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Sample records for disease undergo disease-like

  1. Genetics Home Reference: Huntington disease-like syndrome

    MedlinePlus

    ... are responsible for HDL4 (also known as spinocerebellar ataxia type 17). The genetic cause of HDL3 is ... syndrome: GeneReview: Huntington Disease-Like 2 GeneReview: Spinocerebellar Ataxia Type 17 Genetic Testing Registry: Huntington disease-like ...

  2. Chronic unremitting headache associated with Lyme disease-like illness.

    PubMed

    Kowacs, Pedro André; Martins, Rodrigo Tomazini; Piovesan, Elcio Juliato; Pinto, Maria Cristina Araujo; Yoshinari, Natalino Hagime

    2013-07-01

    The Brazilian Lyme-disease-like illness (BLDLI) or Baggio-Yoshinari syndrome is a unique zoonosis found in Brazil. It reproduces all the clinical symptoms of Lyme disease except for the high frequencies of relapse and the presence of autoimmune manifestations. Two cases of borreliosis manifesting with unremitting headache, which is a symptom associated with late-stage BLDLI, were presented. Clinical, therapeutic, and prognostic aspects of the BLDLI and its associated headaches were showed and discussed in this article. BLDLI diagnosis requires additional attention by physicians, since the disease has a tendency to progress to the late, recurrent stage or the chronic form, and the associated headache can be confused with chronic primary headache or with analgesic-overuse one. Special attention should be paid to patients with headaches who have traveled to endemic areas. PMID:23857618

  3. The neuropsychiatric manifestations of Huntington's disease-like 2.

    PubMed

    Fischer, Christopher A; Licht, Eliot A; Mendez, Mario F

    2012-01-01

    Huntington's disease-like 2 (HDL2) is a rare neuropsychiatric disorder that resembles HD but results from a distinct mutation. The authors present a patient with HDL2, hospitalized for psychiatric management, and they review the neuropsychiatric manifestations of this disorder. Depression, irritability/aggression, and frontal lobe personality changes are common presentations of HDL2 and are comparable to classic HD. Patients with HDL2 may differ from those with HD in having a lower incidence of obsessive-compulsive acts, known suicides, antisocial acts, and changes in sexuality. Clinicians should be aware of the psychiatric presentations of this disorder, when to obtain genetic testing, and how to manage problematic behaviors. PMID:23224457

  4. Neutrophils promote Alzheimer's disease-like pathology and cognitive decline via LFA-1 integrin.

    PubMed

    Zenaro, Elena; Pietronigro, Enrica; Della Bianca, Vittorina; Piacentino, Gennj; Marongiu, Laura; Budui, Simona; Turano, Ermanna; Rossi, Barbara; Angiari, Stefano; Dusi, Silvia; Montresor, Alessio; Carlucci, Tommaso; Nanì, Sara; Tosadori, Gabriele; Calciano, Lucia; Catalucci, Daniele; Berton, Giorgio; Bonetti, Bruno; Constantin, Gabriela

    2015-08-01

    Inflammation is a pathological hallmark of Alzheimer's disease, and innate immune cells have been shown to contribute to disease pathogenesis. In two transgenic models of Alzheimer's disease (5xFAD and 3xTg-AD mice), neutrophils extravasated and were present in areas with amyloid-β (Aβ) deposits, where they released neutrophil extracellular traps (NETs) and IL-17. Aβ42 peptide triggered the LFA-1 integrin high-affinity state and rapid neutrophil adhesion to integrin ligands. In vivo, LFA-1 integrin controlled neutrophil extravasation into the CNS and intraparenchymal motility. In transgenic Alzheimer's disease models, neutrophil depletion or inhibition of neutrophil trafficking via LFA-1 blockade reduced Alzheimer's disease-like neuropathology and improved memory in mice already showing cognitive dysfunction. Temporary depletion of neutrophils for 1 month at early stages of disease led to sustained improvements in memory. Transgenic Alzheimer's disease model mice lacking LFA-1 were protected from cognitive decline and had reduced gliosis. In humans with Alzheimer's disease, neutrophils adhered to and spread inside brain venules and were present in the parenchyma, along with NETs. Our results demonstrate that neutrophils contribute to Alzheimer's disease pathogenesis and cognitive impairment and suggest that the inhibition of neutrophil trafficking may be beneficial in Alzheimer's disease. PMID:26214837

  5. Pyrosequencing revealed shifts of prokaryotic communities between healthy and disease-like tissues of the Red Sea sponge Crella cyathophora

    PubMed Central

    Gao, Zhao-Ming; Wang, Yong; Tian, Ren-Mao; Lee, On On; Wong, Yue Him; Batang, Zenon B.; Al-Suwailem, Abdulaziz; Lafi, Feras F.; Bajic, Vladimir B.

    2015-01-01

    Sponge diseases have been widely reported, yet the causal factors and major pathogenic microbes remain elusive. In this study, two individuals of the sponge Crella cyathophora in total that showed similar disease-like characteristics were collected from two different locations along the Red Sea coast separated by more than 30 kilometers. The disease-like parts of the two individuals were both covered by green surfaces, and the body size was much smaller compared with adjacent healthy regions. Here, using high-throughput pyrosequencing technology, we investigated the prokaryotic communities in healthy and disease-like sponge tissues as well as adjacent seawater. Microbes in healthy tissues belonged mainly to the Proteobacteria, Cyanobacteria and Bacteroidetes, and were much more diverse at the phylum level than reported previously. Interestingly, the disease-like tissues from the two sponge individuals underwent shifts of prokaryotic communities and were both enriched with a novel clade affiliated with the phylum Verrucomicrobia, implying its intimate connection with the disease-like Red Sea sponge C. cyathophora. Enrichment of the phylum Verrucomicrobia was also considered to be correlated with the presence of algae assemblages forming the green surface of the disease-like sponge tissues. This finding represents an interesting case of sponge disease and is valuable for further study. PMID:26082867

  6. Memantine Attenuates Alzheimer’s Disease-Like Pathology and Cognitive Impairment

    PubMed Central

    Wang, Xiaochuan; Blanchard, Julie; Iqbal, Khalid

    2015-01-01

    Deficiency of protein phosphatase-2A is a key event in Alzheimer’s disease. An endogenous inhibitor of protein phosphatase-2A, inhibitor-1, I1PP2A, which inhibits the phosphatase activity by interacting with its catalytic subunit protein phosphatase-2Ac, is known to be upregulated in Alzheimer’s disease brain. In the present study, we overexpressed I1PP2A by intracerebroventricular injection with adeno-associated virus vector-1-I1PP2A in Wistar rats. The I1PP2A rats showed a decrease in brain protein phosphatase-2A activity, abnormal hyperphosphorylation of tau, neurodegeneration, an increase in the level of activated glycogen synthase kinase-3beta, enhanced expression of intraneuronal amyloid-beta and spatial reference memory deficit; littermates treated identically but with vector only, i.e., adeno-associated virus vector-1-enhanced GFP, served as a control. Treatment with memantine, a noncompetitive NMDA receptor antagonist which is an approved drug for treatment of Alzheimer’s disease, rescued protein phosphatase-2A activity by decreasing its demethylation at Leu309 selectively and attenuated Alzheimer’s disease-like pathology and cognitive impairment in adeno-associated virus vector-1-I1PP2A rats. These findings provide new clues into the possible mechanism of the beneficial therapeutic effect of memantine in Alzheimer’s disease patients. PMID:26697860

  7. Acute Monocytic Leukemia Masquerading Behçet's Disease-Like Illness at Onset in an Elderly Female.

    PubMed

    Koba, Shigeru; Sekioka, Toshio; Takeda, Sorou; Miyagawa-Hayashino, Aya; Nishimura, Keisuke; Imashuku, Shinsaku

    2016-01-01

    A previously healthy 74-year-old Japanese female was hospitalized with fever and high C-reactive protein. She developed palatal herpangina-like aphthous ulcers, localized intestinal wall thickening, terminal ileum ulcers, and an erythematous acneiform rash; thus Behçet's disease-like illness was suspected. Significant peripheral blood acute monocytosis developed during her hospitalization and acute monocytic leukemia (FAB M5b) with normal karyotype was diagnosed. By immunostaining, the infiltrating cells in the skin and the terminal ileum were identified as monocytic leukemic cells. This case exhibited a unique initial presentation of Behçet's disease-like illness associated with acute monocytic leukemia. PMID:27610252

  8. Acute Monocytic Leukemia Masquerading Behçet's Disease-Like Illness at Onset in an Elderly Female

    PubMed Central

    Koba, Shigeru; Sekioka, Toshio; Takeda, Sorou; Miyagawa-Hayashino, Aya; Nishimura, Keisuke

    2016-01-01

    A previously healthy 74-year-old Japanese female was hospitalized with fever and high C-reactive protein. She developed palatal herpangina-like aphthous ulcers, localized intestinal wall thickening, terminal ileum ulcers, and an erythematous acneiform rash; thus Behçet's disease-like illness was suspected. Significant peripheral blood acute monocytosis developed during her hospitalization and acute monocytic leukemia (FAB M5b) with normal karyotype was diagnosed. By immunostaining, the infiltrating cells in the skin and the terminal ileum were identified as monocytic leukemic cells. This case exhibited a unique initial presentation of Behçet's disease-like illness associated with acute monocytic leukemia. PMID:27610252

  9. Myelin-associated glycoprotein gene mutation causes Pelizaeus-Merzbacher disease-like disorder.

    PubMed

    Lossos, Alexander; Elazar, Nimrod; Lerer, Israela; Schueler-Furman, Ora; Fellig, Yakov; Glick, Benjamin; Zimmerman, Bat-El; Azulay, Haim; Dotan, Shlomo; Goldberg, Sharon; Gomori, John M; Ponger, Penina; Newman, J P; Marreed, Hodaifah; Steck, Andreas J; Schaeren-Wiemers, Nicole; Mor, Nofar; Harel, Michal; Geiger, Tamar; Eshed-Eisenbach, Yael; Meiner, Vardiella; Peles, Elior

    2015-09-01

    Pelizaeus-Merzbacher disease is an X-linked hypomyelinating leukodystrophy caused by mutations or rearrangements in PLP1. It presents in infancy with nystagmus, jerky head movements, hypotonia and developmental delay evolving into spastic tetraplegia with optic atrophy and variable movement disorders. A clinically similar phenotype caused by recessive mutations in GJC2 is known as Pelizaeus-Merzbacher-like disease. Both genes encode proteins associated with myelin. We describe three siblings of a consanguineous family manifesting the typical infantile-onset Pelizaeus-Merzbacher disease-like phenotype slowly evolving into a form of complicated hereditary spastic paraplegia with mental retardation, dysarthria, optic atrophy and peripheral neuropathy in adulthood. Magnetic resonance imaging and spectroscopy were consistent with a demyelinating leukodystrophy. Using genetic linkage and exome sequencing, we identified a homozygous missense c.399C>G; p.S133R mutation in MAG. This gene, previously associated with hereditary spastic paraplegia, encodes myelin-associated glycoprotein, which is involved in myelin maintenance and glia-axon interaction. This mutation is predicted to destabilize the protein and affect its tertiary structure. Examination of the sural nerve biopsy sample obtained in childhood in the oldest sibling revealed complete absence of myelin-associated glycoprotein accompanied by ill-formed onion-bulb structures and a relatively thin myelin sheath of the affected axons. Immunofluorescence, cell surface labelling, biochemical analysis and mass spectrometry-based proteomics studies in a variety of cell types demonstrated a devastating effect of the mutation on post-translational processing, steady state expression and subcellular localization of myelin-associated glycoprotein. In contrast to the wild-type protein, the p.S133R mutant was retained in the endoplasmic reticulum and was subjected to endoplasmic reticulum-associated protein degradation by the

  10. Isolation Housing Exacerbates Alzheimer’s Disease-Like Pathophysiology in Aged APP/PS1 Mice

    PubMed Central

    Huang, Huang; Wang, Linmei; Cao, Min; Marshall, Charles; Gao, Junying; Xiao, Na; Hu, Gang

    2015-01-01

    Background: Alzheimer’s disease is a neurodegenerative disease characterized by gradual declines in social, cognitive, and emotional functions, leading to a loss of expected social behavior. Social isolation has been shown to have adverse effects on individual development and growth as well as health and aging. Previous experiments have shown that social isolation causes an early onset of Alzheimer’s disease-like phenotypes in young APP695/PS1-dE9 transgenic mice. However, the interactions between social isolation and Alzheimer’s disease still remain unknown. Methods: Seventeen-month-old male APP695/PS1-dE9 transgenic mice were either singly housed or continued group housing for 3 months. Then, Alzheimer’s disease-like pathophysiological changes were evaluated by using behavioral, biochemical, and pathological analyses. Results: Isolation housing further promoted cognitive dysfunction and Aβ plaque accumulation in the hippocampus of aged APP695/PS1-dE9 transgenic mice, associated with increased γ-secretase and decreased neprilysin expression. Furthermore, exacerbated hippocampal atrophy, synapse and myelin associated protein loss, and glial neuroinflammatory reactions were observed in the hippocampus of isolated aged APP695/PS1-dE9 transgenic mice. Conclusions: The results demonstrate that social isolation exacerbates Alzheimer’s disease-like pathophysiology in aged APP695/PS1-dE9 transgenic mice, highlighting the potential role of group life for delaying or counteracting the Alzheimer’s disease process. PMID:25568286

  11. Familial Prion Disease with Alzheimer Disease-Like Tau Pathology and Clinical Phenotype

    PubMed Central

    Jayadev, Suman; Nochlin, David; Poorkaj, Parvoneh; Steinbart, Ellen J.; Mastrianni, James A.; Montine, Thomas J.; Ghetti, Bernardino; Schellenberg, Gerard D.; Bird, Thomas D.; Leverenz, James B.

    2011-01-01

    Objective To describe the Alzheimer disease (AD)-like clinical and pathological features, including marked neurofibrillary tangle (NFT) pathology, of a familial prion disease due to a rare nonsense mutation of the prion gene (PRNP). Methods Longitudinal clinical assessments were available for the proband and her mother. After death, both underwent neuropathological evaluation. PRNP was sequenced after failure to find immunopositive Aβ deposits in the proband and the documentation of prion protein (PrP) immunopositive pathology. Results The proband presented at age 42 years with a 3-year history of progressive short-term memory impairment and depression. Neuropsychological testing found impaired memory performance, with relatively preserved attention and construction. She was diagnosed with AD and died at age 47 years. Neuropathologic evaluation revealed extensive limbic and neocortical NFT formation and neuritic plaques consistent with a Braak stage of VI. The NFTs were immunopositive, with multiple tau antibodies, and electron microscopy revealed paired helical filaments. However, the neuritic plaques were immunonegative for Aβ, whereas immunostaining for PrP was positive. The mother of the proband had a similar presentation, including depression, and had been diagnosed clinically and pathologically as AD. Reevaluation of her brain tissue confirmed similar tau and PrP immunostaining findings. Genetic analysis revealed that both the proband and her mother had a rare PRNP mutation (Q160X) that resulted in the production of truncated PrP. Interpretation We suggest that PRNP mutations that result in a truncation of PrP lead to a prolonged clinical course consistent with a clinical diagnosis of AD and severe AD-like NFTs. PMID:21416485

  12. Psittacine beak and feather disease-like illness in Gouldian finches (Chloebia gouldiae).

    PubMed

    Circella, Elena; Legretto, Marilisa; Pugliese, Nicola; Caroli, Anna; Bozzo, Giancarlo; Accogli, Gianluca; Lavazza, Antonio; Camarda, Antonio

    2014-09-01

    Beak and feather disease virus (BFDV) is a member of the genus Circovirus and causes psittacine beak and feather disease (PBFD) in Psittaciformes. PBFD is a severe disease generally characterized by immunodeficiency and beak and feather disorders. Although Circovirus spp. have been detected in several nonpsittacine species, little is known about the symptoms and the disease associated with this infection in birds other than Psittaciformes. In this study, we report the identification of Circovirus infection in a flock of Gouldian finches showing beak and feather disorders. Sequence analyses on the rep gene of the virus highlighted a strong similarity at nucleotide and amino acid levels with the corresponding regions of BFDV from psittacine species. By contrast, it was more distant to circoviruses identified in finch and canary. PMID:25518446

  13. A transmissible Creutzfeldt-Jakob disease-like agent is prevalent in the human population.

    PubMed Central

    Manuelidis, E E; Manuelidis, L

    1993-01-01

    The etiology of most human dementias is unknown. Creutzfeldt-Jakob disease (CJD), a relatively uncommon human dementia, is caused by a transmissible virus-like agent. Molecular markers that are specific for the agent have not yet been defined. However, the infectious disease can be transmitted to rodents from both brain and infected buffy coat (blood) samples. To determine whether human CJD infections are more widespread than is apparent from the low incidence of neurological disease, we attempted to transmit CJD from buffy coat samples of 30 healthy volunteers who had no family history of dementing illness. Primary transmissions from 26 of 30 individuals produced CJD-like spongiform changes in the brains of recipient hamsters at 200-500 days postinoculation. This positive evidence of viremia was found for individuals in all age groups (20-30, 40-50, and 61-71 years old), whereas 12 negatively scored brain samples failed to produce similar changes in hamsters observed for > 900 days in the same setting. We suggest that a CJD agent endemically infects humans but only infrequently produces an infectious dementia. Disease expression is likely to be influenced by several host factors in combination with viral variants that have altered neurovirulence. Images Fig. 1 PMID:8356076

  14. Dysbiotic gut microbiota causes transmissible Crohn's disease-like ileitis independent of failure in antimicrobial defence

    PubMed Central

    Clavel, Thomas; Calasan, Jelena; Lagkouvardos, Ilias; Haange, Sven Bastiaan; Jehmlich, Nico; Basic, Marijana; Dupont, Aline; Hornef, Mathias; von Bergen, Martin; Bleich, André; Haller, Dirk

    2016-01-01

    Objectives Dysbiosis of the intestinal microbiota is associated with Crohn's disease (CD). Functional evidence for a causal role of bacteria in the development of chronic small intestinal inflammation is lacking. Similar to human pathology, TNFdeltaARE mice develop a tumour necrosis factor (TNF)-driven CD-like transmural inflammation with predominant ileal involvement. Design Heterozygous TNFdeltaARE mice and wildtype (WT) littermates were housed under conventional (CONV), specific pathogen-free (SPF) and germ-free (GF) conditions. Microbial communities were analysed by high-throughput 16S ribosomal RNA gene sequencing. Metaproteomes were measured using LC-MS. Temporal and spatial resolution of disease development was followed after antibiotic treatment and transfer of microbial communities into GF mice. Granulocyte infiltration and Paneth cell function was assessed by immunofluorescence and gene expression analysis. Results GF-TNFdeltaARE mice were free of inflammation in the gut and antibiotic treatment of CONV-TNFdeltaARE mice attenuated ileitis but not colitis, demonstrating that disease severity and location are microbiota-dependent. SPF-TNFdeltaARE mice developed distinct ileitis-phenotypes associated with gradual loss of antimicrobial defence. 16S analysis and metaproteomics revealed specific compositional and functional alterations of bacterial communities in inflamed mice. Transplantation of disease-associated but not healthy microbiota transmitted CD-like ileitis to GF-TNFdeltaARE recipients and triggered loss of lysozyme and cryptdin-2 expression. Monoassociation of GF-TNFdeltaARE mice with the human CD-related Escherichia coli LF82 did not induce ileitis. Conclusions We provide clear experimental evidence for the causal role of gut bacterial dysbiosis in the development of chronic ileal inflammation with subsequent failure of Paneth cell function. PMID:25887379

  15. Biodistribution of Infused Human Umbilical Cord Blood Cells in Alzheimer's Disease-Like Murine Model.

    PubMed

    Ehrhart, Jared; Darlington, Donna; Kuzmin-Nichols, Nicole; Sanberg, Cyndy D; Sawmiller, Darrell R; Sanberg, Paul R; Tan, Jun

    2016-01-01

    Human umbilical cord blood cells (HUCBCs), a prolific source of non-embryonic or adult stem cells, have emerged as effective and relatively safe immunomodulators and neuroprotectors, reducing behavioral impairment in animal models of Alzheimer's disease (AD), Parkinson's disease, amyotrophic lateral sclerosis, traumatic brain injury, spinal cord injury, and stroke. In this report, we followed the bioavailability of HUCBCs in AD-like transgenic PSAPP mice and nontransgenic Sprague-Dawley rats. HUCBCs were injected into tail veins of mice or rats at a single dose of 1 × 10(6) or 2.2 × 10(6) cells, respectively, prior to harvesting of tissues at 24 h, 7 days, and 30 days after injection. For determination of HUCBC distribution, tissues from both species were subjected to total DNA isolation and polymerase chain reaction (PCR) amplification of the gene for human glycerol-3-phosphate dehydrogenase. Our results show a relatively similar biodistribution and retention of HUCBCs in both mouse and rat organs. HUCBCs were broadly detected both in the brain and several peripheral organs, including the liver, kidney, and bone marrow, of both species, starting within 7 days and continuing up to 30 days posttransplantation. No HUCBCs were recovered in the peripheral circulation, even at 24 h posttransplantation. Therefore, HUCBCs reach several tissues including the brain following a single intravenous treatment, suggesting that this route can be a viable method of administration of these cells for the treatment of neurodegenerative diseases. PMID:26414627

  16. Ethical problems faced in villages of rural Bengal while conducting researches on chronic diseases like diabetes.

    PubMed

    Mitra, Analava; Bhattacharya, D

    2006-11-01

    India is facing an explosion of diabetes and related diseases. Health infrastructure in rural India is very poor. A large number of rural Indians are below poverty line. To overcome the problem of insulin resistance in rural India, the authors conducted studies with nutraceuticals and came across many sociocultural, socio-political and socioeconomic constraints to faithfully following ethical guidelines of Indian Council of Medical Research (ICMR). This paper deals with some of the constraints and it is strongly felt that the ICMR should review its guidelines in the context of the existing situation. PMID:17090871

  17. Alzheimer's disease-like impaired cognition in endothelial-specific megalin-null mice.

    PubMed

    Dietrich, Marcelo; Antequera, Desiree; Pascual, Consuelo; Castro, Nerea; Bolos, Marta; Carro, Eva

    2014-01-01

    Megalin has been suggested to be involved in Alzheimer's disease (AD), mediating blood-brain barrier (BBB) transport of multiple ligands, including amyloid-β peptide (Aβ), but also neuroprotective factors. Because no transgenic model is currently available to study this concept, we have obtained transgenic mice blocking megalin expression at the BBB. These endothelial megalin deficient (EMD) mice developed increased anxiety behavior and impaired learning ability and recognition memory, similar to symptoms described in AD. Degenerating neurons were also observed in the cerebral cortex of EMD mice. In view of our findings we suggest that, in mice, megalin deficiency at the BBB leads to neurodegeneration. PMID:24254699

  18. Alzheimer's disease-like pathology has transient effects on the brain and blood metabolome.

    PubMed

    Pan, Xiaobei; Nasaruddin, Muhammad Bin; Elliott, Christopher T; McGuinness, Bernadette; Passmore, Anthony P; Kehoe, Patrick G; Hölscher, Christian; McClean, Paula L; Graham, Stewart F; Green, Brian D

    2016-02-01

    The pathogenesis of Alzheimer's disease (AD) is complex involving multiple contributing factors. The extent to which AD pathology affects the metabolome is still not understood nor is it known how disturbances change as the disease progresses. For the first time, we have profiled longitudinally (6, 8, 10, 12, and 18 months) both the brain and plasma metabolome of APPswe/PS1deltaE9 double transgenic and wild-type mice. A total of 187 metabolites were quantified using a targeted metabolomic methodology. Multivariate statistical analysis produced models that distinguished APPswe/PS1deltaE9 from wild-type mice at 8, 10, and 12 months. Metabolic pathway analysis found perturbed polyamine metabolism in both brain and blood plasma. There were other disturbances in essential amino acids, branched-chain amino acids, and also in the neurotransmitter serotonin. Pronounced imbalances in phospholipid and acylcarnitine homeostasis were evident in 2 age groups. AD-like pathology, therefore, affects greatly on both the brain and blood metabolomes, although there appears to be a clear temporal sequence whereby changes to brain metabolites precede those in blood. PMID:26827653

  19. The etiology of Ebola virus disease-like illnesses in Ebola virusnegative patients from Sierra Leone.

    PubMed

    Li, Wen-Gang; Chen, Wei-Wei; Li, Lei; Ji, Dong; Ji, Ying-Jie; Li, Chen; Gao, Xu-Dong; Wang, Li-Fu; Zhao, Min; Duan, Xue-Zhang; Duan, Hui-Juan

    2016-05-10

    During the 2014 Ebola virus disease (EVD) outbreak, less than half of EVD-suspected cases were laboratory tested as Ebola virus (EBOV)-negative, but disease identity remained unknown. In this study we investigated the etiology of EVD-like illnesses in EBOV-negative cases. From November 13, 2014 to March 16, 2015, EVD-suspected patients were admitted to Jui Government Hospital and assessed for EBOV infection by real-time PCR. Of 278 EBOV negative patients, 223 (80.21%), 142 (51.08%), 123 (44.24%), 114 (41.01%), 59 (21.22%), 35 (12.59%), and 12 (4.32%) reported fever, headache, joint pain, fatigue, nausea/vomiting, diarrhea, hemorrhage, respectively. Furthermore, 121 (43.52%), 44 (15.83%), 36 (12.95%), 33 (11.87%), 23 (8.27%), 10 (3.60%) patients were diagnosed as infection with malaria, HIV, Lassa fever, tuberculosis, yellow fever, and pneumonia, respectively. No significant differences in clinical features and symptoms were found between non-EVD and EVD patients. To the best of our knowledge, the present study is the first to explore the etiology of EVD-like illnesses in uninfected patients in Sierra Leone, highlighting the importance of accurate diagnosis to EVD confirmation. PMID:27058894

  20. Histopathological Characteristics of Post-inflamed Coronary Arteries in Kawasaki Disease-like Vasculitis of Rabbits.

    PubMed

    Fujii, Maiko; Tanaka, Hideo; Nakamura, Akihiro; Suzuki, Chinatsu; Harada, Yoshinori; Takamatsu, Tetsuro; Hamaoka, Kenji

    2016-02-27

    Kawasaki disease (KD) is a systemic vasculitis in infants that develops predominantly in the coronary arteries. Despite the clinically transient nature of active inflammation in childhood albeit rare complications (e.g., coronary artery aneurysm), KD has recently been suggested to increase the incidence of ischemic heart diseases in young adulthood. However, little is known about the histopathology of the coronary artery long after development of the acute KD vasculitis. To address this, we conducted histological studies of rabbit coronary arteries in adolescent phase after induction of the KD-like vasculitis induced by horse serum administration. After a transmural infiltration of inflammatory cells in acute phase at day 7, the artery exhibited a gradual decrease in the number of inflammatory cells and thickening of the intima during the chronic phase up to day 90, where proteoglycans were distinctly accumulated in the intima with abundant involvement of α-smooth muscle actin (α-SMA)-positive cells, most of which accompanied expression of VCAM-1 and NF-κB. Distinct from classical atherosclerosis, inflammatory cells, e.g., macrophages, were barely detected during the chronic phase. These observations indicate that the KD-like coronary arteritis is followed by intimal thickening via accumulation of proteoglycans and proliferation of α-SMA-positive cells, reflecting aberrant coronary artery remodeling. PMID:27006519

  1. hMTH1 expression protects mitochondria from Huntington's disease-like impairment

    PubMed Central

    Ventura, Ilenia; Russo, Maria Teresa; De Nuccio, Chiara; De Luca, Gabriele; Degan, Paolo; Bernardo, Antonietta; Visentin, Sergio; Minghetti, Luisa; Bignami, Margherita

    2013-01-01

    Huntington disease (HD) is a neurodegenerative disease caused by expansion of CAG repeats in the huntingtin (Htt) gene. The expression of hMTH1, the human hydrolase that degrades oxidized purine nucleoside triphosphates, grants protection in a chemical HD mouse model in which HD-like features are induced by the mitochondrial toxin 3-nitropropionic acid (3-NP). To further examine the relationship between oxidized dNTPs and HD-like neurodegeneration, we studied the effects of hMTH1 expression in a genetic cellular model for HD, such as striatal cells expressing mutant htt (HdhQ111). hMTH1 expression protected these cells from 3-NP and H2O2-induced killing, by counteracting the mutant htt-dependent increased vulnerability and accumulation of nuclear and mitochondrial DNA 8-hydroxyguanine levels. hMTH1 expression reverted the decreased mitochondrial membrane potential characteristic of HdhQ111 cells and delayed the increase in mitochondrial reactive oxygen species associated with 3-NP treatment. Further indications of hMTH1-mediated mitochondrial protection are the partial reversion of 3-NP-induced alterations in mitochondrial morphology and the modulation of DRP1 and MFN1 proteins, which control fusion/fission rates of mitochondria. Finally, in line with the in vitro findings, upon 3-NP in vivo treatment, 8-hydroxyguanine levels in mitochondrial DNA from heart, muscle and brain are significantly lower in transgenic hMTH1-expressing mice than in wild-type animals. PMID:22974734

  2. Amyloid accumulation is a late event in sporadic Alzheimer's disease-like pathology in nontransgenic rats

    PubMed Central

    Stefanova, Natalia A.; Muraleva, Natalia A.; Korbolina, Elena E.; Kiseleva, Elena; Maksimova, Kseniya Yi.; Kolosova, Nataliya G.

    2015-01-01

    The amyloid cascade hypothesis posits that deposition of the amyloid β (Aβ) peptide in the brain is a key event in the initiation of Alzheimer's disease (AD). Nonetheless, it now seems increasingly unlikely that amyloid toxicity is the cause of sporadic AD, which leads to cognitive decline. Here, using accelerated-senescence nontransgenic OXYS rats, we confirmed that aggregation of Aβ is a later event in AD-like pathology. We showed that an age-dependent increase in the levels of Aβ1–42 and extracellular Aβ deposits in the brain of OXYS rats occur later than do synaptic losses, neuronal cell death, mitochondrial structural abnormalities, and hyperphosphorylation of the tau protein. We identified the variants of the genes that are strongly associated with the risk of either late-onset or early-onset AD, including App, Apoe4, Bace1, Psen1, Psen2, and Picalm. We found that in OXYS rats nonsynonymous SNPs were located only in the genes Casp3 and Sorl1. Thus, we present proof that OXYS rats may be a model of sporadic AD. It is possible that multiple age-associated pathological processes may precede the toxic amyloid accumulation, which in turn triggers the final stage of the sporadic form of AD and becomes a hallmark event of the disease. PMID:25595891

  3. Neuroprotective effects of sulforaphane on cholinergic neurons in mice with Alzheimer's disease-like lesions.

    PubMed

    Zhang, Rui; Zhang, Jingzhu; Fang, Lingduo; Li, Xi; Zhao, Yue; Shi, Wanying; An, Li

    2014-01-01

    Alzheimer's disease (AD) is a common neurodegenerative disease in elderly individuals, and effective therapies are unavailable. This study was designed to investigate the neuroprotective effects of sulforaphane (an activator of NF-E2-related factor 2) on mice with AD-like lesions induced by combined administration of aluminum and D-galactose. Step-down-type passive avoidance tests showed sulforaphane ameliorated cognitive impairment in AD-like mice. Immunohistochemistry results indicated sulforaphane attenuated cholinergic neuron loss in the medial septal and hippocampal CA1 regions in AD-like mice. However, spectrophotometry revealed no significant difference in acetylcholine level or the activity of choline acetyltransferase or acetylcholinesterase in the cerebral cortex among groups of control and AD-like mice with and without sulforaphane treatment. Sulforaphane significantly increased the numbers of 5-bromo-2'-deoxyuridine-positive neurons in the subventricular and subgranular zones in AD-like mice which were significantly augmented compared with controls. Atomic absorption spectrometry revealed significantly lower aluminum levels in the brains of sulforaphane-treated AD-like mice than in those that did not receive sulforaphane treatment. In conclusion, sulforaphane ameliorates neurobehavioral deficits by reducing cholinergic neuron loss in the brains of AD-like mice, and the mechanism may be associated with neurogenesis and aluminum load reduction. These findings suggest that phytochemical sulforaphane has potential application in AD therapeutics. PMID:25196440

  4. Histopathological Characteristics of Post-inflamed Coronary Arteries in Kawasaki Disease-like Vasculitis of Rabbits

    PubMed Central

    Fujii, Maiko; Tanaka, Hideo; Nakamura, Akihiro; Suzuki, Chinatsu; Harada, Yoshinori; Takamatsu, Tetsuro; Hamaoka, Kenji

    2016-01-01

    Kawasaki disease (KD) is a systemic vasculitis in infants that develops predominantly in the coronary arteries. Despite the clinically transient nature of active inflammation in childhood albeit rare complications (e.g., coronary artery aneurysm), KD has recently been suggested to increase the incidence of ischemic heart diseases in young adulthood. However, little is known about the histopathology of the coronary artery long after development of the acute KD vasculitis. To address this, we conducted histological studies of rabbit coronary arteries in adolescent phase after induction of the KD-like vasculitis induced by horse serum administration. After a transmural infiltration of inflammatory cells in acute phase at day 7, the artery exhibited a gradual decrease in the number of inflammatory cells and thickening of the intima during the chronic phase up to day 90, where proteoglycans were distinctly accumulated in the intima with abundant involvement of α-smooth muscle actin (α-SMA)-positive cells, most of which accompanied expression of VCAM-1 and NF-κB. Distinct from classical atherosclerosis, inflammatory cells, e.g., macrophages, were barely detected during the chronic phase. These observations indicate that the KD-like coronary arteritis is followed by intimal thickening via accumulation of proteoglycans and proliferation of α-SMA-positive cells, reflecting aberrant coronary artery remodeling. PMID:27006519

  5. Loss of Polo ameliorates APP-induced Alzheimer’s disease-like symptoms in Drosophila

    PubMed Central

    Peng, Fei; Zhao, Yu; Huang, Xirui; Chen, Changyan; Sun, Lili; Zhuang, Luming; Xue, Lei

    2015-01-01

    The amyloid precursor protein (APP) has been implicated in the pathogenesis of Alzheimer’s disease (AD). Despite extensive studies, little is known about the regulation of APP’s functions in vivo. Here we report that expression of human APP in Drosophila, in the same temporal-spatial pattern as its homolog APPL, induced morphological defects in wings and larval NMJ, larva and adult locomotion dysfunctions, male choice disorder and lifespan shortening. To identify additional genes that modulate APP functions, we performed a genetic screen and found that loss of Polo, a key regulator of cell cycle, partially suppressed APP-induced morphological and behavioral defects in larval and adult stages. Finally, we showed that eye-specific expression of APP induced retina degeneration and cell cycle re-entry, both phenotypes were mildly ameliorated by loss of Polo. These results suggest Polo is an important in vivo regulator of the pathological functions of APP, and provide insight into the role of cell cycle re-entry in AD pathogenesis. PMID:26597721

  6. Houttuynia cordata Improves Cognitive Deficits in Cholinergic Dysfunction Alzheimer’s Disease-Like Models

    PubMed Central

    Huh, Eugene; Kim, Hyo Geun; Park, Hanbyeol; Kang, Min Seo; Lee, Bongyong; Oh, Myung Sook

    2014-01-01

    Cognitive impairment is a result of dementia of diverse causes, such as cholinergic dysfunction and Alzheimer’s disease (AD). Houttuynia cordata Thunb. (Saururaceae) has long been used as a traditional herbal medicine. It has biological activities including protective effects against amyloid beta (Aβ) toxicity, via regulation of calcium homeostasis, in rat hippocampal cells. To extend previous reports, we investigated the effects of water extracts of H. cordata herb (HCW) on tauopathies, also involving calcium influx. We then confirmed the effects of HCW in improving memory impairment and neuronal damage in mice with Aβ-induced neurotoxicity. We also investigated the effects of HCW against scopolamine-induced cholinergic dysfunction in mice. In primary neuronal cells, HCW inhibited the phosphorylation of tau by regulating p25/p35 expression in Aβ-induced neurotoxicity. In mice with Aβ-induced neurotoxicity, HCW improved cognitive impairment, as assessed with behavioral tasks, such as novel object recognition, Y-maze, and passive avoidance tasks. HCW also inhibited the degeneration of neurons in the CA3 region of the hippocampus in Aβ-induced neurotoxicity. Moreover, HCW, which had an IC50 value of 79.7 μg/ml for acetylcholinesterase inhibition, ameliorated scopolamine-induced cognitive impairment significantly in Y-maze and passive avoidance tasks. These results indicate that HCW improved cognitive impairment, due to cholinergic dysfunction, with inhibitory effects against tauopathies and cholinergic antagonists, suggesting that HCW may be an interesting candidate to investigate for the treatment of AD. PMID:25009697

  7. Houttuynia cordata Improves Cognitive Deficits in Cholinergic Dysfunction Alzheimer's Disease-Like Models.

    PubMed

    Huh, Eugene; Kim, Hyo Geun; Park, Hanbyeol; Kang, Min Seo; Lee, Bongyong; Oh, Myung Sook

    2014-05-01

    Cognitive impairment is a result of dementia of diverse causes, such as cholinergic dysfunction and Alzheimer's disease (AD). Houttuynia cordata Thunb. (Saururaceae) has long been used as a traditional herbal medicine. It has biological activities including protective effects against amyloid beta (Aβ) toxicity, via regulation of calcium homeostasis, in rat hippocampal cells. To extend previous reports, we investigated the effects of water extracts of H. cordata herb (HCW) on tauopathies, also involving calcium influx. We then confirmed the effects of HCW in improving memory impairment and neuronal damage in mice with Aβ-induced neurotoxicity. We also investigated the effects of HCW against scopolamine-induced cholinergic dysfunction in mice. In primary neuronal cells, HCW inhibited the phosphorylation of tau by regulating p25/p35 expression in Aβ-induced neurotoxicity. In mice with Aβ-induced neurotoxicity, HCW improved cognitive impairment, as assessed with behavioral tasks, such as novel object recognition, Y-maze, and passive avoidance tasks. HCW also inhibited the degeneration of neurons in the CA3 region of the hippocampus in Aβ-induced neurotoxicity. Moreover, HCW, which had an IC50 value of 79.7 μg/ml for acetylcholinesterase inhibition, ameliorated scopolamine-induced cognitive impairment significantly in Y-maze and passive avoidance tasks. These results indicate that HCW improved cognitive impairment, due to cholinergic dysfunction, with inhibitory effects against tauopathies and cholinergic antagonists, suggesting that HCW may be an interesting candidate to investigate for the treatment of AD. PMID:25009697

  8. Impact of peripheral myeloid cells on amyloid-β pathology in Alzheimer's disease-like mice.

    PubMed

    Prokop, Stefan; Miller, Kelly R; Drost, Natalia; Handrick, Susann; Mathur, Vidhu; Luo, Jian; Wegner, Anja; Wyss-Coray, Tony; Heppner, Frank L

