[Encopresis revealing myotonic dystrophy in 2 children].

PubMed

Avez-Couturier, J; Michaud, L; Cuisset, J-M; Lamblin, M-D; Dolhem, P; Turck, D; Vallée, L; Gottrand, F

2009-05-01

Gastrointestinal symptoms are very frequent in myotonic dystrophy but largely unrecognized. They can be the revealing factors of the disease. We report 2 cases of 10 and 17-year-old children with persistent encopresis starting at the age of 3 and 5 years in spite of laxative treatment. Neurological examination and anorectal manometry provided the diagnosis of myotonic dystrophy. Procainamide treatment was introduced and the digestive symptoms improved. Any child with encopresis should have complete evaluation to rule out the diagnosis of myotonic dystrophy and physicians should look for upper and/or lower gastrointestinal symptoms in every patient with myotonic dystrophy.

Analysis of MTMR1 expression and correlation with muscle pathological features in juvenile/adult onset myotonic dystrophy type 1 (DM1) and in myotonic dystrophy type 2 (DM2).

PubMed

Santoro, Massimo; Modoni, Anna; Masciullo, Marcella; Gidaro, Teresa; Broccolini, Aldobrando; Ricci, Enzo; Tonali, Pietro Attilio; Silvestri, Gabriella

2010-10-01

Among genes abnormally expressed in myotonic dystrophy type1 (DM1), the myotubularin-related 1 gene (MTMR1) was related to impaired muscle differentiation. Therefore, we analyzed MTMR1 expression in correlation with CUG-binding protein1 (CUG-BP1) and muscleblind-like1 protein (MBNL1) steady-state levels and with morphological features in muscle tissues from DM1 and myotonic dystrophy type 2 (DM2) patients. Semi-quantitative RT-PCR for MTMR1 was done on muscle biopsies and primary muscle cultures. The presence of impaired muscle fiber maturation was evaluated using immunochemistry for neural cell adhesion molecule (NCAM), Vimentin and neonatal myosin heavy chain. CUG-BP1 and MBNL1 steady-state levels were estimated by Western blot. RNA-fluorescence in situ hybridization combined with immunochemistry for CUG-BP1, MBNL1 and NCAM were performed on serial muscle sections. An aberrant splicing of MTMR1 and a significant amount of NCAM-positive myofibers were detected in DM1 and DM2 muscle biopsies; these alterations correlated with DNA repeat expansion size only in DM1. CUG-BP1 levels were increased only in DM1 muscles, while MBNL1 levels were similar among DM1, DM2 and controls. Normal and NCAM-positive myofibers displayed no differences either in the amount of ribonuclear foci and the intracellular distribution of MBNL1 and CUG-BP1. In conclusion, an aberrant MTMR1 expression and signs of altered myofiber maturation were documented in both DM1 and in DM2 muscle tissues. The more severe dysregulation of MTMR1 expression in DM1 versus DM2, along with increased CUG-BP1 levels only in DM1 tissues, suggests that the mutual antagonism between MBNL1 and CUG-BP1 on alternative splicing is more unbalanced in DM1. Copyright © 2010 Elsevier Inc. All rights reserved.

Brain gray matter structural network in myotonic dystrophy type 1.

PubMed

Sugiyama, Atsuhiko; Sone, Daichi; Sato, Noriko; Kimura, Yukio; Ota, Miho; Maikusa, Norihide; Maekawa, Tomoko; Enokizono, Mikako; Mori-Yoshimura, Madoka; Ohya, Yasushi; Kuwabara, Satoshi; Matsuda, Hiroshi

2017-01-01

This study aimed to investigate abnormalities in structural covariance network constructed from gray matter volume in myotonic dystrophy type 1 (DM1) patients by using graph theoretical analysis for further clarification of the underlying mechanisms of central nervous system involvement. Twenty-eight DM1 patients (4 childhood onset, 10 juvenile onset, 14 adult onset), excluding three cases from 31 consecutive patients who underwent magnetic resonance imaging in a certain period, and 28 age- and sex- matched healthy control subjects were included in this study. The normalized gray matter images of both groups were subjected to voxel based morphometry (VBM) and Graph Analysis Toolbox for graph theoretical analysis. VBM revealed extensive gray matter atrophy in DM1 patients, including cortical and subcortical structures. On graph theoretical analysis, there were no significant differences between DM1 and control groups in terms of the global measures of connectivity. Betweenness centrality was increased in several regions including the left fusiform gyrus, whereas it was decreased in the right striatum. The absence of significant differences between the groups in global network measurements on graph theoretical analysis is consistent with the fact that the general cognitive function is preserved in DM1 patients. In DM1 patients, increased connectivity in the left fusiform gyrus and decreased connectivity in the right striatum might be associated with impairment in face perception and theory of mind, and schizotypal-paranoid personality traits, respectively.

Increased Cancer Risks in Myotonic Dystrophy

PubMed Central

Win, Aung Ko; Perattur, Promilla G.; Pulido, Jose S.; Pulido, Christine M.; Lindor, Noralane M.

2012-01-01

Objective To estimate cancer risks for patients with myotonic dystrophy, given that increased risks for neoplasms in association with myotonic dystrophy type 1 and type 2 have been suggested in several studies but the risks of cancers have not been quantified. Patients and Methods A cohort of 307 patients with myotonic dystrophy identified from medical records of Mayo Clinic in Rochester, MN, from January 1, l993, through May 28, 2010, was retrospectively analyzed. We estimated standardized incidence ratios (SIRs) of specific cancers for patients with myotonic dystrophy compared with age- and sex-specific cancer incidences of the general population. Age-dependent cumulative risks were calculated using the Kaplan-Meier method. Results A total of 53 cancers were observed at a median age at diagnosis of 55 years. Patients with myotonic dystrophy had an increased risk of thyroid cancer (SIR, 5.54; 95% confidence interval [CI], 1.80-12.93; P=.001) and choroidal melanoma (SIR, 27.54; 95% CI, 3.34-99.49; P<.001). They may also have an increased risk of testicular cancer (SIR, 5.09; 95% CI, 0.62-18.38; P=.06) and prostate cancer (SIR, 2.21; 95% CI, 0.95-4.35; P=.05). The estimated cumulative risks at age 50 years were 1.72% (95% CI, 0.64%-4.55%) for thyroid cancer and 1.00% (95% CI, 0.25%-3.92%) for choroidal melanoma. There was no statistical evidence of an increased risk of brain, breast, colorectal, lung, renal, bladder, endometrial, or ovarian cancer; lymphoma; leukemia; or multiple myeloma. Conclusion Patients with myotonic dystrophy may have an increased risk of thyroid cancer and choroidal melanoma and, possibly, testicular and prostate cancers. PMID:22237010

Psychogenic Stuttering of Adult Onset.

ERIC Educational Resources Information Center

Mahr, Greg; Leith, William

1992-01-01

The characteristic features of psychogenic stuttering of adult onset are reviewed, and four cases of this disorder are presented. Psychogenic stuttering of adult onset is classified as a conversion reaction, and tentative criteria for this diagnosis are proposed. (Author/JDD)

[Myotonic dystrophies: clinical presentation, pathogenesis, diagnostics and therapy].

PubMed

Finsterer, Josef; Rudnik-Schöneborn, S

2015-01-01

The autosomal-dominant myotonic dystrophies dystrophia myotonica type-1 (DM1, Curschmann-Steinert disease) and dystrophia myotonica type-2 (DM2, proximal myotonic myopathy (PROMM)), are, contrary to the non-dystrophic myotonias, progressive multisystem disorders. DM1 and DM2 are the most frequent of the muscular dystrophies. In both diseases the skeletal muscle is the most severely affected organ (weakness, wasting, myotonia, myalgia). Additionally, they manifest in the eye, heart, brain, endocrine glands, gastrointestinal tract, skin, skeleton, and peripheral nerves. Phenotypes of DM1 may be classified as congenital, juvenile, classical, or late onset. DM2 is a disorder of the middle or older age and usually has a milder course compared to DM1. DM1 is due to a CTG-repeat expansion > 50 repeats in the non-coding 3' UTR of the DMPK-gene. DM2 is caused by a CCTG-repeat expansion to 75 - 11 000 repeats in intron-1 of the CNBP/ZNF9 gene. Mutant pre-mRNAs of both genes aggregate within the nucleus (nuclear foci), which sequester RNA-binding proteins and result in an abnormal protein expression via alternative splicing in downstream effector genes (toxic RNA diseases). Other mechanisms seem to play an additional pathogenetic role. Clinical severity of DM1 increases from generation to generation (anticipation). The higher the repeat expansion the more severe the DM1 phenotype. In DM2 severity of symptoms and age at onset do not correlate with the expansion size. Contrary to DM2, there is a congenital form and anticipation in DM1. © Georg Thieme Verlag KG Stuttgart · New York.

Cerebellar pathology in childhood-onset vs. adult-onset essential tremor.

PubMed

Louis, Elan D; Kuo, Sheng-Han; Tate, William J; Kelly, Geoffrey C; Faust, Phyllis L

2017-10-17

Although the incidence of ET increases with advancing age, the disease may begin at any age, including childhood. The question arises as to whether childhood-onset ET cases manifest the same sets of pathological changes in the cerebellum as those whose onset is during adult life. We quantified a broad range of postmortem features (Purkinje cell [PC] counts, PC axonal torpedoes, a host of associated axonal changes [PC axonal recurrent collateral count, PC thickened axonal profile count, PC axonal branching count], heterotopic PCs, and basket cell rating) in 60 ET cases (11 childhood-onset and 49 adult-onset) and 30 controls. Compared to controls, childhood-onset ET cases had lower PC counts, higher torpedo counts, higher heterotopic PC counts, higher basket cell plexus rating, and marginally higher PC axonal recurrent collateral counts. The median PC thickened axonal profile count and median PC axonal branching count were two to five times higher in childhood-onset ET than controls, but the differences did not reach statistical significance. Childhood-onset and adult-onset ET had similar PC counts, torpedo counts, heterotopic PC counts, basket cell plexus rating, PC axonal recurrent collateral counts, PC thickened axonal profile count and PC axonal branching count. In conclusion, we found that childhood-onset and adult-onset ET shared similar pathological changes in the cerebellum. The data suggest that pathological changes we have observed in the cerebellum in ET are a part of the pathophysiological cascade of events in both forms of the disease and that both groups seem to reach the same pathological endpoints at a similar age of death. Copyright © 2017 Elsevier B.V. All rights reserved.

Myotonic dystrophy mimicking postpolio syndrome in a polio survivor.

PubMed

Lim, Jae-Young; Kim, Kyoung-Eun; Choe, Gheeyoung

2009-02-01

We describe a 38-yr-old polio survivor with newly developed weakness from myotonic dystrophy. He suffered muscle atrophy and weakness in his legs as a result of poliomyelitis at the age of 3 yrs. After a stable interval of about 30 yrs, he felt new weakness and fatigue in his legs. Electromyography revealed generalized myotonic discharges, early recruitment, and findings of chronic denervation in his left leg. Genetic testing was consistent with myotonic dystrophy type 1. A biopsy from the right gastrocnemius revealed findings of both myotonic dystrophy and chronic denervation. This case report shows the importance of considering other uncommon conditions in the differential diagnoses of postpolio syndrome.

Adult-onset offenders: Is a tailored theory warranted?

PubMed Central

Beckley, Amber L.; Caspi, Avshalom; Harrington, Honalee; Houts, Renate M.; Mcgee, Tara Renae; Morgan, Nick; Schroeder, Felix; Ramrakha, Sandhya; Poulton, Richie; Moffitt, Terrie E.

2016-01-01

Purpose To describe official adult-onset offenders, investigate their antisocial histories and test hypotheses about their origins. Methods We defined adult-onset offenders among 931 Dunedin Study members followed to age 38, using criminal-court conviction records. Results Official adult-onset offenders were 14% of men, and 32% of convicted men, but accounted for only 15% of convictions. As anticipated by developmental theories emphasizing early-life influences on crime, adult-onset offenders’ histories of antisocial behavior spanned back to childhood. Relative to juvenile-offenders, during adolescence they had fewer delinquent peers and were more socially inhibited, which may have protected them from conviction. As anticipated by theories emphasizing the importance of situational influences on offending, adult-onset offenders, relative to non-offenders, during adulthood more often had schizophrenia, bipolar disorder, and alcohol-dependence, had weaker social bonds, anticipated fewer informal sanctions, and self-reported more offenses. Contrary to some expectations, adult-onset offenders did not have high IQ or high socioeconomic-status families protecting them from juvenile conviction. Conclusions A tailored theory for adult-onset offenders is unwarranted because few people begin crime de novo as adults. Official adult-onset offenders fall on a continuum of crime and its correlates, between official non-offenders and official juvenile-onset offenders. Existing theories can accommodate adult-onset offenders. PMID:27134318

Survey of Canadian Myotonic Dystrophy Patients' Access to Computer Technology.

PubMed

Climans, Seth A; Piechowicz, Christine; Koopman, Wilma J; Venance, Shannon L

2017-09-01

Myotonic dystrophy type 1 is an autosomal dominant condition affecting distal hand strength, energy, and cognition. Increasingly, patients and families are seeking information online. An online neuromuscular patient portal under development can help patients access resources and interact with each other regardless of location. It is unknown how individuals living with myotonic dystrophy interact with technology and whether barriers to access exist. We aimed to characterize technology use among participants with myotonic dystrophy and to determine whether there is interest in a patient portal. Surveys were mailed to 156 participants with myotonic dystrophy type 1 registered with the Canadian Neuromuscular Disease Registry. Seventy-five participants (60% female) responded; almost half were younger than 46 years. Most (84%) used the internet; almost half of the responders (47%) used social media. The complexity and cost of technology were commonly cited reasons not to use technology. The majority of responders (76%) were interested in a myotonic dystrophy patient portal. Patients in a Canada-wide registry of myotonic dystrophy have access to and use technology such as computers and mobile phones. These patients expressed interest in a portal that would provide them with an opportunity to network with others with myotonic dystrophy and to access information about the disease.

Functioning and disability in adults with myotonic dystrophy type 1.

PubMed

Kierkegaard, Marie; Harms-Ringdahl, Karin; Holmqvist, Lotta Widén; Tollbäck, Anna

2011-01-01

 To provide a comprehensive description of functioning and disability with regard to stages of disease progression in adults with myotonic dystrophy type 1 (DM1). Further to explore associations of measures of manual dexterity and of walking capacity with measures of activities of daily living (ADL) and participation in social and lifestyle activities. Seventy persons with DM1 underwent examinations, tests and answered questionnaires. Stages of disease progression were based on the muscular impairment rating scale.  Overweight, cardiac dysfunctions, respiratory restrictions, fatigue and/or low physical activity levels were found in approximately 40% of those with DM1. Over 75% had muscle impairments, and activity limitations in manual dexterity and walking. Dependence in personal and instrumental ADL was found in 16% and 39%, respectively, and participation restrictions in social and lifestyle activities in 52%. The presence of concurrent body-function impairments, activity limitations and participation restrictions was high. Significant differences were found in muscle impairment, manual dexterity, mobility, ADL and social and lifestyle activities with regard to disease progression. Cut-off values in measures of manual dexterity and walking capacity associated to functioning are proposed.  This information can be used for developing clinical practise and for health promotion for persons with DM1.

Core Clinical Phenotypes in Myotonic Dystrophies

PubMed Central

Wenninger, Stephan; Montagnese, Federica; Schoser, Benedikt

2018-01-01

Myotonic dystrophy type 1 (DM1) and type 2 (DM2) represent the most frequent multisystemic muscular dystrophies in adulthood. They are progressive, autosomal dominant diseases caused by an abnormal expansion of an unstable nucleotide repeat located in the non-coding region of their respective genes DMPK for DM1 and CNBP in DM2. Clinically, these multisystemic disorders are characterized by a high variability of muscular and extramuscular symptoms, often causing a delay in diagnosis. For both subtypes, many symptoms overlap, but some differences allow their clinical distinction. This article highlights the clinical core features of myotonic dystrophies, thus facilitating their early recognition and diagnosis. Particular attention will be given to signs and symptoms of muscular involvement, to issues related to respiratory impairment, and to the multiorgan involvement. This article is part of a Special Issue entitled “Beyond Borders: Myotonic Dystrophies—A European Perception.”

[Ocular findings in patients with Steinert myotonic dystrophy].

PubMed

Markowska, Elzbieta; Zalewska, Renata; Mariak, Zofia; Wojnar, Małgorzata

2006-01-01

The authors present one of many myotonic dystrophies: Steinert myotonic dystrophy (Steinert disease), which is a disease occuring seldom, and causing a lot of problems during the diagnostic and treatment process. Genetic factors, results of the histopathology tests, main clinical symptoms, particularly ophtalmic manifestation are described in this article.

Lower limb muscle impairment in myotonic dystrophy type 1: the need for better guidelines.

PubMed

Petitclerc, Émilie; Hébert, Luc J; Desrosiers, Johanne; Gagnon, Cynthia

2015-04-01

In myotonic dystrophy type 1 (DM1), leg muscle weakness is a major impairment. There are challenges to obtaining a clear portrait of muscle strength impairment. A systematic literature review was conducted on lower limb strength impairment in late-onset and adult phenotypes to document variables which affect strength measurement. Thirty-two articles were reviewed using the COSMIN guidelines. Only a third of the studies described a reproducible protocol. Only 2 muscle groups have documented reliability for quantitative muscle testing and only 1 total score for manual muscle testing. Variables affecting muscle strength impairment are not described in most studies. This review illustrates the variability in muscle strength assessment in relation to DM1 characteristics and the questionable validity of the results with regard to undocumented methodological properties. There is therefore a clear need to adopt a consensus on the use of a standardized muscle strength assessment protocol. © 2015 Wiley Periodicals, Inc.

Clinical Characteristics of Pediatric-Onset and Adult-Onset Multiple Sclerosis in Hispanic Americans.

PubMed

Langille, Megan M; Islam, Talat; Burnett, Margaret; Amezcua, Lilyana

2016-07-01

Multiple sclerosis can affect pediatric patients. Our aim was to compare characteristics between pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in Hispanic Americans. This was a cross-sectional analysis of 363 Hispanic American multiple scleroses cases; demographic and clinical characteristics were analyzed. A total of 110 Hispanic patients presented with multiple sclerosis before age 18 and 253 as adult multiple sclerosis. The most common presenting symptoms for both was optic neuritis. Polyfocal symptoms, seizures, and cognitive symptoms at presentation were more prevalent in pediatric-onset multiple sclerosis (P ≤ .001). Transverse myelitis was more frequent in adult-onset multiple sclerosis (P ≤ .001). Using multivariable analysis, pediatric-onset multiple sclerosis (adjusted odds ratio, 0.3OR 95% confidence interval 0.16-0.71, P = .004) and being US born (adjusted odds ratio, 0.553, 95% confidence interval 0.3-1.03, P = .006) were less likely to have severe ambulatory disability. Results suggest that pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in Hispanics have differences that could be important for treatment and prognosis. © The Author(s) 2016.

An Italian multicentre study on adult atopic dermatitis: persistent versus adult-onset disease.

PubMed

Megna, Matteo; Patruno, Cataldo; Balato, Anna; Rongioletti, Franco; Stingeni, Luca; Balato, Nicola

2017-08-01

Atopic dermatitis (AD) is a chronic, recurrent, inflammatory skin disease which predominantly affects children. However, AD may persist until adulthood (persistent AD), or directly start in adults (adult-onset AD). AD often shows a non-flexural rash distribution, and atypical morphologic variants in adults and specific diagnostic criteria are lacking. Moreover, adult AD prevalence as well as detailed data which can characterize persistent vs adult-onset subtype are scant. The aim of this study was to investigate on the main features of adult AD particularly highlighting differences between persistent vs adult-onset form. An Italian multicentre observational study was conducted between April 2015-July 2016 through a study-specific digital database. 253 adult AD patients were enrolled. Familiar history of AD was negative in 81.0%. Erythemato-desquamative pattern was the most frequent clinical presentation (74.3%). Flexural surface of upper limbs was most commonly involved (47.8%), followed by eyelid/periocular area (37.9%), hands (37.2%), and neck (32%). Hypertension (7.1%) and thyroiditis (4.3%) were the most frequent comorbidities. A subgroup analysis between persistent (59.7%) vs adult-onset AD patients (40.3%) showed significant results only regarding AD severity (severe disease was more common in persistent group, p < 0.05), itch intensity (higher in adult-onset disease), and comorbidities (hypertension was more frequent in adult-onset group, p < 0.01). Adult AD showed uncommon features such as significant association with negative AD family history and lacking of association with systemic comorbidities respect to general population. No significant differences among persistent vs adult-onset subgroup were registered except for hypertension, itch intensity, and disease severity.

Intelligence quotient profile in myotonic dystrophy, intergenerational deficit, and correlation with CTG amplification.

PubMed Central

Turnpenny, P; Clark, C; Kelly, K

1994-01-01

An abbreviated Wechsler Adult Intelligence Scale Revised (WAIS-R) was used to assess verbal and arithmetical cognitive performance in 55 subjects with myotonic dystrophy (DM), covering all grades of disease severity, and 31 controls at 50% risk of inheriting DM. Scaled scores from the assessment were converted into an intelligence quotient (IQ) estimation on each person. Significant IQ differences were found between: (1) all 55 DM subjects (mean 90.2, SD 16.1) and 31 controls (102.6, SD 9.4), with no sex differences in either group; (2) 15 affected parents (99.3, SD 12.2) and their affected children (88.1, SD 17.2), where significance was dependent on parental sex being female; and (3) 15 pairs of affected sibs (89.6, SD 13.2) and their normal sibs (100.2, SD 7.6). IQ steadily declined as (1) the age of onset of signs and symptoms decreased, and (2) the CTG expansion size increased. The correlation appeared to be more linear with age of onset. The correlation of IQ difference and CTG expansion difference in both the DM parent-child pairs and normal sib-affected sib pairs was poor, indicating that CTG expansion is not a reliable predictor of IQ either in individual persons or families. Further analysis of cognitive function in DM is required to clarify specific deficits characteristic of this patient group. PMID:8071955

[Congenital myotonic dystrophy in a Neonatal Intensive Care Unit: case series].

PubMed

Domingues, Sara; Alves Pereira, Clara; Machado, Angela; Pereira, Sandra; Machado, Leonilde; Fraga, Carla; Oliveira, Abílio; Vale, Isabel; Quelhas, Ilídio

2014-02-01

Steinert myotonic dystrophy is a multisystemic disease, autosomal dominant, with a wide spectrum of severity and clinical manifestations. The most severe form is one that manifests in the neonatal period, called congenital myotonic dystrophy. This condition is distinguished by overall hypotonia at birth and respiratory function compromise. Complications are frequent, mainly psychomotor development delay, growth failure, food difficulties and constipation. It is associated with a poor prognosis, with an overall mortality of up to 50% of severely affected children. We present five patients with congenital myotonic dystrophy in order to describe clinical manifestations, diagnosis, treatment and prognosis. Existing data in the literature on psychomotor development, complications and prognosis of survivors with congenital myotonic dystrophy are scarce. In our case studies, we have found significant chronic psychomotor limitations.

The brain in myotonic dystrophy 1 and 2: evidence for a predominant white matter disease

PubMed Central

Weber, Bernd; Schoene-Bake, Jan-Christoph; Roeske, Sandra; Mirbach, Sandra; Anspach, Christian; Schneider-Gold, Christiane; Betz, Regina C.; Helmstaedter, Christoph; Tittgemeyer, Marc; Klockgether, Thomas; Kornblum, Cornelia

2011-01-01

Myotonic dystrophy types 1 and 2 are progressive multisystemic disorders with potential brain involvement. We compared 22 myotonic dystrophy type 1 and 22 myotonic dystrophy type 2 clinically and neuropsychologically well-characterized patients and a corresponding healthy control group using structural brain magnetic resonance imaging at 3 T (T1/T2/diffusion-weighted). Voxel-based morphometry and diffusion tensor imaging with tract-based spatial statistics were applied for voxel-wise analysis of cerebral grey and white matter affection (Pcorrected < 0.05). We further examined the association of structural brain changes with clinical and neuropsychological data. White matter lesions rated visually were more prevalent and severe in myotonic dystrophy type 1 compared with controls, with frontal white matter most prominently affected in both disorders, and temporal lesions restricted to myotonic dystrophy type 1. Voxel-based morphometry analyses demonstrated extensive white matter involvement in all cerebral lobes, brainstem and corpus callosum in myotonic dystrophy types 1 and 2, while grey matter decrease (cortical areas, thalamus, putamen) was restricted to myotonic dystrophy type 1. Accordingly, we found more prominent white matter affection in myotonic dystrophy type 1 than myotonic dystrophy type 2 by diffusion tensor imaging. Association fibres throughout the whole brain, limbic system fibre tracts, the callosal body and projection fibres (e.g. internal/external capsules) were affected in myotonic dystrophy types 1 and 2. Central motor pathways were exclusively impaired in myotonic dystrophy type 1. We found mild executive and attentional deficits in our patients when neuropsychological tests were corrected for manual motor dysfunctioning. Regression analyses revealed associations of white matter affection with several clinical parameters in both disease entities, but not with neuropsychological performance. We showed that depressed mood and fatigue were

Is Adolescent-Onset First-Episode Psychosis Different from Adult Onset?

ERIC Educational Resources Information Center

Ballageer, Trevor; Malla, Ashok; Manchanda, Rahul; Takhar, Jatinder; Haricharan, Raj

2005-01-01

Objective: To examine whether first-episode psychosis patients with onset during adolescence (ages 15-18) differ significantly from those with young-adult onset (ages 19-30). Method: Consecutive patients presenting with first-episode psychosis (N = 242) were assessed for demographic and illness characteristics such as duration of untreated…

Epiretinal membrane: a treatable cause of visual disability in myotonic dystrophy type 1.

PubMed

Kersten, Hannah M; Roxburgh, Richard H; Child, Nicholas; Polkinghorne, Philip J; Frampton, Chris; Danesh-Meyer, Helen V

2014-01-01

A wide range of ocular abnormalities have been documented to occur in patients with myotonic dystrophy type 1. The objectives of this study were to investigate the macular and optic nerve morphology using optical coherence tomography in patients with myotonic dystrophy type 1. A total of 30 myotonic dystrophy type 1 patients and 28 controls were recruited for participation. All participants underwent a thorough ophthalmologic examination, including spectral-domain optical coherence tomography of the macula and retinal nerve fibre layer. Images were reviewed by a retinal specialist ophthalmologist, masked to the diagnosis of the participants. Average macular thickness was significantly greater in the myotonic dystrophy group compared to controls [327.3 μm vs. 308.5 μm (p < 0.001)]. Macular thickness was significantly greater (p < 0.005) in five of the nine macular regions. The increase in macular thickness was due to the increased prevalence of epiretinal membranes in the myotonic dystrophy patient group (p = 0.0002): 48.2 % of myotonic dystrophy patient eyes had evidence of epiretinal membrane, compared with 12.5 % of control eyes. Examination revealed that 56.7 % of myotonic dystrophy patients had an epiretinal membrane in at least one eye. Visual acuity was reduced due to the presence of epiretinal membrane in six patient eyes and none of the control eyes. The presence of an epiretinal membrane was significantly correlated with increasing age in the patient group. We report an increased prevalence of epiretinal membrane in the myotonic dystrophy type 1 group. This may be a previously under-recognised form of visual impairment in this group. Epiretinal membranes can be treated surgically. We suggest that, in addition to a comprehensive clinical examination, optical coherence tomography examination is implemented as part of an ophthalmological assessment for the myotonic dystrophy type 1 patient with reduced visual acuity.

X-linked adult-onset adrenoleukodystrophy: Psychiatric and neurological manifestations

PubMed Central

Shamim, Daniah; Alleyne, Karen

2017-01-01

Adult-onset adrenoleukodystrophy is a rare x-linked inborn error of metabolism occurring predominantly in males with onset in early 30s. Here, we report a 34-year-old male with first signs of disease in early 20s manifesting as a pure psychiatric disorder. Prior to onset of neurological symptoms, this patient demonstrated a schizophrenia and bipolar-like presentation. The disease progressed over the next 10–13 years and his memory and motor problems became evident around the age of 33 years. Subsequently, diagnostic testing showed the typical magnetic resonance imaging and lab findings for adult-onset adrenoleukodystrophy. This case highlights adult-onset adrenoleukodystrophy which may present as a pure psychiatric disturbance in early adulthood and briefly discusses the prolonged time between the onset of psychiatric symptoms and the onset of neurological disease. PMID:29201369

X-linked adult-onset adrenoleukodystrophy: Psychiatric and neurological manifestations.

PubMed

Shamim, Daniah; Alleyne, Karen

2017-01-01

Adult-onset adrenoleukodystrophy is a rare x-linked inborn error of metabolism occurring predominantly in males with onset in early 30s. Here, we report a 34-year-old male with first signs of disease in early 20s manifesting as a pure psychiatric disorder. Prior to onset of neurological symptoms, this patient demonstrated a schizophrenia and bipolar-like presentation. The disease progressed over the next 10-13 years and his memory and motor problems became evident around the age of 33 years. Subsequently, diagnostic testing showed the typical magnetic resonance imaging and lab findings for adult-onset adrenoleukodystrophy. This case highlights adult-onset adrenoleukodystrophy which may present as a pure psychiatric disturbance in early adulthood and briefly discusses the prolonged time between the onset of psychiatric symptoms and the onset of neurological disease.

Increased autophagy and apoptosis contribute to muscle atrophy in a myotonic dystrophy type 1 Drosophila model

PubMed Central

Bargiela, Ariadna; Cerro-Herreros, Estefanía; Fernandez-Costa, Juan M.; Vilchez, Juan J.; Llamusi, Beatriz; Artero, Ruben

2015-01-01

ABSTRACT Muscle mass wasting is one of the most debilitating symptoms of myotonic dystrophy type 1 (DM1) disease, ultimately leading to immobility, respiratory defects, dysarthria, dysphagia and death in advanced stages of the disease. In order to study the molecular mechanisms leading to the degenerative loss of adult muscle tissue in DM1, we generated an inducible Drosophila model of expanded CTG trinucleotide repeat toxicity that resembles an adult-onset form of the disease. Heat-shock induced expression of 480 CUG repeats in adult flies resulted in a reduction in the area of the indirect flight muscles. In these model flies, reduction of muscle area was concomitant with increased apoptosis and autophagy. Inhibition of apoptosis or autophagy mediated by the overexpression of DIAP1, mTOR (also known as Tor) or muscleblind, or by RNA interference (RNAi)-mediated silencing of autophagy regulatory genes, achieved a rescue of the muscle-loss phenotype. In fact, mTOR overexpression rescued muscle size to a size comparable to that in control flies. These results were validated in skeletal muscle biopsies from DM1 patients in which we found downregulated autophagy and apoptosis repressor genes, and also in DM1 myoblasts where we found increased autophagy. These findings provide new insights into the signaling pathways involved in DM1 disease pathogenesis. PMID:26092529

Increased autophagy and apoptosis contribute to muscle atrophy in a myotonic dystrophy type 1 Drosophila model.

PubMed

Bargiela, Ariadna; Cerro-Herreros, Estefanía; Fernandez-Costa, Juan M; Vilchez, Juan J; Llamusi, Beatriz; Artero, Ruben

2015-07-01

Muscle mass wasting is one of the most debilitating symptoms of myotonic dystrophy type 1 (DM1) disease, ultimately leading to immobility, respiratory defects, dysarthria, dysphagia and death in advanced stages of the disease. In order to study the molecular mechanisms leading to the degenerative loss of adult muscle tissue in DM1, we generated an inducible Drosophila model of expanded CTG trinucleotide repeat toxicity that resembles an adult-onset form of the disease. Heat-shock induced expression of 480 CUG repeats in adult flies resulted in a reduction in the area of the indirect flight muscles. In these model flies, reduction of muscle area was concomitant with increased apoptosis and autophagy. Inhibition of apoptosis or autophagy mediated by the overexpression of DIAP1, mTOR (also known as Tor) or muscleblind, or by RNA interference (RNAi)-mediated silencing of autophagy regulatory genes, achieved a rescue of the muscle-loss phenotype. In fact, mTOR overexpression rescued muscle size to a size comparable to that in control flies. These results were validated in skeletal muscle biopsies from DM1 patients in which we found downregulated autophagy and apoptosis repressor genes, and also in DM1 myoblasts where we found increased autophagy. These findings provide new insights into the signaling pathways involved in DM1 disease pathogenesis. © 2015. Published by The Company of Biologists Ltd.

Unravelling the myotonic dystrophy type 1 clinical spectrum: A systematic registry-based study with implications for disease classification.

PubMed

De Antonio, M; Dogan, C; Hamroun, D; Mati, M; Zerrouki, S; Eymard, B; Katsahian, S; Bassez, G

2016-10-01

The broad clinical spectrum of myotonic dystrophy type 1 (DM1) creates particular challenges for both medical care and design of clinical trials. Clinical onset spans a continuum from birth to late adulthood, with symptoms that are highly variable in both severity and nature of the affected organ systems. In the literature, this complex phenotype is divided into three grades (mild, classic, and severe) and four or five main clinical categories (congenital, infantile/juvenile, adult-onset and late-onset forms), according to symptom severity and age of onset, respectively. However, these classifications are still under discussion with no consensus thus far. While some specific clinical features have been primarily reported in some forms of the disease, there are no clear distinctions. As a consequence, no modifications in the management of healthcare or the design of clinical studies have been proposed based on the clinical form of DM1. The present study has used the DM-Scope registry to assess, in a large cohort of DM1 patients, the robustness of a classification divided into five clinical forms. Our main aim was to describe the disease spectrum and investigate features of each clinical form. The five subtypes were compared by distribution of CTG expansion size, and the occurrence and onset of the main symptoms of DM1. Analyses validated the relevance of a five-grade model for DM1 classification. Patients were classified as: congenital (n=93, 4.5%); infantile (n=303, 14.8%); juvenile (n=628, 30.7%); adult (n=694, 34.0%); and late-onset (n=326, 15.9%). Our data show that the assumption of a continuum from congenital to the late-onset form is valid, and also highlights disease features specific to individual clinical forms of DM1 in terms of symptom occurrence and chronology throughout the disease course. These results support the use of the five-grade model for disease classification, and the distinct clinical profiles suggest that age of onset and clinical form may

Juvenile and adult-onset psychogenic non-epileptic seizures.

PubMed

Asadi-Pooya, Ali A; Emami, Mehrdad

2013-09-01

Psychogenic non-epileptic seizures (PNES) tend to begin in adolescence and young adulthood, although the seizures can occur in a wide range of ages. In the current study, we investigated the age of onset in patients with PNES and tried to determine the correlation between the age of onset and the demographic and clinical characteristics and factors potentially predisposing to PNES. In this cross-sectional study, all patients with a clinical diagnosis of PNES were recruited at the outpatient epilepsy clinic at Shiraz University of Medical Sciences from 2008 to 2012. We dichotomized the patients into two groups; those with age of onset below 18 years (juvenile), and those with age of onset at 18-55 years (adult-onset). We studied the demographic and clinical characteristics and factors potentially predisposing to PNES between these two groups. Statistical analyses were performed using Chi square and Fisher's Exact tests and Mann-Whitney U test. Fifty-seven patients with juvenile and 129 people with adult-onset PNES were studied. Demographic characteristics of these two groups were not different significantly. Seizure characteristics and semiology in these two groups were not significantly different either. However, factors potentially predisposing to PNES were significantly different between these two groups. History of being abused, academic failure, epilepsy or family history of epilepsy were more frequently observed in juvenile PNES, while medical comorbidities were more frequent among patients with adult-onset PNES. Age of onset of PNES is not correlated with the clinical manifestations; however, factors potentially predisposing to PNES are significantly different in patients with juvenile compared to those with adult-onset PNES. Copyright © 2013 Elsevier B.V. All rights reserved.

Association between mental disorders and subsequent adult onset asthma

PubMed Central

Alonso, Jordi; de Jonge, Peter; Lim, Carmen C. W.; Aguilar-Gaxiola, Sergio; Bruffaerts, Ronny; Caldas-de-Almeida, Jose Miguel; Liu, Zhaorui; O'Neill, Siobhan; Stein, Dan J.; Viana, Maria Carmen; Al-Hamzawi, Ali Obaid; Angermeyer, Matthias C.; Borges, Guilherme; Ciutan, Marius; de Girolamo, Giovanni; Fiestas, Fabian; Haro, Josep Maria; Hu, Chiyi; Kessler, Ronald C.; Lépine, Jean Pierre; Levinson, Daphna; Nakamura, Yosikazu; Posada-Villa, Jose; Wojtyniak, Bogdan J; Scott, Kate M.

2016-01-01

Background and objectives Associations between asthma and anxiety and mood disorders are well established, but little is known about their temporal sequence. We examined associations between a wide range of DSM-IV mental disorders with adult onset of asthma and whether observed associations remain after mental comorbidity adjustments. Methods During face-to-face household surveys in community-dwelling adults (n = 52,095) of 19 countries, the WHO Composite International Diagnostic Interview retrospectively assessed lifetime prevalence and age at onset of 16 DSM-IV mental disorders. Asthma was assessed by self-report of physician’s diagnosis together with age of onset. Survival analyses estimated associations between first onset of mental disorders and subsequent adult onset asthma, without and with comorbidity adjustment. Results 1,860 adult onset (21 years+) asthma cases were identified, representing a total of 2,096,486 person-years of follow up. After adjustment for comorbid mental disorders several mental disorders were associated with subsequent adult asthma onset: bipolar (OR=1.8; 95%CI 1.3–2.4), panic (OR=1.4; 95%CI 1.0–2.0), generalized anxiety (OR=1.3; 95%CI 1.1–1.7), specific phobia (OR=1.4; 95%CI 1.2–1.6); post-traumatic stress (OR=1.5; 95%CI 1.1–2.0); binge eating (OR=1.9; 95%CI 1.2–2.9) and alcohol abuse (OR=1.5; 95%CI 1.2–2.0). Mental comorbidity linearly increased the association with adult asthma. The association with subsequent asthma was stronger for mental disorders with an early onset (before age 21). Conclusions A wide range of temporally prior mental disorders are significantly associated with subsequent onset of asthma in adulthood. The extent to which asthma can be avoided or improved among those with early mental disorders deserves study. PMID:25263276

Association between mental disorders and subsequent adult onset asthma.

PubMed

Alonso, Jordi; de Jonge, Peter; Lim, Carmen C W; Aguilar-Gaxiola, Sergio; Bruffaerts, Ronny; Caldas-de-Almeida, Jose Miguel; Liu, Zhaorui; O'Neill, Siobhan; Stein, Dan J; Viana, Maria Carmen; Al-Hamzawi, Ali Obaid; Angermeyer, Matthias C; Borges, Guilherme; Ciutan, Marius; de Girolamo, Giovanni; Fiestas, Fabian; Haro, Josep Maria; Hu, Chiyi; Kessler, Ronald C; Lépine, Jean Pierre; Levinson, Daphna; Nakamura, Yosikazu; Posada-Villa, Jose; Wojtyniak, Bogdan J; Scott, Kate M

2014-12-01

Associations between asthma and anxiety and mood disorders are well established, but little is known about their temporal sequence. We examined associations between a wide range of DSM-IV mental disorders with adult onset of asthma and whether observed associations remain after mental comorbidity adjustments. During face-to-face household surveys in community-dwelling adults (n = 52,095) of 19 countries, the WHO Composite International Diagnostic Interview retrospectively assessed lifetime prevalence and age at onset of 16 DSM-IV mental disorders. Asthma was assessed by self-report of physician's diagnosis together with age of onset. Survival analyses estimated associations between first onset of mental disorders and subsequent adult onset asthma, without and with comorbidity adjustment. 1860 adult onset (21 years+) asthma cases were identified, representing a total of 2,096,486 person-years of follow up. After adjustment for comorbid mental disorders several mental disorders were associated with subsequent adult asthma onset: bipolar (OR = 1.8; 95%CI 1.3-2.5), panic (OR = 1.4; 95%CI 1.0-2.0), generalized anxiety (OR = 1.3; 95%CI 1.1-1.7), specific phobia (OR = 1.3; 95%CI 1.1-1.6); post-traumatic stress (OR = 1.5; 95%CI 1.1-1.9); binge eating (OR = 1.8; 95%CI 1.2-2.9) and alcohol abuse (OR = 1.5; 95%CI 1.1-2.0). Mental comorbidity linearly increased the association with adult asthma. The association with subsequent asthma was stronger for mental disorders with an early onset (before age 21). A wide range of temporally prior mental disorders are significantly associated with subsequent onset of asthma in adulthood. The extent to which asthma can be avoided or improved among those with early mental disorders deserves study. Copyright © 2014 Elsevier Ltd. All rights reserved.

Alcohol-Induced Developmental Origins of Adult-Onset Diseases

PubMed Central

Lunde, Emilie R.; Washburn, Shannon E.; Golding, Michael C.; Bake, Shameena; Miranda, Rajesh C.; Ramadoss, Jayanth

2016-01-01

Fetal alcohol exposure may impair growth, development, and function of multiple organ systems, and is encompassed by the term Fetal Alcohol Spectrum Disorders (FASD). Research has so far focused on the mechanisms, prevention, and diagnosis of FASD, while the risk for adult-onset chronic diseases in individuals exposed to alcohol in utero is not well explored. David Barker’s hypothesis on Developmental Origins of Health and Disease (DOHaD) suggests that insults to the milieu of the developing fetus program it for adult-development of chronic diseases. In the 25 years since the introduction of this hypothesis, epidemiological and animal model studies have made significant advancements in identifying in utero developmental origins of chronic adult-onset diseases affecting cardiovascular, endocrine, musculoskeletal, and psycho-behavioral systems. Teratogen exposure is an established programming agent for adult diseases, and recent studies suggest that prenatal alcohol exposure correlates with adult-onset of neuro-behavioral deficits, cardiovascular disease, endocrine dysfunction, nutrient homeostasis instability, warranting additional investigation of alcohol-induced DOHaD, as well as patient follow-up well into adulthood for affected individuals. In utero epigenetic alterations during critical periods of methylation is a key potential mechanism for programming and susceptibility of adult-onset chronic diseases, with imprinted genes affecting metabolism being critical targets. Additional studies in epidemiology, phenotypic characterization in response to timing, dose and duration of exposure, as well as elucidation of mechanisms underlying FASD-DOHaD inter-relation are thus needed to clinically define chronic disease associated with prenatal alcohol exposure. These studies are critical to establish interventional strategies that decrease incidence of these adult-onset diseases and promote healthier aging among individuals affected with FASD. PMID:27254466

Reliability and feasibility of the six minute walk test in subjects with myotonic dystrophy.

PubMed

Kierkegaard, Marie; Tollbäck, Anna

2007-12-01

The objective was to describe test-retest reliability and feasibility of the six minute walk test in adult subjects with myotonic dystrophy type 1. Twelve subjects (28-68 years, mean 44) performed three six minute walk tests on two occasions, one week apart. Relative reliability was high (ICC(2.1)=0.99) and absolute reliability values were low (standard error of measurement 12 m, repeatability 33 m). Feasibility was investigated in a sample of 64 subjects (19-70 years, mean 43). Fifty-two subjects were able to perform two tests on the same day. Subjects with severe proximal weakness had difficulties performing repeated tests. A practice trial followed by a second test on the same day can be recommended for most subjects, and the best test should be used for evaluations. In conclusion, even though the study sample was small, the present study indicates that the six minute walk test is reliable and feasible in subjects with myotonic dystrophy type 1.

Longitudinal in vivo muscle function analysis of the DMSXL mouse model of myotonic dystrophy type 1.

PubMed

Decostre, Valérie; Vignaud, Alban; Matot, Béatrice; Huguet, Aline; Ledoux, Isabelle; Bertil, Emilie; Gjata, Bernard; Carlier, Pierre G; Gourdon, Geneviève; Hogrel, Jean-Yves

2013-12-01

Myotonic dystrophy is the most common adult muscle dystrophy. In view of emerging therapies, which use animal models as a proof of principle, the development of reliable outcome measures for in vivo longitudinal study of mouse skeletal muscle function is becoming crucial. To satisfy this need, we have developed a device to measure ankle dorsi- and plantarflexion torque in rodents. We present an in vivo 8-month longitudinal study of the contractile properties of the skeletal muscles of the DMSXL mouse model of myotonic dystrophy type 1. Between 4 and 12 months of age, we observed a reduction in muscle strength in the ankle dorsi- and plantarflexors of DMSXL compared to control mice although the strength per muscle cross-section was normal. Mild steady myotonia but no abnormal muscle fatigue was also observed in the DMSXL mice. Magnetic resonance imaging and histological analysis performed at the end of the study showed respectively reduced muscle cross-section area and smaller muscle fibre diameter in DMSXL mice. In conclusion, our study demonstrates the feasibility of carrying out longitudinal in vivo studies of muscle function over several months in a mouse model of myotonic dystrophy confirming the feasibility of this method to test preclinical therapeutics. Copyright © 2013 Elsevier B.V. All rights reserved.

Two Sides of the Same Coin: Pediatric-Onset and Adult-Onset Common Variable Immune Deficiency.

PubMed

Sanchez, Lauren A; Maggadottir, Solrun Melkorka; Pantell, Matthew S; Lugar, Patricia; Rundles, Charlotte Cunningham; Sullivan, Kathleen E

2017-08-01

Common variable immunodeficiency (CVID) is a complex, heterogeneous immunodeficiency characterized by hypogammaglobulinemia, recurrent infections, and poor antibody response to vaccination. While antibiotics and immunoglobulin prophylaxis have significantly reduced infectious complications, non-infectious complications of autoimmunity, inflammatory lung disease, enteropathy, and malignancy remain of great concern. Previous studies have suggested that CVID patients diagnosed in childhood are more severely affected by these complications than adults diagnosed later in life. We sought to discern whether the rates of various infectious and non-infectious conditions differed between pediatric-diagnosed (ages 17 or younger) versus adult-diagnosed CVID (ages 18 or older). Using the United States Immunodeficiency Network (USIDNET) database, we performed a retrospective analysis of 457 children and adults with CVID, stratified by age at diagnosis. Chi-squared testing was used to compare pediatric versus adult groups. After correcting for multiple comparisons, we identified few statistically significant differences (p ≤ 0.0004) between pediatric and adult groups. Pediatric-onset CVID patients had more frequent diagnoses of otitis media, developmental delay, and failure to thrive compared with adult-onset CVID patients. Adult CVID patients were more frequently diagnosed with bronchitis, arthritis, depression, and fatigue. Diagnoses of autoimmunity, lymphoma, and other malignancies were higher in adults but not to a significant degree. Serum immunoglobulins (IgG, IgA, and IgM) and lymphocyte subsets did not differ significantly between the two groups. When complications of infections and co-morbid conditions were viewed categorically, there were few differences between pediatric-onset and adult-onset CVID patients. These results suggest that pediatric CVID is not a distinct phenotype. Major features were comparable across the groups. This study underscores the need for

Alcohol-Induced Developmental Origins of Adult-Onset Diseases.

PubMed

Lunde, Emilie R; Washburn, Shannon E; Golding, Michael C; Bake, Shameena; Miranda, Rajesh C; Ramadoss, Jayanth

2016-07-01

Fetal alcohol exposure may impair growth, development, and function of multiple organ systems and is encompassed by the term fetal alcohol spectrum disorders (FASD). Research has so far focused on the mechanisms, prevention, and diagnosis of FASD, while the risk for adult-onset chronic diseases in individuals exposed to alcohol in utero is not well explored. David Barker's hypothesis on Developmental Origins of Health and Disease (DOHaD) suggests that insults to the milieu of the developing fetus program it for adult development of chronic diseases. In the 25 years since the introduction of this hypothesis, epidemiological and animal model studies have made significant advancements in identifying in utero developmental origins of chronic adult-onset diseases affecting cardiovascular, endocrine, musculoskeletal, and psychobehavioral systems. Teratogen exposure is an established programming agent for adult diseases, and recent studies suggest that prenatal alcohol exposure correlates with adult onset of neurobehavioral deficits, cardiovascular disease, endocrine dysfunction, and nutrient homeostasis instability, warranting additional investigation of alcohol-induced DOHaD, as well as patient follow-up well into adulthood for affected individuals. In utero epigenetic alterations during critical periods of methylation are a key potential mechanism for programming and susceptibility of adult-onset chronic diseases, with imprinted genes affecting metabolism being critical targets. Additional studies in epidemiology, phenotypic characterization in response to timing, dose, and duration of exposure, as well as elucidation of mechanisms underlying FASD-DOHaD inter relation, are thus needed to clinically define chronic disease associated with prenatal alcohol exposure. These studies are critical to establish interventional strategies that decrease incidence of these adult-onset diseases and promote healthier aging among individuals affected with FASD. Copyright © 2016 by

Juvenile-Onset OCD: Clinical Features in Children, Adolescents and Adults

PubMed Central

Mancebo, Maria C.; Garcia, Abbe M.; Pinto, Anthony; Freeman, Jennifer B.; Przeworski, Amy; Stout, Robert; Kane, Joshua S.; Eisen, Jane L.; Rasmussen, Steven A.

2009-01-01

Objective To examine clinical correlates of juvenile-onset OCD across the lifespan. Method Intake data collected from 257 consecutive participants with a juvenile-onset of OCD (20 children, 44 adolescents, and 193 adults) in a naturalistic study of the clinical course of OCD were examined. Participants and parents of juvenile participants completed a structured diagnostic interview, rater-administered severity measures, and self-report questionnaires. Results Children and adolescents (i.e. juveniles) shared similar features with the exception of age at onset and OCD symptom expression. Clinically meaningful differences between juvenile and adult participants were also found. Compared to adults, juveniles were more likely to be male, recall an earlier age at OCD onset, and have different lifetime comorbidity patterns. Conclusion Juvenile-onset OCD symptom expression is remarkably similar across the lifespan. However, findings also suggest clinically meaningful differences between juveniles and adults. Future work using a prospective design will improve our understanding of course patterns of juvenile-onset OCD. Significant Outcomes •Children were less likely than either adolescent or adults to report aggressive obsessions and mental rituals. •Males were overrepresented in the juvenile sample but gender was equally distributed in the adult sample •Compared to lifetime comorbidity patterns of adults, juveniles showed elevated rates of ADHD and lower rates of mood, substance use and eating disorders Limitations •The cross-sectional design with retrospective recall regarding course prior to study entry limits conclusions about the course of OCD. •The adult sample is limited to adults whose symptoms persisted into adulthood and therefore results cannot be generalized to all individuals with a juvenile-onset. •The small number of very young children (under age 10) may have limited power to detect differences among children and adolescents. PMID:18699949

Is adolescent-onset first-episode psychosis different from adult onset?

PubMed

Ballageer, Trevor; Malla, Ashok; Manchanda, Rahul; Takhar, Jatinder; Haricharan, Raj

2005-08-01

To examine whether first-episode psychosis patients with onset during adolescence (ages 15-18) differ significantly from those with young-adult onset (ages 19-30). Consecutive patients presenting with first-episode psychosis (N = 242) were assessed for demographic and illness characteristics such as duration of untreated psychosis, diagnosis, length of prodromal period, premorbid adjustment, level of psychotic, negative, depressive, anxiety, and extrapyramidal symptoms, and alcohol and drug use. Eighty-two patients (40.8%) had an onset of psychosis during adolescence (ages 15-18) and 119 (59.2%) during young adulthood (ages 19-30). The adolescent-onset group experienced longer delays in treatment of psychosis (duration of untreated psychosis) (p < .02), showed modestly worse premorbid functioning during late adolescence (p < .05), and were more likely to present with bizarre behavior (p < .01) and primary negative symptoms (p < .01). Patients with adolescent onset of psychosis are more likely to present with clinical characteristics that portend a poorer outcome and may require a different approach to early identification and treatment.

Hereditary myopathies with early respiratory insufficiency in adults.

PubMed

Naddaf, Elie; Milone, Margherita

2017-11-01

Hereditary myopathies with early respiratory insufficiency as a predominant feature of the clinical phenotype are uncommon and underestimated in adults. We reviewed the clinical and laboratory data of patients with hereditary myopathies who demonstrated early respiratory insufficiency before the need for ambulatory assistance. Only patients with disease-causing mutations or a specific histopathological diagnosis were included. Patients with cardiomyopathy were excluded. We identified 22 patients; half had isolated respiratory symptoms at onset. The diagnosis of the myopathy was often delayed, resulting in delayed ventilatory support. The most common myopathies were adult-onset Pompe disease, myofibrillar myopathy, multi-minicore disease, and myotonic dystrophy type 1. Single cases of laminopathy, MELAS (mitochondrial encephalomyopathy with lactic acidosis and strokelike events), centronuclear myopathy, and cytoplasmic body myopathy were identified. We highlighted the most common hereditary myopathies associated with early respiratory insufficiency as the predominant clinical feature, and underscored the importance of a timely diagnosis for patient care. Muscle Nerve 56: 881-886, 2017. © 2017 Wiley Periodicals, Inc.

Antimyotonic therapy with tocainide under ECG control in the myotonic dystrophy of Curschmann-Steinert.

PubMed

Mielke, U; Haass, A; Sen, S; Schmidt, W

1985-01-01

Ten patients suffering from advanced myotonic dystrophy with severe myotonic symptoms were treated with 800-1200 mg/day of the anti-arrhythmic drug tocainide (Xylotocan). All patients reported a marked subjective improvement of myotonia, which was confirmed by objective tests. Except for a slight QT-prolongation in one patient, the ECG was not significantly altered by the treatment. Twenty-four-hour ECG after treatment disclosed that pre-existing ventricular arrhythmia disappeared in three cases. The occurrence of complex ventricular arrhythmia in two patients under treatment was not necessarily due to specific effects of the drug but might be explained by the high spontaneous variability of rhythm disorders. In these patients suffering from myotonic dystrophy with typical cardiomyopathy no deleterious effects of the drug were observed, especially no cardiac arrhythmias which would have necessitated interruption of treatment. Therefore, the authors recommend symptomatic therapy with tocainide for myotonia and paramyotonia congenita, as well as in myotonic dystrophy patients suffering from marked myotonic stiffness. ECG and 24-h ECG should be carefully recorded as necessary in any treatment with anti-arrhythmic drugs.

Rest tremor in idiopathic adult-onset dystonia.

PubMed

Gigante, A F; Berardelli, A; Defazio, G

2016-05-01

Tremor in dystonia has been described as a postural or kinetic abnormality. In recent series, however, patients with idiopathic adult-onset dystonia also displayed rest tremor. The frequency and distribution of rest tremor were studied in a cohort of 173 consecutive Italian patients affected by various forms of idiopathic adult-onset dystonia attending our movement disorder clinic over 8 months. Examination revealed tremor in 59/173 patients (34%): 12 patients had head tremor, 34 patients had arm tremor, whilst 13 patients presented tremor in both sites. Head tremor was postural in all patients, whereas arm tremor was postural/kinetic in 28 patients, only at rest in one and both postural/kinetic and at rest in 18 patients. Patients with tremor were more likely to have segmental/multifocal dystonia. Patients who had rest tremor (either alone or associated with action tremor) had a higher age at dystonia onset and a greater frequency of dystonic arm involvement than patients with action tremor alone or without tremor. Both action and rest tremor are part of the tremor spectrum of adult-onset dystonia and are more frequently encountered in segmental/multifocal dystonia. The higher age at dystonia onset and the greater frequency of arm dystonia in patients with rest tremor may have pathophysiological implications and may account, at least in part, for the previous lack of identification of rest tremor as one possible type of tremor present in dystonia. © 2016 EAN.

Childhood Onset Schizophrenia: Cortical Brain Abnormalities as Young Adults

ERIC Educational Resources Information Center

Greenstein, Deanna; Lerch, Jason; Shaw, Philip; Clasen, Liv; Giedd, Jay; Gochman, Peter; Rapoport, Judith; Gogtay, Nitin

2006-01-01

Background: Childhood onset schizophrenia (COS) is a rare but severe form of the adult onset disorder. While structural brain imaging studies show robust, widespread, and progressive gray matter loss in COS during adolescence, there have been no longitudinal studies of sufficient duration to examine comparability with the more common adult onset…

Brain MRI abnormalities in the adult form of myotonic dystrophy type 1: A longitudinal case series study.

PubMed

Conforti, Renata; de Cristofaro, Mario; Cristofano, Adriana; Brogna, Barbara; Sardaro, Angela; Tedeschi, Gioacchino; Cirillo, Sossio; Di Costanzo, Alfonso

2016-02-01

This study aimed to verify whether brain abnormalities, previously described in patients with myotonic dystrophy type 1 (DM1) by magnetic resonance imaging (MRI), progressed over time and, if so, to characterize their progression. Thirteen DM1 patients, who had at least two MRI examinations, were retrospectively evaluated and included in the study. The mean duration (± standard deviation) of follow-up was 13.4 (±3.8) years, over a range of 7-20 years. White matter lesions (WMLs) were rated by semi-quantitative method, the signal intensity of white matter poster-superior to trigones (WMPST) by reference to standard images and brain atrophy by ventricular/brain ratio (VBR). At the end of MRI follow-up, the scores relative to lobar, temporal and periventricular WMLs, to WMPST signal intensity and to VBR were significantly increased compared to baseline, and MRI changes were more evident in some families than in others. No correlation was found between the MRI changes and age, onset, disease duration, muscular involvement, CTG repetition and follow-up duration. These results demonstrated that white matter involvement and brain atrophy were progressive in DM1 and suggested that progression rate varied from patient to patient, regardless of age, disease duration and genetic defect. © The Author(s) 2016.

A 12-year prognosis of adult-onset asthma: Seinäjoki Adult Asthma Study.

PubMed

Tuomisto, Leena E; Ilmarinen, Pinja; Niemelä, Onni; Haanpää, Jussi; Kankaanranta, Terhi; Kankaanranta, Hannu

2016-08-01

Long-term prognosis of adult-onset asthma is poorly known. To evaluate 12-year prognosis of adult-onset asthma and the factors associated with disease prognosis. Seinäjoki Adult-onset Asthma Study (SAAS) is a 12-year real-life single-center follow-up study of new-onset asthma diagnosed at adult age and treated in primary and specialized care. Remission was defined by no symptoms and no asthma medication use for 6 months. Asthma control was evaluated according to Global Initiative for Asthma 2010. Factors associated with current asthma control were analyzed by multinomial multivariate logistic regression. A total of 203 patients (79% of the baseline population) were followed for 12 years. Remission occurred in 6 (3%) patients. In 34% asthma was controlled, in 36% it was partially controlled and in 30% uncontrolled. Uncontrolled asthma was predicted by elevated body-mass index at baseline, smoking (pack-years) and current allergic or persistent rhinitis. Elevated blood eosinophils and good lung function (FEV1) at baseline protected from uncontrolled asthma. In contrast, gender, age at the onset or baseline symptoms (Airways Questionnaire 20) were not significant predictors of uncontrolled disease. During a 12-year follow-up, remission of adult-onset asthma was rare occurring in only 3% of patients. The majority of patients (66%) presented either with uncontrolled or partially controlled asthma. This study is registered at ClinicalTrials.gov with identifier number NCT02733016. Copyright © 2016 Elsevier Ltd. All rights reserved.

Peripheral neuropathy in patients with myotonic dystrophy type 2.

PubMed

Leonardis, L

2017-05-01

Myotonic dystrophy type 2 (dystrophia myotonica type 2-DM2) is an autosomal dominant multi-organ disorder. The involvement of the peripheral nervous system was found in 25%-45% of patients with myotonic dystrophy type 1, although limited data are available concerning polyneuropathy in patients with DM2, which was the aim of this study with a thorough presentation of the cases with peripheral neuropathy. Patients with genetically confirmed DM2 underwent motor nerve conduction studies of the median, ulnar, tibial and fibular nerves and sensory nerve conduction studies of the median (second finger), ulnar (fifth finger), radial (forearm) and sural nerves. Seventeen adult patients with DM2 participated in the study. Fifty-three percent (9/17) of our patients had abnormality of one or more attributes (latency, amplitude or conduction velocity) in two or more separate nerves. Four types of neuropathies were found: (i) predominantly axonal motor and sensory polyneuropathy, (ii) motor polyneuropathy, (iii) predominantly demyelinating motor and sensory polyneuropathy and (iv) mutilating polyneuropathy with ulcers. The most common forms are axonal motor and sensory polyneuropathy (29%) and motor neuropathy (18% of all examined patients). No correlations were found between the presence of neuropathy and age, CCTG repeats, blood glucose or HbA1C. Peripheral neuropathy is common in patients with DM2 and presents one of the multisystemic manifestations of DM2. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Late-onset ADHD in adults: milder, but still dysfunctional.

PubMed

Karam, Rafael G; Bau, Claiton H D; Salgado, Carlos A I; Kalil, Katiane L S; Victor, Marcelo M; Sousa, Nyvia O; Vitola, Eduardo S; Picon, Felipe A; Zeni, Gregory D; Rohde, Luis A; Belmonte-de-Abreu, Paulo; Grevet, Eugenio H

2009-04-01

The requirement in classificatory systems that some impairment from attention-deficit/hyperactivity disorder (ADHD) symptoms starts before 7 years of age (age of onset of impairment criteria - AOC) has been harshly criticized. Although there is evidence that late-onset ADHD is a valid diagnosis, little is known about the role of age of onset of impairment on the clinical profile of adult patients. The diagnoses of 349 adults with ADHD followed DSM-IV criteria. ADHD and oppositional defiant disorder (ODD) were evaluated with the K-SADS-E, and other comorbidities with the SCID-IV and the MINI. Subjects were divided in early and late-onset groups (age of onset of impairment between 7 and 12 years old). The effect of age of onset over clinical and demographic characteristics was tested by regression models. Late-onset subjects were diagnosed later (P=0.04), had a lower frequency of problems with authority and discipline (P=0.004), and lower scores in SNAP-IV (P<0.001) and in Barkley's scale for problems in areas of life activities (P=0.03). On the other hand, late-onset patients presented a higher prevalence of comorbid general anxiety disorder (GAD) (P=0.01). Both groups had a similar profile in the remaining comorbidities and sociodemographic characteristics. This study provides initial evidence that adults with late-onset ADHD have less severity, lower frequency of externalizing symptoms and increased comorbidity with GAD, but similar profile in other comorbidities. In addition, the data suggest that late-onset patients have a higher probability of delayed diagnosis despite the significant impairment of their condition.

Body height and weight of patients with childhood onset and adult onset thyrotoxicosis.

PubMed

Takamatsu, J; Kobe, N; Ito, M; Ohsawa, N

1999-03-01

The present study has compared body height and weight of thyrotoxic female patients of childhood onset and adult onset. The body height of 141 out of 143 (99%) adult-onset thyrotoxic patients was within the range of mean +/- 2SD for the age-matched general Japanese female population. On the other hand, in 42 patients with childhood-onset thyrotoxicosis, 6 (14%) had their height being greater than the mean + 2SD of general population, and 34 (81%) were taller than the mean value. In 86 patients with siblings, 42 (49%) were at least 2 cm taller than their sisters, and 26 (30%) were more than 2 cm shorter than their sisters. The body weight of 27 out of 42 (68%) patients younger than 20 years was not decreased but was even greater than the mean value for the age-matched general population. The results indicate that excessive thyroid hormone in vivo enhances body height in humans. The increased body weight in some young patients suggests that enhanced dietary intake due to increased appetite in hyperthyroidism has overcome the energy loss with increased metabolism.

Patients with late-adult-onset ulcerative colitis have better outcomes than those with early onset disease.

PubMed

Ha, Christina Y; Newberry, Rodney D; Stone, Christian D; Ciorba, Matthew A

2010-08-01

The influence of age on the presentation, clinical course, and therapeutic response of patients with adult-onset ulcerative colitis (UC) is understudied. Given potential age-related differences in risk factors and immune function, we sought to determine if disease behavior or clinical outcomes differed between patients diagnosed with UC in later versus earlier stages of adulthood. We performed a retrospective cohort study of 295 patients with UC seen at a tertiary care center from 2001 to 2008. Adult subjects newly diagnosed with UC between the ages of 18 and 30 years were defined as early onset, those newly diagnosed at age 50 or older were defined as late onset. The 2 groups were analyzed for differences in medication use and clinical end points, including disease extent, severity at the time of diagnosis, and steroid-free clinical remission at 1 year after disease onset. Disease extent and symptom severity were similar between groups at the time of diagnosis. One year after diagnosis, more patients in the late-onset group achieved steroid-free clinical remission (64% vs 49%; P = .01). Among those who required systemic steroid therapy, more late-onset patients achieved steroid-free remission by 1 year (50% vs 32%; P = .01). Former smoking status was a more common risk factor in the late-onset cohort (P < .001), whereas more early onset patients had a positive family history (P = .008). Patients with early and late-adult-onset UC have similar initial clinical presentations, but differ in disease risk factors. Late-onset patients have better responses to therapy 1 year after diagnosis. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

Pre-adult versus adult onset major depressive disorder in a naturalistic patient sample: the Leiden Routine Outcome Monitoring Study.

PubMed

van Noorden, M S; Minkenberg, S E; Giltay, E J; den Hollander-Gijsman, M E; van Rood, Y R; van der Wee, N J; Zitman, F G

2011-07-01

Pre-adult onset of major depressive disorder (MDD) may predict a more severe phenotype of depression. As data from naturalistic psychiatric specialty care settings are scarce, we examined phenotypic differences between pre-adult and adult onset MDD in a large sample of consecutive out-patients. Altogether, 1552 out-patients, mean age 39.2 ± 11.6 years, were diagnosed with current MDD on the Mini-International Neuropsychiatric Interview Plus diagnostic interview as part of the usual diagnostic procedure. A total of 1105 patients (71.2%) had complete data on all variables of interest. Pre-adult onset of MDD was defined as having experienced the signs and symptoms of a first major depressive episode before the age of 18 years. Patients were stratified according to the age at interview (20-40/40-65 years). Correlates of pre-adult onset were analysed using logistic regression models adjusted for age, age squared and gender. Univariate analyses showed that pre-adult onset of MDD had a distinct set of demographic (e.g. less frequently living alone) and clinical correlates (more co-morbid DSM-IV - Text Revision diagnoses, more social phobia, more suicidality). In the multivariate model, we found an independent association only for a history of suicide attempts [odds ratio (OR) 3.15, 95% confidence intervals (CI) 1.97-5.05] and current suicidal thoughts (OR 1.81, 95% CI 1.26-2.60) in patients with pre-adult versus adult onset MDD. Pre-adult onset of MDD is associated with more suicidality than adult onset MDD. Age of onset of depression is an easy to ascertain characteristic that may help clinicians in weighing suicide risk.

Treatment and outcome of adult-onset neuroblastoma.

PubMed

Suzuki, Maya; Kushner, Brian H; Kramer, Kim; Basu, Ellen M; Roberts, Stephen S; Hammond, William J; LaQuaglia, Michael P; Wolden, Suzanne L; Cheung, Nai-Kong V; Modak, Shakeel

2018-03-25

Adult-onset neuroblastoma is rare and little is known about its biology and clinical course. There is no established therapy for adult-onset neuroblastoma. Anti-GD2 immunotherapy is now standard therapy in children with high-risk neuroblastoma; however, its use has not been reported in adults. Forty-four adults (18-71 years old) diagnosed with neuroblastoma between 1979 and 2015 were treated at Memorial Sloan Kettering Cancer Center. Five, 1, 5 and 33 patients had INSS stage 1, 2, 3 and 4 diseases, respectively. Genetic abnormalities included somatic ATRX (58%) and ALK mutations (42%) but not MYCN-amplification. In the 11 patients with locoregional disease, 10-year progression-free (PFS) and overall survival (OS) was 35.4 ± 16.1% and 61.4 ± 15.3%, respectively. Among 33 adults with stage 4 neuroblastoma, 7 (21%) achieved complete response (CR) after induction chemotherapy and/or surgery. Seven patients with primary refractory neuroblastoma (all with osteomedullary but no soft tissue disease) received anti-GD2 antibodies, mouse or humanized 3F8. Antibody-related adverse events were similar to those in children, response rate being 71.4%. In patients with stage 4 disease at diagnosis, 5-year PFS was 9.7± 5.3% and most patients who were alive with disease at 5 years died of neuroblastoma over the next 5 years, 10-year OS being only 19.0 ± 8.2%. Patients who achieved CR after induction had superior PFS and OS (p = 0.006, p = 0.031, respectively). Adult-onset neuroblastoma appeared to have different biology from pediatric or adolescent NB, and poorer outcome. Complete disease control appeared to improve long-term survival. Anti-GD2 immunotherapy was well tolerated and might be beneficial. © 2018 UICC.

Adult-onset Rasmussen encephalitis associated with focal cortical dysplasia.

PubMed

Hohenbichler, Katharina; Lelotte, Julie; Lhommel, Renaud; Tahry, Riëm El; Vrielynck, Pascal; Santos, Susana Ferrao

2017-12-01

Rasmussen encephalitis is a rare, devastating condition, typically presenting in childhood. Cases of adult-onset Rasmussen have also been described, but the clinical picture is less defined, rendering final diagnosis difficult. We present a case of adult-onset Rasmussen encephalitis with dual pathology, associated with focal cortical dysplasia and encephalitis. We interpreted the Rasmussen encephalitis to be caused by severe and continuous epileptic activity due to focal cortical dysplasia. The best therapeutic approach for such cases remains unclear.

Observing the onset of disability in older adults.

PubMed

Reynolds, Sandra L; Silverstein, Merril

2003-11-01

One of the greatest threats to the ability of older adults to live independently is the onset of disability in activities adults perform in their daily lives, such as dressing, eating, toileting, managing one's money, preparing meals and so on. This article examines the onset of disability in older adult Americans using three waves of the Asset and Health Dynamics Among the Oldest Old (AHEAD) survey (1993, 1995, 1998; n=4228). We use medical/demographic factors (arthritis, heart disease, diabetes; age, gender, race/ethnicity, wealth), baseline characteristics (affect, cognition, health behaviors, medical insurance), and time-varying covariates (changes in chronic conditions and baseline characteristics) to predict the onset of activities of daily living (ADLs) and instrumental activities of daily living (IADLs) disability, individually and in the aggregate, over time. We find the onset of ADL and IADL disability is a complex process, suggesting important roles for medical, demographic, social, psychological, and behavioral triggers, specifically negative affect, higher body weight, and by the lack of vigorous exercise. We also find that individual ADL and IADL impairments are predicted by a variety of different factors, suggesting that summary measures of disability may be masking a wealth of potentially useful interventions. In general, public health efforts in the area of controlling obesity and treating depressive symptoms should be supported.

Educational and vocational outcomes of adults with childhood- and adult-onset systemic lupus erythematosus: nine years of followup.

PubMed

Lawson, Erica F; Hersh, Aimee O; Trupin, Laura; von Scheven, Emily; Okumura, Megumi J; Yazdany, Jinoos; Yelin, Edward H

2014-05-01

To compare educational and vocational outcomes among adults with childhood-onset systemic lupus erythematosus (SLE) and adult-onset SLE. We used data derived from the 2002–2010 cycles of the Lupus Outcomes Study, a longitudinal cohort of 1,204 adult subjects with SLE. Subjects ages 18–60 years living in the US (n = 929) were included in the analysis and were classified as childhood-onset SLE if age at diagnosis was <18 years (n = 115). Logistic regression was used to assess the unadjusted and adjusted effect of childhood-onset SLE, sex, race/ethnicity, baseline age, urban or rural location, and US region on the likelihood of completing a bachelor's degree. Generalized estimating equations were used to assess the effect of childhood-onset SLE, demographics, education, and disease-related factors on the odds of employment, accounting for multiple observations over the study period. Subjects with childhood-onset SLE were on average younger (mean ± SD 29 ± 10 years versus 44 ± 9 years), with longer disease duration (mean ± SD 15 ± 10 years versus 11 ± 8 years). Subjects with adult-onset SLE and childhood-onset SLE subjects were equally likely to complete a bachelor's degree. However, subjects with childhood-onset SLE were significantly less likely to be employed, independent of demographic and disease characteristics (odds ratio 0.62, 95% confidence interval 0.42–0.91). While subjects with SLE are just as likely as those with adult-onset SLE to complete college education, childhood-onset SLE significantly increases the risk of not working in adulthood, even when controlling for disease and demographic factors. Exploring reasons for low rates of employment and providing vocational support may be important to maximize long-term functional outcomes in patients with childhood-onset SLE.

Vitrectomy for epiretinal membrane in adult-onset Coats' disease.

PubMed

Kumar, Pradeep; Kumar, Vinod

2017-10-01

Coats' disease is characterized by retinal vascular telangiectasia and subretinal and intraretinal exudation. A relatively benign form of the disease that occurs in adults is referred to as adult-onset Coats' disease. Involvement of macula in the form of macular edema and exudation are the common presenting features in both forms of the disease. We describe a rare case of adult-onset Coats' disease that presented with epiretinal membrane (ERM). Laser photocoagulation of retinal vascular telangiectasia resulted in worsening of patient's symptoms and ERM. Early pars plana vitrectomy resulted in resolution of the patient's symptoms. Utility of ultra-wide-field imaging and rationale of early vitrectomy in such cases are discussed.

Pneumonitis in Adult Onset Still's Disease: Uncommon or Under Diagnosed?

PubMed

Fernandes, Silvia; Almeida, Margarida; Pereira da Silva, José Alberto; Romeu, José Carlos

2017-08-31

The adult onset Still's Disease is an uncommon entity characterized by multiple clinical manifestations. Pneumonitis, less often considered, deserves particular emphasis given the need for differential diagnosis and because it can progress to severe respiratory failure. With the aim to highlight the pulmonary parenchyma involvement in patients with adult onset Still's Disease, we present a case report which progresses with pneumonitis.

Myotonic Dystrophy Initially Presenting as Tachycardiomyopathy Successful Catheter Ablation of Atrial Flutter

PubMed Central

Asbach, S.; Gutleben, K. J.; Dahlem, P.; Brachmann, J.; Nölker, G.

2010-01-01

Myotonic dystrophy is a genetic muscular disease that is frequently associated with cardiac arrhythmias. Bradyarrhythmias, such as sinus bradycardia and atrioventricular block, are more common than tachyarrhythmias. Rarely, previously undiagnosed patients with myotonic dystrophy initially present with a tachyarrhythmia. We describe the case of a 14-year-old boy, who was admitted to the hospital with clinical signs and symptoms of decompensated heart failure and severely reduced left ventricular function. Electrocardiography showed common-type atrial flutter with 2 : 1 conduction resulting in a heart rate of 160 bpm. Initiation of medical therapy for heart failure as well as electrical cardioversion led to a marked clinical improvement. Catheter ablation of atrial flutter was performed to prevent future cardiac decompensations and to prevent development of tachymyopathy. Left ventricular function normalized during followup. Genetic analysis confirmed the clinical suspicion of myotonic dystrophy as known in other family members in this case. PMID:20871860

Vitrectomy for epiretinal membrane in adult-onset Coats’ disease

PubMed Central

Kumar, Pradeep; Kumar, Vinod

2017-01-01

Coats’ disease is characterized by retinal vascular telangiectasia and subretinal and intraretinal exudation. A relatively benign form of the disease that occurs in adults is referred to as adult-onset Coats’ disease. Involvement of macula in the form of macular edema and exudation are the common presenting features in both forms of the disease. We describe a rare case of adult-onset Coats’ disease that presented with epiretinal membrane (ERM). Laser photocoagulation of retinal vascular telangiectasia resulted in worsening of patient's symptoms and ERM. Early pars plana vitrectomy resulted in resolution of the patient's symptoms. Utility of ultra-wide-field imaging and rationale of early vitrectomy in such cases are discussed. PMID:29044085

Lifetime Increased Risk of Adult Onset Atopic Dermatitis in Adolescent and Adult Patients with Food Allergy.

PubMed

Yu, Hsu-Sheng; Tu, Hung-Pin; Hong, Chien-Hui; Lee, Chih-Hung

2016-12-27

Food allergy can result in life-threatening anaphylaxis. Atopic dermatitis (AD) causes intense itching and impaired quality of life. Previous studies have shown that patients with classical early-onset AD tend to develop food allergy and that 10% of adults with food allergies have concomitant AD. However, it is not known whether late-onset food allergy leads to adult-onset AD, a recently recognized disease entity. Using an initial cohort of one-million subjects, this study retrospectively followed-up 2851 patients with food allergy (age > 12 years) for 14 years and compared them with 11,404 matched controls. While 2.8% (81) of the 2851 food allergy patients developed AD, only 2.0% (227) of the 11,404 controls developed AD. Multivariate regression analysis showed that food allergy patients were more likely to develop AD (adjusted hazard ratio = 2.49, p < 0.0001). Controls had a 1.99% risk of developing AD, while food allergy patients had a significantly higher risk (7.18% and 3.46% for patients with ≥3 and <3 food allergy claims, respectively) of developing adult-onset AD. This is the first study to describe the chronological and dose-dependent associations between food allergy in adolescence and the development of adult-onset AD.

Differences in disease features between childhood-onset and adult-onset systemic lupus erythematosus patients presenting with acute abdominal pain.

