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Sample records for disease undergo disease-like

  1. Genetics Home Reference: Huntington disease-like syndrome

    MedlinePlus

    ... Twitter Home Health Conditions Huntington disease-like syndrome Huntington disease-like syndrome Printable PDF Open All Close ... collapse boxes. Description As its name suggests, a Huntington disease -like (HDL) syndrome is a condition that ...

  2. Huntington's disease and Huntington's disease-like syndromes: an overview.

    PubMed

    Gövert, Felix; Schneider, Susanne A

    2013-08-01

    The differential diagnosis of chorea syndromes may be complex and includes various genetic disorders such as Huntington's disease and mimicking disorders called Huntington's disease-like (HDL) phenotypes. To familiarize clinicians with these (in some cases very rare) conditions we will summarize the main characteristics. HDL disorders are rare and account for about 1% of cases presenting with a Huntington's disease phenotype. They share overlapping clinical features, so making the diagnosis purely on clinical grounds may be challenging, however presence of certain characteristics may be a clue (e.g. prominent orofacial involvement in neuroferritinopathy etc.), Information of ethnic descent will also guide genetic work-up [HDL2 in Black Africans; dentatorubral-pallidoluysian atrophy (DRPLA) in Japanese etc.], Huntington's disease, the classical HDL disorders (except HDL3) and DRPLA are repeat disorders with anticipation effect and age-dependent phenotype in some, but genetic underpinnings may be more complicated in the other chorea syndromes. With advances in genetics more and more rare diseases are disentangled, allowing molecular diagnoses in a growing number of choreic patients. Hopefully, with better understanding of their pathophysiology we are moving towards mechanistic therapies.

  3. Memantine Attenuates Alzheimer's Disease-Like Pathology and Cognitive Impairment.

    PubMed

    Wang, Xiaochuan; Blanchard, Julie; Grundke-Iqbal, Inge; 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.

  4. Prion Disease Induces Alzheimer Disease-Like Neuropathologic Changes.

    PubMed

    Tousseyn, Thomas; Bajsarowicz, Krystyna; Sánchez, Henry; Gheyara, Ania; Oehler, Abby; Geschwind, Michael; DeArmond, Bernadette; DeArmond, Stephen J

    2015-09-01

    We examined the brains of 266 patients with prion disease (PrionD) and found that 46 patients (17%) had Alzheimer disease (AD)-like changes. To explore potential mechanistic links between PrionD and AD, we exposed human brain aggregates (BrnAggs) to a brain homogenate from a patient with sporadic Creutzfeldt-Jakob disease and found that neurons in human BrnAggs produced many β-amyloid (Aβ; Aβ42) inclusions, whereas uninfected control-exposed human BrnAggs did not. Western blot analysis of 20 pooled Creutzfeldt-Jakob disease-infected BrnAggs verified Aβ42 levels higher than those in controls. We next examined the CA1 region of the hippocampus from 14 patients with PrionD and found that 5 patients had low levels of scrapie-associated prion protein (PrP), many Aβ42 intraneuronal inclusions, low apolipoprotein E-4 (APOE-4), and no significant nerve cell loss. Seven patients had high levels of PrP, low Aβ42, high APOE-4, and 40% nerve cell loss, suggesting that APOE-4 and PrP together cause neuron loss in PrionD. There were also increased levels of hyperphosphorylated tau protein (Hτ) and Hτ-positive neuropil threads and neuron bodies in both PrionD and AD groups. The brains of 6 age-matched control patients without dementia did not contain Aβ42 deposits; however, there were rare Hτ-positive threads in 5 controls, and 2 controls had few Hτ-positive nerve cell bodies. We conclude that PrionD may trigger biochemical changes similar to those triggered by AD and suggest that PrionD is a disease involving PrP, Aβ42, APOE-4, and abnormal tau.

  5. Prion Disease Induces Alzheimer Disease-Like Neuropathologic Changes

    PubMed Central

    Tousseyn, Thomas; Bajsarowicz, Krystyna; Sánchez, Henry; Gheyara, Ania; Oehler, Abby; Geschwind, Michael; DeArmond, Bernadette; DeArmond, Stephen J.

    2016-01-01

    We examined the brains of 266 patients with prion diseases (PrionD) and found that 46 (17%) had Alzheimer disease (AD)-like changes. To explore potential mechanistic links between PrionD and AD, we exposed human brain aggregates (Hu BrnAggs) to brain homogenate from a patient with sporadic Creutzfeldt-Jakob disease (CJD) and found that the neurons in the Hu BrnAggs produced many β-amyloid (β42) inclusions, whereas uninfected, control-exposed Hu BrnAggs did not. Western blots of 20-pooled CJD-infected BrnAggs verified higher Aβ42 levels than controls. We next examined the CA1 region of the hippocampus from 14 patients with PrionD and found that 5 patients had low levels of scrapie-associated prion protein (PrPSc), many Aβ42 intraneuronal inclusions, low APOE-4, and no significant nerve cell loss. Seven patients had high levels of PrPSc, low Aβ42, high APOE-4 and 40% nerve cell loss, suggesting that APOE-4 and PrPSc together cause neuron loss in PrionD. There were also increased levels of hyperphosphorylated tau protein (Hτ) and Hτ-positive neuropil threads and neuron bodies in both PrionD and AD groups. The brains of 6 age-matched control patients without dementia did not contain Aβ42 deposits; however, there were rare Hτ-positive threads in 5 controls and 2 controls had a few Hτ-positive nerve cell bodies. We conclude that PrionD may trigger biochemical changes similar to AD and suggest that PrionD are diseases of PrPSc, Aβ42, APOE-4 and abnormal tau. PMID:26226132

  6. Dyrk1 inhibition improves Alzheimer's disease-like pathology.

    PubMed

    Branca, Caterina; Shaw, Darren M; Belfiore, Ramona; Gokhale, Vijay; Shaw, Arthur Y; Foley, Christopher; Smith, Breland; Hulme, Christopher; Dunckley, Travis; Meechoovet, Bessie; Caccamo, Antonella; Oddo, Salvatore

    2017-10-01

    There is an urgent need for the development of new therapeutic strategies for Alzheimer's disease (AD). The dual-specificity tyrosine phosphorylation-regulated kinase-1A (Dyrk1a) is a protein kinase that phosphorylates the amyloid precursor protein (APP) and tau and thus represents a link between two key proteins involved in AD pathogenesis. Furthermore, Dyrk1a is upregulated in postmortem human brains, and high levels of Dyrk1a are associated with mental retardation. Here, we sought to determine the effects of Dyrk1 inhibition on AD-like pathology developed by 3xTg-AD mice, a widely used animal model of AD. We dosed 10-month-old 3xTg-AD and nontransgenic (NonTg) mice with a Dyrk1 inhibitor (Dyrk1-inh) or vehicle for eight weeks. During the last three weeks of treatment, we tested the mice in a battery of behavioral tests. The brains were then analyzed for the pathological markers of AD. We found that chronic Dyrk1 inhibition reversed cognitive deficits in 3xTg-AD mice. These effects were associated with a reduction in amyloid-β (Aβ) and tau pathology. Mechanistically, Dyrk1 inhibition reduced APP and insoluble tau phosphorylation. The reduction in APP phosphorylation increased its turnover and decreased Aβ levels. These results suggest that targeting Dyrk1 could represent a new viable therapeutic approach for AD. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  7. Graft-versus-host disease-like erythroderma: a manifestation of thymoma-associated multiorgan autoimmunity

    PubMed Central

    Warren, Shay; Nehal, Kishwer; Querfeld, Christiane; Wong, Richard; Huang, James; Pulitzer, Melissa

    2016-01-01

    Thymoma associated multiorgan autoimmunity is a rare paraneoplastic disorder, clinicopathologically similar to graft versus host disease, which is thought to be mediated by dysfunctional negative thymocyte selection and abnormally low levels of Tregs. We report a 50 year old Chinese women with a history of malignant thymoma and myasthenia gravis who developed graft versus host disease- like erythroderma after instituting chemotherapy and undergoing myasthenia crisis. Clinically her rash presented as erythematous scaly papules, which evolved to psoriasiform patches and plaques with foci of vitiligo. Histopathologically the biopsy showed a predominantly interface dermatitis with necrotic keratinocytes extending to the upper levels of the epidermis, and florid basket weave orthokeratosis. Clinical and laboratory work-up ruled out common inflammatory or infectious causes, eventually favoring the diagnosis of TAMA with GVHD-like erythroderma. Unfortunately, the patient underwent multi-organ compromise and death due to respiratory failure from myasthenia crisis. Patients with TAMA have a poor clinical outlook; rare successful treatments include high dose oral steroids and additional modalities including bone marrow transplant and chemotherapeutic or biologic agents. As the predominant findings are in the skin, dermatologists and dermatopathologists are in a unique position to enable the early diagnosis and treatment of this unusual disease. PMID:26509934

  8. Pathogenic insights from Huntington's disease-like 2 and other Huntington's disease genocopies.

    PubMed

    Margolis, Russell L; Rudnicki, Dobrila D

    2016-12-01

    Huntington's disease-like 2 (HDL2) is a rare, progressive, autosomal dominant neurodegenerative disorder that genetically, clinically, and pathologically closely resembles Huntington's disease. We review HDL2 pathogenic mechanisms and examine the implications of these mechanisms for Huntington's disease and related diseases. HDL2 is caused by a CTG/CAG repeat expansion in junctophilin-3. Available data from cell and animal models and human brain suggest that HDL2 is a complex disease in which transcripts and proteins expressed bidirectionally from the junctophilin-3 locus contribute to pathogenesis through both gain-and loss-of-function mechanisms. Recent advances indicate that the pathogenesis of Huntington's disease is equally complex, despite the emphasis on toxic gain-of-function properties of the mutant huntingtin protein. Studies examining in parallel the genetic, clinical, neuropathological, and mechanistic similarities between Huntington's disease and HDL2 have begun to identify points of convergence between the pathogenic pathways of the two diseases. Comparisons to other diseases that are phenotypically or genetically related to Huntington's disease and HDL2 will likely reveal additional common pathways. The ultimate goal is to identify shared therapeutic targets and eventually develop therapies that may, at least in part, be effective across multiple similar rare diseases, an essential approach given the scarcity of resources for basic and translational research.

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

    PubMed

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

    2015-01-07

    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. 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. 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. 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. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  10. 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.

  11. 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

  12. Exploring the role of microorganisms in the disease-like syndrome affecting the sponge Ianthella basta.

    PubMed

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

    2010-09-01

    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.

  13. Adenyl cyclase activator forskolin protects against Huntington's disease-like neurodegenerative disorders

    PubMed Central

    Mehan, Sidharth; Parveen, Shaba; Kalra, Sanjeev

    2017-01-01

    Long term suppression of succinate dehydrogenase by selective inhibitor 3-nitropropionic acid has been used in rodents to model Huntington's disease where mitochondrial dysfunction and oxidative damages are primary pathological hallmarks for neuronal damage. Improvements in learning and memory abilities, recovery of energy levels, and reduction of excitotoxicity damage can be achieved through activation of Adenyl cyclase enzyme by a specific phytochemical forskolin. In this study, intraperitoneal administration of 10 mg/kg 3-nitropropionic acid for 15 days in rats notably reduced body weight, worsened motor cocordination (grip strength, beam crossing task, locomotor activity), resulted in learning and memory deficits, greatly increased acetylcholinesterase, lactate dehydrogenase, nitrite, and malondialdehyde levels, obviously decreased adenosine triphosphate, succinate dehydrogenase, superoxide dismutase, catalase, and reduced glutathione levels in the striatum, cortex and hippocampus. Intragastric administration of forskolin at 10, 20, 30 mg/kg dose-dependently reversed these behavioral, biochemical and pathological changes caused by 3-nitropropionic acid. These results suggest that forskolin exhibits neuroprotective effects on 3-nitropropionic acid-induced Huntington's disease-like neurodegeneration. PMID:28400813

  14. Beneficial effects of exercise in a transgenic mouse model of Alzheimer's disease-like Tau pathology.

    PubMed

    Belarbi, Karim; Burnouf, Sylvie; Fernandez-Gomez, Francisco-Jose; Laurent, Cyril; Lestavel, Sophie; Figeac, Martin; Sultan, Audrey; Troquier, Laetitia; Leboucher, Antoine; Caillierez, Raphaëlle; Grosjean, Marie-Eve; Demeyer, Dominique; Obriot, Hélène; Brion, Ingrid; Barbot, Bérangère; Galas, Marie-Christine; Staels, Bart; Humez, Sandrine; Sergeant, Nicolas; Schraen-Maschke, Susanna; Muhr-Tailleux, Anne; Hamdane, Malika; Buée, Luc; Blum, David

    2011-08-01

    Tau pathology is encountered in many neurodegenerative disorders known as tauopathies, including Alzheimer's disease. Physical activity is a lifestyle factor affecting processes crucial for memory and synaptic plasticity. Whether long-term voluntary exercise has an impact on Tau pathology and its pathophysiological consequences is currently unknown. To address this question, we investigated the effects of long-term voluntary exercise in the THY-Tau22 transgenic model of Alzheimer's disease-like Tau pathology, characterized by the progressive development of Tau pathology, cholinergic alterations and subsequent memory impairments. Three-month-old THY-Tau22 mice and wild-type littermates were assigned to standard housing or housing supplemented with a running wheel. After 9 months of exercise, mice were evaluated for memory performance and examined for hippocampal Tau pathology, cholinergic defects, inflammation and genes related to cholesterol metabolism. Exercise prevented memory alterations in THY-Tau22 mice. This was accompanied by a decrease in hippocampal Tau pathology and a prevention of the loss of expression of choline acetyltransferase within the medial septum. Whereas the expression of most cholesterol-related genes remained unchanged in the hippocampus of running THY-Tau22 mice, we observed a significant upregulation in mRNA levels of NPC1 and NPC2, genes involved in cholesterol trafficking from the lysosomes. Our data support the view that long-term voluntary physical exercise is an effective strategy capable of mitigating Tau pathology and its pathophysiological consequences.

  15. 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

  16. A Systematic Review of the Huntington Disease-Like 2 Phenotype.

    PubMed

    Anderson, David G; Walker, Ruth H; Connor, Myles; Carr, Jonathan; Margolis, Russell L; Krause, Amanda

    2017-01-01

    Huntington Disease-like 2 (HDL2) is a neurodegenerative disorder similar to Huntington Disease (HD) in its clinical phenotype, genetic characteristics, neuropathology and longitudinal progression. Proposed specific differences include an exclusive African ancestry, lack of eye movement abnormalities, increased Parkinsonism, and acanthocytes in HDL2. The objective was to determine the similarities and differences between HD and HDL2 by establishing the clinical phenotype of HDL2 with the published cases. A literature review of all clinically described cases of HDL2 until the end of 2016 was performed and a descriptive analysis was carried out. Sixty-nine new cases were described between 2001 and 2016. All cases had likely African ancestry, and most were found in South Africa and the USA. Many features were found to be similar to HD, including a strong negative correlation between repeat length and age of onset. Chorea was noted in 48/57 cases (84%). Dementia was reported in 74% patients, and Parkinsonism in 37%. Psychiatric features were reported in 44 out of 47 cases. Patients with chorea had lower expanded repeat lengths compared to patients without chorea. Eye movements were described in 19 cases, 8 were abnormal. Acanthocytes were detected in 4 of the 13 patients tested. Nineteen out of 20 MRIs were reported as abnormal with findings similar to HD. This review clarifies some aspects of the HDL2 phenotype and highlights others which require further investigation. Features that are unique to HDL2 have been documented in a minority of subjects and require prospective validation.

  17. The Frequency of Huntington Disease and Huntington Disease-Like 2 in the South African Population.

    PubMed

    Baine, Fiona K; Krause, Amanda; Greenberg, L Jacquie

    2016-01-01

    Huntington disease (HD) has most recently been estimated to affect between 10.6 and 13.7 per 100,000 individuals in European populations. However, prevalence is known to differ geographically. In South Africa, the only published estimates are from a survey performed in the 1970s, an era when the disease was believed to be rare or absent in black individuals and molecular confirmation was absent. The disease phenotype in South Africa is currently attributable to mutations in both the huntington and junctophilin-3 genes, which underlie the well-known HD and the rarer HD-like 2 (HDL2) respectively. This study aimed at providing improved minimum estimates of disease frequency in South Africa, based on molecular genetic testing data. A review of all testing records for HD and HDL2 over a 20-year period was undertaken. HDL2 is virtually indistinguishable on clinical features, thus necessitating its inclusion. Based on molecular diagnostic records, minimum estimates of disease frequency are: 5.1, 2.1 and 0.25 (per 100,000 individuals) for the white, mixed ancestry and black population groups respectively. Although ascertainment remains incomplete, these minimum estimates suggest that disease frequencies are significantly higher than those previously reported in South Africa. © 2016 S. Karger AG, Basel.

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

    PubMed Central

    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; Peles, Elior

    2015-01-01

    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

  19. Prevalence of Peyronie's Disease-Like Symptoms in Men Presenting With Dupuytren Contractures.

    PubMed

    Shindel, Alan W; Sweet, Genevieve; Thieu, William; Durbin-Johnson, Blythe; Rothschild, Jennifer; Szabo, Robert

    2017-09-01

    Peyronie's disease (PD) and Dupuytren contractures (DC) are often comorbid and are believed to have a similar underlying pathophysiologic mechanism. To investigate the prevalence of PD-like symptoms (PDLS) in men with DC. From October 2013 to December 2016, men who were seen and evaluated for DC were offered the opportunity to participate in an anonymous survey. The survey assessed several basic demographic and sexual health factors and included items from the International Index of Erectile Function and the Erection Hardness Scale. Men who reported PDLS were asked a series of questions derived from the Peyronie's Disease Questionnaire and for their opinions on theoretical treatment modalities for sexual problems and penile deformity. Prevalence of PDLS in men with DC. One hundred forty men with DC were invited to participate; 85 surveys were returned (response rate = 61%). Twenty-two respondents (26%, 95% confidence interval = 17-35) reported PDLS. Approximately one fourth of all respondents had an Erection Hardness Scale score lower than 3. The most common specific PDLS concerns were penile curvature (91%), length loss (55%), narrowing (36%), and hinging (32%). In men with PDLS, 73% felt at least a little bothered by the symptoms when attempting sexual activity and 40% reported having sex less frequently because of the symptoms. Just 27% of men with PDLS had ever used a treatment for a sexual concern. In terms of treatments for penile deformities, 64% of men with PDLS expressed an interest in treatment administered in the form of an in-office procedure; 41% were potentially amenable to a surgical procedure. The prevalence of PDLS in men with DC is similar to the prevalence of DC in men diagnosed with PD. A substantial number of these men have distress and would consider standard-of-care treatments for PD. Shindel AW, Sweet G, Thieu W, et al. Prevalence of Peyronie's Disease-Like Symptoms in Men Presenting With Dupuytren Contractures. Sex Med 2017;5:e135-e141

  20. Mucosal disease-like lesions in sheep infected with Border disease virus.

    PubMed

    Monies, R J; Paton, D J; Vilcek, S

    2004-12-11

    An enteric disease characterised by diarrhoea and ill thrift affected 12 of a flock of 700 six- to 12-month-old ewe lambs in Cornwall between December 1996 and September 1997. The affected lambs were undersized, became thin and suffered an unremitting diarrhoea until they died. The illness lasted for three to 14 days, although, with hindsight, the owner considered that the lambs had been below average size before the enteric signs developed. The outbreak ceased only as a result of the dispersal sale of the flock as breeding ewes. The flock had been purchased from different sources, but 11 of the cases occurred in a group of 40 purchased from one source. Postmortem, the alimentary changes resembled mucosal disease in cattle, and immunostaining of histological sections of the affected tissues revealed pestiviral antigen. Non-cytopathic pestiviruses were isolated from the lesions of two of the affected lambs and from the blood of several clinically normal ewe lambs from the same group. All the pestivirus isolates were typed as Border disease virus.

  1. 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

  2. Huntington disease and Huntington disease-like in a case series from Brazil.

    PubMed

    Castilhos, R M; Souza, A F D; Furtado, G V; Gheno, T C; Silva, A L; Vargas, F R; Lima, M-A F D; Barsottini, O; Pedroso, J L; Godeiro, C; Salarini, D; Pereira, E T; Lin, K; Toralles, M-B; Saute, J A M; Rieder, C R; Quintas, M; Sequeiros, J; Alonso, I; Saraiva-Pereira, M L; Jardim, L B

    2014-10-01

    The aim of this study was to identify the relative frequency of Huntington's disease (HD) and HD-like (HDL) disorders HDL1, HDL2, spinocerebellar ataxia type 2 (SCA2), SCA17, dentatorubral-pallidoluysian degeneration (DRPLA), benign hereditary chorea, neuroferritinopathy and chorea-acanthocytosis (CHAC), in a series of Brazilian families. Patients were recruited in seven centers if they or their relatives presented at least chorea, besides other findings. Molecular studies of HTT, ATXN2, TBP, ATN1, JPH3, FTL, NKX2-1/TITF1 and VPS13A genes were performed. A total of 104 families were ascertained from 2001 to 2012: 71 families from South, 25 from Southeast and 8 from Northeast Brazil. There were 93 HD, 4 HDL2 and 1 SCA2 families. Eleven of 104 index cases did not have a family history: 10 with HD. Clinical characteristics were similar between HD and non-HD cases. In HD, the median expanded (CAG)n (range) was 44 (40-81) units; R(2) between expanded HTT and age-at-onset (AO) was 0.55 (p=0.0001, Pearson). HDL2 was found in Rio de Janeiro (2 of 9 families) and Rio Grande do Sul states (2 of 68 families). We detected HD in 89.4%, HDL2 in 3.8% and SCA2 in 1% of 104 Brazilian families. There were no cases of HDL1, SCA17, DRPLA, neuroferritinopathy, benign hereditary chorea or CHAC. Only six families (5.8%) remained without diagnosis.

  3. periostin Null Mice Exhibit Dwarfism, Incisor Enamel Defects, and an Early-Onset Periodontal Disease-Like Phenotype

    PubMed Central

    Rios, Hector; Koushik, Shrinagesh V.; Wang, Haiyan; Wang, Jian; Zhou, Hong-Ming; Lindsley, Andrew; Rogers, Rhonda; Chen, Zhi; Maeda, Manabu; Kruzynska-Frejtag, Agnieszka; Feng, Jian Q.; Conway, Simon J.

    2005-01-01

    Periostin was originally identified as an osteoblast-specific factor and is highly expressed in the embryonic periosteum, cardiac valves, placenta, and periodontal ligament as well as in many adult cancerous tissues. To investigate its role during development, we generated mice that lack the periostin gene and replaced the translation start site and first exon with a lacZ reporter gene. Surprisingly, although periostin is widely expressed in many developing organs, periostin-deficient (perilacZ) embryos are grossly normal. Postnatally, however, ∼14% of the nulls die before weaning and all of the remaining perilacZ nulls are severely growth retarded. Skeletal analysis revealed that trabecular bone in adult homozygous skeletons was sparse, but overall bone growth was unaffected. Furthermore, by 3 months, the nulls develop an early-onset periodontal disease-like phenotype. Unexpectedly, these mice also show a severe incisor enamel defect, although there is no apparent change in ameloblast differentiation. Significantly, placing the perilacZ nulls on a soft diet that alleviated mechanical strain on the periodontal ligament resulted in a partial rescue of both the enamel and periodontal disease-like phenotypes. Combined, these data suggest that a healthy periodontal ligament is required for normal amelogenesis and that periostin is critically required for maintenance of the integrity of the periodontal ligament in response to mechanical stresses. PMID:16314533

  4. 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

  5. Maternal Genetic Mutations as Gestational and Early Life Influences in Producing Psychiatric Disease-Like Phenotypes in Mice

    PubMed Central

    Gleason, Georgia; Zupan, Bojana; Toth, Miklos

    2011-01-01

    Risk factors for psychiatric disorders have traditionally been classified as genetic or environmental. Risk (candidate) genes, although typically possessing small effects, represent a clear starting point to elucidate downstream cellular/molecular pathways of disease. Environmental effects, especially during development, can also lead to altered behavior and increased risk for disease. An important environmental factor is the mother, demonstrated by the negative effects elicited by maternal gestational stress and altered maternal care. These maternal effects can also have a genetic basis (e.g., maternal genetic variability and mutations). The focus of this review is “maternal genotype effects” that influence the emotional development of the offspring resulting in life-long psychiatric disease-like phenotypes. We have recently found that genetic inactivation of the serotonin 1A receptor (5-HT1AR) and the fmr1 gene (encoding the fragile X mental retardation protein) in mouse dams results in psychiatric disease-like phenotypes in their genetically unaffected offspring. 5-HT1AR deficiency in dams results in anxiety and increased stress responsiveness in their offspring. Offspring of 5-HT1AR deficient dams display altered development of the hippocampus, which could be linked to their anxiety-like phenotype. Maternal inactivation of fmr1, like its inactivation in the offspring, results in a hyperactivity-like condition and is associated with receptor alterations in the striatum. These data indicate a high sensitivity of the offspring to maternal mutations and suggest that maternal genotype effects can increase the impact of genetic risk factors in a population by increasing the risk of the genetically normal offspring as well as by enhancing the effects of offspring mutations. PMID:21629836

  6. 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

  7. Aluminium exposure induces Alzheimer's disease-like histopathological alterations in mouse brain.

    PubMed

    Rodella, L F; Ricci, F; Borsani, E; Stacchiotti, A; Foglio, E; Favero, G; Rezzani, R; Mariani, C; Bianchi, R

    2008-04-01

    Aluminium (Al) is a neurotoxic metal and Al exposure may be a factor in the aetiology of various neurodegenerative diseases such as Alzheimer's disease (AD). The major pathohistological findings in the AD brain are the presence of neuritic plaques containing beta-amyloid (Abeta) which may interfere with neuronal communication. Moreover, it has been observed that GRP78, a stress-response protein induced by conditions that adversely affect endoplasmic reticulum (ER) function, is reduced in the brain of AD patients. In this study, we investigated the correlation between the expression of Abeta and GRP78 in the brain cortex of mice chronically treated with aluminium sulphate. Chronic exposure over 12 months to aluminium sulphate in drinking water resulted in deposition of Abeta similar to that seen in congophilic amyloid angiopathy (CAA) in humans and a reduction in neuronal expression of GRP78 similar to what has previously been observed in Alzheimer's disease. So, we hypothesise that chronic Al administration is responsible for oxidative cell damage that interferes with ER functions inducing Abeta accumulation and neurodegenerative damage.

  8. Relationships between the Circadian System and Alzheimer's Disease-Like Symptoms in Drosophila

    PubMed Central

    Dutta, Sudeshna; Holbrook, Scott D.; Kotwica-Rolinska, Joanna; Kretzschmar, Doris; Giebultowicz, Jadwiga M.

    2014-01-01

    Circadian clocks coordinate physiological, neurological, and behavioral functions into circa 24 hour rhythms, and the molecular mechanisms underlying circadian clock oscillations are conserved from Drosophila to humans. Clock oscillations and clock-controlled rhythms are known to dampen during aging; additionally, genetic or environmental clock disruption leads to accelerated aging and increased susceptibility to age-related pathologies. Neurodegenerative diseases, such as Alzheimer's disease (AD), are associated with a decay of circadian rhythms, but it is not clear whether circadian disruption accelerates neuronal and motor decline associated with these diseases. To address this question, we utilized transgenic Drosophila expressing various Amyloid-β (Aβ) peptides, which are prone to form aggregates characteristic of AD pathology in humans. We compared development of AD-like symptoms in adult flies expressing Aβ peptides in the wild type background and in flies with clocks disrupted via a null mutation in the clock gene period (per01). No significant differences were observed in longevity, climbing ability and brain neurodegeneration levels between control and clock-deficient flies, suggesting that loss of clock function does not exacerbate pathogenicity caused by human-derived Aβ peptides in flies. However, AD-like pathologies affected the circadian system in aging flies. We report that rest/activity rhythms were impaired in an age-dependent manner. Flies expressing the highly pathogenic arctic Aβ peptide showed a dramatic degradation of these rhythms in tune with their reduced longevity and impaired climbing ability. At the same time, the central pacemaker remained intact in these flies providing evidence that expression of Aβ peptides causes rhythm degradation downstream from the central clock mechanism. PMID:25171136

  9. Tauroursodeoxycholic acid protects bile acid homeostasis under inflammatory conditions and dampens Crohn's disease-like ileitis.

    PubMed

    Van den Bossche, Lien; Borsboom, Daniel; Devriese, Sarah; Van Welden, Sophie; Holvoet, Tom; Devisscher, Lindsey; Hindryckx, Pieter; De Vos, Martine; Laukens, Debby

    2017-02-06

    Bile acids regulate the expression of intestinal bile acid transporters and are natural ligands for nuclear receptors controlling inflammation. Accumulating evidence suggests that signaling through these receptors is impaired in inflammatory bowel disease. We investigated whether tauroursodeoxycholic acid (TUDCA), a secondary bile acid with cytoprotective properties, regulates ileal nuclear receptor and bile acid transporter expression and assessed its therapeutic potential in an experimental model of Crohn's disease (CD). Gene expression of the nuclear receptors farnesoid X receptor, pregnane X receptor and vitamin D receptor and the bile acid transporters apical sodium-dependent bile acid transporter and organic solute transporter α and β was analyzed in Caco-2 cell monolayers exposed to tumor necrosis factor (TNF)α, in ileal tissue of TNF(ΔARE/WT) mice and in inflamed ileal biopsies from CD patients by quantitative real-time polymerase chain reaction. TNF(ΔARE/WT) mice and wild-type littermates were treated with TUDCA or placebo for 11 weeks and ileal histopathology and expression of the aforementioned genes were determined. Exposing Caco-2 cell monolayers to TNFα impaired the mRNA expression of nuclear receptors and bile acid transporters, whereas co-incubation with TUDCA antagonized their downregulation. TNF(ΔARE/WT) mice displayed altered ileal bile acid homeostasis that mimicked the situation in human CD ileitis. Administration of TUDCA attenuated ileitis and alleviated the downregulation of nuclear receptors and bile acid transporters in these mice. These results show that TUDCA protects bile acid homeostasis under inflammatory conditions and suppresses CD-like ileitis. Together with previous observations showing similar efficacy in experimental colitis, we conclude that TUDCA could be a promising therapeutic agent for inflammatory bowel disease, warranting a clinical trial.Laboratory Investigation advance online publication, 6 February 2017; doi:10

  10. The differential diagnosis of Huntington's disease-like syndromes: 'red flags' for the clinician.

    PubMed

    Martino, Davide; Stamelou, Maria; Bhatia, Kailash P

    2013-06-01

    A growing number of progressive heredodegenerative conditions mimic the presentation of Huntington's disease (HD). Differentiating among these HD-like syndromes is necessary when a patient with a combination of movement disorders, cognitive decline, behavioural abnormalities and progressive disease course proves negative to the genetic testing for HD causative mutations, that is, IT15 gene trinucleotide-repeat expansion. The differential diagnosis of HD-like syndromes is complex and may lead to unnecessary and costly investigations. We propose here a guide to this differential diagnosis focusing on a limited number of clinical features ('red flags') that can be identified through accurate clinical examination, collection of historical data and a few routine ancillary investigations. These features include the ethnic background of the patient, the involvement of the facio-bucco-lingual and cervical district by the movement disorder, the co-occurrence of cerebellar features and seizures, the presence of peculiar gait patterns and eye movement abnormalities, and an atypical progression of illness. Additional help may derive from the cognitive-behavioural presentation of the patient, as well as by a restricted number of ancillary investigations, mainly MRI and routine blood tests. These red flags should be constantly updated as the phenotypic characterisation and identification of more reliable diagnostic markers for HD-like syndromes progress over the following years.

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

    PubMed Central

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

    2016-01-01

    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

  12. Beneficial effects of caffeine in a transgenic model of Alzheimer's disease-like tau pathology.

    PubMed

    Laurent, Cyril; Eddarkaoui, Sabiha; Derisbourg, Maxime; Leboucher, Antoine; Demeyer, Dominique; Carrier, Sébastien; Schneider, Marion; Hamdane, Malika; Müller, Christa E; Buée, Luc; Blum, David

    2014-09-01

    Tau pathology found in Alzheimer's disease (AD) is crucial in cognitive decline. Epidemiologic evidences support that habitual caffeine intake prevents memory decline during aging and reduces the risk to develop Alzheimer's disease. So far, experimental studies addressed the impact of caffeine in models mimicking the amyloid pathology of AD. However, in vivo effects of caffeine in a model of AD-like tauopathy remain unknown. Here, we evaluated effects of chronic caffeine intake (0.3 g/L through drinking water), given at an early pathologic stage, in the THY-Tau22 transgenic mouse model of progressive AD-like tau pathology. We found that chronic caffeine intake prevents from the development of spatial memory deficits in tau mice. Improved memory was associated with reduced hippocampal tau phosphorylation and proteolytic fragments. Moreover, caffeine treatment mitigated several proinflammatory and oxidative stress markers found upregulated in the hippocampus of THY-Tau22 animals. Together, our data support that moderate caffeine intake is beneficial in a model of AD-like tau pathology, paving the way for future clinical evaluation in AD patients.

  13. 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

    2014-08-18

    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.

  14. 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.

  15. 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.

  16. The differential diagnosis of Huntington's disease-like syndromes: ‘red flags’ for the clinician

    PubMed Central

    Stamelou, Maria; Bhatia, Kailash P

    2013-01-01

    A growing number of progressive heredodegenerative conditions mimic the presentation of Huntington's disease (HD). Differentiating among these HD-like syndromes is necessary when a patient with a combination of movement disorders, cognitive decline, behavioural abnormalities and progressive disease course proves negative to the genetic testing for HD causative mutations, that is, IT15 gene trinucleotide-repeat expansion. The differential diagnosis of HD-like syndromes is complex and may lead to unnecessary and costly investigations. We propose here a guide to this differential diagnosis focusing on a limited number of clinical features (‘red flags’) that can be identified through accurate clinical examination, collection of historical data and a few routine ancillary investigations. These features include the ethnic background of the patient, the involvement of the facio-bucco-lingual and cervical district by the movement disorder, the co-occurrence of cerebellar features and seizures, the presence of peculiar gait patterns and eye movement abnormalities, and an atypical progression of illness. Additional help may derive from the cognitive–behavioural presentation of the patient, as well as by a restricted number of ancillary investigations, mainly MRI and routine blood tests. These red flags should be constantly updated as the phenotypic characterisation and identification of more reliable diagnostic markers for HD-like syndromes progress over the following years. PMID:22993450

  17. 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

  18. Chemotherapy improves thymoma-associated graft-versus-host-disease-like erythroderma.

    PubMed

    Nagano, Tatsuya; Kotani, Yoshikazu; Kobayashi, Kazuyuki; Tomita, Nanako; Nakata, Kyosuke; Sakashita, Akihiro; Funada, Yasuhiro; Nagai, Hiroshi; Itoh, Tomoo; Nishimura, Yoshihiro

    2011-05-10

    Graft-versus-host-disease (GVHD) with erythroderma can rarely occur in the context of thymoma and is associated with a poor prognosis due to an increased risk of infection-related death. The present study describes a case of a 50-year-old man with malignant thymoma who developed sepsis in addition to skin manifestations similar to that seen in GVHD. This patient experienced marked improvement in skin lesions in response to steroids and combination chemotherapy with carboplatin and paclitaxel, with subsequent resolution of infection. The present study describes the clinical course of this patient, followed by a review of pertinent reports of thymoma associated with GVHD with particular focus on the efficacy of treatment strategies.

  19. Capsaicin ameliorates stress-induced Alzheimer's disease-like pathological and cognitive impairments in rats.

    PubMed

    Jiang, Xia; Jia, Lin-Wei; Li, Xiao-Hong; Cheng, Xiang-Shu; Xie, Jia-Zhao; Ma, Zhi-Wei; Xu, Wei-Jie; Liu, Yue; Yao, Yun; Du, Lai-Ling; Zhou, Xin-Wen

    2013-01-01

    Hyperphosphorylated tau aggregated into neurofibrillary tangles is a hallmark lesion of Alzheimer's disease (AD) and is linked to synaptic and cognitive impairments. In animal models, cold water stress (CWS) can cause cognitive disorder and tau hyperphosphorylation. Capsaicin (CAP), a specific TRPV1 agonist, is neuroprotective against stress-induced impairment, but the detailed mechanisms are still elusive. Here, we investigated whether CAP mitigates CWS-induced cognitive and AD-like pathological alterations in rats. The animals were administered CAP (10 mg/kg in 0.2 ml, 0.1% ethanol) or a control (0.2 ml normal saline, 0.1% ethanol) by intragastric infusion 1 h before CWS treatment. Our results showed that CAP significantly attenuated CWS-induced spatial memory impairment and suppression of PP-DG long-term potentiation; CAP abolished CWS-induced dendritic regression and enhanced several memory-associated proteins decreased by CWS, such as synapsin I and PSD93; CAP also prevented CWS-induced tau hyperphosphorylation by abolishing inhibition of protein phosphatase 2A. Taken together, this study demonstrated that activation of TRPV1 can mitigate CWS-induced AD-like neuropathological alterations and cognitive impairment and may be a promising target for therapeutic intervention in AD.

  20. Loss of Polo ameliorates APP-induced Alzheimer's disease-like symptoms in Drosophila.

    PubMed

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

    2015-11-24

    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.

  1. 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

  2. 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

  3. Loss of presenilin function causes Alzheimer's disease-like neurodegeneration in the mouse.

    PubMed

    Chen, Qian; Nakajima, Akira; Choi, Se Hoon; Xiong, Xiaoli; Tang, Ya-Ping

    2008-05-15

    Accumulating evidence has indicated that gain-of-function in beta-amyloid production may be not the necessary mechanism for mutant presenilin-1 (PS1) or PS2 to cause familial Alzheimer's disease (AD). In the present article, we show that conditional knockout of PS1 from the adult stage in the forebrain of mice with the PS2 null mutation triggers robust AD-like neurodegeneration including brain shrinkage, cortical and hippocampal atrophy,ventricular enlargement, severe neuronal loss, gliosis, tau hyperphosphorylation, neurofillament tangle-like structures, and intracellular filaments. Learning and memory functions in these mice are almost completely lost. Notably, there is no beta-amyloid deposition, indicating that presenilin dysfunction can directly cause neurodegeneration without the involvement of beta-amyloid. Furthermore, neurodegeneration occurs in a progressive manner following aging, suggesting that an accumulating effect of presenilin dysfunction over time might be a pathogenic mechanism for the involvement of mutant PS1/PS2 in causing AD. These results validate a mouse model characterized by the presence of many features of AD pathology. Furthermore, the demonstration of AD-like neurodegeneration in the absence of beta-amyloid deposition challenges the long-standing beta-amyloid cascade hypothesis and encourages an open debate on the role of beta-amyloid in causing AD. Most important, our results strongly suggest that to develop gamma-secretase inhibitors for the pharmacological treatment of AD may be not a reasonable strategy because antagonism of presenilin function may worsen neurodegeneration.

  4. An antioxidant specifically targeting mitochondria delays progression of Alzheimer's disease-like pathology

    PubMed Central

    Stefanova, Natalia A.; Muraleva, Natalia A.; Maksimova, Kseniya Yi.; Rudnitskaya, Ekaterina A.; Kiseleva, Elena; Telegina, Darya V.; Kolosova, Nataliya

    2016-01-01

    Mitochondrial aberrations are observed in human Alzheimer's disease (AD) and in medical conditions that increase the risk of this disorder, suggesting that mitochondrial dysfunction may contribute to pathophysiology of AD. Here, using OXYS rats that simulate key characteristics of sporadic AD, we set out to determine the role of mitochondria in the pathophysiology of this disorder. OXYS rats were treated with a mitochondria-targeted antioxidant SkQ1 from age 12 to 18 months, that is, during active progression of AD-like pathology in these animals. Dietary supplementation with SkQ1 caused this compound to accumulate in various brain regions, and it was localized mostly to neuronal mitochondria. Via improvement of structural and functional state of mitochondria, treatment with SkQ1 alleviated the structural neurodegenerative alterations, prevented the neuronal loss and synaptic damage, increased the levels of synaptic proteins, enhanced neurotrophic supply, and decreased amyloid-β1-42 protein levels and tau hyperphosphorylation in the hippocampus of OXYS rats, resulting in improvement of the learning ability and memory. Collectively, these data support that mitochondrial dysfunction may play a key role in the pathophysiology of AD and that therapies with target mitochondria are potent to normalize a wide range of cellular signaling processes and therefore slow the progression of AD. PMID:27750209

  5. Huntington disease-like 2 (HDL2) in Venezuela: frequency and ethnic origin.

    PubMed

    Paradisi, Irene; Ikonomu, Vassiliki; Arias, Sergio

    2013-01-01

    Huntington disease (HD) phenotypes without a HTT mutation are known as HD-like (HDL) syndromes and are caused by mutations in other loci. HDL2, almost indistinguishable from HD, is due to expansions in the Junctophilin 3 locus (JPH3) with a worldwide Sub-Saharan ethnic origin. Sixteen independent patients with involuntary movements, psychiatric disturbances and ataxia not having a HTT mutation were searched for loci PRNP (prion protein, HDL1), JPH3 (HDL2), ATN1 (dentatorubral-pallidoluysian atrophy), ATX2 (spinocerebellar ataxia 2) ATXN3 (spinocerebellar ataxia 3), and TBP (spinocerebellar ataxia 17=HDL4). Markers Duffy, Kell, Diego, D9S1120, plus six JPH3 intragenic single-nucleotide polymorphisms were tested to ascertain ethnic origin. Four unrelated choreic patients had an expanded allele at JPH3. Three of them carried the African marker Duffy null. All four families carried with the mutation the same haplotype most frequent in African populations; Amerindian alleles D9D1120*9 and Diego A; or Kell allele K were absent. HDL2 in Venezuela had a low, but higher relative frequency (2.6%) than that in other Caucasoid populations. It should be searched first in choreic patients not having HTT mutations. The most likely remote ethnic origin for all detected families was African.

  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. 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

  8. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Description of Lyme disease-like syndrome in Brazil. Is it a new tick borne disease or Lyme disease variation?

    PubMed

    Mantovani, E; Costa, I P; Gauditano, G; Bonoldi, V L N; Higuchi, M L; Yoshinari, N H

    2007-04-01

    An emerging clinical entity that reproduces clinical manifestations similar to those observed in Lyme disease (LD) has been recently under discussion in Brazil. Due to etiological and laboratory particularities it is named LD-like syndrome or LD imitator syndrome. The condition is considered to be a zoonosis transmitted by ticks of the genus Amblyomma, possibly caused by interaction of multiple fastidious microorganisms originating a protean clinical picture, including neurological, osteoarticular and erythema migrans-like lesions. When peripheral blood of patients with LD-like syndrome is viewed under a dark-field microscope, mobile uncultivable spirochete-like bacteria are observed. PCR carried out with specific or conservative primers to recognize Borrelia burgdorferi sensu stricto or the genus Borrelia has been negative in ticks and in biological samples. Two different procedures, respectively involving hematoxylin and eosin staining of cerebrospinal fluid and electron microscopy analysis of blood, have revealed spirochetes not belonging to the genera Borrelia, Leptospira or Treponema. Surprisingly, co-infection with microorganisms resembling Mycoplasma and Chlamydia was observed on one occasion by electron microscopy analysis. We discuss here the possible existence of a new tick-borne disease in Brazil imitating LD, except for a higher frequency of recurrence episodes observed along prolonged clinical follow-up.

  10. 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.

  11. 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 Central

    Krause, A; Mitchell, CL; Essop, F; Tager, S; Temlett, J; Stevanin, G; Ross, CA; Rudnicki, DD; Margolis, RL

    2015-01-01

    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

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

    DOE PAGES

    Bauer, Ryan; Janowska, Katarzyna; Taylor, Kelly; ...

    2015-03-01

    Clostridium histolyticumcollagenases ColG and ColH are segmental enzymes that are thought to be activated by Ca2+-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 Ca2+-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 Ca2+-free apo s2a (1.8 Å resolution,R= 20.7%,Rfree= 27.2%) and twomore » 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 Ca2+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 Ca2+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 Ca2+binding. Conserved residues not only interact with Ca2+, but also position the Ca2+-interacting water molecule. Ca

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

    PubMed Central

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

    2015-01-01

    Clostridium histolyticum collagenases ColG and ColH are segmental enzymes that are thought to be activated by Ca2+-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 Ca2+-bound holo s2b (1.4 Å resolution, R = 15.0%, R free = 19.1%) and holo s2a (1.9 Å resolution, R = 16.3%, R free = 20.7%), as well as of Ca2+-free apo s2a (1.8 Å resolution, R = 20.7%, R free = 27.2%) and two new forms of N-terminally truncated apo s2 (1.4 Å resolution, R = 16.9%, R free = 21.2%; 1.6 Å resolution, R = 16.2%, R free = 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 Ca2+ 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 Ca2+ 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 Ca2+ binding. Conserved residues not only interact with Ca2+, but also position the Ca2

  14. 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

  15. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. 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

  17. mTOR in Down syndrome: Role in Aß and tau neuropathology and transition to Alzheimer disease-like dementia.

    PubMed

    Di Domenico, Fabio; Tramutola, Antonella; Foppoli, Cesira; Head, Elizabeth; Perluigi, Marzia; Butterfield, D Allan

    2017-08-12

    The mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase involved in the regulation of protein synthesis and degradation, longevity and cytoskeletal formation. The mTOR pathway represents a key growth and survival pathway involved in several diseases such as cancer, obesity, cardiovascular disease and neurodegenerative diseases. Numerous studies linked the alterations of mTOR pathway to age-dependent cognitive decline, pathogenesis of Alzheimer disease (AD) and AD-like dementia in Down syndrome (DS). DS is the most frequent chromosomal abnormality that causes intellectual disability. The neuropathology of AD in DS is complex and involves impaired mitochondrial function, defects in neurogenesis, increased oxidative stress, altered proteostasis and autophagy networks as a result of triplication of chromosome 21(chr 21). The chr21 gene products are considered a principal neuropathogenic moiety in DS. Several genes involved respectively in the formation of senile plaques and neurofibrillary tangles (NFT), two main pathological hallmarks of AD, are mapped on chr21. Further, in subjects with DS the activation of mTOR signaling contributes to Aβ generation and the formation of NFT. This review discusses recent research highlighting the complex role of mTOR associated with the presence of two hallmarks of AD pathology, senile plaques (composed mostly of fibrillar Aß peptides), and NFT (composed mostly of hyperphosphorylated tau protein). Oxidative stress, associated with chr21-related Aβ and mitochondrial alterations, may significantly contribute to this linkage of mTOR to AD-like neuropathology in DS. Copyright © 2017. Published by Elsevier Inc.

  18. 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.

  19. Deficits in the Mitochondrial Enzyme α-Ketoglutarate Dehydrogenase Lead to Alzheimer’s Disease-like Calcium Dysregulation

    PubMed Central

    Gibson, Gary E.; Chen, Huan-Lian; Xu, Hui; Qiu, Linghua; Xu, Zuoshang; Denton, Travis T.; Shi, Qingli

    2011-01-01

    Understanding the molecular sequence of events that culminate in multiple abnormalities in brains from patients that died with Alzheimer’s Disease (AD) will help to reveal the mechanisms of the disease and identify upstream events as therapeutic targets. The activity of the mitochondrial α-ketoglutarate dehydrogenase complex (KGDHC) in homogenates from autopsy brain declines with AD. Experimental reductions in KGDHC in mouse models of AD promote plaque and tangle formation, the hallmark pathologies of AD. We hypothesize that deficits in KGDHC also lead to the abnormalities in endoplasmic reticulum (ER) calcium stores and cytosolic calcium following K+ -depolarization that occur in cells from AD patients and transgenic models of AD. The activity of the mitochondrial enzyme KGDHC was diminished acutely (minutes), long term (days) or chronically (weeks). Acute inhibition of KGDHC produced effects on calcium opposite to those in AD, while the chronic or long term inhibition of KGDHC mimicked the AD-related changes in calcium. Divergent changes in proteins released from the mitochondria that effect ER calcium channels may underlie the selective cellular consequences of acute versus longer term inhibition of KGDHC. The results suggest that the mitochondrial abnormalities in AD can be upstream of those in calcium. PMID:22169199

  20. Aspirin-triggered lipoxin A4 stimulates alternative activation of microglia and reduces Alzheimer disease-like pathology in mice.

    PubMed

    Medeiros, Rodrigo; Kitazawa, Masashi; Passos, Giselle F; Baglietto-Vargas, David; Cheng, David; Cribbs, David H; LaFerla, Frank M

    2013-05-01

    Microglia play an essential role in innate immunity, homeostasis, and neurotropic support in the central nervous system. In Alzheimer disease (AD), these cells may affect disease progression by modulating the buildup of β-amyloid (Aβ) or releasing proinflammatory cytokines and neurotoxic substances. Discovering agents capable of increasing Aβ uptake by phagocytic cells is of potential therapeutic interest for AD. Lipoxin A4 (LXA4) is an endogenous lipid mediator with potent anti-inflammatory properties directly involved in inflammatory resolution, an active process essential for appropriate host responses, tissue protection, and the return to homeostasis. Herein, we demonstrate that aspirin-triggered LXA4 (15 μg/kg) s.c., twice a day, reduced NF-κB activation and levels of proinflammatory cytokines and chemokines, as well as increased levels of anti-inflammatory IL-10 and transforming growth factor-β. Such changes in the cerebral milieu resulted in recruitment of microglia in an alternative phenotype, as characterized by the up-regulation of YM1 and arginase-1 and the down-regulation of inducible nitric oxide synthase expression. Microglia in an alternative phenotype-positive cells demonstrated improved phagocytic function, promoting clearance of Aβ deposits and ultimately leading to reduction in synaptotoxicity and improvement in cognition. Our data indicate that activating LXA4 signaling may represent a novel therapeutic approach for AD. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  1. Intranasal BMP9 Ameliorates Alzheimer Disease-Like Pathology and Cognitive Deficits in APP/PS1 Transgenic Mice

    PubMed Central

    Wang, Zigao; Xiong, Lu; Wan, Wenbin; Duan, Lijie; Bai, Xiaojing; Zu, Hengbing

    2017-01-01

    Alzheimer’s disease (AD) is the most common type of dementia and has no effective therapies. Previous studies showed that bone morphogenetic protein 9 (BMP9), an important factor in the differentiation and phenotype maintenance of cholinergic neurons, ameliorated the cholinergic defects resulting from amyloid deposition. These findings suggest that BMP9 has potential as a therapeutic agent for AD. However, the effects of BMP9 on cognitive function in AD and its underlying mechanisms remain elusive. In the present study, BMP9 was delivered intranasally to 7-month-old APP/PS1 mice for 4 weeks. Our data showed that intranasal BMP9 administration significantly improved the spatial and associative learning and memory of APP/PS1 mice. We also found that intranasal BMP9 administration significantly reduced the amyloid β (Aβ) plaques overall, inhibited tau hyperphosphorylation, and suppressed neuroinflammation in the transgenic mouse brain. Furthermore, intranasal BMP9 administration significantly promoted the expression of low-density lipoprotein receptor-related protein 1 (LRP1), an important membrane receptor involved in the clearance of amyloid β via the blood-brain barrier (BBB), and elevated the phosphorylation levels of glycogen synthase kinase-3β (Ser9), which is considered the main kinase involved in tau hyperphosphorylation. Our results suggest that BMP9 may be a promising candidate for treating AD by targeting multiple key pathways in the disease pathogenesis. PMID:28228716

  2. Ammonium chloride and tunicamycin are novel toxins for dopaminergic neurons and induce Parkinson's disease-like phenotypes in medaka fish.

    PubMed

    Matsui, Hideaki; Ito, Hidefumi; Taniguchi, Yoshihito; Takeda, Shunichi; Takahashi, Ryosuke

    2010-12-01

    Perturbations in protein folding and degradation are key pathological mechanisms in neurodegenerative diseases, including Parkinson's disease (PD). Recent evidence suggests that mishandling of proteins may play an important role in the pathogenesis of PD. We have utilized medaka fish to monitor the effects of injecting neurotoxins into the CSF space. In this study, ammonium chloride, tunicamycin, and lactacystin were tested for their ability to disturb lysosomal proteolysis, N-glycosylation in the endoplasmic reticulum, and proteasomal degradation, respectively. All of the substances tested induced selective loss of dopaminergic neurons, movement disorders and inclusion bodies. Among them, the features of the inclusion bodies that developed after ammonium chloride injection mimicked those of PD: co-localization of ubiquitin and phosphorylated α-synuclein, as well as the presence of LC3 protein in the inclusion bodies. Our study demonstrated that medaka fish are useful for examining the effects of environmental toxins and lysosome inhibition, and lysosome inhibitors may be factors in the development of PD.

  3. Immunoproteasome deficiency alters microglial cytokine response and improves cognitive deficits in Alzheimer's disease-like APPPS1 mice.

    PubMed

    Wagner, Lisa K; Gilling, Kate E; Schormann, Eileen; Kloetzel, Peter M; Heppner, Frank L; Krüger, Elke; Prokop, Stefan

    2017-06-24

    The immunoproteasome (iP) represents a specialized type of proteasomes, which plays an important role in the clearance of oxidant-damaged proteins under inflammatory and pathological conditions determining the outcome of various diseases. In Alzheimer's disease (AD)-like APPPS1 mice Aβ-deposition is paralleled by iP upregulation, most likely mediated through type I interferon induction. To define the impact of increased iP expression we crossed APPPS1 mice with mice deficient in the iP subunit LMP7 resulting in impaired iP function. While LMP7 deficient APPPS1 mice showed no major change in cerebral Aβ-pathology, we observed an altered cytokine response in microglia isolated from LMP7 deficient APPPS1 mice compared to LMP7 expressing APPPS1 control mice. The altered microglial cytokine profile upon iP deficiency in the presence of extracellular Aβ-pathology was associated with an improvement of Aβ-associated cognitive deficits typically present in APPPS1 mice. Our findings suggest a role for iP in the regulation of the innate immune response towards extracellular Aβ-pathology and indicate that inhibition of iP function can modulate the cognitive phenotype upon overexpression of Aβ.

  4. 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

  5. Adult-onset Still's disease-like manifestation accompanied by the cancer recurrence after long-term resting state.

    PubMed

    Fukuoka, Kazuhito; Miyamoto, Ayako; Ozawa, Yuko; Ikegaya, Noriko; Maesono, Tomohiro; Komagata, Yoshinori; Kaname, Shinya; Arimura, Yoshihiro

    2016-12-09

    A 72-year-old woman presented 9 months ago with skin rash on her bilateral forearms, which was followed by intermittent high fever, and stiffness and swelling of her bilateral fingers. She was diagnosed with seronegative rheumatoid arthritis (RA). She had a past history of breast cancer and had undergone breast preservation surgery 13 years previously. During admission in our hospital, she developed high fever and leukocytosis with a relapsing skin rash, sore throat, polyarthralgia and increased levels of serum ALT/AST and ferritin, all of which fulfilled Yamaguchi's criteria for adult-onset Still's disease (AOSD). While we tried to exclude other diseases that may show AOSD-like manifestations, pancytopenia rapidly developed and bone marrow biopsy strongly suggested the diagnosis of macrophage activating syndrome (MAS). Accordingly, steroid pulse therapy was begun, followed by oral glucocorticoid therapy. Thereafter, all of her symptoms improved, but systemic rash, inflammatory signs and pancytopenia gradually progressed. The results of bone marrow pathology, which returned 2 weeks after the beginning of treatment, revealed hemophagocytosis with CK7-positive/CK20-negative atypical cells that suggested recurrence of breast cancer in the bone marrow, thus all of her AOSD-like symptoms were considered to be paraneoplastic manifestations of late-onset metastatic breast cancer. She was treated successfully with chemotherapy. When we see the patients showing AOSD-like symptoms with a history of malignancy, we should consider the possibility of paraneoplastic syndrome due to cancer recurrence.

  6. Olive oil reduces oxidative damage in a 3-nitropropionic acid-induced Huntington's disease-like rat model.

    PubMed

    Tasset, I; Pontes, A J; Hinojosa, A J; de la Torre, R; Túnez, I

    2011-05-01

    Free radicals contribute to altered neuronal functions in neurodegenerative diseases and brain aging, by producing lipid- and other molecule-dependent modifications. The Mediterranean diet has been associated with a reduced risk of neurodegenerative disease. This study sought to verify whether extra-virgin olive oil (EVOO) exerted a brain antioxidant effect, protecting the brain against the oxidative stress caused by 3-nitropropionic acid (3NP). 3NP was administered intraperitoneally (i.p.) at a dose of 20 mg/kg body weight over four consecutive days. EVOO (representing 10% of calorie intake in the total standard daily diet of rats) and hydroxytyrosol (HT; 2.5 mg/kg body weight) were administered for 14 days. In all studied samples, 3NP caused a rise in lipid peroxides (LPO) and a reduction in glutathione (GSH) content. While the results showed that EVOO and HT reduces lipid peroxidation product levels and blocks the GSH depletion prompted by 3NP in both striatum and rest of the brain in Wistar rats. In addition, EVOO blocks and reverses the effect of 3NP on succinate dehydrogenase activity. In brief, the data obtained indicate that EVOO and HT act as a powerful brain antioxidant.

  7. 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

  8. Glio-vascular changes during ageing in wild-type and Alzheimer's disease-like APP/PS1 mice.

    PubMed

    Janota, C S; Brites, D; Lemere, C A; Brito, M A

    2015-09-16

    Vascular and glial involvement in the development of neurodegenerative disorders, such as Alzheimer's disease (AD), and age-related brain vulnerabilities have been suggested. Therefore, we sought to: (i) investigate which vascular and glial events are evident in ageing and/or AD, (ii) to establish the temporal evolution of vascular and glial changes in AD-like and wild-type (WT) mice and (iii) to relate them to amyloid-β (Aβ) peptide accumulation. We examined immunohistochemically hippocampi and cortex from APP/PS1dE9 and WT C57BL/6 mice along ageing and disease progression (young-adulthood, middle- and old-age). Ageing resulted in the increase in receptor for advanced glycation endproducts expression, as well as the entrance of thrombin and albumin in hippocampal parenchyma. In contrast, the loss of platelet-derived growth factor receptor-β (PDGFR-β) positive cells, in both regions, was only related to AD pathogenesis. Hypovascularization was affected by both ageing and AD in the hippocampus, but resulted from the interaction between both factors in the cortex. Astrogliosis was a result of AD in hippocampus and of both factors in cortex, while microgliosis was associated with fibrillar amyloid plaques in AD-like mice and with the interaction between both factors in each of the studied regions. In sum, these data show that senile plaques precede vascular and glial alterations only in hippocampus, whereas in cortex, vascular and glial alterations, namely the loss of PDGFR-β-positive cells and astrogliosis, accompanied the first senile plaques. Hence, this study points to vascular and glial events that co-exist in AD pathogenesis and age-related brain vulnerabilities.

  9. 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.

  10. 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

    2015-03-04

    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.

  11. 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

  12. Mass-forming primary angiitis of central nervous system with Rosai-Dorfmann disease-like massive histiocytosis with emperipolesis.

    PubMed

    Kim, Seong-Ik; Kim, Soo Hee; Cho, Hwa Jin; Kim, Hannah; Chung, Chun-Kee; Choi, Seung Hong; Park, Sung-Hye

    2015-08-01

    Primary angiitis of the central nervous system (PACNS) is a vasculitis restricted to the CNS without systemic involvement. We report a case of PACNS that was radiologically tumor-mimicking, and pathologically similar to the Rosai-Dorfmann disease. A 20-year-old woman presented with a focal facial motor seizure. Magnetic resonance image revealed heterogeneously enhanced well-demarcated solitary cerebral mass in the posterior frontal lobe. Histopathologically, the lesion showed lymphoplasmacytic vasculitis with massive parenchymal infiltration of large histiocytes with emperipolesis. Diffuse ischemic change, necrosis, hemorrhage of the brain parenchyma with neuronophagia, and extensive reactive gliosis by gemistocytic astrocytes were accompanying microscopic features. The patient was doing well for 3 years after complete resection of the lesion, except for occasional occurrence of alcohol- or sleep deprivation-associated seizure. We describe this unique case to provide evidence that mass formation can be developed in PACNS by accompanying parenchymal lymphohistiocytic infiltration, necrosis, and marked reactive gliosis. © 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

  13. Caffeine protects against oxidative stress and Alzheimer's disease-like pathology in rabbit hippocampus induced by cholesterol-enriched diet.

    PubMed

    Prasanthi, Jaya R P; Dasari, Bhanu; Marwarha, Gurdeep; Larson, Tyler; Chen, Xuesong; Geiger, Jonathan D; Ghribi, Othman

    2010-10-15

    Cholesterol has been linked to the pathogenesis of sporadic Alzheimer's disease (AD) as a risk factor increasing beta-amyloid (Abeta) and oxidative stress levels. Caffeine has antioxidant properties and has been demonstrated to reduce Abeta levels in transgenic mouse models of familial AD. However, the effects of caffeine on cholesterol-induced sporadic AD pathology have not been determined. In this study, we determined the effects of caffeine on Abeta levels, tau phosphorylation, oxidative stress generation, and caffeine-target receptors in rabbits fed a 2% cholesterol-enriched diet, a model system for sporadic AD. Our results showed that the cholesterol-enriched diet increased levels of Abeta, tau phosphorylation, and oxidative stress measured as increased levels of reactive oxygen species and isoprostanes, glutathione depletion, and increased levels of endoplasmic reticulum stress marker proteins. Additionally, the cholesterol-enriched diet reduced the levels of adenosine A(1) receptors (A(1)R) but not ryanodine or adenosine A(2A) receptors. Caffeine, administered at 0.5 and 30mg/day in the drinking water, reduced the cholesterol-induced increase in Abeta, phosphorylated tau, and oxidative stress levels and reversed the cholesterol-induced decrease in A(1)R levels. Our results suggest that even very low doses of caffeine might protect against sporadic AD-like pathology. Copyright 2010 Elsevier Inc. All rights reserved.

  14. Application of stable isotopic techniques in the prevention of degenerative diseases like obesity and NIDDM in developing societies.

    PubMed

    Shetty, Prakash; Iyengar, Venkatesh; Sawaya, Ana; Diaz, Erik; Ma, Guansheng; Hernandez-Triana, Manuel; Yajnik, Chittaranjan; Forrester, Terrence; Valencia, Mauro; Rush, Elaine; Adeyemo, Adebowale; Jahoor, Farook; Roberts, Susan

    2002-09-01

    Economic development in developing societies characterized by industrialization, urbanization, and globalization has seen the emergence of an epidemic of diet- and life-style-related chronic degenerative diseases. A research project was initiated under the aegis of the International Atomic Energy Agency (IAEA), Vienna, Austria under its Coordinated Research Programme (CRP) to promote the use of stable isotopic techniques to document the extent of the problem and to understand the determinants of this epidemic. The principal objectives of this CRP involving countries both in the North and the South are to define the magnitude of the problem of obesity and non-insulin dependent diabetes mellitus (NIDDM) in developing countries, to identify the vulnerable groups at increased risk, and to attempt to describe the metabolic and physiological mechanisms underlying this phenomenon. These comparative international studies of obesity and NIDDM are looking at the effects of childhood malnutrition (Brazil) and socioeconomic differentials (Mexico) on adult risk factors; the composition of the daily diet on obesity (Chile); levels of patterns of physical activity of older adults (China) as well as their influence on weight gain and obesity (Cuba, Nigeria); the impact of body composition and energy expenditure on the evolution frank diabetes from impaired glucose tolerance (Jamaica), and of body compositional changes and the role of inflammatory cytokines on impaired glucose tolerance (India). The last study conducted in New Zealand was aimed at comparing the energy expenditures of Maori (Pacific Island) with New Zealanders of European descent.