    2015-10-19

    Although central nervous system-resident microglia are believed to be ineffective at phagocytosing and clearing amyloid-β (Aβ), a major pathological hallmark of Alzheimer's disease (AD), it has been suggested that peripheral myeloid cells constitute a heterogeneous cell population with greater Aβ-clearing capabilities. Here, we demonstrate that the conditional ablation of resident microglia in CD11b-HSVTK (TK) mice is followed by a rapid repopulation of the brain by peripherally derived myeloid cells. We used this system to directly assess the ability of peripheral macrophages to reduce Aβ plaque pathology and therefore depleted and replaced the pool of resident microglia with peripherally derived myeloid cells in Aβ-carrying APPPS1 mice crossed to TK mice (APPPS1;TK). Despite a nearly complete exchange of resident microglia with peripheral myeloid cells, there was no significant change in Aβ burden or APP processing in APPPS1;TK mice. Importantly, however, newly recruited peripheral myeloid cells failed to cluster around Aβ deposits. Even additional anti-Aβ antibody treatment aimed at engaging myeloid cells with amyloid plaques neither directed peripherally derived myeloid cells to amyloid plaques nor altered Aβ burden. These data demonstrate that mere recruitment of peripheral myeloid cells to the brain is insufficient in substantially clearing Aβ burden and suggest that specific additional triggers appear to be required to exploit the full potential of myeloid cell-based therapies for AD. PMID:26458768

  9. Treadmill exercise prevents learning and memory impairment in Alzheimer's disease-like pathology.

    PubMed

    Dao, An T; Zagaar, Munder A; Levine, Amber T; Salim, Samina; Eriksen, Jason L; Alkadhi, Karim A

    2013-06-01

    Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by progressive memory loss. In contrast, accumulating evidence suggests a neuroprotective role of regular exercise in aging associated memory impairment. In this study, we investigated the ability of regular exercise to prevent impairments of short-term memory (STM) and early long-term potentiation (E-LTP) in area CA1 of the hippocampus in a rat model of AD (i.c.v. infusion of 250 pmol/day Aβ1-42 peptides). We utilized behavioral assessment, in vivo electrophysiological recording, and immunoblotting in 4 groups of adult Wistar rats: control, treadmill exercise (Ex), β-amyloid-infused (Aβ), and amyloid-infused/treadmill exercised (Ex/Aβ). Our findings indicated that Aβ rats made significantly more errors in the radial arm water maze (RAWM) compared to all other groups and exhibited suppressed E-LTP in area CA1, which correlated with deleterious alterations in the levels of memory and E-LTP-related signaling molecules including calcineurin (PP2B), brain derivedneurotrophic factor (BDNF) and phosphorylated CaMKII (p-CaMKII). Compared to controls, Ex and Ex/Aβ rats showed a similar behavioral performance and a normal E-LTP with no detrimental changes in the levels of PP2B, BDNF, and p- CaMKII. We conclude that treadmill exercise maybe able to prevent cognitive impairment associated with AD pathology. PMID:23627709

  10. Stress acts cumulatively to precipitate Alzheimer's disease-like tau pathology and cognitive deficits.

    PubMed

    Sotiropoulos, Ioannis; Catania, Caterina; Pinto, Lucilia G; Silva, Rui; Pollerberg, G Elizabeth; Takashima, Akihiko; Sousa, Nuno; Almeida, Osborne F X

    2011-05-25

    Stressful life experiences are likely etiological factors in sporadic forms of Alzheimer's disease (AD). Many AD patients hypersecrete glucocorticoids (GCs), and their GC levels correlate with the rate of cognitive impairment and extent of neuronal atrophy. Severity of cognitive deficits in AD correlates strongly with levels of hyperphosphorylated forms of the cytoskeletal protein TAU, an essential mediator of the actions of amyloid β (Aβ), another molecule with a key pathogenic role in AD. Our objective was to investigate the sequential interrelationships between these various pathogenic elements, in particular with respect to the mechanisms through which stress might precipitate cognitive decline. We thus examined whether stress, through the mediation of GCs, influences TAU hyperphosphorylation, a critical and early event in the cascade of processes leading to AD pathology. Results from healthy, wild-type, middle-aged rats show that chronic stress and GC induce abnormal hyperphosphorylation of TAU in the hippocampus and prefrontal cortex (PFC), with contemporaneous impairments of hippocampus- and PFC-dependent behaviors. Exogenous GC potentiated the ability of centrally infused Aβ to induce hyperphosphorylation of TAU epitopes associated with AD and cytoplasmic accumulation of TAU, while previous exposure to stress aggravated the biochemical and behavioral effects of GC in Aβ-infused animals. Thus, lifetime stress/GC exposure may have a cumulative impact on the onset and progress of AD pathology, with TAU hyperphosphorylation serving to transduce the negative effects of stress and GC on cognition. PMID:21613497

  11. Choroid plexus implants rescue Alzheimer's disease-like pathologies by modulating amyloid-β degradation.

    PubMed

    Bolos, Marta; Antequera, Desireé; Aldudo, Jesús; Kristen, Henrike; Bullido, María Jesús; Carro, Eva

    2014-08-01

    The choroid plexuses (CP) release numerous biologically active enzymes and neurotrophic factors, and contain a subpopulation of neural progenitor cells providing the capacity to proliferate and differentiate into other types of cells. These characteristics make CP epithelial cells (CPECs) excellent candidates for cell therapy aiming at restoring brain tissue in neurodegenerative illnesses, including Alzheimer's disease (AD). In the present study, using in vitro approaches, we demonstrated that CP were able to diminish amyloid-β (Aβ) levels in cell cultures, reducing Aβ-induced neurotoxicity. For in vivo studies, CPECs were transplanted into the brain of the APP/PS1 murine model of AD that exhibits advanced Aβ accumulation and memory impairment. Brain examination after cell implantation revealed a significant reduction in brain Aβ deposits, hyperphosphorylation of tau, and astrocytic reactivity. Remarkably, the transplantation of CPECs was accompanied by a total behavioral recovery in APP/PS1 mice, improving spatial and non-spatial memory. These findings reinforce the neuroprotective potential of CPECs and the use of cell therapies as useful tools in AD. PMID:24343520

  12. IL-33 ameliorates Alzheimer's disease-like pathology and cognitive decline.

    PubMed

    Fu, Amy K Y; Hung, Kwok-Wang; Yuen, Michael Y F; Zhou, Xiaopu; Mak, Deejay S Y; Chan, Ivy C W; Cheung, Tom H; Zhang, Baorong; Fu, Wing-Yu; Liew, Foo Y; Ip, Nancy Y

    2016-05-10

    Alzheimer's disease (AD) is a devastating condition with no known effective treatment. AD is characterized by memory loss as well as impaired locomotor ability, reasoning, and judgment. Emerging evidence suggests that the innate immune response plays a major role in the pathogenesis of AD. In AD, the accumulation of β-amyloid (Aβ) in the brain perturbs physiological functions of the brain, including synaptic and neuronal dysfunction, microglial activation, and neuronal loss. Serum levels of soluble ST2 (sST2), a decoy receptor for interleukin (IL)-33, increase in patients with mild cognitive impairment, suggesting that impaired IL-33/ST2 signaling may contribute to the pathogenesis of AD. Therefore, we investigated the potential therapeutic role of IL-33 in AD, using transgenic mouse models. Here we report that IL-33 administration reverses synaptic plasticity impairment and memory deficits in APP/PS1 mice. IL-33 administration reduces soluble Aβ levels and amyloid plaque deposition by promoting the recruitment and Aβ phagocytic activity of microglia; this is mediated by ST2/p38 signaling activation. Furthermore, IL-33 injection modulates the innate immune response by polarizing microglia/macrophages toward an antiinflammatory phenotype and reducing the expression of proinflammatory genes, including IL-1β, IL-6, and NLRP3, in the cortices of APP/PS1 mice. Collectively, our results demonstrate a potential therapeutic role for IL-33 in AD. PMID:27091974

  13. Functional modulation of G-protein coupled receptors during Parkinson disease-like neurodegeneration.

    PubMed

    Jenkins, Bruce G; Zhu, Aijun; Poutiainen, Pekka; Choi, Ji-Kyung; Kil, Kun-Eek; Zhang, Zhaoda; Kuruppu, Darshini; Aytan, Nurgul; Dedeoglu, Alpaslan; Brownell, Anna-Liisa

    2016-09-01

    G-protein coupled dopamine and metabotropic glutamate receptors (mGlu) can modulate neurotransmission during Parkinson's disease (PD)-like neurodegeneration. PET imaging studies in a unilateral dopamine denervation model (6-OHDA) showed a significant inverse correlation of presynaptic mGlu4 and postsynaptic mGlu5 expression in the striatum and rapidly declining mGlu4 and enhanced mGlu5 expression in the hippocampus during progressive degeneration over time. Immunohistochemical studies verified the decreased mGlu4 expression in the hippocampus on the lesion side but did not show difference in mGlu5 expression between lesion and control side. Pharmacological MRI studies showed enhanced hemodynamic response in several brain areas on the lesion side compared to the control side after challenge with mGlu4 positive allosteric modulator or mGlu5 negative allosteric modulator. However, mGlu4 response was biphasic having short enhancement followed by negative response on both sides of brain. Studies in mGlu4 expressing cells demonstrated that glutamate induces cooperative increase in binding of mGlu4 ligands - especially at high glutamate levels consistent with in vivo concentration. This suggests that mGlu allosteric modulators as drug candidates will be highly sensitive to changes in glutamate concentration and hence metabolic state. These experiments demonstrate the importance of the longitudinal imaging studies to investigate temporal changes in receptor functions to obtain individual response for experimental drugs. PMID:26581500

  14. IL-33 ameliorates Alzheimer’s disease-like pathology and cognitive decline

    PubMed Central

    Fu, Amy K. Y.; Hung, Kwok-Wang; Yuen, Michael Y. F.; Zhou, Xiaopu; Mak, Deejay S. Y.; Chan, Ivy C. W.; Cheung, Tom H.; Zhang, Baorong; Fu, Wing-Yu; Liew, Foo Y.; Ip, Nancy Y.

    2016-01-01

    Alzheimer’s disease (AD) is a devastating condition with no known effective treatment. AD is characterized by memory loss as well as impaired locomotor ability, reasoning, and judgment. Emerging evidence suggests that the innate immune response plays a major role in the pathogenesis of AD. In AD, the accumulation of β-amyloid (Aβ) in the brain perturbs physiological functions of the brain, including synaptic and neuronal dysfunction, microglial activation, and neuronal loss. Serum levels of soluble ST2 (sST2), a decoy receptor for interleukin (IL)-33, increase in patients with mild cognitive impairment, suggesting that impaired IL-33/ST2 signaling may contribute to the pathogenesis of AD. Therefore, we investigated the potential therapeutic role of IL-33 in AD, using transgenic mouse models. Here we report that IL-33 administration reverses synaptic plasticity impairment and memory deficits in APP/PS1 mice. IL-33 administration reduces soluble Aβ levels and amyloid plaque deposition by promoting the recruitment and Aβ phagocytic activity of microglia; this is mediated by ST2/p38 signaling activation. Furthermore, IL-33 injection modulates the innate immune response by polarizing microglia/macrophages toward an antiinflammatory phenotype and reducing the expression of proinflammatory genes, including IL-1β, IL-6, and NLRP3, in the cortices of APP/PS1 mice. Collectively, our results demonstrate a potential therapeutic role for IL-33 in AD. PMID:27091974

  15. Depletion of the IKBKAP ortholog in zebrafish leads to hirschsprung disease-like phenotype

    PubMed Central

    Cheng, William Wai-Chun; Tang, Clara Sze-Man; Gui, Hong-Sheng; So, Man-Ting; Lui, Vincent Chi-Hang; Tam, Paul Kwong-Hang; Garcia-Barcelo, Maria-Mercè

    2015-01-01

    AIM: To investigate the role of IKBKAP (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase complex-associated protein) in the development of enteric nervous system (ENS) and Hirschsprung disease (HSCR). METHODS: In this study, we injected a morpholino that blocked the translation of ikbkap protein to 1-cell stage zebrafish embryos. The phenotype in the ENS was analysed by antibody staining of the pan-neuronal marker HuC/D followed by enteric neuron counting. The mean numbers of enteric neurons were compared between the morphant and the control. We also studied the expressions of ret and phox2bb, which are involved in ENS development, in the ikbkap morpholino injected embryos by quantitative reverse transcriptase polymerase chain reaction and compared them with the control. RESULTS: We observed aganglionosis (χ2, P < 0.01) and a reduced number of enteric neurons (38.8 ± 9.9 vs 50.2 ± 17.3, P < 0.05) in the zebrafish embryos injected with ikbkap translation-blocking morpholino (morphant) when compared with the control embryos. Specificity of the morpholino was confirmed by similar results obtained using a second non-overlapping morpholino that blocked the translation of ikbkap. We further studied the morphant by analysing the expression levels of genes involved in ENS development such as ret, phox2bb and sox10, and found that phox2bb, the ortholog of human PHOX2B, was significantly down-regulated (0.51 ± 0.15 vs 1.00 ± 0, P < 0.05). Although we also observed a reduction in the expression of ret, the difference was not significant. CONCLUSION: Loss of IKBKAP contributed to HSCR as demonstrated by functional analysis in zebrafish embryos. PMID:25717236

  16. Parkinson's disease-like forelimb akinesia induced by BmK I, a sodium channel modulator.

    PubMed

    Zhu, Hongyan; Wang, Ziyi; Jin, Jiahui; Pei, Xiao; Zhao, Yuxiao; Wu, Hao; Lin, Weide; Tao, Jie; Ji, Yonghua

    2016-07-15

    Parkinson's disease (PD) is a neurodegenerative disorder and characterized by motor disabilities which are mostly linked with high levels of synchronous oscillations in the basal ganglia neurons. Voltage-gated sodium channels (VGSCs) play a vital role in the abnormal electrical activity of neurons in the globus pallidus (GP) and the subthalamic nucleus (STN) in PD. BmK I, a α-like toxin purified from the Chinese scorpion Buthus martensi Karsch, has been identified a site-3-specific modulator of VGSCs. The present study shows that forelimb akinesia can be induced by the injection of BmK I into the globus pallidus (GP) in rats. In addition, BmK I cannot produce neuronal damage in vivo and in vitro at 24h after treatment, indicating that the forelimb akinesia does not result from neuronal damage. Electrophysiological studies further revealed that the inactivated Na(+) currents were showed to be more vulnerably modulated by BmK I than the activated Na(+) currents in human neuron-like SHSY5Y cells. Furthermore, the modulation of BmK I on inactivation was preferentially attributed to fast inactivation rather than slow inactivation. Therefore, the PD-like forelimb akinesia may result from the modulation of sodium channels in neuron by BmK I. These findings not only suggest that BmK I may be an effective and novel molecule for the study of pathogenesis in PD but also support the idea that VGSCs play a crucial role in the motor disabilities in PD. PMID:27108049

  17. HIV-1 Tat Contributes to Alzheimer's Disease-like Pathology in PSAPP Mice

    PubMed Central

    Giunta, Brian; Hou, Houyan; Zhu, Yuyan; Rrapo, Elona; Tian, Jun; Takashi, Mori; Commins, Deborah; Singer, Elyse; He, Johnny; Fernandez, Francisco; Tan, Jun

    2009-01-01

    Prevalence of HIV-associated cognitive impairment is rising. Amyloid-beta (A-beta) plaque deposition in the brain may be a contributing factor as epidemiological data suggests significant numbers of long-term HIV survivors are at elevated risk of developing Alzheimer's disease (AD). HIV-1 Tat-induced A-beta deposition, tau phosphorylation, and subsequent neuronal death could be risk factors for subsequent AD and/or HIV-related cognitive impairment. To mimic this clinical condition, we generated mice with HIV-1 Tat-induced AD-like pathology. We first performed a short-term Doxycycline (dox) dosing (54, 108, and 216 mg/kg/day) study in transgenic mice whose astrocytes express HIV-1 Tat via activation of a GFAP/dox-inducible promoter. After one week, mouse brains were examined histologically and the expression of Bcl-xL, Bax, and phospho-tau was investigated by Western blotting. We next cross-bred these mice with the PSAPP mouse model of AD. To simulate chronic Tat secretion over periods longer than one week, we used an optimized dose of 54 mg/kg/day on a biweekly basis over three months; based on the initial dose ranging study in the Tat transgenic mice. This was followed by antisera detection of A-beta, and Western blot for phospho-tau, Bcl-xL, and Bax. Tat significantly induced neuron degeneration and tau phosphorylation in Tat transgenic mice, dox dependently (P<0.001) with the most robust effects at the 216 mg/kg/day dose. In the long term study, similar effects at the chronic 54 mg/kg/day dose were observed in PSAPP/Tat mice induced with dox. These mice also showed significantly more A-beta deposition (P < 0.05), neurodegeneration, neuronal apoptotic signaling, and phospho-tau than PSAPP mice (P < 0.05). In conclusion, HIV-1 Tat significantly promotes AD-like pathology in PSAPP/Tat mice. This model may provide a framework in which to identify new mechanisms involved in cognitive impairment in the HIV infected population, and possible treatments. Additional works

  18. Exploring the Role of Microorganisms in the Disease-Like Syndrome Affecting the Sponge Ianthella basta▿ †

    PubMed Central

    Luter, Heidi M.; Whalan, Steve; Webster, Nicole S.

    2010-01-01

    A disease-like syndrome is currently affecting a large percentage of the Ianthella basta populations from the Great Barrier Reef and central Torres Strait. Symptoms of the syndrome include discolored, necrotic spots leading to tissue degradation, exposure of the skeletal fibers, and disruption of the choanocyte chambers. To ascertain the role of microbes in the disease process, a comprehensive comparison of bacteria, viruses, fungi, and other eukaryotes was performed in healthy and diseased sponges using multiple techniques. A low diversity of microbes was observed in both healthy and diseased sponge communities, with all sponges dominated by an Alphaproteobacteria, a Gammaproteobacteria, and a group I crenarchaeota. Bacterial cultivation, community analysis by denaturing gradient gel electrophoresis (Bacteria and Eukarya), sequencing of 16S rRNA clone libraries (Bacteria and Archaea), and direct visual assessment by electron microscopy failed to reveal any putative pathogens. In addition, infection assays could not establish the syndrome in healthy sponges even after direct physical contact with affected tissue. These results suggest that microbes are not responsible for the formation of brown spot lesions and necrosis in I. basta. PMID:20622129

  19. Chronic exposure to low benzo[a]pyrene level causes neurodegenerative disease-like syndromes in zebrafish (Danio rerio).

    PubMed

    Gao, Dongxu; Wu, Meifang; Wang, Chonggang; Wang, Yuanchuan; Zuo, Zhenghong

    2015-10-01

    Previous epidemiological and animal studies report that exposure to environmental pollutant exposure links to neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. Benzo[a]pyrene (BaP), a neurotoxic polycyclic aromatic hydrocarbon, has been increasingly released into the environment during recent decades. So far, the role of BaP on the development of neurodegenerative diseases remaind unclear. This study aimed to determine whether chronic exposure to low dose BaP would cause neurodegenerative disease-like syndromes in zebrafish (Danio rerio). We exposed zebrafish, from early embryogenesis to adults, to environmentally relevant concentrations of BaP for 230 days. Our results indicated that BaP decreased the brain weight to body weight ratio, locomotor activity and cognitive ability; induced the loss of dopaminergic neurons; and resulted in neurodegeneration. In addition, obvious cell apoptosis in the brain was found. Furthermore, the neurotransmitter levels of dopamine and 3,4-dihydroxyphenylacetic acid, the mRNA levels of the genes encoding dopamine transporter, Parkinson protein 7, phosphatase and tensin-induced putative kinase 1, ubiquitin carboxy-terminal hydrolase L1, leucine-rich repeat serine/threonine kinase 2, amyloid precursor protein b, presenilin 1 and presenilin 2 were significantly down-regulated by BaP exposure. These findings suggest that chronic exposure to low dose BaP could cause the behavioral, neuropathological, neurochemical, and genetic features of neurodegenerative diseases. This study provides clues that BaP may constitute an important environmental risk factor for neurodegenerative diseases in humans. PMID:26349946

  20. Benzyl-N-acetyl-alpha-D-galactosaminide induces a storage disease-like phenotype by perturbing the endocytic pathway.

    PubMed

    Ulloa, Fausto; Real, Francisco X

    2003-04-01

    The sugar analog O-benzyl-N-acetyl-alpha-d-galactosaminide (BG) is an inhibitor of glycan chain elongation and inhibits alpha2,3-sialylation in mucus-secreting HT-29 cells. Long-term exposure of these cells to BG is associated with the accumulation of apical glycoproteins in cytoplasmic vesicles. The mechanisms involved therein and the nature of the vesicles have not been elucidated. In these cells, a massive amount of BG metabolites is synthesized. Because sialic acid is mainly distributed apically in epithelial cells, it has been proposed that the BG-induced undersialylation of apical membrane glycoproteins is responsible for their intracellular accumulation due to a defect in anterograde traffic and that sialic acid may constitute an apical targeting signal. In this work, we demonstrate that the intracellular accumulation of membrane glycoproteins does not result mainly from defects in anterograde traffic. By contrast, in BG-treated cells, endocytosed membrane proteins were retained intracellularly for longer periods of time than in control cells and colocalized with accumulated MUC1 and beta(1) integrin in Rab7/lysobisphosphatidic acid(+) vesicles displaying features of late endosomes. The phenotype of BG-treated cells is reminiscent of that observed in lysosomal storage disorders. Sucrose induced a BG-like, lysosomal storage disease-like phenotype without affecting sialylation, indicating that undersialylation is not a requisite for the intracellular accumulation of membrane glycoproteins. Our findings strongly support the notion that the effects observed in BG-treated cells result from the accumulation of BG-derived metabolites and from defects in the endosomal pathway. We propose that abnormal subcellular distribution of membrane glycoproteins involved in cellular communication and/or signaling may also take place in lysosomal storage disorders and may contribute to their pathogenesis. PMID:12538583

  1. Junctophilin 3 (JPH3) expansion mutations causing Huntington disease like 2 (HDL2) are common in South African patients with African ancestry and a Huntington disease phenotype.

    PubMed

    Krause, Amanda; Mitchell, Claire; Essop, Fahmida; Tager, Susan; Temlett, James; Stevanin, Giovanni; Ross, Christopher; Rudnicki, Dobrila; Margolis, Russell

    2015-10-01

    Huntington disease (HD) is a progressive autosomal dominant neurodegenerative disorder, characterized by abnormal movements, cognitive decline, and psychiatric symptoms, caused by a CAG repeat expansion in the huntingtin (HTT) gene on chromosome 4p. A CAG/CTG repeat expansion in the junctophilin-3 (JPH3) gene on chromosome 16q24.2 causes a Huntington disease-like phenotype (HDL2). All patients to date with HDL2 have some African ancestry. The present study aimed to characterize the genetic basis of the Huntington disease phenotype in South Africans and to investigate the possible origin of the JPH3 mutation. In a sample of unrelated South African individuals referred for diagnostic HD testing, 62% (106/171) of white patients compared to only 36% (47/130) of black patients had an expansion in HTT. However, 15% (20/130) of black South African patients and no white patients (0/171) had an expansion in JPH3, confirming the diagnosis of Huntington disease like 2 (HDL2). Individuals with HDL2 share many clinical features with individuals with HD and are clinically indistinguishable in many cases, although the average age of onset and diagnosis in HDL2 is 5 years later than HD and individual clinical features may be more prominent. HDL2 mutations contribute significantly to the HD phenotype in South Africans with African ancestry. JPH3 haplotype studies in 31 families, mainly from South Africa and North America, provide evidence for a founder mutation and support a common African origin for all HDL2 patients. Molecular testing in individuals with an HD phenotype and African ancestry should include testing routinely for JPH3 mutations. PMID:26079385

  2. Structures of three polycystic kidney disease-like domains from Clostridium histolyticum collagenases ColG and ColH.

    PubMed

    Bauer, Ryan; Janowska, Katarzyna; Taylor, Kelly; Jordan, Brad; Gann, Steve; Janowski, Tomasz; Latimer, Ethan C; Matsushita, Osamu; Sakon, Joshua

    2015-03-01

    Clostridium histolyticum collagenases ColG and ColH are segmental enzymes that are thought to be activated by Ca(2+)-triggered domain reorientation to cause extensive tissue destruction. The collagenases consist of a collagenase module (s1), a variable number of polycystic kidney disease-like (PKD-like) domains (s2a and s2b in ColH and s2 in ColG) and a variable number of collagen-binding domains (s3 in ColH and s3a and s3b in ColG). The X-ray crystal structures of Ca(2+)-bound holo s2b (1.4 Å resolution, R = 15.0%, Rfree = 19.1%) and holo s2a (1.9 Å resolution, R = 16.3%, Rfree = 20.7%), as well as of Ca(2+)-free apo s2a (1.8 Å resolution, R = 20.7%, Rfree = 27.2%) and two new forms of N-terminally truncated apo s2 (1.4 Å resolution, R = 16.9%, Rfree = 21.2%; 1.6 Å resolution, R = 16.2%, Rfree = 19.2%), are reported. The structurally similar PKD-like domains resemble the V-set Ig fold. In addition to a conserved β-bulge, the PKD-like domains feature a second bulge that also changes the allegiance of the subsequent β-strand. This β-bulge and the genesis of a Ca(2+) pocket in the archaeal PKD-like domain suggest a close kinship between bacterial and archaeal PKD-like domains. Different surface properties and indications of different dynamics suggest unique roles for the PKD-like domains in ColG and in ColH. Surface aromatic residues found on ColH s2a-s2b, but not on ColG s2, may provide the weak interaction in the biphasic collagen-binding mode previously found in s2b-s3. B-factor analyses suggest that in the presence of Ca(2+) the midsection of s2 becomes more flexible but the midsections of s2a and s2b stay rigid. The different surface properties and dynamics of the domains suggest that the PKD-like domains of M9B bacterial collagenase can be grouped into either a ColG subset or a ColH subset. The conserved properties of PKD-like domains in ColG and in ColH include Ca(2+) binding. Conserved residues not only interact with Ca(2+), but also

  3. Ultra-trace graphene oxide in a water environment triggers Parkinson's disease-like symptoms and metabolic disturbance in zebrafish larvae.

    PubMed

    Ren, Chaoxiu; Hu, Xiangang; Li, Xueyan; Zhou, Qixing

    2016-07-01

    Over the past decade, the safety of nanomaterials has attracted attention due to their rapid development. The relevant health threat of these materials remains largely unknown, particularly at environmentally or biologically relevant ultra-trace concentrations. To address this, we first found that graphene oxide (GO, a carbon nanomaterial that receives extensive attention across various disciplines) at concentrations of 0.01 μg/L-1 μg/L induced Parkinson's disease-like symptoms in zebrafish larvae. In this model, zebrafish showed a loss of more than 90% of dopamine neurons, a 69-522% increase in Lewy bodies (α-synuclein and ubiquitin) and significantly disturbed locomotive activity. Moreover, it was also shown that GO was able to translocate from the water environment to the brain and localize to the nucleus of the diencephalon, thereby inducing structural and morphological damage in the mitochondria. Cell apoptosis and senescence were triggered via oxidative stress, as shown by the upregulation of caspase 8 and β-galactosidase. Using metabolomics, we found that the upregulation of amino acid and some fatty acids (e.g. dodecanoic acid, hexadecanoic acid, octadecenoic acid, nonanoic acid, arachidonic acid, eicosanoic acid, propanoic acid and benzenedicarboxylic acid) metabolism and the downregulation of some other fatty acids (e.g. butanoic acid, phthalic acid and docosenoic acid) are linked to these Parkinson's disease-like symptoms. These findings broaden our understanding of nanomaterial safety at ultra-trace concentrations. PMID:27085073

  4. Legg-Perthes disease-like joint involvement and diagnosis delay in Scheie syndrome: a case report.

    PubMed

    Melikoglu, Meltem Alkan; Kocabas, Hilal; Sezer, Ilhan; Cay, Hasan Fatih; Cassidy, Aysegul Guller; Balci, Nilufer

    2007-11-01

    Mucopolysaccharidosis (MPS) type I is an inherited disease caused by the absence or malfunctioning of lysosomal enzymes. Three subtypes, based on severity of symptoms, were described, and Scheie syndrome (also called MPS I S) is the mildest form. Although there may be some typical extra-articular manifestations, musculoskeletal involvement may be the only presenting sign in the absence of other symptoms in the patients with less severe forms. The patients with MPS I S, especially in attenuated phenotypes, may be sometimes difficult to recognize for physicians not familiar with the disease. With this case presentation, it is aimed to draw attention to this disease, which could be delayed for the correct diagnosis. An increased awareness of the disease may contribute to more accurate diagnosis, and patients may benefit from early intervention. PMID:17264973

  5. The SAMP1/YitFc Mouse Strain: A Spontaneous Model of Crohn’s Disease-Like Ileitis

    PubMed Central

    Pizarro, Theresa T.; Pastorelli, Luca; Bamias, Giorgos; Garg, Rekha R.; Reuter, Brian K.; Mercado, Joseph R.; Chieppa, Marcello; Arseneau, Kristen O; Ley, Klaus; Cominelli, Fabio

    2011-01-01

    The SAMP1/YitFc mouse strain represents a model of Crohn’s disease (CD)-like ileitis that is ideal for investigating the pathogenesis of chronic intestinal inflammation. Differently from the vast majority of animal models of colitis, the ileal-specific phenotype characteristic of SAMP1/YitFc mice occurs spontaneously, without genetic, chemical or immunological manipulation. In addition, SAMP1/YitFc mice possess remarkable similarities to the human condition in regard to disease location, histologic features, incidence of extra-intestinal manifestations, and response to conventional therapies. SAMP1/YitFc mice also display a well-defined time course of a pre-disease state, and phases of acute and chronic ileitis. As such, the SAMP1/YitFc model is particularly suitable for elucidating pathways that precede the clinical phenotype that may lead to preventive, and therefore more efficacious, intervention with the natural course of disease, or alternatively, for the development of therapeutic strategies directed against chronic, established ileitis. In the following review, we summarize important contributions made by our group and others that uncover potential mechanisms in the pathogenesis of CD using this unique murine model of chronic intestinal inflammation. PMID:21557393

  6. Lack of Neuronal IFN-β-IFNAR Causes Lewy Body- and Parkinson’s Disease-like Dementia

    PubMed Central

    Ejlerskov, Patrick; Hultberg, Jeanette Göransdotter; Wang, JunYang; Carlsson, Robert; Ambjørn, Malene; Kuss, Martin; Liu, Yawei; Porcu, Giovanna; Kolkova, Kateryna; Friis Rundsten, Carsten; Ruscher, Karsten; Pakkenberg, Bente; Goldmann, Tobias; Loreth, Desiree; Prinz, Marco; Rubinsztein, David C.; Issazadeh-Navikas, Shohreh

    2015-01-01

    Summary Neurodegenerative diseases have been linked to inflammation, but whether altered immunomodulation plays a causative role in neurodegeneration is not clear. We show that lack of cytokine interferon-β (IFN-β) signaling causes spontaneous neurodegeneration in the absence of neurodegenerative disease-causing mutant proteins. Mice lacking Ifnb function exhibited motor and cognitive learning impairments with accompanying α-synuclein-containing Lewy bodies in the brain, as well as a reduction in dopaminergic neurons and defective dopamine signaling in the nigrostriatal region. Lack of IFN-β signaling caused defects in neuronal autophagy prior to α-synucleinopathy, which was associated with accumulation of senescent mitochondria. Recombinant IFN-β promoted neurite growth and branching, autophagy flux, and α-synuclein degradation in neurons. In addition, lentiviral IFN-β overexpression prevented dopaminergic neuron loss in a familial Parkinson’s disease model. These results indicate a protective role for IFN-β in neuronal homeostasis and validate Ifnb mutant mice as a model for sporadic Lewy body and Parkinson’s disease dementia. PMID:26451483

  7. Epitope and isotype specificities of antibodies to -amyloid peptide for protection against Alzheimer's disease-like neuropathology

    NASA Astrophysics Data System (ADS)

    Bard, Frédérique; Barbour, Robin; Cannon, Catherine; Carretto, Robert; Fox, Michael; Games, Dora; Guido, Teresa; Hoenow, Kathleen; Hu, Kang; Johnson-Wood, Kelly; Khan, Karen; Kholodenko, Dora; Lee, Celeste; Lee, Mike; Motter, Ruth; Nguyen, Minh; Reed, Amanda; Schenk, Dale; Tang, Pearl; Vasquez, Nicki; Seubert, Peter; Yednock, Ted

    2003-02-01

    Transgenic PDAPP mice, which express a disease-linked isoform of the human amyloid precursor protein, exhibit CNS pathology that is similar to Alzheimer's disease. In an age-dependent fashion, the mice develop plaques containing -amyloid peptide (A) and exhibit neuronal dystrophy and synaptic loss. It has been shown in previous studies that pathology can be prevented and even reversed by immunization of the mice with the A peptide. Similar protection could be achieved by passive administration of some but not all monoclonal antibodies against A. In the current studies we sought to define the optimal antibody response for reducing neuropathology. Immune sera with reactivity against different A epitopes and monoclonal antibodies with different isotypes were examined for efficacy both ex vivo and in vivo. The studies showed that: (i) of the purified or elicited antibodies tested, only antibodies against the N-terminal regions of A were able to invoke plaque clearance; (ii) plaque binding correlated with a clearance response and neuronal protection, whereas the ability of antibodies to capture soluble A was not necessarily correlated with efficacy; (iii) the isotype of the antibody dramatically influenced the degree of plaque clearance and neuronal protection; (iv) high affinity of the antibody for Fc receptors on microglial cells seemed more important than high affinity for Aβ itself; and (v) complement activation was not required for plaque clearance. These results indicate that antibody Fc-mediated plaque clearance is a highly efficient and effective process for protection against neuropathology in an animal model of Alzheimer's disease.

  8. Ménétrier's disease-like hypertrophic gastritis in two red-capped mangabeys (Cercocebus torquatus).

    PubMed

    Emerson, Jessica A; Adkesson, Michael J; Colegrove, Kathleen M; Burdick, Stacy K; Langan, Jennifer N

    2014-01-01

    Chronic lymphoplasmacytic gastritis in two red-capped mangabeys (Cercocebus torquatus) at a zoological facility progressed to severe hypertrophic gastropathy similar to Ménétrier's disease that affects humans. Clinical signs included emesis, diarrhea, hunched posture consistent with abdominal pain, anemia, and hypoproteinemia. Large gastric masses were present and in one case created a gastric outflow obstruction. Both cases were positive for simian immunodeficiency virus and Helicobacter spp. were variably isolated, although the association with the hypertrophic gastropathy is unclear. Medical treatment had varying success and included sucralfate, H2 receptor antagonists, proton pump inhibitors, diet manipulations, and antibiotic therapies targeting Helicobacter spp. Surgical resection of a large portion of the stomach resulted in some palliative improvement in one case. Overall, this disease presented many challenges regarding identification, confirmation of diagnosis, and clinical management. Both aggressive medical and surgical treatments were unrewarding for long-term management of hypertrophic gastropathy in this pair of red-capped mangabeys and resulted in a poor prognosis in these cases. PMID:24625015

  9. Neuroprotective Effects of Sulforaphane on Cholinergic Neurons in Mice with Alzheimer’s Disease-Like Lesions

    PubMed Central

    Zhang, Rui; Zhang, Jingzhu; Fang, Lingduo; Li, Xi; Zhao, Yue; Shi, Wanying; An, Li

    2014-01-01

    Alzheimer’s disease (AD) is a common neurodegenerative disease in elderly individuals, and effective therapies are unavailable. This study was designed to investigate the neuroprotective effects of sulforaphane (an activator of NF-E2-related factor 2) on mice with AD-like lesions induced by combined administration of aluminum and d-galactose. Step-down-type passive avoidance tests showed sulforaphane ameliorated cognitive impairment in AD-like mice. Immunohistochemistry results indicated sulforaphane attenuated cholinergic neuron loss in the medial septal and hippocampal CA1 regions in AD-like mice. However, spectrophotometry revealed no significant difference in acetylcholine level or the activity of choline acetyltransferase or acetylcholinesterase in the cerebral cortex among groups of control and AD-like mice with and without sulforaphane treatment. Sulforaphane significantly increased the numbers of 5-bromo-2'-deoxyuridine-positive neurons in the subventricular and subgranular zones in AD-like mice which were significantly augmented compared with controls. Atomic absorption spectrometry revealed significantly lower aluminum levels in the brains of sulforaphane-treated AD-like mice than in those that did not receive sulforaphane treatment. In conclusion, sulforaphane ameliorates neurobehavioral deficits by reducing cholinergic neuron loss in the brains of AD-like mice, and the mechanism may be associated with neurogenesis and aluminum load reduction. These findings suggest that phytochemical sulforaphane has potential application in AD therapeutics. PMID:25196440

  10. Doubly Phosphorylated Peptide Vaccines to Protect Transgenic P301S Mice against Alzheimer’s Disease Like Tau Aggregation

    PubMed Central

    Richter, Monique; Mewes, Agneta; Fritsch, Manuela; Krügel, Ute; Hoffmann, Ralf; Singer, David

    2014-01-01

    Intracellular neurofibrillary tangles and extracellular senile plaques are potential targets for active and passive immunotherapies. In this study we used the transgenic mouse model P301S for active immunizations with peptide vaccines composed of a double phosphorylated tau neoepitope (pSer202/pThr205, pThr212/pSer214, pThr231/pSer235) and an immunomodulatory T cell epitope from the tetanus toxin or tuberculosis antigen Ag85B. Importantly, the designed vaccine combining Alzheimer’s disease (AD) specific B cell epitopes with foreign (bacterial) T cell epitopes induced fast immune responses with high IgG1 titers after prophylactic immunization that subsequently decreased over the observation period. The effectiveness of the immunization was surveyed by evaluating the animal behavior, as well as the pathology in the brain by biochemical and histochemical techniques. Immunized mice clearly lived longer with reduced paralysis than placebo-treated mice. Additionally, they performed significantly better in rotarod and beam walk tests at the age of 20 weeks, indicating that the disease development was slowed down. Forty-eight weeks old vaccinated mice passed the beam walk test significantly better than control animals, which together with the increased survival rates undoubtedly prove the treatment effect. In conclusion, the data provide strong evidence that active immune therapies can reduce toxic effects of deposits formed in AD. PMID:26344748

  11. Hydrogen Sulfide Ameliorates Homocysteine-Induced Alzheimer's Disease-Like Pathology, Blood-Brain Barrier Disruption, and Synaptic Disorder.

