were taken. HO-1 ELISA kit used to quantitate heme oxygenase-1 level in samples. Results: The level of heme oxygenase-1 in normotensive pregnant women < 34 weeks lower than severe preeclampsia pregnant women < 34 weeks (3.28 ± 0.46 ng/mL vs 4.20 ± 0.64 ng/mL, p=0.003, respectively. The median level of heme oxygenase-1 in normotensive pregnant women ≥ 34 weeks was 2.96 (2.41–4.39 ng/mL, while severe preeclampsia pregnant women ≥ 34 weeks was 3.52 (2.88–5.43 ng/mL, (p=0.040. The median level of heme oxygenase-1 in normotensive pregnant women was 3.04 (2.41–4.39 ng/mL, while severe preeclampsia pregnant women was 3.68 (2.88–5.67 ng/mL, (p=0.001. Conclusions: There is correlation between the incidence of severe preeclampsia with heme oxygenase-1 level in < 34 and ≥ 34 weeks of pregnancy. There is a significant difference between the level of heme oxygenase-1 in pregnant women with severe preeclampsia and in women with normotensive pregnancy. 

  1. Cerebellar ataxia of early onset

    International Nuclear Information System (INIS)

    Yamashita, Sumimasa; Miyake, Shota; Yamada, Michiko; Iwamoto, Hiroko; Yamada, Kazuhiko.

    1989-01-01

    Eight cases of childhood cerebellar ataxia were reported. All these cases showed chronic cerebellar ataxia with early onset, and the other diseases of cerebellum such as infections, neoplasms and storage diseases were excluded by clinical symptoms and laboratory findings including blood counts, blood chemistry, lactate, pyruvate, ceruloplasmine, urinalysis, serum immunoglobulins, amino acid analysis in blood and urine, CSF analysis, leukocyte lysosomal enzymes, MCV, EMG, EEG and brain X-CT. Two pairs of siblings were included in this study. The clinical diagnosis were cerebellar type (5), spinocerebellar type (1), one Marinesco-Sjoegren syndrome and undetermined type (1). The age of onset was 1 to 5 years. The chief complaint was motor developmental delay in 6 cases; among them 5 patients could walk alone at the ages of 2 to 3 years'. Mental retardation was observed in 7 cases and epilepsy in 2. TRH was effective in 5 cases. The MRI study revealed that the area of medial sagittal slice of the cerebellum was reduced significantly in all cases and also that of pons was reduced in 5 cases. Different from typical adult onset spinocerebellar degenerations, most of the present cases have achieved slow developmental milestones and the clinical course was not progressive. Genetic factors are suspected in the pathogenesis of this disease in some cases. (author)

  2. Serial assessment of cardiovascular control shows early signs of developing pre-eclampsia

    NARCIS (Netherlands)

    Rang, Sasika; Wolf, H.; van Montfrans, G. A.; Karemaker, J. M.

    2004-01-01

    Purpose To evaluate whether differences in autonomic cardiovascular control between normal pregnant women and women who develop pre-eclampsia later in pregnancy can be detected even before or early in pregnancy. Design We studied 42 women, 21 multigravid with a history of pre-eclampsia and 21

  3. Atrial Natriuretic Peptide (ANP) in early pregnancy is associated with development of preeclampsia in type 1 diabetes

    DEFF Research Database (Denmark)

    Nielsen, Lene Ringholm; Pedersen-Bjergaard, Ulrik; Thorsteinsson, Birger

    2011-01-01

    The vasoactive markers of cardiac overload Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP) are elevated in preeclampsia. This study documents higher ANP concentrations as early as at 9 weeks in type 1 diabetic women subsequently developing preeclampsia suggesting...... that preeclampsia is associated with cardiovascular changes in early pregnancy....

  4. Maternal endothelial damage as a disorder shared by early preeclampsia, late preeclampsia and intrauterine growth restriction.

    Science.gov (United States)

    Kwiatkowski, Sebastian; Dołegowska, Barbara; Kwiatkowska, Ewa; Rzepka, Rafał; Marczuk, Natalia; Loj, Beata; Torbè, Andrzej

    2017-10-26

    Preeclampsia (PE) and intrauterine growth restriction (IUGR) are separate disease entities that have frequently been reported as sharing the same pathogenesis. In both of them, angiogenesis disorders and generalized endothelial damage with an accompanying inflammation are the dominant symptoms. In this study, we attempted to prove that both these processes demonstrate the same profile in early PE, late PE and IUGR patients, while the only difference is in the degree of exacerbation of the lesions. In 167 patients divided into four groups, three of those with early PE, late PE and IUGR and one control group, fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), high sensitive c-reactive protein (hsCRP) and fibronectin were determined. The behavior of these parameters in each of the groups was studied, and correlations between them were sought for. Higher concentrations of sFlt-1, hsCRP and fibronectin and a lower concentration of PlGF were found in the study groups compared to the control group. Significant correlations were observed between the factors concerned. The higher values of disordered angiogenesis markers, endothelial damage markers and inflammatory markers both in the PE and the intrauterine growth restriction (IUGR) groups suggest the existence of shared disorders in the development of these pathologies. The correlations between disordered angiogenesis markers and endothelial damage markers argue in favor of a mutual relationship between these two processes in the development of pathologies evolving as secondary to placental ischemia. The results obtained confirm that the lesion profiles are the same in both PE and IUGR patients, which can be utilized in developing common diagnostic criteria.

  5. Atrial Natriuretic Peptide (ANP) in early pregnancy is associated with development of preeclampsia in type 1 diabetes

    DEFF Research Database (Denmark)

    Nielsen, Lene Ringholm; Pedersen-Bjergaard, Ulrik; Thorsteinsson, Birger

    2011-01-01

    The vasoactive markers of cardiac overload Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP) are elevated in preeclampsia. This study documents higher ANP concentrations as early as at 9 weeks in type 1 diabetic women subsequently developing preeclampsia suggesting that preecla......The vasoactive markers of cardiac overload Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP) are elevated in preeclampsia. This study documents higher ANP concentrations as early as at 9 weeks in type 1 diabetic women subsequently developing preeclampsia suggesting...... that preeclampsia is associated with cardiovascular changes in early pregnancy....

  6. Early- versus Late-Onset Dysthymia

    Science.gov (United States)

    Sansone, Lori A.

    2009-01-01

    In the current Diagnostic and Statistical Manual of Mental Disorders, dysthymic disorder is categorized as either early-onset or late-onset, based upon the emergence of symptoms before or after the age of 21, respectively. Does this diagnostic distinction have any meaningful clinical implications? In this edition of The Interface, we present empirical studies that have, within a single study, compared individuals with early-versus late-onset dysthymia. In this review, we found that, compared to those with late-onset dysthymia, early-onset patients are more likely to harbor psychiatric comorbidity both on Axis I and II, exhibit less psychological resilience, and have more prominent family loadings for mood disorders. These findings suggest that this distinction is meaningful and that the early-onset subtype of dysthymia is more difficult to effectively treat. PMID:20049145

  7. Early- versus Late-Onset Systemic Sclerosis

    Science.gov (United States)

    Alba, Marco A.; Velasco, César; Simeón, Carmen Pilar; Fonollosa, Vicent; Trapiella, Luis; Egurbide, María Victoria; Sáez, Luis; Castillo, María Jesús; Callejas, José Luis; Camps, María Teresa; Tolosa, Carles; Ríos, Juan José; Freire, Mayka; Vargas, José Antonio; Espinosa, Gerard

    2014-01-01

    Abstract Peak age at onset of systemic sclerosis (SSc) is between 20 and 50 years, although SSc is also described in both young and elderly patients. We conducted the present study to determine if age at disease onset modulates the clinical characteristics and outcome of SSc patients. The Spanish Scleroderma Study Group recruited 1037 patients with a mean follow-up of 5.2 ± 6.8 years. Based on the mean ± 1 standard deviation (SD) of age at disease onset (45 ± 15 yr) of the whole series, patients were classified into 3 groups: age ≤30 years (early onset), age between 31 and 59 years (standard onset), and age ≥60 years (late onset). We compared initial and cumulative manifestations, immunologic features, and death rates. The early-onset group included 195 patients; standard-onset group, 651; and late-onset, 191 patients. The early-onset group had a higher prevalence of esophageal involvement (72% in early-onset compared with 67% in standard-onset and 56% in late-onset; p = 0.004), and myositis (11%, 7.2%, and 2.9%, respectively; p = 0.009), but a lower prevalence of centromere antibodies (33%, 46%, and 47%, respectively; p = 0.007). In contrast, late-onset SSc was characterized by a lower prevalence of digital ulcers (54%, 41%, and 34%, respectively; p < 0.001) but higher rates of heart conduction system abnormalities (9%, 13%, and 21%, respectively; p = 0.004). Pulmonary hypertension was found in 25% of elderly patients and in 12% of the youngest patients (p = 0.010). After correction for the population effects of age and sex, standardized mortality ratio was shown to be higher in younger patients. The results of the present study confirm that age at disease onset is associated with differences in clinical presentation and outcome in SSc patients. PMID:24646463

  8. Early onset depression: the relevance of anxiety.

    Science.gov (United States)

    Parker, G; Wilhelm, K; Asghari, A

    1997-01-01

    The aim of this study was to determine risk factors that may differentiate early onset from late onset depression. A non-clinical cohort that had been assessed from 1978 to 1993 at 5 yearly intervals and that had a high prevalence rate of lifetime depression took part in the study. We established an appropriate age cut-off to distinguish early onset (i.e. before 26 years) of major and of minor depression, and examined the relevance of a number of possible determinants of early onset depression assessed over the life of the study. Despite several dimensional measures of depression, self-esteem and personality being considered, they generally failed (when assessed early in the study) to discriminate subsequent early onset depression, with the exception of low masculinity scores being a weak predictor of major and/or minor depression. Early onset depression was strongly predicted, however, by a lifetime episode of a major anxiety disorder, with generalised anxiety being a somewhat stronger and more consistent predictor than panic disorder, agoraphobia and minor anxiety disorders (ie social phobia, simple phobia). The possibility that anxiety may act as a key predispositional factor to early onset depression and to a greater number of depressive episodes is important in that clinical assessment and treatment of any existing anxiety disorder may be a more efficient and useful strategy than focussing primarily on the depressive disorder.

  9. Estrogen and early-onset Alzheimer's disease

    NARCIS (Netherlands)

    A.J.C. Slooter (Arjen); J.B. Bronzova (Juliana); A. Hofman (Albert); C. van Broeckhoven (Christine); C.M. van Duijn (Cornelia); J.C.M. Witteman (Jacqueline)

    1999-01-01

    textabstractEstrogen use may be protective for Alzheimer's disease with late onset. However, the effects on early onset Alzheimer's disease are unclear. This issue was studied in a population based setting. For each female patient, a female control was matched on age (within 5 years) and place of

  10. Genetics Home Reference: early-onset glaucoma

    Science.gov (United States)

    ... called a syndrome. If glaucoma appears before the age of 5 without other associated abnormalities, it is called primary congenital glaucoma. Other individuals experience early onset of primary open-angle glaucoma, the most ...

  11. Risk of early or severe pre-eclampsia related to pre-existing conditions

    DEFF Research Database (Denmark)

    Catov, Janet M; Ness, Roberta B; Kip, Kevin E

    2007-01-01

    BACKGROUND: Preeclampsia (PE), especially severe or early PE, is a leading cause of morbidity and mortality among mothers and infants. We estimated the population attributable fractions of severe or early PE associated with pre-existing conditions among nulliparous and multiparous women. METHODS...

  12. 3D power Doppler ultrasound in early diagnosis of preeclampsia.

    Science.gov (United States)

    Neto, R Moreira; Ramos, J G L

    2016-01-01

    Preeclampsia is a known cause of maternal, fetal and neonatal morbidity and mortality. Thus, evaluation of the predicting value of comparing 3D power Doppler indices (3DPD) of uteroplacental circulation (UPC) in the first and second trimester in patients who developed preeclampsia (PE) and those who did not and testing the hypothesis that the parameters of vascularization and placenta flow intensity, as determined by three-dimensional ultrasound (3D), are different in normal pregnancies compared with preeclampsia, could be a suitable screening method. A prospective observational study using 3D power Doppler were performed to evaluate the placental perfusion in 96 pregnant women who came to do the ultrasound routine between 11 and 14 weeks. The placental vascular index (VI), flow index (FI), blood vessels and blood flow index (VFI) by three-dimensional Doppler histogram were calculated. All patients repeated the exam between 16 and 20 weeks. The outcome was scored as normal or preeclamptic. Placental vascular indices including VI, FI and VFI were significantly lower in preeclamptic placentas compared with controls in the study performed in the second trimester (ppower Doppler assessment of placental vascular indices in the second trimester has the potential to detect women at risk for subsequent development of PE. Copyright © 2015 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

  13. Long-term impact of preeclampsia on maternal endometrial cancer risk

    DEFF Research Database (Denmark)

    Hallum, Sara; Pinborg, Anja; Kamper-Jørgensen, Mads

    2016-01-01

    BACKGROUND: Endometrial cancer is mainly dependent on oestrogen exposure. Preeclampsia has shown to reduce oestrogen levels hence preeclampsia may affect later endometrial cancer risk. METHODS: We conducted a case-control study of 523 Danish women with endometrial cancer and 52 299controls during...... 1978-2010. The association between preeclampsia and later endometrial cancer was evaluated overall and according to preeclampsia onset and type of endometrial cancer in conditional logistic regression models. RESULTS: We observed no overall association between preeclampsia and endometrial cancer risk...... (OR=1.11 (95% CI 0.68-1.81)). This was true for all endometrial cancer subtypes. In an analysis of preeclampsia onset, however, we report a markedly increased risk of endometrial cancer following early-onset preeclampsia (OR=2.64 (95% CI 1.29-5.38)). CONCLUSIONS: Although we report no obvious...

  14. Environmental noise pollution and risk of preeclampsia.

    Science.gov (United States)

    Auger, Nathalie; Duplaix, Mathilde; Bilodeau-Bertrand, Marianne; Lo, Ernest; Smargiassi, Audrey

    2018-08-01

    Environmental noise exposure is associated with a greater risk of hypertension, but the link with preeclampsia, a hypertensive disorder of pregnancy, is unclear. We sought to determine the relationship between environmental noise pollution and risk of preeclampsia during pregnancy. We analyzed a population-based cohort comprising 269,263 deliveries on the island of Montreal, Canada between 2000 and 2013. We obtained total environmental noise pollution measurements (LA eq24 , L den , L night ) from land use regression models, and assigned noise levels to each woman based on the residential postal code. We computed odds ratios (OR) and 95% confidence intervals (CI) for the association of noise with preeclampsia in mixed logistic regression models with participants as a random effect, and adjusted for air pollution, neighbourhood walkability, maternal age, parity, multiple pregnancy, comorbidity, socioeconomic deprivation, and year of delivery. We assessed whether noise exposure was more strongly associated with severe or early onset preeclampsia than mild or late onset preeclampsia. Prevalence of preeclampsia was higher for women exposed to elevated environmental noise pollution levels (LA eq24h  ≥ 65 dB(A) = 37.9 per 1000 vs. <50 dB(A) = 27.9 per 1000). Compared with 50 dB(A), an LA eq24h of 65.0 dB(A) was not significantly associated the risk of preeclampsia (OR 1.09, 95% CI 0.99-1.20). Associations were however present with severe (OR 1.29, 95% CI 1.09-1.54) and early onset (OR 1.71, 95% CI 1.20-2.43) preeclampsia, with results consistent across all noise indicators. The associations were much weaker or absent for mild and late preeclampsia. Environmental noise pollution may be a novel risk factor for pregnancy-related hypertension, particularly more severe variants of preeclampsia. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Prediction of preeclampsia in type 1 diabetes in early pregnancy by clinical predictors

    DEFF Research Database (Denmark)

    Vestgaard, Marianne; Sommer, Miriam Colstrup; Ringholm, Lene

    2018-01-01

    PURPOSE: The purpose of this study is to evaluate the prevalence and possible clinical predictors of preeclampsia present in early pregnancy among women with type 1 diabetes. METHODS: A systematic search of PubMed was conducted in April 2017. Inclusion criteria were largely unselected cohort, inc...

  16. A Common Profile of Disordered Angiogenic Factor Production and the Exacerbation of Inflammation in Early Preeclampsia, Late Preeclampsia, and Intrauterine Growth Restriction.

    Science.gov (United States)

    Kwiatkowski, Sebastian; Dołęgowska, Barbara; Kwiatkowska, Ewa; Rzepka, Rafał; Torbè, Andrzej; Bednarek-Jędrzejek, Magdalena

    2016-01-01

    Preeclampsia and intrauterine growth restriction are two separate disease entities that, according to numerous reports, share the same pathogenesis. In both, angiogenesis disorders and generalized inflammation are the dominant symptoms. In this study, we hypothesized that both diseases demonstrate the same profile in early preeclampsia, late preeclampsia, and intrauterine growth restriction patients, with the only difference being the degree of exacerbation of lesions. One hundred sixty-seven patients were enrolled in the study and divided into four groups: early preeclampsia, late preeclampsia, and intrauterine growth restriction groups, and one control group. Concentrations of the angiogenesis and inflammatory markers soluble fms-like tyrosine kinase receptor 1, placental growth factor, high-sensitivity C-reactive protein, and interleukin-6 were determined, and the behavior of these markers and correlations among them were studied. Higher concentrations of soluble fms-like tyrosine kinase receptor 1, high-sensitivity C-reactive protein, and interleukin-6 and a lower concentration of placental growth factor were observed in the study groups compared with the control group. No differences in concentrations of the studied markers were found among the study groups but significant correlations were observed. The higher values for the angiogenesis and inflammatory markers both in preeclampsia patients and patients with intrauterine growth restriction of placental origin compared with the control group suggest the existence of the same underlying disorders in the development of these pathologies. The observed mutual correlations for disordered angiogenesis and inflammatory markers are suggestive of a mutual relationship between these processes in the development of pathologies evolving secondary to placental ischemia. The same lesion profile was observed for both preeclampsia and 'placental' intrauterine growth restriction patients, which could be used in developing

  17. Associations between phenotypes of preeclampsia and thrombophilia.

    Science.gov (United States)

    Berks, Durk; Duvekot, Johannes J; Basalan, Hillal; De Maat, Moniek P M; Steegers, Eric A P; Visser, Willy

    2015-11-01

    Preeclampsia complicates 2-8% of all pregnancies. Studies on the association of preeclampsia with thrombophilia are conflicting. Clinical heterogeneity of the disease may be one of the explanations. The present study addresses the question whether different phenotypes of preeclampsia are associated with thrombophilia factors. Study design We planned a retrospective cohort study. From 1985 until 2010 women with preeclampsia were offered postpartum screening for the following thrombophilia factors: anti-phospholipid antibodies, APC-resistance, protein C deficiency and protein S deficiency, hyperhomocysteineamia, factor V Leiden and Prothrombin gene mutation. Hospital records were used to obtain information on phenotypes of the preeclampsia and placental histology. We identified 844 women with singleton pregnancies who were screened for thrombophilia factors. HELLP complicated 49% of pregnancies; Fetal growth restriction complicated 61% of pregnancies. Early delivery (preeclampsia was associated with protein S deficiency (p=0.01). Fetal growth restriction was associated with anti-phospholipid antibodies (ppreeclampsia was associated with anti-phospholipid antibodies (p=0.01). Extensive placental infarction (>10%) was associated with anti-phospholipid antibodies (ppreeclampsia, especially if complicated by fetal growth restriction, are associated with anti-phospholipid antibodies. Other phenotypes of preeclampsia, especially HELLP syndrome, were not associated with thrombophilia. We advise only to test for anti-phospholipid antibodies after early onset preeclampsia, especially if complicated by fetal growth restriction. We suggest enough evidence is presented to justify no further studies are needed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. First trimester pregnancy-associated plasma protein A and human chorionic gonadotropin-beta in early and late pre-eclampsia

    DEFF Research Database (Denmark)

    Karahasanovic, Azra; Sørensen, Steen; Nilas, Lisbeth

    2014-01-01

    Abstract Background: The aim of this study was to compare pregnancy-associated plasma protein A (PAPP-A) and the β-subunit of human chorionic gonadotropin (hCGβ) measured in maternal plasma at the first trimester screening, in women who later developed early or late pre-eclampsia (PE) to women...... with normal pregnancies. Methods: In the study were included 161 cases with PE and 88 controls with uncomplicated pregnancies. Plasma PAPP-A and hCGβ were measured between gestational age (GA) 8+2 and 14+0, and cases with early and late onset PE were compared with controls. Results: Median of hCGβ (Mo...

  19. Relationship between maternal immunological response during pregnancy and onset of preeclampsia.

    Science.gov (United States)

    Martínez-Varea, Alicia; Pellicer, Begoña; Perales-Marín, Alfredo; Pellicer, Antonio

    2014-01-01

    Maternofetal immune tolerance is essential to maintain pregnancy. The maternal immunological tolerance to the semiallogeneic fetus becomes greater in egg donation pregnancies with unrelated donors as the complete fetal genome is allogeneic to the mother. Instead of being rejected, the allogeneic fetus is tolerated by the pregnant woman in egg donation pregnancies. It has been reported that maternal morbidity during egg donation pregnancies is higher as compared with spontaneous or in vitro fertilization pregnancies. Particularly, egg donation pregnancies are associated with a higher incidence of pregnancy-induced hypertension and placental pathology. Preeclampsia, a pregnancy-specific disease characterized by the development of both hypertension and proteinuria, remains the leading cause of maternal and perinatal mortality and morbidity. The aim of this review is to characterize and relate the maternofetal immunological tolerance phenomenon during pregnancies with a semiallogenic fetus, which are the spontaneously conceived pregnancies and in vitro fertilization pregnancies, and those with an allogeneic fetus or egg donation pregnancies. Maternofetal immune tolerance in uncomplicated pregnancies and pathological pregnancies, such as those with preeclampsia, has also been assessed. Moreover, whether an inadequate maternal immunological response to the allogenic fetus could lead to a higher prevalence of preeclampsia in egg donation pregnancies has been addressed.

  20. Early pregnancy clinical risk factors for preeclampsia in women with type 1 and type 2 diabete

    DEFF Research Database (Denmark)

    Nørgaard, Sidse Kjærhus; Vestergaard, Marianne; Ásbjörnsdóttir, Björg

    Aim: To assess the prevalence of pregnancy-induced hypertensive disorders and to identify early clinical, modifiable predictors of preeclampsia in women with type 1 and type 2 diabetes. Methods: A population-based cohort study of 494 women with pre-existing diabetes (307 type 1 and 187 type 2...... diabetes), included at their first antenatal visit at 11±6 gestational weeks (mean±SD) from 2012 to 2016. Predictors of preeclampsia present at first antenatal visit were sought identified. Results: At the first antenatal visit HbA1c was 6.9±2.3 % (51±10 mmol/mol) vs. 6.8±2.6 % (49±14 mmol/mol) and blood...... pressure 120±12/76±8 mmHg vs. 122±14/79±10 mmHg, (p=0.16/p=0.001) in women with type 1 and type 2 diabetes, respectively. Preeclampsia developed in 40 women at 36±3 gestational weeks with delivery 8±9 days later. The prevalence of preeclampsia was 8% (9% vs. 7%) and gestational hypertension 8% (9% vs. 6...

  1. Genomes of early onset prostate cancer

    DEFF Research Database (Denmark)

    Weischenfeldt, Joachim; Korbel, Jan O.

    2017-01-01

    Purpose of review Prostate cancer is a disease of the elderly but a clinically relevant subset occurs early in life. In the current review, we discuss recent findings and the current understanding of the molecular underpinnings associated with early-onset prostate cancer (PCa) and the evidence...... supporting age-specific differences in the cancer genomes. Recent findings Recent surveys of PCa patient cohorts have provided novel age-dependent links between germline and somatic aberrations which points to differences in the molecular cause and treatment options. Summary Identifying the earliest...... receptor pathway....

  2. Baseline placental growth factor levels for the prediction of benefit from early aspirin prophylaxis for preeclampsia prevention.

    Science.gov (United States)

    Moore, Gaea S; Allshouse, Amanda A; Winn, Virginia D; Galan, Henry L; Heyborne, Kent D

    2015-10-01

    Placental growth factor (PlGF) levels early in pregnancy are lower in women who ultimately develop preeclampsia. Early initiation of low-dose aspirin reduces preeclampsia risk in some high risk women. We hypothesized that low PlGF levels may identify women at increased risk for preeclampsia who would benefit from aspirin. Secondary analysis of the MFMU High-Risk Aspirin study including singleton pregnancies randomized to aspirin 60mg/d (n=102) or placebo (n=72), with PlGF collected at 13w 0d-16w 6d. Within the placebo group, we estimated the probability of preeclampsia by PlGF level using logistic regression analysis, then determined a potential PlGF threshold for preeclampsia prediction using ROC analysis. We performed logistic regression modeling for potential confounders. ROC analysis indicated 87.71pg/ml as the threshold between high and low PlGF for preeclampsia-prediction. Within the placebo group high PlGF weakly predicted preeclampsia (AUC 0.653, sensitivity/specificity 63%/66%). We noted a 2.6-fold reduction in preeclampsia with aspirin in the high-PlGF group (12.15% aspirin vs 32.14% placebo, p=0.057), but no significant differences in preeclampsia in the low PlGF group (21.74% vs 15.91%, p=0.445). Unlike other studies, we found that high rather than low PlGF levels were associated with an increased preeclampsia risk. Low PlGF neither identified women at increased risk of preeclampsia nor women who benefitted from aspirin. Further research is needed to determine whether aspirin is beneficial in women with high PlGF, and whether the paradigm linking low PlGF and preeclampsia needs to be reevaluated. High-risk women with low baseline PlGF, a risk factor for preeclampsia, did not benefit from early initiation of low-dose aspirin. Copyright © 2015 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

  3. PP172. Indian scenario of preeclampsia and its consequences and early prophylaxis.

    Science.gov (United States)

    Jariwala, M C

    2012-07-01

    Preeclampsia remains one of the major obstetrical problems in less-developed countries. The causes of this condition are still unknown, we have designed a prevention protocol with new concept to describe the etiology and cause of preeclampsia. To study the effectiveness of the Jariwala's therapy and etiological causes of preeclapsia. we want to establish the new version of efficient prophylactic management to prevent the concequences of preeclampsia. We have selected 800 cases who have developed preeclampsia during any phase of pregnancy and tried to prevent the developing preeclampsia (predicted with roll over test, color doppler and weight gain and or edema) by Jariwala's protocol. our aim is to reduce the severity of disease process by early prediction and treatment. we have not included the cases who may have completely treated after the inclusion criteria to predict the preclampsia and treated. the inclusion criteris is strictly followed by a protocol designed. Jariwala's therapy is effective in mild to moderate cases of preeclampsia. Till date we have successfully treated 800 cases of mild to moderate preeclapsia with 98% neonates delivered with birth weight of 2kg and more, 92% neonates sent directly to home without any complication; and developed well at home. If we try to treat the blood pressure (during pregnancy) by anti hypertensive we have noticedà IUGR and rebound increase of blood pressure, means decrease maternal blood pressure à decrease placental supplyà deficient nutrientà rebound increase in toxin secretion (by fetus and placenta) à increase in blood pressure to supply more nutrient). So that it is my suggestion that the antihypertensive should be avoided if possible 2: increase permeability of placental membranes due to toxins secreted by fetus to supply more nutrient leads to increase permeability of placental membranes means increase protein loss from kidneys (due to toxins secreted from the fetus and placenta) increase third space

  4. Factor analysis of symptom profile in early onset and late onset OCD.

    Science.gov (United States)

    Grover, Sandeep; Sarkar, Siddharth; Gupta, Gourav; Kate, Natasha; Ghosh, Abhishek; Chakrabarti, Subho; Avasthi, Ajit

    2018-04-01

    This study aimed to assess the factor structure of early and late onset OCD. Additionally, cluster analysis was conducted in the same sample to assess the applicability of the factors. 345 participants were assessed with Yale Brown Obsessive Compulsive Scale symptom checklist. Patients were classified as early onset (onset of symptoms at age ≤ 18 years) and late onset (onset at age > 18 years) OCD depending upon the age of onset of the symptoms. Factor analysis and cluster analysis of early-onset and late-onset OCD was conducted. The study sample comprised of 91 early onset and 245 late onset OCD subjects. Males were more common in the early onset group. Differences in the frequency of phenomenology related to contamination related, checking, repeating, counting and ordering/arranging compulsions were present across the early and late onset groups. Factor analysis of YBOCS revealed a 3 factor solution for both the groups, which largely concurred with each other. These factors were named as hoarding and symmetry (factor-1), contamination (factor-2) and aggressive, sexual and religious factor (factor-3). To conclude this study shows that factor structure of symptoms of OCD seems to be similar between early-onset and late-onset OCD. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Genetics of Early-Onset Alzheimer Dementia

    Directory of Open Access Journals (Sweden)

    Rosa Rademakers

    2003-01-01

    Full Text Available Alzheimer�s dementia (AD is the most common degenerative disorder of the central nervous system. Although the onset of dementia is above 65 years of age in the majority of the patients (late-onset AD, LOAD, a small subgroup of patients develops AD before 65 years of age (early-onset AD, EOAD. To date 3 genes responsible for EOAD have been identified: the amyloid precursor protein gene (APP, presenilin 1 (PSEN1 and presenilin 2 (PSEN2. PSEN1 is the most frequently mutated EOAD gene with a mutation frequency of 18 to 50% in autosomal dominant EOAD. In addition, the e4 allele of the gene encoding apolipoprotein E (APOE was identified as a risk factor for both LOAD and EOAD. Many studies reported other susceptibility genes, but the APOE?4 alelle has been the only risk factor that was consistently replicated in all AD populations. Extensive cell biology research in the past ten years led to the hypothesis that the 4 EOAD genes lead to AD through a common biological pathway resulting in abnormal APP processing by subtle different mechanisms. Now, transgenic mice are produced to study the influence of EOAD mutations in vivo, eventually leading to the development of novel therapeutic strategies.

  6. Early changes of placenta-derived messenger RNA in maternal plasma – potential value for preeclampsia prediction?

    Directory of Open Access Journals (Sweden)

    Surugiu Sebastian

    2015-12-01

    Full Text Available Objective: the pourpose of the study was to determine if there are any differences between placenta derived plasmatic levels of messenger RNA in normal and future preeclamptic pregnancies and if these placental transcripts can predict preeclampsia long before clinical onset

  7. Strong family history and early onset of schizophrenia: about 2 ...

    African Journals Online (AJOL)

    Schizophrenia is a highly heritable psychotic disorder and high genetic loading is associated with early onset of the disease. The outcome of schizophrenia has also been linked with the age of onset as well as the presence of family history of the disease. Therefore families with patients with early onset Schizophrenia are ...

  8. Early-onset Alzheimer's Disease Phenotypes: Neuropsychology and Neural Networks

    Science.gov (United States)

    2017-05-11

    Alzheimer Disease, Early Onset; Alzheimer Disease; Alzheimer Disease, Late Onset; Dementia, Alzheimer Type; Logopenic Progressive Aphasia; Primary Progressive Aphasia; Visuospatial/Perceptual Abilities; Posterior Cortical Atrophy; Executive Dysfunction; Corticobasal Degeneration; Ideomotor Apraxia

  9. Cluster analysis to estimate the risk of preeclampsia in the high-risk Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) study

    Science.gov (United States)

    Marttinen, Pekka; Gillberg, Jussi; Lokki, A. Inkeri; Majander, Kerttu; Ordén, Maija-Riitta; Taipale, Pekka; Pesonen, Anukatriina; Räikkönen, Katri; Hämäläinen, Esa; Kajantie, Eero; Laivuori, Hannele

    2017-01-01

    Objectives Preeclampsia is divided into early-onset (delivery before 34 weeks of gestation) and late-onset (delivery at or after 34 weeks) subtypes, which may rise from different etiopathogenic backgrounds. Early-onset disease is associated with placental dysfunction. Late-onset disease develops predominantly due to metabolic disturbances, obesity, diabetes, lipid dysfunction, and inflammation, which affect endothelial function. Our aim was to use cluster analysis to investigate clinical factors predicting the onset and severity of preeclampsia in a cohort of women with known clinical risk factors. Methods We recruited 903 pregnant women with risk factors for preeclampsia at gestational weeks 12+0–13+6. Each individual outcome diagnosis was independently verified from medical records. We applied a Bayesian clustering algorithm to classify the study participants to clusters based on their particular risk factor combination. For each cluster, we computed the risk ratio of each disease outcome, relative to the risk in the general population. Results The risk of preeclampsia increased exponentially with respect to the number of risk factors. Our analysis revealed 25 number of clusters. Preeclampsia in a previous pregnancy (n = 138) increased the risk of preeclampsia 8.1 fold (95% confidence interval (CI) 5.7–11.2) compared to a general population of pregnant women. Having a small for gestational age infant (n = 57) in a previous pregnancy increased the risk of early-onset preeclampsia 17.5 fold (95%CI 2.1–60.5). Cluster of those two risk factors together (n = 21) increased the risk of severe preeclampsia to 23.8-fold (95%CI 5.1–60.6), intermediate onset (delivery between 34+0–36+6 weeks of gestation) to 25.1-fold (95%CI 3.1–79.9) and preterm preeclampsia (delivery before 37+0 weeks of gestation) to 16.4-fold (95%CI 2.0–52.4). Body mass index over 30 kg/m2 (n = 228) as a sole risk factor increased the risk of preeclampsia to 2.1-fold (95%CI 1.1–3

  10. Metabolomic biomarkers in serum and urine in women with preeclampsia.

    Directory of Open Access Journals (Sweden)

    Marie Austdal

    Full Text Available To explore the potential of magnetic resonance (MR metabolomics for study of preeclampsia, for improved phenotyping and elucidating potential clues to etiology and pathogenesis.Urine and serum samples from pregnant women with preeclampsia (n = 10, normal pregnancies (n = 10 and non-pregnant women (n = 10 matched by age and gestational age were analyzed with MR spectroscopy and subjected to multivariate analysis. Metabolites were then quantified and compared between groups.Urine and serum samples revealed clear differences between women with preeclampsia and both control groups (normal pregnant and non-pregnant women. Nine urine metabolites were significantly different between preeclampsia and the normal pregnant group. Urine samples from women with early onset preeclampsia clustered together in the multivariate analysis. The preeclampsia serum spectra showed higher levels of low and very-low density lipoproteins and lower levels of high-density lipoproteins when compared to both non-pregnant and normal pregnant women.The MR determined metabolic profiles in urine and serum from women with preeclampsia are clearly different from normal pregnant women. The observed differences represent a potential to examine mechanisms underlying different preeclampsia phenotypes in urine and serum samples in larger studies. In addition, similarities between preeclampsia and cardiovascular disease in metabolomics are demonstrated.

  11. Dynamic Cerebral Autoregulation in Pregnancy and the Risk of Preeclampsia

    DEFF Research Database (Denmark)

    Janzarik, Wibke G; Ehlers, Elena; Ehmann, Renata

    2014-01-01

    Preeclampsia may affect severely the cerebral circulation leading to impairment of cerebral autoregulation, edema, and ischemia. It is not known whether impaired autoregulation occurs before the clinical onset of preeclampsia, and whether this can predict the occurrence of preeclampsia. Seventy......) of respiratory-induced 0.1 Hz hemodynamic oscillations. Uterine artery ultrasound was performed to search for a notch sign as an early marker of general endothelial dysfunction. All women were followed up until 6 weeks after delivery for the occurrence of preeclampsia. The autoregulation parameter gain did...... not differ between pregnant and nonpregnant women. Phase was slightly but significantly higher in pregnant women, indicating better DCA. Women with a notch sign did not show altered DCA. A history of preeclampsia during a previous pregnancy was associated with lower phase in middle cerebral artery...

  12. Early biometric lag in the prediction of small for gestational age neonates and preeclampsia.

    Science.gov (United States)

    Schwartz, Nadav; Pessel, Cara; Coletta, Jaclyn; Krieger, Abba M; Timor-Tritsch, Ilan E

    2011-01-01

    An early fetal growth lag may be a marker of future complications. We sought to determine the utility of early biometric variables in predicting adverse pregnancy outcomes. In this retrospective cohort study, the crown-rump length at 11 to 14 weeks and the head circumference, biparietal diameter, abdominal circumference, femur length, humerus length, transverse cerebellar diameter, and estimated fetal weight at 18 to 24 weeks were converted to an estimated gestational age using published regression formulas. Sonographic fetal growth (difference between each biometric gestational age and the crown-rump length gestational age) minus expected fetal growth (number of days elapsed between the two scans) yielded the biometric growth lag. These lags were tested as predictors of small for gestational age (SGA) neonates (≤10th percentile) and preeclampsia. A total of 245 patients were included. Thirty-two (13.1%) delivered an SGA neonate, and 43 (17.6%) had the composite outcome. The head circumference, biparietal diameter, abdominal circumference, and estimated fetal weight lags were identified as significant predictors of SGA neonates after adjusted analyses (P biometric lag variables and the development of preeclampsia. Routinely available biometric data can be used to improve the prediction of adverse outcomes such as SGA. These biometric lags should be considered in efforts to develop screening algorithms for adverse outcomes.

  13. [Early onset scoliosis. What are the options?].

    Science.gov (United States)

    Farrington, D M; Tatay-Díaz, A

    2013-01-01

    The prognosis of children with progressive early onset scoliosis has improved considerably due to recent advances in surgical and non-surgical techniques and the understanding of the importance of preserving the thoracic space. Improvements in existing techniques and development of new methods have considerably improved the management of this condition. Derotational casting can be considered in children with documented progression of a <60° curve without previous surgical treatment. Both single and dual growing rods are effective, but the latter seem to offer better results. Hybrid constructs may be a better option in children who require a low-profile proximal anchor. The vertical expandable prosthetic titanium rib (VEPTR(®)) appears to be beneficial for patients with congenital scoliosis and fused ribs, and thoracic Insufficiency Syndrome. Children with medical comorbidities who may not tolerate repeated lengthenings should be considered for Shilla or Luque Trolley technique. Growth modulation using shape memory alloy staples or other tethers seem promising for mild curves, although more research is required to define their precise indications. Copyright © 2013 SECOT. Published by Elsevier Espana. All rights reserved.

  14. Early-onset stargardt disease: phenotypic and genotypic characteristics

    NARCIS (Netherlands)

    Lambertus, S.; Huet, R.A.C. van; Bax, N.M.; Hoefsloot, L.H.; Cremers, F.P.M.; Boon, C.J.F.; Klevering, B.J.; Hoyng, C.B.

    2015-01-01

    OBJECTIVE: To describe the phenotype and genotype of patients with early-onset Stargardt disease. DESIGN: Retrospective cohort study. PARTICIPANTS: Fifty-one Stargardt patients with age at onset onset, medical history, initial

  15. Evidence for a genetic etiology of early-onset delinquency.

    Science.gov (United States)

    Taylor, J; Iacono, W G; McGue, M

    2000-11-01

    Age at onset of antisocial behavior discriminates persistent and transitory offenders. The authors proposed that early-onset delinquency has an underlying genetic influence that manifests in problems related to inhibition, whereas late-onset delinquency is more environmentally mediated. To test these notions, they selected 36 early starters, 86 late starters, and 25 nondelinquent controls from a large sample of 11-year-old twins and compared them on several measures related to inhibition and a peer group measure. As expected, early starters had more psychological, behavioral, and emotional problems related to inhibition than late starters and controls. A longitudinal analysis indicated an increase an antisocial behavior among peers of late starters shortly before their delinquency onset. Family history data and a twin analysis provided evidence of greater genetic influence on early-onset than late-onset delinquency.

  16. Nearwork in early-onset myopia.

    Science.gov (United States)

    Saw, Seang-Mei; Chua, Wei-Han; Hong, Ching-Ye; Wu, Hui-Min; Chan, Wai-Ying; Chia, Kee-Seng; Stone, Richard A; Tan, Donald

    2002-02-01

    To determine the relationship of nearwork and myopia in young elementary school-age children in Singapore. A cross-sectional study of 1005 school children aged 7 to 9 years was conducted in two schools in Singapore. Cycloplegic autorefraction, keratometry, and biometry measurements were performed. In addition, the parents completed a detailed questionnaire on nearwork activity (books read per week, reading in hours per day and diopter hours [addition of three times reading, two times computer use, and two times video games use in hours per day]). Other risk factors, such as parental myopia, socioeconomic status, and light exposure history, were assessed. In addition to socioeconomic factors, several nearwork indices were associated with myopia in these young children. The multivariate adjusted odds ratio of higher myopia (at least -3.0 D) for children who read more than two books per week was 3.05 (95% confidence interval [CI], 1.80-5.18). However, the odds ratios of higher myopia for children who read more than 2 hours per day or with more than 8 diopter hours (1.50; 95% CI, 0.87-2.55 and 1.04; 95% CI, 0.61-1.78, respectively) were not significant, after controlling for several factors. Children aged 7 to 9 years with a greater current reading exposure were more likely to be myopic. This association of reading and myopia in a young age cohort was greater than the strength of the reading association generally found in older myopic subjects. Whether these results identify an association of early-onset myopia with nearwork activity or other potentially confounding factors is discussed.

  17. Does leisure time physical activity in early pregnancy protect against pre-eclampsia? Prospective cohort in Danish women

    DEFF Research Database (Denmark)

    Østerdal, M L; Strøm, M; Klemmensen, A K

    2008-01-01

    OBJECTIVE: To examine the association between physical activity in early pregnancy and risk of pre-eclampsia. DESIGN: Prospective cohort. SETTING: Denmark. POPULATION: A total of 85,139 pregnant Danish women, recruited between 1996 and 2002. METHODS: The authors assessed leisure time physical...

  18. Early- versus Late-Onset Dysthymia: A Meaningful Clinical Distinction?

    OpenAIRE

    Sansone, Randy A.; Sansone, Lori A.

    2009-01-01

    In the current Diagnostic and Statistical Manual of Mental Disorders, dysthymic disorder is categorized as either early-onset or late-onset, based upon the emergence of symptoms before or after the age of 21, respectively. Does this diagnostic distinction have any meaningful clinical implications? In this edition of The Interface, we present empirical studies that have, within a single study, compared individuals with early-versus late-onset dysthymia. In this review, we found that, compared ...

  19. Attention deficit hyperactivity disorder symptoms mediate early-onset smoking

    NARCIS (Netherlands)

    Huizink, A.C.; Van Lier, P.A.C.; Crijnen, A.A.M.

    2009-01-01

    Background/Aims: Symptoms of attention deficit hyperactivity disorder (ADHD) have often been associated with early-onset smoking. We hypothesize that reductions in ADHD symptoms due to an intervention have a mediating effect on early-onset smoking. Methods: In a universal, school-based, randomized

  20. Attention Deficit Hyperactivity Disorder Symptoms Mediate Early-Onset Smoking

    NARCIS (Netherlands)

    Huizink, A.C.; Lier, P.A.C. van; Crijnen, A.A.M.

    2009-01-01

    Background/Aims: Symptoms of attention deficit hyperactivity disorder (ADHD) have often been associated with early-onset smoking. We hypothesize that reductions in ADHD symptoms due to an intervention have a mediating effect on early-onset smoking. Methods: In a universal, school-based, randomized

  1. Attention deficit hyperactivity disorder symptoms mediate early-onset smoking

    NARCIS (Netherlands)

    A.C. Huizink (Anja); P.A.C. van Lier (Pol); A.A.M. Crijnen (Alfons)

    2008-01-01

    textabstractBackground/Aims: Symptoms of attention deficit hyperactivity disorder (ADHD) have often been associated with early-onset smoking. We hypothesize that reductions in ADHD symptoms due to an intervention have a mediating effect on early-onset smoking. Methods: In a universal, school-based,

  2. DNA Methylation as a Biomarker for Preeclampsia

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Cindy M.; Ralph, Jody L.; Wright, Michelle L.; Linggi, Bryan E.; Ohm, Joyce E.

    2014-10-01

    Background: Preeclampsia contributes significantly to pregnancy-associated morbidity and mortality as well as future risk of cardiovascular disease in mother and offspring, and preeclampsia in offspring. The lack of reliable methods for early detection limits the opportunities for prevention, diagnosis, and timely treatment. Purpose: The purpose of this study was to explore distinct DNA methylation patterns associated with preeclampsia in both maternal cells and fetal-derived tissue that represent potential biomarkers to predict future preeclampsia and inheritance in children. Method: A convenience sample of nulliparous women (N = 55) in the first trimester of pregnancy was recruited for this prospective study. Genome-wide DNA methylation was quantified in first-trimester maternal peripheral white blood cells and placental chorionic tissue from normotensive women and those with preeclampsia (n = 6/group). Results: Late-onset preeclampsia developed in 12.7% of women. Significant differences in DNA methylation were identified in 207 individual linked cytosine and guanine (CpG) sites in maternal white blood cells collected in the first trimester (132 sites with gain and 75 sites with loss of methylation), which were common to approximately 75% of the differentially methylated CpG sites identified in chorionic tissue of fetal origin. Conclusion: This study is the first to identify maternal epigenetic targets and common targets in fetal-derived tissue that represent putative biomarkers for early detection and heritable risk of preeclampsia. Findings may pave the way for diagnosis of preeclampsia prior to its clinical presentation and acute damaging effects, and the potential for prevention of the detrimental long-term sequelae.

  3. The common variant rs11646213 is associated with preeclampsia in Han Chinese women.

    Directory of Open Access Journals (Sweden)

    Ji-peng Wan

    Full Text Available BACKGROUND: Preeclampsia, characterized by hypertension and proteinuria, is a multifactorial disease caused by complex interactions between environmental and genetic factors. A recent genome-wide association study of blood pressure reported an association between hypertension and rs11646213. This study evaluated the association between preeclampsia and rs11646213. METHODS: A total of 454 cases and 460 controls were recruited to participate in this study. The single nucleotide polymorphism (SNP rs11646213 was genotyped by polymerase chain reaction (PCR and direct sequencing. RESULTS: The allele frequency of rs11646213 was significantly different between the preeclampsia and control groups (P = 0.017, OR = 1.36, 95% CI = 1.06-1.76. Differences were particularly significant in the severe preeclampsia subgroup (P = 0.002, OR = 1.54, 95% CI = 1.17-2.03 and the early-onset preeclampsia subgroup (P = 0.004, OR = 1.57, 95% CI = 1.16-2.13. Genotyping analysis showed that the T allele of rs11646213 could confer a risk for preeclampsia, severe preeclampsia and early-onset preeclampsia. CONCLUSIONS: Rs11646213 upstream of the CDH13 gene is associated with preeclampsia in Han Chinese women.

  4. Early- and Late-Onset Inherited Erythromelalgia

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2009-08-01

    Full Text Available A genotype-phenotype relationship at the clinical, cellular and molecular levels is shown in a case of erythromelalgia of relatively late onset, in a study at Yale University School of Medicine, and centers in China.

  5. Adverse Housing Conditions and Early-Onset Delinquency.

    Science.gov (United States)

    Jackson, Dylan B; Newsome, Jamie; Lynch, Kellie R

    2017-09-01

    Housing constitutes an important health resource for children. Research has revealed that, when housing conditions are unfavorable, they can interfere with child health, academic performance, and cognition. Little to no research, however, has considered whether adverse housing conditions and early-onset delinquency are significantly associated with one another. This study explores the associations between structural and non-structural housing conditions and delinquent involvement during childhood. Data from the Fragile Families and Child Wellbeing Study (FFCWS) were employed in this study. Each adverse housing condition was significantly associated with early-onset delinquency. Even so, disarray and deterioration were only significantly linked to early delinquent involvement in the presence of health/safety hazards. The predicted probability of early-onset delinquency among children exposed to housing risks in the presence of health/safety hazards was nearly three times as large as the predicted probability of early-onset delinquency among children exposed only to disarray and/or deterioration, and nearly four times as large as the predicted probability of early-onset delinquency among children exposed to none of the adverse housing conditions. The findings suggest that minimizing housing-related health/safety hazards among at-risk subsets of the population may help to alleviate other important public health concerns-particularly early-onset delinquency. Addressing household health/safety hazards may represent a fruitful avenue for public health programs aimed at the prevention of early-onset delinquency. © Society for Community Research and Action 2017.

  6. First trimester screening of circulating C19MC microRNAs and the evaluation of their potential to predict the onset of preeclampsia and IUGR.

    Directory of Open Access Journals (Sweden)

    Ilona Hromadnikova

    Full Text Available A nested case control study of a longitudinal cohort comparing pregnant women enrolled at 10 to 13 gestational weeks was carried out to evaluate risk assessment for preeclampsia and IUGR based on circulating placental specific C19MC microRNAs in early pregnancy.The expression of placental specific C19MC microRNAs (miR-516b-5p, miR-517-5p, miR-518b, miR-520a-5p, miR-520h, and miR-525-5p was determined in plasma samples from pregnancies that subsequently developed preeclampsia (n = 21, IUGR (n = 18, and 58 normal pregnancies using real-time PCR and comparative Ct method relative to synthetic Caenorhabditis elegans microRNA (cel-miR-39.Circulating C19MC microRNAs were up-regulated (miR-517-5p, p = 0.005; miR-518b, p = 0.013; miR-520h, p = 0.021 or showed a trend toward up-regulation in patients destined to develop preeclampsia (miR-520a-5p, p = 0.067; miR-525-5p, p = 0.073. MiR-517-5p had the best predictive performance for preeclampsia with a sensitivity of 42.9%, a specificity of 86.2%, a PPV of 52.9% and a NPV of 80.6%. The combination of all examined circulating C19MC microRNAs had no advantage over using only the miR-517-5p biomarker to predict the occurrence of preeclampsia (a sensitivity of 20.6%, a specificity of 90.8%, a PPV of 44.8%, and a NPV of 76.0%.Up-regulation of miR-517-5p, miR-518b and miR-520h was associated with a risk of later development of preeclampsia. First trimester screening of extracellular miR-517-5p identified a proportion of women with subsequent preeclampsia. No circulating C19MC microRNA biomarkers were identified that could predict later occurrence of IUGR.

  7. Early-onset Coronary Artery Disease: Clinical and Hereditary Aspects

    DEFF Research Database (Denmark)

    Christiansen, Morten Krogh

    2017-01-01

    ), and to characterize and quantify subclinical atherosclerosis in their relatives. Furthermore, the aim was to explore the impact of common genetic risk variants on the age of onset, familial clustering and disease severity. In study I, 143 patients with early-onset CAD were recruited from the Western Denmark Heart...

  8. Genetics of Severe Early Onset Epilepsies

    Science.gov (United States)

    2017-08-24

    Epilepsy; Epileptic Encephalopathy; Ohtahara Syndrome; Infantile Spasms; Dravet Syndrome; Malignant Migrating Partial Epilepsy of Infancy; Early Myoclonic Epileptic Encephalopathy; PCDH19-related Epilepsy and Related Conditions

  9. Genetics Home Reference: early-onset myopathy with fatal cardiomyopathy

    Science.gov (United States)

    ... in childhood, people with EOMFC may also develop joint deformities called contractures that restrict the movement of ... Home Edition for Patients and Caregivers: Dilated Cardiomyopathy Neuromuscular Disease Center, Washington University Orphanet: Early-onset myopathy ...

  10. Early Onset Malignancies - Genomic Study of Cancer Disparities

    Science.gov (United States)

    The Early Onset Malignancies Initiative studies the genomic basis of six cancers that develop at an earlier age, occur in higher rates, and are typically more aggressive in certain minority populations.

  11. Soluble Endoglin as a new marker for prediction of pre-eclampsia in early pregnancy

    Directory of Open Access Journals (Sweden)

    Khaled Gaber

    2010-01-01

    Conclusion: Pregnant women who are at risk of developing pre-eclampsia can be offered measuring these markers as a screening method to point out those who are more likely to develop pre-eclampsia and warrant close observation and intervention.

  12. Molecular Mechanisms of Preeclampsia.

    Science.gov (United States)

    Hod, Tammy; Cerdeira, Ana Sofia; Karumanchi, S Ananth

    2015-08-20

    Preeclampsia is a pregnancy-specific disease characterized by new onset hypertension and proteinuria after 20 wk of gestation. It is a leading cause of maternal and fetal morbidity and mortality worldwide. Exciting discoveries in the last decade have contributed to a better understanding of the molecular basis of this disease. Epidemiological, experimental, and therapeutic studies from several laboratories have provided compelling evidence that an antiangiogenic state owing to alterations in circulating angiogenic factors leads to preeclampsia. In this review, we highlight the role of key circulating antiangiogenic factors as pathogenic biomarkers and in the development of novel therapies for preeclampsia. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

  13. Molecular Mechanisms of Preeclampsia

    Science.gov (United States)

    Hod, Tammy; Cerdeira, Ana Sofia; Karumanchi, S. Ananth

    2015-01-01

    Preeclampsia is a pregnancy-specific disease characterized by new onset hypertension and proteinuria after 20 wk of gestation. It is a leading cause of maternal and fetal morbidity and mortality worldwide. Exciting discoveries in the last decade have contributed to a better understanding of the molecular basis of this disease. Epidemiological, experimental, and therapeutic studies from several laboratories have provided compelling evidence that an antiangiogenic state owing to alterations in circulating angiogenic factors leads to preeclampsia. In this review, we highlight the role of key circulating antiangiogenic factors as pathogenic biomarkers and in the development of novel therapies for preeclampsia. PMID:26292986

  14. Retinol-Binding Protein 4 and Lipids Prospectively Measured During Early to Mid-Pregnancy in Relation to Preeclampsia and Preterm Birth Risk.

    Science.gov (United States)

    Mendola, Pauline; Ghassabian, Akhgar; Mills, James L; Zhang, Cuilin; Tsai, Michael Y; Liu, Aiyi; Yeung, Edwina H

    2017-06-01

    Maternal retinol-binding protein 4 (RBP4) and lipids may relate to preeclampsia and preterm birth risk but longitudinal data are lacking. This study examines these biomarkers longitudinally during pregnancy in relation to preeclampsia and preterm birth risk. Maternal serum samples from the Calcium for Preeclampsia Prevention (CPEP) trial were analyzed at baseline: average 15 gestational weeks; mid-pregnancy: average 27 weeks; and at >34 weeks. We measured RBP4, total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides and lipoprotein (a) (Lp(a)). Cross-sectional logistic regression analyses estimated the odds ratio (OR) and 95% confidence intervals (CI) for preterm preeclampsia (n = 63), term preeclampsia (n = 104), and preterm delivery (n = 160) associated with RBP4 and lipids at baseline and mid-pregnancy compared with controls (n = 136). Longitudinal trajectories across pregnancy were assessed using mixed linear models with fixed effects. Adjusted models included clinical and demographic factors. RBP4 concentrations at baseline and mid-pregnancy were associated with a 4- to 8-fold increase in preterm preeclampsia risk but were not associated with term preeclampsia. RBP4 measured mid-pregnancy was also associated with preterm birth (OR = 6.67, 95% CI: 1.65, 26.84). Higher triglyceride concentrations in mid-pregnancy were associated with a 2- to 4-fold increased risk for both preeclampsia and preterm birth. Longitudinal models demonstrate that both preterm preeclampsia and preterm birth cases had elevated RBP4 throughout gestation. Elevated RBP4 is detectable early in pregnancy and its strong relation with preterm preeclampsia merits further investigation and confirmation to evaluate its potential use as a predictor, particularly among high-risk women. © Published by Oxford University Press on behalf of American Journal of Hypertension Ltd 2017. This work is written by (a) US Government employees(s) and is in the public domain in the US.

  15. Inflammatory Markers in the Second Trimester Prior to Clinical Onset of Preeclampsia, Intrauterine Growth Restriction, and Spontaneous Preterm Birth

    DEFF Research Database (Denmark)

    Haedersdal, Sofie; Salvig, Jannie Dalby; Aabye, Martine

    2013-01-01

    Low-grade inflammation has been associated with pregnancy complications including preeclampsia (PE), intrauterine growth restriction (IUGR), and spontaneous preterm birth (SPB). In an unmatched, nested case-control study, we assessed the possible predictive association of maternal C-reactive prot......Low-grade inflammation has been associated with pregnancy complications including preeclampsia (PE), intrauterine growth restriction (IUGR), and spontaneous preterm birth (SPB). In an unmatched, nested case-control study, we assessed the possible predictive association of maternal C...... to normotensive healthy pregnant controls (n = 127). We found no statistically significant difference in CRP, IP-10, or suPAR in second trimester plasma samples from pregnant women with later PE, IUGR, and SPB when compared to normotensive healthy controls. Second trimester plasma samples of CRP, IP-10, and su...

  16. Markers of neurodevelopmental impairments in early-onset psychosis

    Directory of Open Access Journals (Sweden)

    Petruzzelli MG

    2015-07-01

    Full Text Available Maria Giuseppina Petruzzelli,1 Lucia Margari,1 Francesco Craig,1 Maria Gloria Campa,1 Domenico Martinelli,2 Adriana Pastore,3 Marta Simone,1 Francesco Margari3 1Child and Adolescence Neuropsychiatry Unit, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University “Aldo Moro” of Bari, 2Department of Medical and Surgical Sciences; University of Foggia, Foggia, 3Psychiatry Unit, Department of Basic Medical Sciences, Neuroscience and Sense Organ, University “Aldo Moro” of Bari, Bari, Italy Background: The aim of this study was to assess the association between the clinical and neurobiological markers of neurodevelopmental impairments and early-onset schizophrenia spectrum psychosis. Methods: A sample of 36 patients with early-onset schizophrenia spectrum psychosis was compared to a control sample of 36 patients with migraine. We assessed early childhood neurodevelopmental milestones using a modified version of the General Developmental Scale, general intellectual ability using the Wechsler Intelligence Scale for Children–Revised or Leiter International Performance Scale–Revised for patients with speech and language abnormalities, and neurological soft signs with specific regard to subtle motor impairment. Results: Subjects with early-onset psychosis had a higher rate of impaired social development (P=0.001, learning difficulties (P=0.04, enuresis (P=0.0008, a lower intelligence quotient (P<0.001, and subtle motor impairments (P=0.005 than control subjects. Conclusion: We suggest that neurodevelopment in early-onset psychosis is characterized by a global impairment of functional and adaptive skills that manifests from early childhood, rather than a delay or limitation in language and motor development. The current evidence is based on a small sample and should be investigated in larger samples in future research. Keywords: early-onset psychosis, early-onset schizophrenia, neurodevelopment, social cognition

  17. [Use of sFlt-1/PlGF ratio in preeclampsia : a monocentric retrospective analysis].

    Science.gov (United States)

    Verbeurgt, L; Chantraine, F; De Marchin, J; Minon, J-M; Nisolle, M

    2017-09-01

    Soluble Fms-like tyrosine kinase 1 (sFlt-1) is an anti-angiogenic factor released in higher amounts in preeclampsia and implicated in endothelial dysfunction. sFlt-1/PlGF ratio is used in the prediction of preeclampsia. An sFlt-1/PlGF ratio inferior to 38 predicts the short-term absence of preeclampsia. A ratio ? 85 (early-onset PE) or ? 110 (late-onset of PE) could diagnose preeclampsia. In this study, sFlt-1/PlGF ratio has been measured in 183 patients. Sixty-seven preeclampsia have been diagnosed preeclamptic at delivery. The median sFlt-1/PlGF ratio was 100.3. The median ratio among women with preeclampsia (N=67) versus no preeclampsia (N=116) was 212.7 versus 35.4. In accordance with this analysis, an sFlt-1/PlGF ratio ? 38 has a sensibility of 95,5 % and a specificity of 73.3 %. The positive predictive value and the negative predictive value were 67.4 % and 96.6 %, respectively. These results suggest that sFlt-1/PlGF ratio is helpful in the diagnosis of preeclampsia.

  18. IFPA Senior Award Lecture: making sense of pre-eclampsia - two placental causes of preeclampsia?

    Science.gov (United States)

    Redman, C W; Sargent, I L; Staff, A C

    2014-02-01

    Incomplete spiral artery remodelling is the first of two stages of pre-eclampsia, typically of early onset. The second stage comprises dysregulated uteroplacental perfusion and placental oxidative stress. Oxidatively stressed syncytiotrophoblast (STB) over-secretes proteins that perturb maternal angiogenic balance and are considered to be pre-eclampsia biomarkers. We propose that, in addition and more fundamentally, these STB-derived proteins are biomarkers of a cellular (STB) stress response, which typically involves up-regulation of some proteins and down-regulation of others (positive and negative stress proteins respectively). Soluble vascular growth factor receptor-1 (sVEGFR-1) and reduced growth factor (PlGF) then exemplify positive and negative STB stress response proteins in the maternal circulation. Uncomplicated term pregnancy is associated with increasing sVEGFR-1 and decreasing PlGF, which can be interpreted as evidence of increasing STB stress. STB pathology, at or after term (for example focal STB necrosis) demonstrates this stress, with or without pre-eclampsia. We review the evidence that when placental growth reaches its limits at term, terminal villi become over-crowded with diminished intervillous pore size impeding intervillous perfusion with increasing intervillous hypoxia and STB stress. This type of STB stress has no antecedent pathology, so the fetuses are well-grown, as typifies late onset pre-eclampsia, and prediction is less effective than for the early onset syndrome because STB stress is a late event. In summary, abnormal placental perfusion and STB stress contribute to the pathogenesis of early and late onset pre-eclampsia. But the former has an extrinsic cause - poor placentation, whereas the latter has an intrinsic cause, 'microvillous overcrowding', as placental growth reaches its functional limits. This model explains important features of late pre-eclampsia and raises questions of how antecedent medical risk factors such as

  19. Early Pregnancy Biomarkers in Pre-Eclampsia: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Pensée Wu

    2015-09-01

    Full Text Available Pre-eclampsia (PE complicates 2%–8% of all pregnancies and is an important cause of perinatal morbidity and mortality worldwide. In order to reduce these complications and to develop possible treatment modalities, it is important to identify women at risk of developing PE. The use of biomarkers in early pregnancy would allow appropriate stratification into high and low risk pregnancies for the purpose of defining surveillance in pregnancy and to administer interventions. We used formal methods for a systematic review and meta-analyses to assess the accuracy of all biomarkers that have been evaluated so far during the first and early second trimester of pregnancy to predict PE. We found low predictive values using individual biomarkers which included a disintegrin and metalloprotease 12 (ADAM-12, inhibin-A, pregnancy associated plasma protein A (PAPP-A, placental growth factor (PlGF and placental protein 13 (PP-13. The pooled sensitivity of all single biomarkers was 0.40 (95% CI 0.39–0.41 at a false positive rate of 10%. The area under the Summary of Receiver Operating Characteristics Curve (SROC was 0.786 (SE 0.02. When a combination model was used, the predictive value improved to an area under the SROC of 0.893 (SE 0.03. In conclusion, although there are multiple potential biomarkers for PE their efficacy has been inconsistent and comparisons are difficult because of heterogeneity between different studies. Therefore, there is an urgent need for high quality, large-scale multicentre research in biomarkers for PE so that the best predictive marker(s can be identified in order to improve the management of women destined to develop PE.

  20. Early onset obsessive-compulsive disorder with and without tics.

    Science.gov (United States)

    de Mathis, Maria Alice; Diniz, Juliana B; Shavitt, Roseli G; Torres, Albina R; Ferrão, Ygor A; Fossaluza, Victor; Pereira, Carlos; Miguel, Eurípedes; do Rosario, Maria Conceicão

    2009-07-01

    Research suggests that obsessive-compulsive disorder (OCD) is not a unitary entity, but rather a highly heterogeneous condition, with complex and variable clinical manifestations. The aims of this study were to compare clinical and demographic characteristics of OCD patients with early and late age of onset of obsessive-compulsive symptoms (OCS); and to compare the same features in early onset OCD with and without tics. The independent impact of age at onset and presence of tics on comorbidity patterns was investigated. Three hundred and thirty consecutive outpatients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for OCD were evaluated: 160 patients belonged to the "early onset" group (EOG): before 11 years of age, 75 patients had an "intermediate onset" (IOG), and 95 patients were from the "late onset" group (LOG): after 18 years of age. From the 160 EOG, 60 had comorbidity with tic disorders. The diagnostic instruments used were: the Yale-Brown Obsessive Compulsive Scale and the Dimensional Yale-Brown Obsessive Compulsive Scale (DY-BOCS), Yale Global Tics Severity Scale, and Structured Clinical Interview for DSM-IV Axis I Disorders-patient edition. Statistical tests used were: Mann-Whitney, full Bayesian significance test, and logistic regression. The EOG had a predominance of males, higher frequency of family history of OCS, higher mean scores on the "aggression/violence" and "miscellaneous" dimensions, and higher mean global DY-BOCS scores. Patients with EOG without tic disorders presented higher mean global DY-BOCS scores and higher mean scores in the "contamination/cleaning" dimension. The current results disentangle some of the clinical overlap between early onset OCD with and without tics.

