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1

GM1 gangliosidosis: clinical and laboratory findings in eight families.  

PubMed

GM1 Gangliosidosis is an autosomal recessive genetic disorder due to deficiency of the lysosome enzyme beta-galactosidase, with consequent tissue accumulation of glycolipids, oligosaccharides, and especially GM1 ganglioside. In the present paper we report the clinical and laboratory findings obtained for eight families starting from eight index cases exhibiting the childhood form of the disease. The total number of cases in these families may be as high as 14, thus causing GM1 gangliosidosis to be the inborn metabolic error most frequently diagnosed in our service. Hypotonia, neuromotor retardation, hepatosplenomegaly, macrocephaly, and hydrocele are some of the most frequent clinical findings. The disease evolves towards convulsions and bronchopneumonia, leading to patient death generally during the first half of the second year of life. The presence of vacuolated lymphocytes, alterations of the lumbar vertebrae, and cherry spots on the retina were observed in almost all patients. When tested for inborn metabolic errors, all patients gave normal results, a fact that may have confused and delayed diagnosis. Diagnosis was made by urine oligosaccharide chromatography and confirmed by beta-galactoside measurement in peripheral blood leukocytes. This method proved to be accurate also for the detection of heterozygotes, which permitted post-mortem diagnosis in two families. The authors speculate that increased fetal loss and tendency towards macrosomy may be possible characteristics of the disease, suggest that testing for vacuolated lymphocytes be used as a screening method, and propose that urine oligosaccharide chromatography be included in the routine screening for inborn metabolic errors. PMID:3926630

Giugliani, R; Dutra, J C; Pereira, M L; Rotta, N; Drachler, M de L; Ohlweiller, L; Pina Neto, J M; Pinheiro, C E; Breda, D J

1985-01-01

2

962. Treatment of Feline GM1 Gangliosidosis with Mesenchymal Stem Cells and Lentiviral Gene Therapy  

Microsoft Academic Search

Deficiency of lysosomal ?-galactosidase causes GM1 gangliosidosis, an inherited, progressive neurological disorder in which GM1 ganglioside accumulates in all tissues, including thymus, liver and brain. In addition to abnormal neuronal histology and function, gangliosidosis pathology involves a significant inflammatory component and therefore is similar to other neurodegenerative disorders such as Alzheimer and Parkinson disease. GM1 gangliosidosis occurs in humans, mice

Douglas R. Martin; Karin Haack; Glenn P. Niemeyer; Nancy R. Cox; Tal Kafri; Henry J. Baker

2005-01-01

3

Chronic GM1 gangliosidosis presenting as dystonia: clinical and biochemical studies in a new case.  

PubMed

Clinical and biochemical findings in a patient affected by chronic GM1 gangliosidosis, presenting as progressive dystonia and mental deterioration, are reported. The patient, a 13-year-old male, showed, at the age of 3 years, an impairment of gait with frequent falls, dysarthria and stuttering. At the age of 6, writing dystonia appeared and subsequently mental deterioration and dystonic postures of arms and legs became evident. The clinical features presented by this patient are similar to those shown by the cases of adult/chronic GM1 gangliosidosis previously reported, except for the early onset. This observation emphasizes the occurrence of dystonia as prominent symptom in chronic GM1 gangliosidosis, underlining that this disease must be considered in the diagnostic approach to the progressive dystonias of the early infancy. PMID:8355822

Nardocci, N; Bertagnolio, B; Rumi, V; Combi, M; Bardelli, P; Angelini, L

1993-06-01

4

GM1 gangliosidosis and Morquio B disease: an update on genetic alterations and clinical findings.  

PubMed

GM1 gangliosidosis and Morquio B syndrome, both arising from beta-galactosidase (GLB1) deficiency, are very rare lysosomal storage diseases with an incidence of about 1:100,000-1:200,000 live births worldwide. Here we report the beta-galactosidase gene (GLB1) mutation analysis of 21 unrelated GM1 gangliosidosis patients, and of 4 Morquio B patients, of whom two are brothers. Clinical features of the patients were collected and compared with those in literature. In silico analyses were performed by standard alignments tools and by an improved version of GLB1 three-dimensional models. The analysed cohort includes remarkable cases. One patient with GM1 gangliosidosis had a triple X syndrome. One patient with juvenile GM1 gangliosidosis was homozygous for a mutation previously identified in Morquio type B. A patient with infantile GM1 gangliosidosis carried a complex GLB1 allele harbouring two genetic variants leading to p.R68W and p.R109W amino acid changes, in trans with the known p.R148C mutation. Molecular analysis showed 27 mutations, 9 of which are new: 5 missense, 3 microdeletions and a nonsense mutation. We also identified four new genetic variants with a predicted polymorphic nature that was further investigated by in silico analyses. Three-dimensional structural analysis of GLB1 homology models including the new missense mutations and the p.R68W and p.R109W amino acid changes showed that all the amino acid replacements affected the resulting protein structures in different ways, from changes in polarity to folding alterations. Genetic and clinical associations led us to undertake a critical review of the classifications of late-onset GM1 gangliosidosis and Morquio B disease. PMID:21497194

Caciotti, Anna; Garman, Scott C; Rivera-Colón, Yadilette; Procopio, Elena; Catarzi, Serena; Ferri, Lorenzo; Guido, Carmen; Martelli, Paola; Parini, Rossella; Antuzzi, Daniela; Battini, Roberta; Sibilio, Michela; Simonati, Alessandro; Fontana, Elena; Salviati, Alessandro; Akinci, Gulcin; Cereda, Cristina; Dionisi-Vici, Carlo; Deodato, Francesca; d'Amico, Adele; d'Azzo, Alessandra; Bertini, Enrico; Filocamo, Mirella; Scarpa, Maurizio; di Rocco, Maja; Tifft, Cynthia J; Ciani, Federica; Gasperini, Serena; Pasquini, Elisabetta; Guerrini, Renzo; Donati, Maria Alice; Morrone, Amelia

2011-07-01

5

GM1 gangliosidosis and Morquio B disease: an update on genetic alterations and clinical findings  

PubMed Central

GM1 gangliosidosis and Morquio B syndrome, both arising from beta-galactosidase (GLB1) deficiency, are very rare lysosomal storage diseases with an incidence of about 1:100,000– 1:200,000 live births worldwide. Here we report the beta-galactosidase gene (GLB1) mutation analysis of 21 unrelated GM1 gangliosidosis patients, and of 4 Morquio B patients, of whom two are brothers. Clinical features of the patients were collected and compared with those in literature. In silico analyses were performed by standard alignments tools and by an improved version of GLB1 three-dimensional models. The analysed cohort includes remarkable cases. One patient with GM1 gangliosidosis had a triple X syndrome. One patient with juvenile GM1 gangliosidosis was homozygous for a mutation previously identified in Morquio type B. A patient with infantile GM1 gangliosidosis carried a complex GLB1 allele harbouring two genetic variants leading to p.R68W and p.R109W amino acid changes, in trans with the known p.R148C mutation. Molecular analysis showed 27 mutations, 9 of which are new: 5 missense, 3 microdeletions and a nonsense mutation. We also identified four new genetic variants with a predicted polymorphic nature that was further investigated by in silico analyses. Three-dimensional structural analysis of GLB1 homology models including the new missense mutations and the p.R68W and p.R109W amino acid changes, showed that all the amino acids replacements affected the resulting protein structures in different ways, from changes in polarity to folding alterations. Genetic and clinical associations led us to undertake a critical review of the classifications of late-onset GM1 gangliosidosis and Morquio B disease. PMID:21497194

Caciotti, Anna; Garman, Scott C; Rivera-Colón, Yadilette; Procopio, Elena; Catarzi, Serena; Ferri, Lorenzo; Guido, Carmen; Martelli, Paola; Parini, Rossella; Antuzzi, Daniela; Battini, Roberta; Sibilio, Michela; Simonati, Alessandro; Fontana, Elena; Salviati, Alessandro; Akinci, Gulcin; Cereda, Cristina; Dionisi-Vici, Carlo; Deodato, Francesca; d’Amico, Adele; d’Azzo, Alessandra; Bertini, Enrico; Filocamo, Mirella; Scarpa, Maurizio; di Rocco, Maja; Tifft, Cynthia J; Ciani, Federica; Gasperini, Serena; Pasquini, Elisabetta; Guerrini, Renzo; Donati, Maria Alice; Morrone, Amelia

2011-01-01

6

Filipin recognizes both GM1 and cholesterol in GM1 gangliosidosis mouse brain  

PubMed Central

Filipin is an antibiotic polyene widely used as a histochemical marker for cholesterol. We previously reported cholesterol/filipin-positive staining in brain of ?-galactosidase (?-gal) knockout (?/?) mice (GM1 gangliosidosis). The content and distribution of cholesterol and gangliosides was analyzed in plasma membrane (PM) and microsomal (MS) fractions from whole-brain tissue of 15 week-old control (?-gal+/?) and GM1 gangliosidosis (?-gal?/?) mice. Total ganglioside content (?g sialic acid/mg protein) was 3-fold and 7-fold greater in the PM and MS fractions, respectively, in ?gal?/? mice than in ?gal+/? mice. GM1 content was 30-fold and 50-fold greater in the PM and MS fractions, respectively. In contrast, unesterified cholesterol content (?g/mg protein) was similar in the PM and the MS fractions of the ?gal?/? and ?gal+/? mice. Filipin is known to bind to various sterol derivatives and phospholipids on thin-layer chromatograms. Biochemical evidence is presented showing that filipin also binds to GM1 with an affinity similar to that for cholesterol, with a corresponding fluorescent reaction. Our data suggest that the GM1 storage seen in the ?-gal?/? mouse contributes to the filipin ultraviolet fluorescence observed in GM1 gangliosidosis brain. The data indicate that in addition to cholesterol, filipin can also be useful for detecting GM1. PMID:21508255

Arthur, Julian R.; Heinecke, Karie A.; Seyfried, Thomas N.

2011-01-01

7

Chemical chaperone therapy for brain pathology in GM1-gangliosidosis  

Microsoft Academic Search

We synthesized a galactose derivative, N-octyl-4-epi--valienamine (NOEV), for a molecular therapy (chemical chaperone therapy) of a human neurogenetic disease, -galactosidosis (GM1-gangliosidosis and Morquio B disease). It is a potent inhibitor of lysosomal -galactosidase in vitro. Addition of NOEV in the culture medium restored mutant enzyme activity in cultured human or murine fibroblasts at low intracellular concentrations, resulting in a marked

Junichiro Matsuda; Osamu Suzuki; Akihiro Oshima; Yoshie Yamamoto; Akira Noguchi; Kazuhiro Takimoto; Masayuki Itoh; Yuji Matsuzaki; Yosuke Yasuda; Seiichiro Ogawa; Yuko Sakata; Eiji Nanba; Katsumi Higaki; Yoshimi Ogawa; Lika Tominaga; Kousaku Ohno; Hiroyuki Iwasaki; Hiroshi Watanabe; Roscoe O. Brady; Yoshiyuki Suzuki

2003-01-01

8

Chaperone therapy update: Fabry disease, GM1-gangliosidosis and Gaucher disease.  

PubMed

Chaperone therapy is a newly developed molecular therapeutic approach to lysosomal diseases, a group of human genetic diseases causing severe brain damage. Based on early molecular studies during the last decade of the 20th century and early years of the 21st century, mainly on Fabry disease and GM1-gangliosidosis, we found some mutant enzyme proteins were unstable in the cell, and unable to express catalytic activities. Subsequently galactose and other active-site binding substrate analogs were found stabilized and enhance the mutant enzyme activity in culture cells. We concluded that the mutant misfolding enzyme protein and substrate analog competitive inhibitor (chemical chaperone) form a stable complex to be transported to the lysosome, to restore the catalytic activity of mutant enzyme after spontaneous dissociation under the acidic condition. This gene mutation-specific molecular interaction is a paradoxical phenomenon that an enzyme inhibitor in vitro serves as an enzyme stabilizer in situ. First we developed a commercially available compound 1-deoxygalactonojirimycin (DGJ) for Fabry disease, and confirmed the above molecular phenomenon. Currently DGJ has become a new candidate of oral medicine for Fabry disease, generalized vasculopathy involving the kidneys, heart and central nervous system in the middle age. This drug development has reached the phase 3 of human clinical study. Then we found two valienamine derivatives, N-octyl-4-epi-?-valienamine (NOEV) and N-octyl-?-valienamine (NOV), as promising therapeutic agents for human ?-galactosidase deficiency disorders (GM1-gangliosidosis and Morquio B disease) and ?-glucosidase deficiency disorders (phenotypic variations of Gaucher disease), respectively. Originally NOEV and NOV had been discovered as competitive inhibitors, and then their paradoxical bioactivities as chaperones were confirmed in cultured fibroblasts from patients with these disorders. Subsequently GM1-gangliosidosis model mice have been used for confirmation of clinical effectiveness, adverse effects and pharmacokinetic studies. Orally administered NOEV entered the brain through the blood-brain barrier, enhanced ?-galactosidase activity, reduced substrate storage, and improved neurological deterioration clinically. Computational analysis revealed pH-dependent enzyme-chaperone interactions. Our recent study indicated chaperone activity of a new DGJ derivative, MTD118, for ?-galactosidase complementary to NOEV. NOV also showed the chaperone effect toward several ?-glucosidase gene mutants in Gaucher disease. Furthermore a commercial expectorant drug ambroxol was found to be a chaperone for ?-glucosidase. A few Gaucher patients responded to this drug with remarkable improvement of oculomotor dysfunction and myoclonus. We hope chaperone therapy will become available for some patients with Fabry disease, GM1-gangliosidosis, Gaucher disease, and other lysosomal storage diseases particularly with central nervous system involvement. PMID:23290321

Suzuki, Yoshiyuki

2013-06-01

9

N-butyldeoxygalactonojirimycin reduces neonatal brain ganglioside content in a mouse model of GM1 gangliosidosis  

Microsoft Academic Search

GM1 gangliosidosis is a glycosphingolipid (GSL) lysosomal storage disease caused by a genetic deficiency of acid b-galactosidase (b-gal), the enzyme that catabolyzes GM1 within lysosomes. Accumulation of GM1 and its asialo form (GA1) occurs primarily in the brain, leading to progressive neurodegeneration and brain dysfunction. Substrate reduction therapy aims to decrease the rate of GSL biosynthesis to counterbalance the impaired

Julie L. Kasperzyk; Mohga M. El-Abbadi; Eric C. Hauser; Alessandra d'Azzo; Frances M. Platt; Thomas N. Seyfried

2004-01-01

10

Maternal uniparental isodisomy causing autosomal recessive GM1 gangliosidosis: a clinical report.  

PubMed

Uniparental disomy is a genetic cause of disease that may result in the inheritance of an autosomal recessive condition. A child with developmental delay and hypotonia was seen and found to have severely abnormal myelination. Lysosomal enzyme testing identified an isolated deficiency of beta-galactosidase. Subsequently, homozygous missense mutations in the galactosidase, beta 1 (GLB1) gene on chromosome 3 were found. Parental testing confirmed inheritance of two copies of the same mutated maternal GLB1 gene, and no paternal copy. SNP analysis was also done to confirm paternity. The patient was ultimately diagnosed with autosomal recessive GM1 gangliosidosis caused by maternal uniparental isodisomy. We provide a review of this patient and others in which uniparental disomy (UPD) of a non-imprinted chromosome unexpectedly caused an autosomal recessive condition. This is the first case of GM1 gangliosidosis reported in the literature to have been caused by UPD. It is important for genetic counselors and other health care providers to be aware of the possibility of autosomal recessive disease caused by UPD. UPD as a cause of autosomal recessive disease drastically changes the recurrence risk for families, and discussions surrounding UPD can be complex. Working with families to understand UPD when it occurs requires a secure and trusting counselor-family relationship. PMID:24777551

King, Jessica E; Dexter, Amy; Gadi, Inder; Zvereff, Val; Martin, Meaghan; Bloom, Miriam; Vanderver, Adeline; Pizzino, Amy; Schmidt, Johanna L

2014-10-01

11

Beneficial effects of substrate reduction therapy in a mouse model of GM1 gangliosidosis  

Microsoft Academic Search

GM1 gangliosidosis is an inherited neurodegenerative disorder caused by lysosomal ?-galactosidase deficiency, resulting in the storage of GM1 and GA1, primarily in the central nervous system. This disease typically afflicts infants and young children and there is currently no effective therapy. Substrate reduction therapy (SRT) could be of potential benefit.The imino sugars N-butyldeoxynojirimycin (NB-DNJ, miglustat, Zavesca™) and N-butyldeoxygalactonojirimycin (NB-DGJ) used

Elena Elliot-Smith; Anneliese O. Speak; Emyr Lloyd-Evans; David A. Smith; Aarnoud C. van der Spoel; Mylvaganam Jeyakumar; Terry D. Butters; Raymond A. Dwek; Alessandra d’Azzo; Frances M. Platt

2008-01-01

12

Myelin Abnormalities in the Optic and Sciatic Nerves in Mice With GM1-Gangliosidosis  

PubMed Central

GM1-gangliosidosis is a glycosphingolipid lysosomal storage disease involving accumulation of GM1 and its asialo form (GA1) primarily in the brain. Thin-layer chromatography and X-ray diffraction were used to analyze the lipid content/composition and the myelin structure of the optic and sciatic nerves from 7- and 10-month old ?-galactosidase (?-gal) +/? and ?-gal ?/? mice, a model of GM1gangliosidosis. Optic nerve weight was lower in the ?-gal ?/? mice than in unaffected ?-gal +/? mice, but no difference was seen in sciatic nerve weight. The levels of GM1 and GA1 were significantly increased in both the optic nerve and sciatic nerve of the ?-gal ?/? mice. The content of myelin-enriched cerebrosides, sulfatides, and plasmalogen ethanolamines was significantly lower in optic nerve of ?-gal ?/? mice than in ?-gal +/? mice; however, cholesteryl esters were enriched in the ?-gal ?/? mice. No major abnormalities in these lipids were detected in the sciatic nerve of the ?-gal ?/? mice. The abnormalities in GM1 and myelin lipids in optic nerve of ?-gal ?/? mice correlated with a reduction in the relative amount of myelin and periodicity in fresh nerve. By contrast, the relative amount of myelin and periodicity in the sciatic nerves from control and ?-gal ?/? mice were indistinguishable, suggesting minimal pathological involvement in sciatic nerve. Our results indicate that the greater neurochemical pathology observed in the optic nerve than in the sciatic nerve of ?-gal ?/? mice is likely due to the greater glycolipid storage in optic nerve. PMID:25694553

Heinecke, Karie A.; Luoma, Adrienne; d’Azzo, Alessandra; Kirschner, Daniel A.

2015-01-01

13

GM1-gangliosidosis in American black bears: clinical, pathological, biochemical and molecular genetic characterization.  

PubMed

G(M1)-gangliosidosis is a rare progressive neurodegenerative disorder due to an autosomal recessively inherited deficiency of lysosomal ?-galactosidase. We have identified seven American black bears (Ursus americanus) found in the Northeast United States suffering from G(M1)-gangliosidosis. This report describes the clinical features, brain MRI, and morphologic, biochemical and molecular genetic findings in the affected bears. Brain lipids were compared with those in the brain of a G(M1)-mouse. The bears presented at ages 10-14 months in poor clinical condition, lethargic, tremulous and ataxic. They continued to decline and were humanely euthanized. The T(2)-weighted MR images of the brain of one bear disclosed white matter hyperintensity. Morphological studies of the brain from five of the bears revealed enlarged neurons with foamy cytoplasm containing granules. Axonal spheroids were present in white matter. Electron microscopic examination revealed lamellated membrane structures within neurons. Cytoplasmic vacuoles were found in the liver, kidneys and chondrocytes and foamy macrophages within the lungs. Acid ?-galactosidase activity in cultured skin fibroblasts was only 1-2% of control values. In the brain, ganglioside-bound sialic acid was increased more than 2-fold with G(M1)-ganglioside predominating. G(A1) content was also increased whereas cerebrosides and sulfatides were markedly decreased. The distribution of gangliosides was similar to that in the G(M1)-mouse brain, but the loss of myelin lipids was greater in the brain of the affected bear than in the brain of the G(M1) mouse. Isolated full-length cDNA of the black bear GLB1 gene revealed 86% homology to its human counterpart in nucleotide sequence and 82% in amino acid sequence. GLB1 cDNA from liver tissue of an affected bear contained a homozygous recessive T(1042) to C transition inducing a Tyr348 to His mutation (Y348H) within a highly conserved region of the GLB1 gene. The coincidence of several black bears with G(M1)-gangliosidosis in the same geographic area suggests increased frequency of a founder mutation in this animal population. PMID:24581871

Muthupalani, Sureshkumar; Torres, Paola A; Wang, Betty C; Zeng, Bai Jin; Eaton, Samuel; Erdelyi, Ildiko; Ducore, Rebecca; Maganti, Rajanikarath; Keating, John; Perry, Bain J; Tseng, Florina S; Waliszewski, Nicole; Pokras, Mark; Causey, Robert; Seger, Rita; March, Philip; Tidwell, Amy; Pfannl, Rolf; Seyfried, Thomas; Kolodny, Edwin H; Alroy, Joseph

2014-04-01

14

Exome sequencing as a diagnostic tool in a case of undiagnosed juvenile-onset GM1-gangliosidosis  

PubMed Central

Objective: To utilize high-throughput sequencing to determine the etiology of juvenile-onset neurodegeneration in a 19-year-old woman with progressive motor and cognitive decline. Methods: Exome sequencing identified an initial list of 133,555 variants in the proband's family, which were filtered using segregation analysis, presence in dbSNP, and an empirically derived gene exclusion list. The filtered list comprised 52 genes: 21 homozygous variants and 31 compound heterozygous variants. These variants were subsequently scrutinized with predicted pathogenicity programs and for association with appropriate clinical syndromes. Results: Exome sequencing data identified 2 GLB1 variants (c.602G>A, p.R201H; c.785G>T, p.G262V). ?-Galactosidase enzyme analysis prior to our evaluation was reported as normal; however, subsequent testing was consistent with juvenile-onset GM1-gangliosidosis. Urine oligosaccharide analysis was positive for multiple oligosaccharides with terminal galactose residues. Conclusions: We describe a patient with juvenile-onset neurodegeneration that had eluded diagnosis for over a decade. GM1-gangliosidosis had previously been excluded from consideration, but was subsequently identified as the correct diagnosis using exome sequencing. Exome sequencing can evaluate genes not previously associated with neurodegeneration, as well as most known neurodegeneration-associated genes. Our results demonstrate the utility of “agnostic” exome sequencing to evaluate patients with undiagnosed disorders, without prejudice from prior testing results. PMID:22675082

Adams, David A.; Markello, Thomas; Golas, Gretchen; Yang, Sandra; Sincan, Murat; Simeonov, Dimitre R.; Fuentes Fajardo, Karin; Hansen, Nancy F.; Cherukuri, Praveen F.; Cruz, Pedro; Teer, Jamie K.; Mullikin, James C.; Boerkoel, Cornelius F.; Gahl, William A.; Tifft, Cynthia J.

2012-01-01

15

AAV-Mediated Gene Delivery in Adult GM1-Gangliosidosis Mice Corrects Lysosomal Storage in CNS and Improves Survival  

PubMed Central

Background GM1-gangliosidosis is a glycosphingolipid (GSL) lysosomal storage disease caused by a genetic deficiency of acid ?-galactosidase (?gal), which results in the accumulation of GM1-ganglioside and its asialo-form (GA1) primarily in the CNS. Age of onset ranges from infancy to adulthood, and excessive ganglioside accumulation produces progressive neurodegeneration and psychomotor retardation in humans. Currently, there are no effective therapies for the treatment of GM1-gangliosidosis. Methodology/Principal Findings In this study we examined the effect of thalamic infusion of AAV2/1-?gal vector in adult GM1 mice on enzyme distribution, activity, and GSL content in the CNS, motor behavior, and survival. Six to eight week-old GM1 mice received bilateral injections of AAV vector in the thalamus, or thalamus and deep cerebellar nuclei (DCN) with pre-determined endpoints at 1 and 4 months post-injection, and the humane endpoint, or 52 weeks of age. Enzyme activity was elevated throughout the CNS of AAV-treated GM1 mice and GSL storage nearly normalized in most structures analyzed, except in the spinal cord which showed ?50% reduction compared to age-matched untreated GM1 mice spinal cord. Survival was significantly longer in AAV-treated GM1 mice (52 wks) than in untreated mice. However the motor performance of AAV-treated GM1 mice declined over time at a rate similar to that observed in untreated GM1 mice. Conclusions/Significance Our studies show that the AAV-modified thalamus can be used as a ‘built-in’ central node network for widespread distribution of lysosomal enzymes in the mouse cerebrum. In addition, this study indicates that thalamic delivery of AAV vectors should be combined with additional targets to supply the cerebellum and spinal cord with therapeutic levels of enzyme necessary to achieve complete correction of the neurological phenotype in GM1 mice. PMID:20976108

Baek, Rena C.; Broekman, Marike L. D.; Leroy, Stanley G.; Tierney, Laryssa A.; Sandberg, Michael A.; d'Azzo, Alessandra; Seyfried, Thomas N.; Sena-Esteves, Miguel

2010-01-01

16

Evaluation of N-nonyl-deoxygalactonojirimycin as a pharmacological chaperone for human GM1 gangliosidosis leads to identification of a feline model suitable for testing enzyme enhancement therapy  

PubMed Central

Deficiencies of lysosomal ?-D-galactosidase can result in GM1 gangliosidosis, a severe neurodegenerative disease characterized by massive neuronal storage of GM1 ganglioside in the brain. Currently there are no available therapies that can even slow the progression of this disease. Enzyme enhancement therapy utilizes small molecules that can often cross the blood brain barrier, but are also often competitive inhibitors of their target enzyme. It is a promising new approach for treating diseases, often caused by missense mutations, associated with dramatically reduced levels of functionally folded enzyme. Despite a number of positive reports based on assays performed with patient cells, skepticism persists that an inhibitor-based treatment can increase mutant enzyme activity in vivo. To date no appropriate animal model, i.e., one that recapitulates a responsive human genotype and clinical phenotype, has been reported that could be used to validate enzyme enhancement therapy. In this report, we identify a novel enzyme enhancement-agent, N-nonyl-deoxygalactonojirimycin, that enhances the mutant ?-galactosidase activity in the lysosomes of a number of patient cell lines containing a variety of missense mutations. We then demonstrate that treatment of cells from a previously described, naturally occurring feline model (that biochemically, clinically and molecularly closely mimics GM1 gangliosidosis in humans) with this molecule, results in a robust enhancement of their mutant lysosomal ?-galactosidase activity. These data indicate that the feline model could be used to validate this therapeutic approach and determine the relationship between the disease stage at which this therapy is initiated and the maximum clinical benefits obtainable. PMID:22784478

Rigat, Brigitte A.; Tropak, Michael B.; Buttner, Justin; Crushell, Ellen; Benedict, Daphne; Callahan, John W.; Martin, Douglas R.; Mahuran, Don J.

2012-01-01

17

Central nervous system inflammation is a hallmark of pathogenesis in mouse models of GM1 and GM2 gangliosidosis.  

PubMed

Mouse models of the GM2 gangliosidoses [Tay-Sachs, late onset Tay-Sachs (LOTS), Sandhoff] and GM1 gangliosidosis have been studied to determine whether there is a common neuro-inflammatory component to these disorders. During the disease course, we have: (i) examined the expression of a number of inflammatory markers in the CNS, including MHC class II, CD68, CD11b (CR3), 7/4, F4/80, nitrotyrosine, CD4 and CD8; (ii) profiled cytokine production [tumour necrosis factor alpha (TNF alpha), transforming growth factor (TGF beta 1) and interleukin 1 beta (IL1 beta)]; and (iii) studied blood-brain barrier (BBB) integrity. The kinetics of apoptosis and the expression of Fas and TNF-R1 were also assessed. In all symptomatic mouse models, a progressive increase in local microglial activation/expansion and infiltration of inflammatory cells was noted. Altered BBB permeability was evident in Sandhoff and GM1 mice, but absent in LOTS mice. Progressive CNS inflammation coincided with the onset of clinical signs in these mouse models. Substrate reduction therapy in the Sandhoff mouse model slowed the rate of accumulation of glycosphingolipids in the CNS, thus delaying the onset of the inflammatory process and disease pathogenesis. These data suggest that inflammation may play an important role in the pathogenesis of the gangliosidoses. PMID:12615653

Jeyakumar, M; Thomas, R; Elliot-Smith, E; Smith, D A; van der Spoel, A C; d'Azzo, A; Perry, V Hugh; Butters, T D; Dwek, R A; Platt, F M

2003-04-01

18

Neurovisceral and Skeletal GM1Gangliosidosis in Dogs with beta Galactosidase Deficiency  

Microsoft Academic Search

beta -galactosidase-deficient siblings in two litters of English springer spaniel puppies showed a progressive neurological impairment, dwarfism, orbital hypertelorism, and dysostosis multiplex. An excess of GM1-ganglioside was found in the brain. Three abnormal oligosaccharides were present in samples of urine, brain, liver, and cartilage. Light microscopy of selected tissue specimens revealed cytoplasmic vacuoles in neurons, circulating blood cells, macrophages, and

Joseph Alroy; Uri Orgad; Angelo A. Ucci; Scott H. Schelling; Kenneth L. Schunk; Christopher D. Warren; Srinivasa S. Raghavan; Edwin H. Kolodny

1985-01-01

19

Central nervous system inflammation is a hallmark of pathogenesis in mouse models of GM1 and GM2 gangliosidosis  

Microsoft Academic Search

Summary Mouse models of the GM2 gangliosidoses (Tay-Sachs, late onset Tay-Sachs (LOTS), Sandhoff) and GM1 gang- liosidosis have been studied to determine whether there is a common neuro-inflammatory component to these disorders. During the disease course, we have: (i) exam- ined the expression of a number of inflammatory mark- ers in the CNS, including MHC class II, CD68, CD11b (CR3),

M. Jeyakumar; R. Thomas; E. Elliot-Smith; D. A. Smith; A. C. van der Spoel; A. d'Azzo; V. Hugh Perry; T. D. Butters; R. A. Dwek; F. M. Platt

2003-01-01

20

Isolation and characterization of the normal canine beta-galactosidase gene and its mutation in a dog model of GM1-gangliosidosis.  

PubMed

The acid beta-galactosidase cDNA of Portuguese Water dogs was isolated and sequenced. The entire coding region of the gene consists of 2004 nucleotides encoding a protein of 668 amino acids. Its encoding sequence indicates approximately 86.5% identity at the nucleotide level and about 81% identity at the amino acid level with the encoding region of the human acid beta-galactosidase gene. The deduced amino acid sequence contains a 24-amino-acid putative signal sequence, six possible glycosylation sites, and seven cysteine residues. A homozygous recessive mutation, causing canine GM1-gangliosidosis, was identified at nucleotide G200-->A in exon 2 resulting in an Arg60-->His (mutation R60H) amino acid substitution. The mutation creates a new restriction enzyme site for Pml1. Genotyping 115 dog samples for this acid beta-galactosidase gene alteration readily distinguished affected homozygous recessives (n=5), heterozygous carriers (n=50) and normal homozygotes (n=60). DNA mutation analysis provided a method more specific than enzyme assay of beta-galactosidase for determination of carriers. PMID:11032334

Wang, Z H; Zeng, B; Shibuya, H; Johnson, G S; Alroy, J; Pastores, G M; Raghavan, S; Kolodny, E H

2000-09-01

21

Generalized Gangliosidosis: Beta-Galactosidase Deficiency  

Microsoft Academic Search

A profound deficiency (10- to 30-fold) of beta -galactosidase activity was found in tissues (liver, spleen, kidney, and brain) from two patients with generalized gangliosidosis; this deficiency is demonstrated as a failure to cleave both p-nitrophenyl-beta -D-galactopyranoside and ganglioside GM1 labeled with C14 in the terminal galactose. We believe that this enzymic defect is responsible for the accumulation of ganglioside

Shintaro Okada; John S. O'Brien

1968-01-01

22

Impaired sulphated glycosaminoglycan metabolism in a patient with GM2 gangliosidosis (Tay-Sachs disease)  

Microsoft Academic Search

Summary An abnormal urinary excretion of sulphated glycosaminoglycans in a patient with GM-2 gangliosidosis (Tay-Sachs disease) is described. Besides the accumulation of GM-2 ganglioside in liver and lack of hexosaminidase A, the patient shows an abnormal urinary excretion of an iduronic acid-rich low molecular weight heparan sulphate. Also, no dermatan sulphate could be detected in the urine, whereas this compound

L. Toma; W. Pinto; V. C. Rodrigues; C. P. Dietrich; H. B. Nader

1990-01-01

23

Genetics Home Reference: GM1 gangliosidosis  

MedlinePLUS

... retina) gradually deteriorates. An eye abnormality called a cherry-red spot, which can be identified with an ... experience developmental regression but usually do not have cherry-red spots, distinctive facial features, or enlarged organs. ...

24

Pharmacokinetics, safety and tolerability of miglustat in the treatment of pediatric patients with GM2 gangliosidosis  

Microsoft Academic Search

GM2 gangliosidosis (GM2g) is an inherited neurodegenerative disorder caused by deficiency of lysosomal ?-hexosaminidase A, resulting in accumulation of GM2 ganglioside, principally in the brain. Substrate reduction therapy is currently under investigation as a treatment. The study investigated the pharmacokinetics and safety of miglustat given as single and multiple doses in infantile and juvenile GM2g patients for 6- and 24-months,

Gustavo H. B. Maegawa; Paul L. M. van Giersbergen; Sandra Yang; Brenda Banwell; Christopher P. Morgan; Jasper Dingemanse; Cynthia J. Tifft; Joe T. R. Clarke

2009-01-01

25

Mutations in acid [beta]-galactosidase cause GM[sub 1]-gangliosidosis in American patients  

SciTech Connect

The authors describe four new mutations in the [beta]-galactosidase gene. These are the first mutations causing infantile and juvenile GM[sub 1]-gangliosidosis to be described in American patients. Cell lines from two patients with juvenile and from six patients with infantile GM[sub 1]-gangliosidosis were analyzed. Northern blot analysis showed the acid [beta]-galactosidase message to be of normal size and quantity in two juvenile and four infantile cases and of normal size but reduced quantity in two infantile cases. The mutations are distinct from the Japanese mutations. All are point mutations leading to amino acid substitutions: Lys[sup 577] [yields] Arg, Arg[sup 590] [yields] His, and Glu[sup 632] [yields] Gly. The fourth mutation, Arg[sup 208] [yields] Cys, accounts for 10 of 16 possible alleles. Two infantile cases from Puerto Rico of Spanish ancestry are homozygous for this mutation, suggesting that this allele may have come to South America and North America via Puerto Rico. That these mutations cause clinical disease was confirmed by marked reduction in catalytic activity of the mutant proteins in the Cos-1 cell expression system. 12 refs., 5 figs., 2 tabs.

