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Sample records for adult-onset antibody deficiency

  1. Very long chain acyl-coenzyme A dehydrogenase deficiency with adult onset

    DEFF Research Database (Denmark)

    Smelt, A H; Poorthuis, B J; Onkenhout, W

    1998-01-01

    Very long chain acyl-coenzyme A (acyl-CoA) dehydrogenase (VLCAD) deficiency is a severe disorder of mitochondrial beta-oxidation in infants. We report adult onset of attacks of painful rhabdomyolysis. Gas chromatography identified strongly elevated levels of tetradecenoic acid, 14:1(n-9), tetrade......Very long chain acyl-coenzyme A (acyl-CoA) dehydrogenase (VLCAD) deficiency is a severe disorder of mitochondrial beta-oxidation in infants. We report adult onset of attacks of painful rhabdomyolysis. Gas chromatography identified strongly elevated levels of tetradecenoic acid, 14:1(n-9......), tetradecadienoic acid, 14:2(n-6), and hexadecadienoic acid, 16:2(n-6). Palmitoyl-CoA and behenoyl-CoA dehydrogenase in fibroblasts were deficient. Muscle VLCAD activity was very low. DNA analysis revealed compound heterozygosity for two missense mutations in the VLCAD gene. The relatively mild clinical course may...... be due to residual enzyme activity as a consequence of the two missense mutations. Treatment with L-carnitine and medium chain triglycerides in the diet did not reduce the attacks of rhabdomyolysis....

  2. Delayed Diagnosis and Complications of Predominantly Antibody Deficiencies in a Cohort of Australian Adults

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    Charlotte A. Slade

    2018-05-01

    Full Text Available BackgroundPredominantly antibody deficiencies (PADs are the most common type of primary immunodeficiency in adults. PADs frequently pass undetected leading to delayed diagnosis, delayed treatment, and the potential for end-organ damage including bronchiectasis. In addition, PADs are frequently accompanied by comorbid autoimmune disease, and an increased risk of malignancy.ObjectivesTo characterize the diagnostic and clinical features of adult PAD patients in Victoria, Australia.MethodsWe identified adult patients receiving, or having previously received immunoglobulin replacement therapy for a PAD at four hospitals in metropolitan Melbourne, and retrospectively characterized their clinical and diagnostic features.Results179 patients from The Royal Melbourne, Alfred and Austin Hospitals, and Monash Medical Centre were included in the study with a median age of 49.7 years (range: 16–87 years, of whom 98 (54.7% were female. The majority of patients (116; 64.8% met diagnostic criteria for common variable immunodeficiency (CVID, and 21 (11.7% were diagnosed with X-linked agammaglobulinemia (XLA. Unclassified hypogammaglobulinemia (HGG was described in 22 patients (12.3%, IgG subclass deficiency (IGSCD in 12 (6.7%, and specific antibody deficiency (SpAD in 4 individuals (2.2%. The remaining four patients had a diagnosis of Good syndrome (thymoma with immunodeficiency. There was no significant difference between the age at diagnosis of the disorders, with the exception of XLA, with a median age at diagnosis of less than 1 year. The median age of reported symptom onset was 20 years for those with a diagnosis of CVID, with a median age at diagnosis of 35 years. CVID patients experienced significantly more non-infectious complications, such as autoimmune cytopenias and lymphoproliferative disease, than the other antibody deficiency disorders. The presence of non-infectious complications was associated with significantly reduced survival in the

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

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    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

  4. Leaky RAG Deficiency in Adult Patients with Impaired Antibody Production against Bacterial Polysaccharide Antigens.

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    Christoph B Geier

    Full Text Available Loss of function mutations in the recombination activating genes RAG1 and RAG2 have been reported to cause a T-B-NK+ type of severe combined immunodeficiency. In addition identification of hypomorphic mutations in RAG1 and RAG2 has led to an expansion of the spectrum of disease to include Omenn syndrome, early onset autoimmunity, granuloma, chronic cytomegalovirus- or EBV-infection with expansion of gamma/delta T-cells, idiophatic CD4 lymphopenia and a phenotype resembling common variable immunodeficiency. Herein we describe a novel presentation of leaky RAG1 and RAG2 deficiency in two unrelated adult patients with impaired antibody production against bacterial polysaccharide antigens. Clinical manifestation included recurrent pneumonia, sinusitis, otitis media and in one patient recurrent cutaneous vasculitis. Both patients harbored a combination of a null mutation on one allele with a novel hypomorphic RAG1/2 mutation on the other allele. One of these novel mutations affected the start codon of RAG1 and resulted in an aberrant gene and protein expression. The second novel RAG2 mutation leads to a truncated RAG2 protein, lacking the C-terminus with intact core RAG2 and reduced VDJ recombination capacity as previously described in a mouse model. Both patients presented with severely decreased numbers of naïve CD4+ T cells and defective T independent IgG responses to bacterial polysaccharide antigens, while T cell-dependent IgG antibody formation e.g. after tetanus or TBEV vaccination was intact. In conclusion, hypomorphic mutations in genes responsible for SCID should be considered in adults with predominantly antibody deficiency.

  5. Growth hormone effects on cortical bone dimensions in young adults with childhood-onset growth hormone deficiency

    DEFF Research Database (Denmark)

    Hyldstrup, L; Conway, G S; Racz, K

    2012-01-01

    Growth hormone (GH) treatment in young adults with childhood-onset GH deficiency has beneficial effects on bone mass. The present study shows that cortical bone dimensions also benefit from GH treatment, with endosteal expansion and increased cortical thickness leading to improved bone strength....... INTRODUCTION: In young adults with childhood-onset growth hormone deficiency (CO GHD), GH treatment after final height is reached has been shown to have beneficial effects on spine and hip bone mineral density. The objective of the study was to evaluate the influence of GH on cortical bone dimensions. METHODS...

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

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    Geng, Hui; Carlsen, Stefan; Nandakumar, Kutty

    2008-01-01

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

  7. The impact of idiopathic childhood-onset growth hormone deficiency (GHD) on bone mass in subjects without adult GHD

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    Lange, Martin; Müller, Jørn; Svendsen, Ole Lander

    2005-01-01

    Despite seemingly adequate growth hormone (GH) treatment during childhood, children with GH deficiency (GHD) have reduced bone mineral density (BMD) at final height. The aim was to evaluate BMD and bone mineral content (BMC) in adults treated for idiopathic childhood-onset (CO) GHD, 18 years after...

  8. Adult onset glycogen storage disease type II (adult onset Pompe disease): report and magnetic resonance images of two cases

    International Nuclear Information System (INIS)

    Del Gaizo, Andrew; Banerjee, Sima; Terk, Michael

    2009-01-01

    Glycogen storage disease type II (GSDII), also referred to as Pompe disease or acid maltase deficiency, is a rare inherited condition caused by a deficiency in acid alpha-glucosidase (GAA) enzyme activity. The condition is often classified by age of presentation, with infantile and late onset variants (Laforet et al. J Neurology 55:1122-8, 2000). Late onset tends to present with progressive proximal muscle weakness and respiratory insufficiency (Winkel et al. J Neurology 252:875-84, 2005). We report two cases of biopsy confirmed adult onset GSDII, along with key Magnetic Resonance (MR) images. (orig.)

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

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    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.

  10. Adult-Onset Metachromatic Leukodystrophy: Two Cases

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    Gaye Eryaşar

    2011-12-01

    Full Text Available Metachromatic Leukodystrophy(MLD is a lisosomal storage disorder which is characterized with arylsulphatase A deficiency. Enzyme deficiency results with demiyelination and storage of sulphatides in central nervous system.According to onset age;the disease has three major clinical forms as late infantile,juvenile and adult form. It is a rare disorder. For the patients who did not develop neurological findings bone marrow or hematopoietic stem cell transplantation may be effective as treatment.

  11. Circulating neural antibodies in unselected children with new-onset seizures.

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    Garcia-Tarodo, Stephanie; Datta, Alexandre N; Ramelli, Gian P; Maréchal-Rouiller, Fabienne; Bien, Christian G; Korff, Christian M

    2018-05-01

    The role of autoimmunity and neural antibodies is increasingly recognized in different forms of seizures and epilepsy. Their prevalence in new-onset epilepsy has also recently been the focus of several clinical cohorts in the adult and pediatric population, with positive titers in 10-11% of cases. Our aim was to determine the seropositivity at the first seizure onset in a non-selective group of children. We conducted a prospective multicenter cohort study recruiting children aged 0-16 years with new-onset seizures presenting at the In- and Outpatient Pediatric Neurology Departments of three Children's Hospitals in Switzerland between September 2013 and April 2016. Neural antibodies were screened within the first 6 months of a first seizure and when positive, repeated at 1 month and 6 months follow-up. A total of 103 children were enrolled with a mean age at presentation of 5 years (range 1 day-15 years 9 months). The majority (n = 75) presented with generalized seizures and 6 had status epilepticus lasting > 30 min. At the time of onset, 55% of patients had fever, 24% required emergency seizure treatment and 27% hospitalization. Epilepsy was diagnosed at follow-up in 18%. No specific antibody was found. Serum antibodies against the VGKC complex, without binding to the specific antigens LGI1 and CASPR2, were found in two patients. Four patients harbored not otherwise characterized antibodies against mouse neuropil. Specific neural antibodies are rarely found in an unselected population of children that present with a first seizure. Applying an extensive neuronal antibody profile in a child with new-onset seizures does not appear to be justified. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  12. Adult onset sporadic ataxias: a diagnostic challenge

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    Orlando Graziani Povoas Barsottini

    2014-03-01

    Full Text Available Patients with adult onset non-familial progressive ataxia are classified in sporadic ataxia group. There are several disease categories that may manifest with sporadic ataxia: toxic causes, immune-mediated ataxias, vitamin deficiency, infectious diseases, degenerative disorders and even genetic conditions. Considering heterogeneity in the clinical spectrum of sporadic ataxias, the correct diagnosis remains a clinical challenge. In this review, the different disease categories that lead to sporadic ataxia with adult onset are discussed with special emphasis on their clinical and neuroimaging features, and diagnostic criteria.

  13. Noninvasive evaluation of adult onset myopathy from carnitine palmitoyl transferase II deficiency using proton magnetic resonance spectroscopy.

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    Videen, J S; Haseler, L J; Karpinski, N C; Terkeltaub, R A

    1999-08-01

    The adult onset metabolic myopathy of carnitine palmitoyl transferase II (CPT II) deficiency is under-recognized, in part due to variable degrees of enzyme deficiency and symptomatology, as well as limitations in means for noninvasive evaluation. We describe a proton magnetic resonance spectroscopy (MRS) technique, using a standard clinical magnetic resonance imaging scanner, to diagnose and help monitor the response to therapy in adult CPT II deficiency. A 53-year-old woman presented with a long standing history of diffuse aching and fatigue provoked by high fat intake, fasting, or prolonged exertion. Muscle biopsy revealed myopathic features and a deficiency (33% of control) of CPT II activity with elevated palmitoyl carnitine. Proton MRS of the soleus muscle was performed using a 1.5 Tesla scanner before and during dietary therapy. Proton MRS revealed shortening of the transverse relaxation time (T2), consistent with increased acetylation of the carnitine pool. The symptoms resolved completely by treatment with frequent feedings of a high carbohydrate diet low in long chain fatty acids supplemented with medium chain triglycerides and L-carnitine. Recovery of normal muscle MRS and carnitine T2 relaxation was documented by the third month of therapy. Proton MRS is a novel, potentially useful, and readily available adjunct in the diagnosis and therapeutic monitoring of muscle CPT II deficiency.

  14. Growth hormone (GH) treatment increases serum insulin-like growth factor binding protein-3, bone isoenzyme alkaline phosphatase and forearm bone mineral content in young adults with GH deficiency of childhood onset

    DEFF Research Database (Denmark)

    Juul, A; Pedersen, S A; Sørensen, S

    1994-01-01

    Recent studies have demonstrated that growth hormone (GH)-deficient adults have a markedly decreased bone mineral content compared to healthy adults. However, there are conflicting results regarding the effects of GH treatment on bone mineral content in GH-deficient adults. Therefore, we evaluated...... the effect of GH treatment on a marker of bone formation (bone alkaline phosphatase), hepatic excretory function and distal forearm bone mineral content in GH-deficient adults. Growth hormone was administered subcutaneously in 21 adults (13 males and 8 females) with GH deficiency of childhood onset for 4...

  15. Treatment and outcome of adult-onset neuroblastoma.

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    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.

  16. Iron Deficiency Anemia in Adult Onset Still's Disease with a Serum Ferritin of 26,387 μg/L

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    Sheetal Patel

    2011-01-01

    Full Text Available Serum ferritin rises in the anemia of chronic inflammation reflecting increased iron storage and other changes mediated by inflammation. When iron deficiency coexists, the ferritin may not always decline into the subnormal range. We describe the rare interaction of iron deficiency with the extreme hyperferritinemia characteristic of adult onset Still's disease. The combination has clinical relevance and allows deductions about the presence of serum ferritin at 26,387 μg/L despite obvious iron depletion. The diagnosis of iron deficiency anemia was delayed and became fully obvious when her Still's disease remitted and serum ferritin decreased to 6.5 μg/L. The coexistence of iron deficiency should be considered when evaluating a patient with anemia of chronic inflammation even when the ferritin level is elevated several hundredfold. Further insights on ferritin metabolism in Still's disease are suggested by the likelihood that the patient's massive hyperferritinemia in the acute phase of Still's disease was almost entirely of the iron-free apoferritin form.

  17. Late onset arginase deficiency presenting with encephalopathy and midbrain hyperintensity

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    Boby Varkey Maramattom

    2016-01-01

    Full Text Available Urea cycle disorders (UCD are very rare metabolic disorders that present with encephalopathy and hyperammonemia. Of the UCDs, Arginase deficiency (ARD is the rarest and presents in childhood with a progressive spastic diplegia or seizures. Acute presentation in adulthood is extremely unusual. [1] We present the first case of adult onset ARD presenting with encephalopathy and diffusion weighted MRI findings that resembled a moustache in the midbrain.

  18. Focus on growth hormone deficiency and bone in adults.

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    Tritos, Nicholas A

    2017-02-01

    Growth hormone (GH) exerts several effects on the skeleton, mediated either directly or indirectly, leading to increased bone formation and resorption rates. Patients with growth hormone deficiency (GHD) of adult onset have decreased bone mineral density (BMD) and increased fracture risk. Some, but not all, studies have found that adults with childhood onset GHD also have lower BMD than healthy controls. Adults with GHD of childhood onset have smaller bone dimensions, leading to possible underestimation of areal BMD (measured by dual energy X-ray absorptiometry), thus potentially confounding the interpretation of densitometric data. Available data suggest that patients with childhood onset GHD are at increased fracture risk. Prospective studies and some clinical trials found that GH replacement for at least 18-24 months leads to increased BMD. Retrospective and prospective data suggest that GH replacement is associated with decreased fracture risk in adults. However, data from randomized clinical trials are lacking. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. The clinical syndrome of specific antibody deficiency in children.

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    Boyle, R J; Le, C; Balloch, A; Tang, M L-K

    2006-12-01

    Specific antibody deficiency (SAD) is an immune deficiency which has been reported in adults and children with recurrent respiratory tract infections; however, the clinical features of SAD are not well described. This study evaluated formally the clinical syndrome of SAD, by comparing the clinical features of children with SAD and those of children with recurrent infection but normal immune function tests. SAD was defined as an adequate IgG antibody response to less than 50% of 12 pneumococcal serotypes tested following 23-valent unconjugated pneumococcal immunization. An adequate IgG antibody response was defined as a post-immunization titre of >or= 1.3 microg/ml or >or= four times the preimmunization value. Seventy-four children with recurrent infection were evaluated where immune deficiencies other than SAD had been excluded. Eleven (14.9%) of these children had SAD. Clinical features differed between the group with SAD and the group with normal antibody responses. A history of otitis media, particularly in association with chronic otorrhoea was associated with SAD [relative risk (RR) of SAD in those with chronic otorrhoea 4.64 (P = 0.02)]. SAD was associated with allergic disease, particularly allergic rhinitis [RR of SAD in those with allergic rhinitis 3.77 (P = 0.04)]. These two clinical associations of SAD were independent in this study [RR of chronic otorrhoea in those with allergic rhinitis 0.85 (P = 0.28)]. SAD was not an age-related phenomenon in this population. SAD has a distinct clinical phenotype, presenting as recurrent infection associated with chronic otorrhoea and/or allergic disease, and the condition should be sought in children with these features.

  20. Growth hormone (GH) treatment increases serum insulin-like growth factor binding protein-3, bone isoenzyme alkaline phosphatase and forearm bone mineral content in young adults with GH deficiency of childhood onset

    DEFF Research Database (Denmark)

    Juul, A; Pedersen, S A; Sørensen, S

    1994-01-01

    Recent studies have demonstrated that growth hormone (GH)-deficient adults have a markedly decreased bone mineral content compared to healthy adults. However, there are conflicting results regarding the effects of GH treatment on bone mineral content in GH-deficient adults. Therefore, we evaluated...... the effect of GH treatment on a marker of bone formation (bone alkaline phosphatase), hepatic excretory function and distal forearm bone mineral content in GH-deficient adults. Growth hormone was administered subcutaneously in 21 adults (13 males and 8 females) with GH deficiency of childhood onset for 4...... months in a double-blind, placebo-controlled GH trial, while 13 of the patients then received further GH for an additional 14 months. Serum insulin-like growth factor I (IGF-I) increased significantly from 100 to 279 micrograms/l and IGF binding protein-3 (IGFBP-3) from 1930 to 3355 micrograms/l after 4...

  1. Efficacy of growth hormone therapy in adults with childhood-onset growth hormone deficiency

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    Ja Hye Kim

    2014-03-01

    Full Text Available PurposeGrowth hormone (GH plays a key role in the regulation of body composition, lipid metabolism, and quality of life in adults with GH deficiency (GHD. This study investigated changes in laboratory findings and body composition after GH recommencement for adult GHD and analyzed correlation between GH interruption period and endocrine or anthropometric parameters.MethodsA total of 45 patients (17 females and 28 males diagnosed with childhood-onset GHD (CO-GHD were investigated and all patients had organic brain lesions. Patients diagnosed CO-GHD were retested to confirm adult GHD at age 20.4±5.0 years (18.0-32.1 years. Recombinant human GH was administered at a dose of 0.44 mg/day. Clinical and laboratory parameters such as weight, height, body mass index (BMI, serum insulin-like growth factor 1 (IGF-1, serum total cholesterol, high-density lipoprotein (HDL cholesterol, low-density lipoprotein (LDL cholesterol, and triglyceride levels, were compared between baseline and 12 months after treatment using paired t-test. In addition, correlation between GH interruption period and clinical parameters including BMI, lipid profile, IGF-1, and IGFBP-3, was analyzed.ResultsOf 45 patients, 33 patients had GH interruption period of 4.3±3.6 years (0.7-12.5 years. Serum HDL-cholesterol level increased significantly, whereas LDL-cholesterol decreased after 1 year of GH replacement therapy. However, body weight and BMI showed no significant changes after 1 year of GH replacement therapy. There were no significant correlations between GH interruption period and lipid profile or anthropometric parameters.ConclusionBMI and body weight were not affected by GH replacement. However, GH replacement in adults with GHD offers benefits in lipid metabolism.

  2. Osteomalacia in a Case of Adult-Onset Bartter Syndrome

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    Rashid Naseem Khan

    2018-01-01

    Full Text Available Bartter syndrome is a rare heterogeneous disease characterised by a deficiency in sodium and chloride absorption. Gain-of-function mutations in the CASR gene have been described in some patients with Bartter syndrome associated with hypocalcaemia and hypercalciuria. We describe a case of adult-onset Bartter syndrome with hypocalcaemia severe enough to cause osteomalacia.

  3. Study of gastrointestinal polypeptides controlling gastric acid secretion in patients with primary antibody deficiency.

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    Alonso Falcón, F; Codoceo Alquinta, R; Polanco Allué, I; Aguado Gil, A; Fontán Casariego, G

    1999-01-01

    Gastric abnormalities are a common feature in patients with primary antibody deficiency. The most important problem is the high incidence of stomach cancer found in these patients. Chronic atrophic gastritis with pernicious anemia is also a common finding that predisposes to gastric adenocarcinoma. The aim of the present study was to identify factors predictive of high risk for developing gastric cancer in patients with primary antibody deficiency. We studied gastric hormones (gastrin, somatostatin and gastrin-releasing peptide, GRP) in 47 patients (23 children and 24 adults) with primary antibody deficiency. In accordance with the World Health Organization (WHO) classification, patients were diagnosed as having X-linked agammaglobulinemia (Bruton disease) in 13 cases, common variable immunodeficiency in 28, and hypogammaglobulinemia with hyperIgM in 6. Gastric biopsy was performed in 22 patients (16 children and 6 adults). Hormone determinations were carried out by radioimmunoassay. Baseline serum gastrin levels were normal or increased compared with controls, but the response to stimulation with a hyperproteic diet was delayed in 18 patients and lower than in controls in 7. In 4 adult patients, all with pernicious anemia, gastric biopsy revealed chronic atrophic gastritis involving the stomach corpus and antrum (type B gastritis). The absence of a normal response of gastrin secretion to stimulation with a hyperproteic diet may be explained by this finding. Serum somatostatin and GRP levels were higher than in controls. No correlations were found between these findings and patient age, type of immunodeficiency or duration of clinical manifestations.

  4. Primary vs. secondary antibody deficiency: clinical features and infection outcomes of immunoglobulin replacement.

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    Sai S Duraisingham

    Full Text Available Secondary antibody deficiency can occur as a result of haematological malignancies or certain medications, but not much is known about the clinical and immunological features of this group of patients as a whole. Here we describe a cohort of 167 patients with primary or secondary antibody deficiencies on immunoglobulin (Ig-replacement treatment. The demographics, causes of immunodeficiency, diagnostic delay, clinical and laboratory features, and infection frequency were analysed retrospectively. Chemotherapy for B cell lymphoma and the use of Rituximab, corticosteroids or immunosuppressive medications were the most common causes of secondary antibody deficiency in this cohort. There was no difference in diagnostic delay or bronchiectasis between primary and secondary antibody deficiency patients, and both groups experienced disorders associated with immune dysregulation. Secondary antibody deficiency patients had similar baseline levels of serum IgG, but higher IgM and IgA, and a higher frequency of switched memory B cells than primary antibody deficiency patients. Serious and non-serious infections before and after Ig-replacement were also compared in both groups. Although secondary antibody deficiency patients had more serious infections before initiation of Ig-replacement, treatment resulted in a significant reduction of serious and non-serious infections in both primary and secondary antibody deficiency patients. Patients with secondary antibody deficiency experience similar delays in diagnosis as primary antibody deficiency patients and can also benefit from immunoglobulin-replacement treatment.

  5. Primary vs. Secondary Antibody Deficiency: Clinical Features and Infection Outcomes of Immunoglobulin Replacement

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    Duraisingham, Sai S.; Buckland, Matthew; Dempster, John; Lorenzo, Lorena; Grigoriadou, Sofia; Longhurst, Hilary J.

    2014-01-01

    Secondary antibody deficiency can occur as a result of haematological malignancies or certain medications, but not much is known about the clinical and immunological features of this group of patients as a whole. Here we describe a cohort of 167 patients with primary or secondary antibody deficiencies on immunoglobulin (Ig)-replacement treatment. The demographics, causes of immunodeficiency, diagnostic delay, clinical and laboratory features, and infection frequency were analysed retrospectively. Chemotherapy for B cell lymphoma and the use of Rituximab, corticosteroids or immunosuppressive medications were the most common causes of secondary antibody deficiency in this cohort. There was no difference in diagnostic delay or bronchiectasis between primary and secondary antibody deficiency patients, and both groups experienced disorders associated with immune dysregulation. Secondary antibody deficiency patients had similar baseline levels of serum IgG, but higher IgM and IgA, and a higher frequency of switched memory B cells than primary antibody deficiency patients. Serious and non-serious infections before and after Ig-replacement were also compared in both groups. Although secondary antibody deficiency patients had more serious infections before initiation of Ig-replacement, treatment resulted in a significant reduction of serious and non-serious infections in both primary and secondary antibody deficiency patients. Patients with secondary antibody deficiency experience similar delays in diagnosis as primary antibody deficiency patients and can also benefit from immunoglobulin-replacement treatment. PMID:24971644

  6. Adult-onset tic disorders

    NARCIS (Netherlands)

    Eapen, [No Value; Lees, AJ; Lakke, JPWF; Trimble, MR; Robertson, MM

    We report on 8 patients with adult-onset motor tics and vocalisations. Three had compulsive tendencies in childhood and 3 had a family history of tics or obsessive-compulsive behaviour. In comparison with DSM-classified, younger-onset Gilles de la Tourette syndrome, adult-onset tic disorders are

  7. Hypocretin deficiency develops during onset of human narcolepsy with cataplexy

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    Savvidou, Andri; Knudsen, Stine; Olsson-Engman, Mia

    2013-01-01

    Although hypothesized through animal studies, a temporal and causal association between hypocretin deficiency and the onset of narcolepsy with cataplexy (NC) has never been proven in humans.......Although hypothesized through animal studies, a temporal and causal association between hypocretin deficiency and the onset of narcolepsy with cataplexy (NC) has never been proven in humans....

  8. Adult-Onset Type 1 Diabetes and Pregnancy: Three Case Reports

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    Barbara Bonsembiante

    2013-01-01

    Full Text Available From 5% to 10% of diabetic patients have type 1 diabetes. Here we describe three cases of adult-onset type 1 diabetes in pregnancy treated at our clinic between 2009 and 2012. Two patients came for specialist examination during pregnancy, the third after pregnancy. These women had no prior overt diabetes and shared certain characteristics, that is, no family diabetes history, age over 35, normal prepregnancy BMI, need for insulin therapy as of the early weeks of pregnancy, and high-titer anti-GAD antibody positivity. The patients had persistent diabetes after delivery, suggesting that they developed adult-onset type 1 diabetes during pregnancy. About 10% of GDM patients become pancreatic autoantibody positive and the risk of developing overt diabetes is higher when two or more autoantibodies are present (particularly GAD and ICA. GAD-Ab shows the highest sensitivity for type 1 diabetes prediction. We need to bear in mind that older patients might conceivably develop an adult-onset type 1 diabetes during or after pregnancy. So we suggest that women with GDM showing the described clinical features shall be preferably tested for autoimmunity. Pregnant patients at risk of type 1 diabetes should be identified to avoid the maternal and fetal complications and the acute onset of diabetes afterwards.

  9. Morphea in Adults and Children Cohort VI: A cross-sectional comparison of outcomes between adults with pediatric-onset and adult-onset morphea

    Science.gov (United States)

    Condie, Daniel; Grabell, Daniel; Jacobe, Heidi

    2014-01-01

    Objective Few studies have looked at outcomes of adults with pediatric-onset morphea. The objective of the present study was to compare clinical outcomes and health-related quality of life in adults with pediatric-onset morphea to those of patients with adult-onset morphea. Methods Participants in the study were drawn from the Morphea in Adults and Children Cohort and included 68 adults with pediatric-onset morphea and 234 patients with adult-onset morphea. Outcome measures included the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT), physical exam findings, and quality of life questionnaires. Results Adults with pediatric-onset morphea were younger, had longer disease duration, and were more likely to have the linear subtype of morphea. Patients with pediatric-onset disease were less likely to have active disease. Among patients with active disease, those with pediatric-onset morphea had less disease activity as measured by the LoSCAT. Patients with pediatric-onset disease had higher disease damage as measured by the Physician Global Assessment of Damage, but similar disease damage as measured by the Localized Scleroderma Skin Damage Index. Patients with pediatric-onset disease had more favorable quality of life scores for all measures that reached statistical significance. Conclusion Adults with pediatric-onset morphea differ from patients with adult-onset disease with respect to subtype, disease activity, disease damage, and health-related quality of life. PMID:25156342

  10. Late-Onset N-Acetylglutamate Synthase Deficiency: Report of a Paradigmatic Adult Case Presenting with Headaches and Review of the Literature

    Science.gov (United States)

    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

  11. Late-Onset N-Acetylglutamate Synthase Deficiency: Report of a Paradigmatic Adult Case Presenting with Headaches and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Catia Cavicchi

    2018-01-01

    Full Text Available 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.

  12. ESX-5-deficient Mycobacterium marinum is hypervirulent in adult zebrafish

    KAUST Repository

    Weerdenburg, Eveline M.

    2012-02-15

    ESX-5 is a mycobacterial type VII protein secretion system responsible for transport of numerous PE and PPE proteins. It is involved in the induction of host cell death and modulation of the cytokine response in vitro. In this work, we studied the effects of ESX-5 in embryonic and adult zebrafish using Mycobacterium marinum. We found that ESX-5-deficient M.marinum was slightly attenuated in zebrafish embryos. Surprisingly, the same mutant showed highly increased virulence in adult zebrafish, characterized by increased bacterial loads and early onset of granuloma formation with rapid development of necrotic centres. This early onset of granuloma formation was accompanied by an increased expression of pro-inflammatory cytokines and tissue remodelling genes in zebrafish infected with the ESX-5 mutant. Experiments using RAG-1-deficient zebrafish showed that the increased virulence of the ESX-5 mutant was not dependent on the adaptive immune system. Mixed infection experiments with wild-type and ESX-5 mutant bacteria showed that the latter had a specific advantage in adult zebrafish and outcompeted wild-type bacteria. Together our experiments indicate that ESX-5-mediated protein secretion is used by M.marinum to establish a moderate and persistent infection. © 2012 Blackwell Publishing Ltd.

  13. Antibody deficiency in patients with frequent exacerbations of Chronic Obstructive Pulmonary Disease (COPD).

    Science.gov (United States)

    McCullagh, Brian N; Comellas, Alejandro P; Ballas, Zuhair K; Newell, John D; Zimmerman, M Bridget; Azar, Antoine E

    2017-01-01

    Chronic Obstructive Pulmonary Disease is the third leading cause of death in the US, and is associated with periodic exacerbations, which account for the largest proportion of health care utilization, and lead to significant morbidity, mortality, and worsening lung function. A subset of patients with COPD have frequent exacerbations, occurring 2 or more times per year. Despite many interventions to reduce COPD exacerbations, there is a significant lack of knowledge in regards to their mechanisms and predisposing factors. We describe here an important observation that defines antibody deficiency as a potential risk factor for frequent COPD exacerbations. We report a case series of patients who have frequent COPD exacerbations, and who were found to have an underlying primary antibody deficiency syndrome. We also report on the outcome of COPD exacerbations following treatment in a subset with of these patients with antibody deficiency. We identified patients with COPD who had 2 or more moderate to severe exacerbations per year; immune evaluation including serum immunoglobulin levels and pneumococcal IgG titers was performed. Patients diagnosed with an antibody deficiency syndrome were treated with either immunoglobulin replacement therapy or prophylactic antibiotics, and their COPD exacerbations were monitored over time. A total of 42 patients were identified who had 2 or more moderate to severe COPD exacerbations per year. Twenty-nine patients had an underlying antibody deficiency syndrome: common variable immunodeficiency (8), specific antibody deficiency (20), and selective IgA deficiency (1). Twenty-two patients had a follow-up for at least 1 year after treatment of their antibody deficiency, which resulted in a significant reduction of COPD exacerbations, courses of oral corticosteroid use and cumulative annual dose of oral corticosteroid use, rescue antibiotic use, and hospitalizations for COPD exacerbations. This case series identifies antibody deficiency as a

  14. Clinical significance of detection of antibodies to fetal and adult acetylcholine receptors in myasthenia gravis

    Institute of Scientific and Technical Information of China (English)

    Qi-Guang Shi; Zhi-Hong Wang; Xiao-Wei Ma; Da-Qi Zhang; Chun-Sheng Yang; Fu-Dong Shi; Li Yang

    2012-01-01

    Objective To evaluate the frequency,distribution and clinical significance of the antibodies to the fetal and/or adult acetylcholine receptor (AChR) in patients with myasthenia gravis (MG).Methods AChR antibodies were detected by cell-based assay in the serum of ocular MG (OMG) (n =90) and generalized MG (GMG) patients (n =110).The fetaltype (2α∶ β∶ γ∶ δ) and adult-type (2α∶ β∶ ε∶ δ) AChR were used as antigens,and their relevance to disease presentation was assessed.Results The overall frequencies of anti-adult and anti-fetal AChR antibodies were similar in all 200 patients examined,with 14 having serum specific to the AChR-γ subunit,and 22 to the AChR-ε subunit.The overall sensitivity when using the fetal and adult AChR antibodies was higher than that when using the fetal AChR antibody only (P =0.015).Compared with OMG patients,the mean age at disease onset and the positive ratio of antibodies to both isoforms of the AChR were significantly higher in patients who subsequently progressed to GMG.Older patients and patients with both anti-fetal and anti-adult AChR antibodies had a greater risk for developing generalized disease [odds ratio (OR),1.03;95% confidence interval (CI),1.01-1.06 and OR,5.09;95% CI,2.23-11.62].Conclusion Using both fetal-and adulttype AChRs as the antigens may be more sensitive than using either subtype.Patients with serum specific to both isoforms are at a greater risk of progressing to GMG.Patients with disease onset at an advanced age appear to have a higher frequency of GMG conversion.

  15. Severe sensory neuropathy in patients with adult-onset multiple acyl-CoA dehydrogenase deficiency.

    Science.gov (United States)

    Wang, Zhaoxia; Hong, Daojun; Zhang, Wei; Li, Wurong; Shi, Xin; Zhao, Danhua; Yang, Xu; Lv, He; Yuan, Yun

    2016-02-01

    Multiple Acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder of fatty acid oxidation. Most patients with late-onset MADD are clinically characterized by lipid storage myopathy with dramatic responsiveness to riboflavin treatment. Abnormalities of peripheral neuropathy have rarely been reported in patients with late-onset MADD. We describe six patients who presented with proximal limb weakness and loss of sensation in the distal limbs. Muscle biopsy revealed typical myopathological patterns of lipid storage myopathy and blood acylcarnitine profiles showed a combined elevation of multiple acylcarnitines supporting the diagnosis of MADD. However, nerve conduction investigations and sural nerve biopsies in these patients indicated severe axonal sensory neuropathy. Causative ETFDH gene mutations were found in all six cases. No other causative gene mutations were identified in mitochondrial DNA and genes associated with hereditary neuropathies through next-generation-sequencing panel. Late-onset patients with ETFDH mutations can present with proximal muscle weakness and distal sensory neuropathy, which might be a new phenotypic variation, but the precise underlying pathogenesis remains to be elucidated. Copyright © 2015. Published by Elsevier B.V.

  16. Limbic encephalitis associated with anti-voltage-gated potassium channel complex antibodies as a cause of adult-onset mesial temporal lobe epilepsy.

    Science.gov (United States)

    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 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.

  17. Adult onset tic disorders

    OpenAIRE

    Chouinard, S.; Ford, B.

    2000-01-01

    BACKGROUND—Tic disorders presenting during adulthood have infrequently been described in the medical literature. Most reports depict adult onset secondary tic disorders caused by trauma, encephalitis, and other acquired conditions. Only rare reports describe idiopathic adult onset tic disorders, and most of these cases represent recurrent childhood tic disorders.
OBJECTIVE—To describe a large series of patients with tic disorders presenting during adulthood, to compare cl...

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

    Science.gov (United States)

    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.

  19. Adult-onset offenders: Is a tailored theory warranted?

    Science.gov (United States)

    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

  20. Antithyroid Antibodies Are Implicated in Epileptogenesis of Adult Patients With Epilepsy.

    Science.gov (United States)

    Tsai, Meng-Han; Fu, Ting-Ying; Chen, Nai-Ching; Shih, Fu-Yuan; Lu, Yan-Ting; Cheng, Mei-Yun; Chuang, Hung-Yi; Chuang, Yao-Chung

    2015-07-01

    Antithyroid antibodies (Abs) are associated with epilepsy in steroid-responsive encephalopathy, but have been rarely studied in unselected epilepsy patients. This study aimed to characterize the prevalence and associated factors of antithyroid Abs and other auto-Abs in adult patients with epilepsy.Epilepsy patients without autoimmune disorders were surveyed for antinuclear antibody (ANA), anti-β2 glycoprotein 1 antibody (aβ2GP1), anticardiolipin IgG Ab, antimicrosomal antibody (AMA), antithyroglobulin antibody (ATA), and thyroid function test.Of 319 patients, 75 (23.5%) were positive for at least 1 Ab. The most common Ab was anticardiolipin antibody (aCL) (30/319, 9.4%), followed by AMA (24/319, 7.5%), ANA (18/319, 5.6%), aβ2GP1 (18/319, 6.5%), and ATA (6/319, 3.25%). Antimicrosomal Abs were significantly more frequent in patients who were female, older at disease onset, older at the time of study, and had unknown seizure etiology. The presence of aCL was significantly associated with more frequent seizures. Most patients with antithyroid Ab were female and had focal seizures with unknown etiology.The association of different auto-Abs with different factors suggests that they may have different roles in adult patients with epilepsy. Recurrent seizures and certain antiepileptic medications may cause the production of aCL. The role of antithyroid Abs in adult focal epilepsy with unknown cause, especially in females, warrants further evaluation because of the potential implications on treatment.

  1. Metabolic impact of adult-onset, isolated, growth hormone deficiency (AOiGHD due to destruction of pituitary somatotropes.

    Directory of Open Access Journals (Sweden)

    Raul M Luque

    2011-01-01

    Full Text Available Growth hormone (GH inhibits fat accumulation and promotes protein accretion, therefore the fall in GH observed with weight gain and normal aging may contribute to metabolic dysfunction. To directly test this hypothesis a novel mouse model of adult onset-isolated GH deficiency (AOiGHD was generated by cross breeding rat GH promoter-driven Cre recombinase mice (Cre with inducible diphtheria toxin receptor mice (iDTR and treating adult Cre(+/-,iDTR(+/- offspring with DT to selectively destroy the somatotrope population of the anterior pituitary gland, leading to a reduction in circulating GH and IGF-I levels. DT-treated Cre(-/-,iDTR(+/- mice were used as GH-intact controls. AOiGHD improved whole body insulin sensitivity in both low-fat and high-fat fed mice. Consistent with improved insulin sensitivity, indirect calorimetry revealed AOiGHD mice preferentially utilized carbohydrates for energy metabolism, as compared to GH-intact controls. In high-fat, but not low-fat fed AOiGHD mice, fat mass increased, hepatic lipids decreased and glucose clearance and insulin output were impaired. These results suggest the age-related decline in GH helps to preserve systemic insulin sensitivity, and in the context of moderate caloric intake, prevents the deterioration in metabolic function. However, in the context of excess caloric intake, low GH leads to impaired insulin output, and thereby could contribute to the development of diabetes.

  2. Haematinic deficiency and macrocytosis in middle-aged and older adults.

    Directory of Open Access Journals (Sweden)

    Therese McNamee

    Full Text Available OBJECTIVE: To assess the prevalence and determinants of haematinic deficiency (lack of B12 folate or iron and macrocytosis in blood from a national population-based study of middle-aged and older adults. METHODS: A cross-sectional study involving 1,207 adults aged ≥45 years, recruited from a sub-study of the Irish National Survey of Lifestyle Attitudes and Nutrition (SLÁN 2007. Participants completed a health and lifestyle questionnaire and a standard food frequency questionnaire. Non-fasting blood samples were obtained for measurement of full blood count and expert morphological assessment, serum ferritin, soluble transferrin receptor assay (sTfR, B12, folate and coeliac antibodies. Blood samples were also assayed for thyroid function (T4, TSH, liver function, aminotransferase (AST and gamma-glutamyl transferase (GGT. RESULTS: The overall prevalence (95% C.I. of anaemia (Hb 21 nmol/ml only 2.3% were iron-deficient. 3.0% and 2.7% were found to have low levels of serum folate (99fl was detected in 8.4% of subjects. Strong, significant and independent associations with macrocytosis were observed for lower social status, current smoking status, moderate to heavy alcohol intake, elevated GGT levels, deficiency of folate and vitamin B12, hypothyroidism and coeliac disease. The population attributable fraction (PAF for macrocytosis associated with elevated GGT (25.0% and smoking (24.6% was higher than for excess alcohol intake (6.3%, folate deficiency (10.5% or vitamin B12 (3.4%. CONCLUSIONS: Haematinic deficiency and macrocytosis are common in middle-aged/older adults in Ireland. Macrocytosis is more likely to be attributable to an elevated GGT and smoking than vitamin B12 or folate deficiency.

  3. Comparison of outcomes in adults with pediatric-onset morphea and those with adult-onset morphea: a cross-sectional study from the morphea in adults and children cohort.

    Science.gov (United States)

    Condie, Daniel; Grabell, Daniel; Jacobe, Heidi

    2014-12-01

    Few studies have examined outcomes in adults with pediatric-onset morphea. The objective of the present study was to compare clinical outcomes and health-related quality of life (HRQOL) in adults with onset of morphea in childhood to those in patients with adult onset of morphea. Participants in the study were drawn from the Morphea in Adults and Children cohort and included 68 adults with pediatric-onset morphea and 234 patients with adult-onset morphea. Outcome measures included the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT), physical examination findings, and HRQOL questionnaires. Adults with pediatric-onset morphea were younger, had longer disease duration, and were more likely to have the linear subtype of morphea. Patients with pediatric-onset disease were less likely to have active disease. Among patients with active disease, those with pediatric-onset morphea had less disease activity as measured by the LoSCAT. Patients with pediatric-onset disease had higher severity of disease damage when measured by the physician's global assessment of damage, but had similar levels of disease damage when measured by the Localized Scleroderma Skin Damage Index. Patients with pediatric-onset disease had more favorable HRQOL scores for all measures, all of which were statistically significantly different from those in patients with adult-onset morphea. Adults with pediatric-onset morphea differ from patients with adult-onset disease with respect to disease subtype, severity of disease activity and damage, and levels of HRQOL. Copyright © 2014 by the American College of Rheumatology.

  4. Glutamic acid decarboxylase antibodies are indicators of the course, but not of the onset, of diabetes in middle-aged adults: the Atherosclerosis Risk in Communities Study

    Directory of Open Access Journals (Sweden)

    A. Vigo

    2007-07-01

    Full Text Available To efficiently examine the association of glutamic acid decarboxylase antibody (GADA positivity with the onset and progression of diabetes in middle-aged adults, we performed a case-cohort study representing the ~9-year experience of 10,275 Atherosclerosis Risk in Communities Study participants, initially aged 45-64 years. Antibodies to glutamic acid decarboxylase (GAD65 were measured by radioimmunoassay in 580 incident diabetes cases and 544 non-cases. The overall weighted prevalence of GADA positivity (³1 U/mL was 7.3%. Baseline risk factors, with the exception of smoking and interleukin-6 (P £ 0.02, were generally similar between GADA-positive and -negative individuals. GADA positivity did not predict incident diabetes in multiply adjusted (HR = 1.04; 95%CI = 0.55, 1.96 proportional hazard analyses. However, a small non-significant adjusted risk (HR = 1.29; 95%CI = 0.58, 2.88 was seen for those in the highest tertile (³2.38 U/mL of positivity. GADA-positive and GADA-negative non-diabetic individuals had similar risk profiles for diabetes, with central obesity and elevated inflammation markers, aside from glucose, being the main predictors. Among diabetes cases at study's end, progression to insulin treatment increased monotonically as a function of baseline GADA level. Overall, being GADA positive increased risk of progression to insulin use almost 10 times (HR = 9.9; 95%CI = 3.4, 28.5. In conclusion, in initially non-diabetic middle-aged adults, GADA positivity did not increase diabetes risk, and the overall baseline profile of risk factors was similar for positive and negative individuals. Among middle-aged adults, with the possible exception of those with the highest GADA levels, autoimmune pathophysiology reflected by GADA may become clinically relevant only after diabetes onset.

  5. Antibodies in juvenile-onset myositis.

    Science.gov (United States)

    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.

  6. Anemia and hematinic deficiencies in gastric parietal cell antibody-positive and antibody-negative erosive oral lichen planus patients with thyroid antibody positivity.

    Science.gov (United States)

    Chang, Julia Y-F; Chen, I-Chang; Wang, Yi-Ping; Wu, Yu-Hsueh; Chen, Hsin-Ming; Sun, Andy

    2016-11-01

    Serum gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) are found in some erosive oral lichen planus (EOLP) patients. This study assessed whether serum GPCA, TGA and TMA and EOLP itself played significant roles in causing anemia and hematinic deficiencies in TGA/TMA-positive EOLP patients with GPCA positivity (GPCA + /TGA/TMA/EOLP patients) or negativity (GPCA - /TGA/TMA/EOLP patients). The mean corpuscular volume (MCV) and mean blood hemoglobin (Hb), iron, vitamin B12, and folic acid levels were measured and compared between any two of the four groups of 29 GPCA + /TGA/TMA/EOLP patients, 80 GPCA - /TGA/TMA/EOLP patients, 198 all antibodies-negative EOLP patients (Abs - /EOLP patients), and 218 healthy control individuals. GPCA + /TGA/TMA/EOLP patients had significantly lower mean Hb and vitamin B12 levels as well as significantly greater frequencies of Hb, iron, and vitamin B12 deficiencies than healthy controls. GPCA + /TGA/TMA/EOLP patients had significantly lower serum vitamin B12 level and higher MCV as well as a significantly greater frequency of vitamin B12 deficiency than GPCA - /TGA/TMA/EOLP patients. Furthermore, both GPCA - /TGA/TMA/EOLP and Abs - /EOLP patients did have significantly lower mean Hb, MCV, and iron (for women only) levels, as well as significantly greater frequencies of Hb and iron deficiencies than healthy controls. However, there were no significant differences in measured blood data between GPCA - /TGA/TMA/EOLP and Abs - /EOLP patients. We conclude that serum GPCA is the major factor causing vitamin B12 deficiency, macrocytosis and pernicious anemia in GPCA + /TGA/TMA/EOLP patients. ELOP itself but not TGA/TMA positivity plays a significant role in causing anemia and hematinic deficiencies in GPCA - /TGA/TMA/EOLP patients. Copyright © 2016. Published by Elsevier B.V.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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 adult-onset disease), and comorbidities (hypertension was more frequent in adult-onset group, p 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.

  9. Antibodies against deamidated gliadin peptides identify adult coeliac disease patients negative for antibodies against endomysium and tissue transglutaminase.

    Science.gov (United States)

    Dahle, C; Hagman, A; Ignatova, S; Ström, M

    2010-07-01

    This study was done to evaluate the diagnostic utility of antibodies against deamidated gliadin peptides compared to traditional markers for coeliac disease. To evaluate diagnostic utility of antibodies against deamidated gliadin peptide (DGP). Sera from 176 adults, referred for endoscopy without previous analysis of antibodies against tissue transglutaminase (tTG) or endomysium (EmA), were retrospectively analysed by ELISAs detecting IgA/IgG antibodies against DGP or a mixture of DGP and tTG, and compared with IgA-tTG and EmA. Seventy-nine individuals were diagnosed with coeliac disease. Receiver operating characteristic analyses verified the manufacturers' cut-off limits except for IgA/IgG-DGP/tTG. In sera without IgA deficiency, the sensitivity was higher for IgA/IgG-DGP (0.85-0.87) compared with IgA-tTg (0.76) and EmA (0.61). All tests showed high specificity (0.95-1.00). Eighteen coeliac disease-sera were negative regarding IgA-tTG, nine of which were positive for IgA/IgG-DGP. Sera from coeliac disease-patients >70 years were more often negative for IgA-tTG (50%) and IgA/IgG-DGP (36%) than younger patients (15% and 8% respectively) (P adult coeliac disease patients negative for antibodies against endomysium and tissue transglutaminase. Serology is often negative in elderly patients with coeliac disease; a small bowel biopsy should therefore be performed generously before coeliac disease is excluded.

  10. A treatable cause of myelopathy and vision loss mimicking neuromyelitis optica spectrum disorder: late-onset biotinidase deficiency.

    Science.gov (United States)

    Yilmaz, Sanem; Serin, Mine; Canda, Ebru; Eraslan, Cenk; Tekin, Hande; Ucar, Sema Kalkan; Gokben, Sarenur; Tekgul, Hasan; Serdaroglu, Gul

    2017-06-01

    Biotinidase deficiency is characterized by severe neurological manifestations as hypotonia, lethargy, ataxia, hearing loss, seizures and developmental retardation in its classical form. Late-onset biotinidase deficiency presents distinctly from the classical form such as limb weakness and vision problems. A 14-year-old boy presented with progressive vision loss and upper limb weakness. The patient was initiated steroid therapy with a preliminary diagnosis of neuromyelitis optica spectrum disorder due to the craniospinal imaging findings demonstrating optic nerve, brainstem and longitudinally extensive spinal cord involvement. Although the patient exhibited partial clinical improvement after pulse steroid therapy, craniocervical imaging performed one month after the initiation of steroid therapy did not show any regression. The CSF IgG index was <0.8 (normal: <0.8), oligoclonal band and aquaporin-4 antibodies were negative. Metabolic investigations revealed a low biotinidase enzyme activity 8% (0.58 nmoL/min/mL; normal range: 4.4 to 12). Genetic testing showed c.98-104delinsTCC and p.V457 M mutations in biotinidase (BTD) gene. At the third month of biotin replacement therapy, control craniospinal MRI demonstrated a complete regression of the lesions. The muscle strength of the case returned to normal. His visual acuity was 7/10 in the left eye and 9/10 in the right. The late-onset form of the biotinidase deficiency should be kept in mind in all patients with myelopathy with or without vision loss, particularly in those with inadequate response to steroid therapy. The family screening is important to identify asymptomatic individuals and timely treatment.

  11. Hyperammonemic coma in a patient with late-onset OTC deficiency

    Directory of Open Access Journals (Sweden)

    V. D’Onofrio

    2014-06-01

    Full Text Available Urea Cycle Disorders ( UCD are among the most common genetic diseases of the metabolism and ornithine transcarbamylase deficiency (OTC, an X-linked defect is the most frequent among them. It is responsible for hyperammonemia that can lead to chronic neurological illness and potentially to death in case of delayed diagnosis and treatment. With regards to the OTC deficiency there is great clinical heterogeneity with early-onset phenotypes with mostly poor prognosis and late-onset phenotypes with a better one. In the article it is reported the case of a 8 years old patient with diagnosis of OTC deficit with late-onset phenotype. The kid was brought to our hospital because of continuous vomiting and gastro- intestinal disorders, associated with irritability and lethargy later resulted into coma. Measurement of plasma ammonia concentration, followed by measurement of plasma amino acid and urine orotic acid levels allowed to diagnose the OTC deficit, lately confirmed by molecular genetic studies. The patient has been promptly treated with Sodium Phenylbutyrate, Arginine and discontinuing the protein intake. Gradually the ammonemia value decreased, and general and neurological conditions improved with resolution of the coma. To conclude, for patients presenting unexplained neurological symptoms, confusion and decreased level of consciousness, up to coma, urea cycle disorders and in particularly OTC deficiency should be considered in the differential diagnosis and an urgent ammonia level determined. In case of hyperammonemia, the treatment should be started immediately , even without a precise ethiologic diagnosis.

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

    Science.gov (United States)

    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…

  13. MRI in a case of adult-onset citrullinemia

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Y.F.; Huang, Y.C.; Liu, H.M. [Dept. of Radiology, National Taiwan University Hospital, Taipei (Taiwan); Hwu, W.L. [Dept. of Medical Genetics, National Taiwan University Hospital, Taipei (Taiwan)

    2001-10-01

    A 42-year-old man presented with a history of repeated episodes of consciousness disturbance for 5 years. The MRI showed abnormally high signal intensities on T2-weighted images at bilateral cingulate gyri, temporal lobes and insular regions, mimicking the finding of herpes simplex encephalitis. Hyperammonemia was disclosed. Serial work-up led to the diagnosis of adult-onset citrullinemia, deficiency of argininosuccinate synthetase. The clinical symptoms improved after diet control and medication. Follow-up MRI showed resolution of the abnormal signal intensities. The MRI findings of citrullinemia and other urea-cycle defects might be attributed to hyperammonemic encephalopathy, but the manifestations were varied. Similar distribution of the abnormalities in the MRI could be found in some reported cases and indicates probably vulnerable sites of hyperammonemic brain injury. (orig.)

  14. MRI in a case of adult-onset citrullinemia

    International Nuclear Information System (INIS)

    Chen, Y.F.; Huang, Y.C.; Liu, H.M.; Hwu, W.L.

    2001-01-01

    A 42-year-old man presented with a history of repeated episodes of consciousness disturbance for 5 years. The MRI showed abnormally high signal intensities on T2-weighted images at bilateral cingulate gyri, temporal lobes and insular regions, mimicking the finding of herpes simplex encephalitis. Hyperammonemia was disclosed. Serial work-up led to the diagnosis of adult-onset citrullinemia, deficiency of argininosuccinate synthetase. The clinical symptoms improved after diet control and medication. Follow-up MRI showed resolution of the abnormal signal intensities. The MRI findings of citrullinemia and other urea-cycle defects might be attributed to hyperammonemic encephalopathy, but the manifestations were varied. Similar distribution of the abnormalities in the MRI could be found in some reported cases and indicates probably vulnerable sites of hyperammonemic brain injury. (orig.)

  15. Late-onset form of beta-electron transfer flavoprotein deficiency

    DEFF Research Database (Denmark)

    Curcoy, A; Olsen, Rikke Katrine Jentoft; Ribes, A

    2003-01-01

    Multiple acyl-CoA-dehydrogenase deficiency (MADD) or glutaric aciduria type II (GAII) are a group of metabolic disorders due to deficiency of either electron transfer flavoprotein (ETF) or electron transfer flavoprotein ubiquinone oxidoreductase (ETF-QO). We report the clinical features...... and biochemical and molecular genetic analyses of a patient with a mild late-onset form of GAII due to beta-ETF deficiency. Biochemical data showed an abnormal urine organic acid profile, low levels of free carnitine, increased levels of C(10:1n-6), and C(14:1n-9) in plasma, and decreased oxidation of [9,10-3H......]palmitate and [9,10-3H]myristate in fibroblasts, suggesting MAD deficiency. In agreement with these findings, mutational analysis of the ETF/ETFDH genes demonstrated an ETFB missense mutation 124T>C in exon 2 leading to replacement of cysteine-42 with arginine (C42R), and a 604_606AAG deletion in exon 6...