PubMed

Tu, Yu-Ling; Yeh, Kuo-Wei; Chen, Li-Chen; Yao, Tsung-Chieh; Ou, Liang-Shiou; Lee, Wen-I; Huang, Jing-Long

2011-04-01

Abdominal pain in systemic lupus erythematosus (SLE) patients has rarely been analyzed in pediatric populations. We planned to investigate the potential differences between childhood-onset and adult-onset SLE patients who were hospitalized because of acute abdominal pain. A retrospective study including 23 childhood-onset SLE patients with 38 admissions and 88 adult-onset SLE patients with 108 admissions from 1999 to 2008 were conducted in our hospital. All of them had the chief complaint of diffuse abdominal pain. The etiologies of acute abdominal pain in adult-onset SLE patients were more diverse than childhood-onset SLE patients. The most common cause of acute abdominal pain in SLE patients was lupus mesenteric vasculitis (LMV) (18.5%), followed by acute gastroenteritis (14.4%), pancreatitis (10.3%), appendicitis (7.5%), and cholecystitis (6.2%). Compared with adults, children were admitted more often due to LMV (31.6% versus 13.9%; P = 0.016), had more frequently recurrent episodes (39.1% versus 14.8%; P = 0.009), and were more often treated with immunosuppressive agents (31.6% versus 7.4%; P < 0.001) at the time of admission. The overall case fatality rate of acute abdomen in SLE patients was 9.4%. The extra-gastrointestinal symptoms, laboratory evaluation, disease activity, and organ damage measured by the SLE Disease Activity Index and outcomes were comparable between children and adults. Various etiologies of acute abdominal pain should be considered in SLE patients. LMV is the most common cause of acute abdomen in childhood-onset SLE patients with low mortality and morbidity provided by prompt diagnosis and timely administration of high-dose intravenous corticosteroids after excluding real surgical abdomen. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

Obesity's Effects on the Onset of Functional Impairment among Older Adults

ERIC Educational Resources Information Center

Jenkins, Kristi Rahrig

2004-01-01

Purpose: This study has two purposes. First, it determines if there is a relationship between body weight and the onset of functional impairment across time among this sample of older adults. More specifically, it examines if obese older adults are more likely to experience the onset of functional impairment. Second, it explores how health…

Adult-Onset Offending: A Neglected Reality? Findings From a Contemporary British General Population Cohort.

PubMed

Sapouna, Maria

2017-09-01

There is disagreement in the literature as to whether there are any true adult-onset offenders. The aim of this study is to investigate the prevalence and correlates of adult-onset offenders in a contemporary British general population cohort consisting of 739 individuals aged between 18 and 25 years. Sixteen percent of participants reported offending for the first time after the age of 18. It is concluded that adult-onset exists and deserves to be studied further. Adult-onset offenders were more likely to report using drugs, associating with deviant peers, and having mental health problems in adulthood than non-offenders. Compared with early-onset offenders, the adult-onset offenders were people with a stronger attachment to school, which may have protected them from the risk of offending in adolescence. It is possible that when that protection was removed in adulthood and they were exposed to negative life events, such as drug use and mental illness, they became involved in crime for the first time.

Social, educational and vocational outcomes in patients with childhood-onset and young-adult-onset growth hormone deficiency.

PubMed

Mitra, M Tanya; Jönsson, Peter; Åkerblad, Ann-Charlotte; Clayton, Peter; Kołtowska-Häggström, Maria; Korbonits, Márta; Toogood, Andy; Gleeson, Helena

2017-04-01

Hypopituitarism diagnosed in childhood, adolescence and young adulthood has the potential to affect growth and somatic development. Less is known about the impact of such a diagnosis on other aspects of development. An analysis of the KIMS database (Pfizer International Metabolic Database) was performed to explore social, educational and vocational outcomes of adult patients diagnosed in childhood, adolescence and young adulthood compared with adult-onset controls. A total of 2952 adult patients diagnosed with hypothalamic pituitary conditions before the age of 25 were divided into two groups: childhood-onset [<16 years (CO)] (n = 1782) and young-adult-onset [16 to <25 years (YAO)] (n = 1170). A total of 1617 adult patients diagnosed with a nonfunctioning pituitary adenoma at the age of 25 or older formed the adult-onset control group (AO). KIMS Patient Life Situation Form which provided information on social, educational and vocational outcomes. Compared with the AO control group, CO and YAO patients were between 4·5 and 8·0 times more likely to live with their parents in adulthood; CO and YAO patients were also less likely to live in partnership and to have children. The impact on educational and vocational outcomes was less marked than on social outcomes with no significant differences compared with the AO control group. Educational and vocational outcomes showed the lowest level in male and female CO and YAO patients who had been previously diagnosed with a brain tumour. Social outcomes were more affected than educational and vocational outcomes. Although CO patients are more adversely affected, YAO patients were also failing to achieve social milestones. This has consequences for the delivery of endocrine care in both paediatric and adult services. © 2016 John Wiley & Sons Ltd.

Myotonic dystrophy type 1, daytime sleepiness and REM sleep dysregulation.

PubMed

Dauvilliers, Yves A; Laberge, Luc

2012-12-01

Myotonic dystrophy type 1 (DM1), or Steinert's disease, is the most common adult-onset form of muscular dystrophy. DM1 also constitutes the neuromuscular condition with the most significant sleep disorders including excessive daytime sleepiness (EDS), central and obstructive sleep apneas, restless legs syndrome (RLS), periodic leg movements in wake (PLMW) and periodic leg movements in sleep (PLMS) as well as nocturnal and diurnal rapid eye movement (REM) sleep dysregulation. EDS is the most frequent non-muscular complaint in DM1, being present in about 70-80% of patients. Different phenotypes of sleep-related problems may mimic several sleep disorders, including idiopathic hypersomnia, narcolepsy without cataplexy, sleep apnea syndrome, and periodic leg movement disorder. Subjective and objective daytime sleepiness may be associated with the degree of muscular impairment. However, available evidence suggests that DM1-related EDS is primarily caused by a central dysfunction of sleep regulation rather than by sleep fragmentation, sleep-related respiratory events or periodic leg movements. EDS also tends to persist despite successful treatment of sleep-disordered breathing in DM1 patients. As EDS clearly impacts on physical and social functioning of DM1 patients, studies are needed to identify the best appropriate tools to identify hypersomnia, and clarify the indications for polysomnography (PSG) and multiple sleep latency test (MSLT) in DM1. In addition, further structured trials of assisted nocturnal ventilation and randomized trials of central nervous system (CNS) stimulant drugs in large samples of DM1 patients are required to optimally treat patients affected by this progressive, incurable condition. Copyright © 2012 Elsevier Ltd. All rights reserved.

Surgical Orthodontic Treatment of a Patient Affected by Type 1 Myotonic Dystrophy (Steinert Syndrome)

PubMed Central

Cacucci, Laura; Ricci, Beatrice; Moretti, Maria; Gasparini, Giulio; Pelo, Sandro

2017-01-01

Myotonic dystrophy, or Steinert's disease, is the most common form of muscular dystrophy that occurs in adults. This multisystemic form involves the skeletal muscles but affects also the eye, the endocrine system, the central nervous system, and the cardiac system. The weakness of the facial muscles causes a characteristic facial appearance frequently associated with malocclusions. Young people with myotonic dystrophy, who also have severe malocclusions, have bad oral functions such as chewing, breathing, and phonation. We present a case report of a 15-year-old boy with anterior open bite, upper and lower dental crowding, bilateral crossbite, and constriction of the upper jaw with a high and narrow palate. The patient's need was to improve his quality of life. Because of the severity of skeletal malocclusion, it was necessary to schedule a combined orthodontic and surgical therapy in order to achieve the highest aesthetic and functional result. Although therapy caused an improvement in patient's quality of life, the clinical management of the case was hard. The article shows a balance between costs and benefits of a therapy that challenges the nature of the main problem of the patient, and it is useful to identify the most appropriate course of treatment for similar cases. PMID:28642828

Surgical Orthodontic Treatment of a Patient Affected by Type 1 Myotonic Dystrophy (Steinert Syndrome).

PubMed

Cacucci, Laura; Ricci, Beatrice; Moretti, Maria; Gasparini, Giulio; Pelo, Sandro; Grippaudo, Cristina

2017-01-01

Myotonic dystrophy, or Steinert's disease, is the most common form of muscular dystrophy that occurs in adults. This multisystemic form involves the skeletal muscles but affects also the eye, the endocrine system, the central nervous system, and the cardiac system. The weakness of the facial muscles causes a characteristic facial appearance frequently associated with malocclusions. Young people with myotonic dystrophy, who also have severe malocclusions, have bad oral functions such as chewing, breathing, and phonation. We present a case report of a 15-year-old boy with anterior open bite, upper and lower dental crowding, bilateral crossbite, and constriction of the upper jaw with a high and narrow palate. The patient's need was to improve his quality of life. Because of the severity of skeletal malocclusion, it was necessary to schedule a combined orthodontic and surgical therapy in order to achieve the highest aesthetic and functional result. Although therapy caused an improvement in patient's quality of life, the clinical management of the case was hard. The article shows a balance between costs and benefits of a therapy that challenges the nature of the main problem of the patient, and it is useful to identify the most appropriate course of treatment for similar cases.

The distinction between juvenile and adult-onset primary open-angle glaucoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wiggs, J.L.; Haines, J.L.; Damji, K.F.

1996-01-01

Because of the significant differences between the juvenile and adult forms of open-angle glaucoma, especially with regard to inheritance, prevalence, severity, and age of onset, we read with interest the recent publication by Morissette et al., describing a pedigree with a phenotype that overlaps the distinctive features of juvenile-onset open-angle glaucoma (JOAG) and adult-onset primary open-angle glaucoma (usually abbreviated as POAG or COAG). These authors conclude that a gene mapped to human chromosome 1q21-q31 (GLC1A) can be responsible for both juvenile and adult forms of open-angle glaucoma. The implications of such a result could be extremely important, in light ofmore » the high prevalence of the adult form of the disease. However, while the data presented in this report suggest that variable expressivity of the GLC1A gene may lead to a broader range of onset for this form of juvenile glaucoma, these data do not identify the GLC1A gene as an important cause of POAG. To prevent misleading interpretations of this and similar studies, we wish to clarify the distinction between the juvenile and adult forms of open-angle glaucoma. 8 refs.« less

Adult-Onset Asthma Becomes the Dominant Phenotype among Women by Age 40 Years. The Longitudinal CARDIA Study

PubMed Central

Qualls, Clifford; Schuyler, Mark; Arynchyn, Alexander; Alvarado, Jesse H.; Smith, Lewis J.; Jacobs, David R.

2013-01-01

Rationale: Although asthma is usually considered to originate in childhood, adult-onset disease is being increasingly reported. Objectives: To contrast the proportion and natural history of adult-onset versus pediatric-onset asthma in a community-based cohort. We hypothesized that asthma in women is predominantly of adult onset rather than of pediatric onset. Methods: This study used data from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort in the United States over a 25-year period. Adult- and pediatric-onset asthma phenotypes were studied, as defined by age at onset of 18 years or older. Subjects with asthma were categorized by sex, obesity, atopy, smoking, and race by mean age/examination year, using a three-way analysis of covariance model. Natural history of disease was examined using probabilities derived from a Markov chain model. Measurements and Main Results: Asthma of adult onset became the dominant (i.e., exceeded 50%) phenotype in women by age 40 years. The age by which adult-onset asthma became the dominant phenotype was further lowered for obese, nonatopic, ever-smoking, or white women. The prevalence trend with increasing time for adult-onset disease was greater among subjects with nonatopic than atopic asthma among both sexes. Furthermore, adult-onset asthma had remarkable sex-related differences in risk factors. In both sexes, the quiescent state for adult-onset asthma was less frequent and also “less stable” over time than for pediatric-onset asthma. Conclusions: Using a large national cohort, this study challenges the dictum that most asthma in adults originates in childhood. Studies of the differences between pediatric- and adult-onset asthma may provide greater insight into the phenotypic heterogeneity of asthma. PMID:23802814

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. Copyright © 2014 Elsevier Inc. All rights reserved.

[Epidemiologic profile of juvenile-onset compared to adult-onset spondyloarthritis in a large Brazilian cohort].

PubMed

Duarte, Angela P; Marques, Cláudia D L; Bortoluzzo, Adriana B; Gonçalves, Célio R; da Silva, José Antonio Braga; Ximenes, Antonio Carlos; Bértolo, Manoel B; Ribeiro, Sandra Lúcia E; Keiserman, Mauro; Skare, Thelma L; Carneiro, Sueli; Menin, Rita; Azevedo, Valderilio F; Vieira, Walber P; Albuquerque, Elisa N; Bianchi, Washington A; Bonfiglioli, Rubens; Campanholo, Cristiano; Carvalho, Hellen M S; Costa, Izaias P; Kohem, Charles L; Leite, Nocy; Lima, Sonia A L; Meirelles, Eduardo S; Pereira, Ivânio A; Pinheiro, Marcelo M; Polito, Elizandra; Resende, Gustavo G; Rocha, Francisco Airton C; Santiago, Mittermayer B; Sauma, Maria de Fátima L C; Valim, Valéria; Sampaio-Barros, Percival D; Barros, Percival D Sampaio

2014-01-01

To analyze the clinical and epidemiologic characteristics of juvenile-onset spondyloarthritis (SpA) (< 16 years) and compare them with a group of adult-onset (≥ 16 years) SpA patients. Prospective, observational and multicentric cohort with 1,424 patients with the diagnosis of SpA according to the European Spondyloarthropathy Study Group (ESSG) submitted to a common protocol of investigation and recruited in 29 reference centers participants of the Brazilian Registry of Spondyloarthritis (RBE - Registro Brasileiro de Espondiloartrites). Patients were divided in two groups: age at onset<16 years (JOSpA group) and age at onset ≥ 16 years (AOSpA group). Among the 1,424 patients, 235 presented disease onset before 16 years (16.5%). The clinical and epidemiologic variables associated with JOSpA were male gender (p<0.001), lower limb arthritis (p=0.001), enthesitis (p=0.008), anterior uveitis (p=0.041) and positive HLA-B27 (p=0.017), associated with lower scores of disease activity (Bath Ankylosing Spondylitis Disease Activity Index - BASDAI; p=0.007) and functionality (Bath Ankylosing Spondylitis Functional Index - BASFI; p=0.036). Cutaneous psoriasis (p<0.001), inflammatory bowel disease (p=0.023), dactylitis (p=0.024) and nail involvement (p=0.004) were more frequent in patients with adult-onset SpA. Patients with JOSpA in this large Brazilian cohort were characterized predominantly by male gender, peripheral involvement (arthritis and enthesitis), positive HLA-B27 and lower disease scores. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

Epidemiology of adult-onset hydrocephalus: institutional experience with 2001 patients.

PubMed

Bir, Shyamal C; Patra, Devi Prasad; Maiti, Tanmoy K; Sun, Hai; Guthikonda, Bharat; Notarianni, Christina; Nanda, Anil

2016-09-01

OBJECTIVE Adult-onset hydrocephalus is not commonly discussed in the literature, especially regarding its demographic distribution. In contrast to pediatric hydrocephalus, which is related to a primary CSF pathway defect, its development in adults is often secondary to other pathologies. In this study, the authors investigated the epidemiology of adult-onset hydrocephalus as it pertains to different etiologies and in reference to age, sex, and race distributions. METHODS The authors retrospectively reviewed the clinical notes of 2001 patients with adult-onset hydrocephalus who presented to Louisiana State University Health Sciences Center within a 25-year span. Significant differences between the groups were analyzed by a chi-square test; p < 0.05 was considered significant. RESULTS The overall mean (± SEM) incidence of adult hydrocephalus in this population was 77 ± 30 per year, with a significant increase in incidence in the past decade (55 ± 3 [1990-2003] vs 102 ± 6 [2004-2015]; p < 0.0001). Hydrocephalus in a majority of the patients had a vascular etiology (45.5%) or was a result of a tumor (30.2%). The incidence of hydrocephalus in different age groups varied according to various pathologies. The incidence was significantly higher in males with normal-pressure hydrocephalus (p = 0.03) or head injury (p = 0.01) and higher in females with pseudotumor cerebri (p < 0.0001). In addition, the overall incidence of hydrocephalus was significantly higher in Caucasian patients (p = 0.0002) than in those of any other race. CONCLUSIONS Knowledge of the demographic variations in adult-onset hydrocephalus is helpful in achieving better risk stratification and better managing the disease in patients. For general applicability, these results should be validated in a large-scale meta-analysis based on a national population database.

Childhood-, teenage-, and adult-onset depression: diagnostic and individual characteristics in a clinical sample.

PubMed

Fernando, Kumari; Carter, Janet D; Frampton, Christopher M A; Luty, Suzanne E; McKenzie, Janice; Mulder, Roger T; Joyce, Peter R

2011-01-01

The age at which a depressive episode is first experienced may be associated with particular individual and clinical characteristics. This study compares individual, clinical, and family characteristics across individuals who experienced their first major depressive episode when a child, teenager, or adult. Participants were 372 depressed outpatients who participated in 2 completed randomized trials for depression. The first compared fluoxetine and nortriptyline, whereas the second compared cognitive behavior therapy and interpersonal psychotherapy. Assessment across the studies included structured clinical interviews for Diagnostic and Statistical Manual of Mental Disorders (DSM) Axis I/II diagnoses and a range of self-report measures of symptoms, functioning, and childhood experiences. Participants with childhood- and teenage-onset depression had a greater number of comorbid Axis I diagnoses, were more likely to meet criteria for Avoidant and Paranoid personality disorder (PD), and were more likely to have attempted suicide than those with adult-onset depression. Those with teenage-onset depression were more likely to meet criteria for a PD than those with adult-onset depression. Participants with childhood- and teenage-onset depression reported lower perceptions of paternal care before the age of 16 years, compared to participants with adult-onset depression. Retrospective recall was used to classify individuals into childhood-, teenage-, and adult-onset groups and is subject to recall biases. The sample also consisted of treatment-seeking individuals. There were relatively few differences between teenage and childhood depression. Depressive episodes that begin in childhood or teenage years are associated with more comorbid diagnoses, a higher likelihood of Avoidant and Paranoid PD, a greater likelihood of attempted suicide, and poorer perceptions of paternal care. Compared to adult-onset depression, childhood-onset depression is associated with greater

Quality of life in patients with myotonic dystrophy type 2.

PubMed

Rakocevic Stojanovic, Vidosava; Peric, Stojan; Paunic, Teodora; Pesovic, Jovan; Vujnic, Milorad; Peric, Marina; Nikolic, Ana; Lavrnic, Dragana; Savic Pavicevic, Dusanka

2016-06-15

To analyze quality of life (QoL) in a large cohort of myotonic dystrophy type 2 (DM2) patients in comparison to DM1 control group using both generic and disease specific questionnaires. In addition, we intended to identify different factors that might affect QoL of DM2 subjects. 49 DM2 patients were compared with 42 adult-onset DM1 patients. Patients completed SF-36 questionnaire and individualized neuromuscular quality of life questionnaire (INQoL). Following measures were also included: Medical Research Council 0-5 point scale for muscle strength, Addenbrooke's cognitive examination revised for cognitive status, Hamilton rating scale for depression, Krupp's fatigue severity scale and daytime sleepiness scale (DSS) RESULTS: SF-36 total score and physical composite score did not differ between DM1 and DM2 patients (p>0.05). However, role emotional and mental composite score were better in DM2 (p<0.05). INQoL total score was similar in both groups (p>0.05), although DM2 patients showed less impairment in independence (p<0.05) and body image domains (p<0.01). Regarding symptoms assessed by INQoL, DM2 patients showed less severe complaint of myotonia (p<0.01). Multiple linear regression analysis showed that significant predictors of worse QoL in DM2 patients were older age, worse muscle strength and higher level of fatigue. QoL reports of DM2 patients with the most severe form of the disease are comparable to those of DM1 patients. Special attention of clinicians should be paid to DM2 patients with older age, more severe muscle weakness and higher level of fatigue since they may be at higher risk to have worse QoL. Copyright © 2016 Elsevier B.V. All rights reserved.

Age at asthma onset and asthma self-management education among adults in the United States.

PubMed

Mirabelli, Maria C; Beavers, Suzanne F; Shepler, Samantha H; Chatterjee, Arjun B

2015-01-01

Asthma self-management education improves asthma-related outcomes. We conducted this analysis to evaluate variation in the percentages of adults with active asthma reporting components of asthma self-management education by age at asthma onset. Data from 2011 to 2012 Asthma Call-back Surveys were used to estimate percentages of adults with active asthma reporting six components of asthma self-management education. Components of asthma self-management education include having been taught to what to do during an asthma attack and receiving an asthma action plan. Differences in the percentages of adults reporting each component and the average number of components reported across categories of age at asthma onset were estimated using linear regression, adjusted for age, education, race/ethnicity, sex, smoking status, and years since asthma onset. Overall, an estimated 76.4% of adults with active asthma were taught what to do during an asthma attack and 28.7% reported receiving an asthma action plan. Percentages reporting each asthma self-management education component declined with increasing age at asthma onset. Compared with the referent group of adults whose asthma onset occurred at 5-14 years of age, the percentage of adults reporting being taught what to do during an asthma attack was 10% lower among those whose asthma onset occurred at 65-93 years of age (95% CI: -18.0, -2.5) and the average number of components reported decreased monotonically across categories of age at asthma onset of 35 years and older. Among adults with active asthma, reports of asthma self-management education decline with increasing age at asthma onset.

Modifications to toxic CUG RNAs induce structural stability, rescue mis-splicing in a myotonic dystrophy cell model and reduce toxicity in a myotonic dystrophy zebrafish model

DOE PAGES

deLorimier, Elaine; Coonrod, Leslie A.; Copperman, Jeremy; ...

2014-10-10

In this study, CUG repeat expansions in the 3' UTR of dystrophia myotonica protein kinase ( DMPK) cause myotonic dystrophy type 1 (DM1). As RNA, these repeats elicit toxicity by sequestering splicing proteins, such as MBNL1, into protein–RNA aggregates. Structural studies demonstrate that CUG repeats can form A-form helices, suggesting that repeat secondary structure could be important in pathogenicity. To evaluate this hypothesis, we utilized structure-stabilizing RNA modifications pseudouridine (Ψ) and 2'-O-methylation to determine if stabilization of CUG helical conformations affected toxicity. CUG repeats modified with Ψ or 2'-O-methyl groups exhibited enhanced structural stability and reduced affinity for MBNL1. Molecularmore » dynamics and X-ray crystallography suggest a potential water-bridging mechanism for Ψ-mediated CUG repeat stabilization. Ψ modification of CUG repeats rescued mis-splicing in a DM1 cell model and prevented CUG repeat toxicity in zebrafish embryos. This study indicates that the structure of toxic RNAs has a significant role in controlling the onset of neuromuscular diseases.« less

The experience of living with adult-onset epilepsy.

PubMed

Kılınç, Stephanie; van Wersch, Anna; Campbell, Carol; Guy, Alison

2017-08-01

The incidence and prevalence of adults diagnosed with epilepsy is higher compared to those diagnosed in childhood, yet the experience of living with adult-onset epilepsy has rarely been examined. Hence, the current study took a phenomenological approach to examining the experience of living with epilepsy following diagnosis in adulthood. Semi-structured interviews were conducted with 39 people from across the UK, diagnosed with epilepsy between the ages of eighteen and sixty, at two points in time, six months apart. Phenomenological analysis identified three central themes: the unpredictability of seizure occurrence; the ripple effect; and re-evaluating the future. Despite the accepted consensus in the epilepsy literature that living and coping with epilepsy becomes more difficult the older a person is diagnosed, the current findings indicated that this is inadequate. Rather, it is more suitable to consider that those living with adult-onset epilepsy have a specific experience of the condition and particular support needs, given that they once lived their lives as people without epilepsy. Copyright © 2017 Elsevier Inc. All rights reserved.

How Much Do We Know about Adult-onset Primary Tics? Prevalence, Epidemiology, and Clinical Features.

PubMed

Robakis, Daphne

2017-01-01

Tic disorders are generally considered to be of pediatric onset; however, reports of adult-onset tics exist in the literature. Tics can be categorized as either primary or secondary, with the latter being the larger group in adults. Primary or idiopathic tics that arise in adulthood make up a subset of tic disorders whose epidemiologic and clinical features have not been well delineated. Articles to be included in this review were identified by searching PubMed, SCOPUS, and Web of Science using the terms adult- and late-onset tics, which resulted in 120 unique articles. Duplicates were removed. Citing references were identified using Google Scholar; all references were reviewed for relevance. The epidemiologic characteristics, clinical phenomenology, and optimal treatment of adult-onset tics have not been ascertained. Twenty-six patients with adult-onset, primary tics were identified from prior case reports. The frequency of psychiatric comorbidities may be lower in adults than in children, and obsessive compulsive disorder was the most common comorbidity. Adult-onset primary tics tend to wax and wane, occur predominantly in males, are often both motor and phonic in the same individual, and are characterized by a poor response to treatment. We know little about adult-onset tic disorders, particularly ones without a secondary association or cause. They are not common, and from the limited data available, appear to share some but not all features with childhood tics. Further research will be important in gaining a better understanding of the epidemiology and clinical manifestations of this disorder.

How Much Do We Know about Adult-onset Primary Tics? Prevalence, Epidemiology, and Clinical Features

PubMed Central

Robakis, Daphne

2017-01-01

Background Tic disorders are generally considered to be of pediatric onset; however, reports of adult-onset tics exist in the literature. Tics can be categorized as either primary or secondary, with the latter being the larger group in adults. Primary or idiopathic tics that arise in adulthood make up a subset of tic disorders whose epidemiologic and clinical features have not been well delineated. Methods Articles to be included in this review were identified by searching PubMed, SCOPUS, and Web of Science using the terms adult- and late-onset tics, which resulted in 120 unique articles. Duplicates were removed. Citing references were identified using Google Scholar; all references were reviewed for relevance. Results The epidemiologic characteristics, clinical phenomenology, and optimal treatment of adult-onset tics have not been ascertained. Twenty-six patients with adult-onset, primary tics were identified from prior case reports. The frequency of psychiatric comorbidities may be lower in adults than in children, and obsessive compulsive disorder was the most common comorbidity. Adult-onset primary tics tend to wax and wane, occur predominantly in males, are often both motor and phonic in the same individual, and are characterized by a poor response to treatment. Discussion We know little about adult-onset tic disorders, particularly ones without a secondary association or cause. They are not common, and from the limited data available, appear to share some but not all features with childhood tics. Further research will be important in gaining a better understanding of the epidemiology and clinical manifestations of this disorder. PMID:28546883

Vitrectomy for full-thickness macular hole in adult-onset Coats’ disease

PubMed Central

Kumar, Vinod; Kumar, Pradeep; Garg, Gaurav; Damodaran, Saurabh

2017-01-01

The occurrence of full thickness macular hole in Coats’ disease is extremely rare. The purpose of this case report is to report pars plana vitrectomy for the treatment of full thickness macular hole in a patient with adult onset Coats disease. A young male presented with decreased vision in his right eye because of full thickness macular hole. The macular hole was found to be associated with adult onset Coats’ disease that was evident on ultra-wide field imaging. The patient underwent laser photocoagulation to the vascular telangiectasia followed by pars plana vitrectomy, large internal limiting membrane peeling and gas tamponade. This resulted in regression of exudation, closure of macular hole and improvement in vision. Coats disease of adult onset can present with decreased vision because of full thickness macular hole. Vitrectomy with internal limiting membrane peeling can result in excellent visual outcome. PMID:29133668

Stabilization in early adult-onset myopia with corneal refractive therapy.

PubMed

González-Méijome, José M; Carracedo, Gonzalo; Lopes-Ferreira, Daniela; Faria-Ribeiro, Miguel A; Peixoto-de-Matos, Sofia C; Queirós, António

2016-02-01

To describe the stabilization of early adult-onset myopia in three university students after initiating orthokeratology treatment with corneal refractive therapy contact lenses. Three Caucasian early adult-onset progressing myopic subjects (1 male, 2 females) were fitted with corneal refractive therapy lenses to correct myopia between -1.50 and -2.50 D of sphere using Paragon CRT (Paragon Vision Sciences, Mesa, AZ) lenses for overnight orthokeratology. The pre-treatment refractive history from 2005 as well as refraction and axial length after treatment onset are reported over a period of 3 years between December 2009 and January 2013 with an additional year of follow-up after treatment discontinuation (January-December 2013). The peripheral refractive patterns and topographic changes are also reported individually. Treatment was successful in all three subjects achieving uncorrected visual acuity of 20/20 or better monocularly. During a period of 3 years of follow-up the subjects did not experience progression in their refractive error, nor in their axial length (measured during the last 2 years of treatment and 1 year after discontinuation). Furthermore, the subjects recovered to their baseline refraction and did not progressed further over the following year after lens wear discontinuation. We cannot attribute a causative effect to the orthokeratology treatment alone as underlying mechanism for myopia stabilization in this 3 patients. However, the present report points to the possibility of stabilization of early adult-onset myopia progression in young adults using corneal refractive therapy treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

De Novo Advanced Adult-Onset Offending: New Evidence from a Population of Federal Correctional Clients.

PubMed

DeLisi, Matt; Tahja, Katherine N; Drury, Alan J; Elbert, Michael J; Caropreso, Daniel E; Heinrichs, Timothy

2018-01-01

Adult antisocial behavior is almost always predated by delinquency during childhood or adolescence; however, there is also evidence of adult-onset criminal offending. This study examined this controversial subgroup of offenders using self-reported and official data from a total population of federal correctional clients selected from the Midwestern United States. Difference of means t-tests, chi-square tests, and logistic regression models found that 11.7% of clients had an adult onset of offending and 2.7% of clients (n = 23) had an onset occurring at age 60 years or older. This group-introduced as de novo advanced adult-onset offenders-had high socioeconomic status, mixed evidence of adverse childhood experiences, and virtually no usage of drugs with the exception of alcohol. These offenders were primarily convicted of social security and white-collar crimes and evinced remarkably low psychopathology and criminal risk. More research is needed to replicate the phenomenon of de novo advanced adult-onset offending. © 2017 American Academy of Forensic Sciences.

Epidemiological, clinical and genetic aspects of adult onset isolated focal dystonia in Ireland.

PubMed

Williams, L; McGovern, E; Kimmich, O; Molloy, A; Beiser, I; Butler, J S; Molloy, F; Logan, P; Healy, D G; Lynch, T; Walsh, R; Cassidy, L; Moriarty, P; Moore, H; McSwiney, T; Walsh, C; O'Riordan, S; Hutchinson, M

2017-01-01

Adult onset idiopathic isolated focal dystonia presents with a number of phenotypes. Reported prevalence rates vary considerably; well-characterized cohorts are important to our understanding of this disorder. To perform a nationwide epidemiological study of adult onset idiopathic isolated focal dystonia in the Republic of Ireland. Patients with adult onset idiopathic isolated focal dystonia were recruited from multiple sources. Diagnosis was based on assessment by a neurologist with an expertise in movement disorders. When consent was obtained, a number of clinical features including family history were assessed. On the prevalence date there were 592 individuals in Ireland with adult onset idiopathic isolated focal dystonia, a point prevalence of 17.8 per 100 000 (95% confidence interval 16.4-19.2). Phenotype numbers were cervical dystonia 410 (69.2%), blepharospasm 102 (17.2%), focal hand dystonia 39 (6.6%), spasmodic dysphonia 18 (3.0%), musician's dystonia 17 (2.9%) and oromandibular dystonia six (1.0%). Sixty-two (16.5%) of 375 consenting index cases had a relative with clinically confirmed adult onset idiopathic isolated focal dystonia (18 multiplex and 24 duplex families). Marked variations in the proportions of patients with tremor, segmental spread, sensory tricks, pain and psychiatric symptoms by phenotype were documented. The prevalence of adult onset idiopathic isolated focal dystonia in Ireland is higher than that recorded in many similar service-based epidemiological studies but is still likely to be an underestimate. The low proportion of individuals with blepharospasm may reflect reduced environmental exposure to sunlight in Ireland. This study will serve as a resource for international comparative studies of environmental and genetic factors in the pathogenesis of the disorder. © 2016 EAN.

Sporadic adult onset primary torsion dystonia is a genetic disorder by the temporal discrimination test.

PubMed

Kimmich, Okka; Bradley, David; Whelan, Robert; Mulrooney, Nicola; Reilly, Richard B; Hutchinson, Siobhan; O'Riordan, Sean; Hutchinson, Michael

2011-09-01

Adult-onset primary torsion dystonia is an autosomal dominant disorder with markedly reduced penetrance; patients with sporadic adult-onset primary torsion dystonia are much more prevalent than familial. The temporal discrimination threshold is the shortest time interval at which two stimuli are detected to be asynchronous and has been shown to be abnormal in adult-onset primary torsion dystonia. The aim was to determine the frequency of abnormal temporal discrimination thresholds in patients with sporadic adult-onset primary torsion dystonia and their first-degree relatives. We hypothesized that abnormal temporal discrimination thresholds in first relatives would be compatible with an autosomal dominant endophenotype. Temporal discrimination thresholds were examined in 61 control subjects (39 subjects <50 years of age; 22 subjects >50 years of age), 32 patients with sporadic adult-onset primary torsion dystonia (cervical dystonia n = 30, spasmodic dysphonia n = 1 and Meige's syndrome n = 1) and 73 unaffected first-degree relatives (36 siblings, 36 offspring and one parent) using visual and tactile stimuli. Z-scores were calculated for all subjects; a Z > 2.5 was considered abnormal. Abnormal temporal discrimination thresholds were found in 1/61 (2%) control subjects, 27/32 (84%) patients with adult-onset primary torsion dystonia and 32/73 (44%) unaffected relatives [siblings (20/36; 56%), offspring (11/36; 31%) and one parent]. When two or more relatives were tested in any one family, 22 of 24 families had at least one first-degree relative with an abnormal temporal discrimination threshold. The frequency of abnormal temporal discrimination thresholds in first-degree relatives of patients with sporadic adult-onset primary torsion dystonia is compatible with an autosomal dominant disorder and supports the hypothesis that apparently sporadic adult-onset primary torsion dystonia is genetic in origin.

Fluid Distribution Pattern in Adult-Onset Congenital, Idiopathic, and Secondary Normal-Pressure Hydrocephalus: Implications for Clinical Care.

PubMed

Yamada, Shigeki; Ishikawa, Masatsune; Yamamoto, Kazuo

2017-01-01

In spite of growing evidence of idiopathic normal-pressure hydrocephalus (NPH), a viewpoint about clinical care for idiopathic NPH is still controversial. A continuous divergence of viewpoints might be due to confusing classifications of idiopathic and adult-onset congenital NPH. To elucidate the classification of NPH, we propose that adult-onset congenital NPH should be explicitly distinguished from idiopathic and secondary NPH. On the basis of conventional CT scan or MRI, idiopathic NPH was defined as narrow sulci at the high convexity in concurrent with enlargement of the ventricles, basal cistern and Sylvian fissure, whereas adult-onset congenital NPH was defined as huge ventricles without high-convexity tightness. We compared clinical characteristics and cerebrospinal fluid distribution among 85 patients diagnosed with idiopathic NPH, 17 patients with secondary NPH, and 7 patients with adult-onset congenital NPH. All patients underwent 3-T MRI examinations and tap-tests. The volumes of ventricles and subarachnoid spaces were measured using a 3D workstation based on T2-weighted 3D sequences. The mean intracranial volume for the patients with adult-onset congenital NPH was almost 100 mL larger than the volumes for patients with idiopathic and secondary NPH. Compared with the patients with idiopathic or secondary NPH, patients with adult-onset congenital NPH exhibited larger ventricles but normal sized subarachnoid spaces. The mean volume ratio of the high-convexity subarachnoid space was significantly less in idiopathic NPH than in adult-onset congenital NPH, whereas the mean volume ratio of the basal cistern and Sylvian fissure in idiopathic NPH was >2 times larger than that in adult-onset congenital NPH. The symptoms of gait disturbance, cognitive impairment, and urinary incontinence in patients with adult-onset congenital NPH tended to progress more slowly compared to their progress in patients with idiopathic NPH. Cerebrospinal fluid distributions and

Adult onset Leigh syndrome with mitochondrial DNA 8344 A>G mutation.

PubMed

Han, Jee-Young; Sung, Jung-Joon; Park, Hong-Kyun; Yoon, Byung-Nam; Lee, Kwang-Woo

2014-11-01

We report a pedigree of adult-onset Leigh syndrome (LS) with mitochondrial mutation 8344 A>G. A 38-year-old woman presented with optic neuropathy, weakness and cognitive impairment. Family history of optic neuropathy and systemic involvement was suggestive of mitochondrial encephalopathy. Genetic and radiologic studies showed m.8344 A>G mutation with characteristics of LS. To our knowledge this is the first case of adult-onset LS demonstrating the m.8344 A>G mutation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Unmasked adult-onset urea cycle disorders in the critical care setting.

PubMed

Summar, Marshall L; Barr, Frederick; Dawling, Sheila; Smith, Wendy; Lee, Brendan; Singh, Rani H; Rhead, William J; Sniderman King, Lisa; Christman, Brian W

2005-10-01

Most often, urea cycle disorders have been described as acute onset hyperammonemia in the newborn period; however, there is a growing awareness that urea cycle disorders can present at almost any age, frequently in the critical care setting. This article presents three cases of adult-onset hyperammonemia caused by inherited defects in nitrogen processing in the urea cycle, and reviews the diagnosis, management, and pathophysiology of adult-onset urea cycle disorders. Individuals who have milder molecular urea cycle defects can lead a relatively normal life until a severe environmental stress triggers a hyperammonemic crisis. Comorbid conditions such as physical trauma often delay the diagnosis of the urea cycle defect. Prompt recognition and treatment are essential in determining the outcome of these patients.

Etiopathogenesis and Therapeutic Approach to Adult Onset Acne

PubMed Central

Kaur, Sarabjit; Verma, Poonam; Sangwan, Ankita; Dayal, Surabhi; Jain, Vijay Kumar

2016-01-01

Acne vulgaris is usually considered as a skin disorder that primarily affects adolescents reaching a peak at the age of 14–17 years in females and 16–19 years in males. However, recent epidemiologic studies have shown that a significant number of female patients aged >25 years experience acne. As it is regarded as a disease of teenagers, adults are more apprehensive and experience social anxiety. Hence, adult onset acne has become a matter of concern. PMID:27512185

Prevalence and clinical characteristics of adult-onset atopic dermatitis with positive skin prick testing to mites.

PubMed

Kulthanan, Kanokvalai; Chularojanamontri, Leena; Manapajon, Araya; Nuchkull, Piyavadee

2011-12-01

The clinical role of house dust mite (HDM) in atopic dermatitis (AD) is still controversial. The aim of the study is to assess the prevalence, clinical relevance and characteristics of adult-onset AD patients with positive skin prick tests (SPT) to mites. The case record forms of adult-onset AD patients who underwent SPT at the Skin Allergy Clinic, Siriraj Hospital were reviewed. Forty-one of 62 patients (66.1%) had positive SPT to mites. The frequency of intrinsic AD among adult-onset AD was 4.8% (3/62). SPT to HDM tended to be positive in patients who had personal or family history of atopy, positive SPT to several specific antigens or who presented with elevated serum IgE, chelitis, recurrent conjunctivitis and perifollicular accentuation, respectively. CONCLUSION The prevalence of adult-onset AD patients with mite sensitivity was high. There were some notable features that tended to be present in mite sensitive adult-onset AD patients.

Age-Related Sexual Dimorphism in Temporal Discrimination and in Adult-Onset Dystonia Suggests GABAergic Mechanisms.

PubMed

Butler, John S; Beiser, Ines M; Williams, Laura; McGovern, Eavan; Molloy, Fiona; Lynch, Tim; Healy, Dan G; Moore, Helena; Walsh, Richard; Reilly, Richard B; O'Riordan, Seán; Walsh, Cathal; Hutchinson, Michael

2015-01-01

Adult-onset isolated focal dystonia (AOIFD) presenting in early adult life is more frequent in men, whereas in middle age it is female predominant. Temporal discrimination, an endophenotype of adult-onset idiopathic isolated focal dystonia, shows evidence of sexual dimorphism in healthy participants. We assessed the distinctive features of age-related sexual dimorphism of (i) sex ratios in dystonia phenotypes and (ii) sexual dimorphism in temporal discrimination in unaffected relatives of cervical dystonia patients. We performed (i) a meta-regression analysis of the proportion of men in published cohorts of phenotypes of adult-onset dystonia in relation to their mean age of onset and (ii) an analysis of temporal discrimination thresholds in 220 unaffected first-degree relatives (125 women) of cervical dystonia patients. In 53 studies of dystonia phenotypes, the proportion of men showed a highly significant negative association with mean age of onset (p < 0.0001, pseudo-R (2) = 59.6%), with increasing female predominance from 40 years of age. Age of onset and phenotype together explained 92.8% of the variance in proportion of men. Temporal discrimination in relatives under the age of 35 years is faster in women than men but the age-related rate of deterioration in women is twice that of men; after 45 years of age, men have faster temporal discrimination than women. Temporal discrimination in unaffected relatives of cervical dystonia patients and sex ratios in adult-onset dystonia phenotypes show similar patterns of age-related sexual dimorphism. Such age-related sexual dimorphism in temporal discrimination and adult-onset focal dystonia may reflect common underlying mechanisms. Cerebral GABA levels have been reported to show similar age-related sexual dimorphism in healthy participants and may be the mechanism underlying the observed age-related sexual dimorphism in temporal discrimination and the sex ratios in AOIFD.

Multicentric prevalence study of anti P ribosomal autoantibodies in juvenile onset systemic lupus erythematosus compared with adult onset systemic lupus erythematosus.

PubMed

Pisoni, Cecilia N; Muñoz, Sebastián Andrés; Carrizo, Carolina; Cosatti, Micaela; Álvarez, Analía; Dubinsky, Diana; Bresan, Eleonora; Russo, Ricardo; Borgia, Ezequiel; García, Mercedes; Sansinanea, Pierina; Basta, María Cristina; D'Amico, Maria Agustina; Barreira, Juan Carlos; Lancioni, Eliana; Soriano, Enrique; Cunto, Carmen de; Beron, Ana; Eimon, Alicia

2015-01-01

To investigate the prevalence and associations with clinical manifestations of anti- P ribosomal antibodies in patients with juvenile-onset and adult-onset systemic lupus erythematosus (SLE). Clinical and serological data of 30 patients with juvenile-onset SLE (age at onset younger than 16 years old) were compared with data of 92 patients with adult-onset SLE. Symptoms occurring during the entire disease course were considered. Anti- P ribosomal antibodies were tested by ELISA. Anti- P ribosomal antibodies were found significantly more often in pediatric-onset SLE patients (26.7% vs. 6.5%; OR=5.21 [CI95%=1.6-16.5], p=0.003). Alopecia (OR=10.11, CI 95%=1.25-97) and skin rash (non discoid) (OR=4.1, CI 95%=1.25-13.89) were significantly associated with anti- P ribosomal antibodies. Anti-ribosomal P antibodies are more often found in patients with juvenile SLE. Alopecia and skin rash were the only clinical manifestations associated to anti-ribosomal P antibodies. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Cyclic Vomiting Syndrome (CVS): is there a difference based on onset of symptoms--pediatric versus adult?

PubMed

Kumar, Nilay; Bashar, Qumseya; Reddy, Naveen; Sengupta, Jyotirmoy; Ananthakrishnan, Ashwin; Schroeder, Abigail; Hogan, Walter J; Venkatesan, Thangam

2012-05-28

Cyclic Vomiting Syndrome (CVS) is a well-recognized functional gastrointestinal disorder in children but its presentation is poorly understood in adults. Genetic differences in pediatric-onset (presentation before age 18) and adult-onset CVS have been reported recently but their clinical features and possible differences in response to therapy have not been well studied. This was a retrospective review of 101 CVS patients seen at the Medical College of Wisconsin between 2006 and 2008. Rome III criteria were utilized to make the diagnosis of CVS. Our study population comprised of 29(29%) pediatric-onset and 72 (71%) adult-onset CVS patients. Pediatric-onset CVS patients were more likely to be female (86% vs. 57%, p = 0.005) and had a higher prevalence of CVS plus (CVS + neurocognitive disorders) as compared to adult-onset CVS patients (14% vs. 3%, p = 0.05). There was a longer delay in diagnosis (10 ± 7 years) in the pediatric-onset group when compared to (5 ± 7 years) adult-onset CVS group (p = 0.001). Chronic opiate use was less frequent in the pediatric-onset group compared to adult-onset patients (0% vs. 23%, p = 0.004). Aside from these differences, the two groups were similar with regards to their clinical features and the time of onset of symptoms did not predict response to standard treatment. The majority of patients (86%) responded to treatment with tricyclic antidepressants, anticonvulsants (topiramate), coenzyme Q-10, and L-carnitine. Non-response to therapy was associated with coalescence of symptoms, chronic opiate use and more severe disease as characterized by longer episodes, greater number of emergency department visits in the year prior to presentation, presence of disability and non-compliance on univariate analysis. On multivariate analysis, only compliance to therapy was associated with a response. (88% vs. 38%, Odds Ratio, OR 9.6; 95% Confidence Interval [CI], 1.18-77.05). Despite reported genetic differences, the clinical features and

Laparoscopic cholecystectomy in a patient with Steinert myotonic dystrophy. Case report.

PubMed

Agrusa, A; Mularo, S; Alessi, R; Di Paola, P; Mularo, A; Amato, G; Romano, G

2011-01-01

Myotonic dystrophy (MD) is a serious multi-systemic autosomal dominant disease. The estimated incidence is 1 in every 8000 births, with an estimated prevalence of between 2.1 and 14.3 cases per 100,000 inhabitants. Signs and symptoms vary from a severe form of congenital myopathy, present from birth and often fatal, to a classic form and a delayed form, which generally presents after the age of 50 and in which the only sign is a cataract and life expectancy is completely normal. We describe the clinical case of a 40-year-old woman with Steinert myotonic dystrophy who underwent laparoscopic cholecystectomy (under general anesthesia) for symptomatic gallbladder stones. The conduct of anesthesia in such patients must be carefully considered, as hypothermia, shivering, electrical and mechanical stimulation, and the drugs used can all trigger myotonia.

A comparison between nailfold capillaroscopy patterns in adulthood in juvenile and adult-onset systemic sclerosis: A EUSTAR exploratory study.

PubMed

Ingegnoli, Francesca; Boracchi, Patrizia; Gualtierotti, Roberta; Smith, Vanessa; Cutolo, Maurizio; Foeldvari, Ivan

2015-11-01

Qualitative capillaroscopy patterns in juvenile- and adult-onset systemic sclerosis (SSc) were studied in adulthood using data from the EULAR Scleroderma Trials and Research (EUSTAR) database. Data collected between June 2004 and April 2013 were examined with focus on capillaroscopy. In this retrospective exploratory study, series of patients with juvenile-onset SSc were matched with series of adult-onset SSc having the same gender and autoantibody profile. 30 of 123 patients with juvenile-onset and 2108 of 7133 with adult-onset SSc had data on capillaroscopy. Juvenile-onset SSc showed scleroderma pattern more frequently than adult-onset SSc (93.3% and 88%). The OR was 2.44 and 95% CI 0.57-10.41. An active scleroderma pattern was present in 58% of juvenile- and 61% of adult-onset SSc. The OR was 0.91 and 95% CI 0.28-2.93. The late scleroderma pattern was present in 61% of juvenile- and 55.5% of adult-onset SSc. The OR was 1.06 and 95% CI 0.34-3.56. This is the first exploratory study on the comparison of capillaroscopy between juvenile- and adult-onset SSc in adulthood. Juvenile-onset SSc had an increase prevalence of scleroderma pattern, but a similar distribution of the three patterns was suggested. Further studies are needed to define this issue. Copyright © 2015 Elsevier Inc. All rights reserved.

Adult onset subacute sclerosing panencephalitis: clinical profile of 39 patients from a tertiary care centre

PubMed Central

Prashanth, L K; Taly, A B; Ravi, V; Sinha, S; Arunodaya, G R

2006-01-01

Clinical and laboratory characteristics of 39 patients with adult onset subacute sclerosing panencephalitis (SSPE) are described and compared to those of juvenile onset patients regarding preceding measles, age at onset, gender, interval between onset and diagnosis, clinical profile, and course during follow up. Diagnosis was based on clinical and electroencephalographic findings and raised anti‐measles antibody titres in cerebrospinal fluid. Mean age at SSPE symptom onset was 20.9±4.9 years and mean interval from onset to diagnosis was 6.3±9.6 months. Referral diagnosis was accurate in only 12 patients. Presenting symptoms included myoclonus, behavioural changes, seizures, and cognitive, visual, and extrapyramidal disturbance. All patients received symptomatic therapy; 19 also received disease modifying agents. Five of seven pregnant women had successful deliveries. The follow‐up period varied widely (maximum 60 months, median 9 months). The profile of adult onset SSPE did not differ from the rest of the cohort, except for a longer interval between measles infection and symptom onset (p<0.0001). SSPE in adults poses diagnostic challenges for clinicians. A high index of suspicion and appropriate investigations are necessary for early diagnosis and counselling. PMID:16464898

Adult outcomes of childhood-onset rheumatic diseases

PubMed Central

Hersh, Aimee; von Scheven, Emily; Yelin, Ed

2013-01-01

A number of studies published over the past 10 years have examined the long-term health, functional and quality of life outcomes of adults with childhood-onset rheumatic diseases such as juvenile idiopathic arthritis, systemic lupus erythematosus, juvenile dermatomyositis and localized scleroderma. As increasing numbers of patients with these conditions survive into adulthood, understanding the adult outcomes of these pediatric conditions has become ever-more important. Identifying modifiable risk factors for poor outcomes is vital to improving care for these patients. In addition, as these conditions and their treatments can affect cardiovascular health, bone health and fertility, particular attention needs to be paid to these outcomes. Preparing patients and their families for a successful transition from pediatric to adult rheumatology care is an important first-step in the long-term management strategy for this expanding patient population. PMID:21487383

The Need for Improved Detection and Management of Adult-Onset Hearing Loss in Australia

PubMed Central

McMahon, Catherine M.; Gopinath, Bamini; Schneider, Julie; Reath, Jennifer; Hickson, Louise; Leeder, Stephen R.; Mitchell, Paul; Cowan, Robert

2013-01-01

Adult-onset hearing loss is insidious and typically diagnosed and managed several years after onset. Often, this is after the loss having led to multiple negative consequences including effects on employment, depressive symptoms, and increased risk of mortality. In contrast, the use of hearing aids is associated with reduced depression, longer life expectancy, and retention in the workplace. Despite this, several studies indicate high levels of unmet need for hearing health services in older adults and poor use of prescribed hearing aids, often leading to their abandonment. In Australia, the largest component of financial cost of hearing loss (excluding the loss of well-being) is due to lost workplace productivity. Nonetheless, the Australian public health system does not have an effective and sustainable hearing screening strategy to tackle the problem of poor detection of adult-onset hearing loss. Given the increasing prevalence and disease burden of hearing impairment in adults, two key areas are not adequately met in the Australian healthcare system: (1) early identification of persons with chronic hearing impairment; (2) appropriate and targeted referral of these patients to hearing health service providers. This paper reviews the current literature, including population-based data from the Blue Mountains Hearing Study, and suggests different models for early detection of adult-onset hearing loss. PMID:23710184

Total intravenous anesthesia in a 10-month-old patient with congenital myotonic dystrophy undergoing endoscopic third ventriculostomy -A case report-

PubMed Central

Joh, Jung Hwa; Kim, Ji Yeon; Baek, Seung-Hye; Song, Jun-Gol; Lee, Yu Mi

2012-01-01

Myotonic dystrophy is a rare genetic disorder characterized by muscle atrophy and weakness. Surgical treatment of this condition poses various problems for the anesthesiologist. We describe the anesthetic management of a 10-month-old infant with congenital myotonic dystrophy, who was scheduled for endoscopic third ventriculostomy under general anesthesia. Anesthesia was induced with thiopental sodium, fentanyl, and vecuronium, and thereafter maintained via continuous infusion of propofol and remifentanil. The train-of-four ratio was monitored throughout the operation, and muscle relaxation was reversed with pyridostigmine and glycopyrrolate at the end of the procedure. We show that total intravenous anesthesia using propofol and remifentanil is a satisfactory anesthetic technique in very young patients with congenital myotonic dystrophy. PMID:22949987

INCREASED PROSPECTIVE HEALTH SERVICE USE FOR DEPRESSION AMONG ADULTS WITH CHILDHOOD ONSET BIPOLAR DISORDER

PubMed Central

Sala, Regina; Goldstein, Benjamin I.; Wang, Shuai; Flórez-Salamanca, Ludwing; Iza, Miren; Blanco, Carlos

2013-01-01

Objective To examine the prospective relationship between age of onset of bipolar disorder and the demographic and clinical characteristics, treatment, new onset of psychiatric comorbidity, and psychosocial functioning among adults with bipolar disorder. Study design As part of the National Epidemiologic Survey on Alcohol and Related Conditions, 1600 adults who met lifetime DSM-IV criteria for bipolar disorder-I (n=1172) and bipolar disorder-II (n=428) were included. Individuals were evaluated using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DMS-IV Version and data was analyzed from Waves 1 and 2, approximately 3 years apart. Individuals with bipolar disorder were divided into three age at onset groups: childhood (<13 years old, n=115), adolescence (13-18 years old, n=396), and adulthood (>19 year old, n=1017). Results After adjusting for confounding factors, adults with childhood-onset bipolar disorder were more likely to see a counselor, have been hospitalized and have received emergency room treatment for depression compared with those with adulthood-onset bipolar disorder. By contrast, there were no differences in the severity of mania or hypomania, new onset of comorbidity, and psychosocial functioning by age of bipolar disorder onset. Conclusions Childhood-onset bipolar disorder is prospectively associated with seeking treatment for depression, an important proxy for depressive severity. Longitudinal studies are needed in order to determine whether prompt identification, accurate diagnosis, and early intervention can serve to mitigate the burden of childhood onset on the long-term depressive burden of bipolar disorder. PMID:23896190

Comparison of Neuropsychological Functioning Between Adults With Early- and Late-Onset DSM-5 ADHD.

PubMed

Lin, Yu-Ju; Gau, Susan Shur-Fen

2017-09-01

We aimed to compare the visually dependent neuropsychological functioning among adults with Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) ADHD who recalled symptom onset by and after age 7 and non-ADHD controls. We divided the participants, aged 17 to 40 years, into three groups-(a) ADHD, onset <7 years (early-onset, n = 142); (b) ADHD, onset between 7 and <12 years (late-onset, n = 41); (c) non-ADHD controls ( n = 148)-and compared their neuropsychological functioning, measured by the Cambridge Neuropsychological Testing Automated Battery. Both ADHD groups had deficits in attention and signal detectability, spatial working memory, and short-term spatial memory, but only the early-onset group showed deficits in alertness, set-shifting, and planning after controlling for age, sex, and psychiatric comorbidities. There was no statistical difference between the two ADHD groups in neuropsychological functioning. DSM-5 criteria for diagnosing adult ADHD are not too lax regarding neuropsychological functioning.

The Evidence-Based Approach to Adult-Onset Idiopathic Nephrotic Syndrome.

PubMed

Canetta, Pietro A A; Radhakrishnan, Jai

2015-01-01

Adult-onset nephrotic syndrome (NS) differs from its pediatric counterpart in several important ways. Most importantly, NS in adults is more etiologically heterogeneous compared to children, and thus treatment approaches rely heavily on the histological diagnosis provided by renal biopsy. The evidence-based approach to treatment of adult NS has been critically examined by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines in glomerulonephritis, published in 2012. Here, we examine the strengths and limits of those guidelines and review recent work that expands the evidence-based approach.

Non-atopic males with adult onset asthma are at risk of persistent airflow limitation.

PubMed

Amelink, M; de Nijs, S B; Berger, M; Weersink, E J; ten Brinke, A; Sterk, P J; Bel, E H

2012-05-01

Patients with asthma have on average a more rapid decline in FEV (1) as compared with the general population. Recent cluster analysis has revealed different asthma phenotypes that can be distinguished by age of onset and reversibility of airflow limitation. This study aimed at detecting risk factors associated with persistent airflow limitation in patients with the adult onset asthma phenotype. We recruited 88 patients with adult onset (≥ 18 years) asthma from an academic pulmonary outpatient clinic in the Netherlands. The associations of age, age of asthma onset, asthma duration, gender, race, atopy, smoking pack-years, BMI, use of oral corticosteroids with post-bronchodilator FEV (1) /FVC were investigated. Multiple linear regression analysis showed an association of absence of atopy (r = -0.27, B = -0.26, P = 0.01) and male gender (r = 0.31, B = 0.30, P = 0.004) with post-bronchodilator FEV (1) /FVC. Multiple logistic regression analysis showed that male patients were 10.8 (CI: 2.6-45.2) times the odds than women to have an FEV (1) /FVC < 0.7, and non-atopic patients were 5.2 (CI: 1.3-20.3) times the odds to have an FEV (1) /FVC < 0.7 than atopic patients. We conclude that in patients with adult onset asthma, male gender and absence of atopy are associated with persistent airflow limitation. This might suggest that amongst patients with adult onset asthma, non-atopic male patients are at increased risk of accelerated decline in lung function. © 2012 Blackwell Publishing Ltd.

Cluster Analysis on Longitudinal Data of Patients with Adult-Onset Asthma.

PubMed

Ilmarinen, Pinja; Tuomisto, Leena E; Niemelä, Onni; Tommola, Minna; Haanpää, Jussi; Kankaanranta, Hannu

Previous cluster analyses on asthma are based on cross-sectional data. To identify phenotypes of adult-onset asthma by using data from baseline (diagnostic) and 12-year follow-up visits. The Seinäjoki Adult Asthma Study is a 12-year follow-up study of patients with new-onset adult asthma. K-means cluster analysis was performed by using variables from baseline and follow-up visits on 171 patients to identify phenotypes. Five clusters were identified. Patients in cluster 1 (n = 38) were predominantly nonatopic males with moderate smoking history at baseline. At follow-up, 40% of these patients had developed persistent obstruction but the number of patients with uncontrolled asthma (5%) and rhinitis (10%) was the lowest. Cluster 2 (n = 19) was characterized by older men with heavy smoking history, poor lung function, and persistent obstruction at baseline. At follow-up, these patients were mostly uncontrolled (84%) despite daily use of inhaled corticosteroid (ICS) with add-on therapy. Cluster 3 (n = 50) consisted mostly of nonsmoking females with good lung function at diagnosis/follow-up and well-controlled/partially controlled asthma at follow-up. Cluster 4 (n = 25) had obese and symptomatic patients at baseline/follow-up. At follow-up, these patients had several comorbidities (40% psychiatric disease) and were treated daily with ICS and add-on therapy. Patients in cluster 5 (n = 39) were mostly atopic and had the earliest onset of asthma, the highest blood eosinophils, and FEV 1 reversibility at diagnosis. At follow-up, these patients used the lowest ICS dose but 56% were well controlled. Results can be used to predict outcomes of patients with adult-onset asthma and to aid in development of personalized therapy (NCT02733016 at ClinicalTrials.gov). Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Increased prospective health service use for depression among adults with childhood onset bipolar disorder.

PubMed

Sala, Regina; Goldstein, Benjamin I; Wang, Shuai; Flórez-Salamanca, Ludwing; Iza, Miren; Blanco, Carlos

2013-11-01

To examine the prospective relationship between age of onset of bipolar disorder and the demographic and clinical characteristics, treatment, new onset of psychiatric comorbidity, and psychosocial functioning among adults with bipolar disorder. As part of the National Epidemiologic Survey on Alcohol and Related Conditions, 1600 adults who met lifetime Statistical Manual of Mental Disorders, 4th edition criteria for bipolar disorder-I (n = 1172) and bipolar disorder-II (n = 428) were included. Individuals were evaluated using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-IV version for Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and data were analyzed from Waves 1 and 2, approximately 3 years apart. Individuals with bipolar disorder were divided into three age at onset groups: childhood (<13 years old, n = 115), adolescence (13-18 years old, n = 396), and adulthood (>19 year old, n = 1017). After adjusting for confounding factors, adults with childhood-onset bipolar disorder were more likely to see a counselor, have been hospitalized, and have received emergency room treatment for depression compared with those with adulthood-onset bipolar disorder. By contrast, there were no differences in the severity of mania or hypomania, new onset of comorbidity, and psychosocial functioning by age of bipolar disorder onset. Childhood-onset bipolar disorder is prospectively associated with seeking treatment for depression, an important proxy for depressive severity. Longitudinal studies are needed in order to determine whether prompt identification, accurate diagnosis, and early intervention can serve to mitigate the burden of childhood onset on the long-term depressive burden of bipolar disorder. Copyright © 2013 Mosby, Inc. All rights reserved.

Adult-Onset Type 1 Diabetes: A Qualitative Study of Decision-Making Needs.

PubMed

Jull, Janet; Witteman, Holly O; Ferne, Judi; Yoganathan, Manosila; Stacey, Dawn

2016-04-01

Type 1 diabetes is an autoimmune disease resulting from insulin deficiency and must be carefully managed to prevent serious health complications. Diabetes education and management strategies usually focus on meeting the decision-making needs of children and their families, but little is known about the decisional needs of people with adult-onset type 1 diabetes. The aim of this study was to explore the diabetes-related decision-making needs of people diagnosed with adult-onset type 1 diabetes. An interpretive descriptive qualitative study was conducted. Participants who self-identified as having adult-onset type 1 diabetes were interviewed using a semistructured interview guide. Transcripts were coded to identify needs, supports and barriers using thematic analysis. Participating in the study were 8 adults (2 men, 6 women), ages 33 to 57, with type 1 diabetes for durations of 1 to 20 or more years. Their decision-making needs are summarized in 6 broad themes: 1) people diagnosed with type 1 diabetes are launched into a process of decision-making; 2) being diagnosed with type 1 diabetes means you will always have to make decisions; 3) knowledge is crucial; 4) personal preferences matter; 5) support is critical for decisions about self-care in type 1 diabetes; 6) living with type 1 diabetes means making very individualized decisions about daily life. The findings describe the sudden and ubiquitous nature of type 1 diabetes decision-making and the need to tailor approaches for making care decisions in type 1 diabetes. People diagnosed with adult-onset type 1 diabetes require access to reliable information, support and opportunities for participation in decision-making. Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

Psychiatric and Cognitive Phenotype of Childhood Myotonic Dystrophy Type 1

ERIC Educational Resources Information Center

Douniol, Marie; Jacquette, Aurelia; Cohen, David; Bodeau, Nicolas; Rachidi, Linda; Angeard, Nathalie; Cuisset, Jean-Marie; Vallee, Louis; Eymard, Bruno; Plaza, Monique; Heron, Delphine; Guile, Jean-Marc

2012-01-01

Aim: To investigate the psychiatric and cognitive phenotype in young individuals with the childhood form of myotonic dystrophy type 1 (DM1). Method: Twenty-eight individuals (15 females, 13 males) with childhood DM1 (mean age 17y, SD 4.6, range 7-24y) were assessed using standardized instruments and cognitive testing of general intelligence,…

The Evidence-Based Approach to Adult-Onset Idiopathic Nephrotic Syndrome

PubMed Central

Canetta, Pietro A. A.; Radhakrishnan, Jai

2015-01-01

Adult-onset nephrotic syndrome (NS) differs from its pediatric counterpart in several important ways. Most importantly, NS in adults is more etiologically heterogeneous compared to children, and thus treatment approaches rely heavily on the histological diagnosis provided by renal biopsy. The evidence-based approach to treatment of adult NS has been critically examined by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines in glomerulonephritis, published in 2012. Here, we examine the strengths and limits of those guidelines and review recent work that expands the evidence-based approach. PMID:26442238

Clinical features of adult-onset chronic active Epstein-Barr virus infection: a retrospective analysis.

PubMed

Arai, Ayako; Imadome, Ken-Ichi; Watanabe, Yuko; Yoshimori, Mayumi; Koyama, Takatoshi; Kawaguchi, Takeharu; Nakaseko, Chiaki; Fujiwara, Shigeyoshi; Miura, Osamu

2011-05-01

We performed a retrospective analysis of patients with adult-onset chronic active Epstein-Barr virus infection (CAEBV). First, we analyzed five patients (aged 28-72) diagnosed at our hospitals with EBV-infected clonally proliferating T cells. Four patients were administered cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) chemotherapy, but no remarkable decrease of viral load was observed in three of the patients. The other patient died 19 days after initiation of CHOP treatment due to disease progression. Addition of high-dose cytarabine to the regimens of two of the patients was discontinued shortly after administration, due to the development of grade 4 pericardial effusion. Together, these regimens may be insufficient for treating adult-onset CAEBV. We next reviewed 23 adult-onset CAEBV patients, adding 18 previously reported patients to the five patients described in the present study. T cells were frequently infected (87%), whereas NK- and T-cell types are known to be almost equally prevalent in childhood-onset cases. The time duration from the onset of disease to initiation of treatment averaged 20 months. Reports showed that 12 patients died; seven patients died at an average of 8 months after initiation of treatment. Patients' disease courses seemed to be rapidly progressive and more aggressive than those of childhood-onset cases. More cases must be studied to clarify clinical features and establish an optimal treatment strategy.

Responsiveness of performance-based outcome measures for mobility, balance, muscle strength and manual dexterity in adults with myotonic dystrophy type 1.

PubMed

Kierkegaard, Marie; Petitclerc, Émilie; Hébert, Luc J; Mathieu, Jean; Gagnon, Cynthia

2018-02-28

To assess changes and responsiveness in outcome measures of mobility, balance, muscle strength and manual dexterity in adults with myotonic dystrophy type 1. A 9-year longitudinal study conducted with 113 patients. The responsiveness of the Timed Up and Go test, Berg Balance Scale, quantitative muscle testing, grip and pinch-grip strength, and Purdue Pegboard Test was assessed using criterion and construct approaches. Patient-reported perceived changes (worse/stable) in balance, walking, lower-limb weakness, stair-climbing and hand weakness were used as criteria. Predefined hypotheses about expected area under the receiver operating characteristic curves (criterion approach) and correlations between relative changes (construct approach) were explored. The direction and magnitude of median changes in outcome measures corresponded with patient-reported changes. Median changes in the Timed Up and Go test, grip strength, pinch-grip strength and Purdue Pegboard Test did not, in general, exceed known measurement errors. Most criterion (72%) and construct (70%) approach hypotheses were supported. Promising responsiveness was found for outcome measures of mobility, balance and muscle strength. Grip strength and manual dexterity measures showed poorer responsiveness. The performance-based outcome measures captured changes over the 9-year period and responsiveness was promising. Knowledge of measurement errors is needed to interpret the meaning of these longitudinal changes.

Pediatric-Onset and Adult-Onset Separation Anxiety Disorder Across Countries in the World Mental Health Survey

PubMed Central

Silove, Derrick; Alonso, Jordi; Bromet, Evelyn; Gruber, Mike; Sampson, Nancy; Scott, Kate; Andrade, Laura; Benjet, Corina; de Almeida, Jose Miguel Caldas; De Girolamo, Giovanni; de Jonge, Peter; Demyttenaere, Koen; Fiestas, Fabian; Florescu, Silvia; Gureje, Oye; He, Yanling; Karam, Elie; Lepine, Jean-Pierre; Murphy, Sam; Villa-Posada, Jose; Zarkov, Zahari; Kessler, Ronald C.

2016-01-01

Objective The age-at-onset criterion for separation anxiety disorder was removed in DSM-5, making it timely to examine the epidemiology of separation anxiety disorder as a disorder with onsets spanning the life course, using cross-country data. Method The sample included 38,993 adults in 18 countries in the World Health Organization (WHO) World Mental Health Surveys. The WHO Composite International Diagnostic Interview was used to assess a range of DSM-IV disorders that included an expanded definition of separation anxiety disorder allowing onsets in adulthood. Analyses focused on prevalence, age at onset, comorbidity, predictors of onset and persistence, and separation anxiety-related role impairment. Results Lifetime separation anxiety disorder prevalence averaged 4.8% across countries (interquartile range [25th–75th percentiles]=1.4%–6.4%), with 43.1% of lifetime onsets occurring after age 18. Significant time-lagged associations were found between earlier separation anxiety disorder and subsequent onset of internalizing and externalizing DSM-IV disorders and conversely between these disorders and subsequent onset of separation anxiety disorder. Other consistently significant predictors of lifetime separation anxiety disorder included female gender, retrospectively reported childhood adversities, and lifetime traumatic events. These predictors were largely comparable for separation anxiety disorder onsets in childhood, adolescence, and adulthood and across country income groups. Twelve-month separation anxiety disorder prevalence was considerably lower than lifetime prevalence (1.0% of the total sample; interquartile range=0.2%–1.2%). Severe separation anxiety-related 12-month role impairment was significantly more common in the presence (42.4%) than absence (18.3%) of 12-month comorbidity. Conclusions Separation anxiety disorder is a common and highly comorbid disorder that can have onset across the lifespan. Childhood adversity and lifetime trauma are

Adult-onset Minimal Change Disease with IgA Nephropathy and Hepatitis C

PubMed Central

Chowdhury, Waliul; Saleem, Tahira Sabeen; Lodhi, Muhammad Uzair; Syed, Intekhab Askari; Iqbal, Hafiz Imran

2018-01-01

Minimal change disease (MCD) is one of the most common causes of nephrotic syndrome in children, leading to heavy proteinuria and edema. However, it is not as common in adults. Adult-onset minimal change disease with IgA nephropathy is rare. The initial presentation of heavy proteinuria and edema with effacement of podocytes on electron microscopy (EM) should lead the physician to suspect minimal change disease regardless of age. We present a 44-year-old male patient with a history of hepatitis C virus (HCV) who presented with sudden onset of lower extremity edema and 6.6 grams (g) of proteinuria per day. PMID:29682437

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

PubMed

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

2016-06-01

We evaluated the psychiatric comorbidities in adults who were diagnosed with Diagnostic and Statistical Manual of Mental disorders, 5th edition attention-deficit/hyperactivity disorder as a function of recalled symptom onset before and after the age of 7 years and whether the childhood attention-deficit/hyperactivity disorder symptoms were associated with psychiatric comorbidities. In all, 214 adults who were diagnosed with Diagnostic and Statistical Manual of Mental disorders, 5th edition attention-deficit/hyperactivity disorder and 174 non-attention-deficit/hyperactivity disorder controls (aged 17-40 years) received psychiatric interviews to confirm their previous and current attention-deficit/hyperactivity disorder status and other psychiatric diagnoses. Demographics and risks of lifetime psychiatric disorders were compared among three groups: (1) attention-deficit/hyperactivity disorder, onset <7 years (early-onset); (2) attention-deficit/hyperactivity disorder, onset between 7 and 12 years (late-onset) and (3) non-attention-deficit/hyperactivity disorder controls. We also tested the effects of attention-deficit/hyperactivity disorder symptoms on the risk of later psychiatric comorbidities by Cox regression analyses. Regardless of the age of onset, attention-deficit/hyperactivity disorder was significantly associated with a wide range of psychiatric comorbidities. There were similar comorbid patterns between early- and late-onset attention-deficit/hyperactivity disorder. Regardless of attention-deficit/hyperactivity disorder diagnosis, increased severity of attention-deficit/hyperactivity disorder symptoms was associated with higher risks of oppositional defiant disorder, conduct disorder, dysthymia and sleep disorder but not major depression, which was associated with the attention-deficit/hyperactivity disorder diagnosis. Our findings suggest that elevating the threshold of age of onset to 12 years in Diagnostic and Statistical Manual of Mental

Abnormalities in Skeletal Muscle Myogenesis, Growth, and Regeneration in Myotonic Dystrophy.

PubMed

André, Laurène M; Ausems, C Rosanne M; Wansink, Derick G; Wieringa, Bé

2018-01-01

Myotonic dystrophy type 1 (DM1) and 2 (DM2) are autosomal dominant degenerative neuromuscular disorders characterized by progressive skeletal muscle weakness, atrophy, and myotonia with progeroid features. Although both DM1 and DM2 are characterized by skeletal muscle dysfunction and also share other clinical features, the diseases differ in the muscle groups that are affected. In DM1, distal muscles are mainly affected, whereas in DM2 problems are mostly found in proximal muscles. In addition, manifestation in DM1 is generally more severe, with possible congenital or childhood-onset of disease and prominent CNS involvement. DM1 and DM2 are caused by expansion of (CTG•CAG)n and (CCTG•CAGG)n repeats in the 3' non-coding region of DMPK and in intron 1 of CNBP , respectively, and in overlapping antisense genes. This critical review will focus on the pleiotropic problems that occur during development, growth, regeneration, and aging of skeletal muscle in patients who inherited these expansions. The current best-accepted idea is that most muscle symptoms can be explained by pathomechanistic effects of repeat expansion on RNA-mediated pathways. However, aberrations in DNA replication and transcription of the DM loci or in protein translation and proteome homeostasis could also affect the control of proliferation and differentiation of muscle progenitor cells or the maintenance and physiological integrity of muscle fibers during a patient's lifetime. Here, we will discuss these molecular and cellular processes and summarize current knowledge about the role of embryonic and adult muscle-resident stem cells in growth, homeostasis, regeneration, and premature aging of healthy and diseased muscle tissue. Of particular interest is that also progenitor cells from extramuscular sources, such as pericytes and mesoangioblasts, can participate in myogenic differentiation. We will examine the potential of all these types of cells in the application of regenerative medicine for

Abnormalities in Skeletal Muscle Myogenesis, Growth, and Regeneration in Myotonic Dystrophy

PubMed Central

André, Laurène M.; Ausems, C. Rosanne M.; Wansink, Derick G.; Wieringa, Bé

2018-01-01

Myotonic dystrophy type 1 (DM1) and 2 (DM2) are autosomal dominant degenerative neuromuscular disorders characterized by progressive skeletal muscle weakness, atrophy, and myotonia with progeroid features. Although both DM1 and DM2 are characterized by skeletal muscle dysfunction and also share other clinical features, the diseases differ in the muscle groups that are affected. In DM1, distal muscles are mainly affected, whereas in DM2 problems are mostly found in proximal muscles. In addition, manifestation in DM1 is generally more severe, with possible congenital or childhood-onset of disease and prominent CNS involvement. DM1 and DM2 are caused by expansion of (CTG•CAG)n and (CCTG•CAGG)n repeats in the 3′ non-coding region of DMPK and in intron 1 of CNBP, respectively, and in overlapping antisense genes. This critical review will focus on the pleiotropic problems that occur during development, growth, regeneration, and aging of skeletal muscle in patients who inherited these expansions. The current best-accepted idea is that most muscle symptoms can be explained by pathomechanistic effects of repeat expansion on RNA-mediated pathways. However, aberrations in DNA replication and transcription of the DM loci or in protein translation and proteome homeostasis could also affect the control of proliferation and differentiation of muscle progenitor cells or the maintenance and physiological integrity of muscle fibers during a patient’s lifetime. Here, we will discuss these molecular and cellular processes and summarize current knowledge about the role of embryonic and adult muscle-resident stem cells in growth, homeostasis, regeneration, and premature aging of healthy and diseased muscle tissue. Of particular interest is that also progenitor cells from extramuscular sources, such as pericytes and mesoangioblasts, can participate in myogenic differentiation. We will examine the potential of all these types of cells in the application of regenerative medicine

Immortalized human myotonic dystrophy muscle cell lines to assess therapeutic compounds.

PubMed

Arandel, Ludovic; Polay Espinoza, Micaela; Matloka, Magdalena; Bazinet, Audrey; De Dea Diniz, Damily; Naouar, Naïra; Rau, Frédérique; Jollet, Arnaud; Edom-Vovard, Frédérique; Mamchaoui, Kamel; Tarnopolsky, Mark; Puymirat, Jack; Battail, Christophe; Boland, Anne; Deleuze, Jean-Francois; Mouly, Vincent; Klein, Arnaud F; Furling, Denis

2017-04-01

Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are autosomal dominant neuromuscular diseases caused by microsatellite expansions and belong to the family of RNA-dominant disorders. Availability of cellular models in which the DM mutation is expressed within its natural context is essential to facilitate efforts to identify new therapeutic compounds. Here, we generated immortalized DM1 and DM2 human muscle cell lines that display nuclear RNA aggregates of expanded repeats, a hallmark of myotonic dystrophy. Selected clones of DM1 and DM2 immortalized myoblasts behave as parental primary myoblasts with a reduced fusion capacity of immortalized DM1 myoblasts when compared with control and DM2 cells. Alternative splicing defects were observed in differentiated DM1 muscle cell lines, but not in DM2 lines. Splicing alterations did not result from differentiation delay because similar changes were found in immortalized DM1 transdifferentiated fibroblasts in which myogenic differentiation has been forced by overexpression of MYOD1. As a proof-of-concept, we show that antisense approaches alleviate disease-associated defects, and an RNA-seq analysis confirmed that the vast majority of mis-spliced events in immortalized DM1 muscle cells were affected by antisense treatment, with half of them significantly rescued in treated DM1 cells. Immortalized DM1 muscle cell lines displaying characteristic disease-associated molecular features such as nuclear RNA aggregates and splicing defects can be used as robust readouts for the screening of therapeutic compounds. Therefore, immortalized DM1 and DM2 muscle cell lines represent new models and tools to investigate molecular pathophysiological mechanisms and evaluate the in vitro effects of compounds on RNA toxicity associated with myotonic dystrophy mutations. © 2017. Published by The Company of Biologists Ltd.