  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. Synergistical neuroprotection of rofecoxib and statins against malonic acid induced Huntington's disease like symptoms and related cognitive dysfunction in rats.

    PubMed

    Kumar, Anil; Sharma, Neha; Mishra, Jitendriya; Kalonia, Harikesh

    2013-06-05

    Malonic acid (MA) is a reversible inhibitor of succinate dehydrogenase (SDH) which induces mitochondrial dysfunction followed by secondary excitotoxicity and apoptosis due to generation of reactive oxygen species. Therapeutic potential of rofecoxib and statins have been well documented in several experimental models of neurodegenerative disorders, however, its exact mechanism of action is not known properly. Therefore, the present study is an attempt to investigate the effect of rofecoxib along with the statins against MA induced behavioural and biochemical alterations in rats. Single intrastriatal MA (6 µmol) significantly caused motor incordination, memory dysfunction and alteration in the antioxidant enzyme levels, mitochondrial enzyme complex (I, II, IV) activities, mitochondrial redox ratio and pro-inflammatory cytokine [tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] levels in the striatum as compared to the naive group. Fourteen days treatment with rofecoxib, atorvastatin, simvastatin significantly attenuated these behavioural, biochemical, and cellular alterations as compared to control (MA treated group). However, the treatment of rofecoxib along with atorvastatin or simvastatin significantly attenuated these behavioural, biochemical, and cellular alterations as compared to their individual effects. The results of the present study demonstrated that rofecoxib modulates the protective effects of statins against MA-induced neurobehavioral and related biochemical and cellular alterations in rats. This further provides evidence toward the involvement of neuroinflammatory cascade in the pathogenesis of Huntington's disease.

  17. 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

  18. Long-term prevention of Alzheimer's disease-like behavioral deficits in PDAPP mice carrying a mutation in Asp664.

    PubMed

    Galvan, Veronica; Zhang, Junli; Gorostiza, Olivia F; Banwait, Surita; Huang, Wei; Ataie, Marina; Tang, Huidong; Bredesen, Dale E

    2008-08-22

    The deficits of Alzheimer's disease (AD) are believed to result, at least in part, from neurotoxicity of beta-amyloid (Abeta), a set of 38-43 amino acid fragments derived from the beta-amyloid precursor protein (APP). In addition, APP generates the APP-C31 and Jcasp toxic fragments intracellularly by cleavage at Asp664. We reported that mutation of Asp664 to Ala in a FAD-human APP transgene prevented AD-like deficits but did not affect Abeta production or deposition in PDAPP mice, arguing that D664A plays a crucial role in the generation of AD-like deficits. Whether D664A simply delays or completely prevents AD-like deficits, however, remained undefined. To address this question, we performed behavioral studies longitudinally on a pretrained mouse cohort at 9 and 13 months (mo) of age. While behavioral deficits were present in PDAPP mice, performance of Tg PDAPP(D664A) mice was not significantly different from non-Tg littermates' across all ages tested. Moreover, aberrant patterns in non-cognitive components of behavior in PDAPP mice were ameliorated in PDAPP(D664A) animals as well. A trend towards poorer retention at 9 mo and poorer learning at 13 mo that did not reach statistical significance was observed in PDAPP(D664A) mice. These results support and extend recent studies showing that cleavage of APP at Asp664 (or protein-protein interactions dependent on Asp664) is a crucial event in the generation of AD-like deficits in PDAPP mice. Our results thus further demonstrate that the D664A mutation either completely precludes, or markedly delays (beyond 13 mo) the appearance of AD-like deficits in this mouse model of AD.

  19. Defective ATG16L1-mediated removal of IRE1α drives Crohn's disease-like ileitis.

    PubMed

    Tschurtschenthaler, Markus; Adolph, Timon E; Ashcroft, Jonathan W; Niederreiter, Lukas; Bharti, Richa; Saveljeva, Svetlana; Bhattacharyya, Joya; Flak, Magdalena B; Shih, David Q; Fuhler, Gwenny M; Parkes, Miles; Kohno, Kenji; Iwawaki, Takao; Janneke van der Woude, C; Harding, Heather P; Smith, Andrew M; Peppelenbosch, Maikel P; Targan, Stephan R; Ron, David; Rosenstiel, Philip; Blumberg, Richard S; Kaser, Arthur

    2017-02-01

    ATG16L1(T300A), a major risk polymorphism in Crohn's disease (CD), causes impaired autophagy, but it has remained unclear how this predisposes to CD. In this study, we report that mice with Atg16l1 deletion in intestinal epithelial cells (IECs) spontaneously develop transmural ileitis phenocopying ileal CD in an age-dependent manner, driven by the endoplasmic reticulum (ER) stress sensor IRE1α. IRE1α accumulates in Paneth cells of Atg16l1(ΔIEC) mice, and humans homozygous for ATG16L1(T300A) exhibit a corresponding increase of IRE1α in intestinal epithelial crypts. In contrast to a protective role of the IRE1β isoform, hyperactivated IRE1α also drives a similar ileitis developing earlier in life in Atg16l1;Xbp1(ΔIEC) mice, in which ER stress is induced by deletion of the unfolded protein response transcription factor XBP1. The selective autophagy receptor optineurin interacts with IRE1α, and optineurin deficiency amplifies IRE1α levels during ER stress. Furthermore, although dysbiosis of the ileal microbiota is present in Atg16l1;Xbp1(ΔIEC) mice as predicted from impaired Paneth cell antimicrobial function, such structural alteration of the microbiota does not trigger ileitis but, rather, aggravates dextran sodium sulfate-induced colitis. Hence, we conclude that defective autophagy in IECs may predispose to CD ileitis via impaired clearance of IRE1α aggregates during ER stress at this site. © 2017 Tschurtschenthaler et al.

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

    PubMed

    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.

  1. Impact of Changes in Neurotrophic Supplementation on Development of Alzheimer's Disease-Like Pathology in Oxys Rats.

    PubMed

    Rudnitskaya, E A; Kolosova, N G; Stefanova, N A

    2017-03-01

    Alzheimer's disease (AD) is the most common type of age-related dementia. The development of neurodegeneration in AD is closely related to alterations in neurotrophic supplementation of the brain, which may be caused either by disorder of neurotrophin metabolism or by modification of its availability due to changes in the microenvironment of neurons. The underlying mechanisms are not fully understood. In this work, we used senescence-accelerated OXYS rats as a unique model of the sporadic form of AD to examine the relationship of development of AD signs and changes in neurotrophic supplementation of the cortex. Based on comparative analysis of the transcriptome of the frontal cerebral cortex of OXYS and Wistar (control) rats, genes of a neurotrophin signaling pathway with different mRNA levels in the period prior to the development of AD-like pathology in OXYS rats (20 days) and in the period of its active manifestation (5 months) and progression (18 months) were identified. The most significant changes in mRNA levels in the cortex of OXYS rats occurred in the period from 5 to 18 months of age. These genes were associated with neurogenesis, neuronal differentiation, synaptic plasticity, and immune response. The results were compared to changes in the levels of brain-derived neurotrophic factor (BDNF), its receptors TrkB and p75(NTR), as well as with patterns of their colocalization, which reveal the balance of proneurotrophins and mature neurotrophins and their receptors. We found that alterations in neurotrophic balance indicating increased apoptosis precede the development of AD-like pathology in OXYS rats. Manifestation of AD-like pathology occurs against a background of activation of compensatory and regenerative processes including increased neurotrophic supplementation. Active progression of AD-like pathology in OXYS rats is accompanied by the suppression of activity of the neurotrophin system. Thus, the results confirm the importance of the neurotrophin

  2. A Novel Antisense CAG Repeat Transcript at JPH3 Locus Mediating Expanded Polyglutamine Protein Toxicity in Huntington’s Disease-Like 2 (HDL2) Mice

    PubMed Central

    Wilburn, Brian; Rudnicki, Dobrila D.; Zhao, Jing; Weitz, Tara Murphy; Cheng, Yin; Gu, Xiaofeng; Greiner, Erin; Park, Chang Sin; Wang, Nan; Sopher, Bryce L.; La Spada, Albert R.; Osmand, Alex; Margolis, Russell L.; Sun, Yi E.; Yang, X. William

    2011-01-01

    SUMMARY Huntington’s disease like-2 (HDL2) is a phenocopy of Huntington’s disease caused by CTG/CAG repeat expansion at the Junctophilin-3 (JPH3) locus. The mechanisms underlying HDL2 pathogenesis remain unclear. Here we developed a BAC transgenic mouse model of HDL2 (BAC-HDL2) that exhibits progressive motor deficits, selective neurodegenerative pathology and ubiquitin-positive nuclear inclusions (NIs). Molecular analyses reveal a novel promoter at the transgene locus driving the expression of a CAG repeat transcript (HDL2-CAG) from the strand antisense to JPH3, which encodes an expanded polyglutamine (polyQ) protein. Importantly, BAC-HDL2 but not control BAC mice accumulate polyQ-containing NIs in a pattern strikingly similar to those in the patients. Furthermore, BAC mice with genetic silencing of the expanded CUG transcript still express HDL2-CAG transcript and manifest polyQ pathogenesis. Finally, studies of HDL2 mice and patients revealed CBP sequestration into NIs and evidence for interference of CBP-mediated transcriptional activation. These results suggest overlapping polyQ-mediated pathogenic mechanisms in HD and HDL2 PMID:21555070

  3. Adult-onset opsoclonus-myoclonus-ataxia syndrome as a manifestation of brazilian lyme disease-like syndrome: a case report and review of literature

    PubMed Central

    Spera, Raphael Ribeiro; de Campos, Fernando Peixoto Ferraz; Freitas, Christian Henrique de Andrade; Garcia, Márcio Ricardo Taveira; Lopes, Leonardo da Costa; Prokopowitsch, Aleksander Snioka

    2014-01-01

    Described in 1962, the opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare, neurologically debilitating disorder with distinct characteristics that may begin in childhood or adult life. Although many cases remain without etiological diagnosis, others are related to neoplasms and infectious diseases. We report a 41-year-old previously healthy male with an 8-day history of headache, vertigo, nausea, vomiting, and nystagmus. After a normal brain computed tomography and lymphocytic pleocytosis in cerebral spinal fluid (CSF), intravenous acyclovir therapy was initiated in the emergency room. On the third day of hospitalization, the diagnosis of OMAS was made based on the presence of chaotic and irregular eye movements, dysarthric speech, gait instability, generalized tremor, and myoclonic jerks. In the face of his neurological worsening, ampicillin followed by nonspecific immunotherapy (methylprednisolone and intravenous immunoglobulin) was prescribed, with mild clinical improvement. After a thorough laboratory workup, the definite diagnosis of neuroborreliosis was established and ceftriaxone (4 g/daily/3 wks) and doxycycline (200 mg/day/2 mo) was administered. Toward the end of the ceftriaxone regimen, the neurologic signs substantially improved. We believe this to be the first case description of OMAS as clinical presentation of Brazilian Lyme disease-like syndrome (Baggio-Yoshinari syndrome). PMID:28652990

  4. Presence of a carboxy-terminal pseudorepeat and disease-like pseudohyperphosphorylation critically influence tau’s interaction with microtubules in axon-like processes

    PubMed Central

    Niewidok, Benedikt; Igaev, Maxim; Sündermann, Frederik; Janning, Dennis; Bakota, Lidia; Brandt, Roland

    2016-01-01

    A current challenge of cell biology is to investigate molecular interactions in subcellular compartments of living cells to overcome the artificial character of in vitro studies. To dissect the interaction of the neuronal microtubule (MT)-associated protein tau with MTs in axon-like processes, we used a refined fluorescence decay after photoactivation approach and single-molecule tracking. We found that isoform variation had only a minor influence on the tau–MT interaction, whereas the presence of a C-terminal pseudorepeat region (PRR) greatly increased MT binding by a greater-than-sixfold reduction of the dissociation rate. Bioinformatic analysis revealed that the PRR contained a highly conserved motif of 18 amino acids. Disease-associated tau mutations in the PRR (K369I, G389R) did not influence apparent MT binding but increased its dynamicity. Simulation of disease-like tau hyperphosphorylation dramatically diminished the tau–MT interaction by a greater-than-fivefold decrease of the association rate with no major change in the dissociation rate. Apparent binding of tau to MTs was similar in axons and dendrites but more sensitive to increased phosphorylation in axons. Our data indicate that under the conditions of high MT density that prevail in the axon, tau’s MT binding and localization are crucially affected by the presence of the PRR and tau hyperphosphorylation. PMID:27582388

  5. Management of sickle cell disease in patients undergoing cardiac surgery.

    PubMed

    Crawford, Todd C; Carter, Michael V; Patel, Rina K; Suarez-Pierre, Alejandro; Lin, Sophie Z; Magruder, Jonathan Trent; Grimm, Joshua C; Cameron, Duke E; Baumgartner, William A; Mandal, Kaushik

    2017-02-01

    Sickle cell disease is a life-limiting inherited hemoglobinopathy that poses inherent risk for surgical complications following cardiac operations. In this review, we discuss preoperative considerations, intraoperative decision-making, and postoperative strategies to optimize the care of a patient with sickle cell disease undergoing cardiac surgery. © 2017 Wiley Periodicals, Inc.

  6. Unemployment risk among individuals undergoing medical treatment for chronic diseases.

    PubMed

    Nakaya, N; Nakamura, T; Tsuchiya, N; Tsuji, I; Hozawa, A; Tomita, H

    2016-03-01

    Chronic diseases increase the risk of unemployment even in non-disaster settings; therefore, in post-disaster settings, special attention needs to be paid to the employment status of those suffering from chronic diseases. To examine the association between chronic disease and the risk of unemployment in a disaster area. This cross-sectional study was conducted in Shichigahama Town, Miyagi, north-eastern Japan, where had been severely inundated by the 2011 tsunami. Logistic regression analyses were used to evaluate the association between undergoing medical treatment for a combination of chronic diseases (stroke, cancer, myocardial infarction and angina) and unemployment risk. Confounders such as psychological distress and levels of daily life activity were considered. Among the 2588 individuals studied, there was a statistically significant association between undergoing medical treatment for chronic disease and the risk of unemployment [odds ratio (OR) = 1.7, 95% confidence interval (CI) 1.02-2.7, P < 0.05]. In participants with a lower degree of psychological distress and better levels of daily life activity (n = 1967), no significant associations were observed (OR = 1.1, 95% CI 0.6-2.1). Conversely, in 536 participants with a higher degree of psychological distress and/or poorer levels of daily life activity, statistically significant associations were found (OR = 2.6, 95% CI 1.01-6.6, P < 0.05). The association between undergoing medical treatment for chronic disease and unemployment risk was observed only in participants with a higher degree of psychological distress and/or poorer levels of daily life activity. © The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Differential effects of voluntary treadmill exercise and caloric restriction on tau pathogenesis in a mouse model of Alzheimer's disease-like tau pathology fed with Western diet.

    PubMed

    Gratuze, Maud; Julien, Jacinthe; Morin, Françoise; Marette, André; Planel, Emmanuel

    2017-10-03

    Tau is a microtubule-associated protein that becomes pathological when it undergoes hyperphosphorylation and aggregation as seen in Alzheimer's disease (AD). AD is mostly sporadic, with environmental, biological and/or genetic risks factors, interacting together to promote the disease. In the past decade, reports have suggested that obesity in midlife could be one of these risk factors. On the other hand, caloric restriction and physical exercise have been reported to reduce the incidence and outcome of obesity as well as AD. We evaluated the impact of voluntary physical exercise and caloric restriction on tau pathology during 2months in hTau mice under high caloric diet in order to evaluate if these strategies could prevent AD-like pathology in obese conditions. We found no effects of obesity induced by Western diet on both Tau phosphorylation and aggregation compared to controls. However, exercise reduced tau phosphorylation while caloric restriction exacerbated its aggregation in the brains of obese hTau mice. We then examined the mechanisms underlying changes in tau phosphorylation and aggregation by exploring major tau kinases and phosphatases and key proteins involved in autophagy. However, there were no significant effects of voluntary exercise and caloric restriction on these proteins in hTau mice that could explain our results. In this study, we report differential effects of voluntary treadmill exercise and caloric restriction on tau pathogenesis in our obese mice, namely beneficial effect of exercise on tau phosphorylation and deleterious effect of caloric restriction on tau aggregation. Our results suggest that lifestyle strategies used to reduce metabolic disorders and AD must be selected and studied carefully to avoid exacerbation of pathologies. Copyright © 2017. Published by Elsevier Inc.

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

    SciTech Connect

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

    2015-03-01

    Clostridium histolyticumcollagenases ColG and ColH are segmental enzymes that are thought to be activated by Ca2+-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 Ca2+-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 Ca2+-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 Ca2+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 Ca2+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

  9. Tau pathology in aged cynomolgus monkeys is progressive supranuclear palsy/corticobasal degeneration- but not Alzheimer disease-like -Ultrastructural mapping of tau by EDX.

    PubMed

    Uchihara, Toshiki; Endo, Kentaro; Kondo, Hiromi; Okabayashi, Sachi; Shimozawa, Nobuhiro; Yasutomi, Yasuhiro; Adachi, Eijiro; Kimura, Nobuyuki

    2016-11-14

    Concomitant deposition of amyloid -beta protein (Aβ) and neuronal tau as neurofibrillary tangles in the human brain is a hallmark of Alzheimer disease (AD). Because these deposits increase during normal aging, it has been proposed that aging brains may also undergo AD-like changes. To investigate the neuropathological changes that occur in the aging primate brain, we examined 21 brains of cynomolgus monkeys (7-36 years old) for Aβ- and tau-positive lesions. We found, 1) extensive deposition of Aβ in brains of cynomolgus monkeys over 25 years of age, 2) selective deposition of 4-repeat tau as pretangles in neurons, and as coiled body-like structures in oligodendroglia-like cells and astrocytes, 3) preferential distribution of tau in the basal ganglia and neocortex rather than the hippocampus, and 4) age-associated increases in 30-34 kDa AT8- and RD4-positive tau fragments in sarkosyl-insoluble fractions. We further labeled tau-positive structures using diaminobezidine enhanced with nickel, and visualized nickel-labeled structures by energy-dispersive X-ray (EDX) analysis of ultrathin sections. This allowed us to distinguish between nickel-labeled tau and background electron-dense structures, and we found that tau localized to 20-25 nm straight filaments in oligodendroglia-like cells and neurons. Our results indicate that the cytopathology and distribution of tau deposits in aged cynomolgus brains resemble those of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) rather than AD. Thus, even in the presence of Aβ, age-associated deposition of tau in non-human primates likely does not occur through AD-associated mechanisms.

  10. Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis.

    PubMed

    Chertow, Glenn M; Block, Geoffrey A; Correa-Rotter, Ricardo; Drüeke, Tilman B; Floege, Jürgen; Goodman, William G; Herzog, Charles A; Kubo, Yumi; London, Gerard M; Mahaffey, Kenneth W; Mix, T Christian H; Moe, Sharon M; Trotman, Marie-Louise; Wheeler, David C; Parfrey, Patrick S

    2012-12-27

    Disorders of mineral metabolism, including secondary hyperparathyroidism, are thought to contribute to extraskeletal (including vascular) calcification among patients with chronic kidney disease. It has been hypothesized that treatment with the calcimimetic agent cinacalcet might reduce the risk of death or nonfatal cardiovascular events in such patients. In this clinical trial, we randomly assigned 3883 patients with moderate-to-severe secondary hyperparathyroidism (median level of intact parathyroid hormone, 693 pg per milliliter [10th to 90th percentile, 363 to 1694]) who were undergoing hemodialysis to receive either cinacalcet or placebo. All patients were eligible to receive conventional therapy, including phosphate binders, vitamin D sterols, or both. The patients were followed for up to 64 months. The primary composite end point was the time until death, myocardial infarction, hospitalization for unstable angina, heart failure, or a peripheral vascular event. The primary analysis was performed on the basis of the intention-to-treat principle. The median duration of study-drug exposure was 21.2 months in the cinacalcet group, versus 17.5 months in the placebo group. The primary composite end point was reached in 938 of 1948 patients (48.2%) in the cinacalcet group and 952 of 1935 patients (49.2%) in the placebo group (relative hazard in the cinacalcet group vs. the placebo group, 0.93; 95% confidence interval, 0.85 to 1.02; P=0.11). Hypocalcemia and gastrointestinal adverse events were significantly more frequent in patients receiving cinacalcet. In an unadjusted intention-to-treat analysis, cinacalcet did not significantly reduce the risk of death or major cardiovascular events in patients with moderate-to-severe secondary hyperparathyroidism who were undergoing dialysis. (Funded by Amgen; EVOLVE ClinicalTrials.gov number, NCT00345839.).

  11. Thymoma-associated multi-organ autoimmunity: A case of graft-versus-host disease-like erythroderma complicated by Good syndrome successfully treated by thymectomy.

    PubMed

    Fukushima, Ayano; Ichimura, Yoshiko; Obata, Shoko; Kinoshita-Ise, Misaki; Fujio, Yumi; Takeno, Mitsuhiro; Konohana, Izumi

    2017-03-03

    Thymoma-associated multi-organ autoimmunity disease (TAMA) is a rare paraneoplastic disorder, clinicopathologically similar to graft-versus-host disease (GVHD). Many reported cases follow a difficult course; half of them die from serious infectious diseases subsequent to immunosuppression induced by chemotherapy for unresectable thymoma, or intensive therapies including systemic steroids for complicating autoimmune diseases and GVHD-like symptoms. We report a patient whose skin symptoms were improved subsequently to total thymectomy. The patient also presented with hypogammaglobulinemia, which led to the diagnosis of complicated Good syndrome. Taking account of her immunodeficient condition, antibiotics and i.v. immunoglobulin were administrated promptly on onset of bacterial pneumonia, which was successfully treated. According to a review of the published work, treatments with systemic steroids for skin symptoms have limited effects and may contribute to serious infection. Our case indicates that successful treatment of thymoma itself may lead to the amelioration of the disease. The management priority should be given to the treatment of thymoma and the control of subsequent immune abnormality other than GVHD-like erythroderma.

  12. Alzheimer's disease-like neuropathology of gene-targeted APP-SLxPS1mut mice expressing the amyloid precursor protein at endogenous levels.

    PubMed

    Köhler, Christoph; Ebert, Ulrich; Baumann, Karlheinz; Schröder, Hannsjörg

    2005-11-01

    Most transgenic mice used for preclinical evaluation of potential disease-modifying treatments of Alzheimer's disease develop major histopathological features of this disease by several-fold overexpression of the human amyloid precursor protein. We studied the phenotype of three different strains of gene-targeted mice which express the amyloid precursor protein at endogenous levels. Only further crossing with transgenic mice overexpressing mutant human presenilin1 led to the deposition of extracellular amyloid, accompanied by the deposition of apolipoprotein E, an astrocyte and microglia reaction, and the occurrence of dilated cholinergic terminals in the cortex. Features of neurodegeneration, however, were absent. The pattern of plaque development and deposition in these mice was similar to that of amyloid precursor protein overproducing strains if crossed to presenilin1-transgenics. However, plaque development started much later and developed slowly until the age of 18 months but then increased more rapidly.

  13. 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

  14. Rapidly Progressive Renal Dysfunction in Two Elderly Patients with Renal Enlargement and Medullary Cystic Kidney Disease-like Acute Tubulointerstitial Injury

    PubMed Central

    Kawamoto, Shinya; Koda, Ryo; Yoshino, Atsunori; Takeda, Tetsuro; Ueda, Yoshihiko

    2016-01-01

    Medullary cystic kidney disease (MCKD) is a hereditary disease associated with bilateral medullary polycysts and interstitial fibrosis. MCKD is typically associated with slowly progressive renal dysfunction. We herein report two rare elderly cases with enlarged kidneys and rapidly progressive renal dysfunction without myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA), PR3-ANCA, or anti-glomerular basement membrane (GBM) antibodies. Renal biopsies revealed extensive tubular dilatation and atrophy with interstitial fibrosis consistent with MCKD. Both patients began hemodialysis therapy a few months later. Our cases suggest a MCKD subgroup among elderly patients with an undefined genetic background, rapidly progressive renal dysfunction, and enlarged kidneys. PMID:27746439

  15. Conditional deletion of Ndufs4 in dopaminergic neurons promotes Parkinson’s disease-like non-motor symptoms without loss of dopamine neurons

    PubMed Central

    Choi, Won-Seok; Kim, Hyung-Wook; Tronche, François; Palmiter, Richard D.; Storm, Daniel R.; Xia, Zhengui

    2017-01-01

    Reduction of mitochondrial complex I activity is one of the major hypotheses for dopaminergic neuron death in Parkinson’s disease. However, reduction of complex I activity in all cells or selectively in dopaminergic neurons via conditional deletion of the Ndufs4 gene, a subunit of the mitochondrial complex I, does not cause dopaminergic neuron death or motor impairment. Here, we investigated the effect of reduced complex I activity on non-motor symptoms associated with Parkinson’s disease using conditional knockout (cKO) mice in which Ndufs4 was selectively deleted in dopaminergic neurons (Ndufs4 cKO). This conditional deletion of Ndufs4, which reduces complex I activity in dopamine neurons, did not cause a significant loss of dopaminergic neurons in substantia nigra pars compacta (SNpc), and there was no loss of dopaminergic neurites in striatum or amygdala. However, Ndufs4 cKO mice had a reduced amount of dopamine in the brain compared to control mice. Furthermore, even though motor behavior were not affected, Ndufs4 cKO mice showed non-motor symptoms experienced by many Parkinson’s disease patients including impaired cognitive function and increased anxiety-like behavior. These data suggest that mitochondrial complex I dysfunction in dopaminergic neurons promotes non-motor symptoms of Parkinson’s disease and reduces dopamine content in the absence of dopamine neuron loss. PMID:28327638

  16. Incidental adenocarcinoma in patients undergoing surgery for stricturing Crohn's disease

    PubMed Central

    Kristo, Ivan; Riss, Stefan; Argeny, Stanislaus; Maschke, Svenja; Chitsabesan, Praminthra; Stift, Anton

    2017-01-01

    AIM To evaluate frequency and clinical course of incidental adenocarcinoma in patients with stricturing Crohn's disease (CD). METHODS In this study, consecutive patients, who were operated on for stricturing CD between 1997-2012, were included at an academic tertiary referral center. Demographic data and clinical course were obtained by an institutional database and individual chart review. Besides baseline characteristics, intraoperative findings and CD related history were also recorded. Colorectal cancer was classified and staged according to the Union for International Cancer Control (UICC). RESULTS During the study period 484 patients underwent resections due to stricturing CD. Incidental adenocarcinoma was histologically confirmed in 6 (1.2%) patients (4 males, 2 females). Patients diagnosed with colorectal cancer had a median age of 43 (27-66) years and a median history of CD of 16 (7-36) years. Malignant lesions were found in the rectum (n = 4, 66.7%), descending colon (n = 1, 16.7%) and ileocolon (n = 1, 16.7%). According to the UICC classification two patients were stages as I (33.3%), whereas the other patients were classified as stage IIA (16.7%), stage IIIB (16.7%), stage IIIC (16.7%) and stage IV (16.7%), respectively. After a median follow-up of 2 (0.03-8) years only 1 patient is still alive. CONCLUSION The frequency of incidental colorectal cancer in patients, who undergo surgery for stenotic CD, is low but associated with poor prognosis. However, surgeons need to be aware about the possibility of malignancy in stricturing CD, especially if localized in the rectum. PMID:28210083

  17. A novel model of colitis-associated cancer in SAMP1/YitFc mice with Crohn’s disease-like ileitis

    PubMed Central

    Menghini, Paola; Di Martino, Luca; Lopetuso, Loris R.; Corridoni, Daniele; Webster, Joshua C.; Xin, Wei; Arseneau, Kristen O.; Lam, Minh; Pizarro, Theresa T.

    2017-01-01

    Patients with inflammatory bowel disease (IBD) are at increased risk for developing colorectal cancer. Evidence suggests that colonic dysplasia and colitis-associated cancer (CAC) are often linked to repeated cycles of epithelial cell injury and repair in the context of chronic production of inflammatory cytokines. Several mouse models of CAC have been proposed, including chemical induction through exposure to dextran sulfate sodium (DSS) with the genotoxic agents azoxymethane (AOM), 1,2-dymethylhydrazine (DHM) or targeted genetic mutations. However, such models are usually performed on healthy animals that usually lack the underlying genetic predisposition, immunological dysfunction and dysbiosis characteristic of IBD. We have previously shown that inbred SAMP1/YitFc (SAMP) mice develop a progressive Crohn’s disease (CD)-like ileitis in the absence of spontaneous colitis. We hypothesize that SAMP mice may be more susceptible to colonic tumorigenesis due to their predisposition to IBD. To test this hypothesis, we administered AOM/DSS to IBD-prone SAMP and their non-inflamed parental control strain, AKR mice. Our results showed that AOM/DSS treatment enhanced the susceptibility of colitis in SAMP compared to AKR mice, as assessed by endoscopic and histologic inflammatory scores, daily weight loss and disease activity index (DAI), during and after DSS administration. SAMP mice also showed increased colonic tumorigenesis, resulting in the occurrence of intramucosal carcinoma and a higher incidence of high-grade dysplasia and tumor burden. These phenomena occurred even in the absence of AOM and only upon repeated cycles of DSS. Taken together, our data demonstrate a heightened susceptibility to colonic inflammation and tumorigenesis in AOM/DSS-treated SAMP mice with CD-like ileitis. This novel model represents a useful tool to investigate relevant mechanisms of CAC, as well as for pre-clinical testing of potential IBD and colon cancer therapeutics. PMID:28301579

  18. 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.

  19. Long-term treadmill exercise inhibits the progression of Alzheimer's disease-like neuropathology in the hippocampus of APP/PS1 transgenic mice.

    PubMed

    Liu, Hui-li; Zhao, Gang; Zhang, He; Shi, Li-de

    2013-11-01

    Previously our study has demonstrated that long-term treadmill exercise improved cognitive deficit in APP/PS1 transgenic mice of Alzheimer's disease (AD) paralleled by enhanced long-term potentiation (LTP). The present study was undertaken to further investigate whether the treadmill running could inhibit the progression of Alzheimer's disease (AD)-like neuropathology in hippocampus of the APP/PS1 mouse models of AD, and to define a potential molecular mechanism underlying the exercise-induced reduction in AD-like neuropathology. Five months of treadmill exercise resulted in a robust reduction in β-amyloid (Aβ) deposition and tau phosphorylation in the hippocampus of APP/PS1 mice. This was accompanied by a significant decrease in APP phosphorylation and PS1 expression. We also observed GSK3, rather than CDK5, was inhibited by treadmill exercise. These results indicate that treadmill exercise is sufficient to inhibit the progression of AD-like neuropathology in the hippocampus of APP/PS1 transgenic mouse model, and may mediate APP processing in favor of reduced Aβ deposition. In addition, we demonstrate that treadmill exercise attenuates AD-like neuropathology in AD transgenic mice via a GSK3 dependent signaling pathway.

  20. 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.

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

    PubMed

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

    2016-01-13

    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. 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 characterize the neurodegeneration

  2. 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

  3. High-fat, high-sugar, and high-cholesterol consumption does not impact tau pathogenesis in a mouse model of Alzheimer's disease-like tau pathology.

    PubMed

    Gratuze, Maud; Julien, Jacinthe; Morin, Françoise; Calon, Frédéric; Hébert, Sébastien S; Marette, André; Planel, Emmanuel

    2016-11-01

    Aggregates of hyperphosphorylated tau protein are a pathological hallmark of Alzheimer's disease (AD). The origin of AD is multifactorial, and many metabolic disorders originating from overconsumption of fat, cholesterol, and sugar are associated with higher risk of AD later in life. However, the effects of fat, cholesterol, and sugar overconsumption on tau pathology in AD remain controversial. Using the hTau mice, a model of AD-like tau pathology, we assessed the effects of high-fat, high-cholesterol, and/or high-sugar diets on tau pathogenesis. Surprisingly, we found no effects of these compounds, even combined, on tau phosphorylation, O-GlcNAcylation, splicing, cleavage, and aggregation, suggesting that their overconsumption does not seem to worsen tau pathology in these mice.

  4. Creutzfeldt-Jakob disease-like periodic sharp wave complexes in voltage-gated potassium channel-complex antibodies encephalitis : A Case Report

    PubMed Central

    Savard, Martin; Irani, Sarosh R.; Guillemette, Annie; Gosselin-Lefebvre, Stéphanie; Geschwind, Michael; Jansen, Gerard H.; Gould, Peter V.; Laforce, Robert

    2015-01-01

    Introduction Voltage-gated potassium channel-complex antibodies (VGKC-cAbs) encephalitis, a treatable autoantibody encephalopathy, has been previously reported to clinically mimic sporadic Creutzfeldt-Jacob disease (sCJD). Among available clinical clues to distinguish them, periodic sharp wave complexes (PSWC), a typical finding in sCJD, have never been reported in association with VGKC-cAbs encephalitis. Case presentation A 76 years old man was transferred to a tertiary neurology center with a clinical history of six-month weight loss, cognitive disturbance and non specific generalized weakness. He had two seizures the month before transfer and then evolved to severe encephalopathy, requiring mechanical ventilation. PSWC every 1–2 seconds over slowed background were found on EEG, and MRI showed cerebellar and bifrontal cortical T2/FLAIR/DWI hypersignal without restricted diffusion on ADC mapping. Pancorporal PET-scan was negative. An immunotherapy trial did not improve the patient condition. Therefore, he died after life support withdrawal. Brain autopsy revealed mononuclear neocortex infiltrate without significant spongiosis, and the anti-VGKC test showed a seropositivity of 336 pmol/L (normal: 0–31), three month after the patient deceased. Conclusion This is the first reported case of VGKC-cAbs encephalitis associated with PSWC on EEG, which further confuse the differential diagnosis with sCJD. However, the cortical DWI hypersignal without restriction seem to remain a way to discriminate these two entities appropriately, when present. These clues are of paramount importance since VGKC-cAbs encephalitis is a treatable disease. PMID:26375660

  5. 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.

  6. Minocycline corrects early, pre-plaque neuroinflammation and inhibits BACE-1 in a transgenic model of Alzheimer's disease-like amyloid pathology.

    PubMed

    Ferretti, Maria Teresa; Allard, Simon; Partridge, Vanessa; Ducatenzeiler, Adriana; Cuello, A Claudio

    2012-04-02

    A growing body of evidence indicates that inflammation is one of the earliest neuropathological events in Alzheimer's disease. Accordingly, we have recently shown the occurrence of an early, pro-inflammatory reaction in the hippocampus of young, three-month-old transgenic McGill-Thy1-APP mice in the absence of amyloid plaques but associated with intracellular accumulation of amyloid beta petide oligomers. The role of such a pro-inflammatory process in the progression of the pathology remained to be elucidated. To clarify this we administered minocycline, a tetracyclic derivative with anti-inflammatory and neuroprotective properties, to young, pre-plaque McGill-Thy1-APP mice for one month. The treatment ended at the age of three months, when the mice were still devoid of plaques. Minocycline treatment corrected the up-regulation of inducible nitric oxide synthase and cyclooxygenase-2 observed in young transgenic placebo mice. Furthermore, the down-regulation of inflammatory markers correlated with a reduction in amyloid precursor protein levels and amyloid precursor protein-related products. Beta-site amyloid precursor protein cleaving enzyme 1 activity and levels were found to be up-regulated in transgenic placebo mice, while minocycline treatment restored these levels to normality. The anti-inflammatory and beta-secretase 1 effects could be partly explained by the inhibition of the nuclear factor kappa B pathway. Our study suggests that the pharmacological modulation of neuroinflammation might represent a promising approach for preventing or delaying the development of Alzheimer's disease neuropathology at its initial, pre-clinical stages. The results open new vistas to the interplay between inflammation and amyloid pathology.

  7. 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

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

    PubMed

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

    2015-01-01

    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.

  9. Paraquat exposure-induced Parkinson's disease-like symptoms and oxidative stress in Drosophila melanogaster: Neuroprotective effect of Bougainvillea glabra Choisy.

    PubMed

    Soares, Jefferson J; Rodrigues, Daniela T; Gonçalves, Mayara B; Lemos, Maurício C; Gallarreta, Mariana S; Bianchini, Matheus C; Gayer, Mateus C; Puntel, Robson L; Roehrs, Rafael; Denardin, Elton L G

    2017-08-24

    Extracts from the leaves of Bougainvillea glabra Choisy are used in traditional medicines, but their actions on the central nervous system have not been studied. In the present study, we investigated the potential neuroprotective effects of Bougainvillea glabra Choisy leaf extract (BG extract) against paraquat (PQ)-induced neurotoxicity. Male adult wild-type flies (1- 4days old) were exposed to PQ (3.5mM) and/or BG extract (120μg/mL) through food for 4days. PQ-fed flies had decreased locomotor capacity in negative geotaxis and crossing number assays and had a higher incidence of mortality than the control group. PQ neurotoxicity was also associated with a marked decrease in dopamine levels and increase in acetylcholinesterase (AChE) activity, reactive oxygen species (ROS) production and lipid peroxidation. Co-exposure to BG extract prevented mortality, and dopamine depletion, improved locomotor performance and decreased AChE activity, ROS production and lipid peroxidation. GC-MS and HPLC analyses of BG extract revealed the presence of many antioxidant compounds such as phytol, α,γ-tocopherol, squalene, stigmasterol, geranylgeraniol, quercetin, and caffeic, vanillic, coumaric, ferulic acids. Our results showed neuroprotective effects of BG extract, reflecting the presence of antioxidant compounds. Thus, we suggested that B. glabra leaves could be considered an effective agent in the prevention of neurological disorders, where dopamine depletion and/or oxidative stress are involved, as in Parkinson's disease (PD). Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  10. Chronic Sleep Deprivation Exacerbates Learning-Memory Disability and Alzheimer's Disease-Like Pathologies in AβPP(swe)/PS1(ΔE9) Mice.

    PubMed

    Qiu, Hongyan; Zhong, Rujia; Liu, Hui; Zhang, Feng; Li, Song; Le, Weidong

    2016-01-01

    Recently, there is an increasing concern over the association between sleep disorders and Alzheimer's disease (AD). Clinical observations have reported that chronic sleep deprivation (SD) may serve as a risk factor for AD. However, the pathological evidence for this assumption is still lacking. In the present study, we examined the potential impacts of chronic SD on learning-memory and AD-related pathologies in AβPP(swe)/PS1(ΔE9) transgenic (TG) mice and their wild-type (WT) littermates. Results indicated that mice (both TG and WT) exposed to 2-month SD showed an altered amyloid-β protein precursor processing, an elevated level of phosphorylated tau protein, and impaired cognitive performance as compared to non-sleep deprivation (NSD) controls. Moreover, the SD-treated TG mice exhibited more amyloid-β(1-42) production and developed more senile plaques in the cortex and hippocampus than NSD-treated TG mice. In addition, SD caused a striking neuronal mitochondrial damage, caspase cascade activation, and neuronal apoptosis in the hippocampus of both TG and WT mice. More importantly, all these behavioral, neuropathological, and biochemical changes induced by chronic SD were long lasting and were irreversible during a 3-month normal housing condition. Collectively, these results indicate that chronic SD impairs learning and memory, exacerbates AD pathologies, and aggravates the mitochondria-mediated neuronal apoptosis in a long-lasting manner. Our findings provide important experimental evidence to prove that chronic SD is a risk factor for AD.

  11. Caffeine protects against oxidative stress and Alzheimer’s disease-like pathology in rabbit hippocampus induced by cholesterol-enriched diet

    PubMed Central

    Prasanthi, Jaya R.P.; Dasari, Bhanu; Marwarha, Gurdeep; Larson, Tyler; Chen, Xuesong; Geiger, Jonathan D.; Ghribi, Othman

    2010-01-01

    Cholesterol has been linked to the pathogenesis of sporadic Alzheimer’s disease (AD) as a risk factor increasing β-amyloid (Aβ) and oxidative stress levels. Caffeine has anti-oxidant properties and has been demonstrated to reduce Aβ levels in transgenic mouse models of familial AD. However, the effects of caffeine on cholesterol-induced sporadic AD pathology have not been determined. In the present study, we determined the effects of caffeine on Aβ levels, tau phosphorylation, oxidative stress generation, and caffeine-target receptors in rabbits fed a 2% cholesterol-enriched diet, a model system for sporadic AD. Our results showed that the cholesterol-enriched diet increased levels of Aβ, tau phosphorylation as well as oxidative stress measured as increased levels of reactive oxygen species, isoprostanes, glutathione depletion, and increased levels of endoplasmic reticulum (ER) stress marker proteins. Additionally, the cholesterol-enriched diet reduced levels of adenosine A1 (A1R) but not ryanodine (RyR) or adenosine A2A (A2AR) receptors. Caffeine, administered at 0.5 mg and 30 mg/day in the drinking water, reduced cholesterol-induced increase in Aβ, phosphorylated tau and oxidative stress levels, and reversed cholesterol-induced decrease in A1R levels. Our results suggest that even very low doses of caffeine might protect against sporadic AD-like pathology. PMID:20638472

  12. Alzheimer's disease-like pathology in senescence-accelerated OXYS rats can be partially retarded with mitochondria-targeted antioxidant SkQ1.

    PubMed

    Stefanova, Natalia A; Muraleva, Natalia A; Skulachev, Vladimir P; Kolosova, Nataliya G

    2014-01-01

    We previously showed that mitochondria-targeted antioxidant SkQ1 (plastoquinonyl-decyltriphenylphosphonium) at nanomolar concentrations is capable of preventing and slowing down some cerebral dysfunctions in accelerated-senescence OXYS rats. Here we demonstrate that OXYS rats develop behavior, learning, and memory deficits against a background of neurodegeneration signs detected by magnetic resonance tomography and amyloid-β (Aβ) pathology similar to those seen in Alzheimer's disease (AD). Long-term treatment with SkQ1 (250 nmol/kg body weight daily from the age of 1.5 to 23 months) reduced the age-related alterations in behavior and spatial memory deficit in Morris water maze in OXYS and Wistar rats. Furthermore, this is the first report that SkQ1 treatment slows down pathological accumulation of AβPP, Aβ, and hyperphosphorylation of tau-protein in OXYS rats, as well as age-dependent changes in healthy Wistar rats. Our results support the possibility of using the OXYS strain as a rat model of AD-like pathology. It seems probable that the mitochondria-targeted antioxidant SkQ1 can be a good prophylactic strategy to maintain brain health and to treat AD.

  13. Total body 100-mGy X-irradiation does not induce Alzheimer's disease-like pathogenesis or memory impairment in mice

    PubMed Central

    Wang, Bing; Tanaka, Kaoru; Ji, Bin; Ono, Maiko; Fang, Yaqun; Ninomiya, Yasuharu; Maruyama, Kouichi; Izumi-Nakajima, Nakako; Begum, Nasrin; Higuchi, Makoto; Fujimori, Akira; Uehara, Yoshihiko; Nakajima, Tetsuo; Suhara, Tetsuya; Ono, Tetsuya; Nenoi, Mitsuru

    2014-01-01

    The cause and progression of Alzheimer's disease (AD) are poorly understood. Possible cognitive and behavioral consequences induced by low-dose radiation are important because humans are exposed to ionizing radiation from various sources. Early transcriptional response in murine brain to low-dose X-rays (100 mGy) has been reported, suggesting alterations of molecular networks and pathways associated with cognitive functions, advanced aging and AD. To investigate acute and late transcriptional, pathological and cognitive consequences of low-dose radiation, we applied an acute dose of 100-mGy total body irradiation (TBI) with X-rays to C57BL/6J Jms mice. We collected hippocampi and analyzed expression of 84 AD-related genes. Mouse learning ability and memory were assessed with the Morris water maze test. We performed in vivo PET scans with 11C-PIB, a radiolabeled ligand for amyloid imaging, to detect fibrillary amyloid beta peptide (Aβ) accumulation, and examined characteristic AD pathologies with immunohistochemical staining of amyloid precursor protein (APP), Aβ, tau and phosphorylated tau (p-tau). mRNA studies showed significant downregulation of only two of 84 AD-related genes, Apbb1 and Lrp1, at 4 h after irradiation, and of only one gene, Il1α, at 1 year after irradiation. Spatial learning ability and memory were not significantly affected at 1 or 2 years after irradiation. No induction of amyloid fibrillogenesis or changes in APP, Aβ, tau, or p-tau expression was detected at 4 months or 2 years after irradiation. TBI induced early or late transcriptional alteration in only a few AD-related genes but did not significantly affect spatial learning, memory or AD-like pathological change in mice. PMID:23908553

  14. Role of Endoplasmic Reticulum Stress in Learning and Memory Impairment and Alzheimer's Disease-Like Neuropathology in the PS19 and APPSwe Mouse Models of Tauopathy and Amyloidosis

    PubMed Central

    Briggs, Denise Isabelle; Defensor, Erwin; Memar Ardestani, Pooneh; Yi, Bitna; Halpain, Michelle; Seabrook, Guy

    2017-01-01

    Abstract Emerging evidence suggests that endoplasmic reticulum (ER) stress may be involved in the pathogenesis of Alzheimer’s disease (AD). Recently, pharmacological modulation of the eukaryotic translation initiation factor-2 (eIF2α) pathway was achieved using an integrated stress response inhibitor (ISRIB). While members of this signaling cascade have been suggested as potential therapeutic targets for neurodegeneration, the biological significance of this pathway has not been comprehensively assessed in animal models of AD. The present study investigated the ER stress pathway and its long-term modulation utilizing in vitro and in vivo experimental models of tauopathy (MAPT P301S)PS19 and amyloidosis (APPSwe). We report that thapsigargin induces activating transcription factor-4 (ATF4) in primary cortical neurons (PCNs) derived from rat and APPSwe nontransgenic (nTg) and transgenic (Tg) mice. ISRIB mitigated the induction of ATF4 in PCNs generated from wild-type (WT) but not APPSwe mice despite partially restoring thapsigargin-induced translational repression in nTg PCNs. In vivo, C57BL/6J and PS19 mice received prolonged, once-daily administration of ISRIB. While the compound was well tolerated by PS19 and C57BL/6J mice, APPSwe mice treated per this schedule displayed significant mortality. Thus, the dose was reduced and administered only on behavioral test days. ISRIB did not improve learning and memory function in APPSwe Tg mice. While ISRIB did not reduce tau-related neuropathology in PS19 Tg mice, no evidence of ER stress-related dysfunction was observed in either of these Tg models. Taken together, the significance of ER stress and the relevance of these models to the etiology of AD require further investigation. PMID:28721361

  15. Live with the Disease Like You Used to Before You Knew You Were Infected: A Qualitative Study Among 10-Year Survivors Living with HIV in Haiti.

    PubMed

    Pierre, Samuel; Riviera, Vanessa; Jean, Circee Phara; Louis, Marie Jude Jean; Reif, Lindsey K; Severe, Patrice; Rouzier, Vanessa; Johnson, Warren D; Pape, Jean W; Fitzgerald, Daniel W; McNairy, Margaret L; Boutin-Foster, Carla

    2017-03-01

    In 2003, the Haitian Study Group on Kaposi's Sarcoma and Opportunistic Infections (GHESKIO), a nonprofit organization, began administering antiretroviral therapy (ART) to its patients. This practice transformed HIV from a fatal disease to a more manageable chronic condition. However, relatively few studies focus on the experiences of survivors. This study provided a unique opportunity to interview patients who survived at least 10 years after being treated with ART at GHESKIO. The goal of the study was to elicit from patients their perspectives on what enabled them to survive with AIDS. Grounded Theory, a qualitative research method was used to guide data collection, coding, and analysis. Individual interviews were conducted, audio-taped, transcribed and analyzed in Creole, and translated into English. Data saturation was reached at 25 participants. Of which, 64% were women, the mean age was 49, range of 43-55 years, 24% were married, 44% had not completed elementary school, and 72% had no income, the remaining participants had incomes ranging from $1000 to $5000 annually. Qualitative analysis resulted in 681 codes, which were grouped into six categories: being spiritually grounded, having supportive interactions with providers, caring for children, setting personal goals, persevering and living life as usual, and maintaining strict medication adherence practices. The overarching theory was that having a reason to live despite one's circumstances and living life as usual enabled one to survive. Having a strong spiritual foundation coupled with supportive family and providers motivated participants to live and adhere to their ART. As the number of patients who are living longer with HIV in Haiti increases, results from this study will be important in helping tailor interventions that enhance their overall quality of life.

  16. Temporal changes of CD68 and α7 nicotinic acetylcholine receptor expression in microglia in Alzheimer's disease-like mouse models.

    PubMed

    Matsumura, Akihiro; Suzuki, Syuuichirou; Iwahara, Naotoshi; Hisahara, Shin; Kawamata, Jun; Suzuki, Hiromi; Yamauchi, Ayano; Takata, Kazuyuki; Kitamura, Yoshihisa; Shimohama, Shun

    2015-01-01

    We previously reported that activated microglia are involved in amyloid-β (Aβ) clearance and that stimulation of α7 nicotinic acetylcholine receptors (nAChR) in microglia enhances Aβ clearance. Nevertheless, how microglia and α7 nAChR in microglia are affected in Alzheimer's disease (AD) remains unknown. The present study aimed to collect fundamental data for considering whether microglia are potential targets for AD treatment and the appropriate timing of therapeutic intervention, by evaluating the temporal changes of Aβ, microglia, neurons, presynapses, and α7 nAChR by immunohistochemical studies in mouse models of AD. In an Aβ-injected AD mouse model, we observed early accumulation of CD68-positive microglia at Aβ deposition sites and gradual reduction of Aβ. Microglia were closely associated with Aβ deposits, and were confirmed to participate in clearing Aβ. In a transgenic mouse model of AD, we observed an increase in Aβ deposition from 6 months of age, followed by a gradual increase in microglial accumulation at Aβ deposit sites. Activated microglia in APdE9 mice showed two-step transition: a CD68-negative activated form at 6-9 months and a CD68-positive form from 12 months of age. In addition, α7 nAChR in microglia increased markedly at 6 months of age when activated microglia appeared for the first time, and decreased gradually coinciding with the increase of Aβ deposition. These findings suggest that early microglial activation is associated with α7 nAChR upregulation in microglia in APdE9 mice. These novel findings are important for the development of new therapeutic strategy for AD.

  17. Long-term prevention of Alzheimer’s disease-like behavioral deficits in PDAPP mice carrying a mutation in Asp664

    PubMed Central

    Galvan, Veronica; Zhang, Junli; Gorostiza, Olivia F.; Banwait, Surita; Huang, Wei; Ataie, Marina; Tang, Huidong; Bredesen, Dale E.

    2009-01-01

    The deficits of Alzheimer’s disease (AD) are believed to result, at least in part, from neurotoxicity of β-amyloid (Aβ), a set of 38–43 amino acid fragments derived from the β-amyloid precursor protein (APP). In addition, APP generates the APP-C31 and Jcasp toxic fragments intracellularly by cleavage at Asp664. We reported that mutation of Asp664 to A in a FAD-human APP transgene prevented AD-like deficits but did not affect Aβ production or deposition in PDAPP mice, arguing that D664A plays a crucial role in the generation of AD-like deficits. Whether D664A simply delays or completely prevents AD-like deficits, however, remained undefined. To address this question, we performed behavioral studies longitudinally on a pretrained mouse cohort at 9 and 13 months of age. While behavioral deficits were present in PDAPP mice, performance of Tg PDAPP(D664A) mice was not significantly different from non-Tg littermates’ across all ages tested. Moreover, aberrant patterns in non-cognitive components of behavior in PDAPP mice were ameliorated in PDAPP(D664A) animals as well. A trend towards poorer retention at 9 mo and poorer learning at 13 mo that did not reach statistical significance was observed in PDAPP(D664A) mice. These results support and extend recent studies showing that cleavage of APP at Asp664 (or protein-protein interactions dependent on Asp664) is a crucial event in the generation of AD-like deficits in PDAPP mice. Our results thus further demonstrate that the D664A mutation either completely precludes, or markedly delays (beyond 13 mo) the appearance of AD-like deficits in this mouse model of AD. PMID:18485495

  18. Relative importance of redox buffers GSH and NAD(P)H in age-related neurodegeneration and Alzheimer disease-like mouse neurons

    PubMed Central

    Ghosh, Debolina; Levault, Kelsey R; Brewer, Gregory J

    2014-01-01

    Aging, a major risk factor in Alzheimer’s disease (AD), is associated with an oxidative redox shift, decreased redox buffer protection, and increased free radical reactive oxygen species (ROS) generation, probably linked to mitochondrial dysfunction. While NADH is the ultimate electron donor for many redox reactions, including oxidative phosphorylation, glutathione (GSH) is the major ROS detoxifying redox buffer in the cell. Here, we explored the relative importance of NADH and GSH to neurodegeneration in aging and AD neurons from nontransgenic and 3xTg-AD mice by inhibiting their synthesis to determine whether NADH can compensate for the GSH loss to maintain redox balance. Neurons stressed by either depleting NAD(P)H or GSH indicated that NADH redox control is upstream of GSH levels. Further, although depletion of NAD(P)H or GSH correlated linearly with neuron death, compared with GSH depletion, higher neurodegeneration was observed when NAD(P)H was extrapolated to zero, especially in old age, and in the 3xTg-AD neurons. We also observed an age-dependent loss of gene expression of key redox-dependent biosynthetic enzymes, NAMPT (nicotinamide phosphoribosyltransferase), and NNT (nicotinamide nucleotide transhydrogenase). Moreover, age-related correlations between brain NNT or NAMPT gene expression and NADPH levels suggest that these genes contribute to the age-related declines in NAD(P)H. Our data indicate that in aging and more so in AD-like neurons, NAD(P)H redox control is upstream of GSH and an oxidative redox shift that promotes neurodegeneration. Thus, NAD(P)H generation may be a more efficacious therapeutic target upstream of GSH and ROS. PMID:24655393

  19. Angiotensin-(1-7) administration attenuates Alzheimer's disease-like neuropathology in rats with streptozotocin-induced diabetes via Mas receptor activation.

    PubMed

    Chen, Jin-Liang; Zhang, Dong-Ling; Sun, Yue; Zhao, Yu-Xing; Zhao, Ke-Xiang; Pu, Die; Xiao, Qian

    2017-03-27

    Diabetes mellitus (DM) is associated with cognitive deficits and an increased risk of Alzheimer's disease (AD). Recently, a newly identified heptapeptide of the renin-angiotensin system (RAS), angiotensin-(1-7) [Ang-(1-7)], was found to protect against brain damage. This study investigated the effects of Ang-(1-7) on diabetes-induced cognitive deficits. Sprague-Dawley rats were randomly divided into four groups. Diabetes was induced via single i.p. streptozotocin (STZ) injections. Ten weeks after diabetes induction, rats in each group received an intracerebral-ventricular (ICV) infusion of either vehicle, Ang-(1-7) alone, or Ang-(1-7)+A779 daily for two weeks. At the end of the study, Morris water maze (MWM) tests were performed to test cognitive functions before the rats were euthanized. Ang-(1-7) treatment significantly reduced escape latencies in diabetic rats in acquisition trials and markedly enhanced platform area crossing frequency and time spent in the target quadrant in probe trials (3.0±0.39 vs. 1.0±0.33, 39.39±1.11% vs. 25.62±3.07%, respectively, P<0.01). Ang-(1-7) treatment ameliorated damage to the ultrastructure of hippocampal synapses, reduced the expression of hippocampal phospho-tau at Ser396 (P<0.01), Ser404 (P<0.01) and Ser202/Thr205 (P<0.05), and decreased amyloid-β oligomer and both soluble and insoluble β-amyloid peptide 1-42 (Aβ 1-42) and Aβ 1-40 levels (P<0.01). These protective effects were significantly reversed by the co-administration of A779. These findings show that Ang-(1-7) is a promising therapeutic target for diabetes-induced cognitive impairment. The neuroprotective effects of Ang-(1-7) were mainly through Mas receptor (MasR) activation.

  20. Total body 100-mGy X-irradiation does not induce Alzheimer's disease-like pathogenesis or memory impairment in mice.

    PubMed

    Wang, Bing; Tanaka, Kaoru; Ji, Bin; Ono, Maiko; Fang, Yaqun; Ninomiya, Yasuharu; Maruyama, Kouichi; Izumi-Nakajima, Nakako; Begum, Nasrin; Higuchi, Makoto; Fujimori, Akira; Uehara, Yoshihiko; Nakajima, Tetsuo; Suhara, Tetsuya; Ono, Tetsuya; Nenoi, Mitsuru

    2014-01-01

    The cause and progression of Alzheimer's disease (AD) are poorly understood. Possible cognitive and behavioral consequences induced by low-dose radiation are important because humans are exposed to ionizing radiation from various sources. Early transcriptional response in murine brain to low-dose X-rays (100 mGy) has been reported, suggesting alterations of molecular networks and pathways associated with cognitive functions, advanced aging and AD. To investigate acute and late transcriptional, pathological and cognitive consequences of low-dose radiation, we applied an acute dose of 100-mGy total body irradiation (TBI) with X-rays to C57BL/6J Jms mice. We collected hippocampi and analyzed expression of 84 AD-related genes. Mouse learning ability and memory were assessed with the Morris water maze test. We performed in vivo PET scans with (11)C-PIB, a radiolabeled ligand for amyloid imaging, to detect fibrillary amyloid beta peptide (Aβ) accumulation, and examined characteristic AD pathologies with immunohistochemical staining of amyloid precursor protein (APP), Aβ, tau and phosphorylated tau (p-tau). mRNA studies showed significant downregulation of only two of 84 AD-related genes, Apbb1 and Lrp1, at 4 h after irradiation, and of only one gene, Il1α, at 1 year after irradiation. Spatial learning ability and memory were not significantly affected at 1 or 2 years after irradiation. No induction of amyloid fibrillogenesis or changes in APP, Aβ, tau, or p-tau expression was detected at 4 months or 2 years after irradiation. TBI induced early or late transcriptional alteration in only a few AD-related genes but did not significantly affect spatial learning, memory or AD-like pathological change in mice.

  1. Peripherally administered sera antibodies recognizing amyloid-β oligomers mitigate Alzheimer's disease-like pathology and cognitive decline in aged 3× Tg-AD mice.

    PubMed

    Wang, Hai-Chao; Yu, Yun-Zhou; Liu, Si; Zhao, Meng; Xu, Qing

    2016-04-04

    Active and passive immunotherapy targeting amyloid-β (Aβ) may be the most promising strategy to prevent or treat Alzheimer's disease (AD). Previously, immunization with the recombinant 6Aβ15-T antigen generated robust anti-Aβ serum antibodies that strongly recognized Aβ42 oligomers in different mice, markedly reduced the amyloid burden, and improved behavioral performance of immunized older AD mice. Here, we further determined that these anti-6Aβ15-T serum antibodies from different strains of mice displayed anti-Aβ antibody responses against the same epitopes in the Aβ1-15 region. Peripheral administration of anti-6Aβ15-T serum antibodies was also effective to mitigate AD-like pathology and cognitive decline in aged 3× Tg-AD mice. Specifically, the levels of Aβ and tau in the brains of 3× Tg-AD mice were significantly reduced after passive immunotherapy, which seemed necessary or beneficial to ameliorate memory impairment. In addition, our results showed that this immunotherapy also prevented presynaptic dynamin 1 degradation, which might help to further protect synaptic functions and allow functional recovery of cognition. Moreover, immunization with 6Aβ15-T in rabbits induced a similar antibody response as that in mice, and the rabbit serum antibodies reacted strongly with Aβ42 oligomers and inhibited oligomer-mediated neurotoxicity. We concluded that passive immunization with Aβ42 oligomer conformation-sensitive anti-6Aβ15-T serum antibodies is effective in providing potentially therapeutic effects in aged 3× Tg-AD mice by reducing Aβ and tau.

  2. Agmatine ameliorates type 2 diabetes induced-Alzheimer's disease-like alterations in high-fat diet-fed mice via reactivation of blunted insulin signalling.

    PubMed

    Kang, Somang; Kim, Chul-Hoon; Jung, Hosung; Kim, Eosu; Song, Ho-Taek; Lee, Jong Eun

    2017-02-01

    The risk of Alzheimer's disease (AD) is higher in patients with type 2 diabetes mellitus (T2DM). Previous studies in high-fat diet-induced AD animal models have shown that brain insulin resistance in these animals leads to the accumulation of amyloid beta (Aβ) and the reduction in GSK-3β phosphorylation, which promotes tau phosphorylation to cause AD. No therapeutic treatments that target AD in T2DM patients have yet been discovered. Agmatine, a primary amine derived from l-arginine, has exhibited anti-diabetic effects in diabetic animals. The aim of this study was to investigate the ability of agmatine to treat AD induced by brain insulin resistance. ICR mice were fed a 60% high-fat diet for 12 weeks and received one injection of streptozotocin (100 mg/kg/ip) 4 weeks into the diet. After the 12-week diet, the mice were treated with agmatine (100 mg/kg/ip) for 2 weeks. Behaviour tests were conducted prior to sacrifice. Brain expression levels of the insulin signal molecules p-IRS-1, p-Akt, and p-GSK-3β and the accumulation of Aβ and p-tau were evaluated. Agmatine administration rescued the reduction in insulin signalling, which in turn reduced the accumulation of Aβ and p-tau in the brain. Furthermore, agmatine treatment also reduced cognitive decline. Agmatine attenuated the occurrence of AD in T2DM mice via the activation of the blunted insulin signal. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    PubMed

    Devi, L; Ohno, M

    2015-05-05

    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.

  4. Alzheimer's disease like pathology induced six weeks after aggregated amyloid-beta injection in rats: increased oxidative stress and impaired long-term memory with anxiety-like behavior.

    PubMed

    Sharma, Sheetal; Verma, Sonia; Kapoor, Monika; Saini, Avneet; Nehru, Bimla

    2016-09-01

    Amyloid-beta (Aβ) peptide deposition into insoluble plaques is a pathological hallmark of Alzheimer's disease (AD), but soluble oligomeric Aβ is considered to be more potent and has been hypothesized to directly impair learning and memory. Also, evidences from some clinical studies indicated that Aβ oligomer formation is the major cause for early AD onset. However, the biochemical mechanism involved in the oligomer-induced toxicity is not very well addressed. So, thise present study was undertaken to study the effects of single intracerebroventricular (icv) injection of protofibrillar Aβ 1-42 on the behavioral and biochemical profile in rats. Rats were divided into two groups (n = 8 per group): (1) sham control group and (2) Aβ 1-42 injected group. A single dose of protofibrillar Aβ 1-42 (5 ul) through icv injection was bilaterally administered into the dorsal hippocampus, while sham control animals were administered with 5 µl of vehicle. The results demonstrated that the protofibrillar Aβ significantly inhibited long-term memory retention and increased anxiety levels as shown by the behavioral studies. The amyloid deposits were present inside the brain even six weeks after injection as confirmed by thioflavin-T staining and the neurodegeneration induced by these deposits was confirmed by Nissl's staining in hippocampal and cortical regions. The amyloid aggregates induced reactive oxygen species (ROS) production, acetylcholinesterase activity, nitrite levels, lipid peroxidation, and inhibited antioxidant enzyme activity in hippocampus, cortex, and striatum regions of rat brain after six weeks. The present study indicated that protofibrillar Aβ 1-42 injection altered long term memory, induced anxiety-like behavior and also developed Alzheimer's disease like pathology in rats.