Boustany, R.M.; Qian, W.H. (Duke Univ., Durham, NC (United States)); Suzuki, K. (Univ. of North Carolina, Chapel Hill, NC (United States))

1993-10-01

26

Ganglioside-monosialic acid (GM1) prevents oxaliplatin-induced peripheral neurotoxicity in patients with gastrointestinal tumors  

PubMed Central

Background Oxaliplatin, an effective antineoplastic agent againstgastrointestinal tumors, can cause severe peripheral neurotoxicity, which seriously limits its clinical application. To date, there are no effective treatments for this complication. Ganglioside-monosialic acid (GM1) has been shown to protect neurons against injuries and degeneration. The aim of this study was to evaluate the effects of GM1 on preventing oxaliplatin-induced neurotoxicity in patients with gastrointestinal tumors. Methods In this study, 120 patients with gastrointestinal tumors were enrolled, andthey received the treatment of XELOX (oxaliplatin and capecitabine) and FOLFOX4 (oxaliplatin, leukovolin and 5-fluorouracil). The patients were randomly divided into two groups, the experimental group and control group, with60 patients ineach. On the day chemotherapy was initiated, the experimental group received GM1 intravenously (100 mg once daily) for 3 days, while no neuroprotective agents were applied in the control group. The incidence rates and classification of neurotoxicity in the two groups were evaluated and the differences between the two groups were examined. Furthermore, whether GM1 affected the therapeutic effects of chemotherapy was also examined. Results The grade of neurotoxicity in the experimental group was significantly lower than in the control group (P<0.05, Mann–Whitney U test). The probability of occurrence of low-grade neurotoxicity (grade 0 and 1) in the experimental group was higher than that in the control group (logistic ordinal regression); whereas the probability of occurrence of high-grade neurotoxicity (grade 2 and 3) in the experimental group was lower than in the control group (logistic ordinal regression). Conclusion The data suggested that GM1 could reduce the grade of oxaliplatin-induced neurotoxicity and was an effective neuroprotective agent against oxaliplatin-induced high-grade neurotoxicity in patients with gastrointestinal tumors. PMID:23351188

2013-01-01

27

Immunogenicity of a fucosyl-GM1-keyhole limpet hemocyanin conjugate vaccine in patients with small cell lung cancer.  

PubMed

Although small cell lung cancer (SCLC) is highly responsive to chemotherapy, relapses are common, and most patients die within 2 years of diagnosis. After initial therapy, standard treatment is observation alone. We have been investigating immunization against selected gangliosides as adjuvant therapy directed against residual and presumably resistant disease persisting after chemotherapy and irradiation. Previously, we reported that the presence of anti-GM2 ganglioside antibodies is associated with a prolonged disease-free survival in patients with melanoma, and that SCLC patients immunized with BEC2, an anti-idiotypic monoclonal antibody that mimics the ganglioside GD3, had a prolonged survival compared with historical controls. In the present trial, fucosyl-alpha1-2Galbeta1-3GalNAcbeta1-4(NeuAcalpha2-3) Galbeta1-4Glcbeta1-1Cer (Fuc-GM1), a ganglioside expressed on the SCLC cell surface, was selected as a target for active immunotherapy. Fuc-GM1 is present on most SCLCs but on few normal tissues. SCLC patients achieving a major response to initial therapy were vaccinated s.c. on weeks 1, 2, 3, 4, 8, and 16 with Fuc-GM1 (30 microg) conjugated to the carrier protein keyhole limpet hemocyanin and mixed with the adjuvant QS-21. Ten patients received at least five vaccinations and are evaluable for response. All patients demonstrated a serological response, with induction of both IgM and IgG antibodies against Fuc-GM1, despite prior treatment with chemotherapy with or without radiation. Posttreatment flow cytometry demonstrated binding of antibodies from patients' sera to tumor cells expressing Fuc-GM1. In the majority of cases, sera were also capable of complement-mediated cytotoxicity. Mild transient erythema and induration at injection sites were the only consistent toxicities. The Fuc-GM1-KLH + QS-21 vaccine is safe and immunogenic in patients with SCLC. Continued study of this and other ganglioside vaccines is ongoing. PMID:10537341

Dickler, M N; Ragupathi, G; Liu, N X; Musselli, C; Martino, D J; Miller, V A; Kris, M G; Brezicka, F T; Livingston, P O; Grant, S C

1999-10-01

28

The AB-variant of GM2-gangliosidosis. Clinical, biochemical, and pathological studies of two patients.  

PubMed

Clinical, neuropathological, and biochemical studies are reported in two children with the AB-variant of GM2-gangliosidosis. One patient had become symptomatic by 1--1.5 years, initially showing cerebellar signs, and then progressive psychomotor retardation, with hypotonia, spasticity, dementia, and macular cherry red spots, until death at the age of 4.5 years. The second patient showed an earlier onset of retardation and a more rapidly progressive course. At postmortem, the brains were of normal or near normal weights and displayed grossly only mild cerebral cortical and cerebellar atrophy, and mild pallor or attenuation of the white matter. Neuronal storage was widespread throughout the CNS, and both neurons and glia contained a variety of abnormal, membranous inclusions. Visceral organs were not involved. Ganglioside sialic acid was increased several fold in gray matter, with GM2 the predominant ganglioside species. N-acetyl-beta-glucosaminidase activities in serum, leukocytes, fibroblasts, and postmortem gray matter, assayed with an artificial, fluorogenic substrate, were normal, as were activities of other lysosomal hydrolases. PMID:6255724

Goldman, J E; Yamanaka, T; Rapin, I; Adachi, M; Suzuki, K; Suzuki, K

1980-01-01

29

Complex of GM1- and GD1a-Like Lipo-Oligosaccharide Mimics GM1b, Inducing Anti-GM1b Antibodies  

PubMed Central

Objective Molecular mimicry between Campylobacter jejuni lipo-oligosaccharides (LOSs) and human gangliosides GM1 and GD1a induces the production of anti-GM1 and anti-GD1a antibodies, and the development of Guillain-Barré syndrome. Complexes of two different gangliosides form new molecular shapes capable of enhancing recognition by anti-ganglioside antibodies. To test the hypothesis that the complex of GM1-like and GD1a-like LOSs of C. jejuni induces the development of anti-GM1b antibodies in Guillain-Barré syndrome patients. Methods Mass spectrometry analysis determined the LOS outer core structures, with which mice were immunized. IgG antibodies to single gangliosides and complex of gangliosides were tested in sera from Guillain-Barré syndrome patients from whom C. jejuni LOS had been isolated. Results Two isolates from GBS patients who had anti-GM1b antibodies, but neither anti-GM1 nor -GD1a antibodies, expressed both GM1-like and GD1a-like LOSs, but not GM1b-like LOS. Anti-GM1b antibodies were induced in one of the mice immunized with the C. jejuni bearing GM1-like and GD1a-like LOS. Sera from 20 patients had antibodies to the complex of GM1 and GD1a, all of which carried anti-GM1b reactivity. Five of these sera harbored neither anti-GM1 nor anti-GD1a antibodies. IgG antibodies to the complex were absorbed by GM1b, but by neither GM1 nor GD1a. Conclusions GM1-like and GD1a-like LOSs form a GM1b epitope, inducing the development of anti-GM1b antibodies in patients with Guillain-Barré syndrome subsequent to C. jejuni enteritis. Here, we present a new paradigm that the complex of two different structures forms a new molecular mimicry, inducing the production of autoantibodies. PMID:25867522

Koga, Michiaki; Gilbert, Michel; Li, Jianjun; Yuki, Nobuhiro

2015-01-01

30

Two new human {beta}-galactosidase gene mutations in American patients with slowly progressive G{sub M1} gangliosidosis  

SciTech Connect

Two cases with slowly progressive forms of G{sub M1} gangliosidosis were each found to have a novel mutation for the {beta}-galactosidase gene. AS (died at 4 yr) began with symptoms at 8 months ({beta}-galactosidase activity 10% normal) and HS (59 yr) developed dystronic hand movements at age 3 yr ({beta}-galactosidase activity < 2% of normal controls). The entire 2.4 coding region was sequenced in both directions for each patient using RT-PCR. First strand cDNA was synthesized from fibroblast RNA and double stranded PCR fragments spanning the coding region were made with oligonucleotide primers. Sequencing was performed using asymmetric PCR products made from each double stranded product. Case AS was found to have a nine base-pair insertion [CAGAATTTT] on one allele beginning at nucleotide position 730, which did not result in a frameshift and is predicted to cause the insertion of three amino acids (Glu-Phe-Ser) between amino acids 44-45. No other mutations in the coding region were identified on this or the other allele in this individual. Case HS had a unique point mutation identified in one allele. This mutation was an A{r_arrow}G transition at nucleotide 797 which results in a Asn{r_arrow}Ser amino acid substitution in codon 266 (mutation N266S) with no other mutations found in the expressed RNA sequences. SSCP was performed on a 200 bp region surrounding codon 266 using genomic DNA from over 50 controls to look for changes in nucleotide sequence. Only case HS demonstrated a shift indicating that the base pair change did not represent a normal polymorphism.

Shalish, C.; Breakefield, X.O. [Massachusetts General Hospital, Boston, MA (United States); Kaye, E.M. [Tufts Univ. School of Medicine, Boston, MA (United States)] [and others

1994-09-01

31

Genetics Home Reference: GM2-gangliosidosis, AB variant  

MedlinePLUS

... Patients and Families Resources for Health Professionals What glossary definitions help with understanding GM2-gangliosidosis, AB variant? ... many other terms in the Genetics Home Reference Glossary . See also Understanding Medical Terminology . References (4 links) ...

32

High levels of GM(1)-ganglioside and GM(1)-ganglioside beta-galactosidase in the parotid gland: a new model for secretory mechanisms of the parotid gland.  

PubMed

A new model for the subcellular basis of parotid secretion is presented in this article. GM(1)-ganglioside, typically found in neural tissues, is shown to be abundant in the parotid gland. This ganglioside may play a central role in membrane turnover mechanisms underlying exocytosis/endocytosis in its role as a promoter of membrane fusion or a fusogen. The lysosome and lysosomal hydrolases also play a central role in this model in catabolism of GM(1)-ganglioside. Consequently, high levels of the lysosomal hydrolase acidic beta-galactosidase are demonstrated in the salivary gland. GM(1)-gangliosidosis of the parotid glands, as described in mice, appears to be the first single-gene heritable disease found so far in the salivary glands. PMID:10477786

Nowroozi, N; Kim, S; Segawa, A; Warita, H; Rice, D H; Denny, P C; Zernik, J H

1999-10-01

33

Biochemical and molecular characterization of novel mutations in GLB1 and NEU1 in patient cells with lysosomal storage disorders.  

PubMed

Lysosomes are cytoplasmic compartments that contain many acid hydrolases and play critical roles in the metabolism of a wide range of macromolecules. Deficiencies in lysosomal enzyme activities cause genetic diseases, called lysosomal storage disorders (LSDs). Many mutations have been identified in the genes responsible for LSDs, and the identification of mutations is required for the accurate molecular diagnoses. Here, we analyzed cell lines that were derived from two different LSDs, GM1 gangliosidosis and sialidosis. GM1 gangliosidosis is caused by mutations in the GLB1 gene that encodes ?-galactosidase. A lack of ?-galactosidase activity leads to the massive accumulation of GM1 ganglioside, which results in neurodegenerative pathology. Mutations in the NEU1 gene that encodes lysosomal sialidase cause sialidosis. Insufficient activity of lysosomal sialidase progressively increases the accumulation of sialylated molecules, and various clinical symptoms, including mental retardation, appear. We sequenced the entire coding regions of GLB1 and NEU1 in GM1 gangliosidosis and sialidosis patient cells, respectively. We found the novel mutations p.E186A in GLB1 and p.R347Q in NEU1, as well as many other mutations that have been previously reported. We also demonstrated that patient cells containing the novel mutations showed the molecular phenotypes of the corresponding disease. Further structural analysis suggested that these novel mutation sites are highly conserved and important for enzyme activity. PMID:25600812

Kwak, Jae Eun; Son, Mi-Young; Son, Ye Seul; Son, Myung Jin; Cho, Yee Sook

2015-02-20

34

Establishment of monoclonal antibodies specific for ganglioside GM1: detection of ganglioside GM1 in small cell lung carcinoma cell lines and tissues.  

PubMed

Three kinds of anti-GM1 monoclonal antibodies, AGM-1, -2, and -3, of the IgM class were produced by the immunization of BALB/c mice with ganglioside GM1 inserted into liposomes with Salmonella minnesota R595 lipopolysaccharides and fusion of the spleen cells with a mouse myeloma cell line. The specificities of the monoclonal antibodies obtained were elucidated through complement-dependent liposome immune lysis assay and enzyme immunostaining on thin-layer chromatograms. All of the monoclonal antibodies reacted only with ganglioside GM1, and structurally related glycosphingolipids, such as fucosyl-GM1, asialo-GM1, GM2, and GD1b, and the other gangliosides (GM3 and GD1a) tested showed no reactivity to the 3 monoclonal antibodies. These findings suggest that the monoclonal antibodies obtained may be specific for ganglioside GM1. These anti-GM1 monoclonal antibodies were used to define the expression of ganglioside GM1 on small cell lung carcinoma (SCLC) cell lines and tissues. In flow cytometric analysis and immunostaining studies, we observed that ganglioside GM1 was highly expressed on the SCLC cell lines. Results obtained with flow cytometry and immunohistochemistry agreed well with the immunochemical determination of ganglioside GM1 in lipid extracts of cell lines. Furthermore, expression of ganglioside GM1 in tumor tissues from patients with SCLC was ascertained by the immunohistochemical examination of acetone-fixed paraffin-embedded tissue sections. Ganglioside GM1 was detected in 5 of 19 SCLC tissues. These results suggest that ganglioside GM1 is expressed in SCLC cells. PMID:7896755

Watarai, S; Kiura, K; Shigeto, R; Shibayama, T; Kimura, I; Yasuda, T

1994-11-01

35

Gene Transfer to Human Cells: Transducing Phage lambda plac Gene Expression in GMI-gangliosidosis Fibroblasts  

Microsoft Academic Search

Genetic information from the bacterium Escherichia coli was transferred to human cells by means of the specialized transducing phage lambda plac carrying the bacterial z gene for the enzyme beta -galactosidase (beta -D-galactoside galactohydrolase, EC 3.2.1.23). As recipient cells, cultured skin fibroblasts from a patient with generalized gangliosidosis (GMI-gangliosidosis Type I) characterized by a severe deficiency of beta -galactosidase activity

Jurgen Horst; Friedrich Kluge; Konrad Beyreuther; Wolfgang Gerok

1975-01-01

36

An open-label Phase I/II clinical trial of pyrimethamine for the treatment of patients affected with chronic GM2 gangliosidosis (Tay-Sachs or Sandhoff variants).  

PubMed

Late-onset GM2 gangliosidosis is an autosomal recessive, neurodegenerative, lysosomal storage disease, caused by deficiency of ß-hexosaminidase A (Hex A), resulting from mutations in the HEXA (Tay-Sachs variant) or the HEXB (Sandhoff variant) genes. The enzyme deficiency in many patients with juvenile or adult onset forms of the disease results from the production of an unstable protein, which becomes targeted for premature degradation by the quality control system of the smooth endoplasmic reticulum and is not transported to lysosomes. In vitro studies have shown that many mutations in either the ? or ? subunit of Hex A can be partially rescued, i.e. enhanced levels of both enzyme protein and activity in lysosomes, following the growth of patient cells in the presence of the drug, pyrimethamine. The objectives of the present clinical trial were to establish the tolerability and efficacy of the treatment of late-onset GM2 gangliosidosis patients with escalating doses of pyrimethamine, to a maximum of 100 mg per day, administered orally in a single daily dose, over a 16-week period . The primary objective, tolerability, was assessed by regular clinical examinations, along with a panel of hematologic and biochemical studies. Although clinical efficacy could not be assessed in this short trial, treatment efficacy was evaluated by repeated measurements of leukocyte Hex A activity, expressed relative to the activity of lysosomal ß-glucuronidase. A total of 11 patients were enrolled, 8 males and 3 females, aged 23 to 50 years. One subject failed the initial screen, another was omitted from analysis because of the large number of protocol violations, and a third was withdrawn very early as a result of adverse events which were not drug-related. For the remaining 8 subjects, up to a 4-fold enhancement of Hex A activity at doses of 50 mg per day or less was observed. Additionally marked individual variations in the pharmacokinetics of the drug among the patients were noted. However, the study also found that significant side effects were experienced by most patients at or above 75 mg pyrimethamine per day. We concluded that pyrimethamine treatment enhances leukocyte Hex A activity in patients with late-onset GM2 gangliosidosis at doses lower than those associated with unacceptable side effects. Further plans are underway to extend these trials and to develop methods to assess clinical efficacy. PMID:20926324

Clarke, Joe T R; Mahuran, Don J; Sathe, Swati; Kolodny, Edwin H; Rigat, Brigitte A; Raiman, Julian A; Tropak, Michael B

2011-01-01

37

Mutations in the lysosomal [beta]-galactosidase gene that cause the adult form of GMI gangliosidosis  

SciTech Connect

Three adult patients with acid-galactosidase deficiency/GM1 gangliosidosis who were from two unrelated families of Scandinavian descent were found to share a common point mutation in the coding region of the corresponding gene. The patients share common clinical features, including early dysarthria, mild ataxia, and bone abnormalities. When cDNA from the two patients in family 1 was PCR amplified and sequenced, most (39/41) of the clones showed a C-to-T transition (C[yields]T) at nucleotide 245 (counting from the initiation codon). This mutation changes the codon for the Thr(ACG) to Met(ATG). Mutant and normal sequences were also found in that position in genomic DNA, indicating the presence of another mutant allele. Genomic DNA from the patient in family 2 revealed the same point mutation in one allele. It was determined that in each family only the father carried the C[yields]T mutation. Expression studies showed that this mutation produced 3%-4% of [beta]-galactosidase activity, confirming its deleterious effects. The cDNA clones from the patients in family 1 that did not contain the C[yields]T revealed a 20-bp insertion of intronic sequence between nucleotides 75 and 76, the location of the first intron. Further analysis showed the insertion of a T near the 5[prime] splice donor site which led to the use of a cryptic splice site. It appears that the C[yields]T mutation results in enough functional enzyme to produce a mild adult form of the disease, even in the presence of a second mutation that likely produces nonfunctional enzyme. 31 refs., 7 figs., 1 tab.

Chakraborty, S.; Rafi, M.A.; Wenger, D.A. (Thomas Jefferson Univ., Philadelphia, PA (United States))

1994-06-01

38

Substrate reduction therapy in juvenile GM2 gangliosidosis  

Microsoft Academic Search

Substrate reduction therapy (SRT) is considered to be a potential therapeutic option for juvenile GM2 gangliosidosis (jGM2g). We evaluated the efficacy of SRT in jGM2g, assessing neurological, neuropsychological and brain magnetic resonance imaging (MRI) outcomes over a 24-month period of treatment. In an open-label and single-center study, five jGM2g patients (mean age 14.6±4.5years) received oral miglustat at doses of 100–200mg

Gustavo H. B. Maegawa; Brenda L. Banwell; Susan Blaser; Geoffrey Sorge; Maggie Toplak; Cameron Ackerley; Cynthia Hawkins; Jason Hayes; Joe T. R. Clarke

2009-01-01

39

Significance of two point mutations present in each HEXB allele of patients with adult G M2 gangliosidosis (Sandhoff disease) Homozygosity for the Ile 207 ? Val substitution is not associated with a clinical or biochemical phenotype  

Microsoft Academic Search

The molecular defects in the HEXB gene encoding the common ?-subunit of lysosomal ?-hexosaminidase A (?-Hex A, ??) and ?-Hex B (??) were investigated in a Portuguese family affected with late onset Sandhoff disease (GM2-gangliosidosis variant 0). This family comprised two unaffected daughters and three affected sibs who developed at about age 17 cerebellar ataxia and mental deficiency. Their parents

Isabelle Redonnet-Vernhet; Don J. Mahuran; Robert Salvayre; Frédéric Dubas; Thierry Levade

1996-01-01

40

MR Imaging and Proton Spectroscopy of Neuronal Injury in Late-Onset GM2 Gangliosidosis  

Microsoft Academic Search

BACKGROUND AND PURPOSE: Despite the ubiquity of GM2 gangliosides accumulation in patients with late-onset GM2 gangliosidosis (GM2G), the only clinical MR imaging-apparent brain abnormality is profound cerebellar atrophy. The goal of this study was to detect the presence and assess the extent of neuroaxonal injury in the normal-appearing gray and white matter (NAGM and NAWM) of these patients. METHODS: During

Matilde Inglese; Annette O. Nusbaum; Gregory M. Pastores; John Gianutsos; Edwin H. Kolodny; Oded Gonen

41

Substrate reduction therapy with miglustat in chronic GM2 gangliosidosis type Sandhoff: results of a 3-year follow-up  

Microsoft Academic Search

GM2 gangliosidosis type Sandhoff is caused by a defect of beta-hexosaminidase, an enzyme involved in the catabolism of gangliosides.\\u000a It has been proposed that substrate reduction therapy using N-butyl-deoxynojirimycin (miglustat) may delay neurological progression,\\u000a at least in late-onset forms of GM2 gangliosidosis. We report the results of a 3-year treatment with miglustat (100 mg t.i.d)\\u000a in a patient with chronic Sandhoff

Marcella Masciullo; Massimo Santoro; Anna Modoni; Enzo Ricci; Jerome Guitton; Pietro Tonali; Gabriella Silvestri

42

Induction of anti-GM1 ganglioside antibodies by Campylobacter jejuni lipopolysaccharides.  

PubMed

A frequent association exists between acute motor neuropathy, antecedent Campylobacter jejuni (CJ) and anti-GM ganglioside antibodies. Despite the chemical and immunological similarity between CJ lipopolysaccharides (LPS) and GM1, the mechanism of induction of anti-GM1 antibodies is still unclear. We used CJ LPS to immunize rats, mice and immunodeficient mice lacking in NK, CD8+ or T-cell populations. None of these animals developed significant anti-GM1 titers. However, rats immunized with keyhole limpet hemocyanin which contains the cross-reactive sugar epitope Gal(beta1-3)GalNAc developed high titers of IgM anti-GM1 antibodies. This occurred only after these rats were given an intraperitoneal injection of CJ LPS. These results suggest that a glycoprotein antigenic stimulus can induce B-cells which are autoreactive to ganglioside but which remain anergic. A second stimulus with a cross-reactive LPS can then overcome the anergy to induce autoantibody production. A similar mechanism may explain the occurrence of GM1 antibodies in patients after CJ enteritis. PMID:9307238

Wirguin, I; Briani, C; Suturkova-Milosevic, L; Fisher, T; Della-Latta, P; Chalif, P; Latov, N

1997-09-01

43

Optimization of GM(1,1) power model  

NASA Astrophysics Data System (ADS)

GM (1,1) power model is the expansion of traditional GM (1,1) model and Grey Verhulst model. Compared with the traditional models, GM (1,1) power model has the following advantage: The power exponent in the model which best matches the actual data values can be found by certain technology. So, GM (1,1) power model can reflect nonlinear features of the data, simulate and forecast with high accuracy. It's very important to determine the best power exponent during the modeling process. In this paper, according to the GM(1,1) power model of albino equation is Bernoulli equation, through variable substitution, turning it into the GM(1,1) model of the linear albino equation form, and then through the grey differential equation properly built, established GM(1,1) power model, and parameters with pattern search method solution. Finally, we illustrate the effectiveness of the new methods with the example of simulating and forecasting the promotion rates from senior secondary schools to higher education in China.

Luo, Dang; Sun, Yu-ling; Song, Bo

2013-10-01

44

GM1 and GM2 gangliosides: recent developments.  

PubMed

GM1 and GM2 gangliosides are important components of the cell membrane and play an integral role in cell signaling and metabolism. In this conceptual overview, we discuss recent developments in our understanding of the basic biological functions of GM1 and GM2 and their involvement in several diseases. In addition to a well-established spectrum of disorders known as gangliosidoses, such as Tay-Sachs disease, more and more evidence points at an involvement of GM1 in Alzheimer's and Parkinson's diseases. New emerging methodologies spanning from single-molecule imaging in vivo to simulations in silico have complemented standard studies based on ganglioside extraction. PMID:25372744

Bisel, Blaine; Pavone, Francesco S; Calamai, Martino

2014-03-01

45

Small cell lung cancer is not associated with the presence of anti-fucosyl-GM1 ganglioside autoantibodies reactive in immunoenzymatic test.  

PubMed

The characteristic feature of small cell lung cancer carcinoma (SCLC) is the aberrant expression and abundant presentation of fucosyl-GM1 ganglioside (FucGM1). In the present study we searched for the presence of anti-FucGM1 ganglioside, as well as anti-GM1, GM2 and GD3 ganglioside autoantibodies in the sera of patients with SCLC and as a control, in sera of patients with renal cell cancer (RC) and healthy blood donors. The autoantibodies against FucGM1 were present at low titer in only three of 36 SCLC patients, and with similar titer in two of 36 RC patients and four of 36 healthy controls. Likewise, the autoantibodies against GM2 and GM3 gangliosides were found only sporadically and with the same titer and frequency in cancer patients as in healthy persons. Anti-GD3 autoantibodies could not be detected in any of the screened sera. PMID:11714535

Adler, G; Pacuszka, T; Lewartowska, A; Rowinska, E; Oblakowski, P; Panasiewicz, M

2001-12-01

46

GDNF signaling implemented by GM1 ganglioside; failure in Parkinson's disease and GM1-deficient murine model.  

PubMed

GDNF is indispensible for adult catecholaminergic neuron survival, and failure of GDNF signaling has been linked to loss of dopaminergic neurons in Parkinson's disease (PD). This study demonstrates attenuated GDNF signaling in neurons deficient in ganglio-series gangliosides, and restoration of such signaling with LIGA20, a membrane permeable analog of GM1. GM1 is shown to associate in situ with GFR?1 and RET, the protein components of the GDNF receptor, this being necessary for assembly of the tripartite receptor complex. Mice wholly or partially deficient in GM1 due to disruption of the B4galnt1 gene developed PD symptoms based on behavioral and neuropathological criteria which were largely ameliorated by gene therapy with AAV2-GDNF and also with LIGA20 treatment. The nigral neurons of PD subjects that were severely deficient in GM1 showed subnormal levels of tyrosine phosphorylated RET. Also in PD brain, GM1 levels in the occipital cortex, a region of limited PD pathology, were significantly below age-matched controls, suggesting the possibility of systemic GM1 deficiency as a risk factor in PD. This would accord with our finding that mice with partial GM1 deficiency represent a faithful recapitulation of the human disease. Together with the previously demonstrated age-related decline of GM1 in human brain, this points to gradual development of subthreshold levels of GM1 in the brain of PD subjects below that required for effective GDNF signaling. This hypothesis offers a dramatically different explanation for the etiology of sporadic PD as a manifestation of acquired resistance to GDNF. PMID:25448159

Hadaczek, Piotr; Wu, Gusheng; Sharma, Nitasha; Ciesielska, Agnieszka; Bankiewicz, Krystof; Davidow, Amy L; Lu, Zi-Hua; Forsayeth, John; Ledeen, Robert W

2015-01-01

47

GM2 gangliosidosis in British Jacob sheep.  

PubMed

GM2 gangliosidosis (Tay-Sachs disease) was diagnosed in 6- to 8-month-old pedigree Jacob lambs from two unrelated flocks presenting clinically with progressive neurological dysfunction of 10 day's to 8 week's duration. Clinical signs included hindlimb ataxia and weakness, recumbency and proprioceptive defects. Histopathological examination of the nervous system identified extensive neuronal cytoplasmic accumulation of material that stained with periodic acid--Schiff and Luxol fast blue. Electron microscopy identified membranous cytoplasmic bodies within the nervous system. Serum biochemistry detected a marked decrease in hexosaminidase A activity in the one lamb tested, when compared with the concentration in age matched controls and genetic analysis identified a mutation in the sheep hexa allele G444R consistent with Tay-Sachs disease in Jacob sheep in North America. The identification of Tay-Sachs disease in British Jacob sheep supports previous evidence that the mutation in North American Jacob sheep originated from imported UK stock. PMID:24309906

Wessels, M E; Holmes, J P; Jeffrey, M; Jackson, M; Mackintosh, A; Kolodny, E H; Zeng, B J; Wang, C B; Scholes, S F E

2014-01-01

48

[Synthesis of aminoethylglycosides with oligosaccharide GM1 and asialo-GM1 ganglioside chains].  

PubMed

4'-O-Glycosylation of 2-azidoethyl 2,3,6-tri-O-benzyl-4-O-(2,3-di-O- benzyl-6-O-benzoyl-beta-D-galactopyranosyl)-beta-D-glucopyranoside with a disaccharide donor, 4-trichloroacetamidophenyl 4,6-di-O-acetyl-2-deoxy-3-O-(2,3,4,6-tetra-O-acetyl-beta-D- galactopyranosyl)-1-thio-2-trichloroacetamido-beta-D-galactopyranoside, in dichloromethane in the presence of N-iodosuccinimide and trifluoromethanesulfonic acid resulted in a tetrasaccharide, 2-azidoethyl (2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-(1-->3)- (4,6-di-O-acetyl-2-deoxy-2-trichloroacetamido-beta-D-galactopyranosyl)- (1-->4)-(2,3-di-O-benzyl-6-O-benzoyl-beta-D-galactopyranosyl)- (1-->4)-2,3,6-tri-O-benzyl-beta-D-glucopyranoside, in 69% yield. The complete removal of O-protecting groups in the tetrasaccharide, the replacement of N-trichloroacetyl by N-acetyl group, and the reduction of the aglycone azide group to amine led to the target aminoethyl glycoside of beta-D-Gal- (1-->3)-beta-D-GalNAc-(1-->4)-beta-D-Gal-(1-->4)-beta-D-Glc-OCH2CH2NH2 containing the oligosaccharide chain of asialo-GM1 ganglioside in 72% overall yield. Selective 3'-O-glycosylation of 2-azidoethyl 2,3,6-tri-O- benzyl-4-O-(2,6-di-O-benzyl-beta-D-galactopyranosyl)-beta-D-glucopyranoside with thioglycoside methyl (ethyl 5-acetamido-4,7,8,9-tetra-O- acetyl-3,5-dideoxy-2-thio-D-glycero-alpha-D-galacto-2-nonulopyranosyl)oate in acetonitrile in the presence of N-iodosuccinimide and trifluoroacetic acid afforded 2-azidoethyl [methyl (5-acetamido-4,7,8,9-tetra-O-acetyl- 3,5-dideoxy-D-glycero-alpha-D-galacto-2-nonulopyranosyl)oate in acetonitrile in the presence of N-iodosuccinimide and tri-fluoracetic acid afforded 2-azidoethyl[methyl (5-acetamido-4,7,8,9-tetra-O-acetyl- 3,5-dideoxy-D-glycero-alpha-D-galacto-2-nonulopyranosyl) (2,6-di-O-benzyl-beta-D-galactopyranosyl)-(1-->4)-2,3,6-tri-O-benzyl-beta-D- glucopyranoside, the selectively protected derivative of the oligosaccharide chain of GM3 ganglioside, in 79% yield. Its 4'-O-glycosylation with a disaccharide glycosyl donor, (4-trichloroacetophenyl-4,6-di-O-acetyl-2-deoxy-3-O-(2,3,4,6-tetra-O- acetyl-beta-D-galactopyranosyl) 1-thio-2-trichloroacetamido-beta-D-galactopyranoside in dichloromethane in the presence of N-iodosuccinimide and trifluoroacetic acid gave 2-azidoethyl (2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)- (1-->3)-(4,6-di-O-acetyl-2-deoxy-2-trichloroacetamido-beta-D- galactopyranosyl)-(1-->4)-[[methyl (5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha-D- galacto-2-nonulopyranosyl)onate]-(2-->3)]-(2,6-di-O-benzyl-beta-D- galactopyranosyl)-(1-->4)-2,3,6-tri-O-benzyl-beta-D-glucopyranoside in 85% yield. The resulting pentasaccharide was O-deprotected, its N-trichloroacetyl group was replaced by N-acetyl group, and the aglycone azide group was reduced to afford in 85% overall yield aminoethyl glycoside of beta-D-Gal-(1-->3)-beta-D-GalNAc-(1-->4)-[alpha-D-Neu5Ac-(2-->3)]- beta-D-Gal-(1-->4)-beta-D-Glc-OCH2CH2NH2 containing the oligosaccharide chain of GM1 ganglioside. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 1; see also http://www.maik.ru. PMID:15040306

Cheshev, P E; Khatuntseva, E A; Tsvetkov, Iu E; Shashkov, A S; Nifant'ev, N E

2004-01-01

49

Galleria mellonella native and analogue peptides Gm1 and ?Gm1. II) anti-bacterial and anti-endotoxic effects.  

PubMed

Antimicrobial peptides (AMPs) are important components of the innate immune system of animals, plants, fungi and bacteria and are recently under discussion as promising alternatives to conventional antibiotics. We have investigated two cecropin-like synthetic peptides, Gm1, which corresponds to the natural overall uncharged Galleria mellonella native peptide and ?Gm1, a modified overall positively charged Gm1 variant. We have analysed these peptides for their potential to inhibit the endotoxin-induced secretion of tumour necrosis factor-? (TNF-?) from human mononuclear cells. Furthermore, in a conventional microbiological assay, the ability of these peptides to inhibit the growth of the rough mutant bacteria Salmonella enterica Minnesota R60 and the polymyxin B-resistant Proteus mirabilis R45 was investigated and atomic force microscopy (AFM) measurements were performed to characterize the morphology of the bacteria treated by the two peptides. We have also studied their cytotoxic properties in a haemolysis assay to clarify potential toxic effects. Our data revealed for both peptides minor anti-inflammatory (anti-endotoxin) activity, but demonstrated antimicrobial activity with differences depending on the endotoxin composition of the respective bacteria. In accordance with the antimicrobial assay, AFM data revealed a stronger morphology change of the R45 bacteria than for the R60. Furthermore, Gm1 had a stronger effect on the bacteria than ?Gm1, leading to a different morphology regarding indentations and coalescing of bacterial structures. The findings verify the biophysical measurements with the peptides on model systems. Both peptides lack any haemolytic activity up to an amount of 100?g/ml, making them suitable as new anti-infective agents. PMID:25016054

Correa, Wilmar; Manrique-Moreno, Marcela; Behrends, Jochen; Patiño, Edwin; Marella, Chakravarthy; Peláez-Jaramillo, Carlos; Garidel, Patrick; Gutsmann, Thomas; Brandenburg, Klaus; Heinbockel, Lena

2014-10-01

50

Pyrimethamine as a potential pharmacological chaperone for late-onset forms of GM2 gangliosidosis.  