Immortalized human myotonic dystrophy muscle cell lines to assess therapeutic compounds

PubMed Central

Arandel, Ludovic; Polay Espinoza, Micaela; Matloka, Magdalena; Bazinet, Audrey; De Dea Diniz, Damily; Naouar, Naïra; Rau, Frédérique; Jollet, Arnaud; Edom-Vovard, Frédérique; Mamchaoui, Kamel; Tarnopolsky, Mark; Puymirat, Jack; Battail, Christophe; Boland, Anne; Deleuze, Jean-Francois; Mouly, Vincent; Klein, Arnaud F.

2017-01-01

ABSTRACT Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are autosomal dominant neuromuscular diseases caused by microsatellite expansions and belong to the family of RNA-dominant disorders. Availability of cellular models in which the DM mutation is expressed within its natural context is essential to facilitate efforts to identify new therapeutic compounds. Here, we generated immortalized DM1 and DM2 human muscle cell lines that display nuclear RNA aggregates of expanded repeats, a hallmark of myotonic dystrophy. Selected clones of DM1 and DM2 immortalized myoblasts behave as parental primary myoblasts with a reduced fusion capacity of immortalized DM1 myoblasts when compared with control and DM2 cells. Alternative splicing defects were observed in differentiated DM1 muscle cell lines, but not in DM2 lines. Splicing alterations did not result from differentiation delay because similar changes were found in immortalized DM1 transdifferentiated fibroblasts in which myogenic differentiation has been forced by overexpression of MYOD1. As a proof-of-concept, we show that antisense approaches alleviate disease-associated defects, and an RNA-seq analysis confirmed that the vast majority of mis-spliced events in immortalized DM1 muscle cells were affected by antisense treatment, with half of them significantly rescued in treated DM1 cells. Immortalized DM1 muscle cell lines displaying characteristic disease-associated molecular features such as nuclear RNA aggregates and splicing defects can be used as robust readouts for the screening of therapeutic compounds. Therefore, immortalized DM1 and DM2 muscle cell lines represent new models and tools to investigate molecular pathophysiological mechanisms and evaluate the in vitro effects of compounds on RNA toxicity associated with myotonic dystrophy mutations. PMID:28188264

Gastrobronchial fistula following minimally invasive esophagectomy for esophageal cancer in a patient with myotonic dystrophy: Case report

PubMed Central

Hugin, Silje; Johnson, Egil; Johannessen, Hans-Olaf; Hofstad, Bjørn; Olafsen, Kjell; Mellem, Harald

2015-01-01

Introduction Myotonic dystrophies are inherited multisystemic diseases characterized by musculopathy, cardiac arrythmias and cognitive disorders. These patients are at increased risk for fatal post-surgical complications from pulmonary hypoventilation. We present a case with myotonic dystrophy and esophageal cancer who had a minimally invasive esophagectomy complicated with gastrobronchial fistulisation. Presentation of case A 44-year-old male with myotonic dystrophy type 1 and esophageal cancer had a minimally invasive esophagectomy performed instead of open surgery in order to reduce the risk for pulmonary complications. At day 15 respiratory failure occurred from a gastrobronchial fistula between the right intermediary bronchus (defect 7–8 mm) and the esophagogastric anastomosis (defect 10 mm). In order to minimize large leakage of air into the gastric conduit the anastomosis was stented and ventilation maintained at low airway pressures. His general condition improved and allowed extubation at day 29 and stent removal at day 35. Bronchoscopy confirmed that the fistula was healed. The patient was discharged from hospital at day 37 without further complications. Discussion The fistula was probably caused by bronchial necrosis from thermal injury during close dissection using the Ligasure instrument. Fistula treatment by non-surgical intervention was considered safer than surgery which could be followed by potentially life-threatening respiratory complications. Indications for stenting of gastrobronchial fistulas will be discussed. Conclusions Minimally invasive esophagectomy was performed instead of open surgery in a myotonic dystrophy patient as these patients are particularly vulnerable to respiratory complications. Gastrobronchial fistula, a major complication, was safely treated by stenting and low airway pressure ventilation. PMID:26520033

Adult onset Niemann-Pick type C disease: A clinical, neuroimaging and molecular genetic study.

PubMed

Battisti, Carla; Tarugi, Patrizla; Dotti, Maria Teresa; De Stefano, Nicola; Vattimo, Angelo; Chierichetti, Francesea; Calandra, Sebastiano; Federico, Antonio

2003-11-01

We report on a patient with adult-onset Niemann-Pick type C (NPC) disease, carrying the mutations P1007 and I1061T in the NPC1 gene, presenting with marked psychiatric changes followed by dystonia and cognitive impairment. Filipin staining, single photon emission computed tomography perfusional, positron emission tomography metabolic, conventional magnetic resonance imaging, and magnetic resonance spectroscopy findings suggested a pathophysiological correlation with phenotype expression. This case expands the clinical and genetic spectrum of the rare adult-onset NPC disease phenotype.

Congenital myotonic myopathy in the miniature schnauzer: an autosomal recessive trait.

PubMed

Vite, C H; Melniczek, J; Patterson, D; Giger, U

1999-01-01

Myotonia is a clinical sign characterized by a delay in skeletal muscle relaxation following electrical or mechanical stimulation. A series of related miniature schnauzer dogs with congenital myotonic myopathy were studied. A composite pedigree of six affected litters and the results of a planned breeding between two affected animals are consistent with an autosomal recessive mode of inheritance.

PubMed Central

MEOLA, GIOVANNI

2013-01-01

Myotonic dystrophy (DM) is the most common adult muscular dystrophy, characterized by autosomal dominant progressive myopathy, myotonia and multiorgan involvement. To date two distinct forms caused by similar mutations have been identified. Myotonic dystrophy type 1 (DM1, Steinert's disease) was described more than 100 years ago and is caused by a (CTG)n expansion in DMPK, while myotonic dystrophy type 2 (DM2) was identified only 18 years ago and is caused by a (CCTG)n expansion in ZNF9/CNBP. When transcribed into CUG/CCUG-containing RNA, mutant transcripts aggregate as nuclear foci that sequester RNA-binding proteins, resulting in spliceopathy of downstream effector genes. Despite clinical and genetic similarities, DM1 and DM2 are distinct disorders requiring different diagnostic and management strategies. DM1 may present in four different forms: congenital, early childhood, adult onset and late-onset oligosymptomatic DM1. Congenital DM1 is the most severe form of DM characterized by extreme muscle weakness and mental retardation. In DM2 the clinical phenotype is extremely variable and there are no distinct clinical subgroups. Congenital and childhood-onset forms are not present in DM2 and, in contrast to DM1, myotonia may be absent even on EMG. Due to the lack of awareness of the disease among clinicians, DM2 remains largely underdiagnosed. The delay in receiving the correct diagnosis after onset of first symptoms is very long in DM: on average more than 5 years for DM1 and more than 14 years for DM2 patients. The long delay in the diagnosis of DM causes unnecessary problems for the patients to manage their lives and anguish with uncertainty of prognosis and treatment. PMID:24803843

Adult-onset tic disorder, motor stereotypies, and behavioural disturbance associated with antibasal ganglia antibodies.

PubMed

Edwards, Mark J; Dale, Russell C; Church, Andrew J; Trikouli, Eleni; Quinn, Niall P; Lees, Andrew J; Giovannoni, Gavin; Bhatia, Kailash P

2004-10-01

The onset of tics in adulthood is rare and, unlike the childhood variety, there is commonly a secondary environmental cause. We present four cases (1 man, 3 women) with an adult onset tic disorder (mean age of onset, 36 years; range, 27-42 years) associated with the presence of serum antibasal ganglia antibodies (ABGA). One patient had motor tics and unusual motor stereotypies, 2 had multiple motor and vocal tics, and the remaining patient had motor tics only. Concomitant psychiatric disturbance was noted in 3 cases. In 2 cases, there was a close temporal relationship between upper respiratory tract infection and the subsequent onset of tics. Imaging was possible in three cases and was normal in two but revealed a lesion involving the right caudate and lentiform nuclei in the other. We suggest that there might be a causal relationship between ABGA and the clinical syndrome in these cases and that ABGA should be considered as a possible etiology for adult-onset tics. (c) 2004 Movement Disorder Society.

Adult-onset Still's disease initially thought to be an odontogenic infection: A case report.

PubMed

Hino, Shunsuke; Nakamura, Satoshi; Kaneko, Takahiro; Horie, Norio; Shimoyama, Tetsuo

2018-06-01

To present a case of Adult-onset Still's disease (AOSD) initially suspected to be odontogenic inflammation. Adult-onset Still's disease is a rare, complex autoinflammatory disease and a known cause of fever of unknown origin. The patient had both a fever and dental pain. Following meticulous examination, the patient was diagnosed with AOSD. Clinicians should keep in mind that a patient such as AOSD may visit their clinics. © 2018 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd.

RANDOMISED ASPIRIN ASSIGNMENT AND RISK OF ADULT-ONSET ASTHMA IN THE WOMEN'S HEALTH STUDY

PubMed Central

Kurth, Tobias; Barr, R. Graham; Gaziano, J. Michael; Buring, Julie E.

2008-01-01

Rationale Randomised data in men showed a small but significant reduction in risk of adult-onset asthma among those assigned to aspirin. Results from an observational study in women suggest that frequent use of aspirin decreased the risk of adult-onset asthma. Randomised data in women are lacking. Objective To test the effect of 100 mg of aspirin on alternate days or placebo on the risk of adult-onset asthma in the Women's Health Study. Methods Post-hoc analyses from a randomised, double-blind, placebo-controlled clinical trial of aspirin and vitamin E in apparently healthy US women with no indication or contraindication to aspirin therapy and free of a history of asthma at study entry. Measurements Female health professionals could self-report an asthma diagnosis on yearly questionnaires. Results Among 37,270 women without reported history of asthma prior to randomisation and during 10 years of follow-up, there were 872 new reports of asthma diagnosis in the aspirin group and 963 in the placebo group (hazard ratio=0.90; 95% confidence interval=0.82−0.99; P=0.027). This apparent 10% lower relative risk of incident adult-onset asthma among those assigned to aspirin was significantly modified by body mass index, indicating no effect among women with a body mass index of ≥30 kg/m2. There was no significant effect modification by age, smoking status, exercise levels, postmenopausal hormone use, or randomised vitamin E assignment. Conclusions In this large, randomised clinical trial of apparently healthy adult women, assignment of 100 mg of aspirin on alternate days reduced the relative risk of newly reported diagnosis of asthma. PMID:18339679

Dioxin (TCDD) Induces Epigenetic Transgenerational Inheritance of Adult Onset Disease and Sperm Epimutations

PubMed Central

Manikkam, Mohan; Tracey, Rebecca; Guerrero-Bosagna, Carlos; Skinner, Michael K.

2012-01-01

Environmental compounds can promote epigenetic transgenerational inheritance of adult-onset disease in subsequent generations following ancestral exposure during fetal gonadal sex determination. The current study examined the ability of dioxin (2,3,7,8-tetrachlorodibenzo[p]dioxin, TCDD) to promote epigenetic transgenerational inheritance of disease and DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to dioxin during fetal day 8 to 14 and adult-onset disease was evaluated in F1 and F3 generation rats. The incidences of total disease and multiple disease increased in F1 and F3 generations. Prostate disease, ovarian primordial follicle loss and polycystic ovary disease were increased in F1 generation dioxin lineage. Kidney disease in males, pubertal abnormalities in females, ovarian primordial follicle loss and polycystic ovary disease were increased in F3 generation dioxin lineage animals. Analysis of the F3 generation sperm epigenome identified 50 differentially DNA methylated regions (DMR) in gene promoters. These DMR provide potential epigenetic biomarkers for transgenerational disease and ancestral environmental exposures. Observations demonstrate dioxin exposure of a gestating female promotes epigenetic transgenerational inheritance of adult onset disease and sperm epimutations. PMID:23049995

Differences in Long-Term Disease Activity and Treatment of Adult Patients With Childhood-and Adult-Onset Systemic Lupus Erythematosus

PubMed Central

Hersh, Aimee O.; von Scheven, Emily; Yazdany, Jinoos; Panopalis, Pantelis; Trupin, Laura; Julian, Laura; Katz, Patricia; Criswell, Lindsey A.; Yelin, Edward

2009-01-01

Objective To compare differences in long-term outcome between adults with childhood-onset (age at diagnosis <18 years) systemic lupus erythematosus (SLE) and with adult-onset SLE. Methods Data were derived from the University of California Lupus Outcomes Study, a longitudinal cohort of 885 adult subjects with SLE (90 childhood-onset [cSLE], 795 adult-onset [aSLE]). Baseline and 1-year followup data were obtained via structured 1-hour telephone interviews conducted between 2002 and 2006. Using self-report data, differences in organ involvement and disease morbidity, current disease status and activity, past and current medication use, and number of physician visits were compared, based on age at diagnosis of SLE. Results Average disease duration for the cSLE and aSLE subgroups was 16.5 and 13.4 years, respectively, and mean age at followup was 30.5 and 49.9 years, respectively. When compared with aSLE subjects, cSLE subjects had a higher frequency of SLE-related renal disease, whereas aSLE subjects were more likely to report a history of pulmonary disease. Rates of clotting disorders, seizures, and myocardial infarction were similar between the 2 groups. At followup, cSLE subjects had lower overall disease activity, but were more likely to be taking steroids and other immunosuppressive therapies. The total number of yearly physician visits was similar between the 2 groups, although cSLE subjects had a higher number of nephrology visits. Conclusion This study demonstrates important differences in the outcomes of patients with cSLE and aSLE, and provides important prognostic information about long-term SLE disease activity and treatment. PMID:19116979

Obesity and onset of depression among U.S. middle-aged and older adults.

PubMed

Xiang, Xiaoling; An, Ruopeng

2015-03-01

This paper aims to examine the relationship between obesity and onset of depression among U.S. middle-aged and older adults. Data came from 1994 to 2010 waves of the Health and Retirement Study. Study sample consisted of 6514 community-dwelling adults born between 1931 and 1941 who were free of clinically relevant depressive symptoms in 1994. Body mass index (BMI) was calculated from self-reported height/weight. Body weight status was classified into normal weight (18.5kg/m(2)≤BMI<25kg/m(2)), overweight (25kg/m(2)≤BMI<30kg/m(2)), and obesity (BMI≥30kg/m(2)). A score of ≥3 on the 8-item Center for Epidemiologic Studies Depression Scale was used to define clinically relevant depressive symptoms. Kaplan-Meier estimator and time-dependent Cox proportional hazards model were performed to examine the association between body weight status and onset of clinically relevant depressive symptoms. Unhealthy body weight was associated future onset of depression. Compared with their normal weight counterparts, overweight and obese participants were 13% (hazard ratio [HR]=1.13, 95% confidence interval [CI]=1.04-1.23) and 9% (HR=1.09, 95% CI=1.01-1.18) more likely to have onset of clinically relevant depressive symptoms during the 16years of follow-up, respectively. The relationship between obesity and depression onset appeared stronger among females and non-Hispanic whites than their male and racial/ethnic minority counterparts. Health care providers should be aware of the potential risk for depression among obese older adults. Copyright © 2014 Elsevier Inc. All rights reserved.

Clinical Value of NPHS2 Analysis in Early- and Adult-Onset Steroid-Resistant Nephrotic Syndrome

PubMed Central

Santín, Sheila; Tazón-Vega, Bárbara; Silva, Irene; Cobo, María Ángeles; Giménez, Isabel; Ruíz, Patricia; García-Maset, Rafael; Ballarín, José

2011-01-01

Summary Background and objectives To date, very few cases with adult-onset focal segmental glomerulosclerosis (FSGS) carrying NPHS2 variants have been described, all of them being compound heterozygous for the p.R229Q variant and one pathogenic mutation. Design, setting, participants, & measurements Mutation analysis was performed in 148 unrelated Spanish patients, of whom 50 presented with FSGS after 18 years of age. Pathogenicity of amino acid substitutions was evaluated through an in silico scoring system. Haplotype analysis was carried out using NPHS2 single nucleotide polymorphism and microsatellite markers. Results Compound heterozygous or homozygous NPHS2 pathogenic mutations were identified in seven childhood-onset steroid-resistant nephrotic syndrome (SRNS) cases. Six additional cases with late childhood- and adult-onset SRNS were compound heterozygotes for p.R229Q and one pathogenic mutation, mostly p.A284V. p.R229Q was more frequent among SRNS cases relative to controls (odds ratio = 2.65; P = 0.02). Significantly higher age at onset of the disease and slower progression to ESRD were found in patients with one pathogenic mutation plus the p.R229Q variant in respect to patients with two NPHS2 pathogenic mutations. Conclusions NPHS2 analysis has a clinical value in both childhood- and adult-onset SRNS patients. For adult-onset patients, the first step should be screening for p.R229Q and, if positive, for p.A284V. These alleles are present in conserved haplotypes, suggesting a common origin for these substitutions. Patients carrying this specific NPHS2 allele combination did not respond to corticoids or immunosuppressors and showed FSGS, average 8-year progression to ESRD, and low risk for recurrence of FSGS after kidney transplant. PMID:20947785

Clinicopathological Analysis of Glomerular Disease of Adult Onset Nephrotic Syndrome in an Indian Cohort- A Retrospective Study

PubMed Central

Suryawanshi, Mayur; Karnik, Swapnil

2017-01-01

Introduction Primary glomerular disease presenting with adult onset nephrotic syndrome are a major cause of chronic renal failure worldwide. The spectrum of renal disease presenting with nephrotic syndrome has undergone a gradual change globally over the course of time. However, there still exist regional differences in the incidence of primary glomerular diseases causing adult onset nephrotic syndrome. Aim To observe the spectrum of renal diseases presenting with adult onset nephrotic syndrome with comparative analysis of changing trends over the last five decades with regards to Western and Indian literature. Materials and Methods Subjects included patients with age of 18-80 years presenting with nephrotic syndrome. Renal biopsies with immunofluoroscence studies were performed in all patients. Baseline clinical parameters of serum urea, creatinine, albumin, globulin, cholesterol, 24 hour urine protein and urine microscopy were recorded. Descriptive statistics was used and results were expressed as frequencies, percentages, and mean±standard deviation. Results A total of 227 patients (72% males) were included for the study. Primary glomerular diseases formed 74.01% of total cases and majority of patients included males in the 4th decade. Minimal Change Disease (MCD) (15.8%) including its variants was the most common primary glomerular disease for adult onset of nephrotic syndrome followed by Mesangial proliferative Glomerulonephritis (MSGN) (13.2%). Membranous nephropathy and Type I Membranoproliferative Glomerulonephritis (MPGN) individually accounted for 12.3% of patients. Focal and Segmental Glomerulosclerosis (FSGS) accounted for only 11% of patients. Although, increased incidence of FSGS has been observed worldwide, there exist important regional differences in primary glomerular diseases in Indian population. MCD remains a major glomerular disease for adult onset nephrotic syndrome in different parts of India. Conclusion Our study over three years

Evolution of disease phenotype in adult and pediatric onset Crohn’s disease in a population-based cohort

PubMed Central

Lovasz, Barbara Dorottya; Lakatos, Laszlo; Horvath, Agnes; Szita, Istvan; Pandur, Tunde; Mandel, Michael; Vegh, Zsuzsanna; Golovics, Petra Anna; Mester, Gabor; Balogh, Mihaly; Molnar, Csaba; Komaromi, Erzsebet; Kiss, Lajos Sandor; Lakatos, Peter Laszlo

2013-01-01

AIM: To investigate the evolution of disease phenotype in adult and pediatric onset Crohn’s disease (CD) populations, diagnosed between 1977 and 2008. METHODS: Data of 506 incident CD patients were analyzed (age at diagnosis: 28.5 years, interquartile range: 22-38 years). Both in- and outpatient records were collected prospectively with a complete clinical follow-up and comprehensively reviewed in the population-based Veszprem province database, which included incident patients diagnosed between January 1, 1977 and December 31, 2008 in adult and pediatric onset CD populations. Disease phenotype according to the Montreal classification and long-term disease course was analysed according to the age at onset in time-dependent univariate and multivariate analysis. RESULTS: Among this population-based cohort, seventy-four (12.8%) pediatric-onset CD patients were identified (diagnosed ≤ 17 years of age). There was no significant difference in the distribution of disease behavior between pediatric (B1: 62%, B2: 15%, B3: 23%) and adult-onset CD patients (B1: 56%, B2: 21%, B3: 23%) at diagnosis, or during follow-up. Overall, the probability of developing complicated disease behaviour was 49.7% and 61.3% in the pediatric and 55.1% and 62.4% in the adult onset patients after 5- and 10-years of follow-up. Similarly, time to change in disease behaviour from non stricturing, non penetrating (B1) to complicated, stricturing or penetrating (B2/B3) disease was not significantly different between pediatric and adult onset CD in a Kaplan-Meier analysis. Calendar year of diagnosis (P = 0.04), ileal location (P < 0.001), perianal disease (P < 0.001), smoking (P = 0.038) and need for steroids (P < 0.001) were associated with presence of, or progression to, complicated disease behavior at diagnosis and during follow-up. A change in disease location was observed in 8.9% of patients and it was associated with smoking status (P = 0.01), but not with age at diagnosis. CONCLUSION: Long

French translation and cross-cultural adaptation of The Myotonic Dystrophy Health Index.

PubMed

Gagnon, Cynthia; Tremblay, Marjolaine; CôTé, Isabelle; Heatwole, Chad

2018-04-01

Validation studies of disease-specific instruments for myotonic dystrophy type-1 (DM1) are required prior to their global use in clinical trials involving different cultures and countries. Here we translate and culturally adapt the Myotonic Dystrophy Health Index (MDHI), a disease-specific patient-reported outcome (PRO) measure, for a French DM1 population. Using the International Society for Pharmacoeconomics and Outcomes Research Task Force method for translation and adaptation of PRO questionnaires, we created a French translation of the MDHI. We subsequently tested this instrument in a cohort of French-speaking patients with DM1. The MDHI was forward and back translated and modified by consensus to create the most compatible translation. Cognitive interviews were conducted with 5 patients with DM1 to ensure the usability and understanding of the translation. The French version of the MDHI is an optimal translation of the original instrument that is acceptable to native patients and ready for clinical trial use. Muscle Nerve 57: 686-689, 2018. © 2017 Wiley Periodicals, Inc.

Distinguishing adult-onset asthma from COPD: a review and a new approach

PubMed Central

Abramson, Michael J; Perret, Jennifer L; Dharmage, Shyamali C; McDonald, Vanessa M; McDonald, Christine F

2014-01-01

Adult-onset asthma and chronic obstructive pulmonary disease (COPD) are major public health burdens. This review presents a comprehensive synopsis of their epidemiology, pathophysiology, and clinical presentations; describes how they can be distinguished; and considers both established and proposed new approaches to their management. Both adult-onset asthma and COPD are complex diseases arising from gene–environment interactions. Early life exposures such as childhood infections, smoke, obesity, and allergy influence adult-onset asthma. While the established environmental risk factors for COPD are adult tobacco and biomass smoke, there is emerging evidence that some childhood exposures such as maternal smoking and infections may cause COPD. Asthma has been characterized predominantly by Type 2 helper T cell (Th2) cytokine-mediated eosinophilic airway inflammation associated with airway hyperresponsiveness. In established COPD, the inflammatory cell infiltrate in small airways comprises predominantly neutrophils and cytotoxic T cells (CD8 positive lymphocytes). Parenchymal destruction (emphysema) in COPD is associated with loss of lung tissue elasticity, and small airways collapse during exhalation. The precise definition of chronic airflow limitation is affected by age; a fixed cut-off of forced expiratory volume in 1 second/forced vital capacity leads to overdiagnosis of COPD in the elderly. Traditional approaches to distinguishing between asthma and COPD have highlighted age of onset, variability of symptoms, reversibility of airflow limitation, and atopy. Each of these is associated with error due to overlap and convergence of clinical characteristics. The management of chronic stable asthma and COPD is similarly convergent. New approaches to the management of obstructive airway diseases in adults have been proposed based on inflammometry and also multidimensional assessment, which focuses on the four domains of the airways, comorbidity, self-management, and

Gender as a Modifying Factor Influencing Myotonic Dystrophy Type 1 Phenotype Severity and Mortality: A Nationwide Multiple Databases Cross-Sectional Observational Study.

PubMed

Dogan, Celine; De Antonio, Marie; Hamroun, Dalil; Varet, Hugo; Fabbro, Marianne; Rougier, Felix; Amarof, Khadija; Arne Bes, Marie-Christine; Bedat-Millet, Anne-Laure; Behin, Anthony; Bellance, Remi; Bouhour, Françoise; Boutte, Celia; Boyer, François; Campana-Salort, Emmanuelle; Chapon, Françoise; Cintas, Pascal; Desnuelle, Claude; Deschamps, Romain; Drouin-Garraud, Valerie; Ferrer, Xavier; Gervais-Bernard, Helene; Ghorab, Karima; Laforet, Pascal; Magot, Armelle; Magy, Laurent; Menard, Dominique; Minot, Marie-Christine; Nadaj-Pakleza, Aleksandra; Pellieux, Sybille; Pereon, Yann; Preudhomme, Marguerite; Pouget, Jean; Sacconi, Sabrina; Sole, Guilhem; Stojkovich, Tanya; Tiffreau, Vincent; Urtizberea, Andoni; Vial, Christophe; Zagnoli, Fabien; Caranhac, Gilbert; Bourlier, Claude; Riviere, Gerard; Geille, Alain; Gherardi, Romain K; Eymard, Bruno; Puymirat, Jack; Katsahian, Sandrine; Bassez, Guillaume

2016-01-01

Myotonic Dystrophy type 1 (DM1) is one of the most heterogeneous hereditary disease in terms of age of onset, clinical manifestations, and severity, challenging both medical management and clinical trials. The CTG expansion size is the main factor determining the age of onset although no factor can finely predict phenotype and prognosis. Differences between males and females have not been specifically reported. Our aim is to study gender impact on DM1 phenotype and severity. We first performed cross-sectional analysis of main multiorgan clinical parameters in 1409 adult DM1 patients (>18 y) from the DM-Scope nationwide registry and observed different patterns in males and females. Then, we assessed gender impact on social and economic domains using the AFM-Téléthon DM1 survey (n = 970), and morbidity and mortality using the French National Health Service Database (n = 3301). Men more frequently had (1) severe muscular disability with marked myotonia, muscle weakness, cardiac, and respiratory involvement; (2) developmental abnormalities with facial dysmorphism and cognitive impairment inferred from low educational levels and work in specialized environments; and (3) lonely life. Alternatively, women more frequently had cataracts, dysphagia, digestive tract dysfunction, incontinence, thyroid disorder and obesity. Most differences were out of proportion to those observed in the general population. Compared to women, males were more affected in their social and economic life. In addition, they were more frequently hospitalized for cardiac problems, and had a higher mortality rate. Gender is a previously unrecognized factor influencing DM1 clinical profile and severity of the disease, with worse socio-economic consequences of the disease and higher morbidity and mortality in males. Gender should be considered in the design of both stratified medical management and clinical trials.

Genetics Home Reference: adult-onset leukoencephalopathy with axonal spheroids and pigmented glia

MedlinePlus

... it causes a severe decline in thinking and reasoning abilities (dementia). Over time, motor skills are affected, ... Schmahmann JD. Adult onset leukodystrophy with neuroaxonal spheroids: clinical, neuroimaging and neuropathologic observations. Brain Pathol. 2009 Jan; ...

[Sleep and respiratory disorders in myotonic dystrophy of Steinert].

PubMed

López-Esteban, P; Peraita-Adrados, R

2000-03-01

It has been hypothesized that hypersomnia and sleep related respiratory impairment are both central in origin in myotonic dystrophy. To describe by means of video-polysomnographic recordings the central origin of the sleep respiratory disorders. We studied 11 patients, 6 men and 5 women (mean age 42.7 years) with myotonic dystrophy. A moderate to severe ventilatory impairment of a primarily restrictive type was seen in all patients, three of them after the first episode of respiratory insufficiency. The patients were evaluated in order to determine their body mass index and presence of sleep-related complaints. Video-polysomnographic recordings (EEG, EOG, EKG, submental and tibialis anterior EMGs, respiration and Sa02) and pulmonary function tests were performed in each patient. Identical recordings were repeated in six cases, which were to undergo non-invasive bi-level ventilation (BiPAP) in order to adjust the inspiratory and expiratory pressures and the machine mode. We found slight hypopnea and apnea, predominantly of a central type, in stage 1 and REM sleep and alveolar hypoventilation in all patients. Sleep was disrupted and the efficiency index was very low. In three patients HLA typing showed a positive DQ6 haplotype. Six patients were treated with n-BiPAP. Nasal-BIPAP should be considered as an alternative in ventilatory support during sleep in these patients and video-polysomnography as a valid method of evaluating the ideal time to start treatment.

Mapping a gene for adult-onset primary open-angle glaucoma to chromosome 3q

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wirtz, M.K.; Samples, J.R.; Kramer, P.L.

1997-02-01

Glaucoma is the third-leading cause of blindness in the world, affecting >13.5 million people. Adult-on-set primary open-angle glaucoma (POAG) is the most common form of glaucoma in the United States. We present a family in which adult-onset POAG is inherited as an autosomal dominant trait. Twelve affected family members were identified from 44 at-risk individuals. The disease-causing gene was mapped to chromosome 3q21-24, with analysis of recombinant haplotypes suggesting a total inclusion region of 11.1 cM between markers D3S3637 and D3S1744. This is the first report of mapping of an adult-onset POAG gene to chromosome 3q, gene symbol GLC1C. 57more » refs., 3 figs., 3 tabs.« less

Abnormal splicing switch of DMD's penultimate exon compromises muscle fibre maintenance in myotonic dystrophy.

PubMed

Rau, Frédérique; Lainé, Jeanne; Ramanoudjame, Laetitita; Ferry, Arnaud; Arandel, Ludovic; Delalande, Olivier; Jollet, Arnaud; Dingli, Florent; Lee, Kuang-Yung; Peccate, Cécile; Lorain, Stéphanie; Kabashi, Edor; Athanasopoulos, Takis; Koo, Taeyoung; Loew, Damarys; Swanson, Maurice S; Le Rumeur, Elisabeth; Dickson, George; Allamand, Valérie; Marie, Joëlle; Furling, Denis

2015-05-28

Myotonic Dystrophy type 1 (DM1) is a dominant neuromuscular disease caused by nuclear-retained RNAs containing expanded CUG repeats. These toxic RNAs alter the activities of RNA splicing factors resulting in alternative splicing misregulation and muscular dysfunction. Here we show that the abnormal splicing of DMD exon 78 found in dystrophic muscles of DM1 patients is due to the functional loss of MBNL1 and leads to the re-expression of an embryonic dystrophin in place of the adult isoform. Forced expression of embryonic dystrophin in zebrafish using an exon-skipping approach severely impairs the mobility and muscle architecture. Moreover, reproducing Dmd exon 78 missplicing switch in mice induces muscle fibre remodelling and ultrastructural abnormalities including ringed fibres, sarcoplasmic masses or Z-band disorganization, which are characteristic features of dystrophic DM1 skeletal muscles. Thus, we propose that splicing misregulation of DMD exon 78 compromises muscle fibre maintenance and contributes to the progressive dystrophic process in DM1.

Abnormal splicing switch of DMD's penultimate exon compromises muscle fibre maintenance in myotonic dystrophy

PubMed Central

Rau, Frédérique; Lainé, Jeanne; Ramanoudjame, Laetitita; Ferry, Arnaud; Arandel, Ludovic; Delalande, Olivier; Jollet, Arnaud; Dingli, Florent; Lee, Kuang-Yung; Peccate, Cécile; Lorain, Stéphanie; Kabashi, Edor; Athanasopoulos, Takis; Koo, Taeyoung; Loew, Damarys; Swanson, Maurice S.; Le Rumeur, Elisabeth; Dickson, George; Allamand, Valérie; Marie, Joëlle; Furling, Denis

2015-01-01

Myotonic Dystrophy type 1 (DM1) is a dominant neuromuscular disease caused by nuclear-retained RNAs containing expanded CUG repeats. These toxic RNAs alter the activities of RNA splicing factors resulting in alternative splicing misregulation and muscular dysfunction. Here we show that the abnormal splicing of DMD exon 78 found in dystrophic muscles of DM1 patients is due to the functional loss of MBNL1 and leads to the re-expression of an embryonic dystrophin in place of the adult isoform. Forced expression of embryonic dystrophin in zebrafish using an exon-skipping approach severely impairs the mobility and muscle architecture. Moreover, reproducing Dmd exon 78 missplicing switch in mice induces muscle fibre remodelling and ultrastructural abnormalities including ringed fibres, sarcoplasmic masses or Z-band disorganization, which are characteristic features of dystrophic DM1 skeletal muscles. Thus, we propose that splicing misregulation of DMD exon 78 compromises muscle fibre maintenance and contributes to the progressive dystrophic process in DM1. PMID:26018658

Is adult ADHD a childhood-onset neurodevelopmental disorder? Evidence from a 4-decade longitudinal cohort study

PubMed Central

Moffitt, Terrie E.; Houts, Renate; Asherson, Philip; Belsky, Daniel W; Corcoran, David L; Hammerle, Maggie; Harrington, Honalee; Hogan, Sean; Meier, Madeline; Polanczyk, Guilherme V.; Poulton, Richie; Ramrakha, Sandhya; Sugden, Karen; Williams, Benjamin; Rohde, Luis Augusto; Caspi, Avshalom

2015-01-01

Objective Despite a prevailing assumption that adult ADHD is a childhood-onset neurodevelopmental disorder, no prospective-longitudinal study has described the childhoods of the adult-ADHD population. We report follow-back analyses of ADHD cases diagnosed in adulthood, alongside follow-forward analyses of ADHD cases diagnosed in childhood, in one cohort. Method Participants belonged to a representative birth cohort of 1,037 individuals born in Dunedin, New Zealand in 1972-73 and followed to age 38, with 95% retention. Symptoms of ADHD, associated clinical features, comorbid disorders, neuropsychological deficits, GWAS-derived polygenic risk, and life impairment indicators were assessed. Data sources were participants, parents, teachers, informants, neuropsychological testing, and administrative records. Adult ADHD diagnoses used DSM5 criteria, apart from onset-age and cross-setting corroboration, which were study outcomes. Results As expected, the childhood-ADHD group showed 6% prevalence, male excess, childhood comorbid disorders, neurocognitive deficits, polygenic risk, and, despite having outgrown their ADHD diagnosis, residual adult life impairment. As expected, the adult-ADHD group showed 3% prevalence, gender balance, adult substance dependence, adult life impairment, and treatment contact. Unexpectedly, the childhood-ADHD and adult-ADHD groups comprised virtually non-overlapping sets; 90% of adult-ADHD cases lacked a history of childhood ADHD. Also unexpectedly, the adult-ADHD group did not show tested neuropsychological deficits in childhood or adulthood, nor did they show polygenic risk for childhood ADHD. Conclusion Findings raise the possibility that adults presenting with the ADHD symptom picture may not have a childhood-onset neurodevelopmental disorder. If this finding is replicated, then the disorder's place in the classification system must be reconsidered, and research must investigate the etiology of adult ADHD. PMID:25998281

Management of adults with paediatric-onset chronic liver disease: strategic issues for transition care.

PubMed

Vajro, Pietro; Ferrante, Lorenza; Lenta, Selvaggia; Mandato, Claudia; Persico, Marcello

2014-04-01

Advances in the management of children with chronic liver disease have enabled many to survive into adulthood with or without their native livers, so that the most common of these conditions are becoming increasingly common in adult hepatology practice. Because the aetiologies of chronic liver disease in children may vary significantly from those in adulthood, adults with paediatric-onset chronic liver disease may often present with clinical manifestations unfamiliar to their adulthood physician. Transition of medical care to adult practice requires that the adulthood medical staff (primary physicians and subspecialists) have a comprehensive knowledge of childhood liver disease and their implications, and of the differences in caring for these patients. Pending still unavailable Scientific Society guidelines, this article examines causes, presentation modes, evaluation, management, and complications of the main paediatric-onset chronic liver diseases, and discusses key issues to aid in planning a program of transition from paediatric to adult patients. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Lack of Association of Mutations in Optineurin With Disease in Patients With Adult-onset Primary Open-angle Glaucoma

PubMed Central

Wiggs, Janey L.; Auguste, Josette; Allingham, R. Rand; Flor, Jason D.; Pericak-Vance, Margaret A.; Rogers, Kathryn; LaRocque, Karen R.; Graham, Felicia L.; Broomer, Bob; Del Bono, Elizabeth; Haines, Jonathan L.; Hauser, Michael

2005-01-01

Objective: To determine whether mutations in the optineurin gene contribute to susceptibility to adult-onset primary open-angle glaucoma. Methods: The optineurin gene was screened in 86 probands with adult-onset primary open-angle glaucoma and in 80 age-matched control subjects. Exons 4 and 5, containing the recurrent mutations identified in patients with normal-tension glaucoma, were sequenced in all individuals studied, while the remaining exons were screened for DNA sequence variants with denaturing high-performance liquid chromatography. Results: The recurrent mutation, Met98Lys, previously found to be associated with an increased risk of disease was found in 8 (9%) of 86 probands. We also found the Met98Lys mutation in 10% of individuals from a control population of similar age, sex, and ethnicity. Consistent segregation of the mutation with the disease was not demonstrated in any of the 8 families. No other DNA changes altering the amino acid structure of the protein were found. Conclusion: The mutations in the optineurin gene associated with normal-tension glaucoma are not associated with adult-onset primary open-angle glaucoma in this patient population. Clinical Relevance: Genetic abnormalities that render the optic nerve susceptible to degeneration are excellent candidates for genetic factors that could contribute to adult-onset primary open-angle glaucoma. Mutations in optineurin have been associated with normal-tension glaucoma, but are not associated with disease in patients with adult-onset primary open-angle glaucoma. This result may indicate that normal-tension glaucoma is not necessarily part of the phenotypic spectrum of adult open-angle glaucoma. PMID:12912697

Effects of Age, Gender, Bolus Volume, Bolus Viscosity, and Gustation on Swallowing Apnea Onset Relative to Lingual Bolus Propulsion Onset in Normal Adults

ERIC Educational Resources Information Center

Hiss, Susan G.; Strauss, Monica; Treole, Kathleen; Stuart, Andrew; Boutilier, Susan

2004-01-01

The purpose of this study was to ascertain the normal relation of swallowing apnea (SA) onset relative to lingual bolus propulsion along with factors that may alter this relation. Forty adults, composed of 10 men and 10 women in each of 2 age groups (i.e., 20-30 and 63-79 years) participated. SA onset was assessed during 5- and 20-ml bolus volumes…

No Association Between Time of Onset of Hearing Loss (Childhood Versus Adulthood) and Self-Reported Hearing Handicap in Adults.

PubMed

Aarhus, Lisa; Tambs, Kristian; Engdahl, Bo

2015-12-01

This study examined the association between time of onset of hearing loss (childhood vs. adulthood) and self-reported hearing handicap in adults. This is a population-based cohort study of 2,024 adults (mean = 48 years) with hearing loss (binaural pure-tone average 0.5-4 kHz ≥ 20 dB HL) who completed a hearing handicap questionnaire. In childhood, the same persons (N = 2,024) underwent audiometry in a school investigation (at ages 7, 10, and 13 years), in which 129 were diagnosed with sensorineural hearing loss (binaural pure-tone average 0.5-4 kHz ≥ 20 dB HL), whereas 1,895 had normal hearing thresholds. Hearing handicap was measured in adulthood as the sum-score of various speech perception and social impairment items (15 items). The sum-score increased with adult hearing threshold level (p < .001). After adjustment for adult hearing threshold level, hearing aid use, adult age, sex, and socioeconomic status, there was no significant difference in hearing handicap sum-score between the group with childhood-onset hearing loss (n = 129) and the group with adult-onset hearing loss (n = 1,895; p = .882). Self-reported hearing handicap in adults increased with hearing threshold level. After adjustment for adult hearing threshold level, this cohort study revealed no significant association between time of onset of hearing loss (childhood vs. adulthood) and self-reported hearing handicap.

Cognitive behavioural therapy with optional graded exercise therapy in patients with severe fatigue with myotonic dystrophy type 1: a multicentre, single-blind, randomised trial.

PubMed

Okkersen, Kees; Jimenez-Moreno, Cecilia; Wenninger, Stephan; Daidj, Ferroudja; Glennon, Jeffrey; Cumming, Sarah; Littleford, Roberta; Monckton, Darren G; Lochmüller, Hanns; Catt, Michael; Faber, Catharina G; Hapca, Adrian; Donnan, Peter T; Gorman, Gráinne; Bassez, Guillaume; Schoser, Benedikt; Knoop, Hans; Treweek, Shaun; van Engelen, Baziel G M

2018-06-18

Myotonic dystrophy type 1 is the most common form of muscular dystrophy in adults and leads to severe fatigue, substantial physical functional impairment, and restricted social participation. In this study, we aimed to determine whether cognitive behavioural therapy optionally combined with graded exercise compared with standard care alone improved the health status of patients with myotonic dystrophy type 1. We did a multicentre, single-blind, randomised trial, at four neuromuscular referral centres with experience in treating patients with myotonic dystrophy type 1 located in Paris (France), Munich (Germany), Nijmegen (Netherlands), and Newcastle (UK). Eligible participants were patients aged 18 years and older with a confirmed genetic diagnosis of myotonic dystrophy type 1, who were severely fatigued (ie, a score of ≥35 on the checklist-individual strength, subscale fatigue). We randomly assigned participants (1:1) to either cognitive behavioural therapy plus standard care and optional graded exercise or standard care alone. Randomisation was done via a central web-based system, stratified by study site. Cognitive behavioural therapy focused on addressing reduced patient initiative, increasing physical activity, optimising social interaction, regulating sleep-wake patterns, coping with pain, and addressing beliefs about fatigue and myotonic dystrophy type 1. Cognitive behavioural therapy was delivered over a 10-month period in 10-14 sessions. A graded exercise module could be added to cognitive behavioural therapy in Nijmegen and Newcastle. The primary outcome was the 10-month change from baseline in scores on the DM1-Activ-c scale, a measure of capacity for activity and social participation (score range 0-100). Statistical analysis of the primary outcome included all participants for whom data were available, using mixed-effects linear regression models with baseline scores as a covariate. Safety data were presented as descriptives. This trial is registered

Effects of hand-training in persons with myotonic dystrophy type 1--a randomised controlled cross-over pilot study.

PubMed

Aldehag, Anna; Jonsson, Hans; Lindblad, Jan; Kottorp, Anders; Ansved, Tor; Kierkegaard, Marie

2013-10-01

To investigate the effects of a hand-training programme on grip, pinch and wrist force, manual dexterity and activities of daily living, in adults with myotonic dystrophy type 1 (DM1). In this randomised controlled trial with a crossover design, 35 adults with DM1 were, after stratification for grip force, assigned by lot to two groups. Group A started with 12 weeks of hand training, while group B had no intervention. After a wash-out period of 12 weeks, where none received training, the order was reversed. The Grippit® was used as primary outcome measure and the hand-held Microfet2™ myometer, the Purdue Pegboard, the Canadian Occupational Performance Measure (COPM) and the Assessment of Motor and Process Skills (AMPS) were secondary outcome measures. Assessments were performed before and after training and control periods, i.e. four times altogether. Ten persons dropped out and 13 had acceptable adherence. Intention-to-treat analyses revealed significant intervention effects for isometric wrist flexor force (p = 0.048), and for COPM performance (p = 0.047) and satisfaction (p = 0.027). On an individual level, improvements were in general showed after a training period. The hand-training programme had positive effects on wrist flexor force and self-perception of occupational performance, and of satisfaction with performance. No evident detrimental effects were shown. Myotonic dystrophy type 1 (DM1) is a slowly progressive neuromuscular disease characterised by myotonia and muscle weakness and wasting. People with DM1 are often concerned about their ability to carry out ADL and to participate in, e.g. work, sports and hobbies when they gradually become weaker. This pilot study showed that a hand-training programme improved wrist flexor force and self-perception and satisfaction of occupational performance. Resistance training of hand muscles with a silicon-based putty can be a therapy option for people with DM1 in clinical practise.

The History and Timing of Depression Onset as Predictors of Young-Adult Self-Esteem

PubMed Central

Lloyd, Donald A.; Ueno, Koji

2010-01-01

Depression often emerges early in the lifecourse and is consistently shown to be associated with poor self-esteem. The three main objectives of the current study are to (1) evaluate the association between a history major depression and self-esteem in young adulthood; (2) assess the relationship between timing of depression onset and young adult self-esteem; and (3) help rule out the alternative interpretation that the relationship between major depression and self-esteem is due to state dependence bias stemming from recent depressive symptoms and stressful life events. To address these objectives we use data from a two-wave panel study based on a community sample of young adults in Miami-Dade County, Florida (n = 1,197). Results indicated a history of major depression during sensitive periods of social development is associated with negative changes in self-esteem over a two-year period during the transition to young adulthood. Among those with a history of depression, earlier onset was more problematic than later onset for young adult self-esteem, although the difference disappeared once the level of self-esteem two years prior was controlled. The linkages between the history and timing of depression onset with self-esteem were observed net of recent depressive symptoms and stressful life events, and thus robust to an alternative interpretation of state dependence. The findings support the argument that major depression, especially if it develops earlier during child-adolescent development, has negative consequences for one’s self-esteem. PMID:21860585

Anterior capsule phimosis and capsular block syndrome in a patient with Steinert myotonic dystrophy: a case report

PubMed Central

2009-01-01

A 55-year-old man with myotonic dystrophy underwent phacoemulsification with IOL implantation in the right eye. 3 months after surgery, the patient showed a decreased visual acuity and an intraocular pressure (IOP) of 30 mmHg. Slit lamp examination showed a dense fibrosis of the anterior capsule with capsulorexis' shrinkage. Gonioscopy showed a closed angle. After a YAG laser iridotomy no decrease in the IOP was detected; following surgical peeling of the anterior capsule, the slit lamp showed a distended capsular bag. A YAG laser posterior capsulotomy was performed, without decrease in the IOP. Myotonic patients need to be closely followed up after cataract surgery, because in case of CBS development a prompt posterior capsulotomy could avoid more severe complications. PMID:20062622

New onset of idiopathic bilateral ear tics in an adult.

PubMed

Agrawal, Amit; Shrestha, Rabin

2009-04-01

Tic disorders are commonly considered to be childhood syndromes. Newly presenting tic disorders during adulthood are uncommon and mostly described in relation to an acquired brain lesion or as incidental tics, particularly in context with other neurological or psychiatric diseases. Tic disorder involving the ears is extremely uncommon with only few studies in English literature. In the present case, we describe an adult patient with new-onset idiopathic tics disorder involving both ears, causing social embarrassment. In addition, our patient had recent onset of the tics without any childhood or family history of tic disorders. The single most important component of management is an accurate diagnosis. At the same time, tics should be differentiated from other movement disorders such as chorea, stereotypy, and dystonias.

Adult-onset intradural spinal teratoma: report of 18 consecutive cases and outcomes in a single center.

PubMed

Wan, Wei; Yang, Cheng; Yan, Wangjun; Liu, Tielong; Yang, Xinghai; Song, Dianwen; Xiao, Jianru

2017-07-01

Eighteen consecutive patients with adult-onset intradural spinal teratoma underwent surgical treatment in our center from 1998 to 2013. Teratoma is defined as a neoplasm composed of elements derived from three germ cell layers (ectoderm, endoderm and mesoderm). Intraspinal teratoma is extremely rare and accounts for 0.2-0.5% of all spinal cord tumors. Moreover, teratoma occurs primarily in neonates and young children. Adult-onset intradural spinal teratoma is even rare. The aim of this study was to discuss the clinical characteristics, diagnosis and therapeutic strategies of adult-onset intradural spinal teratoma. This retrospective study included 18 consecutive adult patients with intradural teratoma who were surgically treated in our center between 1998 and 2013. The clinical features, pathogenesis, diagnostic strategies and surgical outcomes were discussed. Neurological function outcomes were evaluated by the JOA scoring system. Of the 18 included patients, 4 patients received subtotal resection and the other 14 patients received total resection. All the 18 cases were diagnosed with mature teratoma. The mean follow-up period was 79.7 (median 60.5; range 27-208) months. Local recurrence occurred in two of the four patients who underwent subtotal resection and in no patient who underwent total resection. The neurologic status improved in 16 cases and remained unchanged in the other two patients. Adult-onset intradural spinal teratoma is extremely rare. To the best of our knowledge, this is the largest series of patients with this disease. Despite the slow-growth and indolent nature, radical resection remains the recommended treatment to reduce tumor recurrence.

Can long-term thiamine treatment improve the clinical outcomes of myotonic dystrophy type 1?

PubMed

Costantini, Antonio; Trevi, Erika; Pala, Maria Immacolata; Fancellu, Roberto

2016-09-01

Myotonic dystrophy type 1, also known as Steinert's disease, is an autosomal dominant disorder with multisystemic clinical features affecting the skeletal and cardiac muscles, the eyes, and the endocrine system. Thiamine (vitamin B1) is a cofactor of fundamental enzymes involved in the energetic cell metabolism; recent studies described its role in oxidative stress, protein processing, peroxisomal function, and gene expression. Thiamine deficiency is critical mainly in the central and peripheral nervous system, as well as in the muscular cells. Our aim was to investigate the potential therapeutical effects of long-term treatment with thiamine in myotonic dystrophy type 1 in an observational open-label pilot study. We described two patients with myotonic dystrophy type 1 treated with intramuscular thiamine 100 mg twice a week for 12 or 11 months. We evaluated the patients using the grading of muscle strength according to Medical Research Council (MRC), the Muscular Impairment Rating Scale (MIRS), and the Modified Barthel index. High-dose thiamine treatment was well tolerated and effective in improving the motor symptomatology, particularly the muscle strength evaluated with the MRC scale, and the patients' activities of daily living using the Modified Barthel Index. At the end of treatment, the MRC score was 5 in the proximal muscles and 2-4 in the distal muscles (the MRC score before the treatment was 3-4 and 1-3, respectively). The MIRS grade improved by 25% compared to baseline for both patients. In patient #1, the Modified Barthel Index improved by 44%, and in patient #2 by 29%. These findings suggest that clinical outcomes are improved by long-term thiamine treatment.

Management of cardiac involvement in muscular dystrophies: paediatric versus adult forms.

PubMed

Palladino, Alberto; D'Ambrosio, Paola; Papa, Andrea Antonio; Petillo, Roberta; Orsini, Chiara; Scutifero, Marianna; Nigro, Gerardo; Politano, Luisa

2016-12-01

Muscular dystrophies are a group of genetic disorders characterized by muscle degeneration and consequent substitution by fat and fibrous tissue. Cardiac involvement is an almost constant feature in a great part of these diseases, as both primary myocardial involvement and secondary involvement due to respiratory insufficiency, pulmonary hypertension or reduced mobility. Primary myocardial involvement usually begins more precociously compared to the secondary involvement. In fact the first signs of cardiomyopathy can be observed in the first decade of life in muscular dystrophies with childhood onset and later in adult form of muscular dystrophies as myotonic dystrophy type 1. At least an annual cardiac follow-up is recommended in these patients including clinical and instrumental examination (ECG, 24h Holter monitoring, ECHO), to detect cardiac involvement. A more frequent monitoring may be required according to the type of cardiomyopathy and the patient's needs. In this short review practical guide-lines are shown for physicians routinely involved in the management of these patients.

Audiovisual Integration Delayed by Stimulus Onset Asynchrony Between Auditory and Visual Stimuli in Older Adults.

PubMed

Ren, Yanna; Yang, Weiping; Nakahashi, Kohei; Takahashi, Satoshi; Wu, Jinglong

2017-02-01

Although neuronal studies have shown that audiovisual integration is regulated by temporal factors, there is still little knowledge about the impact of temporal factors on audiovisual integration in older adults. To clarify how stimulus onset asynchrony (SOA) between auditory and visual stimuli modulates age-related audiovisual integration, 20 younger adults (21-24 years) and 20 older adults (61-80 years) were instructed to perform an auditory or visual stimuli discrimination experiment. The results showed that in younger adults, audiovisual integration was altered from an enhancement (AV, A ± 50 V) to a depression (A ± 150 V). In older adults, the alterative pattern was similar to that for younger adults with the expansion of SOA; however, older adults showed significantly delayed onset for the time-window-of-integration and peak latency in all conditions, which further demonstrated that audiovisual integration was delayed more severely with the expansion of SOA, especially in the peak latency for V-preceded-A conditions in older adults. Our study suggested that audiovisual facilitative integration occurs only within a certain SOA range (e.g., -50 to 50 ms) in both younger and older adults. Moreover, our results confirm that the response for older adults was slowed and provided empirical evidence that integration ability is much more sensitive to the temporal alignment of audiovisual stimuli in older adults.

Ventricular fibrillation induced by coagulating mode bipolar electrocautery during pacemaker implantation in Myotonic Dystrophy type 1 patient.

PubMed

Russo, Vincenzo; Rago, Anna; DI Meo, Federica; Cioppa, Nadia Della; Papa, Andrea Antonio; Russo, Maria Giovanna; Nigro, Gerardo

2014-12-01

The occurrence of ventricular fibrillation, induced by bipolar electrocautery during elective dual chamber pacemaker implantation, is reported in a patient affected by Myotonic Distrophy type 1 with normal left ventricular ejection fraction.

Influences of adult-onset diabetes on orofacial pain and related health behaviors.

PubMed

Rahim-Williams, Bridgett; Tomar, Scott; Blanchard, Shirley; Riley, Joseph L

2010-01-01

This study tested the hypothesis that persons with orofacial pain and comorbid adult-onset diabetes will experience greater functional and emotional impact than persons experiencing orofacial pain without diabetes. A random-digit dialing sampling procedure was used for a disproportionate probability sample of 10,341 persons who were screened for orofacial pain in the past 6 months and diabetes. This paper reports on 1,767 individuals reporting toothache pain and 877 reporting painful oral sores. A structured telephone interview assessed diabetes history, orofacial pain characteristics, oral health-care behaviors, and emotional and functional impacts of orofacial pain. The 6-month point prevalence was 16.8 percent for toothache pain, 8.9 percent for painful oral sores, and 9.6 percent for adult-onset diabetes. Individuals with comorbid orofacial pain and adult-onset diabetes differed significantly on many of the pain characteristics and health behaviors compared with nondiabetic sufferers of orofacial pain. Diabetics were more likely than nondiabetics to have pain every day, to suffer negative emotions associated with pain, to experience disruption of daily activities and sleep, to make an emergency room visit for orofacial pain, and to report the current need for a pain-related health-care visit. Although diabetes is well known to be associated with neuropathic pain, these results indicate that the experience of nociceptive pain is exacerbated by diabetes. Findings have significance for the subjective experience of oral pain, dental-care outcomes, and health-related quality of life associated with oral-health outcomes among individuals with diabetes.

No Association Between Time of Onset of Hearing Loss (Childhood Versus Adulthood) and Self-Reported Hearing Handicap in Adults

PubMed Central

Tambs, Kristian; Engdahl, Bo

2015-01-01

Purpose This study examined the association between time of onset of hearing loss (childhood vs. adulthood) and self-reported hearing handicap in adults. Methods This is a population-based cohort study of 2,024 adults (mean = 48 years) with hearing loss (binaural pure-tone average 0.5–4 kHz ≥ 20 dB HL) who completed a hearing handicap questionnaire. In childhood, the same persons (N = 2,024) underwent audiometry in a school investigation (at ages 7, 10, and 13 years), in which 129 were diagnosed with sensorineural hearing loss (binaural pure-tone average 0.5–4 kHz ≥ 20 dB HL), whereas 1,895 had normal hearing thresholds. Results Hearing handicap was measured in adulthood as the sum-score of various speech perception and social impairment items (15 items). The sum-score increased with adult hearing threshold level (p < .001). After adjustment for adult hearing threshold level, hearing aid use, adult age, sex, and socioeconomic status, there was no significant difference in hearing handicap sum-score between the group with childhood-onset hearing loss (n = 129) and the group with adult-onset hearing loss (n = 1,895; p = .882). Conclusion Self-reported hearing handicap in adults increased with hearing threshold level. After adjustment for adult hearing threshold level, this cohort study revealed no significant association between time of onset of hearing loss (childhood vs. adulthood) and self-reported hearing handicap. PMID:26649831

Adult-Onset NREM Parasomnia with Hypnopompic Hallucinatory Pain: A Case Report

PubMed Central

Mantoan, Laura; Eriksson, Sofia H.; Nisbet, Angus P.; Walker, Matthew C.

2013-01-01

We report the case of a 43-year-old woman presenting with nocturnal episodes of pain and screaming during sleep starting at age 30. There was no childhood or family history of parasomnia. The events had gradually become more frequent over the years, occurring in the first half of the night within 2 h of sleep onset. There were no triggers, and she had partial amnesia for the events. A diagnosis of adult-onset sleep terrors was made on clinical grounds and supported polysomnographically. Seizures and periodic limb movements were excluded as triggering factors. There was some mild sleep disordered breathing (predominantly non-desaturating hypopnea with a propensity for REM sleep of debatable significance). Imaging of the brain and spine and neurophysiological investigations ruled out lesions, entrapments, or neuropathies as possible causes of pain. Treatment (clonazepam, paroxetine, or gabapentin) was poorly tolerated and made no difference to the nocturnal episodes, while trazodone worsened them. This is the first report of hypnopompic psychic pain in association with a NREM parasomnia. We hypothesize that the pain may represent a sensory hallucination analogous to the more commonly recognized visual NREM parasomnia-associated hypnopompic visual hallucinations and that, as such, it may arise during arousal of the sensory neocortex as confabulatory response. Citation: Mantoan L; Eriksson SH; Nisbet AP; Walker MC. Adult-onset nrem parasomnia with hypnopompic hallucinatory pain: a case report. SLEEP 2013;36(2):287–290. PMID:23372277

Knowledge, views, and experience of 25 women with myotonic dystrophy.

PubMed

Faulkner, C L; Kingston, H M

1998-12-01

Twenty-five affected women of reproductive age known to the North West Regional Genetics Family Register (NWRGFR) were interviewed. A semistructured questionnaire, completed by the interviewer, was used to assess understanding and experience of the clinical and genetic aspects of myotonic dystrophy (MD) and attitudes to prenatal diagnosis (PND). Characteristic features of MD (muscle weakness and wasting and myotonia) were well known. Knowledge of other features and complications reflected experience. All subjects were aware that MD is inherited, but only 56% (14/25) knew the risk to their own children and subjects tended to overestimate this risk. Anticipation and maternal transmission of congenital myotonic dystrophy (CMD) were often misunderstood. Almost half of the subjects (12/25) perceived themselves to be moderately or severely affected and 40% (10/25) felt that their symptoms restricted daily life. Feelings of devastation, depression, worry about the future, and guilt at the risk of transmission to their children were described. Many subjects (10/25) said that the worst aspect of MD is the risk of transmission to their children. Over half (14/25) said that the risk of transmitting MD had influenced or would influence their own reproduction. Three-quarters of subjects who felt that MD had influenced their reproductive decisions (9/12) chose to limit their family or have no children; only 25% (3/12) requested PND. Subjects felt that the lack of information concerning clinical severity made PND for MD difficult to consider.

Prevalence and correlates of bipolar I disorder among adults with primary youth-onset anxiety disorders.

PubMed

Goldstein, Benjamin I; Levitt, Anthony J

2007-11-01

It is of potentially great public health importance to determine whether youth-onset anxiety disorders are associated with the increased prevalence of subsequent bipolar I disorder (BD) among adults, and to identify risk factors for BD in this population. The 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions was used to identify respondents with social phobia, panic disorder, or generalized anxiety disorder that onset in youth (<19 years) and was not preceded by a major depressive, manic, or mixed episode (N=1571; 572 males, 999 females). The prevalence of BD among subjects with, versus without, these youth-onset anxiety disorders was examined. Variables that could be associated with the increased risk of BD among subjects with youth-onset anxiety disorders were examined, including conduct disorder, youth-onset substance use disorders (SUD), and family history of depression and/or alcoholism. Analyses were computed separately for males and females. The prevalence of BD was significantly greater among adults with, versus without, primary youth-onset anxiety disorders for both males (15.9% vs 2.7%; chi2=318.4, df=1, p<0.001) and females (13.8% vs 2.9%; chi2=346.2, df=1, p<0.001). Youth-onset anxiety disorders remained significantly associated with BD after controlling for interceding major depression, and this was true for each of the specific anxiety disorders examined. Among males with youth-onset primary anxiety disorders, conduct disorder and loaded family history of depression were associated with significantly increased risk of BD. Among females, conduct disorder and loaded family history of alcoholism were associated with significantly increased risk of BD. The prevalence of BD was elevated among subjects with youth-onset primary anxiety disorders, particularly if comorbid conduct disorder was present. Future studies are needed to confirm these findings prospectively, and to develop preventive strategies for populations at risk.

Myotonic dystrophytype 1 - report of non-24-h sleep-wake disorder with excessive daytime sleepiness.

PubMed

Filho, Lucio Huebra Pimentel; Gomes, Ana Carolina Dias; Gonçalves, Bruno; Tufik, Sergio; Coelho, Fernando Morgadinho

2018-05-15

Myotonic dystrophy (MD) is a neuromuscular disease with myotonia, progressive weakness, and involvement of CNS, heart, and gastrointestinal system. Excessive daytime sleepiness (EDS) in myotonic dystrophy type 1 (MD1) is related to sleep breathing diseases, restless leg syndrome, periodic limb movements during sleep and narcoleptic-like phenotype. However, authors highlight a central dysfunction of sleep regulation. We describe a 26-year-old, female, MD1 patient with EDS. Sleep diary/actigraphy evidenced two different circadian periods with values of 1442 and 1522 min. Agomelatine, 50 mg at night, was prescribed with improvement of the circadian rhythm and complaints of sleepiness. The identification of unanticipated causes of EDS, such as circadian rhythm disorders permits an appropriated treatment. As we know, it is the first relate of non-24-h sleep-wake disorder in patient with MD1. Sleep diary and actigraphy could be good options to investigate sleep-wake cycle disorder in patients with MD and EDS.

Occupational characteristics of adults with pediatric-onset spinal cord injury.

PubMed

Hwang, Miriam; Zebracki, Kathy; Vogel, Lawrence C

2015-01-01

Employment rates among individuals with spinal cord injury (SCI) are lower than in the general population and little is known about the specific occupations in which they are employed. To describe specific occupations of adults with pediatric-onset SCI using the 2010 Standard Occupational Classification (SOC) system and to determine associations between SOC occupations and demographic factors. Cross-sectional data specific to education and employment were collected from the last interviews of a larger longitudinal study. Occupations were categorized according to the 2010 SOC system. SOC groups were compared within gender level of injury and final education. Of the 461 total participants 219 (47.5%) were employed and specific occupations were available for 179. Among the SOC groups Education Law Community Service Arts and Media Occupations were most prevalent (30.2%) followed by Management Business and Finance Occupations (21.1%) Computer Engineering and Science Occupations (10.6%) Administrative and Office Support Occupations (10.0%) Service Occupations (7.3%) Healthcare Practitioners and Technical Occupations (3.9%) and Production Occupations (3.4%). Differences were found in the distribution of SOC groups between gender levels of injury and final education groups. A wide variety of occupations were reported in adults with pediatric-onset SCI generally in concordance with final education and functional ability levels.

Hormonal therapy (hCG and rhFSH) for infertile men with adult-onset idiopathic hypogonadotropic hypogonadism.

PubMed

Kobori, Yoshitomo; Suzuki, Keisuke; Iwahata, Toshiyuki; Shin, Takeshi; Sato, Ryo; Nishio, Kojiro; Yagi, Hiroshi; Arai, Gaku; Soh, Shigehiro; Okada, Hiroshi

2015-04-01

Adult-onset idiopathic male hypogonadotropic hypogonadism (IMHH) is a very rare but treatable disease. This study was conducted to examine the efficacy and safety of a combination of human chorionic gonadotropin (hCG) and recombinant human follicle-stimulating hormone (rhFSH) for inducing spermatogenesis in men with adult-onset IMHH. Seven men (34-45 years of age) with azoospermia and/or sexual dysfunction, with a low serum testosterone concentration, and apulsatile secretion of luteinizing hormone, were referred to our hospital for infertility. All had normal secondary sexual characteristics. Thorough endocrinologic examination and magnetic resonance imaging revealed no identifiable cause of hypogonadotropic hypogonadism. Adult-onset IMHH was diagnosed in all cases and treatment was started with 150 IU rhFSH and 5,000 IU hCG, both administered two times per week. Spermatogenesis was restored in five of the seven patients. During treatment one patient achieved spontaneous pregnancy with his wife, and spermatozoa recovered from the other four patients were frozen for future use in intracytoplasmic sperm injection.

Myocarditis in adult-onset still disease.

PubMed

Gerfaud-Valentin, Mathieu; Sève, Pascal; Iwaz, Jean; Gagnard, Anne; Broussolle, Christiane; Durieu, Isabelle; Ninet, Jacques; Hot, Arnaud

2014-10-01

This study highlights the clinical features, treatments, and outcomes of the rare myocarditis in adult-onset Still disease (AOSD). Among a case series of 57 patients fulfilling either Yamaguchi or Fautrel AOSD criteria and seen between 1998 and 2010, we identified 4 cases of myocarditis. From a comprehensive literature review, we collected 20 additional cases of myocarditis-complicated AOSD. The characteristics of patients with myocarditis were compared with those of AOSD patients without myocarditis.In these 24 myocarditis-complicated AOSD cases, myocarditis occurred early and was present at AOSD onset in 54% of the cases. Myocarditis was often symptomatic (96% of patients) with nonspecific electrocardiographic abnormalities (79% of patients) and a left ventricle ejection fraction ≤50% (67% of patients). Cardiac magnetic resonance imaging and endomyocardial biopsies showed features consistent with myocarditis in 4 patients and a mononuclear interstitial inflammatory infiltrate in 4 others. Steroids alone were effective in 50% of patients with myocarditis. Intravenous immunoglobulins, methotrexate, and tumor necrosis factor-α-blockers were also prescribed and often found effective. Only 1 patient died from cardiogenic shock. Patients with myocarditis-complicated AOSD were younger and more frequently male than patients with AOSD alone. Pericarditis was more frequent in the myocarditis group; white blood cell count, polymorphonuclear cell count, and serum ferritin levels were also higher.Myocarditis is a potentially life-threatening complication of AOSD but responds positively to steroids and other immunomodulatory drugs. Its prognosis remains good (only 1 death occurred), but the condition requires close monitoring of heart function.

Myocarditis in Adult-Onset Still Disease

PubMed Central

Gerfaud-Valentin, Mathieu; Sève, Pascal; Iwaz, Jean; Gagnard, Anne; Broussolle, Christiane; Durieu, Isabelle; Ninet, Jacques; Hot, Arnaud

2014-01-01

Abstract This study highlights the clinical features, treatments, and outcomes of the rare myocarditis in adult-onset Still disease (AOSD). Among a case series of 57 patients fulfilling either Yamaguchi or Fautrel AOSD criteria and seen between 1998 and 2010, we identified 4 cases of myocarditis. From a comprehensive literature review, we collected 20 additional cases of myocarditis-complicated AOSD. The characteristics of patients with myocarditis were compared with those of AOSD patients without myocarditis. In these 24 myocarditis-complicated AOSD cases, myocarditis occurred early and was present at AOSD onset in 54% of the cases. Myocarditis was often symptomatic (96% of patients) with nonspecific electrocardiographic abnormalities (79% of patients) and a left ventricle ejection fraction ≤50% (67% of patients). Cardiac magnetic resonance imaging and endomyocardial biopsies showed features consistent with myocarditis in 4 patients and a mononuclear interstitial inflammatory infiltrate in 4 others. Steroids alone were effective in 50% of patients with myocarditis. Intravenous immunoglobulins, methotrexate, and tumor necrosis factor-α-blockers were also prescribed and often found effective. Only 1 patient died from cardiogenic shock. Patients with myocarditis-complicated AOSD were younger and more frequently male than patients with AOSD alone. Pericarditis was more frequent in the myocarditis group; white blood cell count, polymorphonuclear cell count, and serum ferritin levels were also higher. Myocarditis is a potentially life-threatening complication of AOSD but responds positively to steroids and other immunomodulatory drugs. Its prognosis remains good (only 1 death occurred), but the condition requires close monitoring of heart function. PMID:25398063

How does dementia onset in parents influence unmarried adult children's wealth.

PubMed

Arora, Kanika

2016-03-01

There is a growing concern that long-term care (LTC) needs of older adults lead to negative financial consequences for their family members. This paper examines whether the onset of dementia in parents influences wealth change among unmarried adult children regardless of their status as informal caregivers. Longitudinal data from seven waves (1998-2010) of the Health and Retirement Study (1540 person-wave observations) are used to analyze this question. Unconditional quantile regressions demonstrate that as a result of parental dementia diagnosis, unmarried adult children have lower wealth accumulation above the median of the wealth change distribution. These effects are more pronounced for unmarried adult children without siblings. Further, this response is observed to persist in the subsequent period as well. Both losses in labor income and nursing home expenditures may play a role in leading to wealth declines. Copyright © 2016 Elsevier Ltd. All rights reserved.

Adult-Onset Hypogonadism.

PubMed

Khera, Mohit; Broderick, Gregory A; Carson, Culley C; Dobs, Adrian S; Faraday, Martha M; Goldstein, Irwin; Hakim, Lawrence S; Hellstrom, Wayne J G; Kacker, Ravi; Köhler, Tobias S; Mills, Jesse N; Miner, Martin; Sadeghi-Nejad, Hossein; Seftel, Allen D; Sharlip, Ira D; Winters, Stephen J; Burnett, Arthur L

2016-07-01

In August 2015, an expert colloquium commissioned by the Sexual Medicine Society of North America (SMSNA) convened in Washington, DC, to discuss the common clinical scenario of men who present with low testosterone (T) and associated signs and symptoms accompanied by low or normal gonadotropin levels. This syndrome is not classical primary (testicular failure) or secondary (pituitary or hypothalamic failure) hypogonadism because it may have elements of both presentations. The panel designated this syndrome adult-onset hypogonadism (AOH) because it occurs commonly in middle-age and older men. The SMSNA is a not-for-profit society established in 1994 to promote, encourage, and support the highest standards of practice, research, education, and ethics in the study of human sexual function and dysfunction. The panel consisted of 17 experts in men's health, sexual medicine, urology, endocrinology, and methodology. Participants declared potential conflicts of interest and were SMSNA members and nonmembers. The panel deliberated regarding a diagnostic process to document signs and symptoms of AOH, the rationale for T therapy, and a monitoring protocol for T-treated patients. The evaluation and management of hypogonadal syndromes have been addressed in recent publications (ie, the Endocrine Society, the American Urological Association, and the International Society for Sexual Medicine). The primary purpose of this document was to support health care professionals in the development of a deeper understanding of AOH, particularly in how it differs from classical primary and secondary hypogonadism, and to provide a conceptual framework to guide its diagnosis, treatment, and follow-up. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

[Steinert disease: abnormal onset or "casual" diagnosis?].

PubMed

Pempinello, R; Iannece, M D; Di Pierro, M

2001-01-01

The most frequent myopathy is "Steinert's disease" (also called myotonic dystrophy). We present a case of particular interest due to the way diagnosis was made. A 20-year-old male was transferred to our Department from another Hospital with a diagnosis of "acute liver disease". He presented with fever (39 degrees C), tetrahyposthenia, dehydration and spatial-temporal disorientation. The most apparent laboratory data was a significant increase in serum levels of creatine phosphokinase (196,260 IU/L; normal values < 50 IU/L). After therapy based on parenteral nutrition and steroids, our patient improved progressively, with normalization of laboratory values. Muscle biopsy and electromyography yielded a diagnosis of Steinert's disease, and the patient's mother was found to be the carrier of a myotonine-kinase gene mutation. In this case, the onset of what appeared to be an influenza-A virus infection (the only positive data observed in the serological analysis) permitted the diagnosis of a hereditary myopathy that had remained asymptomatic up to that time.

[Perioperative treatment of a patient with myotonic muscular dystrophy (Curschmann-Steinert disease)].

PubMed

Thölke, M H; Tolksdorf, W; Mitrenga, I

1991-04-01

The perioperative period is hazardous for patients with neuromuscular disorder. In case of dystrophia myotonica the anaesthesist must avoid all stimuli that may cause a myotonic crisis. If neuromuscular blockade is required, the moderately long-acting vecuronium bromide seems to be the drug of first choice. Blockade and recovery should be monitored. Postoperative pulmonary complications can be minimised by using regional anaesthetic techniques including epidural anaesthesia with local anaesthetics and/or opioids.

Excessive and premature new-onset cardiovascular disease among adults with bipolar disorder in the US NESARC cohort.

PubMed

Goldstein, Benjamin I; Schaffer, Ayal; Wang, Shuai; Blanco, Carlos

2015-02-01

Cross-sectional studies demonstrate increased prevalence of cardiovascular disease (CVD) among adults with bipolar disorder. However, there is a paucity of prospective data regarding new-onset CVD among adults with bipolar disorder. Analyses compared the 3-year incidence of CVD (via participant-reported physician diagnoses) among participants with DSM-IV diagnoses of bipolar I disorder (n = 1,047), bipolar II disorder (n = 392), major depressive disorder (MDD; n = 4,396), or controls (n = 26,266), who completed Wave 1 (2001-2002) and Wave 2 (2004-2005) of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Analyses also compared the age of participants with new-onset CVD across groups. Multivariable analyses controlled for age, sex, race, cigarette smoking, hypertension, obesity, and alcohol and drug use disorders. The 3-year incidence of CVD among adults with bipolar I disorder, bipolar II disorder, MDD, and among controls was 6.30%, 5.74%, 3.98%, and 3.70%, respectively. The covariate-adjusted incidence of CVD was significantly greater among participants with bipolar I and II disorders versus controls and versus participants with MDD. Adjusted odds ratios (95% CI) were 2.58 (1.84-3.61; P < .0001) for bipolar I disorder vs controls; 2.76 (1.60-4.74; P = .0004) for bipolar II disorder vs controls; 2.11 (1.46-3.04; P = .0001) for bipolar I disorder vs MDD; 2.25 (1.26-4.01; P = .007) for bipolar II disorder vs MDD; and 1.22 (0.99-1.51; P = .06) for MDD vs controls. Bipolar I disorder participants with new-onset CVD were 10.70 ± 2.77 years younger than MDD participants with new-onset CVD and 16.78 ± 2.51 years younger than controls. Bipolar II disorder participants with new-onset CVD were 7.92 ± 3.27 years younger than MDD participants with new-onset CVD and 13.99 ± 2.79 years younger than controls. Adults with bipolar disorder are at significantly and meaningfully increased risk to develop CVD over the course of 3 years, even as compared

Assessing the Dim Light Melatonin Onset in Adults with Autism Spectrum Disorder and No Comorbid Intellectual Disability

ERIC Educational Resources Information Center

Baker, Emma K.; Richdale, Amanda L.; Hazi, Agnes; Prendergast, Luke A.

2017-01-01

This study assessed melatonin levels and the dim light melatonin onset (DLMO) in adults with Autism Spectrum Disorder (ASD) and also investigated the relationships between melatonin and objectively measured sleep parameters. Sixteen adults with ASD (ASD-Only), 12 adults with ASD medicated for comorbid diagnoses of anxiety and/or depression…

Real-life 10-year retention rate of first-line anti-TNF drugs for inflammatory arthritides in adult- and juvenile-onset populations: similarities and differences.

PubMed

Favalli, Ennio Giulio; Pontikaki, Irene; Becciolini, Andrea; Biggioggero, Martina; Ughi, Nicola; Romano, Micol; Crotti, Chiara; Gattinara, Maurizio; Gerloni, Valeria; Marchesoni, Antonio; Meroni, Pier Luigi

2017-08-01

The aim of this study is to retrospectively analyze 10-year drug survival of first-line TNF inhibitor (TNFi) in rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), and juvenile idiopathic arthritis (JIA) patients, comparing withdrawal rates and discontinuation pattern between adult- and juvenile-onset populations. RA, AS, PsA, and JIA patients treated with infliximab, etanercept, or adalimumab as first TNFi between 1999 and 2015 were extracted from a local registry. Drug survival up to 10-year follow-up was evaluated by the Kaplan-Meier method and compared according to age (adult vs juvenile onset), TNFi agent, and discontinuation reason by a stratified log-rank test. Three hundred sixty JIA (205 etanercept, 66 adalimumab, and 89 infliximab) and 951 (607 RA, 188 AS, and 156 PsA) adult patients (464 infliximab, 262 adalimumab, and 225 etanercept) were included. After exclusion of systemic-onset JIA (18.5%), overall 10-year retention rate was 31.8%, with no difference between adult- and juvenile-onset patients (32.1 and 30.2%, respectively; HR 0.938 [95% CI 0.782-1.125]). Etanercept showed the highest drug survival in adult-onset population (p < 0.0001 vs both monoclonal antibodies) and infliximab the lowest in juvenile-onset population (p = 0.005 vs adalimumab and p < 0.0001 vs etanercept). Inefficacy was the most frequent reason for TNFi withdrawal in adult population (29.75%) with a significantly higher risk of discontinuation than in juvenile-onset subgroup (HR 1.390 [95% CI 1.060-1.824]). Serious infections and malignancies caused TNFi withdrawal only in adult whereas gastrointestinal, neuropsychiatric, and ocular complications quite only in juvenile patients. Despite a similar 10-year drug survival, adult- and juvenile-onset subpopulations showed a significantly different pattern of TNFi reasons for discontinuation.