  16. Primary antibody deficiencies at Queen Rania Children Hospital in Jordan: single center experience.

    Science.gov (United States)

    Habahbeh, Zeyad M; Abu-Shukair, Mohammad E; Almutereen, Mohammad A; Alzyoud, Raed M; Wahadneh, Adel M

    2014-03-01

    Primary antibody deficiency, the most common primary immunodeficiency disorder, represents a heterogeneous spectrum of conditions caused by a defect in any critical stage of B cell development and is characterized by impaired production of normal amounts of antigen-specific antibodies. This retrospective study aimed at description and analysis of demographic, clinical, immunological features and complications of subjects diagnosed with primary antibody deficiency at a referral center in Jordan. The medical records of pediatric patients who were diagnosed as primary antibody deficiency (PAD) during the period from January 2006 to June 2013 were reviewed. Patients were diagnosed as PADs based on the Pan-American Group for Immunodeficiency (PAGID) and the European Society for Immunodeficiency (ESID) diagnostic criteria. A total number of 53 patients with PAD were identified; 37(70%) males and 16(30%) females, 16(30%) patients with congenital agammaglobulinemia, 16(30%) patients with common variable immunodeficiency, 4(7.5%) patients with IgG subclass deficiency, 10(19%) cases with transient hypogammaglobulinemia of infancy and 7(13.5%) patients as undefined PAD. The most common infection among patients was pneumonia (62%); followed by suppurative otitis media in 49% of patients. Cytopenia was the most noted autoimmune association and was found at prevalence of 22 %, other autoimmune associations (17%) including inflammatory arthritis, discoid lupus, inflammatory bowel disease, vasculitis and celiac disease. The prevalence of long-term complications was 58%, the most frequent ones were; stunted growth in 13%, bronchiectasis and lymphoproliferation in 11% for each. Our results indicated that congenital agammaglobulinemia and common variable immunodeficiency are the most frequent primary antibody deficiency in our patients. The awareness of families, general population as well as primary health physicians is crucial in the establishment of early diagnosis and prompt

  17. Temporal Discrimination: Mechanisms and Relevance to Adult-Onset Dystonia

    Directory of Open Access Journals (Sweden)

    Antonella Conte

    2017-11-01

    Full Text Available Temporal discrimination is the ability to determine that two sequential sensory stimuli are separated in time. For any individual, the temporal discrimination threshold (TDT is the minimum interval at which paired sequential stimuli are perceived as being asynchronous; this can be assessed, with high test–retest and inter-rater reliability, using a simple psychophysical test. Temporal discrimination is disordered in a number of basal ganglia diseases including adult-onset dystonia, of which the two most common phenotypes are cervical dystonia and blepharospasm. The causes of adult-onset focal dystonia are unknown; genetic, epigenetic, and environmental factors are relevant. Abnormal TDTs in adult-onset dystonia are associated with structural and neurophysiological changes considered to reflect defective inhibitory interneuronal processing within a network which includes the superior colliculus, basal ganglia, and primary somatosensory cortex. It is hypothesized that abnormal temporal discrimination is a mediational endophenotype and, when present in unaffected relatives of patients with adult-onset dystonia, indicates non-manifesting gene carriage. Using the mediational endophenotype concept, etiological factors in adult-onset dystonia may be examined including (i the role of environmental exposures in disease penetrance and expression; (ii sexual dimorphism in sex ratios at age of onset; (iii the pathogenesis of non-motor symptoms of adult-onset dystonia; and (iv subcortical mechanisms in disease pathogenesis.

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

    Science.gov (United States)

    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.

  19. The evolution of radiation-induced growth hormone deficiency in adults is determined by the baseline growth hormone status

    Energy Technology Data Exchange (ETDEWEB)

    Toogood, A.A.; Ryder, W.D.J.; Beardwell, C.G.; Shalet, S.M. [Christie Hospital and Holt Radium Inst., Manchester (United Kingdom)

    1995-07-01

    Recent studies of GH replacement have suggested several beneficial effects for GH deficient adults. It would therefore be helpful to predict the time of onset of GH deficiency after external pituitary irradiation. We have studied the evolution of GH deficiency with time in patients irradiated for pituitary adenomas and other hypothalamic pituitary tumours. The results provide an insight into the pattern of the decline in GH secretion following radiotherapy in patients with pituitary disease and the factors affecting it. This information will help the clinician predict the frequency and timing of GH deficiency in patients irradiated for pituitary disease and the potential need for GH replacement therapy. (Author).

  20. Pathway discovery using transcriptomic profiles in adult-onset severe asthma

    DEFF Research Database (Denmark)

    Hekking, Pieter-Paul; Loza, Matt J; Pavlidis, Stelios

    2017-01-01

    in nasal brushings (5 signatures), sputum (3 signatures), and endobronchial brushings (6 signatures). Signatures associated with eosinophilic airway inflammation, mast cells, and group 3 innate lymphoid cells were more enriched in adult-onset severe asthma, whereas signatures associated with induced lung...... injury were less enriched in adult-onset severe asthma. CONCLUSIONS: Adult-onset severe asthma is characterized by inflammatory pathways involving eosinophils, mast cells, and group 3 innate lymphoid cells. These pathways could represent useful targets for the treatment of adult-onset severe asthma....

  1. Adult growth hormone deficiency

    Directory of Open Access Journals (Sweden)

    Vishal Gupta

    2011-01-01

    Full Text Available Adult growth hormone deficiency (AGHD is being recognized increasingly and has been thought to be associated with premature mortality. Pituitary tumors are the commonest cause for AGHD. Growth hormone deficiency (GHD has been associated with neuropsychiatric-cognitive, cardiovascular, neuromuscular, metabolic, and skeletal abnormalities. Most of these can be reversed with growth hormone therapy. The insulin tolerance test still remains the gold standard dynamic test to diagnose AGHD. Growth hormone is administered subcutaneously once a day, titrated to clinical symptoms, signs and IGF-1 (insulin like growth factor-1. It is generally well tolerated at the low-doses used in adults. Pegylated human growth hormone therapy is on the horizon, with a convenient once a week dosing.

  2. Latent Autoimmune Diabetes of the Adult (LADA in a Brazilian Indian

    Directory of Open Access Journals (Sweden)

    João Paulo Botelho Vieira Filho

    Full Text Available CONTEXT: Latent autoimmune diabetes of the adult (LADA as originally described represents perhaps as many as 10 -- 20% of adult-onset patients with diabetes. DESIGN: case report. CASE REPORT: A 38-year-old Brazilian Xavante-Jê Indian with Latent Autoimmune Diabetes of the Adult (LADA is described, coming from the Sangradouro community in Poxoréu, Mato Grosso. The onset of diabetes after reaching 25 years of age, the evolution to insulin deficiency after a period of insulin-independence and the presence of auto-antibodies to glutamic acid decarboxylase (GAD characteristic of LADA were present. This patient may represent the first case of LADA in a Brazilian with full Indian heritage. Further studies are necessary to verify the prevalence of this new type of diabetes in this population that does not have Caucasoid admixture and has a particular environmental background.

  3. Depression Risk in Young Adults With Juvenile- and Adult-Onset Lupus: Twelve Years of Followup.

    Science.gov (United States)

    Knight, Andrea M; Trupin, Laura; Katz, Patricia; Yelin, Edward; Lawson, Erica F

    2018-03-01

    To compare major depression risk among young adults with juvenile-onset and adult-onset systemic lupus erythematosus (SLE), and to determine demographic and health-related predictors of depression. Young adults with SLE ages 18-45 years (n = 546) in the Lupus Outcomes Study completed annual telephone surveys from 2002-2015, including assessment of depression using the Center for Epidemiologic Studies Depression Scale (CES-D), and self-report measures of sociodemographics and health characteristics. Juvenile-onset SLE was defined as age adult-onset SLE. Older age, lower educational attainment, and physical function, higher disease activity, and a history of smoking were associated with an increased depression risk. Juvenile-onset SLE patients had a higher risk of major depression across all educational groups. Young adults with SLE, particularly those with juvenile-onset disease, are at high risk for major depression, which is associated with increased disease activity, poorer physical functioning, and lower educational attainment. Early depression intervention in young adults with SLE has the potential to improve both medical and psychosocial outcomes. © 2017, American College of Rheumatology.

  4. Late-onset ornithine transcarbamylase deficiency: An under recognized cause of metabolic encephalopathy

    OpenAIRE

    Rush, Eric T; Hartmann, Julianne E; Skrabal, Jill C; Rizzo, William B

    2014-01-01

    Introduction: Ornithine transcarbamylase deficiency is the most common inherited disorder of the urea cycle, has a variable phenotype, and is caused by mutations in the OTC gene. We report three cases of ornithine transcarbamylase deficiency to illustrate the late-onset presentation of this disorder and provide strategies for diagnosis and treatment. The patients were maternal first cousins, presenting with hyperammonemia and obtundation. Urea cycle disorder was not initially suspected in the...

  5. Antigen-specific IgA titres after 23-valent pneumococcal vaccine indicate transient antibody deficiency disease in children

    NARCIS (Netherlands)

    Janssen, Willemijn J M; Nierkens, Stefan; Sanders, Elisabeth A; Boes, Marianne; van Montfrans, Joris M

    2015-01-01

    Paediatric patients with antibody deficiency may either be delayed in development of humoral immunity or may be persistently deficient in antibody production. To differentiate between these entities, we examined the 23-valent pneumococcal polysaccharide (PnPS) vaccine-induced IgM-, IgG- and IgA

  6. New-Onset Headache in Patients With Autoimmune Encephalitis Is Associated With anti-NMDA-Receptor Antibodies.

    Science.gov (United States)

    Schankin, Christoph J; Kästele, Fabian; Gerdes, Lisa Ann; Winkler, Tobias; Csanadi, Endy; Högen, Tobias; Pellkofer, Hannah; Paulus, Walter; Kümpfel, Tania; Straube, Andreas

    2016-06-01

    We tested the hypotheses (i) that autoimmune encephalitis is associated with new-onset headache, and (ii) that the occurrence of headache is associated with the presence of anti-N-methyl-D-aspartate (NMDA)-receptor antibodies. Autoimmune encephalitis presents with cognitive dysfunction as well as neuro-psychiatric symptoms. Its pathophysiology might involve antibody-mediated dysfunction of the glutamatergic system as indicated by the presence of anti-NMDA-receptor antibodies in some patients. In this cross-sectional study, patients with autoimmune encephalitis were assessed with a standardized interview for previous headache and headache associated with autoimmune encephalitis. Headache was classified according to the International Classification of Headache Disorders, second edition. Clinical and paraclinical findings were correlated with the occurrence of headache. Of 40 patients with autoimmune encephalitis, 19 did not have a history of headache. Of those, nine suffered from encephalitis-associated headache. Seven of these nine had anti-NMDA-receptor antibodies in contrast to only two among the remaining 10 patients without new-onset headache (P = .023, odds ratio: 14, 95% confidence interval: 1.5; 127). In most patients headache occurred in attacks on more than 15 days/month, was severe, and of short duration (less than 4 hours). International Headache Society criteria for migraine were met in three patients. New-onset headache is a relevant symptom in patients with autoimmune encephalitis who have no history of previous headache, especially in the subgroup with anti-NMDA-receptor antibodies. This indicates a thorough investigation for secondary headaches including anti-NMDA-R antibodies for patients with new-onset headache and neuropsychiatric findings. Glutamatergic dysfunction might be important for the generation of head pain but may only occasionally be sufficient to trigger migraine-like attacks in nonmigraineurs. © 2016 American Headache Society.

  7. Guanidinoacetate methyltransferase (GAMT) deficiency: late onset of movement disorder and preserved expressive language.

    Science.gov (United States)

    O'Rourke, Declan J; Ryan, Stephanie; Salomons, Gajja; Jakobs, Cornelis; Monavari, Ahmad; King, Mary D

    2009-05-01

    Guanidinoacetate methyltransferase (GAMT) deficiency is a disorder of creatine biosynthesis, characterized by early-onset learning disability and epilepsy in most affected children. Severe expressive language delay is a constant feature even in the mildest clinical phenotypes.We report the clinical, biochemical, imaging, and treatment data of two female siblings (18y and 13y) with an unusual phenotype of GAMT deficiency. The oldest sibling had subacute onset of a movement disorder at age 17 years, later than has been previously reported. The younger sibling had better language skills than previously described in this disorder. After treatment with creatine, arginine restriction and ornithine-supplemented diet, seizure severity and movement disorder were reduced but cognition did not improve. This report confirms that GAMT deficiency, a heterogeneous, potentially treatable disorder, detected by increased levels of guanidinoacetate in body fluids (e.g. plasma or urine) or by an abnormal creatine peak on magnetic resonance spectroscopy, should be considered in patients of any age with unexplained, apparently static learning disability and epilepsy.

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

    Directory of Open Access Journals (Sweden)

    Fereshteh Ashtari

    2010-01-01

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

  9. The diagnostic challenge of Adult-onset Still's disease | Rostamipour ...

    African Journals Online (AJOL)

    The diagnostic challenge of Adult-onset Still's disease. ... Elevated serum ferritin level is not yet considered as a criteria for diagnosis of AOSD in Yamaguchi criteria, however, there are several studies which have demonstrated a strong ... Keywords: Adult Onset Still's Disease; Fever of Unknown Origin, serum ferritin ...

  10. Rest tremor in idiopathic adult-onset dystonia.

    Science.gov (United States)

    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.

  11. Adult-onset nemaline myopathy presenting as respiratory failure.

    LENUS (Irish Health Repository)

    Kelly, Emer

    2008-11-01

    Nemaline myopathy is a rare congenital myopathy that generally presents in childhood. We report a case of a 44-year-old man who presented with severe hypoxic hypercapnic respiratory failure as the initial manifestation of nemaline myopathy. After starting noninvasive ventilation, his pulmonary function test results improved substantially, and over the 4 years since diagnosis his respiratory function remained stable. There are few reported cases of respiratory failure in patients with adult-onset nemaline myopathy, and the insidious onset in this case is even more unusual. This case highlights the varied presenting features of adult-onset nemaline myopathy and that noninvasive ventilation improves respiratory function.

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

    Science.gov (United States)

    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 (Pactivities (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.

  13. Late-onset ornithine transcarbamylase deficiency: An under recognized cause of metabolic encephalopathy

    Directory of Open Access Journals (Sweden)

    Eric T Rush

    2014-07-01

    Full Text Available Introduction: Ornithine transcarbamylase deficiency is the most common inherited disorder of the urea cycle, has a variable phenotype, and is caused by mutations in the OTC gene. We report three cases of ornithine transcarbamylase deficiency to illustrate the late-onset presentation of this disorder and provide strategies for diagnosis and treatment. The patients were maternal first cousins, presenting with hyperammonemia and obtundation. Urea cycle disorder was not initially suspected in the first patient, delaying diagnosis. Results: Sequencing of the OTC gene showed a novel missense mutation, c.563G > C (p.G188A. Numerous family members were found to carry this mutation, which shows a trend toward later onset. Each urea cycle disorder has its own unique pattern of biochemical abnormalities, which differ from non-metabolic causes of critical illness. Conclusion: Regardless of age, clinical suspicion of a urea cycle disorder is important in encephalopathic patients to ensure quick diagnosis and definitive treatment of the underlying inborn error of metabolism.

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

    Science.gov (United States)

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

    2015-01-01

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

  15. Differences between asthma-COPD overlap syndrome and adult-onset asthma.

    Science.gov (United States)

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

    2017-05-01

    Differences between asthma-COPD overlap syndrome (ACOS) and adult-onset asthma are poorly understood. This study aimed to evaluate these differences in a clinical cohort of patients with adult-onset asthma, as a part of the Seinäjoki Adult Asthma Study (SAAS).188 patients were diagnosed with adult-onset asthma and re-evaluated 12 years after diagnosis. They were divided into three groups based on smoking history and post bronchodilator spirometry values: 1) never- and ex-smokers with obstructive (forced expiratory volume in 1 s (FEV 1 )/forced vital capacity (FVC) ≥0.7) patients with ≥10 pack-years; and 3) ACOS patients with ≥10 pack-years and FEV 1 /FVC obstructive patients with ≥10 pack-years smoking history, respectively. ACOS patients also showed reduced lung function, higher remaining bronchial reversibility and a higher number of comorbidities.This study shows distinct differences in diffusing capacity, blood neutrophil and IL-6 levels, bronchial reversibility, lung function and comorbidities between ACOS and adult-onset asthma. The present findings should be considered in the comprehensive assessment of adult asthma patients. Copyright ©ERS 2017.

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

    Science.gov (United States)

    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.

  17. Adult Onset Still's Disease and Rocky Mountain Spotted Fever

    Directory of Open Access Journals (Sweden)

    Paul Persad

    2010-01-01

    Full Text Available Adult Still's Disease was first described in 1971 by Bywaters in fourteen adult female patients who presented with symptoms indistinguishable from that of classic childhood Still's Disease (Bywaters, 1971. George Still in 1896 first recognized this triad of quotidian (daily fevers, evanescent rash, and arthritis in children with what later became known as juvenile inflammatory arthritis (Still, 1990. Adult Onset Still's Disease (AOSD is an inflammatory condition of unknown etiology characterized by an evanescent rash, quotidian fevers, and arthralgias. Numerous infectious agents have been associated with its presentation. This case is to our knowledge the first presentation of AOSD in the setting of Rocky Mountain Spotted Fever. Although numerous infectious agents have been suggested, the etiology of this disorder remains elusive. Nevertheless, infection may in fact play a role in triggering the onset of symptoms in those with this disorder. Our case presentation is, to our knowledge, the first case of Adult Onset Still's Disease associated with Rocky Mountain spotted fever (RMSF.

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

    Science.gov (United States)

    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.

  19. Unusual radiological findings of adult-onset pulmonary tuberculosis

    International Nuclear Information System (INIS)

    Lee, Yong Chul; Lee, Jong Beum; Kim, Sue Hyun

    1987-01-01

    Usual chest radiographic findings in pulmonary tuberculosis are well described in radiologic literatures for both primary and postprimary phases of disease. During the last decade, many authors have enumerated the unusual manifestations of pulmonary tuberculosis in adult population. These unusual findings usually have been involved in the frequent failure of both radiologist and clinician to recognize that tuberculosis could be the cause of a abnormal chest radiograph in patients who are finally and surprisingly proven to have tuberculosis. Authors have evaluated 249 patients who were admitted and newly proven to have adult-onset pulmonary tuberculosis at Chung-Ang University Hospital from January, 1985 to December, 1986. Unusual findings were noted in 76 (30.5%) of the 249 patients with adult-onset pulmonary tuberculosis. These unusual findings most frequently could be seen in 3rd decades and showed no sex difference in incidence. A broad spectrum of abnormal findings including usual and unusual abnormalities were procedure by adult-onset pulmonary tuberculosis. The unusual radiographic findings were arbitrarily classified. Pleural effusion without parenchymal disease (10.0%), unusual location of infiltrate (5.6%) and atelectasis (3.2%) were relatively common. Hilar and / or mediastinal lymphnode enlargement (1.6%), cavity without parenchymal infiltrates (1.6%), septic lung-like infiltrates (1.6%), completely clear lungs (1.2%), miliary infiltrates (1.2%), fibrocalcific scar-like infiltrates (1.2%), masslike density (1.2%) and rheumatoid lung-like infiltrates (1.2%) were occasionally noted. Pneumothorax without parenchymal disease (0.4%) and bron chocutaneous fistula (0.4%) are. The recognition of these unusual findings could further improve the detection and diagnosis of adult-onset pulmonary tuberculosis

  20. Successful Treatment of Adult-Onset Erythromelalgia with Steroid Pulse and Pregabalin

    Directory of Open Access Journals (Sweden)

    Aya Kakizaki

    2012-11-01

    Full Text Available Adult-onset erythromelalgia (EM is a rare disease characterized by episodic bouts of burning pain and erythema for which the optimal therapy is unclear. In this report, we describe a 68-year-old Japanese woman with adult-onset EM. Intravenous administration of methylprednisolone sodium succinate 1,000 mg/day dramatically improved her pain as evaluated by the visual analog scale. Although the patient’s pain gradually developed again, it could be controlled with pregabalin. Our present case might suggest a possible, optimal therapy for adult-onset EM.

  1. Retrospective natural history of thymidine kinase 2 deficiency.

    Science.gov (United States)

    Garone, Caterina; Taylor, Robert W; Nascimento, Andrés; Poulton, Joanna; Fratter, Carl; Domínguez-González, Cristina; Evans, Julie C; Loos, Mariana; Isohanni, Pirjo; Suomalainen, Anu; Ram, Dipak; Hughes, M Imelda; McFarland, Robert; Barca, Emanuele; Lopez Gomez, Carlos; Jayawant, Sandeep; Thomas, Neil D; Manzur, Adnan Y; Kleinsteuber, Karin; Martin, Miguel A; Kerr, Timothy; Gorman, Grainne S; Sommerville, Ewen W; Chinnery, Patrick F; Hofer, Monika; Karch, Christoph; Ralph, Jeffrey; Cámara, Yolanda; Madruga-Garrido, Marcos; Domínguez-Carral, Jana; Ortez, Carlos; Emperador, Sonia; Montoya, Julio; Chakrapani, Anupam; Kriger, Joshua F; Schoenaker, Robert; Levin, Bruce; Thompson, John L P; Long, Yuelin; Rahman, Shamima; Donati, Maria Alice; DiMauro, Salvatore; Hirano, Michio

    2018-03-30

    Thymine kinase 2 (TK2) is a mitochondrial matrix protein encoded in nuclear DNA and phosphorylates the pyrimidine nucleosides: thymidine and deoxycytidine. Autosomal recessive TK2 mutations cause a spectrum of disease from infantile onset to adult onset manifesting primarily as myopathy. To perform a retrospective natural history study of a large cohort of patients with TK2 deficiency. The study was conducted by 42 investigators across 31 academic medical centres. We identified 92 patients with genetically confirmed diagnoses of TK2 deficiency: 67 from literature review and 25 unreported cases. Based on clinical and molecular genetics findings, we recognised three phenotypes with divergent survival: (1) infantile-onset myopathy (42.4%) with severe mitochondrial DNA (mtDNA) depletion, frequent neurological involvement and rapid progression to early mortality (median post-onset survival (POS) 1.00, CI 0.58 to 2.33 years); (2) childhood-onset myopathy (40.2%) with mtDNA depletion, moderate-to-severe progression of generalised weakness and median POS at least 13 years; and (3) late-onset myopathy (17.4%) with mild limb weakness at onset and slow progression to respiratory insufficiency with median POS of 23 years. Ophthalmoparesis and facial weakness are frequent in adults. Muscle biopsies show multiple mtDNA deletions often with mtDNA depletion. In TK2 deficiency, age at onset, rate of weakness progression and POS are important variables that define three clinical subtypes. Nervous system involvement often complicates the clinical course of the infantile-onset form while extraocular muscle and facial involvement are characteristic of the late-onset form. Our observations provide essential information for planning future clinical trials in this disorder. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  2. Antibody-based inhibition of circulating DLK1 protects from estrogen deficiency-induced bone loss in mice

    DEFF Research Database (Denmark)

    Figeac, Florence; Andersen, Ditte C.; Nipper Nielsen, Casper A.

    2018-01-01

    /TV) and inhibition of bone resorption. No significant changes were observed in total fat mass or in the number of bone marrow adipocytes. These results support the potential use of anti-DLK1 antibody therapy as a novel intervention to protect from E deficiency associated bone loss....... resorption and inhibition of bone formation. Further, serum DLK1 levels are elevated and positively correlated to bone turnover markers in estrogen (E)-deficient rodents and women. In this report, we examined whether inhibition of serum DLK1 activity using a neutralizing monoclonal antibody protects from E...

  3. Adult-onset Rasmussen encephalitis associated with focal cortical dysplasia.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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 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.

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

    Science.gov (United States)

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

    2018-04-04

    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 N-terminally truncated GAD65 autoantibodies is associated with the clinical phenotype of autoimmune type 1 diabetes and predicts insulin therapy.

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

    Directory of Open Access Journals (Sweden)

    Hsu-Sheng Yu

    2016-12-01

    Full Text Available 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.

  7. A comparison between nailfold capillaroscopy patterns in adulthood in juvenile and adult-onset systemic sclerosis

    DEFF Research Database (Denmark)

    Ingegnoli, Francesca; Boracchi, Patrizia; Gualtierotti, Roberta

    2015-01-01

    OBJECTIVE: 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. METHODS: Data collected between June 2004 and April 2013 were examined with focus on capillar......OBJECTIVE: 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. METHODS: 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. RESULTS: 30 of 123 patients with juvenile-onset and 2108 of 7133 with adult-onset SSc had data on capillaroscopy...... in 61% of juvenile- and 55.5% of adult-onset SSc. The OR was 1.06 and 95% CI 0.34-3.56. CONCLUSION: 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...

  8. Bone Mineral Density and Body Composition in Adolescents with Childhood-Onset Growth Hormone Deficiency

    NARCIS (Netherlands)

    Boot, Annemieke M.; van der Sluis, Inge M.; Krenning, Eric P.; Keizer-Schrama, Sabine M. P. F. de Muinck

    2009-01-01

    Background/Aims: The aim of the present study was to evaluate bone mineral density (BMD) and body composition of patients with childhood-onset growth hormone (GH) deficiency (GHD) treated with GH during the transition period. Methods: BMD and body composition, measured by dual-energy X-ray

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

    NARCIS (Netherlands)

    Silove, Derrick; Alonso, Jordi; Bromet, Evelyn; Gruber, Mike; Sampson, Nancy; Scott, Kate; Andrade, Laura; Benjet, Corina; Caldas de Almeida, Jose Miguel; 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.

    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

  10. Does the Maternal Serum IgG Level during Pregnancy in Primary Antibody Deficiency Influence the IgG Level in the Newborn?

    Directory of Open Access Journals (Sweden)

    Vasantha Nagendran

    2015-01-01

    Full Text Available Purpose. To find out if the serum IgG level in the newborn baby was affected by low maternal serum IgG during pregnancy in two newly diagnosed primary antibody deficient patients. Method. Infant cord blood IgG level was compared with maternal IgG level in 2 mothers with newly diagnosed primary antibody deficiency, who declined replacement IgG treatment during pregnancy. Results. Both mothers delivered healthy babies with normal IgG levels at birth. Conclusions. The normal IgG levels and sound health in these 2 babies in spite of low maternal IgG throughout pregnancy raise interesting discussion points about maternofoetal immunoglobulin transport mechanisms in primary antibody deficiency.

  11. Tandem mass spectrometry, but not T-cell receptor excision circle analysis, identifies newborns with late-onset adenosine deaminase deficiency.

    Science.gov (United States)

    la Marca, Giancarlo; Canessa, Clementina; Giocaliere, Elisa; Romano, Francesca; Duse, Marzia; Malvagia, Sabrina; Lippi, Francesca; Funghini, Silvia; Bianchi, Leila; Della Bona, Maria Luisa; Valleriani, Claudia; Ombrone, Daniela; Moriondo, Maria; Villanelli, Fabio; Speckmann, Carsten; Adams, Stuart; Gaspar, Bobby H; Hershfield, Michael; Santisteban, Ines; Fairbanks, Lynette; Ragusa, Giovanni; Resti, Massimo; de Martino, Maurizio; Guerrini, Renzo; Azzari, Chiara

    2013-06-01

    Adenosine deaminase (ADA)-severe combined immunodeficiency (SCID) is caused by genetic variants that disrupt the function of ADA. In its early-onset form, it is rapidly fatal to infants. Delayed or late-onset ADA-SCID is characterized by insidious progressive immunodeficiency that leads to permanent organ damage or death. Quantification of T-cell receptor excision circles (TRECs) or tandem mass spectrometry (tandem-MS) analysis of dried blood spots (DBSs) collected at birth can identify newborns with early-onset ADA-SCID and are used in screening programs. However, it is not clear whether these analyses can identify newborns who will have delayed or late-onset ADA-SCID before symptoms appear. We performed a retrospective study to evaluate whether tandem-MS and quantitative TREC analyses of DBSs could identify newborns who had delayed-onset ADA-SCID later in life. We tested stored DBSs collected at birth from 3 patients with delayed-onset ADA-SCID using tandem-MS (PCT EP2010/070517) to evaluate levels of adenosine and 2'-deoxyadenosine and real-time PCR to quantify TREC levels. We also analyzed DBSs from 3 newborns with early-onset ADA-SCID and 2 healthy newborn carriers of ADA deficiency. The DBSs taken at birth from the 3 patients with delayed-onset ADA-SCID had adenosine levels of 10, 25, and 19 μmol/L (normal value, <1.5 μmol/L) and 2'-deoxyadenosine levels of 0.7, 2.7, and 2.4 μmol/L (normal value, <0.07 μmol/L); the mean levels of adenosine and 2'-deoxyadenosine were respectively 12.0- and 27.6-fold higher than normal values. DBSs taken at birth from all 3 patients with delayed-onset ADA deficiency had normal TREC levels, but TRECs were undetectable in blood samples taken from the same patients at the time of diagnosis. Tandem-MS but not TREC quantification identifies newborns with delayed- or late-onset ADA deficiency. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

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

    Science.gov (United States)

    LaPlante, Mitchell P

    2014-01-01

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

  13. Tocilizumab-Induced Acute Liver Injury in Adult Onset Still’s Disease

    Directory of Open Access Journals (Sweden)

    Michael Drepper

    2013-01-01

    Full Text Available Background. Tocilizumab, a monoclonal humanized anti-IL-6 receptor antibody, is used in treatment of refractory adult onset Still’s disease (AOSD. Mild to moderate liver enzyme elevation is a well-known side effect, but severe liver injury has only been reported in 3 cases in the literature. Case. A young female suffering from corticoid and methotrexate refractory AOSD was treated by tocilizumab. After 19 months of consecutive treatment, she developed acute severe liver injury. Liver biopsy showed extensive hepatocellular necrosis with ballooned hepatocytes, highly suggestive of drug-induced liver injury. No other relevant drug exposure beside tocilizumab was recorded. She recovered totally after treatment discontinuation and an initial 3-day course of intravenous N-acetylcysteine with normalization of liver function tests after 6 weeks. Conclusion. Acute severe hepatitis can be associated with tocilizumab as documented in this case. Careful monitoring of liver function tests is warranted during tocilizumab treatment.

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

    OpenAIRE

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

    2000-01-01

    BACKGROUND—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 whee...

  15. Persistent HIV antigenaemia and decline of HIV core antibodies associated with transition to AIDS

    NARCIS (Netherlands)

    Lange, J. M.; Paul, D. A.; Huisman, H. G.; de Wolf, F.; van den Berg, H.; Coutinho, R. A.; Danner, S. A.; van der Noordaa, J.; Goudsmit, J.

    1986-01-01

    Sequential serum samples from 13 homosexual men who seroconverted for antibodies to human immunodeficiency virus (HIV) were tested for HIV antigen. In one of these men, who developed the acquired immune deficiency syndrome (AIDS), HIV antigenaemia preceded the onset of AIDS by more than a year and

  16. Hypothyroidism in late-onset Pompe disease.

    Science.gov (United States)

    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 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.

  17. A rare case of Addison's disease, hepatitis, thyreoiditis, positive IgG anti-tissue transglutaminase antibodies and partial IgA deficiency.

    Science.gov (United States)

    Baleva, Marta P; Mihaylova, Snejina; Yankova, Petja; Atanasova, Iliana; Nikolova-Vlahova, Milena; Naumova, Elissaveta

    2016-01-01

    Selective IgA deficiency (IgAD) is the most prevalent type of primary immune deficiencies, but partial IgA deficiency is even more common. Addison's disease is a rare condition associated with primary adrenal insufficiency due to infection or autoimmune destruction of the adrenals. The association between IgA deficiency and Addison's disease is very rare. We observed a 22-year-old male patient with marked darkening of the skin, especially on the palms and areolae, jaundice on the skin and sclera, astheno-adynamia, hypotension (80/50 mm Hg), and pain in the right hypochondrium. The laboratory investigations revealed increased serum levels of total and indirect bilirubin, AST, ALT, GGT and LDH, negative HBsAg, anti-HBc IgM, anti-HCV and anti-HAV IgM, very low serum IgA levels (0.16 g/l) with normal IgG and IgM, negative ANA, ANCA, AMA, LKM-1, anti-GAD-60, anti-IA-2, anti-thyroglobulin antibodies, a mild increase in anti-TPO antibodies titer, a marked increase in IgG anti-tissue transglutaminase antibodies, with no typical changes in cellular immunity, negative T-SPOT-TB test, HLA - A*01; B*08; DRB1*03; DQB1*02, karyotype - 46, XY. We present a rare case of partial IgA deficiency with Addison's disease, hepatitis, thyroiditis and positive anti-tissue transglutaminase antibodies. IgAD and some autoimmune disorders share several predisposing HLA genes, thus explaining the increased prevalence of IgAD in certain patient groups.

  18. Semen quality in patients with pituitary disease and adult-onset hypogonadotropic hypogonadism

    DEFF Research Database (Denmark)

    Andreassen, Mikkel; Juul, Anders; Feldt-Rasmussen, Ulla

    2018-01-01

    with adult-onset gonadotropin insufficiency. DESIGN AND METHODS: A retrospective study comprising 20 testosterone-deficient men (median age, 29 years) with acquired pituitary disease who delivered semen for cryopreservation before initiation of testosterone therapy. Semen variables and hormone concentrations...... (median (intraquartile range) 3.0 (1.3-6.8) vs 3.2 (2.3-4.3) mL, P = 0.47), sperm concentration 41 (11-71) vs 43 (22-73) mill/mL (P = 0.56) or total sperm counts (P = 0.66). One patient had azoospermia. Patients vs controls had lower serum testosterone 5.4 (2.2-7.6) vs 19.7 (15.5-24.5) nmol/L (P = 0.......001), calculated free testosterone (cfT) 145 (56-183) vs 464 (359-574) pmol/L (P 3.1 (2.3-4.0) U/L (P = 0.002) and inhibin b (P 

  19. Long-term deficiency of circulating and hippocampal insulin-like growth factor I induces depressive behavior in adult mice: A potential model of geriatric depression

    Science.gov (United States)

    Mitschelen, Matthew; Yan, Han; Farley, Julie A.; Warrington, Junie P.; Han, Song; Hereñú, Claudia B.; Csiszar, Anna; Ungvari, Zoltan; Bailey-Downs, Lora C.; Bass, Caroline E.; Sonntag, William E.

    2011-01-01

    Numerous studies support the hypothesis that deficiency of insulin-like growth factor I (IGF-1) in adults contributes to depression, but direct evidence is limited. Many psychological and pro-cognitive effects have been attributed to IGF-1, but appropriate animal models of adult-onset IGF-1 deficiency are lacking. In this study, we use a viral-mediated Cre-loxP system to knockout the Igf1 gene in either the liver, neurons of the CA1 region of the hippocampus, or both. Knockout of liver Igf1 reduced serum IGF-1 levels by 40% and hippocampal IGF-1 levels by 26%. Knockout of Igf1 in CA1 reduced hippocampal IGF-1 levels by 13%. The most severe reduction in hippocampal IGF-1 occurred in the group with knockouts in both liver and CA1 (36% reduction), and was associated with a 3.5-fold increase in immobility in the forced swim test. Reduction of either circulating or hippocampal IGF-1 levels did not alter anxiety measured in an open field and elevated plus maze, nor locomotion in the open field. Furthermore, local compensation for deficiencies in circulating IGF-1 did not occur in the hippocampus, nor were serum levels of IGF-1 upregulated in response to the moderate decline of hippocampal IGF-1 caused by the knockouts in CA1. We conclude that adult-onset IGF-1 deficiency alone is sufficient to induce a depressive phenotype in mice. Furthermore, our results suggest that individuals with low brain levels of IGF-1 are at increased risk for depression and these behavioral effects are not ameliorated by increased local IGF-1 production or transport. Our study supports the hypothesis that the natural IGF-1 decline in aging humans may contribute to geriatric depression. PMID:21524689

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

    Science.gov (United States)

    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 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 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 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.

  1. Caspase-8 Deficiency Presenting as Late-Onset Multi-Organ Lymphocytic Infiltration with Granulomas in two Adult Siblings.

    Science.gov (United States)

    Niemela, Julie; Kuehn, Hye Sun; Kelly, Corin; Zhang, Mingchang; Davies, Joie; Melendez, Jose; Dreiling, Jennifer; Kleiner, David; Calvo, Katherine; Oliveira, João B; Rosenzweig, Sergio D

    2015-05-01

    Caspase-8 deficiency (CED) was originally described in 2002 in two pediatric patients presenting with clinical manifestations resembling autoimmune lymphoproliferative syndrome (ALPS) accompanied by infections, and T, B and NK cell defects. Since then, no new CED patients were published. Here we report two adult siblings (Pt1 and Pt2) presenting in their late thirties with pulmonary hypertension leading to lung transplant (Pt1), and a complex neurological disease leading to multiple cranial nerves palsies (Pt2) as their main manifestations. A thorough clinical and immunological evaluation was performed at the Primary Immunodeficiency Clinic at NIH, followed by whole exome sequencing. The patients had multiorgan lymphocytic infiltration and granulomas, as well as clinical signs of immune deficiency/ immune dysregulation. Both siblings carried homozygous mutations in CASP8, c.1096C > T, p.248R > W. This was the same mutation described on the previously published CED patients, to whom these new patients were likely distantly related. We report two new CED patients presenting during adulthood with life-threatening end-organ lymphocyte infiltrates affecting the lungs, liver, spleen, bone marrow and central nervous system. This phenotype broadens the clinical spectrum of manifestations associated with this disease and warrants the search of CASP8 mutations in other cohorts of patients.

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

    Science.gov (United States)

    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.

  3. The experience of living with adult-onset epilepsy.

    Science.gov (United States)

    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.

  4. Morbidity and GH deficiency: a nationwide study

    DEFF Research Database (Denmark)

    Stochholm, K.; Laursen, T.; Green, A.

    2008-01-01

    identified in the National Patient Registry. Lag time until first admission was used as a measure of morbidity. Patients were divided into childhood onset (CO) and adult onset (AO), discriminated by an age cut-off of 18 years at onset of GHD. Method: Sex- and cause-specific hazard ratios (HRs) in CO and AO......Objective: To estimate morbidity in Denmark in all patients with GH deficiency (GHD). Design: Morbidity was analyzed in 1794 GHD patients and 8014 controls matched on age and gender. All records in the GHD patients were studied and additional morbidity noted. Diagnoses and dates of admissions were...

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

    Science.gov (United States)

    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.

  6. Adult-onset epilepsy in focal cortical dysplasia of Taylor type

    NARCIS (Netherlands)

    Siegel, A. M.; Cascino, G. D.; Elger, C. E.; Devinsky, O.; Laff, R.; Najjar, S.; Sperling, M. R.; LoRusso, G.; Cossu, M.; Urbach, H.; Aronica, E.; Meyer, F. B.; Scheithauer, B. W.; Dubeau, F.; Andermann, F.

    2005-01-01

    Focal cortical dysplasia of Taylor type (FCDT) usually presents with seizures at an early age, whereas adult onset of epilepsy is uncommon. We reviewed the medical records of 213 patients with FCDT. In 21 patients (10%), age at seizure onset ranged from 18 to 55 years (mean 25.3). The outcome of

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

    Science.gov (United States)

    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.

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

    LENUS (Irish Health Repository)

    Kimmich, Okka

    2012-02-01

    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.

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

    Science.gov (United States)

    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), 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.

  10. Isotypic analysis of antibodies against activated Factor VII in patients with Factor VII deficiency using the x-MAP technology.

    Science.gov (United States)

    Pfeiffer, Caroline; Mathieu-Dupas, Eve; Logghe, Pauline; Lissalde-Lavigne, Géraldine; Balicchi, Julien; Caliskan, Umran; Valentin, Thomas; Laune, Daniel; Molina, Franck; Schved, Jean François; Giansily-Blaizot, Muriel

    2016-05-01

    While the immune response to hemophilic factors in hemophilia has been widely studied, little is known about the development of anti-Factor VII (FVII) antibodies in FVII deficiency. We developed a robust technique based on the x-MAP technology to detect the presence of antibodies against FVII and characterize their isotype and validated this method using blood samples from 100 patients with FVII deficiency (median FVII clotting activity [FVII:C]: 6%) and 95 healthy controls. Anti-FVII antibodies were detected in patients but also in some controls, although the concentration of total immunoglobulin G (IgGt) and IgG1 and IgG4 subclasses was significantly different between groups. The IgG1 subclass concentrations remained significantly different also when only untreated patients were compared with controls. This difference could partially be related to the F7 genotype, particularly in patients harboring the p.Arg139Gln mutation. This x-MAP-based method might be useful for assessing the immunogenicity of novel FVII compounds and of activated FVII (FVIIa) concentrates. Further prospective studies are needed to better understand the clinical relevance of these antibodies in the management of patients with FVII deficiency. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Stress and Disease Onset in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

    Directory of Open Access Journals (Sweden)

    Christina V. Golemati

    2017-12-01

    Full Text Available ObjectiveTo explore the potential contribution of stress as a trigger for disease onset in patients with antineutrophil cytoplasmic antibody (ANCA associated vasculitis (AAV.Methods53 AAV and 85 rheumatoid arthritis (RA patients as well as 53 healthy controls (HC were thoroughly asked for the number and impact of stressful life events, coping strategies, and available social support 12 months prior to disease onset. Anxiety, depression, personality dimensions, insomnia, and fatigue were also determined.ResultsAAV patients reported higher scoring of the impact of stressful life events compared to the RA and HC group prior to disease onset (2.8 ± 3.1 vs 1.8 ± 2.1 vs 1.7 ± 2.3, p-values: 0.047 and 0.053, respectively. While the number of reported stressful events was found to be significantly higher in AAV vs RA patients but not HC, certain coping strategies and social support features were more commonly implemented by AAV patients compared to HC, but not RA patients. As far as personality and other psychosocial characteristics, AAV patients displayed significantly higher psychoticism traits compared to RA, with no other differences being detected between AAV patients and both RA and HC. After adjusting for potential cofounders, scoring of the impact of stressful life events >3 was independently associated with AAV development compared to both RA and HC [ORs (95% CI: 4.6 (1.6–13.4 and 4.4 (1.0–19.0, respectively].ConclusionThe perceived impact of stressful life events prior to disease onset emerged as a contributing factor for AAV development.

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

    Science.gov (United States)

    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

  13. Association between l-thyroxine treatment, GH deficiency, and radiological vertebral fractures in patients with adult-onset hypopituitarism.

    Science.gov (United States)

    Mazziotti, G; Mormando, M; Cristiano, A; Bianchi, A; Porcelli, T; Giampietro, A; Maffezzoni, F; Serra, V; De Marinis, L; Giustina, A

    2014-06-01

    In this study, we aimed at evaluating the association between radiological vertebral fractures and levo-thyroxine (l-T4) replacement doses in adult patients with hypopituitarism. Cross-sectional study. We studied 74 adult hypopituitary patients (males, 43; females, 31; mean age, 57 years; and range, 23-79) with central hypothyroidism treated with l-T4 (median daily dose: 1.1  μg/kg). All patients also had severe GH deficiency (GHD) and 38 of them were replaced with recombinant GH. Vertebral fractures were assessed by a quantitative morphometric analysis performed on thoracic and lumbar spine lateral X-ray. Radiological vertebral fractures were found in 23 patients (31.1%) in association with untreated GHD (P=0.02), higher serum free T4 levels (P=0.03), a higher daily dose of l-T4 (P=0.005), and a longer duration of hypopituitarism (P=0.05). When GHD was treated, the prevalence of vertebral fractures was more frequent (P=0.03) in patients receiving high l-T4 doses (third tertile: >1.35  μg/kg per day) as compared with patients who were treated with lower drug doses (first tertile: hypopituitarism. © 2014 European Society of Endocrinology.

  14. Multiple endocrinopathies (growth hormone deficiency, autoimmune hypothyroidism and diabetes mellitus in Kearns-Sayre syndrome

    Directory of Open Access Journals (Sweden)

    A. Berio

    2013-06-01

    Full Text Available Kearns-Sayre syndrome is characterized by onset before 20 years, chronic progressive external opthalmoplegia, pigmentary retinal degeneration, and ataxia (and/or hearth block, and/or high protein content in the cerebrospinal fluid in the presence of mtDNA rearrangements. Multiple endocrine dysfunction associated with this syndrome was rarely reported. In this paper, the Authors report on a female patient with Kearns-Sayre syndrome with large heteroplasmic mtDNA deletion, absence of cytochrome c oxidase in many muscle fibers, partial GH deficiency, hypothyroidism and subsequently insulin dependent diabetes mellitus (IDDM. Anti-thyroid peroxidase and antithyreoglobulin antibodies were present in high titer in serum while anti-islet cell antibodies were absent. The patient developed thyroiditis with Hashimoto encephalopathy. The presence of GH deficiency, autoimmune thyroiditis with hypothyroidism and IDDM distinguishes this case from others and confirms the association of Kearns-Sayre syndrome with multiple endocrine dysfunction. Hashimoto encephalopathy and anti-thyroideal antibodies suggest that in this patient, predisposed by a genetic factor (a mitochondrial deletion anti-thyroideal antibodies may have contributed to the hypothyroidism and, by interfering with cerebral mitochondrial function, may have caused the encephalopathy. GH deficiency and IDDM can be attributed to oxidative phosphorylation deficiency but the autoimmunity may also have played a role in the production of glandular insufficiencies. It seems important to search for endocrine autoimmunity in every case of KSS.

  15. 29 French adult patients with PMM2-congenital disorder of glycosylation: outcome of the classical pediatric phenotype and depiction of a late-onset phenotype.

    Science.gov (United States)

    Monin, Marie-Lorraine; Mignot, Cyril; De Lonlay, Pascale; Héron, Bénédicte; Masurel, Alice; Mathieu-Dramard, Michèle; Lenaerts, Catherine; Thauvin, Christel; Gérard, Marion; Roze, Emmanuel; Jacquette, Aurélia; Charles, Perrine; de Baracé, Claire; Drouin-Garraud, Valérie; Khau Van Kien, Philippe; Cormier-Daire, Valérie; Mayer, Michèle; Ogier, Hélène; Brice, Alexis; Seta, Nathalie; Héron, Delphine

    2014-12-11

    PMM2-CDG (formerly known as CDG Ia) a deficiency in phosphomannomutase, is the most frequent congenital disorder of glycosylation. The phenotype encompasses a wide range of neurological and non-neurological manifestations comprising cerebellar atrophy and intellectual deficiency. The phenotype of the disorder is well characterized in children but the long term course of the disease is unknown and the phenotype of late onset forms has not been comprehensively described. We thus retrospectively collected the clinical, biological and radiological data of 29 French PMM2-CDG patients aged 15 years or more with a proven molecular diagnosis (16 females and 13 males). In addition, thirteen of these patients were reexamined at the time of the study to obtain detailed information. 27 of the 29 patients had a typical PMM2-CDG phenotype, with infantile hypotonia, strabismus, developmental delay followed by intellectual deficiency, epilepsy, retinitis pigmentosa and/or visceral manifestations. The main health problems for these patients as teenagers and in adulthood were primary ovarian insufficiency, growth retardation, coagulation anomalies and thrombotic events, skeletal deformities and osteopenia/osteoporosis, retinitis pigmentosa, as well as peripheral neuropathy. Three patients had never walked and three lost their ability to walk. The two remaining patients had a late-onset phenotype unreported to date. All patients (n = 29) had stable cerebellar atrophy. Our findings are in line with those of previous adult PMM2-CDG cohorts and points to the need for a multidisciplinary approach to the follow up of PMM2-CDG patients to prevent late complications. Additionally, our findings add weight to the view that PMM2-CDG may be diagnosed in teenage/adult patients with cerebellar atrophy, even in the absence of intellectual deficiency or non-neurological involvement.

  16. Elevated serum antiphospholipid antibodies in adults with celiac disease.

    Science.gov (United States)

    Laine, Outi; Pitkänen, Katariina; Lindfors, Katri; Huhtala, Heini; Niemelä, Onni; Collin, Pekka; Kurppa, Kalle; Kaukinen, Katri

    2018-05-01

    An increased incidence of thrombosis is suggested in celiac disease. We explored serum levels of antiphospholipid antibodies in untreated and treated adult celiac disease patients. A cohort of 179 biopsy-proven celiac disease patients (89 untreated, 90 on long-term gluten-free diet) and 91 non-celiac controls underwent clinical examination, assessment of celiac serology and enzyme immunoassay testing for anticardiolipin IgG and IgM, prothrombin IgG, and phosphatidylserine-prothrombin IgG and IgM. The level of antiphospholipid antibodies was higher in celiac disease patients compared with controls: anticardiolipin IgG 4.9 (0.7-33.8) vs 2.2 (0.4-9.6) U/ml, antiprothrombin IgG 2.9 (0.3-87.8) vs 2.1 (0.5-187.0) U/ml, antiphosphatidylserine-prothrombin IgG 6.9 (0.0-54.1) vs 2.3 (0.5-15.1) U/ml; p celiac disease at presentation (gastrointestinal symptoms, malabsorption or anemia, and extraintestinal symptoms or screen-detected disease) had no effect on the level of serum antiphospholipid antibodies. The serum level of antiphospholipid antibodies is increased in adults with celiac disease. The higher level of antibodies in treated patients suggests that the increase is not gluten-dependent. The prothrombotic role of antiphospholipid antibodies in celiac disease warrants further studies. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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.

  18. Progression from isolated growth hormone deficiency to combined pituitary hormone deficiency.

    Science.gov (United States)

    Cerbone, Manuela; Dattani, Mehul T

    2017-12-01

    Growth hormone deficiency (GHD) can present at any time of life from the neonatal period to adulthood, as a result of congenital or acquired insults. It can present as an isolated problem (IGHD) or in combination with other pituitary hormone deficiencies (CPHD). Pituitary deficits can evolve at any time from GHD diagnosis. The number, severity and timing of occurrence of additional endocrinopathies are highly variable. The risk of progression from IGHD to CPHD in children varies depending on the etiology (idiopathic vs organic). The highest risk is displayed by children with abnormalities in the Hypothalamo-Pituitary (H-P) region. Heterogeneous data have been reported on the type and timing of onset of additional pituitary hormone deficits, with TSH deficiency being most frequent and Diabetes Insipidus the least frequent additional deficit in the majority, but not all, of the studies. ACTH deficiency may gradually evolve at any time during follow-up in children or adults with childhood onset IGHD, particularly (but not only) in presence of H-P abnormalities and/or TSH deficiency. Hence there is a need in these patients for lifelong monitoring for ACTH deficiency. GH treatment unmasks central hypothyroidism mainly in patients with organic GHD, but all patients starting GH should have their thyroid function monitored closely. Main risk factors for development of CPHD include organic etiology, H-P abnormalities (in particular pituitary stalk abnormalities, empty sella and ectopic posterior pituitary), midline brain (corpus callosum) and optic nerves abnormalities, genetic defects and longer duration of follow-up. The current available evidence supports longstanding recommendations for the need, in all patients diagnosed with IGHD, of a careful and indefinite follow-up for additional pituitary hormone deficiencies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Modeling Late-Onset Sporadic Alzheimer’s Disease through BMI1 Deficiency

    Directory of Open Access Journals (Sweden)

    Anthony Flamier

    2018-05-01

    Full Text Available Late-onset sporadic Alzheimer’s disease (AD is the most prevalent form of dementia, but its origin remains poorly understood. The Bmi1/Ring1 protein complex maintains transcriptional repression of developmental genes through histone H2A mono-ubiquitination, and Bmi1 deficiency in mice results in growth retardation, progeria, and neurodegeneration. Here, we demonstrate that BMI1 is silenced in AD brains, but not in those with early-onset familial AD, frontotemporal dementia, or Lewy body dementia. BMI1 expression was also reduced in cortical neurons from AD patient-derived induced pluripotent stem cells but not in neurons overexpressing mutant APP and PSEN1. BMI1 knockout in human post-mitotic neurons resulted in amyloid beta peptide secretion and deposition, p-Tau accumulation, and neurodegeneration. Mechanistically, BMI1 was required to repress microtubule associated protein tau (MAPT transcription and prevent GSK3beta and p53 stabilization, which otherwise resulted in neurodegeneration. Restoration of BMI1 activity through genetic or pharmaceutical approaches could represent a therapeutic strategy against AD.

  20. Neuroendocrine and Cardiovascular Risk Factors in Adults with Pituitary Growth Hormone Deficiency (Literature Review

    Directory of Open Access Journals (Sweden)

    S.I. Ismailov

    2013-08-01

    Full Text Available In this article authors discussed the results of literature review, which has been dedicated to study of different complications of growth hormone deficiency in adults, referring to the literature of the last 10–15 years. Based on this analysis, the authors concluded that in adults with growth hormone deficiency there is an adverse profile of cardiovascular risk. Patients with growth hormone deficiency have an adverse lipid profile, elevated body mass index, increased waist circumference and a high risk of hypertension. These disorders are likely to explain the increased cardiovascular mortality observed in patients with hypopituitarism, regardless of the etiology of growth hormone deficiency in adults.

  1. Antithyroid Antibodies Are Implicated in Epileptogenesis of Adult Patients With Epilepsy

    OpenAIRE

    Tsai, Meng-Han; Fu, Ting-Ying; Chen, Nai-Ching; Shih, Fu-Yuan; Lu, Yan-Ting; Cheng, Mei-Yun; Chuang, Hung-Yi; Chuang, Yao-Chung

    2015-01-01

    Abstract Antithyroid antibodies (Abs) are associated with epilepsy in steroid-responsive encephalopathy, but have been rarely studied in unselected epilepsy patients. This study aimed to characterize the prevalence and associated factors of antithyroid Abs and other auto-Abs in adult patients with epilepsy. Epilepsy patients without autoimmune disorders were surveyed for antinuclear antibody (ANA), anti-?2 glycoprotein 1 antibody (a?2GP1), anticardiolipin IgG Ab, antimicrosomal antibody (AMA)...

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

    Directory of Open Access Journals (Sweden)

    Kumar Nilay

    2012-05-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusion Despite reported

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  5. Endocrinopathies in paediatric-onset neuromyelitis optica spectrum disorder with aquaporin 4 (AQP4) antibody.

    Science.gov (United States)

    Hacohen, Yael; Messina, Silvia; Gan, Hoong-Wei; Wright, Sukhvir; Chandratre, Saleel; Leite, Maria Isabel; Fallon, Penny; Vincent, Angela; Ciccarelli, Olga; Wassmer, Evangeline; Lim, Ming; Palace, Jacqueline; Hemingway, Cheryl

    2018-04-01

    The involvement of the diencephalic regions in neuromyelitis optica spectrum disorder (NMOSD) may lead to endocrinopathies. In this study, we identified the following endocrinopathies in 60% (15/25) of young people with paediatric-onset aquaporin 4-Antibody (AQP4-Ab) NMOSD: morbid obesity ( n = 8), hyperinsulinaemia ( n = 5), hyperandrogenism ( n = 5), amenorrhoea ( n = 5), hyponatraemia ( n = 4), short stature ( n = 3) and central hypothyroidism ( n = 2) irrespective of hypothalamic lesions. Morbid obesity was seen in 88% (7/8) of children of Caribbean origin. As endocrinopathies were prevalent in the majority of paediatric-onset AQP4-Ab NMOSD, endocrine surveillance and in particular early aggressive weight management is required for patients with AQP4-Ab NMOSD.

  6. Glucose 6 phosphate dehydrogenase deficiency in adults

    International Nuclear Information System (INIS)

    Khan, M.