PubMed

Late-onset GM2 gangliosidosis is composed of two related, autosomal recessive, neurodegenerative diseases, both resulting from deficiency of lysosomal, heterodimeric beta-hexosaminidase A (Hex A, alphabeta). Pharmacological chaperones (PC) are small molecules that can stabilize the conformation of a mutant protein, allowing it to pass the quality control system of the endoplasmic reticulum. To date all successful PCs have also been competitive inhibitors. Screening for Hex A inhibitors in a library of 1040 Food Drug Administration-approved compounds identified pyrimethamine (PYR (2,4-diamino 5-(4-chlorophenyl)-6-ethylpyrimidine)) as the most potent inhibitor. Cell lines from 10 late-onset Tay-Sachs (11 alpha-mutations, 2 novel) and 7 Sandhoff (9 beta-mutations, 4 novel) disease patients, were cultured with PYR at concentrations corresponding to therapeutic doses. Cells carrying the most common late-onset mutation, alphaG269S, showed significant increases in residual Hex A activity, as did all 7 of the beta-mutants tested. Cells responding to PC treatment included those carrying mutants resulting in reduced Hex heat stability and partial splice junction mutations of the inherently less stable alpha-subunit. PYR, which binds to the active site in domain II, was able to function as PC even to domain I beta-mutants. We concluded that PYR functions as a mutation-specific PC, variably enhancing residual lysosomal Hex A levels in late-onset GM2 gangliosidosis patient cells. PMID:17237499

Maegawa, Gustavo H B; Tropak, Michael; Buttner, Justin; Stockley, Tracy; Kok, Fernando; Clarke, Joe T R; Mahuran, Don J

2007-03-23

51

GM2-Gangliosidosis (Sandhoff and Tay Sachs disease): Diagnosis and Neuroimaging Findings (An Iranian Pediatric Case Series)  

PubMed Central

Objective GM2-Gangliosidosis disease is a rare autosomal recessive genetic disorder that includes two disorders (Tay–Sachs and Sandhoff disease).These disorders cause a progressive deterioration of nerve cells and inherited deficiency in creating hexosaminidases A, B, and AB. Materials & Methods Patients who were diagnosed withGM2-Gangliosidosis in the Neurology Department of Mofid Children’s Hospital in Tehran, Iran from October 2009 to February 2014were included in our study. The disorder was confirmed by neurometabolic and enzyme level detection of hexosaminidases A, B, and AB in reference to Wagnester Laboratory in Germany. We assessed age, gender, past medical history, developmental status, clinical manifestations, and neuroimaging findings of 9 patients with Sandhoff disease and 9 with Tay Sachs disease. Results 83% of our patients were the offspring of consanguineous marriages. All of them had a developmental disorder as a chief complaint. 38%of patients had a history of developmental delay or regression and 22% had seizures. The patients with Sandhoff and Tay Sachs disease were followed for approximately 5 years and the follow-up showed all patients were bedridden or had expired due to refractory seizures, pneumonia aspiration, or swallowing disorders. Neuro-imaging findings included bilateral thalamic involvement, brain atrophy, and hypo myelination in near half of our patients (48%). Conclusion According to the results of this study, we suggest that cherry-red spots, hyperacusis, refractory seizures, and relative parents in children with developmental delay and/or regression should be considered for assessment of GM2-Gangliosidosis disease. PMID:25143775

KARIMZADEH, Parvaneh; JAFARI, Narjes; NEJAD BIGLARI, Habibeh; JABBEH DARI, Sayena; AHMAD ABADI, Farzad; ALAEE, Mohammad-Reza; NEMATI, Hamid; SAKET, Sasan; TONEKABONI, Seyed Hasan; TAGHDIRI, Mohammad-Mahdi; GHOFRANI, Mohammad

2014-01-01

52

THE INVESTIGATION ON THE RATIONALE OF GM (1,1) MODEL  

Microsoft Academic Search

Abstract: The powerful GM(1,1) model in grey theory has been reported successful applications in industries, agriculture, banking and medical research. Nevertheless the underlying mechanism of GM(1,1) modeling is still unclear. In this paper, based on the fundamental fact that parameter estimation problem is just a mathematical optimization, we explore the rationale of GM(1,1) modeling in terms of least-square estimation subject

R. Guo; T. Dunne; Y. H. Cui

53

On multivalent receptor activity of GM1 in cholesterol containing membranes.  

PubMed

Gangliosides located at the outer leaflet of plasma membrane are molecules that either participate in recognizing of exogenous ligand molecules or exhibit their own receptor activity, which are both essential phenomena for cell communication and signaling as well as for virus and toxin entry. Regulatory mechanisms of lipid-mediated recognition are primarily subjected to the physical status of the membrane in close vicinity of the receptor. Concerning the multivalent receptor activity of the ganglioside GM1, several regulatory strategies dealing with GM1 clustering and cholesterol involvement have been proposed. So far however, merely the isolated issues were addressed and no interplay between them investigated. In this work, several advanced fluorescence techniques such as Z-scan fluorescence correlation spectroscopy, Förster resonance energy transfer combined with Monte Carlo simulations, and a newly developed fluorescence antibunching assay were employed to give a more complex portrait of clustering and cholesterol involvement in multivalent ligand recognition of GM1. Our results indicate that membrane properties have an impact on a fraction of GM1 molecules that is not available for the ligand binding. While at low GM1 densities (~1 %) it is the cholesterol that turns GM1 headgroups invisible, at higher GM1 level (~4 %) it is purely the local density of GM1 molecules that inhibits the recognition. At medium GM1 content, cooperation of the two phenomena occurs. This article is part of a Special Issue entitled: Nanoscale membrane organisation and signalling. PMID:25101973

Šachl, Radek; Amaro, Mariana; Aydogan, Gokcan; Koukalová, Alena; Mikhalyov, Ilya I; Boldyrev, Ivan A; Humpolí?ková, Jana; Hof, Martin

2015-04-01

54

Thermodynamic characterisation of the mutated isoenzyme A of ?- N-acetylhexosaminidase in GM2-gangliosidosis B1 variant  

Microsoft Academic Search

Here we report the determination of the activation energies of the plasma isoenzymes of ?-N-acetylhexosaminidase (Hex, EC 3.2.1.52), isolated by chromatography in DEAE-cellulose, using the neutral chromogenic substrate 3,3?dichlorophenylsulfonphthaleinyl-N-acetyl-?-d-glucosaminide. The activation energy of mutated Hex A isoenzyme (Ea?71.5 kJ\\/mol) from a patient with GM2-gangliosidosis B1 variant, homozygote for the G533?A (Argl78His) mutation, was significantly higher than that of normal Hex

Luis F. Pérez; Helena M. Ribeiro; J. Antonio Casal; Rui A. Pinto; M. Clara Sá Miranda; J. Carlos Tutor

1999-01-01

55

Neuropathology of chronic GM2 gangliosidosis due to hexosaminidase A deficiency.  

PubMed

Autopsy studies of late-onset GM2 gangliosidosis are sparse and only one adult case is on record. The case of partial Hex A deficiency presented here started in childhood as spinal muscular atrophy which progressed slowly over 4 decades. Cognitive function remained intact throughout the entire course, but during the last few years of life allodynia supervened. The patient died at 44 years of age. In good correlation with clinical observations the autopsy findings showed the most severe accumulation of lipid and consequent regressive change in the anterior horns of the spinal cord. Extensive but less severe storage was found in other spinal cord neurons, brain stem and selected basal ganglia. Cerebral cortex was virtually spared by storage but was the site of excessive formation of lipofuscin which was also present in many other neurons in the CNS. Marked storage and ganglionic loss was also found in the dorsal root ganglia, and the fasciculus gracilis was severely depleted of myelinated fibers. Electron microscopy showed accumulated gangliosides almost exclusively in the form of single and coalescing zebra bodies. In conclusion, the pathology in this case of chronic GM2 gangliosidosis, though in part conforming with previous observations, differed in several aspects. First, the cerebral cortex was--with only a few exceptions--free of ganglioside storage. Also spared was the cerebellum. In addition, homogeneous accumulation of zebra bodies contrasted with heterogeneity of neuronal inclusions found in other chronic cases. Finally, the involvement of sensory neurons was prominent and potentially related to allodynia. Molecular study of HEXA gene in this patient showed an TATC1278/? genotype. PMID:18808061

Kornfeld, M

2008-01-01

56

N-Glycolyl GM1 Ganglioside as a Receptor for Simian Virus 40? †  

PubMed Central

Carbohydrate microarrays have emerged as powerful tools in analyses of microbe-host interactions. Using a microarray with 190 sequence-defined oligosaccharides in the form of natural glycolipids and neoglycolipids representative of diverse mammalian glycans, we examined interactions of simian virus 40 (SV40) with potential carbohydrate receptors. While the results confirmed the high specificity of SV40 for the ganglioside GM1, they also revealed that N-glycolyl GM1 ganglioside [GM1(Gc)], which is characteristic of simian species and many other nonhuman mammals, is a better ligand than the N-acetyl analog [GM1(Ac)] found in mammals, including humans. After supplementing glycolipid-deficient GM95 cells with GM1(Ac) and GM1(Gc) gangliosides and the corresponding neoglycolipids with phosphatidylethanolamine lipid groups, it was found that GM1(Gc) analogs conferred better virus binding and infectivity. Moreover, we visualized the interaction of NeuGc with VP1 protein of SV40 by molecular modeling and identified a conformation for GM1(Gc) ganglioside in complex with the virus VP1 pentamer that is compatible with its presentation as a membrane receptor. Our results open the way not only to detailed studies of SV40 infection in relation to receptor expression in host cells but also to the monitoring of changes that may occur with time in receptor usage by the virus. PMID:17855525

Campanero-Rhodes, Maria A.; Smith, Alicia; Chai, Wengang; Sonnino, Sandro; Mauri, Laura; Childs, Robert A.; Zhang, Yibing; Ewers, Helge; Helenius, Ari; Imberty, Anne; Feizi, Ten

2007-01-01

57

Condensing and Fluidizing Effects of Ganglioside GM1 on Phospholipid Films  

E-print Network

regulation (4). Although a minor component in most cells, they constitute 5­10% of the total lipid massCondensing and Fluidizing Effects of Ganglioside GM1 on Phospholipid Films Shelli L. Frey,* Eva Y of the ganglioside molecules in a mixed membrane. The effects induced by GM1 on the mean molecular area of the binary

Lee, Ka Yee C.

58

Influence of GM1 gangliosides on the growth of cultured rat embryonic serotonergic neurons.  

PubMed

GM1 gangliosides were added to the medium of cultured raphe neurons enriched in the serotonergic phenotype in order to study their influence on biochemical and morphological growth parameters of serotonergic neurons. After 2 days of culture in the presence of GM1, specific uptake of serotonin measured by scintillation counting exhibited a moderate but significant increase for a GM1 concentration of 5 X 10(-8) M. Morphological parameters of 5-HT neurons were measured after immunocytochemical staining with specific serotonin antiserum, and digitalization of immunoreactive cells. Eight parameters were studied; for concentrations of 5 X 10(-8) and 10(-7) M of GM1, the absolute neuritic field area and the total length of the segments were significantly increased, whereas the number of neuritic segments, and their mean length were not modified. We conclude that GM1 ganglioside has a significant influence on the growth of serotonergic neurons. Moreover, electron microscopy showed, on treated cultures, a dramatic increase of the number of spicules all along the neuron's process, suggesting that GM1 could act by modifying the attachment of cells to their substrate. The possible molecular mechanisms of the action of GM1 are discussed. PMID:2603760

Marlier, L; Poulat, P; König, N; Drian, M J; Privat, A

1989-01-01

59

Effects of Methylprednisolone And Ganglioside GM-1 on a Spinal Lesion: A Functional Analysis  

PubMed Central

OBJECTIVES The pharmacological effects of methylprednisolone (MP) and ganglioside GM-1 on spinal injuries have been thoroughly investigated, but only a few studies have evaluated the interaction between these two drugs. METHODS Twenty-four Wistar rats were subjected to contusive injury of the spinal cord produced by the NYU system. These animals were divided into four groups: group I was injected with MP; group II was injected with GM-1; group III was injected with MP together with GM-1; and group control received physiological serum. The animals were evaluated with regard to their recovery of locomotive function by means of the BBB test on the second, seventh and fourteenth days after receiving the contusive injury to the spinal cord. They were sacrificed on the fourteenth day. RESULTS This study demonstrated that the MP and GM-1 groups presented functional results that were better than those of the control group, although the enhanced recovery of group II (GM-1) relative to the control group was not statistically significant (p>0.05). The most notable recovery of locomotive function was observed in the group that received MP alone (p<0.05). The group that received MP together with GM-1 presented results that were better than those of the control group (p<0.05). CONCLUSION Administration of methylprednisolone alone or with GM-1 was shown to be effective for recovery of locomotive function. Combined administration of these drugs resulted in better outcomes than administration of methylprednisolone alone. PMID:18568249

Carvalho, Márcio Oliveira Penna; de Barros Filho, Tarcisio Eloy Pessoa; Tebet, Marcos Antonio

2008-01-01

60

Pathology of GM2 gangliosidosis in Jacob sheep.  

PubMed

The G(M2) gangliosidoses are a group of lysosomal storage diseases caused by defects in the genes coding for the enzyme hexosaminidase or the G(M2) activator protein. Four Jacob sheep from the same farm were examined over a 3-year period for a progressive neurologic disease. Two lambs were 6-month-old intact males and 2 were 8-month-old females. Clinical findings included ataxia in all 4 limbs, proprioceptive deficits, and cortical blindness. At necropsy, the nervous system appeared grossly normal. Histologically, most neurons within the brain, spinal cord, and peripheral ganglia were enlarged, and the cytoplasm was distended by foamy to granular material that stained positively with Luxol fast blue and Sudan black B stains. Other neuropathologic findings included widespread astrocytosis, microgliosis, and scattered spheroids. Electron microscopy revealed membranous cytoplasmic bodies within the cytoplasm of neurons. Biochemical and molecular genetic studies confirmed the diagnosis of G(M2) gangliosidosis. This form of G(M2) gangliosidosis in Jacob sheep is very similar to human Tay-Sachs disease and is potentially a useful animal model. PMID:21123862

Porter, B F; Lewis, B C; Edwards, J F; Alroy, J; Zeng, B J; Torres, P A; Bretzlaff, K N; Kolodny, E H

2011-07-01

61

Recovery from Experimental Parkinsonism in Primates with GM1 Ganglioside Treatment  

NASA Astrophysics Data System (ADS)

A parkinsonian syndrome can be produced in nonhuman primates by administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Parkinsonian-like symptoms induced acutely by MPTP were ameliorated after treatment with GM1 ganglioside, a substance shown to have neurotrophic effects on the damaged dopamine system in rodents. Treatment with GM1 ganglioside also increased striatal dopamine and metabolite levels and enhanced the dopaminergic innervation of the striatum as demonstrated by tyrosine hydroxylase immunohistochemistry. These results suggest that GM1 ganglioside may hold promise as a therapeutic agent for the treatment of Parkinson's disease.

Schneider, J. S.; Pope, Anne; Simpson, Kimberly; Taggart, James; Smith, M. G.; Distefano, L.

1992-05-01

62

MECHANISMS UNDERLYING THE MICRON-SCALE SEGREGATION OF STEROLS AND GM1 IN LIVE MAMMALIAN SPERM  

PubMed Central

We demonstrate for the first time that a stable, micron-scale segregation of focal enrichments of sterols exists at physiological temperature in the plasma membrane of live murine and human sperm. These enrichments of sterols represent microheterogeneities within this membrane domain overlying the acrosome. Previously, we showed that cholera toxin subunit B (CTB), which binds the glycosphingolipid, GM1, localizes to this same domain in live sperm. Interestingly, the GM1 undergoes an unexplained redistribution upon cell death. We now demonstrate that GM1 is also enriched in the acrosome, an exocytotic vesicle. Transfer of lipids between this and the plasma membrane occurs at cell death, increasing GM1 in the plasma membrane without apparent release of acrosomal contents. This finding provides corroborative support for an emerging model of regulated exocytosis in which membrane communications might occur without triggering the “acrosome reaction.” Comparison of the dynamics of CTB-bound endogenous GM1 and exogenous BODIPY-GM1 in live murine sperm demonstrate that the sub-acrosomal ring functions as a specialized diffusion barrier segregating specific lipids within the sperm head plasma membrane. Our data show significant differences between endogenous lipids and exogenous lipid probes in terms of lateral diffusion. Based on these studies, we propose a hierarchical model to explain the segregation of this sterol- and GM1-enriched domain in live sperm, which is positioned to regulate sperm fertilization competence and mediate interactions with the oocyte. Moreover, our data suggest potential origins of sub-types of membrane raft microdomains enriched in sterols and/or GM1 that can be separated biochemically. PMID:19012288

Selvaraj, Vimal; Asano, Atsushi; Buttke, Danielle E.; Sengupta, Prabuddha; Weiss, Robert S.; Travis, Alexander J.

2009-01-01

63

Capability of ganglioside GM1 in modulating interactions, structure, location and dynamics of peptides/proteins: biophysical approaches: interaction of ganglioside GM1 with peptides/proteins.  

PubMed

Gangliosides, are glycosphingolipids, present in all vertebrate plasma membranes with particular abundance in nerve cell membrane. Gangliosides can act as portals for antimicrobial peptides, hormones, viruses, lectins, toxins and pathogens. They are strategically positioned on the outer membrane and hence can participate in a large number of recognition processes. Their abundance in nerve cell membrane makes them "likely" receptor candidates for neuropeptides. In this review we outline our work in the area of GM1-peptide/protein interaction. We have explored the effect of GM1 containing micelles/bicelles on structures of peptides, proteins as well as on denatured proteins. It has been observed that the peptides that are disordered or having random coil structure in aqueous solution, attained an ordered three-dimensional structure when interact with GM1. It is also observed that denatured proteins undergo refolding in presence of ganglioside. Peptides/proteins show stronger interaction with membrane lipid bilayer in presence of ganglioside than that without ganglioside. This review mainly focuses on capability of ganglioside GM1 in modulating interaction, structural, location and dynamics of peptides/proteins using a number of biophysical techniques-solution NMR, DOSY, CD, fluorescence etc. PMID:25178424

Khatun, Ummul Liha; Gayen, Anindita; Mukhopadhyay, Chaitali

2014-10-01

64

Synthesis of novel NBD-GM1 and NBD-GM2 for the transfer activity of GM2-activator protein by a FRET-based assay system.  

PubMed

The ganglioside-activator protein is an essential cofactor for the lysosomal degradation of ganglioside GM2 (GM2) by beta-hexosaminidase A. It mediates the interaction between the water-soluble exohydrolase and its membrane-embedded glycolipid substrate at the lipid-water interphase. Mutations in the gene encoding this glycoprotein result in a fatal neurological storage disorder, the AB variant of GM2-gangliosidosis. In order to efficiently and sensitively probe the glycolipid binding and membrane activity of this cofactor, we synthesized two new fluorescent glycosphingolipid (GSL) probes, 2-NBD-GM1 and 2-NBD-GM2. Both compounds were synthesized in a convergent and multistep synthesis starting from the respective gangliosides isolated from natural sources. The added functionality of 2-aminogangliosides allowed us to introduce the chromophore into the region between the polar head group and the hydrophobic anchor of the lipid. Both fluorescent glycolipids exhibited an extremely low off-rate in model membranes and displayed very efficient resonance energy transfer to rhodamine-dioleoyl phosphoglycerol ethanolamine (rhodamine-PE) as acceptor. The binding to GM2-activator protein (GM2AP) and the degrading enzyme was shown to be unaltered compared to their natural analogues. A novel fluorescence-resonance energy transfer (FRET) assay was developed to monitor in real time the protein-mediated intervesicular transfer of these lipids from donor to acceptor liposomes. The data obtained indicate that this rapid and robust system presented here should serve as a valuable tool to probe quantitatively and comprehensively the membrane activity of GM2AP and other sphingolipid activator proteins and facilitate further structure-function studies aimed at delineating independently the lipid- and the enzyme-binding mode of these essential cofactors. PMID:16079415

Schwarzmann, Günter; Wendeler, Michaela; Sandhoff, Konrad

2005-12-01

65

Interaction of bee venom toxin melittin with ganglioside GM1 bicelle.  

PubMed

Melittin is a bee venom toxin that can act as antimicrobial peptide. Gangliosides are glycosphingolipids that help maintain membrane structure and organization as well as act as anchors for lectins, toxins, pathogens and antimicrobial peptides. Here we investigate interaction of melittin with fast tumbling isotropic control DMPC/CHAPS bicelles and ganglioside doped DMPC/CHAPS/GM1 bicelles. DOSY result shows that larger percentage of peptide binds to GM1 containing bicelles than that of the control PC bicelles. Bound peptide induces leakage of the bicelles entrapped carboxyfluorescein. Percentage of leakage is higher from control PC bicelles than that of the GM1 containing bicelles. In the presence of control PC bicelles melittin acquired fully ?-helical structure. But in the presence of GM1 containing bicelles the peptide is not fully ?-helical i.e., some random coil structure is present in this folded form. The present study shows that GM1 has an effect on membrane active antimicrobial peptide melittin. PMID:23850803

Khatun, Ummul Liha; Mukhopadhyay, Chaitali

2013-01-01

66

Bis(monoacylglycero)phosphate and ganglioside GM1 spontaneously form small homogeneous vesicles at specific concentrations  

SciTech Connect

The morphology and size of hydrated lipid dispersions of bis(monoacylglycero)phosphate (BMP) mixed with varying mole percentages of the ganglioside GM1 were investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Electron paramagnetic resonance (EPR) spectroscopy of these same mixtures, doped at 0.5 mol% with doxyl labeled lipids, was used to investigate acyl-chain packing. Results show that for 20-30% GM1, hydrated BMP:GM1 mixtures spontaneously form small spherical vesicles with diameters {approx}100 nm and a narrow size distribution profile. For other concentrations of GM1, hydrated dispersions with BMP have non-spherical shapes and heterogeneous size profiles, with average vesicle diameters >400 nm. All samples were prepared at pH 5.5 to mimic the lumen acidity of the late endosome where BMP is an essential component of intraendosomal vesicle budding, lipid sorting and trafficking. These findings indicate that GM1 and BMP under a limited concentration range spontaneously form small vesicles of homogeneous size in an energy independent manner without the need of protein templating. Because BMP is essential for intraendosomal vesicle formation, these results imply that lipid-lipid interactions may play a critical role in the endosomal process of lipid sorting and trafficking.

Chebukati, Janetricks N.; Goff, Philip C.; Frederick, Thomas E. [Department of Chemistry, P.O. Box 117200, University of Florida, Gainesville, FL 32611-7200 (United States)] [Department of Chemistry, P.O. Box 117200, University of Florida, Gainesville, FL 32611-7200 (United States); Fanucci, Gail E., E-mail: fanucci@chem.ufl.edu [Department of Chemistry, P.O. Box 117200, University of Florida, Gainesville, FL 32611-7200 (United States)

2010-04-09

67

Bis(monoacylglycero)phosphate and Ganglioside GM1 Spontaneously Form Small Homogeneous Vesicles at Specific Concentrations  

PubMed Central

The morphology and size of hydrated lipid dispersions of bis(monoacylglycero)phosphate (BMP) mixed with varying mole percentages of the ganglioside GM1 were investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Electron paramagnetic resonance (EPR) spectroscopy of these same mixtures, doped at 0.5 mole percent with doxyl labeled lipids, was used to investigate acyl chain packing. Results show that for 20–30% GM1, hydrated BMP:GM1 mixtures spontaneously form small spherical vesicles with diameters ~ 100 nm and a narrow size distribution profile. For other concentrations of GM1, hydrated dispersions with BMP have nonspherical shapes and heterogeneous size profiles, with average vesicle diameters > 400 nm. All samples were prepared at pH 5.5 to mimic the lumen acidity of the late endosome where BMP is an essential component of intraendosomal vesicle budding, lipid sorting and trafficking. These findings indicate that GM1 and BMP under a limited concentration range spontaneously form small vesicles of homogeneous size in an energy independent manner without the need of protein templating. Because BMP is essential for intraendosomal vesicle formation, these results imply that lipid-lipid interactions may play a critical role in the endosomal process of lipid sorting and trafficking. PMID:20206128

Chebukati, Janetricks N.; Goff, Philip C.; Frederick, Thomas E.; Fanucci, Gail E.

2010-01-01

68

Biochemical and molecular aspects of late-onset GM2-gangliosidosis: B1 variant as a prototype.  

PubMed

Clinical phenotypes of GM2-gangliosidosis are complex. In the past 5 years it has become possible to dissect out the phenotypic complexity on the basis of abnormalities on the DNA level. Available data on the 18 disease-causing mutations so far identified in the beta-hexosaminidase alpha-gene allow an oversimplified generalization; mutations that produce no or highly unstable mRNA cause the most severe infantile forms of the disease, while all late-onset forms are due to point mutations within the protein-coding region, which generate stable mRNA and stable mutant protein. The mutation underlying the distinct phenotype of Jewish adult Tay-Sachs disease will be discussed separately by Navon. The prototype of juvenile Tay-Sachs disease is the B1 variant. The disease was first recognized by an apparent discrepancy in the beta-hexosaminidase activities toward the conventional artificial substrates and the natural lipid substrate, GM2-ganglioside. When assayed with the conventional artificial substrates, patients appear reasonably normal while they are severely deficient in hydrolysis of the natural substrate (and more recently the 'sulfated' artificial substrate). The majority of B1 patients fall in the clinical category of juvenile GM2-gangliosidosis. Some of the earlier juvenile patients reported to have partial hexosaminidase A deficiency are likely to be B1 variant. Two point mutations, occurring at a mutation hot spot, CpG, and both affecting the same codon, have been described as the causes of the B1 variant phenotype; G533----A, Arg178----His; and C532----T, Arg178----Cys. The latter mutation has been found so far only in one Czechoslovakian family. In contrast, the former mutation has a wide geographic and ethnic distribution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1840099

Suzuki, K; Vanier, M T

1991-01-01

69

Mechanism of amyloid ?-protein aggregation mediated by GM1 ganglioside clusters.  

PubMed

It is widely accepted that the conversion of the soluble, nontoxic amyloid ?-protein (A?) monomer to aggregated toxic A? rich in ?-sheet structures is central to the development of Alzheimer's disease. However, the mechanism of the abnormal aggregation of A? in vivo is not well understood. We have proposed that ganglioside clusters in lipid rafts mediate the formation of amyloid fibrils by A?, the toxicity and physicochemical properties of which are different from those of amyloids formed in solution. In this paper, the mechanism by which A?-(1-40) fibrillizes in raftlike lipid bilayers composed of monosialoganglioside GM1, cholesterol, and sphingomyelin was investigated in detail on the basis of singular-value decomposition of circular dichroism data and analysis of fibrillization kinetics. At lower protein densities in the membrane (A?:GM1 ratio of less than ?0.013), only the helical species exists. At intermediate protein densities (A?:GM1 ratio between ?0.013 and ?0.044), the helical species and aggregated ?-sheets (?15-mer) coexist. However, the ?-structure is stable and does not form larger aggregates. At A?:GM1 ratios above ?0.044, the ?-structure is converted to a second, seed-prone ?-structure. The seed recruits monomers from the aqueous phase to form amyloid fibrils. These results will shed light on a molecular mechanism for the pathogenesis of the disease. PMID:21682276

Ikeda, Keisuke; Yamaguchi, Takahiro; Fukunaga, Saori; Hoshino, Masaru; Matsuzaki, Katsumi

2011-07-26

70

Colocalization of the Ganglioside GM1 and Cholesterol Detected by Secondary Ion Mass Spectrometry  

E-print Network

Colocalization of the Ganglioside GM1 and Cholesterol Detected by Secondary Ion Mass Spectrometry here the use of secondary ion mass spectrometry (SIMS) to image the cholesterol-dependent cohesive spectrometry, directly measuring the mass of components or isotopically labeled fragments from the co

Boxer, Steven G.

71

GM1 structure determines SV40-induced membrane invagination and infection.  

PubMed

Incoming simian virus 40 (SV40) particles enter tight-fitting plasma membrane invaginations after binding to the carbohydrate moiety of GM1 gangliosides in the host cell plasma membrane through pentameric VP1 capsid proteins. This is followed by activation of cellular signalling pathways, endocytic internalization and transport of the virus via the endoplasmic reticulum to the nucleus. Here we show that the association of SV40 (as well as isolated pentameric VP1) with GM1 is itself sufficient to induce dramatic membrane curvature that leads to the formation of deep invaginations and tubules not only in the plasma membrane of cells, but also in giant unilamellar vesicles (GUVs). Unlike native GM1 molecules with long acyl chains, GM1 molecular species with short hydrocarbon chains failed to support such invagination, and endocytosis and infection did not occur. To conceptualize the experimental data, a physical model was derived based on energetic considerations. Taken together, our analysis indicates that SV40, other polyoma viruses and some bacterial toxins (Shiga and cholera) use glycosphingolipids and a common pentameric protein scaffold to induce plasma membrane curvature, thus directly promoting their endocytic uptake into cells. PMID:20023649

Ewers, Helge; Römer, Winfried; Smith, Alicia E; Bacia, Kirsten; Dmitrieff, Serge; Chai, Wengang; Mancini, Roberta; Kartenbeck, Jürgen; Chambon, Valérie; Berland, Ludwig; Oppenheim, Ariella; Schwarzmann, Günter; Feizi, Ten; Schwille, Petra; Sens, Pierre; Helenius, Ari; Johannes, Ludger

2010-01-01

72

Co-localization of the Ganglioside GM1 and Cholesterol Detected by Secondary Ion Mass Spectrometry  

PubMed Central

The characterization of the lateral organization of components in biological membranes and the evolution of this arrangement in response to external triggers remains a major challenge. The concept of lipid rafts is widely invoked, however, direct evidence of the existence of these ephemeral entities remains elusive. We report here the use of Secondary Ion Mass Spectrometry (SIMS) to image the cholesterol-dependent cohesive phase separation of the ganglioside GM1 into nano and micro-scale assemblies in a canonical lipid raft composition of lipids. This assembly of domains was interrogated in a model membrane system composed of palmitoyl sphingomyelin (PSM), cholesterol, and an unsaturated lipid (dioleoylphosphatidylcholine, DOPC). Orthogonal isotopic labeling of every lipid bilayer component and monofluorination of GM1 allowed generation of molecule specific images using a NanoSIMS. Simultaneous detection of six different ion species in SIMS, including secondary electrons, was used to generate ion ratio images whose signal intensity values could be correlated to composition through the use of calibration curves from standard samples. Images of this system provide the first direct, molecule specific, visual evidence for the co-localization of cholesterol and GM1 in supported lipid bilayers and further indicate the presence of three compositionally distinct phases: (1) the interdomain region; (2) micrometer-scale domains (d>3 ?m); and, (3) nanometer-scale domains (d=100 nm ? 1 ?m) localized within the micrometer-scale domains and the interdomain region. PSM-rich, nanometer-scale domains prefer to partition within the more ordered, cholesterol-rich/DOPC-poor/GM1-rich micrometer-scale phase, while GM1-rich, nanometer-scale domains prefer to partition within the surrounding, disordered, cholesterol-poor/PSM-rich/DOPC-rich interdomain phase. PMID:23514537

Lozano, Mónica M.; Liu, Zhao; Sunnick, Eva; Janshoff, Andreas; Kumar, Krishna; Boxer, Steven G.

2013-01-01

73

Neurotrophic Effects of GM1 Ganglioside and Electrical Stimulation on Cochlear Spiral Ganglion Neurons in Cats Deafened as Neonates  

PubMed Central

Previous studies have shown that electrical stimulation of the cochlea by a cochlear implant promotes increased survival of spiral ganglion (SG) neurons in animals deafened early in life (Leake et al., 1999). However, electrical stimulation only partially prevents SG degeneration after deafening, and other neurotrophic agents that may be used along with an implant are of great interest. GM1 ganglioside is a glycosphingolipid that has been reported to be beneficial in treating stroke, spinal cord injuries and Alzheimer disease. GM1 activates trKB signaling and potentiates neurotrophins, and exogenous administration of GM1 has been shown to reduce SG degeneration after hearing loss. In the present study, animals were deafenedas neonates and received daily injections of GM1 (beginning either at birth or after animals were deafened and continuing until the time of cochlear implantation). GM1-treated and deafened control groups were examined at 7–8 weeks of age; additional GM1 and non-GM1 deafened control groups received a cochlear implant at 7–8 weeks of age and at least 6 months of unilateral electrical stimulation. Electrical stimulation elicited a significant trophic effect in both the GM1 group and the non-GM1 group as compared to the contralateral, non-stimulated ears. The results also demonstrated a modest initial improvement in SG density with GM1 treatment, which was maintained by and additive with the trophic effect of subsequent electrical stimulation. However, in the deafened ears contralateral to the implant, SG soma size was severely reduced several months after withdrawal of GM1 in the absence of electrical activation. PMID:17311311

Leake, Patricia A.; Hradek, Gary T.; Vollmer, Maike; Rebscher, Stephen J.

2008-01-01

74

Using a set of GM(1,1) models to predict values of diagnostic symptoms  

NASA Astrophysics Data System (ADS)

The main purpose of this study is to develop a methodology of predicting values of vibration symptoms of fan mills in a combined heat and power (CHP) plant. The study was based on grey system theory and GM(1,1) prognostic models with different window sizes for estimating model parameters. Such models have a number of features that are desirable from the point of view of data characteristics collected by the diagnostic system. When using moving window, GM(1,1) models tend to be adaptive. However, selecting an inappropriate window size can result in excessive forecast errors. The present study proposes three possible methods that can be used in automated diagnostic systems to counteract the excessive increase in the forecast error. A comparative analysis of their performance was conducted using data from fan mills in order to select the method which minimises the forecast error.

Tabaszewski, Maciej; Cempel, Czeslaw

2015-02-01

75

Gangliosides GM1 and GM3 in the Living Cell Membrane Form Clusters Susceptible to Cholesterol Depletion and Chilling  

PubMed Central

Presence of microdomains has been postulated in the cell membrane, but two-dimensional distribution of lipid molecules has been difficult to determine in the submicrometer scale. In the present paper, we examined the distribution of gangliosides GM1 and GM3, putative raft molecules in the cell membrane, by immunoelectron microscopy using quick-frozen and freeze-fractured specimens. This method physically immobilized molecules in situ and thus minimized the possibility of artifactual perturbation. By point pattern analysis of immunogold labeling, GM1 was shown to make clusters of <100 nm in diameter in normal mouse fibroblasts. GM1-null fibroblasts were not labeled, but developed a similar clustered pattern when GM1 was administered. On cholesterol depletion or chilling, the clustering of both endogenous and exogenously-loaded GM1 decreased significantly, but the distribution showed marked regional heterogeneity in the cells. GM3 also showed cholesterol-dependent clustering, and although clusters of GM1 and GM3 were found to occasionally coincide, these aggregates were separated in most cases, suggesting the presence of heterogeneous microdomains. The present method enabled to capture the molecular distribution of lipids in the cell membrane, and demonstrated that GM1 and GM3 form clusters that are susceptible to cholesterol depletion and chilling. PMID:17392511

Fujita, Akikazu; Cheng, Jinglei; Hirakawa, Minako; Furukawa, Koichi; Kusunoki, Susumu

2007-01-01

76

Lipid-sorting by ceramide structure from plasma membrane to ER for the cholera toxin receptor ganglioside GM1  

PubMed Central

SUMMARY The glycosphingolipid GM1 binds cholera toxin (CT) on host cells and carries it retrograde from the plasma membrane (PM) through endosomes, the trans-Golgi (TGN), and the endoplasmic reticulum (ER) to induce toxicity. To elucidate how a membrane lipid can specify trafficking in these pathways, we synthesized GM1 isoforms with alternate ceramide domains and imaged their trafficking in live cells. Only GM1 with unsaturated acyl chains sorted efficiently from PM to TGN and ER. Toxin binding, which effectively crosslinks GM1 lipids, was dispensable, but membrane cholesterol and the lipid raft-associated proteins actin and flotillin were required. The results implicate a protein-dependent mechanism of lipid-sorting by ceramide structure and provide a molecular explanation for the diversity and specificity of retrograde trafficking by CT in host cells. PMID:22975326

Chinnapen, Daniel J.-F.; Hsieh, Wan-Ting; te Welscher, Yvonne M.; Saslowsky, David E.; Kaoutzani, Lydia; Brandsma, Eelke; D’Auria, Ludovic; Park, Hyejung; Wagner, Jessica S.; Drake, Kimberly R.; Kang, Minchul; Benjamin, Thomas; Ullman, M. David; Costello, Catherine E.; Kenworthy, Anne K.; Baumgart, Tobias; Massol, Ramiro H.; Lencer, Wayne I.