  1. Serum Leptin Measured in Early Pregnancy Is Higher in Women With Preeclampsia Compared With Normotensive Pregnant Women

    DEFF Research Database (Denmark)

    Taylor, Brandie; Ness, Roberta B; Olsen, Jørn

    2015-01-01

    Leptin, an adipocyte-derived hormone, plays an important role in reproduction and angiogenesis. Studies examining leptin in preeclampsia are inconsistent, possibly because of small sample sizes and variability in sampling and outcome. We conducted a nested case-control study to examine associations...... between serum leptin (measured: 9-26 weeks gestation) and preeclampsia among 430 primiparous preeclamptic women and 316 primiparous normotensive controls from the Danish National Birth Cohort. Median (interquartile range) leptin concentrations were calculated. Associations between leptin and preeclampsia...... (blood pressure ≥140/90 mm Hg), term preeclampsia (preeclampsia and delivery ≥37 weeks gestation), or preterm preeclampsia (preeclampsia and delivery

  2. Differences between early and late onset adult depression

    DEFF Research Database (Denmark)

    Drachmann Bukh, Jens; Bock, Camilla; Vinberg, Maj

    2011-01-01

    episode depression were systematically recruited. Characteristics including psychiatric co-morbidity, personality disorders and traits, stressful life events prior to onset, family history, and treatment outcome were assessed by structured interviews and compared by chi-square tests for categorical data...... prevalence of co-morbid personality disorders, higher levels of neuroticism, and a lower prevalence of stressful life events preceding onset compared to patients with later age-of-onset. There were no differences in severity of the depressive episode, treatment outcome or family loading of psychiatric......, t-tests for continuous parametric data and Mann-Whitney U-test for continuous nonparametric data. Logistic and multiple regression analyses were used to adjust the analyses for potentially confounding variables. Results: Patients with early onset of depression were characterised by a higher...

  3. Vascular dysfunction in women with a history of preeclampsia and intrauterine growth restriction: insights into future vascular risk.

    Science.gov (United States)

    Yinon, Yoav; Kingdom, John C P; Odutayo, Ayodele; Moineddin, Rahim; Drewlo, Sascha; Lai, Vesta; Cherney, David Z I; Hladunewich, Michelle A

    2010-11-02

    Women with a history of placental disease are at increased risk for the future development of vascular disease. It is unknown whether preexisting endothelial dysfunction underlies both the predisposition to placental disease and the later development of vascular disease. The aim of this study was to assess vascular function in postpartum women and to determine whether differences emerged depending on the presentation of placental disease. Women with a history of early-onset preeclampsia (n=15), late-onset preeclampsia (n=9), intrauterine growth restriction without preeclampsia (n=9), and prior normal pregnancy (n=16) were studied 6 to 24 months postpartum. Flow-mediated vasodilatation and flow-independent (glyceryl trinitrate-induced) vasodilatation were studied through the use of high-resolution vascular ultrasound examination of the brachial artery. Arterial stiffness was assessed by pulse-wave analysis (augmentation index). Laboratory assessment included circulating angiogenic factors (vascular endothelial growth factor, soluble fms-like tyrosine kinase 1, placental growth factor, and soluble endoglin). Flow-mediated vasodilatation was significantly reduced in women with previous early-onset preeclampsia and intrauterine growth restriction compared with women with previous late-onset preeclampsia and control subjects (3.2±2.7% and 2.1±1.2% versus 7.9±3.8% and 9.1±3.5%, respectively; Pwomen with previous early-onset preeclampsia and intrauterine growth restriction, but not among late preeclamptic women and control subjects (P=0.0105). Circulating angiogenic factors were similar in all groups. Only women with a history of early-onset preeclampsia or intrauterine growth restriction without preeclampsia exhibit impaired vascular function, which might explain their predisposition to placental disease and their higher risk of future vascular disease.

  4. Early Onset Marfan Syndrome: Atypical Clinical Presentation of Two Cases

    Directory of Open Access Journals (Sweden)

    Ozyurt Abdullah

    2015-06-01

    Full Text Available Early onset Marfan Syndrome (eoMFS is a rare, severe form of Marfan Syndrome (MFS. The disease has a poor prognosis and most patients present with resistance to heart failure treatment during the newborn period. This report presents two cases of eoMFS with similar clinical features diagnosed in the newborn period and who died at an early age due to the complications related to the involvement of the cardiovascular system.

  5. [Early-onset and late-onset male hypogonadotropic hypogonadism and osteoporosis].

    Science.gov (United States)

    Okada, Hiroshi; Shin, Takeshi; Kobori, Yoshitomo

    2016-07-01

    Hypogonadism is classified into two major clinical entities, namely early-onset hypogonadism and late-onset hypogonadism. The former is characterized by the malfunction of hypothalamo-pituitary-gonadal(testicular)axis or by the primary hypofunction of testes(e.g. Klinefelter's syndrome). The latter is summarized as LOH syndrome which is attributed to the dropped level of bioavailable testosterone. In these diseases testosterone is the key molecule which may cause various symptoms relating not only to physical health but also to mental or psychologic health. In this review issues concerning bone health in these disease are described.

  6. Neurocognition in Early-Onset Schizophrenia and Schizoaffective Disorders

    Science.gov (United States)

    Hooper, Stephen R.; Giuliano, Anthony J.; Youngstrom, Eric A.; Breiger, David; Sikich, Linmarie; Frazier, Jean A.; Findling, Robert L.; McClellan, Jon; Hamer, Robert M.; Vitiello, Benedetto; Lieberman, Jeffrey A.

    2010-01-01

    Objective: We examined the neuropsychological functioning of youth enrolled in the NIMH funded trial, Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS). We compared the baseline neuropsychological functioning of youth with schizophrenia (SZ, n = 79) to those with schizoaffective disorder (SA, n = 40), and examined the relationship…

  7. GRIN1 Mutations in Early-Onset Epileptic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Wenjuan Chen

    2015-06-01

    Full Text Available Investigators from Yokohama City University and other medical centers in Israel and Japan reported mutations on N-methyl-D-aspartate (NMDA receptors subunit GRIN1 (GluN1 identified in patients with nonsyndromic intellectual disability and early-onset epileptic encephalopathy.

  8. Early Onset Childhood Obesity and Risk of Metabolic Syndrome

    Centers for Disease Control (CDC) Podcasts

    This podcast features Lorena Pacheco, a doctoral student at the University of California San Diego and one of the winners of PCD's 2017 Student Research Paper Contest. Lorena answers questions about her winning research, which focuses on the relationship between early onset obesity as a risk factor for increased metabolic syndrome in Chilean children.

  9. Early Onset Bipolar Spectrum Disorder: Psychopharmacological, Psychological, and Educational Management

    Science.gov (United States)

    McIntosh, David E.; Trotter, Jeffrey S.

    2006-01-01

    Although published research continues to advocate medication as the first line of treatment for early onset bipolar spectrum disorder (EOBSD; N. Lofthouse & M.A. Fristad, 2004), preliminary research demonstrating the utility of cognitive, cognitive-behavioral, and psychoeducational therapies is promising. It appears as if future treatment of EOBSD…

  10. Neutrophil CD64 in early-onset neonatal sepsis

    African Journals Online (AJOL)

    EL-HAKIM

    of 3.5 to 8 cases per 1,000 live births; and mortality rate 16 to 30%. Cytokines, produced by ... 40 weeks with a picture of early onset neonatal sepsis within 48 hours of life admitted to neonatal ..... Infect Dis J 2000;19 (9):879-87. 5. Gonzalez BE ...

  11. Predictors of neonatal outcome in early-onset placental dysfunction

    NARCIS (Netherlands)

    Baschat, Ahmet A.; Cosmi, Erich; Bilardo, Catarina M.; Wolf, Hans; Berg, Christoph; Rigano, Serena; Germer, Ute; Moyano, Dolores; Turan, Sifa; Hartung, John; Bhide, Amarnath; Müller, Thomas; Bower, Sarah; Nicolaides, Kypros H.; Thilaganathan, Baskaran; Gembruch, Ulrich; Ferrazzi, Enrico; Hecher, Kurt; Galan, Henry L.; Harman, Chris R.

    2007-01-01

    To identify specific estimates and predictors of neonatal morbidity and mortality in early onset fetal growth restriction due to placental dysfunction. Prospective multicenter study of prenatally diagnosed growth-restricted liveborn neonates of less than 33 weeks of gestational age. Relationships

  12. Genome-Wide Mapping of 5mC and 5hmC Identified Differentially Modified Genomic Regions in Late-Onset Severe Preeclampsia: A Pilot Study.

    Directory of Open Access Journals (Sweden)

    Lisha Zhu

    Full Text Available Preeclampsia (PE is a leading cause of perinatal morbidity and mortality. However, as a common form of PE, the etiology of late-onset PE is elusive. We analyzed 5-methylcytosine (5mC and 5-hydroxymethylcytosine (5hmC levels in the placentas of late-onset severe PE patients (n = 4 and normal controls (n = 4 using a (hydroxymethylated DNA immunoprecipitation approach combined with deep sequencing ([h]MeDIP-seq, and the results were verified by (hMeDIP-qPCR. The most significant differentially methylated regions (DMRs were verified by MassARRAY EppiTYPER in an enlarged sample size (n = 20. Bioinformatics analysis identified 714 peaks of 5mC that were associated with 403 genes and 119 peaks of 5hmC that were associated with 61 genes, thus showing significant differences between the PE patients and the controls (>2-fold, p<0.05. Further, only one gene, PTPRN2, had both 5mC and 5hmC changes in patients. The ErbB signaling pathway was enriched in those 403 genes that had significantly different 5mC level between the groups. This genome-wide mapping of 5mC and 5hmC in late-onset severe PE and normal controls demonstrates that both 5mC and 5hmC play epigenetic roles in the regulation of the disease, but work independently. We reveal the genome-wide mapping of DNA methylation and DNA hydroxymethylation in late-onset PE placentas for the first time, and the identified ErbB signaling pathway and the gene PTPRN2 may be relevant to the epigenetic pathogenesis of late-onset PE.

  13. Early onset marijuana use is associated with learning inefficiencies.

    Science.gov (United States)

    Schuster, Randi Melissa; Hoeppner, Susanne S; Evins, A Eden; Gilman, Jodi M

    2016-05-01

    Verbal memory difficulties are the most widely reported and persistent cognitive deficit associated with early onset marijuana use. Yet, it is not known what memory stages are most impaired in those with early marijuana use. Forty-eight young adults, aged 18-25, who used marijuana at least once per week and 48 matched nonusing controls (CON) completed the California Verbal Learning Test, Second Edition (CVLT-II). Marijuana users were stratified by age of initial use: early onset users (EMJ), who started using marijuana at or before age 16 (n = 27), and late onset marijuana user group (LMJ), who started using marijuana after age 16 (n = 21). Outcome variables included trial immediate recall, total learning, clustering strategies (semantic clustering, serial clustering, ratio of semantic to serial clustering, and total number of strategies used), delayed recall, and percent retention. Learning improved with repetition, with no group effect on the learning slope. EMJ learned fewer words overall than LMJ or CON. There was no difference between LMJ and CON in total number of words learned. Reduced overall learning mediated the effect on reduced delayed recall among EMJ, but not CON or LMJ. Learning improved with greater use of semantic versus serial encoding, but this did not vary between groups. EMJ was not related to delayed recall after adjusting for encoding. Young adults reporting early onset marijuana use had learning weaknesses, which accounted for the association between early onset marijuana use and delayed recall. No amnestic effect of marijuana use was observed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  14. Atypical antipsychotics in the treatment of early-onset schizophrenia

    Directory of Open Access Journals (Sweden)

    Hrdlicka M

    2015-04-01

    Full Text Available Michal Hrdlicka, Iva Dudova Department of Child Psychiatry, Charles University Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic Abstract: Atypical antipsychotics (AAPs have been successfully used in early-onset schizophrenia (EOS. This review summarizes the randomized, double-blind, controlled studies of AAPs in EOS, including clozapine, risperidone, olanzapine, aripiprazole, paliperidone, quetiapine, and ziprasidone. No significant differences in efficacy between AAPs were found, with the exception of clozapine and ziprasidone. Clozapine demonstrated superior efficacy in treatment-resistant patients with EOS, whereas ziprasidone failed to demonstrate efficacy in the treatment of EOS. Our review also focuses on the onset of action and weight gain associated with AAPs. The data on onset of action of AAPs in pediatric psychiatry are scanty and inconsistent. Olanzapine appears to cause the most significant weight gain in patients with EOS, while ziprasidone and aripiprazole seem to cause the least. Keywords: early-onset schizophrenia, atypical antipsychotics, efficacy, onset of action, weight gain

  15. Does early-onset multiple sclerosis differ from adult-onset form in Iranian people

    Directory of Open Access Journals (Sweden)

    Fereshteh Ashtari

    2010-01-01

    Full Text Available Background: Few studies have attempted to delineate the clinical profile of multiple Sclerosis (MS among people of Asia. This study sought to identify the characteristics of early-onset Multiple Sclerosis (EOMS comparison to adult-onset form (AOMS in Isfahan, IRAN. Methods: This prospective study was conducted on 104 youths with multiple sclerosis beginning before the age of 16 years and 123 patients with adult-onset multiple sclerosis. Patients were observed for a mean period of 5 years. The common presenting symptoms, MRI finding, course of disease and disability score were compared between the two groups. Results: The mean onset age of disease in youths and adults were 14 ± 1.9 and 27.7 ± 8.06 years, respectively. Female/male ratio was 4.47:1 in EOMS and 3.92:1 in AOMS, this ratio was 7:1 in early childhood MS (≤ 10 year. The most common presenting symptom was optic neuritis in the EOMS group and paresthesia in AOMS. Optic neuritis was common in AOMS too, but brainstem/cerebellar signs were more common in EOMS than AOMS. Seizure occurred more frequently in EOMS than in the AOMS group (12.6% vs. 1.6%, respectively, p < 0.001. MRI showed that brainstem plaques were more prevalent in the EOMS compared with the AOMS group. Conclusions: It was concluded that early-onset MS does not significantly differ from adult form in terms of major clinical manifestation and course of disease, however Seizure is more common in EOMS, and brainstem and cerebellar symptoms as presenting symptom are more common.

  16. Intraspinal anomalies in early-onset idiopathic scoliosis.

    Science.gov (United States)

    Pereira, E A C; Oxenham, M; Lam, K S

    2017-06-01

    In the United Kingdom, lower incidences of intraspinal abnormalities in patients with early onset idiopathic scoliosis have been observed than in studies in other countries. We aimed to determine the rates of these abnormalities in United Kingdom patients diagnosed with idiopathic scoliosis before the age of 11 years. This retrospective study of patients attending an urban scoliosis clinic identified 71 patients satisfying a criteria of: clinical diagnosis of idiopathic scoliosis; age of onset ten years and 11 months or less; MRI screening for intraspinal abnormalities. United Kingdom census data combined with patient referral data was used to calculate incidence. Mean age at diagnosis was six years with 39 right-sided and 32 left-sided curves. Four patients (5.6%) were found to have intraspinal abnormalities on MRI. These consisted of: two combined Arnold-Chiari type 1 malformations with syrinx; one syrinx with a low lying conus; and one isolated syrinx. Overall annual incidence of early onset idiopathic scoliosis was one out of 182 000 (0.0006%). This study reports the lowest rates to date of intraspinal anomalies in patients with early onset idiopathic scoliosis, adding to knowledge regarding current incidences of these abnormalities as well as any geographical variation in the nature of the disease. Cite this article: Bone Joint J 2017;99-B:829-33. ©2017 The British Editorial Society of Bone & Joint Surgery.

  17. Combination of serum angiopoietin-2 and uterine artery Doppler for prediction of preeclampsia.

    Science.gov (United States)

    Puttapitakpong, Ploynin; Phupong, Vorapong

    2016-02-01

    The aim of this study was to determine the predictive value of the combination of serum angiopoietin-2 (Ang-2) levels and uterine artery Doppler for the detection of preeclampsia in women at 16-18 weeks of gestation and to identify other pregnancy complications that could be predicted with these combined tests. Maternal serum Ang-2 levels were measured, and uterine artery Doppler was performed in 400 pregnant women. The main outcome was preeclampsia. The predictive values of this combination were calculated. Twenty-five women (6.3%) developed preeclampsia. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of uterine artery Doppler combined with serum Ang-2 levels for the prediction of preeclampsia were 24.0%, 94.4%, 22.2% and 94.9%, respectively. For the prediction of early-onset preeclampsia, the sensitivity, specificity, PPV and NPV were 57.1%, 94.1%, 14.8% and 99.2%, respectively. Patients with abnormal uterine artery Doppler and abnormal serum Ang-2 levels (above 19.5 ng ml(-1)) were at higher risk for preterm delivery (relative risk=2.7, 95% confidence interval 1.2-5.8). Our findings revealed that the combination of uterine artery Doppler and serum Ang-2 levels at 16-18 weeks of gestation can be used to predict early-onset preeclampsia but not overall preeclampsia. Thus, this combination may be a useful early second trimester screening test for the prediction of early-onset preeclampsia.

  18. Early and phasic cortical metabolic changes in vestibular neuritis onset.

    Directory of Open Access Journals (Sweden)

    Marco Alessandrini

    Full Text Available Functional brain activation studies described the presence of separate cortical areas responsible for central processing of peripheral vestibular information and reported their activation and interactions with other sensory modalities and the changes of this network associated to strategic peripheral or central vestibular lesions. It is already known that cortical changes induced by acute unilateral vestibular failure (UVF are various and undergo variations over time, revealing different cortical involved areas at the onset and recovery from symptoms. The present study aimed at reporting the earliest change in cortical metabolic activity during a paradigmatic form of UVF such as vestibular neuritis (VN, that is, a purely peripheral lesion of the vestibular system, that offers the opportunity to study the cortical response to altered vestibular processing. This research reports [(18F]fluorodeoxyglucose positron emission tomography brain scan data concerning the early cortical metabolic activity associated to symptoms onset in a group of eight patients suffering from VN. VN patients' cortical metabolic activity during the first two days from symptoms onset was compared to that recorded one month later and to a control healthy group. Beside the known cortical response in the sensorimotor network associated to vestibular deafferentation, we show for the first time the involvement of Entorhinal (BAs 28, 34 and Temporal (BA 38 cortices in early phases of symptomatology onset. We interpret these findings as the cortical counterparts of the attempt to reorient oneself in space counteracting the vertigo symptom (Bas 28, 34 and of the emotional response to the new pathologic condition (BA 38 respectively. These interpretations were further supported by changes in patients' subjective ratings in balance, anxiety, and depersonalization/derealization scores when tested at illness onset and one month later. The present findings contribute in expanding

  19. Early-onset childhood sarcoidosis: a case report

    Directory of Open Access Journals (Sweden)

    Lai-San Wong

    2011-12-01

    Full Text Available Sarcoidosis is a multisystemic granulomatous disease of unknown etiology and it most commonly affects young adults. Childhood sarcoidosis is relatively rare; older children usually present a picture similar to that of adults, with frequent hilar lymphadenopathy and pulmonary infiltration. Early-onset (<4 years of age childhood sarcoidosis is a unique disease and has a different presentation. It is characterized by arthritis, uveitis, and cutaneous involvement. The prognosis of early-onset childhood sarcoidosis varies in different studies due to the rarity of the disease. The treatment of choice in systemic involvement of childhood sarcoidosis is corticosteroids. Methotrexate can also be considered in the long-term treatment due to its safety, effectiveness, and steroid-sparing effect in children.

  20. Genetic Determinism of Primary Early-Onset Osteoarthritis.

    Science.gov (United States)

    Aury-Landas, Juliette; Marcelli, Christian; Leclercq, Sylvain; Boumédiene, Karim; Baugé, Catherine

    2016-01-01

    Osteoarthritis (OA) is the most common joint disease worldwide. A minority of cases correspond to familial presentation characterized by early-onset forms which are genetically heterogeneous. This review brings a new point of view on the molecular basis of OA by focusing on gene mutations causing early-onset OA (EO-OA). Recently, thanks to whole-exome sequencing, a gain-of-function mutation in the TNFRSF11B gene was identified in two distant family members with EO-OA, opening new therapeutic perspectives for OA. Indeed, unraveling the molecular basis of rare Mendelian OA forms will improve our understanding of molecular processes involved in OA pathogenesis and will contribute to better patient diagnosis, management, and therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Age at onset of DSM-IV pathological gambling in a non-treatment sample: Early- versus later-onset.

    Science.gov (United States)

    Black, Donald W; Shaw, Martha; Coryell, William; Crowe, Raymond; McCormick, Brett; Allen, Jeff

    2015-07-01

    Pathological gambling (PG) is a prevalent and impairing public health problem. In this study we assessed age at onset in men and women with PG and compared the demographic and clinical picture of early- vs. later-onset individuals. We also compared age at onset in PG subjects and their first-degree relatives with PG. Subjects with DSM-IV PG were recruited during the conduct of two non-treatment clinical studies. Subjects were evaluated with structured interviews and validated questionnaires. Early-onset was defined as PG starting prior to age 33years. Age at onset of PG in the 255 subjects ranged from 8 to 80years with a mean (SD) of 34.0 (15.3) years. Men had an earlier onset than women. 84% of all subjects with PG had developed the disorder by age 50years. Early-onset subjects were more likely to be male, to prefer action games, and to have substance use disorders, antisocial personality disorder, attention deficit/hyperactivity disorder, trait impulsiveness, and social anxiety disorder. Later-onset was more common in women and was associated with a preference for slots and a history of sexual abuse. Age at onset of PG is bimodal and differs for men and women. Early-onset PG and later-onset PG have important demographic and clinical differences. The implications of the findings are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Maternal serum bisphenol A levels and risk of pre-eclampsia: a nested case–control study

    Science.gov (United States)

    Ye, Yunzhen; Zhou, Qiongjie; Feng, Liping; Wu, Jiangnan; Xiong, Yu; Li, Xiaotian

    2017-01-01

    Abstract Background Although recent studies have indicated the potential adverse effects of maternal bisphenol A (BPA) exposure on pregnancy such as increasing the risk of pre-eclampsia, epidemiological evidence is limited. We aimed to evaluate the relationship between maternal BPA exposure and the risk of pre-eclampsia. Methods We conducted a nested case–control study among 173 women (74 cases of pre-eclampsia and 99 controls). BPA concentrations were measured using liquid chromatography-mass spectrometry in the maternal serum samples collected during 16–20 gestational weeks. Multivariate logistic models were used to examine the relationship between maternal serum BPA concentrations and the risk of pre-eclampsia. Results BPA was detectable (>0.1 µg/l) in 78.6% of the maternal serum samples at three levels: low (4.44 µg/l). BPA concentrations were significantly higher in the serum samples collected from the pre-eclampsia cases than those from controls (median: 3.40 vs. 1.50 µg/l, P < 0.01). With adjustment for maternal age, primiparous and BMI, the odds of developing pre-eclampsia were significantly elevated in subjects with high serum BPA levels compared with those with low levels (adjusted OR = 16.46, 95%CI = 5.42–49.85) regardless of subcategories of pre-eclampsia including severity and onset time. Among the pre-eclampsia subjects, the maternal serum concentration of BPA was not different between the early- and late-onset subjects (median: 3.09 vs. 3.50 µg/l, P = 0.57), but surprisingly higher in mild pre-eclampsia subjects compared with severe pre-eclampsia subjects (median: 5.20 vs. 1.80 µg/l, P < 0.01). Conclusions These results demonstrated that maternal exposure to high level of BPA could be associated with an increased risk of pre-eclampsia. PMID:29186464

  3. Early onset epileptic encephalopathy or genetically determined encephalopathy with early onset epilepsy? Lessons learned from TSC

    NARCIS (Netherlands)

    Curatolo, P.; Aronica, E.; Jansen, A.; Jansen, F.; Kotulska, K.; Lagae, L.; Moavero, R.; Jozwiak, S.

    2016-01-01

    BACKGROUND: In tuberous sclerosis complex (TSC) a relationship has been shown between early and refractory seizures and intellectual disability. However, it is uncertain whether epilepsy in TSC is simply a marker in infants who are destined to develop an encephalopathic process or if seizures play a

  4. Early onset epileptic encephalopathy or genetically determined encephalopathy with early onset epilepsy? Lessons learned from TSC

    NARCIS (Netherlands)

    Curatolo, Paolo; Aronica, Eleonora; Jansen, Anna; Jansen, Floor; Kotulska, Katarzyna; Lagae, Lieven; Moavero, Romina; Jozwiak, Sergiusz

    2016-01-01

    In tuberous sclerosis complex (TSC) a relationship has been shown between early and refractory seizures and intellectual disability. However, it is uncertain whether epilepsy in TSC is simply a marker in infants who are destined to develop an encephalopathic process or if seizures play a causal role

  5. Preeclampsia 2012

    Directory of Open Access Journals (Sweden)

    Elosha Eiland

    2012-01-01

    Full Text Available Preeclampsia is a common complication of pregnancy associated with high maternal morbidity and mortality and intrauterine fetal growth restriction. There is extensive evidence that the reduction of uteroplacental blood flow in this syndrome results from the toxic combination of hypoxia, imbalance of angiogenic and antiangiogenic factors, inflammation, and deranged immunity. Women treated for preeclampsia also have an increased risk for cardiovascular and renal disease. At present it is unclear if the increased cardiovascular and renal disease risks are due to residual and or progressive effects of endothelial damage from the preeclampsia or from shared risk factors between preeclampsia and cardiac disease. Moreover, it appears that endothelin-1 signaling may play a central role in the hypertension associated with preeclampsia. In this paper, we discuss emerging data on the pathogenesis of preeclampsia and review therapeutic options.

  6. Structural brain abnormalities in early onset first-episode psychosis

    DEFF Research Database (Denmark)

    Pagsberg, A K; Baaré, William Frans Christian; Raabjerg Christensen, A M

    2007-01-01

    BACKGROUND: Brain morphometry in children and adolescents with first-episode psychosis offer a unique opportunity for pathogenetic investigations. METHODS: We compared high-resolution 3D T1-weighted magnetic resonance images of the brain in 29 patients (schizophrenia, schizotypal disorder...... that schizophrenia patients (n = 15) had significantly larger lateral ventricles as compared to controls. Duration and dose of antipsychotics correlated negatively with global gray matter volume in minimally medicated patients (n = 18). CONCLUSION: Findings of white matter changes and enlarged lateral ventricles...... already at illness onset in young schizophrenia spectrum patients, suggests aberrant neurodevelopmental processes in the pathogenesis of these disorders. Gray matter volume changes, however, appear not to be a key feature in early onset first-episode psychosis....

  7. Early-onset Hirayama disease in a female

    Directory of Open Access Journals (Sweden)

    Matthias Baumann

    2017-01-01

    Full Text Available Objectives: Hirayama disease is a rare myelopathy, occurring predominantly in males with onset in the teens. Methods and results: Here, we report a young female patient who developed the first signs of Hirayama disease at 10.5 years of age. Prior to onset, she had experienced a growth spurt and grew about 8 cm. The disease progressed over 3 years and the typical clinical, electrophysiological, and neuroimaging signs of Hirayama disease were found. After this period and achievement of her final height, no further progression was noticed. Conclusions: This case highlights that pediatric neurologists should be aware of Hirayama disease, which can also occur in girls in early adolescence.

  8. Conversion (dissociative) symptoms as a presenting feature in early onset bipolar disorder: a case series

    OpenAIRE

    Ghosal, Malay Kumar; Guha, Prathama; Sinha, Mausumi; Majumdar, Debabrata; Sengupta, Payel

    2009-01-01

    We present three cases of early onset bipolar disorder where dissociative (conversion) symptoms preceded the onset of mania. This case series underscores the significance of dissociative/conversion symptoms as an early atypical presentation in juvenile bipolar disorder.

  9. Genetics Home Reference: inclusion body myopathy with early-onset Paget disease and frontotemporal dementia

    Science.gov (United States)

    ... Share: Email Facebook Twitter Home Health Conditions IBMPFD Inclusion body myopathy with early-onset Paget disease and ... Javascript to view the expand/collapse boxes. Description Inclusion body myopathy with early-onset Paget disease and ...

  10. Comprehensive analysis of preeclampsia-associated DNA methylation in the placenta.

    Directory of Open Access Journals (Sweden)

    Tianjiao Chu

    Full Text Available A small number of recent reports have suggested that altered placental DNA methylation may be associated with early onset preeclampsia. It is important that further studies be undertaken to confirm and develop these findings. We therefore undertook a systematic analysis of DNA methylation patterns in placental tissue from 24 women with preeclampsia and 24 with uncomplicated pregnancy outcome.We analyzed the DNA methylation status of approximately 27,000 CpG sites in placental tissues in a massively parallel fashion using an oligonucleotide microarray. Follow up analysis of DNA methylation at specific CpG loci was performed using the Epityper MassArray approach and high-throughput bisulfite sequencing.Preeclampsia-specific DNA methylation changes were identified in placental tissue samples irrespective of gestational age of delivery. In addition, we identified a group of CpG sites within specific gene sequences that were only altered in early onset-preeclampsia (EOPET although these DNA methylation changes did not correlate with altered mRNA transcription. We found evidence that fetal gender influences DNA methylation at autosomal loci but could find no clear association between DNA methylation and gestational age.Preeclampsia is associated with altered placental DNA methylation. Fetal gender should be carefully considered during the design of future studies in which placental DNA is analyzed at the level of DNA methylation. Further large-scale analyses of preeclampsia-associated DNA methylation are necessary.

  11. Polycystic ovary syndrome and early-onset preeclampsia : reproductive manifestations of increased cardiovascular risk

    NARCIS (Netherlands)

    Veltman-Verhulst, Susanne M.; van Rijn, Bas B.; Westerveld, H. Egbertine; Franx, Arie; Bruinse, Hein W.; Fauser, Bart C. J. M.; Goverde, Angelique J.

    2010-01-01

    Objective: Primary prevention of cardiovascular disease (CVD) in women is a major healthcare issue. Detection of premenopausal women with increased risk of CVD could enhance prevention strategies and reduce first event-related morbidity and mortality. In this study, we argue that an unfavorable

  12. INFLAMMATORY BOWEL DISEASE WITH A VERY EARLY ONSET

    Directory of Open Access Journals (Sweden)

    E. A. Kornienko

    2016-01-01

    Full Text Available Inflammatory bowel disease (Crohn's disease and ulcerative colitis has a tendency to manifest at earlier age. In childhood (< 6 years of age it has an especially severe course and is characterized by high grade inflammation, predominantly in the colon, by complication and extra-intestinal autoimmune injury. At younger age, Crohn's disease and ulcerative colitis require more aggressive treatment with frequently poor results. From genetic point of view, monogenic mutations controlling the immune response are characteristic for these diseases with an early onset; therefore, they are frequently associated with primary immunodeficiency. This implies various immunologic deficits, such as breakdown of the epithelial barrier, phagocytic dysfunction and dysfunction of Т and В lymphocytes and regulatory Т cells. Depending on this, a number of primary immunodeficiencies are identified associated with monogenic mutations of more than 50 genes. There some age-related specific features at manifestation. Thus, defects in interleukin 10 and FOXP3 manifest in the first months of life, whereas severe combined immunodeficiencies and phagocytosis defects become evident somewhat later. Virtually all 24 children with very early onset of inflammatory bowel disease, whom we examined, had immunologic defects and one child had a XIAP gene mutation. After identification of a specific immunologic defect, one can understand the mechanism of the disease and suspect one or another genetic defect with subsequent reasonable assessment of mutations in candidate genes. Detection of immunologic and genetic defects in children with a very early onset of inflammatory bowel disease allows for choosing an adequate strategy of non-conventional treatment that may differ depending on the mechanism of the disease.

  13. Early-onset anorexia nervosa in girls with Asperger syndrome

    Directory of Open Access Journals (Sweden)

    Dudova I

    2015-07-01

    Full Text Available Iva Dudova, Jana Kocourkova, Jiri Koutek Department of Child Psychiatry, Charles University Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic Abstract: Eating disorders frequently occur in conjunction with autism spectrum disorders, posing diagnostic and therapeutic difficulties. The comorbidity of anorexia nervosa and Asperger syndrome is a significant clinical complication and has been associated with a poorer prognosis. The authors are presenting the cases of an eleven-year-old girl and a five-and-a-half-year-old girl with comorbid eating disorders and Asperger syndrome. Keywords: eating disorders, early-onset anorexia nervosa, autism spectrum disorders, Asperger syndrome, diagnostics, therapy

  14. Early Onset Childhood Obesity and Risk of Metabolic Syndrome

    Centers for Disease Control (CDC) Podcasts

    2017-10-09

    This podcast features Lorena Pacheco, a doctoral student at the University of California San Diego and one of the winners of PCD’s 2017 Student Research Paper Contest. Lorena answers questions about her winning research, which focuses on the relationship between early onset obesity as a risk factor for increased metabolic syndrome in Chilean children.  Created: 10/9/2017 by Preventing Chronic Disease (PCD), National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 10/9/2017.

  15. Cardiac diastolic function after recovery from pre-eclampsia.

    Science.gov (United States)

    Soma-Pillay, P; Louw, M C; Adeyemo, A O; Makin, J; Pattinson, R C

    Pre-eclampsia is associated with significant changes to the cardiovascular system during pregnancy. Eccentric and concentric remodelling of the left ventricle occurs, resulting in impaired contractility and diastolic dysfunction. It is unclear whether these structural and functional changes resolve completely after delivery. The objective of the study was to determine cardiac diastolic function at delivery and one year post-partum in women with severe pre-eclampsia, and to determine possible future cardiovascular risk. This was a descriptive study performed at Steve Biko Academic Hospital, a tertiary referral hospital in Pretoria, South Africa. Ninety-six women with severe preeclampsia and 45 normotensive women with uncomplicated pregnancies were recruited during the delivery admission. Seventy-four (77.1%) women in the pre-eclamptic group were classified as a maternal near miss. Transthoracic Doppler echocardiography was performed at delivery and one year post-partum. At one year post-partum, women with pre-eclampsia had a higher diastolic blood pressure (p = 0.001) and body mass index (p = 0.02) than women in the normotensive control group. Women with early onset pre-eclampsia requiring delivery prior to 34 weeks' gestation had an increased risk of diastolic dysfunction at one year post-partum (RR 3.41, 95% CI: 1.11-10.5, p = 0.04) and this was irrespective of whether the patient had chronic hypertension or not. Women who develop early-onset pre-eclampsia requiring delivery before 34 weeks are at a significant risk of developing cardiac diastolic dysfunction one year after delivery compared to normotensive women with a history of a low-risk pregnancy.

  16. Cerebellar ataxia of early onset. Clinical symptoms and MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Yamashita, Sumimasa; Miyake, Shota; Yamada, Michiko; Iwamoto, Hiroko (Kanagawa Children' s Medical Center, Yokohama (Japan)); Yamada, Kazuhiko

    1989-07-01

    Eight cases of childhood cerebellar ataxia were reported. All these cases showed chronic cerebellar ataxia with early onset, and the other diseases of cerebellum such as infections, neoplasms and storage diseases were excluded by clinical symptoms and laboratory findings including blood counts, blood chemistry, lactate, pyruvate, ceruloplasmine, urinalysis, serum immunoglobulins, amino acid analysis in blood and urine, CSF analysis, leukocyte lysosomal enzymes, MCV, EMG, EEG and brain X-CT. Two pairs of siblings were included in this study. The clinical diagnosis were cerebellar type (5), spinocerebellar type (1), one Marinesco-Sjoegren syndrome and undetermined type (1). The age of onset was 1 to 5 years. The chief complaint was motor developmental delay in 6 cases; among them 5 patients could walk alone at the ages of 2 to 3 years'. Mental retardation was observed in 7 cases and epilepsy in 2. TRH was effective in 5 cases. The MRI study revealed that the area of medial sagittal slice of the cerebellum was reduced significantly in all cases and also that of pons was reduced in 5 cases. Different from typical adult onset spinocerebellar degenerations, most of the present cases have achieved slow developmental milestones and the clinical course was not progressive. Genetic factors are suspected in the pathogenesis of this disease in some cases. (author).

  17. Historical evolution of ideas on eclampsia/preeclampsia: A proposed optimistic view of preeclampsia.

    Science.gov (United States)

    Robillard, Pierre-Yves; Dekker, Gustaaf; Chaouat, Gérard; Scioscia, Marco; Iacobelli, Silvia; Hulsey, Thomas C

    2017-09-01

    Eclampsia (together with epilepsy) being the first disease ever written down since the beginning of writings in mankind 5000 years ago, we will make a brief presentation of the different major steps in comprehension of Pre-eclampsia. 1) 1840. Rayer, description of proteinuria in eclampsia, 2) 1897 Vaquez, discovery of gestational hypertension in eclamptic women, 3) In the 1970's, description of the "double" trophoblastic invasion existing only in humans (Brosens & Pijnenborg,), 4) between the 1970's and the 1990's, description of preeclampsia being a couple disease. The "paternity problem" (and therefore irruption of immunology), 5) at the end of the 1980's, a major step forward: Preeclampsia being a global endothelial cell disease (glomeruloendotheliosis, hepatic or cerebral endotheliosis, HELLP, eclampsia), inflammation (J.Roberts.C Redman, R Taylor), 6) End of the 1990's: Consensus for a distinction between early onset preeclampsia EOP and late onset LOP (34 weeks gestation), EOP being rather a problem of implantation of the trophoblast (and the placenta), LOP being rather a pre-existing maternal problem (obesity, diabetes, coagulopathies etc…). LOP is predominant everywhere on this planet, but enormously predominant in developed countries: 90% of cases. This feature is very different in countries where women have their first child very young (88% of world births), where the fatal EOP (early onset) occurs in more than 30% of cases. 7) What could be the common factor which could explain the maternal global endotheliosis in EOP and LOP? Discussion about the inositol phospho glycans P type. Copyright © 2017. Published by Elsevier B.V.

  18. Risk of preeclampsia after gestational exposure to selective serotonin reuptake inhibitors and other antidepressants: A study from The Norwegian Mother and Child Cohort Study.

    Science.gov (United States)

    Lupattelli, Angela; Wood, Mollie; Lapane, Kate; Spigset, Olav; Nordeng, Hedvig

    2017-10-01

    To describe the risk of early- and late-onset preeclampsia across pregnancies exposed to antidepressants and to evaluate the impact of timing and length of gestational exposure to antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), on preeclampsia. The Norwegian Mother and Child Cohort, a prospective population-based study, and the Medical Birth Registry of Norway provided information on antidepressant exposure, depression, and anxiety symptoms in pregnancy, preeclampsia diagnoses, and important covariates. Within a pregnancy cohort of depressed women, we compared the risk of late-onset preeclampsia between SSRI-exposed and nonmedicated pregnancies using marginal structural models (weighted) and modified Poisson regression models. Of the 5887 pregnancies included, 11.1% were exposed at any time before week 34 to SSRIs, 1.3% to serotonin-norepinephrine reuptake inhibitors, 0.4% to tricyclic antidepressants, and 0.5% to other antidepressants. The risks of early- and late-onset preeclampsia by exposure status in pregnancy were 0.3% and 3.6% (nonmedicated), 0.4% and 3.7% (SSRIs), 1.5% and 4.1% (serotonin-norepinephrine reuptake inhibitors), and 7.1% and 10.0% (tricyclic antidepressants). Compared with nonmedicated pregnancies, SSRI-exposed in mid and late gestation had adjusted relative risks for late-onset mild preeclampsia of 0.76 (95% confidence interval, 0.38-1.53) and 1.56 (0.71-3.44) (weighted models), respectively. There was no association between SSRI exposure in pregnancy and severe late-onset preeclampsia. We have provided evidence that SSRI use in early and midpregnancy does not substantially increase the risk of late-onset preeclampsia. © 2017 The Authors. Pharmacoepidemiology & Drug Safety published by John Wiley & Sons Ltd.

  19. Diagnosis of preeclampsia with soluble Fms-like tyrosine kinase 1/placental growth factor ratio

    DEFF Research Database (Denmark)

    Andersen, Louise Bjørkholt; Frederiksen-Møller, Britta; Work Havelund, Kathrine

    2015-01-01

    women (n = 39) were included shortly after the time of diagnosis. Normotensive control pregnancies were matched by gestational age (n = 76). The KRYPTOR assays performed comparably or superior to Elecsys (sFlt-1/PlGF area under the curve 0.746 versus 0.735; P = .09; for non-obese 0.820 versus 0.805, P...... = .047). For early-onset preeclampsia, KRYPTOR area under the curve increased to 0.929 with a 100% specificity for preeclampsia at cut-off 85 and an 88.9% sensitivity for preeclampsia at cut-off 33. For women with preeclampsia and preterm delivery or Hemolysis, Elevated Liver enzymes, Low Platelet count...... (HELLP) syndrome, the KRYPTOR sFlt-1/PlGF ratio was manifold increased (P women....

  20. Early onset neonatal sepsis in preterm premature rupture of membranes

    International Nuclear Information System (INIS)

    Ashraf, M.N.

    2015-01-01

    To determine the frequency of early onset neonatal sepsis in newborn with various duration of preterm premature rupture of membranes (PPROM). Study Design: Cross sectional study. Place and Duration of Study: Neonatal Intensive Care Unit Combined Military Hospital, Lahore from November 2009 to November 2010. Material and Methods: Neonates of singleton pregnancies complicated by preterm premature rupture of the membranes (PPROM) with delivery between 30 and 36 weeks gestation were included in the study. The overall frequency of neonatal sepsis was calculated on clinical and serological basis. Comparison of the frequency of sepsis among groups with varying duration of rupture of membranes was done. Results: Out of 164 babies, 84 (51.2%) were female and 80 (48.8%) were male. Mean maternal age was 23 years (range: 18-36 years). Mean gestational age was 33 weeks (range: 30-36 weeks). Sepsis was suspected in 41(25%) babies on clinical grounds. C-reactive protein was raised in 36 (22%) neonates. There was statistically insignificant difference between clinical versus serological diagnosis (p=0.515). Frequency of neonatal sepsis was significantly higher in mothers with longer duration of rupture of membrane (p < 0.001). Conclusion: Frequency of neonatal sepsis was observed to be 22%. PPROM is an important risk factor for early onset neonatal sepsis. (author)

  1. Premature adrenarche: novel lessons from early onset androgen excess.

    Science.gov (United States)

    Idkowiak, Jan; Lavery, Gareth G; Dhir, Vivek; Barrett, Timothy G; Stewart, Paul M; Krone, Nils; Arlt, Wiebke

    2011-08-01

    Adrenarche reflects the maturation of the adrenal zona reticularis resulting in increased secretion of the adrenal androgen precursor DHEA and its sulphate ester DHEAS. Premature adrenarche (PA) is defined by increased levels of DHEA and DHEAS before the age of 8 years in girls and 9 years in boys and the concurrent presence of signs of androgen action including adult-type body odour, oily skin and hair and pubic hair growth. PA is distinct from precocious puberty, which manifests with the development of secondary sexual characteristics including testicular growth and breast development. Idiopathic PA (IPA) has long been considered an extreme of normal variation, but emerging evidence links IPA to an increased risk of developing the metabolic syndrome (MS) and thus ultimately cardiovascular morbidity. Areas of controversy include the question whether IPA in girls is associated with a higher rate of progression to the polycystic ovary syndrome (PCOS) and whether low birth weight increases the risk of developing IPA. The recent discoveries of two novel monogenic causes of early onset androgen excess, apparent cortisone reductase deficiency and apparent DHEA sulphotransferase deficiency, support the notion that PA may represent a forerunner condition for PCOS. Future research including carefully designed longitudinal studies is required to address the apparent link between early onset androgen excess and the development of insulin resistance and the MS.

  2. Early preeclampsia and HELLP syndrome in a 20 week pregnant patient

    Directory of Open Access Journals (Sweden)

    Fatemeh Keighobadi Khajeh

    2017-01-01

    Full Text Available The first time Weinstein in 1982 described patients with the syndrome of hemolysis, elevated liver enzymes, and low platelet count (HELLP in pregnant preeclamptic and eclamptic patients. This syndrome is a severe form of preeclampsia or eclampsia. Usually HELLP syndrome occurs at the third trimester and only 15% occur before the 27th week of pregnancy and rarely before the 20th week of pregnancy. We want to present a 30- year old parity 2, gravidity 1 pregnant patient who was pregnant for 20 weeks with preeclampsia and HELLP syndrome. Two hours before arriving to the emergency unit, she felt chest discomfort and went to the nearest clinic to visit a physician. She was then referred to the hospital because of high blood pressure (BP. When she arrived to the emergency unit, she had right upper quadrant and epigastric pain, headache, vomiting, dyspnea, and high BP (185/100. Finally the diagnosis of HELLP syndrome was made. As maternal and fetus mortality and morbidity of HELLP syndrome is high, immediate recognition and treatment is vital to save the lives of both the mother and the fetus

  3. Suicide in later life : A comparison between cases with early-onset and late-onset depression

    NARCIS (Netherlands)

    Voshaar, Richard C. Oude; Kapur, Nay; Bickley, Harriet; Williams, Alyson; Purandare, Nitin

    Background: Suicide rates are high in elderly people with depressive disorder. We compared behavioural, clinical and care characteristics of depressed elderly patients, aged 60 years and over at the time of death by suicide, with an early-onset depression (EOD, onset before 60 years) with those

  4. NEW DEVELOPMENTS IN THE PATHOGENESIS OF PREECLAMPSIA

    OpenAIRE

    Naljayan, Mihran V.; Karumanchi, S. Ananth

    2013-01-01

    Preeclampsia affecting 3-5% of all pregnancies is a major cause of maternal and perinatal morbidity and mortality worldwide. This disorder is characterized by a constellation of signs and symptoms, most notably new onset hypertension and proteinuria during the last trimester of pregnancy. In this review, the molecular mechanisms of preeclampsia with an emphasis on the role of circulating anti-angiogenic proteins in the pathogenesis of preeclampsia and its complications will be discussed.

  5. Differences of neuroimaging between early-onset and late-onset alzheimer-type dementia

    International Nuclear Information System (INIS)

    Hanyu, Haruo; Nakano, Seigo; Abe, Shin'e; Arai, Hisayuki; Iwamoto, Toshihiko; Takasaki, Masaru

    1995-01-01

    Several studies have shown that the symptomatology and the neuropathological and neurochemical changes of early-onset Alzheimer's disease (EAD) differ from those of late-onset Alzheimer's disease (LAD). The aim of the present study is to examine differences in SPECT and MRI findings between EAD and LAD. Cerebral blood flow and patterns on SPECT, and deep white matter lesions and cerebral atrophy on MRI in 17 patients with EAD were compared with 30 patients with LAD without cerebrovascular risk factors. Temporoparietal activity ratio, divided by cerebellum, on SPECT imaging in patients with EAD was significantly lower than in patients with LAD. In a qualitative assessment of perfusion patterns, bilateral temporoparietal hypoperfusion, which is typical in AD, was seen more frequently in patients with EAD than in those with LAD. Among white matter changes in MRI, the score of white matter hyperintensity was significantly higher in LAD than in EAD patients. However, there was no significant difference between periventricular hyperintensity scores. Though ventricular enlargement did not differ significantly in EAD and LAD, cortical atrophy scores in LAD were significantly higher than in EAD. Cortical atrophy scores were significantly higher in patients with atypical perfusion patterns on SPECT (e.g. global hypoperfusion in addition to temporoparietal change) than in patients with typical perfusion pattern. These results indicate that functional and morphological imagings in LAD differ with those in EAD, probably due to less-prominent neuropathological degeneration combined with age-related alterations. (author)

  6. Differences of neuroimaging between early-onset and late-onset alzheimer-type dementia

    Energy Technology Data Exchange (ETDEWEB)

    Hanyu, Haruo; Nakano, Seigo; Abe, Shin` e; Arai, Hisayuki; Iwamoto, Toshihiko; Takasaki, Masaru [Tokyo Medical Coll. (Japan)

    1995-10-01

    Several studies have shown that the symptomatology and the neuropathological and neurochemical changes of early-onset Alzheimer`s disease (EAD) differ from those of late-onset Alzheimer`s disease (LAD). The aim of the present study is to examine differences in SPECT and MRI findings between EAD and LAD. Cerebral blood flow and patterns on SPECT, and deep white matter lesions and cerebral atrophy on MRI in 17 patients with EAD were compared with 30 patients with LAD without cerebrovascular risk factors. Temporoparietal activity ratio, divided by cerebellum, on SPECT imaging in patients with EAD was significantly lower than in patients with LAD. In a qualitative assessment of perfusion patterns, bilateral temporoparietal hypoperfusion, which is typical in AD, was seen more frequently in patients with EAD than in those with LAD. Among white matter changes in MRI, the score of white matter hyperintensity was significantly higher in LAD than in EAD patients. However, there was no significant difference between periventricular hyperintensity scores. Though ventricular enlargement did not differ significantly in EAD and LAD, cortical atrophy scores in LAD were significantly higher than in EAD. Cortical atrophy scores were significantly higher in patients with atypical perfusion patterns on SPECT (e.g. global hypoperfusion in addition to temporoparietal change) than in patients with typical perfusion pattern. These results indicate that functional and morphological imagings in LAD differ with those in EAD, probably due to less-prominent neuropathological degeneration combined with age-related alterations. (author).

  7. Molecular genetics of preeclampsia and HELLP syndrome - A review

    NARCIS (Netherlands)

    Jebbink, Jiska; Wolters, Astrid; Fernando, Febilla; Afink, Gijs; van der Post, Joris; Ris-Stalpers, Carrie

    2012-01-01

    Preeclampsia is characterised by new onset hypertension and proteinuria and is a major obstetrical problem for both mother and foetus. Haemolysis elevated liver enzymes and low platelets (HELLP) syndrome is an obstetrical emergency and most cases occur in the presence of preeclampsia. Preeclampsia

  8. Theory of Mind differences in older patients with early-onset and late-onset paranoid schizophrenia.

    Science.gov (United States)

    Smeets-Janssen, M M J; Meesters, P D; Comijs, H C; Eikelenboom, P; Smit, J H; de Haan, L; Beekman, A T F; Stek, M L

    2013-11-01

    Theory of Mind (ToM) is considered an essential element of social cognition. In younger schizophrenia patients, ToM impairments have extensively been demonstrated. It is not clear whether similar impairments can be found in older schizophrenia patients and if these impairments differ between older patients with early-onset and late-onset schizophrenia. Theory of Mind abilities were assessed using the Hinting Task in 15 older patients (age 60 years and older) with early-onset paranoid schizophrenia, 15 older patients with late-onset paranoid schizophrenia and 30 healthy controls. ANCOVA was performed to test differences between groups. Analyses were adjusted for level of education. Effect sizes, partial eta squared (ε(2) ), were computed as an indication of the clinical relevance of the findings. Patients with early-onset schizophrenia scored significantly lower on the Hinting Task (mean 16.1; SD 4.3) compared with patients with late-onset schizophrenia (mean 18.6; SD 1.5) and with healthy controls (mean 19.0; SD 1.4). The effect size of this difference was large (ε(2)  = 0.2). These results suggest that ToM functioning may be a protective factor modulating the age at onset of psychosis. Further studies into the relationship between social cognition and onset age of psychosis are warranted. Copyright © 2013 John Wiley & Sons, Ltd.

  9. Pregnancy Complications: Preeclampsia

    Science.gov (United States)

    ... online community Home > Complications & Loss > Pregnancy complications > Preeclampsia Preeclampsia E-mail to a friend Please fill in ... even if you’re feeling fine. What is preeclampsia? Preeclampsia is a serious blood pressure condition that ...

  10. Molecular Mechanisms of Preeclampsia

    OpenAIRE

    N. Vitoratos; D. Hassiakos; C. Iavazzo

    2012-01-01

    Preeclampsia is a pregnancy-specific disease characterized by new onset hypertension and proteinuria after 20 wk of gestation. It is a leading cause of maternal and fetal morbidity and mortality worldwide. Exciting discoveries in the last decade have contributed to a better understanding of the molecular basis of this disease. Epidemiological, experimental, and therapeutic studies from several laboratories have provided compelling evidence that an antiangiogenic state owing to alterations in ...

  11. Rapid onset of efficacy of rasagiline in early Parkinson's disease.

    Science.gov (United States)

    Zambito Marsala, Sandro; Vitaliani, Roberta; Volpe, Daniele; Capozzoli, Francesca; Baroni, Luciana; Belgrado, Enrico; Borsato, Carlo; Gioulis, Manuela; Marchini, Corrado; Antonini, Angelo

    2013-11-01

    Rasagiline is a monoamine oxidase type-B inhibitor used as monotherapy or in addition to levodopa in the treatment of Parkinson's disease (PD). This naturalistic single-blind study was aimed at evaluating the rapidity of onset effect of rasagiline on motor symptoms in a cohort of early relatively elderly PD patients. 102 outpatients (55 males, median age 71 years) have been selected: 26 were PD therapy-naive and 76 received rasagiline as add-on therapy. The third section of the Unified Parkinson's Disease Rating Scale (UPDRSIII) and the Hoehn-Yahr (HY) scale were assessed at baseline and after 1 and 4 weeks thereafter. The mean UPDRS III total score (-6.7 at week 1 and -8.9 at week 4) and single items, as well as mean HY score (-0.40 at week 1 and -0.67 at week 4), significantly decreased from baseline (p or ≤71 years. Rasagiline had a rapid therapeutic effect from the first week of therapy, which further improved at 4 weeks. The rapid onset of action and the absence of a dose titration are important issues in the management of the PD patient.

  12. [Clinical characteristics and renal uric acid excretion in early-onset gout patients].

    Science.gov (United States)

    Li, Q H; Liang, J J; Chen, L X; Mo, Y Q; Wei, X N; Zheng, D H; Dai, L

    2018-03-01

    Objective: To investigate clinical characteristics and renal uric acid excretion in early-onset gout patients. Methods: Consecutive inpatients with primary gout were recruited between 2013 and 2017. The patients with gout onset younger than 30 were defined as early-onset group while the others were enrolled as control group. Clinical characteristics and uric acid (UA) indicators were compared between two groups. Results: Among 202 recruited patients, the early-onset group included 36 patients (17.8%). Compared with control group, the early-onset group presented more patients with obesity [13 patients (36.1%) vs. 22 patients (13.3%), Pgout early onset. Conclusion: The gout patients with early-onset younger than 30 present high serum and glomerular load of uric acid which might be due to obesity and relative under-excretion of renal uric acid.

  13. Single administration of ultra-low-dose lipopolysaccharide in rat early pregnancy induces TLR4 activation in the placenta contributing to preeclampsia.

    Directory of Open Access Journals (Sweden)

    Pingping Xue

    Full Text Available Balanced immune responses are essential for the maintenance of successful pregnancy. Aberrant responses of immune system during pregnancy increase the risk of preeclampsia. Toll-like receptor 4 (TLR4 plays a crucial role in the activation of immune system at the maternal-fetal interface. This study aimed to generate a rat model of preeclampsia by lipopolysaccharide (LPS, a TLR4 agonist administration on gestational day (GD 5 as rats are subjected to placentation immediately after implantation between GDs 4 and 5, and to assess the contribution of TLR4 signaling to the development of preeclampsia. Single administration of 0.5 μg/kg LPS significantly increased blood pressure of pregnant rats since GD 6 (systolic blood pressure, 124.89 ± 1.79 mmHg versus 119.02 ± 1.80 mmHg, P < 0.05 and urinary protein level since GD 9 (2.02 ± 0.29 mg versus 1.11 ± 0.18 mg, P < 0.01, but barely affected blood pressure or proteinuria of virgin rats compared with those of saline-treated pregnant rats. This was accompanied with adverse pregnancy outcomes including fetal growth restriction. The expression of TLR4 and NF-κB p65 were both increased in the placenta but not the kidney from LPS-treated pregnant rats, with deficient trophoblast invasion and spiral artery remodeling. Furthermore, the levels of inflammatory cytokines were elevated systemically and locally in the placenta from pregnant rats treated with LPS. TLR4 signaling in the placenta was activated, to which that in the placenta of humans with preeclampsia changed similarly. In conclusion, LPS administration to pregnant rats in early pregnancy could elicit TLR4-mediated immune response at the maternal-fetal interface contributing to poor early placentation that may culminate in the preeclampsia-like syndrome.

  14. Disturbed Placental Imprinting in Preeclampsia Leads to Altered Expression of DLX5, a Human-Specific Early Trophoblast Marker.

    Science.gov (United States)

    Zadora, Julianna; Singh, Manvendra; Herse, Florian; Przybyl, Lukasz; Haase, Nadine; Golic, Michaela; Yung, Hong Wa; Huppertz, Berthold; Cartwright, Judith E; Whitley, Guy; Johnsen, Guro M; Levi, Giovanni; Isbruch, Annette; Schulz, Herbert; Luft, Friedrich C; Müller, Dominik N; Staff, Anne Cathrine; Hurst, Laurence D; Dechend, Ralf; Izsvák, Zsuzsanna

    2017-11-07

    Preeclampsia is a complex and common human-specific pregnancy syndrome associated with placental pathology. The human specificity provides both intellectual and methodological challenges, lacking a robust model system. Given the role of imprinted genes in human placentation and the vulnerability of imprinted genes to loss of imprinting changes, there has been extensive speculation, but no robust evidence, that imprinted genes are involved in preeclampsia. Our study aims to investigate whether disturbed imprinting contributes to preeclampsia. We first aimed to confirm that preeclampsia is a disease of the placenta by generating and analyzing genome-wide molecular data on well-characterized patient material. We performed high-throughput transcriptome analyses of multiple placenta samples from healthy controls and patients with preeclampsia. Next, we identified differentially expressed genes in preeclamptic placentas and intersected them with the list of human imprinted genes. We used bioinformatics/statistical analyses to confirm association between imprinting and preeclampsia and to predict biological processes affected in preeclampsia. Validation included epigenetic and cellular assays. In terms of human specificity, we established an in vitro invasion-differentiation trophoblast model. Our comparative phylogenetic analysis involved single-cell transcriptome data of human, macaque, and mouse preimplantation embryogenesis. We found disturbed placental imprinting in preeclampsia and revealed potential candidates, including GATA3 and DLX5 , with poorly explored imprinted status and no prior association with preeclampsia. As a result of loss of imprinting, DLX5 was upregulated in 69% of preeclamptic placentas. Levels of DLX5 correlated with classic preeclampsia markers. DLX5 is expressed in human but not in murine trophoblast. The DLX5 high phenotype resulted in reduced proliferation, increased metabolism, and endoplasmic reticulum stress-response activation in

  15. Correlates and prevalence of hypogonadism in patients with early- and late-onset type 2 diabetes.

    Science.gov (United States)

    Li, Y; Zhang, M; Liu, X; Cui, W; Rampersad, S; Li, F; Lin, Z; Yang, P; Li, H; Sheng, C; Cheng, X; Qu, S

    2017-07-01

    This study aims to compare the prevalence of hypogonadism between male patients with early-onset type 2 diabetes mellitus (T2DM) and late-onset type 2 diabetes. A total of 122 male patients with early-onset T2DM (diagnosis age ≤40 years) and 100 male patients with late-onset T2DM (diagnosis age >40 years) were recruited from our in-patient department between 1 January 2013 and 28 December 2015. Serum FSH, LH, testosterone, lipid profile, uric acid, HbA1c, and beta-cell function were determined in blood samples. The diagnosis of hypogonadism was based on the levels of LH, FSH, and total testosterone. The mean onset age was 29.86 ± 6.31 and 54.47 ± 9.97 years old in the early-onset group and late-onset group, respectively. Compared with late-onset T2DM, those with early-onset T2DM had a higher proportion of new-onset diabetes, were more likely to be obese, and had worse glycemic control, lipid control, and lower sex hormone-binding globulin (SHBG). The prevalence of hypogonadism was much higher in the early-onset group than in the late-onset group (48.0% vs. 26.7%, p hypogonadism in the early-onset group and late-onset group were 44.3% and 25.0%, respectively (p hypogonadism was higher in the patients with early-onset T2DM than that of late-onset T2DM. This prevalence might be attributable to greater obesity, worse lipid control, and lower SHBG levels in those patients. © 2017 American Society of Andrology and European Academy of Andrology.

  16. Incidence of early-onset dementia in Mar del Plata.

    Science.gov (United States)

    Sanchez Abraham, M; Scharovsky, D; Romano, L M; Ayala, M; Aleman, A; Sottano, E; Etchepareborda, I; Colla Machado, C; García, M I; Gonorazky, S E

    2015-03-01

    Early-onset dementia (EOD) is defined as dementia with onset before the age of 65 years. EOD is increasingly recognised as an important clinical and social problem with devastating consequences for patients and caregivers. Determine the annual crude incidence rate and the specific incidence rates by sex and age in patients with EOD, and the standardised rate using the last national census of the population of Argentina (NCPA), from 2010. Hospital Privado de Comunidad, Mar del Plata, Argentina, attends a closed population and is the sole healthcare provider for 17 614 people. Using the database pertaining to the Geriatric Care department, we identified all patients diagnosed with EOD between 1 January, 2005 and 31 December, 2011. EOD was defined as dementia diagnosed in patients younger than 65. The study period yielded 14 patients diagnosed with EOD out of a total of 287 patients evaluated for memory concerns. The crude annual incidence of EOD was 11 per 100 000/year (CI 95%: 6.25-19.1): 17 per 100 000 (CI 95%: 7.2-33.1) in men and 8 per 100 000 (CI 95%: 3.4-17.2) in women. We observed a statistically significant increase when comparing incidence rates between patients aged 21 to <55 years and ≥ 55 to <65 years (3 vs 22 per 100 000, P=.0014). The rate adjusted by NCPA census data was 5.8 cases of EOD habitants/year. This study, conducted in a closed population, yielded an EOD incidence rate of 11 per 100 000 inhabitants/year. To the best of our knowledge, this is the first prospective epidemiological study in Argentina and in Latin America. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  17. Maternal and fetal alternative complement pathway activation in early severe preeclampsia.

    Science.gov (United States)

    Hoffman, M Camille; Rumer, Kristen K; Kramer, Anita; Lynch, Anne M; Winn, Virginia D

    2014-01-01

    We sought to determine whether alternative complement activation fragment Bb (Bb) levels are elevated in the maternal, fetal, and placental blood in cases of severe preeclampsia (PE) compared with normotensive controls. This was a cross-sectional study of women admitted at ≥24 weeks gestation with or without severe PE. Maternal plasma was collected at the time of enrollment. Umbilical venous cord and intervillous space blood were collected at delivery. Plasma Bb levels were assessed using ELISA. Bb levels were compared between cases and controls. Median Bb levels were higher in the maternal plasma of severe PE subjects (n = 24) than in controls (n = 20), 1.45 ± 1.03 versus 0.65 ± 0.23 μg/mL, P < 0.001. In umbilical venous plasma, Bb levels were higher in severe PE subjects (n = 15) compared with controls (n = 15), 2.48 ± 1.40 versus 1.01 ± 0.57 μg/mL, P = 0.01. Activation fragment Bb is increased in the maternal and umbilical venous blood of cases of severe PE when compared with normotensive controls. These data provide support for alternative complement pathway involvement in the pathogenesis of severe PE and demonstrate that alternative complement activation occurs not only in the maternal but also in the fetal compartment. © 2013 John Wiley & Sons Ltd.

  18. Hypothalamic-pituitary-adrenal axis activity and early onset of cannabis use

    NARCIS (Netherlands)

    Huizink, Anja C.; Ferdinand, Robert F.; Ormel, Johan; Verhulst, Frank C.

    Aims To identify early onset cannabis users by measuring basal hypothalamic-pituitary-adrenal (HPA) axis activity, which may be a risk factor for early onset substance use when showing low activity. Design In a prospective cohort study, adolescents who initiated cannabis use at an early age (9-12

  19. Clinical correlates of first episode early onset psychosis in KwaZulu ...

    African Journals Online (AJOL)

    Background: The study of first episode early onset psychosis can yield many clues to understanding the early development of psychosis and guide interventions to decrease psychosis risk and improve outcome. The aim of the study was to investigate the socio-demographic profile and clinical correlates in early onset ...