Occupational Characteristics of Adults with Pediatric-Onset Spinal Cord Injury

PubMed Central

Zebracki, Kathy; Vogel, Lawrence C.

2015-01-01

Background: Employment rates among individuals with spinal cord injury (SCI) are lower than in the general population and little is known about the specific occupations in which they are employed. Objectives: To describe specific occupations of adults with pediatric-onset SCI using the 2010 Standard Occupational Classification (SOC) system and to determine associations between SOC occupations and demographic factors. Methods: Cross-sectional data specific to education and employment were collected from the last interviews of a larger longitudinal study. Occupations were categorized according to the 2010 SOC system. SOC groups were compared within gender level of injury and final education. Results: Of the 461 total participants 219 (47.5%) were employed and specific occupations were available for 179. Among the SOC groups Education Law Community Service Arts and Media Occupations were most prevalent (30.2%) followed by Management Business and Finance Occupations (21.1%) Computer Engineering and Science Occupations (10.6%) Administrative and Office Support Occupations (10.0%) Service Occupations (7.3%) Healthcare Practitioners and Technical Occupations (3.9%) and Production Occupations (3.4%). Differences were found in the distribution of SOC groups between gender levels of injury and final education groups. Conclusion: A wide variety of occupations were reported in adults with pediatric-onset SCI generally in concordance with final education and functional ability levels. PMID:25762856

Posture and gait abilities in patients with myotonic dystrophy (Steinert disease). Evaluation on the short-term of a rehabilitation program.

PubMed

Missaoui, B; Rakotovao, E; Bendaya, S; Mane, M; Pichon, B; Faucher, M; Thoumie, P

2010-01-01

To evaluate the effects of a rehabilitation program in terms of balance, gait and muscle strength in a population of patients with myotonic dystrophy. Twenty patients benefited, as outpatients in a hospital setting, from a rehabilitation program with clinical and instrumental evaluations. The evaluation focused on quantitative balance measurement by clinical and stabilometer tests, gait assessed by Locometre and extensors and flexors knee muscle strength measured in isokinetic concentric mode at 60°/s. After the rehabilitation program, we observed a significant improvement in the patients' balance capacities measured with the Berg Balance Scale (BBS), fast gait speed and muscle strength. However, the instrumental evaluation did not report any gains for static balance and spontaneous gait speed after the training program. No correlation was found between the various improvements. A rehabilitation program focused on strength, gait and balance allowed for significant improvements in some parameters of myotonic dystrophy. These results attest to the relevance of a short-term rehabilitation protocol for these patients in the framework of a multidisciplinary therapeutic care. The disparity observed in the results measured for these patients suggest the contribution of cognitive involvement in the limitations felt by patients with myotonic dystrophy in the areas of gait and balance. Copyright 2010 Elsevier Masson SAS. All rights reserved.

Developmental evaluation of family functioning deficits in youths and young adults with childhood-onset bipolar disorder.

PubMed

MacPherson, Heather A; Ruggieri, Amanda L; Christensen, Rachel E; Schettini, Elana; Kim, Kerri L; Thomas, Sarah A; Dickstein, Daniel P

2018-08-01

Childhood-onset bipolar disorder (BD) is a serious condition that affects the patient and family. While research has documented familial dysfunction in individuals with BD, no studies have compared developmental differences in family functioning in youths with BD vs. adults with prospectively verified childhood-onset BD. The Family Assessment Device (FAD) was used to examine family functioning in participants with childhood-onset BD (n = 116) vs. healthy controls (HCs) (n = 108), ages 7-30 years, using multivariate analysis of covariance and multiple linear regression. Participants with BD had significantly worse family functioning in all domains (problem solving, communication, roles, affective responsiveness, affective involvement, behavior control, general functioning) compared to HCs, regardless of age, IQ, and socioeconomic status. Post-hoc analyses suggested no influence for mood state, global functioning, comorbidity, and most medications, despite youths with BD presenting with greater severity in these areas than adults. Post-hoc tests eliminating participants taking lithium (n = 17) showed a significant diagnosis-by-age interaction: youths with BD had worse family problem solving and communication relative to HCs. Limitations include the cross-sectional design, clinical differences in youths vs. adults with BD, ambiguity in FAD instructions, participant-only report of family functioning, and lack of data on psychosocial treatments. Familial dysfunction is common in childhood-onset BD and endures into adulthood. Early identification and treatment of both individual and family impairments is crucial. Further investigation into multi-level, family-based mechanisms underlying childhood-onset BD may clarify the role family factors play in the disorder, and offer avenues for the development of novel, family-focused therapeutic strategies. Copyright © 2018 Elsevier B.V. All rights reserved.

A longitudinal study of adult-onset asthma incidence among HMO members.

PubMed

Sama, Susan R; Hunt, Phillip R; Cirillo, C I H Priscilla; Marx, Arminda; Rosiello, Richard A; Henneberger, Paul K; Milton, Donald K

2003-08-07

HMO databases offer an opportunity for community based epidemiologic studies of asthma incidence, etiology and treatment. The incidence of asthma in HMO populations and the utility of HMO data, including use of computerized algorithms and manual review of medical charts for determining etiologic factors has not been fully explored. We identified adult-onset asthma, using computerized record searches in a New England HMO. Monthly, our software applied exclusion and inclusion criteria to identify an "at-risk" population and "potential cases". Electronic and paper medical records from the past year were then reviewed for each potential case. Persons with other respiratory diseases or insignificant treatment for asthma were excluded. Confirmed adult-onset asthma (AOA) cases were defined as those potential cases with either new-onset asthma or reactivated mild intermittent asthma that had been quiescent for at least one year. We validated the methods by reviewing charts of selected subjects rejected by the algorithm. The algorithm was 93 to 99.3% sensitive and 99.6% specific. Sixty-three percent (n = 469) of potential cases were confirmed as AOA. Two thirds of confirmed cases were women with an average age of 34.8 (SD 11.8), and 45% had no evidence of previous asthma diagnosis. The annualized monthly rate of AOA ranged from 4.1 to 11.4 per 1000 at-risk members. Physicians most commonly attribute asthma to infection (59%) and allergy (14%). New-onset cases were more likely attributed to infection, while reactivated cases were more associated with allergies. Medical charts included a discussion of work exposures in relation to asthma in only 32 (7%) cases. Twenty-three of these (72%) indicated there was an association between asthma and workplace exposures for an overall rate of work-related asthma of 4.9%. Computerized HMO records can be successfully used to identify AOA. Manual review of these records is important to confirm case status and is useful in evaluation of

Endocrine Disruptor Vinclozolin Induced Epigenetic Transgenerational Adult-Onset Disease

PubMed Central

Anway, Matthew D.; Leathers, Charles; Skinner, Michael K.

2018-01-01

The fetal basis of adult disease is poorly understood on a molecular level and cannot be solely attributed to genetic mutations or a single etiology. Embryonic exposure to environmental compounds has been shown to promote various disease states or lesions in the first generation (F1). The current study used the endocrine disruptor vinclozolin (antiandrogenic compound) in a transient embryonic exposure at the time of gonadal sex determination in rats. Adult animals from the F1 generation and all subsequent generations examined (F1–F4) developed a number of disease states or tissue abnormalities including prostate disease, kidney disease, immune system abnormalities, testis abnormalities, and tumor development (e.g. breast). In addition, a number of blood abnormalities developed including hypercholesterolemia. The incidence or prevalence of these transgenerational disease states was high and consistent across all generations (F1–F4) and, based on data from a previous study, appears to be due in part to epigenetic alterations in the male germ line. The observations demonstrate that an environmental compound, endocrine disruptor, can induce transgenerational disease states or abnormalities, and this suggests a potential epigenetic etiology and molecular basis of adult onset disease. PMID:16973726

Brain pathology in myotonic dystrophy: when tauopathy meets spliceopathy and RNAopathy

PubMed Central

Caillet-Boudin, Marie-Laure; Fernandez-Gomez, Francisco-Jose; Tran, Hélène; Dhaenens, Claire-Marie; Buee, Luc; Sergeant, Nicolas

2013-01-01

Myotonic dystrophy (DM) of type 1 and 2 (DM1 and DM2) are inherited autosomal dominant diseases caused by dynamic and unstable expanded microsatellite sequences (CTG and CCTG, respectively) in the non-coding regions of the genes DMPK and ZNF9, respectively. These mutations result in the intranuclear accumulation of mutated transcripts and the mis-splicing of numerous transcripts. This so-called RNA gain of toxic function is the main feature of an emerging group of pathologies known as RNAopathies. Interestingly, in addition to these RNA inclusions, called foci, the presence of neurofibrillary tangles (NFT) in patient brains also distinguishes DM as a tauopathy. Tauopathies are a group of nearly 30 neurodegenerative diseases that are characterized by intraneuronal protein aggregates of the microtubule-associated protein Tau (MAPT) in patient brains. Furthermore, a number of neurodegenerative diseases involve the dysregulation of splicing regulating factors and have been characterized as spliceopathies. Thus, myotonic dystrophies are pathologies resulting from the interplay among RNAopathy, spliceopathy, and tauopathy. This review will describe how these processes contribute to neurodegeneration. We will first focus on the tauopathy associated with DM1, including clinical symptoms, brain histology, and molecular mechanisms. We will also discuss the features of DM1 that are shared by other tauopathies and, consequently, might participate in the development of a tauopathy. Moreover, we will discuss the determinants common to both RNAopathies and spliceopathies that could interfere with tau-related neurodegeneration. PMID:24409116

Benign and malignant tumors in the UK myotonic dystrophy patient registry.

PubMed

Alsaggaf, Rotana; Wang, Youjin; Marini-Bettolo, Chiara; Wood, Libby; Nikolenko, Nikoletta; Lochmüller, Hanns; Greene, Mark H; Gadalla, Shahinaz M

2018-02-01

In light of recent evidence indicating that cancer is part of the myotonic dystrophy (DM) phenotype, we assessed the prevalence of benign and malignant tumors among 220 patients enrolled in the UK Myotonic Dystrophy Patient Registry and evaluated factors associated with their development. A survey was distributed to collect tumor history and lifestyle information. We used multinomial logistic regression for the analysis. Thirty-nine benign (30 patients), and 16 malignant (15 patients) tumors were reported. Increasing age (odds ratio [OR] = 1.13, 95% confidence interval [CI] = 1.05-1.21, P = 0.001) and earlier age at DM diagnosis (OR = 1.06, 95% CI = 1.00-1.13, P = 0.04) were associated with benign and malignant tumors (OR = 1.20, 95% CI = 1.10-1.30, P < 0.001 and OR = 1.08, 95% CI = 1.01-1.15, P = 0.02, respectively). Female gender was associated with benign tumors only (OR = 6.43, 95% CI = 1.79-23.04, P = 0.004). No associations were observed between tumors and smoking (P = 0.24), alcohol consumption (P = 0.50), or body mass index (P = 0.21). Our results confirm previous findings suggesting a limited role for common lifestyle factors and a potential genetic contribution in DM tumor predisposition. Muscle Nerve 57: 316-320, 2018. © 2017 Wiley Periodicals, Inc.

Adult-onset diabetes among Arabs and Jews in Israel: a population-based study.

PubMed

Kalter-Leibovici, O; Chetrit, A; Lubin, F; Atamna, A; Alpert, G; Ziv, A; Abu-Saad, K; Murad, H; Eilat-Adar, S; Goldbourt, U

2012-06-01

To study the age at presentation and factors associated with adult-onset diabetes (≥ 20 years) among Arabs and Jews in Israel. Participants (n = 1100) were randomly selected from the urban population of the Hadera District in Israel. The study sample was stratified into equal groups according to sex, ethnicity (Arabs and Jews) and age. Information on age at diabetes presentation, family history of diabetes, history of gestational diabetes, socio-demographic and lifestyle characteristics was obtained through personal interviews. Self reports of diabetes were compared with medical records and were found reliable (κ = 0.87). The risk for diabetes was calculated using Kaplan-Meier survival analysis. Factors associated with diabetes in both ethnic groups were studied using Cox proportional hazard model. The prevalence of adult-onset diabetes was 21% among Arabs and 12% among Jews. Arab participants were younger than Jews at diabetes presentation. By the age of 57 years, 25% of Arabs had diagnosed diabetes; the corresponding age among Jews was 68 years, a difference of 11 years (P < 0.001). The greater risk for diabetes among Arabs was independent of lifestyle factors, family history of diabetes and, among women, history of gestational diabetes; adjusted hazard ratio 1.70; 95% confidence interval 1.19-2.43. Arabs in Israel are at greater risk for adult-onset diabetes than Jews and are younger at diabetes presentation. Culturally sensitive interventions aimed at maintaining normal body weight and active lifestyle should be targeted at this population. Possible genetic factors and gene-environmental interactions underlying the high risk for diabetes among Arabs should be investigated. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.

Delay in the Diagnosis of Adult-Onset Still’s Disease

PubMed Central

Pham, Cindy

2017-01-01

Adult-onset Still’s disease (AOSD) is a systemic autoinflammatory disease characterized by symptoms including spiking fever, arthralgia, myalgia, maculopapular rash, and pharyngitis. The lack of diagnostic biomarker, non-specific clinical presentation, and the rarity of AOSD often result in a significant delay in diagnosis and treatment. While the average time of initial presentation to diagnosis is four months, we present a case of AOSD diagnosis three years after initial onset of classical symptoms. By reporting the case of delayed diagnosis for AOSD, we hope to raise awareness in our medical community about the diagnostic difficulty in AOSD. The present case describes an otherwise healthy male who presented with typical symptoms of AOSD, but the diagnosis of AOSD was missed during his first presentation. In the second flaring episode, the diagnosis of AOSD was established. He had an excellent therapeutic response to anakinra and prednisone during the acute flaring episode. He is currently in complete remission on methotrexate as maintenance therapy. PMID:28690954

Emergency centre investigation of first-onset seizures in adults in the Western Cape, South Africa.

PubMed

Smith, A B; Van Hoving, D J; Wallis, L A

2013-08-21

Patients with first-onset seizures commonly present to emergency centres (ECs). The differential diagnosis is broad, potentially life-threatening conditions need to be excluded, and these patients need to be correctly diagnosed and appropriately referred. There are currently no data on adults presenting with first-onset seizures to ECs in South Africa. To review which investigations were performed on adults presenting with first-onset seizures to six ECs in the Western Cape Province. A prospective, cross-sectional study was conducted from 1 July 2011 to 31 December 2011. All adults with first-onset seizures were included; children and trauma patients were excluded. Subgroup analyses were conducted regarding HIV status and inter-facility variation. A total of 309 patients were included. Computed tomography (CT) scans were planned in 218 (70.6%) patients, but only performed in 169; 96 (56.8%) showed abnormalities judged to be causative (infarction, intracerebral haemorrhage and atrophy being the most common). At least 80% of patients (n=247) received a full renal and electrolyte screen, blood glucose testing and a full haematological screen. Lumbar puncture (LP) was performed in 67 (21.7%) patients, with normal cerebrospinal fluid findings in 51 (76.1%). Only 27 (8%) patients had an electroencephalogram, of which 5 (18%) were abnormal. There was a statistically significant difference in the number of CT scans (p=0.002) and LPs (p<0.001) performed in the HIV-positive group (n=49). This study demonstrated inconsistency and wide local variance for all types of investigations done. It emphasises the need for a local guideline to direct doctors to appropriate investigations, ensuring better quality patient care and potential cost-saving.

Clinical features and long-term outcomes of systemic lupus erythematosus: comparative data of childhood, adult and late-onset disease in a national register.

PubMed

Sousa, S; Gonçalves, M J; Inês, L S; Eugénio, G; Jesus, D; Fernandes, S; Terroso, G; Romão, V C; Cerqueira, M; Raposo, A; Couto, M; Nero, P; Sequeira, G; Nóvoa, T; Melo Gomes, J A; da Silva, J Canas; Costa, L; Macieira, C; Silva, C; Silva, J A P; Canhão, H; Santos, M J

2016-07-01

Systemic lupus erythematosus (SLE) affects predominantly women at reproductive age but may present at any age. Age at disease onset has a modulating effect on presentation and course of disease, but controversies persist regarding its impact on long-term outcome. Our aims were to characterize clinical features, co-morbidities and cumulative damage in childhood-onset, adult-onset and late-onset SLE. Patients with childhood-onset SLE fulfilling ACR 1997 criteria were identified in a nationwide register-Reuma.pt/SLE (N = 89) and compared with adult-onset and late-onset counterparts matched 1:1:1 for disease duration. 267 SLE patients with mean disease duration of 11.9 ± 9.3 years were analyzed. Skin (62 %), kidney (58 %), neurological (11 %) and hematologic involvement (76 %) were significantly more common in childhood-onset SLE and disease activity was higher in this subset than in adult- and late-onset disease (SLEDAI-2K 3.4 ± 3.8 vs. 2.2 ± 2.7 vs. 1.6 ± 2.8, respectively; p = 0.004). Also, more childhood-onset patients received cyclophosphamide (10 %) and mycophenolate mofetil (34 %). A greater proportion of women (96 %), prevalence of arthritis (89 %) and anti-SSA antibodies (34 %) were noted in the adult-onset group. There was a significant delay in the diagnosis of SLE in older ages. Co-morbidities such as hypertension, diabetes and thyroid disease were significantly more frequent in late-onset SLE, as well as the presence of irreversible damage evaluated by the SLICC/ACR damage index (20 vs. 26 vs. 40 %; p < 0.001). Greater organ involvement as well as the frequent need for immunosuppressants supports the concept of childhood-onset being a more severe disease. In contrast, disease onset is more indolent but co-morbidity burden and irreversible damage are greater in late-onset SLE, which may have implications for patients' management.

Mechanisms of diarrhoea in myotonic dystrophy.

PubMed

Rönnblom, A; Andersson, S; Danielsson, A

1998-07-01

Gastrointestinal (GI) symptoms are common in myotonic dystrophy (MD). Diarrhoea is one of the more disabling of these GI complaints. The mechanisms behind diarrhoea in MD have not previously been investigated systematically. To elucidate the mechanisms behind diarrhoea in MD. Twenty patients with MD and suffering from diarrhoea were investigated in order to detect malabsorption (blood tests and faecal fat excretion) and bile acid malabsorption ([75Se]selenahomocholic acid-taurine (SeHCAT) retention) and to study intestinal morphology (duodenal and rectal biopsies). Two patients had deficiency of folic acid and four showed reduced levels of pancreatic isoamylase, but none of them had steatorrhoea. Two out of eight patients had abnormal bile acid breath tests with normal SeHCAT, indicating small bowel bacterial overgrowth and 12 displayed reduced SeHCAT retention. Duodenal biopsies were normal in eight patients and five out of nine rectal biopsies displayed slight inflammation. A possible mechanism of diarrhoea in MD could be identified in most of the patients. Bile acid malabsorption seems to be a frequent cause and can be treated successfully.

Adult-Onset Still Disease

PubMed Central

Gerfaud-Valentin, Mathieu; Maucort-Boulch, Delphine; Hot, Arnaud; Iwaz, Jean; Ninet, Jacques; Durieu, Isabelle; Broussolle, Christiane; Sève, Pascal

2014-01-01

Abstract We conducted a retrospective observational study to describe a cohort and identify the prognostic factors in adult-onset Still disease (AOSD). Patients enrolled in this retrospective chart review fulfilled either Yamaguchi or Fautrel criteria. Candidate variables were analyzed with logistic unadjusted and adjusted regression models. Fifty-seven patients were seen in the internal medicine (75%) and rheumatology (25%) departments over a mean period of 8.4 years. The median time to diagnosis was 4 months. The course of AOSD was monocyclic in 17 patients, polycyclic in 25, and chronic in 15. The assessment of glycosylated ferritin (GF) in 37 patients was correlated with early diagnosis. Nine 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) scans identified the lymph nodes and glands as the main sites of hypermetabolism. Complications were frequent (n = 19), including reactive hemophagocytic syndrome (n = 8). None of the 3 deaths could be attributed to AOSD. Corticosteroid dependence, as predicted by a low GF level, occurred in 23 patients (45%). A quarter of the patients received tumor necrosis factor-α blockers or anakinra with good tolerance. Fever >39.5°C was predictive of monocyclic AOSD, while arthritis and thrombocytopenia were associated with chronic and complicated AOSD, respectively. The youngest patients had the highest risks of resistance to first-line treatments. AOSD remains difficult to diagnose. Mortality is low despite frequent complications. GF and 18FDG-PET scans were of value in the diagnostic approach. The condition in highly symptomatic patients evolved to systemic AOSD, whereas more progressive patterns with arthritis predicted chronic AOSD. PMID:24646465

Social outcomes of young adults with childhood-onset epilepsy: A case-sibling-control study.

PubMed

Baca, Christine B; Barry, Frances; Vickrey, Barbara G; Caplan, Rochelle; Berg, Anne T

2017-05-01

We aimed to compare long-term social outcomes in young adults with childhood-onset epilepsy (cases) with neurologically normal sibling controls. Long-term social outcomes were assessed at the 15-year follow-up of the Connecticut Study of Epilepsy, a community-based prospective cohort study of children with newly diagnosed epilepsy. Young adults with childhood-onset epilepsy with complicated (abnormal neurologic exam findings, abnormal brain imaging with lesion referable to epilepsy, intellectual disability (ID; IQ < 60) or informative history of neurologic insults to which the occurrence of epilepsy might be attributed), and uncomplicated epilepsy presentations were compared to healthy sibling controls. Age, gender, and matched-pair adjusted generalized linear models stratified by complicated epilepsy and 5-year seizure-free status estimated adjusted odds ratios (aORs) and 95% confidence intervals [CIs] for each outcome. The 15-year follow-up included 361 individuals with epilepsy (59% of initial cases; N = 291 uncomplicated and N = 70 complicated epilepsy; mean age 22 years [standard deviation, SD 3.5]; mean epilepsy onset 6.2 years [SD 3.9]) and 173 controls. Social outcomes for cases with uncomplicated epilepsy with ≥5 years terminal remission were comparable to controls; cases with uncomplicated epilepsy <5 years seizure-free were more likely to be less productive (school/employment < 20 h/week) (aOR 3.63, 95% CI 1.83-7.20) and not to have a driver's license (aOR 6.25, 95% CI 2.85-13.72). Complicated cases with epilepsy <5 years seizure-free had worse outcomes across multiple domains; including not graduating high school (aOR 24.97, 95% CI 7.49-83.30), being un- or underemployed (<20 h/week) (aOR 11.06, 95% CI 4.44-27.57), being less productively engaged (aOR 15.71, 95% CI 6.88-35.88), and not living independently (aOR 10.24, 95% CI 3.98-26.36). Complicated cases without ID (N = 36) had worse outcomes with respect to productive engagement (aOR 6.02; 95% CI 2

Social outcomes of young adults with childhood-onset epilepsy: a case-sibling-control study

PubMed Central

Baca, Christine B.; Barry, Frances; Vickrey, Barbara G.; Caplan, Rochelle; Berg, Anne T.

2017-01-01

Objective We aimed to compare long-term social outcomes in young adults with childhood-onset epilepsy (cases) with neurologically normal sibling controls. Methods Long-term social outcomes were assessed at the 15-year follow-up of the Connecticut Study of Epilepsy, a community-based prospective cohort study of children with newly diagnosed epilepsy. Young adults with childhood-onset epilepsy with complicated (abnormal neurological exam, abnormal brain imaging with lesion referable to epilepsy, intellectual disability (ID; IQ<60) or informative history of neurological insults to which the occurrence of epilepsy might be attributed), and uncomplicated epilepsy presentations were compared to healthy sibling controls. Age, gender and matched-pair adjusted generalized linear models stratified by complicated epilepsy and 5-year seizure-free status estimated adjusted odds ratios (aORs) and 95% CI’s for each outcome. Results The 15-year follow-up included 361 individuals with epilepsy (59% of initial cases; N=291 uncomplicated and N=70 complicated epilepsy; mean age 22 years (SD=3.5); mean epilepsy onset 6.2 years (SD=3.9)) and 173 controls. Social outcomes for cases with uncomplicated epilepsy with ≥5-years terminal remission were comparable to controls; cases with uncomplicated epilepsy <5-years seizure-free were more likely to be less productive (school/employment <20 hrs/wk) (aOR 3.63, 95% CI 1.83–7.20) and not to have a driver’s license (aOR 6.25, 95% CI 2.85–13.72). Complicated cases with epilepsy <5 years seizure-free had worse outcomes across multiple domains; including not graduating high school (aOR 24.97, 95% CI 7.49–83.30), being un- or underemployed (<20 hrs/wk) (aOR 11.06, 95% CI 4.44–27.57), being less productively engaged (aOR 15.71, 95% CI 6.88–35.88) and not living independently (aOR 10.24, 95% CI 3.98–26.36). Complicated cases without ID (N=36) had worse outcomes with respect to productive engagement (aOR 6.02; 95% CI 2.48–14

Validation of DSM-5 age-of-onset criterion of attention deficit/hyperactivity disorder (ADHD) in adults: Comparison of life quality, functional impairment, and family function.

PubMed

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

2015-12-01

The newly published Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) elevates the threshold of the ADHD age-of-onset criterion from 7 to 12 years. This study evaluated the quality of life and functional impairment of adults with ADHD who had symptoms onset by or after 7 years and examined the mediation effect of family function and anxiety/depression symptoms between ADHD diagnosis and quality of life and functional impairment. We assessed 189 adults with ADHD and 153 non-ADHD controls by psychiatric interview and self-administered reports on the Adult ADHD Quality of Life Scale, Weiss Functional Impairment Rating Scale, Family APGAR, and Adult Self Report Inventory-4. The ADHD group was divided into early-onset ADHD (onset <7 years, n=147) and late-onset ADHD (onset between 7 and 12 years, n=42). The mediation analysis was conducted to verify the mediating factors from ADHD to functional impairment and quality of life. The late-onset ADHD had more severe functional impairment at work and poorer family support than early-onset ADHD while they had comparable impairment at other domains. Less perceived family support and current anxiety/depressive symptoms partially mediated the link between ADHD diagnosis and quality of life/functional impairment both in early- and late-onset ADHD. Our data support decreased quality of life and increased functional impairment in adult ADHD, regardless of age of onset, and these adverse outcomes may be mediated by family support and anxiety/depression at adulthood. Our findings also imply that the new DSM-5 ADHD criteria do not over-include individuals without impairment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Induction and reversal of myotonic dystrophy type 1 pre-mRNA splicing defects by small molecules.

PubMed

Childs-Disney, Jessica L; Stepniak-Konieczna, Ewa; Tran, Tuan; Yildirim, Ilyas; Park, HaJeung; Chen, Catherine Z; Hoskins, Jason; Southall, Noel; Marugan, Juan J; Patnaik, Samarjit; Zheng, Wei; Austin, Chris P; Schatz, George C; Sobczak, Krzysztof; Thornton, Charles A; Disney, Matthew D

2013-01-01

The ability to control pre-mRNA splicing with small molecules could facilitate the development of therapeutics or cell-based circuits that control gene function. Myotonic dystrophy type 1 is caused by the dysregulation of alternative pre-mRNA splicing due to sequestration of muscleblind-like 1 protein (MBNL1) by expanded, non-coding r(CUG) repeats (r(CUG)(exp)). Here we report two small molecules that induce or ameliorate alternative splicing dysregulation. A thiophene-containing small molecule (1) inhibits the interaction of MBNL1 with its natural pre-mRNA substrates. Compound (2), a substituted naphthyridine, binds r(CUG)(exp) and displaces MBNL1. Structural models show that 1 binds MBNL1 in the Zn-finger domain and that 2 interacts with UU loops in r(CUG)(exp). This study provides a structural framework for small molecules that target MBNL1 by mimicking r(CUG)(exp) and shows that targeting MBNL1 causes dysregulation of alternative splicing, suggesting that MBNL1 is thus not a suitable therapeutic target for the treatment of myotonic dystrophy type 1.

Longitudinal Changes in White Matter Fractional Anisotropy in Adult-Onset Niemann-Pick Disease Type C Patients Treated with Miglustat.

PubMed

Bowman, Elizabeth A; Velakoulis, Dennis; Desmond, Patricia; Walterfang, Mark

2018-01-01

Niemann-Pick disease type C (NPC) is a rare neurometabolic disorder resulting in impaired intracellular lipid trafficking. The only disease-modifying treatment currently available is miglustat, an iminosugar that inhibits the accumulation of lipid metabolites in neurons and other cells. This longitudinal diffusion tensor imaging (DTI) study examined how the rate of white matter change differed between treated and non-treated adult-onset NPC patient groups. Nine adult-onset NPC patients (seven undergoing treatment with miglustat, two not treated) underwent DTI neuroimaging. Rates of change in white matter structure as indexed by Tract-Based Spatial Statistics (TBSS) of fractional anisotropy were compared between treated and untreated patients. Treated patients were found to have a significantly slower rate of white matter change in the corticospinal tracts, the thalamic radiation and the inferior longitudinal fasciculus. This is further evidence that miglustat treatment may have a protective effect on white matter structure in the adult-onset form of the disease.

Career readiness, developmental work personality and age of onset in young adult central nervous system survivors.

PubMed

Strauser, David; Wagner, Stacia; Wong, Alex W K; O'Sullivan, Deidre

2013-04-01

The primary purpose of this paper is to undertake foundational research in the area of career readiness, work personality and age of onset with young adult central nervous system (CNS) survivors. Participants for this study consisted of 43 individuals whose age range from 18 to 30 (M = 21.64, SD = 3.46), an average age of brain tumor onset of 9.50 years (SD = 4.73) and average years off of treatment of 7.25 years (SD = 5.80). Packets were distributed to survivors who were participating in a psychosocial cancer treatment program. Participants completed multiple career instruments and a demographic form. Differences between groups and among the variables were examined and size effect sizes were analyzed. Young adult CNS survivors had significantly lower levels of work personality and career readiness when compared to young adult non-cancer survivors with CNS cancer with those between the ages of 6 and 12 reported significantly lower levels when compared to individuals diagnosed before age 6 and after the age of 13. Young adult CNS survivors at an increased risk for having lower levels of work personality and career readiness then a norm group comparison. Age of onset (between 6 and 12) may be at significant risk factor for developing poor or dysfunctional work and career behaviors. • Young adults with central nervous system (CNS) cancer are at particular risk for experiencing difficulties related to career and employment. • Work personality and career readiness are two constructs that have been found to be related to one's ability to meet the demands of work. • Young adult CNS cancer survivors have lower levels of work personality and career readiness. • Individuals diagnosed between the ages of 6 and 12 may be at particular risk and may need specific vocational rehabilitation interventions. • The results of this study point to the need for comprehensive career and vocational services for young adult CNS cancer survivors.

A longitudinal study of adult-onset asthma incidence among HMO members

PubMed Central

Sama, Susan R; Hunt, Phillip R; Cirillo, CIH Priscilla; Marx, Arminda; Rosiello, Richard A; Henneberger, Paul K; Milton, Donald K

2003-01-01

Background HMO databases offer an opportunity for community based epidemiologic studies of asthma incidence, etiology and treatment. The incidence of asthma in HMO populations and the utility of HMO data, including use of computerized algorithms and manual review of medical charts for determining etiologic factors has not been fully explored. Methods We identified adult-onset asthma, using computerized record searches in a New England HMO. Monthly, our software applied exclusion and inclusion criteria to identify an "at-risk" population and "potential cases". Electronic and paper medical records from the past year were then reviewed for each potential case. Persons with other respiratory diseases or insignificant treatment for asthma were excluded. Confirmed adult-onset asthma (AOA) cases were defined as those potential cases with either new-onset asthma or reactivated mild intermittent asthma that had been quiescent for at least one year. We validated the methods by reviewing charts of selected subjects rejected by the algorithm. Results The algorithm was 93 to 99.3% sensitive and 99.6% specific. Sixty-three percent (n = 469) of potential cases were confirmed as AOA. Two thirds of confirmed cases were women with an average age of 34.8 (SD 11.8), and 45% had no evidence of previous asthma diagnosis. The annualized monthly rate of AOA ranged from 4.1 to 11.4 per 1000 at-risk members. Physicians most commonly attribute asthma to infection (59%) and allergy (14%). New-onset cases were more likely attributed to infection, while reactivated cases were more associated with allergies. Medical charts included a discussion of work exposures in relation to asthma in only 32 (7%) cases. Twenty-three of these (72%) indicated there was an association between asthma and workplace exposures for an overall rate of work-related asthma of 4.9%. Conclusion Computerized HMO records can be successfully used to identify AOA. Manual review of these records is important to confirm case

Onset aging conditions of adults with an intellectual disability associated with primary caregiver depression.

PubMed

Lin, Lan-Ping; Hsu, Shang-Wei; Kuo, Meng-Ting; Wu, Jia-Lin; Chu, Cordia; Lin, Jin-Ding

2014-03-01

Caregivers of adults with an intellectual disability experience depressive symptoms, but the aging factors of the care recipients associated with the depressive symptoms are unknown. The objective of this study was to analyze the onset aging conditions of adults with an intellectual disability that associated with the depression scores of their primary caregivers. A cross-sectional survey was administered to gather information from 455 caregivers of adults with an intellectual disability about their symptoms of depression which assessed by a 9-item Patient Health Questionnaire (PHQ-9). The 12 aging conditions of adults with an intellectual disability include physical and mental health. The results indicate that 78% of adults with an intellectual disability demonstrate aging conditions. Physical conditions associated with aging include hearing decline (66.3%), vision decline (63.6%), incontinence (44%), articulation and bone degeneration (57.9%), teeth loss (80.4), physical strength decline (81.2%), sense of taste and smell decline (52.8%), and accompanied chronic illnesses (74.6%). Mental conditions associated with aging include memory loss (77%), language ability deterioration (74.4%), poor sleep quality (74.2%), and easy onset of depression and sadness (50.3%). Aging conditions of adults with an intellectual disability (p<0.001) was one factor that significantly affected the presence of depressive symptom among caregivers after controlling demographic characteristics. Particularly, poor sleep quality of adults with an intellectual disability (yes vs. no, OR=3.807, p=0.002) was statistically correlated to the occurrence of significant depressive symptoms among their caregivers. This study suggests that the authorities should reorient community services and future policies toward the needs of family caregivers to decrease the burdens associated with caregiving. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Adult-onset Still's disease with pulmonary and cardiac involvement and response to intravenous immunoglobulin].

PubMed

Neto, Nilton Salles Rosa; Waldrich, Leandro; de Carvalho, Jozélio Freire; Pereira, Rosa Maria Rodrigues

2009-01-01

Cardiopulmonary manifestations of adult-onset Still's disease (AOSD) include pericarditis, pleural effusion, transient pulmonary infiltrates, pulmonary interstitial disease and myocarditis. Serositis are common but pneumonitis and myocarditis are not and bring elevated risk of mortality. They may manifest on disease onset or flares. Previously reported cases were treated with high-dose glucocorticoids and immunosupressants and, when refractory, intravenous immunoglobulin (IVIG). We report an AOSD patient whose flare presented with severe pleupneumonitis and myopericarditis and, following nonresponse to a methylprednisolone pulse, high dose of prednisone and cyclosporine A, recovered after a 2-day 1g/kg/day IVIG infusion.

Preferential Nucleosome Assembly at DNA Triplet Repeats from the Myotonic Dystrophy Gene

NASA Astrophysics Data System (ADS)

Wang, Yuh-Hwa; Amirhaeri, Sorour; Kang, Seongman; Wells, Robert D.; Griffith, Jack D.

1994-07-01

The expansion of CTG repeats in DNA occurs in or near genes involved in several human diseases, including myotonic dystrophy and Huntington's disease. Nucleosomes, the basic structural element of chromosomes, consist of 146 base pairs of DNA coiled about an octamer of histone proteins and mediate general transcriptional repression. Electron microscopy was used to examine in vitro the nucleosome assembly of DNA containing repeating CTG triplets. The efficiency of nucleosome formation increased with expanded triplet blocks, suggesting that such blocks may repress transcription through the creation of stable nucleosomes.

Diabetes distress in adult type 1 diabetes mellitus men and women with disease onset in childhood and in adulthood.

PubMed

Lašaitė, Lina; Ostrauskas, Rytas; Žalinkevičius, Rimantas; Jurgevičienė, Nijolė; Radzevičienė, Lina

2016-01-01

To determine whether or not diabetes distress varies by age of type 1 diabetes mellitus (T1DM) onset and/or gender. A total of 700 adult T1DM patients were randomly selected from the Lithuanian Diabetes Registry; 214 of them (30.6%) agreed to participate and were recruited for the study. Diabetes distress (emotional burden, physician-related distress, regimen-related distress, interpersonal distress) was compared in 105 (42 men and 63 women) patients with T1DM diagnosed during 0-18years of life, and in 109 (61 men and 48 women) with T1DM diagnosed in adulthood, using Diabetes Distress Scale (DDS). Adult childhood-onset T1DM women have higher regimen-related distress (36.3±21.3 vs 26.6±16.2, p=0.016) than adulthood-onset women. Adult childhood-onset T1DM women experience higher diabetes distress (higher emotional burden (27.0±22.0 vs 15.6±16.4, p=0.006), physician-related distress (34.4±33.9 vs 20.7±29.4, p=0.024), total diabetes distress (41.2±13.6 vs 34.8±10.9, p=0.011)) than childhood-onset men. Adulthood-onset T1DM women experience higher physician-related distress (39.2±37.6 vs 23.4±32.5, p=0.013), but lower regimen-related distress (26.6±16.2 vs 35.8±21.6, p=0.014) than adulthood-onset men. In conclusion our findings reinforce the interdependence of psychological and biomedical factors in influencing health outcomes and support the need to provide psychological assessment and support to patients with T1DM. Copyright © 2016 Elsevier Inc. All rights reserved.

Life satisfaction in adults with pediatric-onset spinal cord injuries.

PubMed

Anderson, Caroline J; Krajci, Katherine A; Vogel, Lawrence C

2002-01-01

To determine the level of life satisfaction of adults with pediatric-onset spinal cord injuries (SCI) and the factors associated with life satisfaction. A structured interview including standardized measures. Participants were individuals who sustained SCI at age 18 years or younger, were 24 years of age or olderat interview, did not have significant brain injury, and were living in the United States or Canada. A structured interview, the Functional Independence Measure (FIM), the Craig Handicap Assessment and Reporting Technique (CHART), the Short-Form 12 (SF-12), and the Satisfaction with Life Scale (SWLS). Two hundred sixteen individuals were interviewed. Mean age at injury was 1 4 years, mean age at interview was 29 years, and mean duration of injury was 14 years. The mean SWLS score was 23.6, and the median score was 25. There was not a significant difference between men and women, but those with tetraplegia were significantly less satisfied than were those with paraplegia. A regression model identified age at injury, community mobility (CHART), marital status, use of street drugs, perceived mental health (SF-12), and medical complications as predictors of life satisfaction. Other factors strongly associated with SWLS were employment, income, independent living, FIM total plus physical and sociocognitive domain scores, perceived physical health (SF-12), and CHART total plus the subscales of physical independence, cognitive independence, and occupation. Life satisfaction in adults with pediatric-onset SCI is associated with demographic, injury-related, and functional limitation factors, as well as with health status and community integration outcomes.

Adult-onset minimal change disease among Taiwanese: clinical features, therapeutic response, and prognosis.

PubMed

Huang, J J; Hsu, S C; Chen, F F; Sung, J M; Tseng, C C; Wang, M C

2001-01-01

There are some racial differences in the prevalence and prognosis of idiopathic nephrotic syndrome; however, reports about minimal change disease (MCD) in Chinese were rare. We retrospectively analyzed 123 Chinese adults with idiopathic nephrotic syndrome, who received percutaneous renal biopsy in our institution within the last 10 years. In total, 46 patients (37.4%) were compatible with the pathological diagnosis of MCD. The male to female ratio was 1.2:1. The mean age of onset was 30.9 years, and 80% of the patients with MCD were less than 40 years. The mean daily proteinuria was 10.2 g, and serum albumin was 1.8 mg/dl. Azotemia occurred in 16 (35%) of 46 cases; hypertension, 13%; and microscopic hematuria, 13%. High selectivity index for proteinuria (SI <0.1) was noted in 12 (39%) of 31 cases; and high IgE level was found in 83.7% of the study subjects, although only one case had allergic history. Complete remission in 36 MCD patients treated with corticosteroid was achieved by 42% (15/36), 80% (29/36), and 94% (34/36) within 4, 8, and 12 weeks, respectively. The time interval to remission was similar between the younger group (<40 years old, 1.7 months) and older group (>40 years old, 1.6 months). Nineteen (56%) of 34 cases with steroid response did not relapse, and the other cases (44%) had a mean relapse rate of 1.5 times per patient within a period of 45 months. The age of onset in MCD cases was not significantly correlated with steroid-responsive rate, and the time interval to remission. However, a tendency existed between the onset in the young age and the sequentially relapsing rate (p = 0.06). Two cases with primary steroid resistance and 5 cases with frequent relapse or steroid dependence responded well to intravenous pulse therapy of cyclophosphamide, except one refractory case. No thrombotic episode was ever noted in our group. Regarding infectious complications, primary peritonitis occurred in one, pneumonia in one, and cellulitis in 6 cases during

Body weight status and onset of cognitive impairment among U.S. middle-aged and older adults.

PubMed

Xiang, Xiaoling; An, Ruopeng

2015-01-01

To examine the relationship between body weight status and onset of cognitive impairment among U.S. middle-aged and older adults. Study sample came from 1996 to 2010 waves of the Health and Retirement Study, consisting of 6739 community-dwelling adults born between 1931 and 1941 who were free from cognitive impairment in 1996. Body mass index (BMI) was calculated from self-reported height/weight. Cognitive impairment was defined by a composite score of 11 or lower on the immediate and delayed word recall, serial 7's, and backwards counting tests. Kaplan-Meier estimator and Cox proportional hazards model were performed to examine the association between base-year body weight status and future onset of cognitive impairment. Compared with their normal weight counterparts, the unadjusted hazard ratio (HR) for cognitive impairment incidence was 2.03 (95% confidence interval: 1.38-3.00), 1.15 (1.02-1.29), 1.28 (1.14-1.43), and 1.59 (1.33-1.92) among underweight (BMI<18.5), overweight (25 ≤ BMI < 30), class I obese (30 ≤ BMI < 35), and class II obese or above (BMI ≥ 35) participants, respectively. The unadjusted relationship between obesity and cognitive impairment onset appeared stronger among females than among males. After adjusting for base-year individual sociodemographics, functional limitations and chronic conditions, the estimated associations between body weight status and cognitive impairment were attenuated but remained statistically significant for underweight participants. Underweight is a robust risk factor for onset of cognitive impairment in later life. Weight management programs targeting middle-aged and older adults should focus on achieving and maintaining optimal body weight. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Childhood exposure to infection and risk of adult onset wheeze and atopy.

PubMed

Bodner, C; Anderson, W J; Reid, T S; Godden, D J

2000-05-01

The prevalence of asthma and allergic diseases in children and young adults is inversely associated with family size. It has been suggested that more frequent exposure to infections in a large family group, particularly those spread by the faecal-oral route, may protect against atopic diseases, although not all published data support this hypothesis. Whether similar considerations apply to adult onset wheeze is unknown. The relationship between adult onset wheezing and atopy measured in adulthood and childhood exposure to a range of infections was investigated. A nested case control study of participants in a 30 year follow up survey was conducted. Questionnaire data on childhood infections had been obtained in a 1964 survey. In 1995 a further questionnaire on respiratory symptoms and other risk factors for wheezing illness was administered, total IgE, skin and RAST tests were performed, and serum was stored. In 1999 serological tests for hepatitis A, Helicobacter pylori, and Toxoplasma gondii were performed on the stored samples. Information from the 1964 questionnaires was available for 97 cases and 208 controls and serological tests were obtained for 85 cases and 190 controls. The potential risk factors were examined for all cases, those who reported doctor diagnosed asthma, those who described persistent cough and phlegm with wheeze, and subjects stratified by atopic status. The sibship structure was similar in cases and controls. In univariate analysis of all cases, childhood infections reported by parents as acquired either before or after the age of three years did not influence case:control or atopic status. Seropositivity was also similar for all cases and controls, but cases in the subgroup with chronic cough and phlegm were more likely to be seropositive for hepatitis A and H pylori. Seropositivity was unrelated to atopic status. In multivariate analyses both the effect of having two or more younger siblings (OR 0.1, 95% CI 0.03 to 0.8) and of acquiring

Impacts of age of onset of substance use disorders on risk of adult incarceration among disadvantaged urban youth: a propensity score matching approach.

PubMed

Slade, Eric P; Stuart, Elizabeth A; Salkever, David S; Karakus, Mustafa; Green, Kerry M; Ialongo, Nicholas

2008-05-01

Age of onset of substance use disorders in adolescence and early adulthood could be associated with higher rates of adult criminal incarceration in the U.S., but evidence of these associations is scarce. Propensity score matching was used to estimate the association between adolescent-onset substance use disorders and the rate of incarceration, as well as incarceration costs and self-reported criminal arrests and convictions, of young men predominantly from African American, lower income, urban households. Age of onset was differentiated by whether onset of the first disorder occurred by age 16. Onset of a substance use disorder by age 16, but not later onset, was associated with a fourfold greater risk of adult incarceration for substance related offenses as compared to no disorder (0.35 vs. 0.09, P=0.044). Onset by age 16 and later onset were both positively associated with incarceration costs and risk of arrest and conviction, though associations with crime outcomes were more consistent with respect to onset by age 16. Results were robust to propensity score adjustment for observable predictors of substance use in adolescence and involvement in crime as an adult. Among young men in this high risk minority sample, having a substance use disorder by age 16 was associated with higher risk of incarceration for substance related offenses in early adulthood and with more extensive criminal justice system involvement as compared to having no disorder or having a disorder beginning at a later age.

The Onset of Depression During the Great Recession: Foreclosure and Older Adult Mental Health

PubMed Central

Cagney, Kathleen A.; Browning, Christopher R.; Iveniuk, James; English, Ned

2014-01-01

Objectives. We examined neighborhood-level foreclosure rates and their association with onset of depressive symptoms in older adults. Methods. We linked data from the National Social Life, Health, and Aging Project (2005–2006 and 2010–2011 waves), a longitudinal, nationally representative survey, to data on zip code–level foreclosure rates, and predicted the onset of depressive symptoms using logit-linked regression. Results. Multiple stages of the foreclosure process predicted the onset of depressive symptoms, with adjustment for demographic characteristics and changes in household assets, neighborhood poverty, and visible neighborhood disorder. A large increase in the number of notices of default (odds ratio [OR] = 1.75; 95% confidence interval [CI] = 1.14, 2.67) and properties returning to ownership by the bank (OR = 1.62; 95% CI = 1.06, 2.47) were associated with depressive symptoms. A large increase in properties going to auction was suggestive of such an association (OR = 1.45; 95% CI = 0.96, 2.19). Age, fewer years of education, and functional limitations also were predictive. Conclusions. Increases in neighborhood-level foreclosure represent an important risk factor for depression in older adults. These results accord with previous studies suggesting that the effects of economic crises are typically first experienced through deficits in emotional well-being. PMID:24446830

Longitudinal employment outcomes in adults with pediatric-onset spinal cord injury.

PubMed

Hwang, M; Zebracki, K; Chlan, K M; Vogel, L C

2014-06-01

Longitudinal survey. To determine in adults with pediatric-onset spinal cord injury (SCI) employment outcomes, longitudinal changes in employment over time and changes in psychosocial outcomes associated with employment status. Community setting. Adults who had sustained a SCI before 19 years of age and had completed at least three consecutive annual interviews were included in the study. Generalized estimating equation models were formulated to obtain odds ratio (OR) of change in employment status and outcomes over time. Total 1691 interviews were conducted in 283 participants, 182 men and 101 women (88% Caucasian; age at baseline, 27.3±3.7 years; duration at baseline, 12.7±5.0 years). At the last interview (age, 34.4±5.2 years; duration, 19.9±6.1 years), 49.5% were employed and 47.0% had a baccalaureate or post-baccalaureate degree. There was no significant change in employment status over time (OR 1.01, confidence interval (CI) 0.98-1.04). Odds of employment increased over time in participants who were women (1.04, CI 1.00-1.08), married (1.05, CI 1.02-1.08) and attained baccalaureate (1.03, CI 1.00-1.07) or post-baccalaureate (1.05, CI 1.02-1.08) degree. Employment odds decreased with occurrence of autonomic dysreflexia (0.80, CI 0.65-0.99), spasticity (0.80, CI 0.59-0.99) or chronic medical condition (0.83, CI 0.71-0.98). Life satisfaction scores increased over time in those who remained employed (1.11, CI 1.01-1.22); odds of depression increased over time in those who remained unemployed (1.13, CI 1.04-1.23). Employment status remained relatively stable in adults with pediatric-onset SCI; however, changes in employment were associated with education, secondary health conditions and psychosocial well-being.

Chinese new immigrant mothers' perception about adult-onset non-communicable diseases prevention during childhood.

PubMed

Wang, Linda Dong Ling; Lam, Wendy Wing Tak; Wu, Joseph Tsz Kei; Fielding, Richard

2015-12-01

Many non-communicable diseases (NCDs) are largely preventable via behaviour change and healthy lifestyle, which may be best established during childhood. This study sought insights into Chinese new immigrant mothers' perceptions about adult-onset NCDs prevention during childhood. Twenty-three semi-structured interviews were carried out with new immigrant mothers from mainland China who had at least one child aged 14 years or younger living in Hong Kong. Interviews were audio taped, transcribed and analysed using a Grounded Theory approach. The present study identified three major themes: perceived causes of adult NCDs, beliefs about NCDs prevention and everyday health information practices. Unhealthy lifestyle, contaminated food and environment pollution were perceived as the primary causes of adult NCDs. Less than half of the participants recognized that parents had responsibility for helping children establish healthy behaviours from an early age to prevent diseases in later life. Most participants expressed helplessness about chronic diseases prevention due to lack of knowledge of prevention, being perceived as beyond individual control. Many participants experienced barriers to seeking health information, the most common sources of health information being interpersonal conversation and television. Participants' everyday information practice was passive and generally lacked awareness regarding early prevention of adult-onset NCDs. Updated understanding of this issue has notable implications for future health promotion interventions. © The Author (2014). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Epigenetic transgenerational inheritance of vinclozolin induced mouse adult onset disease and associated sperm epigenome biomarkers.

PubMed

Guerrero-Bosagna, Carlos; Covert, Trevor R; Haque, Md M; Settles, Matthew; Nilsson, Eric E; Anway, Matthew D; Skinner, Michael K

2012-12-01

The endocrine disruptor vinclozolin has previously been shown to promote epigenetic transgenerational inheritance of adult onset disease in the rat. The current study was designed to investigate the transgenerational actions of vinclozolin on the mouse. Transient exposure of the F0 generation gestating female during gonadal sex determination promoted transgenerational adult onset disease in F3 generation male and female mice, including spermatogenic cell defects, testicular abnormalities, prostate abnormalities, kidney abnormalities and polycystic ovarian disease. Pathology analysis demonstrated 75% of the vinclozolin lineage animals developed disease with 34% having two or more different disease states. Interestingly, the vinclozolin induced transgenerational disease was observed in the outbred CD-1 strain, but not the inbred 129 mouse strain. Analysis of the F3 generation sperm epigenome identified differential DNA methylation regions that can potentially be utilized as epigenetic biomarkers for transgenerational exposure and disease. Copyright © 2012 Elsevier Inc. All rights reserved.

Epigenetic Transgenerational Inheritance of Vinclozolin Induced Mouse Adult Onset Disease and Associated Sperm Epigenome Biomarkers

PubMed Central

Guerrero-Bosagna, Carlos; Covert, Trevor R.; Haque, Md. M.; Settles, Matthew; Nilsson, Eric E.; Anway, Matthew D.; Skinner, Michael K.

2012-01-01

The endocrine disruptor vinclozolin has previously been shown to promote epigenetic transgenerational inheritance of adult onset disease in the rat. The current study was designed to investigate the transgenerational actions of vinclozolin on the mouse. Transient exposure of the F0 generation gestating female during gonadal sex determination promoted transgenerational adult onset disease in F3 generation male and female mice, including spermatogenic cell defects, testicular abnormalities, prostate abnormalities, kidney abnormalities and polycystic ovarian disease. Pathology analysis demonstrated 75% of the vinclozolin lineage animals developed disease with 34% having two or more different disease states. Interestingly, the vinclozolin induced transgenerational disease was observed in the outbred CD-1 strain, but not the inbred 129 mouse strain. Analysis of the F3 generation sperm epigenome identified differential DNA methylation regions that can potentially be utilized as epigenetic biomarkers for transgenerational exposure and disease. PMID:23041264

Intrinsic development of choroidal and thalamic collaterals in hemorrhagic-onset moyamoya disease: case-control study of the Japan Adult Moyamoya Trial.

PubMed

Fujimura, Miki; Funaki, Takeshi; Houkin, Kiyohiro; Takahashi, Jun C; Kuroda, Satoshi; Tomata, Yasutake; Tominaga, Teiji; Miyamoto, Susumu

2018-05-04

OBJECTIVE This study was performed to identify the angiographic features of hemorrhagic-onset moyamoya disease (MMD) in comparison with those of patients with ischemic-onset MMD. METHODS This case-control study compared the data set of the Japan Adult Moyamoya (JAM) Trial with the angiographic data of adult patients with ischemic-onset MMD. The authors analyzed angiograms obtained at onset, classifying the collaterals into 3 subtypes: lenticulostriate anastomosis, thalamic anastomosis, and choroidal anastomosis. They then compared the extent of these collaterals, as indicated by the collateral development grade from 0 to 2 in each subtype, between the JAM Trial group and the ischemic-onset group. They also compared the involvement of the posterior cerebral artery (PCA) and Suzuki's angiographic staging between each group. RESULTS Among 89 ischemic-onset patients, 103 symptomatic hemispheres in 80 patients were analyzed and compared with 75 hemorrhagic hemispheres from the JAM Trial. The hemorrhagic-onset patients showed a significantly higher proportion of thalamic anastomosis (p = 0.043) and choroidal anastomosis (< 0.001), as indicated by grade 2 in each subtype, compared with ischemic-onset patients. Suzuki's angiographic staging was significantly higher in the hemorrhagic group (< 0.038). There was no difference in the extent of lenticulostriate anastomosis and PCA involvement between the groups. CONCLUSIONS In adult MMD, the characteristic pattern of the abnormal vascular networks at the base of the brain is different between each onset type. In light of the more prominent development of thalamic and choroidal anastomosis in the JAM Trial group in the present study, development of these collaterals, especially the choroidal collateral extending beyond the lateral ventricle, may play a critical role in hemorrhagic presentation in MMD. Clinical trial registration no. C000000166 ( http://www.umin.ac.jp/ctr/index.htm ).

Determinants of Social Outcomes in Adults With Childhood-onset Epilepsy

PubMed Central

Baca, Christine B.; Rychlik, Karen; Vickrey, Barbara G.; Caplan, Rochelle; Testa, Francine M.; Levy, Susan R.

2016-01-01

BACKGROUND: Adults with childhood-onset epilepsy experience poorer adult social outcomes than their peers. The relative roles of seizures over time versus learning and psychiatric problems are unclear. METHODS: We examined independent influences of psychiatric and learning disorders and of seizure course in 241 young adults (22–35 years old) with uncomplicated epilepsy in a longitudinal community-based cohort study. Social outcomes were ascertained throughout the study. A history of psychiatric and learning problems was ascertained ∼9 years after study entry. Seizure course was: “Excellent,” no seizures after the first year, in complete remission at last contact (N = 95, 39%); “Good,” seizures occurred 1 to 5 years after diagnosis, in complete remission at last contact (N = 56, 23%); “Fluctuating,” more complicated trajectories, but never pharmacoresistant (N = 70, 29%); “Pharmacoresistant,” long-term pharmacoresistant (N = 20, 8%). Multiple logistic regression was used to identify contributors to each social outcome. RESULTS: Better seizure course predicted college completion, being either employed or pursuing a degree, and driving, but was not substantially associated with other social outcomes. Poorer seizure course was associated with a greater likelihood of having offspring, particularly in women without partners. Learning problems, psychiatric disorders, or both negatively influenced all but 2 of the social outcomes. CONCLUSIONS: In young adults with uncomplicated epilepsy, the course of seizures contributed primarily to education, employment, and driving. A history of learning problems and psychiatric disorders adversely influenced most adult outcomes. These findings identify potential reasons for vocational and social difficulties encountered by young adults with childhood epilepsy and areas to target for counseling and transition planning. PMID:26983470

Early-Onset Psychoses: Comparison of Clinical Features and Adult Outcome in 3 Diagnostic Groups

ERIC Educational Resources Information Center

Ledda, Maria Giuseppina; Fratta, Anna Lisa; Pintor, Manuela; Zuddas, Alessandro; Cianchetti, Carlo

2009-01-01

A comparison of clinical features and adult outcome in adolescents with three types of psychotic disorders: schizophrenic (SPh), schizoaffective (SA) and bipolar with psychotic features (BPP). Subjects (n = 41) were finally diagnosed (DSM-IV criteria) with SPh (n = 17), SA (n = 11) or BPP (n = 13). Clinical evaluation took place at onset and at a…

The role of environmental factors for the onset of restricted mobility outside the home among older adults with osteoarthritis: a prospective cohort study

PubMed Central

Rantakokko, Merja; Wilkie, Ross

2017-01-01

Objectives The study examines how environmental factors contribute to the onset of restricted mobility outside the home among older adults with osteoarthritis. Methods This is a prospective cohort study of adults aged 50 years and older with osteoarthritis (n=1802). Logistic regression tested the association between the onset of restricted mobility outside the home and health, sociodemographic and perceived environmental barriers (hills and steep slopes, inaccessible public buildings, poor pavement condition, lack of access to public parks or sport facilities, heavy traffic or speeding cars and poor weather). The potential moderating role of environmental barriers on the association between health factors and onset was examined using interaction terms and stratified analysis. Results Of 1802 participants, 13.5% (n=243) reported the onset of restricted mobility outside the home at 3-year follow-up. Walking disability, anxiety, depression, cognitive impairment and obesity and all environmental barriers were associated with onset after adjustment for confounders. Environmental barriers had an added contribution to the effect of the health conditions on onset of restricted mobility, which was attenuated when adjusted for confounders. The added contribution remained only for walking disability and the presence of hills and steep slopes; in the presence of both, the association with onset of restricted mobility was stronger (OR 7.66, 95% CI 4.64 to 12.64) than in the presence of walking disability (3.60, 2.43 to 5.32) or the presence of hills and steep slopes alone (4.55, 2.89 to 7.16). Conclusion For older adults with osteoarthritis, environmental barriers are associated and add a contribution to that of morbidities and walking disability on the onset of restricted mobility outside the home. Awareness of environmental barriers is important when aiming to maintain mobility and activities outside the home despite health conditions in older adults. PMID:28667194

Socioeconomic factors do not but GH treatment does affect mortality in adult-onset growth hormone deficiency.

PubMed

Stochholm, Kirstine; Berglund, Agnethe; Juul, Svend; Gravholt, Claus Højbjerg; Christiansen, Jens S

2014-11-01

GH deficiency is associated with changes in body composition, increased cardiovascular risk markers, and reduced bone mineral density. There seem to be multiple causes of the reported increased morbidity and mortality. The objective was to study the socioeconomic status in patients with adult-onset GH deficiency and its impact on mortality. This is a nationwide registry study in which the socioeconomic status in adult-onset GH deficient patients was identified in the Danish registries and compared with controls matched on age and gender. The socio-economic status included cohabitation, education, income, parenthood, convictions, and retirement. All patients had adult-onset GH deficiency and were born between 1950 and 1980. Two-hundred seventy-six patients (53.6% men) and 25 717 controls were included. GH-treated patients had a reduced mortality in total and due to malignancy compared with untreated patients. This difference remained after adjustment for cohabitation and education. Compared with the background population, the incidence of cohabitation, parenthood, and convictions was significantly reduced in patients, whereas education was unaffected. Retirement was significantly increased. Mortality was increased in patients, especially among patients not treated with GH. In GH-treated patients, mortality was decreased in total and due to malignancy compared with untreated patients, even after adjustment for all possible measured confounders. The patients had an impaired socioeconomic profile on most parameters compared with controls. This study does not support the suggestion that GH replacement therapy causes increased mortality.

Variation in Genes Related to Cochlear Biology Is Strongly Associated with Adult-Onset Deafness in Border Collies

PubMed Central

Ruhe, Alison L.; Erdman, Carolyn A.; Robertson, Kathryn R.; Webb, Aubrey A.; Williams, D. Colette; Chang, Melanie L.; Hytönen, Marjo K.; Lohi, Hannes; Hamilton, Steven P.; Neff, Mark W.

2012-01-01

Domestic dogs can suffer from hearing losses that can have profound impacts on working ability and quality of life. We have identified a type of adult-onset hearing loss in Border Collies that appears to have a genetic cause, with an earlier age of onset (3–5 years) than typically expected for aging dogs (8–10 years). Studying this complex trait within pure breeds of dog may greatly increase our ability to identify genomic regions associated with risk of hearing impairment in dogs and in humans. We performed a genome-wide association study (GWAS) to detect loci underlying adult-onset deafness in a sample of 20 affected and 28 control Border Collies. We identified a region on canine chromosome 6 that demonstrates extended support for association surrounding SNP Chr6.25819273 (p-value = 1.09×10−13). To further localize disease-associated variants, targeted next-generation sequencing (NGS) of one affected and two unaffected dogs was performed. Through additional validation based on targeted genotyping of additional cases (n = 23 total) and controls (n = 101 total) and an independent replication cohort of 16 cases and 265 controls, we identified variants in USP31 that were strongly associated with adult-onset deafness in Border Collies, suggesting the involvement of the NF-κB pathway. We found additional support for involvement of RBBP6, which is critical for cochlear development. These findings highlight the utility of GWAS–guided fine-mapping of genetic loci using targeted NGS to study hereditary disorders of the domestic dog that may be analogous to human disorders. PMID:23028339

Marriage trends among Americans with childhood-onset disabilities, 1997-2013.

PubMed

Tumin, Dmitry

2016-10-01

People with disabilities are less likely to marry than people without disabilities. Trends in marriage and assortative mating among people with disabilities have not been investigated. This study tested if marriage likelihood converged between adults with childhood-onset disabilities and their peers, and if married adults with childhood-onset disabilities became more likely to have a spouse without disabilities. U.S. data from annual National Health Interview Surveys were used to identify adults ages 18-44 surveyed between 1997 and 2013 (N = 562,229). Childhood-onset disability was defined by self-report of physical conditions limiting the respondent's activities since age <18 years. Weighted multivariate logistic regressions were used to compare trends in ever marrying and current marriage to a spouse without reported disabilities between adults with childhood-onset disabilities and adults without childhood-onset disabilities. Across survey years, the decline in odds of having ever married was stronger among adults with childhood-onset disabilities (OR = 0.94; 95% CI: 0.93, 0.95; p < 0.001) than among adults without childhood-onset disabilities (OR = 0.96; 95% CI: 0.96, 0.96; p < 0.001), and divergence in these trends was statistically significant (p = 0.001). Employment and college attendance were positively correlated with marriage among people with childhood-onset disabilities. Among adults married at the time of the survey, those with childhood-onset disabilities were less likely to have a spouse without reported disabilities. The American retreat from marriage has been accelerated among adults with childhood-onset disabilities, with high rates of in-marriage to other people with disabilities persisting in this group. Copyright © 2016 Elsevier Inc. All rights reserved.

Risk factors for antipsychotic medication non-adherence behaviors and attitudes in adult-onset psychosis.

PubMed

Hui, Christy Lai Ming; Poon, Venessa Wing Yan; Ko, Wai Tung; Miao, Ho Yee; Chang, Wing Chung; Lee, Edwin Ho Ming; Chan, Sherry Kit Wa; Lin, Jingxia; Chen, Eric Yu Hai

2016-07-01

Research on antipsychotic medication non-adherence in first-episode psychosis patients tends to examine non-adherence behaviors and attitudes together. Nonetheless, attitudes do not always directly translate into behaviors. We examined the baseline predictors for antipsychotics non-adherence behaviors and attitudes separately in a first-episode psychosis cohort. We also included cognitive impairments as one of the predictor variables as this domain is rarely explored in adherence studies. Participants were 313 adult-onset psychosis patients recruited from the Jockey Club Early Psychosis project in Hong Kong. Demographic, premorbid, clinical, and cognitive characteristics were first assessed at baseline. Six months later, participants completed a 14-item Medication Compliance Questionnaire, which was a modified and Cantonese-translated version of the Medication Adherence Rating Scale that includes items pertaining to both adherence behaviors and attitudes. Rates of poor adherence behaviors and negative adherence attitudes were 17.6% and 27.8%, respectively. Determinants of poor adherence behavior included more severe positive symptoms, hospitalization at onset of illness, and poorer engagement in extended social network. As for negative adherence attitude, determinants included more severe general psychopathology, poorer insight, more psychic medication side-effects, and poorer performance on backward digit span test and WAIS-R information test. The risk factors for non-adherence behaviors and attitudes are different and they should all be taken into careful consideration while formulating appropriate intervention programs to tackle the adherence problem in adult onset psychosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Body weight status and onset of functional limitations in U.S. middle-aged and older adults.

PubMed

An, Ruopeng; Shi, Yuyan

2015-07-01

The sweeping obesity epidemic could further increase the incidence of functional limitations in the U.S. rapidly aging population. To examine the relationship between body weight status and onset of functional limitations in U.S. middle-aged and older adults. Study sample came from 1992 to 2010 waves of the Health and Retirement Study, a nationally representative longitudinal survey of community-dwelling middle-aged and older adults. Body mass index (BMI) was calculated from self-reported height/weight. Functional limitations were classified into physical mobility limitation (PM), large muscle function limitation (LMF), activities of daily living limitation (ADL), gross motor function limitation (GMF), and fine motor function limitation (FMF). Mixed-effect logistic regressions were performed to estimate the relationship between prior-wave body weight status and current-wave onset of functional limitations, adjusted for individual characteristics and survey design. Prior-wave body weight status prospectively predicted onset of functional limitation, and the relationship showed a U-shaped pattern. Compared with their normal weight counterparts, the odds ratios (ORs) in underweight (BMI < 18.5) and obese (BMI ≥ 30) adults were 1.30 (95% confidence interval, 1.05-1.62) and 2.31 (2.11-2.52) for PM, 1.20 (0.96-1.50) and 1.63 (1.49-1.79) for LMF, 2.02 (1.66-2.46) and 1.40 (1.28-1.54) for ADL, 1.96 (1.60-2.39) and 1.77 (1.62-1.93) for GMF, and 1.66 (1.37-2.02) and 1.34 (1.22-1.46) for FMF, respectively. For PM, LMF and GMF, the impact of obesity appeared more pronounced in women, whereas that of underweight more pronounced in men. Proper weight management during aging is crucial in preventing functional limitations in middle-aged and older adults. Copyright © 2015 Elsevier Inc. All rights reserved.

Vitamin D status and age of onset of demyelinating disease.

PubMed

Brenton, J Nicholas; Koenig, Scott; Goldman, Myla D

2014-11-01

To evaluate the prevalence of and associated factors impacting vitamin D insufficiency and deficiency in childhood versus adult-onset demyelinating disease. We conducted a retrospective, cross-sectional, chart-review, cohort study on geographically-similar pediatric, young adult, and adult patients with a diagnosis of demyelinating disease identified at the University of Virginia from 2008 to 2013. Group prevalence of vitamin D insufficiency and deficiency as well as relevant factors associated with vitamin D status was analyzed and compared. We identified 24 childhood-onset (CO), 33 young adult-onset (Y-AO), and 59 adult-onset (AO) cases. There was no difference in the prevalence of vitamin D insufficiency or deficiency between the cohorts. Non-Caucasian race and elevated body mass index were significantly associated with low vitamin D levels, regardless of age of onset. In regression models, race and obesity were independent predictors of vitamin D status. The prevalence of obesity was significantly higher in the childhood-onset cohort (CO=58.5%; Y-AO=31%; AO=34%; p=0.02). Our findings demonstrate no difference in the prevalence of vitamin D insufficiency/deficiency between childhood and adult-onset demyelinating disease, suggesting age at disease onset is irrelevant to vitamin D status in demyelinating disease. Both race and obesity are independent factors associated with vitamin D insufficiency/deficiency, regardless of age of disease onset. Obesity, independent of gender, is significantly higher in children compared to adult patients diagnosed with multiple sclerosis and may have a role in the development of childhood-onset demyelinating disease. Copyright © 2014 Elsevier B.V. All rights reserved.

Primary Hyperparathyroidism and Hyperthyroidism in a Patient with Myotonic Dystrophy: A Case Report and Review of the Literature

PubMed Central

Alaya, Wafa; Berriche, Olfa; Younes, Samia; Sfar, Mohamed Habib

2015-01-01

Various endocrine manifestations are commonly described in myotonic dystrophy (MD), including primary hypogonadism, diabetes mellitus, and thyroid and parathyroid dysfunction. We describe a 46-year-old woman with a family history of MD with her son. She was diagnosed with cardiac arrhythmia and required the implantation of a pacemaker. She was noted to have a bilateral cataract. She complained of muscle weakness, diffuse myalgia, and palpitation. The electromyography (EMG) showed myotonic discharges. Laboratory tests showed high serum calcium 2.83 mmol/L, serum phosphate 1.2 mmol/L, parathormone 362.5 pg/mL, thyroid stimulating hormone TSH 0.02 mIU/L (normal range: 0.34–5.6 mIU/L), FT4 21.17 ng/mL, and negative anti-thyroperoxidase antibodies. Cervical ultrasound revealed a multinodular goiter. The 99mTc-MIBI scintigraphy localized a lower right parathyroid adenoma. The clinical data, the family history of MD, EMG data, and endocrine disturbances were strongly suggestive of MD associated with hyperthyroidism and primary hyperparathyroidism. PMID:26175917

Pigmentation Phenotype, Photosensitivity, and Skin Neoplasms in Patients with Myotonic Dystrophy

PubMed Central

Gadalla, Shahinaz M.; Hilbert, James E.; Martens, William B.; Givens, Shannon; Moxley, Richard T.; Greene, Mark H.

2017-01-01

Background Recent studies have suggested a possible excess risk of skin neoplasms in patients with myotonic dystrophy (DM). Risk factors related to this observation have not been defined. Method We collected information regarding personal history of skin tumors, pigmentation phenotype, and skin reaction to sun exposure from 266 DM patients who were enrolled in the US NIH National Registry of Myotonic Dystrophy and Facioscapulohumeral Muscular Dystrophy Patients and Family Members. Results Seventy-seven subjects reported having skin tumors that were either benign (n=31), malignant (n=32), or both (n=14). Female gender (OR=2.27, 95%CI=1.02–5.05, p=0.04), older age (OR=1.10, 95%CI=1.05–1.16, p<0.001), and DM1 subtype (OR=3.42, 95%CI=1.27–9.26, p=0.02) were associated with a malignant skin tumor. The association between malignant skin tumors and known risk factors [light eye color (OR=1.62, 95%CI=0.78–3.39, p=0.20); light skin complexion (OR=1.31, 95% CI=0.63–2.73, p=0.48), moderate/extensive face freckles (OR=1.47, 95% CI=0.50–4.34, p=0.49)] were modest. Strong, but not statistically significant, associations were noted with sunburn reactions when exposed to sunlight (OR=4.28, 95%CI=0.91–19.95, p=0.06, and 2.19, 95%CI=0.67–7.09, p=0.19 for sunburns with and without blistering, respectively). Conclusions Although our study was limited by small sample size, the risk factors for malignant skin tumors in DM strongly resemble the general population. We recommend that DM patients adhere to sun exposure protective behavior. PMID:28317292

Hypothyroidism in late-onset Pompe disease.

PubMed

Schneider, Joseph; Burmeister, Lynn A; Rudser, Kyle; Whitley, Chester B; Jarnes Utz, Jeanine

2016-09-01

In Pompe disease, a deficiency of acid α-glucosidase enzyme activity leads to pathologic accumulation of glycogen in tissues. Phenotype heterogeneity in Pompe includes an infantile form and late-onset forms (juvenile- and adult-onset forms). Symptoms common to all phenotypes include progressive muscle weakness and worsening respiratory function. Patients with late-onset forms of Pompe disease commonly complain of chronic fatigue and generalized muscle weakness prior to being diagnosed with Pompe disease, and this may lead to consideration of hypothyroidism in the differential diagnosis. This study aimed to evaluate the prevalence of hypothyroidism in the adult-onset form of Pompe disease. Electronic chart review was performed at the Advanced Therapies Clinic at the University of Minnesota Medical Center (UMMC) to identify patients with late-onset Pompe disease. The identified charts were reviewed for a co-diagnosis of hypothyroidism. A query was made to the clinical data repository at UMMC searching diagnosis ICD9 code 244.9 (hypothyroidism not otherwise specified) and/or presence of levothyroxine from 2011 to 2014 in patients 18 years of age and older. The clinical data repository found a prevalence of hypothyroidism of 3.15% (56,072 of 1,782,720 patients) in the adult patient population at UMMC. Ten adult patients with Pompe disease were identified, five with the diagnosis of hypothyroidism (50%, 95% CI: 23.7, 76.3, p < 0.001 compared with the general UMMC adult population). Hypothyroidism was found at a higher prevalence in patients with late-onset Pompe disease compared to the general adult population at UMMC. Studies in larger populations of patients with Pompe disease would be needed to confirm an association of Pompe disease and hypothyroidism. Challenges include finding an adequate sample size, due the rarity of Pompe disease.

Depressive symptoms and the incidence of adult-onset asthma in African American women

PubMed Central

Coogan, Patricia F.; Yu, Jeffrey; O’Connor, George T.; Brown, Timothy A.; Palmer, Julie R.; Rosenberg, Lynn

2014-01-01

Background Some evidence suggests that depression may increase the risk of adult-onset asthma. No data are available for African American women, in whom the prevalence of depression and asthma is high. Objective To conduct prospective analyses of the relation of depressive symptoms to asthma incidence in the Black Women’s Health Study, a prospective cohort of US black women followed since 1995 with mailed biennial questionnaires. Methods Of 31,848 participants followed from 1999 to 2011, 771 reported incident asthma. Depressive symptoms were ascertained on 1999 and 2005 follow-up questionnaires with the Center for Epidemiological Studies–Depression Scale (CES-D). Participants rated the frequency of 20 symptoms. A score was calculated by summing the responses to all questions. Cox regression models were used to derive incidence rate ratios and 95% confidence intervals for 4 categories of the CES-D score in relation to incident asthma, adjusted for body mass index, smoking, and other covariates. Results The multivariable incidence rate ratio in the highest category of CES-D score (≥33) compared with the lowest (<16) was 2.08 (95% confidence interval 1.58–2.74), with a significant trend (P < .0001). The incidence rate ratio was higher in women who took antidepressants, were current or former smokers, were not obese, and were at least 40 years old, although there were no statistically significant interactions. Conclusion A positive association was observed between CES-D score and the incidence of adult-onset asthma. If the hypothesis is confirmed, depression could contribute substantially to the burden of asthma in adults. PMID:24440322

Late-adult onset Leigh syndrome.

PubMed

McKelvie, Penelope; Infeld, Bernard; Marotta, Rosetta; Chin, Judy; Thorburn, David; Collins, Steven

2012-02-01

We report an illustrative case of a 74-year-old man who, in the absence of intercurrent illness, presented with rapid cognitive decline. MRI showed bilateral, symmetrical, high T2-weighted signal in the anterior basal ganglia and medial thalami, extending to the periaqueductal grey matter, basal ganglia and basal frontal lobes. A (18)F-fluorodeoxyglucose-positron emission tomography scan showed widespread reduction of metabolism in the cortex of the frontal, temporal and parietal lobes, posterior cingulate gyrus, precuneus and caudate nuclei, with sparing of the sensorimotor cortex, thalami and lentiform nuclei. A mild vitamin B12 deficiency was found and despite normal thiamine levels, intravenous (IV) thiamine and vitamin B therapy was commenced, with a short course of IV methylprednisolone and tetracycline. Repeat neuropsychological assessment four weeks following treatment revealed increased alertness and interactiveness but significant cognitive decline persisted. Unexpectedly, the patient suffered a transmural anterior myocardial infarction six weeks after presentation and died within 24hours. An a autopsy showed: global reduction in cytochrome oxidase (COX) activity in all skeletal muscles examined; bilateral, symmetrical, hypervascular, focally necrotizing lesions in the substantia nigra, periaqueductal grey matter, superior colliculi, medial thalami anteriorly and posteriorly, as well as in the putamena but the mammillary bodies were not affected. Biochemical analysis of fresh muscle confirmed selective deficiency of complex IV of the oxidative phosphorylation chain. A diagnosis of late-adult onset Leigh syndrome was made. Multiple genetic studies failed to identify the specific underlying mutation. The relevant literature is reviewed. Copyright © 2011 Elsevier Ltd. All rights reserved.