2012-01-01

77

GM1 ganglioside attenuates convulsions and thiobarbituric acid reactive substances production induced by the intrastriatal injection of methylmalonic acid  

Microsoft Academic Search

The effects of the administration of monosialoganglioside (GM1) on methylmalonic acid (MMA)-induced convulsions, production of thiobarbituric acid reactive substances (TBARS) and on the striatal content of ascorbic acid and total non-protein thiol (SH) groups were evaluated in adult male rats. Animals received two intraperitoneal injections of GM1 (50mg\\/kg) or saline (0.85% NaCl) spaced 24h apart. Thirty minutes after the second

Michele Rechia Fighera; Juliana Sartori Bonini; Telma Grendene de Oliveira; Roberto Frussa-Filho; João Batista Teixeira Rocha; Carlos Severo Dutra-Filho; Maribel Antonello Rubin; Carlos Fernando Mello

2003-01-01

78

pH-dependent Formation of Membranous Cytoplasmic Body-Like Structure of Ganglioside GM1/Bis(Monoacylglycero)Phosphate  

E-print Network

pH-dependent Formation of Membranous Cytoplasmic Body-Like Structure of Ganglioside GM1/Bis(Monoacylglycero)Phosphate) phos- phate (BMP, also known as lysobisphosphatidic acid) were examined at various pH conditions by freeze-fracture electron micros- copy and small-angle x-ray scattering. At pH 8.5­6.5, a GM1/BMP (1:1 mol

Paris-Sud XI, Université de

79

Binding, Conformational Transition and Dimerization of Amyloid-? Peptide on GM1-Containing Ternary Membrane: Insights from Molecular Dynamics Simulation  

PubMed Central

Interactions of amyloid-? (A?) with neuronal membrane are associated with the progression of Alzheimer’s disease (AD). Ganglioside GM1 has been shown to promote the structural conversion of A? and increase the rate of peptide aggregation; but the exact nature of interaction driving theses processes remains to be explored. In this work, we have carried out atomistic-scale computer simulations (totaling 2.65 µs) to investigate the behavior of A? monomer and dimers in GM1-containing raft-like membrane. The oligosaccharide head-group of GM1 was observed to act as scaffold for A?-binding through sugar-specific interactions. Starting from the initial helical peptide conformation, a ?-hairpin motif was formed at the C-terminus of the GM1-bound A?-monomer; that didn’t appear in absence of GM1 (both in fluid POPC and liquid-ordered cholesterol/POPC bilayers and also in aqueous medium) within the simulation time span. For A?-dimers, the ?-structure was further enhanced by peptide-peptide interactions, which might influence the propensity of A? to aggregate into higher-ordered structures. The salt-bridges and inter-peptide hydrogen bonds were found to account for dimer stability. We observed spontaneous formation of intra-peptide D23-K28 salt-bridge and a turn at V24GSN27 region - long been accepted as characteristic structural-motifs for amyloid self-assembly. Altogether, our results provide atomistic details of A?-GM1 and A?-A? interactions and demonstrate their importance in the early-stages of GM1-mediated A?-oligomerisation on membrane surface. PMID:23951128

Manna, Moutusi; Mukhopadhyay, Chaitali

2013-01-01

80

In vivo biodistribution of prion- and GM1-targeted polymersomes following intravenous administration in mice.  

PubMed

Due to the aging of the population, the incidence of neurodegenerative diseases, such as Parkinson's and Alzheimer's, is expected to grow and, hence, the demand for adequate treatment modalities. However, the delivery of medicines into the brain for the treatment of brain-related diseases is hampered by the presence of a tight layer of endothelial cells that forms the blood-brain barrier (BBB). Furthermore, most conventional drugs lack stability and/or bioavailability. These obstacles can be overcome by the application of nanocarriers, in which the therapeutic entity has been incorporated, provided that they are effectively targeted to the brain endothelial cell layer. Drug nanocarriers decorated with targeting ligands that bind BBB receptors may accumulate efficiently at/in brain microvascular endothelium and hence represent a promising tool for brain drug delivery. Following the accumulation of drug nanocarriers at the brain vasculature, the drug needs to be transported across the brain endothelial cells into the brain. Transport across brain endothelial cells can occur via passive diffusion, transport proteins, and the vesicular transport pathways of receptor-mediated and adsorptive-mediated transcytosis. When a small lipophilic drug is released from its carrier at the brain vasculature, it may enter the brain via passive diffusion. On the other hand, the passage of intact nanocarriers, which is necessary for the delivery of larger and more hydrophilic drugs into brain, may occur via active transport by means of transcytosis. In previous work we identified GM1 ganglioside and prion protein as potential transcytotic receptors at the BBB. GM1 is a glycosphingolipid that is ubiquitously present on the endothelial surface and capable of acting as the transcytotic receptor for cholera toxin B. Likewise, prion protein has been shown to have transcytotic capacity at brain endothelial cells. Here we determine the transcytotic potential of polymersome nanocarriers functionalized with GM1- and prion-targeting peptides (G23, P50 and P9), that were identified by phage display, in an in vitro BBB model. In addition, the biodistribution of polymersomes functionalized with either the prion-targeting peptide P50 or the GM1-targeting peptide G23 is determined following intravenous injection in mice. We show that the prion-targeting peptides do not induce efficient transcytosis of polymersomes across the BBB in vitro nor induce accumulation of polymersomes in the brain in vivo. In contrast, the G23 peptide is shown to have transcytotic capacity in brain endothelial cells in vitro, as well as a brain-targeting potential in vivo, as reflected by the accumulation of G23-polymersomes in the brain in vivo at a level comparable to that of RI7217-polymersomes, which are targeted toward the transferrin receptor. Thus the G23 peptide seems to serve both of the requirements that are needed for efficient brain drug delivery of nanocarriers. An unexpected finding was the efficient accumulation of G23-polymersomes in lung. In conclusion, because of its combined brain-targeting and transcytotic capacity, the G23 peptide could be useful in the development of targeted nanocarriers for drug delivery into the brain, but appears especially attractive for specific drug delivery to the lung. PMID:22536790

Stojanov, Katica; Georgieva, Julia V; Brinkhuis, René P; van Hest, Jan C; Rutjes, Floris P; Dierckx, Rudi A J O; de Vries, Erik F J; Zuhorn, Inge S

2012-06-01

81

Identification of flanking SSR markers for a major rice gall midge resistance gene Gm1 and their validation  

Microsoft Academic Search

Host-plant resistance is the preferred strategy for management of Asian rice gall midge ( Orseolia oryzae), a serious pest in many rice-growing countries. The deployment of molecular markers linked to gall midge resistance genes in breeding programmes can accelerate the development of resistant cultivars. In the present study, we have tagged and mapped a dominant gall midge resistance gene, Gm1,

S. K. Biradar; R. M. Sundaram; T. Thirumurugan; J. S. Bentur; S. Amudhan; V. V. Shenoy; B. Mishra; J. Bennett; N. P. Sarma

2004-01-01

82

Role of Lipid Rafts and GM1 in the Segregation and Processing of Prion Protein  

PubMed Central

The prion protein (PrPC) is highly expressed within the nervous system. Similar to other GPI-anchored proteins, PrPC is found in lipid rafts, membrane domains enriched in cholesterol and sphingolipids. PrPC raft association, together with raft lipid composition, appears essential for the conversion of PrPC into the scrapie isoform PrPSc, and the development of prion disease. Controversial findings were reported on the nature of PrPC-containing rafts, as well as on the distribution of PrPC between rafts and non-raft membranes. We investigated PrPC/ganglioside relationships and their influence on PrPC localization in a neuronal cellular model, cerebellar granule cells. Our findings argue that in these cells at least two PrPC conformations coexist: in lipid rafts PrPC is present in the native folding (?-helical), stabilized by chemico-physical condition, while it is mainly present in other membrane compartments in a PrPSc-like conformation. We verified, by means of antibody reactivity and circular dichroism spectroscopy, that changes in lipid raft-ganglioside content alters PrPC conformation and interaction with lipid bilayers, without modifying PrPC distribution or cleavage. Our data provide new insights into the cellular mechanism of prion conversion and suggest that GM1-prion protein interaction at the cell surface could play a significant role in the mechanism predisposing to pathology. PMID:24859148

Botto, Laura; Cunati, Diana; Coco, Silvia; Sesana, Silvia; Bulbarelli, Alessandra; Biasini, Emiliano; Colombo, Laura; Negro, Alessandro; Chiesa, Roberto; Masserini, Massimo; Palestini, Paola

2014-01-01

83

Differential uPAR recruitment in caveolar-lipid rafts by GM1 and GM3 gangliosides regulates endothelial progenitor cells angiogenesis  

PubMed Central

Gangliosides and the urokinase plasminogen activator receptor (uPAR) tipically partition in specialized membrane microdomains called lipid-rafts. uPAR becomes functionally important in fostering angiogenesis in endothelial progenitor cells (EPCs) upon recruitment in caveolar-lipid rafts. Moreover, cell membrane enrichment with exogenous GM1 ganglioside is pro-angiogenic and opposite to the activity of GM3 ganglioside. On these basis, we first checked the interaction of uPAR with membrane models enriched with GM1 or GM3, relying on the adoption of solid-supported mobile bilayer lipid membranes with raft-like composition formed onto solid hydrophilic surfaces, and evaluated by surface plasmon resonance (SPR) the extent of uPAR recruitment. We estimated the apparent dissociation constants of uPAR-GM1/GM3 complexes. These preliminary observations, indicating that uPAR binds preferentially to GM1-enriched biomimetic membranes, were validated by identifying a pro-angiogenic activity of GM1-enriched EPCs, based on GM1-dependent uPAR recruitment in caveolar rafts. We have observed that addition of GM1 to EPCs culture medium promotes matrigel invasion and capillary morphogenesis, as opposed to the anti-angiogenesis activity of GM3. Moreover, GM1 also stimulates MAPKinases signalling pathways, typically associated with an angiogenesis program. Caveolar-raft isolation and Western blotting of uPAR showed that GM1 promotes caveolar-raft partitioning of uPAR, as opposed to control and GM3-challenged EPCs. By confocal microscopy, we have shown that in EPCs uPAR is present on the surface in at least three compartments, respectively, associated to GM1, GM3 and caveolar rafts. Following GM1 exogenous addition, the GM3 compartment is depleted of uPAR which is recruited within caveolar rafts thereby triggering angiogenesis. PMID:25313007

Margheri, Francesca; Papucci, Laura; Schiavone, Nicola; D'Agostino, Riccardo; Trigari, Silvana; Serratì, Simona; Laurenzana, Anna; Biagioni, Alessio; Luciani, Cristina; Chillà, Anastasia; Andreucci, Elena; Del Rosso, Tommaso; Margheri, Giancarlo; Del Rosso, Mario; Fibbi, Gabriella

2015-01-01

84

GM1 ganglioside reduces the motor incoordination and loss of righting reflex caused by acute ethanol in C57BL/6J mice  

SciTech Connect

Ethanol produces its intoxicating effects by modifying neuronal membranes. Gangliosides stabilize neuronal membranes and promote their recovery from a variety of insults. In this experiment, the efficacy of GM1(i.p.) to reverse ethanol intoxication was evaluated in male mice trained to run on a constantly accelerating rotorod. When mice were tested 15-min following saline or ethanol GM1 pre-treatment reduced rotorod performance by 15% but was ineffective in modifying the ethanol-impaired performance. However, when mice were tested at 15, 35, 55, 75, and 95 min intervals following ethanol, GM1 pre-treatments dose-dependently reduced the efficacy and duration of ethanol in producing motor incoordination. Further, GM1 given prior to ethanol significantly prolonged the time to onset of the loss of righting reflex from 1.4 to 1.9 min, and reduced the duration of the righting-reflex loss from 94 to 77 min. This GM1 effect was seen at 24 h, but not at 48 or 72 h after its administration. The blood ethanol concentration at awakening was significantly higher in 24h GM1-treated animals than in controls suggesting that the GM1 effect was not due to an alteration in ethanol clearance. These findings support the hypothesis that GM1 promotes recovery from ethanol intoxication via a neuroprotective mechanism.

Wallis, C.; Rezazadeh, S.M.; Forster, M.J.; Lal, H. (Texas Coll. of Osteopathic Medicine, Ft. Worth (United States))

1992-02-26

85

CD4 ligation excludes the Carma1-Bcl10-MALT1 complex from GM1-positive membrane rafts in CD3/CD28 activated T cells  

E-print Network

1 CD4 ligation excludes the Carma1-Bcl10-MALT1 complex from GM1-positive membrane rafts in CD3/CD28 protein1, CDC= complement-dependent cytotoxicity, EGFP= enhance green fluorescent protein, GM1= ganglioside M1, IL-2= interleukin 2, PKC= protein kinase C, MAGUK= membrane-associated guanylate kinase , MALT

Boyer, Edmond

86

Cholesterol accelerates the binding of Alzheimer's ?-amyloid peptide to ganglioside GM1 through a universal hydrogen-bond-dependent sterol tuning of glycolipid conformation  

PubMed Central

Age-related alterations of membrane lipids in brain cell membranes together with high blood cholesterol are considered as major risk factors for Alzheimer's disease. Yet the molecular mechanisms by which these factors increase Alzheimer's risk are mostly unknown. In lipid raft domains of the plasma membrane, neurotoxic Alzheimer's beta-amyloid (Abeta) peptides interact with both cholesterol and ganglioside GM1. Recent data also suggested that cholesterol could stimulate the binding of Abeta to GM1 through conformational modulation of the ganglioside headgroup. Here we used a combination of physicochemical and molecular modeling approaches to decipher the mechanisms of cholesterol-assisted binding of Abeta to GM1. With the aim of decoupling the effect of cholesterol on GM1 from direct Abeta-cholesterol interactions, we designed a minimal peptide (Abeta5-16) containing the GM1-binding domain but lacking the amino acid residues involved in cholesterol recognition. Using the Langmuir technique, we showed that cholesterol (but not phosphatidylcholine or sphingomyelin) significantly accelerates the interaction of Abeta5-16 with GM1. Molecular dynamics simulations suggested that Abeta5-16 interacts with a cholesterol-stabilized dimer of GM1. The main structural effect of cholesterol is to establish a hydrogen-bond between its own OH group and the glycosidic-bond linking ceramide to the glycone part of GM1, thereby inducing a tilt in the glycolipid headgroup. This fine conformational tuning stabilizes the active conformation of the GM1 dimer whose headgroups, oriented in two opposite directions, form a chalice-shaped receptacle for Abeta. These data give new mechanistic insights into the stimulatory effect of cholesterol on Abeta/GM1 interactions. They also support the emerging concept that cholesterol is a universal modulator of protein-glycolipid interactions in the broader context of membrane recognition processes. PMID:23772214

Fantini, Jacques; Yahi, Nouara; Garmy, Nicolas

2013-01-01

87

Cholesterol accelerates the binding of Alzheimer's ?-amyloid peptide to ganglioside GM1 through a universal hydrogen-bond-dependent sterol tuning of glycolipid conformation.  

PubMed

Age-related alterations of membrane lipids in brain cell membranes together with high blood cholesterol are considered as major risk factors for Alzheimer's disease. Yet the molecular mechanisms by which these factors increase Alzheimer's risk are mostly unknown. In lipid raft domains of the plasma membrane, neurotoxic Alzheimer's beta-amyloid (Abeta) peptides interact with both cholesterol and ganglioside GM1. Recent data also suggested that cholesterol could stimulate the binding of Abeta to GM1 through conformational modulation of the ganglioside headgroup. Here we used a combination of physicochemical and molecular modeling approaches to decipher the mechanisms of cholesterol-assisted binding of Abeta to GM1. With the aim of decoupling the effect of cholesterol on GM1 from direct Abeta-cholesterol interactions, we designed a minimal peptide (Abeta5-16) containing the GM1-binding domain but lacking the amino acid residues involved in cholesterol recognition. Using the Langmuir technique, we showed that cholesterol (but not phosphatidylcholine or sphingomyelin) significantly accelerates the interaction of Abeta5-16 with GM1. Molecular dynamics simulations suggested that Abeta5-16 interacts with a cholesterol-stabilized dimer of GM1. The main structural effect of cholesterol is to establish a hydrogen-bond between its own OH group and the glycosidic-bond linking ceramide to the glycone part of GM1, thereby inducing a tilt in the glycolipid headgroup. This fine conformational tuning stabilizes the active conformation of the GM1 dimer whose headgroups, oriented in two opposite directions, form a chalice-shaped receptacle for Abeta. These data give new mechanistic insights into the stimulatory effect of cholesterol on Abeta/GM1 interactions. They also support the emerging concept that cholesterol is a universal modulator of protein-glycolipid interactions in the broader context of membrane recognition processes. PMID:23772214

Fantini, Jacques; Yahi, Nouara; Garmy, Nicolas

2013-01-01

88

Evaluating impact level of different factors in environmental impact assessment for incinerator plants using GM (1, N) model.  

PubMed

In this study, the impact levels in environmental impact assessment (EIA) reports of 10 incinerator plants were quantified and discussed. The relationship between the quantified impact levels and the plant scale factors of BeiTou, LiZe, BaLi, LuTsao, RenWu, PingTung, SiJhou and HsinChu were constructed, and the impact levels of the GangShan (GS) and YongKong (YK) plants were predicted using grey model GM (1, N). Finally, the effects of plant scale factors on impact levels were evaluated using grey model GM (1, N) too. According to the predicted results of GM, the relative errors of topography/geology/soil, air quality, hydrology/water quality, solid waste, noise, terrestrial fauna/flora, aquatic fauna/flora and traffic in the GS plant were 17%, 14%, 15%, 17%, 75%, 16%, 13%, and 37%, respectively. The relative errors of the same environmental items in the YK plant were 1%, 18%, 10%, 40%, 37%, 3%, 25% and 33%, respectively. According to GM (1, N), design capacity (DC) and heat value (HV) were the plant scale factors that affected the impact levels significantly in each environmental item, and thus were the most significant plant scale factors. GM (1, N) was effective in predicting the environmental impact and analyzing the reasonableness of the impact. If there is an EIA for a new incinerator plant to be reviewed in the future, the official committee of the Taiwan EPA could review the reasonableness of impact levels in EIA reports quickly. PMID:17919897

Pai, T Y; Chiou, R J; Wen, H H

2008-01-01

89

Anti-Asialo GM1 NK Cell Depleting Antibody Does Not Alter the Development of Bleomycin Induced Pulmonary Fibrosis  

PubMed Central

Despite circumstantial evidence postulating a protective role for NK cells in many fibrotic conditions, their contribution to the development of pulmonary fibrosis has yet to be tested. Lung-migrating NK cells are thought to attenuate the development of bleomycin induced pulmonary fibrosis (BIPF) by providing anti-fibrotic mediators and cytokines, such as IFN-?. If true, we reasoned that depletion of NK cells during experimentally-induced fibrotic disease would lead to exacerbated fibrosis. To test this, we treated mice with NK cell-depleting antisera (anti-asialo GM1) and evaluated lung inflammation and fibrosis in the BIPF model. While NK cell infiltration into the airways was maximal at day 10 after bleomycin injection, NK cells represented a minor portion (1–3%) of the total leukocytes in BAL fluid. Anti-asialo GM1 significantly abrogated NK cell numbers over the course of the disease. Depletion of NK cells with anti-asialo GM1 before and throughout the BIPF model, or during just the fibrotic phase did not alter fibrosis development or affect the levels of any of the pro-inflammatory/pro-fibrotic cytokines measured (IL-1?, IL-17, IFN-?, TGF-? and TNF-?). In addition, adoptively transferred NK cells, which were detectable systemically and in the airways throughout BIPF, failed to impact lung fibrosis. These findings indicate that NK cells likely do not play an essential protective role in controlling pulmonary fibrosis development. PMID:24922516

Monnier, Justin; Zabel, Brian A.

2014-01-01

90

Identification of flanking SSR markers for a major rice gall midge resistance gene Gm1 and their validation.  

PubMed

Host-plant resistance is the preferred strategy for management of Asian rice gall midge (Orseolia oryzae), a serious pest in many rice-growing countries. The deployment of molecular markers linked to gall midge resistance genes in breeding programmes can accelerate the development of resistant cultivars. In the present study, we have tagged and mapped a dominant gall midge resistance gene, Gm1, from the Oryza sativa cv. W1263 on chromosome 9, using SSR markers. A progeny-tested F2 mapping population derived from the cross W1263/TN1 was used for analysis. To map the gene locus, initially a subset of the F2 mapping population consisting of 20 homozygous resistant and susceptible lines each was screened with 63 parental polymorphic SSR markers. The SSR markers RM316, RM444 and RM219, located on chromosome 9, are linked to Gm1 at genetic distances of 8.0, 4.9 and 5.9 cM, respectively, and flank the gene locus. Further, gene/marker order was also determined. The utility of the co-segregating SSR markers was tested in a backcross population derived from the cross Swarna/W1263//Swarna, and allelic profiles of these markers were analysed in a set of donor rice genotypes possessing Gm1 and in a few gall midge-susceptible, elite rice varieties. PMID:15278284

Biradar, S K; Sundaram, R M; Thirumurugan, T; Bentur, J S; Amudhan, S; Shenoy, V V; Mishra, B; Bennett, J; Sarma, N P

2004-11-01

91

Conformation of the oligosaccharide chain of G(M1) ganglioside in a carbohydrate-enriched surface.  

PubMed Central

The solution structure of ganglioside G(M1) carbohydrate moiety at the surface of a 102-kDa lipid-modified-G(M1) micelle is investigated by high-resolution 1H-NMR in H2O. The micellar surface can be considered a cluster-like lateral distribution of the gangliosides, each single monomer being anchored in a carbohydrate-enriched model membrane matrix. 1H NOESY measurements at short mixing times reveal a rigid trisaccharide core -beta-GalNAc-(1-4)-[alpha-Neu5Ac-(2-3)]-beta-Gal- and a more flexible beta-Gal-(1-3)-beta-GalNAc- terminal glycosidic bond. In the lipid-modified G(M1) ganglioside micellar system, there is no evidence that intermolecular side-by-side carbohydrate interactions modulate, or alter in any way, the head-group spatial arrangement. Possible intermonomer interactions at the level of the branched trisaccharide portion were further investigated on mixed micelles of natural N-glycolyl- and N-acetylneuraminic acid containing G(M1) in D2O, taking advantage of the different NMR features of N-glycolyl- and N-acetylneuraminic acids, which allow discrimination between sialic acid ring proton signals. Measurements of the water/ganglioside-OH proton chemical exchange rates suggest hydroxyl group involvement at position 8 of sialic acid in strong intramolecular interaction processes. PMID:9449331

Brocca, P; Berthault, P; Sonnino, S

1998-01-01

92

Naturally occurring GM2 gangliosidosis in two Muntjak deer with pathological and biochemical features of human classical Tay-Sachs disease (type B GM2 gangliosidosis).  

PubMed

Two juvenile sibling male Muntjak deer (Muntiacus muntjak) with histories of depression, ataxia, circling and visual deficits were studied. Cerebrospinal fluid analyses revealed vacuolated macrophages that contained long parallel needle-like intracytoplasmic inclusions. Light microscopically, nerve cell bodies throughout the brain, ganglion cells within the retina and neurons in the myenteric plexuses were variably swollen and had pale granular to finely vacuolated eosinophilic cytoplasm. Neuronal cytoplasm stained specifically with sudan black and Luxolfast blue stains. Within the brain there were occasional axonal spheroids, foci of astrogliosis and scattered microglial cells with abundant pale foamy cytoplasm. Electron microscopy of the brain and retina revealed numerous neurons and ganglion cells, respectively, with multiple membrane-bound structures that contained compact electron-dense membranous whorls and fewer parallel membranous stacks. Thin layer chromatography of total lipid extracts of the cerebral cortex of both cases revealed massive accumulation of G(M2) ganglioside. Crude kidney extracts of the two affected deer were able to hydrolyze 4-methylumbelliferyl beta-GlcNAc, but not 4-methylumbelliferyl beta-GlcNAc-6-sulfate, indicating the defect of beta-hexosaminidase A. Cellogel electrophoresis of the kidney extracts also revealed the deficiency of beta-hexosaminidase A in the two deer. It is concluded that these two deer had the biochemical lesion identical to that of human type B G(M2) gangliosidosis (classical Tay-Sachs disease). PMID:9930895

Fox, J; Li, Y T; Dawson, G; Alleman, A; Johnsrude, J; Schumacher, J; Homer, B

1999-01-01

93

Late onset GM2 gangliosidosis mimicking spinal muscular atrophy.  

PubMed

A case of late onset GM2 gangliosidodis with spinal muscular atrophy phenotype followed by cerebellar and extrapyramidal symptoms is presented. Genetic analysis revealed compound heterozygous mutation in exon 10 of the HEXA gene. Patient has normal intelligence and emotional reactivity. Neuroimaging tests of the brain showed only cerebellar atrophy consistent with MR spectroscopy (MRS) abnormalities. (18)F-fluorodeoxyglucose positron emission tomography (18)F-FDG PET/CT of the brain revealed glucose hypometabolism in cerebellum and in temporal and occipital lobes bilaterally. PMID:23820084

Jamrozik, Z; Lugowska, A; Go??biowski, M; Królicki, L; M?czewska, J; Ku?ma-Kozakiewicz, M

2013-09-25

94

GM2 gangliosidosis in Saudi Arabia: multiple mutations and considerations for future carrier screening.  

PubMed

The GM2 gangliosidose, Tay-Sachs and Sandhoff diseases, are a class of lysosomal storage diseases in which relentless neurodegeneration results in devastating neurological disability and premature death. Primary prevention is the most effective intervention since no effective therapy is currently available. An extremely successful model for the prevention of GM2 gangliosidosis in the Ashkenazi Jewish community is largely attributable to the very limited number of founder mutations in that population. Consistent with our previous observation of allelic heterogeneity in consanguineous populations, we show here that these diseases are largely caused by private mutations which present a major obstacle in replicating the Ashkenazi success story. Alternative solutions are proposed which can also be implemented for other autosomal recessive diseases in our population. PMID:21567908

Kaya, Namik; Al-Owain, Mohammad; Abudheim, Nada; Al-Zahrani, Jawaher; Colak, Dilek; Al-Sayed, Moeen; Milanlioglu, Aysel; Ozand, Pinar T; Alkuraya, Fowzan S

2011-06-01

95

A Trp474Cys mutation in the alpha-subunit of beta-hexosaminidase causes a subacute encephalopathic form of G{sub M2} gangliosidosis, type 1  

SciTech Connect

Mutations in the HEXA gene that encodes the {alpha}-subunit of the heterodimeric lysosomal enzyme {beta}-hexosaminidase A, or Hex A ({alpha}{beta}), cause G{sub M2} gangliosidosis, type 1. The infantile form (Tay-Sachs disease) results when there is no residual Hex A activity, while less severe and more variable clinical phenotypes result when residual Hex A activity is present. A non-Jewish male who presented with an acute psychotic episode at age 16 was diagnosed with a subacute encephalopathic form of G{sub M2} gangliosidosis. At age 19, chronic psychosis with intermittent acute exacerbations remains the most disabling symptom in this patient and his affected brother although both exhibit some ataxia and moderately severe dysarthria. We have found a 4 bp insertion (+TATC 1278) associated with infantile Tay-Sachs disease on one allele; no previously identified mutation was found on the second allele. SSCP analysis detected a shift in exon 13 and sequencing revealed a G1422C mutation in the second allele that results in a Trp474Cys substitution. The presence of the mutation was confirmed by the loss of HaeIII and ScrFI sites in exon 13 PCR products from the subjects and their father. The mutation was introduced into the {alpha}-subunit cDNA and Hex S ({alpha}{alpha}) and Hex A ({alpha}{beta}) were transiently expressed in monkey COS-7 cells. The Trp474Cys mutant protein had approximately 5% and 12% of wild-type Hex S and Hex A activity, respectively. Western blot analysis revealed a small amount of residual mature {alpha}-subunit and a normal level of precursor protein. We conclude that the Trp474Cys mutation is the cause of the Hex A deficiency associated with a subacute (juvenile-onset) phenotype in this patient. Like other mutations in exon 13 of HEXA, it appears to affect intracellular processing. Studies of the defect in intracellular processing are in progress.

Petroulakis, E.; Cao, Z.; Salo, T. [Univ. of Manitoba, Winnipeg (Canada)] [and others

1994-09-01

96

[Molecular pathogenesis and therapeutic approach of GM2 gangliosidosis].  

PubMed

Tay-Sachs and Sandhoff diseases (GM2 gangliosidoses) are autosomal recessive lysosomal storage diseases caused by gene mutations in HEXA and HEXB, each encoding human lysosomal ?-hexosaminidase ?-subunits and ?-subunits, respectively. In Tay-Sachs disease, excessive accumulation of GM2 ganglioside (GM2), mainly in the central nervous system, is caused by a deficiency of the HexA isozyme (?? heterodimer), resulting in progressive neurologic disorders. In Sandhoff disease, combined deficiencies of HexA and HexB (?? homodimer) cause not only the accumulation of GM2 but also of oligosaccharides carrying terminal N-acetylhexosamine residues (GlcNAc-oligosaccharides), resulting in systemic manifestations including hepatosplenomegaly as well as neurologic symptoms. Hence there is little clinically effective treatment for these GM2 gangliosidoses. Recent studies on the molecular pathogenesis in Sandhoff disease patients and disease model mice have shown the involvement of microglial activation and chemokine induction in neuroinflammation and neurodegeneration in this disease. Experimental and therapeutic approaches, including recombinant enzyme replacement, have been performed using Sandhoff disease model mice, suggesting the future application of novel techniques to treat GM2 gangliosidoses (Hex deficiencies), including Sandhoff disease as well as Tay-Sachs disease. In this study, we isolated astrocytes and microglia from the neonatal brain of Sandhoff disease model mice and demonstrated abnormalities of glial cells. Moreover, we demonstrated the therapeutic effect of an intracerebroventricular administration of novel recombinant human HexA carrying a high content of M6P residue in Sandhoff disease model mice. PMID:23370522

Tsuji, Daisuke

2013-01-01

97

GM2 gangliosidosis associated with a HEXA missense mutation in Japanese Chin dogs: a potential model for Tay Sachs disease.  

PubMed

GM2 gangliosidosis is a fatal lysosomal storage disease caused by a deficiency of ?-hexosaminidase (EC 3.2.1.52). There are two major isoforms of the enzyme: hexosaminidase A composed of an ? and a ? subunit (encoded by HEXA and HEXB genes, respectively); and, hexosaminidase B composed of two ? subunits. Hexosaminidase A requires an activator protein encoded by GM2A to catabolize GM2 ganglioside, but even in the absence of the activator protein, it can hydrolyze the synthetic substrates commonly used to assess enzyme activity. GM2 gangliosidosis has been reported in Japanese Chin dogs, and we identified the disease in two related Japanese Chin dogs based on clinical signs, histopathology and elevated brain GM2 gangliosides. As in previous reports, we found normal or elevated hexosaminidase activity when measured with the synthetic substrates. This suggested that the canine disease is analogous to human AB variant of G(M2) gangliosidosis, which results from mutations in GM2A. However, only common neutral single nucleotide polymorphisms were found upon sequence analysis of the canine ortholog of GM2A from the affected Japanese Chins. When the same DNA samples were used to sequence HEXA, we identified a homozygous HEXA:c967G>A transition which predicts a p.E323K substitution. The glutamyl moiety at 323 is known to make an essential contribution to the active site of hexosaminidase A, and none of the 128 normal Japanese Chins and 92 normal dogs of other breeds that we tested was homozygous for HEXA:c967A. Thus it appears that the HEXA:c967G>A transition is responsible for the GM2 gangliosidosis in Japanese Chins. PMID:23266199

Sanders, Douglas N; Zeng, Rong; Wenger, David A; Johnson, Gary S; Johnson, Gayle C; Decker, Jared E; Katz, Martin L; Platt, Simon R; O'Brien, Dennis P

2013-01-01

98

The Mutations in Ashkenazi Jews with Adult GM2 Gangliosidosis, the Adult Form of Tay-Sachs Disease  

Microsoft Academic Search

The adult form of Tay-Sachs disease, adult GM2 gangliosidosis, is an autosomal recessive disorder that results from mutations in the alpha chain of beta -hexosaminidase A. This disorder, like infantile Tay-Sachs disease, is more frequent in the Ashkenazi Jewish population. A point mutation in the alpha -chain gene was identified that results in the substitution of Gly269 with Ser in

Ruth Navon; Richard L. Proia

1989-01-01

99

N-Alpha-Acetylation of ?-Synuclein Increases Its Helical Folding Propensity, GM1 Binding Specificity and Resistance to Aggregation  

PubMed Central

A switch in the conformational properties of ?-synuclein (?S) is hypothesized to be a key step in the pathogenic mechanism of Parkinson’s disease (PD). Whereas the beta-sheet-rich state of ?S has long been associated with its pathological aggregation in PD, a partially alpha-helical state was found to be related to physiological lipid binding; this suggests a potential role of the alpha-helical state in controlling synaptic vesicle cycling and resistance to ?-sheet rich aggregation. N-terminal acetylation is the predominant post-translational modification of mammalian ?S. Using circular dichroism, isothermal titration calorimetry, and fluorescence spectroscopy, we have analyzed the effects of N-terminal acetylation on the propensity of recombinant human ?S to form the two conformational states in interaction with lipid membranes. Small unilamellar vesicles of negatively charged lipids served as model membranes. Consistent with previous NMR studies using phosphatidylserine, we found that membrane-induced ?-helical folding was enhanced by N-terminal acetylation and that greater exothermic heat could be measured upon vesicle binding of the modified protein. Interestingly, the folding and lipid binding enhancements with phosphatidylserine in vitro were weak when compared to that of ?S with GM1, a lipid enriched in presynaptic membranes. The resultant increase in helical folding propensity of N-acetylated ?S enhanced its resistance to aggregation. Our findings demonstrate the significance of the extreme N-terminus for folding nucleation, for relative GM1 specificity of ?S-membrane interaction, and for a protective function of N-terminal-acetylation against ?S aggregation mediated by GM1. PMID:25075858

Bartels, Tim; Kim, Nora C.; Luth, Eric S.; Selkoe, Dennis J.

2014-01-01

100

Endocytosis of cholera toxin in GERL-like structures of murine neuroblastoma cells pretreated with GM1 ganglioside. Cholera toxin internalization into Neuroblastoma GERL  

PubMed Central

Cholera toxin (CT), covalently attached to horseradish peroxidase (HRP), is a specific cytochemical marker for GM1 ganglioside (GM1) and retains the ability of the native toxin to raise levels of cyclic AMP in avian erythrocytes. Using a cytochemical stain for HRP, we found that 9% of control cultured murine neuroblastoma cells bound cholera toxin-horseradish peroxidase conjugates (CT-HRP) on their surfaces after incubations for 1 h at 4 degrees C. Exogenous GM1, the natural receptor of CT, becomes associated in the culture medium with the plasma membranes of these cells so that 96% of cells are stained. Cells preincubated with GM1 at 4 degrees C were exposed to CT-HRP for 1 h at 4 degrees C. After washing, cells were incubated at 37 degrees C for 30 min-24 h. Endocytosis of CT-HRP occurred within 30 min and CT-HRP remained, throughout the 24-h period, in tubules, vesicles, and cisternae often found near the Golgi apparatus; this aggregate of peroxidase-positive elements probably corresponds to Golgi apparatus- endoplasmic reticulum-lysosomes (GERL) of neurons. In metaphase cells, CT-HRP was observed in aggregates of vesicles and tubules clustered near the centriole. Conjugates of HRP with subunit B, the GM1 binding component of CT, were internalized by cells pretreated with GM1 as was CT-HRP. The 9% of neuroblastoma cells binding CT-HRP in the absence of exogenous GM1 internalized the ligand in a manner indistinguishable from that of the treated cells. These findings indicate that, in neuroblastoma cells, a system of vesicles, tubules, and cisternae, analogous to GERL of neurons, is the primary recipient of adsorptive endocytosis of CT bound to endogenous or exogenously introduced GM1. PMID:457774

1979-01-01

101

Leptin inhibits amyloid ?-protein fibrillogenesis by decreasing GM1 gangliosides on the neuronal cell surface through PI3K/Akt/mTOR pathway.  