    2004-01-01

    Objective: To determine the frequency of glucose-6-phosphate dehydrogenase (G6PD) deficiency in adults presented with anemia. Subjects and Methods: Eighteen months admission data was reviewed for G6PD deficiency as a cause of anemia. Anemia was defined by world health organization (WHO) criteria as haemoglobin less than 11.3 gm%. G6PD activity was measured by Sigma dye decolorisation method. All patients were screened for complications of hemolysis and its possible cause. Patients with more than 13 years of age were included in the study. Results: Out of 3600 patients admitted, 1440 were found anaemic and 49 as G6PD deficient. So the frequency of G6PD deficiency in anaemic patients was 3.4% and the overall frequency is 1.36%. G6PD deficiency among males and females was three and six percent respectively. Antimalarials and antibiotics containing sulphonamide group were the most common precipitating factors for hemolysis. Anemia and jaundice were the most common presentations while malaria was the most common associated disease. Acute renal failure was the most severe complication occurring in five patients with two deaths. Conclusion: G6PD deficiency is a fairly common cause of anemia with medicine as common precipitating factor for hemolysis. Such complications can be avoided with early recognition of the disease and avoiding indiscriminate use of medicine. (author)

  7. Seroprevalence of antibodies against chikungunya virus in Singapore resident adult population.

    Science.gov (United States)

    Ang, Li Wei; Kam, Yiu Wing; Lin, Cui; Krishnan, Prabha Unny; Tay, Joanne; Ng, Lee Ching; James, Lyn; Lee, Vernon J M; Goh, Kee Tai; Ng, Lisa F P; Lin, Raymond T P

    2017-12-01

    We determined the seroprevalence of chikungunya virus (CHIKV) infection in the adult resident population in Singapore following local outbreaks of chikungunya fever (CHIKF) in 2008-2009. Our cross-sectional study involved residual sera from 3,293 adults aged 18-79 years who had participated in the National Health Survey in 2010. Sera were tested for IgG antibodies against CHIKV and dengue virus (DENV) and neutralizing antibodies against CHIKV. The prevalence of CHIKV-neutralizing antibodies among Singapore residents aged 18-79 years was 1.9% (95% confidence interval: 1.4%- 2.3%). The CHIKV seroprevalence was highest in the elderly aged 70-79 years at 11.5%, followed by those aged 30-39 years at 3.1%. Men had significantly higher CHIKV seroprevalence than women (2.5% versus 1.3%, p = 0.01). Among the three main ethnic groups, Indians had the highest seroprevalence (3.5%) compared to Chinese (1.6%) and Malays (0.7%) (p = 0.02 and p = 0.01, respectively). Multivariable logistic regression identified adults aged 30-39 years and 70-79 years, men, those of Indian ethnicity and ethnic minority groups, and residence on ground floor of public and private housing apartments as factors that were significantly associated with a higher likelihood of exposure to CHIKV. The overall prevalence of anti-DENV IgG antibodies was 56.8% (95% CI: 55.1%- 58.5%), while 1.5% (95% CI: 1.1%- 2.0%) of adults possessed both neutralizing antibodies against CHIKV and IgG antibodies against DENV. Singapore remains highly susceptible to CHIKV infection. There is a need to maintain a high degree of vigilance through disease surveillance and vector control. Findings from such serological study, when conducted on a regular periodic basis, could supplement surveillance to provide insights on CHIKV circulation in at-risk population.

  8. Onset and organ specificity of Tk2 deficiency depends on Tk1 down-regulation and transcriptional compensation

    OpenAIRE

    Dorado, Beatriz; Area, Estela; Akman, Hasan O.; Hirano, Michio

    2010-01-01

    Deficiency of thymidine kinase 2 (TK2) is a frequent cause of isolated myopathy or encephalomyopathy in children with mitochondrial DNA (mtDNA) depletion. To determine the bases of disease onset, organ specificity and severity of TK2 deficiency, we have carefully characterized Tk2 H126N knockin mice (Tk2−/−). Although normal until postnatal day 8, Tk2−/− mice rapidly develop fatal encephalomyopathy between postnatal days 10 and 13. We have observed that wild-type Tk2 activity is constant in t...

  9. Perceived stress and risk of adult-onset asthma and other atopic disorders

    DEFF Research Database (Denmark)

    Rod, N H; Kristensen, T S; Lange, Peter

    2012-01-01

    BACKGROUND: Psychological stress can affect airway inflammatory response to irritants and allergens, but the importance of stress in the etiology of adult-onset respiratory and dermatologic allergic disorders remains unclear. We aim to address the relationship between perceived stress and the risk...... of adult-onset asthma, allergic rhinitis, atopic dermatitis, and asthma/bronchitis medication. METHODS: Participants (n = 9785) from the Copenhagen City Heart Study, Denmark, free of atopic disorders at baseline in 1981-1983 were asked questions on stress intensity and frequency. They were followed...

  10. Strategies for Successful Long-Term Engagement of Adults With Phenylalanine Hydroxylase Deficiency Returning to the Clinic

    Directory of Open Access Journals (Sweden)

    Janet Thomas MD

    2017-09-01

    Full Text Available Nearly half of all patients diagnosed with phenylalanine hydroxylase (PAH deficiency, also known as phenylketonuria, are lost to follow-up (LTFU; most are adults who stopped attending clinic after the age of 18 years. To understand why adult patients with PAH deficiency disengage from their clinic, a focus group of 8 adults with PAH deficiency who had been LTFU for 2 or more years was held in March 2016. Ten clinicians observed the focus group and discussed strategies for successfully reengaging adult patients and encouraging lifelong management of PAH deficiency. Four strategies were proposed: (1 create a safe, supportive environment, (2 acknowledge patients as partners in their care, (3 develop individualized management plans, and (4 provide patients with additional resources. These strategies provide a framework to motivate change in clinical practice to meet the unique needs of adults with PAH deficiency.

  11. Psychiatric adult-onset of urea cycle disorders: A case-series

    Directory of Open Access Journals (Sweden)

    Adrien Bigot

    2017-09-01

    Full Text Available Adult onset urea cycle disorders (UCD may present with psychiatric symptoms, occasionally as the initial presentation. We aimed to describe the characteristics of patients presenting with a psychiatric adult-onset of UCDs, to discuss which signs could suggest this diagnosis in such a situation, and to determine which tests should be conducted. A survey of psychiatric symptoms occurring in teenagers or adults with UCD was conducted in 2010 among clinicians involved in the French society for the study of inborn errors of metabolism (SFEIM. Fourteen patients from 14 to 57 years old were reported. Agitation was reported in 10 cases, perseveration in 5, delirium in 4, and disinhibition in 3 cases. Three patients had pre-existing psychiatric symptoms. All patients had neurological symptoms associated with psychiatric symptoms, such as ataxia or dysmetria, psychomotor slowing, seizures, or hallucinations. Fluctuations of consciousness and coma were reported in 9 cases. Digestive symptoms were reported in 7 cases. 9 patients had a personal history suggestive of UCD. The differential diagnoses most frequently considered were exogenous intoxication, non-convulsive status epilepticus, and meningoencephalitis. Hyperammonemia (180–600 μmol/L was found in all patients. The outcome was severe: mechanical ventilation was required in 10 patients, 5 patients died, and only 4 patients survived without sequelae. Adult onset UCDs can present with predominant psychiatric symptoms, associated with neurological involvement. These patients, as well as patients presenting with a suspicion of intoxication, must have UCD considered and ammonia measured without delay.

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

    Directory of Open Access Journals (Sweden)

    Catherine M. McMahon

    2013-01-01

    Full Text Available 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.

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

    Science.gov (United States)

    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 (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.

  14. Autoimmune Polyendocrine Syndrome 3 Onset with Severe Ketoacidosis in a 74-Year-Old Woman

    Directory of Open Access Journals (Sweden)

    Stefano Benedini

    2015-01-01

    Full Text Available Type 1 diabetes mellitus (T1D, autoimmune thyroid disease, and autoimmune gastritis often occur together forming the so-called autoimmune polyendocrine syndrome type 3 (APS3. We here report a clinical case of a 74-year-old woman who presented for the first time with severe hyperglycemia and ketoacidosis diagnosed as T1D. Further clinical investigations revealed concomitant severe hypothyroidism with autoimmune thyroid disease and severe cobalamin deficiency due to chronic atrophic gastritis. The diagnosis of type 1 diabetes mellitus was confirmed by the detection of autoantibodies against glutamic acid decarboxylase 65, islet cell antibodies, and anti-insulin autoantibodies. Anti-thyroperoxidase, anti-thyroglobulin, and anti-gastric parietal cell antibodies were also clearly positive. The case emphasized that new onset diabetic ketoacidosis, hypothyroidism, and cobalamin deficiency may simultaneously occur, and one disease can mask the features of the other, thereby making diagnosis difficult. It is noteworthy that an APS3 acute episode occurred in an asymptomatic elder woman for any autoimmune diseases.

  15. Inmunodeficiencias humorales: Un estudio en tres Centros de Inmunología Clínica de adultos en la Ciudad de Buenos Aires Antibody deficiencies: A survey from three Clinical Immunology Centers for adults in Buenos Aires City

    Directory of Open Access Journals (Sweden)

    Diego S. Fernández Romero

    2011-08-01

    infections of the respiratory tract. The aim of our study was to describe the clinical characteristics of 128 patients with suspected or confirmed AD who were referred to 3 immunodeficiency centers for adults, from June 2004 to December 2009. Three of these patients (2.3% consulted for recurrent infections only once, without sufficient data for a proper classification, and were excluded. Of the remaining 125 patients, in 21 (16.8% AD was excluded, 8 cases (6.4% were diagnosed with sec ondary antibody immunodeficiency (SAD and 96 (76.8% with primary antibody immunodeficiency (PAD. SAD causes were: one renal failure, one phenytoin use, two monoclonal gammopathy and four B cell lymphoma. The causes of these 96 PAD were: 57 common variable immunodeficiency, 12 X-linked agammaglobulinaemia, 10 selective IgA deficiency, seven IgG1 deficiency, three hyper- IgM syndrome, three IgM deficiency, two X-linked proliferative syndrome, one Good syndrome and one antibody functional deficiency. Sixty-seven patients were in follow up at the time of completion of the study, 25 of them were on follow up at the beginning of the study. Among the 58 patients with indication of gamma globulin replacement therapy, 54 were in treatment at the end of the study. In four patients the initial diagnosis of PAD was not confirmed.

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

    Science.gov (United States)

    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.

  17. A high seroprevalence of antibodies to pertussis toxin among Japanese adults: Qualitative and quantitative analyses.

    Directory of Open Access Journals (Sweden)

    Takumi Moriuchi

    Full Text Available In 2013, national serosurveillance detected a high seroprevalence of antibodies to pertussis toxin (PT from Bordetella pertussis among Japanese adults. Thus, we aimed to determine the cause(s of this high seroprevalence, and analyzed the titers of antibodies to PT and filamentous hemagglutinin (FHA among adults (35-44 years old, young children (4-7 years old, and older children (10-14 years old. Our quantitative analyses revealed that adults had higher seroprevalences of anti-PT IgG and PT-neutralizing antibodies, and similar titers of anti-FHA IgG, compared to the young and older children. Positive correlations were observed between the titers of PT-neutralizing antibodies and anti-PT IgG in all age groups (rs values of 0.326-0.522, although the correlation tended to decrease with age. The ratio of PT-neutralizing antibodies to anti-PT IgG was significantly different when we compared the serum and purified IgG fractions among adults (p = 0.016, although this result was not observed among young and older children. Thus, it appears that some adults had non-IgG immunoglobulins to PT. Our analyses also revealed that adults had high-avidity anti-PT IgG (avidity index: 63.5%, similar results were observed among the children; however, the adults had lower-avidity anti-FHA IgG (37.9%, p < 0.05. It is possible that low-avidity anti-FHA IgG is related to infection with other respiratory pathogens (e.g., Bordetella parapertussis, Haemophilus influenzae, or Mycoplasma pneumoniae, which produces antibodies to FHA-like proteins. Our observations suggest that these adults had been infected with B. pertussis and other pathogen(s during their adulthood.

  18. Adult-onset Still's disease: current challenges and future prospects

    Directory of Open Access Journals (Sweden)

    Siddiqui M

    2016-03-01

    Full Text Available Mariam Siddiqui,1 Michael S Putman,2 Anisha B Dua,11Department of Rheumatology, 2Department of Internal Medicine, The University of Chicago Medical Center, Chicago, IL, USA Abstract: Adult-onset Still's disease (AOSD – a multi-systemic inflammatory condition characterized by high fevers, polyarthritis, an evanescent rash, and pharyngitis – has been a challenging condition to diagnose expediently and treat effectively. Questions remain regarding the underlying pathophysiology and etiology of AOSD. Pathognomonic diagnostic tests and reliable biomarkers remain undiscovered. Over the past decade, important progress has been made. Diagnostic criteria employing glycosylated ferritin have improved specificity. More important, novel biologic therapies have offered important clues to AOSD's underlying pathophysiology. Cytokine-specific biologic therapies have been instrumental in providing more effective treatment for disease refractory to conventional treatment. While IL-1 therapy has demonstrated efficacy in refractory disease, novel therapies targeting IL-6 and IL-18 show great promise and are currently under investigation. Keywords: adult-onset Still's disease, biomarkers, therapeutics

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

    Science.gov (United States)

    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 DSM-5 criteria for diagnosing adult ADHD are not too lax regarding neuropsychological functioning.

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

    Science.gov (United States)

    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.

  1. Temporal discrimination threshold: VBM evidence for an endophenotype in adult onset primary torsion dystonia.

    LENUS (Irish Health Repository)

    Bradley, D

    2012-02-01

    Familial adult-onset primary torsion dystonia is an autosomal dominant disorder with markedly reduced penetrance. Most adult-onset primary torsion dystonia patients are sporadic cases. Disordered sensory processing is found in adult-onset primary torsion dystonia patients; if also present in their unaffected relatives this abnormality may indicate non-manifesting gene carriage. Temporal discrimination thresholds (TDTs) are abnormal in adult-onset primary torsion dystonia, but their utility as a possible endophenotype has not been examined. We examined 35 adult-onset primary torsion dystonia patients (17 familial, 18 sporadic), 42 unaffected first-degree relatives of both familial and sporadic adult-onset primary torsion dystonia patients, 32 unaffected second-degree relatives of familial adult-onset primary torsion dystonia (AOPTD) patients and 43 control subjects. TDT was measured using visual and tactile stimuli. In 33 unaffected relatives, voxel-based morphometry was used to compare putaminal volumes between relatives with abnormal and normal TDTs. The mean TDT in 26 control subjects under 50 years of age was 22.85 ms (SD 8.00; 95% CI: 19.62-26.09 ms). The mean TDT in 17 control subjects over 50 years was 30.87 ms (SD 5.48; 95% CI: 28.05-33.69 ms). The upper limit of normal, defined as control mean + 2.5 SD, was 42.86 ms in the under 50 years group and 44.58 ms in the over 50 years group. Thirty out of thirty-five (86%) AOPTD patients had abnormal TDTs with similar frequencies of abnormalities in sporadic and familial patients. Twenty-two out of forty-two (52%) unaffected first-degree relatives had abnormal TDTs with similar frequencies in relatives of sporadic and familial AOPTD patients. Abnormal TDTs were found in 16\\/32 (50%) of second-degree relatives. Voxel-based morphometry analysis comparing 13 unaffected relatives with abnormal TDTs and 20 with normal TDTs demonstrated a bilateral increase in putaminal grey matter in unaffected relatives with abnormal

  2. Clinical significance of enzymatic deficiencies in the gastrointestinal tract with particular reference to lactase deficiency.

    Science.gov (United States)

    Rossi, E; Lentze, M J

    1984-12-01

    The study of deficiencies of small intestinal brush-border hydrolases increased our knowledge about the specific functions of hydrolases in the digestion of smaller molecules on the microvillus surface of the absorptive cells. The sucrase-isomaltase (SI) complex has been shown to be synthesized as a precursor (pro-sucrase-isomaltase) which is then incorporated into the membrane. The hydrophobic N-terminal end of the molecule is anchored in the lipid bilayer. In SI deficiency the molecular base of the disease is still not clear. Absence of SI activity could be due to complete lack of precursor synthesis or to structural changes within the N-terminal end of the SI-complex. Deficiencies of peptide hydrolases have not been reported with the exception of enteropeptidase (EP). Here a congenital deficiency of the enzyme was observed as the primary defect in enzyme synthesis within the enterocytes and as a secondary defect due to exocrine pancreatic insufficiency. In contrast to the primary EP deficiency, the activity of EP can be restored in the cases of exocrine pancreatic insufficiency by treatment with pancreatic extracts. Primary lactase deficiency exists in various forms. Besides congenital lactase deficiency, the late onset or adult type of lactase deficiency has been observed. The latter occurs in many different ethnic groups around the world. Here, using gel electrophoresis and immunoelectrophoresis, the lack of enzyme activity could be shown to be a primary defect in enzyme protein synthesis. In man and in the rat, two different lactases have been identified. In contrast to adult lactase, fetal lactase contains sialic acid at the end of carbohydrate side chains.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. The evidence-based approach to adult-onset idiopathic nephrotic syndrome

    Directory of Open Access Journals (Sweden)

    Pietro A. Canetta

    2015-09-01

    Full Text Available Adult-onset nephrotic syndrome differs from its pediatric counterpart in several important ways. Most importantly, nephrotic syndrome in adults is more etiologically heterogeneous compared to children, and thus treatment approaches rely heavily on the histologic diagnosis provided by renal biopsy. The evidence-based approach to treatment of adult nephrotic syndrome 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.

  4. Protection by meningococcal outer membrane protein PorA-specific antibodies and a serogroup B capsular polysaccharide-specific antibody in complement-sufficient and C6-deficient infant rats.

    Science.gov (United States)

    Toropainen, Maija; Saarinen, Leena; Vidarsson, Gestur; Käyhty, Helena

    2006-05-01

    The relative contributions of antibody-induced complement-mediated bacterial lysis and antibody/complement-mediated phagocytosis to host immunity against meningococcal infections are currently unclear. Further, the in vivo effector functions of antibodies may vary depending on their specificity and Fc heavy-chain isotype. In this study, a mouse immunoglobulin G2a (mIgG2a) monoclonal antibody (MN12H2) to meningococcal outer membrane protein PorA (P1.16), its human IgG subclass derivatives (hIgG1 to hIgG4), and an mIgG2a monoclonal antibody (Nmb735) to serogroup B capsular polysaccharide (B-PS) were evaluated for passive protection against meningococcal serogroup B strain 44/76-SL (B:15:P1.7,16) in an infant rat infection model. Complement component C6-deficient (PVG/c-) rats were used to assess the importance of complement-mediated bacterial lysis for protection. The PorA-specific parental mIgG2a and the hIgG1 to hIgG3 derivatives all induced efficient bactericidal activity in vitro in the presence of human or infant rat complement and augmented bacterial clearance in complement-sufficient HsdBrlHan:WIST rats, while the hIgG4 was unable to do so. In C6-deficient PVG/c- rats, lacking complement-mediated bacterial lysis, the augmentation of bacterial clearance by PorA-specific mIgG2a and hIgG1 antibodies was impaired compared to that in the syngeneic complement-sufficient PVG/c+ rat strain. This was in contrast to the case for B-PS-specific mIgG2a, which conferred similar protective activity in both rat strains. These data suggest that while anti-B-PS antibody can provide protection in the infant rats without membrane attack complex formation, the protection afforded by anti-PorA antibody is more dependent on the activation of the whole complement pathway and subsequent bacterial lysis.

  5. Coexistence of adult-onset actinic prurigo and shampoo dermatitis: A case report

    Directory of Open Access Journals (Sweden)

    Tsung-Ju Lee

    2018-06-01

    Full Text Available Actinic prurigo is a rare and acquired idiopathic photodermatosis. It usually shows childhood onset and female predominance. Here, we present an unusual case of a male patient with coexistence of adult-onset actinic prurigo and shampoo-induced allergic contact dermatitis. He was initially diagnosed with actinic prurigo. However, after detailed examination of the distribution of the rash, careful collection of his history, and interpretation of the results of histopathologic analysis, photo test, patch test, and photopatch test, coexistence of adult-onset actinic prurigo and shampoo-induced allergic contact dermatitis associated with cocamidopropyl betaine was diagnosed. The rash improved after appropriate use of sunscreen and avoidance of shampoo containing this allergen. Dermatologists should be aware of the possibility of concurrent photodermatitis and contact dermatitis. Keywords: Actinic prurigo, Cocamidopropyl betaine, Contact dermatitis, Photosensitivity, Shampoo dermatitis

  6. Circulating CXCR5+PD-1+ response predicts influenza vaccine antibody responses in young adults but not elderly adults

    OpenAIRE

    Herati, Ramin Sedaghat; Reuter, Morgan A.; Dolfi, Douglas V.; Mansfield, Kathleen D.; Aung, Htin; Badwan, Osama Z.; Kurupati, Raj K.; Kannan, Senthil; Ertl, Hildegund; Schmader, Kenneth E.; Betts, Michael R.; Canaday, David H.; Wherry, E. John

    2014-01-01

    Although influenza vaccination is recommended for all adults annually, the incidence of vaccine failure, defined as weak or absent increase in neutralizing antibody titers, is increased in the elderly compared to young adults. The T follicular helper subset of CD4 T cells (Tfh) provides B cell help in germinal centers and is necessary for class-switched antibody responses. Previous studies suggested a role for circulating T follicular helper cells (cTfh) following influenza vaccination in adu...

  7. Post-operative Adult Onset Tic Disorder: A Rare Presentation.

    Science.gov (United States)

    Upadhyaya, Suneet Kumar; Raval, Chintan M; Sharma, Devendra Kumar; Vijayvergiya, Devendra Kumar

    2014-10-01

    Tics are rapid and repetitive muscle contractions resulting in stereotype movements and vocalizations that are experienced as involuntary. Onset before 18-year is a diagnostic criterion for tic disorders. Children and adolescents may exhibit tic behaviors after a stimulus or in response to an internal urge. Tic behaviors increase during physical or an emotional stress. Adult onset tic disorders are reported by infections, drugs, cocaine, toxins, chromosomal disorders, head injury, stroke, neurocutaneous syndromes, neurodegenerative disorders and peripheral injuries. Only few cases have yet been reported having onset after surgery though surgery brings both physical and emotional stress to the patient. We report a case of a 55-year-old lady who developed tic disorder as post-operative event of cataract surgery. Our patient had a dramatic response to haloperidol which is in contrast to all earlier reports.

  8. Adult-onset hypothyroidism enhances fear memory and upregulates mineralocorticoid and glucocorticoid receptors in the amygdala.

    Science.gov (United States)

    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.

  9. Adult-onset hypothyroidism enhances fear memory and upregulates mineralocorticoid and glucocorticoid receptors in the amygdala.

    Directory of Open Access Journals (Sweden)

    Ana Montero-Pedrazuela

    Full Text Available 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.

  10. Adult-Onset Hypothyroidism Enhances Fear Memory and Upregulates Mineralocorticoid and Glucocorticoid Receptors in the Amygdala

    Science.gov (United States)

    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

  11. Mortality and GH deficiency

    DEFF Research Database (Denmark)

    Stochholm, Kirstine; Gravholt, Claus Højbjerg; Laursen, Torben

    2007-01-01

    into childhood onset (CO) and adult onset (AO), discriminated by an age cutoff below or above 18 years at onset of GHD. METHOD: Data on death were identified in national registries. Sex- and cause-specific mortalities were identified in CO and AO GHD when compared with controls. RESULTS: Mortality was increased......OBJECTIVE: To estimate the mortality in Denmark in patients suffering from GH deficiency (GHD). DESIGN: Mortality was analyzed in 1794 GHD patients and 8014 controls matched on age and gender. All records in GHD patients were studied and additional morbidity noted. Patients were divided...... in CO and AO GHD in both genders, when compared with controls. The hazard ratio (HR) for CO males was 8.3 (95% confidence interval (CI) 4.5-15.1) and for females 9.4 (CI 4.6-19.4). For AO males, HR was 1.9 (CI 1.7-2.2) and for females 3.4 (CI 2.9-4.0). We found a significantly higher HR in AO females...

  12. Radiographic abnormalities of the wrist in adult-onset still disease: Comparison with juvenile chronic arthritis and rheumatoid arthritis

    International Nuclear Information System (INIS)

    Bjorkengren, A.G.; Pathria, M.N.; Terkeltaub, R.; Esdaile, J.; Weisman, M.; Sartoris, D.J.; Resnick, D.

    1987-01-01

    Pericapitate involvement of the wrist has been described as characteristic of adult-onset Still disease, a relatively rare disorder that is often diagnosed by exclusion after extensive and frequently invasive tests. To evaluate the diagnostic value of carpal radiography in cases of adult-onset Still disease, a retrospective blinded analysis of 48 patients, 16 each with adult-onset Still disease, juvenile chronic arthritis, and rheumatoid arthritis, was performed. Pericapitate articular alterations without radiocarpal involvement were found to be frequent in the setting of adult-onset Still disease but distinctly unusual among patients with rheumatoid arthritis. In juvenile chronic arthritis, severe pericapitate involvement was frequent, but generally occurred in conjunction with radiocarpal joint abnormalities

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

    Science.gov (United States)

    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

  14. Juvenile-onset loss of lipid-raft domains in attractin-deficient mice

    International Nuclear Information System (INIS)

    Azouz, Abdallah; Gunn, Teresa M.; Duke-Cohan, Jonathan S.

    2007-01-01

    Mutations at the attractin (Atrn) locus in mice result in altered pigmentation on an agouti background, higher basal metabolic rate and juvenile-onset hypomyelination leading to neurodegeneration, while studies on human immune cells indicate a chemotaxis regulatory function. The underlying biochemical defect remains elusive. In this report we identify a role for attractin in plasma membrane maintenance. In attractin's absence there is a decline in plasma membrane glycolipid-enriched rafts from normal levels at 8 weeks to a complete absence by 24 weeks. The structural integrity of lipid rafts depends upon cholesterol and sphingomyelin, and can be identified by partitioning within of ganglioside GM 1 . Despite a significant fall in cellular cholesterol with maturity, and a lesser fall in both membrane and total cellular GM 1 , these parameters lag behind raft loss, and are normal when hypomyelination/neurodegeneration has already begun thus supporting consequence rather than cause. These findings can be recapitulated in Atrn-deficient cell lines propagated in vitro. Further, signal transduction through complex membrane receptor assemblies is not grossly disturbed despite the complete absence of lipid rafts. We find these results compatible with a role for attractin in plasma membrane maintenance and consistent with the proposal that the juvenile-onset hypomyelination and neurodegeneration represent a defect in attractin-mediated raft-dependent myelin biogenesis

  15. Onset and organ specificity of Tk2 deficiency depends on Tk1 down-regulation and transcriptional compensation.

    Science.gov (United States)

    Dorado, Beatriz; Area, Estela; Akman, Hasan O; Hirano, Michio

    2011-01-01

    Deficiency of thymidine kinase 2 (TK2) is a frequent cause of isolated myopathy or encephalomyopathy in children with mitochondrial DNA (mtDNA) depletion. To determine the bases of disease onset, organ specificity and severity of TK2 deficiency, we have carefully characterized Tk2 H126N knockin mice (Tk2-/-). Although normal until postnatal day 8, Tk2-/- mice rapidly develop fatal encephalomyopathy between postnatal days 10 and 13. We have observed that wild-type Tk2 activity is constant in the second week of life, while Tk1 activity decreases significantly between postnatal days 8 and 13. The down-regulation of Tk1 activity unmasks Tk2 deficiency in Tk2-/- mice and correlates with the onset of mtDNA depletion in the brain and the heart. Resistance to pathology in Tk2 mutant organs depends on compensatory mechanisms to the reduced mtDNA level. Our analyses at postnatal day 13 have revealed that Tk2-/- heart significantly increases mitochondrial transcript levels relative to the mtDNA content. This transcriptional compensation allows the heart to maintain normal levels of mtDNA-encoded proteins. The up-regulation in mitochondrial transcripts is not due to increased expression of the master mitochondrial biogenesis regulators peroxisome proliferator-activated receptor-gamma coactivator 1 alpha and nuclear respiratory factors 1 and 2, or to enhanced expression of the mitochondrial transcription factors A, B1 or B2. Instead, Tk2-/- heart compensates for mtDNA depletion by down-regulating the expression of the mitochondrial transcriptional terminator transcription factor 3 (MTERF3). Understanding the molecular mechanisms that allow Tk2 mutant organs to be spared may help design therapies for Tk2 deficiency.

  16. Extensive expertise in endocrinology: UK stance on adult GH replacement: the economist vs the endocrinologist.

    Science.gov (United States)

    Shalet, S M

    2013-10-01

    In the UK, through the use of a forced economic model, endocrinologists are in the curious position of offering GH replacement to some patients with severe GH deficiency (GHD) but withholding it from other patients with even more severe GHD. This approach is counter-intuitive to endocrine practice in treating endocrine deficiency states. For all other endocrine deficiencies, one would opt for treating those with the most severe biochemical evidence of deficiency first. If this endocrine approach was applied to adult GH replacement in an era of rationing, one would start with the GHD patients with a pathologically low IGF1 level. Given that the prevalence of subnormal IGF1 levels in a GHD population is age-dependent, this would result in GH replacement being offered to more young adult onset (AO) GHD and childhood onset GHD adults, and less often to middle-aged and elderly AO GHD adults. This in itself has the added advantage that the skeletal benefits appear more real in the former cohort of patients.

  17. Thyroid peroxidase antibodies during early gestation and the subsequent risk of first-onset postpartum depression: A prospective cohort study

    NARCIS (Netherlands)

    R. Wesseloo (Richard); A.M. Kamperman (Astrid); V. Bergink (Veerle); V.J.M. Pop (Victor)

    2017-01-01

    markdownabstract__Background__ During the postpartum period, women are at risk for the new onset of both auto-immune thyroid disorders and depression. The presence of thyroid peroxidase antibodies (TPO-ab) during early gestation is predictive for postpartum auto-immune thyroid dysfunction. The aim

  18. Na(v)1.8 channelopathy in mutant mice deficient for myelin protein zero is detrimental to motor axons

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Alvarez Herrero, Susana; Pinchenko, Volodymyr

    2011-01-01

    Myelin protein zero mutations were found to produce Charcot-Marie-Tooth disease phenotypes with various degrees of myelin impairment and axonal loss, ranging from the mild 'demyelinating' adult form to severe and early onset forms. Protein zero deficient homozygous mice ( ) show a severe and prog......Myelin protein zero mutations were found to produce Charcot-Marie-Tooth disease phenotypes with various degrees of myelin impairment and axonal loss, ranging from the mild 'demyelinating' adult form to severe and early onset forms. Protein zero deficient homozygous mice ( ) show a severe...... and progressive dysmyelinating neuropathy from birth with compromised myelin compaction, hypomyelination and distal axonal degeneration. A previous study using immunofluorescence showed that motor nerves deficient of myelin protein zero upregulate the Na(V)1.8 voltage gated sodium channel isoform, which...... is normally present only in restricted populations of sensory axons. The aim of this study was to investigate the function of motor axons in protein zero-deficient mice with particular emphasis on ectopic Na(V)1.8 voltage gated sodium channel. We combined 'threshold tracking' excitability studies...

  19. ADULT-ONSET STILL'S DISEASE: DIAGNOSIS AND TREATMENT

    Directory of Open Access Journals (Sweden)

    Rimma Mikhailovna Balabanova

    2009-09-01

    Full Text Available The paper describes adult-onset Still's disease (AOSD, a rare multisystemic disease of unknown etiology that is referred to as seronegative rheumatoid arthritis. It presents the major manifestations of AOSD: long-term fever, arthritis or persistent arthralgias, maculopapular eruption, seronegativity for rheumatoid factor, neutrophilic leukocytosis, and disease onset after 16 years of age, as well as additional signs: lymphadenopathy, hepatosplenomegaly, polyserositis, nasopharyngeal infection. It is noted that particular difficulties in the diagnosis of AOSD emerge when it is complicated by the hematophagocytic syndrome (HPS. The distinctive features of AOSD are the development of cutaneous and articular symptoms in practically 80% of patients and their absence in HPS. It is stated that of greater value in the diagnosis of HPS is examination of aspirate of the bone marrow than its biopsy. Most patients develop refractoriness to glucocorticoids and essential anti-inflammatory drugs. The positive results of using anakinra, rituximab, and tocilizumab are promising.

  20. ADULT-ONSET STILL'S DISEASE: DIAGNOSIS AND TREATMENT

    Directory of Open Access Journals (Sweden)

    Rimma Mikhailovna Balabanova

    2009-01-01

    Full Text Available The paper describes adult-onset Still's disease (AOSD, a rare multisystemic disease of unknown etiology that is referred to as seronegative rheumatoid arthritis. It presents the major manifestations of AOSD: long-term fever, arthritis or persistent arthralgias, maculopapular eruption, seronegativity for rheumatoid factor, neutrophilic leukocytosis, and disease onset after 16 years of age, as well as additional signs: lymphadenopathy, hepatosplenomegaly, polyserositis, nasopharyngeal infection. It is noted that particular difficulties in the diagnosis of AOSD emerge when it is complicated by the hematophagocytic syndrome (HPS. The distinctive features of AOSD are the development of cutaneous and articular symptoms in practically 80% of patients and their absence in HPS. It is stated that of greater value in the diagnosis of HPS is examination of aspirate of the bone marrow than its biopsy. Most patients develop refractoriness to glucocorticoids and essential anti-inflammatory drugs. The positive results of using anakinra, rituximab, and tocilizumab are promising.

  1. Clinical Manifestations and Treatment of Adult-Onset Asthma and Periocular Xanthogranuloma

    Directory of Open Access Journals (Sweden)

    Rodrigo Cavallazzi

    2009-01-01

    Full Text Available BACKGROUND: Adult-onset asthma and periocular xanthogranuloma is an uncommon and recently described disease. Little is known about the condition because only a few case reports and series are available.

  2. Laryngeal Neuropathy in Adult Goats With Copper Deficiency.

    Science.gov (United States)

    Sousa, R F A; Almeida, V M; Neto, J E; Nascimento, C W A; Medeiros, G X; Medeiros, R M T; Riet-Correa, F; Mendonça, F S

    2017-07-01

    The aim of this study was to elucidate the cause of a neurological syndrome characterized by stridor in adult goats with clinical signs of copper deficiency. The main clinical signs consisted of apathy, emaciation, pale mucous membranes, mucous nasal discharge, dyspnea, severe achromotrichia, diffuse alopecia, torpor, ataxia, and stridor. When the goats were forced to move, the stridor increased. In a herd of 194 Toggenburg goats, 10 adult goats with clinical signs of copper deficiency were removed from the herd and divided into 2 groups: group 1, which consisted of 4 nannies and 1 buck with stridor, and group 2, which consisted of 4 nannies and 1 buck without stridor. Group 3, used as a control, consisted of 5 adult goats from another flock without any clinical signs of disease. The mean serum copper concentrations were 1.3 ± 0.3 μmol/L in group 1, 8.1 ± 1.1 μmol/L in group 2, and 11.3 ± 2.2 μmol/L in group 3. The mean serum iron concentrations were 42.3 ± 14.2 μmol/L in group 1, 39.1 ± 8.2 μmol/L in group 2, and 20.6 ± 6.1 μmol/L in group 3. The main histological lesions in goats from group 1 were axonal degeneration of the recurrent laryngeal nerves and atrophy of the muscles of vocal folds and of the dorsal cricoarytenoid and right and left cricothyroid muscles. Goats with ataxia had neuronal degeneration and necrosis of cerebellar Purkinje cells and of the cranial cervical ganglion. We concluded that the stridor was caused by axonal degeneration of the recurrent laryngeal nerves due to the severe copper deficiency.

  3. New function for an old enzyme: NEP deficient mice develop late-onset obesity.

    Directory of Open Access Journals (Sweden)

    Matthias Becker

    Full Text Available BACKGROUND: According to the World Health Organization (WHO there is a pandemic of obesity with approximately 300 million people being obese. Typically, human obesity has a polygenetic causation. Neutral endopeptidase (NEP, also known as neprilysin, is considered to be one of the key enzymes in the metabolism of many active peptide hormones. METHODOLOGY/PRINCIPAL FINDINGS: An incidental observation in NEP-deficient mice was a late-onset excessive gain in body weight exclusively from a ubiquitous accumulation of fat tissue. In accord with polygenetic human obesity, mice were characterized by deregulation of lipid metabolism, higher blood glucose levels, with impaired glucose tolerance. The key role of NEP in determining body mass was confirmed by the use of the NEP inhibitor candoxatril in wild-type mice that increased body weight due to increased food intake. This is a peripheral and not a central NEP action on the switch for appetite control, since candoxatril cannot cross the blood-brain barrier. Furthermore, we demonstrated that inhibition of NEP in mice with cachexia delayed rapid body weight loss. Thus, lack in NEP activity, genetically or pharmacologically, leads to a gain in body fat. CONCLUSIONS/SIGNIFICANCE: In the present study, we have identified NEP to be a crucial player in the development of obesity. NEP-deficient mice start to become obese under a normocaloric diet in an age of 6-7 months and thus are an ideal model for the typical human late-onset obesity. Therefore, the described obesity model is an ideal tool for research on development, molecular mechanisms, diagnosis, and therapy of the pandemic obesity.

  4. Thyroid peroxidase antibodies during early gestation and the subsequent risk of first onset postpartum depression : A prospective cohort study

    NARCIS (Netherlands)

    Wesseloo, R.; Kamperman, A.; Bergink, V.; Pop, V.J.M.

    2018-01-01

    Background During the postpartum period, women are at risk for the new onset of both auto-immune thyroid disorders and depression. The presence of thyroid peroxidase antibodies (TPO-ab) during early gestation is predictive for postpartum auto-immune thyroid dysfunction. The aim of this study was to

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

    Science.gov (United States)

    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.

  6. Vitamin D Deficiency and Cardiometabolic Risks: A Juxtaposition of Arab Adolescents and Adults.

    Directory of Open Access Journals (Sweden)

    Nasser M Al-Daghri

    Full Text Available The recent exponential surge in vitamin D research reflects the global epidemic of vitamin D deficiency and its potential impact on several chronic diseases in both children and adults. Several subpopulations, including Arab adolescent boys and girls, remain understudied. This study aims to fill this gap. A total of 2225 apparently healthy Saudi adolescents (1187 boys and 1038 girls, aged 13-17 years old and 830 adults (368 men and 462 women, aged 18-50 years old were respectively recruited from different public schools and medical practices within Riyadh, Saudi Arabia. Anthropometrics were taken and fasting blood samples withdrawn to examine serum glucose and lipid profile by routine analysis and 25-hydroxyvitamin D by ELISA. Almost half of the girls (47.0% had vitamin D deficiency as compared to only 19.4% of the boys (p<0.001, 36.8% of the adult women and 17.7% of the adult men (p<0.001. Furthermore, in boys there were more significant inverse associations between serum 25(OHvitamin D levels and cardiometabolic indices than girls, while in contrast women had more significant associations than men. Vitamin D deficiency was significantly associated with diabetes mellitus type 2 (DMT2 [OR 3.47 (CI1.26-5.55; p<0.05] and pre-DM [OR 2.47 (CI 1.48-4.12; p<0.01] in boys. Furthermore, vitamin D insufficiency was significantly associated with abdominal obesity in boys [OR 2.75 (CI 1.1-7.1; p<0.05]. These associations for DMT2 and abdominal obesity were not observed in adult males, girls and adult women. Vitamin D deficiency/insufficiency and hyperglycemia is high among Arab adolescents. Vitamin D deficiency is mostly associated with cardiometabolic risk factors in adolescent Arab boys. This indicates a sex- and age-related disadvantage for boys with low vitamin D status and challenges the extra-skeletal protection of vitamin D correction in adolescent females.

  7. Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency

    DEFF Research Database (Denmark)

    Andresen, B S; Olpin, S; Poorthuis, B J

    1999-01-01

    Very-long-chain acyl-CoA dehydrogenase (VLCAD) catalyzes the initial rate-limiting step in mitochondrial fatty acid beta-oxidation. VLCAD deficiency is clinically heterogenous, with three major phenotypes: a severe childhood form, with early onset, high mortality, and high incidence of cardiomyop......Very-long-chain acyl-CoA dehydrogenase (VLCAD) catalyzes the initial rate-limiting step in mitochondrial fatty acid beta-oxidation. VLCAD deficiency is clinically heterogenous, with three major phenotypes: a severe childhood form, with early onset, high mortality, and high incidence...... of cardiomyopathy; a milder childhood form, with later onset, usually with hypoketotic hypoglycemia as the main presenting feature, low mortality, and rare cardiomyopathy; and an adult form, with isolated skeletal muscle involvement, rhabdomyolysis, and myoglobinuria, usually triggered by exercise or fasting......-phenotype relationship is in sharp contrast to what has been observed in medium-chain acyl-CoA dehydrogenase deficiency, in which no correlation between genotype and phenotype can be established....

  8. Clinical value of NPHS2 analysis in early- and adult-onset steroid-resistant nephrotic syndrome.

    Science.gov (United States)

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

    2011-02-01

    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. 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. 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. 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.

  9. Prevalence and titers of yellow fever virus neutralizing antibodies in previously vaccinated adults.

    Science.gov (United States)

    Miyaji, Karina Takesaki; Avelino-Silva, Vivian Iida; Simões, Marisol; Freire, Marcos da Silva; Medeiros, Carlos Roberto de; Braga, Patrícia Emilia; Neves, Maria Angélica Acalá; Lopes, Marta Heloisa; Kallas, Esper Georges; Sartori, Ana Marli Christovam

    2017-04-03

    The World Health Organization (WHO) recommends one single dose of the Yellow Fever (YF) vaccine based on studies of antibody persistency in healthy adults. We assessed the prevalence and titers of YF virus neutralizing antibodies in previously vaccinated persons aged  60 years, in comparison to younger adults. We also evaluated the correlation between antibody titers and the time since vaccination among participants who received one vaccine dose, and the seropositivity among participants vaccinated prior to or within the past 10 years. previously vaccinated healthy persons aged  18 years were included. YF virus neutralizing antibody titers were determined by means of the 50% Plaque Reduction Neutralization Test. 46 persons aged  60 years and 48 persons aged 18 to 59 years were enrolled. There was no significant difference in the prevalence of YF virus neutralizing antibodies between the two groups (p = 0.263). However, titers were significantly lower in the elderly (p = 0.022). There was no correlation between YF virus neutralizing antibody titers and the time since vaccination. There was no significant difference in seropositivity among participants vaccinated prior to or within the past 10 years. the clinical relevance of the observed difference in YF virus neutralizing antibody titers between the two groups is not clear.

  10. Atypical presentation of late-onset Tay-Sachs disease.

    Science.gov (United States)

    Deik, Andres; Saunders-Pullman, Rachel

    2014-05-01

    Late-onset Tay-Sachs disease (LOTS) is a lysosomal storage disease caused by deficient Beta-hexosaminidase A activity. We describe a 53-year-old woman who presented with adult-onset leg weakness, and whose initial diagnosis was progressive muscular atrophy without identifiable etiology. Development of cerebellar ataxia in mid-life prompted reassessment. Beta-hexosaminidase A quantification assay demonstrated absence of the isozyme. Genetic testing identified compound heterozygous mutations in the HEXA gene, confirming the diagnosis of LOTS. The phenotypic spectrum of LOTS includes motor neuronopathy, ataxia, choreoathetosis, neuropathy, and psychiatric symptoms in various combinations. This patient highlights the emergence of different clinical features over many years and emphasizes the need to consider LOTS in the differential diagnosis of progressive muscular atrophy. Copyright © 2013 Wiley Periodicals, Inc.

  11. Investigating the Effectiveness, Acceptability and Impact on Healthcare Usage of Providing a Cognitive-Behavioural Based Psychological Therapy Service for Patients with Primary Antibody Deficiency.

    Science.gov (United States)

    Campbell, Mari; Clarke, Alex; Symes, Andrew; Workman, Sarita; Stauss, Hans; Webster, A David

    2018-02-01

    Patients with primary antibody deficiency report poorer quality of life and higher rates of anxiety and depression than the general population. Cognitive-behavioral therapy has been shown to be a valuable treatment for patients with other long-term physical health conditions, improving well-being and enabling them to manage their symptoms more effectively. The aim of this project was to establish the feasibility and effectiveness of providing cognitive-behavioral based therapy to patients with primary antibody deficiency. Forty-four patients completed a course of psychological therapy. Participants completed a series of self-report measures examining psychological and physical health, and service usage, prior to starting treatment and following their final session. They also provided feedback on their experience of treatment. Patients showed improvements in anxiety, depression, insomnia and fatigue. There was a high level of acceptability of the service and the potential for long-term cost savings to the NHS. Psychological therapy based on the cognitive-behavioral model of treatment appears to be a valuable treatment for patients with primary antibody deficiency and comorbid mental health difficulties.

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

    Science.gov (United States)

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

    2016-06-01

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

  13. GAD Antibody-Associated Late-Onset Cerebellar Ataxia in Two Female Siblings

    Directory of Open Access Journals (Sweden)

    Joseph Kuchling

    2014-11-01

    Full Text Available Background: Anti-glutamic acid decarboxylase antibody (GAD-ab-associated cerebellar ataxia is a rare neurological disorder characterized by cerebellar symptoms concomitant with high GAD-ab levels in serum and cerebrospinal fluid (CSF. Case Report: We report on 2 female siblings (aged 74 and 76 years presenting with gradual progression of rotational vertigo, gait ataxia and vertical diplopia, continuously progressing for 6 months and 6 years, respectively. Autoimmune laboratory examinations showed remarkably increased serum and CSF GAD-ab levels. Their medical histories revealed late-onset type 1 diabetes mellitus (T1DM and other concomitant autoimmune disorders (Grave's disease, Hashimoto's thyroiditis. Cerebral MRI and laboratory examinations were unremarkable. The diagnosis of GAD-ab-associated cerebellar ataxia with particular brainstem involvement was established in both women. After the exclusion of an underlying malignancy, immunosuppressive therapy has been initiated in both patients, which resulted in stabilization in one and in clinical improvement in the other patient. Discussion: The unique association of autoantibody-mediated cerebellar ataxia and late-onset T1DM in 2 siblings with similar clinical and paraclinical phenotypes strengthens the concept that hereditary factors might play a relevant role also in autoimmune diseases so far considered to be sporadic. Moreover, the occurrence of continuous vertical diplopia broadens the clinical spectrum of GAD-ab-associated neurological syndromes.

  14. Dioxin (TCDD induces epigenetic transgenerational inheritance of adult onset disease and sperm epimutations.

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    Mohan Manikkam

    Full Text Available 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.

  15. Maternal Antibody-Mediated Disease Enhancement in Type I Interferon-Deficient Mice Leads to Lethal Disease Associated with Liver Damage.

    Directory of Open Access Journals (Sweden)

    Julia María Martínez Gómez

    2016-03-01

    Full Text Available Epidemiological studies have reported that most of the severe dengue cases occur upon a secondary heterologous infection. Furthermore, babies born to dengue immune mothers are at greater risk of developing severe disease upon primary infection with a heterologous or homologous dengue virus (DENV serotype when maternal antibodies reach sub-neutralizing concentrations. These observations have been explained by the antibody mediated disease enhancement (ADE phenomenon whereby heterologous antibodies or sub-neutralizing homologous antibodies bind to but fail to neutralize DENV particles, allowing Fc-receptor mediated entry of the virus-antibody complexes into host cells. This eventually results in enhanced viral replication and heightened inflammatory responses. In an attempt to replicate this ADE phenomenon in a mouse model, we previously reported that upon DENV2 infection 5-week old type I and II interferon (IFN receptors-deficient mice (AG129 born to DENV1-immune mothers displayed enhancement of disease severity characterized by increased virus titers and extensive vascular leakage which eventually led to the animals' death. However, as dengue occurs in immune competent individuals, we sought to reproduce this mouse model in a less immunocompromised background. Here, we report an ADE model that is mediated by maternal antibodies in type I IFN receptor-deficient A129 mice. We show that 5-week old A129 mice born to DENV1-immune mothers succumbed to a DENV2 infection within 4 days that was sub-lethal in mice born to naïve mothers. Clinical manifestations included extensive hepatocyte vacuolation, moderate vascular leakage, lymphopenia, and thrombocytopenia. Anti-TNFα therapy totally protected the mice and correlated with healthy hepatocytes. In contrast, blocking IL-6 did not impact the virus titers or disease outcome. This A129 mouse model of ADE may help dissecting the mechanisms involved in dengue pathogenesis and evaluate the efficacy of

  16. Season of Birth and Risk for Adult Onset Glioma

    Directory of Open Access Journals (Sweden)

    Jimmy T. Efird

    2010-04-01

    Full Text Available Adult onset glioma is a rare cancer which occurs more frequently in Caucasians than African Americans, and in men than women. The etiology of this disease is largely unknown. Exposure to ionizing radiation is the only well established environmental risk factor, and this factor explains only a small percentage of cases. Several recent studies have reported an association between season of birth and glioma risk. This paper reviews the plausibility of evidence focusing on the seasonal interrelation of farming, allergies, viruses, vitamin D, diet, birth weight, and handedness. To date, a convincing explanation for the occurrence of adult gliomas decades after a seasonal exposure at birth remains elusive.

  17. Differentiation of adult-type Leydig cells occurs in gonadotrophin-deficient mice

    Directory of Open Access Journals (Sweden)

    Charlton HM

    2003-02-01

    Full Text Available Abstract During mammalian testis development distinct generations of fetal and adult Leydig cells arise. Luteinising hormone (LH is required for normal adult Leydig cell function and for the establishment of normal adult Leydig cell number but its role in the process of adult Leydig cell differentiation has remained uncertain. In this study we have examined adult Leydig cell differentiation in gonadotrophin-releasing hormone (GnRH-null mice which are deficient in circulating gonadotrophins. Adult Leydig cell differentiation was assessed by measuring expression of mRNA species encoding four specific markers of adult Leydig cell differentiation in the mouse. Each of these markers (3β-hydroxysteroid dehydrogenase type VI (3βHSD VI, 17β-hydroxysteroid dehydrogenase type III (17βHSD III, prostaglandin D (PGD-synthetase and oestrogen sulphotransferase (EST is expressed only in the adult Leydig cell lineage in the normal adult animal. Real-time PCR studies showed that all four markers are expressed in adult GnRH-null mice. Localisation of 3βHSD VI and PGD-synthetase expression by in situ hybridisation confirmed that these genes are expressed in the interstitial tissue of the GnRH-null mouse. Treatment of animals with human chorionic gonadotrophin increased expression of 3βHSD VI and 17βHSD III within 12 hours further indicating that differentiated, but unstimulated cells already exist in the GnRH-null mouse. Thus, while previous studies have shown that LH is required for adult Leydig cell proliferation and activity, results from the present study show that adult Leydig cell differentiation will take place in animals deficient in LH.

  18. Growth hormone deficiency in children and young adults.

    Science.gov (United States)

    Oświęcimska, Joanna; Roczniak, Wojciech; Mikołajczak, Agata; Szymlak, Agnieszka

    2016-09-13

    Growth hormone (GH) is a naturally occurring polypeptide hormone produced by somatotropic cells in the anterior pituitary. The main function of somatotropin is stimulation of linear growth, but it also affects carbohydrate metabolism, increases bone mass and has potent lipolytic, antinatriuretic and antidiuretic effects. Growth hormone deficiency (GHD) may occur both in children and in adults. At the moment there is no gold standard for the diagnosis of GHD, and the diagnosis should take into account clinical, auxological, biochemical and radiological changes and, if necessary, genetic testing. Recent studies have highlighted that the biochemical diagnosis of GH deficiency is still imperfect. Stimuli used in the tests are non-physiological, and various substances are characterized by a different mechanism of action and potency. A few years ago it was thought that GHD treatment in children must be completed at the end of linear growth. Studies performed in the last two decades have shown that GHD deficiency in adults may result in complex clinical problems, and if untreated shortens the life expectancy and worsens its comfort. Discontinuation of GH therapy after the final height has been reached in fact negatively impacts the physiological processes associated with the transition phase, which is the period of human life between achieving the final height and 25-30 years of age. Given the adverse metabolic effects of GH treatment interruption after linear growth has been completed, the latest recommendations propose reassessment of GH secretion in the period at least one month after cessation of treatment and continuation of the therapy in case of persistent deficit.

  19. Growth hormone deficiency in children and young adults

    Directory of Open Access Journals (Sweden)

    Joanna Oświęcimska

    2016-09-01

    Full Text Available Growth hormone (GH is a naturally occurring polypeptide hormone produced by somatotropic cells in the anterior pituitary. The main function of somatotropin is stimulation of linear growth, but it also affects carbohydrate metabolism, increases bone mass and has potent lipolytic, antinatriuretic and antidiuretic effects. Growth hormone deficiency (GHD may occur both in children and in adults. At the moment there is no gold standard for the diagnosis of GHD, and the diagnosis should take into account clinical, auxological, biochemical and radiological changes and, if necessary, genetic testing. Recent studies have highlighted that the biochemical diagnosis of GH deficiency is still imperfect. Stimuli used in the tests are non-physiological, and various substances are characterized by a different mechanism of action and potency. A few years ago it was thought that GHD treatment in children must be completed at the end of linear growth. Studies performed in the last two decades have shown that GHD deficiency in adults may result in complex clinical problems, and if untreated shortens the life expectancy and worsens its comfort. Discontinuation of GH therapy after the final height has been reached in fact negatively impacts the physiological processes associated with the transition phase, which is the period of human life between achieving the final height and 25-30 years of age. Given the adverse metabolic effects of GH treatment interruption after linear growth has been completed, the latest recommendations propose reassessment of GH secretion in the period at least one month after cessation of treatment and continuation of the therapy in case of persistent deficit.

  20. Epidemiology and pathophysiology of adulthood-onset thrombotic microangiopathy with severe ADAMTS13 deficiency (thrombotic thrombocytopenic purpura): a cross-sectional analysis of the French national registry for thrombotic microangiopathy.

