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Sample records for early-onset streptococcal infection

  1. Detection of anti-streptococcal, antienolase, and anti-neural antibodies in subjects with early-onset psychiatric disorders.

    Science.gov (United States)

    Nicolini, Humberto; López, Yaumara; Genis-Mendoza, Alma D; Manrique, Viana; Lopez-Canovas, Lilia; Niubo, Esperanza; Hernández, Lázaro; Bobes, María A; Riverón, Ana M; López-Casamichana, Mavil; Flores, Julio; Lanzagorta, Nuria; De la Fuente-Sandoval, Camilo; Santana, Daniel

    2015-01-01

    Infection with group A Streptococcus (StrepA) can cause post-infectious sequelae, including a spectrum of childhood-onset obsessive-compulsive (OCD) and tic disorders with autoimmune origin (PANDAS, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections). Until now, no single immunological test has been designed that unequivocally diagnoses these disorders. In this study, we assessed the detection of serum antibodies against human brain enolase (AE), neural tissue (AN) and Streptococcus (AS) as a laboratory tool for the diagnosis of early-onset psychiatric disorders. Serum antibodies against human brain enolase, total brain proteins, and total proteins from StrepA were detected by ELISA in 37 patients with a presumptive diagnosis of PANDAS and in 12 healthy subjects from Mexico and Cuba. The antibody titers against human brain enolase (AE) and Streptococcal proteins (AS) were higher in patients than in control subjects (t-student, tAE=-2.17, P=0.035; tAS=-2.68, P=0.01, n=12 and 37/group, df=47, significance level 0.05), while the neural antibody titers did not differ between the two groups (P(t)=0.05). The number of subjects (titers> meancontrol + CI95) with simultaneous seropositivity to all three antibodies was higher in the patient group (51.4%) than in the control group (8.3%) group (X2=5.27, P=0.022, df=1, n=49). The simultaneous detection of all three of these antibodies could provide valuable information for the etiologic diagnosis of individuals with early-onset obsessive-compulsive disorders associated with streptococcal infection and, consequently, for prescribing suitable therapy.

  2. The prevention of early-onset neonatal group B streptococcal disease.

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    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

  3. Early-onset group B streptococcal disease following culture-based screening in Japan: a single center study.

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    Miyata, Akane; Takahashi, Hironori; Kubo, Takahiko; Watanabe, Noriyoshi; Tsukamoto, Keiko; Ito, Yushi; Sago, Haruhiko

    2012-08-01

    We investigated trends in early-onset group B streptococcal disease (EOD) after the introduction of culture-based screening in Japan. A retrospective cohort study examined EOD trends in 9506 pregnancies and 10 715 neonates at our center from 2002 to 2009. EOD occurred in four neonates (4/7332: 0.55/1000 live births). The EOD incidence among infants born to women positive for GBS by screening was 0.90 cases per 1000 live births (1/1107). In contrast, the EOD incidence among infants negative by GBS screening was 0.48 cases per 1000 live births (3/6225). Thus, of the four affected neonates, three had mothers who tested negative on antepartum GBS screening. Two neonates had symptoms of infection during labor and intrapartum antibiotic agents were administered. The other two neonates received no antibiotics because deliveries were uneventful and they were negative on GBS screening. The incidence of EOD is 0.90 cases per 1000 live births among GBS-positive women and 0.48 cases per 1000 live births among GBS-negative women. The results of our study implied that EOD can develop regardless of GBS screening and intrapartum clinical course, although the method of sample collection, indications for antibiotic prophylaxis, and the antibiotics regimen should be considered. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

  4. Is neonatal group B streptococcal infection preventable?

    LENUS (Irish Health Repository)

    Azam, M

    2011-05-01

    Early onset group B streptococcal (EOGBS) infection causes significant neonatal morbidity and mortality. We determined the incidence of EOGBS at Galway University Hospital (GUH) and examined any "missed opportunities" for preventing neonatal infection between 2004 and 2009. Our obstetric approach is risk-based. The incidence was 0.45\\/1,000 live-births; one death and one with neurological sequelae. A single mother received IAP; however we could not determine any potential for reducing cases of EOGBS by improving current IAP usage.

  5. [Successful continuous renal replacement therapy in a neonate with early-onset group B streptococcal sepsis and multi-organ dysfunction syndrome].

    Science.gov (United States)

    von Schnakenburg, C; Hufnagel, M; Superti-Furga, A; Rieger-Fackeldey, E; Berner, R

    2009-01-01

    Group B streptococcal early-onset sepsis (GBS EOS) in neonates has a mortality rate of approximately 5%, particularly in the presence of multi-organ dysfunction. Fluid management is crucial in these patients, and continuous venovenous haemofiltration (CVVH) should be considered a therapeutic option even in newborn babies. After an uneventful pregnancy within hours after birth, a female term infant presented with dyspnoea, irritability and cyanosis. The systemic inflammatory response syndrome (SIRS) progressed to multi-organ dysfunction with acute respiratory distress syndrome (ARDS), impaired myocardial contractility, pulmonary hypertension and fluid overload. The maximum PRISM score was 51. The child required maximal respiratory and inotropic support with high volume intravenous fluid administration. However, only by using of CVVH from day 5 to 14, we successfully resolved progressive pulmonary and cardiovascular dysfunction. The child improved directly after initiation of fluid removal, was extubated on day 17 and discharged without obvious sequelae on day 57. All microbiology studies revealed GBS. Perinatal GBS-infections remain a major life-threatening event for newborn babies. CVVH should be considered an option for reversing fluid overload even in neonates with overwhelming SIRS. Alternatively, extracorporeal membrane oxygenation (ECMO) is discussed.

  6. Tics, OCD and Streptococcal Infection (PANDAS

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    J Gordon Millichap

    2008-07-01

    Full Text Available Forty matched pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS case-control pairs were prospectively evaluated clinically and with testing for group A b-hemolytic streptococcus for an average of 2 years, in a study at University of Rochester School of Medicine, New York; and WHO Streptococcal Reference Laboratory, Minneapolis, MN.

  7. Association of streptococcal throat infection with mental disorders

    DEFF Research Database (Denmark)

    Orlovska, Sonja; Vestergaard, Claus Hostrup; Bech, Bodil Hammer

    2017-01-01

    IMPORTANCE Streptococcal infection has been linked with the development of obsessive-compulsive disorder (OCD) and tic disorders, a concept termed pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). However, previous studies of this association have b...

  8. Maternal and neonatal risk factors for early-onset group B streptococcal disease: a case control study

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    Al-Kadri HM

    2013-10-01

    Full Text Available Hanan M Al-Kadri,1 Samira S Bamuhair,2 Sameera M Al Johani,3 Namsha A Al-Buriki,1 Hani M Tamim4 1Department of Obstetrics and Gynecology, 2Department of Basic Medical Sciences, 3Microbiology Division, 4Department of Medical Education, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia Objectives: To identify the prominent maternal and neonatal risk factors associated with early-onset group B streptococcus (EOGBS disease in neonates and to determine their importance by comparing them with a control group. Setting: Neonatal unit at King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia. Patients: Cases were infants <7 days of age with invasive group B streptococcus (GBS disease diagnosed between January 1, 2000 and December 31, 2009. Controls were healthy infants born in the same hospital during the same period having the same birth weight and gestational age category. Main outcome measures: Maternal risk factors for developing EOGBS disease, feto–maternal and neonatal clinical data, their morbidities, mortalities, and length of hospital stay. Results: A total of 99 cases and 200 controls were included. The majority of cases presented in the first 72 hours of life (62/99 [63.9%], of which 87/99 (89.7% had at least one clinical risk factor for the development of EOGBS disease. Mothers of neonates with EOGBS disease were more likely to have GBS bacteriuria (odds ratio [OR] 10.76, 95% confidence interval [CI] 1.24–93.42, infection in the peripartum period (OR 8.92, CI 2.87–27.68, and temperature ≥38°C (OR 7.10, CI 2.50–20.17. GBS disease was associated with premature rupture of membranes and fetal tachycardia (P<0.01 for both. Neonates with EOGBS disease were more likely to have respiratory distress disease and convulsions, require tube feeding, and have longer hospital stays compared with the controls (P<0.01 for all. Stepwise multiple logistic

  9. 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.

  10. Analysis of early-onset bloodstream infection due to Escherichia coli infection in premature babies

    OpenAIRE

    Chen, I-Lun; Huang, Hsin-Chun; Wu, Chih-Te; Ou-Yang, Mei-Chen; Chung, Mei-Yung; Chen, Chih-Cheng; Suen, Jau-Ling; Hung, Chih-Hsing

    2017-01-01

    Abstract In early-onset bacteremia among preterm neonates, Escherichia coli (E. coli) is the main pathogen and can cause a high mortality rate. Thus, the predictive factors of mortality and extended-spectrum ?-lactamase (ESBL)-producing E. coli in preterm babies with E. coli early-onset bacteremia were reported. We retrospectively reviewed preterm neonates who had E. coli bacteremia occurring within 3 days after birth between 2004 and 2015. Maternal and perinatal information were collected fr...

  11. 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

  12. Early-onset invasive aspergillosis and other fungal infections in patients treated with ibrutinib.

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    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.

  13. Invasive Group A Streptococcal Infection

    Centers for Disease Control (CDC) Podcasts

    2011-06-13

    In this podcast, CDC's Dr. Chris Van Beneden discusses the dangers of group A strep infections.  Created: 6/13/2011 by National Center for Emerging Zoonotic and Infectious Diseases (NCEZID).   Date Released: 6/13/2011.

  14. Risk of early-onset neonatal infection with maternal infection or colonization: a global systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Grace J Chan

    2013-08-01

    Full Text Available Neonatal infections cause a significant proportion of deaths in the first week of life, yet little is known about risk factors and pathways of transmission for early-onset neonatal sepsis globally. We aimed to estimate the risk of neonatal infection (excluding sexually transmitted diseases [STDs] or congenital infections in the first seven days of life among newborns of mothers with bacterial infection or colonization during the intrapartum period.We searched PubMed, Embase, Scopus, Web of Science, Cochrane Library, and the World Health Organization Regional Databases for studies of maternal infection, vertical transmission, and neonatal infection published from January 1, 1960 to March 30, 2013. Studies were included that reported effect measures on the risk of neonatal infection among newborns exposed to maternal infection. Random effects meta-analyses were used to pool data and calculate the odds ratio estimates of risk of infection. Eighty-three studies met the inclusion criteria. Seven studies (8.4% were from high neonatal mortality settings. Considerable heterogeneity existed between studies given the various definitions of laboratory-confirmed and clinical signs of infection, as well as for colonization and risk factors. The odds ratio for neonatal lab-confirmed infection among newborns of mothers with lab-confirmed infection was 6.6 (95% CI 3.9-11.2. Newborns of mothers with colonization had a 9.4 (95% CI 3.1-28.5 times higher odds of lab-confirmed infection than newborns of non-colonized mothers. Newborns of mothers with risk factors for infection (defined as prelabour rupture of membranes [PROM], preterm <37 weeks PROM, and prolonged ROM had a 2.3 (95% CI 1.0-5.4 times higher odds of infection than newborns of mothers without risk factors.Neonatal infection in the first week of life is associated with maternal infection and colonization. High-quality studies, particularly from settings with high neonatal mortality, are needed to

  15. Puerperal and intrapartum group A streptococcal infection.

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    Anteby, E Y; Yagel, S; Hanoch, J; Shapiro, M; Moses, A E

    1999-01-01

    OBJECTIVE: To determine the demographic and clinical variables characteristic of non-epidemic intrapartum or puerperal group A streptococcal (GAS) infection. METHODS: The records of 47 patients diagnosed with intrapartum or puerperal GAS infection over a 6 1/2 year period at Hadassah-University Hospital-Mt. Scopus, Jerusalem were reviewed. Data regarding 25,811 women, the general population of women that delivered during that period, were obtained from their computerized medical records. Frequency distributions, t-test, chi-square, and Spearman's Rank Correlation were used, as appropriate, to analyze and compare demographic and clinical variables associated with development of GAS infection, its clinical course and subsequent development of septic shock. RESULTS: Mean age of mothers with GAS infection was higher than that of our general pregnant population (30.4 versus 27.4 years, P = 0.0019), and a higher proportion of GAS infected patients (30% versus 12%, P < 0.005) experienced PROM. Thirty-one (66%) women had fever as their sole presenting symptom, eight (17%) had fever and abdominal pain, seven (15%) had fever and abnormal vaginal bleeding, and one patient (2%) presented with a rash. Three patients (6%) developed a septic shock. Two of these patients presented with symptoms more than 14 days after delivery. CONCLUSIONS: We describe the characteristics of non-epidemic intrapartum or puerperal GAS infection. Data from our study and review of the literature suggest that some patients who develop septic shock may present later in the puerperium than patients with an uncomplicated GAS infection. PMID:10598916

  16. Evaluation of serum chemokine RANTES concentration as a biomarker in the diagnosis of early-onset severe infections in neonates

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    Małgorzata Stojewska

    2016-04-01

    Full Text Available Objective: Only a few studies on improving the early diagnosis of severe neonatal infections have focused on the role of serum RANTES concentration (sRC. The aim of the study was to establish sRC in neonates with early-onset infections, according to their gestational age, sex, birth asphyxia, mode of delivery and value of some biochemical and hematological parameters.Material/Methods: The analysis comprised 129 neonates, including 89 infected (52 preterm, 37 full-term; 43 with sepsis, 39 with congenital pneumonia, 7 with severe urinary tract infection and 40 healthy (control group, 25 full-term, 15 preterm. The sRC in peripheral vein blood was measured by the ELISA method using Quantikine Set (R & D systems, USA.Results: The sRC in infected neonates ranged from 10.83 to 122.55 μg/ml, in full-term neonates from 18.28 to 122.55 μg/ml, and in preterm from 10.83 to 118.24 μg/ml. The mean sRCs in full-term septic neonates (73.95±25.99 μg/ml and with organ infections (58.43±29.24 μg/ml were significantly higher than healthy ones (28.25±14.06 μg/ml. The mean sRCs in septic preterm neonates (59.17±28.29 μg/ml and those with organ infections (50.86±28.16 were significantly higher than in healthy preterm neonates (25.61±8.29 μg/ml. Positive correlations between sRC and CRP value (r=0.3014, p=0.004 and between sRC and band cell count (r=0.2489, p=0.019 were found in all infected neonates. Conclusion. The significant increase of serum RANTES concentration in early-onset infections in neonates, regardless of their gestational age, sex and birth asphyxia, not only proves the presence of an active immunological process but also may be a useful biomarker for diagnosis of severe neonatal infections.

  17. [Group B streptococcal early-onset neonatal sepsis in the area of Barcelona (2004-2010). Analysis of missed opportunities for prevention].

    Science.gov (United States)

    Giménez, Montserrat; Sanfeliu, Isabel; Sierra, Montserrat; Dopico, Eva; Juncosa, Teresa; Andreu, Antonia; Lite, Josep; Guardià, Cèlia; Sánchez, Ferran; Bosch, Jordi

    2015-01-01

    To study the evolution of the incidence of early-onset neonatal sepsis (EOS) by Streptococcus agalactiae in the area of Barcelona and to analyze failure of compliance with the prevention protocol. A retrospective review was carried out on EOS cases in 8 Health-Care Centers in the Barcelona area between 2004 and 2010. Forty-nine newborns from 48 mothers were diagnosed with EOS. The incidence was 0.29‰ living newborns (0.18-0.47‰), with no significant differences in the fluctuations along the 7 years. The mortality rate was 8.16%. In 68.5% cases the maternal colonization studies were negative, and in 21% these studies were not performed. No risk factors were detected in 58.3% of pregnant women, and 22.9% of births were premature. In 58% of cases intra-partum antibiotic prophylaxis was not administered because it was not indicated, and in 42% due to failure to follow the protocol (3 strains were resistant to erythromycin). Resistance to clindamycin was 33.3%. The Streptococcus agalactiae serotypes more frequently isolated were iii, v, and ia. No significant changes were detected in the incidence of Streptococcus agalactiae EOS in the 7 years of the study. The increased sensitivity of screening methods with the use of molecular techniques, the performance of susceptibility testing of strains isolated from pregnant women, and the improvement of communication between Health-Care Centers, can contribute to a better implementation of the protocol, as well as to reduce the incidence of EOS. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  18. Should Israel screen all mothers-to-be to prevent early-onset of neonatal group B streptococcal disease? A cost-utility analysis

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    Ginsberg Gary M

    2013-02-01

    Full Text Available Abstract Background In Israel, an average of 37 children are born each year with sepsis and another four with meningitis as a result of Group B Streptococcal (GBS disease. Israel currently only screens mothers with defined risk factors (around 15% of all pregnancies in order to identify candidates for Intrapartum Antiobiotic Prophyhlaxis (IAP of GBS. This paper presents a cost-utility analysis of implementing an alternative strategy, which would expand the current protocol to one aiming to screen all pregnant women at 35–37 weeks gestation based on taking a vaginal culture for GBS. Methods A spreadsheet model was built incorporating technical, epidemiological, health service costs, demographic and economic data based primarily on Israeli sources. Results The intervention of universal screening (compared with the current scenario would increase screening costs from 580,000 NIS to 3,278,000 million NIS. In addition, the intervention would also increase penicillin costs from 39,000 NIS to 221,000 NIS. Current culture screening of approximately 15% of mothers-to-be with high risk factors resulted in 42 GBS births in 2008-9 (0.253/1000 births. Expanding culture screening to 85% of mothers-to-be, will decrease the number of GBS births to 17.3 (0.104/1000 births. The initial 2.9 million NIS incremental intervention costs are offset by decreased treatment costs of 1.9 million NIS and work productivity gains of 811,000 NIS as a result of a decrease in neurological sequelae from GBS caused meningitis. Thus the resultant net cost of the intervention is only around 134,000 NIS. Culture based screening will reduce the burden of disease by 12.6 discounted Quality Adjusted Life Years (QALYS, giving a very cost effective baseline incremental cost per QALY (cf. risk factor screening of 10,641 NIS per QALY. The data was very sensitive to rates of anaphylactic shock and changes in the percentage of meningitis cases that had associated long term

  19. Should Israel screen all mothers-to-be to prevent early-onset of neonatal group B streptococcal disease? A cost-utility analysis.

    Science.gov (United States)

    Ginsberg, Gary M; Eidelman, Arthur I; Shinwell, Eric; Anis, Emilia; Peyser, Reuven; Lotan, Yoram

    2013-02-20

    In Israel, an average of 37 children are born each year with sepsis and another four with meningitis as a result of Group B Streptococcal (GBS) disease. Israel currently only screens mothers with defined risk factors (around 15% of all pregnancies) in order to identify candidates for Intrapartum Antiobiotic Prophyhlaxis (IAP) of GBS. This paper presents a cost-utility analysis of implementing an alternative strategy, which would expand the current protocol to one aiming to screen all pregnant women at 35-37 weeks gestation based on taking a vaginal culture for GBS. A spreadsheet model was built incorporating technical, epidemiological, health service costs, demographic and economic data based primarily on Israeli sources. The intervention of universal screening (compared with the current scenario) would increase screening costs from 580,000 NIS to 3,278,000 million NIS. In addition, the intervention would also increase penicillin costs from 39,000 NIS to 221,000 NIS. Current culture screening of approximately 15% of mothers-to-be with high risk factors resulted in 42 GBS births in 2008-9 (0.253/1000 births). Expanding culture screening to 85% of mothers-to-be, will decrease the number of GBS births to 17.3 (0.104/1000 births). The initial 2.9 million NIS incremental intervention costs are offset by decreased treatment costs of 1.9 million NIS and work productivity gains of 811,000 NIS as a result of a decrease in neurological sequelae from GBS caused meningitis. Thus the resultant net cost of the intervention is only around 134,000 NIS. Culture based screening will reduce the burden of disease by 12.6 discounted Quality Adjusted Life Years (QALYS), giving a very cost effective baseline incremental cost per QALY (cf. risk factor screening) of 10,641 NIS per QALY. The data was very sensitive to rates of anaphylactic shock and changes in the percentage of meningitis cases that had associated long term-sequelae. It is recommended that Israel adopt universal culture

  20. Management of guttate psoriasis in patients with associated streptococcal infection

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    Karabudak Abuaf O

    2012-11-01

    Full Text Available Özlem Karabudak Abuaf, Bilal DoganDepartment of Dermatology, GATA Haydarpasa Teaching Hospital, Istanbul, TurkeyAbstract: Psoriasis is a T cell-mediated inflammatory skin disease. It can be provoked or exacerbated by environmental factors, particularly medications and infections. Guttate psoriasis is a distinctive acute form of psoriasis that generally occurs in children and young adults. The association between guttate psoriasis and Streptococcus pyogenes is well established in medical literature; however, the exact mechanism can only be theorized. Treatment guidelines are not established, and it is unclear how necessary antibiotics are for acute state guttate psoriasis. Many dermatologists have recommended using antibiotic therapy or tonsillectomy, especially for patients with recurrent streptococcal infections. This paper briefly summarizes the possible mechanisms of pathogenesis and the recent research results on this topic and examines under what conditions a curative treatment of streptococcal infection by tonsillectomy or antibiotic treatment may benefit psoriasis patients.Keywords: guttate, psoriasis, treatment, Streptococcus pyogenes

  1. The association between maternal cervicovaginal proinflammatory cytokines concentrations during pregnancy and subsequent early-onset neonatal infection.

    Science.gov (United States)

    Kalinka, Jarosław; Krajewski, Paweł; Sobala, Wojciech; Wasiela, Małgorzata; Brzezińska-Błaszczyk, Ewa

    2006-01-01

    The aim of this study was to investigate the relationship between the concentration of selected proinflammatory cytokines (IL-1alpha, IL-1beta, IL-6 and IL-8) in cervicovaginal fluid, as measured in midgestation, and the risk of early-onset neonatal infection (EONI). Cervicovaginal fluids were obtained from a cohort of 114 pregnant women at 22 to 34 weeks' gestation. The samples were analyzed for the concentrations of selected proinflammatory cytokines using standard enzyme-linked immunosorbent assay technique (ELISA). Lower genital tract microbiology was diagnosed using Gram stain method according to Spiegel's criteria and by culture. Mean gestational age at the time of sampling was 29.0 weeks. Mean time between sampling and delivery was 9.3 (SD 4.7) weeks. Bacterial vaginosis (BV) was diagnosed in 27.2% of subjects and M. hominis and U. urealyticum in 22.8% and 26.3%, respectively. Out of 114 women examined, 20 (17.5%) delivered newborns with EONI. Median cervicovaginal concentrations of IL-1alpha, IL-1beta, IL-6 and IL-8 did not differ between women who delivered newborns with EONI as compared to women who delivered newborns without EONI. Women with pathological lower genital tract microflora and low IL-8 concentration (below 25(th) percentile) during pregnancy presented a significant risk of delivering newborns with EONI (OR=4.9; 95% CI, 1.1-22.8). Subjects with pathological lower genital tract microflora and a low concentration of more than one cytokine had the highest risk of delivering a newborn with EONI, OR=16.2, 95% CI, 1.1-234.0. Cytokine measurement in cervicovaginal fluid in early gestation could be useful for predicting subsequent EONI only among pregnant women with lower genital tract infection. Maternal genital tract immune hyporesponsiveness as represented by low concentrations of proinflammatory cytokines may create a permissive environment for ascending infection and may lead to subsequent EONI.

  2. Streptococcal Infections: Not A or B

    Science.gov (United States)

    ... non-GAS and non-GBS infections can cause urinary tract infections, inflammation of the heart’s lining (endocarditis), respiratory tract ... newborns, as well as other infections such as urinary tract infections in older children. The most prevalent enterococci species ...

  3. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections: Role of Otolaryngologist

    Directory of Open Access Journals (Sweden)

    Emrah Kara

    2015-03-01

    Full Text Available Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, refers to a disorder in children who manifest symptoms of obsessive-compulsive disorder and/or tic disorders associated with acute exacerbations. Although autoimmune responses following infections with streptococcus have been hypothesized to be responsible, there is still controversies about the pathophysiology and treatment. In this article, the treatment methods of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections and the role of otolaryngologist were discussed.

  4. Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections (PANDAS): Experience at a Tertiary Referral Center

    OpenAIRE

    Singer, Harvey S.

    2015-01-01

    The entity Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS) was initially proposed in 1998 (Swedo, et al. 1998). The formal diagnosis required that the affected individual meet five specific criteria: prepubertal onset, obsessive compulsive disorder (OCD) and/or a tic disorder, the dramatic sudden explosive onset of symptoms, a relapsing and remitting course of symptoms that are temporally associated with Group A beta-hemolytic streptococcal (G...

  5. Barriers to implementing the NICE guidelines for early-onset neonatal infection: cross-sectional survey of neonatal blood culture reporting by laboratories in the UK.

    Science.gov (United States)

    Paul, S P; Caplan, E M; Morgan, H A; Turner, P C

    2018-04-01

    The National Institute for Health and Care Excellence published guidelines for managing early-onset neonatal infections in 2012. It recommended provision for reporting blood cultures (BCs) with growth detected or not detected at 36 h. To determine if this was followed, a telephone survey was conducted amongst lead biomedical scientists based at microbiology laboratories (N = 209) in the UK. Overall, 202/209 responded and 139/202 had on-site facilities for BCs. BC results with growth detected or not detected at 36 h were available out-of-hours in 36/139 (26.6%) and 66/139 (47.5%) neonatal units, respectively. Early discontinuation of antibiotics should lead to improved antibiotic stewardship. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  6. 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...

  7. [A postpartum woman with toxic shock syndrome: group A streptococcal infection, a much feared postpartum complication.

    NARCIS (Netherlands)

    Abbink, K.; Kortekaas, J.C.; Buise, M.P.; Dokter, J.; Kuppens, S.M.; Hasaart, T.H.M.

    2016-01-01

    BACKGROUND: The development of toxic shock syndrome (TSS) after an invasive group A streptococcal (GAS) infection in the postpartum period is a much feared complication. The mortality rate of TSS with necrotizing fasciitis is 30 to 50%. CASE DESCRIPTION: We present the case of a woman with atypical

  8. Paedatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection in an Indian Adolescent--A Case Report

    Science.gov (United States)

    Sharma, Sachin; Vaish, Supriya; Chopra, Saurabh; Singh, Vindyaprakash; Sharma, Priyanka

    2012-01-01

    Pediatric Autoimmune Neuropsychiatric Disorders associated with Streptococcal infection (PANDAS) is a unique constellation of signs and symptoms that exist in a subset of children with rapid onset or exacerbation of obsessive-compulsive disorder (OCD) and/or tic disorders due to an initial autoimmune reaction to a Group A Beta Hemolytic…

  9. 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...

  10. 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)

  11. [Severe late-onset group B streptococcal infection. A case report].

    Science.gov (United States)

    Haase, Roland; Nagel, Frank; Hirsch, Wolfgang; Sitka, Uwe

    2003-01-01

    Group B Streptococcus (GBS) is a well-known cause of neonatal pneumonia, sepsis and meningitis. Peripartal antibiotic prophylaxis for early-onset GBS infection is in routine use since the beginning of the last decade, but strategies for effective prevention of late-onset GBS infections are still lacking. Few hours after discharge from a non-local maternity ward a 3-week-old boy was admitted to our hospital because of GBS meningitis with necrotizing encephalomalacia. Maternal mastitis, not a disease of the baby, had led to the first admission. Case history and negative maternal swabs and cultures for GBS led to the hypothesis of nosocomial infection. Screening and risk based peripartal antibiotic prophylaxis, better monitoring and improved therapeutic modalities have reduced the incidence and mortality of early-onset GBS infections, but peripartal prophylaxis failed to influence late-onset GBS infections. Up to 40 % of infants with late-onset meningitis develop neurological sequelae. Maternal vaccination with multivalent conjugate vaccines against GBS is a new strategy which may lead to passive protection of the infant. Further studies to examine the efficacy of vaccines are in progress.

  12. [Therapeutic response to plasmapheresis in four cases with obsessive-compulsive disorder and tic disorder triggered by streptococcal infections].

    Science.gov (United States)

    Beşiroğlu, Lütfullah; Ağargün, Mehmet Yücel; Ozbebit, Ozgür; Sözen, Mehmet; Dilek, Imdat; Güleç, Mustafa

    2007-01-01

    The acronym PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) has been assigned to a subgroup of patients experiencing pediatric onset obsessive-compulsive symptoms and tics as a result of autoimmune response to group A beta-hemolytic streptococcal infection. It has been hypothesized that an immune process initiated by infection affects the basal ganglia and causes neuropsychiatric symptoms. In cases with severe neuropsychiatric symptoms, the use of treatment strategies that interrupt the autoimmune process responsible for the pathogenesis of PANDAS, such as therapeutic plasmapheresis or intravenous immunoglobulin, has been proposed. In this paper, we discuss the effect of plasmapheresis treatment in 4 adult cases of obsessive-compulsive disorder and tic disorder triggered by streptococcal infections.

  13. Biofilm in group A streptococcal necrotizing soft tissue infections

    DEFF Research Database (Denmark)

    Siemens, Nikolai; Chakrakodi, Bhavya; Shambat, Srikanth Mairpady

    2016-01-01

    Necrotizing fasciitis caused by group A streptococcus (GAS) is a life-threatening, rapidly progressing infection. At present, biofilm is not recognized as a potential problem in GAS necrotizing soft tissue infections (NSTI), as it is typically linked to chronic infections or associated with forei...

  14. The prevalence of asymptomatic group B streptococcal infection and ...

    African Journals Online (AJOL)

    pathogen because it can cause bovine mastitis in dairy cows. The species ... Clinical trials have demonstrated that administering intravenous ... mortality is a challenge in most African settings and infection ..... include ethnic and genetic factors.

  15. [Group B streptococcal perinatal infection] [Article in Italian] • Infezione perinatale da Streptococco Gruppo B

    Directory of Open Access Journals (Sweden)

    Giampiero Capobianco

    2014-01-01

    Full Text Available The bacterium group B Streptococcus (GBS is the leading cause of neonatal bacterial infection in developed countries. GBS is a Gram positive bacterium located primarly in the gastrointestinal tract and genitourinary system. The presentation of GBS neonatal disease includes pneumonia, respiratory distress and meningitis. The newborn is colonized during passage through the birth canal. The mother, when colonized, is usually asymptomatic. GBS is present in the vagina of about 10-15% of women towards the end of pregnancy. During the first 7 days of life (early onset infection about 3% of the colonized children develop the infection, especially meningitis, that may be fatal or leave sequelae; this infection predominantly results from vertical transmission of GBS from colonized mothers during the intrapartum period. Infection of GBS from one week to 90 days of age (late onset infection results from transmission after birth. In Italy, according to national guidelines of pregnancy 2011, a culture-based screening approach is performed: all patients are screened for vaginal and rectal GBS between 36 and 37 weeks of gestation and if found positive are then treated with prophylactic antibiotics during labor. Intravenous intrapartum antibiotic prophylaxis (IAP in women who carry GBS, from the onset of labour until delivery (given ≥ 4 hours before delivery, reduces the risk of early onset neonatal GBS infection from 4.7% to 0.4%. Pe nicillin G is the antibiotic of choice. In case of pe nicillin allergy, erythromicin or clindamycin are generally active against GBS and carry no particular risks for the infant.Articoli Selezionati del “3° Convegno Pediatrico del Medio Campidano” · Guspini · 25 Maggio 2013 Guest Editor: Roberto Antonucci

  16. Identity of streptococcal blood isolates and oral isolates from two patients with infective endocarditis

    DEFF Research Database (Denmark)

    Fiehn, N E; Gutschik, E; Larsen, Tove

    1995-01-01

    The purpose of this study was to isolate streptococcal strains from the oral cavities of streptococcal endocarditis patients and compare these strains biochemically and genetically with the corresponding streptococcal blood isolates. Total identity was observed between the blood and oral cavity...

  17. Streptococcal Upper Respiratory Tract Infections and Exacerbations of Tic and Obsessive-Compulsive Symptoms: A Prospective Longitudinal Study

    Science.gov (United States)

    Leckman, James F.; King, Robert A.; Gilbert, Donald L.; Coffey, Barbara J.; Singer, Harvey S.; Dure, Leon S., IV; Grantz, Heidi; Katsovich, Liliya; Lin, Haiqun; Lombroso, Paul J.; Kawikova, Ivana; Johnson, Dwight R.; Kurlan, Roger M.; Kaplan, Edward L.

    2011-01-01

    Objective: The objective of this blinded, prospective, longitudinal study was to determine whether new group A beta hemolytic streptococcal (GABHS) infections are temporally associated with exacerbations of tic or obsessive-compulsive (OC) symptoms in children who met published criteria for pediatric autoimmune neuropsychiatric disorders…

  18. Clinical presentation of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections in research and community settings.

    Science.gov (United States)

    Swedo, Susan E; Seidlitz, Jakob; Kovacevic, Miro; Latimer, M Elizabeth; Hommer, Rebecca; Lougee, Lorraine; Grant, Paul

    2015-02-01

    The first cases of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) were described >15 years ago. Since that time, the literature has been divided between studies that successfully demonstrate an etiologic relationship between Group A streptococcal (GAS) infections and childhood-onset obsessive-compulsive disorder (OCD), and those that fail to find an association. One possible explanation for the conflicting reports is that the diagnostic criteria proposed for PANDAS are not specific enough to describe a unique and homogeneous cohort of patients. To evaluate the validity of the PANDAS criteria, we compared clinical characteristics of PANDAS patients identified in two community practices with a sample of children meeting full research criteria for PANDAS. A systematic review of clinical records was used to identify the presence or absence of selected symptoms in children evaluated for PANDAS by physicians in Hinsdale, Illinois (n=52) and Bethesda, Maryland (n=40). RESULTS were compared against data from participants in National Institute of Mental Health (NIMH) research investigations of PANDAS (n=48). As described in the original PANDAS cohort, males outnumbered females (95:45) by ∼ 2:1, and symptoms began in early childhood (7.3±2.7 years). Clinical presentations were remarkably similar across sites, with all children reporting acute onset of OCD symptoms and multiple comorbidities, including separation anxiety (86-92%), school issues (75-81%), sleep disruptions (71%), tics (60-65%), urinary symptoms (42-81%), and others. Twenty of the community cases (22%) failed to meet PANDAS criteria because of an absence of documentation of GAS infections. The diagnostic criteria for PANDAS can be used by clinicians to accurately identify patients with common clinical features and shared etiology of symptoms. Although difficulties in documenting an association between GAS infection and symptom onset/exacerbations may

  19. Study of role of streptococcal throat infection in pityriasis rosea

    Directory of Open Access Journals (Sweden)

    Parija Madhuri

    2008-01-01

    Full Text Available Background: Pityriasis rosea is a common, acute exanthem of uncertain etiology. The exact cause of pityriasis rosea is not known but various hypotheses have been postulated incriminating infective agents such as viruses, bacteria, spirochete and noninfective etiologies such as atopy and autoimmune causes have also been investigated. Aim: We undertook a study to investigate the role of Streptococcus haemolyticus in the causation of pityriasis rosea and study the levels of C-reactive protein (CRP and ASLO titer in patients with pityriasis rosea. Materials and Methods: The study included 20 patients with pityriasis rosea attending the outpatient dermatology department at JIPMER hospital during the period from June to December 2004. Corresponding number of age- and sex-matched controls were chosen from amongst healthy individuals and patients attending skin OPD with dermatological disorders other than pityriasis rosea. Results: On analyzing the data collected from 20 cases of pityriasis rosea, the average age was found to be 15.3 years and ranged from 5 years to 30 years. The male to female ratio was found to be 1.5:1. The average duration of illness was 14.5 days (median and 29.3 days (mean. CRP was negative in all the cases as well as the controls. ASLO titer was found to be raised in 2 (10% cases, while it remained below the critical value in all the controls. On comparing the cases and controls, the raised ASLO titer in the cases was found to be not statistically significant (p = 0.147. From the throat swab culture, Streptococcus haemolyticus was isolated from only one case and none of the controls. This finding was not statistically significant (p = 0.310. Conclusion: As per the findings of the present study, we arrived at conclusion that there is no association between streptococcus pharyngitis and pityriasis rosea.

  20. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS: An Evolving Concept

    Directory of Open Access Journals (Sweden)

    Antonella Macerollo

    2013-09-01

    Full Text Available Pediatric autoimmune neuropsychiatric disorders associated with streptococcus infections (PANDAS originated from the observational work of Swedo and collaborators, who formalized their definition in 1998 in a set of operational criteria. The application of these criteria, which focuses on tics and obsessive-compulsive symptoms as core symptoms, has encountered difficulties, eventually leading to a high rate of misdiagnosis. In particular, the core feature represented by the association between newly diagnosed infections and neuropsychiatric symptom relapses in youths with this diagnosis could not be demonstrated by longitudinal studies. Exploratory studies aiming to identify clinical or cognitive features that could discriminate PANDAS from other pediatric obsessive-compulsive and tic disorders present methodological limitations, and therefore are not conclusive. Other behavioral features, in addition to obsessive-compulsive symptoms and tics, have been included in pediatric acute-onset neuropsychiatric syndromes (PANS and childhood acute neuropsychiatric syndromes (CANS, two new concepts recently proposed in order to define a much broader clinical spectrum encompassing etiologically diverse entities. Given the uncertainties on the clinical definition of PANDAS, it is not surprising that evidence in support of a post-infectious, immune-mediated pathophysiology is also insufficient. Anti-dopamine receptor antibodies might be relevant to both Sydenham’s chorea (SC—the prototypical post-streptococcal neuropsychiatric disorder—and some rare forms of encephalitis targeting the basal ganglia specifically, but studies exploring their association with children fulfilling Swedo’s criteria for PANDAS have been inconclusive. Moreover, we lack evidence in favor of the efficacy of antibiotic prophylaxis or tonsillectomy in patients fulfilling Swedo’s criteria for PANDAS, whereas a response to immune-mediated treatments like intravenous

  1. 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 ...

  2. Prevention and treatment strategy in pregnant women with group B streptococcal infection.

    Science.gov (United States)

    Tevdorashvili, G; Tevdorashvili, D; Andghuladze, M; Tevdorashvili, M

    2015-04-01

    Group B streptococcus (GBS; Streptococcus agalactiae) are encapsulated gram-positive cocci belonging to Lancefield group B, that frequently colonizes the human genital and gastrointestinal tracts. It is an important cause of illness in three categories of population: infants, pregnant women, and adults with underlying medical conditions. In pregnant women and postpartum women, GBS is a frequent cause of asymptomatic bacteriuria, urinary tract infection, upper genital tract infection (i.e. intraamniotic infection or chorioamnionitis), postpartum endometritis (8%), pneumonia (2%), puerperal sepsis (2%), and bacteremia without a focal site (31%). It also can cause focal infections such as pneumonia, meningitis, and endocarditis, albeit rarely. Invasive maternal infection with GBS is associated with pregnancy loss and preterm delivery. Prior to the widespread use of maternal intrapartum chemoprophylaxis, maternal colonization with GBS conferred an increased risk of chorioamnionitis, and early postpartum infection. The serotype distribution of invasive GBS infection in pregnant women is similar to that of early-onset neonatal disease. The most common GBS serotypes causing invasive disease in adults and neonates are Ia, Ib, III, and V. Vaccination of adolescent women is considered an ideal solution. However, recent reports (April 2015) have shown that serotype IV GBS is emerging in pregnant carriers and causing infections in neonates and adults. This emergence is of concern because GBS conjugate vaccines that are being developed to prevent invasive disease may protect only against serotypes Ia, Ib, II, III, and V, or combinations thereof. Though research for the development of such a vaccine is underway, a good candidate vaccine has yet to surface.