Relation of Obesity to New-Onset Atrial Fibrillation and Atrial Flutter in Adults.

PubMed

Foy, Andrew J; Mandrola, John; Liu, Guodong; Naccarelli, Gerald V

2018-05-01

Prospective cohort studies involving older adults report an association of obesity and new-onset atrial fibrillation and atrial flutter. To assess this relation, we performed a longitudinal cohort study from January 1, 2006 to December 31, 2013, using a national claims database that tracks all inpatient, outpatient, and pharmacy claims data. The primary end point of new-onset atrial fibrillation was compared between obese and nonobese cohorts. We used logistic regression to determine the strength of association between obesity and new-onset atrial fibrillation controlling for age, gender, hypertension, and diabetes. Overall, 67,278 subjects were included in the cohort, divided evenly between those with and without a diagnosis of obesity. Obese subjects were significantly more likely to have hypertension (29.5% vs 14.6%) and diabetes (12.7% vs 5.2%) at study onset. Over 8 years of follow-up, we recorded a new diagnosis of atrial fibrillation in 1,511 (2.2%) subjects. Obesity was strongly associated with a new diagnosis of atrial fibrillation after controlling for age, gender, hypertension, and diabetes (odds ratio 1.4, 95% confidence interval 1.3 to 1.6). In conclusion, this information contributes to the growing evidence supporting the causal relation between obesity and atrial fibrillation, and emphasizes the need of addressing obesity as part of our therapeutic strategy to prevent atrial fibrillation. Copyright © 2018 Elsevier Inc. All rights reserved.

Leptin Signaling in AgRP Neurons Modulates Puberty Onset and Adult Fertility in Mice.

PubMed

Egan, Olivia K; Inglis, Megan A; Anderson, Greg M

2017-04-05

The hormone leptin indirectly communicates metabolic information to brain neurons that control reproduction, using GABAergic circuitry. Agouti-related peptide (AgRP) neurons in the arcuate nucleus are GABAergic, express leptin receptors (LepR), and are known to influence reproduction. This study tested whether leptin actions on AgRP neurons are required and sufficient for puberty onset and subsequent fertility. First, Agrp- Cre and Lepr- flox mice were used to target deletion of LepR to AgRP neurons. AgRP-LepR knock-out female mice exhibited mild obesity and adiposity as described previously, as well as a significant delay in the pubertal onset of estrous cycles compared with control animals. No significant differences in male puberty onset or adult fecundity in either sex were observed. Next, mice with a floxed polyadenylation signal causing premature transcriptional termination of the Lepr gene were crossed with AgRP-Cre mice to generate mice with AgRP neuron-specific rescue of LepR. Lepr-null control males and females were morbidly obese and exhibited delayed puberty onset, no evidence of estrous cycles, and minimal fecundity. Remarkably, AgRP-LepR rescue partially or fully restored all of these reproductive attributes to levels similar to those of LepR-intact controls despite minimal rescue of metabolic function. These results indicate that leptin signaling in AgRP neurons is sufficient for puberty onset and normal adult fecundity in both sexes when leptin signaling is absent in all other cells and that in females, the absence of AgRP neuron leptin signaling delays puberty. These actions appear to be independent of leptin's metabolic effects. SIGNIFICANCE STATEMENT Sexual maturation and fertility are dispensable at the individual level but critical for species survival. Conditions such as nutritional imbalance may therefore suppress puberty onset and fertility in an individual. In societies characterized by widespread obesity, the sensitivity of reproduction to

Neurobiology of Childhood-Onset Schizophrenia

ERIC Educational Resources Information Center

Biswas, Parthasarathy

2008-01-01

In the last decade there has been an exponential increase in studies on neurobiological measures in childhood-onset schizophrenia (COS). There seems to be a consensus that structural changes in COS are more marked than in adolescence-onset (AdOS) or adult-onset schizophrenia (AOS). Atrophy of total brain volume is progressive throughout the course…

Transgenerational epigenetic effects of the endocrine disruptor vinclozolin on pregnancies and female adult onset disease.

PubMed

Nilsson, Eric E; Anway, Matthew D; Stanfield, Jacob; Skinner, Michael K

2008-05-01

Endocrine disruptor exposure during gonadal sex determination was previously found to induce male rat adult onset transgenerational disease (F1-F4 generation), and this was associated with an alteration in the epigenetic (i.e., DNA methylation) programming of the male germ line. The current study was designed to characterize the transgenerational disease phenotypes of the female adult offspring. Pregnant rats (F0 generation) were treated transiently with vinclozolin (i.e., fungicide with anti-androgenic activity) on embryonic (E) days E8-E14 of gestation. F1 control and vinclozolin generation offspring from different litters were mated to produce F2 offspring, and similarly F2 generation animals produced F3 generation offspring. Observations demonstrated that 9 out of 105 pregnant rats (8.6%) from the vinclozolin F1-F3 generations exhibited uterine hemorrhage and/or anemia late in pregnancy. None (0 out of 82) of the control F1-F3 generation females had similar pregnancy problems. Complete blood cell counts and serum chemistry profiles demonstrated that selected vinclozolin generation animals, but not controls, exhibited marked regenerative anemia in late pregnancy. Examination of kidney histology revealed moderate or severe glomerular abnormalities in 67% of the vinclozolin F2 and F3 generation adult females compared with 18% of the controls. Adult female vinclozolin generation animals also developed various types of tumors in 6.5% of the animals (11 out of 170), while 2% of control-line animals (3 out of 151) developed mammary tumors. Observations demonstrate that vinclozolin exposure during gonadal sex determination promotes a transgenerational increase in pregnancy abnormalities and female adult onset disease states.

Transgenerational epigenetic effects of the endocrine disruptor vinclozolin on pregnancies and female adult onset disease

PubMed Central

Nilsson, Eric E; Anway, Matthew D; Stanfield, Jacob; Skinner, Michael K

2017-01-01

Endocrine disruptor exposure during gonadal sex determination was previously found to induce male rat adult onset transgenerational disease (F1–F4 generation), and this was associated with an alteration in the epigenetic (i.e., DNA methylation) programming of the male germ line. The current study was designed to characterize the transgenerational disease phenotypes of the female adult offspring. Pregnant rats (F0 generation) were treated transiently with vinclozolin (i.e., fungicide with anti-androgenic activity) on embryonic (E) days E8–E14 of gestation. F1 control and vinclozolin generation offspring from different litters were mated to produce F2 offspring, and similarly F2 generation animals produced F3 generation offspring. Observations demonstrated that 9 out of 105 pregnant rats (8.6%) from the vinclozolin F1–F3 generations exhibited uterine hemorrhage and/or anemia late in pregnancy. None (0 out of 82) of the control F1–F3 generation females had similar pregnancy problems. Complete blood cell counts and serum chemistry profiles demonstrated that selected vinclozolin generation animals, but not controls, exhibited marked regenerative anemia in late pregnancy. Examination of kidney histology revealed moderate or severe glomerular abnormalities in 67% of the vinclozolin F2 and F3 generation adult females compared with 18% of the controls. Adult female vinclozolin generation animals also developed various types of tumors in 6.5% of the animals (11 out of 170), while 2% of control-line animals (3 out of 151) developed mammary tumors. Observations demonstrate that vinclozolin exposure during gonadal sex determination promotes a transgenerational increase in pregnancy abnormalities and female adult onset disease states. PMID:18304984

The role of environmental factors for the onset of restricted mobility outside the home among older adults with osteoarthritis: a prospective cohort study.

PubMed

Rantakokko, Merja; Wilkie, Ross

2017-06-30

The study examines how environmental factors contribute to the onset of restricted mobility outside the home among older adults with osteoarthritis. This is a prospective cohort study of adults aged 50 years and older with osteoarthritis (n=1802). Logistic regression tested the association between the onset of restricted mobility outside the home and health, sociodemographic and perceived environmental barriers (hills and steep slopes, inaccessible public buildings, poor pavement condition, lack of access to public parks or sport facilities, heavy traffic or speeding cars and poor weather). The potential moderating role of environmental barriers on the association between health factors and onset was examined using interaction terms and stratified analysis. Of 1802 participants, 13.5% (n=243) reported the onset of restricted mobility outside the home at 3-year follow-up. Walking disability, anxiety, depression, cognitive impairment and obesity and all environmental barriers were associated with onset after adjustment for confounders. Environmental barriers had an added contribution to the effect of the health conditions on onset of restricted mobility, which was attenuated when adjusted for confounders. The added contribution remained only for walking disability and the presence of hills and steep slopes; in the presence of both, the association with onset of restricted mobility was stronger (OR 7.66, 95% CI 4.64 to 12.64) than in the presence of walking disability (3.60, 2.43 to 5.32) or the presence of hills and steep slopes alone (4.55, 2.89 to 7.16). For older adults with osteoarthritis, environmental barriers are associated and add a contribution to that of morbidities and walking disability on the onset of restricted mobility outside the home. Awareness of environmental barriers is important when aiming to maintain mobility and activities outside the home despite health conditions in older adults. © Article author(s) (or their employer(s) unless otherwise

Progressive Non-familial Adult onset Cerebellar Degeneration: An Unusual Occurrence with Hashimoto's Thyroiditis.

PubMed

Rao, Raghavendra S; Sheshadri, Shubha; Bhattacharjee, Dipanjan; Patil, Navin; Rao, Karthik

2018-03-13

Progressive non-familial adult onset cerebellar degeneration has been rarely associated with hypothyroidism and is known to be reversible after therapy. We report a case of cerebellar atrophy in a 31 year old female whose detailed evaluation had revealed sub-clinical hypothyroidism secondary to autoimmune thyroiditis with a very high anti-TPO (anti-thyroid peroxidase) antibody levels. MRI (Magnetic Resonanace Imaging) of brain showed diffuse bilateral cerebellar atrophy. She was treated with thyroid hormone supplementation and after one year of follow up, cerebellar signs had disappeared completely with significant reduction in anti-TPO antibody levels. Imaging of the brain post one year of follow-up revealed normal cerebellum. Hence, we opine that thyroid dysfunction should always be kept in mind while evaluating patients presenting with acute onset cerebellar ataxia as it can be easily reversed with thyroid hormone replacement therapy.

Prenatal Testing for Adult-Onset Conditions: the Position of the National Society of Genetic Counselors.

PubMed

Hercher, Laura; Uhlmann, Wendy R; Hoffman, Erin P; Gustafson, Shanna; Chen, Kelly M

2016-12-01

Advances in genetic testing and the availability of such testing in pregnancy allows prospective parents to test their future child for adult-onset conditions. This ability raises several complex ethical issues. Prospective parents have reproductive rights to obtain information about their fetus. This information may or may not alter pregnancy management. These rights can be in conflict with the rights of the future individual, who will be denied the right to elect or decline testing. This paper highlights the complexity of these issues, details discussions that went into the National Society of Genetic Counselors (NSGC) Public Policy Task Force's development of the Prenatal testing for Adult-Onset Conditions position statement adopted in November 2014, and cites relevant literature on this topic through December 2015. Issues addressed include parental rights and autonomy, rights of the future child, the right not to know, possible adverse effects on childhood and the need for genetic counseling. This paper will serve as a reference to genetic counselors and healthcare professionals when faced with this situation in clinical practice.

Analysis of meiotic segregation, using single-sperm typing: Meiotic drive at the myotonic dystrophy locus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leeflang, E.P.; Arnheim, N.; McPeek, M.S.

Meiotic drive at the myotonic dystrophy (DM) locus has recently been suggested as being responsible for maintaining the frequency, in the human population, of DM chromosomes capable of expansion to the disease state. In order to test this hypothesis, we have studied samples of single sperm from three individuals heterozygous at the DM locus, each with one allele larger and one allele smaller than 19 CTG repeats. To guard against the possible problem of differential PCR amplification rates based on the lengths of the alleles, the sperm were also typed at another closely linked marker whose allele size was unrelatedmore » to the allele size at the DM locus. Using statistical models specifically designed to study single-sperm segregation data, we find no evidence of meiotic segregation distortion. The upper limit of the two-sided 95% confidence interval for the estimate of the common segregation probability for the three donors is at or below .515 for all models considered, and no statistically significant difference from .5 is detected in any of the models. This suggests that any greater amount of segregation distortion at the myotonic dystrophy locus must result from events following sperm ejaculation. The mathematical models developed make it possible to study segregation distortion with high resolution by using sperm-typing data from any locus. 26 refs., 1 fig., 8 tabs.« less

Older adults in jail: high rates and early onset of geriatric conditions.

PubMed

Greene, Meredith; Ahalt, Cyrus; Stijacic-Cenzer, Irena; Metzger, Lia; Williams, Brie

2018-02-17

The number of older adults in the criminal justice system is rapidly increasing. While this population is thought to experience an early onset of aging-related health conditions ("accelerated aging"), studies have not directly compared rates of geriatric conditions in this population to those found in the general population. The aims of this study were to compare the burden of geriatric conditions among older adults in jail to rates found in an age-matched nationally representative sample of community dwelling older adults. This cross sectional study compared 238 older jail inmates age 55 or older to 6871 older adults in the national Health and Retirement Study (HRS). We used an age-adjusted analysis, accounting for the difference in age distributions between the two groups, to compare sociodemographics, chronic conditions, and geriatric conditions (functional, sensory, and mobility impairment). A second age-adjusted analysis compared those in jail to HRS participants in the lowest quintile of wealth. All geriatric conditions were significantly more common in jail-based participants than in HRS participants overall and HRS participants in the lowest quintile of net worth. Jail-based participants (average age of 59) experienced four out of six geriatric conditions at rates similar to those found in HRS participants age 75 or older. Geriatric conditions are prevalent in older adults in jail at significantly younger ages than non-incarcerated older adults suggesting that geriatric assessment and geriatric-focused care are needed for older adults cycling through jail in their 50s and that correctional clinicians require knowledge about geriatric assessment and care.

Transition of adolescent and young adult patients with childhood-onset chronic kidney disease from pediatric to adult renal services: a nationwide survey in Japan.

PubMed

Hattori, Motoshi; Iwano, Masayuki; Sako, Mayumi; Honda, Masataka; Okada, Hirokazu; Akioka, Yuko; Ashida, Akira; Kawasaki, Yukihiko; Kiyomoto, Hideyasu; Terada, Yoshio; Hirano, Daishi; Fujieda, Mikiya; Fujimoto, Shouichi; Masaki, Takao; Maruyama, Shoichi; Mastuo, Seiich

2016-12-01

Transition of adolescent and young adult (AYA) patients with childhood-onset chronic kidney diseases (C-CKD) from pediatric to adult renal services has received increasing attention. However, information on transition of Japanese patients with C-CKD is limited. The Transition Medicine Working Group, in collaboration with the Japanese Society for Nephrology, the Japanese Society for Pediatric Nephrology and the Japanese Society of Pediatric Urology, conducted a retrospective cross-sectional study in 2014 on issues concerning the transition of Japanese patients with C-CKD. Few institutions in Japan had transition programs and/or transition coordinators for patients with C-CKD. Refusal to transfer by patients or their families, lack of concern about transition and inability to decide on transfer were common reasons for non-transfer of patients still followed by pediatric renal services. Around 25 % of patients who had ended or interrupted follow-up by pediatric renal services presented to adult renal services because of symptoms associated with C-CKD. Patients with various types of childhood-onset nephrourological diseases were transferred from pediatric to adult renal services. IgA nephropathy, minimal change nephrotic syndrome and congenital anomalies of the kidney and urinary tract were the most frequent primary kidney diseases in adult patients with C-CKD. These survey results indicate the need for introduction of transitional care for Japanese AYA patients with C-CKD. Consensus guidelines for the optimal clinical management of AYA patients with C-CKD are required to ensure the continuity of care from child to adult renal services.

Statins and New-Onset Diabetes Mellitus and Diabetic Complications: A Retrospective Cohort Study of US Healthy Adults.

PubMed

Mansi, Ishak; Frei, Christopher R; Wang, Chen-Pin; Mortensen, Eric M

2015-11-01

Statin use is associated with increased incidence of diabetes and possibly with increased body weight and reduced exercise capacity. Data on the long-term effects of these associations in healthy adults, however, are very limited. In addition, the relationship between these effects and diabetic complications has not been adequately studied. To examine the association between statin use and new-onset diabetes, diabetic complications, and overweight/obesity in a cohort of healthy adults. This was a retrospective cohort study. Subjects were Tricare beneficiaries who were evaluated between October 1, 2003 and March 1, 2012. Patients were divided into statin users and nonusers. We excluded patients who, at baseline, had a preexisting disease indicative of cardiovascular diseases, any positive element of the Charlson comorbidity index (including diabetes mellitus), or life-limiting chronic diseases. Using 42 baseline characteristics, we generated a propensity score to match statin users and nonusers. Outcomes assessed included new-onset diabetes, diabetic complications, and overweight/obesity. A total of 25,970 patients (3982 statin users and 21,988 nonusers) were identified as healthy adults at baseline. Of these, 3351 statins users and 3351 nonusers were propensity score-matched. Statin users had higher odds of new-onset diabetes (odds ratio [OR] 1.87; 95 % confidence interval [95 % CI] 1.67-2.01), diabetes with complications (OR 2.50; 95 % CI 1.88-3.32), and overweight/obesity (OR 1.14; 95 % CI 1.04-1.25). Secondary and sensitivity analyses demonstrated similar findings. Diabetes, diabetic complications, and overweight/obesity were more commonly diagnosed among statin-users than similar nonusers in a healthy cohort of adults. This study demonstrates that short-term clinical trials might not fully describe the risk/benefit of long-term statin use for primary prevention.

Genes Interacting with Occupational Exposures to Low Molecular Weight Agents and Irritants on Adult-Onset Asthma in Three European Studies

PubMed Central

Rava, Marta; Ahmed, Ismail; Kogevinas, Manolis; Le Moual, Nicole; Bouzigon, Emmanuelle; Curjuric, Ivan; Dizier, Marie-Hélène; Dumas, Orianne; Gonzalez, Juan R.; Imboden, Medea; Mehta, Amar J.; Tubert-Bitter, Pascale; Zock, Jan-Paul; Jarvis, Deborah; Probst-Hensch, Nicole M.; Demenais, Florence; Nadif, Rachel

2016-01-01

Background: The biological mechanisms by which cleaning products and disinfectants—an emerging risk factor—affect respiratory health remain incompletely evaluated. Studying genes by environment interactions (G × E) may help identify new genes related to adult-onset asthma. Objectives: We identified interactions between genetic polymorphisms of a large set of genes involved in the response to oxidative stress and occupational exposures to low molecular weight (LMW) agents or irritants on adult-onset asthma. Methods: Our data came from three large European cohorts: Epidemiological Family-based Study of the Genetics and Environment of Asthma (EGEA), Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults (SAPALDIA), and European Community Respiratory Health Survey in Adults (ECRHS). A candidate pathway–based strategy identified 163 genes involved in the response to oxidative stress and potentially related to exposures to LMW agents/irritants. Occupational exposures were evaluated using an asthma job-exposure matrix and job-specific questionnaires for cleaners and healthcare workers. Logistic regression models were used to detect G × E interactions, adjusted for age, sex, and population ancestry, in 2,599 adults (mean age, 47 years; 60% women, 36% exposed, 18% asthmatics). p-Values were corrected for multiple comparisons. Results: Ever exposure to LMW agents/irritants was associated with current adult-onset asthma [OR = 1.28 (95% CI: 1.04, 1.58)]. Eight single nucleotide polymorphism (SNP) by exposure interactions at five loci were found at p < 0.005: PLA2G4A (rs932476, chromosome 1), near PLA2R1 (rs2667026, chromosome 2), near RELA (rs931127, rs7949980, chromosome 11), PRKD1 (rs1958980, rs11847351, rs1958987, chromosome 14), and PRKCA (rs6504453, chromosome 17). Results were consistent across the three studies and after accounting for smoking. Conclusions: Using a pathway-based selection process, we identified novel genes potentially involved

Enhanced Contribution of HLA in Pediatric Onset Ulcerative Colitis.

PubMed

Venkateswaran, Suresh; Prince, Jarod; Cutler, David J; Marigorta, Urko M; Okou, David T; Prahalad, Sampath; Mack, David; Boyle, Brendan; Walters, Thomas; Griffiths, Anne; Sauer, Cary G; LeLeiko, Neal; Keljo, David; Markowitz, James; Baker, Susan S; Rosh, Joel; Pfefferkorn, Marian; Heyman, Melvin B; Patel, Ashish; Otley, Anthony; Baldassano, Robert; Noe, Joshua; Rufo, Paul; Oliva-Hemker, Maria; Davis, Sonia; Zwick, Michael E; Gibson, Greg; Denson, Lee A; Hyams, Jeffrey; Kugathasan, Subra

2018-03-19

The genetic contributions to pediatric onset ulcerative colitis (UC), characterized by severe disease and extensive colonic involvement, are largely unknown. In adult onset UC, Genome Wide Association Study (GWAS) has identified numerous loci, most of which have a modest susceptibility risk (OR 0.84-1.14), with the exception of the human leukocyte antigen (HLA) region on Chromosome 6 (OR 3.59). To study the genetic contribution to exclusive pediatric onset UC, a GWAS was performed on 466 cases with 2099 healthy controls using UK Biobank array. SNP2HLA was used to impute classical HLA alleles and their corresponding amino acids, and the results are compared with adult onset UC. HLA explained the almost entire association signal, dominated with 191 single nucleotide polymorphisms (SNPs) (p = 5 x 10-8 to 5 x 10-10). Although very small effects, established SNPs in adult onset UC loci had similar direction and magnitude in pediatric onset UC. SNP2HLA imputation identified HLA-DRB1*0103 (odds ratio [OR] = 6.941, p = 1.92*10-13) as the most significant association for pediatric UC compared with adult onset UC (OR = 3.59). Further conditioning showed independent effects for HLA-DRB1*1301 (OR = 2.25, p = 7.92*10-9) and another SNP rs17188113 (OR = 0.48, p = 7.56*10-9). Two HLA-DRB1 causal alleles are shared with adult onset UC, while at least 2 signals are unique to pediatric UC. Subsequent stratified analyses indicated that HLA-DRB1*0103 has stronger association for extensive disease (E4: OR = 8.28, p = 4.66x10-10) and female gender (OR = 8.85, p = 4.82x10-13). In pediatric onset UC, the HLA explains almost the entire genetic associations. In addition, the HLA association is approximately twice as strong in pediatric UC compared with adults, due to a combination of novel and shared effects. We speculate the paramount importance of antigenic stimulation either by infectious or noninfectious stimuli as a causal event in pediatric UC onset.

Epigenetics of the myotonic dystrophy-associated DMPK gene neighborhood

PubMed Central

Buckley, Lauren; Lacey, Michelle; Ehrlich, Melanie

2016-01-01

Aim: Identify epigenetic marks in the vicinity of DMPK (linked to myotonic dystrophy, DM1) that help explain tissue-specific differences in its expression. Materials & methods: At DMPK and its flanking genes (DMWD, SIX5, BHMG1 and RSPH6A), we analyzed many epigenetic and transcription profiles from myoblasts, myotubes, skeletal muscle, heart and 30 nonmuscle samples. Results: In the DMPK gene neighborhood, muscle-associated DNA hypermethylation and hypomethylation, enhancer chromatin, and CTCF binding were seen. Myogenic DMPK hypermethylation correlated with high expression and decreased alternative promoter usage. Testis/sperm hypomethylation of BHMG1 and RSPH6A was associated with testis-specific expression. G-quadruplex (G4) motifs and sperm-specific hypomethylation were found near the DM1-linked CTG repeats within DMPK. Conclusion: Tissue-specific epigenetic features in DMPK and neighboring genes help regulate its expression. G4 motifs in DMPK DNA and RNA might contribute to DM1 pathology. PMID:26756355

A longitudinal analysis of early risk factors for adult-onset offending: What predicts a delayed criminal career?

PubMed

Zara, Georgia; Farrington, David P

2010-10-01

Late-onset offending, at the age of 21 or thereafter, is an underexplored dimension of the criminal career. Our aims were to explore which factors are precursors of late-onset offending, and the extent to which adult criminality can be predicted in childhood and adolescence. This is the first study that defines late-onset offending based on a combination of official records and self-reports. Longitudinal data from the Cambridge Study in Delinquent Development (CSDD) were used. Four hundred and three South London men, followed from ages 8-10 to ages 48-50, were divided into late-starters (LS, n = 51), early-starters (ES, n = 140) and non-offenders (NO, n = 212). LS men were more likely than NO men to have been neurotic, truants or in poor housing at ages 8-10. At ages 12-14, they tended to be neurotic, and at ages 16-18, they had high unemployment and spent time hanging about on the streets. Compared with ES, LS were nervous at ages 8-10, and at age 18 they were more likely to be sexual virgins. Overall, LS men were more similar to NO men before age 21, but more similar to ES men by age 32. Our hypotheses that late-onset offenders would be particularly characterised by neuroticism or nervousness, but that this would buffer rather than fully protect over the life course, were sustained. Intervention to increase the resilience of children and adolescents who are rated as high on neurotic characteristics may lessen the burden that these factors impose in adult life and reduce the risk of a deteriorating quality of life and late onset criminal careers. © 2010 John Wiley & Sons, Ltd.

Effects of Functional Electrical Stimulation Lower Extremity Training in Myotonic Dystrophy Type I: A Pilot Controlled Study.

PubMed

Cudia, Paola; Weis, Luca; Baba, Alfonc; Kiper, Pawel; Marcante, Andrea; Rossi, Simonetta; Angelini, Corrado; Piccione, Francesco

2016-11-01

Functional electrical stimulation (FES) is a new rehabilitative approach that combines electrical stimulation with a functional task. This pilot study evaluated the safety and effectiveness of FES lower extremity training in myotonic dystrophy type 1. This is a controlled pilot study that enrolled 20 patients with myotonic dystrophy type 1 over 2 years. Eight patients (age, 39-67 years) fulfilled the inclusion criteria. Four participants performed FES cycling training for 15 days (one daily session of 30 minutes for 5 days a week). A control group, matched for clinical and genetic variables, who had contraindications to electrical stimulation, performed 6 weeks of conventional resistance and aerobic training. The modified Medical Research Council Scale and functional assessments were performed before and after treatment. Cohen d effect size was used for statistical analysis. Functional electrical stimulation induced lower extremity training was well tolerated and resulted in a greater improvement of tibialis anterior muscle strength (d = 1,583), overall muscle strength (d = 1,723), and endurance (d = 0,626) than conventional training. Functional electrical stimulation might be considered a safe and valid tool to improve muscle function, also in muscles severely compromised in which no other restorative options are available. Confirmation of FES efficacy through further clinical trials is strongly advised.

Adult-onset hypophosphatemic osteomalacia associated with Sjogren syndrome

PubMed Central

Shen, Guohua; Zhang, Yuwei; Hu, Shuang; Liu, Bin; Kuang, Anren

2017-01-01

Abstract Rationale: Hypophosphatemic osteomalacia (HO) is a metabolic bone disease, exhibiting different etiologies such as genetic mutation, tumor induction, dysimmunity, or renal disease. Sjogren's syndrome (SS) is a connective tissue disorder commonly involving exocrine glands; however kidney involvement is also encountered, leading to abnormal phosphorus metabolism, even HO. Patient concerns: A 47-year-old female patient presented progressively worsening pain in the chest wall, back and bilateral lower extremities as well as muscle weakness was referred to our department. Diagnoses, interventions and outcomes: Due to the laboratory test results, radiographic findings and pathologic results, she was diagnosed with adult-onset HO associated with SS. She was then treated with alkalinization, steroids, neutral phosphate, calcium supplements together with activated vitamin D. So far, she recovered uneventfully with relieved pain and increased serum phosphorus level. Lessons: HO may be secondary to renal tubular acidosis of SS patients, and it might be a diagnostic challenge when the kidney involvement in SS is latent and precede the typical sicca symptoms. PMID:28353596

Effect of thyroxine on munc-18 and syntaxin-1 expression in dorsal hippocampus of adult-onset hypothyroid rats

PubMed Central

Zhu, Y.; Ning, D.; Wang, F.; Liu, C.; Xu, Y.; Jia, X.; Zhu, D.

2012-01-01

Adult-onset hypothyroidism induces a variety of impairments on hippocampus- dependent neurocognitive functioningin which many synaptic proteins in hippocampus neurons are involved. Here, we observed the effect of adult-onset hypothyroidism on the expression of syntaxin-1 and munc-18 in the dorsal hippocampus and whether the altered proteins could be restored by levothyroxine (T4) treatment. All rats were separated into 4 groups randomly: hypothyroid group, 5 µg T4 /100 g body weight (BW) treated group, 20 µg T4/100 g BW treated group and control group. The radioimmunoassay kits were applied to assay the levels of serum T3 and T4, and the levels of syntaxin-1 and munc-18 in hippocampus were assessed by immunohistochemistry and Western blot. Both analysis corroborated that syntaxin-1 in the hypothyroid group was significantly higher. Munc-18 was lower in four layers of CA3 and dentate gyrus by immunohistochemistry. After two weeks of treatment with 5 µg T4/100 g BW for hypothyroidism, syntaxin-1 levels were completely restored, whereas the recovery of munc-18 only located in two of the four impaired layers. Twenty µg T4/100 g BW treatment normalized munc-18 levels. These data suggested that adult-onset hypothyroidism induced increment of syntaxin-1 and decrement of munc-18 in the dorsal hippocampus, which could be restored by T4 treatment. Larger dosage of T4 caused more effective restorations. PMID:22688303

[Therapy of adult-onset laryngeal papilloma: integrallty submucosal dissection of the tumor by CO2 laser].

PubMed

Lei, W B; Liu, Q H; Chai, L P; Zhu, X L; Wang, Z F; Li, Q M; Tang, H C; Jiang, A Y; Wen, Y H; Wen, W P

2016-10-07

Objective: To evaluate the feasibility and efficacy of the integrallty submucosal resection of adult-onset laryngeal papilloma by CO 2 laser. Methods: A group of 64 cases (36 males and 28 females, multipe lesions 54 cases and single lesion 10 cases, aged 18-75 years, mean age 43.13 years) with adult-onset laryngeal papilloma encountered in the first affliated hospital of Sun Yatsen university from 2009 to 2015 was retrospectively analyzed. All cases were treated with integrallty submucosal dissection of the tumor by CO 2 laser, and observed the changes of tumor integral scope, inter-operative, operative processes, postoperative voice quality, postoperative scarring, and the tracheotomy conditions, which were analysed and evaluated. Results: A total of 64 patients were followed up from 1 year to 5 years. Preoperative tumor integral scope of these patients averaged of 7.00. A total of 62 cases kept 0 score of the tumor integral scope for at least one year, which lead to a clinical cure rate of 96.9%. The inter-operative averaged of 25.7 months. The total operative processes of these patients were 87 times (mean time 1.36). Four cases resulted in postoperative scarring. However these was a good result in postoperative voice quality with a mean score 4.25. As to the changes of tumor integral scope, all cases got a declining score (mean score 6.72), which resulted in a remission rate of 100%. Conclusion: The integrallty submucosal dissection of adult-onset 1aryngeal papilloma by CO 2 laser was an effective way to reduce the tumor integral scope; lengthen their inter-operative; decrease the operative processes, avoid the occurrence of tracheotomy; and improve the postoperative voice quality. Most of the patients could even be cured ultimately.

Opioid-free general anesthesia in patient with Steinert syndrome (myotonic dystrophy)

PubMed Central

Gaszynski, Tomasz

2016-01-01

Abstract Introduction: We report on the anesthetic management using opioid-free method of a patient with Steinert syndrome (myotonic dystrophy, MD), autosomal dominant dystrophy which is characterized by consistent contracture of muscle following stimulation. A myotonic crisis can be induced by numerous factors including hypothermia, shivering, and mechanical or electrical stimulation. In patients with MD, hypersensitivity to anesthetic drugs, especially muscle relaxants and opioids, may complicate postoperative management. If opioids are employed (systemic or neuraxial), then ICU care and continuous pulse oximetry must be considered given the high risk for respiratory depression and aspiration. Patients with MD present high sensitivity to the usual anesthetics such as volatile and muscle relaxants (both depolarizing and nondepolarizing). Opioids may induce muscle rigidity in this type of MD. Therefore, omitting opioids is recommended. Due to hypersensitivity to opioids and increased susceptibility to intra- and postoperative complications, it is recommended to introduce opioid-free anesthesia (OFA), for example, with use of dexmedetomidine (DEX). This is a new method of conducting general anesthesia without opioids and is based on concept of multimodal approach to pain management. Methods: A 31-year-old male patient (183 cm, 69 kg) was scheduled for laparoscopic operation of cholecystectomy. The patient received intravenously (IV): propofol in a dose of 250 mg followed by continuous infusion, rocuronium in a dose of 20 mg, and DEX in a loading dose of 0.6 μg/kg over 10 minutes followed by continuous infusion of dose of 0.2 μg/kg/hour. Results: The course of anesthesia and postoperative period were uneventful. The patient exited the operating theatre in a good medical state, with vitals within normal limits and fully regained consciousness. Conclusion: DEX is effective and safe for moderately painful procedures in patients with the elevated risk of

Educational and vocational outcomes of adults with childhood- and adult-onset systemic lupus erythematosus: 9 years of follow-up

PubMed Central

Lawson, Erica F.; Hersh, Aimee O.; Trupin, Laura; von Scheven, Emily; Okumura, Megumi J.; Yazdany, Jinoos; Yelin, Edward H.

2014-01-01

Objective To compare educational and vocational outcomes among adults with childhood-onset SLE (cSLE) and adult-onset SLE (aSLE). Methods Data derive from the 2002–2010 cycles of the Lupus Outcomes Study, a longitudinal cohort of 1204 adult subjects with SLE. Subjects age 18–60 living in the U.S. (N=929) were included in the analysis, and were classified as cSLE if age at diagnosis was <18 years (N=115). Logistic regression was used to assess the unadjusted and adjusted effect of cSLE, gender, race/ethnicity, baseline age, urban or rural location and U.S. region on the likelihood of completing a bachelor’s degree. Generalized estimating equations were used to assess the effect of cSLE, demographics, education, and disease-related factors on the odds of employment, accounting for multiple observations over the study period. Results Subjects with cSLE were on average younger (29±10 versus 44±9 years), with longer disease duration (15±10 versus 11±8 years). Subjects with aSLE and cSLE subjects were equally likely to complete a bachelor’s degree. However, subjects with cSLE were significantly less likely to be employed, independent of demographic and disease characteristics (OR 0.62, 95% CI 0.42–0.91). Conclusion While subjects with SLE are just as likely as those with aSLE to complete college education, cSLE significantly increases the risk of not working in adulthood, even when controlling for disease and demographic factors. Exploring reasons for low rates of employment and providing vocational support may be important to maximize long-term functional outcomes in patients with cSLE. PMID:24877200

Differences in autoantibody profiles and disease activity and damage scores between childhood- and adult-onset systemic lupus erythematosus: a meta-analysis.

PubMed

Livingston, Brieanna; Bonner, Ashley; Pope, Janet

2012-12-01

Age at systemic lupus erythematosus (SLE) onset may impact autoantibodies, disease activity, and damage. A meta-analysis of all studies that directly compared childhood-onset lupus (cSLE) to adult-onset lupus was performed to determine which autoantibodies and whether activity and damage scores vary between adult- and pediatric-onset SLE. A literature search of the MEDLINE/PubMed, EMBASE, CINAHL, and SCOPUS databases (until January 2011) was conducted to identify relevant articles. Study quality was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology checklist. Two independent reviewers determined eligibility criteria. Pooled odds ratios and mean differences were calculated assuming random effects, and heterogeneity was estimated and presented as (odds ratios; 95% confidence interval). Of the 484 studies identified, 19 were eligible. The total number of patients was 7519. Mean trial quality was 18/32, ranging from 8 to 29. Several statistically significant differences were found: more frequently positive anti-dsDNA antibody (1.97; 1.31 to 2.96) and IgG/IgM anticardiolipin antibody (1.66; 1.20 to 2.28), and mean disease activity scores (SLE Disease Activity Index) (4.73; 2.13 to 7.32) were higher in cSLE. Disease damage [SLE damage index (SDI)] was lower in cSLE, but not significantly (0.50; -0.13 to 1.14). Rheumatoid factor was increased in adults (0.53; 0.32 to 0.87). The frequency of the autoantibodies and laboratories was not different between the groups (ANA, anti-Smith, anti-RNP, anti-U1RNP, anti-Ro and anti-La, antiphospholipid, lupus anticoagulant, complements, ssDNA, and Coomb's test). The results of this meta-analysis suggest that cSLE may have different autoantibody profiles (increased anti-dsDNA and anticardiolipin antibody, less rheumatoid factor), and more disease activity than adult-onset SLE. Damage may be less in children, but larger studies are needed. Copyright © 2012 Elsevier Inc. All rights reserved.

Autoantibodies to N-terminally truncated GAD improve clinical phenotyping of individuals with adult-onset diabetes: Action LADA 12.

PubMed

Achenbach, Peter; Hawa, Mohammed I; Krause, Stephanie; Lampasona, Vito; Jerram, Samuel T; Williams, Alistair J K; Bonifacio, Ezio; Ziegler, Anette G; Leslie, R David

2018-07-01

Adult-onset type 1 diabetes, in which the 65 kDa isoform of GAD (GAD65) is a major autoantigen, has a broad clinical phenotype encompassing variable need for insulin therapy. This study aimed to evaluate whether autoantibodies against N-terminally truncated GAD65 more closely defined a type 1 diabetes phenotype associated with insulin therapy. Of 1114 participants with adult-onset diabetes from the Action LADA (latent autoimmune diabetes in adults) study with sufficient sera, we selected those designated type 1 (n = 511) or type 2 diabetes (n = 603) and retested the samples in radiobinding assays for human full-length GAD65 autoantibodies (f-GADA) and N-terminally truncated (amino acids 96-585) GAD65 autoantibodies (t-GADA). Individuals' clinical phenotypes were analysed according to antibody binding patterns. Overall, 478 individuals were f-GADA-positive, 431 were t-GADA-positive and 628 were negative in both assays. Risk of insulin treatment was augmented in t-GADA-positive individuals (OR 4.69 [95% CI 3.57, 6.17]) compared with f-GADA-positive individuals (OR 3.86 [95% CI 2.95, 5.06]), irrespective of diabetes duration. Of 55 individuals who were f-GADA-positive but t-GADA-negative, i.e. with antibody binding restricted to the N-terminus of GAD65, the phenotype was similar to type 2 diabetes with low risk of progression to insulin treatment. Compared with these individuals with N-terminal GAD65-restricted GADA, t-GADA-positive individuals were younger at diagnosis (p = 0.005), leaner (p < 0.0001) and more often had multiple diabetes-associated autoantibodies (28.3% vs 7.3%; p = 0.0005). In individuals with adult-onset diabetes, presence of N-terminally truncated GAD65 autoantibodies is associated with the clinical phenotype of autoimmune type 1 diabetes and predicts insulin therapy.

Oropharyngeal dysphagia in myotonic dystrophy type 1: a systematic review.

PubMed

Pilz, Walmari; Baijens, Laura W J; Kremer, Bernd

2014-06-01

A systematic review was conducted to investigate the pathophysiology of and diagnostic procedures for oropharyngeal dysphagia in myotonic dystrophy (MD). The electronic databases Embase, PubMed, and The Cochrane Library were used. The search was limited to English, Dutch, French, German, Spanish, and Portuguese publications. Sixteen studies met the inclusion criteria. Two independent reviewers assessed the methodological quality of the included articles. Swallowing assessment tools, the corresponding protocols, the studies' outcome measurements, and main findings are summarized and presented. The body of literature on pathophysiology of swallowing in dysphagic patients with MD type 1 remains scant. The included studies are heterogeneous with respect to design and outcome measures and hence are not directly comparable. More importantly, most studies had methodological problems. These are discussed in detail and recommendations for further research on diagnostic examinations for swallowing disorders in patients with MD type 1 are provided.

Environmental Tobacco Smoke and Adult-Onset Asthma: A Population-Based Incident Case–Control Study

PubMed Central

Jaakkola, Maritta S.; Piipari, Ritva; Jaakkola, Niina; Jaakkola, Jouni J. K.

2003-01-01

Objectives. The authors assessed the effects of environmental tobacco smoke (ETS) on the development of asthma in adults. Methods. In the Pirkanmaa district of South Finland, all 21- to 63-year-old adults with new cases of asthma diagnosed during a 2.5-year period (n = 521 case patients, out of 441 000 inhabitants) and a random sample of control subjects from the source population (932 control subjects) participated in a population-based incident case–control study. Results. Risk of asthma was related to workplace ETS exposure (adjusted odds ratio [OR] = 2.16; 95% confidence interval [CI] = 1.26, 3.72) and home exposure (OR = 4.77; 95% CI = 1.29, 17.7) in the past year. Cumulative ETS exposure over a lifetime at work and at home increased the risk. Conclusions. This study indicates for the first time that both cumulative lifetime and recent ETS exposures increase the risk of adult-onset asthma. PMID:14652334

Delayed Onset Muscle Soreness After Inspiratory Threshold Loading in Healthy Adults

PubMed Central

Mathur, Sunita; Sheel, A. William; Road, Jeremy D.; Reid, W. Darlene

2010-01-01

Purpose: Skeletal muscle damage occurs following high-intensity or unaccustomed exercise; however, it is difficult to monitor damage to the respiratory muscles, particularly in humans. The aim of this study was to use clinical measures to investigate the presence of skeletal muscle damage in the inspiratory muscles. Methods: Ten healthy subjects underwent 60 minutes of voluntary inspiratory threshold loading (ITL) at 70% of maximal inspiratory pressure. Maximal inspiratory and expiratory mouth pressures, delayed onset muscle soreness on a visual analogue scale and plasma creatine kinase were measured prior to ITL, and at repeated time points after ITL (4, 24 and 48 hours post-ITL). Results: Delayed onset muscle soreness was present in all subjects 24 hours following ITL (intensity = 22 ± 6 mm; significantly higher than baseline p = 0.02). Muscle soreness was reported primarily in the anterior neck region, and was correlated to the amount of work done by the inspiratory muscles during ITL (r = 0.72, p = 0.02). However, no significant change was observed in maximal inspiratory or expiratory pressures or creatine kinase. Conclusions: These findings suggest that an intense bout of ITL results in muscle soreness primarily in the accessory muscles of inspiration, however, may be insufficient to cause significant muscle damage in healthy adults. PMID:20467514

Molecular genetic analysis for periodic fever syndromes: a supplemental role for the diagnosis of adult-onset Still's disease.

PubMed

Li, Hongbin; Abramova, Irina; Chesoni, Sandra; Yao, Qingping

2018-06-17

Adult-onset Still's disease (AOSD) represents a systemic autoinflammatory disease (SAID), and its diagnostic criteria are clinical without genetic testing. Given shared manifestations between AOSD and hereditary SAIDs, molecular analysis may help differentiate these diseases. A PubMed literature search was conducted using key words "adult-onset Still's disease," "autoinflammatory disease," and "genetic mutation" between 1970 and February 2018. Articles on genetic mutations in the genes MEFV, TNFRSF1A, mevalonate kinase, or NOD2 for hereditary SAIDs in AOSD/systemic onset juvenile idiopathic arthritis (SJIA) patients were reviewed and analyzed. Five case series studies consisting of a total of 162 of both adult and pediatric patients were included. All patients fulfilled the Yamaguchi criteria for AOSD or the diagnostic criteria for SJIA. The results showed that 31.4% (51/162) of patients were identified to carry at least one genetic variant for periodic fever syndromes. In addition, four patients with the diagnosis of SJIA in other reports were confirmed to have FMF or TRAPS with molecular testing. These data together suggest that some patients who satisfy the clinical diagnostic criteria for AOSD/SOJIA could well be diagnosed with other SAIDs; genetic testing, particularly for those with atypical presentation can be supplementary to the accurate disease diagnosis by excluding other autoinflammatory diseases. AOSD is a diagnosis of exclusion and shares common manifestations with other SAIDs. The currently employed clinical criteria for AOSD can cause misdiagnosis. An updated set of classification criteria to integrate the molecular genetic analysis to exclude other autoinflammatory diseases is warranted.

Predictive Medicine: Recombinant DNA Technology and Adult-Onset Genetic Disorders

PubMed Central

Hayden, Michael

1988-01-01

Genetic factors are of great importance in common adult-onset disorders such as atherosclerosis, cancer, and neuro-degenerative diseases. Advances in DNA technology now allow identification of persons at high-risk of developing some of these diseases. This advance is leading to predictive medicine. In some genetic disorders, such as those leading to atherosclerosis and cancer, identification of high-risk individuals allows intervention which alters the natural history of the disorder. In other diseases, for which there is no treatment, such as Huntington's disease, the application of this technology provides information that relieves uncertainty and may affect quality of life, but does not alter the course of the illness. General implementation of predictive testing programs awaits the results of pilot projects, which will demonstrate the needs, appropriate levels of support, and guidelines for delivery of such testing. PMID:21253100

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

PubMed

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

2012-10-01

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

A case of chronic active Epstein-Barr virus infection mimicking adult-onset Still's disease.

PubMed

Yoshioka, Katsunobu; Fukushima, Hiroko; Ishii, Naomi; Kita, Akiko; Hanioka, Yusuke; Minami, Mieko; Inoue, Takeshi; Yamagami, Keiko

2013-01-01

An 83-year-old man was diagnosed with adult-onset Still's disease (AOSD) based on clinical and laboratory findings. However, glucocorticoid had little effect. Epstein-Barr virus (EBV)-DNA was detected in peripheral blood, and autopsy findings confirmed a diagnosis of chronic active EBV infection (CAEBV). CAEBV mimics AOSD, and the presence of articular involvement and leukocytosis does not exclude the possibility of CAEBV. CAEBV should be included in the differential diagnosis of AOSD, and measurement of EBV-DNA is essential.

Development of a Genomic DNA Reference Material Panel for Myotonic Dystrophy Type 1 (DM1) Genetic Testing

PubMed Central

Kalman, Lisa; Tarleton, Jack; Hitch, Monica; Hegde, Madhuri; Hjelm, Nick; Berry-Kravis, Elizabeth; Zhou, Lili; Hilbert, James E.; Luebbe, Elizabeth A.; Moxley, Richard T.; Toji, Lorraine

2014-01-01

Myotonic dystrophy type 1 (DM1) is caused by expansion of a CTG triplet repeat in the 3′ untranslated region of the DMPK gene that encodes a serine-threonine kinase. Patients with larger repeats tend to have a more severe phenotype. Clinical laboratories require reference and quality control materials for DM1 diagnostic and carrier genetic testing. Well-characterized reference materials are not available. To address this need, the Centers for Disease Control and Prevention-based Genetic Testing Reference Material Coordination Program, in collaboration with members of the genetic testing community, the National Registry of Myotonic Dystrophy and Facioscapulohumeral Muscular Dystrophy Patients and Family Members, and the Coriell Cell Repositories, has established and characterized cell lines from patients with DM1 to create a reference material panel. The CTG repeats in genomic DNA samples from 10 DM1 cell lines were characterized in three clinical genetic testing laboratories using PCR and Southern blot analysis. DMPK alleles in the samples cover four of five DM1 clinical categories: normal (5 to 34 repeats), mild (50 to 100 repeats), classical (101 to 1000 repeats), and congenital (>1000 repeats). We did not identify or establish Coriell cell lines in the premutation range (35 to 49 repeats). These samples are publicly available for quality control, proficiency testing, test development, and research and should help improve the accuracy of DM1 testing. PMID:23680132

Juvenile-onset myasthenia gravis: autoantibody status, clinical characteristics and genetic polymorphisms.

PubMed

Hong, Yu; Skeie, Geir Olve; Zisimopoulou, Paraskevi; Karagiorgou, Katerina; Tzartos, Socrates J; Gao, Xiang; Yue, Yao-Xian; Romi, Fredrik; Zhang, Xu; Li, Hai-Feng; Gilhus, Nils Erik

2017-05-01

Myasthenia gravis (MG) is an autoimmune disorder mediated by antibodies against proteins at the neuromuscular junction. Juvenile-onset MG (JMG) has been reported to have special characteristics. It is still unclear whether there are any pathogenic and genetic differences between juvenile and adult MG. In this study, we evaluated the clinical characteristics, autoantibody status (antibodies against AChR, MuSK, LRP4, titin and RyR) and genetic susceptibility (CHRNA1, CTLA4 and AIRE) in 114 Chinese JMG patients, and compared with 207 young adult MG patients (onset age 18-40 years). JMG patients were classified into two subgroups: the very early onset group (<8 years) and puberty onset group (8-18 years). The very early onset MG patients had a higher proportion of ocular MG and thymus hyperplasia, compared with puberty onset MG and young adult MG (P < 0.05). AChR antibodies were found in majority of JMG patients and were associated with more severe disease (P < 0.05), while other antibodies were rare in JMG. Moreover, the very early onset MG had a more prominent genetic predisposition than puberty and adult MG, affecting the susceptible genes CHRNA1 and CTLA4. JMG has the same pathogenic background as adult MG, but has typical clinical features and a prominent genetic predisposition in very early onset patients (<8 years). Specific therapeutic considerations are needed.

Intravitreal dexamethasone implants for the treatment of refractory scleritis combined with uveitis in adult-onset Still's disease: a case report.

PubMed

Ahn, Seong Joon; Hwang, Sun Jin; Lee, Byung Ro

2016-11-08

Adult-onset Still's disease is a systemic inflammatory disease which presents with uveitis and scleritis in the eye. Intravitreal dexamethasone implants are used for the treatment of refractory uveitis. A 19-year-old woman diagnosed to have adult-onset Still's disease for fevers, joint pain, and a salmon-colored bumpy rash presented with scleritis and uveitis in the left eye. Topical and systemic steroids with oral methotrexate failed to control the inflammation. We performed intravitreal injections of dexamethasone implants for side effects of steroid and refractory ocular inflammation. The therapy resulted in improvements in the patient's uveitis with reductions in scleral vessel engorgement and redness. There was no recurrence of uveitis or scleritis during 4 months following treatment. Intravitreal injections of dexamethasone implants may result in clinical improvements of refractory scleritis combined with uveitis.

Inhaled corticosteroids and asthma control in adult-onset asthma: 12-year follow-up study.

PubMed

Vähätalo, Iida; Ilmarinen, Pinja; Tuomisto, Leena E; Niemelä, Onni; Kankaanranta, Hannu

2018-04-01

Prescribed inhaled corticosteroid (ICS) doses in asthma have been studied in cross-sectional settings whereas long-term follow-up studies have not been carried out. To evaluate prescribed medication longitudinally by calculating cumulative ICS doses and dose changes in a cohort of new-onset adult asthma during 12 years and in different groups of asthma control. A total of 203 patients were followed for 12 years as part of Seinäjoki Adult Asthma Study (SAAS). All asthma-related visits and prescribed medication over the study period were collected from medical records. Total cumulative ICS dose for the 12-year follow-up period was 3.4g (±SEM 0.1) per patient. Both respiratory specialists and GPs prescribed step-ups and step-downs in ICS treatment and in total 649 dose changes were noted during the follow-up (median 3(1-5) per patient). Patients with uncontrolled asthma received higher ICS doses throughout the follow-up period, and therefore, cumulative 12-year ICS dose (3.8g ± SEM 0.2) in this group was higher than that in those with partially controlled (3.4g ± SEM 0.2) or controlled disease (2.9g ± SEM 0.2) (p = 0.0001). Patients with uncontrolled asthma were also prescribed a higher number of ICS dose changes than patients with controlled disease. Despite frequent dose changes and high ICS doses during the 12-year follow-up, the level of asthma control remained poor in patients with uncontrolled asthma. This suggests that high ICS doses may not be effective enough for management of disease in patients with uncontrolled adult-onset asthma and novel targeted treatments are required. Copyright © 2018 Elsevier Ltd. All rights reserved.

Sensorimotor Oscillations Prior to Speech Onset Reflect Altered Motor Networks in Adults Who Stutter

PubMed Central

Mersov, Anna-Maria; Jobst, Cecilia; Cheyne, Douglas O.; De Nil, Luc

2016-01-01

Adults who stutter (AWS) have demonstrated atypical coordination of motor and sensory regions during speech production. Yet little is known of the speech-motor network in AWS in the brief time window preceding audible speech onset. The purpose of the current study was to characterize neural oscillations in the speech-motor network during preparation for and execution of overt speech production in AWS using magnetoencephalography (MEG). Twelve AWS and 12 age-matched controls were presented with 220 words, each word embedded in a carrier phrase. Controls were presented with the same word list as their matched AWS participant. Neural oscillatory activity was localized using minimum-variance beamforming during two time periods of interest: speech preparation (prior to speech onset) and speech execution (following speech onset). Compared to controls, AWS showed stronger beta (15–25 Hz) suppression in the speech preparation stage, followed by stronger beta synchronization in the bilateral mouth motor cortex. AWS also recruited the right mouth motor cortex significantly earlier in the speech preparation stage compared to controls. Exaggerated motor preparation is discussed in the context of reduced coordination in the speech-motor network of AWS. It is further proposed that exaggerated beta synchronization may reflect a more strongly inhibited motor system that requires a stronger beta suppression to disengage prior to speech initiation. These novel findings highlight critical differences in the speech-motor network of AWS that occur prior to speech onset and emphasize the need to investigate further the speech-motor assembly in the stuttering population. PMID:27642279

Effects of Aging and Adult-Onset Hearing Loss on Cortical Auditory Regions

PubMed Central

Cardin, Velia

2016-01-01

Hearing loss is a common feature in human aging. It has been argued that dysfunctions in central processing are important contributing factors to hearing loss during older age. Aging also has well documented consequences for neural structure and function, but it is not clear how these effects interact with those that arise as a consequence of hearing loss. This paper reviews the effects of aging and adult-onset hearing loss in the structure and function of cortical auditory regions. The evidence reviewed suggests that aging and hearing loss result in atrophy of cortical auditory regions and stronger engagement of networks involved in the detection of salient events, adaptive control and re-allocation of attention. These cortical mechanisms are engaged during listening in effortful conditions in normal hearing individuals. Therefore, as a consequence of aging and hearing loss, all listening becomes effortful and cognitive load is constantly high, reducing the amount of available cognitive resources. This constant effortful listening and reduced cognitive spare capacity could be what accelerates cognitive decline in older adults with hearing loss. PMID:27242405

Assessing the Dim Light Melatonin Onset in Adults with Autism Spectrum Disorder and No Comorbid Intellectual Disability.

PubMed

Baker, Emma K; Richdale, Amanda L; Hazi, Agnes; Prendergast, Luke A

2017-07-01

This study assessed melatonin levels and the dim light melatonin onset (DLMO) in adults with Autism Spectrum Disorder (ASD) and also investigated the relationships between melatonin and objectively measured sleep parameters. Sixteen adults with ASD (ASD-Only), 12 adults with ASD medicated for comorbid diagnoses of anxiety and/or depression (ASD-Med) and 32 controls participated in the study. Although, the timing of the DLMO did not differ between the two groups, advances and delays of the melatonin rhythm were observed in individual profiles. Overall mean melatonin levels were lower in the ASD-Med group compared to the two other groups. Lastly, greater increases in melatonin in the hour prior to sleep were associated with greater sleep efficiency in the ASD groups.

Sexual orientation versus age of onset as bases for typologies (subtypes) for gender identity disorder in adolescents and adults.

PubMed

Lawrence, Anne A

2010-04-01

The most widely used and influential typologies for transsexualism and gender identity disorder (GID) in adolescents and adults employ either sexual orientation or age of onset of GID-related symptoms as bases for categorization. This review compares these two typological approaches, with the goal of determining which one should be employed for the diagnosis of GID in Adolescents or Adults (or its successor diagnosis) in the forthcoming revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM). Typologies based on sexual orientation and age of onset of GID-related symptoms are roughly comparable in ease and reliability of subtype assignment. Typologies based on sexual orientation, however, employ subtypes that are less ambiguous and better suited to objective confirmation and that offer more concise, comprehensive clinical description. Typologies based on sexual orientation are also superior in their ability to predict treatment-related outcomes and comorbid psychopathology and to facilitate research. Commonly expressed objections to typologies based on sexual orientation are unpersuasive when examined closely. The DSM should continue to employ subtypes based on sexual orientation for the diagnosis of GID in Adolescents or Adults or its successor diagnosis.

Are early-onset cannabis smokers at an increased risk of depression spells?

PubMed

Fairman, Brian J; Anthony, James C

2012-04-01

A recent research focus is a set of hypothesized adult-onset mental health disturbances possibly due to early-onset cannabis use (EOCU, onset <18 years). We seek to estimate the suspected EOCU-associated excess odds of experiencing an incident depression spell during adulthood, with comparisons to never cannabis smokers and those with delayed cannabis onset (i.e., not starting to smoke cannabis until adulthood). The National Surveys on Drug Use and Health (NSDUH) assess non-institutionalized community-dwelling residents of the United States after probability sampling each year. In aggregate, the NSDUH analytical sample included 173,775 adult participants from survey years 2005-2009 (74-76% of designated respondents). Standardized computer-assisted interviews collected information on background determinants, age of first cannabis use, and depression spell onset. Logistic regression was used to estimate EOCU-depression spell associations in the form of odds ratios, with statistical adjustment for sex, age, race/ethnicity, years of cannabis involvement, tobacco cigarette onset, and alcohol onset. About 1 in 10 experienced a depression spell during adulthood, and both early-onset and adult-onset cannabis smokers had a modest excess odds of a depression spell compared to never cannabis smokers, even with covariate adjustment (OR=1.7 and 1.8, respectively; both p<0.001). Estimates for early- and adult-onset cannabis smokers did not statistically differ from one another. Shared diathesis that might influence both EOCU and adult-onset depression spell is controlled no more than partially, as will be true until essentially all known early-life shared vulnerabilities are illuminated. Cannabis smoking initiated at any age signals a modest increased risk of a spell of depression in adulthood, even when adjusted for suspected confounding variables studied here. Delaying cannabis onset until adulthood does not appear to diminish the cannabis-associated risk. Copyright © 2011

Are early-onset cannabis smokers at an increased risk of depression spells?

PubMed Central

Fairman, Brian J.; Anthony, James C.

2012-01-01

Background A recent research focus is a set of hypothesized adult-onset mental health disturbances possibly due to early-onset cannabis use (EOCU, onset <18 years). We seek to estimate the suspected EOCU-associated excess odds of experiencing an incident depression spell during adulthood, with comparisons to never cannabis smokers and those with delayed cannabis onset (i.e., not starting to smoke cannabis until adulthood). Methods The National Surveys on Drug Use and Health (NSDUH) assess non-institutionalized community-dwelling residents of the United States after probability sampling each year. In aggregate, the NSDUH analytical sample included 173,775 adult participants from survey years 2005–2009 (74–76% of designated respondents). Standardized computer-assisted interviews collected information on background determinants, age of first cannabis use, and depression spell onset. Logistic regression was used to estimate EOCU-depression spell associations in the form of odds ratios, with statistical adjustment for sex, age, race/ethnicity, years of cannabis involvement, tobacco cigarette onset, and alcohol onset. Results About 1 in 10 experienced a depression spell during adulthood, and both early-onset and adult-onset cannabis smokers had a modest excess odds of a depression spell compared to never cannabis smokers, even with covariate adjustment (OR = 1.7 & 1.8, respectively; both p<0.001). Estimates for early- and adult-onset cannabis smokers did not statistically differ from one another. Limitations Shared diathesis that might influence both EOCU and adult-onset depression spell is controlled no more than partially, as will be true until essentially all known early-life shared vulnerabilities are illuminated. Conclusion Cannabis smoking initiated at any age signals a modest increased risk of a spell of depression in adulthood, even when adjusted for suspected confounding variables studied here. Delaying cannabis onset until adulthood does not appear to

Adult-onset glutaric aciduria type I presenting with white matter abnormalities and subependymal nodules.

PubMed

Pierson, T M; Nezhad, Mani; Tremblay, Matthew A; Lewis, Richard; Wong, Derek; Salamon, Noriko; Sicotte, Nancy

2015-10-01

A 55-year-old female presented with a 6-year history of paresthesias, incontinence, spasticity, and gait abnormalities. Neuroimaging revealed white matter abnormalities associated with subependymal nodules. Biochemical evaluation noted increased serum C5-DC glutarylcarnitines and urine glutaric and 3-hydroxyglutaric acids. Evaluation of the glutaryl-CoA dehydrogenase (GCDH) gene revealed compound heterozygosity consisting of a novel variant (c.1219C>G; p.Leu407Val) and pathogenic mutation (c.848delT; p.L283fs). Together, these results were consistent with a diagnosis of adult-onset type I glutaric aciduria.

A model to predict the onset of non-alcoholic fatty liver disease within 2 years in elderly adults.

PubMed

Lin, Ya-Jie; Gao, Xi-Mei; Pan, Wei-Wei; Gao, Shuai; Yu, Zhen-Zhen; Xu, Ping; Fan, Xiao-Peng

2017-10-01

Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic hepatitis, which leads to cirrhosis and hepatocellular carcinoma. However, it is difficult to identify subjects at high risk for NAFLD onset. This study aims to construct a model to predict the onset of NAFLD within 2 years in elderly adults. This study included and followed 3378 initial NAFLD-free subjects aged 60 years or over for 2 years, which were randomly divided into a training set and a validation set. NAFLD was diagnosed on ultrasound. Clinical and laboratory data were recorded at baseline. A model was constructed in the training set to predict the onset of NAFLD and validated in the validation set. Body mass index, hemoglobin, fasting blood glucose, and triglycerides were identified as predictors for the onset of NAFLD. A risk score (R) was calculated by them. It classified the subjects into low-risk group (R ≤ -2.88), moderate-risk group (-2.88 < R ≤ -1.26), and high-risk group (R > -1.26). In the training set, 4.68% of the participants in the low-risk group, 11.59% of the participants in the moderate-risk group, and 31.02% of the participants in the high-risk group developed NAFLD. In the validation set, 5.84% of the participants in the low-risk group, 10.57% of the participants in the moderate-risk group, and 29.44% of the participants in the high-risk group developed NAFLD. This study developed a model to predict the onset of NAFLD in elderly adults, which might provide indications for intervention to these subjects. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Vibratory onset and offset times in children: A laryngeal imaging study

PubMed Central

Patel, Rita R.

2016-01-01

Objectives The aim of the study was to evaluate the differences in vibratory onset and offset times across age (adult males, adult females, and children) and waveform types (total glottal area waveform, left glottal area waveform, and right glottal area waveform) using high-speed videoendoscopy. Methods In this prospective study, vibratory onset and offset times were evaluated in a total of 86 participants. Forty-three children (23 girls, 18 boys) between 5–11 years and 43 gender matched vocally normal young adults (23 females and 18 males) in the age range (21–45 years) were recruited. Vibratory onset and offset times were calculated in milliseconds from the total, left, and right Glottal Area Waveform (GAW). A two-factor analysis of variance was used to compare the means among the subject groups (children, adult male, and adult female) and waveform type (total GAW, left GAW, right GAW) for onset and offset variables. Post hoc analyses were performed using the Fishers Least Significant Different test with Bonferroni correction for multiple comparisons. Results Children exhibited significantly shorter vibratory onset and offset times compared to adult males and females. Differences in vibratory onset and offset times were not statistically significant between adult males and females. Across all waveform types (i.e. total GAW, left GAW, and right GAW), no statistical significance was observed among the subject groups. Conclusion This is the first study reporting vibratory onset and offset times in the pediatric population. The study findings lay the foundation for the development of a large age- and gender- based database of the pediatric population to aid the study of the effects of maturation of vocal fold vibration in adulthood. The findings from this study may also provide the basis for evaluating the impact of numerous lesions on tissue pliability, and thereby has potential utility for the clinical differentiation of various lesions. PMID:27368436

Examination of validity in spoken language evaluations: Adult onset stuttering following mild traumatic brain injury.

PubMed

Roth, Carole R; Cornis-Pop, Micaela; Beach, Woodford A

2015-01-01

Reports of increased incidence of adult onset stuttering in veterans and service members with mild traumatic brain injury (mTBI) from combat operations in Iraq and Afghanistan lead to a reexamination of the neurogenic vs. psychogenic etiology of stuttering. This article proposes to examine the merit of the dichotomy between neurogenic and psychogenic bases of stuttering, including symptom exaggeration, for the evaluation and treatment of the disorder. Two case studies of adult onset stuttering in service members with mTBI from improvised explosive device blasts are presented in detail. Speech fluency was disrupted by abnormal pauses and speech hesitations, brief blocks, rapid repetitions, and occasional prolongations. There was also wide variability in the frequency of stuttering across topics and conversational situations. Treatment focused on reducing the frequency and severity of dysfluencies and included educational, psychological, environmental, and behavioral interventions. Stuttering characteristics as well as the absence of objective neurological findings ruled out neurogenic basis of stuttering in these two cases and pointed to psychogenic causes. However, the differential diagnosis had only limited value for developing the plan of care. The successful outcomes of the treatment serve to illustrate the complex interaction of neurological, psychological, emotional, and environmental factors of post-concussive symptoms and to underscore the notion that there are many facets to symptom presentation in post-combat health.

Childhood Residential and Agricultural Pesticide Exposures in Relation to Adult-Onset Rheumatoid Arthritis in Women

PubMed Central

Parks, Christine G; Sandler, Dale P

2018-01-01

Abstract Farming and pesticide exposure may influence risk of rheumatoid arthritis (RA); the role of early-life pesticide exposure is unknown. The Sister Study includes a US national cohort of women aged 35–74 years (enrolled 2004–2009); we examined childhood pesticide exposure in women in this cohort with adult-onset RA. Cases (n = 424) were compared with 48,919 noncases. Data included pesticide use at the longest childhood residence through age 14 years, farm residence of at least 12 months with agricultural pesticide exposure through age 18 years, and maternal farm experience. Odds ratios and 95% confidence intervals were adjusted for age, race or ethnicity, education, smoking, and childhood socioeconomic factors. Cases with RA reported more frequent and direct (personal) residential pesticide use in childhood (for infrequent/indirect pesticide use, odds ratio (OR) = 1.1; for frequent/direct use, OR = 1.8; P for trend = 0.013). Compared with women without residential farm history, odds of having RA increased for those reporting a childhood-only farm residence with personal exposure to pesticides used on crops (OR = 1.8, 95% confidence interval: 1.1, 2.9) or livestock (OR = 2.0, 95% confidence interval: 1.2, 3.3). Our findings suggest adult-onset RA may be related to childhood exposure to residential and agricultural pesticides, and support further investigations of lifetime pesticide use in RA. PMID:29020148

Between-day reliability of MyotonPRO for the non-invasive measurement of muscle material properties in the lower extremities of patients with a chronic spinal cord injury.

PubMed

Ko, Chang-Yong; Choi, Hyuk-Jae; Ryu, Jeicheong; Kim, Gyoosuk

2018-05-17

Measuring the muscle properties of patients with spinal cord injuries (SCIs) is important to better understand their biomechanical features. In this study, we sought to evaluate the between-day reliability of MyotonPRO, a handheld device that can measure muscle mechanical properties, and assess whether it is reliable to measure muscle properties over time in patients with SCI. Thirteen men with complete SCIs (age 53.9 ± 6.3 years, height 171.0 ± 5.2 cm, weight 66.1 ± 5.8 kg), and injury levels ranging from L1 to T12, were enrolled. Oscillation frequency; logarithmic decrement; dynamic stiffness; mechanical stress relaxation time; and creep of the biceps femoris, medial and lateral gastrocnemius, rectus femoris, tibialis anterior, and Achilles tendon were measured on consecutive days using MyotonPRO. The intraclass coefficient for most muscles and the Achilles tendon ranged from 0.53 to 0.99 for all parameters. The percentage standard error of the measurement for many parameters in most muscles and the Achilles tendon was less than 10%. Bland-Altman analysis showed a high agreement for all mechanical properties. No significant differences were observed in any muscle or Achilles tendon properties between days (all p > 0.05). These results indicate that the MyotonPRO is reliable for between-day measurements of the mechanical properties of lower limb muscles and Achilles tendon in patients with SCI. Copyright © 2018 Elsevier Ltd. All rights reserved.

Development of a genomic DNA reference material panel for myotonic dystrophy type 1 (DM1) genetic testing.

PubMed

Kalman, Lisa; Tarleton, Jack; Hitch, Monica; Hegde, Madhuri; Hjelm, Nick; Berry-Kravis, Elizabeth; Zhou, Lili; Hilbert, James E; Luebbe, Elizabeth A; Moxley, Richard T; Toji, Lorraine

2013-07-01

Myotonic dystrophy type 1 (DM1) is caused by expansion of a CTG triplet repeat in the 3' untranslated region of the DMPK gene that encodes a serine-threonine kinase. Patients with larger repeats tend to have a more severe phenotype. Clinical laboratories require reference and quality control materials for DM1 diagnostic and carrier genetic testing. Well-characterized reference materials are not available. To address this need, the Centers for Disease Control and Prevention-based Genetic Testing Reference Material Coordination Program, in collaboration with members of the genetic testing community, the National Registry of Myotonic Dystrophy and Facioscapulohumeral Muscular Dystrophy Patients and Family Members, and the Coriell Cell Repositories, has established and characterized cell lines from patients with DM1 to create a reference material panel. The CTG repeats in genomic DNA samples from 10 DM1 cell lines were characterized in three clinical genetic testing laboratories using PCR and Southern blot analysis. DMPK alleles in the samples cover four of five DM1 clinical categories: normal (5 to 34 repeats), mild (50 to 100 repeats), classical (101 to 1000 repeats), and congenital (>1000 repeats). We did not identify or establish Coriell cell lines in the premutation range (35 to 49 repeats). These samples are publicly available for quality control, proficiency testing, test development, and research and should help improve the accuracy of DM1 testing. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

An analysis of the inheritance pattern of an adult-onset hearing loss in Border Collie dogs.

PubMed

Schmutz, Sheila M

2014-01-01

During routine diagnostic BAER testing of dogs of various breeds for private owners at the Western College of Veterinary Medicine in Saskatoon, it became evident that some individual dogs developed hearing loss as adults. Although inherited congenital deafness has been widely reported in dogs, this type of deafness had not. Special clinics were set up to screen working Border Collies at herding competitions. To determine the typical age that geriatric deafness might be expected, retired dogs were also recruited. Five of the 10 Border Collies 12 years of age or older had hearing loss (1 bilaterally deaf and 4 had reduced hearing). The adult onset deafness which exhibited in three families, did not usually occur until 5 years of age, too young to be geriatric deafness. This adult onset deafness fits an autosomal dominant pattern of inheritance. Several of these dogs had been BAER tested at younger ages with no sign of deafness. The deaf dogs were not associated with either gender. A survey was developed which was completed by the dog owners, that indicated that the hearing loss was gradual, not sudden. In addition, some family studies were conducted. Dogs at 5 years of age were often in the prime of their herding careers and then did not respond appropriately to distant commands. This type of deafness is important to dog owners but is also a potential medical model for some forms of hearing loss in humans. This report also suggests that geriatric hearing loss is common in dogs older than 12 years.

Clinically Relevant Cognitive Impairment in Middle-Aged Adults With Childhood-Onset Type 1 Diabetes

PubMed Central

Nunley, Karen A.; Ryan, Christopher M.; Jennings, J. Richard; Aizenstein, Howard J.; Zgibor, Janice C.; Costacou, Tina; Boudreau, Robert M.; Miller, Rachel; Orchard, Trevor J.; Saxton, Judith A.

2015-01-01

OBJECTIVE The aim of this study was to investigate the presence and correlates of clinically relevant cognitive impairment in middle-aged adults with childhood-onset type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS During 2010–2013, 97 adults diagnosed with T1D and aged <18 years (age and duration 49 ± 7 and 41 ± 6 years, respectively; 51% female) and 138 similarly aged adults without T1D (age 49 ± 7 years; 55% female) completed extensive neuropsychological testing. Biomedical data on participants with T1D were collected periodically since 1986–1988. Cognitive impairment status was based on the number of test scores ≥1.5 SD worse than demographically appropriate published norms: none, mild (only one test), or clinically relevant (two or more tests). RESULTS The prevalence of clinically relevant cognitive impairment was five times higher among participants with than without T1D (28% vs. 5%; P < 0.0001), independent of education, age, or blood pressure. Effect sizes were large (Cohen d 0.6–0.9; P < 0.0001) for psychomotor speed and visuoconstruction tasks and were modest (d 0.3–0.6; P < 0.05) for measures of executive function. Among participants with T1D, prevalent cognitive impairment was related to 14-year average A1c >7.5% (58 mmol/mol) (odds ratio [OR] 3.0; P = 0.009), proliferative retinopathy (OR 2.8; P = 0.01), and distal symmetric polyneuropathy (OR 2.6; P = 0.03) measured 5 years earlier; higher BMI (OR 1.1; P = 0.03); and ankle-brachial index ≥1.3 (OR 4.2; P = 0.01) measured 20 years earlier, independent of education. CONCLUSIONS Clinically relevant cognitive impairment is highly prevalent among these middle-aged adults with childhood-onset T1D. In this aging cohort, chronic hyperglycemia and prevalent microvascular disease were associated with cognitive impairment, relationships shown previously in younger populations with T1D. Two additional potentially modifiable risk factors for T1D-related cognitive impairment, vascular health and BMI

Childhood attachment, childhood sexual abuse, and onset of masturbation among adult sexual offenders.

PubMed

Smallbone, Stephen W; McCabe, Billee-Anne

2003-01-01

Written autobiographies of 48 incarcerated adult male sexual offenders (22 rapists, 13 intrafamilial child molesters, and 13 extrafamilial child molesters) were used to generate retrospective self-report measures of their childhood maternal and paternal attachment, childhood sexual abuse experiences, and onset of masturbation. Contrary to expectation, the offenders as a combined group more often reported secure than they did insecure childhood maternal and paternal attachment. There were no differences between the three offender subgroups with respect to maternal attachment; however the rapists and the intrafamilial child molesters were more likely to report insecure paternal attachment than were the extrafamilial child molesters. There were no differences between these offender subgroups in the frequency with which childhood sexual abuse was reported. However, offenders with insecure paternal attachment were more likely to report having been sexually abused than were those with secure paternal attachment. Sexually abused offenders in turn reported earlier onset of masturbation than did those who were not sexually abused. These results are consistent with contemporary attachment models linking insecure childhood attachment to childhood sexual abuse, and with traditional conditioning models linking childhood sexual abuse, early masturbation, and sexual offending.

Effects of age of onset on disease characteristics in non-segmental vitiligo.

PubMed

Solak, Berna; Dikicier, Bahar Sevimli; Cosansu, Nur C; Erdem, Teoman

2017-03-01

In patients with vitiligo, the clinical and laboratory features of the disease may vary according to time of onset. This is addressed in the literature by only a few studies with conflicting results. The aim of this study was to determine the demographic and clinical features of patients with non-segmental vitiligo and to establish the association between vitiligo and autoimmune diseases with a focus on time of disease onset. A total of 224 vitiligo patients for whom complete medical records were available were evaluated retrospectively. Demographic data, scores on the Vitiligo Area Score Index (VASI), clinical features, vitiligo disease activity, repigmentation status, presence of any accompanying autoimmune disease, antinuclear antibody (ANA) titers, serum levels of glucose, thyroid-stimulating hormone (TSH), thyroxine (T4) hormone, anti-thyroid peroxidase (anti-TPO), and anti-thyroglobulin (anti-TG) were recorded. The prevalence of halo nevi was significantly higher (P < 0.001) among children than in other patient groups. The prevalence of leukotrichia was higher in adults with adult-onset disease than in either pediatric patients or adults with childhood-onset disease (P = 0.002). Both anti-TG and anti-TPO levels were significantly higher in adults with adult-onset disease than in pediatric patients and adult patients with childhood-onset disease. The prevalence of autoimmune disease was 22.2%. Anti-TG levels were significantly higher in patients with treatment-related repigmentation than in those without repigmentation. This study shows that clinical features and associations with autoimmune disease may vary according to the age of onset of vitiligo. © 2017 The International Society of Dermatology.

The clinical characteristics and the features of immunophenotype of peripheral lymphocytes of adult onset chronic active Epstein-Barr virus disease at a Tertiary Care Hospital in Beijing.

