Sample records for early onset periodontitis

  1. Association between HLA antigens and early onset periodontitis.

    PubMed

    Firatli, E; Kantarci, A; Cebeci, I; Tanyeri, H; Sönmez, G; Carin, M; Tuncer, O

    1996-06-01

    HLA-A, B, C and DR antigen frequencies were determined in a group of patients with juvenile periodontitis and rapidly progressive periodontitis. In juvenile periodontitis patients, HLA-A24 and DR4 were found at a significantly higher level than in the control group, and in rapidly progressive periodontitis patients, A9 and DR4 were found at a significantly higher level than the control group. The presence of these antigens gives evidence as to the susceptibility of various forms of early onset periodontitis. PMID:8811476

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

    SciTech Connect

    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.

  3. Early-onset Periodontitis in Morocco is Associated with the Highly Leukotoxic Clone of Actinobacillus actinomycetemcomitans

    Microsoft Academic Search

    D. Haubek; O.-K. Ennibi; K. Poulsen; S. Poulsen; N. Benzarti; M. Kilian

    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 schoolchildren. Of 217 plaque samples, 131 (60.4%) were culture-positive for A. actinomycetemcomitans. A total of 19 of these

  4. Clinical and laboratory studies on a patient with early onset periodontitis and her family members. A case report.

    PubMed

    Takahashi, K; Takigawa, M; Hara, H; Nagai, A; Takashiba, S; Nishimura, F; Chihara, T; Ohyama, H; Satoh, N; Kurihara, H

    1995-05-01

    Extensive clinical, microbiological, hematological, and immunological studies were performed on a patient with early onset periodontitis (EOP) and two other members of the family. The proband, a 27-year-old female, had early onset periodontitis and a high level of serum rheumatoid factors (RF) with no diagnosable medical disease. Her mother had lost all her teeth at the age of 50 because of advanced periodontitis, while her elder sister was unaffected by periodontitis. Neither the proband's periodontally-affected mother nor her unaffected sister exhibited a detectable level of RF. In this study, we examined: 1) serum immunoglobulin G (IgG) antibody titers against putative periodontal pathogenic bacteria; 2) peripheral neutrophil functions; 3) phenotypic analyses of peripheral lymphocyte subpopulations; and 4) peripheral lymphocyte functions (T cell proliferative activity, ability of cytokine [interleukin (IL)-2, tumor necrosis factor-alpha, interferon-gamma, IL-6 and IL-8] and IgG and IgM productivity). High antibody titers to Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Campylobacter rectus were detected in the sera of the proband, as were high serum antibody titers to P. gingivalis in the mother and to C. rectus in the unaffected sister compared to the non-periodontitis affected subjects. The proband also showed enhanced neutrophil chemotaxis; a high percentage of pan-B cells; and high productivity of IL-6, IgG, and IgM compared to individuals who were not periodontally affected. The mother showed slightly low helper/induced T cells (Th/i) suppressor/cytotoxic T cells (Ts/c) ratios due to the elevated count of Ts/c, and high IFN-gamma productivity compared to control subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7623261

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

    PubMed

    Haubek, D; Ennibi, O K; Poulsen, K; Poulsen, S; Benzarti, N; Kilian, M

    2001-06-01

    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 schoolchildren. Of 217 plaque samples, 131 (60.4%) were culture-positive for A. actinomycetemcomitans. A total of 19 of these isolates had a 530-bp deletion in the leukotoxin promoter region characteristic of the JP2 clone. A strong association between the presence of A. actinomycetemcomitans with the 530-bp deletion and EOP was found (adjusted OR = 29.4; 95% Cl = 8.3 - 104.4; p < 0.0005), while no association could be demonstrated between the presence of A. actinomycetemcomitans without the deletion and EOP (adjusted OR = 1.3; 95% CI = 0.5 -2.9; p = 0.750). The study demonstrates that the endemic presence, in a human population, of the highly leukotoxic JP2 clone may result in an unusually high prevalence of EOP. PMID:11499517

  6. Early onset neonatal sepsis

    Microsoft Academic Search

    Betty Chacko; Inderpreet Sohi

    2005-01-01

    Objective: To study the maternal risk factors and clinico-bacteriological profile of early onset sepsis (EOS), in a tertiary care neonatal\\u000a unit.Methods: Relevant data of neonates born during the study period were obtained from their case records. A diagnosis of early onset\\u000a sepsis was made if either clinical sepsis developed within 72 hours of life or if positive blood\\/CSF cultures were

  7. Role of Treponema Denticola in Periodontal Diseases

    Microsoft Academic Search

    Michael N. Sela

    2001-01-01

    Among periodontal anaerobic pathogens, the oral spirochetes, and especially Treponema denticola, have been associated with periodontal diseases such as early-onset periodontitis, necrotizing ulcerative gingivitis, and acute pericoronitis. Basic research as well as clinical evidence suggest that the prevalence of T. denticola, together with other proteolytic Gram-negative bacteria in high numbers in periodontal pockets, may play an important role in the

  8. Early-Onset Neonatal Sepsis

    PubMed Central

    Simonsen, Kari A.; Anderson-Berry, Ann L.; Delair, Shirley F.

    2014-01-01

    SUMMARY Early-onset sepsis remains a common and serious problem for neonates, especially preterm infants. Group B streptococcus (GBS) is the most common etiologic agent, while Escherichia coli is the most common cause of mortality. Current efforts toward maternal intrapartum antimicrobial prophylaxis have significantly reduced the rates of GBS disease but have been associated with increased rates of Gram-negative infections, especially among very-low-birth-weight infants. The diagnosis of neonatal sepsis is based on a combination of clinical presentation; the use of nonspecific markers, including C-reactive protein and procalcitonin (where available); blood cultures; and the use of molecular methods, including PCR. Cytokines, including interleukin 6 (IL-6), interleukin 8 (IL-8), gamma interferon (IFN-?), and tumor necrosis factor alpha (TNF-?), and cell surface antigens, including soluble intercellular adhesion molecule (sICAM) and CD64, are also being increasingly examined for use as nonspecific screening measures for neonatal sepsis. Viruses, in particular enteroviruses, parechoviruses, and herpes simplex virus (HSV), should be considered in the differential diagnosis. Empirical treatment should be based on local patterns of antimicrobial resistance but typically consists of the use of ampicillin and gentamicin, or ampicillin and cefotaxime if meningitis is suspected, until the etiologic agent has been identified. Current research is focused primarily on development of vaccines against GBS. PMID:24396135

  9. Genetics Home Reference: Early-onset glaucoma

    MedlinePLUS

    ... pressure (hypertension) and diabetes mellitus, as well as family history. The risk of early-onset glaucoma depends mainly on heredity. Structural abnormalities that impede fluid drainage in the eye may ...

  10. Childhood Onset Schizophrenia and Early Onset Schizophrenia spectrum disorders

    PubMed Central

    Driver, David I.; Gogtay, Nitin; Rapoport, Judith L.

    2013-01-01

    Synopsis The clinical severity, impact on development, and poor prognosis of Childhood Onset Schizophrenia (COS) may represent a more homogeneous group. Positive symptoms in children are necessary for the diagnosis and hallucinations are more often multi modal. Both in healthy children, as well as in children with a variety of other psychiatric illnesses, hallucinations are not uncommon [1] and diagnosis should not be based on these alone. COS is an extraordinarily rare illness which is poorly understood but appears continuous with the adult onset disorder. Additionally, as seen in other areas of medicine, early onset populations have more prominent progressive brain changes, and genetic risk factors [2]. Diagnosing a child with schizophrenia has profound effects on the treatment course, including the potential for neglecting another disorder, as psychosis often becomes the primary focus. Since onset is almost always insidious, the “episodes” so common in later onset disorder are rarely seen. The gold standard for diagnosis remains the use of unmodified DSM criteria, based on extensive collateral information. Once a diagnosis is affirmed, aggressive medication treatment, in majority of cases with Clozapine, combined with family education and individual counseling may defer further deterioration. PMID:24012072

  11. Early onset (childhood) monogenic neuropathies.

    PubMed

    Landrieu, Pierre; Baets, Jonathan

    2013-01-01

    Hereditary neuropathies (HN) with onset in childhood are categorized according to clinical presentation, pathogenic mechanism based on electrophysiology, genetic transmission and, in selected cases, pathological findings. Especially relevant to pediatrics are the items "secondary" versus "primary" neuropathy, "syndromic versus nonsyndromic," and "period of life." Different combinations of these parameters frequently point toward specific monogenic disorders. Ruling out a neuropathy secondary to a generalized metabolic disorder remains the first concern in pediatrics. As a rule, metabolic diseases include additional, orienting symptoms or signs, and their biochemical diagnosis is based on logical algorithms. Primary, motor sensory are the most frequent HN and are dominated by demyelinating autosomal dominant (AD) forms (CMT1). Other forms include demyelinating autosomal recessive (AR) forms, axonal AD/AR forms, and forms with "intermediate" electrophysiological phenotype. Peripheral motor neuron disorders are dominated by AR SMN-linked spinal muscular atrophies. (Distal) hereditary motor neuropathies represent <10% of HN but exhibit large clinical and genetic heterogeneity. Sensory/dysautonomic HN involves five classic subtypes, each one related to specific genes. However, genetic heterogeneity is larger than initially suspected. Syndromic HN distinguish "purely neurological syndromes", which are multisystemic, such as spinocerebellar atrophies +, spastic paraplegias +, etc. Peripheral neuropathy is possibly the presenting feature, including in childhood. Autosomal recessive forms, on average, start more frequently in childhood. "Multiorgan syndromes", on the other hand, are more specific to Pediatrics. AR forms, which are clearly degenerative, prompt the investigation of a large set of pleiotropic genes. Other syndromes expressed in the perinatal period are mainly developmental disorders, and can sometimes be related to specific transcription factors. Systematic malformative workup and ethical considerations are necessary. Altogether, >40 genes with various biological functions have been found to be responsible for primary HN. Many are responsible for various phenotypes, including some without the polyneuropathic trait, and some for various types of transmission. PMID:23931819

  12. THE LINK BETWEEN EARLY ONSET DRINKING AND EARLY ONSET ALCOHOL-IMPAIRED DRIVING IN YOUNG MALES

    PubMed Central

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

    2014-01-01

    Background Young drivers represent a disproportionate number of the individuals involved in alcohol-impaired driving. Although there is a known association between drinking and alcohol-impaired driving in young drivers, the link between early onset drinking and early onset alcohol-impaired driving has not been explored. Objectives The present study aimed to assess this link along with potentially confounding factors. Methods The assessment used a proportional hazards model with data collected from the Buffalo Longitudinal Study of Young Men, a population based sample of 625 males at ages of 16–19 years old. Results Controlling for the effects of potentially relevant confounds, the early onset of drinking was the most influential factor in predicting the early onset of alcohol-impaired driving. Race and the early onset of other forms of delinquency also played a significant role in the early onset of alcohol-impaired driving. Conclusion Preventing an early start of drinking among adolescents may be the most critical factor to address in preventing an early start of alcohol-impaired driving. PMID:24766089

  13. Periodontal Disease and the Oral Microbiota in New-Onset Rheumatoid Arthritis

    PubMed Central

    Scher, Jose U.; Ubeda, Carles; Equinda, Michele; Khanin, Raya; Buischi, Yvonne; Viale, Agnes; Lipuma, Lauren; Attur, Mukundan; Pillinger, Michael H.; Weissmann, Gerald; Littman, Dan R.; Pamer, Eric G.; Bretz, Walter A.; Abramson, Steven B.

    2012-01-01

    Objective To profile the subgingival oral microbiota abundance and diversity in never-treated, new-onset rheumatoid arthritis (NORA) patients. Methods Periodontal disease (PD) status, clinical activity and sociodemographic factors were determined in patients with NORA, chronic RA (CRA) and healthy subjects. Massively parallel pyrosequencing was used to compare the composition of subgingival microbiota and establish correlations between presence/abundance of bacteria and disease phenotypes. Anti-P. gingivalis antibodies were tested to assess prior exposure. Results The more advanced forms of periodontitis are already present at disease onset in NORA patients. The subgingival microbiota of NORA is distinct from controls. In most cases, however, these differences can be attributed to PD severity and are not inherent to RA. The presence and abundance of P. gingivalis is directly associated with PD severity as well, is not unique to RA, and does not correlate with anti-citrullinated peptide antibody (ACPA) titers. Overall exposure to P. gingivalis is similar in RA and controls, observed in 78.4% and 83.3%, respectively. Anaeroglobus geminatus correlated with ACPA/RF presence. Prevotella and Leptotrichia species are the only characteristic taxa in the NORA group irrespective of PD status. Conclusions NORA patients exhibit a high prevalence of PD at disease onset, despite their young age and paucity of smoking history. The subgingival microbiota of NORA patients is similar to CRA and healthy subjects of comparable PD severity. Although colonization with P. gingivalis correlates with PD severity, overall exposure is similar among groups. The role of A. geminatus and Prevotella/Leptotrichia species in this process merits further study. PMID:22576262

  14. Genomic insights into early-onset obesity

    PubMed Central

    2010-01-01

    The biological causes of childhood obesity are complex. Environmental factors, such as massive marketing campaigns for food leading to over-nutrition and snacking and the decline in physical activity, have undoubtedly contributed to the increased prevalence of overweight and obesity in children, but these cannot be considered as the only causes. Susceptibility to obesity is also determined to a great extent by genetic factors. Furthermore, molecular mechanisms involved in the regulation of gene expression, such as epigenetic mechanisms, can increase the risk of developing early-onset obesity. There is evidence that early-onset obesity is a heritable disorder, and a range of genetic factors have recently been shown to cause monogenic, syndromic and polygenic forms of obesity, in some cases interacting with environmental exposures. Modifications of the transcriptome can lead to increased adiposity, and the gut microbiome has recently been shown to be key to the genesis of obesity. These new genomic discoveries complement previous knowledge on the development of early-onset obesity and provide new perspectives for research on the complex molecular and physiological mechanisms involved in this disease. Personalized preventive strategies and genomic medicine may become possible in the near future. PMID:20587078

  15. Periodontal diseases: epidemiology.

    PubMed

    Papapanou, P N

    1996-11-01

    1. The interpretation of epidemiological data of periodontal disease is difficult, due to inconsistencies in the methodology used. It is not possible, therefore, to accurately assess if the prevalence of the periodontal diseases shows a world-wide decline. As long as the disease is assessed through accumulated clinical attachment loss, retention of the natural dentition in older ages entails increased prevalence in these cohorts. Contemporary epidemiological studies should ideally employ full-mouth examination of the periodontal tissues. Partial recording estimates are generally biased, especially when the prevalence of the disease is low. 2. Early-onset periodontitis is infrequent in all populations. Adult periodontitis is rather prevalent; however, advanced disease affects limited subfractions of the population (probably less than 10 to 15%). Although prevalence figures vary with race and geographic region, in most cases, the progression pattern of the disease seems compatible with the retention of a functional dentition throughout life. 3. Of a plethora of behavioral and environmental risk markers identified by multi-variate analysis, smoking and presence of certain subgingival microorganisms have been proven to be true risk factors. The same holds true for diabetes mellitus, a systemic condition that confers a risk for periodontal disease which is independent of the effect of other significant factors. 4. In certain cases, periodontal infections appear to have a systemic impact on the host. Most recent data indicate that periodontal disease may confer risk for coronary heart disease and pre-term low birth weight. PMID:9118256

  16. Differential clinical features of early-onset panic disorder

    Microsoft Academic Search

    J Segu??; M Márquez; L Garc??a; J Canet; L Salvador-Carulla; M Ortiz

    1999-01-01

    Background: Although panic disorder (PD) begins typically in adulthood, an earlier onset is not uncommon. Recent studies on early-onset PD indicate that this subgroup of patients may display distinct clinical characteristics. Objective: To compare a subgroup of early-onset PD patients with the rest of the sample. Method: A consecutive series of 442 patients with PD were included. Family histories were

  17. Impaired Phagocytosis in Localized Aggressive Periodontitis: Rescue by Resolvin E1

    Microsoft Academic Search

    Gabrielle Fredman; Sungwhan F. Oh; Srinivas Ayilavarapu; Hatice Hasturk; Charles N. Serhan; Thomas E. van Dyke; Dominik Hartl

    2011-01-01

    Resolution of inflammation is an active temporally orchestrated process demonstrated by the biosynthesis of novel proresolving mediators. Dysregulation of resolution pathways may underlie prevalent human inflammatory diseases such as cardiovascular diseases and periodontitis. Localized Aggressive Periodontitis (LAP) is an early onset, rapidly progressing form of inflammatory periodontal disease. Here, we report increased surface P-selectin on circulating LAP platelets, and elevated

  18. Periodontal management in orthognathic surgery: early screening of periodontal risk and its current management for the optimization of orthodontic and surgical treatments.

    PubMed

    Straub, B; Bouletreau, P; Breton, P

    2014-09-01

    Orthodontic preparation for orthognathic surgery requires correcting mal-occlusions and coordination of arcades. In addition to improving the aesthetics, these treatments can ensure the achievement and sustainability of prosthetics and/or implants. Nevertheless, periodontal structures are easily damaged. Orthodontic displacement can only be applied in the absence of inflammation or weakened periodontal structure. An early detection of periodontal risk should be achievable by prescribers of a surgical-orthodontic treatment. Simplified periodontal examination, with easily detectable warning signs, will help to identify the periodontal risk. Although periodontal treatment follows current "non invasive" trend, some procedures remain necessary to prevent and/or remedy periodontal defects or diseases, such as mineral periodontal reinforcement corticotomy. It is essential that the patient meets all the practitioners to plan and assess the extent of the constraints necessary to optimize results, before starting orthodontic treatment combined with orthognathic surgery. Any periodontal complication (even minor) will be considered as a failure, regardless of good aesthetic and functional results. PMID:25017293

  19. [Periodontal management in orthognathic surgery: early screening of periodontal risk and its current management for the optimization of orthodontic and surgical treatments].

    PubMed

    Straub, B; Bouletreau, P; Breton, P

    2014-09-01

    Orthodontic preparation for orthognathic surgery requires correcting malocclusions and coordination of arcades. In addition to improving the aesthetics, these treatments can ensure the achievement and sustainability of prosthetics and/or implants. Nevertheless periodontal structures are easily damaged. Orthodontic displacement can only be applied in the absence of inflammation or weakened periodontal structures. An early detection of periodontal risk should be achievable by prescribers of a surgical-orthodontic treatment. Simplified periodontal examination, with easily detectable warning signs, will help identify the periodontal risk. Although periodontal treatment follows current "non-invasive" trend, some procedures remain necessary to prevent and/or remedy periodontal defects or diseases, such as mineral periodontal reinforcement based on corticotomy principles. It is essential that the patient meet all the practitioners to plan and assess the extent of the constraints necessary to optimize results, before starting orthodontic treatment combined with orthognathic surgery. Any periodontal complication (even minor) will be considered as a failure, regardless of good aesthetic and functional results. PMID:25017292

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

    PubMed

    Sansone, Randy A; Sansone, Lori A

    2009-11-01

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

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

    Microsoft Academic Search

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

    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 controlled intervention trial, we examined whether intervention-induced reductions in ADHD symptoms at age 9 mediated the reduced risk of tobacco use

  2. DIVERGENT CANCER PATHWAYS FOR EARLY-ONSET AND LATE-ONSET CUTANEOUS MALIGNANT MELANOMA

    PubMed Central

    Pfeiffer, Ruth M.; Tucker, Margaret A.; Rosenberg, Philip S.

    2009-01-01

    Background Emerging data suggest that cutaneous malignant melanomas (CMM) may arise through divergent cancer pathways, linked to intermittent versus accumulated sun exposure. However, numerous questions remain regarding the timing and/or age of exposure. Methods We, therefore, systematically examined the effect of aging upon CMM incidence in the Surveillance, Epidemiology, and End Results program of the National Cancer Institute. Standard descriptive epidemiology was supplemented with mathematical models. The impact of advancing age upon CMM incidence was assessed by gender, histopathological classification (superficial spreading melanoma (SSM) or lentigo maligna melanoma (LMM)), and anatomic site (face, head, and neck (FHN) or lower extremity (LE)). Results Gender, histopathology, and anatomic site were age-specific effect modifiers for CMM, showing divergent (bimodal) early- and late-onset cancer pathways. Early-onset melanomas were predominantly associated with female gender, SSM, and LE. Late-onset melanomas were correlated with male gender, LMM, and FHN. Early- and late-onset melanoma populations were confirmed with age-period-cohort models that were adjusted for period and cohort effects. Two-component mixture models also fit the data better than a single cancer population. Conclusions These results are consistent with a divergent and age-dependent solar hypothesis for CMM. Early-onset melanomas may represent gene-sun exposure interactions occurring early (and/or intermittently) in life among susceptible individuals. Late-onset melanomas possibly reflect accumulated lifelong sun exposure in comparatively less susceptible individuals. Future analytical studies should be adequately powered to account for this age-dependent effect modification for acknowledged (gender, histopathology, and anatomic site) as well as suspected melanoma risk factors such as constituent genetic variants. PMID:19536874

  3. Early identification of 'acute-onset' chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Sung, Jia-Ying; Tani, Jowy; Park, Susanna B; Kiernan, Matthew C; Lin, Cindy Shin-Yi

    2014-08-01

    Distinguishing patients with acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy prior to relapse is often challenging at the onset of their clinical presentation. In the present study, nerve excitability tests were used in conjunction with the clinical phenotype and disease staging, to differentiate between patients with acute-onset chronic inflammatory demyelinating polyneuropathy and patients with acute inflammatory demyelinating polyneuropathy at an early stage, with the aim to better guide treatment. Clinical assessment, staging and nerve excitability tests were undertaken on patients initially fulfilling the diagnostic criteria of acute inflammatory demyelinating polyneuropathy soon after symptom onset and their initial presentation. Patients were subsequently followed up for minimum of 12 months to determine if their clinical presentations were more consistent with acute-onset chronic inflammatory demyelinating polyneuropathy. Clinical severity as evaluated by Medical Research Council sum score and Hughes functional grading scale were not significantly different between the two cohorts. There was no difference between the time of onset of initial symptoms and nerve excitability test assessment between the two cohorts nor were there significant differences in conventional nerve conduction study parameters. However, nerve excitability test profiles obtained from patients with acute inflammatory demyelinating polyneuropathy demonstrated abnormalities in the recovery cycle of excitability, including significantly reduced superexcitability (P < 0.001) and prolonged relative refractory period (P < 0.01), without changes in threshold electrotonus. In contrast, in patients with acute-onset chronic inflammatory demyelinating polyneuropathy, a different pattern occurred with the recovery cycle shifted downward (increased superexcitability, P < 0.05; decreased subexcitability, P < 0.05) and increased threshold change in threshold electrotonus in both hyperpolarizing and depolarizing directions [depolarizing threshold electrotonus (90-100 ms) P < 0.005, hyperpolarizing threshold electrotonus (10-20 ms), P < 0.01, hyperpolarizing threshold electrotonus (90-100 ms), P < 0.05], perhaps suggesting early hyperpolarization. In addition, using excitability parameters superexcitability, subexcitability and hyperpolarizing threshold electrotonus (10-20 ms), the patients with acute inflammatory demyelinating polyneuropathy and acute-onset chronic inflammatory demyelinating polyneuropathy could be clearly separated into two non-overlapping groups. Studies of nerve excitability may be able to differentiate acute from acute-onset chronic inflammatory demyelinating polyneuropathy at an early stage. Characteristic nerve excitability parameter changes occur in early acute-onset chronic inflammatory demyelinating polyneuropathy, to match the clinical phenotype. Importantly, this pattern of change was strikingly different to that shown by patients with acute inflammatory demyelinating polyneuropathy, suggesting that nerve excitability techniques may be useful in distinguishing acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy at the initial stage. PMID:24983276

  4. Association between Periodontitis and Alzheimer's Disease

    PubMed Central

    Abbayya, Keshava; Puthanakar, Nagraj Y; Naduwinmani, Sanjay; Chidambar, Y S

    2015-01-01

    Alzheimer's disease (AD) is a neurodegenerative disease which significantly increases with age. Its onset can be either early or late. AD is characterized by the salient inflammatory features, microglial activation, and increased levels of proinflammatory cytokines which contribute to the inflammatory status of the central nervous system (CNS). Whereas, periodontitis is a common oral infection associated with the gram negative anaerobic bacteria. Periodontitis can be marked as a “low-grade systemic disease” by release of proinflammatory cytokines into systemic circulation and elevation of C-reactive protein (CRP). Inflammation is known to play a pivotal role in both the disease process serving as a connecting link between periodontitis and AD. The present review throws a light on possible enigmatic link between AD and periodontitis. This review is designed by collecting data from PubMed database using key words like “Alzheimer's disease”, “inflammation”, “periodontitis”, and “proinflammatory cytokines”. PMID:26199919

  5. Early and Late Onset Sepsis in Late Preterm Infants

    PubMed Central

    Cohen-Wolkowiez, Michael; Moran, Cassandra; Benjamin, Daniel K.; Cotten, C. Michael; Clark, Reese H.; Benjamin, Daniel K.; Smith, P. Brian

    2009-01-01

    Background Preterm birth is increasing worldwide, and late preterm births, which comprise more than 70% of all preterm births, account for much of the increase. Early and late onset sepsis results in significant mortality in extremely preterm infants, but little is known about sepsis outcomes in late preterm infants. Methods This is an observational cohort study of infants < 121 days of age (119,130 infants less than or equal to 3 days of life and 106,142 infants between 4 and 120 days of life) with estimated gestational age at birth between 34 and 36 weeks, admitted to 248 neonatal intensive care units in the United States between 1996 and 2007. Results During the study period, the cumulative incidence of early and late onset sepsis was 4.42 and 6.30 episodes per 1000 admissions, respectively. Gram-positive organisms caused the majority of early and late onset sepsis episodes. Infants with early onset sepsis caused by Gram-negative rods and infants with late onset sepsis were more likely to die than their peers with sterile blood cultures (OR 4.39, 95% CI 1.71–11.23, P=0.002; and OR 3.37, 95% CI 2.35–4.84, P<0.001, respectively). Conclusion Late preterm infants demonstrate specific infection rates, pathogen distribution, and mortality associated with early and late onset sepsis. The results of this study are generalizable to late preterm infants admitted to the special care nursery or neonatal intensive care unit. PMID:19953725

  6. Early life environmental predictors of asthma age-of-onset.

    PubMed

    Ferry, Olivia R; Duffy, David L; Ferreira, Manuel A R

    2014-11-01

    Prevention strategies that delay the onset of asthma may improve clinical outcomes. To identify early life environmental exposures associated with asthma age-of-onset and potential genetic modifiers of these exposures, we studied 1085 subjects with physician-diagnosed asthma and disease onset at or after age two. Subjects reported retrospectively on their exposure to 17 environmental factors before the age of two. The presence of individual or combinations of these early life exposures was then tested for association with variation in asthma age-of-onset. For exposures significantly associated with age-of-onset, we tested if 26 single nucleotide polymorphisms (SNP) with an established association with allergic disease significantly modified the effect of the exposure. Five environmental exposures were significantly associated with variation in asthma age-of-onset after correction for multiple testing: carpet at home (P?=?6?×?10(-5)), a serious chest illness (P?=?10(-4)), father a cigarette smoker (P?=?6?×?10(-4)) and direct exposure to father's smoking (P?=?3?×?10(-4)). Individuals with early childhood asthma onset, between the ages of two and six, were 1.4-fold (CI 1.1-1.9) more likely to report having lived in a house with carpet and 2.1-fold (CI 1.3-3.5) more likely to report suffering a serious chest illness before the age of two, than asthmatics with later disease onset. We further found these individual risks to increase to 3.2-fold (CI 1.7-6.0) if carpet exposure and suffering a serious chest illness co-occurred before age two. Paternal smoking exposures were less likely to be reported by asthmatics with early when compared to later disease onset (OR 0.5, CI 0.3-0.7). There were no significant SNP interactions with these environmental exposures after correction for multiple testing. Our results suggest that disease onset in individuals at a high-risk of developing asthma can potentially be delayed by avoiding exposure to carpet at home and preventing serious chest illnesses during the first 2 years of life. PMID:25505548

  7. Increased developmental deviance and premorbid dysfunction in early onset schizophrenia.

    PubMed

    Vourdas, Apostolos; Pipe, Roderic; Corrigall, Richard; Frangou, Sophia

    2003-07-01

    Abnormal neurodevelopment and poor premorbid function have been described in schizophrenia. It is unclear whether abnormalities in these domains are increased in patients with early onset schizophrenia (EOS; onset before the 18th birthday) and whether they act to precipitate the earlier onset of the disorder. To address these questions, we collected information based on maternal interviews about the premorbid function of 40 adolescents with recent onset schizophrenia and an equal number of healthy controls using the Developmental Scale Score, the Premorbid Schizoid and Schizotypal Trait Scale (PSST) and Premorbid Adjustment Scale (PAS). Data on the PSST and PAS were also available in 54 patients with adult onset schizophrenia (AOS; onset after the 20th birthday). Compared to healthy controls, EOS patients had (a). delayed speech milestones, difficulties in reading and spelling and greater overall developmental deviance; (b). poor premorbid adjustment in childhood, which became even more deviant in adolescence particularly in boys and (c). more schizophrenia spectrum traits. Both premorbid adjustment and personality traits were more abnormal in patients with increased developmental deviance suggesting the possibility that they represent different manifestations of ongoing abnormalities in developmental processes. EOS patients had more impaired premorbid adjustment in adolescence and schizophrenia spectrum traits compared to AOS cases. Age of onset was related to developmental deviance, premorbid schizophrenia spectrum traits and childhood adjustment in EOS patients only. PMID:12765738

  8. Treatment of Early Onset Hair Pulling as a Simple Habit

    Microsoft Academic Search

    Michelle R. Byrd; David F. Richards; Gayleen Hove; Patrick C. Friman

    2002-01-01

    The authors evaluated the effects of response prevention, a treatment previously shown to be effective for routine thumb sucking and suggested to be effective for early onset trichotillomania, applied to hair pulling in a 2-year-old. Response prevention was used alone in two settings (bedtime and naptime) and combined with a brief time out in another (daytime). The authors also used

  9. Newer approaches to the diagnosis of early onset neonatal sepsis

    Microsoft Academic Search

    U K Mishra; S E Jacobs; L W Doyle; S M Garland

    2006-01-01

    Accurate and timely diagnosis of early onset neonatal sepsis remains challenging to the clinician and the laboratory. A test with a rapid turnaround time with 100% sensitivity, rather than high specificity, which allows accurate diagnosis and appropriate antimicrobial treatment or which allows antibiotics to be safely withheld in non-infected infants, is desirable. Many potential markers (acute phase reactants, cell surface

  10. Early onset Parkinson's disease. Part 1: The patient's story.

    PubMed Central

    Hayes, L.

    1994-01-01

    Tremors, soreness, and reduced motor control led a 35-year-old woman to her family doctor. The unwelcomed diagnosis was early onset Parkinson's disease. Meeting a family physician with whom she can jointly manage the disease has given this patient courage to face the future. Images p507-a PMID:8199507

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

    PubMed Central

    Ashtari, Fereshteh; Shaygannejad, Vahid; Farajzadegan, Ziba; Amin, Ali

    2010-01-01

    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. PMID:21526065

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

    PubMed

    Hrdlicka, Michal; Dudova, Iva

    2015-01-01

    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. PMID:25897226

  13. Early microbial succession in re-developing dental biofilms in periodontal health and disease

    PubMed Central

    TELES, F.R.; TELES, R.P.; UZEL, N.G.; SONG, X.Q.; TORRESYAP, G.; SOCRANSKY, S.S.; HAFFAJEE, A.D.

    2011-01-01

    Objective To determine the order of bacterial species succession in re-developing supra and subgingival biofilms. Methods Supra and subgingival plaque samples were taken separately from 28 teeth in 38 healthy and 17 periodontitis subjects immediately after professional cleaning. Samples were taken again from 7 teeth in randomly selected quadrants after 1, 2, 4 and 7 days of no oral hygiene and analyzed using checkerboard DNA-DNA hybridization. % DNA probe counts were averaged within subjects at each time point. Ecological succession was determined using a modified moving window analysis. Results Succession in supragingival biofilms from periodontitis and health was similar. At 1 day, Streptococcus mitis and Neisseria mucosa showed increased proportions, followed by Capnocytophaga gingivalis, Eikenella corrodens, Veillonella parvula and Streptococcus oralis at 1–4 days. At 4–7 days, Campylobacter rectus, Campylobacter showae, Prevotella melaninogenica and Prevotella nigrescens became elevated. Subgingival plaque redevelopment was slower and very different from supragingival. Increased proportions were first observed for S. mitis, followed by V. parvula and C. gingivalis and, at 7 days by Capnocytophaga sputigena and P. nigrescens. No significant increase in proportions of periodontal pathogens was observed in any of the clinical groups or locations. Conclusions There is a defined order in bacterial species succession in early supra and subgingival biofilm re-development after professional cleaning. PMID:21895662

  14. Early-onset dementias: diagnostic and etiological considerations

    PubMed Central

    2013-01-01

    This paper summarizes the body of literature about early-onset dementia (EOD) that led to recommendations from the Fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia. A broader differential diagnosis is required for EOD compared with late-onset dementia. Delays in diagnosis are common, and the social impact of EOD requires special care teams. The etiologies underlying EOD syndromes should take into account family history and comorbid diseases, such as cerebrovascular risk factors, that may influence the clinical presentation and age at onset. For example, although many EODs are more likely to have Mendelian genetic and/or metabolic causes, the presence of comorbidities may drive the individual at risk for late-onset dementia to manifest the symptoms at an earlier age, which contributes further to the observed heterogeneity and may confound diagnostic investigation. A personalized medicine approach to diagnosis should therefore be considered depending on the age at onset, clinical presentation, and comorbidities. Genetic counseling and testing as well as specialized biochemical screening are often required, especially in those under the age of 40 and in those with a family history of autosomal dominant or recessive disease. Novel treatments in the drug development pipeline for EOD, such as genetic forms of Alzheimer's disease, should target the specific pathogenic cascade implicated by the mutation or biochemical defect. PMID:24565469

  15. Treatment of early onset hair pulling as a simple habit.

    PubMed

    Byrd, Michelle R; Richards, David F; Hove, Gayleen; Friman, Patrick C

    2002-07-01

    The authors evaluated the effects of response prevention, a treatment previously shown to be effective for routine thumb sucking and suggested to be effective for early onset trichotillomania, applied to hair pulling in a 2-year-old. Response prevention was used alone in two settings (bedtime and naptime) and combined with a brief time out in another (daytime). The authors also used a novel assessment, weight of hairs pulled, and the results indicated complete cessation of hair pulling. Corresponding photographic evidence indicated complete regrowth of hair lost to pulling. These results add to a growing literature suggesting early onset hair pulling may be more appropriately classified as a benign habit than as trichotillomania. PMID:12080908

  16. Preimplantation genetic diagnosis for early-onset torsion dystonia

    Microsoft Academic Search

    S Rechitsky; O Verlinsky; A Kuliev; S Ozen; K Laziuk; R Beck; N Gleicher; Y Verlinsky

    2004-01-01

    Early-onset primary torsion dystonia (DYT1) is the most severe and common form of hereditary movement disorders, characterized by sustained twisting contractures that begin in childhood, which is caused in majority of cases by a 3-bp deletion of the DYT1 gene on chromosome 9q34 at the heterozygote state. As there is no effective treatment of this disease, preimplantation genetic diagnosis (PGD)

  17. Early onset neonatal sepsis: diagnostic dilemmas and practical management.

    PubMed

    Bedford Russell, A R; Kumar, R

    2015-07-01

    Early onset neonatal sepsis is persistently associated with poor outcomes, and incites clinical practice based on the fear of missing a treatable infection in a timely fashion. Unnecessary exposure to antibiotics is also hazardous. Diagnostic dilemmas are discussed in this review, and suggestions offered for practical management while awaiting a more rapidly available 'gold standard' test; in an ideal world, this test would be 100% sensitive and 100% specific for the presence of organisms. PMID:25425652

  18. Deferred and immediate imitation in regressive and early onset autism

    PubMed Central

    Rogers, Sally J.; Young, Gregory S.; Cook, Ian; Giolzetti, Angelo; Ozonoff, Sally

    2010-01-01

    Deferred imitation has long held a privileged position in early cognitive development, considered an early marker of representational thought with links to language development and symbolic processes. Children with autism have difficulties with several abilities generally thought to be related to deferred imitation: immediate imitation, language, and symbolic play. However, few studies have examined deferred imitation in early autism. The present study examined both deferred, spontaneous imitation and immediate, elicited imitation on a set of carefully matched tasks in 36 young children with autism: 16 with early onset autism, 20 with regressive autism and two contrast groups, younger typically developing children (n = 20) and age matched children with significant developmental delays (n = 21). Analyses of co-variance controlling for differences in verbal mental age revealed significant main effects for task, but no main effect of group and no interaction of task by group. Deferred imitation scores were lower than immediate imitation scores for all groups. Imitation performance was related to overall intellectual functioning for all groups, and there were moderate and significant relations between imitation in the immediate elicited condition and in the spontaneous deferred condition for all groups. Finally, there were no differences between onset subgroups in imitation scores, suggesting that the two share a similar phenotype involving both types of imitation. PMID:18221343

  19. Early Infantile Onset ‘‘Congenital’’ Rett Syndrome Variants: Swedish Experience Through Four Decades and Mutation Analysis

    Microsoft Academic Search

    Saideh Rajaei; Anna Erlandson; Marten Kyllerman; Margareta Albage; Isa Lundstrom; Ewa-Lotta Karrstedt; Bengt Hagberg

    2011-01-01

    The early infantile onset ‘‘congenital’’ variant of Rett syndrome presents with deviations of behavior from very early infancy. Here, we report on a clinical-genetic study in a collected series of 14 Swedish girls with early infantile onset Rett syndrome phenotype. The clinical diagnosis was based on symptom onset before the age of 6 months and the patients fulfilled 3 or

  20. Biometry of the crystalline lens in early-onset diabetes.

    PubMed Central

    Sparrow, J M; Bron, A J; Brown, N A; Neil, H A

    1990-01-01

    Lenticular biometry on non-cataractous lenses has been studied by means of Scheimpflug photography and digital image analysis in 153 patients with early-onset insulin-dependent diabetes and 153 non-diabetic controls. Anteroposterior axial lens thickness, cortical thickness, nuclear thickness, anterior and posterior lenticular curvatures, and anterior chamber depth were assessed. Highly significant differences between the lenses of the diabetic subjects and non-diabetic controls were found. After the effect of age had been accounted for within the diabetic subgroup, diabetic duration was found to be a highly significant determinant of lens dimensions, such that age-related dimensional changes for various biometric parameters were accelerated by between 52% and 121% after the onset of diabetes. Because the diabetic duration of the early-onset diabetic subjects studied in this work was accurately known, this report is the first in which a precise assessment of the effect of 'true' diabetic duration on lens biometry has been possible. PMID:2223701

  1. Susceptibility genetic variants associated with early-onset colorectal cancer.

    PubMed

    Giráldez, María Dolores; López-Dóriga, Adriana; Bujanda, Luis; Abulí, Anna; Bessa, Xavier; Fernández-Rozadilla, Ceres; Muñoz, Jenifer; Cuatrecasas, Miriam; Jover, Rodrigo; Xicola, Rosa M; Llor, Xavier; Piqué, Josep M; Carracedo, Angel; Ruiz-Ponte, Clara; Cosme, Angel; Enríquez-Navascués, José María; Moreno, Victor; Andreu, Montserrat; Castells, Antoni; Balaguer, Francesc; Castellví-Bel, Sergi

    2012-03-01

    Colorectal cancer (CRC) is the second most common cancer in Western countries. Hereditary forms only correspond to 5% of CRC burden. Recently, genome-wide association studies have identified common low-penetrant CRC genetic susceptibility loci. Early-onset CRC (CRC<50 years old) is especially suggestive of hereditary predisposition although 85-90% of heritability still remains unidentified. CRC<50 patients (n = 191) were compared with a late-onset CRC group (CRC>65 years old) (n = 1264). CRC susceptibility variants at 8q23.3 (rs16892766), 8q24.21 (rs6983267), 10p14 (rs10795668), 11q23.1 (rs3802842), 15q13.3 (rs4779584), 18q21 (rs4939827), 14q22.2 (rs4444235), 16q22.1 (rs9929218), 19q13.1 (rs10411210) and 20p12.3 (rs961253) were genotyped in all DNA samples. A genotype-phenotype correlation with clinical and pathological characteristics in both groups was performed. Risk allele carriers for rs3802842 [Odds ratio (OR) = 1.5, 95% confidence interval (CI) 1.1-2.05, P = 0.0096, dominant model) and rs4779584 (OR = 1.39, 95% CI 1.02-1.9, P = 0.0396, dominant model) were more frequent in the CRC<50 group, whereas homozygotes for rs10795668 risk allele were also more frequent in the early-onset CRC (P = 0.02, codominant model). Regarding early-onset cases, 14q22 (rs4444235), 11q23 (rs3802842) and 20p12 (rs961253) variants were more associated with family history of CRC or tumors of the Lynch syndrome spectrum excluding CRC. In our entire cohort, sum of risk alleles was significantly higher in patients with a CRC family history (OR = 1.40, 95% CI 1.06-1.85, P = 0.01). In conclusion, variants at 10p14 (rs10795668), 11q23.1 (rs3802842) and 15q13.3 (rs4779584) may have a predominant role in predisposition to early-onset CRC. Association of CRC susceptibility variants with some patient's familiar and personal features could be relevant for screening and surveillance strategies in this high-risk group and it should be explored in further studies. PMID:22235025

  2. Childhood Risk Factors for Early-Onset Drinking*

    PubMed Central

    Donovan, John E.; Molina, Brooke S. G.

    2011-01-01

    Objective: There is relatively little research on the childhood antecedent predictors of early-onset alcohol use. This study examined an array of psychosocial variables assessed at age 10 and reflecting Problem Behavior Theory as potential antecedent risk factors for the initiation of alcohol use at age 14 or younger. Method: A sample of 452 children (238 girls) ages 8 or 10 and their families was drawn from Allegheny County, PA, using targeted-age directory sampling and random-digit dialing procedures. Children and parents were interviewed using computer-assisted interviews. Logistic regression analyses were used to examine the age-10 univariate and multivariate predictors of the initiation of alcohol use by age 14 or younger. Results: Twenty-five percent of the sample reported having more than a sip or a taste of alcohol in their life by age 14. Sex, race, and age cohort did not relate to early drinking status. Children with two parents were less likely to initiate drinking early. Early initiation of drinking related significantly to an array of antecedent risk factors (personality, social environment, and behavioral) assessed at age 10 that reflect psychosocial proneness for problem behavior. In the multivariate model, the variables most predictive of early-onset drinking were having a single parent, sipping or tasting alcohol by age 10, having parents who also started drinking at an early age, and parental drinking frequency. Conclusions: Initiation of alcohol use by age 14 reflects childhood psychosocial proneness to engage in problem behavior as measured by Problem Behavior Theory and having a family environment conducive to alcohol use. PMID:21906502

  3. Auditory perceptual consolidation in early-onset blindness.

    PubMed

    Stevens, Alexander A; Weaver, Kurt

    2005-01-01

    Early-onset blindness (EB) produces measurable advantages in auditory perception, attention, memory and language. Neville and Bavelier [Neville, H. J., & Bavelier, D. (2001) Variability of developmental plasticity. In J. L. McClelland, R. S. Siegler (Eds.) Mechanisms of cognitive development: Behavioral andellon symposia on cognition (pp. 271-301)] hypothesized that faster temporal processing underlies many auditory compensatory effects in the blind. We tested this hypothesis by comparing early-onset blind individuals and sighted counterparts (SC) by assessing their rates of perceptual consolidation, the accurate perceptual representation of auditory stimuli. Firstly, we first tested both groups on a temporal-order judgment task (TOJ). EB subjects had significantly lower TOJ thresholds than the SC subjects. Secondly, we assessed perceptual consolidation speed using auditory backward masking tasks, taking into account individual TOJ thresholds. Discrimination performance was unaffected at all mask delays in the EB group while the SC subjects needed a mask delay of 160 ms to perform comparably. A backward masking task using single tone stimuli found no differences between the EB and SC groups any mask delay. A simultaneous masking task demonstrated that the mask effectively impaired discrimination in EB subjects at sensory stages. These results suggest that advantages in perceptual consolidation may reflect a mechanism responsible for the short response times and better performance reported in early blind individuals across a number of complex auditory tasks. PMID:15869766

  4. Hypergonadotropic Hypogonadism, Progressive Early-Onset Spinocerebellar Ataxia, and Late-Onset Sensorineural Hearing Loss: Case Report and Literature Review

    PubMed Central

    Sarikaya, E; Ensert, CG; Gulerman, HC

    2011-01-01

    The association of ataxia, hypergonadotropic hypogonadism and hearing loss is extremely rare. Considerable heterogeneity exists in the literature of the neurological manifestations, age of onset, clinical severity and associated abnormalities. We describe a 24-year-old woman with secondary hypergonadotropic amenorrhea, early-onset progressive spinocerebellar ataxia (SCA), late-onset sensorineural hearing loss and normal intelligence and compare it with reported cases. PMID:24052715

  5. Early onset cardiomyopathy in females with Danon disease.

    PubMed

    Hedberg Oldfors, Carola; Máthé, Gyöngyvér; Thomson, Kate; Tulinius, Mar; Karason, Kristjan; Östman-Smith, Ingegerd; Oldfors, Anders

    2015-06-01

    Danon disease is caused by mutations in the lysosome-associated membrane protein-2 gene, LAMP2, located on the X chromosome. Female carriers with LAMP2 mutations most often present with late onset cardiomyopathy and slow disease progress; however, there are unusual cases that emerge early and show a more severe disease course. We investigated the explanted heart and skeletal muscle biopsies in two girls, aged ten and thirteen years, who underwent cardiac transplantation because of hypertrophic cardiomyopathy secondary to LAMP2 mutations and a 41-year old female with late-onset familial LAMP2 cardiomyopathy with more typical clinical phenotype. The two girls in contrast had clinical features that mimicked severe primary hypertrophic cardiomyopathy caused by mutations in genes encoding sarcomeric proteins. Immunohistochemistry in cardiac muscles showed a remarkable pattern with lack of LAMP2 protein in large regions including thousands of cardiomyocytes that also showed myocyte hypertrophy, lysosomal enlargement and disarray. In other equally large regions there were preserved LAMP2 expression and nearly normal histology. The skeletal muscle biopsy revealed no pathological changes. An uneven distribution of LAMP2 protein may cause deleterious effects depending on which regions of the myocardium are lacking LAMP2 protein in spite of an overall moderate reduction of LAMP2 protein. This may be a more common mechanism behind early aggressive disease in females than an overall skewed X-chromosome inactivation in the tissue. PMID:25900304

  6. Preimplantation genetic diagnosis for early-onset torsion dystonia.

    PubMed

    Rechitsky, S; Verlinsky, O; Kuliev, A; Ozen, S; Laziuk, K; Beck, R; Gleicher, N; Verlinsky, Y

    2004-02-01

    Early-onset primary torsion dystonia (DYT1) is the most severe and common form of hereditary movement disorders, characterized by sustained twisting contractures that begin in childhood, which is caused in majority of cases by a 3-bp deletion of the DYT1 gene on chromosome 9q34 at the heterozygote state. As there is no effective treatment of this disease, preimplantation genetic diagnosis (PGD) may be a useful option for at-risk couples to establish an DYT1 mutation-free pregnancy. PGD was performed for two obligate carriers of the DYT1 3-bp deletion, using blastomere testing to preselect the mutation-free embryos, based on mutation analysis with simultaneous testing of the three closely linked markers, D9S62, D9S63 and ASS. Of 19 tested blastomeres in three cycles, 17 had conclusive information about the mutation and linked markers, of which eight were predicted to be free of 3-bp deletion. Six of these embryos were transferred back to patients, two in each cycle, yielding singleton DYT1 3-bp deletion-free clinical pregnancies in two. One of these pregnancies was terminated due to severe anencephaly and the other resulted in birth of a mutation-free child. This is the first PGD for primary torsion dystonia, providing an alternative for those at-risk couples who cannot accept prenatal diagnosis and termination of pregnancy as an option for avoiding early onset torsion dystonia. PMID:14989804

  7. Neural Abnormalities in Early-Onset and Adolescence-Onset Conduct Disorder

    PubMed Central

    Passamonti, Luca; Fairchild, Graeme; Goodyer, Ian M.; Hurford, Georgina; Hagan, Cindy C.; Rowe, James B.; Calder, Andrew J.

    2013-01-01

    Context Conduct disorder (CD) is characterized by severe antisocial behavior that emerges in childhood (early- onset CD [EO-CD]) or adolescence (adolescence-onset CD [AO-CD]). Early-onset CD is proposed to have a neurodevelopmental basis, whereas AO-CD is thought to emerge owing to social mimicry of deviant peers. However, this developmental taxonomic theory is debated after reports of neuropsychological impairments in both CD subtypes. A critical, although unaddressed, issue is whether these subtypes present similar or distinct neurophysiological profiles. Hence, we investigated neurophysiological responses to emotional and neutral faces in regions associated with antisocial behavior (ie, the amygdala, ventromedial prefrontal cortex, insula, and orbitofrontal cortex) in individuals with EO-CD and AO-CD and in healthy control subjects. Objective To investigate whether EO-CD and AO-CD subjects show neurophysiological abnormalities. Design Case-control study. Setting Government research institute, university department. Participants Seventy-five male adolescents and young adults aged 16 to 21 years, including 27 with EO-CD, 25 with AO-CD, and 23 healthy controls. Main Outcome Measure Neural activations measured by functional magnetic resonance imaging while participants viewed angry, sad, and neutral faces. Results Comparing angry vs neutral faces, participants with both CD subtypes displayed reduced responses in regions associated with antisocial behavior compared with controls; differences between the CD subtypes were not significant. Comparing each expression with fixation baseline revealed an abnormal (increased) amygdala response to neutral but not angry faces in both groups of CD relative to controls. For sad vs neutral faces, reduced amygdala activation was observed in EO-CD relative to AO-CD and control participants. Comparing each expression with fixation revealed hypoactive amygdala responses to sadness in individuals with EO-CD relative to AO-CD participants and controls. These findings were not accounted for by attention-deficit/hyperactivity disorder symptoms. Conclusions Neurophysiological abnormalities are observed in both CD subtypes, contrary to the developmental taxonomic theory of CD. Additional amygdala hypofunction in relation to sad expressions might indicate why EO-CD is more severe and persistent than AO-CD. PMID:20603454

  8. Cognitive Function in Early Onset Schizophrenia: A Selective Review

    PubMed Central

    Frangou, Sophia

    2009-01-01

    Schizophrenia is widely regarded as the clinical outcome of aberrant neurodevelopment caused by a combination of genetic and non-genetic factors. Early Onset Schizophrenia (EOS) manifests in childhood or adolescence and represents a more severe variant of the Adult Onset form of the disorder (AOS). EOS offers a unique opportunity of exploring the impact of disease related mechanisms on the developmental trajectory of cognitive function. The present review focused on the domains of general intellectual ability (IQ), attention, executive function and memory. Significant methodological variability was noted across the different studies that examined these aspects of cognition in EOS patients. Despite this, a consistent pattern emergent from the data suggesting that (a) EOS patients compared to healthy children and adolescents show impairments of medium to large effect size in IQ, attention, memory and executive function (b) despite increased clinical severity, the cognitive profile of EOS patients is comparable to that of AOS patients (c) healthy adolescents show age-related improvement in their ability to perform tests of attention, memory and executive function; this is not present in EOS patients thus resulting in increased age-related deviance in patients’ performance. This apparent decline is mostly attributable to patients’ failure to acquire new information and to use more sophisticated cognitive strategies. PMID:20140271

  9. Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS): Rationale, Design, and Methods

    ERIC Educational Resources Information Center

    McClellan, Jon; Sikich, Linmarie; Findling, Robert L.; Frazier, Jean A.; Vitiello, Benedetto; Hlastala, Stefanie A.; Williams, Emily; Ambler, Denisse; Hunt-Harrison, Tyehimba; Maloney, Ann E.; Ritz, Louise; Anderson, Robert; Hamer, Robert M.; Lieberman, Jeffrey A.

    2007-01-01

    Objective: The Treatment of Early Onset Schizophrenia Spectrum Disorders Study is a publicly funded clinical trial designed to compare the therapeutic benefits, safety, and tolerability of risperidone, olanzapine, and molindone in youths with early-onset schizophrenia spectrum disorders. The rationale, design, and methods of the Treatment of Early

  10. Role of the NK Cell-Activating Receptor CRACC in Periodontitis

    PubMed Central

    Krämer, Benjamin; Kebschull, Moritz; Nowak, Michael; Demmer, Ryan T.; Haupt, Manuela; Körner, Christian; Perner, Sven; Jepsen, Søren

    2013-01-01

    Periodontitis is a highly prevalent, biofilm-mediated chronic inflammatory disease that results in the loss of the tooth-supporting tissues. It features two major clinical entities: chronic periodontitis, which is more common, and aggressive periodontitis, which usually has an early onset and a rapid progression. Natural killer (NK) cells are a distinct subgroup of lymphocytes that play a major role in the ability of the innate immune system to steer immune responses. NK cells are abundant in periodontitis lesions, and NK cell activation has been causally linked to periodontal tissue destruction. However, the exact mechanisms of their activation and their role in the pathophysiology of periodontitis are elusive. Here, we show that the predominant NK cell-activating molecule in periodontitis is CD2-like receptor activating cytotoxic cells (CRACC). We show that CRACC induction was significantly more pronounced in aggressive than chronic periodontitis and correlated positively with periodontal disease severity, subgingival levels of specific periodontal pathogens, and NK cell activation in vivo. We delineate how Aggregatibacter actinomycetemcomitans, an oral pathogen that is causally associated with aggressive periodontitis, indirectly induces CRACC on NK cells via activation of dendritic cells and subsequent interleukin 12 (IL-12) signaling. In contrast, we demonstrate that fimbriae from Porphyromonas gingivalis, a principal pathogen in chronic periodontitis, actively attenuate CRACC induction on NK cells. Our data suggest an involvement of CRACC-mediated NK cell activation in periodontal tissue destruction and point to a plausible distinction in the pathobiology of aggressive and chronic periodontitis that may help explain the accelerated tissue destruction in aggressive periodontitis. PMID:23250953

  11. Role of the NK cell-activating receptor CRACC in periodontitis.

    PubMed

    Krämer, Benjamin; Kebschull, Moritz; Nowak, Michael; Demmer, Ryan T; Haupt, Manuela; Körner, Christian; Perner, Sven; Jepsen, Søren; Nattermann, Jacob; Papapanou, Panos N

    2013-03-01

    Periodontitis is a highly prevalent, biofilm-mediated chronic inflammatory disease that results in the loss of the tooth-supporting tissues. It features two major clinical entities: chronic periodontitis, which is more common, and aggressive periodontitis, which usually has an early onset and a rapid progression. Natural killer (NK) cells are a distinct subgroup of lymphocytes that play a major role in the ability of the innate immune system to steer immune responses. NK cells are abundant in periodontitis lesions, and NK cell activation has been causally linked to periodontal tissue destruction. However, the exact mechanisms of their activation and their role in the pathophysiology of periodontitis are elusive. Here, we show that the predominant NK cell-activating molecule in periodontitis is CD2-like receptor activating cytotoxic cells (CRACC). We show that CRACC induction was significantly more pronounced in aggressive than chronic periodontitis and correlated positively with periodontal disease severity, subgingival levels of specific periodontal pathogens, and NK cell activation in vivo. We delineate how Aggregatibacter actinomycetemcomitans, an oral pathogen that is causally associated with aggressive periodontitis, indirectly induces CRACC on NK cells via activation of dendritic cells and subsequent interleukin 12 (IL-12) signaling. In contrast, we demonstrate that fimbriae from Porphyromonas gingivalis, a principal pathogen in chronic periodontitis, actively attenuate CRACC induction on NK cells. Our data suggest an involvement of CRACC-mediated NK cell activation in periodontal tissue destruction and point to a plausible distinction in the pathobiology of aggressive and chronic periodontitis that may help explain the accelerated tissue destruction in aggressive periodontitis. PMID:23250953

  12. A Longitudinal Transactional Risk Model for Early Eating Disorder Onset

    PubMed Central

    Pearson, Carolyn M.; Combs, Jessica L.; Zapolski, Tamika C. B.; Smith, Gregory T.

    2014-01-01

    The presence of binge eating behavior in early middle school predicts future diagnoses and health difficulties. The authors showed that this early binge eating behavior can, itself, be predicted by risk factors assessed in elementary school. We tested the acquired preparedness model of risk, which involves transactions among personality, psychosocial learning, and binge eating. In a sample of 1,906 children assessed in the spring of fifth grade (the last year of elementary school), the fall of sixth grade, and the spring of sixth grade, we found that fifth grade negative urgency (the personality tendency to act rashly when distressed) predicted subsequent increases in the expectancy that eating helps alleviate negative affect, which in turn predicted subsequent increases in binge eating behavior. This transactional risk process appeared to continue to occur at later time points. Negative urgency in the fall of sixth grade was predicted by fifth grade pubertal onset, binge eating behavior, and expectancies. It, in turn, predicted increases in high-risk eating expectancies by the spring of sixth grade, and thus heightened risk. PMID:22428790

  13. Prediction of Early-Onset Esotropia From Components of the Infantile Squint Syndrome

    Microsoft Academic Search

    Clifton M. Schor; Robert E. Fusaro; Nance Wilson; Suzanne P. McKee

    Purpose. To examine the association between components of the infantile squint syndrome (ISS) and age of onset of esotropia among subjects in the Cooperative Amblyopia Classification Study (CACS). Methods. Fifty subjects were classified retrospectively as having early-onset esotropia (EOE) and 150 subjects were classified as having late-onset esotropia (LOE), depending on whether symptoms of (or treatment for) strabismus occurred before

  14. Cardiovascular disease risk factors after early-onset preeclampsia, late-onset preeclampsia, and pregnancy-induced hypertension.

    PubMed

    Veerbeek, Jan H W; Hermes, Wietske; Breimer, Anath Y; van Rijn, Bas B; Koenen, Steven V; Mol, Ben W; Franx, Arie; de Groot, Christianne J M; Koster, Maria P H

    2015-03-01

    Observational studies have shown an increased lifetime risk of cardiovascular disease (CVD) in women who experienced a hypertensive disorder in pregnancy. This risk is related to the severity of the pregnancy-related hypertensive disease and gestational age at onset. However, it has not been investigated whether these differences in CVD risk factors are already present at postpartum cardiovascular screening. We evaluated postpartum differences in CVD risk factors in 3 subgroups of patients with a history of hypertensive pregnancy. We compared the prevalence of common CVD risk factors postpartum among 448 women with previous early-onset preeclampsia, 76 women with previous late-onset preeclampsia, and 224 women with previous pregnancy-induced hypertension. Women with previous early-onset preeclampsia were compared with women with late-onset preeclampsia and pregnancy-induced hypertension and had significantly higher fasting blood glucose (5.29 versus 4.80 and 4.83 mmol/L), insulin (9.12 versus 6.31 and 6.7 uIU/L), triglycerides (1.32 versus 1.02 and 0.97 mmol/L), and total cholesterol (5.14 versus 4.73 and 4.73 mmol/L). Almost half of the early-onset preeclampsia women had developed hypertension, as opposed to 39% and 25% of women in the pregnancy-induced hypertension and late-onset preeclampsia groups, respectively. Our data show differences in the prevalence of common modifiable CVD risk factors postpartum and suggest that prevention strategies should be stratified according to severity and gestational age of onset for the hypertensive disorders of pregnancy. PMID:25561694

  15. Serum amyloid A: an early and accurate marker of neonatal early-onset sepsis

    Microsoft Academic Search

    S Arnon; I Litmanovitz; R H Regev; S Bauer; R Shainkin-Kestenbaum; T Dolfin

    2007-01-01

    Objectives:To evaluate the accuracy of serum amyloid A (SAA), an acute phase protein in the detection of neonatal early-onset sepsis, by means of a fast automated SAA kit.Study Design:Full-term infants <72 h of age, who had risk factors and\\/or were suspected of having sepsis, were eligible for study. The levels of SAA were taken at 0, 24 and 48 h

  16. The Maudsley early onset schizophrenia study. Predictors of psychosocial outcome at 4-year follow-up

    Microsoft Academic Search

    Nora S. Vyas; Michael Hadjulis; Sophia Frangou

    2007-01-01

    Objective To examine the contribution of premorbid function, duration of untreated psychosis (DUP), age of onset, severity of symptoms at presentation, and number of subsequent hospitalisations to the outcome of early onset schizophrenia (EOS; onset before 17th birthday). Method Twenty-three EOS patients (mean age at onset 15.16 ± 1.39 years) were re-assessed after a mean interval of 4 ± 1.08 years. At baseline and follow-up clinical

  17. Early onset of ghrelin production in a marsupial.

    PubMed

    Menzies, Brandon R; Shaw, Geoff; Fletcher, Terry P; Renfree, Marilyn B

    2009-02-27

    Ghrelin regulates appetite in mammals and can stimulate growth hormone (GH) release from the pituitary. In rats and humans, ghrelin cells appear in the stomach during late fetal life. Nevertheless, the role of ghrelin in early mammalian development is not well understood. Marsupials deliver highly altricial young that weigh less than 1g so they must feed and digest milk at a comparatively immature stage of development. Since they complete their growth and differentiation while in the pouch, they are accessible models in which to determine the time course of ghrelin production during development. We examined the distribution of gastric ghrelin cells, plasma ghrelin concentrations and pituitary expression of the ghrelin receptor (ghsr-1alpha) and GH in the tammar wallaby, Macropus eugenii. There were ghrelin immunopositive cells in the developing mesenchyme of the stomach from day 10 post partum (pp) to day 150pp. Subsequently ghrelin protein in the fore-stomach declined and was absent by day 250pp but remained in the gastric cells of the hind-stomach. Ghrelin was detected in the developing pancreas from day 10pp but was absent by day 150pp and in the adult. Pituitary ghsr-1alpha expression and plasma concentrations of ghrelin increased significantly up to day 70-120pp while GH expression was also elevated, declining with GH to reach adult levels by day 180pp. These results demonstrate an early onset of gastric ghrelin expression in the tammar in concert with a functional stomach at a relatively earlier stage than that of developmentally more mature eutherian young. PMID:19026714

  18. Facial emotion identification in early-onset psychosis.

    PubMed

    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. PMID:25464918

  19. Child and Adolescent (Early Onset) Schizophrenia: A Review in Light of DSM-III-R.

    ERIC Educational Resources Information Center

    Werry, John S.

    1992-01-01

    This review of studies of early onset schizophrenia examines the nosological similarity between adult and early onset schizophrenia, differential diagnosis, treatment, and the extent to which children and adolescents diagnosed as having schizophrenia using adult criteria have the characteristic adult correlates. The paper discusses gender…

  20. Internalizing and Externalizing Behaviors as Predictors of Sexual Onset in Early Adolescence

    ERIC Educational Resources Information Center

    Boislard, Marie-Aude P.; Dussault, Frédéric; Brendgen, Mara; Vitaro, Frank

    2013-01-01

    This study had three goals: (a) assessing the predictive association of externalizing and internalizing behaviors during childhood with sexual onset during early adolescence; (b) examining the interactive link of externalizing and internalizing behaviors with early sexual onset; and (c) investigating the moderating effect of gender in this…

  1. Children with Very Early Onset Obsessive-Compulsive Disorder: Clinical Features and Treatment Outcome

    ERIC Educational Resources Information Center

    Nakatani, Eriko; Krebs, Georgina; Micali, Nadia; Turner, Cynthia; Heyman, Isobel; Mataix-Cols, David

    2011-01-01

    Background: There is emerging evidence that early onset obsessive-compulsive disorder (OCD) may be a phenomenologically distinct subtype of the disorder. Previous research has shown that individuals who report an early onset display greater severity and persistence of symptoms, and they may be less responsive to treatment. To date, this question…

  2. Referral and Experience with Genetic Testing Among Women with Early Onset Breast Cancer

    Microsoft Academic Search

    Karen L. Brown; Robin Hutchison; Randi E. Zinberg; Margaret M. McGovern

    2005-01-01

    The purpose of this study was to determine whether physicians refer women with early onset breast cancer for genetic testing for BRCA1 and BRCA2, and how women respond to being offered testing and use the re- sults. A web-based survey was distributed to 1221 women with early onset breast cancer. The survey included 158 questions divided into the following sections:

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

    ERIC Educational Resources Information Center

    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…

  4. A Functional Mutation in the Terminal Exon of Elastin in Severe, Early-Onset Chronic Obstructive

    E-print Network

    Mecham, Robert

    A Functional Mutation in the Terminal Exon of Elastin in Severe, Early-Onset Chronic Obstructive of glycine 773 to aspartate (G773D) in a pedigree with severe early-onset chronic obstructive pulmonary to the pathogenesis of COPD. Keywords: chronic obstructive pulmonary disease; elastin; extracellular matrix; genetics

  5. Early onset severe and late-onset mild Charcot-Marie-Tooth disease with mitofusin 2 (MFN2) mutations.

    PubMed

    Chung, K W; Kim, S B; Park, K D; Choi, K G; Lee, J H; Eun, H W; Suh, J S; Hwang, J H; Kim, W K; Seo, B C; Kim, S H; Son, I H; Kim, S M; Sunwoo, I N; Choi, B O

    2006-08-01

    Mutations in the mitofusin 2 (MFN2) gene, which encodes a mitochondrial GTPase mitofusin protein, have recently been reported to cause both Charcot-Marie-Tooth 2A (CMT2A) and hereditary motor and sensory neuropathy VI (HMSN VI). It is well known that HMSN VI is an axonal CMT neuropathy with optic atrophy. However, the differences between CMT2A and HMSN VI with MFN2 mutations remained to be clarified. Therefore, we studied the phenotypic characteristics of CMT patients with MFN2 mutations. Mutations in MFN2 were screened in 62 unrelated axonal CMT neuropathy families. We calculated CMT neuropathy scores (CMTNSs) and functional disability scales (FDSs) to quantify disease severity. Twenty-one patients with the MFN2 mutations were studied by brain MRI. Ten pathogenic mutations were identified in 26 patients from 15 families (24.2%). Six of these mutations had not been reported, and de novo mutations were observed in five families (33.3%). The electrophysiological patterns of affected individuals with the MFN2 mutations were typical of axonal CMT; however, the clinical and electrophysiological characteristics were markedly different in early (<10 years) and late disease-onset (> or =10 years) groups. All patients with an early onset had severe CMTNS (> or =21) and FDS (6 or 7), whereas most patients with late onset had mild CMTNS (< or =10) and FDS (< or =3). We identified two HMSN VI families with the R364W mutation in the early onset group; however, two other families with the same mutation did not have optic atrophy. In addition, two early onset families with R94W mutations, previously reported for HMSN VI, did not have visual impairment. Interestingly, eight patients had periventricular and subcortical hyperintense lesions by brain MRI. In the late-onset group, three patients had sensorineural hearing loss and two had bilateral extensor plantar responses. We found that MFN2 mutations are the major cause of axonal CMT neuropathy, and that they are associated with variable CNS involvements. Phenotypes were significantly different in the early and late disease-onset groups. Our findings suggest that HMSN VI might be a variant of the early onset severe CMT2A phenotype. PMID:16835246

  6. Distributional Cues and the Onset Bias in Early Word Segmentation

    ERIC Educational Resources Information Center

    Babineau, Mireille; Shi, Rushen

    2014-01-01

    In previous infant studies on statistics-based word segmentation, the unit of statistical computation was always aligned with the syllabic edge, which had a consonant onset. The current study addressed whether the learning system imposes a constraint that favors word forms beginning with a consonant onset over those beginning with an onsetless…

  7. Immediate, Early, and Conventional Implant Placement in a Patient with History of Periodontitis

    PubMed Central

    Lanza, Alessandro; Scognamiglio, Fabio; Femiano, Felice; Lanza, Michele

    2015-01-01

    The aim of this paper is to describe a case of implant-prosthetic rehabilitation in a patient with periodontitis, focusing on the different timing of implant placement. After initial periodontal treatment, teeth with advanced mobility degree and severe bone resorption were extracted. At different healing time oral implants were placed in a prosthetic-guided position. After osseointegration period the implants were loaded and the results at one year of follow-up are presented. PMID:25949833

  8. Increased Genetic Vulnerability to Smoking at CHRNA5 in Early-Onset Smokers

    PubMed Central

    Hartz, Sarah M.; Short, Susan E.; Saccone, Nancy L.; Culverhouse, Robert; Chen, LiShiun; Schwantes-An, Tae-Hwi; Coon, Hilary; Han, Younghun; Stephens, Sarah H.; Sun, Juzhong; Chen, Xiangning; Ducci, Francesca; Dueker, Nicole; Franceschini, Nora; Frank, Josef; Geller, Frank; Gu?bjartsson, Daniel; Hansel, Nadia N.; Jiang, Chenhui; Keskitalo-Vuokko, Kaisu; Liu, Zhen; Lyytikäinen, Leo-Pekka; Michel, Martha; Rawal, Rajesh; Hum, Sc; Rosenberger, Albert; Scheet, Paul; Shaffer, John R.; Teumer, Alexander; Thompson, John R.; Vink, Jacqueline M.; Vogelzangs, Nicole; Wenzlaff, Angela S.; Wheeler, William; Xiao, Xiangjun; Yang, Bao-Zhu; Aggen, Steven H.; Balmforth, Anthony J.; Baumeister, Sebastian E.; Beaty, Terri; Bennett, Siiri; Bergen, Andrew W.; Boyd, Heather A.; Broms, Ulla; Campbell, Harry; Chatterjee, Nilanjan; Chen, Jingchun; Cheng, Yu-Ching; Cichon, Sven; Couper, David; Cucca, Francesco; Dick, Danielle M.; Foroud, Tatiana; Furberg, Helena; Giegling, Ina; Gu, Fangyi; Hall, Alistair S.; Hällfors, Jenni; Han, Shizhong; Hartmann, Annette M.; Hayward, Caroline; Heikkilä, Kauko; Lic, Phil; Hewitt, John K.; Hottenga, Jouke Jan; Jensen, Majken K.; Jousilahti, Pekka; Kaakinen, Marika; Kittner, Steven J.; Konte, Bettina; Korhonen, Tellervo; Landi, Maria-Teresa; Laatikainen, Tiina; Leppert, Mark; Levy, Steven M.; Mathias, Rasika A.; McNeil, Daniel W.; Medland, Sarah E.; Montgomery, Grant W.; Muley, Thomas; Murray, Tanda; Nauck, Matthias; North, Kari; Pergadia, Michele; Polasek, Ozren; Ramos, Erin M.; Ripatti, Samuli; Risch, Angela; Ruczinski, Ingo; Rudan, Igor; Salomaa, Veikko; Schlessinger, David; Styrkársdóttir, Unnur; Terracciano, Antonio; Uda, Manuela; Willemsen, Gonneke; Wu, Xifeng; Abecasis, Goncalo; Barnes, Kathleen; Bickeböller, Heike; Boerwinkle, Eric; Boomsma, Dorret I.; Caporaso, Neil; Duan, Jubao; Edenberg, Howard J.; Francks, Clyde; Gejman, Pablo V.; Gelernter, Joel; Grabe, Hans Jörgen; Hops, Hyman; Jarvelin, Marjo-Riitta; Viikari, Jorma; Kähönen, Mika; Kendler, Kenneth S.; Lehtimäki, Terho; Levinson, Douglas F.; Marazita, Mary L.; Marchini, Jonathan; Melbye, Mads; Mitchell, Braxton D.; Murray, Jeffrey C.; Nöthen, Markus M.; Penninx, Brenda W.; Raitakari, Olli; Rietschel, Marcella; Rujescu, Dan; Samani, Nilesh J.; Sanders, Alan R.; Schwartz, Ann G.; Shete, Sanjay; Shi, Jianxin; Spitz, Margaret; Stefansson, Kari; Swan, Gary E.; Thorgeirsson, Thorgeir; Völzke, Henry; Wei, Qingyi; Wichmann, H.-Erich; Amos, Christopher I.; Breslau, Naomi; Cannon, Dale S.; Ehringer, Marissa; Grucza, Richard; Hatsukami, Dorothy; Heath, Andrew; Johnson, Eric O.; Kaprio, Jaakko; Madden, Pamela; Martin, Nicholas G.; Stevens, Victoria L.; Stitzel, Jerry A.; Weiss, Robert B.; Kraft, Peter; Bierut, Laura J.