  5. Hepatologic considerations in patients with parenchymal liver disease undergoing surgery.

    PubMed

    Gholson, C F; Provenza, J M; Bacon, B R

    1990-05-01

    Patients with liver disease requiring surgical procedures are at increased perioperative risk. In addition, the deleterious effect of anesthesia on hepatocellular function, altered drug pharmacokinetics, aberrant hemostasis, postoperative encephalopathy and infection, with multiorgan failure, all contribute to perioperative morbidity and mortality. Although limited by the lack of widely accepted quantitative liver function tests, preoperative evaluation and risk assessment is imperative. Acute viral hepatitis, alcoholic hepatitis, refractory coagulopathy, Child's class C cirrhosis, and emergent surgery are major risk factors predictive of a poor outcome. In addition, elective abdominal surgical procedures should be avoided in potential candidates for orthotopic liver transplantation. Identification and correction of reversible risk factors via meticulous preoperative definition of the etiology, chronicity, and severity of the patient's liver disease within the confines of surgical urgency is the goal of the preoperative hepatology consultation.

  6. Periodontal and coronary heart disease in patients undergoing coronary angiography.

    PubMed

    Berent, Robert; Auer, Johann; Schmid, Peter; Krennmair, Gerald; Crouse, Stephen F; Green, John S; Sinzinger, Helmut; von Duvillard, Serge P

    2011-01-01

    Periodontal inflammation has been implicated in atherosclerosis and coronary heart disease (CHD). Coronary angiography (CA) is used in the assessment of CHD; only a few studies have evaluated periodontal disease (PD) and angiographic measures of coronary atherosclerosis. The aim of this study was to investigate the association between CHD and PD. In this prospective epidemiologic study, 466 patients underwent CA and were assessed for PD. All patients underwent physical, laboratory, cardiac, and dental examination including dental x-rays. Periodontal disease and coronary angiograms were evaluated blindly by a dentist and 2 cardiologists, respectively. A coronary stenosis greater than 50% was ruled as CHD. Periodontal disease was defined and measured with the Community Periodontal Index of Treatment Needs (CPITN); and if at least 2 sextants (segments dividing mandible and maxilla into 6) were recorded as having CPITN of at least 3 (signifying that sextant had periodontal pocket depth ≥ 3.5 mm), the patient was coded as having PD. Three-hundred forty-nine patients (74.9%) had CHD assessed by CA The CHD patients had PD in 55.6% vs 41.9% in the non-CHD patients (P < .01). The CPITN scores were significantly higher in patients with vs without CHD, 2.43 vs 2.16, respectively (P = .023). After adjusting for age, sex, and risk factors for atherosclerosis with additional inclusion of C-reactive protein and erythrocyte sedimentation rate, PD remained significantly related to CHD (odds ratio = 1.9; 95% confidence interval, 1.2-3.1). Other predictors for CHD were male sex, age, high-density lipoprotein cholesterol, and diabetes. Our results demonstrate an increased odds ratio for angiographically determined CHD in patients with PD and that CHD and PD may cluster in particular groups of a population. Our data indicate that PD represents a potentially modifiable risk factor that is both preventable and treatable with predictable treatments that pose negligible risk.

  7. Inflammatory bowel diseases activity in patients undergoing pelvic radiation therapy

    PubMed Central

    Seisen, Thomas; Klotz, Caroline; Mazeron, Renaud; Maroun, Pierre; Petit, Claire; Deutsch, Eric; Bossi, Alberto; Haie-Meder, Christine; Chargari, Cyrus; Blanchard, Pierre

    2017-01-01

    Background Few studies with contradictory results have been published on the safety of pelvic radiation therapy (RT) in patients with inflammatory bowel disease (IBD). Methods From 1989 to 2015, a single center retrospective analysis was performed including all IBD patients who received pelvic external beam radiation therapy (EBRT) or brachytherapy (BT) for a pelvic malignancy. Treatment characteristics, IBD activity and gastrointestinal (GI) toxicity were examined. Results Overall, 28 patients with Crohn’s disease (CD) (n=13) or ulcerative colitis (n=15) were included in the present study. Median follow-up time after irradiation was 5.9 years. Regarding IBD activity, only one and two patients experienced a severe episode within and after 6 months of follow-up, respectively. Grade 3/4 acute GI toxicity occurred in 3 (11%) patients, whereas one (3.6%) patient experienced late grade 3/4 GI toxicity. Only patients with rectal IBD location (P=0.016) or low body mass index (BMI) (P=0.012) experienced more severe IBD activity within or after 6 months following RT, respectively. Conclusions We report an acceptable tolerance of RT in IBD patients with pelvic malignancies. Specifically, a low risk of uncontrolled flare-up was observed. PMID:28280621

  8. 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

  9. Complications in patients with alcohol-associated liver disease who undergo liver transplantation.

    PubMed

    Gaglio, Paul J; Gaglio, Paul J

    2012-11-01

    Cirrhosis caused by alcohol-associated liver disease is a common indication for liver transplantation worldwide. Patients with alcohol-associated liver disease who undergo liver transplantation face multiple challenging comorbid medical issues that enhance the potential for perioperative and postoperative complications. Awareness of these issues and appropriate therapeutic intervention may minimize the negative effect of these complications on posttransplantation survival. This article reviews important posttransplantation problems in patients transplanted for alcohol-associated liver disease.

  10. 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

  11. Ethical aspects of undergoing a predictive genetic testing for Huntington's disease.

    PubMed

    Andersson, Petra Lilja; Juth, Niklas; Petersén, Åsa; Graff, Caroline; Edberg, Anna-Karin

    2013-03-01

    The aim of this study was to describe the experiences of undergoing a presymptomatic genetic test for the hereditary and fatal Huntington's disease, using a case study approach. The study was based on 18 interviews with a young woman and her husband from the decision to undergo the test, to receiving the results and trying to adapt to them, which were analysed using a life history approach. The findings show that the process of undergoing a presymptomatic test involves several closely connected ethical and medical questions, such as the reason for the test, the consequences of the test results and how health-care services can be developed to support people in this situation.

  12. Perioperative risk factors in patients with liver disease undergoing non-hepatic surgery

    PubMed Central

    Pandey, Chandra Kant; Karna, Sunaina Tejpal; Pandey, Vijay Kant; Tandon, Manish; Singhal, Amit; Mangla, Vivek

    2012-01-01

    The patients with liver disease present for various surgical interventions. Surgery may lead to complications in a significant proportion of these patients. These complications may result in considerable morbidity and mortality. Preoperative assessment can predict survival to some extent in patients with liver disease undergoing surgical procedures. A review of literature suggests nature and the type of surgery in these patients determines the peri-operative morbidity and mortality. Optimization of premorbid factors may help to reduce perioperative mortality and morbidity. The purpose of this review is to discuss the effect of liver disease on perioperative outcome; to understand various risk scoring systems and their prognostic significance; to delineate different preoperative variables implicated in postoperative complications and morbidity; to establish the effect of nature and type of surgery on postoperative outcome in patients with liver disease and to discuss optimal anaesthesia strategy in patients with liver disease. PMID:23494910

  13. Nutritional status and clinical outcome in postterm neonates undergoing surgery for congenital heart disease.

    PubMed

    Mitting, Rebecca; Marino, Luise; Macrae, Duncan; Shastri, Nitin; Meyer, Rosan; Pathan, Nazima

    2015-06-01

    Poor growth is a common complication in infants with congenital heart disease. There has been much focus on low birth weight as having increased risk of adverse outcomes following neonatal heart surgery. In this study, we examined whether preoperative nutritional status, measured by admission weight-for-age z score, was associated with postoperative clinical outcome. Retrospective case series. Pediatric Cardiac ICU at the Royal Brompton Hospital. Neonates undergoing surgery for congenital heart disease. Those undergoing ductus arteriosus ligation alone were excluded. Children with coexisting noncardiac morbidity were excluded. Outcome variables included prevalence of postoperative complications (including sepsis, delayed chest closure, renal impairment, and necrotizing enterocolitis), duration of ventilation, intensive care stay, postoperative mortality, and mortality at 1 year after surgery. None. Analysis of patient data only. Two hundred forty-eight neonates fulfilled the entry criteria. Median (interquartile range) age was 7 days (2-15 d), median (interquartile range) weight was 3.3 kg (2.91-3.6 kg), and median weight-for-age z score was -0.77 (-1.44 to 0.01). Twenty-eight children (11%) had a weight-for-age z score of less than -2. There was no evidence that children with lower weight-for-age z score had less severe surgery as measured by the Risk Adjustment for Congenital Heart Surgery 1 score. In multivariable regression analysis, the weight-for-age z at admission had strong correlation with the number of days free of respiratory support (invasive and noninvasive ventilation) at 28 days (p < 0.0001) and with all-cause mortality at 1 year (p = 0.001). Poor nutritional status as measured by weight-for-age z is associated with adverse short- and long-term outcomes in neonates undergoing surgery for congenital heart disease.

  14. Polygamy and Risk of Coronary Artery Disease in Men Undergoing Angiography: An Observational Study

    PubMed Central

    Lotfi, Amir; Al-Murayeh, Mushabab; Al-kaabi, Salem; Al-Faifi, Salem M.; Alama, Mohamed N.; Hersi, Ahmad S.; Dixon, Ciaran M.; Ahmed, Waleed; Al-Shehri, Mohamed; Youssef, Ali; Elimam, Ahmed Moustafa; Abougalambou, Ayman S.; Murad, Waheed; Alsheikh-Ali, Alawi A.

    2017-01-01

    Epidemiologic evidence suggests a link between psychosocial risk factors such as marital status and coronary artery disease (CAD). Polygamy (multiple concurrent wives) is a distinct marital status practiced in many countries in Asia and the Middle East, but its association with CAD is not well defined. We conducted a multicenter, observational study of consecutive patients undergoing coronary angiography during the period from April 1, 2013, to March 30, 2014. Of 1,068 enrolled patients, 687 were married men. Polygamy was reported in 32% of married men (1 wife: 68%, 2 wives: 19%, 3 wives: 10%, and 4 wives: 3%). When stratified by number of wives, significant baseline differences were observed in age, type of community (rural versus urban), prior coronary artery bypass grafting (CABG), and household income. After adjusting for baseline differences, there was a significant association between polygamy and CAD (adjusted OR 4.6 [95% CI 2.5, 8.3]), multivessel disease (MVD) (adjusted OR 2.6 [95% CI 1.8, 3.7]), and left main disease (LMD) (adjusted OR 3.5 [95% CI 2.1, 5.9]). Findings were consistent when the number of wives was analyzed as a continuous variable. In conclusion, among married men undergoing coronary angiography for clinical indications, polygamy is associated with the presence of significant CAD, MVD, and LMD. PMID:28250991

  15. Polygamy and Risk of Coronary Artery Disease in Men Undergoing Angiography: An Observational Study.

    PubMed

    Daoulah, Amin; Lotfi, Amir; Al-Murayeh, Mushabab; Al-Kaabi, Salem; Al-Faifi, Salem M; Elkhateeb, Osama E; Alama, Mohamed N; Hersi, Ahmad S; Dixon, Ciaran M; Ahmed, Waleed; Al-Shehri, Mohamed; Youssef, Ali; Elimam, Ahmed Moustafa; Abougalambou, Ayman S; Murad, Waheed; Alsheikh-Ali, Alawi A

    2017-01-01

    Epidemiologic evidence suggests a link between psychosocial risk factors such as marital status and coronary artery disease (CAD). Polygamy (multiple concurrent wives) is a distinct marital status practiced in many countries in Asia and the Middle East, but its association with CAD is not well defined. We conducted a multicenter, observational study of consecutive patients undergoing coronary angiography during the period from April 1, 2013, to March 30, 2014. Of 1,068 enrolled patients, 687 were married men. Polygamy was reported in 32% of married men (1 wife: 68%, 2 wives: 19%, 3 wives: 10%, and 4 wives: 3%). When stratified by number of wives, significant baseline differences were observed in age, type of community (rural versus urban), prior coronary artery bypass grafting (CABG), and household income. After adjusting for baseline differences, there was a significant association between polygamy and CAD (adjusted OR 4.6 [95% CI 2.5, 8.3]), multivessel disease (MVD) (adjusted OR 2.6 [95% CI 1.8, 3.7]), and left main disease (LMD) (adjusted OR 3.5 [95% CI 2.1, 5.9]). Findings were consistent when the number of wives was analyzed as a continuous variable. In conclusion, among married men undergoing coronary angiography for clinical indications, polygamy is associated with the presence of significant CAD, MVD, and LMD.

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. The frequency of cardiac arrests in patients with congenital heart disease undergoing cardiac catheterization.

    PubMed

    Odegard, Kirsten C; Bergersen, Lisa; Thiagarajan, Ravi; Clark, Laura; Shukla, Avinash; Wypij, David; Laussen, Peter C

    2014-01-01

    Cardiac catheterization for patients with congenital heart disease has shifted from diagnostic to predominantly interventional procedures because of advances in catheter-based technologies. Children undergoing therapeutic catheterization may be at higher risk of adverse events, and the purpose of our study was to determine the incidence of cardiac arrest (CA) in patients with congenital heart disease undergoing cardiac catheterization at a large pediatric tertiary referral center. All CAs from January 2004 through December 2009 occurring in the cardiac catheterization laboratory were reviewed. A CA was defined as an event in which cessation of circulation required chest compressions. Procedure, patient, practitioner, and system-related factors were examined. Over the study period, during 7289 catheterization procedures, 70 procedures were associated with a CA (0.96 [99% confidence interval, 0.7-1.3] per 100 procedures); 48 events (69%) were successfully resuscitated to a perfusing rhythm, 18 events (26%) resulted in need for extracorporeal membrane oxygenation, and 4 events (6%) resulted in unsuccessful resuscitation. Sudden onset of cardiac arrhythmia led to CA during 38 events (54%). The duration of resuscitation after CA was ≤11 minutes in 71%. Occurrence of CA was associated with interventional procedures (P < 0.001) and younger age (P < 0.001). A change in systems for scheduling and communication of cases was associated with a significant reduction in the incidence of CA (1.5% vs 0.7%; P = 0.002). The incidence of CA in children undergoing cardiac catheterization is high compared with pediatric noncardiac surgery. Procedural and system factors were associated with occurrence of CA in this cohort. These issues highlight the need for close communication, anticipation, and preparation.

  1. Perioperative Stroke in Infants Undergoing Open Heart Operations for Congenital Heart Disease

    PubMed Central

    Chen, Jodi; Zimmerman, Robert A.; Jarvik, Gail P.; Nord, Alex S.; Clancy, Robert R.; Wernovsky, Gil; Montenegro, Lisa M.; Hartman, Diane M.; Nicolson, Susan C.; Spray, Thomas L.; Gaynor, J. William; Ichord, Rebecca

    2010-01-01

    Background The prevalence of perioperative stroke in infants undergoing operations for congenital heart disease has not been well described. The objectives of this study were to determine the prevalence of stroke as assessed by postoperative brain magnetic resonance imaging (MRI), characterize the neuroanatomic features of focal ischemic injury, and identify risk factors for its development. Methods Brain MRI was performed in 122 infants 3 to 14 days after cardiac operation with cardiopulmonary bypass, with or without deep hypothermic circulatory arrest. Preoperative, intraoperative, and postoperative data were collected. Risk factors were tested by logistic regression for univariate and multivariate associations with stroke. Results Stroke was identified in 12 of 122 patients (10%). Strokes were preoperative in 6 patients and possibly intraoperative or postoperative in the other 6 patients, and were clinically silent except in 1 patient who had clinical seizures. Arterial-occlusive and watershed infarcts were identified with equal distribution in both hemispheres. Multivariate analysis identified lower birth weight, preoperative intubation, lower intraoperative hematocrit, and higher blood pressure at admission to the cardiac intensive care unit postoperatively as significant factors associated with stroke. Prematurity, younger age at operation, duration of cardiopulmonary bypass, and use of deep hypothermic circulatory arrest were not significantly associated with stroke. Conclusions The prevalence of stroke in infants undergoing operations for congenital heart disease was 10%, half of which occurred preoperatively. Most were clinically silent and undetected without neuroimaging. Mechanisms included thromboembolism and hypoperfusion, with patient-specific, procedure-specific, and postoperative contributions to increased risk. PMID:19699905

  2. Tuberculous spondylitis in patients with end-stage renal disease undergoing chronic hemodialysis therapy.

    PubMed

    Verettas, D J; Ververidis, A N; Boyiatzis, C; Panagoutsos, S; Galanis, V; Passadakis, P; Kazakos, K; Vargemezis, V

    2006-04-01

    Tuberculosis of the spine is not rare in immunocompromised patients and particularly in those with end-stage renal disease (ESRD). Furthermore, the possible vascular compromise of the spinal cord in patients with diabetic nephropathy may result in symptoms of neurological involvement that could lead to deterioration and paralysis. We report a series of 4 patients with ESRD undergoing dialysis that developed tuberculous spondylitis of the thoracic spine. Diabetic nephropathy was the primary cause for chronic kidney disease in 2 patients; 3 of these patients were treated conservatively with anti-tuberculous medication and orthotic splints and were cured. The fourth patient with diabetes mellitus and clinically evident signs and symptoms of severe vascular insufficiency has additionally developed incomplete paraplegia. A complete sensory recovery and partial recovery of the hip flexors and abductors within 3 months occurred, following decompression of the spine and drainage of the abscess, in combination with long-term anti-tuberculous treatment and spinal orthosis.

  3. Increased coronary artery disease severity in black women undergoing coronary bypass surgery.

    PubMed

    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

    2015-02-01

    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 P(trend) = 0.0021). A similar trend was not observed between black and white male CABG patients (adjusted P(trend) = 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.

  4. Impact of chronic obstructive pulmonary disease on patients undergoing laryngectomy for laryngeal cancer.

    PubMed

    Sylvester, Michael J; Marchiano, Emily; Park, Richard Chan Woo; Baredes, Soly; Eloy, Jean Anderson

    2017-02-01

    Although chronic obstructive pulmonary disease (COPD) is a common comorbidity in patients undergoing laryngeal cancer surgery, the impact of this comorbidity in this setting is not well established. In this analysis, we used the Nationwide Inpatient Sample (NIS) to elucidate the impact of COPD on outcomes after laryngectomy for laryngeal cancer. The NIS was queried for patients admitted from 1998 to 2010 with laryngeal cancer who underwent total or partial laryngectomy. Patient demographics, type of admission, length of stay, hospital charges, and concomitant diagnoses were analyzed. Our inclusion criteria yielded a cohort of 40,441 patients: 3,051 with COPD and 37,390 without. On average, COPD was associated with an additional $12,500 (P < 0.001) in hospital charges and an additional 1.4 days (P < 0.001) of hospital stay. There was no significant difference in incidence of in-hospital mortality between the COPD and non-COPD groups after total laryngectomy (1.1% in COPD vs. 1.0% in non-COPD; P = 0.776); however, there was an increased incidence of in-hospital mortality in the COPD group compared to the non-COPD group after partial laryngectomy (3.4% in COPD vs. 0.4% in non-COPD; P < 0.001). Multivariate adjusted logistic regression revealed that COPD was associated with greater odds of pulmonary complications after both partial laryngectomy (odds ratio [OR] = 3.198; P < 0.001) and total laryngectomy (OR = 1.575; P < 0.001). Chronic obstructive pulmonary disease appears to be associated with greater hospital charges, length of stay, and postoperative pulmonary complications in patients undergoing laryngectomy for laryngeal cancer. Chronic obstructive pulmonary disease after partial, but not total, laryngectomy appears to be associated with increased risk of in-hospital mortality. 2C. Laryngoscope, 2016 127:417-423, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  5. Instrument to assess educational programs for parents of children with congenital heart disease undergoing cardiac surgery.

    PubMed

    Pino Armijo, Paola; Ramírez León, Muriel; Clavería Rodríguez, Cristian

    2017-10-01

    To design and validate an instrument to assess the relevance of educational programs for parents of children with congenital heart disease (CHD) undergoing cardiac surgery. In October 2011, an instrument was designed based on Kaufman's model and on the bibliography, and a survey was developed in the form of a checklist with 32 close-ended questions about received education and desired education, categorized into 5 items: educator, time, place, means, and content. The survey was reviewed by 4 academic professionals and 9 experts in the care of children with CHD, and the checklist was extended to include 42 close-ended questions and 5 open questions. The instrument was administered on the day before discharge to the parents of children with CHD undergoing cardiac surgery at the Department of Pediatrics between February and August 2013. The survey was self-administered by the first participants and administered by the investigator among the remaining participants. Fifty-five children met inclusion criteria; a total of 60 parents took part in the study. Agreement was observed between received education and desired education, which was statistically significant only in terms of education provided by a cardiologist (p= 0.000, K= 0.659) and in the hall (p= 0.000, K= 0.655). Statistically significant differences were observed between the 19 self-administered surveys and the 41 surveys administered by the investigator. Among the latter, a greater level of completion was observed for all items. A validated instrument was developed to assess the relevance of educational programs for parents of children with CHD undergoing cardiac surgery. This survey should be administered by a health care provider for a better understanding of information.

  6. Pain and quality of life in patients undergoing radiotherapy for spinal metastatic disease treatment

    PubMed Central

    2013-01-01

    Background Radiotherapy is an important tool in the control of pain in patients with spinal metastatic disease. We aimed to evaluate pain and of quality of life of patients with spinal metastatic disease undergoing radiotherapy with supportive treatment. Methods The study enrolled 30 patients. From January 2008 to January 2010, patients selection included those treated with a 20 Gy tumour dose in five fractions. Patients completed the visual analogue scale for pain assessment and the SF-36 questionnaire for quality of life assessment. Results The most frequent primary sites were breast, multiple myeloma, prostate and lymphoma. It was found that 14 spinal metastatic disease patients (46.66%) had restricted involvement of three or fewer vertebrae, while 16 patients (53.33%) had cases involving more than three vertebrae. The data from the visual analogue scale evaluation of pain showed that the average initial score was 5.7 points, the value 30 days after the end of radiotherapy was 4.60 points and the average value 6 months after treatment was 4.25 points. Notably, this final value was 25.43% lower than the value from the initial analysis. With regard to the quality of life evaluation, only the values for the functional capability and social aspects categories of the questionnaire showed significant improvement. Conclusion Radiotherapy with supportive treatment appears to be an important tool for the treatment of pain in patients with spinal metastatic disease. PMID:23418821

  7. Assessment of Fatigue in End Stage Renal Disease Patients Undergoing Hemodialysis: Prevalence and Associated Factors

    PubMed Central

    Zyga, Sofia; Alikari, Victoria; Sachlas, Athanasios; Fradelos, Evangelos C.; Stathoulis, John; Panoutsopoulos, Georgios; Georgopoulou, Maria; Theophilou, Paraskeui; Lavdaniti, Maria

    2015-01-01

    Background: Fatigue is a common symptom referred by many patients undergoing hemodialysis. Fatigue is associated with poor health-related quality of life (HRQoL) and is an important predictor for survival of hemodialysis patients. Aim: To assess the levels of fatigue and demographic factors affecting it among patients with End Stage Renal Disease undergoing hemodialysis. Methods: This quantitative study was carried out in two Dialysis Units of Hospitals in Athens Region. Between January 2015 and June 2015, 129 hemodialysis patients completed the Greek Version of the Fatigue Assessment Scale (FAS). Demographic data of patients was recorded. For the statistical analysis IBM SPSS Statistics version 20 was used. Results: The mean FAS score was 24.99. 49 patients (38.0%) were non fatigued, 61 patients (47.3%) were fatigued, and 19 patients (13.7%) were extremely fatigued. Higher levels of fatigue were reported among hemodialysis patients residing in urban areas, in those with low educational level and unemployed. Conclusion: The findings of this study can be used in the assessment of fatigue and early identification of high-risk patients (especially of the unemployed, those who occupy with domestic works, those with low educational level and of urban citizens). Use of this knowledge by hemodialysis nurses may lead to a better understanding of the factors of fatigue in ESRD, which in turn may lead to a more effective treatment. PMID:26843728

  8. 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

  9. Hepatitis G virus in patients with cryptogenic liver disease undergoing liver transplantation.

    PubMed

    Pessoa, M G; Terrault, N A; Ferrell, L D; Kim, J P; Kolberg, J; Detmer, J; Collins, M L; Yun, A J; Viele, M; Lake, J R; Roberts, J P; Ascher, N L; Wright, T L

    1997-05-01

    To examine the prevalence of hepatitis G virus (HGV) in end-stage liver disease of unknown cause and the role of HGV infection in posttransplantation hepatitis, we studied 46 patients undergoing liver transplantation (mean age, 50 years; M:F, 18:28) with cryptogenic cirrhosis. HGV RNA was detected by polymerase chain reaction (PCR) and was quantified by a branched DNA (bDNA) assay. The prevalence of HGV RNA was determined in samples collected before and after liver transplantation and was found to be 22% and 67%, respectively. We evaluated the prevalence of posttransplantation hepatitis in 25 patients, 16 of whom were HGV-positive and 9 were HGV-negative. The proportion of patients with hepatitis was not significantly different in the two groups (38% in HGV-positive and 22% in HGV-negative patients). The median histological scores were significantly higher in liver biopsies from patients with HGV infection than in those without HGV infection (2 [range, 0-14] and 1 [range, 0-3]; P = .01), but the histological scores were low overall. The duration of follow-up was similar in the two groups. HGV RNA levels were not correlated with the severity of liver disease based on histological score (r = -.08). Graft survival and patient survival were not significantly different. We concluded that liver disease was frequent (32%) after transplantation in patients with a pretransplantation diagnosis of cryptogenic cirrhosis, although the disease was generally mild. Although HGV RNA was demonstrable in the majority (67%) of patients after transplantation, there was no relationship between the presence of HGV RNA and the presence of posttransplantation liver disease. The finding of posttransplantation hepatitis in the absence of known viruses (A-G), suggests that other, as-yet-unidentified viruses may be important.

  10. High Prevalence of Nonalcoholic Fatty Liver Disease in Adolescents Undergoing Bariatric Surgery.

    PubMed

    Xanthakos, Stavra A; Jenkins, Todd M; Kleiner, David E; Boyce, Tawny W; Mourya, Reena; Karns, Rebekah; Brandt, Mary L; Harmon, Carroll M; Helmrath, Michael A; Michalsky, Marc P; Courcoulas, Anita P; Zeller, Meg H; Inge, Thomas H

    2015-09-01

    Little is known about the prevalence of nonalcoholic fatty liver disease (NAFLD) among severely obese adolescents or factors that determine its development. We investigated the prevalence of NAFLD in a multicenter cohort of adolescents undergoing bariatric surgery and the factors associated with it. We enrolled 242 adolescents undergoing bariatric surgery between March 2007 and February 2012 at 5 tertiary care centers into a multicenter, prospective observational cohort study. Intraoperative core liver biopsies were collected from 165 subjects; 17 were excluded because of insufficient liver tissue or use of hepatotoxic medications, so 148 remained in the study (mean age, 16.8 ± 1.6 years; median body mass index = 52 kg/m(2)). Liver tissues were analyzed by histology using validated criteria. Hepatic gene expression was analyzed in 67 samples. NAFLD was present in 59% of this predominantly female (72%), white (68%), non-Hispanic (91%) cohort. Of subjects with NAFLD, 24% had borderline and 10% had definite nonalcoholic steatohepatitis (NASH). Mild fibrosis (stage 2 or lower) was observed in 18% of liver biopsies and stage 3 was observed in 0.7%, but cirrhosis was not detected. Dyslipidemia was present in 78% of subjects, hypertension in 44%, and diabetes in 14%. More severe NAFLD was associated with increasing levels of alanine aminotransferase, fasting glucose level, hypertension (each P < .01), and white blood cell count (P = .04). Only diabetes was associated with detection of fibrosis (odds ratio = 3.56; 95% confidence interval: 1.93-6.56). Microarray analysis associated presence of NASH with altered expression of genes that regulate macrophage chemotaxis, cholesterol absorption, and fatty acid binding. More than half of adolescents undergoing bariatric surgery in this cohort had NAFLD, yet the prevalence of severe or fibrotic NASH was low. Increasing severity of NAFLD was associated with level of alanine aminotransferase and cardiometabolic risk factors, but

  11. High Prevalence of Nonalcoholic Fatty Liver Disease in Adolescents Undergoing Bariatric Surgery

    PubMed Central

    Xanthakos, Stavra A.; Jenkins, Todd M.; Kleiner, David E.; Boyce, Tawny W.; Mourya, Reena; Karns, Rebekah; Brandt, Mary L.; Harmon, Carroll M.; Helmrath, Michael A.; Michalsky, Marc P.; Courcoulas, Anita P.; Zeller, Meg H.; Inge, Thomas H.

    2015-01-01

    Background & Aims Little is known about the prevalence of nonalcoholic fatty liver disease (NAFLD) among severely obese adolescents or factors that determine its development. We investigated the prevalence of NAFLD in a multicenter cohort of adolescents undergoing bariatric surgery and factors associated with it. Methods We enrolled 242 adolescents undergoing bariatric surgery between March 2007 and February 2012 at 5 tertiary care centers into a multicenter, prospective observational cohort study. Intra-operative core liver biopsies were collected from 165 subjects; 17 were excluded because of insufficient liver tissue or use of hepatotoxic medications, so 148 remained in the study (mean age 16.8±1.6 y old; median body mass index [BMI], 52 kg/m2). Liver tissues were analyzed by histology using validated criteria. Hepatic gene expression was analyzed in 67 samples. Results NAFLD was present in 59% of this predominantly female (72%), white (68%), non-Hispanic (91%) cohort. Of subjects with NAFLD, 24% had borderline and 10% had definite nonalcoholic steatohepatitis (NASH). Mild fibrosis (≤ stage 2) was observed in 18% of liver biopsies and stage 3 in 0.7%, but cirrhosis was not detected. Dyslipidemia was present in 78% of subjects, hypertension in 44%, and diabetes in 14%. More severe NAFLD was associated with increasing levels of alanine aminotransferase (ALT), fasting glucose level, hypertension (each P<.01) and white blood cell count (P=.04). Only diabetes was associated with detection of fibrosis (odds ratio, 3.56; 95% confidence interval, 1.93–6.56). Microarray analysis associated presence of NASH with altered expression of genes that regulate macrophage chemotaxis, cholesterol absorption, and fatty acid binding. Conclusions More than half of adolescents undergoing bariatric surgery in this cohort had NAFLD, yet the prevalence of severe or fibrotic NASH was low. Increasing severity of NAFLD was associated with level of ALT and cardio-metabolic risk factors

  12. Management of Pain and Quality of Life in Patients with Chronic Kidney Disease Undergoing Hemodialysis.

    PubMed

    Zyga, Sofia; Alikari, Victoria; Sachlas, Athanasios; Stathoulis, John; Aroni, Adamantia; Theofilou, Paraskevi; Panoutsopoulos, Georgios

    2015-10-01

    An important dimension that influences the quality of life of hemodialysis patients is the pain they experience. Quality of life and self-efficacy in pain can play an important role in chronic kidney disease and treatment outcomes. The purpose of the study was to examine self-efficacy in pain and quality of life among patients with end stage renal disease undergoing hemodialysis. Between April 2013 and June 2013, 224 hemodialysis patients completed the Missoula-VITAS Quality of Life Index-15 and the Pain Self-Efficacy Questionnaire. The study was conducted in four dialysis units in hospitals of the Peloponnese region. Sociodemographic data of patients and their individual medical history were recorded. Statistical analysis was performed using SPSS version 19. The more effective the self-efficacy in pain, the lower the quality of life enjoyed by hemodialysis patients. The majority of respondents described the overall quality of life as "moderate," while the self-efficacy in pain depended on comorbidity or complications that accompany the process of hemodialysis. The findings of this study can be used in the development and improvement of health services for the management of patients. Healthcare professionals should understand the concerns and treat the symptoms of patients that affect quality of life, providing thereby holistic health care.

  13. Outcomes in Patients With Hemophilia and von Willebrand Disease Undergoing Invasive or Surgical Procedures.

    PubMed

    Chapin, John; Bamme, Jaqueline; Hsu, Fraustina; Christos, Paul; DeSancho, Maria

    2017-03-01

    Adults with hemophilia A (HA), hemophilia B (HB), and von Willebrand disease (VWD) frequently require surgery and invasive procedures. However, there is variability in perioperative management guidelines. We describe our periprocedural outcomes in this setting. A retrospective chart review from January 2006 to December 2012 of patients with HA, HB, and VWD undergoing surgery or invasive procedures was conducted. Type of procedures, management including the use of continuous factor infusion, and administration of antifibrinolytics were reviewed. Adverse outcomes were defined as acute bleeding (<48 hours), delayed bleeding (≥48 hours), transfusion, inhibitor development, and thrombosis. We identified 59 patients with HA and HB. In all, 24 patients had severe hemophilia and 12 had mild/moderate hemophilia. Twelve patients had inhibitors. There were also 5 female carriers of HA and 6 patients with VWD. There were 34 major surgeries (26 orthopedic, 8 nonorthopedic) and 129 minor surgeries. Continuous infusion was used in 55.9% of major surgeries versus 8.5% of minor surgeries. Antifibrinolytics were administered in 14.7% of major surgeries versus 23.2% of minor surgeries. In all, 4 patients developed acute bleeding and 10 patients developed delayed bleeding. Delayed bleeding occurred in 28.6% of genitourinary procedures and in 16.1% of dental procedures. Five patients acquired an inhibitor and 2 had thrombosis. In conclusion, patients with HA, HB, or VWD had similar rates of adverse outcomes when undergoing minor surgeries or major surgeries. This finding underscores the importance of an interdisciplinary management and procedure-specific guidelines for patients with hemophilia and VWD prior to even minor invasive procedures.

  14. A comparative study of phosphate binders in patients with end stage kidney disease undergoing hemodialysis.

    PubMed

    Prajapati, Viken A; Galani, Varsha J; Shah, Pankaj R

    2014-05-01

    In the present study, a comparative evaluation of the effects of calcium acetate, calcium carbonate, sevelamer hydrochloride and lanthanum carbonate was carried out in 120 patients with end stage kidney disease (ESKD) undergoing hemodialysis. Biochemical parameters, like serum phosphorous, serum calcium and serum alkaline phosphatase level and intact parathyroid hormone level, were measured. A statistically significant reduction in serum phosphorous, serum calcium, calcium × phosphorous and serum alkaline phosphatase level were observed with all phosphate binders during 3 months of treatment. Reduction in serum phosphorous were observed with calcium acetate (1.5 mg/dL), calcium carbonate (1.3 mg/dL), sevelamer hydrochloride (2.1 mg/dL) and lanthanum carbonate (1.79 mg/dL). The reduction of serum alkaline phosphatase was observed more commonly with sevelamer (107.37 IU/L) and lanthanum (104.33 IU/L) treatments than with calcium acetate (93.9 IU/L) and calcium carbonate (86.57 IU/L). There was no statistically significant change in serum calcium observed with sevelamer and lanthanum treatments, while calcium-based phosphate binders caused a significant rise in the serum calcium level. Serum intact parathyroid hormone level was significantly reduced with all phosphate binder treatments. This decline was highest with sevelamer and lowest with calcium carbonate. All treatments were well tolerated and safety profiles were consistent with previous reports in hemodialysis patients. It is concluded that all phosphate binders are safe and effective for the treatment of hyperphosphatemia in patients with ESKD undergoing hemodialysis. However, sevelamer hydrochloride seems to be superior among all with lowering incidence of hypercalcemia.

  15. 7,8-Dihydroxyflavone, a Small Molecule TrkB Agonist, Improves Spatial Memory and Increases Thin Spine Density in a Mouse Model of Alzheimer Disease-Like Neuronal Loss

    PubMed Central

    Castello, Nicholas A.; Nguyen, Michael H.; Tran, Jenny D.; Cheng, David; Green, Kim N.; LaFerla, Frank M.

    2014-01-01

    Augmenting BDNF/TrkB signaling has been demonstrated to be a promising strategy for reversing cognitive deficits in preclinical models of Alzheimer disease (AD). Although these studies highlight the potential of targeting BDNF/TrkB signaling, this strategy has not yet been tested in a model that develops the disease features that are most closely associated with cognitive decline in AD: severe synaptic and neuronal loss. In the present study, we investigated the impact of 7,8-dihydroxyflavone (DHF), a TrkB agonist, in CaM/Tet-DTA mice, an inducible model of severe neuronal loss in the hippocampus and cortex. Systemic 7,8-DHF treatment significantly improved spatial memory in lesioned mice, as measured by water maze. Analysis of GFP-labeled neurons in CaM/Tet-DTA mice revealed that 7,8-DHF induced a significant and selective increase in the density of thin spines in CA1 of lesioned mice, without affecting mushroom or stubby spines. These findings suggest chronic upregulation of TrkB signaling with 7,8-DHF may be an effective and practical strategy for improving function in AD, even after substantial neuronal loss has occurred. PMID:24614170

  16. Cardiovascular risk factors and diseases in women undergoing hysterectomy with ovarian conservation

    PubMed Central

    Laughlin-Tommaso, Shannon K.; Khan, Zaraq; Weaver, Amy L.; Schleck, Cathy D.; Rocca, Walter A.; Stewart, Elizabeth A.

    2015-01-01

    Objective To study the association of preexisting cardiovascular risk factors and diseases in women who underwent hysterectomy with bilateral ovarian conservation compared with controls. Methods Using the Rochester Epidemiology Project records-linkage system, we identified all Olmsted County, Minnesota women who underwent hysterectomy with ovarian conservation between January 1, 1965 and December 31, 2002 (cases). Each case was aged-matched (±1 year) to a woman selected randomly who resided in the county and did not undergo hysterectomy or oophorectomy prior to the index date (date of hysterectomy in her matched case). Using electronic codes, we identified cardiovascular risk factors (diabetes, hypertension, hyperlipidemia, obesity, metabolic syndrome, and polycystic ovarian syndrome) and diseases (coronary artery disease, congestive heart failure, myocardial infarction, and stroke) that occurred before the index date. Analyses were stratified by age at hysterectomy and surgical indication. Results During the study period, 3,816 women underwent hysterectomy with ovarian conservation for a benign indication. Preexisting hyperlipidemia, obesity, and metabolic syndrome were significantly more frequent in cases than controls in univariable analyses. Obesity remained significantly associated in multivariable analyses overall, for nearly all age groups, and across all indications. Stroke was significantly more frequent in cases than controls in the women <36 years. Congestive heart failure and stroke were significantly less common in cases than controls in the women >50 years. Conclusions Hysterectomy with ovarian conservation is associated with cardiovascular risk factors, particularly obesity. Obesity may contribute to the underlying gynecologic conditions leading to hysterectomy; however, surgical selection may also play a role. PMID:26173076

  17. Should hepatic metastatic colorectal cancer patients with extrahepatic disease undergo liver resection/ablation?

    PubMed

    Byam, Jerome; Reuter, Nathaniel P; Woodall, Charles E; Scoggins, Charles R; McMasters, Kelly M; Martin, Robert C G

    2009-11-01

    Surgical therapy has been proven to be the mainstay of treatment for hepatic metastases from colorectal cancer (CRM) in the appropriate patient. Previous contraindications were patients with extrahepatic disease (EHD) do not benefit from liver resection or ablation. We hypothesized that the survival of patients with EHD who receive aggressive multimodality care would be the same as those without EHD. A review of our 1305 patient prospective hepato-pancreatico-biliary database from August 1995 to April 2008 identified 383 patients with surgical management of metastatic CRM to the liver. A total of 39 patients with limited EHD underwent liver resection/ablation vs 344 patients without EHD. There were no significant differences in hepatic disease burden (mean clinical risk score of 2.3 and 2.1 in patients with and without EHD, P=.19, and median number of hepatic metastases of 2 in each group, P=.88) or size of the largest lesion (mean 4.6 vs 4.5 cm with and without EHD, P=.84). EHD consisted of lung metastases in 33%, nodal metastases in 21%, peritoneal in 15%, unknown in 15%, and other in 15%. There was no difference in patients with and without EHD undergoing surgical with resection only in 41% vs 48%, ablation only in 31% vs 30%, and combined resection and ablation in 28% vs 22% (P=.61). Overall survival in patients with EHD was not significantly different (median survival 24 vs 33 months, P=.06). A thorough understanding of the biology of disease and appropriate multimodality care can lead to improved survival in patients with EHD, when compared with chemotherapy alone.

  18. Incidence of abdominal wall hernias in patients undergoing aortic surgery for aneurysm or occlusive disease.

    PubMed

    Papadimitriou, D; Pitoulias, G; Papaziogas, B; Koutsias, S; Vretzakis, G; Argiriadou, H; Papaziogas, T

    2002-05-01

    The aim of this study was to compare the incidence of abdominal and incisional hernias in patients with abdominal aortic aneurysm (AAA) versus patients with aortoiliac occlusive disease (AOD). The study included retrospectively 121 patients, who underwent elective aortic surgery due to AAA (n = 63) or AOD (n = 58) in the period between January 1998 and January 2000. The patients were examined for the presence of abdominal hernias upon admission, as well as for the development of incisional hernias on follow-up. The incidence of inguinal hernias was significantly higher in the group AAA (21/6-33.3%) compared to the group with AOD (6/58-10.3%) (p < 0.01). The incidence of other abdominal wall hernias (umbilical, epigastric or miscellaneous hernias) was also significant higher in AAA group. Furthermore, the incidence of inguinal hernias was significantly higher in the subgroup of patients with an aneurysm diameter more than 6 cm (41.5% vs 18.2%, p < 0.05). The mean follow-up of the patients was 1.7 +/- 0.3 years. 7 cases of incisional hernia were noted in the AAA group (11.1%) and only 2 cases in the AOD group (3.4%) (p < 0.05). The size of the aneurysm had no influence on the incidence of incisional hernias in the AAA group. We conclude that there seems to be an increased incidence of abdominal wall hernias as well as postoperative incisional hernias in patients undergoing aortic surgery for aneurysm disease compared with aortoiliac occlusive disease.

  19. 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

  20. Synthesis of multi-lactose-appended β-cyclodextrin and its cholesterol-lowering effects in Niemann–Pick type C disease-like HepG2 cells

    PubMed Central

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

    2017-01-01

    Niemann–Pick type C (NPC) disease, characterized by intracellular accumulation of unesterified cholesterol and other lipids owing to defects in two proteins NPC1 and NPC2, causes neurodegeneration and other fatal neurovisceral symptoms. Currently, treatment of NPC involves the use of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD). HP-β-CD is effective in the treatment of hepatosplenomegaly in NPC disease, albeit at a very high dose. One of the methods to reduce the required dose of HP-β-CD for treatment of NPC is to actively targeting hepatocytes with β-cyclodextrin (β-CD). The aim of the present study was to synthesize a novel multi-lactose-appended β-CD (multi-Lac-β-CD) and to evaluate its cholesterol-lowering effect in U18666A-treated HepG2 (NPC-like HepG2) cells. Further, the study aimed at delivering β-CD to hepatocytes via cholesterol-accumulated HepG2 cells, and indicated that the newly synthesized multi-Lac-β-CD had an average degree of substitution of lactose (DSL) of 5.6. This newly synthesized multi-Lac-β-CD was found to significantly decrease the concentration of intracellular cholesterol with negligible cytotoxicity as compared to HP-β-CD. An increased internalization of TRITC-multi-Lac-β-CD (DSL 5.6) as compared to TRITC-HP-β-CD was observed in NPC-like HepG2 cells. Further, the dissociation constant of peanut lectin with multi-Lac-β-CD (DSL5.6) was found to be extremely low (2.5 × 10−8 M). These results indicate that multi-Lac-β-CD (DSL5.6) diminished intracellular cholesterol levels in NPC-like HepG2 cells via asialoglycoprotein receptor (ASGPR)-mediated endocytosis. PMID:28179943

  1. Synthesis of multi-lactose-appended β-cyclodextrin and its cholesterol-lowering effects in Niemann-Pick type C disease-like HepG2 cells.

    PubMed

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

    2017-01-01

    Niemann-Pick type C (NPC) disease, characterized by intracellular accumulation of unesterified cholesterol and other lipids owing to defects in two proteins NPC1 and NPC2, causes neurodegeneration and other fatal neurovisceral symptoms. Currently, treatment of NPC involves the use of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD). HP-β-CD is effective in the treatment of hepatosplenomegaly in NPC disease, albeit at a very high dose. One of the methods to reduce the required dose of HP-β-CD for treatment of NPC is to actively targeting hepatocytes with β-cyclodextrin (β-CD). The aim of the present study was to synthesize a novel multi-lactose-appended β-CD (multi-Lac-β-CD) and to evaluate its cholesterol-lowering effect in U18666A-treated HepG2 (NPC-like HepG2) cells. Further, the study aimed at delivering β-CD to hepatocytes via cholesterol-accumulated HepG2 cells, and indicated that the newly synthesized multi-Lac-β-CD had an average degree of substitution of lactose (DSL) of 5.6. This newly synthesized multi-Lac-β-CD was found to significantly decrease the concentration of intracellular cholesterol with negligible cytotoxicity as compared to HP-β-CD. An increased internalization of TRITC-multi-Lac-β-CD (DSL 5.6) as compared to TRITC-HP-β-CD was observed in NPC-like HepG2 cells. Further, the dissociation constant of peanut lectin with multi-Lac-β-CD (DSL5.6) was found to be extremely low (2.5 × 10(-8) M). These results indicate that multi-Lac-β-CD (DSL5.6) diminished intracellular cholesterol levels in NPC-like HepG2 cells via asialoglycoprotein receptor (ASGPR)-mediated endocytosis.

  2. 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

  3. Role of Endoplasmic Reticulum Stress in Learning and Memory Impairment and Alzheimer's Disease-Like Neuropathology in the PS19 and APP(Swe) Mouse Models of Tauopathy and Amyloidosis.

    PubMed

    Briggs, Denise Isabelle; Defensor, Erwin; Memar Ardestani, Pooneh; Yi, Bitna; Halpain, Michelle; Seabrook, Guy; Shamloo, Mehrdad

    2017-01-01

    Emerging evidence suggests that endoplasmic reticulum (ER) stress may be involved in the pathogenesis of Alzheimer's disease (AD). Recently, pharmacological modulation of the eukaryotic translation initiation factor-2 (eIF2α) pathway was achieved using an integrated stress response inhibitor (ISRIB). While members of this signaling cascade have been suggested as potential therapeutic targets for neurodegeneration, the biological significance of this pathway has not been comprehensively assessed in animal models of AD. The present study investigated the ER stress pathway and its long-term modulation utilizing in vitro and in vivo experimental models of tauopathy (MAPT P301S)PS19 and amyloidosis (APP(Swe)). We report that thapsigargin induces activating transcription factor-4 (ATF4) in primary cortical neurons (PCNs) derived from rat and APP(Swe) nontransgenic (nTg) and transgenic (Tg) mice. ISRIB mitigated the induction of ATF4 in PCNs generated from wild-type (WT) but not APP(Swe) mice despite partially restoring thapsigargin-induced translational repression in nTg PCNs. In vivo, C57BL/6J and PS19 mice received prolonged, once-daily administration of ISRIB. While the compound was well tolerated by PS19 and C57BL/6J mice, APP(Swe) mice treated per this schedule displayed significant mortality. Thus, the dose was reduced and administered only on behavioral test days. ISRIB did not improve learning and memory function in APP(Swe) Tg mice. While ISRIB did not reduce tau-related neuropathology in PS19 Tg mice, no evidence of ER stress-related dysfunction was observed in either of these Tg models. Taken together, the significance of ER stress and the relevance of these models to the etiology of AD require further investigation.

  4. Excessive S-Adenosyl-L-Methionine-Dependent Methylation Increases Levels of Methanol, Formaldehyde and Formic Acid in Rat Brain Striatal Homogenates: Possible role in S-adenosyl-L-methionine-induced Parkinson’s disease-like disorders

    PubMed Central

    Lee, Eun-Sook; Chen, Hongtao; Hardman, Chadwick; Simm, Anthony; Charlton, Clivel

    2009-01-01

    Aims Excessive methylation may be a precipitating factor for Parkinson’s disease (PD) since S-adenosylmethionine (SAM), the endogenous methyl donor, induces PD-like changes when injected into the rat brain. The hydrolysis of the methyl ester bond of the methylated proteins produces methanol. Since methanol is oxidized into formaldehyde, and formaldehyde into formic acid in the body, we investigated the effects of SAM on the production of methanol, formaldehyde and formic acid in rat brain striatal homogenates and the toxicity of these products in PC12 cells. Main methods radio-enzymatic and colorimetric assays, cell viability, Western blot. Key findings SAM increased the formation of methanol, formaldehyde and formic acid in a concentration and time-dependent manner. Concentrations of [3H-methyl]-SAM at 0.17, 0.33, 0.67 and 1.34 nM produced 3.8, 8.0, 18.3 and 34.4 fmol/mg protein/h of [3H] methanol in rat striatal homogenates, respectively. SAM also significantly generated formaldehyde and formic acid in striatal homogenates. Formaldehyde was the most toxic metabolite to differentiated PC12 pheochromocytoma cells in cell culture studies, indicating that formaldehyde formed endogenously may contribute to neuronal damage in excessive methylation conditions. Subtoxic concentration of formaldehyde decreased the expression of tyrosine hydroxylase, the limiting factor in dopamine synthesis. Formaldehyde was more toxic to catecholaminergic PC12 cells than C6 glioma cells, indicating that neurons are more vulnerable to formaldehyde than glia cells. Significance We suggest that excessive carboxylmethylation of proteins might be involved in the SAM-induced PD-like changes and in the aging process via the toxic effects of formaldehyde. PMID:18930743

  5. 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. © The Author(s) 2015.

  6. The management of perioperative nutrition in patients with end stage liver disease undergoing liver transplantation

    PubMed Central

    Zhang, Qi-Kun

    2015-01-01

    Malnutrition is found in almost 100% of patients with end stage liver disease (ESLD) awaiting transplantation and malnutrition before transplantation leads to higher rates of post-transplant complications and worse graft survival outcomes. Reasons for protein energy malnutrition include several metabolic alterations such as inadequate intake, malabsorption, and overloaded expenditure. And also, stress from surgery, gastrointestinal reperfusion injury, immunosuppressive therapy and corticosteriods use lead to delayed bowl function recovery and disorder of nutrients absorption. In the pretransplant phase, nutritional goals include optimization of nutritional status and treatment of nutrition-related symptoms induced by hepatic decompensation. During the acute post-transplant phase, adequate nutrition is required to help support metabolic demands, replenish lost stores, prevent infection, arrive at a new immunologic balance, and promote overall recovery. In a word, it is extremely important to identify and correct nutritional deficiencies in this population and provide an adequate nutritional support during all phases of liver transplantation (LT). This study review focuses on prevalence, nutrition support, evaluation, and management of perioperative nutrition disorder in patients with ESLD undergoing LT. PMID:26605281

  7. The management of perioperative nutrition in patients with end stage liver disease undergoing liver transplantation.

    PubMed

    Zhang, Qi-Kun; Wang, Meng-Long

    2015-10-01

    Malnutrition is found in almost 100% of patients with end stage liver disease (ESLD) awaiting transplantation and malnutrition before transplantation leads to higher rates of post-transplant complications and worse graft survival outcomes. Reasons for protein energy malnutrition include several metabolic alterations such as inadequate intake, malabsorption, and overloaded expenditure. And also, stress from surgery, gastrointestinal reperfusion injury, immunosuppressive therapy and corticosteriods use lead to delayed bowl function recovery and disorder of nutrients absorption. In the pretransplant phase, nutritional goals include optimization of nutritional status and treatment of nutrition-related symptoms induced by hepatic decompensation. During the acute post-transplant phase, adequate nutrition is required to help support metabolic demands, replenish lost stores, prevent infection, arrive at a new immunologic balance, and promote overall recovery. In a word, it is extremely important to identify and correct nutritional deficiencies in this population and provide an adequate nutritional support during all phases of liver transplantation (LT). This study review focuses on prevalence, nutrition support, evaluation, and management of perioperative nutrition disorder in patients with ESLD undergoing LT.

  8. Preventing radiocontrast-induced nephropathy in chronic kidney disease patients undergoing coronary angiography

    PubMed Central

    Hung, Yao-Min; Lin, Shoa-Lin; Hung, Shih-Yuan; Huang, Wei-Chun; Wang, Paul Yung-Pou

    2012-01-01

    Radiocontrast-induced nephropathy (RCIN) is an acute and severe complication after coronary angiography, particularly for patients with pre-existing chronic kidney disease (CKD). It has been associated with both short- and long-term adverse outcomes, including the need for renal replacement therapy, increased length of hospital stay, major cardiac adverse events, and mortality. RCIN is generally defined as an increase in serum creatinine concentration of 0.5 mg/dL or 25% above baseline within 48 h after contrast administration. There is no effective therapy once injury has occurred, therefore, prevention is the cornerstone for all patients at risk for acute kidney injury (AKI). There is a small but growing body of evidence that prevention of AKI is associated with a reduction in later adverse outcomes. The optimal strategy for preventing RCIN has not yet been established. This review discusses the principal risk factors for RCIN, evaluates and summarizes the evidence for RCIN prophylaxis, and proposes recommendations for preventing RCIN in CKD patients undergoing coronary angiography. PMID:22655164

  9. Does chronic kidney disease affect the mortality rate in patients undergoing spine surgery?

    PubMed

    Bains, Ravi S; Kardile, Mayur; Mitsunaga, Lance; Chen, Yuexin; Harris, Jessica; Paxton, Elizabeth; Majid, Kamran

    2017-09-01

    The number of patients with chronic kidney disease (CKD) and their life expectancy has been increasing. With time number of patients undergoing spine surgery has also been on a rise. This study we did a retrospective review of registry data to investigate the mortality rate of chronic kidney disease patients following spine surgery using a large, multi-center spine registry. 12,276 consecutive spine-fusion patients from January 2009 to December 2012 were included and mortality rates in patients with CKD compared to those with normal kidney function following spine surgery. Logistic regression was usedto evaluate risk of mortality following spine surgery. The average age of the cohort was 59 (SD=13.4). 53% were female. Patients who had stage 3, 4 or 5 CKD were older than non-CKD patients (mean=71,SD=9.2 vs. 59, SD=13.3). After adjusting for confounding variables, patients with stage 3 or 4 CKD had higher mortality rates than patients with normal kidney function (OR 1.78, 95% CI 1.3-2.45) Hemodialysis-dependent patients (stage 5 CKD) had even higher rates of mortality compared to patients with normal function (OR 4.18, 95% CI1.87-9.34). our findings suggest that spine surgery is associated with significantly higher mortality rates in patients with CKD compared to patients with normal kidney function. Understanding the additional morbidity and mortality of spine surgery in this medically complicated group of patients is imperative for accurate preoperative risk assessment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Interaction of ApoE3 and ApoE4 isoforms with an ITM2b/BRI2 mutation linked to the Alzheimer disease-like Danish dementia: Effects on learning and memory.

    PubMed

    Biundo, Fabrizio; Ishiwari, Keita; Del Prete, Dolores; D'Adamio, Luciano

    2015-12-01

    Mutations in Amyloid β Precursor Protein (APP) and in genes that regulate APP processing--such as PSEN1/2 and ITM2b/BRI2--cause familial dementia, such Familial Alzheimer disease (FAD), Familial Danish (FDD) and British (FBD) dementias. The ApoE gene is the major genetic risk factor for sporadic AD. Three major variants of ApoE exist in humans (ApoE2, ApoE3, and ApoE4), with the ApoE4 allele being strongly associated with AD. ITM2b/BRI2 is also a candidate regulatory node genes predicted to mediate the common patterns of gene expression shared by healthy ApoE4 carriers and late-onset AD patients not carrying ApoE4. This evidence provides a direct link between ITM2b/BRI2 and ApoE4. To test whether ApoE4 and pathogenic ITM2b/BRI2 interact to modulate learning and memory, we crossed a mouse carrying the ITM2b/BRI2 mutations that causes FDD knocked-in the endogenous mouse Itm2b/Bri2 gene (FDDKI mice) with human ApoE3 and ApoE4 targeted replacement mice. The resultant ApoE3, FDDKI/ApoE3, ApoE4, FDDKI/ApoE4 male mice were assessed longitudinally for learning and memory at 4, 6, 12, and 16-17 months of age. The results showed that ApoE4-carrying mice displayed spatial working/short-term memory deficits relative to ApoE3-carrying mice starting in early middle age, while long-term spatial memory of ApoE4 mice was not adversely affected even at 16-17 months, and that the FDD mutation impaired working/short-term spatial memory in ApoE3-carrying mice and produced impaired long-term spatial memory in ApoE4-carrying mice in middle age. The present results suggest that the FDD mutation may differentially affect learning and memory in ApoE4 carriers and non-carriers.

  11. Detection of bacterial antigens and Alzheimer's disease-like pathology in the central nervous system of BALB/c mice following intranasal infection with a laboratory isolate of Chlamydia pneumoniae.

    PubMed

    Little, Christopher S; Joyce, Timothy A; Hammond, Christine J; Matta, Hazem; Cahn, David; Appelt, Denah M; Balin, Brian J

    2014-01-01

    Pathology consistent with that observed in Alzheimer's disease (AD) has previously been documented following intranasal infection of normal wild-type mice with Chlamydia pneumoniae (Cpn) isolated from an AD brain (96-41). In the current study, BALB/c mice were intranasally infected with a laboratory strain of Cpn, AR-39, and brain and olfactory bulbs were obtained at 1-4 months post-infection (pi). Immunohistochemistry for amyloid beta or Cpn antigens was performed on sections from brains of infected or mock-infected mice. Chlamydia-specific immunolabeling was identified in olfactory bulb tissues and in cerebrum of AR-39 infected mice. The Cpn specific labeling was most prominent at 1 month pi and the greatest burden of amyloid deposition was noted at 2 months pi, whereas both decreased at 3 and 4 months. Viable Cpn was recovered from olfactory bulbs of 3 of 3 experimentally infected mice at 1 and 3 months pi, and in 2 of 3 mice at 4 months pi. In contrast, in cortical tissues of infected mice at 1 and 4 months pi no viable organism was obtained. At 3 months pi, only 1 of 3 mice had a measurable burden of viable Cpn from the cortical tissues. Mock-infected mice (0 of 3) had no detectable Cpn in either olfactory bulbs or cortical tissues. These data indicate that the AR-39 isolate of Cpn establishes a limited infection predominantly in the olfactory bulbs of BALB/c mice. Although infection with the laboratory strain of Cpn promotes deposition of amyloid beta, this appears to resolve following reduction of the Cpn antigen burden over time. Our data suggest that infection with the AR-39 laboratory isolate of Cpn results in a different course of amyloid beta deposition and ultimate resolution than that observed following infection with the human AD-brain Cpn isolate, 96-41. These data further support that there may be differences, possibly in virulence factors, between Cpn isolates in the generation of sustainable AD pathology.

  12. Intraoperative Diagnosis of Anderson-Fabry Disease in Patients With Obstructive Hypertrophic Cardiomyopathy Undergoing Surgical Myectomy.

    PubMed

    Cecchi, Franco; Iascone, Maria; Maurizi, Niccolò; Pezzoli, Laura; Binaco, Irene; Biagini, Elena; Fibbi, Maria Laura; Olivotto, Iacopo; Pieruzzi, Federico; Fruntelata, Ana; Dorobantu, Lucian; Rapezzi, Claudio; Ferrazzi, Paolo

    2017-08-09

    Diagnostic screening for Anderson-Fabry cardiomyopathy (AFC) is performed in the presence of specific clinical red flags in patients with hypertrophic cardiomyopathy (HCM) older than 25 years. However, left ventricular outflow tract obstruction (LVOTO) has been traditionally considered an exclusion criteria for AFC. To examine a series of patients diagnosed with HCM and severe basal LVOTO undergoing myectomy in whom the diagnosis of AFC was suspected by the cardiac surgeon intraoperatively and confirmed by histological and genetic examinations. This retrospective analysis of patients undergoing surgical septal reduction strategies was conducted in 3 European tertiary referral centers for HCM from July 2013 to December 2016. Patients with a clinical diagnosis of obstructive HCM referred for surgical management of LVOTO were observed for at least 18 months after the procedure (mean [SD] follow-up, 33 [14] months). Etiology of patients with HCM who underwent surgical myectomy. From 2013, 235 consecutive patients with a clinical diagnosis of HCM underwent septal myectomy. The cardiac surgeon suspected a storage disease in 3 patients (1.3%) while inspecting their heart samples extracted from myectomy. The mean (SD) age at diagnosis for these 3 patients was 42 (4) years; all were male. None of the 3 patients presented with extracardiac features suggestive of AFC. All patients showed asymmetrical left ventricular hypertrophy, with maximal left ventricular thickness in the basal septum (19-31 mm), severe basal LVOTO (70-120 mm Hg), and left atrial dilatation (44-57 mm). Only 1 patient presented with late gadolinium enhancement on cardiovascular magnetic resonance at the right ventricle insertion site. The mean (SD) age at surgical procedure was 63 (5) years. On tactile sensation, the surgeon felt a spongy consistency of the surgical samples, different from the usual stony-elastic consistency typical of classic HCM, and this prompted histological examinations. Histology

  13. Short-term central venous catheter complications in patients with sickle cell disease who undergo apheresis.

    PubMed

    Yeral, Mahmut; Boga, Can; Oguzkurt, Levent; Asma, Suheyl; Kasar, Mutlu; Kozanoglu, Ilknur

    2014-01-01

    Patients with sickle cell disease (SCD) are prone to develop thrombosis and infection due to their inflammatory and immune deficiency state. These patients require red cell exchange therapy for treatment or prevention of hemoglobin S associated complications. Owing to vascular access problems, adult patients need central venous catheterization (CVC) for exchange procedures. Procedure related complications have been reported for long-term CVCs in pediatric patients. However, short-term CVC complications in adult patients are not clear. This report represents the results of documented complications of short-term CVCs in patients with SCD who undergo apheresis. A total of 142 non-tunneled catheters with average median diameter of 9 F (range 8-16 F) were implanted for apheresis. The catheters were mainly inserted through the right internal jugular vein (66.2 %). Total days of catheter were 412. Results were reported as a complication rate and event according to 1,000 catheter days and compared to a control group including 37 healthy stem cell donors. In the patient group, 1 (1 %) hematoma and 1 (1 %) infection were observed for internal jugular vein catheterization (3.7 hemorrhages and 3.7 infections according to 1,000 catheter days), whereas four (8.9 %) cases of thrombosis and 1 (2.2 %) infection (27 and 6.9 according to 1,000 catheter days) developed in femoral vein. There was a significant difference in terms of thrombosis (P = 0.009). In the control group, only individual developed thrombosis in internal jugular vein. Short-term CVC inserted through to the internal jugular vein seems to be safer than femoral vein in patients with SCD.