  3. Clinical Presentation of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections in Research and Community Settings

    Science.gov (United States)

    Seidlitz, Jakob; Kovacevic, Miro; Latimer, M. Elizabeth; Hommer, Rebecca; Lougee, Lorraine; Grant, Paul

    2015-01-01

    Abstract Background: The first cases of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) were described>15 years ago. Since that time, the literature has been divided between studies that successfully demonstrate an etiologic relationship between Group A streptococcal (GAS) infections and childhood-onset obsessive-compulsive disorder (OCD), and those that fail to find an association. One possible explanation for the conflicting reports is that the diagnostic criteria proposed for PANDAS are not specific enough to describe a unique and homogeneous cohort of patients. To evaluate the validity of the PANDAS criteria, we compared clinical characteristics of PANDAS patients identified in two community practices with a sample of children meeting full research criteria for PANDAS. Methods: A systematic review of clinical records was used to identify the presence or absence of selected symptoms in children evaluated for PANDAS by physicians in Hinsdale, Illinois (n=52) and Bethesda, Maryland (n=40). Results were compared against data from participants in National Institute of Mental Health (NIMH) research investigations of PANDAS (n=48). Results: As described in the original PANDAS cohort, males outnumbered females (95:45) by ∼ 2:1, and symptoms began in early childhood (7.3±2.7 years). Clinical presentations were remarkably similar across sites, with all children reporting acute onset of OCD symptoms and multiple comorbidities, including separation anxiety (86–92%), school issues (75–81%), sleep disruptions (71%), tics (60–65%), urinary symptoms (42–81%), and others. Twenty of the community cases (22%) failed to meet PANDAS criteria because of an absence of documentation of GAS infections. Conclusions: The diagnostic criteria for PANDAS can be used by clinicians to accurately identify patients with common clinical features and shared etiology of symptoms. Although difficulties in documenting an association

  4. Lyme disease and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS: an overview

    Directory of Open Access Journals (Sweden)

    Rhee H

    2012-02-01

    Full Text Available Hanna Rhee1, Daniel J Cameron21Medicine, San Diego, CA, 2Northern Westchester Hospital, Mount Kisco, NY, USAAbstract: Lyme disease (LD is a complex, multisystemic illness. As the most common vector-borne disease in the United States, LD is caused by bacterial spirochete Borrelia burgdorferi sensu stricto, with potential coinfections from agents of anaplasmosis, babesiosis, and ehrlichiosis. Persistent symptoms and clinical signs reflect multiorgan involvement with episodes of active disease and periods of remission, not sparing the coveted central nervous system. The capability of microorganisms to cause and exacerbate various neuropsychiatric pathology is also seen in pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS, a recently described disorder attributed to bacterium Streptococcus pyogenes of group A beta-hemolytic streptococcus in which neurologic tics and obsessive-compulsive disorders are sequelae of the infection. In the current overview, LD and PANDAS are juxtaposed through a review of their respective infectious etiologies, clinical presentations, mechanisms of disease development, courses of illness, and treatment options. Future directions related to immunoneuropsychiatry are also discussed.Keywords: neuroborreliosis, infection, obsessive-compulsive disorder, tic disorder, Borrelia burgdorferi, strep throat

  5. A Cluster of Paediatric Invasive Group A Streptococcal and Chicken Pox Infections

    LENUS (Irish Health Repository)

    Ó Maoldomhnaigh, C

    2018-03-01

    Group A streptococcus (GAS) causes a variety of acute clinical syndromes from pharyngitis and scarlet fever commonly seen in primary care to more severe life-threatening invasive disease. Invasive GAS, categorised into three groups - necrotising fasciitis, streptococcal toxic shock syndrome and sepsis with or without an identifiable source of infection- is a notifiable disease to the Health Protection Surveillance Centre (HPSC)1. Laboratory criteria for a confirmed case require isolation of GAS from a normally sterile site. The HPSC previously reported a marked increase in the incidence of invasive GAS infections from 1.65\\/100,000 population in 2011 to 3.65\\/100,000 in 20132. The increased incidence was notable also for a 300% increase in the proportion of invasive GAS cases in children. After a slight decrease in incidence in 20153 (2.3\\/100000), we noted a cluster of invasive GAS cases referred to the paediatric infectious disease (PID) department of Children’s University Hospital (CUH), Temple Street, in 2016. We sought to further characterise this cluster of paediatric invasive GAS infections.

  6. Group B Streptococcal infection in neonates and colonization in pregnant women: An epidemiological retrospective analysis.

    Science.gov (United States)

    Cho, Ching-Yi; Tang, Yi-Hsuan; Chen, Yu-Hsuan; Wang, Szu-Yao; Yang, Yi-Hsin; Wang, Ting-Hao; Yeh, Chang-Ching; Wu, Keh-Gong; Jeng, Mei-Jy

    2017-08-23

    Group B Streptococcus (GBS) infection is one of the major causes of neonatal morbidity and mortality. Universal GBS screening with intrapartum antibiotic prophylaxis (IAP) in pregnant women were initiated in 2012 in Taiwan. This study aimed to analyze the most recent maternal GBS colonization rate and the changes in neonatal GBS infection rate from 2011 to 2016. All pregnant women and their live born neonates between January 2011 and June 2016 were retrospectively reviewed. Whether GBS screening was done, screening results, presence of risk factors, the use of antibiotics, and neonatal outcome were analyzed. In addition, hospitalized neonates diagnosed with GBS infections were retrieved for comparison of early onset disease (EOD) (women delivered babies during the study period. The maternal GBS screening rate was 71.0% and the colonization rate was 22.6%. The overall neonatal invasive GBS infection rate was 0.81 per 1000 live births and the vertical transmission rate was 1.2%. After 2012, the invasive neonatal GBS infection rate declined from 1.1-1.6‰ to 0.6-0.7‰ in 2014 and thereafter, the GBS EOD incidence rate declined from 2.8‰ to 0.0-0.6‰, but the LOD incidence rate remained approximately 0.7‰. Infants with EOD had strong association with obstetric risk factors. Taiwan's universal GBS screening with IAP program reduced the incidence rate of neonatal GBS EOD to be lower than 1‰ after 2012. Pediatricians still should pay attention to infants with GBS LOD since its incidence rate remained unchanged. Copyright © 2017. Published by Elsevier B.V.

  7. Invasive Group A Streptococcal Infection and Vaccine Implications, Auckland, New Zealand

    Science.gov (United States)

    Safar, Atheer; Stewart, Joanna; Trenholme, Adrian; Drinkovic, Dragana; Peat, Briar; Taylor, Susan; Read, Kerry; Roberts, Sally; Voss, Lesley

    2011-01-01

    We aimed to assess the effect of invasive group A streptococcal (GAS) infection and the potential effects of a multivalent GAS vaccine in New Zealand. During January 2005–December 2006, we conducted prospective population-based laboratory surveillance of Auckland residents admitted to all public hospitals with isolation of GAS from normally sterile sites. Using emm typing, we identified 225 persons with confirmed invasive GAS infection (median 53 years of age; range 0–97 years). Overall incidence was 8.1 cases per 100,00 persons per year (20.4/100,000/year for Maori and Pacific Islanders; 24.4/100,000/year for persons >65 years of age; 33/100,000/year for infants Auckland’s lowest socioeconomic quintile. Twenty-two persons died, for an overall case-fatality rate of 10% (63% for toxic shock syndrome). Seventy-four percent of patients who died had an underlying condition. To the population in our study, the proposed 26-valent vaccine would provide limited benefit. PMID:21749758

  8. Assessment of periodontitis and its role in viridans streptococcal bacteremia and infective endocarditis

    Directory of Open Access Journals (Sweden)

    Shree Dhotre

    2018-03-01

    Full Text Available Objectives: To evaluate the role of periodontitis in viridans group streptococci (VGS bacteremia and infective endocarditis (IE. Methods: A total of 200 subjects including two groups. Group A- 34 subjects undergoing tooth extraction with periodontitis, 46 subjects undergoing tooth extraction without periodontitis and 40 healthy controls. Group B: 40 confirmed cases of IE (17 with and 23 without periodontitis and 40 healthy controls. Subgingival plaque and blood samples were obtained and processed by standard procedures. Results: A total of 53 blood samples (66.25% yielded positive cultures after tooth extraction. The relationship between the presence of periodontitis and a positive blood culture was significantly higher (p = 0.05 for tooth extraction cases with periodontitis (79.40% than tooth extraction cases without periodontitis (56.50%. Periodontitis was observed in 42.5% of IE cases. Out of the 40 patients of IE, the blood samples yielded 40 different isolates, majority were viridans streptococci 15 (37.5% and staphylococci nine (22.5%. No statistically significant difference was observed between the subgingival plaque and blood isolates of periodontitis in both the groups, indicating similarity of biotypes of viridans streptococci isolated from the blood and the subgingival plaque. Similarity was also observed between the antibiogram profiles of viridans streptococci from both the groups. Conclusions: Periodontitis enhances viridans streptococcal bacteremia and may be a potential risk factor for IE. Keywords: Infective endocarditis, Periodontitis, Viridans group streptococci

  9. 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 ...

  10. 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.

  11. Streptococcal upper respiratory tract infections and psychosocial stress predict future tic and obsessive-compulsive symptom severity in children and adolescents with Tourette syndrome and obsessive-compulsive disorder.

    Science.gov (United States)

    Lin, Haiqun; Williams, Kyle A; Katsovich, Liliya; Findley, Diane B; Grantz, Heidi; Lombroso, Paul J; King, Robert A; Bessen, Debra E; Johnson, Dwight; Kaplan, Edward L; Landeros-Weisenberger, Angeli; Zhang, Heping; Leckman, James F

    2010-04-01

    One goal of this prospective longitudinal study was to identify new group A beta-hemolytic streptococcal infections (GABHS) in children and adolescents with Tourette syndrome (TS) and/or obsessive-compulsive disorder (OCD) compared with healthy control subjects. We then examined the power of GABHS infections and measures of psychosocial stress to predict future tic, obsessive-compulsive (OC), and depressive symptom severity. Consecutive ratings of tic, OC, and depressive symptom severity were obtained for 45 cases and 41 matched control subjects over a 2-year period. Clinical raters were blinded to the results of laboratory tests. Laboratory personnel were blinded to case or control status and clinical ratings. Structural equation modeling for unbalanced repeated measures was used to assess the sequence of new GABHS infections and psychosocial stress and their impact on future symptom severity. Increases in tic and OC symptom severity did not occur after every new GABHS infection. However, the structural equation model found that these newly diagnosed infections were predictive of modest increases in future tic and OC symptom severity but did not predict future depressive symptom severity. In addition, the inclusion of new infections in the model greatly enhanced, by a factor of three, the power of psychosocial stress in predicting future tic and OC symptom severity. Our data suggest that a minority of children with TS and early-onset OCD were sensitive to antecedent GABHS infections. These infections also enhanced the predictive power of current psychosocial stress on future tic and OC symptom severity. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  12. Group B streptococcal immunisation of pregnant women for the prevention of early and late onset Group B streptococcal infection of the neonate as well as adult disease

    DEFF Research Database (Denmark)

    Kenchington, Anna L.; Lamont, Ronald F.

    2017-01-01

    of specific polyvalent vaccines continues, but testing has challenges and may require surrogate markers or molecular-based techniques to manipulate antigenicity and immunogenicity. Expert commentary: Group B streptococcal vaccination using conjugated polyvalent vaccines against the major disease causing...

  13. 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

  14. The sensitivity and the specifity of rapid antigen test in streptococcal upper respiratory tract infections.

    Science.gov (United States)

    Gurol, Yesim; Akan, Hulya; Izbirak, Guldal; Tekkanat, Zuhal Tazegun; Gunduz, Tehlile Silem; Hayran, Osman; Yilmaz, Gulden

    2010-06-01

    It is aimed to detect the sensitivity and specificity of rapid antigen detection of group A beta hemolytic streptococci from throat specimen compared with throat culture. The other goal of the study is to help in giving clinical decisions in upper respiratory tract infections according to the age group, by detection of sensitivity and positive predictive values of the rapid tests and throat cultures. Rapid antigen detection and throat culture results for group A beta hemolytic streptococci from outpatients attending to our university hospital between the first of November 2005 and 31st of December 2008 were evaluated retrospectively. Throat samples were obtained by swabs from the throat and transported in the Stuart medium and Quickvue Strep A [Quidel, San Diego, USA] cassette test was applied and for culture, specimen was inoculated on 5% blood sheep agar and identified according to bacitracin and trimethoprim-sulphametaxazole susceptibility from beta hemolytic colonies. During the dates between the first of November 2005 and 31st of December 2008, from 453 patients both rapid antigen detection and throat culture were evaluated. Rapid antigen detection sensitivity and specificity were found to be 64.6% and 96.79%, respectively. The positive predictive value was 80.95% whereas negative predictive value was 92.82%. Kappa index was 0.91. When the results were evaluated according to the age groups, the sensitivity and the positive predictive value of rapid antigen detection in children were 70%, 90.3% and in adults 59.4%, 70.4%. When bacterial infection is concerned to prevent unnecessary antibiotic use, rapid streptococcal antigen test (RSAT) is a reliable method to begin immediate treatment. To get the maximum sensitivity of RSAT, the specimen collection technique used and education of the health care workers is important. While giving clinical decision, it must be taken into consideration that the sensitivity and the positive predictive value of the RSAT is quite

  15. Group B Streptococcal Infection in Taiwan: Maternal Colonization and Neonatal Infection

    Directory of Open Access Journals (Sweden)

    Hsiu-Wen Yu

    2011-08-01

    Conclusions: We concluded that universal maternal rectovaginal culture of GBS with intrapartum antibiotic prophylaxis is an urgent call to reduce EOD and mortality because of GBS infection in neonates in Taiwan.

  16. 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....

  17. Atomoxetine Use in Attention-Deficit/Hyperactivity Disorder and Comorbid Tic Disorder in Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections.

    Science.gov (United States)

    Demirkaya, Sevcan Karakoç; Demirkaya, Mithat; Yusufoğlu, Canan; Akın, Elif

    2017-02-01

    Attention-deficit/hyperactivity disorder (ADHD) is a common comorbid disease in children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), in which tic-like involuntary movements are frequently seen clinical conditions. In contrast to psychostimulants, atomoxetine is considered as having minimal effects on tics. Here we report two cases with ADHD and PANDAS who were treated with atomoxetine for their ADHD and comorbid tics.

  18. The role of group A beta hemolytic streptococcal infections in patients with tic and tourett's disorders

    Directory of Open Access Journals (Sweden)

    Noorbakhsh S

    2010-12-01

    % PPV; Anti- streptokinase (cut off level> 332IU/ml had 34% sensitivity; 85% specificity, and 90% PPV; Anti-DNase (cut off level> 140IU/ml had 70% sensitivity; 99% specificity and PPV 90%."n"nConclusion: Patients with tic disorder had a significant high antibody titer against streptococcal infection in comparison with healthy children. It presents possible role for streptococcal infection in tic disorders. Treatment of streptococcal infection is achievable by using of long acting Penicillin in our country. Use of aggressive treatment like plasmaphresis etc needs future RCT studies.

  19. [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.

  20. 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.

  1. A clinical and bacteriologic investigation of invasive streptococcal infections in Japan on the basis of serotypes, toxin production, and genomic DNA fingerprints.

    Science.gov (United States)

    Nakashima, K; Ichiyama, S; Iinuma, Y; Hasegawa, Y; Ohta, M; Ooe, K; Shimizu, Y; Igarashi, H; Murai, T; Shimokata, K

    1997-08-01

    In a survey of invasive streptococcal infections in Japan, we analyzed isolates of Streptococcus pyogenes collected between 1992 and 1994. Genomic DNA fingerprints produced by pulsed-field gel electrophoresis (PFGE) were compared by computer-assisted analysis. Conventional serologic M types were subdivided into PFGE types showing close genetic similarity. Among the 42 isolates from patients with invasive diseases, 16 PFGE types were identified and genetic diversity was clearly demonstrated. Identical fingerprints were observed in both invasive and noninvasive isolates. Only 43% of invasive isolates produced streptococcal pyrogenic exotoxin A (SPE A), and 31% did not contain the speA gene. These findings suggest that the dissemination of a specific clone is not sufficient to explain all cases of these diseases in Japan and pose a question as to the role of SPE A as a major virulent factor. Bacterial factors other than SPE A and host factors should be considered in evaluation of the pathogenesis of the diseases.

  2. 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.

  3. 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 ...

  4. 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

  5. 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

  6. 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,

  7. Streptococcal acute pharyngitis

    Directory of Open Access Journals (Sweden)

    Lais Martins Moreira Anjos

    2014-07-01

    Full Text Available Acute pharyngitis/tonsillitis, which is characterized by inflammation of the posterior pharynx and tonsils, is a common disease. Several viruses and bacteria can cause acute pharyngitis; however, Streptococcus pyogenes (also known as Lancefield group A β-hemolytic streptococci is the only agent that requires an etiologic diagnosis and specific treatment. S. pyogenes is of major clinical importance because it can trigger post-infection systemic complications, acute rheumatic fever, and post-streptococcal glomerulonephritis. Symptom onset in streptococcal infection is usually abrupt and includes intense sore throat, fever, chills, malaise, headache, tender enlarged anterior cervical lymph nodes, and pharyngeal or tonsillar exudate. Cough, coryza, conjunctivitis, and diarrhea are uncommon, and their presence suggests a viral cause. A diagnosis of pharyngitis is supported by the patient's history and by the physical examination. Throat culture is the gold standard for diagnosing streptococcus pharyngitis. However, it has been underused in public health services because of its low availability and because of the 1- to 2-day delay in obtaining results. Rapid antigen detection tests have been used to detect S. pyogenes directly from throat swabs within minutes. Clinical scoring systems have been developed to predict the risk of S. pyogenes infection. The most commonly used scoring system is the modified Centor score. Acute S. pyogenes pharyngitis is often a self-limiting disease. Penicillins are the first-choice treatment. For patients with penicillin allergy, cephalosporins can be an acceptable alternative, although primary hypersensitivity to cephalosporins can occur. Another drug option is the macrolides. Future perspectives to prevent streptococcal pharyngitis and post-infection systemic complications include the development of an anti-Streptococcus pyogenes vaccine.

  8. [Prevention of neonatal group B streptococcal sepsis in Hungary in 2012. Preliminary data of a nation-wide survey].

    Science.gov (United States)

    Sziller, István; Szabó, Miklós; Valek, Andrea; Rigó, Barbara; Ács, Nándor

    2014-07-20

    At present, there is no obligatory guideline for the prevention of early-onset neonatal group B streptococcal disease in Hungary. The aim of the present study was to gain insight into the spontaneously developed preventive strategy of the domestic obstetric divisions and departments in Hungary. Standardized questionnaire was sent out to each of the 71 obstetric divisions and departments in Hungary. Overall, 20 (27.4%) of the chairpersons replied, and thus, 39.9% of the total number of live births in Hungary were included in the study. Despite missing public health guidelines, each of the divisions and departments developed their own strategy to prevent neonatal group B streptococcal disease. In 95% of cases, bacterial culture of the lower vagina was the method of identifying pregnant women at risk. In 5% of the cases intrapartum antibiotic prophylaxis was based on risk assessment only. Of the departments using culture-based prophylaxis, 58% departments sampled women after completion of 36th gestational weeks. Antibiotic of choice was penicillin or ampicillin in 100% of cases. Of the study participants, 80% reported on multiple administration of colonized pregnant women after onset of labor or rupture of the membranes. The authors concluded that the rate of participation in the study was low. However, prevention of early-onset neonatal group B streptococcal infection is a priority of obstetric care in Hungary. Lack of a nation-wide public health policy did not prevent obstetric institutions in this country to develop their own prevention strategy. In the majority of cases and institutions, the policy is consistent with the widely accepted international standards.

  9. 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.

  10. Comparison of clinical characteristics of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections and childhood obsessive-compulsive disorder.

    Science.gov (United States)

    Bernstein, Gail A; Victor, Andrea M; Pipal, Allison J; Williams, Kyle A

    2010-08-01

    The objectives of this study were to identify unique clinical characteristics of children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) compared with a control group of children with non-PANDAS obsessive-compulsive disorder (OCD) with respect to ancillary symptoms, types of obsessions and compulsions, symptom severity, and co-morbid DSM-IV diagnoses. Classification of PANDAS was based on review of pediatric and psychiatric records using the criteria developed by Swedo and colleagues. Children aged 6-14 with PANDAS (n = 21) and non-PANDAS OCD (n = 18) were assessed by blind independent evaluators using the PANDAS Questionnaire, Children's Yale-Brown Obsessive Compulsive Scale, Yale Global Tic Severity Scale, and Anxiety Disorders Interview Schedule for DSM-IV. PANDAS children were significantly more likely to present with separation anxiety, urinary urgency, hyperactivity, impulsivity, deterioration in handwriting, and decline in school performance during their initial episode of neuropsychiatric illness compared with children with OCD. Total tics and vocal tics were more severe in PANDAS children. Separation anxiety disorder and social phobia were more prevalent in non-PANDAS OCD children. Children with non-PANDAS OCD were significantly more likely to include others in their rituals. There were no significant differences between groups on demographics or severity of OCD. Distinguishing clinical characteristics in PANDAS, which included urinary urgency, hyperactivity, impulsivity, and deterioration in handwriting, are linked to basal ganglia functions. These clinical characteristics will aid in the differentiation of PANDAS children for research and clinical purposes and ultimately advance our understanding and treatment of this disorder.

  11. 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 ...

  12. 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.

  13. 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

  14. Genetic Architecture of Group A Streptococcal Necrotizing Soft Tissue Infections in the Mouse

    DEFF Research Database (Denmark)

    Chella Krishnan, Karthickeyan; Mukundan, Santhosh; Alagarsamy, Jeyashree

    2016-01-01

    Host genetic variations play an important role in several pathogenic diseases, and we have previously provided strong evidences that these genetic variations contribute significantly to differences in susceptibility and clinical outcomes of invasive Group A Streptococcus (GAS) infections, includi...

  15. 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.

  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. Increased cytotoxicity and streptolysin O activity in group G streptococcal strains causing invasive tissue infections

    DEFF Research Database (Denmark)

    Siemens, Nikolai; Kittang, Bård R; Chakrakodi, Bhavya

    2015-01-01

    Streptococcus dysgalactiae subsp. equisimilis (SDSE) has emerged as an important cause of severe skin and soft tissue infections, but little is known of the pathogenic mechanisms underlying tissue pathology. Patient samples and a collection of invasive and non-invasive group G SDSE strains (n = 6...

  18. Early onset mixed cryoglobulinemia in hepatitis C

    Directory of Open Access Journals (Sweden)

    Kritika Krishnamurthy

    2015-01-01

    Full Text Available Cryoglobulinemia is one of the most common forms of extrahepatic manifestation of chronic hepatitis infection. The phenomenon is generally seen after several years of chronicity predominantly in the female population resulting in arthralgias, purpuras, and other symptoms, due to vasculitis. Here we present a case of incomplete mixed cryoglobulinemia Type III (as per Brouet′s classification in a young boy aged 13 years who presented with an unusual symptom of pruritus. Diagnosis was confirmed by cryoprecipitation test followed by immunofixation. We aim to highlight the difficulty in diagnosis of this rare case/presentation, important investigation pitfalls and how to avoid them.

  19. A SKIN TEST FOR DETECTING GROUP C HEMOLYTIC STREPTOCOCCAL INFECTION CAUSING EPIZOOTIC LYMPHADENITIS IN GUINEA PIGS

    Science.gov (United States)

    Moen, Johannes K.

    1936-01-01

    1. A skin test with a crude bacterial extract prepared from group C (Lancefield) hemolytic streptococci was used as a means of detecting possible carriers of the streptococcus causing epizootic lymphadenitis in guinea pigs. A positive test similar to a positive tuberculin reaction was considered presumptive evidence of present or recent infection with this streptococcus. 2. 20 positive reactors were found in 330 supposedly normal guinea pigs. 3. 195 negatively reacting animals were used as a breeding stock which yielded 1,296 progeny over a period of 15 months. None of the breeding stock or their progeny showed evidence of spontaneous lymphadenitis. Skin tests of 100 of the progeny were all negative. 4. The use of this skin test as a means of obtaining guinea pig breeding stock free of the streptococcus causing spontaneous lymphadenitis is suggested. PMID:19870552

  20. 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

  1. An Ineffective Differential Diagnosis of Infective Endocarditis and Rheumatic Heart Disease after Streptococcal Skin and Soft Tissue Infection.

    Science.gov (United States)

    Suzuki, Tetsuya; Mawatari, Momoko; Iizuka, Toshihiko; Amano, Tatsuya; Kutsuna, Satoshi; Fujiya, Yoshihiro; Takeshita, Nozomi; Hayakawa, Kayoko; Ohmagari, Norio

    2017-09-01

    We herein report the case of a 68-year-old woman with a skin and soft tissue infection at her extremities. The blood culture results were positive for Streptococcus pyogenes, and we started treatment using ampicillin and clindamycin, although subsequent auscultation revealed a new-onset heart murmur. We therefore suspected rheumatic heart disease and infective endocarditis. The case met both the Jones criteria and the modified Duke criteria. Transesophageal echocardiography revealed vegetation on the aortic valve, although the pathological findings were also compatible with both rheumatic heart disease and infective endocarditis. The present findings suggest that these two diseases can coexist in some cases.

  2. 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

  3. 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.

  4. 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...

  5. 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…

  6. 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.

  7. 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.

  8. 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

  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. 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

  11. Post-streptococcal glomerulonephritis

    Directory of Open Access Journals (Sweden)

    Odalovic A.

    2014-01-01

    Full Text Available Post-streptococcal glomerulonephritis (PSGN is a frequent cause of acute nephritis in children. This case study was done with the aim to point out that the infections caused by Group A streptococci, in spite of antibiotic era, are still present in the population. An 8-year old boy was admitted in our hospital with a two-day history of fewer, tonsillopharyngitis. After hospital admission, patient was treated with penicillin during the period of 10 days, antihypertensive medications (captopril, furosemide, including restricted diet of salt. After the treatment, patient became better. On demission it was found proteinuria and microhematuria PSGN is very serious disease, which leaves severe complications if the valid therapy with penicillin is not used in propriety time, during the recommended period of 10 days.

  12. Association between pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections disease and tumor necrosis factor-? gene?308 g/a, ?850 c/t polymorphisms in 4-12-year-old children in Adana/Turkey

    OpenAIRE

    Luleyap, H. Umit; Onatoglu, Dilge; Yilmaz, M. Bertan; Alptekin, Davut; Tahiroglu, Aysegul Y.; Cetiner, Salih; Pazarbasi, Ayfer; Unal, Ilker; Avci, Ayse; Comertpay, Gamze

    2013-01-01

    Objectives: Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) is a newly defined disease in neuropsychiatry and occurs with an autoimmune mechanism after Group A Beta Hemolytic Streptococcus (GABHS) infection. Tumor necrosis factor (TNF), encoded by TNF-α gene has an important role in the apoptotic mechanisms of autoimmune diseases. Recently, TNF-α polymorphisms and autoimmune/psychiatric disorders have been reported to be related. In this regar...

  13. Group A Streptococcal Infections

    Science.gov (United States)

    ... Relations Cyber Infrastructure Computational Biology Equal Employment Opportunity Ethics Global Research Office of Mission Integration and Financial Management Strategic Planning Workforce Effectiveness Workplace Solutions Technology Transfer Intellectual Property Division of AIDS ...

  14. Group B streptococcal metastatic endophthalmitis.

    Science.gov (United States)

    Nagelberg, H P; Petashnick, D E; To, K W; Woodcome, H A

    1994-04-15

    Reports of invasive Group B Streptococcus infection in adults with underlying medical conditions have been increasing. Ocular infection with this organism is unusual. Metastatic endophthalmitis in adults caused by this organism has been reported rarely and has only been associated with endocarditis. We encountered two cases of Group B streptococcal metastatic endophthalmitis in adults who did not have endocarditis. These cases reflect the increasing incidence of invasive Group B Streptococcus infection with its varying manifestations. Additionally, they emphasize the importance of considering this pathogen as a cause of metastatic endophthalmitis in adults with predisposing illnesses.

  15. Pulmonary Renal Syndrome After Streptococcal Pharyngitis

    Directory of Open Access Journals (Sweden)

    Gopi Mara-Koosham PhD

    2016-04-01

    Full Text Available Pulmonary renal syndrome is a class of small vessel vasculitides that are characterized by the dual presentation of diffuse alveolar hemorrhage (DAH and glomerulonephritis. Pulmonary renal syndrome has multiple etiologies, but its development has been rarely reported following infection with group A streptococcus. We present the case of a 36-year-old Native American male who was transferred to our facility due to refractory hypoxic respiratory failure. He had been diagnosed with streptococcal pharyngitis 2 weeks prior to admission. Given the presence of hemoptysis, bronchoscopy was performed and was consistent with DAH. Urinalysis demonstrated hematuria and proteinuria, in the setting of elevated creatinine and blood urea nitrogen. Additionally, antistreptolysin O titer was positive. Given the constellation of laboratory findings and history of streptococcal pharyngitis, the patient was diagnosed with PRS secondary to streptococcal infection. High-dose methylprednisolone was initiated with concomitant plasmapheresis. He was extubated successfully after his respiratory status improved and was eventually discharged home after making a full recovery within 2 weeks after admission. This case illustrates the importance of clinically relevant sequelae of streptococcal infection as well as the appropriate treatment of PRS secondary to streptococcal pharyngitis with plasmapheresis and intravenous corticosteroids.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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).

  1. 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.

  2. [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

  3. Neuronal antibody biomarkers for Sydenham's chorea identify a new group of children with chronic recurrent episodic acute exacerbations of tic and obsessive compulsive symptoms following a streptococcal infection.

    Science.gov (United States)

    Singer, Harvey S; Mascaro-Blanco, Adda; Alvarez, Kathy; Morris-Berry, Christina; Kawikova, Ivana; Ben-Pazi, Hilla; Thompson, Carol B; Ali, Syed F; Kaplan, Edward L; Cunningham, Madeleine W

    2015-01-01

    Several autoantibodies (anti-dopamine 1 (D1R) and 2 (D2R) receptors, anti-tubulin, anti-lysoganglioside-GM1) and antibody-mediated activation of calcium calmodulin dependent protein kinase II (CaMKII) signaling activity are elevated in children with Sydenham's chorea (SC). Recognizing proposed clinical and autoimmune similarities between SC and PANDAS (pediatric autoimmune neuropsychiatric disorder associated with a streptococcal infection), we sought to identify serial biomarker changes in a slightly different population. Antineuronal antibodies were measured in eight children (mean 11.3 years) with chronic, dramatic, recurrent tics and obsessive-compulsive disorder (OCD) associated with a group A β-hemolytic streptococcal (GABHS) respiratory tract infection, but differing because they lacked choreiform movements. Longitudinal serum samples in most subjects included two pre-exacerbation samples, Exac), one midst Exac (abrupt recurrence of tic/OCD; temporally association with a GABHS infection in six of eight subjects), and two post-Exac. Controls included four groups of unaffected children (n = 70; mean 10.8 years) obtained at four different institutions and published controls. Clinical exacerbations were not associated with a significant rise in antineuronal antibody titers. CaMKII activation was increased at the GABHS exacerbation point in 5/6 subjects, exceeded combined and published control's 95th percentile at least once in 7/8 subjects, and median values were elevated at each time point. Anti-tubulin and anti-D2R titers did not differ from published or combined control group's 95th percentile or median values. Differences in anti-lysoganglioside-GM1 and anti-D1R titers were dependent on the selected control. Variances in antibody titers and CaMKII activation were identified among the institutional control groups. Based on comparisons to published studies, results identify two groups of PANDAS: 1) a cohort, represented by this study, which lacks choreiform

  4. Neuronal antibody biomarkers for Sydenham's chorea identify a new group of children with chronic recurrent episodic acute exacerbations of tic and obsessive compulsive symptoms following a streptococcal infection.

    Directory of Open Access Journals (Sweden)

    Harvey S Singer

    Full Text Available Several autoantibodies (anti-dopamine 1 (D1R and 2 (D2R receptors, anti-tubulin, anti-lysoganglioside-GM1 and antibody-mediated activation of calcium calmodulin dependent protein kinase II (CaMKII signaling activity are elevated in children with Sydenham's chorea (SC. Recognizing proposed clinical and autoimmune similarities between SC and PANDAS (pediatric autoimmune neuropsychiatric disorder associated with a streptococcal infection, we sought to identify serial biomarker changes in a slightly different population. Antineuronal antibodies were measured in eight children (mean 11.3 years with chronic, dramatic, recurrent tics and obsessive-compulsive disorder (OCD associated with a group A β-hemolytic streptococcal (GABHS respiratory tract infection, but differing because they lacked choreiform movements. Longitudinal serum samples in most subjects included two pre-exacerbation samples, Exac, one midst Exac (abrupt recurrence of tic/OCD; temporally association with a GABHS infection in six of eight subjects, and two post-Exac. Controls included four groups of unaffected children (n = 70; mean 10.8 years obtained at four different institutions and published controls. Clinical exacerbations were not associated with a significant rise in antineuronal antibody titers. CaMKII activation was increased at the GABHS exacerbation point in 5/6 subjects, exceeded combined and published control's 95th percentile at least once in 7/8 subjects, and median values were elevated at each time point. Anti-tubulin and anti-D2R titers did not differ from published or combined control group's 95th percentile or median values. Differences in anti-lysoganglioside-GM1 and anti-D1R titers were dependent on the selected control. Variances in antibody titers and CaMKII activation were identified among the institutional control groups. Based on comparisons to published studies, results identify two groups of PANDAS: 1 a cohort, represented by this study, which lacks

  5. Management of group B streptococcal bacteriuria in pregnancy.

    Science.gov (United States)

    Allen, Victoria M; Yudin, Mark H

    2012-05-01

    To provide information regarding the management of group B streptococcal (GBS) bacteriuria to midwives, nurses, and physicians who are providing obstetrical care. The outcomes considered were neonatal GBS disease, preterm birth, pyelonephritis, chorioamnionitis, and recurrence of GBS colonization. Medline, PubMed, and the Cochrane database were searched for articles published in English to December 2010 on the topic of GBS bacteriuria in pregnancy. Bacteriuria is defined in this clinical practice guideline as the presence of bacteria in urine, regardless of the number of colony-forming units per mL (CFU/mL). Low colony counts refer to pregnancies in which it is appropriate to treat GBS bacteriuria to optimize maternal and perinatal outcomes, to reduce the occurrences of antibiotic anaphylaxis, and to prevent increases in antibiotic resistance to GBS and non-GBS pathogens. No cost-benefit analysis is provided. 1. Treatment of any bacteriuria with colony counts ≥ 100 000 CFU/mL in pregnancy is an accepted and recommended strategy and includes treatment with appropriate antibiotics. (II-2A) 2. Women with documented group B streptococcal bacteriuria (regardless of level of colony-forming units per mL) in the current pregnancy should be treated at the time of labour or rupture of membranes with appropriate intravenous antibiotics for the prevention of early-onset neonatal group B streptococcal disease. (II-2A) 3. Asymptomatic women with urinary group B streptococcal colony counts pregnancy should not be treated with antibiotics for the prevention of adverse maternal and perinatal outcomes such as pyelonephritis, chorioamnionitis, or preterm birth. (II-2E) 4. Women with documented group B streptococcal bacteriuria should not be re-screened by genital tract culture or urinary culture in the third trimester, as they are presumed to be group B streptococcal colonized. (II-2D).

  6. 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 ...

  7. 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.

  8. 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.

  9. Vitamin D Deficiency in Obsessive-Compulsive Disorder Patients with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections: A Case Control Study.

    Science.gov (United States)

    Çelik, Gonca; Taş, Didem; Tahiroğlu, Ayşegül; Avci, Ayşe; Yüksel, Bilgin; Çam, Perihan

    2016-03-01

    Previous studies have indicated that vitamin D deficiency is common in psychiatric patients, particularly in those with neuropsychiatric disorders such as autism and schizophrenia. Vitamin D is an important neurosteroid hormone and immunomodulatory agent that also has bone metabolic effects. There has been an increasing interest in immune-related neuropsychiatric symptoms that are triggered by group A beta-hemolytic streptococcal infections. In this study, we aimed to compare the serum levels of vitamin D between obsessive-compulsive disorder (OCD) patients with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) and control subjects. Thirty-three OCD patients with PANDAS and 20 healthy controls were enrolled in the study. Serum 25-hydroxyvitamin D (25-(OH) D), calcium, phosphorus, alkaline phosphatase, and parathormone levels of the two groups were compared. Serum 25-(OH) D levels of vitamin D deficiency. The children's Yale-Brown Obsessive Compulsive Scale (YBOCS) and Clinical Global Impression (CGI) were used to assess the severity of OCD symptoms. There was no significant difference in serum 25-(OH) D levels between the patient and control groups. However, vitamin D deficiency was significantly more frequent in the patient group than in the control group (48.5% vs. 20.0%; p=0.038). Moreover, OCD patients with vitamin D deficiency had higher rates of comorbid ADHD than those without vitamin D deficiency (87.5% vs. 52.6%; p=0.027). While serum phosphorus levels were negatively correlated with age as well as alkaline phosphatase and ASO levels, they were positively correlated with the YBOCS total score and global severity score. Serum parathormone levels were positively correlated with the YBOCS total score, compulsion score, obsession score, and global severity score. This study supports the hypothesis that an association between vitamin D metabolism and PANDAS-related OCD exists. We suggest that biochemical

  10. Gut Microbiota Profiling and Gut-Brain Crosstalk in Children Affected by Pediatric Acute-Onset Neuropsychiatric Syndrome and Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections.

    Science.gov (United States)

    Quagliariello, Andrea; Del Chierico, Federica; Russo, Alessandra; Reddel, Sofia; Conte, Giulia; Lopetuso, Loris R; Ianiro, Gianluca; Dallapiccola, Bruno; Cardona, Francesco; Gasbarrini, Antonio; Putignani, Lorenza

    2018-01-01

    Pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) are conditions that impair brain normal neurologic function, resulting in the sudden onset of tics, obsessive-compulsive disorder, and other behavioral symptoms. Recent studies have emphasized the crosstalk between gut and brain, highlighting how gut composition can influence behavior and brain functions. Thus, the present study investigates the relationship between PANS/PANDAS and gut microbiota ecology. The gut composition of a cohort of 30 patients with PANS/PANDAS was analyzed and compared to control subjects using 16S rRNA-based metagenomics. Data were analyzed for their α- and β-diversity; differences in bacterial distribution were detected by Wilcoxon and LEfSe tests, while metabolic profile was predicted via PICRUSt software. These analyses demonstrate the presence of an altered bacterial community structure in PANS/PANDAS patients with respect to controls. In particular, ecological analysis revealed the presence of two main clusters of subjects based on age range. Thus, to avoid age bias, data from patients and controls were split into two groups: 4-8 years old and >9 years old. The younger PANS/PANDAS group was characterized by a strong increase in Bacteroidetes; in particular, Bacteroides , Odoribacter , and Oscillospira were identified as potential microbial biomarkers of this composition type. Moreover, this group exhibited an increase of several pathways concerning the modulation of the antibody response to inflammation within the gut as well as a decrease in pathways involved in brain function (i.e., SCFA, D-alanine and tyrosine metabolism, and the dopamine pathway). The older group of patients displayed a less uniform bacterial profile, thus impairing the identification of distinct biomarkers. Finally, Pearson's analysis between bacteria and anti-streptolysin O titer reveled a

  11. 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

  12. 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.

  13. Beta-hemolytic Streptococcal Bacteremia

    DEFF Research Database (Denmark)

    Nielsen, Hans Ulrik; Kolmos, Hans Jørn; Frimodt-Møller, Niels

    2002-01-01

    Bacteremia with beta-hemolytic Streptococci groups A, B, C and G has a mortality rate of approximately 20%. In this study we analyzed the association of various patient risk factors with mortality. Records from 241 patients with beta-hemolytic streptococcal bacteremia were reviewed with particular...... attention to which predisposing factors were predictors of death. A logistic regression model found age, burns, immunosuppressive treatment and iatrogenic procedures prior to the infection to be significant predictors of death, with odds ratios of 1.7 (per decade), 19.7, 3.6 and 6.8, respectively...

  14. 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)

  15. 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

  16. 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.

  17. 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....

  18. [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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. [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

  7. 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.

  8. 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…

  9. 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

  10. 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

  11. 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 ...

  12. 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

  13. Choriodecidual group B streptococcal inoculation induces fetal lung injury without intra-amniotic infection and preterm labor in Macaca nemestrina.