    2012-01-01

    Context Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968. Objective To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking. Data Sources Primary data. Study Selection Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy. Data Extraction Uniform statistical analysis scripts were run locally. Starting with 94 050 ever-smokers from 43 studies, we extracted the heavy smokers (CPD >20) and light smokers (CPD ?10) with age-at-onset information, reducing the sample size to 33 348. Each study was stratified into early-onset smokers (age at onset ?16 years) and late-onset smokers (age at onset >16 years), and a logistic regression of heavy vs light smoking with the rs16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum. Data Synthesis Individuals with 1 risk allele at rs16969968 who were early-onset smokers were significantly more likely to be heavy smokers in adulthood (odds ratio [OR]=1.45; 95% CI, 1.36–1.55; n=13 843) than were carriers of the risk allele who were late-onset smokers (OR = 1.27; 95% CI, 1.21–1.33, n = 19 505) (P = .01). Conclusion These results highlight an increased genetic vulnerability to smoking in early-onset smokers. PMID:22868939

  9. Dissecting Allele Architecture of Early Onset IBD Using High-Density Genotyping

    PubMed Central

    Prahalad, Sampath; Walters, Thomas; Guthery, Stephen L.; Dubinsky, Marla; Baldassano, Robert; Crandall, Wallace V.; Rosh, Joel; Markowitz, James; Stephens, Michael; Kellermayer, Richard; Pfefferkorn, Marian; Heyman, Melvin B.; LeLeiko, Neal; Mack, David; Moulton, Dedrick; Kappelman, Michael D.; Kumar, Archana; Prince, Jarod; Bose, Promita; Mondal, Kajari; Ramachandran, Dhanya; Bohnsack, John F.; Griffiths, Anne M.; Haberman, Yael; Essers, Jonah; Thompson, Susan D.; Aronow, Bruce; Keljo, David J.; Hyams, Jeffrey S.; Denson, Lee A.; Kugathasan, Subra

    2015-01-01

    Background The inflammatory bowel diseases (IBD) are common, complex disorders in which genetic and environmental factors are believed to interact leading to chronic inflammatory responses against the gut microbiota. Earlier genetic studies performed in mostly adult population of European descent identified 163 loci affecting IBD risk, but most have relatively modest effect sizes, and altogether explain only ~20% of the genetic susceptibility. Pediatric onset represents about 25% of overall incident cases in IBD, characterized by distinct disease physiology, course and risks. The goal of this study is to compare the allelic architecture of early onset IBD with adult onset in population of European descent. Methods We performed a fine mapping association study of early onset IBD using high-density Immunochip genotyping on 1008 pediatric-onset IBD cases (801 Crohn’s disease; 121 ulcerative colitis and 86 IBD undetermined) and 1633 healthy controls. Of the 158 SNP genotypes obtained (out of the 163 identified in adult onset), this study replicated 4% (5 SNPs out of 136) of the SNPs identified in the Crohn’s disease (CD) cases and 0.8% (1 SNP out of 128) in the ulcerative colitis (UC) cases. Replicated SNPs implicated the well known NOD2 and IL23R. The point estimate for the odds ratio (ORs) for NOD2 was above and outside the confidence intervals reported in adult onset. A polygenic liability score weakly predicted the age of onset for a larger collection of CD cases (p< 0.03, R2= 0.007), but not for the smaller number of UC cases. Conclusions The allelic architecture of common susceptibility variants for early onset IBD is similar to that of adult onset. This immunochip genotyping study failed to identify additional common variants that may explain the distinct phenotype that characterize early onset IBD. A comprehensive dissection of genetic loci is necessary to further characterize the genetic architecture of early onset IBD. PMID:26098103

  10. Aggressive and acute periodontal diseases.

    PubMed

    Albandar, Jasim M

    2014-06-01

    Inflammatory periodontal diseases are highly prevalent, although most of these diseases develop and progress slowly, often unnoticed by the affected individual. However, a subgroup of these diseases include aggressive and acute forms that have a relatively low prevalence but show a rapid-course, high rate of progression leading to severe destruction of the periodontal tissues, or cause systemic symptoms that often require urgent attention from healthcare providers. Aggressive periodontitis is an early-onset, destructive disease that shows a high rate of periodontal progression and distinctive clinical features. A contemporary case definition of this disease is presented. Population studies show that the disease is more prevalent in certain geographic regions and ethnic groups. Aggressive periodontitis is an infectious disease, and recent data show that in affected subjects the subgingival microbiota is composed of a mixed microbial infection, with a wide heterogeneity in the types and proportions of microorganisms recovered. Furthermore, there are significant differences in the microbiota of the disease among different geographic regions and ethnicities. There is also evidence that the Aggregatibacter actinomycetemycomitans-JP2 clone may play an important role in the development of the disease in certain populations. The host response plays an important role in the susceptibility to aggressive periodontitis, where the immune response may be complex and involve multiple mechanisms. Also, genetic factors seem to play an important role in the pathogenesis of this disease, but the mechanisms of increased susceptibility are complex and not yet fully understood. The available data suggest that aggressive periodontitis is caused by mutations either in a few major genes or in multiple small-effect genes, and there is also evidence of gene-gene and gene-environment interaction effects. Diagnostic methods for this disease, based on a specific microbiologic, immunologic or genetic profile, currently do not exist. Genetic markers have the potential to be implemented as screening tools to identify subjects at risk. This approach may significantly enhance treatment outcome through the early detection and treatment of affected subjects, as well as using future approaches based on gene therapy. At present, the treatment of this disease is directed toward elimination of the subgingival bacterial load and other local risk factors. Adjunctive use of appropriate systemic antibiotics is recommended and may contribute to a longer suppression of the microbial infection. Other aggressive forms of periodontal diseases occur in patients who are affected with certain systemic diseases, including the leukocyte adhesion deficiency syndrome, Papillon-Lefèvre syndrome, Chediak-Higashi syndrome and Down syndrome. Management of the periodontal component of these diseases is very challenging. Acute gingival and periodontal lesions include a group of disorders that range from nondestructive to destructive forms, and these lesions are usually associated with pain and are a common reason for emergency dental consultations. Some of these lesions may cause a rapid and severe destruction of the periodontal tissues and loss of teeth. Oral infections, particularly acute infections, can spread to extra-oral sites and cause serious medical complications, and even death. Hence, prompt diagnosis and treatment are paramount. PMID:24738583

  11. Risk factors and characteristics of early-onset asthma in Taiwanese children

    Microsoft Academic Search

    Pei-Hsuan Liang; Shyh-Dar Shyur; Li-Hsin Huang; Da-Chin Wen; Yi-Chi Chiang; Mao-Tsair Lin; Hwai-Chih Yang

    Background and Purpose: Early-onset asthma has been reported to be associated with a family history of allergy and exposure to environmental factors. This study was designed to evaluate the relationship between age of onset of asthma and genetic and environmental factors with asthma severity in Taiwanese children. Methods: A group of 352 children with asthma (220 males and 132 females),

  12. Early-Onset Obsessive-Compulsive Disorder: A Subgroup with a Specific Clinical and Familial Pattern?

    ERIC Educational Resources Information Center

    Chabane, Nadia; Delorme, Richard; Millet, Bruno; Mouren, Marie-Christine; Leboyer, Marion; Pauls, David

    2005-01-01

    Background: The familial nature of obsessive-compulsive disorder (OCD) has been previously demonstrated. The identification of candidate symptoms such as age at onset may help to disentangle the clinical and genetic heterogeneity of the disorder. In this study, the specificity of early-onset OCD was investigated, focusing on the effect of gender,…

  13. Global and Temporal Cortical Folding in Patients with Early-Onset Schizophrenia

    ERIC Educational Resources Information Center

    Penttila, Jani; Paillere-Martinot, Marie-Laure; Martinot, Jean-Luc; Mangin, Jean-Francois; Burke, Lisa; Corrigall, Richard; Frangou, Sophia; Cachia, Arnaud

    2008-01-01

    Disturbances in the temporal lobes and alterations in cortical folding in adult on-set schizophrenia are studied using magnetic resonance T1 images of 51 patients. The study showed that patients with early on-set schizophrenia had lower global sulcal indices in both hemispheres and the left collateral sulcus has a lower sulcal index irrespective…

  14. The impact of early-onset cannabis use on functional brain correlates of working memory

    Microsoft Academic Search

    Benjamin Becker; Daniel Wagner; Euphrosyne Gouzoulis-Mayfrank; Elmar Spuentrup; Jörg Daumann

    2010-01-01

    Cannabis is the most commonly used illicit drug. Prevalence rates are particularly high among adolescents. Neuropsychological studies have identified cannabis-associated memory deficits, particularly linked to an early onset of use. However, it remains unclear, whether the age of onset accounts for altered cortical activation patterns usually observed in cannabis users. Functional magnetic resonance imaging was used to examine cortical activation

  15. Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS): Demographic and Clinical Characteristics

    Microsoft Academic Search

    JEAN A. FRAZIER; JON McCLELLAN; ROBERT L. FINDLING; BENEDETTO VITIELLO; ROBERT ANDERSON; BENJAMIN ZABLOTSKY; EMILY WILLIAMS; NORA K. McNAMARA; JOSEPH A. JACKSON; LOUISE RITZ; STEFANIE A. HLASTALA; LESLIE PIERSON; JENNIFER A. VARLEY; MADELINE PUGLIA; ANN E. MALONEY; DENISSE AMBLER; TYEHIMBA HUNT-HARRISON; ROBERT M. HAMER; NANCY NOYES; JEFFREY A. LIEBERMAN; LINMARIE SIKICH

    2007-01-01

    Objective:We examined baseline demographic and clinical profiles of youths enrolled from 2001 to 2006 in the publicly funded multicenter, randomized controlled trial Treatment of Early-Onset Schizophrenia Spectrum Disorders.

  16. Periodontal disease, atherosclerosis, adverse pregnancy outcomes, and head-and-neck cancer.

    PubMed

    Han, Y W; Houcken, W; Loos, B G; Schenkein, H A; Tezal, M

    2014-05-01

    Interrelationships between periodontal infection and systemic conditions such as cardiovascular disease, adverse pregnancy outcomes, and head-and-neck cancer have become increasingly appreciated in recent years. Periodontitis is associated with cardiovascular disease (CVD) and, experimentally, with measures of atherosclerosis and endothelial dysfunction. Periodontal therapy may reduce atherosclerotic changes and improve endothelial function. Preliminary findings suggest a role for the genetic locus ANRIL in the pathobiology of both CVD and periodontitis. Periodontal pathogens induce anticardiolipin in periodontitis patients by molecular mimicry of the serum protein ?-2 glycoprotein I. These antibodies have biological and pathological activities consistent with those reported for other infection-induced antiphospholipid antibodies. Anticardiolipin may explain some of the observed associations between periodontitis and systemic conditions such as CVD and adverse pregnancy outcomes. The oral commensal Fusobacterium nucleatum (Fn) becomes pathogenic on migration to extra-oral sites. Fn infection of the fetal-placental unit has been linked to pregnancy complications, including preterm birth, stillbirth, and early-onset neonatal sepsis. Reagents aimed at inhibiting or resolving inflammatory responses may be used to treat or prevent pregnancy complications due to bacterial infection. Chronic periodontitis may be independently associated with head-and-neck squamous cell carcinoma (HNSCC) through direct toxic effects of bacteria and their products, and/or through indirect effects of inflammation. Additionally, chronic periodontitis may facilitate the acquisition and persistence of oral HPV infection, a recently emerged risk factor for HNSCC. PMID:24736704

  17. Substance abuse treatment patients with early onset cocaine use respond as well to contingency management interventions as those with later onset cocaine use.

    PubMed

    Weiss, Lindsay M; Petry, Nancy M

    2014-08-01

    Early onset drug use is associated with increased risk of developing substance use disorders, but relatively little is known about the correlates of early drug use among adults receiving treatment. A retrospective analysis of a randomized study of contingency management treatment compared cocaine-dependent patients who reported initial cocaine use at age 14 or younger (n = 41) to those who began using after age 14 (n = 387). Patients with early onset cocaine use had more legal and psychiatric problems than those who initiated cocaine use later. Patients with early-onset cocaine use also dropped out of treatment sooner and achieved less sustained abstinence than those who began using at older ages, but the interaction between age of first use and treatment condition was not significant. Early-onset cocaine use is associated with persistent psychosocial problems and an overall poor response to treatment. However, contingency management is efficacious in improving outcomes in early onset cocaine users. PMID:24865619

  18. Early Onset of Puberty: Tracking Genetic and Environmental Factors

    Microsoft Academic Search

    Anne-Simone Parent; Gregory Rasier; Arlette Gerard; Sabine Heger; Christian Roth; Claudio Mastronardi; Heike Jung; Sergio R. Ojeda; Jean-Pierre Bourguignon

    2005-01-01

    Under physiological conditions, factors affecting the genetic control of hypothalamic functions are predominant in determining the individual variations in timing of pubertal onset. In pathological conditions, however, these variations can involve different genetic susceptibility and the interaction of environmental factors. The high incidence of precocious puberty in foreign children migrating to Belgium and the detection in their plasma of a

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

    Microsoft Academic Search

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

    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

  20. Early-onset seizure variant of Rett syndrome: Definition of the clinical diagnostic criteria

    Microsoft Academic Search

    R. Artuso; M. A. Mencarelli; R. Polli; S. Sartori; F. Ariani; M. Pollazzon; A. Marozza; M. R. Cilio; N. Specchio; F. Vigevano; M. Vecchi; C. Boniver; B. Dalla Bernardina; A. Parmeggiani; S. Buoni; G. Hayek; F. Mari; A. Renieri; A. Murgia

    2010-01-01

    Background: Rett syndrome is a severe neurodevelopmental disorder affecting almost exclusively females. Among Rett clinical variants, the early-onset seizure variant describes girls with early onset epilepsy and it is caused by mutations in CDKL5. Methods: Four previously reported girls and five new cases with CDKL5 mutation, ranging from 14months to 13years, were evaluated by two clinical geneticists, classified using a

  1. Early infantile onset ''congenital'' Rett syndrome variants: Swedish experience through four decades and mutation analysis.

    PubMed

    Rajaei, Saideh; Erlandson, Anna; Kyllerman, Marten; Albage, Margareta; Lundstrom, Isa; Karrstedt, Ewa-Lotta; Hagberg, Bengt

    2011-01-01

    The early infantile onset ''congenital'' variant of Rett syndrome presents with deviations of behavior from very early infancy. Here, we report on a clinical-genetic study in a collected series of 14 Swedish girls with early infantile onset Rett syndrome phenotype. The clinical diagnosis was based on symptom onset before the age of 6 months and the patients fulfilled 3 or more Rett variant criteria and 5 or more supportive criteria. Genotype-phenotype correlation studies in the CDKL5-gene have recently shown clinical associations to early infantile onset Rett variants. Mutation analyses for both the MECP2-gene and the CDKL5-gene were, therefore, performed. Of interest, we found a large deletion covering 2 exons in MECP2, which underlines the importance of MECP2 mutation screening even for the ''atypical'' early infantile onset variants of Rett syndrome. No early infantile onset Rett syndrome patients in this study had the previously well-known hotspot mutations in the MECP2-gene. PMID:21212452

  2. Parental Alcohol Use and Brain Volumes in Early and Late-Onset Alcoholics

    PubMed Central

    Gilman, Jodi M.; Bjork, James M.; Hommer, Daniel W.

    2007-01-01

    Background Studies have shown that alcoholics have smaller brain volumes than non-alcoholic cohorts, but an effect of family history of heavy drinking on brain volume has not been demonstrated. We examined the relationship between a family history of heavy drinking and both brain shrinkage as measured by the ratio of brain volumes to intracranial volume (ICV) as well as maximal brain growth as measured by ICV in early-onset and late-onset alcoholics. Methods Using T1-weighted resonance imaging, we measured ICV, brain volume, and white and gray matter volume in adult treatment-seeking late-onset and early-onset alcoholics with either a positive or a negative family history (FH) of heavy alcohol use, and in healthy controls. We also calculated brain shrinkage using a ratio of soft tissue volumes to ICV. Results FH positive alcoholic patients had significantly smaller ICVs than FH negative patients, suggesting smaller premorbid brain growth. Brain shrinkage did not correlate with FH. Late-onset alcoholics showed a greater difference in ICV between FH positive and FH negative patients than early-onset alcoholics. Late-onset FH positive patients also had significantly lower IQ scores than late-onset FH negative patients, and IQ scores were correlated with ICV. Conclusions These data provide evidence that parental alcohol use may increase risk for alcoholism in offspring in part by a genetic and/or environmental effect that may be related to reduced brain growth. PMID:17306776

  3. Early recognition improves prognosis in elderly onset RA. .

    PubMed

    Negoescu, Andra; Ostör, Andrew J K

    2014-01-01

    Although commonly diagnosed in the third to fifth decades of life, the incidence and prevalence of RA continue to increase up to the ninth decade. Age at onset is particularly relevant as the presentation may differ in elderly onset RA (EORA) compared with young onset RA (YORA). Patients with EORA frequently report a more acute presentation, especially if positive for rheumatoid factor (RF). Fever, fatigue and weight loss appear to be more common in EORA. Although small joints are most frequently involved in the RA population overall, there is common involvement of large joints in EORA and these proximal symptoms may mimic polymyalgia rheumatica (PMR). In YORA, approximately 80% of patients are seropositive for RF however a lower frequency has been reported in EORA. Anti-CCP antibodies have been detected in over 70% of patients with RA and are highly specific for RA. The value of anti-CCP antibodies is even higher in patients with an atypical presentation (e.g. PMR-like symptoms), or those who are RF negative. X-rays of the hands and feet should always be performed in patients with a suspected inflammatory arthritis. Baseline joint erosions are present in a similar proportion in patients with YORA and EORA. In the elderly, the differential diagnosis of RA is extensive as many conditions present in a similar way e.g. PMR, osteoarthritis, polyarticular gout, pseudogout and malignancy. Anti-CCP antibodies are very useful for identifying EORA patients with a polymyalgic onset. Ultrasonography or MRI can also be helpful in differentiating PMR from EORA. PMID:24617098

  4. The effect of early onset common mental disorders on educational attainment in Australia.

    PubMed

    Leach, Liana Sarma; Butterworth, Peter

    2012-08-30

    Early onset mental disorders may lead to the early termination of education and thereby have long term adverse social and economic consequences on outcomes such as employment and financial security. This issue is important to address as governments seek to develop new ways to minimise the impacts of mental health problems and maximise workforce participation. The current investigation examines the impact of early onset affective, anxiety and substance use disorders on the early termination of secondary school education in Australia. The analyses used data from those aged between 20 and 34 in the 2007 Australian National Survey of Mental Health and Wellbeing (NSMHWB) (n=2055). The NSMHWB is a population based survey administered by the Australian Bureau of Statics and included a WMH-CIDI 3.0 assessment to determine whether respondents met diagnostic criteria for any lifetime affective, anxiety, and/or substance use disorder as well as age of onset information. The results show that early onset mental disorders are significantly associated with the termination of secondary education in Australia, particularly early onset substance use disorders such as alcohol, cannabis and stimulant use. These disorders were most likely to disrupt completion in the middle years of high school (year 10 completion), in comparison to the final year 12 milestone. Policies and interventions promoting prevention and early intervention and offering educational support for young people with psychiatric illness and substance use problems, should intervene prior to the middle years of high school to help prevent adverse social and economic consequences. PMID:22507527

  5. Family functioning and early onset of sexual intercourse in Latino adolescents.

    PubMed

    Vélez-Pastrana, Maria C; González-Rodríguez, Rafael A; Borges-Hernández, Adalisse

    2005-01-01

    The purpose of this study was to identify factors associated with early onset of sexual intercourse. Within an ecological system's conceptual framework, familial factors associated with early onset of sexual activity were identified in a sample of 425 adolescents from San Juan metro area schools. Measures included questions about sexual activity, sexual permissiveness, and such familial variables as: discipline, parental supervision, and parental support. Significant relationships were observed between early onset of sexual intercourse and parental supervision, discipline, parental support, and parents' marital status. Results suggest the key role of parents and family in prevention of HIV-risk behaviors among adolescents in terms of delaying sexual onset. Overall, the study described youths who postponed sexual activity as having greater support, supervision, and parental involvement. PMID:16468671

  6. Asthma onset prior to multiple sclerosis and the contribution of sibling exposure in early life

    E-print Network

    Cochran-Stafira, D. Liane

    Asthma onset prior to multiple sclerosis and the contribution of sibling exposure in early life A with a reduced risk of asthma and other T helper 2 (Th2)-type disorders, possibly through a beneficial effect examine the association between asthma and MS, taking into account early life sibling exposure

  7. Depression and Anxiety Symptoms: Onset, Developmental Course and Risk Factors during Early Childhood

    ERIC Educational Resources Information Center

    Cote, Sylvana M.; Boivin, Michel; Liu, Xuecheng; Nagin, Daniel S.; Zoccolillo, Mark; Tremblay, Richard E.

    2009-01-01

    Background: Depressive and anxiety disorders are among the top ten leading causes of disabilities. We know little, however, about the onset, developmental course and early risk factors for depressive and anxiety symptoms (DAS). Objective: Model the developmental trajectories of DAS during early childhood and to identify risk factors for atypically…

  8. Distinguishing the early-onset/persistent and adolescence-onset antisocial behavior types: from birth to 16 years.

    PubMed

    Aguilar, B; Sroufe, L A; Egeland, B; Carlson, E

    2000-01-01

    Moffitt's theory regarding two types of adolescent antisocial behavior was investigated using a prospective, longitudinal study of normal and abnormal development in a primarily low socioeconomic status, ethnically diverse sample. Results supported the presence of an early-onset/persistent (EOP) group and an adolescence-onset (AO) group. Groups were most reliably and significantly distinguished by indices of socioemotional history within the first 3 years, but no significant differences were found on early measures of temperament or neuropsychological functioning. EOPs scored significantly lower than other groups on measures of neuropsychological functioning only during late childhood and adolescence, suggesting that the declines in verbal functioning that have been so reliably found in this and other samples of early-starting antisocial adolescents are progressive and consequent to adverse experience. In adolescence, AOs were significantly more likely to report high levels of internalizing symptoms and life stress, suggesting that AO antisocial behavior is not a benign phenomenon. Implications of these findings for etiologic theories of adolescent antisocial behavior are discussed. PMID:10847620

  9. Early onset type 2 diabetes: risk factors, clinical impact and management

    PubMed Central

    Idris, Iskandar

    2014-01-01

    Early onset type 2 diabetes mellitus (T2DM) is increasingly prevalent with a significant impact on the individual, healthcare service delivery and planning. The individuals are likely to be obese, lead a sedentary lifestyle, have a strong family history of T2DM, be of black and minority ethnic (BME) origin and come from a less affluent socioeconomic group. They have a heightened risk of developing microvascular and macrovascular complications, often at an earlier stage and with greater frequency than seen in type 1 diabetes. As such, early and aggressive risk factor management is warranted. Early onset T2DM is complex and impacts on service delivery with a need for multidisciplinary care of complications and comorbidities’, in addition to adequate educational and psychological support. This review on the impact of early onset T2DM provides the latest insights into this emerging epidemic. PMID:25364491

  10. Early colonization of non-submerged dental implants in patients with a history of advanced aggressive periodontitis.

    PubMed

    De Boever, Annemarie L; De Boever, Jan A

    2006-02-01

    The aim of the study was to evaluate the early colonization of non-submerged implants over a 6-month period in partially edentulous patients treated for advanced aggressive periodontal disease. In 22 patients treated for advanced aggressive periodontitis and in a supportive maintenance program for a period between 12 and 240 months at implant surgery, a total of 68 non-submerged dental implants were installed. Patients had a plaque score below 20%, and less than 20% of the pockets around the teeth were bleeding on probing (BOP). Using DNA-probes (micro-IDent), the presence and concentration of five periodontal pathogens (Actinobacillus actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Tannerella forsythensis (Tf) and Treponema denticola (Td)) were determined in the five deepest pockets of the rest dentition pre-operatively and after 6 months as well as five places around each implant 10 days, 1 month, 3 months and 6 months after surgery. In each patient, a test to determine the genotype interleukin-1 (IL-1) was performed (PST - micro-IDent). After 6 months, no difference in microbial composition as compared with baseline was found around the teeth in five patients, in 12 minute differences and in five patients important differences were observed. Ten days after surgery, three patients had a complete similar bacterial composition between teeth and implants. In 14 patients, the composition was fairly similar, while large differences in composition and concentration occurred in five patients. This microbiota around the implants remained almost unchanged over a 6-month period and did not hamper the clinical and radiographic osseointegration and did not lead to peri-implantitis, mucositis or initiation of bone destruction. PMID:16441780

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

    PubMed Central

    Leite, Rafaela Torres Portugal; Nogueira, Sarah de Oliveira; do Nascimento, João Paulo Rodrigues; de Lima, Laisa Soares; da Nóbrega, Taís Bastos; Virgínio, Mariana da Silva; Moreno, Lucas Monte da Costa; Sampaio, Bruno Henrique Barbosa; Souza, Fábio Gomes de Matos e

    2015-01-01

    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.

  12. Genome-Wide Association Scan for Variants Associated with Early-Onset Prostate Cancer

    PubMed Central

    Lange, Ethan M.; Johnson, Anna M.; Wang, Yunfei; Zuhlke, Kimberly A.; Lu, Yurong; Ribado, Jessica V.; Keele, Gregory R.; Li, Jin; Duan, Qing; Li, Ge; Gao, Zhengrong; Li, Yun; Xu, Jianfeng; Isaacs, William B.; Zheng, Siqun; Cooney, Kathleen A.

    2014-01-01

    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. PMID:24740154

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

    PubMed

    Leite, Rafaela Torres Portugal; Nogueira, Sarah de Oliveira; do Nascimento, João Paulo Rodrigues; de Lima, Laisa Soares; da Nóbrega, Taís Bastos; Virgínio, Mariana da Silva; Moreno, Lucas Monte da Costa; Sampaio, Bruno Henrique Barbosa; Souza, Fábio Gomes de Matos E

    2015-01-01

    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. PMID:26097750

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

    PubMed

    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. PMID:24456685

  15. Early-onset absence epilepsy aggravated by valproic acid: a video-EEG report.

    PubMed

    Belcastro, Vincenzo; Caraballo, Roberto Horacio; Romeo, Antonino; Striano, Pasquale

    2013-12-01

    Early-onset absence epilepsy refers to patients with absence seizures beginning before age 4 and comprises a heterogeneous group of epilepsies. Onset of absence seizures in the first year of life is very rare. We report a boy with absence seizures with onset at age 11 months, whose seizures increased in frequency after the introduction of valproic acid (VPA) treatment and substantially improved upon cessation of treatment. The mechanism of seizure worsening did not involve VPA toxicity, encephalopathy, Glut-1 deficiency or overdosage, and the reason for absence seizure aggravation remained unclear. The patient showed complete control of absence seizures with levetiracetam treatment and the course was benign, both in terms of seizure control and neuropsychological aspects. The similar overall electroclinical picture and outcome between children with early-onset absences and those with CAE support the view that these conditions are a continuum within the wide spectrum of IGE. [Published with video sequences]. PMID:24169439

  16. Genome-wide association study of recurrent early-onset major depressive disorder

    Microsoft Academic Search

    J Shi; J B Potash; J A Knowles; M M Weissman; W Coryell; W A Scheftner; W B Lawson; J R DePaulo; P V Gejman; A R Sanders; J K Johnson; P Adams; S Chaudhury; D Jancic; O Evgrafov; A Zvinyatskovskiy; N Ertman; M Gladis; K Neimanas; M Goodell; N Hale; N Ney; R Verma; D Mirel; P Holmans; D F Levinson

    2011-01-01

    A genome-wide association study was carried out in 1020 case subjects with recurrent early-onset major depressive disorder (MDD) (onset before age 31) and 1636 control subjects screened to exclude lifetime MDD. Subjects were genotyped with the Affymetrix 6.0 platform. After extensive quality control procedures, 671 424 autosomal single nucleotide polymorphisms (SNPs) and 25 068 X chromosome SNPs with minor allele

  17. Apolipoprotein E4 allele in a population-based study of early-onset Alzheimer's disease

    Microsoft Academic Search

    Duijn van C. M; Peter de Knijff; Marc Cruts; Anita Wehnert; Louis M. Havekes; Broeckhoven van C; A. Hofman

    1994-01-01

    Several studies have reported an association of the apolipoprotein E allele epsilon 4 (APOE*4) to familial and sporadic late-onset Alzheimer's disease (LOAD). Here we report on the relationship between APOE*4 and early-onset Alzheimer's disease (EOAD) in a Dutch population-based study. The frequency of the APOE*4 allele was 2.3 times higher among EOAD cases compared to controls. Among patients, the allele

  18. Neonatal sepsis in the neonatal intensive care unit: characteristics of early versus late onset

    Microsoft Academic Search

    Jia-Horng Jiang; Nan-Chang Chiu; Fu-Yang Huang; Hsin-An Kao; Chyong-Hsin Hsu; Han-Yang Hung; Jui-Hsing Chang; Chun-Chih Peng

    2004-01-01

    episodes of sepsis and 353 isolated pathogens were identified and included in the study. The male-to-female ratio was 1.4. The majority of cases of sepsis occurred in low birth weight (75.9%) and premature babies (76.7%). Late on- set occurred in 71.9% of cases. Patients with late onset had a lower mortality rate than those with early onset (11.3% vs 28.9%).

  19. Types of Periodontal Disease

    MedlinePLUS

    Types of Periodontal Disease Gingivitis Chronic Periodontitis Aggressive Periodontitis Periodontitis Caused by Conditions of the Body Necrotizing Periodontal Diseases Periodontal disease can refer to any condition that affects the gums and ...

  20. Reduced antioxidant defense in early onset first-episode psychosis: a case-control study

    PubMed Central

    2011-01-01

    Background Our objective is to determine the activity of the antioxidant defense system at admission in patients with early onset first psychotic episodes compared with a control group. Methods Total antioxidant status (TAS) and lipid peroxidation (LOOH) were determined in plasma. Enzyme activities and total glutathione levels were determined in erythrocytes in 102 children and adolescents with a first psychotic episode and 98 healthy controls. Results A decrease in antioxidant defense was found in patients, measured as decreased TAS and glutathione levels. Lipid damage (LOOH) and glutathione peroxidase activity was higher in patients than controls. Our study shows a decrease in the antioxidant defense system in early onset first episode psychotic patients. Conclusions Glutathione deficit seems to be implicated in psychosis, and may be an important indirect biomarker of oxidative stress in early-onset schizophrenia. Oxidative damage is present in these patients, and may contribute to its pathophysiology. PMID:21320302

  1. Early onset of puberty and early ovarian failure in CYP7B1 knockout mice.

    PubMed

    Omoto, Yoko; Lathe, Richard; Warner, Margaret; Gustafsson, Jan-Ake

    2005-02-22

    CYP7B1 is the enzyme responsible for hydroxylation and termination of the estrogenic actions of the androgen metabolite, 5alpha-androstane-3beta, 17beta-diol (3betaAdiol). 3betaAdiol is estrogenic in ERalpha or ERbeta positive cells only if they do not express CYP7B1. In this study we show that female CYP7B1(-/-) mice experience early onset of growth of the uterus and mammary glands and commence estrus cycles 2 days earlier than their wild-type littermates. Adult mammary glands and uteri appear to be under continuous estrogenic stimulation. We conclude that, by cell-specific regulation of the estrogenicity of 3betaAdiol, CYP7B1 performs two major tasks: (i) it allows 3betaAdiol to have growth inhibitory effects through ERbeta and (ii) it permits estradiol-specific activation of estrogen receptors by protection of certain cells from the estrogenic effects of 3betaAdiol. When CYP7B1 is inactivated, 3betaAdiol activates estrogen receptors indiscriminately, and the overall effect is prolonged and inappropriate exposure to estrogen. PMID:15710898

  2. Simultaneous Copy Number Losses within Multiple Subtelomeric Regions in Early-Onset Type2 Diabetes Mellitus

    PubMed Central

    Kodama, Shinjiro; Yamada, Tetsuya; Imai, Junta; Sawada, Shojiro; Takahashi, Kei; Tsukita, Sohei; Kaneko, Keizo; Uno, Kenji; Ishigaki, Yasushi; Oka, Yoshitomo; Katagiri, Hideki

    2014-01-01

    Genetic factors play very important roles in the onset and progression of type 2 diabetes mellitus (T2DM). However, the genetic factors correlating with T2DM onset have not as yet been fully clarified. We previously found that copy number losses in the subtelomeric region on chromosome 4p16.3 were detected in early-onset Japanese T2DM patients (onset age <35 years) at a high frequency. Herein, we additionally found two novel copy number losses within the subtelomeric regions on chromosomes 16q24.2-3 and 22q13.31-33, which have significant associations with early-onset Japanese T2DM. The associations were statistically significant by Fisher's exact tests with P values of 5.19×10?3 and 1.81×10?3 and odds ratios of 5.7 and 4.4 for 16q24.2-3 and 22q13.31-33, respectively. Furthermore, copy number variation (CNV) analysis of the whole genome using the CNV BeadChip system verified simultaneous copy number losses in all three subtelomeric regions in 11 of our 100 T2DM subjects, while none of 100 non-diabetic controls showed the copy number losses in all three regions. Our results suggest that the mechanism underlying induction of CNVs is involved in the pathogenesis of early-onset T2DM. Thus, copy number losses within multiple subtelomeric regions are strongly associated with early-onset T2DM and examination of simultaneous CNVs in these three regions may lead to the development of an accurate and selective procedure for detecting genetic susceptibility to T2DM. PMID:24709989

  3. The onset of galactic winds in early-type galaxies

    NASA Technical Reports Server (NTRS)

    Jones, Christine

    1992-01-01

    We completed the spectral analysis of 31 early-type galaxies to investigate whether their x-ray emission was predominantly due to thermal bremsstrahlung from a hot gaseous corona or emission from discrete, galactic sources such as x-ray binaries. If a corona dominates the x-ray emission, its spectra is expected to be relatively cool (0.5 - 1 keV) compared to the harder emission associated with x-ray binaries in our galaxy, the Magellanic Clouds and M31. While it is generally accepted that the x-ray emission in luminous E and S0 galaxies arises from hot coronae, the status of hot gas in lower luminosity (and hence lower mass) galaxies is less clear. Calculations show that, for a given supernova rate, a critical galaxy luminosity (mass) exists below which the gas cannot be gravitationally confined and a galactic wind is predicted to be effective in expelling gas from the galaxy. Since significant mass (a dark halo) is required to hold a hot, gaseous corona around a galaxy, we expect that the faintest, smallest galaxies will not have a hot corona, but their x-ray emission will be dominated by galactic sources or by an active galactic nuclei. In the sample we tested which spanned the absolute magnitude range from -21.5 to -19.5, we found that except for two galaxies whose x-ray emission was dominated by an active nucleus, that the others were consistent with emission from hot gas. We also found that there is a correlation between gas temperature and galaxy magnitude (mass), such that the brighter, more luminous galaxies have hotter gas temperatures. Thus even at relatively faint magnitudes, the dominant emission from early-type galaxies appears to be hot gas. We also carried out an investigation of the x-ray surface brightness distribution of the x-ray emission for about 100 early type galaxies to determine whether the x-ray emission from galaxies are extended. Extended x-ray emission is expected if the emission is due to a hot gaseous corona. We determined the ratio of the source counts in two annuli (0-80 arc seconds and 80-160 arc seconds) for each galaxy and analyzed these ratios using a maximum likelihood estimator to determine the errors on the ratios. Even for weak sources, this ratio provides a sensitive test for source extent. We then compared these ratios to a sample of quasars (all unresolved sources) and have determined which galaxies are extended and which are consistent with point sources. A first paper including the Einstein x-ray fluxes for 147 early-type galaxies has been published in the Astrophysical Journal Supplement Series (with Roberts, Hogg, Bregman, Forman entitled 'Interstellar Matter in Early-Type Galaxies'). A second paper will describe the spectral and extent analysis carried out for this galaxy sample. These results also have been presented at scientific conferences and in colloquia.

  4. Early onset seizures and Rett-like features associated with mutations in CDKL5.

    PubMed

    Evans, Julie C; Archer, Hayley L; Colley, James P; Ravn, Kirstine; Nielsen, Jytte Bieber; Kerr, Alison; Williams, Elizabeth; Christodoulou, John; Gécz, Jozef; Jardine, Philip E; Wright, Michael J; Pilz, Daniela T; Lazarou, Lazarus; Cooper, David N; Sampson, Julian R; Butler, Rachel; Whatley, Sharon D; Clarke, Angus J

    2005-10-01

    Mutations in the CDKL5 gene (also known as STK9) have recently been shown to cause early onset epilepsy and severe mental retardation (ISSX or West syndrome). Patients with CDKL5 mutations sometimes also show features similar to those seen in Rett Syndrome (RTT). We have screened the CDKL5 gene in 94 patients with RTT or a RTT-like phenotype who had tested negative for MECP2 mutations (13 classical RTT female subjects, 25 atypical RTT female subjects, 40 RTT-like female and 16 RTT-like male subjects; 33 of the patients had early onset seizures). Novel pathogenic CDKL5 mutations were identified in three girls, two of whom had initially been diagnosed with the early onset seizure variant of RTT and the other with early onset seizures and some features of RTT. In addition, the 33 patients with early seizures were screened for the most common mutations in the ARX gene but none were found. Combining our three new cases with the previously published cases, 13/14 patients with CDKL5 mutations presented with seizures before the age of 3 months. PMID:16015284

  5. Approach to the Girl with Early Onset of Pubic Hair

    PubMed Central

    Sopher, Aviva B.; Gerken, Adrienne T.

    2011-01-01

    Premature pubarche, or the development of pubic hair before the age of 8 in girls or 9 in boys, is most commonly caused by premature adrenarche. Adrenarche is the maturation of the adrenal zona reticularis in both boys and girls, resulting in the development of pubic hair, axillary hair, and adult apocrine body odor. Although originally thought to be a benign variant of normal development, premature adrenarche has been associated with insulin resistance and the later development of metabolic syndrome and polycystic ovary syndrome. Although further studies are needed to confirm these relationships, the case presented herein argues for periodic assessment of children at risk. Indeed, recognition of these associations may allow for early preventive measures. PMID:21602454

  6. Reconceptualizing Early- and Late-Onset: A Life Course Analysis of Older Heroin Users

    PubMed Central

    Boeri, Miriam Williams; Sterk, Claire E.; Elifson, Kirk W.

    2013-01-01

    Purpose Our knowledge regarding older users of illicit drugs is limited despite their increasing numbers. In this paper we apply a life course perspective to gain a further understanding of older adult drug use, specifically contrasting early- and late-onset heroin users. Design and Methods Qualitative data were collected from 29 older heroin users. Life course analysis focused on the users’ experiences across the life span. Results The findings suggest that those aging-into heroin use (late-onset) are disadvantaged compared to those who are maturing-in (early-onset) except in areas of health. Implications We propose that conceptualizing the use of heroin and other illicit drugs among older adults based on their life course trajectory will provide insights for social and health services, including drug treatment. PMID:18981280

  7. A presenilin-1 mutation (T245P) in transmembrane domain 6 causes early onset Alzheimer's disease.

    PubMed

    Edwards-Lee, Terri; Wen, Johnny; Bell, Jason; Hardy, John; Chung, Julia; Momeni, Parastoo

    2006-05-01

    We report a presenilin-1 mutation (T245P) in a Japanese-American family with autosomal dominant Alzheimer's disease with an onset age in the early 40s. The early clinical features were remarkable for their purely amnestic nature. The position of the mutation is in the transmembrane domain that harbors the aspartic acid residue which is believed to be part of the active site of gamma-secretase. PMID:16469444

  8. The Effects of Childhood ADHD Symptoms on Early-Onset Substance Use: A Swedish Twin Study

    ERIC Educational Resources Information Center

    Chang, Zheng; Lichtenstein, Paul; Larsson, Henrik

    2012-01-01

    Research has documented that children and adolescents with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of substance use problems. Few studies, however, have focused on early-onset substance use. This study therefore investigated how the two symptom dimensions of ADHD (hyperactivity/impulsivity and inattention) are…

  9. Child and adolescent (early onset) schizophrenia: A review in light of DSM-III-R

    Microsoft Academic Search

    John S. Werry

    1992-01-01

    Early onset schizophrenia (EOS) is defined as that beginning in childhood or adolescence (under 16 or 17). Studies of EOS are infrequent, and comparative adult figures not always available, but tentative conclusions may be drawn. EOS is more common in males; symptomatology is often undifferentiated; frequencies of homotypic family disorder, premorbid schizotypal personality, and neurodevelopmental abnormalities high; outcome poor but

  10. Early detection of axonal and neuronal lesions in prenatal-onset periventricular leukomalacia

    Microsoft Academic Search

    Shu Zhen Meng; Yasuhiro Arai; Kimiko Deguchi; Sachio Takashima

    1997-01-01

    The expression of ?-amyloid precursor protein (?-APP) immunoreactivity was investigated in 16 cases of prenatal-onset periventricular leukomalacia (PVL). ?-APP positive axons were found in the early stage of prenatal PVL, which included coagulation necrosis, microglial activation, axonal swelling or astrogliosis, but were not detectable in the late stage of prenatal PVL. Furthermore, ?-APP immunoreactive neurons were also observed in the

  11. Antepartum use of antibiotics and early-onset neonatal sepsis: The next 4 years

    Microsoft Academic Search

    Craig V. Towers; Gerald G. Briggs

    2002-01-01

    Objective: The purpose of this study was to analyze the incidence of early-onset neonatal sepsis and the presence of antibiotic resistance of the isolated bacteria and its relationship to antibiotic chemoprophylaxis that occurred during the 4 years that followed the publication of the most recent group B streptococcal guidelines. Study Design: A prospective cohort study was performed between January 1,

  12. Impact of DNA Testing for Early-Onset Familial Alzheimer Disease and Frontotemporal Dementia

    Microsoft Academic Search

    Ellen J. Steinbart; Corrine O. Smith; Parvoneh Poorkaj; Thomas D. Bird

    2001-01-01

    Background: DNA testing of persons at risk for heredi- tary, degenerative neurologic diseases is relatively new. Only anecdotal reports of such testing in familial Alz- heimer disease (FAD) exist, and little is know about the personal and social impact of such testing. Methods: In a descriptive, observational study, indi- viduals at 50% risk for autosomal dominant, early-onset FAD or frontotemporal

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

    ERIC Educational Resources Information Center

    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…

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

    PubMed Central

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

    2013-01-01

    Mutations in CDKL5 and ARX are known causes of early-onset epilepsy and severe developmental delay in males and females. While 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 ten 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. The 18 patients include eight new males with CDKL5 mutations and ten with ARX mutations identified through sequence analysis of 266 and 346 males, respectively, at our molecular diagnostic laboratory. Our large data set 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. PMID:23583054

  15. Enhanced Visual Speech Perception in Individuals with Early-Onset Hearing Impairment

    ERIC Educational Resources Information Center

    Auer, Edward T., Jr.; Bernstein, Lynne E.

    2007-01-01

    Purpose: L. E. Bernstein, M. E. Demorest, and P. E. Tucker (2000) demonstrated enhanced speechreading accuracy in participants with early-onset hearing loss compared with hearing participants. Here, the authors test the generalization of Bernstein et al.'s (2000) result by testing 2 new large samples of participants. The authors also investigated…

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

    PubMed

    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. PMID:23583054

  17. Is a child's risk of early onset schizophrenia increased in the highest social class?

    Microsoft Academic Search

    Taru Mäkikyrö; Matti Isohanni; Juha Moring; Hannu Oja; Helinä Hakko; Peter Jones; Paula Rantakallio

    1997-01-01

    In a sample from the unselected, general population Northern Finland 1966 Birth Cohort, 11 017 individuals alive at the age of 16 years were studied until the age of 27. The cumulative incidence of early onset schizophrenia until 23 years was higher (1.14%; 9\\/792) among young persons from the highest social class or class I (determined according to father's occupation)

  18. Functional Connectivity of the Amygdala in Early-Childhood-Onset Depression

    ERIC Educational Resources Information Center

    Luking, Katherine R.; Repovs, Grega; Belden, Andy C.; Gaffrey, Michael S.; Botteron, Kelly N.; Luby, Joan L.; Barch, Deanna M.

    2011-01-01

    Objective: Adult major depressive disorder (MDD) is associated with reduced cortico-limbic functional connectivity thought to indicate decreased top-down control of emotion. However, it is unclear whether such connectivity alterations are also present in early-childhood-onset MDD. Method: A total of 51 children 7 through 11 years of age who had…

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

    ERIC Educational Resources Information Center

    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),…

  20. Developmental Trends and L1 Effects in Early L2 Learners' Onset Cluster Production

    ERIC Educational Resources Information Center

    Tessier, Anne-Michelle; Duncan, Tamara Sorenson; Paradis, Johanne

    2013-01-01

    This study focuses on English onset cluster production in spontaneous speech samples of 10 children aged 5;04-6;09 from Chinese and Hindi/Punjabi first language (L1) backgrounds, each with less than a year of exposure to English. The results suggest commonalities between early second language (L2) learners and both monolingual and adult L2…

  1. Phenotype Variations in Early Onset Pompe Disease: Diagnosis and Treatment Results with Myozyme®

    Microsoft Academic Search

    Samuel Ignacio Pascual Pascual; Pascual Pascual

    \\u000a Pompe disease is a rare autosomal recessive lysosomal storage disease caused by deficiency of acid-a-glucosidase (GAA). This\\u000a deficiency results in glycogen accumulation in the lysosomes, leading to lysosomal swelling, cellular damage and organ dysfunction.\\u000a Patient age at the onset of Pompe disease symptoms and the rate of deterioration can vary considerably.\\u000a \\u000a \\u000a In early onset patients (the classical infantile form) this

  2. DJ1 analysis in a large cohort of Italian early onset Parkinson Disease patients?

    PubMed Central

    Sironi, Francesca; Primignani, Paola; Ricca, Sara; Tunesi, Sara; Zini, Michela; Tesei, Silvana; Cilia, Roberto; Pezzoli, Gianni; Seia, Manuela; Goldwurm, Stefano

    2013-01-01

    We analyzed the DJ1 gene in a large consecutive series (N = 163) of Italian unrelated Early Onset Parkinson Disease (EOPD: onset ?40 years of age) patients and 100 healthy controls (mean age 64 ± 7 years). No homozygous or compound heterozygous mutations with an obvious pathogenic effect were found. Several variants were identified, some of which were novels. All variants had similar frequency in patients and in controls. Our data suggest that DJ1 mutations are very rare in Italian EOPD. Other genes and risk factors for PD are still to be identified. PMID:24176883

  3. Toll-Like Receptor 2 Gene Polymorphisms Associated with Aggressive Periodontitis in Japanese

    PubMed Central

    Takahashi, Marika; Chen, Zhiyong; Watanabe, Kaoru; Kobayashi, Hiroaki; Nakajima, Toshiaki; Kimura, Akinori; Izumi, Yuichi

    2011-01-01

    Background and Objective: Aggressive periodontitis is a rare and very severe periodontal disease of early onset, which is closely associated with Porphyromonas.gingivalis (P.g.) infection in the Japanese population. TLR2 encodes Toll-like receptor 2, which plays an important role in the protective response to P.g. infection. We investigated a possible association between TLR2 and aggressive periodontitis. Material and Methods: Of 2,460 Japanese patients with periodontitis, 38 patients with aggressive periodontitis were enrolled in this study. These 38 aggressive periodontitis patients and 190 Japanese healthy controls were examined for an insertion/deletion (Ins/Del) polymorphism in exon 1, a polymorphism in intron 1 (rs7696323), and a synonymous polymorphism in exon 3 (rs3804100) in TLR2. Results: We found significant associations of resistance to aggressive periodontitis with the Ins allele (allele frequency in the patients versus controls, 0.540 vs. 0.676, OR=0.56, 95% confidence interval (CI); 0.34-0.92, p=0.022) and the T allele of rs3804100 (0.579 vs. 0.716, OR=0.55, 95% CI; 0.33-0.91, p=0.018), although the C allele of rs7696323 showed no significant association (0.733 vs. 0.829, OR=0.58). A permutation test of Ins/Del-rs7696323-rs3804100 haplotype revealed a significant association between Ins-C-T haplotype (0.252 vs. 0.479, p=0.0003) and resistance to aggressive periodontitis. Conclusions: The TLR2 polymorphisms were suggested to confer protection against aggressive periodontitis in a Japanese population. The association should be replicated in other cohorts to further identify the responsible TLR polymorphism(s) involved in the pathogenesis of aggressive periodontitis. PMID:22235236

  4. Periodontal Plastic Surgery

    MedlinePLUS

    ... the teeth and to recreate a normal appearance. Periodontal Disease Periodontal disease is diagnosed when gingival or gum ... changes and extending to periodontal plastic surgery. Treating Periodontal Disease Periodontal disease does not always respond to conservative ...

  5. Onset to First Alcohol Use in Early Adolescence: A Network Diffusion Model

    PubMed Central

    Light, John M.; Greenan, Charlotte C.; Rusby, Julie C.; Nies, Kimberley M.; Snijders, Tom A.B.

    2013-01-01

    A novel version of Snijders’s stochastic actor-based modeling (SABM) framework is applied to model the diffusion of first alcohol use through middle school-wide longitudinal networks of early adolescents, aged approximately 11–14 years. Models couple a standard SABM for friendship network evolution with a proportional hazard model for first alcohol use. Meta-analysis of individual models for 12 schools found significant effects for friendship selection based on the same alcohol use status, and for an increased rate of onset to first use based on exposure to already-onset peers. Onset rate was greater at higher grades and among participants who spent more unsupervised time with friends. Neither selection nor exposure effects interacted with grade, adult supervision, or gender. PMID:24039379

  6. Onset to First Alcohol Use in Early Adolescence: A Network Diffusion Model.

    PubMed

    Light, John M; Greenan, Charlotte C; Rusby, Julie C; Nies, Kimberley M; Snijders, Tom A B

    2013-09-01

    A novel version of Snijders's stochastic actor-based modeling (SABM) framework is applied to model the diffusion of first alcohol use through middle school-wide longitudinal networks of early adolescents, aged approximately 11-14 years. Models couple a standard SABM for friendship network evolution with a proportional hazard model for first alcohol use. Meta-analysis of individual models for 12 schools found significant effects for friendship selection based on the same alcohol use status, and for an increased rate of onset to first use based on exposure to already-onset peers. Onset rate was greater at higher grades and among participants who spent more unsupervised time with friends. Neither selection nor exposure effects interacted with grade, adult supervision, or gender. PMID:24039379

  7. A Japanese girl with an early-infantile onset vanishing white matter disease resembling Cree leukoencephalopathy.

    PubMed

    Takano, Kyoko; Tsuyusaki, Yu; Sato, Mutsumi; Takagi, Mariko; Anzai, Rie; Okuda, Mitsuko; Iai, Mizue; Yamashita, Sumimasa; Okabe, Tetsuhiko; Aida, Noriko; Tsurusaki, Yoshinori; Saitsu, Hirotomo; Matsumoto, Naomichi; Osaka, Hitoshi

    2015-06-01

    Vanishing white matter disease (VWM)/childhood ataxia with central hypomyelination (CACH) is an autosomal recessive leukoencephalopathy caused by mutations in one of five genes, EIF2B1-5, encoding the 5 subunits of eukaryotic translation initiation factor 2B (eIF2B). The classical phenotype is characterized by early childhood onset and chronic progressive neurological deterioration with cerebellar ataxia, spasticity, optic atrophy and epilepsy. However, the onset of disease varies from antenatal period to adulthood. Cree leukoencephalopathy (CLE) is a severe variant of VWM and caused by a homozygous mutation (R195H) in the EIF2B5 gene. The patient reported in this study developed lethargy, vomiting and seizure 3days after an oral poliovirus vaccination at the age of 4months. She presented with rapid neurological deterioration within a month of onset. Brain MRI showed abnormal white matter intensity. Whole-exome sequencing identified two heterozygous mutations in the EIF2B5 gene: a known mutation, c.584G>A (R195H, which is homozygous in CLE), and a novel mutation, c.1223T>C (I408T, which resides in the "I-patch"). Mutations in the "I-patch" encoded region of eIF2B? may be related to an early-infantile onset phenotype. This patient exhibits an early-infantile onset and progressive disease course resembling CLE, suggesting a severe functional disruption of eIF2B? caused by R195H as well as by I408T mutations. PMID:25457085

  8. Early onset pneumonia following pulmonary contusion: the case of Stonewall Jackson.

    PubMed

    Lively, Mathew W

    2012-03-01

    Confederate Lieutenant General Thomas J. "Stonewall" Jackson was wounded by his own men at the Battle of Chancellorsville during the American Civil War. While being removed from the field, Jackson fell from the litter and struck the right side of his chest on a large stone or stump. Four days following the amputation of his left arm, Jackson developed pneumonia in his right lung. His treating physicians believed the infection developed secondary to a pulmonary contusion that occurred when he fell from the litter. Pulmonary contusions are an independent risk factor in the development of post-traumatic pneumonia and an infection that occurs within 72 to 96 hours of injury is termed an early onset pneumonia. The nature and timing of Stonewall Jackson's illness following his wounding is consistent with the modem diagnosis of early onset pneumonia following chest trauma. PMID:22479920

  9. A small Askin's tumor presenting with early onset of chest pain.

    PubMed

    Jeong, Jin Yong; Kim, Sang Yong; Jeong, Dae Chul; Kim, Ki Jun

    2015-01-01

    Most primitive neuroectodermal tumor of the chest wall destroy the rib, chest wall muscles, diaphragm, and lung or extend into the spinal compartment, resulting in a large-sized tumor and symptoms. In contrast, we recently encountered a rare case of Askin's tumor presenting with early-onset chest pain despite the small size. After resection of the tumor and adjuvant chemotherapy, the patient remains disease-free over 3 years of follow-up. PMID:25884603

  10. Living at Risk: The Sibling’s Perspective of Early-Onset Alzheimer’s Disease

    Microsoft Academic Search

    Karen E. Wain; Wendy R. Uhlmann; Judith Heidebrink; J. Scott Roberts

    2009-01-01

    Early-onset Alzheimer’s disease (EOAD) is an increasingly diagnosed condition and is associated with genetic risk factors.\\u000a This is one of the first studies exploring the lived experience of siblings of individuals with EOAD. We used structured questionnaires\\u000a and semi-structured interviews to assess a broad range of siblings’ experiences with and beliefs about EOAD, including knowledge,\\u000a perceptions of personal risk, level

  11. Development and assessment issues in the diagnosis of early-onset bipolar disorder 

    E-print Network

    George, Carrie Anne

    2005-11-01

    : School Psychology iii ABSTRACT Development and Assessment Issues in the Diagnosis of Early-Onset Bipolar Disorder. (August 2004) Carrie George, B.A., Southwestern University; M.A., St. Mary?s University Chair of Advisory Committee: Dr. Cynthia Riccio... disorders in children, specifically depression, mania, and bipolar disorder. Depression can be viewed as a symptom or a syndrome. As a symptom, it is a general feeling of unhappiness. As a syndrome, depression is a psychiatric disorder characterized by a...

  12. Diagnostic and Sex Effects on Limbic Volumes in Early-Onset Bipolar Disorder and Schizophrenia

    Microsoft Academic Search

    Jean A. Frazier; Steven M. Hodge; Janis L. Breeze; Anthony J. Giuliano; Janine E. Terry; Constance M. Moore; David N. Kennedy; Melissa P. Lopez-Larson; Verne S. Caviness; Larry J. Seidman; Benjamin Zablotsky; Nikos Makris

    2008-01-01

    Objective: The limbic structures in early-onset schizophre- nia-spectrum illness (SZ) and bipolar disorder (BPD) were studied to discern patterns associated with diagnosis and sex. Methods: Thirty-five youths with DSM-IV BPD with- outpsychosis,19 with BPD withpsychosis, 20with SZ, and 29 healthy controls (HC), similar in age (6-17 years) and sex,underwent structuredand clinicalinterviews,neurolog- icalexamination,andcognitivetesting.Structuralmagnetic resonance images (MRIs) were acquired on a 1.5

  13. Inflammatory Mediators in Umbilical Plasma from Neonates Who Develop Early-Onset Sepsis

    Microsoft Academic Search

    Henrik Døllner; Lars Vatten; Ingjerd Linnebo; Gro Flatabø Zanussi; Åge Lærdal; Rigmor Austgulen

    2001-01-01

    Objectives: To study whether early-onset neonatal sepsis is associated with a prenatal immune response with elevated umbilical plasma levels of inflammatory mediators, and to study whether mediator levels may be helpful in identifying infected neonates. Setting: Nested case-control study. Methods: Cord blood was sampled from 7,073 consecutively delivered neonates. After review of the medical records, neonates suspected to suffer from

  14. Early-Onset Neonatal Sepsis in the Era of Group B Streptococcal Prevention

    Microsoft Academic Search

    Robert S. Baltimore; Sharon M. Huie; James I. Meek; Anne Schuchat; Katherine L. O'Brien

    Objective. To determine whether intra- partum antibiotic prophylaxis for neonatal group B strep- tococcal (GBS) disease has resulted in an increased rate of non-GBS or antibiotic-resistant early-onset invasive neonatal disease. Methods. Maternal and infant chart review of all in- fants with bacteria other than GBS isolated from blood or spinal fluid in 1996 through 1999 in 19 hospitals (repre- senting

  15. Course of intelligence deficits in early onset, first episode schizophrenia: a controlled, 5-year longitudinal study

    Microsoft Academic Search

    Jens Richardt Moellegaard Jepsen; Birgitte Fagerlund; Anne Katrine Pagsberg; Anne Marie R. Christensen; Rikke W. Hilker; Merete Nordentoft; Erik L. Mortensen

    2010-01-01

    Only few prospective longitudinal studies have assessed the course of intelligence deficits in early onset schizophrenia (EOS),\\u000a and these have used different age appropriate versions of Wechsler Intelligence Scales and age appropriate norms. The post-psychotic\\u000a development of intelligence in EOS has predominantly been characterized as relatively stable in these studies. However, comparisons\\u000a of IQs from different test versions based on

  16. Early onset seizures and Rett-like features associated with mutations in CDKL5

    Microsoft Academic Search

    Julie C Evans; Hayley L Archer; James P Colley; Kirstine Ravn; Jytte Bieber Nielsen; Alison Kerr; Elizabeth Williams; John Christodoulou; Jozef Gécz; Philip E Jardine; Michael J Wright; Daniela T Pilz; Lazarus Lazarou; David N Cooper; Julian R Sampson; Rachel Butler; Sharon D Whatley; Angus J Clarke

    2005-01-01

    Mutations in the CDKL5 gene (also known as STK9) have recently been shown to cause early onset epilepsy and severe mental retardation (ISSX or West syndrome). Patients with CDKL5 mutations sometimes also show features similar to those seen in Rett Syndrome (RTT). We have screened the CDKL5 gene in 94 patients with RTT or a RTT-like phenotype who had tested

  17. Canadian patient played key role in uncovering secrets about early-onset Alzheimer's disease.

    PubMed

    Lyttle, J

    1996-03-15

    Last June, the University of Toronto announced that Canadian scientists and a team of international researchers had discovered the gene responsible for most cases of early-onset Alzheimer's disease. One of the key players in that discovery had died just 3 months earlier. Frances Hodge, who participated in a battery of tests for the 20 years she lived with the disease, helped lead researchers to gene S182--and an ember of hope for future generations. PMID:8634971

  18. Gender Differences in the Interpersonal Consequences of Early-Onset Depressive Symptoms

    Microsoft Academic Search

    Karen D. Rudolph; Gary W. Ladd; Lisa. Dinella

    2007-01-01

    Although research has identified gender differences in the interpersonal antecedents of depressive symptoms in youth, little is known about gender differences in the interpersonal consequences of depression. The goal of the present research was to examine gender differences in the influence of early-onset depressive symptoms on adolescent friendships and self-perceived peer acceptance. Third-graders (N = 382) participated in a multiwave

  19. Early onset of vegetation growth vs. rapid green-up: impacts on juvenile mountain ungulates.

    PubMed

    Pettorelli, Nathalie; Pelletier, Fanie; Von Hardenberg, Achaz; Festa-Bianchet, Marco; Côté, Steeve D

    2007-02-01

    Seasonal patterns of climate and vegetation growth are expected to be altered by global warming. In alpine environments, the reproduction of birds and mammals is tightly linked to seasonality; therefore such alterations may have strong repercussions on recruitment. We used the normalized difference vegetation index (NDVI), a satellite-based measurement that correlates strongly with aboveground net primary productivity, to explore how annual variations in the timing of vegetation onset and in the rate of change in primary production during green-up affected juvenile growth and survival of bighorn sheep (Ovis canadensis), Alpine ibex (Capra ibex), and mountain goats (Oreamnos americanus) in four different populations in two continents. We indexed timing of onset of vegetation growth by the integrated NDVI (INDVI) in May. The rate of change in primary production during green-up (early May to early July) was estimated as (1) the maximal slope between any two successive bimonthly NDVI values during this period and (2) the slope in NDVI between early May and early July. The maximal slope in NDVI was negatively correlated with lamb growth and survival in both populations of bighorn sheep, growth of mountain goat kids, and survival of Alpine ibex kids, but not with survival of mountain goat kids. There was no effect of INDVI in May and of the slope in NDVI between early May and early July on juvenile growth and survival for any species. Although rapid changes in NDVI during the green-up period could translate into higher plant productivity, they may also lead to a shorter period of availability of high-quality forage over a large spatial scale, decreasing the opportunity for mountain ungulates to exploit high-quality forage. Our results suggest that attempts to forecast how warmer winters and springs will affect animal population dynamics and life histories in alpine environments should consider factors influencing the rate of changes in primary production during green-up and the timing of vegetation onset. PMID:17479756

  20. Rare autosomal copy number variations in early-onset familial Alzheimer's disease.

    PubMed

    Hooli, B V; Kovacs-Vajna, Z M; Mullin, K; Blumenthal, M A; Mattheisen, M; Zhang, C; Lange, C; Mohapatra, G; Bertram, L; Tanzi, R E

    2014-06-01

    Over 200 rare and fully penetrant pathogenic mutations in amyloid precursor protein (APP), presenilin 1 and 2 (PSEN1 and PSEN2) cause a subset of early-onset familial Alzheimer's disease (EO-FAD). Of these, 21 cases of EO-FAD families carrying unique APP locus duplications remain the only pathogenic copy number variations (CNVs) identified to date in Alzheimer's disease (AD). Using high-density DNA microarrays, we performed a comprehensive genome-wide analysis for the presence of rare CNVs in 261 EO-FAD and early/mixed-onset pedigrees. Our analysis revealed 10 novel private CNVs in 10 EO-FAD families overlapping a set of genes that includes: A2BP1, ABAT, CDH2, CRMP1, DMRT1, EPHA5, EPHA6, ERMP1, EVC, EVC2, FLJ35024 and VLDLR. In addition, CNVs encompassing two known frontotemporal dementia genes, CHMP2B and MAPT were found. To our knowledge, this is the first study reporting rare gene-rich CNVs in EO-FAD and early/mixed-onset AD that are likely to underlie pathogenicity in familial AD and perhaps related dementias. PMID:23752245

  1. Approach to early-onset colorectal cancer: Clinicopathological, familial, molecular and immunohistochemical characteristics

    PubMed Central

    Perea, Jose; Alvaro, Edurne; Rodríguez, Yolanda; Gravalos, Cristina; Sánchez-Tomé, Eva; Rivera, Barbara; Colina, Francisco; Carbonell, Pablo; González-Sarmiento, Rogelio; Hidalgo, Manuel; Urioste, Miguel

    2010-01-01

    AIM: To characterize clinicopathological and familial features of early-onset colorectal cancer (CRC) and compare features of tumors with and without microsatellite instability (MSI). METHODS: Forty-five patients with CRC aged 45 or younger were included in the study. Clinical information, a three-generation family history, and tumor samples were obtained. MSI status was analyzed and mismatch repair genes were examined in the MSI families. Tumors were included in a tissue microarray and an immunohistochemical study was carried out with a panel of selected antibodies. RESULTS: Early onset CRC is characterized by advanced stage at diagnosis, right colon location, low-grade of differentiation, mucin production, and presence of polyps. Hereditary forms represent at least 21% of cases. Eighty-one percent of patients who died during follow-up showed a lack of expression of cyclin E, which could be a marker of poor prognosis. ?-catenin expression was normal in a high percentage of tumors. CONCLUSION: Early-onset CRC has an important familial component, with a high proportion of tumors showing microsatellite stable. Cyclin E might be a poor prognosis factor. PMID:20677343

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

    PubMed

    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. PMID:21802232

  3. Regional cerebral blood flow changes in early-onset anorexia nervosa before and after weight gain.

    PubMed

    Komatsu, Hiroko; Nagamitsu, Shinichiro; Ozono, Shuichi; Yamashita, Yushiro; Ishibashi, Masatoshi; Matsuishi, Toyojiro

    2010-09-01

    To investigate the changes of regional cerebral blood flow (rCBF) in early-onset anorexia nervosa (AN) before and after weight gain, we examined resting rCBF using single photon emission computed tomography (SPECT) with [(123)I]iodoamphetamine ((123)I-IMP). Ten female children with AN (mean age 13.2 years old) participated in this study. SPECT examinations were performed in all patients twice at the beginning of treatment and after weight gain. The mean body mass index (BMI) was changed from 13.1 to 16.6 during 4 months treatment period. Automatic voxel-based analysis of the images was carried out using statistical parametric mapping (SPM) software. Relatively increased rCBF in the bilateral parietal lobe and limbic lobe including the posterior cingulate cortex (PCC) were observed after weight gain in early-onset AN. There was no significant decrease in the rCBF after weight gain. A significant positive correlation was observed between BMI and rCBF in the right thalamus, right parietal lobe, and right cerebellum. These results suggested that weight gain during the process of recovery from early-onset AN might activate specific brain regions which are possibly relevant to the pathophysiological aspects of the disorder. PMID:19875256

  4. Early impact basins and the onset of plate tectonics. Ph.D. Thesis - Maryland Univ.

    NASA Technical Reports Server (NTRS)

    Frey, H.

    1977-01-01

    The fundamental crustal dichotomy of the Earth (high and low density crust) was established nearly 4 billion years ago. Therefore, subductable crust was concentrated at the surface of the Earth very early in its history, making possible an early onset for plate tectonics. Simple thermal history calculations spanning 1 billion years show that the basin forming impact thins the lithosphere by at least 25%, and increases the sublithosphere thermal gradients by roughly 20%. The corresponding increase in convective heat transport, combined with the highly fractured nature of the thinned basin lithosphere, suggest that lithospheric breakup or rifting occurred shortly after the formation of the basins. Conditions appropriate for early rifting persisted from some 100,000,000 years following impact. We suggest a very early stage of high temperature, fast spreading "microplate" tectonics, originating before 3.5 billion years ago, and gradually stabilizing over the Archaean into more modern large plate or Wilson Cycle tectonics.

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

    PubMed

    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. PMID:22872100

  6. Early onset APOE E4-negative Alzheimer's disease patients show faster cognitive decline on non-memory domains.

    PubMed

    Smits, Lieke L; Pijnenburg, Yolande A L; van der Vlies, Annelies E; Koedam, Esther L G E; Bouwman, Femke H; Reuling, Ilona E W; Scheltens, Philip; van der Flier, Wiesje M

    2015-07-01

    Age at onset and APOE E4-genotype have been shown to influence clinical manifestation of Alzheimer's disease (AD). We investigated rate of decline in specific cognitive domains according to age at onset and APOE E4-genotype in patients with AD. 199 patients with probable AD underwent at least two annual neuropsychological assessments. Patients were classified according to age-at-onset (?65 years vs >65 years) and APOE genotype (positive vs negative). The neuropsychological test battery compromised tests for memory, language, attention, executive and visuo-spatial functioning. For each domain compound z-scores were calculated, based on the baseline performance of patients. Average duration of follow-up was 1.5±1 years. We used linear mixed models (LMM) to estimate effects of age, APOE and age?APOE on cognitive decline over time. At baseline, patients were 65±8 years, 98(49%) were female and MMSE was 22±4. LMM showed that early onset patients declined faster on executive functioning (?±SE:-0.09±0.06) than late onset patients, but age was not related to decline in the other cognitive domains. APOE E4 negative patients declined faster on language than APOE E4 positive patients (?±SE:-0.1±0.06). When we took age and APOE genotype into account simultaneously, we found that compared to late onset-E4 positive patients, early onset-E4 negative patients declined faster on language (?±SE:-0.36±0.1), attention (?±SE:-0.42±0.1), executive (?±SE:-0.41±0.1) and visuo-spatial functioning (?±SE:-0.43±0.1). Late onset-E4 negative and early onset-E4 positive patients showed intermediate rates of decline. We found no differences in decline on memory. We found that patients who develop AD despite absence of the two most important risk factors, show steepest cognitive decline on non-memory cognitive domains. PMID:25891378

  7. Subgingival microflora and treatment in prepubertal periodontitis associated with chronic idiopathic neutropenia.

    PubMed

    Kamma, J J; Lygidakis, N A; Nakou, M

    1998-09-01

    Prepubertal periodontitis affects both primary and permanent dentition. The purpose of this study was to examine the composition of subgingival microflora of the permanent dentition in an 11-year-old Caucasian female, who had premature exfoliation of her deciduous teeth on her 5th year of age, and the response of this condition to the antibiotic therapy and supportive periodontal care. Gingival tissues were highly inflamed and alveolar bone loss was detected radiographically. The girl had experienced frequent upper respiratory tract infections, tonsilitis and recurrent otitis media. Her mother had history of early onset periodontitis associated with chronic idiopathic neutropenia. Blood chemistry tests and immunological examinations were also performed. Subgingival plaque samples were collected from the proximal sites of permanent molars, incisors, canines and maxillary premolars. 27 different microbial species were isolated from the subgingival microflora. Among the predominant species were Porphyromonas gingivalis (17.6%-7.3%), Prevotella intermedia (12.4%-4.7%), Capnocytophaga sputigena (14.4%-10.4%), Capnocytophaga ochracea (13.2%-6.9%) and Actinobacillus actinomycetemcomitans (9.3%-5.5%). Periodontal treatment consisted of scaling, root planing in conjunction with antibiotic administration of Augmentin 312.5 mg and Flagyl 200 mg, each t.i.d. for 10 days. 3 weeks after the antibiotic therapy, bacterial samples were collected from the same sites. All the periodontal pathogens were recovered in lower levels and A.actinomycetemcomitans was almost eliminated in the 3-week period. The evaluation of clinical indices at 3, 6 and 12 months showed that periodontal treatment in conjunction with antibiotics was effective and rapidly followed by marked clinical improvement. The microbiological monitoring at 3, 6 and 12 months after antibiotic treatment and each time prior to supportive periodontal care, revealed that the periodontal pathogens fluctuated in low levels even 12 months after treatment and could be maintained at low level by supportive periodontal care at 3-month intervals. PMID:9763332

  8. Herlyn–Werner–Wunderlich syndrome: An “earlyonset case report and review of Literature

    PubMed Central

    Angotti, R.; Molinaro, F.; Bulotta, A.L.; Bindi, E.; Cerchia, E.; Sica, M.; Messina, M.