  14. Growth of children with end-stage renal disease undergoing daily hemodialysis.

    PubMed

    de Camargo, Maria Fernanda Carvalho; Henriques, Cristina Lucia; Vieira, Simone; Komi, Shirlei; Leão, Eliseth Ribeiro; Nogueira, Paulo Cesar Koch

    2014-03-01

    The aim of this report is to describe the effect of daily hemodialysis on the growth of children with end-stage renal disease (ESRD). We performed a prospective, observational study on 24 children with ESRD undergoing daily hemodialysis (DHD). The control group comprised 26 children on concurrent conventional hemodialysis (CHD), and the follow-up for both groups was 9.3 ± 3.0 months. No patient received growth hormone (GH) therapy. At the onset of the study, the height-for-age Z-score was -2.12 ± 1.54 in the CHD group and -2.84 ± 2.27 in the DHD group (p = 0.313). Assuming an increase of 0.5 standard deviation scores (SDS) of the height-for-age parameter as an improvement of growth, there were 33 % of patients in the DHD group and 8 % in the CHD group (p = 0.035). The cumulative probability of gain in height for age at 12 months was 40 % in the DHD group versus 15 % in the CHD group (p = 0.047). Also, 98 % of patients in the DHD group had an adequate total caloric intake, whereas 38 % in the CHD group reached this goal (p < 0.001). No patient left the study due to intensification of the dialysis modality. Our data show that the DHD favored a 0.5 SDS height gain in a third of patients without GH treatment. Dialysis intensification was not a cause for treatment dropouts, and DHD should be considered as a treatment for selected cases, especially small children.

  15. Clinical Experience With Penile Traction Therapy Among Men Undergoing Collagenase Clostridium histolyticum for Peyronie Disease.

    PubMed

    Ziegelmann, Matthew J; Viers, Boyd R; Montgomery, Brian D; Avant, Ross A; Savage, Joshua B; Trost, Landon W

    2017-06-01

    To evaluate the outcomes in men undergoing collagenase Clostridium histolyticum (CCH) with concurrent penile traction therapy (PTT) for the treatment of Peyronie disease (PD). We identified patients treated with CCH between March 2014 and July 2016. Patients were recommended to perform modeling and PTT between injection series. A final curve assessment was performed after patients completed CCH. A prospective database was maintained, including patient-reported frequency and duration of PTT. Statistical analysis was performed to evaluate outcomes based on use and duration of PTT. A total of 51 patients completed CCH and had complete objective data available for analysis. Mean (standard deviation [SD]) baseline curvature was 66.7 (25.0) degrees, and mean (SD) improvement post CCH was 20.9 (17.3) degrees (P < .0001). Thirty-five (69%) men reported daily PTT for a mean (SD) of 9.8 (6.3) hours per week. No significant difference was identified in the degree of curve improvement based on frequency or duration of PTT (P = .40). Similarly, no associations between PTT and functional outcomes including intercourse restoration and surgery prevention were identified. Stretched penile length increased nonsignificantly by a mean (SD) of +0.4 (1.5) cm in the PTT group, compared with -0.35 (1.5) in the non-PTT group (P = .21). The current series represents a "true-to-life" experience, wherein utilization patterns, attrition, and compliance issues are relevant factors impacting efficacy. PTT use with the Andropenis declined in both frequency and duration with subsequent injection series, and there was no significant difference in curve improvement or stretched penile length with a mean 10 hours of weekly concurrent PTT. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Effect of misoprostol on patients with aspirin-exacerbated respiratory disease undergoing aspirin challenge and desensitization.

    PubMed

    Walters, Kristen M; Simon, Ronald A; Woessner, Katharine M; Wineinger, Nathan E; White, Andrew A

    2017-07-01

    Prostaglandin E2 (PGE2) is an anti-inflammatory compound that inhibits 5-lipoxygenase activity. Diminished PGE2 regulation in aspirin-exacerbated respiratory disease (AERD) leads to respiratory reactions on cyclooxygenase 1 inhibition. In vitro studies have found that exogenous PGE2 stabilizes inflammatory mediator release. To examine whether misoprostol (oral prostaglandin E1 analogue) use during aspirin challenge and desensitization might decrease the severity of aspirin-induced symptoms and make desensitization safer for patients with AERD. Forty-five patients undergoing aspirin challenge and/or desensitization were randomized to misoprostol (n = 30) or placebo (n = 15) and compared with a group of historical controls (n = 31). Misoprostol (200 μg) was administered at 30 minutes, 90 minutes, and 4 hours after the first dose of nasal ketorolac. Measured end points included change in forced expiratory volume in 1 second (FEV1), peak nasal inspiratory flow rate (PNIF), number of treatments received for induced reactions, and adverse gastrointestinal effects. A difference in FEV1 and PNIF reduction was detected between misoprostol and placebo (P = .03) and misoprostol and historical controls (P = .01), respectively, during nasal ketorolac challenge. No difference was detected among aspirin reactors. Among all reactors, no difference in magnitude was found for FEV1 (P = .13) or PNIF (P = .07) reduction across all 3 groups. Total treatment requirement was similar (P = .14). Patients receiving misoprostol were more likely to report adverse gastrointestinal effects (P = .02). The addition of misoprostol to current aspirin challenge and/or desensitization protocols reveals no protective effect in reducing the intensity of nonsteroidal anti-inflammatory drug-induced symptoms and is not recommended based on the findings in this study. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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

    PubMed

    Rasiah, Rajah; Yusoff, Khalid; Mohammadreza, Amiri; Manikam, Rishya; Tumin, Makmor; Chandrasekaran, Sankara Kumar; Khademi, Shabnam; Bakar, Najmin Abu

    2013-09-25

    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. 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. 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. 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 at all, specific ones should be focused

  18. Interventions for prophylaxis of hepatic veno-occlusive disease in people undergoing haematopoietic stem cell transplantation.

    PubMed

    Cheuk, Daniel K L; Chiang, Alan K S; Ha, Shau Yin; Chan, Godfrey C F

    2015-05-27

    Hepatic veno-occlusive disease (VOD) is a severe complication after haematopoietic stem cell transplantation (HSCT). Different drugs with different mechanisms of action have been tried in HSCT recipients to prevent hepatic VOD. However, it is uncertain whether high-quality evidence exists to support any prophylactic therapy. We aimed to determine the effects of various prophylactic therapies on the incidence of hepatic VOD, overall survival, mortality, quality of life (QOL), and the safety of these therapies in people undergoing HSCT. We searched the Cochrane Central Registe of Controlled Trials (CENTRAL), MEDLINE, EMBASE, conference proceedings of three international haematology-oncology societies and two trial registries in January 2015, together with reference checking, citation searching and contact with study authors to identify additional studies. We included randomised controlled trials (RCTs) comparing prophylactic therapies with placebo or no treatment, or comparing different therapies for hepatic VOD in people undergoing HSCT. We used standard methodological procedures expected by Cochrane. We included 14 RCTs. Four trials (612 participants) compared ursodeoxycholic acid with or without additional treatment versus placebo or no treatment or same additional treatment. Two trials (259 participants) compared heparin with no treatment. Two trials (106 participants) compared low molecular weight heparin (LMWH) with placebo or no treatment. One trial (360 participants) compared defibrotide with no treatment. One trial (34 participants) compared glutamine with placebo. Two trials (383 participants) compared fresh frozen plasma (FFP) with or without additional treatment versus no treatment or same additional treatment. One trial (30 participants) compared antithrombin III with heparin versus heparin. One trial compared heparin (47 participants) with LMWH (46 participants) and prostaglandin E1 (PGE1) (47 participants). No trial investigated the effects of

  19. Severe nutritional risk predicts decreased long-term survival in geriatric patients undergoing pancreaticoduodenectomy for benign disease.

    PubMed

    Sanford, Dominic E; Sanford, Angela M; Fields, Ryan C; Hawkins, William G; Strasberg, Steven M; Linehan, David C

    2014-12-01

    Weight loss and malnutrition are poorly tolerated by geriatric patients, and pancreaticoduodenectomy (PD) can result in chronic malabsorption and weight loss. We sought to determine how preoperative severe nutritional risk (SNR), as defined by the American College of Surgeons National Surgical Quality Improvement Program/American Geriatric Society Best Practice Guidelines, affects long-term survival after PD for benign disease among geriatric and nongeriatric patients. All patients undergoing PD for nonmalignant conditions at a single center between 1995 and 2013 were followed for survival, excluding patients who died within 90 days of surgery. Survival of geriatric (age ≥65 years) and nongeriatric (age <65 years) patients with and without SNR was compared using Kaplan Meier methods. Cox regression was performed. There were 320 patients who underwent PD for benign disease. Over the course of the study, the proportion of geriatric patients undergoing PD for benign conditions increased from 25% to 46%. In addition to being older, geriatric patients undergoing PD for benign disease were significantly more likely to have coronary artery disease (CAD) and hypertension. Geriatric patients with preoperative SNR had significantly decreased long-term survival after PD for benign disease (p < 0.001), with roughly 1 in 3 patients dead at 5 years compared with 1 in 14 patients without SNR. Survival was not significantly different among nongeriatric patients with and without SNR. In geriatric patients, age, CAD, and SNR were significantly associated with decreased survival on both univariate and multivariate analysis. Severe nutritional risk can be a useful predictor of long-term survival in geriatric patients undergoing PD, and could improve patient risk stratification preoperatively. Nonoperative management should be strongly considered in geriatric patients with SNR, when malignancy is not suspected. Copyright © 2014 American College of Surgeons. Published by Elsevier Inc

  20. 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

  1. ACTH- and Cortisol-Associated Neutrophil Modulation in Coronary Artery Disease Patients Undergoing Stent Implantation

    PubMed Central

    Keresztes, Margit; Horváth, Tamás; Ocsovszki, Imre; Földesi, Imre; Serfőző, Gyöngyi; Boda, Krisztina; Ungi, Imre

    2013-01-01

    Background Psychosocial stress and activation of neutrophil granulocytes are increasingly recognized as major risk factors of coronary artery disease (CAD), but the possible relationship of these two factors in CAD patients is largely unexplored. Activation of neutrophils was reported to be associated with stenting; however, the issue of neutrophil state in connection with percutaneous coronary intervention (PCI) is incompletely understood from the aspect of stress and its hypothalamic-pituitary-adrenal axis (HPA) background. Thus, we aimed to study cortisol- and ACTH-associated changes in granulocyte activation in patients undergoing PCI. Methodology/Principal Findings Blood samples of 21 stable angina pectoris (SAP) and 20 acute coronary syndrome (ACS) patients were collected directly before (pre-PCI), after (post-PCI) and on the following day of PCI (1d-PCI). Granulocyte surface L-selectin, CD15 and (neutrophil-specific) lactoferrin were analysed by flow cytometry. Plasma cortisol, ACTH, and lactoferrin, IL-6 were also assayed. In both groups, pre- and post-PCI ratios of lactoferrin-bearing neutrophils were relatively high, these percentages decreased substantially next day; similarly, 1d-PCI plasma lactoferrin was about half of the post-PCI value (all p≤0.0001). Post-PCI ACTH was reduced markedly next day, especially in ACS group (SAP: p<0.01, ACS: p≤0.0001). In ACS, elevated pre-PCI cortisol decreased considerably a day after stenting (p<0.01); in pre-PCI samples, cortisol correlated with plasma lactoferrin (r∼0.5, p<0.05). In 1d-PCI samples of both groups, ACTH showed negative associations with the ratio of lactoferrin-bearing neutrophils (SAP: r = −0.601, p<0.005; ACS: r = −0.541, p<0.05) and with plasma lactoferrin (SAP: r = −0.435, p<0.05; ACS: r = −0.609, p<0.005). Conclusions/Significance Pre- and post-PCI states were associated with increased percentage of activated/degranulated neutrophils indicated by elevated lactoferrin

  2. Post-Operative Outcomes in Children With and Without Congenital Heart Disease Undergoing Noncardiac Surgery.

    PubMed

    Faraoni, David; Zurakowski, David; Vo, Daniel; Goobie, Susan M; Yuki, Koichi; Brown, Morgan L; DiNardo, James A

    2016-02-23

    Significant advances have been made in the diagnosis and treatment of children with congenital heart disease (CHD), allowing for longer life expectancies and an increasing number who will require noncardiac surgery. This study sought to compare the incidence of mortality and major adverse post-operative outcomes following noncardiac surgery in children with and without CHD. Data from the 2012 pediatric database of the American College of Surgeons National Surgical Quality Improvement Program were analyzed. After propensity score matching, and stratification by severity of CHD, mortality and adverse post-operative outcomes were compared between controls and children with CHD. Among the 51,008 children included in the database, 4,520 children with CHD underwent noncardiac surgery. After propensity score matching, we included 2,805 children with minor CHD, 1,272 with major CHD, and 417 with severe CHD. Children in each subgroup were matched and compared with controls without CHD who underwent noncardiac surgery of comparable complexity. The incidence of overall mortality was significantly higher in children with moderate (3.9%) and severe (8.2%) CHD compared with their controls (respectively, 1.7% [p < 0.001] and 1.2% [p = 0.001]). Both 30-day and overall mortality were significantly increased in children with severe CHD (odds ratio [OR]: 8.43, 95% confidence interval [CI]: 2.52 to 28.21; p < 0.001; OR: 7.32, 95% CI: 2.83 to 18.90; p < 0.001) compared with their matched controls. Overall mortality was also significantly increased in children with major CHD compared with their controls (OR: 2.28; 95% CI: 1.37 to 3.79; p = 0.002), whereas no difference was observed between children with minor CHD and their matched controls. Children with major and severe CHD, undergoing noncardiac surgery, have an increased risk of mortality compared with children without CHD. Further studies need to identify the optimal environment for surgical procedures, develop trained

  3. [Consistency analysis between preoperative CT enterography and intraoperative findings in patients undergoing surgery for Crohn's disease].

    PubMed

    Yang, Jianbo; Gong, Jianfeng; Li, Yi; Gu, Lili; Zhu, Weiming; Li, Jieshou

    2017-05-25

    To evaluate the diagnostic value of preoperative CT enterography (CTE) on obstruction, fistula and abscess formation compared to intraoperative findings in patients undergoing surgery for Crohn's disease(CD), aiming to provide reference to clinical practice. Preoperative CTE data of 176 CD patients confirmed by clinic, endoscopy, imaging, operation and pathology at the Department of General Surgery in Nanjing Jinling Hospital from January 2013 to December 2015 were enrolled in retrospective cohort study. All the patients underwent enhanced full abdominal CT scan using SIMENS SOMATOM Definition Flash 64 row dual-source CT machine. CTE scans were performed from the dome of diaphragm to the symphysis pubis. The CT images in arterial and venous phase were reconstructed with 1.0 mm thin layer, and then processed in MMWP 4.0 workstation including multi-planar recombination, surface recombination and maximum density projection. The sensitivity, specificity, positive and negative predictive value, false negative rate and accuracy of preoperative CTE on obstruction, fistula and abscess were compared with intraoperative findings. Among 176 patients, 122 were males and 54 were females with median age of 29 (18 to 65) years, median disease duration of 48 (1 to 240) months, median time interval from CT scan to operation of 16(1 to 30) days, and median body mass index of 17.8 (10.8 to 34.7) kg/m(2). Twenty-six cases (14.8%) had nutritional risk (NRS2002≥3); 23 cases (13.1%) had lesions limited to ileum; 19 cases (10.8%) had lesions limited to colon; 126 cases (71.6%) had simultaneous lesions of ileum and colon, and 8 cases (4.5%) had lesion in upper gastrointestinal tract. A total of 199 lesions of small intestine were identified by preoperative CTE, including 131 of obstruction (65.8%), 42 of fistula (21.1%), and 26 of abscess (13.1%), while 235 lesions were confirmed by operation, including 133 of obstruction (56.6%), 74 of fistula (31.5%), 28 of abscess (11.9%). The

  4. Prevalence of clinical and subclinical middle ear disease in cats undergoing computed tomographic scans of the head.

    PubMed

    Shanaman, Miriam; Seiler, Gabriela; Holt, David E

    2012-01-01

    Three hundred and ten cats that had CT imaging of the head between January 2000 and December 2007 were evaluated retrospectively. Data that were recorded included signalment, presenting complaint, clinical signs, presence of upper respiratory tract disease, and CT findings. One hundred and one cats had evidence of middle ear disease on CT. Thirty-four of the 101 cats (34%) did not have a primary complaint of ear-related disease, clinical signs or physical findings consistent with ear disease, suggesting that the middle ear disease was subclinical. Twenty-seven of the 34 cats (79%) had concurrent nasal disease. Middle ear lesions were chronic in appearance. With the exception of tympanic bulla lysis, CT findings were similar in cats presenting with primary aural disease versus cats with presumptive subclinical middle ear disease. The majority of the cats did not return for treatment of the identified middle ear abnormalities. Subclinical middle ear disease is relatively frequent in cats undergoing CT imaging of the head. Few cats required subsequent treatment for ear disease although follow up was limited. Identification of subclinical middle ear abnormalities on CT should prompt acquisition of a detailed patient history and bilateral otoscopic examination.

  5. Is Nottingham Health Profile a reliable tool to measure quality of life of Filipinos with chronic kidney diseases undergoing hemodialysis.

    PubMed

    Chuku, Chika Lawson; Valdez, Josephine R; Ajonuma, Louis Chukwuemeka

    2010-12-01

    The quality of life (QOL) of hemodialysis patients is often compromised and many tools have been developed to assess the health-related QOL of chronic kidney disease (CKD) patients undergoing hemodialysis. However, no such tool is currently in use in the Philippines. The objective of this study is to determine if Nottingham Health Profile (NHP) can be a useful tool in the Philippines. Eighty patients undergoing hemodialysis in the dialysis unit of our hospital were enrolled for this study. Sixty-nine patients completed the study. Comparative analysis revealed significant difference in social isolation with favorable result for the Filipino patients. Other measures correlate well although with differences that were not statistically significant. NHP can be successfully applied as a standard QOL tool in the Philippines. However, it should be translated into Filipino to avoid language difficulty. NHP may be recommended for QOL determination in other developing countries.

  6. Mitral valve disease in patients with Marfan syndrome undergoing aortic root replacement.

    PubMed

    Kunkala, Meghana R; Schaff, Hartzell V; Li, Zhuo; Volguina, Irina; Dietz, Harry C; LeMaire, Scott A; Coselli, Joseph S; Connolly, Heidi

    2013-09-10

    Cardiac manifestations of Marfan syndrome include aortic root dilation and mitral valve prolapse (MVP). Only scant data exist describing MVP in patients with Marfan syndrome undergoing aortic root replacement. We retrospectively analyzed data from 166 MFS patients with MVP who were enrolled in a prospective multicenter registry of patients who underwent aortic root aneurysm repair. Of these 166 patients, 9% had mitral regurgitation (MR) grade >2, and 10% had MR grade 2. The severity of MVP and MR was evaluated by echocardiography preoperatively and ≤ 3 years postoperatively. Forty-one patients (25%) underwent composite graft aortic valve replacement, and 125 patients (75%) underwent aortic valve-sparing procedures; both groups had similar prevalences of MR grade >2 (P=0.7). Thirty-three patients (20%) underwent concomitant mitral valve (MV) intervention (repair, n=29; replacement, n=4), including all 15 patients with MR grade >2. Only 1 patient required MV reintervention during follow-up (mean clinical follow-up, 31 ± 10 months). Echocardiography performed 21 ± 13 months postoperatively revealed MR >2 in only 3 patients (2%). One early death and 2 late deaths occurred. Although the majority of patients with Marfan syndrome who undergo elective aortic root replacement have MVP, only 20% have concomitant MV procedures. These concomitant procedures do not seem to increase operative risk. In patients with MR grade ≤ 2 who do not undergo a concomitant MV procedure, the short-term incidence of progressive MR is low; however, more follow-up is needed to determine whether patients with MVP and MR grade ≤ 2 would benefit from prophylactic MV intervention.

  7. Prevalence of chronic kidney disease and anemia in patients with coronary artery disease with normal serum creatinine undergoing percutaneous coronary interventions: relation to New York Heart Association class.

    PubMed

    Malyszko, Jolanta; Bachorzewska-Gajewska, Hanna; Malyszko, Jacek; Levin-Iaina, Nomy; Iaina, Adrian; Dobrzycki, Slawomir

    2010-08-01

    Kidney disease and cardiovascular disease seem to be lethally synergistic and both are approaching the epidemic level. A reduced glomerular filtration rate is associated with increased mortality risk in patients with heart failure. Many patients with congestive heart failure are anemic. Anemia is very often associated with chronic kidney disease. To assess--in relation to New York Heart Association class--the prevalence of anemia and chronic kidney disease in patients with normal serum creatinine in a cohort of 526 consecutive patients with coronary artery disease undergoing percutaneous coronary interventions. GFR was estimated using the simplified MDRD formula, the Cockcroft-Gault formula, the Jeliffe and the novel CKD-EPI formula. According to the WHO definition the prevalence of anemia in our study was 21%. We observed a progressive decline in GFR and hemoglobin concentration together with a rise in NYHA class. Significant correlations were observed between eGFR and systolic blood pressure, diastolic blood pressure, age, NYHA class, complications of PCI, including bleeding, and major adverse cardiac events. The prevalence of anemia and chronic kidney disease is high in patients undergoing PCI despite normal serum creatinine, particularly in higher NYHA class. Lower eGFR and hemoglobin are associated with more complications, including bleeding after PCI and higher prevalence of major adverse cardiac events. In patients with risk factors for cardiovascular disease, GFR should be estimated since renal dysfunction and subsequent anemia are important risk factors for cardiovascular morbidity and mortality.

  8. 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.

  9. Surgical outcomes in patients with chronic obstructive pulmonary disease undergoing abdominal operations: An analysis of 331,425 patients.

    PubMed

    Fields, Adam C; Divino, Celia M

    2016-04-01

    Chronic obstructive pulmonary disease (COPD) affects >15 million individuals in the United States and is a common comorbidity in patients undergoing surgery; therefore, the association between COPD in patients and postoperative surgical outcomes was investigated. The objective of this study was to assess the associations between COPD and postoperative morbidity, mortality, and hospital duration of stay. Patients who underwent cholecystectomy, appendectomy, small bowel resection, partial colectomy, hepatic resection, gastrectomy, pancreatectomy, and ventral hernia repair with and without COPD (n = 331,425) in the National Surgical Quality Improvement Program database from 2007 to 2010 were studied. The primary outcomes were 30-day morbidity, mortality, and hospital duration of stay; secondary outcomes were specific postoperative complications. COPD was present in 12,491 patients (3.8%) undergoing the abdominal operations surveyed. The 30-day morbidity and mortality rates and hospital duration of stay for patients undergoing all abdominal procedures reviewed was greater for patients with COPD compared with patients without COPD (all P < .0001, except hepatic resection). Multivariate analysis controlling for comorbidities revealed that COPD was associated independently with increased postoperative morbidity in all abdominal procedures reviewed, increased postoperative mortality after cholecystectomy, appendectomy, small bowel resection, and ventral hernia repair, and increased duration of stay after cholecystectomy, small bowel resection, partial colectomy, gastrectomy, pancreatectomy, and ventral hernia repair (all P < .05). Patients with COPD undergoing operative procedures in the abdomen have increased morbidity, mortality, and duration of stay. This study highlights the importance of studying potential preoperative optimization of pulmonary status in patients with COPD before operation. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Comparison of Symptoms, Treatment and Outcomes of Coronary Artery Disease among Rheumatoid Arthritis and Matched Subjects Undergoing Percutaneous Coronary Intervention

    PubMed Central

    Desai, Sonali P.; Januzzi, James L.; Pande, Ashvin N.; Pomerantsev, Eugene V.; Resnic, Frederic S.; Fossel, Anne; Chibnik, Lori B.; Solomon, Daniel H.

    2010-01-01

    Objective Rheumatoid arthritis (RA) is associated with an increased prevalence of coronary artery disease (CAD). We investigated the presenting symptoms of CAD, coronary anatomy (single vs. multivessel CAD), and treatment among a group of subjects undergoing percutaneous coronary intervention (PCI) with angioplasty and/or stenting. Methods We evaluated a retrospective cohort of 43 RA subjects and 43 matched non-RA subjects undergoing PCI at 2 academic referral centers. RA subjects were matched to non-RA subjects on age, gender, history of coronary artery bypass grafting (CABG), date of PCI and Interventional Cardiologist. We compared cardiac risk factors, presentation, treatment and outcomes. Results The mean age of the study cohort was 71 ± 10 years, and the distribution of traditional cardiac risk factors was similar in the subjects with RA compared to the matched non-RA subjects (all P values > 0.05). Seventy-four percent of subjects with RA compared to 67% of those without RA presented with an acute coronary syndrome prior to PCI (P = 0.48). All subjects in this cohort undergoing PCI had at least one stenosis in a major epicardial vessel and similar percentages of subjects with RA (44%) and without RA (40%) had multivessel CAD (P = 0.66). The administration of cardiac medications both at PCI and at hospital discharge was not different among subjects with RA compared to matched non-RA subjects. Conclusions Among this cohort with significant CAD undergoing PCI, clinical characteristics, presentation, severity of CAD, treatment modalities and outcomes were similar in subjects with RA and well-matched non-RA subjects. PMID:20541791

  11. Management of concomitant coronary artery disease in patients undergoing transcatheter aortic valve implantation: the United Kingdom TAVI Registry.

    PubMed

    Snow, Thomas M; Ludman, Peter; Banya, Winston; DeBelder, Mark; MacCarthy, Philip M; Davies, Simon W; Di Mario, Carlo; Moat, Neil E

    2015-11-15

    The management and impact of concomitant coronary artery disease in patients referred for TAVI remains contentious. We describe the prevalence, clinical impact and management of coronary artery disease (CAD) in patients in the United Kingdom TAVI Registry. All-inclusive study of patients undergoing TAVI in the United Kingdom (excluding Northern Ireland) from January 2007 to December 2011. Coronary artery disease at the time of TAVI was demonstrated on invasive angiography. 2588 consecutive patients were entered in the U.K. TAVI Registry. CAD was reported in 1171 pts with left main stem involvement in 12.4% of this cohort (n=145). Most patients were free of chest pain, but limited by dyspnoea (NYHA Class III & IV 81.9%). Angina was however more prevalent in those patients with CAD (p<0.0001). Hybrid PCI was uncommon, performed in only 14.7% of the CAD cohort (n=172). Survival at 30days, 1year, and 4years was 93.7%, 81.4% and 72.0% respectively. Adjusting for confounders in a multivariate model the presence and extent of CAD was not associated with early (30-days, p=0.36) or late (4years, p=0.10) survival. This contemporary study of coronary artery disease management in an "all-comers" patient population undergoing TAVI demonstrates that whilst often an indicator of significant underlying comorbidity coronary artery disease is not associated with decreased short or long-term survival. The majority of patients with aortic stenosis and concomitant CAD can be managed effectively by TAVI alone. However, the importance of the Heart Team in making decisions on individual patients must not be underestimated. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Assessment of Residual Disease With Molecular Breast Imaging in Patients Undergoing Neoadjuvant Therapy: Association With Molecular Subtypes.

    PubMed

    Menes, Tehillah S; Golan, Orit; Vainer, Gilead; Lerman, Hedva; Schneebaum, Schlomo; Klausner, Joseph; Even-Sapir, Einat

    2016-10-01

    Assessment of residual disease after neoadjuvant therapy for breast cancer is an ongoing challenge of breast imaging. This study evaluates the accuracy of a novel dedicated system for molecular breast imaging (MBI) composed of the new generation of cadmium zinc telluride detectors in assessing residual disease after neoadjuvant therapy in patients with breast cancer. Clinical data, imaging, surgical, and pathological findings of 51 women with breast cancer undergoing neoadjuvant therapy were recorded. MBI findings were correlated with surgical pathology results. Accuracy of MBI in predicting complete pathological response and size of residual disease was assessed according to molecular subtypes. The size of the largest focus of uptake on MBI correlated with the largest dimension measured on pathology (r = 0.55; P < .001). This correlation was stronger for triple negative and HER2/neu positive subtypes (r = 0.92 and 0.62, respectively). Sixteen patients (31%) had complete pathological response. The sensitivity and specificity of MBI for detecting residual disease were 83% (95% confidence interval [CI], 66-93) and 69% (95% CI, 42-88), respectively. For triple negative or HER2/neu positive disease the sensitivity and specificity were 88% (95% CI, 62-98) and 75% (95% CI, 43-93), respectively. The accuracy of MBI in assessing residual disease after neoadjuvant treatment might be related to the molecular subtype. Accuracy is highest in the triple negative and HER2/neu positive subtypes. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. The efficacy of low-dose tadalafil in patients undergoing hemodialysis with end-stage renal disease.

    PubMed

    Bolat, Mustafa Suat; Özer, İsmail; Cinar, Onder; Akdeniz, Ekrem; Aşcı, Ramazan

    2017-11-01

    Erectile dysfunction (ED) is a disorder that is frequently observed in people with chronic kidney disease who undergo hemodialysis (HD). In the context of evidence-based medicine, we aimed to investigate the effect of low-dose tadalafil on sexual function in patients undergoing HD. The medical records of 30 males (aged 29-65 years) with end-stage renal disease (ESRD) on a HD program, and who had received 5 mg tadalafil twice weekly, were retrospectively evaluated. Changes in erectile and ejaculatory function were evaluated using the International Erectile Function Index questionnaire, the Erection Hardness Scale (EHS), and the Male Sexual Health Questionnaire (MSHQ). The mean age of the patients was 47.6 ± 10.1 years, their mean body mass index was 24.3 ± 4.2 kg/m(2), their mean hemoglobin was 11.9 ± 0.9 g/dL, and their mean creatinine clearance was 5.8 ± 1.1 mL/min. At the third month of treatment, 36.6% of the patients had no ED, 40% had mild ED, 10% had mild-to-moderate ED, and 13.3% had moderate ED. The mean MSHQ scores (p < .05) and the mean EHS scores (p = .001) were significantly improved. There was no significant difference between Beck's Depression Inventory scores (p > .05), but Hamilton anxiety rate scores decreased significantly (p = .001). The quality-of-life score improved throughout the study period (p < .05). Tadalafil therapy is an effective therapeutic option in patients with ESRD who undergo HD, not only for the treatment of ED, but also for ejaculatory function, with acceptable adverse effects.

  14. Predictors of coronary artery disease in middle-aged Taiwanese women at premenopause, postmenopause and after undergoing hysterectomy.

    PubMed

    Tsai, Ching-Ching; Hsieh, Ming-Hsiung; Yang, Hung-Yu; Chan, Paul; Jeng, Chii

    2016-09-01

    To examine the predictors of coronary artery disease among middle-aged women at various menopausal statuses. Few studies have explored coronary artery disease predictors among middle-aged women at various menopausal statuses, particularly with the inclusion of women who underwent a hysterectomy. A cross-sectional design was adopted. Two hundred and twenty-five middle-aged women who were waiting for catheterisation examinations because of possible coronary artery disease were selected. These patients were divided into premenopausal (n = 41), postmenopausal (n = 143) and women who had undergone a hysterectomy groups (n = 41). The differences in the risk factors for coronary artery disease between patients with coronary artery disease (catheterisation results showing stenosis of >50% in at least one major coronary artery) and those without coronary artery disease in the three groups were compared. The participants were aged 56·8 ± 5·9 years. In the premenopausal group, the odds of coronary artery disease among ever or current smokers was 8·46 times the odds of coronary artery disease for the never smokers. In the postmenopausal group, the odds of coronary artery disease among diabetes patients was 2·89 times the odds of coronary artery disease for those without diabetes. Each additional point on the Chinese Beck Depression Inventory-II increased the risk of coronary artery disease by 5%. In the hysterectomy group, each additional increase in 1 mmHg in systolic blood pressure increased the risk of coronary artery disease by 4%. Smoking, diabetes, depression and systolic blood pressure are predictors of coronary artery disease in middle-aged women at premenopause, postmenopause and after undergoing hysterectomy respectively. These results are beneficial for middle-aged women at various menopausal stages to effectively implement prevention of coronary artery disease. These findings were among women being evaluated for possible coronary artery disease, we

  15. 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.

  16. Heart rate and outcome in patients with cardiovascular disease undergoing major noncardiac surgery.

    PubMed

    Biccard, B M

    2008-07-01

    There is an increasing awareness that an elevated resting heart rate is associated with increased all-cause mortality in the general population and that this may be an independent coronary risk factor This review was undertaken to determine whether heart rate is predictive of increased mortality and major morbidity in noncardiac surgical patients and whether heart rate manipulation improves perioperative outcome. A search of Medline from 1966 until October 2007 was conducted using the terms "heart rate", "surgery", "cardiac", "morbidity", "mortality" and "perioperative". The main findings were that an elevated perioperative heart rate, an absolute increase in heart rate and heart rate lability are independent predictors of both short- and long-term adverse outcomes in patients at cardiovascular risk undergoing major noncardiac surgery. Although prospective nonrandomised and retrospective data suggest heart rate control improves perioperative outcome, there is conflicting evidence from randomised trials that perioperative heart rate control improves outcome. This may be because drug-associated bradycardia influences mortality in the perioperative period. Further studies reporting the absolute heart rate, the absolute change of heart rate and the time period of the observations are needed to identify 'early warning systems', which may allow earlier triage and improved outcome. Enthusiasm for this approach must be tempered by the appreciation that a J-shaped relationship probably exists between heart rate and morbidity, particularly following bradycardic therapy. Therefore, any bradycardic manipulation of heart rate in the perioperative period must be accompanied by simultaneous attention to other physiological variables associated with increased morbidity and mortality.

  17. Effect of statins on survival in patients undergoing dialysis access for end-stage renal disease.

    PubMed

    De Rango, Paola; Parente, Basso; Farchioni, Luca; Cieri, Enrico; Fiorucci, Beatrice; Pelliccia, Selena; Manzone, Alessandra; Simonte, Gioele; Lenti, Massimo

    2016-12-01

    The benefit of statin therapy in patients with advanced chronic kidney disease remains uncertain. Randomized trials have questioned the efficacy of the drug in improving outcomes for on-dialysis populations, and many patients with end-stage renal disease are not currently taking statins. This study aimed to investigate the impact of statin use on survival of patients with vascular access performed at a vascular center for chronic dialysis. Consecutive end-stage renal disease patients admitted for vascular access surgery in 2006 to 2013 were reviewed. Information on therapy was retrieved and patients on statins were compared to those who were not on statins. Primary endpoint was 5-year survival. Independent predictors of mortality were assessed with Cox regression analysis adjusting for covariates (ie, age, sex, hyperlipidemia, hypertension, cardiac disease, cerebrovascular disease, chronic obstructive pulmonary disease, obesity, diabetes, and statins). Three hundred fifty-nine patients (230 males; mean age 68.9 ± 13.7 years) receiving 554 vascular accesses were analyzed: 127 (35.4%) were on statins. Use of statins was more frequent in patients with hypertension (89.8% v 81%; P = .034), hyperlipidemia (52.4% v 6.2%; P < .0001), coronary disease (54.1% v 42.6%; P = .043), diabetes (39.4% v 21.6%; P = .001), and obesity (11.6% v 2.0%; P < .0001). Mean follow-up was 35 months. Kaplan-Meier survival rates at 3 and 5 years were 84.4% and 75.9% for patients taking statins and 77.0% and 65.1% for those not taking statins (P = .18). Cox regression analysis selected statins therapy as the only independent negative predictor (odds ratio = 0.55; 95% confidence interval = 0.32-0.95; P = .032) of mortality, while age was an independent positive predictor (odds ratio = 1.05; 95% confidence interval = 1.03-1.08; P < .0001). Vascular access patency was comparable in statin takers and those not taking statins (P = .60). Use of statins might halve the risk of all-cause mortality at

  18. Prediction of presence of kidney disease in patients undergoing intravenous iodinated contrast enhanced computed tomography: a validation study.

    PubMed

    Schreuder, Sanne M; Stoker, Jaap; Bipat, Shandra

    2017-04-01

    To validate two previously presented models containing risk factors to identify patients with estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2) or eGFR <45 ml/min/1.73 m(2). In random patients undergoing intravenous contrast-enhanced computed tomography (CECT) the following risk factors were assessed: history of urological/nephrological disease, hypertension, diabetes mellitus, anaemia, congestive heart failure, other cardiovascular disease or multiple myeloma or Waldenström disease. Data on kidney function, age, gender and type and indication of CECT were also registered. We studied two models: model A-diabetes mellitus, history of urological/nephrological disease, cardiovascular disease, hypertension; model B-diabetes mellitus, history of urological/nephrological disease, age >75 years and congestive heart failure. For each model, associations with eGFR <60 ml/min/1.73 m(2) or eGFR <45 ml/min/1.73 m(2) was studied. A total of 1,001 patients, mean age 60.36 years were included. In total, 92 (9.2 %) patients had an eGFR <60 ml/min/1.73 m(2) and 11 (1.1 %) patients an eGFR <45 ml/min/1.73 m(2). Model A detected 543 patients: 81 with eGFR <60 ml/min/1.73 m(2) (missing 11) and all 11 with eGFR <45 ml/min/1.73 m(2). Model B detected 420 patients: 70 (missing 22) with eGFR <60 ml/min/1.73 m(2) and all 11 with eGFR <45 ml/min/1.73 m(2). Associations were significant (p < 0.05). Model B resulted in the lowest superfluous eGFR measurements while detecting all patients with eGFR <45 ml/min/1.73 m(2) and nearly all with eGFR <60 ml/min/1.73 m(2). • Less than 10% of patients undergoing contrast-enhanced CT have an eGFR of <60ml/min/1.73m (2) • Four risk factors can be used to detect pre-existent kidney disease • It is safe to reduce eGFR measurements using a four-risk-factor model.

  19. Pregnancy and cardiovascular risk: A review focused on women with heart disease undergoing fertility treatment.

    PubMed

    Rossberg, Nora; Stangl, Karl; Stangl, Verena

    2016-10-17

    A growing number of women with heart disease are considering pregnancy with the help of assisted reproductive technology (ART). Although an ever-increasing amount of knowledge exists on pregnancy in both congenital and acquired heart disease patients, little information is available on fertility treatments specifically in these women. This review seeks to provide an overview of the existing data and explores areas in need of research in this field. Changes in the hormonal environment seen in ART patients initially entail an increase then a decrease in blood pressure and peripheral vascular resistance. A shift in the thrombotic-thrombolytic balance towards coagulation is observed. Compared to normal pregnancy, ART-conceived pregnancies exhibit an increased adverse event rate for both the mother and foetus, including a higher incidence of hypertensive disorders and an increase in thromboembolic events during the first trimester. Ovarian hyperstimulation syndrome in particular can cause dramatic haemodynamic changes and an increase in upper body thrombosis. Viewing these findings within the context of women with an underlying heart disease reveals indications that maternal and neonatal complications after fertility treatments are higher. Pre-pregnancy risk assessment is essential to identifying women with heart disease for whom ART may be dangerous and therefore inappropriate.

  20. 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

  1. Oxygen pre-breathing decreases dysbaric diseases in UW sheep undergoing hyperbaric exposure.

    PubMed

    Sobakin, A S; Wilson, M A; Lehner, C E; Dueland, R T; Gendron-Fitzpatrick, A P

    2008-01-01

    Prolonged exposure of humans and animals to increased pressure as in a disabled submarine (DISSUB) can saturate the body's tissues with dissolved N2 as compressed air is breathed. Decompression-induced bubble formation in the long bone marrow cavity may lead to a bone compartment syndrome resulting in bone ischemia and necrosis. We tested oxygen pre-breathing prior to decompression in sheep to assess the effect upon dysbaric osteonecrosis (DON) induction in a DISSUB simulation experiment. A total of sixteen adult female sheep were used throughout the experiment. Four sheep were used as controls without oxygen pre-breathing. All sheep (99 +/- 14 kg SD) underwent dry chamber air exposure at 60 fsw (2.79 atm abs) (.2827 MPa) for 24 h followed by oxygen (88-92%) pre-breathing (15-min, 1-h, and 2-h and air for control) before "dropout" decompression at 30 fsw/min (0.91 atm/min). 99mTc-methylene diphosphonate (MDP) bone scans of the distal (radii and tibiae) long bones were used to detect "hot spots" of remodeling suggestive of DON lesions. Alizarin complexone fluorochrome was injected to visualize sites of metabolic activity indicating DON repair of both the proximal and distal long bones (radii, tibiae, femora, and humeri). Our findings showed that the amount of alizarin complexone deposition and bone scan uptake was greater in sheep with shorter oxygen pre-breathing times than those undergoing longer pre-breathing dives (p = 0.0056 and p = 0.001, for one and two hour pre-breathes respectively). Proximal limb bones (femur, humerus) displayed less alizarin complexone deposition than the distal radius and tibia (p < 0.0001).

  2. Effect of end-stage renal disease on oral health in patients undergoing renal dialysis: A cross-sectional study.

    PubMed

    Gautam, Nalam Radhika; Gautam, Nalam Sai; Rao, Thota Hanumantha; Koganti, Ravichandra; Agarwal, Rohit; Alamanda, Madhavi

    2014-09-01

    To evaluate the effect of chronic renal failure on oral health in renal dialysis patients. To assess and improvise awareness of staff regarding oral health care of the patients in hemodialysis unit. A cross-sectional questionnaire survey and oral health examination study were conducted on 206 end-stage chronic renal failure patients (stage V) who were undergoing renal dialysis in Guntur city. The study included the questionnaire form and modified WHO proforma to record their oral health status. Oral examination was done in American Dental Association (ADA) type III method by using mouth mirror and community periodontal index (CPI) probe. Questionnaire survey was conducted among the nursing staff in the hemodialysis unit. Mean age of the study subjects was 46.79 ± 12.78 years; 81.1% were males and 18.9% were females. Candidiasis (8.3%) was the most frequently seen oral mucosal condition in these subjects. Majority of the subjects (44.2%) showed periodontal diseases (CPI score 3: Pocket depth of 4-5 mm). Caries prevalence of 56.3% was seen in this study group. Higher incidence of hepatitis C was significantly associated with higher duration of dialysis. There was very little awareness among the nursing staff regarding dental care. There is greater deterioration of periodontal health among dialysis patients with chronic renal disease. Awareness regarding dental care is very less among patients undergoing renal dialysis. These patients should be monitored carefully to maintain their oral health. Awareness must be increased among dialysis patients and nursing staff about the need for primary prevention of dental diseases.

  3. Effects of silymarin on biochemical and oxidative stress markers in end-stage renal disease patients undergoing peritoneal dialysis.

    PubMed

    Firuzi, Omidreza; Khajehrezaei, Soraya; Ezzatzadegan, Shahrokh; Nejati, Maryam; Jahanshahi, Keramat-Allah; Roozbeh, Jamshid

    2016-10-01

    Introduction End-stage renal disease (ESRD) patients especially those undergoing dialysis are vulnerable to several complications, in particular those related to oxidative stress. Silymarin is an herbal medicine commonly used as an antioxidant in different pathologies. Methods To evaluate the effect of silymarin on biochemical and oxidative stress markers, 50 ESRD patients undergoing peritoneal dialysis were randomly divided into two groups of silymarin (n = 28) and control (n = 22) and received silymarin (140 mg every 8 hours) or placebo for 2 months, respectively. Ferric reducing antioxidant power and total 8-iso-prostaglandin F2α were measured in plasma, while catalase enzyme activity was measured in erythrocytes of both groups before and after treatment. Findings Ferric reducing antioxidant power values after treatment were significantly decreased in silymarin group compared to before treatment values (17.2 ± 2.9 and 15.9 ± 3.1 µM equivalent of quercetin/dL, respectively, P < 0.05). Conversely, catalase levels were increased 17.3% after silymarin consumption, while it was decreased 9.1% in control group. Further, hemoglobin (from 10.94 ± 2.17 to 11.54 ± 2.03 g/dL, P < 0.05) and albumin levels (from 3.48 ± 0.67 to 3.61 ± 0.53 g/dL, P < 0.05) were significantly increased after silymarin administration. Discussion It is concluded that silymarin could be regarded as a supplementary therapy for ESRD patients undergoing peritoneal dialysis in order to reduce complications. © 2016 International Society for Hemodialysis.

  4. Exercise testing in late-onset glycogen storage disease type II patients undergoing enzyme replacement therapy.

    PubMed

    Marzorati, Mauro; Porcelli, Simone; Bellistri, Giuseppe; Morandi, Lucia; Grassi, Bruno

    2012-12-01

    Enzyme replacement therapy (ERT) has recently became available for patients with glycogen storage disease type II. Previous studies have demonstrated clinical efficacy of enzyme replacement therapy, however, data on physiological variables related to exercise tolerance are scarce. Four glycogen storage disease type II late-onset patients (45 ± 6 years) performed an incremental exercise on a cycle ergometer, up to voluntary exhaustion, before (BEFORE) and after 12 months of ERT (AFTER). Peak workload, oxygen uptake, heart rate, cardiac output (by impedance cardiography) and vastus lateralis oxygenation indices (by continuous-wave near-infrared spectroscopy, NIRS) were determined. Peak workload and oxygen uptake values significantly increased during ERT (54 ± 30 vs. 63 ± 31 watt, and 17.2 ± 4.4 vs. 19.7 ± 3.5 ml/kg/min, respectively, in BEFORE vs. AFTER). On the other hand, for both peak cardiac output (12.3 ± 5.3 vs. 14.8 ± 4.5L/min) and the NIRS-determined peak skeletal muscle fractional O(2) extraction, expressed as a percentage of the maximal values during a transient limb ischemia (30 ± 39% vs. 38 ± 28%), the observed increases were not statistically significant. Our findings suggest that in glycogen storage disease type II patients enzyme replacement therapy is associated with a mild improvement of exercise tolerance. The findings need to be validated during a longer follow-up on a larger group of patients.

  5. A multigene array for measurable residual disease detection in AML patients undergoing SCT

    PubMed Central

    Goswami, M; McGowan, K S; Lu, K; Jain, N; Candia, J; Hensel, N F; Tang, J; Calvo, K R; Battiwalla, M; Barrett, A J; Hourigan, C S

    2015-01-01

    AML is a diagnosis encompassing a diverse group of myeloid malignancies. Heterogeneous genetic etiology, together with the potential for oligoclonality within the individual patient, have made the identification of a single high-sensitivity marker of disease burden challenging. We developed a multiple gene measurable residual disease (MG-MRD) RQ–PCR array for the high-sensitivity detection of AML, retrospectively tested on 74 patients who underwent allo-SCT at the NHLBI in the period 1994–2012. MG-MRD testing on peripheral blood samples prior to transplantation demonstrated excellent concordance with traditional BM-based evaluation and improved risk stratification for post-transplant relapse and OS outcomes. Pre-SCT assessment by MG-MRD predicted all clinical relapses occurring in the first 100 days after allo-SCT compared with 57% sensitivity using WT1 RQ–PCR alone. Nine patients who were negative for WT1 prior to transplantation were correctly reclassified into a high-risk MG-MRD-positive group, associated with 100% post-transplant mortality. This study provides proof of principle that a multiple gene approach may be superior to the use of WT1 expression alone for AML residual disease detection. PMID:25665046

  6. The Importance of Patency in Patients with Critical Limb Ischemia Undergoing Endovascular Revascularization for Infrapopliteal Arterial Disease

    PubMed Central

    Baumann, Frederic; Ozdoba, Christoph; Gröchenig, Ernst; Diehm, Nicolas

    2015-01-01

    Critical limb ischemia (CLI) represents the most severe form of peripheral arterial disease (PAD) and frequently occurs in medically frail patients. CLI patients frequently exhibit multi-segmental PAD commonly including the tibial arterial segment. Endovascular therapy has been established as first-line revascularization strategy for most CLI patients. Restenosis was reported to occur in up to more than two-thirds of CLI patients undergoing angioplasty of complex tibial arterial obstructions. Nevertheless, favorable clinical outcomes were observed for infrapopliteal angioplasty when compared with bypass surgery, despite higher patency rates for the latter. Based on these observations, infrapopliteal patency was considered to be only of secondary importance upon clinical outcomes in CLI patients. In contrast to these earlier observations, however, recent findings from two randomized clinical trials indicate that infrapopliteal patency does impact on clinical outcomes in CLI patients. The purpose of the present manuscript is to provide a critical reappraisal of the present literature on the clinical importance of tibial arterial patency in CLI patients undergoing endovascular revascularization and to discuss utility and limitations of currently available anti-restenosis technologies. PMID:26664867

  7. Prevalence and risk factors for pulmonary arterial hypertension in end-stage renal disease patients undergoing continuous ambulatory peritoneal dialysis.

    PubMed

    Zhang, Lei; Zhao, Shiqi; Ma, Jinling; Gong, Jian; Qiu, Guizhen; Ren, Yueqin; Zen, Ying; Shi, Yongbing

    2016-06-01

    Pulmonary arterial hypertension (PAH) is a major complication in renal failure patients, but very little information is available on the cardiovascular parameters in these patients. The prevalence and risk factors for PAH were systematically evaluated in patients with end-stage renal diseases (ESRD) undergoing continuous ambulatory peritoneal dialysis (CAPD). Between January 2010 and January 2014, 177 ESRD patients (85 males and 92 females) undergoing CAPD therapy were recruited. General data, biochemical parameters and echocardiographic findings were collected and PAH risk factors studied. Study participants consisted of 65 patients (36.52%) with PAH (PAH group) and 112 patients without PAH (non-PAH group). The interdialytic weight gain, systolic blood pressure and diastolic blood pressure (DBP), mean arterial pressure and hypertensive nephropathy incidence in the PAH group were significantly higher than the non-PAH group (all p < 0.05). There were significant differences between PAH group and non-PAH group in C-reactive protein-positive rate, N-terminal pro-brain natriuretic peptide (NT-proBNP), hemoglobin, prealbumin and serum albumin levels (all p < 0.05). Compared with non-PAH group, PAH group showed significant increases in right ventricular internal diameter (RVID), right ventricular outflow tract diameter (RVOTD), main pulmonary artery diameter, left atrial diameter (LAD), left ventricular end-diastolic diameter, interventricular septal thickness, left ventricular mass index, early diastolic mitral annulus velocity and valve calcification incidence (all p < 0.05), and decreased left ventricular ejection fraction (LVEF), tricuspid annulus plane systolic excursion (TAPSE) and early diastolic blood flow peak and mitral annulus velocity (E/E') (all p < 0.05). Logistic regression analysis revealed that DBP, NT-proBNP, LAD, RVID, RVOTD, LVEF, TAPSE and E/E' are major risk factors for PAH. We observed a high incidence of PAH in ESRD patients

  8. Exercise testing in late-onset glycogen storage disease type II patients undergoing enzyme replacement therapy

    PubMed Central

    Marzorati, Mauro; Porcelli, Simone; Bellistri, Giuseppe; Morandi, Lucia; Grassi, Bruno

    2012-01-01

    Enzyme replacement therapy (ERT) has recently became available for patients with glycogen storage disease type II. Previous studies have demonstrated clinical efficacy of enzyme replacement therapy, however, data on physiological variables related to exercise tolerance are scarce. Four glycogen storage disease type II late-onset patients (45 ± 6 years) performed an incremental exercise on a cycle ergometer, up to voluntary exhaustion, before (BEFORE) and after 12 months of ERT (AFTER). Peak workload, oxygen uptake, heart rate, cardiac output (by impedance cardiography) and vastus lateralis oxygenation indices (by continuous-wave near-infrared spectroscopy, NIRS) were determined. Peak workload and oxygen uptake values significantly increased during ERT (54 ± 30 vs. 63 ± 31 watt, and 17.2 ± 4.4 vs. 19.7 ± 3.5 ml/kg/min, respectively, in BEFORE vs. AFTER). On the other hand, for both peak cardiac output (12.3 ± 5.3 vs. 14.8 ± 4.5 L/min) and the NIRS-determined peak skeletal muscle fractional O2 extraction, expressed as a percentage of the maximal values during a transient limb ischemia (30 ± 39% vs. 38 ± 28%), the observed increases were not statistically significant. Our findings suggest that in glycogen storage disease type II patients enzyme replacement therapy is associated with a mild improvement of exercise tolerance. The findings need to be validated during a longer follow-up on a larger group of patients. PMID:23182645

  9. Risk of thromboembolic disease in men with prostate cancer undergoing androgen deprivation therapy.

    PubMed

    O'Farrell, Sean; Sandström, Karin; Garmo, Hans; Stattin, Pär; Holmberg, Lars; Adolfsson, Jan; Van Hemelrijck, Mieke

    2016-09-01

    To investigate the risk of thromboembolic disease (TED) in men with prostate cancer (PCa) on androgen deprivation therapy (ADT), while accounting for known TED risk factors. We assessed TED risk for 42 263 men with PCa who were receiving ADT compared with a matched cohort of 190 930 without PCa. The associations between ADT and deep vein thrombosis (DVT) or pulmonary embolism (PE) were analysed using multivariate Cox proportional hazard regression models, while accounting for previous PCa-related surgeries and the following proxies for disease progression: transurethral resection of the prostate, palliative radiotherapy and nephrostomy. Between 1997 and 2013, 11 242 men with PCa received anti-androgen monotherapy, 26 959 men received gonadotropin-releasing hormone (GnRH) agonists, 1 091 men received combined androgen blockade and 3 789 men underwent orchiectomy. When accounting for previous surgeries and proxies of disease progression, GnRH agonist users and surgically castrated men had a higher risk of TED than the comparison cohort: hazard ratios (HRs) 1.67 (95% confidence interval [CI] 1.40-1.98) and 1.61 (95% CI 1.15-2.28), respectively. Men on anti-androgen monotherapy had a lower risk: HR for DVT 0.49 (95% CI 0.33-0.74). TED risk was highest among those who switched from anti-androgen to GnRH agonists: HR for PE 2.55 (95% CI 1.76-3.70). This increased from 2.52 (95% CI 1.54-4.12) in year 1, to 4.05 (95% CI 2.51-6.55) in year 2. The incidence of TED among men on ADT increased with the duration of therapy and the risk was highest for those who switched regimen, suggesting that disease progression as well as ADT contribute to the propagation of TED risk. Nonetheless, these findings support the hypothesis that only men with a relevant indication should receive systemic ADT. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

  10. Nutritional status in Parkinson's disease patients undergoing deep brain stimulation surgery: a pilot study.

    PubMed

    Sheard, J M; Ash, S; Silburn, P A; Kerr, G K

    2013-02-01

    People with Parkinson's disease (PD) are at higher risk of malnutrition due to PD symptoms and pharmacotherapy side effects. When pharmacotherapy is no longer effective for symptom control, deep-brain stimulation (DBS) surgery may be considered. The aim of this study was to assess the nutritional status of people with PD who may be at higher risk of malnutrition related to unsatisfactory symptom management with optimised medical therapy. This was an observational study using a convenience sample. Participants were seen during their hospital admission for their deep brain stimulation surgery. People with PD scheduled for DBS surgery were recruited from a Brisbane neurological clinic (n=15). The Patient-Generated Subjective Global Assessment (PG-SGA), weight, height and body composition were assessed to determine nutritional status. Six participants (40%) were classified as moderately malnourished (SGA-B). Eight participants (53%) reported previous unintentional weight loss (average loss of 13%). On average, participants classified as well-nourished (SGA-A) were younger, had shorter disease durations, lower PG-SGA scores, higher body mass (BMI) and fat free mass indices (FFMI) when compared to malnourished participants (SGA-B). Five participants had previously received dietetic advice but only one in relation to unintentional weight loss. Malnutrition remains unrecognised and untreated in this group despite unintentional weight loss and presence of nutrition impact symptoms. Improving nutritional status prior to surgery may improve surgical outcomes.

  11. Neurocognitive Improvement in Patients Undergoing Carotid Endarterectomy for Atherosclerotic Occlusive Carotid Artery Disease

    PubMed Central

    Jamil, Muhammad; Haq, Imran Ul; Memon, Amir Ali

    2016-01-01

    Objectives: To assess the improvement in neurocognitive functions after carotid endarterectomy (CEA) under local anesthesia (LA) in patients with carotid bifurcation occlusive disease. Place and duration of study: Department of Vascular Surgery, Combined Military Hospital Lahore from January 2013 to January 2015. Patients and Methods: A total of 79 patients with carotid artery occlusive disease, having no history of major stroke, depression, or dementia underwent CEA under LA. Cognitive functions were assessed 3 days before surgery and then 4 weeks and 12 weeks after the surgery using the Addenbrookes cognitive examination (ACE) score and General Practitioner Assessment of Cognition (GPCOG) Score. Results: In ACE score, Attention, Memory, Fluency, Language, and Visuospatial orientation improved by 33.3%, 30.7%, 21.4%, 38.4%, and 31.2%, respectively, by the end of 12 weeks. An overall improvement in neurocognition was 32% (P = 0.03). In GPCOG score, Orientation, Recall, and Memory improved by 33%, 20%, and 100%, respectively, with an overall improvement of 33.3% at the end of 12 weeks (P = 0.02). Conclusion: Both scoring systems show an overall improvement in neurocognition as well as improvements in all the subcategories in each system. Hence, we conclude statistically significant improvement in neurocognitive functions after CEA. PMID:28018503

  12. The frequency of anesthesia-related cardiac arrests in patients with congenital heart disease undergoing cardiac surgery.

    PubMed

    Odegard, Kirsten C; DiNardo, James A; Kussman, Barry D; Shukla, Avinash; Harrington, James; Casta, Al; McGowan, Francis X; Hickey, Paul R; Bacha, Emile A; Thiagarajan, Ravi R; Laussen, Peter C

    2007-08-01

    The frequency of anesthesia-related cardiac arrests during pediatric anesthesia has been reported between 1.4 and 4.6 per 10,000 anesthetics. ASA physical status >III and younger age are risk factors. Patients with congenital cardiac disease may also be at increased risk. Therefore, in this study, we evaluated the frequency of cardiac arrest in patients with congenital heart disease undergoing cardiac surgery at a large pediatric tertiary referral center. Using an established data registry, all cardiac arrests from January 2000 through December 2005 occurring in the cardiac operating rooms were reviewed. A cardiac arrest was defined as any event requiring external or internal chest compressions, with or without direct cardioversion. Events determined to be anesthesia-related were classified as likely related or possibly related. There were 41 cardiac arrests in 40 patients (median age, 2.9 mo; range, 2 days to 23 yr) during 5213 anesthetics over the time period, for an overall frequency of 0.79%; 78% were open procedures requiring cardiopulmonary bypass and 22% closed procedures not requiring cardiopulmonary bypass. Eleven cardiac arrests (26.8%) were classified as either likely (n = 6) or possibly related (n = 5) to anesthesia, (21.1 per 10,000 anesthetics) but with no mortality; 30 were categorized as procedure-related. The incidence of anesthesia-related and procedure-related cardiac arrests was highest in neonates (P < 0.001). There was no association with year of event or experience of the anesthesiologist. The frequency of anesthesia-related cardiac arrest in patients undergoing cardiac surgery is increased, but is not associated with an increase in mortality. Neonates and infants are at higher risk. Careful preparation and anticipation is important to ensure timely and effective resuscitation.

  13. Circulating TNF Receptors 1 and 2 Predict Mortality in Patients with End-stage Renal Disease Undergoing Dialysis

    PubMed Central

    Gohda, Tomohito; Maruyama, Shuntaro; Kamei, Nozomu; Yamaguchi, Saori; Shibata, Terumi; Murakoshi, Maki; Horikoshi, Satoshi; Tomino, Yasuhiko; Ohsawa, Isao; Gotoh, Hiromichi; Nojiri, Shuko; Suzuki, Yusuke

    2017-01-01

    Relatively high circulating levels of soluble tumor necrosis factor (TNF) receptors (TNFRs: TNFR1, TNFR2) have been associated with not only progression to end-stage renal disease but also mortality in patients with diabetes. It remains unknown whether elevated TNFR levels in haemodialysis patients are associated with mortality. We studied 319 patients receiving maintenance haemodialysis who were followed for a median of 53 months. Circulating markers of TNF pathway (TNFα and TNFRs) were measured with immunoassay. Strong positive correlations between TNFR1 and TNFR2 were observed (r = 0.81, P < 0.0001). During follow-up, 88 (27.6%) patients died of any cause (40 [45.5%] died of cardiovascular disease). In the Cox multivariate model, either TNFR but not TNFα remained a significant independent predictor of all-cause mortality (TNFR1: hazard ratio [HR] 2.34, 95% confidence interval [CI], 1.50–3.64; TNFR2: HR 2.13, 95% CI 1.38–3.29) after adjustment for age, prior cardiovascular disease, predialysis systolic blood pressure, and large systolic blood pressure decline during dialysis session. For cardiovascular mortality, significance was only observed in TNFR1 (TNFR1: HR 2.15, 95% CI 1.13–4.10). Elevated TNFRs levels were associated with the risk of cardiovascular and/or all-cause mortality independent of all relevant covariates in patients undergoing haemodialysis. PMID:28256549

  14. Risk Factors for Suboptimal Utilization of Statins and Antiplatelet Therapy in Patients Undergoing Revascularization for Symptomatic Peripheral Arterial Disease.

    PubMed

    Meltzer, Andrew J; Sedrakyan, Art; Connolly, Peter H; Ellozy, Sharif; Schneider, Darren B

    2017-06-08

    The objective of this study was to identify risk factors for suboptimal medical therapy (defined as reported antiplatelet and statin use) among patients undergoing lower extremity bypass (LEB) and peripheral vascular interventions (PVIs) for symptomatic peripheral arterial disease (PAD). The Vascular Study Group of Greater New York (VSGGNY) database was used to identify all patients undergoing PVI or LEB for PAD (2011-2013). Bivariate analyses were performed to identify characteristics of patients who were not prescribed statins and/or antiplatelet agents before revascularization. Multivariate relative risk regression models were developed to identify patients at risk for suboptimal therapy, with regards to antiplatelet and statin therapy. About 1,030 patients underwent endovascular therapy (n = 822; 80%) or surgical bypass (n = 208; 20%) for symptomatic PAD (57.2% claudication; 15% rest pain and 27.8% tissue loss). Overall, preoperative statin use was observed in 59%. Preoperative antiplatelet therapy was observed in 79% of patients. Bivariate analysis revealed comparatively reduced statin use among patients without other cardiovascular risk factors including hypertension (63% vs. 39.3%; P < 0.0001) and coronary artery disease (CAD) with or without prior cardiac revascularization (coronary artery bypass grafting [CABG]/percutaneous coronary intervention [PCI]; 75.2% vs. 47.4%; P < 0.0001). Multivariate relative risk regression confirmed higher rates of statin use among patients with other cardiovascular risk factors including hypertension (1.14 [1.02-1.27]; P = 0.02) and CAD with prior CABG/PCI (1.22 [1.13-1.31]; P < 0.0001). Reduced statin use was observed in patients over 80 years old. (0.92 [0.84-0.1.0]; P = 0.059). By multivariate regression, antiplatelet therapy use was associated with CAD and/or prior CABG/PCI (1.11 [1.04-1.17]; P = 0.0015) and prior peripheral revascularization (1.07 [1.01-1.13]; P = 0.03). Patients with symptomatic PAD

  15. Effect of nutritional status in individuals with chronic obstructive pulmonary disease undergoing pulmonary rehabilitation.