    Science.gov (United States)

    Mariotte, Eric; Azoulay, Elie; Galicier, Lionel; Rondeau, Eric; Zouiti, Fouzia; Boisseau, Pierre; Poullin, Pascale; de Maistre, Emmanuel; Provôt, François; Delmas, Yahsou; Perez, Pierre; Benhamou, Ygal; Stepanian, Alain; Coppo, Paul; Veyradier, Agnès

    2016-05-01

    Thrombotic thrombocytopenic purpura is a thrombotic microangiopathy related to a severe deficiency of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13; activity purpura at initial presentation. Between Jan 1, 1999, and Dec 31, 2013, we did a cross-sectional analysis of the French national registry for thrombotic microangiopathy to identify all patients with adult-onset thrombotic microangiopathy (first episode after age 18 years) who had severe ADAMTS13 deficiency at presentation. ADAMTS13 activity, anti-ADAMTS13 IgG, and ADAMTS13 gene mutations were investigated by a central laboratory. We collected patients' clinical data for correlation with their ADAMTS13 phenotype and genotype. We used logistic regression analysis to identify variables significantly associated with idiopathic thrombotic thrombocytopenic purpura, as measured by estimated odds ratios (ORs) and 95% CIs. This study is registered with ClinicalTrials.gov, number NCT00426686. We enrolled 939 patients with adult-onset thrombotic thrombocytopenic purpura, of whom 772 (82%) patients had available data and samples at presentation and comprised the cohort of interest. The prevalence of thrombotic thrombocytopenic purpura in France was 13 cases per million people. At presentation, 378 (49%) patients had idiopathic thrombotic thrombocytopenic purpura, whereas 394 (51%) patients had disease associated with miscellaneous clinical situations (infections, autoimmunity, pregnancy, cancer, organ transplantation, and drugs). Pathophysiologically, three distinct forms of thrombotic thrombocytopenic purpura were observed: 585 (75%) patients had autoimmune disease with anti-ADAMTS13 IgG, 166 (22%) patients had acquired disease of unknown cause and 21 (3%) patients had inherited disease (Upshaw-Schulman syndrome) with mutations of the ADAMTS13 gene. Idiopathic thrombotic thrombocytopenic purpura were mainly autoimmune (345 [91%] cases), whereas non-idiopathic diseases were

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

    Science.gov (United States)

    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

  2. Seroprevalence of diphtheria toxoid IgG antibodies in children, adolescents and adults in Poland.

    Science.gov (United States)

    Zasada, Aleksandra A; Rastawicki, Waldemar; Rokosz, Natalia; Jagielski, Marek

    2013-11-19

    Recommendations for diphtheria immunization are to apply an effective primary immunization in infancy and to maintain immunity throughout life. Immunity against diphtheria depends primarily on antibody to the diphtheria toxin. This study evaluated the seroprevalence of IgG diphtheria antitoxin in sera of healthy children, adolescents and adults in Poland. A total of 1387 serum samples collected between 2010 and 2012 from individuals with ages ranging from 1 month to 85 years were investigated. Antibody concentrations were measured with an enzyme-linked immunosorbent assay (Anti-Diphtheria Toxoid ELISA IgG, Euroimmun, Germany). The results showed that among 1387 individuals examined, 547 (39.4%) had anti-diphtheria toxoid IgG antibody levels below 0.1 IU/ml (36.9% ≤ 18 years and 40.5% >18 years old, respectively). The 212 (50.8%) children and 542 (55.9%) adults showed only basic protection (0.1-1.0 IU/ml) and need immediate booster. High levels of anti-diphtheria toxoid IgG antibodies (>1.0 IU/ml) were found more often in children and adolescent (12.2%) than in adults (3.6%) and this was statistically significant (P 60 years old. Characteristically, in individuals > 40 years old high levels of anti-diphtheria toxoid IgG antibodies (>1.0 IU/ml) were not seen. There were no statistically significant differences in results in relation to gender. The present study showed inadequate immunity levels to diphtheria amongst the Polish population, especially in adults > 40 years old and children ≤ 2 years old. To prevent reemergence of diphtheria an information campaign reminding people about recommendations concerning diphtheria booster vaccination in adults should be conducted. Moreover, the immunogenicity of the DTP vaccine used in Poland should be verified.

  3. Pegylated Long-Acting Human Growth Hormone Possesses a Promising Once-Weekly Treatment Profile, and Multiple Dosing Is Well Tolerated in Adult Patients with Growth Hormone Deficiency

    DEFF Research Database (Denmark)

    Søndergaard, Esben; Klose, Marianne Christina; Hansen, Mette

    2011-01-01

    Background: Recombinant human GH (rhGH) replacement therapy in children and adults currently requires daily sc injections for several years or lifelong, which may be both inconvenient and distressing for patients. NNC126-0083 is a pegylated rhGH developed for once-weekly administration. Objectives......: Our objective was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple doses of NNC126-0083 in adult patients with GH deficiency (GHD). Subjects and Methods: Thirty-three adult patients with GHD, age 20-65 yr, body mass index 18.5-35.0 kg/m(2), and glycated...... to 240 h after the third dosing. Physical examination, antibodies, and local tolerability were assessed. Results: NNC126-0083 was well tolerated with no difference in local tolerability compared with placebo and with no signs of lipoatrophy. A more than dose-proportional exposure was observed...

  4. Zinc-deficiency acrodermatitis in a patient with chronic alcoholism and gastric bypass: a case report

    Directory of Open Access Journals (Sweden)

    Dariush Shahsavari

    2014-07-01

    Full Text Available Acquired adult-onset zinc deficiency is occasionally reported in patients with malnutrition states, such as alcoholism, or malabsorptive states, such as post-bariatric surgery. The defining symptoms of hypozincemia include a classic triad of necrolytic dermatitis, diffuse alopecia, and diarrhea. We report a case of zinc deficiency in a 39-year-old man with history of gastric bypass surgery and alcoholism. For this patient, severe hypozincemia confirmed acrodermatitis, and zinc supplementation was met with gradual improvement.

  5. Coronative antibody tires in sera of healthy adults and experimentally infected volunteers.

    Science.gov (United States)

    Bradburne, A F; Somerset, B A

    1972-06-01

    Six coronaviruses isolated in the U.S.A. have been inoculated into volunteers and all produced colds. Between 10 and 20% of infected volunteers developed heterologous antibody responses after these and other experimental infections with coronaviruses. The haemagglutination-inhibition test with the OC43 virus strain was found to detect antibody rises after infection with a variety of strains.Studies on normal adult sera taken between 1965 and 1970 revealed a high frequency of neutralizing antibody to one strain (229 E) and a frequency of HI antibody to strain OC43 which fluctuated from year to year. Complement-fixing antibodies to these two viruses were also found, revealing an apparent increase in the activity of coronaviruses in the general population of the U.K., during the winter of 1968-9.

  6. Intimal spindle cell sarcoma masquerading as adult-onset symptomatic pulmonic stenosis: a case report and review of the literature.

    Science.gov (United States)

    Manmadhan, Arun; Malhotra, Sunil P; Weinberg, Catherine R; Reyentovich, Alex; Latson, Larry A; Bhatla, Puneet; Saric, Muhamed

    2017-10-30

    Pulmonary artery intimal spindle cell sarcomas are rare and carry with them a poor prognosis and high rate of recurrence. In extremely rare cases, this tumor can infiltrate the pulmonic valve and manifest as adult-onset pulmonic stenosis. We report an unusual case of a patient with symptomatic, adult-onset severe pulmonic stenosis who was referred for possible balloon valvuloplasty but was subsequently found to have pulmonary artery intimal sarcoma infiltrating the pulmonary valve leading to progressive exertional dyspnea. The presence of adult-onset pulmonic stenosis should prompt the clinician to investigate further as most cases of pulmonic stenosis are congenital in nature and present early in life. Careful diagnostic evaluation in concert with multimodal imaging should take place to arrive at the correct and challenging diagnosis of sarcoma-induced adult-onset severe pulmonic stenosis. Given the poor prognosis and rapid progression of disease, early diagnosis is crucial.

  7. Immunohistochemical identification of messenger RNA-related proteins in basophilic inclusions of adult-onset atypical motor neuron disease.

    Science.gov (United States)

    Fujita, Kengo; Ito, Hidefumi; Nakano, Satoshi; Kinoshita, Yoshimi; Wate, Reika; Kusaka, Hirofumi

    2008-10-01

    This report concerns an immunohistochemical investigation on RNA-related proteins in the basophilic inclusions (BIs) from patients with adult-onset atypical motor neuron disease. Formalin-fixed, paraffin-embedded sections of the motor cortex and the lumbar spinal cord were examined. The BIs appeared blue in color with H&E and Nissl stain, and pink with methylgreen-pyronin stain. Ribonuclease pretreatment abolished the methylgreen-pyronin staining, suggesting that the BIs contained RNA. Immunohistochemically, the BIs were distinctly labeled with the antibodies against poly(A)-binding protein 1, T cell intracellular antigen 1, and ribosomal protein S6. These proteins are essential constituents of stress granules. In contrast, the BIs were not immunoreactive for ribosomal protein L28 and decapping enzyme 1, which are core components of transport ribonucleoprotein particles and processing bodies, respectively. Moreover, the BIs were not immunopositive for TDP-43. Our results imply that translation attenuation could be involved in the processes of BI formation in this disorder.

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

    Science.gov (United States)

    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.

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

    OpenAIRE

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

    2017-01-01

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

  10. Clinical and MRI features of supratentorial gliomas with adult-onset epilepsy

    International Nuclear Information System (INIS)

    Hashimoto, Takahiro; Yamaura, Akira; Watanabe, Osamu.

    1992-01-01

    Although some patients with supratentorial gliomas develop epilepsy in their clinical course, the details of adult-onset epilepsy with gliomas have not been fully evaluated. This paper reports on 15 cases of supratentorial glioma with the sole symptom of adult-onset epilepsy and characterizes their clinical and MRI features. The patients, 5 males and 10 females, developed the first epilepsy at the mean age of 37 years. Generalized seizure was encountered in all cases and focal seizure alone was never seen. Seizure was satisfactorily controlled with anticonvulsants in all except 2 cases. The tumor was located in the frontal lobe (9 cases) or temporal lobe (6 cases). Histologically, there were 12 astrocytomas, 2 glioblastomas, and 1 oligoastrocytoma. Of these, 12 were benign gliomas. Surprisingly, CT scan and MRI revealed tumors larger than predicted. The abnormal intensity region was delineated most prominently on T 2 -weighted SE image and was broader on T 2 -weighted spin echo image than on T 1 -weighted spin echo and inversion recovery image. The authors conclude that gliomas presenting with epilepsy tend to be histologically benign, are predominantly seen in middle-aged women, and are located in the frontal and temporal lobes. Although a tumor may be large enough to be detected on CT scan or MRI, as in the present study, histological examination is needed to establish the diagnosis. Additionally, gliomas with equivocal abnormalities on CT and MRI do evolve despite further neurological deficits, so meticulous evaluation including stereotactic biopsy is the method of choice. Finally, T 2 -weighted SE image in the coronal plane is advocated for patients with adult-onset epilepsy to achieve accurate diagnosis and to initiate early treatment. (author)

  11. VGKC complex antibodies in epilepsy: diagnostic yield and therapeutic implications.

    Science.gov (United States)

    Lilleker, James B; Jones, Matthew S; Mohanraj, Rajiv

    2013-11-01

    In a significant number of patients developing epilepsy in adult life, the aetiology of their seizures remains unclear. Antibodies directed against the voltage gated potassium channel complex (VGKC Ab) have been identified in various cohorts of patients with epilepsy, although the role of these antibodies in epilepsy pathogenesis is not fully known. We reviewed the notes of 144 patients with unexplained adult onset epilepsy who had been tested for VGKC Abs. We collected data on their clinical syndrome, investigation results and response to treatment. We identified 6 (4.2%) patients who had titres of >400 pM. One of the six patients was positive for LGI1 and another for CASPR2 subunit antibodies. All patients were given immunotherapy and experienced improvement in seizure control. No patient had the clinical syndrome of limbic encephalitis. Patients with otherwise unexplained epilepsy and positive VGKC Abs are a heterogeneous group. In our cohort there was an overall favourable response to immunotherapy but further prospective studies are needed to determine the significance of these antibodies and the optimum treatment regimen for patients. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2017-01-01

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

  13. Effects of Growth Hormone Replacement Therapy on Bone Mineral Density in Growth Hormone Deficient Adults: A Meta-Analysis

    OpenAIRE

    Xue, Peng; Wang, Yan; Yang, Jie; Li, Yukun

    2013-01-01

    Objectives. Growth hormone deficiency patients exhibited reduced bone mineral density compared with healthy controls, but previous researches demonstrated uncertainty about the effect of growth hormone replacement therapy on bone in growth hormone deficient adults. The aim of this study was to determine whether the growth hormone replacement therapy could elevate bone mineral density in growth hormone deficient adults. Methods. In this meta-analysis, searches of Medline, Embase, and The Cochr...

  14. A comparison of adolescent- and adult-onset first-episode, non-affective psychosis: 2-year follow-up

    DEFF Research Database (Denmark)

    Simonsen, Erik; Langeveld, Johannes; Joa, Inge

    2012-01-01

    This study aimed to compare 2-year outcome among individuals with early-onset (EO; clinical and treatment characteristics of 43 EO and 189 AO patients 2 years after their inclusion in a clinical epidemiologic...... no longer significant at the 2-year follow-up. This study challenges the findings of a larger and older literature base consisting primarily of non-comparative studies concluding that teenage onset indicates a poor outcome. Our results indicate that adolescent-onset and adult-onset psychosis have similar...... prognostic trajectories, although both may predict a qualitatively different course from childhood-onset psychosis....

  15. Intimal spindle cell sarcoma masquerading as adult-onset symptomatic pulmonic stenosis: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Arun Manmadhan

    2017-10-01

    Full Text Available Abstract Background Pulmonary artery intimal spindle cell sarcomas are rare and carry with them a poor prognosis and high rate of recurrence. In extremely rare cases, this tumor can infiltrate the pulmonic valve and manifest as adult-onset pulmonic stenosis. Case presentation We report an unusual case of a patient with symptomatic, adult-onset severe pulmonic stenosis who was referred for possible balloon valvuloplasty but was subsequently found to have pulmonary artery intimal sarcoma infiltrating the pulmonary valve leading to progressive exertional dyspnea. Conclusion The presence of adult-onset pulmonic stenosis should prompt the clinician to investigate further as most cases of pulmonic stenosis are congenital in nature and present early in life. Careful diagnostic evaluation in concert with multimodal imaging should take place to arrive at the correct and challenging diagnosis of sarcoma-induced adult-onset severe pulmonic stenosis. Given the poor prognosis and rapid progression of disease, early diagnosis is crucial.

  16. Thoracic CT findings of adult-onset still's disease: a case report

    International Nuclear Information System (INIS)

    Choi, Sun Young; Kim, Ki Jun; Lee, Jung Whee; Lee, Sung Yong; Hong, Yeon Sik

    2006-01-01

    Adult-onset of Still's disease is a rare systemic rheumatic disorder. It involves various organs including the lungs and pleura. We report here the CT findings of a patient with the thoracic manifestations of Still's disease, including axillary and mediastinal lymphadenopathies, pleural and pericardial effusions and infiltrations in both lung bases

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

    Science.gov (United States)

    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

  18. Chest radiographs in acquired antibody deficiency syndrome with chronic granulomatous inflammation

    International Nuclear Information System (INIS)

    Qaiyumi, S.A.A.; Peest, D.; Galanski, M.; Medizinische Hochschule Hannover

    1990-01-01

    Ten cases of acquired antibody deficiency syndrome with chronic granulomatous infection were diagnosed in our hospital during the past 10 years. We were able to perform a retrospective analysis of the initial and follow-up chest radiographs in 8 of these patients. The following pathological findings could be demonstrated: 1. increased bronchovascular markings in the basal lung fields, 2. reticular densities in the middle and basal lung fields, 3. confluent nodular densities of varying size in the periphery of the basal and middle fields, 4. pulmonary infiltrates in the middle and lower lobes, 5. hilar node enlargement of moderate extent. Findings 2, 3 and 5 completely disappeared under steroid therapy whereas 1 showed only partial recovery. If both the radiologic and serologic findings are considered, it is possible to differentiate this disease from sarcoidosis. (orig.) [de

  19. New onset of idiopathic bilateral ear tics in an adult.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  1. Tocilizumab for uncontrollable systemic inflammatory response syndrome complicating adult-onset Still disease

    Science.gov (United States)

    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

  2. Changes in bone mineral density, body composition, and lipid metabolism during growth hormone (GH) treatment in children with GH deficiency

    NARCIS (Netherlands)

    A.M. Boot (Annemieke); M.A. Engels (Melanie); G.J.M. Boerma (Geert); E.P. Krenning (Eric); S.M.P.F. de Muinck Keizer-Schrama (Sabine)

    1997-01-01

    textabstractAdults with childhood onset GH deficiency (GHD) have reduced bone mass, increased fat mass, and disorders of lipid metabolism. The aim of the present study was to evaluate bone mineral density (BMD), bone metabolism, body composition, and lipid metabolism in

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

    Science.gov (United States)

    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.

  4. Effects of Growth Hormone Replacement Therapy on Bone Mineral Density in Growth Hormone Deficient Adults: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Peng Xue

    2013-01-01

    Full Text Available Objectives. Growth hormone deficiency patients exhibited reduced bone mineral density compared with healthy controls, but previous researches demonstrated uncertainty about the effect of growth hormone replacement therapy on bone in growth hormone deficient adults. The aim of this study was to determine whether the growth hormone replacement therapy could elevate bone mineral density in growth hormone deficient adults. Methods. In this meta-analysis, searches of Medline, Embase, and The Cochrane Library were undertaken to identify studies in humans of the association between growth hormone treatment and bone mineral density in growth hormone deficient adults. Random effects model was used for this meta-analysis. Results. A total of 20 studies (including one outlier study with 936 subjects were included in our research. We detected significant overall association of growth hormone treatment with increased bone mineral density of spine, femoral neck, and total body, but some results of subgroup analyses were not consistent with the overall analyses. Conclusions. Our meta-analysis suggested that growth hormone replacement therapy could have beneficial influence on bone mineral density in growth hormone deficient adults, but, in some subject populations, the influence was not evident.

  5. Clinical and MRI features of supratentorial gliomas with adult-onset epilepsy

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Takahiro; Yamaura, Akira (Chiba Univ. (Japan). School of Medicine); Watanabe, Osamu

    1992-02-01

    Although some patients with supratentorial gliomas develop epilepsy in their clinical course, the details of adult-onset epilepsy with gliomas have not been fully evaluated. This paper reports on 15 cases of supratentorial glioma with the sole symptom of adult-onset epilepsy and characterizes their clinical and MRI features. The patients, 5 males and 10 females, developed the first epilepsy at the mean age of 37 years. Generalized seizure was encountered in all cases and focal seizure alone was never seen. Seizure was satisfactorily controlled with anticonvulsants in all except 2 cases. The tumor was located in the frontal lobe (9 cases) or temporal lobe (6 cases). Histologically, there were 12 astrocytomas, 2 glioblastomas, and 1 oligoastrocytoma. Of these, 12 were benign gliomas. Surprisingly, CT scan and MRI revealed tumors larger than predicted. The abnormal intensity region was delineated most prominently on T[sub 2]-weighted SE image and was broader on T[sub 2]-weighted spin echo image than on T[sub 1]-weighted spin echo and inversion recovery image. The authors conclude that gliomas presenting with epilepsy tend to be histologically benign, are predominantly seen in middle-aged women, and are located in the frontal and temporal lobes. Although a tumor may be large enough to be detected on CT scan or MRI, as in the present study, histological examination is needed to establish the diagnosis. Additionally, gliomas with equivocal abnormalities on CT and MRI do evolve despite further neurological deficits, so meticulous evaluation including stereotactic biopsy is the method of choice. Finally, T[sub 2]-weighted SE image in the coronal plane is advocated for patients with adult-onset epilepsy to achieve accurate diagnosis and to initiate early treatment. (author).

  6. Vitamin B12 deficiency might be related to sarcopenia in older adults.

    Science.gov (United States)

    Bulut, Esra Ates; Soysal, Pinar; Aydin, Ali Ekrem; Dokuzlar, Ozge; Kocyigit, Suleyman Emre; Isik, Ahmet Turan

    2017-09-01

    Sarcopenia and dynapenia are related to repeated falls, mobility restriction, depression, frailty, increased mortality and morbidity. The aim of this study is to evaluate the relationship between vitamin B12 deficiency and sarcopenia in older adults. 403 patients, who attended to outpatient clinic and underwent comprehensive geriatric assessment, were included study. All cases' skeletal muscle mass (SMM), walking speed and hand grip strength were recorded by bioimpedance, 4meter walking test and hand dynamometer respectively. The diagnosis of sarcopenia was defined according to the criteria of the European Working Group on Sarcopenia in Older People. Sarcopenia was accepted low SMM with low handgrip strength or low physical performance. Dynapenia was defined as handgrip strength sarcopenia and dynapenia was 24.8% and 32.0%, respectively. In the patients with sarcopenia, mean age, osteoporosis and frailty were higher, and MMSE, and instrumental ADL scores were lower than the patients without sarcopenia (psarcopenia and dynapenia were 31.6% and 35.4%, respectively, in patients with vitamin B12 levels Sarcopenia, which results in lots of negative clinical outcomes in older adults, might be related to vitamin B12 deficiency. Therefore, these patients should be periodically examined for vitamin B12 deficiency due to the potential negative clinical outcomes such as sarcopenia in older adults. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Unique DNA repair gene variations and potential associations with the primary antibody deficiency syndromes IgAD and CVID.

    Directory of Open Access Journals (Sweden)

    Steven M Offer

    Full Text Available BACKGROUND: Despite considerable effort, the genetic factors responsible for >90% of the antibody deficiency syndromes IgAD and CVID remain elusive. To produce a functionally diverse antibody repertoire B lymphocytes undergo class switch recombination. This process is initiated by AID-catalyzed deamination of cytidine to uridine in switch region DNA. Subsequently, these residues are recognized by the uracil excision enzyme UNG2 or the mismatch repair proteins MutSalpha (MSH2/MSH6 and MutLalpha (PMS2/MLH1. Further processing by ubiquitous DNA repair factors is thought to introduce DNA breaks, ultimately leading to class switch recombination and expression of a different antibody isotype. METHODOLOGY/PRINCIPAL FINDINGS: Defects in AID and UNG2 have been shown to result in the primary immunodeficiency hyper-IgM syndrome, leading us to hypothesize that additional, potentially more subtle, DNA repair gene variations may underlie the clinically related antibody deficiencies syndromes IgAD and CVID. In a survey of twenty-seven candidate DNA metabolism genes, markers in MSH2, RAD50, and RAD52 were associated with IgAD/CVID, prompting further investigation into these pathways. Resequencing identified four rare, non-synonymous alleles associated with IgAD/CVID, two in MLH1, one in RAD50, and one in NBS1. One IgAD patient carried heterozygous non-synonymous mutations in MLH1, MSH2, and NBS1. Functional studies revealed that one of the identified mutations, a premature RAD50 stop codon (Q372X, confers increased sensitivity to ionizing radiation. CONCLUSIONS: Our results are consistent with a class switch recombination model in which AID-catalyzed uridines are processed by multiple DNA repair pathways. Genetic defects in these DNA repair pathways may contribute to IgAD and CVID.

  8. Usual interstitial pneumonia in adult-onset still's disease

    International Nuclear Information System (INIS)

    Rodelo, Joaquin; Gonzalez, Luis Alonso; Velasquez, Monica Patricia; Vasquez, Gloria; Uribe, Oscar; Perez, Maria del Pilar; Ramirez, Luis Alberto

    2005-01-01

    Adult-onset still's disease (AOSD) is a multi-system inflammatory disorder of unknown origin, characterized by high spiking fevers, evanescent salmon colored rash, arthralgias or arthritis, hepatospleno-megaly, Iymphadenopathy and sore throat. It is not uncommon for AOSD to involve other organs, such as the liver, the kidney; the bone marrow and less often the lungs. Pulmonary involvement ranges from 30 to 40 % (0 to 53 %), the pulmonary manifestations of AOSD include pleurisy, acute pneumonitis and even the acute respiratory distress syndrome. We present a case of a patient with AOSD who developed an interstitial lung disease and reviewed the literature on it

  9. Transmitter release in the neuromuscular synapse of the protein kinase C theta-deficient adult mouse.

    Science.gov (United States)

    Besalduch, Núria; Santafé, Manel M; Garcia, Neus; Gonzalez, Carmen; Tomás, Marta; Tomás, Josep; Lanuza, Maria A

    2011-04-01

    We studied structural and functional features of the neuromuscular junction in adult mice (P30) genetically deficient in the protein kinase C (PKC) theta isoform. Confocal and electron microscopy shows that there are no differences in the general morphology of the endplates between PKC theta-deficient and wild-type (WT) mice. Specifically, there is no difference in the density of the synaptic vesicles. However, the myelin sheath is not as thick in the intramuscular nerve fibers of the PKC theta-deficient mice. We found a significant reduction in the size of evoked endplate potentials and in the frequency of spontaneous, asynchronous, miniature endplate potentials in the PKC theta-deficient neuromuscular preparations in comparison with the WT, but the mean amplitude of the spontaneous potentials is not different. These changes indicate that PKC theta has a presynaptic role in the function of adult neuromuscular synapses. Copyright © 2010 Wiley-Liss, Inc.

  10. Hepatic tuberculosis presenting with extreme hyperferritinemia masquerading as adult-onset Still’s disease: a case report

    Directory of Open Access Journals (Sweden)

    Manoj Edirisooriya

    2012-07-01

    Full Text Available Abstract Introduction Isolated hepatic tuberculosis is an uncommon manifestation of one of the most common infections worldwide, caused by Mycobacterium tuberculosis. Extremely high serum ferritin, which is regarded as a marker of adult onset Still’s disease, has not been observed in patients with tuberculosis of the liver. We report a case of hepatic tuberculosis who presented with clinical criteria of adult-onset Still’s disease and extreme hyperferritinemia, which posed a diagnostic confusion. Case presentation Our patient was a 48-year-old Sri Lankan man who presented with fever, polyarthralgia and a generalized skin rash of three months duration. He had marked constitutional symptoms, oral ulcers, hair loss, anemia and hepatomegaly. Laboratory investigations disclosed an inflammatory syndrome, evidence of hepatic dysfunction, bone marrow suppression and a raised serum ferritin level of 34,674 ng/ml. A rapidly deteriorating course of illness prompted treatment based on a presumptive diagnosis of adult-onset Still’s disease until liver histology was available. The patient died of sepsis followed by multi-organ dysfunction. Later, the liver histology revealed tuberculosis. Conclusion Extrapulmonary tuberculosis, although well known to present with peculiar manifestations, has not been reported to be associated with extremely high levels of serum ferritin in immunocompetent individuals. Isolated hepatic tuberculosis presenting with clinical criteria of adult-onset Still’s disease is remarkable. Since tuberculosis remains a potentially curable disease, an awareness of its’ protean manifestations is essential.

  11. The Clinical Significance of Specific Antibody Deficiency (SAD) Severity in Chronic Rhinosinusitis (CRS).

    Science.gov (United States)

    Keswani, Anjeni; Dunn, Neha M; Manzur, Angelica; Kashani, Sara; Bossuyt, Xavier; Grammer, Leslie C; Conley, David B; Tan, Bruce K; Kern, Robert C; Schleimer, Robert P; Peters, Anju T

    Despite the increased identification of specific antibody deficiency (SAD) in chronic rhinosinusitis (CRS), little is known about the relationship between SAD severity and the severity and comorbidities of CRS. The prevalence of an impaired antibody response in the general population is also unknown. The objective of this study was to determine if the SAD severity stratification applies to real-life data of patients with CRS. An electronic health record database was used to identify patients with CRS evaluated for humoral immunodeficiency with quantitative immunoglobulins and Streptococcus pneumoniae antibody titers before and after pneumococcal vaccine. SAD severity was defined, according to the guidelines, based on the numbers of titers ≥1.3 μg/dL after vaccination: severe (≤2 serotypes), moderate (3-6 serotypes), and mild (7-10 serotypes). Comorbidities and therapeutic response were assessed. The prevalence of an impaired antibody response in a normal population was assessed. Twenty-four percent of the patients with CRS evaluated for immunodeficiency had SAD, whereas 11% of a normal population had an impaired immune response to polysaccharide vaccination (P SAD. Twenty-four (10%) had severe SAD, 120 (50%) had moderate SAD, and 95 (40%) had mild SAD. Patients with moderate-to-severe SAD had worse asthma, a greater likelihood of pneumonia, and more antibiotic courses in the 2 years after vaccination than patients with mild SAD. This study provides real world data supporting stratification of SAD by severity, demonstrating a significant increase in the comorbid severity of asthma and infections in CRS patients with moderate-to-severe SAD compared with those with mild SAD and those without SAD. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  12. Developmental vitamin D deficiency alters MK-801-induced behaviours in adult offspring.

    Science.gov (United States)

    Kesby, James P; O'Loan, Jonathan C; Alexander, Suzanne; Deng, Chao; Huang, Xu-Feng; McGrath, John J; Eyles, Darryl W; Burne, Thomas H J

    2012-04-01

    Developmental vitamin D (DVD) deficiency is a candidate risk factor for developing schizophrenia in humans. In rodents DVD deficiency induces subtle changes in the way the brain develops. This early developmental insult leads to select behavioural changes in the adult, such as an enhanced response to amphetamine-induced locomotion in female DVD-deficient rats but not in male DVD-deficient rats and an enhanced locomotor response to the N-methyl-D: -aspartate (NMDA) receptor antagonist, MK-801, in male DVD-deficient rats. However, the response to MK-801-induced locomotion in female DVD-deficient rats is unknown. Therefore, the aim of the current study was to further examine this behavioural finding in male and female rats and assess NMDA receptor density. DVD-deficient Sprague Dawley rats were assessed for locomotion, ataxia, acoustic startle response (ASR) and prepulse inhibition (PPI) of the ASR to multiple doses of MK-801. The NMDA receptor density in relevant brain regions was assessed in a drug-naive cohort. DVD deficiency increased locomotion in response to MK-801 in both sexes. DVD-deficient rats also showed an enhanced ASR compared with control rats, but PPI was normal. Moreover, DVD deficiency decreased NMDA receptor density in the caudate putamen of both sexes. These results suggest that a transient prenatal vitamin D deficiency has a long-lasting effect on NMDA-mediated signalling in the rodent brain and may be a plausible candidate risk factor for schizophrenia and other neuropsychiatric disorders.

  13. Delayed onset of experimental autoimmune encephalomyelitis in Olig1 deficient mice.

    Directory of Open Access Journals (Sweden)

    Xiaoli Guo

    Full Text Available BACKGROUND: Olig1 is a basic helix-loop-helix (bHLH transcription factor that is essential for oligodendrogenesis and efficient remyelination. However, its role in neurodegenerative disorders has not been well-elucidated. METHODOLOGY/PRINCIPAL FINDINGS: Here we investigated the effects of Olig1 deficiency on experimental autoimmune encephalomyelitis (EAE, an animal model of multiple sclerosis (MS. We show that the mean disease onset of myelin oligodendrocyte glycoprotein (MOG-induced EAE in Olig1(-/- mice is significantly slower than wide-type (WT mice (19.8 ± 2.2 in Olig1(-/- mice and 9.5 ± 0.3 days in WT mice. In addition, 10% of Olig1(-/- mice did not develop EAE by the end of the observation periods (60 days. The severity of EAE, the extent of demyelination, and the activation of microglial cells and astrocytes in spinal cords, were significantly milder in Olig1(-/- mice compared with WT mice in the early stage. Moreover, the visual function, as assessed by the second-kernel of multifocal electroretinograms, was better preserved, and the number of degenerating axons in the optic nerve was significantly reduced in Olig1(-/- mice. Interestingly, Olig1 deficiency had no effect on T cell response capability, however, it reduced the expression of myelin proteins such as MOG, myelin basic protein (MBP and myelin-associated glycoprotein (MAG. The expression of Olig2 remained unchanged in the optic nerve and brain, and it was reduced in the spinal cord of Olig1(-/- mice. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the Olig1 signaling pathways may be involved in the incidence rate and the severity of neurological symptoms in MS.

  14. In-Depth Analysis of Human Neonatal and Adult IgM Antibody Repertoires

    Directory of Open Access Journals (Sweden)

    Binbin Hong

    2018-02-01

    Full Text Available Although high-throughput sequencing and associated bioinformatics technologies have enabled the in-depth, sequence-based characterization of human immune repertoires, only a few studies on a relatively small number of sequences explored the characteristics of antibody repertoires in neonates, with contradictory conclusions. To gain a more comprehensive understanding of the human IgM antibody repertoire, we performed Illumina sequencing and IMGT/HighV-QUEST analysis of IgM heavy chain repertoire of the B lymphocytes from the cord blood (CB of neonates, as well as the repertoire from peripheral blood of healthy human adults (HH. The comparative study revealed unexpectedly high levels of similarity between the neonatal and adult repertoires. In both repertoires, the VDJ gene usage showed no significant difference, and the most frequently used VDJ gene was IGHV4-59, IGHD3-10, and IGHJ3. The average amino acid (aa length of CDR1 (CB: 8.5, HH: 8.4 and CDR2 (CB: 7.6, HH: 7.5, as well as the aa composition and the average hydrophobicity of the CDR3 demonstrated no significant difference between the two repertories. However, the average aa length of CDR3 was longer in the HH repertoire than the CB repertoire (CB: 14.5, HH: 15.5. Besides, the frequencies of aa mutations in CDR1 (CB: 19.33%, HH: 25.84% and CDR2 (CB: 9.26%, HH: 17.82% were higher in the HH repertoire compared to the CB repertoire. Interestingly, the most prominent difference between the two repertoires was the occurrence of N2 addition (CB: 64.87%, HH: 85.69%, a process that occurs during V-D-J recombination for introducing random nucleotide additions between D- and J-gene segments. The antibody repertoire of healthy adults was more diverse than that of neonates largely due to the higher occurrence of N2 addition. These findings may lead to a better understanding of antibody development and evolution pathways and may have potential practical value for facilitating the generation of more

  15. Neutralizing antibody response in the patients with hand, foot and mouth disease to enterovirus 71 and its clinical implications

    Directory of Open Access Journals (Sweden)

    Zhu Liye

    2011-06-01

    Full Text Available Abstract Enterovirus 71 (EV71 has emerged as a significant pathogen causing large outbreaks in China for the past 3 years. Developing an EV71 vaccine is urgently needed to stop the spread of the disease; however, the adaptive immune response of humans to EV71 infection remains unclear. We examined the neutralizing antibody titers in HFMD patients and compared them to those of asymptomatic healthy children and young adults. We found that 80% of HFMD patients became positive for neutralizing antibodies against EV71 (GMT = 24.3 one day after the onset of illness. The antibody titers in the patients peaked two days (GMT = 79.5 after the illness appeared and were comparable to the level of adults (GMT = 45.2. Noticeably, the antibody response was not correlated with disease severity, suggesting that cellular immune response, besides neutralizing antibodies, could play critical role in controlling the outcome of EV71 infection in humans.

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

    Science.gov (United States)

    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.

  17. Vitamin D deficiency: knowledge and practices among the adult population in Sharjah, United Arab Emirates.

    Science.gov (United States)

    Salmanpour, Vida A; Ibrahim, Hassan S; Salameh, Ahmad G; Yahya, Amel M; Debal, Basel K

    2016-01-01

    Research demonstrate that vitamin D deficiency is significantly associated with bone diseases (e.g., osteoporosis), muscle cramps, back pain, heart diseases, diabetes mellitus, etc. The lack of knowledge and poor practice of study subjects regarding vitamin D deficiency became evident in this study. Vitamin D is vital for the growth and development of the body throughout the life span. The aim of this study is to investigate the knowledge and the practices related to vitamin D deficiency among the adult population in Sharjah, UAE. A cross-sectional study was conducted among adults aged 20-40 years in Sharjah, UAE. Participants were selected from public places using convenience sampling method. They were subjected to a self-administered questionnaire. Data was analyzed using SPSS 20 software. All knowledge-related questions were summed up, where a correct answer was given 1 point and incorrect one a 0, yielding a score out of 43. Subjects' scores were then transformed to a percentage. A total of 503 adults were included in the study. They had a mean age of 30 years (±5.47) with a relatively homogenous gender distribution (51 % females). The mean knowledge score on vitamin D deficiency was 16.7 out of 43 (39 %). Less than half of the respondents (43 %) knew that sunlight is the main source of vitamin D. The mean score for participants' practice was 2.34 out of 6 (39 %); 77 % of them reported that they tried to avoid sun exposure, and 97 % had not tested vitamin D levels in their blood before. The majority of the adults demonstrated significant lack of knowledge and poor practices towards vitamin D and its deficiency. Therefore, attempts to increase the awareness about this issue are required through establishing educational campaigns targeting the general public in Sharjah, UAE.

  18. 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.

    Science.gov (United States)

    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.

  19. Vitamin D Deficiency and Cardiometabolic Risks: A Juxtaposition of Arab Adolescents and Adults.

    Science.gov (United States)

    Al-Daghri, Nasser M; Al-Saleh, Yousef; Aljohani, Naji; Alokail, Majed; Al-Attas, Omar; Alnaami, Abdullah M; Sabico, Shaun; Alsulaimani, Maha; Al-Harbi, Mohammed; Alfawaz, Hanan; Chrousos, George P

    2015-01-01

    The recent exponential surge in vitamin D research reflects the global epidemic of vitamin D deficiency and its potential impact on several chronic diseases in both children and adults. Several subpopulations, including Arab adolescent boys and girls, remain understudied. This study aims to fill this gap. A total of 2225 apparently healthy Saudi adolescents (1187 boys and 1038 girls, aged 13-17 years old) and 830 adults (368 men and 462 women, aged 18-50 years old) were respectively recruited from different public schools and medical practices within Riyadh, Saudi Arabia. Anthropometrics were taken and fasting blood samples withdrawn to examine serum glucose and lipid profile by routine analysis and 25-hydroxyvitamin D by ELISA. Almost half of the girls (47.0%) had vitamin D deficiency as compared to only 19.4% of the boys (pArab adolescents. Vitamin D deficiency is mostly associated with cardiometabolic risk factors in adolescent Arab boys. This indicates a sex- and age-related disadvantage for boys with low vitamin D status and challenges the extra-skeletal protection of vitamin D correction in adolescent females.

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

    Science.gov (United States)

    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 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.

  1. Clinical study on antibody-associated limbic encephalitis

    Directory of Open Access Journals (Sweden)

    WANG Jia-wei

    2013-01-01

    Full Text Available In recent years, the antibody-associated limbic encephalitis (LE has attracted attentions of more and more clinicians. The associated antibodies mainly act on neuronal cell surface antigens, including the N-methyl-D-aspartate (NMDA receptor, the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA receptor, the γ-aminobutyric acid B (GABAB receptor, leucine-rich glioma-inactivated 1 (LGI1 and contactin-associated protein-like 2 (Caspr2 and so on. The clinical manifestation is primarily defined by the subacute onset of short-term memory loss, seizures, confusion and psychiatric symptoms suggesting the involvement of the limbic system. These severe and protracted disorders can affect children and young adults, occurring with or without tumor association. Routine detection of serum and cerebrospinal fluid (CSF and imaging tests show no specificity, but associated antibodies can be detected in serum and (or CSF. The patients respond well to tumor resection and immunotherapies, including corticosteroids, intravenous immunoglobulin (IVIg, plasma exchange or combination of them, but may relapse. This article aims to study the clinical features and treatment of antibody-associated limbic encephalitis and to improve the diagnosis and prognosis of these diseases.

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

    Science.gov (United States)

    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…

  3. Advances in clinical determinants and neurological manifestations of B vitamin deficiency in adults.

    Science.gov (United States)

    Sechi, GianPietro; Sechi, Elia; Fois, Chiara; Kumar, Neeraj

    2016-05-01

    B vitamin deficiency is a leading cause of neurological impairment and disability throughout the world. Multiple B vitamin deficiencies often coexist, and thus an understanding of the complex relationships between the different biochemical pathways regulated in the brain by these vitamins may facilitate prompter diagnosis and improved treatment. Particular populations at risk for multiple B vitamin deficiencies include the elderly, people with alcoholism, patients with heart failure, patients with recent obesity surgery, and vegetarians/vegans. Recently, new clinical settings that predispose individuals to B vitamin deficiency have been highlighted. Moreover, other data indicate a possible pathogenetic role of subclinical chronic B vitamin deficiency in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. In light of these findings, this review examines the clinical manifestations of B vitamin deficiency and the effect of B vitamin deficiency on the adult nervous system. The interrelationships of multiple B vitamin deficiencies are emphasized, along with the clinical phenotypes related to B vitamin deficiencies. Recent advances in the clinical determinants and diagnostic clues of B vitamin deficiency, as well as the suggested therapies for B vitamin disorders, are described. © The Author(s) 2016. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. Progressive Retinal Degeneration and Accumulation of Autofluorescent Lipopigments in Progranulin Deficient Mice

    Science.gov (United States)

    Hafler, Brian P.; Klein, Zoe A.; Zhou, Z. Jimmy; Strittmatter, Stephen M.

    2014-01-01

    Prior investigations have shown that patients with neuronal ceroid lipofuscinosis (NCL) develop neurodegeneration characterized by vision loss, motor dysfunction, seizures, and often early death. Neuropathological analysis of patients with NCL shows accumulation of intracellular autofluorescent storage material, lipopigment, throughout neurons in the central nervous system including in the retina. A recent study of a sibling pair with adult onset NCL and retinal degeneration showed linkage to the region of the progranulin (GRN) locus and a homozygous mutation was demonstrated in GRN. In particular, the sibling pair with a mutation in GRN developed retinal degeneration and optic atrophy. This locus for this form of adult onset neuronal ceroid lipofuscinosis was designated neuronal ceroid lipofuscinosis-11 (CLN11). Based on these clinical observations, we wished to determine whether Grn-null mice develop accumulation of autofluorescent particles and retinal degeneration. Retinas of both wild-type and Progranulin deficient mice were examined by immunostaining and autofluorescence. Accumulation of autofluorescent material was present in Progranulin deficient mice at 12 months. Degeneration of multiple classes of neurons including photoreceptors and retinal ganglion cells was noted in mice at 12 and 18 months. Our data shows that Grn−/− mice develop degenerative pathology similar to features of human CLN11. PMID:25234724

  5. Is late-onset OCD a distinct phenotype? Findings from a comparative analysis of "age at onset" groups.

    Science.gov (United States)

    Sharma, Eesha; Sundar, A Shyam; Thennarasu, Kandavel; Reddy, Y C Janardhan

    2015-10-01

    Significant differences in clinical profile and comorbidity patterns have been observed between "juvenile-onset" and "adult-onset" obsessive-compulsive disorder (OCD). There is little systematic research on onset of OCD after the fourth decade. The current study aims to compare the demographic, clinical, and comorbidity patterns of patients with "juvenile-onset" (OCD. Eight hundred two consecutive patients who consulted a specialty OCD clinic at a tertiary care hospital in India were evaluated with the Mini International Neuropsychiatric Interview, the Yale-Brown Obsessive-Compulsive Scale, and the Clinical Global Impression scale. 37.4%, 57.4%, and 5.2% of patients had juvenile-, adult-, and late-onset OCD, respectively. Late-onset OCD was associated with female gender (χ2=42, pOCD in first-degree relatives (χ2=20.4, pOCD was significantly associated with female gender, collecting compulsions, and less aggressive obsessions, in comparison with adult-onset OCD. In comparison with juvenile-onset, late-onset OCD was significantly associated with female gender, presence of precipitating factors, and less aggressive obsessions, sexual obsessions, and repeating compulsions. Late-onset OCD is characterized by female gender, lesser familial loading for OCD, and presence of precipitating factors, suggesting that it may have a distinct pathophysiology compared to juvenile- and adult-onset OCD. Systematic research is required to understand the family-genetic, neuropsychological, and neurobiological correlates of late-onset OCD.

  6. Mismatch Repair Deficiency Testing in Patients With Colorectal Cancer and Nonadherence to Testing Guidelines in Young Adults.

    Science.gov (United States)

    Shaikh, Talha; Handorf, Elizabeth A; Meyer, Joshua E; Hall, Michael J; Esnaola, Nestor F

    2018-02-08

    Mismatch repair (MMR) deficiency of DNA has been observed in up to 15% of sporadic colorectal cancers (CRCs) and is a characteristic feature of Lynch syndrome, which has a higher incidence in young adults (age, testing in adults with CRC and analyze nonadherence to long-standing testing guidelines in younger adults using a contemporary national data set to help identify potential risk factors for nonadherence to newly implemented universal testing guidelines. Adult (age, testing status were identified using the National Cancer Database. The study was conducted from March 16, 2016, to March 1, 2017. Patient sociodemographic, facility, tumor, and treatment characteristics. The primary outcome of interest was receipt of MMR deficiency testing. Multivariable logistic regression was used to identify independent predictors of testing in adult and/or young adult patients. A total of 152 993 adults with CRC were included in the study (78 579 [51.4%] men; mean [SD] age, 66.9 [13.9] years). Of these patients, only 43 143 (28.2%) underwent MMR deficiency testing; the proportion of patients tested increased between 2010 and 2012 (22.3% vs 33.1%; Ptesting; the proportion tested increased between 2010 and 2012 (36.1% vs 48.0%; P testing, whereas older age (OR, 0.31; 95% CI, 0.26-0.37); Medicare (OR, 0.89; 95% CI, 0.84-0.95), Medicaid (OR, 0.83; 95% CI, 0.73-0.93), or uninsured (OR, 0.78; 95% CI, 0.66-0.92) status; nonacademic vs academic/research facility type (OR, 0.44; 95% CI, 0.34-0.56); rectosigmoid or rectal tumor location (OR, 0.76; 95% CI, 0.68-0.86); unknown grade (OR, 0.61; 95% CI, 0.53-0.69); and nonreceipt of definitive surgery (OR, 0.33; 95% CI, 0.30-0.37) were associated with underuse of MMR deficiency testing. Despite recent endorsement of universal use of MMR deficiency testing in patients with CRC and well-established guidelines aimed at high-risk populations, overall utilization of testing is poor and significant underuse of testing among young adults

  7. Adult outcomes following amputation or lengthening for fibular deficiency.

    Science.gov (United States)

    Walker, Janet L; Knapp, Dwana; Minter, Christin; Boakes, Jennette L; Salazar, Juan Carlos; Sanders, James O; Lubicky, John P; Drvaric, David M; Davids, Jon R

    2009-04-01

    Fibular deficiency results in a small, unstable foot and ankle as well as a limb-length discrepancy. The purpose of this study was to assess outcomes in adults who, as children, had had amputation or limb-lengthening, commonly used treatments for fibular deficiency. Retrospective review of existing data collected since 1950 at six pediatric orthopaedic centers identified 248 patients with fibular deficiency who were twenty-one years of age or older at the time of the review. Excluding patients with other anomalies and other treatments (with the excluded group including six who had had lengthening and then amputation), we identified ninety-eight patients who had had amputation or limb-lengthening for the treatment of isolated unilateral fibular deficiency. Sixty-two patients (with thirty-six amputations and twenty-six lengthening procedures) completed several questionnaires, including one asking general demographic questions, the Beck Depression Inventory-II, the Quality of Life Questionnaire, and the American Academy of Orthopaedic Surgeons Lower Limb Questionnaire including the Short Form-36. A group of twenty-eight control subjects completed the Beck Depression Inventory-II and the Quality of Life Questionnaire. There were forty men and twenty-two women. The average age at the time of the interview was thirty-three years. There were more amputations in those with fewer rays and less fibular preservation. Lengthening resulted in more surgical procedures (6.3 compared with 2.4 in patients treated with amputation) and more days in the hospital (184 compared with sixty-three) (both pemployment, income, public assistance or disability payments, pain or use of pain medicine, sports participation, activity restriction, comfort wearing shorts, dislike of limb appearance, or satisfaction with treatment. No patient who had been treated for fibular deficiency reported signs of depression. The only significant difference between treatment groups shown by the Quality of Life

  8. Adult-Onset Type 1 Diabetes and Pregnancy: Three Case Reports

    OpenAIRE

    Bonsembiante, Barbara; Dalfrà, Maria Grazia; Masin, Michela; Gallo, Alessandra; Lapolla, Annunziata

    2013-01-01

    From 5% to 10% of diabetic patients have type 1 diabetes. Here we describe three cases of adult-onset type 1 diabetes in pregnancy treated at our clinic between 2009 and 2012. Two patients came for specialist examination during pregnancy, the third after pregnancy. These women had no prior overt diabetes and shared certain characteristics, that is, no family diabetes history, age over 35, normal prepregnancy BMI, need for insulin therapy as of the early weeks of pregnancy, and high-titer anti...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  11. Endocrine Disruptor Vinclozolin Induced Epigenetic Transgenerational Adult-Onset Disease

    Science.gov (United States)

    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

  12. Cognition and event-related potentials in adult-onset non-demented myotonic dystrophy type 1.

    Science.gov (United States)

    Tanaka, H; Arai, M; Harada, M; Hozumi, A; Hirata, K

    2012-02-01

    To clarify the cognitive and event-related potentials (ERPs) profiles of adult-onset genetically-proven non-demented myotonic dystrophy type 1 (DM1). Fourteen DM1 patients and matched 14 normal controls were enrolled. DM1 patients were compared with normal controls, using a variety of neuropsychological tests; an auditory "oddball" counting paradigm for the ERPs, and low-resolution brain electromagnetic tomography (LORETA). For patients, ERPs and neuropsychological parameters were correlated with CTG repeat size, duration of illness, grip strength, and arterial blood gas analysis. Frontal lobe dysfunction, prolonged N1 latency, and attenuated N2/P3 amplitudes were observed in DM1. Longer CTG repeat size was associated with fewer categories achieved on Wisconsin Card Sorting Test. Greater grip strength was associated with better scores on color-word "interference" of Stroop test. P3 latency was negatively correlated with PaO(2). LORETA revealed significant hypoactivities at the orbitofrontal and medial temporal lobe, cingulate, and insula. There was no correlation between ERPs and CTG expansion. Adult-onset non-demented DM1 presented frontal lobe dysfunction. Absence of correlations between CTG repeat size and objective ERP parameters suggested CTG expansion in lymphocytes does not directly contribute to cognitive dysfunction. CTG expansion in lymphocytes does not directly contribute to cognitive dysfunction of adult-onset non-demented DM1. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  13. Symptoms and findings in adult-onset celiac disease in a historical Danish patient cohort.

    Science.gov (United States)

    Schøsler, Louise; Christensen, Lisbet A; Hvas, Christian L

    2016-03-01

    The presentation of celiac disease (CD) has changed over the past decades. We aimed to describe the incidence of CD and its complications at diagnosis in a historical cohort in a well-defined population in Denmark. We included all patients aged 15+ years, who lived in Aarhus County, Denmark, and who were diagnosed with CD between January 2008 and August 2013. Data regarding gastrointestinal symptoms, anthropometrics, biochemistry, and bone mineral density were retrieved from patient records. A total of 93 patients with a valid CD diagnosis were identified, corresponding to an incidence rate of 6.4 per 100,000 person-years. At diagnosis, diarrhea and weight loss occurred in 54% and 47% patients, respectively. In total, 30% had anemia; 40%, iron deficiency; 20%, folate deficiency; and 17%, vitamin B12 deficiency. Vitamin D deficiency was present in 34%. In 28%, bone mineral density was determined during the first year after diagnosis. Of these, 54% had osteopenia and 12% osteoporosis. After introduction of a gluten-free diet, 28% had normalized transglutaminase antibody levels after 6 months, and 56% did after 12 months. Diabetes mellitus type 1 was present in 7%; dermatitis herpetiformis, in 3%; and thyroid dysfunction, in 5%. Only half of newly diagnosed CD patients presented with classic gastrointestinal symptoms. Anemia and vitamin deficiencies were common. Bone mineral density was determined in less than a third of the patients, and osteoporosis occurred in 12% of these. Serologic markers of CD normalized in approximately half of patients during the first year after the diagnosis.

  14. Diphtheria outbreak in Thailand, 2012; seroprevalence of diphtheria antibodies among Thai adults and its implications for immunization programs.

    Science.gov (United States)

    Wanlapakorn, Nasamon; Yoocharoen, Pornsak; Tharmaphornpilas, Piyanit; Theamboonlers, Apiradee; Poovorawan, Yong

    2014-09-01

    An age distribution shift in diphtheria cases during a 2012 outbreak in northeastern of Thailand suggests adults are increasingly at risk for infection in Thailand. Data regarding immunity against diphtheria among the adult Thai population is limited. We review a 2012 diphtheria outbreak in Thailand and conducted a nationwide seroepidemiological survey to determine the prevalence of diphtheria antibodies among Thai adults in order to inform immunization programs. A total of 41 confirmed cases, 6 probable cases and 101 carriers of diphtheria were reported from northeastern and upper southern Thailand. The diphtheria outbreak in northeastern Thailand occurred among adults aged > or =15 years; sporadic cases occurred among children from upper southern Thailand. We conducted a seroepidemiological survey of 890 Thai adults from 4 age groups (20-29, 30-39, 40-49 and 50-59 years) in 7 different geographical areas of Thailand (Chiang Mai, Ratchaburi, Chon Buri, Nakhon Si Thammarat, Phitsanulok, Khon Kaen and Songkhla). Diptheria toxin antibody levels were measured with a commercially available ELISA test. The seroprotection rate ranged from 83% to 99%, with the highest in eastern Thailand (Chon Buri, 99%) and the lowest in northern Thailand (Chiang Mai, 83%). Diphtheria antibodies declined with increasing age. We recommend one doseof diphtheria-tetanus toxoid (dT) vaccine once after 20 years of age in order to boost the antibody and revaccinations every 10 years to prevent future outbreaks.

  15. Are Patients with Childhood Onset of Insomnia and Depression More Difficult to Treat Than Are Those with Adult Onsets of These Disorders? A Report from the TRIAD Study

    Science.gov (United States)

    Edinger, Jack D.; Manber, Rachel; Buysse, Daniel J.; Krystal, Andrew D.; Thase, Michael E.; Gehrman, Phillip; Fairholme, Christopher P.; Luther, James; Wisniewski, Stephen

    2017-01-01

    Study Objectives: To determine if patients with childhood onsets (CO) of both major depression and insomnia disorder show blunted depression and insomnia treatment responses to concurrent interventions for both disorders compared to those with adult onsets (AO) of both conditions. Methods: This study was a secondary analysis of data obtained from a multisite randomized clinical trial designed to test the efficacy of combining a psychological/behavior insomnia therapy with antidepressant medication to enhance depression treatment outcomes in patients with comorbid major depression and insomnia. This study included 27 adults with CO of depression and insomnia and 77 adults with AO of both conditions. They underwent a 16-week treatment including: (1) a standardized two-step pharmacotherapy for depression algorithm, consisting of escitalopram, sertraline, and desvenlafaxine in a prescribed sequence; and (2) either cognitive behavioral insomnia therapy (CBT-I) or a quasi-desensitization control (CTRL) therapy. Main outcome measures were the 17-item Hamilton Rating Scale for Depression (HRSD-17) and the Insomnia Severity Index (ISI) completed pre-treatment and every 2 weeks thereafter. Results: The AO and CO groups did not differ significantly in regard to their pre-treatment HRSD-17 and ISI scores. Mixed model analyses that adjusted for the number of insomnia treatment sessions attended showed that the AO group achieved significantly lower, subclinical scores on the HRSD-17 and ISI than did the CO group by the time of study exit. Moreover, a significant group by treatment arm interaction suggested that HRSD-17 scores at study exit remained significantly higher in the CO group receiving the CTRL therapy than was the case for the participants in the CO group receiving CBT-I. Greater proportions of the AO group achieved a priori criteria for remission of insomnia (49.3% vs. 29.2%, p = 0.04) and depression (45.5% vs. 29.6%, p = 0.07) than did those in the CO group

  16. [Adult T-cell leukemia/lymphoma associated with unusual positivity of anti-ATLA (adult T-cell leukemia-cell-associated antigen) antibodies].