    2015-01-01

    Herlyn–Werner–Wunderlich syndrome (HWWS) is a rare congenital mullerian anomaly consisting of uterus didelphys, hemivaginal septum, and unilateral renal agenesis [1,2]. Most authors reported cases of Herlyn–Werner–Wunderlich syndrome with prepuberal or postpuberal onset with cyclical abdominal pain and a vaginal mass (3–8). Only six cases are reported in Literature with early onset of this syndrome under 5 years (9–14). Our case is about 3 years old girl, with all the features of this syndrome who came to our attention for lower abdominal mass. The aim of this article is to share our experience and focus the attention on the importance of high level of suspicion of HWWS in neonatal period to early diagnosis and treatment. The possible early presentation of this syndrome should be suspected in all neonates (females) with renal agenesia confirmed postnatally or with prenatal diagnosis. It is common, in fact, an error of evaluation with planning of removal of mass, that can damage patients in term of chance for a successful reproductive outcome. For all these reasons, our team consider HWWS as differential diagnosis in newborn with prenatal ultrasonography of a cystic mass behind the urinary bladder in the absence of a kidney and plan a pelvic ultrasound (with aim to identify an uterus, normal or dydhelfus, and presence or absence of pelvic mass), an examination under anesthesia and cystoscopy and vaginoscopy, if it is necessary. A high level of suspicion, indeed, is the key to early diagnosis. PMID:25932973

  9. Genes of early-onset epileptic encephalopathies: from genotype to phenotype.

    PubMed

    Mastrangelo, Mario; Leuzzi, Vincenzo

    2012-01-01

    Early-onset epileptic encephalopathies are severe disorders in which cognitive, sensory, and motor development is impaired by recurrent clinical seizures or prominent interictal epileptiform discharges during the neonatal or early infantile periods. They include Ohtahara syndrome, early myoclonic epileptic encephalopathy, West syndrome, Dravet syndrome, and other diseases, e.g., X-linked myoclonic seizures, spasticity and intellectual disability syndrome, idiopathic infantile epileptic-dyskinetic encephalopathy, epilepsy and mental retardation limited to females, and severe infantile multifocal epilepsy. We summarize recent updates on the genes and related clinical syndromes involved in the pathogenesis of early-onset epileptic encephalopathies: Aristaless-related homeobox (ARX), cyclin-dependent kinase-like 5 (CDKL5), syntaxin-binding protein 1 (STXBP1), solute carrier family 25 member 22 (SLC25A22), nonerythrocytic ?-spectrin-1 (SPTAN1), phospholipase C?1 (PLC?1), membrane-associated guanylate kinase inverted-2 (MAGI2), polynucleotide kinase 3'-phosphatase (PNKP), sodium channel neuronal type 1? subunit (SCN1A), protocadherin 19 (PCDH19), and pyridoxamine 5-prime-phosphate oxidase (PNPO). PMID:22196487

  10. Prospective Associations of Early-Onset Axis I Disorders with Developing Eating Disorders

    PubMed Central

    Sihvola, Elina; Keski-Rahkonen, Anna; Dick, Danielle M.; Hoek, Hans W.; Raevuori, Anu; Rose, Richard J.; Pulkkinen, Lea; Marttunen, Mauri; Kaprio, Jaakko

    2009-01-01

    Objective To study the developmental relationships of adolescent-onset Axis I mental disorders and eating disorders. Method 1318 adolescent twins born 1983-87 completed a professionally administered semi-structured psychiatric interview at age 14 and a questionnaire follow-up at age 17.5. Results Eating disorders at age 17.5 were significantly predicted by major depressive disorder (MDD, odds ratio [OR] 5.9, 95% confidence interval [CI] 2.6-15.3), and generalized anxiety disorders (GAD, OR 4.7, 95% CI 1.8-15.6) at age 14, when baseline eating disorders were excluded. Early-onset MDD in combination with GAD increased the likelihood of developing eating disorders compared to either mood or anxiety disorders alone. Similar risks and trends were evident in within-family-analyses of twin pairs discordant for baseline predictors and eating disorder outcome. Conclusions Depressive and generalized anxiety disorders manifest at age 14 predict future eating disorders. Analysis of discordant twins suggested that early-onset depressive and generalized anxiety disorders prospectively relate to eating disorders in adolescence, even after familial factors are taken into account. PMID:19059509

  11. Linkage of early-onset osteoarthritis and chondrocalcinosis to human chromosome 8q

    SciTech Connect

    Baldwin, C.T.; Farrer, L.A.; Adair, R. [Boston Univ. School of Medicine, MA (United States); Dharmavaram, R.; Jimenez, S. [Thomas Jefferson Univ., Philadelphia, PA (United States); Anderson, L. [Rheumatology Associates, Portland, ME (United States)

    1995-03-01

    Calcium pyrophosphate-deposition disease (CPDD), also called {open_quotes}chondrocalcinosis{close_quotes} or {open_quotes}pseudogout{close_quotes}, is a disorder characterized by the deposition of calcium-containing crystals in joint tissue, which leads to arthritis-like symptoms. The presence of these crystals in joint tissue is a common finding in the elderly, and, in this population, there is a poor correlation with joint pain. In contrast, early-onset CPDD has been described in several large families in which the disease progresses to severe degenerative osteoarthritis (OA). In these families, an autosomal dominant mode of inheritance is observed, with an age at onset between the 2nd and 5th decades of life. In this report, we describe a large New England family with early-onset CPDD and severe degenerative OA. We found genetic linkage between the disease in this family and chromosome 8q, with a multipoint lod score of 4.06. These results suggest that a defective gene at this location causes the disease in this family. 29 refs., 2 figs., 1 tab.

  12. Familial risk of early and late onset cancer: nationwide prospective cohort study

    PubMed Central

    2012-01-01

    Objective To determine whether familial risk of cancer is limited to early onset cases. Design Nationwide prospective cohort study. Setting Nationwide Swedish Family-Cancer Database. Participants All Swedes born after 1931 and their biological parents, totalling >12.2 million individuals, including >1.1 million cases of first primary cancer. Main outcome measures Familial risks of the concordant cancers by age at diagnosis. Results The highest familial risk was seen for offspring whose parents were diagnosed at an early age. Familial risks were significantly increased for colorectal, lung, breast, prostate, and urinary bladder cancer and melanoma, skin squamous cell carcinoma, and non-Hodgkin’s lymphoma, even when parents were diagnosed at age 70-79 or 80-89. When parents were diagnosed at more advanced ages (?90), the risk of concordant cancer in offspring was still significantly increased for skin squamous cell carcinoma (hazard ratio 1.9, 95% confidence interval 1.4 to 2.7), colorectal (1.6, 1.2 to 2.0), breast (1.3, 1.0 to 1.6), and prostate cancer (1.3, 1.1 to 1.6). For offspring with a cancer diagnosed at ages 60-76 whose parents were affected at age <50, familial risks were not significantly increased for nearly all cancers. Conclusion Though the highest familial risks of cancer are seen in offspring whose parents received a diagnosis of a concordant cancer at earlier ages, increased risks exist even in cancers of advanced ages. Familial cancers might not be early onset in people whose family members were affected at older ages and so familial cancers might have distinct early and late onset components. PMID:23257063

  13. Fluorodeoxyglucose-Positron Emission Tomography in the differential diagnosis of early-onset dementia: a prospective, community-based study

    Microsoft Academic Search

    Peter K Panegyres; Jeffrey M Rogers; Michael McCarthy; Andrew Campbell; Jing Shan Wu

    2009-01-01

    BACKGROUND: The aim of this study was to evaluate the diagnostic accuracy of positron emission tomography (PET) using F18 fluorodeoxyglucose (FDG) in the differential diagnosis of early-onset Alzheimer's disease (AD) and other dementias in a community-dwelling population. METHODS: A prospective sample of 102 individuals presenting consecutively to a primary care centre for examination of suspected early-onset dementing diseases. The mean

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

    PubMed

    Tan, Dandan; Yang, Haipo; Yuan, Yun; Bonnemann, Carsten; Chang, Xingzhi; Wang, Shuang; Wu, Yuchen; Wu, Xiru; Xiong, Hui

    2015-01-01

    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. PMID:26098624

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

    PubMed Central

    Tan, Dandan; Yang, Haipo; Yuan, Yun; Bonnemann, Carsten; Chang, Xingzhi; Wang, Shuang; Wu, Yuchen; Wu, Xiru; Xiong, Hui

    2015-01-01

    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. PMID:26098624

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

    PubMed

    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. PMID:25296563

  17. The natural history of early-onset dementia: the Artemis Project

    PubMed Central

    Atkins, Emily R; Bulsara, Max K; Panegyres, Peter K

    2012-01-01

    Objectives The natural history of early-onset Alzheimer's disease (AD) and fronto-temporal dementia (FTD) remains to be described in detail. We seek to describe the natural history of early onset AD and FTD in terms of changes in cognitive assessment and staging, medical history and survival. Design Longitudinal prospective cohort analysis. Setting Neurodegenerative disorders research clinic. Participants In total, 155 consecutive patients with clinically confirmed sporadic early-onset AD or FTD at a neurodegenerative disorders research clinic in Subiaco, Western Australia (The Artemis Project). Methods A detailed history was recorded from the patients at baseline, including education, family history and medical history. Mini-mental state exam (MMSE), Global Deterioration Scale (GDS) and total functional capacity (TFC) were determined at each visit from 1994 until 2011. Kaplan-Meier survival analysis was performed. Results Patients with FTD were more likely to have a family history of dementia (p=0.026), to develop at least one cerebrovascular risk factor (p=0.003), manifest depression (Fisher's exact p=0.007) and to die during the follow-up period (Pearson ?2 8.97, p=0.003). Kaplan-Meier survival estimates revealed a highly significant difference in the proportion of patients surviving the follow-up period (log rank 7.25, p=0.007) with FTD patients experiencing poorer survival than those with AD. The mean MMSE and TFC were consistently lower in those with FTD compared with those with AD over a decade of follow-up; mean GDS was consistently higher in those with FTD over the follow-up period. Conclusions We believe that the difference in survival in patients with AD and FTD in our cohort might relate to the development of one or more cerebrovascular risk factors in FTD patients and the severity of the underlying pathology. PMID:23059847

  18. Early-onset Formation of Parenchymal Plaque Amyloid Abrogates Cerebral Microvascular Amyloid Accumulation in Transgenic Mice*

    PubMed Central

    Xu, Feng; Kotarba, AnnMarie E.; Ou-Yang, Ming-Hsuan; Fu, Ziao; Davis, Judianne; Smith, Steven O.; Van Nostrand, William E.

    2014-01-01

    The fibrillar assembly and deposition of amyloid ? (A?) protein, a key pathology of Alzheimer disease, can occur in the form of parenchymal amyloid plaques and cerebral amyloid angiopathy (CAA). Familial forms of CAA exist in the absence of appreciable parenchymal amyloid pathology. The molecular interplay between parenchymal amyloid plaques and CAA is unclear. Here we investigated how early-onset parenchymal amyloid plaques impact the development of microvascular amyloid in transgenic mice. Tg-5xFAD mice, which produce non-mutated human A? and develop early-onset parenchymal amyloid plaques, were bred to Tg-SwDI mice, which produce familial CAA mutant human A? and develop cerebral microvascular amyloid. The bigenic mice presented with an elevated accumulation of A? and fibrillar amyloid in the brain compared with either single transgenic line. Tg-SwDI/Tg-5xFAD mice were devoid of microvascular amyloid, the prominent pathology of Tg-SwDI mice, but exhibited larger parenchymal amyloid plaques compared with Tg-5xFAD mice. The larger parenchymal amyloid deposits were associated with a higher loss of cortical neurons and elevated activated microglia in the bigenic Tg-SwDI/Tg-5xFAD mice. The periphery of parenchymal amyloid plaques was largely composed of CAA mutant A?. Non-mutated A? fibril seeds promoted CAA mutant A? fibril formation in vitro. Further, intrahippocampal administration of biotin-labeled CAA mutant A? peptide accumulated on and adjacent to pre-existing parenchymal amyloid plaques in Tg-5xFAD mice. These findings indicate that early-onset parenchymal amyloid plaques can serve as a scaffold to capture CAA mutant A? peptides and prevent their accumulation in cerebral microvessels. PMID:24828504

  19. Association Between Early-Onset Parkinson Disease and 22q11.2 Deletion Syndrome

    PubMed Central

    Butcher, Nancy J.; Kiehl, Tim-Rasmus; Hazrati, Lili-Naz; Chow, Eva W. C.; Rogaeva, Ekaterina; Lang, Anthony E.; Bassett, Anne S.

    2015-01-01

    IMPORTANCE Clinical case reports of parkinsonism co-occurring with hemizygous 22q11.2 deletions and the associated multisystem syndrome, 22q11.2 deletion syndrome (22q11.2DS), suggest that 22q11.2 deletions may lead to increased risk of early-onset Parkinson disease (PD). The frequency of PD and its neuropathological presentation remain unknown in this common genetic condition. OBJECTIVE To evaluate a possible association between 22q11.2 deletions and PD. DESIGN, SETTING, AND PARTICIPANTS An observational study of the occurrence of PD in the world’s largest cohort of well-characterized adults with a molecularly confirmed diagnosis of 22q11.2DS (n = 159 [6 with postmortem tissue]; age range, 18.1–68.6 years) was conducted in Toronto, Ontario, Canada. Rare postmortem brain tissue from individuals with 22q11.2DS and a clinical history of PD was investigated for neurodegenerative changes and compared with that from individuals with no history of a movement disorder. MAIN OUTCOMES AND MEASURES A clinical diagnosis of PD made by a neurologist and neuropathological features of PD. RESULTS Adults with 22q11.2DS had a significantly elevated occurrence of PD compared with standard population estimates (standardized morbidity ratio = 69.7; 95% CI, 19.0–178.5). All cases showed early onset and typical PD symptom pattern, treatment response, and course. All were negative for family history of PD and known pathogenic PD-related mutations. The common use of antipsychotics in patients with 22q11.2DS to manage associated psychiatric symptoms delayed diagnosis of PD by up to 10 years. Postmortem brain tissue revealed classic loss of midbrain dopaminergic neurons in all 3 postmortem 22q11.2DS-PD cases. Typical ?-synuclein–positive Lewy bodies were present in the expected distribution in 2 cases but absent in another. CONCLUSIONS AND RELEVANCE These findings suggest that 22q11.2 deletions represent a novel genetic risk factor for early-onset PD with variable neuropathological presentation reminiscent of LRRK2-associated PD neuropathology. Individuals with early-onset PD and classic features of 22q11.2DS should be considered for genetic testing, and those with a known 22q11.2 deletion should be monitored for the development of parkinsonian symptoms. Molecular studies of the implicated genes, including DGCR8, may help shed light on the underlying pathophysiology of PD in 22q11.2DS and idiopathic PD. PMID:24018986

  20. Electroretinographic findings in the Standard Wire Haired Dachshund with inherited early onset cone–rod dystrophy

    Microsoft Academic Search

    Ernst O. Ropstad; Ellen Bjerkås; Kristina Narfström

    2007-01-01

    Purpose  To describe electroretinographic (ERG) findings in a strain of Standard Wire Haired Dachshund (SWHD)-derived dogs at the ages\\u000a of approximately 5, 8 and 52 weeks selected for inherited early onset cone–rod dystrophy.\\u000a \\u000a \\u000a \\u000a Methods  Nineteen affected and 13 age-matched control SWHDs were included in the study. All dogs were subjected to standardized bilateral\\u000a Ganzfeld ERGs and ophthalmoscopic examinations at regular intervals.\\u000a \\u000a \\u000a \\u000a Results  Photopic cone-derived

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

    PubMed Central

    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

  2. General maturational lag as an essential correlate of early-onset psychosis.

    PubMed

    James, A L; Barry, R J

    1981-09-01

    Evidence for the increasing recognition of maturational lag in addition to intellectual impairment, associated with the syndrome of early-onset psychosis, is presented to indicate that developmental variables play a central role in the behavioral profile of autistic children. The failure of research to give methodological consideration to control of these variables is discussed, and implications for the interpretation of results from experimental studies are outlined. It is suggested that the distinction between controlling not only for mental age but also for chronological age to facilitate the delineation of specific deficits in this syndrome. PMID:6763611

  3. Very Early Onset Trichotillomania Presenting with Recurrent Trichobezoar: Conventional Wisdom Questioned

    PubMed Central

    Menon, Vikas; Shaik, Subahani; Mohan, Pazhanivel

    2015-01-01

    Trichotillomania (TTM), a disorder characterized by compulsive hair pulling, is undergoing a conceptual and nosological re-evaluation. Little long-term information is available about this condition when it strikes in early childhood. Trichobezoar, an ingestional foreign body lodged in the gastrointestinal tract composed of swallowed hair, is usually associated with underlying psychiatric and emotional disturbances. In this report, we describe a young girl who had her symptom onset at the age of 3, but presented again after more than a decade with recurrent symptomatic large trichobezoars needing surgical removal both times. Her clinical course and presentation challenged contemporary understanding of TTM. PMID:25878449

  4. Very early onset trichotillomania presenting with recurrent trichobezoar: conventional wisdom questioned.

    PubMed

    Menon, Vikas; Shaik, Subahani; Mohan, Pazhanivel

    2015-01-01

    Trichotillomania (TTM), a disorder characterized by compulsive hair pulling, is undergoing a conceptual and nosological re-evaluation. Little long-term information is available about this condition when it strikes in early childhood. Trichobezoar, an ingestional foreign body lodged in the gastrointestinal tract composed of swallowed hair, is usually associated with underlying psychiatric and emotional disturbances. In this report, we describe a young girl who had her symptom onset at the age of 3, but presented again after more than a decade with recurrent symptomatic large trichobezoars needing surgical removal both times. Her clinical course and presentation challenged contemporary understanding of TTM. PMID:25878449

  5. Empirical evidence for psychopharmacologic treatment in early-onset psychosis and schizophrenia.

    PubMed

    Maloney, Ann E; Yakutis, Lauren J; Frazier, Jean A

    2012-10-01

    Psychotic symptoms presenting in youth can be clinically complex and require that a child and adolescent psychiatrist use significant skill in making a diagnosis and initiating treatment. There are a number of illnesses to rule out before making a diagnosis of early-onset schizophrenia in particular. Psychosis in youth has significant associated morbidity and places high demands not only on families but also on the medical and educational systems. More effective pharmacologic and nonpharmacologic treatments for psychosis are needed. Nonpharmacologic therapies targeting relatively treatment-resistant domains of dysfunction such as neurocognition are also necessary as adjunctive treatments to our extant pharmacologic agents. PMID:23040906

  6. Commonly Used Periodontal Terms

    MedlinePLUS

    ... Also referred to as supportive periodontal therapy. necrotizing periodontal diseases An infection characterized by necrosis of gingival tissues, ... the bone. Usually destroyed by advanced cases of periodontal disease, creating increased mobility of the teeth. periodontal pocket ...

  7. Sunbed use during adolescence and early adulthood is associated with increased risk of early-onset melanoma

    PubMed Central

    Cust, Anne E; Armstrong, Bruce K; Goumas, Chris; Jenkins, Mark A; Schmid, Helen; Hopper, John L; Kefford, Richard F; Giles, Graham G; Aitken, Joanne F; Mann, Graham J

    2010-01-01

    Sunbed use is associated with increased risk of melanoma. Younger people might be more susceptible to the carcinogenic effects of ultraviolet radiation. We investigated the association between sunbed use and risk of early-onset cutaneous malignant melanoma. From the Australian Melanoma Family Study, a multi-centre, population-based, case-control-family study, we analysed data for 604 cases diagnosed between ages 18 and 39 years and 479 controls. Data were collected by interview. Associations were estimated as odds ratios (ORs) using unconditional logistic regression, adjusting for age, sex, city, education, family history, skin colour, usual skin response to sunlight, and sun exposure. Compared with having never used a sunbed, the OR for melanoma associated with ever-use was 1.41 (95% confidence interval (CI) 1.01-1.96), and 2.01 (95% CI 1.22-3.31) for more than 10 lifetime sessions (Ptrend 0.01 with cumulative use). The association was stronger for earlier age at first use (Ptrend 0.02). The association was also stronger for melanoma diagnosed when aged 18-29 years (OR for more than 10 lifetime sessions = 6.57, 95% CI 1.41-30.49) than for melanoma diagnosed when 30-39 years (OR 1.60, 95% CI 0.92-2.77; Pinteraction 0.01). Among those who had ever used a sunbed and were diagnosed between 18-29 years of age, three quarters (76%) of melanomas were attributable to sunbed use. Sunbed use is associated with increased risk of early-onset melanoma, with risk increasing with greater use, an earlier age at first use and for earlier onset disease. PMID:20669232

  8. The street children of Manila are affected by early-in-life periodontal infection: description of a treatment modality: sea salt.

    PubMed

    Michel, J F; Michel, M G; Nadan, J; Nowzari, H

    2013-01-01

    Thousands of street children of Manila are affected by early-in-life oral infection. The aim of the present investigation was to evaluate the effectiveness of a sea-salt mouthrinse solution in street children of Manila affected by mild to severe forms of periodontal disease. These children were all in need of special protection: abandoned, abused, exploited, neglected, orphaned, poor. During 3 oral-health missions in 2003, 2004 and 2005, 617 abandoned children (5 to 13 year-old), received oral examination at a non-sectarian child-caring institution in Metro Manila (Virlanie Foundation) by calibrated examiners. A treatment based on what could be done was proposed: 1. Teaching of a precise tooth brushing technique with sea-salt, controlled and reinforced every two days for one week by calibrated health educators, 2. The application of sea-salt water mouthrinse (2.5 gram in 20 ml). Periodontal measurements were repeated at the end of each mission. All children returned to child-caring institution for the followup examinations. In 2003, 10 male and 11 female (n=21) were diagnosed with aggressive periodontitis. In 2009 and 2010, none was affected by aggressive periodontitis. For all patients, the gingival index decreased from 1.08 at the first mission to 1.04 at the end of the second mission and 0.98 at the end of the third mission. The periodontal index decreased from 1.33 at the first mission to 0.98 at the second mission and 0.92 at the last mission. The present investigation confirms that prevention and early diagnosis can result in success with minimum cost. The provided oral health program empowered street children in the most desperate circumstances to be educated and become self-reliant, independent, and responsible. We propose here an antimicrobial approach which has a high degree of efficacy and tolerability, and can be implemented in virtually all parts of the world using low-cost resources. PMID:23697295

  9. [Anti-NMDA-receptor encephalitis: a new axis-III disorder in the differential diagnosis of childhood disintegrative disorder, early onset schizophrenia and late onset autism].

    PubMed

    Creten, C; van der Zwaan, S; Blankespoor, R J; Maatkamp, A; Klinkenberg, S; van Kranen-Mastenbroek, V H J M; Nicolai, J; Dhossche, D M; van Os, J; Schieveld, J N M

    2012-01-01

    Childhood disintegrative disorder (CDD), early onset schizophrenia (EOS), and late onset autism (LOA) often follow a similar course: initially, development is normal, then there is a sudden neuropsychiatric deterioration of social interaction and communication skills, which is combined with a decline in intelligence and reduction in daily activities. A 9-year-old boy was admitted to the paediatric ward with acute onset of secondary epileptic seizures. It was not long until the boy's symptoms resembled that of patients with cdd, eos and loa. Intensive tests led to the diagnosis of anti-NMDA-receptor encephalitis. Anti-NMDA-receptor encephalitis should be regarded as a possible organic cause underlying the syndromal presentation of CDD, EOS and LOA. PMID:22588963

  10. Early microbial and metabolomic signatures predict later onset of necrotizing enterocolitis in preterm infants

    PubMed Central

    2013-01-01

    Background Necrotizing enterocolitis (NEC) is a devastating intestinal disease that afflicts 10% of extremely preterm infants. The contribution of early intestinal colonization to NEC onset is not understood, and predictive biomarkers to guide prevention are lacking. We analyzed banked stool and urine samples collected prior to disease onset from infants <29 weeks gestational age, including 11 infants who developed NEC and 21 matched controls who survived free of NEC. Stool bacterial communities were profiled by 16S rRNA gene sequencing. Urinary metabolomic profiles were assessed by NMR. Results During postnatal days 4 to 9, samples from infants who later developed NEC tended towards lower alpha diversity (Chao1 index, P = 0.086) and lacked Propionibacterium (P = 0.009) compared to controls. Furthermore, NEC was preceded by distinct forms of dysbiosis. During days 4 to 9, samples from four NEC cases were dominated by members of the Firmicutes (median relative abundance >99% versus <17% in the remaining NEC and controls, P < 0.001). During postnatal days 10 to 16, samples from the remaining NEC cases were dominated by Proteobacteria, specifically Enterobacteriaceae (median relative abundance >99% versus 38% in the other NEC cases and 84% in controls, P = 0.01). NEC preceded by Firmicutes dysbiosis occurred earlier (onset, days 7 to 21) than NEC preceded by Proteobacteria dysbiosis (onset, days 19 to 39). All NEC cases lacked Propionibacterium and were preceded by either Firmicutes (?98% relative abundance, days 4 to 9) or Proteobacteria (?90% relative abundance, days 10 to 16) dysbiosis, while only 25% of controls had this phenotype (predictive value 88%, P = 0.001). Analysis of days 4 to 9 urine samples found no metabolites associated with all NEC cases, but alanine was positively associated with NEC cases that were preceded by Firmicutes dysbiosis (P < 0.001) and histidine was inversely associated with NEC cases preceded by Proteobacteria dysbiosis (P = 0.013). A high urinary alanine:histidine ratio was associated with microbial characteristics (P < 0.001) and provided good prediction of overall NEC (predictive value 78%, P = 0.007). Conclusions Early dysbiosis is strongly involved in the pathobiology of NEC. These striking findings require validation in larger studies but indicate that early microbial and metabolomic signatures may provide highly predictive biomarkers of NEC. PMID:24450576

  11. Germline Mutations of Inhibins in Early-Onset Ovarian Epithelial Tumors

    PubMed Central

    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 ?A-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 ?-subunit, the partner of the ?A-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

  12. Structured Regions of Alpha-synuclein Fibrils Include the Early Onset Parkinson's Disease Mutation Sites

    SciTech Connect

    Comellas Canal, Gemma; Lemkau, Luisel R.; Nieuwkoop, Andrew J.; Kloepper, Kathryn D.; Ladror, Daniel T.; Ebisu, Reika; Woods, Wendy S.; Lipton, Andrew S.; George, Julia M.; Rienstra, Chad M.

    2011-08-26

    Alpha-Synuclein (AS) fibrils constitute the major proteinaceous component of Lewy bodies (LBs), the pathological hallmark of Parkinson’s disease (PD) and other neurodegenerative diseases. Three single point mutations in the AS gene, as well as multiplication of the wild-type (WT) AS allele, have been previously identified in families with early-onset PD. Although AS fibrils have been the subject of intense study, critical details about their structure including the precise location of the B-strands and the extent of the core, the three-dimensional structure and the effects of the mutations—remain unknown. Here, we have used magic-angle spinning solid-state NMR spectroscopy to present a detailed characterization of the full-length WT AS fibrils. With improved sample preparations, isotopic labeling patterns and NMR experiments, we have confidently assigned more than 90% of the 13C and 15N backbone and sidechain chemical shifts of the detected residues from residue 39 to 97, and quantified the conformational dynamics throughout this region. Our results demonstrate that the core of AS fibrils extends with a repeated motif and that residues 30, 46 and 53-the early-onset PD mutant sites-are located in structured regions of AS fibrils.

  13. Mutations in FBXL4, encoding a mitochondrial protein, cause early-onset mitochondrial encephalomyopathy.

    PubMed

    Gai, Xiaowu; Ghezzi, Daniele; Johnson, Mark A; Biagosch, Caroline A; Shamseldin, Hanan E; Haack, Tobias B; Reyes, Aurelio; Tsukikawa, Mai; Sheldon, Claire A; Srinivasan, Satish; Gorza, Matteo; Kremer, Laura S; Wieland, Thomas; Strom, Tim M; Polyak, Erzsebet; Place, Emily; Consugar, Mark; Ostrovsky, Julian; Vidoni, Sara; Robinson, Alan J; Wong, Lee-Jun; Sondheimer, Neal; Salih, Mustafa A; Al-Jishi, Emtethal; Raab, Christopher P; Bean, Charles; Furlan, Francesca; Parini, Rossella; Lamperti, Costanza; Mayr, Johannes A; Konstantopoulou, Vassiliki; Huemer, Martina; Pierce, Eric A; Meitinger, Thomas; Freisinger, Peter; Sperl, Wolfgang; Prokisch, Holger; Alkuraya, Fowzan S; Falk, Marni J; Zeviani, Massimo

    2013-09-01

    Whole-exome sequencing and autozygosity mapping studies, independently performed in subjects with defective combined mitochondrial OXPHOS-enzyme deficiencies, identified a total of nine disease-segregating FBXL4 mutations in seven unrelated mitochondrial disease families, composed of six singletons and three siblings. All subjects manifested early-onset lactic acidemia, hypotonia, and developmental delay caused by severe encephalomyopathy consistently associated with progressive cerebral atrophy and variable involvement of the white matter, deep gray nuclei, and brainstem structures. A wide range of other multisystem features were variably seen, including dysmorphism, skeletal abnormalities, poor growth, gastrointestinal dysmotility, renal tubular acidosis, seizures, and episodic metabolic failure. Mitochondrial respiratory chain deficiency was present in muscle or fibroblasts of all tested individuals, together with markedly reduced oxygen consumption rate and hyperfragmentation of the mitochondrial network in cultured cells. In muscle and fibroblasts from several subjects, substantially decreased mtDNA content was observed. FBXL4 is a member of the F-box family of proteins, some of which are involved in phosphorylation-dependent ubiquitination and/or G protein receptor coupling. We also demonstrate that FBXL4 is targeted to mitochondria and localizes in the intermembrane space, where it participates in an approximately 400 kDa protein complex. These data strongly support a role for FBXL4 in controlling bioenergetic homeostasis and mtDNA maintenance. FBXL4 mutations are a recurrent cause of mitochondrial encephalomyopathy onset in early infancy. PMID:23993194

  14. Onset-related differences in neural substrates of tinnitus-related distress: the anterior cingulate cortex in late-onset tinnitus, and the frontal cortex in early-onset tinnitus.

    PubMed

    Song, Jae-Jin; Vanneste, Sven; Schlee, Winfried; Van de Heyning, Paul; De Ridder, Dirk

    2015-01-01

    Recent findings regarding differences in tinnitus-related neural activity according to onset age have raised a question on possible onset age-related differences in neural substrates of distress. Hence we collected quantitative electroencephalography (qEEG) findings of 28 late-onset tinnitus (LOT) and 29 early-onset tinnitus (EOT) (mean onset age 52.3 and 29.0 years, respectively) participants. According to the tinnitus questionnaire (TQ) score grade, LOTs were then subdivided into 13 high distress (HD; TQ grade 3 or 4) and 15 low distress (LD; TQ grade 1 or 2), while EOTs into 14 HD and 15 LD. Compared to the EOT group, the LOT group demonstrated increased qEEG source-localized activity and functional connectivity primarily in the anterior cingulate cortex (ACC) and parahippocampus. In subgroup comparisons, the ACC was activated more in HD-LOT participants than in LD-LOT participants for the beta 1, beta 2 and gamma frequency bands, while the left orbitofrontal cortex and left dorsolateral prefrontal cortex were activated more in HD-EOT than in LD-EOT for the delta/beta and gamma frequency bands, respectively. Even with the same amount of tinnitus-related distress level, responsible neural substrates are different according to the onset age. These differences may be important for exploring different target areas of treatment according to tinnitus onset age, as well as for conducting similar studies on other pathologies, such as depression or pain. PMID:24135769

  15. Early-Onset Basal Cell Carcinoma and Indoor Tanning: A Population-Based Study

    PubMed Central

    Zens, M. Scot; Li, Zhigang; Stukel, Therese A.; Perry, Ann E.; Gilbert-Diamond, Diane; Sayarath, Vicki; Stephenson, Rita S.; Barton, Dorothea; Nelson, Heather H.; Spencer, Steven K.

    2014-01-01

    OBJECTIVE: Indoor tanning with UV radiation–emitting lamps is common among adolescents and young adults. Rising incidence rates of basal cell carcinoma (BCC) have been reported for the United States and elsewhere, particularly among those diagnosed at younger ages. Recent epidemiologic studies have raised concerns that indoor tanning may be contributing to early occurrence of BCC, and younger people may be especially vulnerable to cancer risk associated with this exposure. Therefore, we sought to address these issues in a population-based case–control study from New Hampshire. METHODS: Data on indoor tanning were obtained on 657 cases of BCC and 452 controls ?50 years of age. RESULTS: Early-onset BCC was related to indoor tanning, with an adjusted odds ratio (OR) of 1.6 (95% confidence interval, 1.3–2.1). The strongest association was observed for first exposure as an adolescent or young adult, with a 10% increase in the OR with each age younger at first exposure (OR per year of age ?23 = 1.1; 95% confidence interval, 1.0–1.2). Associations were present for each type of device examined (ie, sunlamps, tanning beds, and tanning booths). CONCLUSIONS: Our findings suggest early exposure to indoor tanning increases the risk of early development of BCC. They also underscore the importance of counseling adolescents and young adults about the risks of indoor tanning and for discouraging parents from consenting minors to this practice. PMID:24958589

  16. Plant macrofossil evidence for an early onset of the Holocene summer thermal maximum in northernmost Europe

    PubMed Central

    Väliranta, M.; Salonen, J. S.; Heikkilä, M.; Amon, L.; Helmens, K.; Klimaschewski, A.; Kuhry, P.; Kultti, S.; Poska, A.; Shala, S.; Veski, S.; Birks, H. H.

    2015-01-01

    Holocene summer temperature reconstructions from northern Europe based on sedimentary pollen records suggest an onset of peak summer warmth around 9,000 years ago. However, pollen-based temperature reconstructions are largely driven by changes in the proportions of tree taxa, and thus the early-Holocene warming signal may be delayed due to the geographical disequilibrium between climate and tree populations. Here we show that quantitative summer-temperature estimates in northern Europe based on macrofossils of aquatic plants are in many cases ca. 2?°C warmer in the early Holocene (11,700–7,500 years ago) than reconstructions based on pollen data. When the lag in potential tree establishment becomes imperceptible in the mid-Holocene (7,500 years ago), the reconstructed temperatures converge at all study sites. We demonstrate that aquatic plant macrofossil records can provide additional and informative insights into early-Holocene temperature evolution in northernmost Europe and suggest further validation of early post-glacial climate development based on multi-proxy data syntheses. PMID:25858780

  17. Inherited DOCK2 Deficiency in Patients with Early-Onset Invasive Infections.

    PubMed

    Dobbs, Kerry; Domínguez Conde, Cecilia; Zhang, Shen-Ying; Parolini, Silvia; Audry, Magali; Chou, Janet; Haapaniemi, Emma; Keles, Sevgi; Bilic, Ivan; Okada, Satoshi; Massaad, Michel J; Rounioja, Samuli; Alwahadneh, Adel M; Serwas, Nina K; Capuder, Kelly; Çiftçi, Ergin; Felgentreff, Kerstin; Ohsumi, Toshiro K; Pedergnana, Vincent; Boisson, Bertrand; Haskolo?lu, ?ule; Ensari, Arzu; Schuster, Michael; Moretta, Alessandro; Itan, Yuval; Patrizi, Ornella; Rozenberg, Flore; Lebon, Pierre; Saarela, Janna; Knip, Mikael; Petrovski, Slavé; Goldstein, David B; Parrott, Roberta E; Savas, Berna; Schambach, Axel; Tabellini, Giovanna; Bock, Christoph; Chatila, Talal A; Comeau, Anne Marie; Geha, Raif S; Abel, Laurent; Buckley, Rebecca H; ?kincio?ullar?, Aydan; Al-Herz, Waleed; Helminen, Merja; Do?u, Figen; Casanova, Jean-Laurent; Boztu?, Kaan; Notarangelo, Luigi D

    2015-06-18

    Background Combined immunodeficiencies are marked by inborn errors of T-cell immunity in which the T cells that are present are quantitatively or functionally deficient. Impaired humoral immunity is also common. Patients have severe infections, autoimmunity, or both. The specific molecular, cellular, and clinical features of many types of combined immunodeficiencies remain unknown. Methods We performed genetic and cellular immunologic studies involving five unrelated children with early-onset invasive bacterial and viral infections, lymphopenia, and defective T-cell, B-cell, and natural killer (NK)-cell responses. Two patients died early in childhood; after allogeneic hematopoietic stem-cell transplantation, the other three had normalization of T-cell function and clinical improvement. Results We identified biallelic mutations in the dedicator of cytokinesis 2 gene (DOCK2) in these five patients. RAC1 activation was impaired in the T cells. Chemokine-induced migration and actin polymerization were defective in the T cells, B cells, and NK cells. NK-cell degranulation was also affected. Interferon-? and interferon-? production by peripheral-blood mononuclear cells was diminished after viral infection. Moreover, in DOCK2-deficient fibroblasts, viral replication was increased and virus-induced cell death was enhanced; these conditions were normalized by treatment with interferon alfa-2b or after expression of wild-type DOCK2. Conclusions Autosomal recessive DOCK2 deficiency is a new mendelian disorder with pleiotropic defects of hematopoietic and nonhematopoietic immunity. Children with clinical features of combined immunodeficiencies, especially with early-onset, invasive infections, may have this condition. (Supported by the National Institutes of Health and others.). PMID:26083206

  18. Early-Onset Stroke and Vasculopathy Associated with Mutations in ADA2

    PubMed Central

    Zhou, Q.; Yang, D.; Ombrello, A.K.; Zavialov, Andrey V.; Toro, C.; Zavialov, Anton V.; Stone, D.L.; Chae, J.J.; Rosenzweig, S.D.; Bishop, K.; Barron, K.S.; Kuehn, H.S.; Hoffmann, P.; Negro, A.; Tsai, W.L.; Cowen, E.W.; Pei, W.; Milner, J.D.; Silvin, C.; Heller, T.; Chin, D.T.; Patronas, N.J.; Barber, J.S.; Lee, C.-C.R.; Wood, G.M.; Ling, A.; Kelly, S.J.; Kleiner, D.E.; Mullikin, J.C.; Ganson, N.J.; Kong, H.H.; Hambleton, S.; Candotti, F.; Quezado, M.M.; Calvo, K.R.; Alao, H.; Barham, B.K.; Jones, A.; Meschia, J.F.; Worrall, B.B.; Kasner, S.E.; Rich, S.S.; Goldbach-Mansky, R.; Abinun, M.; Chalom, E.; Gotte, A.C.; Punaro, M.; Pascual, V.; Verbsky, J.W.; Torgerson, T.R.; Singer, N.G.; Gershon, T.R.; Ozen, S.; Karadag, O.; Fleisher, T.A.; Remmers, E.F.; Burgess, S.M.; Moir, S.L.; Gadina, M.; Sood, R.; Hershfield, M.S.; Boehm, M.; Kastner, D.L.; Aksentijevich, I.

    2014-01-01

    BACKGROUND We observed a syndrome of intermittent fevers, early-onset lacunar strokes and other neurovascular manifestations, livedoid rash, hepatosplenomegaly, and systemic vasculopathy in three unrelated patients. We suspected a genetic cause because the disorder presented in early childhood. METHODS We performed whole-exome sequencing in the initial three patients and their unaffected parents and candidate-gene sequencing in three patients with a similar phenotype, as well as two young siblings with polyarteritis nodosa and one patient with small-vessel vasculitis. Enzyme assays, immunoblotting, immunohistochemical testing, flow cytometry, and cytokine profiling were performed on samples from the patients. To study protein function, we used morpholino-mediated knockdowns in zebrafish and short hairpin RNA knockdowns in U937 cells cultured with human dermal endothelial cells. RESULTS All nine patients carried recessively inherited mutations in CECR1 (cat eye syndrome chromosome region, candidate 1), encoding adenosine deaminase 2 (ADA2), that were predicted to be deleterious; these mutations were rare or absent in healthy controls. Six patients were compound heterozygous for eight CECR1 mutations, whereas the three patients with polyarteritis nodosa or small-vessel vasculitis were homozygous for the p.Gly47Arg mutation. Patients had a marked reduction in the levels of ADA2 and ADA2-specific enzyme activity in the blood. Skin, liver, and brain biopsies revealed vasculopathic changes characterized by compromised endothelial integrity, endothelial cellular activation, and inflammation. Knockdown of a zebrafish ADA2 homologue caused intracranial hemorrhages and neutropenia — phenotypes that were prevented by coinjection with nonmutated (but not with mutated) human CECR1. Monocytes from patients induced damage in cocultured endothelial-cell layers. CONCLUSIONS Loss-of-function mutations in CECR1 were associated with a spectrum of vascular and inflammatory phenotypes, ranging from early-onset recurrent stroke to systemic vasculopathy or vasculitis. (Funded by the National Institutes of Health Intramural Research Programs and others.) PMID:24552284

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

    PubMed Central

    Yoshihara, Yujiro; Sugihara, Genichi; Matsumoto, Hideo; Suckling, John; Nishimura, Katsuhiko; Toyoda, Takao; Isoda, Haruo; Tsuchiya, Kenji J; Takebayashi, Kiyokazu; Suzuki, Katsuaki; Sakahara, Harumi; Nakamura, Kazuhiko; Mori, Norio; Takei, Nori

    2008-01-01

    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 and the symptom severity. These findings suggest that at an early stage of the illness, especially for those with onset before brain maturation, a wide range of disturbed neural circuits, including these brain regions that show no apparent morphological changes, may contribute to the formation of the symptomatology. PMID:19102744

  20. Phenotype variability and early onset ataxia symptoms in spinocerebellar ataxia type 7: comparison and correlation with other spinocerebellar ataxias.

    PubMed

    de Albuquerque, Marcus Vinicius Cristino; Pedroso, José Luiz; Braga Neto, Pedro; Barsottini, Orlando Graziani Povoas

    2015-01-01

    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. PMID:25608122

  1. Early onset degenerative dementias: demographic characteristics and etiologic classification in a tertiary referral center.

    PubMed

    Maiovis, Pantelis; Ioannidis, Panagiotis; Konstantinopoulou, Elina; Karacostas, Dimitris

    2015-03-01

    Early onset dementia (EOD) is a major diagnostic challenge as it often presents with atypical features and may be attributed to treatable diseases. Primary degenerative dementias (Alzheimer's disease-AD, frontotemporal lobar degeneration-FTLD, Lewy body dementia-LBD), although traditionally considered to affect older people, are still a main cause of EOD. 491 demented patients were assessed from January 1, 2003 to December 31, 2010 in the Neurology Department of a tertiary referral center. Patients were classified as AD, behavioral variant frontotemporal dementia (bvFTD), non-fluent agrammatic variant primary progressive aphasia (naPPA), semantic variant PPA (svPPA), corticobasal degeneration (CBD), or progressive supranuclear palsy (PSP) who also met criteria for naPPA and LBD. Finally, their demographic characteristics were analysed, according to age at onset (EOD <65 years, late onset dementia-LOD ?65 years). From the 491 patients, 137 (27.9 %) were EOD. In the EOD group, 52 (38 %) were diagnosed with bvFTD, 34 (24.8 %) with AD, 27 (19.7 %) with naPPA, 10 (7.2 %) with svPPA, 12 (8.8 %) with CBD or PSP, and 2 (1.5 %) with LBD. Demographic characteristics did not differ significantly among diagnostic categories in the EOD group, while in the LOD group FTLD patients were younger and more frequently men compared to both AD and LBD patients. EOD patients had more years of education than LOD patients. Degenerative disorders as causes of EOD are not rare. High clinical alertness is warranted to achieve correct and timely diagnosis. PMID:24878660

  2. Defining Early-Onset Kidney Cancer: Implications for Germline and Somatic Mutation Testing and Clinical Management

    PubMed Central

    Shuch, Brian; Vourganti, Srinivas; Ricketts, Christopher J.; Middleton, Lindsay; Peterson, James; Merino, Maria J.; Metwalli, Adam R.; Srinivasan, Ramaprasad; Linehan, W. Marston

    2014-01-01

    Purpose Approximately 5% to 8% of renal cell carcinoma (RCC) is hereditary. No guidelines exist for patient selection for RCC germline mutation testing. We evaluate how age of onset could indicate the need for germline mutation testing for detection of inherited forms of kidney cancer. Patients and Methods We analyzed the age distribution of RCC cases in the SEER-17 program and in our institutional hereditary kidney cancer population. The age distributions were compared by sex, race, histology, and hereditary cancer syndrome. Models were established to evaluate the specific age thresholds for genetic testing. Results The median age of patients with RCC in SEER-17 was 64 years, with the distribution closely approaching normalcy. Statistical differences were observed by race, sex, and subtype (P < .05). The bottom decile cutoff was ? 46 years of age and slightly differed by sex, race, and histology. The mean and median ages at presentation of 608 patients with hereditary kidney cancer were 39.3 years and 37 years, respectively. Although age varied by specific syndrome, 70% of these cases were found to lie at or below the bottom age decile. Modeling age-based genetic testing thresholds demonstrated that the 10th percentile maximized sensitivity and specificity. Conclusion Early age of onset might be a sign of hereditary RCC. Even in the absence of clinical manifestations and personal/family history, an age of onset of 46 years or younger should trigger consideration for genetic counseling/germline mutation testing and may serve as a useful cutoff when establishing genetic testing guidelines. PMID:24378414

  3. Mapping Callosal Morphology in Early and Late-Onset Elderly Depression: An Index of Distinct Changes in Cortical Connectivity

    Microsoft Academic Search

    Martina Ballmaier; Anand Kumar; Virginia Elderkin-Thompson; Katherine L Narr; Eileen Luders; Paul M Thompson; Cornelius Hojatkashani; Daniel Pham; Andreas Heinz; Arthur W Toga

    2008-01-01

    There is some evidence of corpus callosum abnormalities in elderly depression, but it is not known whether these deficits are region-specific or differ based on age at onset of depression. Twenty-four patients with early-onset depression (mean age=68.00, SD±5.83), 22 patients with late-onset depression (mean age=74.50, SD±8.09) and 34 elderly control subjects (mean age=72.38; SD±6.93) were studied. Using 3D MRI data,

  4. Using bacterial biomarkers to identify early indicators of cystic fibrosis pulmonary exacerbation onset

    PubMed Central

    Rogers, Geraint B; Hoffman, Lucas R; Johnson, Matt W; Mayer-Hamblett, Nicole; Schwarze, Jürgen; Carroll, Mary P; Bruce, Kenneth D

    2011-01-01

    Acute periods of pulmonary exacerbation are the single most important cause of morbidity in cystic fibrosis patients, and may be associated with a loss of lung function. Intervening prior to the onset of a substantially increased inflammatory response may limit the associated damage to the airways. While a number of biomarker assays based on inflammatory markers have been developed, providing useful and important measures of disease during these periods, such factors are typically only elevated once the process of exacerbation has been initiated. Identifying biomarkers that can predict the onset of pulmonary exacerbation at an early stage would provide an opportunity to intervene before the establishment of a substantial immune response, with major implications for the advancement of cystic fibrosis care. The precise triggers of pulmonary exacerbation remain to be determined; however, the majority of models relate to the activity of microbes present in the patient's lower airways of cystic fibrosis. Advances in diagnostic microbiology now allow for the examination of these complex systems at a level likely to identify factors on which biomarker assays can be based. In this article, we discuss key considerations in the design and testing of assays that could predict pulmonary exacerbations. PMID:21405970

  5. Early-onset progressive osteoarthritis with hereditary progressive ophtalmopathy or Stickler syndrome.

    PubMed

    Couchouron, Tifenn; Masson, Charles

    2011-01-01

    Stickler syndrome is a group of rare genetic conditions (incidence, 1/7500 births) related to mutations in the collagen genes. Both the mutations and the clinical features vary widely across affected patients. The main manifestations are craniofacial birth defects, bone and joint symptoms, ocular abnormalities, and hearing loss. Stickler syndrome may be revealed at birth (25% of cases) by a combination of cleft palate, retrognathism, and micrognathism known as Pierre Robin sequence, which may cause neonatal respiratory problems. The ocular abnormalities include severe myopia, abnormalities of the vitreous, and a high risk of retinal detachment (60% of cases), which may cause blindness (4% of cases). Severe hearing loss with onset in early childhood may impair performance at school. Osteoarthritis (75% of patients) with onset before 30 years of age is a severe manifestation that causes chronic hip and low back pain and functional impairments. Joint replacement surgery is often required. The risk associated with multiple anesthesias is highest in patients with craniofacial defects. The bone status may deserve to be evaluated, as the combination of genetic abnormalities and physical impairments may promote bone loss. Clinicians should be cognizant of Stickler syndrome so that they can detect the disease in patients and their family members, prevent functional impairments, organize a multidisciplinary management strategy, and arrange for genetic counseling. PMID:20462780

  6. A qualitative interview study: patient accounts of medication use in early rheumatoid arthritis from symptom onset to early postdiagnosis

    PubMed Central

    Townsend, Anne; Backman, Catherine L; Adam, Paul; Li, Linda C

    2013-01-01

    Objective To examine accounts of medication use in participants with early rheumatoid arthritis (RA) from symptom onset to early postdiagnosis. Design Qualitative study with in-depth, personal interviews. Participants 37 women and one man, aged 30–70s, with a diagnosis of RA <12?months. Main outcome measure Participants’ experiences and feelings of medication use in early RA. Setting British Columbia, Canada. Results Medications were central to how people managed symptoms and disease. Two main themes were identified, showing that optimum medication use was hampered, and how this related to delayed diagnosis and effective care. The first theme, ‘paradox of prediagnosis reliance on over the counter (OTC) medications’, describes how people's self-management with OTC medications was ‘effective’. Participants relied extensively on OTC medications for pain relief and to maintain ‘normal life’. However, as this contributed to delayed medical consultation, diagnosis and effective treatment, OTC medication was also potentially detrimental to disease outcome. The second theme, ‘ambivalence around prescription medications post diagnosis’, describes how adherence was hindered by patient beliefs, priorities and ambivalence towards medications. Conclusions This study highlights how people use medications in early RA and contributes to a better understanding of medication use that may transfer to other conditions. Given the drive towards active self-management in healthcare and patients’ ambivalence about using strong medications, an in-depth understanding of how these combined factors impact patient experiences will help healthcare providers to support effective medication practices. The reported extensive reliance on OTC medications may speak to a care gap needing further investigation in the context of health behaviours and outcomes of patient self-management. PMID:23408077

  7. Alternative salt bridge formation in A?—a hallmark of early-onset Alzheimer's disease?

    PubMed Central

    Schledorn, Maarten; Meier, Beat H.; Böckmann, Anja

    2015-01-01

    Recently the 3D structure of the Osaka mutant form (E22?) of Amyloid-?1-40 has been determined. We here compare the NMR chemical-shift with the published shifts of a brain-seeded form of wild-type A? and suggest that the determined mutant fold is accessible to the wild-type protein as well, with small conformational adaptations which accommodate the E22 residue missing in the Osaka mutant. In addition, we illustrate how other mutants could also conform to this model. The stabilization of the N-terminal part of the protein via an intermolecular salt bridge to Lys28 may represent a common structural motif for the mutants which are related to early-onset Alzheimer disease. This feature might connect to the observed increased toxicity of the mutant forms compared to wild-type A?1-40, where the salt bridge involving Lys28 is intramolecular. PMID:25988181

  8. Therapy by laser equatorial placental dichorionization for early-onset spontaneous twin anemia-polycythemia sequence.

    PubMed

    Ishii, Keisuke; Hayashi, Shusaku; Mabuchi, Aki; Taguchi, Takako; Yamamoto, Ryo; Murata, Masaharu; Mitsuda, Nobuaki

    2014-01-01

    We report a case of twin anemia-polycythemia sequence (TAPS) treated by fetoscopic laser equatorial placental dichorionization, also known as the 'Solomon technique', at 24 weeks of gestation. TAPS was present despite the absence of fetoscopically visualized chorionic anastomoses from the donor to the recipient twin. The goal of this procedure was to prevent post-laser TAPS in cases of twin-twin transfusion syndrome. The surgery and subsequent intrauterine blood transfusion to the donor twin could result in the survival of both twins without hematologic or neurological complications. Following the surgery, a placental injection test revealed no residual anastomoses. At present, laser therapy is not always feasible for TAPS, primarily because of its difficulty. However, laser therapy using the Solomon technique could be a viable approach for early-onset TAPS, especially in difficult situations in which undetectable vascular anastomoses related to TAPS are present. PMID:24051546

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

    PubMed

    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. PMID:19161156

  10. Alu-specific microhomology-mediated deletions in CDKL5 in females with early-onset seizure disorder.

    PubMed

    Erez, Ayelet; Patel, Amina J; Wang, Xueqing; Xia, Zhilian; Bhatt, Samarth S; Craigen, William; Cheung, Sau Wai; Lewis, Richard A; Fang, Ping; Davenport, Sandra L H; Stankiewicz, Pawel; Lalani, Seema R

    2009-10-01

    Mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene in Xp22.13 have been associated with infantile spasms, early-onset intractable epilepsy, and a Rett syndrome (RTT)-like phenotype. Using array comparative genomic hybridization, we identified variable-sized microdeletions involving exons 1-4 of the CDKL5 gene in three females with early-onset seizures. Two of these deletions were flanked by Alu repetitive elements and may have resulted from either non-allelic homologous recombination or the microhomology-mediated Fork Stalling and Template Switching/Microhomology-Mediated Break-Induced Replication mechanism. Our findings demonstrate the first instance of genomic deletion as the molecular basis of CDKL5 deficiency in females and highlight the importance of exon targeted array-CGH analysis for this gene in females with drug-resistant early-onset seizures. PMID:19471977

  11. A Novel Trafficking-defective HCN4 Mutation is Associated with Early-Onset Atrial Fibrillation

    PubMed Central

    Zhang, Michael L.; Sinner, Moritz F.; Dolmatova, Elena V.; Tucker, Nathan R.; McLellan, Micheal; Shea, Marisa A.; Milan, David J.; Lunetta, Kathryn L.; Benjamin, Emelia J.; Ellinor, Patrick T.

    2014-01-01

    Background Atrial fibrillation (AF) is the most common arrhythmia, and a recent genome-wide association study identified HCN4 as a novel AF susceptibility locus. HCN4 encodes for the cardiac pacemaker channel and HCN4 mutations are associated with familial sinus bradycardia and AF. Objective To determine whether novel variants in the coding region of HCN4 contribute to the susceptibility for AF. Methods We sequenced the coding region of HCN4 for novel variants from 527 cases with early-onset AF from the Massachusetts General Hospital AF Study and 443 referents from the Framingham Heart Study. We used site-directed mutagenesis, cellular electrophysiology, immunocytochemistry and confocal microscopy to functionally characterize novel variants. Results We found the frequency of novel coding HCN4 variants was 2-fold greater for individuals with AF (seven variants) compared to the referents (three variants). We determined that one, (p.Pro257Ser, located in the amino-terminus adjacent to the first transmembrane spanning domain) of the seven novel HCN4 variants in our AF cases did not traffick to cell membrane while the remaining six were not functionally different from wild type. Also, the three novel variants in our referents did not alter function compared to wild type. Co-expression studies showed that the p.Pro257Ser mutant channel failed to co-localize with the wild type HCN4 channel on the cell membrane. Conclusion Our findings are consistent with HCN4 haploinsufficiency as the likely mechanism for early-onset AF in the p.Pro257Ser carrier. PMID:24607718

  12. Managing the Risk for Early Onset Osteoporosis in Long-Duration Astronauts Due to Spaceflight

    NASA Technical Reports Server (NTRS)

    Sibonga, Jean D.

    2010-01-01

    Early Onset Osteoporosis is probably the most recognized but poorly understood long-term health risk due to spaceflight. Osteoporosis management is primarily prophylactic and clinical interventions rely upon the ability to predict fractures which is currently determined by surrogate measures of bone strength. The RMAT for Early Onset Osteoporosis identified some open issues related to the fact that long-duration astronauts compose a unique group of subjects for which clinical approaches for osteoporosis management do not apply. Long-duration astronauts are healthy, young (25 to 55 years of age), predominantly male, and physical fit relative to the typical osteoporosis patient. Moreover, during prolonged space missions (typically 6-month missions) the skeleton not only adapts to weightlessness, but is influenced by numerous risk factors induced by operational constraints, e.g., inability to maintain preflight weight-bearing and aerobic activities, sub-optimal dietary intake (e.g., high sodium content for food stability, lack of fresh fruit and vegetables), suppression of vitamin D metabolism by uv shielding, and remote medicine care. Moreover, adaptation results in novel changes to astronauts bones that cannot be detected by current medically-useful measures. Consequently, a panel of clinicians (recognized leaders and policy-makers in osteoporosis) was convened to review the dataset of bone measures and bone loss risk factors in long-duration astronauts. Driven by the queries in the RMAT, the panel was charged to determine 1) if an intervention is required to prevent this risk, 2) what type and at what time would intervention be optimal, 3) what is the clinical trigger that would require a medical response from flight surgeons and 4) how should research data be used in the clinical care of astronauts. Hence, the RMAT determined that a bone health policy need to be formulated specific for this unique cohort subjected to a novel skeletal condition

  13. Early-onset severe preeclampsia by first trimester pregnancy-associated plasma protein a and total human chorionic gonadotropin.

    PubMed

    Jelliffe-Pawlowski, Laura L; Baer, Rebecca J; Currier, Robert J; Lyell, Deirdre J; Blumenfeld, Yair J; El-Sayed, Yasser Y; Shaw, Gary M; Druzin, Maurie L

    2015-06-01

    Objective?This study aims to evaluate the relationship between early-onset severe preeclampsia and first trimester serum levels of pregnancy-associated plasma protein A (PAPP-A) and total human chorionic gonadotropin (hCG). Study Design?The association between early-onset severe preeclampsia and abnormal levels of first trimester PAPP-A and total hCG in maternal serum were measured in a sample of singleton pregnancies without chromosomal defects that had integrated prenatal serum screening in 2009 and 2010 (n?=?129,488). Logistic binomial regression was used to estimate the relative risk (RR) of early-onset severe preeclampsia in pregnancies with abnormal levels of first trimester PAPP-A or total hCG as compared with controls. Results?Regardless of parity, women with low first trimester PAPP-A or high total hCG were at increased risk for early-onset severe preeclampsia. Women with low PAPP-A (multiple of the median [MoM]???the 10th percentile in nulliparous or???the 5th percentile in multiparous) or high total hCG (MoM???the 90th percentile in nulliparous or???the 95th percentile in multiparous) were at more than a threefold increased risk for early-onset severe preeclampsia (RR, 4.2; 95% confidence interval [CI], 3.0-5.9 and RR, 3.3; 95% CI, 2.1-5.2, respectively). Conclusion?Routinely collected first trimester measurements of PAPP-A and total hCG provide unique risk information for early-onset severe preeclampsia. PMID:25519199

  14. The Relationship Between Early Age of Onset of Initial Substance Use and Engaging in Multiple Health Risk Behaviors Among Young Adolescents

    Microsoft Academic Search

    Robert H. DuRant; Jeffrey A. Smith; Shelley R. Kreiter; Daniel P. Krowchuk

    1999-01-01

    Background: Previous research based on problem- behavior theory has found that early age of onset of sub- stance use is associated with engaging in multiple health risk behaviors among high school students. It is unknown whether these relationships begin during early adolescence. Objective: To examine the relationships between early age of onset of cigarette, alcohol, marijuana, and co- caine use

  15. Role of periodontal pathogenic bacteria in RANKL-mediated bone destruction in periodontal disease

    PubMed Central

    Kajiya, Mikihito; Giro, Gabriela; Taubman, Martin A.; Han, Xiaozhe; Mayer, Marcia P.A.; Kawai, Toshihisa

    2010-01-01

    Accumulated lines of evidence suggest that hyperimmune responses to periodontal bacteria result in the destruction of periodontal connective tissue and alveolar bone. The etiological roles of periodontal bacteria in the onset and progression of periodontal disease (PD) are well documented. However, the mechanism underlying the engagement of periodontal bacteria in RANKL-mediated alveolar bone resorption remains unclear. Therefore, this review article addresses three critical subjects. First, we discuss earlier studies of immune intervention, ultimately leading to the identification of bacteria-reactive lymphocytes as the cellular source of osteoclast-induction factor lymphokine (now called RANKL) in the context of periodontal bone resorption. Next, we consider (1) the effects of periodontal bacteria on RANKL production from a variety of adaptive immune effector cells, as well as fibroblasts, in inflamed periodontal tissue and (2) the bifunctional roles (upregulation vs. downregulation) of LPS produced from periodontal bacteria in a RANKL-induced osteoclast-signal pathway. Future studies in these two areas could lead to new therapeutic approaches for the management of PD by down-modulating RANKL production and/or RANKL-mediated osteoclastogenesis in the context of host immune responses against periodontal pathogenic bacteria. PMID:21523224

  16. Alu -specific microhomology-mediated deletions in CDKL5 in females with early-onset seizure disorder

    Microsoft Academic Search

    Ayelet Erez; Amina J. Patel; Xueqing Wang; Zhilian Xia; Samarth S. Bhatt; William Craigen; Sau Wai Cheung; Richard A. Lewis; Ping Fang; Sandra L. H. Davenport; Pawel Stankiewicz; Seema R. Lalani

    2009-01-01

    Mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene in Xp22.13 have been associated with infantile spasms, early-onset intractable epilepsy, and a Rett syndrome (RTT)-like\\u000a phenotype. Using array comparative genomic hybridization, we identified variable-sized microdeletions involving exons 1–4\\u000a of the CDKL5 gene in three females with early-onset seizures. Two of these deletions were flanked by Alu repetitive elements and may have

  17. Primary Early-Onset Dysthymia: Comparison With Primary Nonbipolar Nonchronic Major Depression on Demographic, Clinical, Familial, Personality, and Socioenvironmental Characteristics and Short-Term Outcome

    Microsoft Academic Search

    Daniel N. Klein; Ellen B. Taylor; Susan Dickstein; Kathryn Harding

    1988-01-01

    In order to explore the characteristics and validity of DSM-III-R primary early-onset dysthymia, we compared outpatients with primary early-onset dysthymia (n = 32) and primary nonbipolar nonchronic major depression (n = 35). Fifty-nine percent of the dysthymics were currently in a major depressive episode, and 97% had a history of major depression. Compared with the episodic major depressives, the early-onset

  18. The Onset of Early Season Rainfall and its Mid-Summer Cessation in the Caribbean.

    NASA Astrophysics Data System (ADS)

    Allen, T. L.; Mapes, B. E.

    2014-12-01

    The annual rainfall cycle for the Caribbean basin reveals a distinct bimodal pattern with peaks during the late spring and late summer months. A relative minimum during the mid-summer, known as the mid-summer drought (MSD) separates the early rainfall season (ERS) from the late rainfall season. Accumulated rainfall totals during the ERS appear as a quasi-stationary rain-belt stretching across the Caribbean from the southwest to the northeast. We place late spring rains in the Caribbean in context of other subtropical convergence zones in order to address the onset and cessation of the ERS while also offering an explanation of a Caribbean rain-belt pattern. Upper tropospheric westerlies, mid-tropospheric positive temperature advection, and moist low level poleward flow are the three primary ingredients that conspire to produce the first peak of the annual bimodal rain signal and the related Caribbean early season rain-belt. The MSD ensues as the primary ingredients weaken across the Caribbean and enhanced rainfall shifts north along the North Atlantic Convergence Zone (NACZ). Seasonal rainfall totals from the ERS through the MSD periods reveal a continuous rain-belt that extends from the Caribbean to the NACZ termed the Caribbean Atlantic Rain-belt (CAR-belt). The Car-belt is present in the long term mean, but has signs of interannual variability.

  19. Predictive role of high sensitive C-reactive protein in early onset mortality after ischemic stroke

    PubMed Central

    Mohebbi, Shahrzad; Ghaffarpour, Majid; Meisami, Ali Pasha; Siah, Reza Shah; Mirkala, Mohammad Reza Mousavi; Ashraf, Maryam Pour; Yaghubi, Mahbubeh

    2012-01-01

    Background High sensitive C-reactive protein (hs-CRP) is a systemic inflammatory marker that is produced in a large amount by hepatocytes in response to interleukin-1 (IL-1), IL-6 and tumor necrosis factor after ischemic stroke. Methods Measurement of hs-CRP in the first 24 hours of onset in 162 patients suffering from ischemic stroke was done. Relation of CRP with the risk of early mortality, National Institutes of Health Stroke Scale (NIHSS), stroke subtypes and other factors was determined. Results Regarding to ROC curve analysis, appropriate cut-off point for predicting patients’ short time mortality was equal to 2.15 mg/dl in this study. Significantly increased rate of mortality by 13.3 times was seen in patients with simultaneous CRP > 2.15 mg/dl and NIHSS > 10. Conclusion The Result of this study showed that there is a direct association between hs-CRP and mortality within the first week after stroke. Measuring hs-CRP within the first hours after stroke increases the predicting rate of early mortality risk with cut-off point of 2.15. PMID:24250882

  20. Early onset imatinib mesylate-induced hepatotoxicity in a patient with gastrointestinal stromal tumors.

    PubMed

    Yachoui, Ralph

    2014-01-01

    Imatinib mesylate is used for the treatment of patients with Philadelphia chromosome-positive chronic myeloid leukemia and gastrointestinal stromal tumors (GISTs). It has been associated with severe hepatotoxicity, which may lead to liver failure and death. Few cases of imatinib mesylate-induced liver failure have been reported; most of them were observed in patients treated for chronic myeloid leukemia. To date, 2 cases were reported in patients treated for GISTs. Elevation of liver function tests is usually observed during the first 2-3 months after the initiation of therapy. We report a 46-year-old woman with advanced GISTs who developed hepatotoxicity 11 days after the initiation of imatinib therapy. Before therapy with imatinib, her liver function tests were normal. She had no known risk factors for viral or alcoholic liver disease. Imatinib was her only regular medication, and she had not used acetaminophen or over-the-counter medications. Her serologic studies for hepatitis were all negative. One week after imatinib discontinuation, liver function tests improved significantly. The present report confirms the possibility of early onset imatinib mesylate-induced liver failure in patients treated for GISTs. Surveillance of liver function tests should start early after the initiation of treatment and during all the duration of therapy. PMID:23567788

  1. Predictors of early-onset permanent hearing loss in malnourished infants in Sub-Saharan Africa.

    PubMed

    Olusanya, Bolajoko O

    2011-01-01

    The objective of this study was to determine the predictors of early-onset permanent hearing loss (EPHL) among undernourished infants in a low-income country where routine screening for developmental disabilities in early childhood is currently unattainable. All infants attending four community-based clinics for routine immunization who met the criteria for undernutrition by the Growth Standards of the World Health Organization (WHO) based on weight-for-age, weight-for-length and body-mass-index-for-age were enlisted. EPHL was determined after two-stage screening with transient-evoked otoacoustic emissions, automated auditory brainstem response and diagnostic evaluation. Factors predictive of EPHL were explored with multivariable logistic regression analysis. Some 39 (1.7%) infants from 2254 undernourished infants were confirmed with hearing loss (>30 dB HL). Bilateral EPHL was mild in 7 (17.9%) and moderate-to-profound in 26 (66.7%). EPHL was unilateral in 6 (15.4%). Multiparity, chronological age of more than 30 days, the absence of skilled attendant at birth and severe neonatal jaundice were associated with an increased risk of EPHL while having a Christian mother and exclusive breast feeding had protective effect against EPHL. EPHL is highly prevalent among undernourished infants and associated with modifiable risk factors that can be addressed at the community-level and used as a basis for targeted intervention in resource-poor countries. PMID:20952158

  2. New-Onset Diabetes After Transplantation: Results From a Double-Blind Early Corticosteroid Withdrawal Trial.

    PubMed

    Pirsch, J D; Henning, A K; First, M R; Fitzsimmons, W; Gaber, A O; Reisfield, R; Shihab, F; Woodle, E S

    2015-07-01

    New-onset diabetes after transplantation (NODAT) is an important complication following kidney transplantation. Data from the 5-year early steroid withdrawal double-blind randomized trial were analyzed to determine if steroid avoidance reduced the NODAT risk. Incidence, timing and risk factors for NODAT were evaluated using eight definitions. By American Diabetes Association definition, 36.3% of patients on chronic corticosteroids (CCS) and 35.9% on early corticosteroid withdrawal (CSWD) were diagnosed with NODAT by 5 years. The definition combining fasting blood glucose ?126?mg/dL on two occasions or treatment identified slightly more cases of NODAT: CCS (39.3%) and CSWD (39.4%). Through 5 years posttransplant, the proportion of NODAT patients requiring treatment were similar (CSWD 22.5% vs. CCS 21.5%); however, insulin therapy was lower with CSWD (3.7% vs. 11.6%; p?=?0.049). By multivariate analysis, only age, but not corticosteroid use, was a significant risk factor for NODAT for more than one definition. Numerical, but not statistically significant trends toward lower NODAT rates with CSWD were observed through 5 years for insulin use, HbA1c ?6.0% and ?6.5% on two occasions. This prospective, randomized trial of CSWD indicates that CSWD has a limited impact in reducing NODAT when compared to low-dose prednisone (5?mg/day from month 6 to 5 years). PMID:25881802

  3. Early onset and origin of 100-kyr cycles in Pleistocene tropical SST records

    NASA Astrophysics Data System (ADS)

    Liu, Zhonghui; Cleaveland, Laura C.; Herbert, Timothy D.

    2008-01-01

    The large 100-kyr cycles evident in most late-Pleistocene (0-0.6 Ma) paleoclimatic records still lack a satisfactory explanation. Previous studies of the nature of the transition from the early Pleistocene (1.2-1.8 Ma) 41-kyr-dominated climate regime to the 100-kyr world have been based almost exclusively on benthic foraminiferal oxygen isotopic ( ?18O) data. It is generally accepted that the late Pleistocene 100-kyr cycles represent a newly evolved sensitivity to eccentricity/precession, superimposed on an earlier, and largely constant, response to obliquity and precession forcing. However, orbitally-resolved Pleistocene sea surface temperature (SST) records from a variety of oceanic regions paint a rather different picture of the global climate transition across the mid-Pleistocene transition (MPT, 0.6-1.2 Ma). Reanalysis of these SST records shows that: (1) an early onset of strong 100-kyr-like cycles in two low-frequency bands (˜ 120-145 kyr and ˜ 60-80 kyr), derived from the bundling of two/three obliquity cycles into grand cycles (obliquity subharmonics), occurred in tropical SST records during the early Pleistocene, (2) these two early Pleistocene periods converge into the late-Pleistocene 100-kyr period in tropical SST records, (3) the dominance of 100-kyr SST power in the late Pleistocene coincides with a dramatic decline in the 41-kyr SST power, and (4) the correlation of timing of glacial terminations with eccentricity/precession variation could well extend back into the early Pleistocene. We demonstrate that most of these features also occur in ?18O records, but in a much more subtle manner. These features could be explained in two plausible ways: a shift in climate sensitivity from obliquity to eccentricity/precession (a modified version of the conventional view) or an increasingly nonlinear response to orbital obliquity across the MPT. However, our examination of the development of ˜100-kyr cycles favors an obliquity bundling mechanism to form late Pleistocene 100-kyr cycles. We therefore suggest that the late Pleistocene 100-kyr climatic cycles are likely a nonlinear response to orbital obliquity, although the timing of late Pleistocene 100-kyr climatic cycles and their early forms appears to be paced by eccentricity/precession.

  4. Expression of collapsin response mediator protein 1 in placenta of normal gestation and link to early-onset preeclampsia.

    PubMed

    Qiao, Chong; Wang, Chunhui; Jin, Feng; Zheng, Dongying; Liu, Caixia

    2015-04-01

    A human isoform of Collapsin Response Mediator Protein (CRMP) family proteins, CRMP-1, has been identified as a novel invasion suppressor. The aim of this study was to determine CRMP-1 expression pattern in placentas during normal pregnancy and elucidate the clinical significance of CRMP-1 expression in the placentas of women with early-onset preeclamptic pregnancies. We recruited 66 normal healthy pregnant Chinese women and 60 Chinese patients with preeclampsia [early-onset prereclampsia(ePE), n = 30 and late-onset preeclampsia(lPE) n = 30]. Gestational age-matched normal healthy pregnant women were used as controls of early-onset and late-onset preeclampsia, which were 23-33 + 6 weeks, n = 18 and control B: 34-40 weeks, n = 20). Quantitative RT-PCR, Western blot analysis and immunohistochemistry were used to analyze the expressions of CRMP-1 in placentas. Expression of CRMP-1 was detected in syncytio- and cytotrophoblasts of all groups using immunohistochemistry. CRMP-1 was most abundantly expressed in syncytiotrophoblasts, moderately in cytotrophoblasts and the intermediate trophoblasts especially in the first trimester. The placental expression of CRMP-1 is particularly striking in the first trimester and decreases throughout pregnancy. There is a significant increase in CRMP-1 expression in the placenta of ePE but not of lPE, as compared to gestational-matched controls. The aberrant upregulation of CRMP-1 expression may link to the mechanism of developing ePE. PMID:25194153

  5. Frequency of activating mutations in FGFR2 exon 7 in bladder tumors from patients with early-onset and regular-onset disease

    PubMed Central

    Spiegelberg, Christine; Giedl, Johannes; Gaisa, Nadine T; Rogler, Anja; Riener, Marc-Oliver; Filbeck, Thomas; Burger, Maximilian; Ruemmele, Petra; Hartmann, Arndt; Stoehr, Robert

    2014-01-01

    The FGF/FGFR-system plays an important role in embryogenesis, tissue homeostasis and carcinogenesis. Mutational activation of FGFR2 resulting in aberrant FGFR2 signaling activation is known from both hereditary germ line alterations and somatic mutations in various malignancies (e.g. breast, gastric or ovarian cancer). FGFR2 mutations are mainly located within the hinge between Ig-like domains (exon 7), around the 3rd Ig-like domains and within the kinase domain. For bladder cancer only sparse data on FGFR2 mutations are available. Most interestingly a case of early-onset papillary carcinoma of the bladder showing a FGFR2 p.Pro253Arg mutation in exon 7 in a patient with Apert Syndrome was reported recently. To further evaluate the importance of FGFR2 exon 7 alterations in bladder cancer a cohort of 254 bladder tumors (cohort 1: unselected cases: n=139; cohort 2: early-onset bladder cancer cases (age at time of diagnosis ?45 years): n=115) was analyzed. Sections from formalin-fixed, paraffin-embedded bladder tumors were used for DNA isolation. After precise microdissection exon 7 of the FGFR2 gene was analyzed by direct Sanger sequencing. All cases could be analyzed successfully. Mutations in exon 7 of FGFR2 could not be detected in any of the cases. All tumors showed wild type sequence. Our data demonstrate that the recently reported association between early-onset papillary carcinoma of the bladder with germ line FGFR2 p.Pro253Arg mutation could not be found in our cohorts of sporadic bladder tumors. These results indicate that FGFR2 gene mutations might only play a minor role in bladder carcinogenesis. PMID:24817968

  6. Local-to-remote cortical connectivity in early- and adulthood-onset schizophrenia

    PubMed Central

    Jiang, L; Xu, Y; Zhu, X-T; Yang, Z; Li, H-J; Zuo, X-N

    2015-01-01

    Schizophrenia is increasingly thought of as a brain network or connectome disorder and is associated with neurodevelopmental processes. Previous studies have suggested the important role of anatomical distance in developing a connectome with optimized performance regarding both the cost and efficiency of information processing. Distance-related disturbances during development have not been investigated in schizophrenia. To test the distance-related miswiring profiles of connectomes in schizophrenia, we acquired resting-state images from 20 adulthood-onset (AOS) and 26 early-onset schizophrenia (EOS) patients, as well as age-matched healthy controls. All patients were drug naive and had experienced their first psychotic episode. A novel threshold-free surface-based analytic framework was developed to examine local-to-remote functional connectivity profiles in both AOS and EOS patients. We observed consistent increases of local connectivity across both EOS and AOS patients in the right superior frontal gyrus, where the connectivity strength was correlated with a positive syndrome score in AOS patients. In contrast, EOS but not AOS patients exhibited reduced local connectivity within the right postcentral gyrus and the left middle occipital cortex. These regions' remote connectivity with their interhemispheric areas and brain network hubs was altered. Diagnosis–age interactions were detectable for both local and remote connectivity profiles. The functional covariance between local and remote homotopic connectivity was present in typically developing controls, but was absent in EOS patients. These findings suggest that a distance-dependent miswiring pattern may be one of the key neurodevelopmental features of the abnormal connectome organization in schizophrenia. PMID:25966366

  7. Reading Aloud in Persian: ERP Evidence for an Early Locus of the Masked Onset Priming Effect

    ERIC Educational Resources Information Center

    Timmer, Kalinka; Vahid-Gharavi, Narges; Schiller, Niels O.