PubMed

Leptin is a centrally acting hormone that controls metabolic pathways. Recent epidemiological studies suggest that plasma leptin is protective against Alzheimer's disease. However, the mechanism that underlies this effect remains uncertain. To investigate whether leptin inhibits the assembly of amyloid ?-protein (A?) on the cell surface of neurons, we treated primary neurons with leptin. Leptin treatment decreased the GM1 ganglioside (GM1) levels in the detergent-resistant membrane microdomains (DRMs) of neurons. The increase in GM1 expression induced by leptin was inhibited after pre-treatment with inhibitors of phosphatidylinositol 3-kinase (LY294002), Akt (triciribine) and the mammalian target of rapamycin (i.e. rapamycin), but not by an inhibitor of extracellular signal-regulated kinase (PD98059). In addition, pre-treatment with these reagents blocked the induction of GM1 in DRMs by leptin. Furthermore, A? assembly on the cell surface of neurons was inhibited greatly after treatment with leptin. This reduction was markedly inhibited after pre-treatment with LY294002, triciribine, and rapamycin. These results suggest that leptin significantly inhibits A? assembly by decreasing GM1 expression in DRMs of the neuronal surface through the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin pathway. These findings highlight the importance of understanding the function of leptin in AD brains. In this study, our aim was to determine whether leptin regulates the expression and localization of GM1 on the neuronal membrane and if it induces the formation of A? assembly on the cell surface of neurons. Our results suggest that leptin regulates the expression of GM1 in DRMs of the neuronal membranes. Moreover, leptin does not seem to facilitate fibrillogenesis of exogenously added soluble A? from the cell surface of neurons. PMID:25039425

Yamamoto, Naoki; Tanida, Mamoru; Kasahara, Rika; Sobue, Kazuya; Suzuki, Kenji

2014-11-01

102

Neurotropin promotes NGF signaling through interaction of GM1 ganglioside with Trk neurotrophin receptor in PC12 cells.  

PubMed

Activation of the high-affinity nerve growth factor (NGF) receptor Trk occurs through multiple processes consisted of translocation and clustering within the plasma membrane lipid rafts, dimerization and autophosphorylation. Here we found that a nonprotein extract of inflamed rabbit skin inoculated with vaccinia virus (Neurotropin(®)) enhanced efficiency of NGF signaling. In rat pheochromocytoma PC12 cells overexpressing Trk (PCtrk cells), Neurotropin augmented insufficient neurite outgrowth observed at suboptimal concentration of NGF (2ng/mL) in a manner depending on Trk kinase activity. Cellular exposure to Neurotropin resulted in an accumulation of Trk-GM1 complexes without affecting dimerization or phosphorylation states of Trk. Following NGF stimulation, Neurotropin significantly facilitated the time course of NGF-induced Trk autophosphorylation. These observations provide a unique mechanism controlling efficiency of NGF signaling, and raise the therapeutic potential of Neurotropin for various neurological conditions associated with neurotrophin dysfunction. PMID:25454796

Fukuda, Yu; Fukui, Takao; Hikichi, Chika; Ishikawa, Tomomasa; Murate, Kenichiro; Adachi, Takeshi; Imai, Hideki; Fukuhara, Koki; Ueda, Akihiro; Kaplan, Allen P; Mutoh, Tatsuro

2015-01-30

103

Selection of Escherichia coli heat-labile toxin (LT) inhibitors using both the GM1-ELISA and the cAMP vero cell assay.  

PubMed

Weaned piglets are very susceptible to diarrhea caused by enterotoxigenic Escherichia coli. In the past, various natural components were proposed to have beneficial effects by reducing the effects of diarrheal infectious diseases in humans and animals, and thus may represent an alternative for the use of (prophylactic) antibiotics. Alternatives may inactivate enterotoxigenic Escherichia coli heat-labile toxin (LT) by interfering with toxin binding to the cellular receptor GM1. In this study, various plants and other natural substances were tested for inhibitory properties, in the GM1 binding assay, and in the LT-induced cAMP production in Vero cells. The toxic dose of each compound was determined in a cell viability assay, and the highest nontoxic concentrations were used in the GM1 and cAMP assays. Results demonstrated that only d-(+)-galactose, lactose, N-acetyl-d-galactosamine, and two tea extracts were able to inhibit the binding of LT to its GM1 receptor. In the cAMP assay, only the two tea extracts showed inhibitory activity. This shows that d-(+)-galactose, lactose, and N-acetyl-d-galactosamine can indeed inhibit LT binding to GM1 based on structural homology with GM1 in the absence of living cells. However, in the cAMP assay, d-(+)-galactose, and lactose, N-acetyl-d-galactosamine are apparently metabolized to below their effective inhibitory concentration, likely predicting limited practical applicability in vivo. Both tea extracts maintained their activity in the presence of cells. The active compounds in both are probably polyphenols, which are not easily metabolized, and most likely work by aggregating the toxin. In conclusion, the combination of methods used here is a convenient and fast method for preselecting natural substances containing potentially toxin-binding compounds. Furthermore, if antidiarrhea activity is attributed to compounds found inactive here, their activity is unlikely based on interference with toxin binding. PMID:23692076

Verhelst, Roderick; Schroyen, Martine; Buys, Nadine; Niewold, Theo

2013-07-01

104

Naloxone rapidly evokes endogenous kappa opioid receptor-mediated hyperalgesia in naïve mice pretreated briefly with GM1 ganglioside or in chronic morphine-dependent mice  

Microsoft Academic Search

Low-dose naloxone-precipitated withdrawal hyperalgesia is a reliable indicator of physical dependence after chronic morphine treatment. A remarkably similar long-lasting (>3–4 h) hyperalgesia is evoked by injection of a low dose of naloxone (10 ?g\\/kg, s.c.) in naïve mice after acute pretreatment with the glycolipid, GM1 ganglioside (1 mg\\/kg) (measured by warm-water-immersion tail-flick assays). GM1 treatment markedly increases the efficacy of excitatory Gs-coupled opioid

Stanley M. Crain; Ke-Fei Shen

2007-01-01

105

Severe subacute GM2 gangliosidosis caused by an apparently silent HEXA mutation (V324V) that results in aberrant splicing and reduced HEXA mRNA.  

PubMed

We have characterized the molecular basis of beta-hexosaminidase A (HEX A) deficiency in a patient ascertained through an ophthalmologic examination that revealed cherry red spots on his retina. The absence of neurological deficit in this child until 3 3/4 years of age indicated residual HEX A must be present. Three HEXA mutations, 10T > C (S4P) and 972T > A (V324V) on the maternal allele, and 1A > T (M1L) on the paternal allele were identified. The effects of the amino acid substitutions on HEX A expressed in COS-7 cells were analyzed; as expected, no HEX A activity was associated with the M1L mutation but surprisingly, the S4P mutation resulted in 59% of the HEX A activity expressed by the wild type cDNA. The effect of the S4P change was much less than that of another HEXA mutation, G269S, associated with an adult onset form of G(M2) gangliosidosis. This indicated that the S4P change was not the cause of disease and suggested that one of the mutations on the maternal allele, 10T > C or 972T > A, had its effect at the mRNA level. This was confirmed by Northern blot analysis that showed only 7% of the normal level of HEXA mRNA in proband fibroblasts. Analysis of the residual mRNA by RT/PCR and sequencing revealed normal transcripts from both the maternal and paternal allele, as well as a low abundance aberrant transcript from the maternal allele. Sequencing of this aberrant transcript revealed a new exon 8 donor site created by the 972T > A mutation that resulted in a 17 bp deletion and destabilization of the resulting abnormal transcript. The remaining normal mRNA produced from the 972T > A allele must account for the delayed onset of clinical symptoms in this child. PMID:15108204

Wicklow, Brandy A; Ivanovich, Jennifer L; Plews, Margot M; Salo, Timothy J; Noetzel, Michael J; Lueder, Gregg T; Cartegni, Luca; Kaback, Michael M; Sandhoff, Konrad; Steiner, Robert D; Triggs-Raine, Barbara L

2004-06-01

106

Galectin-3 Protein Regulates Mobility of N-cadherin and GM1 Ganglioside at Cell-Cell Junctions of Mammary Carcinoma  

E-print Network

Galectin-3 Protein Regulates Mobility of N-cadherin and GM1 Ganglioside at Cell-Cell Junctions: Galectin-3-N-glycan binding forms a lattice that regulates cancer cell adhesion, migration, and signaling. Results: Galectin-3 destabilizes cell-cell junctions and increases junctional mobility of N

Gleeson, Joseph G.

107

Ganglioside GM1-Mediated Amyloid-beta Fibrillogenesis and Membrane Disruption Eva Y. Chi, Shelli L. Frey, and Ka Yee C. Lee*  

E-print Network

of cell membrane glycolipids, gangliosides, can mediate the fibrillogenesis and toxicity of AlzheimerVo, and A -induced disruption of the cell membrane may provide a pathway by which A exerts toxicity. Alzheimer interactions between A and GM1 in the cell membrane may provide a mechanism for A fibrillogenesis in Vi

Lee, Ka Yee C.

108

Mutational Analysis of Ganglioside GM1-Binding Ability, Pentamer Formation, and Epitopes of Cholera Toxin B (CTB) Subunits and CTB/Heat-Labile Enterotoxin B Subunit Chimeras  

PubMed Central

Variants of cholera toxin B subunit (CTB) were made by bisulfite- and oligonucleotide-directed mutagenesis of the ctxB gene. Variants were screened by a radial passive immune hemolysis assay (RPIHA) for loss of binding to sheep erythrocytes (SRBC). Variant CTBs were characterized for the formation of immunoreactive pentamers, the ability to bind ganglioside GM1 in vitro, and reactivity with a panel of monoclonal anti-CTB antibodies. Substitutions at eight positions (i.e., positions 22, 29, 36, 45, 64, 86, 93, and 100) greatly reduced the yield of immunoreactive CTB. RPIHA-negative substitution variants that formed immunoreactive pentamers were obtained for residues 12, 33, 36, 51, 52 + 54, 91, and 95. Tyrosine-12 was identified as a novel residue important for GM1 binding since, among all of the novel variants isolated with altered RPIHA phenotypes, only CTB with aspartate substituted for tyrosine at position 12 failed to bind significantly to ganglioside GM1 in vitro. In contrast, CTB variants with single substitutions for several other residues (Glu-51, Lys-91, and Ala-95) that participate in GM1 binding, based on the crystal structure of CTB and the oligosaccharide of GM1, were not appreciably altered in their ability to bind GM1 in vitro, even though they showed altered RPIHA phenotypes and did not bind to SRBC. Hybrid B genes made by fusing ctxB and the related Escherichia coli heat-labile enterotoxin eltB genes at codon 56 produced CTB variants that had 7 or 12 heat-labile enterotoxin B residue substitutions in the amino or carboxyl halves of the monomer, respectively, each of which which also bound GM1 as well as wild-type CTB. This collection of variant CTBs in which 47 of the 103 residues were substituted was used to map the epitopes of nine anti-CTB monoclonal antibodies (MAbs). Each MAb had a unique pattern of reactivity with the panel of CTB variants. Although no two of the epitopes recognized by different MAbs were identical, most of the single amino acid substitutions that altered the immunoreactivity of CTB affected more that one epitope. The tertiary structures of the epitopes of these anti-CTB MAbs are highly conformational and may involve structural elements both within and between CTB monomers. Substitution of valine for alanine at positions 10 and 46 had dramatic effects on the immunoreactivity of CTB, affecting epitopes recognized by eight or six MAbs, respectively. PMID:11854209

Jobling, Michael G.; Holmes, Randall K.

2002-01-01

109

Anti-GM1 antibodies cause complement-mediated disruption of sodium channel clusters in peripheral motor nerve fibers.  

PubMed

Voltage-gated Na+ (Na(v)) channels are highly concentrated at nodes of Ranvier in myelinated axons and facilitate rapid action potential conduction. Autoantibodies to gangliosides such as GM1 have been proposed to disrupt nodal Nav channels and lead to Guillain-Barré syndrome, an autoimmune neuropathy characterized by acute limb weakness. To test this hypothesis, we examined the molecular organization of nodes in a disease model caused by immunization with gangliosides. At the acute phase with progressing limb weakness, Na(v) channel clusters were disrupted or disappeared at abnormally lengthened nodes concomitant with deposition of IgG and complement products. Paranodal axoglial junctions, the nodal cytoskeleton, and Schwann cell microvilli, all of which stabilize Na(v) channel clusters, were also disrupted. The nodal molecules disappeared in lesions with complement deposition but no localization of macrophages. During recovery, complement deposition at nodes decreased, and Na(v) channels redistributed on both sides of affected nodes. These results suggest that Na(v) channel alterations occur as a consequence of complement-mediated disruption of interactions between axons and Schwann cells. Our findings support the idea that acute motor axonal neuropathy is a disease that specifically disrupts the nodes of Ranvier. PMID:17428969

Susuki, Keiichiro; Rasband, Matthew N; Tohyama, Koujiro; Koibuchi, Katsura; Okamoto, Saori; Funakoshi, Kei; Hirata, Koichi; Baba, Hiroko; Yuki, Nobuhiro

2007-04-11

110

A Trp474Cys mutation in the alpha-subunit of beta-hexosaminidase causes a subacute encephalopathic form of G{sub M2} gangliosidosis, type 1  

Microsoft Academic Search

Mutations in the HEXA gene that encodes the α-subunit of the heterodimeric lysosomal enzyme β-hexosaminidase A, or Hex A (αβ), cause G{sub M2} gangliosidosis, type 1. The infantile form (Tay-Sachs disease) results when there is no residual Hex A activity, while less severe and more variable clinical phenotypes result when residual Hex A activity is present. A non-Jewish male who

E. Petroulakis; Z. Cao; T. Salo

1994-01-01

111

Structural characterization of the GM1 ganglioside by infrared multiphoton dissociation, electron capture dissociation, and electron detachment dissociation electrospray ionization FT-ICR MS\\/MS  

Microsoft Academic Search

Gangliosides play important biological roles and structural characterization of both the carbohydrate and the lipid moieties\\u000a is important. The FT-ICR MS\\/MS techniques of electron capture dissociation (ECD), electron detachment dissociation (EDD),\\u000a and infrared multiphoton dissociation (IRMPD) provide extensive fragmentation of the protonated and deprotonated GM1 ganglioside.\\u000a ECD provides extensive structural information, including identification of both halves of the ceramide and

Melinda A. McFarland; Alan G. Marshall; Christopher L. Hendrickson; Carol L. Nilsson; Pam Fredman; Jan-Eric Månsson

2005-01-01

112

Selection of GM2, fucosyl GM1, globo H and polysialic acid as targets on small cell lung cancers for antibody mediated immunotherapy  

Microsoft Academic Search

Glycolipids GM2, GD2, GD3, fucosyl GM1, sialyl Lewis a (sLea) and globo H, and polysialic acid on embryonal NCAM, are cell-surface antigens expressed on small cell lung cancer (SCLC) biopsy specimens. They are all candidates for inclusion in a polyvalent, antibody-inducing vaccine or for adoptive therapy with monoclonal antibodies (mAbs) against SCLC. To identify the minimum optimal combination of target

P. O. Livingston; C. Hood; L. M. Krug; N. Warren; M. G. Kris; T. Brezicka; G. Ragupathi

2005-01-01

113

Antibody response after immunization with the gangliosides GM1, GM2, GM3, GD2 and GD3 in the mouse  

Microsoft Academic Search

The gangliosides GM2, GD2 and GD3 are differentiation antigens expressed on the cell surface of human melanomas and other cancers of neuroectodermal origin. We have compared the antibody response after vaccination with gangliosides GM1, GM2, GM3, GD2 and GD3 in the mouse. Purified gangliosides were injected subcutaneously alone or attached to Salmonella minnesota mutant R595 after pretreatment of the mice

Philip O. Livingston; Gerd Ritter; Michele Jones Calves

1989-01-01

114

Inhibition of neurite outgrowth of neuroblastoma Neuro-2a cells by cholera toxin B-subunit and anti-GM1 antibody.  

PubMed

The role of cell surface GM1 ganglioside in neurite outgrowth of Neuro-2a neuroblastoma cells was investigated by application of anti-GM1 antibody and the B subunit of cholera toxin (cholera B) to cultured cells stimulated to grow neurites in various ways. When the cells were simultaneously treated with stimulatory agent and cholera B, inhibition, as measured by percent of neurite-bearing cells, was observed with most stimuli: neuraminidase; GD1a ganglioside, retinoic acid, and low serum. However, with dibutyryl cyclic AMP the small reduction observed was not statistically significant. The inhibitory effect of cholera B on neurite outgrowth induced by low serum was dose-dependent, reaching a maximum at 200 ng/mL; 48 h after washout of cholera B the cells were released from inhibition and regrew neurites at nearly the previous rate in the presence of low serum. When the cells were exposed to stimulus for 6 h or more the inhibitory effect of subsequent addition of cholera B was reduced or eliminated; inhibition thus occurs during an early stage of neurite initiation. Anti-GM1 antibody at dilutions of 1:100-1:400 had the same inhibitory effect as cholera B with cells stimulated by GD1a or retinoic acid, whereas anti-GM2 antibody had no effect at 1:200 or 1:400; inhibition by the latter antibody at 1:100 dilution was similar to that attained with control ascites fluid. These results point to a pivotal role for cell surface GM1 in Neuro-2a differentiation induced by many (but not all) neuritogenic agents. PMID:8086037

Wu, G; Nakamura, K; Ledeen, R W

1994-01-01

115

Inhibitory receptor signals suppress ligation-induced recruitment of NKG2D to GM1-rich membrane domains at the human NK cell immune synapse.  

PubMed

NKG2D is an activating receptor expressed on all human NK cells and a subset of T cells. In cytolytic conjugates between NK cells and target cells expressing its ligand MHC class I chain-related gene A, NKG2D accumulates at the immunological synapse with GM1-rich microdomains. Furthermore, NKG2D is specifically recruited to detergent-resistant membrane fractions upon ligation. However, in the presence of a strong inhibitory stimulus, NKG2D-mediated cytotoxicity can be intercepted, and recruitment of NKG2D to the immunological synapse and detergent-resistant membrane fractions is blocked. Also, downstream phosphorylation of Vav-1 triggered by NKG2D ligation is circumvented by coengaging inhibitory receptors. Thus, we propose that one way in which inhibitory signaling can control NKG2D-mediated activation is by blocking its recruitment to GM1-rich membrane domains. The accumulation of activating NK cell receptors in GM1-rich microdomains may provide the necessary platform from which stimulatory signals can proceed. PMID:17442943

Endt, Johanna; McCann, Fiona E; Almeida, Catarina R; Urlaub, Doris; Leung, Rufina; Pende, Daniela; Davis, Daniel M; Watzl, Carsten

2007-05-01

116

GM1 and GD1a gangliosides modulate toxic and inflammatory effects of E. coli lipopolysaccharide by preventing TLR4 translocation into lipid rafts.  

PubMed

Exogenous gangliosides are known to inhibit the effects of Escherichia coli lipopolysaccharide (LPS) in different cells exhibiting a nti-inflammatory and immunosuppressive activities. The mechanisms underlying ganglioside action are not fully understood. Because LPS recognition and receptor complex formation occur in lipid rafts, and gangliosides play a key role in their maintenance, we hypothesize that protective effects of exogenous gangliosides would depend on inhibition of LPS signaling via prevention of TLR4 translocation into lipid rafts. The effect of GM1 and GD1a gangliosides on LPS-induced toxic and inflammatory reactions in PC12 cells, and in epithelial cells isolated from the frog urinary bladder, was studied. In PC12 cells, GD1a and GM1 significantly reduced the effect of LPS on the decrease of cell survival and on stimulation of reactive oxygen species production. In epithelial cells, gangliosides decreased LPS-stimulated iNOS expression, NO, and PGE2 production. Subcellular fractionation, in combination with immunoblotting, showed that pretreatment of cells with GM1, GD1a, or methyl-?-cyclodextrin, completely eliminated the effect of LPS on translocation of TLR4 into lipid rafts. The results are consistent with the hypothesis that ganglioside-induced prevention of TLR4 translocation into lipid rafts could be a mechanism of protection against LPS in various cells. PMID:25499607

Nikolaeva, Svetlana; Bayunova, Lubov; Sokolova, Tatyana; Vlasova, Yulia; Bachteeva, Vera; Avrova, Natalia; Parnova, Rimma

2015-03-01

117

Stem Cell Transplant for Inborn Errors of Metabolism  

ClinicalTrials.gov

Adrenoleukodystrophy; Metachromatic Leukodystrophy; Globoid Cell Leukodystrophy; Gaucher's Disease; Fucosidosis; Wolman Disease; Niemann-Pick Disease; Batten Disease; GM1 Gangliosidosis; Tay Sachs Disease; Sandhoff Disease

2012-11-06

118

Galectin-3 Protein Regulates Mobility of N-cadherin and GM1 Ganglioside at Cell-Cell Junctions of Mammary Carcinoma Cells*  

PubMed Central

Galectin-3 binding to cell surface glycoproteins, including branched N-glycans generated by N-acetylglucosaminyltransferase V (Mgat5) activity, forms a multivalent, heterogeneous, and dynamic lattice. This lattice has been shown to regulate integrin and receptor tyrosine kinase signaling promoting tumor cell migration. N-cadherin is a homotypic cell-cell adhesion receptor commonly overexpressed in tumor cells that contributes to cell motility. Here we show that galectin-3 and N-cadherin interact and colocalize with the lipid raft marker GM1 ganglioside in cell-cell junctions of mammary epithelial cancer cells. Disruption of the lattice by deletion of Mgat5, siRNA depletion of galectin-3, or competitive inhibition with lactose stabilizes cell-cell junctions. It also reduces, in a p120-catenin-dependent manner, the dynamic pool of junctional N-cadherin. Proteomic analysis of detergent-resistant membranes (DRMs) revealed that the galectin lattice opposes entry of many proteins into DRM rafts. N-cadherin and catenins are present in DRMs; however, their DRM distribution is not significantly affected by lattice disruption. Galectin lattice integrity increases the mobile fraction of the raft marker, GM1 ganglioside binding cholera toxin B subunit Ctb, at cell-cell contacts in a p120-catenin-independent manner, but does not affect the mobility of either Ctb-labeled GM1 or GFP-coupled N-cadherin in nonjunctional regions. Our results suggest that the galectin lattice independently enhances lateral molecular diffusion by direct interaction with specific glycoconjugates within the adherens junction. By promoting exchange between raft and non-raft microdomains as well as molecular dynamics within junction-specific raft microdomains, the lattice may enhance turnover of N-cadherin and other glycoconjugates that determine junctional stability and rates of cell migration. PMID:22846995

Boscher, Cécile; Zheng, Yu Zi; Lakshminarayan, Ramya; Johannes, Ludger; Dennis, James W.; Foster, Leonard J.; Nabi, Ivan R.

2012-01-01

119

Cloning and Expression of the Catalytic Domain from Rat Hepatoma H35 Cell GDP-Fucose:GM 1?1?2Fucosyltransferase, an Enzyme Which Is Activated during Early Stages of Chemical Carcinogenesis in Rat Liver  

Microsoft Academic Search

A ganglioside GM1-specific ?1?2fucosyltransferase is induced during the early stages of chemical carcinogenesis withN-2-acetylaminofluorene (AAF) in rat liver hepatocytes. The induction of this enzyme gives rise to the expression of a fucose-containing ganglioside with the same determinant structure as blood group B on a GM1ganglioside core. Fucoganglioside synthesis is not found in normal rat liver but is elevated in premalignant

Anne L. Sherwood; Eric H. Holmes

1998-01-01

120

Differential interactions of two local anesthetics with phospholipid membrane and nonerythroid spectrin: Localization in presence of cholesterol and ganglioside, GM1.  

PubMed

Interactions of two local anesthetics, dibucaine and tetracaine have been studied with phospholipid vesicles containing cholesterol and/or monosialogangliosides (GM1) using fluorescence spectroscopy. The fluorescence intensity of tetracaine showed a marked increase with the increasing molar ratio of the phospholipid to tetracaine, while that of dibucaine showed opposite effects. Steady state anisotropy and the wavelength of maximum emission (?max) decreased with the increasing phospholipids to tetracaine ratio. The extent of such changes in anisotropy and ?max in the presence and absence of two important components of neuronal membranes, cholesterol and GM1 indicated differential membrane localization of the two local anesthetics. To understand the intercellular mode of action of local anesthetics, we have also studied the interactions of dibucaine and tetracaine with brain spectrin which indicate differential spectrin interactions with similar binding strength. Thermodynamic parameters associated with such binding reveal that binding is favored by entropy. Tetracaine brings about distinct structural changes in spectrin compared to dibucaine, as reflected in the tryptophan mean lifetime and far-UV CD spectra. Tetracaine also exhibits a detergent-like property inducing concentration dependent decrease in spectrin anisotropy, further indicating structural changes in brain spectrin with probable implications in its anesthetic potential. PMID:25482358

Chakrabarti, Abhijit; Patra, Malay

2015-03-01

121

Carbohydrate-to-carbohydrate interactions between ?2,3-linked sialic acids on ?2 integrin subunits and asialo-GM1 underlie the bone metastatic behaviour of LNCAP-derivative C4-2B prostate cancer cells  

PubMed Central

Complex interplays among proteins, lipids and carbohydrates can alter the phenotype and are suggested to have a crucial role in tumour metastasis. Our previous studies indicated that a complex of the GSLs (glycosphingolipids), AsGM1 (asialo-GM1), which lacks ?2,3-linked sialic acid, and ?2?1 integrin receptors is responsible for the metastatic behaviour of C4-2B prostate cancer cells. Herein, we identified and addressed the functional significance of changes in sialylation during prostate cancer progression. We observed an increase in ?2,3-linked sialic acid residues on ?2 subunits of ?2?1 integrin receptors, correlating with increased gene expression of ?2,3-STs (sialyltransferases), particularly ST3GAL3. Cell surface ?2,3-sialylation of ?2 subunits was required for the integrin ?2?1-dependent cell adhesion to collagen type I and the same ?2,3-linked sialic acid residues on the integrin receptor were responsible for the interaction with the carbohydrate moiety of AsGM1, explaining the complex formation between AsGM1 and ?2?1 integrin receptors. These results provide novel insights into the role of sialic acids in the organization and function of important membrane components in invasion and metastatic processes. PMID:25137483

Van Slambrouck, Séverine; Groux-Degroote, Sophie; Krzewinski-Recchi, Marie-Ange; Cazet, Aurélie; Delannoy, Philippe; Steelant, Wim F. A.

2014-01-01

122

EXPERIENTIAL FACTORS IN THE EXPRESSION OF HYPERMOTILITY PRODUCED BY INTRADENTATE COLCHICINE: LACK OF EFFECT OF GM1 GANGLIOSIDE ON COLCHICINE-INDUCED LOSS OF GRANULE CELLS AND MOSSY FIBERS (JOURNAL VERSION)  

EPA Science Inventory

Adult, male Fischer-344 rats were given bilateral injections of 2.5 microgram colchicine or artificial cerebrospinal fluid into caudal and rostral sites of the dentate gyrus of the hippocampus. One group of rats received 21 consecutive daily injections of 20 mg/kg GM1 ganglioside...

123

Chaperone therapy for GM2 gangliosidosis: effects of pyrimethamine on ?-hexosaminidase activity in Sandhoff fibroblasts.  

PubMed

Sphingolipidoses are inherited genetic diseases due to mutations in genes encoding proteins involved in the lysosomal catabolism of sphingolipids. Despite a low incidence of each individual disease, altogether, the number of patients involved is relatively high and resolutive approaches for treatment are still lacking. The chaperone therapy is one of the latest pharmacological approaches to these storage diseases. This therapy allows the mutated protein to escape its natural removal and to increase its quantity in lysosomes, thus partially restoring the metabolic functions. Sandhoff disease is an autosomal recessive inherited disorder resulting from ?-hexosaminidase deficiency and characterized by large accumulation of GM2 ganglioside in brain. No enzymatic replacement therapy is currently available, and the use of inhibitors of glycosphingolipid biosynthesis for substrate reduction therapy, although very promising, is associated with serious side effects. The chaperone pyrimethamine has been proposed as a very promising drug in those cases characterized by a residual enzyme activity. In this review, we report the effect of pyrimethamine on the recovery of ?-hexosaminidase activity in cultured fibroblasts from Sandhoff patients. PMID:24356898

Chiricozzi, Elena; Niemir, Natalia; Aureli, Massimo; Magini, Alessandro; Loberto, Nicoletta; Prinetti, Alessandro; Bassi, Rosaria; Polchi, Alice; Emiliani, Carla; Caillaud, Catherine; Sonnino, Sandro

2014-08-01

124

Therapeutic Potential of Intracerebroventricular Replacement of Modified Human ?-Hexosaminidase B for GM2 Gangliosidosis  

PubMed Central

To develop a novel enzyme replacement therapy for neurodegenerative Tay-Sachs disease (TSD) and Sandhoff disease (SD), which are caused by deficiency of ?-hexosaminidase (Hex) A, we designed a genetically engineered HEXB encoding the chimeric human ?-subunit containing partial amino acid sequence of the ?-subunit by structure-based homology modeling. We succeeded in producing the modified HexB by a Chinese hamster ovary (CHO) cell line stably expressing the chimeric HEXB, which can degrade artificial anionic substrates and GM2 ganglioside in vitro, and also retain the wild-type (WT) HexB-like thermostability in the presence of plasma. The modified HexB was efficiently incorporated via cation-independent mannose 6-phosphate receptor into fibroblasts derived from Tay-Sachs patients, and reduced the GM2 ganglioside accumulated in the cultured cells. Furthermore, intracerebroventricular administration of the modified HexB to Sandhoff mode mice restored the Hex activity in the brains, and reduced the GM2 ganglioside storage in the parenchyma. These results suggest that the intracerebroventricular enzyme replacement therapy involving the modified HexB should be more effective for Tay-Sachs and Sandhoff than that utilizing the HexA, especially as a low-antigenic enzyme replacement therapy for Tay-Sachs patients who have endogenous WT HexB. PMID:21487393

Matsuoka, Kazuhiko; Tamura, Tomomi; Tsuji, Daisuke; Dohzono, Yukie; Kitakaze, Keisuke; Ohno, Kazuki; Saito, Seiji; Sakuraba, Hitoshi; Itoh, Kohji

2011-01-01

125

Therapeutic potential of intracerebroventricular replacement of modified human ?-hexosaminidase B for GM2 gangliosidosis.  

PubMed

To develop a novel enzyme replacement therapy for neurodegenerative Tay-Sachs disease (TSD) and Sandhoff disease (SD), which are caused by deficiency of ?-hexosaminidase (Hex) A, we designed a genetically engineered HEXB encoding the chimeric human ?-subunit containing partial amino acid sequence of the ?-subunit by structure-based homology modeling. We succeeded in producing the modified HexB by a Chinese hamster ovary (CHO) cell line stably expressing the chimeric HEXB, which can degrade artificial anionic substrates and GM2 ganglioside in vitro, and also retain the wild-type (WT) HexB-like thermostability in the presence of plasma. The modified HexB was efficiently incorporated via cation-independent mannose 6-phosphate receptor into fibroblasts derived from Tay-Sachs patients, and reduced the GM2 ganglioside accumulated in the cultured cells. Furthermore, intracerebroventricular administration of the modified HexB to Sandhoff mode mice restored the Hex activity in the brains, and reduced the GM2 ganglioside storage in the parenchyma. These results suggest that the intracerebroventricular enzyme replacement therapy involving the modified HexB should be more effective for Tay-Sachs and Sandhoff than that utilizing the HexA, especially as a low-antigenic enzyme replacement therapy for Tay-Sachs patients who have endogenous WT HexB. PMID:21487393

Matsuoka, Kazuhiko; Tamura, Tomomi; Tsuji, Daisuke; Dohzono, Yukie; Kitakaze, Keisuke; Ohno, Kazuki; Saito, Seiji; Sakuraba, Hitoshi; Itoh, Kohji

2011-06-01

126

Electrokinetic and electrostatic properties of bilayers containing gangliosides GM1, GD1a, or GT1. Comparison with a nonlinear theory.  

PubMed Central

We formed vesicles from mixtures of egg phosphatidylcholine (PC) and the gangliosides GM1, GD1a, or GT1 to model the electrokinetic properties of biological membranes. The electrophoretic mobilities of the vesicles are similar in NaCl, CsCl, and TMACl solutions, suggesting that monovalent cations do not bind significantly to these gangliosides. If we assume the sialic acid groups on the gangliosides are located some distance from the surface of the vesicle and the sugar moieties exert hydrodynamic drag, we can describe the mobility data in 1, 10, and 100 mM monovalent salt solutions with a combination of the Navier-Stokes and nonlinear Poisson-Boltzmann equations. The values we assume for the thickness of the ganglioside head group and the location of the charge affect the theoretical predictions markedly, but the Stokes radius of each sugar and the location of the hydrodynamic shear plane do not. We obtain a reasonable fit to the mobility data by assuming that all ganglioside head groups project 2.5 nm from the bilayer and all fixed charges are in a plane 1 nm from the bilayer surface. We tested the latter assumption by estimating the surface potentials of PC/ganglioside bilayers using four techniques: we made 31P nuclear magnetic resonance, fluorescence, electron spin resonance, and conductance measurements. The results are qualitatively consistent with our assumption. PMID:3697476

McDaniel, R V; Sharp, K; Brooks, D; McLaughlin, A C; Winiski, A P; Cafiso, D; McLaughlin, S

1986-01-01

127

GM2 gangliosidosis B1 variant: biochemical and molecular characterization of hexosaminidase A.  

PubMed

The biochemical properties of hexosaminidase A (HexA) and the coding sequence of the alpha-subunit were examined in a patient of Syrian ancestry with the B1 form of Tay-Sachs disease (TSD). The biochemical characteristics of the variant HexA suggest that both active sites are affected by the mutation(s). Kinetic studies with the beta-subunit specific substrate, 4-methylumbelliferyl-beta-D-N-acetylglucosamine (MUG), revealed a significant difference between the Km values. of normal and variant HexA, while no difference was found when the sulfated substrate MUG-6-sulfate (MUGS), which is specific for the alpha-subunit active site, was used. The Vmax values for both substrates were significantly lower in extracts from B1 variant cells than in control extracts, implying a reduced enzyme level in the variant cells. A noncompetitive inhibitor of the reaction with MUGS, N-acetylglucosamine (NAG), induced a significant inhibition (30%) in the mutant cells only. When MUG was used as substrate, variant HexA was found to be more heat stable (T50 = 170 min) than normal HexA (T50 = 65 min). Furthermore, the mutant cell preparation differed from control in the relation between Hex thermosensitivity and protein concentration in the reaction. Two new mutations were identified in exon 5 of the HexA gene: a C496 to G transversion, which produced an Arg166 -->Gly alteration and a deletion of C498 which generated a shift in the reading frame. The patient was a heterozygote for both mutations even though her parents are first cousins. There is no evidence as yet which of these mutations accounts for the B1 phenotype. PMID:8581357

Peleg, L; Meltzer, F; Karpati, M; Goldman, B

1995-04-01

128

Histochemical detection of GM1 ganglioside using cholera toxin-B subunit. Evaluation of critical factors optimal for in situ detection with special emphasis to acetone pre-extraction.  