    Directory of Open Access Journals (Sweden)

    Kristina M Adams Waldorf

    Full Text Available BACKGROUND: Early events leading to intrauterine infection and fetal lung injury remain poorly defined, but may hold the key to preventing neonatal and adult chronic lung disease. Our objective was to establish a nonhuman primate model of an early stage of chorioamnionitis in order to determine the time course and mechanisms of fetal lung injury in utero. METHODOLOGY/PRINCIPAL FINDINGS: Ten chronically catheterized pregnant monkeys (Macaca nemestrina at 118-125 days gestation (term=172 days received one of two treatments: 1 choriodecidual and intra-amniotic saline (n=5, or 2 choriodecidual inoculation of Group B Streptococcus (GBS 1×10(6 colony forming units (n=5. Cesarean section was performed regardless of labor 4 days after GBS or 7 days after saline infusion to collect fetal and placental tissues. Only two GBS animals developed early labor with no cervical change in the remaining animals. Despite uterine quiescence in most cases, blinded review found histopathological evidence of fetal lung injury in four GBS animals characterized by intra-alveolar neutrophils and interstitial thickening, which was absent in controls. Significant elevations of cytokines in amniotic fluid (TNF-α, IL-8, IL-1β, IL-6 and fetal plasma (IL-8 were detected in GBS animals and correlated with lung injury (p<0.05. Lung injury was not directly caused by GBS, because GBS was undetectable in amniotic fluid (~10 samples tested/animal, maternal and fetal blood by culture and polymerase chain reaction. In only two cases was GBS cultured from the inoculation site in low numbers. Chorioamnionitis occurred in two GBS animals with lung injury, but two others with lung injury had normal placental histology. CONCLUSIONS/SIGNIFICANCE: A transient choriodecidual infection can induce cytokine production, which is associated with fetal lung injury without overt infection of amniotic fluid, chorioamnionitis or preterm labor. Fetal lung injury may, thus, occur silently without

  14. Fatores de risco para o desenvolvimento de sepse neonatal precoce em hospital da rede pública do Brasil Risk factors for early-onset neonatal sepsis in Brazilian public hospital short-title: early-onset neonatal sepsis

    Directory of Open Access Journals (Sweden)

    Ana Paula Goulart

    2006-06-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: O conhecimento dos fatores de risco associados à sepse neonatal precoce em unidade de neonatologia, inserida na realidade de nosso sistema de saúde, no sentido de se detectar, prevenir e adotar medidas específicas e reduzir as taxas de mortalidade nessa faixa etária. O objetivo deste estudo foi determinar os fatores de risco associados a sepse neonatal precoce em hospital de referência em neonatologia ligado à rede pública de saúde. MÉTODO: Foi realizado um estudo observacional, prospectivo, tipo caso-controle. Foram incluídos os recém-nascidos com diagnóstico de sepse precoce e como controle, recém-nascidos sem infecção neonatal nascido na mesma data do recém-nascido considerado como caso. Foram incluídos 50 casos e três controles para cada caso, resultando em amostra total de 200 pacientes. Foi considerada estatisticamente significativa a associação quando p BACKGROUND AND OBJECTIVES: The determination of the risk factors to early-onset neonatal sepsis in our country is essential to prevent and reduce the mortality associated with this syndrome. Thus, the objective of this study was to determine the frequency and associated risk factors to early-onset neonatal sepsis in public hospital in Southern Brazil. METHODS: Observational, case-control study. Were included neonates with diagnostic of early-onset neonatal sepsis and as controls, neonates without neonatal infection. Were included 50 cases and 3 controls for each case resulting in a total sample of 200 patients. Associations were considered significant when p < 0.05. RESULTS: The sepsis frequency was 50.3 per 1000 born-alive. Risk factors associated to the development of neonatal sepsis were prematurity (OR 9.33; p < 0.001, low birth weight (OR 11.74; p < 0.001, maternal infection (OR 2.28; p = 0.009, mother with history of previous infant with neonatal sepsis (OR 6.43; p = 0.035 and rupture of the membranes more than 18 hours before delivery

  15. 链球菌感染及家庭因素与小儿抽动障碍的关系%Relationship of streptococcal infection and family factors with tic disorder among children

    Institute of Scientific and Technical Information of China (English)

    高翠琴

    2017-01-01

    目的 探讨小儿抽动障碍与链球菌感染、家庭因素的关系.方法 选取小儿抽动障碍患儿共60例为观察组、100例健康儿童作为对照组.检测并比较两组链球菌感染情况、血清抗DNA酶B和肿瘤坏死因子-α(TNF-α)水平,同时对两组进行相关家庭因素的问卷调查;采用logistic回归模型分析影响小儿抽动障碍发生的危险因素.结果 观察组链球菌感染率为41.67%,高于对照组的18.00%(P<0.05).观察组抗DNA酶B滴度、TNF-α水平均高于对照组(P<0.05).对照组存在打骂体罚、孕期营养不良、任性发脾气、注意力分散、压力大、近期有感染症状者的比例高于观察组(P<0.05).Logistic回归分析结果显示打骂体罚、孕期营养不良、高抗DNA酶B滴度、压力大和任性发脾气是小儿抽动障碍的独立危险因素(P<0.05).结论 抽动障碍与链球菌感染相关,而父母打骂、母亲孕期营养不良以及家庭环境和个性也是小儿抽动障碍发生的危险因素,在临床上应该高度重视.%Objective To explore the relationship of streptococcal infection and family factors with tic disorder among children.Methods Sixty children with tic disorder were enrolled as observation group and 100 healthy children as control group.The incidence of streptococcal infection,and the levels of serum anti-deoxyribonuclease B(ADNase B) and tumor necrosis factors-α(TNF-α) were determined and compared between the two groups.A questionnaire survey on relevant family factors was conducted in both groups.Multivariate logistic regression model was used to analyze the risk factors for the incidence of tic disorder in children.Results The streptococcal infection rate of the observation group was 41.67%,and was higher than that of the control group(18.00%;P<0.05).The titer of ADNase B and TNF-α level of the observation group were higher than those of the control group(P<0.05).The proportions of children with scold and corporal

  16. 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.

  17. 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.

  18. Mothers' experience of caring for a child with early onset scoliosis: A qualitative descriptive study.

    Science.gov (United States)

    Lauder, Bonnie; Sinclair, Peter M; Maguire, Jane

    2018-04-01

    This study aimed to identify and describe the experience of parents of children diagnosed with early onset scoliosis living in Australia. Chronic childhood disease has a major impact on health-related quality of life. Caring for a child with a chronic illness is well documented but the specific experiences of parents who care for children with early onset scoliosis, a rare but devastating illness, has not been explored. Numerous studies have described the interrelated psychological, financial, social, physical and logistical factors that impact the experience of the caregiver role with various diseases, but in the case of early onset scoliosis, limited studies have been conducted about the parental experience. A qualitative descriptive design was used. A snowball sampling technique assisted in the recruitment. Parents invited to the study included mothers, fathers and guardians. Data were collected through semistructured interviews and transcribed verbatim. Transcripts were analysed thematically. Data collection complied with the Consolidated criteria for reporting qualitative research guidelines. Twelve mothers of children with early onset scoliosis were interviewed, as only mothers consented to participate. Four major themes emerged: emotional rollercoaster ride, a lack of resources, money talks and pervasive burden. Factors that impacted on the participants' ability to confront, manage and endure caring for a child with early onset scoliosis emerged from the data. The findings suggest there are multiple factors that influence the experience of mothers' caring for a child with early onset scoliosis. The recognition and appropriate management of these factors by healthcare professionals have the potential to improve the quality of life of parents who care for a child with early onset scoliosis. Healthcare professionals have first-line contact with parents of children with early onset scoliosis and are well placed to provide parents with evidence-based education

  19. Differential Neurodevelopmental Trajectories in Patients With Early-Onset Bipolar and Schizophrenia Disorders

    Science.gov (United States)

    Arango, Celso

    2014-01-01

    Schizophrenia and bipolar disorders share not only clinical features but also some risk factors such as genetic markers and childhood adversity, while other risk factors such as urbanicity and obstetric complications seem to be specific to schizophrenia. An intriguing question is whether the well-established abnormal neurodevelopment present in many children and adolescents who eventually develop schizophrenia is also present in bipolar patients. The literature on adult bipolar patients is controversial. We report data on a subgroup of patients with pediatric-onset psychotic bipolar disorder who seem to share some developmental trajectories with patients with early-onset schizophrenia. These early-onset psychotic bipolar patients have low intelligence quotient, more neurological signs, reduced frontal gray matter at the time of their first psychotic episode, and greater brain changes than healthy controls in a pattern similar to early-onset schizophrenia cases. However, patients with early-onset schizophrenia seem to have more social impairment, developmental abnormalities (eg, language problems), and lower academic achievement in childhood than early-onset bipolar patients. We suggest that some of these abnormal developmental trajectories are more related to the phenotypic features (eg, early-onset psychotic symptoms) of these 2 syndromes than to categorically defined Diagnostic and Statistical Manual of Mental Disorders disorders. PMID:24371326

  20. 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.

  1. [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.

  2. Family history influences the early onset of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Chung-Hwa Park; Seung-Hee Jeong; Hyeon-Woo Yim; Jin Dong Kim; Si Hyun Bae; Jong Young Choi; Seung Kew Yoon

    2012-01-01

    AIM:To evaluate the relationship between a positive family history of primary liver cancer and hepatocellular carcinoma (HCC) development in Korean HCC patients.METHODS:We studied a total of 2242 patients diagnosed with HCC between January 1990 and July 2008,whose family history of primary liver cancer was clearly described in the medical records.RESULTS:Of the 2242 patients,165 (7.4%) had a positive family history of HCC and 2077 (92.6%) did not.The male to female ratio was 3.6:1,and the major causes of HCC were chronic hepatitis B virus (HBV) infection in 75.1%,chronic hepatitis C virus infection in 13.2% and alcohol in 3.1%.The median ages at diagnosis in the positive-and negative-history groups were 52 years (range:29-79 years) and 57 years (range:18-89 years),respectively (P < 0.0001).Furthermore,among 1713 HCC patients with HBV infection,the number of patients under 45 years of age out of 136 patients with positive family history was 26 (19.1%),whereas those out of 1577 patients with negative family history was 197 (12.5%),suggesting that a positive family history may be associated with earlier development of HCC in the Korean population (P =0.0028).CONCLUSION:More intensive surveillance maybe recommended to those with a positive family history of HCC for earlier diagnosis and proper management especially when HBV infection is present.

  3. A Prospective Study to Compare the Diagnostic Value of Serum Procalcitonin and Crp in Early Onset Sepsis

    Directory of Open Access Journals (Sweden)

    Suresh Kumar Verma

    2017-10-01

    Full Text Available Introduction: Neonatal sepsis is the most common cause of death in newborns in developing countries. Prompt diagnosis is the critical determinant in its outcome. As manifestations are often vague, clinically it is difficult to differentiate sepsis from non-infective conditions. Timely diagnosis is important as delay in initiation of antimicrobials can prove fatal. On the other hand empirical use of antibiotics not only increases the risk of antibiotic resistance but also delays the diagnosis of true condition. Procalcitonin (PCT has been well evaluated in late onset sepsis but data pertaining to Early Onset Sepsis (EOS are still lacking. We compared the diagnostic value of PCT and CRP (C-Reactive Protein in EOS. Aim: To compare the diagnostic value of serum PCT and CRP in early onset sepsis. Materials and Methods: It was a prospective observational study conducted in Neonatal Intensive Care Unit of the Department of Paediatrics, Dr.S.N. Medical College, Jodhpur, India. All neonates delivered in hospitals attached to this medical college or referred here within 7 days of life and having ≥2 perinatal risk factors for sepsis or displaying clinical sepsis were included in the study. All enrolled neonates were subjected to sepsis screen, PCT levels and blood culture at birth or admission which ever was the earliest. PCT levels ≥ 0.5 ng/ml and CRP levels above 8mg/l were considered positive for EOS. Results: Sensitivity and negative predictive value of PCT were higher than CRP (90.12% vs. 50.62% and 93.33% vs. 79.06% respectively. Also it had a higher positive predictive value of 40.56% than CRP where it was 37.61%. CRP was more specific (68.95% vs. 51.4% with overall higher diagnostic accuracy (0.64 vs. 0.61 in comparison to PCT. Conclusion: PCT is more sensitive and has a higher negative predictive value than CRP in early onset sepsis. Higher positive predictive value and specificity of CRP suggest that, PCT should not be used alone rather

  4. Systematic Search for Primary Immunodeficiency in Adults With Infections

    Science.gov (United States)

    2017-12-21

    Complement Deficiency; Antibody Deficiency; Chronic Sinus Infection; Meningitis, Bacterial; Pneumonia, Bacterial; Otitis Media; Streptococcal Infection; Neisseria Infections; Haemophilus Influenza; Pneumococcal Infections

  5. Controlled Human Infection for Vaccination Against Streptococcus Pyogenes

    Science.gov (United States)

    2018-04-26

    Streptococcus Pyogenes Pharyngitis; Streptococcus Pharyngitis; Strep Throat; Streptococcus Pyogenes Infection; Group A Streptococcus: B Hemolytic Pharyngitis; Group A Streptococcal Infection; Gram-Positive Bacterial Infections; Bacterial Infections

  6. Proteomics Mapping of Cord Blood Identifies Haptoglobin ?Switch-On? Pattern as Biomarker of Early-Onset Neonatal Sepsis in Preterm Newborns

    OpenAIRE

    Buhimschi, Catalin S.; Bhandari, Vineet; Dulay, Antonette T.; Nayeri, Unzila A.; Abdel-Razeq, Sonya S.; Pettker, Christian M.; Thung, Stephen; Zhao, Guomao; Han, Yiping W.; Bizzarro, Matthew; Buhimschi, Irina A.

    2011-01-01

    Background Intra-amniotic infection and/or inflammation (IAI) are important causes of preterm birth and early-onset neonatal sepsis (EONS). A prompt and accurate diagnosis of EONS is critical for improved neonatal outcomes. We sought to explore the cord blood proteome and identify biomarkers and functional protein networks characterizing EONS in preterm newborns. Methodology/Principal Findings We studied a prospective cohort of 180 premature newborns delivered May 2004-September 2009. A prote...

  7. 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.

  8. 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.

  9. 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.

  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. Exercise and Early-Onset Alzheimer’s Disease: Theoretical Considerations

    Directory of Open Access Journals (Sweden)

    Astrid M. Hooghiemstra

    2012-04-01

    Full Text Available Background/Aims: Although studies show a negative relationship between physical activity and the risk for cognitive impairment and late-onset Alzheimer’s disease, studies concerning early-onset Alzheimer’s disease (EOAD are lacking. This review aims to justify the value of exercise interventions in EOAD by providing theoretical considerations that include neurobiological processes. Methods: A literature search on key words related to early-onset dementia, exercise, imaging, neurobiological mechanisms, and cognitive reserve was performed. Results/Conclusion: Brain regions and neurobiological processes contributing to the positive effects of exercise are affected in EOAD and, thus, provide theoretical support for exercise interventions in EOAD. Finally, we present the design of a randomized controlled trial currently being conducted in early-onset dementia patients.

  12. 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...

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

    Directory of Open Access Journals (Sweden)

    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

  14. 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.

  15. 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.

  16. Streptococcal tonsillopharyngitis – principles ofdiagnosis and treatment

    Directory of Open Access Journals (Sweden)

    Marcin Dziekiewicz

    2016-06-01

    Full Text Available Tonsillopharyngitis is one of the main causes of medical appointments. In fact, a seemingly simple diagnosis and treatment causes various problems and is the reason of many problems and errors, including antibiotic misuse or overuse. The most frequent aetiological agents of pharyngitis relate to viruses. A carefully taken medical history and physical examination can help distinguish patients in whom bacterial (streptococcal aetiology should be suspected. However, signs and symptoms themselves do not usually allow the correct diagnosis to be established. A clinical suspicion of bacterial infection must be confirmed microbiologically. The best practice is a throat culture. Rapid tests for the presence of Streptococcus pyogenes antigen are a convenient alternative. They are characterised by high sensitivity and specificity. The  first-line treatment in streptococcal tonsillopharyngitis is phenoxymethylpenicillin used for 10 days. Streptococcus pyogenes is uniformly sensitive to this antibiotic. Cefadroxil is reserved for patients with non-immediate hypersensitivity to penicillin and Streptococcus pyogenes carriers. Macrolides, in turn, should be used only if immediate hypersensitivity occurs. In this case, 3–5-day treatment with azithromycin is a convenient alternative to clarithromycin. It is important to use its high, double doses – the standard dose is ineffective. Treatment of streptococcal tonsillopharyngitis with amoxicillin, amoxicillin with clavulanic acid and cefuroxime axetil is considered inappropriate and harmful. These are relatively broad-spectrum antibiotics, but their overuse is conductive to the spread of pneumococci of reduced penicillin sensitivity.

  17. 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

  18. 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

  19. The role of SLC2A1 in early onset and childhood absence epilepsies

    DEFF Research Database (Denmark)

    Muhle, Hiltrud; Helbig, Ingo; Frøslev, Tobias Guldberg

    2013-01-01

    Early Onset Absence Epilepsy constitutes an Idiopathic Generalized Epilepsy with absences starting before the age of four years. Mutations in SLC2A1, encoding the glucose transporter, account for approximately 10% of EOAE cases. The role of SLC2A1 mutations in absence epilepsies with a later onset...

  20. 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

  1. 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...

  2. 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

  3. 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

  4. Estrogen use and early onset Alzheimer's disease: a population-based study

    NARCIS (Netherlands)

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

    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

  5. 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…

  6. 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 ...

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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),…

  15. 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.

  16. 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...

  17. 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

  18. 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.

  19. 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…

  20. 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

  1. 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

  2. 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

  3. 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…

  4. 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

  5. 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.

  6. Novel loss-of-function variants in DIAPH1 associated with syndromic microcephaly, blindness, and early onset seizures.

    Science.gov (United States)

    Al-Maawali, Almundher; Barry, Brenda J; Rajab, Anna; El-Quessny, Malak; Seman, Ann; Coury, Stephanie Newton; Barkovich, A James; Yang, Edward; Walsh, Christopher A; Mochida, Ganeshwaran H; Stoler, Joan M

    2016-02-01

    Exome sequencing identified homozygous loss-of-function variants in DIAPH1 (c.2769delT; p.F923fs and c.3145C>T; p.R1049X) in four affected individuals from two unrelated consanguineous families. The affected individuals in our report were diagnosed with postnatal microcephaly, early-onset epilepsy, severe vision impairment, and pulmonary symptoms including bronchiectasis and recurrent respiratory infections. A heterozygous DIAPH1 mutation was originally reported in one family with autosomal dominant deafness. Recently, however, a homozygous nonsense DIAPH1 mutation (c.2332C4T; p.Q778X) was reported in five siblings in a single family affected by microcephaly, blindness, early onset seizures, developmental delay, and bronchiectasis. The role of DIAPH1 was supported using parametric linkage analysis, RNA and protein studies in their patients' cell lines and further studies in human neural progenitors cells and a diap1 knockout mouse. In this report, the proband was initially brought to medical attention for profound metopic synostosis. Additional concerns arose when his head circumference did not increase after surgical release at 5 months of age and he was diagnosed with microcephaly and epilepsy at 6 months of age. Clinical exome analysis identified a homozygous DIAPH1 mutation. Another homozygous DIAPH1 mutation was identified in the research exome analysis of a second family with three siblings presenting with a similar phenotype. Importantly, no hearing impairment is reported in the homozygous affected individuals or in the heterozygous carrier parents in any of the families demonstrating the autosomal recessive microcephaly phenotype. These additional families provide further evidence of the likely causal relationship between DIAPH1 mutations and a neurodevelopmental disorder. © 2016 Wiley Periodicals, Inc.

  7. First report of real-time monitoring of coagulation function potential and IgG subtype of anti-FVIII autoantibodies in a child with acquired hemophilia A associated with streptococcal infection and amoxicillin.

    Science.gov (United States)

    Takeyama, Masahiro; Nogami, Keiji; Kajimoto, Takahiro; Ogiwara, Kenichi; Matsumoto, Tomoko; Shima, Midori

    2018-01-01

    We describe an 8-year-old boy with acquired hemophilia A (AHA) associated with streptococcal infection and amoxicillin. Laboratory data revealed low factor VIII activity (FVIII:C, 1.5 IU/dl), and FVIII inhibitor (15.9 BU/ml). Comprehensive coagulation function assays, including rotation thromboelastometry (ROTEM ® ), revealed a markedly prolonged clotting time. Thrombin and plasmin generation (TG/PG) appeared to be moderately impaired. The inhibitor epitope of his anti-FVIII autoantibody recognized light and heavy chains. He was treated with Novoseven ® and prednisolone, resulting in rapid improvement. ROTEM showed the return of coagulation time to normal level on day 20, and TG gradually improved. PG was moderately reduced in the clinical early phase, but improved at day 20. The patient's IgG subtype was IgG 4 at onset. IgG 1 was transiently positive on day 20, but negative on day 46. FVIII inhibitor gradually decreased and was completely absent after day 46, along with the elevated FVIII:C. IgG4 was again elevated on day 83, followed by a rapid decrease, indicative of the presence of non-neutralizing antibody, which remains currently undetected. We for the first time report changes in comprehensive coagulation function and IgG subtype of anti-FVIII antibody in a rare pediatric case of AHA.

  8. 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.

  9. 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...

  10. Randomised, double-blind, placebo-controlled studies on flurbiprofen 8.75 mg lozenges in patients with/without group A or C streptococcal throat infection, with an assessment of clinicians' prediction of 'strep throat'.

    Science.gov (United States)

    Shephard, A; Smith, G; Aspley, S; Schachtel, B P

    2015-01-01

    Diagnosing group A streptococcus (Strep A) throat infection by clinical examination is difficult, and misdiagnosis may lead to inappropriate antibiotic use. Most patients with sore throat seek symptom relief rather than antibiotics, therefore, therapies that relieve symptoms should be recommended to patients. We report two clinical trials on the efficacy and safety of flurbiprofen 8.75 mg lozenge in patients with and without streptococcal sore throat. The studies enrolled adults with moderate-to-severe throat symptoms (sore throat pain, difficulty swallowing and swollen throat) and a diagnosis of pharyngitis. The practitioner assessed the likelihood of Strep A infection based on historical and clinical findings. Patients were randomised to flurbiprofen 8.75 mg or placebo lozenges under double-blind conditions and reported the three throat symptoms at baseline and at regular intervals over 24 h. A total of 402 patients received study medication (n = 203 flurbiprofen, n = 199 placebo). Throat culture identified Strep A in 10.0% of patients and group C streptococcus (Strep C) in a further 14.0%. The practitioners' assessments correctly diagnosed Strep A in 11/40 cases (sensitivity 27.5%, and specificity 79.7%). A single flurbiprofen lozenge provided significantly greater relief than placebo for all three throat symptoms, lasting 3-4 h for patients with and without Strep A/C. Multiple doses of flurbiprofen lozenges over 24 h also led to symptom relief, although not statistically significant in the Strep A/C group. There were no serious adverse events. The results highlight the challenge of identifying Strep A based on clinical features. With the growing problem of antibiotic resistance, non-antibiotic treatments should be considered. As demonstrated here, flurbiprofen 8.75 mg lozenges are an effective therapeutic option, providing immediate and long-lasting symptom relief in patients with and without Strep A/C infection. © 2014 John Wiley & Sons Ltd.

  11. [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

  12. 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...

  13. Risk of early-onset prostate cancer associated with occupation in the Nordic countries

    DEFF Research Database (Denmark)

    Hughes Barry, Kathryn; Martinsen, Jan Ivar; Alavanja, Michael C. R.

    2017-01-01

    -49 and those aged 50 or older. We also conducted separate analyses by period of follow-up, 1961-1985 and 1986-2005, corresponding to pre- and post-prostate-specific antigen (PSA) screening. RESULTS: For early-onset prostate cancer (n = 1521), we observed the highest SIRs for public safety workers (e......BACKGROUND: Early-onset prostate cancer is often more aggressive and may have a different aetiology than later-onset prostate cancer, but has been relatively little studied to date. We evaluated occupation in relation to early- and later-onset prostate cancer in a large pooled study. METHODS: We...... used occupational information from census data in five Nordic countries from 1960 to 1990. We identified prostate cancer cases diagnosed from 1961 to 2005 by linkage of census information to national cancer registries and calculated standardised incidence ratios (SIRs) separately for men aged 30...

  14. 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...

  15. 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)

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. The impact of initiation: Early onset marijuana smokers demonstrate altered Stroop performance and brain activation

    Directory of Open Access Journals (Sweden)

    K.A. Sagar

    2015-12-01

    Full Text Available Marijuana (MJ use is on the rise, particularly among teens and emerging adults. This poses serious public health concern, given the potential deleterious effects of MJ on the developing brain. We examined 50 chronic MJ smokers divided into early onset (regular MJ use prior to age 16; n = 24 and late onset (age 16 or later; n = 26, and 34 healthy control participants (HCs. All completed a modified Stroop Color Word Test during fMRI. Results demonstrated that MJ smokers exhibited significantly poorer performance on the Interference subtest of the Stroop, as well as altered patterns of activation in the cingulate cortex relative to HCs. Further, early onset MJ smokers exhibited significantly poorer performance relative to both HCs and late onset smokers. Additionally, earlier age of MJ onset as well as increased frequency and magnitude (grams/week of MJ use were predictive of poorer Stroop performance. fMRI results revealed that while late onset smokers demonstrated a more similar pattern of activation to the control group, a different pattern was evident in the early onset group. These findings underscore the importance of assessing age of onset and patterns of MJ use and support the need for widespread education and intervention efforts among youth.

  2. 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.

  3. Guttate Psoriasis Following Streptococcal Vulvovaginitis in a Five-year-old Girl.

    Science.gov (United States)

    Hernandez, Melia; Simms-Cendan, Judith; Zendell, Kathleen

    2015-10-01

    Guttate psoriasis is frequently associated with a preceding pharyngeal or perianal streptococcal infection in children. Despite Group A beta-hemolytic streptococci (GABHS) being the most common cause of specific bacterial vulvovaginitis in prepubertal girls, there are no reports of streptococcal vulvovaginitis triggering guttate psoriasis. A five-year-old girl presented with guttate psoriasis following an episode of Streptococcal pyogenes vulvovaginitis. Following antibiotic treatment and bacterial eradication she developed vulvar psoriasis that resolved with high potency topical steroids. Identification of an antecedent streptoccocal infection can help predict the long term prognosis in children with guttate psoriasis. The vulvovaginal area should be considered as a source of GABHS infection in young girls with guttate psoriasis, and cultures should be considered if symptoms are present. Published by Elsevier Inc.

  4. [Streptococcal mediastinitis after thyroidectomy. A literature review].

    Science.gov (United States)

    Bures, C; Zielinski, V; Klatte, T; Swietek, N; Kober, F; Tatzgern, E; Bobak-Wieser, R; Gschwandtner, E; Gilhofer, M; Wechsler-Fördös, A; Hermann, M

    2015-12-01

    Surgical site infections after thyroid surgery are mostly superficial and can be well treated. Streptococcal mediastinitis in contrast is a rare but life-threatening complication. A 57-year-old female patient experienced septic fever, increase of inflammation parameters and erythema 2 days after thyroid surgery for Graves' disease. This process was triggered by a three-compartment infection by group A Streptococcus (GAS) with involvement of the mediastinum. Therapy over 6 weeks including seven wound revisions with the patient under general anesthesia, pathogen-adapted antibiotic treatment and cervical negative pressure treatment managed to control the infection. A total of 21 cases have been published on this phenomenon, 11 of which had a fatal outcome. High fever and surgical site erythema in the early postoperative period after thyroid surgery can be signs of a GAS infection, which might lead to necrotizing, descending, life-threatening mediastinitis. Early diagnosis with support of computed tomography (CT) scans, immediate therapy including wound opening, lavage, intravenous antibiotic treatment with penicillin and clindamycin are vital. If treatment resistance occurs, cervical negative pressure treatment should be considered.

  5. 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

  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. 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.

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

    Science.gov (United States)

    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.

  9. 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

  10. 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.

  11. The Not-So-Good Prognosis of Streptococcal Periprosthetic Joint Infection Managed by Implant Retention : The Results of a Large Multicenter Study

    NARCIS (Netherlands)

    Lora-Tamayo, Jaime; Senneville, Éric; Ribera, Alba; Bernard, Louis; Dupon, Michel; Zeller, Valérie; Li, Ho Kwong; Arvieux, Cédric; Clauss, Martin; Uçkay, Ilker; Vigante, Dace; Ferry, Tristan; Iribarren, José Antonio; Peel, Trisha N; Sendi, Parham; Miksic, Nina Gorišek; Rodríguez-Pardo, Dolors; Del Toro, María Dolores; Fernández-Sampedro, Marta; Dapunt, Ulrike; Huotari, Kaisa; Davis, Joshua S; Palomino, Julián; Neut, Danielle; Clark, Benjamin M; Gottlieb, Thomas; Trebše, Rihard; Soriano, Alex; Bahamonde, Alberto; Guío, Laura; Rico, Alicia; Salles, Mauro J C; Pais, M José G; Benito, Natividad; Riera, Melchor; Gómez, Lucía; Aboltins, Craig A; Esteban, Jaime; Horcajada, Juan Pablo; O'Connell, Karina; Ferrari, Matteo; Skaliczki, Gábor; Juan, Rafael San; Cobo, Javier; Sánchez-Somolinos, Mar; Ramos, Antonio; Giannitsioti, Efthymia; Jover-Sáenz, Alfredo; Baraia-Etxaburu, Josu Mirena; Barbero, José María

    2017-01-01

    Background.: Streptococci are not an infrequent cause of periprosthetic joint infection (PJI). Management by debridement, antibiotics, and implant retention (DAIR) is thought to produce a good prognosis, but little is known about the real likelihood of success. Methods.: A retrospective,

  12. 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...

  13. 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

  14. 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...

  15. 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

  16. 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...

  17. [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.

  18. Early Diagnosis and Hematopoietic Stem Cell Transplantation for IL10R Deficiency Leading to Very Early-Onset Inflammatory Bowel Disease Are Essential in Familial Cases

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    Neslihan Edeer Karaca

    2016-01-01

    Full Text Available Alterations of immune homeostasis in the gut may result in development of inflammatory bowel disease. A five-month-old girl was referred for recurrent respiratory and genitourinary tract infections, sepsis in neonatal period, chronic diarrhea, perianal abscess, rectovaginal fistula, and hyperemic skin lesions. She was born to second-degree consanguineous, healthy parents. Her elder siblings were lost at 4 months of age due to sepsis and 1 year of age due to inflammatory bowel disease, respectively. Absolute neutrophil and lymphocyte counts, immunoglobulin levels, and lymphocyte subsets were normal ruling out severe congenital neutropenia and classic severe combined immunodeficiencies. Quantitative determination of oxidative burst was normal, excluding chronic granulomatous disease. Colonoscopy revealed granulation, ulceration, and pseudopolyps, compatible with colitis. Very early-onset colitis and perianal disease leading to fistula formation suggested probability of inherited deficiencies of IL-10 or IL-10 receptor. A mutation at position c.G477A in exon of the IL10RB gene, resulting in a stop codon at position p.W159X, was identified. The patient underwent myeloablative hematopoietic stem cell transplantation from full matched father at 11 months of age. Perianal lesions, chronic diarrhea, and recurrent infections resolved after transplantation. IL-10/IL-10R deficiencies must be considered in patients with early-onset enterocolitis.

  19. Early Onset Prosthetic Joint Infection and Bacteremia due to Campylobacter fetus Subspecies fetus

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    Igor Dumic

    2017-01-01

    Full Text Available Campylobacter fetus is a zoonotic pathogen that occasionally causes serious, relapsing, invasive disease, especially in immunocompromised hosts. We report a case of relapsing C. fetus diarrheal illness in a 75-year-old woman which resulted in secondary bacteremia and seeding of the left knee prosthetic joint. Patient responded favorably to debridement and retention of prosthesis in addition to six weeks of meropenem followed by chronic oral doxycycline suppressive therapy.

  20. Regulatory Role of GSK-3β on NF-κB, Nitric Oxide, and TNF-α in Group A Streptococcal Infection

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    Yu-Tzu Chang

    2013-01-01

    Full Text Available Group A streptococcus (GAS imposes a great burden on humans. Efforts to minimize the associated morbidity and mortality represent a critical issue. Glycogen synthase kinase-3β (GSK-3β is known to regulate inflammatory response in infectious diseases. However, the regulation of GSK-3β in GAS infection is still unknown. The present study investigates the interaction between GSK-3β, NF-κB, and possible related inflammatory mediators in vitro and in a mouse model. The results revealed that GAS could activate NF-κB, followed by an increased expression of inducible nitric oxide synthase (iNOS and NO production in a murine macrophage cell line. Activation of GSK-3β occurred after GAS infection, and inhibition of GSK-3β reduced iNOS expression and NO production. Furthermore, GSK-3β inhibitors reduced NF-κB activation and subsequent TNF-α production, which indicates that GSK-3β acts upstream of NF-κB in GAS-infected macrophages. Similar to the in vitro findings, administration of GSK-3β inhibitor in an air pouch GAS infection mouse model significantly reduced the level of serum TNF-α and improved the survival rate. The inhibition of GSK-3β to moderate the inflammatory effect might be an alternative therapeutic strategy against GAS infection.

  1. Outbreak of late-onset group B streptococcal infections in healthy newborn infants after discharge from a maternity hospital: a case report.

    Science.gov (United States)

    Kim, Hyung Jin; Kim, Soo Young; Seo, Won Hee; Choi, Byung Min; Yoo, Young; Lee, Kee Hyoung; Eun, Baik Lin; Kim, Hai Joong

    2006-04-01

    During a four-week period, four healthy term newborn infants born at a regional maternity hospital in Korea developed late-onset neonatal group B Streptococcus (GBS) infections, after being discharged from the same nursery. More than 10 days after their discharge, all of the infants developed fever, lethargy, and poor feeding behavior, and were subsequently admitted to the Korea University Medical Center, Ansan Hospital. GBS was isolated from the blood cultures of three babies; furthermore, GBS was isolated from 2 cerebral spinal fluid cultures. Three babies had meningitis, and GBS was isolated from their cerebral spinal fluid cultures. This outbreak was believed to reflect delayed infection after early colonization, originating from nosocomial sources within the hospital environment. This report underlines the necessity for Korean obstetricians and pediatricians to be aware of the risk of nosocomial transmissions of GBS infection in the delivery room and/or the nursery.

  2. 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.

  3. 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.

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

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    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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. 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.

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

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    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. 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.

  15. Genome-wide discovery of novel M1T1 group A streptococcal determinants important for fitness and virulence during soft-tissue infection.

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    Yoann Le Breton

    2017-08-01

    Full Text Available The Group A Streptococcus remains a significant human pathogen causing a wide array of disease ranging from self-limiting to life-threatening invasive infections. Epithelium (skin or throat colonization with progression to the subepithelial tissues is the common step in all GAS infections. Here, we used transposon-sequencing (Tn-seq to define the GAS 5448 genetic requirements for in vivo fitness in subepithelial tissue. A near-saturation transposon library of the M1T1 GAS 5448 strain was injected subcutaneously into mice, producing suppurative inflammation at 24 h that progressed to prominent abscesses with tissue necrosis at 48 h. The library composition was monitored en masse by Tn-seq and ratios of mutant abundance comparing the output (12, 24 and 48 h versus input (T0 mutant pools were calculated for each gene. We identified a total of 273 subcutaneous fitness (scf genes with 147 genes (55 of unknown function critical for the M1T1 GAS 5448 fitness in vivo; and 126 genes (53 of unknown function potentially linked to in vivo fitness advantage. Selected scf genes were validated in competitive subcutaneous infection with parental 5448. Two uncharacterized genes, scfA and scfB, encoding putative membrane-associated proteins and conserved among Gram-positive pathogens, were further characterized. Defined scfAB mutants in GAS were outcompeted by wild type 5448 in vivo, attenuated for lesion formation in the soft tissue infection model and dissemination to the bloodstream. We hypothesize that scfAB play an integral role in enhancing adaptation and fitness of GAS during localized skin infection, and potentially in propagation to other deeper host environments.

  16. Group B streptococcal infection of the choriodecidua induces dysfunction of the cytokeratin network in amniotic epithelium: a pathway to membrane weakening.

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    Jeroen P Vanderhoeven

    2014-03-01

    Full Text Available Early events leading to intrauterine infection remain poorly defined, but may hold the key to preventing preterm delivery. To determine molecular pathways within fetal membranes (chorioamnion associated with early choriodecidual infection that may progress to preterm premature rupture of membranes (PPROM, we examined the effects of a Group B Streptococcus (GBS choriodecidual infection on chorioamnion in a nonhuman primate model. Ten chronically catheterized pregnant monkeys (Macaca nemestrina at 118-125 days gestation (term = 172 days received choriodecidual inoculation of either GBS (n = 5 or saline (n = 5. Cesarean section was performed in the first week after GBS or saline inoculation. RNA extracted from chorioamnion (inoculation site was profiled by microarray. Single gene, Gene Set, and Ingenuity Pathway Analysis results were validated using qRT-PCR (chorioamnion, Luminex (amniotic fluid, AF, immunohistochemistry, and transmission electron microscopy (TEM. Despite uterine quiescence in most cases, significant elevations of AF cytokines (TNF-α, IL-8, IL-1β, IL-6 were detected in GBS versus controls (p2-fold change, p<0.05. Remarkably, GBS exposure was associated with significantly downregulated expression of multiple cytokeratin (CK and other cytoskeletal genes critical for maintenance of tissue tensile strength. Immunofluorescence revealed highly significant changes in the CK network within amniocytes with dense CK aggregates and retraction from the cell periphery (all p = 0.006. In human pregnancies affected by PPROM, there was further evidence of CK network retraction with significantly shorter amniocyte foot processes (p = 0.002. These results suggest early choriodecidual infection results in decreased cellular membrane integrity and tensile strength via dysfunction of CK networks. Downregulation of CK expression and perturbations in the amniotic epithelial cell intermediate filament network occur after GBS

  17. Genome-wide discovery of novel M1T1 group A streptococcal determinants important for fitness and virulence during soft-tissue infection.

    Science.gov (United States)

    Le Breton, Yoann; Belew, Ashton T; Freiberg, Jeffrey A; Sundar, Ganesh S; Islam, Emrul; Lieberman, Joshua; Shirtliff, Mark E; Tettelin, Hervé; El-Sayed, Najib M; McIver, Kevin S

    2017-08-01

    The Group A Streptococcus remains a significant human pathogen causing a wide array of disease ranging from self-limiting to life-threatening invasive infections. Epithelium (skin or throat) colonization with progression to the subepithelial tissues is the common step in all GAS infections. Here, we used transposon-sequencing (Tn-seq) to define the GAS 5448 genetic requirements for in vivo fitness in subepithelial tissue. A near-saturation transposon library of the M1T1 GAS 5448 strain was injected subcutaneously into mice, producing suppurative inflammation at 24 h that progressed to prominent abscesses with tissue necrosis at 48 h. The library composition was monitored en masse by Tn-seq and ratios of mutant abundance comparing the output (12, 24 and 48 h) versus input (T0) mutant pools were calculated for each gene. We identified a total of 273 subcutaneous fitness (scf) genes with 147 genes (55 of unknown function) critical for the M1T1 GAS 5448 fitness in vivo; and 126 genes (53 of unknown function) potentially linked to in vivo fitness advantage. Selected scf genes were validated in competitive subcutaneous infection with parental 5448. Two uncharacterized genes, scfA and scfB, encoding putative membrane-associated proteins and conserved among Gram-positive pathogens, were further characterized. Defined scfAB mutants in GAS were outcompeted by wild type 5448 in vivo, attenuated for lesion formation in the soft tissue infection model and dissemination to the bloodstream. We hypothesize that scfAB play an integral role in enhancing adaptation and fitness of GAS during localized skin infection, and potentially in propagation to other deeper host environments.

  18. A case of rheumatic fever with acute post-streptococcal glomerulonephritis and nephrotic syndrome caused by a cutaneous infection with beta-hemolytic streptococci

    Directory of Open Access Journals (Sweden)

    Carsten Sauer Mikkelsen

    2010-01-01

    Full Text Available A middle-aged patient of Greenlandic origin was referred for skin infection of the leg. An initial minor trauma of the skin of the distal right lower extremity was complicated by bullous erysipelas which cultured positive for group A β-hemolytic streptococci (GABHS. The clinical condition deteriorated and necrotizing fasciitis developed despite relevant surgical and antibiotic treatment. Approximately 3 weeks later, the patient developed arthralgia, impaired renal function with azotemia, hypertension and severe nephrotic syndrome with periorbital and peripheral edema. A kidney biopsy demonstrated endocapillary glomerulonephritis. Concomitantly, carditis with chest pain, moderately reduced left ventricular ejection fraction and mitral regurgitation were noted. The patient had no signs of pharyngitis in the whole period. The patient thus contracted poststreptococ glomerulonephritis and furthermore she fulfilled the criteria of acute rheumatic fever following a GABHS skin infection. We suggest a possible relation between a virulent GABHS clone causing NF and ARF.

  19. Acute Rheumatic Fever versus Post-Streptococcal Reactive Arthritis

    International Nuclear Information System (INIS)

    Ashry, K.M.