    PubMed

    Kamat, Pradip K; Kyles, Philip; Kalani, Anuradha; Tyagi, Neetu

    2016-05-01

    Elevated plasma total homocysteine (Hcy) level is associated with an increased risk of Alzheimer's disease (AD). During transsulfuration pathways, Hcy is metabolized into hydrogen sulfide (H2S), which is a synaptic modulator, as well as a neuro-protective agent. However, the role of hydrogen sulfide, as well as N-methyl-D-aspartate receptor (NMDAR) activation, in hyperhomocysteinemia (HHcy) induced blood-brain barrier (BBB) disruption and synaptic dysfunction, leading to AD pathology is not clear. Therefore, we hypothesized that the inhibition of neuronal NMDA-R by H2S and MK801 mitigate the Hcy-induced BBB disruption and synapse dysfunction, in part by decreasing neuronal matrix degradation. Hcy intracerebral (IC) treatment significantly impaired cerebral blood flow (CBF), and cerebral circulation and memory function. Hcy treatment also decreases the expression of cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE) in the brain along with increased expression of NMDA-R (NR1) and synaptosomal Ca(2+) indicating excitotoxicity. Additionally, we found that Hcy treatment increased protein and mRNA expression of intracellular adhesion molecule 1 (ICAM-1), matrix metalloproteinase (MMP)-2, and MMP-9 and also increased MMP-2 and MMP-9 activity in the brain. The increased expression of ICAM-1, glial fibrillary acidic protein (GFAP), and the decreased expression of vascular endothelial (VE)-cadherin and claudin-5 indicates BBB disruption and vascular inflammation. Moreover, we also found decreased expression of microtubule-associated protein 2 (MAP-2), postsynaptic density protein 95 (PSD-95), synapse-associated protein 97 (SAP-97), synaptosomal-associated protein 25 (SNAP-25), synaptophysin, and brain-derived neurotrophic factor (BDNF) showing synapse dysfunction in the hippocampus. Furthermore, NaHS and MK801 treatment ameliorates BBB disruption, CBF, and synapse functions in the mice brain. These results demonstrate a neuro-protective effect of H2S over Hcy

  12. Reducing C-terminal-truncated alpha-synuclein by immunotherapy attenuates neurodegeneration and propagation in Parkinson's disease-like models.

    PubMed

    Games, Dora; Valera, Elvira; Spencer, Brian; Rockenstein, Edward; Mante, Michael; Adame, Anthony; Patrick, Christina; Ubhi, Kiren; Nuber, Silke; Sacayon, Patricia; Zago, Wagner; Seubert, Peter; Barbour, Robin; Schenk, Dale; Masliah, Eliezer

    2014-07-01

    Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are common neurodegenerative disorders of the aging population, characterized by progressive and abnormal accumulation of α-synuclein (α-syn). Recent studies have shown that C-terminus (CT) truncation and propagation of α-syn play a role in the pathogenesis of PD/DLB. Therefore, we explored the effect of passive immunization against the CT of α-syn in the mThy1-α-syn transgenic (tg) mouse model, which resembles the striato-nigral and motor deficits of PD. Mice were immunized with the new monoclonal antibodies 1H7, 5C1, or 5D12, all directed against the CT of α-syn. CT α-syn antibodies attenuated synaptic and axonal pathology, reduced the accumulation of CT-truncated α-syn (CT-α-syn) in axons, rescued the loss of tyrosine hydroxylase fibers in striatum, and improved motor and memory deficits. Among them, 1H7 and 5C1 were most effective at decreasing levels of CT-α-syn and higher-molecular-weight aggregates. Furthermore, in vitro studies showed that preincubation of recombinant α-syn with 1H7 and 5C1 prevented CT cleavage of α-syn. In a cell-based system, CT antibodies reduced cell-to-cell propagation of full-length α-syn, but not of the CT-α-syn that lacked the 118-126 aa recognition site needed for antibody binding. Furthermore, the results obtained after lentiviral expression of α-syn suggest that antibodies might be blocking the extracellular truncation of α-syn by calpain-1. Together, these results demonstrate that antibodies against the CT of α-syn reduce levels of CT-truncated fragments of the protein and its propagation, thus ameliorating PD-like pathology and improving behavioral and motor functions in a mouse model of this disease. PMID:25009275

  13. Reducing C-Terminal-Truncated Alpha-Synuclein by Immunotherapy Attenuates Neurodegeneration and Propagation in Parkinson's Disease-Like Models

    PubMed Central

    Games, Dora; Valera, Elvira; Spencer, Brian; Rockenstein, Edward; Mante, Michael; Adame, Anthony; Patrick, Christina; Ubhi, Kiren; Nuber, Silke; Sacayon, Patricia; Zago, Wagner; Seubert, Peter; Barbour, Robin; Schenk, Dale

    2014-01-01

    Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are common neurodegenerative disorders of the aging population, characterized by progressive and abnormal accumulation of α-synuclein (α-syn). Recent studies have shown that C-terminus (CT) truncation and propagation of α-syn play a role in the pathogenesis of PD/DLB. Therefore, we explored the effect of passive immunization against the CT of α-syn in the mThy1-α-syn transgenic (tg) mouse model, which resembles the striato-nigral and motor deficits of PD. Mice were immunized with the new monoclonal antibodies 1H7, 5C1, or 5D12, all directed against the CT of α-syn. CT α-syn antibodies attenuated synaptic and axonal pathology, reduced the accumulation of CT-truncated α-syn (CT-α-syn) in axons, rescued the loss of tyrosine hydroxylase fibers in striatum, and improved motor and memory deficits. Among them, 1H7 and 5C1 were most effective at decreasing levels of CT-α-syn and higher-molecular-weight aggregates. Furthermore, in vitro studies showed that preincubation of recombinant α-syn with 1H7 and 5C1 prevented CT cleavage of α-syn. In a cell-based system, CT antibodies reduced cell-to-cell propagation of full-length α-syn, but not of the CT-α-syn that lacked the 118–126 aa recognition site needed for antibody binding. Furthermore, the results obtained after lentiviral expression of α-syn suggest that antibodies might be blocking the extracellular truncation of α-syn by calpain-1. Together, these results demonstrate that antibodies against the CT of α-syn reduce levels of CT-truncated fragments of the protein and its propagation, thus ameliorating PD-like pathology and improving behavioral and motor functions in a mouse model of this disease. PMID:25009275

  14. Cotinine halts the advance of Alzheimer's disease-like pathology and associated depressive-like behavior in Tg6799 mice

    PubMed Central

    Patel, Sagar; Grizzell, J. Alex; Holmes, Rosalee; Zeitlin, Ross; Solomon, Rosalynn; Sutton, Thomas L.; Rohani, Adeeb; Charry, Laura C.; Iarkov, Alexandre; Mori, Takashi; Echeverria Moran, Valentina

    2014-01-01

    Alzheimer's disease (AD) is associated with cognitive and non-cognitive symptoms for which there are currently no effective therapies. We have previously reported that cotinine, a natural product obtained from tobacco leaves, prevented memory loss and diminished amyloid-β (Aβ) plaque pathology in transgenic 6799 mice (Tg6799 mice) when treated prior to the development of the pathology. We have also shown that cotinine reduces depressive-like behavior in normal and chronically stressed C57BL/6 mice. Here, we extend our previous studies by investigating the effects of cotinine on the progression of AD-like pathology, depressive-like behavior, and the mechanisms underlying its beneficial effects in Tg6799 mice when left untreated until after a more advanced stage of the disease's development. The results show that vehicle-treated Tg6799 mice displayed an accentuated loss of working memory and an abundant Aβ plaque pathology that were accompanied by higher levels of depressive-like behavior as compared to control littermates. By contrast, prolonged daily cotinine treatment to Tg6799 mice, withheld until after a mid-level progression of AD-like pathology, reduced Aβ levels/plaques and depressive-like behavior. Moreover, this treatment paradigm dramatically improved working memory as compared to control littermates. The beneficial effects of cotinine were accompanied by an increase in the expression of the active form of protein kinase B and the postsynaptic density protein 95 in the hippocampi and frontal cortices of Tg6799 mice. This suggests that cotinine halts the progression of AD-like pathology while reducing depressive-like behavior by stimulating signaling pathways supporting synaptic plasticity in Tg6799 mice. The potential use of cotinine to treat cognitive and non-cognitive symptoms of AD is discussed. PMID:25100990

  15. Histamine Induces Alzheimer's Disease-Like Blood Brain Barrier Breach and Local Cellular Responses in Mouse Brain Organotypic Cultures

    PubMed Central

    Sedeyn, Jonathan C.; Wu, Hao; Hobbs, Reilly D.; Levin, Eli C.; Nagele, Robert G.; Venkataraman, Venkat

    2015-01-01

    Among the top ten causes of death in the United States, Alzheimer's disease (AD) is the only one that cannot be cured, prevented, or even slowed down at present. Significant efforts have been exerted in generating model systems to delineate the mechanism as well as establishing platforms for drug screening. In this study, a promising candidate model utilizing primary mouse brain organotypic (MBO) cultures is reported. For the first time, we have demonstrated that the MBO cultures exhibit increased blood brain barrier (BBB) permeability as shown by IgG leakage into the brain parenchyma, astrocyte activation as evidenced by increased expression of glial fibrillary acidic protein (GFAP), and neuronal damage-response as suggested by increased vimentin-positive neurons occur upon histamine treatment. Identical responses—a breakdown of the BBB, astrocyte activation, and neuronal expression of vimentin—were then demonstrated in brains from AD patients compared to age-matched controls, consistent with other reports. Thus, the histamine-treated MBO culture system may provide a valuable tool in combating AD. PMID:26697497

  16. A Review of Bacteria-Animal Lateral Gene Transfer May Inform Our Understanding of Diseases like Cancer

    PubMed Central

    Robinson, Kelly M.; Sieber, Karsten B.; Dunning Hotopp, Julie C.

    2013-01-01

    Lateral gene transfer (LGT) from bacteria to animals occurs more frequently than was appreciated prior to the advent of genome sequencing. In 2007, LGT from bacterial Wolbachia endosymbionts was detected in ∼33% of the sequenced arthropod genomes using a bioinformatic approach. Today, Wolbachia/host LGT is thought to be widespread and many other cases of bacteria-animal LGT have been described. In insects, LGT may be more frequently associated with endosymbionts that colonize germ cells and germ stem cells, like Wolbachia endosymbionts. We speculate that LGT may occur from bacteria to a wide variety of eukaryotes, but only becomes vertically inherited when it occurs in germ cells. As such, LGT may happen routinely in somatic cells but never become inherited or fixed in the population. Lack of inheritance of such mutations greatly decreases our ability to detect them. In this review, we propose that such noninherited bacterial DNA integration into chromosomes in human somatic cells could induce mutations leading to cancer or autoimmune diseases in a manner analogous to mobile elements and viral integrations. PMID:24146634

  17. Histamine Induces Alzheimer's Disease-Like Blood Brain Barrier Breach and Local Cellular Responses in Mouse Brain Organotypic Cultures.

    PubMed

    Sedeyn, Jonathan C; Wu, Hao; Hobbs, Reilly D; Levin, Eli C; Nagele, Robert G; Venkataraman, Venkat

    2015-01-01

    Among the top ten causes of death in the United States, Alzheimer's disease (AD) is the only one that cannot be cured, prevented, or even slowed down at present. Significant efforts have been exerted in generating model systems to delineate the mechanism as well as establishing platforms for drug screening. In this study, a promising candidate model utilizing primary mouse brain organotypic (MBO) cultures is reported. For the first time, we have demonstrated that the MBO cultures exhibit increased blood brain barrier (BBB) permeability as shown by IgG leakage into the brain parenchyma, astrocyte activation as evidenced by increased expression of glial fibrillary acidic protein (GFAP), and neuronal damage-response as suggested by increased vimentin-positive neurons occur upon histamine treatment. Identical responses-a breakdown of the BBB, astrocyte activation, and neuronal expression of vimentin-were then demonstrated in brains from AD patients compared to age-matched controls, consistent with other reports. Thus, the histamine-treated MBO culture system may provide a valuable tool in combating AD. PMID:26697497

  18. N-butylidenephthalide attenuates Alzheimer's disease-like cytopathy in Down syndrome induced pluripotent stem cell-derived neurons.

    PubMed

    Chang, Chia-Yu; Chen, Sheng-Mei; Lu, Huai-En; Lai, Syu-Ming; Lai, Ping-Shan; Shen, Po-Wen; Chen, Pei-Ying; Shen, Ching-I; Harn, Horng-Jyh; Lin, Shinn-Zong; Hwang, Shiaw-Min; Su, Hong-Lin

    2015-01-01

    Down syndrome (DS) patients with early-onset dementia share similar neurodegenerative features with Alzheimer's disease (AD). To recapitulate the AD cell model, DS induced pluripotent stem cells (DS-iPSCs), reprogrammed from mesenchymal stem cells in amniotic fluid, were directed toward a neuronal lineage. Neuroepithelial precursor cells with high purity and forebrain characteristics were robustly generated on day 10 (D10) of differentiation. Accumulated amyloid deposits, Tau protein hyperphosphorylation and Tau intracellular redistribution emerged rapidly in DS neurons within 45 days but not in normal embryonic stem cell-derived neurons. N-butylidenephthalide (Bdph), a major phthalide ingredient of Angelica sinensis, was emulsified by pluronic F127 to reduce its cellular toxicity and promote canonical Wnt signaling. Interestingly, we found that F127-Bdph showed significant therapeutic effects in reducing secreted Aβ40 deposits, the total Tau level and the hyperphosphorylated status of Tau in DS neurons. Taken together, DS-iPSC derived neural cells can serve as an ideal cellular model of DS and AD and have potential for high-throughput screening of candidate drugs. We also suggest that Bdph may benefit DS or AD treatment by scavenging Aβ aggregates and neurofibrillary tangles. PMID:25735452

  19. Neural stem cell transplantation enhances mitochondrial biogenesis in a transgenic mouse model of Alzheimer's disease-like pathology.

    PubMed

    Zhang, Wei; Gu, Guo-Jun; Shen, Xing; Zhang, Qi; Wang, Gang-Min; Wang, Pei-Jun

    2015-03-01

    Mitochondrial dysfunction, especially a defect in mitochondrial biogenesis, is an early and prominent feature of Alzheimer's disease (AD). Previous studies demonstrated that the number of mitochondria is significantly reduced in susceptible hippocampal neurons from AD patients. Neural stem cell (NSC) transplantation in AD-like mice can compensate for the neuronal loss resulting from amyloid-beta protein deposition. The effects of NSC transplantation on mitochondrial biogenesis and cognitive function in AD-like mice, however, are poorly understood. In this study, we injected NSCs or vehicle into 12-month-old amyloid precursor protein (APP)/PS1 transgenic mice, a mouse model of AD-like pathology. The effects of NSC transplantation on cognitive function, the amount of mitochondrial DNA, the expression of mitochondrial biogenesis factors and mitochondria-related proteins, and mitochondrial morphology were investigated. Our results show that in NSC-injected APP/PS1 (Tg-NSC) mice, the cognitive function, number of mitochondria, and expression of mitochondria-related proteins, specifically the mitochondrial fission factors (dynamin-related protein 1 [Drp1] and fission 1 [Fis1]) and the mitochondrial fusion factor optic atrophy 1 (OPA1), were significantly increased compared with those in age-matched vehicle-injected APP/PS1 (Tg-Veh) mice, whereas the expression of mitochondrial fusion factors mitofusion 1 (Mfn1) and Mfn2 was significantly decreased. These data indicate that NSC transplantation may enhance mitochondria biogenesis and further rescue cognitive deficits in AD-like mice. PMID:25582749

  20. N-butylidenephthalide Attenuates Alzheimer's Disease-Like Cytopathy in Down Syndrome Induced Pluripotent Stem Cell-Derived Neurons

    PubMed Central

    Chang, Chia-Yu; Chen, Sheng-Mei; Lu, Huai-En; Lai, Syu-Ming; Lai, Ping-Shan; Shen, Po-Wen; Chen, Pei-Ying; Shen, Ching-I; Harn, Horng-Jyh; Lin, Shinn-Zong; Hwang, Shiaw-Min; Su, Hong-Lin

    2015-01-01

    Down syndrome (DS) patients with early-onset dementia share similar neurodegenerative features with Alzheimer's disease (AD). To recapitulate the AD cell model, DS induced pluripotent stem cells (DS-iPSCs), reprogrammed from mesenchymal stem cells in amniotic fluid, were directed toward a neuronal lineage. Neuroepithelial precursor cells with high purity and forebrain characteristics were robustly generated on day 10 (D10) of differentiation. Accumulated amyloid deposits, Tau protein hyperphosphorylation and Tau intracellular redistribution emerged rapidly in DS neurons within 45 days but not in normal embryonic stem cell-derived neurons. N-butylidenephthalide (Bdph), a major phthalide ingredient of Angelica sinensis, was emulsified by pluronic F127 to reduce its cellular toxicity and promote canonical Wnt signaling. Interestingly, we found that F127-Bdph showed significant therapeutic effects in reducing secreted Aβ40 deposits, the total Tau level and the hyperphosphorylated status of Tau in DS neurons. Taken together, DS-iPSC derived neural cells can serve as an ideal cellular model of DS and AD and have potential for high-throughput screening of candidate drugs. We also suggest that Bdph may benefit DS or AD treatment by scavenging Aβ aggregates and neurofibrillary tangles. PMID:25735452

  1. Is the efficacy of biological control against plant diseases likely to be more durable than that of chemical pesticides?

    PubMed Central

    Bardin, Marc; Ajouz, Sakhr; Comby, Morgane; Lopez-Ferber, Miguel; Graillot, Benoît; Siegwart, Myriam; Nicot, Philippe C.

    2015-01-01

    The durability of a control method for plant protection is defined as the persistence of its efficacy in space and time. It depends on (i) the selection pressure exerted by it on populations of plant pathogens and (ii) on the capacity of these pathogens to adapt to the control method. Erosion of effectiveness of conventional plant protection methods has been widely studied in the past. For example, apparition of resistance to chemical pesticides in plant pathogens or pests has been extensively documented. The durability of biological control has often been assumed to be higher than that of chemical control. Results concerning pest management in agricultural systems have shown that this assumption may not always be justified. Resistance of various pests to one or several toxins of Bacillus thuringiensis and apparition of resistance of the codling moth Cydia pomonella to the C. pomonella granulovirus have, for example, been described. In contrast with the situation for pests, the durability of biological control of plant diseases has hardly been studied and no scientific reports proving the loss of efficiency of biological control agents against plant pathogens in practice has been published so far. Knowledge concerning the possible erosion of effectiveness of biological control is essential to ensure a durable efficacy of biological control agents on target plant pathogens. This knowledge will result in identifying risk factors that can foster the selection of strains of plant pathogens resistant to biological control agents. It will also result in identifying types of biological control agents with lower risk of efficacy loss, i.e., modes of action of biological control agents that does not favor the selection of resistant isolates in natural populations of plant pathogens. An analysis of the scientific literature was then conducted to assess the potential for plant pathogens to become resistant to biological control agents. PMID:26284088

  2. “A Disease Like Any Other”? A Decade of Change in Public Reactions to Schizophrenia, Depression, and Alcohol Dependence

    PubMed Central

    Pescosolido, Bernice A.; Martin, Jack K.; Long, J. Scott; Medina, Tait R.; Phelan, Jo C.; Link, Bruce G.

    2015-01-01

    Objective Clinicians, advocates, and policy makers have presented mental illnesses as medical diseases in efforts to overcome low service use, poor adherence rates, and stigma. The authors examined the impact of this approach with a 10-year comparison of public endorsement of treatment and prejudice. Method The authors analyzed responses to vignettes in the mental health modules of the 1996 and 2006 General Social Survey describing individuals meeting DSM-IV criteria for schizophrenia, major depression, and alcohol dependence to explore whether more of the public 1) embraces neurobiological understandings of mental illness; 2) endorses treatment from providers, including psychiatrists; and 3) reports community acceptance or rejection of people with these disorders. Multivariate analyses examined whether acceptance of neurobiological causes increased treatment support and lessened stigma. Results In 2006, 67% of the public attributed major depression to neurobiological causes, compared with 54% in 1996. High proportions of respondents endorsed treatment, with general increases in the proportion endorsing treatment from doctors and specific increases in the proportions endorsing psychiatrists for treatment of alcohol dependence (from 61% in 1996 to 79% in 2006) and major depression (from 75% in 1996 to 85% in 2006). Social distance and perceived danger associated with people with these disorders did not decrease significantly. Holding a neurobiological conception of these disorders increased the likelihood of support for treatment but was generally unrelated to stigma. Where associated, the effect was to increase, not decrease, community rejection. Conclusions More of the public embraces a neurobiological understanding of mental illness. This view translates into support for services but not into a decrease in stigma. Reconfiguring stigma reduction strategies may require providers and advocates to shift to an emphasis on competence and inclusion. PMID:20843872

  3. Altered expression of Mg(2+) transport proteins during Parkinson's disease-like dopaminergic cell degeneration in PC12 cells.

    PubMed

    Shindo, Yutaka; Yamanaka, Ryu; Suzuki, Koji; Hotta, Kohji; Oka, Kotaro

    2016-08-01

    Mg(2+) is an essential cation to maintain cellular functions, and intracellular Mg(2+) concentration ([Mg(2+)]i) is regulated by Mg(2+) channels and transporters. In our previous study, we demonstrated that MPP(+) elicits Mg(2+) influx across the cell membrane and Mg(2+) mobilization from mitochondria, and the resulting [Mg(2+)]i is an important determinants of the cell viability in MPP(+) model of Parkinson's disease (PD). It indicates that cellular Mg(2+) transport is one of the important factors to determine the progress of PD. However, whether the expression levels of Mg(2+) transport proteins change in the progress of PD has still been obscure. In this study, we estimated the mRNA expression levels of Mg(2+) transport proteins upon the exposure to MPP(+). In thirteen Mg(2+) transport proteins examined, mRNA expression level of SLC41A2 was increased and that of ACDP2, NIPA1 and MMgT2 were decreased. Knockdown of SLC41A2, ACDP2 or NIPA1 accelerated the MPP(+)-induced cell degeneration, and overexpression attenuated it. The decrease in the mRNA expression levels of NIPA1 and MMgT2 were also elicited by rotenone, H2O2 and FCCP, indicating that mitochondrial dysfunction related to this down-regulation. The increase in that of SLC41A2 was induced by an uncoupler, FCCP, as well as MPP(+), suggesting that it is an intrinsic protection mechanism against depolarized mitochondrial membrane potential and/or cellular ATP depletion. Our results shown here indicate that alteration of Mg(2+) transport proteins is implicated in the MPP(+) model of PD, and it affects cell degeneration. PMID:27157538

  4. Transgenic mice expressing the p75 CCAAT-displacement protein/Cut homeobox isoform develop a myeloproliferative disease-like myeloid leukemia.

    PubMed

    Cadieux, Chantal; Fournier, Sylvie; Peterson, Alan C; Bédard, Christian; Bedell, Barry J; Nepveu, Alain

    2006-10-01

    The p75 CCAAT-displacement protein/Cut homeobox (CDP/Cux) isoform was previously reported to be overexpressed in human breast cancers. To investigate its oncogenic potential, we engineered two transgenic mouse lines expressing p75 CDP/Cux under the control of the mouse mammary tumor virus-long terminal repeat. The FVB strain of mouse is generally used in the generation of mouse models for breast cancer. The transgene was introduced into the hprt locus of 129/Ola embryonic stem cells and, following germ line passage, was backcrossed onto the FVB and C57BL/6 mouse strains. Here, we describe the phenotype of p75 CDP/Cux transgenic virgin female mice of the first backcross generations. We report that after a long latency period, approximately 33% of mice from two independent transgenic lines and from backcrosses into either the FVB or the C57BL/6 strains succumbed to a similar disease characterized by splenomegaly, hepatomegaly, and frequent infiltration of leukocytes into nonhematopoietic organs like the kidneys and lungs. Although an excess of B or T cells was observed in three diseased mice, in 17 other cases, histologic and flow cytometry analyses revealed the expansion of a population of neutrophils in the blood, spleen, and bone marrow. The increase in neutrophils correlated with signs of anemia and thrombocytopenia, whereas there was no indication of a reactive process. Therefore, p75 CDP/Cux transgenic mice displayed heightened susceptibility to a disease defined as a myeloproliferative disease-like myeloid leukemia. These results indicate that the overexpression of p75 CDP/Cux could alter homeostasis in the hematopoietic compartment. PMID:17018605

  5. Neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) slows down Alzheimer's disease-like pathology in amyloid precursor protein-transgenic mice

    PubMed Central

    Rat, Dorothea; Schmitt, Ulrich; Tippmann, Frank; Dewachter, Ilse; Theunis, Clara; Wieczerzak, Ewa; Postina, Rolf; van Leuven, Fred; Fahrenholz, Falk; Kojro, Elzbieta

    2011-01-01

    Pituitary adenylate cyclase-activating polypeptide (PACAP) has neuroprotective and neurotrophic properties and is a potent α-secretase activator. As PACAP peptides and their specific receptor PAC1 are localized in central nervous system areas affected by Alzheimer's disease (AD), this study aims to examine the role of the natural peptide PACAP as a valuable approach in AD therapy. We investigated the effect of PACAP in the brain of an AD transgenic mouse model. The long-term intranasal daily PACAP application stimulated the nonamyloidogenic processing of amyloid precursor protein (APP) and increased expression of the brain-derived neurotrophic factor and of the antiapoptotic Bcl-2 protein. In addition, it caused a strong reduction of the amyloid β-peptide (Aβ) transporter receptor for advanced glycation end products (RAGE) mRNA level. PACAP, by activation of the somatostatin-neprilysin cascade, also enhanced expression of the Aβ-degrading enzyme neprilysin in the mouse brain. Furthermore, daily PAC1-receptor activation via PACAP resulted in an increased mRNA level of both the PAC1 receptor and its ligand PACAP. Our behavioral studies showed that long-term PACAP treatment of APP[V717I]-transgenic mice improved cognitive function in animals. Thus, nasal application of PACAP was effective, and our results indicate that PACAP could be of therapeutic value in treating AD.—Rat, D., Schmitt, U., Tippmann, F., Dewachter, I., Theunis, C., Wieczerzak, E, Postina, R., van Leuven, F., Fahrenholz, F., Kojro, E. Neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) slows down Alzheimer's disease-like pathology in amyloid precursor protein-transgenic mice. PMID:21593432

  6. Understanding and living with glaucoma and non-communicable diseases like hypertension and diabetes in the Jhaukhel-Duwakot Health Demographic Surveillance Site: a qualitative study from Nepal

    PubMed Central

    Shakya-Vaidya, Suraj; Povlsen, Lene; Shrestha, Binjwala; Grjibovski, Andrej M.; Krettek, Alexandra

    2014-01-01

    Background Primary open-angle glaucoma (POAG) is one of the most common causes of irreversible blindness. A possible association between POAG and non-communicable diseases such as hypertension and diabetes suggests that the incidence of POAG may increase. People with POAG in Nepal usually present late to hospital and have poor knowledge of glaucoma. Objectives Anticipating a knowledge gap regarding these diseases, this study aimed to explore the knowledge of POAG, hypertension, and diabetes in the community and barriers to health care. Design We conducted this qualitative study in the Jhaukhel-Duwakot Health Demographic Surveillance Site (JD-HDSS), a peri-urban community near Kathmandu, a capital city of Nepal. To study how disease influences knowledge, we conducted focus group discussions separately for men and women with and without pre-existing POAG, hypertension, and diabetes. Data were analyzed using the framework analysis approach. Results Although people suffering from POAG, hypertension, and/or diabetes exhibited adequate knowledge of hypertension and diabetes, they lacked in-depth knowledge of POAG. People believed mostly in internal health locus of control. Perception of disease consequences and impact of disease on daily life was influenced by pre-existing POAG, hypertension, and/or diabetes but only in men. Gender disparity was observed regarding health literacy, health perception, and health barriers, which put women in a more difficult situation to tackle their health. We also revealed a gap between knowledge, attitude, and practice of health among women and healthy men. Conclusion Although people in JD-HDSS exhibited adequate knowledge regarding hypertension and diabetes, they lacked in-depth knowledge about POAG. This study demonstrated gender difference in health literacy and access to health care, making women more vulnerable towards disease. We also demonstrated a gap between knowledge, attitude, and practice of health. However, tailored health

  7. Concomitant Presentation of Hemophagocytic Lymphohistiocytosis and Posttransplant Lymphoproliferative Disease-Like Lymphoma in a Mildly Immunosuppressed Leukemia Patient: An Unusual Association.

    PubMed

    Sinno, Mohamad G; Rosen, David; Wittler, Robert

    2016-08-01

    We describe a 4-year-old female with pre-B-cell acute lymphoblastic leukemia on maintenance chemotherapy, who developed hemophagocytic lymphohistiocytosis (HLH) secondary to Epstein-Barr virus (EBV) infection, complicated by an aggressive lymphoproliferative disorder. Although there was no history of bone marrow transplant or underlying immunodeficiency, EBV triggered a post-transplant lymphoproliferative disease (PTLD)-like lymphoma. Multiple regimens of chemotherapy failed to induce remission and patient developed multiorgan failure. The association of HLH with EBV-related PTLD-like lymphoproliferative disorder is rare. We present this case to highlight this unusual association so that this highly fatal disease can be recognized and promptly addressed. PMID:27148941

  8. Gene Expression Studies on Human Trisomy 21 iPSCs and Neurons: Towards Mechanisms Underlying Down's Syndrome and Early Alzheimer's Disease-Like Pathologies.

    PubMed

    Weick, Jason P; Kang, Huining; Bonadurer, George F; Bhattacharyya, Anita

    2016-01-01

    The cause of Alzheimer disease (AD) is not well understood and there is no cure. Our ability to understand the early events in the course of AD is severely limited by the difficulty of identifying individuals who are in the early, preclinical stage of this disease. Most individuals with Down's syndrome (DS, trisomy 21) will predictably develop AD and that they will do so at a young age makes them an ideal population in which to study the early stages of AD. Several recent studies have exploited induced pluripotent stem cells (iPSCs) generated from individuals with familial AD, spontaneous AD and DS to attempt to identify early events and discover novel biomarkers of disease progression in AD. Here, we summarize the progress and limitations of these iPSC studies with a focus on iPSC-derived neurons. Further, we outline the methodology and results for comparing gene expression between AD and DS iPSC-derived neurons. We highlight differences and commonalities in these data that may implicate underlying genes and pathways that are causative for AD. PMID:26235072

  9. 6-hydroxydopamine-induced Parkinson's disease-like degeneration generates acute microgliosis and astrogliosis in the nigrostriatal system but no bioluminescence imaging-detectable alteration in adult neurogenesis.

    PubMed

    Fricke, Inga B; Viel, Thomas; Worlitzer, Maik M; Collmann, Franziska M; Vrachimis, Alexis; Faust, Andreas; Wachsmuth, Lydia; Faber, Cornelius; Dollé, Frédéric; Kuhlmann, Michael T; Schäfers, Klaus; Hermann, Sven; Schwamborn, Jens C; Jacobs, Andreas H

    2016-05-01

    Parkinson's disease is a slowly progressing neurodegenerative disorder caused by loss of dopaminergic neurons in the substantia nigra (SN), leading to severe impairment in motor and non-motor functions. Endogenous subventricular zone (SVZ) neural stem cells constantly give birth to new cells that might serve as a possible source for regeneration in the adult brain. However, neurodegeneration is accompanied by neuroinflammation and dopamine depletion, potentially compromising regeneration. We therefore employed in vivo imaging methods to study striatal deafferentation (N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-[(123) I]iodophenyl)nortropane single photon emission computed tomography, DaTscan(™) ) and neuroinflammation in the SN and striatum (N,N-diethyl-2-(2-(4-(2-[(18) F]fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide positron emission tomography, [(18) F]DPA-714 PET) in the intranigral 6-hydroxydopamine Parkinson's disease mouse model. Additionally, we transduced cells in the SVZ with a lentivirus encoding firefly luciferase and followed migration of progenitor cells in the SVZ-olfactory bulb axis via bioluminescence imaging under disease and control conditions. We found that activation of microglia in the SN is an acute process accompanying the degeneration of dopaminergic cell bodies in the SN. Dopaminergic deafferentation of the striatum does not influence the generation of doublecortin-positive neuroblasts in the SVZ, but generates chronic astrogliosis in the nigrostriatal system. PMID:26950181

  10. A novel therapeutic application of solid lipid nanoparticles encapsulated thymoquinone (TQ-SLNs) on 3-nitroproponic acid induced Huntington's disease-like symptoms in wistar rats.

    PubMed

    Ramachandran, Surekha; Thangarajan, Sumathi

    2016-08-25

    Huntington's disease (HD), a devastating neurodegenerative disease causing a remarkable pathogenesis involves mitochondrial dysfunction and bioenergetics failure. 3-Nitropropionic acid (3-NP) is a unique toxin model of HD that are mainly confined to mitochondrial complex-II inhibition and free radical generation. Recently, several nanoparticle formulations were developed to treat against various neurodegenerative diseases including HD. One among them is solid lipid nanoparticles (SLNs), a colloidal carrier designed to enhance the brain drug delivery and to prolong the bio-availability of drugs in the system. Hence, the present study was framed to evaluate solid lipid nanoparticles encapsulated thymoquinone (TQ-SLNs) in comparison with thymoquinone suspension (TQ-S) against 3-NP induced behavioral despair, oxidative injury and striatal pathology. This study reports that theTQ-SLNs (10 and 20 mg/kg) and TQ-S (80 mg/kg) treated animals showed a significant (P < 0.01) improvement in the muscle strength, rigidity, movement and memory performances on 7th and 14th day behavioral analysis than TQ-S (40 mg/kg) treated group. Similarly, TQ-SLNs highly attenuated the levels of oxidative stress markers such as LPO, NO and protein carbonylsin 3-NP induced animals. Further, TQ-SLNs significantly restored the antioxidant defense system, controls the mitochondrial SDH inhibition and alleviates anti-cholinergic effect upon 3-NP induction. In addition, TQ-SLNs efficiently protected the striatal structural microelements against 3-NP toxicity, which was confirmed by light microscopic studies. Thus, the present investigation, collectively suggests that the low dose of TQ-SLNs supplementation is highly sufficient to attain the effect of TQ-S (80 mg/kg) to attenuate behavioral, biochemical and histological modifications in 3-NP exposed HD model. PMID:27206696

  11. Alzheimer’s Disease-Like Tau Neuropathology Leads to Memory Deficits and Loss of Functional Synapses in a Novel Mutated Tau Transgenic Mouse without Any Motor Deficits

    PubMed Central

    Schindowski, Katharina; Bretteville, Alexis; Leroy, Karelle; Bégard, Séverine; Brion, Jean-Pierre; Hamdane, Malika; Buée, Luc

    2006-01-01

    Tau transgenic mice are valuable models to investigate the role of tau protein in Alzheimer’s disease and other tauopathies. However, motor dysfunction and dystonic posture interfering with behavioral testing are the most common undesirable effects of tau transgenic mice. Therefore, we have generated a novel mouse model (THY-Tau22) that expresses human 4-repeat tau mutated at sites G272V and P301S under a Thy1.2-promotor, displaying tau pathology in the absence of any motor dysfunction. THY-Tau22 shows hyperphosphorylation of tau on several Alzheimer’s disease-relevant tau epitopes (AT8, AT100, AT180, AT270, 12E8, tau-pSer396, and AP422), neurofibrillary tangle-like inclusions (Gallyas and MC1-positive) with rare ghost tangles and PHF-like filaments, as well as mild astrogliosis. These mice also display deficits in hippocampal synaptic transmission and impaired behavior characterized by increased anxiety, delayed learning from 3 months, and reduced spatial memory at 10 months. There are no signs of motor deficits or changes in motor activity at any age investigated. This mouse model therefore displays the main features of tau pathology and several of the pathophysiological disturbances observed during neurofibrillary degeneration. This model will serve as an experimental tool in future studies to investigate mechanisms underlying cognitive deficits during pathogenic tau aggregation. PMID:16877359

  12. NO2 inhalation promotes Alzheimer’s disease-like progression: cyclooxygenase-2-derived prostaglandin E2 modulation and monoacylglycerol lipase inhibition-targeted medication

    NASA Astrophysics Data System (ADS)

    Yan, Wei; Yun, Yang; Ku, Tingting; Li, Guangke; Sang, Nan

    2016-03-01

    Air pollution has been reported to be associated with increased risks of cognitive impairment and neurodegenerative diseases. Because NO2 is a typical primary air pollutant and an important contributor to secondary aerosols, NO2-induced neuronal functional abnormalities have attracted greater attention, but the available experimental evidence, modulating mechanisms, and targeting medications remain ambiguous. In this study, we exposed C57BL/6J and APP/PS1 mice to dynamic NO2 inhalation and found for the first time that NO2 inhalation caused deterioration of spatial learning and memory, aggravated amyloid β42 (Aβ42) accumulation, and promoted pathological abnormalities and cognitive defects related to Alzheimer’s disease (AD). The microarray and bioinformation data showed that the cyclooxygenase-2 (COX-2)-mediated arachidonic acid (AA) metabolism of prostaglandin E2 (PGE2) played a key role in modulating this aggravation. Furthermore, increasing endocannabinoid 2-arachidonoylglycerol (2-AG) by inhibiting monoacylglycerol lipase (MAGL) prevented PGE2 production, neuroinflammation-associated Aβ42 accumulation, and neurodegeneration, indicating a therapeutic target for relieving cognitive impairment caused by NO2 exposure.