    Science.gov (United States)

    Eto, T; Okamura, H; Okamura, T; Gondo, H; Kudo, J; Shibuya, T; Harada, M; Niho, Y

    1990-03-01

    A 56-year-old female was admitted because of generalized lymphadenopathy. Based upon histological findings of biopsied lymph node, malignant lymphoma, diffuse large cell type was diagnosed. The surface marker analysis showed that malignant cells were positive for CD4 and CD2 but negative for CD8. Although anti-ATLA (adult T-cell leukemia associated antigen) antibody was negative with the use of a gelatin particle agglutination method (P.A.), other methods such as an indirect immunofluorescence assay (I.F.), an enzyme-linked immunosorbent assay (E.I.A.) and a Western blotting assay revealed the positivity for anti-ATLA antibody. Adult T-cell leukemia/lymphoma (ATL/L) was confirmed by the presence of monoclonal integration of HTLV-I proviral DNA in biopsied specimen. This case, showing a pattern of P.A. (-) and I.F. (+), is extremely unusual, because I.F. and P.A. show highly close correlation. Thus, it is important to employ different methods for screening of anti-ATLA antibodies in the diagnosis of ATL/L.

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

    Science.gov (United States)

    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 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.

  18. Immune-mediated steroid-responsive epileptic spasms and epileptic encephalopathy associated with VGKC-complex antibodies.

    Science.gov (United States)

    Suleiman, Jehan; Brenner, Tanja; Gill, Deepak; Troedson, Christopher; Sinclair, Adriane J; Brilot, Fabienne; Vincent, Angela; Lang, Bethan; Dale, Russell C

    2011-11-01

    Autoantibodies that bind to voltage-gated potassium-channel complex proteins (VGKC-complex antibodies) occur frequently in adults with limbic encephalitis presenting with cognitive impairment and seizures. Recently, VGKC-complex antibodies have been described in a few children with limbic encephalitis, and children with unexplained encephalitis presenting with status epilepticus. We report a case of infantile-onset epileptic spasms and developmental delay compatible with epileptic encephalopathy. Our patient was a female infant, aged 4 months at presentation. She had evidence of immune activation in the central nervous system with elevated cerebrospinal fluid neopterin and mirrored oligoclonal bands, which prompted testing for autoantibodies. VGKC-complex antibodies were elevated (201 pmol/L, normalVGKC-complex antibodies might represent a marker of immune therapy responsiveness in a subgroup of patients with infantile epileptic encephalopathy. © The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.

  19. Relationship Between Vitamin D Deficiency and Markers of Metabolic Syndrome Among Overweight and Obese Adults.

    Science.gov (United States)

    Kaseb, Fatemeh; Haghighyfard, Kimia; Salami, Maryam-Sadat; Ghadiri-Anari, Akram

    2017-06-01

    In recent years, metabolic syndrome, obesity, diabetes and cardiovascular disease has had a tremendous elevation growth. Many studies have demonstrated negative correlation between vitamin D deficiency and indexes of metabolic syndrome in obese patients. This study was designed to find the relation between vitamin D deficiency and markers of metabolic syndrome among overweight and obese adults referred to obesity center of Shahid Sadoughi hospital in 2014. Eighty-nine overweight and obese adults (79 women and 10 men), who 13 subjects were overweight and 76 subjects were obese were recruited in this cross-sectional study. Total cholesterol, high-density lipoprotein cholesterol, triglyceride, plasma glucose and vitamin D were measured. IDF criteria were used for identifying subjects with metabolic syndrome. Demographic questionnaire was completed. Statistical analysis was performed using SPSS version 16.0. Fisher exact test, logistic regression, and Spearman correlation coefficient were used. The frequency of vitamin D deficiency was 93.2%. According to IDF criteria, the frequency of metabolic syndrome was 36%. There was no significant relationship between vitamin D deficiency and metabolic syndrome. Among metabolic syndrome indicators, there was a significant direct relationship between vitamin D level with FBS (P=0.013) and SBP (P=0.023). There was no significant relationship between vitamin D deficiency and metabolic syndrome. Due to the lack of relationship between vitamin D deficiency and metabolic syndrome, small number of participants in this study and very low case of normal vitamin D level, further studies are needed.

  20. Body composition and metabolic profile in adults with vitamin D deficiency

    Directory of Open Access Journals (Sweden)

    Liane Murari ROCHA

    Full Text Available ABSTRACT Objective: To investigate the body composition and metabolic profile in individuals in terms of different concentrations of serum vitamin D, ranging from deficiency to sufficiency. Methods: A cross-sectional study of 106 adults of both genders, who were divided into three groups according to vitamin D levels: deficiency: <20ng/mL; insufficiency: 20-29.9ng/mL; and sufficiency: 30-100ng/mL. Anthropometric evaluation included weight, height, and body circumferences. Fat mass and lean mass were assessed using the Tetrapolar bioelectrical impedance method. Clinical and biochemical evaluations were also carried out. Insulin resistance was estimated using the Homeostasis Model Assessment Insulin index. Results: The analysis showed that the main alterations in individuals in the vitamin D deficiency group were higher triglycerides, very low density lipoprotein - cholesterol, fasting blood glucose, insulin, glycated hemoglobin, body mass index, body fat percentage, lean mass percentage, waist circumference, and Homeostasis Model Assessment Insulin than those of the vitamin D sufficient group (p<0.05. Conclusion: It was found that vitamin D deficiency causes important body composition and metabolic changes, which may lead to diseases such as diabetes Mellitus and metabolic syndrome.

  1. Vitamin D deficiency in older adults and its associated factors: a cross-sectional analysis of the Mexican Health and Aging Study.

    Science.gov (United States)

    Carrillo-Vega, María Fernanda; García-Peña, Carmen; Gutiérrez-Robledo, Luis Miguel; Pérez-Zepeda, Mario Ulises

    2017-12-01

    Vitamin D deficiency was common in older adults from a country with adequate sun exposure. The variables associated with this deficiency provide insight into the next steps needed to characterize older adults with this deficiency and to treat it accordingly. The aim of this study was to describe the prevalence of and factors associated with vitamin D deficiency among Mexican older adults. This was a secondary analysis of the last wave of the Mexican Health and Aging Study. Vitamin D levels along with other biomarkers were obtained from a sub-sample of Mexican adults older than 60 years. Prevalence was described by sex and age group, and a multivariate analysis was performed to test the factors associated with this condition. Data from 1088 adults over the age of 60 years were analyzed. The mean serum vitamin D level was 23.1 ± 8.1 ng/mL and was significantly higher among men than women (25.6 ± 0.6 and 22.8 ± 0.5 ng/mL, respectively; p vitamin D deficiency, 65% of whom were women. Low 25-(OH)-vitamin D levels were associated with female sex (OR 1.74, 95% CI 1.59-2.42), current smoking (OR 2.21, 95% CI 1.47-3.39), education (OR 1.1, 95% CI 1.06-1.13), physical activity (OR 1.74, 95% CI 1.31-2.23), and high levels of glycated hemoglobin (OR 1.16, 95% CI 1.07-1.25). Vitamin D deficiency was highly prevalent in Mexican older adults and was associated with a number of factors, indicating the multifactorial causality of this deficiency.

  2. Change in Serum Lipid during Growth Hormone Therapy in a Growth Hormone-Deficient Patient with Decreased Serum Apolipoprotem C-II

    OpenAIRE

    Tadashi, Moriwake; Masanori, Takaiwa; Masako, Kawakami; Shouichi, Tanaka; Tetsuya, Nakamura; Department of Pediatrics, Iwakuni National Hospital; Department of Pediatrics, Iwakuni National Hospital; Department of Pediatrics, Iwakuni National Hospital; Department of Internal Medicine, Iwakuni National Hospital; Department of Radiology, Iwakuni National Hospital

    2003-01-01

    Introduction The effects of GH on lipid metabolism have been discussed frequently in relation to quality of adult life in childhood-onset GH deficiency, but its effects on lipid metabolism were not fully understood. In the present study, we analyzed the longitudinal change in serum lipid metabolites and apolipoproteins in a GH-deficient patient who had a history of cholelithiasis with decreased apolipoprotein C-II. Case K.Y. Four-year old boy visited the emergency clinic of Iwakuni National H...

  3. Pyridoxine deficiency in adult patients with status epilepticus.

    Science.gov (United States)

    Dave, Hina N; Eugene Ramsay, Richard; Khan, Fawad; Sabharwal, Vivek; Irland, Megan

    2015-11-01

    An 8-year-old girl treated at our facility for superrefractory status epilepticus was found to have a low pyridoxine level at 5 μg/L. After starting pyridoxine supplementation, improvement in the EEG for a 24-hour period was seen. We decided to look at the pyridoxine levels in adult patients admitted with status epilepticus. We reviewed the records on patients admitted to the neurological ICU for status epilepticus (SE). Eighty-one adult patients were identified with documented pyridoxine levels. For comparison purposes, we looked at pyridoxine levels in outpatients with epilepsy (n=132). Reported normal pyridoxine range is >10 ng/mL. All but six patients admitted for SE had low normal or undetectable pyridoxine levels. A selective pyridoxine deficiency was seen in 94% of patients with status epilepticus (compared to 39.4% in the outpatients) which leads us to believe that there is a relationship between status epilepticus and pyridoxine levels. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Thyroid peroxidase antibodies during early gestation and the subsequent risk of first-onset postpartum depression: A prospective cohort study.

    Science.gov (United States)

    Wesseloo, Richard; Kamperman, Astrid M; Bergink, Veerle; Pop, Victor J M

    2018-01-01

    During the postpartum period, women are at risk for the new onset of both auto-immune thyroid disorders and depression. The presence of thyroid peroxidase antibodies (TPO-ab) during early gestation is predictive for postpartum auto-immune thyroid dysfunction. The aim of this study was to investigate the association between TPO-ab status during early gestation and first-onset postpartum depression. Prospective cohort study (n = 1075) with follow-up during pregnancy up to one year postpartum. Thyroid function and TPO-ab status were measured during early gestation. Depressive symptomatology was assessed during each trimester and at four time points postpartum with the Edinburgh Depression Scale (EDS). Women with antenatal depression were not eligible for inclusion. Self-reported postpartum depression was defined with an EDS cut-off of ≥ 13. The cumulative incidence of self-reported first-onset depression in the first postpartum year was 6.3%. A positive TPO-ab status was associated with an increased risk for self-reported first-onset depression at four months postpartum (adjusted OR 3.8; 95% CI 1.3-11.6), but not at other postpartum time points. Prevalence rates of self-reported postpartum depression declined after four months postpartum in the TPO-ab positive group, but remained constant in the TPO-ab negative group. Depression was defined with a self-rating questionnaire (EDS). Women with an increased TPO-ab titer during early gestation are at increased risk for self-reported first-onset depression. The longitudinal pattern of self-reported postpartum depression in the TPO-ab positive group was similar to the typical course of postpartum TPO-ab titers changes. This suggests overlap in the etiology of first-onset postpartum depression and auto-immune thyroid dysfunction. Thyroid function should be evaluated in women with first-onset postpartum depression. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Adult-Onset Hypothyroidism Enhances Fear Memory and Upregulates Mineralocorticoid and Glucocorticoid Receptors in the Amygdala

    OpenAIRE

    Montero-Pedrazuela, Ana; Fern?ndez-Lamo, Iv?n; Alieva, Mar?a; Pereda-P?rez, Inmaculada; Venero, C?sar; Guada?o-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 ex...

  6. An iron-deficient diet stimulates the onset of the hepatitis due to hepatic copper deposition in the Long-Evans Cinnamon (LEC) rat

    Energy Technology Data Exchange (ETDEWEB)

    Sugawara, Naoki; Sugawara, Chieko [Sapporo Medical Univ. (Japan). Dept. of Public Health

    1999-09-01

    To study effects of dietary Cu and Fe levels on the onset of hepatitis in Long-Evans Cinnamon (LEC) rats, female rats (40 days old) were fed a semipurified diet containing 0.1 or 10 mg Cu/kg and 1.5 or 150 mg Fe/kg in a 2 x 2 factorial arrangement for 35 days. At 75 days after birth, LEC rats (+Cu-Fe) fed a Cu-sufficient but Fe-deficient diet (Cu, 10 mg/kg; Fe, 1.5 mg/kg) showed jaundice, with lethargy, anorexia, and malaise. The biochemical variables relating to liver function were significantly increased compared to three other groups, a Cu- and Fe-deficient (-Cu-Fe) group, a Cu-deficient but Fe-sufficient (-Cu+Fe) group, and a Cu and Fe sufficient (+Cu+Fe) group. Furthermore, the +Cu-Fe rat liver showed massive necrosis with huge nuclei. The other three groups presented no biochemical and histological findings of hepatitis. Hepatic Cu and metallothionein concentrations were 289 {+-} 87 (mean {+-} SD) {mu}g/g liver and 8.7 {+-} 1.8 mg/g liver, respectively, in the +Cu-Fe rats. However, in the +Cu+Fe group the values were 196 {+-} 28 {mu}g Cu/g liver and 10.8 {+-} 1.0 mg/g liver. Hepatic Fe deposition was not influenced significantly by the dietary Cu level. The +Cu-Fe group with jaundice showed the highest free Cu concentration in the liver among the four groups, but the hepatic free Fe concentration was similar to those in the -Cu+Fe and +Cu+Fe groups. Our results indicate that an Fe-deficient diet enhances the deposition of hepatic Cu due to increased absorption of Cu from the gastrointestinal tract. This deposition stimulated the onset of hepatitis. (orig.)

  7. Generation and characterization of P gene-deficient rabies virus

    International Nuclear Information System (INIS)

    Shoji, Youko; Inoue, Satoshi; Nakamichi, Kazuo; Kurane, Ichiro; Sakai, Takeo; Morimoto, Kinjiro

    2004-01-01

    Rabies virus (RV) deficient in the P gene was generated by reverse genetics from cDNA of HEP-Flury strain lacking the entire P gene. The defective virus was propagated and amplified by rescue of virus, using a cell line that complemented the functions of the deficient gene. The P gene-deficient (def-P) virus replicated its genome and produced progeny viruses in the cell lines that constitutively expressed the P protein, although it grew at a slightly retarded rate compared to the parental strain. In contrast, no progeny virus was produced in the infected host when the def-P virus-infected cells that did not express the P protein. However, we found that the def-P virus had the ability to perform primary transcription (by the virion-associated polymerase) in the infected host without de novo P protein synthesis. The def-P virus was apathogenic in adult and suckling mice, even when inoculated intracranially. Inoculation of def-P virus in mice induced high levels of virus-neutralizing antibody (VNA) and conferred protective immunity against a lethal rabies infection. These results demonstrate the potential utility of gene-deficient virus as a novel live attenuated rabies vaccine

  8. Arthritis is inhibited in Borrelia-primed and infected interleukin-17A-deficient mice after administration of anti-gamma-interferon, anti-tumor necrosis factor alpha and anti-interleukin-6 antibodies.

    Science.gov (United States)

    Kuo, Joseph; Warner, Thomas F; Schell, Ronald F

    2017-08-31

    The role that cytokines play in the induction of Lyme arthritis is gradually being delineated. We showed previously that severe arthritis developed in a T-cell-driven murine model, even in mice lacking interleukin-17A (IL-17A) and administered anti-gamma-interferon (IFN-γ) antibody. Increased levels of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), two pro-inflammatory cytokines, were detected in cultures of popliteal lymph node cells obtained from these mice. We hypothesized that concomitantly administered anti-IL-6, anti-TNF-α and anti-IFN-γ antibodies would inhibit the development of arthritis in IL-17A-deficient mice. Our results showed that swelling of the hind paws and histopathological changes consistent with arthritis were significantly reduced in IL-17A-deficient mice that administered the three anti-cytokine antibodies. These results suggest that treatment with multiple anti-cytokine antibodies can abrogate the induction of Lyme arthritis in mice. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

    Science.gov (United States)

    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

  10. Determination of antibody levels to Candida albicans in healthy and hospitalised adults using a radioimmunoassay

    International Nuclear Information System (INIS)

    Cobb, S.J.; Parratt, D.

    1978-01-01

    A radioimmunoassay for antibody to Candida albicans is described. The test uses whole, killed of organisms as the antigen and radiolabelled sheep anti-human globulins to quantitate different classes of antibody to C. albicans. The assay has been compared with an Ouchterlony precipitin method and found to be simpler, more rapid, and more sensitive than the latter. Results obtained from two groups of symptomless adults indicated that the range of antibody level was wider for a hospitalised group than for a group of blood transfusion donors, particularly in respect of IgG and IgA antibody. The reason for the increase of antibody in hospital patients was not clear but may have been related to antibiotic therapy. The difficulties in interpretation of Candida serology have therefore been re-assessed in the light of more detailed knowledge of the range and type of antibody to be expected in normal individuals. (author)

  11. Seroprevalence of antibodies to diphtheria, tetanus and pertussis among healthy adolescents and adults in Iran.

    Science.gov (United States)

    Pourakbari, Babak; Moradi, Behnaz; Mirzaee, Farin; Mahmoudi, Shima; Teymuri, Mostafa; Mamishi, Setareh

    2013-01-01

    Serologic data on diseases that are preventable by vaccine are useful to evaluate the success of immunization programs. In this study we evaluated the serologic levels of antibodies to diphtheria, tetanus, and pertussis. In a cross sectional study, a total of 360 people aged 10-25 years were randomly selected and classified by sex and age (10-14, 15-20, 21-25 years). Overall, 78.8% of people aged 10-25 years had fully protected levels of diphtheria antibody (> or = 0.1 IU/ML), and 89.7% had fully protected levels of tetanus antibody (> or = 0.1 IU/ML), 94.3% of women aged 15-25 years had anti tetanus antibody sufficient to protect against neonatal tetanus (> or = 0.1 IU/ML). Antibodies to Pertussis toxin (PT) were found in 44.2% samples but only 1.4% had fully protective levels. Antibodies to PT increased with age, ranging from 33.5% in aged 10-14 years to 54.6 % in aged 21-25 years. No differences were found between male and female, except for diphtheria in age group 21-25 years. Results of this study reveal that diphtheria and tetanus (dT) are efficient between booster doses. About pertussis, most people are susceptible to pertussis and increased PT antibodies with age suggest acquired asymptomatic Bordeella pertussis infection. Also B. pertussis infections in adolescents and adults are of concern, as they are the most important source of transmission of pertussis to young, unprotected infants. So one booster dose in adolescents and adults (as CDC recommended), to reduce mortality and morbidity in infants, is therefore suggested.

  12. The onset of depression during the great recession: foreclosure and older adult mental health.

    Science.gov (United States)

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

    2014-03-01

    We examined neighborhood-level foreclosure rates and their association with onset of depressive symptoms in older adults. 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. 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. 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.

  13. Mitogen response of B cells, but not T cells, is impaired in adult vitamin A-deficient rats

    NARCIS (Netherlands)

    van Bennekum, A. M.; Wong Yen Kong, L. R.; Gijbels, M. J.; Tielen, F. J.; Roholl, P. J.; Brouwer, A.; Hendriks, H. F.

    1991-01-01

    The effect of vitamin A deficiency on the mitogen response of splenic B and T lymphocytes was determined in adult vitamin A-deficient rats. Female weanling Brown Norway/Billingham-Rijswijk (BN/BiRij) and Sprague-Dawley rats were fed a semipurified, essentially vitamin A-free diet, which resulted in

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2011-08-01

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

  16. ADA Deficiency: Evaluation of the Clinical and Laboratory Features and the Outcome.

    Science.gov (United States)

    Cagdas, Deniz; Gur Cetinkaya, Pınar; Karaatmaca, Betül; Esenboga, Saliha; Tan, Cagman; Yılmaz, Togay; Gümüş, Ersin; Barış, Safa; Kuşkonmaz, Barış; Ozgur, Tuba Turul; Bali, Pawan; Santisteban, Ines; Orhan, Diclehan; Yüce, Aysel; Cetinkaya, Duygu; Boztug, Kaan; Hershfield, Michael; Sanal, Ozden; Tezcan, İlhan

    2018-05-09

    Adenosine deaminase (ADA) deficiency is an autosomal recessive primary immunodeficiency. It results in the intracellular accumulation of toxic metabolites which have effects particularly on lymphocytes and the brain. The aim of this study was to evaluate the outcome of 13 ADA-deficient patients. We planned to evaluate their clinical and laboratory findings before and after enzyme replacement therapy (ERT), allogeneic hematopoietic stem cell transplantation (aHSCT), and hematopoietic stem cell gene therapy (HSCGT). Measurement of ADA enzyme activity and metabolites and sequencing of the ADA gene were performed in most of the patients with ADA deficiency. One of the patients with late-onset ADA deficiency was diagnosed by the help of primary immunodeficiency panel screening. Ten out of 13 patients were diagnosed as SCID, while 3 out of 13 were diagnosed as delayed-/late-onset ADA deficiency. Late-onset ADA deficiency patients had clinical and laboratory findings of combined immunodeficiency (CID). Eight patients with ADA-SCID were found to have higher levels of ADA metabolite (dAXP%) (62.1% (34.6-71.9)) than 3 patients with delayed-/late-onset ADA deficiency (6.9% (2.1-8.9). All but one patient with SCID had T-B-NK- phenotype, one had T-B-NK+ phenotype. Genetic defect was documented in 11 patients. Four out of 11 patients had compound heterozygous defects. Three out of 4 patients with compound heterozygous defects had delayed-onset/late-onset ADA deficiency. Seven out of 11 patients with SCID had homozygous defects. Five out of 7 had the same homozygous indel frameshift mutation (c.955-959delGAAGA) showing a founder effect. There were two novel splice site defects: one (IVS10+2T>C) was heterozygous in a patient with late-onset ADA deficiency, and the other was homozygous (IVS2delT+2) in a SCID patient. Other defects were missense defects. Nine out of 13 patients were put on pegylated ADA ERT. Four out of six patients were transplanted without using a conditioning

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

    Directory of Open Access Journals (Sweden)

    Rosiello Richard A

    2003-08-01

    Full Text Available Abstract 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

  18. Pica associated with iron deficiency or depletion: clinical and laboratory correlates in 262 non-pregnant adult outpatients

    Directory of Open Access Journals (Sweden)

    Barton James C

    2010-12-01

    Full Text Available Abstract Background There are many descriptions of the association of pica with iron deficiency in adults, but there are few reports in which observations available at diagnosis of iron deficiency were analyzed using multivariable techniques to identify significant predictors of pica. We sought to identify clinical and laboratory correlates of pica in adults with iron deficiency or depletion using univariable and stepwise forward logistic regression analyses. Methods We reviewed charts of 262 non-pregnant adult outpatients (ages ≥18 y who required treatment with intravenous iron dextran. We tabulated their sex, age, race/ethnicity, body mass index, symptoms and causes of iron deficiency or depletion, serum iron and complete blood count measures, and other conditions at diagnosis before intravenous iron dextran was administered. We excluded patients with serum creatinine >133 μmol/L or disorders that could affect erythrocyte or iron measures. Iron deficiency was defined as both SF Results There were 230 women (184 white, 46 black; ages 19-91 y and 32 men (31 white, 1 black; ages 24-81 y. 118 patients (45.0% reported pica; of these, 87.3% reported ice pica (pagophagia. In univariable analyses, patients with pica had lower mean age, black race/ethnicity, and higher prevalences of cardiopulmonary and epithelial manifestations. The prevalence of iron deficiency, with or without anemia, did not differ significantly between patients with and without pica reports. Mean hemoglobin and mean corpuscular volume (MCV were lower and mean red blood cell distribution width (RDW and platelet count were higher in patients with pica. Thrombocytosis occurred only in women and was more prevalent in those with pica (20.4% vs. 8.3%; p = 0.0050. Mean total iron-binding capacity was higher and mean serum ferritin was lower in patients with pica. Nineteen patients developed a second episode of iron deficiency or depletion; concordance of recurrent pica (or absence of

  19. [Voltage-Gated Potassium Channel-Complex Antibodies Associated Encephalopathy and Related Diseases].

    Science.gov (United States)

    Watanabe, Osamu

    2016-09-01

    Voltage-gated potassium channel (VGKC) complex antibodies are auto-antibodies, initially identified in acquired neuromyotonia (aNMT; Isaacs' syndrome), which cause muscle cramps and difficulty in opening the palm of the hands. Subsequently, these antibodies were found in patients presenting with aNMT along with psychosis, insomnia, and dysautonomia, collectively termed Morvan's syndrome (MoS), and in a limbic encephalopathy (LE) patient with prominent amnesia and frequent seizures. Typical LE cases have a distinctive adult-onset, frequent, brief dystonic seizure semiology that predominantly affects the arms and ipsilateral face. It has now been termed faciobrachial dystonic seizures (FBDS). The VGKC complex is a group of proteins that are strongly associated in situ and after extraction in the mild detergent digitonin. Recent studies indicated that the VGKC complex antibodies are mainly directed toward associated proteins (for example LGI1, Caspr2) that complex with VGKCs themselves. Patients with aNMT or MoS are most likely to have Caspr2 antibodies, whereas LGI1 antibodies are found characteristically in patients with FBDS and LE. We systematically identified and quantified autoantibodies in patient sera with VGKC-complex antibody associated encephalopathy and showed the relationship between individual antibodies and patient's symptoms. Furthermore, we revealed how autoantibodies disrupt the physiological functions of target proteins. LGI1 antibodies neutralize the interaction between LGI1 and ADAM22, reducing the synaptic AMPA receptors.

  20. Onset of adult varicella in relation to rural or urban origin and its complications

    International Nuclear Information System (INIS)

    Raza, N.; Zaidi, K.

    2008-01-01

    To determine area of origin of adult varicella patients, whether rural or urban, to compare the mean interval between leaving the area of origin and onset of varicella in adults of rural origin in comparison with those of urban origin and to observe its complications. All patients over the age of 18 years, presenting with acute illness clinically, suggestive of varicella were included in the study. A specially designed proforma was filled for each patient separately, which included demographic features as well as area of origin, whether rural or urban, and the age at which they left the area of origin. These patients were examined, treated and assessed clinically on regular basis for the progress of the disease as well as for its possible local or systemic complications. Data analysis was done by using statistical programme SPSS-10. Out of 9155 adult patients, 156 (1.70%) had varicella, including 128 (82.1%) males and 28 (17.9%) females. Origin was rural in 125 (80.1%) and urban in 31 (19.9%) patients. Mean interval between leaving area of origin and developing varicella in those of rural origin was 01.79+01.78 years and that in patients of urban origin was 03.37+05.72 years (p+0.009). None of the patients developed any complication of the disease. Varicella in adults is generally a benign illness. It is more common among adult males of rural origin and the interval between leaving the area of origin and onset of varicella in these patients is significantly less as compared to that in adults of urban origin. (author)

  1. Living with transversal upper limb reduction deficiency : Limitations experienced by young adults during their transition to adulthood

    NARCIS (Netherlands)

    Lankhorst, Ilse M. F.; Baars, Erwin C. T.; van Wijk, Iris; Janssen, Wim G. M.; Poelma, Margriet J.; van der Sluis, Corry K.

    2017-01-01

    Introduction: During transition to adulthood young adults with disabilities are at risk of experiencing limitations due to changing physical and social requirements. Purpose: To determine whether young adults with transversal upper limb reduction deficiency (tULRD) have experienced limitations in

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

    Science.gov (United States)

    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.

  3. A Historical Cohort Study on the Efficacy of Glucocorticoids and Riboflavin Among Patients with Late-onset Multiple Acyl-CoA Dehydrogenase Deficiency.

    Science.gov (United States)

    Liu, Xin-Yi; Wang, Zhi-Qiang; Wang, Dan-Ni; Lin, Min-Ting; Wang, Ning

    2016-01-20

    Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is the most common type of lipid storage myopathies in China. Most patients with late-onset MADD are well responsive to riboflavin. Up to now, these patients are often treated with glucocorticoids as the first-line drug because they are misdiagnosed as polymyositis without muscle biopsy or gene analysis. Although glucocorticoids seem to improve the fatty acid metabolism of late-onset MADD, the objective evaluation of their rationalization on this disorder and comparison with riboflavin treatment are unknown. We performed a historical cohort study on the efficacy of the two drugs among 45 patients with late-onset MADD, who were divided into glucocorticoids group and riboflavin group. Detailed clinical information of baseline and 1-month follow-up were collected. After 1-month treatment, a dramatic improvement of muscle strength was found in riboflavin group (P riboflavin group (P riboflavin group still presented high-level muscle enzymes and weak muscle strength after 1-month riboflavin treatment, meaning that 1-month treatment duration maybe insufficient and patients should keep on riboflavin supplement for a longer time. Our results provide credible evidences that the overall efficacy of riboflavin is superior to glucocorticoids, and a longer duration of riboflavin treatment is necessary for patients with late-onset MADD.

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

    Science.gov (United States)

    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.

  5. 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.

    Science.gov (United States)

    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 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.

  6. Elevated Troponin Serum Levels in Adult Onset Still’s Disease

    Directory of Open Access Journals (Sweden)

    Carlo Umberto Manzini

    2015-01-01

    Full Text Available Adult onset Still’s disease (AOSD is a rare inflammatory systemic disease that occasionally may affect myocardium. Diagnosis is based on typical AOSD symptoms after the exclusion of well-known infectious, neoplastic, or autoimmune/autoinflammatory disorders. In the case of abrupt, recent onset AOSD, it could be particularly difficult to make the differential diagnosis and in particular to early detect the possible heart involvement. This latter event is suggested by the clinical history of the four patients described here, incidentally observed at our emergency room. All cases were referred because of acute illness (high fever, malaise, polyarthralgias, skin rash, and sore throat, successively classified as AOSD, and they presented abnormally high levels of serum troponin without overt symptoms of cardiac involvement. The timely treatment with steroids (3 cases or ibuprofen (1 case leads to the remission of clinicoserological manifestations within few weeks. These observations suggest that early myocardial injury might be underestimated or entirely overlooked in patients with AOSD; routine cardiac assessment including troponin evaluation should be mandatory in all patients with suspected AOSD.

  7. Delayed Circadian Rhythm in Adults with Attention-Deficit/Hyperactivity Disorder and Chronic Sleep-Onset Insomnia

    NARCIS (Netherlands)

    van Veen, M.M.; Kooij, J.J.S; Boonstra, A. M.; Gordijn, M.C.M.; van Someren, E.J.W.

    2010-01-01

    Background: Previous studies suggest circadian rhythm disturbances in children with attention-deficit/hyperactivity disorder (ADHD) and sleep-onset insomnia (SOI). We investigate here sleep and rhythms in activity and melatonin in adults with ADHD. Methods: Sleep logs and actigraphy data were

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

    OpenAIRE

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

    2008-01-01

    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...

  9. Vitamin D Deficiency and Cardiometabolic Risks: A Juxtaposition of Arab Adolescents and Adults

    OpenAIRE

    Al-Daghri, Nasser M.; Al-Saleh, Yousef; Aljohani, Naji; Alokail, Majed; Al-Attas, Omar; Alnaami, Abdullah M.; Sabico, Shaun; Alsulaimani, Maha; Al-Harbi, Mohammed; Alfawaz, Hanan; Chrousos, George P.

    2015-01-01

    The recent exponential surge in vitamin D research reflects the global epidemic of vitamin D deficiency and its potential impact on several chronic diseases in both children and adults. Several subpopulations, including Arab adolescent boys and girls, remain understudied. This study aims to fill this gap. A total of 2225 apparently healthy Saudi adolescents (1187 boys and 1038 girls, aged 13-17 years old) and 830 adults (368 men and 462 women, aged 18-50 years old) were respectively recruited...

  10. A case of autoimmune epilepsy associated with anti-leucine-rich glioma inactivated subunit 1 antibodies manifesting electrical shock-like sensations and transparent sadness

    Directory of Open Access Journals (Sweden)

    Yoshiko Murata

    2015-01-01

    Full Text Available Autoimmune epilepsy is an isolated phenotype of autoimmune encephalitis, which may be suspected in patients with unexplained adult-onset seizure disorders or resistance to antiepileptic drugs (AEDs. Antibodies against leucine-rich glioma inactivated subunit 1 of the voltage-gated potassium channel (VGKC complex, recently termed anti-LGI-1 antibodies, are one of the causes of autoimmune epilepsies. Bizarre symptoms with extremely short duration and high frequency are clues to the possible presence of autoimmune epilepsy with anti-LGI-1 antibodies. Precise diagnosis is important because autoimmune epilepsy is treatable and the prognosis can be predicted.

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

    Science.gov (United States)

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

    2017-01-01

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

  12. Behavioural Effects of Adult Vitamin D Deficiency in BALB/c Mice Are not Associated with Proliferation or Survival of Neurons in the Adult Hippocampus.

    Directory of Open Access Journals (Sweden)

    Natalie J Groves

    Full Text Available Epidemiological studies have shown that up to one third of adults have insufficient levels of vitamin D and there is an association between low vitamin D concentrations and adverse brain outcomes, such as depression. Vitamin D has been shown to be involved in processes associated with neurogenesis during development. Therefore, the aim of this study was to test the hypothesis that adult vitamin D (AVD deficiency in BALB/c mice was associated with (a adult hippocampal neurogenesis at baseline, b following 6 weeks of voluntary wheel running and (c a depressive-like phenotype on the forced swim test (FST, which may be linked to alterations in hippocampal neurogenesis. We assessed proliferation and survival of adult born hippocampal neurons by counting the number of cells positive for Ki67 and doublecortin (DCX, and incorporation of 5-Bromo-2'-Deoxyuridine (BrdU within newly born mature neurons using immunohistochemistry. There were no significant effects of diet on number of Ki67+, DCX+ or BrdU+ cells in the dentate gyrus. All mice showed significantly increased number of Ki67+ cells and BrdU incorporation, and decreased immobility time in the FST, after voluntary wheel running. A significant correlation was found in control mice between immobility time in the FST and level of hippocampal neurogenesis, however, no such correlation was found for AVD-deficient mice. We conclude that AVD deficiency was not associated with impaired proliferation or survival of adult born neurons in BALB/c mice and that the impact on rodent behaviour may not be due to altered neurogenesis per se, but to altered function of new hippocampal neurons or processes independent of adult neurogenesis.

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

    Science.gov (United States)

    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 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 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.

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

    Science.gov (United States)

    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.

  15. Variation in genes related to cochlear biology is strongly associated with adult-onset deafness in border collies.

    Directory of Open Access Journals (Sweden)

    Jennifer S Yokoyama

    2012-09-01

    Full Text Available 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.

  16. Anti-Transglutaminase 6 Antibodies in Children and Young Adults with Cerebral Palsy

    Directory of Open Access Journals (Sweden)

    Reidun Stenberg

    2014-01-01

    Full Text Available Objectives. We have previously reported a high prevalence of gluten-related serological markers (GRSM in children and young adults with cerebral palsy (CP. The majority had no enteropathy to suggest coeliac disease (CD. Antibodies against transglutaminase 6 (anti-TG6 represent a new marker associated with gluten-related neurological dysfunction. The aim of this study was to investigate the prevalence of anti-TG6 antibodies in this group of individuals with an early neurological injury resulting in CP. Materials and Methods. Sera from 96 patients with CP and 36 controls were analysed for IgA/IgG class anti-TG6 by ELISA. Results. Anti-TG6 antibodies were found in 12/96 (13% of patients with CP compared to 2/36 (6% in controls. The tetraplegic subgroup of CP had a significantly higher prevalence of anti-TG6 antibodies 6/17 (35% compared to the other subgroups and controls. There was no correlation of anti-TG6 autoantibodies with seropositivity to food proteins including gliadin. Conclusions. An early brain insult and associated inflammation may predispose to future development of TG6 autoimmunity.

  17. Late-Onset Glycogen Storage Disease Type II (Pompe's Disease) with a Novel Mutation: A Malaysian Experience.

    Science.gov (United States)

    Fu Liong, Hiew; Abdul Wahab, Siti Aishah; Yakob, Yusnita; Lock Hock, Ngu; Thong, Wong Kum; Viswanathan, Shanthi

    2014-01-01

    Pompe's disease (acid maltase deficiency, glycogen storage disease type II) is an autosomal recessive disorder caused by a deficiency of lysosomal acid α-1,4-glucosidase, resulting in excessive accumulation of glycogen in the lysosomes and cytoplasm of all tissues, most notably in skeletal muscles. We present a case of adult-onset Pompe's disease with progressive proximal muscles weakness over 5 years and respiratory failure on admission, requiring prolonged mechanical ventilation. Electromyography showed evidence of myopathic process with small amplitudes, polyphasic motor unit action potentials, and presence of pseudomyotonic discharges. Muscle biopsy showed glycogen-containing vacuoles in the muscle fibers consistent with glycogen storage disease. Genetic analysis revealed two compound heterozygous mutations at c.444C>G (p.Tyr148∗) in exon 2 and c.2238G>C (p.Trp746Cys) in exon 16, with the former being a novel mutation. This mutation has not been reported before, to our knowledge. The patient was treated with high protein diet during the admission and subsequently showed good clinical response to enzyme replacement therapy with survival now to the eighth year. Conclusion. In patients with late-onset adult Pompe's disease, careful evaluation and early identification of the disease and its treatment with high protein diet and enzyme replacement therapy improve muscle function and have beneficial impact on long term survival.

  18. Changes of grey matter volume in first-episode drug-naive adult major depressive disorder patients with different age-onset

    Directory of Open Access Journals (Sweden)

    Zonglin Shen

    2016-01-01

    Conclusions: The GMV of the brain areas that were related to mood regulation was decreased in the first-episode, drug-naive adult patients with MDD. Adult patients with EOD and LOD exhibited different GMV changes relative to each age-matched comparison group, suggesting depressed adult patients with different age-onset might have different pathological mechanism.

  19. Determinants of Social Outcomes in Adults With Childhood-onset Epilepsy

    Science.gov (United States)

    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

  20. Urea Cycle Defects: Early-Onset Disease Associated with A208T Mutation in OTC Gene-Expanding the Clinical Phenotype.

    Science.gov (United States)

    Sánchez, Ana Isabel; Rincón, Alejandra; García, Mary; Suárez-Obando, Fernando

    2017-01-01

    Ornithine transcarbamylase deficiency (OMIM: 311250) is the most common disorder of urea cycle disorders, accounting for nearly 50% of all cases. We report a case of a two-month- old male patient, who attends our medical genetics consultation because of low citrulline levels and elevated glutamine to citrulline ratio detected by expanded newborn screening with tandem mass spectrometry. He is an asymptomatic male with a normal physical examination and appropriate neurodevelopmental milestones. The patient has a family history of one older brother who died at 18 months old from severe and sudden hyperammonemia and a maternal aunt who suddenly died at two years old. He had high plasma ammonium concentration and a confirmed OTC mutation (p.A208T). Usually, this mutation causes OTC deficiency of late onset in adult males. However, this report raises awareness about mutations previously described as a late-onset causing disease, which can cause severe hyperammonemia and high risk of dying at an early age.

  1. Urea Cycle Defects: Early-Onset Disease Associated with A208T Mutation in OTC Gene—Expanding the Clinical Phenotype

    Directory of Open Access Journals (Sweden)

    Ana Isabel Sánchez

    2017-01-01

    Full Text Available Ornithine transcarbamylase deficiency (OMIM: 311250 is the most common disorder of urea cycle disorders, accounting for nearly 50% of all cases. We report a case of a two-month- old male patient, who attends our medical genetics consultation because of low citrulline levels and elevated glutamine to citrulline ratio detected by expanded newborn screening with tandem mass spectrometry. He is an asymptomatic male with a normal physical examination and appropriate neurodevelopmental milestones. The patient has a family history of one older brother who died at 18 months old from severe and sudden hyperammonemia and a maternal aunt who suddenly died at two years old. He had high plasma ammonium concentration and a confirmed OTC mutation (p.A208T. Usually, this mutation causes OTC deficiency of late onset in adult males. However, this report raises awareness about mutations previously described as a late-onset causing disease, which can cause severe hyperammonemia and high risk of dying at an early age.

  2. Increased serum and bone matrix levels of transforming growth factor {beta}1 in patients with GH deficiency in response to GH treatment

    DEFF Research Database (Denmark)

    Ueland, Thor; Lekva, Tove; Otterdal, Kari

    2011-01-01

    Patients with adult onset GH deficiency (aoGHD) have secondary osteoporosis, which is reversed by long-term GH substitution. Transforming growth factor β1 (TGFβ1 or TGFB1) is abundant in bone tissue and could mediate some effects of GH/IGFs on bone. We investigated its regulation by GH/IGF1 in vivo...

  3. The impact of adult vitamin D deficiency on behaviour and brain function in male Sprague-Dawley rats.

    Directory of Open Access Journals (Sweden)

    Jacqueline H Byrne

    Full Text Available BACKGROUND: Vitamin D deficiency is common in the adult population, and this has been linked to depression and cognitive outcomes in clinical populations. The aim of this study was to investigate the effects of adult vitamin D (AVD deficiency on behavioural tasks of relevance to neuropsychiatric disorders in male Sprague-Dawley rats. METHODS: Ten-week old male Sprague-Dawley rats were fed a control or vitamin D deficient diet for 6 weeks prior to, and during behavioural testing. We first examined a range of behavioural domains including locomotion, exploration, anxiety, social behaviour, learned helplessness, sensorimotor gating, and nociception. We then assessed locomotor response to the psychomimetic drugs, amphetamine and MK-801. Attention and vigilance were assessed using the 5 choice serial reaction time task (5C-SRT and the 5 choice continuous performance task (5C-CPT and, in a separate cohort, working memory was assessed using the delay match to sample (DMTS task. We also examined excitatory and inhibitory neurotransmitters in prefrontal cortex and striatum. RESULTS: AVD-deficient rats were deficient in vitamin D3 (<10 nM and had normal calcium and phosphate levels after 8-10 weeks on the diet. Overall, AVD deficiency was not associated with an altered phenotype across the range of behavioural domains tested. On the 5C-SRT AVD-deficient rats made more premature responses and more head entries during longer inter-trial intervals (ITI than control rats. On the 5C-CPT AVD-deficient rats took longer to make false alarm (FA responses than control rats. AVD-deficient rats had increases in baseline GABA levels and the ratio of DOPAC/HVA within the striatum. CONCLUSIONS: AVD-deficient rats exhibited no major impairments in any of the behavioural domains tested. Impairments in premature responses in AVD-deficient rats may indicate that these animals have specific alterations in striatal systems governing compulsive or reward-seeking behaviour.

  4. Respiratory infections in adults with atopic disease and IgE antibodies to common aeroallergens.

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    Aino Rantala

    Full Text Available BACKGROUND: Atopic diseases, including allergic rhinitis, allergic dermatitis and asthma, are common diseases with a prevalence of 30-40% worldwide and are thus of great global public health importance. Allergic inflammation may influence the immunity against infections, so atopic individuals could be susceptible to respiratory infections. No previous population-based study has addressed the relation between atopy and respiratory infections in adulthood. We assessed the relation between atopic disease, specific IgE antibodies and the occurrence of upper and lower respiratory infections in the past 12 months among working-aged adults. METHODS AND FINDINGS: A population-based cross-sectional study of 1008 atopic and non-atopic adults 21-63 years old was conducted. Information on atopic diseases, allergy tests and respiratory infections was collected by a questionnaire. Specific IgE antibodies to common aeroallergens were measured in serum. Adults with atopic disease had a significantly increased risk of lower respiratory tract infections (LRTI; including acute bronchitis and pneumonia with an adjusted risk ratio (RR 2.24 (95% confidence interval [CI] 1.43, 3.52 and upper respiratory tract infections (URTI; including common cold, sinusitis, tonsillitis, and otitis media with an adjusted RR 1.55 (1.14, 2.10. The risk of LRTIs increased with increasing level of specific IgE (linear trend P = 0.059. CONCLUSIONS: This study provides new evidence that working-aged adults with atopic disease experience significantly more LRTIs and URTIs than non-atopics. The occurrence of respiratory infections increased with increasing levels of specific IgE antibodies to common aeroallergens, showing a dose-response pattern with LRTIs. From the clinical point of view it is important to recognize that those with atopies are a risk group for respiratory infections, including more severe LRTIs.

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

    Science.gov (United States)

    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…

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

    Science.gov (United States)

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

    2014-08-01

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

  7. DCLRE1C (ARTEMIS) mutations causing phenotypes ranging from atypical severe combined immunodeficiency to mere antibody deficiency.

    Science.gov (United States)

    Volk, Timo; Pannicke, Ulrich; Reisli, Ismail; Bulashevska, Alla; Ritter, Julia; Björkman, Andrea; Schäffer, Alejandro A; Fliegauf, Manfred; Sayar, Esra H; Salzer, Ulrich; Fisch, Paul; Pfeifer, Dietmar; Di Virgilio, Michela; Cao, Hongzhi; Yang, Fang; Zimmermann, Karin; Keles, Sevgi; Caliskaner, Zafer; Güner, S Ükrü; Schindler, Detlev; Hammarström, Lennart; Rizzi, Marta; Hummel, Michael; Pan-Hammarström, Qiang; Schwarz, Klaus; Grimbacher, Bodo

    2015-12-20

    Null mutations in genes involved in V(D)J recombination cause a block in B- and T-cell development, clinically presenting as severe combined immunodeficiency (SCID). Hypomorphic mutations in the non-homologous end-joining gene DCLRE1C (encoding ARTEMIS) have been described to cause atypical SCID, Omenn syndrome, Hyper IgM syndrome and inflammatory bowel disease-all with severely impaired T-cell immunity. By whole-exome sequencing, we investigated the molecular defect in a consanguineous family with three children clinically diagnosed with antibody deficiency. We identified perfectly segregating homozygous variants in DCLRE1C in three index patients with recurrent respiratory tract infections, very low B-cell numbers and serum IgA levels. In patients, decreased colony survival after irradiation, impaired proliferative response and reduced counts of naïve T cells were observed in addition to a restricted T-cell receptor repertoire, increased palindromic nucleotides in the complementarity determining regions 3 and long stretches of microhomology at switch junctions. Defective V(D)J recombination was complemented by wild-type ARTEMIS protein in vitro. Subsequently, homozygous or compound heterozygous DCLRE1C mutations were identified in nine patients from the same geographic region. We demonstrate that DCLRE1C mutations can cause a phenotype presenting as only antibody deficiency. This novel association broadens the clinical spectrum associated with ARTEMIS mutations. Clinicians should consider the possibility that an immunodeficiency with a clinically mild initial presentation could be a combined immunodeficiency, so as to provide appropriate care for affected patients. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

    Science.gov (United States)

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

    2011-11-01

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

  9. [Vaccination against viral hepatitis A and B in adults aged over 40 years--antibody persistence and immune memory].

    Science.gov (United States)

    Chlibek, R; Smetana, J; Bostíková, V; Splino, M

    2011-09-01

    Primary vaccination with combined vaccine against viral hepatitis A (VHA) and viral hepatitis B (VHB) induces higher anti-hepatitis B surface (anti-HBs) antibody responses and similar anti-hepatitis A virus (anti-HAV) antibody responses in adults aged over 40 years in comparison with concomitant monovalent vaccines against VHA and VHB. Th e objectives were to assess, in a clinical study, persistence of anti-HAV and anti-HBs antibodies in adults aged over 40 years four years after primary VHA/VHB vaccination and antibody response following a booster dose of the vaccine. Five hundred and ninety-six subjects aged > 40 years were vaccinated with three doses of the combined VHA/VHB vaccine at Months 0, 1, 6 (HAB group) or with concomitant VHA and VHB vaccines at Months 0, 6 and 0, 1, 6 (ENG+HAV and HBVX+VAQ, respectively). Blood samples were collected one month following primary vaccination (Month 7) and then at one-year intervals for four years after the booster dose with the same vaccine as used for the primary vaccination. The anti-HBs and anti-HAV antibody levels were determined prior to the booster dose and at days 14 and 30 after the booster dose. At Month 7, > 97% of study subjects were seropositive for anti-HAV antibodies in all groups analyzed. Four years after primary vaccination, anti-HAV antibody seropositivity persisted in > 93% of study subjects, increasing to > 99% after the booster dose. At Month 7, the highest proportion of study subjects with anti-HBs antibody levels > or = 10 mIU/ml was found in the HAB group (91.7% versus 79.7% in the ENG+HAV group versus 71.0% in the HBVX+VAQ group). Four years after vaccination, anti-HBs antibody levels of 10 mIU/ml persisted in 57.1% of the HAB study subjects in comparison with 40.1% and 26.6% of the study subjects in the ENG+HAV and HBVX+VAQ groups, respectively. One month after the booster dose, anti-HBs antibody levels increased and antibody levels > or = 10 mIU/ml was achived in 95.2% of study subjects in the

  10. Adult hypopituitarism: Are we missing or is it clinical lethargy?

    Directory of Open Access Journals (Sweden)

    K S Brar

    2011-01-01

    Full Text Available Hypopituitarism, a disease of varied etiologies, is a serious endocrine illness that requires early recognition and prompt treatment to avoid its severe deleterious effects. In adults it is often missed due to non-specific symptoms of growth hormone deficiency and hypogonadism or mild deficiencies of other pituitary hormones. In some it may present with acute onset of symptoms suggestive of acute adrenal (corticotropin insufficiency or symptoms due to mass lesion in/or around pituitary. High index of suspicion is required to seek hypopituitarism in patients with non-specific symptoms such as fatigue and malaise. Treatment of isolated hormone deficiency, partial or panhypopituitarism, has gratifying results although they require lifelong treatment and follow-up.

  11. Late-onset hypogonadism

    Directory of Open Access Journals (Sweden)

    Piotr Dudek

    2017-06-01

    Full Text Available In Poland, the number of men over the age of 50 years exceeds 6 million. It is estimated that about 2-6% of this population develops symptoms of late-onset hypogonadism (LOH. In men, testosterone deficiency increases slightly with age. LOH is a clinically and biochemically defined disease of older men with serum testosterone level below the reference parameters of younger healthy men and with symptoms of testosterone deficiency, manifested by pronounced disturbances of quality of life and harmful effects on multiple organ systems. Testosterone replacement therapy may give several benefits regarding body composition, metabolic control, and psychological and sexual parameters.

  12. Infantile Onset Myasthenia Gravis with MuSK Antibodies

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2006-08-01

    Full Text Available A late infantile case of myasthenia gravis (MG with anti-muscle-specific receptor tyrosine kinase (MuSK high antibody (Ab titer is reported from Kyushu University, Fukuoka; and Nagasaki University, Japan.

  13. Late-onset 3 beta-hydroxysteroid dehydrogenase deficiency with virilization induced by a large ovarian cyst.

    Science.gov (United States)

    Heinrich, U; Eberlein-Gonska, M; Benz, G; Haack, D; Otto, H F

    1993-01-01

    A midpubertal girl presented with secondary amenorrhea and a rapidly progressive deepening of her voice as the only signs of virilization. Diagnostic work-up yielded an extremely elevated plasma testosterone (289 ng/dl), low estradiol (29 pg/ml) levels and a large solitary cyst of the right ovary, which was totally removed. Pathohistology was in keeping with a granulosa cyst with mild luteinization. Normalization of testosterone (to 27.3 ng/dl) and estradiol (to 62 pg/ml) and resumption of regular menses after 2 months clearly indicated an autonomous function of the cyst. A malignant tumor was unequivocally excluded. Basal and ACTH stimulated levels of adrenal androgens pointed to a late-onset 3 beta-hydroxysteroid dehydrogenase deficiency, which per se is known to induce polycystic ovarian changes, but to date has never been described to be accompanied with a large and autonomous follicular cyst.

  14. Poor Heart Rate Recovery Is Associated With the Development of New-Onset Atrial Fibrillation in Middle-Aged Adults.

    Science.gov (United States)

    Sabbag, Avi; Berkovitch, Anat; Sidi, Yechezkel; Kivity, Shaye; Ben Zekry, Sagit; Beinart, Roy; Segev, Shlomo; Glikson, Michael; Goldenberg, Ilan; Maor, Elad

    2016-12-01

    To investigate the association between heart rate recovery (HRR) and new-onset atrial fibrillation (AF) in middle-aged adults. Heart rate recovery was calculated using the exercise stress test in 15,729 apparently healthy self-referred men and women who attended periodic health screening examinations between January 2000, and December 2015. All participants completed the maximal exercise stress test according to the Bruce protocol and were followed clinically on a yearly basis for a median of 6.4±4 years. The primary end point was new-onset AF. Participants were grouped according to HRR at 5 minutes, dichotomized at the median value (age, male sex, obesity resting heart rate, and ischemic heart disease were all associated with increased AF risk in a univariate Cox regression model (Pnew-onset AF during long-term follow-up in middle-aged adults. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  15. HIV Antibody Testing among Adults in the United States: Data from 1988 NHIS.

    Science.gov (United States)

    Hardy, Ann M.; Dawson, Deborah A.

    1990-01-01

    Analyzes statistical data from 1988 National Health Interview Survey to determine adult awareness of and experience with HIV antibody testing. Following findings reported: most knew of test; 17 percent had been tested; Blacks and Hispanics were more likely than Whites to have been voluntarily tested; and high-risk group members were more likely…

  16. Late-Onset Glycogen Storage Disease Type II (Pompe’s Disease with a Novel Mutation: A Malaysian Experience

    Directory of Open Access Journals (Sweden)

    Hiew Fu Liong

    2014-01-01

    Full Text Available Pompe’s disease (acid maltase deficiency, glycogen storage disease type II is an autosomal recessive disorder caused by a deficiency of lysosomal acid α-1,4-glucosidase, resulting in excessive accumulation of glycogen in the lysosomes and cytoplasm of all tissues, most notably in skeletal muscles. We present a case of adult-onset Pompe’s disease with progressive proximal muscles weakness over 5 years and respiratory failure on admission, requiring prolonged mechanical ventilation. Electromyography showed evidence of myopathic process with small amplitudes, polyphasic motor unit action potentials, and presence of pseudomyotonic discharges. Muscle biopsy showed glycogen-containing vacuoles in the muscle fibers consistent with glycogen storage disease. Genetic analysis revealed two compound heterozygous mutations at c.444C>G (p.Tyr148* in exon 2 and c.2238G>C (p.Trp746Cys in exon 16, with the former being a novel mutation. This mutation has not been reported before, to our knowledge. The patient was treated with high protein diet during the admission and subsequently showed good clinical response to enzyme replacement therapy with survival now to the eighth year. Conclusion. In patients with late-onset adult Pompe’s disease, careful evaluation and early identification of the disease and its treatment with high protein diet and enzyme replacement therapy improve muscle function and have beneficial impact on long term survival.

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

    Science.gov (United States)

    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

  18. Dose dependency of time of onset of radiation-induced growth hormone deficiency

    International Nuclear Information System (INIS)

    Clayton, P.E.; Shalet, S.M.