  20. Hypothalamic-pituitary-adrenal axis activity and early onset of cannabis use

    NARCIS (Netherlands)

    Huizink, Anja C.; Ferdinand, Robert F.; Ormel, Johan; Verhulst, Frank C.

    2006-01-01

    Aims To identify early onset cannabis users by measuring basal hypothalamic-pituitary-adrenal (HPA) axis activity, which may be a risk factor for early onset substance use when showing low activity. Design In a prospective cohort study, adolescents who initiated cannabis use at an early age (9-12

  1. Neurocognition in early-onset schizophrenia and schizoaffective disorders.

    Science.gov (United States)

    Hooper, Stephen R; Giuliano, Anthony J; Youngstrom, Eric A; Breiger, David; Sikich, Linmarie; Frazier, Jean A; Findling, Robert L; McClellan, Jon; Hamer, Robert M; Vitiello, Benedetto; Lieberman, Jeffrey A

    2010-01-01

    We examined the neuropsychological functioning of youth enrolled in the NIMH funded trial, Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS). We compared the baseline neuropsychological functioning of youth with schizophrenia (SZ, n = 79) to those with schizoaffective disorder (SA, n = 40), and examined the relationship of different variables of illness severity and adaptive behavior to neuropsychological functioning. Participants ranged in age from 8 to 19 years. Diagnostic status was confirmed via structured interview over multiple time points. Domains of neuropsychological functioning included fine-motor, attention, working memory, problem-solving efficiency, inhibitory control, and social cognition. Other variables included intelligence (IQ), academic achievement skills, adaptive behavior, and different measures of illness severity. The two groups did not differ on IQ or on any of the neuropsychological domains. The SZ group performed significantly lower in spelling. A high proportion of individuals in both groups reflected significant intellectual and academic achievement skill deficits. Significant correlations were found between the neurocognitive domains and both illness severity and adaptive behavior variables. There were few differences between the SZ and SA groups on IQ, achievement, or neuropsychological functioning; however, both groups showed significantly high rates of deficits in IQ and basic academic skills. Correlations of the neurocognitive functions with illness severity and adaptive behavior were small to moderate in magnitude. These findings continue to implicate the importance of neurocognitive functioning as a key area of vulnerability in the study of youth with schizophrenia spectrum disorders.

  2. Psychosocial impact of early onset dementia among caregivers

    Directory of Open Access Journals (Sweden)

    Nathália R. S. Kimura

    2015-12-01

    Full Text Available Introduction: There is growing recognition of early onset dementia (EOD as a significant clinical and social problem because of its effects on physical and mental health of people with dementia (PWD and their caregivers. Objective: To analyze the psychosocial impact of EOD in family caregivers. Methods: The study design was qualitative. Nine EOD caregivers (7 women were recruited at a service for Alzheimer's disease and assessed using semi-structured interviews. Interpretative phenomenological analysis was used to analyze caregivers' reports. Results: Five themes emerged from the narratives: psychological and emotional impact; physical impact; financial and professional impact; social impact and need for support services. The majority of the caregivers of people with EOD perceived their emotional wellbeing as poor or extremely poor. Carers reported poor physical health, which tends to be longer-lasting than mental health problems. Two caregivers had to retire after the disclosure of the dementia diagnosis, and seven reduced their work loads because they had to look after PWD. Preserving the abilities of PWD is essential to maintain their self-esteem, dignity and sense of utility. For the caregivers, interventions and stimulating activities make PWD feel worthwhile and contribute to improving life. Conclusion: The caregivers of people with EOD assume the role of caregiver prematurely and need to balance this activity with other responsibilities. There is a need for more studies of EOD in order to improve understanding of the impact of this disease and to enable development of adequate services for PWD and their caregivers.

  3. Facial emotion identification in early-onset psychosis.

    Science.gov (United States)

    Barkl, Sophie J; Lah, Suncica; Starling, Jean; Hainsworth, Cassandra; Harris, Anthony W F; Williams, Leanne M

    2014-12-01

    Facial emotion identification (FEI) deficits are common in patients with chronic schizophrenia and are strongly related to impaired functioning. The objectives of this study were to determine whether FEI deficits are present and emotion specific in people experiencing early-onset psychosis (EOP), and related to current clinical symptoms and functioning. Patients with EOP (n=34, mean age=14.11, 53% female) and healthy controls (HC, n=42, mean age 13.80, 51% female) completed a task of FEI that measured accuracy, error pattern and response time. Relative to HC, patients with EOP (i) had lower accuracy for identifying facial expressions of emotions, especially fear, anger and disgust, (ii) were more likely to misattribute other emotional expressions as fear or disgust, and (iii) were slower at accurately identifying all facial expressions. FEI accuracy was not related to clinical symptoms or current functioning. Deficits in FEI (especially for fear, anger and disgust) are evident in EOP. Our findings suggest that while emotion identification deficits may reflect a trait susceptibility marker, functional deficits may represent a sequelae of illness. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Molecular genetics of early-onset Alzheimer's disease revisited.

    Science.gov (United States)

    Cacace, Rita; Sleegers, Kristel; Van Broeckhoven, Christine

    2016-06-01

    As the discovery of the Alzheimer's disease (AD) genes, APP, PSEN1, and PSEN2, in families with autosomal dominant early-onset AD (EOAD), gene discovery in familial EOAD came more or less to a standstill. Only 5% of EOAD patients are carrying a pathogenic mutation in one of the AD genes or a apolipoprotein E (APOE) risk allele ε4, most of EOAD patients remain unexplained. Here, we aimed at summarizing the current knowledge of EOAD genetics and its role in ongoing approaches to understand the biology of AD and disease symptomatology as well as developing new therapeutics. Next, we explored the possible molecular mechanisms that might underlie the missing genetic etiology of EOAD and discussed how the use of massive parallel sequencing technologies triggered novel gene discoveries. To conclude, we commented on the relevance of reinvestigating EOAD patients as a means to explore potential new avenues for translational research and therapeutic discoveries. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Psychosocial impact of early onset dementia among caregivers.

    Science.gov (United States)

    Kimura, Nathália R S; Maffioletti, Virgínia L R; Santos, Raquel L; Baptista, Maria Alice Tourinho; Dourado, Marcia C N

    2015-01-01

    There is growing recognition of early onset dementia (EOD) as a significant clinical and social problem because of its effects on physical and mental health of people with dementia (PWD) and their caregivers. To analyze the psychosocial impact of EOD in family caregivers. The study design was qualitative. Nine EOD caregivers (7 women) were recruited at a service for Alzheimer's disease and assessed using semi-structured interviews. Interpretative phenomenological analysis was used to analyze caregivers' reports. Five themes emerged from the narratives: psychological and emotional impact; physical impact; financial and professional impact; social impact and need for support services. The majority of the caregivers of people with EOD perceived their emotional wellbeing as poor or extremely poor. Carers reported poor physical health, which tends to be longer-lasting than mental health problems. Two caregivers had to retire after the disclosure of the dementia diagnosis, and seven reduced their work loads because they had to look after PWD. Preserving the abilities of PWD is essential to maintain their self-esteem, dignity and sense of utility. For the caregivers, interventions and stimulating activities make PWD feel worthwhile and contribute to improving life. The caregivers of people with EOD assume the role of caregiver prematurely and need to balance this activity with other responsibilities. There is a need for more studies of EOD in order to improve understanding of the impact of this disease and to enable development of adequate services for PWD and their caregivers.

  6. Early and Late Onset Side Effects of Photodynamic Therapy

    Directory of Open Access Journals (Sweden)

    Francesco Borgia

    2018-01-01

    Full Text Available Photodynamic Therapy (PDT is a non-invasive treatment successfully used for neoplastic, inflammatory and infectious skin diseases. One of its strengths is represented by the high safety profile, even in elderly and/or immuno-depressed subjects. PDT, however, may induce early and late onset side effects. Erythema, pain, burns, edema, itching, desquamation, and pustular formation, often in association with each other, are frequently observed in course of exposure to the light source and in the hours/days immediately after the therapy. In particular, pain is a clinically relevant short-term complication that also reduces long-term patient satisfaction. Rare complications are urticaria, contact dermatitis at the site of application of the photosensitizer, and erosive pustular dermatosis. Debated is the relationship between PDT and carcinogenesis: the eruptive appearance of squamous cell carcinoma (SCC in previously treated areas has been correlated to a condition of local and/or systemic immunosuppression or to the selection of PDT-resistant SCC. Here we review the literature, with particular emphasis to the pathogenic hypotheses underlying these observations.

  7. Early Onset Alzheimer’s Disease and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Marco Antonio Meraz-Ríos

    2014-01-01

    Full Text Available Alzheimer’s disease (AD is the most common cause of dementia in elderly adults. It is estimated that 10% of the world’s population aged more than 60–65 years could currently be affected by AD, and that in the next 20 years, there could be more than 30 million people affected by this pathology. One of the great challenges in this regard is that AD is not just a scientific problem; it is associated with major psychosocial and ethical dilemmas and has a negative impact on national economies. The neurodegenerative process that occurs in AD involves a specific nervous cell dysfunction, which leads to neuronal death. Mutations in APP, PS1, and PS2 genes are causes for early onset AD. Several animal models have demonstrated that alterations in these proteins are able to induce oxidative damage, which in turn favors the development of AD. This paper provides a review of many, although not all, of the mutations present in patients with familial Alzheimer’s disease and the association between some of these mutations with both oxidative damage and the development of the pathology.

  8. HLA region excluded by linkage analyses of early onset periodontitis

    Energy Technology Data Exchange (ETDEWEB)

    Sun, C.; Wang, S.; Lopez, N.

    1994-09-01

    Previous studies suggested that HLA genes may influence susceptibility to early-onset periodontitis (EOP). Segregation analyses indicate that EOP may be due to a single major gene. We conducted linkage analyses to assess possible HLA effects on EOP. Fifty families with two or more close relatives affected by EOP were ascertained in Virginia and Chile. A microsatellite polymorphism within the HLA region (at the tumor necrosis factor beta locus) was typed using PCR. Linkage analyses used a donimant model most strongly supported by previous studies. Assuming locus homogeneity, our results exclude a susceptibility gene within 10 cM on either side of our marker locus. This encompasses all of the HLA region. Analyses assuming alternative models gave qualitatively similar results. Allowing for locus heterogeneity, our data still provide no support for HLA-region involvement. However, our data do not statistically exclude (LOD <-2.0) hypotheses of disease-locus heterogeneity, including models where up to half of our families could contain an EOP disease gene located in the HLA region. This is due to the limited power of even our relatively large collection of families and the inherent difficulties of mapping genes for disorders that have complex and heterogeneous etiologies. Additional statistical analyses, recruitment of families, and typing of flanking DNA markers are planned to more conclusively address these issues with respect to the HLA region and other candidate locations in the human genome. Additional results for markers covering most of the human genome will also be presented.

  9. Preeclampsia and health risks later in life: an immunological link.

    Science.gov (United States)

    Cheng, Shi-Bin; Sharma, Surendra

    2016-11-01

    Pregnancy represents a period of physiological stress, and although this stress is experienced for a very modest portion of life, it is now recognized as a window to women's future health, often by unmasking predispositions to conditions that only become symptomatic later in life. In normal pregnancy, the mother experiences mild metabolic syndrome-like condition through week 20 of gestation. A pronounced phenotype of metabolic syndrome may program pregnancy complications such as preeclampsia. Preeclampsia is a serious complication with a myriad of manifestations for mother and offspring. This pregnancy syndrome is a polygenic disease and has been now linked to higher incidence of cardiovascular disease, diabetes, and several other disorders associated with vulnerable organs. Furthermore, the offspring born to preeclamptic mothers also exhibit an elevated risk of cardiovascular disease, stroke, and mental disorders during adulthood. This suggests that preeclampsia not only exposes the mother and the fetus to complications during pregnancy but also programs chronic diseases in later life. The etiology of preeclampsia is thought to be primarily associated with poor placentation and entails excessive maternal inflammation and endothelial dysfunction. It is well established now that the maternal immune system and the placenta are involved in a highly choreographed cross-talk that underlies adequate spiral artery remodeling required for uteroplacental perfusion and free flow of nutrients to the fetus. Since normal pregnancy is associated with a sequence of events represented by temporal events of inflammation (implantation), anti-inflammation (gestation), and inflammation (parturition), it is quite possible that unscheduled alterations in these regulatory responses may lead to pathologic consequences. Although it is not clear whether immunological alterations occur early in pregnancy, it is proposed that dysregulated systemic and placental immunity contribute to impaired

  10. A high concentration of prorenin in early pregnancy is associated with development of pre-eclampsia in women with type 1 diabetes

    DEFF Research Database (Denmark)

    Ringholm, L; Pedersen-Bjergaard, U; Thorsteinsson, B

    2011-01-01

    consecutive pregnant women with type 1 diabetes (median duration 16 years [range 1-36 years], HbA(1c) 6.6% [range 4.9-10.5%]) in early pregnancy. At 8, 14, 21, 27 and 33 weeks and once within 5 days postpartum, blood was sampled for measurements of prorenin, renin, angiotensinogen, ACE and SSAO. HbA(1c...... 4.4 [95% CI 1.5-13.0], p¿=¿0.007), i.e. an increase of prorenin of 100 ng angiotensin I ml(-1) h(-1) implies a 4.4 times higher risk of subsequent pre-eclampsia. CONCLUSIONS/INTERPRETATION: In type 1 diabetic women with pre-eclampsia, a higher concentration of prorenin in early pregnancy and higher......AIMS/HYPOTHESIS: The aim of this study was to investigate whether components of the renin-angiotensin system and semicarbazide-sensitive amine oxidase (SSAO) are associated with the development of pre-eclampsia in women with type 1 diabetes. METHODS: This was an observational study of 107...

  11. Impact of road traffic pollution on pre-eclampsia and pregnancy-induced hypertensive disorders

    DEFF Research Database (Denmark)

    Pedersen, Marie; Halldorsson, Thorhallur I.; Olsen, Sjurdur F.

    2017-01-01

    addresses. Outcome and covariate data were derived from registries, hospital records, and questionnaires. RESULTS: A 10-µg/m increase in NO2 exposure during first trimester was associated with increased risk of preeclampsia (n=1,880, adjusted odds ratio = 1.07 [95% confidence interval = 1.01 to 1.......14]) and pregnancy-induced hypertensive disorders (n=2,430, 1.07 [1.01 to 1.13]). A 10-dBhigher road traffic noise was also associated with increased risk of preeclampsia (1.10 [1.02 to 1.18]) and pregnancy-induced hypertensive disorders (1.08 [1.02 to 1.15]). For both exposures the associations were strongest...... for mild preeclampsia (n=1,393) and early-onset preeclampsia (n=671) while higher risk for severe preeclampsia(n=487) was not evident. In mutually adjusted models estimates for both exposures decreased and only the association between NO2 and mild preeclampsia remained. CONCLUSIONS: Road traffic may...

  12. Early Onset Squamous Cell Carcinoma In A Case Of Lichen Planus

    Directory of Open Access Journals (Sweden)

    Singh Shri Nath

    1998-01-01

    Full Text Available Lichen planus, which is a very common condition, is being presented. However, the uncommon feature in this cases is its early onset and equally early development of squamous cell carcinoma on a lesion on the right thigh.

  13. Deficits in Facial Expression Recognition in Male Adolescents with Early-Onset or Adolescence-Onset Conduct Disorder

    Science.gov (United States)

    Fairchild, Graeme; Van Goozen, Stephanie H. M.; Calder, Andrew J.; Stollery, Sarah J.; Goodyer, Ian M.

    2009-01-01

    Background: We examined whether conduct disorder (CD) is associated with deficits in facial expression recognition and, if so, whether these deficits are specific to the early-onset form of CD, which emerges in childhood. The findings could potentially inform the developmental taxonomic theory of antisocial behaviour, which suggests that…

  14. Verbal and Academic Skills in Children with Early-Onset Type 1 Diabetes

    Science.gov (United States)

    Hannonen, Riitta; Komulainen, Jorma; Eklund, Kenneth; Tolvanen, Asko; Riikonen, Raili; Ahonen, Timo

    2010-01-01

    Aim: Basic verbal and academic skills can be adversely affected by early-onset diabetes, although these skills have been studied less than other cognitive functions. This study aimed to explore the mechanism of learning deficits in children with diabetes by assessing basic verbal and academic skills in children with early-onset diabetes and in…

  15. Hypoxia-activated genes from early placenta are elevated in Preeclampsia, but not in Intra-Uterine Growth Retardation

    Directory of Open Access Journals (Sweden)

    Danan Jean-Louis

    2005-08-01

    Full Text Available Abstract Background As a first step to explore the possible relationships existing between the effects of low oxygen pressure in the first trimester placenta and placental pathologies developing from mid-gestation, two subtracted libraries totaling 2304 cDNA clones were constructed. For achieving this, two reciprocal suppressive/subtractive hybridization procedures (SSH were applied to early (11 weeks human placental villi after incubation either in normoxic or in hypoxic conditions. The clones from both libraries (1440 hypoxia-specific and 864 normoxia-specific were spotted on nylon macroarrays. Complex cDNAs probes prepared from placental villi (either from early pregnancy, after hypoxic or normoxic culture conditions, or near term for controls or pathological placentas were hybridized to the membranes. Results Three hundred and fifty nine clones presenting a hybridization signal above the background were sequenced and shown to correspond to 276 different genes. Nine of these genes are mitochondrial, while 267 are nuclear. Specific expression profiles characteristic of preeclampsia (PE could be identified, as well as profiles specific of intra-uterine growth retardation (IUGR. Focusing on the chromosomal distribution of the fraction of genes that responded in at least one hybridization experiment, we could observe a highly significant chromosomal clustering of 54 genes into 8 chromosomal regions, four of which containing imprinted genes. Comparative mapping data indicate that these imprinted clusters are maintained in synteny in mice, and apparently in cattle and pigs, suggesting that the maintenance of such syntenies is requested for achieving a normal placental physiology in eutherian mammals. Conclusion We could demonstrate that genes induced in PE were also genes highly expressed under hypoxic conditions (P = 5.10-5, which was not the case for isolated IUGR. Highly expressed placental genes may be in syntenies conserved interspecifically

  16. Widespread disruption of functional brain organization in early-onset Alzheimer's disease.

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    Sofie M Adriaanse

    Full Text Available Early-onset Alzheimer's disease (AD patients present a different clinical profile than late-onset AD patients. This can be partially explained by cortical atrophy, although brain organization might provide more insight. The aim of this study was to examine functional connectivity in early-onset and late-onset AD patients. Resting-state fMRI scans of 20 early-onset (<65 years old, 28 late-onset (≥65 years old AD patients and 15 "young" (<65 years old and 31 "old" (≥65 years old age-matched controls were available. Resting-state network-masks were used to create subject-specific maps. Group differences were examined using a non-parametric permutation test, accounting for gray-matter. Performance on five cognitive domains were used in a correlation analysis with functional connectivity in AD patients. Functional connectivity was not different in any of the RSNs when comparing the two control groups (young vs. old controls, which implies that there is no general effect of aging on functional connectivity. Functional connectivity in early-onset AD was lower in all networks compared to age-matched controls, where late-onset AD showed lower functional connectivity in the default-mode network. Functional connectivity was lower in early-onset compared to late-onset AD in auditory-, sensory-motor, dorsal-visual systems and the default mode network. Across patients, an association of functional connectivity of the default mode network was found with visuoconstruction. Functional connectivity of the right dorsal visual system was associated with attention across patients. In late-onset AD patients alone, higher functional connectivity of the sensory-motor system was associated with poorer memory performance. Functional brain organization was more widely disrupted in early-onset AD when compared to late-onset AD. This could possibly explain different clinical profiles, although more research into the relationship of functional connectivity and cognitive

  17. Meta-Analysis and Systematic Review to Assess the Role of Soluble FMS-Like Tyrosine Kinase-1 and Placenta Growth Factor Ratio in Prediction of Preeclampsia: The SaPPPhirE Study.

    Science.gov (United States)

    Agrawal, Swati; Cerdeira, Ana Sofia; Redman, Christopher; Vatish, Manu

    2018-02-01

    Preeclampsia is a major cause of morbidity and mortality worldwide. Numerous candidate biomarkers have been proposed for diagnosis and prediction of preeclampsia. Measurement of maternal circulating angiogenesis biomarker as the ratio of sFlt-1 (soluble FMS-like tyrosine kinase-1; an antiangiogenic factor)/PlGF (placental growth factor; an angiogenic factor) reflects the antiangiogenic balance that characterizes incipient or overt preeclampsia. The ratio increases before the onset of the disease and thus may help in predicting preeclampsia. We conducted a meta-analysis to explore the predictive accuracy of sFlt-1/PlGF ratio in preeclampsia. We included 15 studies with 534 cases with preeclampsia and 19 587 controls. The ratio has a pooled sensitivity of 80% (95% confidence interval, 0.68-0.88), specificity of 92% (95% confidence interval, 0.87-0.96), positive likelihood ratio of 10.5 (95% confidence interval, 6.2-18.0), and a negative likelihood ratio of 0.22 (95% confidence interval, 0.13-0.35) in predicting preeclampsia in both high- and low-risk patients. Most of the studies have not made a distinction between early- and late-onset disease, and therefore, the analysis for it could not be done. It can prove to be a valuable screening tool for preeclampsia and may also help in decision-making, treatment stratification, and better resource allocation. © 2017 American Heart Association, Inc.

  18. Genetics Home Reference: preeclampsia

    Science.gov (United States)

    ... Share: Email Facebook Twitter Home Health Conditions Preeclampsia Preeclampsia Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Preeclampsia is a complication of pregnancy in which affected ...

  19. Early onset facioscapulohumeral dystrophy - a systematic review using individual patient data.

    Science.gov (United States)

    Goselink, Rianne J M; Voermans, Nicol C; Okkersen, Kees; Brouwer, Oebele F; Padberg, George W; Nikolic, Ana; Tupler, Rossella; Dorobek, Malgorzata; Mah, Jean K; van Engelen, Baziel G M; Schreuder, Tim H A; Erasmus, Corrie E

    2017-12-01

    Infantile or early onset is estimated to occur in around 10% of all facioscapulohumeral dystrophy (FSHD) patients. Although small series of early onset FSHD patients have been reported, comprehensive data on the clinical phenotype is missing. We performed a systematic literature search on the clinical features of early onset FSHD comprising a total of 43 articles with individual data on 227 patients. Additional data from four cohorts was provided by the authors. Mean age at reporting was 18.8 years, and 40% of patients were wheelchair-dependent at that age. Half of the patients had systemic features, including hearing loss (40%), retinal abnormalities (37%) and developmental delay (8%). We found an inverse correlation between repeat size and disease severity, similar to adult-onset FSHD. De novo FSHD1 mutations were more prevalent than in adult-onset FSHD. Compared to adult FSHD, our findings indicate that early onset FSHD is overall characterized by a more severe muscle phenotype and a higher prevalence of systemic features. However, similar as in adults, a significant clinical heterogeneity was observed. Based on this, we consider early onset FSHD to be on the severe end of the FSHD disease spectrum. We found natural history studies and treatment studies to be very scarce in early onset FSHD, therefore longitudinal studies are needed to improve prognostication, clinical management and trial-readiness. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Comparative gene expression profiling of placentas from patients with severe pre-eclampsia and unexplained fetal growth restriction

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    Kurahashi Hiroki

    2011-08-01

    Full Text Available Abstract Background It has been well documented that pre-eclampsia and unexplained fetal growth restriction (FGR have a common etiological background, but little is known about their linkage at the molecular level. The aim of this study was to further investigate the mechanisms underlying pre-eclampsia and unexplained FGR. Methods We analyzed differentially expressed genes in placental tissue from severe pre-eclamptic pregnancies (n = 8 and normotensive pregnancies with or (n = 8 without FGR (n = 8 using a microarray method. Results A subset of the FGR samples showed a high correlation coefficient overall in the microarray data from the pre-eclampsia samples. Many genes that are known to be up-regulated in pre-eclampsia are also up-regulated in FGR, including the anti-angiogenic factors, FLT1 and ENG, believed to be associated with the onset of maternal symptoms of pre-eclampsia. A total of 62 genes were found to be differentially expressed in both disorders. However, gene set enrichment analysis for these differentially expressed genes further revealed higher expression of TP53-downstream genes in pre-eclampsia compared with FGR. TP53-downstream apoptosis-related genes, such as BCL6 and BAX, were found to be significantly more up-regulated in pre-eclampsia than in FGR, although the caspases are expressed at equivalent levels. Conclusions Our current data indicate a common pathophysiology for FGR and pre-eclampsia, leading to an up-regulation of placental anti-angiogenic factors. However, our findings also suggest that it may possibly be the excretion of these factors into the maternal circulation through the TP53-mediated early-stage apoptosis of trophoblasts that leads to the maternal symptoms of pre-eclampsia.

  1. Tourette syndrome and comorbid early-onset schizophrenia.

    Science.gov (United States)

    Kerbeshian, Jacob; Peng, Chun-Zi; Burd, Larry

    2009-12-01

    A study of the shared phenomenology between Tourette syndrome (TS) and schizophrenia. An illustrative case report is presented. We used a chart review of 399 clinically ascertained patients with TS to identify 10 cases meeting criteria for schizophrenia. From our 10 patients, salient clinical characteristics were then tabulated. We then extracted similar clinical characteristics from a previously published series of patients with comorbid TS and schizophrenia in order to combine cases and allow for a comparison between childhood-onset schizophrenia (COS), adolescent-onset schizophrenia (AdolOS), and adult-onset schizophrenia (AduOS) cases in these groups. We found 10 cases of schizophrenia (all were males) in the 399 TS patients for a prevalence rate of 2.5% (95% CI 0.96-4.04). Mean age of tic onset for TS diagnostic criteria ranged from 2-14 years with a mean of 8.2 years. The mean age of diagnosis for schizophrenia was 14.2 (range 9-23 years). We found six cases of schizophrenia with onset of positive psychotic symptoms by 13 years of age, two cases with onset after 13 years of age and before 18 years of age, and two cases with onset after 18 years of age. Attention deficit hyperactivity disorder was present at a higher rate (70%) than one would expect in a clinically ascertained group of patients with TS. Comparison between COS, AdolOS and AduOS in our pooled cases noted a sex bias skewed toward males. Catatonic symptoms may be more likely in child or adolescent onset cases and negative symptoms more likely in AduOS cases. The 2.5% prevalence of schizophrenia in our TS sample exceeds the 1% expected rate of schizophrenia in the general population (chi-square=9.14; P=.0025). The six cases of COS (before 13 years of age) exceeds the expected rate of 1-2 per 100,000 (chi-square=4499; P=.0001). The 752-fold increase in observed rates of comorbid TS and COS over expected rates suggests a role for unknown common underlying etiologic factors. Based on clinical features

  2. Early-onset obsessive-compulsive disorder and personality disorders in adulthood.

    Science.gov (United States)

    Maina, Giuseppe; Albert, Umberto; Salvi, Virginio; Pessina, Enrico; Bogetto, Filippo

    2008-03-15

    Obsessive-compulsive disorder (OCD) often emerges in childhood or adolescence. The aim of the present study was to evaluate whether adult patients with prepuberal onset differ from subjects with later onset in terms of personality disorder comorbidity. The Structured Clinical Interview for DSM-IV Axis II Disorders was used to assess 148 patients with a principal diagnosis of OCD according to the Structured Clinical Interview for DSM-IV Axis I Disorders. The following two subgroups of subjects were selected according to the age at onset of symptomatology: patients with an early-onset ( or =17 years). Of the 148 patients screened for the present study, 33 (22.3%) had an early onset and 1369 (46.6%) had a later onset. With regard to personality disorders, early-onset patients showed more OC personality disorders (OCPD) than later onset patients. Our finding suggests that OCD in childhood increases the risk for developing OCPD in adulthood, or that early-onset OCD and OCPD share a common pathogenesis.

  3. Social Anxiety and Onset of Drinking in Early Adolescence

    Science.gov (United States)

    Tomlinson, Kristin L.; Cummins, Kevin M.; Brown, Sandra A.

    2013-01-01

    The present study examines several types of social anxiety that may be associated with the onset of alcohol use in middle school students, and whether the relationship differs by sex and grade. Students in the seventh and eighth grades (N = 2,621) completed the Social Anxiety Scale for Adolescents and a measure of lifetime drinking via schoolwide…

  4. Early Onset Optic Neuritis Following Measles-Rubella Vaccination

    Directory of Open Access Journals (Sweden)

    Siamak Moradian

    2008-12-01

    Full Text Available

    PURPOSE: To report two cases of optic neuritis with onset less than 24 hours following measles-rubella (MR vaccination. CASE REPORT: Two teenage patients developed acute optic neuritis 6 to 7 hours after MR booster vaccination. The first patient demonstrated bilateral papillitis and severe visual loss but improved significantly with pulse intravenous steroid therapy with methylprednisolone 500 mg/day. The second patient had unilateral retrobulbar optic neuritis and demonstrated excellent visual recovery without intervention. CONCLUSION: Acute optic neuritis is a rare complication of MR vaccination and may occur early after immunization.

  1. A case of early-onset radiation retinopathy

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Yoko; Den, Seika; Shimizu, Kazuhiro; Ikeda, Tsunehiko [Osaka Medical Coll., Takatsuki (Japan)

    2001-12-01

    We encountered a 27-year-old male early caused by radiation retinopathy five months after radiotherapy (51 Gy) for astrocytoma. The retinopathy was the proliferative retinopathy, with several dot and blot hemorrhages, hard and soft exudate, increased capillary permeability, macula edema and avasucular areas. So it was treated with panretial photocoagulation like diabetic retinopathy. Now hemorrhage, exudate, edema and avascular areas were improved. Photocoagulation treatment is effective to stop the progression of radiation retinopathy. Radiation retinopathy is sometimes early caused, therefore long-term follow up is recommended on starting radiotherapy. (author)

  2. A brief overview of preeclampsia.

    Science.gov (United States)

    Al-Jameil, Noura; Aziz Khan, Farah; Fareed Khan, Mohammad; Tabassum, Hajera

    2014-02-01

    Preeclampsia (PE) is a leading cause of maternal mortality and morbidity worldwide. It occurs in women with first or multiple pregnancies and is characterized by new onset hypertension and proteinuria. Improper placentation is mainly responsible for the disease. If PE remains untreated, it moves towards more serious condition known as eclampsia. Hypertension, diabetes mellitus, proteinuria, obesity, family history, nulliparity, multiple pregnancies and thrombotic vascular disease contribute as the risk factors for PE. PE triggered metabolic stress causes vascular injury, thus contributing to the development of cardiovascular disease (CVD) and/or chronic kidney disease (CKD) in future. This risk appears to be increased especially in women with a history of recurrent PE and eclampsia. Clinically increased serum levels of sFlt-1 and decreased placental growth factor (PIGF) and vascular endothelial growth factor (VEGF) represent the severe condition of PE. The clinical findings of sever PE are assorted by the presence of systemic endothelial dysfunction, microangiopathy, the liver (hemolysis, elevated liver function tests and low platelet count, namely HELLP syndrome) and the kidney (proteinuria). The early detection of PE is one of the most important goals in obstetrics.

  3. Risk Factors for Early-Onset Peritonitis in Southern Chinese Peritoneal Dialysis Patients.

    Science.gov (United States)

    Wu, Haishan; Huang, Rong; Yi, Chunyan; Wu, Juan; Guo, Qunying; Zhou, Qian; Yu, Xueqing; Yang, Xiao

    ♦ BACKGROUND: Early peritonitis was confirmed to be associated with a higher risk of early technique failure. However, literature concerning peritonitis within the first 3 months of peritoneal dialysis (PD) initiation is scarce. The present study was to investigate risk factors associated with early-onset peritonitis in PD patients. ♦ METHODS: In this retrospective observational cohort study, all incident PD patients from January 1, 2006, to December 31, 2013, were recruited and followed up until December 31, 2014. According to time-to-first episode of peritonitis, patients were divided into early-onset (≤ 3 months) peritonitis and late-onset (> 3 months) peritonitis. Baseline demographic, clinical, and laboratory data, as well as episodes of peritonitis, were collected. Risk factors associated with early-onset peritonitis were evaluated using logistic regression model. ♦ RESULTS: Of 1,690 patients on PD, 503 (29.8%) developed at least 1 episode of peritonitis and 118 (7.0%) patients presented the first episodes of peritonitis within the first 3 months. A multivariate logistic analysis showed that higher body mass index (BMI) (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.01 - 1.15, p = 0.034), hypoalbuminemia (OR 1.75, 95% CI 1.11 - 2.78, p = 0.017), and catheter exit-site infection (OR 4.14, 95% CI 2.45 - 7.00, p peritonitis. Compared to those with late-onset, patients with early-onset peritonitis had a higher overall peritonitis rate (0.76 vs 0.38 per patient-year, p 0.05). ♦ CONCLUSIONS: Higher BMI, hypoalbuminemia, and catheter exit-site infection were the risk factors associated with early-onset peritonitis in PD patients. Copyright © 2016 International Society for Peritoneal Dialysis.

  4. Highly significant association between two common single nucleotide polymorphisms in CORIN gene and preeclampsia in Caucasian women.

    Directory of Open Access Journals (Sweden)

    Alain Stepanian

    Full Text Available Preeclampsia is a frequent medical complication during pregnancy. Corin, a serine protease which activates pro-atrial natriuretic peptide, has recently been shown to be involved in the pathophysiology of preeclampsia. The aim of this study was to search for CORIN gene variations and their association to preeclampsia in Caucasian and African women. Our study population was composed of 571 pregnant women (295 with preeclampsia and 276 normotensive controls matched for maternal and gestational age, and ethnic origin. The 22 exons of the CORIN gene were sequenced in a discovery sample (n = 260, where 31 single nucleotide polymorphisms were identified. In a replication sample (n = 311, 4 single nucleotide polymorphisms were tested. Two minor alleles (C for rs2271036 and G for rs2271037 were significantly associated to preeclampsia. Adjusted odds ratios [95% confidence interval] were 2.5 [1.2-3.8] (p = 0.007 and 2.3 [1.5-3.5] (p = 1.3 × 10(-4, respectively. These associations were ethnic-specific, as only found in the Caucasian of subjects (odds ratio = 3.5 [1.8-6.6], p = 1.1 × 10(-4; odds ratio = 3.1 [1.7-5.8], p = 2.1 × 10(-4, for each single nucleotide polymorphism, respectively. The two single nucleotide polymorphisms are in almost perfect linkage disequilibrium (r(2 = 0.93. No specific association was found with severe preeclampsia, early-onset preeclampsia nor fetal growth retardation. In conclusion, this is the first report of a highly significant association between these two single nucleotide polymorphisms in CORIN gene and preeclampsia. Our findings further support the probability of a critical role of corin in preeclamspia pathophysiology at the uteroplacental interface.

  5. Preliminary findings demonstrating latent effects of early adolescent marijuana use onset on cortical architecture

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    Francesca M. Filbey

    2015-12-01

    Conclusions: Divergent patterns between current MJ use and elements of cortical architecture were associated with early MJ use onset. Considering brain development in early adolescence, findings are consistent with disruptions in pruning. However, divergence with continued use for many years thereafter suggests altered trajectories of brain maturation during late adolescence and beyond.

  6. Early Onset Substance Use in Adolescents with Depressive, Conduct, and Comorbid Symptoms

    Science.gov (United States)

    Stone, Andrea L.; Vander Stoep, Ann; McCauley, Elizabeth

    2016-01-01

    This study investigates whether co-occurring depressive and conduct symptoms in early adolescence are associated with an elevated occurrence of early onset substance. Five hundred twenty-one sixth graders were assessed for depressive symptoms and conduct problems and underwent five substance use assessments during middle school. Logistic…

  7. Preeclampsia: from epidemiological observations to molecular mechanisms

    Directory of Open Access Journals (Sweden)

    P. López-Jaramillo

    2001-10-01

    Full Text Available Preeclampsia is the main cause of maternal mortality and is associated with a five-fold increase in perinatal mortality in developing countries. In spite of this, the etiology of preeclampsia is unknown. The present article analyzes the contradictory results of the use of calcium supplementation in the prevention of preeclampsia, and tries to give an explanation of these results. The proposal of an integrative model to explain the clinical manifestations of preeclampsia is discussed. In this proposal we suggest that preeclampsia is caused by nutritional, environmental and genetic factors that lead to the creation of an imbalance between the free radicals nitric oxide, superoxide and peroxynitrate in the vascular endothelium. The adequate interpretation of this model would allow us to understand that the best way of preventing preeclampsia is the establishment of an adequate prenatal control system involving adequate antioxidant vitamin and mineral supplementation, adequate diagnosis and early treatment of asymptomatic urinary and vaginal infections. The role of infection in the genesis of preeclampsia needs to be studied in depth because it may involve a fundamental change in the prevention and treatment of preeclampsia.

  8. Late- versus early-onset geriatric depression in a memory research center

    Directory of Open Access Journals (Sweden)

    Carol Dillon

    2009-10-01

    Full Text Available Carol Dillon1, Ricardo F Allegri2, Cecilia M Serrano1, Mónica Iturry1, Pablo Salgado1, Frank B Glaser1, Fernando E Taragano21Memory Research Center, Department of Neurology, Hospital General Abel Zubizarreta, GCBA Buenos Aires, Argentina; 2Department of Neuropsychology (SIREN, CEMIC University, Buenos Aires, ArgentinaObjective: To contrast early-onset (<60 years and late-onset (>60 years depression in geriatric patients by evaluating differences in cognition, vascular comorbidity and sociological risk factors. Both patient groups were compared with normal subjects.Materials and methods: We recruited 76 patients with depressive symptoms (37 late onset and 39 early onset and 17 normal controls matched by age and educational level. All subjects were assessed using a semistructured neuropsychiatric interview and an extensive neuropsychological battery. Vascular and sociological risk factors were also evaluated.Results: We found a significant variation in performance between depressive patients and normal controls in most cognitive functions, especially memory (P < 0.0001, semantic fluency (P < 0.0001, verbal fluency, and digit-symbol (P < 0.0001. Late-onset depression patients scored lower and exhibited more severe impairment in memory domains than early-onset depression patients (P < 0.05. Cholesterol levels and marital status were significantly (P < 0.05 different between the depressive groups. Both depressed groups (early- and lateonset were more inactive than controls (P < 0.05; odds ratio: 6.02.Conclusion: Geriatric depression may be a manifestation of brain degeneration, and the initial symptom of a dementia. It is important to consider this in the treatment of patients that exhibit late-onset depressive symptoms.Keywords: early- and late-onset depression, geriatrics, cognition

  9. Common variants at five new loci associated with early-onset inflammatory bowel disease.

    Science.gov (United States)

    Imielinski, Marcin; Baldassano, Robert N; Griffiths, Anne; Russell, Richard K; Annese, Vito; Dubinsky, Marla; Kugathasan, Subra; Bradfield, Jonathan P; Walters, Thomas D; Sleiman, Patrick; Kim, Cecilia E; Muise, Aleixo; Wang, Kai; Glessner, Joseph T; Saeed, Shehzad; Zhang, Haitao; Frackelton, Edward C; Hou, Cuiping; Flory, James H; Otieno, George; Chiavacci, Rosetta M; Grundmeier, Robert; Castro, Massimo; Latiano, Anna; Dallapiccola, Bruno; Stempak, Joanne; Abrams, Debra J; Taylor, Kent; McGovern, Dermot; Silber, Gary; Wrobel, Iwona; Quiros, Antonio; Barrett, Jeffrey C; Hansoul, Sarah; Nicolae, Dan L; Cho, Judy H; Duerr, Richard H; Rioux, John D; Brant, Steven R; Silverberg, Mark S; Taylor, Kent D; Barmuda, M Michael; Bitton, Alain; Dassopoulos, Themistocles; Datta, Lisa Wu; Green, Todd; Griffiths, Anne M; Kistner, Emily O; Murtha, Michael T; Regueiro, Miguel D; Rotter, Jerome I; Schumm, L Philip; Steinhart, A Hillary; Targan, Stephen R; Xavier, Ramnik J; Libioulle, Cécile; Sandor, Cynthia; Lathrop, Mark; Belaiche, Jacques; Dewit, Olivier; Gut, Ivo; Heath, Simon; Laukens, Debby; Mni, Myriam; Rutgeerts, Paul; Van Gossum, André; Zelenika, Diana; Franchimont, Denis; Hugot, J P; de Vos, Martine; Vermeire, Severine; Louis, Edouard; Cardon, Lon R; Anderson, Carl A; Drummond, Hazel; Nimmo, Elaine; Ahmad, Tariq; Prescott, Natalie J; Onnie, Clive M; Fisher, Sheila A; Marchini, Jonathan; Ghori, Jilur; Bumpstead, Suzannah; Gwillam, Rhian; Tremelling, Mark; Delukas, Panos; Mansfield, John; Jewell, Derek; Satsangi, Jack; Mathew, Christopher G; Parkes, Miles; Georges, Michel; Daly, Mark J; Heyman, Melvin B; Ferry, George D; Kirschner, Barbara; Lee, Jessica; Essers, Jonah; Grand, Richard; Stephens, Michael; Levine, Arie; Piccoli, David; Van Limbergen, John; Cucchiara, Salvatore; Monos, Dimitri S; Guthery, Stephen L; Denson, Lee; Wilson, David C; Grant, Straun F A; Daly, Mark; Silverberg, Mark S; Satsangi, Jack; Hakonarson, Hakon

    2009-12-01

    The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis are common causes of morbidity in children and young adults in the western world. Here we report the results of a genome-wide association study in early-onset IBD involving 3,426 affected individuals and 11,963 genetically matched controls recruited through international collaborations in Europe and North America, thereby extending the results from a previous study of 1,011 individuals with early-onset IBD. We have identified five new regions associated with early-onset IBD susceptibility, including 16p11 near the cytokine gene IL27 (rs8049439, P = 2.41 x 10(-9)), 22q12 (rs2412973, P = 1.55 x 10(-9)), 10q22 (rs1250550, P = 5.63 x 10(-9)), 2q37 (rs4676410, P = 3.64 x 10(-8)) and 19q13.11 (rs10500264, P = 4.26 x 10(-10)). Our scan also detected associations at 23 of 32 loci previously implicated in adult-onset Crohn's disease and at 8 of 17 loci implicated in adult-onset ulcerative colitis, highlighting the close pathogenetic relationship between early- and adult-onset IBD.

  10. Early-Onset Chronic Inflammatory Disease Associated with Maternal Microchimerism

    Directory of Open Access Journals (Sweden)

    Tomoaki Ishikawa

    2012-01-01

    Full Text Available Maternal microchimerism (mMc refers to the presence of a small population of cells originating from the mother. Whether mMc leads to autoimmune responses in children remains controversial. We describe here an 11-year-old boy with persistent fever and elevated levels of C-reactive protein from infancy onward. During infancy, the patient presented with high fever, skin rashes, and hepatic dysfunction. Careful examination including a liver biopsy failed to reveal the cause. At 4 years old, petechiae developed associated with thrombocytopenia and positive anti-dsDNA autoantibodies. Steroid pulse therapy was effective, but the effect of low-dose prednisone was insufficient. At age 9, an extensive differential diagnosis was considered especially for infantile onset autoinflammatory disorders but failed to make a definitive diagnosis. On admission, the patient exhibited short stature, hepatosplenomegaly, generalized superficial lymphadenopathy, and rashes. Laboratory findings revealed anemia, elevated levels of inflammation markers, and hypergammaglobulinemia. Serum complement levels were normal. Serum levels of IL-6 and B-cell activating factor were elevated. Viral infections were not identified. Although HLA typing revealed no noninherited maternal antigens in lymphocytes, female cells were demonstrated in the patient’s skin and lymph nodes, suggesting that maternal microchimerism might be involved in the pathogenesis of fever without source in infants.

  11. A prospective observational study of early fetal growth velocity and its association with birth weight, gestational age at delivery, preeclampsia, and perinatal mortality

    Energy Technology Data Exchange (ETDEWEB)

    Vasudeva, Akhila, E-mail: akhilavasudeva@gmail.com [Department of Obstetrics and Gynaecology, Kasturba Medical College, Manipal University, Manipal 576104, Karnataka State (India); Abraham, Anu Annie, E-mail: anuannieabraham@yahoo.com [Department of Obstetrics and Gynaecology, Kasturba Medical College, Manipal University, Manipal 576104, Karnataka State (India); Kamath, Asha, E-mail: aashakamat@gmail.com [Department of Community Medicine, Kasturba Medical College, Manipal, A Constituent College of Manipal University (India)

    2013-08-15

    Objectives: We aimed to measure early fetal growth velocity and to correlate this with the birth weight, gestational age at delivery, and with the incidence of adverse pregnancy outcomes specifically preeclampsia and perinatal mortality. Methods: A data based prospective observational study, wherein sonographic biometry data and specific pregnancy outcome related data were collected from pregnant women's records, starting soon after their first antenatal visit. Early fetal growth velocity was measured using BPD growth between 11 and 14 weeks scan and anomaly scan and standardizing this by Z scoring. Results: Out of 607 fetuses, 41 (6.7%) were slow growing, 531 (87.4%) normally growing, and 35 (5.7%) fast growing (Z scoring <10th{sup ,} 10–90th, and >90th percentiles respectively). As fetal growth velocity increased, the mean birth weight decreased from 2958.7 ± 388.9 (<10th centile), 2742.1 ± 576.6 (10–90th centile), to 2339.3 ± 729.4 (>90th centile); and gestational age at delivery decreased from 38.5 ± 1.3 (<10th centile), 37.5 ± 2.1 (10–90th centile), to 36.4 ± 2.2 (>90th centile), and both these trends were statistically significant (p < 0.001).Faster growing fetuses had a higher risk of preterm delivery(spontaneous + indicated) compared to other 2 groups [OR 4.42 (2.18,8.98)], and slower growing fetuses had a higher risk of postdated deliveries compared to other 2 groups [OR 3.042 (1.44, 6.45)].We found no significant association between early fetal growth velocity and incidence of small for gestational age at birth/low birth weight at term, preeclampsia, and perinatal mortality. Conclusions: Early fetal growth velocity between first and second trimesters, may be one of the important factors influencing ultimate birthweight and gestational age at delivery.

  12. A prospective observational study of early fetal growth velocity and its association with birth weight, gestational age at delivery, preeclampsia, and perinatal mortality

    International Nuclear Information System (INIS)

    Vasudeva, Akhila; Abraham, Anu Annie; Kamath, Asha

    2013-01-01

    Objectives: We aimed to measure early fetal growth velocity and to correlate this with the birth weight, gestational age at delivery, and with the incidence of adverse pregnancy outcomes specifically preeclampsia and perinatal mortality. Methods: A data based prospective observational study, wherein sonographic biometry data and specific pregnancy outcome related data were collected from pregnant women's records, starting soon after their first antenatal visit. Early fetal growth velocity was measured using BPD growth between 11 and 14 weeks scan and anomaly scan and standardizing this by Z scoring. Results: Out of 607 fetuses, 41 (6.7%) were slow growing, 531 (87.4%) normally growing, and 35 (5.7%) fast growing (Z scoring <10th , 10–90th, and >90th percentiles respectively). As fetal growth velocity increased, the mean birth weight decreased from 2958.7 ± 388.9 (<10th centile), 2742.1 ± 576.6 (10–90th centile), to 2339.3 ± 729.4 (>90th centile); and gestational age at delivery decreased from 38.5 ± 1.3 (<10th centile), 37.5 ± 2.1 (10–90th centile), to 36.4 ± 2.2 (>90th centile), and both these trends were statistically significant (p < 0.001).Faster growing fetuses had a higher risk of preterm delivery(spontaneous + indicated) compared to other 2 groups [OR 4.42 (2.18,8.98)], and slower growing fetuses had a higher risk of postdated deliveries compared to other 2 groups [OR 3.042 (1.44, 6.45)].We found no significant association between early fetal growth velocity and incidence of small for gestational age at birth/low birth weight at term, preeclampsia, and perinatal mortality. Conclusions: Early fetal growth velocity between first and second trimesters, may be one of the important factors influencing ultimate birthweight and gestational age at delivery

  13. Early Onset of Laying and Bumblefoot Favor Keel Bone Fractures

    Science.gov (United States)

    Gebhardt-Henrich, Sabine G.; Fröhlich, Ernst K. F.

    2015-01-01

    Simple Summary Numerous studies have documented a high prevalence of keel bone fractures in laying hens. In this longitudinal study, 80 white and brown laying hens were regularly checked for keel bone deviations and fractures while egg production was individually monitored. About 62% of the hens had broken keel bones at depopulation. More new fractures occurred during the time when laying rates were highest. Hens with broken keel bones at depopulation had laid their first egg earlier than hens with intact keel bones. All birds with bumblefoot on both feet had a fracture at depopulation. Abstract Numerous studies have demonstrated influences of hybrid, feed, and housing on prevalence of keel bone fractures, but influences of behavior and production on an individual level are less known. In this longitudinal study, 80 white and brown laying hens were regularly checked for keel bone deviations and fractures while egg production was individually monitored using Radio Frequency Identification (RFID) from production until depopulation at 65 weeks of age. These focal birds were kept in eight pens with 20 hens per pen in total. About 62% of the hens had broken keel bones at depopulation. The occurrence of new fractures was temporally linked to egg laying: more new fractures occurred during the time when laying rates were highest. Hens with fractured keel bones at depopulation had laid their first egg earlier than hens with intact keel bones. However, the total number of eggs was neither correlated with the onset of egg laying nor with keel bone fractures. All birds with bumblefoot on both feet had a fracture at depopulation. Hens stayed in the nest for a longer time during egg laying during the ten days after the fracture than during the ten days before the fracture. In conclusion, a relationship between laying rates and keel bone fractures seems likely. PMID:26633520

  14. Differences in diagnostic subtypes among patients with late and early onset of a single depressive episode

    DEFF Research Database (Denmark)

    Kessing, Lars Vedel

    2006-01-01

    OBJECTIVE: It is unclear whether patients with late onset and patients with early onset present with different subtypes of depression. The aim of the study was to compare the prevalence of subtypes of ICD-10 single depressive episodes for patients with late onset (age >65 years) and patient...... with early onset (age single depressive episode in a period from 1994-2002 at the end of the first outpatient treatment or at the first discharge from...... psychiatric hospitalisation ever in Denmark were identified in a nationwide register. RESULTS: In total, 18.192 patients were given a diagnosis of a single depressive episode at the first outpatient contact and 8.396 patients were given a diagnosis of a single depressive episode at the first psychiatric...

  15. Is an Early Age at Illness Onset in Schizophrenia Associated With Increased Genetic Susceptibility?

    DEFF Research Database (Denmark)

    Hilker, Rikke; Helenius, Dorte; Fagerlund, Birgitte

    2017-01-01

    with schizophrenia spectrum) and a subsample of N = 448 (affected with schizophrenia). Survival analysis was applied to investigate the effect of age at illness onset. Findings We found that early age at illness onset compared to later onset in the first diagnosed twin can be considered a major risk factor......Background Early age at illness onset has been viewed as an important liability marker for schizophrenia, which may be associated with an increased genetic vulnerability. A twin approach can be valuable, because it allows for the investigation of specific illness markers in individuals...... with a shared genetic background. Methods We linked nationwide registers to identify a cohort of twin pairs born in Denmark from 1951 to 2000 (N = 31,524 pairs), where one or both twins had a diagnosis in the schizophrenia spectrum. We defined two groups consisting of; N = 788 twin pairs (affected...

  16. Depression and quality of life in monogenic compared to idiopathic, early-onset Parkinson's disease

    DEFF Research Database (Denmark)

    Kasten, Meike; Kertelge, Lena; Tadic, Vera

    2012-01-01

    , and 44% of manifesting carriers of mutations in PD genes, but was rare in the nonmanifesting carriers (7%) and healthy controls (5%). Subjects with Parkinson-associated depression reported fewer feelings of guilt or self-doubt than treated controls, but the occurrence of suicidal ideation was associated......Quality of life (QoL) is decreased in PD and is linked with depression and anxiety. However, little is known about QoL in monogenic PD. Subjects with mutations in PD genes were recruited from ongoing family and genetic studies (manifesting carriers, n = 23; nonmanifesting carriers, n = 19......). For comparison purposes, we included patients with idiopathic PD (IPD; n = 128; early onset, n = 38; late onset, n = 90), healthy controls (n = 127), and data on depressive symptoms of 144 patients with major depression (treated controls). Depression affected 31% of early-onset PD cases, 21% of late-onset cases...

  17. The Use of Cannabis as a Predictor of Early Onset of Bipolar Disorder and Suicide Attempts

    Directory of Open Access Journals (Sweden)

    Rafaela Torres Portugal Leite

    2015-01-01

    Full Text Available Introduction. Bipolar disorder (BD implies risk of suicide. The age at onset (AAO of BD carries prognostic significance. Substance abuse may precede the onset of BD and cannabis is the most common illicit drug used. The main goal of this study is to review the association of cannabis use as a risk factor for early onset of BD and for suicide attempts. Materials and Methods. PubMed database was searched for articles using key words “bipolar disorder,” “suicide attempts,” “cannabis,” “marijuana,” “early age at onset,” and “early onset.” Results. The following percentages in bipolar patients were found: suicide attempts 3.6–42%; suicide attempts and substance use 5–60%; suicide attempts and cannabis use 15–42%. An early AAO was associated with cannabis misuse. The mean age of the first manic episode in individuals with and without BD and cannabis use disorder (CUD was 19.5 and 25.1 years, respectively. The first depressive episode was at 18.5 and 24.4 years, respectively. Individuals misusing cannabis showed increased risk of suicide. Discussion. Cannabis use is associated with increased risk of suicide attempts and with early AAO. However, the effect of cannabis at the AAO and suicide attempts is not clear.

  18. Genome-wide association scan for variants associated with early-onset prostate cancer.

    Directory of Open Access Journals (Sweden)

    Ethan M Lange

    Full Text Available Prostate cancer is the most common non-skin cancer and the second leading cause of cancer related mortality for men in the United States. There is strong empirical and epidemiological evidence supporting a stronger role of genetics in early-onset prostate cancer. We performed a genome-wide association scan for early-onset prostate cancer. Novel aspects of this study include the focus on early-onset disease (defined as men with prostate cancer diagnosed before age 56 years and use of publically available control genotype data from previous genome-wide association studies. We found genome-wide significant (p<5×10(-8 evidence for variants at 8q24 and 11p15 and strong supportive evidence for a number of previously reported loci. We found little evidence for individual or systematic inflated association findings resulting from using public controls, demonstrating the utility of using public control data in large-scale genetic association studies of common variants. Taken together, these results demonstrate the importance of established common genetic variants for early-onset prostate cancer and the power of including early-onset prostate cancer cases in genetic association studies.

  19. Key goals and indicators for successful aging of adults with early-onset disability.

    Science.gov (United States)

    LaPlante, Mitchell P

    2014-01-01

    Substantial improvements have occurred in the longevity of several groups of individuals with early-onset disabilities, with many now surviving to advanced ages. This paper estimates the population of adults aging with early-onset disabilities at 12-15 million persons. Key goals for the successful aging of adults with early-onset disabilities are discussed, emphasizing reduction in risks for aging-related chronic disease and secondary conditions, while promoting social participation and independence. However, indicators suggest that elevated risk factors for aging-related chronic diseases, including smoking, obesity, and inactivity, as well as barriers to prevention and the diminished social and economic situation of adults with disabilities are continuing impediments to successful aging that must be addressed. Increased provider awareness that people with early-onset disabilities are aging and can age successfully and the integration of disability and aging services systems are transformative steps that will help adults with early-onset disability to age more successfully. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Radiation induced early onset of neuro-cognitive changes

    International Nuclear Information System (INIS)

    Kumar, Mayank; Haridas, Seenu; Gupta, Mamta; Trivedi, Richa; Khushu, Subhash; Manda, Kailash

    2012-01-01

    Exposure to ionizing radiations has been shown to cause many detrimental effects. Primarily, the effects observed are broadly classified into hematopoietic syndrome at lower doses, gastrointestinal syndrome and central nervous system dysfunctions at high doses. However, recent studies reported that even at lower doses, there is an effect seen on the nervous system which can be observed as a decline in cognitive abilities. This has been reported in patients undergoing radiotherapy. The cognitive decline, especially in young patients affects development and has been shown to persist for years after the therapy. Thus, the aim of this study was to study and consolidate the early effects of radiation exposure which result in behavioural alterations and cognitive decline. Since, radiation-induced early changes in behavioural functions are poorly understood, therefore, the present investigation aimed to conceptualize and design behavioural test batteries in order to systematically study the immediate alterations in behavioural function following irradiation with a-rays. The behavioural alterations were correlated to changes in the different area of brain like hippocampus, thalamus, hypothalamus and corpus callosum using Diffusion Tensor Imaging (DTI) studies. Present study reported profound changes in behaviour, as well as alterations in the morphology of the brain tissue as perceived by DTI, 48 hours after exposure to ionizing radiations. These changes need to be correlated and clarified further to understand the mechanisms behind the cognitive dysfunctions occurring immediately after radiation exposure as well as to find out a therapeutic window to counteract or reduce the effect of long term cognitive changes following irradiation. (author)

  1. Cognitive Development in Infantile-Onset Pompe Disease Under Very Early Enzyme Replacement Therapy.

    Science.gov (United States)

    Lai, Chih-Jou; Hsu, Ting-Rong; Yang, Chia-Feng; Chen, Shyi-Jou; Chuang, Ya-Chin; Niu, Dau-Ming

    2016-12-01

    Most patients with infantile-onset Pompe disease die in early infancy before beginning enzyme replacement therapy, which has made it difficult to evaluate the impact of Pompe disease on cognitive development. Patients with infantile-onset Pompe disease can survive with enzyme replacement therapy, and physicians can evaluate cognitive development in these patients. We established an effective newborn screening program with quick clinical diagnostic criteria. Cognitive and motor development were evaluated using the Bayley Scales of Infant and Toddler Development-Third Edition at 6, 12, and 24 months of age. The patients who were treated very early demonstrate normal cognitive development with no significant change in cognition during this period (P = .18 > .05). The cognitive development was positively correlated with motor development (r = 0.533, P = .011). The results indicated that very early enzyme replacement therapy could protect cognitive development in patients with infantile-onset Pompe disease up to 24 months of age. © The Author(s) 2016.

  2. IKs Gain- and Loss-of-Function In Early-Onset Lone Atrial Fibrillation

    DEFF Research Database (Denmark)

    Steffensen, Annette Buur; Refsgaard, Lena; Andersen, Martin Nybo

    2015-01-01

    INTRODUCTION: Atrial fibrillation (AF) is the most frequent cardiac arrhythmia. The potassium current IKs is essential for cardiac repolarization. Gain-of-function mutation in KCNQ1, the gene encoding the pore-forming α-subunit of the IKs channel (KV 7.1), was the first ion channel dysfunction...... to be associated with familial AF. We hypothesized that early-onset lone AF is associated with a high prevalence of mutations in KCNQ1. METHODS AND RESULTS: We bidirectionally sequenced the entire coding sequence of KCNQ1 in 209 unrelated patients with early-onset lone AF (...-of-function phenotype. CONCLUSIONS: Mutations in the IKs channel leading to gain-of-function have previously been described in familial AF, yet this is the first time a loss-of-function mutation in KCNQ1 is associated with early-onset lone AF. These findings suggest that both gain-of function and loss...

  3. Association between Placental Lesions, Cytokines and Angiogenic Factors in Pregnant Women with Preeclampsia.

    Directory of Open Access Journals (Sweden)

    Ingrid C Weel

    Full Text Available Preeclampsia (PE is considered the leading cause of maternal and perinatal morbidity and mortality. The placenta seems to play an essential role in this disease, probably due to factors involved in its formation and development. The present study aimed to investigate the association between placental lesions, cytokines and angiogenic factors in pregnant women with preeclampsia (PE. We evaluated 20 normotensive pregnant women, 40 with early-onset PE and 80 with late-onset PE. Placental samples were analyzed for histopathology, immunohistochemistry and determination of granulocyte-macrophage colony-stimulating factor (GM-CSF, interleukin-10 (IL-10, transforming growth factor-beta 1 (TGF-β1, tumor necrosis factor-alpha (TNF-α, placental growth factor (PlGF, vascular endothelial growth factor (VEGF, fms-like tyrosine-kinase-1 (Flt-1 and endoglin (Eng levels. Higher percentages of increased syncytial knots and increased perivillous fibrin deposits, and greater levels of TNF-α, TGF-β1and Flt-1 were detected in placentas from early-onset PE. Levels of IL-10, VEGF and PlGF were decreased in PE versus normotensive placentas. Both the TNF-α/IL-10 and sFlt-1/PlGF ratios were higher in placental homogenate of early-onset PE than late-onset PE and control groups. The more severe lesions and the imbalance between TNF-α/IL-10 and PlGF/sFlt-1 in placentas from early-onset PE allows differentiation of early and late-onset PE and suggests higher placental impairment in early-onset PE.

  4. The role of selenium in predicting preeclampsia

    Directory of Open Access Journals (Sweden)

    Z Ghaemi

    2013-10-01

    Full Text Available Introduction: Preeclampsia is a common disorder that is a leading cause of perinatal and maternal morbidity and mortality; however its specific etiology has still remained obscure.The first step in preventing preeclampsia is early detection of women at risk. Since there is no valid and reliable screening test, appropriate diagnostic and screening tests are necessary, which are inexpensive, non-invasive and beneficial for pregnant women. Therefore, regarding the role of selenium as an antioxidant in the prevention preeclampsia, this study was designed which aimed to determine the prognostic value of plasma selenium levels in the diagnosis of preeclampsia in primigravida women Methods: In a nested case control design, a sample of 650 normal primigravida women of 24-28 weeks participated in the study. Subjects who involved the case group were followed up for 3 months and 38 were affected by preeclampsia. Blood samples were obtained from these 38patients as well as from 38 subjects as their matched controls. Moreover, the amount of selenium was measured by atomic absorption spectrometry. Results: The mean level of selenium in blood plasma of the cases was significantly lower than in their matched controls. The present study findings revealed that pregnant women with serum Se < 66.1 μg/L had a significantly increased risk of preeclampsia. Conclusion: Lower plasma selenium level in women destines to suffering from preeclampsia which confirms the destructive effect of selenium deficiency as an antioxidant in etiopathology of preeclampsia. Measurement of plasma selenium can improve the prediction of preeclampsia; thus, it seems that plasma selenium level test owns an acceptable sensitivity and specificity for predicting preeclampsia.

  5. An analysis on the roles of angiogenesis-related factors including serum vitamin D, soluble endoglin (sEng), soluble fms-like tyrosine kinase 1 (sFlt1), and vascular endothelial growth factor (VEGF) in the diagnosis and severity of late-onset preeclampsia.

    Science.gov (United States)

    Cim, Numan; Kurdoglu, Mertihan; Ege, Serhat; Yoruk, Ibrahim; Yaman, Gorkem; Yildizhan, Recep

    2017-07-01

    The aim of this study was to evaluate the roles of proangiogenic factors including serum vitamin D and vascular endothelial growth factor (VEGF) and anti-angiogenic factors including soluble endoglin (sEng) and soluble fms-like tyrosine kinase 1 (sFlt1) in the diagnosis and severity of late-onset preeclampsia. The study was conducted at Yuzuncu Yil University Research and Education Hospital Department of Gynecology and Obstetrics. The study included a patient group of 40 women with late-onset preeclampsia who were pregnant at ≥32 weeks of gestation according to the last menstrual period (LMP) or ultrasonographic fetal biometric measurement and a control group of 40 healthy pregnant women who presented to our clinic for routine pregnancy examination and were at the same age and gestational period with those in the patient group. The two groups were compared in terms of maternal age, gravida, parity, week of gestation, systolic/diastolic blood pressure, total protein in spot urine sample, 24-h urine protein, white blood cell (WBC), hemoglobin (Hgb), platelet count, urea, creatinine, liver function tests (AST, ALT, LDH), vitamin D 3 , 25(OH) vitamin D 3 , 1,25(OH) vitamin D 3 , sEng, sFlt1, and VEGF levels, mode of delivery, the infant APGAR score at 1 and 5 min after delivery, and infant weight at delivery. The groups were similar in terms of age, gravida, parity, week of gestation, serum vitamin D 3 , 25(OH) vitamin D 3 , 1,25(OH) 2 vitamin D 3 and VEGF levels, and infant weight at delivery (p > 0.05). Systolic/diastolic blood pressure, total protein in spot urine sample, 24-h urine protein, WBC, Hgb, serum urea, creatine, AST, ALT, and LDH were significantly higher in the preeclamptic group compared to the healthy group (p preeclampsia compared to the women with mild preeclampsia (p preeclampsia (p > 0.05). Both sEng and sFlt1 levels are remarkably high in patients with late-onset preeclampsia; however, only sEng may be a useful tool in the

  6. Loss of Nfkb1 leads to early onset aging.

    Science.gov (United States)

    Bernal, Giovanna M; Wahlstrom, Joshua S; Crawley, Clayton D; Cahill, Kirk E; Pytel, Peter; Liang, Hua; Kang, Shijun; Weichselbaum, Ralph R; Yamini, Bakhtiar

    2014-11-01

    NF-κB is a major regulator of age-dependent gene expression and the p50/NF-κB1 subunit is an integral modulator of NF-κB signaling. Here, we examined Nfkb1-/- mice to investigate the relationship between this subunit and aging. Although Nfkb1-/- mice appear similar to littermates at six months of age, by 12 months they have a higher incidence of several observable age-related phenotypes. In addition, aged Nfkb1-/- animals have increased kyphosis, decreased cortical bone, increased brain GFAP staining and a decrease in overall lifespan compared to Nfkb1+/+. In vitro, serially passaged primary Nfkb1-/- MEFs have more senescent cells than comparable Nfkb1+/+ MEFs. Also, Nfkb1-/- MEFs have greater amounts of phospho-H2AX foci and lower levels of spontaneous apoptosis than Nfkb1+/+, findings that are mirrored in the brains of Nfkb1-/- animals compared to Nfkb1+/+. Finally, in wildtype animals a substantial decrease in p50 DNA binding is seen in aged tissue compared to young. Together, these data show that loss of Nfkb1 leads to early animal aging that is associated with reduced apoptosis and increased cellular senescence. Moreover, loss of p50 DNA binding is a prominent feature of aged mice relative to young. These findings support the strong link between the NF-κB pathway and mammalian aging.