PubMed

Luo, Ling; Wang, Huanling; Fan, Hongwei; Xie, Jing; Qiu, Zhifeng; Li, Taisheng

2018-03-01

Chronic active Epstein-Barr virus (CAEBV) infection is a rare disease with high mortality. Most of CAEBV patients have been reported from Japan and are pediatric cases.The goal was to describe the clinical characteristics and the immunophenotypic features of peripheral lymphocytes in adult onset CAEBV patients.We retrospectively reviewed and analyzed all adult onset CAEBV cases admitted to Peking Union Medical College Hospital (PUMCH) between 2012 and 2016. Demographic, clinical, laboratory data, and the immunophentyping data of peripheral lymphocytes were collected.There were 28 adult onset CAEBV patients. The median age was 45 (range, 20-81). Most of the patients presented with fever; splenomegaly; lymphadenopathy and hepatitis. Unlike pediatric cases reported, the manifestations of cardiovascular diseases in our patients were pulmonary arterial hypertension, decreased cardiac function and aorta vasculitis. Prevalence of interstitial pneumonitis in our patients were comparatively higher and prevalence of hypersensitivity to mosquito bites were comparatively lower than that reported by Japan. In this study, CAEBV patients had decreased B cell, NK cell, CD4 cell and CD8 cell counts. The prevalence of low level of B cells, NK cells, CD4 cells was relatively higher than reported ever.Chinese adult onset CAEBV patients have different clinical characteristics and are featured by an immunosuppression status as demonstrated by decreased B cell, NK cell, CD4 cell and CD8 cell.

The clinical characteristics and the features of immunophenotype of peripheral lymphocytes of adult onset chronic active Epstein-Barr virus disease at a Tertiary Care Hospital in Beijing

PubMed Central

Luo, Ling; Wang, Huanling; Fan, Hongwei; Xie, Jing; Qiu, Zhifeng; Li, Taisheng

2018-01-01

Abstract Chronic active Epstein-Barr virus (CAEBV) infection is a rare disease with high mortality. Most of CAEBV patients have been reported from Japan and are pediatric cases. The goal was to describe the clinical characteristics and the immunophenotypic features of peripheral lymphocytes in adult onset CAEBV patients. We retrospectively reviewed and analyzed all adult onset CAEBV cases admitted to Peking Union Medical College Hospital (PUMCH) between 2012 and 2016. Demographic, clinical, laboratory data, and the immunophentyping data of peripheral lymphocytes were collected. There were 28 adult onset CAEBV patients. The median age was 45 (range, 20–81). Most of the patients presented with fever; splenomegaly; lymphadenopathy and hepatitis. Unlike pediatric cases reported, the manifestations of cardiovascular diseases in our patients were pulmonary arterial hypertension, decreased cardiac function and aorta vasculitis. Prevalence of interstitial pneumonitis in our patients were comparatively higher and prevalence of hypersensitivity to mosquito bites were comparatively lower than that reported by Japan. In this study, CAEBV patients had decreased B cell, NK cell, CD4 cell and CD8 cell counts. The prevalence of low level of B cells, NK cells, CD4 cells was relatively higher than reported ever. Chinese adult onset CAEBV patients have different clinical characteristics and are featured by an immunosuppression status as demonstrated by decreased B cell, NK cell, CD4 cell and CD8 cell. PMID:29489682

Factors Associated with the Incidence and Severity of New-Onset Atrial Fibrillation in Adult Critically Ill Patients

PubMed Central

Leichtweis, Gustavo Elias; Andriolo, Luiza; Delevatti, Yasmim A.; Jorge, Amaury C.; Fumagalli, Andreia C.; Santos, Luiz Claudio; Miura, Cecilia K.; Saito, Sergio K.

2017-01-01

Background Acute Atrial Fibrillation (AF) is common in critically ill patients, with significant morbidity and mortality; however, its incidence and severity in Intensive Care Units (ICUs) from low-income countries are poorly studied. Additionally, impact of vasoactive drugs on its incidence and severity is still not understood. This study aimed to assess epidemiology and risk factors for acute new-onset AF in critically ill adult patients and the role of vasoactive drugs. Method Cohort performed in seven general ICUs (including cardiac surgery) in three cities in Paraná State (southern Brazil) for 45 days. Patients were followed until hospital discharge. Results Among 430 patients evaluated, the incidence of acute new-onset AF was 11.2%. Patients with AF had higher ICU and hospital mortality. Vasoactive drugs use (norepinephrine and dobutamine) was correlated with higher incidence of AF and higher mortality in patients with AF; vasopressin (though used in few patients) had no effect on development of AF. Conclusions In general ICU patients, incidence of new-onset AF was 11.2% with a high impact on morbidity and mortality, particularly associated with the presence of Acute Renal Failure. The use of vasoactive drugs (norepinephrine and dobutamine) could lead to a higher incidence of new-onset AF-associated morbidity and mortality. PMID:28702263

Factors Associated with the Incidence and Severity of New-Onset Atrial Fibrillation in Adult Critically Ill Patients.

PubMed

Duarte, Péricles A D; Leichtweis, Gustavo Elias; Andriolo, Luiza; Delevatti, Yasmim A; Jorge, Amaury C; Fumagalli, Andreia C; Santos, Luiz Claudio; Miura, Cecilia K; Saito, Sergio K

2017-01-01

Acute Atrial Fibrillation (AF) is common in critically ill patients, with significant morbidity and mortality; however, its incidence and severity in Intensive Care Units (ICUs) from low-income countries are poorly studied. Additionally, impact of vasoactive drugs on its incidence and severity is still not understood. This study aimed to assess epidemiology and risk factors for acute new-onset AF in critically ill adult patients and the role of vasoactive drugs. Cohort performed in seven general ICUs (including cardiac surgery) in three cities in Paraná State (southern Brazil) for 45 days. Patients were followed until hospital discharge. Among 430 patients evaluated, the incidence of acute new-onset AF was 11.2%. Patients with AF had higher ICU and hospital mortality. Vasoactive drugs use (norepinephrine and dobutamine) was correlated with higher incidence of AF and higher mortality in patients with AF; vasopressin (though used in few patients) had no effect on development of AF. In general ICU patients, incidence of new-onset AF was 11.2% with a high impact on morbidity and mortality, particularly associated with the presence of Acute Renal Failure. The use of vasoactive drugs (norepinephrine and dobutamine) could lead to a higher incidence of new-onset AF-associated morbidity and mortality.

Opioid-free general anesthesia in patient with Steinert syndrome (myotonic dystrophy): Case report.

PubMed

Gaszynski, Tomasz

2016-09-01

We report on the anesthetic management using opioid-free method of a patient with Steinert syndrome (myotonic dystrophy, MD), autosomal dominant dystrophy which is characterized by consistent contracture of muscle following stimulation. A myotonic crisis can be induced by numerous factors including hypothermia, shivering, and mechanical or electrical stimulation. In patients with MD, hypersensitivity to anesthetic drugs, especially muscle relaxants and opioids, may complicate postoperative management. If opioids are employed (systemic or neuraxial), then ICU care and continuous pulse oximetry must be considered given the high risk for respiratory depression and aspiration. Patients with MD present high sensitivity to the usual anesthetics such as volatile and muscle relaxants (both depolarizing and nondepolarizing). Opioids may induce muscle rigidity in this type of MD. Therefore, omitting opioids is recommended. Due to hypersensitivity to opioids and increased susceptibility to intra- and postoperative complications, it is recommended to introduce opioid-free anesthesia (OFA), for example, with use of dexmedetomidine (DEX). This is a new method of conducting general anesthesia without opioids and is based on concept of multimodal approach to pain management. A 31-year-old male patient (183 cm, 69 kg) was scheduled for laparoscopic operation of cholecystectomy. The patient received intravenously (IV): propofol in a dose of 250 mg followed by continuous infusion, rocuronium in a dose of 20 mg, and DEX in a loading dose of 0.6 μg/kg over 10 minutes followed by continuous infusion of dose of 0.2 μg/kg/hour. The course of anesthesia and postoperative period were uneventful. The patient exited the operating theatre in a good medical state, with vitals within normal limits and fully regained consciousness. DEX is effective and safe for moderately painful procedures in patients with the elevated risk of respiratory and cardiovascular failure. This

Effect of adult onset hypothyroidism on behavioral parameters and acetylcholinesterase isoforms activity in specific brain regions of male mice.

PubMed

Vasilopoulou, Catherine G; Constantinou, Caterina; Giannakopoulou, Dimitra; Giompres, Panagiotis; Margarity, Marigoula

2016-10-01

Thyroid hormones (TH) are essential for normal development and function of mammalian central nervous system (CNS); TH dysregulation has been implicated in several cognitive and behavioral deficits related to dysfunctions of neurotransmitter systems. In the present study, we investigated the effects of adult onset hypothyroidism on the activity of acetylcholinesterase (AChE) and on related behavioral parameters. For this purpose we used adult male Balb/cJ mice that were divided randomly into euthyroid and hypothyroid animal groups. Animals were rendered hypothyroid through administration of 1% w/v KClO4 in their drinking water for 8weeks. At the end of the treatment, learning/memory procedures were examined through step-through passive avoidance task while fear/anxiety was assessed using elevated plus-maze (EPM) and open-field (OF) tests. AChE activity was determined colorimetrically in two different fractions, salt-soluble fraction (SS) (containing mainly the G1 isoform) and detergent-soluble fraction (DS) (containing mainly the G4 isoform) in cerebral cortex, cerebellum, midbrain, hippocampus and striatum. Our results indicate that adult onset hypothyroidism caused significant memory impairment and increased fear/anxiety. Moreover, the activity of both isoforms of AChE was reduced in all brain regions examined in a brain region- and isoform-specific manner. Copyright © 2016. Published by Elsevier Inc.

Adult-onset opsoclonus-myoclonus syndrome due to West Nile Virus treated with intravenous immunoglobulin.

PubMed

Hébert, Julien; Armstrong, David; Daneman, Nick; Jain, Jennifer Deborah; Perry, James

2017-02-01

A 63-year-old female with no significant past medical history was presented with a 5-day history of progressive opsoclonus-myoclonus, headaches, and fevers. Her workup was significant only for positive West-Nile Virus serum serologies. She received a 2-day course of intravenous immunoglobulin (IvIG). At an 8-week follow up, she had a complete neurological remission. Adult-onset opsoclonus-myoclonus syndrome is a rare condition for which paraneoplastic and infectious causes have been attributed. To our knowledge, this is the first case reported of opsoclonus-myoclonus secondary to West-Nile Virus treated with intravenous immunoglobulin monotherapy.

Adult onset Hallervorden-Spatz disease with psychotic symptoms.

PubMed

del Valle-López, Pilar; Pérez-García, Rosa; Sanguino-Andrés, Rosa; González-Pablos, Emilio

2011-01-01

Hallervorden-Spatz disease is a rare neurological disorder characterized by pyramidal and extrapyramidal manifestations, dysarthria and dementia. Its onset is usually in childhood and most patients have a fatal outcome in few years. A high percentage of cases are hereditary with a recessive autosomal pattern. In the majority of the patients reported, a mutation of the gene that encodes the pantothenate kinase (PANK2) located in the 20p13-p12.3 chromosome that causes iron storage in the basal ganglia of the brain has been found. Its diagnosis is based on clinical symptoms as well as specific MRI imaging findings. The most common psychiatric features are cognitive impairment as well as depressive symptoms. There are few documented cases with psychotic disorders. We present the case of a patient with late onset Hallervorden-Spatz disease and psychotic symptoms that preceded the development of neurological manifestations. The pathophysiology and the treatment of psychotic symptomatology are presented and discussed. Key words: Psicosis, Hallervorden-Spatz, late onset, Basal ganglia.

Sexuality Education and Implications for Quality of Care for Individuals with Adult Onset Disability: A Review of Current Literature

ERIC Educational Resources Information Center

Eglseder, Kate; Webb, Sheridan

2017-01-01

Purpose: To investigate the need for sexuality education for individuals with adult onset physical disabilities as it relates to quality of life and to identify current trends in the provision of sexuality education by health care providers relating to quality of care. Data Sources: Literature review from January 1986 to December 2016. Study…

Adult-onset hyperinsulinaemic hypoglycaemia in clinical practice: diagnosis, aetiology and management.

PubMed

Challis, Benjamin G; Powlson, Andrew S; Casey, Ruth T; Pearson, Carla; Lam, Brian Y; Ma, Marcella; Pitfield, Deborah; Yeo, Giles S H; Godfrey, Edmund; Cheow, Heok K; Chatterjee, V Krishna; Carroll, Nicholas R; Shaw, Ashley; Buscombe, John R; Simpson, Helen L

2017-10-01

In adults with hyperinsulinaemic hypoglycaemia (HH), in particular those with insulinoma, the optimal diagnostic and management strategies remain uncertain. Here, we sought to characterise the biochemical and radiological assessment, and clinical management of adults with HH at a tertiary centre over a thirteen-year period. Clinical, biochemical, radiological and histological data were reviewed from all confirmed cases of adult-onset hyperinsulinaemic hypoglycaemia at our centre between 2003 and 2016. In a subset of patients with stage I insulinoma, whole-exome sequencing of tumour DNA was performed. Twenty-nine patients were identified (27 insulinoma, including 6 subjects with metastatic disease; 1 pro-insulin/GLP-1 co-secreting tumour; 1 activating glucokinase mutation). In all cases, hypoglycaemia (glucose ≤2.2 mmol/L) was achieved within 48 h of a supervised fast. At fast termination, subjects with stage IV insulinoma had significantly higher insulin, C-peptide and pro-insulin compared to those with insulinoma staged I-IIIB. Preoperative localisation of insulinoma was most successfully achieved with EUS. In two patients with inoperable, metastatic insulinoma, peptide receptor radionuclide therapy (PRRT) with 177 Lu-DOTATATE rapidly restored euglycaemia and lowered fasting insulin. Finally, in a subset of stage I insulinoma, whole-exome sequencing of tumour DNA identified the pathogenic Ying Yang-1 ( YY1 ) somatic mutation (c.C1115G/p.T372R) in one tumour, with all tumours exhibiting a low somatic mutation burden. Our study highlights, in particular, the utility of the 48-h fast in the diagnosis of insulinoma, EUS for tumour localisation and the value of PRRT therapy in the treatment of metastatic disease. © 2017 The authors.

Big Five personality and depression diagnosis, severity and age of onset in older adults.

PubMed

Koorevaar, A M L; Comijs, H C; Dhondt, A D F; van Marwijk, H W J; van der Mast, R C; Naarding, P; Oude Voshaar, R C; Stek, M L

2013-10-01

Personality may play an important role in late-life depression. The aim of this study is to examine the association between the Big Five personality domains and the diagnosis, severity and age of onset of late-life depression. The NEO-Five Factor Inventory (NEO-FFI) was cross-sectionally used in 352 depressed and 125 non-depressed older adults participating in the Netherlands Study of Depression in Older Persons (NESDO). Depression diagnosis was determined by the Composite International Diagnostic Interview (CIDI). Severity of depression was assessed by the Inventory of Depressive Symptomatology (IDS). Logistic and linear regression analyses were applied. Adjustments were made for sociodemographic, cognitive, health and psychosocial variables. Both the presence of a depression diagnosis and severity of depression were significantly associated with higher Neuroticism (OR=1.35, 95% CI=1.28-1.43 and B=1.06, p<.001, respectively) and lower Extraversion (OR=.79, 95% CI=.75-.83; B=-.85, p<.001) and Conscientiousness (OR=.86, 95% CI=.81.-.90; B=-.86, p<.001). Earlier onset of depression was significantly associated with higher Openness (B=-.49, p=.026). Due to the cross-sectional design, no causal inferences can be drawn. Further, current depression may have influenced personality measures. This study confirms an association between personality and late-life depression. Remarkable is the association found between high Openness and earlier age of depression onset. © 2013 Elsevier B.V. All rights reserved.

Age at onset versus family history and clinical outcomes in 1,665 international bipolar-I disorder patients

PubMed Central

BALDESSARINI, ROSS J.; TONDO, LEONARDO; VAZQUEZ, GUSTAVO H.; UNDURRAGA, JUAN; BOLZANI, LORENZA; YILDIZ, AYSEGUL; KHALSA, HARI-MANDIR K.; LAI, MASSIMO; LEPRI, BEATRICE; LOLICH, MARIA; MAFFEI, PIER MARIO; SALVATORE, PAOLA; FAEDDA, GIANNI L.; VIETA, EDUARD; MAURICIO, TOHEN

2012-01-01

Early onset in bipolar disorder (BPD) has been associated with greater familial risk and unfavorable clinical outcomes. We pooled data from seven international centers to analyze the relationships of family history and symptomatic as well as functional measures of adult morbidity to onset age, or onset in childhood (age <12), adolescence (12-18), or adulthood (19-55 years). In 1,665 adult, DSM-IV BPD-I patients, onset was 5% in childhood, 28% in adolescence, and 53% at peak ages 15-25. Adolescent and adult onset did not differ by symptomatic morbidity (episodes/year, percentage of months ill, co-morbidity, hospitalization, suicide attempts) or family history. Indications of favorable adult functional outcomes (employment, living independently, marriage and children, and a composite measure including education) ranked, by onset: adult > adolescent > child. Onset in childhood versus adolescence had more episodes/year and more psychiatric co-morbidity. Family history was most prevalent with childhood onset, similar over onset ages 12-40 years, and fell sharply thereafter. Multivariate modeling sustained the impression that family history and poor functional, but not symptomatic, outcomes were associated with younger, especially childhood onset. Early onset was more related to poor functional outcomes than greater symptomatic morbidity, with least favorable outcomes and greater family history with childhood onset. PMID:22295008

Childhood-onset HAM/TSP with progressive cognitive impairment.

PubMed

Zorzi, Giovanna; Mancuso, Roberta; Nardocci, Nardo; Farina, Laura; Guerini, Franca Rosa; Ferrante, Pasquale

2010-04-01

HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic myelopathy, usually with adult-onset. Very few cases of childhood-onset have been described, most presenting with progressive paraparesis and sphincteric disturbances as in the adult form. Here we report a young male with childhood-onset of HAM/TSP and progressive cognitive and behavioral disturbances. A serological screening revealed HTLV-I infection, confirmed by Western Immunoblotting analysis. Molecular characterization of amplified HTLV-I proviral DNA has been performed both in the patient and his mother by LTR sequence analysis, and HLA genotype inheritance was evaluated. Our case indicates the possibility that cognitive dysfunctions may be one manifestation of HTLV-I infection in childhood.

Childhood-compared to adolescent-onset bipolar disorder has more statistically significant clinical correlates.

PubMed

Holtzman, Jessica N; Miller, Shefali; Hooshmand, Farnaz; Wang, Po W; Chang, Kiki D; Hill, Shelley J; Rasgon, Natalie L; Ketter, Terence A

2015-07-01

The strengths and limitations of considering childhood-and adolescent-onset bipolar disorder (BD) separately versus together remain to be established. We assessed this issue. BD patients referred to the Stanford Bipolar Disorder Clinic during 2000-2011 were assessed with the Systematic Treatment Enhancement Program for BD Affective Disorders Evaluation. Patients with childhood- and adolescent-onset were compared to those with adult-onset for 7 unfavorable bipolar illness characteristics with replicated associations with early-onset patients. Among 502 BD outpatients, those with childhood- (<13 years, N=110) and adolescent- (13-18 years, N=218) onset had significantly higher rates for 4/7 unfavorable illness characteristics, including lifetime comorbid anxiety disorder, at least ten lifetime mood episodes, lifetime alcohol use disorder, and prior suicide attempt, than those with adult-onset (>18 years, N=174). Childhood- but not adolescent-onset BD patients also had significantly higher rates of first-degree relative with mood disorder, lifetime substance use disorder, and rapid cycling in the prior year. Patients with pooled childhood/adolescent - compared to adult-onset had significantly higher rates for 5/7 of these unfavorable illness characteristics, while patients with childhood- compared to adolescent-onset had significantly higher rates for 4/7 of these unfavorable illness characteristics. Caucasian, insured, suburban, low substance abuse, American specialty clinic-referred sample limits generalizability. Onset age is based on retrospective recall. Childhood- compared to adolescent-onset BD was more robustly related to unfavorable bipolar illness characteristics, so pooling these groups attenuated such relationships. Further study is warranted to determine the extent to which adolescent-onset BD represents an intermediate phenotype between childhood- and adult-onset BD. Copyright © 2015 Elsevier B.V. All rights reserved.

A Population-based survey of risk for cancer in individuals diagnosed with myotonic dystrophy

PubMed Central

Abbott, Diana; Johnson, Nicholas E; Cannon-Albright, Lisa A.

2018-01-01

Introduction The risk of cancer in patients diagnosed with myotonic dystrophy (DM) is reported for the homogeneous Utah population. Methods Clinical data accessed from the largest Utah healthcare providers have been record-linked to the Utah Population Database (UPDB), a population-based resource also linked to the Utah Cancer Registry. Relative risks were estimated for 36 cancers of different types in 281 DM patients. Results Testicular cancer (RR=10.74; 95% CI: 1.91, 38.79), endometrial cancer (6.98; 1.24, 25.22), and Non-Hodgkins lymphoma (4.25; 1.16, 12.43) were all observed at significant excess in DM patients. Discussion This study confirms an overall increased risk of cancer in DM. Individuals diagnosed with DM might benefit from risk counseling. PMID:27064430

Perceived barriers to and facilitators of physical activity in young adults with childhood-onset physical disabilities.

PubMed

Buffart, Laurien M; Westendorp, Tessa; van den Berg-Emons, Rita J; Stam, Henk J; Roebroeck, Marij E

2009-11-01

To explore the main barriers to and facilitators of physical activity in young adults with childhood-onset physical disabilities. Qualitative study using focus groups. Sixteen persons (12 men and 4 women) aged 22.4 (standard deviation 3.4) years, of whom 50% were wheelchair-dependent, participated in the study. Eight were diagnosed with myelomeningocele, 4 with cerebral palsy, 2 with acquired brain injury and 2 with rheumatoid arthritis. Three focus group sessions of 1.5 h were conducted using a semi-structured question route to assess perceived barriers to and facilitators of physical activity. Tape recordings were transcribed verbatim and content analysed. According to the Physical Activity for People with a Physical Disability model, barriers and facilitators were subdivided into personal factors and environmental factors. Participants reported several barriers related to attitude and motivation. In addition, lack of energy, existing injury or fear of developing injuries or complications, limited physical activity facilities, and lack of information and knowledge, appeared to be barriers to physical activity. Fun and social contacts were mentioned as facilitators of engaging in physical activity, as well as improved health and fitness. Young adults with childhood-onset physical disabilities perceived various personal and environmental factors as barriers to or facilitators of physical activity. These should be taken into account when developing interventions to promote physical activity in this population.

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…

Progressive myoclonic epilepsy as an adult-onset manifestation of Leigh syndrome due to m.14487T>C.

PubMed

Dermaut, B; Seneca, S; Dom, L; Smets, K; Ceulemans, L; Smet, J; De Paepe, B; Tousseyn, S; Weckhuysen, S; Gewillig, M; Pals, P; Parizel, P; De Bleecker, J L; Boon, P; De Meirleir, L; De Jonghe, P; Van Coster, R; Van Paesschen, W; Santens, P

2010-01-01

m.14487T>C, a missense mutation (p.M63V) affecting the ND6 subunit of complex I of the mitochondrial respiratory chain, has been reported in isolated childhood cases with Leigh syndrome (LS) and progressive dystonia. Adult-onset phenotypes have not been reported. To determine the clinical-neurological spectrum and associated mutation loads in an extended m.14487T>C family. A genotype-phenotype correlation study of a Belgian five-generation family with 12 affected family members segregating m.14487T>C was carried out. Clinical and mutation load data were available for nine family members. Biochemical analysis of the respiratory chain was performed in three muscle biopsies. Heteroplasmic m.14487T>C levels (36-52% in leucocytes, 97-99% in muscle) were found in patients with progressive myoclonic epilepsy (PME) and dystonia or progressive hypokinetic-rigid syndrome. Patients with infantile LS were homoplasmic (99-100% in leucocytes, 100% in muscle). We found lower mutation loads (between 8 and 35% in blood) in adult patients with clinical features including migraine with aura, Leber hereditary optic neuropathy, sensorineural hearing loss and diabetes mellitus type 2. Despite homoplasmic mutation loads, complex I catalytic activity was only moderately decreased in muscle tissue. m.14487T>C resulted in a broad spectrum of phenotypes in our family. Depending on the mutation load, it caused severe encephalopathies ranging from infantile LS to adult-onset PME with dystonia. This is the first report of PME as an important neurological manifestation of an isolated mitochondrial complex I defect.

The Role of the Atrial Electromechanical Delay in Predicting Atrial Fibrillation in Myotonic Dystrophy Type 1 Patients.

PubMed

Russo, Vincenzo; Rago, Anna; Ciardiello, Carmine; Russo, Maria Giovanna; Calabrò, Paolo; Politano, Luisa; Nigro, Gerardo

2016-01-01

Paroxysmal atrial tachyarrhythmias frequently occur in myotonic dystrophy type 1 (DM1) patients. The aim of the current study was to evaluate the atrial electromechanical-delay (AEMD) in a DM1-population with normal cardiac function and its relationship to atrial fibrillation (AF) onset. Fifty DM1 patients (28 male; mean age 34.2 ± 11.4 years) and 50 healthy subjects used as controls, matched for age and gender, were studied for the occurrence of atrial fibrillation during a 4-year follow-up, through 30-day external loop recorder (ELR) monitoring performed every 6 months. Intra-AEMD and inter-AEMD of both atrium were measured through tissue-Doppler echocardiography. Compared to the healthy control group, the DM1 group showed a statistically significant increase in inter-AEMD and intraleft-AEMD. Dividing the DM1-group into 2 subgroups (patients with or without AF), the inter-AEMD and intraleft-AEMD were significantly higher in the subgroup with AF compared to the subgroup without AF. A cut off value of 39.2 milliseconds for intraleft-AEMD had a sensitivity of 90% and a specificity of 90% in identifying DM1 patients with AF risk. A cut off value of 57.7 milliseconds for inter-AEMD had a sensitivity of 84.2% and a specificity of 93.5% in identifying this category of patients. Our results showed that the echocardiographic atrial electromechanical delay indices (intraleft and inter-AEMD) were significantly increased in DM1 subjects with normal cardiac function. Intraleft and inter-AEMD represent noninvasive, inexpensive, useful and simple parameters to assess the AF risk in DM1 patients. © 2015 Wiley Periodicals, Inc.

Onset Time of Inhibition of Return is a Promising Index for Assessing Cognitive Functions in Older Adults.

PubMed

Li, Tingni; Wang, Lei; Huang, Wanyi; Zhen, Yanfen; Zhong, Chupeng; Qu, Zhe; Ding, Yulong

2018-06-06

Developing efficient tools for assessing general cognitive functions in older adults is essential. Previous studies found that inhibition of return (IOR) occurred later in the older adults than in the younger (e.g., Castel, Chasteen, Scialfa, & Pratt, 2003). However, little is known about the relationship between the onset time of IOR (IOR-OT) and cognitive functions in the aging population. The present study examined this issue and investigated the potential of using IOR-OT as an index of cognitive functioning in older adults. In two studies, the IOR-OT of healthy younger and older adults was measured by a modified Posner peripheral cueing task, and cognitive functions of the older adults were evaluated with the Addenbrooke's Cognitive Examination Revised (ACE-R). Both studies showed a significant correlation (r = ~0.5) between IOR-OT and cognitive functions as assessed by ACE-R in older individuals: later IOR-OT was accompanied by a lower ACE-R score. To our knowledge, the present studies are the first to discover a relatively strong correlation between IOR-OT and cognitive functions in older adults. These findings provide new evidence supporting the inhibition deficit theory of aging and lay the foundation of using IOR-OT as an objective measure of cognitive functions in the aging population.

An adult-onset case of chronic active Epstein-Barr virus infection with fulminant clinical course.

PubMed

Kaneko, Hiroto; Taniwaki, Masafumi; Matsumoto, Yosuke; Yoshida, Mihoko; Shimura, Kazuho; Fujino, Takahiro; Uchiyama, Hitoji; Kuroda, Junya

2018-06-01

A 56-year-old Japanese male with chronic active Epstein-Barr virus (EBV) infection (CAEBV) who developed systemic gamma-delta T-cell lymphoproliferative disease (LPD) is reported. Although immune cooling therapy was effective, he died of sudden and severe hypoxia and anemia soon after the initiation of cytotoxic chemotherapy that had been previously recommended. There might remain a difficulty to control fulminant adult-onset CAEBV. Additionally, we describe three types of lymphoid cells that were observed in his peripheral blood: morphologically normal lymphocytes, large blastic cells and mature ones with rough granules. Morphological observation appeared to be useful to estimate clinical manifestations. Since CAEBV is extremely rare disease in adult population, it is important to accumulate clinical data to more understand the pathogenesis or to establish treatment strategy. Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Aetiology of Bacteraemia as a Risk Factor for Septic Shock at the Onset of Febrile Neutropaenia in Adult Cancer Patients

PubMed Central

Rosa, Regis Goulart; Goldani, Luciano Zubaran

2014-01-01

Septic shock (SS) at the onset of febrile neutropaenia (FN) is an emergency situation that is associated with high morbidity and mortality. The impact of the specific aetiology of bloodstream infections (BSIs) in the development of SS at the time of FN is not well established. The aim of this study was to evaluate the association between the aetiology of BSIs and SS at the time of FN in hospitalised adult cancer patients. This prospective cohort study was performed at a single tertiary hospital from October 2009 to August 2011. All adult cancer patients admitted consecutively to the haematology ward with FN were evaluated. A stepwise logistic regression was conducted to verify the association between the microbiological characteristics of BSIs and SS at the onset of FN. In total, 307 cases of FN in adult cancer patients were evaluated. There were 115 cases with documented BSI. A multivariate analysis showed that polymicrobial bacteraemia (P = 0.01) was associated with SS. The specific blood isolates independently associated with SS were viridans streptococci (P = 0.02) and Escherichia coli (P = 0.01). Neutropaenic cancer patients with polymicrobial bacteraemia or BSI by viridans streptococci or Escherichia coli are at increased risk for SS at the time of FN. PMID:24804223

Reversal of RNA missplicing and myotonia after muscleblind overexpression in a mouse poly(CUG) model for myotonic dystrophy

PubMed Central

Kanadia, Rahul N.; Shin, Jihae; Yuan, Yuan; Beattie, Stuart G.; Wheeler, Thurman M.; Thornton, Charles A.; Swanson, Maurice S.

2006-01-01

RNA-mediated pathogenesis is a recently developed disease model that proposes that certain types of mutant genes produce toxic transcripts that inhibit the activities of specific proteins. This pathogenesis model was proposed first for the neuromuscular disease myotonic dystrophy (DM), which is associated with the expansion of structurally related (CTG)n and (CCTG)n microsatellites in two unrelated genes. At the RNA level, these expansions form stable hairpins that alter the pre-mRNA splicing activities of two antagonistic factor families, the MBNL and CELF proteins. It is unclear which altered activity is primarily responsible for disease pathogenesis and whether other factors and biochemical pathways are involved. Here, we show that overexpression of Mbnl1 in vivo mediated by transduction of skeletal muscle with a recombinant adeno-associated viral vector rescues disease-associated muscle hyperexcitability, or myotonia, in the HSALR poly(CUG) mouse model for DM. Myotonia reversal occurs concurrently with restoration of the normal adult-splicing patterns of four pre-mRNAs that are misspliced during postnatal development in DM muscle. Our results support the hypothesis that the loss of MBNL1 activity is a primary pathogenic event in the development of RNA missplicing and myotonia in DM and provide a rationale for therapeutic strategies designed either to overexpress MBNL1 or inhibit MBNL1 interactions with CUG and CCUG repeat expansions. PMID:16864772

Adult-onset hypophosphatemic osteomalacia associated with Sjogren syndrome: Clinical case report.

PubMed

Shen, Guohua; Zhang, Yuwei; Hu, Shuang; Liu, Bin; Kuang, Anren

2017-03-01

Hypophosphatemic osteomalacia (HO) is a metabolic bone disease, exhibiting different etiologies such as genetic mutation, tumor induction, dysimmunity, or renal disease. Sjogren's syndrome (SS) is a connective tissue disorder commonly involving exocrine glands; however kidney involvement is also encountered, leading to abnormal phosphorus metabolism, even HO. A 47-year-old female patient presented progressively worsening pain in the chest wall, back and bilateral lower extremities as well as muscle weakness was referred to our department. Due to the laboratory test results, radiographic findings and pathologic results, she was diagnosed with adult-onset HO associated with SS. She was then treated with alkalinization, steroids, neutral phosphate, calcium supplements together with activated vitamin D. So far, she recovered uneventfully with relieved pain and increased serum phosphorus level. HO may be secondary to renal tubular acidosis of SS patients, and it might be a diagnostic challenge when the kidney involvement in SS is latent and precede the typical sicca symptoms.

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

PubMed

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

2009-12-01

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

Fatal coma in a young adult due to late-onset urea cycle deficiency presenting with a prolonged seizure: a case report.

PubMed

Alameri, Majid; Shakra, Mustafa; Alsaadi, Taoufik

2015-11-23

Unexplained hyperammonemic coma in adults can be a medical dilemma in the absence of triggering factors and known comorbidities. Ornithine transcarbamylase deficiency presents most commonly with hyperammonemic coma. Although a rare disorder, ornithine transcarbamylase deficiency is the most common of the urea cycle disorders, which can occur both in children, and less commonly, in adults. The urea cycle disorder is usually acquired as an X-linked trait, and very rarely, similar to our reported case, may be acquired as a "new" mutation. Mutations that lead to later-onset presentations may lead to life-threatening disease and may be unrecognized, particularly when the first clinical symptoms occur in adulthood. We report the case of a previously healthy 17-year-old white man who developed a prolonged seizure and a rapid decline in mental status leading to coma over a 3-day period. Analysis of the OTC gene showed a 119G variant, which was identified in exon 2 of the OTC gene by sequencing. A diagnosis of ornithine transcarbamylase deficiency should be considered in adult patients who present with unexplained hyperammonemic coma and for all adult patients presenting with cryptogenic new-onset seizure and laboratory finding of elevated blood ammonia levels. This reported case highlights the importance of early recognition of this potentially reversible cause of life-threatening encephalopathy, as timely recognition and appropriate treatment can be lifesaving.

Alcohol Drinking Onset: A Reliability Study

ERIC Educational Resources Information Center

Prause, JoAnn; Dooley, David; Ham-Rowbottom, Kathleen A.; Emptage, Nicholas

2007-01-01

Early alcohol drinking onset (ADO) is associated with adult alcohol misuse, but the accuracy of ADO is unclear. Reliability of self-reported ADO was studied in two panels of the National Longitudinal Survey of Youth. For the Adult sample (n = 6,215), the intraclass correlation coefficient (ICC) was 0.36. Older respondents had higher reliabilities…

Transgenerational effects of the endocrine disruptor vinclozolin on the prostate transcriptome and adult onset disease.

PubMed

Anway, Matthew D; Skinner, Michael K

2008-04-01

The ability of an endocrine disruptor exposure during gonadal sex determination to promote a transgenerational prostate disease phenotype was investigated in the current study. Exposure of an F0 gestating female rat to the endocrine disruptor vinclozolin during F1 embryo gonadal sex determination promoted a transgenerational adult onset prostate disease phenotype. The prostate disease phenotype and physiological parameters were determined for males from F1 to F4 generations and the prostate transcriptome was assessed in the F3 generation. Although the prostate in prepubertal animals develops normally, abnormalities involving epithelial cell atrophy, glandular dysgenesis, prostatitis, and hyperplasia of the ventral prostate develop in older animals. The ventral prostate phenotype was transmitted for four generations (F1-F4). Analysis of the ventral prostate transcriptome demonstrated 954 genes had significantly altered expression between control and vinclozolin F3 generation animals. Analysis of isolated ventral prostate epithelial cells identified 259 genes with significantly altered expression between control and vinclozolin F3 generation animals. Characterization of regulated genes demonstrated several cellular pathways were influenced, including calcium and WNT. A number of genes identified have been shown to be associated with prostate disease and cancer, including beta-microseminoprotein (Msp) and tumor necrosis factor receptor superfamily 6 (Fadd). The ability of an endocrine disruptor to promote transgenerational prostate abnormalities appears to involve an epigenetic transgenerational alteration in the prostate transcriptome and male germ-line. Potential epigenetic transgenerational alteration of prostate gene expression by environmental compounds may be important to consider in the etiology of adult onset prostate disease.

Transgenerational Effects of the Endocrine Disruptor Vinclozolin on the Prostate Transcriptome and Adult Onset Disease

PubMed Central

Anway, Matthew D.; Skinner, Michael K.

2018-01-01

PURPOSE The ability of an endocrine disruptor exposure during gonadal sex determination to promote a transgenerational prostate disease phenotype was investigated in the current study. METHODS Exposure of an F0 gestating female rat to the endocrine disruptor vinclozolin during F1 embryo gonadal sex determination promoted a transgenerational adult onset prostate disease phenotype. The prostate disease phenotype and physiological parameters were determined for males from F1 to F4 generations and the prostate transcriptome was assessed in the F3 generation. RESULTS Although the prostate in prepubertal animals develops normally, abnormalities involving epithelial cell atrophy, glandular dysgenesis, prostatitis, and hyperplasia of the ventral prostate develop in older animals. The ventral prostate phenotype was transmitted for four generations (F1–F4). Analysis of the ventral prostate transcriptome demonstrated 954 genes had significantly altered expression between control and vinclozolin F3 generation animals. Analysis of isolated ventral prostate epithelial cells identified 259 genes with significantly altered expression between control and vinclozolin F3 generation animals. Characterization of regulated genes demonstrated several cellular pathways were influenced, including calcium and WNT. A number of genes identified have been shown to be associated with prostate disease and cancer, including beta-microseminoprotein (Msp) and tumor necrosis factor receptor superfamily 6 (Fadd). CONCLUSIONS The ability of an endocrine disruptor to promote transgenerational prostate abnormalities appears to involve an epigenetic transgenerational alteration in the prostate transcriptome and male germ-line. Potential epigenetic transgenerational alteration of prostate gene expression by environmental compounds may be important to consider in the etiology of adult onset prostate disease. PMID:18220299

Adult onset Still's disease accompanied by acute respiratory distress syndrome: A case report.

PubMed

Xi, Xiao-Tu; Wang, Mao-Jie; Huang, Run-Yue; Ding, Bang-Han

2016-09-01

Adult onset Still's disease (AOSD) is a systemic inflammatory disorder characterized by rash, leukocytosis, fever and arthralgia/arthritis. The most common pulmonary manifestations associated with AOSD are pulmonary infiltrates and pleural effusion. The present study describes a 40-year-old male with AOSD who developed fever, sore throat and shortness of breath. Difficulty breathing promptly developed, and the patient was diagnosed with acute respiratory distress syndrome (ARDS). The patient did not respond to antibiotics, including imipenem, vancomycin, fluconazole, moxifloxacin, penicillin, doxycycline and meropenem, but was sensitive to glucocorticoid treatment, including methylprednisolone sodium succinate. ARDS accompanied by AOSD has been rarely reported in the literature. In conclusion, in a patient with ARDS who does not respond to antibiotic treatment, the involvement of AOSD should be considered.

In vitro mapping of Myotonic Dystrophy (DM) gene promoter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Storbeck, C.J.; Sabourin, L.; Baird, S.

1994-09-01

The Myotonic Dystrophy Kinase (DMK) gene has been cloned and shared homology to serine/threonine protein kinases. Overexpression of this gene in stably transfected mouse myoblasts has been shown to inhibit fusion into myotubes while myoblasts stably transfected with an antisense construct show increased fusion potential. These experiments, along with data showing that the DM gene is highly expressed in muscle have highlighted the possibility of DMK being involved in myogenesis. The promoter region of the DM gene lacks a consensus TATA box and CAAT box, but harbours numerous transcription binding sites. Clones containing extended 5{prime} upstream sequences (UPS) of DMKmore » only weakly drive the reporter gene chloramphenicol acetyl transferase (CAT) when transfected into C2C12 mouse myoblasts. However, four E-boxes are present in the first intron of the DM gene and transient assays show increased expression of the CAT gene when the first intron is present downstream of these 5{prime} UPS in an orientation dependent manner. Comparison between mouse and human sequence reveals that the regions in the first intron where the E-boxes are located are highly conserved. The mapping of the promoter and the importance of the first intron in the control of DMK expression will be presented.« less

Children perceive speech onsets by ear and eye*

PubMed Central

JERGER, SUSAN; DAMIAN, MARKUS F.; TYE-MURRAY, NANCY; ABDI, HERVÉ

2016-01-01

Adults use vision to perceive low-fidelity speech; yet how children acquire this ability is not well understood. The literature indicates that children show reduced sensitivity to visual speech from kindergarten to adolescence. We hypothesized that this pattern reflects the effects of complex tasks and a growth period with harder-to-utilize cognitive resources, not lack of sensitivity. We investigated sensitivity to visual speech in children via the phonological priming produced by low-fidelity (non-intact onset) auditory speech presented audiovisually (see dynamic face articulate consonant/rhyme b/ag; hear non-intact onset/rhyme: −b/ag) vs. auditorily (see still face; hear exactly same auditory input). Audiovisual speech produced greater priming from four to fourteen years, indicating that visual speech filled in the non-intact auditory onsets. The influence of visual speech depended uniquely on phonology and speechreading. Children – like adults – perceive speech onsets multimodally. Findings are critical for incorporating visual speech into developmental theories of speech perception. PMID:26752548

Progression rate from new-onset pre-hypertension to hypertension in Korean adults.

PubMed

Kim, Soo Jeong; Lee, Jakyoung; Nam, Chung Mo; Jee, Sun Ha; Park, Il Soo; Lee, Kyung Jong; Lee, Soon Young

2011-01-01

There are limited studies conducted in Asia to investigate the progression rate to hypertension (HTN). This study was done to estimate the progression rate of new-onset pre-HTN (PreHTN) to HTN during an 8-year follow-up period, and to compare the impact of PreHTN on progression to HTN. A total of 49,228 participants, aged 30 to 54 years with new-onset PreHTN at baseline (1994-1996) from a biennial national medical exam were enrolled and followed up every 2 years until 2004. The incidence rate recorded at each interval and the cumulative incidence rate of HTN were analyzed. Hazard ratio of high-normal and high blood pressure (BP) in men and women was calculated. The cumulative incidence rate for high-normal BP was 27.6% and 26.4% at 2-year follow-up, increased to respectively 64.1% and 55.8% in men and women at the 8-year follow-up. Compared to optimal BP, hazard ratios for men with high-normal BP across all age groups were 3- to 4-fold higher at 2-year, and 2- to 3-fold higher at 8-year follow-up. Hazard ratios for women were about 6-fold higher at 2-year and around 4-fold higher at 8-year follow-up. New PreHTN was a significant predisposing factor for future HTN, in young adults and the effect is more prominent in women.

Age-related prevalence of chronic rhinosinusitis and nasal polyps and their relationships with asthma onset.

PubMed

Won, Ha-Kyeong; Kim, Young-Chan; Kang, Min-Gyu; Park, Han-Ki; Lee, Seung-Eun; Kim, Min-Hye; Yang, Min-Suk; Chang, Yoon-Seok; Cho, Sang-Heon; Song, Woo-Jung

2018-04-01

Chronic rhinosinusitis (CRS) is a major disease condition with high morbidity and can influence lower airway disease status in adults. However, its associations with adult asthma onset and activity have not been examined in detail in a general adult population. To investigate relationships between CRS with nasal polyps (CRSwNP) and asthma characteristics. A cross-sectional data set of 17,506 adult participants (≥18 years old) in the Korean National Health and Nutrition Examination Survey from 2010 through 2012 was analyzed. CRS was defined using structured questionnaires according to the international guideline, and presence of nasal polyps was objectively assessed using nasal endoscopy. Presence of asthma and its onset and current activity were assessed using structured questionnaires. CRS was significantly related to asthma, but the relationships were distinct by CRS and asthma status. CRSwNP was significantly associated with adult-onset asthma (onset after 18 years of age) or late-onset asthma (onset after 40 years of age), whereas CRS without nasal polyps was related to childhood-onset asthma (onset before 18 years) or early-onset asthma (onset before 40 years) in adults. The 2 CRS subgroups showed significant associations with current asthma but not with past asthma. However, the comorbid asthma rate was lower than 10% among subjects with CRS. This study found distinct age-related patterns of CRSwNP and asthma and demonstrated their significant associations in a general population. However, the low prevalence of asthma in CRSwNP is in sharp contrast to findings in Western populations, which warrants further investigation for ethnic or regional differences in relationships between CRSwNP and asthma. Copyright © 2018 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

The effect of myotonic dystrophy transcript levels and location on muscle differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mastroyiannopoulos, Nikolaos P.; Chrysanthou, Elina; Kyriakides, Tassos C.

2008-12-12

In myotonic dystrophy type I (DM1), nuclear retention of mutant DMPK transcripts compromises muscle cell differentiation. Although several reports have identified molecular defects in myogenesis, it remains still unclear how exactly the retention of the mutant transcripts induces this defect. We have recently created a novel cellular model in which the mutant DMPK 3' UTR transcripts were released to the cytoplasm of myoblasts by using the WPRE genetic element. As a result, muscle cell differentiation was repaired. In this paper, this cellular model was further exploited to investigate the effect of the levels and location of the mutant transcripts onmore » muscle differentiation. Results show that the levels of these transcripts were proportional to the inhibition of both the initial fusion of myoblasts and the maturity of myotubes. Moreover, the cytoplasmic export of the mutant RNAs to the cytoplasm caused less inhibition only in the initial fusion of myoblasts.« less

Onset Age of Obesity and Variables of Personality and Biography.

ERIC Educational Resources Information Center

Steinberg, Carol

Three hypotheses derived from Hilde Bruch's formulations regarding onset differences among the obese were tested. In Bruch's theory, adult-onset, or reactive, obesity is a result of psychological trauma; the individual uses eating as a defense against anxiety and depression. Child-onset, or developmental, obesity results from a mixture of…

Identify changes of brain regional homogeneity in early and later adult onset patients with first-episode depression using resting-state fMRI.

PubMed

Shen, Zonglin; Jiang, Linling; Yang, Shuran; Ye, Jing; Dai, Nan; Liu, Xiaoyan; Li, Na; Lu, Jin; Liu, Fang; Lu, Yi; Sun, Xuejin; Cheng, Yuqi; Xu, Xiufeng

2017-01-01

Previous work exhibited different brain grey matter volume (GMV) changes between patients with early adult onset depression (EOD, age 18-29) and later adult onset depression (LOD, age 30-44) by using 30-year-old as the cut-off age. To identify whether regional homogeneity (ReHo) changes are also different between EOD and LOD by using same cut-off age, we used resting-state functional magnetic resonance imaging (fMRI) to detect the abnormal ReHo between patients with EOD and LOD in the present study. Resting-state fMRI scans of 58 patients with EOD, 62 patients with LOD, 60 young healthy controls (HC), and 52 old HC were obtained. The ReHo approach was used to analyze the images. The ANOVA analysis revealed that the ReHo values in the frontoparietal, occipital, and cerebellar regions were significantly different among the four groups. Relative to patients with LOD, patients with EOD displayed significantly increased ReHo in the left precuneus, and decreased ReHo in the right fusiform. The ReHo values in the left precuneus and the right fusiform had no significant correlation with the score of the depression rating scale or illness duration in both patient subgroups. Compared to young HC, patients with EOD showed significantly increased ReHo in the right frontoparietal regions and the right calcarine. Furthermore, the increased ReHo in the right frontoparietal regions, right insula and left hippocampus, and decreased ReHo in the left inferior occipital gyrus, right middle occipital gyrus, left calcarine, and left supplementary motor area were observed in patients with LOD when compared to old HC. The ReHo of brain areas that were related to mood regulation was changed in the first-episode, drug-naive adult patients with MDD. Adult patients with EOD and LOD exhibited different ReHo abnormalities relative to each age-matched comparison group, suggesting that depressed adult patients with different age-onset might have different pathological mechanism.

Clinical benefits of antimicrobial de-escalation in adults with community-onset monomicrobial Escherichia coli, Klebsiella species and Proteus mirabilis bacteremia.

PubMed

Lee, Ching-Chi; Wang, Jiun-Ling; Lee, Chung-Hsun; Hung, Yuan-Pin; Hong, Ming-Yuan; Tang, Hung-Jen; Ko, Wen-Chien

2017-09-01

The clinical benefits of an antimicrobial de-escalation strategy were compared with those of a no-switch strategy in bacteremic patients. Adults with community-onset monomicrobial Escherichia coli, Klebsiella species and Proteus mirabilis bacteremia treated empirically using broad-spectrum beta-lactams, including third-generation cephalosporins (GCs), fourth-GC or carbapenems, were treated definitively with first- or second-GCs (de-escalation group), the same regimens as empirical antibiotics (no-switch group), or antibiotics with a broader-spectrum than empirical antibiotics (escalation group). The eligible 454 adults were categorized as the de-escalation (231 patients, 50.9%), no-switch (177, 39.0%), and escalation (46, 10.1%) groups. Patients with de-escalation therapy were more often female, had less critical illness and fatal comorbidity, and had a higher survival rate than patients in the other two groups. After propensity score matching in the de-escalation and no-switch groups, critical illness at onset (Pitt bacteremia score ≥ 4; 16.5% vs. 12.7%; P = 0.34) or day 3 (2.5% vs. 2.5%; P = 1.00), fatal comorbidity (16.5% vs. 21.5%; P = 0.25), time to defervescence (4.6 vs. 4.7 days; P = 0.89), hospital stays (11.5 vs. 10.3 days; P = 0.13) and 4-week crude mortality rate (4.4% vs. 4.4%; P = 1.00) were similar. However, lower antibiotic cost (mean: 212.1 vs. 395.6 US$, P <0.001) and fewer complications of bloodstream infections due to resistant pathogens (0% vs. 5.1%, P = 0.004) were observed in the de-escalation group. De-escalation to narrower-spectrum cephalosporins is safe and cost-effective for adults with community-onset EKP bacteremia stabilized by empirical broad-spectrum beta-lactams. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Characteristics and outcomes of older adults with long-standing versus late-onset asthma.

PubMed

Herscher, Michael L; Wisnivesky, Juan P; Busse, Paula J; Hanania, Nicola A; Sheng, Tianyun; Wolf, Michael S; Federman, Alex D

2017-04-01

To examine the effect of age of onset on clinical characteristics and outcomes in a cohort of older patients with long-standing (LSA) and late-onset asthma (LOA). In all, 452 patients 60 years of age and older with persistent asthma were recruited. We defined LOA as asthma developing at age 40 or later and LSA as developing before age 40. We compared airway obstruction as assessed by spirometry, as well as asthma control using the Asthma Control Questionnaire (ACQ), quality of life using the Mini Asthma Quality of Life Questionnaire (AQLQ), and asthma-related emergency department visits and hospitalizations among patients with LSA vs. LOA. Patients with LOA, were less likely to have FEV 1 <70% of predicted (23% vs. 40%, p = 0.0002), to have FEV 1 /FVC<0.7 (27% vs. 38%, p = 0.01), or to have been intubated in the past (5% vs. 14%, p = 0.0007), and were also less likely to report a history of allergic conditions (64% vs 76%, p = 0.007). There was no significant difference in the level of asthma control, quality of life, or health care utilization. Older adults with LOA have different clinical and physiological characteristics and outcomes compared to those with LSA. Some of these differences may represent sequelae of longstanding disease, however LOA may also represent a different clinical phenotype that could influence management approaches.

Adult-onset hypogonadism: evaluation and role of testosterone replacement therapy.

PubMed

Davidiuk, Andrew J; Broderick, Gregory A

2016-12-01

Testosterone deficiency (TD) has become a growing concern in the field of men's sexual health, with an increasing number of men presenting for evaluation of this condition. Given the increasing demand for testosterone replacement therapy (TRT), a panel of experts met in August of 2015 to discuss the treatment of men who present for evaluation in the setting of low or normal gonadotropin levels and the associated signs and symptoms of hypogonadism. This constellation of factors can be associated with elements of both primary and secondary hypogonadism. Because this syndrome commonly occurs in men who are middle-aged and older, it was termed adult-onset hypogonadism (AOH). AOH can be defined by the following elements: low levels of testosterone, associated signs and symptoms of hypogonadism, and low or normal gonadotropin levels. Although there are significant benefits of TRT for patients with AOH, candidates also need to understand the potential risks. Patients undergoing TRT will need to be monitored regularly because there are potential complications that can develop with long-term use. This review is aimed at providing a deeper understanding of AOH, discussing the benefits and risks of TRT, and outlining each modality of TRT in use for AOH.

Age of onset and the subclassification of conduct/dissocial disorder

PubMed Central

Silberg, Judy; Moore, Ashlee A.; Rutter, Michael

2015-01-01

Background Conduct Disorder (CD) is a markedly heterogeneous psychiatric condition. Moffitt (1993) proposed that subclassification of CD should be according to age of onset. Our goals were to compare childhood-onset and adolescent-onset CD in terms of differences in phenotypic risk factors, genetic analyses, and factors associated with the persistence of antisocial behavior into young adulthood. Methods The data are from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) and Young Adult Follow-Up (YAFU). Childhood-onset CD was defined as CD beginning at or before age 11. Adolescent-onset CD was defined as having CD onset between ages 14 and 17. These subgroups were compared on ADHD, young adult antisocial behavior (ASB), family dysfunction, and parental depression. Genetic analyses compare childhood-onset and adolescent-onset CD, as well as their cooccurrence with ADHD and ASB. Finally, predictors of persistence were examined. Results Childhood-onset CD was significantly associated with ADHD, ASB, family dysfunction, and parental depression. Adolescent-onset CD was marginally associated with parental depression (p = .05) but not with any of the other risk factors. Univariate genetic models showed that both childhood-onset and adolescent-onset CD involve a large genetic liability accounting for 62% and 65% of the variance, respectively. A common genetic factor (as well as an ADHD-specific factor) accounted for the cooccurence of childhood-onset CD and ADHD. The cooccurrence of childhood-onset CD and ASB are reflected by a common genetic factor with genetic specific effects on ASB. There was no etiological link between adolescent-onset CD and either ADHD or ASB. Both ADHD and family dysfunction were significantly associated with the persistence of antisocial behavior into young adulthood. Conclusions Phenotypic findings differentiated between childhood-onset and adolescent-onset CD. ADHD and family dysfunction predicted persistence of antisocial

Age of onset and the subclassification of conduct/dissocial disorder.

PubMed

Silberg, Judy; Moore, Ashlee A; Rutter, Michael

2015-07-01

Conduct Disorder (CD) is a markedly heterogeneous psychiatric condition. Moffitt (1993) proposed that subclassification of CD should be according to age of onset. Our goals were to compare childhood-onset and adolescent-onset CD in terms of differences in phenotypic risk factors, genetic analyses, and factors associated with the persistence of antisocial behavior into young adulthood. The data are from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) and Young Adult Follow-Up (YAFU). Childhood-onset CD was defined as CD beginning at or before age 11. Adolescent-onset CD was defined as having CD onset between ages 14 and 17. These subgroups were compared on ADHD, young adult antisocial behavior (ASB), family dysfunction, and parental depression. Genetic analyses compare childhood-onset and adolescent-onset CD, as well as their cooccurrence with ADHD and ASB. Finally, predictors of persistence were examined. Childhood-onset CD was significantly associated with ADHD, ASB, family dysfunction, and parental depression. Adolescent-onset CD was marginally associated with parental depression (p = .05) but not with any of the other risk factors. Univariate genetic models showed that both childhood-onset and adolescent-onset CD involve a large genetic liability accounting for 62% and 65% of the variance, respectively. A common genetic factor (as well as an ADHD-specific factor) accounted for the cooccurrence of childhood-onset CD and ADHD. The cooccurrence of childhood-onset CD and ASB are reflected by a common genetic factor with genetic specific effects on ASB. There was no etiological link between adolescent-onset CD and either ADHD or ASB. Both ADHD and family dysfunction were significantly associated with the persistence of antisocial behavior into young adulthood. Phenotypic findings differentiated between childhood-onset and adolescent-onset CD. ADHD and family dysfunction predicted persistence of antisocial behavior into young adulthood. © 2014

Comparison of clinical and serological differences among juvenile-, adult-, and late-onset systemic lupus erythematosus in Korean patients.

PubMed

Choi, J H; Park, D J; Kang, J H; Yim, Y R; Lee, K E; Lee, J W; Wen, L; Kim, T J; Park, Y W; Lee, J K; Lee, S S

2015-10-01

We investigated whether systemic lupus erythematosus (SLE) patients could be distinguished based on the time of disease onset and, if so, whether the groups differed in their clinical and laboratory features in ethnically homogeneous Korean patients. We enrolled 201 SLE patients with available clinical data at the time of onset of SLE from the lupus cohort at Chonnam National University Hospital. Sociodemographic, clinical, and laboratory data, including autoantibodies, and concomitant diseases were found at the time of diagnosis of SLE by reviewing patient charts. We divided SLE patients according to age at SLE diagnosis into three groups: juvenile-onset SLE (JSLE, diagnosed at ≤ 18 years), adult-onset SLE (ASLE, diagnosed at 19-50 years), and late-onset SLE (LSLE, diagnosed at >50 years), and compared baseline demographic, clinical, and relevant laboratory findings. Of the 201 patients, 27 (14.4%), 149 (74.1%), and 25 (12.4%) were JSLE, ASLE, and LSLE patients, respectively. Fever, oral ulcers, nephritis, anemia, and thrombocytopenia were more common in JSLE patients than ASLE or LSLE patients (p < 0.05, < 0.05, 0.001, < 0.05, and < 0.05, respectively). However, Sjögren's syndrome was more frequent in LSLE patients than JSLE or ASLE patients (p < 0.05). Disease activity was significantly higher in JSLE patients than in ASLE or LSLE patients (p < 0.001). Anti-dsDNA and anti-nucleosome antibodies were found more frequently in JSLE patients and less frequently in LSLE patients (p < 0.05 and 0.005, respectively) and decreased complement levels were more common in JSLE patients and less common in LSLE patients (p < 0.001, 0.001, and < 0.05, respectively). Our results indicate that SLE patients present with different clinical and serological manifestations according to age at disease onset. JSLE patients have more severe disease activity and more frequent renal involvement and LSLE patients have milder disease activity, more

Typical versus delayed speech onset influences verbal reporting of autistic interests.

PubMed

Chiodo, Liliane; Majerus, Steve; Mottron, Laurent

2017-01-01

The distinction between autism and Asperger syndrome has been abandoned in the DSM-5. However, this clinical categorization largely overlaps with the presence or absence of a speech onset delay which is associated with clinical, cognitive, and neural differences. It is unknown whether these different speech development pathways and associated cognitive differences are involved in the heterogeneity of the restricted interests that characterize autistic adults. This study tested the hypothesis that speech onset delay, or conversely, early mastery of speech, orients the nature and verbal reporting of adult autistic interests. The occurrence of a priori defined descriptors for perceptual and thematic dimensions were determined, as well as the perceived function and benefits, in the response of autistic people to a semi-structured interview on their intense interests. The number of words, grammatical categories, and proportion of perceptual / thematic descriptors were computed and compared between groups by variance analyses. The participants comprised 40 autistic adults grouped according to the presence ( N  = 20) or absence ( N  = 20) of speech onset delay, as well as 20 non-autistic adults, also with intense interests, matched for non-verbal intelligence using Raven's Progressive Matrices. The overall nature, function, and benefit of intense interests were similar across autistic subgroups, and between autistic and non-autistic groups. However, autistic participants with a history of speech onset delay used more perceptual than thematic descriptors when talking about their interests, whereas the opposite was true for autistic individuals without speech onset delay. This finding remained significant after controlling for linguistic differences observed between the two groups. Verbal reporting, but not the nature or positive function, of intense interests differed between adult autistic individuals depending on their speech acquisition history: oral reporting of

Predictive genetic testing for adult-onset disorders in minors: a critical analysis of the arguments for and against the 2013 ACMG guidelines.

PubMed

Anderson, J A; Hayeems, R Z; Shuman, C; Szego, M J; Monfared, N; Bowdin, S; Zlotnik Shaul, R; Meyn, M S

2015-04-01

The publication of the ACMG recommendations has reignited the debate over predictive testing for adult-onset disorders in minors. Response has been polarized. With this in mind, we review and critically analyze this debate. First, we identify long-standing inconsistencies between consensus guidelines and clinical practice regarding risk assessment for adult-onset genetic disorders in children using family history and molecular analysis. Second, we discuss the disparate assumptions regarding the nature of whole genome and exome sequencing underlying arguments of both supporters and critics, and the role these assumptions play in the arguments for and against reporting. Third, we suggest that implicit differences regarding the definition of best interests of the child underlie disparate conclusions as to the best interests of children in this context. We conclude by calling for clarity and consensus concerning the central foci of this debate. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Abnormal functional brain connectivity and personality traits in myotonic dystrophy type 1.

PubMed

Serra, Laura; Silvestri, Gabriella; Petrucci, Antonio; Basile, Barbara; Masciullo, Marcella; Makovac, Elena; Torso, Mario; Spanò, Barbara; Mastropasqua, Chiara; Harrison, Neil A; Bianchi, Maria L E; Giacanelli, Manlio; Caltagirone, Carlo; Cercignani, Mara; Bozzali, Marco

2014-05-01

Myotonic dystrophy type 1 (DM1), the most common muscular dystrophy observed in adults, is a genetic multisystem disorder affecting several other organs besides skeletal muscle, including the brain. Cognitive and personality abnormalities have been reported; however, no studies have investigated brain functional networks and their relationship with personality traits/disorders in patients with DM1. To use resting-state functional magnetic resonance imaging to assess the potential relationship between personality traits/disorders and changes to functional connectivity within the default mode network (DMN) in patients with DM1. We enrolled 27 patients with genetically confirmed DM1 and 16 matched healthy control individuals. Patients underwent personality assessment using clinical interview and Minnesota Multiphasic Personality Inventory-2 administration; all participants underwent resting-state functional magnetic resonance imaging. Investigations were conducted at the Istituto di Ricovero e Cura a Carattere Scientifico Santa Lucia Foundation, Catholic University of Sacred Heart, and Azienda Ospedaliera San Camillo Forlanini. Resting-state functional magnetic resonance imaging. Measures of personality traits in patients and changes in functional connectivity within the DMN in patients and controls. Changes in functional connectivity and atypical personality traits in patients were correlated. We combined results obtained from the Minnesota Multiphasic Personality Inventory-2 and clinical interview to identify a continuum of atypical personality profiles ranging from schizotypal personality traits to paranoid personality disorder within our DM1 patients. We also demonstrated an increase in functional connectivity in the bilateral posterior cingulate and left parietal DMN nodes in DM1 patients compared with controls. Moreover, patients with DM1 showed strong associations between DMN functional connectivity and schizotypal-paranoid traits. Our findings provide novel

[Dystrophia myotonica (Steinert disease)--a frequently misdiagnosed disease].

PubMed

Kuhn, E; Lehmann-Horn, F; Rüdel, R

1990-06-01

Dystrophia myotonica (Steinert's disease) is the most common hereditary disease of the neuromuscular system in adults. Its mode of inheritance is autosomal dominant. The gene responsible for its is located on chromosome 19 in the linkage domain of the loci for the apolipoproteins C2, C1 und E and of the creatine kinase of skeletal muscle (CKMM). Myotonic dystrophy is categorized in an adult and in a congenital form. In the adult form, the characteristic findings are muscular atrophy in certain regions of the body (face, neck and distally in the extremities) and myotonia. Cataract, intraocular hypotension, gonadal atrophy, conduction abnormalities in the heart and hearing deficiencies appear quite often in the course of the disease. In the congenital form, general muscle weekness (particularly pronounced in the face) is the leading finding, combined with retarded loco motor and mental development. A decisive criterion for the diagnosis of this form is the occurrence of myotonic dystrophy in the patient's mother. Electromyographic investigation is indicated when a suspicion of myotonic dystrophy cannot be ascertained on the basis of clinical and genetic findings. Myotonic runs in the EMG will then corroborate the suspicion. Recent electrophysiological investigations have indicated that at least three different types of channels for the passage of ions through the membrane of the skeletal muscle cells show abnormal behaviour, i.e. the channel for Cl-, Na+ and K+. These findings corroborate the hypothesis that the abnormality responsible for myotonic dystrophy is situated in the membrane systems. A pharmacological treatment of the muscular dystrophy has not yet been developed.(ABSTRACT TRUNCATED AT 250 WORDS)

Genes and Pathways Involved in Adult Onset Disorders Featuring Muscle Mitochondrial DNA Instability

PubMed Central

Ahmed, Naghia; Ronchi, Dario; Comi, Giacomo Pietro

2015-01-01

Replication and maintenance of mtDNA entirely relies on a set of proteins encoded by the nuclear genome, which include members of the core replicative machinery, proteins involved in the homeostasis of mitochondrial dNTPs pools or deputed to the control of mitochondrial dynamics and morphology. Mutations in their coding genes have been observed in familial and sporadic forms of pediatric and adult-onset clinical phenotypes featuring mtDNA instability. The list of defects involved in these disorders has recently expanded, including mutations in the exo-/endo-nuclease flap-processing proteins MGME1 and DNA2, supporting the notion that an enzymatic DNA repair system actively takes place in mitochondria. The results obtained in the last few years acknowledge the contribution of next-generation sequencing methods in the identification of new disease loci in small groups of patients and even single probands. Although heterogeneous, these genes can be conveniently classified according to the pathway to which they belong. The definition of the molecular and biochemical features of these pathways might be helpful for fundamental knowledge of these disorders, to accelerate genetic diagnosis of patients and the development of rational therapies. In this review, we discuss the molecular findings disclosed in adult patients with muscle pathology hallmarked by mtDNA instability. PMID:26251896

Quantitative Methods to Monitor RNA Biomarkers in Myotonic Dystrophy.

PubMed

Wojciechowska, Marzena; Sobczak, Krzysztof; Kozlowski, Piotr; Sedehizadeh, Saam; Wojtkowiak-Szlachcic, Agnieszka; Czubak, Karol; Markus, Robert; Lusakowska, Anna; Kaminska, Anna; Brook, J David

2018-04-12

Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are human neuromuscular disorders associated with mutations of simple repetitive sequences in affected genes. The abnormal expansion of CTG repeats in the 3'-UTR of the DMPK gene elicits DM1, whereas elongated CCTG repeats in intron 1 of ZNF9/CNBP triggers DM2. Pathogenesis of both disorders is manifested by nuclear retention of expanded repeat-containing RNAs and aberrant alternative splicing. The precise determination of absolute numbers of mutant RNA molecules is important for a better understanding of disease complexity and for accurate evaluation of the efficacy of therapeutic drugs. We present two quantitative methods, Multiplex Ligation-Dependent Probe Amplification and droplet digital PCR, for studying the mutant DMPK transcript (DMPK exp RNA) and the aberrant alternative splicing in DM1 and DM2 human tissues and cells. We demonstrate that in DM1, the DMPK exp RNA is detected in higher copy number than its normal counterpart. Moreover, the absolute number of the mutant transcript indicates its low abundance with only a few copies per cell in DM1 fibroblasts. Most importantly, in conjunction with fluorescence in-situ hybridization experiments, our results suggest that in DM1 fibroblasts, the vast majority of nuclear RNA foci consist of a few molecules of DMPK exp RNA.

Prevalence of Pathogenic Copy Number Variation in Adults With Pediatric-Onset Epilepsy and Intellectual Disability.

PubMed

Borlot, Felippe; Regan, Brigid M; Bassett, Anne S; Stavropoulos, D James; Andrade, Danielle M

2017-11-01

Copy number variation (CNV) is an important cause of neuropsychiatric disorders. Little is known about the role of CNV in adults with epilepsy and intellectual disability. To evaluate the prevalence of pathogenic CNVs and identify possible candidate CNVs and genes in patients with epilepsy and intellectual disability. In this cross-sectional study, genome-wide microarray was used to evaluate a cohort of 143 adults with unexplained childhood-onset epilepsy and intellectual disability who were recruited from the Toronto Western Hospital epilepsy outpatient clinic from January 1, 2012, through December 31, 2014. The inclusion criteria were (1) pediatric seizure onset with ongoing seizure activity in adulthood, (2) intellectual disability of any degree, and (3) no structural brain abnormalities or metabolic conditions that could explain the seizures. DNA screening was performed using genome-wide microarray platforms. Pathogenicity of CNVs was assessed based on the American College of Medical Genetics guidelines. The Residual Variation Intolerance Score was used to evaluate genes within the identified CNVs that could play a role in each patient's phenotype. Of the 2335 patients, 143 probands were investigated (mean [SD] age, 24.6 [10.8] years; 69 male and 74 female). Twenty-three probands (16.1%) and 4 affected relatives (2.8%) (mean [SD] age, 24.1 [6.1] years; 11 male and 16 female) presented with pathogenic or likely pathogenic CNVs (0.08-18.9 Mb). Five of the 23 probands with positive results (21.7%) had more than 1 CNV reported. Parental testing revealed de novo CNVs in 11 (47.8%), with CNVs inherited from a parent in 4 probands (17.4%). Sixteen of 23 probands (69.6%) presented with previously cataloged human genetic disorders and/or defined CNV hot spots in epilepsy. Eight nonrecurrent rare CNVs that overlapped 1 or more genes associated with intellectual disability, autism, and/or epilepsy were identified: 2p16.1-p15 duplication, 6p25.3-p25.1 duplication, 8p23.3p

Sex, stressful life events, and adult onset depression and alcohol dependence: are men and women equally vulnerable?

PubMed

Slopen, Natalie; Williams, David R; Fitzmaurice, Garrett M; Gilman, Stephen E

2011-08-01

Higher rates of major depression (MD) among females, and of alcohol dependence (AD) among males, are among the most routinely reported findings in psychiatric epidemiology. One of the most often pursued explanations for sex differences in both disorders suggests that males and females have a differential vulnerability to stressors, which is manifested in sex-specific ways (MD for females, AD for males). However, existing evidence in support of this explanation is mixed. In the present study, we investigated sex differences in the association between stressful life events and MD and AD in a large national sample of adults in the United States (n = 32,744) using a prospective design. Logistic regression was used to estimate associations between stressful life events and both MD and AD; sex-specific effects of stress on MD and AD were evaluated by testing interaction terms between sex and stressors in the prediction of both outcomes. The number of stressful life events was predictive of first onset MD and AD. This was true for both males and females, and sex-by-stress interaction terms did not support the hypothesis that sex-specific responses to stressful life events lead to sex differences in first onset of MD and AD among adults. These results indicate the resistance of sex differences in MD and AD to simple explanations, and suggest the need for more nuanced models that incorporate both physiological and social aspects of vulnerability. Copyright © 2011 Elsevier Ltd. All rights reserved.

Indoor dampness and molds and development of adult-onset asthma: a population-based incident case-control study.

PubMed Central

Jaakkola, Maritta S; Nordman, Henrik; Piipari, Ritva; Uitti, Jukka; Laitinen, Jukka; Karjalainen, Antti; Hahtola, Paula; Jaakkola, Jouni J K

2002-01-01

Previous cross-sectional and prevalent case-control studies have suggested increased risk of asthma in adults related to dampness problems and molds in homes. We conducted a population-based incident case-control study to assess the effects of indoor dampness problems and molds at work and at home on development of asthma in adults. We recruited systematically all new cases of asthma during a 2.5-year study period (1997-2000) and randomly selected controls from a source population consisting of adults 21-63 years old living in the Pirkanmaa Hospital district, South Finland. The clinically diagnosed case series consisted of 521 adults with newly diagnosed asthma and the control series of 932 controls, after we excluded 76 (7.5%) controls with a history of asthma. In logistic regression analysis adjusting for confounders, the risk of asthma was related to the presence of visible mold and/or mold odor in the workplace (odds ratio, 1.54; 95% confidence interval, 1.01-2.32) but not to water damage or damp stains alone. We estimated the fraction of asthma attributable to workplace mold exposure to be 35.1% (95% confidence interval, 1.0-56.9%) among the exposed. Present results provide new evidence of the relation between workplace exposure to indoor molds and adult-onset asthma. PMID:12003761

Temperament and character in patients with classical myotonic dystrophy type 1 (DM-1).

PubMed

Winblad, S; Lindberg, C; Hansen, S

2005-04-01

This study was designed to investigate personality in classical Myotonic Dystrophy (DM-1). Forty-six patients with DM-1 (25 women and 21 men), 31 healthy controls and 37 subjects in a contrast group, consisting of patients with other muscle disorders (spinal muscular atrophy, facioscapulohumeral dystrophy and limb girdle muscular dystrophy), completed the Temperament and Character Inventory (TCI) (Cloninger, 1994). We aimed to establish whether CTG triplet repeat size correlated with ratings of personality dimensions in the TCI. The DM-1 patients scored significantly higher on the TCI dimension Harm avoidance and lower on Persistence, Self-directedness and Cooperativeness. Signs of a personality disorder were found in 20% of the DM-1 patients. No correlation was found between the number of CTG repeats and scores in the TCI. This study indicates deviant personality in classical DM-1 regarding temperament and character, both in comparison to healthy controls and to patients with other muscle disorders with no known brain disorder.

Relationship between acoustic voice onset and offset and selected instances of oscillatory onset and offset in young healthy males and females

PubMed Central

Patel, Rita; Forrest, Karen; Hedges, Drew

2016-01-01

Objective To investigate the relationship between (1) onset of the acoustic signal and pre-phonatory phases associated with oscillatory onset and (2) offset of the acoustic signal with the post-phonatory events associated with oscillatory offset across vocally healthy adults. Subjects and Methods High-speed videoendoscopy was captured simultaneously with the acoustic signal during repeated production of /hi.hi.hi/ at typical pitch and loudness from 56 vocally healthy adults (age 20–42 years; 21 male, 35 female). The relationship between the acoustic sound pressure signal and oscillatory onset /offset events from the glottal area waveforms (GAW), were statistically investigated using a multivariate linear regression analysis. Results The onset of the acoustic signal (X1a) is a significant predictor of the onset of first oscillations (X1g) and onset of sustained oscillations (X2g). X1a as well as gender are significant predictors of the first instance of medial contact (X1.5g). The offset of the acoustic signal (X2a) is a significant predictor of the first instance of oscillatory offset (X3g), first instance of incomplete glottal closure (X3.5g), and cessation of vocal fold motion (X4g). Conclusions The acoustic signal onset is closely related to the first medial contact of the vocal folds but the latency between these events is longer for females compared to males. The offset of the acoustic signal occurs immediately after incomplete glottal adduction. The emerging normative group latencies between the onset/offset of the acoustic and the GAW from this study appear promising for future investigations. PMID:27769696

Age of onset of recurrent respiratory papillomatosis: a distribution analysis.

PubMed

San Giorgi, M R M; van den Heuvel, E R; Tjon Pian Gi, R E A; Brunings, J W; Chirila, M; Friedrich, G; Golusinski, W; Graupp, M; Horcasitas Pous, R A; Ilmarinen, T; Jackowska, J; Koelmel, J C; Ferran Vilà, F; Weichbold, V; Wierzbicka, M; Dikkers, F G

2016-10-01

Distribution of age of onset of recurrent respiratory papillomatosis (RRP) is generally described to be bimodal, with peaks at approximately 5 years and 30 years. This assumption has never been scientifically confirmed, and authors tend to refer to an article that does not describe distribution. Knowledge of the distribution of age of onset is important for virological and epidemiological comprehension. The objective of this study was to determine the distribution of age of onset of RRP in a large international sample. Cross-sectional distribution analysis. Laryngologists from 12 European hospitals provided information on date of birth and date of onset of all their RRP patients treated between 1998 and 2012. Centers that exclusively treated either patients with juvenile onset RRP or patients with adult onset RRP, or were less accessible for one of these groups, were excluded to prevent skewness. A mixture model was implemented to describe distribution of age of onset. The best fitting model was selected using the Bayesian information criterion. Six hundred and thirty-nine patients were included in the analysis. Age of onset was described by a three component mixture distribution with lognormally distributed components. Recurrent respiratory papillomatosis starts at three median ages 7, 35 and 64 years. Distribution of age of onset of RRP shows three peaks. In addition to the already adopted idea of age peaks at paediatric and adult age, there is an additional peak around the age of 64. © 2015 John Wiley & Sons Ltd.

Influence of the sex of the transmitting grandparent in congenital myotonic dystrophy.

PubMed

López de Munain, A; Cobo, A M; Poza, J J; Navarrete, D; Martorell, L; Palau, F; Emparanza, J I; Baiget, M

1995-09-01

To analyse the influence of the sex of the transmitting grandparents on the occurrence of the congenital form of myotonic dystrophy (CDM), we have studied complete three generation pedigrees of 49 CDM cases, analysing: (1) the sex distribution in the grandparents' generation, and (2) the intergenerational amplification of the CTG repeat, measured in its absolute and relative values, between grandparents and the mothers of CDM patients and between the latter and their CDM children. The mean relative intergenerational increase in the 32 grandparent-mother pairs was significantly greater than in the 56 mother-CDM pairs (Mann-Whitney U test, p < 0.001). The mean expansion of the grandfathers (103 CTG repeats) was also significantly different from that seen in the grandmothers' group (154 CTG repeats) (Mann-Whitney U test, p < 0.01). This excess of non-manifesting males between the CDM grandparents' generation with a smaller CTG length than the grandmothers could suggest that the premutation has to be transmitted by a male to reach the degree of instability responsible for subsequent intergenerational CTG expansions without size constraints characteristic of the CDM range.

Valerenic acid and Valeriana officinalis extracts delay onset of Pentylenetetrazole (PTZ)-Induced seizures in adult Danio rerio (Zebrafish).