    2012-01-01

    The current study investigates reading aloud words in Persian, a language that does not mark all its vowels in the script. Behaviorally, a "masked onset priming effect" (MOPE) was revealed for transparent words, with faster speech onset latencies in the phoneme-matching condition (i.e. phonological prime and target onset overlap; e.g. [image…

  8. Two Percent of Men with Early-Onset Prostate Cancer Harbor Germline Mutations in the BRCA2 Gene

    Microsoft Academic Search

    Stephen M. Edwards; Zsofia Kote-Jarai; Julia Meitz; Rifat Hamoudi; Questa Hope; Peter Osin; Rachel Jackson; Christine Southgate; Rashmi Singh; Alison Falconer; David P. Dearnaley; Audrey Ardern-Jones; Annette Murkin; Anna Dowe; Jo Kelly; Sue Williams; Richard Oram; Margaret Stevens; Dawn M. Teare; A. J. Bruce Ponder; Simon A. Gayther; Doug F. Easton; Rosalind A. Eeles

    2003-01-01

    Studies of families with breast cancer have indicated that male carriers of BRCA2 mutations are at increased risk of prostate cancer, particularly at an early age. To evaluate the contribution of BRCA2 mutations to early-onset prostate cancer, we screened the complete coding sequence of BRCA2 for germline mutations, in 263 men with diagnoses of prostate cancer who were 55 years

  9. Warm temperatures lead to early onset of incubation, shorter incubation periods and greater hatching asynchrony in tree swallows Tachycineta bicolor at the extremes of their range

    Microsoft Academic Search

    Daniel R. Ardia; Caren B. Cooper; Andre A. Dhondt

    2006-01-01

    The onset of incubation varies in birds, with many species beginning incubation prior to clutch completion. Here we examine whether early onset is more likely to occur during high temperatures, a critical prediction of the egg-viability hypothesis, which suggest that birds begin incubation prior to clutch completion in order to maintain egg-viability. We examined onset of incubation in tree swallows

  10. A Meta-Analysis of Neuropsychological Functioning in Patients with Early Onset Schizophrenia and Pediatric Bipolar Disorder

    ERIC Educational Resources Information Center

    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…

  11. Components of Negative Affect as Moderators of the Relationship between Early Drinking Onset and Binge-Drinking Behavior

    ERIC Educational Resources Information Center

    McNamara, Robert S.; Swaim, Randall C.; Rosen, Lee A.

    2010-01-01

    This study examines the moderating effects of negative affect on the relationship between early drinking onset and binge-drinking behavior. Six hundred and thirty-five eleventh- and twelfth-grade students completed the American Drug and Alcohol Survey and reported on a variety of measures, including items assessing anxiety, anger, depression, age…

  12. Early-Onset Alcoholism With Conduct Disorder: Go\\/No Go Learning Deficits, Working Memory Capacity, and Personality

    Microsoft Academic Search

    Peter R. Finn; Carlos A. Mazas; Alicia N. Justus; Joseph Steinmetz

    2002-01-01

    Background: Two studies were conducted to investigate the disinhibitory mechanisms that (1) discrim- inate early-onset alcoholism (EOA) with conduct disorder (CD; antisocial EOA) from a nonantisocial subtype of EOA and (2) are associated with novelty-seeking and low harm avoidance. Methods: Young adults with antisocial EOA (n 96), with nonantisocial EOA (without CD; n 80), with CD alone (n 50), and

  13. Double-Blind Maintenance Safety and Effectiveness Findings from the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) Study

    ERIC Educational Resources Information Center

    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…

  14. Verbal Behavior in Young Children with Autism Spectrum Disorders at the Onset of an Early Behavioral Intervention Program

    ERIC Educational Resources Information Center

    Rivard, Melina; Forget, Jacques

    2012-01-01

    The scope of this study was direct observation of verbal behaviors of 14 children with autism spectrum disorders at the onset of an early behavioral intervention (EBI) program delivered in a public services agency. Objectives were to (1) describe frequencies of vocal, verbal, and listener behaviors; (2) evaluate the relationship between the…

  15. Low Birth Weights Contribute to the High Rates of Early-Onset Chronic Renal Failure in the Southeastern United States

    Microsoft Academic Search

    Daniel T. Lackland; Holly E. Bendall; Clive Osmond; Brent M. Egan; David J. P. Barker

    2000-01-01

    Background: The southeastern United States is a re- gion in which rates of cardiovascular and renal diseases are excessive. Within the Southeast, South Carolina has unusually high rates of end-stage renal disease (ESRD) in young people, with more than 70% of cases attrib- uted to hypertension and diabetes. Objective: To determine whether the increased vul- nerability to early-onset ESRD might

  16. Two novel mutations in the GDAP1 and PRX genes in early onset Charcot-Marie-Tooth syndrome.

    PubMed

    Auer-Grumbach, M; Fischer, C; Papi?, L; John, E; Plecko, B; Bittner, R E; Bernert, G; Pieber, T R; Miltenberger, G; Schwarz, R; Windpassinger, C; Grill, F; Timmerman, V; Speicher, M R; Janecke, A R

    2008-02-01

    Autosomal recessive Charcot-Marie-Tooth syndrome (AR-CMT) is often characterised by an infantile disease onset and a severe phenotype. Mutations in the ganglioside-induced differentiation-associated protein 1 (GDAP1) gene are thought to be a common cause of AR-CMT. Mutations in the periaxin (PRX) gene are rare. They are associated with severe demyelination of the peripheral nerves and sometimes lead to prominent sensory disturbances. To evaluate the frequency of GDAP1 and PRX mutations in early onset CMT, we examined seven AR-CMT families and 12 sporadic CMT patients, all presenting with progressive distal muscle weakness and wasting. In one family also prominent sensory abnormalities and sensory ataxia were apparent from early childhood. In three families we detected four GDAP1 mutations (L58LfsX4, R191X, L239F and P153L), one of which is novel and is predicted to cause a loss of protein function. In one additional family with prominent sensory abnormalities a novel homozygous PRX mutation was found (A700PfsX17). No mutations were identified in 12 sporadic cases. This study suggests that mutations in the GDAP1 gene are a common cause of early-onset AR-CMT. In patients with early-onset demyelinating AR-CMT and severe sensory loss PRX is one of the genes to be tested. PMID:18504680

  17. Two Novel Mutations in the GDAP1 and PRX Genes in Early Onset Charcot-Marie-Tooth Syndrome

    PubMed Central

    Auer-Grumbach, M.; Fischer, C.; Papi?, L.; John, E.; Plecko, B.; Bittner, R. E.; Bernert, G.; Pieber, T. R.; Miltenberger, G.; Schwarz, R.; Windpassinger, C.; Grill, F.; Timmerman, V.; Speicher, M. R.; Janecke, A. R.

    2011-01-01

    Autosomal recessive Charcot-Marie-Tooth syndrome (AR-CMT) is often characterised by an infantile disease onset and a severe phenotype. Mutations in the ganglioside-induced differentiation-associated protein 1 (GDAP1) gene are thought to be a common cause of AR-CMT. Mutations in the periaxin (PRX) gene are rare. They are associated with severe demyelination of the peripheral nerves and sometimes lead to prominent sensory disturbances. To evaluate the frequency of GDAP1 and PRX mutations in early onset CMT, we examined seven AR-CMT families and 12 sporadic CMT patients, all presenting with progressive distal muscle weakness and wasting. In one family also prominent sensory abnormalities and sensory ataxia were apparent from early childhood. In three families we detected four GDAP1 mutations (L58LfsX4, R191X, L239F and P153L), one of which is novel and is predicted to cause a loss of protein function. In one additional family with prominent sensory abnormalities a novel homozygous PRX mutation was found (A700PfsX17). No mutations were identified in 12 sporadic cases. This study suggests that mutations in the GDAP1 gene are a common cause of early-onset AR-CMT. In patients with early-onset demyelinating AR-CMT and severe sensory loss PRX is one of the genes to be tested. PMID:18504680

  18. Familial early onset frontotemporal dementia caused by a novel S356T MAPT mutation, initially diagnosed as schizophrenia

    Microsoft Academic Search

    Parastoo Momeni; Mirdhu M. Wickremaratchi; Jason Bell; Richard Arnold; Roger Beer; John Hardy; Tamas Revesz; James W. Neal; Huw R. Morris

    2010-01-01

    Autosomal dominant frontotemporal dementia (FTD) due to mutations in the MAPT gene is referred to as FTD with parkinsonism linked to chromosome 17 with tau pathology (FTDP-17T). Typically the disease begins in the sixth decade of life. We report a novel exon 12 mutation in MAPT (S356T), in a family with an exceptionally early age at onset (27 and 29

  19. The effect of intrapartum antibiotics on early-onset neonatal sepsis in Dhaka, Bangladesh: a propensity score matched analysis

    PubMed Central

    2014-01-01

    Background We estimate the effect of antibiotics given in the intrapartum period on early-onset neonatal sepsis in Dhaka, Bangladesh using propensity score techniques. Methods We followed 600 mother-newborn pairs as part of a cohort study at a maternity center in Dhaka. Some pregnant women received one dose of intravenous antibiotics during labor based on clinician discretion. Newborns were followed over the first seven days of life for early-onset neonatal sepsis defined by a modified version of the World Health Organization Young Infants Integrated Management of Childhood Illnesses criteria. Using propensity scores we matched women who received antibiotics with similar women who did not. A final logistic regression model predicting sepsis was run in the matched sample controlling for additional potential confounders. Results Of the 600 mother-newborn pairs, 48 mothers (8.0%) received antibiotics during the intrapartum period. Seventy-seven newborns (12.8%) were classified with early-onset neonatal sepsis. Antibiotics appeared to be protective (odds ratio 0.381, 95% confidence interval 0.115–1.258), however this was not statistically significant. The results were similar after adjusting for prematurity, wealth status, and maternal colonization status (odds ratio 0.361, 95% confidence interval 0.106–1.225). Conclusions Antibiotics administered during the intrapartum period may reduce the risk of early-onset neonatal sepsis in high neonatal mortality settings like Dhaka. PMID:24742087

  20. A novel deleterious PTEN mutation in a patient with early-onset bilateral breast cancer

    PubMed Central

    2014-01-01

    Background 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. Case presentation 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. Conclusion 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-associated carcinogenesis. PMID:24498881

  1. Laser therapy for periodontitis

    NASA Astrophysics Data System (ADS)

    Efanov, O. I.

    2001-04-01

    An investigation was made of applying pulsed (lambda) equals 0.89 micrometers laser radiation in the treatment for early diagnosed periodontitis. The investigation was made on 65 patients (47 patients constituted the experimental group and 18 patients constituted a control group) affected by periodontitis. Clinical and functional tests revealed that laser therapy produced a string effect on the course of the illness. It reduced bleeding, inflammation, and pruritus. However, it did not produce an affect on electroexcitation. Biomicroscopic examinations and periodontium rheography revealed that the gingival blood flow became normal after the course of laser therapy. The capillary permeability and venous congestion decreased, which was confirmed by the increased time of vacuum tests, raised gingival temperature, reduced tissue clearance, and increased oxygen tension. Apart from that, laser therapy subsided fibrinolysis, proteolytic tissue activity, and decreased the exudative inflammation of periodontium.

  2. Mutation in HSF4 associated with early but not late-onset hereditary cataract in the Boston Terrier.

    PubMed

    Mellersh, Cathryn S; Graves, Kathryn T; McLaughlin, Bryan; Ennis, Rosalyn B; Pettitt, Louise; Vaudin, Mark; Barnett, Keith C

    2007-01-01

    Primary hereditary cataract (HC) is one of the most common disorders in purebred dogs and is a leading cause of blindness. Boston Terriers suffer from 2 distinct forms of HC which occur at different ages and which are different in their appearance and progression. Early-onset hereditary cataract (EHC) affects dogs within the first few months of life, is always progressive and bilateral, and results in total blindness, whereas late-onset hereditary cataract (LHC) in general affects dogs over the age of 3 and is more variable in its clinical phenotype, age of onset, progression, and the degree to which vision is impaired. A mutation in HSF4 has recently been reported in a small number of Boston Terriers affected with EHC. In this study, we analyzed 22 additional Boston Terriers affected with early-onset cataract to confirm that the HSF4 mutation is causative for this form of cataract in this breed. In addition, we analyzed 40 Boston Terriers that were either clinically clear or affected with LHC for the presence or absence of the HSF4 mutation. By also sequencing HSF4 in dogs affected with LHC, we conclude that HSF4 is not associated with the development of the late-onset form of cataract and that the 2 forms of cataract in this breed are therefore genetically discrete conditions. PMID:17611257

  3. Early Pathogenesis in the Adult-Onset Neurodegenerative Disease Amyotrophic Lateral Sclerosis

    PubMed Central

    van Zundert, Brigitte; Izaurieta, Pamela; Fritz, Elsa; Alvarez, Francisco J.

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is a devastating paralytic disorder caused by dysfunction and degeneration of motor neurons starting in adulthood. Most of our knowledge about the pathophysiological mechanisms of ALS comes from transgenic mice models that emulate a subgroup of familial ALS cases (FALS), with mutations in the gene encoding superoxide dismutase (SOD1). In the more than 15 years since these mice were generated, a large number of abnormal cellular mechanisms underlying motor neuron degeneration have been identified, but to date this effort has led to few improvements in therapy, and no cure. Here, we consider that this surfeit of mechanisms is best interpreted by current insights that suggest a very early initiation of pathology in motor neurons, followed by a diversity of secondary cascades and compensatory mechanisms that mask symptoms for decades, until trauma and/or aging overloads their protective function. This view thus posits that adultonset ALS is the consequence of processes initiated during early development. In fact, motor neurons in neonatal mutant SOD mice display important alterations in their intrinsic electrical properties, synaptic inputs and morphology that are accompanied by subtle behavioral abnormalities. We consider evidence that human mutant SOD1 protein in neonatal hSOD1G93A mice instigates motor neuron degeneration by increasing persistent sodium currents and excitability, in turn altering synaptic circuits that control excessive motor neuron firing and leads to excitotoxicity. We also discuss how therapies that are aimed at suppressing abnormal neuronal activity might effectively mitigate or prevent the onset of irreversible neuronal damage in adulthood. PMID:22740507

  4. Long-Term Outcomes of Adolescents With Juvenile-Onset Fibromyalgia in Early Adulthood

    PubMed Central

    Cunningham, Natoshia; Sil, Soumitri; Bromberg, Maggie H.; Lynch-Jordan, Anne M.; Strotman, Daniel; Peugh, James; Noll, Jennie; Ting, Tracy V.; Powers, Scott W.; Lovell, Daniel J.; Arnold, Lesley M.

    2014-01-01

    OBJECTIVE: This prospective longitudinal study examined the long-term physical and psychosocial outcomes of adolescents with juvenile-onset fibromyalgia (JFM), compared with healthy control subjects, into early adulthood. METHODS: Adolescent patients with JFM initially seen at a pediatric rheumatology clinic (n = 94) and age- and gender-matched healthy control subjects (n = 33) completed online measures of demographic characteristics, pain, physical functioning, mood symptoms, and health care utilization at ?6 years’ follow-up (mean age: 21 years). A standard in-person tender-point examination was conducted. RESULTS: Patients with JFM had significantly higher pain (P < .001), poorer physical function (P < .001), greater anxiety (P < .001) and depressive symptoms (P < .001), and more medical visits (P < .001)than control subjects. The majority (>80%) of JFM patients continued to experience fibromyalgia symptoms into early adulthood, and 51.1% of the JFM sample met American College of Rheumatology criteria for adult fibromyalgia at follow-up. Patients with JFM were more likely than control subjects to be married and less likely to obtain a college education. CONCLUSIONS: Adolescent patients with JFM have a high likelihood of continued fibromyalgia symptoms into young adulthood. Those who met criteria for fibromyalgia in adulthood exhibited the highest levels of physical and emotional impairment. Emerging differences in educational attainment and marital status were also found in the JFM group. JFM is likely to be a long-term condition for many patients, and this study for the first time describes the wide-ranging impact of JFM on a variety of physical and psychosocial outcomes that seem to diverge from their same-age peers. PMID:24567017

  5. Critical slowing down as early warning for the onset of collapse in mutualistic communities

    PubMed Central

    Dakos, Vasilis; Bascompte, Jordi

    2014-01-01

    Tipping points are crossed when small changes in external conditions cause abrupt unexpected responses in the current state of a system. In the case of ecological communities under stress, the risk of approaching a tipping point is unknown, but its stakes are high. Here, we test recently developed critical slowing-down indicators as early-warning signals for detecting the proximity to a potential tipping point in structurally complex ecological communities. We use the structure of 79 empirical mutualistic networks to simulate a scenario of gradual environmental change that leads to an abrupt first extinction event followed by a sequence of species losses until the point of complete community collapse. We find that critical slowing-down indicators derived from time series of biomasses measured at the species and community level signal the proximity to the onset of community collapse. In particular, we identify specialist species as likely the best-indicator species for monitoring the proximity of a community to collapse. In addition, trends in slowing-down indicators are strongly correlated to the timing of species extinctions. This correlation offers a promising way for mapping species resilience and ranking species risk to extinction in a given community. Our findings pave the road for combining theory on tipping points with patterns of network structure that might prove useful for the management of a broad class of ecological networks under global environmental change. PMID:25422412

  6. Critical slowing down as early warning for the onset of collapse in mutualistic communities.

    PubMed

    Dakos, Vasilis; Bascompte, Jordi

    2014-12-01

    Tipping points are crossed when small changes in external conditions cause abrupt unexpected responses in the current state of a system. In the case of ecological communities under stress, the risk of approaching a tipping point is unknown, but its stakes are high. Here, we test recently developed critical slowing-down indicators as early-warning signals for detecting the proximity to a potential tipping point in structurally complex ecological communities. We use the structure of 79 empirical mutualistic networks to simulate a scenario of gradual environmental change that leads to an abrupt first extinction event followed by a sequence of species losses until the point of complete community collapse. We find that critical slowing-down indicators derived from time series of biomasses measured at the species and community level signal the proximity to the onset of community collapse. In particular, we identify specialist species as likely the best-indicator species for monitoring the proximity of a community to collapse. In addition, trends in slowing-down indicators are strongly correlated to the timing of species extinctions. This correlation offers a promising way for mapping species resilience and ranking species risk to extinction in a given community. Our findings pave the road for combining theory on tipping points with patterns of network structure that might prove useful for the management of a broad class of ecological networks under global environmental change. PMID:25422412

  7. Early onset ectopia lentis due to a FBN1 mutation with non-penetrance.

    PubMed

    Zhang, Li; Lai, Yu-Hung; Capasso, Jenina E; Han, Stella; Levin, Alex V

    2015-06-01

    Isolated ectopia lentis is usually autosomal dominant and commonly due to the mutations of FBN1 gene. We report on a family with ectopia lentis. The propositus is a 6-year-old boy with bilateral superior-temporal ectopia lentis. His echocardiogram was normal and he did not meet the revised Ghent criteria for Marfan syndrome. Molecular genetic testing revealed c.1948 C>T (p.Arg650Cys) in FBN1. The mother has visual acuity of 20/20 with -4.50 right eye and -2.50 left eye. She has no evidence of ectopia lentis. DNA analysis revealed that she has the same FBN1 mutation. Seven other maternal family members also have ectopia lentis. In conclusion, we report on a case of early-onset autosomal dominant isolated ectopia lentis caused by FBN1 mutation that has previously been reported only in Marfan syndrome. The child's mother presumably represents a rare case of nonpenetrance. © 2015 Wiley Periodicals, Inc. PMID:25900864

  8. White Matter Abnormalities and Cognitive Impairment in Early-Onset Schizophrenia-Spectrum Disorders

    PubMed Central

    Epstein, Katherine A.; Cullen, Kathryn; Mueller, Bryon; Lee, Susanne; Kumra, Sanjiv

    2014-01-01

    OBJECTIVE To characterize white matter abnormalities in adolescents with early onset schizophrenia (EOS) relative to three comparison groups (adolescents at clinical high risk for developing schizophrenia [CHR], adolescents with cannabis use disorder [CUD], and healthy controls [HC]), and to identify neurocognitive correlates of white matter abnormalities in EOS. METHOD We used diffusion tensor imaging and tractography methods to examine fractional anisotropy (FA) of the cingulum bundle, superior longitudinal fasciculus, corticospinal tract (CST), inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF), and uncinate fasciculus in adolescents with EOS (n=55), CHR (n=21), CUD (n=31), and HC (n=55). FA in tracts that were significantly altered in EOS was correlated with neurocognitive performance. RESULTS EOS and CHR groups had significantly lower FA than HC in four tracts: bilateral CST, left ILF, and left IFOF. CUD had lower FA than HC in left IFOF. Lower FA in left IFOF and left ILF predicted worse neurocognitive performance in EOS. CONCLUSIONS This study identified left ILF and left IFOF as possible biomarkers of vulnerability for developing schizophrenia. Lower FA in these tracts may disrupt functioning of ventral visual and language streams, producing domain-specific neurocognitive deficits that interfere with higher order cognitive abilities. PMID:24565363

  9. Germline DNA copy number variation in familial and early-onset breast cancer

    PubMed Central

    2012-01-01

    Introduction Genetic factors predisposing individuals to cancer remain elusive in the majority of patients with a familial or clinical history suggestive of hereditary breast cancer. Germline DNA copy number variation (CNV) has recently been implicated in predisposition to cancers such as neuroblastomas as well as prostate and colorectal cancer. We evaluated the role of germline CNVs in breast cancer susceptibility, in particular those with low population frequencies (rare CNVs), which are more likely to cause disease." Methods Using whole-genome comparative genomic hybridization on microarrays, we screened a cohort of women fulfilling criteria for hereditary breast cancer who did not carry BRCA1/BRCA2 mutations. Results The median numbers of total and rare CNVs per genome were not different between controls and patients. A total of 26 rare germline CNVs were identified in 68 cancer patients, however, a proportion that was significantly different (P = 0.0311) from the control group (23 rare CNVs in 100 individuals). Several of the genes affected by CNV in patients and controls had already been implicated in cancer. Conclusions This study is the first to explore the contribution of germline CNVs to BRCA1/2-negative familial and early-onset breast cancer. The data suggest that rare CNVs may contribute to cancer predisposition in this small cohort of patients, and this trend needs to be confirmed in larger population samples. PMID:22314128

  10. Transcriptional Onset of Lysozyme Genes during Early Development in Olive Flounder (Paralichthys olivaceus)

    PubMed Central

    Lee, Jang-Wook; Lee, Jeong-Ho; Noh, Jae Koo; Kim, Hyun Chul; Park, Choul-Ji; Park, Jong-Won; Kim, Kyung-Kil

    2014-01-01

    The immune system in teleost fish is not completely developed during embryonic and larval stages, therefore effective innate mechanisms is very important for survival in such an environment. However, the knowledge of the development of immune system assumed to be restricted. In many species, lysozymes have been considered as important genes of the first line immune defense. The early detection of lysozyme mRNA in previous reports, led to the investigation of its presence in oocytes. As a result, c-type lysozyme mRNA transcripts were detected in unfertilized oocytes indicating maternal transfer. Therefore, we investigated the expression patterns of lysozymes in flounder, including the matured oocyte. In our results, c-type lysozyme mRNA was first detected in unfertilized oocyte stage, observed the significantly decreased until hatching stage, and was significantly increased after hatching stage. On the other hand, g-type lysozyme mRNA transcripts were first detected at late neurula stage, and the mRNA level was significantly increased after 20 dph. It may be suggest that maternally supplied mRNAs are selectively degraded prior to the activation of embryonic transcription. This study will be help in understanding the maturation and onset of humoral immunity during development of olive flounder immune system. PMID:25949197

  11. Is a child's risk of early onset schizophrenia increased in the highest social class?

    PubMed

    Mäkikyrö, T; Isohanni, M; Moring, J; Oja, H; Hakko, H; Jones, P; Rantakallio, P

    1997-02-28

    In a sample from the unselected, general population Northern Finland 1966 Birth Cohort, 11017 individuals alive at the age of 16 years were studied until the age of 27. The cumulative incidence of early onset schizophrenia until 23 years was higher (1.14%; 9/792) among young persons from the highest social class or class I (determined according to father's occupation) than among children from lower social classes (0.47%; 48/10225), the difference being statistically significant (p < 0.05). The incidence of schizophrenia in the highest social class was higher than expected among girls, firstborns, children of young mothers under 30 and urban residents (p < 0.05) compared with lower social classes. When cases from the highest and other social classes were compared, there was no clear difference in background factors or clinical course. Four alcoholics, one of them also schizophrenic, were found among nine social class I fathers. The results suggest that in some families in Northern Finland, a father's professional advancement, often linked to mental disorder, may be one determinant of an increased risk of schizophrenia in the child. PMID:9075303

  12. On the early onset of the NLC season 2013 as observed at ALOMAR

    NASA Astrophysics Data System (ADS)

    Fiedler, Jens; Baumgarten, Gerd; Berger, Uwe; Gabriel, Axel; Latteck, Ralph; Lübken, Franz-Josef

    2015-05-01

    On 21 May the ALOMAR RMR-lidar in Northern Norway detected the first noctilucent clouds (NLC) in 2013. This unusual early NLC onset was accompanied by ?6 K lower temperatures and higher water vapor mixing ratios at NLC altitudes from the end of April until the beginning of June. The zonal mean temperature and dynamic conditions in the Arctic middle atmosphere deviated in spring 2013 significantly from the mean conditions of the last 20 years. Furthermore the planetary wave activity in the high latitude stratosphere was enhanced from 20 April to beginning of May. The colder and wetter upper mesosphere in May 2013 is attributed to this unusual late planetary wave activity in the stratosphere, introducing a strong upwelling in the mesosphere, lower temperatures and an upward transport of water vapor, which finally resulted in earlier existence conditions for mesospheric ice particles. We regard this as a first evidence for intra-hemispheric coupling in the northern hemisphere extending from the stratosphere into the mesopause region. Yet it is unclear whether this is an unusual extreme event or an indicator for a change in the circulation due to the observed long-term cooling of the middle atmosphere.

  13. A new clinical feature associated with familial early-onset of dystonic-guttural tics: An unusual diagnosis of PANDAS.

    PubMed

    Vitaliti, Giovanna; Trifiletti, Rosario R; Falsaperla, Raffaele; Parano, Enrico; Spalice, Alberto; Pavone, Piero

    2014-01-01

    Until today there is a large debate about the existence of PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) or PANS (pediatric acute onset neuropsychiatric syndrome). These children usually have dramatic, "overnight" onset of symptoms, including motor or vocal tics, obsessions, and/or compulsions. In addition to these symptoms, children may also have comorbid features of associated disorders. Herein, we report a family with an early onset of tics, with exclusively dystonic and guttural tics. All patients had a particularly strong excitement trigger. Two of the patients were shown to have signs suggestive of PANDAS and all family members were Group A beta-hemolytic Streptococcus (GABHS) carriers. The PANDAS spectrum is probably a group of disorders. We have described a PANDAS variant, in which the family seems to share common autoimmune pattern and may be viewed in the large spectrum of PANDAS. PMID:24891915

  14. Predictors of schizophrenia spectrum disorders in early-onset first episodes of psychosis: a support vector machine model.

    PubMed

    Pina-Camacho, Laura; Garcia-Prieto, Juan; Parellada, Mara; Castro-Fornieles, Josefina; Gonzalez-Pinto, Ana M; Bombin, Igor; Graell, Montserrat; Paya, Beatriz; Rapado-Castro, Marta; Janssen, Joost; Baeza, Inmaculada; Del Pozo, Francisco; Desco, Manuel; Arango, Celso

    2015-04-01

    Identifying early-onset schizophrenia spectrum disorders (SSD) at a very early stage remains challenging. To assess the diagnostic predictive value of multiple types of data at the emergence of early-onset first-episode psychosis (FEP), various support vector machine (SVM) classifiers were developed. The data were from a 2-year, prospective, longitudinal study of 81 patients (age 9-17 years) with early-onset FEP and a stable diagnosis during follow-up and 42 age- and sex-matched healthy controls (HC). The input was different combinations of baseline clinical, neuropsychological, magnetic resonance imaging brain volumetric and biochemical data, and the output was the diagnosis at follow-up (SSD vs. non-SSD, SSD vs. HC, and non-SSD vs. HC). Enhanced recursive feature elimination was performed for the SSD vs. non-SSD classifier to select and rank the input variables with the highest predictive value for a diagnostic outcome of SSD. After validation with a test set and considering all baseline variables together, the SSD vs. non-SSD, SSD vs. HC and non-SSD vs. HC classifiers achieved an accuracy of 0.81, 0.99 and 0.99, respectively. Regarding the SSD vs. non-SSD classifier, a combination of baseline clinical variables (severity of negative, disorganized symptoms and hallucinations or poor insight) and neuropsychological variables (impaired attention, motor coordination, and global cognition) showed the highest predictive value for a diagnostic outcome of SSD. Neuroimaging and biochemical variables at baseline did not add to the predictive value. Thus, comprehensive clinical/cognitive assessment remains the most reliable approach for differential diagnosis during early-onset FEP. SVMs may constitute promising multivariate tools in the search for predictors of diagnostic outcome in FEP. PMID:25109600

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

    Microsoft Academic Search

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

    2008-01-01

    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

  16. Huntington Disease: A Case Study of Early Onset Presenting as Depression

    ERIC Educational Resources Information Center

    Duesterhus, Pia; Schimmelmann, Benno Graf; Wittkugel, Oliver; Schulte-Markwort, Michael

    2004-01-01

    Huntington disease is a dominantly inherited, neurodegenerative disease characterized by choreiform movement disturbances and dementia, usually with adult onset. The rare juvenile-onset Huntington disease differs from the adult phenotype. A case presenting twice, at age 10 with all the signs of a major depression and age 14 with mutism and…

  17. Digging Deeper Using Neuroimaging Tools Reveals Important Clues to Early-Onset Schizophrenia

    ERIC Educational Resources Information Center

    Kumra, Sanjiv

    2008-01-01

    The article describes the use of structural neuroimaging to understand the psychopathology of childhood-onset schizophrenia. Results showed an increase in lateral volumes, reduced total and regional volumes of gray matter in the cortex and increased basal ganglia volumes as in adult-onset schizophrenia in comparison with healthy subjects.

  18. Early-onset drug use and risk of later drug problems

    Microsoft Academic Search

    James C. Anthony; Kenneth R. Petronis

    1995-01-01

    Prior research has suggested that among illicit drug users there is an increased risk of drug abuse or dependence problems associated with earlier onset of illicit drug taking. This study examined whether the observed association might be understood best as the result of a process by which earlier onset users accumulate more time during which they can develop a drug

  19. The impact of metabolic syndrome on insulin sensitivity, glucose sensitivity, and acute insulin response after glucose load in early-onset type 2 diabetes mellitus: Taiwan Early-Onset Type 2 Diabetes Cohort Study

    Microsoft Academic Search

    Chang-Hsun Hsieh; Chung-Ze Wu; Fone-Ching Hsiao; Jiunn-Diann Lin; Jer-Chuan Li; Hsiang-Lin Wan; Shi-Wen Kuo; Yi-Jen Hung; Ching-Chieh Su; Dee Pei

    2008-01-01

    Diabetic patients with metabolic syndrome (MetS) have higher lifetime risks for cardiovascular disease, especially in early-onset type 2 diabetes mellitus (EODM). Increased insulin resistance (IR) and impaired insulin secretion are important pathophysiologies in diabetic patients. Therefore, the effects of MetS on IR and insulin secretion in EODM were investigated. Forty-eight EODM (mean age, 22.8 ± 0.6 years) patients were enrolled

  20. Cognitive performance of GBA mutation carriers with early-onset PD

    PubMed Central

    Caccappolo, E.; Mejia-Santana, H.; Tang, M.-X.; Rosado, L.; Orbe Reilly, M.; Ruiz, D.; Ross, B.; Verbitsky, M.; Kisselev, S.; Louis, E.; Comella, C.; Colcher, A.; Jennings, D.; Nance, M.; Bressman, S.; Scott, W.K.; Tanner, C.; Mickel, S.; Andrews, H.; Waters, C.; Fahn, S.; Cote, L.; Frucht, S.; Ford, B.; Rezak, M.; Novak, K.; Friedman, J.H.; Pfeiffer, R.; Marsh, L.; Hiner, B.; Siderowf, A.; Payami, H.; Molho, E.; Factor, S.; Ottman, R.; Clark, L.N.; Marder, K.

    2012-01-01

    Objective: To assess the cognitive phenotype of glucocerebrosidase (GBA) mutation carriers with early-onset Parkinson disease (PD). Methods: We administered a neuropsychological battery and the University of Pennsylvania Smell Identification Test (UPSIT) to participants in the CORE-PD study who were tested for mutations in PARKIN, LRRK2, and GBA. Participants included 33 GBA mutation carriers and 60 noncarriers of any genetic mutation. Primary analyses were performed on 26 GBA heterozygous mutation carriers without additional mutations and 39 age- and PD duration–matched noncarriers. Five cognitive domains, psychomotor speed, attention, memory, visuospatial function, and executive function, were created from transformed z scores of individual neuropsychological tests. Clinical diagnoses (normal, mild cognitive impairment [MCI], dementia) were assigned blind to genotype based on neuropsychological performance and functional impairment as assessed by the Clinical Dementia Rating (CDR) score. The association between GBA mutation status and neuropsychological performance, CDR, and clinical diagnoses was assessed. Results: Demographics, UPSIT, and Unified Parkinson's Disease Rating Scale–III performance did not differ between GBA carriers and noncarriers. GBA mutation carriers performed more poorly than noncarriers on the Mini-Mental State Examination (p = 0.035), and on the memory (p = 0.017) and visuospatial (p = 0.028) domains. The most prominent differences were observed in nonverbal memory performance (p < 0.001). Carriers were more likely to receive scores of 0.5 or higher on the CDR (p < 0.001), and a clinical diagnosis of either MCI or dementia (p = 0.004). Conclusion: GBA mutation status may be an independent risk factor for cognitive impairment in patients with PD. PMID:22442429

  1. Sibling sex ratio and birth order in early-onset gender dysphoric adolescents.

    PubMed

    Schagen, Sebastian E E; Delemarre-van de Waal, Henriette A; Blanchard, Ray; Cohen-Kettenis, Peggy T

    2012-06-01

    Several sibship-related variables have been studied extensively in sexual orientation research, especially in men. Sibling sex ratio refers to the ratio of brothers to sisters in the aggregate sibships of a group of probands. Birth order refers to the probands' position (e.g., first-born, middle-born, last-born) within their sibships. Fraternal birth order refers to their position among male siblings only. Such research was extended in this study to a large group of early-onset gender dysphoric adolescents. The probands comprised 94 male-to-female and 95 female-to-male gender dysphoric adolescents. The overwhelming majority of these were homosexual or probably prehomosexual. The control group consisted of 875 boys and 914 girls from the TRAILS study. The sibling sex ratio of the gender dysphoric boys was very high (241 brothers per 100 sisters) compared with the expected ratio (106:100). The excess of brothers was more extreme among the probands' older siblings (300:100) than among their younger siblings (195:100). Between-groups comparisons showed that the gender dysphoric boys had significantly more older brothers, and significantly fewer older sisters and younger sisters, than did the control boys. In contrast, the only notable finding for the female groups was that the gender dysphoric girls had significantly fewer total siblings than did the control girls. The results for the male probands were consistent with prior speculations that a high fraternal birth order (i.e., an excess of older brothers) is found in all homosexual male groups, but an elevated sibling sex ratio (usually caused by an additional, smaller excess of younger brothers) is characteristic of gender dysphoric homosexual males. The mechanisms underlying these phenomena remain unknown. PMID:21674256

  2. Diagnostic and Sex Effects on Limbic Volumes in Early-Onset Bipolar Disorder and Schizophrenia

    PubMed Central

    Frazier, Jean A.; Hodge, Steven M.; Breeze, Janis L.; Giuliano, Anthony J.; Terry, Janine E.; Moore, Constance M.; Kennedy, David N.; Lopez-Larson, Melissa P.; Caviness, Verne S.; Seidman, Larry J.; Zablotsky, Benjamin; Makris, Nikos

    2008-01-01

    Objective: The limbic structures in early-onset schizophrenia-spectrum illness (SZ) and bipolar disorder (BPD) were studied to discern patterns associated with diagnosis and sex. Methods: Thirty-five youths with DSM-IV BPD without psychosis, 19 with BPD with psychosis, 20 with SZ, and 29 healthy controls (HC), similar in age (6-17 years) and sex, underwent structured and clinical interviews, neurological examination, and cognitive testing. Structural magnetic resonance images (MRIs) were acquired on a 1.5 Tesla, General Electric Signa Scanner. Differences in subcortical brain volumes, including the amygdala and hippocampus, were evaluated using two-way (diagnosis, sex) univariate analyses covarying for total cerebral volume and age. Results: Youth with SZ and BPD showed no differences in amygdala and hippocampal volumes. However, boys with SZ had smallest left amygdala and girls with BPD had the smallest left hippocampal volumes. In exploratory analyses, SZ showed reduced thalamic volumes bilaterally and both BPD groups had larger right nucleus accumbens (NA) volumes relative to HC. Conclusion: There were no limbic volumetric differences between BPD and SZ. However, there were diagnosis-by-sex interactions in the amygdala and hippocampus, structures that are rich in sex hormone receptors. In addition, smaller thalamus was associated with SZ while larger right NA volumes were most related to BPD. This study underscores the importance of assessing diagnostic effects and sex effects on the brain in future studies and provides evidence that boys and girls with SZ and BPD may have differential patterns of neuropathology associated with disease expression. PMID:18003631

  3. Germline variants in POLE are associated with early onset mismatch repair deficient colorectal cancer.

    PubMed

    Elsayed, Fadwa A; Kets, C Marleen; Ruano, Dina; van den Akker, Brendy; Mensenkamp, Arjen R; Schrumpf, Melanie; Nielsen, Maartje; Wijnen, Juul T; Tops, Carli M; Ligtenberg, Marjolijn J; Vasen, Hans Fa; Hes, Frederik J; Morreau, Hans; van Wezel, Tom

    2015-08-01

    Germline variants affecting the exonuclease domains of POLE and POLD1 predispose to multiple colorectal adenomas and/or colorectal cancer (CRC). The aim of this study was to estimate the prevalence of previously described heterozygous germline variants POLE c.1270C>G, p.(Leu424Val) and POLD1 c.1433G>A, p.(Ser478Asn) in a Dutch series of unexplained familial, early onset CRC and polyposis index cases. We examined 1188 familial CRC and polyposis index patients for POLE p.(Leu424Val) and POLD1 p.(Ser478Asn) variants using competitive allele-specific PCR. In addition, protein expression of the POLE and DNA mismatch repair genes was studied by immunohistochemistry in tumours from POLE carriers. Somatic mutations were screened using semiconductor sequencing. We detected three index patients (0.25%) with a POLE p.(Leu424Val) variant. In one patient, the variant was found to be de-novo. Tumours from three patients from two families were microsatellite instable, and immunohistochemistry showed MSH6/MSH2 deficiency suggestive of Lynch syndrome. Somatic mutations but no germline MSH6 and MSH2 variants were subsequently found, and one tumour displayed a hypermutator phenotype. None of the 1188 patients carried the POLD1 p.(Ser478Asn) variant. POLE germline variant carriers are also associated with a microsatellite instable CRC. POLE DNA analysis now seems warranted in microsatellite instable CRC, especially in the absence of a causative DNA mismatch repair gene germline variant. PMID:25370038

  4. No impairment of monocyte-derived Langerhans cell phenotype or function in early-onset psoriasis

    PubMed Central

    Shaw, F L; Kimber, I; Begum, R; Cumberbatch, M; Dearman, R J; Griffiths, C E M

    2012-01-01

    Background Migration of epidermal Langerhans cells (LCs) in response to the cytokines interleukin (IL)-1? and tumour necrosis factor (TNF)-? is impaired in uninvolved skin of patients with early-onset psoriasis. Aim To investigate whether this impairment is a reflection of a systemic defect in dendritic cells (DCs), using an established model of monocyte-derived LC-like cells (mLCs). Methods CD14+ monocytes isolated from both patients with psoriasis and healthy control volunteers were cultured in a cytokine cocktail for 5 days to promote their differentiation into mLCs, then stimulated for 24 h with TNF-?, IL-1? (both 100 ng/mL) or medium alone. Cellular surface protein expression was quantified by flow cytometry, and the ability of cells to migrate to media supplemented with C-C motif ligand (CCL)19 was assessed using a Transwell migration assay. The cytokine and chemokine content of supernatants was analysed by cytokine array. Results CD14+ cells acquired an LC-like phenotype with high expression of CD1a and major histocompatibility complex (MHC) class II. There were no differences in the expression of activation markers or in the secretion of cytokines by mLCs isolated from patients with psoriasis and those isolated from healthy controls. Moreover, mLCs isolated from both groups displayed comparable ability to migrate in vitro. Conclusions These data suggest that the failure of LCs to migrate in response to stimulation in patients with psoriasis is not attributable to a systemic defect in DC function, but is rather a reflection of local changes in the epidermal microenvironment. PMID:21933242

  5. Cooperative genome-wide analysis shows increased homozygosity in early onset Parkinson's disease.

    PubMed

    Simón-Sánchez, Javier; Kilarski, Laura L; Nalls, Michael A; Martinez, Maria; Schulte, Claudia; Holmans, Peter; Gasser, Thomas; Hardy, John; Singleton, Andrew B; Wood, Nicholas W; Brice, Alexis; Heutink, Peter; Williams, Nigel; Morris, Huw R

    2012-01-01

    Parkinson's disease (PD) occurs in both familial and sporadic forms, and both monogenic and complex genetic factors have been identified. Early onset PD (EOPD) is particularly associated with autosomal recessive (AR) mutations, and three genes, PARK2, PARK7 and PINK1, have been found to carry mutations leading to AR disease. Since mutations in these genes account for less than 10% of EOPD patients, we hypothesized that further recessive genetic factors are involved in this disorder, which may appear in extended runs of homozygosity.We carried out genome wide SNP genotyping to look for extended runs of homozygosity (ROHs) in 1,445 EOPD cases and 6,987 controls. Logistic regression analyses showed an increased level of genomic homozygosity in EOPD cases compared to controls. These differences are larger for ROH of 9 Mb and above, where there is a more than three-fold increase in the proportion of cases carrying a ROH. These differences are not explained by occult recessive mutations at existing loci. Controlling for genome wide homozygosity in logistic regression analyses increased the differences between cases and controls, indicating that in EOPD cases ROHs do not simply relate to genome wide measures of inbreeding. Homozygosity at a locus on chromosome19p13.3 was identified as being more common in EOPD cases as compared to controls. Sequencing analysis of genes and predicted transcripts within this locus failed to identify a novel mutation causing EOPD in our cohort.There is an increased rate of genome wide homozygosity in EOPD, as measured by an increase in ROHs. These ROHs are a signature of inbreeding and do not necessarily harbour disease-causing genetic variants. Although there might be other regions of interest apart from chromosome 19p13.3, we lack the power to detect them with this analysis. PMID:22427796

  6. Higher filtration fraction in formerly early-onset preeclamptic women without comorbidity.

    PubMed

    Toering, Tsjitske J; van der Graaf, Anne Marijn; Visser, Folkert W; Groen, Henk; Faas, Marijke M; Navis, Gerjan; Lely, A Titia

    2015-04-15

    Formerly preeclamptic women have an increased risk for developing end-stage renal disease, which has been attributed to altered renal hemodynamics and abnormalities in the renin-angiotensin-aldosterone system. Whether this is due to preeclampsia itself or to comorbid conditions is unknown. Renal hemodynamics and responsiveness to ANG II during low Na(+) intake (7 days, 50 mmol Na(+)/24 h) and high Na(+) (HS) intake (7 days, 200 mmol Na(+)/24 h) were studied in 18 healthy normotensive formerly early-onset preeclamptic women (fPE women) and 18 healthy control subjects (fHP women), all selected for absence of comorbidity. At the end of each diet, renal hemodynamics and blood pressure were measured before and during graded ANG II infusion. Both HS intake and former preeclampsia increased filtration fraction (FF) without an interaction between the two. FF was highest during HS intake in fPE women [0.31 ± 0.12 vs. 0.29 ± 0.11 in fHP women, generalized estimating equation analysis (body mass index corrected), P = 0.03]. The renal response to ANG II infusion was not different between groups. In conclusion, fPE women have a higher FF compared with fHP women. As this was observed in the absence of comorbidity, preeclampsia itself might exert long-term effects on renal hemodynamics. However, we cannot exclude the presence of prepregnancy alterations in renal function, which, in itself, lead to an increased risk for preeclampsia. In experimental studies, an elevated FF has been shown to play a pathogenic role in the development of hypertension and renal damage. Future studies, however, should evaluate whether the subtle differences in renal hemodynamics after preeclampsia contribute to the increased long-term renal risk after preeclampsia. PMID:25694481

  7. Early Onset Neonatal Sepsis: The Burden of Group B Streptococcal and E. coli Disease Continues

    PubMed Central

    Hansen, Nellie I.; Sánchez, Pablo J.; Faix, Roger G.; Poindexter, Brenda B.; Van Meurs, Krisa P.; Bizzarro, Matthew J.; Goldberg, Ronald N.; Frantz, Ivan D.; Hale, Ellen C.; Shankaran, Seetha; Kennedy, Kathleen; Carlo, Waldemar A.; Watterberg, Kristi L.; Bell, Edward F.; Walsh, Michele C.; Schibler, Kurt; Laptook, Abbot R.; Shane, Andi L.; Schrag, Stephanie J.; Das, Abhik; Higgins, Rosemary D.

    2011-01-01

    BACKGROUND: Guidelines for prevention of group B streptococcal (GBS) infection have successfully reduced early onset (EO) GBS disease. Study results suggest that Escherichia coli is an important EO pathogen. OBJECTIVE: To determine EO infection rates, pathogens, morbidity, and mortality in a national network of neonatal centers. METHODS: Infants with EO infection were identified by prospective surveillance at Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Network centers. Infection was defined by positive culture results for blood and cerebrospinal fluid obtained from infants aged ?72 hours plus treatment with antibiotic therapy for ?5 days. Mother and infant characteristics, treatments, and outcomes were studied. Numbers of cases and total live births (LBs) were used to calculate incidence. RESULTS: Among 396 586 LBs (2006–2009), 389 infants developed EO infection (0.98 cases per 1000 LBs). Infection rates increased with decreasing birth weight. GBS (43%, 0.41 per 1000 LBs) and E coli (29%, 0.28 per 1000 LBs) were most frequently isolated. Most infants with GBS were term (73%); 81% with E coli were preterm. Mothers of 67% of infected term and 58% of infected preterm infants were screened for GBS, and results were positive for 25% of those mothers. Only 76% of mothers with GBS colonization received intrapartum chemoprophylaxis. Although 77% of infected infants required intensive care, 20% of term infants were treated in the normal newborn nursery. Sixteen percent of infected infants died, most commonly with E coli infection (33%). CONCLUSION: In the era of intrapartum chemoprophylaxis to reduce GBS, rates of EO infection have declined but reflect a continued burden of disease. GBS remains the most frequent pathogen in term infants, and E coli the most significant pathogen in preterm infants. Missed opportunities for GBS prevention continue. Prevention of E coli sepsis, especially among preterm infants, remains a challenge. PMID:21518717

  8. An Inherited Small Microdeletion at 15q13.3 in a Patient with Early- Onset Obsessive-Compulsive Disorder

    PubMed Central

    Cappi, Carolina; Hounie, Ana Gabriela; Mariani, Daniel B.; Diniz, Juliana Belo; Silva, Aderbal R. T.; Reis, Viviane N. S.; Busso, Ariane F.; Silva, Amanda Gonçalves; Fidalgo, Felipe; Rogatto, Silvia Regina; Miguel, Euripedes C.; Krepischi, Ana C.; Brentani, Helena

    2014-01-01

    Copy number variations (CNVs) have been previously associated with several different neurodevelopmental psychiatric disorders, such as autism, schizophrenia, and attention deficit hyperactivity disorder (ADHD). The present study consisted of a pilot genome-wide screen for CNVs in a cohort of 16 patients with early-onset obsessive-compulsive disorder (OCD) and 12 mentally healthy individuals, using array-based comparative genomic hybridization (aCGH) on 44K arrays. A small rare paternal inherited microdeletion (?64 kb) was identified in chromosome 15q13.3 of one male patient with very early onset OCD. The father did not have OCD. The deletion encompassed part of the FMN1 gene, which is involved with the glutamatergic system. This finding supports the hypothesis of a complex network of several genes expressed in the brain contributing for the genetic risk of OCD, and also supports the glutamatergic involvement in OCD, which has been previously reported in the literature. PMID:25303678

  9. Fathering and Early Onset Conduct Problems: Positive and Negative Parenting, Father–Son Attachment, and the Marital Context

    Microsoft Academic Search

    Michelle DeKlyen; Matthew L. Speltz; Mark T. Greenberg

    1998-01-01

    Research literature linking negative and positive aspects of the father–child relationship with early onset conduct problems is reviewed. Evidence from the Preschool Families Project, a longitudinal study of clinic-referred preschool boys at risk for conduct disorder, is presented, including previously unpublished data on father–child attachment. Both negative (e.g., harsh, angry, and physically punitive) and positive (involvement, warmth, and secure attachment)

  10. Prevalence of BRCA1 and BRCA2 Gene Mutations in Patients With Early-Onset Breast Cancer

    Microsoft Academic Search

    Julian Peto; Nadine Collins; Rita Barfoot; Sheila Seal; William Warren; Nazneen Rahman; Douglas F. Easton; Christopher Evans; Judith Deacon; Michael R. Stratton

    1999-01-01

    Background: Mutations in the BRCA1 and BRCA2 genes are found in most families with cases of both breast and ovarian cancer or with many cases of early-onset breast cancer. However, in an outbred population, the prevalence of BRCA1 and BRCA2 mutations in patients with breast can- cer who were unselected for a family history of this disease has not been

  11. Six Novel Susceptibility Loci for Early-Onset Androgenetic Alopecia and Their Unexpected Association with Common Diseases

    Microsoft Academic Search

    Rui Li; Felix F. Brockschmidt; Amy K. Kiefer; Hreinn Stefansson; Dale R. Nyholt; Kijoung Song; Sita H. Vermeulen; Stavroula Kanoni; Daniel Glass; Sarah E. Medland; Maria Dimitriou; Dawn Waterworth; Joyce Y. Tung; Frank Geller; Stefanie Heilmann; Axel M. Hillmer; Veronique Bataille; Sibylle Eigelshoven; Sandra Hanneken; Susanne Moebus; Christine Herold; Martin den Heijer; Grant W. Montgomery; Panos Deloukas; Nicholas Eriksson; Andrew C. Heath; Tim Becker; Patrick Sulem; Massimo Mangino; Peter Vollenweider; Tim D. Spector; George Dedoussis; Nicholas G. Martin; Lambertus A. Kiemeney; Vincent Mooser; Kari Stefansson; David A. Hinds; Markus M. Nöthen; J. Brent Richards

    2012-01-01

    Androgenetic alopecia (AGA) is a highly heritable condition and the most common form of hair loss in humans. Susceptibility loci have been described on the X chromosome and chromosome 20, but these loci explain a minority of its heritable variance. We conducted a large-scale meta-analysis of seven genome-wide association studies for early-onset AGA in 12,806 individuals of European ancestry. While

  12. Neutrophil CD11b Expression and Circulating Interleukin8 as Diagnostic Markers for Early-Onset Neonatal Sepsis

    Microsoft Academic Search

    Irmeli Nupponen; Sture Andersson; Anna-Liisa Jarvenpaa; Hannu Kautiainen; Heikki Repo

    2001-01-01

    Objective. To assess neutrophil CD11b and circulating interleukin 8 (IL-8) as markers of early- onset infection in neonates. Methods. The study comprised 39 neonates, with a gestational age of 29 to 41 weeks, suspected of infection within 48 hours of life. Neutrophil surface expression of CD11b was quantified with flow cytometry and plasma IL-8 with an enzyme-linked immunosorbent assay. Both

  13. Impaired facial expression recognition in children with temporal lobe epilepsy: Impact of early seizure onset on fear recognition

    Microsoft Academic Search

    Nathalie Golouboff; Nicole Fiori; Olivier Delalande; Martine Fohlen; Georges Dellatolas; Isabelle Jambaqué

    2008-01-01

    The amygdala has been implicated in the recognition of facial emotions, especially fearful expressions, in adults with early-onset right temporal lobe epilepsy (TLE). The present study investigates the recognition of facial emotions in children and adolescents, 8–16 years old, with epilepsy. Twenty-nine subjects had TLE (13 right, 16 left) and eight had fronto-central epilepsy (FCE). Each was matched on age

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

    Microsoft Academic Search

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

    2002-01-01

    BACKGROUND: 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. METHODS: With the collaboration of two main centres for cancer in Iran, we obtained clinical information,

  15. The efficacy of goniotomy\\/trabeculotomy in early-onset glaucoma associated with the Sturge-Weber syndrome

    Microsoft Academic Search

    Karl E. Olsen; Agnes S. Huang; Martha M. Wright

    1998-01-01

    Purpose: To assess the efficacy of goniotomy\\/trabeculotomy as the initial surgical procedure in early-onset glaucoma associated with Sturge-Weber syndrome. Methods: We retrospectively analyzed 16 eyes of 14 consecutive patients with Sturge-Weber syndrome-associated glaucoma diagnosed before 4 years of age. All subjects were seen at a single institution from 1978 to 1996 and underwent goniotomy or trabeculotomy as their initial surgical

  16. [Diabetes and periodontitis: A bidirectional relationship].

    PubMed

    Bascones-Martínez, Antonio; Muñoz-Corcuera, Marta; Bascones-Ilundain, Jaime

    2015-07-01

    Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, a defect in insulin action or a combination of both. Periodontitis is now considered a chronic localized infection of the oral cavity that can trigger inflammatory host immune responses at local and systemic levels, and can also be a source of bacteremia. It is now known that periodontitis has an influence on the pathogenesis of certain systemic diseases. The biological relationship between diabetes and periodontal disease is well documented. In the mid-90s sufficient scientific support for the association between diabetes and periodontitis was published, and periodontitis was designated as the sixth complication of diabetes. There have been studies that show an improvement in both clinical and immunological parameters of periodontitis and glycemic control in long-term diabetes after treatment of periodontal disease. In addition, scientific evidence confirms that poorer glycemic control contributes to a worse periodontal condition. The interplay between the 2 conditions highlights the importance of the need for a good communication between the internist and dentist about diabetic patients, considering always the possibility that the 2 diseases may be occurring simultaneously in order to ensure an early diagnosis of both. PMID:25192582

  17. Treatment of early-onset multiple sclerosis with intramuscular interferon?-1a: long-term results

    Microsoft Academic Search

    A. Ghezzi; M. P. Amato; M. Capobianco; P. Gallo; M. G. Marrosu; V. Martinelli; C. Milanese; L. Moiola; N. Milani; L. La Mantia; F. Patti; C. Pozzilli; M. Trojano; G. Comi; M. Zaffaroni

    2007-01-01

    The objective was to evaluate the safety, tolerability and effectiveness of intramuscular (IM) interferon beta-1a (IFN?-1a;\\u000a Avonex, Biogen) 30 mg once a week in patients with onset of symptoms of multiple sclerosis (MS) in childhood or adolescence.\\u000a Patients with a diagnosis of definite MS according to McDonald’s criteria, relapsing course according to Lublin’s criteria,\\u000a onset of symptoms of MS before

  18. Periodontal Disease: Causes and Prevention

    MedlinePLUS

    Periodontal Disease: Causes and Prevention What Is Periodontal Disease? What Causes Periodontal Disease? Risks and Prevention What Is Periodontal Disease? If your hands bled when you washed them, you would be concerned. ...

  19. Mutation screen and association studies for the fatty acid amide hydrolase (FAAH) gene and early onset and adult obesity

    PubMed Central

    2010-01-01

    Background The orexigenic effects of cannabinoids are limited by activation of the endocannabinoid degrading enzyme fatty acid amide hydrolase (FAAH). The aim of this study was to analyse whether FAAH alleles are associated with early and late onset obesity. Methods We initially assessed association of five single nucleotide polymorphisms (SNPs) in FAAH with early onset extreme obesity in up to 521 German obese children and both parents. SNPs with nominal p-values ? 0.1 were subsequently analysed in 235 independent German obesity families. SNPs associated with childhood obesity (p-values ? 0.05) were further analysed in 8,491 adult individuals of a population-based cohort (KORA) for association with adult obesity. One SNP was further analysed in 985 German obese adults and 588 normal and underweight controls. In parallel, we screened the FAAH coding region for novel sequence variants in 92 extremely obese children using single-stranded-conformation-polymorphism-analysis and denaturing HPLC and assessed the implication of the identified new variants for childhood obesity. Results The trio analysis revealed some evidence for an association of three SNPs in FAAH (rs324420 rs324419 and rs873978) with childhood obesity (two-sided p-values between 0.06 and 0.10). Although analyses of these variants in 235 independent obesity families did not result in statistically significant effects (two-sided p-values between 0.14 and 0.75), the combined analysis of all 603 obesity families supported the idea of an association of two SNPs in FAAH (rs324420 and rs2295632) with early onset extreme obesity (p-values between 0.02 and 0.03). No association was, however, found between these variants and adult obesity. The mutation screen revealed four novel variants, which were not associated with early onset obesity (p > 0.05). Conclusions As we observed some evidence for an association of the FAAH variants rs2295632 rs324420 with early onset but not adult obesity, we conclude that the FAAH variants analyzed here at least do not seem to play a major role in the etiology of obesity within our samples. PMID:20044928

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

    PubMed Central

    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 < .001). A structural model was developed that modeled two latent parenting constructs: (a) 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 prevention programs. PMID:20409440

  1. High-frequency 3D echodentographic imaging modality for early assessment of periodontal diseases: in vitro study

    NASA Astrophysics Data System (ADS)

    Mahmoud, Ahmed M.; Ngan, Peter; Crout, Richard; Mukdadi, Osama M.

    2009-02-01

    The use of ultrasound in dentistry is still an open growing area of research. Currently, there is a lack of imaging modalities to accurately predict minute structures and defects in the jawbone. In particular, the inability of 2D radiographic images to detect bony periodontal defects resulted from infection of the periodontium. This study investigates the feasibility of high frequency ultrasound to reconstruct high resolution 3D surface images of human jawbone. Methods: A dentate and non-dentate mandibles were used in this study. The system employs high frequency single-element ultrasound focused transducers (15-30 MHz) for scanning. Continuous acquisition using a 1 GHz data acquisition card is synchronized with a high precision two-dimensional stage positioning system of +/-1 ?m resolution for acquiring accurate and quantitative measurements of the mandible in vitro. Radio frequency (RF) signals are acquired laterally 44-45.5 ?m apart for each frame. Different frames are reconstructed 500 ?m apart for the 3D reconstruction. Signal processing algorithms are applied on the received ultrasound signals for filtering, focusing, and envelope detection before frame reconstruction. Furthermore, an edge detection technique is adopted to detect the bone surface in each frame. Finally, all edges are combined together in order to render a 3D surface image of the jawbone. Major anatomical landmarks on the resultant images were confirmed with the anatomical structures on the mandibles to show the efficacy of the system. Comparison were also made with conventional 2D radiographs to show the superiority of the ultrasound imaging system in diagnosing small defects in the lateral, axial and elevation planes of space. Results: The landmarks on all ultrasound images matched with those on the mandible, indicating the efficacy of the system in detecting small structures in human jaw bones. Comparison with conventional 2D radiographic images of the same mandible showed superiority of the 3D ultrasound images in detecting defects in the elevation plane of space. These results suggest that the high frequency ultrasound system shows great potential in providing a non-invasive method to characterize the jawbone and detect periodontal diseases at earlier stages.

  2. The apolipoprotein E ? 2 allele is associated with an increased risk of early-onset Alzheimer's disease and a reduced survival

    Microsoft Academic Search

    Duijn van C. M; Peter de Knijff; Anita Wehnert; Joke De Voecht; Juliana B. Bronzova; Louis M. Havekes; Broeckhoven van C; A. Hofman

    1995-01-01

    It was suggested that in contrast to the E4 allele, the E2 allele of the apolipoprotein E gene (APOE*2) has a protective effect for late-onset Alzheimer's disease and early-onset Alzheimer's disease (EOAD). We studied the role of the APOE*2 allele in the pathogenesis of EOAD in a Dutch population-based study of 175 probable EOAD patients with onset age at or

  3. A longitudinal study of differences in late- and early-onset geriatric depression: Depressive symptoms and psychosocial, cognitive, and neurological functioning

    Microsoft Academic Search

    Natalie Sachs-Ericsson; Elizabeth Corsentino; Jerad Moxley; Jennifer L. Hames; Nicole C. Rushing; Kathryn Sawyer; Thomas Joiner; Edward A. Selby; Steven Zarit; Ian H. Gotlib; David C. Steffens

    2012-01-01

    Objectives: Studies suggest early-onset depression (EOD) is associated with a more severe course of the depressive disorder, while late-onset depression (LOD) is associated with more cognitive and neuroimaging changes. This study examined if older adults with EOD, compared with those with LOD, would exhibit more severe symptoms of depression and, consistent with the glucocorticoid cascade hypothesis, have more hippocampal volume

  4. Impaired Phagocytosis in Localized Aggressive Periodontitis: Rescue by Resolvin E1

    PubMed Central

    Fredman, Gabrielle; Oh, Sungwhan F.; Ayilavarapu, Srinivas; Hasturk, Hatice; Serhan, Charles N.; Van Dyke, Thomas E.

    2011-01-01

    Resolution of inflammation is an active temporally orchestrated process demonstrated by the biosynthesis of novel proresolving mediators. Dysregulation of resolution pathways may underlie prevalent human inflammatory diseases such as cardiovascular diseases and periodontitis. Localized Aggressive Periodontitis (LAP) is an early onset, rapidly progressing form of inflammatory periodontal disease. Here, we report increased surface P-selectin on circulating LAP platelets, and elevated integrin (CD18) surface expression on neutrophils and monocytes compared to healthy, asymptomatic controls. Significantly more platelet-neutrophil and platelet-monocyte aggregates were identified in circulating whole blood of LAP patients compared with asymptomatic controls. LAP whole blood generates increased pro-inflammatory LTB4 with addition of divalent cation ionophore A23187 (5 µM) and significantly less, 15-HETE, 12-HETE, 14-HDHA, and lipoxin A4. Macrophages from LAP subjects exhibit reduced phagocytosis. The pro-resolving lipid mediator, Resolvin E1 (0.1–100 nM), rescues the impaired phagocytic activity in LAP macrophages. These abnormalities suggest compromised resolution pathways, which may contribute to persistent inflammation resulting in establishment of a chronic inflammatory lesion and periodontal disease progression. PMID:21935407

  5. Long-Term implications of early onset in bipolar disorder: data from the first 1000 participants in the systematic treatment enhancement program for bipolar disorder (STEP-BD)

    Microsoft Academic Search

    Roy H. Perlis; Sachiko Miyahara; Lauren B. Marangell; Stephen R. Wisniewski; Michael Ostacher; Melissa P. DelBello; Charles L. Bowden; Gary S. Sachs; Andrew A. Nierenberg

    2004-01-01

    BackgroundEarly onset of mood symptoms in bipolar disorder has been associated with poor outcome in many studies; however, the factors that might contribute to poor outcome have not been adequately investigated.

  6. A Japanese family with early-onset ataxia with motor and sensory neuropathy

    Microsoft Academic Search

    Shunsuke Kobayashi; Hiroshi Takuma; Shigeo Murayama; Masaki Sakurai; Ichiro Kanazawa

    2007-01-01

    We report the case of a Japanese family with hereditary ataxia with peripheral neuropathy. Three affected siblings from this family exhibited very similar clinical features: teenage-onset, slowly progressive ataxia, followed by distal weakness, which developed after the age of 30 years. Magnetic resonance imaging studies showed marked atrophy in the cerebellar hemisphere and vermis, and a sural nerve biopsy revealed a

  7. Prolonged QT interval at onset of acute myocardial infarction in predicting early phase ventricular tachycardia

    Microsoft Academic Search

    G. J. Taylor; R. S. Crampton; R. S. Gibson; P. T. Stebbins; M. T. Waldman; G. A. Beller

    1981-01-01

    The prospectively assessed time course of changes in ventricular repolarization during acute myocardial infarction (AMI) is reported in 32 patients admitted 2.0 +\\/- 1.8 (SD) hours after AMI onset. The initial corrected QT interval (QTc) upon hospitalization was longer in the 14 patients developing ventricular tachycardia (VT) within the first 48 hours as compared to QTc in the eight patients

  8. A missense mutation disrupting a dibasic prohormone processing site in pro-opiomelanocortin (POMC) increases susceptibility to early-onset obesity through a novel molecular mechanism

    Microsoft Academic Search

    Benjamin G. Challis; Lynn E. Pritchard; John W. M. Creemers; Jerome Delplanque; Julia M. Keogh; Nicholas J. Wareham; Giles S. H. Yeo; Sumit Bhattacharyya; Phillipe Froguel; Anne White; I. Sadaf Farooqi; Stephen O'Rahilly

    2002-01-01

    The functional loss of both alleles of the human pro-opiomelanocortin (POMC) gene leads to a very rare syndrome of hypoadrenalism, red hair and early-onset obesity. In order to examine whether more subtle genetic variants in POMC might contribute to early-onset obesity, the coding region of the gene was sequenced in 262 Caucasian subjects with a history of severe obesity from

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

    PubMed Central

    2010-01-01

    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 somatic mutation of BRAF. PMID:20444249

  10. Gum (Periodontal) Disease

    MedlinePLUS

    ... Disease: What Is Gum (Periodontal) Disease? In This Topic What Is Gum (Periodontal) Disease? Risk Factors and ... for More Information National Institute on Aging Related Topics Problems with Taste The information in this topic ...

  11. Clinical whole-genome sequencing in severe early-onset epilepsy reveals new genes and improves molecular diagnosis.

    PubMed

    Martin, Hilary C; Kim, Grace E; Pagnamenta, Alistair T; Murakami, Yoshiko; Carvill, Gemma L; Meyer, Esther; Copley, Richard R; Rimmer, Andrew; Barcia, Giulia; Fleming, Matthew R; Kronengold, Jack; Brown, Maile R; Hudspith, Karl A; Broxholme, John; Kanapin, Alexander; Cazier, Jean-Baptiste; Kinoshita, Taroh; Nabbout, Rima; Bentley, David; McVean, Gil; Heavin, Sinéad; Zaiwalla, Zenobia; McShane, Tony; Mefford, Heather C; Shears, Deborah; Stewart, Helen; Kurian, Manju A; Scheffer, Ingrid E; Blair, Edward; Donnelly, Peter; Kaczmarek, Leonard K; Taylor, Jenny C

    2014-06-15

    In severe early-onset epilepsy, precise clinical and molecular genetic diagnosis is complex, as many metabolic and electro-physiological processes have been implicated in disease causation. The clinical phenotypes share many features such as complex seizure types and developmental delay. Molecular diagnosis has historically been confined to sequential testing of candidate genes known to be associated with specific sub-phenotypes, but the diagnostic yield of this approach can be low. We conducted whole-genome sequencing (WGS) on six patients with severe early-onset epilepsy who had previously been refractory to molecular diagnosis, and their parents. Four of these patients had a clinical diagnosis of Ohtahara Syndrome (OS) and two patients had severe non-syndromic early-onset epilepsy (NSEOE). In two OS cases, we found de novo non-synonymous mutations in the genes KCNQ2 and SCN2A. In a third OS case, WGS revealed paternal isodisomy for chromosome 9, leading to identification of the causal homozygous missense variant in KCNT1, which produced a substantial increase in potassium channel current. The fourth OS patient had a recessive mutation in PIGQ that led to exon skipping and defective glycophosphatidyl inositol biosynthesis. The two patients with NSEOE had likely pathogenic de novo mutations in CBL and CSNK1G1, respectively. Mutations in these genes were not found among 500 additional individuals with epilepsy. This work reveals two novel genes for OS, KCNT1 and PIGQ. It also uncovers unexpected genetic mechanisms and emphasizes the power of WGS as a clinical tool for making molecular diagnoses, particularly for highly heterogeneous disorders. PMID:24463883

  12. Tea, coffee, and caffeine and early-onset basal cell carcinoma in a case-control study.

    PubMed

    Ferrucci, Leah M; Cartmel, Brenda; Molinaro, Annette M; Leffell, David J; Bale, Allen E; Mayne, Susan T

    2014-07-01

    Tea and coffee are hypothesized to play a protective role in skin carcinogenesis through bioactive components, such as caffeine, yet the epidemiologic evidence is mixed. Existing data support an inverse association with basal cell carcinoma (BCC), more so than for melanoma or squamous cell carcinoma. To understand whether tea, coffee, and caffeine are related to early-onset BCC, we evaluated data from 767 non-Hispanic Whites under age 40 in a case-control study in Connecticut. BCC cases (n=377) were identified through Yale's Dermatopathology database. Controls (n=390) were randomly sampled from individuals in the same database with benign skin diagnoses and frequency matched to cases on age, sex, and biopsy site. Participants completed an in-person interview including assessment of caffeinated coffee and hot tea. We calculated multivariate odds ratios (ORs) and 95% confidence intervals (CIs) with unconditional logistic regression for regular consumption and frequency and duration measures. Combined regular consumption of caffeinated coffee plus hot tea was inversely associated with early-onset BCC (OR=0.60, 95% CI=0.38-0.96). Those in the highest category of caffeine from these sources had a 43% reduced risk of BCC compared with nonconsumers (OR=0.57, 95% CI=0.34-0.95, P-trend=0.037). Our findings suggest a modest protective effect for caffeinated coffee plus tea in relation to early-onset BCC that may, in part, be due to caffeine. This study adds to the growing body of literature suggesting potential health benefits from these beverages. PMID:24841641

  13. Compound heterozygosity for two MSH6 mutations in a patient with early onset colorectal cancer, vitiligo and systemic lupus erythematosus.