  7. Preeclampsia - self-care

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000606.htm Preeclampsia - self-care To use the sharing features on ... as you get used to it. Risks of Preeclampsia There are risks to both you and your ...

  8. Molecular Mechanisms of Preeclampsia

    Directory of Open Access Journals (Sweden)

    N. Vitoratos

    2012-01-01

    Full Text Available Preeclampsia is one of the leading causes of maternal morbidity/mortality. The pathogenesis of preeclampsia is still under investigation. The aim of this paper is to present the molecular mechanisms implicating in the pathway leading to preeclampsia.

  9. Spot urine protein measurements in normotensive pregnancies, pregnancies with isolated proteinuria and preeclampsia.

    Science.gov (United States)

    Kattah, Andrea; Milic, Natasa; White, Wendy; Garovic, Vesna

    2017-10-01

    We performed a prospective, longitudinal study of pregnant women presenting to their first obstetrics visits to characterize the changes in spot urine protein-to-creatinine (UPCR) and albumin-to-creatinine ratios (UACR) in normotensive pregnancies, as well as identify clinical characteristics associated with isolated proteinuria and preeclampsia. We measured spot urinary albumin, protein, and creatinine at the first prenatal visit, end of the second trimester, and at delivery. In the normotensive pregnancies ( n = 142), we found that from the beginning of pregnancy to delivery, UACR increased by a median [interquartile range (IQR)] of 14.7 mg/g Cr (3.74-51.8) and UPCR by 60 mg/g Cr (30-130) ( P 300 mg/g Cr in the absence of hypertension) was identified in 19/142 (13.4%) normotensive pregnancies. Increases in systolic and diastolic blood pressure from early pregnancy to delivery and increases in UACR from early to midpregnancy were associated with isolated proteinuria at delivery. Twelve women developed preeclampsia. Nulliparity, early, and midpregnancy diastolic blood pressures were strongly associated with the development of preeclampsia, but early changes in UACR were not. In conclusion, women who develop isolated proteinuria at delivery have a larger increase in blood pressure than women without proteinuria and have a "microalbuminuric" phase earlier in gestation, unlike women who develop preeclampsia. These findings suggest a different mechanism of urine protein excretion in women with isolated proteinuria as compared with women with preeclampsia, where proteinuria has a more abrupt onset. Copyright © 2017 the American Physiological Society.

  10. Association of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism with early-onset bipolar disorder.

    Science.gov (United States)

    Nassan, Malik; Croarkin, Paul E; Luby, Joan L; Veldic, Marin; Joshi, Paramjit T; McElroy, Susan L; Post, Robert M; Walkup, John T; Cercy, Kelly; Geske, Jennifer R; Wagner, Karen D; Cuellar-Barboza, Alfredo B; Casuto, Leah; Lavebratt, Catharina; Schalling, Martin; Jensen, Peter S; Biernacka, Joanna M; Frye, Mark A

    2015-09-01

    Brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) functional polymorphism has been implicated in early-onset bipolar disorder. However, results of studies are inconsistent. We aimed to further explore this association. DNA samples from the Treatment of Early Age Mania (TEAM) and Mayo Clinic Bipolar Disorder Biobank were investigated for association of rs6265 with early-onset bipolar disorder. Bipolar cases were classified as early onset if the first manic or depressive episode occurred at age ≤19 years (versus adult-onset cases at age >19 years). After quality control, 69 TEAM early-onset bipolar disorder cases, 725 Mayo Clinic bipolar disorder cases (including 189 early-onset cases), and 764 controls were included in the analysis of association, assessed with logistic regression assuming log-additive allele effects. Comparison of TEAM cases with controls suggested association of early-onset bipolar disorder with the rs6265 minor allele [odds ratio (OR) = 1.55, p = 0.04]. Although comparison of early-onset adult bipolar disorder cases from the Mayo Clinic versus controls was not statistically significant, the OR estimate indicated the same direction of effect (OR = 1.21, p = 0.19). When the early-onset TEAM and Mayo Clinic early-onset adult groups were combined and compared with the control group, the association of the minor allele rs6265 was statistically significant (OR = 1.30, p = 0.04). These preliminary analyses of a relatively small sample with early-onset bipolar disorder are suggestive that functional variation in BDNF is implicated in bipolar disorder risk and may have a more significant role in early-onset expression of the disorder. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. A neonate with intestinal volvulus without malrotation exhibiting early jaundice with a suspected fetal onset.

    Science.gov (United States)

    Hara, Kaori; Kinoshita, Mari; Kin, Takane; Arimitsu, Takeshi; Matsuzaki, Yohei; Ikeda, Kazushige; Tomita, Hiroshi; Fujino, Akihiro; Kuroda, Tatsuo

    2015-01-01

    Intestinal volvulus without malrotation is a rare disease that causes volvulus of the small intestine despite normal intestinal rotation and fixation. We encountered a neonate with this disease who developed early jaundice and was suspected to have a fetal onset. This patient was characterized by early jaundice complicating intestinal volvulus without malrotation and is considered to have exhibited reduced fetal movement and early jaundice as a result of volvulus, necrosis, and hemorrhage of the small intestine in the fetal period. If abdominal distention accompanied by early jaundice is noted in a neonate, intestinal volvulus without malrotation and associated intraabdominal hemorrhage should be suspected and promptly treated.

  12. First impression at stroke onset plays an important role in early hospital arrival.

    Science.gov (United States)

    Iguchi, Yasuyuki; Wada, Kuniyasu; Shibazaki, Kensaku; Inoue, Takeshi; Ueno, Yuji; Yamashita, Shinji; Kimura, Kazumi

    2006-01-01

    Treatment for acute ischemic stroke should be administered as soon as possible after symptom onset. The aim of this study was to investigate whether or not the patient's and bystander's first impression at stroke onset was associated with hospital arrival time. To investigate the factors influencing the prehospital delay, we prospectively interviewed consecutive stroke patients and bystanders about their first impression at the stroke onset and assessed the methods of transportation, and clinical characteristics. Early arrival was defined as a hospital arrival of within 2 h from stroke onset. One hundred thirty patients were enrolled: 82% were ischemic stroke and 18% were cerebral hemorrhage. The median interval between symptom onset and the hospital arrival was 7.5 h and 30% of patients presented within 2 h of stroke onset. First impression of stroke (odds ratios [OR] 4.56, 95% confidence interval [CI] 1.54-13.5, p=0.006), presence of consciousness disturbance (OR 4.29, CI 1.39-13.3, p=0.011), arrival through other facilities (OR 0.25, CI 0.08-0.76, p=0.015), a history of diabetes (OR 0.23, CI 0.06-0.80, p=0.028) and nocturnal onset (OR 0.19, CI 0.04-0.88, p=0.042) independently contributed to the early arrival. The first impression of patients and bystanders at stroke onset is important in order to reach hospital earlier in Japan. Public educational systems such as those, which advertise stroke warning signs, are necessary.

  13. Visual orientation in hospitalized boys with early onset conduct disorder and borderline intellectual functioning

    NARCIS (Netherlands)

    van der Meere, Jacob; Börger, Norbert; Pirila, Silja

    2012-01-01

    The aim of the present study is to investigate visual orientation in hospitalized boys with severe early onset conduct disorder and borderline intellectual functioning. It is tested whether boys with the dual diagnosis have a stronger action-oriented response style to visual-cued go signals than the

  14. Early onset of cannabis use: Does personality modify the relation with changes in perceived parental involvement?

    NARCIS (Netherlands)

    Creemers, H.E.; Buil, J.M.; Van Lier, P.A.C.; Keijsers, L.; Meeus, W.; Koot, H.M.; Huizink, A.C.

    2015-01-01

    Background: The present study examined (1) the association between changes in perceived parental control and support from age 13 to 15 and early onset of cannabis use (before age 16), and (2) whether personality modifies the association between a decline in perceived parental control and support and

  15. Mutations in MDH2, Encoding a Krebs Cycle Enzyme, Cause Early-Onset Severe Encephalopathy

    NARCIS (Netherlands)

    Ait-El-Mkadem, Samira; Dayem-Quere, Manal; Gusic, Mirjana; Chaussenot, Annabelle; Bannwarth, Sylvie; François, Bérengère; Genin, Emmanuelle C; Fragaki, Konstantina; Volker-Touw, Catharina L M; Vasnier, Christelle; Serre, Valérie; van Gassen, Koen L I; Lespinasse, Françoise; Richter, Susan; Eisenhofer, Graeme; Rouzier, Cécile; Mochel, Fanny; De Saint-Martin, Anne; Abi Warde, Marie-Thérèse; de Sain-van der Velden, Monique G M; Jans, Judith J M; Amiel, Jeanne; Avsec, Ziga; Mertes, Christian; Haack, Tobias B; Strom, Tim; Meitinger, Thomas; Bonnen, Penelope E; Taylor, Robert W; Gagneur, Julien; van Hasselt, Peter M; Rötig, Agnès; Delahodde, Agnès; Prokisch, Holger; Fuchs, Sabine A; Paquis-Flucklinger, Véronique

    2016-01-01

    MDH2 encodes mitochondrial malate dehydrogenase (MDH), which is essential for the conversion of malate to oxaloacetate as part of the proper functioning of the Krebs cycle. We report bi-allelic pathogenic mutations in MDH2 in three unrelated subjects presenting with early-onset generalized

  16. Deficient maturation of aspects of attention and executive functions in early onset schizophrenia

    DEFF Research Database (Denmark)

    Jepsen, Jens Richardt M; Fagerlund, Birgitte; Pagsberg, Anne Katrine

    2010-01-01

    The few existing long-term, neuropsychological follow-up studies of early onset schizophrenia (EOS) patients have reported relative stability in some cognitive functions but abnormal developmental trajectories in verbal memory, set shifting, aspects of attention, and speed of information processing...

  17. CD55 Deficiency, Early-Onset Protein-Losing Enteropathy, and Thrombosis

    NARCIS (Netherlands)

    Ozen, Ahmet; Comrie, William A; Ardy, Rico C; Domínguez Conde, Cecilia; Dalgic, Buket; Beser, Ömer F; Morawski, Aaron R; Karakoc-Aydiner, Elif; Tutar, Engin; Baris, Safa; Ozcay, Figen; Serwas, Nina K; Zhang, Yu; Matthews, Helen F; Pittaluga, Stefania; Folio, Les R; Unlusoy Aksu, Aysel; McElwee, Joshua J; Krolo, Ana; Kiykim, Ayca; Baris, Zeren; Gulsan, Meltem; Ogulur, Ismail; Snapper, Scott B; Houwen, Roderick H J; Leavis, Helen L; Ertem, Deniz; Kain, Renate; Sari, Sinan; Erkan, Tülay; Su, Helen C; Boztug, Kaan; Lenardo, Michael J

    2017-01-01

    BACKGROUND: Studies of monogenic gastrointestinal diseases have revealed molecular pathways critical to gut homeostasis and enabled the development of targeted therapies. METHODS: We studied 11 patients with abdominal pain and diarrhea caused by early-onset protein-losing enteropathy with primary

  18. Early onset of cannabis use: Does personality modify the relation with changes in perceived parental involvement?

    NARCIS (Netherlands)

    Creemers, Hanneke E.; Buil, J. Marieke; van Lier, Pot A. C.; Keijsers, Loes; Meeus, W.H.J.; Koot, Hans M.; Huizink, Anja C.

    2015-01-01

    Background The present study examined (1) the association between changes in perceived parental control and support from age 13 to 15 and early onset of cannabis use (before age 16), and (2) whether personality modifies the association between a decline in perceived parental control and support and

  19. The Rest-Activity Rhythm and Physical Activity in Early-Onset Dementia

    NARCIS (Netherlands)

    Hooghiemstra, A.M.; Eggermont, L.H.P.; Scheltens, P.; van der Flier, W.M.; Scherder, E.J.A.

    2015-01-01

    Background: A substantial part of elderly persons with dementia show rest-activity rhythm disturbances. The rest-activity rhythm is important to study in people with early-onset dementia (EOD) for rest-activity rhythm disturbances are predictive of institutionalization, and caregivers of young

  20. CDKL5 mutations in boys with severe encephalopathy and early-onset intractable epilepsy.

    Science.gov (United States)

    Elia, M; Falco, M; Ferri, R; Spalletta, A; Bottitta, M; Calabrese, G; Carotenuto, M; Musumeci, S A; Lo Giudice, M; Fichera, M

    2008-09-23

    To search for CDKL5 gene mutations in boys presenting with severe early-onset encephalopathy and intractable epilepsy, a clinical picture very similar to that already described in girls with CDKL5 mutations. Eight boys (age range 3-16 years, mean age 8.5 years, SD 4.38) with severe or profound mental retardation and early-onset intractable seizures were selected for CDKL5 gene mutation screening by denaturing high-performance liquid chromatography analysis. We found three unrelated boys carrying three different missense mutations of the CDKL5 gene: c.872G>A (p.C291Y), c.863C>T (p.T288I), and c.533G>C (p.R178P). They presented early-onset, polymorphous, and drug-resistant seizures, mostly myoclonic and tonic or spasms. EEG showed epileptiform abnormalities which were multifocal during wakefulness, and pseudoperiodic bisynchronous during sleep. This study describes three boys carrying CDKL5 missense mutations and their detailed clinical and EEG data, and indicates that CDKL5 gene mutations may represent a cause of severe or profound mental retardation and early-onset intractable seizures, also in boys. Screening for CDKL5 mutations is strongly recommended in individuals with these clinical features.

  1. CDKL5 Mutations in Boys With Encephalopathy and Early-Onset Intractable Epilepsy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2008-10-01

    Full Text Available Clinical and EEG data of 3 Italian boys (ages 3, 9, and 13 years with severe early-onset encephalopathy, mental retardation, facial dysmorphisms, and intractable epilepsy were found to carry missense mutations in the CDKL5 gene, in a report from Troina, Italy.

  2. CDKL5 and ARX mutations in males with early-onset epilepsy.

    Science.gov (United States)

    Mirzaa, Ghayda M; Paciorkowski, Alex R; Marsh, Eric D; Berry-Kravis, Elizabeth M; Medne, Livija; Alkhateeb, Asem; Grix, Art; Wirrell, Elaine C; Powell, Berkley R; Nickels, Katherine C; Burton, Barbara; Paras, Andrea; Kim, Katherine; Chung, Wendy; Dobyns, William B; Das, Soma

    2013-05-01

    Mutations in CDKL5 and ARX are known causes of early-onset epilepsy and severe developmental delay in males and females. Although numerous males with ARX mutations associated with various phenotypes have been reported in the literature, the majority of CDKL5 mutations have been identified in females with a phenotype characterized by early-onset epilepsy, severe global developmental delay, absent speech, and stereotypic hand movements. To date, only 10 males with CDKL5 mutations have been reported. Our retrospective study reports on the clinical, neuroimaging, and molecular findings of 18 males with early-onset epilepsy caused by either CDKL5 or ARX mutations. These 18 patients include eight new males with CDKL5 mutations and 10 with ARX mutations identified through sequence analysis of 266 and 346 males, respectively, at our molecular diagnostic laboratory. Our large dataset therefore expands on the number of reported males with CDKL5 mutations and highlights that aberrations of CDKL5 and ARX combined are an important consideration in the genetic forms of early-onset epilepsy in boys. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Early-onset parkinsonism associated with PINK1 mutations: frequency, genotypes, and phenotypes.

    NARCIS (Netherlands)

    Bonifati, V.; Rohe, C.F.; Breedveld, G.J.; Fabrizio, E.; Mari, M. De; Tassorelli, C.; Tavella, A.; Marconi, R.; Nicholl, D.; Chien, H.F.; Fincati, E.; Abbruzzese, G.; Marini, P.; Gaetano, A. De; Horstink, M.W.I.M.; Maat-Kievit, J.A.; Sampaio, C.; Antonini, A.; Stocchi, F.; Montagna, P.; Toni, V.; Guidi, M.; Dalla Libera, A.; Tinazzi, M.; Pandis, F. De; Goldwurm, S.; Klein, A. de; Barbosa, E.; Lopiano, L.; Martignoni, E.; Lamberti, P.; Vanacore, N.; Meco, G.; Oostra, B.A.

    2005-01-01

    OBJECTIVE: To assess the prevalence, nature, and associated phenotypes of PINK1 gene mutations in a large series of patients with early-onset (<50 years) parkinsonism. METHODS: The authors studied 134 patients (116 sporadic and 18 familial; 77% Italian) and 90 Italian controls. The whole PINK1

  4. Early onset of coronary artery disease after prenatal exposure to the Dutch famine

    NARCIS (Netherlands)

    Painter, Rebecca C.; de Rooij, Susanne R.; Bossuyt, Patrick M.; Simmers, Timothy A.; Osmond, Clive; Barker, David J.; Bleker, Otto P.; Roseboom, Tessa J.

    2006-01-01

    BACKGROUND: Limited evidence suggests that maternal undernutrition at the time of conception is associated with increased cardiovascular disease risk in adult offspring. OBJECTIVE: We investigated whether persons conceived during the Dutch famine of World War II had an early onset of coronary artery

  5. Memory in Early Onset Bipolar Disorder and Attention-Deficit/Hyperactivity Disorder: Similarities and Differences

    Science.gov (United States)

    Udal, Anne H.; Oygarden, Bjorg; Egeland, Jens; Malt, Ulrik F.; Groholt, Berit

    2012-01-01

    Differentiating between early-onset bipolar disorder (BD) and attention-deficit/hyperactivity disorder (ADHD) can be difficult. Memory problems are commonly reported in BD, and forgetfulness is among the diagnostic criteria for ADHD. We compared children and adolescents with BD (n = 23), ADHD combined type (ADHD-C; n = 26), BD + ADHD-C (n = 15),…

  6. Management of Very Early-onset Fetal Growth Restriction: Results from 92 Consecutive Cases.

    Science.gov (United States)

    Hoellen, Friederike; Beckmann, Annika; Banz-Jansen, Constanze; Weichert, Jan; Rody, Achim; Bohlmann, Michael K

    2016-01-01

    To evaluate management of early-onset intrauterine growth restriction (IUGR) and to define outcome according to obstetric setting. During an 11-year period (2000-2011), data of patients presenting with IUGR and preterm delivery of less than 30 weeks of gestation at a tertiary perinatal center were retrospectively reviewed. A total of 92 pregnancies were investigated. Delivery was indicated for fetal reasons in 38 out of 92 patients. Sixteen children of our cohort died within one year post partum, out of which eight had suffered from severe early-onset IUGR causing iatrogenic preterm delivery. Concerning the fetal outcome, gestational age at delivery and antenatal exposure to corticosteroids were found to be crucial. In some cases, respiratory distress syndrome prophylaxis and a "wait and see" approach to management in favor of a prolongation of the pregnancy might be favorable. Randomized prospective trials in early-onset IUGR with threatened preterm deliveries are needed in order to define guidelines for an individually tailored management of early-onset preterm infants. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  7. Early-onset periodontitis in Morocco is associated with the highly leukotoxic clone of Actinobacillus actinomycetemcomitans

    DEFF Research Database (Denmark)

    Haubek, Dorte; Ennibi, O.-K.; Poulsen, Knud

    2001-01-01

    A particular clone (JP2) of Actinobacillus actinomycetemcomitans with increased leukotoxin production has been isolated from individuals with early-onset periodontitis (EOP). The aim of this study was to determine the frequency of carriers of this clone and its association with EOP in Moroccan...

  8. Very early onset inflammatory bowel disease: Investigation of the IL-10 signaling pathway in Iranian children

    NARCIS (Netherlands)

    Nemati, Shahram; Teimourian, Shahram; Tabrizi, Mina; Najafi, Mehri; Dara, Naghi; Imanzadeh, Farid; Ahmadi, Mitra; Aghdam, Maryam Kazemi; Tavassoli, Mohmoud; Rohani, Pejman; Madani, Seyyed Ramin; de Boer, Martin; Kuijpers, T. W.; Roos, Dirk

    2017-01-01

    Background & aim: Comparing to adult inflammatory bowel disease (IBD), those with early onset manifestations have different features in terms of the underlying molecular pathology, the course of disease and the response to therapy. We investigated the IL-10 signaling pathway previously reported as

  9. Early-Onset Physical Frailty in Adults with Diabesity and Peripheral Neuropathy.

    Science.gov (United States)

    Tuttle, Lori J; Bittel, Daniel C; Bittel, Adam J; Sinacore, David R

    2017-12-07

    Diabesity (obesity and diabetes mellitus) has been identified as a potential contributor to early-onset frailty. Impairments contributing to early onset of physical frailty in this population are not well understood, and there is little evidence of the impact of peripheral neuropathy on frailty. The purpose of this study was to determine impairments that contribute to early-onset physical frailty in individuals with diabesity and peripheral neuropathy. We studied 105 participants, 82 with diabesity and peripheral neuropathy (57 years of age, body mass index [BMI] 31 kg/m 2 ); 13 with diabesity only (53 years of age, BMI 34 kg/m 2 ) and 10 obese controls (67 years of age, BMI 32 kg/m 2 ). Peripheral neuropathy was determined using Semmes Weinstein monofilaments; physical frailty was classified using the 9-item, modified Physical Performance Test; and knee extension and ankle plantarflexion peak torques were measured using isokinetic dynamometry. Participants with diabesity and peripheral neuropathy were 7.4 times more likely to be classified as physically frail. Impairments in lower-extremity function were associated with classification of frailty. Individuals with diabesity and peripheral neuropathy are particularly likely to be classified as frail. Earlier identification and interventions aimed at improving lower-extremity function may be important to mitigate the early-onset functional decline. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

  10. Early Onset Ageing and Service Preparation in People with Intellectual Disabilities: Institutional Managers' Perspective

    Science.gov (United States)

    Lin, Jin-Ding; Wu, Chia-Ling; Lin, Pei-Ying; Lin, Lan-Ping; Chu, Cordia M.

    2011-01-01

    Although longevity among older adults with intellectual disabilities is increasing, there is limited information on their premature aging related health characteristics and how it may change with increasing age. The present paper provides information of the institutional manager's perception on early onset aging and service preparation for this…

  11. Early-Onset Thrombocytopenia in Small-For-Gestational-Age Neonates: A Retrospective Cohort Study

    NARCIS (Netherlands)

    Fustolo-Gunnink, S. F.; Vlug, R. D.; Smits-Wintjens, V. E. H. J.; Heckman, E. J.; te Pas, A. B.; Fijnvandraat, K.; Lopriore, E.

    2016-01-01

    Thrombocytopenia is a common finding in small for gestational age (SGA) neonates and is thought to result from a unique pathophysiologic mechanism related to chronic intrauterine hypoxia. Our objective was to estimate the incidence and severity of early-onset thrombocytopenia in SGA neonates, and to

  12. Two-Year Diagnostic Stability in Early-Onset First-Episode Psychosis

    Science.gov (United States)

    Castro-Fornieles, Josefina; Baeza, Immaculada; de la Serna, Elena; Gonzalez-Pinto, Ana; Parellada, Mara; Graell, Montserrat; Moreno, Dolores; Otero, Soraya; Arango, Celso

    2011-01-01

    Background: Only one study has used a prospective method to analyze the diagnostic stability of first psychotic episodes in children and adolescents. The Child and Adolescent First-Episode Psychosis Study (CAFEPS) is a 2-year, prospective longitudinal study of early-onset first episodes of psychosis (EO-FEP). Aim: To describe diagnostic stability…

  13. Circulating asymmetric dimethylarginine and the risk of preeclampsia: a meta-analysis based on 1338 participants.

    Science.gov (United States)

    Yuan, Jing; Wang, Xinguo; Xie, Yudou; Wang, Yuzhi; Dong, Lei; Li, Hong; Zhu, Tongyu

    2017-07-04

    Patients with preeclampsia have higher circulating asymmetric dimethylarginine (ADMA). However, whether circulating ADMA is elevated before the diagnosis of preeclampsia has not been determined. A meta-analysis of observational studies that reported circulating ADMA level before the onset of preeclampsia was performed. Pubmed and Embase were searched. Standardized mean differences (SMD) with 95% confidence intervals (CI) were used to estimate the differences in circulating ADMA. A random effect model or a fixed effect model was applied depending on the heterogeneity. The predictive efficacy of circulating ADMA for the incidence of preeclampsia was also explored. Eleven comparisons with 1338 pregnant women were included. The pooled results showed that the circulating ADMA was significantly higher in women who subsequently developed preeclampsia as compared with those did not (SMD: 0.71, p preeclampsia, and retrieved moderate predictive efficacy. Circulating ADMA is elevated before the development of preeclampsia. Studies are needed to evaluate the predictive efficacy of ADMA for the incidence of preeclampsia.

  14. Parental and Child Characteristics Related to Early-Onset Disordered Eating: A Systematic Review.

    Science.gov (United States)

    Larsen, Pernille Stemann; Strandberg-Larsen, Katrine; Micali, Nadia; Andersen, Anne-Marie Nybo

    2015-01-01

    After participating in this activity, learners should be better able to: Evaluate the evidence regarding parental and child characteristics related to early-onset disordered eating. Eating disorders are rare in children, but disordered eating is common. Understanding the phenomenology of disordered eating in childhood can aid prevention of full-blown eating disorders. The purpose of this review is to systematically extract and synthesize the evidence on parental and child characteristics related to early-onset disordered eating. Systematic searches were conducted in PubMED/MEDLINE, EMBASE, and PsycInfo using the following search terms: eating disorder, disordered eating, problem eating, anorexia nervosa, bulimia nervosa, binge eating, child, preadolescent, and early onset. Studies published from 1990 to 2013 addressing parental and child characteristics of disordered eating in children aged 6 to 12 years were eligible for inclusion. The search was restricted to studies with cross-sectional, case-control, or longitudinal designs, studies in English, and with abstracts available. Forty-four studies fit these criteria. Most studies were based on community samples with a cross-sectional design. The included studies varied considerably in size, instruments used to assess early-onset disordered eating, and parental and child characteristics investigated. Important determinants included the following: higher body weight, previously reported disordered eating, body dissatisfaction, depression, parental disordered eating, and parental comments/concerns about child's weight and eating. The findings were inconsistent for sex, age, socioeconomic status, ethnicity, self-esteem/worth, and parental body weight. In conclusion, characteristics related to early-onset disordered eating have mainly been explored with a cross-sectional design. Full understanding of causal pathways will require good-quality longitudinal studies designed to address the influence of parental eating

  15. Determination of coagulopathy complicating severe preeclampsia ...

    African Journals Online (AJOL)

    Preeclampsia is defined as gestational hypertension plus proteinuria of 300 mg or more in 24 hour urine sample collection or persistent proteinuria of at least 30 mg/dl (at least 1+ on dipstick) in random urine samples.[5] Eclampsia is defined as the onset of seizures and/or unexplained coma during pregnancy, intrapartum.

  16. Early vs late age at onset frontotemporal dementia and frontotemporal lobar degeneration.

    Science.gov (United States)

    Seo, Sang Won; Thibodeau, Marie-Pierre; Perry, David C; Hua, Alice; Sidhu, Manu; Sible, Isabel; Vargas, Jose Norberto S; Gaus, Stephanie E; Rabinovici, Gil D; Rankin, Katherine D; Boxer, Adam L; Kramer, Joel H; Rosen, Howard J; Gorno-Tempini, Maria Luisa; Grinberg, Lea T; Huang, Eric J; DeArmond, Stephen J; Trojanowski, John Q; Miller, Bruce L; Seeley, William W

    2018-03-20

    To examine clinicopathologic correlations in early vs late age at onset frontotemporal dementia (FTD) and frontotemporal lobar degeneration (FTLD). All patients were clinically evaluated and prospectively diagnosed at the UCSF Memory and Aging Center. Two consecutive series were included: (1) patients with a clinically diagnosed FTD syndrome who underwent autopsy (cohort 1) and (2) patients with a primary pathologic diagnosis of FTLD, regardless of the clinical syndrome (cohort 2). These series were divided by age at symptom onset (cutoff 65 years). In cohort 1, 48 (25.3%) were 65 years or older at symptom onset. Pathologic causes of behavioral variant FTD (bvFTD) were similar in the early age at onset (EO) and late age at onset (LO) bvFTD groups. In corticobasal syndrome (CBS), however, the most common pathologic substrate differed according to age at onset: progressive supranuclear palsy (42.9%) in LO-CBS and Alzheimer disease (AD; 40.7%) in EO-CBS. In cohort 2, 57 (28.4%) were classified as LO-FTLD. Regarding FTLD major molecular classes, FTLD with transactive response DNA-binding protein of 43 kDa was most common in EO-FTLD (44.4%), whereas FTLD-tau (58.3%) was most common in LO-FTLD. Antemortem diagnosis of a non-FTD syndrome, usually AD-type dementia, was more frequent in LO-FTLD than EO-FTLD (19.3% vs 7.7%, p = 0.017). LO-FTLD was also associated with more prevalent comorbid pathologic changes. Of these, moderate to severe AD neuropathologic change and argyrophilic grain disease were overrepresented among patients who received an antemortem diagnosis of AD-type dementia. Patients with FTD and FTLD often develop symptoms after age 65, and age at onset represents an important consideration when making antemortem neuropathologic predictions. © 2018 American Academy of Neurology.

  17. Early-onset acute kidney injury is a poor prognostic sign for allogeneic SCT recipients.

    Science.gov (United States)

    Shingai, N; Morito, T; Najima, Y; Kobayashi, T; Doki, N; Kakihana, K; Ohashi, K; Ando, M

    2015-12-01

    Acute kidney injury (AKI) following stem-cell transplantation (SCT) contributes to a poor prognosis, yet its impact may vary depending on the timing of AKI onset. A prospective cohort study was performed to understand the significance of the onset timing in 103 allogeneic SCT (allo-SCT) recipients. AKI prior to stem-cell engraftment was defined as early AKI and subsequently occurring AKI as late AKI. Propensity score (PS) for early AKI was calculated using a logistic regression model to reduce confounding effects related to differences in clinical background between the early and late AKI groups. The cumulative incidences of early and late AKI were 22.3% and 54.9%, respectively. Non-relapse mortality (NRM) was 39.1% and 7.0%, and overall survival (OS) was 56.5% and 90.9% in early and late AKI at 100 days after AKI, respectively (PSCT was 41.5% and 19.1% in early and late AKI, respectively (P=0.048). Logistic regression analysis adjusted for the PS showed that early AKI was significantly associated with OS (odds ratio (95% confidence interval); 4.63 (1.15-21.4), P=0.031) but with neither NRM (1.25 (0.28-5.33), P=0.766) nor CKD (1.85 (0.41-8.60), P=0.422). In conclusion, early AKI may portend a poor survival for allo-SCT recipients.

  18. EARLY ONSET OF DELINQUENCY AND THE TRAJECTORY OF ALCOHOL-IMPAIRED DRIVING AMONG YOUNG MALES*

    Science.gov (United States)

    Zhang, Lening; Wieczorek, William F.; Welte, John W.

    2011-01-01

    Building upon the literature in developmental and life-course criminology, the present study assesses the possible association of age onset of delinquency with the trajectory of alcohol-impaired driving using data collected from the three waves of the Buffalo Longitudinal Survey of Young Men (BLSYM). It is argued that as a unique form of delinquency, alcohol-impaired driving among adolescents may be better understood in a broad context of adolescent delinquency involvement. The study adopts the general approach for the analysis of early onset of delinquency and criminal careers in developmental and life-course criminology and hypothesizes that early onset of delinquency is associated with a higher growth of alcohol-impaired driving over time among adolescents when age onsets of alcohol-impaired driving, drinking, and drug use are controlled. Our analysis with the HLM growth modeling method provides support for the hypothesis. Respondents who had an early start in delinquency were likely to have a faster growth of alcohol-impaired driving over the three waves of BLSYM, which implies that these respondents were likely to have a longer path of alcohol-impaired driving in their transition to adulthood. The implication of this finding is discussed. PMID:21831528

  19. Extent of Spine Deformity Predicts Lung Growth and Function in Rabbit Model of Early Onset Scoliosis.

    Directory of Open Access Journals (Sweden)

    J Casey Olson

    Full Text Available Early onset deformity of the spine and chest wall (initiated <8 years of age is associated with increased morbidity at adulthood relative to adolescent onset deformity of comparable severity. Presumably, inhibition of thoracic growth during late stage alveolarization leads to an irreversible loss of pulmonary growth and thoracic function; however the natural history of this disease from onset to adulthood has not been well characterized. In this study we establish a rabbit model of early onset scoliosis to establish the extent that thoracic deformity affects structural and functional respiratory development. Using a surgical right unilateral rib-tethering procedure, rib fusion with early onset scoliosis was induced in 10 young New Zealand white rabbits (3 weeks old. Progression of spine deformity, functional residual capacity, total lung capacity, and lung mass was tracked through longitudinal breath-hold computed tomography imaging up to skeletal maturity (28 weeks old. Additionally at maturity forced vital capacity and regional specific volume were calculated as functional measurements and histo-morphometry performed with the radial alveolar count as a measure of acinar complexity. Data from tethered rib rabbits were compared to age matched healthy control rabbits (N = 8. Results show unilateral rib-tethering created a progressive spinal deformity ranging from 30° to 120° curvature, the severity of which was strongly associated with pulmonary growth and functional outcomes. At maturity rabbits with deformity greater than the median (55° had decreased body weight (89%, right (59% and left (86% lung mass, right (74% and left (69% radial alveolar count, right lung volume at total lung capacity (60%, and forced vital capacity (75%. Early treatment of spinal deformity in children may prevent pulmonary complications in adulthood and these results provide a basis for the prediction of pulmonary development from thoracic structure. This model may

  20. Microvascular remodelling in preeclampsia: quantifying capillary rarefaction accurately and independently predicts preeclampsia.

    Science.gov (United States)

    Antonios, Tarek F T; Nama, Vivek; Wang, Duolao; Manyonda, Isaac T

    2013-09-01

    Preeclampsia is a major cause of maternal and neonatal mortality and morbidity. The incidence of preeclampsia seems to be rising because of increased prevalence of predisposing disorders, such as essential hypertension, diabetes, and obesity, and there is increasing evidence to suggest widespread microcirculatory abnormalities before the onset of preeclampsia. We hypothesized that quantifying capillary rarefaction could be helpful in the clinical prediction of preeclampsia. We measured skin capillary density according to a well-validated protocol at 5 consecutive predetermined visits in 322 consecutive white women, of whom 16 subjects developed preeclampsia. We found that structural capillary rarefaction at 20-24 weeks of gestation yielded a sensitivity of 0.87 with a specificity of 0.50 at the cutoff of 2 capillaries/field with the area under the curve of the receiver operating characteristic value of 0.70, whereas capillary rarefaction at 27-32 weeks of gestation yielded a sensitivity of 0.75 and a higher specificity of 0.77 at the cutoff of 8 capillaries/field with area under the curve of the receiver operating characteristic value of 0.82. Combining capillary rarefaction with uterine artery Doppler pulsatility index increased the sensitivity and specificity of the prediction. Multivariable analysis shows that the odds of preeclampsia are increased in women with previous history of preeclampsia or chronic hypertension and in those with increased uterine artery Doppler pulsatility index, but the most powerful and independent predictor of preeclampsia was capillary rarefaction at 27-32 weeks. Quantifying structural rarefaction of skin capillaries in pregnancy is a potentially useful clinical marker for the prediction of preeclampsia.

  1. Neuropsychological dysfunction in adults with early-onset obsessive-compulsive disorder: the search for a cognitive endophenotype

    Directory of Open Access Journals (Sweden)

    Jie Zhang

    2015-06-01

    Full Text Available Objective:Evidence suggests that early-onset obsessive-compulsive disorder (OCD is an etiologically distinct subtype of OCD. The objective of the present work was to search for neurocognitive endophenotypes of early-onset OCD based on assessments of attention, memory, and executive function in patients with the disorder and their unaffected siblings.Methods:We compared the performance of 40 adult patients with early-onset OCD, 40 of their unaffected siblings, and 40 unrelated healthy controls on a neuropsychological battery designed for this study. We searched for associations among test performance, demographic variables (age, sex and years of education and clinical symptoms of early-onset OCD.Results:Patients performed significantly worse than healthy controls on the Tower of Hanoi, and the Stroop and Wisconsin tests, indicating impairments in planning, mental flexibility and inhibitory control. The performance of the unaffected first-degree siblings of patients with early-onset OCD on the Stroop and Wisconsin tests also differed from that of healthy controls. Symptom severity in early-onset OCD was strongly correlated with performance on the Tower of Hanoi.Conclusions:Our findings support the existence of specific executive function deficits in patients with early-onset OCD. Relatives presented an intermediate phenotype between patients and controls, suggesting that executive functions such as mental flexibility and response inhibition may be considered candidate endophenotypes of early-onset OCD.

  2. High Prevalence of Long QT Syndrome Associated SCN5A Variants in Patients with Early-Onset Lone Atrial Fibrillation

    DEFF Research Database (Denmark)

    Olesen, Morten S; Yuan, Lei; Liang, Bo

    2012-01-01

    a mechanistic overlap between LQTS3 and early-onset lone AF. In 9 of 10 identified mutations and rare variants, we observed compromised biophysical properties affecting the transient peak current. CONCLUSIONS: In a cohort of patients with early-onset lone AF, we identified a high prevalence of SCN5A mutations...

  3. [The relationship between accommodative accuracy at different near-work distances and early-onset myopia].

    Science.gov (United States)

    Yu, Q W; Zhang, P; Zhou, S B; Hu, Y; Ji, M X; Luo, Y C; You, H L; Yao, Z X

    2016-07-01

    To observe the accommodative accuracy of children with early-onset myopia at different near-work distances, and discuss the relationship between accommodative accuracy and early-onset myopia. This was a case-control study. Thirty-seven emmetropic children, 41 early-onset myopic children without correction, and 39 early-onset myopic children with spectacles, aged 7 to 13 years, were included. Measures of refractive errors and accommodative accuracy at four near-work distances, including 50 cm, 40 cm, 30 cm, and 20 cm, were made using the binocular fusion cross cylinder (FCC) of an automatic phoropter. Most candidates showed accommodative lags, including the children with emmetropia. The ratio of lags in all candidates at different near-work distances was 75.21% (50 cm), 87.18% (40 cm), 92.31% (30 cm), and 98.29% (20 cm), respectively. All accommodative accuracies became worse, and the accommodative lag ratio and values of FCC increased, along with the shortening of the distance. The difference in accommodative accuracy among groups was statistically significant at 30 cm (χ(2)=7.852, P= 0.020) and 20 cm (χ(2)=6.480, P=0.039). The values of FCC among groups were significantly different at 30 cm (F=3.626, P=0.030) and 20 cm (F=3.703, P=0.028), but not at 50 cm and 40 cm (P>0.05). In addition, the FCC values of 30 cm and 20 cm had a statistically significant difference between myopic children without correction [(1.25±0.44) D and (1.76±0.43) D] and emmetropic children [(0.95±0.52) D and (1.41±0.58) D] (P=0.012, 0.008). The correlation between diopters of myopia and accommodative accuracy at different nearwork distances was not statistically significant (P>0.05). However, the correlation between diopters of myopia and the accommodative lag value (FCC) at 20 cm was statistically significant (r=0.246, P=0.028). The closer the near-work distance is, the worse the accommodative accuracy is. This is more significant in early-onset myopia, especially myopia without

  4. Precuneus atrophy in early-onset Alzheimer's disease: a morphometric structural MRI study

    International Nuclear Information System (INIS)

    Karas, Giorgos; Scheltens, Philip; Jones, Bethany; Rombouts, Serge; Schijndel, Ronald van; Klein, Martin; Flier, Wiesje van der; Vrenken, Hugo; Barkhof, Frederik

    2007-01-01

    Alzheimer's disease (AD) usually first presents in elderly patients, but may also develop at an earlier age. Patients with an early age at onset tend to present with complaints other than memory impairment, such as visuospatial problems or apraxia, which may reflect a different distribution of cortical involvement. In this study we set out to investigate whether age at onset in patients with AD determines the pattern of atrophy on cerebral MRI scans. We examined 55 patients with AD over a wide age range and analyzed their 3-D T1-weighted structural MRI scans in standard space using voxel-based morphometry (VBM). Regression analysis was performed to estimate loss of grey matter as a function of age, corrected for mini-mental state examination (MMSE) scores and sex. The VBM analyses identified multiple areas (including the temporal and parietal lobes), showing more atrophy with advancing age. By contrast, a younger age at onset was found to be associated with lower grey matter density in the precuneus. Regionalized volumetric analysis of this region confirmed the existence of disproportionate atrophy in the precuneus in patients with early-onset AD. Application of a multivariate model with precuneus grey matter density as input, showed that precuneal and hippocampal atrophy are independent from each other. Additionally, we found that a smaller precuneus is associated with impaired visuospatial functioning. Our findings support the notion that age at onset modulates the distribution of cortical involvement, and that disproportionate precuneus atrophy is more prominent in patients with a younger age of onset. (orig.)

  5. The Etiology and Clinical Course of Chronic Pancreatitis in Children With Early Onset of the Disease.

    Science.gov (United States)

    Wejnarska, Karolina; Kolodziejczyk, Elwira; Wertheim-Tysarowska, Katarzyna; Dadalski, Maciej; Sobczynska-Tomaszewska, Agnieszka; Kierkus, Jarosław; Bal, Jerzy; Rygiel, Agnieszka Magdalena; Oracz, Grzegorz

    2016-12-01

    The etiological factors of chronic pancreatitis (CP) in children differ from those in adults. To date, no study has assessed the clinical course of CP in young children. The aim of our study was to evaluate the etiology and the clinical presentation of the disease in children with disease onset before 5 years of age in comparison to later-onset of CP. A total of 276 children with CP, hospitalized from 1988 to 2015, were enrolled in the study. Data on presentation, diagnostic findings, and treatment were reviewed. Two hundred sixty patients were screened for the most frequent mutations in major pancreatitis-associated genes, such as cationic trypsinogen/serine protease gene (PRSS1), serine protease inhibitor, Kazal type 1 gene (SPINK1), and cystic fibrosis transmembrane conductance regulator gene (CFTR). The disease onset before the age of 5 years occurred in 51 patients (group 1), the later onset in 225 patients (group 2). We found no significant discrepancies in distribution of the etiological factors between groups. The youngest patients (group 1) had more pancreatitis episodes (median 5.0 vs 3.00; P pancreatic function. Early- and later-onset pancreatitis have similar etiological factors with predominance of gene mutations. The most frequent mutation found was p.Asn34Ser (N34S) in SPINK1 gene. The clinical presentation differed in number of pancreatitis episodes and frequency of surgeries.

  6. [Analysis of gene mutation of early onset epileptic spasm with unknown reason].

    Science.gov (United States)

    Yang, X; Pan, G; Li, W H; Zhang, L M; Wu, B B; Wang, H J; Zhang, P; Zhou, S Z

    2017-11-02

    Objective: To summarize the gene mutation of early onset epileptic spasm with unknown reason. Method: In this prospective study, data of patients with early onset epileptic spasm with unknown reason were collected from neurological department of Children's Hospital of Fudan University between March 2016 and December 2016. Patients with known disorders such as infection, metabolic, structural, immunological problems and known genetic mutations were excluded. Patients with genetic disease that can be diagnosed by clinical manifestations and phenotypic characteristics were also excluded. Genetic research methods included nervous system panel containing 1 427 epilepsy genes, whole exome sequencing (WES), analysis of copy number variation (CNV) and karyotype analysis of chromosome. The basic information, phenotypes, genetic results and the antiepileptic treatment of patients were analyzed. Result: Nine of the 17 cases with early onset epileptic spasm were boys and eight were girls. Patients' age at first seizure onset ranged from 1 day after birth to 8 months (median age of 3 months). The first hospital visit age ranged from 1 month to 2 years (median age of 4.5 months). The time of following-up ranged from 8 months to 3 years and 10 months. All the 17 patients had early onset epileptic spasm. Video electroencephalogram was used to monitor the spasm seizure. Five patients had Ohtahara syndrome, 10 had West syndrome, two had unclear classification. In 17 cases, 10 of them had detected pathogenic genes. Nine cases had point mutations, involving SCN2A, ARX, UNC80, KCNQ2, and GABRB3. Except one case of mutations in GABRB3 gene have been reported, all the other cases had new mutations. One patient had deletion mutation in CDKL5 gene. One CNV case had 6q 22.31 5.5MB repeats. Ten cases out of 17 were using 2-3 antiepileptic drugs (AEDs) and the drugs had no effect. Seven cases used adrenocorticotropic hormone (ACTH) and prednisone besides AEDs (a total course for 8 weeks

  7. Decision making and executive function in male adolescents with early-onset or adolescence-onset conduct disorder and control subjects.

    Science.gov (United States)

    Fairchild, Graeme; van Goozen, Stephanie H M; Stollery, Sarah J; Aitken, Michael R F; Savage, Justin; Moore, Simon C; Goodyer, Ian M

    2009-07-15

    Although conduct disorder (CD) is associated with an increased susceptibility to substance use disorders, little is known about decision-making processes or reward mechanisms in CD. This study investigated decision making under varying motivational conditions in CD. Performances on the Risky Choice Task (RCT) and the Wisconsin Card Sorting Test (WCST) were assessed in 156 adolescents (84 control subjects, 34 with adolescence-onset CD, and 38 with early-onset CD). The RCT was performed twice, once under normal motivational conditions and once under conditions of increased motivation and psychosocial stress. Increased motivation and stress led to more cautious decision making and changes in framing effects on the RCT in all groups, although such effects were least pronounced in the early-onset CD group. Participants from both CD subgroups selected the risky choice more frequently than control subjects. Under normal motivational conditions, early-onset CD participants chose the risky choice more frequently in trials occurring after small gains, relative to control subjects and adolescence-onset CD participants. Following adjustment for IQ differences, the groups did not differ significantly in terms of WCST performance. Differences in decision making between control subjects and individuals with CD suggest that the balance between sensitivity to reward and punishment is shifted in this disorder, particularly the early-onset form. Our data on modulation of decision making according to previous outcomes suggest altered reward mechanisms in early-onset CD. The WCST data suggest that impairments in global executive function do not underlie altered decision making in CD.

  8. Early-Onset Creutzfeldt-Jakob Disease Mimicking Immune-Mediated Encephalitis

    Directory of Open Access Journals (Sweden)

    Wietse A. Wiels

    2018-04-01

    Full Text Available ObjectivesThe objective of this study is to explore the clinical, radiological, and pathological manifestations of a rare subtype of prion disease and their implication for differential diagnosis in case of an early onset neuropsychiatric deterioration.MethodsWe discuss a patients’ clinical history, as well as the string of investigations and symptomatological evolution that finally led to a pathological diagnosis.ResultsOur patient had the extremely rare VV1 type sporadic Creutzfeldt-Jakob disease (sCJD. We explain the differential diagnosis of progressive encephalomyelitis with rigidity and myoclonus and its implications for treatment.ConclusionsCJD, especially the VV1 subtype, can present at an early age with an insidious psychiatric onset. Classical findings of prion disease—14-3-3 protein, PSWC on electroencephalography, and magnetic resonance imaging patterns—are not always present. The presence of neural autoantibodies does not always implicate pathogenicity in the presence of other neurological/neurodegenerative conditions.

  9. The reduction in circulating levels of melatonin may be associated with the development of preeclampsia.

    Science.gov (United States)

    Zeng, K; Gao, Y; Wan, J; Tong, M; Lee, A C; Zhao, M; Chen, Q

    2016-11-01

    Placental dysfunction and oxidative stress contribute to the pathogenesis of preeclampsia, which is a pregnancy-specific disorder. It has been suggested that the incidence of preeclampsia has a seasonal variation. Melatonin, as a seasonal factor, has been suggested to be involved in a successful pregnancy. In this study, we investigated the association of circulating levels of melatonin with preeclampsia. Serum was collected from women with preeclampsia (n=113) and gestation-matched healthy pregnant women, and the levels of melatonin were measured. In addition, the expression of melatonin receptors was examined in preeclamptic placentae (n=27). The association of the incidence of preeclampsia and seasonal variation was also analysed from 1491 women with preeclampsia within 77 745 healthy pregnancies. The serum levels of melatonin were significantly reduced in women with preeclampsia at presentation and these reduced serum levels of melatonin were not associated with the severity or time onset of preeclampsia nor with seasonal variation. The expression of melatonin receptor, MT1 was reduced in preeclamptic placentae. The incidence of preeclampsia was did exhibit seasonal variation, but this was largely due to the increase in the incidence of mild or late-onset preeclampsia. Our results demonstrate that reduced melatonin levels are associated with the development of preeclampsia but that the circulating levels of melatonin do not appear to be subject to seasonal variation during pregnancy.

  10. Adenosine and preeclampsia.

    Science.gov (United States)

    Salsoso, Rocío; Farías, Marcelo; Gutiérrez, Jaime; Pardo, Fabián; Chiarello, Delia I; Toledo, Fernando; Leiva, Andrea; Mate, Alfonso; Vázquez, Carmen M; Sobrevia, Luis

    2017-06-01

    Adenosine is an endogenous nucleoside with pleiotropic effects in different physiological processes including circulation, renal blood flow, immune function, or glucose homeostasis. Changes in adenosine membrane transporters, adenosine receptors, and corresponding intracellular signalling network associate with development of pathologies of pregnancy, including preeclampsia. Preeclampsia is a cause of maternal and perinatal morbidity and mortality affecting 3-5% of pregnancies. Since the proposed mechanisms of preeclampsia development include adenosine-dependent biological effects, adenosine membrane transporters and receptors, and the associated signalling mechanisms might play a role in the pathophysiology of preeclampsia. Preeclampsia associates with increased adenosine concentration in the maternal blood and placental tissue, likely due to local hypoxia and ischemia (although not directly demonstrated), microthrombosis, increased catecholamine release, and platelet activation. In addition, abnormal expression and function of equilibrative nucleoside transporters is described in foetoplacental tissues from preeclampsia; however, the role of adenosine receptors in the aetiology of this disease is not well understood. Adenosine receptors activation may be related to abnormal trophoblast invasion, angiogenesis, and ischemia/reperfusion mechanisms in the placenta from preeclampsia. These mechanisms may explain only a low fraction of the associated abnormal transformation of spiral arteries in preeclampsia, triggering cellular stress and inflammatory mediators release from the placenta to the maternal circulation. Although increased adenosine concentration in preeclampsia may be a compensatory or adaptive mechanism favouring placental angiogenesis, a poor angiogenic state is found in preeclampsia. Thus, preeclampsia-associated complications might affect the cell response to adenosine due to altered expression and activity of adenosine receptors, membrane transporters

  11. Early onset diabetes-genetic and hormonal analysis in pakistan population

    International Nuclear Information System (INIS)

    Wahid, M.; Kamran, M.

    2016-01-01

    Background: Mitochondrial DNA mutation and hormonal imbalance is involved in the pathogenesis of early onset diabetes but data is lacking in Pakistani population. The study was planned to delineate the clinical presentation of early onset diabetes with possible hormonal and genetic etiological factors and aascertain the possible etiological role of insulin and glucagon in these patients either on oral hypoglycaemic or subcutaneous insulin therapy. Methods: Retrospective, analytical case control study with conventional sampling technique carried at Centre for Research in Experimental and Applied Medicine (CREAM) affiliated with the department of Biochemistry and Molecular Biology, Army Medical College Rawalpindi from Dec 2006 to July 2011. Study included the patients (20-35 years of age) with early onset diabetes on oral hypoglycemic (n=240), insulin therapy (n=280), and compared with non-diabetic healthy controls (n=150). A fragment surrounding tRNALeu (UUR) gene was amplified by AmpliTaq from mtDNA which was extracted from peripheral blood leucocytes. Then it was subjected to restriction endonucleases, ApaI for A3242G mutation and HaeIII for G3316A mutation detection. Plasma glucose, glycosylated Hb, osmolality, insulin and glucagon levels along with ABGs analysis was also done. Results: Non diabetic controls comprised of 51% males and 49% females, diabetics on oral hypoglycemic 60% males and 40 % females and on insulin therapy 54% males and 46% females. Insulin dependent diabetics had statistically significant hyperglucagonemia, acidemia and bicarbonate deficit. MtDNA A3242G and G3316A mutations were not detected. Conclusion: relative hyperglucagonemia and acidemia in Insulin dependent diabetics was a potent threat leading to DKA. The absence of two mtDNA mutations in ND1 gene rules out the possibility of involvement of these mutations in early onset diabetes in Pakistani population. (author)

  12. Alcohol intake and early-onset basal cell carcinoma in a case-control study.

    Science.gov (United States)

    Zhang, Y; Ferrucci, L M; Cartmel, B; Molinaro, A M; Leffell, D J; Bale, A E; Mayne, S T

    2014-12-01

    Previous epidemiological studies of overall alcohol intake and basal cell carcinoma (BCC) are inconsistent, with some evidence for differences by type of alcoholic beverage. While alcohol may enhance the carcinogenicity of ultraviolet (UV) radiation, this has not been evaluated in existing epidemiological studies. To evaluate alcohol intake in relation to early-onset BCC, and explore potential interactions with UV exposure. Basal cell carcinoma cases (n = 380) and controls with benign skin conditions (n = 390) under 40 years of age were identified through Yale Dermatopathology. Participants provided information on lifetime alcohol intake, including type of beverage, during an in-person interview. Self-reported data on indoor tanning and outdoor sunbathing were used to categorize UV exposure. We calculated odds ratios (OR) and 95% confidence intervals (CIs) using unconditional multivariate logistic regression in the full sample and in women only. There was no statistically significant association between lifetime alcohol intake and early-onset BCC overall [above median intake vs. no regular alcohol intake (OR 1·10, 95% CI 0·69-1·73)] or in women only (OR 1·21, 95% CI 0·73-2·01). Similarly, intake of red wine, white wine, beer or spirits and mixed drinks was not associated with early-onset BCC. In exploratory analyses, we saw limited evidence for an interaction (P(interaction) = 0·003), with highest risk for high alcohol and high UV exposures, especially in women, but subgroup risk estimates had wide and overlapping CIs. Overall, we did not observe any clear association between lifetime alcohol intake and early-onset BCC. © 2014 British Association of Dermatologists.

  13. Psychiatric Symptomatology in Early-Onset Binswanger’s Disease: Two Case Reports

    Directory of Open Access Journals (Sweden)

    R. M. Lawrence

    1995-01-01

    Full Text Available We describe two cases of Binswanger's disease of pre-senile onset which presented with affective and psychotic symptoms well before the appearance of cognitive deterioration and neurological signs, initially evading an accurate diagnosis. Psychiatrists should be aware of white matter disease and its role in the pathogenesis of psychiatric illness. Particular attention should be given to a history of hypertension as a risk factor in the early identification of these cases.

  14. Labour onset and early labour. An exploration of first-time mothers’ and midwives’ experiences

    OpenAIRE

    Eri, Tine Schauer

    2011-01-01

    This dissertation is about how women experience waiting for the onset of labour, and how first-time mothers and midwives communicate during the early phases of labour. Most women in Norway give birth in public hospitals, which is the context used for this study, with the experiences explored within a scientific tradition of lifeworld research. Seventeen women and 18 midwives participated in the study. The empirical material stems from diaries, observations of admissions and in-...

  15. Prediction and primary prevention of pre-eclampsia

    NARCIS (Netherlands)

    Thangaratinam, Shakila; Langenveld, Josie; Mol, Ben W.; Khan, Khalid S.

    2011-01-01

    Pre-eclampsia is associated with increased maternal and perinatal mortality and morbidity. Early recognition of women at risk of pre-eclampsia will enable the identification of high-risk women who may benefit from enhanced surveillance and prophylaxis. In this chapter, we summarise the accuracy of

  16. Variants of early-onset restrictive eating disturbances in middle childhood.

    Science.gov (United States)

    Kurz, Susanne; van Dyck, Zoé; Dremmel, Daniela; Munsch, Simone; Hilbert, Anja

    2016-01-01

    This study sought to determine the factor structure of the newly developed self-report screening questionnaire Eating Disturbances in Youth-Questionnaire (EDY-Q) as well as to report the distribution of variants of early-onset restrictive eating disturbances characteristic of avoidant/restrictive food intake disorder (ARFID) in a middle childhood population sample. Using the EDY-Q, a total of 1,444 children aged 8-13 years were screened in elementary schools in Switzerland via self-report. The factor analysis of the 12 items covering ARFID related symptoms was performed using a principal component analysis (PCA). The PCA showed a four factor solution, with clear allocation to the scales covering three variants of early-onset restrictive eating disturbances and weight problems. Inadequate overall food intake was reported by 19.3% of the children, a limited accepted amount of food by 26.1%, and food avoidance based on a specific underlying fear by 5.0%. The postulated factor structure of the EDY-Q was confirmed, further supporting the existence of distinct variants of early-onset restrictive eating disturbances. Avoidant/restrictive eating behavior seems to be a common experience in middle childhood, but results have to be confirmed using validated interviews. © 2015 Wiley Periodicals, Inc.

  17. A girl with early-onset epileptic encephalopathy associated with microdeletion involving CDKL5.

    Science.gov (United States)

    Saitsu, Hirotomo; Osaka, Hitoshi; Nishiyama, Kiyomi; Tsurusaki, Yoshinori; Doi, Hiroshi; Miyake, Noriko; Matsumoto, Naomichi

    2012-05-01

    Recent studies have shown that aberrations of CDKL5 in female patients cause early-onset intractable seizures, severe developmental delay or regression, and Rett syndrome-like features. We report on a Japanese girl with early-onset epileptic encephalopathy, hypotonia, developmental regression, and Rett syndrome-like features. The patient showed generalized tonic seizures, and later, massive myoclonus induced by phone and light stimuli. Brain magnetic resonance imaging showed no structural brain anomalies but cerebral atrophy. Electroencephalogram showed frontal dominant diffuse poly spikes and waves. Through copy number analysis by genomic microarray, we found a microdeletion at Xp22.13. A de novo 137-kb deletion, involving exons 5-21 of CDKL5, RS1, and part of PPEF1 gene, was confirmed by quantitative PCR and breakpoint specific PCR analyses. Our report suggests that the clinical features associated with CDKL5 deletions could be implicated in Japanese patients, and that genetic testing of CDKL5, including both sequencing and deletion analyses, should be considered in girls with early-onset epileptic encephalopathy and RTT-like features. Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  18. High-Definition transcranial direct current stimulation in early onset epileptic encephalopathy: a case study.

    Science.gov (United States)

    Meiron, Oded; Gale, Rena; Namestnic, Julia; Bennet-Back, Odeya; David, Jonathan; Gebodh, Nigel; Adair, Devin; Esmaeilpour, Zeinab; Bikson, Marom

    2018-01-01

    Early onset epileptic encephalopathy is characterized by high daily seizure-frequency, multifocal epileptic discharges, severe psychomotor retardation, and death at infancy. Currently, there are no effective treatments to alleviate seizure frequency and high-voltage epileptic discharges in these catastrophic epilepsy cases. The current study examined the safety and feasibility of High-Definition transcranial direct current stimulation (HD-tDCS) in reducing epileptiform activity in a 30-month-old child suffering from early onset epileptic encephalopathy. HD-tDCS was administered over 10 intervention days spanning two weeks including pre- and post-intervention video-EEG monitoring. There were no serious adverse events or side effects related to the HD-tDCS intervention. Frequency of clinical seizures was not significantly reduced. However, interictal sharp wave amplitudes were significantly lower during the post-intervention period versus baseline. Vital signs and blood biochemistry remained stable throughout the entire study. These exploratory findings support the safety and feasibility of 4 × 1 HD-tDCS in early onset epileptic encephalopathy and provide the first evidence of HD-tDCS effects on paroxysmal EEG features in electroclinical cases under the age of 36 months. Extending HD-tDCS treatment may enhance electrographic findings and clinical effects.

  19. The BRCA1 and BRCA2 Genes in Early-Onset Breast Cancer Patients.

    Science.gov (United States)

    Saleem, Mohamed; Ghazali, Mohd Bazli; Wahab, Md Azlan Mohamed Abdul; Yusoff, Narazah Mohd; Mahsin, Hakimah; Seng, Ch'ng Ewe; Khalid, Imran Abdul; Rahman, Mohd Nor Gohar; Yahaya, Badrul Hisham

    2018-04-24

    Approximately 5-10% of breast cancers are attributable to genetic susceptibility. Mutations in the BRCA1 and BRCA2 genes are the best known genetic factors to date. The goal of this study was to determine the structure and distribution of haplotypes of the BRCA1 and BRCA2 genes in early-onset breast cancer patients. We enrolled 70 patients diagnosed with early-onset breast cancer. A total of 21 SNPs (11 on BRCA1 and 10 on BRCA2) and 1 dinucleotide deletion on BRCA1 were genotyped using nested allele-specific PCR methods. Linkage disequilibrium (LD) analysis was conducted, and haplotypes were deduced from the genotype data. Two tightly linked LD blocks were observed on each of the BRCA1 and BRCA2 genes. Variant-free haplotypes (TAT-AG for BRCA1 and ATA-AAT for BRCA2) were observed at a frequency of more than 50% on each gene along with variable frequencies of derived haplotypes. The variant 3'-subhaplotype CGC displayed strong LD with 5'-subhaplotypes GA, AA, and GG on BRCA1 gene. Haplotypes ATA-AGT, ATC-AAT, and ATA-AAC were the variant haplotypes frequent on BRCA2 gene. Although the clinical significance of these derived haplotypes has not yet been established, it is expected that some of these haplotypes, especially the less frequent subhaplotypes, eventually will be shown to be indicative of a predisposition to early-onset breast cancer.

  20. Long term functioning in early onset psychosis: Two years prospective follow-up study

    Directory of Open Access Journals (Sweden)

    Taha Ghada RA

    2011-07-01

    Full Text Available Abstract Background There were few studies on the outcome of schizophrenia in developing countries. Whether the outcome is similar to or different from developed world is still a point for research. The main aim of the current study was to know if patients with early onset non affective psychosis can behave and function properly after few years from start of the illness or not. Other aims included investigation of possible predictors and associated factors with remission and outcome. Method The study prospectively investigated a group of 56 patients with onset of psychosis during childhood or adolescence. Diagnosis made according to DSM-IV criteria and included; schizophrenia, psychotic disorder not otherwise specified and acute psychosis. Severity of psychosis was measured by PANSS. Measures of the outcome included; remission criteria of Andreasen et al 2005, the children's global assessment scale and educational level. Results Analysis of data was done for only 37 patients. Thirty patients diagnosed as schizophrenia and 7 with Psychotic disorder not otherwise specified. Mean duration of follow up was 38.4 +/- 16.9 months. At the end of the study, 6 patients (16.2% had one episode, 23(62.1% had multiple episodes and 8 (21.6% continuous course. Nineteen patients (51.4% achieved full remission, and only 11(29.7% achieved their average educational level for their age. Twenty seven percent of the sample had good outcome and 24.3% had poor outcome. Factors associated with non remission and poor outcome included gradual onset, low IQ, poor premorbid adjustment, negative symptoms at onset of the illness and poor adherence to drugs. Moreover, there was tendency of negative symptoms at illness start to predict poor outcome. Conclusion Some patients with early onset non affective psychosis can behave and function properly after few years from the start of the illness. Although remission is a difficult target in childhood psychosis, it is still achievable.