PubMed

Torres-Hernández, Bianca A; Del Valle-Mojica, Lisa M; Ortíz, José G

2015-07-14

Anticonvulsant properties have been attributed to extracts of the herbal medicine Valeriana officinalis. Our aims were to examine the anticonvulsant properties of valerenic acid and valerian extracts and to determine whether valerian preparations interact with the activity of other anti-epileptic drugs (phenytoin or clonazepam). To achieve these goals, we validated the adult zebrafish, Danio rerio, as an animal model for studying anticonvulsant drugs. All drug treatments were administered by immersion in water containing the drug. For assays of anticonvulsant activity, zebrafish were pretreated with: anti-epileptic drugs, valerenic acid, aqueous or ethanolic valerian extracts, or mixtures (phenytoin or clonazepam with valerenic acid or valerian extracts). Seizures were then induced with pentylenetetrazole (PTZ). A behavioral scale was developed for scoring PTZ-induced seizures in adult zebrafish. The seizure latency was evaluated for all pretreatments and control, untreated fish. Valerenic acid and both aqueous and ethanolic extracts of valerian root were also evaluated for their ability to improve survival after pentylenetetrazole-challenge. The assay was validated by comparison with well-studied anticonvulsant drugs (phenytoin, clonazepam, gabapentin and valproate). One-way ANOVA followed by Tukey post-hoc test was performed, using a p < 0.05 level of significance. All treatments were compared with the untreated animals and with the other pretreatments. After exposure to pentylenetetrazole, zebrafish exhibited a series of stereotypical behaviors prior to the appearance of clonic-like movements--convulsions. Both valerenic acid and valerian extracts (aqueous and ethanolic) significantly extended the latency period to the onset of seizure (convulsion) in adult zebrafish. The ethanolic valerian extract was a more potent anticonvulsant than the aqueous extract. Valerenic acid and both valerian extracts interacted synergistically with clonazepam to extended the

Comparison on radiographic progression for 5 years between juvenile onset ankylosing spondylitis and adult onset ankylosing spondylitis: an observational study of the Korean SpondyloArthropathy Registry (OSKAR) data.

PubMed

Kim, Tae-Jong; Shin, Ji-Hui; Sung, Il-Hoon; Lee, Seunghun; Song, Yoonah; Kim, Tae-Hwan

2016-01-01

To evaluate differences in radiographic progression between adult-onset ankylosing spondylitis (AoAS) and juvenile-onset ankylosing spondylitis (JoAS). A total of 533 patients (418 patients with AoAS and 115 patients with JoAS) from the Observation Study of Korean spondyloArthropathy Registry (OSKAR) cohort were enrolled. All baseline OSKAR data were analysed in relation to disease onset and radiographic progression was analysed between the groups over 5 years. The modified Stoke AS Spinal Score (mSASSS) were used by two experienced radiologists. Clinical data were collected to investigate the associations between clinical factors and radiographic progression. Radiographic scores were compared using analysis of covariance model after adjusting for confounding factors. Inter-reader reliability for baseline mSASSS was very good. Inter-reader reliability for the changes in the mSASSS was also good. A significant difference in baseline mSASSS (mean ± SD) unit was detected between the AoAS and JoAS groups (18.1±17.4 vs. 14.3±13.8, p=0.015). We assessed the change in mSASSS to confirm whether age at onset affected radiographic progression. A simple comparison revealed a significant difference between changes on the mSASSS (mean ± SEM) between the JoAS and AoAS groups (1.75±0.71 vs. 3.77±0.56, p<0.001). After adjusting for multiple comparisons, change on the mSASSS remained lower in patients with JoAS than those with AoAS (0.28±1.33 vs. 4.08±0.62, p=0.016). Patients with JoAS had slower radiographic spinal damage progression over 5 years than those with AoAS.

Objective measures of sleep and dim light melatonin onset in adolescents and young adults with delayed sleep phase disorder compared to healthy controls.

PubMed

Saxvig, Ingvild W; Wilhelmsen-Langeland, Ane; Pallesen, Ståle; Vedaa, Oystein; Nordhus, Inger H; Sørensen, Eli; Bjorvatn, Bjørn

2013-08-01

Delayed sleep phase disorder is characterized by a delay in the timing of the major sleep period relative to conventional norms. The sleep period itself has traditionally been described as normal. Nevertheless, it is possible that sleep regulatory mechanism disturbances associated with the disorder may affect sleep duration and/or architecture. Polysomnographic data that may shed light on the issue are scarce. Hence, the aim of this study was to examine polysomnographic measures of sleep in adolescents and young adults with delayed sleep phase disorder, and to compare findings to that of healthy controls. A second aim was to estimate dim light melatonin onset as a marker of circadian rhythm and to investigate the phase angle relationship (time interval) between dim light melatonin onset and the sleep period. Data from 54 adolescents and young adults were analysed, 35 diagnosed with delayed sleep phase disorder and 19 healthy controls. Results show delayed timing of sleep in participants with delayed sleep phase disorder, but once sleep was initiated no group differences in sleep parameters were observed. Dim light melatonin onset was delayed in participants with delayed sleep phase disorder, but no difference in phase angle was observed between the groups. In conclusion, both sleep and dim light melatonin onset were delayed in participants with delayed sleep phase disorder. The sleep period appeared to occur at the same circadian phase in both groups, and once sleep was initiated no differences in sleep parameters were observed. © 2013 European Sleep Research Society.

Adult-Onset Hypothyroidism Enhances Fear Memory and Upregulates Mineralocorticoid and Glucocorticoid Receptors in the Amygdala

PubMed Central

Montero-Pedrazuela, Ana; Fernández-Lamo, Iván; Alieva, María; Pereda-Pérez, Inmaculada; Venero, César; Guadaño-Ferraz, Ana

2011-01-01

Hypothyroidism is the most common hormonal disease in adults, which is frequently accompanied by learning and memory impairments and emotional disorders. However, the deleterious effects of thyroid hormones deficiency on emotional memory are poorly understood and often underestimated. To evaluate the consequences of hypothyroidism on emotional learning and memory, we have performed a classical Pavlovian fear conditioning paradigm in euthyroid and adult-thyroidectomized Wistar rats. In this experimental model, learning acquisition was not impaired, fear memory was enhanced, memory extinction was delayed and spontaneous recovery of fear memory was exacerbated in hypothyroid rats. The potentiation of emotional memory under hypothyroidism was associated with an increase of corticosterone release after fear conditioning and with higher expression of glucocorticoid and mineralocorticoid receptors in the lateral and basolateral nuclei of the amygdala, nuclei that are critically involved in the circuitry of fear memory. Our results demonstrate for the first time that adult-onset hypothyroidism potentiates fear memory and also increases vulnerability to develop emotional memories. Furthermore, our findings suggest that enhanced corticosterone signaling in the amygdala is involved in the pathophysiological mechanisms of fear memory potentiation. Therefore, we recommend evaluating whether inappropriate regulation of fear in patients with post-traumatic stress and other mental disorders is associated with abnormal levels of thyroid hormones, especially those patients refractory to treatment. PMID:22039511

Adult-onset hypothyroidism enhances fear memory and upregulates mineralocorticoid and glucocorticoid receptors in the amygdala.

PubMed

Montero-Pedrazuela, Ana; Fernández-Lamo, Iván; Alieva, María; Pereda-Pérez, Inmaculada; Venero, César; Guadaño-Ferraz, Ana

2011-01-01

Hypothyroidism is the most common hormonal disease in adults, which is frequently accompanied by learning and memory impairments and emotional disorders. However, the deleterious effects of thyroid hormones deficiency on emotional memory are poorly understood and often underestimated. To evaluate the consequences of hypothyroidism on emotional learning and memory, we have performed a classical Pavlovian fear conditioning paradigm in euthyroid and adult-thyroidectomized Wistar rats. In this experimental model, learning acquisition was not impaired, fear memory was enhanced, memory extinction was delayed and spontaneous recovery of fear memory was exacerbated in hypothyroid rats. The potentiation of emotional memory under hypothyroidism was associated with an increase of corticosterone release after fear conditioning and with higher expression of glucocorticoid and mineralocorticoid receptors in the lateral and basolateral nuclei of the amygdala, nuclei that are critically involved in the circuitry of fear memory. Our results demonstrate for the first time that adult-onset hypothyroidism potentiates fear memory and also increases vulnerability to develop emotional memories. Furthermore, our findings suggest that enhanced corticosterone signaling in the amygdala is involved in the pathophysiological mechanisms of fear memory potentiation. Therefore, we recommend evaluating whether inappropriate regulation of fear in patients with post-traumatic stress and other mental disorders is associated with abnormal levels of thyroid hormones, especially those patients refractory to treatment.

Genetic and neurophysiological correlates of the age of onset of alcohol use disorders in adolescents and young adults

PubMed Central

Chorlian, David B.; Rangaswamy, Madhavi; Manz, Niklas; Wang, Jen-Chyong; Dick, Danielle; Almasy, Laura; Bauer, Lance; Bucholz, Kathleen; Foroud, Tatiana; Hesselbrock, Victor; Kang, Sun J.; Kramer, John; Kuperman, Sam; Nurnberger, John; Rice, John; Schuckit, Marc; Tischfield, Jay; Edenberg, Howard J.; Goate, Alison; Bierut, Laura; Porjesz, Bernice

2013-01-01

Discrete time survival analysis (DTSA) was used to assess the age-specific association of event related oscillations (EROs) and CHRM2 gene variants on the onset of regular alcohol use and alcohol dependence. The subjects were 2938 adolescents and young adults ages 12 to 25. Results showed that the CHRM2 gene variants and ERO risk factors had hazards which varied considerably with age. The bulk of the significant age-specific associations occurred in those whose age of onset was under 16. These associations were concentrated in those subjects who at some time took an illicit drug. These results are consistent with studies which associate greater rates of alcohol dependence among those who begin drinking at an early age. The age specificity of the genetic and neurophysiological factors is consistent with recent studies of adolescent brain development, which locate an interval of heightened vulnerability to substance use disorders in the early to mid teens. PMID:23963516

Contextual risks linking parents’ adolescent marijuana use to offspring onset

PubMed Central

Kerr, David C. R.; Tiberio, Stacey S.; Capaldi, Deborah M.

2015-01-01

Objective We studied the extent to which parent marijuana use in adolescence is associated with marijuana use onset in offspring through contextual family and peer risks. Method Fathers assessed (n = 93) since childhood, their 146 offspring (n = 83 girls), and offspring's mothers (n = 85) participated in a longitudinal study. Using discrete-time survival analysis, fathers’ (prospectively measured) and mothers’ (retrospective) adolescent marijuana use was used to predict offspring marijuana use onset through age 19 years. Parental monitoring, child exposure to marijuana use, peer deviance, peer marijuana use, and perceptions of parent disapproval of child use were measured before or concurrent with onset. Results Parents’ adolescent marijuana use was significantly associated with less monitoring, offspring alcohol use, the peer behaviors, exposure to adult marijuana use, and perceptions of less parent disapproval. Male gender and the two peer behaviors were positively associated with children's marijuana use onset, controlling for their alcohol use. Parents’ adolescent marijuana use had a significant indirect effect on child onset through children's deviant peer affiliations and a composite contextual risk score. Conclusions Parents’ histories of marijuana use may contribute indirectly to children's marijuana use onset through their influence on the social environments children encounter; specifically, those characterized by more liberal use norms, exposure to marijuana use and deviant and marijuana-using peers, and less adult supervision. Given that alcohol use onset was controlled, findings suggest that the contextual factors identified here confer unique risk for child marijuana use onset. PMID:26166667

Prevalence and correlates of apathy in myotonic dystrophy type 1.

PubMed

Gallais, Benjamin; Montreuil, Michèle; Gargiulo, Marcela; Eymard, Bruno; Gagnon, Cynthia; Laberge, Luc

2015-08-22

Apathy in DM1 has long been acknowledged in clinical practice. However, a major drawback is that the concept has been only sparsely explored in previous specific studies. This study aimed to determine the prevalence of apathy in myotonic dystrophy (DM1), to compare it with facioscapulohumeral dystrophy (FSHD) patients and normal healthy controls, and explore its relationship to psychopathological features and cognitive function. Levels of apathy in 38 DM1 patients with adult phenotypes were compared with 19 patients with FSHD and 20 matched controls. Patient participants were consecutively recruited, regarding their interdisciplinary annual evaluation at the neuromuscular pathology reference center (Institute of Myology, Paris, France), within an 18-month period. Additional measurements included motor disability, fatigue, depression, anxiety, and cognitive abilities. Inter-group comparisons were performed using non-parametric Kruskal-Wallis tests and Mann-Whitney U Tests. Intra-group comparisons were carried out with the Wilcoxon Signed rank and Friedman tests. Also, Spearman's correlations were used to assess the strength of linear relationships between pairs of variables. The significance level was set at 0.05. Global score of apathy was significantly higher in DM1 patients than in FSHD patients (p < 0.01) and in controls (p < 0.001). Sixteen of 38 DM1 patients (39.5 %) met the criterion for apathy, contrasting with only 4 of the 19 (21.1 %) FSHD patients. No control subject was apathetic. Moreover, apathy in DM1 patients was negatively correlated to MMSE (r = -.46, p < .05) and Stroop Word (r = -.55, p < .01) scores, but not with age, educational level, disease duration, CTG repeats, motor functional disability, fatigue, depression, and anxiety. Apathy is a frequent symptom in DM1 (almost 40 %). It is more prevalent than in a similarly disabled group of patients with FSHD and in controls. Results also show that apathy in DM1 is

Antibodies in juvenile-onset myositis.

PubMed

Tansley, Sarah L

2016-11-01

Juvenile-onset myositis is a highly heterogeneous disease. Myositis-specific and associated autoantibodies provide a potential means of subdividing patients into clinically homogenous subgroups. Given the increasing availability of autoantibody testing, this review explores the phenotypes associated with different autoantibodies in juvenile-onset myositis and the potential clinical utility of autoantibody testing. Autoantibodies can be identified in 60-70% of children with myositis and the recent discovery of novel myositis-associated autoantibodies in adult patients suggests this may increase in the near future. Detailed phenotype descriptions are now known for several autoantibodies commonly identified in juvenile-onset disease. Whilst there is insufficient evidence to recommend a differential treatment approach based on autoantibody status, it is becoming increasingly clear that some autoantibody subgroups are often treatment resistant and may benefit from a more aggressive approach. The validation of nonspecialised methods for myositis-specific autoantibody detection should lead to more widely available testing. In juvenile-onset disease, this will provide detailed prognostic information and in the future may also influence approach.

Orthopaedic Disorders in Myotonic Dystrophy Type 1: descriptive clinical study of 21 patients

PubMed Central

2013-01-01

Background Myotonic Dystrophy Type 1 (DM1) is the most common form of hereditary myopathy presenting in adults. This autosomal-dominant systemic disorder is caused by a CTG repeat, demonstrating various symptoms. A mild, classic and congenital form can be distinguished. Often the quality of life is reduced by orthopaedic problems, such as muscle weakness, contractures, foot or spinal deformities, which limit patients’ mobility. The aim of our study was to gather information about the orthopaedic impairments in patients with DM1 in order to improve the medical care of patients, affected by this rare disease. Methods A retrospective clinical study was carried out including 21 patients (11 male and 10 female), all diagnosed with DM1 by genetic testing. All patients were seen during our special consultations for neuromuscular diseases, during which patients were interviewed and examined. We also reviewed surgery reports of our hospitalized patients. Results We observed several orthopaedic impairments: spinal deformities (scoliosis, hyperkyphosis, rigid spine), contractures (of the upper extremities and the lower extremities), foot deformities (equinus deformity, club foot, pes cavus, pes planovalgus, pes cavovarus, claw toes) and fractures. Five patients were affected by pulmonary diseases (obstructive airway diseases, restrictive lung dysfunctions). Twelve patients were affected by cardiac disorders (congenital heart defects, valvular heart defects, conduction disturbances, pulmonary hypertension, cardiomyopathy). Our patients received conservative therapy (physiotherapy, logopaedic therapy, ergotherapy) and we prescribed orthopaedic technical devices (orthopaedic custom-made shoes, insoles, lower and upper leg orthoses, wheelchair, Rehab Buggy). We performed surgery for spinal and foot deformities: the scoliosis of one patient was stabilized and seven patients underwent surgery for correction of foot deformities. Conclusions An orthopaedic involvement in DM1

Relationship Between Acoustic Voice Onset and Offset and Selected Instances of Oscillatory Onset and Offset in Young Healthy Men and Women.

PubMed

Patel, Rita R; Forrest, Karen; Hedges, Drew

2017-05-01

This study aimed to investigate the relationship between (1) onset of the acoustic signal (X 1 a ) and prephonatory phases associated with oscillatory onset and (2) offset of the acoustic signal (X 2 a ) with the postphonatory events associated with oscillatory offset across vocally healthy adults. High-speed videoendoscopy was captured simultaneously with the acoustic signal during repeated production of /hi.hi.hi/ at typical pitch and loudness from 56 vocally healthy adults (aged 20-42 years; 21 men, 35 women). The relationships between the acoustic sound pressure signal and oscillatory onset and offset events from the glottal area waveforms (GAWs) were statistically investigated using a multivariate linear regression analysis. The X 1 a is a significant predictor of the onset of first oscillatory motion (X 1 g ) and onset of sustained oscillations (X 2 g ). X 1 a as well as gender are significant predictors of the first medial contact of the vocal folds (X 1.5 g ). The X 2 a is a significant predictor of the first instance of oscillatory offset (X 3 g ), first instance of incomplete glottal closure (X 3.5 g ), and complete cessation of (vocal fold) oscillatory motion (X 4 g ). The acoustic signal onset is closely related to the X 1.5 g , but the latency between these events is longer for women compared to men. The X 2 a occurs immediately after incomplete glottal adduction. The emerging normative group latencies between the onset and offset of the acoustic and the GAW from this study appear promising for future investigations. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Adult onset of the Dandy-Walker syndrome.

PubMed

Lipton, H L; Preziosi, T J; Moses, H

1978-10-01

Two patients with the Dandy-Walker malformation first developed neurologic symptoms in adult life. In both patients there was normal motor and intellectual development during childhood, but as adults they had gradual evolution of brain stem and cerebellar signs and obstructive hydrocephalus. Following resection of the fourth ventricular cyst, both patients recovered. A review of the literature disclosed seven additional patients in whom the Dandy-Walker syndrome was first diagnosed in adult life. These cases illustrate that this congenital brain malformation may not only first become symptomatic later in life, but that it is possible for patients to remain asymptomatic.

Efficacy, tolerability, and retention rates of zonisamide in older adult patients with focal-onset epilepsy: Experiences from two tertiary epilepsy centers.

PubMed

Doğan, Ebru Apaydın; Genç, Emine; Genç, Bülent Oğuz; Erdoğan, Çağla

2017-11-01

The objective of this study was to evaluate the efficacy, tolerability, and retention rates for zonisamide (ZNS) in older adult patients with focal-onset epilepsy. Chart reviews of patients aged 60years and older with focal-onset epilepsy treated with ZNS in two tertiary epilepsy centers were analyzed retrospectively. Eighty-five patients (41 males, 44 females) aged over 60years (range: 60-81) with focal-onset epilepsy treated with ZNS were identified; 55.3% of the patients (n=47) were on monotherapy. The median and average doses of ZNS doses were 200mg/day (range: 100-400) and 212.9±84.2mg/day, respectively. With ZNS treatment, 67.1% of the patients (n=57) were seizure-free for a median of 28months (range: 10-56) whereas 20% (n=17) of the patients had seizures that were unresponsive to ZNS treatment. Best seizure control was achieved in patients with poststroke epilepsy; seizure freedom was 80% in this subgroup. Overall retention rate was found to be 83.5%. There was no significant relation between receiving poly- or monotherapy and discontinuation of ZNS (p=0.18). Thirty-two of the patients (37.6%) lost weight. Median weight loss was 8kg (range: 2-16). There was no significant correlation between weight loss and the administered doses of ZNS (r=0.34; p=0.12). Despite limitations due to the retrospective design of the study, the results show that ZNS is a well-retained drug with high efficacy in older adult patients with epilepsy. Copyright © 2017 Elsevier Inc. All rights reserved.

Early-onset growth hormone deficiency results in diastolic dysfunction in adult-life and is prevented by growth hormone supplementation.

PubMed

Groban, L; Lin, M; Kassik, K A; Ingram, R L; Sonntag, W E

2011-04-01

The primary goal of growth hormone (GH) replacement is to promote linear growth in children with growth hormone deficiency (GHD). GH and insulin-like growth factor-1 (IGF-1) are also known to have roles in cardiac development and as modulators of myocardial structure and function in the adult heart. However, little is known about cardiac diastolic function in young adults with childhood onset GH deficiency in which GH treatment was discontinued following puberty. The aim of the study was to evaluate the effects of long standing GHD and peri-pubertal or continuous GH replacement therapy on diastolic function in the adult dwarf rat. The dwarf rat, which possesses a mutation in a transcription factor necessary for development of the somatotroph, does not exhibit the normal peri-pubertal rise in GH around day 28 and was used to model childhood or early-onset GHD (EOGHD). In another group of male dwarfs, GH replacement therapy was initiated at 4 weeks of age when GH pulsatility normally begins. Ten weeks after initiation of injections, GH-treated dwarf rats were divided into 2 groups; continued treatment with GH for 12 weeks (GH-replete) or treatment with saline for 12 weeks. This latter group models GH supplementation during adolescence with GHD beginning in adulthood (adult-onset GHD; AOGHD). Saline-treated heterozygous (HZ) rats were used as age-matched controls. At 26 weeks of age, cardiac function was assessed using invasive or noninvasive (conventional and tissue Doppler) indices of myocardial contractility and lusitropy. Systolic function, as determined by echocardiography, was similar among groups. Compared with HZ rats and GH-replete dwarfs, the EOGHD group exhibited significant reductions in myocardial relaxation and increases in left ventricular filling pressure, indicative of moderate diastolic dysfunction. This was further associated with a decrease in the cardiac content of sarcoplasmic reticulum Ca(2+) ATPase (SERCA2), one of the important cardiac calcium

Prognosis of adult-onset idiopathic bile acid malabsorption.

PubMed

Rössel, P; Sortsøe Jensen, H; Qvist, P; Arveschoug, A

1999-06-01

From 1986 to 1993, 150 patients were investigated with the 75Se-homocholic acid taurine (SeHCAT) test as a late step in the investigation of chronic diarrhoea. On basis of low SeHCAT values and response to cholestyramine treatment, 33 patients were initially classified as having idiopathic bile acid malabsorption (IBAM). The aim was to describe the long-term clinical course of the disease and to assess the reliability of the SeHCAT test in diagnosing IBAM. The methods included 1) clinical follow-up with patient interview combined with information from medical records and 2) repeated SeHCAT test. The diagnosis of IBAM had to be revised in three cases (inflammatory bowel disease in two patients, Clostridium difficile infection in one). Six patients were lost to follow-up and a further four patients were excluded from re-examination either because of old age (>80 years) or bowel resection, leaving 20 patients for re-examination, of which 16 completed both clinical follow-up and a new SeHCAT test. The median duration of symptoms before initial SeHCAT test was 2.5 (1-30) years. In 13 of 16 patients symptoms persisted, and SeHCAT values remained low and almost identical to the initial value after a median observation time of 88 (51-113) months. Despite initial response to treatment with cholestyramine, six patients had to discontinue treatment because of adverse effects or other compliance problems. In three patients the SeHCAT value showed a considerable increase, and bowel function had correspondingly normalized in these cases. The study confirms the reliability of the SeHCAT test in diagnosing IBAM. Despite adult onset of symptoms, only a few patients improve after several years' observation. Treatment with cholestyramine is generally effective but not always tolerated.

Late-Onset N-Acetylglutamate Synthase Deficiency: Report of a Paradigmatic Adult Case Presenting with Headaches and Review of the Literature

PubMed Central

Cavicchi, Catia; Chilleri, Chiara; Fioravanti, Antonella; Ferri, Lorenzo; Ripandelli, Francesco; Costa, Cinzia; Calabresi, Paolo; Prontera, Paolo; Pochiero, Francesca; Pasquini, Elisabetta; Funghini, Silvia; la Marca, Giancarlo; Donati, Maria Alice

2018-01-01

N-acetylglutamate synthase deficiency (NAGSD) is an extremely rare urea cycle disorder (UCD) with few adult cases so far described. Diagnosis of late-onset presentations is difficult and delayed treatment may increase the risk of severe hyperammonemia. We describe a 52-year-old woman with recurrent headaches who experienced an acute onset of NAGSD. As very few papers focus on headaches in UCDs, we also report a literature review of types and pathophysiologic mechanisms of UCD-related headaches. In our case, headaches had been present since puberty (3–4 days a week) and were often accompanied by nausea, vomiting, or behavioural changes. Despite three previous episodes of altered consciousness, ammonia was measured for the first time at 52 years and levels were increased. Identification of the new homozygous c.344C>T (p.Ala115Val) NAGS variant allowed the definite diagnosis of NAGSD. Bioinformatic analysis suggested that an order/disorder alteration of the mutated form could affect the arginine-binding site, resulting in poor enzyme activation and late-onset presentation. After optimized treatment for NAGSD, ammonia and amino acid levels were constantly normal and prevented other headache bouts. The manuscript underlies that headache may be the presenting symptom of UCDs and provides clues for the rapid diagnosis and treatment of late-onset NAGSD. PMID:29364180

The clinical spectrum of late-onset Alexander disease: a systematic literature review.

PubMed

Balbi, Pietro; Salvini, Silvana; Fundarò, Cira; Frazzitta, Giuseppe; Maestri, Roberto; Mosah, Dibo; Uggetti, Carla; Sechi, GianPietro

2010-12-01

Following the discovery of glial fibrillary acidic protein (GFAP) mutations as the causative factor of Alexander disease (AxD), new case reports have recently increased, prompting a more detailed comprehension of the clinical features of the three disease subtypes (infantile, juvenile and adult). While the clinical pattern of the infantile form has been substantially confirmed, the late-onset subtypes (i.e., juvenile and adult), once considered rare manifestations of AxD, have displayed a wider clinical spectrum. Our aim was to evaluate the clinical phenotype of the adult and juvenile forms by reviewing the previously reported cases. Data were collected from previously published reports on 112 subjects affected by neuropathologically or genetically proven adult and juvenile Alexander disease. Although the late-onset forms of AxD show a wide clinical variability, a common pattern emerges from comparing previously reported cases, characterized by pseudo-bulbar signs, ataxia, and spasticity, associated with atrophy of the medulla and upper cervical cord on neuroimaging. Late-onset AxD cases can no longer be considered as rare manifestations of the disease. The clinical pattern usually reflects the topographic localization of the lesions, with adult cases displaying a predominant infratentorial localization of the lesions. Juvenile cases show clinical and radiological features which are intermediate between adult and infantile forms.

Comparative anti-androgenic actions of vinclozolin and flutamide on transgenerational adult onset disease and spermatogenesis.

PubMed

Anway, Matthew D; Rekow, Stephen S; Skinner, Michael K

2008-10-01

Exposure of gestating female rats to the anti-androgenic endocrine disruptor vinclozolin has been shown to induce transgenerational adult onset disease phenotypes. The current study, was designed to compare the actions of vinclozolin to the known anti-androgenic compound flutamide. The gestating female rats were exposed to intraperitoneal injections during embryonic day 8-14 (E8-E14) to 100mg/kg/day vinclozolin or flutamide at either 5mg or 20mg/kg/day. As previously observed, vinclozolin induced a transgenerational testis phenotype of increased spermatogenic cell apoptosis and decreased epididymal sperm number. In contrast, the flutamide exposures resulted in a testis phenotype of increased spermatogenic cell apoptosis and decreased epididymal sperm numbers in the F1 generation only, and not the F2 and F3 generation adult males. Interestingly, some of the low dose (5mg/kg) flutamide F2 generation offspring developed spinal agenesis and supernummery development (polymelia) of limbs. Although the actions of vinclozolin and flutamide appear similar in the F1 generation males, the transgenerational effects of vinclozolin do not appear to be acting through the same anti-androgenic mechanism as flutamide.

Comparative anti-androgenic actions of vinclozolin and flutamide on transgenerational adult onset disease and spermatogenesis

PubMed Central

Anway, Matthew D.; Rekow, Stephen S.; Skinner, Michael K.

2017-01-01

Exposure of gestating female rats to the anti-androgenic endocrine disruptor vinclozolin has been shown to induce transgenerational adult onset disease phenotypes. The current study, was designed to compare the actions of vinclozolin to the known anti-androgenic compound flutamide. The gestating female rats were exposed to intraperitoneal injections during embryonic day 8–14 (E8–E14) to 100 mg/kg/day vinclozolin or flutamide at either 5mg or 20 mg/kg/day. As previously observed, vinclozolin induced a transgenerational testis phenotype of increased spermatogenic cell apoptosis and decreased epididymal sperm number. In contrast, the flutamide exposures resulted in a testis phenotype of increased spermatogenic cell apoptosis and decreasedepididymal spermnumbers in the F1 generation only, and not the F2 and F3 generation adult males. Interestingly, some of the lowdose (5 mg/kg) flutamide F2 generation offspring developed spinal agenesis and supernummery development (polymelia) of limbs. Although the actions of vinclozolin and flutamide appear similar in the F1 generation males, the transgenerational effects of vinclozolin do not appear to be acting through the same anti-androgenic mechanism as flutamide. PMID:18762243

Management of adult-onset methylmalonic acidemia with hypotonia and acute respiratory failure: A case report.

PubMed

Zhao, Zhanqi; Chu, Chan-Ching; Chang, Mei-Yun; Chang, Hao-Tai; Hsu, Yeong-Long

2018-06-01

Methylmalonic acidemia (MMA) is an autosomal recessive disease of organic acidemia. We report a 26-year-old male who presented with metabolic acidosis, acute renal failure required hemodialysis and acute respiratory failure required mechanical ventilation support. Progressive hypotonia of muscles made weaning from mechanical ventilator difficult. High level of serum methylmalonic acid and the mut genotype sequences confirmed the diagnosis of this adult-onset MMA. Two mut genotype sequences were found by analyzing all coding exons and exon-intron junctions. One genotype was well documented (Exon 6 Mutation, c. 1280G>A. p. G427D, heterozygous). The other mut genotype sequence had never been reported elsewhere (Intron 6 Novel, c. 1333-13_c. 1333-8delTTTTTC, heterozygous). Diet modification, medication, regular hemodialysis and physical rehabilitation. Weaning strategy adjusted with help of electrical impedance tomography. The muscle power of the patient gradually recovered. Extubation of the patient was successful and he was discharged without oxygen required. This case gives us the lesson that MMA can be newly diagnosed in adult patient. A new mut genotype sequence was discovered. The use of electrical impedance tomography to select a suitable method for inspiratory muscle training was possible and useful.

Using digital technologies to engage with medical research: views of myotonic dystrophy patients in Japan.

PubMed

Coathup, Victoria; Teare, Harriet J A; Minari, Jusaku; Yoshizawa, Go; Kaye, Jane; Takahashi, Masanori P; Kato, Kazuto

2016-08-24

As in other countries, the traditional doctor-patient relationship in the Japanese healthcare system has often been characterised as being of a paternalistic nature. However, in recent years there has been a gradual shift towards a more participatory-patient model in Japan. With advances in technology, the possibility to use digital technologies to improve patient interactions is growing and is in line with changing attitudes in the medical profession and society within Japan and elsewhere. The implementation of an online patient engagement platform is being considered by the Myotonic Dystrophy Registry of Japan. The aim of this exploratory study was to understand patients' views and attitudes to using digital tools in patient registries and engagement with medical research in Japan, prior to implementation of the digital platform. We conducted an exploratory, cross-sectional, self-completed questionnaire with a sample of myotonic dystrophy (MD) patients attending an Open Day at Osaka University, Japan. Patients were eligible for inclusion if they were 18 years or older, and were diagnosed with MD. A total of 68 patients and family members attended the Open Day and were invited to participate in the survey. Of those, 59 % submitted a completed questionnaire (n = 40). The survey showed that the majority of patients felt that they were not receiving the information they wanted from their clinicians, which included recent medical research findings and opportunities to participate in clinical trials, and 88 % of patients indicated they would be willing to engage with digital technologies to receive relevant medical information. Patients also expressed an interest in having control over when and how they received this information, as well as being informed of how their data is used and shared with other researchers. Overall, the findings from this study suggest that there is scope to develop a digital platform to engage with patients so that they can receive

Transitioning and Transfer of Adolescents and Young Adults with Pediatric Onset Chronic Disease: The Patient and Parent Perspective

PubMed Central

Fernandes, Susan M.; O’Sullivan-Oliveira, Joanne; Landzberg, Michael J.; Khairy, Paul; Melvin, Patrice; Sawicki, Gregory S.; Ziniel, Sonja; Kenney, Lisa B.; Garvey, Katharine C.; Sobota, Amy; O’Brien, Rebecca; Nigrovic, Peter A.; Sharma, Niraj; Fishman, Laurie N

2017-01-01

Purpose To determine patients’ and parents’ perceptions of transitioning education as well as their attitudes and perceived barriers to transfer to adult oriented care. Methods A self-report survey was administered to patients (16–25 years old) with various childhood onset chronic diseases. A similar survey was administered to their parents/guardians. Results A total of 155 patients and 104 parents participated in the study. The mean age of patients was 18.9±2.3 years; 57% were female. Although most patients and parents reported receiving information and training about their medical condition, significant gaps in “transitioning education” were identified. These included stated deficiencies in education regarding unprotected intercourse, health of future offspring, birth control, pregnancy, illicit drug use, and future career or vocation counseling. Commonly named barriers to transfer were emotional attachments and lack of adult medicine specialty providers; however, the majority anticipated being ready to transfer to adult oriented care by age 25 years. Conclusion Current transitioning education delivery appears to result in significant gaps in transfer of information and training, as perceived by patients and their parents. Standardization of transitioning education may help ensure that patients obtain the necessary skills for self-care in adulthood and successful transfer to adult oriented care. PMID:24919937

Maternal exposure to di(2-ethylhexyl)phthalate (DEHP) promotes the transgenerational inheritance of adult-onset reproductive dysfunctions through the female germline in mice.

PubMed

Pocar, Paola; Fiandanese, Nadia; Berrini, Anna; Secchi, Camillo; Borromeo, Vitaliano

2017-05-01

Endocrine disruptors (EDs) are compounds known to promote transgenerational inheritance of adult-onset disease in subsequent generations after maternal exposure during fetal gonadal development. This study was designed to establish whether gestational and lactational exposure to the plasticizer di(2-ethylhexyl)phthalate (DEHP) at environmental doses promotes transgenerational effects on reproductive health in female offspring, as adults, over three generations in the mouse. Gestating F0 mouse dams were exposed to 0, 0.05, 5mg/kg/day DEHP in the diet from gestational day 0.5 until the end of lactation. The incidence of adult-onset disease in reproductive function was recorded in F1, F2 and F3 female offspring. In adult F1 females, DEHP exposure induced reproductive adverse effects with: i) altered ovarian follicular dynamics with reduced primordial follicular reserve and a larger growing pre-antral follicle population, suggesting accelerated follicular recruitment; ii) reduced oocyte quality and embryonic developmental competence; iii) dysregulation of the expression profile of a panel of selected ovarian and pre-implantation embryonic genes. F2 and F3 female offspring displayed the same altered reproductive morphological phenotype and gene expression profiles as F1, thus showing transgenerational transmission of reproductive adverse effects along the female lineage. These findings indicate that in mice exposure to DEHP at doses relevant to human exposure during gonadal sex determination significantly perturbs the reproductive indices of female adult offspring and subsequent generations. Evidence of transgenerational transmission has important implications for the reproductive health and fertility of animals and humans, significantly increasing the potential biohazards of this toxicant. Copyright © 2017 Elsevier Inc. All rights reserved.

Balance outcomes following a tap dance program for a child with congenital myotonic muscular dystrophy.

PubMed

Biricocchi, Charlanne; Drake, JaimeLynn; Svien, Lana

2014-01-01

This case report describes the effects of a 6-week progressive tap dance program on static and dynamic balance for a child with type 1 congenital myotonic muscular dystrophy (congenital MMD1). A 6-year-old girl with congenital MMD1 participated in a 1-hour progressive tap dance program. Classes were held once a week for 6 consecutive weeks and included 3 children with adaptive needs and 1 peer with typical development. The Bruininks-Oseretsky Test of Motor Proficiency, second edition (BOT-2) balance subsection and the Pediatric Balance Scale were completed at the beginning of the first class and the sixth class. The participant's BOT-2 score improved from 3 to 14. Her Pediatric Balance Scale score did not change. Participation in a progressive tap dance class by a child with congenital MMD1 may facilitate improvements in static and dynamic balance.

ZNF9 Activation of IRES-Mediated Translation of the Human ODC mRNA Is Decreased in Myotonic Dystrophy Type 2

PubMed Central

Sammons, Morgan A.; Antons, Amanda K.; Bendjennat, Mourad; Udd, Bjarne; Krahe, Ralf; Link, Andrew J.

2010-01-01

Myotonic dystrophy types 1 and 2 (DM1 and DM2) are forms of muscular dystrophy that share similar clinical and molecular manifestations, such as myotonia, muscle weakness, cardiac anomalies, cataracts, and the presence of defined RNA-containing foci in muscle nuclei. DM2 is caused by an expansion of the tetranucleotide CCTG repeat within the first intron of ZNF9, although the mechanism by which the expanded nucleotide repeat causes the debilitating symptoms of DM2 is unclear. Conflicting studies have led to two models for the mechanisms leading to the problems associated with DM2. First, a gain-of-function disease model hypothesizes that the repeat expansions in the transcribed RNA do not directly affect ZNF9 function. Instead repeat-containing RNAs are thought to sequester proteins in the nucleus, causing misregulation of normal cellular processes. In the alternative model, the repeat expansions impair ZNF9 function and lead to a decrease in the level of translation. Here we examine the normal in vivo function of ZNF9. We report that ZNF9 associates with actively translating ribosomes and functions as an activator of cap-independent translation of the human ODC mRNA. This activity is mediated by direct binding of ZNF9 to the internal ribosome entry site sequence (IRES) within the 5′UTR of ODC mRNA. ZNF9 can activate IRES-mediated translation of ODC within primary human myoblasts, and this activity is reduced in myoblasts derived from a DM2 patient. These data identify ZNF9 as a regulator of cap-independent translation and indicate that ZNF9 activity may contribute mechanistically to the myotonic dystrophy type 2 phenotype. PMID:20174632

Characteristics of New-Onset and Chronic Sleep Medication Users Among Older Adults: A Retrospective Study of a US Medigap Plan Population using Propensity Score Matching.

PubMed

Musich, Shirley; Wang, Shaohung S; Slindee, Luke B; Saphire, Lynn; Wicker, Ellen

2018-05-01

Prescription sleep medications are often utilized to manage sleep problems among older adults even though these drugs are associated with multiple risks. The aim was to determine the prevalence and characteristics of new-onset compared to chronic sleep medication users and to examine factors associated with the conversion from new to chronic use. A secondary objective was to investigate the impact of sleep medications on health outcomes of injurious falls and patterns of healthcare utilization and expenditures. A 25% random sample of adults ≥ 65 years with 3-year continuous AARP ® Medicare Supplement medical and AARP ® MedicareRx drug plan enrollment was utilized to identify new-onset and chronic sleep medication users. Prescription sleep medication drugs were defined using National Drug Codes (NDCs); falls or hip fractures were identified from diagnosis codes. New users had no sleep medication use in 2014, but initiated medication use in 2015; chronic users had at least one sleep medication prescription in 2014 and in 2015; both groups had follow-up through 2016. Characteristics associated with new users, new users who converted to chronic use, and chronic users were determined using multivariate logistic regression. Prevalence of falls, healthcare utilization and expenditures were regression adjusted. Among eligible insureds, 3 and 9% were identified as new-onset and chronic sleep medication users, respectively. New-onset sleep medication prescriptions were often associated with an inpatient hospitalization. The strongest characteristics associated with new users, those who converted to chronic use, and chronic users were sleep disorders, depression and opioid use. About 50% of new users had > 30 days' supply; 25% converted to chronic use with ≥ 90 days' supply. The prevalence of falls for new-onset users increased by 70% compared to a 22% increase among chronic users. New-onset and chronic sleep medication users were characterized by sleep

A preliminary study of the influence of age of onset and childhood trauma on cortical thickness in major depressive disorder.

PubMed

Jaworska, Natalia; MacMaster, Frank P; Gaxiola, Ismael; Cortese, Filomeno; Goodyear, Bradley; Ramasubbu, Rajamannar

2014-01-01

Major depressive disorder (MDD) neural underpinnings may differ based on onset age and childhood trauma. We assessed cortical thickness in patients who differed in age of MDD onset and examined trauma history influence. Adults with MDD (N=36) and controls (HC; N=18) underwent magnetic resonance imaging. Twenty patients had MDD onset<24 years of age (pediatric onset) and 16 had onset>25 years of age (adult onset). The MDD group was also subdivided into those with (N=12) and without (N=19) physical and/or sexual abuse as assessed by the Childhood Trauma Questionnaire (CTQ). Cortical thickness was analyzed with FreeSurfer software. Thicker frontal pole and a tendency for thinner transverse temporal cortices existed in MDD. The former was driven by the pediatric onset group and abuse history (independently), particularly in the right frontal pole. Inverse correlations existed between CTQ scores and frontal pole cortex thickness. A similar inverse relation existed with left inferior and right superior parietal cortex thickness. The superior temporal cortex tended to be thinner in pediatric versus adult onset groups with childhood abuse. This preliminary work suggests neural differences between pediatric and adult MDD onset. Trauma history also contributes to cytoarchitectural modulation. Thickened frontal pole cortices as a compensatory mechanism in MDD warrant evaluation.

Adult onset Still's disease and collapsing glomerulopathy: successful treatment with intravenous immunoglobulins and mycophenolate mofetil.

PubMed

Bennett, A N; Peterson, P; Sangle, S; Hangartner, R; Abbs, I C; Hughes, G R V; D'Cruz, D P

2004-06-01

In this Grand Round we present a 32-yr-old African man who became severely ill after a 5-month history of weight loss, pyrexia, arthralgia, sweats and rash. He went on to develop pericarditis, pericardial effusion with tamponade, hepatomegaly with abnormal liver function tests, lymphadenopathy, massive proteinuria and required ventilatory, circulatory and renal support. The differential diagnosis was adult onset Still's disease, systemic lupus erythematosus (SLE), infection and lymphoma. Primary infection and lymphoma were excluded and he was treated, with dramatic success, with intravenous immunoglobulins (i.v.IG). Subsequent renal biopsy excluded SLE but confirmed collapsing glomerulopathy. The proteinuria improved dramatically following treatment with mycophenolate mofetil. We discuss some of the difficult diagnostic and management issues raised by this patient and the different uses and mechanisms of action of i.v.IG.

Change in plasma Aß peptides and onset of dementia in adults with Down syndrome.

PubMed

Schupf, N; Zigman, W B; Tang, M-X; Pang, D; Mayeux, R; Mehta, P; Silverman, W

2010-11-02

To examine changes in levels of plasma amyloid-β (Aβ) peptides, Aβ42 and Aβ40, in relation to onset of Alzheimer disease (AD) in adults with Down syndrome (DS). Plasma Aβ42 and Aβ40 were measured at initial examination and at follow-up in a community-based cohort of 225 adults with DS who did not have dementia at baseline and were assessed for cognitive/functional abilities and health status and followed at 14- to 20-month intervals. We used Cox proportional hazards modeling to estimate the cumulative incidence of AD by Aβ peptide change group (increasing, no change, or decreasing), adjusting for covariates. Sixty-one (27.1%) of the participants developed AD. At follow-up, a decrease in Aβ42 levels, a decrease in the Aβ42/Aβ40 ratio, and an increase in Aβ40 levels were related to conversion to AD. Compared with the group with increasing levels of Aβ42, the likelihood of developing AD was 5 times higher for those whose plasma Aβ42 levels decreased over follow-up (hazard ratio [HR] = 4.9, 95% confidence interval [CI] 2.1-11.4). Decreasing Aβ42/Aβ40 was also strongly related to AD risk (HR = 4.9, 95% CI 1.8-13.2), while decreasing Aβ40 was associated with lower risk (HR = 0.4, 95% CI 0.2-0.9). Among adults with DS, decreasing levels of plasma Aβ42, a decline in the Aβ42/Aβ40 ratio, or increasing levels of Aβ40 may be sensitive indicators of conversion to AD, possibly reflecting compartmentalization of Aβ peptides in the brain.

Disturbed sleep as risk factor for the subsequent onset of bipolar disorder--Data from a 10-year prospective-longitudinal study among adolescents and young adults.

PubMed

Ritter, Philipp S; Höfler, Michael; Wittchen, Hans-Ulrich; Lieb, Roselind; Bauer, Michael; Pfennig, Andrea; Beesdo-Baum, Katja

2015-09-01

There is ample data suggesting that individuals with bipolar disorder more frequently suffer from disturbed sleep even when euthymic. Since sleep is a process that is crucial for affective homeostasis, disturbed sleep in healthy individuals may be a risk factor for the subsequent onset of bipolar disorder. Utilizing data from a large cohort of adolescents and young adults, this study tests the hypothesis that disturbed sleep constitutes a risk factor for the later onset of bipolar disorder. A representative community sample of N = 3021 adolescents and young adults (baseline age 14-24) was assessed using the standardized Composite International Diagnostic Interview and followed-up prospectively up to 3 times over up to 10 years. Disturbed sleep at baseline was quantified utilizing the corresponding items from the self-report inventory SCL-90-R. The compound value (insomnia-score) as an ordinal parameter for the severity of sleep disturbances was used to assess associations with the incidence of bipolar disorder among participants free of major mental disorder at baseline (N = 1943) using odds ratios (OR) from logistic regressions. Analyses were adjusted for age, gender, parental mood disorder and lifetime alcohol or cannabis dependence. Poor sleep quality significantly increased the risk for the subsequent development of bipolar disorder (OR = 1.75; p = 0.001). Regarding individual sleep items, trouble falling asleep and early morning awakening were predictive for the subsequent onset of bipolar disorder. Disturbed sleep in persons otherwise free of major mental disorders appears to confer an increased risk for the subsequent onset of bipolar disorder. Copyright © 2015 Elsevier Ltd. All rights reserved.

Primary caregivers' awareness and perception of early-onset dementia conditions in adolescents and young and middle-aged adults with Down syndrome.

PubMed

Lin, Jin-Ding; Chen, Wen-Xiu; Hsu, Shang-Wei; Lin, Lan-Ping; Lin, Fu-Gong; Tang, Chi-Chieh; Wu, Jia-Ling; Chu, Cordia; Chou, Yu-Ching

2014-09-01

The present study aims to investigate the onset of dementia conditions using the Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID) scale and to identify the possible factors associated with DSQIID scores in people with Down syndrome (DS). The study population was recruited from the voluntary registry members of the Republic of China Foundation for Persons with Down syndrome; primary caregivers provided DSQIID information on 196 adolescents and adults with DS (aged 15-48 years) who were entered into the database and analyzed using SPSS 20.0 software. The results described the distribution of early-onset dementia conditions in 53 adolescents and adults with DS, and 2.6% of the subjects with DS had possible dementia (DSQIID score ≧ 20). Univariate analyses found that older age (p=0.001) and comorbid conditions (p=0.003) were significantly associated with DSQIID scores. Older subjects were more likely to have higher DSQIID scores than were younger age groups after ANOVA and Scheffe's tests. Lastly, a multiple linear regression analysis revealed that age (p<0.01), severe disability level (p<0.05) and comorbid condition (p<0.01) significantly explained 13% of the variation in DSQIID scores after adjusting for the factors of gender, education level and multiple disabilities in adolescents and adults with DS. The study highlights that future research should focus on the occurrence of dementia in people with DS and on identifying its influencing factors based on sound measurements, to initiate appropriate healthy aging policies for this group of people. Copyright © 2014 Elsevier Ltd. All rights reserved.

Perinatal exposure to environmental tobacco smoke is associated with changes in DNA methylation that precede the adult onset of lung disease in a mouse model.

PubMed

Cole, Elizabeth; Brown, Traci A; Pinkerton, Kent E; Postma, Britten; Malany, Keegan; Yang, Mihi; Kim, Yang Jee; Hamilton, Raymond F; Holian, Andrij; Cho, Yoon Hee

2017-08-01

Prenatal and early-life environmental tobacco smoke (ETS) exposure can induce epigenetic alterations associated with inflammation and respiratory disease. The objective of this study was to address the long-term epigenetic consequences of perinatal ETS exposure on latent respiratory disease risk, which are still largely unknown. C57BL/6 mice were exposed to prenatal and early-life ETS; offspring lung pathology, global DNA, and gene-specific methylation were measured at two adult ages. Significant alterations in global DNA methylation and promoter methylation of IFN-γ and Thy-1 were found in ETS-exposed offspring at 10-12 and 20 weeks of age. These sustained epigenetic alterations preceded the onset of significant pulmonary pathologies observed at 20 weeks of age. This study suggests that perinatal ETS exposure induces persistent epigenetic alterations in global DNA, as well as IFN-γ and Thy-1 promoter methylation that precede the adult onset of fibrotic lung pathology. These epigenetic findings could represent potential biomarkers of latent respiratory disease risk.

A case of adult-onset reducing body myopathy presenting a novel clinical feature, asymmetrical involvement of the sternocleidomastoid and trapezius muscles.

PubMed

Fujii, Takayuki; Hayashi, Shintaro; Kawamura, Nobutoshi; Higuchi, Masa-Aki; Tsugawa, Jun; Ohyagi, Yasumasa; Hayashi, Yukiko K; Nishino, Ichizo; Kira, Jun-Ichi

2014-08-15

We herein report a 32-year-old woman with adult-onset reducing body myopathy (RBM) who had a mutation in the four-and-a-half LIM domain 1 gene (FHL1) and showed a marked asymmetrical involvement of sternocleidomastoid and trapezius muscles. At 30 years of age she noticed bilateral foot drop, and over the next two years developed difficulty raising her right arm. At 32 years of age she was admitted to our hospital for a diagnostic evaluation. Neurological examination showed moderate weakness and atrophy of her right sternocleidomastoid muscle, right trapezius muscle, and bilateral upper proximal muscles. There were severe weakness and atrophy of her bilateral tibialis anterior muscles. Her deep tendon reflexes were hypoactive in her upper extremities. Her serum creatine kinase level was mildly increased. Muscle biopsy specimens from the left tibialis anterior muscle revealed marked variation in fiber size, some necrotic or regenerating fibers, and reducing bodies. Gene analysis of FHL1 demonstrated a mutation: a heterozygous missense mutation of c.377G>A (p. C126T) in FHL1. Compared with previous adult-onset RBM cases harboring mutations in FHL1, our case was characterized by asymmetrical atrophy of the sternocleidomastoid and trapezius muscles. Copyright © 2014 Elsevier B.V. All rights reserved.

Children's Acquisition of English Onset and Coda /l/: Articulatory Evidence

PubMed Central

Demuth, Katherine

2015-01-01

Purpose The goal of this study was to better understand how and when onset /l/ (leap) and coda /l/ (peel) are acquired by children by examining both the articulations involved and adults' perceptions of the produced segments. Method Twenty-five typically developing Australian English–speaking children aged 3;0 (years;months) to 7;11 participated in an elicited imitation task, during which audio, video, and lingual ultrasound images were collected. Transcribers perceptually rated audio, whereas video and ultrasound images were visually examined for the presence of adult-like articulations. Results Data from this study establish that for Australian English–learning children, coda /l/s are acquired later than onset /l/s, and older children produce greater proportions of adultlike /l/s in both onset and coda positions, roughly following established norms for American English–speaking children. However, although perceptibility of coda /l/s was correlated with their articulations, onset /l/s were nearly uniformly perceived as adultlike despite substantial variation in the articulations used to produce them. Conclusions The disparity in the production and perception of children's singleton onset /l/s is linked to both physiological and phonological development. Suggestions are made for future research to tease these factors apart. PMID:25321384

Time-to-onset and -resolution of adverse events before/after atomoxetine discontinuation in adult patients with ADHD.

PubMed

Upadhyaya, Himanshu; Tanaka, Yoko; Lipsius, Sarah; Kryzhanovskaya, Ludmila A; Lane, Jeannine R; Escobar, Rodrigo; Trzepacz, Paula T; Allen, Albert J

2015-01-01

Adults with attention-deficit/hyperactivity disorder treated with atomoxetine were examined for time-to-onset and -resolution of common treatment-emergent adverse events (TEAEs) and male sexual dysfunction, and for changes in blood pressure (BP) and heart rate (HR) upon atomoxetine discontinuation. 12-week open-label atomoxetine (40-100 mg/day) was followed by 12-week double-blind maintenance treatment (atomoxetine 80 or 100 mg/day). Responders were then randomized to atomoxetine (n = 266) or placebo (n = 258) for 25-week randomized withdrawal. Examined were (1) median time-to-onset and -resolution of TEAEs during atomoxetine treatment, and (2) within group, visitwise mean changes for sitting HR, systolic BP, and diastolic BP for the postrandomization placebo group. Common adverse events (AEs) appeared early, within week 1 of atomoxetine treatment. Some AEs resolve relatively rapidly, whereas others have a more lingering course of resolution (including male sexual side effects); median resolution times were 3 - 53 days. BP and HR increases during atomoxetine treatment returned to baseline upon atomoxetine discontinuation. Atomoxetine is associated with common AEs, with 3- to 53-day median resolution times. ClincialTrials.gov - NCT00700427.

A polymorphism in the MSH3 mismatch repair gene is associated with the levels of somatic instability of the expanded CTG repeat in the blood DNA of myotonic dystrophy type 1 patients.

PubMed

Morales, Fernando; Vásquez, Melissa; Santamaría, Carolina; Cuenca, Patricia; Corrales, Eyleen; Monckton, Darren G

2016-04-01

Somatic mosaicism of the expanded CTG repeat in myotonic dystrophy type 1 is age-dependent, tissue-specific and expansion-biased, contributing toward the tissue-specificity and progressive nature of the symptoms. Previously, using regression modelling of repeat instability we showed that variation in the rate of somatic expansion in blood DNA contributes toward variation in age of onset, directly implicating somatic expansion in the disease pathway. Here, we confirm these results using a larger more genetically homogenous Costa Rican DM1 cohort (p<0.001). Interestingly, we also provide evidence that supports subtle sex-dependent differences in repeat length-dependent age at onset and somatic mutational dynamics. Previously, we demonstrated that variation in the rate of somatic expansion was a heritable quantitative trait. Given the important role that DNA mismatch repair genes play in mediating expansions in mouse models, we tested for modifier gene effects with 13 DNA mismatch gene polymorphisms (one each in MSH2, PMS2, MSH6 and MLH1; and nine in MSH3). After correcting for allele length and age effects, we identified three polymorphisms in MSH3 that were associated with variation in somatic instability: Rs26279 (p=0.003); Rs1677658 (p=0.009); and Rs10168 (p=0.031). However, only the association with Rs26279 remained significant after multiple testing correction. Although we revealed a statistically significant association between Rs26279 and somatic instability, we did not detect an association with the age at onset. Individuals with the A/A genotype for Rs26279 tended to show a greater propensity to expand the CTG repeat than other genotypes. Interestingly, this SNP results in an amino acid change in the critical ATPase domain of MSH3 and is potentially functionally dimorphic. These data suggest that MSH3 is a key player in generating somatic variation in DM1 patients and further highlight MSH3 as a potential therapeutic target. Copyright © 2016 Elsevier B

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

PubMed

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

2008-03-15

Obsessive-compulsive disorder (OCD) often emerges in childhood or adolescence. The aim of the present study was to evaluate whether adult patients with prepuberal onset differ from subjects with later onset in terms of personality disorder comorbidity. The Structured Clinical Interview for DSM-IV Axis II Disorders was used to assess 148 patients with a principal diagnosis of OCD according to the Structured Clinical Interview for DSM-IV Axis I Disorders. The following two subgroups of subjects were selected according to the age at onset of symptomatology: patients with an early-onset (< or =10 years), and patients with a later onset (> or =17 years). Of the 148 patients screened for the present study, 33 (22.3%) had an early onset and 1369 (46.6%) had a later onset. With regard to personality disorders, early-onset patients showed more OC personality disorders (OCPD) than later onset patients. Our finding suggests that OCD in childhood increases the risk for developing OCPD in adulthood, or that early-onset OCD and OCPD share a common pathogenesis.

Vapor, Dust and Smoke Exposure in relation to adult-onset asthma and chronic respiratory symptoms: The Singapore Chinese Health Study

PubMed Central

LeVan, Tricia D.; Koh, Woon-Puay; Lee, Hin-Peng; Koh, David; Yu, Mimi C.; London, Stephanie J.

2006-01-01

Occupational factors contribute to a significant fraction of respiratory disease and symptoms. We evaluated the role of occupational exposures on asthma, chronic bronchitis, and respiratory symptoms in a population-based cohort, the Singapore Chinese Health Study. History of occupations, occupational exposures, and respiratory conditions were collected by interviews with 52,325 Singaporeans born 1918–1953. Exposure to dusts, from cotton, wood, metal, mineral and/or asbestos, was associated with non-chronic cough and/or phlegm (OR = 1.19, 95% CI = 1.08, 1.30), chronic bronchitis (OR = 1.26, 95% CI = 1.01, 1.57) and adult-onset asthma (OR = 1.14, 95% CI = 1.00, 1.30). Cotton dust was the major component contributing to respiratory symptoms. Vapor exposure, from chemical solvents, dyes, cooling oils, paints, wood preservatives and/or pesticides, was associated with non-chronic cough or phlegm (OR = 1.14, 95% CI = 1.03, 1.27), chronic dry cough (OR = 1.55, 95% CI = 1.19, 2.01) and adult-onset asthma (OR = 1.34, 95% CI = 1.15, 1.56). Chemical solvents, cooling oils and pesticides were the major sources contributing to respiratory symptoms. These data support the role of occupational exposures in the etiology of respiratory illness in a population-based cohort in Singapore with a low prevalence of atopic illness. PMID:16707657

Detection of linkage disequilibrium between the myotonic dystrophy locus and a new polymorphic DNA marker.

PubMed Central

Harley, H G; Brook, J D; Floyd, J; Rundle, S A; Crow, S; Walsh, K V; Thibault, M C; Harper, P S; Shaw, D J

1991-01-01

We have examined the linkage of two new polymorphic DNA markers (D19S62 and D19S63) and a previously unreported polymorphism with an existing DNA marker (ERCC1) to the myotonic dystrophy (DM) locus. In addition, we have used pulsed-field gel electrophoresis to obtain a fine-structure map of this region. The detection of linkage disequilibrium between DM and one of these markers (D19S63) is the first demonstration of this phenomenon in a heterogeneous DM population. The results suggest that at least 58% of DM patients in the British population, as well as those in a French-Canadian subpopulation, are descended from the same ancestral DM mutation. We discuss the implications of this finding in terms of strategies for cloning the DM gene, for a possible role in modification of risk for prenatal and presymptomatic testing, and we speculate on the origin and number of existing mutations which may result in a DM phenotype. PMID:2063878

Myotonic Dystrophy Type 2 Found in Two of Sixty-Three Persons Diagnosed as Having Fibromyalgia

PubMed Central

Auvinen, Satu; Suominen, Tiina; Hannonen, Pekka; Bachinski, Linda L.; Krahe, Ralf; Udd, Bjarne

2008-01-01

Because of its high prevalence, fibromyalgia (FM) is a major general health issue. Myotonic dystrophy type 2 (DM2) is a recently described autosomal-dominant multisystem disorder. Besides variable proximal muscle weakness, myotonia, and precocious cataracts, muscle pain and stiffness are prominent presenting features of DM2. After noting that several of our mutation-positive DM2 patients had a previous diagnosis of FM, suggesting that DM2 may be misdiagnosed as FM, we invited 90 randomly selected patients diagnosed as having FM to undergo genetic testing for DM2. Of the 63 patients who agreed to participate, 2 (3.2%) tested positive for the DM2 mutation. Their cases are described herein. DM2 was not found in any of 200 asymptomatic controls. We therefore suggest that the presence of DM2 should be investigated in a large sample of subjects diagnosed as having FM, and clinicians should be aware of overlap in the clinical presentation of these 2 distinct disorders. PMID:18975316

Case of adult-onset neuronal intranuclear hyaline inclusion disease with negative electroretinogram.

PubMed

Yamada, Wataru; Takekoshi, Akira; Ishida, Kyoko; Mochizuki, Kiyofumi; Sone, Jun; Sobue, Gen; Hayashi, Yuichi; Inuzuka, Takashi; Miyake, Yozo

2017-06-01

To report the findings in a 72-year-old man with neuronal intranuclear hyaline inclusion disease (NIHID) with the negative-type electroretinogram (ERG) and without night blindness. Standard ophthalmological examinations including the medical history, measurements of the best-corrected visual acuity and intraocular pressures, slit-lamp biomicroscopy, ophthalmoscopy, spectral-domain optical coherence tomography, fundus autofluorescence, and perimetry were performed. In addition, neurological and electrophysiological examinations were performed. NIHID was confirmed by skin biopsy. The ophthalmologic examinations revealed sluggish pupillary reflexes without visual disturbances and retinal abnormalities. The amplitudes of the dark-adapted 0.01 ERG was absent, and light-adapted 3 ERG and light-adapted 30 Hz flicker ERG were reduced in amplitude and delayed in implicit time. The rod system was more severely affected than the cone system, indicating that NIHID is classified as one of rod-cone dysfunction syndrome. The dark-adapted 3 ERG consisted of a markedly reduced b-wave with larger a-wave (negative ERG), but the amplitude of a-wave was smaller than normal. Since the ophthalmoscopical findings and the subjective visual functions may be essentially normal, the characteristic ERG abnormalities can be an important findings in adult-onset NIHID without night blindness.

Facial emotion recognition in childhood-onset bipolar I disorder: an evaluation of developmental differences between youths and adults

PubMed Central

Wegbreit, Ezra; Weissman, Alexandra B; Cushman, Grace K; Puzia, Megan E; Kim, Kerri L; Leibenluft, Ellen; Dickstein, Daniel P

2015-01-01

Objectives Bipolar disorder (BD) is a severe mental illness with high healthcare costs and poor outcomes. Increasing numbers of youths are diagnosed with BD, and many adults with BD report their symptoms started in childhood, suggesting BD can be a developmental disorder. Studies advancing our understanding of BD have shown alterations in facial emotion recognition in both children and adults with BD compared to healthy comparison (HC) participants, but none have evaluated the development of these deficits. To address this, we examined the effect of age on facial emotion recognition in a sample that included children and adults with confirmed childhood-onset type-I BD, with the adults having been diagnosed and followed since childhood by the Course and Outcome in Bipolar Youth study. Methods Using the Diagnostic Analysis of Non-Verbal Accuracy, we compared facial emotion recognition errors among participants with BD (n = 66; ages 7–26 years) and HC participants (n = 87; ages 7–25 years). Complementary analyses investigated errors for child and adult faces. Results A significant diagnosis-by-age interaction indicated that younger BD participants performed worse than expected relative to HC participants their own age. The deficits occurred for both child and adult faces and were particularly strong for angry child faces, which were most often mistaken as sad. Our results were not influenced by medications, comorbidities/substance use, or mood state/global functioning. Conclusions Younger individuals with BD are worse than their peers at this important social skill. This deficit may be an important developmentally salient treatment target, i.e., for cognitive remediation to improve BD youths’ emotion recognition abilities. PMID:25951752

Consequences of stopping growth hormone (GH) therapy in young GH deficient patients with childhood onset disease.

PubMed

Juul, A; Vahl, N; Jørgensen, J O; Christiansen, J S; Sneppen, S B; Feldt-Rasmussen, U; Skakkebaek, N E

1998-02-01

Many studies have shown the beneficial, anabolic effects of growth hormone (GH) replacement therapy in GH deficient adults with childhood onset or adult onset disease. It is becoming increasingly evident, however, that these two groups of patients differ in many respects. Patients with adult onset GH deficiency represent fully developed individuals who have various organic, cerebral defects. By contrast, patients with childhood onset disease represent a heterogenous group comprising individuals with conditions, such as idiopathic isolated GH deficiency, genetic defects and organic defects. It is generally accepted that all children treated with GH should be retested in adulthood before adult replacement is started, as around 40% have a normal retest. It is unclear whether continued treatment with GH in childhood onset GH deficiency will yield results as positive as those seen in trials where GH is re-instituted after longer periods without treatment. Similarly, it is unknown at what timepoint cessation of GH treatment will cause a worsening in the physical state of the patient. In our placebo-controlled trial where GH was discontinued in 19 patients treated with GH during childhood, we determined exercise capacity, body composition, muscle mass and strength, cardiac function, sweating capacity, thyroid function and glucose metabolism before and after 12 months of continued treatment with GH.

Protective connections and educational attainment among young adults with childhood-onset chronic illness.

PubMed

Maslow, Gary; Haydon, Abigail A; McRee, Annie-Laurie; Halpern, Carolyn T

2012-08-01

Youth with childhood-onset chronic illness (COCI) are at risk of poor educational attainment. Specific protective factors that promote college graduation in this population have not been studied previously. In this study, we examine the role protective factors during adolescence play in promoting college graduation among young adults with COCI. Data were collected from 10,925 participants in the National Longitudinal Study of Adolescent Health (Add Health). Protective factors present before 18 years of age included mentoring, parent relationship quality, school connectedness, and religious attendance. College graduation was the outcome of interest assessed when participants had a mean age of 28 years. Analysis was stratified by presence of COCI. About 2% of participants (N = 230) had 1 of 4 COCIs (cancer, diabetes, epilepsy, or heart disease). All 4 protective factors were associated with college graduation for youth without COCI. In the final multivariate model, only school connectedness was associated with college graduation for youth with COCI. School connectedness is of particular importance in promoting educational attainment for youth with COCI. © 2012, American School Health Association.

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…

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

PubMed

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

2017-12-07

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

Adult-onset nemaline myopathy in a dog presenting with persistent atrial standstill and primary hypothyroidism.

PubMed

Nakamura, R K; Russell, N J; Shelton, G D

2012-06-01

A nine-year-old neutered female mixed breed dog presented for evaluation following a five-day history of lethargy, inappetence, weakness, abdominal distension and generalised muscle atrophy. Persistent vatrial standstill with a junctional rhythm was identified on electrocardiogram. Echocardiogram identified moderate dilation of all cardiac chambers and mild thickening of the mitral and tricuspid valves. Serology was negative for Neospora caninum and Toxoplasma gondii. Permanent pacemaker implantation was performed in addition to endomyocardial and skeletal muscle biopsies. Cryosections from the biceps femoris muscle showed numerous nemaline rod bodies while endomyocardial biopsies were possibly consistent with end-stage myocarditis. Rod bodies have rarely been reported in the veterinary literature. To the authors' knowledge, this is the first report of adult-onset nemaline rod myopathy and hypothyroidism with concurrent cardiac disease in a dog. © 2012 British Small Animal Veterinary Association.

Associations between mental disorders and subsequent onset of hypertension

PubMed Central

Stein, Dan J.; Aguilar-Gaxiola, Sergio; Alonso, Jordi; Bruffaerts, Ronny; de Jonge, Peter; Liu, Zharoui; Caldas-de-Almeida, Jose Miguel; O’Neill, Siobhan; Viana, Maria Carmen; Al-Hamzawi, Ali Obaid; Angermeyer, Mattias C.; Benjet, Corina; de Graaf, Ron; Ferry, Finola; Kovess-Masfety, Viviane; Levinson, Daphna; de Girolamo, Giovanni; Florescu, Silvia; Hu, Chiyi; Kawakami, Norito; Haro, Josep Maria; Piazza, Marina; Wojtyniak, Bogdan J; Xavier, Miguel; Lim, Carmen C.W.; Kessler, Ronald C.; Scott, Kate

2013-01-01

Background Previous work has suggested significant associations between various psychological symptoms (e.g. depression, anxiety, anger, alcohol abuse) and hypertension. However, the presence and extent of associations between common mental disorders and subsequent adult onset of hypertension remains unclear. Further, there is little data available on how such associations vary by gender or over life course. Methods Data from the World Mental Health Surveys (comprising 19 countries, and 52,095 adults) were used. Survival analyses estimated associations between first onset of common mental disorders and subsequent onset of hypertension, with and without psychiatric comorbidity adjustment. Variations in the strength of associations by gender and by life course stage of onset of both the mental disorder and hypertension were investigated. Results After psychiatric comorbidity adjustment, depression, panic disorder, social phobia, specific phobia, binge eating disorder, bulimia nervosa, alcohol abuse, and drug abuse were significantly associated with subsequent diagnosis of hypertension (with ORs ranging from 1.1 to 1.6). Number of lifetime mental disorders was associated with subsequent hypertension in a dose-response fashion. For social phobia and alcohol abuse, associations with hypertension were stronger for males than females. For panic disorder, the association with hypertension was particularly apparent in earlier onset hypertension. Conclusions Depression, anxiety, impulsive eating disorders, and substance use disorders disorders were significantly associated with the subsequent diagnosis of hypertension. These data underscore the importance of early detection of mental disorders, and of physical health monitoring in people with these conditions.. PMID:24342112

[Rapid sequence induction in a patient with Steinert myotonic dystrophy: Interest of the association of high doses of rocuronium and sugammadex].

PubMed

Pellegrini, L; Mercier, M-F; Cornese, A; Blasco, V; Albanèse, J

2012-02-01

We report in this clinical case the successful use of a combination of rocuronium and sugammadex in a patient with Steinert myotonic dystrophy to perform a rapid sequence induction of anaesthesia. The patient had both contraindication to succinylcholine and a risk of prolonged neuromuscular blockade with non-depolarizing neuromuscular blocking agents. The use of high dose rocuronium (1mg/kg) allowed a quick and easy orotracheal intubation but induced a prolonged neuromuscular block, reversed with success by sugammadex (8 mg/kg). Copyright © 2011 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

Somatic expansion behaviour of the (CTG)n repeat in myotonic dystrophy knock-in mice is differentially affected by Msh3 and Msh6 mismatch-repair proteins.

PubMed

van den Broek, Walther J A A; Nelen, Marcel R; Wansink, Derick G; Coerwinkel, Marga M; te Riele, Hein; Groenen, Patricia J T A; Wieringa, Bé

2002-01-15

The mechanism of expansion of the (CTG)n repeat in myotonic dystrophy (DM1) patients and the cause of its pathobiological effects are still largely unknown. Most likely, long repeats exert toxicity at the level of nuclear RNA transport or splicing. Here, we analyse cis- and trans-acting parameters that determine repeat behaviour in novel mouse models for DM1. Our mice carry 'humanized' myotonic dystrophy protein kinase (Dmpk) allele(s) with either a (CTG)84 or a (CTG)11 repeat, inserted at the correct position into the endogenous DM locus. Unlike in the human situation, the (CTG)84 repeat in the syntenic mouse environment was relatively stable during intergenerational segregation. However, somatic tissues showed substantial repeat expansions which were progressive upon aging and prominent in kidney, and in stomach and small intestine, where it was cell-type restricted. Other tissues examined showed only marginal size changes. The (CTG)11 allele was completely stable, as anticipated. Introducing the (CTG)84 allele into an Msh3-deficient background completely blocked the somatic repeat instability. In contrast, Msh6 deficiency resulted in a significant increase in the frequency of somatic expansions. Competition of Msh3 and Msh6 for binding to Msh2 in functional complexes with different DNA mismatch-recognition specificity may explain why the somatic (CTG)n expansion rate is differentially affected by ablation of Msh3 and Msh6.

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

PubMed

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

2015-09-01

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

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.

Pronounced Structural and Functional Damage in Early Adult Pediatric-Onset Multiple Sclerosis with No or Minimal Clinical Disability.

PubMed

Giorgio, Antonio; Zhang, Jian; Stromillo, Maria Laura; Rossi, Francesca; Battaglini, Marco; Nichelli, Lucia; Mortilla, Marzia; Portaccio, Emilio; Hakiki, Bahia; Amato, Maria Pia; De Stefano, Nicola

2017-01-01

Pediatric-onset multiple sclerosis (POMS) may represent a model of vulnerability to damage occurring during a period of active maturation of the human brain. Whereas adaptive mechanisms seem to take place in the POMS brain in the short-medium term, natural history studies have shown that these patients reach irreversible disability, despite slower progression, at a significantly younger age than adult-onset MS (AOMS) patients. We tested for the first time whether significant brain alterations already occurred in POMS patients in their early adulthood and with no or minimal disability ( n  = 15) in comparison with age- and disability-matched AOMS patients ( n  = 14) and to normal controls (NC, n  = 20). We used a multimodal MRI approach by modeling, using FSL, voxelwise measures of microstructural integrity of white matter tracts and gray matter volumes with those of intra- and internetwork functional connectivity (FC) (analysis of variance, p  ≤ 0.01, corrected for multiple comparisons across space). POMS patients showed, when compared with both NC and AOMS patients, altered measures of diffusion tensor imaging (reduced fractional anisotropy and/or increased diffusivities) and higher probability of lesion occurrence in a clinically eloquent region for physical disability such as the posterior corona radiata. In addition, POMS patients showed, compared with the other two groups, reduced long-range FC, assessed from resting functional MRI, between default mode network and secondary visual network, whose interaction subserves important cognitive functions such as spatial attention and visual learning. Overall, this pattern of structural damage and brain connectivity disruption in early adult POMS patients with no or minimal clinical disability might explain their unfavorable clinical outcome in the long term.

Clinical profile, morbidity, and outcome of adult-onset generalized pustular psoriasis: analysis of 102 cases seen in a tertiary hospital in Johor, Malaysia.

PubMed

Choon, Siew Eng; Lai, Nai Ming; Mohammad, Norshaleyna A; Nanu, Nalini M; Tey, Kwee Eng; Chew, Shang Fern

2014-06-01

Generalized pustular psoriasis (GPP) is a severe but rare variant of psoriasis. Our objective is to review the clinical profile, comorbidities, and outcome of patients with GPP. A retrospective note review of all patients with adult-onset GPP. A total of 102 patients with adult-onset GPP were diagnosed between 1989 and November 2011, with a female to male ratio of 2 : 1. The mean age at onset of GPP was 40.9 years (range: 21-81 years). Acute GPP was the most common variant seen (95 cases), followed by four localized variants of GPP and three with annular pustular psoriasis. Fever and painful skin were present in 89% of patients, arthritis in 34.7%, and leukocytosis in 78.4%. Common triggers were systemic steroids (45 cases), pregnancy (17 cases), and upper respiratory tract infections (16 cases). A positive family history of psoriasis and GPP was present in 29% and 11%, respectively. Comorbidities included obesity (42.9%), hypertension (25.7%), hyperlipidemia (25.7%), and diabetes mellitus (23.7%). The mean duration of admission and pustular flare for acute GPP was 10.3 days (range: 3-44 days) and 16 days (range: 7-60 days), respectively. Fifty-four patients responded to systemic retinoid, 21 to methotrexate, eight to cyclosporine, and one to adalimumab, but recurrences were common. Our study confirms the poor response of GPP to currently available anti-psoriatic agents, with frequent flare-ups. There is a need for a more effective targeted therapy for this condition. © 2013 The International Society of Dermatology.

Eosinophilic myositis as first manifestation in a patient with type 2 myotonic dystrophy CCTG expansion mutation and rheumatoid arthritis.

PubMed

Meyer, Alain; Lannes, Béatrice; Carapito, Raphaël; Bahram, Seiamak; Echaniz-Laguna, Andoni; Geny, Bernard; Sibilia, Jean; Gottenberg, Jacques Eric

2015-02-01

Eosinophilic myositis is characterized by eosinophilic infiltration of skeletal muscles. In the absence of an identifiable causative factor or source (including parasitic infection, intake of drugs or L-tryptophan, certain systemic disorders as well as malignant diseases), the diagnosis of idiopathic eosinophilic myositis is usually retained. However, some muscular dystrophies have been recently identified in this subset of eosinophilic myositis. Here, we report a patient with an 8 kb CCTG expansion in intron 1 of the CNBP gene, a mutation characteristic of myotonic dystrophy type 2 (DM2), whose first manifestation was "idiopathic" eosinophilic myositis. This report suggests that in "idiopathic" eosinophilic myositis, clinicians should consider muscular dystrophies, including DM2. Copyright © 2014 Elsevier B.V. All rights reserved.

Adult Onset Still’s Disease Presenting with Acute Respiratory Distress Syndrome: Case Report and Review of the Literature

PubMed Central

Dua, Anisha B.; Manadan, Augustine M.; Case, John P.

2013-01-01

Introduction: Adult-onset Still’s disease (AOSD) is a systemic inflammatory disorder characterized by rash, leukocytosis, fevers, and arthralgias. Pulmonary involvement has been reported rarely in AOSD, but acute respiratory distress syndrome (ARDS) is extremely rare and potentially fatal and must be recognized as potential manifestation of underlying AOSD. Methods: We present a case of AOSD manifested by ARDS and review the previously reported cases in Medline/Pub med. Results: Including this case, 19 cases of AOSD complicated with ARDS have been reported in the literature. Conclusions: It is important to recognize ARDS as a manifestation of AOSD so that proper diagnostic and therapeutic management can be initiated promptly. PMID:24459537

Limbic encephalitis associated with anti-voltage-gated potassium channel complex antibodies as a cause of adult-onset mesial temporal lobe epilepsy.