  13. NO2 inhalation promotes Alzheimer’s disease-like progression: cyclooxygenase-2-derived prostaglandin E2 modulation and monoacylglycerol lipase inhibition-targeted medication

    PubMed Central

    Yan, Wei; Yun, Yang; Ku, Tingting; Li, Guangke; Sang, Nan

    2016-01-01

    Air pollution has been reported to be associated with increased risks of cognitive impairment and neurodegenerative diseases. Because NO2 is a typical primary air pollutant and an important contributor to secondary aerosols, NO2-induced neuronal functional abnormalities have attracted greater attention, but the available experimental evidence, modulating mechanisms, and targeting medications remain ambiguous. In this study, we exposed C57BL/6J and APP/PS1 mice to dynamic NO2 inhalation and found for the first time that NO2 inhalation caused deterioration of spatial learning and memory, aggravated amyloid β42 (Aβ42) accumulation, and promoted pathological abnormalities and cognitive defects related to Alzheimer’s disease (AD). The microarray and bioinformation data showed that the cyclooxygenase-2 (COX-2)-mediated arachidonic acid (AA) metabolism of prostaglandin E2 (PGE2) played a key role in modulating this aggravation. Furthermore, increasing endocannabinoid 2-arachidonoylglycerol (2-AG) by inhibiting monoacylglycerol lipase (MAGL) prevented PGE2 production, neuroinflammation-associated Aβ42 accumulation, and neurodegeneration, indicating a therapeutic target for relieving cognitive impairment caused by NO2 exposure. PMID:26928013

  14. Behçet’s disease-like syndrome secondary to microbial infection: a case report and review of the literature

    PubMed Central

    Zhang, Lingshu; Xu, Yuan; Peng, Yun; Yan, Bing; Liu, Yi

    2015-01-01

    Behçet’s disease (BD)-like syndrome is an extremely rare situation occurred after Mycobacterium tuberculosis infection and virus infection. We reported a 45-year-old woman who visited our hospital complaining of swollen left ankle, painful genital ulcer, redness in the left eye and skin rash on lower limbs. The patient had a history of pleural tuberculosis and had received anti-tuberculous therapy for one year. Her left cervical lymph node sample demonstrated tubercle bacilli DNA fragmentation. The diagnosis of tuberculous lymphadenitis and Behçet’s disease (BD)-like syndrome were made. This patient’s symptoms remitted following treatment with anti-tuberculous therapy. This case indicates that some microbial infection can trigger the onset of BD-like syndrome in genetically susceptible subjects. However, treatment strategy of BD-like syndrome secondary to infection is totally different from primary BD. The aim of this case report is to present our experience of the different clinical signs and treatment of BD-like syndrome to expedite its early diagnosis in future. Combination of clinical, radiological, immunophenotypic, pathological, and genetic data contribute to improving the rate of diagnosis. PMID:26722585

  15. Normal Molecular Specification and Neurodegenerative Disease-Like Death of Spinal Neurons Lacking the SNARE-Associated Synaptic Protein Munc18-1

    PubMed Central

    Law, Chris; Schaan Profes, Marcos; Levesque, Martin; Kaltschmidt, Julia A.; Verhage, Matthijs

    2016-01-01

    The role of synaptic activity during early formation of neural circuits is a topic of some debate; genetic ablation of neurotransmitter release by deletion of the Munc18-1 gene provides an excellent model to answer the question of whether such activity is required for early circuit formation. Previous analysis of Munc18-1−/− mouse mutants documented their grossly normal nervous system, but its molecular differentiation has not been assessed. Munc18-1 deletion in mice also results in widespread neurodegeneration that remains poorly characterized. In this study, we demonstrate that the early stages of spinal motor circuit formation, including motor neuron specification, axon growth and pathfinding, and mRNA expression, are unaffected in Munc18-1−/− mice, demonstrating that synaptic activity is dispensable for early nervous system development. Furthermore, we show that the neurodegeneration caused by Munc18-1 loss is cell autonomous, consistent with apparently normal expression of several neurotrophic factors and normal GDNF signaling. Consistent with cell-autonomous degeneration, we demonstrate defects in the trafficking of the synaptic proteins Syntaxin1a and PSD-95 and the TrkB and DCC receptors in Munc18-1−/− neurons; these defects do not appear to cause ER stress, suggesting other mechanisms for degeneration. Finally, we demonstrate pathological similarities to Alzheimer's disease, such as altered Tau phosphorylation, neurofibrillary tangles, and accumulation of insoluble protein plaques. Together, our results shed new light upon the neurodegeneration observed in Munc18-1−/− mice and argue that this phenomenon shares parallels with neurodegenerative diseases. SIGNIFICANCE STATEMENT In this work, we demonstrate the absence of a requirement for regulated neurotransmitter release in the assembly of early neuronal circuits by assaying transcriptional identity, axon growth and guidance, and mRNA expression in Munc18-1-null mice. Furthermore, we

  16. T-cell brain infiltration and immature antigen-presenting cells in transgenic models of Alzheimer's disease-like cerebral amyloidosis.

    PubMed

    Ferretti, M T; Merlini, M; Späni, C; Gericke, C; Schweizer, N; Enzmann, G; Engelhardt, B; Kulic, L; Suter, T; Nitsch, R M

    2016-05-01

    Cerebral beta-amyloidosis, one of the pathological hallmarks of Alzheimer's disease (AD), elicits a well-characterised, microglia-mediated local innate immune response. In contrast, it is not clear whether cells of the adaptive immune system, in particular T-cells, react to cerebral amyloidosis in AD. Even though parenchymal T-cells have been described in post-mortem brains of AD patients, it is not known whether infiltrating T-cells are specifically recruited to the extracellular deposits of beta-amyloid, and whether they are locally activated into proliferating, effector cells upon interaction with antigen-presenting cells (APCs). To address these issues we have analysed by confocal microscopy and flow-cytometry the localisation and activation status of both T-cells and APCs in transgenic (tg) mice models of AD-like cerebral amyloidosis. Increased numbers of infiltrating T-cells were found in amyloid-burdened brain regions of tg mice, with concomitant up-regulation of endothelial adhesion molecules ICAM-1 and VCAM-1, compared to non-tg littermates. The infiltrating T-cells in tg brains did not co-localise with amyloid plaques, produced less interferon-gamma than those in controls and did not proliferate locally. Bona-fide dendritic cells were virtually absent from the brain parenchyma of both non-tg and tg mice, and APCs from tg brains showed an immature phenotype, with accumulation of MHC-II in intracellular compartments. These results indicate that cerebral amyloidosis promotes T-cell infiltration but interferes with local antigen presentation and T-cell activation. The inability of the brain immune surveillance to orchestrate a protective immune response to amyloid-beta peptide might contribute to the accumulation of amyloid in the progression of the disease. PMID:26872418

  17. Intramuscular delivery of p75NTR ectodomain by an AAV vector attenuates cognitive deficits and Alzheimer's disease-like pathologies in APP/PS1 transgenic mice.

    PubMed

    Wang, Qing-Hua; Wang, Ye-Ran; Zhang, Tao; Jiao, Shu-Sheng; Liu, Yu-Hui; Zeng, Fan; Li, Jing; Yao, Xiu-Qing; Zhou, Hua-Dong; Zhou, Xin-Fu; Wang, Yan-Jiang

    2016-07-01

    The neurotrophin receptor p75 (p75NTR) is a receptor for amyloid-beta (Aβ) and mediates Aβ-induced neurodegenerative signals. The ectodomain of p75NTR (p75ECD) is a physiological protective factor against Aβ in Alzheimer's disease (AD). We have previously demonstrated that the shedding of p75ECD from the cell surface is down-regulated in AD brains and restoration of the p75ECD level in the brain, through intracranial administration of p75ECD by adeno-associated virus vectors, attenuates AD-like pathologies in an AD mouse model. In this study, we further investigated the feasibility and efficacy of peripheral administration of AAV-p75ECD on brain amyloid burden and associated pathogenesis. We found that intramuscular delivery of AAV-p75ECD increased the level of p75ECD in the blood, significantly improved the behavioral phenotype of amyloid precursor protein/PS1 transgenic mice, and reduced brain amyloid burden, attenuated Tau hyperphosphorylation, and neuroinflammation. Furthermore, intramuscular delivery of AAV-p75ECD was well tolerated. Our results indicate that peripheral delivery of p75ECD represents a safe and effective therapeutic strategy for AD. The ectodomain of p75NTR (p75ECD) is a physiological protective factor against amyloid-beta (Aβ) in Alzheimer's disease (AD). Intramuscular delivery of AAV-p75ECD increased the p75ECD levels in the blood, reduced brain amyloid burden through a 'peripheral sink' mechanism and alleviates AD-type pathologies. Peripheral delivery of p75ECD represents a promising therapeutic strategy for AD. PMID:26991827

  18. Cholesterol lowering effects of mono-lactose-appended β-cyclodextrin in Niemann–Pick type C disease-like HepG2 cells

    PubMed Central

    Motoyama, Keiichi; Hirai, Yumi; Nishiyama, Rena; Maeda, Yuki; Higashi, Taishi; Ishitsuka, Yoichi; Kondo, Yuki; Irie, Tetsumi; Era, Takumi

    2015-01-01

    Summary The Niemann–Pick type C disease (NPC) is one of inherited lysosomal storage disorders, emerges the accumulation of unesterified cholesterol in endolysosomes. Currently, 2-hydroxypropyl-β-cyclodextrin (HP-β-CyD) has been applied for the treatment of NPC. HP-β-CyD improved hepatosplenomegaly in NPC patients, however, a high dose of HP-β-CyD was necessary. Therefore, the decrease in dose by actively targeted-β-CyD to hepatocytes is expected. In the present study, to deliver β-CyD selectively to hepatocytes, we newly fabricated mono-lactose-appended β-CyD (Lac-β-CyD) and evaluated its cholesterol lowering effects in NPC-like HepG2 cells, cholesterol accumulated HepG2 cells induced by treatment with U18666A. Lac-β-CyD (degree of substitution of lactose (DSL) 1) significantly decreased the intracellular cholesterol content in a concentration-dependent manner. TRITC-Lac-β-CyD was associated with NPC-like HepG2 cells higher than TRITC-β-CyD. In addition, TRITC-Lac-β-CyD was partially localized with endolysosomes after endocytosis. Thus, Lac-β-CyD entered NPC-like HepG2 cells via asialoglycoprotein receptor (ASGPR)-mediated endocytosis and decreased the accumulation of intracellular cholesterol in NPC-like HepG2 cells. These results suggest that Lac-β-CyD may have the potential as a drug for the treatment of hepatosplenomegaly in NPC disease. PMID:26664628

  19. Chronic Noise Exposure Acts Cumulatively to Exacerbate Alzheimer’s Disease-Like Amyloid-β Pathology and Neuroinflammation in the Rat Hippocampus

    PubMed Central

    Cui, Bo; Li, Kang; Gai, Zhihui; She, Xiaojun; Zhang, Na; Xu, Chuanxiang; Chen, Xuewei; An, Gaihong; Ma, Qiang; Wang, Rui

    2015-01-01

    A putative etiological association exists between noise exposure and Alzheimer’s disease (AD). Amyloid-β (Aβ) pathology is thought to be one of the primary initiating factors in AD. It has been further suggested that subsequent dysregulation of Aβ may play a mechanistic role in the AD-like pathophysiology associated with noise exposure. Here, we used ELISA, immunoblotting, cytokine arrays, and RT-PCR, to examine both hippocampal Aβ pathology and neuroinflammation in rats at different time points after noise exposure. We found that chronic noise exposure significantly accelerated the progressive overproduction of Aβ, which persisted for 7 to 14 days after the cessation of exposure. This effect was accompanied by up-regulated expression of amyloid precursor protein (APP) and its cleavage enzymes, β- and γ-secretases. Cytokine analysis revealed that chronic noise exposure increased levels of tumor necrosis factor-α and the receptor for advanced glycation end products, while decreasing the expression of activin A and platelet-derived growth factor- AA. Furthermore, we found persistent elevations of glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 expression that closely corresponded to the noise-induced increases in Aβ and neuroinflammation. These studies suggest that lifelong environmental noise exposure may have cumulative effects on the onset and development of AD. PMID:26251361

  20. Memantine combined with environmental enrichment improves spatial memory and alleviates Alzheimer's disease-like pathology in senescence-accelerated prone-8 (SAMP8) mice

    PubMed Central

    Dong, Jingde; Zhou, Mi; Wu, Xiaoqiang; Du, Mingyang; Wang, Xiaoshan

    2012-01-01

    Memantine is a N-methyl-D-aspartate (NMDA) receptor antagonist approved for the treatment of moderate to severe Alzheimer's disease (AD). Environmental enrichment (EE) has shown significant beneficial effects on functional improvement in AD. In this study, we sought to determine whether combining these two distinct therapies would yield greater benefit than either drug used alone. We investigated the effect of memantine combined with EE on spatial learning and memory and AD-like pathology in a widely used AD model, the senescence-accelerated prone mice (SAMP8). The SAMP8 mice were randomly assigned to enriched housing (EH) or standard housing (SH), where either memantine (20 mg/kg) or saline was given by gastric lavage once daily continuously for eight weeks. Our results showed that, when provided separately, memantine and EE significantly improved spatial learning and memory by shortening escape latencies and increasing the frequency of entrance into the target quadrant. When combined, memantine and EE showed additive effect on learning and memory as evidenced by significant shorter escape latencies and higher frequency of target entrance than either drug alone. Consistent with the behavior results, pathological studies showed that both memantine and EE significantly reduced hippocampal CA1 neurofibrilliary tangles (NFTs) as well as amyloid beta precursor protein (APP) levels. Combining both therapies synergistically lessened NFTs and APP expression compared to either drug alone in SAMP8 mice, indicating that the combination of memantine with EE could offer a novel and efficient therapeutic strategy for the treatment of AD. PMID:23554783

  1. The misfolded pro-inflammatory protein S100A9 disrupts memory via neurochemical remodelling instigating an Alzheimer's disease-like cognitive deficit.

    PubMed

    Gruden, Marina A; Davydova, Tatiana V; Wang, Chao; Narkevich, Victor B; Fomina, Valentina G; Kudrin, Vladimir S; Morozova-Roche, Ludmilla A; Sewell, Robert D E

    2016-06-01

    Memory deficits may develop from a variety of neuropathologies including Alzheimer's disease dementia. During neurodegenerative conditions there are contributory factors such as neuroinflammation and amyloidogenesis involved in memory impairment. In the present study, dual properties of S100A9 protein as a pro-inflammatory and amyloidogenic agent were explored in the passive avoidance memory task along with neurochemical assays in the prefrontal cortex and hippocampus of aged mice. S100A9 oligomers and fibrils were generated in vitro and verified by AFM, Thioflavin T and A11 antibody binding. Native S100A9 as well as S100A9 oligomers and fibrils or their combination were administered intranasally over 14 days followed by behavioral and neurochemical analysis. Both oligomers and fibrils evoked amnestic activity which correlated with disrupted prefrontal cortical and hippocampal dopaminergic neurochemistry. The oligomer-fibril combination produced similar but weaker neurochemistry to the fibrils administered alone but without passive avoidance amnesia. Native S100A9 did not modify memory task performance even though it generated a general and consistent decrease in monoamine levels (DA, 5-HT and NA) and increased metabolic marker ratios of DA and 5-HT turnover (DOPAC/DA, HVA/DA and 5-HIAA) in the prefrontal cortex. These results provide insight into a novel pathogenetic mechanism underlying amnesia in a fear-aggravated memory task based on amyloidogenesis of a pro-inflammatory factor leading to disrupted brain neurochemistry in the aged brain. The data further suggests that amyloid species of S100A9 create deleterious effects principally on the dopaminergic system and this novel finding might be potentially exploited during dementia management through a neuroprotective strategy. PMID:26965570

  2. Minocycline modulates neuroprotective effect of hesperidin against quinolinic acid induced Huntington's disease like symptoms in rats: behavioral, biochemical, cellular and histological evidences.

    PubMed

    Kumar, Anil; Chaudhary, Tanya; Mishra, Jitendriya

    2013-11-15

    Emerging evidences indicate hesperidin, a citrus flavanone, attenuates neurodegenerative processes and related complications. Besides its anti-oxidant properties, the other probable mechanisms which underpin its neuroprotective potential are still not clear. In light of emerging role of flavonoids in modulating oxidative stress and neuro-inflammation, the study has been designed to explore the possible neuroprotective effect of hesperidin and its combination with minocycline (microglial inhibitor), against quinolinic acid (QA) induced Huntington's disease (HD) like symptoms in rats. Unilateral intrastriatal administration of QA (300 nmol/4 µl) significantly reduced body weight, impaired behavior (locomotor activity, beam balance and memory performance), caused oxidative damage (increased lipid peroxidation, nitrite concentration, depleted super oxide dismutase and reduced glutathione), demonstrated mitochondrial dysfunction (decreased Complex-I, II, III, and IV activities), increased striatal lesion volume and altered the levels of TNF-α, caspase-3 as well as BDNF expression, as compared to sham group. Meanwhile, chronic hesperidin (100mg/kg, p.o.) and minocycline (25mg/kg, p.o.) treatment for 21 days significantly attenuated the behavioral, biochemical and cellular alterations as compared to QA treated (control) animals, whereas hesperidin (50mg/kg, p.o.) treatment was found to be non-significant. However, treatment of hesperidin (50mg/kg) in combination with minocycline (25mg/kg) potentiated their neuroprotective effect, which was significant as compared to their effects per se in QA treated animals. Taken altogether, the results of the present study suggest a possible interplay of microglial modulation and anti-oxidant effect in neuroprotective potential of hesperidin against QA induced HD like symptoms in rats. PMID:24211676

  3. Corticotropin-releasing factor receptor 1 activation during exposure to novelty stress protects against Alzheimer's disease-like cognitive decline in AβPP/PS1 mice.

    PubMed

    Scullion, Gillian A; Hewitt, Katherine N; Pardon, Marie-Christine

    2013-01-01

    A lifestyle rich in physical and mental activities protects against Alzheimer's disease (AD) but the underlying mechanisms are unclear. We have proposed that this is mediated by a stress response and have shown that repeated exposure to novelty stress, which induces physical and exploratory activities, delays the progression of AD-like pathology in the TASTPM mouse model. Here, we aimed to establish the role played by corticotrophin-releasing factor receptor 1 (CRFR1), a major component of the stress axis, in TASTPM's behavioral and neuroendocrine responses to novelty and related protective effects. We show that the stress response of TASTPM mice is altered with reduced CRFR1-mediated neuroendocrine and behavioral responses to novelty and a distinct profile of behavioral responses. Repeated novelty-induced CRFR1 activation, however, mediated the improved contextual fear memory and extinction performance of TASTPM mice and increased hippocampal and fronto-cortical levels of synaptophysin, a marker of synaptic density, and fronto-cortical levels of the post-synaptic marker PSD95. The N-methyl-D-aspartate receptor (NMDAR) is the major receptor for synaptic plasticity underlying learning and memory. Although novelty-induced NMDAR activation contributed to enhancement of fear memory and synaptophysin levels, antagonism of CRFR1 and NMDAR prevented the novelty-induced increase in hippocampal synaptophysin levels but reversed the other effects of CRFR1 inactivation, i.e., the enhancement of contextual fear extinction and fronto-cortical synaptophysin and PSD95 levels. These findings suggest a novel mechanism whereby a stimulating environment can delay AD symptoms through CRFR1 activation, facilitating NMDAR-mediated synaptic plasticity and synaptogenesis in a region-dependent manner, either directly, or indirectly, by modulating PSD95. PMID:23302658

  4. TrkB reduction exacerbates Alzheimer's disease-like signaling aberrations and memory deficits without affecting β-amyloidosis in 5XFAD mice

    PubMed Central

    Devi, L; Ohno, M

    2015-01-01

    Accumulating evidence shows that brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase B (TrkB) significantly decrease early in Alzheimer's disease (AD). However, it remains unclear whether BDNF/TrkB reductions may be mechanistically involved in the pathogenesis of AD. To address this question, we generated 5XFAD transgenic mice with heterozygous TrkB knockout (TrkB+/–·5XFAD), and tested the effects of TrkB reduction on AD-like features in this mouse model during an incipient stage that shows only modest amyloid-β (Aβ) pathology and retains normal mnemonic function. TrkB+/– reduction exacerbated memory declines in 5XFAD mice at 4–5 months of age as assessed by the hippocampus-dependent spontaneous alternation Y-maze task, while the memory performance was not affected in TrkB+/– mice. Meanwhile, TrkB+/–·5XFAD mice were normal in nest building, a widely used measure for social behavior, suggesting the memory-specific aggravation of AD-associated behavioral impairments. We found no difference between TrkB+/–·5XFAD and 5XFAD control mice in cerebral plaque loads, Aβ concentrations including total Aβ42 and soluble oligomers and β-amyloidogenic processing of amyloid precursor protein. Interestingly, reductions in hippocampal expression of AMPA/NMDA glutamate receptor subunits as well as impaired signaling pathways downstream to TrkB such as CREB (cAMP response element-binding protein) and Akt/GSK-3β (glycogen synthase kinase-3β) were observed in TrkB+/–·5XFAD mice but not in 5XFAD mice. Among these signaling aberrations, only Akt/GSK-3β dysfunction occurred in TrkB+/– mice, while others were synergistic consequences between TrkB reduction and subthreshold levels of Aβ in TrkB+/–·5XFAD mice. Collectively, our results indicate that reduced TrkB does not affect β-amyloidosis but exacerbates the manifestation of hippocampal mnemonic and signaling dysfunctions in early AD. PMID:25942043

  5. 77 FR 18248 - Agency for Toxic Substances and Disease Registry; Agency Forms Undergoing Paperwork Reduction Act...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-27

    ... HUMAN SERVICES Agency for Toxic Substances and Disease Registry; Agency Forms Undergoing Paperwork Reduction Act Review The Centers for Disease Control and Prevention (CDC) publishes a list of information... in the Navajo Nation--New--Agency for Toxic Substances and Disease Registry (ATSDR) and Centers...

  6. Protective Effects of Streblus asper Leaf Extract on H2O2-Induced ROS in SK-N-SH Cells and MPTP-Induced Parkinson's Disease-Like Symptoms in C57BL/6 Mouse

    PubMed Central

    Singsai, Kanathip; Akaravichien, Tarinee; Kukongviriyapan, Veerapol; Sattayasai, Jintana

    2015-01-01

    This study investigated the effects of Streblus asper leaf extract (SA) on reactive oxygen species (ROS) in SK-N-SH cell culture and on motor functions and behaviors in MPTP-treated C57BL/6 mice. SK-N-SH cell viability after incubation with SA for 24 h was measured by MTT assay. Intracellular ROS levels of SK-N-SH cells were quantified after pretreatment with SA (0, 200, 600, and 1000 µg/mL) in the presence of H2O2 (300 µM). Male C57BL/6 mice were force-fed with water or 200 mg/kg/day SA for 32 days. Intraperitoneal injection of MPTP was used to induce Parkinson's disease-like symptoms. Catalepsy, beam balance ability, olfactory discrimination, social recognition, and spontaneous locomotor activity were assessed on days 19, 21, 23, 26, and 32, respectively. In cell culture, SA at 200, 600, and 1000 µg/mL significantly decreased ROS levels in H2O2-treated SK-N-SH cells. MPTP-treated C57BL/6 mice showed a significant change in all parameters tested when compared to the control group. Pretreatment and concurrent treatment with 200 mg/kg/day SA could antagonize the motor and cognitive function deficits induced by MPTP. The results show that SA possesses anti-Parkinson effects in MPTP-treated C57BL/6 mice and that reduction in ROS levels might be one of the mechanisms. PMID:26798403

  7. Myenteric plexitis: A frequent feature in patients undergoing surgery for colonic diverticular disease

    PubMed Central

    Villanacci, Vincenzo; Sidoni, Angelo; Nascimbeni, Riccardo; Dore, Maria P; Binda, Gian A; Bandelloni, Roberto; Salemme, Marianna; Del Sordo, Rachele; Cadei, Moris; Manca, Alessandra; Bernardini, Nunzia; Maurer, Christoph A; Cathomas, Gieri

    2015-01-01

    Background Diverticular disease of the colon is frequent in clinical practice, and a large number of patients each year undergo surgical procedures worldwide for their symptoms. Thus, there is a need for better knowledge of the basic pathophysiologic mechanisms of this disease entity. Objectives Because patients with colonic diverticular disease have been shown to display abnormalities of the enteric nervous system, we assessed the frequency of myenteric plexitis (i.e. the infiltration of myenteric ganglions by inflammatory cells) in patients undergoing surgery for this condition. Methods We analyzed archival resection samples from the proximal resection margins of 165 patients undergoing left hemicolectomy (60 emergency and 105 elective surgeries) for colonic diverticulitis, by histology and immunochemistry. Results Overall, plexitis was present in almost 40% of patients. It was subdivided into an eosinophilic (48%) and a lymphocytic (52%) subtype. Plexitis was more frequent in younger patients; and it was more frequent in those undergoing emergency surgery (50%), compared to elective (28%) surgery (p = 0.007). All the severe cases of plexitis displayed the lymphocytic subtype. Conclusions In conclusion, myenteric plexitis is frequent in patients with colonic diverticular disease needing surgery, and it might be implicated in the pathogenesis of the disease. PMID:26668745

  8. [Determinants of vascular wall stiffness in patients with chronic renal disease undergoing hemodialysis].

    PubMed

    Kharlamova, U V; Il'icheva, O E

    2012-01-01

    Examination of 109 patients with chronic renal disease undergoing hemodialysis revealed significant impairment of arterial wall distensibility (accordingly, decreased Peterson's and Young's elastic moduli, distensibility coefficient). The relative thickness of the common carotid artery and pulse wave velocity were significantly greater than in practically healthy subjects. Independent factors influencing arterial wall rigidity included age, arterial pressure, total cholesterol and homocystein, stable metabolites of nitric oxide, creatinine, calcium, phosphorus levels, calcium x phosphorus product, duration of hemodialysis, interdialytic weight gain. PMID:23516853

  9. On-treatment platelet reactivity in patients with chronic obstructive pulmonary disease undergoing percutaneous coronary intervention.

    PubMed

    Campo, Gianluca; Pavasini, Rita; Pollina, Alberto; Tebaldi, Matteo; Ferrari, Roberto

    2014-01-01

    Patients with chronic obstructive pulmonary disease (COPD) show a poor prognosis after myocardial infarction (MI) and percutaneous coronary intervention (PCI). We evaluated on-treatment platelet reactivity (PR) and several gene polymorphisms related to PR in 130 patients undergoing PCI with and without COPD. Those with concomitant COPD showed higher on-treatment PR values both at the time of PCI and 1 month after. This finding may contribute to explain the poor prognosis of COPD patients after MI and PCI. PMID:23878160

  10. Effectively Screening for Coronary Artery Disease in Patients Undergoing Orthotopic Liver Transplant Evaluation

    PubMed Central

    Li, Feng; Hanje, Adam J.; Mumtaz, Khalid; Boudoulas, Konstantinos D.; Lilly, Scott M.

    2016-01-01

    Coronary artery disease (CAD) is prevalent in patients with end-stage liver disease and associated with poor outcomes when undergoing orthotopic liver transplantation (OLT); however, noninvasive screening for CAD in this population is less sensitive. In an attempt to identify redundancy, we reviewed our experience among patients undergoing CAD screening as part of their OLT evaluation between May 2009 and February 2014. Demographic, clinical, and procedural characteristics were analyzed. Of the total number of screened patients (n = 132), initial screening was more common via stress testing (n = 100; 75.8%) than coronary angiography (n = 32; 24.2%). Most with initial stress testing underwent angiography (n = 52; 39.4%). Among those undergoing angiography, CAD was common (n = 31; 23.5%). Across the entire cohort the number of traditional risk factors was linearly associated with CAD, and those with two or more risk factors were found to have CAD by angiography 50% of the time (OR 1.92; CI 1.07–3.44, p = 0.026). Our data supports that CAD is prevalent among pre-OLT patients, especially among those with 2 or more risk factors. Moreover, we identified a lack of uniformity in practice and the need for evidence-based and standardized screening protocols. PMID:27418975

  11. Peripheral artery disease in korean patients undergoing percutaneous coronary intervention: prevalence and association with coronary artery disease severity.

    PubMed

    Kim, Eun Kyoung; Song, Pil Sang; Yang, Jeong Hoon; Song, Young Bin; Hahn, Joo-Yong; Choi, Jin-Ho; Gwon, Hyeon-Cheol; Lee, Sang Hoon; Hong, Kyung Pyo; Park, Jeong Euy; Kim, Duk-kyung; Choi, Seung-Hyuk

    2013-01-01

    Peripheral artery disease (PAD) is an important marker for the risk stratification of patients with coronary artery disease (CAD). We investigated the prevalence of PAD in patients undergoing percutaneous coronary intervention (PCI) with CAD and the relationship between ankle-brachial pressure index (ABPI) and CAD severity. A total of 711 patients undergoing PCI for CAD from August 2009 to August 2011 were enrolled. PAD diagnosis was made using the ABPI. The prevalence of PAD was 12.8%. In PAD patients, mean values of right and left ABPI were 0.71 ± 0.15 and 0.73 ± 0.15. Patients with PAD had a higher prevalence of left main coronary disease (14.3% vs 5.8%, P = 0.003), more frequently had multivessel lesions (74.9% vs 52.1%, P < 0.001) and had higher SYNTAX score (18.2 ± 12.3 vs 13.1 ± 8.26, P = 0.002). Using multivariate analysis, we determined that left main CAD (OR, 2.954; 95% CI, 1.418-6.152, P = 0.004) and multivessel CAD (OR, 2.321; 95% CI, 1.363-3.953, P = 0.002) were both independently associated with PAD. We recommend that ABPI-based PAD screening should be implemented in all patients undergoing PCI with CAD, especially in severe cases. PMID:23341717

  12. A systematic review of sleep disorders in patients with chronic kidney disease undergoing hemodialysis.

    PubMed

    Fonseca, Nina Teixeira; Urbano, Jessica Julioti; Nacif, Sergio Roberto; Silva, Anderson Soares; Peixoto, Roger Andre Oliveira; Urbano, Giovanni Julioti; Oliveira, Ezequiel Fernandes; Santos, Israel Reis; Oliveira, Claudia Santos; Insalaco, Giuseppe; Oliveira, Luis Vicente Franco

    2016-07-01

    The purpose of this study was to conduct a systematic review of the available evidence on sleep disorders in patients with end stage renal disease (ESRD) undergoing hemodialysis (HD). [Subjects and Methods] Two independent reviewers performed a computer-assisted search of the MEDLINE, SciELO, LILACS, and BIREME Virtual Health Library medical databases from their inception to November 2015. [Results] One thousand one hundred twenty-six articles were found that met the inclusion criteria. Articles were excluded if they were not in English, the patients did not undergo HD, or the studies were not cross-sectional or clinical trials. After reading the full text, a further 300 studies were excluded because they did not use polysomnography. The remaining 18 studies with ESRD patients undergoing HD comprised 8 clinical trials and 10 cross-sectional studies. This systematic review followed the criteria outlined by the PRISMA declaration. [Conclusion] In this systematic review, a high prevalence of sleep disorders was observed in ESRD, including sleep-disordered breathing. This knowledge may enable health professionals to devise new strategies for the diagnosis and treatment of these patients, in order to reduce morbidity and mortality and improve their quality of life. PMID:27512289

  13. Hospital Costs and Inpatient Mortality among Children Undergoing Surgery for Congenital Heart Disease

    PubMed Central

    Romley, John A; Chen, Alex Y; Goldman, Dana P; Williams, Roberta

    2014-01-01

    Objective To determine the association between hospital costs and risk-adjusted inpatient mortality among children undergoing surgery for congenital heart disease (CHD) in U.S. acute-care hospitals. Data Sources/Study Settings Retrospective cohort study of 35,446 children in 2003, 2006, and 2009 Kids' Inpatient Database (KID). Study Design Cross-sectional logistic regression of risk-adjusted inpatient mortality and hospital costs, adjusting for a variety of patient-, hospital-, and community-level confounders. Data Collection/Extraction Methods We identified relevant discharges in the KID using the AHRQ Pediatric Quality Indicator for pediatric heart surgery mortality, and linked these records to hospital characteristics from American Hospital Association Surveys and community characteristics from the Census. Principal Findings Children undergoing CHD surgery in higher cost hospitals had lower risk-adjusted inpatient mortality (p = .002). An increase from the 25th percentile of treatment costs to the 75th percentile was associated with a 13.6 percent reduction in risk-adjusted mortality. Conclusions Greater hospital costs are associated with lower risk-adjusted inpatient mortality for children undergoing CHD surgery. The specific mechanisms by which greater costs improve mortality merit further exploration. PMID:24138064

  14. A systematic review of sleep disorders in patients with chronic kidney disease undergoing hemodialysis

    PubMed Central

    Fonseca, Nina Teixeira; Urbano, Jessica Julioti; Nacif, Sergio Roberto; Silva, Anderson Soares; Peixoto, Roger Andre Oliveira; Urbano, Giovanni Julioti; Oliveira, Ezequiel Fernandes; Santos, Israel Reis; Oliveira, Claudia Santos; Insalaco, Giuseppe; Oliveira, Luis Vicente Franco

    2016-01-01

    The purpose of this study was to conduct a systematic review of the available evidence on sleep disorders in patients with end stage renal disease (ESRD) undergoing hemodialysis (HD). [Subjects and Methods] Two independent reviewers performed a computer-assisted search of the MEDLINE, SciELO, LILACS, and BIREME Virtual Health Library medical databases from their inception to November 2015. [Results] One thousand one hundred twenty-six articles were found that met the inclusion criteria. Articles were excluded if they were not in English, the patients did not undergo HD, or the studies were not cross-sectional or clinical trials. After reading the full text, a further 300 studies were excluded because they did not use polysomnography. The remaining 18 studies with ESRD patients undergoing HD comprised 8 clinical trials and 10 cross-sectional studies. This systematic review followed the criteria outlined by the PRISMA declaration. [Conclusion] In this systematic review, a high prevalence of sleep disorders was observed in ESRD, including sleep-disordered breathing. This knowledge may enable health professionals to devise new strategies for the diagnosis and treatment of these patients, in order to reduce morbidity and mortality and improve their quality of life. PMID:27512289

  15. Prediction of coronary artery disease in patients undergoing operations for mitral valve degeneration

    NASA Technical Reports Server (NTRS)

    Lin, S. S.; Lauer, M. S.; Asher, C. R.; Cosgrove, D. M.; Blackstone, E.; Thomas, J. D.; Garcia, M. J.

    2001-01-01

    OBJECTIVES: We sought to develop and validate a model that estimates the risk of obstructive coronary artery disease in patients undergoing operations for mitral valve degeneration and to demonstrate its potential clinical utility. METHODS: A total of 722 patients (67% men; age, 61 +/- 12 years) without a history of myocardial infarction, ischemic electrocardiographic changes, or angina who underwent routine coronary angiography before mitral valve prolapse operations between 1989 and 1996 were analyzed. A bootstrap-validated logistic regression model on the basis of clinical risk factors was developed to identify low-risk (< or =5%) patients. Obstructive coronary atherosclerosis was defined as 50% or more luminal narrowing in one or more major epicardial vessels, as determined by means of coronary angiography. RESULTS: One hundred thirty-nine (19%) patients had obstructive coronary atherosclerosis. Independent predictors of coronary artery disease include age, male sex, hypertension, diabetes mellitus,and hyperlipidemia. Two hundred twenty patients were designated as low risk according to the logistic model. Of these patients, only 3 (1.3%) had single-vessel disease, and none had multivessel disease. The model showed good discrimination, with an area under the receiver-operating characteristic curve of 0.84. Cost analysis indicated that application of this model could safely eliminate 30% of coronary angiograms, corresponding to cost savings of $430,000 per 1000 patients without missing any case of high-risk coronary artery disease. CONCLUSION: A model with standard clinical predictors can reliably estimate the prevalence of obstructive coronary atherosclerosis in patients undergoing mitral valve prolapse operations. This model can identify low-risk patients in whom routine preoperative angiography may be safely avoided.

  16. Prevalence of renal artery disease and its prognostic significance in patients undergoing coronary bypass grafting.

    PubMed

    Aboyans, Victor; Tanguy, Benedicte; Desormais, Ileana; Bonnet, Vincent; Chonchol, Michel; Laskar, Marc; Mohty, Dania; Lacroix, Philippe

    2014-10-01

    Several studies demonstrated the prognostic importance of renal failure and peripheral artery disease in patients undergoing coronary artery bypass grafting (CABG), but data regarding the prognostic value of renal artery disease in this context are scarce. We aimed to study the prevalence and prognostic value of renal artery disease in patients undergoing CABG. We assessed by duplex ultrasound the renal arteries of 429 consecutive patients who underwent CABG, of whom 401 had satisfactory imaging quality to detect >60% renal artery stenosis (RAS) and/or an elevated resistive index (ERI>0.80). Of the 401 subjects included (age 68±10 years, 83% men), 40 (10%) had RAS and 35 (9%) had ERI. Nine patients (2.2%) had both conditions. Patients were followed up for 12.4±7.0 months. The primary outcome was composite, including 30-day death, stroke, and/or myocardial infarction. In a multivariate model adjusted for age, gender, cardiovascular (CV) risk factors, renal function, chronic obstructive pulmonary disease, the use of off-pump CABG, CV co-morbidities, and drugs, the presence of ERI was strongly associated with the occurrence of the composite outcome (odds ratio 4.3, 95% confidence interval 1.7 to 9.9, p=0.0006). Similarly, ERI, not RAS, was significantly associated with the 30-day acute kidney disease and the midterm mortality, as well as fatal and nonfatal CV events. In conclusion, regardless of renal function and other factors, the renal resistive index is a strong predictor of CV and renal events after CABG. Renal duplex ultrasound can identify a subgroup of patients at high risk of CABG. PMID:25150754

  17. Increased Coronary Artery Disease Severity in Black Women Undergoing Coronary Bypass Surgery

    PubMed Central

    Efird, Jimmy T.; O’Neal, Wesley T.; Griffin, William F.; Anderson, Ethan J.; Davies, Stephen W.; Landrine, Hope; O’Neal, Jason B.; Shiue, Kristin Y.; Kindell, Linda C.; Bruce Ferguson, T.; Randolph Chitwood, W.; Kypson, Alan P.

    2015-01-01

    Abstract Race and sex disparities are believed to play an important role in heart disease. The purpose of this study was to examine the association between race, sex, and number of diseased vessels at the time of coronary artery bypass grafting (CABG), and subsequent postoperative outcomes. The 13,774 patients undergoing first-time, isolated CABG between 1992 and 2011 were included. Trend in the number of diseased vessels between black and white patients, stratified by sex, were analyzed using a Cochran–Armitage trend test. Models were adjusted for age, procedural status (elective vs. nonelective), and payor type (private vs. nonprivate insurance). Black female CABG patients presented with an increasingly greater number of diseased vessels than white female CABG patients (adjusted Ptrend = 0.0021). A similar trend was not observed between black and white male CABG patients (adjusted Ptrend = 0.18). Black female CABG patients were also more likely to have longer intensive care unit and hospital lengths of stay than other race–sex groups. Our findings suggest that black female CABG patients have more advanced coronary artery disease than white female CABG patients. Further research is needed to determine the benefit of targeted preventive care and preoperative workup for this high-risk group. PMID:25700324

  18. Anxiety determinants in mothers of children with congenital heart diseases undergoing cardiac surgery

    PubMed Central

    Rahimianfar, Ali Akbar; Forouzannia, Seyed Khalil; Sarebanhassanabadi, Mohammadtaghi; Dehghani, Hamide; Namayandeh, Syedeh Mahdieh; Khavary, Zohre; Rahimianfar, Fatemeh; Aghbageri, Hamid

    2015-01-01

    Background: The infants with congenital cardiovascular diseases are faced with too much problems in the case of their ongoing life. Mothers’ stress investigation would be important because can receive the stress from his parents. The aim of the following study was determined anxiety in mothers of children undergoing cardiac surgery. Materials and Methods: The present study was conducted by an analytical study on 69 infants’ mothers who were operated due to their cardiovascular abnormalities in Yazd Afshar Hospital (2012). In this study, some demographic information and influential factors were recorded germane to mothers’ stress, including residential location, history of infant hospitalization or congenital disease as well as some questions in the case of stimuli of the hospital environment, family support, economic situation and the mothers’ awareness of their stress. Results: There are statistically significant differences between mothers’ stress and their age (P = 0.03) and infants’ age (P < 0.0001). There are not statically significant differences between mothers’ stress score mean and their educational level (P = 0.75), the infants’ hospitalization history (P = 0.57), the history of congenital of disease in family (P = 0.24) and the family support in infant care (P = 0.08). Conclusion: Those mothers who asserted the stimuli of the hospital environment, infant and its mother support, economic situation and the mothers’ awareness lack of disease and infant status as strong stress-making stimuli enjoy a stress high mean. PMID:26918237

  19. Determinants of Mortality in Patients with Chronic Kidney Disease Undergoing Percutaneous Coronary Intervention

    PubMed Central

    Papachristidis, Alexandros; Lim, Wei Yao; Voukalis, Christos; Ayis, Salma; Laing, Christopher; Rakhit, Roby D.