  1. Neuropeptide Y gene polymorphisms confer risk of early-onset atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Svati H Shah

    2009-01-01

    Full Text Available Neuropeptide Y (NPY is a strong candidate gene for coronary artery disease (CAD. We have previously identified genetic linkage to familial CAD in the genomic region of NPY. We performed follow-up genetic, biostatistical, and functional analysis of NPY in early-onset CAD. In familial CAD (GENECARD, N = 420 families, we found increased microsatellite linkage to chromosome 7p14 (OSA LOD = 4.2, p = 0.004 in 97 earliest age-of-onset families. Tagged NPY SNPs demonstrated linkage to CAD of a 6-SNP block (LOD = 1.58-2.72, family-based association of this block with CAD (p = 0.02, and stronger linkage to CAD in the earliest age-of-onset families. Association of this 6-SNP block with CAD was validated in: (a 556 non-familial early-onset CAD cases and 256 controls (OR 1.46-1.65, p = 0.01-0.05, showing stronger association in youngest cases (OR 1.84-2.20, p = 0.0004-0.09; and (b GENECARD probands versus non-familial controls (OR 1.79-2.06, p = 0.003-0.02. A promoter SNP (rs16147 within this 6-SNP block was associated with higher plasma NPY levels (p = 0.04. To assess a causal role of NPY in atherosclerosis, we applied the NPY1-receptor-antagonist BIBP-3226 adventitially to endothelium-denuded carotid arteries of apolipoprotein E-deficient mice; treatment reduced atherosclerotic neointimal area by 50% (p = 0.03. Thus, NPY variants associate with atherosclerosis in two independent datasets (with strong age-of-onset effects and show allele-specific expression with NPY levels, while NPY receptor antagonism reduces atherosclerosis in mice. We conclude that NPY contributes to atherosclerosis pathogenesis.

  2. The affective dimension of early-onset psychosis and its relationship with suicide.

    Science.gov (United States)

    Sanchez-Gistau, Vanessa; Baeza, Inmaculada; Arango, Celso; González-Pinto, Ana; de la Serna, Elena; Parellada, Mara; Graell, Montserrat; Paya, Beatriz; Llorente, Cloe; Castro-Fornieles, Josefina

    2015-07-01

    The affective dimension has scarcely been studied in early-onset psychosis. Our aims were to investigate the prevalence and type of affective symptoms in the prodromal and acute phases of early-onset psychosis and to examine their relationship with suicide. We also sought to establish whether the presence of premorbid antecedents or the presence of affective symptoms during the prodromal and acute phase might predict a later diagnosis of bipolar disorder (BP) or schizophrenia (SZ). Participants were 95 youths, aged 9-17 years, experiencing a first episode of a psychotic disorder (FEP) according to DSM-IV criteria. Prodromal affective symptoms in the year prior to the onset of full-blown psychosis were assessed by means of the K-SADS. Affective symptoms during the acute episode were evaluated using the Hamilton Depression Rating Scale and the Young Mania Rating Scale. Suicidality was assessed during the acute episode and at 6 and 12 months. Half of the patients experienced affective symptoms during the prodrome, with depressive symptoms being the most frequently reported. During the acute episode, 23.2% presented depressive, 41.4% mixed and 18.9% manic symptoms. After logistic regression analysis, only the presence of depressive symptoms was significantly associated with suicidality during the 12 months following the FEP. Neither early premorbid antecedents nor the prevalence or type of affective symptoms during the FEP predicted a diagnosis of BP or SZ at 12 months. However, both depressive and manic prodromal symptoms were associated with a later diagnosis of BP. The FEP of both SZ and BP is preceded by an identifiable prodromal phase. Early detection programs should target young people at clinical risk for the extended psychosis phenotype. The high prevalence of affective symptoms during the early phases of psychosis may encourage clinicians to identify and treat them in order to prevent suicide behaviour. © 2014 Association for Child and Adolescent Mental

  3. CORRELATION OF SPOT URINE ALBUMIN AND 12-HOUR URINE PROTEIN WITH 24-HOUR URINE PROTEIN IN PRE-ECLAMPSIA

    Directory of Open Access Journals (Sweden)

    S. Vinayachandran

    2017-11-01

    Full Text Available BACKGROUND Pre-eclampsia is defined as the development of new-onset hypertension in the second half of pregnancy often accompanied by new-onset proteinuria with other signs and symptoms. Proteinuria is defined by the excretion of 300 mg or more of protein in a 24-hour urine collection. To avoid time consumed in collection of 24-hour urine specimens, efforts have been made to develop faster methods to determine concentration of urine protein. Preliminary studies have suggested that 12-hour urine protein collection maybe adequate for evaluation of pre-eclampsia with advantage of early diagnosis and treatment of pre-eclampsia as well as potential for early hospital discharge and increased compliance with specimen collection. The aim of the study is to evaluate and correlate spot urine albumin and 12-hour urine protein with 24-hour urine protein in pre-eclampsia. MATERIALS AND METHODS A diagnostic evaluation study- a 24-hour urine protein, 12-hour urine protein and spot urine albumin results are analysed. Correlation of 12-hour urine protein and spot urine albumin with 24-hour urine protein is analysed using SPSS software. The strength of correlation was measured by Pearson’s correlation coefficient (r. Student’s t-test and Chi-square tests were used to compare patients with and without 24-hour urine protein ≥300 mg. Probability value of 165 mg with 24-hour urine protein ≥300 mg suggest that this test has role in the evaluation of women with suspected pre-eclampsia and could be substituted for 24-hour urine protein as a simple, faster and cheaper method.

  4. Mutations of maturity-onset diabetes of the young (MODY) genes in Thais with early-onset type 2 diabetes mellitus.

    Science.gov (United States)

    Plengvidhya, Nattachet; Boonyasrisawat, Watip; Chongjaroen, Nalinee; Jungtrakoon, Prapaporn; Sriussadaporn, Sutin; Vannaseang, Sathit; Banchuin, Napatawn; Yenchitsomanus, Pa-thai

    2009-06-01

    Six known genes responsible for maturity-onset diabetes of the young (MODY) were analysed to evaluate the prevalence of their mutations in Thai patients with MODY and early-onset type 2 diabetes. Fifty-one unrelated probands with early-onset type 2 diabetes, 21 of them fitted into classic MODY criteria, were analysed for nucleotide variations in promoters, exons, and exon-intron boundaries of six known MODY genes, including HNF-4alpha, GCK, HNF-1alpha, IPF-1, HNF-1beta, and NeuroD1/beta2, by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method followed by direct DNA sequencing. Missense mutations or mutations located in regulatory region, which were absent in 130 chromosomes of non-diabetic controls, were classified as potentially pathogenic mutations. We found that mutations of the six known MODY genes account for a small proportion of classic MODY (19%) and early-onset type 2 diabetes (10%) in Thais. Five of these mutations are novel including GCK R327H, HNF-1alpha P475L, HNF-1alphaG554fsX556, NeuroD1-1972 G > A and NeuroD1 A322N. Mutations of IPF-1 and HNF-1beta were not identified in the studied probands. Mutations of the six known MODY genes may not be a major cause of MODY and early-onset type 2 diabetes in Thais. Therefore, unidentified genes await discovery in a majority of Thai patients with MODY and early-onset type 2 diabetes.

  5. The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy.

    Science.gov (United States)

    Fehr, Stephanie; Wilson, Meredith; Downs, Jenny; Williams, Simon; Murgia, Alessandra; Sartori, Stefano; Vecchi, Marilena; Ho, Gladys; Polli, Roberta; Psoni, Stavroula; Bao, Xinhua; de Klerk, Nick; Leonard, Helen; Christodoulou, John

    2013-03-01

    The clinical understanding of the CDKL5 disorder remains limited, with most information being derived from small patient groups seen at individual centres. This study uses a large international data collection to describe the clinical profile of the CDKL5 disorder and compare with Rett syndrome (RTT). Information on individuals with cyclin-dependent kinase-like 5 (CDKL5) mutations (n=86) and females with MECP2 mutations (n=920) was sourced from the InterRett database. Available photographs of CDKL5 patients were examined for dysmorphic features. The proportion of CDKL5 patients meeting the recent Neul criteria for atypical RTT was determined. Logistic regression and time-to-event analyses were used to compare the occurrence of Rett-like features in those with MECP2 and CDKL5 mutations. Most individuals with CDKL5 mutations had severe developmental delay from birth, seizure onset before the age of 3 months and similar non-dysmorphic features. Less than one-quarter met the criteria for early-onset seizure variant RTT. Seizures and sleep disturbances were more common than in those with MECP2 mutations whereas features of regression and spinal curvature were less common. The CDKL5 disorder presents with a distinct clinical profile and a subtle facial, limb and hand phenotype that may assist in differentiation from other early-onset encephalopathies. Although mutations in the CDKL5 gene have been described in association with the early-onset variant of RTT, in our study the majority did not meet these criteria. Therefore, the CDKL5 disorder should be considered separate to RTT, rather than another variant.

  6. Problem drinking among Flemish students: beverage type, early drinking onset and negative personal & social consequences.

    Science.gov (United States)

    De Bruyn, Sara; Wouters, Edwin; Ponnet, Koen; Van Damme, Joris; Maes, Lea; Van Hal, Guido

    2018-02-12

    Although alcohol is socially accepted in most Western societies, studies are clear about its associated negative consequences, especially among university and college students. Studies on the relationship between alcohol-related consequences and both beverage type and drinking onset, however, are scarce, especially in a European context. The aim of this research was, therefore, twofold: (1) What is the relationship between beverage type and the negative consequences experienced by students? and (2) Are these consequences determined by early drinking onset? We will examine these questions within the context of a wide range of alcohol-related consequences. The analyses are based on data collected by the inter-university project 'Head in the clouds?', measuring alcohol use among students in Flanders (Belgium). In total, a large dataset consisting of information from 19,253 anonymously participating students was available. Negative consequences were measured using a shortened version of the Core Alcohol and Drug Survey (CADS_D). Data were analysed using negative binomial regression. Results vary depending on the type of alcohol-related consequences: Personal negative consequences occur frequently among daily beer drinkers. However, a high rate of social negative consequences was recorded for both daily beer drinkers and daily spirits drinkers. Finally, early drinking onset was significantly associated with both personal and social negative consequences, and this association was especially strong between beer and spirits drinking onset and social negative consequences. Numerous negative consequences, both personal and social, are related to frequent beer and spirits drinking. Our findings indicate a close association between drinking beer and personal negative consequences as well as between drinking beer and/or spirits and social negative consequences. Similarly, early drinking onset has a major influence on the rates of both personal and social negative consequences

  7. Characteristics of the spouse caregiving experience: Comparison between early- and late-onset dementia.

    Science.gov (United States)

    Wawrziczny, Emilie; Berna, Guillaume; Ducharme, Francine; Kergoat, Marie-Jeanne; Pasquier, Florence; Antoine, Pascal

    2017-06-20

    To investigate the characteristics of the caregiving experience according to age at onset of dementia to adapt support programs. Fifty-seven spouse caregivers of persons with early-onset dementia (PEOD) and 93 spouse caregivers of persons with late-onset dementia (PLOD) participated. The characteristics of the caregiving experience were assessed using questionnaires. We compared the two groups according to age at onset of the disease using a multivariate test, Pillai's Trace test. The analysis showed that there were similarities and differences between the two groups of spouse caregivers. All spouse caregivers were confident in their caregiving role and fairly well prepared for future needs and reported mild depressive and anxious symptoms. However, they lacked informal support, had low confidence in requesting respite care and reported effects on their health. Compared to spouse caregivers of PLOD, spouse caregivers of PEOD had more severe perceptions of the cognitive disorders of persons with dementia (PWD) and had a better sense of preparedness and knowledge of services. Spouse caregivers of PLOD were more confident in their ability to control disturbing thoughts. The results suggest that programs should provide information on support networks to improve preparedness for spouse caregivers of PLOD as well as emphasizing positive coping strategies for caregivers of PEOD to maintain good-quality relationships with PWD, which influences the perception of the symptoms. For both groups, family relationships should be considered.

  8. Origin of frontal lobe spikes in the early onset benign occipital lobe epilepsy (Panayiotopoulos syndrome).

    Science.gov (United States)

    Leal, Alberto J R; Ferreira, José C; Dias, Ana I; Calado, Eulália

    2008-09-01

    Early onset benign occipital lobe epilepsy (Panayiotopoulos syndrome [PS]) is a common and easily recognizable epilepsy. Interictal EEG spike activity is often multifocal but most frequently localized in the occipital lobes. The origin and clinical significance of the extra-occipital spikes remain poorly understood. Three patients with the PS and interictal EEG spikes with frontal lobe topography were studied using high-resolution EEG. Independent component analysis (ICA) was used to decompose the spikes in components with distinct temporal dynamics. The components were mapped in the scalp with a spline-laplacian algorithm. The change in scalp potential topography from spike onset to peak, suggests the contribution of several intracranial generators, with different kinetics of activation and significant overlap. ICA was able to separate the major contributors to frontal spikes and consistently revealed an early activating group of components over the occipital areas in all the patients. The local origin of these early potentials was established by the spline-laplacian montage. Frontal spikes in PS are consistently associated with early and unilateral occipital lobe activation, suggesting a postero-anterior spike propagation. Frontal spikes in the PS represent a secondary activation triggered by occipital interictal discharges and do not represent an independent focus.

  9. Early-onset Alzheimer's disease: nonamnestic subtypes and type 2 AD.

    Science.gov (United States)

    Mendez, Mario F

    2012-11-01

    Patients with Alzheimer's disease (AD), the most prevalent neurodegenerative dementia, are usually elderly; however, ∼4-5% develop early-onset AD (EOAD) with onset before age 65. Most EOAD is sporadic, but about 5% of patients with EOAD have an autosomal dominant mutation such as Presenilin 1, Presenilin 2, or alterations in the Amyloid Precursor Protein gene. Although most Alzheimer's research has concentrated on older, late-onset AD (LOAD), there is much recent interest and research in EOAD. These recent studies indicate that EOAD is a heterogeneous disorder with significant differences from LOAD. From 22-64% of EOAD patients have a predominant nonamnestic syndrome presenting with deficits in language, visuospatial abilities, praxis, or other non-memory cognition. These nonamnestic patients may differ in several ways from the usual memory or amnestic patients. Patients with nonamnestic EOAD compared to typical amnestic AD have a more aggressive course, lack the apolipoprotein Eɛ4 (APOE ɛ4) susceptibility gene for AD, and have a focus and early involvement of non-hippocampal areas of brain, particularly parietal neocortex. These differences in the EOAD subtypes indicate differences in the underlying amyloid cascade, the prevailing pathophysiological theory for the development of AD. Together the results of recent studies suggest that nonamnestic subtypes of EOAD constitute a Type 2 AD distinct from the usual, typical disorder. In sum, the study of EOAD can reveal much about the clinical heterogeneity, predisposing factors, and neurobiology of this disease. Copyright © 2012 IMSS. Published by Elsevier Inc. All rights reserved.

  10. Early-onset Major Depressive Disorder in men is associated with childlessness.

    Science.gov (United States)

    Yates, William R; Meller, William H; Lund, Brian C; Thurber, Steve; Grambsch, Patricia L

    2010-07-01

    The self-reported number of children was compared for men and women from the National Epidemiologic Survey of Alcoholism and Related Conditions Survey (NESARC). Subjects with a diagnosis of major depressive disorder or bipolar disorder were compared to those without an axis I disorder. The effect of age, gender, marriage and diagnostic status on number of children was completed using multivariate analyses. Men with a history of major depressive disorder but not bipolar disorder reported higher rates of childlessness and lower mean number of children. This reduced number of children was related to an early age of onset of MDD. Thirty percent of men with an age of onset of MDD before 22 were childless compared to only 18.9% of men without an axis I disorder (Odds ratio=1.82, 95% CI=1.45-2.27). No effect of mood disorder on number of children was found in women with major depression or bipolar disorder. This study suggests that an early age of onset of major depressive disorder contributes to childlessness in men.

  11. Identifying anomalously early spring onsets in the CESM large ensemble project

    Science.gov (United States)

    Labe, Zachary; Ault, Toby; Zurita-Milla, Raul

    2017-06-01

    Seasonal transitions from winter to spring impact a wide variety of ecological and physical systems. While the effects of early springs across North America are widely documented, changes in their frequency and likelihood under the combined influences of climate change and natural variability are poorly understood. Extremely early springs, such as March 2012, can lead to severe economical losses and agricultural damage when these are followed by hard freeze events. Here we use the new Community Earth System Model Large Ensemble project and Extended Spring Indices to simulate historical and future spring onsets across the United States and in the particular the Great Lakes region. We found a marked increase in the frequency of March 2012-like springs by midcentury in addition to an overall trend towards earlier spring onsets, which nearly doubles that of observational records. However, changes in the date of last freeze do not occur at the same rate, therefore, causing a potential increase in the threat of plant tissue damage. Although large-scale climate modes, such as the Pacific Decadal Oscillation, have previously dominated decadal to multidecadal spring onset trends, our results indicate a decreased role in natural climate variability and hence a greater forced response by the end of the century for modulating trends. Without a major reduction in greenhouse gas emissions, our study suggests that years like 2012 in the US could become normal by mid-century.

  12. Association between polymorphisms in cancer-related genes and early onset of esophageal adenocarcinoma.

    Science.gov (United States)

    Wu, I-Chen; Zhao, Yang; Zhai, Rihong; Liu, Geoffrey; Ter-Minassian, Monica; Asomaning, Kofi; Su, Li; Liu, Chen-Yu; Chen, Feng; Kulke, Matthew H; Heist, Rebecca S; Christiani, David C

    2011-04-01

    There is an increasing incidence of esophageal adenocarcinoma (EA) among younger people in the western populations. However, the association between genetic polymorphisms and the age of EA onset is unclear. In this study, 1330 functional/tagging single-nucleotide polymorphisms (SNPs) from 354 cancer-related genes were genotyped in 335 white EA patients. Twenty important SNPs that have the highest importance scores and lowest classification error rate were identified by the random forest algorithm to be associated with early onset of EA (age ≤ 55 years). Subsequent logistic regression analysis indicated that 10 SNPs (rs2070744 of NOS3, rs720321 of BCL2, rs17757541 of BCL2, rs11775256 of TNFRSF10A, rs1035142 of CASP8, rs2236302 of MMP14, rs4740363 of ABL1, rs696217 of GHRL, rs2445762 of CYP19A1, and rs11941492 of VEGFR2/KDR) were significantly associated with early onset of EA (≤55 vs >55 years, all P polymorphisms in cancer-related genes, especially those in the apoptotic pathway, play an important role in the development of younger-aged EA in a dose-response manner.

  13. Maintaining Intestinal Health: The Genetics and Immunology of Very Early Onset Inflammatory Bowel DiseaseSummary

    Directory of Open Access Journals (Sweden)

    Judith R. Kelsen

    2015-09-01

    Full Text Available Inflammatory bowel disease (IBD is a multifactoral disease caused by dysregulated immune responses to commensal or pathogenic microbes in the intestine, resulting in chronic intestinal inflammation. An emerging population of patients with IBD younger than 5 years of age represent a unique form of disease, termed very early onset IBD (VEO-IBD, which is phenotypically and genetically distinct from older-onset IBD. VEO-IBD is associated with increased disease severity, aggressive progression, and poor responsiveness to most conventional therapies. Further investigation into the causes and pathogenesis of VEO-IBD will help improve treatment strategies and may lead to a better understanding of the mechanisms that are essential to maintain intestinal health or provoke the development of targeted therapeutic strategies to limit intestinal inflammation and promote tissue repair. Here, we discuss the phenotypic nature of VEO-IBD, the recent identification of novel gene variants associated with disease, and functional immunologic studies interrogating the contribution of specific genetic variants to the development of chronic intestinal inflammation. Keywords: Inflammatory Bowel Disease, Very Early Onset Inflammatory Bowel Disease, Whole Exome Sequencing, Mucosal Immunology

  14. Early Cannabis Use and Estimated Risk of Later Onset of Depression Spells : Epidemiologic Evidence From the Population-based World Health Organization World Mental Health Survey Initiative

    NARCIS (Netherlands)

    de Graaf, R.; Radovanovic, M.; van Laar, M.; Fairman, B.; Degenhardt, L.; Aguilar-Gaxiola, S.; Bruffaerts, R.; De Girolamo, G.; Fayyad, J.; Gureje, O.; Haro, J.M.; Huang, Y.Q.; Kostychenko, S.; Lepine, J.P.; Matschinger, H.; Mora, M.E.M.; Neumark, Y.; Ormel, J.; Posada-Villa, J.; Stein, D.J.; Tachimori, H.; Wells, J.E.; Anthony, J.C.

    2010-01-01

    Early-onset cannabis use is widespread in many countries and might cause later onset of depression. Sound epidemiologic data across countries are missing. The authors estimated the suspected causal association that links early-onset (age <17 years) cannabis use with later-onset (age >= 17 years)

  15. Attention-deficit/hyperactivity disorder in adolescence predicts onset of major depressive disorder through early adulthood.

    Science.gov (United States)

    Meinzer, Michael C; Lewinsohn, Peter M; Pettit, Jeremy W; Seeley, John R; Gau, Jeff M; Chronis-Tuscano, Andrea; Waxmonsky, James G

    2013-06-01

    The aim of this study was to examine the prospective relationship between a history of attention-deficit/hyperactivity disorder (ADHD) assessed in mid-adolescence and the onset of major depressive disorder (MDD) through early adulthood in a large school-based sample. A secondary aim was to examine whether this relationship was robust after accounting for comorbid psychopathology and psychosocial impairment. One thousand five hundred seven participants from the Oregon Adolescent Depression Project completed rating scales in adolescence and structured diagnostic interviews up to four times from adolescence to age 30. Adolescents with a lifetime history of ADHD were at significantly higher risk of MDD through early adulthood relative to those with no history of ADHD. ADHD remained a significant predictor of MDD after controlling for gender, lifetime history of other psychiatric disorders in adolescence, social and academic impairment in adolescence, stress and coping in adolescence, and new onset of other psychiatric disorders through early adulthood (hazard ratio, 1.81; 95% confidence interval, 1.04, 3.06). Additional significant, robust predictors of MDD included female gender, a lifetime history of an anxiety disorder, and poor coping skills in mid-adolescence, as well as the onset of anxiety, oppositional defiant disorder, and substance-use disorder after mid-adolescence. A history of ADHD in adolescence was associated with elevated risk of MDD through early adulthood and this relationship remained significant after controlling for psychosocial impairment in adolescence and co-occurring psychiatric disorders. Additional work is needed to identify the mechanisms of risk and to inform depression prevention programs for adolescents with ADHD. © 2013 Wiley Periodicals, Inc.

  16. Regional cerebral blood flow changes and neuropsychological functioning in early and late onset alcoholism

    International Nuclear Information System (INIS)

    Demir, B.; Ulug, B.; Ergun, E.; Erbas, B.

    2002-01-01

    Aim: Chronic alcoholism is strongly associated with morphologic and functional abnormalities in the brain. The age-of-onset of alcoholism symptoms might be of discriminating value and can be used to subdivide the population into more homogeneous groups. The aim of the study was to compare late and early onset alcoholism with regard to regional cerebral blood flow (rCBF) and neuropsychological functioning. Methods: Ten late onset (Type I) and thirteen early onset (Type II) male alcoholics were included in the study, the criterion being the age of onset for alcohol abuse. Six healthy, age-matched, male volunteers were included as a control group. rCBF changes were assessed using Tc-99m-HMPAO/SPECT after a detoxification period. Transaxial slices were assessed visually and semi quantitatively. Regional mean counts were divided to the mean counts of cerebellar and occipital regions to obtain semiquantitative ratios for superior frontal, middle frontal, inferior frontal, temporal and parietal lobes for the left and right hemispheres. The neuropsychological battery consisted of the Wisconsin Card Sorting Test, the Wechsler Memory Scale and the Word Fluency Test. Results: Type I and II groups had significantly asymmetric blood flow in the frontal region compared to control group (Left frontal percentage; Type I%46.8±2, Type II=48.3±2.3, Control=50.8±3, p=0.008). The semiquantitative ratios for the frontal subregions were lower for the patients compared to those of control group, however, statistically significant difference was observed only for the ratio of superior frontal region to occipital region in type I patients, for both left and right. The difference between the two subgroups was not statistically significant. Both groups of alcoholic patients also displayed impairment in frontal lobe functions and non-verbal memory. No significant difference was detected between the alcoholic subgroups on neuropsychological measures. There was no significant correlation

  17. Impulsivity in abstinent early- and late-onset alcoholics : differences in self-report measures and a discounting task

    NARCIS (Netherlands)

    Dom, G.; D'Haene, P.; Hulstijn, W.; Sabbe, B.G.C.

    2006-01-01

    Aims: To test the hypothesis that early-onset alcoholics (EOAs) can be differentiated from late-onset alcoholics (LOAs) by more severe substance-related problems and higher levels of impulsivity and aggression. Design and measurements: A cross-sectional patient survey with a community comparison

  18. Caregivers' perspectives on the pre-diagnostic period in early onset dementia: a long and winding road

    NARCIS (Netherlands)

    van Vliet, D.; de Vugt, M.E.; Bakker, C.; Koopmans, R.T.C.M.; Pijnenburg, Y.A.L.; Vernooij-Dassen, M.; Verhey, F.R.J.

    2011-01-01

    Background: Recognizing and diagnosing early onset dementia (EOD) can be complex and often takes longer than for late onset dementia. The objectives of this study are to investigate the barriers to diagnosis and to develop a typology of the diagnosis pathway for EOD caregivers. Methods:

  19. Early and late onset depression in young and middle aged adults : Differential symptomatology, characteristics and risk factors?

    NARCIS (Netherlands)

    Korten, Nicole C. M.; Comijs, Hannie C.; Lamers, Femke; Penninx, Brenda W. J. H.

    Background: Early onset depression (EOD) and late onset depression (LOD) may be different phenomena. In this study, differences between EOD and LOD in symptomatology, psychiatric characteristics and psychosocial/somatic factors were examined. Methods: Baseline data were from 1104 participants with a

  20. Psychiatric comorbidities of adults with early- and late-onset attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Lin, Yu-Ju; Yang, Li-Kuang; Gau, Susan Shur-Fen

    2016-06-01

    We evaluated the psychiatric comorbidities in adults who were diagnosed with Diagnostic and Statistical Manual of Mental disorders, 5th edition attention-deficit/hyperactivity disorder as a function of recalled symptom onset before and after the age of 7 years and whether the childhood attention-deficit/hyperactivity disorder symptoms were associated with psychiatric comorbidities. In all, 214 adults who were diagnosed with Diagnostic and Statistical Manual of Mental disorders, 5th edition attention-deficit/hyperactivity disorder and 174 non-attention-deficit/hyperactivity disorder controls (aged 17-40 years) received psychiatric interviews to confirm their previous and current attention-deficit/hyperactivity disorder status and other psychiatric diagnoses. Demographics and risks of lifetime psychiatric disorders were compared among three groups: (1) attention-deficit/hyperactivity disorder, onset attention-deficit/hyperactivity disorder, onset between 7 and 12 years (late-onset) and (3) non-attention-deficit/hyperactivity disorder controls. We also tested the effects of attention-deficit/hyperactivity disorder symptoms on the risk of later psychiatric comorbidities by Cox regression analyses. Regardless of the age of onset, attention-deficit/hyperactivity disorder was significantly associated with a wide range of psychiatric comorbidities. There were similar comorbid patterns between early- and late-onset attention-deficit/hyperactivity disorder. Regardless of attention-deficit/hyperactivity disorder diagnosis, increased severity of attention-deficit/hyperactivity disorder symptoms was associated with higher risks of oppositional defiant disorder, conduct disorder, dysthymia and sleep disorder but not major depression, which was associated with the attention-deficit/hyperactivity disorder diagnosis. Our findings suggest that elevating the threshold of age of onset to 12 years in Diagnostic and Statistical Manual of Mental disorders, 5th edition would not

  1. Early-onset restrictive eating disturbances in primary school boys and girls.

    Science.gov (United States)

    Kurz, Susanne; van Dyck, Zoé; Dremmel, Daniela; Munsch, Simone; Hilbert, Anja

    2015-07-01

    This study sought to determine the distribution of early-onset restrictive eating disturbances characteristic of the new DSM-5 diagnosis, avoidant/restrictive food intake disorder (ARFID) in middle childhood, as well as to evaluate the screening instrument, Eating Disturbances in Youth-Questionnaire (EDY-Q). A total of 1,444 8- to 13-year-old children were screened in regular schools (3rd to 6th grade) in Switzerland using the self-report measure EDY-Q, consisting of 12 items based on the DSM-5 criteria for ARFID. 46 children (3.2%) reported features of ARFID in the self-rating. Group differences were found for body mass index, with underweight children reporting features of ARFID more often than normal and overweight children. The EDY-Q revealed good psychometric properties, including adequate discriminant and convergent validity. Early-onset restrictive eating disturbances are commonly reported in middle childhood. Because of possible negative short- and long-term impact, early detection is essential. Further studies with structured interviews and parent reports are needed to confirm this study's findings.

  2. Early-onset alopecia and amyotrophic lateral sclerosis: a cohort study.

    Science.gov (United States)

    Fondell, Elinor; Fitzgerald, Kathryn C; Falcone, Guido J; O'Reilly, Eilis J; Ascherio, Alberto

    2013-10-01

    A recent meta-analysis of 7 genome-wide association studies on early balding (alopecia) revealed single nucleotide polymorphism variants in the region of the amyotrophic lateral sclerosis (ALS) gene TAR DNA-binding protein 43 (TARDBP/TDP-43). We therefore explored the association of early-onset alopecia and ALS in the Health Professionals Follow-up Study, a large cohort of 51,529 US men. In 1992, the participants (then aged 46-81 years) were asked to report their hair line pattern at age 45 years. During the follow-up period (1992-2008), 42 men were diagnosed with ALS. Of those, 13 had reported no alopecia, 18 had reported moderate alopecia, and 11 had reported extensive alopecia at age 45 years. Those who reported extensive alopecia had an almost 3-fold increased risk of ALS compared with those who reported no alopecia (relative risk = 2.74, 95% confidence interval: 1.23, 6.13). Furthermore, we observed a linear trend of increased risk of ALS with increasing level of balding at age 45 years (Ptrend = 0.02). In conclusion, men with early-onset alopecia seem to have a higher risk of ALS. The mechanisms underlying this association deserve further investigation.

  3. Phenotype-Genotype Analysis of Chinese Patients with Early-Onset LMNA-Related Muscular Dystrophy.

    Directory of Open Access Journals (Sweden)

    Dandan Tan

    Full Text Available This study aimed to analyze the correlation between the phenotype and genotype of Chinese patients with early-onset lamin A (LMNA-related muscular dystrophy (MD. The clinical and myopathological data of 21 Chinese pediatric patients with early-onset LMNA-related MD were collected and analyzed. LMNA gene mutation analysis was performed by direct sequencing of genomic DNA. Sublocalization of wild-type and mutant proteins were observed by immunofluorescence using cultured fibroblasts and human embryonic kidney 293 (HEK 293 cell. Seven patients were diagnosed with Emery-Dreifuss muscular dystrophy (EDMD and 14 were diagnosed with LMNA-associated congenital muscular dystrophy (L-CMD. Four biopsy specimens from the L-CMD cases exhibited inflammatory changes. Abnormal nuclear morphology was observed with both transmission electron microscopy and lamin A/C staining. We identified 10 novel and nine known LMNA gene mutations in the 21 patients. Some mutations (c.91G>A, c.94_96delAAG, c.116A>G, c.745C>T, c.746G>A, and c.1580G>C were well correlated with EDMD or L-CMD. LMNA-related MD has a common symptom triad of muscle weakness, joint contractures, and cardiac involvement, but the severity of symptoms and disease progression differ greatly. Inflammatory change in biopsied muscle is a characteristic of early-stage L-CMD. Phenotype-genotype analysis determines that some mutations are well correlated with LMNA-related MD.

  4. Thought and language disorders in very early onset schizophrenia, schizoaffective disorder and bipolar disorder

    Directory of Open Access Journals (Sweden)

    Telma Pantano

    Full Text Available Abstract Background Thought and language disorders are main features of adults with schizophrenia and bipolar disorders however studies on such abnormalities are scant in young patients with very early onset psychosis (VEOS. The aim of the present study is to assess the relationship between language and thought disorders in patients with very early onset schizophrenia (SCZ, schizoaffective disorders (SCA and bipolar disorders (BD. Method Forty-one patients (18 SCZ, 16 BD, and 7 SCA with mean age less than 15 years old were assessed through a series of neurocognitive and psycholinguistic tests, including the Thought, Language and Communication Scale (TLC. Results SCZ group performed worse in all tests as well as the TLC, followed by SCA and BD groups respectively. Thought disorders were related to deficits in executive functioning and semantic processing, and the metaphors’ test was the best predictor of TLC functioning. Discussion TD in SCZ, SCA and BD are one of the most important features in patients with VEOS and that the evaluation of metaphor comprehension can be an important instrument in the early detection of this disorder.

  5. Protective Low-Frequency Variants for Preeclampsia in the Fms Related Tyrosine Kinase 1 Gene in the Finnish Population.

    Science.gov (United States)

    Lokki, A Inkeri; Daly, Emma; Triebwasser, Michael; Kurki, Mitja I; Roberson, Elisha D O; Häppölä, Paavo; Auro, Kirsi; Perola, Markus; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Kivinen, Katja; Pouta, Anneli; Salmon, Jane E; Meri, Seppo; Daly, Mark; Atkinson, John P; Laivuori, Hannele

    2017-08-01

    Preeclampsia is a common pregnancy-specific vascular disorder characterized by new-onset hypertension and proteinuria during the second half of pregnancy. Predisposition to preeclampsia is in part heritable. It is associated with an increased risk of cardiovascular disease later in life. We have sequenced 124 candidate genes implicated in preeclampsia to pinpoint genetic variants contributing to predisposition to or protection from preeclampsia. First, targeted exomic sequencing was performed in 500 preeclamptic women and 190 controls from the FINNPEC cohort (Finnish Genetics of Preeclampsia Consortium). Then 122 women with a history of preeclampsia and 1905 parous women with no such history from the National FINRISK Study (a large Finnish population survey on risk factors of chronic, noncommunicable diseases) were included in the analyses. We tested 146 rare and low-frequency variants and found an excess (observed 13 versus expected 7.3) nominally associated with preeclampsia ( P preeclampsia. © 2017 American Heart Association, Inc.

  6. CDKL5 and ARX mutations are not responsible for early onset severe myoclonic epilepsy in infancy.

    Science.gov (United States)

    Nabbout, Rima; Depienne, Christel; Chipaux, Mathilde; Girard, Benoit; Souville, Isabelle; Trouillard, Oriane; Dulac, Olivier; Chelly, Jamel; Afenjar, Alexandra; Héron, Delphine; Leguern, Eric; Beldjord, Cherif; Bienvenu, Thierry; Bahi-Buisson, Nadia

    2009-11-01

    Severe myoclonic epilepsy of infancy (SMEI) or Dravet syndrome (DS) is a distinctive epilepsy syndrome often associated with de novo mutations in the SCN1A gene. However, 25-30% patients with SMEI/DS are negative for SCN1A mutation screening, suggesting that other molecular mechanisms may account for these disorders. Given the overlapping and heterogeneous clinical features of CDKL5- and ARX-related epilepsies and SMEI/DS, we postulated that CDKL5 mutations in females and ARX mutations gene in males may be associated with early onset seizures forms of SMEI/DS. Twenty-eight patients with early onset SMEI/DS before 6 months negative for SCN1A mutational screening were selected and screened for mutations in the ARX gene in males (n=14) or the CDKL5 gene in females (n=14). No mutations in either gene were found except one intronic variation of uncertain pathogenicity in the CDKL5 gene. All patients started seizures at mean age of 3.48 months. Thirteen patients had familial history of epilepsy or febrile seizures. Patients evolved toward refractory epilepsy with generalized tonic clonic seizures (18/28) and myoclonia (23/28) and severe neurological impairment with autistic features (13/28), ataxia (14/28) and spasticity (5/28). No patient ever exhibited infantile spasms, dystonia, or Rett-like features. Our results illustrate that mutation screening of ARX and CDKL5 is not effective in patients selected on the basis of clinical signs associated to early onset SMEI/DS. In addition, they might reflect that other phenotypic features associated with CDKL5 mutations (Rett-like features, infantile spasm) or ARX mutations (dystonia, spasticity) are more distinctive. 2009 Elsevier B.V. All rights reserved.

  7. [A case of Neuro-Behçet's disease with early onset of bipolar mood disorder].

    Science.gov (United States)

    Nakano, Yuko; Hatanaka, Yuki; Ikebuchi, Emi; Shimizu, Teruo; Nanko, Shinichiro; Utsumii, Takeshi

    2004-01-01

    In this report, we describe a case of Neuro-Behçet's disease with early onset of bipolar mood disorder. A 53-year-old man with neuropathy including dysphasia and dyslalia developed bipolar mood disorder with anxiety, agitation, depressive mood, talkativeness, hyperkinesias, and appetite rise, and soon exhibited severe personality deterioration. Oral aphthae, cell proliferation and elevated IL-6 levels in spinal fluid, and the patient's clinical downhill course with remission and relapse in spite of good reaction to steroid preparation indicated the possibility of Neuro-Behçet's disease. Brain MRI showed clear swelling of the brain stem area, especially in the pons, in the active phase with low signal in T1-weighted images contrasting with clear high signal in T2-weighted images and FLAIR. At the time of remission, atrophy of the brain stem was shown. These findings were consistent with the view reported in recent years concerning the brain image of Neuro-Behçet's disease, which seemed to be useful for the differential diagnosis. This case manifested two outstanding clinical features. First, it showed bipolar mood swing or mixed state distinguishable from disinhibition or euphoria in deteriorated personality, which is common in this condition. A clear bipolar mood disorder has not been described until now in Neuro-Behçet's disease. Second, subclinical dysthymia or hypomanic phase occurred before clear onset of the disease. In Neuro-Behçet's disease, it is currently considered that psychiatric symptoms may appear in the early stage, but there is controversy as to whether they can precede the other symptoms. Our case indicated very early onset of psychiatric symptoms in this condition.

  8. Bone Characteristics and Their Determinants in Adolescents and Young Adults with Early-Onset Severe Obesity.

    Science.gov (United States)

    Viljakainen, H T; Valta, H; Lipsanen-Nyman, M; Saukkonen, T; Kajantie, E; Andersson, S; Mäkitie, O

    2015-10-01

    Childhood obesity is associated with compromised bone health. We studied bone characteristics and their determinants in obese young adults. The study included 68 subjects with early-onset severe obesity and 73 normal-weight controls. Data on physical activity (PA), diet and smoking were collected. Bone characteristics were measured using peripheral QCT. The obese and control subjects were similar in age (mean 19.6 ± 2.6 years) and height but BMIs differed (39.7 and 22.6 kg/m(2)). A clustering of unhealthy lifestyles was marked: Obese subjects reported less supervised PA in childhood, adolescence and currently (p obese women, all crude bone characteristics were higher than in controls; in men, the differences were smaller. Associations of lifestyle factors with bone characteristics were tested using partial correlations. Independently of BMI, supervised PA in adolescence and alcohol consumption were related positively to bone characteristics in both groups. HEI associated positively with bone characteristics only in controls, while smoking was a positive determinant of bone characteristics only in obese subjects. The multivariate model showed that the contribution of lifestyle factors to bone characteristics was minimal compared with BMI. Early-onset obesity is accompanied by poor dietary quality, sedentary lifestyle, and more frequent smoking, but the overall contribution of these lifestyle factors to bone strength is limited. Bone strength is more likely to be compromised in men and in unloaded bone sites in subjects with early-onset severe obesity. The impact of obesity-related endocrine changes on bone characteristics need to be evaluated in future studies.

  9. Screening of KCNN3 in patients with early-onset lone atrial fibrillation

    DEFF Research Database (Denmark)

    Olesen, Morten Sig; Jabbari, Javad; Holst, Anders G

    2011-01-01

    -nucleotide polymorphism (SNP) in KCNN3 with lone AF. Methods and results We sequenced the coding region and splice junctions of KCNN3 in 209 early-onset lone AF patients, screening for variations. A group of 208 healthy blood donors with normal ECGs and without cardiac symptoms were used as controls. All patients...... and controls were of Danish ethnicity. No mutations were found in the coding regions or splice sites of KCNN3. We found one known exonic synonymous SNP (rs1131820) in KCNN3 that was associated with AF. Both the genotype distribution and allele frequencies of SNP rs1131820 were significantly different between...

  10. Early-Onset Bipolar Disorder: Characteristics and Outcomes in the Clinic.

    Science.gov (United States)

    Connor, Daniel F; Ford, Julian D; Pearson, Geraldine S; Scranton, Victoria L; Dusad, Asha

    2017-12-01

    To assess patient characteristics and clinician-rated outcomes for children diagnosed with early-onset bipolar disorder in comparison to a depressive disorders cohort from a single clinic site. To assess predictors of bipolar treatment response. Medical records from 714 consecutive pediatric patients evaluated and treated at an academic tertiary child and adolescent psychiatry clinic between 2006 and 2012 were reviewed. Charts of bipolar children (n = 49) and children with depressive disorders (n = 58) meeting study inclusion/exclusion criteria were compared on variables assessing clinical characteristics, treatments, and outcomes. Outcomes were assessed by using pre- and post-Clinical Global Impressions (CGI)-Severity and Children's Global Assessment Scale (CGAS) scores, and a CGI-Improvement score ≤2 at final visit determined responder status. Bipolar outcome predictors were assessed by using multiple linear regression. Clinic prevalence rates were 6.9% for early-onset bipolar disorder and 1.5% for very early-onset bipolar disorder. High rates of comorbid diagnoses, symptom severity, parental stress, and child high-risk behaviors were found in both groups. The bipolar cohort had higher rates of aggression and higher lifetime systems of care utilization. The final CGI and CGAS outcomes for unipolar depression patients differed statistically significantly from those for the bipolar cohort, reflecting better clinical status and more improvement at outcome for the depression patients. Both parent-reported Child Behavior Checklist total T-score at clinic admission and the number of lifetime systems-of-care for the child were significantly and inversely associated with improvement for the bipolar cohort. Early-onset bipolar disorder is a complex and heterogeneous psychiatric disorder. Evidence-based treatment should emphasize psychopharmacology with adjunctive family and individual psychotherapy. Strategies to improve engagement in treatment may be especially

  11. Parental and Child Characteristics Related to Early-Onset Disordered Eating

    DEFF Research Database (Denmark)

    Larsen, Pernille Stemann; Strandberg-Larsen, Katrine; Micali, Nadia

    2015-01-01

    the following: higher body weight, previously reported disordered eating, body dissatisfaction, depression, parental disordered eating, and parental comments/concerns about child's weight and eating. The findings were inconsistent for sex, age, socioeconomic status, ethnicity, self-esteem/worth, and parental......-four studies fit these criteria. Most studies were based on community samples with a cross-sectional design. The included studies varied considerably in size, instruments used to assess early-onset disordered eating, and parental and child characteristics investigated. Important determinants included...

  12. Apolipoprotein E Allelic Frequency Altered in Women with Early-onset Breast Cancer

    Directory of Open Access Journals (Sweden)

    Tirtsa Porrata-Doria

    2010-01-01

    Full Text Available Among women, the most prevalent type of cancer is breast cancer, affecting 1 out of every 8 women in the United States; in Puerto Rico, 70 out of every 100,000 will develop some type of breast cancer. Therefore, a better understanding of the potential risk factors for breast cancer could lead to the development of early detection tools. A gene that has been proposed as a risk factor in several populations around the world is Apolipoprotein E (apoE. ApoE functions as a mechanism of transport for lipoproteins and cholesterol throughout the body, with 3 main isoforms present in humans (apoE2, apoE3, and apoE4. Whether or not apoE4 is a risk factor for breast cancer remains controversial. Previous studies have either included test subjects of all ages (20–80 or have focused on late-onset (after age 50 breast cancer; none has concentrated specifically on early-onset (aged 50 and younger breast cancer. The objectives of this study was to examine (in a Puerto Rican population the differences in the relative frequency of occurrence of apoE4 in non-breast cancer versus breast cancer patients and to examine, as well, the potential differences of same in early- versus late-onset patients. We found an increased frequency of apoE4 (odds ratio 2.15 only in early-onset breast cancer survivors, which is similar to the findings of those studies that combined or adjusted for age as well as for an association between apoE4 and decreased tumor size. ApoE is also a potential risk factor for long-term cognitive effects after chemotherapy and affects response to hormone replacement. Our data supports the theory that knowing the apoE genotype of women who are at risk of developing breast cancer may be beneficial, as such knowledge would aid in the prediction of tumor size and the development of treatment regimens.

  13. Mitochondrial Myopathy: A Rare Cause of Early-Onset Vocal Fold Atrophy

    Science.gov (United States)

    Kelly, Elizabeth A.; Bock, Jonathan M.; Peltier, Amanda C.; Oh, Shin J.; Garrett, C. Gaelyn

    2014-01-01

    Objectives We present the second published case of laryngeal involvement in mitochondrial myopathy. Methods A patient with laryngeal involvement of mitochondrial myopathy is presented, together with a literature review. Results A 41-year-old man presented with progressive breathy dysphonia. His brother had mitochondrial myopathy. Biopsy of the biceps muscle demonstrated cytochrome C oxidase–negative ragged blue fibers confirming mitochondrial myopathy. Videostroboscopy showed marked vocal fold atrophy, but subsequent injection laryngoplasty did not significantly improve the patient’s voice, despite improved postoperative glottic closure. Conclusions Mitochondrial myopathy should be considered in the differential diagnosis of severe early-onset vocal fold atrophy. PMID:23577570

  14. Management of early onset neonatal sepsis differs in the north and south of Scandinavia

    DEFF Research Database (Denmark)

    Drageset, Martin; Fjalstad, Jon Widding; Mortensen, Sven

    2017-01-01

    AIM: This study compared the management and outcomes of early-onset neonatal sepsis (EONS) in two tertiary neonatal units in Denmark and Norway. METHODS: We retrospectively studied all infants diagnosed with EONS between April 2010 and March 2013 and managed at Odense University Hospital, Denmark...... blood cultures had higher C-reactive protein levels than patients with negative blood cultures and higher sepsis-attributable mortality. Lumbar punctures were performed more frequently in Denmark. CONCLUSION: There were marginal differences in the management of EONS between units in Denmark and Norway...

  15. Experimental and Clinical Studies of Oxidative Stress in Pre-Eclampsia

    OpenAIRE

    Nash, Peppi

    2007-01-01

    Impaired placentation and oxidative stress are proposed to play major roles in the pathogenesis of pre-eclampsia (PE). It has recently been pointed out that PE might be more than one disease and may have several different pathogeneses. This thesis describes a new animal model for PE and examines the role of oxidative stress in early respective late onset PE. The effects of Suramin injections on day 10 and 11 of pregnancy were investigated in normal and diabetic rats of two strains (U and H), ...

  16. Early- and late-onset Alzheimer disease: Are they the same entity?

    Science.gov (United States)

    Tellechea, P; Pujol, N; Esteve-Belloch, P; Echeveste, B; García-Eulate, M R; Arbizu, J; Riverol, M

    2018-05-01

    Early-onset Alzheimer disease (EOAD), which presents in patients younger than 65 years, has frequently been described as having different features from those of late-onset Alzheimer disease (LOAD). This review analyses the most recent studies comparing the clinical presentation and neuropsychological, neuropathological, genetic, and neuroimaging findings of both types in order to determine whether EOAD and LOAD are different entities or distinct forms of the same entity. We observed consistent differences between clinical findings in EOAD and in LOAD. Fundamentally, the onset of EOAD is more likely to be marked by atypical symptoms, and cognitive assessments point to poorer executive and visuospatial functioning and praxis with less marked memory impairment. Alzheimer-type features will be more dense and widespread in neuropathology studies, with structural and functional neuroimaging showing greater and more diffuse atrophy extending to neocortical areas (especially the precuneus). In conclusion, available evidence suggests that EOAD and LOAD are 2 different forms of a single entity. LOAD is likely to be influenced by ageing-related processes. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Late Onset Postpartum Eclampsia: It is Really Never Too Late—A Case of Eclampsia 8 Weeks after Delivery

    Directory of Open Access Journals (Sweden)

    Jens Minnerup

    2010-01-01

    Full Text Available Introduction. Eclampsia is the combination of preeclampsia and seizures. Approximately one-half of all cases of eclampsia occur postpartum. Thereby late onset postpartum eclampsia is defined by its onset more than 48 hours after delivery. Summary of Case. We report a postpartum eclampsia occurring 8 weeks after delivery, which is the latest onset ever described. The course was complicated by an intracerebral hemorrhage (ICH. Conclusion. A late onset postpartum eclampsia even several weeks after delivery should be considered as possible diagnosis, since early treatment initiation with magnesium sulphate and antihypertensive medication prevents severe complications and reduces mortality.

  18. Characterization of the onset of embryonic control and early development in the bovine embryo

    International Nuclear Information System (INIS)

    Barnes, F.L.

    1988-01-01

    Bovine embryos were used to determine if morphological and molecular features of early development are similar to in vivo recovered bovine embryos and to determine at what level early bovine development is regulated. Radiolabeling of IVP embryos and in vivo recovered embryos with 35 S-methionine for SDS-polyacrylamide gel electrophoresis reveals that these embryos are equivalent. Few differences in protein profiles are observed between 1- and early 4-cell embryos. A change in protein profiles begins at the mid 4-cell stage and continues into the 8-cell stage. Few differences in protein profiles are observed between 1- and early 4-cell embryos. A change in protein profiles begins at the mid 4-cell stage and continues into the 8-cell stage. Few differences in protein profiles are observed between late 8-cells and morulae. This transition is α-amanitin sensitive therefore due to de novo embryonic transcription. Embryonic transcription is partially responsible for terminating the post-transcriptionally regulated period of early bovine development. Argentophillic nucleolar organizing regions (Ag-NORs) indicate onset of nucleolar activation. Ag-NORs were absent in 2- and 4-cell IVP embryos and rarely occurred in 8-cell IVP embryos cultured in vitro. IVP 1- and 2-cell embryos cultured to blastocysts in sheep oviducts demonstrated Ag-NORs. Thus the lack of nucleolar activation of IVP embryos cultured in vitro is culture induced between the 2- and 8-cell stage

  19. Preeclampsia: long-term consequences for vascular health

    Directory of Open Access Journals (Sweden)

    Amaral LM

    2015-07-01

    Full Text Available Lorena M Amaral, Mark W Cunningham Jr, Denise C Cornelius, Babbette LaMarca Department of Pharmacology, University of Mississippi Medical Center, Jackson, MS, USA Abstract: Preeclampsia (PE is a pregnancy-specific syndrome and one of the leading causes of preterm birth, neonatal and maternal morbidity and mortality. This disease is characterized by new onset hypertension usually in the third trimester of pregnancy and is sometimes associated with proteinuria, although proteinuria is not a requirement for the diagnosis of PE. In developing countries, women have a higher risk of death due to PE than more affluent countries and one of the most frequent causes of death is high blood pressure and stroke. Although PE only affects approximately 2%–8% of pregnancies worldwide it is associated with severe complications such as eclampsia, hemorrhagic stroke, hemolysis, elevated liver enzymes and low platelets (HELLP syndrome, renal failure and pulmonary edema. Importantly, there is no “cure” for the disease except for early delivery of the baby and placenta, leaving PE a health care risk for babies born from PE moms. In addition, PE is linked to the development of cardiovascular disease and stroke in women after reproductive age, leaving PE a risk factor for long-term health in women. This review will highlight factors implicated in the pathophysiology of PE that may contribute to long-term effects in women with preeclamptic pregnancies. Keywords: preeclampsia, endothelial dysfunction, AT1-AA, CD4+ T helper cells

  20. A case of probable non-familial early onset Alzheimer dementia in a Hispanic male

    Directory of Open Access Journals (Sweden)

    Corey Ephrussi

    2012-07-01

    Full Text Available Background: Early onset Alzheimer's type dementia (EOAD is usually familial and associated with mutations in the Presenilin-1 (PSEN1, Presenilin-2 (PSEN2 or amyloid precursor protein (APP genes. It is rarely reported in patients of Hispanic descent. Case report: A 49-year-old Hispanic male developed significant cognitive impairment over a 4-year period. PET scan showed diminished metabolic activity in the posterior parietal/temporal lobes. Genetic testing revealed the presence of a PSEN1 gene mutation. Conclusion: Disparities in health care may account for an under-recognition of EOAD in the Hispanic population. Clinicians should test for EOAD in all patients with appropriate symptomatology, regardless of ethnicity. Early recognition and enrollment in clinical trials is vital to enhancing our understanding of the natural history and treatment of this condition.

  1. Neuropsychological functioning in early-onset first-episode psychosis: comparison of diagnostic subgroups.

    Science.gov (United States)

    Zabala, Arantzazu; Rapado, Marta; Arango, Celso; Robles, Olalla; de la Serna, Elena; González, Cristina; Rodríguez-Sánchez, José Manuel; Andrés, Patricia; Mayoral, María; Bombín, Igor

    2010-04-01

    The aims of this study were to examine the nature and extent of cognitive impairment in first-episode early-onset psychosis (FE-EOP) soon after their stabilisation and to search for potential differences according to specific diagnostic sub-groups of patients. As part of a Spanish multicentre longitudinal study, 107 FE-EOP patients and 98 healthy controls were assessed on the following cognitive domains: attention, working memory, executive functioning, and verbal learning and memory. Three diagnostic categories were established in the patient sample: schizophrenia (n = 36), bipolar disorder (n = 19), and other psychosis (n = 52). Patients performed significantly worse than controls in all cognitive domains. The three diagnostic sub-groups did not differ in terms of impaired/preserved cognitive functions or degree of impairment. FE-EOP patients show significant cognitive impairment that, during this early phase, seems to be non-specific to differential diagnosis.

  2. Early-onset heroin use and its link to conduct disorder: Clinical and management challenges

    Directory of Open Access Journals (Sweden)

    Shobhit Jain

    2016-01-01

    Full Text Available Childhood substance abuse and delinquency often progress to harder substances and antisocial personality disorder and carries deleterious consequences for self, family and community at large. Early management of such cases poses several clinical and management challenges, as highlighted in the present case. The treatment seeking for this sub-population is very low in spite of community surveys showing a worrisome pattern of substance use among younger population. Further, very few specialty clinics and trained manpower exist in the country to manage early onset substance use. Whether conduct disorder be cause or consequence for drug use is debatable, in view of shared risk factors. The present case helps to understand need for comprehensive assessment for identifying risk factors and comorbid conditions. Only pharmacological management does not help, psychosocial management must be delivered. Several prevention strategies may also help if these risk factors are identified before progression to illicit substance use disorder.

  3. Biallelic Loss of Function of SORL1 in an Early Onset Alzheimer's Disease Patient.

    Science.gov (United States)

    Le Guennec, Kilan; Tubeuf, Hélène; Hannequin, Didier; Wallon, David; Quenez, Olivier; Rousseau, Stéphane; Richard, Anne-Claire; Deleuze, Jean-François; Boland, Anne; Frebourg, Thierry; Gaildrat, Pascaline; Campion, Dominique; Martins, Alexandra; Nicolas, Gaël

    2018-01-01

    Heterozygous SORL1 protein truncating variants (PTV) are a strong risk factor for early-onset Alzheimer's disease (EOAD). In case control studies performed at the genome-wide level, PTV definition is usually straightforward. Regarding splice site variants, only those affecting canonical sites are typically included. Some other variants, not annotated as PTV, could, however, affect splicing and hence result in a loss of SORL1 function. We took advantage of the whole exome sequencing data from the 9/484 patients with a previously reported SORL1 PTV in the French EOAD series and searched for a second variant which may affect splicing and eventually result in more than 50% loss of function overall. We found that one patient, known to carry a variant predicted to disrupt the canonical 5' splice site of exon 8, also carried a second novel intronic variant predicted to affect SORL1 splicing of exon 29. Segregation analysis showed that the second variant was located in trans from the known PTV. We performed ex vivo minigene splicing assays and showed that both variants led to the generation of transcripts containing a premature stop codon. This is therefore the first evidence of a human carrying biallelic SORL1 PTV. This patient had a family history of dementia in both maternal and paternal lineages with later ages of onset than the proband himself. However, his 55 years age at onset was in the same ranges as previously published SORL1 heterozygous PTV carriers. This suggests that biallelic loss of SORL1 function is an extremely rare event that was not associated with a dramatically earlier age at onset than heterozygous SORL1 loss-of-function variant carriers, in this single patient.

  4. Preeclampsia and High Blood Pressure During Pregnancy

    Science.gov (United States)

    ... Gynecologists f AQ FREQUENTLY ASKED QUESTIONS FAQ034 PREGNANCY Preeclampsia and High Blood Pressure During Pregnancy • What is ... is chronic hypertension during pregnancy managed? • What is preeclampsia? • When does preeclampsia occur? • What causes preeclampsia? • What ...

  5. Early functional and morphological brain disturbances in late-onset intrauterine growth restriction.

    Science.gov (United States)

    Starčević, Mirta; Predojević, Maja; Butorac, Dražan; Tumbri, Jasna; Konjevoda, Paško; Kadić, Aida Salihagić

    2016-02-01

    To determine whether the brain disturbances develop in late-onset intrauterine growth restriction (IUGR) before blood flow redistribution towards the fetal brain (detected by Doppler measurements in the middle cerebral artery and umbilical artery). Further, to evaluate predictive values of Doppler arterial indices and umbilical cord blood gases and pH for early functional and/or morphological brain disturbances in late-onset IUGR. This cohort study included 60 singleton term pregnancies with placental insufficiency caused late-onset IUGR (IUGR occurring after 34 gestational weeks). Umbilical artery resistance index (URI), middle cerebral artery resistance index (CRI), and cerebroumbilical (C/U) ratio (CRI/URI) were monitored once weekly. Umbilical blood cord samples (arterial and venous) were collected for the analysis of pO2, pCO2 and pH. Morphological neurological outcome was evaluated by cranial ultrasound (cUS), whereas functional neurological outcome by Amiel-Tison Neurological Assessment at Term (ATNAT). 50 fetuses had C/U ratio>1, and 10 had C/U ratio≤1; among these 10 fetuses, 9 had abnormal neonatal cUS findings and all 10 had non-optimal ATNAT. However, the total number of abnormal neurological findings was much higher. 32 neonates had abnormal cUS (53.37%), and 42 (70.00%) had non-optimal ATNAT. Furthermore, Doppler indices had higher predictive validity for early brain disturbances than umbilical cord blood gases and pH. C/U ratio had the highest predictive validity with threshold for adverse neurological outcome at value 1.13 (ROC analysis), i.e., 1.18 (party machine learning algorithm). Adverse neurological outcome at average values of C/U ratios>1 confirmed that early functional and/or structural brain disturbances in late-onset IUGR develop even before activation of fetal cardiovascular compensatory mechanisms, i.e., before Doppler signs of blood flow redistribution between the fetal brain and the placenta. Copyright © 2015 Elsevier Ireland Ltd

  6. Neuropsychological evidence for abnormal neurodevelopment associated with early-onset psychoses.

    Science.gov (United States)

    Bombin, I; Mayoral, M; Castro-Fornieles, J; Gonzalez-Pinto, A; de la Serna, E; Rapado-Castro, M; Barbeito, S; Parellada, M; Baeza, I; Graell, M; Payá, B; Arango, C

    2013-04-01

    The longitudinal neuropsychological study of first-episode early-onset psychosis (EOP) patients, whose brain maturation is still in progress at the time of illness onset, provides a unique opportunity to compare their cognitive development with that of healthy subjects, in search of specific patterns resulting from the interaction between neurodevelopmental processes and the presence of psychotic disorders. Method Seventy-five first-episode EOP patients (schizophrenia n = 35; bipolar disorder n = 17; other forms of psychosis n = 23) with a mean age of 15.53 years were assessed with a neuropsychological battery that included measures of attention, working memory, memory and executive functions within 6 months following the onset of the first psychotic symptom (baseline) and 2 years later. Psychotic symptoms were assessed at both times with the Positive and Negative Symptom Scale (PANSS). Seventy-nine healthy subjects matched for age and education served as controls. EOP patients showed significant cognitive impairment at both baseline and the 2-year follow-up, with no significant differences between diagnostic groups at either time. Both healthy controls and EOP patients improved in all cognitive measures, except for patient working memory. Improvement in patient attention lost significance after controlling for psychotic symptom reduction. No significant time/diagnosis interaction was found among patients (p > 0.405). Cognitive impairment in EOP is already present at the first episode, and cognitive development seems to be arrested early in EOP patients compared to their healthy peers, at least for some cognitive functions. These and previous similar results support the neurodevelopmental hypothesis of psychosis.

  7. Focused Molding Using Adhesive Pads in Mehta Casting for Early-Onset Scoliosis.

    Science.gov (United States)

    Abraham, Roby; Sponseller, Paul D

    2014-11-01

    Prospective clinical series. To determine the effect of adhesive pads placed over the apex of scoliosis curves on curve correction 1) after the first cast and 2) after the final cast. Early-onset scoliosis is often effectively managed by serial casting. Properly localizing the apex of the molds with the cast in place is challenging. The authors explored the effectiveness of a novel technique: incorporation of adhesive pads placed over the major curve apex before Mehta casting. The 27 patients who received body casts (2000-2013) were divided into 2 groups: those without and with apical adhesive pads (5-6 layers of pads placed on the major curve's apex during casting): non-pad (NP) group (n = 12) and pad (P) group (n = 15), respectively. Groups were compared regarding the percentage of Cobb angle change from the first cast and curve correction to a Cobb angle of cast curve correction was 39% ± 18% and 56% ± 17% in the NP and P groups, respectively. Of the 26 patients out of a cast, 11 (42%) had a Cobb angle of casting were effective in increasing the amount of major curve correction from the first cast for idiopathic early-onset scoliosis and in decreasing curves to <25° at final follow-up. Copyright © 2014 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.

  8. Serial elongation-derotation-flexion casting for children with early-onset scoliosis.

    Science.gov (United States)

    Canavese, Federico; Samba, Antoine; Dimeglio, Alain; Mansour, Mounira; Rousset, Marie

    2015-12-18

    Various early-onset spinal deformities, particularly infantile and juvenile scoliosis (JS), still pose challenges to pediatric orthopedic surgeons. The ideal treatment of these deformities has yet to emerge, as both clinicians and surgeons still face multiple challenges including preservation of thoracic motion, spine and cage, and protection of cardiac and lung growth and function. Elongation-derotation-flexion (EDF) casting is a technique that uses a custom-made thoracolumbar cast based on a three-dimensional correction concept. EDF can control progression of the deformity and - in some cases-coax the initially-curved spine to grow straighter by acting simultaneously in the frontal, sagittal and coronal planes. Here we provide a comprehensive review of how infantile and JS can affect normal spine and thorax and how serial EDF casting can be used to manage these spinal deformities. A fresh review of the literature helps fully understand the principles of the serial EDF casting technique and the effectiveness of conservative treatment in patients with early-onset spinal deformities, particularly infantile and juvenile scolisois.