    PubMed

    Günay, Ersin; Kaymaz, Dicle; Selçuk, Nursel Türkoglu; Ergün, Pinar; Sengül, Fatma; Demir, Nese

    2013-11-01

    Chronic obstructive pulmonary disease (COPD) is considered a worldwide major public health problem. Weight loss, muscle and fat mass depletion are common nutritional problems in COPD patients and are determinant factors in pulmonary function, health status, disability and mortality. We aimed to assess the relationships between nutritional status and perception of dyspnoea, pulmonary function tests (PFT), exercise capacity and health-related quality of life (HRQoL) using the subjective global assessment (SGA) in COPD patients who were referred for pulmonary rehabilitation programme. A total of 163 patients with stable COPD who are candidates for outpatient pulmonary rehabilitation programme were included in this study. Nutritional status for all patients was assessed by SGA. Association of SGA scores (A, B and C) and anthropometric measurements, PFT, dyspnoea scales (Medical Research Council and resting BORG scale), HRQoL (St. George Respiratory Questionnaire and Chronic Respiratory Diseases Questionnaire) and exercise testing (shuttle walking test) were studied for statistical significance. Based on SGA, 9.2% of patients were severely malnourished (SGA-C). There were significant decreases in forced expiratory volume in the first second (FEV1 ) (P = 0.009), Medical Research Council scales (P < 0.001) and exercise capacity (incremental shuttle walking test (P = 0.001) and endurance shuttle walking test (P = 0.009)) in SGA-C. Deterioration in anthropometric measurements and HRQoL measures were observed in malnourished patients. Identifying the nutritional status and determining any requirement for nutritional supplement is an important component of comprehensive pulmonary rehabilitation programme. SGA is an easy and practical method to assess nutritional status in pulmonary rehabilitation candidate patients with stable COPD. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

  16. Permanent cardiac pacing in patients with end-stage renal disease undergoing dialysis.

    PubMed

    Wang, I-Kuan; Lin, Kuo-Hung; Lin, Shih-Yi; Lin, Cheng-Li; Chang, Chiz-Tzung; Yen, Tzung-Hai; Sung, Fung-Chang

    2016-12-01

    Studies investigating the risk of cardiac dysrhythmia warranting permanent pacemaker therapy for end-stage renal disease (ESRD) patients are limited. This study investigated the incidence rate of permanent cardiac pacing in dialysis patients. Using the Taiwan National Health Insurance Database, we identified 28 471 newly diagnosed ESRD patients in 2000-2010 [9700 on peritoneal dialysis (PD) and 18 771 on hemodialysis (HD)] and 113 769 randomly selected controls without kidney disease, frequency-matched by sex, age and diagnosis date. We also established propensity score-matched HD and PD cohorts with 9700 patients each. Incidence rates and hazard ratios (HRs) of implantation were evaluated by the end of 2011. Complications were also evaluated among patients with implantation. The incidence rates of permanent pacemaker implantation were 5.93- and 3.50-fold greater in HD and PD patients than in controls (1.44 and 0.85 versus 0.24 per 1000 person-years, respectively). The adjusted HRs (aHRs) of implantation were 3.26 [95% confidence interval (CI) = 2.41-4.42] and 2.36 (95% CI = 1.56-3.58) for HD and PD patients, respectively, compared with controls. The pacemaker implantation rate was 0.33 per 1000 person-years greater in the propensity score-matched HD cohort than in the PD cohort, with an aHR of 1.30 (95% CI = 0.82-2.05) for the HD cohort compared with the PD cohort. Dialysis patients are at an increased risk of dysrhythmia requiring pacemaker implantation compared with the general population. The risks are not significantly different between HD and PD patients. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  17. 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

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

    PubMed

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

    2010-08-01

    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. 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. 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%. 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.

  19. Postoperative Outcomes in Vedolizumab-Treated Patients Undergoing Abdominal Operations for Inflammatory Bowel Disease.

    PubMed

    Lightner, Amy L; Raffals, Laura E; Mathis, Kellie L; Cima, Robert R; Tse, Chung Sang; Pemberton, John H; Dozois, Eric J; Loftus, Edward V

    2017-02-01

    Vedolizumab was recently approved by the Food and Drug Administration for the treatment of moderate to severe ulcerative colitis [UC] and Crohn's disease [CD]. No study to date has examined the rate of postoperative infectious complications among patients who received vedolizumab in the perioperative period. We sought to determine the 30-day postoperative infectious complication rate among inflammatory bowel disease [IBD] patients who received vedolizumab within 12 weeks of an abdominal operation as compared to patients who received tumour necrosis factor α [TNFα] inhibitors or no biological therapy. A retrospective chart review between May 1, 2014 and December 31, 2015 of adult IBD patients who underwent an abdominal operation was performed. The study cohort comprised patients who received vedolizumab within 12 weeks of their abdominal operation and the control cohorts were patients who received TNFα inhibitors or no biological therapy. In total, 94 patients received vedolizumab within 12 weeks of an abdominal operation. Fifty experienced postoperative complications [53%], 35 of which were surgical site infections [SSIs] [36%]. The vedolizumab group experienced significantly higher rates of any postoperative infection [53% vs 33% anti-TNF and 28% non-biologics; p<0.001] and SSI [37% vs 10% and 13%; p<0.001]. On univariate and multivariate analysis, exposure to vedolizumab remained a significant predictor of postoperative SSI [p<0.001]. Thirty-seven per cent of IBD patients who received vedolizumab within 30 days of a major abdominal operation experienced a 30-day postoperative SSI, significantly higher than patients receiving TNFα inhibitors or no biological therapy. Vedolizumab within 12 weeks of surgery remained the only predictor of 30-day postoperative SSI on multivariate analysis. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  20. Pseudo-outbreak of legionnaires disease among patients undergoing bronchoscopy - Arizona, 2008.

    PubMed

    2009-08-14

    Legionnaires disease (LD) is a potentially fatal form of pneumonia acquired by inhalation of aerosolized water containing Legionella bacteria. Legionella is a common cause of health-care--associated pneumonia, particularly in settings with hematopoietic stem-cell or solid-organ transplant recipients. On July 25, 2008, the Arizona Department of Health Services (ADHS) notified CDC of four patients who had Legionella cultured from specimens obtained during bronchoscopies performed at a medical center in Arizona. To characterize transmission and identify the source, ADHS and CDC began an investigation on August 1. This report summarizes the results of that investigation, which determined that the patients did not have LD and that nonsterile ice used to cool saline-filled syringes for bronchoalveolar lavage was the likely source of Legionella contamination of these clinical specimens. Ice was supplied by two ice machines, which became contaminated by heavy Legionella colonization within the center's potable water supply during a 6-month period (February--July 2008). Findings from the investigation underscore the importance of adherence to recommended infection control practices and surveillance for LD in health-care settings. Clinicians and endoscopy technicians should ensure that nonsterile items are not introduced during bronchoscopy procedures.

  1. Pharmacokinetics, safety, and tolerability of edoxaban in end-stage renal disease subjects undergoing haemodialysis.

    PubMed

    Parasrampuria, Dolly A; Marbury, Thomas; Matsushima, Nobujo; Chen, Shuquan; Wickremasingha, Prachi K; He, Ling; Dishy, Victor; Brown, Karen S

    2015-04-01

    Edoxaban is an oral, direct, once-daily, factor Xa inhibitor developed for stroke prevention in patients with atrial fibrillation and for the treatment and secondary prevention of recurrent thromboembolism in patients with acute symptomatic venous thromboembolism. Among elderly patients who require anticoagulation therapies, some may have end-stage renal disease (ESRD). This open-label, phase 1, randomised, two-way crossover study was conducted to evaluate the pharmacokinetics of edoxaban in 10 subjects on haemodialysis. Eligible subjects with ESRD on chronic haemodialysis received a single, oral dose of edoxaban 15 mg 2 hours (h) prior to (on-dialysis) or in between (off-dialysis) haemodialysis sessions. Haemodialysis resulted in a minor decrease in mean total exposure (AUC0-∞; 676.2 ng·h/ml) as compared with that observed in subjects off-dialysis (691.7 ng·h/ml). Mean maximum observed plasma concentration (Cmax) values were comparable between on-dialysis and off-dialysis treatments (53.3 vs 56.3 ng/ml, respectively). Mean apparent total body clearance (CL/F) values were 24.1 and 22.5 l/h during the on-dialysis and off-dialysis treatment periods, respectively. Dialyser clearance was 5.7 l/h and haemodialysis clearance was 6.1 l/h. Haemodialysis clearance was only 6.1 l/h, suggesting that it only accounts for one-fourth of the total clearance in these subjects. A single, oral dose of 15 mg of edoxaban was well tolerated by subjects with ESRD. In conclusion, based on these single-dose PK data, a supplementary dose of edoxaban may not be required following a haemodialysis session. Importantly, haemodialysis is not an effective mechanism for removal of edoxaban from the blood.

  2. Evidence that neurones accumulating amyloid can undergo lysis to form amyloid plaques in Alzheimer's disease.

    PubMed

    D'Andrea, M R; Nagele, R G; Wang, H Y; Peterson, P A; Lee, D H

    2001-02-01

    Amyloid has recently been shown to accumulate intracellularly in the brains of patients with Alzheimer's disease (AD), yet amyloid plaques are generally thought to arise from gradual extracellular amyloid deposition. We have investigated the possibility of a link between these two apparently conflicting observations. Immunohistochemistry and digital image analysis was used to examine the detailed localization of beta-amyloid(42) (A beta 42), a major component of amyloid plaques, in the entorhinal cortex and hippocampus of AD brains. A beta 42 first selectively accumulates in the perikaryon of pyramidal cells as discrete, granules that appear to be cathepsin D-positive, suggesting that they may represent lysosomes or lysosome-derived structures. AD brain regions abundantly populated with pyramidal neurones exhibiting excessive A beta 42 accumulations also contained evidence of neuronal lysis. Lysis of these A beta 42-burdened neurones apparently resulted in a local, radial dispersion of their cytoplasmic contents, including A beta 42 and lysosomal enzymes, into the surrounding extracellular space. A nuclear remnant was found at the dense core of many amyloid plaques, strengthening the idea that each amyloid plaque represents the end product of a single neuronal cell lysis. The inverse relationship between the amyloid plaque density and pyramidal cell density in the AD brain regions also supports this possibility, as does the close correlation between plaque size and the size of local pyramidal cells. Our findings suggest that excessive intracellular accumulation of A beta 42-positive material in pyramidal cells can result in cell lysis, and that cell lysis is an important source of amyloid plaques and neuronal loss in AD brains.

  3. [Frequency of postoperative fever in children with congenital heart disease undergoing cardiovascular surgery and associated risk factors].

    PubMed

    Villasís-Keever, Miguel A; Zapata-Arenas, Delia M; Penagos-Paniagua, Martín J

    2002-10-01

    To determine the frequency of postoperative fever in children with congenital heart disease who undergo cardiovascular surgery, and the risk factors associated. In a prospective cohort study, 100 children under the age of less than 9 years were followed-up during hospitalization in order to detect fever after cardiac surgery. Preoperative, perioperative, and postoperative variables were assessed to determine their relationship with postoperative fever. The cases were patients who developed fever. Multivariate analysis was used, and the odds ratio (OR) and 95% confidence intervals (95% CI) were calculated. The frequency of postoperative fever was 46%. Fever appeared within 24 hours of surgery in 56% cases. In 32/46 (70%) cases, fever remitted within 72 hours. Fever was more common in patients who underwent open-heart surgery than in those treated with a closed technique (28 vs. 18, P = 0.045). Prolonged extracorporeal circulation (OR = 1.024; 95% CI, 1.004-1.045), aortic cross-clamping (OR = 2.83; 95% CI, 1.21-6.61) and postoperative infections (OR = 24.07; 95% CI, 7.2-75.0) were the risk factors associated with the development of postoperative fever. Postoperative fever is common in children with congenital heart disease. The identification of risk factors associated to the development of fever should help clinicians to identify the cause of fever in this group of patients.

  4. Relation of routine, periodic fasting to risk of diabetes mellitus, and coronary artery disease in patients undergoing coronary angiography.

    PubMed

    Horne, Benjamin D; Muhlestein, Joseph B; May, Heidi T; Carlquist, John F; Lappé, Donald L; Bair, Tami L; Anderson, Jeffrey L

    2012-06-01

    Previously we discovered that routine periodic fasting was associated with a lower prevalence of coronary artery disease (CAD). Other studies have shown that fasting increases longevity in animals. A hypothesis-generating analysis suggested that fasting may also associate with diabetes. This study prospectively tested whether routine periodic fasting is associated with diabetes mellitus (DM). Patients (n = 200) undergoing coronary angiography were surveyed for routine fasting behavior before their procedure. DM diagnosis was based on physician reports of current and historical clinical and medication data. Secondary end points included CAD (physician reported for ≥ 1 lesion of ≥ 70% stenosis), glucose, and body mass index (BMI). Meta-analyses were performed by evaluation of these patients and 448 patients from a previous study. DM was present in 10.3% of patients who fasted routinely and 22.0% of those who do not fast (odds ratio [OR] 0.41, 95% confidence interval [CI] 0.17 to 0.99, p = 0.042). CAD was found in 63.2% of fasting and 75.0% of nonfasting patients (OR 0.42, CI 0.21 to 0.84, p = 0.014), and in nondiabetics this CAD association was similar (OR 0.38, CI 0.16 to 0.89, p = 0.025). Meta-analysis showed modest differences for fasters versus nonfasters in glucose concentrations (108 ± 36 vs 115 ± 46 mg/dl, p = 0.047) and BMI (27.9 ± 5.3 vs 29.0 ± 5.8 kg/m(2), p = 0.044). In conclusion, prospective hypothesis testing showed that routine periodic fasting was associated with a lower prevalence of DM in patients undergoing coronary angiography. A reported fasting association with a lower CAD risk was also validated and fasting associations with lower glucose and BMI were found. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Inhibition of inflammation mediates the protective effect of atorvastatin reload in patients with coronary artery disease undergoing noncardiac emergency surgery.

    PubMed

    Qu, Yang; Wei, Lixin; Zhang, Haiqing

    2014-12-01

    This study aimed to (a) investigate whether atorvastatin reload protects against acute heart failure (AHF) in patients with stable coronary artery disease (CAD) undergoing noncardiac emergency surgery and decreases the incidence of major adverse cardiac events (MACE) during hospitalization and (b) elucidate its possible mechanism of action. In total, 500 patients with stable CAD before noncardiac emergency surgery were randomized either to the atorvastatin reload or to the placebo group. All patients received atorvastatin treatment postoperatively. The primary end point was the incidence of AHF during hospitalization, and the secondary end point was the incidence of MACE during hospitalization. Preoperative and 72 h postoperative changes in high-sensitivity C-reactive protein and interleukin-6 levels were compared between the two groups. AHF during hospitalization occurred in 5.2% of patients in the atorvastatin reload group and 11.2% in the placebo group (P=0.0225). MACE during hospitalization occurred in 2.4% of patients in the atorvastatin reload group and 8.0% in the placebo group (P=0.0088). According to multivariable analysis, atorvastatin reload conferred a 50% reduction in the risk of AHF during hospitalization (odds ratio, 0.50; 95% confidence interval, 0.2-0.8; P=0.005). The median decrease in the high-sensitivity C-reactive protein and interleukin-6 levels was significantly greater in the atorvastatin reload group (P<0.001). Atorvastatin reload may improve the clinical outcome of patients with stable CAD undergoing noncardiac emergency surgery by decreasing the incidence of AHF and MACE during hospitalization. The mechanism of this protective effect may involve inhibition of inflammation.

  6. 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

  7. Clinical characteristics of rheumatoid arthritis patients undergoing cervical spine surgery: an analysis of National Database of Rheumatic Diseases in Japan.

    PubMed

    Sugita, Shurei; Chikuda, Hirotaka; Kadono, Yuho; Ohtsu, Hiroshi; Takeshita, Katsushi; Nishino, Jinju; Tohma, Shigeto; Tanaka, Sakae

    2014-06-13

    The aim of this study was to examine the clinical characteristics of rheumatoid arthritis (RA) patients who underwent cervical spine surgery using a multicenter observational database. We obtained data from a nationwide observational cohort database of patients with rheumatic diseases (National Database of Rheumatic Diseases by iR-net in Japan (NinJa)) for the fiscal years 2003 to 2011. A total of 39 out of 60 patients who underwent cervical spine surgery for a RA-related cause and whose data were available for two consecutive years (to assess the preoperative patient status) were chosen as cases. Patients with a non-RA-related cause of surgery (e.g., trauma) were excluded. First, we compared the patient characteristics between the cases and total patients in the same fiscal year. Next, 106 eligible controls, who were defined as RA patients enrolled in the same fiscal year as the case subjects, who were matched for age, gender and disease duration (within ±1 year), were selected. We compared the demographic data between the two groups. We also calculated the percentage of patients who underwent cervical spine surgery (surgeries/total number of patients) in fiscal years 2003 to 2011. Although the proportion of patients using biologics linearly increased during study period, the percentage of patients undergoing cervical spine surgeries remained unchanged, at approximately 0.15%. These cases had more tender joints (3 vs. 1, p < 0.01) and exhibited a significantly higher Modified Health Assessment Questionnaire (MHAQ) score (1.13 vs. 0.5, p < 0.01), C-reactive protein (CRP) (1.5 vs. 0.36, p < 0.01), and disease activity score (DAS) 28-CRP (3.63 vs. 2.81, p < 0.01) compared to the controls. Our study revealed that RA patients requiring cervical spine surgery have a higher disease activity (as represented by the DAS28-CRP) and are more functionally disabled (as represented by the MHAQ) than control patients.

  8. Clinical characteristics of rheumatoid arthritis patients undergoing cervical spine surgery: an analysis of National Database of Rheumatic Diseases in Japan

    PubMed Central

    2014-01-01

    Background The aim of this study was to examine the clinical characteristics of rheumatoid arthritis (RA) patients who underwent cervical spine surgery using a multicenter observational database. Methods We obtained data from a nationwide observational cohort database of patients with rheumatic diseases (National Database of Rheumatic Diseases by iR-net in Japan (NinJa)) for the fiscal years 2003 to 2011. A total of 39 out of 60 patients who underwent cervical spine surgery for a RA-related cause and whose data were available for two consecutive years (to assess the preoperative patient status) were chosen as cases. Patients with a non-RA-related cause of surgery (e.g., trauma) were excluded. First, we compared the patient characteristics between the cases and total patients in the same fiscal year. Next, 106 eligible controls, who were defined as RA patients enrolled in the same fiscal year as the case subjects, who were matched for age, gender and disease duration (within ±1 year), were selected. We compared the demographic data between the two groups. We also calculated the percentage of patients who underwent cervical spine surgery (surgeries/total number of patients) in fiscal years 2003 to 2011. Results Although the proportion of patients using biologics linearly increased during study period, the percentage of patients undergoing cervical spine surgeries remained unchanged, at approximately 0.15%. These cases had more tender joints (3 vs. 1, p < 0.01) and exhibited a significantly higher Modified Health Assessment Questionnaire (MHAQ) score (1.13 vs. 0.5, p < 0.01), C-reactive protein (CRP) (1.5 vs. 0.36, p < 0.01), and disease activity score (DAS) 28-CRP (3.63 vs. 2.81, p < 0.01) compared to the controls. Conclusions Our study revealed that RA patients requiring cervical spine surgery have a higher disease activity (as represented by the DAS28-CRP) and are more functionally disabled (as represented by the MHAQ) than control patients. PMID

  9. Prognostic Value of Reverse Dipper Blood Pressure Pattern in Chronic Kidney Disease Patients not Undergoing Dialysis: Prospective Cohort Study

    PubMed Central

    Wang, Cheng; Ye, Zengchun; Li, Yan; Zhang, Jun; Zhang, Qunzi; Ma, Xinxin; Peng, Hui; Lou, Tanqi

    2016-01-01

    The “reverse dipping” blood pressure (BP) pattern has been studied among the general population and in individuals suffering from hypertension. However, the prognosis of this pattern in chronic kidney disease (CKD) patients is not known. We monitored BP throughout the day and followed health outcomes in 588 CKD patients admitted to our hospital. Time to all-cause mortality, cardiovascular mortality, renal events and cardiovascular events was recorded. Multivariate-adjusted Cox regression analyses were carried out to detect the prognostic value of a reverse dipping BP pattern. Prevalence of a “dipper”, “non-dipper” and “reverse dippers” was 34.69%, 43.54% and 18.03%, respectively. Patients with a reverse dipping pattern had a higher prevalence of total mortality, cardiovascular mortality, renal events and cardiovascular events than patients with a dipping pattern (P < 0.025). Multivariate-adjusted Cox regression analyses showed that reverse dippers (versus dippers) were associated with a higher risk of total mortality (hazard ratio [HR], 5.08; 95% confidence interval [CI], 1.79~14.47), cardiovascular mortality (4.17; 1.25~13.88), renal events (3.00; 1.59~5.65) and cardiovascular events (4.12; 1.78~9.51) even after adjustment by 24-h systolic BP. These data suggest that a reverse dipping BP pattern, independent of 24-h levels of systolic BP, has prognostic value in CKD patients not undergoing dialysis. PMID:27713498

  10. Antithymocyte globulin for acute-graft-versus-host-disease prophylaxis in patients undergoing allogeneic hematopoietic cell transplantation: a systematic review.

    PubMed

    Kumar, A; Mhaskar, A R; Reljic, T; Mhaskar, R S; Kharfan-Dabaja, M A; Anasetti, C; Mohty, M; Djulbegovic, B

    2012-04-01

    Graft-versus-host-disease (GVHD) is a major complication associated with allogeneic hematopoietic cell transplantation (allo-HCT). Antithymocyte globulin (ATG) is recommended for GVHD prophylaxis following allo-HCT, however, evidence on efficacy of ATG is conflicting. Accordingly, we undertook a systematic review. All phase III randomized controlled trials (RCTs) comparing ATG versus control for prevention of GVHD in patients undergoing allo-HCT were eligible. Medline and Cochrane databases were searched. Data on methodological quality, benefits and harms were extracted for each trial and pooled under a random effects model. Seven RCTs enrolling 733 patients met inclusion criteria. Pooled results showed no difference for overall survival with use of ATG (hazard ratio was 0.91; 95% confidence intervals (CI), 0.75-1.10; P = 0.32). There was a significant benefit for prevention of grade III/IV acute GVHD (risk ratio (RR) = 0.51; 95% CI, 0.27-0.94; P = 0.03). There was no benefit associated with ATG use for prevention of either grade II (RR = 0.79; 95% CI, 0.48-1.30; P = 0.35) or grade I acute GVHD (RR = 1.42; 95% CI, 0.75-2.69; P = 0.28). Use of ATG was not associated with significant reduction in non-relapse mortality (RR = 0.74; 95% CI, 0.53-1.03; P = 0.08). Future trials with adequate sample size are required to provide more definitive answers.

  11. Cross-sectional imaging to evaluate the extent of regional nodal disease in breast cancer patients undergoing neoadjuvant systemic therapy.

    PubMed

    Anderson, Tara L; Glazebrook, Katrina N; Murphy, Brittany L; Viers, Lyndsay D; Hieken, Tina J

    2017-04-01

    Cross-sectional imaging often is performed in breast cancer patients undergoing neoadjuvant systemic therapy (NST) and may identify level III axillary and extra-axillary nodal disease. Our aim was to investigate associations of radiologic nodal staging with pathological N (pN) stage at operation and to explore how this might aid surgical and radiotherapy treatment planning. With IRB approval, we reviewed pre-treatment breast MRI, PET/CT, and CT imaging and clinicopathologic data on 348 breast cancer patients with imaging available for review undergoing NST followed by operation at our institution 1/2008-9/2013. We defined abnormal lymph node findings on MRI, CT, and PET/CT to include cortical thickening, FDG-avidity and loss of fatty hilum. Patients were assigned a radiologic nodal (rN) stage based on imaging findings. Statistical analysis was performed using JMP 10.1 software RESULTS: Pre-NST imaging included axillary ultrasound in 338 patients (97%), breast MRI in 305 (88%) and PET/CT or CT in 215 (62%). 213 patients (61%) were biopsy-proven axillary lymph node-positive (LN+) pre-treatment. cT stage was T1 in 9%, T2 in 49%, T3 in 29%, T4 in 12%; median tumor size was 4cm. Pre-treatment rN stage across all the patients was rN0 in 86 (25%), rN1 in 173 (50%), and rN3 in 89 (26%). rN3 disease included level III axillary, supraclavicular and suspicious internal mammary lymph nodes in 47 (53%), 32 (37%) and 45 (52%), respectively. Of patients LN+ at diagnosis, 78 (37%) were rN3. After NST, 162 patients (47%) were node-positive at operation with a median (mean) of 3 (5.9±0.4) positive lymph nodes including 128 of 213 (60%) LN+ at diagnosis. Pre-NST rN stage correlated with the likelihood and extent of axillary disease at operation, p=0.002. Fifty four of 89 rN3 patients (61%) were node-positive at operation with a median (mean) of 5 (8±1) positive nodes. rN3 patients had larger nodal metastases (median 9 vs 6mm) and more frequent extranodal extension (61% vs 43%) than

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

    PubMed

    Chen, Julie Y; Choi, Edmond P H; Wan, Eric Y F; Chan, Anca K C; Tsang, Joyce P Y; Chan, Karina H Y; Lo, W K; Lui, S L; Chu, W L; Lam, Cindy L K

    2016-01-01

    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. 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. 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. 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.

  13. 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

  14. 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

  15. HDL Cholesterol Level Is Associated with Contrast Induced Acute Kidney Injury in Chronic Kidney Disease Patients Undergoing PCI

    PubMed Central

    Park, Hoon Suk; Kim, Chan Joon; Hwang, Byung-Hee; Kim, Tae-Hoon; Koh, Yoon Seok; Park, Hun-Jun; Her, Sung-Ho; Jang, Sung Won; Park, Chul-Soo; Lee, Jong Min; Kim, Hee-Yeol; Jeon, Doo Soo; Kim, Pum-Joon; Yoo, Ki-Dong; Chang, Kiyuk; Jin, Dong Chan; Seung, Ki-Bae

    2016-01-01

    Chronic kidney disease (CKD) is a significant risk factor for contrast induced acute kidney injury (CI-AKI) after percutaneous coronary intervention (PCI). This study included 1592 CKD patients extracted from a prospective multicenter, all comer-based registry of patients undergoing PCI. In multivariate logistic analysis for CI-AKI development, a significant linear trend was observed between the quartiles of HDL-C (quartile 1 vs. 2: odds ratio [OR], 0.716; 95% confidence interval [CI], 0.421–1.219; quartile 1 vs. 3: OR, 0.534; 95% CI, 0.301–0.947; quartile 1 vs. 4: OR, 0.173; 95% CI, 0.079–0.377; P for trend < 0.001). HDL-C quartiles were also negatively correlated with the incidence of CI-AKI; 19.0%, 12.1%, 8.7%, and 3.7% for quartile 1(Q1) (<34 mg/dL), Q2 (34–40 mg/dL), Q3 (40–48 mg/dL), and Q4 (>48 mg/dL) respectively (P < 0.001 overall and for the trend). Multivariate Cox regression analysis for the long term mortality, the highest HDL-C quartile was associated with decreased mortality compared with the lowest HDL-C quartile (hazard ratio [HR] 0.516, 95% CI, 0.320–0.832, P = 0.007). Our study suggests more intensive strategies should be considered for preventing CI-AKI in CKD patients with low serum HDL-C level who is planned for PCI. PMID:27775043

  16. One year efficacy and safety of lanthanum carbonate for hyperphosphatemia in Japanese chronic kidney disease patients undergoing hemodialysis.

    PubMed

    Shigematsu, Takashi

    2010-02-01

    Lanthanum carbonate is a non-calcium-based phosphate binder for hyperphosphatemia in patients with chronic kidney disease (CKD). The efficacy and safety of lanthanum carbonate (LaC) on hyperphosphatemia in patients has been well documented in clinical trials in Western countries and recent relatively short-term clinical trials in Japan. Evidence supporting its safety and efficacy in Japanese patients for longer-term treatment is now desired for clinical practice. A non-controlled, open-label, multicenter, one year study of LaC to assess safety and its effect on the levels of serum phosphate, serum calcium and parathyroid hormone was performed with Japanese dialysis patients. Lanthanum carbonate was administered to patients at variable doses for a period of 46-52 weeks. Evaluation of the safety and efficacy of LaC in reducing serum phosphate was performed, in addition to extensive and systematic monitoring of the laboratory parameters related to bone turnover and cardiac health. A significant reduction in the serum phosphate level was demonstrated throughout the treatment period (P < 0.05), without any increase in the frequency or severity of drug-related adverse events such as vomiting, nausea, and stomach discomfort. There was no clinically relevant change in vital signs, or electrocardiograms for a period. The profiles for parathyroid hormone, bone alkaline phosphates, and osteocalcin were stable in the patients concomitantly treated with vitamin D. This study provides further evidence that the administration of LaC over a period of one year is safe and effective for the reduction of serum phosphate levels in CKD patients undergoing hemodialysis.

  17. Predictors of Discharge to a Nonhome Facility in Patients Undergoing Lumbar Decompression Without Fusion for Degenerative Spine Disease.

    PubMed

    Murphy, Meghan E; Maloney, Patrick R; McCutcheon, Brandon A; Rinaldo, Lorenzo; Shepherd, Daniel; Kerezoudis, Panagiotis; Gilder, Hannah; Ubl, Daniel S; Crowson, Cynthia S; Freedman, Brett A; Habermann, Elizabeth B; Bydon, Mohamad

    2017-10-01

    Patients recovering from decompressive laminectomy without fusion may require assistance with activities of daily living and physical/occupational therapy upon hospital discharge. To examine comorbidities and perioperative characteristics of patients undergoing lumbar decompression for associations with discharge status using a multicenter database. A multicenter database was used for this retrospective cohort analysis. Patients admitted from home with degenerative spine disease for lumbar decompression without fusion were included. Thirty-day outcomes and operative characteristics were compared as a function of patient discharge using chi-square and Wilcoxon Rank Sum tests. Multivariable logistic regression was used to determine factors associated with discharge to a nonhome facility. Of the 8627 patients included for analysis, 9.7% were discharged to a nonhome facility. On multivariable analysis, age (85+ vs <65, odds ratio [OR] 13.59), number of levels of decompression (3+ vs 1, OR 1.75), African American race vs Non-Hispanic or Hispanic White (OR 1.87), female vs male gender (OR 1.97), body mass index (BMI) (40+ vs 18.5-24.9, OR 1.74), American Society of Anesthesiologists physical classification status (4 vs 1 or 2, OR 2.35), hypertension (OR 1.29), dependent functional status (OR 3.92), diabetes (OR 1.47), smoking (OR 1.40), hematocrit (<35 vs 35+, OR 1.76), international normalized ratio (≥1.3 vs <1.3, OR 2.32), and operative time (3+ h vs <1 h, OR 5.34) were significantly associated with an increased odds of discharge to nonhome facilities. Preoperative status and operative course variables can influence discharge disposition in lumbar decompression patients. Identifying specific factors that contribute to a greater likelihood of dismissal to skilled facility or rehabilitation unit can further inform both surgeons and patients during preoperative counseling and disposition planning.

  18. Association of catechol-O-methyltransferase genetic variants with outcome in patients undergoing surgical treatment for lumbar degenerative disc disease.

    PubMed

    Dai, Feng; Belfer, Inna; Schwartz, Carolyn E; Banco, Robert; Martha, Julia F; Tighioughart, Hocine; Tromanhauser, Scott G; Jenis, Louis G; Kim, David H

    2010-11-01

    Surgical treatment for lumbar degenerative disc disease (DDD) has been associated with highly variable results in terms of postoperative pain relief and functional improvement. Many experts believe that DDD should be considered a chronic pain disorder as opposed to a degenerative disease. Genetic variation of the catechol-O-methyltransferase (COMT) gene has been associated with variation in human pain sensitivity and response to analgesics in previous studies. To determine whether genetic variation of COMT is associated with clinical outcome after surgical treatment for DDD. Prospective genetic association study. Sixty-nine patients undergoing surgical treatment for lumbar DDD. Diagnosis was based on documentation of chronic disabling low back pain (LBP) present for a minimum of 6 months and unresponsive to supervised nonoperative treatment, including activity modification, medication, physical therapy, and/or injection therapy. Plain radiographs and magnetic resonance imaging revealed intervertebral disc desiccation, tears, and/or collapse without focal herniation, nerve root compression, stenosis, spondylolisthesis, spondylolysis, or alternative diagnoses. Oswestry Disability Index (ODI) and visual analog score (VAS) for LBP. Surgical treatment included 65 instrumented fusions and four disc arthroplasty procedures. All patients completed preoperative and 1-year postoperative ODI questionnaires. DNA was extracted from a sample of venous blood, and genotype analysis was performed for five common COMT single nucleotide polymorphisms (SNPs). Potential genetic association between these COMT SNPs and the primary outcome variable, 1-year change in ODI, was investigated using both single-marker and haplotype association analyses. Association with VAS scores for LBP was analyzed as a secondary outcome variable. Single-marker analysis revealed that the COMT SNP rs4633 was significantly associated with greater improvement in ODI score 1 year after surgery (p=.03), with

  19. Comparison of isoflurane and propofol for maintenance of anesthesia in dogs with intracranial disease undergoing magnetic resonance imaging.

    PubMed

    Caines, Deanne; Sinclair, Melissa; Valverde, Alexander; Dyson, Doris; Gaitero, Luis; Wood, Darren

    2014-09-01

    To compare isoflurane and propofol for maintenance of anesthesia and quality of recovery in client-owned dogs with intracranial disease undergoing magnetic resonance imaging (MRI). Prospective, randomized, clinical trial. Twenty-five client-owned dogs with intracranial pathology, 13 females and 12 males, ages 11 months to 13 years, weighing between 3.0 and 48.0 kg. Each dog was randomly assigned to receive propofol or isoflurane for maintenance of anesthesia. All dogs were not premedicated, were administered propofol intravenously to effect for induction, intubated and mechanically ventilated to maintain an end-tidal carbon dioxide tension 30-35 mmHg (4.0-4.7 kPa). Temperature and cardiac output were measured pre- and post-MRI. Scores for mentation, neurological status, ease of maintenance, and recovery were obtained pre- and post-anesthesia. Pulse oximetry, end-tidal gases, arterial blood pressure, heart rate (HR) and requirements for dopamine administration to maintain mean arterial pressure (MAP) >60 mmHg were recorded throughout anesthesia. End-tidal isoflurane concentration was 0.73 ± 0.35% and propofol infusion rate was 292 ± 119 μg kg(-1)  minute(-1) . Cardiac index was higher, while HR was lower, with propofol than isoflurane in dogs younger than 5 years, but not in older dogs. Dogs maintained with isoflurane were 14.7 times more likely to require dopamine than propofol dogs. Mentation and maintenance scores and temperature were not different. MAP and diastolic arterial pressure were higher in the propofol group. Recovery scores were better with propofol, although times to extubation were similar. Change in neurological score from pre- to post-anesthesia was not different between treatments. Dogs maintained with propofol during MRI had higher arterial pressures, decreased requirements for dopamine, and better recovery scores, compared to dogs maintained with isoflurane. Propofol anesthesia offered cardiovascular and recovery advantages over

  20. Pulmonary gas exchange and plasma lactate in horses with gastrointestinal disease undergoing emergency exploratory laparotomy: a comparison with an elective surgery horse population.

    PubMed

    McCoy, Annette M; Hackett, Eileen S; Wagner, Ann E; Mama, Khursheed R; Hendrickson, Dean A

    2011-07-01

    To characterize pulmonary gas exchange and arterial lactate in horses with gastrointestinal disease undergoing anesthesia, compared with elective surgical horses, and to correlate these variables with postoperative complications and mortality. Prospective clinical study. Horses undergoing emergency laparotomy for acute intestinal disease (n = 50) and healthy horses undergoing elective surgery in dorsal recumbency (n = 20). Arterial blood gas analysis was performed at predetermined intervals on horses undergoing a standardized anesthetic protocol. Alveolar-arterial oxygen gradient was calculated. Predictive factors for postoperative complications and death in colic horses were determined. Arterial oxygen tension (P(a) O(2)) varied widely among horses in both groups. P(a) O(2) significantly increased in the colic group after exteriorization of the ascending colon. P(a) O(2) and alveolar-arterial oxygen gradient were not significantly different between groups, and neither were correlated with horse outcome. Arterial lactate in recovery ≥ 5 mmol/L was associated with a 2.25 times greater relative risk of complications and lactate ≥ 7 mmol/L was associated with a 10.5 times higher relative risk of death. Colic horses in this population were not more likely to be hypoxemic than elective horses, nor was gas exchange impaired to a greater degree in colic horses relative to controls. Arterial lactate sampled immediately after anesthetic recovery was predictive for postoperative complications and death. © Copyright 2011 by The American College of Veterinary Surgeons.

  1. MRI texture analysis (MRTA) of T2-weighted images in Crohn's disease may provide information on histological and MRI disease activity in patients undergoing ileal resection.

    PubMed

    Makanyanga, Jesica; Ganeshan, Balaji; Rodriguez-Justo, Manuel; Bhatnagar, Gauraang; Groves, Ashley; Halligan, Steve; Miles, Ken; Taylor, Stuart A

    2017-02-01

    To associate MRI textural analysis (MRTA) with MRI and histological Crohn's disease (CD) activity. Sixteen patients (mean age 39.5 years, 9 male) undergoing MR enterography before ileal resection were retrospectively analysed. Thirty-six small (≤3 mm) ROIs were placed on T2-weighted images and location-matched histological acute inflammatory scores (AIS) measured. MRI activity (mural thickness, T2 signal, T1 enhancement) (CDA) was scored in large ROIs. MRTA features (mean, standard deviation, mean of positive pixels (MPP), entropy, kurtosis, skewness) were extracted using a filtration histogram technique. Spatial scale filtration (SSF) ranged from 2 to 5 mm. Regression (linear/logistic) tested associations between MRTA and AIS (small ROIs), and CDA/constituent parameters (large ROIs). Skewness (SSF = 2 mm) was associated with AIS [regression coefficient (rc) 4.27, p = 0.02]. Of 120 large ROI analyses (for each MRI, MRTA feature and SSF), 15 were significant. Entropy (SSF = 2, 3 mm) and kurtosis (SSF = 3 mm) were associated with CDA (rc 0.9, 1.0, -0.45, p = 0.006-0.01). Entropy and mean (SSF = 2-4 mm) were associated with T2 signal [odds ratio (OR) 2.32-3.16, p = 0.02-0.004], [OR 1.22-1.28, p = 0.03-0.04]. MPP (SSF = 2 mm) was associated with mural thickness (OR 0.91, p = 0.04). Kurtosis (SSF = 3 mm), standard deviation (SSF = 5 mm) were associated with decreased T1 enhancement (OR 0.59, 0.42, p = 0.004, 0.007). MRTA features may be associated with CD activity. • MR texture analysis features may be associated with Crohn's disease histological activity. • Texture analysis features may correlate with MR-dependent Crohn's disease activity scores. • The utility of MR texture analysis in Crohn's disease merits further investigation.

  2. A Dipeptidyl Peptidase-4 Inhibitor, Teneligliptin, Decreases Plasma Triglyceride-Rich Lipoprotein Remnants in Diabetic Patients with Chronic Kidney Disease Undergoing Hemodialysis.

    PubMed

    Homma, Koichiro; Yoshizawa, Joe; Shiina, Yutaka; Ozawa, Hideki; Igarashi, Muneki; Matsuoka, Tadashi; Sasaki, Junichi; Yoshizawa, Mamoru; Homma, Yasuhiko

    2017-06-02

    A high plasma level of remnant-like particle cholesterol (RLP-C), which is equivalent to triglyceride-rich lipoprotein remnant, is an important coronary risk marker. RLP-C level is high, independent of other plasma lipids, in patients with chronic kidney disease (CKD) undergoing hemodialysis. The effect of teneligliptin, a dipeptidyl peptidase (DPP)-4 inhibitor, on plasma levels of RLP-C in patients with diabetes mellitus and CKD under hemodialysis was studied. Teneligliptin 20 mg/day was administered to 15 patients with diabetes and CKD undergoing hemodialysis for 12 weeks. Ten patients with diabetes and CKD undergoing hemodialysis were allocated to the control group. Blood was sampled following a 12-h fast. Fasting plasma glucose (FPG), C-peptide, triglyceride, low-density lipoprotein (LDL)-cholesterol (C), high-density lipoprotein (HDL)-C, RLP-C, apolipoprotein (apo) B, oxidized LDL, lipoprotein lipase, and glycated hemoglobin (HbA1c) were measured. HbA1c decreased in the teneligliptin group but significantly increased in the control group. FPG and RLP-C significantly decreased in the teneligliptin group. Plasma lipoprotein-related parameters except RLP-C were not affected by teneligliptin treatment. Teneligliptin treatment significantly reduced plasma levels of RLP-C, FPG, and HbA1c in patients with diabetes with CKD who are undergoing hemodialysis.

  3. Prevalence of Earlobe Creases and Their Association With History of Cardiovascular Disease in Patients Undergoing Hemodialysis: A Cross-Sectional Study.

    PubMed

    Wakasugi, Minako; Kazama, Junichiro James; Kawamura, Kazuko; Yamamoto, Suguru; Nagai, Masaaki; Omori, Kentaro; Yokota, Saori; Fujikawa, Hirokazu; Aoike, Ikuo; Omori, Tsukasa; Narita, Ichiei

    2017-10-01

    Earlobe creases are surrogate markers for high risk of cardiovascular disease. There is no data concerning earlobe creases among hemodialysis patients, who have an increased risk of cardiovascular disease. A cross-sectional study was conducted to determine the prevalence of earlobe creases and their association with prevalent cardiovascular disease among hemodialysis patients. Patients undergoing hemodialysis were recruited from five outpatient hemodialysis centers. Both earlobes were photographed during a dialysis session with the patient in a supine position and the photos evaluated independently by two experienced nephrologists blinded to the participants' clinical characteristics. Prevalent cardiovascular diseases were defined as a history of myocardial infarction, cerebrovascular accident, or peripheral vascular disease. Sensitivity, specificity, and positive and negative predictive values for detection of prevalent cardiovascular disease were calculated. Logistic analysis was used to examine the association between earlobe creases and prevalent cardiovascular disease. Earlobe creases were identified in 24.5% of 330 hemodialysis patients (200 men; mean age, 67.8 years). The prevalence of earlobe creases increased with age for men (P for trend <0.0001), but not for women (P for trend = 0.07). Sensitivity, specificity, and positive and negative predictive values were 30.9% (95% confidence interval, 21.9-41.6), 77.5% (71.9-82.3), 30.9% (21.9-41.6), and 77.5% (71.9-82.3), respectively. Multivariate logistic analyses indicated the prevalence of earlobe crease was not associated with prevalent cardiovascular diseases. The prevalence is similar to that previously reported for Japanese individuals not undergoing dialysis. No association between earlobe creases and prevalent cardiovascular diseases was identified. © 2017 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

  4. 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

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

    2013-09-01

    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). Among 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 United States (as opposed to Mexico) positively influenced the likelihood of participating. Our data suggest 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. © 2013. Published by Elsevier Inc. All rights reserved.

  5. 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

  6. Preliminary evaluation of a microtransesophageal probe in neonates and young infants undergoing surgery for congenital heart disease

    PubMed Central

    Pavithran, Sreeja; Natarajan, Kanagarajan; Vishwambaran, Bijesh; Arke, Avinash Dayalal; Sivakumar, Kothandam

    2014-01-01

    Background: The larger size of the currently available transesophageal echocardiography (TEE) probes limits their use to relatively older infants undergoing cardiac surgery. In very young neonates and infants, epicardial echocardiogram is used to assess postoperative residual defects. Recently, a miniaturized microTEE probe compatible in neonates has been introduced for clinical use. We evaluated the use of this probe in small infants undergoing cardiac surgery. Materials and Methods: Thirty-three consecutive neonates and infants undergoing cardiac surgery at our institution were included in the study. Intraoperative echocardiography with Philips s8-3t microTEE probe done using IE33 platform was utilized to study the preoperative anatomy and assess postoperative results. Results: Thirty-three patients aged 3 days-2 years (mean 5.1 months) and weighing 2.5-11 kg (mean 4.4 kg) underwent perioperative evaluation using the microTEE probe. Good quality two-dimensional and color Doppler images were obtained in all patients. There were no complications related to the probe insertion or manipulation. The findings on microTEE led to revision of surgery in five patients. Certain echocardiographic parameters that could never be recorded with epicardial echocardiogram could be easily seen in microTEE. Conclusion: On preliminary evaluation, the microTEE probe provided good quality images in very small infants who were not amenable for transesophageal echocardiographic evaluation so far. The probe could be used safely in small infants without complications. It appears to be a promising imaging modality in the perioperative assessment of young infants undergoing cardiac surgery, in whom intraoperative epicardial echocardiography is currently the only tool. PMID:25298691

  7. Should studies of patients undergoing coronary angiography be used to evaluate the role of behavioral risk factors for coronary heart disease?

    PubMed

    Pickering, T G

    1985-09-01

    Several studies have attempted to assess the contribution of behavioral factors to coronary heart disease by relating the Type A behavior pattern to the extent of coronary artery disease (CAD) in patients undergoing coronary angiography. Although the earlier studies gave positive results, more recent results have been negative; overall the results are confusing. These differences cannot be easily explained by differences in study design. Possible confounding factors which may limit the usefulness of such studies include biased subject selection (approximately 70% of subjects were classified as Type A, and 70% had CAD) and the effects of beta blockers. Furthermore, other studies of similar design which have attempted to relate the three major risk factors to CAD have also yielded conflicting results: an association has been demonstrated consistently with cholesterol, less consistently with smoking, and not at all with hypertension. It is argued that such studies are not well suited to investigating relationships between behavioral factors and coronary heart disease.

  8. Microbiological and aMMP-8 findings depending on peri-implant disease in patients undergoing supportive implant therapy.

    PubMed

    Ziebolz, Dirk; Schmalz, Gerhard; Gollasch, Daniel; Eickholz, Peter; Rinke, Sven

    2017-02-21

    The aim of this study was to evaluate microbiological findings and aMMP-8 level of peri-implant mucositis (M) and peri-implantitis (P) in patients undergoing supportive implant therapy (SIT). Eighty-nine patients with 171 implants were included. The case definitions were as follows: M: PPD ≥4mm, BOP; P: PPD≥4mm, BOP, radiographic bone loss ≥3.5mm. Samples of peri-implant sulcular fluid (PISF) were taken from all peri-implant pockets at each implant to detect periodontal pathogens using PCR and aMMP-8 level with ELISA. Only Treponema denticola (Td) and Prevotella intermedia (Pi) showed significantly higher prevalence in P (healthy implants [HI]: Td=27%, Pi=17%; M: Td=26%, Pi=15%; P: Td and Pi=50%; P<0.05). The mean aMMP-8 level at implant sites did not show any significant difference (P=0.05) among HI (5.2±8.1), M (9.9±19.0), and P (4.9±7.7). Microbiological findings and aMMP-8 levels are not reliable criteria to distinguish between HI, M, and P in patients undergoing SIT.

  9. Low Recent Protein Intake Predicts Cancer-Related Fatigue and Increased Mortality in Patients with Advanced Tumor Disease Undergoing Chemotherapy.

    PubMed

    Stobäus, Nicole; Müller, Manfred J; Küpferling, Susanne; Schulzke, Jörg-Dieter; Norman, Kristina

    2015-01-01

    Cancer patients, in general, suffer from anorexia hence diminished nutritional intake. In a prospective observational study, we investigated the impact of recent energy and protein intake on cancer-related fatigue and 6-month mortality in patients undergoing chemotherapy. Recent protein and energy intake was assessed by 24-h recall in 285 patients. Cancer-related fatigue was determined by Brief Fatigue Inventory, and fat free mass index (FFMI) was assessed with bioelectrical impedance analysis. Symptoms with the validated German version of European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (30 questions) and 6-month mortality was documented. Risk factors of cancer-related fatigue and predictors of mortality were investigated with logistic regression analysis and stepwise Cox regression analysis, respectively. Low protein intake (<1 g/kg body weight) was found in 66% of patients, who were characterized by higher age, weight, and body mass index. Recent protein intake emerged as the strongest contributor to cancer-related fatigue followed by nausea/vomiting, insomnia, and age. Reduced protein intake, male sex, number of comorbidities, and FFMI were identified as significant predictors for increased 6-month mortality. In conclusion, a low recent protein intake assessed by 24-h recall is associated with a more than twofold higher risk of cancer-related fatigue and 6-month mortality. Every effort should be taken to assess and guarantee proper nutritional intake in patients undergoing chemotherapy.

  10. Role of simultaneous carotid ultrasound in patients undergoing stress echocardiography for assessment of chest pain with no previous history of coronary artery disease.

    PubMed

    Ahmadvazir, Shahram; Zacharias, Konstantinos; Shah, Benoy N; Pabla, Jatinder S; Senior, Roxy

    2014-08-01

    We prospectively explored prevalence of carotid disease (CD), its independent association with coronary artery disease (CAD) and outcome as well as potential impact on management, in patients undergoing stress echocardiography (SE) for new onset chest pain without known CAD. Accordingly, 591 consecutive patients referred for SE underwent carotid ultrasound. Carotid disease was defined as carotid intima-media thickness (C-IMT) >75th percentile for age and sex and/or presence of plaque. Myocardial ischemia was demonstrated in only a minority (11%), but there was a high prevalence of CD (70%). Incidence of CD was similar in patients with and without ischemia (76% versus 69%, P = .26). Carotid data led to reclassification of Framingham risk score categories in 65% of patients as well as more than a third of negative SE patients potentially benefitting from primary prevention therapy. Of the 83 patients undergoing coronary arteriography, 59 (71%) demonstrated coronary atherosclerosis (any atheroma) and 33 (40%) CAD. Positive predictive value of SE for CAD was 56%, but presence of carotid plaque improved it to 70%. Although both CD and plaque showed association with CAD and revascularization, after adjustment for conventional risk factors, only carotid plaque maintained significant association (P = .024 and P = .023, respectively). There is significantly higher prevalence of CD compared with myocardial ischemia in patients undergoing SE and carotid ultrasound for suspected CAD. This can lead to significant Framingham risk score reclassification with important primary prevention implications. Carotid plaque is superior to clinical assessment for the prediction of CAD and improves positive predictive value of SE for CAD in these patients. Copyright © 2014 Mosby, Inc. All rights reserved.

  11. [Prophylaxis against Toxoplasma gondii disease in pediatric and adult patients undergoing solid organ and hematopoietic stem cells transplantation].

    PubMed

    Payá, Ernesto; Noemí, Isabel; Tassara, Renzo; Catalán, Paula; Avilés, Carmen L

    2012-09-01

    Toxoplasmosis is a widely distributed zoonosis produced by the parasite T. gondii. In Chile the seroprevalence has been estimated between 20-37% in general population. Defined risk groups acquire or reactivate the infection by T. gondii in patients undergoing SOT and HSCT are: heart transplant or heart-lung with D (+) and R (-), allogeneic HSCT with R (+), HSCT with cord cells, GVHD, history of previous clinical toxoplasmosis and use of corticosteroids for prolonged periods or in high doses. Hand washing, hygiene in food handling and weekly post-transplant surveillance since day 15 post transplant for six months, are universally recommended. All patients with SOT and HSCT, regardless of risk, should receive prophylaxis with cotrimoxazole and require no another specific prophylaxis against T. gondii (A2). It is particularly important in high-risk patients who cannot receive cotrimoxazole prophylaxis establish specific alternative against T. gondii (B3).

  12. Risk of cytomegalovirus reactivation in patients with immune-mediated inflammatory diseases undergoing biologic treatment: a real matter?

    PubMed

    Mencarini, J; Spinicci, M; Bartalesi, F

    2016-12-16

    The use of biological agents has grown exponentially in immune-mediated inflammatory diseases (IMID), often achieving a good control of disease progression and improving patients' quality of life. However, their use resulted in an increased risk of adverse events, including reactivation of chronic/latent infectious diseases. As for the risk of Cytomegalovirus (CMV) reactivation, very few data are available. We reviewed the literature reporting cases of CMV infection in IMID patients during biological therapy. Although the risk of CMV reactivation cannot be excluded, we concluded that there is no evidence to warrant CMV screening before starting a biological agent.

  13. Comparison of the Effects of Dexmedetomidine and Propofol on Hemodynamics and Oxygen Balance in Children with Complex Congenital Heart Disease Undergoing Cardiac Surgery.

    PubMed

    Cheng, Xinqi; Zuo, Youmei; Zhao, Qing; Gu, Erwei; Huang, Yue

    2015-01-01

    The aim of this study was to compare the effects of anesthesia by dexmedetomidine and propofol on the hemodynamics and oxygen balance in children with complex congenital heart disease who were undergoing cardiac surgery. Fifty-seven children were randomized to receive either a continuous infusion of propofol (6-8 mg/kg/h) or dexmedetomidine (0.5-0.7 μg/kg/h) after anesthesia induction. Hemodynamic data were recorded. Oxygen balance parameters were assessed at baseline after midazolam sedation, before and immediately after skin incisions were made, after sternotomy, 5 minutes after protamine administration, and at the end of surgery. Compared with the dexmedetomidine group, the propofol group exhibited decreases in blood pressure, cardiac output, and cardiac index before skin incision (P < .05) and increases in blood pressure, heart rate, cardiac output, and cardiac index after sternotomy (P < .01). However, very similar trends in oxygen dynamics were obtained in both groups (P > .05), and the cardiac index was not correlated with total oxygen consumption (r = -0.109, P = .066) or the oxygen extraction ratio (r = -0.107, P = .072). Dexmedetomidine infusion may be superior to propofol anesthesia in children with complex congenital heart disease who are undergoing cardiopulmonary bypass because dexmedetomidine was associated with less variability in heart rate or blood pressure during surgery. However, the oxygen balance was similar when either agent was used. © 2014 Wiley Periodicals, Inc.

  14. Risk factors for unfavourable postoperative outcome in patients with Crohn's disease undergoing right hemicolectomy or ileocaecal resection An international audit by ESCP and S-ECCO.

    PubMed

    2017-09-15

    Patient and disease-related factors, as well as operation technique all have the potential to impact on postoperative outcome in Crohn's disease. The available evidence is based on small series and often displays conflicting results. To investigate the effect of pre- and intra-operative risk factors on 30-day postoperative outcome in patients undergoing surgery for Crohn's disease. International prospective snapshot audit including consecutive patients undergoing right hemicolectomy or ileocaecal resection. This study analysed a subset of patients who underwent surgery for Crohn's disease. The primary outcome measure was the overall Clavien-Dindo postoperative complication rate. The key secondary outcomes were anastomotic leak, re-operation, surgical site infection and length of stay at hospital. Multivariable binary logistic regression analyses were used to produce odds ratios (OR) and 95% confidence intervals (CI). Three hundred and seventy five resections in 375 patients were included. The median age was 37 and 57.1% were female. In multivariate analyses, postoperative complications were associated with preoperative parenteral nutrition (OR 2.36 95% CI 1.10-4.97)], urgent/expedited surgical intervention (OR 2.00, 95% CI 1.13-3.55) and unplanned intraoperative adverse events (OR 2.30, 95% CI 1.20-4.45). The postoperative length of stay in hospital was prolonged in patients who received preoperative parenteral nutrition (OR 31, CI [1.08-1.61]) and those who had urgent/expedited operations (OR 1.21, CI [1.07-1.37]). Preoperative parenteral nutritional support, urgent/expedited operation and unplanned intraoperative adverse events were associated with unfavourable postoperative outcome. Enhanced preoperative optimization and improved planning of operation pathways and timings may improve outcomes for patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  15. Substitution with Alternative Anti-TNFα Therapy (SAVANT)-Outcomes of a Crohn's Disease Cohort Undergoing Substitution Therapy with Certolizumab.

    PubMed

    Boktor, Moheb; Motlis, Andrew; Aravantagi, Avinash; Sheth, Ankur; Jordan, Paul; Morris, James; Manas, Kenneth; Hussain, Nazneen; Cvek, Urska; Trutschl, Marjan; Becker, Felix; Alexander, J Steven

    2016-06-01

    Biological therapy targeting tumor necrosis factor-alfa has revolutionized the treatment of Crohn's disease (CD). Our study retrospectively reviewed clinical outcomes of 60 patients administratively substituted from Infliximab or Adalimumab to Certolizumab. Maintenance of disease and failure rates after substitution of anti-tumor necrosis factor-alfa agents in CD patients were monitored over 1 year, and this is the first outcomes study of patients maintained on Infliximab or Adalimumab substituted to Certolizumab. A hospital pharmacy directive required all patients on biological therapy to be administratively substituted to Certolizumab therapy. This single-center retrospective analysis initially included 68 CD patients presenting at Louisiana State University Health Sciences Center-Shreveport. Clinical, endoscopic, and serologic data were compared at baseline and at 4 intervals over 1 year. Of 60 enrolled CD patients, 45 (75%) successfully transitioned to Certolizumab and had stable disease at 1 year. Of the 15 (25%) patients who "failed" substitution at 1 year, 5 were returned to Adalimumab and 7 to Infliximab; 3 were maintained on steroids awaiting subsequent therapy. Importantly, when patients were segregated on the basis of initial disease control, it was found that 3 (12.5%) previously well-controlled patients failed therapy, whereas 12 (33.3%) who initially had active disease failed Certolizumab substitution. Our study found that 25% of CD patients substituted to Cimzia failed substitution, whereas 75% still exhibited a good clinical response with stable disease at 1 year. Our findings indicate that disease status and behavior at the time of biological substitution may predict therapeutic responsiveness.

  16. Icodextrin eliminates phosphate and ameliorates cardiac hypertrophy and valvular calcification in patients with end-stage renal disease and diabetes mellitus undergoing peritoneal dialysis.

    PubMed

    Hiramatsu, Takeyuki; Hayasaki, Takahiro; Hobo, Akinori; Furuta, Shinji; Kabu, Koki; Tonozuka, Yukio; Iida, Yoshiyasu

    2013-01-01

    Among end-stage renal disease (ESRD) patients, cardiovascular disease is a common comorbidity and one of most important factors affecting clinical prognosis. Calcium deposition has been reported to correlate with plasma phosphate. Icodextrin (Ico)-based peritoneal dialysis (PD) has many advantages over glucose (Glu)-based PD. We aimed to identify factors that suppress arteriosclerosis and valvular disease in patients with ESRD and diabetes mellitus (DM) undergoing Ico-based PD. In this retrospective study, we evaluated the effects of Ico-based PD (n = 20) on phosphate elimination and cardiovascular disease progression in patients with ESRD andDM, and we compared the results with those for Glu-based PD (n = 20). Left ventricular mass index (LVMI) and aortic valve calcification (AVC) score were significantly decreased and daily phosphate elimination was significantly increased in the Ico group compared with the Glu group. Furthermore, mean daily phosphate elimination was significantly and negatively correlated with the amelioration in LVMI and AVC score. Our study suggests that, compared with glucose, icodextrin has the ability to eliminate more phosphate from the body, indicating that phosphate elimination might potentially be a means of controlling cardiovascular disease in PD patients with DM.

  17. Brain transcriptomes of harbor seals demonstrate gene expression patterns of animals undergoing a metabolic disease and a viral infection

    PubMed Central

    Vega Thurber, Rebecca L.

    2016-01-01

    Diseases of marine mammals can be difficult to diagnose because of their life history and protected status. Stranded marine mammals have been a particularly useful resource to discover and comprehend the diseases that plague these top predators. Additionally, advancements in high-throughput sequencing (HTS) has contributed to the discovery of novel pathogens in marine mammals. In this study, we use a combination of HTS and stranded harbor seals (Phoca vitulina) to better understand a known and unknown brain disease. To do this, we used transcriptomics to evaluate brain tissues from seven neonatal harbor seals that expired from an unknown cause of death (UCD) and compared them to four neonatal harbor seals that had confirmed phocine herpesvirus (PhV-1) infections in the brain. Comparing the two disease states we found that UCD animals showed a significant abundance of fatty acid metabolic transcripts in their brain tissue, thus we speculate that a fatty acid metabolic dysregulation contributed to the death of these animals. Furthermore, we were able to describe the response of four young harbor seals with PhV-1 infections in the brain. PhV-1 infected animals showed a significant ability to mount an innate and adaptive immune response, especially to combat viral infections. Our data also suggests that PhV-1 can hijack host pathways for DNA packaging and exocytosis. This is the first study to use transcriptomics in marine mammals to understand host and viral interactions and assess the death of stranded marine mammals with an unknown disease. Furthermore, we show the value of applying transcriptomics on stranded marine mammals for disease characterization. PMID:28028481

  18. Prediction of presence of kidney disease in a general patient population undergoing intravenous iodinated contrast enhanced computed tomography.

    PubMed

    Moos, Shira I; Stoker, Jaap; Nagan, Gajenthiran; de Weijert, Roderick S; van Vemde, David N H; Bipat, Shandra

    2014-06-01

    To assess which risk factors can be used to reduce superfluous estimated glomerular filtration rate (eGFR) measurements before intravenous contrast medium administration. In consecutive patients, all decreased eGFR risk factors were assessed: diabetes mellitus (DM), history of urologic/nephrologic disease (HUND), nephrotoxic medication, cardiovascular disease, hypertension, age > 60 years, anaemia, malignancy and multiple myeloma/M. Waldenström. We studied four models: (1) all risk factors, (2) DM, HUND, hypertension, age > 60 years; (3) DM, HUND, cardiovascular disease, hypertension; (4) DM, HUND, age > 75 years and congestive heart failure. For each model, association with eGFR < 60 ml/min/1.73 m(2) or eGFR < 45 ml/min/1.73 m(2) was studied. A total of 998 patients, mean age 59.94 years were included; 112 with eGFR < 60 ml/min/1.73 m(2) and 30 with eGFR < 45 ml/min/1.73 m(2). Model 1 detected 816 patients: 108 with eGFR < 60 ml/min/1.73 m(2) and all 30 with eGFR < 45 ml/min/1.73 m(2). Model 2 detected 745 patients: 108 with eGFR < 60 ml/min/1.73 m(2) and all 30 with eGFR < 45 ml/min/1.73 m(2). Model 3 detected 622 patients: 100 with eGFR < 60 ml/min/1.73 m(2) and all 30 with eGFR < 45 ml/min/1.73 m(2). Model 4 detected 440 patients: 86 with eGFR < 60 ml/min/1.73 m(2) and all 30 with eGFR < 45 ml/min/1.73 m(2). Associations were significant (p < 0.001). Model 4 is most effective, resulting in the lowest proportion of superfluous eGFR measurements while detecting all patients with eGFR < 45 ml/min/1.73 m(2) and most with eGFR < 60 ml/min/1.73 m(2). A major risk factor for contrast-induced nephropathy (CIN) is kidney disease. Risk factors are used to identify patients with pre-existent kidney disease. Evidence for risk factors to identify patients with kidney disease is limited. The number of eGFR measurements to detect kidney disease can be reduced.