PubMed

A comparison of histochemical detection of GM1 ganglioside in cryostat sections using cholera toxin B-subunit after fixation with 4% formaldehyde and dry acetone gave tissue-dependent results. In the liver no pre-treatment showed detectable differences related to GM1 reaction products, while studies in the brain showed the superiority of acetone pre-extraction (followed by formaldehyde), which yielded sharper images compared with the diffuse, blurred staining pattern associated with formaldehyde. Therefore, the aim of our study was to define the optimal conditions for the GM1 detection using cholera toxin B-subunit. Ganglioside extractability with acetone, the ever neglected topic, was tested comparing anhydrous acetone with acetone containing admixture of water. TLC analysis of acetone extractable GM1 ganglioside from liver sections did not exceed 2% of the total GM1 ganglioside content using anhydrous acetone at -20 degrees C, and 4% at room temperature. The loss increased to 30.5% using 9:1 acetone/water. Similarly, photometric analysis of lipid sialic acid, extracted from dried liver homogenates with anhydrous acetone, showed the loss of gangliosides into acetone 3.0 +/- 0.3% only. The loss from dried brain homogenate was 9.5 +/- 1.1%. Thus, anhydrous conditions (dry tissue samples and anhydrous acetone) are crucial factors for optimal in situ ganglioside detection using acetone pre-treatment. This ensures effective physical fixation, especially in tissues rich in polar lipids (precipitation, prevention of in situ diffusion), and removal of cholesterol, which can act as a hydrophobic blocking barrier. PMID:20558344

Petr, T; Smíd, V; Smídová, J; H?lková, H; Jirkovská, M; Elleder, M; Muchová, L; Vitek, L; Smíd, F

2010-01-01

129

Real-Time PCR Genotyping Assay for GM2 Gangliosidosis Variant 0 in Toy Poodles and the Mutant Allele Frequency in Japan  

PubMed Central

ABSTRACT GM2 gangliosidosis variant 0 (Sandhoff disease, SD) is a fatal, progressive neurodegenerative lysosomal storage disease caused by mutations of the HEXB gene. In canine SD, a pathogenic mutation (c.283delG) of the canine HEXB gene has been identified in toy poodles. In the present study, a TaqMan probe-based real-time PCR genotyping assay was developed and evaluated for rapid and large-scale genotyping and screening for this mutation. Furthermore, a genotyping survey was carried out in a population of toy poodles in Japan to determine the current mutant allele frequency. The real-time PCR assay clearly showed all genotypes of canine SD. The assay was suitable for large-scale survey as well as diagnosis, because of its high throughput and rapidity. The genotyping survey demonstrated a carrier frequency of 0.2%, suggesting that the current mutant allele frequency is low in Japan. However, there may be population stratification in different places, because of the founder effect by some carriers. Therefore, this new assay will be useful for the prevention and control of SD in toy poodles. PMID:24161966

RAHMAN, Mohammad Mahbubur; YABUKI, Akira; KOHYAMA, Moeko; MITANI, Sawane; MIZUKAMI, Keijiro; UDDIN, Mohammad Mejbah; CHANG, Hye-Sook; KUSHIDA, Kazuya; KISHIMOTO, Miori; YAMABE, Remi; YAMATO, Osamu

2013-01-01

130

Effects of GM 1 -ganglioside and ?-sialyl cholesterol on amino acid uptake, protein synthesis, and Na + , K + ATPase activity in superior cervical and nodose ganglia excised from adult rats  

Microsoft Academic Search

We examined the effect of GM1-ganglioside in combination with cholera toxin B, and synthetic ?-sialyl cholesterol (?-SC) on neutral amino acid (tritiated\\u000a ?-aminoisobutyric acid, [3H]AIB) uptake, protein synthesis ([3H]leucine incorporation), and Na+, K+-ATPase activity in isolated superior cervical ganglia (SCG) and nodose ganglia (NG) from adult rats after aerobic incubation,\\u000a usually for 2 h at 37°C in vitro.\\u000a \\u000a Cholera toxin

Masato Ando; Yuhzo Nakashima; Yutaka Nagata

1990-01-01

131

The decreased susceptibility of Bcr/Abl targets to NK cell-mediated lysis in response to imatinib mesylate involves modulation of NKG2D ligands, GM1 expression, and synapse formation.  

PubMed

Chronic myeloid leukemia is a clonal multilineage myeloproliferative disease of stem cell origin characterized by the presence of the Bcr/Abl oncoprotein, a constitutively active tyrosine kinase. In previous studies, we have provided evidence that Bcr/Abl overexpression in leukemic cells increased their susceptibility to NK-mediated lysis by different mechanisms. In the present study, using UT-7/9 cells, a high level Bcr/Abl transfectant of UT-7 cells, we show that the treatment of Bcr/Abl target by imatinib mesylate (IM), a specific Abl tyrosine kinase inhibitor, hampers the formation of the NK/target immunological synapse. The main effect of IM involves an induction of surface GM1 ganglioside on Bcr/Abl transfectants that prevents the redistribution of MHC-related Ag molecules in lipid rafts upon interaction with NK cells. IM also affects cell surface glycosylation of targets, as assessed by binding of specific lectins resulting in the subsequent modulation of their binding to lectin type NK receptor, particularly NKG2D. In addition, we demonstrate that the tyrosine kinase activity repression results in a decrease of MHC-related Ags-A/B and UL-16-binding protein expression on Bcr/Abl transfectants UT-7/9. We show that NKG2D controls the NK-mediated lysis of UT-7/9 cells, and IM treatment inhibits this activating pathway. Taken together, our results show that the high expression of Bcr/Abl in leukemic cells controls the expression of NKG2D receptor ligands and membrane GM1 via a tyrosine kinase-dependent mechanism and that the modulation of these molecules by IM interferes with NK cell recognition and cytolysis of the transfectants. PMID:16393970

Cebo, Christelle; Da Rocha, Sylvie; Wittnebel, Sebastian; Turhan, Ali G; Abdelali, Jalil; Caillat-Zucman, Sophie; Bourhis, Jean Henri; Chouaib, Salem; Caignard, Anne

2006-01-15

132

Gangliosidosis with total hexosaminidase deficiency: Clinical, biochemical and ultrastructural studies and comparison with conventional cases of Tay-Sachs disease  

Microsoft Academic Search

Biochemical studies were performed on brain biopsies, and ultrastructural studies on brain and liver biopsies from three children presenting clinically the infantile form of Tay-Sachs disease. Gangliosides were markedly increased both in grey and white matter, and consisted mainly of fraction GM2. In one case (patient 1), the amount of N-acetylaminotrihexosyl-ceramide, the asialo-residue of ganglioside GM2, was much larger than

G. Fontaine; A. Résibois; M. Tondeur; G. Jonniaux; J. P. Farriaux; W. Voet; E. Maillard; H. Loeb

1973-01-01

133

Chronic GM2 gangliosidosis masquerading as atypical Friedreich ataxia: clinical, morphologic, and biochemical studies of nine cases.  

PubMed

A progressive spinocerebellar degenerative disorder was characterized in nine patients, aged 11 to 37 years, from four unrelated Ashkenazi Jewish families; affected individuals had markedly deficient beta-hexosaminidase A activity. Symptoms included early onset of cerebellar signs (tremor, incoordination, and dysarthia) and, with maturity, the development of upper and lower motor neuron disorders, marked dysarthia, and ataxia. Three older patients, aged 26, 32, and 37 years, had dementia or recurrent psychotic episodes. Membrane-bound lamellar cytoplasmic inclusions, consistent with lysosomal ganglioside accumulation, were observed in rectal ganglia. The activity of beta-hexosaminidase A was markedly deficient in all sources analyzed. Parents had activities consistent with heterozygosity, confirming autosomal-recessive transmission of the beta-hexosaminidase A-deficient gene and the adult variant disorder. Residual beta-hexosaminidase A activity, partially purified by anion-exchange chromatography from cultured skin fibroblasts of the affected individuals, was heat-labile and co-electrophoresed with normal beta-hexosaminidase A. These findings suggest that these patients were allelic for a new beta-hexosaminidase A mutation and may represent a genetic compound of this allele and the allele causing Tay-Sachs disease. PMID:6454083

Willner, J P; Grabowski, G A; Gordon, R E; Bender, A N; Desnick, R J

1981-07-01

134

W474C amino acid substitution affects early processing of the alpha-subunit of beta-hexosaminidase A and is associated with subacute G(M2) gangliosidosis.  

PubMed

Mutations in the HEXA gene, encoding the alpha-subunit of beta-hexosaminidase A (Hex A), that abolish Hex A enzyme activity cause Tay-Sachs disease (TSD), the fatal infantile form of G(M2) gangliosidosis, Type 1. Less severe, subacute (juvenile-onset) and chronic (adult-onset) variants are characterized by a broad spectrum of clinical manifestations and are associated with residual levels of Hex A enzyme activity. We identified a 1422 G-->C (amino acid W474C) substitution in the first position of exon 13 of HEXA of a non-Jewish proband who manifested a subacute variant of G(M2) gangliosidosis. On the second maternally inherited allele, we identified the common infantile disease-causing 4-bp insertion, +TATC 1278, in exon 11. Pulse-chase analysis using proband fibroblasts revealed that the W474C-containing alpha-subunit precursor was normally synthesized, but not phosphorylated or secreted, and the mature lysosomal alpha-subunit was not detected. When the W474C-containing alpha-subunit was transiently co-expressed with the beta-subunit to produce Hex A (alphabeta) in COS-7 cells, the mature alpha-subunit was present, but its level was much lower than that from normal alpha-subunit transfections, although higher than in those cells transfected with an alpha-subunit associated with infantile TSD. Furthermore, the precursor level of the W474C alpha-subunit was found to accumulate in comparison to the normal alpha-subunit precursor levels. We conclude that the 1422 G-->C mutation is the cause of Hex A enzyme deficiency in the proband. The resulting W474C substitution clearly interferes with alpha-subunit processing, but because the base substitution falls at the first position of exon 13, aberrant splicing may also contribute to Hex A deficiency in this proband. PMID:9603435

Petroulakis, E; Cao, Z; Clarke, J T; Mahuran, D J; Lee, G; Triggs-Raine, B

1998-01-01

135

The cherry-red spot in Tay-Sachs and other storage diseases.  

PubMed

The disappearance of the cherry-red spot in an otherwise typical patient with Tay-Sachs disease is described and illustrated. This clinical observation has rarely been made, but it is consistent with the pathological finding of loss of retinal ganglion cells. Disappearance of the cherry-red spot has also been observed in GM1 generalized gangliosidosis, the sialidoses known as the cherry-red spot-myoclonus syndrome and the Goldberg syndrome, and Niemann-Pick, type C disease. Thus the absence of a cherry-red spot in the neurologically impaired child or adult does not exclude these diagnoses. PMID:4004157

Kivlin, J D; Sanborn, G E; Myers, G G

1985-04-01

136

Altered ion channel formation by the Parkinson's-disease-linked E46K mutant of alpha-synuclein is corrected by GM3 but not by GM1 gangliosides.  

PubMed

Alpha-synuclein (alpha-syn) is an amyloidogenic protein that plays a key role in the pathogenesis of Parkinson's disease (PD). The ability of alpha-syn oligomers to form ionic channels is postulated as a channelopathy mechanism in human brain. Here we identified a ganglioside-binding domain in alpha-syn (fragment 34-50), which includes the mutation site 46 linked to a familial form of PD (E46K). We show that this fragment is structurally related to the common glycosphingolipid-binding domain (GBD) shared by various microbial and amyloid proteins, including Alzheimer's beta-amyloid peptide. alpha-Syn GBD interacts with several glycosphingolipids but has a marked preference for GM3, a minor brain ganglioside whose expression increases with aging. The alpha-syn mutant E46K has a stronger affinity for GM3 than the wild-type protein, and the interaction is inhibited by 3'-sialyllactose (the glycone part of GM3). Alanine substitutions of Lys34 and Tyr39 in synthetic GBD peptides resulted in limited interaction with GM3, demonstrating the critical role of these residues in GM3 recognition. When incubated with reconstituted phosphatidylcholine bilayers, the E46K protein formed channels that are five times less conductive than those formed by wild-type alpha-syn, exhibit a higher selectivity for cations, and present an asymmetrical response to voltage and nonstop single-channel activity. This E46K-associated channelopathy was no longer observed when GM3 was present in phosphatidylcholine bilayers. This corrective effect was highly specific for GM3, since it was not obtained with the major brain ganglioside GM1 but was still detected in bilayer membranes containing both GM3 and GM1. Moreover, synthetic GBD peptides prevented the interaction of alpha-syn proteins with GM3, thus abolishing the regulatory effects of GM3 on alpha-syn-mediated channel formation. Overall, these data show that GM3 can specifically regulate alpha-syn-induced channel formation and raise the intriguing possibility that this minor brain ganglioside could play a key protective role in the pathogenesis of PD. PMID:20114052

Di Pasquale, Eric; Fantini, Jacques; Chahinian, Henri; Maresca, Marc; Taïeb, Nadira; Yahi, Nouara

2010-03-19

137

Liquid chromatography/electrospray ionisation-tandem mass spectrometry quantification of GM2 gangliosides in human peripheral cells and plasma.  

PubMed

GM2 gangliosidosis is a group of inherited neurodegenerative disorders resulting primarily from the excessive accumulation of GM2 gangliosides (GM2) in neuronal cells. As biomarkers for categorising patients and monitoring the effectiveness of developing therapies are lacking for this group of disorders, we sought to develop methodology to quantify GM2 levels in more readily attainable patient samples such as plasma, leukocytes, and cultured skin fibroblasts. Following organic extraction, gangliosides were partitioned into the aqueous phase and isolated using C18 solid-phase extraction columns. Relative quantification of three species of GM2 was achieved using LC/ESI-MS/MS with d35GM1 18:1/18:0 as an internal standard. The assay was linear over the biological range, and all GM2 gangliosidosis patients were demarcated from controls by elevated GM2 in cultured skin fibroblast extracts. However, in leukocytes only some molecular species could be used for differentiation and in plasma only one was informative. A reduction in GM2 was easily detected in patient skin fibroblasts after a short treatment with media from normal cells enriched in secreted ?-hexosaminidase. This method may show promise for measuring the effectiveness of experimental therapies for GM2 gangliosidosis by allowing quantification of a reduction in the primary storage burden. PMID:24769373

Fuller, Maria; Duplock, Stephen; Hein, Leanne K; Rigat, Brigitte A; Mahuran, Don J

2014-08-01

138

Inheritance of Lysosomal Acid ? Galactosidase Activity and Gangliosides in Crosses of DBA\\/2J and Knockout Mice  

Microsoft Academic Search

GM1 gangliosidosis is a progressive neurodegenerative disease caused by deficiencies in lysosomal acid ß-galactosidase (ß-gal) and involves accumulation and storage of ganglioside GM1 and its asialo form (GA1) in brain and visceral tissues. Similar to the infantile\\/juvenile human disease forms, B6\\/129Sv ß-gal knockout (ko) mice express residual tissue ß-gal activity and significant elevations of brain GM1, GA1, and total gangliosides.

Eric C. Hauser; Julie L. Kasperzyk; Alessandra d'Azzo; Thomas N. Seyfried

2004-01-01

139

Patient \\  

Microsoft Academic Search

Contemporary medical decision making has been characterized as a struggle be- tween patients who are reportedly making more demands for medical interventions such as diagnostic tests and prescription drugs and physicians who are encouraged to partner with patients and satisfy them while simultaneously keeping medical costs down. Understanding this dynamic requires attention to the interactional strategies whereby patients indicate what

Virginia Teas Gill

2005-01-01

140

Clinical phenotype of patients with neuropathy associated with monoclonal gammopathy: a comparative study and a review of the literature.  

PubMed

The objective of this study was to investigate if the clinical and electrophysiological phenotype of patients with polyneuropathy associated with IgM monoclonal gammopathy (IgM-PNP) is related to the presence of antibodies against gangliosides or myelin-associated glycoprotein (MAG). We compared clinical and nerve conduction study (NCS) characteristics of 11 IgM-PNP patients with antibodies against asialo-GM1 or gangliosides (GM1, GD1a, GD1b, GM2 or GQ1b) to 11 consecutive IgM-PNP patients with anti-MAG neuropathy and to 9 IgM-PNP patients without antibodies against either MAG or gangliosides. Patients with anti-ganglioside antibodies could not be differentiated from those with anti-MAG antibodies based on clinical characteristics. However, within the group of anti-ganglioside antibody positive patients, antibodies against GD1b and GQ1b were associated with a purely sensory neuropathy (p = 0.002), while asymmetric weakness with symmetric sensory loss was associated with anti-asialo-GM1 antibodies. In conclusion, polyneuropathy associated with IgM monoclonal gammopathy and anti-ganglioside antibodies clinically resembles anti-MAG neuropathy. Pure sensory neuropathy and marked asymmetry may suggest the presence of anti-ganglioside rather than anti-MAG antibodies. PMID:24781837

Stork, Abraham C J; van der Pol, W-Ludo; Franssen, Hessel; Jacobs, Bart C; Notermans, Nicolette C

2014-07-01

141

Prenatal and postnatal studies of a late infantile GM2 gangliosidosis in a family of Syrian origin: a possible B1 variant.  

PubMed

We describe late infantile Tay-Sachs disease with high residual hexosaminidase A activity in two siblings of a Syrian Druze family. The patients' leukocytes had 26% of normal hexosaminidase A activity when tested with the conventional fluorogenic substrate 4-methyl-umbelliferyl-2-acetamido-2-deoxy-beta-D-glucopyranoside (4-MUG) and only about 10% when assayed with the sulfated substrate, 4-methyl-umbelliferal- beta-N-acetyl-glucosamine-6-sulfate (4-MUGS). According to the standard procedure of the heterozygote screening program (employing 4-MUG and heat inactivation), the parents were not diagnosed as an at-risk couple since the father was classified as a noncarrier. However, both parents' levels were clearly within the carrier range on the basis of 4-MUGS. The unique catalytic characteristics of the patients' enzyme forward the assumption that the affected sibs are B1 variants. The parents' enzymatic levels, together with their known consanguinity, might indicate that these patients are homozygotes for the rare mutation and not genetic compounds as has been documented for most of the infantile B1 variants. To the best of our knowledge this is the first reported case of B1 variant in a child of that extraction. PMID:8244659

Shukry, A; Goldman, B; Shihab, S; Peleg, L

1993-10-01

142

Lending a helping hand, screening chemical libraries for compounds that enhance beta-hexosaminidase A activity in GM2 gangliosidosis cells.  

PubMed

Enzyme enhancement therapy is an emerging therapeutic approach that has the potential to treat many genetic diseases. Candidate diseases are those associated with a mutant protein that has difficulty folding and/or assembling into active oligomers in the endoplasmic reticulum. Many lysosomal storage diseases are candidates for enzyme enhancement therapy and have the additional advantage of requiring only 5-10% of normal enzyme levels to reduce and/or prevent substrate accumulation. Our long experience in working with the beta-hexosaminidase (EC 3.2.1.52) isozymes system and its associated deficiencies (Tay-Sachs and Sandhoff disease) lead us to search for possible enzyme enhancement therapy-agents that could treat the chronic forms of these diseases which express 2-5% residual activity. Pharmacological chaperones are enzyme enhancement therapy-agents that are competitive inhibitors of the target enzyme. Each of the known beta-hexosaminidase inhibitors (low microm IC50) increased mutant enzyme levels to >or= 10% in chronic Tay-Sachs fibroblasts and also attenuated the thermo-denaturation of beta-hexosaminidase. To expand the repertoire of pharmacological chaperones to more 'drug-like' compounds, we screened the Maybridge library of 50,000 compounds using a real-time assay for noncarbohydrate-based beta-hexosaminidase inhibitors and identified several that functioned as pharmacological chaperones in patient cells. Two of these inhibitors had derivatives that had been tested in humans for other purposes. These observations lead us to screen the NINDS library of 1040 Food and Drug Administration approved compounds for pharmacological chaperones. Pyrimethamine, an antimalarial drug with well documented pharmacokinetics, was confirmed as a beta-hexosaminidase pharmacological chaperone and compared favorably with our best carbohydrate-based pharmacological chaperone in patient cells with various mutant genotypes. PMID:17894780

Tropak, Michael B; Mahuran, Don

2007-10-01

143

Cerebellar ataxia and polyneuropathy in a patient with IgM M-protein specific to the Gal(beta 1-3)GalNAc epitope.  

PubMed

A 79-year-old man with sensory dominant polyneuropathy, cerebellar ataxia, and palatal myoclonus had serum IgM M-protein that specifically bound to GM1, GD1b, and asialo-GM1. IgM with the same specificity was detected in his cerebrospinal fluid. Results of immunohistochemical studies showed specific binding of this monoclonal IgM to the cerebellar granular layer, dentate nucleus, inferior olive, and gray matter of the cerebrum and spinal cord. Monoclonal antibody GGR12, monospecific to GD1b, had an immunostaining distribution similar to that of the patient's IgM M-protein. The binding of M-protein may be associated with the development of cerebellar ataxia and palatal myoclonus in this patient. PMID:7531761

Hitoshi, S; Kusunoki, S; Chiba, A; Takatsu, R; Sunada, Y; Nukina, N; Tai, T; Kanazawa, I

1994-11-01

144

Macular Cherry-Red Spot Helps Diagnose Rare Storage Disorder in an Infant with Repeated Respiratory Tract Infections: Case Report.  

PubMed

Abstract A seven-month-old male child was brought in for an eye test for poor vision and nystagmus noticed from four months of age. The child had delayed milestones of development and multiple (six times) episodes of unexplained lower respiratory tract infection (from two months of age) treated by pediatricians at different centers without complete cure. Fundus examination showed bilateral cherry-red spots at the macula. There were diffusely distributed hyper-pigmented patches (Mongolian spots) on the back and extensor aspect of the extremities. The case was sent back to the pediatricians for a re-evaluation to rule out storage disorder. Lysosomal enzyme assay in the leucocytes showed a significantly reduced ?-galactosidase level (15.6?nmol/hr/mg protein in contrast to a normal range of 79.6 to 480.0). This confirmed the patient to be a case of lysosomal storage disease, the GM1 gangliosidosis (type I). PMID:24124800

Padhi, Tapas Ranjan; Pattnaik, Sibabrata; Kesarwani, Siddharth; Das, Taraprasad

2013-10-14

145

Three Novel Mutations in Iranian Patients with Tay-Sachs Disease  

PubMed Central

Background: Tay-Sachs disease (TSD), or GM2 gangliosidosis, is a lethal autosomal recessive neurodegenerative disorder, which is caused by a deficiency of beta-hexosaminidase A (HEXA), resulting in lysosomal accumulation of GM2 ganglioside. The aim of this study was to identify the TSD-causing mutations in an Iranian population. Methods: In this study, we examined 31 patients for TSD-causing mutations using PCR, followed by restriction enzyme digestion. Results: Molecular genetics analysis of DNA from 23 patients of TSD revealed mutations that has been previously reported, including four-base duplications c.1274_1277dupTATC in exon 11 and IVS2+1G>A, deletion TTAGGCAAGGGC in exon 10 as well as a few novel mutations, including C331G, which altered Gln>Glu in HEXB, A>G, T>C, and p.R510X in exon 14, which predicted a termination codon or nonsense mutation. Conclusion: In conclusion, with the discovery of these novel mutations, the genotypic spectrum of Iranian patients with TSD disease has been extended and could facilitate definition of disease-related mutations. PMID:24518553

Jamali, Solmaz; Eskandari, Nasim; Aryani, Omid; Salehpour, Shadab; Zaman, Talieh; Kamalidehghan, Behnam; Houshmand, Massoud

2014-01-01

146

Magnetic Resonance Findings of the Corpus Callosum in Canine and Feline Lysosomal Storage Diseases  

PubMed Central

Several reports have described magnetic resonance (MR) findings in canine and feline lysosomal storage diseases such as gangliosidoses and neuronal ceroid lipofuscinosis. Although most of those studies described the signal intensities of white matter in the cerebrum, findings of the corpus callosum were not described in detail. A retrospective study was conducted on MR findings of the corpus callosum as well as the rostral commissure and the fornix in 18 cases of canine and feline lysosomal storage diseases. This included 6 Shiba Inu dogs and 2 domestic shorthair cats with GM1 gangliosidosis; 2 domestic shorthair cats, 2 familial toy poodles, and a golden retriever with GM2 gangliosidosis; and 2 border collies and 3 chihuahuas with neuronal ceroid lipofuscinoses, to determine whether changes of the corpus callosum is an imaging indicator of those diseases. The corpus callosum and the rostral commissure were difficult to recognize in all cases of juvenile-onset gangliosidoses (GM1 gangliosidosis in Shiba Inu dogs and domestic shorthair cats and GM2 gangliosidosis in domestic shorthair cats) and GM2 gangliosidosis in toy poodles with late juvenile-onset. In contrast, the corpus callosum and the rostral commissure were confirmed in cases of GM2 gangliosidosis in a golden retriever and canine neuronal ceroid lipofuscinoses with late juvenile- to early adult-onset, but were extremely thin. Abnormal findings of the corpus callosum on midline sagittal images may be a useful imaging indicator for suspecting lysosomal storage diseases, especially hypoplasia (underdevelopment) of the corpus callosum in juvenile-onset gangliosidoses. PMID:24386203

Hasegawa, Daisuke; Tamura, Shinji; Nakamoto, Yuya; Matsuki, Naoaki; Takahashi, Kimimasa; Fujita, Michio; Uchida, Kazuyuki; Yamato, Osamu

2013-01-01

147

Comparison of the canine and human acid {beta}-galactosidase gene  

SciTech Connect

Several canine cDNA libraries were screened with human {beta}-galactosidase cDNA as probe. Seven positive clones were isolated and sequenced yielding a partial (2060 bp) canine {beta}-galactosidase cDNA with 86% identity to the human {beta}-galactosidase cDNA. Preliminary analysis of a canine genomic library indicated conservation of exon number and size. Analysis by Northern blotting disclosed a single mRNA of 2.4 kb in fibroblasts and liver from normal dogs and dogs affected with GM1 gangliosidosis. Although incomplete, these results indicate canine GM1 gangliosidosis is a suitable animal model of the human disease and should further efforts to devise a gene therapy strategy for its treatment. 20 refs., 2 figs., 1 tab.

Ahern-Rindell, A.J. [Weber State Univ., Ogden, UT (United States)] [Weber State Univ., Ogden, UT (United States); Kretz, K.A. [Recombinant BioCatalysis, Inc., La Jolla, CA (United States)] [Recombinant BioCatalysis, Inc., La Jolla, CA (United States); O`Brien, J.S. [Univ. of California at San Diego, La Jolla, CA (United States)] [Univ. of California at San Diego, La Jolla, CA (United States)

1996-05-17

148

Distribution of saposin proteins (sphingolipid activator proteins) in lysosomal storage and other diseases.  

PubMed Central

Saposins (A, B, C, and D) are small glycoproteins required for the hydrolysis of sphingolipids by specific lysosomal hydrolases. Concentrations of these saposins in brain, liver, and spleen from normal humans as well as patients with lysosomal storage disease were determined. A quantitative HPLC method was used for saposin A, C, and D and a stimulation assay was used for saposin B. In normal tissues, saposin D was the most abundant of the four saposins. Massive accumulations of saposins, especially saposin A (about 80-fold increase over normal), were found in brain of patients with Tay-Sachs disease or infantile Sandhoff disease. In spleen of adult patients with Gaucher disease, saposin A and D accumulations (60- and 17-fold, respectively, over normal) were higher than that of saposin C (about 16-fold over normal). Similar massive accumulations of saposins A and D were found in liver of patients with fucosidosis (about 70- and 20-fold, respectively, over normal). Saposin D was the primary saposin stored in the liver of a patient with Niemann-Pick disease (about 30-fold over normal). Moderate increases of saposins B and D were found in a patient with GM1 gangliosidosis. Normal or near normal levels of all saposins were found in patients with Krabbe disease, metachromatic leukodystrophy, Fabry disease, adrenoleukodystrophy, I-cell disease, mucopolysaccharidosis types 2 and 3B, or Jansky-Bielschowsky disease. The implications of the storage of saposins in these diseases are discussed. PMID:2110365

Morimoto, S; Yamamoto, Y; O'Brien, J S; Kishimoto, Y

1990-01-01

149

Glycosphingolipid storage leads to the enhanced degradation of the B cell receptor in Sandhoff disease mice  

Microsoft Academic Search

Glycosphingolipid storage diseases are a group of inherited metabolic diseases in which glycosphingolipids accumulate due\\u000a to their impaired lysosomal breakdown. Splenic B cells isolated from NPC1, Sandhoff, GM1-gangliosidosis and Fabry disease\\u000a mouse models showed large (20- to 30-fold) increases in disease specific glycosphingolipids and up to a 4-fold increase in\\u000a cholesterol. The magnitude of glycosphingolipid storage was in the order

Danielle te Vruchte; Aruna Jeans; Frances M. Platt; Daniel John Sillence

2010-01-01

150

Anti-neuronal antibodies in patients with HCV-related mixed cryoglobulinemia.  

PubMed

Mixed cryoglobulinemia (MC) is an immunological disorder characterized by immune-complex-mediated systemic vasculitis involving small vessels, which may present with renal, cutaneous, rheumatologic, and/or neurological manifestations. Until recently, the possible appearance of anti-neuronal autoantibodies in peripheral neuropathy occurring in the context of hepatitis C virus (HCV)-associated IgMk/IgG MC has not been extensively addressed. Therefore, a sample of these patients were evaluated by means of immuno-enzyme methods of anti-neuronal autoantibody detection. A significant increase in plasma titers of both anti-GM1 ganglioside and anti-sulfatide was observed. Abnormal titers were associated with evidence of active neuropathy as assessed by electrophysiologic studies. While peripheral neuropathy was traditionally thought to result from axonal ischemic damage caused by deposits of cryoprecipitable immune complexes in the vasa nervorum, a significant association between anti-GM1 and anti-sulfatide antibodies and involvement of the peripheral nervous system was observed in HCV-associated mixed IgMk/IgG cryoglobulinemia. Anti-neuronal reactivity could be a direct trigger of neurologic injury in this disorder. PMID:18703170

Alpa, M; Ferrero, B; Cavallo, R; Naretto, C; Menegatti, E; Di Simone, D; Napoli, F; La Grotta, R; Rossi, D; Baldovino, S; Sena, L M; Roccatello, D

2008-10-01

151

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

SciTech Connect

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

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

1989-04-01

152

Gangliosidoses.  

PubMed

The gangliosidoses comprise a family of lysosomal storage diseases characterized by the accumulation of complex glycosphingolipids in the nervous system and other tissues, secondary to the deficient activity of lysosomal hydrolases or their associated activator proteins. GM1 and GM2 gangliosidosis are associated with deficiency of ?-galactosidase and ?-hexosaminidase respectively. All gangliosidoses are characterized by progressive neurodegeneration, the severity of which is proportional to the residual enzyme activity. The GM1 gangliosidoses are characterized by dysostosis, organomegaly and coarsening in their most severe forms, whereas children with classic infantile GM2 gangliosidosis (Tay-Sachs disease) are usually spared systemic involvement, except in the case of the Sandhoff variant, in which organomegaly may occur. Cherry-red macular spots occur in the early onset forms of the gangliosidoses, but are less frequently seen in the less severe, later onset phenotypes. Macrocephaly, an exaggerated startle response, cognitive decline, seizures, ataxia, and progressive muscular atrophy may occur in different forms of gangliosidosis. The diagnosis is made by assay of enzyme activity, and can be confirmed by mutation analysis. Carrier screening for Tay-Sachs disease has been remarkably successful in reducing the incidence of this disease in the at-risk Ashkenazi population. There are no proven disease-modifying therapies for the gangliosidoses. PMID:23622392

Patterson, Marc C

2013-01-01

153

Fast urinary screening of oligosaccharidoses by MALDI-TOF/TOF mass spectrometry  

PubMed Central

Background Oligosaccharidoses, which belong to the lysosomal storage diseases, are inherited metabolic disorders due to the absence or the loss of function of one of the enzymes involved in the catabolic pathway of glycoproteins and indirectly of glycosphingolipids. This enzymatic deficiency typically results in the abnormal accumulation of uncompletely degraded oligosaccharides in the urine. Since the clinical features of many of these disorders are not specific for a single enzyme deficiency, unambiguous screening is critical to limit the number of costly enzyme assays which otherwise must be performed. Methods Here we provide evidence for the advantages of using a MALDI-TOF/TOF (matrix-assisted laser desorption ionization time-of-flight) mass spectrometric (MS) method for screening oligosaccharidoses. Urine samples from previously diagnosed patients or from unaffected subjects were randomly divided into a training set and a blind testing set. Samples were directly analyzed without prior treatment. Results The characteristic MS and MS/MS molecular profiles obtained allowed us to identify fucosidosis, aspartylglucosaminuria, GM1 gangliosidosis, Sandhoff disease, ?-mannosidosis, sialidosis and mucolipidoses type II and III. Conclusions This method, which is easily run in less than 30 minutes, is performed in a single step, and is sensitive and specific. Invaluable for clinical chemistry purposes this MALDI-TOF/TOF mass spectrometry procedure is semi-automatizable and suitable for the urinary screening of oligosacharidoses. PMID:24502792

2014-01-01

154

Scientific literature on monosialoganglioside in the Science Citation Index-Expanded  

PubMed Central

BACKGROUND: The monosialoganglioside (GM1) is a popular topic of research but the bibliometric analysis of GM1 over the decades in Science Citation Index-Expanded (SCI-E) remains poorly understood. OBJECTIVE: To identify the global research and to improve the understanding of research trends in the GM1 field from 1942 to 2011. DESIGN: A bibliometric study. DATA RETRIEVAL: We performed a bibliometric analysis based on the SCI-E published by the Institute of Scientific Information. INCLUSIVE CRITERIA: Articles closely related to GM1 were included. Exclusive criteria: (1) Articles related to gangliosidosis, disialo-ganglioside, trisialo-ganglioside or ganglioside GQIb. (2) Document types such as meeting abstracts, reviews, proceedings papers, notes, and letters. MAIN OUTCOME MEASURES: (1) Type of publication output; (2) number of author outputs; (3) distribution of output in subject categories; (4) publication distribution of countries; (5) distribution of output in journals, and (6) distribution of citations in each decade. RESULTS: During 1942 to 2011, there were 10 126 papers on GM1 that were added to the SCI. Articles (8 004) were the most frequently used document type comprising 79.0%, followed by meeting abstracts, reviews and proceedings papers. Research on GM1 could be found in the SCI from 1942, it was developed in the 1970s, greatly increased in the 1980s, and reached a peak in the 1990s, and it was slightly decreased in 2000. The distribution of subject categories showed that GM1 research covered both clinical and basic science research. The USA, Japan, and Germany were the three most productive countries, and the publication numbers in the USA were highest in all decades. The Journal of Biological Chemistry, Journal of Neurochemistry and Biochemistry were core subject journals in GM1 studies in each decade. CONCLUSION: This study highlights the topics in GM1 research that are being published around the world.

Xu, Yanli; Li, Miaojing; Liu, Zhijun; Liu, Ruichun; Zhang, Jianzhong

2012-01-01

155

Normalizing glycosphingolipids restores function in CD4+ T cells from lupus patients.  