    2009-01-01

    Rheumatic fever is an inflammatory disease that may develop after a Group A streptococcal infection and can involve the heart, joints, skin, and brain. A migrating polyarthritis after throat infection with group A β-haemolytic streptococci is classically attributed to acute rheumatic fever (ARF). Sterile non-migratory arthritis may occur as a separate entity, the so called post streptococcal reactive arthritis (PSRA). This study aimed to identify clinical and serological differences of patients with reactive arthritis after infection with Lance field group Aβ-haemolytic streptococci, compared with acute rheumatic fever. Hundred and twenty patients were recruited for the study , they were classified into two groups according to the diagnosis of ARF and PSRA patients consecutively seen in the Rheumatology and the Pediatric wards. Clinical and laboratory data were assessed through a questionnaire. The diagnosis of rheumatic fever was made based on revised modified Jones' criteria, while the diagnosis of post streptococcal reactive arthritis was made based on Deighton criteria; these associated with laboratory data, electrocardiography, chest X-ray, and bi-dimensional echocardiography. Results revealed no significant differences between both groups as regard age where ρ>0.05, while there were a significant difference regarding the date of antecedent upper respiratory tract infection (ρ 0.05). Regarding the cardio logical changes P-R interval by ECG was prolonged in 19 patients (31.67%)and Echo study showed changes in 12 patient (20%) of cases of ARF patient only. On the basis of simple laboratory variables and management, it ws possible to differentiate ARF from PSRA patients. So it could be concluded that these two conditions are actually distinct identities

  20. Outbreak of Late-onset Group B Streptococcal Infections in Healthy Newborn Infants after Discharge from a Maternity Hospital: A Case Report

    OpenAIRE

    Kim, Hyung Jin; Kim, Soo Young; Seo, Won Hee; Choi, Byung Min; Yoo, Young; Lee, Kee Hyoung; Eun, Baik Lin; Kim, Hai Joong

    2006-01-01

    During a four-week period, four healthy term newborn infants born at a regional maternity hospital in Korea developed late-onset neonatal group B Streptococcus (GBS) infections, after being discharged from the same nursery. More than 10 days after their discharge, all of the infants developed fever, lethargy, and poor feeding behavior, and were subsequently admitted to the Korea University Medical Center, Ansan Hospital. GBS was isolated from the blood cultures of three babies; furthermore, G...

  1. Culture-proven early-onset neonatal sepsis in Arab states in the Gulf region: two-year prospective study.

    Science.gov (United States)

    Hammoud, Majeda S; Al-Taiar, Abdullah; Al-Abdi, Sameer Y; Bozaid, Hussain; Khan, Anwar; AlMuhairi, Laila M; Rehman, Moghis Ur

    2017-02-01

    To investigate the incidence and the pattern of causative organisms of culture-proven early-onset sepsis (EOS) in Arab states in the Gulf region. Five neonatal care units participated in this 2-year prospective study in Kuwait, the United Arab Emirates, and Saudi Arabia. Data were collected prospectively using a standardized data collection form. EOS was defined as the growth of a single potentially pathogenic organism from blood or cerebrospinal fluid in infants within 72h of birth, with clinical and laboratory findings consistent with infection. Out of 67 474 live births, 102 cases of EOS occurred. The overall incidence of EOS was 1.5 (95% confidence interval 1.2-1.8) per 1000 live-births, ranging from 2.64 per 1000 live-births in Kuwait to 0.40 per 1000 live-births in King Abdulaziz Hospital in Saudi Arabia. The most common causative organism of EOS was group B Streptococcus (GBS; 60.0%), followed by Escherichia coli (13%). The incidence of invasive GBS disease was 0.90 per 1000 live-births overall and ranged from 1.4 per 1000 live-births in Kuwait to 0.6 per 1000 live-births in Dubai Hospital. The incidence of EOS and the patterns of the causative organisms in the Arab states in the Gulf region are similar to those in developed countries before the era of intrapartum antibiotic prophylaxis. Efforts should be made to improve intrapartum antibiotic prophylaxis in the Arab state setting, which could avert large numbers of GBS infections. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. 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

  3. Successful Treatment of Necrotizing Fasciitis and Streptococcal Toxic Shock Syndrome with the Addition of Linezolid

    Directory of Open Access Journals (Sweden)

    Hana Rac

    2017-01-01

    Full Text Available Necrotizing fasciitis is a deep-seated subcutaneous tissue infection that is commonly associated with streptococcal toxic shock syndrome (TSS. Surgical debridement plus penicillin and clindamycin are the current standard of care. We report a case of necrotizing fasciitis and streptococcal TSS where linezolid was added after a failure to improve with standard therapy. Briefly after isolation of Streptococcus pyogenes from tissue cultures, the patient underwent two surgical debridement procedures and was changed to standard of care therapy. While the patient was hemodynamically stable, the patient’s wounds, leukocytosis, and thrombocytopenia all progressively worsened. After initiation of linezolid, the patient slowly improved clinically. The present report is the first to highlight the role of linezolid in streptococcal necrotizing fasciitis and TSS not improving with standard therapy.

  4. 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.

  5. 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.

  6. 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.

  7. Design of a Dynamic Spinal Implant for the treatment of Early Onset Scoliosis

    Energy Technology Data Exchange (ETDEWEB)

    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)

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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...

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. A SKIN TEST FOR DETECTING GROUP C HEMOLYTIC STREPTOCOCCAL INFECTION CAUSING EPIZOOTIC LYMPHADENITIS IN GUINEA PIGS : APPLICATIONS IN SELECTING BREEDING STOCK.

    Science.gov (United States)

    Moen, J K

    1936-09-30

    1. A skin test with a crude bacterial extract prepared from group C (Lancefield) hemolytic streptococci was used as a means of detecting possible carriers of the streptococcus causing epizootic lymphadenitis in guinea pigs. A positive test similar to a positive tuberculin reaction was considered presumptive evidence of present or recent infection with this streptococcus. 2. 20 positive reactors were found in 330 supposedly normal guinea pigs. 3. 195 negatively reacting animals were used as a breeding stock which yielded 1,296 progeny over a period of 15 months. None of the breeding stock or their progeny showed evidence of spontaneous lymphadenitis. Skin tests of 100 of the progeny were all negative. 4. The use of this skin test as a means of obtaining guinea pig breeding stock free of the streptococcus causing spontaneous lymphadenitis is suggested.

  18. 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.

  19. 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

  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. [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.

  3. 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

  4. 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.

  5. Bone mineral density in partially recovered early onset anorexic patients - a follow-up investigation

    Directory of Open Access Journals (Sweden)

    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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. A less invasive approach to screening for early onset neonatal GBS.

    LENUS (Irish Health Repository)

    Glackin, S

    2015-03-01

    Recent recommendations for the management of an asymptomatic term infant with one septic risk factor for Group B Streptococcal (GBS) invasive disease have advised a clinical approach. Following a previous audit in our unit which showed that high numbers of asymptomatic infants were receiving antibiotics, a new protocol was introduced which emphasised the importance of clinical examination. This study assessed the safety and efficacy of this new protocol through chart review of 1855 eligible infants. We found a statistically significant decrease (P < 0.0001) from 444 (19%) to 121 (6.5%) in the total number of term infants who underwent septic evaluations and received antibiotics. 241 asymptomatic infants with one septic risk factor were managed conservatively. No eligible infants had GBS invasive disease during the three month study period. The new protocol is a safe and effective tool for evaluating infants at risk of GBS invasive disease.

  11. 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....

  12. Inflammasome/IL-1β Responses to Streptococcal Pathogens

    Directory of Open Access Journals (Sweden)

    Christopher N. LaRock

    2015-10-01

    Full Text Available Inflammation mediated by the inflammasome and the cytokine IL-1β are some of the earliest and most important alarms to infection. These pathways are responsive to the virulence factors that pathogens use to subvert immune processes, and thus are typically activated only by microbes with potential to cause severe disease. Among the most serious human infections are those caused by the pathogenic streptococci, in part because these species numerous strategies for immune evasion. Since the virulence factor armament of each pathogen is unique, the role of IL-1β and the pathways leading to its activation varies for each infection. This review summarizes the role of IL-1β during infections caused by streptococcal pathogens, with emphasis on emergent mechanisms and concepts countering paradigms determined for other organisms.

  13. Group G streptococcal myositis in a patient with myeloproliferative neoplasm

    Directory of Open Access Journals (Sweden)

    Monica Midha, MD MBS

    2016-01-01

    Full Text Available While many cases of streptococcal infection are due to Lancefield groups A and B, there has been a rise in reported cases of infections due to group G streptococcus. We present a case of an individual with a hematologic malignancy who developed myositis secondary to group G streptococcus, with no clearly identifiable source of infection. The patient was managed with antibiotic therapy rather than surgical intervention due to high surgical risk related to severe thrombocytopenia. Targeted antibiotics initiated early in the course of disease may prevent the need for surgical intervention. Early diagnosis and treatment are critical to avoid the high morbidity and mortality of life-threatening infections caused by group G streptococcus.

  14. GENES, IN ADDITION TO TOLL-LIKE RECEPTOR 2, PLAY A ROLE IN ANTIBACTERIAL DEFENSE TO STREPTOCOCCAL PNEUMONIA

    Science.gov (United States)

    Streptococcus infection in human populations continues to be a major cause of morbidity and mortality. To evaluate the effect of genetic background and toll-like receptor 2 (TLR2) on antibacterial defense to streptococcal infection, eight genetically diverse strains of mic...

  15. Novel ZBTB24 Mutation Associated with Immunodeficiency, Centromere Instability, and Facial Anomalies Type-2 Syndrome Identified in a Patient with Very Early Onset Inflammatory Bowel Disease.

    Science.gov (United States)

    Conrad, Máire A; Dawany, Noor; Sullivan, Kathleen E; Devoto, Marcella; Kelsen, Judith R

    2017-12-01

    Very early onset inflammatory bowel disease, diagnosed in children ≤5 years old, can be the initial presentation of some primary immunodeficiencies. In this study, we describe a 17-month-old boy with recurrent infections, growth failure, facial anomalies, and inflammatory bowel disease. Immune evaluation, whole-exome sequencing, karyotyping, and methylation array were performed to evaluate the child's constellation of symptoms and examination findings. Whole-exome sequencing revealed that the child was homozygous for a novel variant in ZBTB24, the gene associated with immunodeficiency, centromere instability, and facial anomalies type-2 syndrome. This describes the first case of inflammatory bowel disease associated with immunodeficiency, centromere instability, and facial anomalies type-2 syndrome in a child with a novel disease-causing mutation in ZBTB24 found on whole-exome sequencing.

  16. 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

  17. 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.

  18. 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

  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. 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...

  1. 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…

  2. 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…

  3. 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.

  4. 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

  5. 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.

  6. 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:

  7. 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

  8. 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. ...

  9. 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

  10. 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…

  11. 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

  12. Streptococcal necrotizing myositis: a case report and clinical review.

    Science.gov (United States)

    Hourmozdi, Justin J; Hawley, Dean A; Hadi, Christiane M; Tahir, Bilal; Seupaul, Rawle A

    2014-03-01

    Streptococcal necrotizing myositis, also known as gangrenous myositis, is a very rare and severe soft tissue infection that predominately involves skeletal muscle and, eventually, superficial fascia and surrounding tissues. The presentation is often nonspecific until the rapidly progressing clinical course becomes apparent. A high morbidity and mortality rate has been reported in the small number of cases since 1900. Despite several attempts to better define the different entities causing necrotizing myositis, no single definitive causal relationship has been defined. A review of the literature is presented here to help clinicians distinguish those with necrotizing myositis from those with nonnecrotizing myositis when the clinician is at all confronted with the suspicion for such an infection. The case presented is that of a 48-year-old woman who had streptococcal necrotizing myositis. She died roughly 72 h after admission. After the patient's death, the clinical team sought consent for autopsy. Hospital staff made contact with family, and information was obtained from the family that the onset of the patient's symptoms was allegedly temporally related to her acquisition of a new tattoo on the right back, where the tattoo process allegedly included injection of cremated ashes of a pet dog. A high level of suspicion for necrotizing myositis must be maintained for a patient with unexplained severe muscle pain and soft tissue swelling accompanied by systemic inflammatory response syndrome. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. 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.

  14. 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.

  15. 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

  16. 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)

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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).

  2. 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.

  3. 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.

  4. 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

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  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. 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.

  14. 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.

  15. A high degree of LINE-1 hypomethylation is a unique feature of early-onset colorectal cancer.

    Directory of Open Access Journals (Sweden)

    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.

  16. Scarlet Fever: A Group A Streptococcal Infection

    Science.gov (United States)

    ... PDF file Microsoft PowerPoint file Microsoft Word file Microsoft ... Diseases , Division of Bacterial Diseases Page maintained by: Office of the Associate Director for Communication, Digital Media ...

  17. Use of the S-hook for Pelvic Fixation in Rib-Based Treatment of Early-Onset Scoliosis: A Multicenter Study.

    Science.gov (United States)

    Ramirez, Norman; Flynn, John M; Smith, John T; Vitale, Michael; Sturm, Peter F; DʼAmato, Charles; Samdani, Amer; Machiavelli, Raul; El-Hawary, Ron

    2015-06-01

    Retrospective review. The purpose of this study was to evaluate how several preoperative variables affect the outcome using the rib-to-pelvis S-hook constructs of a rib-based distraction implant (Vertical Expandable Prosthetic Titanium Rib). Rib-to-pelvis fixation with S-hooks is one of the options for distal anchoring of rib-based distraction growing rod construct to control early-onset spinal deformity. Since the initial report, the indications of pelvic fixation with S-hooks have been extended and modified. This is an institutional review board-approved retrospective study of patients who underwent rib-based growing rod system surgery-rib-to-pelvis construct with Dunn-McCarthy S-hook. Data evaluation included history, physical examination, preoperative and postoperative radiographs, surgical variables, and complications. Sixty-five patients were evaluated; 38 were male and 27 were female. Mean age at initial procedure was 71 months. The mean follow-up was 46 months. There was a statistically significant improvement of the immediate postoperative Cobb angle and the last follow-up Cobb angle (P < 0.0001). Fifty percent of the patients (32/65) had S-hook-related complications. The most common complication was sliding of the S-hook out of the iliac crest, followed by infection, neuropathic pain, distal migration of more than 2 cm, fracture of the hook, and bursitis. The complications were related to the preoperative ambulatory status, the use of end-to-end rod connectors, surgical time, and not positioning the hook over the central one-third of the iliac crest at the initial implantation. The use of the S-hook as a pelvic attachment of the rib-based system is indicated in nonambulatory patients with progressive, early-onset scoliosis curve with a lack of adequate anchor at the lumbar spine. Several technical factors should be considered to reduce the complication rate. 3.

  18. 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.

  19. 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.)

  20. 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.

  1. Results of the spine-to-rib-cage distraction in the treatment of early onset scoliosis

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    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.

  2. 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.

  3. 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.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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....

  11. 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

  12. 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.

  13. 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)

  14. Epidural Brain Metastases in a Patient with Early Onset Pancreatic Cancer: A Case Report and Literature Review

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    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.

  15. Loss of SYNJ1 dual phosphatase activity leads to early onset refractory seizures and progressive neurological decline

    DEFF Research Database (Denmark)

    Hardies, Katia; Cai, Yiying; Jardel, Claude

    2016-01-01

    SYNJ1 encodes a polyphosphoinositide phosphatase, synaptojanin 1, which contains two consecutive phosphatase domains and plays a prominent role in synaptic vesicle dynamics. Autosomal recessive inherited variants in SYNJ1 have previously been associated with two different neurological diseases...... with intractable epilepsy and tau pathology. We performed whole exome or genome sequencing in three independent sib pairs with early onset refractory seizures and progressive neurological decline, and identified novel segregating recessive SYNJ1 defects. A homozygous missense variant resulting in an amino acid...

  16. Development of a Multivariate Prediction Model for Early-Onset Bronchiolitis Obliterans Syndrome and Restrictive Allograft Syndrome in Lung Transplantation

    Directory of Open Access Journals (Sweden)

    Angela Koutsokera

    2017-07-01

    Full Text Available BackgroundChronic lung allograft dysfunction and its main phenotypes, bronchiolitis obliterans syndrome (BOS and restrictive allograft syndrome (RAS, are major causes of mortality after lung transplantation (LT. RAS and early-onset BOS, developing within 3 years after LT, are associated with particularly inferior clinical outcomes. Prediction models for early-onset BOS and RAS have not been previously described.MethodsLT recipients of the French and Swiss transplant cohorts were eligible for inclusion in the SysCLAD cohort if they were alive with at least 2 years of follow-up but less than 3 years, or if they died or were retransplanted at any time less than 3 years. These patients were assessed for early-onset BOS, RAS, or stable allograft function by an adjudication committee. Baseline characteristics, data on surgery, immunosuppression, and year-1 follow-up were collected. Prediction models for BOS and RAS were developed using multivariate logistic regression and multivariate multinomial analysis.ResultsAmong patients fulfilling the eligibility criteria, we identified 149 stable, 51 BOS, and 30 RAS subjects. The best prediction model for early-onset BOS and RAS included the underlying diagnosis, induction treatment, immunosuppression, and year-1 class II donor-specific antibodies (DSAs. Within this model, class II DSAs were associated with BOS and RAS, whereas pre-LT diagnoses of interstitial lung disease and chronic obstructive pulmonary disease were associated with RAS.ConclusionAlthough these findings need further validation, results indicate that specific baseline and year-1 parameters may serve as predictors of BOS or RAS by 3 years post-LT. Their identification may allow intervention or guide risk stratification, aiming for an individualized patient management approach.

  17. Academic Skills in Children with Early-Onset Type 1 Diabetes: The Effects of Diabetes-Related Risk Factors

    Science.gov (United States)

    Hannonen, Riitta; Komulainen, Jorma; Riikonen, Raili; Ahonen, Timo; Eklund, Kenneth; Tolvanen, Asko; Keskinen, Paivi; Nuuja, Anja

    2012-01-01

    Aim: The study aimed to assess the effects of diabetes-related risk factors, especially severe hypoglycaemia, on the academic skills of children with early-onset type 1 diabetes mellitus (T1DM). Method: The study comprised 63 children with T1DM (31 females, 32 males; mean age 9y 11mo, SD 4mo) and 92 comparison children without diabetes (40…

  18. 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.

  19. Novel mutations in the BRCA1 and BRCA2 genes in Iranian women with early-onset breast cancer

    International Nuclear Information System (INIS)

    Yassaee, Vahid R; Zeinali, Sirous; Harirchi, Iraj; Jarvandi, Soghra; Mohagheghi, Mohammad A; Hornby, David P; Dalton, Ann

    2002-01-01

    Breast cancer is the most common female malignancy and a major cause of death in middle-aged women. So far, germline mutations in the BRCA1 and BRCA2 genes in patients with early-onset breast and/or ovarian cancer have not been identified within the Iranian population. With the collaboration of two main centres for cancer in Iran, we obtained clinical information, family history and peripheral blood from 83 women under the age of 45 with early-onset breast cancer for scanning of germline mutations in the BRCA1 and BRCA2 genes. We analysed BRCA1 exons 11 and BRCA2 exons 10 and 11 by the protein truncation test, and BRCA1 exons 2, 3, 5, 13 and 20 and BRCA2 exons 9, 17, 18 and 23 with the single-strand conformation polymorphism assay on genomic DNA amplified by polymerase chain reaction. Ten sequence variants were identified: five frameshifts (putative mutations – four novel); three missense changes of unknown significance and two polymorphisms, one seen commonly in both Iranian and British populations. Identification of these novel mutations suggests that any given population should develop a mutation database for its programme of breast cancer screening. The pattern of mutations seen in the BRCA genes seems not to differ from other populations studied. Early-onset breast cancer (less than 45 years) and a limited family history is sufficient to justify mutation screening with a detection rate of over 25% in this group, whereas sporadic early-onset breast cancer (detection rate less than 5%) is unlikely to be cost-effective

  20. Serum Levels of Platelet Released CD40 Ligand Are Increased in Early Onset Occlusive Carotid Artery Disease

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    József Balla

    2006-01-01

    Full Text Available Objective: Soluble CD40 ligand (sCD40L has been suggested as a key mediator between inflammation and atherosclerosis, and the CD40-CD40L interaction has a role in atherosclerotic lesion progression. We evaluated if platelet released serum sCD40L and sCD40 levels differ between patients with early onset occlusive carotid artery disease and age-matched controls.

  1. Diagnostic delays in children with early-onset epilepsy: impact, reasons, and opportunities to improve care

    Science.gov (United States)

    Berg, Anne T.; Loddenkemper, Tobias; Baca, Christine B.

    2014-01-01

    Purpose Delayed diagnosis of early-onset epilepsy is a potentially important and avoidable complication in epilepsy care. We examined the frequency of diagnostic delays in young children with newly presenting epilepsy, their developmental impact, and reasons for delays. Methods Children who developed epilepsy before their third birthday were identified in a prospective community-based cohort. An interval ≥1 month from second seizure to diagnosis was considered a delay. Testing of development at baseline and for up to three years after and of IQ 8–9 years later was performed. Detailed parental baseline interview accounts and medical records were reviewed to identify potential reasons for delays. Factors associated with delays included the parent, child, pediatrician, neurologist, and scheduling. Results Diagnostic delays occurred in 70/172 (41%) children. Delays occurred less often if children had received medical attention for the first seizure (p<0.0001), previously had neonatal or febrile seizures (p=0.02), had only convulsions before diagnosis (p=0.005) or had a college-educated parent (p=0.01). A ≥1 month diagnostic delay was associated with an average 7.4 point drop (p=0.02) in the Vineland Scales of Adaptive Behavior motor score. The effect was present at diagnosis, persisted for at least three years, and was also apparent in IQ scores 8–9 years later which were lower in association with a diagnostic delay by 8.4 points (p=0.06) for processing speed up to 14.5 points (p=0.004) for full scale IQ, after adjustment for parental education and other epilepsy-related clinical factors. Factors associated with delayed diagnosis included parents not recognizing events as seizures (N=47), pediatricians missing or deferring diagnosis (N=15), neurologists deferring diagnosis (N=7), and scheduling problems (N=11). Significance Diagnostic delays occur in many young children with epilepsy. They are associated with substantial decrements in development and IQ later

  2. Serial Derotational Casting in Idiopathic and Non-Idiopathic Progressive Early-Onset Scoliosis.

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    Gussous, Yazeed M; Tarima, Sergey; Zhao, Shi; Khan, Safdar; Caudill, Angela; Sturm, Peter; Hammerberg, Kim W

    2015-05-01

    Serial derotational casting has been used as a definitive treatment or as delaying strategy in progressive idiopathic (IS) and non-idiopathic (NIS) early-onset scoliosis (EOS). Retrospective chart and radiographic review of patients who underwent serial casting for progressive EOS between 2005 and 2012 at a single institution. A total of 74 consecutive patients entered serial cast treatment. Twenty-eight were currently being casted, 30 completed cast treatment and were converted to thoracolumbosacral orthosis (TLSO), 9 were treated surgically, 6 were lost to follow-up, and 1 had no further treatment. The researchers diagnosed IS in 41 patients; 33 had NIS. At presentation the IS group had an average Cobb angle (CA) of 49° and a rib vertebral angle difference (RVAD) of 37°. The NIS group had a CA of 51° (p = .69) and RVAD of 37° (p = .94). In patients currently being casted, 19 IS patients had a decreased CA, from 47° to 27°. The 9 NIS patients had a decreased CA, from 62° to 57° (p = .0002). Cobb angle improvement was significantly better in IS (p = .0005). In the TLSO group the 17 IS patients had a decreased average CA, from 46° to 18°, after serial casting and the 13 NIS patients decreased CA from 42° to 32°. Patients with IS had better improvement in CA than the NIS group (p Casting initiated before age 2 years yielded better curve correction for IS (p casting than NIS patients. Casting in IS patients before age 24 months yielded better curve correction. Patients who required surgery had a higher age and Cobb angle at presentation than those who transitioned to a TLSO. The surgical group was observed for a similar duration of time and there was no significant statistical difference. Although RVAD is a predictor of progression in infantile IS, it did not show a predictive value in the response to casting of either the IS or NIS groups. Copyright © 2015 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.

  3. The role of serial casting in early-onset scoliosis (EOS).

    Science.gov (United States)

    Baulesh, David M; Huh, Jeannie; Judkins, Timothy; Garg, Sumeet; Miller, Nancy H; Erickson, Mark A

    2012-01-01

    Serial casting has demonstrated efficacy for idiopathic early-onset scoliosis (EOS). Results of casting in nonidiopathic (syndromic and congenital) EOS patients have not previously been well described. A total of 53 patients underwent serial casting for EOS from 2005 to 2010 at a single institution. Deformity was classified as idiopathic or nonidiopathic. Diagnosis, time in cast, number of casts, use of bracing, complications, and outcomes were recorded. Radiographic measures included Cobb angle and thoracic height (T1-T12). Thoracic height velocity was calculated and compared with established norms. A total of 36 patients, 19 idiopathic and 17 nonidiopathic (14 syndromic, 3 congenital), completed cast treatment and had >6-month follow-up and were therefore included. Of those, 17% (6/36) experienced resolution of their deformity, 53% (19/26) are currently in braces, and 31% (11/36) had undergone surgery. Surgery occurred on average at age 5.6 years and was delayed by an average of 2.1 years from time of first cast. A 19% complication was observed. There was no statistical difference in the rate of resolution of deformity between idiopathic (5/19) and nonidiopathic (1/17) patients (P=0.182), although there exists a trend toward greater curve correction in idiopathic patients. Surgery occurred in fewer patients (2/19) in the idiopathic group compared with the nonidiopathic group (9/17) (P=0.006). Significant improvements in Cobb angle was observed in the idiopathic group (12.2 degrees) during casting (P=0.003). Nonidiopathic patients did not maintain the correction gained during casting at the time of final follow-up. T1-T12 height increased across all study patients regardless of etiology during the period of casting at similar velocity to established norms of 1.4 cm/y for this age group. Serial casting offers modest deformity correction in idiopathic deformities compared with nonidiopathic deformities. Thoracic height growth continued throughout the casting period

  4. 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

  5. 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

  6. 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

  7. Parental R-Rated Movie Restriction and Early-Onset Alcohol Use*

    Science.gov (United States)

    Tanski, Susanne E.; Dal Cin, Sonya; Stoolmiller, Mike; Sargent, James D.

    2010-01-01

    Objective: The aim of this study was to determine if parental restriction regarding Restricted-rated movies (R movies) predicts lower rates of early-onset alcohol use. Method: Students from 15 northern New England middle schools were surveyed in 1999, and never-drinkers were resurveyed 13–26 months later to determine alcohol use. Drinking was determined by the question, “Have you ever had beer, wine, or other drink with alcohol that your parents didn't know about?” R-movie restriction was assessed by the question, “How often do your parents allow you to watch movies that are rated R?” Results: The sample included 2,406 baseline never-drinkers who were surveyed at follow-up, of whom 14.8% had initiated alcohol use. At baseline, 20% reported never being allowed to watch R movies, and 21% reported being allowed all the time. Adolescents allowed to watch R-rated movies had higher rates of alcohol initiation (2.9% initiation among never allowed, 12.5% once in a while, 18.8% sometimes, and 24.4% all the time). Controlling for sociodemographics, personality characteristics, and authoritative parenting style, the adjusted odds ratios for initiating alcohol use were 3.0 (95% CI [1.7, 5.1]) for those once in a while allowed, 3.3 [1.9, 5.6] for those sometimes allowed, and 3.5 [2.0, 6.0] for those always allowed to watch R-rated movies. Alcohol initiation was more likely if R-rated movie restriction relaxed over time; tightening of restriction had a protective effect (p authoritative parenting and (b) media parenting. Both constructs had direct inverse paths to trying alcohol and indirect paths through lower exposure to R-rated movies. Conclusions: After accounting for differences in authoritative parenting style, adolescents reporting lesser restrictions for R movies have higher odds of future alcohol use. The structural model suggests that media parenting operates independently from authoritative parenting and should be incorporated explicitly into parenting

  8. Parental R-rated movie restriction and early-onset alcohol use.

    Science.gov (United States)

    Tanski, Susanne E; Dal Cin, Sonya; Stoolmiller, Mike; Sargent, James D

    2010-05-01

    The aim of this study was to determine if parental restriction regarding Restricted-rated movies (R movies) predicts lower rates of early-onset alcohol use. Students from 15 northern New England middle schools were surveyed in 1999, and never-drinkers were resurveyed 13-26 months later to determine alcohol use. Drinking was determined by the question, "Have you ever had beer, wine, or other drink with alcohol that your parents didn't know about?" R-movie restriction was assessed by the question, "How often do your parents allow you to watch movies that are rated R?" The sample included 2,406 baseline never-drinkers who were surveyed at follow-up, of whom 14.8% had initiated alcohol use. At baseline, 20% reported never being allowed to watch R movies, and 21% reported being allowed all the time. Adolescents allowed to watch R-rated movies had higher rates of alcohol initiation (2.9% initiation among never allowed, 12.5% once in a while, 18.8% sometimes, and 24.4% all the time). Controlling for sociodemographics, personality characteristics, and authoritative parenting style, the adjusted odds ratios for initiating alcohol use were 3.0 (95% CI [1.7, 5.1]) for those once in a while allowed, 3.3 [1.9, 5.6] for those sometimes allowed, and 3.5 [2.0, 6.0] for those always allowed to watch R-rated movies. Alcohol initiation was more likely if R-rated movie restriction relaxed over time; tightening of restriction had a protective effect (p authoritative parenting and (b) media parenting. Both constructs had direct inverse paths to trying alcohol and indirect paths through lower exposure to R-rated movies. After accounting for differences in authoritative parenting style, adolescents reporting lesser restrictions for R movies have higher odds of future alcohol use. The structural model suggests that media parenting operates independently from authoritative parenting and should be incorporated explicitly into parenting prevention programs.

  9. Voxel-based structural magnetic resonance imaging (MRI study of patients with early onset schizophrenia

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    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

  10. 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

  11. Temporal-lobe morphology differs between healthy adolescents and those with early-onset of depression

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    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

  12. Molecular Features and Methylation Status in Early Onset (≤40 Years Colorectal Cancer: A Population Based, Case-Control Study

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    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.

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

    Science.gov (United States)

    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.

  14. 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.)

  15. A novel CDKL5 mutation in a 47,XXY boy with the early-onset seizure variant of Rett syndrome.

    Science.gov (United States)

    Sartori, Stefano; Di Rosa, Gabriella; Polli, Roberta; Bettella, Elisa; Tricomi, Giovanni; Tortorella, Gaetano; Murgia, Alessandra

    2009-02-01

    Mutations of the cyclin-dependent kinase-like 5 gene (CDKL5), reported almost exclusively in female subjects, have been recently found to be the cause of a phenotype overlapping Rett syndrome with early-onset epileptic encephalopathy. We describe the first CDKL5 mutation detected in a male individual with 47,XXY karyotype. This previously unreported, de novo, mutation truncates the large CDKL5 COOH-terminal region, thought to be crucial for the proper sub-cellular localization of the CDKL5 protein. The resulting phenotype is characterized by a severe early-onset epileptic encephalopathy, global developmental delay, and profound intellectual and motor impairment with features reminiscent of Rett syndrome. In light of the data presented we discuss the possible phenotypic modulatory effects of the supernumerary wild type X allele and pattern of X chromosome inactivation and stress the importance of considering the causal involvement of CDKL5 in developmentally delayed males with early-onset seizures. (c) 2009 Wiley-Liss, Inc.

  16. A New Nonsense Mutation in CDKL5 Gene in a Male Patient with Early Onset Refractory Epilepsy: a Case Report

    Directory of Open Access Journals (Sweden)

    Soudeh Ghafouri-Fard

    2016-02-01

    Full Text Available Background The X-linked cyclin-dependent kinase like 5 (CDKL5/STK9 gene has been shown to be responsible for a severe encephalopathy condition characterized by early onset of epilepsy and severe developmental delay. CDKL5 mutations have been shown to be more frequent among female patients. Results Here we report a 6- month male patient, second child of a healthy non consanguineous in the Iranian population. He has been affected by early onset epileptic refractory seizures and developmental delay. Whole-exome sequencing (WES has revealed a base substitution c.173T>A in CDKL5 gene, resulting in the formation of stop codon p.L58X. This mutation resides in the catalytic domain of the corresponding protein and is expected to result in premature RNA break down with no CDKL5 resulting protein. Conclusion   The present report highlights the importance of CDKL5 mutation analysis in male patients affected with early onset refractory epilepsy.

  17. 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.

  18. 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.

  19. Genetic Analysis of PARK2 and PINK1 Genes in Brazilian Patients with Early-Onset Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Karla Cristina Vasconcelos Moura

    2013-01-01

    Full Text Available Parkinson's disease is the second most frequent neurodegenerative disorder in the world, affecting 1-2% of individuals over the age of 65. The etiology of Parkinson's disease is complex, with the involvement of gene-environment interactions. Although it is considered a disease of late manifestation, early-onset forms of parkinsonism contribute to 5–10% of all cases. In the present study, we screened mutations in coding regions of PARK2 and PINK1 genes in 136 unrelated Brazilian patients with early-onset Parkinson's disease through automatic sequencing. We identified six missense variants in PARK2 gene: one known pathogenic mutation, two variants of uncertain role, and three nonpathogenic changes. No pathogenic mutation was identified in PINK1 gene, only benign polymorphisms. All putative pathogenic variants found in this study were in heterozygous state. Our data show that PARK2 point mutations are more common in Brazilian early-onset Parkinson's disease patients (2.9% than PINK1 missense variants (0%, corroborating other studies worldwide.

  20. 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.

  1. Behavioral, Pharmacological, and Immunological Abnormalities after Streptococcal Exposure: A Novel Rat Model of Sydenham Chorea and Related Neuropsychiatric Disorders

    Science.gov (United States)

    Brimberg, Lior; Benhar, Itai; Mascaro-Blanco, Adita; Alvarez, Kathy; Lotan, Dafna; Winter, Christine; Klein, Julia; Moses, Allon E; Somnier, Finn E; Leckman, James F; Swedo, Susan E; Cunningham, Madeleine W; Joel, Daphna

    2012-01-01

    Group A streptococcal (GAS) infections and autoimmunity are associated with the onset of a spectrum of neuropsychiatric disorders in children, with the prototypical disorder being Sydenham chorea (SC). Our aim was to develop an animal model that resembled the behavioral, pharmacological, and immunological abnormalities of SC and other streptococcal-related neuropsychiatric disorders. Male Lewis rats exposed to GAS antigen exhibited motor symptoms (impaired food manipulation and beam walking) and compulsive behavior (increased induced-grooming). These symptoms were alleviated by the D2 blocker haloperidol and the selective serotonin reuptake inhibitor paroxetine, respectively, drugs that are used to treat motor symptoms and compulsions in streptococcal-related neuropsychiatric disorders. Streptococcal exposure resulted in antibody deposition in the striatum, thalamus, and frontal cortex, and concomitant alterations in dopamine and glutamate levels in cortex and basal ganglia, consistent with the known pathophysiology of SC and related neuropsychiatric disorders. Autoantibodies (IgG) of GAS rats reacted with tubulin and caused elevated calcium/calmodulin-dependent protein kinase II signaling in SK-N-SH neuronal cells, as previously found with sera from SC and related neuropsychiatric disorders. Our new animal model translates directly to human disease and led us to discover autoantibodies targeted against dopamine D1 and D2 receptors in the rat model as well as in SC and other streptococcal-related neuropsychiatric disorders. PMID:22534626

  2. Invasive group A streptococcal disease in The Netherlands : Evidence for a protective role of anti-exotoxin A antibodies

    NARCIS (Netherlands)

    Mascini, EM; Jansze, M; Schellekens, JFP; Musser, JM; Faber, JAJ; Verhoef-Verhage, LAE; Schouls, L; van Leeuwen, WJ; Verhoef, J; van Dijk, H

    As part of a nationwide surveillance in The Netherlands during 1994-1997, 53 patients with invasive group A streptococcal (GAS) infections were evaluated for medical history, symptoms, and outcome. Patients' isolates were tested for the production of pyrogenic exotoxins A (SPE-A) and B (SPE-B).

  3. Streptococcal pyogenic exotoxin B (SpeB) boosts the contact system via binding of a-1 antitrypsin

    DEFF Research Database (Denmark)

    Meinert Niclasen, Louise; Olsen, Johan G; Dagil, Robert

    2011-01-01

    The Streptococcus pyogenes cysteine protease SpeB (streptococcal pyrogenic exotoxin B) is important for the invasive potential of the bacteria, but its production is down-regulated following systemic infection. This prompted us to investigate if SpeB potentiated the host immune response after sys...

  4. Structure of the Mature Streptococcal Cysteine Protease Exotoxin mSpeB in Its Active Dimeric Form

    DEFF Research Database (Denmark)

    Olsen, Johan G; Dagil, Robert; Niclasen, Louise Meinert

    2009-01-01

    Invasive infections of Streptococcus pyogenes are dependent on the cysteine protease streptococcal pyrogenic exotoxin B. Previous structures of the enzyme have not disclosed the proper active-site configuration. Here, the crystal structure of the mature enzyme is presented to 1.55 A, disclosing...

  5. Pneumococcal Infections: MedlinePlus Health Topic

    Science.gov (United States)

    ... Prevention, Immunization Action Coalition) - PDF Also in Spanish Topic Image MedlinePlus Email Updates Get Pneumococcal Infections updates ... ray Meningitis - pneumococcal Sputum gram stain Related Health Topics Meningitis Pneumonia Sepsis Sinusitis Streptococcal Infections National Institutes ...

  6. Early-Onset Alzheimer Disease and Candidate Risk Genes Involved in Endolysosomal Transport.

    Science.gov (United States)

    Kunkle, Brian W; Vardarajan, Badri N; Naj, Adam C; Whitehead, Patrice L; Rolati, Sophie; Slifer, Susan; Carney, Regina M; Cuccaro, Michael L; Vance, Jeffery M; Gilbert, John R; Wang, Li-San; Farrer, Lindsay A; Reitz, Christiane; Haines, Jonathan L; Beecham, Gary W; Martin, Eden R; Schellenberg, Gerard D; Mayeux, Richard P; Pericak-Vance, Margaret A

    2017-09-01

    Mutations in APP, PSEN1, and PSEN2 lead to early-onset Alzheimer disease (EOAD) but account for only approximately 11% of EOAD overall, leaving most of the genetic risk for the most severe form of Alzheimer disease unexplained. This extreme phenotype likely harbors highly penetrant risk variants, making it primed for discovery of novel risk genes and pathways for AD. To search for rare variants contributing to the risk for EOAD. In this case-control study, whole-exome sequencing (WES) was performed in 51 non-Hispanic white (NHW) patients with EOAD (age at onset 65 years) from the Alzheimer's Disease Genetics Consortium. The study was conducted from January 21, 2013, to October 13, 2016. Alzheimer disease diagnosed according to standard National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer Disease and Related Disorders Association criteria. Association between Alzheimer disease and genetic variants and genes was measured using logistic regression and sequence kernel association test-optimal gene tests, respectively. Of the 1524 NHW patients with EOAD, 765 (50.2%) were women and mean (SD) age was 60.0 (4.9) years; of the 7046 NHW patients with LOAD, 4171 (59.2%) were women and mean (SD) age was 77.4 (8.6) years; and of the 7001 NHW controls, 4215 (60.2%) were women and mean (SD) age was 77.4 (8.6) years. The gene PSD2, for which multiple unrelated NHW cases had rare missense variants, was significantly associated with EOAD (P = 2.05 × 10-6; Bonferroni-corrected P value [BP] = 1.3 × 10-3) and LOAD (P = 6.22 × 10-6; BP = 4.1 × 10-3). A missense variant in TCIRG1, present in a NHW patient and segregating in 3 cases of a Hispanic family, was more frequent in EOAD cases (odds ratio [OR], 2.13; 95% CI, 0.99-4.55; P = .06; BP = 0.413), and significantly associated with LOAD (OR, 2.23; 95% CI, 1.37-3.62; P = 7.2 × 10-4; BP = 5.0 × 10-3). A missense variant in the LOAD risk

  7. Recurrent group A streptococcal vulvovaginitis in adult women: family epidemiology.

    Science.gov (United States)

    Sobel, Jack D; Funaro, Deana; Kaplan, Edward L

    2007-03-01

    Group A beta-hemolytic streptococcal (GAS) vulvovaginitis has been reported in prepubertal girls. In adult women, a vaginal carrier state has been described, but vulvovaginitis is rarely reported. We describe 2 cases of recurrent GAS vulvovaginitis in women whose husbands were gastrointestinal carriers of GAS. Characterization of the isolated strains demonstrated that identical emm types of GAS were shared by partners. Treatment of both partners resulted in resolution of vaginitis. On the basis of negative vaginal culture results obtained after treatment of each individual episode of vaginitis, we believe that the female patients were reinfected as a result of exposure to their husbands, with shedding likely to have occurred in bed. These cases reiterate the necessity for adequate screening of the patient's family and contacts in cases of recurrent GAS infection by culturing all potential areas of GAS carriage.

  8. 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

  9. Copy number variations in "classical" obesity candidate genes are not frequently associated with severe early-onset obesity in children.