  19. Olmesartan reduces inflammatory biomarkers in patients with stable coronary artery disease undergoing percutaneous coronary intervention: results from the OLIVUS trial.

    PubMed

    Miyoshi, Toru; Hirohata, Atsushi; Usui, Shinichi; Yamamoto, Keizo; Murakami, Takashi; Komatsubara, Issei; Kusachi, Shozo; Ohe, Tohru; Nakamura, Kazufumi; Ito, Hiroshi

    2014-03-01

    The OLmesartan on the progression of coronary atherosclerosis: evaluation by IntraVascular UltraSound (OLIVUS) trial demonstrated that an angiotensin II receptor blocker, olmesartan, reduces the rate of coronary atheroma progression as evaluated by intravascular ultrasound in patients with stable angina pectoris undergoing percutaneous coronary intervention. This substudy examined the impact of olmesartan on serum biomarkers and the relationship between biomarker changes and atheroma progression. Patients in the OLIVUS trial (n = 247) were randomly assigned to a control group or the olmesartan group. A subgroup of these patients (n = 135, 55 %) was analyzed at baseline and at 14 months. Patients' characteristics and blood-pressure control were identical between the control group (n = 65) and the olmesartan group (n = 70), and also between the subpopulation and total population. The change in the level of high-sensitivity C-reactive protein (hs-CRP) (mg/l) and adiponectin (μg/ml) was significantly greater in the olmesartan group than in the control group (between-group differences: 0.5 and -0.7; 95 % confidence interval: 0.2-0.8 and -1.3 to -0.1; P = 0.001 and 0.02, respectively). Multiple regression analysis revealed that the nominal changes in total atheroma volume and percent atheroma volume were significantly associated with the nominal change in hs-CRP in the olmesartan group but not in the control group. Olmesartan reduced hs-CRP in patients with stable angina, and this correlated with the change in coronary atheroma.

  20. Prevalence and characterization of uremic pruritus in patients undergoing hemodialysis: uremic pruritus is still a major problem for patients with end-stage renal disease.

    PubMed

    Zucker, Inbar; Yosipovitch, Gil; David, Michael; Gafter, Uzi; Boner, Geoffrey

    2003-11-01

    Pruritus is a common disabling problem in patients with advanced end-stage renal disease. Few studies have evaluated the clinical characteristics of uremic itch. The aim of this multicenter study was to provide a comprehensive description of the prevalence and clinical characteristics of pruritus affecting patients with end-stage renal disease who are undergoing hemodialysis. A detailed questionnaire recently developed was used to evaluate pruritus in 219 patients undergoing hemodialysis treatment in 3 dialysis units. We examined the relationship of the quality of dialysis and various factors and medical parameters to itch. Pruritus was a common symptom in the study population. Approximately 66% of the patients had pruritus at some point, and 48% were affected by it at the time of the study. There was no correlation between the occurrence of pruritus and demographic or medical parameters (type of kidney disease, medical management, dialysis efficacy as expressed by Kt/V) of the patient. The data suggest that uremic pruritus tends to be prolonged, frequent, and intense, and it can impair the patient's quality of life including a negative effect on sleep and mood. Major factors found to exacerbate pruritus include rest, heat, dry skin, and sweat. Major factors found to reduce pruritus include activity, sleep, hot and cold shower, and cold. Treatment with angiotensin inhibitors seemed to be more common among those with uremia who had itch (P =.02) whereas furosemide was more commonly used among those who never itched (P =.002). This study provides a detailed description of uremic pruritus with new data on its characteristics including affective and sensory dimensions and associated symptoms.

  1. History of consolidation is prognostic in acute myeloid leukemia patients undergoing allogeneic hematopoietic cell transplantation in minimal residual disease-negative first complete remission.

    PubMed

    Rashidi, Armin; Linden, Michael A; DeFor, Todd E; Warlick, Erica; Bejanyan, Nelli; Yohe, Sophia; Weisdorf, Daniel J; Ustun, Celalettin

    2017-10-01

    Prognostic factors among acute myeloid leukemia (AML) patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) in minimal residual disease (MRD)-negative first complete remission (CR1) are unknown. We retrospectively attempted to answer the following question: In AML patients undergoing allo-HCT in MRD-negative CR1, does a history of prior consolidation provide additional prognostic information? The inclusion criteria were: (i) Age > 18 years, (ii) AML in CR1 after 1-2 cycles of intensive induction chemotherapy, with or without consolidation, (iii) Allo-HCT between 1/2003 and 4/2016 at our institution, (iv) Available standard-sensitivity 4-color flow cytometry results from a bone marrow aspiration at diagnosis and after completion of all previous chemotherapy within one month prior to HCT, (v) Flow cytometry-based MRD-negative status at the time of HCT. A history of prior consolidation was associated with favorable overall survival (Hazard Ratio [95% Confidence Interval]: 0.59 [0.35-0.99], P = .046), relapse-free survival (0.60 [0.37-0.96], P = .036), and relapse (0.50 [0.27-0.92], P = .025). Analysis of potential sources of bias was unrevealing. In AML patients undergoing allo-HCT in MRD-negative CR1, a history of prior consolidation was associated with favorable outcomes. If the path to pre-HCT MRD negativity includes consolidation, it may identify patients with improved prognosis following HCT in MRD-negative state. These results warrant validation in larger cohorts. © 2017 Wiley Periodicals, Inc.

  2. 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

  3. Contrast media use in patients with chronic kidney disease undergoing coronary angiography: A systematic review and meta-analysis of randomized trials.

    PubMed

    Pandya, Bhavi; Chaloub, Jean; Parikh, Valay; Gaddam, Sainath; Spagnola, Jonathan; El-Sayegh, Suzanne; Bogin, Marc; Kandov, Ruben; Lafferty, James; Bangalore, Sripal

    2017-02-01

    Patients with chronic kidney disease (CKD) undergoing coronary angiography (CA), adequate hydration and minimizing volume of contrast media (CM) are class 1b recommendations for preventing contrast induced nephropathy (CIN). Current data are insufficient to justify specific recommendations about isoosmolar vs. low-osmolar contrast media by the ACCF/AHA/SCAI guidelines. Randomized trials comparing IOCM to LOCM in CKD stage 3 and above patients undergoing CA, and reporting incidence of CIN (defined by a rise in creatinine of 25% from baseline) were included in the analysis. The secondary outcome of the study was the incidence of serum creatinine increase by >1mg/dl. A total of 2839 patients were included in 10 trials, in which 1430 patients received IOCM and 1393 received LOCM. When compared to LOCM, IOCM was not associated with significant benefit in preventing CIN (OR=0.72, [CI: 0.50-1.04], P=0.08, I2=59%). Subgroup analysis revealed non-significant difference in incidence of CIN based on baseline use of N-acetylcystine (NAC), diabetes status, ejection fraction, and whether percutaneous coronary intervention vs coronary angiography alone was performed. The difference between IOCM and LOCM was further attenuated when restricted to studies with larger sample size (>250 patients) (OR=0.93; [CI: 0.66-1.30]) or when compared with non-ionic LOCM (OR=0.79, [CI: 0.52-1.21]). In patients with CKD stage 3 and above undergoing coronary angiography, use of IOCM showed overall non-significant difference in incidence of CIN compared to LOCM. The difference was further attenuated when IOCM was compared with non-ionic LOCM. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Whey and soy protein supplements changes body composition in patients with Crohn's disease undergoing azathioprine and anti-TNF-alpha therapy.

    PubMed

    Machado, Júlia Figueiredo; Oya, Vanessa; Coy, Cláudio Saddy Rodrigues; Morcillo, André Moreno; Severino, Silvana Dalge; Wu, Chao; Sgarbieri, Valdemiro Carlos; Vilela, Maria Marluce dos Santos

    2015-04-01

    Crohn's disease (CD) is a chronic transmural inflammation of the gastrointestinal tract of unknown cause. Malnutrition associated with active CD has been reduced although obesity has increased. Dietary strategies such as those with high-protein have been proposed to reduce body fat. This study compares the effects of two supplements on the nutritional status of CD patients. 68 CD patients were randomized in two groups: whey protein group (WP) and soy protein group (SP). Using bioimpedance analysis, anthropometry and albumin and pre-albumin dosages the nutritional status was measured before starting the intervention and after 8 and 16 weeks. The disease activity was determined by Crohn's Disease Activity Index and serum C-reactive protein dosage and dietary intake by 24h dietary recalls. Forty-one patients concluded the study and both supplements changed body composition similarly. Triceps skin fold thickness (p< 0.001) and body fat percentage (p=0.001) decreased, whereas mid-arm muscle circumference (p=0.004), corrected arm muscle area (p=0.005) and body lean percentage (p=0.001) increased. For Crohn's disease patients undergoing anti TNF-alpha and azatioprine therapies, supplementation with whey and soy proteins changes body composition through reduction of body fat and thus contributes to control inflammation. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  5. [Development and evaluation of individualized fluid therapy in the elderly patients with coronary heart disease undergoing gastrointestinal surgery: a randomized, controlled trial].

    PubMed

    Zheng, Hong; Guo, Hai; Ye, Jian-rong; Chen, Lin

    2012-06-01

    To develop and evaluate an individualized fluid therapy in the elderly patients with coronary heart disease undergoing gastrointestinal surgery. In this prospective study, 60 coronary heart disease patients undergoing gastrointestinal surgery were included in the First Affiliated Hospital of Xinjiang Medical University from March 2009 to March 2012. Patients were randomized into the intervention group and the control group with 30 patients in each group. Individualized fluid therapy was used during surgery and postoperative period in the ICU, which was determined based on target controlled fluid therapy according to cardiac index, stroke volume, and stroke volume variation. Traditional fluid therapy was used in the control group in the intraoperative and postoperative period. The two groups were compared in terms of postoperative hemodynamic parameters, total fluid volume, incidence of adverse cardiac events, and recovery of bowel function. Compared with the control group, mean arterial pressure was significantly increased at the commencement of the surgery. The cardiac index was significantly elevated during surgery and at the end of the surgery. Stroke volume was significantly increased after induction of anesthesia, during the surgery, and at the early stay of ICU period(all P<0.05). Serum lactic acid in the intervention group was significantly lower at the end of surgery and during ICU stay than that in the control group (all P<0.05). During surgery and 24-hour stay in ICU, the total fluid volume, crystal usage, and urine were significantly less, while colloidal fluid use was significantly more in the intervention group as compared to the control group(all P<0.05). The perioperative adverse cardiac event rate was 36.7%(11/30) in the intervention group, lower than 56.7%(17/30) in the control group, but the difference was no statistically significance(P>0.05). In the intervention group, defecation time, time to first flatus, resumption of liquid intake, length of

  6. 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.

  7. Gut permeability is related to body weight, fatty liver disease, and insulin resistance in obese individuals undergoing weight reduction.

    PubMed

    Damms-Machado, Antje; Louis, Sandrine; Schnitzer, Anna; Volynets, Valentina; Rings, Andreas; Basrai, Maryam; Bischoff, Stephan C

    2017-01-01

    Obesity and associated metabolic disorders are related to impairments of the intestinal barrier. We examined lactulose:mannitol (Lac:Man) permeability in obese individuals with and without liver steatosis undergoing a weight-reduction program to test whether an effective weight-loss program improves gut barrier function and whether obese patients with or without liver steatosis differ in this function. Twenty-seven adult, nondiabetic individuals [mean ± SD body mass index (BMI; in kg/m(2)): 43.7 ± 5.2; 78% with moderate or severe liver steatosis] were included in the follow-up intervention study (n = 13 by month 12). All patients reduced their weight to a mean ± SD BMI of 36.4 ± 5.1 within 12 mo. We assessed barrier functions by the oral Lac:Man and the fecal zonulin tests. Insulin resistance was assessed by the homeostatic model assessment index (HOMA), and liver steatosis by sonography and the fatty liver index (FLI). The Lac:Man ratio and circulating interleukin (IL) 6 concentration decreased during intervention from 0.080 (95% CI: 0.073, 0.093) to 0.027 (95% CI: 0.024, 0.034; P < 0.001) and from 4.2 ± 1.4 to 2.8 ± 1.6 pg/mL (P < 0.01), respectively. At study start, the Lac:Man ratio was higher in patients with moderate or severe steatosis than in those without any steatosis (P < 0.001). The Lac:Man ratio tended to correlate with HOMA (ρ = 0.55, P = 0.052), which correlated with FLI (ρ = 0.75, P < 0.01). A multiple-regression analysis led to a final model explaining FLI best through BMI, waist circumference, and the Lac:Man ratio. Intestinal permeability is increased in obese patients with steatosis compared with obese patients without. The increased permeability fell to within the previously reported normal range after weight reduction. The data suggest that a leaky gut barrier is linked with liver steatosis and could be a new target for future steatosis therapies. This trial was registered at clinicaltrials.gov as NCT01344525. © 2017 American Society

  8. Correlation of Serum and Salivary Biochemical Parameters in end Stage Renal Disease Patients Undergoing Hemodialysis in Pre and Post-Dialysis State.

    PubMed

    Seethalakshmi, C; Koteeswaran, D; Chiranjeevi, V

    2014-12-01

    The aim of this study is to compare the salivary urea, creatine, sodium, potassium and phosphate in pre dialysis and post dialysis state in end stage renal disease patients and compare with the serum counterpart. The study group was selected from patients undergoing hemodialysis due renal failure of any cause, who are undergoing dialysis for at least one year duration in a private hospital in Chennai. The total number of subjects was 30. The venous blood was collected from the study group just prior to the dialysis and after the dialysis from the venous catheter which is placed for the purpose of hemodialysis. The collected samples were immediately (within 15 min) submitted to the laboratory for the biochemical examination of urea, creatinine, sodium, potassium and phosphate by an automated biochemical analyser. Unstimulated whole saliva was collected by spitting method from study group both before and after dialysis. The collected samples were immediately submitted to the laboratory for the biochemical examination of urea, creatinine, sodium, potassium and phosphate by an automated biochemical analyser. The paired t-test analysis was done in pre and post blood urea, creatinine, potassium and phosphate which was significant with a p-value of < 0.0001 and the same analysis was done in salivary urea in pre and post-dialysis state which also gave a significant reduction in the parameters with a p-value of < 0.0001.

  9. Assessment of Quality of Sleep and its Relationship with Psychiatric Morbidity and Socio-Demographic Factors in the Patients of Chronic Renal Disease Undergoing Hemodialysis.

    PubMed

    Zubair, Usama Bin; Butt, Batool

    2017-07-01

    To assess the subjective sleep quality and its relationship with the presence of psychiatric morbidity in the patients suffering from chronic kidney disease (CKD) and undergoing the procedure of hemodialysis (HD); and analyze the associated socio-demographic factors. Cross-sectional descriptive study. Nephrology Department, Military Hospital, Rawalpindi, from July to December 2016. Patients of CKD undergoing the HD were included in the final analysis. Quality of sleep was determined by using the Pittsburgh Sleep Quality Index (PSQI). Psychiatric morbidity was determined by the General Health Questionnaire 12 (GHQ-12). Relationship of education, BMI, gender, age, duration of dialysis, dialysis count per week, marital status, level of family income, psychiatric morbidity, occupation, biochemical markers (urea, creatinine, BUN, albumin, calcium, phosphorous and hemoglobin), tobacco smoking, and use of naswar was determined with the sleep quality. One hundred and forty patients were screened through the PSQI; 44 (31.4%) had good quality of sleep while 96 (68.6%) had poor sleep quality. Statistical analysis revealed that presence of psychiatric morbidity, increasing age, female gender, being unmarried, low family income, and low frequency of dialysis had significant association with the poor sleep quality. Poor sleep quality was highly prevalent among the patients of CKD receiving the hemodialysis. The patients with low family income, more age, and with two or less dialysis sessions per week should be screened thoroughly for the sleep problems. Presence of psychiatric morbidity emerged as an independent factor responsible for the poor sleep quality in our target population.

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

    PubMed

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

    2014-01-01

    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.

  11. Pitfalls in Interventional Pain Medicine: Hyponatremia after DDAVP for a Patient with Von Willebrand Disease Undergoing an Epidural Steroid Injection

    PubMed Central

    2017-01-01

    Desmopressin (DDAVP), a synthetic analog of vasopressin, has been used in patients with von Willebrand disease (VWD), mild hemophilia A, and platelet dysfunction to reduce the risk of bleeding associated with surgical and interventional procedures. We report the case of a patient with VWD presenting with a bulging disc and radicular pain that underwent transforaminal epidural steroid injections. Her course was complicated with the interval development of headaches and dizziness symptomatic of moderate hyponatremia, likely due to excessive fluid intake. This report highlights a relatively rare side effect of DDAVP when used for prophylaxis in patients with VWD and reinforces the need for vigilance in these patients. PMID:28392945

  12. 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

  13. Complications to cerebrospinal fluid drainage and predictors of spinal cord ischemia in patients with aortic disease undergoing advanced endovascular therapy.

    PubMed

    Mehmedagic, Irma; Resch, Timothy; Acosta, Stefan

    2013-08-01

    To study the complications after cerebrospinal fluid (CSF) drainage and predictors of spinal cord ischemia (SCI) after advanced endovascular therapy with CSF drainage for complex aortic disease. Between 2009 and 2012, 88 attempts of CSF drainage insertions/84 operations/83 patients, of the 658 operations for aortoiliac diseases, were performed. Indications for therapy were aortic dissection (n = 13) and aortic aneurysm (n = 70), of whom 38 had thoracoabdominal aortic aneurysm (TAAA). In all, 10 had ruptured aorta. The CSF drainages were inserted preoperatively (n = 75) and postoperatively (n = 9). In all, 14 CSF drainages were nonfunctioning. The SCI was present in 29 patients, transient/permanent in 12/17. Intraoperative circulatory instability (P = .001) and operation for TAAA, type II (P = .036), were associated with SCI. Meningitis (n = 1), epidural (n = 1), and subdural (n = 2) hematoma and needle-mediated paresis in 1 leg (n = 1) occurred after CSF drainage. Complication to CSF drainage occurred too frequently in this selected group of patients with high rate of SCI.

  14. MicroRNA 193b-3p as a predictive biomarker of chronic kidney disease in patients undergoing radical nephrectomy for renal cell carcinoma

    PubMed Central

    Trevisani, Francesco; Ghidini, Michele; Larcher, Alessandro; Lampis, Andrea; Lote, Hazel; Manunta, Paolo; Alibrandi, Maria Teresa Sciarrone; Zagato, Laura; Citterio, Lorena; Dell'Antonio, Giacomo; Carenzi, Cristina; Capasso, Giovambattista; Rugge, Massimo; Rigotti, Paolo; Bertini, Roberto; Cascione, Luciano; Briganti, Alberto; Salonia, Andrea; Benigni, Fabio; Braconi, Chiara; Fassan, Matteo; Hahne, Jens Claus; Montorsi, Francesco; Valeri, Nicola

    2016-01-01

    Background: A significant proportion of patients undergoing radical nephrectomy (RN) for clear-cell renal cell carcinoma (RCC) develop chronic kidney disease (CKD) within a few years following surgery. Chronic kidney disease has important health, social and economic impact and no predictive biomarkers are currently available. MicroRNAs (miRs) are small non-coding RNAs implicated in several pathological processes. Methods: Primary objective of our study was to define miRs whose deregulation is predictive of CKD in patients treated with RN. Ribonucleic acid from formalin-fixed paraffin embedded renal parenchyma (cortex and medulla isolated separately) situated >3 cm from the matching RCC was tested for miR expression using nCounter NanoString technology in 71 consecutive patients treated with RN for RCC. Validation was performed by RT–PCR and in situ hybridisation. End point was post-RN CKD measured 12 months post-operatively. Multivariable logistic regression and decision curve analysis were used to test the statistical and clinical impact of predictors of CKD. Results: The overexpression of miR-193b-3p was associated with high risk of developing CKD in patients undergoing RN for RCC and emerged as an independent predictor of CKD. The addition of miR-193b-3p to a predictive model based on clinical variables (including sex and estimated glomerular filtration rate) increased the sensitivity of the predictive model from 81 to 88%. In situ hybridisation showed that miR-193b-3p overexpression was associated with tubule-interstitial inflammation and fibrosis in patients with no clinical or biochemical evidence of pre-RN nephropathy. Conclusions: miR-193b-3p might represent a useful biomarker to tailor and implement surveillance strategies for patients at high risk of developing CKD following RN. PMID:27802451

  15. 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.

  16. Long-Term Outcome and Evaluation of Organ Function in Pediatric Patients Undergoing Haploidentical and Matched Related Hematopoietic Cell Transplantation for Sickle Cell Disease

    PubMed Central

    Dallas, Mari H.; Triplett, Brandon; Shook, David R.; Hartford, Christine; Srinivasan, Ashok; Laver, Joseph; Ware, Russell; Leung, Wing

    2013-01-01

    HLA-matched related donor (MRD) hematopoietic stem cell transplantation (HSCT) is a well-established therapy for patients with sickle cell disease (SCD); however, experience using alternative donors, including haploidentical donors, in HSCT for SCD is limited. We report the long-term outcomes of 22 pediatric patients who underwent related donor HSCT for SCD at St. Jude Children’s Research Hospital, either a myeloablative sibling MRD HSCT (n = 14) or reduced-intensity parental haploidentical donor HSCT (n = 8). The median patient age was 11.0 ± 3.9 years in the MRD graft recipients and 9.0 ± 5.0 years in the haploidentical donor graft recipients. The median follow-up was 9.0 ± 2.3 years, with an overall survival (OS) of 93% and a recurrence/graft failure rate of 0%, for the MRD cohort and 7.4 ± 2.4 years, with an OS of 75%, disease-free survival of 38%, and disease recurrence of 38%, for the haploidentical donor cohort. We report the long-term hematologic response and organ function in patients undergoing MRD or haploidentical donor HSCT for severe SCD. Our data demonstrate long-term hematologic improvements after HSCT with sustained engraftment, and confirm that HSCT offers long-term protection from common complications of SCD, including stroke, pulmonary hypertension, acute chest, and nephropathy, regardless of donor source. PMID:23416852

  17. Quality of life in women undergoing urinary diversion for bladder cancer: results of a multicenter study among long-term disease-free survivors

    PubMed Central

    2013-01-01

    Purpose Women undergoing radical cystectomy (RC) and urinary diversion for bladder cancer experience substantial limitations in health-related quality of life (HRQOL). However, the level of discomfort caused by different urinary diversion has been never evaluated in long term survivors. The aim of this multicenter study is to evaluate differences in HRQOL among recurrence-free women undergoing cutaneous ureterostomy (CUS), Bricker's ileal conduit (BK-IC) and Orthotopic neobladder VIP (ONB-VIP) in disease-free females treated with radical cystectomy (RC), with long-term follow up (mean 60.1 months; range 36-122 months). Materials and methods All consecutively treated female patients from two urological institutions who underwent RC and urinary diversion from January 2000 to December 2008, with no evidence of tumor recurrence at a minimum follow up of 36 months, were included. Patients received the European Organisation for Research and Treatment of Cancer (EORTC) generic (QLQ-C30) and bladder cancer-specific instruments (QLQ-BLM30) and the Functional Assessment of Cancer Therapy for Bladder Cancer (FACT-BL). Clinical data and questionnaire results were analyzed in order to evaluate the HRQOL differences among diversion groups. Results We identified 37 females (median age: 68, range 45–82 years), including 12 status-post CUS, 16 who underwent BK-IC, and 9 who underwent ONB-VIP. Most were healthy (24/37 with no comorbidities, 4/37 Charlson 1-2, 9/37 Charlson 3 or greater – we didn’t considered bladder cancer in Charlson evaluation because bladder cancer was the main inclusion criteria). Women undergoing CUS endorsed worse FACT-BL scores compared with BK-IC and ONB-VIP patients, worse HRQOL regarding physical and emotional well-being (p=0.008 and p=0.02, respectively), and a trend toward worse EORTC QLQ-C30 scores for appetite loss and fatigue (p=0.05 for both). Conclusions In our study long-term disease-free females treated with CUS endorsed worse HRQOL compared

  18. Prevalence and outcome of non-alcoholic fatty liver disease in adolescents and young adults undergoing weight loss surgery.

    PubMed

    Corey, K E; Stanley, T L; Misdraji, J; Scirica, C; Pratt, J; Hoppin, A; Misra, M

    2014-10-01

    We evaluated the prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) in 27 adolescents referred for weight loss surgery (WLS). On biopsy, 18 patients (66.7%) had NAFLD, and of those, 10 (37.0%) had NASH and 11 (40.7%) had fibrosis. Insulin, HbA1C and homeostatic model assessment of insulin resistance (HOMA-IR) were significantly higher in patients with NASH than those without NASH. Following WLS, 40% of patients with NASH had persistently elevated aminotransferase levels despite weight loss. We found that NASH is underdiagnosed in adolescents referred for WLS, and that hyperinsulinaemia, HOMA-IR and HbA1c can aid in identifying high-risk patients. © 2014 The Authors. Pediatric Obesity © 2014 International Association for the Study of Obesity.

  19. A comparison of two transfusion regimens in the perioperative management of children with sickle cell disease undergoing adenotonsillectomy.

    PubMed

    Wali, Yasser A; al Okbi, Hesham; al Abri, Rashed

    2003-01-01

    Adenotonsillar hypertrophy and chronic tonsillitis are common findings in patients with sickle cell disease (SCD). Various preoperative transfusion regimens have been suggested to reduce the population of sickle erythrocytes and correct the anemia, ranging from conservative (correcting the anemia) to aggressive (lowering the level of HbS to less than 30%). A total of 39 patients with SCD were included in the study. They were divided into 2 groups. Fourteen patients in group 1 were assigned aggressive exchange transfusion and 25 patients in group 2 were assigned a conservative (simple) transfusion. The 2 groups were compared for possible operative and postoperative complications. Thirty percent of patients in both groups had postoperative complications. They ranged from mild local infection to acute chest syndrome. Simple transfusion was not associated with higher incidence of complications and resulted in only one-third as many transfusion requirements.

  20. 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.

  1. Screening and management for ischemic heart disease in patients undergoing emergency surgery for a type A acute aortic dissection.

    PubMed

    Hata, Mitsumasa; Shiono, Motomi; Hata, Hiroaki; Sezai, Akira; Akiyama, Kenji; Orime, Yukihiko; Wakui, Shinji

    2014-09-01

    We assessed the incidence of coronary artery disease (CAD) during hospitalization after emergency surgery for a type A acute aortic dissection. A total of 123 patients underwent multi-slice computed tomography (MSCT) scans during an early stage after surgery. The patients were divided into two groups: group I consisted of 14 patients (11.4%) who had coronary artery stenosis of more than 75% on MSCT, and group II consisted of 109 patients (88.6%) who had no coronary lesions. The prevalence of diabetes, dyslipidemia and a smoking history was significantly higher in group I. Although the serum low-density lipoprotein cholesterol levels were similar, the high-density lipoprotein cholesterol (HDL) level was significantly lower in group I (36.4 ± 7.9 mg/dl) than in group II (49.6 ± 13.5 mg/dl, P = 0.0005). The maximum carotid intima-media thickness (IMT) was significantly thicker in group I (1.17 ± 0.37 mm) compared to group II (0.96 ± 0.33 mm, P = 0.0297). The logistic regression analysis detected that a carotid IMT over 1.1 mm (odds ratio 4.35, P = 0.0371) and HDL less than 40 mg/dl (odds ratio 3.90, P = 0.0482) were predictors for CAD. CAD screening should be recommended for patients with aortic dissection who have several atherosclerosis risk factors, even after emergency surgery.

  2. 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. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  3. Anal endosonography and bowel function in patients undergoing different types of endorectal pull-through procedures for Hirschsprung disease.

    PubMed

    Stensrud, Kjetil J; Emblem, Ragnhild; Bjørnland, Kristin

    2015-08-01

    The reasons for fecal incontinence after surgery for Hirschsprung disease (HD) remain unclear. The aim of this study was to examine the anal sphincters by anal endosonography and manometry after transanal endorectal pull-through, with or without laparotomy or laparoscopy, in HD patients. Furthermore, we aimed to correlate these findings to bowel function. Fifty-two HD patients were followed after endorectal pull-through. Anal endosonography and manometry were performed without sedation at the age of 3 to 16 years. Endosonographic internal anal sphincter (IAS) defects were found in 24/50 patients, more frequently after transanal than transabdominal procedures (69 vs. 19%, p=0.001). In a multiple variable logistic regression model, operative approach was the only significant predictor for IAS defects. Anal resting pressure (median 40mm Hg, range 15-120) was not correlated to presence of IAS defects. Daily fecal incontinence occurred more often in patients with IAS defects (54 vs. 25%, p=0.03). Postoperative IAS defects were frequently detected and were associated with daily fecal incontinence. IAS defects occurred more often after solely transanal procedures. We propose that these surgical approaches are compared in a randomized controlled trial before solely transanal endorectal pull-through is performed as a routine procedure. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. 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.

  5. Ultrasound-Guided Arterial Access: Outcomes Among Patients With Peripheral Artery Disease and Critical Limb Ischemia Undergoing Peripheral Interventions.

    PubMed

    Mustapha, J A; Diaz-Sandoval, Larry J; Jaff, Michael R; Adams, George; Beasley, Robert; Finton, Sara; McGoff, Theresa; Miller, Larry E; Ansari, Mohammad; Saab, Fadi

    2016-06-01

    Arterial cannulation is a vital component of endovascular interventions and often unconventional access approaches are required due to disease complexity. Historically, varying maneuvers have been utilized to obtain arterial access. Lack of consensus exists regarding the safest and most effective method. This study examined the feasibility and immediate outcomes of ultrasound-guided access in traditional and advanced access approaches. Data were analyzed from a cohort of 407 patients enrolled in the Peripheral RegIstry of Endovascular Clinical OutcoMEs (PRIME). The 407 patients underwent 649 procedures with 896 access sites utilized. Access success, immediate outcomes, complications, and length of hospital stay were analyzed. Mean age was 70 years, and 67% were male. The majority of patients had critical limb ischemia (58%), 39% were Rutherford classification III. Most commonly utilized access sites were common femoral retrograde, common femoral antegrade, posterior tibial, and anterior tibial arteries (34.6%, 33.0%, 12.1%, and 12.1%, respectively). Mean number of attempts was 1.2, 1.2, 1.5, and 1.4, respectively; median time to access was 39, 45, 41, and 59 seconds, respectively; and access success rate was 99.4%, 97.3%, 90.7%, and 92.6%; respectively. Access-site combinations utilized were femoral antegrade (n = 188), femoral retrograde (n = 185), dual femoral/ tibio-pedal (n = 130), dual femoral retrograde (n = 44), retrograde tibio-pedal (n = 73), and other (n = 29). Access-related complications were low overall: hematoma (1.2%), bleeding requiring transfusion/intervention (1.7%), pseudoaneurysm (1.7%), arteriovenous fistula (0.3%), aneurysm (0%), compartment syndrome (0%), and death (0%). Utilization of ultrasound-guided arterial access in this complex cohort was shown to be safe and effective regardless of arterial bed and approach.

  6. Pharmaco-economic consequences of losartan therapy in patients undergoing diabetic end stage renal disease in EU and USA.

    PubMed

    de Portu, Simona; Citarella, Anna; Cammarota, Simona; Menditto, Enrica; Mantovani, Lorenzo G

    2011-01-01

    Diabetic nephropathy is the most frequent cause of end stage renal disease (ESRD). As ESRD incidence increases continuously, more resources are needed for treatment. The objective was to evaluate the economic impact of losartan added to the standard care administered to diabetic subjects with ESRD. The analysis has involved more than 500 million inhabitants. Standard methods have been used in order to conduct an economic evaluation comparing the economic outcomes deriving from the administration of losartan added to standard care versus standard care alone in patients with type 2 diabetes mellitus (DM) and nephropathy over 3.4 years. The study was hence conducted from the perspective of the third-party payer. The clinical outcome data were based on the results from the Reduction of Endpoints in Non-Insulin Dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan (RENAAL) trial. Direct medical costs are referred to the purchase costs of losartan and to the costs of hospitalization. The costs were discounted back at an annual rate of 3%. Also sensitivity analysis was performed. The RENAAL study showed that losartan confers strong renal protection in patients with DM and nephropathy. Losartan results into cost saving in all countries considered: 3,602.98€/Italy, 4,531.35€/France, 3,019.66€/Germany, 3,949.50€/Switzer-land, and 3,855.50€/US per patient. Results are not sensitive to both clinical and economic variables. In addition to the medical benefits, this analysis demonstrates the economic relevance of the treatment with losartan in DM patients affected by nephropathy.

  7. Usefulness of Routine Periodic Fasting to Lower Risk of Coronary Artery Disease among Patients Undergoing Coronary Angiography

    PubMed Central

    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.

    2008-01-01

    Coronary artery disease (CAD) is common and multi-factorial. 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. While 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 (N1=4,629) enrolled in the Intermountain Heart Collaborative Study registry (1994-2002) were evaluated for association of religious preference with CAD diagnosis (≥70% coronary stenosis on angiography) or no CAD (normal coronaries, <10% stenosis). Consequently, another set of patients (N2=448) were surveyed (2004-2006) for association of behavioral factors with CAD, with the primary variable being routine fasting (i.e., abstinence from food and drink). 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, CI=0.35, 0.87; p=0.010) and this remained after adjustment for traditional risk factors (OR=0.46, CI=0.27, 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 similar effect size. In conclusion, not only proscription of tobacco, but also routine periodic fasting was associated with lower risk of CAD. PMID:18805103

  8. Clofarabine Combined with Busulfan Provides Excellent Disease Control in Adult Patients with Acute Lymphoblastic Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

    PubMed Central

    Kebriaei, P; Basset, Roland; Ledesma, C; Ciurea, S; Parmar, S; Shpall, EJ; Hosing, C; Khouri, Issa; Qazilbash, M; Popat, U; Alousi, A; Nieto, Y; Jones, RB; de Lima, M; Champlin, RE; Andersson, BS

    2014-01-01

    We investigated the safety and early disease-control data obtained with intravenous busulfan (Bu) combined with clofarabine (Clo) in patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (SCT). Fifty-one patients with median age 36 years (range 20–64) received a matched sibling (n=24), syngeneic (n=2) or matched unrelated donor transplant (n=25) for ALL in first complete remission (n=30), second complete remission (n=13), or with active disease (n=8). More than half of the patients had high-risk cytogenetic profiles as defined by the presence of t(9;22) (n=17), t(4;11) (n=3), or complex cytogenetics (n=7). Clo 40 mg/m2 was given once daily, each dose followed by pharmacokinetically-dosed Bu infused over three hours daily for 4 days followed by hematopoietic cell infusion 2 days later. The Bu dose was based upon the drug clearance determined by a test Bu dose, 32 mg/m2, given 48 hours prior to the high dose regimen. The target daily area under the curve (AUC) was 5,500 microMol-min for patients less than 60 years of age and 4000 microMol-min for patients ≥60 years of age. The regimen was well tolerated with 100 day non-relapse mortality (NRM) rate of 6%. With a median follow-up of 14 months among surviving patients (range, 6–28 months), the one-year overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) rates were 67% (95%CI: 55%–83%), 54% (95%CI: 41%–71%), and 32% (95%CI: 16%–45%), respectively. For patients transplanted in first remission, the one-year OS, DFS, and NRM rates were 74%, 64%, and 25%, respectively. The combination of Clo-Bu provides effective disease control while maintaining a favorable safety profile. PMID:22750645

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

    PubMed Central

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

    2011-01-01

    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

  10. Macrophage activation marker soluble CD163 and non-alcoholic fatty liver disease in morbidly obese patients undergoing bariatric surgery.

    PubMed

    Kazankov, Konstantin; Tordjman, Joan; Møller, Holger Jon; Vilstrup, Hendrik; Poitou, Christine; Bedossa, Pierre; Bouillot, Jean-Luc; Clement, Karine; Grønbaek, Henning

    2015-08-01

    Macrophages play an important role in non-alcoholic fatty liver disease (NAFLD). Soluble CD163 (sCD163) is a specific marker of macrophage activation. We aimed to measure sCD163 in morbidly obese patients with varying degrees of NAFLD before and after bariatric surgery (BS). Demographic, clinical, and biochemical data, and plasma sCD163 measured by enzyme-linked immunosorbent assay, of 196 patients were collected preoperatively and 3, 6, and 12 months after BS leading to significant weight loss. Peroperative liver biopsies were assessed for the NAFLD Activity Score (NAS), Kleiner fibrosis score, and the fatty liver inhibition of progression (FLIP) algorithm. In a subset, CD163 immunohistochemistry and real-time quantitative polymerase chain reaction for CD163 mRNA were performed. sCD163 was higher in patients with NAS ≥ 5 compared with those with NAS < 5 (2.4(2.0-3.1) vs 1.9(1.5-2.3) mg/L, P < 0.001) and in patients with bridging fibrosis (F ≥ 3) compared with lower fibrosis stages (2.6(2.0-4.9) vs 2.0(1.5-2.4) mg/L, P = 0.001). Preoperative sCD163 was independently associated with both the NAS (P = 0.002) and the fibrosis score (P = 0.024). sCD163 decreased after BS and was greatly reduced after 12 months, more rapidly so in patients with NAS ≥ 5 (P < 0.001) and non-alcoholic steatohepatitis (NASH) according to the FLIP algorithm (P = 0.03). Immunohistochemistry showed CD163-positive macrophages aligning fat-laden hepatocytes and forming microgranulomas in patients with NASH. CD163 mRNA expression did not vary with NAS. sCD163 increased in parallel with the severity of NAFLD in morbid obesity, indicating macrophage activation. BS reduced sCD163 even in patients with severe liver injury and fibrosis, suggesting full reversibility of macrophage activation associated with improved insulin sensitivity. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  11. 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

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

    PubMed

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

    2016-01-01

    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). 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%. 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. 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 40 years of age, followed by a detailed examination, may be

  13. Differences in Prevalence, Extent, Severity, and Prognosis of Coronary Artery Disease Among Patients With and Without Diabetes Undergoing Coronary Computed Tomography Angiography

    PubMed Central

    Rana, Jamal S.; Dunning, Allison; Achenbach, Stephan; Al-Mallah, Mouaz; Budoff, Matthew J.; Cademartiri, Filippo; Callister, Tracy Q.; Chang, Hyuk-Jae; Cheng, Victor Y.; Chinnaiyan, Kavitha; Chow, Benjamin J.W.; Cury, Ricardo; Delago, Augustin; Feuchtner, Gudrun; Hadamitzky, Martin; Hausleiter, Jörg; Kaufmann, Philipp; Karlsberg, Ronald P.; Kim, Yong-Jin; Leipsic, Jonathon; Labounty, Troy M.; Lin, Fay Y.; Maffei, Erica; Raff, Gilbert; Villines, Todd C.; Shaw, Leslee J.; Berman, Daniel S.; Min, James K.

    2012-01-01

    OBJECTIVE We examined the prevalence, extent, severity, and prognosis of coronary artery disease (CAD) in individuals with and without diabetes (DM) who are similar in CAD risk factors. RESEARCH DESIGN AND METHODS We identified 23,643 consecutive individuals without known CAD undergoing coronary computed tomography angiography. A total of 3,370 DM individuals were propensity matched in a 1-to-2 fashion to 6,740 unique non-DM individuals. CAD was defined as none, nonobstructive (1–49% stenosis), or obstructive (≥50% stenosis). All-cause mortality was assessed by risk-adjusted Cox proportional hazards models. RESULTS At a 2.2-year follow-up, 108 (3.2%) and 115 (1.7%) deaths occurred among DM and non-DM individuals, respectively. Compared with non-DM individuals, DM individuals possessed higher rates of obstructive CAD (37 vs. 27%) and lower rates of having normal arteries (28 vs. 36%) (P < 0.0001). CAD extent was higher for DM versus non-DM individuals for obstructive one-vessel disease (19 vs. 14%), two-vessel disease (9 vs. 7%), and three-vessel disease (9 vs. 5%) (P < 0.0001 for comparison), with higher per-segment stenosis in the proximal and mid-segments of every coronary artery (P < 0.001 for all). Compared with non-DM individuals with no CAD, risk of mortality for DM individuals was higher for those with no CAD (hazard ratio 3.63 [95% CI 1.67–7.91]; P = 0.001), nonobstructive CAD (5.25 [2.56–10.8]; P < 0.001), one-vessel disease (6.39 [2.98–13.7]; P < 0.0001), two-vessel disease (12.33 [5.622–27.1]; P < 0.0001), and three-vessel disease (13.25 [6.15–28.6]; P < 0.0001). CONCLUSIONS Compared with matched non-DM individuals, DM individuals possess higher prevalence, extent, and severity of CAD. At comparable levels of CAD, DM individuals experience higher risk of mortality compared with non-DM individuals. PMID:22699296

  14. Negative Screening Does Not Rule Out the Risk of Tuberculosis in Patients with Inflammatory Bowel Disease Undergoing Anti-TNF Treatment: A Descriptive Study on the GETAID Cohort.

    PubMed

    Abitbol, Yael; Laharie, David; Cosnes, Jacques; Allez, Matthieu; Nancey, Stéphane; Amiot, Aurélien; Aubourg, Alexandre; Fumery, Mathurin; Altwegg, Romain; Michetti, Pierre; Chanteloup, Elise; Seksik, Philippe; Baudry, Clotilde; Flamant, Mathurin; Bouguen, Guillaume; Stefanescu, Carmen; Bourrier, Anne; Bommelaer, Gilles; Dib, Nina; Bigard, Marc André; Viennot, Stephanie; Hébuterne, Xavier; Gornet, Jean-Marc; Marteau, Philippe; Bouhnik, Yoram; Abitbol, Vered; Nahon, Stéphane

    2016-10-01

    to describe the characteristics of incident cases of tuberculosis [TB] despite negative TB screening tests, in patients with inflammatory bowel disease [IBD] undergoing anti-TNF treatment, and to identify the risk factors involved. A retrospective descriptive study was conducted at GETAID centers on all IBD patients undergoing anti-TNF treatment who developed TB even though their initial screening test results were negative. The following data were collected using a standardized anonymous questionnaire: IBD, and TB characteristics and evolution, initial screening methods and results, and time before anti-TNF treatment was restarted. A total of 44 IBD patients [including 23 men; median age 37 years] were identified at 20 French and Swiss centers at which TB screening was performed [before starting anti-TNF treatment] based on Tuberculin Skin Tests [n = 25], Interferon Gamma Release Assays [n = 12], or both [n = 7]. The median interval from the start of anti-TNF treatment to TB diagnosis was 14.5 months (interquartile range [IQR] 25-75: 4.9-43.3). Pulmonary TB involvement was observed in 25 [57%] patients, and 40 [91%] had at least one extrapulmonary location. One TB patient died as the result of cardiac tamponade. Mycobacterium tuberculosis exposure was thought to be a possible cause of TB in 14 cases [32%]: 7 patients [including 6 health care workers] were exposed to occupational risks, and 7 had travelled to endemic countries. Biotherapy was restarted on 27 patients after a median period of 11.2 months [IQR 25-75: 4.4-15.2] after TB diagnosis without any recurrence of the infection. Tuberculosis can occur in IBD patients undergoing anti-TNF treatment, even if their initial screening results were negative. In the present population, TB was mostly extrapulmonary and disseminated. TB screening tests should be repeated on people exposed to occupational risks and/or travelers to endemic countries. Restarting anti-TNF treatment seems to be safe. Copyright © 2016

  15. A new machine learning approach for predicting the response to anemia treatment in a large cohort of End Stage Renal Disease patients undergoing dialysis.

    PubMed

    Barbieri, Carlo; Mari, Flavio; Stopper, Andrea; Gatti, Emanuele; Escandell-Montero, Pablo; Martínez-Martínez, José M; Martín-Guerrero, José D

    2015-06-01

    Chronic Kidney Disease (CKD) anemia is one of the main common comorbidities in patients undergoing End Stage Renal Disease (ESRD). Iron supplement and especially Erythropoiesis Stimulating Agents (ESA) have become the treatment of choice for that anemia. However, it is very complicated to find an adequate treatment for every patient in each particular situation since dosage guidelines are based on average behaviors, and thus, they do not take into account the particular response to those drugs by different patients, although that response may vary enormously from one patient to another and even for the same patient in different stages of the anemia. This work proposes an advance with respect to previous works that have faced this problem using different methodologies (Machine Learning (ML), among others), since the diversity of the CKD population has been explicitly taken into account in order to produce a general and reliable model for the prediction of ESA/Iron therapy response. Furthermore, the ML model makes use of both human physiology and drug pharmacology to produce a model that outperforms previous approaches, yielding Mean Absolute Errors (MAE) of the Hemoglobin (Hb) prediction around or lower than 0.6 g/dl in the three countries analyzed in the study, namely, Spain, Italy and Portugal. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Impact of Chronic Kidney Disease on Clinical Outcomes in Diabetic Patients Undergoing Percutaneous Coronary Intervention in the Era of Newer-Generation Drug-Eluting Stents

    PubMed Central

    Kim, Su-Min; Tripathy, Dipti Ranjan; Park, Sang Wook; Park, Bonil; Son, Jung-Woo; Lee, Jun-Won; Ahn, Sung-Gyun; Ahn, Min Soo; Kim, Jang-Young; Yoo, Byung-Su; Lee, Seung-Hwan; Yoon, Junghan

    2017-01-01

    Background and Objectives Chronic kidney disease (CKD) is known to be a major adverse predictor in diabetes mellitus (DM) patients undergoing percutaneous coronary intervention (PCI). It is expected that the use of newer-generation drug-eluting stents (DES) would improve clinical outcomes in these patients. We evaluated the impact of CKD on clinical outcomes in diabetic patients undergoing PCI using newer-generation DES in a real-world setting. Subjects and Methods A total of 887 patients who underwent PCI with newer-generation DES and who had a history of DM or HbA1c >6.5% at the time of hospitalization were analyzed. These patients were divided into groups without CKD (n=549) and with CKD (n=338). Among survivors at discharge, a patient-oriented composite outcome (POCO) including all-cause mortality, myocardial infarction (MI), and revascularization was evaluated, together with a device-oriented composite outcome (DOCO) including cardiac death, target vessel-related MI, and target lesion revascularization at a follow-up period of one year. Results The incidence of POCO (5.4% vs. 14.0%, log-rank p<0.001) and DOCO (1.1% vs. 4.1%, log-rank p<0.001) was higher in patients with CKD. According to multivariate analysis, which was adjusted for baseline differences in demographic, clinical, and angiographic factors, the presence of CKD was an independent predictor of POCO (hazard ratio [HR]: 1.82, 95% confidence interval [CI]: 1.07 to 3.12), but not of DOCO (HR 2.08, 95% CI: 0.69-6.28). Conclusion In DM patients, CKD is an independent and powerful predictor of patient-related outcomes, but not of device-related outcomes in the era of newer-generation DES. PMID:28382078

  17. Residual disease at the bronchial stump is positively associated with the risk of bronchoplerual fistula in patients undergoing lung cancer surgery: a meta-analysis.

    PubMed

    Li, Shuangjiang; Fan, Jun; Zhou, Jian; Ren, Yutao; Shen, Cheng; Che, Guowei

    2016-03-01

    Residual disease at the bronchial stump (RDBS) is regarded as an important factor possibly resulting in bronchopleural fistula (BPF) after lung cancer surgery, but this has not been confirmed. We conducted this meta-analysis to evaluate the effects of RDBS on BPF formation in patients undergoing lung cancer surgery. PubMed and EMBASE databases were searched for full-text articles that met our eligibility criteria. Odds ratios (ORs) with 95% confidence interval (95% CI) served as the summarized outcomes. Q-test and I(2) statistic were used to evaluate the level of heterogeneity, determining the fixed-effect model or random-effect model for quantitative synthesis. Sensitivity analysis was conducted to identify the possible origins of heterogeneity. The publication bias was assessed by Begg's test. A total of eight retrospective observational studies were included in our meta-analysis. In overall analysis, the pooled outcomes indicated that RDBS was significantly associated with BPF formation after lung cancer surgery (OR: 3.12; 95% CI: 1.72-5.64; P < 0.001). In subgroup analysis, the pooled outcomes revealed a significantly increased risk of post-pneumonectomy BPF in patients with RDBS (OR: 2.78; 95% CI: 1.06-7.28; P = 0.037). The subgroup analysis assessing the effects of RDBS on post-lobectomy BPF was given up due to the scarcity of available data. No heterogeneity was revealed within this meta-analysis. No evidence for publication bias was detected by Begg's test. Our meta-analysis indicates that RDBS is positively associated with the increased risk of BPF in patients undergoing lung cancer surgery. The further analysis also reveals an increased risk of post-pneumonectomy BPF in patients with RDBS. More accurate and comprehensive evidence should be collected and summarized in updated meta-analyses. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  18. Haemodynamic consequences of targeted single- and dual-site right ventricular pacing in adults with congenital heart disease undergoing surgical pulmonary valve replacement.

    PubMed

    Plymen, Carla M; Finlay, Malcolm; Tsang, Victor; O'leary, Justin; Picaut, Nathalie; Cullen, Shay; Walker, Fiona; Deanfield, John E; Hsia, T Y; Bolger, Aidan P; Lambiase, Pier D

    2015-02-01

    The purpose of this study was to create an epicardial electroanatomic map of the right ventricle (RV) and then apply post-operative-targeted single- and dual-site RV temporary pacing with measurement of haemodynamic parameters. Cardiac resynchronization therapy is an established treatment for symptomatic left ventricular (LV) dysfunction. In congenital heart disease, RV dysfunction is a common cause of morbidity-little is known regarding the potential benefits of CRT in this setting. Sixteen adults (age = 32 ± 8 years; 6 M, 10 F) with right bundle branch block (RBBB) and repaired tetralogy of Fallot (n = 8) or corrected congenital pulmonary stenosis (n = 8) undergoing surgical pulmonary valve replacement (PVR) for pulmonary regurgitation underwent epicardial RV mapping and haemodynamic assessment of random pacing configurations including the site of latest RV activation. The pre-operative pulmonary regurgitant fraction was 49 ± 10%; mean LV end-diastolic volume (EDV) 85 ± 19 mL/min/m(2) and RVEDV 183 ± 89 mL/min/m(2) on cardiac magnetic resonance imaging. The mean pre-operative QRS duration is 136 ± 26 ms. The commonest site of latest activation was the RV free wall and DDD pacing here alone or combined with RV apical pacing resulted in significant increases in cardiac output (CO) vs. AAI pacing (P < 0.01 all measures). DDDRV alternative site pacing significantly improved CO by 16% vs. AAI (P = 0.018), and 8.5% vs. DDDRV apical pacing (P = 0.02). Single-site RV pacing targeted to the region of latest activation in patients with RBBB undergoing PVR induces acute improvements in haemodynamics and supports the concept of 'RV CRT'. Targeted pacing in such patients has therapeutic potential both post-operatively and in the long term. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.

  19. 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

  20. 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.

  1. 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

  2. Mucosal disease-like syndrome in a calf persistently infected by Hobi-like pestivirus.

    PubMed

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

    2014-08-01

    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.

  3. 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.

  4. Increased procollagen type I C-terminal peptide levels indicate diastolic dysfunction in end-stage renal disease patients undergoing maintenance dialysis therapy.

    PubMed

    Su, Chi-Ting; Liu, Yen-Wen; Lin, Jou-Wei; Chen, Shih-I; Yang, Chun-Shin; Chen, Jyh-Hong; Hung, Kuan-Yu; Tsai, Wei-Chuan; Huang, Jenq-Wen

    2012-08-01

    Cardiac dysfunction is common among patients with end-stage renal disease. The aim of this study was to explore the determinants of diastolic dysfunction in patients with end-stage renal disease on maintenance hemodialysis. Patients with asymptomatic end-stage renal disease undergoing hemodialysis underwent Doppler tissue imaging analysis and two-dimensional speckle-tracking echocardiography with strain analysis. Blood studies included albumin, cardiac troponin T, and procollagen type I C-terminal peptide (PICP). All enrolled patients had left ventricular (LV) diastolic dysfunction and were stratified into two groups by a cutoff value of 13 for the ratio of early transmitral flow velocity to the average early diastolic annular velocity (E/e'). Seventy-two of the enrolled patients (87%) had grade 1 diastolic dysfunction, and 11 patients (13%) had higher grades of diastolic dysfunction. The study population did not include a representative sample of patients with the pseudonormal or restrictive filling patterns of diastolic dysfunction. There were no significant differences in gender, age, LV geometric change, ejection fraction, global systolic longitudinal strain and strain rate, and prevalence of comorbidities between groups. Patients with average E/e' ≥ 13 had higher PICP, which was significantly correlated with cardiac troponin T, average E/e', and systolic circumferential strain rate. By multivariate regression analysis, average E/e' level was an independent factor of PICP level (P = .047). Hemodialysis patients with high average E/e' ratios showed increased levels of LV filling pressure and higher severity levels of cardiac fibrosis, which occurred before the development of systolic dysfunction. PICP was a potential indicator of diastolic dysfunction and increased LV filling pressure. Copyright © 2012 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.

  5. 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

  6. Impact of Donor Recipient Gender and Race Mismatch on Graft Outcomes in Patients With End-Stage Liver Disease Undergoing Liver Transplantation.

    PubMed

    Zhang, Yefei

    2017-03-01

    The discrepancy between donor supply and organ demand increased the possibility of gender and race mismatch between the donors and recipients. However, the findings of their impact on graft and patient survival are outdated and mixed. To estimate the effects of gender and race mismatch on graft survival and patient survival among adult patients (18 years and older) with end-stage liver disease. A total of 38 768 patients undergoing liver transplant between 2002 and 2011 were identified from United Network for Organ Sharing database. Kaplan-Meier curves, log-rank tests, and Cox proportional hazard regressions with backward elimination adopting a marginal approach with a working independence assumption and stratification on recipient hepatitis C virus status were used. Posttransplantation graft survival and patient survival. Both gender mismatch (hazard ratio [HR]: 1.14, 95% confidence interval [CI]: 1.09-1.12) and race mismatch (HR 1.08, 95%C: 1.04-1.12) had significantly adverse effects on graft survival and patient survival after controlling for other factors, especially among hepatitis C-positive female recipients with male donors (HR 1.13, 95%CI 1.03-1.24), black recipients with white donors (1.39, 1.29-1.49) or Hispanic donors (HR 1.48, 95%CI 1.27-1.72), and these effects were even worse among hepatitis C-positive recipients. Gender and race mismatch between donors and recipients adversely affected graft survival and patient survival among adult patients with end-stage liver disease, both independently and after the adjustment for other factors. Future research is recommended to explore other factors such as new model for end-stage liver disease sharing policy change and disparities in access to waiting-list or transplantation.

  7. Therapy of endocrine disease: outcomes in patients with Cushing's disease undergoing transsphenoidal surgery: systematic review assessing criteria used to define remission and recurrence.

    PubMed

    Petersenn, Stephan; Beckers, Albert; Ferone, Diego; van der Lely, Aart; Bollerslev, Jens; Boscaro, Marco; Brue, Thierry; Bruzzi, Paolo; Casanueva, Felipe F; Chanson, Philippe; Colao, Annamaria; Reincke, Martin; Stalla, Günter; Tsagarakis, Stelios

    2015-06-01

    A number of factors can influence the reported outcomes of transsphenoidal surgery (TSS) for Cushing's disease - including different remission and recurrence criteria, for which there is no consensus. Therefore, a comparative analysis of the best treatment options and patient management strategies is difficult. In this review, we investigated the clinical outcomes of initial TSS in patients with Cushing's disease based on definitions of and assessments for remission and recurrence. We systematically searched PubMed and identified 44 studies with clear definitions of remission and recurrence. When data were available, additional analyses by time of remission, tumor size, duration of follow-up, surgical experience, year of study publication and adverse events related to surgery were performed. Data from a total of 6400 patients who received microscopic TSS were extracted and analyzed. A variety of definitions of remission and recurrence of Cushing's disease after initial microscopic TSS was used, giving broad ranges of remission (42.0-96.6%; median, 77.9%) and recurrence (0-47.4%; median, 11.5%). Better remission and recurrence outcomes were achieved for microadenomas vs macroadenomas; however, no correlations were found with other parameters, other than improved safety with longer surgical experience. The variety of methodologies used in clinical evaluation of TSS for Cushing's disease strongly support the call for standardization and optimization of studies to inform clinical practice and maximize patient outcomes. Clinically significant rates of failure of initial TSS highlight the need for effective second-line treatments. © 2015 European Society of Endocrinology.

  8. Religious coping methods predict depression and quality of life among end-stage renal disease patients undergoing hemodialysis: a cross-sectional study.

    PubMed

    Santos, Paulo Roberto; Capote Júnior, José Roberto Frota Gomes; Cavalcante Filho, José Renan Miranda; Ferreira, Ticianne Pinto; Dos Santos Filho, José Nilson Gadelha; da Silva Oliveira, Stênio

    2017-06-17

    Poor quality of life (QOL) and a high prevalence of depression have been identified among end-stage renal disease (ESRD) patients undergoing hemodialysis (HD). We aimed to evaluate the associations between religious/spiritual (R/S) coping methods and both QOL and depression among ESRD patients undergoing hemodialysis (HD). The sample included 161 ESRD patients over 18 years of age who had been undergoing HD for more than 3 months. R/S coping methods were assessed using the Religious Coping Questionnaire (RCOPE). The RCOPE generates scores (from 1 to 5) for positive and negative R/S coping methods. The higher the score, the more frequent the use of that coping method. Depression was evaluated using the 20-item version of the Center for Epidemiologic Studies Depression Scale (CES-D). Scores on the CES-D range from 0 to 60. A cutoff of 18 was used to define depression. QOL was evaluated using the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36); this survey was used to generate scores for the eight dimensions of QOL, which can vary from 0 (worst) to 100 (best). We identified a depression prevalence of 27.3%. Positive R/S coping scores were higher among non-depressed than depressed patients (2.98 vs. 2.77; p = 0.037). Positive R/S coping scores were negatively correlated with depression scores (r = -0.200; p = 0.012) and were an independent protective factor for depression (OR = 0.13; CI 95% = 0.02-0.91; p = 0.039). Regarding QOL, a positive correlation was identified between positive R/S coping scores and scores related to general health (r = 0.171; p = 0.030) and vitality (r = 0.183; p = 0.019), and an inverse correlation was identified between negative R/S coping scores and scores in the social functioning (r = -0.191; p = 0.015) and mental health (r = -0.214; p = 0.006) dimensions. In addition, positive R/S coping scores were an independent predictor of higher scores in the bodily pain (β = 14.401; p = 0.048) and

  9. HE4 Serum Levels in Patients with BRCA1 Gene Mutation Undergoing Prophylactic Surgery as well as in Other Benign and Malignant Gynecological Diseases

    PubMed Central

    Cymbaluk-Płoska, Aneta; Strojna, Aleksandra; Menkiszak, Janusz

    2017-01-01

    Objective. We assess the behavior of serum concentrations of HE4 marker in female carriers of BRCA1 and assess the diagnostic usefulness of HE4 in ovarian and endometrial cancer. Methods. A total of 619 women with BRCA1 gene mutation, ovarian, endometrial, metastatic, other gynecological cancers, or benign gynecological diseases were included. Intergroup comparative analyses were carried out, the BRCA1 gene carriers subgroup was subjected to detailed analysis, and ROC curves were determined for the assessment of diagnostic usefulness of HE4 in ovarian and endometrial cancer. Results. Statistically lower serum HE4 and CA 125 levels were observed in BRCA1 gene mutation premenopausal carriers. Occult ovarian/fallopian tube cancer was found 3.6%. Each of those patients was characterized by slightly elevated levels of either CA 125 (63.9 and 39.4 U/mL) or HE4 (79 pmol/L). The ROC-AUC curves were 0.892 and 0.894 for diagnostic usefulness of ovarian cancer and 0.865 for differentiation of endometrial cancer from endometrial polyps. Conclusions. Patients with BRCA1 gene mutations have relatively low serum HE4 levels. Even the slightest elevation in HE4 or CA 125 levels in female BRCA1 carriers undergoing prophylactic surgery should significantly increase oncological alertness. The HE4 marker is valuable in ovarian and uterine cancer diagnosis. PMID:28182133

  10. Prophylactic levosimendan for the prevention of low cardiac output syndrome and mortality in paediatric patients undergoing surgery for congenital heart disease.

    PubMed

    Hummel, Johanna; Rücker, Gerta; Stiller, Brigitte

    2017-03-06

    Low cardiac output syndrome remains a serious complication, and accounts for substantial morbidity and mortality in the postoperative course of paediatric patients undergoing surgery for congenital heart disease. Standard prophylactic and therapeutic strategies for low cardiac output syndrome are based mainly on catecholamines, which are effective drugs, but have considerable side effects. Levosimendan, a calcium sensitiser, enhances the myocardial function by generating more energy-efficient myocardial contractility than achieved via adrenergic stimulation with catecholamines. Thus potentially, levosimendan is a beneficial alternative to standard medication for the prevention of low cardiac output syndrome in paediatric patients after open heart surgery. To review the efficacy and safety of the postoperative prophylactic use of levosimendan for the prevention of low cardiac output syndrome and mortality in paediatric patients undergoing surgery for congenital heart disease. We identified trials via systematic searches of CENTRAL, MEDLINE, Embase, and Web of Science, as well as clinical trial registries, in June 2016. Reference lists from primary studies and review articles were checked for additional references. We only included randomised controlled trials (RCT) in our analysis that compared prophylactic levosimendan with standard medication or placebo, in infants and children up to 18 years of age, who were undergoing surgery for congenital heart disease. Two review authors independently extracted data and assessed risk of bias according to a pre-defined protocol. We obtained additional information from all but one of the study authors of the included studies. We used the five GRADE considerations (study limitations, consistency of effect, imprecision, indirectness, and publication bias) to assess the quality of evidence from the studies that contributed data to the meta-analyses for the prespecified outcomes. We created a 'Summary of findings' table to

  11. Prophylactic levosimendan for the prevention of low cardiac output syndrome and mortality in paediatric patients undergoing surgery for congenital heart disease.

    PubMed

    Hummel, Johanna; Rücker, Gerta; Stiller, Brigitte

    2017-08-02

    Low cardiac output syndrome remains a serious complication, and accounts for substantial morbidity and mortality in the postoperative course of paediatric patients undergoing surgery for congenital heart disease. Standard prophylactic and therapeutic strategies for low cardiac output syndrome are based mainly on catecholamines, which are effective drugs, but have considerable side effects. Levosimendan, a calcium sensitiser, enhances the myocardial function by generating more energy-efficient myocardial contractility than achieved via adrenergic stimulation with catecholamines. Thus potentially, levosimendan is a beneficial alternative to standard medication for the prevention of low cardiac output syndrome in paediatric patients after open heart surgery. To review the efficacy and safety of the postoperative prophylactic use of levosimendan for the prevention of low cardiac output syndrome and mortality in paediatric patients undergoing surgery for congenital heart disease. We identified trials via systematic searches of CENTRAL, MEDLINE, Embase, and Web of Science, as well as clinical trial registries, in June 2016. Reference lists from primary studies and review articles were checked for additional references. We only included randomised controlled trials (RCT) in our analysis that compared prophylactic levosimendan with standard medication or placebo, in infants and children up to 18 years of age, who were undergoing surgery for congenital heart disease. Two review authors independently extracted data and assessed risk of bias according to a pre-defined protocol. We obtained additional information from all but one of the study authors of the included studies. We used the five GRADE considerations (study limitations, consistency of effect, imprecision, indirectness, and publication bias) to assess the quality of evidence from the studies that contributed data to the meta-analyses for the prespecified outcomes. We created a 'Summary of findings' table to

  12. Significance of incorporation of model for end-stage liver disease score with TNM staging in patients with hepatocellular carcinoma undergoing hepatic resection.