    2016-01-01

    Background Renal impairment is a known predictor of mortality in both the general population and in patients with cardiac disease. The aim of this study was to evaluate factors that determine mortality in patients with chronic kidney disease (CKD) who have undergone percutaneous coronary intervention (PCI). Methods In this study we included 293 consecutive patients with CKD who underwent PCI between 1st January 2007 and 30th September 2012. The primary outcome that we studied was all-cause mortality in a follow-up period of 12-69 months (mean 38.8 ± 21.7). Results Age (p < 0.001), PCI indication (p = 0.035), CKD stage (p < 0.001) and left ventricular ejection fraction (p < 0.001) were significantly related to mortality. CKD stage 5 [hazard ratio (HR) = 6.39, 95% CI: 1.51-27.12) and severely impaired left ventricular function (HR = 4.04, 95% CI: 2.15-7.59) were the strongest predictors of mortality. Other factors tested (gender, hypertension, diabetes, hyperlipidaemia, established peripheral vascular disease/stroke, coronary arteries intervened, number of vessels treated, number of stents implanted and length of lesion treated) did not show any correlation with mortality. Conclusions The mortality of patients with CKD undergoing PCI increases with age, worsening CKD stage and deteriorating left ventricular systolic function, and it is also higher in patients with acute coronary syndromes compared to those with stable coronary artery disease.

  20. Prevalence and correlates of Willis-Ekbom's disease/restless legs syndrome in patients undergoing hemodialysis.

    PubMed

    Bathla, Nitik; Ahmad, Sohaib; Gupta, Ravi; Ahmad, Shahbaj

    2016-01-01

    Willis-Ekbom's disease/restless legs syndrome (WED/RLS) has been described in subjects undergoing hemodialysis (HD). Different studies have reported varying prevalence rates and different factors associated with this condition; however, the results are inconsistent. Thus, this study was conducted to assess the prevalence of WED/RLS in patients undergoing HD. Another aim of the study was to identify if any comorbidities or biochemical factors were associated with this condition. A total of 194 adult patients undergoing maintenance HD were included in this study. They were screened for WED/RLS using International RLS Study Group criteria on the face-to-face interview and clinical examination. Most recent laboratory parameters were gathered from the medical records. In addition, seroreactivity to hepatitis B and C was also recorded. The mean age of all the subjects included in the study was 54.4 ± 15 years (range: 18-92 years); 58.2% were males. The mean duration on HD was 36.6 ± 19.3 months. WED/RLS was seen in 5.2% of the study subjects. Subjects with and without WED/RLS were comparable with regard to gender (P = 0.23), adequacy of dialysis (P = 0.82), shift of dialysis (P = 0.93), presence of diabetes mellitus (P = 0.91), hypertension (P = 0.26), smoking (P = 0.22), alcohol use (P = 0.45), and reactivity to hepatitis C (P = 0.19) and hepatitis B (P = 0.80), as well as various hematological and biochemical parameters. The prevalence of WED/RLS of 5% in the HD group was higher than in the general population. However, this study could not find any correlation between RLS and any biochemical parameters or comorbidities. This is an important area to be considered in future and requires more work with larger sample size. PMID:27424684

  1. Risk of Bleeding in End-Stage Liver Disease Patients Undergoing Cardiac Catheterization

    PubMed Central

    Mahmoud, Ahmed M.; Elgendy, Islam Y.; Choi, Calvin Y.

    2015-01-01

    Patients with end-stage liver disease frequently have baseline coagulopathies. The international normalized ratio is in common use for the estimation of bleeding tendency in such patients, especially those undergoing an invasive procedure like cardiac catheterization. The practice of international normalized ratio measurement—followed by pharmacologic (for example, vitamin K or fresh frozen plasma) or nonpharmacologic intervention—is still debatable. The results of multiple randomized trials have shown the superiority of the radial approach over femoral access in reducing catheterization bleeding. This reduction in bleeding in turn decreases the risk and cost of blood-product transfusion. However, there is little evidence regarding the use of the radial approach in the end-stage liver disease patient population specifically. In this review, we summarize the studies that have dealt with cardiac catheterization in patients who have end-stage liver disease. We also discuss the role of the current measurements that are used to reduce the risk of bleeding in these same patients. PMID:26504433

  2. Hope and spirituality among patients with chronic kidney disease undergoing hemodialysis: a correlational study1

    PubMed Central

    Ottaviani, Ana Carolina; Souza, Érica Nestor; Drago, Natália de Camargo; de Mendiondo, Marisa Silvana Zazzetta; Pavarini, Sofia Cristina Iost; Orlandi, Fabiana de Souza

    2014-01-01

    Objective to analyze the relationship between the hope and spirituality of patients with chronic kidney disease undergoing hemodialysis. Method this is a cross-sectional, correlational study. The sample was composed of 127 patients of a Renal Replacement Unit. Data were collected through individual interviews guided by the following instruments: participant characterization, Herth Hope Index (HHI), and Pinto Pais-Ribeiro Spirituality Scale (PP-RSS). Results the average HHI score was 38.06 (±4.32) while the average PP-RSS score was 3.67 (±0.62) for "beliefs" and 3.21 (±0.53) for "hope/optimism". Spearman's coefficient indicated there was a moderate positive correlation between the HHI and PP-RSS dimensions of "beliefs" (r=0.430; p<0.001) and "hope/optimism" (r=0.376; p<0.001). Conclusion Since a relationship between the sense of hope and spirituality of patients with chronic kidney disease was found, these constructs should be taken into account at the time health professionals deliver care to help patients coping with the disease and treatment. PMID:26107832

  3. Evolution of weight and height of children with congenital heart disease undergoing surgical treatment

    PubMed Central

    Peres, Murilo Bertazzo; Croti, Ulisses Alexandre; de Godoy, Moacir Fernandes; Marchi, Carlos Henrique De; Hassem Sobrinho, Sírio; Beani, Lilian; Moscardini, Airton Camacho; Braile, Domingo Marcolino

    2014-01-01

    Objective To evaluate the height and weight development of children with congenital heart disease undergoing surgery with the goal of determining when they reach the threshold of normal development and whether there are differences between patients with developmental pattern below the level of normality preoperatively (z-score<-2 for the analyzed parameter) in comparison to the total group of cardiac patients. Methods We prospectively followed up 27 children undergoing operation into five time periods: preoperatively and at four subsequent outpatient appointments: 1st month, 3rd month, 6th month and 12th month after hospital discharge. The anthropometric parameters used were median z-score (MZ), weight (WAZ), height (HAZ), subscapular skinfold (SSFAZ), upper arm circumference (UAC) and triceps skinfold (TSFAZ). The evolution assessment of the parameters was performed by analysis of variance and comparison with the general normal population from unpaired t test, both in the total group of cardiac patients, and in subgroups with preoperative parameters below the normal level (Zm<-2). Results In the total group there was no significant evolution of MZ of all parameters. WAZ was statistically lower than the normal population until the 1st month of follow-up (P=0.028); HAZ only preoperatively (P=0.044), SSFAZ in the first month (P=0.015) and at 12th month (P=0.038), UAC and TSFAZ were always statistically equal to the general population. In patients whose development was below the level of normality, there were important variation of WAZ (P=0.002), HAZ (P=0.001) and UAC (P=0.031) after the operation, and the WAZ was lower than the normal population until the 3rd month (P=0.015); HAZ and UAC, until the first month (P=0.024 and P=0.039 respectively), SSFAZ, up to the 12th month (P=0.005), the TSFAZ only preoperatively (P=0.011). Conclusion The operation promoted the return to normalcy for those with heart disease in general within up to three months, but for the group of

  4. An empowerment health education program for children undergoing surgery for congenital heart diseases.

    PubMed

    Ni, Zhihong; Chao, Yannfen; Xue, Xiaoling

    2016-09-01

    Since the surgery for congenital heart disease (CHD) is considered highly risky, appropriate postoperative care is crucial. After the surgery, children are often discharged with unhealed wounds, incomplete recovery, and continuing pain. Health education programs based on empowerment education model can assist clients to develop skills in self-management. This study aimed to evaluate the effectiveness of an empowerment health education program for improving caregiving knowledge, caring behaviors, and self-efficacy of parents caring for children after corrective surgery for CHD. This prospective clinical trial enrolled pediatric patients undergoing surgical correction for CHD. Patients were divided into two groups: the control group (n = 42), which received the standard education program, and the intervention group (n = 44), which participated in the empowerment theory-based education program. We collected data on left ventricular ejection fraction (LVEF); peripheral oxygen saturation (SpO2); New York Heart Association classification of the patients; and the parents' caregiving knowledge, caring behaviors, and self-efficacy before surgery and one month and three months after surgery. At one month and three months after surgery, the intervention group scored higher than the control group in caregiving knowledge, caring behavior, and self-efficacy. By the third month after surgery, the intervention group had significantly higher values of LVEF and SpO2 than the control group. PMID:26105060

  5. Prevalence of congenital heart disease in patients undergoing surgery for major gastrointestinal malformations: an Indian study

    PubMed Central

    Gokhroo, Rajendra K; Gupta, Sajal; Arora, Garima; Bisht, Devendra S; Padmanabhan, Deepak; Soni, Varsha

    2015-01-01

    Background The association of congenital heart disease (CHD) with malformations of the gastrointestinal (GI) tract/abdominal wall is known. The rates of cardiac malformations reported in previous studies of these anomalies are highly variable. Objective To find the prevalence and pattern of CHD in patients with major gastrointestinal malformations (anorectal malformations, oesophageal atresia/tracheo-oesophageal fistula, and omphalocoele) undergoing surgery at a tertiary care hospital in India. Methods From July 2012 to December 2013, 43 patients (34 (79%) male, 9 (21%) female) were evaluated by clinical examination, ECG, chest radiography, and colour Doppler echocardiography. Results Of the 43 patients, 26 (60.46%) had CHD. The most common GI malformation was anorectal malformation: 32 cases (74.41%), of whom 16 (50%) had CHD. The second most common malformation was oesophageal atresia/tracheo-oesophageal fistula: 5 cases (11.62%), all (100%) with CHD. The third group comprised patients with omphalocoele: 4 cases (9.3%), 3 of whom (75%) had CHD. The fourth group comprised patients with VACTERAL (vertebral anomalies, anal atresia, cardiovascular malformations, tracheo-oesophageal fistula, renal and limb anomalies) association—2 cases (4.6%), all (100%) with CHD. The most common CHD was isolated atrial septal defect (ASD) (73%), followed by ASD + ventricular septal defect (VSD) + patent ductus arteriosus (PDA) (7.6%), ASD + VSD (3.8%), ASD + PDA (3.8%), VSD (3.8%), PDA (3.8%), and coarctation of the aorta (3.8%). Conclusions We found the frequency of CHD in patients with GI malformations was very high, the most common presentation being ASD. Our study indicates the need for larger scale studies to determine the prevalence of CHD in patients with GI malformations in the Indian population. PMID:27326210

  6. A novel recombinant 6Aβ15-THc-C chimeric vaccine (rCV02) mitigates Alzheimer's disease-like pathology, cognitive decline and synaptic loss in aged 3 × Tg-AD mice.

    PubMed

    Yu, Yun-Zhou; Liu, Si; Wang, Hai-Chao; Shi, Dan-Yang; Xu, Qing; Zhou, Xiao-Wei; Sun, Zhi-Wei; Huang, Pei-Tang

    2016-01-01

    Alzheimer's disease (AD) is a neurodegenerative disorder that impairs memory and cognition. Targeting amyloid-β (Aβ) may be currently the most promising immunotherapeutic strategy for AD. In this study, a recombinant chimeric 6Aβ15-THc-C immunogen was formulated with alum adjuvant as a novel Aβ B-cell epitope candidate vaccine (rCV02) for AD. We examined its efficacy in preventing the cognitive deficit and synaptic impairment in 3 × Tg-AD mice. Using a toxin-derived carrier protein, the rCV02 vaccine elicited robust Aβ-specific antibodies that markedly reduced AD-like pathology and improved behavioral performance in 3 × Tg-AD mice. Along with the behavioral improvement in aged 3 × Tg-AD mice, rCV02 significantly decreased calpain activation concurrent with reduced soluble Aβ or oligomeric forms of Aβ, probably by preventing dynamin 1 and PSD-95 degradation. Our data support the hypothesis that reducing Aβ levels in rCV02-immunized AD mice increases the levels of presynaptic dynamin 1 and postsynaptic PSD-95 allowing functional recovery of cognition. In conclusion, this novel and highly immunogenic rCV02 shows promise as a new candidate prophylactic vaccine for AD and may be useful for generating rapid and strong Aβ-specific antibodies in AD patients with pre-existing memory Th cells generated after immunization with conventional tetanus toxoid vaccine. PMID:27255752

  7. A novel recombinant 6Aβ15-THc-C chimeric vaccine (rCV02) mitigates Alzheimer’s disease-like pathology, cognitive decline and synaptic loss in aged 3 × Tg-AD mice

    PubMed Central

    Yu, Yun-Zhou; Liu, Si; Wang, Hai-Chao; Shi, Dan-Yang; Xu, Qing; Zhou, Xiao-Wei; Sun, Zhi-Wei; Huang, Pei-Tang

    2016-01-01

    Alzheimer’s disease (AD) is a neurodegenerative disorder that impairs memory and cognition. Targeting amyloid-β (Aβ) may be currently the most promising immunotherapeutic strategy for AD. In this study, a recombinant chimeric 6Aβ15-THc-C immunogen was formulated with alum adjuvant as a novel Aβ B-cell epitope candidate vaccine (rCV02) for AD. We examined its efficacy in preventing the cognitive deficit and synaptic impairment in 3 × Tg-AD mice. Using a toxin-derived carrier protein, the rCV02 vaccine elicited robust Aβ-specific antibodies that markedly reduced AD-like pathology and improved behavioral performance in 3 × Tg-AD mice. Along with the behavioral improvement in aged 3 × Tg-AD mice, rCV02 significantly decreased calpain activation concurrent with reduced soluble Aβ or oligomeric forms of Aβ, probably by preventing dynamin 1 and PSD-95 degradation. Our data support the hypothesis that reducing Aβ levels in rCV02-immunized AD mice increases the levels of presynaptic dynamin 1 and postsynaptic PSD-95 allowing functional recovery of cognition. In conclusion, this novel and highly immunogenic rCV02 shows promise as a new candidate prophylactic vaccine for AD and may be useful for generating rapid and strong Aβ-specific antibodies in AD patients with pre-existing memory Th cells generated after immunization with conventional tetanus toxoid vaccine. PMID:27255752

  8. Crystal Structure of a Two-domain Fragment of Hepatocyte Growth Factor Activator Inhibitor-1: FUNCTIONAL INTERACTIONS BETWEEN THE KUNITZ-TYPE INHIBITOR DOMAIN-1 AND THE NEIGHBORING POLYCYSTIC KIDNEY DISEASE-LIKE DOMAIN.

    PubMed

    Hong, Zebin; De Meulemeester, Laura; Jacobi, Annemarie; Pedersen, Jan Skov; Morth, J Preben; Andreasen, Peter A; Jensen, Jan K

    2016-07-01

    Hepatocyte growth factor activator inhibitor-1 (HAI-1) is a type I transmembrane protein and inhibitor of several serine proteases, including hepatocyte growth factor activator and matriptase. The protein is essential for development as knock-out mice die in utero due to placental defects caused by misregulated extracellular proteolysis. HAI-1 contains two Kunitz-type inhibitor domains (Kunitz), which are generally thought of as a functionally self-contained protease inhibitor unit. This is not the case for HAI-1, where our results reveal how interdomain interactions have evolved to stimulate the inhibitory activity of an integrated Kunitz. Here we present an x-ray crystal structure of an HAI-1 fragment covering the internal domain and Kunitz-1. The structure reveals not only that the previously uncharacterized internal domain is a member of the polycystic kidney disease domain family but also how the two domains engage in interdomain interactions. Supported by solution small angle x-ray scattering and a combination of site-directed mutagenesis and functional assays, we show that interdomain interactions not only stabilize the fold of the internal domain but also stimulate the inhibitory activity of Kunitz-1. By completing our structural characterization of the previously unknown N-terminal region of HAI-1, we provide new insight into the interplay between tertiary structure and the inhibitory activity of a multidomain protease inhibitor. We propose a previously unseen mechanism by which the association of an auxiliary domain stimulates the inhibitory activity of a Kunitz-type inhibitor (i.e. the first structure of an intramolecular interaction between a Kunitz and another domain). PMID:27189939

  9. Cardiovascular disease risk factors and socioeconomic variables in a nation undergoing epidemiologic transition

    PubMed Central

    2013-01-01

    Background Cardiovascular disease (CVD) related deaths is not only the prime cause of mortality in the world, it has also continued to increase in the low and middle income countries. Hence, this study examines the relationship between CVD risk factors and socioeconomic variables in Malaysia, which is a rapidly growing middle income nation undergoing epidemiologic transition. Methods Using data from 11,959 adults aged 30 years and above, and living in urban and rural areas between 2007 and 2010, this study attempts to examine the prevalence of CVD risk factors, and the association between these factors, and socioeconomic and demographic variables in Malaysia. The socioeconomic and demographic, and anthropometric data was obtained with blood pressure and fasting venous blood for glucose and lipids through a community-based survey. Results The association between CVD risk factors, and education and income was mixed. There was a negative association between smoking and hypertension, and education and income. The association between diabetes, hypercholesterolemia and being overweight with education and income was not clear. More men than women smoked in all education and income groups. The remaining consistent results show that the relationship between smoking, and education and income was obvious and inverse among Malays, others, rural women, Western Peninsular Malaysia (WPM) and Eastern Peninsular Malaysia (EPM). Urban men showed higher prevalence of being overweight than rural men in all education and income categories. Except for those with no education more rural men smoked than urban men. Also, Malay men in all education and income categories showed the highest prevalence of smoking among the ethnic groups. Conclusions The association between CVD risk factors and socioeconomic variables should be considered when formulating programmes to reduce morbidity and mortality rates in low and middle income countries. While general awareness programmes should be targeted

  10. Thromboembolic disease in patients with rheumatoid arthritis undergoing joint arthroplasty: Update on prophylaxes

    PubMed Central

    Mameli, Antonella; Marongiu, Francesco

    2014-01-01

    The risk of venous thromboembolism (VTE) in rheumatoid arthritis (RA) and the higher incidence of RA patients undergoing major orthopedic surgery is well recognized. The objective of the present study is to describe the incidence of VTE and discuss the correct prophylaxis in RA patients undergoing knee or hip replacement. A systematic review of studies on thromboprophylaxis in RA patients undergoing major orthopedic surgery was performed. Detailed information was extracted to calculate the rate of VTE in RA orthopedic patients and analyze the thromboprophylaxis performed and bleeding complications. Eight articles were eligible for full review. No difference in the overall rate of VTE was observed between RA patients and controls. No significant differences were found in RA patients in terms of bleeding complications. The data on the optimal prophylaxis to be used in RA patients were insufficient to recommend any of the several options available. In the absence of dedicated guidelines for the care of RA patients undergoing orthopedic surgery, management must be individualized to obtain favorable patient outcome, weighing up all the factors that might put the patient at risk for higher bleeding and thrombotic events. PMID:25405093

  11. Normal activation of the supplementary motor area in patients with Parkinson's disease undergoing long-term treatment with levodopa.

    PubMed Central

    Rascol, O; Sabatini, U; Chollet, F; Fabre, N; Senard, J M; Montastruc, J L; Celsis, P; Marc-Vergnes, J P; Rascol, A

    1994-01-01

    Regional cerebral blood flow (rCBF) changes in cortical motor areas were measured during a movement of the dominant right hand in 15 patients with Parkinson's disease deprived of their usual levodopa treatment, in 11 patients with Parkinson's disease undergoing long-term treatment with levodopa, and in 15 normal volunteers. The supplementary motor areas were significantly activated in the normal subjects and in the patients receiving levodopa but not in the patients deprived of levodopa. The contralateral primary sensory motor area was significantly activated in all three groups. The ipsilateral primary sensory motor cortex was not activated in the normal subjects and the non-treated patients but was in the patients treated with levodopa. It is concluded that the supplementary motor area hypoactivation which is observed in akinetic non-treated patients with Parkinson's disease is not present in patients undergoing long-term treatment with levodopa. This result suggests that (a) levodopa improves the functional activity of supplementary motor areas in Parkinson's disease and (b) there is no pharmacological tolerance to this effect. The ipsilateral primary motor cortex activation observed in the patients treated with levodopa could be related to levodopa-induced abnormal involuntary movements. PMID:8201325

  12. Thyroid Function, Prevalent Coronary Heart Disease, and Severity of Coronary Atherosclerosis in Patients Undergoing Coronary Angiography

    PubMed Central

    Ling, Yan; Jiang, Jingjing; Gui, Minghui; Liu, Lin; Aleteng, Qiqige; Wu, Bingjie; Wang, Shanshan; Liu, Xiaojing; Gao, Xin

    2015-01-01

    This study investigated if free T4 and TSH concentrations or thyroid function categories were associated with prevalent CHD and the severity of coronary atherosclerosis in a population undergoing coronary angiography. This was a cross-sectional study including 1799 patients who were consecutively admitted and underwent coronary angiography. We evaluated the severity of coronary atherosclerosis using Gensini score. In the entire study population, free T4 level was inversely associated with prevalent CHD (OR = 0.95, 95% CI 0.91–0.99, P = 0.01) and the natural log-transformed Gensini score (ln(Gensini score)) (β = −0.03, 95% CI −0.05–−0.01, P = 0.005). The odds of CHD increased gradually across hyperthyroidism, subclinical hypothyroidism, and overt hypothyroidism groups using the euthyroid group as the reference, and the trend is borderline significant (P for trend = 0.051). When comparing to the euthyroid group, ln(Gensini score) of the overt hypothyroidism group was significantly higher (P = 0.009), but the trend was not significant (P for trend = 0.08). A significant association of thyroid function with CHD or ln(Gensini score) in euthyroid patients was not observed. The present study demonstrated an association of thyroid function with prevalent CHD and the severity of coronary atherosclerosis in a population undergoing coronary angiography. However, this association was not observed in euthyroid individuals. PMID:26770196

  13. Dipyridamole thallium imaging may not be a reliable screening test for coronary artery disease in patients undergoing vascular surgery

    SciTech Connect

    Marwick, T.H.; Underwood, D.A. )

    1990-01-01

    Dipyridamole thallium imaging has been proposed for cardiac risk stratification in patients undergoing peripheral vascular surgery. The purpose of this study was to define the benefit of this investigation in routine preoperative evaluation of these patients. The outcome of 86 patients undergoing vascular surgery procedures was examined in light of preoperative clinical assessment and dipyridamole SPECT thallium imaging (DST). Fifty-one patients (59%) were considered at high risk on clinical grounds, and 22 patients (26%) had perfusion defects. Ten patients suffered a perioperative coronary event, including unstable angina, myocardial infarction, or cardiac death. Seven of the patients with such events were among the 51 clinically high-risk subjects (14%). Three perioperative events occurred in the group of 19 patients with positive DST images who underwent surgery (16%), but the DST test failed to identify 7 patients who suffered coronary events. The frequency of abnormal thallium imaging was similar to the prevalence of angiographically significant coronary disease reported previously at this center, but considerably less than the rate of abnormal thallium imaging in past studies of vascular surgery patients. The application of the test to a low to moderate risk population is probably responsible for its lower predictive accuracy for coronary events. DST is not an ideal routine noninvasive technique for risk stratification in patients undergoing vascular surgery.

  14. Triple versus dual antiplatelet therapy for coronary heart disease patients undergoing percutaneous coronary intervention: A meta-analysis.

    PubMed

    Zhou, Hong; Feng, Xiao-Ling; Zhang, Hong-Ying; Xu, Fei-Fei; Zhu, Jie

    2013-10-01

    Coronary heart disease (CHD) is the leading cause of mortality worldwide. Previous studies have suggested that cilostazol-based triple antiplatelet therapy (TAT) may be more effective than conventional dual antiplatelet therapy (DAT) at improving the clinical outcomes of patients with CHD undergoing percutaneous coronary intervention (PCI). However, individually published results are inconclusive. The present meta-analysis evaluated controlled clinical studies to compare the clinical outcomes between TAT and DAT in patients with CHD undergoing PCI. Ten controlled clinical studies were included, with a total of 7,670 patients with CHD undergoing PCI. The total number included 3,925 patients treated with DAT (aspirin and clopidogrel) and 3745 patients treated with TAT (addition of cilostazol to DAT). The crude odds ratio (OR) with a 95% confidence interval (CI) was calculated with either the fixed or random effects model. The meta-analysis results indicated that patients in the TAT group had a significantly lower rate of restenosis compared with that of the DAT group (OR=0.59, 95% CI: 0.45-0.77; P<0.001). The rate of major adverse cardiac events (MACE) and target lesion revascularization (TLR) in the TAT group were significantly lower compared with those in the DAT group (MACE: OR=0.69, 95% CI: 0.56-0.85, P<0.001; TLR: OR=0.61, 95% CI: 0.43-0.88, P=0.008). However, no significant differences between the TAT and DAT groups in terms of mortality rate, myocardial infarction, target vessel revascularization and stent thrombosis were observed. In conclusion, the results of the present meta-analysis indicated that the efficacy and safety of cilostazol-based TAT therapy is greater than that of conventional DAT therapy for patients with CHD undergoing PCI. PMID:24137311

  15. Stereotactic body radiotherapy for chronic obstructive pulmonary disease patients undergoing or eligible for long-term domiciliary oxygen therapy

    PubMed Central

    Hara, Yu; Takeda, Atsuya; Eriguchi, Takahisa; Sanuki, Naoko; Aoki, Yousuke; Nishimura, Shuichi; Enomoto, Tatsuji; Shinkai, Masaharu; Kawana, Akihiko; Kaneko, Takeshi

    2016-01-01

    A major cause of death in patients undergoing long-term domiciliary oxygen therapy (LTOT) is lung cancer progression. In our institution, we actively perform stereotactic body radiotherapy (SBRT) on patients with early-stage non–small-cell lung cancer undergoing LTOT. In this study, we retrospectively analyzed the treatment efficacy and safety of SBRT for patients with T1-3N0M0 non–small-cell lung cancer who had been prescribed LTOT for treatment of chronic obstructive pulmonary disease (COPD). A total of 24 patients were studied. Their median age was 74 years (range, 63–87 years). The median duration from the start of LTOT to SBRT was 23 months (range, 0–85 months). Four of the 24 patients underwent lobectomy due to lung cancer. The median follow-up duration was 29 months (range, 5–79 months). One patient had a local recurrence. The median survival time was 30 months. The 3-year overall survival was 49%. In 6 of the 24 patients (25%), COPD presented with interstitial pneumonia. The 3-year overall survival for patients with COPD without interstitial pneumonia was significantly better than that for patients with both COPD and interstitial pneumonia (67% and 0%, respectively; P < 0.0001). Grade 5 radiation pneumonitis occurred in one patient (4%) with COPD with interstitial pneumonia. SBRT was tolerated by patients with early-stage non–small-cell lung cancer undergoing LTOT. SBRT should be considered for patients undergoing LTOT. However, clinicians should consider the risk of severe radiation pneumonitis in patients with interstitial pneumonia. PMID:26487713

  16. A disease risk index for patients undergoing allogeneic stem cell transplantation

    PubMed Central

    Gibson, Christopher J.; Cutler, Corey; Ho, Vincent T.; Koreth, John; Alyea, Edwin P.; Ritz, Jerome; Sorror, Mohamed L.; Lee, Stephanie J.; Deeg, H. Joachim; Storer, Barry E.; Appelbaum, Frederick R.; Antin, Joseph H.; Soiffer, Robert J.; Kim, Haesook T.

    2012-01-01

    The outcome of allogeneic HSCT varies considerably by the disease and remission status at the time of transplantation. Any retrospective or prospective HSCT study that enrolls patients across disease types must account for this heterogeneity; yet, current methods are neither standardized nor validated. We conducted a retrospective study of 1539 patients who underwent transplantation at Dana-Farber Cancer Institute/Brigham and Women's Hospital from 2000 to 2009. Using multivariable models for overall survival, we created a disease risk index. This tool uses readily available information about disease and disease status to categorize patients into 4 risk groups with significantly different overall survival and progression-free survival on the basis of primarily differences in the relapse risk. This scheme applies regardless of conditioning intensity, is independent of comorbidity index, and was validated in an independent cohort of 672 patients from the Fred Hutchinson Cancer Research Center. This simple and validated scheme could be used to risk-stratify patients in both retrospective and prospective HSCT studies, to calibrate HSCT outcomes across studies and centers, and to promote the design of HSCT clinical trials that enroll patients across diseases and disease states, increasing our ability to study nondisease-specific outcomes in HSCT. PMID:22709687

  17. Anesthetic considerations in the patients of chronic obstructive pulmonary disease undergoing laparoscopic surgeries.

    PubMed

    Khetarpal, Ranjana; Bali, Kusum; Chatrath, Veena; Bansal, Divya

    2016-01-01

    The aim of this study was to review the various anesthetic options which can be considered for laparoscopic surgeries in the patients with the chronic obstructive pulmonary disease. The literature search was performed in the Google, PubMed, and Medscape using key words "analgesia, anesthesia, general, laparoscopy, lung diseases, obstructive." More than thirty-five free full articles and books published from the year 1994 to 2014 were retrieved and studied. Retrospective data observed from various studies and case reports showed regional anesthesia (RA) to be valid and safer option in the patients who are not good candidates of general anesthesia like patients having obstructive pulmonary diseases. It showed better postoperative patient outcome with respect to safety, efficacy, postoperative pulmonary complications, and analgesia. So depending upon disease severity RA in various forms such as spinal anesthesia, paravertebral block, continuous epidural anesthesia, combined spinal epidural anesthesia (CSEA), and CSEA with bi-level positive airway pressure should be considered. PMID:26957682

  18. Anesthetic issues and perioperative blood pressure management in patients who have cerebrovascular diseases undergoing surgical procedures.

    PubMed

    Jellish, W Scott

    2006-11-01

    Patients who have cerebrovascular disease and vascular insufficiency routinely have neurosurgical and nonneurosurgical procedures. Anesthetic priorities must provide a still bloodless operative field while maintaining cardiovascular stability and renal function. Patients who have symptoms or a history of cerebrovascular disease are at increased risk for stroke, cerebral hypoperfusion, and cerebral anoxia. Type of surgery and cardiovascular status are key concerns when considering neuroprotective strategies. Optimization of current condition is important for a good outcome; risks must be weighed against perceived benefits in protecting neurons. Anesthetic use and physiologic manipulations can reduce neurologic injury and assure safe and effective surgical care when cerebral hypoperfusion is a real and significant risk. PMID:16935193

  19. Anesthetic considerations in the patients of chronic obstructive pulmonary disease undergoing laparoscopic surgeries

    PubMed Central

    Khetarpal, Ranjana; Bali, Kusum; Chatrath, Veena; Bansal, Divya

    2016-01-01

    The aim of this study was to review the various anesthetic options which can be considered for laparoscopic surgeries in the patients with the chronic obstructive pulmonary disease. The literature search was performed in the Google, PubMed, and Medscape using key words “analgesia, anesthesia, general, laparoscopy, lung diseases, obstructive.” More than thirty-five free full articles and books published from the year 1994 to 2014 were retrieved and studied. Retrospective data observed from various studies and case reports showed regional anesthesia (RA) to be valid and safer option in the patients who are not good candidates of general anesthesia like patients having obstructive pulmonary diseases. It showed better postoperative patient outcome with respect to safety, efficacy, postoperative pulmonary complications, and analgesia. So depending upon disease severity RA in various forms such as spinal anesthesia, paravertebral block, continuous epidural anesthesia, combined spinal epidural anesthesia (CSEA), and CSEA with bi-level positive airway pressure should be considered. PMID:26957682

  20. Filtration of Macrophage Migration Inhibitory Factor (MIF) in Patients with End Stage Renal Disease Undergoing Hemodialysis

    PubMed Central

    Pohl, Julia; Heisler, Martin; Totzeck, Matthias; Kleophas, Werner; Hetzel, Gerd R.; Kelm, Malte; Hendgen-Cotta, Ulrike; Rassaf, Tienush

    2015-01-01

    Background End stage renal disease (ESRD) patients are characterized by increased morbidity and mortality due to highest prevalence of cardiovascular disease. Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine that controls cellular signaling in human physiology, pathophysiology, and diseases. Increased MIF plasma levels promote vascular inflammation and development of atherosclerosis. We have shown that MIF is associated with vascular dysfunction in ESRD patients. Whether hemodialysis (HD) affects circulating MIF plasma levels is unknown. We here aimed to investigate whether HD influences the circulating MIF pool in ESRD patients. Methods and Results An observational single-center study was conducted. MIF plasma levels in ESRD patients were assessed before, during, and after a HD session (n = 29). Healthy age-matched volunteers served as controls to compare correlations of MIF plasma levels with inflammatory plasma components (n = 20). MIF removed from the circulating blood pool could be detected in the dialysate and allowed for calculation of totally removed MIF (MIF content in dialysate 219±4 μg/HD-session). MIF plasma levels were markedly decreased 2 hour after initiation of HD (MIF plasma level pre-HD 84.8±6 ng/ml to intra-HD 61.2±5 ng/ml p<0.001) and were replenished already 20 min after termination of HD to basal levels (intra-HD 61.2±5 ng/ml to post-HD 79.8±5 ng/ml, p<0.001). Conclusion MIF is a dialyzable plasma component that is effectively filtrated during HD from the patient blood pool in large amounts. After removal of remarkable amounts of MIF during a single HD session, MIF plasma pool is early reconstituted after termination of HD from unknown sources. PMID:26485680

  1. Evidence of residual disease in ossicles of patients undergoing cholesteatoma removal.

    PubMed

    Dornhoffer, J L; Colvin, G B; North, P

    1999-01-01

    For the past several years there has been much debate regarding the advisability of reusing the incus for ossicular reconstruction in cases involving cholesteatoma. There appears to be some evidence that microscopic foci of cholesteatoma in the incus could lead to reimplantation of the cholesteatoma should the incus be used in the reconstruction phase. In an effort to elucidate the incidence of microscopic residual cholesteatoma, the incudes of patients with cholesteatoma were examined both grossly in the operating room and microscopically in the laboratory for erosion and residual cholesteatoma. Our examination showed that a number of specimens apparently free of cholesteatoma after macroscopic examination had microscopic evidence of cholesteatoma. Likewise, microscopic examination of an incus that appeared to be free of residual cholesteatoma revealed epithelial cells deeply invading the bone. Macroscopic examination consistently underestimated the amount of erosion that was clearly evident upon histologic examination. In light of these findings, gross examination of the incus after removal of cholesteatoma is not reliably predictive of invasive microscopic disease. Reusing the ossicles in this situation creates the potential of reimplanting the disease. PMID:10219392

  2. [Prophylaxis against respiratory viral disease in pediatric and adult patients undergoing solid organ and hematopoietic stem cells transplantation].

    PubMed

    Álvarez, Ana M; Catalán, Paula; Alba, Andrea; Zubleta, Marcela

    2012-09-01

    Respiratory viruses have been identified as a cause of morbidity and mortality in patients undergoing SOT and HSCT, specially in children. The most frequent are respiratory syncytial virus (RSV), influenza (FLU), parainfluenza (PI) and adenovirus (ADV). These infections are associated with progression to severe lower respiratory tract infections in up to 60% of the cases. It is advised to apply universal protection recommendations for respiratory viruses (A2) and some specific measures for FLU and AD. FLU: Annual anti-influenza vaccination (from 4-6 months post-transplantation in SOT, 6 months in HSCT (A2)); post- exposure prophylaxis in FLU (oseltamivir for 10 days (B2)). In lung transplantion, the prophylaxis should last as long as the risk period (B2). ADV: There is no vaccine nor valid chemoprophylaxis strategy to prevent ADV disease. In some specific HSCT recipients, weekly PCR monitoring is recommended until day+100 (A3). PMID:23282554

  3. Short- and Long-term Outcomes in Patients with Connective Tissue Diseases Undergoing Percutaneous Coronary Intervention

    PubMed Central

    Zhou, Li; Chen, Hui; Li, Wei-Ping; Gao, Hong-Li; Li, Dong-Bao; Zhao, Hui-Qiang; Yao, Dao-Kuo; Li, Hong-Wei

    2016-01-01

    Background: Coronary artery disease (CAD) is a leading cause of morbidity and mortality in patients with connective tissue diseases (CTDs). Risk factors and clinical characteristics in these patients are not equivalent to those in traditional CAD patients. The objective of this study was to report short- and long-term clinical outcomes in a consecutive series of patients with CTD who underwent percutaneous coronary intervention (PCI) with stent implantation. Methods: The study group comprised 106 consecutive patients with CTD who underwent PCI in Beijing Friendship Hospital between January 2009 and June 2012. Medical records were analyzed retrospectively including clinical basic material, coronary angiogram data, and the incidence of major adverse cardiac events (MACEs) during the short- and long-term (median 3 years) follow-up. Results: Ninety-two of the patients (86.8%) had one or more traditional CAD risk factors. Multivessel disease was present in more than 2/3 of patients (73.6%). The left anterior descending coronary artery was the most commonly affected vessel (65.1%). Five bare-metal stents and 202 drug-eluting stents were implanted. After a median follow-up period of 36 months, thirteen patients (12.3%) died from cardiac causes, the rate of stent thrombosis was 9.4%, and the rate of target vessel revascularization (TVR) was 14.2%. Multivariate analysis revealed that hypertension (hazard ratio [HR] = 3.07, 95% confidence interval [CI]: 1.30–7.24, P = 0.041), anterior myocardial infarction (HR = 2.77, 95% CI: 1.06–7.03, P = 0.04), longer duration of steroid treatment (HR = 3.60, 95% CI: 1.43–9.08, P = 0.032), and C-reactive protein level >10 mg/L (HR = 3.98, 95% CI: 1.19–12.56, P = 0.036) were independent predictors of MACEs. Conclusions: Patients with CTD and CAD may have severe coronary lesions. PCI in these patients tends to result in an increased rate of stent thrombosis and TVR during long-term follow-up, which may be influenced by traditional

  4. Long-Term Outcomes and Causes of Death in Patients With Renovascular Disease Undergoing Renal Artery Stenting.

    PubMed

    Wallace, Eric L; Tasan, Ediz; Cook, Bryon S; Charnigo, Richard; Abdel-Latif, Ahmed K; Ziada, Khaled M

    2016-08-01

    Renovascular disease (RVD) can lead to hypertension and chronic kidney disease (CKD). Patients with advanced peripheral arterial disease (PAD) have a 5-year mortality of ∼30%. Rate and causes of death in patients with significant RVD, who share similar risk factors with patients having PAD, are not well defined. We assessed consecutive patients with RVD who underwent renal artery stenting at our institution over 6 years. Specific causes of death were ascertained, and the probability of survival was estimated. Cox models were fit to identify predictors of outcomes. We identified 281 patients with RVD who underwent renal stenting. Follow-up was available for all patients (median 5.1 years). All-cause mortality was 24.2% at 5 years and 33.7% at 7 years (compounded annualized death rate: 5.5%). Of the 68 deaths, 36 (52.9%) were cardiovascular (13.2% acute myocardial infarction, 13.2% stroke, 11.8% sudden death, and 10.3% congestive heart failure) and 32 (47.1%) deaths had noncardiovascular causes. In patients with RVD undergoing stenting, cardiovascular events are the most common causes of death. Compared to patients with advanced PAD, RVD may have a lower 5-year mortality. PMID:26430136

  5. A systematic review of dental disease in patients undergoing cancer therapy

    PubMed Central

    Napeñas, Joel J.; Hodgson, Brian D.; Stokman, Monique A.; Mathers-Stauffer, Vickie; Elting, Linda S.; Spijkervet, Fred K. L.; Brennan, Michael T.