    PubMed

    Rahner, Nils; Höefler, Gerald; Högenauer, Christoph; Lackner, Caroline; Steinke, Verena; Sengteller, Marlies; Friedl, Waltraut; Aretz, Stefan; Propping, Peter; Mangold, Elisabeth; Walldorf, Constanze

    2008-05-15

    Lynch syndrome (hereditary non-polyposis colorectal cancer, HNPCC) is an autosomal dominant condition caused by heterozygous germline mutations in the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, or PMS2. Rare cases have been reported of an inherited bi-allelic deficiency of MMR genes, associated with multiple café-au-lait spots, early onset CNS tumors, hematological malignancies, and early onset gastrointestinal neoplasia. We report on a patient with vitiligo in segments of the integument who developed systemic lupus erythematosus (SLE) at the age of 16, and four synchronous colorectal cancers at age 17 years. Examination of the colorectal cancer tissue showed high microsatellite instability (MSI-H) and an exclusive loss of expression of the MSH6 protein. Immunohistochemical analysis of normal colon tissue also showed loss of MSH6, pointing to a bi-allelic MSH6 mutation. Sequencing of the MSH6 gene showed the two germline mutations; c.1806_1809delAAAG;p.Glu604LeufsX5 and c.3226C > T;p.Arg1076Cys. We confirmed that the two mutations are on two different alleles by allele-specific PCR. To our knowledge, neither parent is clinically affected. They did not wish to be tested for the mutations identified in their daughter. These data suggest that bi-allelic mutations of one of the MMR genes should be considered in patients who develop early-onset multiple HNPCC-associated tumors and autoimmune disorders, even in absence of either hematological malignancies or brain tumors. PMID:18409202

  14. Early-Onset Atopic Dermatitis in Children: Which Are the Phenotypes at Risk of Asthma? Results from the ORCA Cohort

    PubMed Central

    Amat, Flore; Saint-Pierre, Philippe; Bourrat, Emmanuelle; Nemni, Ariane; Couderc, Rémy; Boutmy-Deslandes, Emmanuelle; Sahraoui, Fatiha; Pansé, Isabelle; Bagot, Martine; Foueré, Sébastien; Just, Jocelyne

    2015-01-01

    Background Atopic dermatitis (AD) is known to predate asthma and other atopic disorders described under the term “atopic march”. However, this classic sequence is not always present and only a few studies have addressed children at risk of developing asthma. The objective of this study is to define early-onset AD phenotypes leading to asthma. Methods We performed a cluster analysis with 9 variables of 214 infants with early-onset AD prospectively enrolled in the ORCA cohort and followed each year on the occurrence of asthma until the age of 6. Results We identified 3 clusters - cluster 1 (n = 94) with low to no sensitization to food (27.7%) or aeroallergens (10.6%) and moderate AD severity (SCORAD 25.29 +/- 14.6) called “AD with low sensitization”; - cluster 2 (n = 84) characterized by a higher AD severity (SCORAD 32.66+/-16.6) and frequent sensitization to food (98.9%) or aeroallergens (26.2%), most likely multiple (96.4% for food allergens), called “AD with multiple sensitizations” - cluster 3 (n = 36) with parental history, moderate AD severity (SCORAD 24.46+/-15.7), moderate rate of sensitization to food allergens (38.9%) (exclusively single) with no sensitization to aeroallergens, called “AD with familial history of asthma”. Percentages of children suffering from asthma at the age of 6 were higher in clusters 2 and 3 (36.1% and 33.3% respectively versus 14.9% in cluster 1, p<0.01). Conclusion Two phenotypes in infants with early-onset AD convey a higher risk of developing asthma during childhood: multiple sensitization and familial history of asthma. PMID:26107938

  15. Clinical whole-genome sequencing in severe early-onset epilepsy reveals new genes and improves molecular diagnosis

    PubMed Central

    Martin, Hilary C.; Kim, Grace E.; Pagnamenta, Alistair T.; Murakami, Yoshiko; Carvill, Gemma L.; Meyer, Esther; Copley, Richard R.; Rimmer, Andrew; Barcia, Giulia; Fleming, Matthew R.; Kronengold, Jack; Brown, Maile R.; Hudspith, Karl A.; Broxholme, John; Kanapin, Alexander; Cazier, Jean-Baptiste; Kinoshita, Taroh; Nabbout, Rima; Bentley, David; McVean, Gil; Heavin, Sinéad; Zaiwalla, Zenobia; McShane, Tony; Mefford, Heather C.; Shears, Deborah; Stewart, Helen; Kurian, Manju A.; Scheffer, Ingrid E.; Blair, Edward; Donnelly, Peter; Kaczmarek, Leonard K.; Taylor, Jenny C.

    2014-01-01

    In severe early-onset epilepsy, precise clinical and molecular genetic diagnosis is complex, as many metabolic and electro-physiological processes have been implicated in disease causation. The clinical phenotypes share many features such as complex seizure types and developmental delay. Molecular diagnosis has historically been confined to sequential testing of candidate genes known to be associated with specific sub-phenotypes, but the diagnostic yield of this approach can be low. We conducted whole-genome sequencing (WGS) on six patients with severe early-onset epilepsy who had previously been refractory to molecular diagnosis, and their parents. Four of these patients had a clinical diagnosis of Ohtahara Syndrome (OS) and two patients had severe non-syndromic early-onset epilepsy (NSEOE). In two OS cases, we found de novo non-synonymous mutations in the genes KCNQ2 and SCN2A. In a third OS case, WGS revealed paternal isodisomy for chromosome 9, leading to identification of the causal homozygous missense variant in KCNT1, which produced a substantial increase in potassium channel current. The fourth OS patient had a recessive mutation in PIGQ that led to exon skipping and defective glycophosphatidyl inositol biosynthesis. The two patients with NSEOE had likely pathogenic de novo mutations in CBL and CSNK1G1, respectively. Mutations in these genes were not found among 500 additional individuals with epilepsy. This work reveals two novel genes for OS, KCNT1 and PIGQ. It also uncovers unexpected genetic mechanisms and emphasizes the power of WGS as a clinical tool for making molecular diagnoses, particularly for highly heterogeneous disorders. PMID:24463883

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

    PubMed

    Westra, Inge M; Oosterhuis, Dorenda; Groothuis, Geny M M; Olinga, Peter

    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 48h, viability was assessed by ATP and gene expression of PDGF-B and TGF-?1 and the fibrosis markers Hsp47, ?Sma 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, TGF?-pathway inhibitors, were determined. After 48h of incubation, viability of the PCLS was maintained and gene expression of PDGF-B was increased while TGF-?1 was not changed. Hsp47, ?Sma and Pcol1A1 gene expressions were significantly elevated in PCLS after 48h, which was further increased by PDGF-BB and TGF-?1. The increased gene expression of fibrosis markers was inhibited by all three PDGF-inhibitors, while TGF?-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-?1 gene expression and the limited effect of the TGF?-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. PMID:24321339

  17. Previously unrecognized missense mutation E126K of PSEN2 segregates with early onset Alzheimer's disease in a family.

    PubMed

    Müller, Ulrich; Winter, Pia; Bolender, Claus; Nolte, Dagmar

    2014-01-01

    Mutations in the gene PSEN2 are a rare cause of early onset Alzheimer's disease (EOAD). PSEN2 sequence variants are often only found in one patient and pathogenicity cannot be formally documented. Here we describe a previously unrecognized sequence change (c.376G>A) in PSEN2 in an EOAD patient and her likewise affected mother. This change results in the exchange of amino acid glutamic acid (E) by lysine (K) at position 126 of the protein (p.E126K). Pathogenicity of the mutation is shown by segregation with disease, evolutionary conservation of E126, and in silico analysis of the mutation. PMID:24844686

  18. Major myofibrillar changes in early onset myopathy due to de novo heterozygous missense mutation in lamin A/C gene.

    PubMed

    D'Amico, A; Benedetti, S; Petrini, S; Sambuughin, N; Boldrini, R; Menditto, I; Ferrari, M; Verardo, M; Goldfarb, L; Bertini, E

    2005-12-01

    Mutations in the lamin A/C gene (LMNA) have been associated with neuromuscular diseases and more complex syndromes, involving bone and adipose tissue. We report on a case of early onset myopathy due to a heterozygous LMNA mutation in exon 9, characterized by the presence of a marked number of cytoplasmic bodies with extensive myofibrillar abnormalities and Z-disk disruption in skeletal muscle. This case suggests there is a need to increase the list of genes to be screened in patients with myofibrillar myopathy. PMID:16288872

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

    SciTech Connect

    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-?1 and the fibrosis markers Hsp47, ?Sma 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, TGF?-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-?1 was not changed. Hsp47, ?Sma and Pcol1A1 gene expressions were significantly elevated in PCLS after 48 h, which was further increased by PDGF-BB and TGF-?1. The increased gene expression of fibrosis markers was inhibited by all three PDGF-inhibitors, while TGF?-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-?1 gene expression and the limited effect of the TGF?-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-? was increased, while TGF? was not changed in rat PCLS. • PDGF-pathway inhibitors down-regulated this increase of fibrosis markers. • TGF?-pathway inhibitors had only minor effects on fibrosis markers. • Rat PCLS can be used to study the early onset of fibrosis.

  20. Occlusal considerations in periodontics.

    PubMed

    Davies, S J; Gray, R J; Linden, G J; James, J A

    2001-12-01

    Periodontal disease does not directly affect the occluding surfaces of teeth, consequently some may find a section on periodontics a surprising inclusion. Trauma from the occlusion, however, has been linked with periodontal disease for many years. Karolyi published his pioneering paper, in 1901 'Beobachtungen uber Pyorrhoea alveolaris' (occlusal stress and 'alveolar pyorrhoea'). (1) However, despite extensive research over many decades, the role of occlusion in the aetiology and pathogenesis of inflammatory periodontitis is still not completely understood. PMID:11770945

  1. Reading aloud in Persian: ERP evidence for an early locus of the masked onset priming effect.

    PubMed

    Timmer, Kalinka; Vahid-Gharavi, Narges; Schiller, Niels O

    2012-07-01

    The current study investigates reading aloud words in Persian, a language that does not mark all its vowels in the script. Behaviorally, a masked onset priming effect (MOPE) was revealed for transparent words, with faster speech onset latencies in the phoneme-matching condition (i.e. phonological prime and target onset overlap; e.g. [symbol: see text] /s??l/; 'year' [symbol: see text] /sot/; 'voice') than the phoneme-mismatching condition (e.g. [symbol: see text] /t??b/ 'swing' - [symbol: see text] /sot/; 'voice'). For opaque target words (e.g. [symbol: see text] /solh/; 'peace'), no such effect was found. However, event-related potentials (ERPs) did reveal an amplitude difference between the two prime conditions in the 80-160 ms time window for transparent as well as opaque words. Only for the former, this effect continued into the 300-480 ms time window. This finding constrains the time course of the MOPE and suggests the simultaneous activation of both the non-lexical grapheme-to-phoneme and the lexical route in the dual-route cascaded (DRC) model. PMID:22632815

  2. Children of depressed parents. Increased psychopathology and early onset of major depression.

    PubMed

    Weissman, M M; Gammon, G D; John, K; Merikangas, K R; Warner, V; Prusoff, B A; Sholomskas, D

    1987-10-01

    Data on the psychiatric diagnosis, overall functioning, and treatment of 220 6- to 23-year-old subjects who were at high or low risk for major depression are presented. The subjects' diagnoses were made by a child psychiatrist based on best-estimate evaluation of diagnostic information derived from structured interviews (Schedule for Affective Disorders and Schizophrenia for School-Aged Children, Epidemiologic Version) with the subjects and separately with their mothers about their children. The major findings were an increased overall prevalence of major depression and substance abuse, psychiatric treatment, poor social functioning, and school problems in the children of depressed proband parents compared with children of normal proband parents. Overall prepubertal depression was uncommon and the sex ratios were equal. After 12 years of age, there was an increasing preponderance of female subjects in the group with major depression. The mean age at onset of major depression was similar for male and female subjects. However, it was significantly earlier in the children of depressed probands (mean age at onset, 12 to 13 years) compared with the children of normal probands (mean age at onset, 16 to 17 years). Symptom profiles and additional types of diagnoses in the depressed children from either proband parent group did not differ. These children are being followed up longitudinally to determine the prognostic significance, persistence, recurrence, and recall of their symptoms. Several research and clinical strategies are suggested by these data. PMID:3662741

  3. Early onset of primary hypogonadism revealed by serum anti-Müllerian hormone determination during infancy and childhood in trisomy 21.

    PubMed

    Grinspon, R P; Bedecarrás, P; Ballerini, M G; Iñiguez, G; Rocha, A; Mantovani Rodrigues Resende, E A; Brito, V N; Milani, C; Figueroa Gacitúa, V; Chiesa, A; Keselman, A; Gottlieb, S; Borges, M F; Ropelato, M G; Picard, J-Y; Codner, E; Rey, R A

    2011-10-01

    Male patients with an extra sex chromosome or autosome are expected to present primary hypogonadism at puberty owing to meiotic germ-cell failure. Scarce information is available on trisomy 21, a frequent autosomal aneuploidy. Our objective was to assess whether trisomy 21 presents with pubertal-onset, germ-cell specific, primary hypogonadism in males, or whether the hypogonadism is established earlier and affects other testicular cell populations. We assessed the functional status of the pituitary-testicular axis, especially Sertoli cell function, in 117 boys with trisomy 21 (ages: 2months-20year). To compare with an adequate control population, we established reference levels for serum anti-Müllerian hormone (AMH) in 421 normal males, from birth to adulthood, using a recently developed ultrasensitive assay. In trisomy 21, AMH was lower than normal, indicating Sertoli cell dysfunction, from early infancy, independently of the existence of cryptorchidism. The overall prevalence rate of AMH below the 3rd percentile was 64.3% in infants with trisomy 21. Follicle-stimulating hormone was elevated in patients <6months and after pubertal onset. Testosterone was within the normal range, but luteinizing hormone was elevated in most patients <6months and after pubertal onset, indicating a mild Leydig cell dysfunction. We conclude that in trisomy 21, primary hypogonadism involves a combined dysfunction of Sertoli and Leydig cells, which can be observed independently of cryptorchidism soon after birth, thus prompting the search for new hypotheses to explain the pathophysiology of gonadal dysfunction in autosomal trisomy. PMID:21831236

  4. Analysis of Dosage Mutation in PARK2 among Korean Patients with Early-Onset or Familial Parkinson's Disease

    PubMed Central

    Chu, Min Kyung; Kim, Won Chan; Choi, Jung Mi; Hong, Jeong-Hoon; Kang, Suk Yun; Ma, Hyeo-Il

    2014-01-01

    Background and Purpose There is some controversy regarding heterozygous mutations of the gene encoding parkin (PARK2) as risk factors for Parkinson's disease (PD), and all previous studies have been performed in non-Asian populations. Dosage mutation of PARK2, rather than a point mutation or small insertion/deletion mutation, was reported to be a risk factor for familial PD; dosage mutation of PARK2 is common in Asian populations. Methods We performed a gene-dosage analysis of PARK2 using real-time polymerase chain reaction for 189 patients with early-onset PD or familial PD, and 191 control individuals. In the case of PD patients with heterozygous gene-dosage mutation, we performed a sequencing analysis to exclude compound heterozygous mutations. The association between heterozygous mutation of PARK2 and PD was tested. Results We identified 22 PD patients with PARK2 mutations (11.6%). Five patients (2.6%) had compound heterozygous mutations, and 13 patients (6.9%) had a heterozygous mutation. The phase could not be determined in one patient. Three small sequence variations were found in 30 mutated alleles (10.0%). Gene-dosage mutation accounted for 90% of all of the mutations found. The frequency of a heterozygous PARK2 gene-dosage mutation was higher in PD patients than in the controls. Conclusions Heterozygous gene-dosage mutation of PARK2 is a genetic risk factor for patients with early-onset or familial PD in Koreans. PMID:25045378

  5. Artery tortuosity syndrome exhibiting early-onset emphysema with novel compound heterozygous SLC2A10 mutations.

    PubMed

    Takahashi, Yoshiko; Fujii, Katsunori; Yoshida, Akiko; Morisaki, Hiroko; Kohno, Yoichi; Morisaki, Takayuki

    2013-04-01

    We report on a 2-year-old Japanese boy with early-onset pulmonary emphysema, exhibiting dysmorphic face, loose skin, and inguinal and Morgagni hernias. He was admitted to our hospital owing to refractory respiratory infection. On the basis of his clinical features, we investigated the SLC2A10 gene and identified novel compound heterozygous mutations of c.417T > A and c.692G > A, leading to the diagnosis of artery tortuosity syndrome (ATS). This syndrome is an extremely rare autosomal recessive disorder characterized by tortuosity and elongation of the large and medium-sized arteries, hyperextensible skin, and diverse hernias, mostly reported from Europe and Middle Eastern countries, but not from Asia. Although chronic obstructive pulmonary disease, namely, emphysema, has not been well documented in ATS, it may be likely because TGF-beta up-regulation is known to be evoked by SLC2A10 mutations, resulting in reconstruction of pulmonary endothelial cells and emphysema. This is the first report of ATS associated with early-onset pulmonary emphysema, suggesting that patients with ATS may also require close attention for chronic obstructive pulmonary disease. PMID:23494979

  6. Co-Morbidity between Early-Onset Leukemia and Type 1 Diabetes – Suggestive of a Shared Viral Etiology?

    PubMed Central

    Hemminki, Kari; Houlston, Richard; Sundquist, Jan; Sundquist, Kristina; Shu, Xiaochen

    2012-01-01

    Background Acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) are common early-onset malignancies. Their causes are largely unknown but infectious etiology has been implicated. Type 1 diabetes (T1D) is an autoimmune disease for which infectious triggers of disease onset have been sought and increasing pointing to enteroviruses. Based on our previous results on co-morbidity between leukemia and T1D, we updated the Swedish dataset and focused on early onset leukemias in patients who had been hospitalized for T1D, comparing to those not hospitalized for T1D. Methods and Findings Standardized incidence ratios (SIRs) were calculated for leukemia in 24,052 patients hospitalized for T1D covering years 1964 through 2008. T1D patients were included if hospitalized before age 21 years. Practically all Swedish children and adolescents with T1D are hospitalized at the start of insulin treatment. SIR for ALL was 8.30 (N?=?18, 95% confidence interval 4.91–13.14) when diagnosed at age 10 to 20 years after hospitalization for T1D and it was 3.51 (13, 1.86–6.02) before hospitalization for T1D. The SIR for ALL was 19.85 (N?=?33, 13.74–27.76) and that for AML was 25.28 (8, 10.80–50.06) when the leukemias were diagnosed within the year of T1D hospitalization. The SIRs increased to 38.97 (26, 25.43–57.18) and 40.11 (8, 17.13–79.42) when T1D was diagnosed between ages 10 to 20 years. No consistent time-dependent changes were found in leukemia risk. Conclusion A shared infectious etiology could be a plausible explanation to the observed co-morbidity. Other possible contributing factors could be insulin therapy or T1D related metabolic disturbances. PMID:22745776

  7. Imitating actions on objects in early-onset and regressive autism: Effects and implications of task characteristics on performance

    PubMed Central

    Rogers, Sally J.; Young, Gregory S.; Cook, Ian; Giolzetti, Angelo; Ozonoff, Sally

    2010-01-01

    This study was designed to examine the nature of object imitation performance in early autism. We hypothesized that imitation would be relatively preserved when behaviors on objects resulted in salient instrumental effects. We designed tasks in which, in one condition, the motor action resulted in a salient, meaningful effect on an object, whereas in the other condition, the same action resulted in a less salient effect because of differing object characteristics. The motor aspects of the tasks did not vary across conditions. Four participant groups of 2- to 5-year-olds were examined: 17 children with early-onset autism, 24 children with regressive onset autism, 22 children with developmental delays, and 22 children with typical development. Groups were matched on nonverbal skills, and differences in verbal development were examined as a moderator of imitative ability. Results revealed an interaction of group by condition, with the combined autism group failing more tasks than the combined comparison groups, and failing more tasks in the less salient condition than in the more salient condition, as hypothesized. Analyses of autism subgroups revealed these effects were primarily because of the regression onset group. Accuracy of motor performance was examined by analyzing errors. Among children passing imitative acts, there were no group differences and no condition effects in the number, type, or pattern of performance errors. Among children passing the tasks, the group with autism did not demonstrate more emulation errors (imitating the goal but not the means) than other groups. There was no evidence that either motor or attentional aspects of the tasks contributed to the poorer imitative performance of the children with autism. PMID:20102648

  8. Impact of different periodontitis case definitions on periodontal research

    Microsoft Academic Search

    Alessandra N. Guimarães; Luís O. M. Cot

    2009-01-01

    Different periodontitis definitions have been used in periodontal research. This study assessed the impact of case definition on the prevalence and extent rates of periodontitis. A data set including 340 periodontal records, collected in Belo Horizonte, Brazil, was used. Periodontitis was defined as: 1) one site with probing depth (PD) ? 4 mm; 2) clinical attachment level (CAL) ? 5

  9. Diabetes and periodontitis

    PubMed Central

    Deshpande, Kalyani; Jain, Ashish; Sharma, RaviKant; Prashar, Savita; Jain, Rajni

    2010-01-01

    The main aim of this review is to update the reader with practical knowledge concerning the relationship between diabetes mellitus and periodontal diseases. Exclusive data is available on the association between these two chronic diseases till date. Articles published on this relationship often provide the knowledge of definitions of diabetes mellitus and periodontal diseases, prevalence, extent, severity of periodontal disease, complications of diabetes along with the possible underlying mechanisms. The authors reviewed human epidemiological studies, cross-sectional observations and longitudinal cohort, case control that evaluated variables exclusively over the past 30 years and the predominant findings from the “certain” articles are summarized in this review. This review clarifies certain queries such as 1) Do periodontal diseases have an effect on the metabolic control of diabetes? 2) Does diabetes act as a risk factor of periodontitis? 3) What are the possible underlying mechanisms relating the connection between these two chronic diseases? 4) What is the effect of periodontal intervention on metabolic control of diabetes? After a thorough survey of literature, it was observed that diabetes acts as a risk factor in development of periodontitis as periodontitis is significantly aggravated in patients suffering from diabetes having long term hyperglycemia. Different mechanisms underlying the association between the accelerated periodontal disease and diabetes are emerging but still more work is required. Major efforts are required to elucidate the impact of periodontal diseases on diabetes. At the same time, patients are needed to be made aware of regular periodontal maintenance schedule and oral hygiene. PMID:21731243

  10. Strategy to Accelerate or Augment the Antidepressant Response and for An Early Onset of SSRI Activity. Adjunctive Amisulpride to Fluvoxamine in Major Depressive Disorder

    PubMed Central

    Hardoy, Maria Carolina; Carta, Mauro Giovanni

    2010-01-01

    The topic of early response to antidepressant treatment has been extensively studied in major depressive disorder (MDD). We serendipitous observed an increase tolerability, a rapid response to therapy and an early onset of antidepressant fluvoxamine activity when associated with amisulpride in patients with major depressive disorder. The purpose of this study was to investigate our preliminary observations. PMID:20498696

  11. Periodontal Proteomics: Wonders Never Cease!

    PubMed Central

    Grover, Harpreet Singh; Kapoor, Shalini; Saksena, Neha

    2013-01-01

    Proteins are vital parts of living organisms, as they are integral components of the physiological metabolic pathways of cells. Periodontal tissues comprise multicompartmental groups of interacting cells and matrices that provide continuous support, attachment, proprioception, and physical protection for the teeth. The proteome map, that is, complete catalogue of the matrix and cellular proteins expressed in alveolar bone, cementum, periodontal ligament, and gingiva, is to be explored for more in-depth understanding of periodontium. The ongoing research to understand the signalling pathways that allow cells to divide, differentiate, and die in controlled manner has brought us to the era of proteomics. Proteomics is defined as the study of all proteins including their relative abundance, distribution, posttranslational modifications, functions, and interactions with other macromolecules, in a given cell or organism within a given environment and at a specific stage in the cell cycle. Its application to periodontal science can be used to monitor health status, disease onset, treatment response, and outcome. Proteomics can offer answers to critical, unresolved questions such as the biological basis for the heterogeneity in gingival, alveolar bone, and cemental cell populations. PMID:24490073

  12. Long-term outcomes of early-onset wheeze and asthma

    PubMed Central

    Grad, Roni; Morgan, Wayne J

    2012-01-01

    Evidence from longitudinal cohort studies demonstrates that wheezing which begins in early life and continues into the school age years generally persists into adulthood. This persistent wheezing is associated with lung function deficits and airways hyperresponsiveness that appear to be established in the first few years of life. Allergic sensitization early in life, early life infection with rhinovirus, or colonization with any of a number of bacteria have been associated with increased risk of persistent wheeze. Early life, whether in utero or in the first few years of life, presents a window of vulnerability during which airway injury results in persistent airways dysfunction. Available data futher suggest that a second such window of vulnerability may be present in the preadolescent and adolescent years. Lung function growth patterns established by age 6 generally continue into early to mid-adulthood, typically leaving groups of individuals with wheezing that persists into or relapses in adulthood with mean FEV1 about 10% predicted lower than their peers who do not wheeze. Subgroups of patients with persistent asthma, however, may have progressive declines in lung function, and enter adulthood with even lower lung function. The concern exists that these deficits in lung function apparent in early adulthood may put individuals at risk for the later development of chronic obstructive pulmonary disease. PMID:22738675

  13. Effects of early-onset voluntary exercise on adult physical activity and associated phenotypes in mice.

    PubMed

    Acosta, Wendy; Meek, Thomas H; Schutz, Heidi; Dlugosz, Elizabeth M; Vu, Kim T; Garland, Theodore

    2015-10-01

    The purpose of this study was to evaluate the effects of early-life exercise on adult physical activity (wheel running, home-cage activity), body mass, food consumption, and circulating leptin levels in males from four replicate lines of mice selectively bred for high voluntary wheel running (High Runner or HR) and their four non-selected control (C) lines. Half of the mice were given wheel access shortly after weaning for three consecutive weeks. Wheel access was then removed for 52 days, followed by two weeks of adult wheel access for all mice. A blood sample taken prior to adult wheel testing was analyzed for circulating leptin concentration. Early-life wheel access significantly increased adult voluntary exercise on wheels during the first week of the second period of wheel access, for both HR and C mice, and HR ran more than C mice. During this same time period, activity in the home cages was not affected by early-age wheel access, and did not differ statistically between HR and C mice. Throughout the study, all mice with early wheel access had lower body masses than their sedentary counterparts, and HR mice had lower body masses than C mice. With wheel access, HR mice also ate significantly more than C mice. Early-life wheel access increased plasma leptin levels (adjusted statistically for fat-pad mass as a covariate) in C mice, but decreased them in HR mice. At sacrifice, early-life exercise had no statistically significant effects on visceral fat pad, heart (ventricle), liver or spleen masses (all adjusted statistically for variation in body mass). Results support the hypothesis that early-age exercise in mice can have at least transitory positive effects on adult levels of voluntary exercise, in addition to reducing body mass, and may be relevant for the public policy debates concerning the importance of physical education for children. PMID:26079567

  14. IQCB1 and PDE6B Mutations Cause Similar Early Onset Retinal Degenerations in Two Closely Related Terrier Dog Breeds

    PubMed Central

    Goldstein, Orly; Mezey, Jason G.; Schweitzer, Peter A.; Boyko, Adam R.; Gao, Chuan; Bustamante, Carlos D.; Jordan, Julie Ann; Aguirre, Gustavo D.; Acland, Gregory M.

    2013-01-01

    Purpose. To identify the causative mutations in two early-onset canine retinal degenerations, crd1 and crd2, segregating in the American Staffordshire terrier and the Pit Bull Terrier breeds, respectively. Methods. Retinal morphology of crd1- and crd2-affected dogs was evaluated by light microscopy. DNA was extracted from affected and related unaffected controls. Association analysis was undertaken using the Illumina Canine SNP array and PLINK (crd1 study), or the Affymetrix Version 2 Canine array, the “MAGIC” genotype algorithm, and Fisher's Exact test for association (crd2 study). Positional candidate genes were evaluated for each disease. Results. Structural photoreceptor abnormalities were observed in crd1-affected dogs as young as 11-weeks old. Rod and cone inner segment (IS) and outer segments (OS) were abnormal in size, shape, and number. In crd2-affected dogs, rod and cone IS and OS were abnormal as early as 3 weeks of age, progressing with age to severe loss of the OS, and thinning of the outer nuclear layer (ONL) by 12 weeks of age. Genome-wide association study (GWAS) identified association at the telomeric end of CFA3 in crd1-affected dogs and on CFA33 in crd2-affected dogs. Candidate gene evaluation identified a three bases deletion in exon 21 of PDE6B in crd1-affected dogs, and a cytosine insertion in exon 10 of IQCB1 in crd2-affected dogs. Conclusions. Identification of the mutations responsible for these two early-onset retinal degenerations provides new large animal models for comparative disease studies and evaluation of potential therapeutic approaches for the homologous human diseases. PMID:24045995

  15. Early onset of neurological symptoms in fragile X premutation carriers exposed to neurotoxins.

    PubMed

    Paul, Ripon; Pessah, Isaac N; Gane, Louise; Ono, Michele; Hagerman, Paul J; Brunberg, James A; Tassone, Flora; Bourgeois, James A; Adams, Patrick E; Nguyen, Danh V; Hagerman, Randi

    2010-08-01

    We present four cases of fragile X premutation carriers with early neurological symptoms, including symptoms consistent with multiple sclerosis (MS) and fragile X-associated tremor/ataxia syndrome (FXTAS). Each patient had significant exposure to one or more environmental neurotoxicants that have documented neurotoxicity (i.e. hexachlorocyclopentadiene or C56, Agent Orange, and 2,4- or 2,6-toluene diisocyanate and dichlormate). We hypothesize that premutation carriers are a vulnerable group to neurotoxins because elevated mRNA in the premutation can lead to early cell death and brain disease, leading to neuropsychiatric and neurological symptoms consistent with FXTAS. PMID:20466021

  16. Early onset of neurological symptoms in fragile X premutation carriers exposed to neurotoxins

    PubMed Central

    Paul, Ripon; Pessah, Isaac N.; Gane, Louise; Ono, Michele; Hagerman, Paul J.; Brunberg, James A.; Tassone, Flora; Bourgeois, James A.; Adams, Patrick E.; Nguyen, Danh V.; Hagerman, Randi

    2014-01-01

    We present four cases of fragile X premutation carriers with early neurological symptoms, including symptoms consistent with multiple sclerosis (MS) and fragile X-associated tremor/ataxia syndrome (FXTAS). Each patient had significant exposure to one or more environmental neurotoxicants that have documented neurotoxicity (i.e. hexachlorocyclopentadiene or C56, Agent Orange, and 2,4- or 2,6-toluene diisocyanate and dichlormate). We hypothesize that premutation carriers are a vulnerable group to neurotoxins because elevated mRNA in the premutation can lead to early cell death and brain disease, leading to neuropsychiatric and neurological symptoms consistent with FXTAS. PMID:20466021

  17. The Lambeth Early Onset (LEO) Team: randomised controlled trial of the effectiveness of specialised care for early psychosis

    Microsoft Academic Search

    Tom K J Craig; Philippa Garety; Paddy Power; Nikola Rahaman; Susannah Colbert; Miriam Fornells-Ambrojo; Graham Dunn

    2004-01-01

    Objective To evaluate the effectiveness of a service for early psychosis. Design Randomised controlled clinical trial. Setting Community mental health teams in one London borough. Participants 144 people aged 16-40 years presenting to mental health services for the first or second time with non-organic, non-affective psychosis. Interventions Assertive outreach with evidence based biopsychosocial interventions (specialised care group) and standard care

  18. Apolipoprotein E genotype and neuropathological phenotype in two members of a German family with chromosome 14-linked early onset Alzheimer's disease

    Microsoft Academic Search

    R. Egensperger; S. Kösel; R. Schnabel; P. Mehraein; M. B. Graeber

    1995-01-01

    Molecular genetic analysis was performed in two autopsy-confirmed cases of early-onset Alzheimer's disease belonging to a large German pedigree [FAD2, according to the nomenclature of St. George-Hyslop, et al. (1987) Science 235:885–890]. The disease in this family has been linked to chromosome 14. As gene interactions are considered to influence the age of onset and tissue pathology in Alzheimer's disease,

  19. Multiple endocrine neoplasia 2B syndrome due to codon 918 mutation: clinical manifestation and course in early and late onset disease.

    PubMed

    Brauckhoff, Michael; Gimm, Oliver; Weiss, Carl-Ludwig; Ukkat, Jörg; Sekulla, Carsten; Brauckhoff, Katrin; Thanh, Phuong Nguyen; Dralle, Henning

    2004-12-01

    More than 50% of patients with typical MEN-2B have a de novo M918T germline mutation of the RET protooncogene. However, even in typical MEN-2B, extrathyroidal manifestations of MEN-2B can be found to be differently expressed. We analyzed the clinical manifestation and course in 21 patients harboring a de novo RET M918T mutation. Mean age at MEN-2B diagnosis was 14.2 years (range: 1-31 years). All patients had medullary thyroid carcinoma (MTC). At the time of syndrome diagnosis, oral manifestations (bumpy lips, ganglioneuroma), ocular manifestations (corneal fibers, conjunctivitis sicca), intestinal dysfunctions, musculoskeletal manifestations, and pheochromocytoma were found in 86%, 90%, 74%, 79%, and 19% of the patients, respectively. At the time of follow-up examination, the symptoms were found at higher frequency. Severe intestinal manifestation was predominantly found in patients with prepubertal onset (< or = 12 years) of MTC (n = 4/10) compared with patients with late onset (> 12 years) of MTC (n = 0/11) (40% versus 0%; p = 0.019). Although biochemical cure was found only in four patients with early onset of MTC, the long-term prognosis for patients with early onset of MTC was poorer than for patients presenting with late onset of MTC (p = 0.005). During mean follow-up of 55.8 months (range: 3-161 months), seven patients (33%) died from MTC. In conclusion, whereas most typical MEN-2B symptoms were found to be age-related, severe intestinal manifestation was found to be predominantly expressed in patients with early onset of MTC. Furthermore, in patients with early onset of MTC who could not be biochemically cured, the long-term prognosis was found to be worse than that of non-cured patients with late onset of MTC, suggesting an additional pathological process in the younger subgroup reinforcing the very high transforming in vitro activity of the M918T RET mutation. PMID:15517484

  20. Caveats and truths in genetic, clinical, autoimmune and autoinflammatory issues in Blau syndrome and early onset sarcoidosis.

    PubMed

    Caso, Francesco; Costa, Luisa; Rigante, Donato; Vitale, Antonio; Cimaz, Rolando; Lucherini, Orso Maria; Sfriso, Paolo; Verrecchia, Elena; Tognon, Sofia; Bascherini, Vittoria; Galeazzi, Mauro; Punzi, Leonardo; Cantarini, Luca

    2014-12-01

    Blau syndrome (BS) and early onset sarcoidosis (EOS) are, respectively, the familial and sporadic forms of the pediatric granulomatous autoinflammatory disease, which belong to the group of monogenic autoinflammatory syndromes. Both of these conditions are caused by mutations in the NOD2 gene, which encodes the cytosolic NOD2 protein, one of the pivotal molecules in the regulation of innate immunity, primarily expressed in the antigen-presenting cells. Clinical onset of BS and EOS is usually in the first years of life with noncaseating epithelioid granulomas mainly affecting joints, skin, and uveal tract, variably associated with heterogeneous systemic features. The dividing line between autoinflammatory and autoimmune mechanisms is probably not so clear-cut, and the relationship existing between BS or EOS and autoimmune phenomena remains unclear. There is no established therapy for the management of BS and EOS, and the main treatment aim is to prevent ocular manifestations entailing the risk of potential blindness and to avoid joint deformities. Nonsteroidal anti-inflammatory drugs, corticosteroids and immunosuppressive drugs, such as methotrexate or azathioprine, may be helpful; when patients are unresponsive to the combination of corticosteroids and immunosuppressant agents, the tumor necrosis factor-? inhibitor infliximab should be considered. Data on anti-interleukin-1 inhibition with anakinra and canakinumab is still limited and further corroboration is required. The aim of this paper is to describe BS and EOS, focusing on their genetic, clinical, and therapeutic issues, with the ultimate goal of increasing clinicians' awareness of both of these rare but serious disorders. PMID:25182201

  1. A Functional Mutation in the Terminal Exon of Elastin in Severe, Early-Onset Chronic Obstructive Pulmonary Disease

    PubMed Central

    Kelleher, Cassandra M.; Silverman, Edwin K.; Broekelmann, Thomas; Litonjua, Augusto A.; Hernandez, Melvin; Sylvia, Jody S.; Stoler, Joan; Reilly, John J.; Chapman, Harold A.; Speizer, Frank E.; Weiss, Scott T.; Mecham, Robert P.; Raby, Benjamin A.

    2005-01-01

    We describe a novel variant in the terminal exon of human elastin, c.2318 G>A, resulting in an amino acid substitution of glycine 773 to aspartate (G773D) in a pedigree with severe early-onset chronic obstructive pulmonary disease (COPD). Transfection studies with elastin cDNAs demonstrate that the glycine to aspartate change compromises the ability of the mutant protein to undergo normal elastin assembly. Other functional consequences of this amino acid substitution include altered proteolytic susceptibility of the C-terminal region of elastin and reduced interaction of the exon 36 sequence with matrix receptors on cells. These results suggest that the G773D variant confers structural and functional consequences relevant to the pathogenesis of COPD. PMID:16081882

  2. Early-onset metabolic syndrome in mice lacking the intestinal uric acid transporter SLC2A9

    PubMed Central

    DeBosch, Brian J.; Kluth, Oliver; Fujiwara, Hideji; Schürmann, Annette; Moley, Kelle

    2015-01-01

    Excess circulating uric acid, a product of hepatic glycolysis and purine metabolism, often accompanies metabolic syndrome. However, whether hyperuricemia contributes to development of metabolic syndrome or is merely a by-product of other processes that cause this disorder has not been resolved. Additionally, how uric acid is cleared from the circulation is incompletely understood. Here, we present a genetic model of spontaneous, early-onset metabolic syndrome in mice lacking the enterocyte urate transporter Glut9 (encoded by the SLC2A9 gene). Glut9-deficient mice develop impaired enterocyte uric acid transport kinetics, hyperuricemia, hyperuricosuria, spontaneous hypertension, dyslipidemia, and elevated body fat. Allopurinol, a xanthine oxidase inhibitor, can reverse the hypertension and hypercholesterolemia. These data provide evidence that hyperuricemia per se could have deleterious metabolic sequelae. Moreover, these findings suggest that enterocytes may regulate whole-body metabolism, and that enterocyte urate metabolism could potentially be targeted to modulate or prevent metabolic syndrome. PMID:25100214

  3. Novel ANKH amino terminus mutation (Pro5Ser) associated with early-onset calcium pyrophosphate disease with associated phosphaturia.

    PubMed

    Gruber, Barry L; Couto, Ana Rita; Armas, Jácome Bruges; Brown, Matthew A; Finzel, Kathleen; Terkeltaub, Robert A

    2012-06-01

    This report describes a 32-year-old woman presenting since childhood with progressive calcium pyrophosphate disease (CPPD), characterized by severe arthropathy and chondrocalcinosis involving multiple peripheral joints and intervertebral disks. Because ANKH mutations have been previously described in familial CPPD, the proband's DNA was assessed at this locus by direct sequencing of promoter and coding regions and revealed 3 sequence variants in ANKH. Sequences of exon 1 revealed a novel isolated nonsynonymous mutation (c.13 C>T), altering amino acid in codon 5 from proline to serine (CCG>TCG). Sequencing of parental DNA revealed an identical mutation in the proband's father but not the mother. Subsequent clinical evaluation demonstrated extensive chondrocalcinosis and degenerative arthropathy in the proband's father. In summary, we report a novel mutation, not previously described, in ANKH exon 1, wherein serine replaces proline, in a case of early-onset severe CPPD associated with metabolic abnormalities, with similar findings in the proband's father. PMID:22647861

  4. Gait Analysis in a Mecp2 Knockout Mouse Model of Rett Syndrome Reveals Early-Onset and Progressive Motor Deficits

    PubMed Central

    Riddell, John S.; Bailey, Mark E. S.; Cobb, Stuart R.

    2014-01-01

    Rett syndrome (RTT) is a genetic disorder characterized by a range of features including cognitive impairment, gait abnormalities and a reduction in purposeful hand skills. Mice harbouring knockout mutations in the Mecp2 gene display many RTT-like characteristics and are central to efforts to find novel therapies for the disorder. As hand stereotypies and gait abnormalities constitute major diagnostic criteria in RTT, it is clear that motor and gait-related phenotypes will be of importance in assessing preclinical therapeutic outcomes. We therefore aimed to assess gait properties over the prodromal phase in a functional knockout mouse model of RTT. In male Mecp2 knockout mice, we observed alterations in stride, coordination and balance parameters at 4 weeks of age, before the onset of other overt phenotypic changes as revealed by observational scoring. These data suggest that gait measures may be used as a robust and early marker of MeCP2-dysfunction in future preclinical therapeutic studies. PMID:25392929

  5. Mutation in NDUFA13/GRIM19 leads to early onset hypotonia, dyskinesia and sensorial deficiencies, and mitochondrial complex I instability.

    PubMed

    Angebault, Claire; Charif, Majida; Guegen, Naig; Piro-Megy, Camille; Mousson de Camaret, Benedicte; Procaccio, Vincent; Guichet, Pierre-Olivier; Hebrard, Maxime; Manes, Gael; Leboucq, Nicolas; Rivier, François; Hamel, Christian P; Lenaers, Guy; Roubertie, Agathe

    2015-07-15

    Mitochondrial complex I (CI) deficiencies are causing debilitating neurological diseases, among which, the Leber Hereditary Optic Neuropathy and Leigh Syndrome are the most frequent. Here, we describe the first germinal pathogenic mutation in the NDUFA13/GRIM19 gene encoding a CI subunit, in two sisters with early onset hypotonia, dyskinesia and sensorial deficiencies, including a severe optic neuropathy. Biochemical analysis revealed a drastic decrease in CI enzymatic activity in patient muscle biopsies, and reduction of CI-driven respiration in fibroblasts, while the activities of complex II, III and IV were hardly affected. Western blots disclosed that the abundances of NDUFA13 protein, CI holoenzyme and super complexes were drastically reduced in mitochondrial fractions, a situation that was reproduced by silencing NDUFA13 in control cells. Thus, we established here a correlation between the first mutation yet identified in the NDUFA13 gene, which induces CI instability and a severe but slowly evolving clinical presentation affecting the central nervous system. PMID:25901006

  6. Early-Onset Conduct Problems: Intersection of Conduct Problems and Poverty

    PubMed Central

    Shaw, Daniel S.; Shelleby, Elizabeth C.

    2014-01-01

    The current paper reviewed extant literature on the intersection between poverty and the development of conduct problems (CP) in early childhood. Associations between exposure to poverty and disruptive behavior were reviewed through the framework of models emphasizing how the stressors associated with poverty indirectly influence child CP by compromising parent psychological resources, investments in children’s welfare, and/or caregiving quality. We expanded upon the most well studied of these models, the family stress model, by emphasizing the mediating contribution of parent psychological resources on children’s risk for early CP, in addition to the mediating effects of parenting. Specifically, in we focused on the contribution of maternal depression, both in terms of compromising parenting quality and exposing children to even higher levels of stressful events and contexts. Implications of the adapted family stress model were then discussed in terms of its implications for the prevention and treatment of young children’s emerging CP. PMID:24471370

  7. A pilot genome-wide association study of early-onset breast cancer

    Microsoft Academic Search

    Muhammad G. Kibriya; Farzana Jasmine; Maria Argos; Irene L. Andrulis; Esther M. John; Jenny Chang-Claude; Habibul Ahsan

    2009-01-01

    High-density oligonucleotide microarrays containing a large number of single nucleotide polymorphisms (SNPs) have enabled\\u000a genome-wide association (GWA) analysis to become a reality. We used the early access Affymetrix Mendel Nsp 250K chips in a\\u000a GWA case–control pilot study to identify genomic regions associated with breast cancer. We included 30 randomly sampled incident\\u000a invasive breast cancer cases aged <45 years without deleterious

  8. Characterization of the MODY3 phenotype. Early-onset diabetes caused by an insulin secretion defect.

    PubMed Central

    Lehto, M; Tuomi, T; Mahtani, M M; Widén, E; Forsblom, C; Sarelin, L; Gullström, M; Isomaa, B; Lehtovirta, M; Hyrkkö, A; Kanninen, T; Orho, M; Manley, S; Turner, R C; Brettin, T; Kirby, A; Thomas, J; Duyk, G; Lander, E; Taskinen, M R; Groop, L

    1997-01-01

    Maturity-onset diabetes of the young (MODY) type 3 is a dominantly inherited form of diabetes, which is often misdiagnosed as non-insulin-dependent diabetes mellitus (NIDDM) or insulin-dependent diabetes mellitus (IDDM). Phenotypic analysis of members from four large Finnish MODY3 kindreds (linked to chromosome 12q with a maximum lod score of 15) revealed a severe impairment in insulin secretion, which was present also in those normoglycemic family members who had inherited the MODY3 gene. In contrast to patients with NIDDM, MODY3 patients did not show any features of the insulin resistance syndrome. They could be discriminated from patients with IDDM by lack of glutamic acid decarboxylase antibodies (GAD-Ab). Taken together with our recent findings of linkage between this region on chromosome 12 and an insulin-deficient form of NIDDM (NIDDM2), the data suggest that mutations at the MODY3/NIDDM2 gene(s) result in a reduced insulin secretory response, that subsequently progresses to diabetes and underlines the importance of subphenotypic classification in studies of diabetes. PMID:9045858

  9. Clinical and neuropathological features of the Arctic APP mutation causing early onset Alzheimer's disease

    PubMed Central

    Basun, Hans; Bogdanovic, Nenad; Ingelsson, Martin; Almkvist, Ove; Näslund, Jan; Axelman, Karin; Bird, Thomas D.; Nochlin, David; Schellenberg, Gerard D.; Wahlund, Lars-Olof; Lannfelt, Lars

    2009-01-01

    Background A majority of mutations within the amyloid ? (A?) region of the amyloid precursor protein (APP) gene cause inherited forms of intracerebral haemorrhage. Most of these mutations may also cause cognitive impairment, but the Arctic APP mutation is the only known intra-A? mutation to date causing the more typical clinical picture of Alzheimer's disease (AD). Objective To describe features of one Swedish and one American family with the previously reported Arctic APP mutation. Subjects Affected and non-affected carriers of the Arctic APP mutation from the Swedish and American families were investigated clinically. In addition, one brain from each family was investigated neuropathologically. Results The clinical picture, with age at disease onset in the sixth to seventh decade of life and dysfunction in multiple cognitive areas, is indicative of AD and similar to the phenotype for other AD APP mutations. Several affected mutation carriers displayed general brain atrophy and reduced blood flow of the parietal lobe, as demonstrated by magnetic resonance imaging and single photon emission computed tomography. One Swedish and one American case with the Arctic APP mutation have come to autopsy, neither of which showed any signs of haemorrhage but revealed severe congophilic angiopathy, region-specific neurofibrillary tangle pathology as well as abundant amyloid plaques. Intriguingly, a majority of plaques from both of these cases had a characteristic ring-like character. Conclusions Overall, our findings corroborate that the Arctic APP mutation causes a clinical and neuropathological picture compatible with AD. PMID:18413473

  10. Onset of the DNA Replication Checkpoint in the Early Drosophila Embryo

    PubMed Central

    Crest, Justin; Oxnard, Nathan; Ji, Jun-Yuan; Schubiger, Gerold

    2007-01-01

    The Drosophila embryo is a promising model for isolating gene products that coordinate S phase and mitosis. We have reported before that increasing maternal Cyclin B dosage to up to six copies (six cycB) increases Cdk1–Cyclin B (CycB) levels and activity in the embryo, delays nuclear migration at cycle 10, and produces abnormal nuclei at cycle 14. Here we show that the level of CycB in the embryo inversely correlates with the ability to lengthen interphase as the embryo transits from preblastoderm to blastoderm stages and defines the onset of a checkpoint that regulates mitosis when DNA replication is blocked with aphidicolin. A screen for modifiers of the six cycB phenotypes identified 10 new suppressor deficiencies. In addition, heterozygote dRPA2 (a DNA replication gene) mutants suppressed only the abnormal nuclear phenotype at cycle 14. Reduction of dRPA2 also restored interphase duration and checkpoint efficacy to control levels. We propose that lowered dRPA2 levels activate Grp/Chk1 to counteract excess Cdk1–CycB activity and restore interphase duration and the ability to block mitosis in response to aphidicolin. Our results suggest an antagonistic interaction between DNA replication checkpoint activation and Cdk1–CycB activity during the transition from preblastoderm to blastoderm cycles. PMID:17151243

  11. Mutations in RAB39B Cause X-Linked Intellectual Disability and Early-Onset Parkinson Disease with ?-Synuclein Pathology

    PubMed Central

    Wilson, Gabrielle R.; Sim, Joe C.H.; McLean, Catriona; Giannandrea, Maila; Galea, Charles A.; Riseley, Jessica R.; Stephenson, Sarah E.M.; Fitzpatrick, Elizabeth; Haas, Stefan A.; Pope, Kate; Hogan, Kirk J.; Gregg, Ronald G.; Bromhead, Catherine J.; Wargowski, David S.; Lawrence, Christopher H.; James, Paul A.; Churchyard, Andrew; Gao, Yujing; Phelan, Dean G.; Gillies, Greta; Salce, Nicholas; Stanford, Lynn; Marsh, Ashley P.L.; Mignogna, Maria L.; Hayflick, Susan J.; Leventer, Richard J.; Delatycki, Martin B.; Mellick, George D.; Kalscheuer, Vera M.; D’Adamo, Patrizia; Bahlo, Melanie; Amor, David J.; Lockhart, Paul J.

    2014-01-01

    Advances in understanding the etiology of Parkinson disease have been driven by the identification of causative mutations in families. Genetic analysis of an Australian family with three males displaying clinical features of early-onset parkinsonism and intellectual disability identified a ?45 kb deletion resulting in the complete loss of RAB39B. We subsequently identified a missense mutation (c.503C>A [p.Thr168Lys]) in RAB39B in an unrelated Wisconsin kindred affected by a similar clinical phenotype. In silico and in vitro studies demonstrated that the mutation destabilized the protein, consistent with loss of function. In vitro small-hairpin-RNA-mediated knockdown of Rab39b resulted in a reduction in the density of ?-synuclein immunoreactive puncta in dendritic processes of cultured neurons. In addition, in multiple cell models, we demonstrated that knockdown of Rab39b was associated with reduced steady-state levels of ?-synuclein. Post mortem studies demonstrated that loss of RAB39B resulted in pathologically confirmed Parkinson disease. There was extensive dopaminergic neuron loss in the substantia nigra and widespread classic Lewy body pathology. Additional pathological features included cortical Lewy bodies, brain iron accumulation, tau immunoreactivity, and axonal spheroids. Overall, we have shown that loss-of-function mutations in RAB39B cause intellectual disability and pathologically confirmed early-onset Parkinson disease. The loss of RAB39B results in dysregulation of ?-synuclein homeostasis and a spectrum of neuropathological features that implicate RAB39B in the pathogenesis of Parkinson disease and potentially other neurodegenerative disorders. PMID:25434005

  12. Mutations in RAB39B cause X-linked intellectual disability and early-onset Parkinson disease with ?-synuclein pathology.

    PubMed

    Wilson, Gabrielle R; Sim, Joe C H; McLean, Catriona; Giannandrea, Maila; Galea, Charles A; Riseley, Jessica R; Stephenson, Sarah E M; Fitzpatrick, Elizabeth; Haas, Stefan A; Pope, Kate; Hogan, Kirk J; Gregg, Ronald G; Bromhead, Catherine J; Wargowski, David S; Lawrence, Christopher H; James, Paul A; Churchyard, Andrew; Gao, Yujing; Phelan, Dean G; Gillies, Greta; Salce, Nicholas; Stanford, Lynn; Marsh, Ashley P L; Mignogna, Maria L; Hayflick, Susan J; Leventer, Richard J; Delatycki, Martin B; Mellick, George D; Kalscheuer, Vera M; D'Adamo, Patrizia; Bahlo, Melanie; Amor, David J; Lockhart, Paul J

    2014-12-01

    Advances in understanding the etiology of Parkinson disease have been driven by the identification of causative mutations in families. Genetic analysis of an Australian family with three males displaying clinical features of early-onset parkinsonism and intellectual disability identified a ?45 kb deletion resulting in the complete loss of RAB39B. We subsequently identified a missense mutation (c.503C>A [p.Thr168Lys]) in RAB39B in an unrelated Wisconsin kindred affected by a similar clinical phenotype. In silico and in vitro studies demonstrated that the mutation destabilized the protein, consistent with loss of function. In vitro small-hairpin-RNA-mediated knockdown of Rab39b resulted in a reduction in the density of ?-synuclein immunoreactive puncta in dendritic processes of cultured neurons. In addition, in multiple cell models, we demonstrated that knockdown of Rab39b was associated with reduced steady-state levels of ?-synuclein. Post mortem studies demonstrated that loss of RAB39B resulted in pathologically confirmed Parkinson disease. There was extensive dopaminergic neuron loss in the substantia nigra and widespread classic Lewy body pathology. Additional pathological features included cortical Lewy bodies, brain iron accumulation, tau immunoreactivity, and axonal spheroids. Overall, we have shown that loss-of-function mutations in RAB39B cause intellectual disability and pathologically confirmed early-onset Parkinson disease. The loss of RAB39B results in dysregulation of ?-synuclein homeostasis and a spectrum of neuropathological features that implicate RAB39B in the pathogenesis of Parkinson disease and potentially other neurodegenerative disorders. PMID:25434005

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

    PubMed

    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. PMID:22277901

  14. A Novel Point Mutation in the KCNJ5 Gene Causing Primary Hyperaldosteronism and Early-Onset Autosomal Dominant Hypertension

    PubMed Central

    Sertedaki, Amalia; Kino, Tomoshige; Merakou, Christina; Hoffman, Dax A.; Hatch, Michael M.; Hurt, Darrell E.; Lin, Lin; Xekouki, Paraskevi; Stratakis, Constantine A.; Chrousos, George P.

    2012-01-01

    Context: Aldosterone production in the adrenal zona glomerulosa is mainly regulated by angiotensin II, [K+], and ACTH. Genetic deletion of subunits of K+-selective leak (KCNK) channels TWIK-related acid sensitive K+-1 and/or TWIK-related acid sensitive K+-3 in mice results in primary hyperaldosteronism, whereas mutations in the KCNJ5 (potassium inwardly rectifying channel, subfamily J, member 5) gene are implicated in primary hyperaldosteronism and, in certain cases, in autonomous glomerulosa cell proliferation in humans. Objective: The objective of the study was to investigate the role of KCNK3, KCNK5, KCNK9, and KCNJ5 genes in a family with primary hyperaldosteronism and early-onset hypertension. Patients and Methods: Two patients, a mother and a daughter, presented with severe primary hyperaldosteronism, bilateral massive adrenal hyperplasia, and early-onset hypertension refractory to medical treatment. Genomic DNA was isolated and the exons of the entire coding regions of the above genes were amplified and sequenced. Electrophysiological studies were performed to determine the effect of identified mutation(s) on the membrane reversal potentials. Results: Sequencing of the KCNJ5 gene revealed a single, heterozygous guanine to thymine (G ? T) substitution at nucleotide position 470 (n.G470T), resulting in isoleucine (I) to serine (S) substitution at amino acid 157 (p.I157S). This mutation results in loss of ion selectivity, cell membrane depolarization, increased Ca2+ entry in adrenal glomerulosa cells, and increased aldosterone synthesis. Sequencing of the KCNK3, KCNK5, and KCNK9 genes revealed no mutations in our patients. Conclusions: These findings explain the pathogenesis in a subset of patients with severe hypertension and implicate loss of K+ channel selectivity in constitutive aldosterone production. PMID:22628607

  15. Early-onset obesity and paternal 2pter deletion encompassing the ACP1, TMEM18, and MYT1L genes

    PubMed Central

    Doco-Fenzy, Martine; Leroy, Camille; Schneider, Anouck; Petit, Florence; Delrue, Marie-Ange; Andrieux, Joris; Perrin-Sabourin, Laurence; Landais, Emilie; Aboura, Azzedine; Puechberty, Jacques; Girard, Manon; Tournaire, Magali; Sanchez, Elodie; Rooryck, Caroline; Ameil, Agnès; Goossens, Michel; Jonveaux, Philippe; Lefort, Geneviève; Taine, Laurence; Cailley, Dorothée; Gaillard, Dominique; Leheup, Bruno; Sarda, Pierre; Geneviève, David

    2014-01-01

    Obesity is a common but highly, clinically, and genetically heterogeneous disease. Deletion of the terminal region of the short arm of chromosome 2 is rare and has been reported in about 13 patients in the literature often associated with a Prader–Willi-like phenotype. We report on five unrelated patients with 2p25 deletion of paternal origin presenting with early-onset obesity, hyperphagia, intellectual deficiency, and behavioural difficulties. Among these patients, three had de novo pure 2pter deletions, one presented with a paternal derivative der(2)t(2;15)(p25.3;q26) with deletion in the 2pter region and the last patient presented with an interstitial 2p25 deletion. The size of the deletions was characterized by SNP array or array-CGH and was confirmed by fluorescence in situ hybridization (FISH) studies. Four patients shared a 2p25.3 deletion with a minimal critical region estimated at 1.97?Mb and encompassing seven genes, namely SH3HYL1, ACP1, TMEMI8, SNTG2, TPO, PXDN, and MYT1L genes. The fifth patient had a smaller interstitial deletion encompassing the TPO, PXDN, and MYT1L genes. Paternal origin of the deletion was determined by genotyping using microsatellite markers. Analysis of the genes encompassed in the deleted region led us to speculate that the ACP1, TMEM18, and/or MYT1L genes might be involved in early-onset obesity. In addition, intellectual deficiency and behavioural troubles can be explained by the heterozygous loss of the SNTG2 and MYT1L genes. Finally, we discuss the parent-of-origin of the deletion. PMID:24129437

  16. Postweaning Exposure to Dietary Zearalenone, a Mycotoxin, Promotes Premature Onset of Puberty and Disrupts Early Pregnancy Events in Female Mice

    PubMed Central

    Ye, Xiaoqin

    2013-01-01

    Zearalenone (ZEA) is a mycotoxin commonly found in contaminated livestock feed and human food with levels in the range of ppb and low ppm. It was hypothesized that ZEA, an endocrine disruptor, could affect puberty and early pregnancy. To test this hypothesis, newly weaned (3 weeks old) C57BL/6J female mice were exposed to 0, 0.002, 4, 10, and 40 ppm ZEA and 0.05 ppm diethylstilbestrol (positive control) in phytoestrogen-free AIN-93G diet. Females exposed to 10 and 40 ppm ZEA diets showed earlier onset of vaginal opening. Those treated with 40 ppm ZEA diet also had earlier first copulation plug and irregular estrous cyclicity. At 8 weeks old, all females were mated with untreated stud males on AIN-93G diet during mating. Treatment resumed upon identification of a vaginal plug on gestation day 0.5 (D0.5). Embryo implantation was assessed on D4.5. Exposure to 40 ppm ZEA diet resulted in reduced percentage of plugged mice with implantation sites, distended uterine appearance, and retained expression of progesterone receptor in D4.5 uterine epithelium. To determine the exposure timing and mechanisms of disrupted embryo implantation, four groups of females were fed with 0 or 40 ppm ZEA diets during premating (weaning to mating) and postmating (D0.5–D4.5), respectively. Premating exposure to 40 ppm ZEA diet reduced fertilization rate, whereas postmating exposure to 40 ppm ZEA diet delayed embryo transport and preimplantation embryo development, which subsequently affected embryo implantation. These data demonstrate that postweaning exposure to dietary ZEA can promote premature onset of puberty and disrupt early pregnancy events. PMID:23291560

  17. Caring for early-onset dementia with excessive wandering of over 30 kilometres per day: a case report.

    PubMed

    Yamakawa, Miyae; Yoshida, Yukiko; Higami, Yoko; Shigenobu, Kazue; Makimoto, Kiyoko

    2014-12-01

    Excessive wandering in people in dementia is associated with a severe care burden. However, the quantification of excessive wandering has not been described, and its cause and treatment have not been evaluated with objective measurements to date. The purpose of this study was to evaluate pharmacological treatments and non-pharmacological interventions to reduce excessive wandering in an early-onset Alzheimer disease patient with objective indicators. Wandering was quantified using an integrated circuit monitoring system that measured the distance moved and the location of the patient. Monitoring was conducted in the dementia ward of a general hospital in 2012. Sleep quality was measured by non-wear actigraphy. The study was approved by the ethics committees of the Osaka University School of Allied Health Science, and of the study hospital. The case involved a 62-year-old woman diagnosed with early-onset Alzheimer disease and hospitalized in 2012 because of irritability and agitation; her Mini-Mental State Examination score was 5/30 and her Clinical Dementia Rating score was 3. When olanzapine (2.5?mg) was prescribed, she developed insomnia, and her wandering movements increased from 10 to 20?km/day. On some days, it exceeded 30?km/day, and she walked most of the night. She did not experience weight loss or physical exhaustion, but she sustained a minor injury in her left sole. Olanzapine was increased to 7.5?mg, but these problems persisted. Nursing staff discovered triggers for wandering and insomnia, including high sensitivity to odour and noise in the living room or her room. When the environment was changed to meet her needs, the distance moved per day decreased to <15?km and the sleep disturbances disappeared. This case demonstrated the difficulty in assessing the degree of ambulation and sleep disorder. Objective indicators are essential in evaluating the effectiveness of pharmacological and non-pharmacological interventions. PMID:25369874

  18. Role of Innate Host Defenses in Susceptibility to Early Onset Neonatal Sepsis

    PubMed Central

    Wynn, James L.; Levy, Ofer

    2010-01-01

    Neonatal sepsis continues to take a devastating toll globally. Although adequate to protect against invasive infection in most newborns, the distinct function of neonatal innate host defense coupled with impairments in adaptive immune responses, increases the likelihood of acquiring infection early in life with subsequent rapid dissemination and death. Unique differences exist between neonates and older populations with respect to the capacity, quantity, and quality of innate host responses to pathogens. Recent characterization of the age-dependent maturation of neonatal innate immune function has identified novel translational approaches that may lead to improved diagnostic, prophylactic and therapeutic modalities. PMID:20569810

  19. Role of innate host defenses in susceptibility to early-onset neonatal sepsis.

    PubMed

    Wynn, James L; Levy, Ofer

    2010-06-01

    Neonatal sepsis continues to take a devastating toll globally. Although adequate to protect against invasive infection in most newborns, the distinct function of neonatal innate host defense coupled with impairments in adaptive immune responses increases the likelihood of acquiring infection early in life, with subsequent rapid dissemination and death. Unique differences exist between neonates and older populations with respect to the capacity, quantity, and quality of innate host responses to pathogens. Recent characterization of the age-dependent maturation of neonatal innate immune function has identified novel translational approaches that may lead to improved diagnostic, prophylactic, and therapeutic modalities. PMID:20569810

  20. An Increased Osteoprotegerin Serum Release Characterizes the Early Onset of Diabetes Mellitus and May Contribute to Endothelial Cell Dysfunction

    PubMed Central

    Secchiero, Paola; Corallini, Federica; Pandolfi, Assunta; Consoli, Agostino; Candido, Riccardo; Fabris, Bruno; Celeghini, Claudio; Capitani, Silvano; Zauli, Giorgio

    2006-01-01

    Serum osteoprotegerin (OPG) is significantly increased in diabetic patients, prompting expanded investigation of the correlation between OPG production/release and glycemic levels. Serum levels of OPG, but not of its cognate ligand receptor activator of nuclear factor-?B ligand (RANKL), were significantly increased in type 2 diabetes mellitus patients compared with healthy blood donors. Serum OPG was also significantly elevated in a subgroup of recently diagnosed diabetic patients (within 2 years). The relationship between serum OPG and diabetes mellitus onset was next investigated in apoE-null and littermate mice. Serum OPG increased early after diabetes induction in both mouse strains and showed a positive correlation with blood glucose levels and an inverse correlation with the levels of free (OPG-unbound) RANKL. The in vitro addition of tumor necrosis factor-? to human vascular endothelial cells, but not human peripheral blood mononuclear cells, markedly enhanced OPG release in culture. In contrast, high glucose concentrations did not modulate OPG release when used alone or in association with tumor necrosis factor-?. Moreover, the ability of soluble RANKL to activate the extracellular signal-regulated kinase/mitogen-activated protein kinase and endothelial nitric-oxide synthase pathways in endothelial cells was neutralized by preincubation with recombinant OPG. Altogether, these findings suggest that increased OPG production represents an early event in the natural history of diabetes mellitus, possibly contributing to disease-associated endothelial cell dysfunction. PMID:17148684

  1. PNPLA2 mutation: a paediatric case with early onset but indolent course.

    PubMed

    Perrin, Laurine; Féasson, Léonard; Furby, Alain; Laforêt, Pascal; Petit, François M; Gautheron, Vincent; Chabrier, Stéphane

    2013-12-01

    Neutral lipid storage disease (NLSD) due to PNPLA2 mutation is a rare disorder with a severe muscular and cardiac outcome. All but one reported cases have been diagnosed during adulthood. It is thus ordinarily distinguished from Chanarin-Dorfman syndrome, a paediatric NLSD with a more widespread symptomatology. We report the case of a young child incidentally diagnosed with significant and persistent hyperCKemia. At 3 years, muscle biopsy showed marked lipid storage. A homozygous mutation in PNPLA2 was found. Fourteen years later, the noticeable outcome is the absence of muscle weakness at rest, a normal muscular MRI, and no cardiac involvement. Yet the patient exhibits some systemic features, notably hearing loss. This paediatric case of NLSD with myopathy indicates that important lipid accumulation may occur very early in the absence of patent clinical and imaging muscle involvement. Furthermore, PNPLA2 mutations may be associated with multisystem features more frequently encountered in Chanarin-Dorfman syndrome. PMID:24074500

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

    PubMed Central

    de Graaf, Ron; Radovanovic, Mirjana; van Laar, Margriet; Fairman, Brian; Degenhardt, Louisa; Aguilar-Gaxiola, Sergio; Bruffaerts, Ronny; de Girolamo, Giovanni; Fayyad, John; Gureje, Oye; Haro, Josep Maria; Huang, Yueqin; Kostychenko, Stanislav; Lépine, Jean-Pierre; Matschinger, Herbert; Mora, Maria Elena Medina; Neumark, Yehuda; Ormel, Johan; Posada-Villa, Jose; Stein, Dan J.; Tachimori, Hisateru; Wells, J. Elisabeth; Anthony, James C.

    2010-01-01

    Early-onset cannabis use is widespread in many countries and might cause later onset of depression. Sound epidemiologic data across countries are missing. The authors estimated the suspected causal association that links early-onset (age <17 years) cannabis use with later-onset (age ?17 years) risk of a depression spell, using data on 85,088 subjects from 17 countries participating in the population-based World Health Organization World Mental Health Survey Initiative (2001–2005). In all surveys, multistage household probability samples were evaluated with a fully structured diagnostic interview for assessment of psychiatric conditions. The association between early-onset cannabis use and later risk of a depression spell was studied using conditional logistic regression with local area matching of cases and controls, controlling for sex, age, tobacco use, and other mental health problems. The overall association was modest (controlled for sex and age, risk ratio = 1.5, 95% confidence interval: 1.4, 1.7), was statistically robust in 5 countries, and showed no sex difference. The association did not change appreciably with statistical adjustment for mental health problems, except for childhood conduct problems, which reduced the association to nonsignificance. This study did not allow differentiation of levels of cannabis use; this issue deserves consideration in future research. PMID:20534820

  3. Loss of Raf-1 Kinase Inhibitory Protein Delays Early-Onset Severe Retinal Ciliopathy in Cep290rd16 Mouse

    PubMed Central

    Subramanian, Balajikarthick; Anand, Manisha; Khan, Naheed W.; Khanna, Hemant

    2014-01-01

    Purpose. Mutations in the cilia-centrosomal protein of centrosomal protein of 290 kDa (CEP290) result in severe ciliopathies, including autosomal recessive early onset childhood blindness disorder Leber congenital amaurosis (LCA). The Cep290rd16 (retinal degeneration 16) mouse model of CEP290-LCA exhibits accumulation of CEP290-interacting protein Raf-1 kinase inhibitory protein (RKIP) prior to onset of retinal degeneration (by postnatal day P14). We hypothesized that reducing RKIP levels in the Cep290rd16 mouse will delay or improve retinal phenotype. Methods. We generated double mutant mice by combining the Cep290rd16 and Rkipko alleles (Cep290rd16:Rkip+/ko and Cep290rd16:Rkipko/ko). Retinal function was assessed by ERG and retinal morphology and protein trafficking were assessed by histology, transmission electron microscopy (TEM), and immunofluorescence analysis. Cell death was examined by apoptosis. Results. Prior to testing our hypothesis, we examined ERG and retinal morphology of Rkipko/ko mice and did not find any detectable differences compared with wild-type mice. The Cep290rd16:Rkip+/ko mice exhibited similar retinopathy as Cep290rd16; however, Cep290rd16: Rkipko/ko double knockout mice demonstrated a substantial improvement (>9-fold) in photoreceptor function and structure at P18 as of Cep290rd16 mice. We consistently detected transient preservation of photoreceptors at P18 and polarized trafficking of opsins to sensory cilia in the double mutant mice; however, retinal degeneration ensued by P30. Conclusions. Our studies implicate CEP290-RKIP pathway in CEP290-retinal degeneration and suggest that targeting RKIP levels can delay photoreceptor degeneration, assisting in extending the time-window for treating such rapidly progressing blindness disorder. PMID:25125607

  4. The Psychosis Recent Onset GRoningen Survey (PROGR-S): defining dimensions and improving outcomes in early psychosis.

    PubMed

    Liemburg, Edith J; Castelein, Stynke; van Es, Frank; Scholte-Stalenhoef, Anne Neeltje; van de Willige, Gerard; Smid, Henderikus; Visser, Ellen; Knegtering, Henderikus; Bruggeman, Richard

    2014-01-01

    Psychotic disorders are among the most complex medical conditions. Longitudinal cohort studies may offer further insight into determinants of functional outcome after a psychotic episode. This paper describes the Psychosis Recent Onset in GRoningen Survey (PROGR-S) that currently contains data on 1076 early-episode patients with psychosis, including symptoms, personality, cognition, life events and other outcome determinants. Our goal in this report is to give an overview of PROGR-S, as a point of reference for future publications on the effect of cognition, personality and psychosocial functioning on outcomes. PROGR-S contains an extensive, diagnostic battery including anamnesis, biography, socio-demographic characteristics, clinical status, drug use, neuropsychological assessment, personality questionnaires, and physical status tests. Extensive follow-up data is available on psychopathology, physical condition, medication use, and care consumption. Sample characteristics were determined and related to existing literature. PROGR-S (period 1997-2009, n = 718) included the majority of the expected referrals in the catchment area. The average age was 27 (SD = 8.6) and two-thirds were male. The average IQ was lower than that in the healthy control group. The majority had been diagnosed with a psychotic spectrum disorder. A substantial number of the patients had depressive symptoms (479/718, 78%) and current cannabis or alcohol use (465/718, 75%). The level of community functioning was moderate, i.e. most patients were not in a relationship and were unemployed. The PROGR-S database contains a valuable cohort to study a range of aspects related to symptomatic and functional outcomes of recent onset psychosis, which may play a role in the treatment of this complex and disabling disorder. Results reported here show interesting starting points for future research. Thus, we aim to investigate long-term outcomes on the basis of cognition, personality, negative symptoms and physical health. Ultimately, we hope that this paper will contribute improving the health of patients with psychotic disorders. PMID:25412332

  5. Community Structure Analysis of Transcriptional Networks Reveals Distinct Molecular Pathways for Early- and Late-Onset Temporal Lobe Epilepsy with Childhood Febrile Seizures

    PubMed Central

    Moreira-Filho, Carlos Alberto; Bando, Silvia Yumi; Bertonha, Fernanda Bernardi; Iamashita, Priscila; Silva, Filipi Nascimento; Costa, Luciano da Fontoura; Silva, Alexandre Valotta; Castro, Luiz Henrique Martins; Wen, Hung-Tzu

    2015-01-01

    Age at epilepsy onset has a broad impact on brain plasticity and epilepsy pathomechanisms. Prolonged febrile seizures in early childhood (FS) constitute an initial precipitating insult (IPI) commonly associated with mesial temporal lobe epilepsy (MTLE). FS-MTLE patients may have early disease onset, i.e. just after the IPI, in early childhood, or late-onset, ranging from mid-adolescence to early adult life. The mechanisms governing early (E) or late (L) disease onset are largely unknown. In order to unveil the molecular pathways underlying E and L subtypes of FS-MTLE we investigated global gene expression in hippocampal CA3 explants of FS-MTLE patients submitted to hippocampectomy. Gene coexpression networks (GCNs) were obtained for the E and L patient groups. A network-based approach for GCN analysis was employed allowing: i) the visualization and analysis of differentially expressed (DE) and complete (CO) - all valid GO annotated transcripts - GCNs for the E and L groups; ii) the study of interactions between all the system’s constituents based on community detection and coarse-grained community structure methods. We found that the E-DE communities with strongest connection weights harbor highly connected genes mainly related to neural excitability and febrile seizures, whereas in L-DE communities these genes are not only involved in network excitability but also playing roles in other epilepsy-related processes. Inversely, in E-CO the strongly connected communities are related to compensatory pathways (seizure inhibition, neuronal survival and responses to stress conditions) while in L-CO these communities harbor several genes related to pro-epileptic effects, seizure-related mechanisms and vulnerability to epilepsy. These results fit the concept, based on fMRI and behavioral studies, that early onset epilepsies, although impacting more severely the hippocampus, are associated to compensatory mechanisms, while in late MTLE development the brain is less able to generate adaptive mechanisms, what has implications for epilepsy management and drug discovery. PMID:26011637

  6. Infrasound of lava fountains at Etna (Italy): implications for early warning eruption onset

    NASA Astrophysics Data System (ADS)

    Ripepe, M.; Ulivieri, G.; Marchetti, E.