    PubMed

    Ling, Ching-Hsien; Chau, Gar-Yang; Hsia, Chen-Yuan; King, Kuang-Liang

    2013-01-01

    Currently, the tumor-node-metastasis (TNM) system is used in hepatectomy patients for tumor staging of HCC patients. However this can only evaluate the histopathological factor. MELD score is an objective measure for liver function widely used as a severity index for priority on the waiting list for liver transplantation. Here we suggest a modified TNM staging system based on the MELD score and test its relation with post-operative outcome of HCC. We retrospectively collected 922 HCC patients undergoing hepatic resection, with TNM stage I (n=239), stage II (n=375) and stage III (n=308); giving points 0 to 2 for each stage (from I to III). Pre-operative MELD score was calculated and assigned 0 points for MELD <6; 1 for 6-8; 2 for >8. The two scores were added together to form a modified MELD-base TNM stage score and tested the correlation of this new scoring system with outcome after liver resection. The modified MELD-base TNM stage score resulted in score 0 (n=114), score 1 (n=247), score 2 (n=335), score 3 (n=164), and score 4 (n=62). The disease-free survival in each group showed significant difference (p<0.05), the lower the score, the better the outcome. The MELD-based TNM staging system reliably separates patients with HCC into homogeneous groups with respect to post-resectional prognosis. Further prospective validation studies are required to confirm the feasibility of this strategy.

  13. Prediction of disease-free survival by the PET/CT radiomic signature in non-small cell lung cancer patients undergoing surgery.

    PubMed

    Kirienko, Margarita; Cozzi, Luca; Antunovic, Lidija; Lozza, Lisa; Fogliata, Antonella; Voulaz, Emanuele; Rossi, Alexia; Chiti, Arturo; Sollini, Martina

    2017-09-24

    Radiomic features derived from the texture analysis of different imaging modalities e show promise in lesion characterisation, response prediction, and prognostication in lung cancer patients. The present study aimed to identify an images-based radiomic signature capable of predicting disease-free survival (DFS) in non-small cell lung cancer (NSCLC) patients undergoing surgery. A cohort of 295 patients was selected. Clinical parameters (age, sex, histological type, tumour grade, and stage) were recorded for all patients. The endpoint of this study was DFS. Both computed tomography (CT) and fluorodeoxyglucose positron emission tomography (PET) images generated from the PET/CT scanner were analysed. Textural features were calculated using the LifeX package. Statistical analysis was performed using the R platform. The datasets were separated into two cohorts by random selection to perform training and validation of the statistical models. Predictors were fed into a multivariate Cox proportional hazard regression model and the receiver operating characteristic (ROC) curve as well as the corresponding area under the curve (AUC) were computed for each model built. The Cox models that included radiomic features for the CT, the PET, and the PET+CT images resulted in an AUC of 0.75 (95%CI: 0.65-0.85), 0.68 (95%CI: 0.57-0.80), and 0.68 (95%CI: 0.58-0.74), respectively. The addition of clinical predictors to the Cox models resulted in an AUC of 0.61 (95%CI: 0.51-0.69), 0.64 (95%CI: 0.53-0.75), and 0.65 (95%CI: 0.50-0.72) for the CT, the PET, and the PET+CT images, respectively. A radiomic signature, for either CT, PET, or PET/CT images, has been identified and validated for the prediction of disease-free survival in patients with non-small cell lung cancer treated by surgery.

  14. A comparison of cardiac output by thoracic impedance and direct fick in children with congenital heart disease undergoing diagnostic cardiac catheterization.

    PubMed

    Taylor, Katherine; La Rotta, Gustavo; McCrindle, Brian W; Manlhiot, Cedric; Redington, Andrew; Holtby, Helen

    2011-10-01

    To evaluate the measurement of cardiac output (CO) using continuous electrical bioimpedance cardiography (Physioflow; Neumedx, Philadelphia, PA) (CO(PF)) with a simultaneous direct Fick measurement (CO(FICK)) in children with congenital heart disease. A prospective cohort study comparing 2 methods of measurement of CO. A quaternary university-affiliated pediatric hospital. Children undergoing cardiac catheterization for clinical care. The Physioflow measured continuous real time CO in 15-second epochs and simultaneous measurement of cardiac output by direct Fick (with mass spectrometry to assess VO(2)) were acquired. Sixty-five patients were recruited, and data from 56 (25 males) were adequate for analysis. The median age at study was 3.5 years (range, 0.4-16.6 years), and the median body surface area was 0.62 m(2) (range, 0.31-1.71). There were 25 of 56 (45%) with univentricular physiology. A total of 19,228 Physioflow data points were available for the analysis of which 14,569 (76%) were valid; 96% of the invalid measurements were identified as artifacts by the device. The average cardiac index of valid measurements was 3.09 ± 0.72 L/min/m(2). Compared with the Fick CO, the mean bias was -0.09 L/min, but the 95% limits of agreement were -3.20 to +3.01 L/min/m(2). Consequently, only 20 of 56 (36%) of measurements were within 20%, and 31 of 56 (55%) of measurements were within 30% of each other. Compared with measurements made by direct Fick, CO measured using the Physioflow device was unreliable in anesthetized children with congenital heart disease. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Baseline cytokine profiling identifies novel risk factors for invasive fungal disease among haematology patients undergoing intensive chemotherapy or haematopoietic stem cell transplantation.

    PubMed

    Ceesay, M Mansour; Kordasti, Shahram; Rufaie, Eamaan; Lea, Nicholas; Smith, Melvyn; Wade, Jim; Douiri, Abdel; Mufti, Ghulam J; Pagliuca, Antonio

    2016-09-01

    Invasive fungal disease (IFD) is a disease of immunocompromised hosts. Cytokines are important mediators of innate and adaptive immune system. The aim of this study was to identify cytokine profiles that correlate with increased risk of IFD. We prospectively enrolled 172 adult haematology patients undergoing intensive chemotherapy, immunosuppressive therapy, and haematopoietic stem cell transplantation. Pro-inflammatory cytokine profiling using 30-plex Luminex assay was performed at baseline and during treatment. Nine single nucleotide polymorphisms (TLR1, TLR2, TLR3, TLR4.1, TLR4.2, TLR6, CLEC7A, CARD9, and INFG) were investigated among transplant recipients and donors. The incidence of IFD in this cohort was 16.9% (29/172). Median baseline serum concentrations of IL-15, IL-2R, CCL2, and MIP-1α were significantly higher whilst IL-4 was lower in patients with proven/probable IFD compared to those with no evidence of IFD. Baseline high IL-2R and CCL2 were associated with increased risk of IFD in the multivariate analysis (adjusted hazard ratio 2.3 [95% CI 1.1-5.1; P = 0.037], and hazard ratio 2.7 [95% CI 1.2-6.1; P = 0.016], respectively). However, these differences were not significant in follow up measurements. Similarly, no significant independent prognostic value was associated with baseline cytokine profile. High baseline IL-2R and CCL2 concentrations were independent indicators of the risk of developing IFD and could be used to identify patients for enhanced prophylaxis and early antifungal therapy. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  16. The influence of selective pulmonary perfusion on the inflammatory response and clinical outcome of patients with chronic obstructive pulmonary disease undergoing cardiopulmonary bypass.

    PubMed

    Kiessling, Arndt-Holger; Guo, Feng Wei; Gökdemir, Yildiz; Thudt, Marlene; Reyher, Christian; Scherer, Mirela; Beiras-Fernandez, Andres; Moritz, Anton

    2014-06-01

    Patients undergoing cardiac surgery presenting with chronic obstructive pulmonary disease (COPD) have a higher 30-day mortality risk. In these patients, pulmonary dysfunction linked to an inflammatory response is frequent after cardiac operations using cardiopulmonary bypass (CPB), which causes pulmonary hypoperfusion. We hypothesize that selective pulmonary perfusion (sPP) of the lungs leads to a reduction of pulmonary inflammation and a better clinical outcome. Fifty-nine COPD patients (forced expiratory volume in 1 s/vital capacity <70%) undergoing cardiac surgery procedures (coronary artery bypass grafting 64%, valve 14%) were block-randomized to sPP (venous blood, temperature 2°C, 4 l) or standard CPB (28/28). The primary end-point of the study was to evaluate the effect of pulmonary perfusion on gas exchange by measuring alveolar-arterial oxygen gradient. The surrogate end-points were inflammatory response, intensive care unit (ICU) stay, time on respirator (TOR) and major adverse cardiac and cerebrovascular events. A cytokine assay for interleukin-1β, IL-6, IL-10, tumour necrosis factor-α (TNF-α) and polymorphonuclear elastase was performed with peripheral blood at different time-points [(t1) pre-CPB, (t2) end of CPB, (t3) 3 h, (t4) 24 h, (t5) 48 h postoperatively]. Repeated-measure analysis of variance and non-parametric statistics were used to assess the between-group and during time differences. The two groups proved comparable for perioperative variables. Serum cytokines were not different in the two groups throughout the study (P > 0.05 at single time-points), but as a function of time, the markers of the inflammatory response increased after CBP (P < 0.05 pre-CPB to 24 h). Clinical end-points were statistically comparable in both groups, but with a trend towards a shorter TOR (72 ± 159 h/106 ± 193 h) and ICU stay (3.9 ± 7.2 days/5.5 ± 9.2 days) in the sPP group despite a slightly longer time on extracorporeal circulation (120 vs 158 min). These

  17. 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

  18. The ACTIVE Trial: comparison of the effects on renal function of iomeprol-400 and iodixanol-320 in patients with chronic kidney disease undergoing abdominal computed tomography.

    PubMed

    Thomsen, Henrik S; Morcos, Sameh K; Erley, Christiane M; Grazioli, Luigi; Bonomo, Lorenzo; Ni, Zhaohui; Romano, Luigia

    2008-03-01

    We performed a multicenter, double-blind, randomized, parallel-group study to compare the renal effects of iomeprol-400 and iodixanol-320 in patients with preexisting chronic kidney disease undergoing contrast-enhanced multidetector computed tomography of the liver. One hundred forty-eight patients with moderate-to-severe chronic kidney disease, ie, serum creatinine (SCr) > or =1.5 mg/dL (132.6 micromol/L) and/or calculated creatinine clearance (CrCl) <60 mL/min, undergoing contrast-enhanced multidetector computed tomography of the liver were randomized to equi-iodine doses (40 gI) of either the low-osmolar agent iomeprol-400 (400 mgI/mL, 726 mOsm/kg, N = 76) or the isotonic agent iodixanol-320 (320 mgI/mL, 290 mOsm/kg, N = 72), injected intravenously at 4 mL/S, followed by a bolus of 20 mL normal saline solution at the same rate. SCr was obtained at screening, baseline and at 48 to 72 hours postdose. SCr measurements and CrCl calculations were performed by a central laboratory. Contrast-induced nephropathy (CIN) was defined as an absolute SCr increase of > or =0.5 mg/dL (44.2 micromol/L) from baseline to 48 to 72 hours postdose. Mean SCr changes from baseline were also assessed. A Renal Safety Review Board comprised 3 medical experts reviewed the renal safety data, demographics, medical history, CIN risk factors, concomitant medications, and hydration status of each subject in a blinded manner. The 2 study groups were comparable with regard to age, gender distribution, concomitant nephrotoxins, hydration status, and total iodine dose; however, the iomeprol-400 group showed a significantly higher proportion of patients with diabetes mellitus (P = 0.02). Baseline SCr was 1.7 +/- 0.6 mg/dL (150.3 +/- 53.0 micromol/L) in the iomeprol-400 group and 1.7 +/- 0.7 mg/dL (150.3 +/- 61.9 micromol/L) in the iodixanol-320 group (P = 0.87). Predose CrCl was 41.5 +/- 13.1 mL/Min in the iomeprol-400 group and 43.0 +/- 13.3 mL/Min in the iodixanol-320 group (P = 0.49). Five of 72

  19. The association of ABO blood type with disease recurrence and mortality among patients with urothelial carcinoma of the bladder undergoing radical cystectomy.

    PubMed

    Gershman, Boris; Moreira, Daniel M; Tollefson, Matthew K; Frank, Igor; Cheville, John C; Thapa, Prabin; Tarrell, Robert F; Thompson, Robert Houston; Boorjian, Stephen A

    2016-01-01

    To evaluate the association of ABO blood type with clinicopathologic outcomes and mortality among patients with urothelial carcinoma of the bladder treated with radical cystectomy (RC). We identified 2,086 consecutive patients who underwent RC between 1980 and 2008. Postoperative recurrence-free survival (RFS) and cancer-specific survival (CSS) were estimated using the Kaplan Meier method and compared with the log-rank test. Cox proportional hazards regression models were used to evaluate the association of ABO blood type with outcomes. A total of 913 (44%), 881 (42%), 216 (10%), and 76 (4%) patients had blood type O, A, B, and AB, respectively. Median postoperative follow-up among survivors was 11.0 years (interquartile range: 7.7-15.9y). Overall, 1,561 patients died, with 770 deaths attributable to bladder cancer. Non-O blood type was associated with significantly worse 5-year RFS (65% vs. 69%; P = 0.04) and/or CSS (64% vs. 70%; P = 0.02). In particular, among patients with≤pT2N0 disease, the 5-year RFS for those with non-O vs. O blood type was 75% vs. 82%, respectively (P = 0.002), whereas the 5-year CSS was 77% vs. 85%, respectively (P = 0.001). Moreover, on multivariable analysis, blood type A remained independently associated with an increased risk of cancer-specific mortality (hazard ratio = 1.22; P = 0.01). Non-O blood type, particularly blood type A, is associated with a significantly increased risk of death from bladder cancer among patients undergoing RC. If validated, the utility of a multimodal therapy approach, including perioperative chemotherapy, or more frequent postoperative surveillance in this cohort warrants further study. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Outcomes and Characteristics of Patients Undergoing Percutaneous Angioplasty Followed by Below-Knee or Above-Knee Amputation for Peripheral Artery Disease

    PubMed Central

    Wang, Chao-Yung; Wen, Ming-Shien; Hsieh, I-Chang; Hung, Ming-Jui; Wang, Chao-Hung; Chen, Chun-Chi; Chen, Tien-Hsing

    2014-01-01

    Objective Little is known about long-term outcomes among patients who receive percutaneous angioplasty (PTA) for peripheral artery disease (PAD) then undergo below-knee or above-knee amputations. We sought to determine clinical outcomes associated with below-knee or above-knee amputation, along with possible explanatory factors and treatment strategies. Methods Using data from Taiwan’s National Health Insurance Research Database from 1997 to 2010, 7,568 adult patients were divided into three groups: lower extremity preserved (LE), below-knee amputation (BK) and above-knee amputation (AK). We assessed outcomes including major adverse cardiovascular events (MACE) and associated risk factors. Results Overall MACE was significantly higher in the AK group compared to the LE and BK groups, over a mean follow-up of 2.45 years (hazard ratio [HR]: 1.81; 95% confidence interval [CI]: 1.50–2.18 for AK vs. LE; HR: 1.67; 95% CI: 1.36–2.06 for AK vs. BK). However MACE were similar for the BK and LE groups (HR: 1.08; 95% CI: 0.98–1.20). Overall mortality was highest in the AK group (HR: 1.65, 95% CI: 1.34–2.04 for AK vs. BK). As for patient characteristics, atrial fibrillation was more prevalent in the AK group than in the BK group (17% vs. 7%). Independent risk factors associated with death after above- or below-knee amputation included advanced age, heart failure, dialysis, male gender and high patient volume. Conclusion The MACE rate was highest in the AK group, whereas the LE and BK groups were similar in this regard. Furthermore, overall mortality increased with larger area of amputation. PMID:25354252

  1. The prognostic value of heart rate response during vasodilator stress myocardial perfusion imaging in patients with end-stage renal disease undergoing renal transplantation.

    PubMed

    AlJaroudi, Wael; Anokwute, Chiedozie; Fughhi, Ibtihaj; Campagnoli, Tania; Wassouf, Marwan; Vij, Aviral; Kharouta, Michael; Appis, Andrew; Ali, Amjad; Doukky, Rami

    2017-09-18

    In asymptomatic end-stage renal disease (ESRD) patients undergoing vasodilator stress myocardial perfusion imaging (MPI) prior to renal transplantation (RT), the impact of pre-transplant heart rate response (HRR) to vasodilator stress on post-RT outcomes is unknown. We analyzed a retrospective cohort of asymptomatic patients with ESRD who underwent a vasodilator stress SPECT-MPI and subsequently received RT. Blunted HRR was defined as HRR <28% for regadenoson stress and <20% for adenosine stress. The primary endpoint was major adverse cardiac events (MACE), defined as cardiac death or myocardial infarction. Clinical risk was assessed using the sum of risk factors set forth by the AHA/ACCF consensus statement on the assessment of RT candidates. Among 352 subjects, 140 had an abnormal pre-transplant HRR. During a mean follow-up of 3.2 ± 2.0 years, 85 (24%) MACEs were observed. Blunted HRR was associated with increased MACE risk (hazard ratio 1.72; 95% confidence interval 1.12-2.63, P = 0.013), and remained significant after adjustment for gender, sum of AHA/ACCF risk factors, summed stress score, baseline heart rate, and β-blocker use. HRR was predictive of MACE in patients with normal MPI and irrespective of clinical risk. Blunted HRR was associated with a significant increase in post-operative (30-day) MACE risk (17.9% vs 8.5%; P = 0.009). In asymptomatic ESRD patients being evaluated for RT, a blunted pre-transplant HRR was predictive of post-RT MACE. HRR may be a valuable tool in the risk assessment of RT candidates.

  2. Administrative database concerns: accuracy of International Classification of Diseases, Ninth Revision coding is poor for preoperative anemia in patients undergoing spinal fusion.

    PubMed

    Golinvaux, Nicholas S; Bohl, Daniel D; Basques, Bryce A; Grauer, Jonathan N

    2014-11-15

    Cross-sectional study. To objectively evaluate the ability of International Classification of Diseases, Ninth Revision (ICD-9) codes, which are used as the foundation for administratively coded national databases, to identify preoperative anemia in patients undergoing spinal fusion. National database research in spine surgery continues to rise. However, the validity of studies based on administratively coded data, such as the Nationwide Inpatient Sample, are dependent on the accuracy of ICD-9 coding. Such coding has previously been found to have poor sensitivity to conditions such as obesity and infection. A cross-sectional study was performed at an academic medical center. Hospital-reported anemia ICD-9 codes (those used for administratively coded databases) were directly compared with the chart-documented preoperative hematocrits (true laboratory values). A patient was deemed to have preoperative anemia if the preoperative hematocrit was less than the lower end of the normal range (36.0% for females and 41.0% for males). The study included 260 patients. Of these, 37 patients (14.2%) were anemic; however, only 10 patients (3.8%) received an "anemia" ICD-9 code. Of the 10 patients coded as anemic, 7 were anemic by definition, whereas 3 were not, and thus were miscoded. This equates to an ICD-9 code sensitivity of 0.19, with a specificity of 0.99, and positive and negative predictive values of 0.70 and 0.88, respectively. This study uses preoperative anemia to demonstrate the potential inaccuracies of ICD-9 coding. These results have implications for publications using databases that are compiled from ICD-9 coding data. Furthermore, the findings of the current investigation raise concerns regarding the accuracy of additional comorbidities. Although administrative databases are powerful resources that provide large sample sizes, it is crucial that we further consider the quality of the data source relative to its intended purpose.

  3. Preventive lymecycline therapy in women with a history of pelvic inflammatory disease undergoing first-trimester abortion: a clinical, controlled trial.

    PubMed

    Heisterberg, L; Gnarpe, H

    1988-07-01

    In a clinical, controlled trial 55 women with a history of pelvic inflammatory disease (PID) undergoing first-trimester abortion were randomized to either lymecycline therapy or placebo. Twenty-four women received lymecycline capsules 300 mg b.i.d. for 14 days starting on the morning of the abortion and 31 received similar placebo medication. In the lymecycline group 2 women (8.3%) and in the placebo group 7 (22.6%) contracted postabortal PID, a non-significant difference (p greater than 0.2). The variables age, gestational age, number of spontaneous abortions, births and episodes of PID, and Hegar size were not associated with the rate of postabortal PID. Women without previous induced abortions had a significantly increased rate of postabortal infection (p = 0.02), but the treatment did not influence this rate. Three women had a positive culture for Chlamydia trachomatis at the time of abortion and two of these had postabortal PID. None of 7 women with postabortal PID had significant increases in IgA, IgG or IgM chlamydia antibody titers, but two women with uncomplicated abortions had serological evidence of infection. The number of hospital days and amounts of antibiotics prescribed to women with postabortal PID were not significantly different between the two treatment groups (p greater than 0.05). Women with a history of PID had an elevated risk of postabortal PID warranting the use of some sort of prophylaxis, and screening for C. trachomatis in an abortion population is recommended.

  4. Epidemiology, management, and outcome of invasive fungal disease in patients undergoing hematopoietic stem cell transplantation in China: a multicenter prospective observational study.

    PubMed

    Sun, Yuqian; Meng, Fanyi; Han, Mingzhe; Zhang, Xi; Yu, Li; Huang, He; Wu, Depei; Ren, Hanyun; Wang, Chun; Shen, Zhixiang; Ji, Yu; Huang, Xiaojun

    2015-06-01

    The China Assessment of Antifungal Therapy in Hematological Disease study, the first large-scale observational study of invasive fungal disease (IFD) in China, enrolled 1401 patients undergoing hematopoietic stem cell transplantation (HSCT) (75.2% allogeneic and 24.8% autologous) at 31 hospitals across China. The overall incidence of proven or probable IFD was 7.7% (108 of 1401); another 266 cases (19.0%) were possible IFD. After allogeneic or autologous HSCT, the incidence of proven/probable IFD was 8.9% (94 of 1053) and 4.0% (14 of 348), respectively. Some cases (14 of 108) developed during conditioning before transplantation. The cumulative incidence of proven/probable IFD increased steeply in the first month after transplantation and after 6 months, the incidence was significantly higher in allogeneic than it was in autologous transplant recipients (9.2% versus 3.5%; P = .001) and when stem cells were derived from cord blood or bone marrow and peripheral blood (P = .02 versus other sources). Independent risk factors for proven/probable IFD in allogeneic HSCT were diabetes, HLA-matched unrelated donor, prolonged severe neutropenia (absolute neutrophil count > 500/mm(3) for >14 days), and immunosuppressants (odds ratio, 2.0 to 3.4 for all). Antifungal prophylaxis was independently protective (P = .01). Previous IFD and prolonged severe neutropenia were significant independent risk factors among autologous transplantation patients (P < .01, P = .04, respectively). In total, 1175 (83.9%) patients received antifungal prophylaxis (91.6% triazoles) and 514 (36.7%) were treated in the hospital with therapeutic antifungals (89.1% triazoles; median 27 days). Empirical, pre-emptive, and targeted antifungals were used in 82.3%, 13.6%, and 4.1% of cases, respectively. Overall mortality (13.4%; 188 deaths) was markedly higher in patients with proven (5 of 16; 31.3%), probable (20 of 92; 21.7%), or possible (61 of 266; 22.9%) IFD; allogeneic (171 of 1053; 16.2%) rather

  5. Long-term Results and Recurrence-Related Risk Factors for Crohn Disease in Patients Undergoing Side-to-Side Isoperistaltic Strictureplasty.

    PubMed

    Fazi, Marilena; Giudici, Francesco; Luceri, Cristina; Pronestì, Micaela; Tonelli, Francesco

    2016-05-01

    Side-to-side isoperistaltic strictureplasty (SSIS) is useful in patients undergoing surgery for Crohn disease (CD) to avoid wide small-bowel resections. To our knowledge, there are no definitive data regarding its recurrence risk factors. To evaluate the results obtained in a monocentric population of patients with CD who have undergone SSIS. From August 1996 to March 2010, 91 patients with CD underwent SSIS in our center. In this prospective observational study, side-to-side isoperistaltic strictureplasty was according the Michelassi technique in 69 patients and the Tonelli technique in 22 patients. Factors relating to the patient and the CD, surgery, and pharmacological therapy during the preoperative and perioperative periods were evaluated in association with medical or surgical recurrence. Side-to-side isoperistaltic strictureplasty. The recurrence-free curve was estimated using Kaplan-Meier analysis. Patients were stratified into cohorts in relation to the considered categorical variables and data were compared by using the Mantel-Cox log-rank test. Cox proportional hazard regression analysis was used to set up a predictive model simultaneously exploring the effects of all independent variables on a dichotomous outcome recurrence in relation to time. Among the 91 patients, the mean (SD) age was 39.5 (11.2) years and preoperative disease duration was 97.9 (85.8) months; 83 patients (91.2%) were followed up, of whom 37 (44.58%) experienced a recurrence at a mean (SD) of 55.46 (36.79) months after surgery (range, 9-140 months). The recurrence in the SSIS site at a mean (SD) of 48.25 (29.94) months after surgery affected 24 of 83 patients (28.9%), 9 being medical and 15 being surgical recurrence. Recurrence in the SSIS was statistically significantly associated with the time elapsed between diagnosis and surgery (P = .03). A borderline association between family history of CD and surgical recurrence (P = .054) was also found. Multivariate analysis

  6. Randomized trial of complete versus lesion-only revascularization in patients undergoing primary percutaneous coronary intervention for STEMI and multivessel disease: the CvLPRIT trial.

    PubMed

    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

    2015-03-17

    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. 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. 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. 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. 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 IRA. In such patients, inpatient total revascularization

  7. Elastase, α1-proteinase inhibitor, and interleukin-8 in children and young adults with end-stage kidney disease undergoing continuous ambulatory peritoneal dialysis.

    PubMed

    Polańska, Bożena; Augustyniak, Daria; Makulska, Irena; Niemczuk, Maria; Jankowski, Adam; Zwolińska, Danuta

    2014-06-01

    Peritoneal dialysis is one of the main modality of treatment in end-stage kidney diseases (ESKD) in children. In our previous work in chronic kidney disease patients, in pre-dialyzed period and on hemodialysis, the neutrophils were highly activated. The aim of this study was to assess an inflammatory condition and neutrophil activation in ESKD patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Thirteen CAPD patients without infection, both sexes, aged 2.5-24 years, and group of healthy subjects (C) were studied. For comparative purposes the conservatively treated (CT) group of ESKD patients was included. Neutrophil elastase in complex with α1-proteinase inhibitor (NE-α1PI; ELISA), α1-proteinase inhibitor (α1PI; radial immunodiffusion) and interleukin-8 (IL-8; ELISA) were measured in the blood samples from CAPD, CT, and C group and in the peritoneal dialysate fluid (PDF) samples of patients on CAPD. A significantly increased plasma NE-α1PI levels (median 176.5 μg/L, range 85.2-373.2 μg/L; p < 0.00005), serum IL-8 (median 18.6 pg/mL, range 15.73-35.28 pg/mL; p < 0.05), and slightly decreased serum α1PI (median 1,540 mg/L, range 1,270-1,955; p ≤ 0.05) compared to the control groups were found. There were no significant differences of analyzed parameters between CAPD and CT patients. The concentration ratio of NE-α1PI, α1PI and IL-8 in blood/PDF was 29.97, 8.24, and 4.48, respectively. There were significantly positive correlations between serum and PDF concentration of α1PI and IL-8 (r = 0.613, p < 0.05; r = 0.59; p < 0.005, respectively). The results of our study demonstrate that neutrophils are highly activated in non-infected CAPD patients. The pivotal marker of this activation is NE-α1PI. It may contribute to chronic inflammation and tissues injury.

  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. Evaluation of high-concentration sevoflurane for induction and nasotracheal intubation without muscle relaxant for infants with different pulmonary blood flow undergoing surgery for congenital heart diseases.

    PubMed

    Wang, Kai-Yuan; Wang, Hong-Wu; Xin, Lian-Feng; Wang, Yong-Wang; Xue, Yu-Liang

    2011-12-01

    Inhalational anesthesia with sevoflurane for endotracheal intubation without muscle relaxant is now used widely for pediatric patients. This study assessed the efficacy and safety of induction with high concentration sevoflurane and of nasotracheal intubation without muscle relaxant in infants with increased or decreased pulmonary blood flow (PBF) and undergoing surgery for congenital heart diseases. Fifty-five infants aged 2 - 12 months, weighing 4.7 - 10.0 kg, and scheduled for congenital cardiac surgery were enrolled. Subjects were divided into those with increased (IPBF group, n = 29) and decreased (DPBF group, n = 26) pulmonary blood flow. All infants received inhalational induction with 8% sevoflurane in 100.0% oxygen at a gas flow rate of 6 L/min. Nasotracheal intubation was performed 4 minutes after induction. Sevoflurane vaporization was decreased to 4.0% for placement of a peripheral intravenous line and invasive hemodynamic monitors. Five minutes later, sedatives and muscle relaxant were administered and the vaporizer was adjusted to 2% for maintenance of anesthesia. Bispectral index (BIS) scores, circulatory parameters, satisfactory and successful intubation ratios, adverse reactions, and complications of intubation were recorded. Times to loss of lash and pain reflexes were longer for the DPBF group (P < 0.01). Satisfactory intubation ratios were 93.1% and 61.5% for the IPBF and DPBF groups, respectively (P = 0.008). Successful intubation ratios were 96.6% and 76.9% for the IPBF and DPBF groups, respectively (P = 0.044). Following sevoflurane inhalation, blood pressures decreased significantly in the IPBF group but remained stable in the DPBF group. BIS scores declined to similar stable values, and a "nadir BIS" was recorded for both groups. No obvious adverse reactions or complications of intubation were noted perioperatively. Induction with high concentration sevoflurane, although faster for infants with IPBF, is safe for infants with IPBF or DPBF

  10. Detection of hepatitis C virus in patients with terminal renal disease undergoing dialysis in southern Brazil: prevalence, risk factors, genotypes, and viral load dynamics in hemodialysis patients.

    PubMed

    Vidales-Braz, Beatris Maria; da Silva, Naylê Maria Oliveira; Lobato, Rubens; Germano, Fabiana Nunes; da Mota, Luiza Dias; Barros, Elvino J G; de Martinez, Ana Maria Barral

    2015-02-03

    Hepatitis C (HCV) is a serious public health issue, and it is estimated that 3% of the world's population is infected. Patients in hemodialysis units have an increased risk for contracting HCV, and high prevalence rates have been found in hemodialysis units around the world. This study is aimed at determining the prevalence of HCV in patients with terminal chronic renal disease (tCRD) who have been submitted to hemodialysis and peritoneal dialysis in southern Brazil to characterize the most prevalent genotypes, the viral load, and possible risk factors and to assess the validity between the ELISA and RT-PCR detection methods. Of 320 patients from three dialysis units, 318 participated in this study. According to the medical records, 55 patients were reactive to HCV, as determined via ELISA. All 318 samples were submitted to RT-PCR and genotyped using an Abbott Realtime m2000 system. Data obtained through a questionnaire and chemical variables were associated with the HCV. The prevalence of HCV was 18.24% (58), and the concordance between the HCV serology and the RT-PCR was 94%. Three patients were diagnosed to be negative for HCV using the ELISA assay but positive when using RT-PCR. Genotype 1 was the most prevalent (46.7%) genotype, within which subtype 1a was the most frequent (74.1%). One of the risk factors associated with HCV infection was the length of time that the patient had been undergoing hemodialysis treatments (p < 0.001). Additionally, the viral load was found to vary when tested before and after hemodialysis (p < 0.001). The prevalence of HCV in dialysis units continues to remain high, indicating nosocomial contamination. RT-PCR detected the presence of the hepatitis C virus in patients with a non-reactive serology, which highlights the importance of performing molecular tests on dialysis patients. The variation in the viral load in patients submitted to hemodialysis indicates a possible destruction or gripping of viral particles to the

  11. 76 FR 17867 - Agency Forms Undergoing Paperwork Reduction Act Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-31

    ... HUMAN SERVICES Agency for Toxic Substances and Disease Registry Agency Forms Undergoing Paperwork Reduction Act Review The Agency for Toxic Substances and Disease Registry (ATSDR) publishes a list of... Disease Registry (ATSDR), Office of Noncommunicable Diseases, Injury, and Environmental Health...

  12. 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

  13. 75 FR 58394 - Agency Forms Undergoing Paperwork Reduction Act Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-24

    ... mothers have lower risks of breast and ovarian cancers and type 2 diabetes, and breastfeeding better protects infants against infections, chronic diseases like diabetes and obesity, and even childhood leukemia and sudden infant death syndrome (SIDS). However, the groups that are at higher risk for diabetes...

  14. 78 FR 60283 - Agency Forms Undergoing Paperwork Reduction Act Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-01

    ... 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 information... this notice. Proposed Project Monitoring and Reporting System for Chronic Disease Prevention...

  15. 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.

  16. 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, ...

  17. 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

  18. Chemotherapy, Total Body Irradiation, and Post-Transplant Cyclophosphamide in Reducing Rates of Graft Versus Host Disease in Patients With Hematologic Malignancies Undergoing Donor Stem Cell Transplant

    ClinicalTrials.gov

    2017-08-08

    Acute Myeloid Leukemia in Remission; Adult Acute Lymphoblastic Leukemia in Complete Remission; Chronic Myelogenous Leukemia, BCR-ABL1 Positive in Remission; Chronic Myelomonocytic Leukemia in Remission; Graft Versus Host Disease; Hodgkin Lymphoma; Minimal Residual Disease; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Non-Hodgkin Lymphoma; Plasma Cell Myeloma; Severe Aplastic Anemia; Waldenstrom Macroglobulinemia

  19. Role of vasopressin in the treatment of anaphylactic shock in a child undergoing surgery for congenital heart disease: a case report

    PubMed Central

    Di Chiara, Luca; Stazi, Giulia V; Ricci, Zaccaria; Polito, Angelo; Morelli, Stefano; Giorni, Chiara; La Salvia, Ondina; Vitale, Vincenzo; Rossi, Eugenio; Picardo, Sergio

    2008-01-01

    Introduction The incidence of anaphylactic reactions during anesthesia is between 1:5000 and 1:25000 and it is one of the few causes of mortality directly related to general anesthesia. The most important requirements in the treatment of this clinical condition are early diagnosis and maintenance of vital organ perfusion. Epinephrine administration is generally considered as the first line treatment of anaphylactic reactions. However, recently, new pharmacological approaches have been described in the treatment of different forms of vasoplegic shock. Case presentation We describe the case of a child who was undergoing surgery for ventricular septal defect, with an anaphylactic reaction to heparin that was refractory to epinephrine infusion and was effectively treated by low dose vasopressin infusion. Conclusion In case of anaphylactic shock, continuous infusion of low-dose vasopressin might be considered after inadequate response to epinephrine, fluid resuscitation and corticosteroid administration. PMID:18252001

  20. Relationship between model for end-stage liver disease score and 30-day outcomes for patients undergoing elective colorectal resections: an American college of surgeons-national surgical quality improvement program study.

    PubMed

    Lange, Erin O; Jensen, Christine C; Melton, Genevieve B; Madoff, Robert D; Kwaan, Mary R

    2015-05-01

    Patients with liver disease face significant risk of complications and death when considering elective colorectal resection for benign or malignant indications. We sought to determine the relationship between Model of End-Stage Liver Disease score and 30-day outcomes in patients undergoing elective colorectal resections. This was a retrospective cohort study. The study included hospitals participating in the National Surgical Quality Improvement Program. Adult patients who underwent elective colorectal resection from 2005 to 2011 were identified from the National Surgical Quality Improvement Program database. Patients missing laboratory values necessary to calculate the Model of End-Stage Liver Disease score were excluded (61% of 81,346 patients identified). Differences in patient- and disease-related characteristics by Model of End-Stage Liver Disease categories were assessed with χ analyses. Thirty-day mortality and major morbidity were examined using logistic regression. Of 31,950 patients undergoing elective colorectal resections (14% including proctectomy), most (60%) were performed for colon or rectal cancer; other benign indications included diverticulitis (20%), polyp (10%), and IBD (10%). A total of 58% of patients had a Model of End-Stage Liver Disease score of ≥7. Increasing scores were associated with older age; higher BMI; higher ASA class; lower albumin level; and higher incidence of diabetes mellitus, pulmonary and cardiac disease, hypertension, and dependent functional status. In univariate analysis, patients with higher scores had a greater risk of 30-day mortality (score = 6 (0.69%); 7-11 (1.62%); 11-15 (4.52%); >15, (5.01%); p < 0.0001). After controlling for other comorbidities, Model of End-Stage Liver Disease score remained a significant predictor of 30-day mortality, major complications, and respiratory complications. This was a retrospective analysis of administrative data, limiting some access to clinically relevant data. Consistent with

  1. 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

  2. Impact of Hepatic Steatosis on Disease-Free Survival in Patients with Non-B Non-C Hepatocellular Carcinoma Undergoing Hepatic Resection.

    PubMed

    Nishio, Takahiro; Hatano, Etsuro; Sakurai, Takaki; Taura, Kojiro; Okuno, Masayuki; Kasai, Yosuke; Seo, Satoru; Yasuchika, Kentaro; Mori, Akira; Kaido, Toshimi; Uemoto, Shinji

    2015-07-01

    Although the prevalence of non-B non-C hepatocellular carcinoma (NBNC HCC) has increased, its clinicopathologic characteristics remain unclear. We retrospectively analyzed 518 HCC patients who underwent hepatic resection. Hepatitis B surface antigen- and hepatitis C antibody-negative patients were categorized into the NBNC HCC group (n = 145); others were categorized into the hepatitis B or C HCC (BC HCC) group (n = 373). We subdivided the etiologies of NBNC HCC according to alcohol intake and presence of steatosis. NBNC HCC was associated with nonalcoholic fatty liver disease (NAFLD) (13.1 %), fatty liver disease with moderate alcohol intake (9.0 %), alcoholic liver disease (ALD) (29.7 %), cryptogenic disease (44.1 %), and other known etiologies (4.1 %). The prevalence of obesity, diabetes mellitus, and hypertension was higher and hepatic function was better in the NBNC HCC group, which had significantly larger tumors than the BC HCC group. The entire NBNC HCC group displayed similar overall and disease-free survival as the BC HCC group. Among the subdivisions, NAFLD-associated HCC patients had significantly better disease-free survival than ALD-associated HCC and BC HCC patients. Microvascular invasion (hazard ratio [HR] 2.30; 95 % confidence interval [CI] 1.33-3.96) and steatosis area <5 % of noncancerous region (HR 2.13; 95 % CI 1.21-3.93) were associated with disease-free survival in NBNC HCC patients. The prognosis of NBNC HCC was similar to that of BC HCC. Among NBNC HCC patients, NAFLD-associated HCC patients had a relatively low recurrence risk. Absence of steatosis in hepatic parenchyma had a significant impact on disease-free survival in NBNC HCC patients.

  3. Effect of 22q11.2 deletion on bleeding and transfusion utilization in children with congenital heart disease undergoing cardiac surgery

    PubMed Central

    Brenner, Michelle K.; Clarke, Shanelle; Mahnke, Donna K.; Simpson, Pippa; Bercovitz, Rachel S.; Tomita-Mitchell, Aoy; Mitchell, Michael E.; Newman, Debra K.

    2016-01-01

    Background Post-surgical bleeding causes significant morbidity and mortality in children undergoing surgery for congenital heart defects (CHD). 22q11.2 deletion syndrome (DS) is the second most common genetic risk factor for CHD. The deleted segment of chromosome 22q11.2 encompasses the gene encoding glycoprotein (GP) Ibβ, which is required for expression of the GPIb-V-IX complex on the platelet surface, where it functions as the receptor for von Willebrand factor (VWF). Binding of GPIb-V-IX to VWF is important for platelets to initiate hemostasis. It is not known whether hemizygosity for the gene encoding GPIbβ increases the risk for bleeding following cardiac surgery for patients with 22q11.2 DS. Methods We performed a case-control study of 91 pediatric patients who underwent cardiac surgery with cardiopulmonary bypass from 2004–2012 at Children’s Hospital of Wisconsin. Results Patients with 22q11.2 DS had larger platelets and lower platelet counts, bled more excessively and received more transfusion support with packed red blood cells in the early post-operative period relative to control patients. Conclusions Pre-surgical genetic testing for 22q11.2 DS may help to identify a subset of pediatric cardiac surgery patients who are at increased risk for excessive bleeding and who may require more transfusion support in the post-operative period. PMID:26492284

  4. Outcomes of pre-emptive and rescue use of percutaneous left ventricular assist device in patients with structural heart disease undergoing catheter ablation of ventricular tachycardia.

    PubMed

    Mathuria, Nilesh; Wu, Geru; Rojas-Delgado, Francia; Shuraih, Mossaab; Razavi, Mehdi; Civitello, Andrew; Simpson, Leo; Silva, Guilherme; Wang, Suwei; Elayda, MacArthur; Kantharia, Bharat; Singh, Steve; Frazier, O H; Cheng, Jie

    2017-01-01

    Patient selection and timing of percutaneous left ventricular assist device (pLVAD) insertion for maximal benefit during ventricular tachycardia (VT) ablation is not well defined. We aimed to assess the outcomes of pre-emptive and rescue use of pLVAD during VT ablation in patients with ischemic and non-ischemic cardiomyopathy. Between January 2009 and October 2011, 93 patients underwent VT ablation. Three groups were compared: (1) Rescue group (n = 12)-patients who required emergent pLVAD insertion due to hemodynamic collapse during VT ablation, (2) Pre-emptive group (n = 24)-patients who had pre-ablation pLVAD insertion, and (3) Non-pLVAD group (n = 57)-patients who did not undergo pLVAD insertion. Procedural outcomes including 30-day mortality were compared. Thirty-day mortality was higher in the Rescue group compared to the Pre-emptive group (58 vs. 4 %, p = 0.003) and non-pLVAD (58 vs. 3 %, p = 0.001) group. There was no significant difference in 30-day mortality or long-term freedom of VT between the pre-emptive and non-pLVAD groups. Despite rescue pLVAD insertion, hemodynamic collapse during VT ablation is associated with a persistently high 30-day mortality. Further studies are warranted to predict hemodynamic collapse and to refine the role of pLVAD in this setting.

  5. 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

  6. Effect of L-Carnitine Supplementation on Reverse Remodeling in Patients with Ischemic Heart Disease Undergoing Coronary Artery Bypass Grafting: A Randomized, Placebo-Controlled Trial.

    PubMed

    da Silva Guimarães, Sheila; de Souza Cruz, Wanise; da Silva, Licinio; Maciel, Gabrielle; Huguenin, Ana Beatriz; de Carvalho, Monicque; Costa, Bárbara; da Silva, Geisiane; da Costa, Carlos; D'Ippolito, João Alvaro; Colafranceschi, Alexandre; Scalco, Fernanda; Boaventura, Gilson

    2017-03-25

    During cardiac failure, cardiomyocytes have difficulty in using the substrates to produce energy. L-carnitine is a necessary nutrient for the transport of fatty acids that are required for generating energy. Coronary artery graft surgery reduces the plasma levels of L-carnitine and increases the oxidative stress. This study demonstrates the effect of L-carnitine supplementation on the reverse remodeling of patients undergoing coronary artery bypass graft. Patients with ischemic heart failure who underwent coronary graft surgery were randomized to group A - supplemented with L-carnitine or group B controls. Left ventricular ejection fraction, left ventricular systolic and diastolic diameters were assessed preoperatively, 60 and 180 days after surgery. Our study included 28 patients (26 [93.0%] males) with a mean age ± SD of 58.1 ± 10.5 years. The parameters for the evaluation of reverse remodeling did not improve after 60 and 180 days of coronary artery bypass grafting in comparison between groups (p > 0.05). Evaluation within the L-carnitine group showed a 37.1% increase in left ventricle ejection fraction (p = 0.002) and 14.3% (p = 0.006) and 3.3% (p > 0.05) reduction in systolic and diastolic diameters, respectively. L-carnitine supplementation at a dose of 50 mg/kg combined with artery bypass surgery did not demonstrate any additional benefit in reverse remodeling. However, evaluation within the L-carnitine group may indicate a clinical benefit of L-carnitine supplementation.

  7. [Bone disease in patients undergoing chronic hemodialysis treatment and the role in its development of magnesium in drinking water used in the preparation of dialysis solution].

    PubMed

    Ionova, D; Monov, A; Baldzhiĭski, A

    1985-01-01

    Studying the role of magnesium on uremic osseous disease in patients on chroniohemodialysis we examined 50 patients with chrovic renal diseases, chronic renal insufficiency (CRI) and chroniodialysis treatment (CDT) with duration of the dialysis treatment from I to 10 years, 3 years on the average, and compared it with control groups of 20 patients with chronic renal diseases without CRI, with duration of the diseases from 3 to 22 years, 9 years on the average and 20 patients with chronic renal diseases and CRI (stage I--III) on conservative treatment, with a duration of the CRI from 0.5 to 6 years, 2 years on the average. The following indices were studied in all patients: serum levels of calcium, phosphorus, magnesium and alkaline phosphatase--montry, to the dialysis patients the samples were taken at the beginning of dialysis séance, and calcium and magnesium content in drinking water used for the preparation of dialysis solution, was twice yearly investigated. In accordance with the bibliographic check up, the bones of all patients adequate for study were photographed with "soft" (mu)-roentgen rays, three times for the observation period, but severe bone changes (osteonecrosis and fractures)--were not established. The level of magnesium in serum of the patients by the end of dialysis séances in the significant group of them was impressive (p less than 0,001).(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Malaysian Cardiothoracic Surgery Registry--a patient registry to evaluate the health outcomes of patients undergoing surgery for cardiothoracic diseases in Malaysia.

    PubMed

    Anas, R; Rahman, I; Jahizah, H; Hassan, A; Ezani, T; Jong, Y H; Norzalina, E; Ziyadi, G; Balan, S; Ramadan, J; Lim, T O; Jamaiyah, H; Hidayah, H

    2008-09-01

    The formulation of the Cardiothoracic Registry. Cardiothoracic surgery is the field of medicine involved in surgical treatment of diseases affecting organs inside the thorax (the chest). It is a general treatment of conditions of the heart (heart disease) and lungs (lung disease). In Malaysia, due to lack of data collection we do not have estimates of number and outcome of such procedure in the country. Western figures are often used as our reference values and this may not accurately reflect our Malaysian population. The Malaysian Cardiothoracic Surgery Registry (MyCARE) by the Ministry of Health will be a valuable tool to provide timely and robust data of cardiology practice, its safety and cost effectiveness and most importantly the outcome of these patients in the Malaysian setting.

  9. Pilot study on parental stress and behavioral adjustment to the thalassemia major disease process in children undergoing iron-chelation in western Taiwan.

    PubMed

    Kuo, Huang-Tsung; Peng, Ching-Tien; Tsai, Ming-Yu

    2006-01-01

    Thalassemia was first described by Cooley and Lee in 1952 in several Italian children as a severe anemia with spleen and liver enlargement, skin discoloration, and bony changes. Great strides in management and intervention have not been matched by progress in psychosocial rehabilitation. Because parental stress and adaptation are of concern, this study focuses on parental stress and adjustment in response to the disease process of their afflicted children in western Taiwan. The parents of 18 thalassemia major patients (under 12 years of age) were interviewed (in two sessions) to determine their feelings, sources of stress, and support during their childrens' disease process. The study found that: 1) many parents suffer from stress as a result of the disease process, 2) all parents had similar concerns about iron chelation treatment, and 3) some resilience factors were present in the support system.

  10. 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.

  11. High Dose Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil in Preventing Graft Versus Host Disease in Patients With Hematological Malignancies Undergoing Myeloablative or Reduced Intensity Donor Stem Cell Transplant

    ClinicalTrials.gov

    2017-09-14

    Acute Leukemia; Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Diffuse Large B-Cell Lymphoma; Follicular Lymphoma; Graft Versus Host Disease; Hodgkin Lymphoma; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Recurrent Acute Myeloid Leukemia With Myelodysplasia-Related Changes; Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma; Secondary Myelodysplastic Syndrome

  12. Self-reported Clinical Meaningfulness Early in the Treatment Course Predicts Objective Outcomes in Men Undergoing Collagenase Clostridium histolyticum Injections for Peyronie Disease.

    PubMed

    Ziegelmann, Matthew J; Viers, Boyd R; Montgomery, Brian D; Westerman, Mary E; Savage, Joshua B; Trost, Landon W

    2017-08-01

    To compare perceived meaningfulness early in the course of collagenase Clostridium histolyticum (CCH) with final outcomes to evaluate its use as a predictor of efficacy. A registry of patients undergoing CCH from March 2014 to September 2016 was maintained. Patients were recommended to complete 4 injection cycles. After each cycle, patients completed a questionnaire that included, "If you stopped at this point, would you consider this a meaningful improvement for you?" Curve assessments were performed before and at therapy completion. Analyses were performed to compare objective curve changes and reported meaningfulness. Complete information was available on 52 patients, including 79% who reported meaningful results. Median improvement (interquartile range) was 25 degrees (15;35) in the meaningful (+) group compared with 5 degrees (0;15) in the meaningful (-) group (P = .0007). When stratified by perception early during therapy, patients who found the second series meaningful experienced a greater final curve improvement (P = .005). More than 50% of patients with curvature improvements of ≥10 degrees or ≥10% found the therapy meaningful. Among men with ≤5-degree improvement after 2 series, 83% (5/6) experienced further curve improvements (median 20 degrees). Interestingly, 50% of patients with improvement ≤10 degrees reported meaningfulness, including 40% without objective improvement. Objective curve outcomes can be stratified by early subjective clinical meaningfulness with CCH, and the majority of patients with ≥10-degree or ≥10% curve improvement found CCH meaningful. Men failing to achieve objective curve benefits after 2 series experience further curve improvements in the majority of cases. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Association of subclinical wall changes of carotid, femoral, and popliteal arteries with obstructive coronary artery disease in patients undergoing coronary angiography.

    PubMed

    Kafetzakis, Alexandros; Kochiadakis, George; Laliotis, Aggelos; Peteinarakis, Ioannis; Touloupakis, Emmanouel; Igoumenidis, Nikos; Katsamouris, Asterios

    2005-10-01

    To examine the association of occult atherosclerosis of carotid, femoral, and popliteal arteries with the presence and severity of obstructive coronary artery disease (CAD) in patients without a history or presence of cerebrovascular or peripheral arterial disease using ultrasound examination of peripheral arteries. One hundred eighty-four such individuals underwent routine coronary angiography. Obstructive CAD was found in 103 cases, which comprised the patient group. The remaining 81 individuals comprised the control group. All were blindly examined by duplex ultrasonography in order to assess occult atherosclerosis, as indicated by the estimation of intima-media thickness of the carotid artery (IMTC), intima-media thickness of the femoral artery (IMTF), intima-media thickness of the popliteal artery (IMTP), and ultrasonic biopsy (UB) of the carotid and femoral arteries. For the individuals with positive coronary angiography findings, the severity of CAD was estimated by the number of the diseased vessels. IMTC, IMTF, IMTP, and UB showed significant correlation with the presence of obstructive CAD, but only IMTC and IMTF were independent predictive factors, with specificity of 74% and 60% and sensitivity of 76% and 70%, respectively. Additionally, our analysis yielded a regression model that, for a given value of IMTC and IMTF, may estimate the probability of CAD: p (CAD) = e((- 4.765 + 3.36 IMTC + 1.91 IMTF))/1 + e((- 4.765 + 13.36 IMTC + 1.91 IMTF)). Patients with one-vessel disease had significantly lower IMTC (p < 0.001) and UB (p = 0.011) and lower IMTF (p = 0.057) than those with three-vessel disease. The assessment of occult atherosclerosis by duplex ultrasonography in both the carotid and the femoral arteries is significantly associated with the presence and severity of CAD.

  14. Cognitive and affective changes in mild to moderate Alzheimer's disease patients undergoing switch of cholinesterase inhibitors: a 6-month observational study.

    PubMed

    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.

  15. Failure of remote ischemic preconditioning to reduce the risk of postoperative acute kidney injury in children undergoing operation for complex congenital heart disease: a randomized single-center study.

    PubMed

    Pedersen, Kirsten Rønholt; Ravn, Hanne Berg; Povlsen, Johan Vestergaard; Schmidt, Michael Rahbek; Erlandsen, Erland Jørn; Hjortdal, Vibeke Elisabeth

    2012-03-01

    The objective of this study was to evaluate whether remote ischemic preconditioning can protect kidney function in children undergoing operation for complex congenital heart disease. Children (n = 113) aged 0 to 15 years admitted for complex congenital heart disease were randomly allocated according to age to remote ischemic preconditioning and control groups. After exclusion of 8 patients, we conducted the analysis on 105 patients (remote ischemic preconditioning group, n = 54; control group, n = 51). Before surgery, remote ischemic preconditioning was performed as 4 cycles of 5 minutes of ischemia by inflating a cuff around a leg to 40 mm Hg above the systolic pressure. End points were development of acute kidney injury, initiation of dialysis, plasma creatinine, estimated glomerular filtration rate, plasma cystatin C, plasma and urinary neutrophil gelatinase-associated lipocalin, and urinary output. Secondary end points included postoperative blood pressure, inotropic score, and mortality, as well as morbidity reflected by reoperation and stays in the intensive care unit and hospital. Overall, 57 of the children (54%) had acute kidney injury develop, with 27 (50%) in the remote ischemic preconditioning group and 30 (59%) in the control group (P > .2). Remote ischemic preconditioning was not associated with improvement in either any of the renal biomarkers or any of the secondary end points. We found no evidence that remote ischemic preconditioning provided protection of kidney function in children undergoing operation for complex congenital heart disease. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  16. The RANZCOG College Statement on prophylactic oophorectomy in older women undergoing hysterectomy for benign disease: is the evidence sufficient to change practice?

    PubMed

    Brand, Alison H

    2011-08-01

    In 2009, the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) published College Statement C-Gyn 25: "Prophylactic oophorectomy at the time of hysterectomy for benign gynaecological disease, which recommended that caution should be exercised in performing bilateral salpingo-oophorectomy (BSO) at the time of hysterectomy for benign disease in women younger than 65 years of age." The aims of the study were to assess current practice with regard to prophylactic oophorectomy in this setting and to assess knowledge about the College Statement. We also sought to review the evidence behind the Statement. An anonymous email survey of all consultant gynaecologists and gynaecology registrars in Sydney West Area Health Service (SWAHS) was conducted. The response rate was 52%. The survey found that there was an increasing tendency to remove ovaries with increasing patient age, and over 60% of gynaecologists would routinely recommend removal of ovaries during a hysterectomy for benign disease in a 60 year old woman. The survey also revealed a lack of knowledge as to the existence or content of the College Statement. A review of the literature found that evidence suggesting benefit in retention of ovaries in postmenopausal women has been extrapolated from a modelling study, observational studies or from data on premenopausal oophorectomy. A survey of gynaecologists revealed that few currently appear to adhere to the College Statement regarding prophylactic oophorectomy at the time of hysterectomy for benign disease. High quality evidence regarding either harm or benefit following retention of ovaries after menopause is lacking. Nevertheless, dialogue between clinicians and patients on this topic is important. © 2011 The Author. Australian and New Zealand Journal of Obstetrics and Gynaecology © 2011 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  17. Long-term oncological outcomes in patients with limited nodal disease undergoing radical prostatectomy and pelvic lymph node dissection without adjuvant treatment.

    PubMed

    Mandel, Philipp; Rosenbaum, Clemens; Pompe, Raisa S; Steuber, Thomas; Salomon, Georg; Chun, Felix K; Graefen, Markus; Huland, Hartwig; Tilki, Derya

    2017-08-21

    This study aimed at analysing long-term oncologic outcomes in prostate cancer patients with limited nodal disease (1-2 positive lymph nodes) without adjuvant therapy after radical prostatectomy (RP). We retrospectively analysed data of 209 pN1 patients who underwent RP between January 1998 and 2010 with one (160) or two (49) histologically proven positive lymph nodes (LNs) without adjuvant treatment. Biochemical recurrence-free survival, metastasis-free survival and cancer-specific survival (CSS) were reported. In multivariable regression analyses further prognosticators of oncologic outcome in these patients were analysed. Median follow-up was 60.2 months. There was no significant difference in oncologic outcome between patients with one and two positive LNs. 73.1% (76.7%) of patients with one (two) positive LNs had biochemical recurrence during the follow-up period, 20.0% (25.6%) developed metastasis and 8.1% (6.1%) died of their disease. The only factors significantly associated with oncologic outcome in multivariable analysis were Gleason score and pT-stage. Patients with limited nodal disease (1-2 positive LNs) without adjuvant therapy showed favourable CSS-rates above 94% after 5 years. A subgroup of these patients (37%) remained metastasis-free without need of salvage treatment.

  18. 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

  19. Automated Computer-Assisted Diagnosis of Obstructive Coronary Artery Disease in Emergency Department Patients Undergoing 256-Slice Coronary Computed Tomography Angiography for Acute Chest Pain.

    PubMed

    Hashoul, Sharbell; Gaspar, Tamar; Halon, David A; Lewis, Basil S; Shenkar, Yuval; Jaffe, Ronen; Peled, Nathan; Rubinshtein, Ronen

    2015-10-01

    A 256-slice coronary computed tomography angiography (CCTA) is an accurate method for detection and exclusion of obstructive coronary artery disease (OBS-CAD). However, accurate image interpretation requires expertise and may not be available at all hours. The purpose of this study was to evaluate the usefulness of a fully automated computer-assisted diagnosis (COMP-DIAG) tool for exclusion of OBS-CAD in patients in the emergency department (ED) presenting with chest pain. Three hundred sixty-nine patients in ED without known coronary disease underwent 256-slice CCTA as part of the assessment of chest pain of uncertain origin. COMP-DIAG (CorAnalyzer II) automatically reported presence or exclusion of OBS-CAD (>50% stenosis, ≥1 vessel). Performance characteristics of COMP-DIAG for exclusion and detection of OBS-CAD were determined using expert reading as the reference standard. Seventeen (5%) studies were unassessable by COMP-DIAG software, and 352 patients (1,056 vessels) were therefore available for analysis. COMP-DIAG identified 33% of assessable studies as having OBS-CAD, but the prevalence of OBS-CAD on CCTA was only 18% (66 of 352 patients) by standard expert reading. However, COMP-DIAG correctly identified 61 of the 66 patients (93%) with OBS-CAD with 21 vessels (2%) with OBS-CAD misclassified as negative. In conclusion, compared to expert reading, automated computer-assisted diagnosis using the CorAnalyzer showed high sensitivity but only moderate specificity for detection of obstructive coronary disease in patients in ED who underwent 256-slice CCTA. The high negative predictive value of this computer-assisted algorithm may be useful in the ED setting.

  20. Interaction of chronic total occlusion and chronic kidney disease in patients undergoing primary percutaneous coronary intervention for acute ST-elevation myocardial infarction.

    PubMed

    Bataille, Yoann; Plourde, Guillaume; Machaalany, Jimmy; Abdelaal, Eltigani; Déry, Jean-Pierre; Larose, Eric; Déry, Ugo; Noël, Bernard; Barbeau, Gérald; Roy, Louis; Costerousse, Olivier; Bertrand, Olivier F

    2013-07-15

    Chronic total occlusion (CTO) in a non-infarct-related artery and chronic kidney failure (CKD) are associated with worse outcomes after primary percutaneous coronary intervention (PCI). The aim of this study was to investigate the interaction of CTO and CKD in patients who underwent primary PCI for acute ST-segment elevation myocardial infarction (STEMI). Patients with STEMIs with or without CKD, defined as an estimated glomerular filtration rate <60 ml/min/1.73 m(2), were categorized into those with single-vessel disease and those with multivessel disease with or without CTO. The primary outcomes were the incidence of 30-day and 1-year mortality. Among 1,873 consecutive patients with STEMIs included between 2006 and 2011, 336 (18%) had CKD. The prevalence of CTO in a non-infarct-related artery was 13% in patients with CKD compared with 7% in those without CKD (p = 0.0003). There was a significant interaction between CKD and CTO on 30-day mortality (p = 0.018) and 1-year mortality (p = 0.013). Independent predictors of late mortality in patients with CKD were previous myocardial infarction (hazard ratio [HR] 1.71, 95% confidence interval [CI] 1.01 to 2.79), age >75 years (HR 1.86, 95% CI 1.19 to 2.95), a left ventricular ejection fraction after primary PCI <40% (HR 2.20, 95% CI 1.36 to 3.63), left main culprit artery (HR 4.46, 95% CI 1.64 to 10.25), and shock (HR 7.44, 95% CI 4.56 to 12.31), but multivessel disease with CTO was not a predictor. In contrast, multivessel disease with CTO was an independent predictor of mortality in patients without CKD (HR 3.30, 95% CI 1.70 to 6.17). In conclusion, in patients with STEMIs who underwent primary PCI, with preexisting CKD, the prevalence of CTO in a non-infarct-related artery was twice as great. In these patients, the clinical impact of CTO seems to be overshadowed by the presence of CKD. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Ascitic fluid drainage using a peritoneal dialysis catheter to prevent and treat multi-organ dysfunction in veno-occlusive disease in children undergoing hematopoietic stem cell transplantation.

    PubMed

    Parmar, Vijal; Lewis, Malcolm; Shenoy, Mohan; Bonney, Denise; Wynn, Robert

    2017-02-28

    Veno-occlusive disease (VOD), or sinusoidal obstruction syndrome, is a well-recognised, serious complication associated with the chemotherapy conditioning therapy used in hematopoietic stem cell transplantation (HSCT). Fluid management is typically challenging in children with this condition. We describe effective early use of peritoneal dialysis catheters to drain extravascular, intra-abdominal fluid in children with VOD, allowing intravascular fluid administration to preserve renal perfusion and function, preventing multi-organ dysfunction. All but one of the children are long-term survivors, both of their significant VOD and their HSCT. The child that did not survive died from their underlying metabolic illness, not VOD.

  2. 77 FR 76045 - Agency Forms Undergoing Paperwork Reduction Act Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-26

    ..., clinical and laboratory markers of HIV disease, manifestations of severe HIV disease, and deaths among... disease from HIV diagnosis, to AIDS, the end-stage disease caused by infection with HIV, and death. In... HUMAN SERVICES Centers for Disease Control and Prevention Agency Forms Undergoing Paperwork Reduction...

  3. Estimating the Proportion of Essential Tremor and Parkinson's Disease Patients Undergoing Deep Brain Stimulation Surgery: Five-Year Data From Columbia University Medical Center (2009-2014).