    2010-01-01

    Introduction This purpose of this systematic review was to evaluate the literature and update our current understanding of the impact of present cancer therapies on the dental apparatus (teeth and periodontium) since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies. Review method A systematic literature search was conducted with assistance from a research librarian in the databases MEDLINE/PubMed and EMBASE for articles published between 1 January 1990 and 31 December 2008. Each study was independently assessed by two reviewers. Taking into account predetermined quality measures, a weighted prevalence was calculated for the prevalence of dental caries, severe gingival disease, and dental infection. Data on DMFT/dmft, DMFS/dmfs, plaque, and gingival indexes were also gathered. The level of evidence, recommendation, and guideline (if possible) were given for published preventive and management strategies. Results Sixty-four published papers between 1990 and 2008 were reviewed. The weighted overall prevalence of dental caries was 28.1%. The overall DMFT for patients who were post-antineoplastic therapy was 9.19 (SD, 7.98; n = 457). The overall plaque index for patients who were post-antineoplastic therapy was 1.38 (SD, 0.25; n = 189). The GI for patients who were post-chemotherapy was 1.02 (SD, 0.15; n = 162). The weighted prevalence of dental infections/abscess during chemotherapy was reported in three studies and was 5.8%. Conclusions Patients who were post-radiotherapy had the highest DMFT. The use of fluoride products and chlorhexidine rinses are beneficial in patients who are post-radiotherapy. There continues to be lack of clinical studies on the extent and severity of dental disease that are associated with infectious complications during cancer therapy. PMID:20449756

  6. Prevalence and risk factors associated with peripheral artery disease in elderly patients undergoing peritoneal dialysis

    PubMed Central

    Kuang, Ding-Wei; Li, Chiu-Leong; Kuok, Un-I; Cheung, Kin; Lio, Weng-In; Xin, Jing

    2012-01-01

    Background Rapid growth of the elderly peritoneal dialysis (PD) population is posing a special challenge for renal teams. Peripheral artery disease (PAD) has been reported to be an independent predictor of cardiovascular and all-cause mortality in hemodialysis patients. However, the prevalence and associated risk factors for PAD in elderly PD patients have not yet been fully investigated. Methods A total of 69 elderly PD patients were included in the present study. PAD was defined as either an ankle-brachial index < 0.9 or a history of intermittent claudication, lower-limb amputation, foot ulcers, or gangrene. On enrollment, clinical and biochemical characteristics were collected. Results The overall prevalence of PAD was 31.9%. Compared with non-PAD patients, PAD patients were significantly older and more likely to be female and have longer PD duration and lower diastolic blood pressure (P < 0.001, = 0.002, 0.018, and 0.007, respectively). Serum albumin level (P < 0.001) and residual renal Kt/V value (P < 0.001) were significantly lower, but the serum C-reactive protein level (P = 0.005) was significantly higher, in PAD patients compared with non-PAD patients. Logistic regression analysis showed that serum albumin level (odds ratio = 1.485, P = 0.040) and residual renal Kt/V value (odds ratio = 1.725, P = 0.016) were independently associated with PAD. Conclusion A high prevalence of PAD appeared among elderly PD patients in Macao. Serum albumin level and residual renal Kt/V value were independently related to PAD. PMID:23112578

  7. Intestinal microsporidiosis: a hidden risk in rheumatic disease patients undergoing anti-tumor necrosis factor therapy combined with disease-modifying anti-rheumatic drugs?

    PubMed Central

    Aikawa, Nadia Emi; de Oliveira Twardowsky, Aline; de Carvalho, Jozélio Freire; Silva, Clovis A; Silva, Ivan Leonardo Avelino França e; de Medeiros Ribeiro, Ana Cristina; Saad, Carla Gonçalves Schain; Moraes, Julio César Bertacini; de Toledo, Roberto Acayaba; Bonfá, Eloísa

    2011-01-01

    OBJECTIVE: Immunosuppressed patients are at risk of microsporidiosis, and this parasitosis has an increased rate of dissemination in this population. Our objective was to evaluate the presence of microsporidiosis and other intestinal parasites in rheumatic disease patients undergoing anti-tumor necrosis factor/disease-modifying anti-rheumatic drug treatment. METHODS: Ninety-eight patients (47 with rheumatoid arthritis, 31 with ankylosing spondylitis and 11 with psoriatic arthritis) and 92 healthy control patients were enrolled in the study. Three stool samples and cultures were collected from each subject. RESULTS: The frequency of microsporidia was significantly higher in rheumatic disease patients than in control subjects (36 vs. 4%, respectively; p<0.0001), as well as in those with rheumatic diseases (32 vs. 4%, respectively; p<0.0001), ankylosing spondylitis (45 vs. 4%, respectively; p<0.0001) and psoriatic arthritis (40 vs. 4%, respectively; p<0.0001), despite a similar social-economic class distribution in both the patient and control groups (p = 0.1153). Of note, concomitant fecal leukocytes were observed in the majority of the microsporidia-positive patients (79.5%). Approximately 80% of the patients had gastrointestinal symptoms, such as diarrhea (26%), abdominal pain (31%) and weight loss (5%), although the frequencies of these symptoms were comparable in patients with and without this infection (p>0.05). Rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis disease activity parameters were comparable in both groups (p>0.05). The duration of anti-tumor necrosis factor/disease-modifying anti-rheumatic drugs and glucocorticoid use were also similar in both groups. CONCLUSION: We have documented that microsporidiosis with intestinal mucosa disruption is frequent in patients undergoing concomitant anti-tumor necrosis factor/disease-modifying anti-rheumatic drug therapy. Impaired host defenses due to the combination of the underlying disease

  8. Adiponectin and resistin in acute and chronic graft-vs-host disease patients undergoing allogeneic hematopoietic stem cell transplantation

    PubMed Central

    Robak, Oliver; Kuzmina, Zoya; Winkler, Andreas; Kalhs, Peter; Rabitsch, Werner; Greinix, Hildegard

    2016-01-01

    Aim To investigate the association of adiponectin and resistin levels in patients undergoing hematopoietic stem cell transplantation (HSCT) with the clinical outcome, including the occurrence of acute and chronic graft-vs-host disease (GVHD), non-relapse mortality, and overall survival. Methods We prospectively collected serum samples from 40 patients undergoing either autologous (n = 12; 10 male) or allogeneic (n = 28; 11 male) HSCT for up to 12 months post HSCT and determined adiponectin and resistin serum concentrations using enzyme-linked immunosorbent assay. Results There were no significant differences in adiponectin levels (18.5 vs 9.3 µg/mL, P = 0.071) and adiponectin/BMI ratio (0.82 vs 0.39, P = 0.068) between patients with acute GVHD grades 2-4 and autologous controls. However, resistin values were significantly lower in patients with acute GVHD grades 2-4 than in autologous controls (4.6 vs 7.3 ng/mL, P = 0.030). Adiponectin levels were higher in patients with chronic GVHD (n = 17) than in autologous controls (13.5 vs 7.6 µg/mL, P = 0.051), but the difference was not significant. Adiponectin/BMI ratio was significantly higher in patients with chronic GVHD than in autologous controls (0.59 vs 0.25, P = 0.006). Patients dying from relapse also had significantly lower adiponectin levels (8.2 µg/mL) and adiponectin/BMI ratio (0.3) on admission than surviving allogeneic (15.8 µg/mL, P = 0.030 and 0.7, P = 0.004) and surviving autologous patients (19.2 µg/mL, P = 0.031 and 0.7, P = 0.021). Conclusion Adiponectin and resistin levels were altered in patients with acute and chronic GVHD compared to autologous controls and were associated with overall survival and relapse mortality in patients undergoing allogeneic HSCT. PMID:27374827

  9. Coronary Stents in Patients with ST-Elevation Myocardial Infarction and Chronic Kidney Disease Undergoing Primary Percutaneous Coronary Intervention

    PubMed Central

    Ahmed, Khurshid; Chakraborty, Rabin; Ahmed, Sumera; Hong, Young Joon; Sim, Doo Sun; Park, Keun Ho; Kim, Ju Han; Ahn, Youngkeun; Kang, Jung Chaee; Cho, Myeong Chan; Kim, Chong Jin; Kim, Young Jo

    2012-01-01

    Background and Objectives Chronic kidney disease (CKD) is associated with poor outcomes after percutaneous coronary intervention (PCI). We sought to compare different coronary stents used during primary PCI in patients with ST-elevation myocardial infarction (STEMI) and CKD. Subjects and Methods We selected 2408 consecutive STEMI patients with CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2) undergoing primary PCI and divided them into 5 groups based on the type of stent implanted: 1) bare metal stent (BMS), 2) paclitaxel-eluting stent (PES), 3) sirolimus-eluting stent (SES), 4) zotarolimus-eluting stent (ZES), or 5) everolimus-eluting stent (EES). The study endpoint was the number of major adverse cardiac events (MACE) at 12 months. Results There was no significant difference in the incidence of 12-month myocardial infarction, target lesion revascularization, or target vessel revascularization between stent groups; however, the overall rate of repeat revascularization differed significantly between groups. All-cause death differed significantly among the groups. The incidence of 12-month MACE in BMS, PES, SES, ZES, and EES was 8.3%, 9.8%, 8.6%, 5.5%, and 2.6%, respectively (p<0.001). Kaplan-Meier analysis did not show a significant differences in 12-month MACE-free survival among the groups (log-rank p=0.076). This finding remained the same after adjusting for multiple confounders (p=0.147). Conclusion Any of the 5 stents can be used to treat STEMI patients with CKD undergoing primary PCI; all have similar risk of 12-month MACE. This result is hypothesis-generating and warrants further evaluation with a long-term randomized study. PMID:23323121

  10. 75 FR 58394 - Agency Forms Undergoing Paperwork Reduction Act Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-24

    ... protects infants against infections, chronic diseases like diabetes and obesity, and even childhood..., obesity, and poor health overall persistently have the lowest breastfeeding rates. Public...

  11. Validation of the Disease-Specific Components of the Kidney Disease Quality of Life-36 (KDQOL-36) in Chinese Patients Undergoing Maintenance Dialysis

    PubMed Central

    2016-01-01

    Aim The aim of this study was to evaluate the validity, reliability and sensitivity of the disease-specific items of the Kidney Disease Quality of Life-36 (KDQOL-36) in Chinese patients undergoing maintenance dialysis. Methods The content validity was assessed by content validity index (CVI) in ten subjects. 356 subjects were recruited for pilot psychometric testing. The internal construct validity was assessed by corrected item-subscale total correlation. Confirmatory factor analysis (CFA) was used to confirm the factor structure. The convergent validity was assessed by Pearson’s correlation test between the disease specific subscale scores and SF-12 version 2 Health Survey (SF-12 v2) scores. The reliability was assessed by the internal consistency (Cronbach’s Alpha coefficient) and 2-week test–retest reliability (intraclass correlation coefficient (ICC)). The sensitivity was determined by performing known group comparisons by independent t-test. Results The CVI on clarity and relevance was ≥ 0.9 for all items. Corrected item- total correlation scores were ≥0.4 for all, except an item related to problems with access site. CFA confirmed the 3-factor structure of the disease-specific component of the KDQOL-36. The correlation coefficients between the disease-specific domain scores and the SF-12 v2 physical and mental component summary scores ranged from 0.328 to 0.492. The reliability was good (Cronbach’s alpha coefficients ranged from 0.810 to 0.931, ICC ranged from 0.792 to 0.924). Only the effect subscale was sensitive in detecting differences in HRQOL between haemodialysis and peritoneal dialysis patients, with effect size = 0.68. Conclusion The disease-specific items of the KDQOL-36 are a valid, reliable and sensitive measure to assess the health-related quality of life of Chinese patients on maintenance dialysis. PMID:27148742

  12. Biochemical pathways of breath ammonia (NH3) generation in patients with end-stage renal disease undergoing hemodialysis.

    PubMed

    Chen, W; Laiho, S; Vaittinen, O; Halonen, L; Ortiz, F; Forsblom, C; Groop, P-H; Lehto, M; Metsälä, M

    2016-01-01

    Breath ammonia (NH3) has been proposed as a potential biomarker in monitoring hemodialysis (HD) adequacy, since a strong correlation between blood urea and mouth-exhaled breath NH3 has been observed in patients with end-stage renal disease (ESRD) undergoing HD. However, the biochemical pathways for breath NH3 generation from blood urea have not been demonstrated. In this study, we show a strong correlation (r s  =  0.77, p  <  0.001) between blood and salivary urea, indicating that salivary urea levels reflect blood urea levels. Salivary urea is in turn strongly correlated to salivary ammonia ([Formula: see text] + NH3) in most of the patients. This confirms that the hydrolysis of urea by urease generates ammonia in the oral cavity. A further strong correlation between salivary ammonia and breath NH3 indicates that salivary ammonia evaporates into gas phase and turns to breath NH3. Therefore, blood urea is a major biochemical source of breath NH3. Since breath NH3 is generated predominantly in the oral cavity, the levels of breath NH3 are influenced significantly by the patient's oral condition including urease activity and salivary pH. Our results agree with previous studies that have shown a connection between salivary urea and breath NH3. PMID:27516572

  13. Long-Term Follow-Up Evaluation of Renal Function in Patients with Chronic Kidney Disease Undergoing Cardiac Surgery

    PubMed Central

    Kamei, Felipe Kenji Oshiro; do Nascimento, Tarcísia Karoline; Abou Ismail, Anas; Herbas Palomo, Jurema da Silva; da Silva Magro, Marcia Cristina; Ferreira, Fátima Gil; de Oliveira, Larissa Bertacchini; Baldacin Rodrigues, Adriano Rogério; Galvão de Lima, José Jayme

    2016-01-01

    Background. Acute kidney injury (AKI) is a common complication of cardiac surgery but its long-term consequences, in patients with chronic kidney disease (CKD), are not known. Methods. We compared the long-term prognoses of CKD patients who developed (n = 23) and did not develop (n = 35) AKI during the period of hospitalization after undergoing coronary artery bypass graft (CABG). Fifty-eight patients who survived (69.6 ± 8.4 years old, 72% males, 83% Whites, 52% diabetics, baseline GFR: 46 ± 16 mL/min) were followed up for 47.8 ± 16.4 months and treated for secondary prevention of events. Results. There were 6 deaths, 4 in the AKI+ and 2 in the AKI− group (Log-rank = 0.218), two attributed to CV causes. At the end of the study, renal function was similar in the two groups. One AKI− patient was started on dialysis. Only 4 patients had an increase in serum creatinine ≥ 0.5 mg/dL during follow-up. Conclusion. CKD patients developing AKI that survived the early perioperative period of coronary intervention present good renal and nonrenal long-term prognosis, compared to patients who did not develop AKI.

  14. β-d-Glucan Screening for Detection of Invasive Fungal Disease in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

    PubMed Central

    Koltze, Antonia; Rath, Peter; Schöning, Stefan; Steinmann, Jörg; Wichelhaus, Thomas A.; Bader, Peter; Bochennek, Konrad

    2015-01-01

    While the assessment of β-d-glucan (BDG) levels in adults improves the early diagnosis of invasive fungal disease (IFD), data on BDG levels in children are limited. We therefore assessed in a prospective cohort study the value of serial BDG screening for early detection of IFD in children undergoing allogeneic hematopoietic stem cell transplantation (HSCT). IFD was defined according to the revised European Organization for Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSG) criteria, with the necessary modification that BDG was not included as a microbiological criterion. For the analysis, a total of 702 serum samples were obtained in 34 pediatric HSCT recipients. Proven IFD occurred in two patients (fusariosis and Candida sepsis, respectively), and probable invasive aspergillosis was diagnosed in four patients. Analyses including different cutoff values for BDG levels and different definitions of the onset of IFD demonstrated that the BDG assay has a relatively high sensitivity and good negative predictive value, whereas the positive predictive value has major limitations (<30%). Receiver operating characteristic analyses suggested an optimal cutoff between 60 and 70 pg/ml for different definitions of the onset of IFD. Our data show that BDG screening in pediatric HSCT recipients has a low positive predictive value and is therefore of limited usefulness. PMID:26041896

  15. Higher plasma bilirubin predicts veno-occlusive disease in early childhood undergoing hematopoietic stem cell transplantation with cyclosporine

    PubMed Central

    Kim, Kwi Suk; Moon, Aree; Kang, Hyoung Jin; Shin, Hee Young; Choi, Young Hee; Kim, Hyang Sook; Kim, Sang Geon

    2016-01-01

    AIM: To analyze the association between plasma bilirubin levels and veno-occlusive disease (VOD) in non-adult patients undergoing hematopoietic stem cell transplantation (HSCT) during cyclosporine therapy. METHODS: A total of 123 patients taking cyclosporine were evaluated using an electronic medical system at the Seoul National University Children’s Hospital from the years 2004 through 2011. Patients were grouped by age and analyzed for incidence and type of adverse drug reactions (ADRs) including VOD. RESULTS: The HSCT patients were divided into three age groups: G#1 ≥ 18; 9 ≤ G#2 ≤ 17; and G#3 ≤ 8 years of age). The majority of transplant donor types were cord blood transplantations. Most prevalent ADRs represented acute graft-vs-host disease (aGVHD) and VOD. Although the incidences of aGVHD did not vary among the groups, the higher frequency ratios of VOD in G#3 suggested that an age of 8 or younger is a risk factor for developing VOD in HSCT patients. After cyclosporine therapy, the trough plasma concentrations of cyclosporine were lower in G#3 than in G#1, indicative of its increased clearance. Moreover, in G#3 only, a maximal total bilirubin level (BILmax) of ≥ 1.4 mg/dL correlated with VOD incidence after cyclosporine therapy. CONCLUSION: HSCT patients 8 years of age or younger are more at risk for developing VOD, diagnosed as hyperbilirubinemia, tender hepatomegaly, and ascites/weight gain after cyclosporine therapy, which may be represented by a criterion of plasma BILmax being ≥ 1.4 mg/dL, suggestive of more sensitive VOD indication in this age group. PMID:27358786

  16. Incidence and Severity of Coronary Artery Disease in Patients with Atrial Fibrillation Undergoing First-Time Coronary Angiography

    PubMed Central

    Kralev, Stefan; Schneider, Kathrin; Lang, Siegfried; Süselbeck, Tim; Borggrefe, Martin

    2011-01-01

    Background In standard reference sources, the incidence of coronary artery disease (CAD) in patients with atrial fibrillation (AF) ranged between 24 and 46.5%. Since then, the incidence of cardiovascular risk factors (CRF) has increased and modern treatment strategies (“pill in the pocket”) are only applicable to patients without structural heart disease. The aim of this study was to investigate the incidence and severity of CAD in patients with AF. Methods From January 2005 until December 2009, we included 261 consecutive patients admitted to hospital with paroxysmal, persistent or permanent AF in this prospective study. All patients underwent coronary angiography and the Framingham risk score (FRS) was calculated. Patients with previously diagnosed or previously excluded CAD were excluded. Results The overall incidence of CAD in patients presenting with AF was 34%; in patients >70 years, the incidence of CAD was 41%. The incidence of patients undergoing a percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) was 21%. Patients with CAD were older (73±8 years vs 68±10 years, p = 0.001), had significantly more frequent hypercholesterolemia (60% vs 30%, p<0.001), were more frequent smokers (26% vs 13%, p = 0.017) and suffered from angina more often (37% vs 2%, p<0.001). There was a significant linear trend among the FRS categories in percentage and the prevalence of CAD and PCI/CABG (p<0.0001). Conclusions The overall incidence of CAD in patients presenting with AF was relatively high at 34%; the incidence of PCI/CABG was 21%. Based upon increasing CRF in the western world, we recommend a careful investigation respecting the FRS to either definitely exclude or establish an early diagnosis of CAD – which could contribute to an early and safe therapeutic strategy considering type Ic antiarrhythmics and oral anticoagulation. PMID:21957469

  17. Presentation, treatment, and outcome differences between men and women undergoing revascularization or amputation for lower extremity peripheral arterial disease

    PubMed Central

    Lo, Ruby C.; Bensley, Rodney P.; Dahlberg, Suzanne E.; Matyal, Robina; Hamdan, Allen D.; Wyers, Mark; Chaikof, Elliot L.; Schermerhorn, Marc L.

    2013-01-01

    Objective Prior studies have suggested treatment and outcome disparities between men and women for lower extremity peripheral arterial disease after surgical bypass. Given the recent shift toward endovascular therapy, which has increasingly been used to treat claudication, we sought to analyze sex disparities in presentation, revascularization, amputation, and inpatient mortality. Methods We identified individuals with intermittent claudication and critical limb ischemia (CLI) using International Classification of Diseases, Ninth Revision codes in the Nationwide Inpatient Sample from 1998 to 2009. We compared presentation at time of intervention (intermittent claudication vs CLI), procedure (open surgery vs percutaneous transluminal angioplasty or stenting vs major amputation), and in-hospital mortality for men and women. Regional and ambulatory trends were evaluated by performing a separate analysis of the State Inpatient and Ambulatory Surgery Databases from four geographically diverse states: California, Florida, Maryland, and New Jersey. Results From the Nationwide Inpatient Sample, we identified 1,797,885 patients (56% male) with intermittent claudication (26%) and CLI (74%), who underwent 1,865,999 procedures (41% open surgery, 20% percutaneous transluminal angioplasty or stenting, and 24% amputation). Women were older at the time of intervention by 3.5 years on average and more likely to present with CLI (75.9% vs 72.3%; odds ratio [OR], 1.21; 95% confidence interval [CI], 1.21–1.23; P < .01). Women were more likely to undergo endovascular procedures for both intermittent claudication (47% vs 41%; OR, 1.27; 95% CI, 1.25–1.28; P < .01) and CLI (21% vs 19%; OR, 1.14; 95% CI, 1.13–1.15; P < .01). From 1998 to 2009, major amputations declined from 18 to 11 per 100,000 in men and 16 to 7 per 100,000 in women, predating an increase in total CLI revascularization procedures that was seen starting in 2005 for both men and women. In-hospital mortality was

  18. Effects of dexmedetomidine on oxygenation and lung mechanics in patients with moderate chronic obstructive pulmonary disease undergoing lung cancer surgery

    PubMed Central

    Lee, Su Hyun; Kim, Namo; Lee, Chang Yeong; Ban, Min Gi; Oh, Young Jun

    2016-01-01

    BACKGROUND Chronic obstructive pulmonary disease (COPD) is a risk factor that increases the incidence of postoperative cardiopulmonary morbidity and mortality after lung resection. Dexmedetomidine, a selective α2-adrenoreceptor agonist, has been reported previously to attenuate intrapulmonary shunt during one-lung ventilation (OLV) and to alleviate bronchoconstriction. OBJECTIVE The objective is to determine whether dexmedetomidine improves oxygenation and lung mechanics in patients with moderate COPD during lung cancer surgery. DESIGN A randomised, double-blinded, placebo-controlled study. SETTING Single university hospital. PARTICIPANTS Fifty patients scheduled for video-assisted thoracoscopic surgery who had moderate COPD. Patients were randomly allocated to a control group or a Dex group (n = 25 each). INTERVENTIONS In the Dex group, dexmedetomidine was given as an initial loading dose of 1.0 μg kg−1 over 10 min followed by a maintenance dose of 0.5 μg kg−1 h−1 during OLV while the control group was administered a comparable volume of 0.9% saline. Data were measured at 30 min (DEX-30) and 60 min (DEX-60) after dexmedetomidine or saline administration during OLV. MAIN OUTCOME MEASURES The primary outcome was the effect of dexmedetomidine on oxygenation. The secondary outcome was the effect of dexmedetomidine administration on postoperative pulmonary complications. RESULTS Patients in the Dex group had a significantly higher PaO2/FiO2 ratio (27.9 ± 5.8 vs. 22.5 ± 8.4 and 28.6 ± 5.9 vs. 21.0 ± 9.9 kPa, P < 0.05), significantly lower dead space ventilation (19.2 ± 8.5 vs. 24.1 ± 8.1 and 19.6 ± 6.7 vs. 25.3 ± 7.8%, P < 0.05) and higher dynamic compliance at DEX-30 and DEX-60 (P = 0.0001 and P = 0.0184) compared with the control group. In the Dex group, the PaO2/FiO2 ratio in the postoperative period was significantly higher (P = 0.022) and the incidence of ICU admission was

  19. The Impact of the Availability of Prevention Studies on the Desire to Undergo Predictive Testing in Persons at-risk for Autosomal Dominant Alzheimer’s Disease

    PubMed Central

    Hooper, Megan; Grill, Joshua D.; Rodriguez-Agudelo, Yaneth; Medina, Luis D.; Fox, Michelle; Alvarez-Retuerto, Ana Isabel; Wharton, David; Brook, Jenny; Ringman, John M.

    2013-01-01

    Persons at-risk for autosomal dominant neurodegenerative diseases provide the opportunity to efficiently test preventive interventions. Only a minority of such persons, however, choose to undergo revealing genetic testing, presenting a challenge to enrollment. Thirty-four preclinical Latinos (n = 26) and non-Latinos at-risk for familial Alzheimer’s disease (FAD) unaware of their genetic status were administered a questionnaire exploring their interest in undergoing revealing genetic testing at baseline and in the context of eligibility for four prevention trials of increasing invasiveness. Forty-four percent of subjects expressed a baseline interest in undergoing revealing testing which increased to 85% in order to be eligible for a study of an oral drug "felt to be very safe.” If there were a 50% chance of receiving placebo, this number dropped to 62% (p = 0.02). For those not interested in a study involving a 50% chance of receiving placebo, a range of 5% to 40% chance of receiving placebo was given as acceptable. For more invasive studies, living in the U.S. (as opposed to Mexico) positively influenced the likelihood of participating. Our data suggests that clinical trial designs in which persons must confront their genetic status prior to enrollment are feasible. Study designs to minimize the likelihood of being placed on placebo or provide the eventual administration of the drug through open-label extensions should be considered. PMID:23876673

  20. Effect of Perioperative β-Blockers on Pulmonary Complications among Patients with Chronic Obstructive Pulmonary Disease Undergoing Lung Resection Surgery

    PubMed Central

    Kamath, A.; Stover, D. E.; Hemdan, A.; Belinskaya, I.; Steingart, R. M.; Taur, Y.; Feinstein, M. B.

    2015-01-01

    The aim of this study is to determine if COPD patients undergoing lung resection with perioperative β-blocker use are more likely to suffer postoperative COPD exacerbations than those that did not receive perioperative β-blockers. Methods. A historical cohort study of COPD patients, undergoing lung resection surgery at Memorial Sloan-Kettering Cancer Center between 2002 and 2006. Primary outcomes were the rate of postoperative COPD exacerbations, defined as any initiation or increase of glucocorticoids for documented bronchospasm. Results. 520 patients with COPD were identified who underwent lung resection. Of these, 205 (39%) received perioperative β-blockers and 315 (61%) did not. COPD was mild among 361 patients (69% of all patients), moderate in 117 patients (23%), and severe in 42 patients (8%). COPD exacerbations occurred among 11 (5.4%) patients who received perioperative β-blockers and among 20 (6.3%) patients who did not. Secondary outcomes, which included respiratory failure, 30-day mortality, and the presence or absence of any cardiovascular complication, ICU transfer, cardiovascular complication, or readmission within 30 days, did not differ in prevalence between the two groups. Conclusions. This study implies that perioperative β-blockers use among COPD patients undergoing lung resection surgery does not impact the rate of exacerbations. PMID:26421192

  1. Prevalence of carotid artery stenosis in neurologically asymptomatic patients undergoing coronary artery bypass grafting for coronary artery disease: Role of anesthesiologist in preoperative assessment and intraoperative management

    PubMed Central

    Taneja, Sameer; Chauhan, Sandeep; Kapoor, Poonam Malhotra; Jagia, Priya; Bisoi, A. K.

    2016-01-01

    Objective(s): This study aimed to determine the prevalence of carotid artery stenosis (CAS) due to atherosclerosis in neurologically asymptomatic patients undergoing coronary artery bypass grafting (CABG) for coronary artery disease (CAD). It contemplated a greater role for the cardiac anesthesiologist in the perioperative management of such patients with either previously undiagnosed carotid artery disease or towards re-assessment of severity of CAS. Design: Prospective, observational clinical study. Setting: Operation room of a cardiac surgery centre of a tertiary teaching hospital. Participants: A hundred adult patients with New York Heart Association (NYHA) classification I to III presenting electively for CABG. Interventions: All patients included in this study were subjected to ultrasonic examination by means of acarotid doppler scan to access for presence of CAS just prior to induction of general anesthesia. Measurements and Main Results: Based on parameters measured using carotid doppler, the presence of CAS was defined using standard criteria. The prevalence of CAS was found to be as high as 38% amongst the patients included in our study. The risk factors for CAS were identified to be advanced age, history of smoking, diabetes mellitus, dyslipidaemia and presence of a carotid bruit. Conclusion: This study points towards the relatively wide prevalence of carotid artery disease in neurologically asymptomatic patients undergoing CABG for CAD in the elective setting. It highlights the need to routinely incorporate carotid ultrasonography in the armamentarium of the cardiac anesthesiologist as standard of care for all patients presenting for CABG. PMID:26750678

  2. The use of desmopressin in the management of two patients with von Willebrand's disease undergoing periodontal surgery. 2 case reports.

    PubMed

    Petrover, M G; Cohen, C I

    1990-04-01

    Von Willebrand's disease is a genetic bleeding disorder characterized by either a reduced plasma concentration of von Willebrand's factor (vWF) or a qualitative deficiency in that vWF which is produced. Previous therapy consisted of injecting concentrates of vWF manufactured from the pooled plasma of multiple donors. With the increased incidence and risk of serum borne transmission of such diseases as hepatitis and AIDS, the advantages of an alternative mode of therapy was obvious. In the course of using 1-desamino-8-D-arginine (desmopressin or DDAVP, a synthetic analogue of 8-arginine vasopressin, a hormone secreted in the posterior pituitary gland) in the treatment of diabetes insipidus, it was discovered that this drug causes the release of bound vWF into the plasma. The elevation lasts for several hours and is effective in producing hemostasis in some types of mild to moderate von Willebrand's disease. In 1984, desmopressin was approved for this usage in the United States. This paper discusses the use of DDAVP in the management of von Willebrand's disease and present two case reports of patients with von Willebrand's disease and in need of periodontal surgery. PMID:2324924

  3. Cardiovascular complications in patients with megaesophagus due to Chagas disease undergoing the Serra-Dória operation.

    PubMed

    Júnior, Eumildo de Campos; Cardinalli-Neto, Augusto; Albaneze Borim, Aldenis; Bestetti, Reinaldo B

    2012-05-01

    The Serra-Dória procedure has been used in the treatment of advanced or relapsed megaesophagus due to Chagas disease. Little is known, however, about cardiovascular complications following this procedure. The purpose of this study was to settle independent predictors of cardiovascular complications following the Serra-Dória procedure in patients with megaesophagus secondary to chronic Chagas disease. A total of 76 patients who underwent the Serra-Dória operation for Chagas disease megaesophagus from 1998 to 2010 were included. A multivariate stepwise logistic regression analysis was performed to identify predictors of cardiovascular complications. Mean age was 61±10 years; 55% were male. Advanced megaesophagus (grades III/IV) were found in 65 (86%) of patients. Twenty-two (29%) patients had one comorbidity, and five (7%) three co-morbidities before operation. Two (3%) patients died following the operation. Twenty-nine (38%) patients presented cardiovascular complication following the Serra-Dória procedure; 15 (44%) were mild, 7 (21%) moderate, and 12 (35%) severe. Age>61 years was the only independent predictor of cardiovascular complication following Serra-Dória procedure. In patients with megaesophagus secondary to chronic Chagas disease, the Serra-Dória procedure is associated with a low mortality rate and a high frequency of cardiac complication. PMID:22322246

  4. Risk of Stroke in Patients with Stable Coronary Artery Disease Undergoing Percutaneous Coronary Intervention versus Optimal Medical Therapy: Systematic Review and Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Taglieri, Nevio; Bacchi Reggiani, Maria Letizia; Ghetti, Gabriele; Saia, Francesco; Dall’Ara, Gianni; Gallo, Pamela; Moretti, Carolina; Palmerini, Tullio; Marrozzini, Cinzia; Marzocchi, Antonio; Rapezzi, Claudio

    2016-01-01

    Background Stroke is a rare but serious adverse event associated with percutaneous coronary intervention (PCI). However, the relative risk of stroke between stable patients undergoing a direct PCI strategy and those undergoing an initial optimal medical therapy (OMT) strategy has not been established yet. This study sought to investigate if, in patients with stable coronary artery disease (SCAD), an initial strategy PCI is associated with a higher risk of stroke than a strategy based on OMT alone. Methods We performed a meta-analysis of 6 contemporary randomized control trials in which 5673 patients with SCAD were randomized to initial PCI or OMT. Only trials with stent utilization more than 50% were included. Study endpoint was the rate of stroke during follow up. Results Mean age of patients ranged from 60 to 65 years and stent utilization ranged from 72% to 100%. Rate of stroke was 2.0% at a weighted mean follow up of 55.3 months. On pooled analysis, the risk of stroke was similar between patients undergoing a PCI plus OMT and those receiving only OMT (2.2% vs. 1.8%, OR on fixed effect = 1.24 95%CI: 0.85–1.79). There was no heterogeneity among the studies (I2 = 0.0%, P = 0.15). On sensitivity analysis after removing each individual study the pooled effect estimate remains unchanged. Conclusions In patients with SCAD an initial strategy based on a direct PCI is not associated with an increased risk of stroke during long-term follow up compared to an initial strategy based on OMT alone. PMID:27391212

  5. Importance of Extracranial Disease Status and Tumor Subtype for Patients Undergoing Radiosurgery for Breast Cancer Brain Metastases

    SciTech Connect

    Dyer, Michael A.; Kelly, Paul J.; Chen, Yu-Hui; Pinnell, Nancy E.; Lee, Eudocia Q.; Arvold, Nils D.; Lin, Nancy U.

    2012-07-15

    Purpose: In this retrospective study, we report on outcomes and prognostic factors for patients treated with stereotactic radiosurgery (SRS) for breast cancer brain metastases. Methods and Materials: We identified 132 consecutive patients with breast cancer who were treated with SRS for brain metastases from January 2000 through June 2010. We retrospectively reviewed records of the 51 patients with adequate follow-up data who received SRS as part of the initial management of their brain metastases. Overall survival (OS) and time to central nervous system (CNS) progression from the date of SRS were calculated using the Kaplan-Meier method. Prognostic factors were evaluated using the Cox proportional hazards model. Results: Triple negative subtype was associated with CNS progression on univariate analysis (hazard ratio [HR] = 5.0, p = 0.008). On multivariate analysis, triple negative subtype (HR = 8.6, p = 0.001), Luminal B subtype (HR = 4.3, p = 0.03), and omission of whole-brain radiation therapy (HR = 3.7, p = 0.02) were associated with CNS progression. With respect to OS, Karnofsky Performance Status (KPS) {<=} 80% (HR = 2.0, p = 0.04) and progressive extracranial disease (HR = 3.1, p = 0.002) were significant on univariate analysis; KPS {<=} 80% (HR = 4.1, p = 0.0004), progressive extracranial disease (HR = 6.4, p < 0.0001), and triple negative subtype (HR = 2.9, p = 0.04) were significant on multivariate analysis. Although median survival times were consistent with those predicted by the breast cancer-specific Graded Prognostic Assessment (Breast-GPA) score, the addition of extracranial disease status further separated patient outcomes. Conclusions: Tumor subtype is associated with risk of CNS progression after SRS for breast cancer brain metastases. In addition to tumor subtype and KPS, which are incorporated into the Breast-GPA, progressive extracranial disease may be an important prognostic factor for OS.

  6. Observational clinical study of 22 adult-onset Pompe disease patients undergoing enzyme replacement therapy over 5years.

    PubMed

    Stepien, Karolina M; Hendriksz, Christian J; Roberts, Mark; Sharma, Reena

    2016-04-01

    Pompe disease is an autosomal recessive disease resulting from deficiency of the acid alpha-glucosidase (GAA). The late-onset Pompe Disease (LOPD) patients develop muscular and respiratory complications later in life. We describe a retrospective observational cohort study including 22 patients with LOPD. The cohort was assessed at baseline before Enzyme Replacement Therapy (ERT) with alglucosidase alpha (20mg/kg biweekly) was commenced and subsequently relevant information was collected at 2, 4 and 5years later. The median age of the patients at study entry was 44years (16-64years), with median disease duration of 11.5years (4-31years). At baseline, 10 patients (45%) could walk without support, 12 (55%) could walk with unilateral or bilateral support including 3/12 were wheelchair bound. Mean predicted FVC % was 55.7 (95% CI 45-66) of predicted normal at baseline and showed no significant change after 5years (54.6 (95% CI 43-66)), (all p=0.9815). Mean FVC % supine was 41.8 (95% CI 33.8-49) of predicted normal at baseline and remained significantly unchanged at 5years (48.4 (95% CI 37-59.6)), (all p=0.8680). The overnight non-invasive ventilator dependence increased by 18.2% as compared with baseline and requirement of mobility aids increased during this period by 5.2% as compared with the baseline. Mean walking distance at 6min walk test was 411.5 (95% CI 338-485) at baseline, 266.5 (95% CI 187-346) m at 2years, 238.6 (95% CI 162-315) m at 4years and 286.8 (95% CI 203-370) m at 5years (p=0.1981; ANOVA was completed only for 14 patients). A gradual decline in FVC% predicted was noted only in four cases and a decline in FVC% supine in two other. Only one patient showed a decline in both pulmonary function tests. In all remaining cases (17/22) respiratory function remains stable. In conclusion overall pulmonary function tests and mobility remained stable for 5years in majority of patients on ERT. However, in some patients they continued to decline in spite of ERT

  7. Thallium stress testing does not predict cardiovascular risk in diabetic patients with end-stage renal disease undergoing cadaveric renal transplantation

    SciTech Connect

    Holley, J.L.; Fenton, R.A.; Arthur, R.S. )

    1991-05-01

    This study assessed the usefulness of thallium stress testing as a predictor of perioperative cardiovascular risk in diabetic patients with end-stage renal disease undergoing cadaveric renal transplantation. Demographic factors influencing the exercise performance in these patients were also examined. The medical records of 189 consecutive patients with diabetic nephropathy who were evaluated for cadaveric renal transplantation were reviewed. Thallium stress testing was the initial examination of cardiovascular status in 141 patients. An adequate examination was one in which at least 70% of maximum heart rate was achieved. A thallium stress test was normal if there were no ST segment depressions on the electrocardiogram and no perfusion abnormalities on the thallium scan. Forty-four patients underwent cardiac catheterization as the initial evaluation (Group C) and four patients underwent transplantation without a formal cardiovascular evaluation (Group D). Sixty-four of the 141 patients undergoing thallium stress testing had an adequate and normal examination (Group A). The incidence of perioperative cardiac events in this group was 2%. Seventy-seven patients (Group B) had an abnormal (n = 41) or an inadequate (n = 36) thallium stress test and most (n = 61) then underwent coronary angiography. The use of beta-blockers was the only predictor of an abnormal or inadequate thallium stress test. Forty-three percent of patients with inadequate or abnormal thallium stress tests had significant coronary artery disease on cardiac catheterization. The perioperative risk of cardiac events was not different in Group A versus Groups B, C, and D combined. Survival of Group A and B patients was not different but was significantly longer than that of Group C patients.