  9. Diagnosing early onset dementia and then what? A frustrating system of aftercare resources

    Directory of Open Access Journals (Sweden)

    Chemali Z

    2012-01-01

    Full Text Available Z Chemali1–3, S Schamber2, EC Tarbi2, D Acar1,2, M Avila-Urizar21Harvard Medical School, 2Departments of Neurology and Psychiatry, Division of Cognitive and Behavioral Neurology, Brigham and Women’s Hospital, 3Departments of Psychiatry and Neurology, Massachusetts General Hospital, Boston, MA, USAAbstract: Recent studies indicate that the prevalence of early onset dementia (EOD is more common than it was once presumed. As such, and considering the substantial challenges EOD presents to the patient, caregivers, and health care providers, this study sought to investigate the mechanism of care delivered to these patients. A medical record chart review was conducted for 85 patients attending a memory disorder unit who initially presented to rule out EOD as a working diagnosis. The results suggest that while the majority of these patients received an extensive work-up and were heavily medicated, they remained at home, where they lacked adequate age-related services and could not be placed, despite the crippling caregiver burden. This manuscript is a platform to discuss our current system limitations in the care of these patients with an eye on new opportunities for this challenging group.Keywords: early onset dementia, social work, services, caregiving

  10. Early-Onset Central Diabetes Insipidus due to Compound Heterozygosity for AVP Mutations.

    Science.gov (United States)

    Bourdet, Karine; Vallette, Sophie; Deladoëy, Johnny; Van Vliet, Guy

    2016-01-01

    Genetic cases of isolated central diabetes insipidus are rare, are mostly due to dominant AVP mutations and have a delayed onset of symptoms. Only 3 consanguineous pedigrees with a recessive form have been published. A boy with a negative family history presented polyuria and failure to thrive in the first months of life and was diagnosed with central diabetes insipidus. Magnetic resonance imaging showed a normal posterior pituitary signal. A molecular genetic analysis of the AVP gene showed that he had inherited a previously reported mutation from his Lebanese father and a novel A>G transition in the splice acceptor site of intron 1 (IVS1-2A>G) from his French-Canadian mother. Replacement therapy resulted in the immediate disappearance of symptoms and in weight gain. The early polyuria in recessive central diabetes insipidus contrasts with the delayed presentation in patients with monoallelic AVP mutations. This diagnosis needs to be considered in infants with very early onset of polyuria-polydipsia and no brain malformation, even if there is no consanguinity and regardless of whether the posterior pituitary is visible or not on imaging. In addition to informing family counseling, making a molecular diagnosis eliminates the need for repeated imaging studies. © 2015 S. Karger AG, Basel.

  11. Impact of substance use on the onset and course of early psychosis.

    Science.gov (United States)

    Verdoux, Hélène; Tournier, Marie; Cougnard, Audrey

    2005-11-01

    The strong comorbidity between psychosis and substance use is already identifiable in early psychosis, raising the question of the direction of the association between substance use and psychosis onset. It has long been considered that this association was explained by the self-medication hypothesis. This hypothesis has been recently challenged by several prospective studies carried out in population-based samples, showing a dose-response relationship between cannabis exposure and risk of psychosis. This association was independent from potential confounding factors such as exposure to other drugs and pre-existence of psychotic symptoms. As a large percentage of subjects from the general population is now exposed to this drug, even a small increase in the risk of adverse effects may have significant deleterious consequences for the health of the population. Hence, reducing exposure to cannabis may contribute to prevention of some incident cases of psychosis. Regarding prognosis, persistent substance misuse after the onset of psychosis has a deleterious impact on clinical outcome. Therapeutic programs for subjects with dual diagnosis should be implemented early in the course of psychosis to maximise their impact on the course of illness.

  12. Germline Mutations of Inhibins in Early-Onset Ovarian Epithelial Tumors

    Science.gov (United States)

    Tournier, Isabelle; Marlin, Régine; Walton, Kelly; Charbonnier, Françoise; Coutant, Sophie; Théry, Jean-Christophe; Charbonnier, Camille; Spurrell, Cailyn; Vezain, Myriam; Ippolito, Lorena; Bougeard, Gaëlle; Roman, Horace; Tinat, Julie; Sabourin, Jean-Christophe; Stoppa-Lyonnet, Dominique; Caron, Olivier; Bressac-de Paillerets, Brigitte; Vaur, Dominique; King, Mary-Claire; Harrison, Craig; Frebourg, Thierry

    2014-01-01

    To identify novel genetic bases of early-onset epithelial ovarian tumors, we used the trio exome sequencing strategy in a patient without familial history of cancer who presented metastatic serous ovarian adenocarcinomas at 21 years of age. We identified a single de novo mutation (c.1157A>G/p.Asn386Ser) within the INHBA gene encoding the βA-subunit of inhibins/activins, which play a key role in ovarian development. In vitro, this mutation alters the ratio of secreted activins and inhibins. In a second patient with early-onset serous borderline papillary cystadenoma, we identified an unreported germline mutation (c.179G>T/p.Arg60Leu) of the INHA gene encoding the α-subunit, the partner of the βA-subunit. This mutation also alters the secreted activin/inhibin ratio, by disrupting both inhibin A and inhibin B biosynthesis. In a cohort of 62 cases, we detected an additional unreported germline mutation of the INHBA gene (c.839G>A/p.Gly280Glu). Our results strongly suggest that inhibin mutations contribute to the genetic determinism of epithelial ovarian tumors. PMID:24302632

  13. GATA2 is associated with familial early-onset coronary artery disease.

    Directory of Open Access Journals (Sweden)

    Jessica J Connelly

    2006-08-01

    Full Text Available The transcription factor GATA2 plays an essential role in the establishment and maintenance of adult hematopoiesis. It is expressed in hematopoietic stem cells, as well as the cells that make up the aortic vasculature, namely aortic endothelial cells and smooth muscle cells. We have shown that GATA2 expression is predictive of location within the thoracic aorta; location is suggested to be a surrogate for disease susceptibility. The GATA2 gene maps beneath the Chromosome 3q linkage peak from our family-based sample set (GENECARD study of early-onset coronary artery disease. Given these observations, we investigated the relationship of several known and novel polymorphisms within GATA2 to coronary artery disease. We identified five single nucleotide polymorphisms that were significantly associated with early-onset coronary artery disease in GENECARD. These results were validated by identifying significant association of two of these single nucleotide polymorphisms in an independent case-control sample set that was phenotypically similar to the GENECARD families. These observations identify GATA2 as a novel susceptibility gene for coronary artery disease and suggest that the study of this transcription factor and its downstream targets may uncover a regulatory network important for coronary artery disease inheritance.

  14. 2014 CODEPEH recommendations: Early detection of late onset deafness, audiological diagnosis, hearing aid fitting and early intervention.

    Science.gov (United States)

    Núñez-Batalla, Faustino; Jáudenes-Casaubón, Carmen; Sequí-Canet, Jose Miguel; Vivanco-Allende, Ana; Zubicaray-Ugarteche, Jose

    2016-01-01

    The latest scientific literature considers early diagnosis of deafness as the key element to define the educational and inclusive prognosis of the deaf child, because it allows taking advantage of the critical period of development (0-4 years). Highly significant differences exist between deaf people who have been stimulated early and those who have received late or improper intervention. Early identification of late-onset disorders requires special attention and knowledge on the part of every childcare professional. Programs and additional actions beyond neonatal screening should be designed and planed to ensure that every child with a significant hearing loss is detected early. For this purpose, the CODEPEH would like to highlight the need for continuous monitoring of children's auditory health. Consequently, CODEPEH has drafted the recommendations included in the present document. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Patología Cérvico-Facial. All rights reserved.

  15. Pathogenesis of Preeclampsia: The Genetic Component

    Directory of Open Access Journals (Sweden)

    Francisco J. Valenzuela

    2012-01-01

    Full Text Available Preeclampsia (PE is one of the main causes of maternal and fetal morbidity and mortality in the world, causing nearly 40% of births delivered before 35 weeks of gestation. PE begins with inadequate trophoblast invasion early in pregnancy, which produces an increase in oxidative stress contributing to the development of systemic endothelial dysfunction in the later phases of the disease, leading to the characteristic clinical manifestation of PE. Numerous methods have been used to predict the onset of PE with different degrees of efficiency. These methods have used fetal/placental and maternal markers in different stages of pregnancy. From an epidemiological point of view, many studies have shown that PE is a disease with a strong familiar predisposition, which also varies according to geographical, socioeconomic, and racial features, and this information can be used in the prediction process. Large amounts of research have shown a genetic association with a multifactorial polygenic inheritance in the development of this disease. Many biological candidate genes and polymorphisms have been examined in their relation with PE. We will discuss the most important of them, grouped by the different pathogenic mechanisms involved in PE.

  16. Cerebrospinal Fluid Aβ43 Is Reduced in Early-Onset Compared to Late-Onset Alzheimer’s Disease, But Has Similar Diagnostic Accuracy to Aβ42

    Directory of Open Access Journals (Sweden)

    Camilla Lauridsen

    2017-06-01

    Full Text Available Background: Amyloid beta 1–43 (Aβ43 may be a useful additional biomarker for diagnosing Alzheimer’s disease (AD. We have investigated cerebrospinal fluid (CSF levels of Aβ43 in patients with early-onset AD in contrast to levels in late-onset AD. For comparison, in addition to the ‘core’ biomarkers, several other analytes were also determined [YKL-40, neurofilament light (NF-L, glial fibrillary acidic protein (GFAP, and progranulin].Material and Methods: Cerebrospinal fluid samples were obtained from patients with early-onset AD (age ≤ 62, n = 66, late-onset AD (age ≥ 68, n = 25, and groups of cognitively intact individuals (age ≤ 62, n = 41, age ≥ 68, n = 39. Core CSF AD biomarkers [amyloid beta 1–42 (Aβ42, total tau, phosphorylated tau] were analyzed, as well as levels of Aβ43 and other analytes, using commercially available enzyme-linked immunosorbent assays.Results: Cerebrospinal fluid Aβ43 was significantly reduced in early-onset AD compared to late-onset AD (14.8 ± 7.3 vs. 21.8 ± 9.4 pg/ml, respectively, whereas the levels of Aβ42 in the two AD groups were not significantly different (474.9 ± 142.0 vs. 539.6 ± 159.9 pg/ml, respectively. Aβ43 and all core biomarkers were significantly altered in patients with AD compared to corresponding controls. NF-L was significantly increased in early-onset AD compared to younger controls, an effect not found between the older groups. Relationships between the Aβ peptides and tau proteins, YKL-40, NF-L, GFAP and progranulin were also investigated without finding marked associations. However, age-associated increases in levels of tau proteins, YKL-40, NF-L and GFAP were found with respect to age in healthy controls. Results for these other analytes were similar to previously published data. Aβ43 did not improve diagnostic accuracy in either AD group compared to Aβ42. Discussion: Cerebrospinal fluid Aβ43, but not Aβ42 levels, varied significantly with age in patients with

  17. Psychological differences between early- and late-onset psoriasis: a study of personality traits, anxiety and depression in psoriasis.

    Science.gov (United States)

    Remröd, C; Sjöström, K; Svensson, A

    2013-08-01

    Onset of psoriasis may occur at any age. Early negative experiences often influence personality development, and may lead to physical disease, anxiety and depression in adulthood. Knowledge about onset of psoriasis and psychopathology is limited. To examine whether patients with early-onset psoriasis differ psychologically from patients with late-onset psoriasis, regarding personality traits, anxiety and depression. A descriptive cross-sectional study was conducted among 101 consecutively recruited outpatients with psoriasis. A psychosocial interview was performed followed by self-assessment of validated questionnaires: Swedish Universities Scales of Personality (SSP), Spielberger State-Trait Anxiety Inventory and Beck Depression Inventory. Psoriasis severity was assessed by the Psoriasis Area and Severity Index. Patients with early-onset psoriasis (age personality traits: SSP-embitterment, -trait irritability, -mistrust and -verbal trait aggression. Our results indicate that early detection of psychological vulnerability when treating children and adolescents with psoriasis seems to be of great importance. Traits of psychological vulnerability and pessimistic personality traits were found to be significantly associated with the early onset of psoriasis, but not with disease duration in this study. These traits may be seen as a consequence of psoriasis, and/or as individual traits modulating and impairing clinical course and efforts to cope with psoriasis. © 2013 The Authors BJD © 2013 British Association of Dermatologists.

  18. STAT4 polymorphism is associated with early-onset type 1 diabetes, but not with late-onset type 1 diabetes.

    Science.gov (United States)

    Lee, Hye-Soon; Park, Hyewon; Yang, Seiwon; Kim, Dukhee; Park, Yongsoo

    2008-12-01

    In an effort to discover non-HLA genes affecting susceptibility to type 1 diabetes (T1D), we have investigated the association of polymorphisms in STAT4, an important signaling molecule of IL-12, gammaIFN, and IL-23, in a sample of 389 T1D patients and 152 nondiabetic controls in Korea. Four SNPs on chromosome 2q, which were recently found to be associated with rheumatoid arthritis, were examined for association and linkage disequilibrium. We found that neither alleles or genotypes among all four SNPs nor reconstructed haplotypes of the three SNPs within the same LD block (rs7574865, rs8179673, and rs10181656) were associated with susceptibility to T1D. When we stratified T1D patients into early-onset and late-onset subgroups on the basis of fewer or more than 7.8 years of age at diagnosis, however, the minor alleles of three SNPs (rs7574865, rs8179673, and rs10181656) showed a significant association with susceptibility to T1D in the early-onset subgroup (i.e., rs7574865, OR = 1.44 [1.03-2.01], P rs7574865, rs8179673, and rs10181656) showed very comparable degrees of risk for T1D. The age at diagnosis is lowest in the patients carrying the homozygotes of a minor allele, middle in the heterozygotes, and highest in the homozygotes of a major allele, suggesting the dosage effects of risk alleles on the age of onset of disease. Recognizing that only the early-onset cases might represent the true autoimmune T1D in Asian populations, we see that STAT4 alleles and haplotype might influence cytokine signaling and, therefore, development of T1D.

  19. Voxel-based structural magnetic resonance imaging (MRI study of patients with early onset schizophrenia

    Directory of Open Access Journals (Sweden)

    Suzuki Katsuaki

    2008-12-01

    Full Text Available Abstract Background Investigation into the whole brain morphology of early onset schizophrenia (EOS to date has been sparse. We studied the regional brain volumes in EOS patients, and the correlations between regional volume measures and symptom severity. Methods A total of 18 EOS patients (onset under 16 years and 18 controls matched for age, gender, parental socioeconomic status, and height were examined. Voxel-based morphometric analysis using the Brain Analysis Morphological Mapping (BAMM software package was employed to explore alterations of the regional grey (GM and white matter (WM volumes in EOS patients. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS. Results EOS patients had significantly reduced GM volume in the left parahippocampal, inferior frontal, and superior temporal gyri, compared with the controls. They also had less WM volume in the left posterior limb of the internal capsule and the left inferior longitudinal fasciculus. The positive symptom score of PANSS (higher values corresponding to more severe symptoms was negatively related to GM volume in the bilateral posterior cingulate gyrus. The negative symptom score was positively correlated with GM volume in the right thalamus. As for the association with WM volume, the positive symptom score of PANSS was positively related to cerebellar WM (vermis region, and negatively correlated with WM in the brain stem (pons and in the bilateral cerebellum (hemisphere region. Conclusion Our findings of regional volume alterations of GM and WM in EOS patients coincide with those of previous studies of adult onset schizophrenia patients. However, in brain regions that had no overall structural differences between EOS patients and controls (that is, the bilateral posterior cingulate gyrus, the right thalamus, the cerebellum, and the pons, within-subject analysis of EOS patients alone revealed that there were significant associations of the volume in these areas

  20. Screening and Treatment for Early-Onset Gestational Diabetes Mellitus: a Systematic Review and Meta-analysis.

    Science.gov (United States)

    Immanuel, Jincy; Simmons, David

    2017-10-02

    We conducted a systematic review to evaluate the current evidence for screening and treatment for early-onset gestational diabetes mellitus (GDM) RECENT FINDINGS: Many of the women with early GDM in the first trimester do not have evidence of hyperglycemia at 24-28 weeks' gestation. A high proportion (15-70%) of women with GDM can be detected early in pregnancy depending on the setting, criteria used and screening strategy. However, there remains no good evidence for any of the diagnostic criteria for early-onset GDM. In a meta-analysis of 13 cohort studies, perinatal mortality (relative risk (RR) 3.58 [1.91, 6.71]), neonatal hypoglycemia (RR 1.61 [1.02, 2.55]), and insulin use (RR 1.71 [1.45, 2.03]) were greater among early-onset GDM women compared to late-onset GDM women, despite treatment. Considering the high likelihood of benefit from treatment, there is an urgent need for randomized controlled trials that investigate any benefits and possible harms of treatment of early-onset GDM.

  1. Doppler flowmetry in preeclampsia.

    Science.gov (United States)

    Zahumensky, J

    2009-01-01

    The purpose of this study was to summarize the new published data on the Doppler flowmetry in preeclampsia. We summarize the new published data on the Doppler flowmetry in uteroplacental, fetoplacental and fetal circulation in preeclampsia. The present review summarized the results of clinical research on the Doppler flowmetry in the screening of risk of preclampsia, in the diagnosis of preclampsia and in the fetal risk in preclampsia (Ref. 19). Full Text (Free, PDF) www.bmj.sk.

  2. Profile of cognitive deficits and associations with depressive symptoms and intelligence in chronic early-onset schizophrenia patients

    DEFF Research Database (Denmark)

    Jepsen, Jens Richardt Møllegaard; Fagerlund, Birgitte; Pagsberg, Anne Katrine

    2013-01-01

    , early-onset schizophrenia patients (mean age = 20.7 years) (N = 18) and healthy controls (N = 38). Schizophrenia diagnoses were established at the time of the patients' first clinical presentation during childhood or adolescence and were confirmed five years later. In the chronic phase of early...

  3. Biomarker development for presymptomatic molecular diagnosis of preeclampsia: feasible, useful or even unnecessary?

    Science.gov (United States)

    Hahn, Sinuhe; Lapaire, Olav; Than, Nandor Gabor

    2015-05-01

    The past decade saw the advent of a number of promising biomarkers to detect pregnancies at risk for preeclampsia (PE), the foremost being those associated with an imbalance of angiogenic factors. In late pregnancy, these are useful for the detection of imminent cases of PE, while earlier they were more predictive for early- than late-onset PE. This suggests that there may be fundamental differences between the underlying pathology of these two PE forms. Therefore, it is possible that such a biological premise may limit the development of biomarkers that will permit the efficacious detection of both early- and late-onset PE via an analysis of first-trimester maternal blood samples. Consequently, a significant increase in our understanding of the underlying pathology of PE, using a variety of approaches ranging from systems biology to animal models, will be necessary in order to overcome this obstacle.

  4. CDKL5 mutations cause infantile spasms, early onset seizures, and severe mental retardation in female patients

    Science.gov (United States)

    Archer, H L; Evans, J; Edwards, S; Colley, J; Newbury‐Ecob, R; O'Callaghan, F; Huyton, M; O'Regan, M; Tolmie, J; Sampson, J; Clarke, A; Osborne, J

    2006-01-01

    Objective To determine the frequency of mutations in CDKL5 in both male and female patients with infantile spasms or early onset epilepsy of unknown cause, and to consider whether the breadth of the reported phenotype would be extended by studying a different patient group. Methods Two groups of patients were investigated for CDKL5 mutations. Group 1 comprised 73 patients (57 female, 16 male) referred to Cardiff for CDKL5 analysis, of whom 49 (42 female, 7 male) had epileptic seizure onset in the first six months of life. Group 2 comprised 26 patients (11 female, 15 male) with infantile spasms previously recruited to a clinical trial, the UK Infantile Spasms Study. Where a likely pathogenic mutation was identified, further clinical data were reviewed. Results Seven likely pathogenic mutations were found among female patients from group 1 with epileptic seizure onset in the first six months of life, accounting for seven of the 42 in this group (17%). No mutations other than the already published mutation were found in female patients from group 2, or in any male patient from either study group. All patients with mutations had early signs of developmental delay and most had made little developmental progress. Further clinical information was available for six patients: autistic features and tactile hypersensitivity were common but only one had suggestive Rett‐like features. All had a severe epileptic seizure disorder, all but one of whom had myoclonic jerks. The EEG showed focal or generalised changes and in those with infantile spasms, hypsarrhythmia. Slow frequencies were seen frequently with a frontal or fronto‐temporal predominance and high amplitudes. Conclusions The spectrum of the epileptic seizure disorder, and associated EEG changes, in those with CDKL5 mutations is broader than previously reported. CDKL5 mutations are a significant cause of infantile spasms and early epileptic seizures in female patients, and of a later intractable seizure disorder

  5. Alcohol use in motion pictures and its relation with early-onset teen drinking.

    Science.gov (United States)

    Sargent, James D; Wills, Thomas A; Stoolmiller, Mike; Gibson, Jennifer; Gibbons, Frederick X

    2006-01-01

    Little is known about the impact of viewing depictions of alcohol in entertainment media on adolescent drinking behavior. Our aims were to assess drinking in a sample of popular contemporary movies and to examine the association of movie alcohol exposure with early-onset drinking in an adolescent sample. We conducted a school-based cross-sectional survey (N=4655) with longitudinal follow-up of never-drinkers (N=2406) involving adolescents ages 10-14 years and recruited from 15 New Hampshire and Vermont schools. Screen depictions of alcohol use were timed for each of 601 popular contemporary movies. Each adolescent was asked if he/she had seen a unique list of 50 movie titles, randomly selected from the larger pool. Movie alcohol use was summed for movies the adolescent had seen, adjusted to reflect exposure to the larger pool and modeled as a continuous variable. Ninety-two percent of the movies in the sample depicted drinking; median screen time for movie alcohol use was 2.5 minutes (interquartile range [IQR]: 0.9-5.0 minutes). Median exposure to movie alcohol use from the 601 movies was 8.6 hours (IQR: 4.6-13.5 hours). Overall 23.1% of the cross-sectional sample had tried alcohol, and 14.8% of initial nondrinkers had tried alcohol at the follow-up assessment. We found statistical evidence to support a curvilinear association between higher exposure to movie alcohol use and increased risk of prevalent and incident alcohol use, with a statistically significant linear and quadratic effect, and suggesting a higher dose-effect relationship at lower movie alcohol exposure levels compared to higher levels. The linear and the quadratic associations remained strong and significant in cross-sectional and prospective models after controlling for sociodemographics (grade in school, school, gender, parent education), personality characteristics of the adolescent (sensation seeking, rebelliousness, self-esteem), school performance, parenting style, and smoking experimentation

  6. Early-Onset Invasive Candidiasis in Extremely Low Birth Weight Infants: Perinatal Acquisition Predicts Poor Outcome.

    Science.gov (United States)

    Barton, Michelle; Shen, Alex; O'Brien, Karel; Robinson, Joan L; Davies, H Dele; Simpson, Kim; Asztalos, Elizabeth; Langley, Joanne; Le Saux, Nicole; Sauve, Reginald; Synnes, Anne; Tan, Ben; de Repentigny, Louis; Rubin, Earl; Hui, Chuck; Kovacs, Lajos; Yau, Yvonne C W; Richardson, Susan E

    2017-04-01

    Neonatal invasive candidiasis (IC) presenting in the first week of life is less common and less well described than later-onset IC. Risk factors, clinical features, and disease outcomes have not been studied in early-onset disease (EOD, ≤7 days) or compared to late-onset disease (LOD, >7 days). All extremely low birth weight (ELBW, candidiasis enrolled from 2001 to 2003 were included in this study. Factors associated with occurrence and outcome of EOD in ELBW infants were determined. Forty-five ELBW infants and their 84 matched controls were included. Fourteen (31%) ELBW infants had EOD. Birth weight <750 g, gestation <25 weeks, chorioamnionitis, and vaginal delivery were all strongly associated with EOD. Infection with Candida albicans, disseminated disease, pneumonia, and cardiovascular disease were significantly more common in EOD than in LOD. The EOD case fatality rate (71%) was higher than in LOD (32%) or controls (15%) (P = .0001). The rate of neurodevelopmental impairment and mortality combined was similar in EOD (86%) and LOD (72%), but higher than in controls (32%; P = .007). ELBW infants with EOD have a very poor prognosis compared to those with LOD. The role of perinatal transmission in EOD is supported by its association with chorioamnionitis, vaginal delivery, and pneumonia. Dissemination and cardiovascular involvement are common, and affected infants often die. Empiric treatment should be considered for ELBW infants delivered vaginally who have pneumonia and whose mothers have chorioamnionitis or an intrauterine foreign body. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  7. Exploring reasons for late identification of children with early-onset hearing loss.

    Science.gov (United States)

    Fitzpatrick, Elizabeth M; Dos Santos, Johnny Cesconetto; Grandpierre, Viviane; Whittingham, JoAnne

    2017-09-01

    Several studies have shown that early identification of childhood hearing loss leads to better language outcomes. However, delays in the confirmation of hearing loss persist even in the presence of well-established universal newborn hearing screening programs (UNHS). The objective of this population-based study was to document the proportion of children who experienced delayed confirmation of congenital and early onset hearing loss in a UNHS program in one region of Canada. The study also sought to determine the reasons for delayed confirmation of hearing loss in children. Population level data related to age of first assessment, age of identification and clinical characteristics were collected prospectively for all children identified through the UNHS program. We documented the number of children who experienced delay (defined as more than 3 months) from initial audiologic assessment to confirmation of hearing loss. A detailed chart review was subsequently performed to examine the reasons for delay to confirmation. Of 418 children identified from 2003 to 2013, 182 (43.5%) presented with congenital or early onset hearing loss, of whom 30 (16.5%) experienced more than 3 months delay from initial audiologic assessment to confirmation of their hearing disorder. The median age of first assessment and confirmation of hearing loss for these 30 children was 3.7 months (IQR: 2.0, 7.6) and 13.8 months (IQR: 9.7, 26.1) respectively. Close examination of the factors related to delay to confirmation revealed that for the overwhelming majority of children, a constellation of factors contributed to late diagnosis. Several children (n = 22; 73.3%) presented with developmental/medical issues, 15 of whom also had middle ear dysfunction at assessment, and 9 of whom had documented family follow-up concerns. For the remaining eight children, additional reasons included ongoing middle ear dysfunction for five children, complicated by family follow-up concerns (n = 3) and mild

  8. Maternal Preeclampsia and Androgens in the Offspring around Puberty: A Follow-Up Study.

    Directory of Open Access Journals (Sweden)

    Ingvild V Alsnes

    Full Text Available Children born after preeclampsia may have a dominant androgen profile in puberty compared with other children. Circulating androgen concentrations at 11-12 years of age were compared between offspring born after preeclampsia, and children whose mothers did not have preeclampsia.A total of 611 mother-offspring pairs were followed up 11 (daughters or 12 (sons years after birth: 218 pairs in the preeclampsia group, and 383 pairs without preeclampsia. Circulating total testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS, and insulin-like growth factor I (IGF-I were measured in the children. In boys, testicular volume was also measured.Among girls born after preeclampsia, DHEAS concentrations were higher than in unexposed girls (p<0.001, however, girls born after preeclampsia with severe features had the lowest DHEAS levels. In contrast, testosterone concentrations were highest in girls born after preeclampsia with severe features, both compared to other girls in the preeclampsia group, and compared to unexposed girls (p<0.001. For boys, testosterone concentrations were higher in the preeclampsia group compared with unexposed boys (p<0.001, and boys born after preeclampsia with severe features had the lowest concentrations of DHEAS. Compared with unexposed boys, testicular volume (p = 0.015 and IGF-I (p = 0.004 were higher for boys in the preeclampsia group, except for boys in the clinically severe preeclampsia group.In utero exposure to preeclampsia is associated with androgen hormonal patterns in early puberty that depend on clinical severity of preeclampsia and sex of the offspring. The hormonal differences may reflect different timing of pubertal development, and may have consequences for future health of the offspring.

  9. Genetic Risk Score for Essential Hypertension and Risk of Preeclampsia.

    Science.gov (United States)

    Smith, Caitlin J; Saftlas, Audrey F; Spracklen, Cassandra N; Triche, Elizabeth W; Bjonnes, Andrew; Keating, Brendan; Saxena, Richa; Breheny, Patrick J; Dewan, Andrew T; Robinson, Jennifer G; Hoh, Josephine; Ryckman, Kelli K

    2016-01-01

    Preeclampsia is a hypertensive complication of pregnancy characterized by novel onset of hypertension after 20 weeks gestation, accompanied by proteinuria. Epidemiological evidence suggests that genetic susceptibility exists for preeclampsia; however, whether preeclampsia is the result of underlying genetic risk for essential hypertension has yet to be investigated. Based on the hypertensive state that is characteristic of preeclampsia, we aimed to determine if established genetic risk scores (GRSs) for hypertension and blood pressure are associated with preeclampsia. Subjects consisted of 162 preeclamptic cases and 108 normotensive pregnant controls, all of Iowa residence. Subjects' DNA was extracted from buccal swab samples and genotyped on the Affymetrix Genome-wide Human SNP Array 6.0 (Affymetrix, Santa Clara, CA). Missing genotypes were imputed using MaCH and Minimac software. GRSs were calculated for hypertension, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) using established genetic risk loci for each outcome. Regression analyses were performed to determine the association between GRS and risk of preeclampsia. These analyses were replicated in an independent US population of 516 cases and 1,097 controls of European ancestry. GRSs for hypertension, SBP, DBP, and MAP were not significantly associated with risk for preeclampsia (P > 0.189). The results of the replication analysis also yielded nonsignificant associations. GRSs for hypertension and blood pressure are not associated with preeclampsia, suggesting that an underlying predisposition to essential hypertension is not on the causal pathway of preeclampsia. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. The Utility of the Addenbrooke's Cognitive Examination Version Three in Early-Onset Dementia.

    Science.gov (United States)

    Elamin, Marwa; Holloway, Guy; Bak, Thomas H; Pal, Suvankar

    2016-01-01

    Early-onset dementia (EOD) is defined as functionally relevant cognitive decline with age of onset at less than 65 years. The aim of this study was to investigate the utility of the recently validated third version of the Addenbrooke's Cognitive Examination (ACE-III) in predicting dementia diagnoses in EOD. ACE-III scores of EOD patients were compared to those of healthy controls (HC) and individuals with subjective memory impairment (SMI). The study included 71 EOD patients (Alzheimer's disease, n = 31; primary progressive aphasia, n = 11; behavioural-variant frontotemporal dementia, n = 18, and posterior cortical atrophy, n = 11); there were 28 HC and 15 individuals with SMI. At a cut-off score of 88/100, the ACE-III displayed high sensitivity and specificity in distinguishing EOD from HC (91.5 and 96.4%) and SMI (91.5 and 86.7%). The ACE-III is a reliable cognitive screening tool in EOD. © 2015 S. Karger AG, Basel.

  11. Rapidly-growing mycobacterial infection: a recognized cause of early-onset prosthetic joint infection.

    Science.gov (United States)

    Jitmuang, Anupop; Yuenyongviwat, Varah; Charoencholvanich, Keerati; Chayakulkeeree, Methee

    2017-12-28

    Prosthetic joint infection (PJI) is a major complication of total hip and total knee arthroplasty (THA, TKA). Although mycobacteria are rarely the causative pathogens, it is important to recognize and treat them differently from non-mycobacterial infections. This study aimed to compare the clinical characteristics, associated factors and long-term outcomes of mycobacterial and non-mycobacterial PJI. We conducted a retrospective case-control study of patients aged ≥18 years who were diagnosed with PJI of the hip or knee at Siriraj Hospital from January 2000 to December 2012. Patient characteristics, clinical data, treatments and outcomes were evaluated. A total of 178 patients were included, among whom 162 had non-mycobacterial PJI and 16 had mycobacterial PJI. Rapidly growing mycobacteria (RGM) (11) and M. tuberculosis (MTB) (5) were the causative pathogens of mycobacterial PJI. PJI duration and time until onset were significantly different between mycobacterial and non-mycobacterial PJI. Infection within 90 days of arthroplasty was significantly associated with RGM infection (OR 21.86; 95% CI 4.25-112.30; p infection. RGM were the major pathogens of early onset PJI after THA and TKA. Both a high clinical index of suspicion and mycobacterial cultures are recommended when medically managing PJI with negative cultures or non-response to antibiotics. Removal of infected implants was associated with favorable outcomes.

  12. Maintaining intestinal health: the genetics and immunology of very early onset inflammatory bowel disease.

    Science.gov (United States)

    Kelsen, Judith R; Baldassano, Robert N; Artis, David; Sonnenberg, Gregory F

    2015-09-01

    Inflammatory bowel disease (IBD) is a multifactoral disease caused by dysregulated immune responses to commensal or pathogenic microbes in the intestine, resulting in chronic intestinal inflammation. An emerging population of patients with IBD occurring before the age of 5 represent a unique form of disease, termed Very Early Onset (VEO)-IBD, which is phenotypically- and genetically-distinct from older-onset IBD. VEO-IBD is associated with increased disease severity, aggressive progression and poor responsiveness to most conventional therapies. Further investigation into the causes and pathogenesis of VEO-IBD will help improve treatment strategies, and may lead to a better understanding of the mechanisms that are essential to maintain intestinal health or provoke the development of targeted therapeutic strategies to limit intestinal disease. Here we discuss the phenotypic nature of VEO-IBD, the recent identification of novel gene variants associated with disease, and functional immunologic studies interrogating the contribution of specific genetic variants to the development of chronic intestinal inflammation.

  13. The role of monogenic disease in children with very early onset inflammatory bowel disease.

    Science.gov (United States)

    Kelsen, Judith R; Baldassano, Robert N

    2017-10-01

    Inflammatory bowel disease (IBD) is a multifactorial disease caused by dysregulated immune responses to commensal or pathogenic intestinal microbes, resulting in chronic intestinal inflammation. Patients diagnosed with IBD occurring before the age of 5 are a unique population, known as very early onset (VEO)-IBD and can be phenotypically and genetically distinct from older-onset IBD. We aim to review the clinical presentation of children with VEO-IBD and recent discoveries that point to genomic drivers of disease that may impact our therapeutic decisions. VEO-IBD is increasing in incidence and is associated with more severe disease, aggressive progression and poor response to most conventional therapies. This article will review the advances in sequencing technology that have led to identification of novel gene variants associated with disease and potentially new targeted therapeutic options. Children with VEO-IBD may present with a different phenotype and more severe disease than older children and adults. Identification of the causal gene or pathways, these children may allow for true precision medicine with targeted therapy and improved disease course.

  14. A randomized controlled trial of two primary school intervention strategies to prevent early onset tobacco smoking.

    Science.gov (United States)

    Storr, Carla L; Ialongo, Nicholas S; Kellam, Sheppard G; Anthony, James C

    2002-03-01

    In this article, we examine the impact of two universal, grade 1 preventive interventions on the onset of tobacco smoking as assessed in early adolescence. The classroom-centered (CC) intervention was designed to reduce the risk for tobacco smoking by enhancing teachers' behavior management skills in first grade and, thereby, reducing child attention problems and aggressive and shy behavior-known risk behaviors for later substance use. The family-school partnership (FSP) intervention targeted these early risk behaviors via improvements in parent-teacher communication and parents' child behavior management strategies. A cohort of 678 urban, predominately African-American, public school students were randomly assigned to one of three Grade 1 classrooms at entrance to primary school (age 6). One classroom featured the CC intervention, a second the FSP intervention, and the third served as a control classroom. Six years later, 81% of the students completed audio computer-assisted self-interviews. Relative to controls, a modest attenuation in the risk of smoking initiation was found for students who had been assigned to either the CC or FSP intervention classrooms (26% versus 33%) (adjusted relative risk for CC/control contrast=0.57, 95% confidence interval (CI), 0.34-0.96; adjusted relative risk for FSP/control contrast=0.69, 95% CI, 0.50-0.97). Results lend support to targeting the early antecedent risk behaviors for tobacco smoking.

  15. Early-onset behavioral and neurochemical deficits in the genetic mouse model of phenylketonuria.

    Science.gov (United States)

    Fiori, Elena; Oddi, Diego; Ventura, Rossella; Colamartino, Marco; Valzania, Alessandro; D'Amato, Francesca Romana; Bruinenberg, Vibeke; van der Zee, Eddy; Puglisi-Allegra, Stefano; Pascucci, Tiziana

    2017-01-01

    Phenylketonuria (PKU) is one of the most common human inborn errors of metabolism, caused by phenylalanine hydroxylase deficiency, leading to high phenylalanine and low tyrosine levels in blood and brain causing profound cognitive disability, if untreated. Since 1960, population is screened for hyperphenylalaninemia shortly after birth and submitted to early treatment in order to prevent the major manifestations of the disease. However, the dietetic regimen (phenylalanine free diet) is difficult to maintain, and despite the recommendation to a strict and lifelong compliance, up to 60% of adolescents partially or totally abandons the treatment. The development and the study of new treatments continue to be sought, taking advantage of preclinical models, the most used of which is the PAHenu2 (BTBR ENU2), the genetic murine model of PKU. To date, adult behavioral and neurochemical alterations have been mainly investigated in ENU2 mice, whereas there are no clear indications about the onset of these deficiencies. Here we investigated and report, for the first time, a comprehensive behavioral and neurochemical assay of the developing ENU2 mice. Overall, our findings demonstrate that ENU2 mice are significantly smaller than WT until pnd 24, present a significant delay in the acquisition of tested developmental reflexes, impaired communicative, motor and social skills, and have early reduced biogenic amine levels in several brain areas. Our results extend the understanding of behavioral and cerebral abnormalities in PKU mice, providing instruments to an early preclinical evaluation of the effects of new treatments.

  16. Phenotype variability and early onset ataxia symptoms in spinocerebellar ataxia type 7: comparison and correlation with other spinocerebellar ataxias

    Directory of Open Access Journals (Sweden)

    Marcus Vinicius Cristino de Albuquerque

    2015-01-01

    Full Text Available The spinocerebellar ataxias (SCA are a group of neurodegenerative disorders characterized by heterogeneous clinical presentation. Spinocerebellar ataxia type 7 (SCA7 is caused by an abnormal CAG repeat expansion and includes cerebellar signs associated with visual loss and ophthalmoplegia. Marked anticipation and dynamic mutation is observed in SCA7. Moreover, phenotype variability and very early onset of symptoms may occur. In this article, a large series of Brazilian patients with different SCA subtypes was evaluated, and we compared the age of onset of SCA7 with other SCA. From the 26 patients with SCA7, 4 manifested their symptoms before 10-year-old. Also, occasionally the parents may have the onset of symptoms after their children. In conclusion, our study highlights the genetic anticipation phenomenon that occurs in SCA7 families. Patients with very early onset ataxia in the context of a remarkable family history, must be considered and tested for SCA7.

  17. Novel CDKL5 Mutations in Czech Patients with Phenotypes of Atypical Rett Syndrome and Early-Onset Epileptic Encephalopathy.

    Science.gov (United States)

    Záhoráková, D; Langová, M; Brožová, K; Laštůvková, J; Kalina, Z; Rennerová, L; Martásek, P

    2016-01-01

    The X-linked CDKL5 gene, which encodes cyclin-dependent kinase-like 5 protein, has been implicated in early-onset encephalopathy and atypical Rett syndrome with early-onset seizures. The CDKL5 protein is a kinase required for neuronal development and morphogenesis, but its precise functions are still largely unexplored. Individuals with CDKL5 mutations present with severe global developmental delay, intractable epilepsy, and Rett-like features. A clear genotype-phenotype correlation has not been established due to an insufficient number of reported cases. The aim of this study was to analyse the CDKL5 gene in Czech patients with early-onset seizures and Rett-like features. We performed mutation screening in a cohort of 83 individuals using high-resolution melting analysis, DNA sequencing and multiplex ligation- dependent probe amplification. Molecular analyses revealed heterozygous pathogenic mutations in three girls with severe intellectual disability and intractable epilepsy starting at the age of two months. All three identified mutations, c.637G>A, c.902_977+29del105, and c.1757_1758delCT, are novel, thus significantly extending the growing spectrum of known pathogenic CDKL5 sequence variants. Our results support the importance of genetic testing of the CDKL5 gene in patients with early-onset epileptic encephalopathy and Rett-like features with early-onset seizures. This is the first study referring to molecular defects of CDKL5 in Czech cases.

  18. Completed suicide in an autopsy-confirmed case of early onset Alzheimer's disease.

    Science.gov (United States)

    Hartzell, Jennifer Wiener; Geary, Richard; Gyure, Kymberly; Chivukula, Venkata Ravi; Haut, Marc W

    2018-04-01

    We report a case of a 57-year-old male with clinically diagnosed and autopsy-confirmed early onset Alzheimer's disease who completed suicide by gunshot wound to the chest. This case has several unique aspects that have not been discussed in previous case reports of completed suicide in Alzheimer's disease. In particular, our patient's death was highly planned with successful compensation for his cognitive deficits. After all firearms had been removed from the home as a safety precaution, he obtained a new weapon, hid it and left himself cues to find and use it. The case is discussed in the context of literature differentiating the neural circuitry propagating impulsive versus planned suicidal acts.

  19. Ultrasound control of magnet growing rod distraction in early onset scoliosis.

    Science.gov (United States)

    Pérez Cervera, T; Lirola Criado, J F; Farrington Rueda, D M

    2016-01-01

    The growing rod technique is currently one of the most common procedures used in the management of early onset scoliosis. However, in order to preserve spine growth and control the deformity it requires frequent surgeries to distract the rods. Magnetically driven growing rods have recently been introduced with same treatment goal, but without the inconvenience of repeated surgical distractions. One of the limitations of this technical advance is an increase in radiation exposure due to the increase in distraction frequency compared to conventional growing rods. An improvement of the original technique is presented, proposing a solution to the inconvenience of multiple radiation exposure using ultrasound technology to control the distraction process of magnetically driven growing rods. Copyright © 2014 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Design of a Dynamic Spinal Implant for the treatment of Early Onset Scoliosis

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    Gonzalez Alvarez, A.; Shepherd, D.; Dearn, K.

    2016-07-01

    GSDyn (Growing Spine Dynamic) is a novel implant that has been designed and manufactured to mechanically correct three dimensional spinal deformities in children with Early Onset Scoliosis (EOS). The innovative element of the implant is the lengthening mechanism that allows the elongation surgeries to be easier, faster and less invasive procedures than with other mechanical implants on the market, as they can be performed under local anaesthetics and with a surgical incision of less than one centimetre. It also includes a dynamic system to prevent implant breakage and anchor loosening, two of the most common complications occurring in this treatment. The development of the implant has been guided by spinal surgeons. Finite Element Analysis has been performed to evaluate the behaviour of the device under different loading conditions and two working prototypes have been successfully manufactured. (Author)

  1. Perceptions of stigma among people affected by early- and late-onset Alzheimer's disease.

    Science.gov (United States)

    Ashworth, Rosalie

    2017-07-01

    The aim of this research was to explore perceptions of stigma among people with early- and late-onset Alzheimer's disease and those who support them, using questionnaires ( n = 44) and semi-structured interviews ( n = 14). Perceived stigma reporting was low in the questionnaires, whereas interviews revealed higher levels of perceived stigma in the form of unpredictable reactions to diagnosis, feeling stupid and ignorance of the condition among the public. Perceived stigma was managed in similar ways across age groups, focusing on 'being the lucky ones'. Results support the need to further tackle stigma and challenge expectations, particularly given the drive to diagnose people and thereby expose them to stigma.

  2. Investigating autism spectrum disorder and autistic traits in early onset eating disorder.

    Science.gov (United States)

    Pooni, Jyoti; Ninteman, Aafke; Bryant-Waugh, Rachel; Nicholls, Dasha; Mandy, William

    2012-05-01

    To investigate whether young people (8-16 years) with an eating disorder have a higher prevalence of autism spectrum disorder (ASDs) and elevated autistic traits compared to typically developing (TD) peers. Twenty-two participants with early onset eating disorder (EOED) were assessed using standardized ASD measures and compared to IQ matched TD (n = 24) and ASD (n = 20) controls. An ASD diagnosis was no more common in EOED than in TD controls. However, repetitive and stereotyped behavior was more often observed in the EOED group and, compared to TD controls, there was a trend (p = .07) toward greater autistic social impairment in EOED. Whilst participants with EOED did not show increased ASD prevalence, they did have elevated autistic traits of clinical significance, particularly repetitive and stereotyped behavior. Further work is required to determine whether inflexibility and social difficulties in EOED have identical phenomenology and etiology to those seen in ASD. Copyright © 2012 Wiley Periodicals, Inc.

  3. Severe agitation in severe early-onset Alzheimer’s disease resolves with ECT

    Directory of Open Access Journals (Sweden)

    Aksay SS

    2014-11-01

    Full Text Available Suna Su Aksay, Lucrezia Hausner, Lutz Frölich, Alexander Sartorius Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany Abstract: Dementia-related behavioral disturbances are mostly treated with antipsychotics; however, the observed beneficial effects are modest and the risk of serious adverse effects high. We report the case of a 57-year-old woman with severe early-onset Alzheimer’s disease and severe agitation, whom we treated with electroconvulsive therapy (ECT. A significant clinical improvement was achieved over eight ECT sessions, which were tolerated well without cognitive worsening, and lasted approximately 3 months. Our case demonstrates the safe and effective use of ECT in pharmacotherapy-resistant severe agitation in Alzheimer’s disease. The risk–benefit profile of ECT for dementia-related agitation should be further investigated in clinical trials. Keywords: dementia, electroconvulsive therapy, cognition, emotional distress, disinhibition.

  4. STRIDER (Sildenafil TheRapy in dismal prognosis early onset fetal growth restriction)

    DEFF Research Database (Denmark)

    Pels, A; Kenny, L C; Alfirevic, Z

    2017-01-01

    randomised placebo-controlled trials have been launched. Women with a singleton pregnancy between 18 and 30 weeks with severe fetal growth restriction of likely placental origin, and where the likelihood of perinatal death/severe morbidity is estimated to be significant are included. Participants......BACKGROUND: Severe, early-onset fetal growth restriction due to placental insufficiency is associated with a high risk of perinatal mortality and morbidity with long-lasting sequelae. Placental insufficiency is the result of abnormal formation and function of the placenta with inadequate...... Restriction (STRIDER) collaboration is to evaluate the effectiveness of sildenafil versus placebo in achieving healthy perinatal survival through the conduct of randomised clinical trials and systematic review including individual patient data meta-analysis. METHODS: Five national/bi-national multicentre...

  5. Clinical, genetic, and neuroimaging features of Early Onset Alzheimer Disease: the challenges of diagnosis and treatment.

    Science.gov (United States)

    Alberici, Antonella; Benussi, Alberto; Premi, Enrico; Borroni, Barbara; Padovani, Alessandro

    2014-01-01

    Early Onset Alzheimer Disease (EOAD) is a rare condition, frequently associated with genetic causes. The dissemination of genetic testing along with biomarker determinations have prompted a wider recognition of EOAD in experienced clinical settings. However, despite the great efforts in establishing the contribution of causative genes to EOAD, atypical disease presentation and clinical features still makes its diagnosis and treatment a challenge for the clinicians. This review aims to provide an extensive evaluation of literature data on EOAD, in order to improve understanding and knowledge of EOAD, underscore its significant impact on patients and their caregivers and influence public policies. This would be crucial to define the urgency of evidence-based treatment approaches.

  6. PRODROMAL PHASE IN THE DEVELOPMENT OF EARLY ONSET SCHIZOPHRENIC PSYCHOSIS - CASE REPORT

    Directory of Open Access Journals (Sweden)

    Jelena Kostić

    2012-06-01

    Full Text Available Schizophrenia and other mental disorders are often preceded by prodromal changes in behavior that can last from several days to several years, indicating the beginning of psychosis. If the disease starts at an earlier age, especially in adolescence, the prodromal phase is more non-specific and difficult to detect. There is a large number of operational instruments used for clinical assessment and quantification of prodromal symptoms and "at risk mental state", as well as the predictive potential for psychosis. This paper describes the prodromal phase in the development of early onset schizophrenic psychosis, with the emphasis on gradual, several-month psychopathological accumulation and evolution of nonspecific and subclinical, prodromal symptoms to florid schizophrenic symptoms.

  7. Relationship of early-onset baldness to prostate cancer in African-American men.

    Science.gov (United States)

    Zeigler-Johnson, Charnita; Morales, Knashawn H; Spangler, Elaine; Chang, Bao-Li; Rebbeck, Timothy R

    2013-04-01

    Early-onset baldness has been linked to prostate cancer; however, little is known about this relationship in African-Americans who are at elevated prostate cancer risk. We recruited 219 African-American controls and 318 African-American prostate cancer cases. We determined age-stratified associations of baldness with prostate cancer occurrence and severity defined by high stage (T3/T4) or high grade (Gleason 7+.) Associations of androgen metabolism genotypes (CYP3A4, CYP3A5, CYP3A43, AR-CAG, SRD5A2 A49T, and SRD5A2 V89L), family history, alcohol intake, and smoking were examined by baldness status and age group by using multivariable logistic regression models. Baldness was associated with odds of prostate cancer [OR = 1.69; 95% confidence interval (CI), 1.05-2.74]. Frontal baldness was associated with high-stage (OR = 2.61; 95% CI, 1.10-6.18) and high-grade (OR = 2.20; 95% CI, 1.05-4.61) tumors. For men diagnosed less than the age of 60 years, frontal baldness was associated with high stage (OR = 6.51; 95% CI, 2.11-20.06) and high grade (OR = 4.23; 95% CI, 1.47-12.14). We also observed a suggestion of an interaction among smoking, median age, and any baldness (P = 0.02). We observed significant associations between early-onset baldness and prostate cancer in African-American men. Interactions with age and smoking were suggested in these associations. Studies are needed to investigate the mechanisms influencing the relationship between baldness and prostate cancer in African-American men. African-American men present with unique risk factors including baldness patterns that may contribute to prostate cancer disparities.

  8. Relationship of Early Onset Baldness to Prostate Cancer in African-American Men

    Science.gov (United States)

    Zeigler-Johnson, Charnita; Morales, Knashawn H.; Spangler, Elaine; Chang, Bao-Li; Rebbeck, Timothy R.

    2013-01-01

    Background Early onset baldness has been linked to prostate cancer (CaP), however, little is known about this relationship in African Americans (AA) who are at elevated CaP risk. Methods We recruited 219 AA controls and 318 AA CaP cases. We determined age-stratified associations of baldness with CaP occurrence and severity defined by high stage (T3/T4) or high grade (Gleason 7+.) Associations of androgen metabolism genotypes (CYP3A4, CYP3A5, CYP3A43, AR-CAG, SRD5A2 A49T, and SRD5A2 V89L), family history, alcohol intake, and smoking were examined by baldness status and age group by using multivariable logistic regression models. Results Baldness was associated with odds of CaP (OR=1.69, 95% CI=1.05–2.74). Frontal baldness was associated with high stage (OR=2.61, 95% CI=1.10–6.18) and high grade (OR=2.20, 95% CI=1.05–4.61) tumors. For men diagnosed less than age 60, frontal baldness was associated with high stage (OR=6.51, 95% CI=2.11–20.06) and high grade (OR=4.23, 95% CI=1.47–12.14). We also observed a suggestion of an interaction among smoking, median age and any baldness (p=0.02). Conclusions We observed significant associations between early onset baldness and CaP in AA men. Interactions with age and smoking were suggested in these associations. Studies are needed to investigate the mechanisms influencing the relationship between baldness and CaP in AA. Impact AA men present with unique risk factors including baldness patterns that may contribute to CaP disparities. PMID:23532004

  9. Clinical dissection of early onset absence epilepsy in children and prognostic implications.

    Science.gov (United States)

    Agostinelli, Sergio; Accorsi, Patrizia; Beccaria, Francesca; Belcastro, Vincenzo; Canevini, Maria Paola; Capovilla, Giuseppe; Cappanera, Silvia; Dalla Bernardina, Bernardo; Darra, Francesca; Del Gaudio, Luigi; Elia, Maurizio; Falsaperla, Raffaele; Giordano, Lucio; Gobbi, Giuseppe; Minetti, Carlo; Nicita, Francesco; Parisi, Pasquale; Pavone, Piero; Pezzella, Marianna; Sesta, Michela; Spalice, Alberto; Striano, Salvatore; Tozzi, Elisabetta; Traverso, Monica; Vari, Stella; Vignoli, Aglaia; Zamponi, Nelia; Zara, Federico; Striano, Pasquale; Verrotti, Alberto

    2013-10-01

    To investigate whether patients with typical absence seizures (TAS) starting in the first 3 years of life, conformed to Panayiotopoulos's definition of childhood absence epilepsy (CAE), show different electroclinical course than those not fulfilling CAE criteria. In this multicenter retrospective study, we choose a fixed duration follow-up of 36 months to examine the electroclinical course of epilepsy in all children with TAS starting before 3 years of age. The probands who fulfilled Panayiotopoulos's criteria for CAE were classified as having pure early onset absence epilepsy (P-EOAE), whereas those who did not as nonpure EOAE (NP-EOAE). In addition, these two groups of patients were further stratified according to the number of antiepileptic drugs taken to obtain initial seizure control (mono-, bi-, and tritherapy). Patients with P-EOAE (n = 111) showed earlier initial seizure control (p = 0.030) and better seizure-free survival curve (p = 0.004) than those with NP-EOAE (n = 77). No mutation in SLC2A1 gene or abnormal neuroimaging was observed in P-EOAE. Among patients with NP-EOAE, those receiving tritherapy showed increased risk of structural brain abnormalities (p = 0.001) or SLC2A1 mutations (p = 0.001) but fewer myoclonic features (p = 0.031) and worse seizure-free survival curve (p = 0.047) than those treated with mono- and bitherapy. Children with NP-EOAE had 2.134 the odds of having relapse during the follow-up compare to those with P-EOAE. Children with early onset TAS who did meet Panayiotopoulos's criteria showed a favorable course of epilepsy, whereas patients not fulfilling Panayiotopoulos's criteria showed increased risk of relapse at long-term follow-up. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

  10. Bone mineral density in partially recovered early onset anorexic patients - a follow-up investigation

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    Schneider Peter

    2010-07-01

    Full Text Available Abstract Background and aims There still is a lack of prospective studies on bone mineral development in patients with a history of early onset Anorexia nervosa (AN. Therefore we assessed associations between bone mass accrual and clinical outcomes in a former clinical sample. In addition to an expected influence of regular physical activity and hormone replacement therapy, we explored correlations with nutritionally dependent hormones. Methods 3-9 years (mean 5.2 ± 1.7 after hospital discharge, we re-investigated 52 female subjects with a history of early onset AN. By means of a standardized approach, we evaluated the general outcome of AN. Moreover, bone mineral content (BMC and bone mineral density (BMD as well as lean and fat mass were measured by dual-energy x-ray absorptiometry (DXA. In a substudy, we measured the serum concentrations of leptin and insulin-like growth factor-I (IGF-I. Results The general outcome of anorexia nervosa was good in 50% of the subjects (BMI ≥ 17.5 kg/m2, resumption of menses. Clinical improvement was correlated with BMC and BMD accrual (χ2 = 5.62/χ2 = 6.65, p = 0.06 / p = 0.036. The duration of amenorrhea had a negative correlation with BMD (r = -.362; p th percentile. IGF-I serum concentrations corresponded to the general outcome of AN. By contrast, leptin serum concentrations showed great variability. They correlated with BMC and current body composition parameters. Conclusions Our results from the main study indicate a certain adaptability of bone mineral accrual which is dependent on a speedy and ongoing recovery. While leptin levels in the substudy tended to respond immediately to current nutritional status, IGF-I serum concentrations corresponded to the individual's age and general outcome of AN.

  11. Omega-3 fatty acids and the genetic risk of early onset acute coronary syndrome.

    Science.gov (United States)

    Leung Yinko, S S L; Thanassoulis, G; Stark, K D; Avgil Tsadok, M; Engert, J C; Pilote, L

    2014-11-01

    Recent gene-environment interaction studies suggest that diet may influence an individual's genetic predisposition to cardiovascular risk. We evaluated whether omega-3 fatty acid intake may influence the risk for acute coronary syndrome (ACS) conferred by genetic polymorphisms among patients with early onset ACS. Our population consisted of 705 patients of white European descent enrolled in GENESIS-PRAXY, a multicenter cohort study of patients aged 18-55 years and hospitalized with ACS. We used a case-only design to investigate interactions between the omega-3 index (a validated biomarker of omega-3 fatty acid intake) and 30 single nucleotide polymorphisms (SNPs) robustly associated with ACS. We used logistic regression to assess the interaction between each SNP and the omega-3 index. Interaction was also assessed between the omega-3 index and a genetic risk score generated from the 30 SNPs. All models were adjusted for age and sex. An interaction for increased ACS risk was found between carriers of the chromosome 9p21 variant rs4977574 and low omega-3 index (OR 1.57, 95% CI 1.07-2.32, p = 0.02), but this was not significant after correction for multiple testing. Similar results were obtained in the adjusted model (OR 1.55, 95% CI 1.05-2.29, p = 0.03). We did not observe any interaction between the genetic risk score or any of the other SNPs and the omega-3 index. Our results suggest that omega-3 fatty acid intake may modify the genetic risk conferred by chromosome 9p21 variation in the development of early onset ACS and requires independent replication. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Epidemiology of early-onset dementia: a review of the literature

    Science.gov (United States)

    Vieira, Renata Teles; Caixeta, Leonardo; Machado, Sergio; Silva, Adriana Cardoso; Nardi, Antonio Egidio; Arias-Carrión, Oscar; Carta, Mauro Giovanni

    2013-01-01

    Presenile Dementia or Early Onset Dementia (EOD) is a public health problem, it differs from Senile Dementia, and encloses a significant number of cases; nevertheless, it is still poorly understood and underdiagnosed. This study aims to review the prevalence and etiology of EOD, comparing EOD with Senile Dementia, as well as to show the main causes of EOD and their prevalence in population and non-population based studies. The computer-supported search used the following databases: Pubmed/Medline, ISI Web of Knowledge and Scielo. The search terms were alcohol-associated dementia, Alzheimer’s disease, dementia, Creutzfeldt-jakob disease, dementia with lewy bodies, early onset dementia, frontotemporal lobar degeneration, Huntington’s disease, mixed dementia, neurodegenerative disorders, Parkinson’s disease dementia, presenile dementia, traumatic brain injury, vascular dementia. Only papers published in English and conducted from 1985 up to 2012 were preferentially reviewed. Neurodegenerative diseases are the most common etiologies seen in EOD. Among the general population, the prevalence of EOD was found to range between 0 to 700 per 100.000 habitants in groups of 25-64 years old, with an increasing incidence with age. The progression of EOD was found to range between 8.3 to 22.8 new cases per 100.000 in those aged under 65 years. Alzheimer's disease (AD) is the major etiology, followed by Vascular Dementia (VaD) and Frontotemporal Lobar Degeneration (FTLD). A larger number of epidemiological studies to elucidate how environmental issues contribute to EOD are necessary, thus, we can collaborate in the planning and prevention of services toward dementia patients. PMID:23878613

  13. Early-Onset Thrombocytopenia in Small-For-Gestational-Age Neonates: A Retrospective Cohort Study.

    Directory of Open Access Journals (Sweden)

    S F Fustolo-Gunnink

    Full Text Available Thrombocytopenia is a common finding in small for gestational age (SGA neonates and is thought to result from a unique pathophysiologic mechanism related to chronic intrauterine hypoxia. Our objective was to estimate the incidence and severity of early-onset thrombocytopenia in SGA neonates, and to identify risk factors for thrombocytopenia. We performed a retrospective cohort study of all consecutive SGA neonates admitted to our ward and a control group of appropriate for gestational age (AGA neonates matched for gestational age at birth. Main outcome measures were incidence and severity of thrombocytopenia, hematological and clinical risk factors for thrombocytopenia, and bleeding. A total of 330 SGA and 330 AGA neonates were included, with a mean gestational age at birth of 32.9 ± 4 weeks. Thrombocytopenia (<150x109/L was found in 53% (176/329 of SGA neonates and 20% (66/330 of AGA neonates (relative risk (RR 2.7, 95% confidence interval (CI [2.1, 3.4]. Severe thrombocytopenia (21-50x109/L occurred in 25 neonates (8% in the SGA and 2 neonates (1% in the AGA group (RR 12.5, 95% CI [3.0, 52.5]. Platelet counts <20x109/L were not recorded. Within the SGA group, lower gestational age at birth (p = <0.01 and erythroblastosis (p<0.01 were independently associated with a decrease in platelet count. Platelet count was positively correlated with birth weight centiles. In conclusion, early-onset thrombocytopenia is present in over 50% of SGA neonates and occurs 2.7 times as often as in AGA neonates. Thrombocytopenia is seldom severe and is independently associated with lower gestational age at birth and erythroblastosis.

  14. Reproduction and Growth in a Murine Model of Early Life-Onset Inflammatory Bowel Disease.

    Directory of Open Access Journals (Sweden)

    Eniko Nagy

    Full Text Available Studies in transgenic murine models have provided insight into the complexity underlying inflammatory bowel disease (IBD, a disease hypothesized to result from an injurious immune response against intestinal microbiota. We recently developed a mouse model of IBD that phenotypically and histologically resembles human childhood-onset ulcerative colitis (UC, using mice that are genetically modified to be deficient in the cytokines TNF and IL-10 ("T/I" mice. Here we report the effects of early life onset of colon inflammation on growth and reproductive performance of T/I mice. T/I dams with colitis often failed to get pregnant or had small litters with pups that failed to thrive. Production was optimized by breeding double homozygous mutant T/I males to females homozygous mutant for TNF deficiency and heterozygous for deficiency of IL-10 ("T/I-het" dams that were not susceptible to spontaneous colon inflammation. When born to healthy (T/I-het dams, T/I pups initially gained weight similarly to wild type (WT pups and to their non-colitis-susceptible T/I-het littermates. However, their growth curves diverged between 8 and 13 weeks, when most T/I mice had developed moderate to severe colitis. The observed growth failure in T/I mice occurred despite a significant increase in their food consumption and in the absence of protein loss in the stool. This was not due to TNF-induced anorexia or altered food consumption due to elevated leptin levels. Metabolic studies demonstrated increased consumption of oxygen and water and increased production of heat and CO2 in T/I mice compared to their T/I-het littermates, without differences in motor activity. Based on the clinical similarities of this early life onset model of IBD in T/I mice to human IBD, these results suggest that mechanisms previously hypothesized to explain growth failure in children with IBD require re-evaluation. The T/I mouse model may be useful for further investigation of such mechanisms and

  15. Molecular Diagnostics of Copper-Transporting Protein Mutations Allows Early Onset Individual Therapy of Menkes Disease.

    Science.gov (United States)

    Králík, L; Flachsová, E; Hansíková, H; Saudek, V; Zeman, J; Martásek, P

    2017-01-01

    Menkes disease is a severe X-linked recessive disorder caused by a defect in the ATP7A gene, which encodes a membrane copper-transporting ATPase. Deficient activity of the ATP7A protein results in decreased intestinal absorption of copper, low copper level in serum and defective distribution of copper in tissues. The clinical symptoms are caused by decreased activities of copper-dependent enzymes and include neurodegeneration, connective tissue disorders, arterial changes and hair abnormalities. Without therapy, the disease is fatal in early infancy. Rapid diagnosis of Menkes disease and early start of copper therapy is critical for the effectiveness of treatment. We report a molecular biology-based strategy that allows early diagnosis of copper transport defects and implementation of individual therapies before the full development of pathological symptoms. Low serum copper and decreased activity of copperdependent mitochondrial cytochrome c oxidase in isolated platelets found in three patients indicated a possibility of functional defects in copper-transporting proteins, especially in the ATPA7 protein, a copper- transporting P-type ATPase. Rapid mutational screening of the ATP7A gene using high-resolution melting analysis of DNA indicated presence of mutations in the patients. Molecular investigation for mutations in the ATP7A gene revealed three nonsense mutations: c.2170C>T (p.Gln724Ter); c.3745G>T (p.Glu1249Ter); and c.3862C>T (p.Gln1288Ter). The mutation c.3745G>T (p.Glu1249Ter) has not been identified previously. Molecular analysis of the ATOX1 gene as a possible modulating factor of Menkes disease did not reveal presence of pathogenic mutations. Molecular diagnostics allowed early onset of individual therapies, adequate genetic counselling and prenatal diagnosis in the affected families.

  16. Evaluation of common genetic variants identified by GWAS for early onset and morbid obesity in population-based samples

    DEFF Research Database (Denmark)

    den Hoed, M; Luan, J; Langenberg, C

    2013-01-01

    BACKGROUND: Meta-analysis of case-control genome-wide association studies (GWAS) for early onset and morbid obesity identified four variants in/near the PRL, PTER, MAF and NPC1 genes. OBJECTIVE: We aimed to validate association of these variants with obesity-related traits in population-based sam......BACKGROUND: Meta-analysis of case-control genome-wide association studies (GWAS) for early onset and morbid obesity identified four variants in/near the PRL, PTER, MAF and NPC1 genes. OBJECTIVE: We aimed to validate association of these variants with obesity-related traits in population......, these variants, which were identified in a GWAS for early onset and morbid obesity, do not seem to influence obesity-related traits in the general population....