    Science.gov (United States)

    Windholz, Jan; Kovacs, Peter; Schlicke, Marina; Franke, Christin; Mahajan, Anubha; Morris, Andrew P; Lemke, Johannes R; Klammt, Jürgen; Kiess, Wieland; Schöneberg, Torsten; Pfäffle, Roland; Körner, Antje

    2017-05-01

    Obesity is genetically heterogeneous and highly heritable, although polymorphisms explain the phenotype in only a small proportion of obese children. We investigated the presence of copy number variations (CNVs) in "classical" genes known to be associated with (monogenic) early-onset obesity in children. In 194 obese Caucasian children selected for early-onset and severe obesity from our obesity cohort we screened for deletions and/or duplications by multiplex ligation-dependent probe amplification reaction (MLPA). As we found one MLPA probe to interfere with a polymorphism in SIM1 we investigated its association with obesity and other phenotypic traits in our extended cohort of 2305 children. In the selected subset of most severely obese children, we did not find CNV with MLPA in POMC, LEP, LEPR, MC4R, MC3R or MC2R genes. However, one SIM1 probe located at exon 9 gave signals suggestive for SIM1 insufficiency in 52 patients. Polymerase chain reaction (PCR) analysis identified this as a false positive result due to interference with single nucleotide polymorphism (SNP) rs3734354/rs3734355. We, therefore, investigated for associations of this polymorphism with obesity and metabolic traits in our extended cohort. We found rs3734354/rs3734355 to be associated with body mass index-standard deviation score (BMI-SDS) (p = 0.003), but not with parameters of insulin metabolism, blood pressure or food intake. In our modest sample of severely obese children, we were unable to find CNVs in well-established monogenic obesity genes. Nevertheless, we found an association of rs3734354 in SIM1 with obesity of early-onset type in children, although not with obesity-related traits.

  10. The psychopathological and psychosocial outcome of early-onset schizophrenia: Preliminary data of a 13-year follow-up

    Directory of Open Access Journals (Sweden)

    Mehler-Wex Claudia

    2008-02-01

    Full Text Available Abstract Background Relatively little is known about the long-term psychopathological and psychosocial outcome of early-onset schizophrenia. The existing literature describes more severe courses of illness in these patients compared with adult-onset schizophrenia. This article reports preliminary data of a study exploring the outcome of early-onset schizophrenia 13.4 years (mean after first admission. Predictors for interindividual outcomes were investigated. Methods We retrospectively assessed 27 former patients (mean age at first admission 15.5 years, SD = 2.0 that were consecutively admitted to the Department of Child and Adolescent Psychiatry at the University of Wuerzburg between 1990 and 2000. A multidimensional approach was chosen to assess the outcome consisting of a mail survey including different questions about psychopathological symptoms, psychosocial parameters, and standardized self-reports (ESI and ADS. Results Concerning the psychopathological outcome, 22.2% reported having acute schizophrenic symptoms. Almost one third (30.8% described symptoms of depression and 37.0% reported having tried to commit suicide or seriously thought about it. 77.8% of the former patients were still in outpatient treatment. Compared to the general population, the number of patients without a school graduation was relatively high (18.5%. Almost half of participants still live with their parents (48.1% or in assisted or semi-assisted living conditions (33.3%. Only 18.5% were working in the open market. Conclusion Schizophrenia with an early onset has an unfavourable prognosis. Our retrospective study of the psychopathological and psychosocial outcome concludes with a generally poor rating.

  11. Hypoglycemic action of vitamin K1 protects against early-onset diabetic nephropathy in streptozotocin-induced rats.

    Science.gov (United States)

    Sai Varsha, M K N; Raman, Thiagarajan; Manikandan, R; Dhanasekaran, G

    2015-10-01

    Vitamin K is a potent regulator of vascular dynamics and prevents vascular calcification. Vitamin K is increasingly being recognized for its antioxidant and antiinflammatory properties. Recently we demonstrated that vitamin K1 (5 mg/kg) protects against streptozotocin-induced type 1 diabetes and diabetic cataract. The aim of this study was to determine whether the hypoglycemic action of vitamin K1 could inhibit early-onset diabetic nephropathy in a streptozotocin-induced rat kidney. Male Wistar rats were administered with 35 mg/kg STZ and after 3 days were treated with vitamin K1 (5 mg/kg, twice a week) for 3 months. Blood glucose was monitored once a month. At the end of the study, animals were sacrificed and kidney was dissected out and analysed for free radicals, antioxidants, aldose reductase, membrane ATPases, histopathology evaluation and expression of pro- and anti-inflammatory cytokines. Urea, uric acid, creatinine, albumin and insulin levels were also estimated. Treatment of diabetic rats with vitamin K1 resulted in a decrease in blood glucose and prevented microalbuminuria. Vitamin K1 also reduced oxidative stress and protected renal physiology by modulating Ca(2+) and Na(+)/K(+)-ATPases. Vitamin K1 inhibited renal inflammation by reducing nuclear factor-κB and inducible nitric oxide synthase. Interleukin-10 levels were increased in renal tissues, suggesting the ability of vitamin K1 to trigger antiinflammatory state. The hypoglycemic action of vitamin K1 could have an indirect effect by inhibiting early-onset diabetic nephropathy triggered by high blood glucose. Vitamin K1 could be an important nutrient based interventional strategy for early onset diabetic nephropathy. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. 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...

  13. Precision-cut liver slices as a model for the early onset of liver fibrosis to test antifibrotic drugs

    Energy Technology Data Exchange (ETDEWEB)

    Westra, Inge M. [Division of Pharmacokinetics, Toxicology and Targeting, Department of Pharmacy, University of Groningen (Netherlands); Oosterhuis, Dorenda [Division of Pharmaceutical Technology and Biopharmacy, Department of Pharmacy, University of Groningen (Netherlands); Groothuis, Geny M.M. [Division of Pharmacokinetics, Toxicology and Targeting, Department of Pharmacy, University of Groningen (Netherlands); Olinga, Peter, E-mail: p.olinga@rug.nl [Division of Pharmaceutical Technology and Biopharmacy, Department of Pharmacy, University of Groningen (Netherlands)

    2014-01-15

    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 48 h, viability was assessed by ATP and gene expression of PDGF-B and TGF-β1 and the fibrosis markers Hsp47, αSma and Pcol1A1 and collagen1 protein expressions were determined. The effects of the antifibrotic drugs imatinib, sorafenib and sunitinib, PDGF-pathway inhibitors, and perindopril, valproic acid, rosmarinic acid, tetrandrine and pirfenidone, TGFβ-pathway inhibitors, were determined. After 48 h of incubation, viability of the PCLS was maintained and gene expression of PDGF-B was increased while TGF-β1 was not changed. Hsp47, αSma and Pcol1A1 gene expressions were significantly elevated in PCLS after 48 h, which was further increased by PDGF-BB and TGF-β1. The increased gene expression of fibrosis markers was inhibited by all three PDGF-inhibitors, while TGFβ-inhibitors showed marginal effects. The protein expression of collagen 1 was inhibited by imatinib, perindopril, tetrandrine and pirfenidone. In conclusion, the increased gene expression of PDGF-B and the down-regulation of fibrosis markers by PDGF-pathway inhibitors, together with the absence of elevated TGF-β1 gene expression and the limited effect of the TGFβ-pathway inhibitors, indicated the predominance of the PDGF pathway in the early onset of fibrosis in PCLS. PCLS appear a useful model for research of the early onset of fibrosis and for testing of antifibrotic drugs acting on the PDGF pathway. - Highlights: • During culture, fibrosis markers increased in precision-cut liver slices (PCLS). • Gene expression of PDGF-β was increased, while TGFβ was not changed in rat PCLS. • PDGF-pathway inhibitors down-regulated this increase of fibrosis markers. • TGFβ-pathway inhibitors had only

  14. Increased steroidogenesis promotes early-onset and severe vision loss in females with OPA1 dominant optic atrophy

    DEFF Research Database (Denmark)

    Sarzi, Emmanuelle; Seveno, Marie; Angebault, Claire

    2016-01-01

    levels of steroid precursor pregnenolone in females, causing an early-onset vision loss, abolished by ovariectomy. In addition, steroid production in retina is also increased which, in conjunction with high circulating levels, impairs estrogen receptor expression and mitochondrial respiratory complex IV...... tested the hypothesis of deregulated steroid production in retina due to a disease-causing OPA1 mutation and its contribution to the visual phenotypic variations. Using the mouse model carrying the human recurrent OPA1 mutation, we disclosed that Opa1 haploinsufficiency leads to very high circulating...

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Prevalence and risk factors of early onset of sexual intercourse in a random sample of a multiethnic adolescent population in French Guiana.

    Science.gov (United States)

    Ayhan, Gülen; Martin, Loic; Levy-Loeb, Mathieu; Thomas, Stéphanie; Euzet, Géneviève; Van Melle, Astrid; Parriault, Marie-Claire; Basurko, Célia; Nacher, Mathieu

    2015-01-01

    French Guiana, a French overseas department in South America, has been classified epidemic for HIV. This territory is consisting of a very young population with almost 45% of them being younger than 20 years of age. Delaying the onset of first sexual intercourse (SI) is one of the major objectives to fight HIV infection in adolescents. The objective of this study is to identify the age of first SI and the risk factors of early onset. A behavioural surveillance survey among students living on the coastline and alongside the Maroni River was conducted in 2011/2012. A total of 1603 students filled out the survey. While 60% had already SI, the mean age of first intercourse was 12.1 years for boys and 13.9 years for girls. Accordingly, over 90% had a premature onset of SI. Risk factors are age, male gender, living alongside the Maroni River, another language than the French being mother tongue, not being religious, alcohol and cannabis consumption and a bad attitude towards condom use. Risk factors for girls are an older first sexual partner, having more than three lifetime sexual partners and condom rupture. Evidence-based implementation with respect of local and socio-demographic aspects is necessary to improve youths' appreciation of SI and related risk of sexual transmitted diseases.

  17. Group C streptococcal sepsis complicating Fournier gangrene.

    Science.gov (United States)

    Marinella, Mark A

    2005-09-01

    Fournier gangrene is a life-threatening necrotizing fasciitis of the perineal-scrotal area that occurs in diabetic males. Patients typically present with systemic toxicity and significant inflammatory changes in the scrotum and perineum. Most cases of Fournier gangrene are polymicrobic and require urgent surgical debridement and broad-spectrum antibiotic therapy. We describe a case of Fournier gangrene in a young diabetic man that was associated with group C streptococcal bacteremia, an association previously unreported in the literature to our knowledge.

  18. Low incidence of germline mutation in BRCA1 Exon 11 among early-onset and familial Filipino breast cancer patients

    International Nuclear Information System (INIS)

    Nato, Alejandro Q. Jr; Deocaris, Custer C.; Sajise, Sheila C.

    2002-01-01

    Breast cancer susceptibility gene, type 1 (BRCA1) has been thought to be responsible for about 45% of families with multiple breast carcinoma cases and for more than 80% of hereditary breast and ovarian cancer (HBOC) families. About 61-75% of the reported distinct alterations that result in truncated protein products have been found in exon 11 which comprises 61% (3427bp) of the coding sequence of BRCA1(5592bp). Protein truncation test (PTT) has become a popular method as an efficient means of screening mutations in a coding sequence that lead to a truncated protein product. In this study, 34 early-onset and/or familial breast cancer (FBC) patients were investigated. Twenty-six patients are early-onset B(o)C cases (diagnosed≤40 years old), 14 of which have familiality of the disease. Among the 8 patients that have been diagnosed above 40 years old, 7 have familial clustering. Through radioactive PTT analysis of the 34 BC cases in a 5-20% denaturing gradient polyacrylamide gel, we found only one mutation in exon 11 having a 29.7 kDa truncated protein product. Our results corroborate the findings of a recently reported study of unselected incident breast cancer cases in the Philippines where the prevalence of BRCA1 mutation is also low. This would, however, be the second documented mutation in BRCA1 exon 11 in a Filipino BC patient since 1998. (author)

  19. Early-Onset Severe Encephalopathy with Epilepsy: The BRAT1 Gene Should Be Added to the List of Causes.

    Science.gov (United States)

    van de Pol, Laura A; Wolf, Nicole I; van Weissenbruch, Mirjam M; Stam, Cornelie J; Weiss, Janneke M; Waisfisz, Quinten; Kevelam, Sietske H; Bugiani, Mariana; van de Kamp, Jiddeke M; van der Knaap, Marjo S

    2015-12-01

    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 attempt to identify gene defects in patients suspected to suffer from a genetic form. We describe three siblings, born to consanguineous parents, with a lethal severe epileptic encephalopathy with early-infantile onset, including their magnetic resonance imaging, electroencephalography and, in one case, neuropathological findings. Using WES a homozygous frameshift mutation in the BRAT1 gene, c.638dup p.(Val214Glyfs*189), was identified. We present our cases in the context of all published cases with mutations in the BRAT1 gene and conclude that BRAT1 should be added to the growing list of genes related to early-onset severe encephalopathy with epilepsy. Georg Thieme Verlag KG Stuttgart · New York.

  20. Detection of Fetomaternal Genotype Associations in Early-Onset Disorders: Evaluation of Different Methods and Their Application to Childhood Leukemia

    Directory of Open Access Journals (Sweden)

    Jasmine Healy

    2010-01-01

    Full Text Available Several designs and analytical approaches have been proposed to dissect offspring from maternal genetic contributions to early-onset diseases. However, lack of parental controls halts the direct verification of the assumption of mating symmetry (MS required to assess maternally-mediated effects. In this study, we used simulations to investigate the performance of existing methods under mating asymmetry (MA when parents of controls are missing. Our results show that the log-linear, likelihood-based framework using a case-triad/case-control hybrid design provides valid tests for maternal genetic effects even under MA. Using this approach, we examined fetomaternal associations between 29 SNPs in 12 cell-cycle genes and childhood pre-B acute lymphoblastic leukemia (ALL. We identified putative fetomaternal effects at loci CDKN2A rs36228834 (P=.017 and CDKN2B rs36229158 (P=.022 that modulate the risk of childhood ALL. These data further corroborate the importance of the mother's genotype on the susceptibility to early-onset diseases.

  1. Targeted next generation sequencing identifies functionally deleterious germline mutations in novel genes in early-onset/familial prostate cancer.

    Directory of Open Access Journals (Sweden)

    Paula Paulo

    2018-04-01

    Full Text Available Considering that mutations in known prostate cancer (PrCa predisposition genes, including those responsible for hereditary breast/ovarian cancer and Lynch syndromes, explain less than 5% of early-onset/familial PrCa, we have sequenced 94 genes associated with cancer predisposition using next generation sequencing (NGS in a series of 121 PrCa patients. We found monoallelic truncating/functionally deleterious mutations in seven genes, including ATM and CHEK2, which have previously been associated with PrCa predisposition, and five new candidate PrCa associated genes involved in cancer predisposing recessive disorders, namely RAD51C, FANCD2, FANCI, CEP57 and RECQL4. Furthermore, using in silico pathogenicity prediction of missense variants among 18 genes associated with breast/ovarian cancer and/or Lynch syndrome, followed by KASP genotyping in 710 healthy controls, we identified "likely pathogenic" missense variants in ATM, BRIP1, CHEK2 and TP53. In conclusion, this study has identified putative PrCa predisposing germline mutations in 14.9% of early-onset/familial PrCa patients. Further data will be necessary to confirm the genetic heterogeneity of inherited PrCa predisposition hinted in this study.

  2. The p. N103K mutation of leptin (LEP gene and severe early onset obesity in Pakistan

    Directory of Open Access Journals (Sweden)

    Shabana

    Full Text Available BACKGROUND: Obesity is a complex disorder and has been increasing globally at alarming rates including Pakistan. However, there is scarce research on understanding obesity genetics in Pakistan. Leptin is a hormone secreted by adipocytes in response to satiety and correlates with body weight. Any mutations in the LEP gene have an adverse effect on energy regulation pathway and lead to severe, early onset obesity. To date, only eight mutations have been described in the LEP gene of which p. N103K is one. METHODS: We aimed to analyze the prevalence of this mutation in Pakistani subjects. A total of 475 subjects were genotyped by PCR-RFLP analysis and their serum profiling was done. RESULTS: Results showed that this mutation was present only in one male child with early onset obesity (10 year. He had very low serum leptin levels suggestive of functional impact of the mutation. The prevalence of such mutations is, however, low due to the drastic effects on the energy regulation. CONCLUSION: In conclusion, LEP gene mutations contribute significantly to the monogenic forms of obesity and are important due to the availability of treatment options. Such mutations may exert their effect by directly affecting energy regulation pathway and are more prominent in the early stages of life only.

  3. Predicting early onset of intoxication versus drinking—A population-based prospective study of Norwegian adolescents

    Directory of Open Access Journals (Sweden)

    Frøydis Enstad

    2017-12-01

    Full Text Available Aims: Recent research suggests that early onset of intoxication (EOI may be of greater importance for a wide range of subsequent adverse outcomes than early drinking experiences without intoxication. However, research on antecedents of EOI is scarce. The present study identifies predictors of EOI and whether they differ from those of early onset of drinking (EOD. Methods: Data was drawn from the prospective Tracking Opportunities and Problems (TOPP study of Norwegian families (n=382, which followed up mothers and their children with six data collections from childhood (age 1.5 to adolescence (age 14.5. Self-reports from the adolescents (parenting practices, adolescent's conduct problems and friends' deviant behaviour and their mothers (adolescent temperament, socio-economic factors and household alcohol problems were used to identify predictors of EOI and EOD. Findings: A variety of temperamental, socio-economic, and family factors predicted EOI, whereas EOD was predicted of substantially fewer variables. Particularly, when controlling for relevant covariates, low levels of shyness, own conduct problems and having friends with deviant behaviour prospectively predicted EOI, but not EOD. Conclusions: Future research and prevention efforts should take into consideration that EOI and EOD without getting drunk appear to be predicted by different risk factors in childhood and adolescence. Keywords: Adolescents, Alcohol, Intoxication, Drinking, Onset, Predictors

  4. Cost analysis of magnetically controlled growing rods compared with traditional growing rods for early-onset scoliosis in the US: an integrated health care delivery system perspective

    Science.gov (United States)

    Polly, David W; Ackerman, Stacey J; Schneider, Karen; Pawelek, Jeff B; Akbarnia, Behrooz A

    2016-01-01

    Purpose Traditional growing rod (TGR) for early-onset scoliosis (EOS) is effective but requires repeated invasive surgical lengthenings under general anesthesia. Magnetically controlled growing rod (MCGR) is lengthened noninvasively using a hand-held magnetic external remote controller in a physician office; however, the MCGR implant is expensive, and the cumulative cost savings have not been well studied. We compared direct medical costs of MCGR and TGR for EOS from the US integrated health care delivery system perspective. We hypothesized that over time, the MCGR implant cost will be offset by eliminating repeated TGR surgical lengthenings. Methods For both TGR and MCGR, the economic model estimated the cumulative costs for initial implantation, lengthenings, revisions due to device failure, surgical-site infections, device exchanges (at 3.8 years), and final fusion, over a 6-year episode of care. Model parameters were estimated from published literature, a multicenter EOS database of US institutions, and interviews. Costs were discounted at 3.0% annually and represent 2015 US dollars. Results Of 1,000 simulated patients over 6 years, MCGR was associated with an estimated 270 fewer deep surgical-site infections and 197 fewer revisions due to device failure compared with TGR. MCGR was projected to cost an additional $61 per patient over the 6-year episode of care compared with TGR. Sensitivity analyses indicated that the results were sensitive to changes in the percentage of MCGR dual rod use, months between TGR lengthenings, percentage of hospital inpatient (vs outpatient) TGR lengthenings, and MCGR implant cost. Conclusion Cost neutrality of MCGR to TGR was achieved over the 6-year episode of care by eliminating repeated TGR surgical lengthenings. To our knowledge, this is the first cost analysis comparing MCGR to TGR – from the US provider perspective – which demonstrates the efficient provision of care with MCGR. PMID:27695352

  5. Early onset MSI-H colon cancer with MLH1 promoter methylation, is there a genetic predisposition?

    International Nuclear Information System (INIS)

    Roon, Eddy HJ van; Hes, Frederik J; Tops, Carli MJ; Wezel, Tom van; Boer, Judith M; Morreau, Hans; Puijenbroek, Marjo van; Middeldorp, Anneke; Eijk, Ronald van; Meijer, Emile J de; Erasmus, Dianhdra; Wouters, Kim AD; Engeland, Manon van; Oosting, Jan

    2010-01-01

    To investigate the etiology of MLH1 promoter methylation in mismatch repair (MMR) mutation-negative early onset MSI-H colon cancer. As this type of colon cancer is associated with high ages, young patients bearing this type of malignancy are rare and could provide additional insight into the etiology of sporadic MSI-H colon cancer. We studied a set of 46 MSI-H colon tumors cases with MLH1 promoter methylation which was enriched for patients with an age of onset below 50 years (n = 13). Tumors were tested for CIMP marker methylation and mutations linked to methylation: BRAF, KRAS, GADD45A and the MLH1 -93G>A polymorphism. When available, normal colon and leukocyte DNA was tested for GADD45A mutations and germline MLH1 methylation. SNP array analysis was performed on a subset of tumors. We identified two cases (33 and 60 years) with MLH1 germline promoter methylation. BRAF mutations were less frequent in colon cancer patients below 50 years relative to patients above 50 years (p-value: 0.044). CIMP-high was infrequent and related to BRAF mutations in patients below 50 years. In comparison with published controls the G>A polymorphism was associated with our cohort. Although similar distribution of the pathogenic A allele was observed in the patients with an age of onset above and below 50 years, the significance for the association was lost for the group under 50 years. GADD45A sequencing yielded an unclassified variant. Tumors from both age groups showed infrequent copy number changes and loss-of-heterozygosity. Somatic or germline GADD45A mutations did not explain sporadic MSI-H colon cancer. Although germline MLH1 methylation was found in two individuals, locus-specific somatic MLH1 hypermethylation explained the majority of sporadic early onset MSI-H colon cancer cases. Our data do not suggest an intrinsic tendency for CpG island hypermethylation in these early onset MSI-H tumors other than through somatic mutation of BRAF

  6. Early onset MSI-H colon cancer with MLH1 promoter methylation, is there a genetic predisposition?

    Directory of Open Access Journals (Sweden)

    Hes Frederik J

    2010-05-01

    Full Text Available Abstract Background To investigate the etiology of MLH1 promoter methylation in mismatch repair (MMR mutation-negative early onset MSI-H colon cancer. As this type of colon cancer is associated with high ages, young patients bearing this type of malignancy are rare and could provide additional insight into the etiology of sporadic MSI-H colon cancer. Methods We studied a set of 46 MSI-H colon tumors cases with MLH1 promoter methylation which was enriched for patients with an age of onset below 50 years (n = 13. Tumors were tested for CIMP marker methylation and mutations linked to methylation: BRAF, KRAS, GADD45A and the MLH1 -93G>A polymorphism. When available, normal colon and leukocyte DNA was tested for GADD45A mutations and germline MLH1 methylation. SNP array analysis was performed on a subset of tumors. Results We identified two cases (33 and 60 years with MLH1 germline promoter methylation. BRAF mutations were less frequent in colon cancer patients below 50 years relative to patients above 50 years (p-value: 0.044. CIMP-high was infrequent and related to BRAF mutations in patients below 50 years. In comparison with published controls the G>A polymorphism was associated with our cohort. Although similar distribution of the pathogenic A allele was observed in the patients with an age of onset above and below 50 years, the significance for the association was lost for the group under 50 years. GADD45A sequencing yielded an unclassified variant. Tumors from both age groups showed infrequent copy number changes and loss-of-heterozygosity. Conclusion Somatic or germline GADD45A mutations did not explain sporadic MSI-H colon cancer. Although germline MLH1 methylation was found in two individuals, locus-specific somatic MLH1 hypermethylation explained the majority of sporadic early onset MSI-H colon cancer cases. Our data do not suggest an intrinsic tendency for CpG island hypermethylation in these early onset MSI-H tumors other than through

  7. Development of a panel of seven duplex real-time PCR assays for detecting 13 streptococcal superantigens.

    Science.gov (United States)

    Yang, Peng; Peng, Xiaomin; Cui, Shujuan; Shao, Junbin; Zhu, Xuping; Zhang, Daitao; Liang, Huijie; Wang, Quanyi

    2013-07-30

    Streptococcal superantigens (SAgs) are the major virulence factors of infection in humans for group A Streptococcus (GAS) bacteria. A panel consisting of seven duplex real-time PCR assays was developed to simultaneously detect 13 streptococcal SAgs and one internal control which may be important in the control of GAS-mediated diseases. Primer and probe sequences were selected based on the highly conserved region from an alignment of nucleotide sequences of the 13 streptococcal SAgs. The reaction conditions of the duplex real-time PCR were optimized and the specificity of the duplex assays was evaluated using SAg positive strains. The limit of detection of the duplex assays was determined by using 10-fold serial dilutions of the DNA of 13 streptococcal SAgs and compared to a conventional polymerase chain reaction (PCR) method for evaluating the duplex assays sensitivity. Using the duplex assays, we were able to differentiate between 13 SAgs from Streptococcus strains and other non-Streptococcus bacteria without cross-reaction. On the other hand, the limit of detection of the duplex assays was at least one or two log dilutions lower than that of the conventional PCR. The panel was highly specific (100%) and the limit of detection of these duplex groups was at least ten times lower than that obtained by using a conventional PCR method.

  8. The Constellation of Macrovascular Risk Factors in Early Onset T2DM: A Cross-Sectional Study in Xinjiang Province, China

    Directory of Open Access Journals (Sweden)

    Mingchen Zhang

    2018-01-01

    Full Text Available Background. Despite a rapid popular of early onset type 2 diabetes (defined as diagnosis at <40 years old recently, there is a lack of studies on this population in economically undeveloped area. We aimed to investigate the risk factors of macrovascular complications in the early onset T2DM patients in Xinjiang, China. Methods. A cross-sectional survey of 1736 consecutive patients with T2DM was conducted. Macrovascular complications and risk factors were documented. Another nondiabetic population matched with age and sex was as a control group. Logistic regression analysis was performed to obtain odds ratios (OR for macrovascular complications in early and late onset T2DM, respectively. Results. The final analysis consisted of 1036 late onset and 219 early onset T2DM patients. The mean HbA1c in the early onset group was higher than that in the late onset group (9.1 ± 2.4% versus 8.3 ± 2.2%, P=0.039 despite a higher proportion of patients in the early onset group receiving insulin treatment (73.1% versus 58.7%, P<0.001. Compared to the control, early onset patients had higher blood pressure and worse lipid profiles (all P<0.01. More than half of the early onset T2DM patients already had macro- and microvascular complications, despite of their young age (39.5 ± 10.8 and short DM duration (6.6 ± 8.0. In the early onset group, women had a ~3-fold hazard of atherosclerotic plaques compared with men (OR 3.22, 95% CI 1.53–6.78. Conclusions. Patients with early onset T2DM have worse glycemic control and higher burden of atherogenic risk factors. The prevalence of macro- and microvascular complications is astonishingly high in these young adults with T2DM. Moreover, young women with T2DM are more susceptible to cardiovascular complications than their male counterpart.

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

    Science.gov (United States)

    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.

  10. A novel germline POLE mutation causes an early onset cancer prone syndrome mimicking constitutional mismatch repair deficiency.

    Science.gov (United States)

    Wimmer, Katharina; Beilken, Andreas; Nustede, Rainer; Ripperger, Tim; Lamottke, Britta; Ure, Benno; Steinmann, Diana; Reineke-Plaass, Tanja; Lehmann, Ulrich; Zschocke, Johannes; Valle, Laura; Fauth, Christine; Kratz, Christian P

    2017-01-01

    In a 14-year-old boy with polyposis and rectosigmoid carcinoma, we identified a novel POLE germline mutation, p.(Val411Leu), previously found as recurrent somatic mutation in 'ultramutated' sporadic cancers. This is the youngest reported cancer patient with polymerase proofreading-associated polyposis indicating that POLE mutation p.(Val411Leu) may confer a more severe phenotype than previously reported POLE and POLD1 germline mutations. The patient had multiple café-au-lait macules and a pilomatricoma mimicking the clinical phenotype of constitutional mismatch repair deficiency. We hypothesize that these skin features may be common to different types of constitutional DNA repair defects associated with polyposis and early-onset cancer.

  11. The French series of autosomal dominant early onset Alzheimer's disease cases: mutation spectrum and cerebrospinal fluid biomarkers.

    Science.gov (United States)

    Wallon, David; Rousseau, Stéphane; Rovelet-Lecrux, Anne; Quillard-Muraine, Muriel; Guyant-Maréchal, Lucie; Martinaud, Olivier; Pariente, Jérémie; Puel, Michèle; Rollin-Sillaire, Adeline; Pasquier, Florence; Le Ber, Isabelle; Sarazin, Marie; Croisile, Bernard; Boutoleau-Bretonnière, Claire; Thomas-Antérion, Catherine; Paquet, Claire; Moreaud, Olivier; Gabelle, Audrey; Sellal, François; Sauvée, Mathilde; Laquerrière, Annie; Duyckaerts, Charles; Delisle, Marie-Bernadette; Streichenberger, Nathalie; Lannes, Béatrice; Frebourg, Thierry; Hannequin, Didier; Campion, Dominique

    2012-01-01

    We describe 56 novel autosomal dominant early-onset Alzheimer disease (ADEOAD) families with PSEN1, PSEN2, and AβPP mutations or duplications, raising the total of families with mutations on known genes to 111 (74 PSEN1, 8 PSEN2, 16 AβPP, and 13 AβPP duplications) in the French series. In 33 additional families (23% of the series), the genetic determinism remained uncharacterized after this screening. Cerebrospinal fluid (CSF) biomarker levels were obtained for patients of 58 families (42 with known mutations and 16 without genetic characterization). CSF biomarkers profile was consistent with an AD diagnosis in 90% of families carrying mutations on known genes. In families without mutation, CSF biomarkers were consistent with AD diagnosis in 14/16 cases. Overall, these results support further genetic heterogeneity in the determinism of ADEOAD and suggest that other major genes remain to be characterized.

  12. Novel PSEN1 G209A mutation in early-onset Alzheimer dementia supported by structural prediction.

    Science.gov (United States)

    An, Seong Soo A; Bagyinszky, Eva; Kim, Hye Ryoun; Seok, Ju-Won; Shin, Hae-Won; Bae, SeunOh; Kim, SangYun; Youn, Young Chul

    2016-05-20

    Three main genes are described as causative genes for early-onset Alzheimer dementia (EOAD): APP, PSEN1 and PSEN2. We describe a woman with EOAD had a novel PSEN1 mutation. A 54-year-old right-handed woman presented 12-year history of progressive memory decline. She was clinically diagnosed as familial Alzheimer's disease due to a PSEN1 mutation. One of two daughters also has the same mutation, G209A in the TM-IV of PS1 protein. Her mother had unspecified dementia that began at the age of 40s. PolyPhen2 and SIFT prediction suggested that G209A might be a damaging variant with high scores. 3D modeling revealed that G209A exchange could result significant changes in the PS1 protein. We report a case of EOAD having probable novel PSEN1 (G209A) mutation verified with structural prediction.

  13. Cartilage oligomeric matrix protein deficiency promotes early onset and the chronic development of collagen-induced arthritis

    DEFF Research Database (Denmark)

    Geng, Hui; Carlsen, Stefan; Nandakumar, Kutty

    2008-01-01

    ABSTRACT: INTRODUCTION: Cartilage oligomeric matrix protein (COMP) is a homopentameric protein in cartilage. The development of arthritis, like collagen-induced arthritis (CIA), involves cartilage as a target tissue. We have investigated the development of CIA in COMP-deficient mice. METHODS: COMP......-deficient mice in the 129/Sv background were backcrossed for 10 generations against B10.Q mice, which are susceptible to chronic CIA. COMP-deficient and wild-type mice were tested for onset, incidence, and severity of arthritis in both the collagen and collagen antibody-induced arthritis models. Serum anti......-collagen II and anti-COMP antibodies as well as serum COMP levels in arthritic and wild-type mice were measured by enzyme-linked immunosorbent assay. RESULTS: COMP-deficient mice showed a significant early onset and increase in the severity of CIA in the chronic phase, whereas collagen II-antibody titers were...

  14. How Should Clinicians Counsel a Woman with a Strong Family History of Early-Onset Alzheimer's Disease about Her Pregnancy?

    Science.gov (United States)

    Mapes, Marianna V; O'Brien, Barbara M; King, Louise P

    2017-07-01

    Counseling patients regarding the benefits, harms, and dilemmas of genetic testing is one of the greatest ethical challenges facing reproductive medicine today. With or without test results, clinicians grapple with how to communicate potential genetic risks as patients weigh their reproductive options. Here, we consider a case of a woman with a strong family history of early-onset Alzheimer's disease (EOAD). She is early in her pregnancy and unsure about learning her own genetic status. We address the ethical ramifications of each of her options, which include genetic testing, genetic counseling, and termination versus continuation of the pregnancy. Our analysis foregrounds clinicians' role in helping to ensure autonomous decision making as the patient reflects on these clinical options in light of her goals and values. © 2017 American Medical Association. All Rights Reserved.

  15. Bubble CPAP versus ventilator CPAP in preterm neonates with early onset respiratory distress--a randomized controlled trial.

    Science.gov (United States)

    Tagare, Amit; Kadam, Sandeep; Vaidya, Umesh; Pandit, Anand; Patole, Sanjay

    2013-04-01

    Bubble continuous positive airway pressure (BCPAP) is a low cost nasal CPAP delivery system with potential benefits to developing nations. To compare the efficacy and safety of BCPAP with ventilator-derived CPAP (VCPAP) in preterm neonates with respiratory distress. In a randomized controlled trial, preterm neonates with Silverman-Anderson score ≥ 4 and oxygen requirement >30% within first 6 h of life were randomly allocated to BCPAP or VCPAP. Proportion of neonates with success or failure was compared. In all, 47 of 57 (82.5%) neonates from BCPAP group and 36 of 57 (63.2%) neonates from the VCPAP group completed CPAP successfully (p = 0.03). Neonates who failed CPAP had higher Silverman-Anderson score (p neonates with early onset respiratory distress, with comparable safety.

  16. Patterns and correlates of expressed emotion, perceived criticism, and rearing style in first admitted early-onset schizophrenia spectrum disorders.

    Science.gov (United States)

    von Polier, Georg G; Meng, Heiner; Lambert, Martin; Strauss, Monika; Zarotti, Gianni; Karle, Michael; Dubois, Reinmar; Stark, Fritz-Michael; Neidhart, Sibylle; Zollinger, Ruedi; Bürgin, Dieter; Felder, Wilhelm; Resch, Franz; Koch, Eginhard; Schulte-Markwort, Michael; Schimmelmann, Benno G

    2014-11-01

    The aim of this study was to assess patterns and correlates of family variables in 31 adolescents treated for their first episode of a schizophrenia spectrum disorder (early-onset schizophrenia [EOS]). Expressed emotion, perceived criticism, and rearing style were assessed. Potential correlates were patient psychopathology, premorbid adjustment, illness duration, quality of life (QoL), sociodemographic variables, patient and caregiver "illness concept," and caregiver personality traits and support. Families were rated as critical more frequently by patients than raters (55% vs. 13%). Perceived criticism was associated with worse QoL in relationship with parents and peers. An adverse rearing style was associated with a negative illness concept in patients, particularly with less trust in their physician. Future research should examine perceived criticism as a predictor of relapse and indicator of adolescents with EOS who need extended support and treatment. Rearing style should be carefully observed because of its link with patients' illness concept and, potentially, to service engagement and medication adherence.

  17. A novel BRCA2 in frame deletion in a Tunisian woman with early onset sporadic breast cancer.

    Science.gov (United States)

    Hadiji-Abbes, N; Trifa, F; Choura, M; Khabir, A; Sellami-Boudawara, T; Frikha, M; Daoud, J; Mokdad-Gargouri, R

    2015-09-01

    Breast cancer is increasing among young women in Tunisia. Germline mutations in the BRCA1/2 genes are associated with a high risk for breast cancer development. However, the true contribution of BRCA1/2 mutation in sporadic breast cancer is not well documented. Our aim is to identify the BRCA2 mutation spectrum in Tunisian young women with breast cancer. Screening the BRCA2 gene was performed using DHPLC, DNA sequencing and PCR-RFLP. We identified, in a woman diagnosed with early onset breast cancer, and without family history, a novel in frame deletion 5456delGTAGCA in the exon 11 of the BRCA2 gene which causes a loss of two residues Ser1743-Ser1744. The absence of this deletion in the patients' parents suggests that it is a de novo variant. Furthermore, we screened 108 sporadic cases, 50 familial cases, and 60 controls for the identified del6bp using PCR-RFLP. None of them carried this deletion suggesting that this variant is not a benign polymorphism and probably rare in our population. With regards to the position of the Ser1743-1744 in the BRCT domain, sequence alignment revealed that the Ser1743 is conserved among several species, which may reflect its importance in the BRCA2 function. A modeling of the wild-type and mutated BRC5-BRC6 domain revealed that the deletion of the 2 Serine residues might affect the structure of this BRCA2 domain. A novel in frame deletion 5456del6bp in BRCA2 gene was identified in an early onset woman with breast cancer and without family history. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  18. Lost opportunities to prevent early onset type 2 diabetes mellitus after a pregnancy complicated by gestational diabetes.

    Science.gov (United States)

    Bernstein, Judith A; McCloskey, Lois; Gebel, Christina M; Iverson, Ronald E; Lee-Parritz, Aviva

    2016-01-01

    Gestational diabetes mellitus (GDM) greatly increases the risk of developing diabetes in the decade after delivery, but few women receive appropriately timed postpartum glucose testing (PPGT) or a referral to primary care (PC) for continued monitoring. This qualitative study was designed to identify barriers and facilitators to testing and referral from patient and providers' perspectives. We interviewed patients and clinicians in depth about knowledge, values, priorities, challenges, and recommendations for increasing PPGT rates and PC linkage. Interviews were coded with NVIVO data analysis software, and analyzed using an implementation science framework. Women reported motivation to address GDM for the health of the fetus. Most women did not anticipate future diabetes for themselves, and focused on delivery outcomes rather than future health risks. Patients sought and received reassurance from clinicians, and were unlikely to discuss early onset following GDM or preventive measures. PPGT barriers described by patients included provider not mentioning the test or setting it up, transportation difficulties, work responsibilities, fatigue, concerns about fasting while breastfeeding, and timing of the test after discharge from obstetrics, and no referral to PC for follow-up. Practitioners described limited communication among multiple care providers during pregnancy and delivery, systems issues, and separation of obstetrics from PC. Patients' barriers to PPGT included low motivation for self-care, structural obstacles, and competing priorities. Providers reported the need to balance risk with reassurance, and identified systems failures related to test timing, limitations of electronic medical record systems (EMR), lack of referrals to PC, and inadequate communication between specialties. Prevention of early onset has great potential for medical cost savings and improvements in quality of life.

  19. Multimodel assessment of BRCA1 mutations in Taiwanese (ethnic Chinese) women with early-onset, bilateral or familial breast cancer.

    Science.gov (United States)

    Kuo, Wen-Hong; Lin, Po-Han; Huang, Ai-Chu; Chien, Yin-Hsiu; Liu, Tsang-Pai; Lu, Yen-Shen; Bai, Li-Yuan; Sargeant, Aaron M; Lin, Ching-Hung; Cheng, Ann-Lii; Hsieh, Fon-Jou; Hwu, Wuh-Liang; Chang, King-Jen

    2012-02-01

    Although evidence suggests an importance of genetic factors in the development of breast cancer in Taiwanese (ethnic Chinese) women, including a high incidence of early-onset and secondary contralateral breast cancer, a major breast cancer predisposition gene, BRCA1, has not been well studied in this population. In fact, the carcinogenic impacts of many genetic variants of BRCA1 are unknown and classified as variants of uncertain significance (VUS). It is therefore important to establish a method to characterize the BRCA1 VUSs and understand their role in Taiwanese breast cancer patients. Accordingly, we developed a multimodel assessment strategy consisting of a prescreening portion and a validated functional assay to study breast cancer patients with early-onset, bilateral or familial breast cancer. We found germ-line BRCA1 mutations in 11.1% of our cohort and identified one novel missense mutation, c.5191C>A. Two genetic variants were initially classified as VUSs (c.1155C>T and c.5191C>A). c.1155C>T is not predicted to be deleterious in the prescreening portion of our assessment strategy. c.5191C>A, on the other hand, causes p.T1691K, which is predicted to have high deleterious probability because of significant structural alteration, a high deleterious score in the predictive programs and, clinically, triple negative characteristics in breast tumors. This mutant is confirmed by transcription activation and yeast growth-inhibition assays. In conclusion, we show as high a prevalence of germ-line BRCA1 mutation in high-risk Taiwanese patients as in Caucasians and demonstrate a useful strategy for studying BRCA1 VUSs.

  20. α-Synuclein deficiency and efferent nerve degeneration in the mouse cochlea: a possible cause of early-onset presbycusis.