    1991-01-01

    Growth hormone (GH) secretion during insulin-induced hypoglycemia was assessed on 133 occasions in 82 survivors of childhood malignant disease. All had received cranial irradiation with a dose range to the hypothalamic-pituitary axis of 27 to 47.5 Gy (estimated by a schedule of 16 fractions over 3 weeks) and had been tested on one or more occasions between 0.2 and 18.9 years after treatment. Results of one third of the GH tests were defined as normal (GH peak response, greater than 15 mU/L) within the first 5 years, in comparison with 16% after 5 years. Stepwise multiple linear regression analysis showed that dose (p = 0.007) and time from irradiation (p = 0.03), but not age at therapy, had a significant influence on peak GH responses. The late incidence of GH deficiency was similar over the whole dose range (4 of 26 GH test results normal for less than 30 Gy and 4 of 25 normal for greater than or equal to 30 Gy after 5 years), but the speed of onset over the first years was dependent on dose. We conclude that the requirement for GH replacement therapy and the timing of its introduction will be influenced by the dose of irradiation received by the hypothalamic-pituitary axis

  19. [EFFICACY OF IVIG TREATMENT IN BRONCHIECTASIS ASSOCIATED WITH IGG SUBCLASS DEFICIENCY].

    Science.gov (United States)

    Shostak, Yael; Kramer, Mordechai R

    2017-11-01

    Bronchiectasis is characterized by an abnormal dilatation of the bronchi leading to a chronic inflammatory process, airway blockage and impaired clearance of secretions. The damage to the airways is usually progressive and is the result of several pathogenic processes. In the past, healing of infections (especially pulmonary tuberculosis) was the main cause of airway dilatation and progression of chronic inflammation. Today, congenital illnesses, anatomical defects and immune deficiency play an important role in the pathogenesis of bronchiectasis formation. The immunoglobulin repertoire is vital for effective host protection against a wide variety of pathogens. Primary antibody deficiency diseases are defects of the humoral arm of the immune system and involve an absence/reduced levels of one or more immunoglobulin classes/subclasses or defects of specific antibody formation. Immunoglobulin G (IGG) subclass deficiency can occur in a healthy person and could be without clinical significance. However, in recent years there is emerging evidence that in patients with recurrent infections, early diagnosis of antibody deficiency affects the prognosis and prevention of ongoing lung damage. The use of IVIG has contributed significantly to the survival rate in primary antibody deficiencies. There is limited literature on the treatment of IVIG for patients with IGG subclass deficiency. However, all studies presented so far demonstrated that immunoglobulin therapy reduced the rate of bacterial infections, days of antibiotic usage, hospital admissions and significantly increased patients' quality of life. Therefore, in the appropriate clinical setting, ie: a patient with bronchiectasis and recurrent infections, it is justified to test whether there are humoral immune defects such as IGG subclass deficiency. In a patient with proven deficiency, we should recommend to start IVIG treatment until clinical benefit is achieved.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Jie Zhang

    2015-06-01

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

  2. Antibody response to booster vaccination with tetanus and diphtheria in adults exposed to perfluorinated alkylates.

    Science.gov (United States)

    Kielsen, Katrine; Shamim, Zaiba; Ryder, Lars P; Nielsen, Flemming; Grandjean, Philippe; Budtz-Jørgensen, Esben; Heilmann, Carsten

    2016-01-01

    Recent studies suggest that exposure to perfluorinated alkylate substances (PFASs) may induce immunosuppression in humans and animal models. In this exploratory study, 12 healthy adult volunteers were recruited. With each subject, serum-PFAS concentrations were measured and their antibody responses prospectively followed for 30 days after a booster vaccination with diphtheria and tetanus. The results indicated that serum-PFAS concentrations were positively correlated and positively associated with age and male sex. The specific antibody concentrations in serum were increased from Day 4 to Day 10 post-booster, after which a constant concentration was reached. Serum PFAS concentrations showed significant negative associations with the rate of increase in the antibody responses. Interestingly, this effect was particularly strong for the longer-chain PFASs. All significant associations remained significant after adjustment for sex and age. Although the study involved a small number of subjects, these findings of a PFAS-associated reduction of the early humoral immune response to booster vaccination in healthy adults supported previous findings of PFAS immunosuppression in larger cohorts. Furthermore, the results suggested that cellular mechanisms right after antigen exposure should be investigated more closely to identify possible mechanisms of immunosuppression from PFAS.

  3. HASHIMOTO THYROIDITIS NOT ASSOCIATED WITH VITAMIN D DEFICIENCY.

    Science.gov (United States)

    Yasmeh, Joseph; Farpour, Farzin; Rizzo, Vincent; Kheradnam, Sharon; Sachmechi, Issac

    2016-07-01

    Vitamin D deficiency is associated with several autoimmune diseases. This study assessed whether vitamin D deficiency is associated with Hashimoto thyroiditis (HT). Two groups of patients were selected for which serum 25-hydroxyvitamin D (25(OH)D) levels had been measured: (1) a study group of patients diagnosed with HT as indicated by thyroid antibodies, and (2) a healthy control group. Each group was separated by sex and then controlled for age and body mass index (BMI). Groups' mean 25(OH)D levels were compared by analysis of variance (ANOVA), and percent frequencies of vitamin D sufficiency, insufficiency, and deficiency were compared with a Z-test. The correlations between 25(OH)D levels and thyroid antibodies and thyroid-stimulating hormone (TSH) levels were also tested. The mean 25(OH)D levels for the HT and control groups were significantly different in females (30.75 vs. 27.56 ng/mL, respectively) but not in males (14.24 vs. 13.26 ng/mL). HT females had a higher rate of vitamin D sufficiency (51.7% vs. 31.1%) and a lower rate of insufficiency (48.3% vs. 68.9%) relative to control females. No such differences were found in the male groups. None of the females were vitamin D deficient, but almost all males were. A significant (P = .016) positive correlation (rs = 0.436) between 25(OH)D and TPOAb was observed in males. HT is not associated with higher rates of vitamin D deficiency relative to a control group. BMI = body mass index HT = Hashimoto thyroiditis 25(OH)D = 25-hydroxyvitamin D TgAb = thyroglobulin antibody TSH = thyroid-stimulating hormone TPOAb = thyroid-peroxidase antibody VDR = Vitamin D receptor.

  4. Antibodies to biotinylated red blood cells in adults and infants: improved detection, partial characterization, and dependence on red blood cell-biotin dose.

    Science.gov (United States)

    Schmidt, Robert L; Mock, Donald M; Franco, Robert S; Cohen, Robert M; North, Anne K; Cancelas, José A; Geisen, Christof; Strauss, Ronald G; Vlaar, Alexander P; Nalbant, Demet; Widness, John A

    2017-06-01

    Biotin-labeled red blood cells (BioRBCs) are used for in vivo kinetic studies. Because BioRBC dosing occasionally induces antibodies, a sensitive and specific anti-BioRBC detection assay is needed. Aims were to 1) develop a gel card assay to evaluate existing, naturally occurring and BioRBC-induced plasma antibodies, 2) compare gel card and tube agglutination detection results, and 3) test for a relationship of antibody induction and BioRBC dose. Reagent BioRBCs were prepared using sulfo-NHS biotin ranging from densities 18 (BioRBC-18) to 1458 (BioRBC-1458) µg/mL RBCs. Among BioRBC-exposed subjects, gel card and tube agglutination results were concordant in 21 of 22 adults and all 19 infant plasma samples. Gel card antibody detection sensitivity was more than 10-fold greater than tube agglutination. Twelve to 16 weeks after BioRBC exposure, induced anti-antibodies were detected by gel card in three of 26 adults (12%) at reagent densities BioRBC-256 or less, but in none of 41 infants. Importantly, induced anti-BioRBC antibodies were associated with higher BioRBC dose (p = 0.008); no antibodies were detected in 18 subjects who received BioRBC doses less than or equal to BioRBC-18. For noninduced BioRBC antibodies, six of 1125 naïve adults (0.3%) and none of 46 naïve infants demonstrated existing anti-BioRBC antibodies using reagent BioRBC-140 or -162. Existing anti-BioRBCs were all neutralized by biotin compounds, while induced antibodies were not. The gel card assay is more sensitive than the tube agglutination assay. We recommend reagent BioRBC-256 for identifying anti-BioRBCs. Use of a low total RBC biotin label dose (≤ BioRBC-18) may minimize antibody induction. © 2017 AABB.

  5. [Current Perspective on Voltage-gated Potassium Channel Complex Antibody Associated Diseases].

    Science.gov (United States)

    Watanabe, Osamu

    2018-04-01

    Voltage-gated potassium channel (VGKC) complex auto-antibodies were initially identified in Isaacs' syndrome (IS), which is characterized by muscle cramps and neuromyotonia. These antibodies were subsequently identified in patients with Morvan's syndrome (MoS), which includes IS in conjunction with psychosis, insomnia, and dysautonomia. The antibodies have also been detected in a patient with limbic encephalopathy (LE) presenting with prominent amnesia and frequent seizures. Typical cases of LE have adult-onset, with frequent, brief dystonic seizures that predominantly affect the arms and ipsilateral face, and has recently been termed faciobrachial dystonic seizures. Autoantibodies against the extracellular domains of VGKC complex proteins, leucine-rich glioma-inactivated 1 (LGI1), and contactin-associated protein-2 (Caspr2), occur in patients with IS, MoS, and LE. However, routine testing has detected VGKC complex antibodies without LGI1 or Caspr2 reactivities (double-negative) in patients with other diseases, such as Creutzfeldt-Jakob disease and amyotrophic lateral sclerosis. Furthermore, double-negative VGKC complex antibodies are often directed against cytosolic epitopes of Kv1 subunits. Therefore, these antibodies should no longer be classified as neuronal-surface antibodies and lacking pathogenic potential. Novel information has been generated regarding autoantibody disruption of the physiological functions of target proteins. LGI1 antibodies neutralize the interaction between LGI1 and ADAM22, thereby reducing the synaptic AMPA receptors. It may be that the main action is on inhibitory neurons, explaining why the loss of AMPA receptors causes amnesia, neuronal excitability and seizures.

  6. Genetics Home Reference: lysosomal acid lipase deficiency

    Science.gov (United States)

    ... lipase deficiency develop multi-organ failure and severe malnutrition and generally do not survive past 1 year. In the later-onset form of lysosomal acid lipase deficiency , signs and symptoms vary and usually begin in mid-childhood, although they can appear anytime up to late ...

  7. Immunity to endotoxin and Asp299Gly polymorphism of TLR-4 in adult patients with early and late onset of asthma

    Directory of Open Access Journals (Sweden)

    Yu. A. Bisyuk

    2015-06-01

    Full Text Available Aim. The gene polymorphism of Asp299Gly TLR-4 may be associated with the risk of asthma development. Methods and results. The gene polymorphism of TLR-4 (Asp299Gly receptor has been researched in 262 early-onset and in 69 late-onset asthma patients. The state of anti-endotoxin immunity was assessed by determination of specific antibodies to the endotoxin of A, M, G classes and sCD14 by ELISA. The polymorphism was analyzed by the allele-specific polymerase chain reaction with electrophoretic detection. It was estimated that the risk of early-onset asthma in the population of Crimea is associated with genotypes AG and GG (Asp299Gly of TLR-4. There were increased levels of anti-endotoxin IgM and decreased of sIgA in patients with late-onset asthma and AA genotype as compared to other genotypes. Conclusion. The gene polymorphism of Asp299Gly TLR-4 is associated with the risk of early-onset asthma development in Crimea population.

  8. Anti-MOG antibody-positive ADEM following infectious mononucleosis due to a primary EBV infection: a case report.

    Science.gov (United States)

    Nakamura, Yoshitsugu; Nakajima, Hideto; Tani, Hiroki; Hosokawa, Takafumi; Ishida, Shimon; Kimura, Fumiharu; Kaneko, Kimihiko; Takahashi, Toshiyuki; Nakashima, Ichiro

    2017-04-19

    Anti-Myelin oligodendrocyte glycoprotein (MOG) antibodies are detected in various demyelinating diseases, such as pediatric acute disseminated encephalomyelitis (ADEM), recurrent optic neuritis, and aquaporin-4 antibody-seronegative neuromyelitis optica spectrum disorder. We present a patient who developed anti-MOG antibody-positive ADEM following infectious mononucleosis (IM) due to Epstein-Barr virus (EBV) infection. A 36-year-old healthy man developed paresthesia of bilateral lower extremities and urinary retention 8 days after the onset of IM due to primary EBV infection. The MRI revealed the lesions in the cervical spinal cord, the conus medullaris, and the internal capsule. An examination of the cerebrospinal fluid revealed pleocytosis. Cell-based immunoassays revealed positivity for anti-MOG antibody with a titer of 1:1024 and negativity for anti-aquaporin-4 antibody. His symptoms quickly improved after steroid pulse therapy followed by oral betamethasone. Anti-MOG antibody titer at the 6-month follow-up was negative. This case suggests that primary EBV infection would trigger anti-MOG antibody-positive ADEM. Adult ADEM patients can be positive for anti-MOG antibody, the titers of which correlate well with the neurological symptoms.

  9. Antibody response to booster vaccination with tetanus and diphtheria in adults exposed to perfluorinated alkylates

    DEFF Research Database (Denmark)

    Kielsen, Katrine; Shamim, Zaiba; Ryder, Lars P.

    2016-01-01

    Recent studies suggest that exposure to perfluorinated alkylate substances (PFASs) may induce immunosuppression in humans and animal models. In this exploratory study, 12 healthy adult volunteers were recruited. With each subject, serum-PFAS concentrations were measured and their antibody responses...... prospectively followed for 30 days after a booster vaccination with diphtheria and tetanus. The results indicated that serum-PFAS concentrations were positively correlated and positively associated with age and male sex. The specific antibody concentrations in serum were increased from Day 4 to Day 10 post......-booster, after which a constant concentration was reached. Serum PFAS concentrations showed significant negative associations with the rate of increase in the antibody responses. Interestingly, this effect was particularly strong for the longer-chain PFASs. All significant associations remained significant after...

  10. Deficient plasticity in the hippocampus and the spiral of addiction: focus on adult neurogenesis.

    Science.gov (United States)

    Canales, Juan J

    2013-01-01

    Addiction is a complex neuropsychiatric disorder which causes disruption at multiple levels, including cognitive, emotional, and behavioral domains. Traditional biological theories of addiction have focused on the mesolimbic dopamine pathway and the nucleus accumbens as anatomical substrates mediating addictive-like behaviors. More recently, we have begun to recognize the engagement and dynamic influence of a much broader circuitry which encompasses the frontal cortex, the amygdala, and the hippocampus. In particular, neurogenesis in the adult hippocampus has become a major focus of attention due to its ability to influence memory, motivation, and affect, all of which are disrupted in addiction. First, I summarize toxicological data that reveal strongly suppressive effects of drug exposure on adult hippocampal neurogenesis. Then, I discuss the impact of deficient neurogenesis on learning and memory function, stress responsiveness and affective behavior, as they relate to addiction. Finally, I examine recent behavioral observations that implicate neurogenesis in the adult hippocampus in the emergence and maintenance of addictive behavior. The evidence reviewed here suggests that deficient neurogenesis is associated with several components of the downward spiraling loop that characterizes addiction, including elevated sensitivity to drug-induced reward and reinforcement, enhanced neurohormonal responsiveness, emergence of a negative affective state, memory impairment, and inflexible behavior.

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

    Science.gov (United States)

    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.

  12. Comorbidity and cardiovascular risk factors in adult GH deficiency following treatment for Cushing's disease or non-functioning pituitary adenomas during childhood

    DEFF Research Database (Denmark)

    Ragnarsson, Oskar; Höybye, Charlotte; Jönsson, Peter J

    2012-01-01

    Cushing's disease (CD) and non-functioning pituitary adenoma (NFPA) are rare in paediatric patients. The aim of this study was to describe long-term consequences in adults with GH deficiency (GHD) treated for CD or NFPA during childhood.......Cushing's disease (CD) and non-functioning pituitary adenoma (NFPA) are rare in paediatric patients. The aim of this study was to describe long-term consequences in adults with GH deficiency (GHD) treated for CD or NFPA during childhood....

  13. Effects of growth hormone replacement therapy on IGF-related parameters and on the pituitary-gonadal axis in GH-deficient males. A double-blind, placebo-controlled crossover study

    DEFF Research Database (Denmark)

    Juul, A; Andersson, A M; Pedersen, S A

    1998-01-01

    It has been suggested that growth hormone (GH) may play a regulatory role in male reproductive function. To express full anabolic effect in immature boys testosterone apparently requires the presence of GH. In GH-deficient adults, GH replacement therapy exerts a variety of anabolic actions, some...... study in 13 young males with childhood-onset GH deficiency of which 6 had isolated GH deficiency. GH treatment significantly increased serum levels of total IGF-I from 98 (68) to 323 (126) microg/l, free IGF-I from 0.48 (0.47) to 2.24 (1.66) microg/l, IGFBP-3 from 1,874 (1,178) to 3,520 (778) microg...... in hypogonadal patients substituted with androgens, but GH had no effect on inhibin-B levels. In conclusion, GH replacement therapy in 13 GH-deficient young adult males resulted in significant increases in total and free IGF-I as well as in ALS levels in all patients, but had no significant effect on: (1...

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

    NARCIS (Netherlands)

    Buffart, L.M.; Westendorp, T.; Berg-Emons, van den R.J.; Stam, H.; Roebroeck, M.E.

    2009-01-01

    OBJECTIVE: To explore the main barriers to and facilitators of physical activity in young adults with childhood-onset physical disabilities. DESIGN: Qualitative study using focus groups. PARTICIPANTS: Sixteen persons (12 men and 4 women) aged 22.4 (standard deviation 3.4) years, of whom 50% were

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2018-02-17

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

  17. Molecular basis of adult-onset and chronic GM2 gangliosidoses in patients of Ashkenazi Jewish origin: Substitution of serine for glycine at position 269 of the α-subunit of β-hexosaminidase

    International Nuclear Information System (INIS)

    Paw, B.H.; Kaback, M.M.; Neufeld, E.F.

    1989-01-01

    Chronic and adult-onset G M2 gangliosidoses are neurological disorders caused by marked deficiency of the A isoenzyme of β-hexosaminidase; they occur in the Ashkenazi Jewish population, though less frequently than classic (infantile) Tay-Sachs disease. Earlier biosynthetic studies had identified a defective α-subunit that failed to associate with the β-subunit. The authors have now found a guanosine to adenosine transition at the 3' end of exon 7, which causes substitution of serine for glycine at position 269 of the α-subunit. An RNase protection assay was used to localize the mutation to a segment of mRNA from fibroblasts of a patient with the adult-onset disorder. That segment of mRNA (after reverse transcription) and a corresponding segment of genomic DNA were amplified by the polymerase chain reaction and sequenced by the dideoxy method. The sequence analysis, together with an assay based on the loss of a ScrFI restriction site, showed that the patient was a compound heterozygote who had inherited the 269 (Gly → Ser) mutation from his father and an allelic null mutation from his mother. The 269 (Gly → Ser) mutation, in compound heterozygosity with a presumed null allele, was also found in fetal fibroblasts with an association-defective phenotype and in cells from five patients with chronic G M2 gangliosidosis

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

    OpenAIRE

    Yokoyama, Jennifer S.; Lam, Ernest T.; 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 huma...

  19. Immune response to pneumococcal polysaccharides 4 and 14 in elderly and young adults. I Antibody concentrations, avidity and functional activity

    Directory of Open Access Journals (Sweden)

    Carlone George M

    2005-06-01

    Full Text Available Abstract Streptococcus pneumoniae is a serious worldwide pathogen and the focus of numerous vaccine development projects. Currently the most widely accepted surrogate marker for evaluating the efficacy of a given vaccine is to utilize ELISA. Measurement of antibody concentration by ELISA without reduction in cross-reactive antibodies causes an overestimation of antibody concentration and therefore protection, this is most notable in the aged, an at risk group for this infection. We compared the immune response to the pneumococcal polysaccharides (PPS 4 and 14 of 20 young to 20 elderly adults. Pre-and post-vaccination IgG antibody concentrations and antibody avidity against PPS4 and PPS14 were measured using two different enzyme-linked immunosorbant assay (ELISA absorption protocols. All sera were pre-absorbed with either cell-wall polysaccharide (CPS, or CPS and serotype 22F polysaccharide. Pre- and post-vaccination IgG antibody concentrations for serotype 4, but not 14, were significantly lowered with the additional absorption with serotype 22F polysaccharide in both age groups. Young and elderly demonstrated a significant increase from pre- to post-immunization antibody concentration, using either absorption method; and opsonophagocytic antibody titers in response to both PPS4 and PPS14. The correlation coefficients between ELISA and opsonophagocytic assays were improved by additional absorption with serotype 22F in response to serotype 4, but not serotype 14 in all age groups. Opsonophagocytic antibody titers in a sub-group of elderly (>77 years of age were significantly lower than the opsonophagocytic antibody concentrations in young adults. These results suggest the importance of eliminating cross-reactive antibodies from ELISA measurements by absorption of serum and an age-related impairment in the antibody response to pneumococcal polysaccharides.

  20. Abnormal functional connectivity of the amygdala in first-episode and untreated adult major depressive disorder patients with different ages of onset.

    Science.gov (United States)

    Ye, Jing; Shen, Zonglin; Xu, Xiufeng; Yang, Shuran; Chen, Wei; Liu, Xiaoyan; Lu, Yi; Liu, Fang; Lu, Jin; Li, Na; Sun, Xuejin; Cheng, Yuqi

    2017-03-01

    Major depressive disorder (MDD) is a common mental disorder with high morbidity. As a part of the limbic system, the amygdala is important in the processing of emotional information. Structural and functional connectivity (FC) abnormalities in the amygdala have been observed in MDD patients. The present study was carried out to identify the features of amygdala FC in adult MDD patients with different ages of onset. Sixty-nine first-episode and untreated MDD patients and 81 healthy controls (CTLs) were included in this study and underwent 3D structural imaging and resting-state functional MRI scanning. The patients and CTLs were divided into two groups according to age of onset: young adult (abnormal resting-state FC with other regions compared with matched controls. However, in old adult patients, compared with matched controls, the right amygdala showed more abnormal changes in the resting-state FC with other regions. MDD patients with different ages of onset showed different changes in the structure and FC of the amygdala. These results might help us to understand the high heterogeneity of MDD.

  1. Role of complement and antibodies in controlling infection with pathogenic simian immunodeficiency virus (SIV in macaques vaccinated with replication-deficient viral vectors

    Directory of Open Access Journals (Sweden)

    Strasak Alexander

    2009-06-01

    Full Text Available Abstract Background We investigated the interplay between complement and antibodies upon priming with single-cycle replicating viral vectors (SCIV encoding SIV antigens combined with Adeno5-SIV or SCIV pseudotyped with murine leukemia virus envelope boosting strategies. The vaccine was applied via spray-immunization to the tonsils of rhesus macaques and compared with systemic regimens. Results Independent of the application regimen or route, viral loads were significantly reduced after challenge with SIVmac239 (p Conclusion The heterologous prime-boost strategy with replication-deficient viral vectors administered exclusively via the tonsils did not induce any neutralizing antibodies before challenge. However, after challenge, comparable SIV-specific humoral immune responses were observed in all vaccinated animals. Immunization with single cycle immunodeficiency viruses mounts humoral immune responses comparable to live-attenuated immunodeficiency virus vaccines.

  2. Should we start and continue growth hormone (GH) replacement therapy in adults with GH deficiency?

    NARCIS (Netherlands)

    ter Maaten, JC

    2000-01-01

    During the last decade, growth hormone deficiency (GHD) in adults has been described as a clinical syndrome. Central features of this entity include increased fat mass, reduced muscle and bone mass, as well as impaired exercise capacity and quality of life. GH replacement therapy has been initiated

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

    Science.gov (United States)

    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.

  4. Immunohistochemistry for PMS2 and MSH6 alone can replace a four antibody panel for mismatch repair deficiency screening in colorectal adenocarcinoma.

    Science.gov (United States)

    Hall, Geoffrey; Clarkson, Adele; Shi, Amanda; Langford, Eileen; Leung, Helen; Eckstein, Robert P; Gill, Anthony J

    2010-01-01

    Currently, testing for mismatch repair deficiency in colorectal cancers is initiated by performing immunohistochemistry with four antibodies (MLH1, PMS2, MSH2 and MSH6). If any one of these stains is negative the tumour is considered microsatellite unstable and, if clinical circumstances warrant it, the patient is offered genetic testing for Lynch's syndrome. Due to the binding properties of the mismatch repair heterodimer complexes, gene mutation and loss of MLH1 and MSH2 invariably result in the degradation of PMS2 and MSH6, respectively, but the converse is not true. We propose that staining for PMS2 and MSH6 alone will be sufficient to detect all cases of mismatch repair deficiency and should replace routine screening with all four antibodies. The electronic database of the department of Anatomical Pathology, Royal North Shore Hospital, Sydney, Australia, was searched for all colorectal carcinomas on which a four panel immunohistochemical microsatellite instability screen was performed. An audit of the slides for concordant loss of MLH1-PMS2 and MSH2-MSH6 was then undertaken. Unusual or discordant cases were reviewed and, in some cases, re-stained to confirm the staining pattern. Of 344 cases of colorectal cancer which underwent four antibody immunohistochemistry, 104 displayed loss of at least one mismatch repair protein. Of these, 100 showed concordant mismatch repair loss (i.e., loss of MLH1 and PMS2 or loss of MSH2 and MSH6). The four discordant cases comprised two single negative cases (1 MSH6 negative/MSH2 positive case, 1 PMS2 negative/MLH1 positive) and two triple negative (both MLH1/PMS2/MSH6 negative). The microsatellite instability (MSI) group showed a relatively high median age (69.3 years) due to the departmental policy of testing all cases with possible MSI morphology regardless of age. The sensitivity and specificity of a two panel test comprised of PMS2 and MSH6, compared to a four panel test, is 100%. No false negatives or positives were

  5. A serial study of anticardiolipin antibody and antimitochondrial antibody type M5 in a patient with polyarthritis and polymyositis.

    Science.gov (United States)

    Keane, A; Woods, R; Foley-Nolan, D; Roden, D; Coughlan, R; Barry, C

    1989-04-01

    A 22-year-old female presented with polyarthritis and subsequent polymyositis. Initially, she had moderately high levels of anticardiolipin (aCl) and antimitochondrial antibody (AMA) type M5. Following corticosteroid therapy, the anticardiolipin antibody rapidly fell to background levels but reappeared with the onset of two significant clinical events.

  6. Adult vitamin D deficiency exacerbates impairments caused by social stress in BALB/c and C57BL/6 mice.

    Science.gov (United States)

    Groves, Natalie J; Zhou, Mei; Jhaveri, Dhanisha J; McGrath, John J; Burne, Thomas H J

    2017-12-01

    Vitamin D deficiency is prevalent in adults throughout the world. Epidemiological studies have shown significant associations between vitamin D deficiency and an increased risk of various neuropsychiatric and neurodegenerative disorders, such as schizophrenia, depression, Alzheimer's disease and cognitive impairment. However, studies based on observational epidemiology cannot address questions of causality; they cannot determine if vitamin D deficiency is a causal factor leading to the adverse health outcome. The main aim of this study was to determine if AVD deficiency would exacerbate the effects of a secondary exposure, in this case social stress, in BALB/c mice and in the more resilient C57BL/6 mice. Ten-week old male BALB/c and C57BL/6 mice were fed a control or vitamin D deficient diet for 10 weeks, and the mice were further separated into one of two groups for social treatment, either Separated (SEP) or Social Defeat (DEF). SEP mice were placed two per cage with a perforated Plexiglas divider, whereas the DEF mice underwent 10days of social defeat prior to behavioural testing. We found that AVD-deficient mice were more vulnerable to the effects of social stress using a social avoidance test, and this was dependent on strain. These results support the hypothesis that vitamin D deficiency may exacerbate behavioural outcomes in mice vulnerable to stress, a finding that can help guide future studies. Importantly, these discoveries support the epidemiological link between vitamin D deficiency and neuropsychiatric and neurodegenerative disorders; and has provided clues that can guide future studies related to unravelling the mechanisms of action linking adult vitamin D deficiency and adverse brain related outcomes. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  7. Higher visceral fat area increases the risk of vitamin D insufficiency and deficiency in Chinese adults.

    Science.gov (United States)

    Zhang, Meilin; Li, Ping; Zhu, Yufeng; Chang, Hong; Wang, Xuan; Liu, Weiqiao; Zhang, Yuwen; Huang, Guowei

    2015-01-01

    Visceral fat area (VFA), a novel sex-specific index for visceral fat obesity (VFO) might play a major role in the development of vitamin D deficiency. However, the association between VFA and vitamin D insufficiency and deficiency in Chinese population is less clear. The aim of this study was to explore the population-level association between VFA and vitamin D insufficiency and deficiency among Chinese men and women. This cross-sectional study involved 1105 adults aged 20-70 years living in Tianjin who were randomly selected and medically examined. All subjects underwent the bioelectrical impedance analysis (BIA) method to estimate the VFA. Serum 25-hydroxyvitamin D3 (25(OH) D3) level was assayed by the high-performance liquid chromatography (HPLC) method and defined insufficiency and deficiency following recommended cutoffs. The association between VFA and vitamin D insufficiency and deficiency was estimated using binary regression analysis. The total prevalence of vitamin D insufficiency (25(OH) D3: 20-29 μg/L) and deficiency (25(OH) D3  0.05). Moreover, increased VFA was observed to be associated with higher vitamin D insufficiency or deficiency risk with a positive dose-response trend (P for trend convenience surrogate marker for visceral adipose measurement and could be used in identifying the risk of vitamin D insufficiency and deficiency in routine health examination.

  8. A Historical Cohort Study on the Efficacy of Glucocorticoids and Riboflavin Among Patients with Late-onset Multiple Acyl-CoA Dehydrogenase Deficiency

    Institute of Scientific and Technical Information of China (English)

    Xin-Yi Liu; Zhi-Qiang Wang; Dan-Ni Wang; Min-Ting Lin; Ning Wang

    2016-01-01

    Background:Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is the most common type of lipid storage myopathies in China.Most patients with late-onset MADD are well responsive to riboflavin.Up to now,these patients are often treated with glucocorticoids as the first-line drug because they are misdiagnosed as polymyositis without muscle biopsy or gene analysis.Although glucocorticoids seem to improve the fatty acid metabolism of late-onset MADD,the objective evaluation of their rationalization on this disorder and comparison with riboflavin treatment are unknown.Methods:We performed a historical cohort study on the efficacy of the two drugs among 45 patients with late-onset MADD,who were divided into glucocorticoids group and riboflavin group.Detailed clinical information of baseline and 1-month follow-up were collected.Results:After 1-month treatment,a dramatic improvement of muscle strength was found in riboflavin group (P < 0.05).There was no significant difference in muscle enzymes between the two groups.Significantly,the number of patients with full recovery in glucocorticoids group was less than the number in riboflavin group (P < 0.05).On the other hand,almost half of the patients in riboflavin group still presented high-level muscle enzymes and weak muscle strength after 1-month riboflavin treatment,meaning that 1-month treatment duration maybe insufficient and patients should keep on riboflavin supplement for a longer time.Conclusions:Our results provide credible evidences that the overall efficacy of riboflavin is superior to glucocorticoids,and a longer duration of riboflavin treatment is necessary for patients with late-onset MADD.

  9. Onset of diabetes mellitus in children population in the Republic of Mordovia

    Directory of Open Access Journals (Sweden)

    Yelena S. Samоshkina

    2017-09-01

    Full Text Available Introduction: Type 1 diabetes mellitus (T1DM in children is a cause of early disability and high mortality in people of working age. There was an increase in incidence of type 1 diabetes worldwide while increasing the number of patients from South to North and from East to West. The maximum number of patients is in the Nordic countries. However, identified exceptions (e.g. Sardinia justify the need for continuing epidemiological studies in the Russian Federation, where the detaled information has began to emerge only in recent years. Materials and Methods: A retrospective analysis of 134 case histories of children with newly diagnosed diabetes in Endocrinological Department of Children’s Republican Clinical Hospital during the period from 2005 to 2014 was carried out. All children underwent a comprehensive laboratory and instrumental examination with daily monitoring of blood glucose, determination of ionic composition, concentration of C-peptide, antibody to GAD, insulin levels, glycated hemoglobin, and glycosuria ketonuria. Results: According to the study the duration of diabetes from the onset of the first symptoms to the verification of the diagnosis was more than 3 weeks. A classic clinical picture is characterized with a predominance of symptoms of dehydration and energy deficiency, hyperglycemia, hypoinsulinemia and increase the level of antibodies to components of the beta cells. Discussion and Conclusions: Despite the presence of a clear and peculiar clinical picture, a late appeal for medical help in children with diabetes mellitus demonstrates that it contributes to the high frequency of decompensated ketoacidosis in children at disease onset. It is necessary to raise the awareness of health professionals and the public for timely diagnosis of diabetes in children.

  10. Adult Brtl/+ mouse model of osteogenesis imperfecta demonstrates anabolic response to sclerostin antibody treatment with increased bone mass and strength.

    Science.gov (United States)

    Sinder, B P; White, L E; Salemi, J D; Ominsky, M S; Caird, M S; Marini, J C; Kozloff, K M

    2014-08-01

    Treatments to reduce fracture rates in adults with osteogenesis imperfecta are limited. Sclerostin antibody, developed for treating osteoporosis, has not been explored in adults with OI. This study demonstrates that treatment of adult OI mice respond favorably to sclerostin antibody therapy despite retention of the OI-causing defect. Osteogenesis imperfecta (OI) is a heritable collagen-related bone dysplasia, characterized by brittle bones with increased fracture risk. Although OI fracture risk is greatest before puberty, adults with OI remain at risk of fracture. Antiresorptive bisphosphonates are commonly used to treat adult OI, but have shown mixed efficacy. New treatments which consistently improve bone mass throughout the skeleton may improve patient outcomes. Neutralizing antibodies to sclerostin (Scl-Ab) are a novel anabolic therapy that have shown efficacy in preclinical studies by stimulating bone formation via the canonical wnt signaling pathway. The purpose of this study was to evaluate Scl-Ab in an adult 6 month old Brtl/+ model of OI that harbors a typical heterozygous OI-causing Gly > Cys substitution on Col1a1. Six-month-old WT and Brtl/+ mice were treated with Scl-Ab (25 mg/kg, 2×/week) or Veh for 5 weeks. OCN and TRACP5b serum assays, dynamic histomorphometry, microCT and mechanical testing were performed. Adult Brtl/+ mice demonstrated a strong anabolic response to Scl-Ab with increased serum osteocalcin and bone formation rate. This anabolic response led to improved trabecular and cortical bone mass in the femur. Mechanical testing revealed Scl-Ab increased Brtl/+ femoral stiffness and strength. Scl-Ab was successfully anabolic in an adult Brtl/+ model of OI.

  11. Selective alteration of adult hippocampal neurogenesis and impaired spatial pattern separation performance in the RSK2-deficient mouse model of Coffin-Lowry syndrome.

    Science.gov (United States)

    Castillon, Charlotte; Lunion, Steeve; Desvignes, Nathalie; Hanauer, André; Laroche, Serge; Poirier, Roseline

    2018-07-01

    Adult neurogenesis is involved in certain hippocampus-dependent cognitive functions and is linked to psychiatric diseases including intellectual disabilities. The Coffin-Lowry syndrome (CLS) is a developmental disorder caused by mutations in the Rsk2 gene and characterized by intellectual disabilities associated with growth retardation. How RSK2-deficiency leads to cognitive dysfunctions in CLS is however poorly understood. Here, using Rsk2 Knock-Out mice, we characterized the impact of RSK2 deficiency on adult hippocampal neurogenesis in vivo. We report that the absence of RSK2 does not affect basal proliferation, differentiation and survival of dentate gyrus adult-born neurons but alters the maturation progression of young immature newborn neurons. Moreover, when RSK2-deficient mice were submitted to spatial learning, in contrast to wild-type mice, proliferation of adult generated neurons was decreased and no pro-survival effect of learning was observed. Thus, learning failed to recruit a selective population of young newborn neurons in association with deficient long-term memory recall. Given the proposed role of the dentate gyrus and of adult-generated newborn neurons in hippocampal-dependent pattern separation function, we explored this function in a delayed non-matching to place task and in an object-place pattern separation task and report severe deficits in spatial pattern separation in Rsk2-KO mice. Together, this study reveals a previously unknown role for RSK2 in the early stages of maturation and learning-dependent involvement of adult-born dentate gyrus neurons. These alterations associated with a deficit in the ability of RSK2-deficient mice to finely discriminate relatively similar spatial configurations, may contribute to cognitive dysfunction in CLS. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Mutation of the human mitochondrial phenylalanine-tRNA synthetase causes infantile-onset epilepsy and cytochrome c oxidase deficiency.

    Science.gov (United States)

    Almalki, Abdulraheem; Alston, Charlotte L; Parker, Alasdair; Simonic, Ingrid; Mehta, Sarju G; He, Langping; Reza, Mojgan; Oliveira, Jorge M A; Lightowlers, Robert N; McFarland, Robert; Taylor, Robert W; Chrzanowska-Lightowlers, Zofia M A

    2014-01-01

    Mitochondrial aminoacyl-tRNA synthetases (aaRSs) are essential enzymes in protein synthesis since they charge tRNAs with their cognate amino acids. Mutations in the genes encoding mitochondrial aaRSs have been associated with a wide spectrum of human mitochondrial diseases. Here we report the identification of pathogenic mutations (a partial genomic deletion and a highly conserved p. Asp325Tyr missense variant) in FARS2, the gene encoding mitochondrial phenylalanyl-tRNA synthetase, in a patient with early-onset epilepsy and isolated complex IV deficiency in muscle. The biochemical defect was expressed in myoblasts but not in fibroblasts and associated with decreased steady state levels of COXI and COXII protein and reduced steady state levels of the mt-tRNA(Phe) transcript. Functional analysis of the recombinant mutant p. Asp325Tyr FARS2 protein showed an inability to bind ATP and consequently undetectable aminoacylation activity using either bacterial tRNA or human mt-tRNA(Phe) as substrates. Lentiviral transduction of cells with wildtype FARS2 restored complex IV protein levels, confirming that the p.Asp325Tyr mutation is pathogenic, causing respiratory chain deficiency and neurological deficits on account of defective aminoacylation of mt-tRNA(Phe). © 2013. Published by Elsevier B.V. All rights reserved.

  13. Tract-based spatial statistics analysis of diffusion-tensor imaging data in pediatric- and adult-onset multiple sclerosis.

    Science.gov (United States)

    Aliotta, Rachel; Cox, Jennifer L; Donohue, Katelyn; Weinstock-Guttman, Bianca; Yeh, E Ann; Polak, Paul; Dwyer, Michael G; Zivadinov, Robert

    2014-01-01

    White matter (WM) microstructure may vary significantly in pediatric-onset (PO) and adult-onset (AO) patients with multiple sclerosis (MS), a difference that could be explained by the effects of an inherent plasticity in the affected pediatric brains early in the disease, and a phenomenon that does not occur later in life. This hypothesis would support the observation that disease progression is much slower in POMS compared to AOMS patients. To examine WM microstructure in the brain of adults with POMS and AOMS, using tract based spatial statistics (TBSS) analysis of diffusion-tensor imaging (DTI). Adults with relapsing-remitting (RR) POMS, who were diagnosed before age of 18 years (n = 16), were compared with age-matched (AOA, n = 23) and disease duration-matched (AOD, n = 22) RR patients who developed MS after the age of 18 years. Scans were analyzed using the FSL software package (Oxford, UK) and statistics were performed using TBSS to evaluate WM microstructure between groups based on the mean fractional anisotropy (FA) values obtained from the DTI. Widespread cortical and deep WM area differences characterized by increased FA values were seen in the AOAMS compared with POMS group (P < 0.05, TFCE corrected). Significantly increased FA values of posterior WM areas were detected in the AODMS compared with POMS group (P < 0.05, TFCE corrected). Increased FA values in WM areas of the AOMS compared with the POMS patients suggest that diffuse WM microstructure changes are more attributable to age of onset than a simple function of disease duration and age. Copyright © 2012 Wiley Periodicals, Inc.

  14. Juvenile-onset hypothyroidism in a dog

    International Nuclear Information System (INIS)

    Greco, D.S.; Peterson, M.E.; Cho, D.Y.; Markovits, J.E.

    1985-01-01

    Juvenile-onset hypothyroidism was diagnosed in an adult mixed-breed dog examined because of quadraparesis. Unusual clinical signs attributable to juvenile-onset or congenital hypothyroidism included disproportionate dwarfism; enlarged, protruding tongue; mental dullness; and retention of a 'puppy' coat, which was soft and fluffy, without guard hairs. Radiography of the vertebral column and long bones revealed multiple areas of delayed epiphyseal closure and epiphyseal dysgenesis. Myelography demonstrated several intervertebral disk protrusions in the cervical and lumbar regions. Hypothyroidism was confirmed on the basis of a low basal serum thyroxine concentration that failed to increase after the administration of thyroid stimulating hormone. Other laboratory abnormalities included nonregenerative, normocytic, normochromic anemia; mild hypercalcemia; and an impaired growth hormone (GH) secretory response after xylazine administration. At necropsy, the thyroid gland was small and weighed only 0.2g. Microscopic examination of the thyroid gland revealed a loss of glandular tissue, which was replaced by adipose tissue along its periphery. Gross or microscopic abnormalities were not noted in the pituitary gland, and immunohistochemical staining of the pituitary gland revealed a normal number of GH-containing acidophils. This suggests that primary hypothyroidism may result in an impaired secretion of growth hormone, and that pituitary dwarfism or GH deficiency may be difficult to differentiate from hypothyroid dwarfism on the basis of provocative GH testing alone

  15. Antibody titers for canine parvovirus type-2, canine distemper virus, and canine adenovirus type-1 in adult household dogs.

    Science.gov (United States)

    Taguchi, Masayuki; Namikawa, Kazuhiko; Maruo, Takuya; Orito, Kensuke; Lynch, Jonathan; Sahara, Hiroeki

    2011-09-01

    Serum antibody titers for canine parvovirus type-2 (CPV-2), canine distemper virus (CDV) and canine adenovirus type-1 (CAV-1) were investigated in 1031 healthy adult household dogs (2 to 18 years old) given an annual inoculation in the previous 11 to 13 months. The number of dogs retaining significant titers of antibodies against CPV-2, CDV, and CAV-1 were 888 (86%), 744 (72%), and 732 (71%), respectively. There were no differences between males and females in antibody titers against the 3 viruses. Antibody titer for CPV-2 was significantly higher in younger dogs than in older dogs, CDV antibody was significantly higher in older dogs than in younger dogs, and CAV titer was not associated with age.

  16. Safety and convenience of once-weekly somapacitan in adult GH deficiency: a 26-week randomized, controlled trial.

    Science.gov (United States)

    Johannsson, Gudmundur; Feldt-Rasmussen, Ulla; Håkonsson, Ida Holme; Biering, Henrik; Rodien, Patrice; Tahara, Shigeyuki; Toogood, Andrew; Rasmussen, Michael Højby

    2018-05-01

    Somapacitan is a reversible albumin-binding growth hormone (GH) derivative, developed for once-weekly administration. This study aimed to evaluate the safety of once-weekly somapacitan vs once-daily Norditropin ® . Local tolerability and treatment satisfaction were also assessed. 26-week randomized, controlled phase 3 safety and tolerability trial in six countries (Nbib2382939). Male or female patients aged 18-79 years with adult GH deficiency (AGHD), treated with once-daily GH for ≥6 months, were randomized to once-weekly somapacitan ( n  = 61) or once-daily Norditropin ( n  = 31) administered subcutaneously by pen. Both treatments were dose titrated for 8 weeks to achieve insulin-like growth factor I (IGF-I) standard deviation score (SDS) levels within the normal range, and then administered at a fixed dose. Outcome measures were adverse events (AEs), including injection site reactions; occurrence of anti-somapacitan/anti-GH antibodies and change in treatment satisfaction, assessed using the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9). Mean IGF-I SDS remained between 0 and 2 SDS throughout the trial in both groups. AEs were mostly mild or moderate and transient in nature. The most common AEs were nasopharyngitis, headache and fatigue in both groups. More than 1500 somapacitan injections were administered and no clinically significant injection site reactions were reported. No anti-somapacitan or anti-GH antibodies were detected. The TSQM-9 score for convenience increased significantly more with somapacitan vs Norditropin ( P  = 0.0171). In this 26-week trial in patients with AGHD, somapacitan was well tolerated and no safety issues were identified. Once-weekly somapacitan was reported to be more convenient than once-daily Norditropin. © 2018 The authors.

  17. Oral and dental health status in patients with primary antibody deficiencies.

    Science.gov (United States)

    Meighani, Ghasem; Aghamohammadi, Asghar; Javanbakht, Honarmand; Abolhassani, Hassan; Nikayin, Sina; Jafari, Seyed Mehryar; Ghandehari Motlagh, Mehdi; Shamshiri, Ahmad Reza; Rezaei, Nima

    2011-12-01

    Primary antibody deficiencies (PAD) are a group of immune system disorders, associated with decreased levels of secretory and protective immunoglobulins. Because of the important role of immunoglobulins in the protection of oral cavity, patients with PADs are more susceptible to dental caries or oral manifestations. This study was performed to investigate the oral and dental manifestations of PADs patients. In this study, 33 patients with PADs (21 common variable immunodeficiency, 8 X-linked agammaglobulinemia and 4 hyper IgM syndrome) and 66 controls were examined; the number of decayed, missed and filled teeth (DMFT) were investigated. Aphthous was the most frequent manifestation in PADs patients (38.7%), which was significantly 16.7% higher than the controls (p=0.03). The patients with PADs showed significantly higher presentation of other oral and dental manifestations, including herpes sores, candidiasis tonsillitis, gingivitis, calculus, enamel hypoplasia and other ulcerations. The mean DMFT scores were 6.15±3.6 and 1.93±0.4 in PADs patients and controls, respectively (p<0.001). Although the patients with common variable immunodeficiency had higher means of DMFT in comparison with other groups of PADs, this difference was not statistically significant. This study showed significantly higher frequency of oral and dental manifestations in the patients with PADs compared to controls. Therefore, regular examination of oral cavity could be suggested in this group of immunodeficient patients.

  18. Enhanced Contribution of HLA in Pediatric Onset Ulcerative Colitis.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  20. Adult-onset hypophosphatemic osteomalacia associated with Sjogren syndrome

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Y. Zhu

    2012-05-01

    Full Text Available 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, 5μg T4/100 g body weight (BW treated group, 20 μg T4/100g 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 T4/100g 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 T4/100g 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.

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

    Directory of Open Access Journals (Sweden)

    Neslihan Edeer Karaca

    2016-01-01

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

  3. Differences between early and late onset adult depression

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  4. Ontogeny of thymic independent antibody responses in vitro in normal mice and mice with an x-linked B cell defect

    Energy Technology Data Exchange (ETDEWEB)

    Mosier, D.E.; Mond, J.J.; Goldings, E.A.

    1977-12-01

    The primary in vitro antibody response of neonatal spleen cells to three thymic independent antigens has been examined. The time of onset of responsiveness to TNP-Brucella abortus and TNP-lipopolysaccharide was significantly earlier than the onset of responsiveness to TNP-Ficoll. This ontologic sequence was not affected by T cell depletion or antigen presentation on adult macrophages. In neonatal mice bearing the X-linked CBA/N defect, the response to TNP-Brucella abortus and TNP-lipopolysaccharide was much delayed and no response to TNP-Ficoll developed. We conclude that different thymic independent antigens address different subpopulations of B cells, one of which appears earlier in ontogeny than the other.

  5. Ontogeny of thymic independent antibody responses in vitro in normal mice and mice with an x-linked B cell defect

    International Nuclear Information System (INIS)

    Mosier, D.E.; Mond, J.J.; Goldings, E.A.

    1977-01-01

    The primary in vitro antibody response of neonatal spleen cells to three thymic independent antigens has been examined. The time of onset of responsiveness to TNP-Brucella abortus and TNP-lipopolysaccharide was significantly earlier than the onset of responsiveness to TNP-Ficoll. This ontologic sequence was not affected by T cell depletion or antigen presentation on adult macrophages. In neonatal mice bearing the X-linked CBA/N defect, the response to TNP-Brucella abortus and TNP-lipopolysaccharide was much delayed and no response to TNP-Ficoll developed. We conclude that different thymic independent antigens address different subpopulations of B cells, one of which appears earlier in ontogeny than the other

  6. Clinical Onset of Celiac Disease after an Episode of Campylobacter jejuni Enteritis

    Directory of Open Access Journals (Sweden)

    EF Verdu

    2007-01-01

    Full Text Available The present report describes a young woman with no previous gastrointestinal complaints who was initially diagnosed with postinfective irritable bowel syndrome (IBS after a confirmed case of Campylobacter jejuni enteritis. However, because of persistent diarrhea, new-onset bloating and the development of iron and vitamin deficiencies, serological markers for celiac disease (CD were evaluated. A positive tissue transglutaminase immunoglobulin A antibody test and repeat endoscopy with duodenal biopsy showing a Marsh IIIa lesion confirmed the diagnosis of CD. Infectious gastroenteritis is a well-established risk factor for the development of IBS, and there is recent evidence that it could play a role in the initiation and exacerbation of inflammatory bowel disease. The present case suggests that the clinical expression of CD can be unmasked by an acute gastrointestinal infection and supports the hypothesis that environmental factors other than gliadin may play a role in the clinical onset of CD in a genetically susceptible host. The increasing availability of serological testing and upper endoscopy has led to increasingly frequent diagnoses of CD and recognition that it may mimic IBS. The present case findings suggest that CD should be considered in the differential diagnosis of persistent IBS-like symptoms after an episode of infectious gastroenteritis.

  7. Molecular basis of adult-onset and chronic G sub M2 gangliosidoses in patients of Ashkenazi Jewish origin: Substitution of serine for glycine at position 269 of the. alpha. -subunit of. beta. -hexosaminidase

    Energy Technology Data Exchange (ETDEWEB)

    Paw, B.H.; Kaback, M.M.; Neufeld, E.F. (Univ. of California, Los Angeles (USA))

    1989-04-01

    Chronic and adult-onset G{sub M2} gangliosidoses are neurological disorders caused by marked deficiency of the A isoenzyme of {beta}-hexosaminidase; they occur in the Ashkenazi Jewish population, though less frequently than classic (infantile) Tay-Sachs disease. Earlier biosynthetic studies had identified a defective {alpha}-subunit that failed to associate with the {beta}-subunit. The authors have now found a guanosine to adenosine transition at the 3{prime} end of exon 7, which causes substitution of serine for glycine at position 269 of the {alpha}-subunit. An RNase protection assay was used to localize the mutation to a segment of mRNA from fibroblasts of a patient with the adult-onset disorder. That segment of mRNA (after reverse transcription) and a corresponding segment of genomic DNA were amplified by the polymerase chain reaction and sequenced by the dideoxy method. The sequence analysis, together with an assay based on the loss of a ScrFI restriction site, showed that the patient was a compound heterozygote who had inherited the 269 (Gly {yields} Ser) mutation from his father and an allelic null mutation from his mother. The 269 (Gly {yields} Ser) mutation, in compound heterozygosity with a presumed null allele, was also found in fetal fibroblasts with an association-defective phenotype and in cells from five patients with chronic G{sub M2} gangliosidosis.

  8. Deficiência de ferro nas afecções gastrointestinais do adulto Iron deficiency related to gastrointestinal diseases in adults

    Directory of Open Access Journals (Sweden)

    Cyrla Zaltman

    2010-06-01

    Full Text Available A anemia por deficiência de ferro (ADF ou a deficiência de ferro (DF isolada são comuns em crianças e mulheres pré-menopausa. Entretanto, em adultos do sexo masculino e mulheres pós-menopausa, essa condição se associa frequentemente a perdas sanguíneas gastrointestinais ou mal absorção. A prevalência das lesões gastrointestinais torna essencial o exame do aparelho digestório superior e inferior através da endoscopia. Investigações complementares devem ser realizadas se os procedimentos endoscópicos não evidenciarem sangramento em situações clínicas, tais como a necessidade de múltiplas hemotransfusões, a ausência de sangramento visível à endoscopia digestiva alta e colonoscopia e a falta de resposta à reposição de ferro.Esses casos devem ser direcionados para investigação do intestino delgado com métodos radiológicos ou, mais recentemente, com a cápsula endoscópica e da enteroscopia com duplo balão. A cintigrafia com hemácias marcadas e a angiografia têm papel restrito, sendo utilizadas apenas no sangramento aberto. O tratamento varia de acordo com a etiologia, a intensidade da perda sanguínea e da deficiência de ferro.Iron deficiency anaemia and isolated iron deficiency are common in children and pre-menopausal women. However, in male adults and post-menopausal women this condition is most frequently caused by gastrointestinal blood loss or malabsorption. The prevalence of gastrointestinal lesions makes the examination by endoscopy of both upper and lower gastrointestinal tracts essential. Further investigations, when the initial exams are negative, are only warranted in cases of multiple transfusions, visible blood loss or lack of response to oral iron supplementation. In these cases examinations should be focused on the small bowel by radiological methods or more recently using capsule endoscopy and double balloon enteroscopy. Nuclear medicine and angiography have a limited role to play in this

  9. GAD antibody-associated limbic encephalitis in a young woman with APECED

    Directory of Open Access Journals (Sweden)

    Anna Kopczak

    2017-05-01

    Full Text Available The autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED syndrome is a genetic disorder caused by a mutation in the autoimmune regulator (AIRE gene. Immune deficiency, hypoparathyroidism and Addison’s disease due to autoimmune dysfunction are the major clinical signs of APECED. We report on a 21-year-old female APECED patient with two inactivating mutations in the AIRE gene. She presented with sudden onset of periodic nausea. Adrenal insufficiency was diagnosed by means of the ACTH stimulation test. Despite initiation of hormone replacement therapy with hydrocortisone and fludrocortisone, nausea persisted and the patient developed cognitive deficits and a loss of interest which led to the diagnosis of depression. She was admitted to the psychiatric department for further diagnostic assessment. An EEG showed a focal epileptic pattern. Glutamic acid decarboxylase (GAD antibodies, which had been negative eight years earlier, were now elevated in serum and in the cerebrospinal fluid. Oligoclonal bands were positive indicating an inflammatory process with intrathecal antibody production in the central nervous system (CNS. The periodic nausea was identified as dialeptic seizures, which clinically presented as gastrointestinal aura followed by episodes of reduced consciousness that occurred about 3–4 times per day. GAD antibody-associated limbic encephalitis (LE was diagnosed. Besides antiepileptic therapy, an immunosuppressive treatment with corticosteroids was initiated followed by azathioprine. The presence of nausea and vomiting in endocrine patients with autoimmune disorders is indicative of adrenal insufficiency. However, our case report shows that episodic nausea may be a symptom of epileptic seizures due to GAD antibodies-associated LE in patients with APECED.