    2012-04-01

    Volcano ash-eruptions produce devastating consequences for local communities and the air transport. Here we present the results of the real-time monitoring of the 2011-2012 sequences of lava fountains eruptions at Etna volcano (Italy) by means of small-aperture (250 m) infrasonic array located at 5 km of distance from the active vents. Most of the episodes generated sustained ash columns up to 10 km height with significant fallout of lapilli and ash up to 30 km of distance from summit craters causing problems at the Fontanarossa airport. The infrasonic activity before lava fountain episodes shows a clear acoustic trend and a distinctive waveform and frequency content of the recorded signals, reflecting the ongoing increasing of explosive level. Infrasound reveals that lava fountains are characterized by a sustained, low frequency, oscillations that are preceded by a violent and rhythmic strombolian activity. These characteristics allow the definition of infrasonic-based thresholds, which could be used as early warning system. The infrasonic array at Etna revealed to be a robust and efficient monitoring tool for real-time alert also in hostile weather conditions.

  7. Early-onset autoimmune disease as a manifestation of primary immunodeficiency.

    PubMed

    Carneiro-Sampaio, Magda; Coutinho, Antonio

    2015-01-01

    Autoimmune disorders (AID) have been increasingly observed in association with primary immunodeficiencies (PIDs). Here, we discuss the interface between PID and AID, focusing on autoimmune manifestations early in life, which can be diagnostic clues for underlying PIDs. Inflammatory bowel disease in infants and children has been associated with IL-10 and IL-10R deficiencies, chronic granulomatous disease, immunedysregulation-polyendocrinopathy-enteropathy-X-linked syndrome (IPEX), autoinflammatory disorders, and others. Some PIDs have been identified as underlying defects in juvenile systemic lupus erythematosus: C1q-, IgA-, IgM deficiencies, alterations of the IFN-? pathway (in Aicardi-Goutières syndrome due to TREX1 mutation). IPEX (due to FOXP3 mutation leading to Treg cell deficiency), usually appearing in the first months of life, was recently observed in miscarried fetuses with hydrops who presented with CD3+ infiltrating lymphocytes in the pancreas. Hemophagocytic lymphohistiocytosis due to perforin deficiency was also identified as a cause of fetal hydrops. In conclusion, PID should be suspected in any infant with signs of autoimmunity after excluding transferred maternal effects, or in children with multiple and/or severe AID. PMID:25999944

  8. Chicken embryos as a potential new model for early onset type I diabetes.

    PubMed

    Shi, Liheng; Ko, Michael L; Huang, Cathy Chia-Yu; Park, So-Young; Hong, Min-Pyo; Wu, Chaodong; Ko, Gladys Y-P

    2014-01-01

    Diabetic retinopathy (DR) is the leading cause of blindness among the American working population. The purpose of this study is to establish a new diabetic animal model using a cone-dominant avian species to address the distorted color vision and altered cone pathway responses in prediabetic and early diabetic patients. Chicken embryos were injected with either streptozotocin (STZ), high concentration of glucose (high-glucose), or vehicle at embryonic day 11. Cataracts occurred in varying degrees in both STZ- and high glucose-induced diabetic chick embryos at E18. Streptozotocin-diabetic chicken embryos had decreased levels of blood insulin, glucose transporter 4 (Glut4), and phosphorylated protein kinase B (pAKT). In STZ-injected E20 embryos, the ERG amplitudes of both a- and b-waves were significantly decreased, the implicit time of the a-wave was delayed, while that of the b-wave was significantly increased. Photoreceptors cultured from STZ-injected E18 embryos had a significant decrease in L-type voltage-gated calcium channel (L-VGCC) currents, which was reflected in the decreased level of L-VGCC?1D subunit in the STZ-diabetic retinas. Through these independent lines of evidence, STZ-injection was able to induce pathological conditions in the chicken embryonic retina, and it is promising to use chickens as a potential new animal model for type I diabetes. PMID:25133191

  9. Early-Onset Autoimmune Disease as a Manifestation of Primary Immunodeficiency

    PubMed Central

    Carneiro-Sampaio, Magda; Coutinho, Antonio

    2015-01-01

    Autoimmune disorders (AID) have been increasingly observed in association with primary immunodeficiencies (PIDs). Here, we discuss the interface between PID and AID, focusing on autoimmune manifestations early in life, which can be diagnostic clues for underlying PIDs. Inflammatory bowel disease in infants and children has been associated with IL-10 and IL-10R deficiencies, chronic granulomatous disease, immunedysregulation-polyendocrinopathy-enteropathy-X-linked syndrome (IPEX), autoinflammatory disorders, and others. Some PIDs have been identified as underlying defects in juvenile systemic lupus erythematosus: C1q-, IgA-, IgM deficiencies, alterations of the IFN-? pathway (in Aicardi–Goutières syndrome due to TREX1 mutation). IPEX (due to FOXP3 mutation leading to Treg cell deficiency), usually appearing in the first months of life, was recently observed in miscarried fetuses with hydrops who presented with CD3+ infiltrating lymphocytes in the pancreas. Hemophagocytic lymphohistiocytosis due to perforin deficiency was also identified as a cause of fetal hydrops. In conclusion, PID should be suspected in any infant with signs of autoimmunity after excluding transferred maternal effects, or in children with multiple and/or severe AID. PMID:25999944

  10. Early-onset cortico-cortical synchronization in the hemiparkinsonian rat model.

    PubMed

    Jávor-Duray, B N; Vinck, M; van der Roest, M; Mulder, A B; Stam, C J; Berendse, H W; Voorn, P

    2015-02-01

    Changes in synchronized neuronal oscillatory activity are reported in both cortex and basal ganglia of Parkinson's disease patients. The origin of these changes, in particular their relationship with the progressive nigrostriatal dopaminergic denervation, is unknown. Therefore, in the present study we studied interregional neuronal synchronization in motor cortex and basal ganglia during the development of dopaminergic degeneration induced by a unilateral infusion of 6-hydroxydopamine (6-OHDA) into the rat medial forebrain bundle. We performed serial local field potential recordings bilaterally in the motor cortex and the subthalamic nucleus of the lesioned hemisphere prior to, during, and after development of the nigrostriatal dopaminergic cell loss. We obtained signal from freely moving rats in both resting and walking conditions, and we computed local spectral power, interregional synchronization (using phase lag index), and directionality (using Granger causality). After neurotoxin injection the first change in phase lag index was an increment in cortico-cortical synchronization. We observed increased bidirectional Granger causality in the beta frequency band between cortex and subthalamic nucleus within the lesioned hemisphere. In the walking condition, the 6-OHDA lesion-induced changes in synchronization resembled that of the resting state, whereas the changes in Granger causality were less pronounced after the lesion. Considering the relatively preserved connectivity pattern of the cortex contralateral to the lesioned side and the early emergence of increased cortico-cortical synchronization during development of the 6-OHDA lesion, we suggest a putative compensatory role of cortico-cortical coupling. PMID:25392174

  11. Comparison of the Psychological Symptoms and Disease-Specific Quality of Life between Early- and Typical-Onset Parkinson's Disease Patients

    PubMed Central

    Hadizadeh, Hasti; Farhadi, Farzaneh; Delbari, Ahmad; Lökk, Johan

    2014-01-01

    The impact of Parkinson's disease (PD) on psychological status and quality of life (QoL) may vary depending on age of disease onset. The aim of this study was to compare psychological symptoms and disease-specific QoL between early onset versus the rest of the PD patients. A total number of 140 PD patients with the mean current age of 61.3 (SD = 10.4)?yr were recruited in this study. PD patients with the onset age of ?50?yr were defined as “early-onset” (EOPD) group (n = 45), while the ones with >50?yr at the time of diagnosis were categorized as the “typical-onset” (TOPD) patients (n = 95). Different questionnaires and scales were used for between-group comparisons including PDQ39, HADS (hospital anxiety and depression scale), FSS (fatigue severity scale), MNA (mininutritional assessment), and the UPDRS. Depression score was significantly higher in EOPD group (6.3 (SD = 4.5) versus 4.5 (SD = 4.2), P = 0.02). Among different domains of QoL, emotion score was also significantly higher in the EOPD group (32.3 (SD = 21.6) versus 24.4 (SD = 22.7), P = 0.05). Our findings showed more severe depression and more impaired emotional domain of QoL in early-onset PD patients. Depression and anxiety play an important role to worsen QoL among both EOPD and TOPD patients, while no interaction was observed in the efficacy of these two psychiatric symptoms and the onset age of PD patients. PMID:25614849

  12. Comparison of the Psychological Symptoms and Disease-Specific Quality of Life between Early- and Typical-Onset Parkinson's Disease Patients.

    PubMed

    Fereshtehnejad, Seyed-Mohammad; Hadizadeh, Hasti; Farhadi, Farzaneh; Shahidi, Gholam Ali; Delbari, Ahmad; Lökk, Johan

    2014-01-01

    The impact of Parkinson's disease (PD) on psychological status and quality of life (QoL) may vary depending on age of disease onset. The aim of this study was to compare psychological symptoms and disease-specific QoL between early onset versus the rest of the PD patients. A total number of 140 PD patients with the mean current age of 61.3 (SD = 10.4)?yr were recruited in this study. PD patients with the onset age of ?50?yr were defined as "early-onset" (EOPD) group (n = 45), while the ones with >50?yr at the time of diagnosis were categorized as the "typical-onset" (TOPD) patients (n = 95). Different questionnaires and scales were used for between-group comparisons including PDQ39, HADS (hospital anxiety and depression scale), FSS (fatigue severity scale), MNA (mininutritional assessment), and the UPDRS. Depression score was significantly higher in EOPD group (6.3 (SD = 4.5) versus 4.5 (SD = 4.2), P = 0.02). Among different domains of QoL, emotion score was also significantly higher in the EOPD group (32.3 (SD = 21.6) versus 24.4 (SD = 22.7), P = 0.05). Our findings showed more severe depression and more impaired emotional domain of QoL in early-onset PD patients. Depression and anxiety play an important role to worsen QoL among both EOPD and TOPD patients, while no interaction was observed in the efficacy of these two psychiatric symptoms and the onset age of PD patients. PMID:25614849

  13. Periodontitis associated with osteomalacia.

    PubMed

    Wankhede, Anand Narayanrao; Sayed, Arshad Jamal; Gattani, Deepti Rakesh; Bhutada, Girish Parashram

    2014-09-01

    Osteomalacia is a metabolic bone disorder characterized by an alternation of bone mineralization, bone pain, increased bone fragility and fractures. A 23-year-old female patient reported with short stature and depressed nasal bridge with oral manifestation showing partial anodontia and periodontitis. This case report attempt to highlights clinical, radiographic, biochemical features of osteomalacia and periodontitis. PMID:25425827

  14. Microbial dysbiosis in periodontitis

    PubMed Central

    Nath, Sameera G.; Raveendran, Ranjith

    2013-01-01

    Periodontitis is a biofilm-associated inflammatory disease of the periodontium. This disease appears to have multiple etiologies with microbial factor contributing to initiation of the disease and immunological factor of the host propagating the disease. This review is on the concept of “microbial dysbiosis” and molecular nature of periodontitis, and the scope of traditional and emerging technologies for treating this disease. PMID:24174742

  15. Complement and periodontitis.

    PubMed

    Hajishengallis, George

    2010-12-15

    Although the complement system is centrally involved in host defense, its overactivation or deregulation (e.g., due to inherent host genetic defects or due to pathogen subversion) may excessively amplify inflammation and contribute to immunopathology. Periodontitis is an oral infection-driven chronic inflammatory disease which exerts a systemic impact on health. This paper reviews evidence linking complement to periodontal inflammation and pathogenesis. Clinical and histological observations show a correlation between periodontal inflammatory activity and local complement activation. Certain genetic polymorphisms or deficiencies in specific complement components appear to predispose to increased susceptibility to periodontitis. Animal model studies and in vitro experiments indicate that periodontal bacteria can either inhibit or activate distinct components of the complement cascade. Porphyromonas gingivalis, a keystone species in periodontitis, subverts complement receptor 3 and C5a anaphylatoxin receptor signaling in ways that promote its adaptive fitness in the presence of non-productive inflammation. Overall, available evidence suggests that complement activation or subversion contributes to periodontal pathogenesis, although not all complement pathways or functions are necessarily destructive. Effective complement-targeted therapeutic intervention in periodontitis would require determining the precise roles of the various inductive or effector complement pathways. This information is essential as it may reveal which specific pathways need to be blocked to counteract microbial evasion and inflammatory pathology or, conversely, kept intact to promote host immunity. PMID:20599785

  16. Hypersexual Behavior in Frontotemporal Dementia: A Comparison with Early-Onset Alzheimer’s Disease

    PubMed Central

    Mendez, Mario F.; Shapira, Jill S.

    2013-01-01

    The basis of hypersexual behavior among patients with dementia is not entirely clear. Hypersexual behavior may be a particular feature of behavioral variant frontotemporal dementia (bvFTD), which affects ventromedial frontal and adjacent anterior temporal regions specialized in interpersonal behavior. Recent efforts to define Hypersexual Disorder indicate an increasing awareness of heightened sexual activity as a source of personal distress and functional impairment, and clarification of hypersexuality in bvFTD could contribute to understanding the neurobiology of this behavior. This study reviewed 47 patients with bvFTD compared to 58 patients with Alzheimer’s disease (AD) for the presence of heightened sexual activity to the point of distress to caregivers and others. Hypersexual behavior occurred in 6 (13%) bvFTD patients compared to none of the AD patients. Caregivers judged all six bvFTD patients with hypersexual behavior as having a dramatic increase in sexual frequency from premorbid levels. All had general disinhibition, poor impulse control, and actively sought sexual stimulation. They had widened sexual interests and experienced sexual arousal from previously unexciting stimuli. One patient, with early and predominant right anterior temporal involvement, was easily aroused by slight stimuli, such as touching her palms. Although previously considered to be predominantly disinhibited sexual behavior as part of generalized disinhibition, these patients with dementia illustrate varying degrees of increased sexual desire. We conclude that bvFTD is uniquely associated with hypersexuality; it is more than just cognitive impairment with frontal disinhibition but also involves alterations in sexual drive, possibly from right anterior temporal-limbic involvement in this disease. PMID:23297146

  17. Rising incidence of early-onset colorectal cancer in Australia over two decades: report and review.

    PubMed

    Young, Joanne P; Win, Aung Ko; Rosty, Christophe; Flight, Ingrid; Roder, David; Young, Graeme P; Frank, Oliver; Suthers, Graeme K; Hewett, Peter J; Ruszkiewicz, Andrew; Hauben, Ehud; Adelstein, Barbara-Ann; Parry, Susan; Townsend, Amanda; Hardingham, Jennifer E; Price, Timothy J

    2015-01-01

    The average age at diagnosis for colorectal cancer (CRC) in Australia is 69, and the age-specific incidence rises rapidly after age 50 years. The incidence has stabilized or is declining in older age groups in Australia during recent decades, possibly related to the increased uptake of screening and high-risk surveillance. In the same time frame, a rising incidence of CRC in younger adults has been well-documented in the United States. This rise in incidence in the young has not been reported from other countries that share long-term exposure to westernised urban lifestyles. Using data from the Australian Institute of Health and Welfare, we examined trends in national incidence rates for CRC under age 50 years and observed that rates in people under age 40 years have been rising for the last two decades. We further performed a review of the literature regarding CRC in young adults to outline the extent of current understanding, explore potential risk factors such as obesity, alcohol, and sedentary lifestyles, and to identify the questions remaining to be addressed. Although absolute numbers might not justify a population screening approach, the dispersal of young adults with CRC across the primary health-care system decreases probability of their recognition. Patient and physician awareness, aided by stool and emerging blood-screening tests and risk profiling tools, have the potential to aid in identification of those young adults who would most benefit from a colonoscopy through early detection of CRCs or by removal of advanced polyps. PMID:25251195

  18. Inflammatory cues acting on the adult intestinal stem cells and the early onset of cancer (Review)

    PubMed Central

    DE LERMA BARBARO, A.; PERLETTI, G.; BONAPACE, I.M.; MONTI, E.

    2014-01-01

    The observation that cancer often arises at sites of chronic inflammation has prompted the idea that carcinogenesis and inflammation are deeply interwoven. In fact, the current literature highlights a role for chronic inflammation in virtually all the steps of carcinogenesis, including tumor initiation, promotion and progression. The aim of the present article is to review the current literature on the involvement of chronic inflammation in the initiation step and in the very early phases of tumorigenesis, in a type of cancer where adult stem cells are assumed to be the cells of origin of neoplasia. Since the gastrointestinal tract is regarded as the best-established model system to address the liaison between chronic inflammation and neoplasia, the focus of this article will be on intestinal cancer. In fact, the anatomy of the intestinal epithelial lining is uniquely suited to study adult stem cells in their niche, and the bowel crypt is an ideal developmental biology system, as proliferation, differentiation and cell migration are all distributed linearly along the long axis of the crypt. Moreover, crypt stem cells are regarded today as the most likely targets of neoplastic transformation in bowel cancer. More specifically, the present review addresses the molecular mechanisms whereby a state of chronic inflammation could trigger the neoplastic process in the intestine, focusing on the generation of inflammatory cues evoking enhanced proliferation in cells not initiated but at risk of neoplastic transformation because of their stemness. Novel experimental approaches, based on triggering an inflammatory stimulus in the neighbourhood of adult intestinal stem cells, are warranted to address some as yet unanswered questions. A possible approach, the targeted transgenesis of Paneth cells, may be aimed at ‘hijacking’ the crypt stem cell niche from a status characterized by the maintenance of homeostasis to local chronic inflammation, with the prospect of initiating neoplastic transformation in that site. PMID:24920319

  19. Dietary regimens modify early onset of obesity in mice haploinsufficient for Rai1.

    PubMed

    Alaimo, Joseph T; Hahn, Natalie H; Mullegama, Sureni V; Elsea, Sarah H

    2014-01-01

    Smith-Magenis syndrome is a complex genomic disorder in which a majority of individuals are obese by adolescence. While an interstitial deletion of chromosome 17p11.2 is the leading cause, mutation or deletion of the RAI1 gene alone results in most features of the disorder. Previous studies have shown that heterozygous knockout of Rai1 results in an obese phenotype in mice and that Smith-Magenis syndrome mouse models have a significantly reduced fecundity and an altered transmission pattern of the mutant Rai1 allele, complicating large, extended studies in these models. In this study, we show that breeding C57Bl/6J Rai1+/- mice with FVB/NJ to create F1 Rai1+/- offspring in a mixed genetic background ameliorates both fecundity and Rai1 allele transmission phenotypes. These findings suggest that the mixed background provides a more robust platform for breeding and larger phenotypic studies. We also characterized the effect of dietary intake on Rai1+/- mouse growth during adolescent and early adulthood developmental stages. Animals fed a high carbohydrate or a high fat diet gained weight at a significantly faster rate than their wild type littermates. Both high fat and high carbohydrate fed Rai1+/- mice also had an increase in body fat and altered fat distribution patterns. Interestingly, Rai1+/- mice fed different diets did not display altered fasting blood glucose levels. These results suggest that dietary regimens are extremely important for individuals with Smith-Magenis syndrome and that food high in fat and carbohydrates may exacerbate obesity outcomes. PMID:25127133

  20. Hypersexual behavior in frontotemporal dementia: a comparison with early-onset Alzheimer's disease.

    PubMed

    Mendez, Mario F; Shapira, Jill S

    2013-04-01

    The basis of hypersexual behavior among patients with dementia is not entirely clear. Hypersexual behavior may be a particular feature of behavioral variant frontotemporal dementia (bvFTD), which affects ventromedial frontal and adjacent anterior temporal regions specialized in interpersonal behavior. Recent efforts to define hypersexual disorder indicate an increasing awareness of heightened sexual activity as a source of personal distress and functional impairment, and clarification of hypersexuality in bvFTD could contribute to understanding the neurobiology of this behavior. This study reviewed 47 patients with bvFTD compared to 58 patients with Alzheimer's disease (AD) for the presence of heightened sexual activity to the point of distress to caregivers and others. Hypersexual behavior occurred in 6 (13 %) bvFTD patients compared to none of the AD patients. Caregivers judged all six bvFTD patients with hypersexual behavior as having a dramatic increase in sexual frequency from premorbid levels. All had general disinhibition, poor impulse control, and actively sought sexual stimulation. They had widened sexual interests and experienced sexual arousal from previously unexciting stimuli. One patient, with early and predominant right anterior temporal involvement, was easily aroused by slight stimuli, such as touching her palms. Although previously considered to be predominantly disinhibited sexual behavior as part of generalized disinhibition, these patients with dementia illustrate varying degrees of increased sexual desire. We conclude that bvFTD is uniquely associated with hypersexuality; it is more than just cognitive impairment with frontal disinhibition but also involves alterations in sexual drive, possibly from right anterior temporal- limbic involvement in this disease. PMID:23297146

  1. "Distressed aging": the differences in brain activity between early-and late-onset Jae-Jin Song a,*, Dirk De Ridder b,c

    E-print Network

    O'Toole, Alice J.

    "Distressed aging": the differences in brain activity between early- and late-onset tinnitus Jae Accepted 17 January 2013 Available online 15 February 2013 Keywords: Tinnitus Aging Electroencephalography a b s t r a c t Recent findings regarding different characteristics according to the age of tinnitus

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

    PubMed

    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. PMID:19793311

  3. Do Substance Use Risk Personality Dimensions Predict the Onset of Substance Use in Early Adolescence? A Variable- and Person-Centered Approach

    ERIC Educational Resources Information Center

    Malmberg, Monique; Kleinjan, Marloes; Vermulst, Ad A.; Overbeek, Geertjan; Monshouwer, Karin; Lammers, Jeroen; Engels, Rutger C. M. E.

    2012-01-01

    Various studies found personality to be related to substance use, but little attention is paid to the role of personality risk dimensions with regard to an early onset of alcohol, tobacco, and marijuana use. Therefore, the current study used a variable-centered approach to examine whether anxiety sensitivity, hopelessness, sensation seeking, and…

  4. Mutations in presenilin 1, presenilin 2 and amyloid precursor protein genes in patients with early-onset Alzheimer's disease in Poland

    Microsoft Academic Search

    Cezary ?ekanowski; Maria Styczy?ska; Beata Pep?o?ska; Tomasz Gabryelewicz; Dorota Religa; Jan Ilkowski; Beata Kijanowska-Ha?adyna; S?awomira Kotapka-Minc; Sanne Mikkelsen; Anna Pfeffer; Anna Barczak; El?bieta ?uczywek; Bogus?aw Wasiak; Ma?gorzata Chodakowska-?ebrowska; Katarzyna Gustaw; Jaros?aw ??czkowski; Tomasz Sobów; Jacek Ku?nicki; Maria Barcikowska

    2003-01-01

    Mutations in three causative genes have been identified in patients with an autosomal-dominant form of early-onset Alzheimer's disease (EOAD). To determine the spectrum of mutations in a group consisting of 40 Polish patients with clinically diagnosed familial EOAD and 1 patient with mild cognitive impairment (MCI) and family history of AD, we performed a screening for mutations in the presenilin

  5. An Ultrasonographic Periodontal Probe

    NASA Astrophysics Data System (ADS)

    Bertoncini, C. A.; Hinders, M. K.

    2010-02-01

    Periodontal disease, commonly known as gum disease, affects millions of people. The current method of detecting periodontal pocket depth is painful, invasive, and inaccurate. As an alternative to manual probing, an ultrasonographic periodontal probe is being developed to use ultrasound echo waveforms to measure periodontal pocket depth, which is the main measure of periodontal disease. Wavelet transforms and pattern classification techniques are implemented in artificial intelligence routines that can automatically detect pocket depth. The main pattern classification technique used here, called a binary classification algorithm, compares test objects with only two possible pocket depth measurements at a time and relies on dimensionality reduction for the final determination. This method correctly identifies up to 90% of the ultrasonographic probe measurements within the manual probe's tolerance.

  6. Periodontitis and pregnancy.

    PubMed

    Tucker, Richard

    2006-01-01

    There is an increasing amount of evidence suggesting a systemic link between periodontal disease in the pregnant mother and pre-term low birth weight (PLBW). Severe periodontitis affects at least 10% of the general population. The aetiology of periodontitis is essentially a bacterially induced inflammatory reaction within the attachment surrounding the teeth. Maternal infection has been linked with pre-term delivery. Normal pregnancy itself is associated with inflammatory changes very similar to those found in sepsis. Because the infected periodontal tissues can act as a reservoir for both bacterial products and inflammatory cytokines, it may be possible that periodontal infection and the resultant inflammation could be linked with PLBW. Current understanding suggests that prostaglandins and proinflammatory cytokines play a pivotal role in the initiation process because of the close relationship of inflammation and infection. High levels of maternally or fetally derived cytokines such as tumour necrosis factor alpha (TNFalpha) may enhance amniochorionic and decidual interleukin six (IL-6) expression. Prostaglandin E2 (PGE2) has also been associated with periodontitis and PLBW. Periodontitis is a possible risk factor for PLBW with an odds ratio of 2.30. For the majority of individuals affected with periodontitis, the condition is symptom-free until the disease is more advanced. Therefore there is the need for medical carers of pregnant patients to increase the awareness among pregnant women themselves. Although there is plenty of evidence associating periodontitis with PLBW, interventional studies for the treatment of periodontitis measuring the impact on PLBW are few in number. Therefore more good quality clinical trials are required to address this issue. PMID:16478012

  7. Efficacy and safety of a routine early invasive strategy in relation to time from symptom onset to fibrinolysis (a subgroup analysis of TRANSFER-AMI).

    PubMed

    Russo, Juan J; Goodman, Shaun G; Cantor, Warren J; Tan, Mary K; Borgundvaag, Bjug; Fitchett, David; Džavík, Vladimír; Yan, Raymond T; Graham, John J; Mehta, Shamir R; Yan, Andrew T

    2015-04-15

    The aim of this study was to assess the efficacy and safety of an early invasive strategy post-fibrinolysis in relation to time from symptom onset to fibrinolysis in patients with ST-elevation myocardial infarction (STEMI). The Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) randomized 1,059 patients receiving fibrinolysis for STEMI to an early invasive strategy versus standard therapy. The primary end point was the composite of death, reinfarction, recurrent ischemia, new or worsening heart failure, or cardiogenic shock at 30 days. In this post hoc subgroup analysis, we examined the effect of an early invasive strategy on efficacy and safety outcomes after stratification by time from symptom onset to fibrinolysis (<2 or ?2 hours). Of 1,059 patients in TRANSFER-AMI, 557 (53%) received fibrinolysis <2 hours and 502 (47%) ?2 hours after symptom onset. Compared to patients who received fibrinolysis within 2 hours of symptoms, patients who received fibrinolysis ?2 hours after symptom onset had higher Global Registry of Acute Coronary Events risk scores (median 127 vs 122, p = 0.004). The effect of an early invasive strategy did not differ between symptom-to-fibrinolysis time strata for the primary efficacy end point (p-heterogeneity = 0.67), 30-day mortality, the composite of death or reinfarction at 30 days, 6 months, or 1 year, or bleeding (all p-heterogeneity >0.40). In conclusion, the efficacy and safety of an early invasive strategy in patients undergoing fibrinolysis for STEMI do not vary in relation to time (<2 or ?2 hours) from symptom onset to fibrinolysis. PMID:25711435

  8. Clinical evaluation of salivary periodontal pathogen levels by real-time polymerase chain reaction in patients before dental implant treatment

    PubMed Central

    Ito, Taichi; Yasuda, Masaaki; Kaneko, Hajime; Sasaki, Hodaka; Kato, Tetsuo; Yajima, Yasutomo

    2014-01-01

    Objective Periodontal pathogens in dental plaque are the main causative agents of periodontitis and peri-implantitis. Detection of the presence of such periodontal pathogens early would serve as a useful tool in the diagnosis and treatment of this disease. Therefore, the purpose of this study was to investigate whether the periodontal pathogen levels in saliva were correlated with the periodontal status of patients receiving implant treatment. Materials and Methods A total of 291 patients visiting Tokyo Dental College Chiba Hospital were divided into four groups: a no-periodontitis (np) group, a mild-periodontitis (mip) group, a moderate-periodontitis (mop) group, and a severe-periodontitis (sp) group. The levels of the following five periodontal pathogens in saliva were evaluated using real-time polymerase chain reaction: Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia, Treponema denticola, and Prevotella intermedia. Results The levels of P. gingivalis and T. forsythia were significantly higher in mop group than in np group (P <  0.05). The levels of all periodontal pathogens tested except A. actinomycetemcomitans were significantly higher in sp group than in np group (P <  0.05). Conclusion The detection levels of the periodontal pathogens targeted in saliva samples were correlated with the periodontal status. This suggests that using saliva to screen for periodontopathic bacteria offers an easier-to-use clinical tool than the paper point method in the diagnosis and treatment of periodontitis and peri-implantitis. PMID:23745964

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

    SciTech Connect

    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 (/sup 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.

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

    PubMed

    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. PMID:25259947

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

    PubMed Central

    Gong, Bo; Wei, Bo; Huang, Lulin; Hao, Jilong; Li, Xiulan; Yang, Yin; Zhou, Yu; Hao, Fang; Cui, Zhihua; Zhang, Dingding; Wang, Le

    2015-01-01

    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

  12. Early and Late De Novo Tumors after Liver Transplantation in Adults: The Late Onset of Bladder Tumors in Men

    PubMed Central

    Maggi, Umberto; Consonni, Dario; Manini, Matteo Angelo; Gatti, Stefano; Cuccaro, Francesco; Donato, Francesca; Conte, Grazia; Bertazzi, Pier Alberto; Rossi, Giorgio

    2013-01-01

    Background De novo tumors (DNT) after liver transplantation (LT) represent a growing concern. Patients and Methods We analyzed the incidence of DNT, type, time of onset, risk factors and mortality (as of 2010) in 494 adult patients transplanted in the last 26 years (1983–2009). Results DNT occurred in 41 (8.3%) of the patients. The Standardized Incidence Ratio (SIR) compared with the Italian population was 1.8. There was a higher incidence in males (SIR 2.0), an expected extremely high rate of Kaposi’s sarcoma (SIR 127.95) and unexpected higher rates of tumors of the bladder in males (SIR 3.3). The incidence of DNT was higher within the first two years of LT (SIR 2.7) for Kaposi’s sarcoma (SIR 393.3) and after 10 years (SIR 1.7) for bladder tumors (SIR 10.6). Multivariate analysis identified alcoholic cirrhosis (HR?=?3.0, 95% CI?=?1.2–7.8) and sclerosing cholangitis (HR?=?3.5, 95% CI?=?1.1–11.3) in the recipient as main risk factors for the occurrence of DNT. Conclusions Surveillance protocols for DNT must be specifically oriented to patients transplanted for alcoholic cirrhosis and sclerosing cholangitis. They should focus on early detection of Kaposi’s sarcomas, and more remarkably, on late development bladder tumors in men after LT. PMID:23785414

  13. A co-expression network analysis reveals lncRNA abnormalities in peripheral blood in early-onset schizophrenia.

    PubMed

    Ren, Yan; Cui, Yuehua; Li, Xinrong; Wang, Binhong; Na, Long; Shi, Junyan; Wang, Liang; Qiu, Lixia; Zhang, Kerang; Liu, Guifen; Xu, Yong

    2015-12-01

    Long non-coding RNAs (lncRNAs) are emerging as important regulators of gene expression and disease processes especially in neuropsychiatric disorders. To explore the potential regulatory roles of lncRNAs in schizophrenia, we performed an integrated co-expression network analysis on lncRNA and mRNA microarray profiles generated from the peripheral blood samples in 19 drug-naïve first-episode early-onset schizophrenia (EOS) patients and 18 demographically matched typically developing controls (TDCs). Using weighted gene co-expression network analysis (WGCNA), we showed that the lncRNAs were organized into co-expressed modules, and two lncRNA modules were associated with EOS. The mRNA networks were constructed and three disease-associated modules were identified. Gene Ontology (GO) analysis indicated that the mRNAs were highly enriched for mitochondrion and related biological processes. Moreover, our results revealed a significant correlation between lncRNAs and mRNAs using the canonical correlation analysis (CCA). Our results suggest that the convergent lncRNA alteration may be involved in the etiologies of EOS, and mitochondrial dysfunction participates in the pathological process of the disease. Our findings may shed light on the pathogenesis of schizophrenia and facilitate future diagnosis and therapeutic strategies. PMID:25967042

  14. Novel ANKH Amino Terminus Mutation (Pro5Ser) Associated With Early-Onset Calcium Pyrophosphate Disease With Associated Phosphaturia

    PubMed Central

    Gruber, Barry L.; Couto, Ana Rita; Armas, Jácome Bruges; Brown, Matthew A.; Finzel, Kathleen; Terkeltaub, Robert A.

    2015-01-01

    This report describes a 32-year-old woman presenting since childhood with progressive calcium pyrophosphate disease (CPPD), characterized by severe arthropathy and chondrocalcinosis involving multiple peripheral joints and intervertebral disks. Because ANKH mutations have been previously described in familial CPPD, the proband’s DNA was assessed at this locus by direct sequencing of promoter and coding regions and revealed 3 sequence variants in ANKH. Sequences of exon 1 revealed a novel isolated nonsynonymous mutation (c.13 C>T), altering amino acid in codon 5 from proline to serine (CCG>TCG). Sequencing of parental DNA revealed an identical mutation in the proband’s father but not the mother. Subsequent clinical evaluation demonstrated extensive chondrocalcinosis and degenerative arthropathy in the proband’s father. In summary, we report a novel mutation, not previously described, in ANKH exon 1, wherein serine replaces proline, in a case of early-onset severe CPPD associated with metabolic abnormalities, with similar findings in the proband’s father. PMID:22647861

  15. Adolescent-onset alcohol abuse exacerbates the influence of childhood conduct disorder on late adolescent and early adult antisocial behaviour

    PubMed Central

    Howard, Richard; Finn, Peter; Jose, Paul; Gallagher, Jennifer

    2012-01-01

    This study tested the hypothesis that adolescent-onset alcohol abuse (AOAA) would both mediate and moderate the effect of childhood conduct disorder on antisocial behaviour in late adolescence and early adulthood. A sample comprising 504 young men and women strategically recruited from the community were grouped using the criteria of the Diagnostic and Statistical Manual (DSM-IV, American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th ed.). Washington, DC: APA), as follows: neither childhood conduct disorder (CCD) nor alcohol abuse/dependence; CCD but no alcohol abuse or dependence; alcohol abuse/dependence but no CCD; both CCD and alcohol abuse/dependence. The outcome measure was the sum of positive responses to 55 interview items capturing a variety of antisocial behaviours engaged in since age 15. Severity of lifetime alcohol-related and CCD problems served as predictor variables in regression analysis. Antisocial behaviour problems were greatest in individuals with a history of co-occurring conduct disorder (CD) and alcohol abuse/dependence. While CCD was strongly predictive of adult antisocial behaviour, this effect was both mediated and moderated (exacerbated) by AOAA. PMID:23459369

  16. Germline mutations in CDH1 are infrequent in women with early-onset or familial lobular breast cancers

    PubMed Central

    Schrader, K A; Masciari, S; Boyd, N; Salamanca, C; Senz, J; Saunders, D N; Yorida, E; Maines-Bandiera, S; Kaurah, P; Tung, N; Robson, M E; Ryan, P D; Olopade, O I; Domchek, S M; Ford, J; Isaacs, C; Brown, P; Balmana, J; Razzak, A R; Miron, P; Coffey, K; Terry, M B; John, E M; Andrulis, I L; Knight, J A; O'Malley, F P; Daly, M; Bender, P; Moore, R; Southey, M C; Hopper, J L; Garber, J E

    2010-01-01

    Background Germline mutations in CDH1 are associated with hereditary diffuse gastric cancer; lobular breast cancer also occurs excessively in families with such condition. Method To determine if CDH1 is a susceptibility gene for lobular breast cancer in women without a family history of diffuse gastric cancer, germline DNA was analysed for the presence of CDH1 mutations in 318 women with lobular breast cancer who were diagnosed before the age of 45?years or had a family history of breast cancer and were not known, or known not, to be carriers of germline mutations in BRCA1 or BRCA2. Cases were ascertained through breast cancer registries and high-risk cancer genetic clinics (Breast Cancer Family Registry, the kConFab and a consortium of breast cancer genetics clinics in the United States and Spain). Additionally, Multiplex Ligation-dependent Probe Amplification was performed for 134 cases to detect large deletions. Results No truncating mutations and no large deletions were detected. Six non-synonymous variants were found in seven families. Four (4/318 or 1.3%) are considered to be potentially pathogenic through in vitro and in silico analysis. Conclusion Potentially pathogenic germline CDH1 mutations in women with early-onset or familial lobular breast cancer are at most infrequent. PMID:20921021

  17. Recurrent gain of function mutation in calcium channel CACNA1H causes early-onset hypertension with primary aldosteronism.

    PubMed

    Scholl, Ute I; Stölting, Gabriel; Nelson-Williams, Carol; Vichot, Alfred A; Choi, Murim; Loring, Erin; Prasad, Manju L; Goh, Gerald; Carling, Tobias; Juhlin, C Christofer; Quack, Ivo; Rump, Lars C; Thiel, Anne; Lande, Marc; Frazier, Britney G; Rasoulpour, Majid; Bowlin, David L; Sethna, Christine B; Trachtman, Howard; Fahlke, Christoph; Lifton, Richard P

    2015-01-01

    Many Mendelian traits are likely unrecognized owing to absence of traditional segregation patterns in families due to causation by de novo mutations, incomplete penetrance, and/or variable expressivity. Genome-level sequencing can overcome these complications. Extreme childhood phenotypes are promising candidates for new Mendelian traits. One example is early onset hypertension, a rare form of a global cause of morbidity and mortality. We performed exome sequencing of 40 unrelated subjects with hypertension due to primary aldosteronism by age 10. Five subjects (12.5%) shared the identical, previously unidentified, heterozygous CACNA1H(M1549V) mutation. Two mutations were demonstrated to be de novo events, and all mutations occurred independently. CACNA1H encodes a voltage-gated calcium channel (CaV3.2) expressed in adrenal glomerulosa. CACNA1H(M1549V) showed drastically impaired channel inactivation and activation at more hyperpolarized potentials, producing increased intracellular Ca(2+), the signal for aldosterone production. This mutation explains disease pathogenesis and provides new insight into mechanisms mediating aldosterone production and hypertension. PMID:25907736

  18. Early onset of virus infection and up-regulation of cytokines in mice treated with cadmium and manganese.

    PubMed

    Seth, Pankaj; Husain, Mirza M; Gupta, Pratibha; Schoneboom, A; Grieder, Bruce Franziska B; Mani, Haresh; Maheshwari, Radha K

    2003-06-01

    A substantial database indicates that a large number of environmental pollutants, chemicals and therapeutic agents to which organisms are exposed cause immunotoxicity. The suppression of immune functions may cause increased susceptibility of the host to a variety of microbial pathogens potentially resulting in a life-threatening state. Evaluation of the immunotoxic potential of chemical xenobiotics is of great concern and, therefore, we have investigated the impact of exposure of inorganic metals, specifically cadmium (Cd) and manganese (Mn) on Encephalomyocarditis virus (EMCV), Semliki Forest virus (SFV), and Venezuelan Equine Encephalitis virus (VEEV) infection. Pretreatment with a single, oral dose of Cd or Mn increased the susceptibility of mice to a sub-lethal infection of these viruses as observed by increased severity of symptoms and mortality compared to untreated controls. An early onset of virus infection was found in brains of Cd and Mn treated animals. Histopathological observations of the brain indicate evidence of inflammation and greater tissue pathology in Cd-or Mn-exposed mice compared to control animals. Meningitis and vascular congestion was seen in virus infected mice in all the metal treated groups, and further, the perivascular inflammation appeared earlier in treated mice compared to control. Encephalitis was maximum in Cd pretreated mice. Widespread environmental contamination of metals and the potential for their exposure and subsequent infection of humans or animals is indicative that further studies of these and all other metals are important to understand the effect of environmental pollution on human health. PMID:12572694

  19. HMGB1 Localization during Experimental Periodontitis

    PubMed Central

    Chaves de Souza, João Antonio; da Silva Mariano Pereira, Elyne; de Aquino, Sabrina Garcia; Giannobile, William V.; Cirelli, Joni Augusto

    2014-01-01

    Aim. This study sought to investigate the in vitro expression profile of high mobility group box 1 (HMGB1) in murine periodontal ligament fibroblasts (mPDL) stimulated with LPS or IL-1? and in vivo during ligature- or LPS-induced periodontitis in rats. Material and Methods. For the in vivo study, 36 rats were divided into experimental and control groups, and biopsies were harvested at 7–30?d following disease induction. Bone loss and inflammation were evaluated. HMGB1 expression was assessed by immunohistochemistry, qPCR, and Western blot. Results. Significant increases in mPDL HMGB1 mRNA occurred at 4, 8, and 12?h with protein expression elevated by 24?h. HMGB1 mRNA expression in gingival tissues was significantly increased at 15?d in the LPS-PD model and at 7 and 15?d in the ligature model. Immunohistochemical staining revealed a significant increase in the number of HMGB1-positive cells during the experimental periods. Conclusion. The results show that PDL cells produce HMGB1, which is increased and secreted extracellularly after inflammatory stimuli. In conclusion, this study demonstrates that HMGB1 may be associated with the onset and progression of periodontitis, suggesting that further studies should investigate the potential role of HMGB1 on periodontal tissue destruction. PMID:24692854

  20. Risk factors for naturally-occurring early-onset hepatocellular carcinoma in patients with HBV-associated liver cirrhosis in China

    PubMed Central

    Li, Yuanyuan; Zhang, Zheng; Shi, Jianfei; Jin, Lei; Wang, Lifeng; Xu, Dongping; Wang, Fu-Sheng

    2015-01-01

    Aims: Early onset of hepatocellular carcinoma (HCC) (males and females under the age of 40 or 50 years old, respectively) has a significant prevalence and poor prognosis; however, few studies have reported the risk factors and development of HCC in such cases. Methods: In this study, we retrospectively analyzed clinical, laboratory and demographic data from 588 treatment-naïve HCC patients with hepatitis B virus (HBV)-associated liver cirrhosis (LC) and 708 age-matched HBV-associated LC patients as control in Beijing 302 Hospital. Results: 15.1% (89/588) of the HCC patients and 36.7% (181/708) of the LC patients were classified as early onset. Compared with age-matched LC controls, male gender (odds ratio (OR) = 2.09, P < 0.05), family history of HBV infection (OR = 2.45, P < 0.05) and alpha-fetoprotein (AFP) > 200 ng/ml (OR = 30.8, P < 0.05) were independent risk factors for early-onset HCC. Comparing late-onset LC controls, male gender (OR = 1.92, P < 0.05), age (OR = 1.04, P < 0.05), family history of HCC (OR = 2.06, P < 0.05), history of smoking (OR = 1.68, P < 0.05) and AFP > 200 ng/ml (OR = 12.0, P < 0.05) were associated with the development of naturally occurring HCC. Overall, male gender and AFP > 200 ng/ml is associated with HCC development across all ages, whereas a family history of HBV infection may identify younger HBV-associated LC patients at risk for HCC. Conclusion: Our data suggest that a family history of HBV infection is a unique risk factor for naturally-occurring early-onset HCC patients with HBV-associated LC, who should be considered for intensive screening programs. PMID:25785114

  1. Genetic score based on high-risk genetic polymorphisms and early onset of ischemic heart disease in an Italian cohort of ischemic patients.

    PubMed

    Vecoli, Cecilia; Adlerstein, Daniel; Shehi, Erlet; Bigazzi, Federico; Sampietro, Tiziana; Foffa, Ilenia; Carpeggiani, Clara; L'abbate, Antonio; Andreassi, Maria Grazia

    2014-05-01

    Several single-nucleotide polymorphisms (SNPs) have been recognized as associated with ischemic heart disease (IHD) although the optimal set of risk genotypes has not be identified. This study aimed to examine whether identified high-risk SNPs are associated with early onset of IHD. In the GENOCOR study, 44 high-risk SNPs were genotyped in 114 patients with early onset of IHD (46.2 ± 5.1 years) and 384 patients with late onset of IHD (60.7 ± 5.9 years). The associations between individual SNPs and early onset IHD were assessed. A multilocus genetic risk score (GRS) for each associated risk genetic markers was constructed by summing the number of risk alleles. The SNPs significantly associated with IHD were: -482C>T of Apolipoprotein C III gene (ApoC3, p=0.02); 1171 5A>6A of Matrix metalloproteinase 3 stromelisine I gene (p=0.01); G98T of Selectin E gene (p=0.05); C/G of 9p21.3 locus (p=0.01). Likelihood ratio test showed a strong interaction for increasing risk of early IHD between the presence of ApoC3 and 9p21.3 locus with hypertriglyceridemia (p=0.0008, 0.0011) as well as between 9p21.3 locus and smoking (p=0.0010) after correction for multiple testing. The OR for premature IHD for GRS unit was 1.3 (95% CI 1.1-1.6, p=0.001). Patients in the top tertile of GRS were estimated to have a 3.2-fold (95% CI 1.5-6.8; p=0.001) increased risk of early IHD compared with those in the bottom tertile. The results show that currently identified high-risk SNPs confer an additive biomarker for cardiovascular events. GRS may provide important incremental information on the genetic component of IHD. PMID:24656450

  2. Periodontitis diagnostics using resonance Raman spectroscopy on saliva

    NASA Astrophysics Data System (ADS)

    Gonchukov, S.; Sukhinina, A.; Bakhmutov, D.; Biryukova, T.; Tsvetkov, M.; Bagratashvily, V.

    2013-07-01

    In view of its wealth of molecular information, Raman spectroscopy has been the subject of active biomedical research. The aim of this work is Raman spectroscopy (RS) application for the determination of molecular biomarkers in saliva with the objective of early periodontitis detection. As was shown in our previous study, carotenoids contained in saliva can be molecular fingerprint information for the periodontitis level. It is shown here that the carotenoid RS lines at wavenumbers of 1156 and 1524 cm?1 can be easily detected and serve as reliable biomarkers of periodontitis using resonance Raman spectroscopy of dry saliva.

  3. Diagnosis of Periodontal Diseases

    Microsoft Academic Search

    R. R. Ranney

    1991-01-01

    This paper reviews current (Fall, 1990) information related to the diagnosis of periodontal diseases. As background, principles of diagnostic decision-making and conceptual shifts during the 1970's and 1980's are reviewed in brief. \\

  4. Periodontal Treatments and Procedures

    MedlinePLUS

    ... Procedures Non-Surgical Periodontal Treatments Gum Graft Surgery Laser Treatment for Gum Disease Regenerative Procedures Dental Crown Lengthening ... dental implants. Non-Surgical Treatments Gum Graft Surgery Laser Treatment Regenerative Procedures Dental Crown Lengthening Dental Implants Pocket ...

  5. Differential activation of placental unfolded protein response pathways implies heterogeneity in causation of early- and late-onset pre-eclampsia.

    PubMed

    Yung, Hong Wa; Atkinson, Daniel; Campion-Smith, Tim; Olovsson, Matts; Charnock-Jones, D Stephen; Burton, Graham J

    2014-10-01

    Based on gestational age at diagnosis and/or delivery, pre-eclampsia (PE) is commonly divided into early-onset (<34 weeks) and late-onset (?34 weeks) forms. Recently, the distinction between 'placental' and 'maternal' causation has been proposed, with 'placental' cases being more frequently associated with early-onset and intrauterine growth restriction. To test whether molecular placental pathology varies according to clinical presentation, we investigated stress-signalling pathways, including unfolded protein response (UPR) pathways, MAPK stress pathways, heat-shock proteins and AMPK? in placentae delivered by caesarean section for clinical indications at different gestational ages. Controls included second-trimester, pre-term and normal-term placentae. BeWo cells were used to investigate how these pathways react to different severities of hypoxia-reoxygenation (H/R) and pro-inflammatory cytokines. Activation of placental UPR and stress-response pathways, including P-IRE1?, ATF6, XBP-1, GRP78 and GRP94, P-p38/p38 and HSP70, was higher in early-onset PE than in both late-onset PE and normotensive controls (NTCs), with a clear inflection around 34 weeks. Placentae from ? 34 weeks PE and NTC were indistinguishable. Levels of UPR signalling were similar between second-trimester and term controls, but were significantly higher in pre-term 'controls' delivered vaginally for chorioamnionitis and other conditions. Severe H/R (1/20% O2 ) induced equivalent activation of UPR pathways, including P-eIF2?, ATF6, P-IRE1?, GRP78 and GRP94, in BeWo cells. By contrast, the pro-inflammatory cytokines TNF? and IL-1? induced only mild activation of P-eIF2? and GRP78. AKT, a central regulator of cell proliferation, was reduced in the < 34 weeks PE placentae and severe H/R-treated cells, but not in other conditions. These findings provide the first molecular evidence that placental stress may contribute to the pathophysiology of early-onset pre-eclampsia, whereas that is unlikely to be the case in the late-onset form of the syndrome. PMID:24931423

  6. Differential activation of placental unfolded protein response pathways implies heterogeneity in causation of early- and late-onset pre-eclampsia

    PubMed Central

    Yung, Hong Wa; Atkinson, Daniel; Campion-Smith, Tim; Olovsson, Matts; Charnock-Jones, D Stephen; Burton, Graham J

    2014-01-01

    Based on gestational age at diagnosis and/or delivery, pre-eclampsia (PE) is commonly divided into early-onset (<34 weeks) and late-onset (?34 weeks) forms. Recently, the distinction between ‘placental’ and ‘maternal’ causation has been proposed, with ‘placental’ cases being more frequently associated with early-onset and intrauterine growth restriction. To test whether molecular placental pathology varies according to clinical presentation, we investigated stress-signalling pathways, including unfolded protein response (UPR) pathways, MAPK stress pathways, heat-shock proteins and AMPK? in placentae delivered by caesarean section for clinical indications at different gestational ages. Controls included second-trimester, pre-term and normal-term placentae. BeWo cells were used to investigate how these pathways react to different severities of hypoxia–reoxygenation (H/R) and pro-inflammatory cytokines. Activation of placental UPR and stress-response pathways, including P-IRE1?, ATF6, XBP-1, GRP78 and GRP94, P-p38/p38 and HSP70, was higher in early-onset PE than in both late-onset PE and normotensive controls (NTCs), with a clear inflection around 34 weeks. Placentae from ? 34 weeks PE and NTC were indistinguishable. Levels of UPR signalling were similar between second-trimester and term controls, but were significantly higher in pre-term ‘controls’ delivered vaginally for chorioamnionitis and other conditions. Severe H/R (1/20% O2) induced equivalent activation of UPR pathways, including P-eIF2?, ATF6, P-IRE1?, GRP78 and GRP94, in BeWo cells. By contrast, the pro-inflammatory cytokines TNF? and IL-1? induced only mild activation of P-eIF2? and GRP78. AKT, a central regulator of cell proliferation, was reduced in the < 34 weeks PE placentae and severe H/R-treated cells, but not in other conditions. These findings provide the first molecular evidence that placental stress may contribute to the pathophysiology of early-onset pre-eclampsia, whereas that is unlikely to be the case in the late-onset form of the syndrome. © 2014 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. PMID:24931423

  7. Recessive Mutations in the ?3 (VI) Collagen Gene COL6A3 Cause Early-Onset Isolated Dystonia.

    PubMed

    Zech, Michael; Lam, Daniel D; Francescatto, Ludmila; Schormair, Barbara; Salminen, Aaro V; Jochim, Angela; Wieland, Thomas; Lichtner, Peter; Peters, Annette; Gieger, Christian; Lochmüller, Hanns; Strom, Tim M; Haslinger, Bernhard; Katsanis, Nicholas; Winkelmann, Juliane

    2015-06-01

    Isolated dystonia is a disorder characterized by involuntary twisting postures arising from sustained muscle contractions. Although autosomal-dominant mutations in TOR1A, THAP1, and GNAL have been found in some cases, the molecular mechanisms underlying isolated dystonia are largely unknown. In addition, although emphasis has been placed on dominant isolated dystonia, the disorder is also transmitted as a recessive trait, for which no mutations have been defined. Using whole-exome sequencing in a recessive isolated dystonia-affected kindred, we identified disease-segregating compound heterozygous mutations in COL6A3, a collagen VI gene associated previously with muscular dystrophy. Genetic screening of a further 367 isolated dystonia subjects revealed two additional recessive pedigrees harboring compound heterozygous mutations in COL6A3. Strikingly, all affected individuals had at least one pathogenic allele in exon 41, including an exon-skipping mutation that induced an in-frame deletion. We tested the hypothesis that disruption of this exon is pathognomonic for isolated dystonia by inducing a series of in-frame deletions in zebrafish embryos. Consistent with our human genetics data, suppression of the exon 41 ortholog caused deficits in axonal outgrowth, whereas suppression of other exons phenocopied collagen deposition mutants. All recessive mutation carriers demonstrated early-onset segmental isolated dystonia without muscular disease. Finally, we show that Col6a3 is expressed in neurons, with relevant mRNA levels detectable throughout the adult mouse brain. Taken together, our data indicate that loss-of-function mutations affecting a specific region of COL6A3 cause recessive isolated dystonia with underlying neurodevelopmental deficits and highlight the brain extracellular matrix as a contributor to dystonia pathogenesis. PMID:26004199

  8. Mimicry of the pathogenic mycobacterium vacuole in vitro elicits the bacterial intracellular phenotype, including early-onset macrophage death.

    PubMed

    Early, Julie; Bermudez, Luiz E

    2011-06-01

    Mycobacterium avium complex (MAC) within macrophages undergoes a phenotype change that allows for more efficient entry into surrounding host cells. We hypothesized that, by developing an in vitro system resembling the intravacuolar environment, one could generate insights into the mycobacterial intracellular phenotype. MAC was incubated in "elemental mixtures" that reproduce metal concentrations and pH in the vacuoles at different time points and then used to infect fresh macrophages. Incubation of MAC with the mixture corresponding to the vacuole environment 24 h postinfection infected macrophages at a significantly higher rate than bacteria that were incubated in Middlebrook 7H9 broth. Uptake occurred by macropinocytosis, similar to the uptake of bacteria passed through macrophages. Genes reported to be upregulated in intracellular bacteria, such as Mav1365, Mav2409, Mav4487, and Mav0996, were upregulated in MAC incubated in the 24-h elemental mixture. Like MAC obtained from macrophages, the vacuoles of bacteria from the 24-h elemental mixture were more likely to contain lysosome-associated membrane protein 1 (LAMP-1). A stepwise reduction scheme of the 24-h elemental mixture indicated that incubation in physiologically relevant concentrations of potassium chloride, calcium chloride, and manganese chloride was sufficient to induce characteristics of the intracellular phenotype. It was demonstrated that bacteria harboring the intracellular phenotype induced early-onset macrophage death more efficiently than bacteria grown in broth. This new trace elemental mixture mimicking the condition of the vacuole at different time points has the potential to become an effective laboratory tool for the study of the MAC and Mycobacterium tuberculosis disease process, increasing the understanding of the interaction with macrophages. PMID:21444666

  9. Sporadic Early-Onset Colorectal Cancer Is a Specific Sub-Type of Cancer: A Morphological, Molecular and Genetics Study

    PubMed Central

    Kirzin, Sylvain; Marisa, Laetitia; Guimbaud, Rosine; De Reynies, Aurélien; Legrain, Michèle; Laurent-Puig, Pierre; Cordelier, Pierre; Pradère, Bernard; Bonnet, Delphine; Meggetto, Fabienne; Portier, Guillaume; Brousset, Pierre; Selves, Janick

    2014-01-01

    Sporadic early onset colorectal carcinoma (EOCRC) which has by definition no identified hereditary predisposition is a growing problem that remains poorly understood. Molecular analysis could improve identification of distinct sub-types of colorectal cancers (CRC) with therapeutic implications and thus can help establish that sporadic EOCRC is a distinct entity. From 954 patients resected for CRC at our institution, 98 patients were selected. Patients aged 45–60 years were excluded to help define “young” and “old” groups. Thirty-nine cases of sporadic EOCRC (patients?45 years with microsatellite stable tumors) were compared to both microsatellite stable tumors from older patients (36 cases, patients>60 years) and to groups of patients with microsatellite instability. Each group was tested for TP53, KRAS, BRAF, PIK3CA mutations and the presence of a methylator phenotype. Gene expression profiles were also used for pathway analysis. Compared to microsatellite stable CRC from old patients, sporadic EOCRC were characterized by distal location, frequent synchronous metastases and infrequent synchronous adenomas but did not have specific morphological characteristics. A familial history of CRC was more common in sporadic EOCRC patients despite a lack of identified hereditary conditions (p?=?0.013). Genetic studies also showed the absence of BRAF mutations (p?=?0.022) and the methylator phenotype (p?=?0.005) in sporadic EOCRC compared to older patients. Gene expression analysis implicated key pathways such as Wnt/beta catenin, MAP Kinase, growth factor signaling (EGFR, HGF, PDGF) and the TNFR1 pathway in sporadic EOCRC. Wnt/beta catenin signaling activation was confirmed by aberrant nuclear beta catenin immunostaining (p?=?0.01). This study strongly suggests that sporadic EOCRC is a distinct clinico-molecular entity presenting as a distal and aggressive disease associated with chromosome instability. Furthermore, several signaling pathways including the TNFR1 pathway have been identified as potential biomarkers for both the diagnosis and treatment of this disease. PMID:25083765

  10. Biomaterials for periodontal regeneration

    PubMed Central

    Shue, Li; Yufeng, Zhang; Mony, Ullas

    2012-01-01

    Periodontal disease is characterized by the destruction of periodontal tissues. Various methods of regenerative periodontal therapy, including the use of barrier membranes, bone replacement grafts, growth factors and the combination of these procedures have been investigated. The development of biomaterials for tissue engineering has considerably improved the available treatment options above. They fall into two broad classes: ceramics and polymers. The available ceramic-based materials include calcium phosphate (eg, tricalcium phosphate and hydroxyapatite), calcium sulfate and bioactive glass. The bioactive glass bonds to the bone with the formation of a layer of carbonated hydroxyapatite in situ. The natural polymers include modified polysaccharides (eg, chitosan,) and polypeptides (collagen and gelatin). Synthetic polymers [eg, poly(glycolic acid), poly(L-lactic acid)] provide a platform for exhibiting the biomechanical properties of scaffolds in tissue engineering. The materials usually work as osteogenic, osteoconductive and osteoinductive scaffolds. Polymers are more widely used as a barrier material in guided tissue regeneration (GTR). They are shown to exclude epithelial downgrowth and allow periodontal ligament and alveolar bone cells to repopulate the defect. An attempt to overcome the problems related to a collapse of the barrier membrane in GTR or epithelial downgrowth is the use of a combination of barrier membranes and grafting materials. This article reviews various biomaterials including scaffolds and membranes used for periodontal treatment and their impacts on the experimental or clinical management of periodontal defect. PMID:23507891

  11. Evolution of volcanically-induced palaeoenvironmental changes leading to the onset of OAE1a (early Aptian, Cretaceous)

    NASA Astrophysics Data System (ADS)

    Keller, Christina E.; Hochuli, Peter A.; Giorgioni, Martino; Garcia, Therese I.; Bernasconi, Stefano M.; Weissert, Helmut

    2010-05-01

    During the Cretaceous, several major volcanic events occurred that initiated climate warming, altered marine circulation and increased marine productivity, which in turn often resulted in the widespread black shale deposits of the Oceanic Anoxic Events (OAE). In the sediments underlying the early Aptian OAE1a black shales, a prominent negative carbon isotope excursion is recorded. Its origin had long been controversial (e.g. Arthur, 2000; Jahren et al., 2001) before recent studies attributed it to the Ontong Java volcanism (Méhay et al., 2009; Tejada et al., 2009). Therefore the negative C-isotope excursion covers the interval between the time, when volcanic activity became important enough to be recorded in the C-isotope composition of the oceans to the onset of widespread anoxic conditions (OAE1a). We chose this interval at the locality of Pusiano (N-Italy) to study the effect of a volcanically-induced increase in pCO2 on the marine palaeoenvironment and to observe the evolving palaeoenvironmental conditions that finally led to OAE1a. The Pusiano section (Maiolica Formation) was deposited at the southern continental margin of the alpine Tethys Ocean and has been bio- and magnetostratigraphically dated by Channell et al. (1995). We selected 18 samples from 12 black shale horizons for palynofacies analyses. Palynofacies assemblages consist of several types of particulate organic matter, providing information on the origin of the organic matter (terrestrial/marine) and conditions during deposition (oxic/anoxic). We then linked the palynofacies results to high-resolution inorganic and organic C-isotope values and total organic carbon content measurements. The pelagic Pusiano section consists of repeated limestone-black shale couplets, which are interpreted to be the result of changes in oxygenation of bottom waters. Towards the end of the negative C-isotope excursion we observe enhanced preservation of the fragile amorphous organic matter resulting in increased total organic carbon values in the black shale as well as in the limestone intervals. This shows how a rising pCO2 triggered changes in climate and oceanography and resulted in an increasing oxygen-deficiency of the bottom waters that persisted even during the 'limestone intervals' before oxygen-depletion finally became a global phenomenon. References: Arthur, M.A., 2000, Volcanic contributions to the carbon and sulfur geochemical cycles and global change, in Sigurdsson, H., Houghton, B., McNutt, S.R., Rymer, H., and Stix, J., eds., Encyclopedia of Volcanoes, Academic Press, p. 1045-1056. Channell, J.E.T., Cecca, F., and Erba, E., 1995, Correlations of Hauterivian and Barremian (Early Cretaceous) stage boundaries to polarity chrons: Earth and Planetary Science Letters, v. 134, p. 125-140. Jahren, A.H., Arens, N.C., Sarmiento, G., Guerrero, J., and Amundson, R., 2001, Terrestrial record of methane hydrate dissociation in the Early Cretaceous: Geology, v. 29, p. 159-162. Méhay, S., Keller, C.E., Bernasconi, S.M., Weissert, H., Erba, E., Bottini, C., and Hochuli, P.A., 2009, A volcanic CO2 pulse triggered the Cretaceous Oceanic Anoxic Event 1a and a biocalcification crisis: Geology, v. 37, p. 819-822. Tejada, M.L.G., Suzuki, K., Junichiro, K., Rodolfo, C., J., M.J., Naohiko, O., Tatsuhiko, S., and Yoshiyuki, T., 2009, Ontong Java Plateau eruption as a trigger for the early Aptian oceanic anoxic event: Geology, v. 37, p. 855-858.

  12. Early-onset acquired epileptic aphasia (Landau–Kleffner syndrome, LKS) and regressive autistic disorders with epileptic EEG abnormalities: The continuing debate

    Microsoft Academic Search

    Thierry Deonna; Eliane Roulet-Perez

    2010-01-01

    Early-onset acquired epileptic aphasia (Landau–Kleffner syndrome) may present as a developmental language disturbance and the affected child may also exhibit autistic features. Landau–Kleffner is now seen as the rare and severe end of a spectrum of cognitive-behavioural symptoms that can be seen in idiopathic (genetic) focal epilepsies of childhood, the benign end being the more frequent typical rolandic epilepsy. Several

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

    PubMed Central

    Lee, Ji Woo; Kim, Hyung Jin; Choe, Yun Mee; Kang, Hee Suk; Kim, Soon Ki; Jun, Yong Hoon

    2014-01-01

    Purpose Long-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. Methods This 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. Results Six 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. Conclusion Sterile 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. PMID:25346917

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

    PubMed

    Haroon, Munib

    2013-03-01

    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. PMID:23877887

  15. No increase in rates of early-onset neonatal sepsis by non-group B Streptococcus or ampicillin-resistant organisms

    Microsoft Academic Search

    Katherine T. Chen; Ruth E. Tuomala; Amy P. Cohen; Eric C. Eichenwald; Ellice Lieberman

    2001-01-01

    Objective: We assessed the impact of a risk-based approach to group B Streptococcus (GBS) prophylaxis on the rates of early-onset neonatal sepsis (EONS). Study Design: A retrospective cohort study of neonates born at a tertiary-care hospital from 1990 to 1996 was performed. Cases of EONS were identified among neonates born in a period without GBS prophylaxis (1990-1992) and compared with

  16. A Two-Base Deletion –439delGC in the Melanocortin-4 Receptor Promoter Associated with Early-Onset Obesity

    Microsoft Academic Search

    Kaisa Valli-Jaakola; Jorma J. Palvimo; Marita Lipsanen-Nyman; Veikko Salomaa; Leena Peltonen; Kimmo Kontula; Camilla Schalin-Jäntti

    2006-01-01

    Background\\/Aims: Mutations in melanocortin-4 receptor (MC4R) are the most common genetic cause of human obesity. Mutations in MC4R promoter could also underlie obesity, but have so far not been reported. Transcription factor nescient helix-loop-helix 2 (Nhlh2) is a novel obesity candidate gene. We searched for mutations in MC4R promoter and Nhlh2 gene in 152 children with severe early-onset obesity. Lean

  17. ARTICLES Family History of Breast and Ovarian Cancers and BRCA1 and BRCA2 Mutations in a Population-Based Series of Early-Onset Breast Cancer

    Microsoft Academic Search

    Niklas Loman; Oskar Johannsson; Ulf Kristoffersson; Håkan Olsson; Åke Borg

    Background: BRCA1 and BRCA2 are the two major suscep- tibility genes involved in hereditary breast cancer. This study was undertaken to provide reliable population-based estimates of genetic influence and to characterize the nature and prevalence of BRCA1 and BRCA2 germline mutations in early-onset breast cancer. Methods: In a series comprising all women diagnosed with breast cancer under the age of

  18. The DJ1L166P mutant protein associated with early onset Parkinson's disease is unstable and forms higher-order protein complexes

    Microsoft Academic Search

    Maria G. Macedo; Burcu Anar; Iraad F. Bronner; Milena Cannella; Ferdinando Squitieri; Vincenzo Bonifati; André Hoogeveen; Peter Heutink; Patrizia Rizzu

    2003-01-01

    Abstract Parkinson’s disease (PD) is a common,neurodegenerative disorder that involves the selective degeneration of midbrain dopaminergic,neurons. Recently DJ-1mutations have been linked to autosomal-recessive early-onset Parkinsoninsm in two European families. By using gel filtration assays under physiological conditions we demonstrate that DJ-1 protein forms a dimeric structure. Conversely, the DJ-1,mutant,protein in patient’s lymphoblasts is very low as compared to the wild

  19. Homozygosity for a novel missense mutation in the leptin receptor gene (P316T) in two Egyptian cousins with severe early onset obesity.

    PubMed

    Mazen, I; El-Gammal, M; Abdel-Hamid, M; Farooqi, I S; Amr, K

    2011-04-01

    Congenital deficiency of the leptin receptor is a very rare cause of severe early-onset obesity. To date, only 9 families have been reported in the literature to have mutations in the leptin receptor gene. The clinical features include severe early onset obesity, severe hyperphagia, hypogonadotropic hypogonadism, and T cell and neuroendocrine/metabolic dysfunction. Here we report two cousins with severe early onset obesity and recurrent respiratory tract infections. Their serum leptin levels were elevated but they were within the range predicted by the elevated fat mass in both cousins. Direct sequencing of the entire coding sequence of the leptin receptor gene revealed a novel homozygous missense mutation in exon 6, P316T. The mutation was found in the homozygous form in both cousins and in the heterozygote state in their parents. This mutation was not found in 200 chromosomes from 100 unrelated normal weight control subjects of Egyptian origin using PCR-RFLP analysis. In conclusion, finding this new mutation in the LEPR beside our previous mutation in the LEP gene implies that monogenic obesity syndromes may be common in the Egyptian population owing to the high rates of consanguineous marriages. Further screening of more families for mutations in LEP, LEPR, and MC4 might confirm this assumption. PMID:21306929

  20. Clinical and Molecular Studies Reveal a PSEN1 Mutation (L153V) in a Peruvian Family with Early-Onset Alzheimer's Disease

    PubMed Central

    Cornejo-Olivas, Mario R.; Yu, Chang-En; Mazzetti, Pilar; Mata, Ignacio F.; Meza, Maria; Lindo-Samanamud, Saul; Leverenz, James B.; Bird, Thomas D.

    2014-01-01

    Presenilin 1 (PSEN1) gene mutations are found in 30 to 70% of familial early onset Alzheimer disease (EOAD) cases (onset <60 years). Prevalence of these mutations is highly variable including ethnic differences worldwide. No Peruvian kindred with familial AD (FAD) have been described. Standardized clinical evaluation and cognitive assessment was completed in a Peruvian family with severe EOAD. Clinical course was characterized by very early onset (before age 35 years), progressive cognitive impairment with early memory loss, spatial disorientation and executive dysfunction. We sequenced all exons of PSEN1 in the proband and identified a c.475C>G DNA change resulting in a p.L153V missense mutation in the transmembrane domain 2 of the gene. This mutation is also present in the three additional affected siblings but not in a non-affected family member consistent with segregation of this mutation with the disease. This is the first report of a Peruvian family affected with EOAD associated with a PSEN1 mutation. This same mutation has been reported previously in English and French families, but a novel variants very close to the mutation and ancestry informative markers analysis suggests the mutation might be of Amerindian or African origin in this Peruvian family. PMID:24495933

  1. A rare case of early onset type of abdominal trocar site hernia (TSH) with atypical externalizing in two-step: multidetector row CT diagnosis.