PubMed

Patients with the autoimmune rheumatic disease systemic lupus erythematosus (SLE) have multiple defects in lymphocyte signaling and function that contribute to disease pathogenesis. Such defects could be attributed to alterations in metabolic processes, including abnormal control of lipid biosynthesis pathways. Here, we reveal that CD4+ T cells from SLE patients displayed an altered profile of lipid raft-associated glycosphingolipids (GSLs) compared with that of healthy controls. In particular, lactosylceramide, globotriaosylceramide (Gb3), and monosialotetrahexosylganglioside (GM1) levels were markedly increased. Elevated GSLs in SLE patients were associated with increased expression of liver X receptor ? (LXR?), a nuclear receptor that controls cellular lipid metabolism and trafficking and influences acquired immune responses. Stimulation of CD4+ T cells isolated from healthy donors with synthetic and endogenous LXR agonists promoted GSL expression, which was blocked by an LXR antagonist. Increased GSL expression in CD4+ T cells was associated with intracellular accumulation and accelerated trafficking of GSL, reminiscent of cells from patients with glycolipid storage diseases. Inhibition of GSL biosynthesis in vitro with a clinically approved inhibitor (N-butyldeoxynojirimycin) normalized GSL metabolism, corrected CD4+ T cell signaling and functional defects, and decreased anti-dsDNA antibody production by autologous B cells in SLE patients. Our data demonstrate that lipid metabolism defects contribute to SLE pathogenesis and suggest that targeting GSL biosynthesis restores T cell function in SLE. PMID:24463447

McDonald, Georgia; Deepak, Shantal; Miguel, Laura; Hall, Cleo J; Isenberg, David A; Magee, Anthony I; Butters, Terry; Jury, Elizabeth C

2014-02-01

156

Normalizing glycosphingolipids restores function in CD4+ T cells from lupus patients  

PubMed Central

Patients with the autoimmune rheumatic disease systemic lupus erythematosus (SLE) have multiple defects in lymphocyte signaling and function that contribute to disease pathogenesis. Such defects could be attributed to alterations in metabolic processes, including abnormal control of lipid biosynthesis pathways. Here, we reveal that CD4+ T cells from SLE patients displayed an altered profile of lipid raft–associated glycosphingolipids (GSLs) compared with that of healthy controls. In particular, lactosylceramide, globotriaosylceramide (Gb3), and monosialotetrahexosylganglioside (GM1) levels were markedly increased. Elevated GSLs in SLE patients were associated with increased expression of liver X receptor ? (LXR?), a nuclear receptor that controls cellular lipid metabolism and trafficking and influences acquired immune responses. Stimulation of CD4+ T cells isolated from healthy donors with synthetic and endogenous LXR agonists promoted GSL expression, which was blocked by an LXR antagonist. Increased GSL expression in CD4+ T cells was associated with intracellular accumulation and accelerated trafficking of GSL, reminiscent of cells from patients with glycolipid storage diseases. Inhibition of GSL biosynthesis in vitro with a clinically approved inhibitor (N-butyldeoxynojirimycin) normalized GSL metabolism, corrected CD4+ T cell signaling and functional defects, and decreased anti-dsDNA antibody production by autologous B cells in SLE patients. Our data demonstrate that lipid metabolism defects contribute to SLE pathogenesis and suggest that targeting GSL biosynthesis restores T cell function in SLE. PMID:24463447

McDonald, Georgia; Deepak, Shantal; Miguel, Laura; Hall, Cleo J.; Isenberg, David A.; Magee, Anthony I.; Butters, Terry; Jury, Elizabeth C.

2014-01-01

157

Energy Forecast Model Based on Combination of GM(1,1) and Neural Network  

Microsoft Academic Search

Energy consumption forecast is an essential component in making energy plan. In the light of the complexity and nonlinearity of energy consumption system, the gray forecast model and neural network model are respectively established by using the energy consumption historical data of certain province. Then their advantages and disadvantages are analyzed. Lastly, the method of optimal combination is applied in

Ren-yuan Liu; Jue Zhang; Qiang Huang; Bao-dong Lei

2009-01-01

158

Glycosidases: inborn errors of glycosphingolipid catabolism.  

PubMed

Glycosphingolipids (GSLs) are information-rich glycoconjugates that occur in nature mainly as constituents of biomembranes. Each GSL contains a complex carbohydrate chain linked to a ceramide moiety that anchors the molecule to biomembranes. In higher animals, catabolism of GSLs takes place in lysosomes where sugar chains in GSLs are hydrolyzed by exo-glycosidases to cleave a sugar residue from the non-reducing end of a sugar chain. Inborn errors of GSL-catabolism, collectively called sphingolipidoses or GSL-storage diseases, are caused by the deficiency of exo-glycosidases responsible for the degradation of the specific sugar residues at the non-reducing termini in GSLs. This chapter briefly discusses glycone, anomeric, linkage, and aglycone specificities of exo-glycosidases and some of the historical landmarks on their associations with the chemical pathology of the five best known sphingolipidoses: GM1 gangliosidosis, GM2 gangliosidosis (Tay-Sachs disease), Fabry disease, Gaucher disease, and Krabbe disease. PMID:25151392

Ashida, Hisashi; Li, Yu-Teh

2014-01-01

159

Incidence Rates and Deaths of Tuberculosis in HIV-Negative Patients in the United States and Germany as Analyzed by New Predictive Model for Infection  

PubMed Central

Incidence and mortality due to tuberculosis (TB) have been decreasing worldwide. Given that TB is a cosmopolitan disease, proper surveillance and evaluation are critical for controlling dissemination. Herein, mathematical modeling was performed in order to: 1) demonstrate a correlation between the incidence of TB in HIV-free patients in the US and Germany, and their corresponding mortality rates; 2) show the utility of the newly developed D-R algorithm for analyzing and predicting the incidence of TB in both countries; and 3) inform us on population death rates due to TB in HIV-negative patients. Using data published by the World Health Organization between 1990 and 2009, the relationship between incidence and mortality that could not be ascribed to HIV infection was evaluated. Using linear, quadratic and cubic curves, we found that a cubic function provided the best fit with the data in both the US (Y?=?2.3588+2.2459X+61.1639X2?60.104X3) and Germany (Y?=?1.9271+9.4967X+18.3824X2?10.350X3) where the correlation coefficient (R) between incidence and mortality was 0.995 and 0.993, respectively. Second, we demonstrated that fitted curves using the D-R model were equal to or better than those generated using the GM(1,1) algorithm as exemplified in the relative values for Sum of Squares of Error, Relative Standard Error, Mean Absolute Deviation, Average Relative Error, and Mean Absolute Percentage Error. Finally, future trends using both the D-R and the classic GM(1,1) models predicted a continued decline in infection and mortality rates of TB in HIV-negative patients rates extending to 2015 assuming no changes to diagnosis or treatment regimens are enacted. PMID:23077479

Suo, Siqingaowa; Bu, Ri-e; Zarlenga, Dante S.; Ren, Xiaofeng

2012-01-01

160

Selective screening for lysosomal storage diseases with dried blood spots collected on filter paper in 4,700 high-risk colombian subjects.  

PubMed

Lysosomal storage disorders (LSDs) are a very heterogeneous group of hereditary disorders. The diagnostic process usually involves complex sampling, processing, testing, and validation procedures, performed by specialized laboratories only, which causes great limitations in reaching a diagnosis for patients affected by these diseases.There are few studies about LSDs in Colombia. The diagnostic limitations often make medical practitioners disregard the possibility of these disorders while diagnosing their patients. The current study documents the results of a 7-year screening in high-risk patients, aimed to detect LSDs using dried blood spots (DBS) collected on filter paper, with a micromethodology that facilitates diagnosis even with a large number of samples.The activities of ?-galactosidase A, ? glucosidase, ?-L-iduronidase, arylsulfatase B, ?-galactosidase, ?-glucosidase, total hexosaminidase, iduronate sulfatase, and chitotriosidase were analyzed in high-risk patients for lysosomal disease. The catalytic activity was evaluated with fluorometric micromethods using artificial substrates marked with 4-methylumbelliferone.The reference values for a control population were established for the enzymes listed above, and 242 patients were found to have an enzyme deficiency, guiding to the following diagnoses: Fabry disease (n = 31), Pompe disease (n = 16), Hurler Syndrome (n = 15), Maroteaux-Lamy Syndrome (n = 34), GM1 Gangliosidosis (n = 10), Morquio B (n = 1), Gaucher disease (n = 101), Sandhoff disease (n = 1), Mucolipidosis (n = 2), and Hunter Syndrome (n = 31). In conclusion, this protocol provides a comprehensive diagnostic approach which could be carried out in Colombia and made it available to medical services spread around the country, enabling the identification of a large number of patients affected by LSDs, which could potentially benefit from the therapeutic tools already available for many of these diseases. PMID:23609959

Uribe, Alfredo; Giugliani, Roberto

2013-01-01

161

Patient Rights  

MedlinePLUS

As a patient, you have certain rights. Some are guaranteed by federal law, such as the right to get a copy ... them private. Many states have additional laws protecting patients, and healthcare facilities often have a patient bill ...

162

Patient satisfaction.  

PubMed

Patient satisfaction is an important and commonly used indicator for measuring the quality in health care. Patient satisfaction affects clinical outcomes, patient retention, and medical malpractice claims. It affects the timely, efficient, and patient-centered delivery of quality health care. Patient satisfaction is thus a proxy but a very effective indicator to measure the success of doctors and hospitals. This article discusses as to how to ensure patient satisfaction in dermatological practice. PMID:21430827

Prakash, Bhanu

2010-09-01

163

Patient Satisfaction  

PubMed Central

Patient satisfaction is an important and commonly used indicator for measuring the quality in health care. Patient satisfaction affects clinical outcomes, patient retention, and medical malpractice claims. It affects the timely, efficient, and patient-centered delivery of quality health care. Patient satisfaction is thus a proxy but a very effective indicator to measure the success of doctors and hospitals. This article discusses as to how to ensure patient satisfaction in dermatological practice. PMID:21430827

Prakash, Bhanu

2010-01-01

164

Patient Advocacy  

Cancer.gov

CPTAC recognizes the important role that patients, patient advocates, and other members outside of the traditional science community play in advancing cancer research, and is actively involved in dialogue with such communities.  To this end the consortium

165

BEN Patient  

USGS Multimedia Gallery

Balkan endemic nephropathy (BEN) patient from a BEN village in Romania. The photo was taken at a dialysis clinic in Romania where the patient traveled every 2 to 3 days to receive dialysis, the principal treatment option for people with BEN. This patient died from complications of BEN within a year ...

166

Expression of lysosomal enzymes in human mutant fibroblast-chick erythrocyte heterokaryons.  

PubMed

The generation of enzymes located in lysosomes, in cytosol or in endoplasmatic reticulum/Golgi complex is studied in heterokaryons in which chick erythrocyte nuclei are reactivated. The lysosomal enzymes, alpha-glucosidase (alpha-glu) and beta-galactosidase (beta-gal), are synthesized in heterokaryons obtained after fusion of chick erythrocytes with human fibroblasts of patients with Pompe's disease (alpha-glu-deficient) and GM1-gangliosidosis (beta-gal-deficient), respectively. The enzymes appear to be of chick origin and their activities can be detected at first around 4 days after fusion, i.e., at a time when the nucleoli in the erythrocyte nuclei have been reactivated. Maximal activities are reached around 15 days after fusion. No generation of the lysosomal enzyme beta-hexosaminidase is detected in the heterokaryons up to 23 days after fusion of chick erythrocyte with either beta-hexosaminidase A- and B-deficient fibroblasts (Sandhoff's disease) or beta-hexosaminidase A-deficient fibroblasts (Tay-Sachs disease). Similarly no expression of the cytosol enzyme glucose-6-phosphate dehydrogenase (G6PD) is fond up to 30 days after fusion, when chick erythrocytes are fused with fibroblasts from two different G6PD-deficient cell strains (residual activities of 4 and 20% respectively). Indirectly we examined N-acetyl-glucosamine-1-phosphate transferase activity, an enzyme located in the endoplasmic reticulum/Golgi region. This enzyme is needed for the phosphorylation of the lysosomal hydrolases and absence of its activity is the cause of the multiple lysosomal enzyme deficiencies in patients with I-cell disease. The retention of both, chick and human beta-galactosidase in the experiments in which I-cell fibroblasts were fused with chick erythrocytes indicates a reactivation of the gene coding for this phosphorylating enzyme. It also implies that this step in the processing of human lysosomal enzymes is not species-specific. PMID:6291965

Van der Veer, E; Barneveld, R A; Reuser, A J

1982-11-01

167

Patient Corner  

Cancer.gov

Biospecimens contain an extraordinary amount of biological information, written in the language of cells, genes and proteins. Each biospecimen is also defined by a clinical context - the age, gender, race, diet, and various aspects of the environment the patient has been exposed to during his life. The personal and clinical information comes from interviews at the time the specimen is donated, from medical records patients consent to provide, and from clinical trials that patients volunteer to join.

168

Frustrating patients  

Microsoft Academic Search

Objective:To identify differences between patients viewed as frustrating by their physicians and those considered typical and satisfying.\\u000a \\u000a Design:This cross-sectional observational study focused on psychologically distressed high users of medical services. Frustrating\\u000a patients were compared with typical and satisfying patients, using data from patient questionnaires, physician assessments,\\u000a structured psychiatric interviews, and computerized utilization records.\\u000a \\u000a \\u000a \\u000a Setting:Group Health Cooperative of Puget Sound, a

Elizabeth H. B. Lin; Wayne Katon; Michael Von Korff; Terry Bush; Patricia Lipscomb; Joan Russo; Ed Wagner

1991-01-01

169

Naturally occurring G M2 gangliosidosis in two Muntjak deer with pathological and biochemical features of human classical Tay-Sachs disease (type B G M2 gangliosidosis)  

Microsoft Academic Search

Two juvenile sibling male Muntjak deer (Muntiacus muntjak) with histories of depression, ataxia, circling and visual deficits were studied. Cerebrospinal fluid analyses revealed vacuolated\\u000a macrophages that contained long parallel needle-like intracytoplasmic inclusions. Light microscopically, nerve cell bodies\\u000a throughout the brain, ganglion cells within the retina and neurons in the myenteric plexuses were variably swollen and had\\u000a pale granular to finely

J. Fox; Y.-T. Li; G. Dawson; A. Alleman; J. Johnsrude; J. Schumacher; B. Homer

1999-01-01

170

Glucosylceramide modulates endolysosomal pH in Gaucher disease.  

PubMed

GlcCer accumulation causes Gaucher disease where GlcCer breakdown is inhibited due to a hereditary deficiency in glucocerebrosidase. Glycolipids are endocytosed and targeted to the Golgi apparatus in normal cells but in Gaucher disease they are mistargeted to lysosomes. To better understand the role of GlcCer in endocytic sorting RAW macrophages were treated with Conduritol B-epoxide to inhibit GlcCer breakdown. Lipid analysis found increases in GlcCer led to accumulation of both triacylglycerol and cholesterol consistent with increased lysosomal pH. Ratio imaging of macrophages using both acridine orange and lysosensor yellow/blue to measure endolysosomal pH revealed increases in Conduritol B-epoxide treated RAW macrophages and Gaucher patient lymphoblasts. Increased endolysosomal pH was restricted to Gaucher lymphoblasts as no significant increases in pH were seen in Fabry, Krabbe, Tay-Sachs and GM1-gangliosidosis lymphoblasts. Substrate reduction therapy utilises inhibitors of GlcCer synthase to reduce storage in Gaucher disease. The addition of inhibitors of GlcCer synthesis to RAW macrophages also led to increases in cholesterol and triacylglycerol and an endolysosomal pH increase of up to 1 pH unit. GlcCer modulation appears specific since glucosylsphingosine but not galactosylsphingosine reversed the effects of GlcCer depletion. Although no acute effects on glycolipid trafficking were observed using bafilomycin A the results are consistent with a multistep model whereby increases in pH lead to altered trafficking via cholesterol accumulation. GlcCer modulates endolysosomal pH in lymphocytes suggesting an important role in normal lysosomes which may be disrupted in Gaucher disease. PMID:23628459

Sillence, Dan J

2013-06-01

171

PATIENT NAVIGATION  

PubMed Central

Background First implemented in 1990, patient navigation interventions are emerging as an approach to reduce cancer disparities. However, there is lack of consensus about how patient navigation is defined, what patient navigators do, and what their qualifications should be. Little is known about the efficacy and cost effectiveness of patient navigation. Methods We conducted a qualitative synthesis of published literature on cancer patient navigation. Using the keywords “navigator” or “navigation” and “cancer,” we identified 45 articles from Pubmed and reference searches that were published or in press through October 2007. 16 provided data on efficacy of navigation in improving timeliness and receipt of cancer screening, diagnostic follow-up care, and treatment. Patient navigation services are defined and differentiated from other outreach services. Results Overall there is evidence for some degree of efficacy for patient navigation in increasing participation in cancer screening and adherence to diagnostic follow-up care following an abnormality, with increases in screening ranging from 10.8% to 17.1% and increases in adherence to diagnostic follow-up care ranging from 21% to 29.2%, when compared to control patients. There is less evidence regarding efficacy of patient navigation in reducing either late stage cancer diagnosis or delays in initiation of cancer treatment or improving outcomes during cancer survivorship. There were methodological limitations in most studies, such as lack of control groups, small sample sizes, and contamination with other interventions. Conclusions Although cancer-related patient navigation interventions are being increasingly adopted across the U.S. and Canada, further research is necessary to evaluate their efficacy and cost-effectiveness in improving cancer care. PMID:18780320

Wells, Kristen J.; Battaglia, Tracy A.; Dudley, Donald J.; Garcia, Roland; Greene, Amanda; Calhoun, Elizabeth; Mandelblatt, Jeanne S.; Paskett, Electra D.; Raich, Peter C.

2008-01-01

172

Patient passport.  

PubMed

This article outlines the development, testing and evaluation of a patient passport designed specifically for people with severe asthma, who often prefer to self-manage rather than attend emergency services, and thereby put their lives at risk. PMID:25369963

2014-11-01

173

Endogenous immune response to gangliosides in patients with confined prostate cancer.  

PubMed

Our study investigated whether endogenous IgM antibodies to gangliosides occur in patients with early stages of prostate cancer (CaP) patients, after defining ganglioside profiles of CaP cell lines. Immune and resorcinol staining detected the presence of gangliosides GM3, GM2, GD3, GD2 and GD1a but not GM1a, GD1b or GT1b in the extracts of normal prostatic epithelial cells (PrEC) and neoplastic androgen-insensitive (PC-3, DU145) and -sensitive (LNCaP-FGC and LNCaP-FGC-10) CaP cells. Using a sensitive ELISA, developed and validated in our laboratory, the titers of IgM against 8 gangliosides from sera of patients with benign prostatic hyperplasia (BPH) (n = 11), organ-confined (T1/T2, n = 36) and unconfined (T3/T4, n = 27) CaP and age-matched healthy men (n = 11) were determined double-blinded. Using ANOVA and Fisher's least significant difference (LSD) methods, the log-titers among different groups were compared. CaP patients differed from healthy and BPH patients in increased titers against GD1a and decreased titers against GD3. Titers of antibodies to other gangliosides exhibited no difference between CaP patients and others. The specific augmentation of anti-GD1a IgM in patients with organ-confined CaP (stage T1/T2) but not in patients with unconfined CaP (stage T3/T4) or BPH or in healthy controls is striking. This finding together with identification of GD1a as a major ganglioside in CaP cell lines and with the accruing studies on the immunosuppressive nature of GD1a indicates that augmentation of anti-GD1a IgM in confined CaP may signify an early endogenous immune response to eliminate a "danger signal" from tumor microenvironment and circulation. PMID:15818621

Ravindranath, Mepur H; Muthugounder, Sakunthala; Presser, Naftali; Ye, Xing; Brosman, Stanley; Morton, Donald L

2005-09-01

174

Patient Corner  

Cancer.gov

Biospecimens are materials taken from the human body, such as tissue, blood, plasma, and urine that can be used for cancer diagnosis and analysis. When patients have a biopsy, surgery, or other procedure, often a small amount of the specimen removed can be stored and used for later research. Once these samples have been properly processed and stored they are known as human biospecimens.

175

Patient Corner  

Cancer.gov

As a patient scheduled for a biopsy or surgery, you may be asked before the procedure if you would consider donating a biospecimen for research. You will receive a brochure describing how the process works, as well as a consent form to review.

176

Patient Monitoring  

NASA Technical Reports Server (NTRS)

In photo above, the electrocardiogram of a hospitalized patient is being transmitted by telemetry. Widely employed in space operations, telemetry is a process wherein instrument data is converted to electrical signals and sent to a receiver where the signals are reconverted to usable information. In this instance, heart readings are picked up by the electrode attached to the patient's body and delivered by wire to the small box shown, which is a telemetry transmitter. The signals are relayed wirelessly to the console in the background, which converts them to EKG data. The data is displayed visually and recorded on a printout; at the same time, it is transmitted to a central control station (upper photo) where a nurse can monitor the condition of several patients simultaneously. The Patient Monitoring System was developed by SCI Systems, Inc., Huntsville, Alabama, in conjunction with Abbott Medical Electronics, Houston, Texas. In developing the system, SCI drew upon its extensive experience as a NASA contractor. The company applied telemetry technology developed for the Saturn launch vehicle and the Apollo spacecraft; instrumentation technology developed for heart, blood pressure and sleep monitoring of astronauts aboard NASA's Skylab long duration space station; and communications technology developed for the Space Shuttle.

1978-01-01

177

Patient Zero”:  

PubMed Central

Summary This article contextualizes the production and reception of And the Band Played On, Randy Shilts’s popular history of the initial recognition of the American AIDS epidemic. Published over twenty-five years ago, the book and its most notorious character, “Patient Zero,” are in particular need of a critical historical treatment. The article presents a more balanced consideration—a “patient’s view”—of Gaétan Dugas’s experience of the early years of AIDS. I oppose the assertion that Dugas, the so-called Patient Zero, ignored incontrovertible information about the condition and was intent on spreading his infection. Instead I argue that scientific ideas in 1982 and 1983 about AIDS and the transmissibility of a causative agent were later portrayed to be more self-evident than they were at the time. The article also traces how Shilts’s highly selective—and highly readable—characterization of Dugas rapidly became embedded in discussions about the need to criminalize the reckless transmission of HIV. PMID:24769806

McKay, Richard A.

2014-01-01

178

State of the Art: Why do the lungs of patients with cystic fibrosis become infected and why can't they clear the infection?  

PubMed Central

Cystic Fibrosis (CF) lung disease, which is characterized by airway obstruction, chronic bacterial infection, and an excessive inflammatory response, is responsible for most of the morbidity and mortality. Early in life, CF patients become infected with a limited spectrum of bacteria, especially P. aeruginosa. New data now indicate that decreased depth of periciliary fluid and abnormal hydration of mucus, which impede mucociliary clearance, contribute to initial infection. Diminished production of the antibacterial molecule nitric oxide, increased bacterial binding sites (e.g., asialo GM-1) on CF airway epithelial cells, and adaptations made by the bacteria to the airway microenvironment, including the production of virulence factors and the ability to organize into a biofilm, contribute to susceptibility to initial bacterial infection. Once the patient is infected, an overzealous inflammatory response in the CF lung likely contributes to the host's inability to eradicate infection. In response to increased IL-8 and leukotriene B4 production, neutrophils infiltrate the lung where they release mediators, such as elastase, that further inhibit host defenses, cripple opsonophagocytosis, impair mucociliary clearance, and damage airway wall architecture. The combination of these events favors the persistence of bacteria in the airway. Until a cure is discovered, further investigations into therapies that relieve obstruction, control infection, and attenuate inflammation offer the best hope of limiting damage to host tissues and prolonging survival. PMID:14511398

Chmiel, James F; Davis, Pamela B

2003-01-01

179

Patient Education on Pain  

MedlinePLUS

... Education Annual Meeting Safe Prescribing Resources Clinical Pearls Patient Center Home > Patient Center > Patient Education > Patient Education ... to People with Pain Press Room Position Statements Patient Education on Pain AAPM Past President, Perry G. ...

180

Lipid Storage Diseases  

MedlinePLUS

... the enzyme beta-hexosaminidase. The GM2 disorders include: Tay-Sachs disease (also known as GM2 gangliosidosis-variant B). Tay- ... rarer form of the disorder, called late-onset Tay-Sachs disease, occurs in patients in their twenties and early ...

181

Patient Corner  

Cancer.gov

Biospecimens are biological materials from people (such as tissue, blood, plasma, and urine) that can be used for diagnosis and basic research. When cancer patients undergo procedures such as a blood draw, biopsy or surgery in which a specimen is removed for diagnostic or therapeutic purposes, it is often possible for a small amount of residual specimen to be stored and later used for research.

182

Gene Transfer Corrects Acute GM2 Gangliosidosis—Potential Therapeutic Contribution of Perivascular Enzyme Flow  

PubMed Central

The GM2 gangliosidoses are fatal lysosomal storage diseases principally affecting the brain. Absence of ?-hexosaminidase A and B activities in the Sandhoff mouse causes neurological dysfunction and recapitulates the acute Tay–Sachs (TSD) and Sandhoff diseases (SD) in infants. Intracranial coinjection of recombinant adeno-associated viral vectors (rAAV), serotype 2/1, expressing human ?-hexosaminidase ? (HEXA) and ? (HEXB) subunits into 1-month-old Sandhoff mice gave unprecedented survival to 2 years and prevented disease throughout the brain and spinal cord. Classical manifestations of disease, including spasticity—as opposed to tremor-ataxia—were resolved by localized gene transfer to the striatum or cerebellum, respectively. Abundant biosynthesis of ?-hexosaminidase isozymes and their global distribution via axonal, perivascular, and cerebrospinal fluid (CSF) spaces, as well as diffusion, account for the sustained phenotypic rescue—long-term protein expression by transduced brain parenchyma, choroid plexus epithelium, and dorsal root ganglia neurons supplies the corrective enzyme. Prolonged survival permitted expression of cryptic disease in organs not accessed by intracranial vector delivery. We contend that infusion of rAAV into CSF space and intraparenchymal administration by convection-enhanced delivery at a few strategic sites will optimally treat neurodegeneration in many diseases affecting the nervous system. PMID:22453766

Cachón-González, M Begoña; Wang, Susan Z; McNair, Rosamund; Bradley, Josephine; Lunn, David; Ziegler, Robin; Cheng, Seng H; Cox, Timothy M

2012-01-01

183

Therapeutic Potential of Intracerebroventricular Replacement of Modified Human ?-Hexosaminidase B for GM2 Gangliosidosis  

Microsoft Academic Search

To develop a novel enzyme replacement therapy for neurodegenerative Tay-Sachs disease (TSD) and Sandhoff disease (SD), which are caused by deficiency of ?-hexosaminidase (Hex) A, we designed a genetically engineered HEXB encoding the chimeric human ?-subunit containing partial amino acid sequence of the ?-subunit by structure-based homology modeling. We succeeded in producing the modified HexB by a Chinese hamster ovary

Kazuhiko Matsuoka; Tomomi Tamura; Daisuke Tsuji; Yukie Dohzono; Keisuke Kitakaze; Kazuki Ohno; Seiji Saito; Hitoshi Sakuraba; Kohji Itoh

2011-01-01

184

Gene transfer corrects acute GM2 gangliosidosis--potential therapeutic contribution of perivascular enzyme flow.  

PubMed

The GM2 gangliosidoses are fatal lysosomal storage diseases principally affecting the brain. Absence of ?-hexosaminidase A and B activities in the Sandhoff mouse causes neurological dysfunction and recapitulates the acute Tay-Sachs (TSD) and Sandhoff diseases (SD) in infants. Intracranial coinjection of recombinant adeno-associated viral vectors (rAAV), serotype 2/1, expressing human ?-hexosaminidase ? (HEXA) and ? (HEXB) subunits into 1-month-old Sandhoff mice gave unprecedented survival to 2 years and prevented disease throughout the brain and spinal cord. Classical manifestations of disease, including spasticity-as opposed to tremor-ataxia-were resolved by localized gene transfer to the striatum or cerebellum, respectively. Abundant biosynthesis of ?-hexosaminidase isozymes and their global distribution via axonal, perivascular, and cerebrospinal fluid (CSF) spaces, as well as diffusion, account for the sustained phenotypic rescue-long-term protein expression by transduced brain parenchyma, choroid plexus epithelium, and dorsal root ganglia neurons supplies the corrective enzyme. Prolonged survival permitted expression of cryptic disease in organs not accessed by intracranial vector delivery. We contend that infusion of rAAV into CSF space and intraparenchymal administration by convection-enhanced delivery at a few strategic sites will optimally treat neurodegeneration in many diseases affecting the nervous system. PMID:22453766

Cachón-González, M Begoña; Wang, Susan Z; McNair, Rosamund; Bradley, Josephine; Lunn, David; Ziegler, Robin; Cheng, Seng H; Cox, Timothy M

2012-08-01

185

Communicating with patients  

MedlinePLUS

... Ask your patients about their outlooks, attitudes, and motivations. Learn the patient's perspective. Talk to the patient ... beliefs. This will help you understand the patient's motivation and let you plan the best ways to ...

186

Carrier Rates of Four Single-Gene Disorders in Croatian Bayash Roma  

PubMed Central

To assess how specific population history, different migration routes, isolation, and endogamy practices contributed to the distribution of several rare diseases found in specific Roma groups, we conducted a population-based research study of rare disease mutations in Croatian Vlax Roma. We tested a total of 427 subjects from Baranja and Me?imurje for the presence of four mutations causing hereditary motor and sensory neuropathy type Lom (HMSNL), GM1 gangliosidosis (GM1), congenital cataracts, facial dysmorphism and neuropathy (CCFDN), and limb girdle muscle dystrophy type 2C (LGMD2C), using the RFLP-PCR method to estimate carrier frequencies. We identified a total of four individuals heterozygous for the mutation causing HMSNL in the Baranja population, with a carrier rate amounting to 1.5%. Carriers for other three mutations causing GM1, CCFDN, and LGMD2C were not found in our sample. The carrier rate for the HMSNL mutation in Baranja is lower than in other Vlax Roma groups. In addition, distinct differences in carrier rates between the Croatian Vlax groups point to different genetic history, despite their belonging to the same Roma migration category and subgroup. The difference in carrier rates is either the result of admixture or the reflection of a greater extent of genetic drift since recent founding, maintained by a high degree of endogamy. PMID:24180318

Bareši?, Ana

2014-01-01

187

[Patient advice].  

PubMed

In wound care, knowing what to do is as important as knowing what not to do. The first step is to evaluate the severity of the lesion and to know whether it is necessary to attend a health center or not. If the wound is simple, the recommended course of action is cleansing with serum or water after washing one's hands, followed by wound disinfection with the most appropriate antiseptic. Antiseptics not should be used for wound cleansing (physiological serum or tap water should be used) or for wound healing with granulation tissue. Equally, antiseptics should not be used in the ear or near the eyes; if there is accidental application, the eye should be washed in abundant water. Povidone iodine should not be used in pregnant women, nor should iodine preparations be used in neonates, in patients with thyroid alterations or in those allergic to iodine. Currently, merbromine/mercurochrome is not used because of its mercury content. Before an antiseptic is applied, all inorganic residues (foreign bodies) and dead tissue should be removed; detritus, slough, purulent exudate, scabs… This will aid healing and the action of antiseptics, since they become inactive in the presence of organic material. PMID:24998084

Lucio-Villegas Menéndez, M Eulalia; González, Laura López; Gutiérrez Pérez, M Isabel; Lluch, Natalia Aresté; Morató Agustí, M Luisa; Cachafeiro, Santiago Pérez

2014-05-01

188

Infusion of autologous bone marrow mononuclear cells leads to transient reduction in proteinuria in treatment refractory patients with Idiopathic membranous nephropathy  

PubMed Central

Background The current treatment options for idiopathic membranous nephropathy (IMN) carry significant toxicity. In this prospective, observational pilot study, we used single time infusion of bone marrow derived autologous mononuclear cells (MNCs) in adult patients with treatment refractory IMN. Methods Twelve patients of biopsy proven IMN who had failed a cyclical 6-month regimen of steroid and cyclophosphamide were enrolled in the study. Bone-marrow was harvested from the iliac crest and underwent processing to isolate MNCs. Cells were counted and subjected to viability testing before being infused through a peripheral vein on the same day. After the infusion, subjects were followed up monthly for the next six months. Supportive treatment including angiotensin antagonists and statins was continued throughout the study period. Result The proteinuria, serum albumin and creatinine values at entry were 2.97?±?0.6 gm/1.73 m2/d, 2.27?±?1.1 gm/l and 0.9?±?0.8 mg/dl respectively. There was a reduction in proteinuria (p?50% reduction in proteinuria. However, the response was ill sustained. At 6 months, only 2 patients had >50% reduction. Serum creatinine remained stable throughout the study period. No infusion related side effects were noted. Conclusion Autologous mononuclear cell infusion leads to transitory reduction in proteinuria and improvement in serum albumin in treatment refractory IMN. This effect, however, is transient. Whether this can be overcome by repeated infusion of cultured mesenchymal cells needs to be investigated. PMID:24289828

2013-01-01

189

JAMA Patient Page: Delirium  

MedlinePLUS

... article about diagnosing delirium. This Patient Page is based on one previously published in the ... find this and previous JAMA Patient Pages, go to the Patient Page link on JAMA ’s Web site at www.jama.com. ...

190

Counseling the Coronary Patient  

ERIC Educational Resources Information Center

The article discusses counseling sessions designed to a) help the coronary patient adjust to cardiovascular disease, b) diminish patient anxieties and fears, and c) educate the patient and family members on controlling risk factors to deter another coronary attack. (JS)

Semmler, Caryl; Semmler, Maynard

1974-01-01

191

Neuroaxonal dystrophy in neuronal storage disorders: evidence for major GABAergic neuron involvement.  

PubMed

The formation of focal granular enlargements within axons (axonal spheroids or "torpedoes"; neuroaxonal dystrophy) is a well known phenomenon occurring in a variety of neurological diseases. The relative susceptibility of different types of neurons to this kind of axonal pathology, however, is largely unknown. An immunocytochemical study directed at localizing glutamic acid decarboxylase (GAD), the synthetic enzyme for the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), in various CNS regions in feline models of lysosomal storage disorders has revealed vast numbers of axonal spheroids containing this enzyme. In some storage diseases (GM1 and GM2 gangliosidosis), GAD-immunoreactive spheroids were a common occurrence in many brain regions, whereas in other disorders these structures were more limited in distribution (alpha-mannosidosis), or were absent (mucopolysaccharidosis type I). Axonal spheroids unreactive for GAD were encountered in large numbers in subcortical white matter in GM2 gangliosidosis, but were infrequently observed in the other diseases. The incidence and distribution of GAD-immunoreactive spheroids in the various diseases under study were found to correlate closely with the type and degree of neurological deficits exhibited by affected animals. This study indicates that the neuroaxonal dystrophy occurring in some types of storage disorders commonly involves axons of GABAergic neurons and suggests that a resulting defect in neurotransmission in inhibitory circuits may be an important factor underlying brain dysfunction in this family of diseases. PMID:1919594

Walkley, S U; Baker, H J; Rattazzi, M C; Haskins, M E; Wu, J Y

1991-07-01

192

Successful mobilization of Ph-negative blood stem cells with intensive chemotherapy + G-CSF in patients with chronic myelogenous leukemia in first chronic phase.  