    Science.gov (United States)

    Park, S N; Back, S A; Choung, Y H; Kim, H L; Akil, O; Lustig, L R; Park, K H; Yeo, S W

    2011-11-01

    Efferent nerves under the outer hair cells (OHCs) play a role in the protection of these cells from loud stimuli. Previously, we showed that cochlear α-synuclein expression is localized to efferent auditory synapses at the base of the OHCs. To prove our hypothesis that α-synuclein deficiency and efferent auditory deficit might be a cause of hearing loss, we compared the morphology of efferent nerve endings and α-synuclein expression within the cochleae of two mouse models of presbycusis. Comparative animal study of presbycusis. The C57BL/6J(C57) mouse strain, a well-known model of early-onset hearing loss, and the CBA mouse strain, a model of relatively late-onset hearing loss, were examined. Auditory brainstem responses and distortion product otoacoustic emissions were recorded, and cochlear morphology with efferent nerve ending was compared. Western blotting was used to examine α-synuclein expression in the cochlea. Compared with CBA mice, C57 mice showed earlier onset high-frequency hearing loss and decreased function in OHCs, especially within high-frequency regions. C57 mice demonstrated more severe pathologic changes within the cochlea, particularly within the basal turn, than CBA mice of the same age. Weaker α-synuclein and synaptophysin expression in the efferent nerve endings and cochlear homogenates in C57 mice was observed. Our results support the hypothesis that efferent nerve degeneration, possibly due to differential α-synuclein expression, is a potential cause of early-onset presbycusis. Further studies at the cellular level are necessary to verify our results. Copyright © 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

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

    Science.gov (United States)

    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.

  2. 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

  3. 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.

  4. 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.

  5. Do rapid BMI growth in childhood and early-onset obesity offer cardiometabolic protection to obese adults in mid-life?

    DEFF Research Database (Denmark)

    Howe, Laura D; Zimmermann, Esther; Weiss, Ram

    2014-01-01

    BMI growth (7-13 years) using a multilevel model. Early-onset obesity was defined as obesity at examination for national service. OUTCOME MEASUREMENT: We defined metabolic health at the mid-life clinic as non-fasting serum cholesterol fasting glucose ...OBJECTIVE: Some obese individuals have no cardiometabolic abnormalities; they are 'metabolically healthy, but obese' (MHO). Similarly, some non-obese individuals have cardiometabolic abnormalities, that is, 'metabolically at risk, normal weight' (MANW). Previous studies have suggested that early......-onset obesity may be associated with MHO. We aimed to assess whether body mass index (BMI) in childhood and early-onset obesity are associated with MHO. SETTING: General population longitudinal cohort study, Denmark. PARTICIPANTS: From 362 200 young men (mean age 20) examined for Danish national service between...

  6. Linkage of familial Alzheimer disease to chromosome 14 in two large early-onset pedigrees: effects of marker allele frequencies on lod scores.

    Science.gov (United States)

    Nechiporuk, A; Fain, P; Kort, E; Nee, L E; Frommelt, E; Polinsky, R J; Korenberg, J R; Pulst, S M

    1993-05-01

    Alzheimer disease (AD) is a devastating neurodegenerative disease leading to global dementia. In addition to sporadic forms of AD, familial forms (FAD) have been recognized. Mutations in the amyloid precursor protein (APP) gene on chromosome (CHR) 21 have been shown to cause early-onset AD in a small number of pedigrees. Recently, linkage to markers on CHR 14 has been established in several early-onset FAD pedigrees. We now report lod scores for CHR 14 markers in two large early-onset FAD pedigrees. Pairwise linkage analysis suggested that in these pedigrees the mutation is tightly linked to the loci D14S43 and D14S53. However, assumptions regarding marker allele frequencies had a major and often unpredictable effect on calculated lod scores. Therefore, caution needs to be exercised when single pedigrees are analyzed with marker allele frequencies determined from the literature or from a pool of spouses.

  7. Proteomics mapping of cord blood identifies haptoglobin "switch-on" pattern as biomarker of early-onset neonatal sepsis in preterm newborns.

    Science.gov (United States)

    Buhimschi, Catalin S; Bhandari, Vineet; Dulay, Antonette T; Nayeri, Unzila A; Abdel-Razeq, Sonya S; Pettker, Christian M; Thung, Stephen; Zhao, Guomao; Han, Yiping W; Bizzarro, Matthew; Buhimschi, Irina A

    2011-01-01

    Intra-amniotic infection and/or inflammation (IAI) are important causes of preterm birth and early-onset neonatal sepsis (EONS). A prompt and accurate diagnosis of EONS is critical for improved neonatal outcomes. We sought to explore the cord blood proteome and identify biomarkers and functional protein networks characterizing EONS in preterm newborns. We studied a prospective cohort of 180 premature newborns delivered May 2004-September 2009. A proteomics discovery phase employing two-dimensional differential gel electrophoresis (2D-DIGE) and mass spectrometry identified 19 differentially-expressed proteins in cord blood of newborns with culture-confirmed EONS (n = 3) versus GA-matched controls (n = 3). Ontological classifications of the proteins included transfer/carrier, immunity/defense, protease/extracellular matrix. The 1(st)-level external validation conducted in the remaining 174 samples confirmed elevated haptoglobin and haptoglobin-related protein immunoreactivity (Hp&HpRP) in newborns with EONS (presumed and culture-confirmed) independent of GA at birth and birthweight (PLCA) was further used for unbiased classification of all 180 cases based on probability of "antenatal IAI exposure" as latent variable. This was then subjected to 2(nd)-level validation against indicators of adverse short-term neonatal outcome. The optimal LCA algorithm combined Hp&HpRP switch pattern (most input), interleukin-6 and neonatal hematological indices yielding two non-overlapping newborn clusters with low (≤20%) versus high (≥70%) probability of IAI exposure. This approach reclassified ∼30% of clinical EONS diagnoses lowering the number needed to harm and increasing the odds ratios for several adverse outcomes including intra-ventricular hemorrhage. Antenatal exposure to IAI results in precocious switch-on of Hp&HpRP expression. As EONS biomarker, cord blood Hp&HpRP has potential to improve the selection of newborns for prompt and targeted treatment at birth.

  8. Proteomics Mapping of Cord Blood Identifies Haptoglobin “Switch-On” Pattern as Biomarker of Early-Onset Neonatal Sepsis in Preterm Newborns

    Science.gov (United States)

    Buhimschi, Catalin S.; Bhandari, Vineet; Dulay, Antonette T.; Nayeri, Unzila A.; Abdel-Razeq, Sonya S.; Pettker, Christian M.; Thung, Stephen; Zhao, Guomao; Han, Yiping W.; Bizzarro, Matthew; Buhimschi, Irina A.

    2011-01-01

    Background Intra-amniotic infection and/or inflammation (IAI) are important causes of preterm birth and early-onset neonatal sepsis (EONS). A prompt and accurate diagnosis of EONS is critical for improved neonatal outcomes. We sought to explore the cord blood proteome and identify biomarkers and functional protein networks characterizing EONS in preterm newborns. Methodology/Principal Findings We studied a prospective cohort of 180 premature newborns delivered May 2004-September 2009. A proteomics discovery phase employing two-dimensional differential gel electrophoresis (2D-DIGE) and mass spectrometry identified 19 differentially-expressed proteins in cord blood of newborns with culture-confirmed EONS (n = 3) versus GA-matched controls (n = 3). Ontological classifications of the proteins included transfer/carrier, immunity/defense, protease/extracellular matrix. The 1st-level external validation conducted in the remaining 174 samples confirmed elevated haptoglobin and haptoglobin-related protein immunoreactivity (Hp&HpRP) in newborns with EONS (presumed and culture-confirmed) independent of GA at birth and birthweight (PLCA) was further used for unbiased classification of all 180 cases based on probability of “antenatal IAI exposure” as latent variable. This was then subjected to 2nd-level validation against indicators of adverse short-term neonatal outcome. The optimal LCA algorithm combined Hp&HpRP switch pattern (most input), interleukin-6 and neonatal hematological indices yielding two non-overlapping newborn clusters with low (≤20%) versus high (≥70%) probability of IAI exposure. This approach reclassified ∼30% of clinical EONS diagnoses lowering the number needed to harm and increasing the odds ratios for several adverse outcomes including intra-ventricular hemorrhage. Conclusions/Significance Antenatal exposure to IAI results in precocious switch-on of Hp&HpRP expression. As EONS biomarker, cord blood Hp&HpRP has potential to improve the

  9. A glimpse of streptococcal toxic shock syndrome from comparative genomics of S. suis 2 Chinese isolates

    DEFF Research Database (Denmark)

    Chen, Chen; Tang, Jiaqi; Dong, Wei

    2007-01-01

    shock syndrome (STSS), which was originally associated with Streptococcus pyogenes (GAS) in Streptococci. However, the molecular mechanisms underlying STSS are poorly understood. METHODS AND FINDINGS: To elucidate the genetic determinants of STSS caused by SS2, whole genome sequencing of 3 different......BACKGROUND: Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen, causing more than 200 cases of severe human infection worldwide, with the hallmarks of meningitis, septicemia, arthritis, etc. Very recently, SS2 has been recognized as an etiological agent for streptococcal toxic...

  10. Streptococcal Subdural Empyema as a Complication of Varicella

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2005-01-01

    Full Text Available A 3-month-old male infant who presented with a group A streptococcal subdural empyema on day 5 of a varicella skin rash is reported from the University of British Columbia, Vancouver, BC, Canada.

  11. Predictors of suicide attempt in early-onset, first-episode psychoses: a longitudinal 24-month follow-up study.

    Science.gov (United States)

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

    2013-01-01

    To study the prevalence of suicide attempts and factors associated with risk for suicide during the first episode of psychosis, and to identify early predictors of suicide attempts over a 24-month follow-up period in an early-onset, first-episode psychosis cohort. 110 subjects in their first episode of psychosis aged between 9 and 17 years were assessed by using the DSM-IV diagnostic interview Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version and a battery of clinical instruments at baseline and at 12 and 24 months. Patients were enrolled in the study from March 2003 through November 2005. Suicide attempts and level of suicidality at each assessment were evaluated by using the Clinical Global Impression for Severity of Suicidality and the Hamilton Depression Rating Scale. Subjects were classified as being at high, low, or no risk of suicide, depending on their scores on certain items of these scales. Clinical associations between the outcome measures high risk for suicide during acute episode and suicide attempts during follow-up were investigated by 2 sets of logistic regression analyses. The 24-month prevalence of suicide attempters was 12.4%. History of suicide attempts prior to psychotic episode (OR = 20.13; 95% CI, 1.83-220.55; P = .01), severe depressive symptoms (OR = 8.78; 95% CI, 1.15-67.11; P = .003), and antidepressant treatment (OR = 15.56; 95% CI, 2.66-90.86; P = .002) were associated with being classified as high suicide risk at baseline. The categorization of high suicide risk at baseline predicted suicide attempts during follow-up (OR = 81.66; 95% CI, 11.61-574.35; P = .000). Suicide is a major concern in early-onset first-episode psychosis. Suicidal behavior and depressive symptoms at psychosis onset are important signs to be aware of to prevent suicide attempts during the early period after first-episode psychosis. © Copyright 2013 Physicians Postgraduate Press, Inc.

  12. Invasive Group A streptococcal disease in Ireland, 2004 to 2010.

    LENUS (Irish Health Repository)

    Martin, J

    2011-01-01

    Invasive group A streptococcal infections (iGAS) are a major clinical and public health challenge. iGAS is a notifiable disease in Ireland since 2004. The aim of this paper is to describe the epidemiology of iGAS in Ireland for the first time over the seven-year period from 2004 to 2010. The Irish national electronic infectious disease reporting system was used by laboratories to enter the source of iGAS isolates, and by departments of public health to enter clinical and epidemiological details. We extracted and analysed data from 1 January 2004 to 31 December 2010. Over the study period, 400 iGAS cases were notified. The annual incidence of iGAS doubled, from 0.8 per 100,000 population in 2004 to 1.6 in 2008, and then remained the same in 2009 and 2010. The reported average annual incidence rates were highest among children up to five years of age (2.3\\/100,000) and adults aged over 60 years (3.2\\/100,000). The most common risk factors associated with iGAS were skin lesions or wounds. Of the 174 people for whom clinical syndrome information was available, 28 (16%) cases presented with streptococcal toxic shock syndrome and 19 (11%) with necrotising fasciitis. Of the 141 cases for whom seven-day outcomes were recorded, 11 people died with iGAS identified as the main cause of death (seven-day case fatality rate 8%). The notification rate of iGAS in Ireland was lower than that reported in the United Kingdom, Nordic countries and North America but higher than southern and eastern European countries. The reasons for lower notification rates in Ireland compared with other countries may be due to a real difference in incidence, possibly due to prescribing practices, or due to artefacts resulting from the specific Irish case definition and\\/or low reporting in the early stages of a new surveillance system. iGAS disease remains an uncommon but potentially severe disease in Ireland. Ongoing surveillance is required in order to undertake appropriate control measures and

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

    Science.gov (United States)

    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.

  14. Mutational spectrum of CDKL5 in early-onset encephalopathies: a study of a large collection of French patients and review of the literature.

    Science.gov (United States)

    Nemos, C; Lambert, L; Giuliano, F; Doray, B; Roubertie, A; Goldenberg, A; Delobel, B; Layet, V; N'guyen, M A; Saunier, A; Verneau, F; Jonveaux, P; Philippe, C

    2009-10-01

    The CDKL5 gene has been implicated in the molecular etiology of early-onset intractable seizures with infantile spasms (IS), severe hypotonia and atypical Rett syndrome (RTT) features. So far, 48 deleterious alleles have been reported in the literature. We screened the CDKL5 gene in a cohort of 177 patients with early-onset seizures, including 30 men and 10 girls with Aicardi syndrome. The screening was negative for all men as well as for women with Aicardi syndrome, excluding the CDKL5 gene as a candidate for this neurodevelopmental disorder. We report 11 additional de novo mutations in CDKL5 in female patients. For the first time, the MLPA approach allowed the identification of a partial deletion encompassing the promoter and the first two exons of CDKL5. The 10-point mutations consist of five missenses (with recurrent amino acid changes at p.Ala40 and p.Arg178), four splicing variants and a 1-base pair duplication. We present a review of all mutated alleles published in the literature. In our study, the overall frequency of mutations in CDKL5 in women with early-onset seizures is around 8.6%, a result comparable with previous reports. Noteworthy, the CDKL5 mutation rate is high (28%) in women with early-onset seizures and IS.

  15. Perinatal morbidity and mortality in early-onset fetal growth restriction : cohort outcomes of the trial of randomized umbilical and fetal flow in Europe (TRUFFLE)

    NARCIS (Netherlands)

    Lees, C.; Marlow, N.; Arabin, B.; Bilardo, C. M.; Brezinka, C.; Derks, J. B.; Duvekot, J.; Frusca, T.; Diemert, A.; Ferrazzi, E.; Ganzevoort, W.; Hecher, K.; Martinelli, P.; Ostermayer, E.; Papageorghiou, A. T.; Schlembach, D.; Schneider, K. T. M.; Thilaganathan, B.; Todros, T.; van Wassenaer-Leemhuis, A.; Valcamonico, A.; Visser, G. H. A.; Wolf, H.

    2013-01-01

    ObjectivesFew data exist for counseling and perinatal management of women after an antenatal diagnosis of early-onset fetal growth restriction. Yet, the consequences of preterm delivery and its attendant morbidity for both mother and baby are far reaching. The objective of this study was to describe

  16. First de novo KCND3 mutation causes severe Kv4.3 channel dysfunction leading to early onset cerebellar ataxia, intellectual disability, oral apraxia and epilepsy

    NARCIS (Netherlands)

    Smets, Katrien; Duarri, Anna; Deconinck, Tine; Ceulemans, Berten; van de Warrenburg, Bart P.; Zuechner, Stephan; Gonzalez, Michael Anthony; Schuele, Rebecca; Synofzik, Matthis; Van der Aa, Nathalie; De Jonghe, Peter; Verbeek, Dineke S.; Baets, Jonathan

    2015-01-01

    Background: Identification of the first de novo mutation in potassium voltage-gated channel, shal-related subfamily, member 3 (KCND3) in a patient with complex early onset cerebellar ataxia in order to expand the genetic and phenotypic spectrum. Methods: Whole exome sequencing in a cerebellar ataxia

  17. Evolutionary paths of streptococcal and staphylococcal superantigens

    Directory of Open Access Journals (Sweden)

    Okumura Kayo

    2012-08-01

    Full Text Available Abstract Background Streptococcus pyogenes (GAS harbors several superantigens (SAgs in the prophage region of its genome, although speG and smez are not located in this region. The diversity of SAgs is thought to arise during horizontal transfer, but their evolutionary pathways have not yet been determined. We recently completed sequencing the entire genome of S. dysgalactiae subsp. equisimilis (SDSE, the closest relative of GAS. Although speG is the only SAg gene of SDSE, speG was present in only 50% of clinical SDSE strains and smez in none. In this study, we analyzed the evolutionary paths of streptococcal and staphylococcal SAgs. Results We compared the sequences of the 12–60 kb speG regions of nine SDSE strains, five speG+ and four speG–. We found that the synteny of this region was highly conserved, whether or not the speG gene was present. Synteny analyses based on genome-wide comparisons of GAS and SDSE indicated that speG is the direct descendant of a common ancestor of streptococcal SAgs, whereas smez was deleted from SDSE after SDSE and GAS split from a common ancestor. Cumulative nucleotide skew analysis of SDSE genomes suggested that speG was located outside segments of steeper slopes than the stable region in the genome, whereas the region flanking smez was unstable, as expected from the results of GAS. We also detected a previously undescribed staphylococcal SAg gene, selW, and a staphylococcal SAg -like gene, ssl, in the core genomes of all Staphylococcus aureus strains sequenced. Amino acid substitution analyses, based on dN/dS window analysis of the products encoded by speG, selW and ssl suggested that all three genes have been subjected to strong positive selection. Evolutionary analysis based on the Bayesian Markov chain Monte Carlo method showed that each clade included at least one direct descendant. Conclusions Our findings reveal a plausible model for the comprehensive evolutionary pathway of streptococcal and

  18. Processing speed and executive functions predict real-world everyday living skills in adolescents with early-onset schizophrenia.

    Science.gov (United States)

    Puig, O; Penadés, R; Baeza, I; Sánchez-Gistau, V; De la Serna, E; Fonrodona, L; Andrés-Perpiñá, S; Bernardo, M; Castro-Fornieles, J

    2012-06-01

    Cognition and clinical variables are known to be among the most predictive factors of real-world social functioning and daily living skills in adult-onset schizophrenia. Fewer studies have focused on their impact in adolescents with early-onset schizophrenia (EOS). The aim of this study is to examine the relationships and the predictive value of cognition and clinical variables on real-world daily living skills in a sample of adolescents with EOS. Cognitive, clinical and real-world everyday living skills measures were administered to 45 clinically and pharmacologically stabilized adolescent outpatients with EOS and 45 healthy control subjects matched by age and sex. Multi-variant analyses to compare cognitive and real-world functioning profiles between patients and controls and regression analysis to identify predictors of real-world functioning scores in patients were used. Adolescents with EOS showed a generalized cognitive and real-world daily living skills dysfunction. Several cognitive and clinical variables significantly correlated with real-world daily living skills functioning but only the processing speed and executive functions emerged as independent predictors of everyday living skills scores, explaining 25.1% of the variance. Slowness in processing information and executive dysfunction showed a significant impact on real-world daily living skills in EOS, independently from clinical symptoms and other cognitive variables. Nevertheless, much of the variance in the daily living skills measure remained unaccounted for, suggesting that other factors were involved as well in this young population.

  19. Early-onset severe hereditary sensory and autonomic neuropathy type 1 with S331F SPTLC1 mutation.

    Science.gov (United States)

    Suh, Bum Chun; Hong, Young Bin; Nakhro, Khriezhanuo; Nam, Soo Hyun; Chung, Ki Wha; Choi, Byung-Ok

    2014-02-01

    Hereditary sensory and autonomic neuropathy type I (HSAN I) is an autosomal dominant disease characterized by prominent sensory impairment, resulting in foot ulcers or amputations and has a juvenile to adult onset. The major underlying causes of HSAN I are mutations in SPTLC1, which encodes the first subunit of serine palmitoyltransferase (SPT). To date, there have been no reports with regard to an HSAN patient of Korean origin. In this report we discussed an HSAN I patient with a missense mutation in SPTLC1 (c.992C>T: p.S331F). The patient had noticed frequent falls, lower leg weakness and hand tremors at age five. The patient also presented with foot ulcers, muscle hypotrophy, cataracts, hoarseness, vocal cord palsy and respiratory difficulties and succumbed to the condition at the age of 28 years. In accordance with previous reports, a mutation in Ser331 in the present patient was associated with early-onset and a severe phenotype. Therefore, Ser331 in SPTLC1 is a crucial amino acid, which characterizes the HSAN I phenotype.

  20. Two novel mutations in thymidine kinase-2 cause early onset fatal encephalomyopathy and severe mtDNA depletion.

    Science.gov (United States)

    Lesko, Nicole; Naess, Karin; Wibom, Rolf; Solaroli, Nicola; Nennesmo, Inger; von Döbeln, Ulrika; Karlsson, Anna; Larsson, Nils-Göran

    2010-03-01

    Deficiency of thymidine kinase-2 (TK2) has been described in children with early onset fatal skeletal myopathy. TK2 is a mitochondrial deoxyribonucleoside kinase required for the phosphorylation of deoxycytidine and deoxythymidine and hence is vital for the maintenance of a balanced mitochondrial dNTP pool in post-mitotic tissues. We describe a patient with two novel TK2 mutations, which caused disease onset shortly after birth and death at the age of three months. One mutation (219insCG) generated an early stop codon, thus preventing the synthesis of a functional protein. The second mutation (R130W) resulted in an amino acid substitution, which caused a severe reduction (TK2 enzyme activity. These two novel TK2 mutations cause an extremely severe phenotype with overwhelming central nervous system symptoms not commonly seen in patients with TK2-deficiency. We conclude that the severe clinical presentation in this patient was due to a virtual lack of mitochondrial TK2 activity. Copyright 2009 Elsevier B.V. All rights reserved.

  1. Changes in erythrocyte insulin receptors in normal dogs and keeshond dogs with inheritable, early onset, insulin dependent diabetes mellitus

    International Nuclear Information System (INIS)

    Klaassen, J.K.

    1986-01-01

    Validation of a procedure to evaluate insulin receptors on erythrocytes (RBC-IR) in dogs is described. The specific binding of ( 125 I)iodoinsulin to RBC-IR of normal dogs is significantly greater than binding in keeshonds with an inheritable form of early onset diabetes mellitus. This decreased binding was due to a significant decrease in RBC-IR affinity in the diabetic keeshonds. To determine the effect on RBC-IR, normal dogs were treated with either dexamethasone (0.1 mg/kg) or prednisone (0.3 mg/kg) for 10 days: concentrations of plasma cortisol, glucose, and insulin, plus binding characteristics of RBC-IR were determined. In the dexamethasone treated group, plasma glucose concentrations were elevated significantly by day 6 and continued through day 10. Insulin concentrations were elevated significantly by day 3 and remained elevated through day 10. In the prednisone treated group, glucose concentrations were elevated significantly by day 3, while insulin concentrations were elevated significantly by day 8. Maximum binding of RBC-IR was unaffected by prednisone and neither affinities nor receptor numbers were significantly different from day 1. No changes in plasma cortisol concentration were seen. Diabetic keeshonds on daily insulin treatment were removed from exogenous insulin therapy for 48 hours. Significant increases in glucose concentrations were observed, but no significant changes in cortisol, insulin, average receptor binding affinity, or RBC-IR number per cell occurred

  2. The relationship between childhood conduct disorder and adult antisocial behavior is partially mediated by early-onset alcohol abuse.

    Science.gov (United States)

    Khalifa, Najat; Duggan, Conor; Howard, Rick; Lumsden, John

    2012-10-01

    Early-onset alcohol abuse (EOAA) was previously found to both mediate and moderate the effect of childhood conduct disorder (CD) on adult antisocial behavior (ASB) in an American community sample of young adults (Howard, R., Finn, P. R., Gallagher, J., & Jose, P. (2011). Adolescent-onset alcohol abuse exacerbates the influence of childhood conduct disorder on late adolescent and early adult antisocial behavior. Journal of Forensic Psychiatry and Psychology. Advance online publication. doi:10.1080/14789949.2011.641996). This study tested whether this result would generalize to a British forensic sample comprising 100 male forensic patients with confirmed personality disorder. Results confirmed that those in whom EOAA co-occurred with CD showed the highest level of personality pathology, particularly Cluster B traits and antisocial/borderline comorbidity. Those with co-occurring CD with EOAA, compared with those showing only CD, showed more violence in their criminal history and greater recreational drug use. Regression analysis showed that both EOAA and CD predicted adult ASB when covariates were controlled. Further analysis showed that EOAA significantly mediated but did not moderate the effect of CD on ASB. The failure to demonstrate an exacerbating effect of EOAA on the relationship between CD and ASB likely reflects the high prevalence of CD in this forensic sample. Some implications of these findings are discussed. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

  3. Exome Sequencing Identified a Recessive RDH12 Mutation in a Family with Severe Early-Onset Retinitis Pigmentosa

    Directory of Open Access Journals (Sweden)

    Bo Gong

    2015-01-01

    Full Text Available Retinitis pigmentosa (RP is the most important hereditary retinal disease caused by progressive degeneration of the photoreceptor cells. This study is to identify gene mutations responsible for autosomal recessive retinitis pigmentosa (arRP in a Chinese family using next-generation sequencing technology. A Chinese family with 7 members including two individuals affected with severe early-onset RP was studied. All patients underwent a complete ophthalmic examination. Exome sequencing was performed on a single RP patient (the proband of this family and direct Sanger sequencing on other family members and normal controls was followed to confirm the causal mutations. A homozygous mutation c.437T

  4. BRCA1 and BRCA2 germline mutations in Malaysian women with early-onset breast cancer without a family history.

    Directory of Open Access Journals (Sweden)

    Gaik Theng Toh

    Full Text Available BACKGROUND: In Asia, breast cancer is characterised by an early age of onset: In Malaysia, approximately 50% of cases occur in women under the age of 50 years. A proportion of these cases may be attributable, at least in part, to genetic components, but to date, the contribution of genetic components to breast cancer in many of Malaysia's ethnic groups has not been well-characterised. METHODOLOGY: Given that hereditary breast carcinoma is primarily due to germline mutations in one of two breast cancer susceptibility genes, BRCA1 and BRCA2, we have characterised the spectrum of BRCA mutations in a cohort of 37 individuals with early-onset disease (

  5. Early-onset seizures due to mosaic exonic deletions of CDKL5 in a male and two females.

    Science.gov (United States)

    Bartnik, Magdalena; Derwińska, Katarzyna; Gos, Monika; Obersztyn, Ewa; Kołodziejska, Katarzyna E; Erez, Ayelet; Szpecht-Potocka, Agnieszka; Fang, Ping; Terczyńska, Iwona; Mierzewska, Hanna; Lohr, Naomi J; Bellus, Gary A; Reimschisel, Tyler; Bocian, Ewa; Mazurczak, Tadeusz; Cheung, Sau Wai; Stankiewicz, Paweł

    2011-05-01

    Mutations in the CDKL5 gene have been associated with an X-linked dominant early infantile epileptic encephalopathy-2. The clinical presentation is usually of severe encephalopathy with refractory seizures and Rett syndrome (RTT)-like phenotype. We attempted to assess the role of mosaic intragenic copy number variation in CDKL5. We have used comparative genomic hybridization with a custom-designed clinical oligonucleotide array targeting exons of selected disease and candidate genes, including CDKL5. We have identified mosaic exonic deletions of CDKL5 in one male and two females with developmental delay and medically intractable seizures. These three mosaic changes represent 60% of all deletions detected in 12,000 patients analyzed by array comparative genomic hybridization and involving the exonic portion of CDKL5. We report the first case of an exonic deletion of CDKL5 in a male and emphasize the importance of underappreciated mosaic exonic copy number variation in patients with early-onset seizures and RTT-like features of both genders.

  6. The When and Where of Working Memory Dysfunction in Early-Onset Schizophrenia-A Functional Magnetic Resonance Imaging Study.

    Science.gov (United States)

    Bittner, Robert A; Linden, David E J; Roebroeck, Alard; Härtling, Fabian; Rotarska-Jagiela, Anna; Maurer, Konrad; Goebel, Rainer; Singer, Wolf; Haenschel, Corinna

    2015-09-01

    Behavioral evidence indicates that working memory (WM) in schizophrenia is already impaired at the encoding stage. However, the neurophysiological basis of this primary deficit remains poorly understood. Using event-related fMRI, we assessed differences in brain activation and functional connectivity during the encoding, maintenance and retrieval stages of a visual WM task with 3 levels of memory load in 17 adolescents with early-onset schizophrenia (EOS) and 17 matched controls. The amount of information patients could store in WM was reduced at all memory load levels. During encoding, activation in left ventrolateral prefrontal cortex (VLPFC) and extrastriate visual cortex, which in controls positively correlated with the amount of stored information, was reduced in patients. Additionally, patients showed disturbed functional connectivity between prefrontal and visual areas. During retrieval, right inferior VLPFC hyperactivation was correlated with hypoactivation of left VLPFC in patients during encoding. Visual WM encoding is disturbed by a failure to adequately engage a visual-prefrontal network critical for the transfer of perceptual information into WM. Prefrontal hyperactivation appears to be a secondary consequence of this primary deficit. Isolating the component processes of WM can lead to more specific neurophysiological markers for translational efforts seeking to improve the treatment of cognitive dysfunction in schizophrenia. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. Functional deterioration from the premorbid period to 2 years after the first episode of psychosis in early-onset psychosis.

    Science.gov (United States)

    Del Rey-Mejías, Ángel; Fraguas, David; Díaz-Caneja, Covadonga M; Pina-Camacho, Laura; Castro-Fornieles, Josefina; Baeza, Inmaculada; Espliego, Ana; Merchán-Naranjo, Jessica; González-Pinto, Ana; de la Serna, Elena; Payá, Beatriz; Graell, Montserrat; Arango, Celso; Parellada, Mara

    2015-12-01

    The aim of the study was to analyze changes in functional adjustment from childhood to 2 years after the first episode of psychosis (FEP) in patients with early-onset schizophrenia spectrum disorders (SSD) and affective psychoses (AFP) and a good or intermediate level of premorbid adjustment. We followed 106 adolescents (aged 12-17 years) with FEP for 2 years after recruitment. Premorbid adjustment in childhood was assessed in 98 patients with the childhood subscale of the Cannon-Spoor Premorbid Adjustment Scale (c-PAS). Global functioning was assessed 2 years after the FEP with the Children's Global Assessment Scale (c-GAS) or the Global Assessment of Functioning scale (GAF), as appropriate. Functional deterioration was defined as a downward shift in the level of functional adjustment from childhood to 2 years after the FEP. In patients with good or intermediate premorbid adjustment, functional deterioration was observed in 28.2 % (26.5 % of the AFP group, 29.4 % of the SSD group). Longer duration of untreated psychosis (Beta = 0.01; P = 0.01) and higher symptom severity at the FEP, as measured with the Clinical Global Impression Scale (Beta = 1.12; P = 0.02), significantly predicted the presence of functional deterioration, accounting for 21.4 % of the variance. Irrespective of diagnosis (SSD or AFP), almost one-third of adolescents with FEP and good or intermediate premorbid adjustment showed functional deterioration from the premorbid period to 2 years after the FEP.

  8. Intervention on early-onset conduct problems as indicated prevention for substance use: A seven-year follow up.

    Science.gov (United States)

    Romero, Estrella; Rodríguez, Concepción; Villar, Paula; Gómez-Fraguela, X Antón

    2017-06-28

    The aim of this study is to evaluate the long-term effects of a manualised program which intervenes on children with early-onset conduct problems, their families and teachers. The program evaluation involved 14 primary schools which were randomly assigned to the intervention (45 participating families) and control (30 families) conditions during 2007-2008. After a screening process which identified children with significant conduct problems both at home with their family and at school, the program was implemented in eight schools. Seven years later, 58 families (37 from the intervention group and 21 from the control group), with characteristics equivalent to those of the study's entire initial group, were contacted again. With measures administered to the children and their parents, comparisons through multivariate analyses of variance between intervention and control groups supported the program's efficacy in reducing both conduct problems and relations with antisocial peers. Furthermore, the program fostered social and communication skills. As regards drug use, the intervention group showed less favourable attitudes towards drugs, lower intention of drug use, lower frequency of tobacco use and lower intensity of alcohol use. These results support the usefulness of multicomponent programs for conduct problems as a way to prevent, in the long term, unfavourable developmental trajectories, where drug use is a key element.

  9. My Family-Study, Early-Onset Substance use Prevention Program: An Application of Intervention Mapping Approach

    Directory of Open Access Journals (Sweden)

    Mehdi Mirzaei-Alavijeh

    2017-03-01

    Full Text Available Background and Objectives: Based on different studies, substance use is one of the health problems in the Iranian society. The prevalence of substance use is on a growing trend; moreover, the age of the onset of substance use has declined to early adolescence and even lower. Regarding this, the present study aimed to develop a family-based early-onset substance use prevention program in children (My Family-Study by using intervention mapping approach. Materials and Methods: This study descirbes the research protocol during which the intervention mapping approach was used as a framework to develop My Family-Study. In this study, six steps of intervention mapping were completed. Interviews with experts and literature review fulfilled the need assessment. In the second step, the change objectivs were rewritten based on the intersection of the performance objectives and the determinants associated in the matrices. After designing the program and planning the implementation of the intervention, the evaluation plan of the program was accomplished. Results: The use of intervention mapping approach facilitated the develop-pment of a systematic as well as theory- and evidence-based program. Moreover, this approach was helful in the determination of outcomes, performance and change objectives, determinants, theoretical methods, practical application, intervention, dissemination, and evaluation program. Conclusions: The intervention mapping provided a systematic as well as theory- and evidence-based approach to develop a quality continuing health promotion program.

  10. Sedation, sucralfate, and antibiotic use are potential means for protection against early-onset ventilator-associated pneumonia.

    Science.gov (United States)

    Bornstain, C; Azoulay, E; De Lassence, A; Cohen, Y; Costa, M A; Mourvillier, B; Descorps-Declere, A; Garrouste-Orgeas, M; Thuong, M; Schlemmer, B; Timsit, J-F

    2004-05-15

    To examine risk factors for early-onset ventilator-associated pneumonia (EOP) in patients requiring mechanical ventilation (MV), we performed a prospective cohort study that included 747 patients. Pneumonia was defined as a positive result for a protected quantitative distal sample. EOP was defined as pneumonia that occurred from day 3 to day 7 of MV. Eighty patients (10.7%) experienced EOP. Independent predictors of EOP were male sex (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.18-3.63), actual Glasgow Coma Scale value of 6-13 (OR, 1.95; 95% CI, 1.2-3.18), high Logistic Organ Dysfunction score at day 2 (OR, 1.12 per point; 95% CI, 1.02-1.23), unplanned extubation (OR, 3.19; 95% CI, 1.28-7.92), and sucralfate use (OR, 1.81; 95% CI, 1.01-3.26). Protection occurred with use of aminoglycosides (OR, 0.36; 95% CI, 0.17-0.76), beta -lactams and/or beta -lactamase inhibitors (OR, 0.47; 95% CI, 0.28-0.83), or third-generation cephalosporins (OR, 0.33; 95% CI, 0.16-0.74). Sucralfate use and unplanned extubation are independent risk factors for EOP. Use of aminoglycosides, beta-lactams/ beta-lactamase inhibitors, or third-generation cephalosporins protects against EOP.

  11. Targeted gene panel sequencing in children with very early onset inflammatory bowel disease--evaluation and prospective analysis.

    Science.gov (United States)

    Kammermeier, Jochen; Drury, Suzanne; James, Chela T; Dziubak, Robert; Ocaka, Louise; Elawad, Mamoun; Beales, Philip; Lench, Nicholas; Uhlig, Holm H; Bacchelli, Chiara; Shah, Neil

    2014-11-01

    Multiple monogenetic conditions with partially overlapping phenotypes can present with inflammatory bowel disease (IBD)-like intestinal inflammation. With novel genotype-specific therapies emerging, establishing a molecular diagnosis is becoming increasingly important. We have introduced targeted next-generation sequencing (NGS) technology as a prospective screening tool in children with very early onset IBD (VEOIBD). We evaluated the coverage of 40 VEOIBD genes in two separate cohorts undergoing targeted gene panel sequencing (TGPS) (n=25) and whole exome sequencing (WES) (n=20). TGPS revealed causative mutations in four genes (IL10RA, EPCAM, TTC37 and SKIV2L) discovered unexpected phenotypes and directly influenced clinical decision making by supporting as well as avoiding haematopoietic stem cell transplantation. TGPS resulted in significantly higher median coverage when compared with WES, fewer coverage deficiencies and improved variant detection across established VEOIBD genes. Excluding or confirming known VEOIBD genotypes should be considered early in the disease course in all cases of therapy-refractory VEOIBD, as it can have a direct impact on patient management. To combine both described NGS technologies would compensate for the limitations of WES for disease-specific application while offering the opportunity for novel gene discovery in the research setting. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  12. Variation in lumbar punctures for early onset neonatal sepsis: a nationally representative serial cross-sectional analysis, 2003-2009

    Directory of Open Access Journals (Sweden)

    Patrick Stephen W

    2012-08-01

    Full Text Available Abstract Background Whether lumbar punctures (LPs should be performed routinely for term newborns suspected of having early onset neonatal sepsis (EONS is subject to debate. It is unclear whether variations in performance of LPs for EONS may be associated with patient, hospital, insurance or regional factors. Our objective was to identify characteristics associated with the practice of performing LPs for suspected EONS in a nationally representative sample. Methods Utilizing data from the 2003, 2006 and 2009 Kids’ Inpatient Database (KID compiled by the Agency for Healthcare Research and Quality, we examined the frequency and characteristics of term, normal-birth weight newborns receiving an LP for EONS. Survey-weighting was applied for national estimates and used in chi squared and multivariable regression analysis. Results In 2009, there were 13,694 discharges for term newborns that underwent LPs for apparent EONS. Newborns having LPs performed were more likely to be covered by Medicaid vs. private insurance (51.9 vs. 45.1 percent; p Conclusions We found pronounced variation in LPs performed for EONS, even when adjusting for clinical conditions that would prompt LPs. These findings indicate practice variations in newborn care that merit further examination and explanation.

  13. Early-Onset Acute Recurrent and Chronic Pancreatitis Is Associated with PRSS1 or CTRC Gene Mutations.

    Science.gov (United States)

    Giefer, Matthew J; Lowe, Mark E; Werlin, Steven L; Zimmerman, Bridget; Wilschanski, Michael; Troendle, David; Schwarzenberg, Sarah Jane; Pohl, John F; Palermo, Joseph; Ooi, Chee Y; Morinville, Veronique D; Lin, Tom K; Husain, Sohail Z; Himes, Ryan; Heyman, Melvin B; Gonska, Tanja; Gariepy, Cheryl E; Freedman, Steven D; Fishman, Douglas S; Bellin, Melena D; Barth, Bradley; Abu-El-Haija, Maisam; Uc, Aliye

    2017-07-01

    To assess whether the age of onset was associated with unique features or disease course in pediatric acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP). Demographic and clinical information on children with ARP or CP was collected at INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE) centers. The Cochran-Armitage trend test and Jonckheere-Terpstra test were used to examine for differences between pediatric age groups (pancreatitis, 111 (32%) were 6-11 years of age, and 102 (30%) were ≥12 years of age. Early-onset disease was associated with mutations in cationic trypsinogen (PRSS1) (P pancreatitis (P = .02), family history of CP (P chronic renal failure (P = .02). Later-onset disease was more commonly present with hypertriglyceridemia (P = .04), ulcerative colitis (P = .02), autoimmune diseases (P pancreatitis is associated strongly with PRSS1 or CTRC mutations and family history of pancreatitis. Children with later-onset disease are more likely to have nongenetic risk factors. Future studies are needed to investigate whether the disease course, response to therapy, or clinical outcomes differ relative to the timing of disease onset. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Intrapartum Antibiotic Chemoprophylaxis Policies for the Prevention of Group B Streptococcal Disease Worldwide: Systematic Review.