    PubMed

    Kestenbaum, Meir; Ford, Blair; Louis, Elan D

    2015-12-01

    The aim of this study was to estimate, at a tertiary referral center, the proportion of essential tremor (ET) and Parkinson's disease (PD) patients who underwent DBS surgery. DBS surgery is an important treatment for ET and PD. Surprisingly, there are no published data on the precise proportion of such patients who are referred for this procedure. Using the computerized billing database at the Center for Parkinson's Disease and Other Movement Disorders, Columbia University Medical Center, we searched for patients who received the diagnostic codes 333.1 (tremor) and 332.0 (PD) and who were followed by a doctor at the center during the 5-year period from 2009 to 2014. The number of patients who underwent DBS surgery for these diagnoses during this time period was also determined. Seventy-seven patients with these diagnoses (52 PD, 14 ET, and 11 ET + PD) who were followed at the center underwent DBS surgery during this time period. The proportion of ET patients who underwent DBS surgery was 2.90% (95% confidence interval [CI]: 1.78-4.02), and for PD this was 1.38% (95% CI: 1.04-1.72). The difference was significant (P < 0.001). At a tertiary-referral center, 1 in 34 ET patients and 1 in 72 PD patients underwent DBS surgery. Similar studies from other major centers would be of additional value. These data are likely to have utility when planning health care services for patients with these diagnoses.

  4. Effect of hospital case volume on treatment and in-hospital outcomes in patients undergoing percutaneous coronary intervention for acute myocardial infarction. Results from the Ibaraki Coronary Artery Disease Study (ICAS) Registry.

    PubMed

    Ohtsuka Machino, Tomoko; Toyama, Masahiro; Obara, Kenichi; Takeyasu, Noriyuki; Watanabe, Shigeyuki; Aonuma, Kazutaka

    2008-05-01

    The volume of percutaneous coronary interventions (PCI) performed in a hospital has been suggested to correlate with favorable outcomes in patients undergoing primary PCI for acute myocardial infarction (AMI). However, studies that use current data and compare treatment and outcomes for AMI among hospitals with different volumes are still limited in Japan. Between January 2004 and March 2006, 401 AMI patients underwent primary PCI in the 11 hospitals participating in the Ibaraki Coronary Artery Disease Study (ICAS). Clinical characteristics, treatment, and in-hospital outcomes were retrospectively compared between 254 patients admitted to high-volume PCI hospitals and 147 patients admitted to low-volume hospitals. Low-volume hospitals had a higher prevalence of multivessel disease patients. High-volume hospitals had longer onset-to-door times, which were offset by faster door-to-balloon times. Rates of coronary stent use and successful PCI were comparable between the groups. Low-volume hospitals more frequently performed intra-aortic balloon pumping. Length of stay was longer in low-volume hospitals, whereas in-hospital mortality, bypass surgery, and repeat PCI rates did not differ between groups. Although the present study assessed limited data based on small sample size, we observed that contemporary standard treatments including stent implantation were performed for AMI patients undergoing primary PCI in hospitals with both high and low case volumes. We did not find an obvious relationship between hospital PCI volume and in-hospital outcomes in our data. However, further prospective surveys should be attempted to confirm these results.

  5. Targeting oxidative stress attenuates trinitrobenzene sulphonic acid induced inflammatory bowel disease like symptoms in rats: Role of quercetin

    PubMed Central

    Dodda, Dilip; Chhajed, Ruchi; Mishra, Jitendriya; Padhy, Monalisa

    2014-01-01

    Objective: This study was aimed to investigate the beneficial effects of quercetin (QCT) against trinitrobenzene sulfonic acid (TNBS) induced clinical, morphological, and biochemical alterations in rats. Materials and Methods: Colitis in rats was induced by administration of TNBS (25 mg dissolved in 0.25 ml of 30% ethanol) 8 cm into the rectum of the rat using a catheter. The animals were divided into six experimental groups (n = 6); naive (saline only without TNBS administration), control (saline + TNBS), standard (sulfasalazine 25 mg/kg + TNBS), QCT (25) (QCT 25 mg/kg + TNBS), QCT (50) (QCT 50 mg/kg + TNBS), QCT (100) (QCT 100 mg/kg + TNBS). Sulfasalazine (25 mg/kg) and QCT (25, 50 and 100 mg/kg) were administered per oral for 11 days and the colonic damage was evaluated in terms of macroscopical (body weight, stool consistency, rectal bleeding, and ulcer index) and biochemical parameters (myeloperoxidase activity, lipid peroxidation, nitrite, and glutathione). Results: Treatment with QCT (50, 100 mg/kg) for 10 days following TNBS administration significantly attenuated the clinical, morphological, and biochemical alterations induced by TNBS, whereas it was found to be not effective at its lower dose (25 mg/kg) throughout the experimental protocol. Conclusion: QCT attenuates the clinical, morphological and biochemical alterations induced by TNBS possibly via its antioxidant mechanism. PMID:24987175

  6. External validation and clinical utility of a prediction model for 6-month mortality in patients undergoing hemodialysis for end-stage kidney disease.

    PubMed

    Forzley, Brian; Er, Lee; Chiu, Helen Hl; Djurdjev, Ognjenka; Martinusen, Dan; Carson, Rachel C; Hargrove, Gaylene; Levin, Adeera; Karim, Mohamud

    2017-07-01

    End-stage kidney disease is associated with poor prognosis. Health care professionals must be prepared to address end-of-life issues and identify those at high risk for dying. A 6-month mortality prediction model for patients on dialysis derived in the United States is used but has not been externally validated. We aimed to assess the external validity and clinical utility in an independent cohort in Canada. We examined the performance of the published 6-month mortality prediction model, using discrimination, calibration, and decision curve analyses. Data were derived from a cohort of 374 prevalent dialysis patients in two regions of British Columbia, Canada, which included serum albumin, age, peripheral vascular disease, dementia, and answers to the "the surprise question" ("Would I be surprised if this patient died within the next year?"). The observed mortality in the validation cohort was 11.5% at 6 months. The prediction model had reasonable discrimination (c-stat = 0.70) but poor calibration (calibration-in-the-large = -0.53 (95% confidence interval: -0.88, -0.18); calibration slope = 0.57 (95% confidence interval: 0.31, 0.83)) in our data. Decision curve analysis showed the model only has added value in guiding clinical decision in a small range of threshold probabilities: 8%-20%. Despite reasonable discrimination, the prediction model has poor calibration in this external study cohort; thus, it may have limited clinical utility in settings outside of where it was derived. Decision curve analysis clarifies limitations in clinical utility not apparent by receiver operating characteristic curve analysis. This study highlights the importance of external validation of prediction models prior to routine use in clinical practice.

  7. 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

  8. 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

    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

    2014-02-01

    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. 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 alanine aminotransferase (ALT) values. Six-hundred ninety-three suitable biopsies were evaluated. Biopsied patients had a median age of 45 years; 78.6% were female and 35.1% diabetic; median body mass index was 46 kg/m(2). Six-hundred thirty-five biopsied patients had preoperative ALTs. Median ALT was 25 IU/L (interquartile range [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. 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. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  9. The Risk of Tumour Recurrence in Patients Undergoing Renal Transplantation for End-stage Renal Disease after Previous Treatment for a Urological Cancer: A Systematic Review.

    PubMed

    Boissier, Romain; Hevia, Vital; Bruins, Harman Max; Budde, Klemens; Figueiredo, Arnaldo; Lledó-García, Enrique; Olsburgh, Jonathon; Regele, Heinz; Taylor, Claire Fraser; Zakri, Rhana Hassan; Yuan, Cathy Yuhong; Breda, Alberto

    2017-08-10

    Renal transplantation is the gold standard renal replacement therapy in end-stage renal disease owing to its superior survival and quality of life compared with dialysis. When the potential recipient has a history of cancer, the waiting period before renal transplantation is usually based on the Cincinnati Registry. To systematically review all available evidence on the risk of cancer recurrence in end-stage renal disease patients with a history of urological cancer. Medline, Embase, and the Cochrane Library were searched up to March 2017 for all relevant publications reporting oncologic outcomes of urological cancer in patients who subsequently received a transplantation or remained on dialysis. The primary outcome was time to tumour recurrence. Secondary outcomes included cancer-specific and overall survival. Data were narratively synthesised in light of methodological and clinical heterogeneity. The risk of bias of each included study was assessed. Thirty-two retrospective studies enrolling 2519 patients (1733 dialysed, 786 renal transplantation) were included. For renal cell carcinomas, the risks of recurrence, cancer-specific, and overall survival were similar between transplantation and dialysis. For prostate cancer, most of the tumours had favourable prognoses consistent with nomograms. Studies dealing with urothelial carcinomas (UCs) mainly included upper urinary tract UC in the context of aristolochic acid nephropathy, for which the risks of synchronous bilateral tumour and recurrence were high. Data on testicular cancer were scarce. Immunosuppression after renal transplantation does not affect the outcomes and natural history of low-risk renal cell carcinomas and prostate cancer. Therefore, the waiting time from successful treatment for these cancers to transplantation could be reduced. Except in the particular situation of aristolochic acid nephropathy, more studies are needed to standardise the waiting period after UC owing to the paucity of data. Renal

  10. Unexplained occurrence of multiple de novo pseudoaneurysms in patients with chronic kidney disease undergoing angioembolization for bleeding following percutaneous renal intervention: Are we dealing with infection or vasculitis?

    PubMed

    Sarkar, Debansu; Lal, Anupam; Agarwal, Mayank M; Mavuduru, Ravimohan S; Kumar, Santosh; Singh, Shrawan K

    2013-04-01

    Patients with chronic kidney disease (CKD) are more prone for bleeding following percutaneous renal intervention, as compared to those with normal renal function. Causes are multi-factorial. Finding multiple aneurysms away from the site of renal intervention following initial angioembolization for hemorrhage is very unusual in these patients. Clinical and radiological findings of all the patients who underwent renal angiography for post-intervention bleed for a period of 5 years were reviewed and analyzed. A total of 29 patients required angiography for post-intervention hemorrhage. Six patients had recurrence of hemorrhage for which they underwent repeat angiography. Four of these patients had appearance of multiple new aneurysms away from the site of percutaneous nephrostomy (PCN)/percutaneous nephrolithotomy (PNL) puncture and the site of previous bleeding. All the patients had CKD (creatinine >2.5 mg/dl). They were on prolonged preoperative urinary diversion and had polymicrobial urinary infection. Three patients had candiduria. None of these patients had re-bleeding after repeat embolization and treatment with antibacterial and antifungal agents. Development of multiple aneurysms away from the sites of punctures in patients with CKD following percutaneous intervention is very unusual. Its causation including infection with bacteria and fungus, reaction of embolizing material, and angiopathy needs to be explored.

  11. Primary prevention of atrial fibrillation with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients with end-stage renal disease undergoing dialysis.

    PubMed

    Lin, Ting-Tse; Yang, Yao-Hsu; Liao, Min-Tsun; Tsai, Chia-Ti; Hwang, Juey J; Chiang, Fu-Tien; Chen, Pau-Chung; Lin, Jiunn-Lee; Lin, Lian-Yu

    2015-08-01

    Current evidence suggests that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) reduce the incidence of new atrial fibrillation (AF) in a variety of clinical conditions, including the treatment of left ventricular dysfunction or hypertension. Here we assessed whether ACEIs and ARBs could decrease incidence of new-onset AF in patients with end-stage renal disease (ESRD). We identified patients from the Registry for Catastrophic Illness, a nation-wide database encompassing almost all of the patients receiving dialysis therapy in Taiwan from 1995 to 2008. Propensity score matching and Cox proportional hazards regression models were used to estimate hazard ratios for new-onset AF. Among 113,186 patients, 13% received ACEIs, 14% received ARBs therapy, and 9% received ACEIs or ARBs alternatively. After a median follow-up of 1524 days, the incidence of new-onset AF significantly decreased in patients treated with ACEIs (hazard ratio 0.587, 95% confidence interval 0.519-0.663), ARBs (0.542, 0.461-0.637), or ACEIs/ARBs (0.793, 0.657-0.958). The prevention of new-onset AF was significantly better in patients taking longer duration of ACEI or ARB therapy. The effect remained robust in subgroup analyses. Thus both ACEIs and ARBs appear to be effective in the primary prevention of AF in patients with ESRD. Hence, renin-angiotensin system inhibition may be an emerging treatment target for the primary prevention of AF.

  12. Phase I trial of intravenous cyclosporine to induce graft-versus-host disease in women undergoing autologous bone marrow transplantation for breast cancer.

    PubMed

    Kennedy, M J; Vogelsang, G B; Beveridge, R A; Farmer, E R; Altomonte, V; Huelskamp, A M; Davidson, N E

    1993-03-01

    We investigated if graft-versus-host disease (GVHD), which is associated with an antitumor effect, could be induced in women with advanced breast cancer by treatment with cyclosporine (CSA) following reinfusion of purged autologous marrow after treatment with high-dose chemotherapy and defined the toxicities of this approach. Fifty-one women with advanced breast cancer responding to therapy were treated with escalating doses of CSA (1.0, 2.5, or 3.75 mg/kg/d) for 28 days following high-dose chemotherapy and autologous bone marrow transplantation and monitored for induction of GVHD and toxicity of therapy. GVHD was induced in a dose-dependent fashion in 14%, 68%, and 92% of patients at each dose level, respectively, a median of 15 days following autologous marrow reinfusion. GVHD was clinically mild and limited to skin. Toxicity was acceptable, with two deaths within 50 days of marrow reinfusion. Statistically significant increases in maximum creatinine and bilirubin levels were seen at all dose levels when compared with similarly treated historic controls who did not receive CSA. Time to last platelet transfusion was significantly delayed in patients treated at the highest dose. GVHD can be safely induced by treatment with CSA in women with advanced breast cancer who are receiving high-dose alkylating agents and autologous bone marrow transplantation. The toxicity of this approach is acceptable. Evidence of antitumor efficacy awaits further investigation.

  13. Phase I trial of interferon gamma to potentiate cyclosporine-induced graft-versus-host disease in women undergoing autologous bone marrow transplantation for breast cancer.

    PubMed

    Kennedy, M J; Vogelsang, G B; Jones, R J; Farmer, E R; Hess, A D; Altomonte, V; Huelskamp, A M; Davidson, N E

    1994-02-01

    We investigated if interferon gamma (IFN-gamma) could augment cyclosporine (CSA)-induced graft-versus-host disease (GVHD) following autologous bone marrow transplant in women with metastatic breast cancer and defined the toxicities of this therapy. Thirty-six women with advanced breast cancer were treated with CSA 2.5 mg/kg daily for 28 days and IFN-gamma 0.025 mg/m2 subcutaneously (SC) every other day, days 7 to 28 following autologous bone marrow transplantation and monitored for induction and severity of GVHD and toxicity of therapy. GVHD was induced in 56% of patients. The severity of GVHD was greater than in a historic control population treated with CSA alone. Stage III rash was seen in 36% of patients, compared with 3% in the historic control population. Fourteen of 36 patients required therapy with topical corticosteroids and two of 36 required systemic treatment. Only three of 31 historic controls needed topical corticosteroids and no patient was treated systemically. There was no severe visceral GVHD. Hematopoietic recovery was not delayed. There were three toxic deaths. CSA-induced GVHD can be safely augmented by IFN-gamma in women treated with high-dose alkylating agents and autologous bone marrow transplantation. There is little evidence of increased toxicity. Evidence of antitumor efficacy awaits further investigation.

  14. The Parkinson's disease-related genes act in mitochondrial homeostasis.

    PubMed

    Sai, Yan; Zou, Zhongmin; Peng, Kaige; Dong, Zhaojun

    2012-10-01

    Neurons are metabolically active cells with high energy demands. Thus, neurons are particularly reliant on mitochondrial function, especially on the homeostasis properties of mitochondria. This is reflected by the observation that mitochondrial abnormalities have been well recognized to contribute to neurodegenerative diseases, like Parkinson's disease (PD). Mitochondria are highly complex and dynamic organelles continuously undergoing different alterations. The dynamic property of mitochondria is named as mitochondrial homeostasis. Imbalance of mitochondrial homeostasis is associated with neurodegenerative disease, such as Parkinson's diseases. Recently, the related genes of PD-familial, such as alpha-synuclein, Parkin, PINK1, DJ-1 and LRRK2, are observed to be associated with mitochondria, and capable of modulating normal mitochondrial integrity and functions under certain conditions. Therefore, in this review, we will focus on the action of PD-related genes in mitochondrial homeostasis. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  15. 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. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All

  16. 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

  17. The cardiothoracic ratio and all-cause and cardiovascular disease mortality in patients undergoing maintenance hemodialysis: results of the MBD-5D study.

    PubMed

    Ogata, Hiroaki; Kumasawa, Junji; Fukuma, Shingo; Mizobuchi, Masahide; Kinugasa, Eriko; Fukagawa, Masafumi; Fukuhara, Shunichi; Akizawa, Tadao

    2017-05-15

    The cardiothoracic ratio (CTR) is a non-invasive left ventricular hypertrophy index. However, whether CTR associates with cardiovascular disease (CVD) and mortality in hemodialysis (HD) populations is unclear. Using a Mineral and Bone disorder Outcomes Study for Japanese CKD Stage 5D Patients (MBD-5D Study) subcohort, 2266 prevalent HD patients (age 62.8 years, female 38.0%, HD duration 9.4 years) with secondary hyperparathyroidism (SHPT) whose baseline CTR had been recorded were selected. We evaluated associations between CTR and all-cause death, CVD death, or composite events in HD patients. CTR was associated significantly with various background and laboratory characteristics. All-cause death, CVD-related death, and composite events increased across the CTR quartiles (Q). Adjusted hazard risk (HR) for all-cause death was 1.4 (95% confidential interval, 0.9-2.1) in Q2, 1.9 (1.3-2.9) in Q3, and 2.6 (1.7-4.0) in Q4, respectively (Q1 as a reference). The corresponding adjusted HR for CVD-related death was 1.8 (0.8-4.2), 3.1 (1.4-6.8), and 3.5 (1.6-7.9), and that for composite outcome was 1.2 (1.0-1.6), 1.7 (1.3-2.2), and 1.8 (1.5-2.3), respectively. Exploratory analysis revealed that there were relationships between CTR and age, sex, body mass index, comorbidity of CVD, dialysis duration, dialysate calcium level and intact parathyroid hormone, phosphorus, hemoglobin, and usage of phosphate binder. CTR correlated with all-cause death, CVD death, and composite events in HD patients with SHPT.

  18. Prognostic impact of nutritional status assessed by the Controlling Nutritional Status score in patients with stable coronary artery disease undergoing percutaneous coronary intervention.

    PubMed

    Wada, Hideki; Dohi, Tomotaka; Miyauchi, Katsumi; Doi, Shinichiro; Konishi, Hirokazu; Naito, Ryo; Tsuboi, Shuta; Ogita, Manabu; Kasai, Takatoshi; Okazaki, Shinya; Isoda, Kikuo; Suwa, Satoru; Daida, Hiroyuki

    2017-06-20

    Recently, malnutrition has been shown to be related to worse clinical outcomes in patients with heart failure. However, the association between nutritional status and clinical outcomes in patients with coronary artery disease (CAD) remains unclear. We investigated the prognostic value of malnutrition assessed by the Controlling Nutritional Status (CONUT; range 0-12, higher = worse, consisting of serum albumin, cholesterol and lymphocytes) score in patients with CAD. The CONUT score was measured on admission in a total of 1987 patients with stable CAD who underwent elective percutaneous coronary intervention (PCI) between 2000 and 2011. Patients were divided into two groups according to their CONUT score (0-1 vs. ≥2). The incidence of major adverse cardiac events (MACE), including all-cause death and non-fatal myocardial infarction, was evaluated. The median CONUT score was 1 (interquartile range 0-2). During the median follow-up of 7.4 years, 342 MACE occurred (17.2%). Kaplan-Meier curves revealed that patients with high CONUT scores had higher rates of MACE (log-rank p < 0.0001). High CONUT scores showed a significant increase in the incidence of MACE compared with low CONUT scores, even after adjusting for confounding factors (hazard ratio: 1.64, 95% confidence interval 1.30-2.07, p < 0.0001). Adding CONUT scores to a baseline model with established risk factors improved the C-index (p = 0.02), net reclassification improvement (p = 0.004) and integrated discrimination improvement (p = 0.0003). Nutritional status assessed by the CONUT score was significantly associated with long-term clinical outcomes in patients with CAD. Pre-PCI assessment of the CONUT score may provide useful prognostic information.

  19. Weight loss and waist reduction is associated with improvement in gastroesophageal disease reflux symptoms: A longitudinal study of 15 295 subjects undergoing health checkups.

    PubMed

    Park, S-K; Lee, T; Yang, H-J; Park, J H; Sohn, C I; Ryu, S; Park, D I

    2017-05-01

    General obesity and abdominal obesity is an established risk factor of gastroesophageal reflux disease (GERD). However, the influence of weight or waist change on improvement of GERD is unclear. Our aim was to investigate if weight loss or waist reduction improves GERD symptoms and esophagitis. A retrospective longitudinal study of 15 295 subjects who underwent gastroscopy for a health checkup and reported GERD symptoms between 2011 and 2013, and repeated a checkup until 2014 was conducted. The improvement of GERD symptoms and esophagitis according to weight loss (≥-2, -0.5 to -2 kg/m(2) in body mass index [BMI]), waist reduction (≥-5, -0.1 to -0.5 cm) and baseline BMI/waist circumference (WC) categories was assessed using logistic regression. Weight loss or waist reduction was associated with improvement in GERD symptoms only in subjects with general or abdominal obesity. Among subjects with general obesity (BMI ≥25 kg/m(2) ) and decreased ≥2 kg/m(2) in BMI, the adjusted odds ratio (OR) of improvement in GERD symptoms was 2.34 (95% confidence interval [CI] 1.70-2.83). Among subjects with abdominal obesity (WC ≥90 cm) and decreased ≥5 cm in WC, the corresponding OR was 2.16 (95% CI 1.56-2.90). There was no association between weight loss or waist reduction and improvement in esophagitis. Weight loss or waist reduction was associated with improvement in GERD symptoms only in subjects with general or abdominal obesity. Weight loss or waist reduction will be an important treatment option in obese patients. © 2016 John Wiley & Sons Ltd.

  20. Factors Associated With Levels of Physical Activity in Chronic Kidney Disease Patients Undergoing Hemodialysis: The Role of Dialysis Versus Nondialysis Day.

    PubMed

    da Costa Rosa, Clara Suemi; Nishimoto, Danilo Yuzo; Freitas Júnior, Ismael Forte; Ciolac, Emmanuel Gomes; Monteiro, Henrique Luiz

    2017-09-01

    Patients on hemodialysis (HD) report lower physical activity (PA) levels. We analyzed factors associated with low levels of PA in patients with chronic kidney disease (CKD) and compared PA on HD day and non-HD. 79 patients wore an accelerometer and were classified according to time spent on moderate-to-vigorous PA (MVPA). Demographic data, BMI, comorbidities, clinical status, and health-related quality of life (HRQoL) were checked for association with PA. In addition, PA level was compared between days of HD and non-HD. Accelerometer compliance was 78.5% [33 men and 29 women (53.96 ± 15.71 yrs) were included in analysis]. 35.5% of sample achieved ≥150min/week on MVPA. Lower MVPA was associated with older age (OR = 5.80, 95% CI = 1.11 to 30.19, P = .04), and lower score of physical function HRQoL (OR = 4.33, 95% CI = 1.23 to 15.23, P = .02). In addition, patients spent 9.73% more time on sedentary behavior, 38.9% less on light PA and 74.9% less on MVPA on HD day versus non-HD day. Age and physical function HRQoL were the main factors associated to lower PA levels. In addition, lower time spent on PA during HD day suggest that strategies for increasing physical activity levels during HD day such exercising during HD session could help CKD patients to reach current PA recommendations.

  1. High-intensity training and cardiopulmonary exercise testing in patients with chronic obstructive pulmonary disease and non-small-cell lung cancer undergoing lobectomy.

    PubMed

    Stefanelli, Francesco; Meoli, Ilernando; Cobuccio, Raffaele; Curcio, Carlo; Amore, Dario; Casazza, Dino; Tracey, Maura; Rocco, Gaetano

    2013-10-01

    Peak VO2, as measure of physical performance is central to a correct preoperative evaluation in patients with both non-small-cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD) because it is closely related both to operability criteria and the rate of postoperative complications. Strategies to improve peak VO2, as a preoperative pulmonary rehabilitation programme (PRP), should be considered favourably in these patients. In order to clarify the role of pulmonary rehabilitation, we have evaluated the effects of 3-week preoperative high-intensity training on physical performance and respiratory function in a group of patients with both NSCLC and COPD who underwent lobectomy. We studied 40 patients with both NSCLC and COPD, age < 75 years, TNM stages I-II, who underwent lobectomy. Patients were randomly divided into two groups (R and S): Group R underwent an intensive preoperative PRP, while Group S underwent only lobectomy. We evaluated peak VO2 in all patients at Time 0 (T0), after PRP/before surgery in Group R/S (T1) and 60 days after surgery, respectively, in both groups (T2). There was no difference between groups in peak VO2 at T0, while a significant difference was observed both at T1 and T2. In Group R, peak VO2 improves significantly from T0 to T1: 14.9 ± 2.3-17.8 ± 2.1 ml/kg/min ± standard deviation (SD), P < 0.001 (64.5 ± 16.5-76.1 ± 14.9% predicted ± SD, P < 0.05) and deteriorates from T1 to T2: 17.8 ± 2.1-15.1 ± 2.4, P < 0.001 (76.1 ± 14.9-64.6 ± 15.5, P < 0.05), reverting to a similar value to that at T0, while in Group S peak VO2 did not change from T0 to T1 and significantly deteriorates from T1 to T2: 14.5 ± 1.2-11.4 ± 1.2 ml/kg/min ± SD, P < 0.00001 (60.6 ± 8.4-47.4 ± 6.9% predicted ± SD, P < 0.00001). PRP was a valid preoperative strategy to improve physical performance in patients with both NSCLC and COPD and this advantage was also maintained after surgery.

  2. Prevalence and Prognosis of Nonobstructive Coronary Artery Disease in Patients Undergoing Coronary Angiography or Coronary Computed Tomography Angiography: A Meta-Analysis.

    PubMed

    Wang, Zhi Jian; Zhang, Lin Lin; Elmariah, Sammy; Han, Hong Ya; Zhou, Yu Jie

    2017-03-01

    To evaluate the prevalence, clinical characteristics, and risk of cardiac events in patients with nonobstructive coronary artery disease (CAD). We searched PubMed, EMBASE, and the Cochrane Library from January 1, 1990, to November 31, 2015. Studies were included if they reported prevalence or prognosis of patients with nonobstructive CAD (≤50% stenosis) among patients with known or suspected CAD. Patients with nonobstructive CAD were further grouped as those with no angiographic CAD (0% or ≤20%) and those with mild CAD (>0% or >20% to ≤50%). Data were pooled using random effects modeling, and annualized event rates were assessed. Fifty-four studies with 1,395,190 participants were included. The prevalence of patients with nonobstructive CAD was 67% (95% CI, 63%-71%) among patients with stable angina and 13% (95% CI, 11%-16%) among patients with non-ST-segment elevation acute coronary syndrome. The prevalence varied depending on sex, clinical setting, and risk profile of the population investigated. The risk of hard cardiac events (cardiac death or myocardial infarction) in patients with mild CAD was lower than that in patients with obstructive CAD (risk ratio, 0.28; 95% CI, 0.20-0.38) but higher than that in those with no angiographic CAD (risk ratio, 1.85; 95% CI, 1.52-2.26). The annualized event rates of hard cardiac events in patients with no angiographic CAD, mild CAD, and obstructive CAD were 0.3% (95% CI, 0.1%-0.4%), 0.7% (95% CI, 0.5%-1.0%), and 2.7% (95% CI, 1.7%-3.7%), respectively, among patients with stable angina and 1.2% (95% CI, 0.02%-2.3%), 4.1% (95% CI, 3.3%-4.9%), and 17.0% (95% CI, 8.4%-25.7%) among patients with non-ST-segment elevation acute coronary syndrome. The correlation between CAD severity and prognosis is consistent regardless of clinical presentation of all-cause death, myocardial infarction, total cardiovascular events, and revascularization. Nonobstructive CAD is associated with a favorable prognosis compared with obstructive

  3. Exercise ventilatory inefficiency and mortality in patients with chronic obstructive pulmonary disease undergoing surgery for non-small-cell lung cancer.

    PubMed

    Torchio, Roberto; Guglielmo, Marco; Giardino, Roberto; Ardissone, Francesco; Ciacco, Claudio; Gulotta, Carlo; Veljkovic, Aleksandar; Bugiani, Massimiliano

    2010-07-01

    Surgical resection is the treatment of choice to cure patients with non-small-cell lung cancer (NSCLC); nevertheless, the assessment of the lower limit of surgical tolerance remains difficult. Ventilatory inefficiency (measured as the ventilation to CO(2) production ratio (V'(E)/V'(CO2) slope) is a survival predictor in pulmonary hypertension (PH) and chronic heart failure (CHF) and is considered a marker of PH in chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate the role of V'(E)/V'(CO2) slope as preoperative mortality and morbidity predictor in COPD patients submitted to lung resection for NSCLC and considered operable according to current standards. A retrospective analysis was performed in 145 consecutive COPD patients with lung cancer (128 males and 17 females), with a mean age of 64 years (range: 41-82 years) who were referred for preoperatory evaluation. Because of bronchial obstruction or reduced pulmonary diffusion capacity for carbon monoxide (D(L,CO)), all these patients were considered operable only after a cardiopulmonary exercise test showed a preserved cardiopulmonary function. A total of 98 lobectomies, eight bilobectomies and 39 pneumonectomies (13 left and 26 right) were performed. Twenty-one patients (14.5%) suffered severe cardio-respiratory complications; 15/106 patients (14.2%) after lobectomy/bilobectomy and 6/39 (15.4%) after pneumonectomy. Five patients (3.4%) died within 30 days after surgery (3/106 after lobectomy/bilobectomy (2.8%) and 2/39 after pneumonectomy (5.1%)). Considering all functional parameters before surgery and the postoperative predicted values, a logistic regression analysis individuated the V'(E)/V'(CO2) slope as the only independent mortality predictor (odds ratio (OR): 1.24 z=2.77; p<0.007). The V'(O2 peak) was instead the best predictor for the occurrence of severe cardiopulmonary postoperative complications (OR: 0.05, z=-2.39, p<0.02). In COPD patients, a high V'(E)/V'(CO2) slope

  4. Clinico-Pathological Profile and Surgical Outcome of Patients of Gastrointestinal Tuberculosis Undergoing Laparotomy.

    PubMed

    Pathak, Priyank; Sahu, Shantanu Kumar; Agrawal, Saurabh

    2016-01-01

    Tuberculosis is one of the earliest diseases affecting the mankind. Abdominal tuberculosis constitutes a common public health issue in developing countries like ours. Gastrointestinal tuberculosis often involves the ileocecal region. Surgery in case of abdominal tuberculosis is required to overcome the deleterious effects of the disease like tissue disorganization, obstruction and perforatio.

  5. 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

  6. 2017 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty.

    PubMed

    Goodman, Susan M; Springer, Bryan; Guyatt, Gordon; Abdel, Matthew P; Dasa, Vinod; George, Michael; Gewurz-Singer, Ora; Giles, Jon T; Johnson, Beverly; Lee, Steve; Mandl, Lisa A; Mont, Michael A; Sculco, Peter; Sporer, Scott; Stryker, Louis; Turgunbaev, Marat; Brause, Barry; Chen, Antonia F; Gililland, Jeremy; Goodman, Mark; Hurley-Rosenblatt, Arlene; Kirou, Kyriakos; Losina, Elena; MacKenzie, Ronald; Michaud, Kaleb; Mikuls, Ted; Russell, Linda; Sah, Alexander; Miller, Amy S; Singh, Jasvinder A; Yates, Adolph

    2017-08-01

    This collaboration between the American College of Rheumatology and the American Association of Hip and Knee Surgeons developed an evidence-based guideline for the perioperative management of antirheumatic drug therapy for adults with rheumatoid arthritis (RA), spondyloarthritis (SpA) including ankylosing spondylitis and psoriatic arthritis, juvenile idiopathic arthritis (JIA), or systemic lupus erythematosus (SLE) undergoing elective total hip (THA) or total knee arthroplasty (TKA). A panel of rheumatologists, orthopedic surgeons specializing in hip and knee arthroplasty, and methodologists was convened to construct the key clinical questions to be answered in the guideline. A multi-step systematic literature review was then conducted, from which evidence was synthesized for continuing versus withholding antirheumatic drug therapy and for optimal glucocorticoid management in the perioperative period. A Patient Panel was convened to determine patient values and preferences, and the Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence and the strength of recommendations, using a group consensus process through a convened Voting Panel of rheumatologists and orthopedic surgeons. The strength of the recommendation reflects the degree of certainty that benefits outweigh harms of the intervention, or vice versa, considering the quality of available evidence and the variability in patient values and preferences. The guideline addresses the perioperative use of antirheumatic drug therapy including traditional disease-modifying antirheumatic drugs, biologic agents, tofacitinib, and glucocorticoids in adults with RA, SpA, JIA, or SLE who are undergoing elective THA or TKA. It provides recommendations regarding when to continue, when to withhold, and when to restart these medications, and the optimal perioperative dosing of glucocorticoids. The guideline includes 7 recommendations, all of which are conditional

  7. 75 FR 41206 - Agency Forms Undergoing Paperwork Reduction Act Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-15

    ... 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 information... Chronic Disease Prevention and Control Programs--New--National Center for Chronic Disease Prevention...

  8. 78 FR 52532 - Agency Forms Undergoing Paperwork Reduction Act Review

    Federal Register 2010, 2011, 2012, 2013, 2014

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  9. The prevalence and social patterning of chronic diseases among older people in a population undergoing health transition. A 10/66 Group cross-sectional population-based survey in the Dominican Republic

    PubMed Central

    2010-01-01

    other settings undergoing the epidemiologic transition, the burden of risk factors shifts towards the less affluent. Monitoring future trends in the prevalence and social patterning of chronic diseases may help to assess the effectiveness and equity of primary and secondary prevention strategies. Specific recommendations from our research include identifying and targeting the causes of anaemia among older people, and addressing women's health disadvantages. PMID:20553582

  10. 'I'm worried about getting water in the holes in my head': A phenomenological psychology case study of the experience of undergoing deep brain stimulation surgery for Parkinson's disease.

    PubMed

    Eatough, Virginia; Shaw, Karen

    2017-02-01

    Deep brain stimulation (DBS) is a form of biotechnological surgery which has had considerable success for the motor improvement of Parkinson's disease and related disorders. Paradoxically, this observed motor improvement is not matched with improved psychosocial adjustment. This study contributes to a small but growing body of research aiming to understand this paradox. We conclude by discussing these aspects from a phenomenological and health psychology understanding of decision-making, human affectivity, and embodiment. A hermeneutic phenomenological case study. Semi-structured interviews with one woman with Parkinson's disease were carried out paying particular attention to (1) how the decision to have the procedure was made and (2) the affective experience in the time periods immediately prior to the procedure, shortly after and 1 month later. The thematic structure derived from the hermeneutic phenomenological analysis comprises the following experiential aspects: Making the decision: 'I was feeling rather at a dead end with my Parkinson's'; Shifting emotions and feelings: 'Terrified, excited, disappointed, overjoyed'; Embodied meaning: 'This extraordinary procedure where they were going to drill holes in my head'. This research has elucidated the complexity of decision-making, the emotional landscape, and specific bodily nature of the experience of DBS. It has suggested implications for practice informed by both existential-phenomenological theory and health psychology. Statement of contribution What is already known on this subject? Deep brain stimulation (DBS) is a newly developed form of biotechnological surgery and research indicates a mismatch between motor success and psychosocial adjustment. Most studies focuses on life post-DBS and there is relatively little research on how people make the decision to have the procedure, what their experience is of undergoing it including its emotional aspects. What does this study add? This study demonstrates that

  11. Hyposalivation after undergoing stapedectomy.

    PubMed

    Mandel, Louis

    2012-01-01

    Treatment for otosclerosis involves patients' undergoing stapedectomy. Inadvertent damage to the chorda tympani nerve's (CTN's) secretory fibers during stapedectomy can result in inadequate secretory stimulation of the submandibular salivary glands (SMSGs) and sublingual salivary glands (SLSGs). Because most saliva originates from these glands, hyposalivation and subjective xerostomia manifest during resting periods when parotid gland secretions are minimal. Stimulation with food increases parotid gland salivation enough to overcome the subjective sense of dryness. The author examined a 52-year-old man who had undergone bilateral stapedectomy because of hearing loss; his rheumatologist referred him to the Salivary Gland Center (New York City) because of a complaint of dry mouth. After the author examined the patient, he concluded that the patient had decreased SMSG and SLSG secretion and recommended that the patient use sugarless chewing gum or sour candy frequently to stimulate his parotid glands and use oral lubricants and sip water as needed. Stimulation of parotid gland secretion is independent of SMSG and SLSG activation. Therefore, the dental practitioner must become aware of the innervation of the salivary glands and each gland's secretory production during periods of oral stimulation and of rest.

  12. Culprit Vessel-Only vs. Staged Multivessel Percutaneous Coronary Intervention Strategies in Patients With Multivessel Coronary Artery Disease Undergoing Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction.

    PubMed

    Toyota, Toshiaki; Shiomi, Hiroki; Taniguchi, Tomohiko; Morimoto, Takeshi; Furukawa, Yutaka; Nakagawa, Yoshihisa; Horie, Minoru; Kimura, Takeshi

    2016-01-01

    We assessed the current status of treatment strategy in ST-segment elevation myocardial infarction (STEMI) with multivessel disease (MVD) in real world practice, focusing on the benefit of staged percutaneous coronary intervention (PCI). From the CREDO-Kyoto AMI Registry, 2,010 STEMI patients with MVD undergoing primary PCI were analyzed. Only 96 patients (4.8%) received acute multivessel PCI, and the majority of patients (n=1,914, 95.2%) had culprit-only PCI acutely. After excluding 699 patients (acute multivessel PCI, Killip class ≥3, age ≥90 years, coronary artery bypass grafting within 90 days, or clinical events within 90 days), 681 MVD patients underwent staged PCI for angiographically significant non-culprit lesions within 90 days (staged PCI group), while 630 MVD patients received primary PCI only (culprit-only PCI group). The cumulative 5-year incidence of and adjusted risk for all-cause death were significantly lower in the staged PCI group compared with the culprit-only PCI group (9.5% vs. 16.0%, P<0.001; HR, 0.69; 95% CI: 0.50-0.96, P=0.03). The risks for MI and any coronary revascularization favored the staged PCI strategy. The staged PCI strategy for angiographically significant non-culprit lesions was associated with lower 5-year mortality compared with the culprit-only PCI strategy in STEMI patients with MVD who underwent primary PCI.

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    ... HUMAN SERVICES Centers for Disease Control and Prevention Agency Forms Undergoing Paperwork Reduction... about 137,500 individuals. Information is collected using computer assisted personal interviews (CAPI..., health care services, health insurance, health conditions, and health behaviors. For 2014,...

  14. 75 FR 63485 - Agency Forms Undergoing Paperwork Reduction Act Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-15

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  15. The impact of chronic obstructive pulmonary disease on intensive care unit admission and 30-day mortality in patients undergoing colorectal cancer surgery: a Danish population-based cohort study.

    PubMed

    Platon, Anna Maria; Erichsen, Rune; Christiansen, Christian Fynbo; Andersen, Lea Kjær; Sværke, Claus; Montomoli, Jonathan; Sørensen, Henrik Toft

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) may increase the risk of postoperative complications and thus mortality after colorectal cancer (CRC) surgery, but the evidence is sparse. We conducted this nationwide population-based cohort study in Denmark, including all patients undergoing CRC surgery in the period 2005-2011, identified through medical databases. We categorised the patients according to the history of COPD. We assessed the rate of complications within 30 days. We computed 30-day mortality among patients with/without COPD using the Kaplan-Meier method. We used Cox regression to compute HRs for death, controlling for age, gender, type of admission, cancer stage, hospital volume, alcohol-related diseases, obesity and Charlson comorbidity score. We identified 18 302 CRC surgery patients. Of these, 7.9% had a prior diagnosis of COPD. Among patients with COPD, 16.1% were admitted postoperatively to the intensive care unit, 1.9% were treated with mechanical ventilation, and 3.6% were treated with non-invasive ventilation. In patients without COPD, the corresponding proportions were 9.7%, 1.1% and 1.1%. The reoperation rate was 10.6% among patients with COPD and 8% among patients with cancer without COPD. 30-day mortality was 13% (95% CI 11.4% to 14.9%) among patients with COPD and 5.3% (95% CI 5.0% to 5.7%) among patients without COPD, corresponding to an adjusted HR of 1.7 (95% CI 1.5 to 2.0). COPD is a strong predictor for intensive care unit admission and mortality after CRC surgery.

  16. The impact of chronic obstructive pulmonary disease on intensive care unit admission and 30-day mortality in patients undergoing colorectal cancer surgery: a Danish population-based cohort study

    PubMed Central

    Platon, Anna Maria; Erichsen, Rune; Christiansen, Christian Fynbo; Andersen, Lea Kjær; Sværke, Claus; Montomoli, Jonathan; Sørensen, Henrik Toft

    2014-01-01

    Background and purpose Chronic obstructive pulmonary disease (COPD) may increase the risk of postoperative complications and thus mortality after colorectal cancer (CRC) surgery, but the evidence is sparse. Methods We conducted this nationwide population-based cohort study in Denmark, including all patients undergoing CRC surgery in the period 2005–2011, identified through medical databases. We categorised the patients according to the history of COPD. We assessed the rate of complications within 30 days. We computed 30-day mortality among patients with/without COPD using the Kaplan-Meier method. We used Cox regression to compute HRs for death, controlling for age, gender, type of admission, cancer stage, hospital volume, alcohol-related diseases, obesity and Charlson comorbidity score. Results We identified 18 302 CRC surgery patients. Of these, 7.9% had a prior diagnosis of COPD. Among patients with COPD, 16.1% were admitted postoperatively to the intensive care unit, 1.9% were treated with mechanical ventilation, and 3.6% were treated with non-invasive ventilation. In patients without COPD, the corresponding proportions were 9.7%, 1.1% and 1.1%. The reoperation rate was 10.6% among patients with COPD and 8% among patients with cancer without COPD. 30-day mortality was 13% (95% CI 11.4% to 14.9%) among patients with COPD and 5.3% (95% CI 5.0% to 5.7%) among patients without COPD, corresponding to an adjusted HR of 1.7 (95% CI 1.5 to 2.0). Conclusions COPD is a strong predictor for intensive care unit admission and mortality after CRC surgery. PMID:25478184

  17. Comparison of Time Trends of Cardiovascular Disease Risk Factors and Framingham Risk Score Between Patients With and Without Acute Coronary Syndrome Undergoing Percutaneous Intervention Over the Last 17 Years: From the Mayo Clinic Percutaneous Coronary Intervention Registry.

    PubMed

    Lee, Moo-Sik; Flammer, Andreas J; Li, Jing; Lennon, Ryan J; Delacroix, Sinny; Kim, Hyunsoo; Lerman, Amir

    2015-12-01

    The objective of this study was to investigate cardiovascular disease risk factor (cvRF) profiles and compare their trends over 17 years in patients with and without acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Time trends of cvRF are different between ACS and non-ACS patients. This study was a time-trend analysis from 1994 to 2010 within the Mayo Clinic PCI registry. Outcome measures were incidence and prevalence of cvRF, including the Framingham Risk Score (FRS), at the time of admission for PCI. Age of non-ACS patients was higher than that of ACS patients, and age distribution slightly shifted toward older age in both groups (P for trend <0.001). There was no difference in FRS between the 2 groups; however, 10-year cardiovascular disease risk (%) remained higher in non-ACS than in ACS patients, decreasing over time. Diastolic blood pressure and high-density lipoprotein cholesterol were higher in non-ACS patients, but total cholesterol and low-density lipoprotein cholesterol were higher in ACS patients, with an improving trend over time. Prevalence of diabetes mellitus, hypertension, and history of hypercholesterolemia were higher in non-ACS patients, increasing over time. Smoking did not change over time. Use of most medications increased over time in both groups. Most cvRFs and their time trends exhibited statistically significant differences between ACS and non-ACS patients, except systolic blood pressure, body mass index, and history of myocardial infarction. A new risk-factor profile assessment may be needed for stratification of PCI patients according to ACS and non-ACS status. Clinical and public-health interventions should consider different approaches to ACS and non-ACS patients. © 2015 Wiley Periodicals, Inc.

  18. Gender differences in the prevalence, severity, and composition of coronary artery disease in the young: a study of 1635 individuals undergoing coronary CT angiography from the prospective, multinational confirm registry

    PubMed Central

    Otaki, Yuka; Gransar, Heidi; Cheng, Victor Y.; Dey, Damini; Labounty, Troy; Lin, Fay Y.; Achenbach, Stephan; Al-Mallah, Mouaz; Budoff, Matthew J.; Cademartiri, Filippo; Callister, Tracy Q.; Chang, Hyuk-Jae; Chinnaiyan, Kavitha; Chow, Benjamin J.W.; Delago, Augustin; Hadamitzky, Martin; Hausleiter, Joerg; Kaufmann, Philipp; Maffei, Erica; Raff, Gilbert; Shaw, Leslee J.; Villines, Todd C.; Dunning, Allison; Cury, Ricardo C.; Feuchtner, Gudrun; Kim, Yong-Jin; Leipsic, Jonathon; Berman, Daniel S.; Min, James K.

    2015-01-01

    Objective Prior studies examining coronary atherosclerosis in the young have been limited by retrospective analyses in small cohorts. We examined the relationship between cardiovascular risk factors (RFs) and prevalence and severity of coronary atherosclerosis in a large, prospective, multinational registry of consecutive young individuals undergoing coronary computerized tomographic angiography (CCTA). Method and results Of 27 125 patients undergoing CCTA, 1635 young (<45 years) individuals without known coronary artery disease (CAD) or coronary anomalies were identified. Coronary plaque was assessed for any CAD, obstructive CAD (≥50% stenosis), and presence of calcified plaque (CP) and non-calcified plaque (NCP). Among 1635 subjects (70% men, age 38 ± 6 years), any CAD, obstructive CAD, CP, and NCP were observed in 19, 4, 5, and 8%, respectively. Compared with women, men demonstrated higher rates of any CAD (21 vs. 12%, P < 0.001), CP (6 vs. 3%, P = 0.01), and NCP (9 vs. 5%, P = 0.008), although no difference was observed for rates of obstructive CAD (5 vs. 4%, P = 0.46). Any CAD, obstructive CAD, and NCP were higher for young individuals with diabetes, hypertension, dyslipidaemia, current smoking, or family history of CAD; while only diabetes and dyslipidaemia were associated with CP. Increasing cardiovascular RFs was associated with a greater prevalence and extent and severity of CAD, with individuals with 0, 1, 2, ≥3 RFs manifesting a dose–response increase in any CAD (P < 0.001, for trend), obstructive CAD (P < 0.001, for trend), NCP (P < 0.001, for trend), and CP (P < 0.001, for trend). In multivariable analysis adjusting for sex and cardiovascular RFs, male sex was the strongest predictor for any CAD (odds ratio [OR] = 1.95, 95% confidence interval [CI] = 1.43–2.66, P < 0.001), CP (OR = 1.46, 95% CI = 1.08–1.98, P = 0.01), and NCP (OR = 1.33, 95% CI = 1.06–1.67, P = 0.01); family history of CAD was the strongest predictor for obstructive CAD

  19. Short-Term High-Dose Vitamin E to Prevent Contrast Medium-Induced Acute Kidney Injury in Patients With Chronic Kidney Disease Undergoing Elective Coronary Angiography: A Randomized Placebo-Controlled Trial.

    PubMed

    Rezaei, Yousef; Khademvatani, Kamal; Rahimi, Behzad; Khoshfetrat, Mehran; Arjmand, Nasim; Seyyed-Mohammadzad, Mir-Hossein

    2016-03-15

    Contrast medium-induced acute kidney injury (CIAKI) is a leading cause of acquired renal impairment. The effects of antioxidants have been conflicting regarding the prevention of CIAKI. We performed a study of vitamin E use to decrease CIAKI in patients undergoing elective coronary angiography. In a placebo-controlled randomized trial at 2 centers in Iran, 300 patients with chronic kidney disease-defined as estimated glomerular filtration rate <60 mL/min per 1.73 m(2)-were randomized 1:1 to receive 0.9% saline infusion 12 hours prior to and after intervention combined with 600 mg vitamin E 12 hours before plus 400 mg vitamin E 2 hours before coronary angiography or to receive placebo. The primary end point was the development of CIAKI, defined as an increase ≥0.5 mg/dL or ≥25% in serum creatinine that peaked within 72 hours. Based on an intention-to-treat analysis, CIAKI developed in 10 (6.7%) and 21 (14.1%) patients in the vitamin E and placebo groups, respectively (P=0.037). Change in white blood cell count from baseline to peak value was greater in the vitamin E group compared with the placebo group (-500 [-1500 to 200] versus 100 [-900 to 600]×10(3)/mL, P=0.001). In multivariate analysis, vitamin E (odds ratio 0.408, 95% CI 0.170-0.982, P=0.045) and baseline Mehran score (odds ratio 1.257, 95% CI 1.007-1.569; P=0.043) predicted CIAKI. Prophylactic short-term high-dose vitamin E combined with 0.9% saline infusion is superior to placebo for prevention of CIAKI in patients undergoing elective coronary angiography. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02070679. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  20. A randomized comparison of 1-h sodium bicarbonate hydration versus standard peri-procedural saline hydration in patients with chronic kidney disease undergoing intravenous contrast-enhanced computerized tomography.

    PubMed

    Kooiman, Judith; Sijpkens, Yvo W J; de Vries, Jean-Paul P M; Brulez, Harald F H; Hamming, Jaap F; van der Molen, Aart J; Aarts, Nico J M; Cannegieter, Suzanne C; Putter, Hein; Swarts, Renate; van den Hout, Wilbert B; Rabelink, Ton J; Huisman, Menno V

    2014-05-01

    Guidelines recommend saline hydration for prophylaxis of contrast-induced acute kidney injury (CI-AKI) in patients with chronic kidney disease (CKD) undergoing intravenous contrast media-enhanced CT (CE-CT). The safety and efficacy of a brief hydration protocol using sodium bicarbonate in this population is unknown. We analysed whether 1-h sodium bicarbonate hydration prior to CE-CT is non-inferior to saline hydration prior to and after CE-CT in CKD patients. We performed an open-label multicentre randomized trial. Patients were randomized to 250 mL of 1.4% sodium bicarbonate hydration prior to CE-CT or 1000 mL of 0.9% saline hydration prior to and, once again, after CE-CT. Primary outcome was the relative increase in serum creatinine 48-96 h post-CE-CT. Secondary outcomes were incidence of CI-AKI [serum creatinine increase >25%/>44 µmol/L (0.5 mg/dL)], recovery of renal function, the need for dialysis and 2-month hospital costs. Five hundred and seventy adult CKD patients undergoing CE-CT were randomized between 2010 and 2012, of whom 548 were included in the intention-to-treat population. Mean relative serum creatinine increase was 1.2% for sodium bicarbonate and 1.5% for saline (mean difference -0.3%; 95% confidence interval -2.7 to 2.1, P-value for non-inferiority <0.0001). CI-AKI occurred in 22 patients (4.1%); 8 (3.0%) randomized to sodium bicarbonate versus 14 (5.1%) to saline (P = 0.23). Renal function recovered in 75 and 69% of CI-AKI patients, respectively (P = 0.81). No patients developed a need for dialysis. Mean hydration costs per patient were €224 for the sodium bicarbonate and €683 for the saline regime (P < 0.001). Other healthcare costs were similar. Short hydration with sodium bicarbonate prior to CE-CT was non-inferior to peri-procedural saline hydration with respect to renal safety and may result in healthcare savings. [Netherlands Trial Register (http://www.trialregister.nl/trialreg/index.asp), Nr 2149, date of registration 23 December

  1. Impact of Conditioning Regimen on Outcomes for Children with Acute Myeloid Leukemia Undergoing Transplantation in First Complete Remission. An Analysis on Behalf of the Pediatric Disease Working Party of the European Group for Blood and Marrow Transplantation.

    PubMed

    Lucchini, Giovanna; Labopin, Myriam; Beohou, Eric; Dalissier, Arnauld; Dalle, Jean Hughes; Cornish, Jacqueline; Zecca, Marco; Samarasinghe, Sujith; Gibson, Brenda; Locatelli, Franco; Bertrand, Yves; Abdel-Rahman, Fawzi; Socie, Gerald; Sundin, Mikael; Lankester, Arjan; Sedlacek, Peter; Hamladji, Rose Marie; Heilmann, Carsten; Afanasyev, Boris; Hough, Rachel; Peters, Cristina; Bader, Peter; Veys, Paul

    2017-03-01

    Hematopoietic stem cell transplantation (HSCT) represents the cornerstone of treatment in pediatric high-risk and relapsed acute myeloid leukemia (AML). The aim of the present study was to compare outcomes of pediatric patients with AML undergoing HSCT using 3 different conditioning regimens: total body irradiation (TBI) and cyclophosphamide (Cy); busulfan (Bu) and Cy; or Bu, Cy, and melphalan (Mel). In this retrospective study, registry data for patients > 2 and <18 years age undergoing matched allogeneic HSCT for AML in first complete remission (CR1) in 204 European Group for Blood and Marrow Transplantation centers between 2000 and 2010 were analyzed. Data were available for 631 patients; 458 patients received stem cells from a matched sibling donor and 173 from a matched unrelated donor. For 440 patients, bone marrow was used as stem cell source, and 191 patients received peripheral blood stem cells. One hundred nine patients received TBICy, 389 received BuCy, and 133 received BuCyMel as their preparatory regimen. Median follow-up was 55 months. Patients receiving BuCyMel showed a lower incidence of relapse at 5 years (14.7% versus 31.5% in BuCy versus 30% in TBICy, P < .01) and higher overall survival (OS) (76.6% versus 64% versus 64.5%, P = .04) and leukemia-free survival (LFS) (74.5% versus 58% versus 61.9%, P < .01), with a comparable nonrelapse mortality (NRM) (10.8% versus 10.5% versus 8.1%, P = .79). Acute graft-versus-host disease (GVHD) grades III and IV but not chronic GVHD, was higher in patients receiving BuCyMel. Older age at HSCT had an adverse impact on NRM and the use of peripheral blood as stem cell source was associated with increased chronic GVHD and NRM as well as lower LFS and OS. Among pediatric patients receiving HSCT for AML in CR1, the use of BuCyMel conditioning proved superior to TBICy and BuCy in reducing relapse and improving LFS.

  2. Gender differences in the prevalence, severity, and composition of coronary artery disease in the young: a study of 1635 individuals undergoing coronary CT angiography from the prospective, multinational confirm registry.

    PubMed

    Otaki, Yuka; Gransar, Heidi; Cheng, Victor Y; Dey, Damini; Labounty, Troy; Lin, Fay Y; Achenbach, Stephan; Al-Mallah, Mouaz; Budoff, Matthew J; Cademartiri, Filippo; Callister, Tracy Q; Chang, Hyuk-Jae; Chinnaiyan, Kavitha; Chow, Benjamin J W; Delago, Augustin; Hadamitzky, Martin; Hausleiter, Joerg; Kaufmann, Philipp; Maffei, Erica; Raff, Gilbert; Shaw, Leslee J; Villines, Todd C; Dunning, Allison; Cury, Ricardo C; Feuchtner, Gudrun; Kim, Yong-Jin; Leipsic, Jonathon; Berman, Daniel S; Min, James K

    2015-05-01

    Prior studies examining coronary atherosclerosis in the young have been limited by retrospective analyses in small cohorts. We examined the relationship between cardiovascular risk factors (RFs) and prevalence and severity of coronary atherosclerosis in a large, prospective, multinational registry of consecutive young individuals undergoing coronary computerized tomographic angiography (CCTA). Of 27 125 patients undergoing CCTA, 1635 young (<45 years) individuals without known coronary artery disease (CAD) or coronary anomalies were identified. Coronary plaque was assessed for any CAD, obstructive CAD (≥50% stenosis), and presence of calcified plaque (CP) and non-calcified plaque (NCP). Among 1635 subjects (70% men, age 38 ± 6 years), any CAD, obstructive CAD, CP, and NCP were observed in 19, 4, 5, and 8%, respectively. Compared with women, men demonstrated higher rates of any CAD (21 vs. 12%, P < 0.001), CP (6 vs. 3%, P = 0.01), and NCP (9 vs. 5%, P = 0.008), although no difference was observed for rates of obstructive CAD (5 vs. 4%, P = 0.46). Any CAD, obstructive CAD, and NCP were higher for young individuals with diabetes, hypertension, dyslipidaemia, current smoking, or family history of CAD; while only diabetes and dyslipidaemia were associated with CP. Increasing cardiovascular RFs was associated with a greater prevalence and extent and severity of CAD, with individuals with 0, 1, 2, ≥3 RFs manifesting a dose-response increase in any CAD (P < 0.001, for trend), obstructive CAD (P < 0.001, for trend), NCP (P < 0.001, for trend), and CP (P < 0.001, for trend). In multivariable analysis adjusting for sex and cardiovascular RFs, male sex was the strongest predictor for any CAD (odds ratio [OR] = 1.95, 95% confidence interval [CI] = 1.43-2.66, P < 0.001), CP (OR = 1.46, 95% CI = 1.08-1.98, P = 0.01), and NCP (OR = 1.33, 95% CI = 1.06-1.67, P = 0.01); family history of CAD was the strongest predictor for obstructive CAD (OR = 2.71, 95% CI = 1.65-4.45, P < 0

  3. 2017 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty.

    PubMed

    Goodman, Susan M; Springer, Bryan; Guyatt, Gordon; Abdel, Matthew P; Dasa, Vinod; George, Michael; Gewurz-Singer, Ora; Giles, Jon T; Johnson, Beverly; Lee, Steve; Mandl, Lisa A; Mont, Michael A; Sculco, Peter; Sporer, Scott; Stryker, Louis; Turgunbaev, Marat; Brause, Barry; Chen, Antonia F; Gililland, Jeremy; Goodman, Mark; Hurley-Rosenblatt, Arlene; Kirou, Kyriakos; Losina, Elena; MacKenzie, Ronald; Michaud, Kaleb; Mikuls, Ted; Russell, Linda; Sah, Alexander; Miller, Amy S; Singh, Jasvinder A; Yates, Adolph

    2017-09-01

    This collaboration between the American College of Rheumatology and the American Association of Hip and Knee Surgeons developed an evidence-based guideline for the perioperative management of antirheumatic drug therapy for adults with rheumatoid arthritis (RA), spondyloarthritis (SpA) including ankylosing spondylitis and psoriatic arthritis, juvenile idiopathic arthritis (JIA), or systemic lupus erythematosus (SLE) undergoing elective total hip (THA) or total knee arthroplasty (TKA). A panel of rheumatologists, orthopedic surgeons specializing in hip and knee arthroplasty, and methodologists was convened to construct the key clinical questions to be answered in the guideline. A multi-step systematic literature review was then conducted, from which evidence was synthesized for continuing versus withholding antirheumatic drug therapy and for optimal glucocorticoid management in the perioperative period. A Patient Panel was convened to determine patient values and preferences, and the Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence and the strength of recommendations, using a group consensus process through a convened Voting Panel of rheumatologists and orthopedic surgeons. The strength of the recommendation reflects the degree of certainty that benefits outweigh harms of the intervention, or vice versa, considering the quality of available evidence and the variability in patient values and preferences. The guideline addresses the perioperative use of antirheumatic drug therapy including traditional disease-modifying antirheumatic drugs, biologic agents, tofacitinib, and glucocorticoids in adults with RA, SpA, JIA, or SLE who are undergoing elective THA or TKA. It provides recommendations regarding when to continue, when to withhold, and when to restart these medications, and the optimal perioperative dosing of glucocorticoids. The guideline includes 7 recommendations, all of which are conditional

  4. 75 FR 18503 - Agency Forms Undergoing Paperwork Reduction Act Review

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    2010-04-12

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  8. 78 FR 64502 - Agency Forms Undergoing Paperwork Reduction Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-29

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  9. 76 FR 44337 - Agency Forms Undergoing Paperwork Reduction Act Review

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  10. 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

  11. 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

    dos Reis Santos, Israel; Danaga, Aline Roberta; de Carvalho Aguiar, Isabella; Oliveira, Ezequiel Fernandes; Dias, Ismael Souza; Urbano, Jessica Julioti; Martins, Aline Almeida; Ferraz, Leonardo Macario; Fonsêca, Nina Teixeira; Fernandes, Virgilio; Fernandes, Vinicius Alves Thomaz; Lopes, Viviane Cristina Delgado; Leitão Filho, Fernando Sérgio Studart; Nacif, Sérgio Roberto; de Carvalho, Paulo de Tarso Camillo; Sampaio, Luciana Maria Malosá; Giannasi, Lílian Christiane; Romano, Salvatore; Insalaco, Giuseppe; Araujo, Ana Karina Fachini; Dellê, Humberto; Souza, Nadia Karina Guimarães; Giannella-Neto, Daniel; Oliveira, Luis Vicente Franco

    2013-10-08

    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. 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/height(2); 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. 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. The protocol for this study is registered with the Brazilian

  12. A disease-specific enteral nutrition formula improves nutritional status and functional performance in patients with head and neck and esophageal cancer undergoing chemoradiotherapy: results of a randomized, controlled, multicenter trial.

    PubMed

    Fietkau, Rainer; Lewitzki, Victor; Kuhnt, Thomas; Hölscher, Tobias; Hess, Clemens-F; Berger, Bernhard; Wiegel, Thomas; Rödel, Claus; Niewald, Marcus; Hermann, Robert M; Lubgan, Dorota

    2013-09-15

    In patients with head and neck and esophageal tumors, nutritional status may deteriorate during concurrent chemoradiotherapy (CRT). The aim of this study was to investigate the influence of enteral nutrition enriched with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on body composition and nutritional and functional status. In a controlled, randomized, prospective, double-blind, multicenter study, 111 patients with head and neck and esophageal cancer undergoing concurrent CRT received either an enteral standard nutrition (control group) or disease-specific enteral nutrition Supportan®-containing EPA+DHA (experimental group) via percutaneous endoscopic gastrostomy. The primary endpoint was the change of body cell mass (BCM) following CRT at weeks 7 and 14 compared with the baseline value. Secondary endpoints were additional parameters of body composition, anthropometric parameters, and nutritional and functional status. The primary endpoint of the study, improvement in BCM, reached borderline statistical significance. Following CRT, patients with experimental nutrition lost only 0.82 ± 0.64 kg of BCM compared with 2.82 ± 0.77 kg in the control group (P = .055). The objectively measured nutritional parameters, such as body weight and fat-free mass, showed a tendency toward improvement, but the differences were not significant. The subjective parameters, in particular the Kondrup score (P = .0165) and the subjective global assessment score (P = .0065) after follow-up improved significantly in the experimental group, compared with the control group. Both enteral regimens were safe and well tolerated. Enteral nutrition with EPA and DHA may be advantageous in patients with head and neck or esophageal cancer by improving parameters of nutritional and functional status during CRT. © 2013 American Cancer Society.

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

    PubMed

    Faraoni, David; Van der Linden, Philippe

    2014-02-11

    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.

  14. 76 FR 34705 - Agency Forms Undergoing Paperwork Reduction Act Review

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  15. <