    PubMed

    Coulier, B; Ramboux, A; Pierard, F

    2014-01-01

    We report a rare case of early onset type Trocar Site Hernia (TSH) producing in the right lower abdominal quadrant of a 64-year old obese woman. The patient was admitted in the emergency room for abdominal pain producing four days after laparoscopic adnexectomy. The hernia atypically externalized in two-steps creating two superposed concentric small bowel strangulating hernias producing through two distinctive superposed orifices. A precise and complete anatomic diagnosis was made by contrast enhanced 64-row multidetector computed tomography (MDCT). The imaging features are presented with a short review of the literature. The case emphasizes the high performances of MDCT for the early diagnosis of Trocar Site Hernias. PMID:25597215

  2. A case-control study on risk factors for early-onset respiratory tract infection in patients admitted in ICU

    PubMed Central

    Cardoso, Teresa C; Lopes, Luís M; Carneiro, António H

    2007-01-01

    Background Respiratory tract infections are common in intensive care units (ICU), with incidences reported from 10 to 65%, and case fatality rates over 20% in pneumonia. This study was designed to identify risk factors for the development of an early onset respiratory tract infection (ERI) and to review the microbiological profile and the effectiveness of first intention antibiotic therapy. Methods Case-control, retrospective clinical study of the patients admitted to the Intensive Care Unit (ICU) of our hospital, a teaching and tertiary care facility, from January to September 2000 who had a respiratory tract infection diagnosed in the first 5 days of hospital stay. Results Of the 385 patients admitted to our unit: 129 (33,5%) had a diagnosis of ERI and 86 patients were admitted to the control group. Documented aspiration (adjusted OR = 5,265; 95% CI = 1,155 – 24,007) and fractured ribs (adjusted OR = 12,150; 95% CI = 1,571 – 93,941) were found to be independent risk factors for the development of ERI (multiple logistic regression model performed with the diagnostic group as dependent variable and adjusted for age, sex, SAPS II, documented aspiration, non-elective oro-tracheal intubation (OTI), fractured ribs, pneumothorax and pleural effusion). A total of 78 organisms were isolated in 61 patients (47%). The normal flora of the upper airway (Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenza and Moraxella catharralis) accounted for 72% of all isolations achieved, polimicrobian infections were responsible for 25% of all microbiological documented infections. First intention treatment was, in 62% of the patients, the association amoxacillin+clavulanate, being effective in 75% of the patients to whom it was administered. The patients with ERI needed more days of OTI (6 vs 2, p < 0,001) and mechanical ventilation (6 vs 2, p < 0,001) and had a longer ICU (7 vs 2, p < 0,001) and hospital length of stay (17 vs 11, p = 0,018), when compared with controls. Conclusion In this study documented tracheobronchial aspiration and fractured ribs were identified as independent risk factors for ERI. Microbiological profile was dominated by sensitive micro-organisms. The choice amoxacilin+clavulanate revealed to be a good option with an effectiveness rate of 77% in the patients in whom it was used. PMID:17888157

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

    PubMed Central

    Al-Kadri, Hanan M; Bamuhair, Samira S; Johani, Sameera M Al; Al-Buriki, Namsha A; Tamim, Hani M

    2013-01-01

    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 regression has identified three risk factors that were associated with the highest tendency for the development of EOGBS disease. These were lack of antenatal attendance (OR =0.30 and CI 0.98–0.88), rupture of membranes (OR =9.62 and CI 3.1–29.4), and antibiotic use in labor (OR =0.16 and CI 0.38–0.67). Conclusion A number of maternal risk factors were significantly associated with EOGBS disease. Taking these factors into consideration may result in preventing the occurrence of EOGBS disease, improve maternal and neonatal medical care, decrease their hospital stay, and reduce unnecessary hospital resource utilization. PMID:24194650

  4. Manganese exposure among smelting workers: Relationship between blood manganese–iron ratio and early onset neurobehavioral alterations

    PubMed Central

    Cowan, Dallas M.; Zheng, Wei; Zou, Yan; Shi, Xiujuan; Chen, Jian; Rosenthal, Frank S.; Fan, Qiyuan

    2014-01-01

    A biomarker for detection of early onset neurobehavioral alterations in manganism remains unknown. The purpose of this study was to use a neurobehavioral test battery to identify subtle changes in Mn-induced motor and memory dysfunction and to relate the quantifiable neurological dysfunction to an established Mn-exposure index such as blood manganese–iron ratio (MIR). A total of 323 subjects were recruited to control (n = 106), low-exposure (122), and high-exposure (95) groups. The test battery consisted of standard testing procedures including the nine-hole and groove-type steadiness tester, Benton visual retention test, and Purdue pegboard coordination test. No significant health problems or clinically diagnosed neurological dysfunctions were observed. Benton test did not reveal any abnormal memory deficits among Mn-exposed smelters, nor did the groove and nine-hole tests detect any abnormality in dynamic and static steadiness in tested subjects. Purdue pegboard test showed a remarkable age-related decline in fine movement coordination among all study participants regardless of the Mn-exposure condition. Mn exposure significantly exacerbated this age-related deterioration. Statistical modeling revealed that the plasma and erythrocyte MIR (i.e., pMIR and eMIR, respectively) were associated with Purdue pegboard scores. Among all subjects whose MIR were above the cut-off value (COV), pMIR was significantly correlated with pegboard scores (r = ?0.261, p = 0.002), whereas for those subjects over the age of 40, the eMIR, but not pMIR, was associated with declined pegboard performance (r = ?0.219, p = 0.069). When both factors were taken into account (i.e., age > 40 and MIR > the COV), only pMIR was inversely associated with pegboard scores. Combining their usefulness in Mn-exposure assessment, we recommend that the blood Mn–Fe ratio may serve as a reasonable biomarker not only for assessment of Mn exposure but also for health risk assessment. PMID:19963104

  5. Can socioeconomic trajectories during the life influence periodontal disease occurrence in adulthood? Hypotheses from a life-course perspective.

    PubMed

    S Schuch, H; G Peres, K; G Do, L; Peres, M A

    2015-06-01

    Chronic periodontal disease (CPD) is a highly prevalent, multifactorial, bacterially induced inflammatory disease, characterized by pathologic loss of periodontal attachment and alveolar bone with onset mostly in adulthood. While cross-sectional data have demonstrated significant associations between adverse socioeconomic position (SEP) and poor periodontal conditions, there is a gap in the literature on the understanding of how SEPs in different life stages impact on the occurrence of this disease later on. Life-course epidemiology offers different theoretical models to study the pathway of health and illness during the lifespan, and the hypothesis of the present study is that the relationship between SEP and CPD can be explained based on different life-course epidemiology theories: (a) critical period model; (b) critical period with modifier effect model; (c) accumulation of risk model; (d) chain-of-risk model. Under the first theoretical model, the association between SEP and CPD may be explained by an inflammatory hypothesis, considering that childhood adverse socioeconomic backgrounds alter the immunoinflammatory response that leads to disease in adulthood regardless of conditions later in life. The second model postulates that the early life SEP modifies the host immunoinflammatory response, and the risk of disease will be modified over the life-course by socio-behavioural influences. The third, "accumulation of risk model", may explain such relationship taking into account exposures during different periods of life. However, this model does not consider the moment when the exposure occurred, only taking into consideration the number of episodes during the life cycle. Finally, the potential explanation to the role of socioeconomic position on chronic periodontal disease, using a chain-of-risk model, is that early low SEP may cause social stress related to social hierarchies, what may, in turn, trigger endocrine, neural and immune changes, that reflect on elevated levels of cytokines, consequently turning these individuals more likely to develop periodontal disease. To summarize, this paper suggests potential explanations of the relationship between SEP during the lifespan and the occurrence of chronic periodontal disease in adult life, under a life-course framework. Longitudinal studies focusing on such relationship should be conducted, aiming to provide evidence regarding the hypotheses here called in question. PMID:25801483

  6. Increasing age at symptom onset is associated with worse radiological damage at presentation in patients with early inflammatory polyarthritis

    PubMed Central

    Bukhari, Marwan; Lunt, Mark; Barton, Anne; Bunn, Dianne; Silman, Alan; Symmons, Deborah

    2007-01-01

    Background Increasing age at onset has been associated with worse outcome in rheumatoid arthritis, although there are few data from unselected inception cohorts. Hypothesis Increasing age is associated with a higher risk of erosions at presentation, and this increase is not explained by age?related disease confounders. Subjects and methods 222 subjects (median onset age 59?years) were studied from a primary?care?based register of new?onset inflammatory polyarthritis. Patients had hand and feet radiographs taken within 12?months from symptom onset. Films were scored by two readers using the Larsen score. The risk of erosions in those aged 50–69 and ?70?years at onset was compared with the risk in those aged <50?years both before and after adjustment for possible age?related disease confounders. Result The prevalences of erosions were 22%, 52% and 71% in those aged <50, 50–69 and ?70?years at onset equivalent to odds ratios (ORs) (95% confidence intervals (CIs)) of 3.5 (2.2 to 5.7) and 7.4 (4.5 to 12.1), respectively, in the two older age groups. Excluding those with proximal interphalangeal (PIP) erosions alone (due to possible osteoarthritis) did not alter these findings. Adjustments for disease characteristics using logistic regression did not attenuate these findings: adjusted ORs (95% CIs) 3.6 (2.1 to 6.1) and 6.9 (3.8 to 12.2) for age groups 50–69 and ?70?years, respectively. The influence of age was stronger than most of the disease?related variables in predicting erosions in this cohort. Conclusion Increasing age at symptom onset is strongly associated with higher occurrence of erosions within the first year unexplained by greater disease severity. PMID:16950810

  7. Amplified somatosensory and visual cortical projections to a core auditory area, the anterior auditory field, following early- and late-onset deafness.

    PubMed

    Wong, Carmen; Chabot, Nicole; Kok, Melanie A; Lomber, Stephen G

    2015-09-01

    Cross-modal reorganization following the loss of input from a sensory modality can recruit sensory-deprived cortical areas to process information from the remaining senses. Specifically, in early-deaf cats, the anterior auditory field (AAF) is unresponsive to auditory stimuli but can be activated by somatosensory and visual stimuli. Similarly, AAF neurons respond to tactile input in adult-deafened animals. To examine anatomical changes that may underlie this functional adaptation following early or late deafness, afferent projections to AAF were examined in hearing cats, and cats with early- or adult-onset deafness. Unilateral deposits of biotinylated dextran amine were made in AAF to retrogradely label cortical and thalamic afferents to AAF. In early-deaf cats, ipsilateral neuronal labeling in visual and somatosensory cortices increased by 329% and 101%, respectively. The largest increases arose from the anterior ectosylvian visual area and the anterolateral lateral suprasylvian visual area, as well as somatosensory areas S2 and S4. Consequently, labeling in auditory areas was reduced by 36%. The age of deafness onset appeared to influence afferent connectivity, with less marked differences observed in late-deaf cats. Profound changes to visual and somatosensory afferent connectivity following deafness may reflect corticocortical rewiring affording acoustically deprived AAF with cross-modal functionality. J. Comp. Neurol. 523:1925-1947, 2015 © 2015 Wiley Periodicals, Inc. PMID:25764419

  8. Temperature-dependent structural and functional properties of a mutant (F71L) ?A-crystallin: molecular basis for early onset of age-related cataract.

    PubMed

    Validandi, Vakdevi; Reddy, V Sudhakar; Srinivas, P N B S; Mueller, Niklaus H; Bhagyalaxmi, S G; Padma, T; Petrash, J Mark; Reddy, G Bhanuprakash

    2011-12-15

    Previously we identified a novel mutation (F71L) in the ?A-crystallin gene associated with early onset of age-related cataract. However, it is not known how the missense substitution translates into reduced chaperone-like activity (CLA), and how the structural and functional changes lead to early onset of the disease. Herein, we show that under native conditions the F71L-mutant is not significantly different from wild-type with regard to secondary and tertiary structural organization, hydrophobicity and the apparent molecular mass of oligomer but has substantial differences in structural and functional properties following a heat treatment. Wild-type ?A-crystallin demonstrated increased CLA, whereas the F71L-mutant substantially lost its CLA upon heat treatment. Further, unlike the wild-type ?A-subunit, F71L-subunit did not protect the ?B-subunit in hetero-oligomeric complex from heat-induced aggregation. Moreover, hetero-oligomer containing F71L and ?B in 3:1 ratio had significantly lower CLA upon thermal treatment compared to its unheated control. These results indicate that ?-crystallin complexes containing F71L-?A subunits are less stable and have reduced CLA. Therefore, F71L may lead to earlier onset of cataract due to interaction with several environmental factors (e.g., temperature in this case) along with the aging process. PMID:22085609

  9. Temperature-dependent structural and functional properties of a mutant (F71L) ?A-crystallin: Molecular basis for early onset of age-related cataract

    PubMed Central

    Validandi, Vakdevi; Reddy, V. Sudhakar; Srinivas, P.N.B.S.; Mueller, Niklaus H.; Bhagyalaxmi, S.G.; Padma, T.; Petrash, J. Mark; Reddy, G. Bhanuprakash

    2014-01-01

    Previously we identified a novel mutation (F71L) in the ?A-crystallin gene associated with early onset of age-related cataract. However, it is not known how the missense substitution translates into reduced chaperone-like activity (CLA), and how the structural and functional changes lead to early onset of the disease. Herein, we show that under native conditions the F71L-mutant is not significantly different from wild-type with regard to secondary and tertiary structural organization, hydrophobicity and the apparent molecular mass of oligomer but has substantial differences in structural and functional properties following a heat treatment. Wild-type ?A-crystallin demonstrated increased CLA, whereas the F71L-mutant substantially lost its CLA upon heat treatment. Further, unlike the wild-type ?A-subunit, F71L-subunit did not protect the ?B-subunit in hetero-oligomeric complex from heat-induced aggregation. Moreover, hetero-oligomer containing F71L and ?B in 3:1 ratio had significantly lower CLA upon thermal treatment compared to its unheated control. These results indicate that ?-crystallin complexes containing F71L-?A subunits are less stable and have reduced CLA. Therefore, F71L may lead to earlier onset of cataract due to interaction with several environmental factors (e.g., temperature in this case) along with the aging process. PMID:22085609

  10. Management of the neonate at risk for early-onset Group B streptococcal disease (GBS EOD): new paediatric guidelines in Belgium.

    PubMed

    Mahieu, L; Langhendries, J-P; Cossey, V; De Praeter, C; Lepage, P; Melin, P

    2014-10-01

    Despite group B streptococcal (GBS) screening in late pregnancy and intrapartum antimicrobial prophylaxis, early-onset sepsis in neonates remains a common source of neonatal morbidity and mortality especially in preterm neonates. The identification of neonates with early-onset sepsis is usually based on perinatal risk factors. Clinical signs are aspecific and laboratory tests are not sensitive. Therefore, many clinicians will overtreat at-risk infants. Inappropriate treatment with antibiotics increases the risk for late-onset sepsis, necrotizing enterocolitis, mortality, and prolongs hospitalisation and costs. In 2003, the Belgian Health Council published guidelines for the prevention of perinatal GBS infections. This report presents the Belgian paediatric management guidelines, which have been endorsed by the Belgian and Flemish societies of neonatology and paediatrics. The most imported changes in the 2014 guidelines are the following: recommendations for a lumbar puncture; clarification of normal spinal fluid parameters and blood neutrophil indices corrected for gestation age; specific timing for diagnostic testing after birth; no indication for diagnostic testing in asymptomatic newborns unless additional risk factors; a revised algorithm for management of neonates according to maternal and neonatal risk factors; and premature infants described as those below 35 weeks instead of 37 weeks. The guidelines were made on the basis of the best evidence and on expert opinion when inadequate evidence exists. PMID:25056493

  11. Genome-wide scan for genes involved in bipolar affective disorder in 70 European families ascertained through a bipolar type I early-onset proband: supportive evidence for linkage at 3p14

    Microsoft Academic Search

    B Etain; F Mathieu; M Rietschel; W Maier; M Albus; P McKeon; S Roche; C Kealey; D Blackwood; W Muir; F Bellivier; C Henry; C Dina; S Gallina; H Gurling; A Malafosse; M Preisig; F Ferrero; S Cichon; J Schumacher; S Ohlraun; M Borrmann-Hassenbach; P Propping; R Abou Jamra; T G Schulze; A Marusic; Z M Dernovsek; B Giros; T Bourgeron; A Lemainque; D Bacq; C Betard; C Charon; M M Nöthen; M Lathrop; M Leboyer

    2006-01-01

    Preliminary studies suggested that age at onset (AAO) may help to define homogeneous bipolar affective disorder (BPAD) subtypes. This candidate symptom approach might be useful to identify vulnerability genes. Thus, the probability of detecting major disease-causing genes might be increased by focusing on families with early-onset BPAD type I probands. This study was conducted as part of the European Collaborative

  12. [Periodontal diseases, tobacco and pregnancy].

    PubMed

    Boutigny, H; Boschin, F; Delcourt-Debruyne, E

    2005-04-01

    This review summarizes the impact of tobacco on the periodontium of pregnant women and the effects of periodontal diseases combined with tobacco on the pregnancy. Periodontal diseases (gingivitis and periodontitis) are gram-negative anaerobic infections. Smokers are 2-7 times more likely to develop periodontal disease than non-smokers. Tobacco, an environmental factor, undermines the host response and may facilitate the development and progression of periodontal disease. Recent epidemiological studies suggest that maternal periodontal diseases would be a risk factor of pre-term deliveries or pre-term low birth weight (PLBW). Cigarette smoking during pregnancy leads to peri-natal morbidity and mortality and it is associated with reduced birth-weight. Tobacco during pregnancy also amplifies the risk of PLBW directly and via periodontal diseases. This article highlights the etio-pathogenic interrelations between periodontal diseases and tobacco as risk factors of PLBW. The blood dissemination of periodontal bacteria and the effects of cytokines like TNF-alpha, Il-1, produced during periodontal infections could explain these obstetrical adverse events. The concept of diagnosing and treating a periodontal disease in a pregnant woman to minimizes the deleterious effects of this infection on systemic conditions represents an unprecedented challenge. Moreover, periodontist have the opportunity to take part in smoking cessation program for pregnant women. PMID:15980775

  13. Preliminary evidence for an association of a dinucleotide repeat polymorphism at the MAOA gene with early onset alcoholism/substance abuse

    SciTech Connect

    Vanyukov, M.M.; Moss, H.B.; Tarter, R.E. [Univ. of Pittsburg, PA (United States)] [and others

    1995-04-24

    An association between the liability to early onset alcoholism/substance abuse and a recently discovered dinucleotide repeat length polymorphism at the MAOA gene (MAOCA-1) was examined using polymerase chain reaction (PCR). A significant correlation between the presence/absence of the disorder and the length of the MAOCA-1 repeat was found in males, but not females, with {open_quotes}long{close_quotes} alleles (repeat length above 115 bp) associated with both increased risk for the disorder and lower age of onset of substance abuse. These preliminary data suggest that further exploration of the relationship between the MAOA gene and behavioral traits in an expanded sample is warranted. 22 refs., 1 fig., 3 tabs.

  14. Genetics of recurrent early-onset depression (GenRED): design and preliminary clinical characteristics of a repository sample for genetic linkage studies.

    PubMed

    Levinson, Douglas F; Zubenko, George S; Crowe, Raymond R; DePaulo, Raymond J; Scheftner, William S; Weissman, Myrna M; Holmans, Peter; Zubenko, Wendy N; Boutelle, Sandra; Murphy-Eberenz, Kathleen; MacKinnon, Dean; McInnis, Melvin G; Marta, Diana H; Adams, Philip; Sassoon, Stephanie; Knowles, James A; Thomas, Jo; Chellis, Jennifer

    2003-05-15

    This is an initial report on a six-site collaborative project, Genetics of Recurrent Early-Onset Depression (GenRED). This is a study of a large sample of families with recurrent major depressive disorder (DSM-IV) beginning by the age 30 in probands or 40 in relatives. Evidence suggests that early onset and recurrence of depressive episodes predict substantially increased risk of depression in first-degree relatives compared with the general population, suggesting that susceptibility genes might be mapped with this phenotype. The projected sample of 800-1,000 affected sibling pairs (ASPs) and other relatives will be studied using genome scan methods. Biological materials and blinded clinical data will be made available through the NIMH cell repository program. The sample should have good-to-excellent power to detect a locus associated with a 24% or greater population-wide increase in risk to siblings. We describe 838 affected individuals from the first 305 families containing 434 independent ASPs, or 613 ASPs counting all possible pairs. The mean age at the onset was 18.5 years, with a mean of 7.3 episodes and longest episode of 655 days. Almost all subjects had experienced at least 4 weeks of depression with five or more additional symptom criteria. Frequencies of symptoms and psychiatric and medical comorbid are provided. Substance use was more common in males, and panic disorder in females. Within pairs of affected siblings, correlations were significant for age at onset, substance abuse/dependence, panic disorder, obsessive-compulsive disorder and nicotine initiation and persistence. We replicated previously reported associations among comorbid panic disorder and social phobia, chronicity of depression and suicidal behavior. This suggests comparability of our cases to those in earlier large family studies. This dataset should prove useful for genetic studies of a highly familial form of major depressive disorder. PMID:12707949

  15. Early onset of PRES in a patient with a subarachnoid haemorrhage due to a ruptured intracranial aneurysm.

    PubMed

    Kuroda, Hiroki; Kashimura, Hiroshi; Murakami, Toshiyuki; Endo, Hidehiko; Mase, Tomohiko; Ogasawara, Kuniaki

    2014-12-01

    Posterior reversible encephalopathy syndrome (PRES) is rarely associated with subarachnoid haemorrhage (SAH). We present a case involving a patient who developed PRES, prior to induction of hypertensive therapy, 2 days after the onset of a SAH due to a ruptured intracranial aneurysm. PMID:24799279

  16. Maternal markers for detecting early-onset neonatal infection and chorioamnionitis in cases of premature rupture of membranes at or after 34 weeks of gestation: a two-center prospective study

    Microsoft Academic Search

    Thomas Popowski; François Goffinet; Françoise Maillard; Thomas Schmitz; Sandrine Leroy; Gilles Kayem

    2011-01-01

    Background  Accurate prediction of infection, including maternal chorioamnionitis and early-onset neonatal infection, remains a critical\\u000a challenge in cases of preterm rupture of membranes and may influence obstetrical management. The aim of our study was to investigate\\u000a the predictive value for early-onset neonatal infection and maternal histological and clinical chorioamnionitis of maternal\\u000a biological markers in routine use at or after 34 weeks

  17. An increased level of antibodies to ?-ltoglobulin is a risk determinant for early-onset Type 1 (insulin-dependent) diabetes mellitus independent of islet cell antibodies and early introduction of cow's milk

    Microsoft Academic Search

    G. Dahlquist; E. Savilahti; M. Landin-Olsson

    1992-01-01

    Summary  Using a case-control design we have studied whether antibodies to cow's milk proteins are risk determinants for childhood-onset Type 1 (insulin-dependent) diabetes mellitus independent of early exposure to cow's milk formula and islet cell antibodies. Sera from 116 recentonset diabetic children and 112 age- and sex- matched control children were analysed for cow's milk protein IgA, IgG and IgM antibodies,

  18. A longitudinal assessment of periodontal disease in 52 miniature schnauzers

    PubMed Central

    2014-01-01

    Background Periodontal disease (PD) is the most widespread oral disease in dogs and has been associated with serious systemic diseases. The disease is more prevalent in small breeds compared to large breeds and incidence increases with advancing age. In prevalence studies 84% of beagles over the age of 3 and 100% of poodles over the age of 4 were diagnosed with PD. Current knowledge of the rate of progression of PD is limited. The objective of this study was to determine the rate of PD progression in miniature schnauzers, an at risk small breed of dog. Dogs (n?=?52, age 1.3-6.9 years) who had received a regular oral care regime prior to this study were assessed for levels of gingivitis and periodontitis around the whole gingival margin in every tooth under general anaesthetic. Assessments were conducted approximately every six weeks for up to 60 weeks following the cessation of the oral care regime. Results All of the 2155 teeth assessed entered the study with some level of gingivitis. 23 teeth entered the study with periodontitis, observed across 12 dogs aged between 1.3 and 6.9 years. 35 dogs had at least 12 teeth progress to periodontitis within 60 weeks. Of the teeth that progressed to periodontitis, 54% were incisors. The lingual aspect of the incisors was significantly more likely to be affected (p?periodontitis-affected teeth was variable with 24% of the aspects affected having very mild gingivitis, 36% mild gingivitis and 40% moderate gingivitis. Periodontitis progression rate was significantly faster in older dogs. Only one dog (age 3.5) did not have any teeth progress to periodontitis after 60 weeks. Conclusions This is the first study to have assessed the progression rate of periodontitis in miniature schnauzers and highlights that with no oral care regime, the early stages of periodontitis develop rapidly in this breed. An oral care regime and twice yearly veterinary dental health checks should be provided from an early age for this breed and other breeds with similar periodontitis incidence rates. PMID:25179569

  19. Risk Factors for Long-term Outcome of Drug-eluting Stenting in Adults with Early-onset Coronary Artery Disease

    PubMed Central

    An, Guipeng; Du, Zhongqi; Meng, Xiao; Guo, Tao; Li, Guishuang; Chen, Yuguo; Li, Jifu; An, Fengshuang; Zhang, Yun; Li, Wenjing; Zhang, Cheng

    2014-01-01

    Objective We lack data on the long-term outcome of drug-eluting stenting in patients with early-onset coronary artery disease (CAD). Here, we investigated the association of traditional risk factors and major adverse cardiovascular events (MACEs) after drug-eluting stenting in patients with CAD who were < 50 years old. Methods We enrolled 437 consecutive CAD patients < 50 years old who underwent drug-eluting stenting and 132 subjects who were age- and sex-matched and angiographically shown to be disease free as controls. MACEs were analyzed in CAD patients for a median of 24 months [interquartile range 14-34 months]. Results Male patients accounted for 90.4% of cases. As compared with controls, patients with early-onset CAD had higher body mass index and rates of smoking, family history of CAD, and diabetes and hypercholesterolemia. During the hospital stay, 1 patient died, and the incidence of MACEs was 1.1%. At the end of follow-up, the overall death rate was 0.7%. MACEs were observed in 54 patients (12.4%). On Cox proportional hazard analyses, positive family history and diabetes were independent risk factors of MACEs (HR 2.61, 95% confidence interval 1.29-4.00, p = 0.002; and HR 2.48, 95% confidence interval 0.86-3.14, p = 0.004, respectively). Conclusions Drug-eluting stenting is a reliable treatment for patients with early-onset CAD. Positive family history of CAD and diabetes are independent risk factors of adverse cardiovascular events in this subgroup of patients after drug-eluting stent implantation. PMID:24904227

  20. BRCA1/BRCA2 gene mutations/SNPs and BRCA1 haplotypes in early-onset breast cancer patients of Indian ethnicity.

    PubMed

    Juwle, Abida; Saranath, Dhananjaya

    2012-12-01

    We examined BRCA1/2 mutations and single nucleotide polymorphisms (SNPs) for identification of BRCA1 haplotypes, in early-onset breast cancer patients and their relatives, sporadic breast cancer patients, and unrelated normal healthy females, of Indian ethnicity. Peripheral blood DNA was amplified by polymerase chain reaction, at BRCA1/2 coding exons and subject to nucleotide sequencing using ABI 3100 Genetic Analyzer. We observed BRCA1/BRCA2 mutations in 52 % early-onset breast cancer patients and in 57 % relatives. Deleterious mutations detected in early-onset patients and relatives were 187delAG, 632insT, 1052delT, Q759X, Q780X, R1203X, 5154delC, IVS14 + 1G > A, IVS17 + 1G > T, and 632insT in BRCA1 gene; and 4075delGT, 5076delAA, 6079delAGTT, and W3127X in BRCA2 gene. A high degree of penetrance of BRCA1/2 gene mutations was observed in the relatives. BRCA1/2 SNPs were identified in the Indian population, and association of BRCA1 haplotypes with breast cancer was investigated. A significantly increased frequency of the SNPs 203G/A, 3624A/G and 7470A/G SNPs in BRCA2 gene was observed in normal controls indicative of a protective effect of the SNPs. BRCA1 haplotype 2 was most frequently observed in our population. Our study indicates a high incidence of BRCA1/BRCA2 gene mutations in the Indian patients. The BRCA1/2 mutations and SNPs are detailed on our website http://relibrca.rellife.com . PMID:22752604

  1. Rheumatoid arthritis and periodontitis – inflammatory and infectious connections. Review of the literature

    PubMed Central

    Rutger Persson, G.

    2012-01-01

    An association between oral disease/periodontitis and rheumatoid arthritis (RA) has been considered since the early 1820s. The early treatment was tooth eradication. Epidemiological studies suggest that the prevalence of RA and periodontitis may be similar and about 5% of the population are aged 50 years or older. RA is considered as an autoimmune disease whereas periodontitis has an infectious etiology with a complex inflammatory response. Both diseases are chronic and may present with bursts of disease activity. Association studies have suggested odds ratios of having RA and periodontitis varying from 1.8:1 (95% CI: 1.0–3.2, NS) to 8:1 (95% CI: 2.9–22.1, p<0.001). Genetic factors are driving the host responses in both RA and periodontitis. Tumor necrosis factor-?, a proinflammatory cytokine, regulates a cascade of inflammatory events in both RA and periodontitis. Porphyromonas gingivalis is a common pathogen in periodontal infection. P. gingivalis has also been identified in synovial fluid. The specific abilities of P. gingivalis to citrullinate host peptides by proteolytic cleavage at Arg-X peptide bonds by arginine gingipains can induce autoimmune responses in RA through development of anticyclic citrullinated peptide antibodies. In addition, P. gingivalis carries heat shock proteins (HSPs) that may also trigger autoimmune responses in subjects with RA. Data suggest that periodontal therapies combined with routine RA treatments further improve RA status. Conclusions Periodontal infection (P. gingivalis) carries a unique risk for development of autoimmune antibodies associated with RA. Patients with RA have either lost many teeth or usually have severe periodontitis. Additional research, both in regards to basic mechanisms as well as clinical studies, are necessary before it can be said that there are causative links between RA and periodontitis. Cross-disciplinary research in well-defined populations should be performed to further enhance knowledge and develop clinical strategies how to coordinate therapy and risk assessments of RA and periodontitis. PMID:22347541

  2. Periodontics II: Course Proposal.

    ERIC Educational Resources Information Center

    Dordick, Bruce

    A proposal is presented for Periodontics II, a course offered at the Community College of Philadelphia to give the dental hygiene/assisting student an understanding of the disease states of the periodontium and their treatment. A standardized course proposal cover form is given, followed by a statement of purpose for the course, a list of major…

  3. Bacterial isolates of early-onset neonatal sepsis and their antibiotic susceptibility pattern between 1998 and 2004: an audit from a center in India

    Microsoft Academic Search

    Ramesh Bhat Y; Leslie Edward S Lewis; Vandana KE

    2011-01-01

    Background  Epidemiology and surveillance of neonatal sepsis helps in implementation of rational empirical antibiotic strategy.\\u000a \\u000a \\u000a \\u000a Objective  To study the frequency of bacterial isolates of early onset neonatal sepsis (EONS) and their sensitivity pattern.\\u000a \\u000a \\u000a \\u000a Methods  In this retrospective study, a case of EONS was defined as an infant who had clinical signs or born to mothers with potential\\u000a risk factors for infection, in whom

  4. Binge eating and fast cognitive worsening in an early-onset bvFTD patient carrying C9ORF72 expansion.

    PubMed

    Talarico, G; Canevelli, M; Tosto, G; Piscopo, P; Confaloni, A; Galimberti, D; Fenoglio, C; Scarpini, E; Gasparini, M; Bruno, G

    2015-10-01

    An expanded hexanucleotide (GGGGCC) repeat in a non-coding promoter region of open reading frame 72 of chromosome 9 (C9ORF72) has been recently identified as a major cause of familial and sporadic frontotemporal lobar degeneration. We describe the clinical picture of a 64-year-old woman carrying the hexanucleotide repeat expansion, who developed a sporadic early-onset form of behavioral variant frontotemporal dementia characterized by the occurrence of uncommon behavioral manifestations such as binge eating disturbance and by a rapid worsening of cognitive abilities. Our report confirms previous studies asserting that C9ORF72 repeats may sustain heterogeneous clinical syndromes. PMID:25158292

  5. Early Onset and Severe Clinical Course Associated with the m.5540G>A Mutation in MT-TW

    PubMed Central

    Granadillo, Jorge L.; Moss, Timothy; Lewis, Richard A.; Austin, Elise G.; Kelfer, Howard; Wang, Jing; Wong, Lee-Jun C.; Scaglia, Fernando

    2014-01-01

    We report a patient harboring a de novo m.5540G>A mutation affecting the MT-TW gene coding for the mitochondrial tryptophan-transfer RNA. This patient presented with atonic-myoclonic epilepsy, bilateral sensorineural hearing loss, ataxia, motor regression, ptosis, and pigmentary retinopathy. Our proband had an earlier onset and more severe phenotype than the first reported patient harboring the same mutation. We discuss her clinical presentation and compare it with the only previously published case. PMID:25302159

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

    PubMed

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

    2015-08-01

    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. PMID:25782704

  7. Saliva: A diagnostic biomarker of periodontal diseases

    PubMed Central

    Patil, Priti Basgauda; Patil, Basgauda Ramesh

    2011-01-01

    Early detection of disease plays a crucial role in successful therapy. Early diagnosis and management reduces the severity and possible complications of the disease process. To overcome this challenge, medical researchers are devoted to finding molecular disease biomarkers that reveal a hidden lethal threat before the disease becomes complicated. Saliva, an important physiologic fluid, containing a highly complex mixture of substances, is rapidly gaining popularity as a diagnostic tool. Periodontal disease is a chronic disease of the oral cavity comprising a group of inflammatory conditions affecting the supporting structures of the dentition. In the field of periodontology, traditional clinical criteria are often insufficient for determining sites of active disease, for monitoring the response to therapy, or for measuring the degree of susceptibility to future disease progression. Saliva, as a mirror of oral and systemic health, is a valuable source for clinically relevant information because it contains biomarkers specific for the unique physiologic aspects of periodontal diseases. This review highlights the various potentials of saliva as a diagnostic biomarker for periodontal diseases. PMID:22368352

  8. A Homozygous Mutation in LYRM7/MZM1L Associated with Early Onset Encephalopathy, Lactic Acidosis, and Severe Reduction of Mitochondrial Complex III Activity

    PubMed Central

    Invernizzi, Federica; Tigano, Marco; Dallabona, Cristina; Donnini, Claudia; Ferrero, Ileana; Cremonte, Maurizio; Ghezzi, Daniele; Lamperti, Costanza; Zeviani, Massimo

    2013-01-01

    Mutations in nuclear genes associated with defective complex III (cIII) of the mitochondrial respiratory chain are rare, having been found in only two cIII assembly factors and, as private changes in single families, three cIII structural subunits. Recently, human LYRM7/MZM1L, the ortholog of yeast MZM1, has been identified as a new assembly factor for cIII. In a baby patient with early onset, severe encephalopathy, lactic acidosis and profound, isolated cIII deficiency in skeletal muscle, we identified a disease-segregating homozygous mutation (c.73G>A) in LYRM7/MZM1L, predicting a drastic change in a highly conserved amino-acid residue (p.Asp25Asn). In a mzm1? yeast strain, the expression of a mzm1D25N mutant allele caused temperature-sensitive respiratory growth defect, decreased oxygen consumption, impaired maturation/stabilization of the Rieske Fe–S protein, and reduced complex III activity and amount. LYRM7/MZM1L is a novel disease gene, causing cIII-defective, early onset, severe mitochondrial encephalopathy. PMID:24014394

  9. Low Copy Number of the AMY1 Locus Is Associated with Early-Onset Female Obesity in Finland

    PubMed Central

    Armenio, Miriam; Pekkinen, Minna; Pettersson, Maria; Valta, Helena; Lipsanen-Nyman, Marita; Mäkitie, Outi; Lindstrand, Anna

    2015-01-01

    Background The salivary ?-amylase locus (AMY1) is located in a highly polymorphic multi allelic copy number variable chromosomal region. A recent report identified an association between AMY1 copy numbers and BMI in common obesity. The present study investigated the relationship between AMY1 copy number, BMI and serum amylase in childhood-onset obesity. Patients Sixty-one subjects with a history of childhood-onset obesity (mean age 19.1 years, 54% males) and 71 matched controls (19.8 yrs, 45% males) were included. All anthropometric measures were greater in the obese; their mean BMI was 40 kg/m2 (range 25-62 kg/m2) compared with 23 kg/m2 in the controls (15-32 kg/m2). Results Mean AMY1 copy numbers did not differ between the obese and control subjects, but gender differences were observed; obese men showed the highest and obese women the lowest number of AMY1 copies (p=0.045). Further, only in affected females, AMY1 copy number correlated significantly with whole body fat percent (r=-0.512, p=0.013) and BMI (r=-0.416, p=0.025). Finally, a clear linear association between AMY1 copy number and serum salivary amylase was observed in all subgroups but again differences existed between obese males and females. Conclusions In conclusion, our findings suggest that AMY1 copy number differences play a role in childhood-onset obesity but the effect differs between males and females. Further studies in larger cohorts are needed to confirm these observations. PMID:26132294

  10. Early onset and enhanced growth of autochthonous mammary carcinomas in C3-deficient Her2/neu transgenic mice

    PubMed Central

    Bandini, Silvio; Curcio, Claudia; Macagno, Marco; Quaglino, Elena; Arigoni, Maddalena; Lanzardo, Stefania; Hysi, Albana; Barutello, Giuseppina; Consolino, Lorena; Longo, Dario Livio; Musiani, Piero; Forni, Guido; Iezzi, Manuela; Cavallo, Federica

    2013-01-01

    Aside from its classical role in fighting infections, complement is an important, although poorly understood, component of the tumor microenvironment. In particular, the tumor growth-regulatory activities of complement remain under debate. To assess the role of the complement system in the progression of autochthonous mammary carcinomas, we have crossed complement component 3 (C3)-deficient (C3?/?) BALB/c male mice with BALB/c females expressing the activated rat Her2/neu oncogene (neuT). Although neuT transgenic mice develop spontaneous mammary cancers with 100% penetrance, a significantly shorter tumor latency (i.e., earlier onset of the first palpable tumor), a higher frequency of multiple tumors (multiplicity), and a dramatic increase in the tumor growth rate were found in neuT-C3?/? animals. The accelerated tumor onset observed in neuT-C3?/? mice was paralleled by an earlier onset of spontaneous lung metastases and by an increase in Her2 expression levels, primarily on the surface of tumor cells. The percentage of immune cells infiltrating neuT carcinomas was similar in C3-deficient and C3-proficient mice, with the exception of a significant increase in the frequency of regulatory T cells in neuT-C3?/? tumors. Of particular interest, the enhanced immunosuppression imparted by C3 deficiency clearly influenced the immunogenic phenotype of autochthonous mammary tumors as neuT-C3?/? malignant cells transplanted into syngeneic immunocompetent hosts gave rise to lesions with a significantly delayed kinetics and reduced incidence as compared with cells obtained from neuT C3-proficient tumors. Finally, increased blood vessel permeability was evident in neuT-C3?/? tumors, although a similar number of tumor vessels was found in neuT and neuT-C3?/? lesions. Altogether, these data suggest that complement plays a crucial role in the immunosurveillance and, possibly, the immunoediting of Her2-driven autochthonous mammary tumors. PMID:24228231

  11. Periodontal Disease and Systemic Health

    MedlinePLUS

    ... Gum Disease Regenerative Procedures Dental Crown Lengthening Procedure Dental Implants Single Tooth Implants Multiple Tooth Implants Full Mouth Dental Implants Sinus Augmentation Ridge Modification Periodontal Pocket Reduction Procedures ...

  12. Role of salivary matrix metalloproteinase-8 (MMP-8) in chronic periodontitis diagnosis.

    PubMed

    Gupta, Namita; Gupta, N D; Gupta, Akash; Khan, Saif; Bansal, Neha

    2015-03-01

    Periodontitis is an inflammatory disease of the periodontium. Any imbalance between the matrix metalloproteinases (MMPs) secreted by neutrophils and tissue inhibitors initiates the destruction of collagen in gum tissue, leading to chronic periodontitis. This study aimed to correlate salivary levels of MMP-8 and periodontal parameters of chronic periodontitis to establish MMP-8 as a noninvasive marker for the early diagnosis of chronic periodontitis. The study involved 40 subjects visiting the periodontic OPD of Dr. Ziauddin Ahmad Dental College and Hospital, located in Aligarh, U.P., India, from 2011 to 2012. The subjects were divided into two groups: group I consisted of 20 periodontally healthy subjects (controls) while group II consisted of 20 patients with chronic periodontitis. Chronic periodontitis was assessed on the basis of several periodontal parameters, including pocket probing depth (PPD), clinical attachment level (CAL), gingival index (GI), and plaque index (PI). Around 3ml of unstimulated and whole expectorated saliva was collected for MMP-8 estimation by ELISA using Quantikine human total MMP-8 immunoassay kits. Data were analyzed using STATISTICA (Windows version 6) software. Salivary MMP-8 levels of groups I and II were 190.91 ± 143.89 ng/ml and 348.26 ± 202.1 ng/ml, respectively. The MMP-8 levels and periodontal status (PPD, CAL, GI, and PI) of groups I and II showed positive and significant correlations (for PPD, r = 0.63, P < 0.001; for CAL, r = 0.54, P < 0.001; for GI, r = 0.49, P < 0.001; and for PI, r = 0.63, P < 0.001). The results of this study demonstrate elevated concentrations of MMP-8 in individuals with chronic periodontitis. PMID:25098434

  13. Lasers in periodontics

    PubMed Central

    Elavarasu, Sugumari; Naveen, Devisree; Thangavelu, Arthiie

    2012-01-01

    Laser is one of the most captivating technologies in dental practice since Theodore Maiman in 1960 invented the ruby laser. Lasers in dentistry have revolutionized several areas of treatment in the last three and a half decades of the 20th century. Introduced as an alternative to mechanical cutting device, laser has now become an instrument of choice in many dental applications. Evidence suggests its use in initial periodontal therapy, surgery, and more recently, its utility in salvaging implant opens up a wide range of applications. More research with better designs are a necessity before lasers can become a part of dental armamentarium. This paper gives an insight to laser in periodontics. PMID:23066266

  14. A Large Number of Protein Expression Changes Occur Early in Life and Precede Phenotype Onset in a Mouse Model for Huntington Disease*S?

    PubMed Central

    Zabel, Claus; Mao, Lei; Woodman, Ben; Rohe, Michael; Wacker, Maik A.; Kläre, Yvonne; Koppelstätter, Andrea; Nebrich, Grit; Klein, Oliver; Grams, Susanne; Strand, Andrew; Luthi-Carter, Ruth; Hartl, Daniela; Klose, Joachim; Bates, Gillian P.

    2009-01-01

    Huntington disease (HD) is fatal in humans within 15–20 years of symptomatic disease. Although late stage HD has been studied extensively, protein expression changes that occur at the early stages of disease and during disease progression have not been reported. In this study, we used a large two-dimensional gel/mass spectrometry-based proteomics approach to investigate HD-induced protein expression alterations and their kinetics at very early stages and during the course of disease. The murine HD model R6/2 was investigated at 2, 4, 6, 8, and 12 weeks of age, corresponding to absence of disease and early, intermediate, and late stage HD. Unexpectedly the most HD stage-specific protein changes (71–100%) as well as a drastic alteration (almost 6% of the proteome) in protein expression occurred already as early as 2 weeks of age. Early changes included mainly the up-regulation of proteins involved in glycolysis/gluconeogenesis and the down-regulation of the actin cytoskeleton. This suggests a period of highly variable protein expression that precedes the onset of HD phenotypes. Although an up-regulation of glycolysis/gluconeogenesis-related protein alterations remained dominant during HD progression, late stage alterations at 12 weeks showed an up-regulation of proteins involved in proteasomal function. The early changes in HD coincide with a peak in protein alteration during normal mouse development at 2 weeks of age that may be responsible for these massive changes. Protein and mRNA data sets showed a large overlap on the level of affected pathways but not single proteins/mRNAs. Our observations suggest that HD is characterized by a highly dynamic disease pathology not represented by linear protein concentration alterations over the course of disease. PMID:19043139

  15. Conjugated linoleic Acid supplementation during pregnancy and lactation reduces maternal high-fat-diet-induced programming of early-onset puberty and hyperlipidemia in female rat offspring.

    PubMed

    Reynolds, Clare M; Segovia, Stephanie A; Zhang, Xiaohuan D; Gray, Clint; Vickers, Mark H

    2015-02-01

    A maternal high-fat (HF) diet during pregnancy and lactation can result in adverse metabolic and reproductive outcomes in female offspring independent of postnatal diet. Interventions during critical windows of developmental plasticity may prevent developmental programming in offspring. The effects of maternal supplementation with the anti-inflammatory lipid conjugated linoleic acid (CLA) on early-onset puberty, metabolic dysfunction, and estrous cycle dysfunction was assessed. Sprague-Dawley rats were randomly assigned to a purified control diet (CD; 10% kcal from fat), CD with CLA (CLA; 10% kcal from fat, 1% CLA), HF (45% kcal from fat) or HF with CLA (HFCLA; 45% kcal from fat, 1% CLA). Diets were fed ad libitum for 10 days prior to time mating and throughout gestation and lactation. Offspring plasma/tissues were taken at Day 24 (prepubertal) or Day 150 (adult). Puberty was assessed from Day 26 and estrous cycle from Day 128. Female offspring from HF mothers had lower birth weights but by Postnatal Day 24 had exhibited catch-up growth concomitant with increased fat mass, hyperleptinemia, and dyslipidemia. Maternal CLA supplementation reversed these effects. Early-onset puberty was only observed in HF offspring; this was reversed in HFCLA offspring. In adulthood, despite no evidence of glucose intolerance or altered insulin sensitivity, HF offspring displayed increased fat mass, dyslipidemia, disrupted estrous cyclicity. and hyperleptinemia; this was reversed by maternal CLA supplementation. Data presented in this study demonstrate the importance of diet in women of reproductive age and during pregnancy on reproductive and metabolic parameters in their offspring and that supplementation with CLA during critical windows of development may represent a therapeutic strategy in the prevention of early-life programming of metabolic and reproductive dysfunction. PMID:25505197

  16. A new Mdr2(-/-) mouse model of sclerosing cholangitis with rapid fibrosis progression, early-onset portal hypertension, and liver cancer.

    PubMed

    Ikenaga, Naoki; Liu, Susan B; Sverdlov, Deanna Y; Yoshida, Shuhei; Nasser, Imad; Ke, Qingen; Kang, Peter M; Popov, Yury

    2015-02-01

    We previously characterized the Mdr2(Abcb4)(-/-) mouse as a reproducible model of chronic biliary liver disease. However, it demonstrates relatively slow fibrosis progression, possibly due to its fibrosis-resistant genetic background. We aimed to improve the model by moving it onto a fibrosis-susceptible background. We generated novel BALB/c.Mdr2(-/-) mouse via genetic backcross onto highly fibrosis-susceptible BALB/c substrain, identified in inbred mouse strain screening. Liver fibrosis, portal pressure, and hepatic tumor burden in BALB/c.Mdr2(-/-) mice were studied up to 1 year of age in direct comparison to parental strain FVB.Mdr2(-/-). BALB/c.Mdr2(-/-) mice developed periductular onion-skin type fibrotic lesions and pronounced ductular reaction starting from 4 weeks of age. Compared to parental strain, BALB/c.Mdr2(-/-) mice demonstrated dramatically accelerated liver fibrosis, with threefold increase in collagen deposition and bridging fibrosis/early signs of cirrhosis at 12 weeks. This was accompanied by early-onset severe portal hypertension and twofold to fourfold increase in profibrogenic transcripts Col1a1 [procollagen ?1(I)], Tgfb1, and Timp1. Primary liver cancers in BALB/c.Mdr2(-/-) developed earlier, with greater tumor burden compared to FVB.Mdr2(-/-). BALB/c.Mdr2(-/-) mice have unprecedented degree and rapidity of hepatic fibrosis progression and clinically relevant cirrhosis complications, such as early-onset portal hypertension and primary liver cancers. This new model will facilitate development of antifibrotic drugs and studies into mechanisms of biliary fibrosis progression. PMID:25478810

  17. Bilingual language processing after a lesion in the left thalamic and temporal regions. A case report with early childhood onset

    SciTech Connect

    van Lieshout, P.; Renier, W.; Eling, P.; de Bot, K.; Slis, I. (Univ. of Nijmegen (Netherland))

    1990-02-01

    This case study concerns an 18-year-old bilingual girl who suffered a radiation lesion in the left (dominant) thalamic and temporal region when she was 4 years old. Language and memory assessment revealed deficits in auditory short-term memory, auditory word comprehension, nonword repetition, syntactic processing, word fluency, and confrontation naming tasks. Both languages (English and Dutch) were found to be affected in a similar manner, despite the fact that one language (English) was acquired before and the other (Dutch) after the period of lesion onset. Most of the deficits appear to be related to verbal (short-term) memory dysfunction. Several hypotheses of subcortical involvement in memory processes are discussed with reference to existing theories in this area.

  18. Single nucleotide polymorphisms associated with aggressive periodontitis and severe chronic periodontitis in Japanese

    Microsoft Academic Search

    Asami Suzuki; Guijin Ji; Yukihiro Numabe; Masaaki Muramatsu; Kazuhiro Gomi; Mikimoto Kanazashi; Yorimasa Ogata; Emi Shimizu; Yoshihiro Shibukawa; Akiyo Ito; Taichi Ito; Akira Sugaya; Takashi Arai; Satoru Yamada; Shinji Deguchi; Kyuichi Kamoi

    2004-01-01

    Periodontitis is a common inflammatory disease causing destruction of periodontal tissues. It is a multifactor disease involving genetic factors and oral environmental factors. To determine genetic risk factors associated with aggressive periodontitis or severe chronic periodontitis, single nucleotide polymorphisms (SNPs) in multiple candidate genes were investigated in Japanese. We studied 134 patients with aggressive periodontitis, 117 patients with severe chronic

  19. Mol Psychiatry . Author manuscript A SNAP25 promoter variant is associated with early-onset bipolar disorder

    E-print Network

    Boyer, Edmond

    Mol Psychiatry . Author manuscript Page /1 8 A SNAP25 promoter variant is associated with early , Universit Paris XII Val de Marneé , IFR10 , FR P le de psychiatrie2 ô AP-HP , Groupe Henri Mondor-Albert Chenevier , Cr teil,FRé Service de psychiatrie et psychologie clinique3 CHU Nancy , H pital Jeanne-d Arcô

  20. Lymph Node Flow Cytometry as a Prompt Recognition of Ultra Early Onset PTLD: A Successful Case of Rituximab Treatment

    PubMed Central

    Li, Xiaofan; Li, Nainong; Yang, Ting; Chen, Zhizhe; Hu, Jianda

    2015-01-01

    Ultra early posttransplantation lymphoproliferative disorder (PTLD) is a rare and fatal complication after hematopoietic stem cell transplantation (HSCT). Here we report, by lymph node (LN) flowcytometry, that we early recognized ultra early PTLD after an HLA-matched sibling allo-HSCT followed by a successful treatment with anti-CD20 antibody (rituximab) in a patient in progress disease for angioimmunoblastic T-cell lymphoma (AITL). The patient was conditioned with a reduced intensity conditioning (RIC) regimen. One week after transplantation, the patient developed high fever, generalized fatigue, high Epstein-Barr virus (EBV) load, and LN enlargement. An LN lymphocyte suspension and peripheral blood flowcytometry was performed to find majority of LN lymphocytes highly expressed CD20. By highly suspicious PTLD, 4 doses of rituximab (375?mg/m2?qw) were given immediately followed by reducing and withdrawing immunosuppressant reagent. PTLD was later confirmed by pathology. The patient had good response to rituximab, showing absence of fever, reduction in LN size, and no detectable EBV-DNA. Twenty months after HSCT, the patient remains well without evidence of AITL and PTLD. The current report is one of the earliest cases of PTLD after HSCT. Taken together, by LN flowcytometry as a prompt recognition, rituximab can be an effective preemptive therapy for ultra early developed PTLD. PMID:25878909

  1. Early Onset of Regional Intestinal Ischemia Can Be Detected with Carbon Dioxide Tension Measurement Inside the Peritoneal Cavity

    Microsoft Academic Search

    Gisbert Knichwitz; Paul Reinhold; Frank Schaumann; Klaus Dieter Richter; Hugo Van Aken

    2000-01-01

    Methods for detecting regional gastrointestinal ischemia are rare. An early detection of ischemia in the stomach or ileum can be achieved by the continuous intramucosal Pco2 (Pico2) measurement in the region. However, phys- iological consideration suggests that the placement of a fiberoptic CO2 sensor in the peritoneal cavity should yield comparable results. We tested the hypothesis that a con- tinuous

  2. Early-onset posterior reversible encephalopathy syndrome after solid organ transplantation in pediatric patients: a report of 2 cases.

    PubMed

    Araz, C; Camkiran, A; Zeyneloglu, P; Sezgin, A; Moray, G; Pirat, A; Arslan, G

    2013-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a neurological disturbance that occurs due to different reasons and presents with different clinical symptoms. It can be a devastating situation, but, timely treatment may lead to complete recovery. We report 2 cases of PRES, which developed and fully recovered in the early period after solid organ transplantation in pediatric patients. PMID:24314957

  3. Early metabolic changes following ischemia onset in rats: An in vivo diffusion-weighted imaging and 1H-magnetic resonance spectroscopy study at 7.0 T

    PubMed Central

    YAN, GEN; DAI, ZHUOZHI; XUAN, YINGHUA; WU, RENHUA

    2015-01-01

    Despite improvements in imaging techniques, it remains challenging to quantitatively assess the time of ischemic onset of an acute ischemic stroke. It is crucial to evaluate the early signs of infarction, which are predictive of responses to recombinant tissue plasminogen activator within a treatment window of 4.5 h after stroke induction. The aim of the present study was to assess and quantify the onset time for hyperacute middle cerebral artery occlusion (MCAO) ischemic stroke by measuring the apparent diffusion coefficient (ADC) of diffusion-weighted imaging (DWI) and 1H-magnetic resonance spectroscopy (MRS) at 7.0 T. DWI, conventional T2-weighted imaging (T2WI) and subsequent focal ADCs were employed to evaluate ischemic brain lesions in a rat model of MCAO (n=20) at different time-points following a stroke. A quantitation of local changes in metabolite concentrations within the lesions was performed using MRS. Proton metabolites were quantified automatically using LCModel software. At 30 min after MCAO, intense signals were observed in the DWI spectra of all animals. No abnormal signal was observed within 3 h by T2WI. ADC images of the central area, peripheral striping and on the fringes of the infarction demonstrated a lower signal than that of the normal side. The ADC decreased significantly within 30 min after infarction, followed by a gradual elevation in volatility levels and then becoming relatively stable at a lower level 3 h later. MRS exhibited a consistent elevation of lactate and reduced N-acetyl aspartic acid. Glutamate and taurine reached a maximum 2 h after MCAO and began to decrease 1 h later. In conclusion, the present study demonstrated that hyperacute ischemic stroke can be quantitatively detected with the application of ADC, DWI and MRS. These methods may also be used to quantitatively assess the ischemic onset time of a hyperacute stroke. PMID:25634261

  4. Intestinal mucosal adherence and translocation of commensal bacteria at the early onset of type 2 diabetes: molecular mechanisms and probiotic treatment

    PubMed Central

    Amar, Jacques; Chabo, Chantal; Waget, Aurélie; Klopp, Pascale; Vachoux, Christelle; Bermúdez-Humarán, Luis G; Smirnova, Natalia; Bergé, Mathieu; Sulpice, Thierry; Lahtinen, Sampo; Ouwehand, Arthur; Langella, Philippe; Rautonen, Nina; Sansonetti, Philippe J; Burcelin, Rémy

    2011-01-01

    A fat-enriched diet modifies intestinal microbiota and initiates a low-grade inflammation, insulin resistance and type-2 diabetes. Here, we demonstrate that before the onset of diabetes, after only one week of a high-fat diet (HFD), live commensal intestinal bacteria are present in large numbers in the adipose tissue and the blood where they can induce inflammation. This translocation is prevented in mice lacking the microbial pattern recognition receptors Nod1 or CD14, but overtly increased in Myd88 knockout and ob/ob mouse. This ‘metabolic bacteremia’ is characterized by an increased co-localization with dendritic cells from the intestinal lamina propria and by an augmented intestinal mucosal adherence of non-pathogenic Escherichia coli. The bacterial translocation process from intestine towards tissue can be reversed by six weeks of treatment with the probiotic strain Bifidobacterium animalis subsp. lactis 420, which improves the animals' overall inflammatory and metabolic status. Altogether, these data demonstrate that the early onset of HFD-induced hyperglycemia is characterized by an increased bacterial translocation from intestine towards tissues, fuelling a continuous metabolic bacteremia, which could represent new therapeutic targets. PMID:21735552

  5. Perilous periodontitis: a clinical study.

    PubMed

    Emmanuel, Roby V; Neelakantan, Shiba

    2011-12-01

    The aim of this study is to determine whether periodontitis in pregnant women could be a risk factor for pre term low birth weight. The oral hygiene status, periodontal status and periodontal treatment needs of mothers who birthed infants with normal birth weight and normal gestation period (group A) and mothers who birthed pre term low birth weight infants (group B) were assessed and compared. The clinical parameters used were Oral Hygiene Index--simplified (OHI-S), gingival bleeding index (GBI), probing pocket depth and Community Periodontal Index of Treatment Needs (CPITN). This article presents the study and its findings and draws conclusions as to the relationship between poor periodontal condition and pre term low birth weight. PMID:22216586

  6. Early onset Charcot-Marie-Tooth type 1B disease caused by a novel Leu190fs mutation in the myelin protein zero gene.

    PubMed

    Kocha?ski, Andrzej; Kabzi?ska, Dagmara; Drac, Hanna; Ryniewicz, Barbara; Rowi?ska-Marci?ska, Katarzyna; Hausmanowa-Petrusewicz, Irena

    2004-01-01

    The spectrum of Charcot-Marie-Tooth (CMT) phenotypes segregating with mutations in the Myelin Protein Zero (MPZ) gene is wide and ranges from congenital hypomyelinating neuropathy (CHN) through demyelinating form of CMT to the axonal type of CMT disease. Within 94 MPZ gene mutations reported up to now, only a few were identified in the exon 4 of the MPZ gene. In this study we have identified a novel Leu190fs mutation in the MPZ gene. The Leu190fs mutation was found in a 14-year-old girl suffering from Charcot-Marie-Tooth type 1 disease (CMT1) with onset in early infancy. Similarly to the other MPZ gene frame-shift mutations reported as far the Leu190fs seems to have a dominant negative effect. PMID:15261887

  7. Homozygous NOTCH3 null mutation and impaired NOTCH3 signaling in recessive early-onset arteriopathy and cavitating leukoencephalopathy

    PubMed Central

    Pippucci, Tommaso; Maresca, Alessandra; Magini, Pamela; Cenacchi, Giovanna; Donadio, Vincenzo; Palombo, Flavia; Papa, Valentina; Incensi, Alex; Gasparre, Giuseppe; Valentino, Maria Lucia; Preziuso, Carmela; Pisano, Annalinda; Ragno, Michele; Liguori, Rocco; Giordano, Carla; Tonon, Caterina; Lodi, Raffaele; Parmeggiani, Antonia; Carelli, Valerio; Seri, Marco

    2015-01-01

    Notch signaling is essential for vascular physiology. Neomorphic heterozygous mutations in NOTCH3, one of the four human NOTCH receptors, cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Hypomorphic heterozygous alleles have been occasionally described in association with a spectrum of cerebrovascular phenotypes overlapping CADASIL, but their pathogenic potential is unclear. We describe a patient with childhood-onset arteriopathy, cavitating leukoencephalopathy with cerebral white matter abnormalities presented as diffuse cavitations, multiple lacunar infarctions and disseminated microbleeds. We identified a novel homozygous c.C2898A (p.C966*) null mutation in NOTCH3 abolishing NOTCH3 expression and causing NOTCH3 signaling impairment. NOTCH3 targets acting in the regulation of arterial tone (KCNA5) or expressed in the vasculature (CDH6) were downregulated. Patient's vessels were characterized by smooth muscle degeneration as in CADASIL, but without deposition of granular osmiophilic material (GOM), the CADASIL hallmark. The heterozygous parents displayed similar but less dramatic trends in decrease in the expression of NOTCH3 and its targets, as well as in vessel degeneration. This study suggests a functional link between NOTCH3 deficiency and pathogenesis of vascular leukoencephalopathies. PMID:25870235

  8. Mutational analysis of BRCA1 and BRCA2 in Mediterranean Spanish women with early-onset breast cancer: identification of three novel pathogenic mutations.

    PubMed

    Martínez-Ferrandis, J I; Vega, A; Chirivella, I; Marín-García, P; Insa, A; Lluch, A; Carracedo, A; Chaves, F J; García-Conde, J; Cervantes, A; Armengod, M-E

    2003-11-01

    In Spain, the contribution of BRCA mutations to the population incidence of early-onset breast cancer was unknown. We carried out a mutational analysis of the BRCA1 and BRCA2 genes in 124 Spanish women diagnosed with breast cancer before the age 41 and who were not selected for a family history of this disease. The genetic study was performed by PCR-SSCP analysis and DNA sequencing. We identified 6 pathogenic BRCA mutations in 7 unrelated probands (5.6%; 95% CI=2.3% to 11.3%): 1 BRCA1 (c.2080delA) and 5 BRCA2 (p.Y3006X, p.Q1994X, c.9204_9217del14, c.9254_9258del5 and c.295+2T>C). Three out of 6 mutations were novel (BRCA2 p.Y3006X, c.9204_9217del14, and c.295+2T>C), and two further mutations had not been previously found in Spain (BRCA1 c.2080delA and BRCA2 p.Q1994X). The one remaining (BRCA2 c.9254_9258del5) was detected in two probands of our sample. Additionally, we identified two new missense mutations: BRCA1 p.P1812A and BRCA2 p.G2044A. Our data support the notion that Spaniards represent a heterogeneous population with its own spectrum of BRCA mutations, some of which appear as founding mutations. We categorized patients into familial or non-familial groups on the basis of her family history of breast/ovarian cancer; this analysis indicated that among Spanish women with early-onset breast cancer, an even moderate family history is a good predictor of being a BRCA mutation carrier. PMID:14517958

  9. Cost-effectiveness analysis of intravenous levetiracetam versus intravenous phenytoin for early onset seizure prophylaxis after neurosurgery and traumatic brain injury

    PubMed Central

    Kazerooni, Rashid; Bounthavong, Mark

    2010-01-01

    Objective: There has been growing interest in newer anti-epileptic drugs (AEDs) for seizure prophylaxis in the intensive care setting because of safety and monitoring issues associated with conventional AEDs like phenytoin. This analysis assessed the cost-effectiveness of levetiracetam versus phenytoin for early onset seizure prophylaxis after neurosurgery and traumatic brain injury (TBI). Methods: A cost-effectiveness analysis was conducted from the US hospital perspective using a decision analysis model. Probabilities of the model were taken from three studies comparing levetiracetam and phenytoin in post neurosurgery or TBI patients. The outcome measure was successful seizure prophylaxis regimen (SSPR) within 7 days, which was defined as patients who did not seize or require discontinuation of the AED due to adverse drug reactions (ADRs). One-way sensitivity analyses and probabilistic sensitivity analysis were conducted to test robustness of the base-case results. Results: The total direct costs for seizure prophylaxis were $8,784.63 and $8,743.78 for levetiracetam and phenytoin, respectively. The cost-effectiveness ratio of levetiracetam was $10,044.91 per SSPR compared to $11,525.63 per SSPR with phenytoin. The effectiveness probability (patients with no seizures and no ADR requiring change in therapy) was higher in the levetiracetam group (87.5%) versus the phenytoin group (75.9%). The incremental cost effectiveness ratio for levetiracetam versus phenytoin was $360.82 per additional SSPR gained. Conclusions: Levetiracetam has the potential to be more cost-effective than phenytoin for early onset seizure prophylaxis after neurosurgery if the payer’s willingness-to-pay is greater than $360.82 per additional SSPR gained. PMID:21935311

  10. Association of early-onset dementia with activities of daily living (ADL) in middle-aged adults with intellectual disabilities: the caregiver's perspective.

    PubMed

    Lin, Lan-Ping; Hsu, Shang-Wei; Hsia, Yi-Chen; Wu, Chia-Ling; Chu, Cordia; Lin, Jin-Ding

    2014-03-01

    Few studies have investigated in detail which factors influence activities of daily living (ADL) in adults with intellectual disabilities (ID) comorbid with/without dementia conditions. The objective of the present study was to describe the relation between early onset dementia conditions and progressive loss of ADL capabilities and to examine the influence of dementia conditions and other possible factors toward ADL scores in adults with ID. This study was part of the "Healthy Aging Initiatives for Persons with an Intellectual Disability in Taiwan: A Social Ecological Approach" project. We analyzed data from 459 adults aged 45 years or older with an ID regarding their early onset symptoms of dementia and their ADL profile based on the perspective of the primary caregivers. Results show that a significant negative correlation was found between dementia score and ADL score in a Pearson's correlation test (r=-0.28, p<0.001). The multiple linear regression model reported that factors of male gender (?=4.187, p<0.05), marital status (?=4.79, p<0.05), education level (primary: ?=5.544, p<0.05; junior high or more: ?=8.147, p<0.01), Down's syndrome (?=-9.290, p<0.05), severe or profound disability level (?=-6.725, p<0.05; ?=-15.773, p<0.001), comorbid condition (?=-4.853, p<0.05) and dementia conditions (?=-9.245, p<0.001) were variables that were able to significantly predict the ADL score (R(2)=0.241) after controlling for age. Disability level and comorbidity can explain 10% of the ADL score variation, whereas dementia conditions can only explain 3% of the ADL score variation in the study. The present study highlights that future studies should scrutinize in detail the reasons for the low explanatory power of dementia for ADL, particularly in examining the appropriateness of the measurement scales for dementia and ADL in aging adults with ID. PMID:24467810

  11. Comprehensive analysis of BRCA1, BRCA2 and TP53 germline mutation and tumor characterization: a portrait of early-onset breast cancer in Brazil.

    PubMed

    Carraro, Dirce Maria; Koike Folgueira, Maria Aparecida Azevedo; Garcia Lisboa, Bianca Cristina; Ribeiro Olivieri, Eloisa Helena; Vitorino Krepischi, Ana Cristina; de Carvalho, Alex Fiorini; de Carvalho Mota, Louise Danielle; Puga, Renato David; do Socorro Maciel, Maria; Michelli, Rodrigo Augusto Depieri; de Lyra, Eduardo Carneiro; Grosso, Stana Helena Giorgi; Soares, Fernando Augusto; Achatz, Maria Isabel Alves de Souza Waddington; Brentani, Helena; Moreira-Filho, Carlos Alberto; Brentani, Maria Mitzi

    2013-01-01

    Germline mutations in BRCA1, BRCA2 and TP53 genes have been identified as one of the most important disease-causing issues in young breast cancer patients worldwide. The specific defective biological processes that trigger germline mutation-associated and -negative tumors remain unclear. To delineate an initial portrait of Brazilian early-onset breast cancer, we performed an investigation combining both germline and tumor analysis. Germline screening of the BRCA1, BRCA2, CHEK2 (c.1100delC) and TP53 genes was performed in 54 unrelated patients <35 y; their tumors were investigated with respect to transcriptional and genomic profiles as well as hormonal receptors and HER2 expression/amplification. Germline mutations were detected in 12 out of 54 patients (22%) [7 in BRCA1 (13%), 4 in BRCA2 (7%) and one in TP53 (2%) gene]. A cancer familial history was present in 31.4% of the unrelated patients, from them 43.7% were carriers for germline mutation (37.5% in BRCA1 and in 6.2% in the BRCA2 genes). Fifty percent of the unrelated patients with hormone receptor-negative tumors carried BRCA1 mutations, percentage increasing to 83% in cases with familial history of cancer. Over-representation of DNA damage-, cellular and cell cycle-related processes was detected in the up-regulated genes of BRCA1/2-associated tumors, whereas cell and embryo development-related processes were over-represented in the up-regulated genes of BRCA1/2-negative tumors, suggesting distinct mechanisms driving the tumorigenesis. An initial portrait of the early-onset breast cancer patients in Brazil was generated pointing out that hormone receptor-negative tumors and positive familial history are two major risk factors for detection of a BRCA1 germline mutation. Additionally, the data revealed molecular factors that potentially trigger the tumor development in young patients. PMID:23469205

  12. Early onset of Chanarin-Dorfman syndrome with severe liver involvement in a patient with a complex rearrangement of ABHD5 promoter

    PubMed Central

    2014-01-01

    Background ?/?-hydrolase domain-containing protein 5 (ABHD5) plays an important role in the triacylglycerols (TAG) hydrolysis. Indeed, ABHD5 is the co-activator of adipose triglyceride lipase (ATGL), that catalyses the initial step of TAG hydrolysis. Mutations in ABHD5 gene are associated with the onset of Chanarin-Dorfman syndrome (CDS), a rare autosomal recessive lipid storage disorder, characterized by non-bullous congenital ichthyosiform erythroderma (NCIE), hepatomegaly and liver steatosis. Case presentation We describe here a 5-years-old Brazilian child who presented with NCIE at birth and diffuse micro and macro-vesicular steatosis on liver biopsy since she was 2 years old. Molecular analysis of coding sequence and putative 5? regulatory region of ABHD5 gene was performed. A homozygous novel deletion, affecting the promoter region and the exon 1, was identified, confirming the suspected diagnosis of CDS for this patient. RT-PCR analysis showed that the genomic rearrangement completely abolished the ABHD5 gene expression in the patient, while only a partial loss of expression was detected in her parents. This is the first report describing the identification of a large deletion encompassing the promoter region of ABHD5 gene. The total loss of ABHD5 expression may explain the early onset of CDS and the severe liver involvement. After molecular diagnosis, the patient started a special diet, poor in fatty acids with medium chain triglycerides (MCT), and showed hepatic and dermatologic improvement in spite of severe molecular defect. Conclusions This case report extends the spectrum of disease-causing ABHD5 mutations in CDS providing evidence for a novel pathogenic mechanism for this rare disorder. Moreover, our preliminary data show that early diagnosis and prompt treatment of neutral lipid accumulation might be useful for CD patients. PMID:24628803

  13. TREM-1 Expression Is Increased in Human Placentas From Severe Early-Onset Preeclamptic Pregnancies Where It May Be Involved in Syncytialization

    PubMed Central

    Lim, Ratana; Barker, Gillian

    2014-01-01

    Preeclampsia, a major cause of maternal and perinatal morbidity and mortality, is thought to be attributable to dysregulation of trophoblast invasion and differentiation. Microarray studies have shown that triggering receptor expressed on myeloid cells (TREM) 1, a cell surface molecule involved in the inflammatory response, is increased in preeclamptic placentas. The aim of this study was to determine the level of TREM-1 expression in severe early-onset preeclamptic placentas and its functional role in trophoblast differentiation. Placenta was obtained from women with severe early-onset preeclampsia (n = 19) and gestationally matched preterm controls placentas (n = 8). The TREM-1 expression was determined by quantitative reverse transcriptase polymerase chain reaction and Western blotting. The effect of TREM-1 small interfering RNA on cell fusion and differentiation was assessed in BeWo cells. The effect of oxygen tension on TREM-1 levels, in basal or forskolin-treated BeWo cells, was also assessed. The TREM-1 was localized to the syncytiotrophoblast layer, and TREM-1 messenger RNA and protein expression was significantly increased in preeclamptic placentas. The BeWo cells treated with forskolin were associated with increased TREM-1 expression. The TREM-1 knockdown inhibited forskolin-induced expression of the differentiation marker ?-human chorionic gonadotropin but had no effect on the cell-fusion marker E-cadherin. The increase in TREM-1 expression in BeWo cells treated with forskolin during normoxic conditions was reduced in forskolin-treated cells under hypoxic conditions. In conclusion, TREM-1 is increased in preeclamptic placentas and by forskolin treatment. Knockdown of TREM-1 by RNA interference inhibits cell differentiation but has no effect on cell–cell fusion. Finally, we show that TREM-1 upregulation is attenuated under hypoxic conditions in which cell differentiation is impaired. PMID:24026310

  14. TREM-1 expression is increased in human placentas from severe early-onset preeclamptic pregnancies where it may be involved in syncytialization.

    PubMed

    Lim, Ratana; Barker, Gillian; Lappas, Martha

    2014-05-01

    Preeclampsia, a major cause of maternal and perinatal morbidity and mortality, is thought to be attributable to dysregulation of trophoblast invasion and differentiation. Microarray studies have shown that triggering receptor expressed on myeloid cells (TREM) 1, a cell surface molecule involved in the inflammatory response, is increased in preeclamptic placentas. The aim of this study was to determine the level of TREM-1 expression in severe early-onset preeclamptic placentas and its functional role in trophoblast differentiation. Placenta was obtained from women with severe early-onset preeclampsia (n = 19) and gestationally matched preterm controls placentas (n = 8). The TREM-1 expression was determined by quantitative reverse transcriptase polymerase chain reaction and Western blotting. The effect of TREM-1 small interfering RNA on cell fusion and differentiation was assessed in BeWo cells. The effect of oxygen tension on TREM-1 levels, in basal or forskolin-treated BeWo cells, was also assessed. The TREM-1 was localized to the syncytiotrophoblast layer, and TREM-1 messenger RNA and protein expression was significantly increased in preeclamptic placentas. The BeWo cells treated with forskolin were associated with increased TREM-1 expression. The TREM-1 knockdown inhibited forskolin-induced expression of the differentiation marker ?-human chorionic gonadotropin but had no effect on the cell-fusion marker E-cadherin. The increase in TREM-1 expression in BeWo cells treated with forskolin during normoxic conditions was reduced in forskolin-treated cells under hypoxic conditions. In conclusion, TREM-1 is increased in preeclamptic placentas and by forskolin treatment. Knockdown of TREM-1 by RNA interference inhibits cell differentiation but has no effect on cell-cell fusion. Finally, we show that TREM-1 upregulation is attenuated under hypoxic conditions in which cell differentiation is impaired. PMID:24026310

  15. Periodontal Disease Status in Gullah African Americans with Type 2 Diabetes living in South Carolina

    PubMed Central

    Fernandes, Jyotika K; Wiegand, Ryan E; Salinas, Carlos F.; Grossi, Sarah G; Sanders, John J; Lopes-Virella, Maria F.; Slate, Elizabeth H.