  8. Influence of the use of phosphate binders on serum levels of calcium phosphate in patients with chronic kidney disease undergoing hemodialysis: A retrospective and prospective study

    PubMed Central

    Setiani Agus, Lusi; Effendi, Imam; Abdillah, Syamsudin

    2013-01-01

    Hypercalcemia–hyperphosphatemia is an unavoidable consequence of end-stage chronic kidney disease and common in hemodialytic patients. Calcium carbonate (CaCO3) is one type of phosphate binder used widely and prescribed in patients undergoing hemodialysis, aiming to control the levels of calcium and phosphate. These drugs are most effective if taken with meals. This study aimed to evaluate the use of phosphate binders in hemodialysis patients and the factors that influence the success of phosphate binder therapy by experimental studies with retrospective data collection through the medical records and prospectively through the questionnaire and interviews with patients. The research was conducted in the Unit Hemodialysis building floor 8 of Cipto Mangunkusumo Hospital, Jakarta. The data were collected in a retrospective way for two months (January–February 2013) and a prospective study in March–April 2013. Patients included were stage 5 chronic kidney disease patients who underwent hemodialysis in hemodialysis ward of Cipto Mangunkusumo Hospital. Patients who had data of serum levels at the beginning of the use of calcium phosphate and the final data in 2013 got the phosphate binder therapy. Results Ninety six patients with stage 5 chronic kidney disease who underwent hemodialysis had been using phosphate binder for 3 years in average. Patient evaluation showed that hypocalcemia was obtained in 23%; normokalemia in 42.7% and hypercalcemia in 34.3%. While the percentage of patients with hipofosfatemia14, 6%, normofosfatemia 32.3% and 53.1% hyperphosphatemia. Results obtained by the prospective analysis of factors that affect the success of the use of phosphate binder therapy are related to how the routine use of phosphate binders is made by the patient. Chi square test showed a significance of 0.000 (p < 0.05), the effect of 54%. Conclusion We can conclude there are many events happening such as hyperphosphatemia in hemodialysis patients that use phosphate

  9. Changes in GABA and glutamate concentrations during memory tasks in patients with Parkinson’s disease undergoing DBS surgery

    PubMed Central

    Buchanan, Robert J.; Darrow, David P.; Meier, Kevin T.; Robinson, Jennifer; Schiehser, Dawn M.; Glahn, David C.; Nadasdy, Zoltan

    2014-01-01

    Until now direct neurochemical measurements during memory tasks have not been accomplished in the human basal ganglia. It has been proposed, based on both functional imaging studies and psychometric testing in normal subjects and in patients with Parkinson’s disease (PD), that the basal ganglia is responsible for the performance of feedback-contingent implicit memory tasks. To measure neurotransmitters, we used in vivo microdialysis during deep brain stimulation (DBS) surgery. We show in the right subthalamic nucleus (STN) of patients with PD a task-dependent change in the concentrations of glutamate and GABA during an implicit memory task relative to baseline, while no difference was found between declarative memory tasks. The five patients studied had a significant decrease in the percent concentration of GABA and glutamate during the performance of the weather prediction task (WPT). We hypothesize, based on current models of basal ganglia function, that this decrease in the concentration is consistent with expected dysfunction in basal ganglia networks in patients with PD. PMID:24639638

  10. Pretransplantation Minimal Residual Disease Predicts Survival in Patients with Mantle Cell Lymphoma Undergoing Autologous Stem Cell Transplantation in Complete Remission.

    PubMed

    Cowan, Andrew J; Stevenson, Philip A; Cassaday, Ryan D; Graf, Solomon A; Fromm, Jonathan R; Wu, David; Holmberg, Leona A; Till, Brian G; Chauncey, Thomas R; Smith, Stephen D; Philip, Mary; Orozco, Johnnie J; Shustov, Andrei R; Green, Damian J; Libby, Edward N; Bensinger, William I; Shadman, Mazyar; Maloney, David G; Press, Oliver W; Gopal, Ajay K

    2016-02-01

    Autologous stem cell transplantation (ASCT) is standard therapy for mantle cell lymphoma (MCL) in remission after induction chemotherapy, with the best results for patients in complete remission (CR). We hypothesized that evaluation of minimal residual disease (MRD) before ASCT could further stratify outcomes for these patients. Patients with MCL who underwent ASCT in clinical CR between 1996 and 2011 with pretransplantation MRD testing were eligible. Presence of a clonal IgH rearrangement, t(11; 14) by PCR or positive flow cytometry from blood or bone marrow, was considered positive. An adjusted proportional hazards model for associations with progression-free (PFS) and overall survival (OS) was performed. Of 75 MCL patients in CR, 8 (11%) were MRD positive. MRD positivity was associated with shorter OS and PFS. The median OS for MRD-negative patients was not reached, with 82% survival at 5 years, whereas for the MRD-positive patients, median OS was 3.01 years (hazard ratio [HR], 4.04; P = .009), with a median follow-up of 5.1 years. The median PFS for MRD-negative patients was not reached with 75% PFS at 5 years, whereas for MRD-positive patients, it was 2.38 years (HR, 3.69; P = .002). MRD positivity is independently associated with poor outcomes after ASCT for MCL patients in CR. PMID:26348890

  11. Anesthetic management in parturients with chronic kidney disease undergoing elective Caesarean delivery: Our experience of nine cases

    PubMed Central

    Modi, M. P.; Vora, K. S.; Parikh, G. P.; Shah, V. R.; Misra, V. V.; Jasani, A. F.

    2014-01-01

    In this retrospective study, we describe the anesthetic management and its implications in parturients with chronic kidney disease (CKD; n = 9), who underwent elective caesarean delivery. Nine parturients with CKD of various etiologies, who underwent elective Caesarean delivery, were included in this study. Spinal anest-hesia was administered in all parturients with normal coagulation profile through a 25-gauze spinal needle (Quincke) with 0.5% (H) bupivacaine in L2-3 space and T6 level was achieved. Hemodynamics and side effects such as nausea, vomiting, headache, and backache were record. The mean age was 28.22 ± 4.43 years. The mean levels of serum creatinine and serum potassium were 2.78 ± 1.29 mg/dl and 4.11 ± 0.46 meq/l, respectively. Mean baseline values of systolic blood pressure, diastolic blood pressure, and pulse rate were higher which decreased after spinal anesthesia. However, the incidence of hypotension, which required mephentermine treatment, was 11.1%. One patient had symptoms of nausea and vomiting/dizziness at the time of hypotension, which disappeared after treatment with 5 mg of intravenous mephentermine. Baseline value of PR remained high throughout the operation. Parturients with CKD with normal coagulation profile remained hemodynamically stable under spinal anesthesia with minimal side effects. However, a large number of studies are required to determine the safety of spinal anesthesia in this setting. PMID:24574626

  12. Changes in GABA and glutamate concentrations during memory tasks in patients with Parkinson's disease undergoing DBS surgery.

    PubMed

    Buchanan, Robert J; Darrow, David P; Meier, Kevin T; Robinson, Jennifer; Schiehser, Dawn M; Glahn, David C; Nadasdy, Zoltan

    2014-01-01

    Until now direct neurochemical measurements during memory tasks have not been accomplished in the human basal ganglia. It has been proposed, based on both functional imaging studies and psychometric testing in normal subjects and in patients with Parkinson's disease (PD), that the basal ganglia is responsible for the performance of feedback-contingent implicit memory tasks. To measure neurotransmitters, we used in vivo microdialysis during deep brain stimulation (DBS) surgery. We show in the right subthalamic nucleus (STN) of patients with PD a task-dependent change in the concentrations of glutamate and GABA during an implicit memory task relative to baseline, while no difference was found between declarative memory tasks. The five patients studied had a significant decrease in the percent concentration of GABA and glutamate during the performance of the weather prediction task (WPT). We hypothesize, based on current models of basal ganglia function, that this decrease in the concentration is consistent with expected dysfunction in basal ganglia networks in patients with PD. PMID:24639638

  13. Primary prevention of atrial fibrillation with beta-blockers in patients with end-stage renal disease undergoing dialysis

    PubMed Central

    Lin, Ting-Tse; Chiang, Jiun-Yang; Liao, Min-Tsun; Tsai, Chia-Ti; Hwang, Juey Jen; Chiang, Fu-Tien; Lin, Jiunn-Lee; Lin, Lian-Yu

    2015-01-01

    Current evidence suggests that beta-blocker lower the risk of development of atrial fibrillation (AF) and in-hospital stroke after cardiac surgery. This study was to assess whether beta-blockers could decrease incidence of new-onset AF in patients with end stage renal disease (ESRD). We identified patients from a nation-wide database called Registry for Catastrophic Illness, which encompassed almost 100% of the patients receiving dialysis therapy in Taiwan from 1995 to 2008. Propensity score matching and Cox’s proportional hazards regression model were used to estimate hazard ratios (HRs) for new-onset AF. Among 100066 patients, 41.7% received beta-blockers. After a median follow-up of 1500 days, the incidence of new-onset AF significantly decreased in patients treated with beta-blockers (HR = 0.483, 95% confidence interval = 0.437-0.534). The prevention of new-onset AF was significantly better in patients taking longer duration of beta-blockers therapy (P for time trend <0.001). The AF prevention effect remains robust in subgroup analyses. In conclusion, beta-blockers seem effective in the primary prevention of AF in ESRD patients. Hence, beta-blockers may be the target about upstream treatment of AF. PMID:26643783

  14. Usefulness of routine periodic fasting to lower risk of coronary artery disease in patients undergoing coronary angiography.

    PubMed

    Horne, Benjamin D; May, Heidi T; Anderson, Jeffrey L; Kfoury, Abdallah G; Bailey, Beau M; McClure, Brian S; Renlund, Dale G; Lappé, Donald L; Carlquist, John F; Fisher, Patrick W; Pearson, Robert R; Bair, Tami L; Adams, Ted D; Muhlestein, Joseph B

    2008-10-01

    Coronary artery disease (CAD) is common and multifactorial. Members of the Church of Jesus Christ of Latter-day Saints (LDS, or Mormons) in Utah may have lower cardiac mortality than other Utahns and the US population. Although the LDS proscription of smoking likely contributes to lower cardiac risk, it is unknown whether other shared behaviors also contribute. This study evaluated potential CAD-associated effects of fasting. Patients (n(1) = 4,629) enrolled in the Intermountain Heart Collaborative Study registry (1994 to 2002) were evaluated for the association of religious preference with CAD diagnosis (> or = 70% coronary stenosis using angiography) or no CAD (normal coronaries, <10% stenosis). Consequently, another set of patients (n(2) = 448) were surveyed (2004 to 2006) for the association of behavioral factors with CAD, with routine fasting (i.e., abstinence from food and drink) as the primary variable. Secondary survey measures included proscription of alcohol, tea, and coffee; social support; and religious worship patterns. In population 1 (initial), 61% of LDS and 66% of all others had CAD (adjusted [including for smoking] odds ratio [OR] 0.81, p = 0.009). In population 2 (survey), fasting was associated with lower risk of CAD (64% vs 76% CAD; OR 0.55, 95% confidence interval 0.35 to 0.87, p = 0.010), and this remained after adjustment for traditional risk factors (OR 0.46, 95% confidence interval 0.27 to 0.81, p = 0.007). Fasting was also associated with lower diabetes prevalence (p = 0.048). In regression models entering other secondary behavioral measures, fasting remained significant with a similar effect size. In conclusion, not only proscription of tobacco, but also routine periodic fasting was associated with lower risk of CAD. PMID:18805103

  15. Anxiety, locus of control, and coping strategies among end-stage renal disease patients undergoing maintenance hemodialysis.

    PubMed

    Kohli, S; Batra, P; Aggarwal, H K

    2011-07-01

    End-stage kidney disease (ESKD) patients on maintenance hemodialysis (MHD) have a lot of anxiety. Anxiety and coping are associated with the locus of control; the present investigation aimed to study the state and trait anxiety, locus of control, and active and passive coping among patients on MHD. Thirty MHD patients and 30 controls were administered State-Trait Anxiety Inventory, Rotter's Locus of Control Scale, and Coping Responses Inventory. There were significantly higher scores on state and trait anxiety, respectively (67.53 ± 10.89 vs. 59.40 ± 6.97, P < 0.01, and 62.97 ± 8.45 vs. 58.07 ± 7.06, P < 0.05), and locus of control (11.27 ± 3.55 vs. 9.04 ± 1.86, P < 0.01) in patients as compared to controls. On coping responses, patients and controls differed on positive reappraisal (54.33 ± 4.67 vs. 51.17 ± 3.12, P < 0.01), seeking guidance and support (58.07 ± 5.51 vs. 53.27 ± 4.22, P < 0.01), problem solving (51.03 ± 4.70 vs. 47.57 ± 4.73, P < 0.01), cognitive avoidance (60.27 ± 6.76 vs. 56.80 ± 4.08, P < 0.05), acceptance or resignation (61.67 ± 6.30 vs. 58.83 ± 4.23, P < 0.01), emotional discharge (68.07 ± 6.78 vs. 64.30 ± 4.50, P < 0.05), approach coping (205.57 ± 10.55 vs. 189.70 ± 11.37, P < 0.01), and avoidance coping (255.30 ± 16.45 vs. 241.10 ± 10.50, P < 0.01). A higher prevalence of anxiety trait could be the cause of anxiety in MHD patients besides the medical problems. The locus of control among patients though a mixed one was significantly more toward externalism. Thus, there is a need to identify this group well in advance and prepared not only medically but also psychologically for MHD. PMID:21886977

  16. Prevalence of airflow limitation in subjects undergoing comprehensive health examination in Japan: Survey of Chronic Obstructive pulmonary disease Patients Epidemiology in Japan

    PubMed Central

    Omori, Hisamitsu; Kaise, Toshihiko; Suzuki, Takeo; Hagan, Gerry

    2016-01-01

    Purpose There are still evidence gaps on the prevalence of airflow limitation in Japan. The purpose of this survey was to estimate the prevalence of airflow limitation among healthy subjects in Japan and to show what proportion of subjects with airflow limitation had been diagnosed with chronic obstructive pulmonary disease (COPD). Subjects and methods This was an observational, cross-sectional survey targeting multiple regions of Japan. Subjects aged 40 years or above who were undergoing comprehensive health examination were recruited from 14 centers in Japan. Airflow limitation was defined as having forced expiratory volume in 1 second/forced vital capacity less than 70%. Results In a total of 22,293 subjects, airflow limitation was most prevalent in subjects aged over 60 years (8.7%), but was also observed in subjects aged 50–59 years (3.1%) and 40–49 years (1.7%). Overall prevalence was 4.3%. Among subjects with smoking history (n=10,981), the prevalence of airflow limitation in each age group (12.8% in those aged over 60 years, 4.4% in those aged 50–59 years, and 2.2% in those aged 40–49 years) and overall prevalence (6.1%) were higher than that of total subjects. Of the smokers with airflow limitation, 9.4% had been diagnosed with COPD/emphysema and 27.3% with other respiratory diseases. Conclusion Among smokers undergoing comprehensive health examination, prevalence of airflow limitation reached 12.8% in those aged over 60 years and airflow limitation was observed in subjects aged 40–59 years as well, though their prevalence was lower than that in subjects aged over 60 years. We demonstrated that a significant proportion of smokers with airflow limitation had not been diagnosed with COPD/emphysema, suggesting that some of them can be diagnosed with COPD or other respiratory diseases by a detailed examination after comprehensive health examination. Screening for subjects at risk of COPD by spirometry in comprehensive health examination starting at

  17. Rituximab in Preventing Acute Graft-Versus-Host Disease in Patients Undergoing a Donor Stem Cell Transplant for Hematologic Cancer

    ClinicalTrials.gov

    2014-05-28

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Blastic Phase Chronic Myelogenous Leukemia; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Graft Versus Host Disease; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III

  18. Different Risk of Common Gastrointestinal Disease Between Groups Undergoing Hemodialysis or Peritoneal Dialysis or With Non-End Stage Renal Disease

    PubMed Central

    Lee, Yi-Che; Hung, Shih-Yuan; Wang, Hsi-Hao; Wang, Hao-Kuang; Lin, Chi-Wei; Chang, Min-Yu; Ho, Li-Chun; Chen, Yi-Ting; Wu, Ching-Fang; Chen, Ho-Ching; Wang, Wei-Ming; Sung, Junne-Ming; Chiou, Yuan-Yow; Lin, Sheng-Hsiang

    2015-01-01

    Abstract Peritoneal dialysis (PD) is one type of renal replacement therapy, but potential peritoneal damage and gastrointestinal (GI) tract adverse effects during long-term exposure to bio-incompatible dialysate remain a concern. Although GI disease frequently occurs in dialysis patients, whether the risk of GI diseases differs among PD and hemodialysis (HD) or non-uremic groups is still uncertain. In this retrospective cohort study, data were obtained from the National Health Insurance Research Database, which includes almost all dialysis patients in Taiwan. Between 2000 and 2009, a total of 1791 PD and 8955 HD incident patients were enrolled and matched for age and sex or for propensity score. In addition, a comparison cohort of 8955 non-uremic patients was also selected. Individuals were monitored for the occurrence of common GI diseases until 2010, and data were analyzed using several different models. Generally speaking, the results showed that the risk of gastroesophageal reflux, intestinal obstruction or adhesions, and abdominal hernia was significantly higher in the PD group, whereas the risk of peptic ulcer disease and lower GI diverticula and bleeding was significantly greater in the HD group. Meanwhile, the risk of mesenteric ischemia, liver cirrhosis, and acute pancreatitis was higher in dialysis patients, but was not significantly different between the PD and HD groups; moreover, the risk of appendicitis in the PD group appeared to be lower than that in the HD group. In conclusion, dialysis patients have a higher risk of most common GI diseases, and PD and HD modalities are associated with different GI diseases. PMID:26356710

  19. Different Risk of Common Gastrointestinal Disease Between Groups Undergoing Hemodialysis or Peritoneal Dialysis or With Non-End Stage Renal Disease: A Nationwide Population-Based Cohort Study.

    PubMed

    Lee, Yi-Che; Hung, Shih-Yuan; Wang, Hsi-Hao; Wang, Hao-Kuang; Lin, Chi-Wei; Chang, Min-Yu; Ho, Li-Chun; Chen, Yi-Ting; Wu, Ching-Fang; Chen, Ho-Ching; Wang, Wei-Ming; Sung, Junne-Ming; Chiou, Yuan-Yow; Lin, Sheng-Hsiang

    2015-09-01

    Peritoneal dialysis (PD) is one type of renal replacement therapy, but potential peritoneal damage and gastrointestinal (GI) tract adverse effects during long-term exposure to bio-incompatible dialysate remain a concern. Although GI disease frequently occurs in dialysis patients, whether the risk of GI diseases differs among PD and hemodialysis (HD) or non-uremic groups is still uncertain.In this retrospective cohort study, data were obtained from the National Health Insurance Research Database, which includes almost all dialysis patients in Taiwan. Between 2000 and 2009, a total of 1791 PD and 8955 HD incident patients were enrolled and matched for age and sex or for propensity score. In addition, a comparison cohort of 8955 non-uremic patients was also selected. Individuals were monitored for the occurrence of common GI diseases until 2010, and data were analyzed using several different models.Generally speaking, the results showed that the risk of gastroesophageal reflux, intestinal obstruction or adhesions, and abdominal hernia was significantly higher in the PD group, whereas the risk of peptic ulcer disease and lower GI diverticula and bleeding was significantly greater in the HD group. Meanwhile, the risk of mesenteric ischemia, liver cirrhosis, and acute pancreatitis was higher in dialysis patients, but was not significantly different between the PD and HD groups; moreover, the risk of appendicitis in the PD group appeared to be lower than that in the HD group.In conclusion, dialysis patients have a higher risk of most common GI diseases, and PD and HD modalities are associated with different GI diseases. PMID:26356710

  20. Diffuse Interstitial Brain Edema in Patients With End-Stage Renal Disease Undergoing Hemodialysis: A Tract-Based Spatial Statistics Study

    PubMed Central

    Kong, Xiang; Wen, Ji-qiu; Qi, Rong-feng; Luo, Song; Zhong, Jian-hui; Chen, Hui-juan; Ji, Gong-jun; Lu, Guang Ming; Zhang, Long Jiang

    2014-01-01

    Abstract To investigate white matter (WM) alterations and their correlation with cognition function in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) using diffusion tensor imaging (DTI) with tract-based spatial statistics (TBSS) approach. This prospective HIPAA-complaint study was approved by our institutional review board. Eighty HD ESRD patients and 80 sex- and age-matched healthy controls were included. Neuropsychological (NP) tests and laboratory tests, including serum creatinine and urea, were performed. DTI data were processed to obtain fractional anisotropy (FA) and mean diffusivity (MD) maps with TBSS. FA and MD difference between the 2 groups were compared. We also explored the associations of FA values in WM regions of lower FA with ages, NP tests, disease, and dialysis durations, serum creatinine and urea levels of ESRD patients. Compared with controls, HD ESRD patients had lower FA value in the corpus callosum, bilateral corona radiate, posterior thalamic radiation, left superior longitudinal fasciculus, and right cingulum (P < 0.05, FWE corrected). Almost all WM regions had increased MD in HD ESRD patients compared with controls (P < 0.05, FWE corrected). In some regions with lower FA, FA values showed moderate correlations with ages, NP tests, and serum urea levels. There was no correlation between FA values and HD durations, disease durations, and serum creatinine levels of ESRD patients (all P > 0.05). Diffuse interstitial brain edema and moderate WM integrity disruption occurring in HD ESRD patients, which correlated with cognitive dysfunction, and serum urea levels might be a risk factor for these WM changes. PMID:25526483

  1. Anti-Hyperglycemic Agents and New-Onset Acute Myocardial Infarction in Diabetic Patients with End-Stage Renal Disease Undergoing Dialysis

    PubMed Central

    Lin, Ting-Tse; Wu, Chih-Chen; Yang, Yao-Hsu; Lin, Lian-Yu; Lin, Jiunn-Lee; Chen, Pau-Chung; Hwang, Juey-Jen

    2016-01-01

    Background Diabetes and chronic kidney disease (CKD) are a high-stakes combination for cardiovascular disease. Patients with decreased kidney function and end-stage renal disease (ESRD) have increased risk of hypoglycemia when attaining better glycemic control, leading to higher risk of myocardial infarction (MI). For these patients, which kinds of anti-hyperglycemic agents would be associated with higher risk of MI is not clear. Methods We identified patients from a nation-wide database called Registry for Catastrophic Illness, which encompassed almost 100% of the patients receiving dialysis therapy in Taiwan from 1995 to 2008. Patients with diabetes and ESRD were selected as the study cohort. Propensity score adjustment and Cox's proportional hazards regression model were used to estimate the hazard ratios (HRs) for new-onset MI. Results Among 15,161 patients, 39% received insulin, 40% received sulfonylureas, 18% received meglitinides and 3% received thiazolidinedione (TZD). After a median follow-up of 1,357 days, the incidence of MI was significant increase in patients taking sulfonylureas (HR = 1.523, 95% confidence interval [CI] = 1.331–1.744), meglitinides (HR = 1.251, 95% CI = 1.048–1.494) and TZD (HR = 1.515, 95% CI = 1.071–2.145) by using patients receiving insulin therapy as the reference group. The risk of MI remains higher in other three groups in subgroup analyses. Conclusions In conclusion, among diabetic patients with ESRD undergoing dialysis, the use of sulfonylureas, meglitinides and TZD are associated with higher risk of new-onset MI as compared with insulin. PMID:27513562

  2. Infusing CD19-Directed T Cells to Augment Disease Control in Patients Undergoing Autologous Hematopoietic Stem-Cell Transplantation for Advanced B-Lymphoid Malignancies

    PubMed Central

    Kebriaei, Partow; Huls, Helen; Jena, Bipulendu; Munsell, Mark; Jackson, Rineka; Lee, Dean A.; Hackett, Perry B.; Rondon, Gabriela; Shpall, Elizabeth; Champlin, Richard E.

    2012-01-01

    Abstract Limited curative treatment options exist for patients with advanced B-lymphoid malignancies, and new therapeutic approaches are needed to augment the efficacy of hematopoietic stem-cell transplantation (HSCT). Cellular therapies, such as adoptive transfer of T cells that are being evaluated to target malignant disease, use mechanisms independent of chemo- and radiotherapy with nonoverlapping toxicities. Gene therapy is employed to generate tumor-specific T cells, as specificity can be redirected through enforced expression of a chimeric antigen receptor (CAR) to achieve antigen recognition based on the specificity of a monoclonal antibody. By combining cell and gene therapies, we have opened a new Phase I protocol at the MD Anderson Cancer Center (Houston, TX) to examine the safety and feasibility of administering autologous genetically modified T cells expressing a CD19-specific CAR (capable of signaling through chimeric CD28 and CD3-ζ) into patients with high-risk B-lymphoid malignancies undergoing autologous HSCT. The T cells are genetically modified by nonviral gene transfer of the Sleeping Beauty system and CAR+ T cells selectively propagated in a CAR-dependent manner on designer artificial antigen-presenting cells. The results of this study will lay the foundation for future protocols including CAR+ T-cell infusions derived from allogeneic sources. PMID:22107246

  3. Should spinocerebellar ataxias be included in the differential diagnosis for Huntington's diseases-like syndromes?

    PubMed

    Pedroso, José Luiz; de Freitas, Maria Eliza Thomaz; Albuquerque, Marcus Vinicius Cristino; Saraiva-Pereira, Maria Luiza; Jardim, Laura Bannach; Barsottini, Orlando G P

    2014-12-15

    In this article, we describe three patients with different spinocerebellar ataxia (SCA) subtypes presenting with unusual movement disorders predominantly characterized by choreoathetosis, which, together with their autosomal dominant pattern of inheritance, resembled the Huntington-like syndromes. From a large SCA cohort, we have observed chorea in 1/35 SCA2, 1/112 SCA3/MJD, and 1/30 SCA7 patients. Twenty-eight patients with SCA1, 11 patients with SCA6, and 3 patients with SCA10 were also evaluated, and none of them presented chorea. We provide a brief report of the three cases, with a video demonstrating chorea. Although a debate regarding the frequency of chorea in SCA patients is a fact, its occurrence, together with the autosomal dominant pattern of inheritance, clearly imposes SCA in the differentials of Huntington-like syndromes. There is some debate about what to include in a list of Huntington-like disorders, with several review articles about Huntington-like syndromes not including SCA in the differential diagnosis, except for SCA17. We believe that SCAs-at least SCA1, SCA2, SCA3/MJD, SCA7 and DRPLA-should be thought in the diagnostic workout of at least the atypical cases, such as those presented in this report. PMID:25456461

  4. Evidence for emerging parasites and pathogens influencing outbreaks of stress-related diseases like chalkbrood.

    PubMed

    Hedtke, Kati; Jensen, Per Moestrup; Jensen, Annette Bruun; Genersch, Elke

    2011-11-01

    In agriculture, honey bees play a critical role as commercial pollinators of crop monocultures which depend on insect pollination. Hence, the demise of honey bee colonies in Europe, USA, and Asia caused much concern and initiated many studies and research programmes aiming at elucidating the factors negatively affecting honey bee health and survival. Most of these studies look at individual factors related to colony losses. In contrast, we here present our data on the interaction of pathogens and parasites in honey bee colonies. We performed a longitudinal cohort study over 6 years by closely monitoring 220 honey bee colonies kept in 22 apiaries (ten randomly selected colonies per apiary). Observed winter colony losses varied between 4.8% and 22.4%; lost colonies were replaced to ensure a constant number of monitored colonies over the study period. Data on mite infestation levels, infection with viruses, Nosema apis and Nosema ceranae, and recorded outbreaks of chalkbrood were continuously collected. We now provide statistical evidence (i) that Varroa destructor infestation in summer is related to DWV infections in autumn, (ii) that V. destructor infestation in autumn is related to N. apis infection in the following spring, and most importantly (iii) that chalkbrood outbreaks in summer are related to N. ceranae infection in the preceding spring and to V. destructor infestation in the same season. These highly significant links between emerging parasites/pathogens and established pathogens need further experimental proof but they already illustrate the complexity of the host-pathogen-interactions in honey bee colonies. PMID:21906600

  5. Mucosal Disease-Like Syndrome in a Calf Persistently Infected by Hobi-Like Pestivirus

    PubMed Central

    Lanave, Gianvito; Lucente, Maria Stella; Mari, Viviana; Varello, Katia; Losurdo, Michele; Larocca, Vittorio; Bozzetta, Elena; Cavaliere, Nicola; Martella, Vito; Buonavoglia, Canio

    2014-01-01

    A calf persistently infected with Hobi-like pestivirus displayed severe clinical signs and subsequently died. Gross lesions and histopathological changes were suggestive of hemorrhagic and necrotic inflammation involving several tissues. A Hobi-like pestivirus pair was isolated from the dead calf, i.e., cytopathogenic (CP) and noncytopathogenic (NCP) strains strictly related to each other and to Italian prototype isolates at the genetic level. Two biotype-specific real-time reverse transcription-PCR assays determined the time of the emergence of the CP virus as 1 month before the calf's death. This highest RNA titers were reached in lymphoid and nervous system tissues, whereas only traces of CP viral RNA were found in blood. In contrast, great NCP virus loads were present in all tissues and biological fluids. The present report provides new insights into the pathogenesis and molecular mechanisms of this emerging group of pestiviruses. PMID:24899039

  6. A systematic review and meta-analysis—does chronic obstructive pulmonary disease predispose to bronchopleural fistula formation in patients undergoing lung cancer surgery?

    PubMed Central

    Li, Shuang-Jiang; Zhou, Xu-Dong; Huang, Jian; Liu, Jing; Tian, Long

    2016-01-01

    Background we conducted this systematic meta-analysis to determine the association between chronic obstructive pulmonary disease (COPD) and risk of bronchopleural fistula (BPF) in patients undergoing lung cancer surgery. Methods Literature retrieval was performed in PubMed, Embase and the Web of Science to identify the full-text articles that met our eligibility criteria. Odds ratio (OR) with 95% confidence interval (CI) served as the summarized statistics. Q-test and I2-statistic were used to evaluate the level of heterogeneity. Sensitivity analysis was performed to further examine the stability of pooled OR. Publication bias was detected by both Begg’s test and Egger’s test. Results Eight retrospective observational studies were included into this meta-analysis. The overall summarized OR was 2.03 (95% CI: 1.44–2.86; P<0.001), revealing that COPD was significantly associated with the risk of BPF after lung cancer surgery. In subgroup analysis, the relationship between COPD and BPF occurrence remained statistically prominent in the subgroups stratified by statistical analysis (univariate analysis, OR: 1.91; 95% CI: 1.35–2.69; P<0.001; multivariate analysis, OR: 3.18; 95% CI: 1.95–5.19; P<0.001), operative modes (pneumonectomy, OR: 2.11; 95% CI: 1.15–3.87; P=0.016) and in non-Asian populations (OR: 2.36; 95% CI: 1.18–4.73; P=0.016). No significant impact of COPD on BPF risk was observed in Asian patients (OR: 1.48; 95% CI: 0.85–2.57; P=0.16). No significant heterogeneity or publication bias was discovered across the included studies. Conclusions Our meta-analysis indicates that COPD can significantly predispose to BPF formation in patients undergoing lung cancer surgery. Because some limitations still exist in this meta-analysis, our findings should be further verified and modified in the future. PMID:27499951

  7. Efficacy of a Human Amniotic Tissue-derived Allograft, NuCel, in Patients Undergoing Posteriolateral Lumbar Fusions for Degenerative Disc Disease

    ClinicalTrials.gov

    2016-03-28

    Lumbar Degenerative Disc Disease; Spinal Stenosis; Spondylolisthesis; Spondylosis; Intervertebral Disk Displacement; Intervertebral Disk Degeneration; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Spondylolysis

  8. Randomized Trial of Complete Versus Lesion-Only Revascularization in Patients Undergoing Primary Percutaneous Coronary Intervention for STEMI and Multivessel Disease

    PubMed Central

    Gershlick, Anthony H.; Khan, Jamal Nasir; Kelly, Damian J.; Greenwood, John P.; Sasikaran, Thiagarajah; Curzen, Nick; Blackman, Daniel J.; Dalby, Miles; Fairbrother, Kathryn L.; Banya, Winston; Wang, Duolao; Flather, Marcus; Hetherington, Simon L.; Kelion, Andrew D.; Talwar, Suneel; Gunning, Mark; Hall, Roger; Swanton, Howard; McCann, Gerry P.

    2015-01-01

    Background The optimal management of patients found to have multivessel disease while undergoing primary percutaneous coronary intervention (P-PCI) for ST-segment elevation myocardial infarction is uncertain. Objectives CvLPRIT (Complete versus Lesion-only Primary PCI trial) is a U.K. open-label randomized study comparing complete revascularization at index admission with treatment of the infarct-related artery (IRA) only. Methods After they provided verbal assent and underwent coronary angiography, 296 patients in 7 U.K. centers were randomized through an interactive voice-response program to either in-hospital complete revascularization (n = 150) or IRA-only revascularization (n = 146). Complete revascularization was performed either at the time of P-PCI or before hospital discharge. Randomization was stratified by infarct location (anterior/nonanterior) and symptom onset (≤3 h or >3 h). The primary endpoint was a composite of all-cause death, recurrent myocardial infarction (MI), heart failure, and ischemia-driven revascularization within 12 months. Results Patient groups were well matched for baseline clinical characteristics. The primary endpoint occurred in 10.0% of the complete revascularization group versus 21.2% in the IRA-only revascularization group (hazard ratio: 0.45; 95% confidence interval: 0.24 to 0.84; p = 0.009). A trend toward benefit was seen early after complete revascularization (p = 0.055 at 30 days). Although there was no significant reduction in death or MI, a nonsignificant reduction in all primary endpoint components was seen. There was no reduction in ischemic burden on myocardial perfusion scintigraphy or in the safety endpoints of major bleeding, contrast-induced nephropathy, or stroke between the groups. Conclusions In patients presenting for P-PCI with multivessel disease, index admission complete revascularization significantly lowered the rate of the composite primary endpoint at 12 months compared with treating only the

  9. Immunologic Diagnostic Blood Test in Predicting Side-Effects in Patients Undergoing a Donor Stem Cell Transplant for Hematologic Cancer or Other Diseases

    ClinicalTrials.gov

    2011-03-03

    Chronic Myeloproliferative Disorders; Graft Versus Host Disease; Infection; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Neuroblastoma; Therapy-related Toxicity

  10. Peripheral Arterial Disease

    MedlinePlus

    Peripheral arterial disease (PAD) happens when there is a narrowing of the blood vessels outside of your heart. The cause of ... smoking. Other risk factors include older age and diseases like diabetes, high blood cholesterol, high blood pressure, ...

  11. Sirolimus, Tacrolimus, Thymoglobulin and Rituximab as Graft-versus-Host-Disease Prophylaxis in Patients Undergoing Haploidentical and HLA Partially Matched Donor Hematopoietic Cell Transplantation

    ClinicalTrials.gov

    2015-12-09

    Chronic Myeloproliferative Disorders; Graft Versus Host Disease; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms

  12. Sleep disorders in patients with end-stage renal disease undergoing dialysis: comparison between hemodialysis, continuous ambulatory peritoneal dialysis and automated peritoneal dialysis.

    PubMed

    Losso, Ricardo L M; Minhoto, Gisele R; Riella, Miguel C

    2015-02-01

    Sleep disorders for patients on dialysis are significant causes of a poorer quality of life and increased morbidity and mortality. No study has evaluated patients undergoing automated peritoneal dialysis (APD) to assess their sleep disorders compared to hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). A total of 166 clinically stable patients who had been on dialysis for at least 3 months were randomly selected for the study and divided into HD, CAPD or APD. Socio-demographic, clinical and laboratory parameters and self-administered questionnaires were collected for the investigation of insomnia, restless legs syndrome (RLS), bruxism, rapid eye movement sleep behavior disorder, excessive daytime sleepiness (EDS), obstructive sleep apnea syndrome (OSAS), sleepwalking, sleep hygiene, depression and anxiety. Insomnia was detected in more than 80 % of patients on the three modalities. OSAS was lower for patients on HD (36 %) than on CAPD (65 %) (p < 0.01) or APD (60 %) (p < 0.04). Patients on APD were more likely to have RLS compared to those on HD or CAPD (p < 0.04) (50 vs. 23 vs. 33 %). No differences among the modalities were found in bruxism, EDS, sleepwalking, sleep hygiene, depression or anxiety. ESRD patients undergoing any one of the three dialysis modalities studied had a high prevalence of sleep disorders. Patients on HD had a lower proportion of OSAS than those on CAPD and APD, which is most likely attributed to their lower body mass indices. The possible causes of higher RLS rates in APD patients have not been established. PMID:25358390

  13. Sirolimus, Tacrolimus, and Antithymocyte Globulin in Preventing Graft-Versus-Host Disease in Patients Undergoing a Donor Stem Cell Transplant For Hematological Cancer

    ClinicalTrials.gov

    2014-09-03

    Chronic Myeloproliferative Disorders; Graft Versus Host Disease; Infection; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Precancerous Condition; Secondary Myelofibrosis; Small Intestine Cancer

  14. Comparison of Bare-Metal Stent and Drug-Eluting Stent for the Treatment of Patients Undergoing Percutaneous Coronary Intervention for Unprotected Left Main Coronary Artery Disease – Long-Term Result from a Single Center Experience

    PubMed Central

    Lai, Chih-Hung; Lee, Wen-Lieng; Sung, Shih-Hsien; Hsu, Pai-Feng; Chen, Ying-Hwa; Chan, Wan-Leong; Lin, Shing-Jong; Lu, Tse-Min

    2015-01-01

    Background Percutaneous coronary intervention (PCI) has become an alternative treatment for left main (LM) coronary artery disease. The aim of our study was to compare long-term clinical outcomes of patients undergoing unprotected LM PCI with bare-metal stent (BMS) or drug-eluting stent (DES) in a high-risk population. Methods and Results We enrolled 223 consecutive patients with unprotected LM coronary artery disease undergoing PCI (mean age: 71.1 ± 11.2 years, 187 male), including 94 patients receiving BMS and 129 patients receiving DES. The patients receiving DES had a significantly higher SYNTAX score (p = 0.05). During the mean follow-up period of 2.5 years, there were 31 cardiovascular deaths (BMS: 21 cases, DES: 10 cases, p = 0.04 by log-rank test), 56 major adverse cardiovascular events (MACE, including cardiovascular death, non-fatal myocardial infarction (MI) and clinical-driven target lesion revascularization; BMS: 33 cases, DES: 23 cases, p = 0.03 by log-rank test) and 6 cases with definite/probable stent thrombosis (BMS: 5 cases, DES: 1 cases, p = 0.09). In multivariate Cox analysis, the use of DES was identified as an independent protective factor against cardiovascular death [hazard ratio (HR) = 0.34, 95% confidence interval (Cl) = 0.15-0.79, p = 0.01] and MACE (HR = 0.50, 95% CI = 0.28-0.88, p = 0.02). The clinical outcome analyses in propensity-score matched the cohort (87 matched pair of patients receiving BMS and DES) and yielded similar results. Conclusions In the general practice among a high-risk population undergoing unprotected LM PCI, the use of DES appeared to be beneficial in reducing the risk of long-term cardiovascular death and MACE. PMID:27122897

  15. Asymmetric dimethylarginine but not osteoprotegerin correlates with disease severity in patients with moderate-to-severe psoriasis undergoing anti-tumor necrosis factor-α therapy.