  17. A Novel TTBK2 De Novo Mutation in a Danish Family with Early-Onset Spinocerebellar Ataxia

    DEFF Research Database (Denmark)

    Lindquist, Suzanne Granhøj; Møller, Lisbeth Birk; Dali, Christine I.

    2017-01-01

    Spinocerebellar ataxia type 11 (SCA11) is rare and has previously been described in four families worldwide. We report a Danish family with onset of symptoms in early childhood and affected family members in two generations. The proband, a Danish female born in 1968, and family members were...... examined. Exome sequencing was performed and a “movement disorders” gene panel consisting of approximately 200 genes was used for filtering, while Sanger sequencing was used for subsequent testing for the mutation in the family. Onset of symptoms in affected family members was in early childhood. A novel...... delineates the phenotypic spectrum of the rare SCA11 disease. In contrast to previously reported cases, onset of symptoms was in early childhood and the mutation was de novo in the proband....

  18. Early onset of industrial-era warming across the oceans and continents.

    Science.gov (United States)

    Abram, Nerilie J; McGregor, Helen V; Tierney, Jessica E; Evans, Michael N; McKay, Nicholas P; Kaufman, Darrell S

    2016-08-25

    The evolution of industrial-era warming across the continents and oceans provides a context for future climate change and is important for determining climate sensitivity and the processes that control regional warming. Here we use post-ad 1500 palaeoclimate records to show that sustained industrial-era warming of the tropical oceans first developed during the mid-nineteenth century and was nearly synchronous with Northern Hemisphere continental warming. The early onset of sustained, significant warming in palaeoclimate records and model simulations suggests that greenhouse forcing of industrial-era warming commenced as early as the mid-nineteenth century and included an enhanced equatorial ocean response mechanism. The development of Southern Hemisphere warming is delayed in reconstructions, but this apparent delay is not reproduced in climate simulations. Our findings imply that instrumental records are too short to comprehensively assess anthropogenic climate change and that, in some regions, about 180 years of industrial-era warming has already caused surface temperatures to emerge above pre-industrial values, even when taking natural variability into account.

  19. The onset of the Early Eocene Climatic Optimum at Branch Stream, Clarence River valley, New Zealand

    International Nuclear Information System (INIS)

    Slotnick, B.S.; Dickens, G.R.; Hollis, C.J.; Crampton, J.S.; Strong, C.P.; Phillips, A.

    2015-01-01

    We present new lithologic, biostratigraphic and carbon isotope records for a calcareous-rich ∼84m thick, early Eocene, upper continental slope section now exposed along Branch Stream, Marlborough. Decimetre-scale limestone-marl couplets comprise the section. Several marl-rich intervals correspond to carbon isotope excursions (CIEs) representing increased 13 C -depleted carbon fluxes to the ocean. These records are similar to those at nearby Mead Stream, except marl-rich intervals at Branch Stream are thicker with a wider δ 13 C range. Comparison to other sites indicates the section spans ∼53.4-51.6 Ma, the onset of the Early Eocene Climatic Optimum (EECO). The most prominent CIE is correlated with the K/X event (52.9 Ma). Prominent marl-rich intervals resulted from increased fluxes of terrigenous material and associated carbonate dilution. We find multiple warming events marked lowermost EECO, each probably signaling enhanced seasonal precipitation. Branch Stream bulk isotopic records suggest 'differential diagenesis' impacted the sequence during sediment burial. (author).

  20. Early onset polymyalgia rheumatica: two rare cases under age of 50

    International Nuclear Information System (INIS)

    Park, Jinyoung; Sung, Duk Hyun

    2017-01-01

    Polymyalgia rheumatica (PMR) is almost an exclusive disease of adults over the age of 50, and only a few cases have been reported. Two 46-year-old females visited our locomotor pain clinic with multiple joint pain with increased acute phase reactants. Rheumatologic markers, and HLA-B27 were checked. Serum protein electrophoresis and serum immunofixation electrophoresis, imaging studies including plane image, sonography, and magnetic resonance image was done. "1"8F-Fludeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) showed characteristic findings of PMR, without evidences of sacroiliitis. Since PMR can develop in mid 40s, a high index of suspicion is necessary in younger patients presenting the bilateral pain in shoulders, hips, and back, with elevated acute phase reactants. Furthermore, in addition to the previous case reports, FDG-PET/CT is helpful in making early differential diagnosis of PMR in patients under the age of 50. Here we present two cases of PMR onset in the mid-40s emphasizing the importance of diagnostic imaging for early differential diagnosis in PMR. (orig.)

  1. Early onset polymyalgia rheumatica: two rare cases under age of 50

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jinyoung [Yonsei University College of Medicine, Department of Rehabilitation Medicine, Gangnam Severance Hospital, Rehabilitation Institute of Neuromuscular Disease, Seoul (Korea, Republic of); Sung, Duk Hyun [Samsung Medical Center, Department of Physical and Rehabilitation Medicine, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul (Korea, Republic of)

    2017-06-15

    Polymyalgia rheumatica (PMR) is almost an exclusive disease of adults over the age of 50, and only a few cases have been reported. Two 46-year-old females visited our locomotor pain clinic with multiple joint pain with increased acute phase reactants. Rheumatologic markers, and HLA-B27 were checked. Serum protein electrophoresis and serum immunofixation electrophoresis, imaging studies including plane image, sonography, and magnetic resonance image was done. {sup 18}F-Fludeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) showed characteristic findings of PMR, without evidences of sacroiliitis. Since PMR can develop in mid 40s, a high index of suspicion is necessary in younger patients presenting the bilateral pain in shoulders, hips, and back, with elevated acute phase reactants. Furthermore, in addition to the previous case reports, FDG-PET/CT is helpful in making early differential diagnosis of PMR in patients under the age of 50. Here we present two cases of PMR onset in the mid-40s emphasizing the importance of diagnostic imaging for early differential diagnosis in PMR. (orig.)

  2. Successful Object Encoding Induces Increased Directed Connectivity in Presymptomatic Early-Onset Alzheimer’s Disease

    Science.gov (United States)

    Ochoa, John Fredy; Alonso, Joan Francesc; Duque, Jon Edinson; Tobón, Carlos Andrés; Mañanas, Miguel Angel; Lopera, Francisco; Hernández, Alher Mauricio

    2016-01-01

    Background: Recent studies report increases in neural activity in brain regions critical to episodic memory at preclinical stages of Alzheimer’s disease (AD). Although electroencephalography (EEG) is widely used in AD studies, given its non-invasiveness and low cost, there is a need to translate the findings in other neuroimaging methods to EEG. Objective: To examine how the previous findings using functional magnetic resonance imaging (fMRI) at preclinical stage in presenilin-1 E280A mutation carriers could be assessed and extended, using EEG and a connectivity approach. Methods: EEG signals were acquired during resting and encoding in 30 normal cognitive young subjects, from an autosomal dominant early-onset AD kindred from Antioquia, Colombia. Regions of the brain previously reported as hyperactive were used for connectivity analysis. Results: Mutation carriers exhibited increasing connectivity at analyzed regions. Among them, the right precuneus exhibited the highest changes in connectivity. Conclusion: Increased connectivity in hyperactive cerebral regions is seen in individuals, genetically-determined to develop AD, at preclinical stage. The use of a connectivity approach and a widely available neuroimaging technique opens the possibility to increase the use of EEG in early detection of preclinical AD. PMID:27792014

  3. Similarities and differences between infantile and early childhood onset vanishing white matter disease.

    Science.gov (United States)

    Zhou, Ling; Zhang, Haihua; Chen, Na; Zhang, Zhongbin; Liu, Ming; Dai, Lifang; Wang, Jingmin; Jiang, Yuwu; Wu, Ye

    2018-06-01

    Vanishing white matter disease (VWM) is one of the most prevalent inherited leukoencephalopathies in childhood. Infantile VWM is more severe but less understood than the classic early childhood type. We performed a follow-up study on 14 infantile and 26 childhood patients to delineate the natural history and neuroimaging features of VWM. Infantile and childhood patients shared similarities in the incidence of epileptic seizure (35.7 vs. 38.5%) and episodic aggravation (92.9 vs. 84.6%). Developmental delay before disease onset was more common in infantile patients. Motor disability was earlier and more severe in infantile VWM. In survivors with disease durations of 1-3 years, the Gross Motor Function Classification System (GMFCS) was classified as IV-V in 66.7% of infantile and only 29.4% of childhood patients. Kaplan-Meier survival curve analysis indicated that the 5-year survival rates were 21.6 and 91.3% in infantile and childhood VWM, respectively. In terms of MRI, infantile patients showed more extensive involvement and earlier rarefaction, with more common involvement of subcortical white matter, internal capsule, brain stem and dentate nuclei of the cerebellum. Restricted diffusion was more diffuse or extensive in infantile patients. In addition, four novel mutations were identified. In conclusion, we identified some similarities and differences in the natural history and neuroimaging features between infantile and early childhood VWM.

  4. Early onset intellectual disability in chromosome 22q11.2 deletion syndrome.

    Science.gov (United States)

    Cascella, Marco; Muzio, Maria Rosaria

    2015-01-01

    Chromosome 22q11.2 deletion syndrome, or DiGeorge syndrome, or velocardiofacial syndrome, is one of the most common multiple anomaly syndromes in humans. This syndrome is commonly caused by a microdelection from chromosome 22 at band q11.2. Although this genetic disorder may reflect several clinical abnormalities and different degrees of organ commitment, the clinical features that have driven the greatest amount of attention are behavioral and developmental features, because individuals with 22q11.2 deletion syndrome have a 30-fold risk of developing schizophrenia. There are differing opinions about the cognitive development, and commonly a cognitive decline rather than an early onset intellectual disability has been observed. We report a case of 22q11.2 deletion syndrome with both early assessment of mild intellectual disabilities and tetralogy of Fallot as the only physic manifestation. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. Newcomers in paediatric GI pathology: childhood enteropathies including very early onset monogenic IBD.

    Science.gov (United States)

    Ensari, Arzu; Kelsen, Judith; Russo, Pierre

    2018-01-01

    Childhood enteropathies are a group of diseases causing severe chronic (>2-3 weeks) diarrhoea often starting in the first week of life with the potential for fatal complications for the affected infant. Early identification and accurate classification of childhood enteropathies are, therefore, crucial for making treatment decisions to prevent life-threatening complications. Childhood enteropathies are classified into four groups based on the underlying pathology: (i) conditions related to defective digestion, absorption and transport of nutrients and electrolytes; (ii) disorders related to enterocyte differentiation and polarization; (iii) defects of enteroendocrine cell differentiation; and (iv) disorders associated with defective modulation of intestinal immune response. While the intestinal mucosa is usually normal in enteropathies related to congenital transport or enzyme deficiencies, the intestinal biopsy in other disorders may reveal a wide range of abnormalities varying from normal villous architecture to villous atrophy and/or inflammation, or features specific to the underlying disorder including epithelial abnormalities, lipid vacuolization in the enterocytes, absence of plasma cells, lymphangiectasia, microorganisms, and mucosal eosinophilic or histiocytic infiltration. This review intends to provide an update on small intestinal biopsy findings in childhood enteropathies, the "newcomers", including very early onset monogenic inflammatory bowel disease (IBD), in particular, for the practicing pathologist.

  6. Distinct high resolution genome profiles of early onset and late onset colorectal cancer integrated with gene expression data identify candidate susceptibility loci

    Directory of Open Access Journals (Sweden)

    Merok Marianne A

    2010-05-01

    Full Text Available Abstract Background Estimates suggest that up to 30% of colorectal cancers (CRC may develop due to an increased genetic risk. The mean age at diagnosis for CRC is about 70 years. Time of disease onset 20 years younger than the mean age is assumed to be indicative of genetic susceptibility. We have compared high resolution tumor genome copy number variation (CNV (Roche NimbleGen, 385 000 oligo CGH array in microsatellite stable (MSS tumors from two age groups, including 23 young at onset patients without known hereditary syndromes and with a median age of 44 years (range: 28-53 and 17 elderly patients with median age 79 years (range: 69-87. Our aim was to identify differences in the tumor genomes between these groups and pinpoint potential susceptibility loci. Integration analysis of CNV and genome wide mRNA expression data, available for the same tumors, was performed to identify a restricted candidate gene list. Results The total fraction of the genome with aberrant copy number, the overall genomic profile and the TP53 mutation spectrum were similar between the two age groups. However, both the number of chromosomal aberrations and the number of breakpoints differed significantly between the groups. Gains of 2q35, 10q21.3-22.1, 10q22.3 and 19q13.2-13.31 and losses from 1p31.3, 1q21.1, 2q21.2, 4p16.1-q28.3, 10p11.1 and 19p12, positions that in total contain more than 500 genes, were found significantly more often in the early onset group as compared to the late onset group. Integration analysis revealed a covariation of DNA copy number at these sites and mRNA expression for 107 of the genes. Seven of these genes, CLC, EIF4E, LTBP4, PLA2G12A, PPAT, RG9MTD2, and ZNF574, had significantly different mRNA expression comparing median expression levels across the transcriptome between the two groups. Conclusions Ten genomic loci, containing more than 500 protein coding genes, are identified as more often altered in tumors from early onset versus late

  7. Childhood abuse and late-life depression: Mediating effects of psychosocial factors for early- and late-onset depression.

    Science.gov (United States)

    Wielaard, Ilse; Hoyer, Mathijs; Rhebergen, Didi; Stek, Max L; Comijs, Hannie C

    2018-03-01

    Childhood abuse makes people vulnerable to developing depression, even in late life. Psychosocial factors that are common in late life, such as loneliness or lack of a partner, may explain this association. Our aim was to investigate whether the association between childhood abuse and depression in older adults can be explained by psychosocial factors. Cross-sectional data were derived from the Netherlands Study of Depression in Older Persons (aged 60-93), including 132 without lifetime depression, 242 persons with an early-onset depression (Childhood abuse (yes/no) and a frequency-based childhood abuse index were included. Multinomial regression and multivariable mediation analyses were used to examine the association between childhood abuse and the onset of depression, and the influence of loneliness, social network, and partner status. Multinomial regression analyses showed a significant association between childhood abuse and the childhood abuse index with early- and late-onset depression. Multivariable mediation analyses showed that the association between childhood abuse and early-onset depression was partly mediated by social network size and loneliness. This was particularly present for emotional neglect and psychological abuse, but not for physical and sexual abuse. No psychosocial mediators were found for the association between childhood abuse and late-onset depression. A smaller social network and feelings of loneliness mediate the association between childhood abuse and early-onset depression in older adults. Our findings show the importance of detecting childhood abuse as well as the age at depression onset and mapping of relevant psychosocial factors in the treatment of late-life depression. Copyright © 2018 John Wiley & Sons, Ltd.

  8. Thyroid peroxidase antibodies during early gestation and the subsequent risk of first-onset postpartum depression: A prospective cohort study.

    Science.gov (United States)

    Wesseloo, Richard; Kamperman, Astrid M; Bergink, Veerle; Pop, Victor J M

    2018-01-01

    During the postpartum period, women are at risk for the new onset of both auto-immune thyroid disorders and depression. The presence of thyroid peroxidase antibodies (TPO-ab) during early gestation is predictive for postpartum auto-immune thyroid dysfunction. The aim of this study was to investigate the association between TPO-ab status during early gestation and first-onset postpartum depression. Prospective cohort study (n = 1075) with follow-up during pregnancy up to one year postpartum. Thyroid function and TPO-ab status were measured during early gestation. Depressive symptomatology was assessed during each trimester and at four time points postpartum with the Edinburgh Depression Scale (EDS). Women with antenatal depression were not eligible for inclusion. Self-reported postpartum depression was defined with an EDS cut-off of ≥ 13. The cumulative incidence of self-reported first-onset depression in the first postpartum year was 6.3%. A positive TPO-ab status was associated with an increased risk for self-reported first-onset depression at four months postpartum (adjusted OR 3.8; 95% CI 1.3-11.6), but not at other postpartum time points. Prevalence rates of self-reported postpartum depression declined after four months postpartum in the TPO-ab positive group, but remained constant in the TPO-ab negative group. Depression was defined with a self-rating questionnaire (EDS). Women with an increased TPO-ab titer during early gestation are at increased risk for self-reported first-onset depression. The longitudinal pattern of self-reported postpartum depression in the TPO-ab positive group was similar to the typical course of postpartum TPO-ab titers changes. This suggests overlap in the etiology of first-onset postpartum depression and auto-immune thyroid dysfunction. Thyroid function should be evaluated in women with first-onset postpartum depression. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. MMP-15 is upregulated in preeclampsia, but does not cleave endoglin to produce soluble endoglin.

    Directory of Open Access Journals (Sweden)

    Tu'uhevaha J Kaitu'u-Lino

    Full Text Available Preeclampsia is a major pregnancy complication, characterized by severe endothelial dysfunction, hypertension and maternal end-organ damage. Soluble endoglin is an anti-angiogenic protein released from placenta and thought to play a central role in causing the endothelial dysfunction and maternal organ injury seen in severe preeclampsia. We recently reported MMP-14 was the protease producing placentally-derived soluble endoglin by cleaving full-length endoglin present on the syncytiotrophoblast surface. This find identifies a specific drug target for severe preeclampsia; interfering with MMP-14 mediated cleavage of endoglin could decrease soluble endoglin production, ameliorating clinical disease. However, experimental MMP-14 inhibition alone only partially repressed soluble endoglin production, implying other proteases might have a role in producing soluble endoglin. Here we investigated whether MMP-15--phylogenetically the closest MMP relative to MMP-14 with 66% sequence similarity--also cleaves endoglin to produce soluble endoglin. MMP-15 was localized to the syncytiotrophoblast layer of the placenta, the same site where endoglin was localized. Interestingly, it was significantly (p = 0.03 up-regulated in placentas from severe early-onset preeclamptic pregnancies (n = 8 compared to gestationally matched preterm controls (n = 8. However, siRNA knockdown of MMP-15 yielded no significant decrease of soluble endoglin production from either HUVECs or syncytialised BeWo cells in vitro. Importantly, concurrent siRNA knockdown of both MMP-14 and MMP-15 in HUVECS did not yield further decrease in soluble endoglin production compared to MMP-14 siRNA alone. We conclude MMP-15 is up-regulated in preeclampsia, but does not cleave endoglin to produce soluble endoglin.

  10. Early onset ageing and service preparation in people with intellectual disabilities: institutional managers' perspective.

    Science.gov (United States)

    Lin, Jin-Ding; Wu, Chia-Ling; Lin, Pei-Ying; Lin, Lan-Ping; Chu, Cordia M

    2011-01-01

    Although longevity among older adults with intellectual disabilities is increasing, there is limited information on their premature aging related health characteristics and how it may change with increasing age. The present paper provides information of the institutional manager's perception on early onset aging and service preparation for this population. We used purposive sampling to recruit 54 institutional managers who care for people with intellectual disabilities in Taiwan. The present study employed a cross-sectional design using a self-administrative structured questionnaire that was completed by the respondents in November 2009. The results showed that more than 90% of the respondents agreed with earlier onset aging characteristics of people with ID. However, nearly all of the respondents expressed that the government policies were inadequate and the institution is not capable of caring for aging people with ID, and more than half of them did not satisfy to their provisional care for this group of people. With regard to the service priority of government aging policy for people with ID, the respondent expressed that medical care, financial support, daily living care were the main areas in the future policy development for them. The factors of institutional type, expressed adequacy of government's service, respondent's job position, age, and working years in disability service were variables that can significantly predict the positive perceptions toward future governmental aging services for people with ID (adjusted R(2) = 0.563). We suggest that the future study strategy should underpin the aging characteristics of people with intellectual disabilities and its differences with general population to provide the useful information for the institutional caregivers. Copyright © 2010 Elsevier Ltd. All rights reserved.

  11. Low Prevalence and Clinical Effect of Vascular Risk Factors in Early-Onset Alzheimer's Disease.

    Science.gov (United States)

    Chen, Yaohua; Sillaire, Adeline Rollin; Dallongeville, Jean; Skrobala, Emilie; Wallon, David; Dubois, Bruno; Hannequin, Didier; Pasquier, Florence

    2017-01-01

    Determinants of early-onset Alzheimer's disease (EOAD) are not well known. In late-onset AD, vascular risk factors (VRFs) are associated with earlier clinical manifestation. The objective of this study was to assess the putative association between VRFs and EOAD. We studied participants with dementia meeting criteria for EOAD (recruited into the French CoMAJ prospective cohort study from 1 June 2009 to 28 February 2014) and age-, gender-matched controls (ratio 1:3, drawn randomly from the French MONA-LISA population-based survey between 2005 and 2007). Demographic data, VRFs, comorbidities, treatments, and APOE genotypes were compared in multivariable logistic regression analyses. We studied 102 participants with dementia (mean±standard deviation age: 59.5±3.8; women: 59.8%) and 306 controls. Compared with controls, EOAD participants had spent less time in formal education (9.9±2.9 versus 11.7±3.8 y; p < 0.0001), were less likely to be regular alcohol consumers (p < 0.0001), had a lower body mass index (-2 kg/m2; p < 0.0004), and a lower mean systolic blood pressure (-6.2 mmHg; p = 0.0036). The prevalence of APOE ɛ4 allele was higher in participants with dementia than in controls (50% versus 29.4%; p = 0.0002), as was the prevalence of depression (48% versus 32%; p < 0.001). Similar results were observed in multivariable analysis. Compared with EOAD participants lacking VRFs, EOAD participants with at least one VRF had a higher prevalence of depression (29.6% versus 53.3%, respectively; p = 0.03). The prevalence of VRFs is not elevated in EOAD patients (in contrast to older AD patients). Extensive genetic testing should be considered more frequently in the context of EOAD.

  12. Deleterious ABCA7 mutations and transcript rescue mechanisms in early onset Alzheimer's disease.

    Science.gov (United States)

    De Roeck, Arne; Van den Bossche, Tobi; van der Zee, Julie; Verheijen, Jan; De Coster, Wouter; Van Dongen, Jasper; Dillen, Lubina; Baradaran-Heravi, Yalda; Heeman, Bavo; Sanchez-Valle, Raquel; Lladó, Albert; Nacmias, Benedetta; Sorbi, Sandro; Gelpi, Ellen; Grau-Rivera, Oriol; Gómez-Tortosa, Estrella; Pastor, Pau; Ortega-Cubero, Sara; Pastor, Maria A; Graff, Caroline; Thonberg, Håkan; Benussi, Luisa; Ghidoni, Roberta; Binetti, Giuliano; de Mendonça, Alexandre; Martins, Madalena; Borroni, Barbara; Padovani, Alessandro; Almeida, Maria Rosário; Santana, Isabel; Diehl-Schmid, Janine; Alexopoulos, Panagiotis; Clarimon, Jordi; Lleó, Alberto; Fortea, Juan; Tsolaki, Magda; Koutroumani, Maria; Matěj, Radoslav; Rohan, Zdenek; De Deyn, Peter; Engelborghs, Sebastiaan; Cras, Patrick; Van Broeckhoven, Christine; Sleegers, Kristel

    2017-09-01

    Premature termination codon (PTC) mutations in the ATP-Binding Cassette, Sub-Family A, Member 7 gene (ABCA7) have recently been identified as intermediate-to-high penetrant risk factor for late-onset Alzheimer's disease (LOAD). High variability, however, is observed in downstream ABCA7 mRNA and protein expression, disease penetrance, and onset age, indicative of unknown modifying factors. Here, we investigated the prevalence and disease penetrance of ABCA7 PTC mutations in a large early onset AD (EOAD)-control cohort, and examined the effect on transcript level with comprehensive third-generation long-read sequencing. We characterized the ABCA7 coding sequence with next-generation sequencing in 928 EOAD patients and 980 matched control individuals. With MetaSKAT rare variant association analysis, we observed a fivefold enrichment (p = 0.0004) of PTC mutations in EOAD patients (3%) versus controls (0.6%). Ten novel PTC mutations were only observed in patients, and PTC mutation carriers in general had an increased familial AD load. In addition, we observed nominal risk reducing trends for three common coding variants. Seven PTC mutations were further analyzed using targeted long-read cDNA sequencing on an Oxford Nanopore MinION platform. PTC-containing transcripts for each investigated PTC mutation were observed at varying proportion (5-41% of the total read count), implying incomplete nonsense-mediated mRNA decay (NMD). Furthermore, we distinguished and phased several previously unknown alternative splicing events (up to 30% of transcripts). In conjunction with PTC mutations, several of these novel ABCA7 isoforms have the potential to rescue deleterious PTC effects. In conclusion, ABCA7 PTC mutations play a substantial role in EOAD, warranting genetic screening of ABCA7 in genetically unexplained patients. Long-read cDNA sequencing revealed both varying degrees of NMD and transcript-modifying events, which may influence ABCA7 dosage, disease severity, and may

  13. Preeclampsia and breast cancer

    DEFF Research Database (Denmark)

    Pacheco, Nadja Livia Pekkola; Andersen, Anne-Marie Nybo; Kamper-Jørgensen, Mads

    2015-01-01

    BACKGROUND: In parous women preeclampsia has been associated with reduced risk of developing breast cancer. Characteristics of births following preeclamptic pregnancies may help understand mechanisms involved in the breast cancer risk reduction inferred by preeclampsia. METHODS: We conducted...... a register-based cohort study of all Danish women giving birth during 1978-2010 (n = 778,701). The association between preeclampsia and breast cancer was evaluated overall and according to birth characteristics by means of incidence rate ratios (IRR) estimated in Poisson regression models. RESULTS: Compared...... with women with non-preeclamptic pregnancies only, women with one or more preeclamptic pregnancies were 19% significantly less likely to develop breast cancer (IRR = 0.81 [95% CI 0.72-0.93]). We found some indication of greater risk reduction in women with term births, one or more previous births...

  14. Why preeclampsia still exists?

    Science.gov (United States)

    Chelbi, Sonia T; Veitia, Reiner A; Vaiman, Daniel

    2013-08-01

    Preeclampsia (PE) is a deadly gestational disease affecting up to 10% of women and specific of the human species. Preeclampsia is clearly multifactorial, but the existence of a genetic basis for this disease is now clearly established by the existence of familial cases, epidemiological studies and known predisposing gene polymorphisms. PE is very common despite the fact that Darwinian pressure should have rapidly eliminated or strongly minimized the frequency of predisposing alleles. Consecutive pregnancies with the same partner decrease the risk and severity of PE. Here, we show that, due to this peculiar feature, preeclampsia predisposing-alleles can be differentially maintained according to the familial structure. Thus, we suggest that an optimal frequency of PE-predisposing alleles in human populations can be achieved as a result of a trade-off between benefits of exogamy, importance for maintaining genetic diversity and increase of the fitness owing to a stable paternal investment. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Blood coagulation parameters and platelet indices: changes in normal and preeclamptic pregnancies and predictive values for preeclampsia.

    Directory of Open Access Journals (Sweden)

    Lei Han

    Full Text Available Preeclampsia (PE is an obstetric disorder with high morbidity and mortality rates but without clear pathogeny. The dysfunction of the blood coagulation-fibrinolysis system is a salient characteristic of PE that varies in severity, and necessitates different treatments. Therefore, it is necessary to find suitable predictors for the onset and severity of PE.We aimed to evaluate blood coagulation parameters and platelet indices as potential predictors for the onset and severity of PE.Blood samples from 3 groups of subjects, normal pregnant women (n = 79, mild preeclampsia (mPE (n = 53 and severe preeclampsia (sPE (n = 42, were collected during early and late pregnancy. The levels of coagulative parameters and platelet indices were measured and compared among the groups. The receiver-operating characteristic (ROC curves of these indices were generated, and the area under the curve (AUC was calculated. The predictive values of the selected potential parameters were examined in binary regression analysis.During late pregnancy in the normal pregnancy group, the activated partial thromboplastin time (APTT, prothrombin time (PT, thrombin time (TT and platelet count decreased, while the fibrinogen level and mean platelet volume (MPV increased compared to early pregnancy (p<0.05. However, the PE patients presented with increased APTT, TT, MPV and D-dimer (DD during the third trimester. In the analysis of subjects with and without PE, TT showed the largest AUC (0.743 and high predictive value. In PE patients with different severities, MPV showed the largest AUC (0.671 and ideal predictive efficiency.Normal pregnancy causes a maternal physiological hypercoagulable state in late pregnancy. PE may trigger complex disorders in the endogenous coagulative pathways and consume platelets and FIB, subsequently activating thrombopoiesis and fibrinolysis. Thrombin time and MPV may serve as early monitoring markers for the onset and severity of PE

  16. Early-life exposures predicting onset and resolution of childhood overweight or obesity.

    Science.gov (United States)

    Kerr, Jessica A; Long, Catherine; Clifford, Susan A; Muller, Joshua; Gillespie, Alanna N; Donath, Susan; Wake, Melissa

    2017-10-01

    To determine which of multiple early-life exposures predict onset or resolution of overweight/obesity during a 9-year period. Design : longitudinal cohort from three harmonised community-based cohorts enriched for overweight and obesity. Early-life exposures : child-gestational age; delivery; birth weight; breast feeding; solids introduction; baseline body mass index (BMI); waist circumference; diet; activity; global, physical and psychosocial health. Mother-baseline BMI; education; age; neighbourhood disadvantage; concern for child's weight. Outcome : change in BMI category. Analyses : adjusted logistic regression. On average, the 363 children (57% retention) were 6 and 15 years old at baseline and follow-up. Children were classified as 'never' overweight/obese (38%), 'resolving' overweight/obese (15%), 'becoming' overweight/obese (8%) or 'always' overweight/obese (39%). Compared with 'never overweight/obese' children, odds of 'becoming overweight/obese' were greater with higher child (OR 2.33, 95% CI 1.02 to 5.29) and maternal BMI (OR 1.18, CI 1.07 to 1.31), and lower with higher maternal education (OR 0.09, CI 0.02 to 0.34). Compared with 'always overweight/obese' children, odds of 'resolving overweight/obese' were lower with higher maternal BMI (OR 0.87, CI 0.78 to 0.97), and higher with better child physical health (OR 1.06, CI 1.02 to 1.10) and higher maternal age (OR 1.11, CI 1.01 to 1.22) and education (OR 4.07, CI 1.02 to 16.19). Readily available baseline information (child/maternal BMI, maternal age, education and child health) were the strongest predictors of both onset and resolution of overweight/obesity between the primary school and adolescent years. Perinatal, breastfeeding and lifestyle exposures were not strongly predictive. Results could stimulate development of algorithms identifying children most in need of targeted prevention or treatment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under

  17. Detorsion night-time bracing for the treatment of early onset idiopathic scoliosis.

    Science.gov (United States)

    Moreau, S; Lonjon, G; Mazda, K; Ilharreborde, B

    2014-12-01

    Management for early onset scoliosis has recently changed, with the development of new surgical procedures. However, multiple surgeries are often required and high complication rates are still reported. Conservative management remains an alternative, serial casting achieving excellent results in young children. Better compliance and improvement over natural history have been reported with night-time bracing in adolescent idiopathic scoliosis (AIS), but this treatment has never been reported in early onset idiopathic scoliosis (EIOS). All patients treated for progressive EOIS by detorsion night-time bracing (DNB), and meeting the Scoliosis Research Society (SRS) criteria for brace studies were reviewed. Recommendations were given to wear the DNB 8h/night and no restriction was given regarding sports activities. Radiological parameters were compared between referral and latest follow-up. Based on the SRS criteria defined for AIS, a similar classification was used as follows to analyze the course of the curves: success group: patients with a progression of 5° or less; unsuccess group (progression or failure): patients with a progression>5°, patients with curves exceeding 45° at maturity, or who have had recommendation for/undergone surgery, or patients who changed orthopaedic treatment, or who were lost to follow-up. Thirty-three patients were included (21 girls and 12 boys), with a median Cobb angle of 31° (Q1-Q3: 22-40). Age at brace initiation averaged 50months (Q1-Q3: 25-60). Median follow-up was 102-months (Q1-Q3: 63-125). Fifteen patients (45.5%) had reached skeletal maturity at last follow-up. The success rate was 67% (22 patients), with a median Cobb angle reduction of 15° (P<0.001). Four patients stopped DNB due to an important regression. Eleven patients were in the unsuccessful group (33%). Only one had surgery. All patients remained balanced in the frontal plane and normokyphotic. Initial curve magnitude and age at brace initiation appeared to be

  18. A novel deleterious PTEN mutation in a patient with early-onset bilateral breast cancer

    International Nuclear Information System (INIS)

    Pradella, Laura Maria; Gasparre, Giuseppe; Turchetti, Daniela; Evangelisti, Cecilia; Ligorio, Claudia; Ceccarelli, Claudio; Neri, Iria; Zuntini, Roberta; Amato, Laura Benedetta; Ferrari, Simona; Martelli, Alberto Maria

    2014-01-01

    An early age at Breast Cancer (BC) onset may be a hallmark of inherited predisposition, but BRCA1/2 mutations are only found in a minority of younger BC patients. Among the others, a fraction may carry mutations in rarer BC genes, such as TP53, STK11, CDH1 and PTEN. As the identification of women harboring such mutations allows for targeted risk-management, the knowledge of associated manifestations and an accurate clinical and family history evaluation are warranted. We describe the case of a woman who developed an infiltrating ductal carcinoma of the right breast at the age of 32, a contralateral BC at age 36 and another BC of the right breast at 40. When she was 39 years-old, during a dermatological examination, mucocutaneous features suggestive of Cowden Syndrome, a disorder associated to germ-line PTEN mutations, were noticed. PTEN genetic testing revealed the novel c.71A > T (p.Asp24Val) mutation, whose deleterious effect, suggested by conservation data and in silico tools, was definitely demonstrated by the incapacity of mutant PTEN to inhibit Akt phosphorylation when used to complement PTEN-null cells. In BC tissue, despite the absence of LOH or somatic mutations of PTEN, Akt phosphorylation was markedly increased in comparison to normal tissue, thus implying additional somatic events into the deregulation of the PI3K/Akt/mTOR pathway and, presumably, into carcinogenesis. Hence, known oncogenic mutations in PIK3CA (exons 10 and 21) and AKT1 (exon 2) were screened in tumor DNA with negative results, which suggests that the responsible somatic event(s) is a different, uncommon one. This case stresses the importance of clinical/genetic assessment of early-onset BC patients in order to identify mutation carriers, who are at high risk of new events, so requiring tailored management. Moreover, it revealed a novel PTEN mutation with pathogenic effect, pointing out, however, the need for further efforts to elucidate the molecular steps of PTEN

  19. Aspiration, Localized Pulmonary Inflammation, and Predictors of Early-Onset Bronchiolitis Obliterans Syndrome after Lung Transplantation

    Science.gov (United States)

    Fisichella, P Marco; Davis, Christopher S; Lowery, Erin; Ramirez, Luis; Gamelli, Richard L; Kovacs, Elizabeth J

    2014-01-01

    BACKGROUND We hypothesized that immune mediator concentrations in the bronchoalveolar fluid (BALF) are predictive of bronchiolitis obliterans syndrome (BOS) and demonstrate specific patterns of dysregulation, depending on the presence of acute cellular rejection, BOS, aspiration, and timing of lung transplantation. STUDY DESIGN We prospectively collected 257 BALF samples from 105 lung transplant recipients. The BALF samples were assessed for absolute and differential white blood cell counts and 34 proteins implicated in pulmonary immunity, inflammation, fibrosis, and aspiration. RESULTS There were elevated BALF concentrations of interleukin (IL)-15, IL-17, basic fibroblast growth factor, tumor necrosis factor–α, and myeloperoxidase, and reduced concentrations of α1-antitrypsin, which were predictive of early-onset BOS. Patients with BOS had an increased percentage of BALF lymphocytes and neutrophils, with a reduced percentage of macrophages (p < 0.05). The BALF concentrations of IL-1β; IL-8; interferon-γ–induced protein 10; regulated upon activation, normal T-cell expressed and secreted; neutrophil elastase; and pepsin were higher in patients with BOS (p < 0.05). Among those with BOS, BALF concentrations of IL-1RA; IL-8; eotaxin; interferon-γ–induced protein 10; regulated upon activation, normal T-cell expressed and secreted; myeloperoxidase; and neutrophil elastase were positively correlated with time since transplantation (p < 0.01). Those with worse grades of acute cellular rejection had an increased percentage of lymphocytes in their BALF (p < 0.0001) and reduced BALF concentrations of IL-1β, IL-7, IL-9, IL-12, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interferon-γ, and vascular endothelial growth factor (p ≤ 0.001). Patients with aspiration based on detectable pepsin had increased percentage of neutrophils (p < 0.001) and reduced BALF concentrations of IL-12 (p < 0.001). CONCLUSIONS The BALF levels

  20. [Genital bacterial carriage during the last trimester of pregnancy and early-onset neonatal sepsis].

    Science.gov (United States)

    Balaka, B; Agbèrè, A; Dagnra, A; Baeta, S; Kessie, K; Assimadi, K

    2005-05-01

    Bacterial infections remain a major cause of morbidity and mortality in newborn infants. To determine the bacterial ecology and pathological status of the genital organs during the last trimester of pregnancy and the germs of the following early-onset neonatal sepsis, in order to evaluate the risk of materno-foetal infections and to find out a drug prophylaxis. Vaginal and endocervical samples, usually taken during the first trimester of pregnancy were delayed and taken during the last trimester of pregnancy. A macroscopic examination described the aspect of the vagina, the cervix uteri, leukorrhea and of possible inflammatory lesions or ulcerations. A microscopic examination searched for parasites, epithelial cells, clue cells and leukocytes. The appropriate bacteriological cultures were performed after reading the Gram stain and scoring the vaginal flora. The clinical and cytobacteriological aspects were used to identify the bacterial ecology and the pathological genital states. An exploration was carried out in every newborn suspected of infection. Genital samples were collected from 306 pregnant women. Among them, 118 were at 29-32 weeks of gestation, 104 at 33-36, and 84 at 37-40. The most frequent germs were C. albicans (33,5%), Enterbacteriaceae (20.3%) including E. coli (10.9%), S. aureus (15.4%), Gardnerella (13.6%), and Trichomonas (10.6%), in monomicrobian (79.2%) and polymicrobian carriage (20.8%). Lower genital tract pathological states such as vaginitis (29.4%), bacterial vaginosis (21.5%) or endocervicitis (10.4%), asymptomatic bacterial carriage (23.5%) and normal genital flora (15%) were identified. These pregnancies led to 334 live births with 27 cases of early-onset neonatal sepsis to which endocervicitis (25%) and vaginosis (19,7%) were most often linked. Genital samples at the last trimester of pregnancy could evaluate the risk of maternofoetal infections and allow to adapt a drug prophylaxis of Enterobacteriaceae, the most frequent germ of

  1. Early-onset dropped head syndrome after radiotherapy for head and neck cancer: dose constraints for neck extensor muscles

    International Nuclear Information System (INIS)

    Inaba, Koji; Nakamura, Satoshi; Okamoto, Hiroyuki; Kashihara, Tairo; Kobayashi, Kazuma; Harada, Ken; Kitaguchi, Mayuka; Sekii, Shuhei; Takahashi, Kana; Murakami, Naoya; Ito, Yoshinori; Igaki, Hiroshi; Uno, Takashi; Itami, Jun

    2016-01-01

    Dropped head syndrome (DHS) is a famous but unusual late complication of multimodality treatment for head and neck carcinoma. We reported this early-onset complication and analyzed the dose to the neck extensor muscles. We examined the records of three patients with DHS after radiotherapy. The doses to the neck extensor muscles were compared between three patients with DHS and nine patients without DHS. The mean dose to the neck extensor muscles of the three patients with DHS were 58.5 Gy, 42.3 Gy and 60.9 Gy, while the dose was <50 Gy in all nine patients in the control group. The onset of this syndrome was 5 months, 6 months and 15 months. The early-onset DHS may have something to do with dose to the neck extensor muscles. The proposed dose to the neck extensor muscles might be <46 Gy (or at least <50 Gy)

  2. Epidural Brain Metastases in a Patient with Early Onset Pancreatic Cancer: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Aibek E. Mirrakhimov

    2012-01-01

    Full Text Available We present a case of early onset pancreatic cancer related extra-axial brain metastases. A 46-year-old Caucasian non-Jewish nonobese male with a history of PC diagnosed 3 months ago with metastases to the liver, omentum, malignant ascites, and a history of a pulmonary embolism was admitted to the hospital because of a new onset headache, nausea, and vomiting which started 2 days prior to the encounter. Brain MRI was ordered, which showed acute bihemispheric subdural hematomas and left hemispheric extra-axial heterogeneously enhancing lesions consisting with metastatic disease. The patient was started on ondansentron, metoclopramide, and dexamethasone. The cranial irradiation was started, and the patient’s headache and nausea significantly improved. There are only 9 published reports of extra-axial brain metastases related to the pancreatic cancer, whereas our paper is the first such case reported on a patient with epidural metastases and early onset pancreatic cancer.

  3. OS090. Performance of candidate clinical and biochemical markers in screening early in pregnancy to detect women at high risk to develop preeclampsia.

    Science.gov (United States)

    Forest, J-C; Massé, J; Bujold, E; Rousseau, F; Charland, M; Thériault, S; Lafond, J; Giguère, Y

    2012-07-01

    The advent of early preventive measures, such as low-dose aspirin targeting women at high risk of preeclampsia (PE), emphasizes the need for better detection. Despite the emergence of promising biochemical markers linked to the pathophysiological processes, systematic reviews have shown that, until now, no single tests fulfill the criteria set by WHO for biomarkers to screen for a disease. However, recent literature reveals that by combining various clinical, biophysical and biochemical markers into multivariate algorithms, one can envisage to estimate the risk of PE with a performance that would reach clinical utility and cost-effectiveness, but this remains to be demonstrated in various environments and health care settings. To investigate, in a prospective study, the clinical utility of candidate biomarkers and clinical data to detect, early in pregnancy, women at risk to develop PE and to propose a multivariate prediction algorithm combining clinical parameters to biochemical markers. 7929 pregnant women prospectively recruited at the first prenatal visit, provided blood samples, clinical and sociodemographic information. 214 pregnant women developed hypertensive disorders of pregnancy (HDP) of which 88 had PE (1.2%), including 44 with severe PE (0.6%). A nested case-control study was performed including for each case of HDP two normal pregnancies matched for maternal age, gestational age at recruitment, ethnicity, parity, and smoking status. Based on the literature we selected the most promising markers in a multivariate logistic regression model: mean arterial pressure (MAP), BMI, placental growth factor (PlGF), soluble Flt-1, inhibin A and PAPP-A. Biomarker results measured between 10-18 weeks gestation were expressed as multiples of the median. Medians were determined for each gestational week. When combined with MAP at the time of blood sampling and BMI at the beginning of pregnancy, the four biochemical markers discriminate normal pregnancies from those

  4. Combined effect of TLR2 gene polymorphism and early life stress on the age at onset of bipolar disorders.

    Directory of Open Access Journals (Sweden)

    José Oliveira

    Full Text Available Gene-environment interactions may play an important role in modulating the impact of early-life stressful events on the clinical course of bipolar disorder (BD, particularly associated to early age at onset. Immune dysfunction is thought to be an important mechanism linking childhood trauma with early-onset BD, thus the genetic diversity of immune-related loci may account for an important part of the interindividual susceptibility to this severe subform. Here we investigated the potential interaction between genetic variants of Toll-like receptors 2 (TLR2 and 4 (TLR4, major innate immune response molecules to pathogens, and the childhood trauma questionnaire (CTQ in age at onset of BD. We recruited 531 BD patients (type I and II or not otherwise specified, genotyped for the TLR2 rs4696480 and rs3804099 and TLR4 rs1927914 and rs11536891 single-nucleotide polymorphisms and recorded for history of childhood trauma using the CTQ. TLR2 and TLR4 risk genotype carrier state and history of childhood emotional, physical and sexual abuses were evaluated in relation to age at onset as defined by the age at first manic or depressive episode. We observed a combined effect of TLR2 rs3804099 TT genotype and reported sexual abuse on determining an earlier age at onset of BD by means of a Kaplan-Meier survival curve (p = 0.002; corrected p = 0.02. Regression analysis, however, was non-significant for the TLR2-CTQ sexual abuse interaction term. The negative effects of childhood sexual abuse on age at onset of BD may be amplified in TLR2 rs3804099 risk genotype carriers through immune-mediated pathways. Clinical characteristics of illness severity, immune phenotypes and history of early life infectious insults should be included in future studies involving large patient cohorts.

  5. Double-Blind Maintenance Safety and Effectiveness Findings from the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) Study

    Science.gov (United States)

    Findling, Robert L.; Johnson, Jacqueline L.; McClellan, Jon; Frazier, Jean A.; Vitiello, Benedetto; Hamer, Robert M.; Lieberman, Jeffrey A.; Ritz, Louise; McNamara, Nora K.; Lingler, Jacqui; Hlastala, Stefanie; Pierson, Leslie; Puglia, Madeline; Maloney, Ann E.; Kaufman, Emily Michael; Noyes, Nancy; Sikich, Linmarie

    2010-01-01

    Objective: To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders. Method: Patients (8 to 19 years old) who had improved during an 8-week, randomized, double-blind acute trial of olanzapine, risperidone, or molindone (plus benztropine) were eligible to continue on the same medication…

  6. A Meta-Analysis of Neuropsychological Functioning in Patients with Early Onset Schizophrenia and Pediatric Bipolar Disorder

    Science.gov (United States)

    Nieto, Rebeca Garcia; Castellanos, F. Xavier

    2011-01-01

    Despite the nosological distinction between bipolar disorder and schizophrenia, there is increasing evidence that these conditions share phenomenological characteristics. To examine the similarities in their patterns of cognitive impairment, we conducted a meta-analysis from 12 studies of Early Onset Schizophrenia (EOS) and 12 studies of Pediatric…

  7. Comparative study of clinical and neuropsychological characteristics between early-, late and very-late-onset schizophrenia-spectrum disorders.

    Science.gov (United States)

    Hanssen, Manon; van der Werf, Margriet; Verkaaik, Mike; Arts, Baer; Myin-Germeys, Inez; van Os, Jim; Verhey, Frans; Köhler, Sebastian

    2015-08-01

    To compare the clinical and neurocognitive profile of early-onset (EOP, neuropsychological tests from EOP and LOP when age is controlled for. This questions the idea that VLOP is the expression of underlying neurodegeneration. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  8. Thyroid peroxidase antibodies during early gestation and the subsequent risk of first onset postpartum depression : A prospective cohort study

    NARCIS (Netherlands)

    Wesseloo, R.; Kamperman, A.; Bergink, V.; Pop, V.J.M.

    2018-01-01

    Background During the postpartum period, women are at risk for the new onset of both auto-immune thyroid disorders and depression. The presence of thyroid peroxidase antibodies (TPO-ab) during early gestation is predictive for postpartum auto-immune thyroid dysfunction. The aim of this study was to

  9. Impaired Facial Expression Recognition in Children with Temporal Lobe Epilepsy: Impact of Early Seizure Onset on Fear Recognition

    Science.gov (United States)

    Golouboff, Nathalie; Fiori, Nicole; Delalande, Olivier; Fohlen, Martine; Dellatolas, Georges; Jambaque, Isabelle

    2008-01-01

    The amygdala has been implicated in the recognition of facial emotions, especially fearful expressions, in adults with early-onset right temporal lobe epilepsy (TLE). The present study investigates the recognition of facial emotions in children and adolescents, 8-16 years old, with epilepsy. Twenty-nine subjects had TLE (13 right, 16 left) and…

  10. Xp22.3 genomic deletions involving the CDKL5 gene in girls with early onset epileptic encephalopathy.

    Science.gov (United States)

    Mei, Davide; Marini, Carla; Novara, Francesca; Bernardina, Bernardo D; Granata, Tiziana; Fontana, Elena; Parrini, Elena; Ferrari, Anna R; Murgia, Alessandra; Zuffardi, Orsetta; Guerrini, Renzo

    2010-04-01

    Mutations of the X-linked gene cyclin-dependent kinase-like 5 (CDKL5) cause an X-linked encephalopathy with early onset intractable epilepsy, including infantile spasms and other seizure types, and a Rett syndrome (RTT)-like phenotype. Very limited information is available on the frequency and phenotypic spectrum associated with CDKL5 deletions/duplications. We investigated the role of CDKL5 deletions/duplications in causing early onset intractable epilepsy of unknown etiology in girls. We studied 49 girls with early onset intractable epilepsy, with or without infantile spasms, and developmental impairment, for whom no etiologic factors were obvious after clinical examination, brain magnetic resonance imaging (MRI) and expanded screening for inborn errors of metabolism. We performed CDKL5 gene mutation analysis in all and multiplex ligation dependent probe amplification assay (MLPA) in those who were mutation negative. Custom Array-comparative genomic hybridization (CGH), breakpoint polymerase chain reaction (PCR) analysis, and X-inactivation studies were performed in patients in whom MLPA uncovered a genomic alteration. We found CDKL5 mutations in 8.2% (4 of 49) of patients and genomic deletions in 8.2% (4 of 49). Overall, abnormalities of the CDKL5 gene accounted for 16.3% (8 of 49) of patients. CDKL5 gene deletions are an under-ascertained cause of early onset intractable epilepsy in girls. Genetic testing of CDKL5, including both mutation and deletion/duplication analysis, should be considered in this clinical subgroup.

  11. Thyroid peroxidase antibodies during early gestation and the subsequent risk of first-onset postpartum depression: A prospective cohort study

    NARCIS (Netherlands)

    R. Wesseloo (Richard); A.M. Kamperman (Astrid); V. Bergink (Veerle); V.J.M. Pop (Victor)

    2017-01-01

    markdownabstract__Background__ During the postpartum period, women are at risk for the new onset of both auto-immune thyroid disorders and depression. The presence of thyroid peroxidase antibodies (TPO-ab) during early gestation is predictive for postpartum auto-immune thyroid dysfunction. The aim

  12. Precision-cut liver slices as a model for the early onset of liver fibrosis to test antifibrotic drugs

    NARCIS (Netherlands)

    Westra, Inge M.; Oosterhuis, Dorenda; Groothuis, Geny M. M.; Olinga, Peter

    2014-01-01

    Induction of fibrosis during prolonged culture of precision-cut liver slices (PCLS) was reported. In this study, the use of rat PCLS was investigated to further characterize the mechanism of early onset of fibrosis in this model and the effects of antifibrotic compounds. Rat PCLS were incubated for

  13. Is early-onset microsatellite and chromosomally stable colorectal cancer a hallmark of a genetic susceptibility syndrome?

    Science.gov (United States)

    Kets, C M; van Krieken, J H J M; van Erp, P E J; Feuth, T; Jacobs, Y H A; Brunner, H G; Ligtenberg, M J L; Hoogerbrugge, N

    2008-02-15

    Most colorectal cancers show either microsatellite or chromosomal instability. A subset of colorectal cancers, especially those diagnosed at young age, is known to show neither of these forms of genetic instability and thus might have a distinct pathogenesis. Colorectal cancers diagnosed at young age are suggestive for hereditary predisposition. We investigate whether such early-onset microsatellite and chromosomally stable colorectal cancers are a hallmark of a genetic susceptibility syndrome. The ploidy status of microsatellite stable (familial) colorectal cancers of patients diagnosed before age 50 (n = 127) was analyzed in relation to the histopathological characteristics and family history. As a control the ploidy status of sporadic colorectal cancer, with normal staining of mismatch repair proteins, diagnosed at the age of 69 years or above (n = 70) was determined. A diploid DNA content was used as a marker for chromosomal stability. Within the group of patients with (familial) early onset microsatellite stable colorectal cancer the chromosomally stable tumors did not differ from chromosomally unstable tumors with respect to mean age at diagnosis, fulfillment of Amsterdam criteria or pathological characteristics. Segregation analysis did not reveal any family with microsatellite and chromosomally stable colorectal cancer in 2 relatives. The prevalence of microsatellite and chromosomally stable colorectal cancer was not significantly different for the early and late onset group (28 and 21%, respectively). We find no evidence that early-onset microsatellite and chromosomally stable colorectal cancer is a hallmark of a hereditary colorectal cancer syndrome. (c) 2007 Wiley-Liss, Inc.

  14. Slow identification of facial happiness in early adolescence predicts onset of depression during 8 years of follow-up

    NARCIS (Netherlands)

    Vrijen, Charlotte; Hartman, Catharina A.; Oldehinkel, Albertine J.

    Adolescent onset depression places a high burden on those who suffer from it, and is difficult to treat. An improved understanding of mechanisms underlying susceptibility to adolescent depression may be useful in early detection and as target in treatment. Facial emotion identification bias has been

  15. 7T T-2*-weighted magnetic resonance imaging reveals cortical phase differences between early- and late-onset Alzheimer's disease

    NARCIS (Netherlands)

    van Rooden, S.; Doan, N.T.; Versluis, M.J.; Goos, J.D.C.; Webb, A.G.; Oleksik, A.M.; van der Flier, W.M.; Scheltens, P.; Barkhof, F.; Weverlinge-Rynsburger, A.W.E.; Blauw, G. J.; Reiber, J.H.C.; van Buchem, M.A.; Milles, J.; van der Grond, J.

    2015-01-01

    The aim of this study is to explore regional iron-related differences in the cerebral cortex, indicative of Alzheimer's disease pathology, between early- and late-onset Alzheimer's disease (EOAD, LOAD, respectively) patients using 7T magnetic resonance phase images. High-resolution T

  16. Early-Onset Severe Encephalopathy with Epilepsy: The BRAT1 Gene Should Be Added to the List of Causes

    NARCIS (Netherlands)

    van de Pol, L.A.; Wolf, N.I.; van Weissenbruch, M.M.; Stam, C.J.; Weiss, M.M.; Waisfisz, Q.; Kevelam, S.H.; Bugiani, M.; van de Kamp, J.M.; Knaap, M.

    2015-01-01

    A variety of pathologies can underlie early-onset severe encephalopathy with epilepsy. To aid the diagnostic process in such patients we present an overview of causes, including the rapidly expanding list of genes involved. When no explanation is found, whole-exome sequencing (WES) can be used in an

  17. Gain-of-function mutations in potassium channel subunit KCNE2 associated with early-onset lone atrial fibrillation

    DEFF Research Database (Denmark)

    Nielsen, Jonas Bille; Bentzen, Bo Hjorth; Olesen, Morten Salling

    2014-01-01

    Aims: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Disturbances in cardiac potassium conductance are considered as one of the disease mechanisms in AF. We aimed to investigate if mutations in potassium-channel β-subunits KCNE2 and KCNE3 are associated with early-onset lone AF. ...

  18. Association of Early-Onset Spasticity and Risk for Cognitive Impairment With Mutations at Amino Acid 499 in SPAST.

    Science.gov (United States)

    Gillespie, Meredith K; Humphreys, Peter; McMillan, Hugh J; Boycott, Kym M

    2018-04-01

    Hereditary spastic paraplegia is a phenotypically and genetically heterogeneous group of neurodegenerative disorders characterized by lower extremity weakness and spasticity. Spastic paraplegia 4 (SPG4), caused by heterozygous mutations in the gene SPAST, typically causes a late-onset, uncomplicated form of hereditary spastic paraplegia in affected individuals. Additional clinical features in SPG4 have been reported on occasion, but no genotype-phenotype correlation has been established. Through targeted clinical testing, we identified 2 unrelated female patients with the same de novo p.Arg499His mutation in SPAST. Both patients presented with early-onset spasticity resulting in delayed motor milestones, which led to a diagnosis of cerebral palsy in one child and tethered cord in the other. Review of the literature identified several patients with mutations at amino acid 499 and early-onset symptoms associated with a risk of cognitive impairment. Early and accurate diagnosis of children with early-onset spasticity is important for informed prognosis and genetic counselling.

  19. Th1 and Th2 cytokine profile in patiens with early onset periodontitis and their healthy siblings

    Czech Academy of Sciences Publication Activity Database

    Bártová, J.; Krátka-Opatrná, Z.; Procházková, J.; Krejsa, O.; Dušková, J.; Mrklas, L.; Tlaskalová, Helena; Cukrowska, Božena

    2000-01-01

    Roč. 9, - (2000), s. 115-120 ISSN 0962-9351 R&D Projects: GA MZd NK5006 Institutional research plan: CEZ:AV0Z5020903 Keywords : early onset periodontitis * immunoglobulin Subject RIV: EC - Immunology Impact factor: 0.990, year: 2000

  20. Assessing the Clinical Role of Genetic Markers of Early-Onset Prostate Cancer Among High-Risk Men Enrolled in Prostate Cancer Early Detection

    Science.gov (United States)

    Hughes, Lucinda; Zhu, Fang; Ross, Eric; Gross, Laura; Uzzo, Robert G.; Chen, David Y. T.; Viterbo, Rosalia; Rebbeck, Timothy R.; Giri, Veda N.

    2011-01-01

    Background Men with familial prostate cancer (PCA) and African American men are at risk for developing PCA at younger ages. Genetic markers predicting early-onset PCA may provide clinically useful information to guide screening strategies for high-risk men. We evaluated clinical information from six polymorphisms associated with early-onset PCA in a longitudinal cohort of high-risk men enrolled in PCA early detection with significant African American participation. Methods Eligibility criteria include ages 35–69 with a family history of PCA or African American race. Participants undergo screening and biopsy per study criteria. Six markers associated with early-onset PCA (rs2171492 (7q32), rs6983561 (8q24), rs10993994 (10q11), rs4430796 (17q12), rs1799950 (17q21), and rs266849 (19q13)) were genotyped. Cox models were used to evaluate time to PCA diagnosis and PSA prediction for PCA by genotype. Harrell’s concordance index was used to evaluate predictive accuracy for PCA by PSA and genetic markers. Results 460 participants with complete data and ≥1 follow-up visit were included. 56% were African American. Among African American men, rs6983561 genotype was significantly associated with earlier time to PCA diagnosis (p=0.005) and influenced prediction for PCA by the PSA (p<0.001). When combined with PSA, rs6983561 improved predictive accuracy for PCA compared to PSA alone among African American men (PSA= 0.57 vs. PSA+rs6983561=0.75, p=0.03). Conclusions Early-onset marker rs6983561 adds potentially useful clinical information for African American men undergoing PCA risk assessment. Further study is warranted to validate these findings. Impact Genetic markers of early-onset PCA have potential to refine and personalize PCA early detection for high-risk men. PMID:22144497

  1. Early Subchondral Bone Loss at Arthritis Onset Predicted Late Arthritis Severity in a Rat Arthritis Model.

    Science.gov (United States)

    Courbon, Guillaume; Cleret, Damien; Linossier, Marie-Thérèse; Vico, Laurence; Marotte, Hubert

    2017-06-01

    Synovitis is usually observed before loss of articular function in rheumatoid arthritis (RA). In addition to the synovium and according to the "Inside-Outside" theory, bone compartment is also involved in RA pathogenesis. Then, we investigated time dependent articular bone loss and prediction of early bone loss to late arthritis severity on the rat adjuvant-induced arthritis (AIA) model. Lewis female rats were longitudinally monitored from arthritis induction (day 0), with early (day 10) and late (day 17) steps. Trabecular and cortical microarchitecture parameters of four ankle bones were assessed by microcomputed tomography. Gene expression was determined at sacrifice. Arthritis occurred at day 10 in AIA rats. At this time, bone erosions were detected on four ankle bones, with cortical porosity increase (+67%) and trabecular alterations including bone volume fraction (BV/TV: -13%), and trabecular thickness decrease. Navicular bone assessment was the most reproducible and sensitive. Furthermore, strong correlations were observed between bone alterations at day 10 and arthritis severity or bone loss at day 17, including predictability of day 10 BV/TV to day 17 articular index (R 2  = 0.76). Finally, gene expression at day 17 confirmed massive osteoclast activation and interestingly provided insights on strong activation of bone formation inhibitor markers at the joint level. In rat AIA, bone loss was already observed at synovitis onset and was predicted late arthritis severity. Our results reinforced the key role of subchondral bone in arthritis pathogenesis, in favour to the "Inside-Outside" theory. Mechanisms of bone loss in rat AIA involved resorption activation and formation inhibition changes. J. Cell. Physiol. 232: 1318-1325, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Early-onset, severe, and recurrent primary hyperparathyroidism associated with a novel CDC73 mutation.

    Science.gov (United States)

    Shibata, Yusuke; Yamazaki, Masanori; Takei, Masahiro; Uchino, Shinya; Sakurai, Akihiro; Komatsu, Mitsuhisa

    2015-01-01

    Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare autosomal dominant hereditary tumor syndrome characterized by synchronous or metachronous occurrence of primary hyperparathyroidism (PHPT), ossifying fibroma of the maxilla and/or mandible, renal tumor and uterine tumors. Early diagnosis of this syndrome is essential because it is associated with increased risk of parathyroid cancer. A 30-year-old man with urolithiasis had severe hypercalcemia (15.0 mg/dL after correction) induced by inappropriate parathyroid hormone (PTH) secretion (intact PTH 1390 pg/mL), indicating severe PHPT. An underlying parathyroid tumor was surgically removed and was histologically confirmed to be an adenoma. However, PHPT due to another parathyroid tumor reoccurred two years after the surgery. Although no HPT-JT-associated manifestations other than PHPT were detected, HPT-JT was strongly suspected based on the exclusion of multiple endocrine neoplasia (MEN) and the young age of disease occurrence. Genetic analysis revealed a novel nonsense mutation (p.Arg91X; c.271C>T) in exon 3 of the causative gene, CDC73, which encodes the tumor suppressor protein parafibromin. The residual parathyroid glands were all removed without autotransplantation of parathyroid gland taking into consideration prospective parathyroid carcinogenesis. The resected parathyroid tumor was also an adenoma. The present case highlights that HPT-JT should be considered and CDC73 mutation analysis should be performed, especially in cases of early-onset PHPT, recurrent PHPT, PHPT with polyglandular parathyroid involvement, and PHPT presenting with severe hypercalcemia even if there is no positive family history.

  3. Impaired Verbal Learning Is Associated with Larger Caudate Volumes in Early Onset Schizophrenia Spectrum Disorders.

    Directory of Open Access Journals (Sweden)

    Monica Juuhl-Langseth

    Full Text Available Both brain structural abnormalities and neurocognitive impairments are core features of schizophrenia. We have previously reported enlargements in subcortical brain structure volumes and impairment of neurocognitive functioning as measured by the MATRICS Cognitive Consensus Battery (MCCB in early onset schizophrenia spectrum disorders (EOS. To our knowledge, no previous study has investigated whether neurocognitive performance and volumetric abnormalities in subcortical brain structures are related in EOS.Twenty-four patients with EOS and 33 healthy controls (HC were included in the study. Relationships between the caudate nucleus, the lateral and fourth ventricles volumes and neurocognitive performance were investigated with multivariate linear regression analyses. Intracranial volume, age, antipsychotic medication and IQ were included as independent predictor-variables.The caudate volume was negatively correlated with verbal learning performance uniquely in the EOS group (r=-.454, p=.034. There were comparable positive correlations between the lateral ventricular volume and the processing speed, attention and reasoning and problem solving domains for both the EOS patients and the healthy controls. Antipsychotic medication was related to ventricular enlargements, but did not affect the brain structure-function relationship.Enlargement of the caudate volume was related to poorer verbal learning performance in patients with EOS. Despite a 32% enlargement of the lateral ventricles in the EOS group, associations to processing speed, attention and reasoning and problem solving were similar for both the EOS and the HC groups.