    2010-01-01

    Background African Americans have a disproportionate burden of diabetes. Gullah African Americans are the most genetically homogeneous population of African descent in the US, with an estimated European Caucasian admixture of only 3.5%. This study assessed the previously unknown prevalence of periodontal disease among a sample of Gullah African Americans with diabetes and investigated the association between diabetes control and presence of periodontal disease. Methods Gullah African Americans with Type 2 diabetes (n=235) were included. Diabetes control was assessed by HbA1C, and divided into three categories: well controlled, <7%; moderately controlled, 7–8.5%; and poorly controlled, >8.5%. Participants were categorized as healthy, having no clinical attachment loss (CAL) or bleeding on probing (BOP); early periodontitis, having CAL ?1 mm in ?2 teeth; moderate periodontitis, having 3 sites with CAL ?4 mm and at least 2 sites with probing depth (PD) ?3 mm; and severe periodontitis, having CAL ?6 mm in ?2 teeth and PD ?5 mm in ?1 site. Observed prevalences of periodontitis were compared to rates reported for the NHANES studies. Results All subjects had evidence of periodontal disease: 70.6% had moderate periodontitis and 28.5% had severe disease. Diabetes control was not associated with periodontal disease. The periodontal disease proportions were significantly higher than the reported national prevalence of 10.6% among African Americans without diabetes. Conclusions Our sample of Gullah African Americans with type 2 diabetes exhibits higher prevalence of periodontal disease than African Americans, both with and without diabetes, described in NHANES III and NHANES 1999–2000. PMID:19563285

  16. Synchrotron radiation analysis of possible correlations between metal status in human cementum and periodontal disease

    SciTech Connect

    Martin, R.R.; Naftel, S.J.; Nelson, A.J.; Edwards, M.; Mithoowani, H.; Stakiw, J. (UWO); (Saskatchewan)

    2010-03-16

    Periodontitis is a serious disease that affects up to 50% of an adult population. It is a chronic condition involving inflammation of the periodontal ligament and associated tissues leading to eventual tooth loss. Some evidence suggests that trace metals, especially zinc and copper, may be involved in the onset and severity of periodontitis. Thus we have used synchrotron X-ray fluorescence imaging on cross sections of diseased and healthy teeth using a microbeam to explore the distribution of trace metals in cementum and adhering plaque. The comparison between diseased and healthy teeth indicates that there are elevated levels of zinc, copper and nickel in diseased teeth as opposed to healthy teeth. This preliminary correlation between elevated levels of trace metals in the cementum and plaque of diseased teeth suggests that metals may play a role in the progress of periodontitis.

  17. Substance Use Progression from Adolescence to Early Adulthood: Effortful Control in the Context of Friendship Influence and Early-Onset Use

    ERIC Educational Resources Information Center

    Piehler, Timothy F.; Veronneau, Marie-Helene; Dishion, Thomas J.

    2012-01-01

    In a sample of 998 ethnically diverse adolescents, a multiagent, multimethod approach to the measurement of adolescent effortful control, adolescent substance use, and friendship influence was used to predict escalations to early-adult tobacco, alcohol, and marijuana use by ages 22-23. Structural equation modeling revealed that adolescent…

  18. Choice of diagnostic and therapeutic imaging in periodontics and implantology

    PubMed Central

    Chakrapani, Swarna; Sirisha, K.; Srilalitha, Anumadi; Srinivas, Moogala

    2013-01-01

    Imaging forms an integral component for diagnosis of dental and in specific periodontal diseases. To date, intra-oral radiographic techniques are the main non-invasive diagnostic aids for the detection and assessment of internal changes in mineralized periodontal tissues like alveolar bone. These analog radiographic techniques suffer from inherent limitations like: Two dimensional projection, magnification, distortion, superimposition and misrepresentation of anatomic structures. The evolution of novel imaging modalities, namely cone beam computed tomography, tuned aperture CT empowered dental researchers to visualize the periodontium three dimensionally. This improves interpretation of structural and biophysical changes, ensures densitometric assessments of dentoalveolar structures including variations in alveolar bone density, and peri-implant bone healing more precisely. This detailed review, highlights current leading edge concepts, envisions a wide range of imaging modalities which pave the way for better understanding and early intervention of periodontal diseases. PMID:24554878

  19. Identification of azurocidin as a potential periodontitis biomarker by a proteomic analysis of gingival crevicular fluid

    PubMed Central

    2011-01-01

    Background The inflammatory disease periodontitis results in tooth loss and can even lead to diseases of the whole body if not treated. Gingival crevicular fluid (GCF) reflects the condition of the gingiva and contains proteins transuded from serum or cells at inflamed sites. In this study, we aimed to discover potential protein biomarkers for periodontitis in GCF proteome using LC-MS/MS. Results We identified 305 proteins from GCF of healthy individuals and periodontitis patients collected using a sterile gel loading tip by ESI-MS/MS coupled to nano-LC. Among these proteins, about 45 proteins were differentially expressed in the GCF proteome of moderate periodontitis patients when compared to the healthy individuals. We first identified azurocidin in the GCF, but not the saliva, as an upregulated protein in the periodontitis patients and verified its increased expression during periodontitis by ELISA using the GCF of the classified periodontitis patients compared to the healthy individuals. In addition, we found that azurocidin inhibited the differentiation of bone marrow-derived macrophages to osteoclasts. Conclusions Our results show that GCF collection using a gel loading tip and subsequent LC-MS/MS analysis following 1D-PAGE proteomic separation are effective for the analysis of the GCF proteome. Our current results also suggest that azurocidin could be a potential biomarker candidate for the early detection of inflammatory periodontal destruction by gingivitis and some chronic periodontitis. Our data also suggest that azurocidin may have an inhibitory role in osteoclast differentiation and, thus, a protective role in alveolar bone loss during the early stages of periodontitis. PMID:21794177

  20. Clinical improvement and radiological progression in a girl with early onset scoliosis (EOS) treated conservatively – a case report

    PubMed Central

    Weiss, Hans-Rudolf

    2006-01-01

    Background Chêneau-Brace treatment of a certain standard reduces the rate of surgery, prevents progression and in a certain patient population leads to marked improvement of Cobb angle and cosmetic appearance. During the last two years a patient refusing surgery with a double major curvature of initially 60° showed a clear cosmetic improvement and a clear radiological progression at the same time. The findings of this patient have been reviewed in order to find out how cosmetic appearance and Cobb angle can develop differently. Methods The patient entered conservative treatment at the age of 13 years, premenarchial with Tanner II and a Cobb angle of 60° thoracic and 59° lumbar. The angle of trunk rotation (ATR; Scoliometer) was 13° thoracic and 13° lumbar. We have documented the findings of this patient (Surface topography, ATR, Cobb angles and angles of vertebral rotation (according to Raimondi) during the treatment period (27 Month) until 2 years after the onset of menarche. Results After a treatment time of 27 Month the Cobb angle increased to 74° thoracic and 65° lumbar. The angles of vertebral rotation according to Raimondi increased slightly from 26° thoracic and 28° lumbar to 30° thoracic and 28° lumbar. The ATR improved to 12° thoracic and 5° lumbar while Lateral deviation improved from 22,4 mm to 4,6 mm and average surface rotation improved from 10,6° to 6°. In the X-rays a reduction of decompensation was visible. The patient felt comfortable with the cosmetic result. Conclusion Conservative treatment may improve cosmetic appearance while the curve progresses radiologically. This could be explained by assuming that (1) the Rigo Chêneau brace is able to improve cosmetic appearance by changing the shape of the thorax when the curve itself is too stiff to be corrected by a brace, that (2) reduction of decompensation leads to significant cosmetical improvements or (3) that the patient gained weight and therefore the deformation is masked. However, the weight the patient gained cannot explain the cosmetical improvement in this case. Conservative treatment with a certain standard of quality seems a viable alternative for patients with Cobb angles of > 60° when surgical treatment is refused. Specialists in scoliosis management should be aware of the fact that curve progression can occur even if the clinical measurements show an improvement. PMID:16872503

  1. The Eocene climate of China, the early elevation of the Tibetan Plateau and the onset of the Asian Monsoon.

    PubMed

    Wang, Qing; Spicer, Robert A; Yang, Jian; Wang, Yu-Fei; Li, Cheng-Sen

    2013-12-01

    Eocene palynological samples from 37 widely distributed sites across China were analysed using co-existence approach to determine trends in space and time for seven palaeoclimate variables: Mean annual temperature, mean annual precipitation, mean temperature of the warmest month, mean temperature of the coldest month, mean annual range of temperature, mean maximum monthly precipitation and mean minimum monthly precipitation. Present day distributions and observed climates within China of the nearest living relatives of the fossil forms were used to find the range of a given variable in which a maximum number of taxa can coexist. Isotherm and isohyet maps for the early, middle and late Eocene were constructed. These illustrate regional changing patterns in thermal and precipitational gradients that may be interpreted as the beginnings of the modern Asian Monsoon system, and suggest that the uplift of parts of the Tibetan Plateau appear to have taken place by the middle to late Eocene. PMID:23893567

  2. A carapace-like bony 'body tube' in an early triassic marine reptile and the onset of marine tetrapod predation.

    PubMed

    Chen, Xiao-hong; Motani, Ryosuke; Cheng, Long; Jiang, Da-yong; Rieppel, Olivier

    2014-01-01

    Parahupehsuchus longus is a new species of marine reptile from the Lower Triassic of Yuan'an County, Hubei Province, China. It is unique among vertebrates for having a body wall that is completely surrounded by a bony tube, about 50 cm long and 6.5 cm deep, comprising overlapping ribs and gastralia. This tube and bony ossicles on the back are best interpreted as anti-predatory features, suggesting that there was predation pressure upon marine tetrapods in the Early Triassic. There is at least one sauropterygian that is sufficiently large to feed on Parahupehsuchus in the Nanzhang-Yuan'an fauna, together with six more species of potential prey marine reptiles with various degrees of body protection. Modern predators of marine tetrapods belong to the highest trophic levels in the marine ecosystem but such predators did not always exist through geologic time. The indication of marine-tetrapod feeding in the Nanzhang-Yuan'an fauna suggests that such a trophic level emerged for the first time in the Early Triassic. The recovery from the end-Permian extinction probably proceeded faster than traditionally thought for marine predators. Parahupehsuchus has superficially turtle-like features, namely expanded ribs without intercostal space, very short transverse processes, and a dorsal outgrowth from the neural spine. However, these features are structurally different from their turtle counterparts. Phylogeny suggests that they are convergent with the condition in turtles, which has a fundamentally different body plan that involves the folding of the body wall. Expanded ribs without intercostal space evolved at least twice and probably even more among reptiles. PMID:24718682

  3. A Carapace-Like Bony ‘Body Tube’ in an Early Triassic Marine Reptile and the Onset of Marine Tetrapod Predation

    PubMed Central

    Chen, Xiao-hong; Motani, Ryosuke; Cheng, Long; Jiang, Da-yong; Rieppel, Olivier

    2014-01-01

    Parahupehsuchus longus is a new species of marine reptile from the Lower Triassic of Yuan’an County, Hubei Province, China. It is unique among vertebrates for having a body wall that is completely surrounded by a bony tube, about 50 cm long and 6.5 cm deep, comprising overlapping ribs and gastralia. This tube and bony ossicles on the back are best interpreted as anti-predatory features, suggesting that there was predation pressure upon marine tetrapods in the Early Triassic. There is at least one sauropterygian that is sufficiently large to feed on Parahupehsuchus in the Nanzhang-Yuan’an fauna, together with six more species of potential prey marine reptiles with various degrees of body protection. Modern predators of marine tetrapods belong to the highest trophic levels in the marine ecosystem but such predators did not always exist through geologic time. The indication of marine-tetrapod feeding in the Nanzhang-Yuan’an fauna suggests that such a trophic level emerged for the first time in the Early Triassic. The recovery from the end-Permian extinction probably proceeded faster than traditionally thought for marine predators. Parahupehsuchus has superficially turtle-like features, namely expanded ribs without intercostal space, very short transverse processes, and a dorsal outgrowth from the neural spine. However, these features are structurally different from their turtle counterparts. Phylogeny suggests that they are convergent with the condition in turtles, which has a fundamentally different body plan that involves the folding of the body wall. Expanded ribs without intercostal space evolved at least twice and probably even more among reptiles. PMID:24718682

  4. Relationship between diabetes and periodontal infection

    PubMed Central

    Llambés, Fernando; Arias-Herrera, Santiago; Caffesse, Raúl

    2015-01-01

    Periodontal disease is a high prevalent disease. In the United States 47.2% of adults ? 30 years old have been diagnosed with some type of periodontitis. Longitudinal studies have demonstrated a two-way relationship between diabetes and periodontitis, with more severe periodontal tissue destruction in diabetic patients and poorer glycemic control in diabetic subjects with periodontal disease. Periodontal treatment can be successful in diabetic patients. Short term effects of periodontal treatment are similar in diabetic patients and healthy population but, more recurrence of periodontal disease can be expected in no well controlled diabetic individuals. However, effects of periodontitis and its treatment on diabetes metabolic control are not clearly defined and results of the studies remain controversial. PMID:26185600

  5. MpzR98C arrests Schwann cell development in a mouse model of early-onset Charcot–Marie–Tooth disease type 1B

    PubMed Central

    Saporta, Mario A. C.; Shy, Brian R.; Patzko, Agnes; Bai, Yunhong; Pennuto, Maria; Ferri, Cinzia; Tinelli, Elisa; Saveri, Paola; Kirschner, Dan; Crowther, Michelle; Southwood, Cherie; Wu, Xingyao; Gow, Alexander; Feltri, M. Laura; Wrabetz, Lawrence

    2012-01-01

    Mutations in myelin protein zero (MPZ) cause Charcot–Marie–Tooth disease type 1B. Many dominant MPZ mutations, including R98C, present as infantile onset dysmyelinating neuropathies. We have generated an R98C ‘knock-in’ mouse model of Charcot–Marie–Tooth type 1B, where a mutation encoding R98C was targeted to the mouse Mpz gene. Both heterozygous (R98C/+) and homozygous (R98C/R98C) mice develop weakness, abnormal nerve conduction velocities and morphologically abnormal myelin; R98C/R98C mice are more severely affected. MpzR98C is retained in the endoplasmic reticulum of Schwann cells and provokes a transitory, canonical unfolded protein response. Ablation of Chop, a mediator of the protein kinase RNA-like endoplasmic reticulum kinase unfolded protein response pathway restores compound muscle action potential amplitudes of R98C/+ mice but does not alter the reduced conduction velocities, reduced axonal diameters or clinical behaviour of these animals. R98C/R98C Schwann cells are developmentally arrested in the promyelinating stage, whereas development is delayed in R98C/+ mice. The proportion of cells expressing c-Jun, an inhibitor of myelination, is elevated in mutant nerves, whereas the proportion of cells expressing the promyelinating transcription factor Krox-20 is decreased, particularly in R98C/R98C mice. Our results provide a potential link between the accumulation of MpzR98C in the endoplasmic reticulum and a developmental delay in myelination. These mice provide a model by which we can begin to understand the early onset dysmyelination seen in patients with R98C and similar mutations. PMID:22689911

  6. Early Pleistocene onset of Trough-Mouth Fan (TMF) growth on the NW Barents Sea margin: new results based on seismic reflection data

    NASA Astrophysics Data System (ADS)

    Rebesco, Michele; Sverre Laberg, Jan; Pedrosa Gonzalez, Maria Teresa; Camerlenghi, Angelo; Giulia Lucchi, Renata

    2013-04-01

    Among the seismic reflection data acquired within the IPY NICE-STREAM activity (the Spanish SVAIS cruise on board BIO Hespérides in summer 2007 and the Italian EGLACOM cruise on board R/V OGS-Explora in summer 2008), a series of multi-channel profiles provides a nearly 400 km long continuous tie between Ocean Drilling Program Site 986 (offshore Svalbard) and the Kveithola Trough deposits (on the continental shelf just NW of the Bear Island). This tie crosses in strike direction (subparallel to the shelf edge) three TMFs: Bellsund, Hornsund and Storfjorden. Beyond their tie function, these profiles allow us to analyze the characteristics of these TMFs. The seismic units below reflector R4A are relatively uniform in thickness all along the profile, notwithstanding a general northward thinning trend. Conversely, thickening within TMFs is evident essentially only above this reflector. This suggests that for these TMFs the growth appears to have started after the formation of reflection R4A. Thus, the reflection (with an estimated age of about 1.3 Ma) lies in a stratigraphic interval that is recognized as pivotal for the glaciation of the area and the development of the margin. We suggest that it is the reflector that best correspond to the onset of the TMF growth and hence to the onset of the most significant phase of glacial development of the western Barents Sea continental margin. This inference is consistent with a recent finding that contourites produced by deposition of sediments suspended within alongslope bottom currents on the same margin start to develop in correspondence with the same reflector. The availability of suspended sediments for these contourites since Early Pleistocene is ascribed to originate from frequent episodes of small-scale mass-wasting events produced during TMS growth and resulting in more favourable depositional conditions for the Isfjorden and Bellsund contourite drifts.

  7. Loss of serum IGF-I input to the brain as an early biomarker of disease onset in Alzheimer mice

    PubMed Central

    Trueba-Sáiz, A; Cavada, C; Fernandez, A M; Leon, T; González, D A; Fortea Ormaechea, J; Lleó, A; Del Ser, T; Nuñez, A; Torres-Aleman, I

    2013-01-01

    Circulating insulin-like growth factor I (IGF-I) enters the brain and promotes clearance of amyloid peptides known to accumulate in Alzheimer's disease (AD) brains. Both patients and mouse models of AD show decreased level of circulating IGF-I enter the brain as evidenced by a lower ratio of cerebrospinal fluid/plasma IGF-I. Importantly, in presymptomatic AD mice this reduction is already manifested as a decreased brain input of serum IGF-I in response to environmental enrichment. To explore a potential diagnostic use of this early loss of IGF-I input, we monitored electrocorticogram (ECG) responses to systemic IGF-I in mice. Whereas control mice showed enhanced ECG activity after IGF-I, presymptomatic AD mice showed blunted ECG responses. Because nonhuman primates showed identically enhanced electroencephalogram (EEG) activity in response to systemic IGF-I, loss of the EEG signature of serum IGF-I may be exploited as a disease biomarker in AD patients. PMID:24301648

  8. Greater organ involution in highly proliferative tissues associated with the early onset and acceleration of ageing in humans.

    PubMed

    Richardson, Richard B; Allan, David S; Le, Yevgeniya

    2014-07-01

    Domination of cell proliferation over cell death is a driving force for carcinogenesis, whereas reduced cell proliferation and increased cell death are characteristic of ageing. We employed published data to estimate representative mean values of cell turnover times for 31 different organs and tissues in adult humans and animals (when data in humans were lacking) as well as functional mass loss for 5 organs, accounting for actual mass loss and tissue conversion to fat, in humans over the adult period, age 25 to 70. We found that greater actual and functional mass loss was significantly associated (P=0.001 and P<0.0001, respectively) with the log of shorter cell turnover times. We propose that this is characteristic of stem cell exhaustion and replicative senescence. In addition, we provide quantitative evidence that, in many organs, involution is evident even in young adults. On the basis of published mass measurements of major organs, by analysis of covariance, we identified examples of significant (P?0.05), accelerated actual or functional mass loss and ageing from early to late adulthood. We hypothesise and quantitatively demonstrate that functional mass loss accelerates with ageing by incorporating the contribution of actual mass loss, tissue conversion to fatty or fibrous tissue, and the presence of apoptotic, necrotic and senescent cells. We propose that mass loss, linked to replicative senescence, is an evolutionary adaptation that effectively limits cancer in young adults, as mass loss is first apparent soon after the end of the growth period, accelerating in the more elderly as biological conditions deviate away from those prevailing in youth, when the selective pressure on pleiotropic genes is greatest. PMID:24685641

  9. Callous-unemotional behavior and early-childhood onset of behavior problems: the role of parental harshness and warmth.

    PubMed

    Waller, Rebecca; Gardner, Frances; Shaw, Daniel S; Dishion, Thomas J; Wilson, Melvin N; Hyde, Luke W

    2015-01-01

    Youth with callous-unemotional (CU) behavior are at risk of developing more severe forms of aggressive and antisocial behavior. Previous cross-sectional studies suggest that associations between parenting and conduct problems are less strong when children or adolescents have high levels of CU behavior, implying lower malleability of behavior compared to low-CU children. The current study extends previous findings by examining the moderating role of CU behavior on associations between parenting and behavior problems in a very young sample, both concurrently and longitudinally, and using a variety of measurement methods. Data were collected from a multi-ethnic, high-risk sample at ages 2 to 4 (N = 364; 49% female). Parent-reported CU behavior was assessed at age 3 using a previously validated measure (Hyde et al., 2013 ). Parental harshness was coded from observations of parent-child interactions and parental warmth was coded from 5-min speech samples. In this large and young sample, CU behavior moderated cross-sectional correlations between parent-reported and observed warmth and child behavior problems. However, in cross-sectional and longitudinal models testing parental harshness, and longitudinal models testing warmth, there was no moderation by CU behavior. The findings are in line with recent literature suggesting parental warmth may be important to child behavior problems at high levels of CU behavior. In general, however, the results of this study contrast with much of the extant literature and suggest that in young children, affective aspects of parenting appear to be related to emerging behavior problems, regardless of the presence of early CU behavior. PMID:24661288

  10. Effects of diet on early stage cortical perception and discrimination of syllables differing in voice-onset time: A longitudinal ERP study in 3 and 6 month old infants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The influence of infant diet on early stage cortical processing of syllables was examined in 239 healthy infants who were breastfed (BF) or fed milk-based formula (MF) or soy formula (SF). Using an oddball paradigm, event-related potentials to consonant-vowel syllables differing in voice-onset time ...

  11. Periodontitis as a Risk Factor of Atherosclerosis

    PubMed Central

    Bartova, Jirina; Sommerova, Pavla; Lyuya-Mi, Yelena; Mysak, Jaroslav; Janatova, Tatjana; Podzimek, Stepan

    2014-01-01

    Over the last two decades, the amount of evidence corroborating an association between dental plaque bacteria and coronary diseases that develop as a result of atherosclerosis has increased. These findings have brought a new aspect to the etiology of the disease. There are several mechanisms by which dental plaque bacteria may initiate or worsen atherosclerotic processes: activation of innate immunity, bacteremia related to dental treatment, and direct involvement of mediators activated by dental plaque and involvement of cytokines and heat shock proteins from dental plaque bacteria. There are common predisposing factors which influence both periodontitis and atherosclerosis. Both diseases can be initiated in early childhood, although the first symptoms may not appear until adulthood. The formation of lipid stripes has been reported in 10-year-old children and the increased prevalence of obesity in children and adolescents is a risk factor contributing to lipid stripes development. Endothelium damage caused by the formation of lipid stripes in early childhood may lead to bacteria penetrating into blood circulation after oral cavity procedures for children as well as for patients with aggressive and chronic periodontitis. PMID:24741613

  12. The role of tobacco use in periodontal diseases: a literature review.

    PubMed

    Burgan, S W

    1997-01-01

    This article surveys early and current research on the relationship between smoking and various aspects of dental health. Results of early studies on the prevalence of periodontal diseases in smokers, which were often contradictory, are discussed briefly, and more recent research on the effects of tobacco on the periodontium is presented. This includes research examining the relationship--between smoking and the various indicators of periodontitis, such as bone and tooth loss. Studies examining the effect of smoking on the outcome of periodontal therapy, and ways in which tobacco may be harmful are also reviewed, as are the effects of smokeless tobacco on the periodontium. It is suggested that a separate category for smoking-associated periodontitis be created. PMID:9515412

  13. Emerging concepts in periodontal therapy.

    PubMed

    Greenwell, Henry; Bissada, Nabil F

    2002-01-01

    Conventional periodontal therapy consists of mechanical scaling and root planing, and surgical treatment. This is still the mainstay of periodontal treatment. Adjunctive antimicrobial treatments, both systemic and local delivery, are becoming more sophisticated and useful in the treatment of recurrent periodontitis. Also very promising are adjunctive treatments that modulate the host response and decrease levels of destructive pro-inflammatory cytokines or matrix metalloproteinases. Smoking is a major risk factor for periodontitis and has a profound impact on the progression of periodontal bone and attachment loss. In the interest of improved periodontal health patients should be encouraged to stop smoking. Finally bacterial endotoxins that stimulate the release of pro-inflammatory cytokines can have systemic effects and may lead to pre-term, low birthweight babies, and cardiovascular diseases such as atherosclerosis, myocardial infarction and stroke. Health professionals need to be cognisant of the effect dental health can have on systemic diseases and refer for treatment when appropriate to ensure that optimum oral and systemic health is achieved for their patients. PMID:12465998

  14. Minimal intervention dentistry II: part 6. Microscope and microsurgical techniques in periodontics.

    PubMed

    Sitbon, Y; Attathom, T

    2014-05-01

    Different aspects of treatment for periodontal diseases or gingival problems require rigorous diagnostics. Magnification tools and microsurgical instruments, combined with minimally invasive techniques can provide the best solutions in such cases. Relevance of treatments, duration of healing, reduction of pain and post-operative scarring have the potential to be improved for patients through such techniques. This article presents an overview of the use of microscopy in periodontics, still in the early stages of development. PMID:24809564

  15. Early-onset acquired epileptic aphasia (Landau-Kleffner syndrome, LKS) and regressive autistic disorders with epileptic EEG abnormalities: the continuing debate.

    PubMed

    Deonna, Thierry; Roulet-Perez, Eliane

    2010-10-01

    Early-onset acquired epileptic aphasia (Landau-Kleffner syndrome) may present as a developmental language disturbance and the affected child may also exhibit autistic features. Landau-Kleffner is now seen as the rare and severe end of a spectrum of cognitive-behavioural symptoms that can be seen in idiopathic (genetic) focal epilepsies of childhood, the benign end being the more frequent typical rolandic epilepsy. Several recent studies show that many children with rolandic epilepsy have minor developmental cognitive and behavioural problems and that some undergo a deterioration (usually temporary) in these domains, the so-called "atypical" forms of the syndrome. The severity and type of deterioration correlate with the site and spread of the epileptic spikes recorded on the electroencephalogram within the perisylvian region, and continuous spike-waves during sleep (CSWS) frequently occur during this period of the epileptic disorder. Some of these children have more severe preexisting communicative and language developmental disorders. If early stagnation or regression occurs in these domains, it presumably reflects epileptic activity in networks outside the perisylvian area, i.e. those involved in social cognition and emotions. Longitudinal studies will be necessary to find out if and how much the bioelectrical abnormalities play a causal role in these subgroup of children with both various degrees of language and autistic regression and features of idiopathic focal epilepsy. One has to remember that it took nearly 40 years to fully acknowledge the epileptic origin of aphasia in Landau-Kleffner syndrome and the milder acquired cognitive problems in rolandic epilepsies. PMID:20637551

  16. 12/15-Lipoxygenase Is Required for the Early Onset of High Fat Diet-Induced Adipose Tissue Inflammation and Insulin Resistance in Mice

    PubMed Central

    Sears, Dorothy D.; Miles, Philip D.; Chapman, Justin; Ofrecio, Jachelle M.; Almazan, Felicidad; Thapar, Divya; Miller, Yury I.

    2009-01-01

    Background Recent understanding that insulin resistance is an inflammatory condition necessitates searching for genes that regulate inflammation in insulin sensitive tissues. 12/15-lipoxygenase (12/15LO) regulates the expression of proinflammatory cytokines and chemokines and is implicated in the early development of diet-induced atherosclerosis. Thus, we tested the hypothesis that 12/15LO is involved in the onset of high fat diet (HFD)-induced insulin resistance. Methodology/Principal Findings Cells over-expressing 12/15LO secreted two potent chemokines, MCP-1 and osteopontin, implicated in the development of insulin resistance. We assessed adipose tissue inflammation and whole body insulin resistance in wild type (WT) and 12/15LO knockout (KO) mice after 2–4 weeks on HFD. In adipose tissue from WT mice, HFD resulted in recruitment of CD11b+, F4/80+ macrophages and elevated protein levels of the inflammatory markers IL-1?, IL-6, IL-10, IL-12, IFN?, Cxcl1 and TNF?. Remarkably, adipose tissue from HFD-fed 12/15LO KO mice was not infiltrated by macrophages and did not display any increase in the inflammatory markers compared to adipose tissue from normal chow-fed mice. WT mice developed severe whole body (hepatic and skeletal muscle) insulin resistance after HFD, as measured by hyperinsulinemic euglycemic clamp. In contrast, 12/15LO KO mice exhibited no HFD-induced change in insulin-stimulated glucose disposal rate or hepatic glucose output during clamp studies. Insulin-stimulated Akt phosphorylation in muscle tissue from HFD-fed mice was significantly greater in 12/15LO KO mice than in WT mice. Conclusions These results demonstrate that 12/15LO mediates early stages of adipose tissue inflammation and whole body insulin resistance induced by high fat feeding. PMID:19787041

  17. Constitutive promoter methylation of BRCA1 and RAD51C in patients with familial ovarian cancer and early-onset sporadic breast cancer

    PubMed Central

    Hansmann, Tamara; Pliushch, Galyna; Leubner, Monika; Kroll, Patricia; Endt, Daniela; Gehrig, Andrea; Preisler-Adams, Sabine; Wieacker, Peter; Haaf, Thomas

    2012-01-01

    Genetic defects in breast cancer (BC) susceptibility genes, most importantly BRCA1 and BRCA2, account for ?40% of hereditary BC and ovarian cancer (OC). Little is known about the contribution of constitutive (soma-wide) epimutations to the remaining cases. We developed bisulfite pyrosequencing assays to screen >600 affected BRCA1/BRCA2 mutation-negative patients from the German Consortium for Hereditary Breast and Ovarian Cancer for constitutive hypermethylation of ATM, BRCA1, BRCA2, RAD51C, PTEN and TP53 in blood cells. In a second step, patients with ?6% promoter methylation were analyzed by bisulfite plasmid sequencing to demonstrate the presence of hypermethylated alleles (epimutations), indicative of epigenetic gene silencing. Altogether we identified nine (1.4%) patients with constitutive BRCA1 and three (0.5%) with RAD51C hypermethylation. Epimutations were found in both sporadic cases, in particular in 2 (5.5%) of 37 patients with early-onset BC, and familial cases, in particular 4 (10%) of 39 patients with OC. Hypermethylation was always confined to one of the two parental alleles in a subset (12–40%) of the analyzed cells. Because epimutations occurred in cell types from different embryonal layers, they most likely originated in single cells during early somatic development. We propose that analogous to germline genetic mutations constitutive epimutations may serve as the first hit of tumor development. Because the role of constitutive epimutations in cancer development is likely to be largely underestimated, future strategies for effective testing of susceptibility to BC and OC should include an epimutation screen. PMID:22843497

  18. Identification of the rare compound heterozygous variants in the NEB gene in a Korean family with intellectual disability, epilepsy and early-childhood-onset generalized muscle weakness.

    PubMed

    Jin, Hyun-Seok; Lee, Jong-Bin; Kim, Kyung; Lee, Ki-Young; Choi, Vit-Na; Kim, Jong-Soo; Jeong, Seon-Yong; Yim, Shin-Young

    2014-12-01

    We examined a Korean family with complex phenotypes characterized by intellectual disability, epilepsy and early-childhood-onset generalized muscle weakness. Since we did not find any abnormality using several conventional genetic tests for detection of chromosomal aberrations, gene copy number variations and mitochondrial gene mutations, we aimed to identify disease-causing genetic alteration(s) in this family. We conducted whole-exome sequencing (WES) in this family. After filtering the WES data, we compared five exome sequences of two affected siblings, one unaffected sibling and the unaffected parents, and we determined the allele frequency of the identified variants in an Asian population. Finally, we selected one candidate variant pair which is unique in the patients and corresponds to an autosomal recessive genetic model. The two affected siblings had the same compound heterozygous variation in the NEB gene encoding nebulin, which was composed of two different missense variants: c.2603T>C (p.L868P) in exon 27 and c.21340C>T (p.R7114W) in exon 143. We confirmed these variations by Sanger sequencing. On the basis of the fundamental role of nebulin in the brain and skeletal muscles, we concluded that this compound heterozygous NEB variation may be a sound candidate for the disease-causing mutation in this family. Since the patients are characterized by generalized muscle weakness together with neurodevelopmental phenotypes, it is suggested that NEB mutations could manifest more diverse phenotypes than those previously described. PMID:25296583

  19. Clinical effectiveness of early treatment with hyperbaric oxygen therapy for severe late-onset hemorrhagic cystitis after hematopoietic stem cell transplantation in pediatric patients.

    PubMed

    Zama, Daniele; Masetti, Riccardo; Vendemini, Francesca; Di Donato, Ferruccio; Morelli, Alessandra; Prete, Arcangelo; Pession, Andrea

    2013-02-01

    HC is a possible cause of morbidity and extended hospitalization after HSCT. Recent studies have reported the efficiency of HOT in adult patients who underwent allogeneic HSCT, but data in children are scarce. We report our single center experience with HOT in late-onset HC after HSCT. Treatment with HOT consisted of daily sessions of breathing 100% O(2) for a total of 75 min in the hyperbaric chamber with a minimum of eight sessions. HOT had been associated with a concomitant treatment with oral oxybutynin, hyperhydration and/or irrigation of the bladder through the catheter. Cidofovir had been administered based on the demonstration of viral infection. Between 2004 and 2011, 10 patients developed severe HC after a median of 26 days after HSCT. HOT was started after a median of six days since the clinical diagnosis of HC. After a median of 10 sessions of HOT, seven of 10 patients were in complete remission. HOT is a well-tolerated procedure also in the pediatric setting. The early start of HOT might be effective in the treatment of HC offering advantages in terms of duration of symptoms and hospitalization. PMID:23230825

  20. A rare association of early-onset inclusion body myositis, rheumatoid arthritis and autoimmune thyroiditis: a case report and literature review

    PubMed Central

    Clerici, Angelo Maurizio; Bono, Giorgio; Delodovici, Maria Luisa; Azan, Gaetano; Cafasso, Giuseppina; Micieli, Giuseppe

    2013-01-01

    Summary Sporadic inclusion body myositis (sIBM) is a slowly progressive, red-rimmed vacuolar myopathy leading to muscular atrophy and progressive weakness; it predominantly affects males older than fifty years, and is resistant to immunotherapy. It has been described in association with immuno-mediated thrombocytopenic purpura, multiple sclerosis, connective tissue disorders and, occasionally, rheumatoid arthritis. A 37-year-old man with longstanding rheumatoid arthritis and autoimmune thyroiditis with hypothyroidism was referred to us with slowly progressive, diffuse muscle weakness and wasting, which had initially involved the volar finger flexors, and subsequently also the ankle dorsiflexors and knee extensors. Needle electromyography showed typical myopathic motor unit potentials, fibrillation and positive sharp waves with normal nerve conduction studies. Quadriceps muscle biopsy was suggestive of sIBM. Considering data published in the literature, this case may be classified as an early-onset form. The patient was treated with long-term intravenous immunoglobulin and obtained a substantial stabilization of his muscle strength. PMID:24125563

  1. Combination of PAPPA, fhCG?, AFP, PlGF, sTNFR1, and Maternal Characteristics in Prediction of Early-onset Preeclampsia

    PubMed Central

    Yliniemi, Anna; Makikallio, Kaarin; Korpimaki, Teemu; Kouru, Heikki; Marttala, Jaana; Ryynanen, Markku

    2015-01-01

    OBJECTIVE To evaluate the efficacy of first-trimester markers—pregnancy-associated plasma protein A (PAPPA), free human chorionic gonadotropin ? (fhCG?), alpha-fetoprotein (AFP), placental growth factor (PlGF), and soluble tumor necrosis factor receptor-1 (sTNFR1) together with maternal characteristics (MC) for prediction of early-onset preeclampsia (EOPE). METHODS During 2005–2010, the abovementioned biomarkers were analyzed with logistic regression analysis in 64 EOPE and 752 control subjects to determine whether these biomarkers separately and in combination with MC would predict development of EOPE. RESULTS PAPPA, fhCG?, and PlGF levels were lower, whereas AFP and sTNFR1 levels were higher in mothers with EOPE compared to controls. The combination of all markers with MC (age, weight, and smoking status) detected 48% of the mothers with EOPE, with a 10% false-positive rate (FPR). CONCLUSIONS First-trimester maternal serum levels of PAPPA, fhCG?, AFP, PlGF, and sTNFR1, together with MC, are predictive of development of subsequent EOPE. These markers, along with MC, form a suitable panel for predicting EOPE.

  2. A case of cauda equina syndrome in early-onset chronic inflammatory demyelinating polyneuropathy clinically similar to charcot-marie-tooth disease type 1.

    PubMed

    Lee, Seung Eun; Park, Seung Won; Ha, Sam Yeol; Nam, Taek Kyun

    2014-06-01

    To present a case of cauda equina syndrome (CES) caused by chronic inflammatory demyelinating polyneuropathy (CIDP) which seemed clinically similar to Charcot-Marie-Tooth disease type1 (CMT1). CIDP is an immune-mediated polyneuropathy, either progressive or relapsing-remitting. It is a non-hereditary disorder characterized by symmetrical motor and sensory deficits. Rarely, spinal nerve roots can be involved, leading to CES by hypertrophic cauda equina. A 34-year-old man presented with low back pain, radicular pain, bilateral lower-extremity weakness, urinary incontinence, and constipation. He had had musculoskeletal deformities, such as hammertoes and pes cavus, since age 10. Lumbar spine magnetic resonance imaging showed diffuse thickening of the cauda equina. Electrophysiological testing showed increased distal latency, conduction blocks, temporal dispersion, and severe nerve conduction velocity slowing (3 m/s). We were not able to find genetic mutations at the PMP 22, MPZ, PRX, and EGR2 genes. The pathologic findings of the sural nerve biopsy revealed thinly myelinated nerve fibers with Schwann cells proliferation. We performed a decompressive laminectomy, intravenous IgG (IV-IgG) and oral steroid. At 1 week after surgery, most of his symptoms showed marked improvements except foot deformities. There was no relapse or aggravation of disease for 3 years. We diagnosed the case as an early-onset CIDP with cauda equine syndrome, whose initial clinical findings were similar to those of CMT1, and successfully managed with decompressive laminectomy, IV-IgG and oral steroid. PMID:25237436

  3. A Case of Cauda Equina Syndrome in Early-Onset Chronic Inflammatory Demyelinating Polyneuropathy Clinically Similar to Charcot-Marie-Tooth Disease Type 1

    PubMed Central

    Lee, Seung Eun; Ha, Sam Yeol; Nam, Taek Kyun

    2014-01-01

    To present a case of cauda equina syndrome (CES) caused by chronic inflammatory demyelinating polyneuropathy (CIDP) which seemed clinically similar to Charcot-Marie-Tooth disease type1 (CMT1). CIDP is an immune-mediated polyneuropathy, either progressive or relapsing-remitting. It is a non-hereditary disorder characterized by symmetrical motor and sensory deficits. Rarely, spinal nerve roots can be involved, leading to CES by hypertrophic cauda equina. A 34-year-old man presented with low back pain, radicular pain, bilateral lower-extremity weakness, urinary incontinence, and constipation. He had had musculoskeletal deformities, such as hammertoes and pes cavus, since age 10. Lumbar spine magnetic resonance imaging showed diffuse thickening of the cauda equina. Electrophysiological testing showed increased distal latency, conduction blocks, temporal dispersion, and severe nerve conduction velocity slowing (3 m/s). We were not able to find genetic mutations at the PMP 22, MPZ, PRX, and EGR2 genes. The pathologic findings of the sural nerve biopsy revealed thinly myelinated nerve fibers with Schwann cells proliferation. We performed a decompressive laminectomy, intravenous IgG (IV-IgG) and oral steroid. At 1 week after surgery, most of his symptoms showed marked improvements except foot deformities. There was no relapse or aggravation of disease for 3 years. We diagnosed the case as an early-onset CIDP with cauda equine syndrome, whose initial clinical findings were similar to those of CMT1, and successfully managed with decompressive laminectomy, IV-IgG and oral steroid. PMID:25237436

  4. Effects of different manual periodontal probes on periodontal measurements

    PubMed Central

    Holtfreter, Birte; Alte, Dietrich; Schwahn, Christian; Desvarieux, Moïse; Kocher, Thomas

    2013-01-01

    Aim To quantify the digit preference effect for three manual periodontal probes and to calculate correction values to enable comparison of studies with equal recording protocols, but different periodontal probes. Material and Methods A prospective in vivo crossover study was conducted with a six-sequence three-period design. Six examiners assessed attachment loss (AL), probing pocket depth (PD) and gingiva height (GH) at four surfaces, full-mouth, in six generally healthy subjects using three manual probes: PCP11 (3-3-3-2 mm increments), PCP2 (2 mm increments), and PCPUNC15 (1 mm increments). Results Distributions of AL, PD and GH differed between probes (p < 0.001). Compared with PCPUNC15, periodontal measurements coinciding with probe markings of PCP11 and PCP2, respectively, were preferentially named by examiners. Digit preference was most pronounced for PD, but less for AL and GH. In multilevel models, PD differed significantly between all three probes (p < 0.05); probe- and examiner-related effects were also observed for AL and GH. Correction values for pairwise combinations of probes were determined. Conclusions We provided empirical evidence and quantified the effect of probe type on periodontal measurements. Differences in probe type should be considered when comparing periodontal data within and between epidemiological studies and appropriate corrections, provided here, should be applied. PMID:22924328

  5. Young-Onset Dementia

    PubMed Central

    Kuruppu, Dulanji K; Matthews, Brandy R

    2014-01-01

    Young-onset dementia (YOD) is an neurological syndrome that affects behavior and cognition of patients younger than 65 years of age. Although frequently misdiagnosed, a systematic approach, reliant upon attainment of detailed medical history, collateral history from an informant, neuropsychological testing, laboratory studies, and neuroimaging, may facilitate earlier and more accurate diagnosis with subsequent intervention. The differential diagnosis of YOD is extensive and includes early-onset forms of adult neurodegenerative conditions including Alzheimer's disease, vascular dementia, frontotemporal dementia, Lewy body dementias, Huntington's disease, and prion disease. Late-onset forms of childhood neurodegenerative conditions may also present as YOD and include mitochondrial disorders, lysosomal storage disorders, and leukodystrophies. Potentially reversible etiologies including inflammatory disorders, infectious diseases, toxic/metabolic abnormalities, transient epileptic amnesia, obstructive sleep apnea, and normal pressure hydrocephalus also represent important differential diagnostic considerations in YOD. This review will present etiologies, diagnostic strategies, and options for management of YOD with comprehensive summary tables for clinical reference. PMID:24234358

  6. Childhood Onset Schizophrenia: Clinical Features, Course and Outcome

    ERIC Educational Resources Information Center

    Sood, Mamta; Kattimani, Shivanand

    2008-01-01

    Schizophrenia in children is diagnosed by using adult criteria. Based on the age of onset, patients with childhood onset schizophrenia (COS) are subdivided into those with very early onset (before age 12-14 years) and those with early onset (between 14-17 years). The prevalence of COS is reported to be 1 in 10,000 before the age of 12 years;…

  7. Coupled Low-temperature Thermochronometry and Ar Dating of Fault Gouge: New Evidence of Early Onset (~45 Ma) of Deformation Along the Northeastern Margin of the Tibetan Plateau

    NASA Astrophysics Data System (ADS)

    Duvall, A.; Clark, M.; van der Pluijm, B.; Li, C.; Farley, K.

    2008-12-01

    Understanding complex interactions among climate, erosion and tectonics is hampered by a lack of independent measure of faulting, erosion, and elevation change related to mountain building. The most common approach to measure erosion rates in compressional settings is by use of low-temperature thermochronometry; however correlation of erosion events with fault motion is complicated by climatic forcing. A separate technique, Ar/Ar dating of clays in fault gouge, provides direct timing of fault activity, though whether this age represents fault onset, end of fault motion, or some stage in between is poorly understood. We present He cooling and fault gouge ages from a single locality in northeastern Tibet in order to relate timing of fault motion with the erosion record and thermal conditions of hanging wall rocks. The West Qinling reverse fault is one of the longest, most continuous faults in northeastern Tibet. Apatite (U-Th)/He cooling ages spanning ~3 km of structural depth within the hanging wall of this fault show old ages/little exhumation in the Jurassic and early Cenozoic followed by an increase in apparent erosion rate at ~45 Ma that was sustained until at least 13 Ma. Timing of brittle faulting along this structure is determined by dating several size fractions of clay from fault gouge that represent variable populations of two illite polytypes: detrital clay (2M1) derived from wall rock and authigenic clay (1Md) formed in the fault zone during faulting. Preliminary results show that the purely authigenic component formed at ~50-45 Ma and that the purely detrital component formed at ~230 Ma; thus suggesting Middle Eocene faulting and a Middle Triassic age of the source area of wall rocks. Coupled results from the two datasets supports the interpretation that 1) the W. Qinling fault initiated at 45 Ma and continued until at least Middle Miocene time and 2) formation of authigenic clay in the fault zone occurred at temperatures of ~150° C. Lack of overprinting of younger clay ages at this site likely indicates that rocks were out of the thermal window for authigenic clay formation during later faulting episodes. Paired together, thermochronometry and clay dating in fault gouge provide an unambiguous interpretation of fault history difficult to infer from the erosion record or fault age alone. Results from this study emphasize the value of this new approach and provide the first direct evidence of Middle Eocene compressional fault motion in northeastern Tibet, which we relate to onset of Indo-Asian collision.

  8. ORIGINAL ARTICLE Onset-related differences in neural substrates of tinnitus-related

    E-print Network

    O'Toole, Alice J.

    ORIGINAL ARTICLE Onset-related differences in neural substrates of tinnitus-related distress: the anterior cingulate cortex in late-onset tinnitus, and the frontal cortex in early-onset tinnitus Jae electroencephalography (qEEG) findings of 28 late-onset tinnitus (LOT) and 29 early-onset tinnitus (EOT) (mean onset age

  9. Diagnosis of Periodontal Diseases by Biomarkers

    Microsoft Academic Search

    Jun-Ichi Kido; Mami Hino; Mika Bando; Yuka Hiroshima

    2009-01-01

    Many middle aged and old persons take periodontal diseases that mainly cause teeth loss and result in some systemic diseases. The prevention of periodontal diseases is very important for oral and systemic health, but the present diagnostic examination is not fully objective and suitable. To diagnose periodontal diseases exactly, some biomarkers shown inflammation, tissue degradation and bone resorption, in gingival

  10. Lessons learned and unlearned in periodontal microbiology

    PubMed Central

    Teles, Ricardo; Teles, Flavia; Frias-Lopez, Jorge; Paster, Bruce; Haffajee, Anne

    2013-01-01

    Periodontal diseases are initiated by bacterial species living in polymicrobial biofilms at or below the gingival margin and progress largely as a result of the inflammation initiated by specific subgingival species. In the past few decades, efforts to understand the microbiota of periodontal diseases have led to an exponential increase in information about biofilms associated with periodontal health and disease. In fact, the oral microbiota is one of the best characterized microbiomes that colonize the human body. Despite this increased knowledge, one has to ask if our fundamental concepts of the etiology and pathogenesis of periodontal diseases have really changed. In this chapter we will review how our comprehension of the structure and function of the subgingival microbiota evolved over the years in search of lessons learned and unlearned in periodontal microbiology. More specifically, this review focuses on: 1) how the data obtained through molecular techniques has impacted our knowledge of the etiology of periodontal infections; 2) the potential role of viruses in the etiopathogenesis of periodontal diseases; 3) how concepts of microbial ecology have expanded our understanding of host microbial interactions that might lead to periodontal diseases; 4) the role of inflammation in the pathogenesis of periodontal diseases; and 5) the impact of these evolving concepts on treatment and preventive approaches to periodontal infections. We will conclude by reviewing how novel systems biology approaches promise to unravel new details of the pathogenesis of periodontal diseases and, hopefully, lead to a better understanding of periodontal disease mechanisms. PMID:23574465

  11. Periodontal (Gum) Disease Causes, Symptoms, and Treatments

    E-print Network

    Bandettini, Peter A.

    Periodontal (Gum) Disease Causes, Symptoms, and Treatments U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health #12;Periodontal (Gum) Disease If you have been told you have periodontal (gum) disease, you're not alone. Many adults in the U.S. currently have some form of the disease

  12. Gene expression in periodontal tissues following treatment

    Microsoft Academic Search

    Thomas Beikler; Ulrike Peters; Karola Prior; Martin Eisenacher; Thomas F Flemmig

    2008-01-01

    BACKGROUND: In periodontitis, treatment aimed at controlling the periodontal biofilm infection results in a resolution of the clinical and histological signs of inflammation. Although the cell types found in periodontal tissues following treatment have been well described, information on gene expression is limited to few candidate genes. Therefore, the aim of the study was to determine the expression profiles of

  13. Links demystified: Periodontitis and cancer.

    PubMed

    Pendyala, Gowri; Joshi, Saurabh; Chaudhari, Shantanu; Gandhage, Dhananjay

    2013-11-01

    Cancer is marked by the uncontrolled growth of cells, tissue invasion and metastasis to various organs via the circulatory and lymphatic systems. Recent data have expanded the concept that inflammation is a critical component of tumor progression. Many cancers arise from sites of infection, chronic irritation, and inflammation. The tumor microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival, and migration. Periodontal disease, a chronic inflammatory condition is characterized by an oral bacterial infection leading to inflammation within the supporting tissues of the teeth, which often leads to the destruction of the periodontal tissues and alveolar bone that support the teeth. This oral inflammation often has systemic effects leading to an increased concentration of circulating inflammatory markers with the severity of disease being correlated directly with levels of serum inflammatory markers. Periodontal infection has been linked to organ and systemic diseases. There is documented evidence of significant associations between cancer of the lung, kidney, pancreas, hematological and oral cancers, and periodontal disease. This articles reviews and summarizes the possible biological mechanisms involved between periodontal infection and cancer. PMID:24379856

  14. Epigenetic biomarkers: a step forward for understanding periodontitis.

    PubMed

    Lindroth, Anders M; Park, Yoon Jung

    2013-06-01

    Periodontitis is a common oral disease that is characterized by infection and inflammation of the tooth supporting tissues. While its incidence is highly associated with outgrowth of the pathogenic microbiome, some patients show signs of predisposition and quickly fall into recurrence after treatment. Recent research using genetic associations of candidates as well as genome-wide analysis highlights that variations in genes related to the inflammatory response are associated with an increased risk of periodontitis. Intriguingly, some of the genes are regulated by epigenetic modifications, supposedly established and reprogrammed in response to environmental stimuli. In addition, the treatment with epigenetic drugs improves treatment of periodontitis in a mouse model. In this review, we highlight some of the recent progress identifying genetic factors associated with periodontitis and point to promising approaches in epigenetic research that may contribute to the understanding of molecular mechanisms involving different responses in individuals and the early detection of predispositions that may guide in future oral treatment and disease prevention. PMID:23837125

  15. Epigenetic biomarkers: a step forward for understanding periodontitis

    PubMed Central

    Lindroth, Anders M.

    2013-01-01

    Periodontitis is a common oral disease that is characterized by infection and inflammation of the tooth supporting tissues. While its incidence is highly associated with outgrowth of the pathogenic microbiome, some patients show signs of predisposition and quickly fall into recurrence after treatment. Recent research using genetic associations of candidates as well as genome-wide analysis highlights that variations in genes related to the inflammatory response are associated with an increased risk of periodontitis. Intriguingly, some of the genes are regulated by epigenetic modifications, supposedly established and reprogrammed in response to environmental stimuli. In addition, the treatment with epigenetic drugs improves treatment of periodontitis in a mouse model. In this review, we highlight some of the recent progress identifying genetic factors associated with periodontitis and point to promising approaches in epigenetic research that may contribute to the understanding of molecular mechanisms involving different responses in individuals and the early detection of predispositions that may guide in future oral treatment and disease prevention. PMID:23837125

  16. Symptoms of Eating Disorders and Depression in Emerging Adults with Early-Onset, Long-Duration Type 1 Diabetes and Their Association with Metabolic Control

    PubMed Central

    Bächle, Christina; Lange, Karin; Stahl-Pehe, Anna; Castillo, Katty; Scheuing, Nicole; Holl, Reinhard W.; Giani, Guido; Rosenbauer, Joachim

    2015-01-01

    Background This study analyzed the prevalence of and association between symptoms of eating disorders and depression in female and male emerging adults with early-onset, long-duration type 1 diabetes and investigated how these symptoms are associated with metabolic control. Methods In a nationwide population-based survey, 211 type 1 diabetes patients aged 18-21 years completed standardized questionnaires, including the SCOFF questionnaire for eating disorder symptoms and the Patient Health Questionnaire (PHQ-9) for symptoms of depression and severity of depressive symptoms (PHQ-9 score). Multiple linear and logistic regression models were used to analyze the association between eating disorder and depressive symptoms and their associations with HbA1c. Results A total of 30.2% of the women and 9.5% of the men were screening positive for eating disorders. The mean PHQ-9 score (standard deviation) was 5.3 (4.4) among women and 3.9 (3.6) among men. Screening positive for an eating disorder was associated with more severe depressive symptoms among women (?women 3.8, p<0.001). However, neither eating disorder symptoms nor severity of depressive symptoms were associated with HbA1c among women, while HbA1c increased with the severity of depressive symptoms among men (?men 0.14, p=0.006). Conclusions Because of the high prevalence of eating disorder and depressive symptoms, their interrelationship, and their associations with metabolic control, particularly among men, regular mental health screening is recommended for young adults with type 1 diabetes. PMID:26121155

  17. Salmonella enterica Induces Joint Inflammation and Expression of Interleukin-17 in Draining Lymph Nodes Early after Onset of Enterocolitis in Mice

    PubMed Central

    Sarnacki, Sebastián Hernán; Vázquez, María Victoria; Gartner, Alejandra Sonia; Giacomodonato, Mónica Nancy

    2012-01-01

    In developing countries, one-third of reactive arthritis (ReA) cases are associated with Salmonella enterocolitis; nevertheless, there is no animal model for studying this pathology. Here we induced a self-limiting Salmonella enterica serovar Enteritidis enterocolitis in mice to analyze the onset of ReA. BALB/c mice received orally 20 ?g of streptomycin 24 h before intragastric inoculation of a low dose (3 × 103 to 4 × 103 CFU) of S. Enteritidis. In response to Salmonella infection, a 30-fold increase in the expression of interleukin-17 (IL-17), measured by quantitative PCR, was observed in mesenteric lymph nodes 5 days postinfection. At this time synovitis was already evident, and concomitantly, a significant increase in joint tumor necrosis factor alpha (TNF-?) was detected by enzyme-linked immunosorbent assay (ELISA). The early development of joint lesions was accompanied by an increased expression of IL-17 in inguinal and popliteal lymph nodes. Infection with 107 CFU of an isogenic ?invG mutant bearing a defective type III secretion system of Salmonella encoded in the pathogenicity island 1 apparatus (TTSS-1) induced enterocolitis histologically similar to that triggered by the wild-type strain. Interestingly, despite the higher infective dose used, the mutant did not trigger intestinal IL-17. Moreover, no synovitis was observed in mice suffering ?invG enterocolitis. Neutralization of IL-17 in mice infected with S. Enteritidis prevented both synovitis and the increment of TNF-? in the joints, suggesting that IL-17 participates in the generation of Salmonella-induced ReA through the induction of TNF-? in the joints. PMID:22493084

  18. White matter fractional anisotropy over two time points in early onset schizophrenia and adolescent cannabis use disorder: A naturalistic diffusion tensor imaging study.

    PubMed

    Epstein, Katherine A; Kumra, Sanjiv

    2015-04-30

    Recurrent exposure to cannabis in adolescence increases the risk for later development of psychosis, but there are sparse data regarding the impact of cannabis use on brain structure during adolescence. This pilot study investigated the effect of cannabis use disorder (CUD) upon white matter fractional anisotropy (WM FA) values in non-psychotic treatment-seeking adolescents relative to adolescents with early onset schizophrenia-spectrum disorders (EOSS) and to healthy control (HC) participants. Diffusion tensor imaging (DTI) and tractography methods were used to examine fractional anisotropy (FA) of the cingulum bundle, superior longitudinal fasciculus (SLF), corticospinal tract (CST), inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF) and uncinate fasciculus in adolescents with EOSS (n=34), CUD (n=19) and HC (n=29). Participants received DTI and substance use assessments at baseline and at 18-month follow-up. Using multivariate analysis of variance, a significant main effect of diagnostic group was observed. Post-hoc testing revealed that adolescents with CUD showed an altered change in FA values in the left ILF and in the left IFOF (trend level) compared with HC adolescents. Greater consumption of cannabis during the inter-scan interval predicted a greater decrease in left ILF FA in CUD. These preliminary longitudinal data suggest that heavy cannabis use during adolescence, or some factor associated with cannabis use, is associated with an altered change in WM FA values in a fiber bundle that has been implicated in the pathophysiology of EOSS (i.e., the left ILF). Additional studies are needed to clarify the clinical significance of these findings. PMID:25779033

  19. Risk Factors for Early Onset of Catheter-Related Bloodstream Infection in an Intensive Care Unit in China: A Retrospective Study

    PubMed Central

    Tao, Fuzheng; Jiang, Ronglin; Chen, Yingzi; Chen, Renhui

    2015-01-01

    Background Catheter-related bloodstream infection (CRBSI) is a life-threatening condition encountered in patients with long-term central venous catheter (CVC) indwelling. The objective was to investigate the clinical characteristics, treatment, and prognosis of CRBSI in the intensive care unit (ICU) in a Chinese center, as well as the risk factors for early CRBSI. Material/Methods A total of 73 CRBSI patients were retrospectively studied in relation to patients’ clinical and epidemiological data, microbiological culture, and treatment. Patients were treated at the Taizhou Hospital of Integrated Traditional Chinese and Western Medicine in Zhejiang (Zhejiang Wenlin, China) between January 2010 and December 2012. Results In this Chinese center, the most common pathogens were Gram-positive cocci, followed by Gram-negative bacilli and fungi. A high prevalence of antibiotic-resistant pathogens was detected, and a higher percentage of non-Candida albicans spp. was observed. Multivariate analysis showed that an acute physiology and chronic health evaluation II (APACHE II) score >20 and >3 types of underlying diseases were independent factors associated with CRBSI occurring within 14 days of CVC indwelling. Untimely CVC removal and/or inappropriate use of antibiotics led to significantly longer time to defervescence and time to negative conversion of blood culture (all P<0.05). Conclusions In this Chinese center, Gram-positive bacteria are predominantly detected in CRBSI. APACHE II score >20 and the presence of >3 types of diseases were associated with earlier CRBSI onset. Timely removal of CVC and appropriate use of antibiotics resulted in improved outcomes. PMID:25695128

  20. Recent approaches for the treatment of periodontitis.

    PubMed

    Jain, Nilu; Jain, Gaurav K; Javed, Shamama; Iqbal, Zeenat; Talegaonkar, Sushama; Ahmad, Farhan J; Khar, Roop K

    2008-11-01

    Periodontal disease is a localised inflammatory response caused by the infection of a periodontal pocket arising from the accumulation of subgingival plaque. Periodontal disease has been considered as a possible risk factor for other systemic diseases such as cardiovascular diseases and pre-term low birth weight infants. Advances in understanding the aetiology, epidemiology and microbiology of periodontal pocket flora have revolutionised the therapeutic strategies for the management of periodontal disease progression. This review summarises the recent developments in the field of intra-pocket drug delivery systems and identifies areas where further research may lead to a clinically effective intra-pocket delivery system. PMID:18789399

  1. Multifactorial Relationship of Obesity and Periodontal Disease

    PubMed Central

    Mahendra, Jaideep

    2014-01-01

    Obesity is a chronic disease of mutifactorial origin, where there is increase in body fat. Periodontitis is an inflammatory disease of tooth supporting tissues resulting in destruction of periodontal ligament and alveolar bone. Periodontitis and obesity are both chronic health problems and the literature supports this association. A hyperinflammatory state observed in obesity is proposed as a mechanism to explain this association. This low grade inflammation in obese subjects triggers the worsening of non transmissible chronic diseases like periodontitis. So the aim of this article is to get the overview of association between adipose tissue derived cytokines and periodontal disease. PMID:24959524

  2. Guided periodontal tissue regeneration (GPTR): an update.

    PubMed

    Quiñones, C R; Casellas, J C; Caffesse, R G

    1996-03-01

    Periodontal therapy has three primary objectives--elimination of etiologic factors, repair or regeneration of the lost attachment apparatus, and prevention of further periodontal breakdown. Significant progress has occurred in the area of surgical periodontal therapy during the last two decades. Periodontal regeneration has become a viable treatment option utilizing the principles of guided tissue regeneration. The learning objective of this article is to review the biologic rationale, the various barrier materials currently available, and the surgical techniques for guided periodontal tissue regeneration procedures using nonresorbable and resorbable barriers, with and without bone grafting materials. PMID:9028290

  3. Role of Autoimmune Responses in Periodontal Disease

    PubMed Central

    Nair, Soumya; Faizuddin, Mohamed; Dharmapalan, Jayanthi

    2014-01-01

    Periodontal diseases are characterized by localized infections and inflammatory conditions that directly affect teeth supporting structures which are the major cause of tooth loss. Several studies have demonstrated the involvement of autoimmune responses in periodontal disease. Evidences of involvement of immunopathology have been reported in periodontal disease. Bacteria in the dental plaque induce antibody formation. Autoreactive T cells, natural killer cells, ANCA, heat shock proteins, autoantibodies, and genetic factors are reported to have an important role in the autoimmune component of periodontal disease. The present review describes the involvement of autoimmune responses in periodontal diseases and also the mechanisms underlying these responses. This review is an attempt to throw light on the etiopathogenesis of periodontal disease highlighting the autoimmunity aspect of the etiopathogenesis involved in the initiation and progression of the disease. However, further clinical trials are required to strengthen the role of autoimmunity as a cause of periodontal disease. PMID:24963400

  4. Multi-allelic haplotype association identifies novel information different from single-SNP analysis: A new protective haplotype in the LRP8 gene is against familial and early-onset CAD and MI

    PubMed Central

    Shen, Gong-Qing; Girelli, Domenico; Li, Lin; Olivieri, Oliviero; Martinelli, Nicola; Chen, Qiuyun; Topol, Eric J.; Wang, Qing K.

    2014-01-01

    Our previous studies identified a functional SNP, R952Q in the LRP8 gene, that was associated with increased platelet activation and familial and early-onset coronary artery disease (CAD) and myocardial infarction (MI) in American and Italian Caucasian populations. In this study, we analyzed four additional SNPs near R952Q (rs7546246, rs2297660, rs3737983, rs5177) to identify a specific LRP8 SNP haplotype that is associated with familial and early-onset CAD and MI. We employed a case–control association design involving 381 premature CAD and MI probands and 560 controls in GeneQuest, 441 individuals from 22 large pedigrees in GeneQuest II, and 248 MI patients with family history and 308 controls in an Italian cohort. Like R952Q, LRP8 SNPs rs7546246, rs2297660, rs3737983, and rs5177 were significantly associated with early-onset CAD/MI in both population-based and family-based association studies in GeneQuest. The results were replicated in the GeneQuest II family-based population and the Italian population. We then carried out a haplotype analysis for all five SNPs including R952Q. One common haplotype (TCCGC) was significantly associated with CAD (P = 4.0 × 10?11) and MI (P = 6.5 × 10?12) in GeneQuest with odds ratios of 0.53 and 0.42, respectively. The results were replicated in the Italian cohort (P = 0.004, OR = 0.71). The sib-TDT analysis also showed significant association between the TCCGC haplotype and CAD in GeneQuest II (P = 0.001). These results suggest that a common LRP8 haplotype TCCGC confers a significant protective effect on the development of familial, early-onset CAD and/or MI. PMID:23524007

  5. Multi-allelic haplotype association identifies novel information different from single-SNP analysis: a new protective haplotype in the LRP8 gene is against familial and early-onset CAD and MI.

    PubMed

    Shen, Gong-Qing; Girelli, Domenico; Li, Lin; Olivieri, Oliviero; Martinelli, Nicola; Chen, Qiuyun; Topol, Eric J; Wang, Qing K

    2013-05-25

    Our previous studies identified a functional SNP, R952Q in the LRP8 gene, that was associated with increased platelet activation and familial and early-onset coronary artery disease (CAD) and myocardial infarction (MI) in American and Italian Caucasian populations. In this study, we analyzed four additional SNPs near R952Q (rs7546246, rs2297660, rs3737983, rs5177) to identify a specific LRP8 SNP haplotype that is associated with familial and early-onset CAD and MI. We employed a case-control association design involving 381 premature CAD and MI probands and 560 controls in GeneQuest, 441 individuals from 22 large pedigrees in GeneQuest II, and 248 MI patients with family history and 308 controls in an Italian cohort. Like R952Q, LRP8 SNPs rs7546246, rs2297660, rs3737983, and rs5177 were significantly associated with early-onset CAD/MI in both population-based and family-based association studies in GeneQuest. The results were replicated in the GeneQuest II family-based population and the Italian population. We then carried out a haplotype analysis for all five SNPs including R952Q. One common haplotype (TCCGC) was significantly associated with CAD (P=4.0×10(-11)) and MI (P=6.5×10(-12)) in GeneQuest with odds ratios of 0.53 and 0.42, respectively. The results were replicated in the Italian cohort (P=0.004, OR=0.71). The sib-TDT analysis also showed significant association between the TCCGC haplotype and CAD in GeneQuest II (P=0.001). These results suggest that a common LRP8 haplotype TCCGC confers a significant protective effect on the development of familial, early-onset CAD and/or MI. PMID:23524007

  6. Improved prediction of early-onset coronary artery disease using APOE ?4, BChE-K, PPAR?2 Pro12 and ENOS T-786C in a polygenic model

    Microsoft Academic Search

    Bassam A. Nassar; Kenneth Rockwood; Susan A. Kirkland; Thomas P. Ransom; Sultan Darvesh; Kathleen MacPherson; David E. Johnstone; Blair J. O'Neill; Iqbal R. Bata; Pantelis Andreou; Julie S. Jeffery; Jafna L. Cox

    2006-01-01

    Objectives:Coronary artery disease (CAD) is often polygenic due to multiple mutations that contribute small effects to susceptibility. Since most prior studies only evaluated the contribution of single candidate genes, we therefore looked at a combination of genes in predicting early-onset CAD [apolipoprotein E (APOE) ?4, butyrylcholinesterase (BChE) K, peroxisome proliferator-activated receptor ?2 (PPAR?2) Pro12Ala and endothelial nitric oxide synthase (ENOS)

  7. Periodontal considerations in veneer cases.

    PubMed

    Peto, David

    2015-04-01

    Porcelain veneers are a minimally invasive technique to enhance patients' smiles. A crucial component in these cases is the supporting periodontal apparatus and its interaction with the restorations. This article addresses basic concepts such as biologic width, altered eruption patterns, appropriate gingival contouring and smile design to give practitioners the tools to diagnose, evaluate and treat cases successfully and predictably. PMID:25916012

  8. Novel Radiopaque UHMWPE Sublaminar Wires in a Growth-Guidance System for the Treatment of Early Onset Scoliosis: Feasibility in a Large Animal Study.

    PubMed

    Bogie, R; Roth, Ak; Faber, S; de Jong, Jja; Welting, Tjm; Willems, Pc; Arts, Jj; van Rhijn, Lw

    2014-09-29

    Study Design. In vivo analysis in an ovine model.Objective. To evaluate the feasibility of radiopaque UHMWPE sublaminar wires in a growth-guidance spinal system by assessing stability, biocompatibility and growth potential.Summary of Background Data. Several growth-guidance systems have been developed for the treatment of early onset scoliosis (EOS). The use of gliding pedicle screws and metal sublaminar wires during these procedures can cause metal-on-metal debris formation and neurological deficits. Novel radiopaque UHMWPE wires are introduced to safely facilitate longitudinal growth and provide stability in a growth-guidance system for EOS.Methods. Twelve immature sheep received posterior segmental spinal instrumentation; pedicle screws were inserted at L5 and radiopaque UHWMPE (bismuth trioxide) wires were passed sublaminarly at each level between L3 and T11 and fixed to dual cobalt-chromiun rods. Four age-matched, unoperated animals were evaluated to serve as a control group. Radiographs were taken to measure growth of the instrumented segment. After 24 weeks, the animals were sacrificed and the spines were harvested for histological evaluation and high resolution peripheral quantitative computed tomography (HR-pQCT) analysis.Results. No neurological deficits occurred and all instrumentation remained stable. One animal died from an unknown cause. Substantial growth occurred in the instrumented segments (L5-T11) in the intervention group (27± 2 mm), which was not significantly different to the control group, (30 ± 4mm, p = 0.42). HR-pQCT analysis clearly showed safe routing and fixation of the UHMWPE wires and instrumentation. Despite the noted growth, ectopic bone formation with the formation of bony bridges was observed in all animals. Histology revealed no evidence of chronic inflammation or wear debris.Conclusions. This study shows the first results of radiopaque UHMWPE sublaminar wires as part of a growth guidance spinal system. UHMWPE sublaminar wires facilitated near-normal longitudinal spinal growth. All instrumentation remained stable throughout follow-up; no wire breakage or loosening occurred and no adverse local tissue response to these wires was observed. PMID:25271492

  9. Clinical application of CO2 laser in periodontal treatment

    NASA Astrophysics Data System (ADS)

    Hayase, Yasuhiro

    1994-09-01

    CO2 lasers in particular are expected to have many dental applications because the CO2 laser beam exhibits strong tissue transpirative actions, such as instant coagulation, carbonization, and vaporization, and because its wavelength at 10.6 micrometers is fully absorbed by water so that the ability to make precise incisions with a high degree of safety is excellent, without damaging the deep tissues. However, clinical application of the CO2 laser has been slowed since a fiber which can conduct the laser beam to the oral cavity has only recently developed. This new fiber is an extremely flexible fiber with a minimum bending radius of 20 mm and utilizes pulse wave modes that have improved the handling characteristics in the mouth, and this has enabled us to apply the CO2 laser to a variety of periodontal conditions. The aim of this study was to evaluate the effectiveness of CO2 lasers for the early treatment of inflammation and pain relief of acute periodontitis, curettage of periodontal pockets, healing after excision of gingiva, and early improvement of gingivitis.

  10. Single nucleotide polymorphisms associated with aggressive periodontitis and severe chronic periodontitis in Japanese.

    PubMed

    Suzuki, Asami; Ji, Guijin; Numabe, Yukihiro; Muramatsu, Masaaki; Gomi, Kazuhiro; Kanazashi, Mikimoto; Ogata, Yorimasa; Shimizu, Emi; Shibukawa, Yoshihiro; Ito, Akiyo; Ito, Taichi; Sugaya, Akira; Arai, Takashi; Yamada, Satoru; Deguchi, Shinji; Kamoi, Kyuichi

    2004-05-01

    Periodontitis is a common inflammatory disease causing destruction of periodontal tissues. It is a multifactor disease involving genetic factors and oral environmental factors. To determine genetic risk factors associated with aggressive periodontitis or severe chronic periodontitis, single nucleotide polymorphisms (SNPs) in multiple candidate genes were investigated in Japanese. We studied 134 patients with aggressive periodontitis, 117 patients with severe chronic periodontitis, and 125 healthy volunteers without periodontitis, under case-control setting, and 310 SNPs in 125 candidate genes were genotyped. Association evaluation by Fisher's exact test (p < 0.01) revealed statistically significant SNPs in multiple genes, not only in inflammatory mediators (IL6ST and PTGDS, associated with aggressive periodontitis; and CTSD, associated with severe chronic periodontitis), but also in structural factors of periodontal tissues (COL4A1, COL1A1, and KRT23, associated with aggressive periodontitis; and HSPG2, COL17A1, and EGF, associated with severe chronic periodontitis). These appear to be good candidates as genetic factors for future study. PMID:15081423

  11. Periodontology: a clinical approach. 4. Periodontal surgery.

    PubMed

    Palmer, R M; Floyd, P D

    1995-04-22

    Results from comparative surgical studies have shown small differences between methods when evaluated over a few years post-surgically. Early interim results suggest that apical repositioning is more effective at reducing probing depth, replaced flaps (such as the modified Widman technique) offer slight advantages in terms of gain in clinical attachment, and procedures which involve extensive bone removal or exposure result in more bone loss and loss of attachment. The replaced flaps should in theory produce better aesthetics than the apical repositioned flap. In the long term however, the former tend to recede slightly whilst there is some coronal rebound in the latter, thereby producing relatively little difference between them when good plaque control is maintained. In all procedures there is loss in height of the interdental tissues, even if the labial tissue is maintained, and this can be aesthetically displeasing to some individuals. However it should also be remembered that effective non-surgical treatment can result in similar changes in tissue height and contour, and there is no guarantee of preservation of pre-existing dentogingival aesthetics. All routine periodontal treatment results in gingival shrinkage to some degree. In many cases periodontal surgery will, in reality, involve a combination of replacement, apical repositioning and resection due to the uneven pattern of disease and different anatomical constraints of the palate, tuberosities and retromolar regions. This is shown in