    Science.gov (United States)

    Le Doare, Kirsty; O'Driscoll, Megan; Turner, Kim; Seedat, Farah; Russell, Neal J; Seale, Anna C; Heath, Paul T; Lawn, Joy E; Baker, Carol J; Bartlett, Linda; Cutland, Clare; Gravett, Michael G; Ip, Margaret; Madhi, Shabir A; Rubens, Craig E; Saha, Samir K; Schrag, Stephanie; Sobanjo-Ter Meulen, Ajoke; Vekemans, Johan; Kampmann, Beate

    2017-11-06

    Intrapartum antibiotic chemoprophylaxis (IAP) prevents most early-onset group B streptococcal (GBS) disease. However, there is no description of how IAP is used around the world. This article is the sixth in a series estimating the burden of GBS disease. Here we aimed to review GBS screening policies and IAP implementation worldwide. We identified data through (1) systematic literature reviews (PubMed/Medline, Embase, Literature in the Health Sciences in Latin America and the Caribbean [LILACS], World Health Organization library database [WHOLIS], and Scopus) and unpublished data from professional societies and (2) an online survey and searches of policies from medical societies and professionals. We included data on whether an IAP policy was in use, and if so whether it was based on microbiological or clinical risk factors and how these were applied, as well as the estimated coverage (percentage of women receiving IAP where indicated). We received policy information from 95 of 195 (49%) countries. Of these, 60 of 95 (63%) had an IAP policy; 35 of 60 (58%) used microbiological screening, 25 of 60 (42%) used clinical risk factors. Two of 15 (13%) low-income, 4 of 16 (25%) lower-middle-income, 14 of 20 (70%) upper-middle-income, and 40 of 44 (91%) high-income countries had any IAP policy. The remaining 35 of 95 (37%) had no national policy (25/33 from low-income and lower-middle-income countries). Coverage varied considerably; for microbiological screening, median coverage was 80% (range, 20%-95%); for clinical risk factor-based screening, coverage was 29% (range, 10%-50%). Although there were differences in the microbiological screening methods employed, the individual clinical risk factors used were similar. There is considerable heterogeneity in IAP screening policies and coverage worldwide. Alternative global strategies, such as maternal vaccination, are needed to enhance the scope of global prevention of GBS disease. © The Author 2017. Published by Oxford

  15. 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.

  16. Defects in Nicotinamide-adenine Dinucleotide Phosphate Oxidase Genes NOX1 and DUOX2 in Very Early Onset Inflammatory Bowel DiseaseSummary

    Directory of Open Access Journals (Sweden)

    Patti Hayes

    2015-09-01

    Full Text Available Background & Aims: Defects in intestinal innate defense systems predispose patients to inflammatory bowel disease (IBD. Reactive oxygen species (ROS generated by nicotinamide-adenine dinucleotide phosphate (NADPH oxidases in the mucosal barrier maintain gut homeostasis and defend against pathogenic attack. We hypothesized that molecular genetic defects in intestinal NADPH oxidases might be present in children with IBD. Methods: After targeted exome sequencing of epithelial NADPH oxidases NOX1 and DUOX2 on 59 children with very early onset inflammatory bowel disease (VEOIBD, the identified mutations were validated using Sanger Sequencing. A structural analysis of NOX1 and DUOX2 variants was performed by homology in silico modeling. The functional characterization included ROS generation in model cell lines and in in vivo transduced murine crypts, protein expression, intracellular localization, and cell-based infection studies with the enteric pathogens Campylobacter jejuni and enteropathogenic Escherichia coli. Results: We identified missense mutations in NOX1 (c.988G>A, p.Pro330Ser; c.967G>A, p.Asp360Asn and DUOX2 (c.4474G>A, p.Arg1211Cys; c.3631C>T, p.Arg1492Cys in 5 of 209 VEOIBD patients. The NOX1 p.Asp360Asn variant was replicated in a male Ashkenazi Jewish ulcerative colitis cohort. Patients with both NOX1 and DUOX2 variants showed abnormal Paneth cell metaplasia. All NOX1 and DUOX2 variants showed reduced ROS production compared with wild-type enzymes. Despite appropriate cellular localization and comparable pathogen-stimulated translocation of altered oxidases, cells harboring NOX1 or DUOX2 variants had defective host resistance to infection with C. jejuni. Conclusions: This study identifies the first inactivating missense variants in NOX1 and DUOX2 associated with VEOIBD. Defective ROS production from intestinal epithelial cells constitutes a risk factor for developing VEOIBD. Keywords: Inflammatory Bowel Disease, NADPH Oxidase

  17. 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.

  18. 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

  19. 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.

  20. Genome-wide identification of blood DNA methylation patterns associated with early-onset hepatocellular carcinoma development in hepatitis B carriers.

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    Kao, Wei-Yi; Yang, Shu-Han; Liu, Wen-Jie; Yeh, Meng-Yin; Lin, Chih-Lin; Liu, Chun-Jen; Huang, Chi-Jung; Lin, Shi-Ming; Lee, Shou-Dong; Chen, Pei-Jer; Yu, Ming-Whei

    2017-02-01

    The etiology of early-onset hepatocellular carcinoma (HCC) among hepatitis B virus (HBV) carriers remains unclear. DNA methylation levels in peripheral leukocytes have been associated with different environmental exposures and immune or inflammatory response. We aimed to identify methylation signatures of peripheral leukocytes that could track hepatitis B progression to HCC, especially for early-onset HCC. We first performed an epigenome-wide association analysis on 48 matched case-control pairs in a nested case-control study within a 22-yr follow-up cohort of HBV carriers. Through this analysis we found that progression to early-onset HCC involved methylation variable positions across the genome, in which a substantial proportion displayed significant variation due to HBV viral load, chronic hepatitis status, and/or leukocyte subtype composition, and these associations were significantly enriched among genes in immune pathways. Methylation at probes cg00300879, cg06872964, and cg07080864, that are located within the proximal promoter of CNKSR1, IFI44L, and PENK, respectively, was validated by bisulfite pyrosequencing and findings were replicated in a case-sibling study of early-onset HCC (134 cases vs. 174 sibling controls). Furthermore, a high methylation score, constructed using the three probes, was predictive for the risk of early-onset HCC in two datasets (adjusted-odds ratios = 0.21-0.32, P ≤ 0.0206). This association was also observed for late-onset HCC (adjusted-odds ratio = 0.42-0.47, P ≤ 0.0194) in a nested case-control study (120 cases vs. 178 controls). In prospective analysis, change in the score was detected 5-9 yr before HCC onset. Blood-based methylation profiling provides new insights into the complexity of virus-host interaction underlying HBV-related HCC, holding promise for the disease risk management. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. Streptococcal toxic-shock syndrome due to Streptococcus dysgalactiae subspecies equisimilis in breast cancer-related lymphedema: a case report.

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    Sumazaki, Makoto; Saito, Fumi; Ogata, Hideaki; Yoshida, Miho; Kubota, Yorichika; Magoshi, Syunsuke; Kaneko, Hironori

    2017-07-14

    Breast cancer-related lymphedema often causes cellulitis and is one of the most common complications after breast cancer surgery. Streptococci are the major pathogens underlying such cellulitis. Among the streptococci, the importance of the Lancefield groups C and G is underappreciated; most cases involve Streptococcus dysgalactiae subspecies equisimilis. Despite having a relatively weak toxicity compared with group A streptococci, Streptococcus dysgalactiae subspecies equisimilis is associated with a mortality rate that is as high as that of group A streptococci in cases of invasive infection because Streptococcus dysgalactiae subspecies equisimilis mainly affects elderly individuals who already have various comorbidities. An 83-year-old Japanese woman with breast cancer-related lymphedema in her left upper limb was referred to our hospital with high fever and acute pain with erythema in her left arm. She showed septic shock with disseminated intravascular coagulation. Blood culture showed positive results for Streptococcus dysgalactiae subspecies equisimilis, confirming a diagnosis of streptococcal toxic-shock syndrome. She survived after successful intensive care. To the best of our knowledge, this case represents the first report of Streptococcus dysgalactiae subspecies equisimilis-induced streptococcal toxic-shock syndrome in a patient with breast cancer-related lymphedema. Breast cancer-related lymphedema is a common problem, and we must pay attention to invasive streptococcal soft tissue infections, particularly in elderly patients with chronic disease.

  2. Routine culture-based screening versus risk-based management for the prevention of early-onset group B streptococcus disease in the neonate: a systematic review.

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    Kurz, Ella; Davis, Deborah

    2015-04-17

    Early-onset group B streptococcus disease, recognized as the most common cause of early onset neonatal sepsis in developed countries, is transmitted vertically from the group B streptococcus carrier mother to the neonate in the peripartum. Accordingly, early-onset group B streptococcus disease is prevented by halting the transmission of the microorganism from the mother to the infant. Two main methods, routine culture-based screening and risk-based management, may be used in the identification of mothers requiring intrapartum antibiotic prophylaxis in labor. While there are advantages and disadvantages to each, there is limited high level evidence available as to which method is superior. To identify the effectiveness of risk-based management versus routine culture-based screening in the prevention of early-onset group B streptococcus disease in the neonate. This review considered studies which treated pregnant women with intrapartum antibiotic prophylaxis following risk- and culture-based protocols for the prevention of early-onset group B streptococcus disease in the neonate. Types of intervention: This review considered studies that evaluated risk-based management against routine culture-based screening for the prevention of early-onset group B streptococcus disease in the neonate. Types of studies: This review looked for highest evidence available which in this case consisted of one quasi experimental study and eight comparative cohort studies with historical or concurrent control groups. Types of outcomes: Incidence of early-onset group B streptococcus disease in neonates as measured by positive group B streptococcus culture from an otherwise sterile site. Secondary outcomes include neonatal death due to group B streptococcus sepsis and percentage of women who received intrapartum antibiotic prophylaxis. A multi-step search strategy was used to find studies which were limited to the English language and published between January 2000 and June 2013. The quality

  3. A genetic screen of the mutations in the Korean patients with early-onset Alzheimer’s disease

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    An SS

    2016-12-01

    Full Text Available Seong Soo An,1,* Sun Ah Park,2,* Eva Bagyinszky,1 Sun Oh Bae,1 Yoon-Jeong Kim,2 Ji Young Im,2 Kyung Won Park,3 Kee Hyung Park,4 Eun-Joo Kim,5 Jee Hyang Jeong,6 Jong Hun Kim,7 Hyun Jeong Han,8 Seong Hye Choi,9 SangYun Kim10 1Department of Bionano Technology, Gachon University, Seongnam-si, 2Department of Neurology, Soonchunhyang University Bucheon Hospital, Bucheon, 3Department of Neurology, Dong-A University College of Medicine and Institute of Convergence Bio-Health, Busan, 4Department of Neurology, Gachon University Gil Medical Center, Incheon, 5Department of Neurology, Pusan National University Hospital, Busan, 6Department of Neurology, Ewha Womans University Mokdong Hospital, Seoul, 7Department of Neurology, Ilsan Hospital, National Health Insurance Corporation, 8Department of Neurology, Myongii Hospital, Goyang, 9Department of Neurology, Inha University School of Medicine, Incheon, 10Department of Neurology, Seoul National University College of Medicine & Neurocognitive Behavior Center, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea *These authors contributed equally to this work Abstract: Early-onset Alzheimer’s disease (EOAD has distinct clinical characteristics in comparison to late-onset Alzheimer’s disease (LOAD. The genetic contribution is suggested to be more potent in EOAD. However, the frequency of causative mutations in EOAD could be variable depending on studies. Moreover, no mutation screening study has been performed yet employing large population in Korea. Previously, we reported that the rate of family history of dementia in EOAD patients was 18.7% in a nationwide hospital-based cohort study, the Clinical Research Center for Dementia of South Korea (CREDOS study. This rate is much lower than in other countries and is even comparable to the frequency of LOAD patients in our country. To understand the genetic characteristics of EOAD in Korea, we screened the common Alzheimer’s disease (AD

  4. MicroRNAs and Target Genes As Biomarkers for the Diagnosis of Early Onset of Parkinson Disease

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    Ahmad R. Arshad

    2017-10-01

    Full Text Available Among the neurodegenerative disorders, Parkinson's disease (PD ranks as the second most common disorder with a higher prevalence in individuals aged over 60 years old. Younger individuals may also be affected with PD which is known as early onset PD (EOPD. Despite similarities between the characteristics of EOPD and late onset PD (LODP, EOPD patients experience much longer disease manifestations and poorer quality of life. Although some individuals are more prone to have EOPD due to certain genetic alterations, the molecular mechanisms that differentiate between EOPD and LOPD remains unclear. Recent findings in PD patients revealed that there were differences in the genetic profiles of PD patients compared to healthy controls, as well as between EOPD and LOPD patients. There were variants identified that correlated with the decline of cognitive and motor symptoms as well as non-motor symptoms in PD. There were also specific microRNAs that correlated with PD progression, and since microRNAs have been shown to be involved in the maintenance of neuronal development, mitochondrial dysfunction and oxidative stress, there is a strong possibility that these microRNAs can be potentially used to differentiate between subsets of PD patients. PD is mainly diagnosed at the late stage, when almost majority of the dopaminergic neurons are lost. Therefore, identification of molecular biomarkers for early detection of PD is important. Given that miRNAs are crucial in controlling the gene expression, these regulatory microRNAs and their target genes could be used as biomarkers for early diagnosis of PD. In this article, we discussed the genes involved and their regulatory miRNAs, regarding their roles in PD progression, based on the findings of significantly altered microRNAs in EOPD studies. We also discussed the potential of these miRNAs as molecular biomarkers for early diagnosis.

  5. Early-onset sleep defects in Drosophila models of Huntington's disease reflect alterations of PKA/CREB signaling

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    Gonzales, Erin D.; Tanenhaus, Anne K.; Zhang, Jiabin; Chaffee, Ryan P.; Yin, Jerry C.P.

    2016-01-01

    Huntington's disease (HD) is a progressive neurological disorder whose non-motor symptoms include sleep disturbances. Whether sleep and activity abnormalities are primary molecular disruptions of mutant Huntingtin (mutHtt) expression or result from neurodegeneration is unclear. Here, we report Drosophila models of HD exhibit sleep and activity disruptions very early in adulthood, as soon as sleep patterns have developed. Pan-neuronal expression of full-length or N-terminally truncated mutHtt recapitulates sleep phenotypes of HD patients: impaired sleep initiation, fragmented and diminished sleep, and nighttime hyperactivity. Sleep deprivation of HD model flies results in exacerbated sleep deficits, indicating that homeostatic regulation of sleep is impaired. Elevated PKA/CREB activity in healthy flies produces patterns of sleep and activity similar to those in our HD models. We were curious whether aberrations in PKA/CREB signaling were responsible for our early-onset sleep/activity phenotypes. Decreasing signaling through the cAMP/PKA pathway suppresses mutHtt-induced developmental lethality. Genetically reducing PKA abolishes sleep/activity deficits in HD model flies, restores the homeostatic response and extends median lifespan. In vivo reporters, however, show dCREB2 activity is unchanged, or decreased when sleep/activity patterns are abnormal, suggesting dissociation of PKA and dCREB2 occurs early in pathogenesis. Collectively, our data suggest that sleep defects may reflect a primary pathological process in HD, and that measurements of sleep and cAMP/PKA could be prodromal indicators of disease, and serve as therapeutic targets for intervention. PMID:26604145

  6. Methylation of Breast Cancer Predisposition Genes in Early-Onset Breast Cancer: Australian Breast Cancer Family Registry.

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    Cameron M Scott

    Full Text Available DNA methylation can mimic the effects of both germline and somatic mutations for cancer predisposition genes such as BRCA1 and p16INK4a. Constitutional DNA methylation of the BRCA1 promoter has been well described and is associated with an increased risk of early-onset breast cancers that have BRCA1-mutation associated histological features. The role of methylation in the context of other breast cancer predisposition genes has been less well studied and often with conflicting or ambiguous outcomes. We examined the role of methylation in known breast cancer susceptibility genes in breast cancer predisposition and tumor development. We applied the Infinium HumanMethylation450 Beadchip (HM450K array to blood and tumor-derived DNA from 43 women diagnosed with breast cancer before the age of 40 years and measured the methylation profiles across promoter regions of BRCA1, BRCA2, ATM, PALB2, CDH1, TP53, FANCM, CHEK2, MLH1, MSH2, MSH6 and PMS2. Prior genetic testing had demonstrated that these women did not carry a germline mutation in BRCA1, ATM, CHEK2, PALB2, TP53, BRCA2, CDH1 or FANCM. In addition to the BRCA1 promoter region, this work identified regions with variable methylation at multiple breast cancer susceptibility genes including PALB2 and MLH1. Methylation at the region of MLH1 in these breast cancers was not associated with microsatellite instability. This work informs future studies of the role of methylation in breast cancer susceptibility gene silencing.

  7. Novel Variants in ZNF34 and Other Brain-Expressed Transcription Factors are Shared Among Early-Onset MDD Relatives

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    Subaran, Ryan L.; Odgerel, Zagaa; Swaminathan, Rajeswari; Glatt, Charles E.; Weissman, Myrna M.

    2018-01-01

    There are no known genetic variants with large effects on susceptibility to major depressive disorder (MDD). Although one proposed study approach is to increase sensitivity by increasing sample sizes, another is to focus on families with multiple affected individuals to identify genes with rare or novel variants with strong effects. Choosing the family-based approach, we performed whole-exome analysis on affected individuals (n = 12) across five MDD families, each with at least five affected individuals, early onset, and prepubertal diagnoses. We identified 67 genes where novel deleterious variants were shared among affected relatives. Gene ontology analysis shows that of these 67 genes, 18 encode transcriptional regulators, eight of which are expressed in the human brain, including four KRAB-A box-containing Zn2+ finger repressors. One of these, ZNF34, has been reported as being associated with bipolar disorder and as differentially expressed in bipolar disorder patients compared to healthy controls. We found a novel variant—encoding a non-conservative P17R substitution in the conserved repressor domain of ZNF34 protein—segregating completely with MDD in all available individuals in the family in which it was discovered. Further analysis showed a common ZNF34 coding indel segregating with MDD in a separate family, possibly indicating the presence of an unobserved, linked, rare variant in that particular family. Our results indicate that genes encoding transcription factors expressed in the brain might be an important group of MDD candidate genes and that rare variants in ZNF34 might contribute to susceptibility to MDD and perhaps other affective disorders. PMID:26823146

  8. Early onset hyperuricemia is a prognostic marker for kidney graft failure: Propensity score matching analysis in a Korean multicenter cohort.

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    Miyeun Han

    Full Text Available It remains inconclusive whether hyperuricemia is a true risk factor for kidney graft failure. In the current study, we investigated the association of hyperuricemia and graft outcome. We performed a multi-center cohort study that included 2620 kidney transplant recipients. The patients were classified as either normouricemic or hyperuricemic at 3 months after transplantation. Hyperuricemia was defined as a serum uric acid level ≥ 7.0 mg/dL in males or ≥ 6.0 mg/dL in females or based on the use of urate-lowering medications. The two groups were compared before and after propensity score matching. A total of 657 (25.1% patients were classified as hyperuricemic. The proportion of hyperuricemic patients increased over time, reaching 44.2% of the total cohort at 5 years after transplantation. Estimated glomerular filtration rate and donor type were independently associated with hyperuricemia. Hyperuricemia was associated with graft loss according to multiple Cox regression analysis before propensity score matching (hazard ratio [HR] = 1.56, 95% confidence interval [CI] = 1.14-2.13, P = 0.005 as well as after matching (HR = 1.65, 95% CI = 1.13-2.42, p = 0.010. Cox regression models using time-varying hyperuricemia or marginal structural models adjusted with time-varying eGFR also demonstrated significant hazards of hyperuricemia for graft loss. Cardiovascular events and recipient survival were not associated with hyperuricemia. Overall, hyperuricemia, especially early onset after transplantation, showed an increased risk for graft failure. Further studies are warranted to determine whether lowering serum uric acid levels would be beneficial to graft survival.

  9. Direct diabetes-related costs in young patients with early-onset, long-lasting type 1 diabetes.

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    Christina Bächle

    Full Text Available OBJECTIVE: To estimate diabetes-related direct health care costs in pediatric patients with early-onset type 1 diabetes of long duration in Germany. RESEARCH DESIGN AND METHODS: Data of a population-based cohort of 1,473 subjects with type 1 diabetes onset at 0-4 years of age within the years 1993-1999 were included (mean age 13.9 (SD 2.2 years, mean diabetes duration 10.9 (SD 1.9 years, as of 31.12.2007. Diabetes-related health care services utilized in 2007 were derived from a nationwide prospective documentation system (DPV. Health care utilization was valued in monetary terms based on inpatient and outpatient medical fees and retail prices (perspective of statutory health insurance. Multiple regression models were applied to assess associations between direct diabetes-related health care costs per patient-year and demographic and clinical predictors. RESULTS: Mean direct diabetes-related health care costs per patient-year were €3,745 (inter-quartile range: 1,943-4,881. Costs for glucose self-monitoring were the main cost category (28.5%, followed by costs for continuous subcutaneous insulin infusion (25.0%, diabetes-related hospitalizations (22.1% and insulin (18.4%. Female gender, pubertal age and poor glycemic control were associated with higher and migration background with lower total costs. CONCLUSIONS: Main cost categories in patients with on average 11 years of diabetes duration were costs for glucose self-monitoring, insulin pump therapy, hospitalization and insulin. Optimization of glycemic control in particular in pubertal age through intensified care with improved diabetes education and tailored insulin regimen, can contribute to the reduction of direct diabetes-related costs in this patient group.

  10. Screening of dementia genes by whole-exome sequencing in early-onset Alzheimer disease: input and lessons.

    Science.gov (United States)

    Nicolas, Gaël; Wallon, David; Charbonnier, Camille; Quenez, Olivier; Rousseau, Stéphane; Richard, Anne-Claire; Rovelet-Lecrux, Anne; Coutant, Sophie; Le Guennec, Kilan; Bacq, Delphine; Garnier, Jean-Guillaume; Olaso, Robert; Boland, Anne; Meyer, Vincent; Deleuze, Jean-François; Munter, Hans Markus; Bourque, Guillaume; Auld, Daniel; Montpetit, Alexandre; Lathrop, Mark; Guyant-Maréchal, Lucie; Martinaud, Olivier; Pariente, Jérémie; Rollin-Sillaire, Adeline; Pasquier, Florence; Le Ber, Isabelle; Sarazin, Marie; Croisile, Bernard; Boutoleau-Bretonnière, Claire; Thomas-Antérion, Catherine; Paquet, Claire; Sauvée, Mathilde; Moreaud, Olivier; Gabelle, Audrey; Sellal, François; Ceccaldi, Mathieu; Chamard, Ludivine; Blanc, Frédéric; Frebourg, Thierry; Campion, Dominique; Hannequin, Didier

    2016-05-01

    Causative variants in APP, PSEN1 or PSEN2 account for a majority of cases of autosomal dominant early-onset Alzheimer disease (ADEOAD, onset before 65 years). Variant detection rates in other EOAD patients, that is, with family history of late-onset AD (LOAD) (and no incidence of EOAD) and sporadic cases might be much lower. We analyzed the genomes from 264 patients using whole-exome sequencing (WES) with high depth of coverage: 90 EOAD patients with family history of LOAD and no incidence of EOAD in the family and 174 patients with sporadic AD starting between 51 and 65 years. We found three PSEN1 and one PSEN2 causative, probably or possibly causative variants in four patients (1.5%). Given the absence of PSEN1, PSEN2 and APP causative variants, we investigated whether these 260 patients might be burdened with protein-modifying variants in 20 genes that were previously shown to cause other types of dementia when mutated. For this analysis, we included an additional set of 160 patients who were previously shown to be free of causative variants in PSEN1, PSEN2 and APP: 107 ADEOAD patients and 53 sporadic EOAD patients with an age of onset before 51 years. In these 420 patients, we detected no variant that might modify the function of the 20 dementia-causing genes. We conclude that EOAD patients with family history of LOAD and no incidence of EOAD in the family or patients with sporadic AD starting between 51 and 65 years have a low variant-detection rate in AD genes.

  11. Clonal heterogeneity of thymic B cells from early-onset myasthenia gravis patients with antibodies against the acetylcholine receptor.

    Science.gov (United States)

    Vrolix, Kathleen; Fraussen, Judith; Losen, Mario; Stevens, Jo; Lazaridis, Konstantinos; Molenaar, Peter C; Somers, Veerle; Bracho, Maria Alma; Le Panse, Rozen; Stinissen, Piet; Berrih-Aknin, Sonia; Maessen, Jos G; Van Garsse, Leen; Buurman, Wim A; Tzartos, Socrates J; De Baets, Marc H; Martinez-Martinez, Pilar

    2014-08-01

    Myasthenia gravis (MG) with antibodies against the acetylcholine receptor (AChR-MG) is considered as a prototypic autoimmune disease. The thymus is important in the pathophysiology of the disease since thymus hyperplasia is a characteristic of early-onset AChR-MG and patients often improve after thymectomy. We hypothesized that thymic B cell and antibody repertoires of AChR-MG patients differ intrinsically from those of control individuals. Using immortalization with Epstein-Barr Virus and Toll-like receptor 9 activation, we isolated and characterized monoclonal B cell lines from 5 MG patients and 8 controls. Only 2 of 570 immortalized B cell clones from MG patients produced antibodies against the AChR (both clones were from the same patient), suggesting that AChR-specific B cells are not enriched in the thymus. Surprisingly, many B cell lines from both AChR-MG and control thymus samples displayed reactivity against striated muscle proteins. Striational antibodies were produced by 15% of B cell clones from AChR-MG versus 6% in control thymus. The IgVH gene sequence analysis showed remarkable similarities, concerning VH family gene distribution, mutation frequency and CDR3 composition, between B cells of AChR-MG patients and controls. MG patients showed clear evidence of clonal B cell expansion in contrast to controls. In this latter aspect, MG resembles multiple sclerosis and clinically isolated syndrome, but differs from systemic lupus erythematosus. Our results support an antigen driven immune response in the MG thymus, but the paucity of AChR-specific B cells, in combination with the observed polyclonal expansions suggest a more diverse immune response than expected. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Rare variants in calcium homeostasis modulator 1 (CALHM1 found in early onset Alzheimer's disease patients alter calcium homeostasis.

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    Fanny Rubio-Moscardo

    Full Text Available Calcium signaling in the brain is fundamental to the learning and memory process and there is evidence to suggest that its dysfunction is involved in the pathological pathways underlying Alzheimer's disease (AD. Recently, the calcium hypothesis of AD has received support with the identification of the non-selective Ca(2+-permeable channel CALHM1. A genetic polymorphism (p. P86L in CALHM1 reduces plasma membrane Ca(2+ permeability and is associated with an earlier age-at-onset of AD. To investigate the role of CALHM1 variants in early-onset AD (EOAD, we sequenced all CALHM1 coding regions in three independent series comprising 284 EOAD patients and 326 controls. Two missense mutations in patients (p.G330D and p.R154H and one (p.A213T in a control individual were identified. Calcium imaging analyses revealed that while the mutation found in a control (p.A213T behaved as wild-type CALHM1 (CALHM1-WT, a complete abolishment of the Ca(2+ influx was associated with the mutations found in EOAD patients (p.G330D and p.R154H. Notably, the previously reported p. P86L mutation was associated with an intermediate Ca(2+ influx between the CALHM1-WT and the p.G330D and p.R154H mutations. Since neither expression of wild-type nor mutant CALHM1 affected amyloid ß-peptide (Aß production or Aß-mediated cellular toxicity, we conclude that rare genetic variants in CALHM1 lead to Ca(2+ dysregulation and may contribute to the risk of EOAD through a mechanism independent from the classical Aß cascade.

  13. Biallelic Mutations in TBCD, Encoding the Tubulin Folding Cofactor D, Perturb Microtubule Dynamics and Cause Early-Onset Encephalopathy.

    Science.gov (United States)

    Flex, Elisabetta; Niceta, Marcello; Cecchetti, Serena; Thiffault, Isabelle; Au, Margaret G; Capuano, Alessandro; Piermarini, Emanuela; Ivanova, Anna A; Francis, Joshua W; Chillemi, Giovanni; Chandramouli, Balasubramanian; Carpentieri, Giovanna; Haaxma, Charlotte A; Ciolfi, Andrea; Pizzi, Simone; Douglas, Ganka V; Levine, Kara; Sferra, Antonella; Dentici, Maria Lisa; Pfundt, Rolph R; Le Pichon, Jean-Baptiste; Farrow, Emily; Baas, Frank; Piemonte, Fiorella; Dallapiccola, Bruno; Graham, John M; Saunders, Carol J; Bertini, Enrico; Kahn, Richard A; Koolen, David A; Tartaglia, Marco

    2016-10-06

    Microtubules are dynamic cytoskeletal elements coordinating and supporting a variety of neuronal processes, including cell division, migration, polarity, intracellular trafficking, and signal transduction. Mutations in genes encoding tubulins and microtubule-associated proteins are known to cause neurodevelopmental and neurodegenerative disorders. Growing evidence suggests that altered microtubule dynamics may also underlie or contribute to neurodevelopmental disorders and neurodegeneration. We report that biallelic mutations in TBCD, encoding one of the five co-chaperones required for assembly and disassembly of the αβ-tubulin heterodimer, the structural unit of microtubules, cause a disease with neurodevelopmental and neurodegenerative features characterized by early-onset cortical atrophy, secondary hypomyelination, microcephaly, thin corpus callosum, developmental delay, intellectual disability, seizures, optic atrophy, and spastic quadriplegia. Molecular dynamics simulations predicted long-range and/or local structural perturbations associated with the disease-causing mutations. Biochemical analyses documented variably reduced levels of TBCD, indicating relative instability of mutant proteins, and defective β-tubulin binding in a subset of the tested mutants. Reduced or defective TBCD function resulted in decreased soluble α/β-tubulin levels and accelerated microtubule polymerization in fibroblasts from affected subjects, demonstrating an overall shift toward a more rapidly growing and stable microtubule population. These cells displayed an aberrant mitotic spindle with disorganized, tangle-shaped microtubules and reduced aster formation, which however did not alter appreciably the rate of cell proliferation. Our findings establish that defective TBCD function underlies a recognizable encephalopathy and drives accelerated microtubule polymerization and enhanced microtubule stability, underscoring an additional cause of altered microtubule dynamics with

  14. 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.

  15. Physical and Sexual Abuse and Early-Onset Bipolar Disorder in Youths Receiving Outpatient Services: Frequent, but Not Specific

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    Youngstrom, Eric A.; Martinez, Maria; KogosYoungstrom, Jennifer; Scovil, Kelly; Ross, Jody; Feeny, Norah C.; Findling, Robert L.

    2014-01-01

    The objective of this study was to determine if physical and sexual abuse showed relationships to early-onset bipolar spectrum disorders (BPSD) consistent with findings from adult retrospective data. Participants (N=829, M= 10.9 years old ±3.4 SD, 60 % male, 69 % African American, and 18 % with BPSD), primarily from a low socio-economic status, presented to an urban community mental health center and a university research center. Physical abuse was reported in 21 %, sexual abuse in 20 %, and both physical and sexual abuse in 11 % of youths with BPSD. For youths without BPSD, physical abuse was reported in 16 %, sexual abuse in 15 %, and both physical and sexual abuse in 5 % of youths. Among youth with BPSD, physical abuse was significantly associated with a worse global family environment, more severe depressive and manic symptoms, a greater number of sub-threshold manic/hypomanic symptoms, a greater likelihood of suicidality, a greater likelihood of being diagnosed with PTSD, and more self-reports of alcohol or drug use. Among youth with BPSD, sexual abuse was significantly associated with a worse global family environment, more severe manic symptoms, a greater number of sub-threshold manic/hypomanic symptoms, greater mood swings, more frequent episodes, more reports of past hospitalizations, and a greater number of current and past comorbid Axis I diagnoses. These findings suggest that if physical and/or sexual abuse is reported, clinicians should note that abuse appears to be related to increased severity of symptoms, substance use, greater co-morbidity, suicidality, and a worse family environment. PMID:25118660

  16. Early-onset inguinal hernia as risk factor for schizophrenia or related psychosis: a nationwide register-based cohort study.

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    Melkersson, Kristina; Wernroth, Mona-Lisa

    2017-10-01

    In an earlier interview study, we found that more men with familial schizophrenia had undergone inguinal hernia operation, than men with sporadic schizophrenia. However, there are no other studies published specifically on inguinal hernia and schizophrenia. Therefore, the aim of this study was to carry out a Swedish register-based cohort study on the association between inguinal hernia and schizophrenia or related psychosis. Data from the Total Population- and Medical Birth-Registers were used to create a cohort of all individuals born in Sweden 1987-1999 (n=1 406 168). The cohort individuals were linked with the In- and Out-patient Registers and followed from birth to 2015 to identify onset of schizophrenia, schizoaffective disorder and inguinal hernia. Cox proportional hazards regression models were used to assess the association between inguinal hernia before age 13 and risk of developing schizophrenia or schizoaffective disorder during a follow-up from age 13. Inguinal hernia before age 13 was identified in 21 095 individuals, and during the follow-up in total 1314 individuals developed schizophrenia or schizoaffective disorder. The risk of schizophrenia or schizoaffective disorder was higher among individuals with inguinal hernia before age 13, than among individuals without such a diagnosis, especially among the men [adjusted hazard ratio (95% confidence interval); all: 1.44 (1.01-2.06), p=0.0452, men: 1.46 (1.01-2.12), p=0.0460, women: 0.56 (0.14-2.27), p=0.4173]. This study shows that early-onset inguinal hernia is associated with increased risk of developing schizophrenia or schizoaffective disorder, especially in men. Such an association may point to a common biological basis for the development of inguinal hernia and schizophrenia or related psychosis.

  17. Effect of administration of Streptococcus salivarius K12 on the occurrence of streptococcal pharyngo-tonsillitis, scarlet fever and acute otitis media in 3 years old children.

    Science.gov (United States)

    Di Pierro, F; Colombo, M; Giuliani, M G; Danza, M L; Basile, I; Bollani, T; Conti, A M; Zanvit, A; Rottoli, A S

    2016-11-01

    Streptococcus salivarius K12 (BLIS K12) is a probiotic strain strongly antagonistic to the growth of Streptococcus pyogenes, the most important bacterial cause of pharyngeal infections in humans. Shown to colonize the oral cavity and to be safe for human use, BLIS K12 has previously been reported to reduce pharyngo-tonsillitis episodes in children or adults known to have experienced recurrent streptococcal infection. The present study was focussed upon evaluating the role of BLIS K12 in the control of streptococcal disease and acute otitis media in children attending the first year of kindergarten. By randomization, 222 enrolled children attending the first year of kindergarten were divided into a treated group (N = 111) receiving for 6 months a daily treatment with BLIS K12 (Bactoblis®) and a control group (N = 111) who were monitored as untreated controls. During the 6 months of treatment and 3 months of follow-up, the children were evaluated for treatment tolerance, and for episodes of streptococcal pharyngo-tonsillitis, scarlet fever and acute otitis media. During the 6-month trial (N = 111 per group) the incidence of streptococcal pharyngo-tonsillitis, scarlet fever and acute otitis media was approximately 16%, 9% and 44% respectively in the treated group and 48%, 4% and 80% in the control group. During the 3-months follow-up (N = 29 per group) the corresponding rates of infection were 15%, 0% and 12% in the treated group and 26%, 6% and 36% in the controls. No apparent side effects were detected in the treated group either during treatment or follow-up. All of the enrolled children completed the study. The daily administration of BLIS K12 to children attending their first year of kindergarten was associated with a significant reduction in episodes of streptococcal pharyngitis and acute otitis media. No protection against scarlet fever was detected.

  18. Implementation of a cost-effective strategy to prevent neonatal early-onset group B haemolytic streptococcus disease in the Netherlands.

    Science.gov (United States)

    Kolkman, Diny G E; Rijnders, Marlies E B; Wouters, Maurice G A J; van den Akker-van Marle, M Elske; van der Ploeg, Cpb Kitty; de Groot, Christianne J M; Fleuren, Margot A H

    2013-07-30

    Early-onset Group B haemolytic streptococcus infection (EOGBS) is an important cause of neonatal morbidity and mortality in the first week of life. Primary prevention of EOGBS is possible with intra-partum antibiotic prophylaxis (IAP.) Different prevention strategies are used internationally based on identifying pregnant women at risk, either by screening for GBS colonisation and/or by identifying risk factors for EOGBS in pregnancy or labour. A theoretical cost-effectiveness study has shown that a strategy with IAP based on five risk factors (risk-based strategy) or based on a positive screening test in combination with one or more risk factors (combination strategy) was the most cost-effective approach in the Netherlands. IAP for all pregnant women with a positive culture in pregnancy (screening strategy) and treatment in line with the current Dutch guideline (IAP after establishing a positive culture in case of pre-labour rupture of membranes or preterm birth and immediate IAP in case of intra-partum fever, previous sibling with EOGBS or GBS bacteriuria), were not cost-effective. Cost-effectiveness was based on the assumption of 100% adherence to each strategy. However, adherence in daily practice will be lower and therefore have an effect on cost-effectiveness. The aims are to: a.) implement the current Dutch guideline, the risk-based strategy and the combination strategy in three pilot regions and b.) study the effects of these strategies in daily practice. Regions where all the care providers in maternity care implement the allocated strategy will be randomised. Before the introduction of the strategy, there will be a pre-test (use of the current guideline) involving 105 pregnant women per region. This will be followed by a post-test (use of the allocated strategy) involving 315 women per region. The outcome measures are: 1.) adherence to the specific prevention strategy and the determinants of adherence among care providers and pregnant women, 2.) outcomes

  19. Insulin gene mutations resulting in early-onset diabetes: marked differences in clinical presentation, metabolic status, and pathogenic effect through endoplasmic reticulum retention

    DEFF Research Database (Denmark)

    Meur, Gargi; Simon, Albane; Harun, Nasret

    2009-01-01

    OBJECTIVE: Heterozygous mutations in the human preproinsulin (INS) gene are a cause of nonsyndromic neonatal or early-infancy diabetes. Here, we sought to identify INS mutations associated with maturity-onset diabetes of the young (MODY) or nonautoimmune diabetes in mid-adult life, and to explore...... the molecular mechanisms involved. RESEARCH DESIGN AND METHODS: The INS gene was sequenced in 16 French probands with unexplained MODY, 95 patients with nonautoimmune early-onset diabetes (diagnosed at ... with early-onset diabetes whose clinical presentation is compatible with MODY. These led to the production of (pre)proinsulin molecules with markedly different trafficking properties and effects on ER stress, demonstrating a range of molecular defects in the beta-cell....

  20. Evidence for an agitated-aggressive syndrome in early-onset psychosis correlated with antisocial personality disorder, forensic history, and substance use disorder.

    Science.gov (United States)

    Huber, Christian G; Hochstrasser, Lisa; Meister, Klara; Schimmelmann, Benno G; Lambert, Martin

    2016-08-01

    Agitation, aggression, and violence are increased in psychotic disorders. Additionally, an earlier age at onset may be associated with aggressive behavior. However, the relationship of age at onset, an agitated-aggressive syndrome as measured with the Positive And Negative Syndrome Scale for Schizophrenia - Excited Component (PANSS-EC), and its potential correlates in first-episode psychosis (FEP) has not been studied. This study assessed the association between age at onset, an agitated-aggressive syndrome, and its potential correlates in a prospective sample of 52 FEP patients with early-onset and adult-onset followed up for 12months. Twenty-six patients conformed to the criteria of early-onset psychosis. Early age at onset was associated with antisocial personality disorder (p=0.004; φc=0.39), a history of legal involvement (p=0.005; φc=0.39), and higher rates of lifetime substance use disorder (SUD; p=0.002; φc=0.42). Early-onset patients had significantly higher PANSS-EC scores over the course of observation (F(1,44.4)=5.39; p=0.025; d=0.656), but no significant group differences emerged for the remaining PANSS subscores. PANSS-EC scores were correlated positively with antisocial personality disorder and forensic history at 6weeks, 3months, 6months, and 12months, and with lifetime substance use disorder at 3months and 6months. Patients with early onset psychosis may have increased levels of agitation/aggressiveness, and, more likely, antisocial personality disorder, forensic history, and lifetime substance use disorder. These variables were linked to suicidality, aggressiveness, and involuntary treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Rare variants of the 3’-5’ DNA exonuclease TREX1 in early onset small vessel stroke [version 1; referees: 2 approved

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    Sarah McGlasson

    2017-11-01

    Full Text Available Background: Monoallelic and biallelic mutations in the exonuclease TREX1 cause monogenic small vessel diseases (SVD. Given recent evidence for genetic and pathophysiological overlap between monogenic and polygenic forms of SVD, evaluation of TREX1 in small vessel stroke is warranted. Methods: We sequenced the TREX1 gene in an exploratory cohort of patients with lacunar stroke (Edinburgh Stroke Study, n=290 lacunar stroke cases. We subsequently performed a fully blinded case-control study of early onset MRI-confirmed small vessel stroke within the UK Young Lacunar Stroke Resource (990 cases, 939 controls. Results: No patients with canonical disease-causing mutations of TREX1 were identified in cases or controls. Analysis of an exploratory cohort identified a potential association between rare variants of TREX1 and patients with lacunar stroke. However, subsequent controlled and blinded evaluation of TREX1 in a larger and MRI-confirmed patient cohort, the UK Young Lacunar Stroke Resource, identified heterozygous rare variants in 2.1% of cases and 2.3% of controls. No association was observed with stroke risk (odds ratio = 0.90; 95% confidence interval, 0.49-1.65 p=0.74. Similarly no association was seen with rare TREX1 variants with predicted deleterious effects on enzyme function (odds ratio = 1.05; 95% confidence interval, 0.43-2.61 p=0.91. Conclusions: No patients with early-onset lacunar stroke had genetic evidence of a TREX1-associated monogenic microangiopathy. These results show no evidence of association between rare variants of TREX1 and early onset lacunar stroke. This includes rare variants that significantly affect protein and enzyme function. Routine sequencing of the TREX1 gene in patients with early onset lacunar stroke is therefore unlikely to be of diagnostic utility, in the absence of syndromic features or family history.