  10. Functional human antibody CDR fusions as long-acting therapeutic endocrine agonists.

    Science.gov (United States)

    Liu, Tao; Zhang, Yong; Liu, Yan; Wang, Ying; Jia, Haiqun; Kang, Mingchao; Luo, Xiaozhou; Caballero, Dawna; Gonzalez, Jose; Sherwood, Lance; Nunez, Vanessa; Wang, Danling; Woods, Ashley; Schultz, Peter G; Wang, Feng

    2015-02-03

    On the basis of the 3D structure of a bovine antibody with a well-folded, ultralong complementarity-determining region (CDR), we have developed a versatile approach for generating human or humanized antibody agonists with excellent pharmacological properties. Using human growth hormone (hGH) and human leptin (hLeptin) as model proteins, we have demonstrated that functional human antibody CDR fusions can be efficiently engineered by grafting the native hormones into different CDRs of the humanized antibody Herceptin. The resulting Herceptin CDR fusion proteins were expressed in good yields in mammalian cells and retain comparable in vitro biological activity to the native hormones. Pharmacological studies in rodents indicated a 20- to 100-fold increase in plasma circulating half-life for these antibody agonists and significantly extended in vivo activities in the GH-deficient rat model and leptin-deficient obese mouse model for the hGH and hLeptin antibody fusions, respectively. These results illustrate the utility of antibody CDR fusions as a general and versatile strategy for generating long-acting protein therapeutics.

  11. Altered dopamine ontogeny in the developmentally vitamin D deficient rat and its relevance to schizophrenia.

    Science.gov (United States)

    Kesby, James P; Cui, Xiaoying; Burne, Thomas H J; Eyles, Darryl W

    2013-01-01

    Schizophrenia is a heterogeneous group of disorders with unknown etiology. Although abnormalities in multiple neurotransmitter systems have been linked to schizophrenia, alterations in dopamine (DA) neurotransmission remain central to the treatment of this disorder. Given that schizophrenia is considered a neurodevelopmental disorder we have hypothesized that abnormal DA signaling in the adult patient may result from altered DA signaling during fetal brain development. Environmental and genetic risk factors can be modeled in rodents to allow for the investigation of early neurodevelopmental pathogenesis that may lead to clues into the etiology of schizophrenia. To address this we created an animal model of one such risk factor, developmental vitamin D (DVD) deficiency. DVD-deficient adult rats display an altered behavioral profile in response to DA releasing and blocking agents that are reminiscent of that seen in schizophrenia patients. Furthermore, developmental studies revealed that DVD deficiency also altered cell proliferation, apoptosis, and neurotransmission across the embryonic brain. In particular, DVD deficiency reduces the expression of crucial dopaminergic specification factors and alters DA metabolism in the developing brain. We speculate such alterations in fetal brain development may change the trajectory of DA neuron ontogeny to induce the behavioral abnormalities observed in adult offspring. The widespread evidence that both dopaminergic and structural changes are present in people who develop schizophrenia prior to onset also suggest that early alterations in development are central to the disease. Taken together, early alterations in DA ontogeny may represent a core feature in the pathology of schizophrenia. Such a mechanism could bring together evidence from multiple risk factors and genetic vulnerabilities to form a convergent pathway in disease pathophysiology.

  12. Altered dopamine ontogeny in the developmentally vitamin D deficient rat and its relevance to schizophrenia

    Directory of Open Access Journals (Sweden)

    James P. Kesby

    2013-07-01

    Full Text Available Schizophrenia is a heterogeneous group of disorders with unknown aetiology. Although abnormalities in multiple neurotransmitter systems have been linked to schizophrenia, alterations in dopamine neurotransmission remain central to the treatment of this disorder. Given that schizophrenia is considered a neurodevelopmental disorder we have hypothesised that abnormal dopamine signalling in the adult patient may result from altered dopamine signalling during foetal brain development. Environmental and genetic risk factors can be modelled in rodents to allow for the investigation of early neurodevelopmental pathogenesis that may lead to clues into the aetiology of schizophrenia. To address this we created an animal model of one such risk factor, developmental vitamin D (DVD deficiency. DVD-deficient adult rats display an altered behavioural profile in response to dopamine releasing and blocking agents that are reminiscent of that seen in schizophrenia patients. Furthermore, developmental studies revealed that DVD deficiency also altered cell proliferation, apoptosis and neurotransmission across the embryonic brain. In particular, DVD deficiency reduces the expression of crucial dopaminergic specification factors and alters dopamine metabolism in the developing brain. We speculate such alterations in foetal brain development may change the trajectory of dopamine neuron ontogeny to induce the behavioural abnormalities observed in adult offspring. The widespread evidence that both dopaminergic and structural changes are present in people who develop schizophrenia prior to onset also suggest that early alterations in development are central to the disease. Taken together, early alterations in dopamine ontogeny may represent a core feature in the pathology of schizophrenia. Such a mechanism could bring together evidence from multiple risk factors and genetic vulnerabilities to form a convergent pathway in disease pathophysiology.

  13. Early-onset severe obesity with ACTH deficiency and red hair in a boy: the POMC deficiency.

    Science.gov (United States)

    Ozen, S; Aldemir, O

    2012-01-01

    The patient is a 2.8 years old male who is extremely obese and severe hyperphagic from birth. He had seizures attacks and apnea from the second week of his life. He has red hair and serum cortisol and ACTH levels are very low. We examined our patient as a hypocortisolism due to ACTH deficiency and central hypothyrodism. After the corticosteroid replacement therapy hair color changed to brown. We performed molecular genetic analysis at the Institue for Experimental Pediatric Endocrinology laboratory in Berlin, Germany by Krude H. and found compound heterozygous mutations. As a result the case is diagnosed as POMC deficiency.

  14. Adaptation of enterovirus 71 to adult interferon deficient mice.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Caine

    Full Text Available Non-polio enteroviruses, including enterovirus 71 (EV71, have caused severe and fatal cases of hand, foot and mouth disease (HFMD in the Asia-Pacific region. The development of a vaccine or antiviral against these pathogens has been hampered by the lack of a reliable small animal model. In this study, a mouse adapted EV71 strain was produced by conducting serial passages through A129 (α/β interferon (IFN receptor deficient and AG129 (α/β, γ IFN receptor deficient mice. A B2 sub genotype of EV71 was inoculated intraperitoneally (i.p. into neonatal AG129 mice and brain-harvested virus was subsequently passaged through 12 and 15 day-old A129 mice. When tested in 10 week-old AG129 mice, this adapted strain produced 100% lethality with clinical signs including limb paralysis, eye irritation, loss of balance, and death. This virus caused only 17% mortality in same age A129 mice, confirming that in the absence of a functional IFN response, adult AG129 mice are susceptible to infection by adapted EV71 isolates. Subsequent studies in adult AG129 and young A129 mice with the adapted EV71 virus examined the efficacy of an inactivated EV71 candidate vaccine and determined the role of humoral immunity in protection. Passive transfer of rabbit immune sera raised against the EV71 vaccine provided protection in a dose dependent manner in 15 day-old A129 mice. Intramuscular injections (i.m. in five week-old AG129 mice with the alum adjuvanted vaccine also provided protection against the mouse adapted homologous strain. No clinical signs of disease or mortality were observed in vaccinated animals, which received a prime-and-boost, whereas 71% of control animals were euthanized after exhibiting systemic clinical signs (P<0.05. The development of this animal model will facilitate studies on EV71 pathogenesis, antiviral testing, the evaluation of immunogenicity and efficacy of vaccine candidates, and has the potential to establish correlates of protection

  15. KADAR ANTIBODI-TIROPEROKSIDASE DAN ANTIBODI-TIROGLOBULIN PADA WANITA USIA SUBUR DI DAERAH ENDEMlS GAKI

    Directory of Open Access Journals (Sweden)

    Agus Wibowo

    2012-10-01

    Full Text Available Background: Thyroid hormones play a critical role in human. Disorders of the thyroid gland result primary from autoimmune processes that either stimulate the over production of thyroid hormones (hyperthyroid or causes glandular destruction and hormones deficiency (hypothyroid. Autoimmune Thyroid Disease (AITD a common organ specific autoimmune disorder is seen mostly in women. AITD are complex disease that are caused by an interaction between susceptibility genes and environmental trigger such dietary iodine. The development of antibodies to Thyroid peroxidase (TPO and Thyroglobulin (TG is the main hall mark of AITD. Method: 'Thirty respondents from were analyzed. The blood were collected for TSH, FreeT4, Tyroglobulin Antibody and Tyroperoxidase Antibody analyzed and DNA isolation. Circulating TSH, FreeT4, autoantibodies to TPO and TG are measured by ELISA. Result: 50% respondent in normal thyroid hormones and 50% in hypothyroid and hyperthyroid status. TPO antibodies  and thyroglobulin antibodies found in all of respondent with thyroid disorder. Conclusion: Antibodies to TPO and TG is seen in respondent with thyroid disorder   Keywords: AITD, TSH, FreeT4, TPO antibodies, TG antibodies.

  16. A rare presentation of adult onset Still’s disease in an elderly patient

    Directory of Open Access Journals (Sweden)

    Mariya Apostolova

    2011-10-01

    Full Text Available Adult onset Still’s disease (AOSD is a rare inflammatory disorder of unknown etiology that usually affects young adults. Very few patients older than 70-year-old have been reported. Clinical features include quotidian fevers, arthralgias, arthritis, pharyngitis, lymphadenopathy and an evanescent rash. AOSD should be considered in the differential diagnosis of fever of unknown origin. Early diagnosis is often difficult since it is a diagnosis of exclusion and the presence of infectious, neoplastic and autoimmune conditions needs to be ruled out before the diagnosis is made. No specific laboratory tests are available to aid in the diagnosis of AOSD. As a result, a set of diagnostic criteria that define the clinical features of this condition, termed the Yamaguchi criteria, have been most commonly used to establish the diagnosis. We describe the case of a 72-year-old Caucasian male with past medical history significant for generalized anxiety disorder, depression, BPH, and hypertriglyceridemia, who presented to a tertiary institution complaining of profound generalized weakness and weight loss that started three weeks prior to presentation. Initial laboratory studies showed leukocytosis, elevated ESR, CRP, ferritin and liver dysfunction. Cultures, ANA and rheumatoid factor studies were negative. The patient underwent further extensive workup that excluded the presence of infectious, neoplastic and autoimmune disorders and was subsequently diagnosed with AOSD and new onset diabetes mellitus. For the management of AOSD he was started on prednisone with significant improvement in markers of inflammation, symptoms and level of function.

  17. Expanding the clinical spectrum of 3-phosphoglycerate dehydrogenase deficiency

    NARCIS (Netherlands)

    Tabatabaie, L; Klomp, L W J; Rubio-Gozalbo, M E; Spaapen, L J M; Haagen, A A M; Dorland, L; de Koning, T J

    UNLABELLED: 3-Phosphoglycerate dehydrogenase (3-PGDH) deficiency is considered to be a rare cause of congenital microcephaly, infantile onset of intractable seizures and severe psychomotor retardation. Here, we report for the first time a very mild form of genetically confirmed 3-PGDH deficiency in

  18. Structure of the periodontium in cathepsin C-deficient mice

    NARCIS (Netherlands)

    de Haar, Susanne F.; Tigchelaar-Gutter, Wikky; Everts, Vincent; Beertsen, Wouter

    2006-01-01

    Papillon-Lefevre syndrome is characterized by increased susceptibility to early-onset periodontitis and is caused by mutations in the cathepsin C gene. How deficiency of the enzyme relates to an increased periodontal infection risk is still not entirely clear. One possibility is that the deficiency

  19. Intact calcium signaling in adrenergic-deficient embryonic mouse hearts.

    Science.gov (United States)

    Peoples, Jessica N; Taylor, David G; Katchman, Alexander N; Ebert, Steven N

    2018-01-22

    Mouse embryos that lack the ability to produce the adrenergic hormones, norepinephrine (NE) and epinephrine (EPI), due to disruption of the dopamine beta-hydroxylase (Dbh -/- ) gene inevitably perish from heart failure during mid-gestation. Since adrenergic stimulation is well-known to enhance calcium signaling in developing as well as adult myocardium, and impairments in calcium signaling are typically associated with heart failure, we hypothesized that adrenergic-deficient embryonic hearts would display deficiencies in cardiac calcium signaling relative to adrenergic-competent controls at a developmental stage immediately preceding the onset of heart failure, which first appears beginning or shortly after mouse embryonic day 10.5 (E10.5). To test this hypothesis, we used ratiometric fluorescent calcium imaging techniques to measure cytosolic calcium transients, [Ca 2+ ] i in isolated E10.5 mouse hearts. Our results show that spontaneous [Ca 2+ ] i oscillations were intact and robustly responded to a variety of stimuli including extracellular calcium (5 mM), caffeine (5 mM), and NE (100 nM) in a manner that was indistinguishable from controls. Further, we show similar patterns of distribution (via immunofluorescent histochemical staining) and activity (via patch-clamp recording techniques) for the major voltage-gated plasma membrane calcium channel responsible for the L-type calcium current, I Ca,L , in adrenergic-deficient and control embryonic cardiac cells. These results demonstrate that despite the absence of vital adrenergic hormones that consistently leads to embryonic lethality in vivo, intracellular and extracellular calcium signaling remain essentially intact and functional in embryonic mouse hearts through E10.5. These findings suggest that adrenergic stimulation is not required for the development of intracellular calcium oscillations or extracellular calcium signaling through I Ca,L and that aberrant calcium signaling does not likely contribute

  20. Effects of up to 15 years of recombinant human GH (rhGH) replacement on bone metabolism in adults with growth hormone deficiency (GHD): the Leiden Cohort Study.

    Science.gov (United States)

    Appelman-Dijkstra, Natasha M; Claessen, Kim M J A; Hamdy, Neveen A T; Pereira, Alberto M; Biermasz, Nienke R

    2014-11-01

    Growth hormone deficiency (GHD) in adulthood may be associated with a decreased bone mineral density (BMD), a decreased bone mineral content (BMC) and an increased fracture risk. Recombinant human GH (rhGH) replacement induces a progressive increase in BMD for up to 5-7 years of treatment. Data on longer follow-up are, however, scarce. Two hundred and thirty-adult GHD patients (mean age 47·1 years, 52·6% female), of whom 88% patients had adult-onset (AO) GHD, receiving rhGH replacement for ≥5 years were included in the study. Most patients had multiple pituitary hormone deficiencies. Bone turnover markers, BMC and BMD and T-scores at the lumbar spine and femoral neck were evaluated at baseline, and after 5, 10 and 15 years of rhGH replacement. In addition, clinical fracture incidence was assessed. Mean lumbar spine BMD, lumbar spine BMC and T-scores gradually increased during the first 10 years of rhGH replacement and remained stable thereafter. Largest effects of rhGH supplementation were found in men. In the small subset of patients using bisphosphonates, use of bisphosphonates did not impact additional beneficial effects in the long term. Low baseline BMD positively affected the change in BMD and BMC over time, but there was a negative effect of high GH dose at 1 year on the change in BMD and BMC over time. Clinical fracture incidence during long-term rhGH replacement was 20.1/1000 py. Fifteen years of rhGH replacement in GHD adults resulted in a sustained increase in BMD values at the lumbar spine, particularly in men, and stabilization of BMD values at the femoral neck. Clinical fracture incidence was suggested not to be increased during long-term rhGH replacement. © 2014 John Wiley & Sons Ltd.

  1. Life situation of adults with congenital limb reduction deficiency in Sweden.

    Science.gov (United States)

    Sjöberg, Lis; Nilsagård, Ylva; Fredriksson, Carin

    2014-01-01

    To describe the current life situation of adults with congenital limb reduction deficiencies (CLRD), living in Sweden, regarding their main daily occupation, leisure activities and self-reported general health. A cross-sectional survey was conducted using a study-specific questionnaire, sent by post. Hundred and seventeen persons with different extent, forms and levels of CLRD (mean age 33 years) responded to the questionnaire. Work or study was the main occupation for 86% of the participants and 50% had completed a college or university education. About 7% were unemployed and 3% were on sick leave. The participants were highly involved in social and physical activities during leisure time. The majority reported good or very good general health. This study is the first investigation of the life situation of adults with CLRD described with a perspective from Swedish society. The participants were educated and worked to a great extent, which corresponds well to the Swedish population as a whole. Further research is needed, especially with a focus on the internal perspective of life situation, different aspects of work capacity, occurences of strain injuries and the benefit of assistive devices among adults with CLRD. Implications for Rehabilitation People with CLRD require a health care system with a multi-professional rehabilitation team offering regular contact during their life time. Educational system offering study counselling on all education levels (from primary school to university) is an important type of support for people with any kind of deficiency, in order to find suitable education and profession. Work is of importance for an acceptable life situation. Rehabilitation for people with CLRD should emphasise facilitating their ability to work, through engagement in individual personal capacity and self-efficacy. The majority of people with CLRD are users of prostheses and assistive devices. The benefits of the devices are basic but the rehabilitation

  2. Vitamin D Deficiency in Adult Patients with Schizophreniform and Autism Spectrum Syndromes: A One-Year Cohort Study at a German Tertiary Care Hospital.

    Science.gov (United States)

    Endres, Dominique; Dersch, Rick; Stich, Oliver; Buchwald, Armin; Perlov, Evgeniy; Feige, Bernd; Maier, Simon; Riedel, Andreas; van Elst, Ludger Tebartz

    2016-01-01

    Vitamin D has many immunomodulatory, anti-inflammatory, and neuroprotective functions, and previous studies have demonstrated an association between vitamin D deficiency and neuropsychiatric disease. The aim of our study was to analyze the prevalence of vitamin D deficiency in a 1-year cohort of adult inpatients with schizophreniform and autism spectrum syndromes in a naturalistic inpatient setting in Germany. Our study was comprised of 60 adult schizophreniform and 23 adult high-functioning autism spectrum patients who were hospitalized between January and December of 2015. We compared our findings with a historical German reference cohort of 3,917 adults using Pearson's two-sided chi-squared test. The laboratory measurements of 25-hydroxyvitamin D2/3 [25(OH)vitamin D] were obtained using a chemiluminescence immunoassay. In the schizophreniform group, we found decreased (vitamin D levels in 48/60 (80.0%) of the patients. In the autism spectrum group, decreased levels were detected in 18/23 (78.3%) of the patients. 25(OH)vitamin D deficiencies were found in 57.3% of the historical control group. Particularly, severe deficiencies (vitamin D values of >30 ng/ml were observed in only 5% of the schizophreniform patients, 8.7% of the autism spectrum patients, and 21.9% of the healthy controls. We found very high rates of 25(OH)vitamin D deficiencies in both patient groups and have discussed whether our findings might be related to alterations in the immunological mechanisms. Irrespective of the possible pathophysiological links between vitamin D deficiency and schizophrenia or autism spectrum disorders, a more frequent measurement of vitamin D levels seems to be justified in these patient groups. Further prospective, controlled, blinded, and randomized research should be conducted to analyze the effectiveness of vitamin D supplementation on the improvement of psychiatric symptoms.

  3. Circadian variation in serum free and total insulin-like growth factor (IGF)-I and IGF-II in untreated and treated acromegaly and growth hormone deficiency

    DEFF Research Database (Denmark)

    Skjaerbaek, Christian; Frystyk, Jan; Kaal, Andreas

    2000-01-01

    to the nocturnal increase in IGF binding protein-1. In this study we have investigated the circadian variation in circulating free IGF-I and IGF-II in patients with acromegaly and patients with adult onset growth hormone deficiency. PATIENTS: Seven acromegalic patients were studied with and without treatment...... no significant circadian variations in free IGF-I or free IGF-II in either of the two occasions. In contrast, there was a significant circadian variation of total IGF-I after adjustment for changes in plasma volume in both treated and untreated acromegaly and GH deficiency in all cases with a peak between 0300 h...

  4. Neuropsychiatric manifestations in late-onset urea cycle disorder patients

    OpenAIRE

    Serrano Mercedes L.; Martins Cecilia E.; Pérez-Dueñas Belén; Gómez-López Lilian; Murgui Empar; Fons Carmen; García-Cazorla Ángels; Artuch Rafael M D; Jara Fernando; Arranz José Antonio; Häberle Johannes; Briones Paz; Campistol Jaume M D; Pineda Mercè; Vilaseca María Antònia Antonia

    2010-01-01

    Inherited urea cycle disorders represent one of the most common groups of inborn errors of metabolism. Late onset urea cycle disorders caused by partial enzyme deficiencies may present with unexpected clinical phenotypes. We report 9 patients followed up in our hospital presenting late onset urea cycle disorders who initially manifested neuropsychiatric/neurodevelopmental symptoms (the most prevalent neuropsychiatric/neurodevelopmental diagnoses were mental retardation attention deficit hyper...

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

    Science.gov (United States)

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

    2012-10-01

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

  6. Postpartum thyroid dysfunction in pregnant thyroid peroxidase antibody-positive women living in an area with mild to moderate iodine deficiency: is iodine supplementation safe?

    DEFF Research Database (Denmark)

    Nøhr, S B; Jørgensen, A; Pedersen, K M

    2000-01-01

    In moderately iodine-deficient, pregnant, thyroid peroxidase antibody (TPO-Ab)-positive women the role of iodine supplementation in the development of postpartum thyroid dysfunction (PPTD) was studied in a placebo-controlled, randomized, double blind trial. Screening for TPO-Ab was performed......-Ab-positive women living in an area with mild to moderate iodine deficiency did not induce or worsen PPTD. The study confirmed that screening for TPO-Ab in early pregnancy can predict women at high risk for development of PPTD. Udgivelsesdato: 2000-Sep...... microg iodine or no iodine. The +/+ group received iodine during pregnancy and the postpartum period, the +/- group received iodine during pregnancy only, and the -/- group received no iodine supplementation. A total of 66 TPO-Ab positive women were followed, and in the postpartum period sera were...

  7. Immunization Elicits Antigen-Specific Antibody Sequestration in Dorsal Root Ganglia Sensory Neurons

    Science.gov (United States)

    Gunasekaran, Manojkumar; Chatterjee, Prodyot K.; Shih, Andrew; Imperato, Gavin H.; Addorisio, Meghan; Kumar, Gopal; Lee, Annette; Graf, John F.; Meyer, Dan; Marino, Michael; Puleo, Christopher; Ashe, Jeffrey; Cox, Maureen A.; Mak, Tak W.; Bouton, Chad; Sherry, Barbara; Diamond, Betty; Andersson, Ulf; Coleman, Thomas R.; Metz, Christine N.; Tracey, Kevin J.; Chavan, Sangeeta S.

    2018-01-01

    The immune and nervous systems are two major organ systems responsible for host defense and memory. Both systems achieve memory and learning that can be retained, retrieved, and utilized for decades. Here, we report the surprising discovery that peripheral sensory neurons of the dorsal root ganglia (DRGs) of immunized mice contain antigen-specific antibodies. Using a combination of rigorous molecular genetic analyses, transgenic mice, and adoptive transfer experiments, we demonstrate that DRGs do not synthesize these antigen-specific antibodies, but rather sequester primarily IgG1 subtype antibodies. As revealed by RNA-seq and targeted quantitative PCR (qPCR), dorsal root ganglion (DRG) sensory neurons harvested from either naïve or immunized mice lack enzymes (i.e., RAG1, RAG2, AID, or UNG) required for generating antibody diversity and, therefore, cannot make antibodies. Additionally, transgenic mice that express a reporter fluorescent protein under the control of Igγ1 constant region fail to express Ighg1 transcripts in DRG sensory neurons. Furthermore, neural sequestration of antibodies occurs in mice rendered deficient in neuronal Rag2, but antibody sequestration is not observed in DRG sensory neurons isolated from mice that lack mature B cells [e.g., Rag1 knock out (KO) or μMT mice]. Finally, adoptive transfer of Rag1-deficient bone marrow (BM) into wild-type (WT) mice or WT BM into Rag1 KO mice revealed that antibody sequestration was observed in DRG sensory neurons of chimeric mice with WT BM but not with Rag1-deficient BM. Together, these results indicate that DRG sensory neurons sequester and retain antigen-specific antibodies released by antibody-secreting plasma cells. Coupling this work with previous studies implicating DRG sensory neurons in regulating antigen trafficking during immunization raises the interesting possibility that the nervous system collaborates with the immune system to regulate antigen-mediated responses. PMID:29755449

  8. Immunization Elicits Antigen-Specific Antibody Sequestration in Dorsal Root Ganglia Sensory Neurons

    Directory of Open Access Journals (Sweden)

    Manojkumar Gunasekaran

    2018-04-01

    Full Text Available The immune and nervous systems are two major organ systems responsible for host defense and memory. Both systems achieve memory and learning that can be retained, retrieved, and utilized for decades. Here, we report the surprising discovery that peripheral sensory neurons of the dorsal root ganglia (DRGs of immunized mice contain antigen-specific antibodies. Using a combination of rigorous molecular genetic analyses, transgenic mice, and adoptive transfer experiments, we demonstrate that DRGs do not synthesize these antigen-specific antibodies, but rather sequester primarily IgG1 subtype antibodies. As revealed by RNA-seq and targeted quantitative PCR (qPCR, dorsal root ganglion (DRG sensory neurons harvested from either naïve or immunized mice lack enzymes (i.e., RAG1, RAG2, AID, or UNG required for generating antibody diversity and, therefore, cannot make antibodies. Additionally, transgenic mice that express a reporter fluorescent protein under the control of Igγ1 constant region fail to express Ighg1 transcripts in DRG sensory neurons. Furthermore, neural sequestration of antibodies occurs in mice rendered deficient in neuronal Rag2, but antibody sequestration is not observed in DRG sensory neurons isolated from mice that lack mature B cells [e.g., Rag1 knock out (KO or μMT mice]. Finally, adoptive transfer of Rag1-deficient bone marrow (BM into wild-type (WT mice or WT BM into Rag1 KO mice revealed that antibody sequestration was observed in DRG sensory neurons of chimeric mice with WT BM but not with Rag1-deficient BM. Together, these results indicate that DRG sensory neurons sequester and retain antigen-specific antibodies released by antibody-secreting plasma cells. Coupling this work with previous studies implicating DRG sensory neurons in regulating antigen trafficking during immunization raises the interesting possibility that the nervous system collaborates with the immune system to regulate antigen-mediated responses.

  9. Limbic encephalitis associated with anti-NH2-terminal of α-enolase antibodies

    Science.gov (United States)

    Kishitani, Toru; Matsunaga, Akiko; Ikawa, Masamichi; Hayashi, Kouji; Yamamura, Osamu; Hamano, Tadanori; Watanabe, Osamu; Tanaka, Keiko; Nakamoto, Yasunari; Yoneda, Makoto

    2017-01-01

    Abstract Several types of autoantibodies have been reported in autoimmune limbic encephalitis (LE), such as antibodies against the voltage-gated potassium channel (VGKC) complex including leucine-rich glioma inactivated 1 (LGI1). We recently reported a patient with autoimmune LE and serum anti-NH2-terminal of α-enolase (NAE) antibodies, a specific diagnostic marker for Hashimoto encephalopathy (HE), who was diagnosed with HE based on the presence of antithyroid antibodies and responsiveness to immunotherapy. This case suggests that LE patients with antibodies to both the thyroid and NAE could be diagnosed with HE and respond to immunotherapy. The aim of this study was to clarify the clinicoimmunological features and efficacy of immunotherapy in LE associated with anti-NAE antibodies to determine whether the LE is a clinical subtype of HE. We examined serum anti-NAE antibodies in 78 LE patients with limbic abnormality on magnetic resonance imaging and suspected HE based on positivity for antithyroid antibodies. Nineteen of the 78 patients had anti-NAE antibodies; however, 5 were excluded because they were double positive for antibodies to the VGKC complex including LGI1. No antibodies against the N-methyl-D-aspartate receptor (NMDAR), contactin-associated protein 2 (Caspr2), γ-aminobutyric acid-B receptor (GABABR), or α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) were detected in the 19 patients. Among the remaining 14 who were positive only for anti-NAE antibodies, the median age was 62.5 (20–83) years, 9 (64%) were women, and 8 (57%) showed acute onset, with less than 2 weeks between onset and admission. Consciousness disturbance (71%) and memory disturbance (64%) were frequently observed, followed by psychiatric symptoms (50%) and seizures (43%). The frequency of these symptoms significantly differed between the acute- and subacute-onset groups. Abnormalities in cerebrospinal fluid and electroencephalogram were commonly observed (92

  10. Childhood-onset obsessive-compulsive disorder: a tic-related subtype of OCD?

    Science.gov (United States)

    Eichstedt, J A; Arnold, S L

    2001-02-01

    Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by recurrent obsessions or compulsions that cause significant impairment or distress. Although OCD was once perceived to be relatively rare in childhood, current estimates suggest that as many as half of all adult OCD cases may have their onset in childhood or adolescence. In general, there appears to be a great deal of continuity between the clinical presentation of OCD in children and that in adults. Yet, numerous differences have also been found between child and adult OCD, including differences in sex distribution, patterns of comorbidity, and degree of familial loading. These differences raise the issue of whether obsessive-compulsive symptoms that have their onset in childhood, but perhaps persist into adult life, are meaningfully different from those that emerge de novo in adulthood. In this article, current research on child- and adult-onset OCD is critically reviewed. It is proposed that child-onset OCD represents a phenomenologically and etiologically distinct subtype of OCD, bearing a close genetic relationship to tic-disorders and possibly sharing a common or similar pathogenesis. Clinical implications of the child- versus adult-onset OCD distinction are discussed.

  11. Human antibodies to immunoglobulin A (IgA)

    International Nuclear Information System (INIS)

    Munster, P.J.J. van; Nadorp, J.H.S.M.; Shuurman, H.J.

    1978-01-01

    In the sera of 12 out of 27 individuals with IgA deficiency (serum level below 0.02 mg IgA/m) class-specific anti-IgA antibodies were demonstrated by haemagglutination. These sera showed false-positive results in a solid-phase inhibition radioimmunoassay (RIST) (apparent IgA concentration between 0.6 and 13.7 μg IgA/ml) indicating that the RIST is not an appropriate test for the analysis of serum of IgA seficient individuals. A modification of the RIST is proposed (titration RIA) that permits differentiation between low levels of IgA and class-specific anti-IgA antibodies. With this test IgA deficient individuals could be classified as those with low but detectable levels of IgA and those with class-specific anti-IgA antibodies. A computer procedure was developed to calculate both the amount and the avidity (K) of the anti-IgA antibodies and to simulate the assay system. The K value calculated from experimental points proved to be an overestimation of the K value which fitted most adequately in the simulation. The comparison of the results with clinical findings indicated a possible correlation between the amount and the avidity of the anti-IgA antibodies and the appearence of anaphylactic reactions after transfusion of IgA. (Auth.)

  12. Molecular and Therapeutic Characterization of Anti-ectodysplasin A Receptor (EDAR) Agonist Monoclonal Antibodies*

    Science.gov (United States)

    Kowalczyk, Christine; Dunkel, Nathalie; Willen, Laure; Casal, Margret L.; Mauldin, Elizabeth A.; Gaide, Olivier; Tardivel, Aubry; Badic, Giovanna; Etter, Anne-Lise; Favre, Manuel; Jefferson, Douglas M.; Headon, Denis J.; Demotz, Stéphane; Schneider, Pascal

    2011-01-01

    The TNF family ligand ectodysplasin A (EDA) and its receptor EDAR are required for proper development of skin appendages such as hair, teeth, and eccrine sweat glands. Loss of function mutations in the Eda gene cause X-linked hypohidrotic ectodermal dysplasia (XLHED), a condition that can be ameliorated in mice and dogs by timely administration of recombinant EDA. In this study, several agonist anti-EDAR monoclonal antibodies were generated that cross-react with the extracellular domains of human, dog, rat, mouse, and chicken EDAR. Their half-life in adult mice was about 11 days. They induced tail hair and sweat gland formation when administered to newborn EDA-deficient Tabby mice, with an EC50 of 0.1 to 0.7 mg/kg. Divalency was necessary and sufficient for this therapeutic activity. Only some antibodies were also agonists in an in vitro surrogate activity assay based on the activation of the apoptotic Fas pathway. Activity in this assay correlated with small dissociation constants. When administered in utero in mice or at birth in dogs, agonist antibodies reverted several ectodermal dysplasia features, including tooth morphology. These antibodies are therefore predicted to efficiently trigger EDAR signaling in many vertebrate species and will be particularly suited for long term treatments. PMID:21730053

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

    Science.gov (United States)

    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.

  14. Hyperparathyroidism and complications associated with vitamin D deficiency in HIV-infected adults in New York City, New York.

    Science.gov (United States)

    Kwan, Candice K; Eckhardt, Benjamin; Baghdadi, Jonathan; Aberg, Judith A

    2012-09-01

    Although recent studies report a high prevalence of vitamin D deficiency in HIV-infected adults similar to that in the general population, metabolic complications of vitamin D deficiency may be worsened with HIV infection and remain insufficiently characterized. We conducted a retrospective cross-sectional cohort study to determine prevalence and correlates of vitamin D deficiency and hyperparathyroidism among HIV-infected patients attending an urban clinic. Vitamin D deficiency was defined as 25(OH)-vitamin D hyperparathyroidism as parathyroid-hormone >65 pg/ml. We used the X(2) test to compare proportions and logistic regression to assess for associations. Among 463 HIV-infected patients, the prevalence of vitamin D deficiency was 59%. The prevalence of hyperparathyroidism was 30% among patients with vitamin D deficiency, 23% among those with insufficiency, and 12% among those with sufficient vitamin D levels. Vitamin D deficiency was associated with increased odds of hyperparathyroidism. Severe vitamin D deficiency was associated with elevated alkaline phosphatase, a marker for increased bone turnover. Although efavirenz use was associated with vitamin D deficiency, and protease inhibitor use with decreased odds of vitamin D deficiency, there was no statistical difference in rates of hyperparathyroidism stratified by combination antiretroviral therapy (cART) use. Given the increased risk of osteopenia with HIV infection and cART use, vitamin D supplementation for all HIV-infected patients on cART should be prescribed in accordance with the 2011 Endocrine Society guidelines. In HIV-infected patients with severe vitamin D deficiency or hyperparathyroidism, screening for osteomalacia and osteopenia may be warranted.

  15. Transaldolase deficiency in a two-year-old boy with cirrhosis

    NARCIS (Netherlands)

    Wamelink, M.M.; Struijs, E.A.; Salomons, G.S.; Fowler, D.; Jakobs, C.A.J.M.; Clayton, P.T.

    2008-01-01

    Transaldolase (TALDO) deficiency is a rare inborn error of the pentose phosphate pathway. We report the clinical presentation and laboratory findings of a new patient with TALDO deficiency. The two-year-old Arabic boy presented with neonatal onset of anemia and thrombocytopenia, tubulopathy, and

  16. Holocarboxylase synthetase deficiency pre and post newborn screening

    Directory of Open Access Journals (Sweden)

    Taraka R. Donti

    2016-06-01

    Full Text Available Holocarboxylase synthetase deficiency is an autosomal recessive disorder of biotin metabolism resulting in multiple carboxylase deficiency. The typical presentation described in the medical literature is of neonatal onset within hours to weeks of birth with emesis, hypotonia, lethargy, seizures, metabolic ketolactic acidosis, hyperammonemia, developmental delay, skin rash and alopecia. The condition is screened for by newborn screening (NBS tandem mass spectroscopy by elevated hydroxypentanoylcarnitine on dried blood spots. Urine organic acid profile may demonstrate elevated lactic, 3-OH isovaleric, 3-OH propionic, 3-MCC, methylcitric acids, and tiglylglycine consistent with loss of function of the above carboxylases. Here we describe a cohort of patients, 2 diagnosed pre-NBS and 3 post-NBS with broad differences in initial presentation and phenotype. In addition, prior to the advent of NBS, there are isolated reports of late-onset holocarboxylase synthetase deficiency in the medical literature, which describe patients diagnosed between 1 and 8 years of life, however to our knowledge there are no reports of late-onset HCLS being missed by NBS. Also we report two cases, each with novel pathogenic variants HCLS, diagnosed at age 3 years and 21 months respectively. The first patient had a normal newborn screen whilst the second had an abnormal newborn screen but was misdiagnosed as 3-methylcrotonylcarboxylase (3-MCC deficiency and subsequently lost to follow-up until they presented again with severe metabolic acidosis.

  17. Clinical presentation of anti-N-methyl-d-aspartate receptor and anti-voltage-gated potassium channel complex antibodies in children: A series of 24 cases.

    Science.gov (United States)

    Konuskan, Bahadir; Yildirim, Mirac; Topaloglu, Haluk; Erol, Ilknur; Oztoprak, Ulkuhan; Tan, Huseyin; Gocmen, Rahsan; Anlar, Banu

    2018-01-01

    The symptomatology and paraclinical findings of antibody-mediated encephalitis, a relatively novel disorder, are still being characterized in adults and children. A high index of suspicion is needed in order to identify these cases among children presenting with various neurological symptoms. The aim of this study is to examine the clinical, demographic and laboratory findings and outcome of children with anti-NMDAR and anti-VGKC encephalitis for any typical or distinctive features. Cases diagnosed with anti-N-Methyl d-aspartate receptor (NMDAR) and anti-voltage gated potassium channel (VGKC) antibody-mediated encephalopathy in four major child neurology centers are described. In four years, 16 children with NMDAR and 8 children with VGKC antibody-associated disease were identified in the participating centers. The most frequent initial manifestation consisted of generalized seizures and cognitive symptoms in both groups. Movement abnormalities were frequent in anti-NMDAR patients and autonomic symptoms, in anti-VGKC patients. Cerebrospinal fluid (CSF) protein, cell count and IgG index were normal in 9/15 anti-NMDAR and 5/8 anti-VGKC patients tested. EEG and MRI findings were usually nonspecific and non-contributory. The rate and time of recovery was not related to age, sex, acute or subacute onset, antibody type, MRI, EEG or CSF results. Treatment within 3 months of onset was associated with normal neurological outcome. Our results suggest anti-NMDAR and VGKC encephalopathies mostly present with non-focal neurological symptoms longer than 3 weeks. In contrast with adult cases, routine CSF testing, MRI and EEG did not contribute to the diagnosis in this series. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  18. Anemia and hematinic deficiencies in gastric parietal cell antibody-positive and antibody-negative erosive oral lichen planus patients with thyroid antibody positivity

    Directory of Open Access Journals (Sweden)

    Julia Y.-F. Chang

    2016-11-01

    Conclusion: We conclude that serum GPCA is the major factor causing vitamin B12 deficiency, macrocytosis and pernicious anemia in GPCA+/TGA/TMA/EOLP patients. ELOP itself but not TGA/TMA positivity plays a significant role in causing anemia and hematinic deficiencies in GPCA−/TGA/TMA/EOLP patients.

  19. Sensorimotor oscillations prior to speech onset reflect altered motor networks in adults who stutter

    Directory of Open Access Journals (Sweden)

    Anna-Maria Mersov

    2016-09-01

    Full Text Available 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 twelve 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 (15-25Hz 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.

  20. Feasibility of teaching motivational interviewing to parents of young adults with recent-onset schizophrenia and co-occurring cannabis use

    NARCIS (Netherlands)

    Smeerdijk, Maarten; Keet, René; de Haan, Lieuwe; Barrowclough, Christine; Linszen, Don; Schippers, Gerard

    2014-01-01

    This study examined the feasibility of providing motivational interviewing (MI) training to parents of young adults with recent-onset schizophrenia and co-occurring cannabis use. The training was offered in a mental health care setting as part of a family motivational intervention (FMI).

  1. Living with transversal upper limb reduction deficiency: limitations experienced by young adults during their transition to adulthood.

    Science.gov (United States)

    Lankhorst, Ilse M F; Baars, Erwin C T; Wijk, Iris van; Janssen, Wim G M; Poelma, Margriet J; van der Sluis, Corry K

    2017-08-01

    During transition to adulthood young adults with disabilities are at risk of experiencing limitations due to changing physical and social requirements. To determine whether young adults with transversal upper limb reduction deficiency (tULRD) have experienced limitations in various domains of participation during transition to adulthood and how they dealt with these limitations. Fifteen participants (mean age 21.4 years) with tULRD. A qualitative study was performed using a semi-structured interview based on the Rotterdam Transition Profile to identify the limitations experienced in participation domains. Almost all the participants reported difficulties in finding a suitable study or job. Most young adults were convinced they were suitable for almost any study or job, but their teachers and potential employers were more reserved. Few difficulties were reported on the domains leisure activities, intimate relationships/sexuality, housing/housekeeping and transportation. Participants preferred to develop their own strategies for dealing with limitations. Various aids, adaptations and prostheses were used to overcome limitations. Rehabilitation teams were infrequently consulted for advice in solving transitional problems. Young adults with tULRD experience limitations mainly in choosing and finding a suitable study or job. Rehabilitation teams may play a more extensive role in supporting individuals with transitional problems. Implications for rehabilitation Most young adults with transversal upper limb reduction deficiency (tULRD) experience limitations in study and job selection during transition to adulthood, but they do not consult the rehabilitation team. Assessment of abilities in relation to job interests and practicing job specific bimanual activities may be helpful for young adults with a tULRD. How the rehabilitation teams can meet the needs of young adults with tULRD during transitional phases, when autonomy is of growing importance, should be investigated

  2. Effects of body weight on antibody titers against canine parvovirus type 2, canine distemper virus, and canine adenovirus type 1 in vaccinated domestic adult dogs.

    Science.gov (United States)

    Taguchi, Masayuki; Namikawa, Kazuhiko; Maruo, Takuya; Saito, Miyoko; Lynch, Jonathan; Sahara, Hiroeki

    2012-10-01

    The objective of this study was to determine whether post-vaccination antibody titers vary according to body weight in adult dogs. Antibody titers against canine parvovirus type 2 (CPV-2), canine distemper virus (CDV), and canine adenovirus type 1 (CAdV-1) were measured for 978 domestic adult dogs from 2 to 6 y of age. The dogs had been vaccinated approximately 12 mo earlier with a commercial combination vaccine. The dogs were divided into groups according to their weight. It was found that mean antibody titers in all weight groups were sufficient to prevent infection. Intergroup comparison, however, revealed that CPV-2 antibody titers were significantly higher in the Super Light ( 20 kg) groups and were also significantly higher in the Light (5 to 9.9 kg) group than in the Heavy group. Antibody titers against CDV were significantly higher in the Super Light, Light, and Medium groups than in the Heavy group. There were no significant differences among the groups for the CAdV-1 antibody titers.

  3. Latent autoimmune diabetes of adults: From oral hypoglycemic agents to early insulin

    Directory of Open Access Journals (Sweden)

    Resham R Poudel

    2012-01-01

    Full Text Available Approximately 10% of phenotypic type 2 diabetics have islet autoantibodies and are referred to as having latent autoimmune diabetes of adults (LADA, and they land on early sulfonylurea failure and require insulin. Diagnosing LADA has treatment implications because of high risk of progression to insulin dependency. But often there is delay in insulin therapy, as there are no recommendations for islet antibody testing in adult-onset diabetes currently. LADA clinical risk score can identify adults at high risk who may benefit from antibody testing. The optimal treatment of LADA is not established. Early insulin therapy helps to achieve good metabolic control and better long-term outcomes by preserving b-cells and endogenous C-peptide secretion. Sulfonylureas are better avoided as they exhaust b-cells; glitazones and exenatide have favorable outcomes, whereas metformin needs to be used with caution. Understanding LADA will also bring new windows in managing type 1 diabetes. Information acquisition was done by reviewing the medical literature published since 1987, with particular attention to the natural history, genetic factors, and treatment of LADA.

  4. Childhood Onset Schizophrenia: Clinical Features, Course and Outcome

    Science.gov (United States)

    Sood, Mamta; Kattimani, Shivanand

    2008-01-01

    Schizophrenia in children is diagnosed by using adult criteria. Based on the age of onset, patients with childhood onset schizophrenia (COS) are subdivided into those with very early onset (before age 12-14 years) and those with early onset (between 14-17 years). The prevalence of COS is reported to be 1 in 10,000 before the age of 12 years;…

  5. Adult onset asthma and interaction between genes and active tobacco smoking: The GABRIEL consortium.

    Directory of Open Access Journals (Sweden)

    J M Vonk

    Full Text Available Genome-wide association studies have identified novel genetic associations for asthma, but without taking into account the role of active tobacco smoking. This study aimed to identify novel genes that interact with ever active tobacco smoking in adult onset asthma.We performed a genome-wide interaction analysis in six studies participating in the GABRIEL consortium following two meta-analyses approaches based on 1 the overall interaction effect and 2 the genetic effect in subjects with and without smoking exposure. We performed a discovery meta-analysis including 4,057 subjects of European descent and replicated our findings in an independent cohort (LifeLines Cohort Study, including 12,475 subjects.First approach: 50 SNPs were selected based on an overall interaction effect at p<10-4. The most pronounced interaction effect was observed for rs9969775 on chromosome 9 (discovery meta-analysis: ORint = 0.50, p = 7.63*10-5, replication: ORint = 0.65, p = 0.02. Second approach: 35 SNPs were selected based on the overall genetic effect in exposed subjects (p <10-4. The most pronounced genetic effect was observed for rs5011804 on chromosome 12 (discovery meta-analysis ORint = 1.50, p = 1.21*10-4; replication: ORint = 1.40, p = 0.03.Using two genome-wide interaction approaches, we identified novel polymorphisms in non-annotated intergenic regions on chromosomes 9 and 12, that showed suggestive evidence for interaction with active tobacco smoking in the onset of adult asthma.

  6. High incidence of antibodies to HTLV-I tax in blood relatives of adult T cell leukemia patients.

    Science.gov (United States)

    Okayama, A; Chen, Y M; Tachibana, N; Shioiri, S; Lee, T H; Tsuda, K; Essex, M

    1991-01-01

    Adult T cell leukemia (ATL) is caused by the human T cell leukemia virus type I (HTLV-I). Although the mechanisms of the leukemogenic process are unknown, the tax gene may have a role in this process. Because clustering occurs with HTLV-I and ATL, members of ATL families were examined for antibodies to the tax protein and compared with matched HTLV-I-positive blood donors. To investigate the antibody response to this protein, a plasmid, pBHX-4, was constructed to express a recombinant tax protein (r-tax). For ATL patients and their HTLV-I antibody-positive blood relatives, the rate of seroreactivity with the r-tax protein was 67.3% (35/52), compared with 51.6% (97/188) for HTLV-I antibody-positive control blood donors (P less than .05). The difference between direct offspring of ATL patients and matched HTLV-I blood donors was even greater (84.2% [16/91] vs. 44.2% [42/95]; P less than .005). Thus, tax antibody positivity in direct offspring of ATL patients may reflect differences in time or route of HTLV-I infection. Alternatively, it might reflect genetic differences in host susceptibility or virus strain.

  7. Frequency and significance of antibodies to liver/kidney microsome type 1 in adults with chronic active hepatitis.

    Science.gov (United States)

    Czaja, A J; Manns, M P; Homburger, H A

    1992-10-01

    To assess the frequency of antibodies to liver/kidney microsome type 1 (anti-LKM1) in patients with chronic active hepatitis, 131 such patients were tested by an indirect immunofluorescence assay. Of 62 patients with type 1 autoimmune hepatitis, none were seropositive. In contrast, 3 of 11 patients with autoimmune hepatitis and antimitochondrial antibodies (27%) were seropositive for anti-LKM1. Each had responded to corticosteroid therapy, and retesting of sera confirmed that each had been misclassified as antimitochondrial antibody positive. None of the patients with chronic active hepatitis B (14 patients) or C (24 patients) had anti-LKM1. Similarly, none of the 20 patients with cryptogenic disease had these antibodies. It is concluded that anti-LKM1 is specific for type 2 autoimmune hepatitis and is infrequent in adult patients seen at a referral center in the United States for chronic active hepatitis. Anti-LKM1 reactivity may be misinterpreted as antimitochondrial antibody reactivity by indirect immunofluorescence. Chronic hepatitis B and C virus infections are not important stimuli for the production of anti-LKM1, and testing for anti-LKM 1 is unlikely to clarify the nature of cryptogenic disease.

  8. Molecular and clinical characterization of a series of patients with childhood-onset lysosomal acid lipase deficiency. Retrospective investigations, follow-up and detection of two novel LIPA pathogenic variants.

    Science.gov (United States)

    Pisciotta, Livia; Tozzi, Giulia; Travaglini, Lorena; Taurisano, Roberta; Lucchi, Tiziano; Indolfi, Giuseppe; Papadia, Francesco; Di Rocco, Maja; D'Antiga, Lorenzo; Crock, Patricia; Vora, Komal; Nightingale, Scott; Michelakakis, Helen; Garoufi, Anastasia; Lykopoulou, Lilia; Bertolini, Stefano; Calandra, Sebastiano

    2017-10-01

    Childhood/Adult-onset Lysosomal Acid Lipase Deficiency (LAL-D) is a recessive disorder due to loss of function variants of LAL, the enzyme which hydrolyses cholesteryl esters, derived from internalized apoB containing lipoproteins. The disease is characterized by multi-organ involvement including the liver, spleen, intestine and cardiovascular system. The aim of this study was the clinical and molecular characterization of 14 (13 unrelated) previously unreported patients with childhood-onset LAL-D. Data collected included clinical and laboratory investigations, liver imaging, liver biopsy and LIPA gene analysis. The response to lipid-lowering medications, liver transplantation and enzyme replacement therapy (ERT) was reported for some patients. LAL-D was suspected at 4.4 ± 3.3 years of age for the presence of hepatomegaly, elevated serum transaminases and hypercholesterolemia, and was confirmed by liver biopsy/imaging and LAL assay. The follow up period ranged from 3 to 40 years (mean 7.8 ± 4.0 years in 13 cases). Patients treated with statins with or without ezetimibe showed 28% reduction of plasma LDL-cholesterol without a tangible effect on liver enzymes; some patients receiving ERT showed normalized lipoprotein profile and transaminase levels. The common c.894G > A variant was observed in homozygosity or compound heterozygosity in 10 patients. We found seven previously reported variants: p.(Trp140*), p.(Arg218*), p.(Gly266*), p.(Thr288Ile), p.(Leu294Ser), p.(His295Tyr) and p.(Gly342Arg) and two novel variants: p.(Asp345Asn), affecting the LAL catalytic triad, and c.229+3A > C, affecting splicing. Homozygosity for p.(Thr288Ile) or c.229+3A > C was associated with a severe phenotype. This study provides additional data on the features of childhood-onset LAL-D and describes two novel pathogenic variants of the LIPA gene. Copyright © 2017. Published by Elsevier B.V.

  9. Impact of a Plasmodium falciparum AMA1 vaccine on antibody responses in adult Malians.

    Directory of Open Access Journals (Sweden)

    Alassane Dicko

    2007-10-01

    Full Text Available Apical Membrane Antigen 1 (AMA1 of Plasmodium falciparum merozoites is a leading blood-stage malaria vaccine candidate. Protection of Aotus monkeys after vaccination with AMA1 correlates with antibody responses.A randomized, controlled, double-blind phase 1 clinical trial was conducted in 54 healthy Malian adults living in an area of intense seasonal malaria transmission to assess the safety and immunogenicity of the AMA1-C1 malaria vaccine. AMA1-C1 contains an equal mixture of yeast-expressed recombinant proteins based on sequences from the FVO and 3D7 clones of P. falciparum, adsorbed on Alhydrogel. The control vaccine was the hepatitis B vaccine (Recombivax. Participants were enrolled into 1 of 3 dose cohorts (n = 18 per cohort and randomized 2:1 to receive either AMA1-C1 or Recombivax. Participants in the first, second, and third cohorts randomized to receive AMA1-C1 were vaccinated with 5, 20 and 80 microg of AMA1-C1, respectively. Vaccinations were administered on days 0, 28, and 360, and participants were followed until 6 months after the final vaccination. AMA1-C1 was well tolerated; no vaccine-related severe or serious adverse events were observed. AMA1 antibody responses to the 80 microg dose increased rapidly from baseline levels by days 14 and 28 after the first vaccination and continued to increase after the second vaccination. After a peak 14 days following the second vaccination, antibody levels decreased to baseline levels one year later at the time of the third vaccination that induced little or no increase in antibody levels.Although the AMA1-C1 vaccine candidate was well-tolerated and induced antibody responses to both vaccine and non-vaccine alleles, the antibody response after a third dose given at one year was lower than the response to the initial vaccinations. Additionally, post-vaccination increases in anti-AMA1 antibody levels were not associated with significant changes in in vitro growth inhibition of P. falciparum

  10. Adult-onset photosensitivity: clinical significance and epilepsy syndromes including idiopathic (possibly genetic) photosensitive occipital epilepsy.

    Science.gov (United States)

    Koutroumanidis, Michalis; Tsirka, Vasiliki; Panayiotopoulos, Chrysostomos

    2015-09-01

    To evaluate the clinical associations of adult-onset photosensitivity, we studied the clinical and EEG data of patients who were referred due to a possible first seizure and who had a photoparoxysmal response on their EEG. Patients with clinical evidence of photosensitivity before the age of 20 were excluded. Of a total of 30 patients, four had acute symptomatic seizures, two had vasovagal syncope, and 24 were diagnosed with epilepsy. Nine of the 24 patients had idiopathic (genetic) generalized epilepsies and predominantly generalized photoparoxysmal response, but also rare photically-induced seizures, while 15 had exclusively, or almost exclusively, reflex photically-induced occipital seizures with frequent secondary generalization and posterior photoparoxysmal response. Other important differences included a significantly older age at seizure onset and paucity of spontaneous interictal epileptic discharges in patients with photically-induced occipital seizures; only a quarter of these had occasional occipital spikes, in contrast to the idiopathic (genetic) generalized epilepsy patients with typically generalized epileptic discharges. On the other hand, both groups shared a positive family history of epilepsy, common seizure threshold modulators (such as tiredness and sleep deprivation), normal neurological examination and MRI, a generally benign course, and good response to valproic acid. We demonstrated that photosensitivity can first occur in adult life and manifest, either as idiopathic (possibly genetic) photosensitive occipital epilepsy with secondary generalization or as an EEG, and less often, a clinical/EEG feature of idiopathic (genetic) generalized epilepsies. Identification of idiopathic photosensitive occipital epilepsy fills a diagnostic gap in adult first-seizure epileptology and is clinically important because of its good response to antiepileptic drug treatment and fair prognosis.