PubMed

Toyota, Tomoko; Akamatsu, Naoki; Tsuji, Sadatoshi; Nishizawa, Shigeru

2014-06-01

Recently, some reports have indicated that limbic encephalitis associated with anti-voltage-gated potassium channel complex antibodies (VGKC-Ab) is a cause of adult-onset mesial temporal lobe epilepsy (MTLE). We report a 53-year-old woman who had her first epileptic seizure at the age of 50 years old. Examination by 3-Tesla brain MRI revealed left hippocampal high signal intensity and swelling on fluid-attenuated inversion recovery (FLAIR) and T2-weighted imaging at 2 months after her first seizure. The patient received intravenous methylprednisolone and carbamazepine 300 mg/day. One month later, MRI revealed improvement of her left hippocampal abnormalities. Thereafter, she had no seizures, however, three years after her first seizure, EEG revealed a seizure pattern in the left temporal region. Brain MRI revealed left hippocampal high signal intensity and brain fluorodeoxyglucose positron emission tomography revealed hypermetabolism. Her serum VGKC-Ab levels were 118 pM(normal < 100 pM). Intravenous methylprednisolone therapy was reinitiated. Two months later, her hippocampal abnormalities had improved and 3 months later her VGKC-Ab levels decreased to 4.4 pM. Remission of the epileptic seizures was also observed. This MTLE in the middle age was considered as limbic encephalitis associated with anti- VGKC-Ab. In cases of unexplained adult-onset MTLE, limbic encephalitis associated with anti-VGKC-Ab, which responds well to immunotherapy, should be considered in the differential diagnosis.

Clinical and immunological aspects and outcome of a Brazilian cohort of 414 patients with systemic lupus erythematosus (SLE): comparison between childhood-onset, adult-onset, and late-onset SLE.

PubMed

das Chagas Medeiros, M M; Bezerra, M Campos; Braga, F N Holanda Ferreira; da Justa Feijão, M R Melo; Gois, A C Rodrigues; Rebouças, V C do Rosário; de Carvalho, T M Amorim Zaranza; Carvalho, L N Solon; Ribeiro, Át Mendes

2016-04-01

The clinical expression of systemic lupus erythematosus (SLE) is influenced by genetic and environmental factors and therefore varies between ethnicities. Information on the epidemiology of SLE in Brazil is scarce and practically limited to studies conducted in socioeconomically developed regions (South and Southeast). The objective of this study was to describe the clinical and immunological aspects and outcome of a cohort of patients with SLE treated at a university hospital in northeastern Brazil and compare patterns related to age at onset: childhood (cSLE), adult (aSLE), and late (lSLE). A random sample of 414 records (women: 93.5%) were reviewed. The mean age at SLE onset and the mean disease duration were 28.9 ± 10.9 years and 10.2 ± 6.6 years, respectively. Most patients had aSLE (n = 338; 81.6%), followed by cSLE (n = 60; 14.5%) and lSLE (n = 16; 3.9%). The female/male ratio was 6.5:1 in cSLE and 16.8:1 in aSLE; in lSLE, all patients were female (p = 0.05). During follow-up, the cSLE group presented higher rates of nephritis (70% vs. 52.9% vs. 12.5%; p = 0.0001) and leuko/lymphopenia (61.7% vs. 43.8% vs. 56.2%; p = 0.02). No significant differences were found for anti-dsDNA, anti-Sm, and antiphospholipid antibodies. Treatment with immunosuppressants was significantly more common, and higher doses of prednisone were used, in cSLE. The prevalence of cardiovascular diseases were more frequent in lSLE (p = 0.03). No significant differences were found between the three groups with regard to mean damage accrual (SDI), remission, and mortality. Although cSLE presented higher rates of nephritis and leuko/lymphopenia, more frequent use of immunosuppressants and higher prednisone doses than aSLE and lSLE, the three groups did not differ significantly with regard to damage accrual, remission, and mortality. © The Author(s) 2015.

NMR Spectroscopy and Molecular Dynamics Simulation of r(CCGCUGCGG)2 Reveal a Dynamic UU Internal Loop Found in Myotonic Dystrophy Type 1†

PubMed Central

Parkesh, Raman; Fountain, Matthew; Disney, Matthew D.

2011-01-01

The NMR structure of an RNA with a copy of the 5′CUG/3′GUC motif found in the triplet repeating disorder myotonic dystrophy type 1 (DM1) is disclosed. The lowest energy conformation of the UU pair is a single hydrogen bonded structure; however, the UU protons undergo exchange indicating structural dynamics. Molecular dynamics simulations show that the single hydrogen bonded structure is the most populated one but the UU pair interconverts between 0, 1, and 2 hydrogen bonded pairs. These studies have implications for the recognition of the DM1 RNA by small molecules and proteins. PMID:21204525

Facial emotion recognition in childhood-onset bipolar I disorder: an evaluation of developmental differences between youths and adults.

PubMed

Wegbreit, Ezra; Weissman, Alexandra B; Cushman, Grace K; Puzia, Megan E; Kim, Kerri L; Leibenluft, Ellen; Dickstein, Daniel P

2015-08-01

Bipolar disorder (BD) is a severe mental illness with high healthcare costs and poor outcomes. Increasing numbers of youths are diagnosed with BD, and many adults with BD report that their symptoms started in childhood, suggesting that BD can be a developmental disorder. Studies advancing our understanding of BD have shown alterations in facial emotion recognition both in children and adults with BD compared to healthy comparison (HC) participants, but none have evaluated the development of these deficits. To address this, we examined the effect of age on facial emotion recognition in a sample that included children and adults with confirmed childhood-onset type-I BD, with the adults having been diagnosed and followed since childhood by the Course and Outcome in Bipolar Youth study. Using the Diagnostic Analysis of Non-Verbal Accuracy, we compared facial emotion recognition errors among participants with BD (n = 66; ages 7-26 years) and HC participants (n = 87; ages 7-25 years). Complementary analyses investigated errors for child and adult faces. A significant diagnosis-by-age interaction indicated that younger BD participants performed worse than expected relative to HC participants their own age. The deficits occurred both for child and adult faces and were particularly strong for angry child faces, which were most often mistaken as sad. Our results were not influenced by medications, comorbidities/substance use, or mood state/global functioning. Younger individuals with BD are worse than their peers at this important social skill. This deficit may be an important developmentally salient treatment target - that is, for cognitive remediation to improve BD youths' emotion recognition abilities. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Unusual early-onset Huntingtons disease.

PubMed

Vargas, Antonio P; Carod-Artal, Francisco J; Bomfim, Denise; Vázquez-Cabrera, Carolina; Dantas-Barbosa, Carmela

2003-06-01

Huntington's disease is an autosomal dominant progressive neurodegenerative disorder characterized by involuntary movements, cognitive decline, and behavioral disorders leading to functional disability. In contrast to patients with adult onset, in which chorea is the major motor abnormality, children often present with spasticity, rigidity, and significant intellectual decline associated with a more rapidly progressive course. An unusual early-onset Huntington's disease case of an 11-year-old boy with severe hypokinetic/rigid syndrome appearing at the age of 2.5 years is presented. Clinical diagnosis was confirmed by polymerase chain reaction study of the expanded IT-15 allele with a compatible size of 102 cytosine-adenosine-guanosine repeats L-Dopa mildly ameliorated rigidity, bradykinesia, and dystonia. We conclude that Huntington's disease should be included in the differential diagnoses of regressive syndromes of early childhood.

Refractory Genital HPV Infection and Adult-Onset Still Disease: A Case Report and Literature Review.

PubMed

Yu, Xin; Zheng, Heyi

2016-04-01

Adult-onset Still disease (AOSD) is a systemic autoimmune disease (AIID) that can develop after exposure to infectious agents. Genital human papillomavirus (HPV) infection has been reported to induce or exacerbate AIIDs, such as systemic lupus erythematosus (SLE). No guidelines are available for the management of genital warts in AOSD. Case report and literature review. We report a patient who was diagnosed AOSD in the setting of refractory and recurrent genital HPV infection, demonstrating a possible link between HPV infection and AOSD. In addition, we also discuss the management of genital warts in patients with AOSD. To the best of our knowledge, no previous cases of AOSD with genital HPV infection have been reported in literature. We then conclude that the patient AOSD may be triggered by primary HPV infection. Larger number of patient samples is needed to confirm whether HPV could trigger AOSD.

Early onset marijuana use is associated with learning inefficiencies.

PubMed

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

2016-05-01

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

Childhood and adolescent predictors of late onset criminal careers.

PubMed

Zara, Georgia; Farrington, David P

2009-03-01

This study explores the emergence of a criminal career in adulthood. The main hypothesis tested is that late criminal onset (at age 21 or later) is influenced by early factors that delay antisocial manifestations. The Cambridge Study in Delinquent Development (CSDD) was used to examine early determinants of criminal behavior. 400 Inner London males were followed from ages 8-10 to 48-50, and were classified as follows: 35 late onsetters who were first convicted at age 21 or later, and did not have high self-reported delinquency at ages 10-14 and 15-18; 129 early onsetters first convicted between ages 10 and 20; and 236 unconvicted males. Odds ratios and logistic regression analyses revealed that the best predictors of late onset offenders compared with early onset offenders included nervousness, having few friends at ages 8-10, and not having sexual intercourse by age 18. The best predictors of late onset offenders compared with nonoffenders included teacher-rated anxiousness at ages 12-14 and high neuroticism at age 16. It is concluded that being nervous and withdrawn protected boys against offending in adolescence but that these protective effects tended to wear off after age 21. These findings show that adult offending can be predicted from childhood, and suggest that early intervention might prevent a variety of maladjustment problems and difficulties in adult life.

A search for the primary abnormality in adult-onset type II citrullinemia.

PubMed

Kobayashi, K; Shaheen, N; Kumashiro, R; Tanikawa, K; O'Brien, W E; Beaudet, A L; Saheki, T

1993-11-01

Deficiency of argininosuccinate synthetase (ASS) causes citrullinemia in human beings. Type II citrullinemia is found in most patients with adult-onset citrullinemia in Japan, and ASS deficiency is found specifically in the liver. Previous studies have shown that the decrease of hepatic ASS activity is caused by a decrease in enzyme protein with normal kinetic properties and that there were no apparent abnormalities in the amount, translational activity, and gross structure of hepatic ASS mRNA. In the present work, we show by sequencing analysis that there was no mutation in the ASS mRNA from two patients with type II citrullinemia. We also report RFLP analysis of a consanguineous family with type II citrullinemia, by using three DNA polymorphisms located within the ASS gene locus. In spite of having consanguineous parents, the patient was not a homozygous haplotype for the ASS gene. The RFLP analysis of 16 affected patients from consanguineous parents showed that 5 of 16 patients had the heterozygous pattern for one of the three DNA probes and that the frequency of the heterozygous haplotype was not different from the control frequency. These results suggest that the primary defect of type II citrullinemia is not within the ASS gene locus.

A case of adult onset Still's disease complicated with cryptogenic organizing pneumonia.

PubMed

Sato, Hiroshi; Yokoe, Isamu; Nishio, Shinya; Onishi, Tsubasa; Takao, Tadashi; Kobayashi, Yasuyuki; Haraoka, Hitomi

2011-01-01

Only a few pathologic reports exist describing adult onset Still's disease (AOSD) with pulmonary involvement. We report this very rare case of AOSD complicated with cryptogenic organizing pneumonia (COP). A 32-year-old woman was referred with high spiking fever, salmon-pink rash in her arms and legs, and polyarthralgia. The laboratory data showed marked increases in white blood cell count, an erythrocyte sedimentation rate, and C reactive protein, ferritin, and liver dysfunction. All cultures remained negative, as were autoantibodies and rheumatoid factor. The patient was strongly suspected of AOSD according to specific diagnostic criteria. However, chest X ray disclosed an infiltrative shadow accompanied by air bronchogram in the upper lobe of the right lung and therapy with antibiotics was initiated. As the patient did not respond to antibiotics and a remittent fever of over 38°C, a flexible bronchoscopy was performed. Organizing pneumonia was diagnosed by transbronchial lung biopsy (TBLB) histology and radiologically, and the lesions were thought to be due to pulmonary involvement of AOSD. Therefore, she was diagnosed with AOSD complicated with COP. Oral treatment with prednisolone (30 mg/day) resulted in rapid disappearance of the infiltrative shadow. Symptoms and markers of inflammation also improved. Clinicians should be aware that COP can be a complication of AOSD.

Understanding Tobacco Use Onset Among African Americans

PubMed Central

Colby, Suzanne M.; Lu, Bo; Ferketich, Amy K.

2016-01-01

Introduction: Compared to the majority of non-Hispanic white (“white”) cigarette smokers, many African American smokers demonstrate a later age of initiation. The goal of the present study was to examine African American late-onset smoking (ie, regular smoking beginning at age 18 or later) and determine whether late-onset (vs. early-onset) smoking is protective in terms of quit rates and health outcomes. Methods: We used data from the National Survey of Midlife Development in the United States (MIDUS) because the wide age range of participants (20–75 at baseline) allowed the examination of smoking cessation and mortality incidence across the lifespan. Results: Consistent with previous research, results indicated a later average age of smoking onset among African Americans, compared to whites. Disentangling effects of race from age-of-onset, we found that the cessation rate among late-onset African American smokers was 33%, whereas rates for early-onset African American smokers and early- and late-onset white smokers ranged from 52% to 57%. Finally, results showed that among white, low-socioeconomic status (SES) smokers, the hazard rate for mortality was greater among early- versus late-onset smokers; in contrast, among African American smokers (both low- and high-SES) hazard rates for mortality did not significantly differ among early- versus late-onset smokers. Conclusions: Although late (vs. early) smoking onset may be protective for whites, the present results suggest that late-onset may not be similarly protective for African Americans. Tobacco programs and regulatory policies focused on prevention should expand their perspective to include later ages of initiation, in order to avoid widening tobacco-related health disparities. Implications: This study indicates that late-onset smoking is not only the norm among African American adult smokers, but that late- versus early-onset smoking (ie, delaying onset) does not appear to afford any benefits for African

Departure from the onset-onset rule.

PubMed

Chow, S L

1994-09-01

Using a signal-detection task, the generality of Turvey's (1973) onset-onset rule was tested in our experiments. After seeing, in succession, (1) one or two letters (target display), (2) a multiletter detection display, and (3) a mask display, subjects decided whether or not the letter or letters in the target display reappeared in the succeeding detection display at different levels of detection-display duration in various situations. The subjects' sensitivity was inconsistent with the onset-onset rule. More specifically, sensitivity increased with increases in display duration within a fixed stimulus onset asynchrony of 150 msec. Display duration, however, had no effect on response bias. Nor was there any interaction between display duration and display size in terms of either sensitivity or response bias. The more complicated relationship between display duration and display size does not invalidate the departure from the onset-onset rule.

Maternal exposure to di(2-ethylhexyl)phthalate (DEHP) promotes the transgenerational inheritance of adult-onset reproductive dysfunctions through the female germline in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pocar, Paola, E-mail: paola.pocar@unimi.it; Fianda

Endocrine disruptors (EDs) are compounds known to promote transgenerational inheritance of adult-onset disease in subsequent generations after maternal exposure during fetal gonadal development. This study was designed to establish whether gestational and lactational exposure to the plasticizer di(2-ethylhexyl)phthalate (DEHP) at environmental doses promotes transgenerational effects on reproductive health in female offspring, as adults, over three generations in the mouse. Gestating F0 mouse dams were exposed to 0, 0.05, 5 mg/kg/day DEHP in the diet from gestational day 0.5 until the end of lactation. The incidence of adult-onset disease in reproductive function was recorded in F1, F2 and F3 female offspring.more » In adult F1 females, DEHP exposure induced reproductive adverse effects with: i) altered ovarian follicular dynamics with reduced primordial follicular reserve and a larger growing pre-antral follicle population, suggesting accelerated follicular recruitment; ii) reduced oocyte quality and embryonic developmental competence; iii) dysregulation of the expression profile of a panel of selected ovarian and pre-implantation embryonic genes. F2 and F3 female offspring displayed the same altered reproductive morphological phenotype and gene expression profiles as F1, thus showing transgenerational transmission of reproductive adverse effects along the female lineage. These findings indicate that in mice exposure to DEHP at doses relevant to human exposure during gonadal sex determination significantly perturbs the reproductive indices of female adult offspring and subsequent generations. Evidence of transgenerational transmission has important implications for the reproductive health and fertility of animals and humans, significantly increasing the potential biohazards of this toxicant. - Highlights: • Maternal exposure to DEHP transgenerationally affects female reproductive health. • DEHP reduced ovarian follicular reserve up to the third generation. �

Stanford Chronic Disease Self-Management Program in myotonic dystrophy: New opportunities for occupational therapists: Stanford Chronic Disease Self-Management Program dans la dystrophie myotonique : De nouvelles opportunités pour les ergothérapeutes.

PubMed

Raymond, Kateri; Levasseur, Mélanie; Chouinard, Maud-Christine; Mathieu, Jean; Gagnon, Cynthia

2016-06-01

Chronic disease self-management is a priority in health care. Personal and environmental barriers for populations with neuromuscular disorders might diminish the efficacy of self-management programs, although they have been shown to be an effective intervention in many populations. Owing to their occupational expertise, occupational therapists might optimize self-management program interventions. This study aimed to adapt the Stanford Chronic Disease Self-Management Program (CDSMP) for people with myotonic dystrophy type 1 (DM1) and assess its acceptability and feasibility in this population. Using an adapted version of the Stanford CDSMP, a descriptive pilot study was conducted with 10 participants (five adults with DM1 and their caregivers). A semi-structured interview and questionnaires were used. The Stanford CDSMP is acceptable and feasible for individuals with DM1. However, improvements are required, such as the involvement of occupational therapists to help foster concrete utilization of self-management strategies into day-to-day tasks using their expertise in enabling occupation. Although adaptations are needed, the Stanford CDSMP remains a relevant intervention with populations requiring the application of self-management strategies. © CAOT 2016.

An additive effect of leading role in the organization between social participation and dementia onset among Japanese older adults: the AGES cohort study.

PubMed

Nemoto, Yuta; Saito, Tami; Kanamori, Satoru; Tsuji, Taishi; Shirai, Kokoro; Kikuchi, Hiroyuki; Maruo, Kazushi; Arao, Takashi; Kondo, Katsunori

2017-12-29

Several previous studies reported social participation may reduce the incident of dementia; therefore, the type of positions held in the organization may relate to dementia onset. However, this hypothesis remains largely unknown. The purpose of the present study was to examine the additive effect of a leadership position in the organization on dementia onset and social participation among elderly people in a local community, according to data from a Japanese older adults cohort study. Of 29,374 community-dwelling elderly, a total of 15,313 subjects responded to the baseline survey and were followed-up from November 2003 to March 2013. To evaluate the association between dementia onset and social participation as well as the role in the organization, we conducted Cox proportional hazard regression analysis with multiple imputation by age group (aged 75 years older or younger). The dependent variable was dementia onset, which was obtained from long-term care insurance data in Japan; independent variables were social participation and the role in the organization to which they belonged (head, manager, or treasurer). Covariates were sex, age, educational level, marriage status, job status, residence status, alcohol consumption, smoking status, and walking time, instrumental activities of daily living, depression, and medical history. During the follow-up period, 708 young-old elderly people (7.7%) and 1289 old-old elderly people (27.9%) developed dementia. In young-old elderly, relative to social non-participants, adjusted Hazard Ratio (HR) for dementia onset for participants (regular members + leadership positions) was 0.75 (95% confidence interval (CI), 0.64-0.88). Relative to regular members, adjusted HR for dementia onset for non-participants was 1.22 (95% CI, 1.02-1.46), for leadership positions 0.81 (95% CI, 0.65-0.99). The results for old-old elderly participants did not show that any significantly adjusted HR between dementia onset and social participation

Childhood-Onset Essential Hypertension and the Family Structure.

PubMed

Gupta-Malhotra, Monesha; Hashmi, Syed Shahrukh; Barratt, Michelle S; Milewicz, Dianna M; Shete, Sanjay

2016-05-01

The prevalence and effect of single-parent families in childhood-onset essential hypertension (EH) is unknown. Children with EH and age-, sex-, and ethnicity-matched controls were enrolled. Family structure data were obtained by in-person interview. A total of 148 families (76 hypertension probands, 72 control probands; median 14 years) were prospective-ly enrolled in the study. Single-parent status was seen in 42% of the families--with and without EH (38% vs 46%, P=.41; odds ratio, 0.7; 95% confidence interval, 0.4-1.4). After multivariable analysis, a statistically significant sociofamilial contributor to the development of childhood-onset EH was not identified. A significant number of single-parent families (42%), the majority with single mothers, were found in our pedigree study. Sociofamilial factors are known to contribute to the expression of adult-onset EH, but findings in our study suggest that they appear to contribute less in the expression of childhood-onset EH. ©2015 Wiley Periodicals, Inc.

Childhood/adult-onset lysosomal acid lipase deficiency: A serious metabolic and vascular phenotype beyond liver disease-four new pediatric cases.

PubMed

Poinsot, Pierre; Collardeau Frachon, Sophie; Restier, Lioara; Sérusclat, André; Di Filippo, Mathilde; Charrière, Sybil; Moulin, Philippe; Lachaux, Alain; Peretti, Noel

The childhood/adult-onset lysosomal acid lipase deficiency (LALD; late-onset LALD) is a rare genetic disease. Children present severe fatty liver disease with early cirrhosis. Before enzyme replacement therapy, statins were the standard treatment to improve the severe dyslipidemia. However, late-onset LALD should be considered as a systemic metabolic disease: chronic hyper-low-density lipoprotein and hypo-high-density lipoprotein cholesterolemia induces early atherosclerosis in addition to the liver morbidity. To assess 4 new pediatric cases of late-onset LALD with an evaluation of hepatic, metabolic, and vascular evolution under statin. Four patients were retrospectively described. Anthropometric data (weight, height, and body mass index) and laboratory data (LIPA mutations, acid lipase residual activity, liver and lipid profile, and homeostatic model assessment index) were collected. Liver histology was assessed by the noninvasive tests FibroScan and FibroTest and confirmed by liver biopsy. Vascular impact was followed up by carotid intima-media thickness (cIMT) assessment. The 4 cases of late-onset LALD came from 2 families, each with a boy (aged 8.6 and 11 years at diagnosis) and a girl (aged 10.6 and 13 years at diagnosis). Treatment with statins was performed for 8 and 5 years, respectively, from diagnosis. Statins decreased the low-density lipoprotein cholesterol mean value of 40%. All children showed significant liver fibrosis (F3 [n = 3]; F2 [n = 1]). cIMT showed the following for all children: abnormal measures without improvement and atherosclerotic plaques. One child developed a deleterious metabolic phenotype with obesity and insulin resistance (homeostatic model assessment = 3.08) associated with higher mean hepatic transaminases (149 vs 98, 88, and 61 IU/L) and increased mean cIMT values (raising from 0.47 to 0.5 mm vs 0.43 and 0.43 mm). Late-onset LALD is a rare metabolic disease with a larger impact than liver disease. Our work shows the

New-onset diabetes mellitus developing in Asian adult living donor liver transplant recipients: a single-center experience.

PubMed

Harada, Nobuhiro; Sugawara, Yasuhiko; Akamatsu, Nobuhisa; Kaneko, Junichi; Tamura, Sumihito; Aoki, Taku; Sakamoto, Yoshihiro; Hasegawa, Kiyoshi; Yamashiki, Noriyo; Kokudo, Norihiro

2013-08-01

New-onset diabetes mellitus (NODM) after liver transplantation is a common complication with a potentially negative impact on patient outcome. To evaluate the incidence of NODM and its impact on Asian adult living donor liver transplant (LDLT) recipients, we investigated 369 adult LDLT cases in our institute. Preoperative diabetes mellitus (DM) was diagnosed in 38 (9 %) patients. NODM was observed in 128/331 (38 %) patients, 56 (44 %) with persistent NODM and 72 (56 %) with transient NODM. The mean interval between LDLT and the development of NODM was 0.6 ± 1.8 (range 0-1.4) months. Multivariate analyssis revealed that older age, being male and having a higher body mass index were independent risk factors among recipients for developing NODM, while hepatitis C virus infection was not a significant risk factor, and DM had no impact on patient outcome. Although the long-term effect of DM on outcome remains to be investigated, the presence of DM after liver transplant, whether it was NODM or preexisting DM, had no impact on LDLT recipients' outcomes in mid-term. © 2013 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Low prevalence of juvenile-onset Behcet's disease with uveitis in East/South Asian people.

PubMed

Kitaichi, N; Miyazaki, A; Stanford, M R; Iwata, D; Chams, H; Ohno, S

2009-11-01

There is little information on the demographic and clinical characteristics of Behçet's disease in children in different parts of the world. We sought to provide this information through a questionnaire survey of specialist eye centres. Descriptive questionnaires were collected from 25 eye centres in 14 countries. The questionnaire surveyed details of juvenile-onset Behçet's disease with uveitis. Ethnic groups, clinical features, treatments and prognosis of paediatric-age Behçet's disease were examined on a worldwide scale. The clinical data of 135 juvenile-onset and 1227 adult-onset patients with uveitis were collected. The average age of disease diagnosis in the children was 11.7 years old. Of the ethnic groups identified 54% were from Middle East, 43% from Europe, but only 2% from East/South Asian countries. By contrast, 19.2% of adult patients were from East or South Asia. The frequency of genital ulcers in juvenile patients was 38.7%, which was significantly lower than in adult cases (53.5%; p<0.01). Behçet's disease with uveitis was less common in children than in adults in East/South Asia. Although the clinical features of the systemic disease were similar in children and adults, there was a lower frequency of genital ulceration in children.

Automated segmentation reveals silent radiographic progression in adult-onset vanishing white-matter disease.

PubMed

Huber, Thomas; Herwerth, Marina; Alberts, Esther; Kirschke, Jan S; Zimmer, Claus; Ilg, Ruediger

2017-02-01

Adult-onset vanishing white-matter disease (VWM) is a rare autosomal recessive disease with neurological symptoms such as ataxia and paraparesis, showing extensive white-matter hyperintensities (WMH) on magnetic resonance (MR) imaging. Besides symptom-specific scores like the International Cooperative Ataxia Rating Scale (ICARS), there is no established tool to monitor disease progression. Because of extensive WMH, visual comparison of MR images is challenging. Here, we report the results of an automated method of segmentation to detect alterations in T2-weighted fluid-attenuated-inversion-recovery (FLAIR) sequences in a one-year follow-up study of a clinically stable patient with genetically diagnosed VWM. Signal alterations in MR imaging were quantified with a recently published WMH segmentation method by means of extreme value distribution (EVD). Our analysis revealed progressive FLAIR alterations of 5.84% in the course of one year, whereas no significant WMH change could be detected in a stable multiple sclerosis (MS) control group. This result demonstrates that automated EVD-based segmentation allows a precise and rapid quantification of extensive FLAIR alterations like in VWM and might be a powerful tool for the clinical and scientific monitoring of degenerative white-matter diseases and potential therapeutic interventions.

Becoming disabled: The association between disability onset in younger adults and subsequent changes in productive engagement, social support, financial hardship and subjective wellbeing.

PubMed

Emerson, Eric; Kariuki, Maina; Honey, Anne; Llewellyn, Gwynnyth

2014-10-01

Very few population-based studies have investigated the association between the onset of health conditions/impairments associated with disability and subsequent well-being. To examine the association between the onset of disability and four indicators of well-being (full-time engagement in employment or education, financial hardship, social support, subjective well-being) among a nationally representative sample of Australian adolescents and young adults. Secondary analysis of the first eight waves (2001-2008) of the survey of Household Income and Labour Dynamics in Australia. For financial hardship and subjective well-being, the majority of participants belonged to trajectory classes for which there was no evidence that the onset of disability was associated with a subsequent lowering of well-being. For participation in employment and education, the majority of participants belonged to trajectory classes for which there was evidence of a modest immediate reduction in participation rates followed by subsequent stability. For social support, the majority of participants belonged to trajectory classes for which there was evidence of a modest temporary reduction in support followed by rebound back to initial levels. Membership of classes associated with poorer outcomes was associated with a number of covariates including: male gender; younger age of disability onset; being born overseas; not living with both parents at age 14; lower proficiency in the English language; and parental education being year 12 or below. The results of our analyses illustrate the existence of clear empirically defined trajectory classes following the onset of disability across a range of indicators of well-being. Copyright © 2014 Elsevier Inc. All rights reserved.

Neuropathological Comparison of Adult Onset and Juvenile Huntington's Disease with Cerebellar Atrophy: A Report of a Father and Son.

PubMed

Latimer, Caitlin S; Flanagan, Margaret E; Cimino, Patrick J; Jayadev, Suman; Davis, Marie; Hoffer, Zachary S; Montine, Thomas J; Gonzalez-Cuyar, Luis F; Bird, Thomas D; Keene, C Dirk

2017-01-01

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by a trinucleotide (CAG) repeat expansion in huntingtin (HTT) on chromosome 4. Anticipation can cause longer repeat expansions in children of HD patients. Juvenile Huntington's disease (JHD), defined as HD arising before age 20, accounts for 5-10% of HD cases, with cases arising in the first decade accounting for approximately 1%. Clinically, JHD differs from the predominately choreiform adult onset Huntington's disease (AOHD) with variable presentations, including symptoms such as myoclonus, seizures, Parkinsonism, and cognitive decline. The neuropathologic changes of AOHD are well characterized, but there are fewer reports that describe the neuropathology of JHD. Here we report a case of a six-year-old boy with paternally-inherited JHD caused by 169 CAG trinucleotide repeats who presented at age four with developmental delay, dysarthria, and seizures before dying at age 6. The boy's clinical presentation and neuropathological findings are directly compared to those of his father, who presented with AOHD and 54 repeats. A full autopsy was performed for the JHD case and a brain-only autopsy was performed for the AOHD case. Histochemically- and immunohistochemically-stained slides were prepared from formalin-fixed, paraffin-embedded tissue sections. Both cases had neuropathology corresponding to Vonsattel grade 3. The boy also had cerebellar atrophy with huntingtin-positive inclusions in the cerebellum, findings not present in the father. Autopsies of father and son provide a unique opportunity to compare and contrast the neuropathologic findings of juvenile and adult onset HD while also providing the first immunohistochemical evidence of cerebellar involvement in JHD. Additionally this is the first known report to include findings from peripheral tissue in a case of JHD.

Cutaneous manifestations associated with adult-onset Still's disease: important diagnostic values.

PubMed

Yamamoto, Toshiyuki

2012-08-01

Adult-onset Still's disease (AOSD) is a systemic inflammatory condition, characterized by a high spiking fever, leukocytosis with neutrophilia, arthralgia, and skin rash. Typical skin rash is an evanescent, salmon-pink erythema predominantly involving extremities, which is included as one of the diagnostic criteria; however, recent findings show that not only typical evanescent rash but also various skin lesions are associated with AOSD. The representative characteristic skin lesion among the non-classical skin rash is called persistent pruritic papules and plaques, which presents erythematous, slightly scaly papules with linear configuration on the trunk. Interestingly, persistent pruritic papules and plaques show unique histological features such as peculiar, distinctive distribution of dyskeratotic keratinocytes in the cornified layers as well as in the epidermis. Other non-classical skin lesions include urticaria. Current insights suggest that several inflammatory cytokines such as interleukin-1 (IL-1), IL-6, IL-18, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) play a pathogenic role in AOSD. In particular, IL-18 is suggested to play a crucial role in activating macrophages, favoring Th1 type cytokine production. IL-18 induces IFN-γ, IL-17, and TNF-α, which may play an important pathogenic role in AOSD. It is important to recognize the common and/or uncommon skin conditions of AOSD for early correct diagnosis. In this review, various skin lesions are introduced, and the complication with histiocytic necrotizing lymphadenitis (Kikuchi disease) is further discussed.

Late-onset Rasmussen Encephalitis: A literature appraisal.

PubMed

Dupont, Sophie; Gales, Ana; Sammey, Serge; Vidailhet, Marie; Lambrecq, Virginie

2017-08-01

Rasmussen Encephalitis (RE) is classically described as a childhood encephalopathy due to a unilateral inflammation of the cerebral cortex with a presumed immune-mediated pathophysiological basis. Unusual variant forms, including adolescent and adult-onset RE have been described but there is still a doubt whether these atypical cases correspond to classical RE patients. To review evidence, a systematic PubMed search was conducted to retrieve papers addressing late onset RE to assess (i) the positivity rate of classical childhood-onset diagnostic criteria for RE in late-onset RE, (ii) the specific clinical and radiological features that could help earlier diagnosis and therapeutic interventions, (iii) the arguments for an autoimmune pathophysiology including (iiia) the association with autoimmune markers or diseases and (iiib) the effects of immunomodulatory or immunosuppressive treatments. A total of 50 papers were considered. We identified 102 late-onset RE patients with a sex ratio of 8 women for 2 men. 67% fulfilled the consensus diagnostic criteria for RE. As compared to classical RE, the late-onset RE patients exhibited: i) more frequent focal complex partial seizures, ii) less frequent epilepsia partialis continua throughout evolution, iii) a slower evolution with a delayed occurrence of cortical deficit, iv) less cognitive deterioration and v) a better outcome. A specific association with autoimmune markers or diseases was not found. Immunomodulatory therapies, even performed in a late stage, improved late-onset RE patients in 61% of cases. This review proves that late-onset RE is a reality with specific clinical and radiological features. The good response to immunomodulatory treatments brings further arguments for an immune-regulated process. Copyright © 2017 Elsevier B.V. All rights reserved.

Predictors of response in generalized social phobia: effect of age of onset.

PubMed

Van Ameringen, Michael; Oakman, Jonathan; Mancini, Catherine; Pipe, Beth; Chung, Henry

2004-02-01

Selective serotonin reuptake inhibitors (SSRIs) are the gold standard for the pharmacological treatment of generalized social phobia (GSP). However, little is known about the predictors of response to treatment. Two hundred and four outpatients with GSP were randomized to sertraline (Zoloft) or placebo, for a 20-week double-blind study, with a flexible dose range of sertraline 50 to 200 mg/d. Response was defined as the percentage of patients with a Clinical Global Impression-Improvement scale (CGI-I) of 1 (very much improved) or 2 (much improved). Outcome analyses were conducted using regression models including treatment group as a categorical predictor and study visit as a repeated measure. Dependent measures included Marks Fear Questionnaire (MFQ), Brief Social Phobia Scale (BSPS), CGI-I, and Sheehan Disability Scale (SDS). We investigated several possible predictors of response to treatment including DSM-IV comorbidity, age, sex, age of onset of GSP, and duration of illness. Patients with later-onset (especially adult-onset) GSP tend to have a better response to treatment than those with earlier-onset GSP. This result generally appears in our analyses as a 2-way interaction, where the association with response is greatest for patients with adult-onset GSP (in contrast to those with child or adolescent onset). This finding is most robust for symptom measures, but is still apparent for the Sheehan measure of disability at work. This advantage for later-onset GSP can be accounted for neither by severity of illness nor by duration of illness. Superior treatment outcome for later-onset GSP may be mediated by the degree of social and family disability.

Targeting DMPK with Antisense Oligonucleotide Improves Muscle Strength in Myotonic Dystrophy Type 1 Mice.

PubMed

Jauvin, Dominic; Chrétien, Jessina; Pandey, Sanjay K; Martineau, Laurie; Revillod, Lucille; Bassez, Guillaume; Lachon, Aline; MacLeod, A Robert; Gourdon, Geneviève; Wheeler, Thurman M; Thornton, Charles A; Bennett, C Frank; Puymirat, Jack

2017-06-16

Myotonic dystrophy type 1 (DM1), a dominant hereditary muscular dystrophy, is caused by an abnormal expansion of a (CTG) n trinucleotide repeat in the 3' UTR of the human dystrophia myotonica protein kinase (DMPK) gene. As a consequence, mutant transcripts containing expanded CUG repeats are retained in nuclear foci and alter the function of splicing regulatory factors members of the MBNL and CELF families, resulting in alternative splicing misregulation of specific transcripts in affected DM1 tissues. In the present study, we treated DMSXL mice systemically with a 2'-4'-constrained, ethyl-modified (ISIS 486178) antisense oligonucleotide (ASO) targeted to the 3' UTR of the DMPK gene, which led to a 70% reduction in CUG exp RNA abundance and foci in different skeletal muscles and a 30% reduction in the heart. Furthermore, treatment with ISIS 486178 ASO improved body weight, muscle strength, and muscle histology, whereas no overt toxicity was detected. This is evidence that the reduction of CUG exp RNA improves muscle strength in DM1, suggesting that muscle weakness in DM1 patients may be improved following elimination of toxic RNAs. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Swallowing assessment in myotonic dystrophy type 1 using fiberoptic endoscopic evaluation of swallowing (FEES).

PubMed

Pilz, Walmari; Baijens, Laura W J; Passos, Valéria Lima; Verdonschot, Rob; Wesseling, Frederik; Roodenburg, Nel; Faber, Catharina G; Kremer, Bernd

2014-12-01

This study describes the swallowing function of patients with myotonic dystrophy type 1 (DM1) and the effect of bolus consistency on swallowing in this group. The aim of the study is twofold: (a) to identify which (and to what extent) swallowing variables change for DM1 patients relative to healthy control subjects and (b) to examine whether the degree of oropharyngeal dysphagia is associated with disease severity. Forty-five consecutive DM1 patients and ten healthy subjects underwent a swallowing assessment, at Maastricht University medical Center in the Netherlands. The assessment included a standardized fiberoptic endoscopic evaluation of swallowing (FEES) protocol using different bolus consistencies. Clinical severity of the disease was assessed using the muscular impairment rating scale (MIRS). Significant differences were found between patients and controls for all FEES variables. The magnitude of these differences depended on the bolus consistency. The odds of a more pathological swallowing outcome increased significantly with higher MIRS levels. In conclusion, swallowing function is found to be significantly altered in DM1 patients. The results emphasize the importance of conducting a detailed swallowing assessment in all patients, even those with mild muscle weakness. Copyright © 2014 Elsevier B.V. All rights reserved.

Understanding Tobacco Use Onset Among African Americans.

PubMed

Roberts, Megan E; Colby, Suzanne M; Lu, Bo; Ferketich, Amy K

2016-04-01

Compared to the majority of non-Hispanic white ("white") cigarette smokers, many African American smokers demonstrate a later age of initiation. The goal of the present study was to examine African American late-onset smoking (ie, regular smoking beginning at age 18 or later) and determine whether late-onset (vs. early-onset) smoking is protective in terms of quit rates and health outcomes. We used data from the National Survey of Midlife Development in the United States (MIDUS) because the wide age range of participants (20-75 at baseline) allowed the examination of smoking cessation and mortality incidence across the lifespan. Consistent with previous research, results indicated a later average age of smoking onset among African Americans, compared to whites. Disentangling effects of race from age-of-onset, we found that the cessation rate among late-onset African American smokers was 33%, whereas rates for early-onset African American smokers and early- and late-onset white smokers ranged from 52% to 57%. Finally, results showed that among white, low-socioeconomic status (SES) smokers, the hazard rate for mortality was greater among early- versus late-onset smokers; in contrast, among African American smokers (both low- and high-SES) hazard rates for mortality did not significantly differ among early- versus late-onset smokers. Although late (vs. early) smoking onset may be protective for whites, the present results suggest that late-onset may not be similarly protective for African Americans. Tobacco programs and regulatory policies focused on prevention should expand their perspective to include later ages of initiation, in order to avoid widening tobacco-related health disparities. This study indicates that late-onset smoking is not only the norm among African American adult smokers, but that late- versus early-onset smoking (ie, delaying onset) does not appear to afford any benefits for African Americans in terms of cessation or mortality. These results

The synaptic maintenance problem: membrane recycling, Ca2+ homeostasis and late onset degeneration

PubMed Central

2013-01-01

Most neurons are born with the potential to live for the entire lifespan of the organism. In addition, neurons are highly polarized cells with often long axons, extensively branched dendritic trees and many synaptic contacts. Longevity together with morphological complexity results in a formidable challenge to maintain synapses healthy and functional. This challenge is often evoked to explain adult-onset degeneration in numerous neurodegenerative disorders that result from otherwise divergent causes. However, comparably little is known about the basic cell biological mechanisms that keep normal synapses alive and functional in the first place. How the basic maintenance mechanisms are related to slow adult-onset degeneration in different diseasesis largely unclear. In this review we focus on two basic and interconnected cell biological mechanisms that are required for synaptic maintenance: endomembrane recycling and calcium (Ca2+) homeostasis. We propose that subtle defects in these homeostatic processes can lead to late onset synaptic degeneration. Moreover, the same basic mechanisms are hijacked, impaired or overstimulated in numerous neurodegenerative disorders. Understanding the pathogenesis of these disorders requires an understanding of both the initial cause of the disease and the on-going changes in basic maintenance mechanisms. Here we discuss the mechanisms that keep synapses functional over long periods of time with the emphasis on their role in slow adult-onset neurodegeneration. PMID:23829673

Late-Onset ADHD: Understanding the Evidence and Building Theoretical Frameworks.

PubMed

Caye, Arthur; Sibley, Margaret H; Swanson, James M; Rohde, Luis Augusto

2017-11-13

The traditional definition of Attention-Deficit/Hyperactivity Disorder (ADHD), assuming onset in childhood, has been challenged by evidence from four recent birth-cohort studies that reported most adults with ADHD lacked a childhood categorical ADHD diagnosis. Late onset of symptoms was evaluated in the long-term follow-up of the Multimodal Treatment study of ADHD (MTA). In most cases, other factors were present that discounted the late onset of ADHD symptoms and excluded the diagnosis of ADHD. We offer two theoretical frameworks for understanding the ADHD trajectory throughout the life cycle: (1) the complex phenotype model, and (2) the restricted phenotype model. We conclude that (a) late onset (after age 12) is a valid trajectory for ADHD symptoms, (b) the percentage of these cases with onset after adolescence is yet uncertain, and (c) the percentage meeting exclusion criteria for diagnosis of ADHD is influenced by the rigor of the methodology used to obtain evidence and whether or not DSM exclusionary criteria are applied.

Timing of Reflexive Visuospatial Orienting in Young, Young-Old, and Old-Old Adults

PubMed Central

Langley, Linda K.; Friesen, Chris Kelland; Saville, Alyson L.; Ciernia, Annie T.

2012-01-01

This study examined adult age differences in reflexive orienting to two types of uninformative spatial cues: central arrows and peripheral onsets. In two experiments using a Posner cuing task, young adults (ages 18 – 28 yrs), young-old adults (ages 60 – 74 yrs), and old-old adults (ages 75 – 92 yrs) responded to targets that were preceded 100–1,000 ms earlier by a central arrow or a peripheral abrupt onset. In Experiment 1, the cue remained present upon target onset. Facilitation effects at early cue-target stimulus onset asynchronies (SOAs) were prolonged in duration for the two older groups relative to the young adults. At later cue-target SOAs, inhibition of return (IOR) that was initiated by peripheral onset cues was observed in the performance of young adults but not in that of the two older groups. In Experiment 2, the cue was presented briefly and removed prior to target onset. The change in cue duration minimized age differences (particularly for young-old adults) in facilitation effects and led to IOR for all three age groups. The findings are consistent with the idea that attentional control settings change with age, with higher settings for older adults leading to delayed disengagement from spatial cues. PMID:21394555

Staufen1s role as a splicing factor and a disease modifier in Myotonic Dystrophy Type I

PubMed Central

Bondy-Chorney, Emma; Crawford Parks, Tara E.; Ravel-Chapuis, Aymeric; Jasmin, Bernard J.; Côté, Jocelyn

2016-01-01

ABSTRACT In a recent issue of PLOS Genetics, we reported that the double-stranded RNA-binding protein, Staufen1, functions as a disease modifier in the neuromuscular disorder Myotonic Dystrophy Type I (DM1). In this work, we demonstrated that Staufen1 regulates the alternative splicing of exon 11 of the human Insulin Receptor, a highly studied missplicing event in DM1, through Alu elements located in an intronic region. Furthermore, we found that Staufen1 overexpression regulates numerous alternative splicing events, potentially resulting in both positive and negative effects in DM1. Here, we discuss our major findings and speculate on the details of the mechanisms by which Staufen1 could regulate alternative splicing, in both normal and DM1 conditions. Finally, we highlight the importance of disease modifiers, such as Staufen1, in the DM1 pathology in order to understand the complex disease phenotype and for future development of new therapeutic strategies. PMID:27695661

Tocilizumab for uncontrollable systemic inflammatory response syndrome complicating adult-onset Still disease

PubMed Central

Masui-Ito, Asami; Okamoto, Ryuji; Ikejiri, Kaoru; Fujimoto, Mika; Tanimura, Muneyoshi; Nakamori, Shiro; Murata, Tomohiro; Ishikawa, Eiji; Yamada, Norikazu; Imai, Hiroshi; Ito, Masaaki

2017-01-01

Abstract Rationale: Adult-onset Still disease (AOSD) is a rare systemic inflammatory disease of unknown etiology characterized by evanescent salmon-pink rash, fever spikes, arthralgia, and lymphadenopathy. AOSD usually has a good prognosis, but it can sometimes be fatal, especially when it is complicated by systemic inflammatory response syndrome (SIRS) and multiple organ failure. Patient concerns: A previously healthy 26-year-old woman was referred to our hospital for persistent high fever and mild systemic edema. Five days later, the patient presented with dyspnea, hypotension, and anuria. Anasarca developed with massive pleural effusion, ascites, and systemic edema, resulting in an increase of 47 kg in body weight. Diagnoses: The patient was diagnosed as AOSD after infection, malignancy, hematologic disorders, and other autoimmune diseases were excluded. Interventions: We administered tocilizumab, an IL-6 receptor inhibitor, intravenously in addition to cyclosporine, prednisolone, plasma exchange, and continuous hemodiafiltration. Outcomes: The patient's systemic condition improved. After stabilization by all medications, the patient was managed and responded to tocilizumab alone. To the best of our knowledge, this was the first case of severe SIRS complicating AOSD that was successfully treated with an anti- IL-6 receptor antibody. Lessons: SIRS should not be overlooked in a patient with steroid-resistant AOSD and edema. Inhibitors of the IL-6 receptor can be used safely and effectively to control AOSD complicated with severe SIRS. PMID:28723802

A search for the primary abnormality in adult-onset type II citrullinemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kobayashi, Keiko; Shaheen, Nazma; Saheki, Takeyori

1993-11-01

Deficiency of argininosuccinate synthetase (ASS) causes citrullinemia in human beings. Type II citrullinemia is found in most patients with adult-onset citrullinemia in Japan, and ASS deficiency is found specifically in the liver. Previous studies have shown that the decrease of hepatic ASS activity is caused by a decrease in enzyme protein with normal kinetic properties and that there were no apparent abnormalities in the amount, translational activity, and gross structure of hepatic ASS mRNA. In the present work, the authors show by sequencing analysis that there was no mutation in the ASS mRNA from two patients with type II citrullinemia.more » The authors also report RFLP analysis of a consanguineous family with type II citrullinemia, by using three DNA polymorphisms located within the ASS gene locus. In spite of having consanguineous parents, the patient was not a homozygous haplotype for the ASS gene. The RFLP analysis of 16 affected patients from consanguineous parents showed that 5 of 16 patients had the heterozygous pattern for one of the three DNA probes and that the frequency of the heterozygous haplotype was not different from the control frequency. These results suggest that the primary defect of type II citrullinemia is not within the ASS gene locus. 29 refs., 1 fig., 3 tabs.« less

New-Onset Atrial Fibrillation in the Critically Ill*

PubMed Central

Moss, Travis J.; Calland, James Forrest; Enfield, Kyle B.; Gomez-Manjarres, Diana C.; Ruminski, Caroline; DiMarco, John P.; Lake, Douglas E.

2017-01-01

Objective: To determine the association of new-onset atrial fibrillation with outcomes, including ICU length of stay and survival. Design: Retrospective cohort of ICU admissions. We found atrial fibrillation using automated detection (≥ 90 s in 30 min) and classed as new-onset if there was no prior diagnosis of atrial fibrillation. We identified determinants of new-onset atrial fibrillation and, using propensity matching, characterized its impact on outcomes. Setting: Tertiary care academic center. Patients: A total of 8,356 consecutive adult admissions to either the medical or surgical/trauma/burn ICU with available continuous electrocardiogram data. Interventions: None. Measurements and Main Results: From 74 patient-years of every 15-minute observations, we detected atrial fibrillation in 1,610 admissions (19%), with median burden less than 2%. Most atrial fibrillation was paroxysmal; less than 2% of admissions were always in atrial fibrillation. New-onset atrial fibrillation was subclinical or went undocumented in 626, or 8% of all ICU admissions. Advanced age, acute respiratory failure, and sepsis were the strongest predictors of new-onset atrial fibrillation. In propensity-adjusted regression analyses, clinical new-onset atrial fibrillation was associated with increased hospital mortality (odds ratio, 1.63; 95% CI, 1.01–2.63) and longer length of stay (2.25 d; CI, 0.58–3.92). New-onset atrial fibrillation was not associated with survival after hospital discharge (hazard ratio, 0.99; 95% CI, 0.76–1.28 and hazard ratio, 1.11; 95% CI, 0.67–1.83, respectively, for subclinical and clinical new-onset atrial fibrillation). Conclusions: Automated analysis of continuous electrocardiogram heart rate dynamics detects new-onset atrial fibrillation in many ICU patients. Though often transient and frequently unrecognized, new-onset atrial fibrillation is associated with poor hospital outcomes. PMID:28296811

Adult-onset Alexander disease, associated with a mutation in an alternative GFAP transcript, may be phenotypically modulated by a non-neutral HDAC6 variant.

PubMed

Melchionda, Laura; Fang, Mingyan; Wang, Hairong; Fugnanesi, Valeria; Morbin, Michela; Liu, Xuanzhu; Li, Wenyan; Ceccherini, Isabella; Farina, Laura; Savoiardo, Mario; D'Adamo, Pio; Zhang, Jianguo; Costa, Alfredo; Ravaglia, Sabrina; Ghezzi, Daniele; Zeviani, Massimo

2013-05-01

We studied a family including two half-siblings, sharing the same mother, affected by slowly progressive, adult-onset neurological syndromes. In spite of the diversity of the clinical features, characterized by a mild movement disorder with cognitive impairment in the elder patient, and severe motor-neuron disease (MND) in her half-brother, the brain Magnetic Resonance Imaging (MRI) features were compatible with adult-onset Alexander's disease (AOAD), suggesting different expression of the same, genetically determined, condition. Since mutations in the alpha isoform of glial fibrillary acidic protein, GFAP-α, the only cause so far known of AOAD, were excluded, we applied exome Next Generation Sequencing (NGS) to identify gene variants, which were then functionally validated by molecular characterization of recombinant and patient-derived cells. Exome-NGS revealed a mutation in a previously neglected GFAP isoform, GFAP-ϵ, which disrupts the GFAP-associated filamentous cytoskeletal meshwork of astrocytoma cells. To shed light on the different clinical features in the two patients, we sought for variants in other genes. The male patient had a mutation, absent in his half-sister, in X-linked histone deacetylase 6, a candidate MND susceptibility gene. Exome-NGS is an unbiased approach that not only helps identify new disease genes, but may also contribute to elucidate phenotypic expression.

Tissue- and age-specific DNA replication patterns at the CTG/CAG-expanded human myotonic dystrophy type 1 locus.

PubMed

Cleary, John D; Tomé, Stéphanie; López Castel, Arturo; Panigrahi, Gagan B; Foiry, Laurent; Hagerman, Katharine A; Sroka, Hana; Chitayat, David; Gourdon, Geneviève; Pearson, Christopher E

2010-09-01

Myotonic dystrophy, caused by DM1 CTG/CAG repeat expansions, shows varying instability levels between tissues and across ages within patients. We determined DNA replication profiles at the DM1 locus in patient fibroblasts and tissues from DM1 transgenic mice of various ages showing different instability. In patient cells, the repeat is flanked by two replication origins demarcated by CTCF sites, with replication diminished at the expansion. In mice, the expansion replicated from only the downstream origin (CAG as lagging template). In testes from mice of three different ages, replication toward the repeat paused at the earliest age and was relieved at later ages-coinciding with increased instability. Brain, pancreas and thymus replication varied with CpG methylation at DM1 CTCF sites. CTCF sites between progressing forks and repeats reduced replication depending on chromatin. Thus, varying replication progression may affect tissue- and age-specific repeat instability.

The association between peer, parental influence and tobacco product features and earlier age of onset of regular smoking among adults in 27 European countries.

PubMed

Filippidis, Filippos T; Agaku, Israel T; Vardavas, Constantine I

2015-10-01

Factors that influence smoking initiation and age of smoking onset are important considerations in tobacco control. We evaluated European Union (EU)-wide differences in the age of onset of regular smoking, and the potential role of peer, parental and tobacco product design features on the earlier onset of regular smoking among adults <40 years old in 27 EU countries. We analysed data from 4442 current and former smokers aged 15-39 years, collected for the Eurobarometer 77.1 survey (2012). Respondents reported their age at regular smoking onset and factors that influenced their decision to start smoking, including peer influence, parental influence and features of tobacco products. Multi-variable logistic regression, adjusted for age; geographic region; education; difficulty to pay bills; and gender, was used to assess the role of the various pro-tobacco influences on early onset of regular smoking (i.e. <18 years). Among ever smokers, the mean age of onset of regular smoking was 16.6 years, ranging from 15.8 to 18.8 years in member countries. 68.1% responded that they started smoking regularly when they were <18 years old. Ever smokers who reported they were influenced by peers (OR = 1.70; 95%CI 1.30-2.20) or parents (OR = 1.60; 95%CI 1.21-2.12) were more likely to have started smoking regularly <18 years old. No significant association between design and marketing features of tobacco products and an early initiation of regular smoking was observed (OR = 1.04; 95%CI 0.83-1.31). We identified major differences in smoking initiation patterns among EU countries, which may warrant different approaches in the prevention of tobacco use. © The Author 2015. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Genome-wide Association for Major Depression Through Age at Onset Stratification: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.

PubMed

Power, Robert A; Tansey, Katherine E; Buttenschøn, Henriette Nørmølle; Cohen-Woods, Sarah; Bigdeli, Tim; Hall, Lynsey S; Kutalik, Zoltán; Lee, S Hong; Ripke, Stephan; Steinberg, Stacy; Teumer, Alexander; Viktorin, Alexander; Wray, Naomi R; Arolt, Volker; Baune, Bernard T; Boomsma, Dorret I; Børglum, Anders D; Byrne, Enda M; Castelao, Enrique; Craddock, Nick; Craig, Ian W; Dannlowski, Udo; Deary, Ian J; Degenhardt, Franziska; Forstner, Andreas J; Gordon, Scott D; Grabe, Hans J; Grove, Jakob; Hamilton, Steven P; Hayward, Caroline; Heath, Andrew C; Hocking, Lynne J; Homuth, Georg; Hottenga, Jouke J; Kloiber, Stefan; Krogh, Jesper; Landén, Mikael; Lang, Maren; Levinson, Douglas F; Lichtenstein, Paul; Lucae, Susanne; MacIntyre, Donald J; Madden, Pamela; Magnusson, Patrik K E; Martin, Nicholas G; McIntosh, Andrew M; Middeldorp, Christel M; Milaneschi, Yuri; Montgomery, Grant W; Mors, Ole; Müller-Myhsok, Bertram; Nyholt, Dale R; Oskarsson, Hogni; Owen, Michael J; Padmanabhan, Sandosh; Penninx, Brenda W J H; Pergadia, Michele L; Porteous, David J; Potash, James B; Preisig, Martin; Rivera, Margarita; Shi, Jianxin; Shyn, Stanley I; Sigurdsson, Engilbert; Smit, Johannes H; Smith, Blair H; Stefansson, Hreinn; Stefansson, Kari; Strohmaier, Jana; Sullivan, Patrick F; Thomson, Pippa; Thorgeirsson, Thorgeir E; Van der Auwera, Sandra; Weissman, Myrna M; Breen, Gerome; Lewis, Cathryn M

2017-02-15

Major depressive disorder (MDD) is a disabling mood disorder, and despite a known heritable component, a large meta-analysis of genome-wide association studies revealed no replicable genetic risk variants. Given prior evidence of heterogeneity by age at onset in MDD, we tested whether genome-wide significant risk variants for MDD could be identified in cases subdivided by age at onset. Discovery case-control genome-wide association studies were performed where cases were stratified using increasing/decreasing age-at-onset cutoffs; significant single nucleotide polymorphisms were tested in nine independent replication samples, giving a total sample of 22,158 cases and 133,749 control subjects for subsetting. Polygenic score analysis was used to examine whether differences in shared genetic risk exists between earlier and adult-onset MDD with commonly comorbid disorders of schizophrenia, bipolar disorder, Alzheimer's disease, and coronary artery disease. We identified one replicated genome-wide significant locus associated with adult-onset (>27 years) MDD (rs7647854, odds ratio: 1.16, 95% confidence interval: 1.11-1.21, p = 5.2 × 10 -11 ). Using polygenic score analyses, we show that earlier-onset MDD is genetically more similar to schizophrenia and bipolar disorder than adult-onset MDD. We demonstrate that using additional phenotype data previously collected by genetic studies to tackle phenotypic heterogeneity in MDD can successfully lead to the discovery of genetic risk factor despite reduced sample size. Furthermore, our results suggest that the genetic susceptibility to MDD differs between adult- and earlier-onset MDD, with earlier-onset cases having a greater genetic overlap with schizophrenia and bipolar disorder. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Age at onset in patients with medically refractory temporal lobe epilepsy and mesial temporal sclerosis: impact on clinical manifestations and postsurgical outcome.

PubMed

Asadi-Pooya, Ali A; Sperling, Michael R

2015-08-01

To evaluate the demographic and clinical manifestations and postsurgical outcome of childhood-onset mesial temporal sclerosis and temporal lobe epilepsy (MTS-TLE) and establishing the potential differences as compared to the patients with adult-onset MTS-TLE. In this retrospective study all patients with a clinical diagnosis of medically refractory TLE due to mesial temporal sclerosis, who underwent epilepsy surgery at Jefferson comprehensive epilepsy center, were recruited. Patients were prospectively registered in a database from 1986 through 2014. Postsurgical outcome was classified into two groups; seizure-free or relapsed. Clinical manifestations and outcome were compared between patients with childhood-onset MTS-TLE (i.e., age at onset of the first afebrile habitual seizure below 10 years) and those with adult-onset MTS-TLE (i.e., age at onset of the first afebrile habitual seizure 20 years or above). One hundred and twelve patients had childhood-onset MTS-TLE and 76 had adult-onset MTS-TLE. Demographic, clinical, EEG and MRI characteristics of these two groups were similar. Postoperative outcome was not statistically different between these two groups of patients (P=0.9). Temporal lobe epilepsy due to mesial temporal sclerosis is a common cause of epilepsy that can start from early childhood to late adulthood. The etiology of MTS-TLE may be different in various age groups, but it seems that when mesial temporal sclerosis is the pathological substrate of TLE, clinical manifestations and response to surgical treatment of patients are very similar in patients with childhood-onset MTS-TLE compared to those with adult-onset disease. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Longitudinal association of delta activity at sleep onset with cognitive and affective function in community-dwelling older adults.

PubMed

Kawai, Makoto; Beaudreau, Sherry A; Gould, Christine E; Hantke, Nathan C; Cotto, Isabelle; Jordan, Josh T; Hirst, Rayna B; O'Hara, Ruth

2016-10-01

This investigation sought to determine whether delta activity at sleep onset (DASO) in the sleep electroencephalography of older adults represents normal variation or is associated with clinical pathology. To this end, we examined its longitudinal associations with cognitive and affective function in older adults without dementia. Participants were 153 community-dwelling older adults without dementia. We evaluated polysomnography (PSG), cognitive performance, and affective function at four time points: baseline, 12, 24, and 36 months. All participants completed PSG and measures of global cognition, delayed verbal memory, information processing speed, attention, inhibition, verbal naming, visuospatial ability, and measures of anxiety and depression. DASO was defined as sequences of rhythmic anterior delta activity on PSG in the transition from awake to sleep during the baseline assessment (Figure ). At the baseline, 83 women and 70 men, mean age 71.3 ± 0.6 years participated and 19.6% of participants exhibited DASO. Age, years of education, gender, and body mass index did not differ according to DASO status. Linear mixed modeling showed that the presence of DASO was actually associated with lower levels of anxiety and depression. Further, participants with DASO, versus those without DASO, exhibited a trend towards better cognitive performance over time, although none of these associations reached statistical significance. Whereas DASO was associated with better affective function, no significant association was found between DASO and cognitive change over time. These longitudinal findings support the view that the presence of DASO in healthy older adults represents normal variation rather than pathological aging. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Childhood separation anxiety disorder and adult onset panic attacks share a common genetic diathesis.

PubMed

Roberson-Nay, Roxann; Eaves, Lindon J; Hettema, John M; Kendler, Kenneth S; Silberg, Judy L

2012-04-01

Childhood separation anxiety disorder (SAD) is hypothesized to share etiologic roots with panic disorder. The aim of this study was to estimate the genetic and environmental sources of covariance between childhood SAD and adult onset panic attacks (AOPA), with the primary goal to determine whether these two phenotypes share a common genetic diathesis. Participants included parents and their monozygotic or dizygotic twins (n = 1,437 twin pairs) participating in the Virginia Twin Study of Adolescent Behavioral Development and those twins who later completed the Young Adult Follow-Up (YAFU). The Child and Adolescent Psychiatric Assessment was completed at three waves during childhood/adolescence followed by the Structured Clinical Interview for DSM-III-R at the YAFU. Two separate, bivariate Cholesky models were fit to childhood diagnoses of SAD and overanxious disorder (OAD), respectively, and their relation with AOPA; a trivariate Cholesky model also examined the collective influence of childhood SAD and OAD on AOPA. In the best-fitting bivariate model, the covariation between SAD and AOPA was accounted for by genetic and unique environmental factors only, with the genetic factor associated with childhood SAD explaining significant variance in AOPA. Environmental risk factors were not significantly shared between SAD and AOPA. By contrast, the genetic factor associated with childhood OAD did not contribute significantly to AOPA. Results of the trivariate Cholesky reaffirmed outcomes of bivariate models. These data indicate that childhood SAD and AOPA share a common genetic diathesis that is not observed for childhood OAD, strongly supporting the hypothesis of a specific genetic etiologic link between the two phenotypes. © 2012 Wiley Periodicals, Inc.

[Quality of life of young adults after a growth hormone therapy with childhood onset].

PubMed

Quitmann, J H; Rohenkohl, A C; Kammerer, U; Schöfl, C; Bullinger, M; Dörr, H-G

2014-11-01

Little is known about the health-related quality of life of young adults with childhood onset idiopathic growth hormone deficiency or neurosecretory dysfunction of growth hormone secretion, who have been treated with recombinant human growth hormone (GH). Patients were diagnosed and treated with human growth hormone at the University Children´s Hospital in Erlangen (n=85). The data of both groups were merged for analysis, because no difference between idiopathic growth hormone deficiency and neurosecretory dysfunction of growth hormone secretion in auxological. Data were found. Health-related quality of life was cross- sectionally assessed after the end of growth hormone therapy with the Short Form-36 Health Survey and the Nottingham Health Profiles for which population based norm data are available. At the time of the survey, the patients (53 m, 32 f) were 23.5 ± 4.6 years old. At start of GH therapy, age was 10.5 ± 2.8 and at the end 16.3 ± 1,4 years. At start, height SDS was -3.20 ± 1.06. GH dose was 0,026 ± 0,012 mg/kg/d (daily s. c.-injections). The increase in height SDS after the end of GH therapy was 1.69 ± 1.22.  Compared to the reference population, patients reported significantly lower scores on the scales energy level, vitality, social functioning, indicating a greater social isolation, a stronger emotional reaction, an increased loss of mobility and a worse psychological state. Young adults report specific impairments after completion of GH therapy. © Georg Thieme Verlag KG Stuttgart · New York.

Induction and Reversal of Myotonic Dystrophy Type 1 Pre-mRNA Splicing Defects by Small Molecules

PubMed Central

Childs-Disney, Jessica L.; Stepniak-Konieczna, Ewa; Tran, Tuan; Yildirim, Ilyas; Park, HaJeung; Chen, Catherine Z.; Hoskins, Jason; Southall, Noel; Marugan, Juan J.; Patnaik, Samarjit; Zheng, Wei; Austin, Chris P.; Schatz, George C.; Sobczak, Krzysztof; Thornton, Charles A.; Disney, Matthew D.

2013-01-01

The ability to control pre-mRNA splicing with small molecules could facilitate the development of therapeutics or cell-based circuits that control gene function. Myotonic dystrophy type 1 (DM1) is caused by the dysregulation of alternative pre-mRNA splicing due to sequestration of muscleblind-like 1 protein (MBNL1) by expanded, non-coding r(CUG) repeats (r(CUG)exp). Here we report two small molecules that induce or ameliorate alternative splicing dysregulation. The thiophene-containing small molecule (1) inhibits the interaction of MBNL1 with its natural pre-mRNA substrates. Compound (2), a substituted naphthyridine, binds r(CUG)exp and displaces MBNL1. Structural models show that 1 binds MBNL1 in the Zn-finger domain and that 2 interacts with UU loops in r(CUG)exp. This study provides a structural framework for small molecules that target MBNL1 by mimicking r(CUG)exp and shows that targeting MBNL1 causes dysregulation of alternative splicing, suggesting that MBNL1 is thus not a suitable therapeutic target for the treatment of DM1. PMID:23806903

Mild encephalitis/encephalopathy with reversible splenial lesion (MERS) in adults-a case report and literature review.

PubMed

Yuan, Junliang; Yang, Shuna; Wang, Shuangkun; Qin, Wei; Yang, Lei; Hu, Wenli

2017-05-25

Mild encephalitis/encephalopathy with reversible splenial lesion (MERS) is a rare clinico-radiological entity characterized by the magnetic resonance imaging (MRI) finding of a reversible lesion in the corpus callosum, sometimes involved the symmetrical white matters. Many cases of child-onset MERS with various causes have been reported. However, adult-onset MERS is relatively rare. The clinical characteristics and pathophysiologiccal mechanisms of adult-onset MERS are not well understood. We reviewed the literature on adult-onset MERS in order to describe the characteristics of MERS in adults and to provide experiences for clinician. We reported a case of adult-onset MERS with acute urinary retension and performed literature search from PubMed and web of science databases to identify other adult-onset MERS reports from Januarary 2004 to March 2016. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed on selection process. And then we summarized the clinico-radiological features of adult-onset MERS. Twenty-nine adult-onset MERS cases were reviewed from available literature including the case we have. 86.2% of the cases (25/29) were reported in Asia, especially in Japan. Ages varied between 18 and 59 years old with a 12:17 female-to-male ratio. The major cause was infection by virus or bacteria. Fever and headache were the most common clinical manifestation, and acute urinary retention was observed in 6 patients. All patients recovered completely within a month. Adult-onset MERS is an entity with a broad clinico-radiological spectrum because of the various diseases and conditions. There are similar characteristics between MERS in adults and children, also some differences.

Development and Psychometric Evaluation of a Health-Related Quality of Life Instrument for Individuals with Adult-Onset Hearing Loss

PubMed Central

Stika, Carren J.; Hays, Ron D.

2016-01-01

Objective Self-reports of “hearing handicap” are available, but a comprehensive measure of health-related quality of life (HRQOL) for individuals with adult-onset hearing loss (AOHL) does not exist. Our objective was to develop and evaluate a multidimensional HRQOL instrument for individuals with AOHL. Design The Impact of Hearing Loss Inventory Tool (IHEAR-IT) was developed using results of focus groups, a literature review, Advisory Expert Panel input, and cognitive interviews. Study Sample The 73-item field-test instrument was completed by 409 adults (22-91 years old) with varying degrees of AOHL and from different areas of the US. Results Multitrait scaling analysis supported four multi-item scales and five individual items. Internal consistency reliabilities ranged from 0.93 to 0.96 for the scales. Construct validity was supported by correlations between the IHEAR-IT scales and scores on the 36-Item Short Form Health Survey, Version 2.0 (SF-36v2) Mental Composite Summary (r’s = 0.32 – 0.64) and the Hearing Handicap Inventory for the Elderly/Adults (HHIE/HHIA) (r’s > −0.70). Conclusions The field test provide initial support for the reliability and construct validity of the IHEAR-IT for evaluating HRQOL of individuals with AOHL. Further research is needed to evaluate the responsiveness to change of the IHEAR-IT scales and identify items for a short-form. PMID:27104754

Immunoglobulin G antibodies against indoor dampness-related microbes and adult-onset asthma: a population-based incident case–control study

PubMed Central

JAAKKOLA, M S; LAITINEN, S; PIIPARI, R; UITTI, J; NORDMAN, H; HAAPALA, A-M; JAAKKOLA, J J K

2002-01-01

Immunoglobulin G (IgG) antibodies against microbes related to indoor dampness problems have been used as potential biomarkers of fungal exposure in clinical investigations. There is limited information on their relation to asthma. We conducted a population-based incident case–control study to assess the risk of asthma in relation to specific IgG antibodies to eight dampness-related microbes: Aspergillus fumigatus, A. versicolor, Cladosporium cladosporioides, Fusarium oxysporum, Sporobolomyces salmonicolor, Stachybotrys chartarum, Streptomyces albus and Trichoderma citrinoviride. We recruited systematically all new cases of asthma during a 2·5-year study period and randomly selected controls from a source population of adults 21–63 years of age living in the Pirkanmaa Hospital District, South Finland. The clinically diagnosed case series consisted of 521 adults with newly diagnosed asthma and the control series of 932 controls selected randomly from the source population. IgG antibodies were analysed with ELISA. An increased risk of developing asthma in adulthood was significantly related to IgG antibodies to T. citrinoviride, but not to the other moulds. There was no evidence of a dose–response relation between the IgG antibody level and the risk of asthma. T. citrinoviride may play a role in the aetiology of adult-onset asthma or serve as an indicator of other causal factors. PMID:12100029

Development and psychometric evaluation of a health-related quality of life instrument for individuals with adult-onset hearing loss.

PubMed

Stika, Carren J; Hays, Ron D

2015-07-01

Self-reports of 'hearing handicap' are available, but a comprehensive measure of health-related quality of life (HRQOL) for individuals with adult-onset hearing loss (AOHL) does not exist. Our objective was to develop and evaluate a multidimensional HRQOL instrument for individuals with AOHL. The Impact of Hearing Loss Inventory Tool (IHEAR-IT) was developed using results of focus groups, a literature review, advisory expert panel input, and cognitive interviews. The 73-item field-test instrument was completed by 409 adults (22-91 years old) with varying degrees of AOHL and from different areas of the USA. Multitrait scaling analysis supported four multi-item scales and five individual items. Internal consistency reliabilities ranged from 0.93 to 0.96 for the scales. Construct validity was supported by correlations between the IHEAR-IT scales and scores on the 36-item Short Form Health Survey, version 2.0 (SF-36v2) mental composite summary (r = 0.32-0.64) and the Hearing Handicap Inventory for the Elderly/Adults (HHIE/HHIA) (r ≥ -0.70). The field test provides initial support for the reliability and construct validity of the IHEAR-IT for evaluating HRQOL of individuals with AOHL. Further research is needed to evaluate the responsiveness to change of the IHEAR-IT scales and identify items for a short-form.

Delayed-onset progressive movement disorders after static brain lesions.

PubMed

Scott, B L; Jankovic, J

1996-01-01

We studied 53 patients (64% females) with static brain lesions who developed progressive movement disorders. Of these, 50 (94%) had dystonia, 17 (32%) tremor, eight (15%) parkinsonism, seven (13%) myoclonus, and three (6%) chorea. The precipitating insults included perinatal hypoxia/ischemia in 22 (42%), stroke in 12 (23%), head injury in eight (15%), encephalitis in eight (15%), and carbon monoxide poisoning, kernicterus, and radiation necrosis in one patient (2%) each. Among the 30 patients with initial insult occurring at age 2 years or younger (Infant group), distribution of dystonia at follow-up was focal in three (10%), segmental in eight (27%), unilateral in 10 (33%), and generalized in nine (30%). The mean latency between the original injury and onset of movement disorder was 25.5 +/- 16.7 years. Among the nine patients who developed dystonia after an insult occurring between ages 6 and 17 (Childhood group), the distribution of dystonia at follow-up was segmental in two (33%) and unilateral in seven (78%); the mean latency of dystonia onset was 4.9 +/- 7.8 years. Of the 14 patients in the Adult group (injury at age 25 or older), 11 developed dystonia, two developed parkinsonism, and one had carbon monoxide encephalopathy and parkinsonism. The distribution of dystonia in the 11 patients at follow-up was segmental in three (27%) and unilateral in eight (73%). The mean latency of movement disorder onset in the 14 patients of the Adult group was 2.5 +/- 4.9 years. No individuals in the Childhood or Adult groups became left-hand dominant; by comparison, nine of the 30 individuals in the Infant group became left-handed. In conclusion, brain injury at a young age is associated with a longer latency to onset of subsequent movement disorder, a greater tendency to development of generalized dystonia, and a greater probability of altered handedness. These tendencies may result from differences in age-related neuroplasticity.

Depression and the Onset of Dementia in Adults with Mental Retardation.

ERIC Educational Resources Information Center

Burt, Diana Byrd; And Others

1992-01-01

Comparison of 61 adults with Down's syndrome and 43 adults with mental retardation resulting from other causes found that 8 Down's syndrome adults had both depression and declines in functioning, whereas no adults in the other group showed functional declines. Greater severity of depression was related to poor functioning in adults with Down's…

Coping efforts and resilience among adult children who grew up with a parent with young-onset dementia: a qualitative follow-up study

PubMed Central

Johannessen, Aud; Engedal, Knut; Thorsen, Kirsten

2016-01-01

Background It is estimated that one in four persons with young-onset dementia (YOD) (<65 years old) has children younger than 18 years old at the onset of the dementia. These children experience a childhood different from what is expected. Adult children of parents with YOD are seldom addressed in research, and the impact of the dementia on the children's development over time has rarely been studied. Aim The goal of this study was to explore how adult children experienced the influence of their parents’ dementia on their own development during adolescence; what coping efforts, strategies, and resources they employed; and how they evaluated the most recent changes in their life situation. Method A follow-up, grounded theory approach in two phases was used. Qualitative interviews with 14 informants (18–30 years of age) were conducted in 2014 and one year later, in 2015. Findings Nearly all the informants expressed that their emotional well-being and their life situation were better at the second interview compared to the time of dementia onset in their parents. To overcome the difficulties of being a child of a parent with YOD, they used different instrumental, cognitive, and emotional coping strategies, subsumed analytically under the concept detachment. This category covers three subcategories of coping strategies: moving apart, greater personal distance, and calmer emotional reactions. Another category, resilience, designates combinations of the coping strategies. Vital for the development of coping resources and resilience was the need the informants had for social support—for people they saw who listened to them and responded to their needs. Conclusion Most of the informants reported that they experienced a better life situation and less emotional stress over time as their parent's dementia progressed. They developed better coping capacities and greater resilience. Vital for the development of coping resources and resilience was the need the informants

Inhibition of GSK-3 Ameliorates Aβ Pathology in an Adult-Onset Drosophila Model of Alzheimer's Disease

PubMed Central

Killick, Richard; Augustin, Hrvoje; Gandy, Carina; Allen, Marcus J.; Hardy, John; Lovestone, Simon; Partridge, Linda

2010-01-01

Aβ peptide accumulation is thought to be the primary event in the pathogenesis of Alzheimer's disease (AD), with downstream neurotoxic effects including the hyperphosphorylation of tau protein. Glycogen synthase kinase-3 (GSK-3) is increasingly implicated as playing a pivotal role in this amyloid cascade. We have developed an adult-onset Drosophila model of AD, using an inducible gene expression system to express Arctic mutant Aβ42 specifically in adult neurons, to avoid developmental effects. Aβ42 accumulated with age in these flies and they displayed increased mortality together with progressive neuronal dysfunction, but in the apparent absence of neuronal loss. This fly model can thus be used to examine the role of events during adulthood and early AD aetiology. Expression of Aβ42 in adult neurons increased GSK-3 activity, and inhibition of GSK-3 (either genetically or pharmacologically by lithium treatment) rescued Aβ42 toxicity. Aβ42 pathogenesis was also reduced by removal of endogenous fly tau; but, within the limits of detection of available methods, tau phosphorylation did not appear to be altered in flies expressing Aβ42. The GSK-3–mediated effects on Aβ42 toxicity appear to be at least in part mediated by tau-independent mechanisms, because the protective effect of lithium alone was greater than that of the removal of tau alone. Finally, Aβ42 levels were reduced upon GSK-3 inhibition, pointing to a direct role of GSK-3 in the regulation of Aβ42 peptide level, in the absence of APP processing. Our study points to the need both to identify the mechanisms by which GSK-3 modulates Aβ42 levels in the fly and to determine if similar mechanisms are present in mammals, and it supports the potential therapeutic use of GSK-3 inhibitors in AD. PMID:20824130