  4. Early Onset Intrauterine Growth Restriction in a Mouse Model of Gestational Hypercholesterolemia and Atherosclerosis

    Science.gov (United States)

    Busso, Dolores; Mascareño, Lilian; Salas, Francisca; Berkowitz, Loni; Santander, Nicolás; Quiroz, Alonso; Amigo, Ludwig; Valdés, Gloria; Rigotti, Attilio

    2014-01-01

    The susceptibility to develop atherosclerosis is increased by intrauterine growth restriction and prenatal exposure to maternal hypercholesterolemia. Here, we studied whether mouse gestational hypercholesterolemia and atherosclerosis affected fetal development and growth at different stages of gestation. Female LDLR KO mice fed a proatherogenic, high cholesterol (HC) diet for 3 weeks before conception and during pregnancy exhibited a significant increase in non-HDL cholesterol and developed atherosclerosis. At embryonic days 12.5 (E12.5), E15.5, and E18.5, maternal gestational hypercholesterolemia and atherosclerosis were associated to a 22–24% reduction in male and female fetal weight without alterations in fetal number/litter or morphology nor placental weight or structure. Feeding the HC diet exclusively at the periconceptional period did not alter fetal growth, suggesting that maternal hypercholesterolemia affected fetal weight only after implantation. Vitamin E supplementation (1,000 UI of α-tocopherol/kg) of HC-fed females did not change the mean weight of E18.5 fetuses but reduced the percentage of fetuses exhibiting body weights below the 10th percentile of weight (HC: 90% vs. HC/VitE: 68%). In conclusion, our results showed that maternal gestational hypercholesterolemia and atherosclerosis in mice were associated to early onset fetal growth restriction and that dietary vitamin E supplementation had a beneficial impact on this condition. PMID:25295255

  5. Early-onset invasive aspergillosis and other fungal infections in patients treated with ibrutinib.

    Science.gov (United States)

    Ghez, David; Calleja, Anne; Protin, Caroline; Baron, Marine; Ledoux, Marie-Pierre; Damaj, Gandhi; Dupont, Mathieu; Dreyfus, Brigitte; Ferrant, Emmanuelle; Herbaux, Charles; Laribi, Kamel; Le Calloch, Ronan; Malphettes, Marion; Paul, Franciane; Souchet, Laetitia; Truchan-Graczyk, Malgorzata; Delavigne, Karen; Dartigeas, Caroline; Ysebaert, Loïc

    2018-04-26

    Ibrutinib has revolutionized the management of chronic lymphocytic leukemia and is now being increasingly used. Although considered to be less immunosuppressive than conventional immunochemotherapy, the observation of a few cases of invasive fungal infections in patients treated with ibrutinib prompted us to conduct a retrospective survey. We identified 33 cases of invasive fungal infections in patients receiving ibrutinib alone or in combination. Invasive aspergillosis (IA) was overrepresented (27/33) and was associated with cerebral localizations in 40% of the cases. Remarkably, most cases of invasive fungal infections occurred with a median of 3 months after starting ibrutinib. In 18/33 cases, other conditions that could have contributed to decreased antifungal responses, such as corticosteroids, neutropenia, or combined immunochemotherapy, were present. These observations indicate that ibrutinib may be associated with early-onset invasive fungal infections, in particular IA with frequent cerebral involvement, and that patients on ibrutinib should be closely monitored in particular when other risk factors of fungal infections are present. © 2018 by The American Society of Hematology.

  6. Copper to Zinc Ratio as Disease Biomarker in Neonates with Early-Onset Congenital Infections

    Science.gov (United States)

    Wisniewska, Monika; Cremer, Malte; Wiehe, Lennart; Becker, Niels-Peter; Rijntjes, Eddy; Martitz, Janine; Renko, Kostja; Bührer, Christoph; Schomburg, Lutz

    2017-01-01

    Copper (Cu) and zinc (Zn) are essential trace elements for regular development. Acute infections alter their metabolism, while deficiencies increase infection risks. A prospective observational case-control study was conducted with infected (n = 21) and control (n = 23) term and preterm newborns. We analyzed trace element concentrations by X-ray fluorescence, and ceruloplasmin (CP) by Western blot. Median concentration of Cu at birth (day 1) was 522.8 [387.1–679.7] μg/L, and Zn was 1642.4 ± 438.1 μg/L. Cu and Zn correlated positively with gestational age in control newborns. Cu increased in infected newborns from day 1 to day 3. CP correlated positively to Cu levels at birth in both groups and on day 3 in the group of infected neonates. The Cu/Zn ratio was relatively high in infected newborns. Interleukin (IL)-6 concentrations on day 1 were unrelated to Cu, Zn, or the Cu/Zn ratio, whereas C-reactive protein (CRP) levels on day 3 correlated positively to the Cu/Zn -ratio at both day 1 and day 3. We conclude that infections affect the trace element homeostasis in newborns: serum Zn is reduced, while Cu and CP are increased. The Cu/Zn ratio combines both alterations, independent of gestational age. It may, thus, constitute a meaningful diagnostic biomarker for early-onset infections. PMID:28358335

  7. Women's accounts of help-seeking in early rheumatoid arthritis from symptom onset to diagnosis.

    Science.gov (United States)

    Townsend, Anne; Backman, Catherine L; Adam, Paul; Li, Linda C

    2014-12-01

    As interest in gender and health grows, the notion that women are more likely than men to consult doctors is increasingly undermined as more complex understandings of help seeking and gender emerge. While men's reluctance to seek help is associated with practices of masculinities, there has been less consideration of women's help-seeking practices. Rheumatoid arthritis (RA) is a chronic disease that predominantly affects women and requires prompt treatment but considerable patient-based delays persist along the care pathway. This paper examines women's accounts of help seeking in early RA from symptom onset to diagnosis. We conducted in-depth interviews with 37 women with RA masculine practices associated with men's help-seeking. The women presented such behaviours as relational, e.g. rooted in family socialisation and a determination to maintain roles and 'normal' life. Our findings raise questions about how far notions of gender operate to differentiate men and women's help seeking and may indicate more similarities than differences. Recognising this has implications for policy and practice initiatives for both men and women. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  8. High frequency of potentially pathogenic SORL1 mutations in autosomal dominant early-onset Alzheimer disease.

    Science.gov (United States)

    Pottier, C; Hannequin, D; Coutant, S; Rovelet-Lecrux, A; Wallon, D; Rousseau, S; Legallic, S; Paquet, C; Bombois, S; Pariente, J; Thomas-Anterion, C; Michon, A; Croisile, B; Etcharry-Bouyx, F; Berr, C; Dartigues, J-F; Amouyel, P; Dauchel, H; Boutoleau-Bretonnière, C; Thauvin, C; Frebourg, T; Lambert, J-C; Campion, D

    2012-09-01

    Performing exome sequencing in 14 autosomal dominant early-onset Alzheimer disease (ADEOAD) index cases without mutation on known genes (amyloid precursor protein (APP), presenilin1 (PSEN1) and presenilin2 (PSEN2)), we found that in five patients, the SORL1 gene harbored unknown nonsense (n=1) or missense (n=4) mutations. These mutations were not retrieved in 1500 controls of same ethnic origin. In a replication sample, including 15 ADEOAD cases, 2 unknown non-synonymous mutations (1 missense, 1 nonsense) were retrieved, thus yielding to a total of 7/29 unknown mutations in the combined sample. Using in silico predictions, we conclude that these seven private mutations are likely to have a pathogenic effect. SORL1 encodes the Sortilin-related receptor LR11/SorLA, a protein involved in the control of amyloid beta peptide production. Our results suggest that besides the involvement of the APP and PSEN genes, further genetic heterogeneity, involving another gene of the same pathway is present in ADEOAD.

  9. SORL1 rare variants: a major risk factor for familial early-onset Alzheimer's disease.

    Science.gov (United States)

    Nicolas, G; Charbonnier, C; Wallon, D; Quenez, O; Bellenguez, C; Grenier-Boley, B; Rousseau, S; Richard, A-C; Rovelet-Lecrux, A; Le Guennec, K; Bacq, D; Garnier, J-G; Olaso, R; Boland, A; Meyer, V; Deleuze, J-F; Amouyel, P; Munter, H M; Bourque, G; Lathrop, M; Frebourg, T; Redon, R; Letenneur, L; Dartigues, J-F; Génin, E; Lambert, J-C; Hannequin, D; Campion, D

    2016-06-01

    The SORL1 protein plays a protective role against the secretion of the amyloid β peptide, a key event in the pathogeny of Alzheimer's disease. We assessed the impact of SORL1 rare variants in early-onset Alzheimer's disease (EOAD) in a case-control setting. We conducted a whole exome analysis among 484 French EOAD patients and 498 ethnically matched controls. After collapsing rare variants (minor allele frequency ≤1%), we detected an enrichment of disruptive and predicted damaging missense SORL1 variants in cases (odds radio (OR)=5.03, 95% confidence interval (CI)=(2.02-14.99), P=7.49.10(-5)). This enrichment was even stronger when restricting the analysis to the 205 cases with a positive family history (OR=8.86, 95% CI=(3.35-27.31), P=3.82.10(-7)). We conclude that predicted damaging rare SORL1 variants are a strong risk factor for EOAD and that the association signal is mainly driven by cases with positive family history.

  10. Cross-sex pattern of bone mineral density in early onset gender identity disorder.

    Science.gov (United States)

    Haraldsen, I R; Haug, E; Falch, J; Egeland, T; Opjordsmoen, S

    2007-09-01

    Hormonally controlled differences in bone mineral density (BMD) between males and females are well studied. The effects of cross-sex hormones on bone metabolism in patients with early onset gender identity disorder (EO-GID), however, are unclear. We examined BMD, total body fat (TBF) and total lean body mass (TLBM) in patients prior to initiation of sex hormone treatment and during treatment at months 3 and 12. The study included 33 EO-GID patients who were approved for sex reassignment and a control group of 122 healthy Norwegians (males, n=77; females, n=45). Male patients (n=12) received an oral dose of 50 mug ethinylestradiol daily for the first 3 months and 100 mug daily thereafter. Female patients (n=21) received 250 mg testosterone enantate intramuscularly every third week. BMD, TBF and TLBM were estimated using dual energy X-ray absorptiometry (DXA). In male patients, the DXA measurements except TBF were significantly lower compared to their same-sex control group at baseline and did not change during treatment. In female patients, the DXA measurements were slightly higher than in same-sex controls at baseline and also remained unchanged during treatment. In conclusion, this study reports that body composition and bone density of EO-GID patients show less pronounced sex differences compared to controls and that bone density was unaffected by cross-sex hormone treatment.

  11. Mutation in an alternative transcript of CDKL5 in a boy with early-onset seizures.

    Science.gov (United States)

    Bodian, Dale L; Schreiber, John M; Vilboux, Thierry; Khromykh, Alina; Hauser, Natalie S

    2018-06-01

    Infantile-onset epilepsies are a set of severe, heterogeneous disorders for which clinical genetic testing yields causative mutations in ∼20%-50% of affected individuals. We report the case of a boy presenting with intractable seizures at 2 wk of age, for whom gene panel testing was unrevealing. Research-based whole-genome sequencing of the proband and four unaffected family members identified a de novo mutation, NM_001323289.1:c.2828_2829delGA in CDKL5, a gene associated with X-linked early infantile epileptic encephalopathy 2. CDKL5 has multiple alternative transcripts, and the mutation lies in an exon in the brain-expressed forms. The mutation was undetected by gene panel sequencing because of its intronic location in the CDKL5 transcript typically used to define the exons of this gene for clinical exon-based tests (NM_003159). This is the first report of a patient with a mutation in an alternative transcript of CDKL5 This finding suggests that incorporating alternative transcripts into the design and variant interpretation of exon-based tests, including gene panel and exome sequencing, could improve the diagnostic yield. © 2018 Bodian et al.; Published by Cold Spring Harbor Laboratory Press.

  12. Factor V leiden and ischemic stroke risk: the Genetics of Early Onset Stroke (GEOS) study.

    Science.gov (United States)

    Hamedani, Ali G; Cole, John W; Cheng, Yuching; Sparks, Mary J; O'Connell, Jeffrey R; Stine, Oscar C; Wozniak, Marcella A; Stern, Barney J; Mitchell, Braxton D; Kittner, Steven J

    2013-05-01

    Factor V Leiden (FVL) has been associated with ischemic stroke in children but not in adults. Although the FVL mutation is associated with increased risk for venous thrombosis, its association with ischemic stroke in young adults remains uncertain. Therefore, we examined the association between FVL and ischemic stroke in participants of the Genetics of Early Onset Stroke (GEOS) study. A population-based case control study identified 354 women and 476 men 15 to 49 years of age with first-ever ischemic stroke and 907 controls. Participant-specific data included vascular risk factors, FVL genotype and, for cases, the ischemic stroke subtype by modified Trial of ORG 10172 in Acute Stroke criteria. Logistic regression was used to calculate odds ratios for the entire population and for subgroups stratified by risk factors and ischemic stroke subtype. The frequency of the FVL mutation was similar between ischemic stroke patients (3.6%; 95% confidence interval [CI] 2.5%-5.1%) and nonstroke controls (3.8%; 95% CI 2.7%-5.2%). This frequency did not change significantly when cases were restricted to patients with stroke of undetermined etiology (4.1%; 95% CI 2.6%-6.4%). Among young adults, we found no evidence for an association between FVL and either all ischemic stroke or the subgroup with stroke of undetermined etiology. Published by Elsevier Inc.

  13. Children's parasympathetic reactivity to specific emotions moderates response to intervention for early-onset aggression.

    Science.gov (United States)

    Gatzke-Kopp, Lisa M; Greenberg, Mark; Bierman, Karen

    2015-01-01

    Following theories that individual differences in respiratory sinus arrhythmia (RSA) denote differential sensitivity to environmental influences, this study examines whether differences in RSA reactivity to specific emotional challenges predict differential response to intervention. We present data from a randomized clinical trial of a targeted intervention for early onset aggression. In collaboration with a high-risk urban school district, 207 kindergarten children (73% African American, 66% male), identified by their teachers as having high levels of aggressive and disruptive behavior, were recruited. All children received a universal social-emotional curriculum. One hundred children were randomly assigned to an additional intervention consisting of weekly peer-based social skills training. Complete RSA data were available for 139 of the children. Teacher-reported externalizing symptoms and emotion regulation in 1st grade (post intervention) were examined controlling for baseline levels. First-grade peer nominations of aggressive behavior, controlling for baseline nominations, were also examined as outcomes. No effect of resting RSA was found. However, greater reactivity to anger was associated with higher externalizing symptoms and lower emotion regulation skills in 1st grade relative to low reactive children. Lower reactivity to fear was associated with greater improvement over time, an effect that was enhanced in the targeted intervention condition. Results suggest that measures of affective reactivity may provide insight into children's capacity to benefit from different types of interventions.

  14. Web survey of sleep problems associated with early-onset bipolar spectrum disorders.

    Science.gov (United States)

    Lofthouse, Nicholas; Fristad, Mary; Splaingard, Mark; Kelleher, Kelly; Hayes, John; Resko, Susan

    2008-05-01

    As research on sleep difficulties associated with Early-Onset Bipolar Spectrum Disorders (EBSD) is limited, a web-based survey was developed to further explore these problems. 494 parents of 4-to-12 year-olds, identified by parents as being diagnosed with EBSD, completed a web survey about past and current EBSD-related sleep problems. The survey included Children's Sleep Habits Questionnaire (CSHQ) items and sleep problems from the International Classification of Sleep Disorders 2nd edition. Nearly all parents reported some type of past or current EBSD-sleep problem. Most occurred during a worst mood period, particularly with mixed manic-depressive symptoms. Symptoms caused impairments at home, school, or with peers in 96.9% of the sample and across all three contexts in 64.0% of children. Sleep problems were also noted after three-day weekends and Spring and Fall Daylight Savings time changes. Findings, study limitations, and implications for treatment and etiology are discussed.

  15. Reduced Cortisol in Boys with Early-Onset Conduct Disorder and Callous-Unemotional Traits

    Directory of Open Access Journals (Sweden)

    Georg G. von Polier

    2013-01-01

    Full Text Available Background. A growing body of evidence suggests an association between altered hypothalamic-pituitary-adrenal axis reactivity and the development of persistent antisocial behavior in children. However the effects of altered cortisol levels remain poorly understood in the complex context of conduct disorder, callous-unemotional (CU personality traits, and frequent comorbidities, such as attention deficit hyperactivity disorder (ADHD. The aim of the current study was to investigate associations among CU traits, antisocial behavior, and comorbid ADHD symptomatology with cortisol levels in male children and adolescents. Methods. The study included 37 boys with early-onset conduct disorder (EO-CD, mean age 11.9 years and 38 healthy boys (mean age 12.5 years. Participants were subjected to multiple daytime salivary cortisol measurements and a psychometric characterization. Results. Subjects in the EO-CD group with elevated CU traits showed a diminished cortisol awakening response compared to healthy participants. In the EO-CD group, high CU traits and impulsivity were associated with decreased diurnal cortisol levels, while associations with antisocial behavior were not detected. The cortisol awakening response was significantly inversely associated with hyperactivity (P=0.02 and marginally significant with CU traits (P=0.07. Conclusions. These results indicate a specific association between CU traits and a diminished stress response, which is not explained by antisocial behavior in general.

  16. Identification of probable early-onset biomarkers for tuberculosis disease progression.

    Directory of Open Access Journals (Sweden)

    Jayne S Sutherland

    Full Text Available Determining what constitutes protective immunity to TB is critical for the development of improved diagnostics and vaccines. The comparison of the immune system between contacts of TB patients, who later develop TB disease (progressors, versus contacts who remain healthy (non-progressors, allows for identification of predictive markers of TB disease. This study provides the first comprehensive analysis of the immune system of progressors and non-progressors using a well-characterised TB case-contact (TBCC platform in The Gambia, West Africa. 22 progressors and 31 non-progressors were analysed at recruitment, 3 months and 18 months (time to progression: median[IQR] of 507[187-714] days. Immunophenotyping of PBMC, plasma cytokine levels and RT-MLPA analysis of whole blood-derived RNA was performed to capture key immune system parameters. At recruitment, progressors had lower PBMC proportions of CD4+ T cells, NKT cells and B cells relative to non-progressors. Analysis of the plasma showed higher levels of IL-18 in progressors compared to non-progressors and analysis of the RNA showed significantly lower gene expression of Bcl2 but higher CCR7 in progressors compared to non-progressors. This study shows several markers that may predict the onset of active TB at a very early stage after infection. Once these markers have been validated in larger studies, they provide avenues to prospectively identify people at risk of developing TB, a key issue in the testing of new TB vaccines.

  17. A high degree of LINE-1 hypomethylation is a unique feature of early-onset colorectal cancer.

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    Marina Antelo

    Full Text Available Early-onset colorectal cancer (CRC represents a clinically distinct form of CRC that is often associated with a poor prognosis. Methylation levels of genomic repeats such as LINE-1 elements have been recognized as independent factors for increased cancer-related mortality. The methylation status of LINE-1 elements in early-onset CRC has not been analyzed previously.We analyzed 343 CRC tissues and 32 normal colonic mucosa samples, including 2 independent cohorts of CRC diagnosed ≤ 50 years old (n=188, a group of sporadic CRC >50 years (MSS n=89; MSI n=46, and a group of Lynch syndrome CRCs (n=20. Tumor mismatch repair protein expression, microsatellite instability status, LINE-1 and MLH1 methylation, somatic BRAF V600E mutation, and germline MUTYH mutations were evaluated.Mean LINE-1 methylation levels (± SD in the five study groups were early-onset CRC, 56.6% (8.6; sporadic MSI, 67.1% (5.5; sporadic MSS, 65.1% (6.3; Lynch syndrome, 66.3% (4.5 and normal mucosa, 76.5% (1.5. Early-onset CRC had significantly lower LINE-1 methylation than any other group (p<0.0001. Compared to patients with <65% LINE-1 methylation in tumors, those with ≥ 65% LINE-1 methylation had significantly better overall survival (p=0.026, log rank test.LINE-1 hypomethylation constitutes a potentially important feature of early-onset CRC, and suggests a distinct molecular subtype. Further studies are needed to assess the potential of LINE-1 methylation status as a prognostic biomarker for young people with CRC.

  18. Vascular dysfunction in preeclampsia.

    Science.gov (United States)

    Brennan, Lesley J; Morton, Jude S; Davidge, Sandra T

    2014-01-01

    Preeclampsia is a complex disorder which affects an estimated 5% of all pregnancies worldwide. It is diagnosed by hypertension in the presence of proteinuria after the 20th week of pregnancy and is a prominent cause of maternal morbidity and mortality. As delivery is currently the only known treatment, preeclampsia is also a leading cause of preterm delivery. Preeclampsia is associated with maternal vascular dysfunction, leading to serious cardiovascular risk both during and following pregnancy. Endothelial dysfunction, resulting in increased peripheral resistance, is an integral part of the maternal syndrome. While the cause of preeclampsia remains unknown, placental ischemia resulting from aberrant placentation is a fundamental characteristic of the disorder. Poor placentation is believed to stimulate the release of a number of factors including pro- and antiangiogenic factors and inflammatory activators into the maternal systemic circulation. These factors are critical mediators of vascular function and impact the endothelium in distinctive ways, including enhanced endothelial oxidative stress. The mechanisms of action and the consequences on the maternal vasculature will be discussed in this review. © 2013 John Wiley & Sons Ltd.

  19. Calciuria and preeclampsia

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    Ramos J.G.L.

    1998-01-01

    Full Text Available Urinary calcium excretion has been reported to be diminished in preeclampsia. The objective of the present study was to determine urinary calcium excretion in pregnant patients with chronic arterial hypertension (CAH and preeclampsia (PE, and in normotensive patients (N. Forty-four pregnant patients (gestional age, 20-42 weeks; 18 CAH, 17 PE, 9 N were evaluated for calciuria, proteinuria, plasma uric acid and blood pressure. Patients with PE (82 ± 15.1 mg/24 h showed significantly lower calciuria (P<0.05 than the group with CAH (147 ± 24.9 mg/24 h and the N group (317 ± 86.0 mg/24 h (P<0.05, Student t-test. Plasma uric acid was significantly higher in the PE group (6.1 ± 0.38 mg/dl than the CAH group (5.0 ± 0.33 mg/dl; P<0.05, which also presented higher proteinuria levels, although the difference was not statistically significant. Diastolic and systolic blood pressure did not differ between the PE (164 ± 105 mmHg and CAH (164 ± 107 mmHg groups. Calciuria was significantly lower in the group with preeclampsia than in the group with chronic arterial hypertension. We conclude that calciuria can be a further factor for identifying preeclampsia

  20. New Insights into the Role of Matrix Metalloproteinases in Preeclampsia.

    Science.gov (United States)

    Espino Y Sosa, Salvador; Flores-Pliego, Arturo; Espejel-Nuñez, Aurora; Medina-Bastidas, Diana; Vadillo-Ortega, Felipe; Zaga-Clavellina, Veronica; Estrada-Gutierrez, Guadalupe

    2017-07-20

    Preeclampsia is a severe pregnancy complication globally, characterized by poor placentation triggering vascular dysfunction. Matrix metalloproteinases (MMPs) exhibit proteolytic activity implicated in the efficiency of trophoblast invasion to the uterine wall, and a dysregulation of these enzymes has been linked to preeclampsia. A decrease in MMP-2 and MMP-9 interferes with the normal remodeling of spiral arteries at early pregnancy stages, leading to the initial pathophysiological changes observed in preeclampsia. Later in pregnancy, an elevation in MMP-2 and MMP-9 induces abnormal release of vasoactive factors conditioning hypertension. Although these two enzymes lead the scene, other MMPs like MMP-1 and MMP-14 seem to have a role in this pathology. This review gathers published recent evidence about the implications of different MMPs in preeclampsia, and the potential use of these enzymes as emergent biomarkers and biological therapeutic targets, focusing on studies involving human subjects.

  1. New Insights into the Role of Matrix Metalloproteinases in Preeclampsia

    Directory of Open Access Journals (Sweden)

    Salvador Espino Y. Sosa

    2017-07-01

    Full Text Available Preeclampsia is a severe pregnancy complication globally, characterized by poor placentation triggering vascular dysfunction. Matrix metalloproteinases (MMPs exhibit proteolytic activity implicated in the efficiency of trophoblast invasion to the uterine wall, and a dysregulation of these enzymes has been linked to preeclampsia. A decrease in MMP-2 and MMP-9 interferes with the normal remodeling of spiral arteries at early pregnancy stages, leading to the initial pathophysiological changes observed in preeclampsia. Later in pregnancy, an elevation in MMP-2 and MMP-9 induces abnormal release of vasoactive factors conditioning hypertension. Although these two enzymes lead the scene, other MMPs like MMP-1 and MMP-14 seem to have a role in this pathology. This review gathers published recent evidence about the implications of different MMPs in preeclampsia, and the potential use of these enzymes as emergent biomarkers and biological therapeutic targets, focusing on studies involving human subjects.

  2. Can early physical therapy positively affect the onset of independent walking in infants with Down syndrome? A retrospective cohort study.

    Science.gov (United States)

    Corrado, Bruno; Sommella, Nadia; Ciardi, Gianluca; Raiano, Enza; Scala, Iris; Strisciuglio, Pietro; Servodio Iammarrone, Clemente

    2018-02-19

    The development of both gross and fine motor skills in a child with Down syndrome is generally delayed. The most seriously affected stage is the achievement of independent walking ability, which influences the onset of all following motor and cognityive skills. The study objectives were (a) to assess the time taken to achieve independent walking ability in a cohort of children with Down syndrome, (b) to examine differences in walking onset by patient characteristics, (c) to verify the effect of early physical therapy (Neurodevelopmental Treatment on the basis of Bobath Concept practised within the first months of life) in the achievement of that skill. A retrospective study was carried out on a cohort of 86 children with Down Syndrome. The knowledge of the exact age of walking onset and information about comorobities and rehabilitation practised since birth were the eligibility criteria. The average age at which walking began in the sample was 26 months (Standard Deviation = 9.66). Some patient characteristics proved to be related negatively to the walking onset: gender male, trisomy 21, improved joint ligamentous laxity. When practised, early physical therapy was able to contrast the delay in walking. NDT-Bobath is a well-known and valid instrument for a child with Down syndrome to attain his highest possible psychomotor functioning level. This study pointed out for the first time ever its capability to contrast the delay on walking onset, which can influences positively the development of the following motor and cognitive skills.

  3. Early Onset of Drug and Polysubstance Use as Predictors of Injection Drug Use Among Adult Drug Users

    Science.gov (United States)

    Trenz, Rebecca C.; Scherer, Michael; Harrell, Paul; Zur, Julia; Sinha, Ashish; Latimer, William

    2012-01-01

    Early onset of alcohol, marijuana, and cigarette use is an indicator of later substance use problems in adulthood such as alcohol or other drug dependence. This paper seeks to address the association between early onset alcohol, marijuana, cigarette, and polysubstance use with injection drug use among recent illicit drug users. The current study used baseline data from the Baltimore site of the NEURO-HIV Epidemiologic Study, an investigation of neuropsychological and social-behavioral risk factors of HIV, hepatitis A, hepatitis B, and Hepatitis C among both injection and non-injection drug users in Baltimore Maryland. The present study used a subset (N = 651) of the larger parent study that identified as White or Black, and reported any drug use in the past 6 months. In the full sample slightly more than half (52.5%) of study participants were IDUs. IDUs differed from non-IDUs on age of initiation for cigarettes, marijuana, and alcohol, with IDUs initiating the use of all three substances significantly earlier than non-IDUs. IDUs also had significantly greater proportions of early onset of alcohol (χ2 = 19.71, p < .01), cigarette (χ2 = 11.05, p < .01), marijuana (χ2 = 10.83, p < .01), and polysubstance use (χ2 = 23.48, p < .01) than non-IDUs. After adjusting for age, gender, and race/ethnicity, only participants identified as early onset alcohol users (AOR = 1.47, 95% CI: 1.00-2.18) and early onset polysubstance users (AOR = 1.62, 95% CI: 1.10-2.38) were more likely to have IDU status than those who reported initiating substance use later. IDU status was then stratified by race/ethnicity. After controlling for age and gender, only early polysubstance use was a significant predictor of IDU status for Whites (AOR = 2.06, 95% CI: 1.07-3.93). Consistent with literature on early substance initiation and later illicit substance use, early onset alcohol and polysubstance use is an important risk factor for IDU in adulthood. PMID:22172686

  4. Minimal alteration in the ratio of circulatory fetal DNA to fetal corticotropin-releasing hormone mRNA level in preeclampsia.

    Science.gov (United States)

    Zhong, Xiao Yan; Holzgreve, Wolfgang; Gebhardt, Stefan; Hillermann, Renate; Tofa, Kashefa Carelse; Gupta, Anurag Kumar; Huppertz, Berthold; Hahn, Sinuhe

    2006-01-01

    We have recently observed that fetal DNA and fetal corticotropin-releasing hormone (CRH) mRNA are associated with in vitro generated syncytiotrophoblast-derived microparticles, and that the ratio of fetal DNA to mRNA (CRH) varied according to whether the particles were derived by predominantly apoptotic, apo-necrotic or necrotic pathways. Hence, we examined whether these ratios varied in maternal plasma samples taken from normotensive and preeclamptic pregnancies in vivo. Maternal plasma samples were collected from 18 cases with preeclampsia and 29 normotensive term controls. Circulatory fetal CRH mRNA and DNA levels were quantified by real-time PCR and RT-PCR. Circulatory fetal mRNA and fetal DNA levels were significantly elevated in the preeclampsia study group when compared to normotensive controls. Alterations in the fetal mRNA to DNA ratio between the study and control groups were minimal, even when stratified into early (34 weeks of gestation) onset preeclampsia. Our data suggest that although circulatory fetal DNA and mRNA levels are significantly elevated in preeclampsia, the ratios in maternal plasma are not dramatically altered. Copyright 2006 S. Karger AG, Basel.

  5. The prevention of early-onset neonatal group B streptococcal disease.

    Science.gov (United States)

    Money, Deborah; Allen, Victoria M

    2013-10-01

    To review the evidence in the literature and to provide recommendations on the management of pregnant women in labour for the prevention of early-onset neonatal group B streptococcal disease. The key revisions in this updated guideline include changed recommendations for regimens for antibiotic prophylaxis, susceptibility testing, and management of women with pre-labour rupture of membranes. Maternal outcomes evaluated included exposure to antibiotics in pregnancy and labour and complications related to antibiotic use. Neonatal outcomes of rates of early-onset group B streptococcal infections are evaluated. Published literature was retrieved through searches of MEDLINE, CINAHL, and The Cochrane Library from January 1980 to July 2012 using appropriate controlled vocabulary and key words (group B streptococcus, antibiotic therapy, infection, prevention). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated in the guideline to May 2013. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). The recommendations in this guideline are designed to help clinicians identify and manage pregnancies at risk for neonatal group B streptococcal disease to optimize maternal and perinatal outcomes. No cost-benefit analysis is provided. There is good evidence based on randomized control trial data that in women with pre-labour rupture of membranes at term who are colonized with group B streptococcus, rates of neonatal infection are

  6. Developing Potential Candidates of Preclinical Preeclampsia

    Directory of Open Access Journals (Sweden)

    Sandra Founds

    2015-11-01

    Full Text Available The potential for developing molecules of interest in preclinical preeclampsia from candidate genes that were discovered on gene expression microarray analysis has been challenged by limited access to additional first trimester trophoblast and decidual tissues. The question of whether these candidates encode secreted proteins that may be detected in maternal circulation early in pregnancy has been investigated using various proteomic methods. Pilot studies utilizing mass spectrometry based proteomic assays, along with enzyme linked immunosorbent assays (ELISAs, and Western immunoblotting in first trimester samples are reported. The novel targeted mass spectrometry methods led to robust multiple reaction monitoring assays. Despite detection of several candidates in early gestation, challenges persist. Future antibody-based studies may lead to a novel multiplex protein panel for screening or detection to prevent or mitigate preeclampsia.

  7. Short communication: Associations between blood glucose concentration, onset of hyperketonemia, and milk production in early lactation dairy cows.

    Science.gov (United States)

    Ruoff, J; Borchardt, S; Heuwieser, W

    2017-07-01

    The objectives of this study were to describe the associations between hypoglycemia and the onset of hyperketonemia (HYK) within the first 6 wk of lactation, to evaluate the effects of body condition score at calving on glucose concentration, and to study the effects of hypoglycemia on milk production. A total of 621 dairy cows from 6 commercial dairy farms in Germany were enrolled between 1 and 4 d in milk (DIM). Cows were tested twice weekly using an electronic handheld meter for glucose and β-hydroxybutyrate (BHB), respectively, for a period of 42 d. Hypoglycemia was defined as glucose concentration ≤2.2 mmol/L. Hyperketonemia was defined as a BHB concentration ≥1.2 mmol/L. The onset of HYK was described as early onset (first HYK event within the first 2 wk postpartum) and late onset (first HYK event in wk 3 to 6 postpartum). The effect of ketosis status on blood glucose within 42 DIM was evaluated using a generalized linear mixed model. No effect was observed of HYK on glucose concentration in primiparous cows. Multiparous cows with early-onset HYK had a lower glucose concentration (-0.21 mmol/L) compared with nonketotic cows. Overall, primiparous cows had a lower prevalence and incidence of hypoglycemia than multiparous cows. Hypoglycemia in multiparous cows was associated with higher first test-day milk production and 100 DIM milk production. In conclusion, hypoglycemia mainly occurred in multiparous cows with early-onset HYK, whereas primiparous cows were at a lower risk for hypoglycemia. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  8. Water immersion in preeclampsia.

    Science.gov (United States)

    Elvan-Taşpinar, Ayten; Franx, Arie; Delprat, Constance C; Bruinse, Hein W; Koomans, Hein A

    2006-12-01

    Preeclampsia is associated with profound vasoconstriction in most organ systems and reduced plasma volume. Because water immersion produces a marked central redistribution of blood volume and suppresses the renin-angiotensin system response and sympathetic activity, we hypothesized that water immersion might be useful in the treatment of preeclampsia. The effects of thermoneutral water immersion for 3 hours on central and peripheral hemodynamics were evaluated in 7 preeclamptic patients, 7 normal pregnant control patients, and 7 nonpregnant women. Finger plethysmography was used to determine hemodynamic measurements (cardiac output and total peripheral resistance), and forearm blood flow was measured by strain gauge plethysmography. Postischemic hyperemia was used to determine endothelium-dependent vasodilation. Analysis was by analysis of variance for repeated measurements. During water immersion cardiac output increased while diastolic blood pressure and heart rate decreased, although systolic blood pressure remained unchanged in each group. Forearm blood flow increased significantly in the normal pregnant and preeclamptic subjects. Total peripheral resistance decreased in all groups, but values in preeclamptic patients remained above those of normotensive pregnant women. Water immersion had no effect on endothelium-dependent vasodilation in the preeclamptic group, and most hemodynamic changes that were observed reversed to baseline within 2 hours of completion of the procedure. Although water immersion results in hemodynamic alterations in a manner that is theoretically therapeutic for women with preeclampsia, the effect was limited and short-lived. In addition water immersion had no effect on endothelium-dependent vasodilation in women with preeclampsia. The therapeutic potential for water immersion in preeclampsia appears to be limited.

  9. Interleukins in preeclampsia

    International Nuclear Information System (INIS)

    Olusi, Samuel O.; Diejomahoh, M.; Omu, A.; Abdulaziz, A.; Prabha, K.; George, S.

    2000-01-01

    Preeclampsia is a multisystemic disorder of unknown etiology. Recently,endothelial damage has been implicated in its cause. The objective of thisstudy was to determine the role of interleukins in the etiology ofpreeclampsia. 32 primigravidas with preeclampsia but without any clinicalevidence of infection and 32 age-matched primigravidas with uncomplicatednormal pregnancies were investigated. Phlebotomy was performed at 32 weeks ofgestation and blood collected for immunoassay of interleukin-2 (IL-2),interleukin-2 receptor (IL-2R), interleukin-6 (IL-6), interleukin-8 (IL-8)andvinterleukin-10 (IL-10), using commercially available immunoassay kits.Although the maternal plasma concentrations of IL-2 and IL-2R were slightlyhigher in normal pregnant women (76.3+-13.7 pg/mL and 526+-47.1pg/mL,respectively) than in women with preeclampsia (57.8+-1.08 pg/mL and476.9+-3.9pg/mL, respectively), the difference was not statistically significant(P>0.05). However, maternal plasma IL-6 and IL-8 concentrations weresignificantly higher (P<0.05) in normal pregnancy (158.0+-35.4 pg/mL and5163.6+- 800pg/mL, respectively) than in pregnancy complicated withpreeclampsia (60.0+-13.7 pg/mL and 2495.8+-729 pg/mL, respectively). On thepther hand, maternal plasma concentration of IL-10 was significantly higher(P<0.05) in preeclampsia (93.2+-24.1 pg/mL) than in normal pregnancy(31.0+-7.0 pg/mL). It is concluded that the elevated maternal plasma IL-10concentration in preeclampsia may be protective response to maternalimmunorejection. (author)

  10. Molecular Features and Methylation Status in Early Onset (≤40 Years Colorectal Cancer: A Population Based, Case-Control Study

    Directory of Open Access Journals (Sweden)

    Giulia Magnani

    2015-01-01

    Full Text Available Colorectal cancer is usually considered a disease of the elderly. However, a small fraction of patients develops colorectal cancer earlier. The aim of our study was to define the frequency of known hereditary colorectal syndromes and to characterise genetic and epigenetic features of early nonhereditary tumors. Thirty-three patients ≤40 years with diagnosis of colorectal cancer and 41 patients with disease at >60 years of age were investigated for MSI, Mismatch Repair proteins expression, KRAS and BRAF mutations, hypermethylation, and LINE-1 hypomethylation. Detection of germline mutations was performed in Mismatch Repair, APC and MUTYH genes. Early onset colorectal cancer showed a high incidence of hereditary forms (18%. KRAS mutations were detected in 36% of early nonhereditary tumors. Early onset colorectal cancer disclosed an average number of methylated genes significantly lower when compared to the controls (p=0.02. Finally both of the two groups were highly methylated in ESR1, GATA5, and WT1 genes and were similar for LINE-1 hypomethylation. The genetic make-up of carcinomas differs from young to elderly patients. Early onset tumors showed more frequently a constitutional defective of Mismatch Repair System and a minor number of methylated genes. Hypermethylation of ESR1, GATA5, and WT1 genes suggests possible markers in the earlier diagnosis of colorectal tumorigenesis.

  11. Early drinking onset: a study of prevalence and determinants among 13-year-old adolescents in Norway.

    Science.gov (United States)

    Adolfsen, Frode; Strøm, Henriette Kyrrestad; Martinussen, Monica; Natvig, Henrik; Eisemann, Martin; Handegård, Bjørn Helge; Koposov, Roman

    2014-10-01

    Early drinking onset is associated with different psychosocial adjustment problems among adolescents. The aim of this study was to assess determinants associated with early drinking and to identify factors predicting early drinking onset among adolescents. The study included 1,550 eighth-graders with a mean age of 13.5 years from 41 schools. A total of 24% (boys 29%, girls 19%) had ever drunk alcohol, while 14% had drunk some alcohol in the last 30 days. Further, early drinking was associated with gender, religion, school performance, smoking and bullying in the bivariate tests. Predictors of early drinking onset were identified by generalized linear mixed models with two multivariable models created. The first model included social and environmental variables. Entering intentions, expectancies, attitudes and norms into the multivariable analysis resulted in a significant improvement of the model fit constituting 86% in the second model. The percentage correctly classified those (56%) who had been drinking in the second model which was two times higher compared to the first model. Gender, religion and smoking emerged as significant predictors of drinking in both models. © 2014 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

  12. Comparison of microbial pattern in early and late onset neonatal sepsis in referral center Haji Adam Malik hospital Medan Indonesia

    Science.gov (United States)

    Hasibuan, B. S.

    2018-03-01

    Neonatal sepsis contributes a significant rate of infants mortality and morbidity. The pathogens are diverse from region to another and change time to time even in the same place. To analyze the microbial pattern in early and late onset neonatal sepsis andthe pattern of antibiotic resistance of the causative microbes at one of referral center hospital in Indonesia, Haji Adam Malik Hospital, a cross-sectional descriptive study was conducted on neonates with sepsis diagnosis proven with positive blood culture within one year period (2015-2016). Among 626 neonates admitted to perinatology unit, the total of 154 neonates was proven to have neonatal sepsis with positive blood culture with the incidence rate 24.6%. Seventy-nine (51.3%) neonates were diagnosed with early onset sepsis while 75 (48,7%) neonates had late-onset sepsis. Klebsiella pneumonia was the most commonly isolated organism in both early and late onset sepsis, encompassing 19.5% of cases. Periodic surveillance of the causative agents of neonatal sepsis is needed to implement the rational, empirical choice of antibiotic prescription while waiting for blood culture result to come out.

  13. Hepatocyte nuclear factor 1-alpha mutation in normal glucose-tolerant subjects and early-onset type 2 diabetic patients

    OpenAIRE

    Lim, Dong Mee; Huh, Nam; Park, Keun Yong

    2008-01-01

    Background/Aims The prevalence of diabetes in Korea is reported to be approximately 10%, but cases of maturity-onset diabetes of the young (MODY) are rare in Korea. A diagnostic technique for autosomal dominant MODY is being actively sought. In this regard, we used a DNA chip to investigate the frequency of mutations of the MODY3 gene (hepatocyte nuclear factor-1?) in Korean patients with early-onset type 2 diabetes. Methods The genomic DNA of 30 normal individuals [age, 24.9?8.6 years] and 2...

  14. Early-onset baldness and the risk of aggressive prostate cancer: findings from a case-control study.

    Science.gov (United States)

    Papa, Nathan P; MacInnis, Robert J; English, Dallas R; Bolton, Damien; Davis, Ian D; Lawrentschuk, Nathan; Millar, Jeremy L; Severi, Gianluca; Hopper, John L; Giles, Graham G

    2018-01-01

    We aimed to evaluate the associations between androgenetic alopecia at a young age and subsequent development of aggressive prostate cancer (PC). Using a case-control design with self-administered questionnaire, we evaluated the association between aggressive PC and very early-onset balding at age 20, and early-onset balding at age 40 years in 1,941 men. Cases were men with high-grade and/or advanced stage cancer and controls were clinic based men who had undergone biopsy and were found to be histologically cancer negative. Additionally, for cases we assessed whether early-onset balding was associated with earlier onset of disease. Men with very early-onset balding at age 20 years were at increased risk for subsequent aggressive PC [odds ratio (OR) 1.51, 95% confidence interval (CI) 1.07-2.12] after adjustment for age at baseline, family history of PC, smoking status, alcohol intake, body shape, timing of growth spurt and ejaculatory frequency. Additionally, these men were diagnosed with PC approximately 16 months earlier than cases without the exposure. The effect was present particularly for men with advanced stage pT3+ disease (OR 1.68, 95% CI 1.14-2.47) while men with organ-confined high-grade (8-10) PC did not exhibit the same relationship. No significant associations were observed for men who were balding at age 40 years, given no balding at age 20. Men with androgenetic alopecia at age 20 years are at increased risk of advanced stage PC. This small subset of men are potentially candidates for earlier screening and urological follow-up.

  15. Results of the spine-to-rib-cage distraction in the treatment of early onset scoliosis

    Directory of Open Access Journals (Sweden)

    Teli Marco

    2010-01-01

    Full Text Available Background: Growing rod systems have been used in the last 30 years for the treatment of early onset scoliosis (EOS with variable success rates. We report the results of treatment of EOS with a newly developed hybrid rod distraction system applied to the rib cage and spine with a nonfusion technique in a prospective multicenter clinical trial. Materials and Methods: A total of 22 patients affected by progressive EOS resistant to cast and/or brace treatment were enrolled from 2004 to 2005 after informed consent into a trial of surgical treatment with a single spine-to-rib growing rod instrumentation growing spine profiler (GSP. Curves> 60° Cobb in the frontal plane or bending < 50% were addressed with staged anterior annulotomy and fusion and posterior implantation of a GSP rod. Less severe and rigid curves were treated with posterior implantation of GSP only. The elongation of GSP was planned according to spinal growth. Patients were kept in a brace between elongations. Results: A total of 20 patients were available to follow-up with complete data. The mean follow up is 4.1 years. Mean age at time of initial surgery was 5 years (3-8. Nine patients had staged antero-posterior surgeries, 11 posterior only surgeries. Mean spinal growth was 1.9 cm (1.5-2.3 or 0.5 cm per year. Mean coronal Cobb′s angle correction was from 56° to 45°. Major complications affected 40% of patients and included rod failure in 6/20 and crankshaft in 5/20 (all in the anteroposterior surgery group. Conclusion: Treatment of EOS with spine-to-rib growing rod in the present form provides similar correction and complication rates to those published in the series considering traditional single or dual growing rod systems. Based on this, the authors recommend revision of the GSP design and a new clinical trial to test safety and efficacy.

  16. Cord Blood Acute Phase Reactants Predict Early Onset Neonatal Sepsis in Preterm Infants.

    Directory of Open Access Journals (Sweden)

    Leena B Mithal

    Full Text Available Early onset sepsis (EOS is a major cause of morbidity and mortality in preterm infants, yet diagnosis remains inadequate resulting in missed cases or prolonged empiric antibiotics with adverse consequences. Evaluation of acute phase reactant (APR biomarkers in umbilical cord blood at birth may improve EOS detection in preterm infants with intrauterine infection.In this nested case-control study, infants (29.7 weeks gestation, IQR: 27.7-32.2 were identified from a longitudinal cohort with archived cord blood and placental histopathology. Patients were categorized using culture, laboratory, clinical, and antibiotic treatment data into sepsis groups: confirmed sepsis (cEOS, n = 12; presumed sepsis (PS, n = 30; and no sepsis (controls, n = 30. Nine APRs were measured in duplicate from cord blood using commercially available multiplex immunoassays (Bio-Plex Pro™. In addition, placental histopathologic data were linked to biomarker results.cEOS organisms were Escherichia coli, Streptococcus agalactiae, Proteus mirabilis, Haemophilus influenzae and Listeria monocytogenes. C-reactive protein (CRP, serum amyloid A (SAA, haptoglobin (Hp, serum amyloid P and ferritin were significantly elevated in cEOS compared to controls (p<0.01. SAA, CRP, and Hp were elevated in cEOS but not in PS (p<0.01 and had AUCs of 99%, 96%, and 95% respectively in predicting cEOS. Regression analysis revealed robust associations of SAA, CRP, and Hp with EOS after adjustment for covariates. Procalcitonin, fibrinogen, α-2-macroglobulin and tissue plasminogen activator were not significantly different across groups. Placental acute inflammation was associated with APR elevation and was present in all cEOS, 9 PS, and 17 control infants.This study shows that certain APRs are elevated in cord blood of premature infants with EOS of intrauterine origin. SAA, CRP, and Hp at birth have potential diagnostic utility for risk stratification and identification of infants with EOS.

  17. Older adults in jail: high rates and early onset of geriatric conditions.

    Science.gov (United States)

    Greene, Meredith; Ahalt, Cyrus; Stijacic-Cenzer, Irena; Metzger, Lia; Williams, Brie

    2018-02-17

    The number of older adults in the criminal justice system is rapidly increasing. While this population is thought to experience an early onset of aging-related health conditions ("accelerated aging"), studies have not directly compared rates of geriatric conditions in this population to those found in the general population. The aims of this study were to compare the burden of geriatric conditions among older adults in jail to rates found in an age-matched nationally representative sample of community dwelling older adults. This cross sectional study compared 238 older jail inmates age 55 or older to 6871 older adults in the national Health and Retirement Study (HRS). We used an age-adjusted analysis, accounting for the difference in age distributions between the two groups, to compare sociodemographics, chronic conditions, and geriatric conditions (functional, sensory, and mobility impairment). A second age-adjusted analysis compared those in jail to HRS participants in the lowest quintile of wealth. All geriatric conditions were significantly more common in jail-based participants than in HRS participants overall and HRS participants in the lowest quintile of net worth. Jail-based participants (average age of 59) experienced four out of six geriatric conditions at rates similar to those found in HRS participants age 75 or older. Geriatric conditions are prevalent in older adults in jail at significantly younger ages than non-incarcerated older adults suggesting that geriatric assessment and geriatric-focused care are needed for older adults cycling through jail in their 50s and that correctional clinicians require knowledge about geriatric assessment and care.

  18. Kita driven expression of oncogenic HRAS leads to early onset and highly penetrant melanoma in zebrafish.

    Directory of Open Access Journals (Sweden)

    Cristina Santoriello

    2010-12-01

    Full Text Available Melanoma is the most aggressive and lethal form of skin cancer. Because of the increasing incidence and high lethality of melanoma, animal models for continuously observing melanoma formation and progression as well as for testing pharmacological agents are needed.Using the combinatorial Gal4-UAS system, we have developed a zebrafish transgenic line that expresses oncogenic HRAS under the kita promoter. Already at 3 days transgenic kita-GFP-RAS larvae show a hyper-pigmentation phenotype as earliest evidence of abnormal melanocyte growth. By 2-4 weeks, masses of transformed melanocytes form in the tail stalk of the majority of kita-GFP-RAS transgenic fish. The adult tumors evident between 1-3 months of age faithfully reproduce the immunological, histological and molecular phenotypes of human melanoma, but on a condensed time-line. Furthermore, they show transplantability, dependence on mitfa expression and do not require additional mutations in tumor suppressors. In contrast to kita expressing melanocyte progenitors that efficiently develop melanoma, mitfa expressing progenitors in a second Gal4-driver line were 4 times less efficient in developing melanoma during the three months observation period.This indicates that zebrafish kita promoter is a powerful tool for driving oncogene expression in the right cells and at the right level to induce early onset melanoma in the presence of tumor suppressors. Thus our zebrafish model provides a link between kita expressing melanocyte progenitors and melanoma and offers the advantage of a larval phenotype suitable for large scale drug and genetic modifier screens.

  19. [Early onset pneumonia after successful resuscitation : Incidence after mild invasive hypothermia therapy].

    Science.gov (United States)

    Erath, J W; Hodrius, J; Bushoven, P; Fichtlscherer, S; Zeiher, A M; Seeger, F H; Honold, J

    2017-09-01

    Targeted temperature management (TTM) represents an effective therapy to improve neurologic outcome in patients who survive an out-of-hospital cardiac arrest (OHCA). First publications about this therapy reported a higher incidence of infections in patients who underwent TTM induced by external cooling devices. Whether intravascular cooling devices are also associated with an increased infection rate has not been investigated so far. In a single center retrospective study, the incidence of early onset pneumonia (EOP) in OHCA patients with or without intravascular TTM at 33 °C target temperature for 24 h who survived at least 24 h after admission was analyzed. A total of 68 OHCA survivors (mean age 65 ± 15 years) were included in this analysis. The most common causes of OHCA were myocardial infarction (35 %), primary ventricular fibrillation (24 %), asystole (15 %), and pulmonary embolism (7 %). Of those, 32 patients (48 %) received TTM. The overall incidence of EOP was 38 %. Incidence of EOP did not differ significantly between groups, was more frequent in the group without TTM (42 % vs. 34 %, p = 0.57) and had no impact on mortality (hazard ratio = 1.02; 95 % confidence interval 0.25-4.16; p = 0.97). Intravascular TTM at 33 °C with a cooling catheter is not associated with more infective complications in OHCA patients. This finding underscores the safety of TTM.

  20. The Effect of Growing Rod Treatment on Hemoglobin and Hematocrit Levels in Early-onset Scoliosis.

    Science.gov (United States)

    Barrett, Kody K; Lee, Christopher; Myung, Karen; Johnston, Charles; Shah, Suken A; Akbarnia, Behrooz A; Skaggs, David L

    2016-09-01

    This study examines preoperative hemoglobin (Hgb) and hematocrit (Hct) levels in a group of early-onset scoliosis (EOS) patients and the effect of distraction-based growing rods (GRs) on these levels. Children with EOS are at risk for respiratory insufficiency and chronic hypoxemia. Increased Hgb and Hct levels have been identified as surrogate markers for chronic hypoxemia. A study of patients who underwent VEPTR surgery showed a significant decrease in Hgb levels following surgery. Data were retrospectively collected on 66 EOS patients without confounding respiratory issues or oxygen dependence who were treated with GRs at 5 institutions. Average age at initial surgery was 5.5 years. Patients were followed for a minimum of 2 years (average 3.7 y). Preoperative and postoperative Hgb and Hct levels were converted to Z-scores based on age-adjusted mean blood indices and were compared using a paired t test. The prevalence of elevated Hgb and Hct levels (Z-score >2) preoperatively was 15% (10/66) and 19% (12/64), respectively. The average Hgb Z-score decreased from 0.20 to -0.31 (P=0.005) 6 to 24 months following surgery and the Hct Z-score decreased from 0.31 to -0.28 (P=0.002) 6 to 24 months following surgery. Following distraction-based GR treatment of children with EOS there was a significant decrease in both their Hgb and Hct. This is a physiological marker of decreased hypoxemia and improved pulmonary function. Level III-therapeutic study.

  1. Early-onset and classical forms of type 2 diabetes show impaired expression of genes involved in muscle branched-chain amino acids metabolism

    DEFF Research Database (Denmark)

    Hernández-Alvarez, María Isabel; Díaz-Ramos, Angels; Berdasco, María

    2017-01-01

    The molecular mechanisms responsible for the pathophysiological traits of type 2 diabetes are incompletely understood. Here we have performed transcriptomic analysis in skeletal muscle, and plasma metabolomics from subjects with classical and early-onset forms of type 2 diabetes (T2D). Focused...... of type 2 diabetes, and this occurs both in early-onset and in classical type 2 diabetes....

  2. The Potential Contribution of BRCA Mutations to Early Onset and Familial Breast Cancer in Uzbekistan.

    Science.gov (United States)

    Abdikhakimov, Abdulla; Tukhtaboeva, Mukaddas; Adilov, Bakhtiyar; Turdikulova, Shahlo

    2016-01-01

    Breast cancer is the most common malignancy in women and affects approximately 1 out of 8 females in the US. Risk of developing breast cancer is strongly influenced by genetic factors. Germ-line mutations in BRCA1 and BRCA2 genes are associated with 5-10% of breast cancer incidence. To reduce the risk of developing cancer and to increase the likelihood of early detection, carriers of BRCA1 or BRCA2 mutations are offered surveillance programs and effective preventive medical interventions. Identification of founder mutations of BRCA1/2 in high risk communities can have a significant impact on the management of hereditary cancer at the level of the national healthcare systems, making genetic testing more affordable and cost-effective. BRCA1 and BRCA2 mutations in breast cancer patients have not been characterized in the Uzbek population. This pilot study aimed to investigate the contribution of BRCA1 and BRCA2 mutation to early onset and familial cases of breast cancer in Uzbekistan. A total of 67 patients with breast cancer and 103 age-matched disease free controls were included in this study. Utilizing SYBR Green based real-time allele-specific PCR, we have analyzed DNA samples of patients with breast cancer and disease free controls to identify the following BRCA1 and BRCA2 mutations: BRCA1 5382insC, BRCA1 4153delA, BRCA1 185delAG, BRCA1 300T>G, BRCA2 6174delT. Three unrelated samples (4.5%) were found to be positive for the heterozygous 5382insCBRCA1 mutation, representing a possible founder mutation in the Uzbek population, supporting the need for larger studies examining the contribution of this mutation to breast cancer incidence in Uzbekistan. We did not find BRCA1 4153delA, BRCA1 185delAG, BRCA1 300T>G, and BRCA2 6174delT mutations. This preliminary evidence suggests a potential contribution of BRCA1 5382insC mutation to breast cancer development in Uzbek population. Taking into account a high disease penetrance in carriers of BRCA1 mutation, it seems

  3. Temporal-lobe morphology differs between healthy adolescents and those with early-onset of depression

    Directory of Open Access Journals (Sweden)

    Mahdi Ramezani

    2014-01-01

    Full Text Available Major depressive disorder (MDD has previously been linked to structural changes in several brain regions, particularly in the medial temporal lobes (Bellani, Baiano, Brambilla, 2010; Bellani, Baiano, Brambilla, 2011. This has been determined using voxel-based morphometry, segmentation algorithms, and analysis of shape deformations (Bell-McGinty et al., 2002; Bergouignan et al., 2009; Posener et al., 2003; Vasic et al., 2008; Zhao et al., 2008: these are methods in which information related to the shape and the pose (the size, and anatomical position and orientation of structures is lost. Here, we incorporate information about shape and pose to measure structural deformation in adolescents and young adults with and without depression (as measured using the Beck Depression Inventory and Diagnostic and Statistical Manual of Mental Disorders criteria. As a hypothesis-generating study, a significance level of p < 0.05, uncorrected for multiple comparisons, was used, so that subtle morphological differences in brain structures between adolescent depressed individuals and control participants could be identified. We focus on changes in cortical and subcortical temporal structures, and use a multi-object statistical pose and shape model to analyze imaging data from 16 females (aged 16–21 and 3 males (aged 18 with early-onset MDD, and 25 female and 1 male normal control participants, drawn from the same age range. The hippocampus, parahippocampal gyrus, putamen, and superior, inferior and middle temporal gyri in both hemispheres of the brain were automatically segmented using the LONI Probabilistic Brain Atlas (Shattuck et al., 2008 in MNI space. Points on the surface of each structure in the atlas were extracted and warped to each participant's structural MRI. These surface points were analyzed to extract the pose and shape features. Pose differences were detected between the two groups, particularly in the left and right putamina, right hippocampus

  4. Comparison between Early-Onset and Late-Onset Alzheimer's Disease Patients with Amnestic Presentation: CSF and 18F-FDG PET Study

    Directory of Open Access Journals (Sweden)

    Agostino Chiaravalloti

    2016-04-01

    Full Text Available Background/Aims: To investigate the differences in brain glucose consumption between patients with early onset of Alzheimer's disease (EOAD, aged ≤65 years and patients with late onset of Alzheimer's disease (LOAD, aged >65 years. Methods: Differences in brain glucose consumption between the groups have been evaluated by means of Statistical Parametric Mapping version 8, with the use of age, sex, Mini-Mental State Examination and cerebrospinal fluid values of Aβ1-42, phosphorylated Tau and total Tau as covariates in the comparison between EOAD and LOAD. Results: As compared to LOAD, EOAD patients showed a significant decrease in glucose consumption in a wide portion of the left parietal lobe (BA7, BA31 and BA40. No significant differences were obtained when subtracting the EOAD from the LOAD group. Conclusions: The results of our study show that patients with EOAD show a different metabolic pattern as compared to those with LOAD that mainly involves the left parietal lobe.

  5. Comparison between Early-Onset and Late-Onset Alzheimer's Disease Patients with Amnestic Presentation: CSF and 18F-FDG PET Study

    Science.gov (United States)

    Chiaravalloti, Agostino; Koch, Giacomo; Toniolo, Sofia; Belli, Lorena; Lorenzo, Francesco Di; Gaudenzi, Sara; Schillaci, Orazio; Bozzali, Marco; Sancesario, Giuseppe; Martorana, Alessandro

    2016-01-01

    Background/Aims To investigate the differences in brain glucose consumption between patients with early onset of Alzheimer's disease (EOAD, aged ≤65 years) and patients with late onset of Alzheimer's disease (LOAD, aged >65 years). Methods Differences in brain glucose consumption between the groups have been evaluated by means of Statistical Parametric Mapping version 8, with the use of age, sex, Mini-Mental State Examination and cerebrospinal fluid values of AΒ1-42, phosphorylated Tau and total Tau as covariates in the comparison between EOAD and LOAD. Results As compared to LOAD, EOAD patients showed a significant decrease in glucose consumption in a wide portion of the left parietal lobe (BA7, BA31 and BA40). No significant differences were obtained when subtracting the EOAD from the LOAD group. Conclusions The results of our study show that patients with EOAD show a different metabolic pattern as compared to those with LOAD that mainly involves the left parietal lobe. PMID:27195000

  6. Early-onset stroke with moyamoya-like syndrome and extraneurological signs: a first reported paediatric series

    International Nuclear Information System (INIS)

    Law-ye, Bruno; Saliou, Guillaume; Toulgoat, Frederique; Tardieu, Marc; Deiva, Kumaran; Adamsbaum, Catherine; Husson, Beatrice

    2016-01-01

    Moyamoya syndrome is characterised by an occlusion of the carotid terminations with the development of collateral vessels. Our objective is to describe a series of infants presenting early-onset moyamoya-like syndrome, which may constitute a distinct entity. From a cohort of children with rare cerebral vascular pathologies, we studied eight infants (28 days-1 year) with early-onset moyamoya-like syndrome demonstrated by angiography. We retrospectively analysed the patterns on MRI and MRA, as well as all other available data. Median age at diagnosis was 7 months (IQR: 6-8) with arterial ischaemic stroke in the middle cerebral artery territory. All of the children experienced severe stroke recurrence within a median time of 11 months (IQR: 10-12), and all showed extraneurological symptoms. The anterior cerebral circulation was involved in all cases and the posterior circulation was involved in six. Two children died and all of the other children suffered permanent neurological deficits. The presence of extraneurological signs in cases of early-onset moyamoya syndrome is suggestive of a newly described systemic vasculopathy with predominantly cerebrovascular expression. Given its rapid progression marked by severe recurrent strokes and poor clinical outcome, early diagnosis could help in the decision to institute aggressive therapy. (orig.)

  7. Is Early-onset in Major Depression a Predictor of Specific Clinical Features with More Impaired Social Function?

    Science.gov (United States)

    Liu, Yan-Hong; Chen, Lin; Su, Yun-Ai; Fang, Yi-Ru; Srisurapanont, Manit; Hong, Jin Pyo; Hatim, Ahmad; Chua, Hong Choon; Bautista, Dianne; Si, Tian-Mei

    2015-01-01

    Background: Early-onset major depressive disorder (MDD) (EOD) is often particularly malignant due to its special clinical features, accompanying impaired social function, protracted recovery time, and frequent recurrence. This study aimed to observe the effects of age onset on clinical characteristics and social function in MDD patients in Asia. Methods: In total, 547 out-patients aged 18–65 years who were from 13 study sites in five Asian countries were included. These patients had MDD diagnose according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria. Clinical features and social function were assessed using Symptom Checklist-90-revised (SCL-90-R) and Sheehan Disability Scale (SDS). Quality of life was assessed by a 36-item Short-form Health Survey (SF-36). Analyses were performed using a continuous or dichotomous (cut-off: 30 years) age-of-onset indicator. Results: Early-onset MDD (EOD, <30 years) was associated with longer illness (P = 0.003), unmarried status (P < 0.001), higher neuroticism (P ≤ 0.002) based on the SCL-90-R, and more limited social function and mental health (P = 0.006, P = 0.007) based on the SF-36 and SDS. The impairment of social function and clinical severity were more prominent at in-patients with younger onset ages. Special clinical features and more impaired social function and quality of life were associated with EOD, as in western studies. Conclusions: EOD often follows higher levels of neuroticism. Age of onset of MDD may be a predictor of clinical features and impaired social function, allowing earlier diagnosis and treatment. PMID:25758278

  8. Is Early-onset in Major Depression a Predictor of Specific Clinical Features with More Impaired Social Function?

    Institute of Scientific and Technical Information of China (English)

    Yan-Hong Liu; Lin Chen; Yun-Ai Su; Yi-Ru Fang; Manit Srisurapanont; Jin Pyo Hong; Ahmad Hatim

    2015-01-01

    Background:Early-onset major depressive disorder (MDD) (EOD) is often particularly malignant due to its special clinical features,accompanying impaired social function,protracted recovery time,and frequent recurrence.This study aimed to observe the effects of age onset on clinical characteristics and social function in MDD patients in Asia.Methods:In total,547 out-patients aged 18-65 years who were from 13 study sites in five Asian countries were included.These patients had MDD diagnose according to the Diagnostic and Statistical Manual of Mental Disorders,4th Edition criteria.Clinical features and social function were assessed using Symptom Checklist-90-revised (SCL-90-R) and Sheehan Disability Scale (SDS).Quality of life was assessed by a 36-item Short-form Health Survey (SF-36).Analyses were performed using a continuous or dichotomous (cut-off:30 years)age-of-onset indicator.Results:Early-onset MDD (EOD,<30 years) was associated with longer illness (P =0.003),unmarried status (P < 0.001),higher neuroticism (P ≤ 0.002) based on the SCL-90-R,and more limited social function and mental health (P =0.006,P =0.007) based on the SF-36 and SDS.The impairment of social function and clinical severity were more prominent at in-patients with younger onset ages.Special clinical features and more impaired social function and quality of life were associated with EOD,as in western studies.Conclusions:EOD often follows higher levels of neuroticism.Age of onset of MDD may be a predictor of clinical features and impaired social function,allowing earlier diagnosis and treatment.

  9. Risk factors for pre-eclampsia among women at antenatal booking in Kano, Northern Nigeria

    Directory of Open Access Journals (Sweden)

    Ibrahim A. Yakasai

    2013-05-01

    Full Text Available Pre-eclampsia (PE is an important cause of maternal mortality. There have been several studies on risk factors assessment with conflicting reports across the globe on this disease; however, rigorous recent evaluation of these factors is uncommon in this region. The aim of the present study was to determine the risks factors in the early-onset PE in Aminu Kano Teaching Hospital (AKTH, Kano (Northern Nigeria. We conducted a case-control study in Nigeria between April 2009 and January 2010 to identify the risk factors associated with the early-onset PE in women attending antenatal clinic in AKTH. Information on socio-cultural characteristics, medical history, previous obstetrics