  11. Prevalence and Correlates of Vitamin D Deficiency and Insufficiency in Luxembourg Adults: Evidence from the Observation of Cardiovascular Risk Factors (ORISCAV-LUX Study

    Directory of Open Access Journals (Sweden)

    Ala'a Alkerwi

    2015-08-01

    Full Text Available Evidence on vitamin D status and related risk factors in Luxembourg adults is lacking. This study aimed to determine the prevalence of vitamin D deficiency and insufficiency and related risk factors among healthy adults in Luxembourg. Based on clinicians’ observations, it was hypothesized that vitamin D deficiency and insufficiency might be common in our population, constituting a significant public health concern. A nationally representative random sample of 1432 adults was enrolled in the ORISCAV-LUX study, 2007–2008. The participants were divided into four categories according to their serum concentrations of 25-hydroxyvitamin D [25(OHD]. Descriptive, univariate and multivariate statistical analyses used weighted methods to account for the stratified sampling scheme. Only 17.1% of the population had a “desirable” serum 25(OHD level ≥75 nmol/L, whereas 27.1% had “inadequate” [serum 25(OHD level 50–74 nmol/L], 40.4% had “insufficient” [serum 25(OHD level 25–49 nmol/L], and 15.5% had “deficient” [serum 25(OHD level <25 nmol/L]. The prevalence of vitamin D deficiency was greater among current smokers, obese subjects, those having reduced HDL-cholesterol level and fair/poor self-perception of health, compared to their counterparts. The prevalence of vitamin D insufficiency was additionally higher among nondrinkers of alcohol, Portuguese and subjects from non-European countries. The final multivariate logistic regression analyses revealed that smoking status and obesity were independent correlates of vitamin D deficiency and insufficiency, respectively. Inadequate vitamin D status is highly prevalent among adults in Luxembourg and is associated with specific lifestyle factors. Along with the effect of vitamin D deficiency and insufficiency on the risk of several diseases, cancer and mortality, our findings have practical implications for public health dietary recommendations, and of particular importance for healthcare

  12. Early- versus Late-Onset Systemic Sclerosis

    Science.gov (United States)

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

    2014-01-01

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

  13. Small for Gestational Age and Magnesium: Intrauterine magnesium deficiency may induce metabolic syndrome in later life

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    Junji Takaya

    2015-12-01

    Full Text Available Magnesium deficiency during pregnancy as a result of insufficient or low intake of magnesium is common in developing and developed countries. Previous reports have shown that intracellular magnesium of cord blood platelets is lower among small for gestational age (SGA groups than that of appropriate for gestational age (AGA groups, suggesting that intrauterine magnesium deficiency may result in SGA. Additionally, the risk of adult-onset diseases such as insulin resistance syndrome is greater among children whose mothers were malnourished during pregnancy, and who consequently had a low birth weight. In a number of animal models, poor nutrition during pregnancy leads to offspring that exhibit pathophysiological changes similar to human diseases. The offspring of pregnant rats fed a magensium restricted diet have developed hypermethylation in the hepatic 11β-hydroxysteroid dehydrogenase-2 promoter. These findings indicate that maternal magnesium deficiencies during pregnancy influence regulation of non-imprinted genes by altering the epigenetic regulation of gene expression, thereby inducing different metabolic phenotypes. Magnesium deficiency during pregnancy may be responsible for not only maternal and fetal nutritional problems, but also lifelong consequences that affect the offspring throughout their life. Epidemiological, clinical, and basic research on the effects of magnesium deficiency now indicates underlying mechanisms, especially epigenetic processes.

  14. Developmental programming of vascular dysfunction by prenatal and postnatal zinc deficiency in male and female rats.

    Science.gov (United States)

    Mendes Garrido Abregú, Facundo; Gobetto, María Natalia; Juriol, Lorena Vanesa; Caniffi, Carolina; Elesgaray, Rosana; Tomat, Analía Lorena; Arranz, Cristina

    2018-06-01

    Micronutrient malnutrition during intrauterine and postnatal growth may program cardiovascular diseases in adulthood. We examined whether moderate zinc restriction in male and female rats throughout fetal life, lactation and/or postweaning growth induces alterations that can predispose to the onset of vascular dysfunction in adulthood. Female Wistar rats were fed low- or control zinc diets from pregnancy to offspring weaning. After weaning, offspring were fed either a low- or a control zinc diet until 81 days. We evaluated systolic blood pressure (SBP), thoracic aorta morphology, nitric oxide (NO) system and vascular reactivity in 6- and/or 81-day-old offspring. At day 6, zinc-deficient male and female offspring showed a decrease in aortic NO synthase (NOS) activity accompanied by an increase in oxidative stress. Zinc-deficient 81-day-old male rats exhibited an increase in collagen deposition in tunica media, as well as lower activity of endothelial NOS (eNOS) that could not be reversed with an adequate zinc diet during postweaning life. Zinc deficiency programmed a reduction in eNOS protein expression and higher SBP only in males. Adult zinc-deficient rats of both sexes showed reduced vasodilator response dependent on eNOS activity and impaired aortic vasoconstrictor response to angiotensin-II associated with alterations in intracellular calcium mobilization. Female rats were less sensitive to the effects of zinc deficiency and exhibited higher eNOS activity and/or expression than males, without alterations in SBP or aortic histology. This work strengthens the importance of a balanced intake of micronutrients during perinatal growth to ensure adequate vascular function in adult life. Copyright © 2018 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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.

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... increased need for iron during growth spurts. Older adults, especially those over age ... athletes. Athletes, especially young females, are at risk for iron deficiency. Endurance ...

  17. Glucose-6-Phosphate Dehydrogenase Deficiency and Adrenal Hemorrhage in a Filipino Neonate with Hyperbilirubinemia

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    Akira Ohishi

    2013-05-01

    Full Text Available We report on a Filipino neonate with early onset and prolonged hyperbilirubinemia who was delivered by a vacuum extraction due to a prolonged labor. Subsequent studies revealed adrenal hemorrhage and glucose-6-phosphate dehydrogenase (G6PD deficiency. It is likely that asphyxia and resultant hypoxia underlie the occurrence of adrenal hemorrhage and the clinical manifestation of G6PD deficiency and that the presence of the two events explains the early onset and prolonged hyperbilirubinemia of this neonate. Our results represent the importance of examining possible underlying factors for the development of severe, early onset, or prolonged hyperbilirubinemia.

  18. Comparative anti-androgenic actions of vinclozolin and flutamide on transgenerational adult onset disease and spermatogenesis

    OpenAIRE

    Anway, Matthew D.; Rekow, Stephen S.; Skinner, Michael K.

    2008-01-01

    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 i...

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

    Science.gov (United States)

    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.

  20. Vitamin D Deficiency in Adult Patients with Schizophreniform and Autism Spectrum Syndromes: A One-Year Cohort Study at a German Tertiary Care Hospital

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    Dominique Endres

    2016-10-01

    Full Text Available Introduction: Vitamin D has many immunomodulatory, anti-inflammatory, and neuroprotective functions, and previous studies have demonstrated an association between vitamin D deficiency and neuropsychiatric disease. The aim of our study was to analyze the prevalence of vitamin D deficiency in a one-year cohort of adult inpatients with schizophreniform and autism-spectrum syndromes in a naturalistic in-patient setting in Germany. Participants and methods: Our study was comprised of 60 adult schizophreniform and 23 adult high-functioning autism spectrum patients who were hospitalized Page: 2between January and December of 2015. We compared our findings with a historical German reference cohort of 3,917 adults using Pearson’s two-sided chi-squared test. The laboratory measurements of 25-hydroxyvitamin D2/3 (25(OHvitamin D were obtained using a chemiluminescence immunoassay. Results: In the schizophreniform group, we found decreased ( 30 ng/ml were observed in only 5% of the schizophreniform patients, 8.7% of the autism spectrum patients, and 21.9% of the healthy controls. Discussion: We found very high rates of 25(OHvitamin D deficiency in both patient groups, and have discussed whether our findings might be related to alterations in the immunological mechanisms. Irrespective of the possible pathophysiological links between vitamin D deficiency and schizophrenia or autism spectrum disorders, a more frequent measurement of vitamin D levels seems to be justified in these patient groups. Further prospective, controlled, blinded, and randomized research should be conducted to analyze the effectiveness of vitamin D supplementation on the improvement of psychiatric symptoms.

  1. Prevalence of serum celiac antibodies in a multiracial Asian population--a first study in the young Asian adult population of Malaysia.

    Science.gov (United States)

    Yap, Theresa Wan-Chen; Chan, Weng-Kai; Leow, Alex Hwong-Ruey; Azmi, Ahmad Najib; Loke, Mun-Fai; Vadivelu, Jamuna; Goh, Khean-Lee

    2015-01-01

    Celiac disease (CD) is an immune-mediated disorder induced by the ingestion of gluten in genetically susceptible persons. The prevalence of CD in Malaysia is unknown. We aim to determine the seroprevalence of CD antibodies and also investigate the correlation between H. pylori infection and CD in the young and healthy multiracial Malaysian population. Healthy young adult volunteers between the ages of 18-30 years were consecutively recruited from June 2012 to May 2014 at the University of Malaya Medical Centre (UMMC), Kuala Lumpur. Serum samples from all the participants were tested for anti-gliadin antibody immunoglobulin A/immunoglobulin G (IgA/IgG) and anti-tissue transglutaminase antibody (tTG) IgA/IgG. Samples positive for both anti-gliadin and anti-tTG were further validated for anti-human endomysial IgA antibodies (EmA). Serological diagnosis of CD was made when anti-gliadin, anti-tTG and anti-EmA were positive. 562 qualified participants with mean age 24 ± 2.4 years old were recruited into our study. CD was found in 7 participants where most of them were asymptomatic and unaware of their CD status. The median of anti-gliadin and anti-tTG IgA/IgG value was 38.2 U/ml (interquartile range, 28.3-60.4 U/ml) and 49.2 U/ml (interquartile range, 41.1-65.9 U/ml), respectively. Seroprevalence of CD antibodies was 1.9% (6 out of 324) in female while only 0.4% (1 out of 238) in male. Seroprevalence among Malay was 0.8% (2 of 236), Chinese was 1.7% (3 of 177) and Indian was 1.3% (2 of 149). Overall, seroprevalence of CD antibodies in healthy asymptomatic adults in the Malaysian population was 1.25% (95% CI, 0.78%-1.72%). No significant relationship was discovered between CD and H. pylori infection. The seroprevalence of CD antibodies in healthy young adults in the Malaysian population was 1.25% (1 in 100). CD is underdiagnosed and it could be a much greater problem in Malaysia than previously thought.

  2. Prevalence of Serum Celiac Antibodies in a Multiracial Asian Population-A First Study in the Young Asian Adult Population of Malaysia

    Science.gov (United States)

    Yap, Theresa Wan-Chen; Chan, Weng-Kai; Leow, Alex Hwong-Ruey; Azmi, Ahmad Najib; Loke, Mun-Fai; Vadivelu, Jamuna; Goh, Khean-Lee

    2015-01-01

    Background Celiac disease (CD) is an immune-mediated disorder induced by the ingestion of gluten in genetically susceptible persons. The prevalence of CD in Malaysia is unknown. We aim to determine the seroprevalence of CD antibodies and also investigate the correlation between H. pylori infection and CD in the young and healthy multiracial Malaysian population. Methods Healthy young adult volunteers between the ages of 18–30 years were consecutively recruited from June 2012 to May 2014 at the University of Malaya Medical Centre (UMMC), Kuala Lumpur. Serum samples from all the participants were tested for anti-gliadin antibody immunoglobulin A/immunoglobulin G (IgA/IgG) and anti-tissue transglutaminase antibody (tTG) IgA/IgG. Samples positive for both anti-gliadin and anti-tTG were further validated for anti-human endomysial IgA antibodies (EmA). Serological diagnosis of CD was made when anti-gliadin, anti-tTG and anti-EmA were positive. Results 562 qualified participants with mean age 24 ± 2.4 years old were recruited into our study. CD was found in 7 participants where most of them were asymptomatic and unaware of their CD status. The median of anti-gliadin and anti-tTG IgA/IgG value was 38.2 U/ml (interquartile range, 28.3–60.4 U/ml) and 49.2 U/ml (interquartile range, 41.1–65.9 U/ml), respectively. Seroprevalence of CD antibodies was 1.9% (6 out of 324) in female while only 0.4% (1 out of 238) in male. Seroprevalence among Malay was 0.8% (2 of 236), Chinese was 1.7% (3 of 177) and Indian was 1.3% (2 of 149). Overall, seroprevalence of CD antibodies in healthy asymptomatic adults in the Malaysian population was 1.25% (95% CI, 0.78%-1.72%). No significant relationship was discovered between CD and H. pylori infection. Conclusions The seroprevalence of CD antibodies in healthy young adults in the Malaysian population was 1.25% (1 in 100). CD is underdiagnosed and it could be a much greater problem in Malaysia than previously thought. PMID:25799401

  3. Clinical & immunological profile of newly diagnosed patients with youth onset diabetes mellitus

    Directory of Open Access Journals (Sweden)

    D K Dhanwal

    2014-01-01

    Interpretation & conclusions: About half of the youth onset diabetes mellitus patients from north India had presence of pancreatic autoimmunity in the form of GAD, ICA512/IA2, and insulin antibodies or a combination of antibodies suggestive of having type 1 DM. Further studies need to be done on a large sample size in different parts of the country

  4. Efficacy and safety of vitamin D3 B.O.N intramuscular injection in Korean adults with vitamin D deficiency

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    Han Seok Choi

    2016-12-01

    Conclusion: Intramuscular injection of vitamin D3 200,000 IU was superior to placebo in terms of its impact on serum 25(OHD concentrations, and is considered to be safe and effective in Korean adults with vitamin D deficiency.

  5. Genetics Home Reference: common variable immune deficiency

    Science.gov (United States)

    ... disorders are immune thrombocytopenia purpura, which is an abnormal bleeding disorder caused by a decrease in cell fragments involved ... antibodies makes it difficult for people with this disorder to fight off infections. Abnormal and deficient immune responses over time likely contribute ...

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

    Science.gov (United States)

    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.

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

    NARCIS (Netherlands)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2017-12-01

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

  9. 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.

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Péricles A. D. Duarte

    2017-01-01

    Full Text Available 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.

  11. New-Onset Refractory Status Epilepticus: More Investigations, More Questions

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    Philippe Dillien

    2016-06-01

    Full Text Available A 27-year-old previously healthy woman was admitted to the hospital with recurrent seizures. Status epilepticus developed that became refractory to third-line therapy with propofol and barbiturates. The patient had a very extensive diagnostic workup including autoimmune, viral and genetic investigations. A tentative immune therapy was proposed with high doses of steroids and plasma exchanges. Our patient had an inherited heterozygous single nucleotide variant in the sequence c.1280A>G [p.Lys427Arg] of the SMC3 gene that was insufficient to explain the seizures. Surprisingly, IgM antibodies against Japanese encephalitis virus were positive on the serum drawn 11 days after symptom onset, as detected by ELISA and the immunofluorescence antibody (IFA technique. IgG antibodies were also positive using the IFA technique, but not with ELISA. The same investigations as well as the detection of the viral genome by the q-RT-PCR technique were negative on cerebrospinal fluid. Despite the suspicion of a viral infection, we concluded that our patient had a new-onset refractory status epilepticus of cryptogenic origin. Termination of the status epilepticus was obtained after 47 days, with a possible benefit from the introduction of ketamine.

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

    Science.gov (United States)

    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, ppersonality 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.

  13. Diffusion and ADC-map images detect ongoing demyelination on subcortical white matter in an adult metachromatic leukodystrophy patient with autoimmune Hashimoto thyroiditis

    Science.gov (United States)

    Miura, Akiko; Kumabe, Yuri; Kimura, En; Yamashita, Satoshi; Ueda, Akihiko; Hirano, Teruyuki; Uchino, Makoto

    2010-01-01

    Adult-onset metachromatic leukodystrophy (MLD) often shows schizophrenia- or encephalopathy-like symptoms at an early stage, such as behavioural abnormalities, cognitive impairment, mood disorders and hallucinations. The authors report the case of an adult woman with MLD who had been given antipsychotic medication for schizophrenia. In the differential diagnosis, screening of auto-antibodies was important for ruling out other encephalopathies as she had a euthyroid Hashimoto thyroiditis. Diagnosis was based the results of MRI, nerve conduction velocity, sensory evoked potential, motor evoked potential, lysosomal enzyme activity and gene analysis studies. Brain MRI showed diffuse demyelination spreading from the deep white matter to subcortical area as high signals at the edges of these lesions in diffusion and apparent diffusion coefficient-map images with the U-fibres conserved. The authors diagnosed adult-onset MLD coexisting with euthyroid autoimmune Hashimoto thyroiditis. PMID:22798296

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

    Science.gov (United States)

    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.

  15. Chronic Giardia muris infection in anti-IgM-treated mice. I. Analysis of immunoglobulin and parasite-specific antibody in normal and immunoglobulin-deficient animals.

    Science.gov (United States)

    Snider, D P; Gordon, J; McDermott, M R; Underdown, B J

    1985-06-01

    To investigate the role of B cells and antibody in the immune response of mice to the murine intestinal parasite Giardia muris, we used mice treated from birth with rabbit anti-IgM antisera (aIgM). Such mice developed in serum and in gut secretions extreme Ig deficiency (IgM, IgA, and IgG) relative to control animals. The aIgM-treated mice showed no anti-G. muris antibody in serum or in gut wash material. Infections of G. muris in these mice were chronic, with a high load of parasite present in the small bowel, as reflected by prolonged cyst excretion (greater than 11 wk) and high trophozoite counts. In contrast, normal, untreated mice or NRS-treated animals developed anti-parasite IgA and IgG antibody in serum, demonstrated IgA antibody against the parasite in gut washings, and expelled the parasite within 9 wk. These effects of aIgM treatment on the murine response to primary infection with G. muris were demonstrated in two strains of mice: BALB/c and (C57BL/6 X C3H/He) F1. It was also observed that the response to G. muris infection in untreated animals was characterized by higher than normal total secretion of IgA into the gut and a concomitant increase in the serum polymeric IgA level. Mice treated with aIgM had a marked decrease of both monomeric and polymeric IgA in serum, and little detectable IgA in the intestinal lumen. These experiments provide the first demonstration that anti-IgM treatment suppresses a specific intestinal antibody response to antigen, and provide evidence that B cells and antibody play a role in the development of an effective response to a primary infection with G. muris in mice.

  16. Liver and Skin Histopathology in Adults with Acid Sphingomyelinase Deficiency (Niemann-Pick Disease Type B)

    OpenAIRE

    Thurberg, Beth L.; Wasserstein, Melissa P.; Schiano, Thomas; O’Brien, Fanny; Richards, Susan; Cox, Gerald F.; McGovern, Margaret M.

    2012-01-01

    Acid sphingomyelinase deficiency (ASMD) is a lysosomal storage disorder characterized by the pathologic accumulation of sphingomyelin in multiple cells types, and occurs most prominently within the liver, spleen and lungs, leading to significant clinical disease. Seventeen ASMD patients underwent a liver biopsy during baseline screening for a Phase 1 trial of recombinant human acid sphingomyelinase (rhASM) in adults with Niemann-Pick disease type B. Eleven of the 17 were enrolled in the trial...

  17. Adult onset Hallervorden-Spatz disease with psychotic symptoms.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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…

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

    Science.gov (United States)

    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.

  20. Long-Term Melatonin Therapy for Adolescents and Young Adults with Chronic Sleep Onset Insomnia and Late Melatonin Onset : Evaluation of Sleep Quality, Chronotype, and Lifestyle Factors Compared to Age-Related Randomly Selected Population Cohorts

    NARCIS (Netherlands)

    Zwart, Tom; Smits, Marcel G; Egberts, Toine C G; Rademaker, Carin M A; van Geijlswijk, Ingeborg M

    2018-01-01

    The extent of continuance of melatonin therapy initiated in pre-pubertal children with chronic sleep onset insomnia (CSOI) was investigated in young adult life. Sleep timing, sleep quality, adverse events, reasons for cessation of therapy, and patient characteristics with regard to therapy regimen,

  1. Childhood-onset systemic lupus erythematosus in Singapore: clinical phenotypes, disease activity, damage, and autoantibody profiles.

    Science.gov (United States)

    Tan, J H T; Hoh, S F; Win, M T M; Chan, Y H; Das, L; Arkachaisri, T

    2015-08-01

    Childhood-onset systemic lupus erythematosus (cSLE) is a multisystem autoimmune disease characterized by immune dysregulation affecting patients less than 18 years old. One-fifth of SLE cases are diagnosed during childhood. cSLE presents differently from adults and has a more severe and aggressive course. We describe the clinical and antibody profiles in our cSLE Singapore cohort. All cSLE patients who satisfied the 1997 American College of Rheumatology diagnostic criteria were captured in our lupus registry from January 2009 to January 2014. Data including demographic, cumulative clinical, serologic data, and damage indices were collected. Adjusted mean SLEDAI-2K (AMS) was used to summarize disease activity over multiple visits. Cluster analysis using non-hierarchical K-means procedure was performed on eight selected antibodies. The 64 patients (female:male ratio 5:1; Chinese 45.3%, Malay 28.1%, Indian 9.4%, and other races 17.2%) had a mean onset age of 11.5 years (range 2.1-16.7) and mean age at diagnosis was 11.9 years (range 2.6-18.0). Our study demonstrated differences in clinical manifestations for which hematologic involvement was the most common manifestation with less renal disease and uncommon neurologic manifestation as compared to other cSLE cohorts reported in our region. Antibody clusters were identified in our cohort but their clinical association/discrimination and outcome prediction required further validation study. Outcomes of our cohort in regard to disease activity after therapy and organ damages were comparable if not better to other cSLE cohorts elsewhere. Steroid-related damage, including symptomatic multifocal avascular necrosis and cataract, were not uncommon locally. Infection remains the major cause of death for the continent. Nevertheless, the five year survival rate of our cohort (98.4%) was high. © The Author(s) 2015.

  2. Comparing endophenotypes in adult-onset primary torsion dystonia.

    LENUS (Irish Health Repository)

    Bradley, David

    2012-02-01

    Adult-onset primary torsion dystonia (AOPTD) has an autosomal dominant pattern of inheritance with markedly reduced penetrance; the genetic causes of most forms of AOPTD remain unknown. Endophenotypes, markers of sub-clinical gene carriage, may be of use detecting non-manifesting gene carriers in relatives of AOPTD patients. The aim of this study was to compare the utility of the spatial discrimination threshold (SDT) and temporal discrimination threshold (TDT) as potential endophenotypes in AOPTD. Data on other published candidate endophenotypes are also considered. Both SDT and TDT testing were performed in 24 AOPTD patients and 34 of their unaffected first degree relatives; results were compared with normal values from a control population. Of the 24 AOPTD patients 5 (21%) had abnormal SDTs and 20 (83%) had abnormal TDTs. Of the 34 first degree relatives 17 (50%) had abnormal SDTs and 14 (41%) had abnormal TDTs. Discordant results on SDT and TDT testing were found in 16 (67%) AOPTD patients and 21 (62%) first degree relatives. TDT testing has superior sensitivity compared to SDT testing in AOPTD patients; although false positive TDTs are recognised, the specificity of TDT testing in unaffected relatives is not determinable. The high level of discordance between the two tests probably relates methodological difficulties with SDT testing. The SDT is an unreliable AOPTD endophenotype; TDT testing fulfils criteria for a reliable endophenotype with a high sensitivity.

  3. Systematic Search for Primary Immunodeficiency in Adults With Infections

    Science.gov (United States)

    2017-12-21

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

  4. The challenge of growth hormone deficiency (GHD diagnosis and treatment during the transition from puberty into adulthood

    Directory of Open Access Journals (Sweden)

    Stefano eCianfarani

    2013-03-01

    Full Text Available In children with childhood-onset growth hormone deficiency, replacement GH therapy is effective in normalising height during childhood and achieving adult height within the genetic target range. GH has further beneficial effects on body composition and metabolism through adult life. The transition phase, defined as the period from mid to late teens until 6–7 years after the achievement of final height, represents a crucial time for reassessing children’s GH secretion and deciding whether GH therapy should be continued throughout life. Evidence-based guidelines for diagnosis and treatment of GHD children during transition are lacking. The aim of this review is to critically review the up-to-date evidence on the best management of transition patients in order to ensure the correct definitive diagnosis and establish the appropriate therapeutic regimen.

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

    Science.gov (United States)

    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- (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.

  6. Monoclonal Antibody Therapy for Advanced Neuroblastoma

    Science.gov (United States)

    NCI is sponsoring two clinical trials of a monoclonal antibody called ch14.18, in combination with other drugs, to see if the antibody may be helpful for children or young adults (up to age 21) with relapsed or refractory neuroblastoma.

  7. Pernicious anemia and juvenile-onset diabetes mellitus in an adolescent: a case report.

    Science.gov (United States)

    Yu, L C; Warrier, R P; Ducos, R S

    1989-02-01

    We report a case of a 15-year-old black boy who developed juvenile-onset pernicious anemia in association with insulin-dependent diabetes mellitus. He had both intrinsic factor and parietal cell antibodies in addition to anti-islet cell surface antibodies. The existence of pernicious anemia and diabetes mellitus in such a young child makes this an unusual case.

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

    Science.gov (United States)

    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.

  9. Patterns of clinical presentation of adult coeliac disease in a rural setting

    Directory of Open Access Journals (Sweden)

    D'Souza Charles

    2006-09-01

    Full Text Available Abstract Background In recent years there has been increasing recognition that the pattern of presentation of coeliac disease may be changing. The classic sprue syndrome with diarrhoea and weight loss may be less common than the more subtle presentations of coeliac disease such as an isolated iron deficiency anaemia. As a result, the diagnosis of this treatable condition is often delayed or missed. Recent serologic screening tests allow non-invasive screening to identify most patients with the disease and can be applied in patients with even subtle symptoms indicative of coeliac disease. Both benign and malignant complications of coeliac disease can be avoided by early diagnosis and a strict compliance with a gluten free diet. Aim The aim of this study is to evaluate the trends in clinical presentation of patients diagnosed with adult coeliac disease. In addition, we studied the biochemical and serological features and the prevalence of associated conditions in patients with adult coeliac disease. Methods This is an observational, retrospective, cross-sectional review of the medical notes of 32 adult patients attending the specialist coeliac clinic in a district general hospital. Results Anaemia was the most common mode of presentation accounting for 66% of patients. Less than half of the patients had any of the classical symptoms of coeliac disease and 25% had none of the classical symptoms at presentation. Anti-gliadin antibodies, anti-endomysial antibody and anti-tissue transglutaminase showed 75%, 68% and 90% sensitivity respectively. In combination, serology results were 100% sensitive as screening tests for adult coeliac disease. Fifty nine percent patients had either osteoporosis or osteopenia. There were no malignant complications observed during the follow up of our patients. Conclusion Most adults with coeliac disease have a sub clinical form of the disease and iron deficiency anaemia may be its sole presenting symptom. Only a minority

  10. Vitamin D Deficiency

    Science.gov (United States)

    ... to other diseases. In children, it can cause rickets. Rickets is a rare disease that causes the bones ... and children are at higher risk of getting rickets. In adults, severe vitamin D deficiency leads to ...

  11. Measurement of the IgG2 response to Pneumococcal capsular polysaccharides may identify an antibody deficiency in individuals referred for immunological investigation.

    Science.gov (United States)

    Parker, Antony; Irure Ventura, Juan; Sims, Dawn; Echeverría de Carlos, Ainara; Gómez de la Torre, Ricardo; Tricas Aizpún, Lourdes; Ocejo-Vinyals, J Gonzalo; López-Hoyos, Marcos; Wallis, Gregg; Harding, Stephen

    2017-01-01

    IgG2 is the most efficient subclass for providing protection against pneumococcal pathogens. We hypothesised that some individuals may be unable to mount an effective pneumococcal capsular polysaccharide (PCP) IgG2 response despite having a normal PCP IgG concentration (PCP IgG2 deficient). The median pre-vaccination PCP IgG2 concentration was significantly lower in individuals referred for immunological investigation compared to healthy controls (2.8 mg/L range, 95% CI 1.1-88 vs. 29.5mg/L, 95% CI 13.5-90, p = 0.0002). PCP IgG:IgG2 ratios were significantly higher for the referral population than for healthy controls suggesting the increased production of PCP specific subclasses other than IgG2. The percentage of individuals with PCP IgG2 deficiency was significantly higher in referral groups compared to controls (31% vs. 5%; p = 0.0009) and in an individual with PCP IgG2 deficiency, the balance of PCP specific IgG subclass antibodies post vaccination changed from IgG2>IgG1>IgG3>IgG4 to IgG1>IgG3>IgG2>IgG4. The median PCP IgG2 concentration in those with PCP IgG2 deficiency was significantly lower in the referral groups compared to controls (7.8 mg/L, 95% CI 1.1-12 vs. 12.7 mg/L, 95% CI 11.8-13.1; p = 0.006). The data suggests a defect in the production PCP IgG2 may be present in individuals with normal PCP IgG referred for immunological investigation.

  12. Prevalence, determinants and clinical correlates of vitamin D deficiency in adults with inhaled corticosteroid-treated asthma in London, UK.

    Science.gov (United States)

    Jolliffe, David A; Kilpin, Kate; MacLaughlin, Beverley D; Greiller, Claire L; Hooper, Richard L; Barnes, Neil C; Timms, Peter M; Rajakulasingam, Raj K; Bhowmik, Angshu; Choudhury, Aklak B; Simcock, David E; Hyppönen, Elina; Corrigan, Christopher J; Walton, Robert T; Griffiths, Christopher J; Martineau, Adrian R

    2018-01-01

    Vitamin D deficiency is common in children with asthma, and it associates with poor asthma control, reduced forced expiratory volume in one second (FEV 1 ) and increased requirement for inhaled corticosteroids (ICS). Cross-sectional studies investigating the prevalence, determinants and clinical correlates of vitamin D deficiency in adults with asthma are lacking. We conducted a multi-centre cross-sectional study in 297 adults with a medical record diagnosis of ICS-treated asthma living in London, UK. Details of potential environmental determinants of vitamin D status, asthma control and medication use were collected by questionnaire; blood samples were taken for analysis of serum 25(OH)D concentration and DNA extraction, and participants underwent measurement of weight, height and fractional exhaled nitric oxide concentration (FeNO), spirometry and sputum induction for determination of lower airway eosinophil counts (n=35 sub-group). Thirty-five single nucleotide polymorphisms (SNP) in 11 vitamin D pathway genes (DBP, DHCR7, RXRA, CYP2R1, CYP27B1, CYP24A1, CYP3A4 CYP27A1, LRP2, CUBN, VDR) were typed using Taqman allelic discrimination assays. Linear regression was used to identify environmental and genetic factors independently associated with serum 25(OH)D concentration, and to determine whether vitamin D status was independently associated with Asthma Control Test (ACT) score, ICS dose, FeNO, forced vital capacity (FVC), FEV 1 or lower airway eosinophilia. Mean serum 25(OH)D concentration was 50.6nmol/L (SD 24.9); 162/297 (54.5%) participants were vitamin D deficient (serum 25(OH)D concentration asthma control investigated. Vitamin D deficiency is common among UK adults with ICS-treated asthma, and classical environmental determinants of serum 25(OH)D operate in this population. However, in contrast to studies conducted in children, we found no association between vitamin D status and markers of asthma severity or control. Crown Copyright © 2016. Published by

  13. GH-replacement therapy in adults

    DEFF Research Database (Denmark)

    Christiansen, J S; Jørgensen, J O; Pedersen, S A

    1991-01-01

    Growth hormone (GH) deficiency in adults, whether GH deficient since childhood or patients rendered GH deficient in adult life, is associated with psychosocial maladjustment, reduced muscle strength and reduced exercise capacity. Body composition is significantly altered with increased fat and de...

  14. Substance p regulates puberty onset and fertility in the female mouse.

    Science.gov (United States)

    Simavli, Serap; Thompson, Iain R; Maguire, Caroline A; Gill, John C; Carroll, Rona S; Wolfe, Andrew; Kaiser, Ursula B; Navarro, Víctor M

    2015-06-01

    Puberty is a tightly regulated process that leads to reproductive capacity. Kiss1 neurons are crucial in this process by stimulating GnRH, yet how Kiss1 neurons are regulated remains unknown. Substance P (SP), an important neuropeptide in pain perception, induces gonadotropin release in adult mice in a kisspeptin-dependent manner. Here, we assessed whether SP, through binding to its receptor NK1R (neurokinin 1 receptor), participates in the timing of puberty onset and fertility in the mouse. We observed that 1) selective NK1R agonists induce gonadotropin release in prepubertal females; 2) the expression of Tac1 (encoding SP) and Tacr1 (NK1R) in the arcuate nucleus is maximal before puberty, suggesting increased SP tone; 3) repeated exposure to NK1R agonists prepubertally advances puberty onset; and 4) female Tac1(-/-) mice display delayed puberty; moreover, 5) SP deficiency leads to subfertility in females, showing fewer corpora lutea and antral follicles and leading to decreased litter size. Thus, our findings support a role for SP in the stimulation of gonadotropins before puberty, acting via Kiss1 neurons to stimulate GnRH release, and its involvement in the attainment of full reproductive capabilities in female mice.

  15. Antibody blockade of IL-17 family cytokines in immunity to acute murine oral mucosal candidiasis.

    Science.gov (United States)

    Whibley, Natasha; Tritto, Elaine; Traggiai, Elisabetta; Kolbinger, Frank; Moulin, Pierre; Brees, Dominique; Coleman, Bianca M; Mamo, Anna J; Garg, Abhishek V; Jaycox, Jillian R; Siebenlist, Ulrich; Kammüller, Michael; Gaffen, Sarah L

    2016-06-01

    Antibodies targeting IL-17A or its receptor, IL-17RA, are approved to treat psoriasis and are being evaluated for other autoimmune conditions. Conversely, IL-17 signaling is critical for immunity to opportunistic mucosal infections caused by the commensal fungus Candida albicans, as mice and humans lacking the IL-17R experience chronic mucosal candidiasis. IL-17A, IL-17F, and IL-17AF bind the IL-17RA-IL-17RC heterodimeric complex and deliver qualitatively similar signals through the adaptor Act1. Here, we used a mouse model of acute oropharyngeal candidiasis to assess the impact of blocking IL-17 family cytokines compared with specific IL-17 cytokine gene knockout mice. Anti-IL-17A antibodies, which neutralize IL-17A and IL-17AF, caused elevated oral fungal loads, whereas anti-IL-17AF and anti-IL-17F antibodies did not. Notably, there was a cooperative effect of blocking IL-17A, IL-17AF, and IL-17F together. Termination of anti-IL-17A treatment was associated with rapid C. albicans clearance. IL-17F-deficient mice were fully resistant to oropharyngeal candidiasis, consistent with antibody blockade. However, IL-17A-deficient mice had lower fungal burdens than anti-IL-17A-treated mice. Act1-deficient mice were much more susceptible to oropharyngeal candidiasis than anti-IL-17A antibody-treated mice, yet anti-IL-17A and anti-IL-17RA treatment caused equivalent susceptibilities. Based on microarray analyses of the oral mucosa during infection, only a limited number of genes were associated with oropharyngeal candidiasis susceptibility. In sum, we conclude that IL-17A is the main cytokine mediator of immunity in murine oropharyngeal candidiasis, but a cooperative relationship among IL-17A, IL-17AF, and IL-17F exists in vivo. Susceptibility displays the following hierarchy: IL-17RA- or Act1-deficiency > anti-IL-17A + anti-IL-17F antibodies > anti-IL-17A or anti-IL-17RA antibodies > IL-17A deficiency. © Society for Leukocyte Biology.

  16. Gender role across development in adult women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

    Science.gov (United States)

    Long, Dominique N; Wisniewski, Amy B; Migeon, Claude J

    2004-10-01

    This study evaluated the degree of femininity and masculinity at different developmental stages in a group of adult women, some of whom were exposed to elevated prenatal adrenal androgens as a result of congenital adrenal hyperplasia (CAH) due to 21 hydroxylase (21-OH) deficiency. Women who had presented to the Johns Hopkins Hospital Pediatric Endocrine Clinic for treatment of CAH due to 21-OH deficiency were included. The control group consisted of sisters of CAH participants and women referred for evaluation of polycystic ovary syndrome. Study participants were given a questionnaire asking them to indicate their degree of masculinity and femininity during childhood, adolescence, and adulthood. In addition, participants were asked questions related to their play behavior during childhood, including playmate preferences, toy preferences, and admiration of male or female characters during fantasy play. Across participant groups, self-reported femininity decreased in a dose response manner, according to prenatal androgen exposure. For all groups, femininity increased through developmental stages. Women with salt-losing CAH remained less feminine than controls into adulthood. Conversely, self-reported masculinity increased in a dose-response manner, according to prenatal androgen exposure, across participant groups. Women with CAH showed a decrease in masculinity across developmental stages, such that by adulthood, there were no significant differences in masculinity between controls and the women with CAH. Women with salt-losing CAH were more likely to recall preferences for boy playmates, male-typical toys, and admiration for male characters during childhood than other study participants. Our data support the effect of both prenatal androgen exposure and socialization on gender role behavior in adult women with CAH due to 21-OH deficiency.

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia. Learn about the current and future NHLBI efforts to improve health through research and ... blood donors. Cardiovascular Health Study identifies predictors of future health problems in older adults. The NHLBI-sponsored ...

  18. Antibody response to the lipopolysaccharide and protein antigens of Salmonella typhi during typhoid infection. I. Measurement of serum antibodies by radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Tsang, R S.W.; Chau, P Y; Lam, S K [Hong Kong Univ.; La Brooy, J T; Rowley, D [Adelaide Univ. (Australia)

    1981-12-01

    Serum antibody responses to the lipopolysaccharide and protein antigens of S. typhi in typhoid patients were studied using a solid-phase radioimmunoassay technique with /sup 125/I labelled anti-immunoglobulin antibody. Sera from 24 adult typhoid patients and 20 non-typhoid adult controls were compared. As a group, sera from typhoid patients showed increased IgA, IgG and IgM immunoglobulin levels and gave significantly higher anti-LPS and anti-protein antibody titres in all three major immunoglobulin classes than did non-typhoid controls. Levels of antibodies against LPS or protein in sera of typhoid patients were highly variable with a skew distribution. A good correlation was found between antibody titres to the LPS antigen and those to a protein antigen. No correlation, however, was found between the anti-LPS antibody titres measured by radioimmunoassay and the anti-O antibody titres measured by the Widal agglutination test. Titration of anti-LPS or anti-protein antibodies by radioimmunoassay was found to be more sensitive and specific than Widal test for the serological diagnosis of typhoid fever. The advantages of measuring antibody response by radioimmunoassay over conventional Widal test are discussed.

  19. Antibody therapies for lymphoma in children

    NARCIS (Netherlands)

    de Zwart, Verena; Gouw, Samantha C.; Meyer-Wentrup, Friederike A. G.

    2016-01-01

    Lymphomas are the third most common malignancy in childhood. Cure rates are high but have reached a plateau. Therefore new treatment modalities should be developed. Antibody therapy is a successful new treatment option in adult lymphoma. However, none of the therapeutic antibodies available for

  20. Defect in IgV gene somatic hypermutation in common variable immuno-deficiency syndrome.

    Science.gov (United States)

    Levy, Y; Gupta, N; Le Deist, F; Garcia, C; Fischer, A; Weill, J C; Reynaud, C A

    1998-10-27

    Common Variable Immuno-Deficiency (CVID) is the most common symptomatic primary antibody-deficiency syndrome, but the basic immunologic defects underlying this syndrome are not well defined. We report here that among eight patients studied (six CVID and two hypogammaglobulinemic patients with recurrent infections), there is in two CVID patients a dramatic reduction in Ig V gene somatic hypermutation with 40-75% of IgG transcripts totally devoid of mutations in the circulating memory B cell compartment. Functional assays of the T cell compartment point to an intrinsic B cell defect in the process of antibody affinity maturation in these two cases.

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

    Science.gov (United States)

    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.

  2. Rhoh deficiency reduces peripheral T-cell function and attenuates allogenic transplant rejection

    DEFF Research Database (Denmark)

    Porubsky, Stefan; Wang, Shijun; Kiss, Eva

    2011-01-01

    better graft function. This effect was independent of the lower T-cell numbers in Rhoh-deficient recipients, because injection of equal numbers of Rhoh-deficient or control T cells into kidney transplanted mice with SCID led again to a significant 60% reduction of rejection. Mixed lymphocyte reaction...... deficiency in a clinically relevant situation, in which T-cell inhibition is desirable. In murine allogenic kidney transplantation, Rhoh deficiency caused a significant 75% reduction of acute and chronic transplant rejection accompanied by 75% lower alloantigen-specific antibody levels and significantly...

  3. Did hypocretin receptor 2 autoantibodies cause narcolepsy with hypocretin deficiency in Pandemrix-vaccinated children? Comment on “Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2”

    OpenAIRE

    Vassalli Anne

    2015-01-01

    Abstract Did hypocretin receptor 2 auto antibodies cause narcolepsy with hypocretin deficiency in Pandemrix vaccinated children as suggested by Ahmed et al.? Using newly developed mouse models to report and inactivate hypocretin receptor expression Vassalli et al. now show that hypocretin neurons (whose loss causes narcolepsy) do not express hypocretin autoreceptors raising questions to the interpretation of Ahmed et al.’s findings. Mouse Genome Informatics: www.informatics.jax.org/reference/...

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

    Science.gov (United States)

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

    2009-12-01

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

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

    Science.gov (United States)

    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.

  6. Adult onset Leigh syndrome

    Directory of Open Access Journals (Sweden)

    Pandit Lekha

    2007-01-01

    Full Text Available Leigh syndrome is a rare progressive mitochondrial disorder of oxidative metabolism. Though it has been reported in infancy and childhood, it is rarely described in adults. The authors describe a patient who had clinical and magnetic resonance imaging features diagnostic of Leigh syndrome, with supportive biochemical and muscle histochemistry evidence.

  7. High risk of adrenal insufficiency in adults previously treated for idiopathic childhood onset growth hormone deficiency

    DEFF Research Database (Denmark)

    Lange, Martin; Feldt-Rasmussen, Ulla; Svendsen, Ole Lander

    2003-01-01

    were retested with an ITT to evaluate adult GH status. In five patients, an arginine and a synacthen test were performed instead of an ITT. Eleven of 25 patients had a subnormal cortisol response to ITT or synacthen. Ten patients had a GH peak less than 3.0 microg/liter (0.5. +/- 0.5 microg/liter......), whereas 16 patients displayed a normal GH response (12.3 +/- 10.6 microg/liter) after ITT. IGF-I values were decreased in the patients with a pathological retest as well as in patients with a normal GH response compared with controls (P

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

    Science.gov (United States)

    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.

  9. Prevalence of diphtheria and tetanus antibodies among adults in Singapore: a national serological study to identify most susceptible population groups.

    Science.gov (United States)

    Ang, L W; James, L; Goh, K T

    2016-03-01

    In view of waning antitoxin titres over time after the last vaccine dose against diphtheria and tetanus, we determined the immunity levels in adults to identify most susceptible groups for protection in Singapore. Our study involved residual sera from 3293 adults aged 18-79 who had participated in a national health survey in 2010. IgG antibody levels were determined using commercial enzyme-linked immunosorbent assay. Overall, 92.0% (95% confidence interval [CI]: 91.1-92.9%) had at least basic protection against diphtheria (antibody levels ≥0.01 IU/ml), while 71.4% (95% CI: 69.8-72.9%) had at least short-term protection against tetanus (antibody levels >0.1 IU/ml). The seroprevalence declined significantly with age for both diseases; the drop was most marked in the 50- to 59-year age group for diphtheria and 60- to 69-year age group for tetanus. There was a significant difference in seroprevalence by residency for diphtheria (92.8% among Singapore citizens versus 87.1% among permanent residents; P = 0.001). The seroprevalence for tetanus was significantly higher among males (83.2%) than females (62.4%) (P < 0.0005). It may be of value to consider additional vaccination efforts to protect older adults at higher risk for exposure against diphtheria and tetanus, particularly those travelling to areas where diphtheria is endemic or epidemic. © The Author 2015. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Diagnostic impact of routine Lyme serology in recent-onset arthritis: results from the ESPOIR cohort

    Science.gov (United States)

    Guellec, Dewi; Narbonne, Valérie; Cornec, Divi; Marhadour, Thierry; Varache, Sophie; Dougados, Maxime; Daurès, Jean Pierre; Jousse-Joulin, Sandrine; Devauchelle-Pensec, Valérie; Saraux, Alain

    2016-01-01

    Objectives Lyme disease may be considered by rheumatologists in patients with recent-onset arthritis, even in the absence of suggestive symptoms. The aim of this study was to determine the diagnostic impact of routine Lyme serology in a French cohort of patients with recent-onset arthritis affecting at least 2 joints. Methods We performed an ancillary study of a French prospective multicentre cohort established to monitor clinical, biological and radiographic data in patients with inflammatory arthritis in at least 2 joints, lasting for 6 weeks to 6 months. Borrelia IgM and IgG antibodies were sought routinely at baseline, using ELISA tests, independently from the physician's strategy for detecting a spirochetal infection. We recorded the proportion of patients with a final diagnosis of Lyme arthritis and evaluated the diagnostic performance of Lyme serology in this particular context. The clinical and biological characteristics of patients according to the Lyme serology results were analysed. Results Of 810 patients, 657 (81.1%) were negative for IgM and IgG antibodies, 91 (11.2%) had only IgM antibodies, 49 (6%) had only IgG antibodies, and 13 (1.6%) had IgG and IgM antibodies. Thus, 7.6% had IgG positivity, consistent with exposure to Borrelia infection. IgG positivity was significantly more prevalent in the North and North-East regions of France (χ2=14.6, pLyme arthritis. Conclusions This study does not support routine Lyme serological testing in patients with recent-onset inflammatory arthritis affecting more than 1 joint. PMID:26819751

  11. The poor prognosis of childhood-onset bipolar disorder

    NARCIS (Netherlands)

    Leverich, Gabriele S.; Post, Robert M.; Keck, Paul E.; Altshuler, Lori L.; Frye, Mark A.; Kupka, Ralph W.; Nolen, Willem A.; Suppes, Trisha; McElroy, Susan L.; Grunze, Heinz; Denicoff, Kirk; Moravec, Maria K. M.; Luckenbaugh, David

    Objective We examined age of onset of bipolar disorder as a potential course-of-iflness modifier with the hypothesis that early onset will engender more severe illness. Study design A total of 480 carefully diagnosed adult outpatients with bipolar disorder (mean age, 42.5 +/- 11.6 years) were

  12. Three Types of Striational Antibodies in Myasthenia Gravis

    Directory of Open Access Journals (Sweden)

    Shigeaki Suzuki

    2011-01-01

    Full Text Available Myasthenia gravis (MG is caused by antibodies that react mainly with the acetylcholine receptor on the postsynaptic site of the neuromuscular junction. A wide range of clinical presentations and associated features allow MG to be classified into subtypes based on autoantibody status. Striational antibodies, which react with epitopes on the muscle proteins titin, ryanodine receptor (RyR, and Kv1.4, are frequently found in MG patients with late-onset and thymoma. Antititin and anti-RyR antibodies are determined by enzyme-linked immunosorbent assay or immunoblot. More recently, a method for the detection of anti-Kv1.4 autoantibodies has become available, involving 12–15% of all MG patients. The presence of striational antibodies is associated with more severe disease in all MG subgroups. Anti-Kv1.4 antibody is a useful marker for the potential development of lethal autoimmune myocarditis and response to calcineurin inhibitors. Detection of striational antibodies provides more specific and useful clinical information in MG patients.

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

    Science.gov (United States)

    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.

  14. Epidemiology of myasthenia gravis with anti-muscle specific kinase antibodies in the Netherlands

    NARCIS (Netherlands)

    Niks, Erik H.; Kuks, Jan B. M.; Verschuuren, Jan J. G. M.

    The epidemiology of myasthenia gravis subtypes and the frequency of antibodies to muscle-specific kinase (MuSK) was studied in patients with generalised myasthenia gravis without anti-acetylcholine receptor antibodies who had an onset of symptoms between 1990 and 2004 in a well-defined region in the

  15. Genetics Home Reference: alpha-methylacyl-CoA racemase deficiency

    Science.gov (United States)

    ... racemase deficiency Sources for This Page Dick D, Horvath R, Chinnery PF. AMACR mutations cause late-onset ... Citation on PubMed Ferdinandusse S, Denis S, IJlst L, Dacremont G, Waterham HR, Wanders RJ. Subcellular localization and physiological ...

  16. Quantitative proteomics suggests metabolic reprogramming during ETHE1 deficiency

    DEFF Research Database (Denmark)

    Sahebekhtiari, Navid; Thomsen, Michelle M.; Sloth, Jens Jørgen

    2016-01-01

    Deficiency of mitochondrial sulfur dioxygenase (ETHE1) causes the severe metabolic disorder ethylmalonic encephalopathy, which is characterized by early-onset encephalopathy and defective cytochrome C oxidase because of hydrogen sulfide accumulation. Although the severe systemic consequences of t...

  17. Cognitive impairments and mood disturbances in growth hormone deficient men

    NARCIS (Netherlands)

    Deijen, J.B.; de Boer, H.; Blok, G.J.; van der Veen, E.A.

    1996-01-01

    In order to establish whether reported psychological complaints in hypopituitary adults are related to growth hormone (GH) deficiency or other pituitary hormone deficiencies, emotional well-being and cognitive performance were evaluated in 31 men with multiple pituitary hormone deficiencies (MPHD)

  18. Age of onset and the subclassification of conduct/dissocial disorder.

    Science.gov (United States)

    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

  19. Typical versus delayed speech onset influences verbal reporting of autistic interests.

    Science.gov (United States)

    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

  20. Hyperammonemia due to Adult-Onset N-Acetylglutamate Synthase Deficiency

    NARCIS (Netherlands)

    Logt, A.E. van de; Kluijtmans, L.A.J.; Huigen, M.C.; Janssen, M.C.H.

    2017-01-01

    A 59-year-old woman, with a medical history of intellectual disability after perinatal asphyxia, was admitted because of coma due to hyperammonemia after she was treated for a fracture of the pelvis. The ammonia level was 280 muM. Acquired disorders as explanation for the hyperammonemia were

  1. Early-onset childhood sarcoidosis: a case report

    Directory of Open Access Journals (Sweden)

    Lai-San Wong

    2011-12-01

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

  2. IL-25 inhibits atherosclerosis development in apolipoprotein E deficient mice.

    Directory of Open Access Journals (Sweden)

    Polyxeni T Mantani

    Full Text Available IL-25 has been implicated in the initiation of type 2 immunity and in the protection against autoimmune inflammatory diseases. Recent studies have identified the novel innate lymphoid type 2 cells (ILC2s as an IL-25 target cell population. The purpose of this study was to evaluate if IL-25 has any influence on atherosclerosis development in mice.Administration of 1 μg IL-25 per day for one week to atherosclerosis-prone apolipoprotein (apoE deficient mice, had limited effect on the frequency of T cell populations, but resulted in a large expansion of ILC2s in the spleen. The expansion was accompanied by increased levels of anti-phosphorylcholine (PC natural IgM antibodies in plasma and elevated levels of IL-5 in plasma and spleen. Transfer of ILC2s to apoE deficient mice elevated the natural antibody-producing B1a cell population in the spleen. Treatment of apoE/Rag-1 deficient mice with IL-25 was also associated with extensive expansion of splenic ILC2s and increased plasma IL-5, suggesting ILC2s to be the source of IL-5. Administration of IL-25 in IL-5 deficient mice resulted in an expanded ILC2 population, but did not stimulate generation of anti-PC IgM, indicating that IL-5 is not required for ILC2 expansion but for the downstream production of natural antibodies. Additionally, administration of 1 μg IL-25 per day for 4 weeks in apoE deficient mice reduced atherosclerosis in the aorta both during initiation and progression of the disease.The present findings demonstrate that IL-25 has a protective role in atherosclerosis mediated by innate responses, including ILC2 expansion, increased IL-5 secretion, B1a expansion and natural anti-PC IgM generation, rather than adaptive Th2 responses.

  3. Serum thyroglobulin as a biomarker of iodine deficiency in adult populations

    DEFF Research Database (Denmark)

    Krejbjerg, Anne; Bjergved, Lena; Bülow Pedersen, Inge

    2016-01-01

    OBJECTIVE: To clarify which factors may influence the serum Tg level in an adult population and how this may affect Tg as a biomarker of iodine deficiency (ID). DESIGN AND METHODS: Two identical cross-sectional studies were performed before (C1a: 1997-98, n = 4649) and after (C2: 2004-05, n = 3570......) the Danish mandatory iodine fortification (IF) of salt (2000). Additionally, a follow-up study of C1a was performed after IF (C1b: 2008-10, n = 2465). The studies took place in two regions with mild (Copenhagen) and moderate (Aalborg) ID before IF. Serum Tg was measured by immunoradiometric method...... and investigated as outcome variable in multivariate models. RESULTS: Multiple factors were associated with serum Tg. Some were directly related to iodine intake (cohort, urinary iodine concentration (UIC) level and region), and some were likely mediators of iodine intake effects on Tg (thyroid nodularity, thyroid...

  4. Refractory status epilepticus and glutamic acid decarboxylase antibodies in adults: presentation, treatment and outcomes.

    Science.gov (United States)

    Khawaja, Ayaz M; Vines, Brannon L; Miller, David W; Szaflarski, Jerzy P; Amara, Amy W

    2016-03-01

    Glutamic acid decarboxylase antibodies (GAD-Abs) have been implicated in refractory epilepsy. The association with refractory status epilepticus in adults has been rarely described. We discuss our experience in managing three adult patients who presented with refractory status epilepticus associated with GAD-Abs. Case series with retrospective chart and literature review. Three patients without pre-existing epilepsy who presented to our institution with generalized seizures between 2013 and 2014 were identified. Seizures proved refractory to first and second-line therapies and persisted beyond 24 hours. Patient 1 was a 22-year-old female who had elevated serum GAD-Ab titres at 0.49 mmol/l (normal: status epilepticus. Causation cannot be established since GAD-Abs may be elevated secondary to concurrent autoimmune diseases or formed de novo in response to GAD antigen exposure by neuronal injury. Based on this report and available literature, there may be a role for immuno- and chemotherapy in the management of refractory status epilepticus associated with GAD-Abs.

  5. Clinical and Molecular Heterogeneity of RTEL1 Deficiency

    Directory of Open Access Journals (Sweden)

    Marcin W. Wlodarski

    2017-05-01

    . Whether chemotherapy negatively impacts on the course and onset of other DC-related symptoms remains open at present. Early-onset lung disease occurred in one of our patients after HSCT. In conclusion, RTEL deficiency can show a heterogeneous clinical picture ranging from mild hypocellular BMF with B/NK cell lymphopenia to early-onset, very severe, and rapidly progressing cellular deficiency.

  6. Clinical and Molecular Heterogeneity of RTEL1 Deficiency.

    Science.gov (United States)

    Speckmann, Carsten; Sahoo, Sushree Sangita; Rizzi, Marta; Hirabayashi, Shinsuke; Karow, Axel; Serwas, Nina Kathrin; Hoemberg, Marc; Damatova, Natalja; Schindler, Detlev; Vannier, Jean-Baptiste; Boulton, Simon J; Pannicke, Ulrich; Göhring, Gudrun; Thomay, Kathrin; Verdu-Amoros, J J; Hauch, Holger; Woessmann, Wilhelm; Escherich, Gabriele; Laack, Eckart; Rindle, Liliana; Seidl, Maximilian; Rensing-Ehl, Anne; Lausch, Ekkehart; Jandrasits, Christine; Strahm, Brigitte; Schwarz, Klaus; Ehl, Stephan R; Niemeyer, Charlotte; Boztug, Kaan; Wlodarski, Marcin W

    2017-01-01

    chemotherapy negatively impacts on the course and onset of other DC-related symptoms remains open at present. Early-onset lung disease occurred in one of our patients after HSCT. In conclusion,