    PubMed

    Pina, Trinitario; Genre, Fernanda; Lopez-Mejias, Raquel; Armesto, Susana; Ubilla, Begoña; Mijares, Veronica; Dierssen-Sotos, Trinidad; Corrales, Alfonso; Gonzalez-Lopez, Marcos A; Gonzalez-Vela, Maria C; Blanco, Ricardo; Hernández, Jose L; Llorca, Javier; Gonzalez-Gay, Miguel A

    2016-04-01

    Patients with psoriasis, in particular those with severe disease, have an increased risk of cardiovascular (CV) events compared with the general population. The aim of the present study is to determine whether correlation between asymmetric dimethylarginine (ADMA) and osteoprotegerin (OPG), two biomarkers associated with CV disease, and disease severity may exist in patients with moderate-to-severe psoriasis. We also aimed to establish if baseline serum levels of these two biomarkers could correlate with the degree of change in the clinical parameters of disease severity following the use of anti-tumor necrosis factor (TNF)-α therapy in these patients. This was a prospective study on a series of consecutive non-diabetic patients with moderate-to-severe psoriasis who completed 6 months of therapy with anti-TNF-α-adalimumab. Patients with kidney disease, hypertension or body mass index of 35 kg/m(2) or more were excluded. Metabolic and clinical evaluation was performed immediately prior to the onset of treatment and at month 6. Twenty-nine patients were assessed. Unlike OPG, a significant positive correlation between ADMA and resistin serum levels was found at the onset of adalimumab and also after 6 months of biologic therapy. We also observed a positive correlation between the percent of body surface area affected (BSA) and ADMA levels obtained before the onset of adalimumab and a negative correlation between baseline ADMA levels and a 6-month BSA change compared with baseline results. In patients with moderate-to-severe psoriasis, ADMA levels correlate with clinical markers of disease severity. PMID:26364678

  16. Gynecological diseases in rural India: A critical appraisal of indications and route of surgery along with histopathology correlation of 922 women undergoing major gynecological surgery

    PubMed Central

    Sharma, Chanderdeep; Sharma, Manupriya; Raina, Rashmi; Soni, Anjali; Chander, Bal; Verma, Suresh

    2014-01-01

    Objective: The aim of the study was to generate baseline data for indications of gynecological surgeries, and to assess route of surgery and histopathology correlation in women undergoing major gynecological surgery in a rural tertiary level teaching hospital in India. Materials and Methods: Surgical indications, route of surgery and histopathology findings were reviewed and analyzed retrospectively, in 922 patients (≥35 years age) who underwent gynecological surgery at Dr. Rajendra Prasad Government Medical College, Kangra, Himachal Pradesh, India from January 1, 2011 to May 31, 2013. Results: Of 922 surgeries, 65 had malignancy (7%). Pelvic organ prolapse (POP) (32.3%) and leiomyoma uterus (29%) were two most common benign indications for hysterectomy. Ovarian tumors were present in 13% (25% of these were malignant). Postmenopausal bleeding (PMB) was seen in 5.5% (55% of these were malignant). Conclusions: All except 10% surgeries were done in the absence of definite histopathology diagnosis that is dysfunctional uterine bleeding (n = 42 [45%]), chronic pelvic pain/severe dysmenorrhea (n = 34 [36%]) and recurrent PMB (n = 17 [19%]). Majority of surgeries had histopathological correlation except for six cases (0.6%) of malignancy, which were missed on initial work-up. Majority of the surgeries were done abdominally. In rural areas of developing countries poverty, lack of regular follow-up, resource constraints and lack of technical skills (with respect to laparoscopic/robotic surgeries) pose major challenge in providing quality health care. PMID:24970982

  17. Cognitive and Affective Changes in Mild to Moderate Alzheimer’s Disease Patients Undergoing Switch of Cholinesterase Inhibitors: A 6-Month Observational Study

    PubMed Central

    Spalletta, Gianfranco; Caltagirone, Carlo; Padovani, Alessandro; Sorbi, Sandro; Attar, Mahmood; Colombo, Delia; Cravello, Luca

    2014-01-01

    Patients with Alzheimer’s disease after an initial response to cholinesterase inhibitors may complain a later lack of efficacy. This, in association with incident neuropsychiatric symptoms, may worsen patient quality of life. Thus, the switch to another cholinesterase inhibitor could represent a valid therapeutic strategy. The aim of this study was to investigate the effectiveness of the switch from one to another cholinesterase inhibitor on cognitive and affective symptoms in mild to moderate Alzheimer disease patients. Four hundred twenty-three subjects were included from the EVOLUTION study, an observational, longitudinal, multicentre study conducted on Alzheimer disease patients who switched to different cholinesterase inhibitor due either to lack/loss of efficacy or response, reduced tolerability or poor compliance. All patients underwent cognitive and neuropsychiatric assessments, carried out before the switch (baseline), and at 3 and 6-month follow-up. A significant effect of the different switch types was found on Mini-Mental State Examination score during time, with best effectiveness on mild Alzheimer’s disease patients switching from oral cholinesterase inhibitors to rivastigmine patch. Depressive symptoms, when measured using continuous Neuropsychiatric Inventory values, decreased significantly, while apathy symptoms remained stable over the 6 months after the switch. However, frequency of both depression and apathy, when measured categorically using Neuropsychiatric Inventory cut-off scores, did not change significantly during time. In mild to moderate Alzheimer disease patients with loss of efficacy and tolerability during cholinesterase inhibitor treatment, the switch to another cholinesterase inhibitor may represent an important option for slowing cognitive deterioration. The evidence of apathy stabilization and the positive tendency of depressive symptom improvement should definitively be confirmed in double-blind controlled studies. PMID

  18. Marek's disease virus undergoes complete morphogenesis after reactivation in a T-lymphoblastoid cell line transformed by recombinant fluorescent marker virus.

    PubMed

    Denesvre, Caroline; Rémy, Sylvie; Trapp-Fragnet, Laetitia; Smith, Lorraine P; Georgeault, Sonia; Vautherot, Jean-François; Nair, Venugopal

    2016-02-01

    T-lymphocytes are central targets of Marek's disease, a major chicken disease induced by the oncogenic alphaherpesvirus Marek's disease virus (MDV). T-lymphocyte infection is also associated with immunosuppression and virus latency. To decipher viral morphogenesis in T-lymphocytes, we used the recombinant vRB-1B 47EGFP marker virus to generate a new lymphoblastoid cell line, 3867K, that exhibited typical properties of other MDV-transformed chicken cell lines in term of cell markers, reactivation rate and infectivity. Examination of reactivating EGFP-positive 3867K cells by transmission electron microscopy revealed the presence of most types of herpesvirus particles inside the cells but no extracellular ones. Quantification of virion types indicated only 5% cytoplasmic particles, with 0.5% being mature. This study demonstrated that MDV morphogenesis is complete upon reactivation in T-lymphocytes, albeit with poor efficiency, with a defect in the exit of virions from the nucleus and secondary envelopment, as occurs in infected fibroblasts. PMID:26612074

  19. 78 FR 52770 - Agency Forms Undergoing Paperwork Reduction Act Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-26

    ... HUMAN SERVICES Centers for Disease Control and Prevention Agency Forms Undergoing Paperwork Reduction... Collection of Qualitative Feedback on Agency Service Delivery--NEW--Centers for Disease Control and Prevention (CDC), Office of Surveillance, Epidemiology, and Laboratory Services (OSELS), Public...

  20. 78 FR 69092 - Agency Forms Undergoing Paperwork Reduction Act Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-18

    ...: Control Numbers 0920- 0128, (Congenital Syphilis Surveillance), 0920-0819 (Nationally Notifiable Sexually... HUMAN SERVICES Centers for Disease Control and Prevention Agency Forms Undergoing Paperwork Reduction Act Review The Centers for Disease Control and Prevention (CDC) publishes a list of...

  1. Late-onset Krabbe disease is predominant in Japan and its mutant precursor protein undergoes more effective processing than the infantile-onset form.

    PubMed

    Hossain, Mohammad Arif; Otomo, Takanobu; Saito, Seiji; Ohno, Kazuki; Sakuraba, Hitoshi; Hamada, Yusuke; Ozono, Keiichi; Sakai, Norio

    2014-01-25

    Krabbe disease is an autosomal recessive leukodystrophy caused by the deficiency of the galactocerebrosidase (GALC) enzyme. It is pathologically characterized by demyelination of the central and peripheral nervous systems by accumulation of galactosylsphingosine. To date, more than 120 mutations in the GALC gene have been reported worldwide and genotype-phenotype correlations have been reported in some types of mutations. In this study, we analyzed 22 unreported Japanese patients with Krabbe disease and summarized a total of 51 Japanese patients, including 29 previously reported patients. To elucidate how GALC mutations impair enzymatic activity, multiple disease-causing mutations including common mutations and polymorphisms were investigated for enzymatic activity and precursor processing ability with transient expression system. We also performed 3-D enzyme structure analysis to determine the effect of each new mutation. Five novel mutations were detected including one deletion c.1808delT [p.L603X], one nonsense mutation c.1023C>G [p.Y341X], and three missense mutations c.209T>C [p.L70P], c.1054G>A [p.G352R], and c.1937G>C [p.G646A]. For the total of 51 patients, 59% had late-onset forms of Krabbe disease. Seven common mutations accounted for 58% of mutant alleles of patients with Krabbe disease in Japan. Infantile-onset mutations had almost no enzyme activity, while late-onset mutations had 4%-20% of normal enzyme activity. The processing rate of precursor GALC protein to mature form was slower for infantile-onset mutations. Heat stability of the mutant proteins revealed that p.G270D was more stable compared to the other mutations. The constructed 3D-model showed that the residues for Krabbe mutations were less solvent-accessible and located in the core region of GALC protein. In conclusion, we have demonstrated that the most common phenotype in Japan is the late-onset type, that the enzyme activity for GALC mutants is correlated with mutational severity, and

  2. Thymoglobulin prevents chronic graft-versus-host disease, chronic lung dysfunction, and late transplant-related mortality: long-term follow-up of a randomized trial in patients undergoing unrelated donor transplantation.

    PubMed

    Bacigalupo, Andrea; Lamparelli, Teresa; Barisione, Giovanni; Bruzzi, Paolo; Guidi, Stefano; Alessandrino, Paolo Emilio; di Bartolomeo, Paolo; Oneto, Rosi; Bruno, Barbara; Sacchi, Nicoletta; van Lint, Maria Teresa; Bosi, Alberto

    2006-05-01

    This is an update of a randomized study on antithymocyte globulin (ATG; Thymoglobulin) before transplantation in patients undergoing unmanipulated marrow transplantation from unrelated donors. The median follow-up for surviving patients is 5.7 years. At last follow-up, chronic graft-versus-host disease (GVHD) was scored in 60% of non-ATG and in 37% of ATG patients (P=.05), and extensive chronic GVHD was present in 41% and 15%, respectively (P=.01). Chronic lung dysfunction was diagnosed in 51% versus 19% of patients (P=.005). Forced vital capacity decreased significantly with time in non-ATG patients (P=.005), but not in patients who received ATG (P=.30). The proportion of patients with Karnofsky scores of >or=90% at 4 years was 57% versus 89% in non-ATG versus ATG patients (P=.03). The actuarial 6-year survival for all patients randomized was 31% versus 44% (non-ATG versus ATG; P=.80). The cumulative incidence of transplant-related mortality was 51% versus 41% (P=.70) and of relapse was 32% versus 40% (P=.90). For patients who survived 1 year, transplant-related mortality was 25% versus 3% (P=.03), and actuarial survival was 58% versus 85% (P=.09). In conclusion, the addition of ATG to cyclosporine/methotrexate provides significant protection against extensive chronic GVHD and chronic lung dysfunction, reduces late transplant mortality, and improves quality of life in patients undergoing unrelated donor transplantation. PMID:16635791

  3. Emotion recognition in early Parkinson’s disease patients undergoing deep brain stimulation or dopaminergic therapy: a comparison to healthy participants

    PubMed Central

    McIntosh, Lindsey G.; Mannava, Sishir; Camalier, Corrie R.; Folley, Bradley S.; Albritton, Aaron; Konrad, Peter E.; Charles, David; Park, Sohee; Neimat, Joseph S.

    2015-01-01

    Parkinson’s disease (PD) is traditionally regarded as a neurodegenerative movement disorder, however, nigrostriatal dopaminergic degeneration is also thought to disrupt non-motor loops connecting basal ganglia to areas in frontal cortex involved in cognition and emotion processing. PD patients are impaired on tests of emotion recognition, but it is difficult to disentangle this deficit from the more general cognitive dysfunction that frequently accompanies disease progression. Testing for emotion recognition deficits early in the disease course, prior to cognitive decline, better assesses the sensitivity of these non-motor corticobasal ganglia-thalamocortical loops involved in emotion processing to early degenerative change in basal ganglia circuits. In addition, contrasting this with a group of healthy aging individuals demonstrates changes in emotion processing specific to the degeneration of basal ganglia circuitry in PD. Early PD patients (EPD) were recruited from a randomized clinical trial testing the safety and tolerability of deep brain stimulation (DBS) of the subthalamic nucleus (STN-DBS) in early-staged PD. EPD patients were previously randomized to receive optimal drug therapy only (ODT), or drug therapy plus STN-DBS (ODT + DBS). Matched healthy elderly controls (HEC) and young controls (HYC) also participated in this study. Participants completed two control tasks and three emotion recognition tests that varied in stimulus domain. EPD patients were impaired on all emotion recognition tasks compared to HEC. Neither therapy type (ODT or ODT + DBS) nor therapy state (ON/OFF) altered emotion recognition performance in this study. Finally, HEC were impaired on vocal emotion recognition relative to HYC, suggesting a decline related to healthy aging. This study supports the existence of impaired emotion recognition early in the PD course, implicating an early disruption of fronto-striatal loops mediating emotional function. PMID:25653616

  4. Prevalence and risk factors of contralateral extraprostatic extension in men undergoing radical prostatectomy for unilateral disease at biopsy: A global multi-institutional experience

    PubMed Central

    Bienz, Marc; Hueber, Pierre-Alain; Trudeau, Vincent; Alenizi, Abdullah M.; Valdivieso, Roger; Alom, Modar; Balbay, Mevlana Derya; Canda, Abdullah Erdem; Mouraviev, Vladimir; Albala, David M.; El-Hakim, Assaad; Trinh, Quoc-Dien; Latour, Mathieu; Saad, Fred; Zorn, Kevin C.

    2015-01-01

    Introduction: We assessed the incidence of contralateral prostate cancer (cPCa), contralateral EPE (cEPE) and contralateral positive surgical margins (cPSM) in patients diagnosed preoperatively with unilateral prostate cancer and evaluated risk factors predictive of contralateral disease extension. Methods: The occurrence of cPCa, cEPE and cPSM and the side-specific nerve-sparing technique performed were collected postoperatively from 327 men diagnosed with unilateral prostate cancer at biopsy. Parameters, such as the localization, proportion, and percentage of cancer in positive cores, were prospectively collected. Results: Overall, 50.5% of patients had bilateral disease, and were at higher risk when associated with a positive biopsy core at the apex (p = 0.016). The overall incidence of ipsilateral EPE and cEPE were 21.4% and 3.4%, respectively (p < 0.001). Compared to cPCa, ipsilateral disease was at an almost 4-fold higher risk of extending out of the prostate (p < 0.001). None of the criteria tested were identified as useful predictors for cEPE. The low incidence of cEPE in our cohort could limit our ability to detect significance. The overall incidence of ipsilateral PSM and cPSM were 15.3% and 5.8%, respectively (p < 0.001). More aggressive nerve-sparing was not associated with a higher incidence of PSM. Prostate sides selected for more aggressive nerve-sparing were associated with younger patients (p < 0.001), a smaller prostate (p = 0.006), and a lower percentage of cancer in biopsy material (p = 0.008). Conclusion: Although the risk of cPCa is high in patients diagnosed with unilateral prostate cancer at biopsy, the risk of cEPE and cPSM is low, yet not insignificant. Contralateral aggressive nerve-sparing should be used with caution and should not compromise oncological outcome. PMID:26279712

  5. Challenging complications of treatment – human herpes virus 6 encephalitis and pneumonitis in a patient undergoing autologous stem cell transplantation for relapsed Hodgkin's disease: a case report

    PubMed Central

    Bommer, Martin; Pauls, Sandra; Greiner, Jochen

    2009-01-01

    Background Reactivation of human herpesvirus 6 (HHV-6) occurs frequently in patients after allogeneic stem cell transplantation and is associated with bone-marrow suppression, enteritis, pneumonitis, pericarditis and also encephalitis. After autologous stem cell transplantation or intensive polychemotherapy HHV-6 reactivation is rarely reported. Case report This case demonstrates a severe symptomatic HHV-6 infection with encephalitis and pneumonitis after autologous stem cell transplantation of a patient with relapsed Hodgkin's disease. Conclusion Careful diagnostic work up in patients with severe complications after autologous stem cell transplantation is mandatory to identify uncommon infections. PMID:19619326

  6. Morpho-functional gastric pre-and post-operative changes in elderly patients undergoing laparoscopic cholecystectomy for gallstone related disease

    PubMed Central

    2012-01-01

    Background Cholecystectomy, gold standard treatment for gallbladder lithiasis, is closely associated with increased bile reflux into the stomach as amply demonstrated by experimental studies. The high prevalence of gallstones in the population and the consequent widespread use of surgical removal of the gallbladder require an assessment of the relationship between cholecystectomy and gastric mucosal disorders. Morphological evaluations performed on serial pre and post – surgical biopsies have provided new acquisitions about gastric damage induced by bile in the organ. Methods 62 elderly patients with gallstone related disease were recruited in a 30 months period. All patients were subjected to the most appropriate treatment (Laparoscopic cholecystectomy). The subjects had a pre-surgical evaluation with: • dyspeptic symptoms questionnaire, • gastric endoscopy with body, antrum, and fundus random biopsies, • histo-pathological analysis of samples and elaboration of bile reflux index (BRI). The same evaluation was repeated at a 6 months follow-up. Results In our series the duodeno-gastric reflux and the consensual biliary gastritis, assessed histologically with the BRI, was found in 58% of the patients after 6 months from cholecystectomy. The demonstrated bile reflux had no effect on H. pylori’s gastric colonization nor on the induction of gastric precancerous lesions. Conclusions Cholecystectomy, gold standard treatment for gallstone-related diseases, is practiced in a high percentage of patients with this condition. Such procedure, considered by many harmless, was, in our study, associated with a significant risk of developing biliary gastritis after 6 months during the postoperative period. PMID:23173777

  7. Hepatic Pathology Among Patients Without Known Liver Disease Undergoing Bariatric Surgery: Observations and a Perspective from the Longitudinal Assessment of Bariatric Surgery (LABS) Study

    PubMed Central

    Kleiner, David E.; Berk, Paul D.; Hsu, Jesse Y.; Courcoulas, Anita P.; Flum, David; Khandelwal, Saurabh; Pender, John; Pomp, Alfons; Roerig, James; Machado, Laura L.; Wolfe, Bruce M.; Belle, Steven H.

    2014-01-01

    Background Liver biopsy is not routine during bariatric surgery. Alanine aminotransferase (ALT) is widely used to screen for liver disease. We assessed the relationship between ALT and pathology in biopsies from Longitudinal Assessment of Bariatric Surgery (LABS) patients with normal preoperative ALTs. Methods Biopsies from the LABS-1 and LABS-2 studies were scored using the NASH CRN and Ishak systems. Diagnosis and histology were examined in relation to ALT. Results 693 suitable biopsies were evaluated. Biopsied patients had a median age of 45 years; 78.6% were female and 35.1% diabetic; median BMI was 46 kg/m2. 635 biopsied patients had preoperative ALTs. Median ALT was 25 IU/L, (IQR 19–36 IU/L); 26.6% had an ALT >35 IU/L and 29.9% exceeded the more restrictive Prati criteria for normal. Using the Prati criteria, 7.9% of participants with normal ALT had steatohepatitis and 5.3% had ≥stage 2 fibrosis. Logistic regression models were used to predict the probabilities of having bridging fibrosis/cirrhosis or a diagnosis of borderline/definite steatohepatitis in the unbiopsied LABS-2 sample. The proportion of biopsied participants with these findings was very similar to the modeled results from the unbiopsied cohorts. We estimated that 86.0% of participants with advanced fibrosis and 88.1% of participants with borderline/definite steatohepatitis were not biopsied and went undiagnosed. Conclusion As ALT did not reliably exclude significant obesity-related liver disease in bariatric surgery patients, consideration should be given to routine liver biopsy during bariatric surgery and medical follow-up of significant hepatic pathology. PMID:24782263

  8. Relationship between Fibroblast Growth Factor 23 and Biochemical and Bone Histomorphometric Alterations in a Chronic Kidney Disease Rat Model Undergoing Parathyroidectomy

    PubMed Central

    Liao, Hung-Wei; Hung, Peir-Haur; Hsiao, Chih-Yen; Liou, Hung-Hsiang; Lin, Hsin-Shih; Huang, Tsang-Hai; Jou, I-Ming; Tsai, Kuen-Jer

    2015-01-01

    Background Phosphate burden in chronic kidney disease (CKD) leads to elevated serum fibroblast factor-23 (FGF-23) levels, secondary hyperparathyroidism and chronic kidney disease-mineral bone disorder (CKD-MBD). However dissociated hyperphosphatemia and low serum FGF-23 concentrations have been observed in experimentally parathyoridectomized rats. The relationships between serum mineral, hormone, and bone metabolism may be altered in the presence of CKD. The aim of our study was to investigate whether a consistent relationship existed between serum FGF-23 levels, specific serum biochemical markers, and histomorphometric parameters of bone metabolism in a parathyroidectomized CKD animal model. Results Sprague Dawley rats were divided into 3 groups: parathyroidectomy (PTX) and CKD (PTX+CKD, 9 rats), CKD without PTX (CKD, 9 rats), and neither PTX nor CKD (sham-operated control, 8 rats); CKD was induced by partial nephrectomy. At 8 weeks after partial nephrectomy, serum biomarkers were measured. Bone histomorphometries of the distal femoral metaphyseal bone were analyzed. The mean serum FGF-23 levels and mean bone formation rate were the highest in the CKD group and the lowest in the PTX+CKD group. Bone volume parameters increased significantly in the PTX+CKD group. Pearson’s correlation revealed that serum FGF-23 levels associated with those of intact parathyroid hormone, phosphate, collagen type I C-telopeptide, and calcium. Univariate linear regression showed that serum FGF-23 values correlated with bone formation rate, bone volume, and osteoid parameters. Stepwise multivariate regression analysis revealed that circulating FGF-23 values were independently associated with bone volume and thickness (β = -0.737; p < 0.001 and β = -0.526; p = 0.006, respectively). Serum parathyroid hormone levels independently correlated with bone formation rate (β = 0.714; p < 0.001) while collagen type I C-telopeptide levels correlated with osteoid parameter. Conclusion Serum FGF

  9. Machado-Joseph Disease

    MedlinePlus

    ... for drunkenness, difficulty with speech and swallowing, impaired eye movements sometimes accompanied by double vision or bulging eyes, ... color and/or contrast, and inability to control eye movements. Some individuals also experience prominent Parkinson’s disease-like ...

  10. Evaluation of Four Risk-Scoring Methods to Predict Long-Term Outcomes in Patients Undergoing Aorto-Bifemoral Bypass for Aorto-Iliac Occlusive Disease

    PubMed Central

    García, Francisca; Marchena, Joaquín; Cabrera, Vicente; Hermida, María; Sotgiu, Enrico

    2012-01-01

    This study was done to determine the usefulness of the American Society of Anesthesiologists (ASA) classification, the comorbidity Charlson index unadjusted (CCIu),the comorbidity Charlson index adjusted by age (CCIa), and the Glasgow aneurysm score (GAS) for postoperative morbimortality and survival in patients treated with aorto-bifemoral bypass (AFB) for aorto-iliac occlusive disease (AIOD). A series of 278 patients who underwent AFB were restrospectively studied. For the CCIu, CCIa, ASA, and GAS, receiver operating characteristics curve analysis for prediction of morbidity showed area under the curves of 0.61 (p = 0.004), 0.59 (p = 0.026), 0.569 (p = 0.087), and 0.63 (p = 0.001), respectively. Additionally, univariate analysis showed that CCIa (p = 0.016) and GAS (p = 0.006) were associated significantly with an increased risk of developing complications. Furthermore, CCIa (p < 0.001) and GAS (p = 0.001) showed a significant association with survival. Finally, the variable age was related to morbidity (p = 0.004), mortality (p = 0.038), and survival (p < 0.001). The comorbididity and the age should be taken in account in clinical treatment decisions for patients with AIOD. The CCIa and GAS may play a role as predictive factors for postoperative morbidity and survival after AFB. PMID:23450270

  11. Beclomethasone Dipropionate in Preventing Acute Graft-Versus-Host Disease in Patients Undergoing a Donor Stem Cell Transplant for Hematologic Cancer

    ClinicalTrials.gov

    2015-03-05

    Hematopoietic/Lymphoid Cancer; Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Extramedullary Plasmacytoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Graft Versus Host Disease; Isolated Plasmacytoma of Bone; Juvenile Myelomonocytic Leukemia; Meningeal Chronic Myelogenous Leukemia; Myelodysplastic/Myeloproliferative Disease, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small

  12. Model-free causality analysis of cardiovascular variability detects the amelioration of autonomic control in Parkinson's disease patients undergoing mechanical stimulation.

    PubMed

    Bassani, Tito; Bari, Vlasta; Marchi, Andrea; Tassin, Stefano; Dalla Vecchia, Laura; Canesi, Margherita; Barbic, Franca; Furlan, Raffaello; Porta, Alberto

    2014-07-01

    We tested the hypothesis that causality analysis, applied to the spontaneous beat-to-beat variability of heart period (HP) and systolic arterial pressure (SAP), can identify the improvement of autonomic control linked to plantar mechanical stimulation in patients with Parkinson's disease (PD). A causality index, measuring the strength of the association from SAP to HP variability, and derived according to the Granger paradigm (i.e. SAP causes HP if the inclusion of SAP into the set of signals utilized to describe cardiovascular interactions improves the prediction of HP series), was calculated using both linear model-based (MB) and nonlinear model-free (MF) approaches. Univariate HP and SAP variability indices in time and frequency domains, and bivariate descriptors of the HP-SAP variability interactions were computed as well. We studied ten PD patients (age range: 57-78 years; Hoehn-Yahr scale: 2-3; six males, four females) without orthostatic hypotension or symptoms of orthostatic intolerance and 'on-time' according to their habitual pharmacological treatment. PD patients underwent recordings at rest in a supine position and during a head-up tilt before, and 24 h after, mechanical stimulation was applied to the plantar surface of both feet. The MF causality analysis indicated a greater involvement of baroreflex in regulating HP-SAP variability interactions after mechanical stimulation. Remarkably, MB causality and more traditional univariate or bivariate techniques could not detect changes in cardiovascular regulation after mechanical stimulation, thus stressing the importance of accounting for nonlinear dynamics in PD patients. Due to the higher statistical power of MF causality we suggest its exploitation to monitor the baroreflex control improvement in PD patients, and we encourage the clinical application of the Granger causality approach to evaluate the modification of the autonomic control in relation to the application of a pharmacological treatment, a

  13. Investigating Clinically Adequate Concentrations of Oseltamivir Carboxylate in End-Stage Renal Disease Patients Undergoing Hemodialysis Using a Population Pharmacokinetic Approach

    PubMed Central

    Lien, Kayla Yi Ting; Robson, Richard; Subramoney, Vishak; Clinch, Barry; Rayner, Craig R.; Gibiansky, Leonid

    2015-01-01

    End-stage renal disease (ESRD) patients receiving hemodialysis (HD) are at heightened risk for influenza, but the optimal oseltamivir dosage regimen for treating or preventing influenza in this high-risk population is still uncertain. Pharmacokinetic data for 24 adults with ESRD were pooled from a single-dose and a multiple-dose study to develop a population pharmacokinetic model using nonlinear mixed-effects modeling. The final model comprised five compartments, two each to describe the systemic pharmacokinetics of oseltamivir phosphate and its metabolite, oseltamivir carboxylate (OC), and a delay compartment to describe oseltamivir metabolism. Estimated OC clearance in the model was markedly faster during HD sessions (7.43 liters/min) than at other times (0.19 liter/min). Model simulations showed that 30 mg oseltamivir given after every HD session is the most suitable regimen for influenza treatment, producing trough OC concentrations above the median value achieved with the 75-mg twice-daily regimen in patients with normal renal function and peak concentrations below the highest oseltamivir exposures known to be well tolerated (median exposures after twice-daily dosing of 450 mg). Administration of the first dose following diagnosis of influenza need not wait until after the next HD session: addition of a single 30-mg dose during the 12 h before the next HD session raises OC exposures quickly without posing any safety risk. Further simulation showed that 30 mg oseltamivir given after every other HD session is the most suitable regimen for influenza prophylaxis. PMID:26282419

  14. Circulating miRNA panel for prediction of acute graft-versus-host disease in lymphoma patients undergoing matched unrelated hematopoietic stem cell transplantation.

    PubMed

    Gimondi, Silvia; Dugo, Matteo; Vendramin, Antonio; Bermema, Anisa; Biancon, Giulia; Cavané, Alessandra; Corradini, Paolo; Carniti, Cristiana

    2016-07-01

    Acute graft-versus-host disease (aGVHD) results in significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Noninvasive diagnostic and prognostic tests for aGVHD are currently lacking, but would be beneficial in predicting aGVHD and improving the safety of allo-HSCT. Circulating microRNAs exhibit marked stability and may serve as biomarkers in several clinical settings. Here, we evaluated the use of circulating microRNAs as predictive biomarkers of aGVHD in lymphoma patients after allo-HSCT from matched unrelated donors (MUDs). After receiving informed consent, we prospectively collected plasma samples from 24 lymphoma patients before and after unmanipulated MUD allo-HSCT; microRNAs were then isolated. Fourteen patients developed aGVHD symptoms at a median of 48 days (range: 32-90) post-transplantation. Two patients developed intestinal GVHD, eight cutaneous GVHD, and four multiorgan GVHD. The microRNA expression profile was examined using quantitative real-time polymerase chain reaction (qRT-PCR). MicroRNAs 194 and 518f were significantly upregulated in aGVHD samples compared with samples taken from non-aGVHD patients. Remarkably, these upregulated microRNAs could be detected before the onset of aGVHD. Pathway prediction analysis indicated that these microRNAs may regulate critical pathways involved in aGVHD pathogenesis. Considering the noninvasive characteristics of plasma sampling and the feasibility of detecting miRNAs after allo-HSCT using real-time polymerase chain reaction, our results indicate that circulating microRNAs have the potential to enable an earlier aGVHD diagnosis and might assist in individualizing therapeutic strategies after MUD allo-HSCT. Nevertheless, standardization of blood sampling and analysis protocols is mandatory for the introduction of miRNA profiling into routine clinical use. PMID:27013207

  15. 75 FR 9902 - Agency Forms Undergoing Paperwork Reduction Act Review

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  16. Asexual metazoans undergo senescence.

    PubMed

    Martínez, D E; Levinton, J S

    1992-10-15

    August Weismann popularized the notion that metazoans have a potentially immortal germ line separated from a mortal soma, and evolutionary biologists regard senescence as an evolved characteristic of the soma. Many have claimed that metazoans that do not sequester their germ line have no clear distinction between germ line and soma, and consequently they should lack senescence. Here we present experimental evidence that senescence occurs in the asexually reproducing marine oligochaete Paranais litoralis. We also analyze data reported in Sonneborn's classical study and show that the rhabdocoel Stenostomum incaudatum undergoes senescence. We argue that the stability of commitment to somatic function and the fact that asexual metazoans form their germ cells from undifferentiated stem cells are sufficient to allow for senescence of the asexual metazoan's soma. Thus the evolution of somatic differentiation, and not germ-line sequestration, would be the necessary condition for the evolution of senescence. PMID:11607334

  17. Recombinant Brain Natriuretic Peptide for the Prevention of Contrast-Induced Nephropathy in Patients with Chronic Kidney Disease Undergoing Nonemergent Percutaneous Coronary Intervention or Coronary Angiography: A Randomized Controlled Trial

    PubMed Central

    Liu, Jinming; Xie, Yanan; He, Fang; Gao, Zihan; Hao, Yuming; Zu, Xiuguang; Chang, Liang; Li, Yongjun

    2016-01-01

    The role of brain natriuretic peptide (BNP) in the prevention of contrast-induced nephropathy (CIN) is unknown. This study aimed to investigate BNP's effect on CIN in chronic kidney disease (CKD) patients undergoing elective percutaneous coronary intervention (PCI) or coronary angiography (CAG). The patients were randomized to BNP (0.005 μg/kg/min before contrast media (CM) exposure and saline hydration, n = 106) or saline hydration alone (n = 103). Cystatin C, serum creatinine (SCr) levels, and estimated glomerular filtration rates (eGFR) were assessed at several time points. The primary endpoint was CIN incidence; secondary endpoint included changes in cystatin C, SCr, and eGFR. CIN incidence was significantly lower in the BNP group compared to controls (6.6% versus 16.5%, P = 0.025). In addition, a more significant deterioration of eGFR, cystatin C, and SCr from 48 h to 1 week (P < 0.05) was observed in controls compared to the BNP group. Although eGFR gradually deteriorated in both groups, a faster recovery was achieved in the BNP group. Multivariate logistic regression revealed that using >100 mL of CM (odds ratio: 4.36, P = 0.004) and BNP administration (odds ratio: 0.21, P = 0.006) were independently associated with CIN. Combined with hydration, exogenous BNP administration before CM effectively decreases CIN incidence in CKD patients. PMID:26949703

  18. 78 FR 15368 - Agency Forms Undergoing Paperwork Reduction Act Review

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  1. 76 FR 78262 - Agency Forms Undergoing Paperwork Reduction Act Review

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    ... will provide estimates of behavior related to the risk of HIV and other sexually transmitted diseases... HUMAN SERVICES Centers for Disease Control and Prevention Agency Forms Undergoing Paperwork Reduction Act Review The Centers for Disease Control and Prevention (CDC) publishes a list of...

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    2011-03-07

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  5. 75 FR 67366 - Agency Forms Undergoing Paperwork Reduction Act Review

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  6. 76 FR 45256 - Agency Forms Undergoing Paperwork Reduction Act Review

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  8. Cardiovascular risk and mortality in end-stage renal disease patients undergoing dialysis: sleep study, pulmonary function, respiratory mechanics, upper airway collapsibility, autonomic nervous activity, depression, anxiety, stress and quality of life: a prospective, double blind, randomized controlled clinical trial

    PubMed Central

    2013-01-01

    Background Chronic kidney disease (CKD) is one of the most serious public health problems. The increasing prevalence of CKD in developed and developing countries has led to a global epidemic. The hypothesis proposed is that patients undergoing dialysis would experience a marked negative influence on physiological variables of sleep and autonomic nervous system activity, compromising quality of life. Methods/Design A prospective, consecutive, double blind, randomized controlled clinical trial is proposed to address the effect of dialysis on sleep, pulmonary function, respiratory mechanics, upper airway collapsibility, autonomic nervous activity, depression, anxiety, stress and quality of life in patients with CKD. The measurement protocol will include body weight (kg); height (cm); body mass index calculated as weight/height2; circumferences (cm) of the neck, waist, and hip; heart and respiratory rates; blood pressures; Mallampati index; tonsil index; heart rate variability; maximum ventilatory pressures; negative expiratory pressure test, and polysomnography (sleep study), as well as the administration of specific questionnaires addressing sleep apnea, excessive daytime sleepiness, depression, anxiety, stress, and quality of life. Discussion CKD is a major public health problem worldwide, and its incidence has increased in part by the increased life expectancy and increasing number of cases of diabetes mellitus and hypertension. Sleep disorders are common in patients with renal insufficiency. Our hypothesis is that the weather weight gain due to volume overload observed during interdialytic period will influence the degree of collapsibility of the upper airway due to narrowing and predispose to upper airway occlusion during sleep, and to investigate the negative influences of haemodialysis in the physiological variables of sleep, and autonomic nervous system, and respiratory mechanics and thereby compromise the quality of life of patients. Trial registration The

  9. Factors affecting postoperative blood loss in children undergoing cardiac surgery.

    PubMed

    Faraoni, David; Van der Linden, Philippe

    2014-01-01

    We hypothesized that the influence of cyanotic disease on postoperative blood loss is closely related to age in children undergoing cardiac surgery. Here, we demonstrate that the presence of a cyanotic disease is associated with increased postoperative blood loss in children aged 1 to 6 months. Children with cyanotic disease and aged<1 month who received fresh frozen plasma during cardiopulmonary bypass had less postoperative blood loss and higher maximal clot firmness on FIBTEM than cyanotic children from all other groups. Additional studies are needed to define optimal pathophysiology-based management in children undergoing cardiac surgery. PMID:24512988

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