  2. Significant adverse reactions to long-acting gonadotropin-releasing hormone agonists for the treatment of central precocious puberty and early onset puberty

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    Ji Woo Lee

    2014-09-01

    Full Text Available PurposeLong-acting gonadotropin-releasing hormone agonists (GnRHa are commonly used to treat central precocious puberty (CPP in Korea. Although rare, there have been reports on the characteristic of adverse reactions of GnRHa in CPP among the Korean population. This study was intended to report on our clinical experience regarding significant adverse reactions to long-acting GnRHa in CPP and early onset puberty and to evaluate the prevalence rate of serious side effects.MethodsThis retrospective study included children with CPP and early onset puberty, who were administered monthly with long-acting GnRHa (leuprolide acetate, triptorelin acetate at the outpatient clinic of Department of Pediatrics, at Inha University Hospital, between January 2011 and December 2013. We analyzed the clinical characteristics of patients who experienced significant adverse reactions and evaluated the prevalence rate.ResultsSix serious side effects (0.9% were observed among total of 621 CPP and early onset puberty children with GnRHa therapy. The number of sterile abscess formation was four in three patients (4 events of 621. Anaphylaxis occurred in only one patient, and unilateral slipped capital femoral epiphysis (SCFE in another one patient. Anaphylaxis occurred after the 6th administration of the monthly depot triptorelin acetate. Unilateral SCFE developed in GnRHa therapy.ConclusionSterile abscess formation occurred in 0.6% of CPP and early onset puberty patients from the administration of a monthly depot GnRHa therapy. The occurrences of anaphylaxis and SCFE are extremely rare, but can have serious implications on patients. Clinicians should be aware of these potential adverse effects related to GnRHa therapy in CPP.

  3. Impaired 8-Hydroxyguanine Repair Activity of MUTYH Variant p.Arg109Trp Found in a Japanese Patient with Early-Onset Colorectal Cancer

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    Kazuya Shinmura

    2014-01-01

    Full Text Available Purpose. The biallelic inactivation of the 8-hydroxyguanine repair gene MUTYH leads to MUTYH-associated polyposis (MAP, which is characterized by colorectal multiple polyps and carcinoma(s. However, only limited information regarding MAP in the Japanese population is presently available. Since early-onset colorectal cancer (CRC is a characteristic of MAP and might be caused by the inactivation of another 8-hydroxyguanine repair gene, OGG1, we investigated whether germline MUTYH and OGG1 mutations are involved in early-onset CRC in Japanese patients. Methods. Thirty-four Japanese patients with early-onset CRC were examined for germline MUTYH and OGG1 mutations using sequencing. Results. Biallelic pathogenic mutations were not found in any of the patients; however, a heterozygous p.Arg19*  MUTYH variant and a heterozygous p.Arg109Trp MUTYH variant were detected in one patient each. The p.Arg19* and p.Arg109Trp corresponded to p.Arg5* and p.Arg81Trp, respectively, in the type 2 nuclear-form protein. The defective DNA repair activity of p.Arg5* is apparent, while that of p.Arg81Trp has been demonstrated using DNA cleavage and supF forward mutation assays. Conclusion. These results suggest that biallelic MUTYH or OGG1 pathogenic mutations are rare in Japanese patients with early-onset CRC; however, the p.Arg19* and p.Arg109Trp MUTYH variants are associated with functional impairments.

  4. Streptococcal toxic shock syndrome caused by Streptococcus suis serotype 2.

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    Jiaqi Tang

    2006-05-01

    Full Text Available BACKGROUND: Streptococcus suis serotype 2 (S. suis 2, SS2 is a major zoonotic pathogen that causes only sporadic cases of meningitis and sepsis in humans. Most if not all cases of Streptococcal toxic shock syndrome (STSS that have been well-documented to date were associated with the non-SS2 group A streptococcus (GAS. However, a recent large-scale outbreak of SS2 in Sichuan Province, China, appeared to be caused by more invasive deep-tissue infection with STSS, characterized by acute high fever, vascular collapse, hypotension, shock, and multiple organ failure. METHODS AND FINDINGS: We investigated this outbreak of SS2 infections in both human and pigs, which took place from July to August, 2005, through clinical observation and laboratory experiments. Clinical and pathological characterization of the human patients revealed the hallmarks of typical STSS, which to date had only been associated with GAS infection. Retrospectively, we found that this outbreak was very similar to an earlier outbreak in Jiangsu Province, China, in 1998. We isolated and analyzed 37 bacterial strains from human specimens and eight from pig specimens of the recent outbreak, as well as three human isolates and two pig isolates from the 1998 outbreak we had kept in our laboratory. The bacterial isolates were examined using light microscopy observation, pig infection experiments, multiplex-PCR assay, as well as restriction fragment length polymorphisms (RFLP and multiple sequence alignment analyses. Multiple lines of evidence confirmed that highly virulent strains of SS2 were the causative agents of both outbreaks. CONCLUSIONS: We report, to our knowledge for the first time, two outbreaks of STSS caused by SS2, a non-GAS streptococcus. The 2005 outbreak was associated with 38 deaths out of 204 documented human cases; the 1998 outbreak with 14 deaths out of 25 reported human cases. Most of the fatal cases were characterized by STSS; some of them by meningitis or severe

  5. PSEN1 L226F mutation in a patient with early-onset Alzheimer’s disease in Korea

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    Bagyinszky E

    2016-10-01

    Full Text Available Eva Bagyinszky,1,* Sun Ah Park,2,* Hyung Jun Kim,2 Seong Hye Choi,3 Seong Soo A An,1 SangYun Kim4 1Department of BioNano Technology, Gachon University, Seongnam-si, 2Department of Neurology, Soonchunhyang University Bucheon Hospital, Bucheon, 3Department of Neurology, Inha University School of Medicine, Incheon, 4Department of Neurology, Seoul National University College of Medicine & Neurocognitive Behavior Center, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea *These authors contributed equally to this work Abstract: In this study, we report a first 226leucine (Leu mutation to phenylalanine (Phe in (PSEN1, CTC>TTC, L226F in Asia from a Korean early-onset Alzheimer’s disease (EOAD patient. Polymerase chain reaction (PCR–single strand conformation polymorphism, sequencing, and in silico predictions were performed. Previously, L226F was reported in EOAD patients by Zekanowski et al and Gómez-Tortosa et al. Disease phenotypes appeared in their thirties, and family history was positive in both cases. In our patient, age of onset was similar (37 years of age, but the mutation seemed to be de novo, since no affected family member was found. This leucine to phenylalanine substitution may cause additional stresses inside the transmembrane region due to large aromatic side chain and increased hydrophobic interactions with hydrocarbon chains in the membrane and its binding partners. Clinical phenotype of the mutation was aggressive progression into neurodegeneration, resulting in rapid cognitive decline. One of the patients was initially diagnosed with frontotemporal dementia, but the diagnosis was revised to AD upon postmortem studies in which Aβ plaques were seen. A second mutation, L226R, was found for the L226 residue. Similar to L226F, the patient with L226R also developed the first symptoms in his 30s, but EOAD was diagnosed in his 40s. These findings suggested that L226 might be an important residue in PSEN1

  6. 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; Bombois, Stéphanie; Boutantin, Justine; Cassagnaud, Pascaline; Chen, Yaohua; Delbeuck, Xavier; Delmaire, Christine; Deramecourt, Vincent; Gele, Patrick; Houssein-Foucher, Claude; Jacquemont, Charlotte; Lebert, Florence; Lebouvier, Thibaud; Lopez, Renaud; Mackowiak, Marie-Anne; Maureille, Aurélien; Pasquier, Florence; Petyt, Grégory; Pollet, Marianne; Rollin-Sillaire, Adeline; Schraen, Susanna; Semah, Franck; Vanhoutte, Matthieu

    2017-01-01

    Background: 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. Objective: The objective of this study was to assess the putative association between VRFs and EOAD. Methods: 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. Results: 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). Conclusion: 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. PMID:28984595

  7. Construct Validity and Reliability of the SARA Gait and Posture Sub-scale in Early Onset Ataxia

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    Tjitske F. Lawerman

    2017-12-01

    Full Text Available Aim: In children, gait and posture assessment provides a crucial marker for the early characterization, surveillance and treatment evaluation of early onset ataxia (EOA. For reliable data entry of studies targeting at gait and posture improvement, uniform quantitative biomarkers are necessary. Until now, the pediatric test construct of gait and posture scores of the Scale for Assessment and Rating of Ataxia sub-scale (SARA is still unclear. In the present study, we aimed to validate the construct validity and reliability of the pediatric (SARAGAIT/POSTURE sub-scale.Methods: We included 28 EOA patients [15.5 (6–34 years; median (range]. For inter-observer reliability, we determined the ICC on EOA SARAGAIT/POSTURE sub-scores by three independent pediatric neurologists. For convergent validity, we associated SARAGAIT/POSTURE sub-scores with: (1 Ataxic gait Severity Measurement by Klockgether (ASMK; dynamic balance, (2 Pediatric Balance Scale (PBS; static balance, (3 Gross Motor Function Classification Scale -extended and revised version (GMFCS-E&R, (4 SARA-kinetic scores (SARAKINETIC; kinetic function of the upper and lower limbs, (5 Archimedes Spiral (AS; kinetic function of the upper limbs, and (6 total SARA scores (SARATOTAL; i.e., summed SARAGAIT/POSTURE, SARAKINETIC, and SARASPEECH sub-scores. For discriminant validity, we investigated whether EOA co-morbidity factors (myopathy and myoclonus could influence SARAGAIT/POSTURE sub-scores.Results: The inter-observer agreement (ICC on EOA SARAGAIT/POSTURE sub-scores was high (0.97. SARAGAIT/POSTURE was strongly correlated with the other ataxia and functional scales [ASMK (rs = -0.819; p < 0.001; PBS (rs = -0.943; p < 0.001; GMFCS-E&R (rs = -0.862; p < 0.001; SARAKINETIC (rs = 0.726; p < 0.001; AS (rs = 0.609; p = 0.002; and SARATOTAL (rs = 0.935; p < 0.001]. Comorbid myopathy influenced SARAGAIT/POSTURE scores by concurrent muscle weakness, whereas comorbid myoclonus predominantly influenced

  8. Mild angle early onset idiopathic scoliosis children avoid progression under FITS method (Functional Individual Therapy of Scoliosis).

    Science.gov (United States)

    Białek, Marianna

    2015-05-01

    Physiotherapy for stabilization of idiopathic scoliosis angle in growing children remains controversial. Notably, little data on effectiveness of physiotherapy in children with Early Onset Idiopathic Scoliosis (EOIS) has been published.The aim of this study was to check results of FITS physiotherapy in a group of children with EOIS.The charts of the patients archived in a prospectively collected database were retrospectively reviewed. The inclusion criteria were:diagnosis of EOIS based on spine radiography, age below 10 years, both girls and boys, Cobb angle between 118 and 308, Risser zero, FITS therapy, no other treatment (bracing), and a follow-up at least 2 years from the initiation of the treatment. The criterion for curve progression were as follows: the Cobb angle increase of 68 or more, for curve stabilization; the Cobb angle was 58 comparing to the initial radiograph,for curve correction; and the Cobb angle decrease of 68 or more at the final follow-up radiograph.There were 41 children with EOIS, 36 girls and 5 boys, mean age 7.71.3 years (range 4 to 9 years) who started FITS therapy. The curve pattern was single thoracic (5 children), single thoracolumbar (22 children) or double thoracic/thoracolumbar (14 children), totally 55 structural curvatures. The minimum follow-up was 2 years after initiation of the FITS treatment, maximum was 16 years, mean 4.8 years). At follow-up the mean age was 12.53.4 years. Out of 41 children, 10 passed pubertal growth spurt at the final follow-up and 31 were still immature and continued FITS therapy. Out of 41 children, 27 improved, 13 were stable, and one progressed. Out of 55 structural curves, 32 improved, 22 were stable and one progressed. For the 55 structural curves, the Cobb angle significantly decreased from 18.085.48 at first assessment to 12.586.38 at last evaluation,pphysiotherapy was effective in preventing curve progression in children with EOIS. Final postpubertal follow-up data is needed.

  9. Exome sequencing analysis reveals variants in primary immunodeficiency genes in patients with very early onset inflammatory bowel disease.

    Science.gov (United States)

    Kelsen, Judith R; Dawany, Noor; Moran, Christopher J; Petersen, Britt-Sabina; Sarmady, Mahdi; Sasson, Ariella; Pauly-Hubbard, Helen; Martinez, Alejandro; Maurer, Kelly; Soong, Joanne; Rappaport, Eric; Franke, Andre; Keller, Andreas; Winter, Harland S; Mamula, Petar; Piccoli, David; Artis, David; Sonnenberg, Gregory F; Daly, Mark; Sullivan, Kathleen E; Baldassano, Robert N; Devoto, Marcella

    2015-11-01

    Very early onset inflammatory bowel disease (VEO-IBD), IBD diagnosed at 5 years of age or younger, frequently presents with a different and more severe phenotype than older-onset IBD. We investigated whether patients with VEO-IBD carry rare or novel variants in genes associated with immunodeficiencies that might contribute to disease development. Patients with VEO-IBD and parents (when available) were recruited from the Children's Hospital of Philadelphia from March 2013 through July 2014. We analyzed DNA from 125 patients with VEO-IBD (age, 3 wk to 4 y) and 19 parents, 4 of whom also had IBD. Exome capture was performed by Agilent SureSelect V4, and sequencing was performed using the Illumina HiSeq platform. Alignment to human genome GRCh37 was achieved followed by postprocessing and variant calling. After functional annotation, candidate variants were analyzed for change in protein function, minor allele frequency less than 0.1%, and scaled combined annotation-dependent depletion scores of 10 or less. We focused on genes associated with primary immunodeficiencies and related pathways. An additional 210 exome samples from patients with pediatric IBD (n = 45) or adult-onset Crohn's disease (n = 20) and healthy individuals (controls, n = 145) were obtained from the University of Kiel, Germany, and used as control groups. Four hundred genes and regions associated with primary immunodeficiency, covering approximately 6500 coding exons totaling more than 1 Mbp of coding sequence, were selected from the whole-exome data. Our analysis showed novel and rare variants within these genes that could contribute to the development of VEO-IBD, including rare heterozygous missense variants in IL10RA and previously unidentified variants in MSH5 and CD19. In an exome sequence analysis of patients with VEO-IBD and their parents, we identified variants in genes that regulate B- and T-cell functions and could contribute to pathogenesis. Our analysis could lead to the

  10. Early-Onset X-Linked Retinitis Pigmentosa in a Heterozygous Female Harboring an Intronic Donor Splice Site Mutation in the Retinitis Pigmentosa GTPase Regulator Gene.

    Science.gov (United States)

    Shifera, Amde Selassie; Kay, Christine Nichols

    2015-01-01

    To report a heterozygous female presenting with an early-onset and severe form of X-linked retinitis pigmentosa (XLRP). This is a case series presenting the clinical findings in a heterozygous female with XLRP and two of her family members. Fundus photography, fundus autofluorescence, ocular coherence tomography, and visual perimetry are presented. The proband reported here is a heterozygous female who presented at the age of 8 years with an early onset and aggressive form of XLRP. The patient belongs to a four-generation family with a total of three affected females and four affected males. The patient was initially diagnosed with retinitis pigmentosa (RP) at the age of 4 years. Genetic testing identified a heterozygous donor splice site mutation in intron 1 (IVS1 + 1G > A) of the retinitis pigmentosa GTPase regulator gene. The father of the proband was diagnosed with RP when he was a young child. The sister of the proband, evaluated at the age of 6 years, showed macular pigmentary changes. Although carriers of XLRP are usually asymptomatic or have a mild disease of late onset, the proband presented here exhibited an early-onset, aggressive form of the disease. It is not clear why some carrier females manifest a severe phenotype. A better understanding of the genetic processes involved in the penetrance and expressivity of XLRP in heterozygous females could assist in providing the appropriate counseling to affected families.

  11. 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

  12. Streptococcal Pharyngitis and Appendicitis in Children.

    Science.gov (United States)

    Nielsen, Jason W; Abel, Stuart A; Kenney, Brian

    2018-01-01

    Several pathologies, including pharyngitis, are associated with abdominal pain that can mimic appendicitis. We sought to further understand the link between appendicitis-like symptoms and streptococcal (strep) pharyngitis. All patients undergoing ultrasound imaging for appendicitis in our emergency department during 2013 were reviewed (n = 1572). A total of 207 patients were identified who underwent both ultrasound for appendicitis and testing for strep pharyngitis. Demographic and outcomes data between rule out appendicitis patients who underwent strep testing and those who did not were compared. Strep testing was more common in younger patients (mean age = 8.26 vs 10.26 years P appendicitis and 35 (16.9%) patients tested positive for strep pharyngitis. No cases of concurrent strep pharyngitis and appendicitis were identified. The negative appendectomy rate in the strep pharyngitis tested group was 38.5% (5/13), compared with 7.7% (23/296) ( P = .003) in the nontested group. The appendicitis rate among the strep tested group was 3.8% (8/207) compared with 20% (273/1365) in the nontested group ( P appendicitis, and had a higher rate of negative appendectomy. A diagnosis of concurrent appendicitis and strep pharyngitis is rare. In cases of patients with sufficient symptoms to warrant testing for strep pharyngitis a diagnosis of appendicitis is less likely and surgical intervention leads to higher negative appendectomy rates.

  13. Synergistic inhibition of Streptococcal biofilm by ribose and xylitol.

    Science.gov (United States)

    Lee, Heon-Jin; Kim, Se Chul; Kim, Jinkyung; Do, Aejin; Han, Se Yeong; Lee, Bhumgey David; Lee, Hyun Ho; Lee, Min Chan; Lee, So Hui; Oh, Taejun; Park, Sangbin; Hong, Su-Hyung

    2015-02-01

    Streptococcus mutans and Streptococcus sobrinus are the major causative agents of human dental caries. Therefore, the removal or inhibition of these streptococcal biofilms is essential for dental caries prevention. In the present study, we evaluated the effects of ribose treatment alone or in combination with xylitol on streptococcal biofilm formation for both species. Furthermore, we examined the expression of genes responsible for dextran-dependent aggregation (DDAG). In addition, we investigated whether ribose affects the biofilm formation of xylitol-insensitive streptococci, which results from long-term exposure to xylitol. The viability of streptococci biofilms formed in a 24-well polystyrene plate was quantified by fluorescent staining with the LIVE/DEAD bacterial viability and counting kit, which was followed by fluorescence activated cell sorting analysis. The effects of ribose and/or xylitol on the mRNA expression of DDAG-responsible genes, gbpC and dblB, was evaluated by RT-qPCR. Our data showed that ribose and other pentose molecules significantly inhibited streptococcal biofilm formation and the expression of DDAG-responsible genes. In addition, co-treatment with ribose and xylitol decreased streptococcal biofilm formation to a further extent than ribose or xylitol treatment alone in both streptococcal species. Furthermore, ribose attenuated the increase of xylitol-insensitive streptococcal biofilm, which results in the reduced difference of biofilm formation between S. mutans that are sensitive and insensitive to xylitol. These data suggest that pentose may be used as an additive for teeth-protective materials or in sweets. Furthermore, ribose co-treatment with xylitol might help to increase the anti-cariogenic efficacy of xylitol. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Severe acute post-streptococcal glomerulonephritis in an infant

    Directory of Open Access Journals (Sweden)

    Jameela A Kari

    2013-01-01

    Full Text Available Acute post-streptococcal glomerulonephritis (APSGN is very rare below the age of two years. We report a 14-month-old girl who presented with frank hematuria and nephrotic syndrome following group A streptococcal pharyngitis (GAS, which was confirmed by laboratory investigations. The patient underwent a renal biopsy to confirm the diagnosis and was treated with prednisolone. The proteinuria and hematuria resolved completely in eight weeks. Our case demonstrates that APSGN should be considered in evaluating hematuria and nephrotic syndrome in infants and children below two years of age.

  15. T171. REDUCED FRONTAL CORTICAL THICKNESS AND SURFACE IN A 10 YEARS FOLLOW-UP OF EARLY ONSET PSYCHOSIS

    Science.gov (United States)

    Ilzarbe, Daniel; de la Serna, Elena; Baeza, Inmaculada; Pariente, Jose; Fortea, Adriana; Redondo, Marina; Bargallo, Nuria; Castro-Fornieles, Josefina; Sugranyes, Gisela

    2018-01-01

    Abstract Background Structural volume loss of cortical gray matter over time in schizophrenia has been widely reported (Vita et al. 2012), and may be more pronounced when the disorder has an onset prior to age 18 (Early Onset Psychosis, EOP; Arango et al. 2008). More recently, studies have focused on measures of cortical morphology. The single study in EOP so far has identified greater loss of cortical thickness (CTH) in patients with schizophrenia over time (van Haren et al. 2011), whereas to our knowledge, no so far study has examined measures of surface area (SA) in EOP following a longitudinal design. We set out to examine measures of both CTH and SA in a sample of EOP at 10-year-follow-up. Methods Patients with EOP were recruited at first episode, matched by sex and age with healthy controls (HC) and re-assessed at 10 years. Subjects were evaluated clinically and structural T1 volumes were acquired using magnetic resonance imaging at baseline and 10-year-follow-up. Images were preprocessed, segmented and analysed with FreeSurfer. Quality control procedure was carried out by two raters. Images were segmented and CTH and SA values were extracted for each parcellation employing Desikan-Killiany Atlas; these were grouped in frontal, occipital, temporal, parietal and cingulate lobes so as to reduce multiple comparisons. When group or group by time effects were detected, parcellations were individually examined. A linear mixed model was built using Stata IC 13.1 to evaluate the effect of group and time on CTH and SA, including hemisphere as fixed effects and correcting by total intracranial volume and setting a critical p-value of .05. Results Thirty-nine subjects completed the follow-up. After removing 9 due to poor quality T1 images (technical problems, excess of movement), 28 subjects were finally included (13 EOP, 15 HC). There were no significant differences in age (EOP=26.9 ± 0.6 vs HC=27.2 ± 0.3 at follow-up) or sex distribution (%female: EOP=43% vs HC=38

  16. Structure of a streptococcal adhesion carbohydrate receptor

    International Nuclear Information System (INIS)

    Cassels, F.J.; Fales, H.M.; London, J.; Carlson, R.W.; van Halbeek, H.

    1990-01-01

    Interactions between complementary protein and carbohydrate structures on different genera of human oral bacteria have been implicated in the formation of dental plaque. The carbohydrate receptor on Streptococcus sanguis H1 that is specific for the adhesion on Capnocytophaga ochracea ATCC 33596 has been isolated from the streptococcal cell wall, purified, and structurally characterized. The hexasaccharide repeating unit of the polysaccharide was purified by reverse-phase, amino-bonded silica, and gel permeation high performance liquid chromatography. Earlier studies established that the repeating unit was a hexasaccharide composed of rhamnose, galactose, and glucose in the ration of 2:3:1, respectively. In the present study, determination of absolute configuration by gas chromatography of the trimethylsilyl (+)-2-butyl glycosides revealed that the rhamnose residues were of the L configuration while the hexoses were all D. 252Californium plasma desorption mass spectrometry of the native, the acetylated and the reduced and acetylated hexasaccharide determined that the molecular mass of the native hexasaccharide was 959, and that the 2 rhamnose residues were linked to each other at the nonreducing terminus of the linear molecule. Methylation analysis revealed the positions of the glycosidic linkages in the hexasaccharide and showed that a galactose residue was present at the reducing end. The structural characterization of the hexasaccharide was completed by one and two dimensional 1H and 13C NMR spectroscopy. Complete 1H and 13C assignments for each glycosyl residue were established by two-dimensional (1H,1H) correlation spectroscopy, homonuclear Hartmann-Hahn, and (13C,1H) correlation experiments. The configurations of the glycosidic linkages were inferred from the chemical shifts and coupling constants of the anomeric 1H and 13C resonances

  17. Ca2+/nuclear factor of activated T cells signaling is enriched in early-onset rectal tumors devoid of canonical Wnt activation.

    Science.gov (United States)

    Kumar, Raju; Raman, Ratheesh; Kotapalli, Viswakalyan; Gowrishankar, Swarnalata; Pyne, Saumyadipta; Pollack, Jonathan R; Bashyam, Murali D

    2018-02-01

    Our previous extensive analysis revealed a significant proportion of early-onset colorectal tumors from India to be localized to the rectum in younger individuals and devoid of deregulated Wnt/β-catenin signaling. In the current study, we performed a comprehensive genome-wide analysis of clinically well-annotated microsatellite stable early-onset sporadic rectal cancer (EOSRC) samples. Results revealed extensive DNA copy number alterations in rectal tumors in the absence of deregulated Wnt/β-catenin signaling. More importantly, transcriptome profiling revealed a (non-Wnt/β-catenin, non-MSI) genetic signature that could efficiently and specifically identify Wnt- rectal cancer. The genetic signature included a significant representation of genes belonging to Ca 2+ /NFAT signaling pathways that were validated in additional samples. The validated NFAT target genes exhibited significantly higher expression levels than canonical Wnt/β-catenin targets in Wnt- samples, an observation confirmed in other CRC expression data sets as well. We confirmed the validated genes to be transcriptionally regulated by NFATc1 by (a) evaluating their respective transcript levels and (b) performing promoter-luciferase and chromatin immunoprecipitation assays following ectopic expression as well as knockdown of NFATc1 in CRC cells. NFATc1 and its targets RUNX2 and GSN could drive increased migration in CRC cells. Finally, the validated genes were associated with poor survival in the cancer genome atlas CRC expression data set. This study is the first comprehensive molecular characterization of EOSRC that appears to be driven by noncanonical tumorigenesis pathways. Early-onset sporadic rectal cancer exhibits DNA gain and loss without Wnt activation. Ca 2+ /NFAT signaling appears to be activated in the absence of Wnt activation. An eight-gene genetic signature distinguishes Wnt+ and Wnt- rectal tumors. NFAT and its target genes regulate tumorigenic properties in CRC cells.

  18. EVERREST prospective study: a 6-year prospective study to define the clinical and biological characteristics of pregnancies affected by severe early onset fetal growth restriction.

    Science.gov (United States)

    Spencer, Rebecca; Ambler, Gareth; Brodszki, Jana; Diemert, Anke; Figueras, Francesc; Gratacós, Eduard; Hansson, Stefan R; Hecher, Kurt; Huertas-Ceballos, Angela; Marlow, Neil; Marsál, Karel; Morsing, Eva; Peebles, Donald; Rossi, Carlo; Sebire, Neil J; Timms, John F; David, Anna L

    2017-01-23

    Fetal growth restriction (FGR) is a serious obstetric condition for which there is currently no treatment. The EVERREST Prospective Study has been designed to characterise the natural history of pregnancies affected by severe early onset FGR and establish a well phenotyped bio-bank. The findings will provide up-to-date information for clinicians and patients and inform the design and conduct of the EVERREST Clinical Trial: a phase I/IIa trial to assess the safety and efficacy of maternal vascular endothelial growth factor (VEGF) gene therapy in severe early onset FGR. Data and samples from the EVERREST Prospective Study will be used to identify ultrasound and/or biochemical markers of prognosis in pregnancies with an estimated fetal weight (EFW) economic impact; psychological impact; neonatal condition, progress and complications; and infant growth and neurodevelopment to 2 years of corrected age in surviving infants. Standardised longitudinal ultrasound measurements are performed, including: fetal biometry; uterine artery, umbilical artery, middle cerebral artery, and ductus venosus Doppler velocimetry; and uterine artery and umbilical vein volume blood flow. Samples of maternal blood and urine, amniotic fluid (if amniocentesis performed), placenta, umbilical cord blood, and placental bed (if caesarean delivery performed) are collected for bio-banking. An initial analysis of maternal blood samples at enrolment is planned to identify biochemical markers that are predictors for fetal or neonatal death. The findings of the EVERREST Prospective Study will support the development of a novel therapy for severe early onset FGR by describing in detail the natural history of the disease and by identifying women whose pregnancies have the poorest outcomes, in whom a therapy might be most advantageous. The findings will also enable better counselling of couples with affected pregnancies, and provide a valuable resource for future research into the causes of FGR. NCT02097667

  19. 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.

  20. DEAR1 is a dominant regulator of acinar morphogenesis and an independent predictor of local recurrence-free survival in early-onset breast cancer.

    Directory of Open Access Journals (Sweden)

    Steven T Lott

    2009-05-01

    Full Text Available Breast cancer in young women tends to have a natural history of aggressive disease for which rates of recurrence are higher than in breast cancers detected later in life. Little is known about the genetic pathways that underlie early-onset breast cancer. Here we report the discovery of DEAR1 (ductal epithelium-associated RING Chromosome 1, a novel gene encoding a member of the TRIM (tripartite motif subfamily of RING finger proteins, and provide evidence for its role as a dominant regulator of acinar morphogenesis in the mammary gland and as an independent predictor of local recurrence-free survival in early-onset breast cancer.Suppression subtractive hybridization identified DEAR1 as a novel gene mapping to a region of high-frequency loss of heterozygosity (LOH in a number of histologically diverse human cancers within Chromosome 1p35.1. In the breast epithelium, DEAR1 expression is limited to the ductal and glandular epithelium and is down-regulated in transition to ductal carcinoma in situ (DCIS, an early histologic stage in breast tumorigenesis. DEAR1 missense mutations and homozygous deletion (HD were discovered in breast cancer cell lines and tumor samples. Introduction of the DEAR1 wild type and not the missense mutant alleles to complement a mutation in a breast cancer cell line, derived from a 36-year-old female with invasive breast cancer, initiated acinar morphogenesis in three-dimensional (3D basement membrane culture and restored tissue architecture reminiscent of normal acinar structures in the mammary gland in vivo. Stable knockdown of DEAR1 in immortalized human mammary epithelial cells (HMECs recapitulated the growth in 3D culture of breast cancer cell lines containing mutated DEAR1, in that shDEAR1 clones demonstrated disruption of tissue architecture, loss of apical basal polarity, diffuse apoptosis, and failure of lumen formation. Furthermore, immunohistochemical staining of a tissue microarray from a cohort of 123 young

  1. 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

  2. Commentary on 'Behavioural and cognitive-behavioural group-based parenting programmes for early-onset conduct problems in children aged 3 to 12 years'.

    Science.gov (United States)

    Haroon, Munib

    2013-03-07

    This is a commentary on a Cochrane review, published in this issue of EBCH, first published as: Furlong M, McGilloway S, Bywater T, Hutchings J, Smith SM, Donnelly M. Behavioural and cognitive-behavioural group-based parenting programmes for early-onset conduct problems in children aged 3 to 12 years. Cochrane Database of Systematic Reviews 2012, Issue 2. Art. No.: CD008225. DoI: 10.1002/14651858.CD008225.pub2. Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

  3. Genome wide association (GWA study for early onset extreme obesity supports the role of fat mass and obesity associated gene (FTO variants.

    Directory of Open Access Journals (Sweden)

    Anke Hinney

    2007-12-01

    Full Text Available Obesity is a major health problem. Although heritability is substantial, genetic mechanisms predisposing to obesity are not very well understood. We have performed a genome wide association study (GWA for early onset (extreme obesity.a GWA (Genome-Wide Human SNP Array 5.0 comprising 440,794 single nucleotide polymorphisms for early onset extreme obesity based on 487 extremely obese young German individuals and 442 healthy lean German controls; b confirmatory analyses on 644 independent families with at least one obese offspring and both parents. We aimed to identify and subsequently confirm the 15 SNPs (minor allele frequency > or =10% with the lowest p-values of the GWA by four genetic models: additive, recessive, dominant and allelic. Six single nucleotide polymorphisms (SNPs in FTO (fat mass and obesity associated gene within one linkage disequilibrium (LD block including the GWA SNP rendering the lowest p-value (rs1121980; log-additive model: nominal p = 1.13 x 10(-7, corrected p = 0.0494; odds ratio (OR(CT 1.67, 95% confidence interval (CI 1.22-2.27; OR(TT 2.76, 95% CI 1.88-4.03 belonged to the 15 SNPs showing the strongest evidence for association with obesity. For confirmation we genotyped 11 of these in the 644 independent families (of the six FTO SNPs we chose only two representing the LD bock. For both FTO SNPs the initial association was confirmed (both Bonferroni corrected p<0.01. However, none of the nine non-FTO SNPs revealed significant transmission disequilibrium.Our GWA for extreme early onset obesity substantiates that variation in FTO strongly contributes to early onset obesity. This is a further proof of concept for GWA to detect genes relevant for highly complex phenotypes. We concurrently show that nine additional SNPs with initially low p-values in the GWA were not confirmed in our family study, thus suggesting that of the best 15 SNPs in the GWA only the FTO SNPs represent true positive findings.

  4. A Study on BRCA1/2 Mutations, Hormone Status and HER-2 Status in Korean Women with Early-onset Breast Cancer

    International Nuclear Information System (INIS)

    Choi, Doo Ho; Jin, So Young; Lee, Dong Wha; Kim, Eun Seog; Kim, Yong Ho

    2008-01-01

    Women with breast cancer diagnosed at an age of 40 years or younger have a greater prevalence of germline BRCA1 and BRCA2 mutations than the prevalence of women with breast cancer diagnosed at older ages. Several immunohistochemical characteristics have been identified in breast cancers from studies of Caucasian women with BRCA1/2 mutations having familial or early-onset breast cancers. The aim of this study is to determine whether early-onset breast cancer in BRCA1 or BRCA2 mutation carriers, who were not selected from a family history, could be distinguished by the use of immunohistochemical methods and could be distinguished from breast cancer in women of a similar age without a germline BRCA1 or BRCA2 mutation. We also analyzed the prognostic difference between BRCA1/2 related and BRCA1/2 non-related patients by the use of univariate and multivariate analysis. Breast cancer tissue specimens from Korean women with early-onset breast cancers were studied using a tumor tissue microarray. Immunohistochemical staining of estrogen receptor (ER), progesterone receptor (PR) and HER-2, as well as the histology and grade of these specimens, were compared. The prognostic impact of immunohistochemical and histological factors as well as the BRCA1/2 mutation status was investigated separately. There were 14 cases and 16 deleterious BRCA1/2 mutations among 101 patients tested. A family history (4/14) and bilateral breast cancers (3/9) were high risk factors for BRCA1/2 mutations. BRCA1/2- associated cancers demonstrated more expression of ER-negative (19.4% versus 5.1%, p=0.038) and HER-2 negative than BRCA1/2 negative tumors, especially for tumors with BRCA1 tumors The BRCA1/2 mutation rate for patients with triple negative tumors (negative expression of ER, PR and HER-2) was 24.2%. Tumor size, nodal status, and HER-2 expression status were significantly associated with disease free survival, as determined by univariate and multivariate analysis, but the BRCA1/2 status was

  5. Comparative study of cyclioxygenase-2 expression and HER-2/neu amplification in Korean and caucasian woman with early-onset breast carcinoma

    International Nuclear Information System (INIS)

    Choi, Doo Ho; Kim, Eun Seog; Kim, Yong Ho; Jin, So Young; Lee, Dong Wha; Haffty, Bruce G.

    2004-01-01

    The purpose of this work was to study the differences of cyclooxygenase (COX-2) expression between Korean and Caucasian patients with early-onset breast carcinoma by immunohistochemistry. The test were analyzed to find a correlation between COX-2 and other biomarkers including HER-2/neu amplification, because we previously reported that a significant difference had been found in the expression of HER-2/neu between the two races. Furthermore, we investigated prognostic significance of COX-2 in Korean patients. Sixty Korean women who were diagnosed breast carcinoma at 45 years old or younger and 60 Caucasian women with breast carcinoma were selected for this study. The median age of both groups was 37 years and tumor sizes were distributed evenly between the two group. Paraffin embedded blocks of primary tumor were processed for immunohistochemical staining of COX-2. The COX-2 expression was evaluated according to the percentage of positive cells and the intensity of staining. And the results were compared with the data of the previous studies to find correlation between COX-2 and other parameters and survival data. Proportion of the COX-2 expression in total patients was 27.6%. The percentage of tumors that stained positive for COX-2 in Korean and Caucasian women with early-onset breast carcinoma were 37.9% and 20.8%, respectively. The difference was statistically not significant (ρ 0.090). Expression of COX-2 was not associated with several clinicopathologic parameters including HER-2/neu overexpression, but negative estrogen receptor status was correlated with significance (ρ = 0.046). The 5 year disease free survival rate for patients with COX-2 expression was 67.9%, compared to 81.9% of the COX-2 negative patients and the result was statistically not significant. A significant difference was not found in the expression of COX-2 between the two groups of patients with early-onset breast carcinoma. And correlation between COX-2 and other parameters was not

  6. Increasing prevalence of group B streptococcal infection among pregnant women

    DEFF Research Database (Denmark)

    Petersen, Kathrine Birch; Johansen, Helle Krogh; Rosthoj, Susanne

    2014-01-01

    the Clinical Microbiology Database. Maternal data were obtained from a local database at the RH. RESULTS: In our cohort, a total of 638 (3.8%) women were diagnosed with GBS, 517 (81%) from urine, 92 (14%) from vaginal swabs and 29 (5%) from both. The overall rate of women colonised with GBS rose from 3......INTRODUCTION: Group B streptococci (GBS) can cause preterm delivery for women and sepsis and meningitis in infants younger than 90 days of age. The present retrospective cohort study determines the trend over time in the rates of GBS and in demographic risk factors for GBS among pregnant women...... delivering at Rigshospitalet (RH). MATERIAL AND METHODS: In the period from 2002 to 2010, a total of 33,616 women gave birth at the RH. Our cohort was defined as 16,587 (49%) women examined by 24,724 cultures. All microbiological requisitions from the Department of Obstetrics at RH were extracted from...

  7. The prevalence of asymptomatic group B streptococcal infection and ...

    African Journals Online (AJOL)

    ... to culture GBS and confirmation with biochemical tests and serological test were done. ... None of the isolates were resistant to erythromycin and sensitive to ... The GBS sensitivity pattern to penicillin was similar to those reported elsewhere.

  8. Toxoplasma gondii as a Risk Factor for Early-Onset Schizophrenia: Analysis of Filter Paper Blood Samples Obtained at Birth

    DEFF Research Database (Denmark)

    Mortensen, Preben Bo; Nørgaard-Pedersen, Bent; Waltoft, Berit Lindum

    2007-01-01

    BACKGROUND: Infections during fetal life or neonatal period, including infections with Toxoplasma gondii, may be associated with a risk for schizophrenia and other mental disorders. The objectives of this study were to study the association between serological markers for maternal and neonatal....... Patients included persons born in Denmark in 1981 or later followed up through 1999 with respect to inpatient or outpatient treatment for schizophrenia or related disorders (ICD-10 F2) or affective disorders (ICD-10 F3). RESULTS: Toxoplasma gondii immunoglobulin G (IgG) levels corresponding to the upper...

  9. Toxoplasma gondii as a Risk Factor for Early-Onset Schizophrenia: Analysis of Filter Paper Blood Samples Obtained at Birth

    DEFF Research Database (Denmark)

    Mortensen, Preben Bo; Nørgaard-Pedersen, Bent; Waltoft, Berit Lindum

    2006-01-01

    BACKGROUND: Infections during fetal life or neonatal period, including infections with Toxoplasma gondii, may be associated with a risk for schizophrenia and other mental disorders. The objectives of this study were to study the association between serological markers for maternal and neonatal....... Patients included persons born in Denmark in 1981 or later followed up through 1999 with respect to inpatient or outpatient treatment for schizophrenia or related disorders (ICD-10 F2) or affective disorders (ICD-10 F3). RESULTS: Toxoplasma gondii immunoglobulin G (IgG) levels corresponding to the upper...

  10. Culture-proven early-onset neonatal sepsis in Arab states in the Gulf region: two-year prospective study

    Directory of Open Access Journals (Sweden)

    Majeda S. Hammoud

    2017-02-01

    Conclusions: The incidence