PubMed

The aim of the study was to investigate the feasibility of mobilizing Philadelphia chromosome negative (Ph-) blood stem cells (BSC) with intensive chemotherapy and lenograstim (G-CSF) in patients with CML in first chronic phase (CP1). During 1994-1999 12 centers included 37 patients <56 years. All patients received 6 months' IFN, stopping at median 36 (1-290) days prior to the mobilization chemotherapy. All received one cycle of daunorubicin 50 mg/m2 and 1 hour infusion on days 1-3, and cytarabine (ara-C) 200 mg/m2 24 hours' i.v. infusion on days 1-7 (DA) followed by G-CSF 526 microg s.c. once daily from day 8 after the start of chemotherapy. Leukaphereses were initiated when the number of CD 34+ cells was >5/microl blood. Patients mobilizing poorly could receive a 4-day cycle of chemotherapy with mitoxantrone 12 mg/m2/day and 1 hour i.v infusion, etoposide 100 mg/m2/day and 1 hour i.v. infusion and ara-C 1 g/m2/twice a day with 2 hours' i.v infusion (MEA) or a second DA, followed by G-CSF 526 microg s.c once daily from day 8 after the start of chemotherapy. Twenty-seven patients received one cycle of chemotherapy and G-CSF, whereas 10 were mobilized twice. Twenty-three patients (62%) were successfully (MNC >3.5 x 10(8)/kg, CFU-GM >1.0 x 10(4)/kg, CD34+ cells >2.0 x 10(6)/kg and no Ph+ cells in the apheresis product) [n = 16] or partially successfully (as defined above but 1-34% Ph+ cells in the apheresis product) [n = 7] mobilized. There was no mortality during the mobilization procedure. Twenty-one/23 patients subsequently underwent auto-SCT. The time with PMN <0.5 x 10(9)/l was 10 (range 7-49) and with platelets <20 x 10(9)/l was also 10 (2-173) days. There was no transplant related mortality. The estimated 5-year overall survival after auto-SCT was 68% (95% CI 47 - 90%), with a median follow-up time of 5.2 years.We conclude that in a significant proportion of patients with CML in CP 1, intensive chemotherapy combined with G-CSF mobilizes Ph- BSC sufficient for use in auto-SCT. PMID:17064986

Olsson-Strömberg, Ulla; Höglund, Martin; Björkholm, Magnus; Braide, Inger; Carlson, Karin; Gahrton, Gösta; Grimfors, Gunnar; Hast, Robert; Lerner, Rickard; Linder, Olle; Ljungman, Per; Löfvenberg, Eva; Malm, Claes; Nilsson, Per-Gunnar; Paul, Christer; Rödjer, Stig; Stenke, Leif; Tidefeldt, Ulf; Turesson, Ingemar; Uden, Ann-Marie; Wahlin, Anders; Vilen, Lars; Winqvist, Ingemar; Zettervall, Olle; Oberg, Gunnar; Simonsson, Bengt

2006-09-01

193

Repositioning the Patient:  

PubMed Central

Summary This article explores how and why the patient came to be repositioned as a political actor within British health care during the 1960s and 1970s. Focusing on the role played by patient organizations, it is suggested that the repositioning of the patient needs to be seen in the light of growing demands for greater patient autonomy and the application of consumerist principles to health. Examining the activities of two patient groups—the National Association for the Welfare of Children in Hospital (NAWCH) and the Patients Association (PA)—indicates that while such groups undoubtedly placed more emphasis on individual autonomy, collective concerns did not entirely fall away. The voices of patients, as well as the patient, continued to matter within British health care. PMID:23811711

Mold, Alex

2013-01-01

194

National Patient Safety Foundation  

MedlinePLUS

... Store Home Donate Help Creating a world where patients and those who care for them are free ... Joint Commission Journal Focus Archive Stand Up for Patient Safety Welcome Stand Up Members Stand Up e- ...

195

Working with Patients: Diagnosis  

MedlinePLUS

... Testing Information Health Care Professionals Materials Working with Patients Diagnosis Asbestos-related conditions can be difficult to ... the toxicological characteristics and health effects of asbestos. Patient Materials Living with Asbestos-Related Illness [ HTML ] Topics ...

196

Patient Awards and Scholarships  

MedlinePLUS

... and friends to get connected! Patient Awards and Scholarships 2015-2016 Scholarship and Award Information The Kidney & Urology Foundation of ... program. Kidney & Urology Foundation of America Vincent Stefano Scholarship Award This award is for college-bound patients ( ...

197

[Patient-ventilator interaction].  

PubMed

Mechanically ventilated patients interact with ventilator functions at different levels such as triggering of the ventilator, pressurization and cycling from inspiration to expiration. Patient ventilator asynchrony in any one of these phase results in fighting with ventilator, increase in work of breathing and respiratory muscle fatigue. Patient ventilator dyssynchrony occurs when gas delivery from the ventilator does not match with the neural output of the respiratory center. The clinical findings of patient-ventilator asynchrony are; use of accessory respiratory muscle, tachypnea, tachycardia, active expiration, diaphoresis and observation of asynchrony between patient respiratory effort and the ventilator waveforms. Among the patients with dynamic hyperinflation such as chronic obstructive pulmonary disease the most frequent causes of patient-ventilator asynchrony are trigger and expiratory asynchronies. In acute respiratory distress syndrome patient-ventilator asynchrony may develop due to problems in triggering or asynchrony in flow and inspiration-expiration cycle. Patient-ventilator interaction during noninvasive mechanical ventilation may be affected by the type of masks used, ventilator types, ventilation modes and parameters, humidification and sedation. Among the different patient groups it is important to know causes and solutions of patient-ventilator asynchrony problems. By this way patient will adapt ventilator and then dyspnea, ineffective respiratory effort and work of breathing may decrease subsequently. PMID:20037864

Gürsel, Gül; Aydo?du, Müge

2009-01-01

198

Modelling patient states in intensive care patients  

E-print Network

Extensive bedside monitoring in hospital Intensive Care Units (ICU) has resulted in a deluge of information on patient physiology. Consequently, clinical decision makers have to reason with data that is simultaneously large ...

Kshetri, Kanak Bikram

2011-01-01

199

[Patient safety in Sweden].  

PubMed

This article describes the patient safety work in Sweden and the cooperation between the Nordic countries in the area of patient safety. It depicts the national infrastructure, methods and partners in patient safety work as well as the development in key areas. Since 2000, the interest in patient safety and quality issues has significantly increased. A national study (2009) showed that more than 100,000 patients (8.6?%) experienced preventable harm in hospitals. Since 2007, all Swedish counties and regions work on the "National commitment for increased patient safety" to systematically minimize adverse events in the healthcare system. Also, a national strategy for patient safety has been proposed based on a new law regulating the responsibility for patient safety (2011) and a zero vision in terms of preventable harm and adverse events. The Nordic collaboration in this field currently focuses on the development of indicators and quality measurement with respect to nosocomial infections, harm in inpatient somatic care, patient safety culture, hospital mortality and polypharmacy in the elderly. The Nordic collaboration is driven by the development, exchange and documentation of experiences and evidence on patient safety indicators. The work presented in this article is only a part of the Swedish and the Nordic efforts related to patient safety and provides an interesting insight into how this work can be carried out. PMID:25430735

Rutberg, H; Eckhardt, M; Biermann, O

2015-01-01

200

Patient-centered Care.  

PubMed

Patient-centered care focuses on the patient and the individual's particular health care needs. The goal of patient-centered health care is to empower patients to become active participants in their care. This requires that physicians, radiologic technologists and other health care providers develop good communication skills and address patient needs effectively. Patient-centered care also requires that the health care provider become a patient advocate and strive to provide care that not only is effective but also safe. For radiologic technologists, patient-centered care encompasses principles such as the as low as reasonably achievable (ALARA) concept and contrast media safety. Patient-centered care is associated with a higher rate of patient satisfaction, adherence to suggested lifestyle changes and prescribed treatment, better outcomes and more cost-effective care. This article is a Directed Reading. Your access to Directed Reading quizzes for continuing education credit is determined by your area of interest. For access to other quizzes, go to www.asrt.org/store. According to one theory, most patients judge the quality of their healthcare much like they rate an airplane flight. They assume that the airplane is technically viable and is being piloted by competent people. Criteria for judging a particular airline are personal and include aspects like comfort, friendly service and on-time schedules. Similarly, patients judge the standard of their healthcare on nontechnical aspects, such as a healthcare practitioner's communication and "soft skills." Most are unable to evaluate a practitioner's level of technical skill or training, so the qualities they can assess become of the utmost importance in satisfying patients and providing patient-centered care.(1). PMID:19901351

Reynolds, April

2009-01-01

201

Overproduction of the CFTR R Domain Leads to Increased Levels of AsialoGM1 and Increased Pseudomonas aeruginosa Binding by Epithelial Cells  

Microsoft Academic Search

Mutations in cystic fibrosis transmembrane conductance regulator (CFTR), particularly the common D F508 mutation, have been associated with alterations in glycolipid sialylation and the availability of re- ceptors for Pseudomonas aeruginosa binding. The surface properties of 9HTEo 2 tracheal epithelial cell lines transfected with plasmids that overproduce the regulatory (R) domain of CFTR (pCEP-R) and lack cyclic adenosine monophosphate-stimulated Cl

Ruth Bryan; Dianne Kube; Aura Perez; Pamela Davis; Alice Prince

202

A Study of the Strategic Alliance for EMS Industry: The Application of a Hybrid DEA and GM (1,?1) Approach.  

PubMed

Choosing a partner is a critical factor for success in international strategic alliances, although criteria for partner selection vary between developed and transitional markets. This study aims to develop effective methods to assist enterprise to measure the firms' operation efficiency, find out the candidate priority under several different inputs and outputs, and forecast the values of those variables in the future. The methodologies are constructed by the concepts of Data Envelopment Analysis (DEA) and grey model (GM). Realistic data in four consecutive years (2009-2012) a total of 20 companies of the Electronic Manufacturing Service (EMS) industry that went public are completely collected. This paper tries to help target company-DMU1-to find the right alliance partners. By our proposed approach, the results show the priority in the recent years. The research study is hopefully of interest to managers who are in manufacturing industry in general and EMS enterprises in particular. PMID:25821859

Wang, Chia Nan; Nguyen, Nhu Ty; Tran, Thanh Tuyen; Huong, Bui Bich

2015-01-01

203

A Study of the Strategic Alliance for EMS Industry: The Application of a Hybrid DEA and GM (1,?1) Approach  

PubMed Central

Choosing a partner is a critical factor for success in international strategic alliances, although criteria for partner selection vary between developed and transitional markets. This study aims to develop effective methods to assist enterprise to measure the firms' operation efficiency, find out the candidate priority under several different inputs and outputs, and forecast the values of those variables in the future. The methodologies are constructed by the concepts of Data Envelopment Analysis (DEA) and grey model (GM). Realistic data in four consecutive years (2009–2012) a total of 20 companies of the Electronic Manufacturing Service (EMS) industry that went public are completely collected. This paper tries to help target company—DMU1—to find the right alliance partners. By our proposed approach, the results show the priority in the recent years. The research study is hopefully of interest to managers who are in manufacturing industry in general and EMS enterprises in particular.

Wang, Chia Nan; Tran, Thanh Tuyen; Huong, Bui Bich

2015-01-01

204

Enhanced analgesic potency and reduced tolerance of morphine in 129\\/SvEv mice: evidence for a deficiency in GM1 ganglioside-regulated excitatory opioid receptor functions  

Microsoft Academic Search

A recent study reported that chronic morphine treatment of the 129\\/SvEv strain of mice did not result in the usual development of tolerance observed in most other mouse strains. The authors' analyses suggested that the anomalous lack of tolerance in 129\\/SvEv mice might be due to a defect in NMDA receptor functions. However, our previous studies suggested that cellular signs

Stanley M. Crain; Ke-Fei Shen

2000-01-01

205

A model to evaluate the consequences of GM and non-GM1 segregation scenarios on GM crop placement in the landscape and2  

E-print Network

(genetically modified) if more than10 0.9% of one of its ingredients originates from GM material. During).45 In this paper, we consider the consequences of the introduction of Bt maize (resistant to corn46 stalk borer

Boyer, Edmond

206

Why measure patient satisfaction?  

PubMed

A practice that consistently and continuously measures patient perceptions will be more efficient and effective in its daily operations. With pay-for-performance requirements on the horizon and consumer rating sites already publicizing impressions from physician encounters, a practice needs to know how it is performing through the eyes of the patients. Azalea Orthopedics has used patient feedback to coach its physicians on better patient communication. The Orthopaedic Institute has used patient satisfaction results to reduce wait times and measure the return on investment from its marketing efforts. Patient survey results that are put to work can enhance the efficiency and effectiveness of practice operations as well as position the practice for increased profitability. PMID:21506460

Riskind, Patty; Fossey, Leslie; Brill, Kari

2011-01-01

207

[Vertigo: patient management tactics].  

PubMed

To avoid serious causes of dizziness and establishing preliminary diagnosis is usually enough sighting history taking and physical examination of the patient. Great importance is self-presenting patients with complaints of dizziness. In recent years, for treatment of various types vestybulopatiy, but also for the prevention of attacks, successfully used betahistyn hydrochloride, which improves the quality of care and well-being of the patient. PMID:23350121

Vasyl'chuk, I S; Kozlova, O O; Trinus, K F; Holovchenko, Iu I; Slobodin, T M

2012-01-01

208

Lipocalin-type prostaglandin D synthase is up-regulated in oligodendrocytes in lysosomal storage diseases and binds gangliosides.  

PubMed

Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is a dually functional protein, acting both as a PGD2-synthesizing enzyme and as an extracellular transporter of various lipophilic small molecules. L-PGDS is expressed in oligodendrocytes (OLs) in the central nervous system and is up-regulated in OLs of the twitcher mouse, a model of globoid cell leukodystrophy (Krabbe's disease). We investigated whether up-regulation of L-PGDS is either unique to Krabbe's disease or is a more generalized phenomenon in lysosomal storage disorders (LSDs), using LSD mouse models of Tay-Sachs disease, Sandhoff disease, GM1 gangliosidosis and Niemann-Pick type C1 disease. Quantitative RT-PCR revealed that L-PGDS mRNA was up-regulated in the brains of all these mouse models. In addition, strong L-PGDS immunoreactivity was observed in OLs, but not in either astrocytes or microglia in these models. Thus, up-regulation of L-PGDS appears to be a common response of OLs in LSDs. Moreover, surface plasmon resonance analyses revealed that L-PGDS binds GM1 and GM2 gangliosides, accumulated in neurons in the course of LSD, with high affinities (KD = 65 and 210 nm, respectively). This suggests that L-PGDS may play a role in scavenging harmful lipophilic substrates in LSD. PMID:16515539

Mohri, Ikuko; Taniike, Masako; Okazaki, Issei; Kagitani-Shimono, Kuriko; Aritake, Kosuke; Kanekiyo, Takahisa; Yagi, Takashi; Takikita, Shoichi; Kim, Hyung-Suk; Urade, Yoshihiro; Suzuki, Kinuko

2006-05-01

209

The Prevalence of Nine Genetic Disorders in a Dog Population from Belgium, the Netherlands and Germany  

PubMed Central

The objective of this study was to screen a dog population from Belgium, the Netherlands and Germany for the presence of mutant alleles associated with hip dysplasia (HD), degenerative myelopathy (DM), exercise-induced collapse (EIC), neuronal ceroid lipofuscinosis 4A (NCL), centronuclear myopathy (HMLR), mucopolysaccharidosis VII (MPS VII), myotonia congenita (MG), gangliosidosis (GM1) and muscular dystrophy (Duchenne type) (GRMD). Blood samples (K3EDTA) were collected for genotyping with Kompetitive Allele Specific PCR (n?=?476). Allele and genotype frequencies were calculated in those breeds with at least 12 samples (n?=?8). Hardy-Weinberg equilibrium was tested. Genetic variation was identified for 4 out of 9 disorders: mutant alleles were found in 49, 15, 3 and 2 breeds for HD, DM, EIC and NCL respectively. Additionally, mutant alleles were identified in crossbreeds for both HD and EIC. For HD, DM, EIC and NCL mutant alleles were newly discovered in 43, 13, 2 and 1 breed(s), respectively. In 9, 2 and 1 breed(s) for DM, EIC and NCL respectively, the mutant allele was detected, but the respective disorder has not been reported in those breeds. For 5 disorders (HMLR, MPS VII, MG, GM1, GRMD), the mutant allele could not be identified in our population. For the other 4 disorders (HD, DM, EIC, NCL), prevalence of associated mutant alleles seems strongly breed dependent. Surprisingly, mutant alleles were found in many breeds where the disorder has not been reported to date. PMID:24069350

Broeckx, Bart J. G.; Coopman, Frank; Verhoeven, Geert E. C.; Van Haeringen, Wim; van de Goor, Leanne; Bosmans, Tim; Gielen, Ingrid; Saunders, Jimmy H.; Soetaert, Sandra S. A.; Van Bree, Henri; Van Neste, Christophe; Van Nieuwerburgh, Filip; Van Ryssen, Bernadette; Verelst, Elien; Van Steendam, Katleen; Deforce, Dieter

2013-01-01

210

Identification of Sandhoff disease in a Thai family: clinical and biochemical characterization.  

PubMed

Sandhoff disease is a GM2 gangliosidosis that is rare in Thailand. The authors report a Thai family with two children known to have infantile form of Sandhoff disease. The index case exhibited mitral valve prolapse with mitral regurgitation as an early sign, which is a rare presentation in Sandhoff disease. Thereafter the patient had developmental regression, startle reaction, and cherry red spots. The diagnosis was confirmed by biochemical analysis. PMID:20873083

Sakpichaisakul, Kullasate; Taeranawich, Pairat; Nitiapinyasakul, Achara; Sirisopikun, Todsaporn

2010-09-01

211

Neuro-ophthalmology of late-onset Tay-Sachs disease (LOTS)  

Microsoft Academic Search

Background: Late-onset Tay-Sachs disease (LOTS) is an adult-onset, autosomal recessive, progressive variant of GM2 gangliosidosis, characterized by involvement of the cerebellum and anterior horn cells. Objective: To determine the range of visual and ocular motor abnormalities in LOTS, as a prelude to evaluating the effectiveness of novel therapies. Methods: Fourteen patients with biochemically confirmed LOTS (8 men; age range 24

J. C. Rucker; B. E. Shapiro; Y. H. Han; A. N. Kumar; S. Garbutt; E. L. Keller; R. J. Leigh

2004-01-01

212

Apoptotic Cell Death in Mouse Models of GM2 Gangliosidosis and Observations on Human Tay-Sachs and Sandhoff Diseases  

Microsoft Academic Search

Tay-Sachs and Sandhoff diseases are autosomal recessive neurodegenerative diseases resulting from the inability to catabolize GM2 ganglioside by ?-hexos- aminidase A (Hex A) due to mutations of the ? subunit (Tay-Sachs disease) or ? subunit (Sandhoff disease) of Hex A. Hex B (?? homodimer) is also defective in Sand- hoff disease. We previously developed mouse models of both diseases and

Jing-Qi Huang; Jacquetta M. Trasler; Suleiman Igdoura; Jean Michaud; Nobuo Hanai; Roy A. Gravel

1997-01-01

213

Neural precursor cell cultures from GM2 gangliosidosis animal models recapitulate the biochemical and molecular hallmarks of the brain pathology.  

PubMed

In this work we showed that genotype-related patterns of hexosaminidase activity, isoenzyme composition, gene expression and ganglioside metabolism observed during embryonic and postnatal brain development are recapitulated during the progressive stages of neural precursor cell (NPC) differentiation to mature glia and neurons in vitro. Further, by comparing NPCs and their differentiated progeny established from Tay-Sachs (TS) and Sandhoff (SD) animal models with the wild-type counterparts, we studied the events linking the accumulation of undegraded substrates to hexosaminidase activity. We showed that similarly to what observed in brain tissues in TS NPCs and progeny, the stored GM2 was partially converted by sialidase to GA2, which can be then degraded in the lysosomes to its components. The latter can be used in a salvage pathway for the formation of GM3. Interestingly, results obtained from ganglioside feeding assays and from measurement of lysosomal sialidase activity suggest that a similar pathway might work also in the SD model. PMID:19166507

Martino, Sabata; di Girolamo, Ilaria; Cavazzin, Chiara; Tiribuzi, Roberto; Galli, Rossella; Rivaroli, Anna; Valsecchi, Manuela; Sandhoff, Konrad; Sonnino, Sandro; Vescovi, Angelo; Gritti, Angela; Orlacchio, Aldo

2009-04-01

214

White Matter Changes Associated with Feline GM2 Gangliosidosis (Sandhoff Disease): Correlation of MR Findings with Pathologic and Ultrastructural Abnormalities  

Microsoft Academic Search

PURPOSE: To establish changes on MR of the brain in a feline model of Sandhoff disease in order to develop standards by which this model may be used in future noninvasive studies. METHODS: Five affected felines and six age-matched, littermate controls were evaluated. T1- and T2-weighted images were obtained once or twice for each of four affected and five control

Robert A. Kroll; Michael A. Pagel; Simon Roman-Goldstein; A. James Barkovich; Anthony N. D'Agostino; Edward A. Neuwelt

1995-01-01

215

Patient Education Thesaurus.  

ERIC Educational Resources Information Center

This thesaurus was compiled to make the materials in the Patient Education Room of the Donald J. Vincent Medical Library at Riverside Methodist Hospital, Columbus, Ohio, more accessible to patients. Subjects are grouped in fairly broad categories (e.g., Aging & Problems of Aging; Alcohol & Alcohol Abuse; Careers in the Medical Field; Childhood and…

Cooper, Lynn

216

Do patients have duties?  

PubMed Central

The notion of patients' duties has received periodic scholarly attention but remains overwhelmed by attention to the duties of healthcare professionals. In a previous paper the author argued that patients in publicly funded healthcare systems have a duty to participate in clinical research, arising from their debt to previous patients. Here the author proposes a greatly extended range of patients' duties grounding their moral force distinctively in the interests of contemporary and future patients, since medical treatment offered to one patient is always liable to be an opportunity cost (however justifiable) in terms of medical treatment needed by other patients. This generates both negative and positive duties. Ten duties—enjoining obligations ranging from participation in healthcare schemes to promoting one's own earliest recovery from illness—are proposed. The characteristics of these duties, including their basis, moral force, extent and enforceability, are considered. They are tested against a range of objections—principled, societal, epistemological and practical—and found to survive. Finally, the paper suggests that these duties could be thought to reinforce a regrettably adversarial characteristic, shared with rights?based approaches, and that a preferable alternative might be sought through the (here unexplored) notion of a “virtuous patient” contributing to a problem?solving partnership with the clinician. However, in defining and giving content to that partnership, there is a clear role for most, if not all, of the proposed duties; their value thus extends beyond the adversarial context in which they might first be thought to arise. PMID:18055897

Evans, H M

2007-01-01

217

Management of elderly patients  

PubMed Central

Summary Elderly patients are often excluded from clinical trials, yet more than two-thirds of patients diagnosed with lung cancer are over 65 years old. It is therefore important to develop specific tools and trials for this specific patient population. Methods This chapter first examines the management specificities of elderly patients. Randomized trials specifically involving elderly patients are then described, and likely future developments are considered. Results Older people have several specificities. In addition to traditional criteria such as age and performance status, other important factors include the number of comorbidities and age-related changes such as cognitive deficits and depression. Specific indices taking these factors into account have been published and validated. Single-agent therapy has been widely used to treat metastatic lung cancer in the elderly, following publication of negative results from randomized phase III trials of combination chemotherapy. Recently, however, a trial of doublet therapy gave positive results, in a subgroup of independent older patients. The benefit of patient selection based on a combination of these indices has been demonstrated in open-label and randomized trials. These results must now be confirmed in phase III trials including the use of tyrosine kinase inhibitors combined with chemotherapy. Conclusions Indices based on a combination of age-related factors, together with judicious use of biological markers, will further improve the prognosis of elderly lung cancer patients.

Corre, Romain; Lena, Hervé; Le Caer, Hervé

2013-01-01

218

Communicating with patients.  

PubMed

Dental care providers need to be able to communicate effectively with their patients in order to build rapport and trust. Highly developed communication skills also enable the dental care provider to extract more accurate diagnostic information and to more effectively present treatment options to the patient. Neurolinguistic programming techniques can be employed to accomplish these as well as other objectives. PMID:10687469

Kaplowitz, G J

1999-01-01

219

Student Clinic Patient Benefits  

E-print Network

-8770. After-Hours Care In the event of a dental emergency during non-clinic hours, please contact your student their medical or dental health and information contained in their patient record. · emergency care provided by dental hygienists and general dentists, patients also have access to on-site specialists

220

Briefing of Orthodontic Patients  

Microsoft Academic Search

The aim of this study was to record the level of relevant knowledge among orthodontic patients and their parents in order to determine how they prepare for the first consultation and what level of orthodontic briefing is needed. The focus was on the response of young patients to briefing, with other objectives being to investigate what briefing media are used

Anastasia Chatziandroni-Frey; Christos Katsaros; Rolf Berg

2000-01-01

221

Threading together patient expertise.  

PubMed

Patients are valuable sources of expertise for other patients in similar situations, but little is understood about the nature of this expertise. To address this knowledge gap, we investigated informational support as a mechanism for peers to help one another learn to cope with the breast cancer experience. We analyzed the types of problems discussed and recommendations offered by correspondents in three online breast cancer communities. Informational support was prevalent and directed towards problems in which correspondents were planning for future events or coping with emergent situations. Peers shared a wealth of patient expertise, including action strategies, recommended knowledge, suggested approaches, and information resources for dealing with problems. Our results highlight how peers are helping one another to learn. These findings bring insight to new support we could provide to patients for developing and sharing patient expertise, such as problem-based information organization and functionality for collaborative problem solving. PMID:18693814

Civan, Andrea; Pratt, Wanda

2007-01-01

222

[Involving patients in research].  

PubMed

Politics advocate the integration of patients in decision making processes as a means of individual participation. Patients' participation in research projects is a next step to fulfil this democratic goal.Concepts essential for rehabilitation are introduced that are germane in the context of participatory rehabilitation research. They are based on the results of 2 workshops where researchers, patients and those working in the field developed ideas for patients' participation in research and on a screening of relevant literature. Research traditions relevant for rehabilitation research are lined out, a stage model allowing design and documentation of patient participation is introduced, and recommendations for practice are given. The article ends with a list of open questions that need to be addressed in the future. PMID:23235946

Kirschning, S; Pimmer, V; Matzat, J; Brüggemann, S; Buschmann-Steinhage, R

2012-12-01

223

Approach to bleeding patient  

PubMed Central

Managing a bleeding patient is very challenging for the perioperative physician. Bleeding in a patient would be due to inherited or acquired disorders of haemostasis. Identifying the patients at risk of bleeding and utilising prophylactic treatment protocols has good outcomes. Along with clinical signs, trends in monitoring coagulation parameters and analysing blood picture are necessary. Management of patients in the postoperative period and in intensive care unit should be focused on normalization of coagulation profile as early as possible with available blood and its products. Available recombinant factors should be given priority as per the approved indications. Exploring the surgical site should be considered for persistent bleeding because haemodynamic compromise, excessive transfusion of fluids, blood and its products and more inotropic support may have a negative impact on the patient outcome. PMID:25535422

Gopinath, Ramachandran; Sreekanth, Y.; Yadav, Monu

2014-01-01

224

Threading Together Patient Expertise  

PubMed Central

Patients are valuable sources of expertise for other patients in similar situations, but little is understood about the nature of this expertise. To address this knowledge gap, we investigated informational support as a mechanism for peers to help one another learn to cope with the breast cancer experience. We analyzed the types of problems discussed and recommendations offered by correspondents in three online breast cancer communities. Informational support was prevalent and directed towards problems in which correspondents were planning for future events or coping with emergent situations. Peers shared a wealth of patient expertise, including action strategies, recommended knowledge, suggested approaches, and information resources for dealing with problems. Our results highlight how peers are helping one another to learn. These findings bring insight to new support we could provide to patients for developing and sharing patient expertise, such as problem-based information organization and functionality for collaborative problem solving. PMID:18693814

Civan, Andrea; Pratt, Wanda

2007-01-01

225

Approach to bleeding patient.  

PubMed

Managing a bleeding patient is very challenging for the perioperative physician. Bleeding in a patient would be due to inherited or acquired disorders of haemostasis. Identifying the patients at risk of bleeding and utilising prophylactic treatment protocols has good outcomes. Along with clinical signs, trends in monitoring coagulation parameters and analysing blood picture are necessary. Management of patients in the postoperative period and in intensive care unit should be focused on normalization of coagulation profile as early as possible with available blood and its products. Available recombinant factors should be given priority as per the approved indications. Exploring the surgical site should be considered for persistent bleeding because haemodynamic compromise, excessive transfusion of fluids, blood and its products and more inotropic support may have a negative impact on the patient outcome. PMID:25535422

Gopinath, Ramachandran; Sreekanth, Y; Yadav, Monu

2014-09-01

226

Interruption and patient satisfaction in resident-patient  

E-print Network

Interruption and patient satisfaction in resident-patient consultations Han Z. Li University categories of interruptions and patient satisfaction. Design/methodology/approach ­ A total of 40 resident/patient of interruptions, providing unequivocal support for communication accommodation theory. Patient satisfaction

Northern British Columbia, University of

227

Respecting patient confidentiality.  

PubMed

Nurses face a particular challenge in respecting the confidentiality of patients in a world where information is quickly shared and where information about illness can be sensitive. We have a duty of care towards patients. That duty includes maintaining privacy (protecting them from undue intrusion), and confidentiality (by the discreet management of information about themselves that they share with us). Legislation on confidentiality comes from different sources and should be interpreted in the clinical setting. This article summarises the principal requirements set out in the legislation and directs readers to questions and tools designed to help them explore the extent to which patient confidentiality is respected where they work. PMID:25627535

Price, Bob

2015-01-28

228

JAMA Patient Page: Meningitis  

MedlinePLUS

... of the American Medical Association JAMA PATIENT PAGE Meningitis M eningitis (infection of the coverings of the ... about meningitis in children. SIGNS AND SYMPTOMS OF MENINGITIS FOR MORE INFORMATION • National Institute of Neurological Disorders ...

229

JAMA Patient Page: Chemotherapy  

MedlinePLUS

... Treatment 2013. New York, NY: McGraw-Hill; 2013. Conflict of Interest Disclosures: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. The JAMA Patient Page ...

230

JAMA Patient Page: Malaria  

MedlinePLUS

... of the American Medical Association JAMA PATIENT PAGE Malaria M alaria is a potentially deadly disease caused ... the parasite. According to the World Health Organization, malaria is present in more than 100 countries—mostly ...

231

JAMA Patient Page: Osteoporosis  

MedlinePLUS

... reserved. JAMA PATIENT PAGE| Bones, Joints, and Muscles Osteoporosis Osteoporosis is the most common bone disease and is ... common in women as in men. People with osteoporosis have thinning of their bones, causing their bones ...

232

Patient & Family Support Programs  

E-print Network

Patients and supporters welcome. Support Services Room, Level 3, NCCC Pancreatic Cancer Support Group May with Pancreatic Cancer Action Network Support Services Room, Level 3, NCCC PSA at NCCC: Prostate Support Alliance

Myers, Lawrence C.

233

Understanding Patient Safety Confidentiality  

MedlinePLUS

... care quality issues. To encourage the reporting and analysis of medical errors, PSQIA provides Federal privilege and ... information collected and created during the reporting and analysis of patient safety events. The confidentiality provisions will ...

234

JAMA Patient Page: Insomnia  

MedlinePLUS

... of the American Medical Association JAMA PATIENT PAGE Insomnia I nsomnia (trouble falling asleep or staying asleep) ... 21, 2003, issue of JAMA. POSSIBLE CAUSES OF INSOMNIA FOR MORE INFORMATION • National Sleep Foundation www.sleepfoundation. ...

235

JAMA Patient Page: Glaucoma  

MedlinePLUS

... damages the major nerve of the eye (the optic nerve ) and eventually may cause permanent vision loss. ... pressure in the eye and eventually damage the optic nerve. Some patients with open-angle glaucoma do ...

236

JAMA Patient Page: Concussion  

MedlinePLUS

... PATIENT PAGE Concussion C oncussion (or mild traumatic brain injury) is a brain injury caused by blunt head trauma. In the United ... these symptoms could indicate development of more serious brain injury. PREVENTION Attention to safety, making your home safe, ...

237

JAMA Patient Page: Shingles  

MedlinePLUS

... of the American Medical Association JAMA PATIENT PAGE Shingles S hingles is a painful condition caused by the ... the United States alone. Shingles, also known as herpes zoster , occurs in persons who have already had chickenpox. ...

238

An Electronic Patient Record \\  

Microsoft Academic Search

By nature, an electronic patient record (EPR) [9] consists of many pieces owned and managed by dif-ferent entities: yourself as a patient, your referring doctor, the various specialists you are dealing with (e. g. gynecologist, optometrist, physical therapist), the pharmacist(s) you shop from, the various hospi-tals you go to for surgery or special examination, the insurance company (private or state-owned)

Serge Abiteboul; Bogdan Alexe; Omar Benjelloun; Bogdan Cautis; Irini Fundulaki; Tova Milo; Arnaud Sahuguet

2004-01-01

239

The Immunocompromised Patient  

PubMed Central

The number of immunocompromised persons—as well as the importance of family physicians understanding their state—is increasing. In many instances the family physician will first identify or provide day-to-day care for such patients while they live in the community. This article gives an overview of certain aspects of normal host immunity, etiology and mechanisms in immunocompromisation, and outlines techniques for recognition and management of this special group of patients. PMID:21263824

Mahon, J.L.; Stiller, C.R.

1987-01-01

240

Predictors of patient satisfaction  

Microsoft Academic Search

Correlates of patient satisfaction at varying points in time were assessed using a survey with 2-week and 3-month follow-up in a general medicine walk-in clinic, in USA. Five hundred adults presenting with a physical symptom, seen by one of 38 participating clinicians were surveyed and the following measurements were taken into account: patient symptom characteristics, symptom-related expectations, functional status (Medical

Jeffrey L. Jackson; Judith Chamberlin; Kurt Kroenke

2001-01-01

241

Patient characteristics and fairness  

Microsoft Academic Search

This study examines the fairness concept of health care professionals, and asks whether they are willing to use a patient’s\\u000a age and other potential fairness characteristics rather than health benefits as relevant arguments in the allocation of health\\u000a care resources? The patient characteristics in the health care professionals’ survey encompass age, productivity and lifestyle.\\u000a The study is a replication of

Hannu Valtonen

2009-01-01

242

[A 'lucky' patient].  

PubMed

A 72-year-old male diabetic patient admitted to our operative unit of nephrology and dialysis underwent hemodialytic treatment because of rapidly progressive renal failure. A moderate hypertensive state was associated to nephrotic proteinuria and microematuria. Renal angiography showed a severe stenosis of the right renal artery and a smaller left kidney. Right renal artery stenting induced a significant reduction in serum creatinine (Cr) and the patient discontinued with the dialytic treatment. PMID:15786378

Lusenti, T; Rustichelli, R; Cardarelli, F; Pavone, L; Borgatti, P P; Manari, A; Fioroni, S; Giacometti, P; Tirabassi, G; Guiducci, V

2005-01-01

243

White coat, patient gown.  

PubMed

Much has been written about the symbolic function of the white coat: its implications of purity, its representation of authority and professionalism, and its role in consolidating a medical hierarchy. By contrast, the medical literature has paid almost no attention to the patient gown. In this article, we argue that in order to understand the full implications of the white coat in the doctor-patient relationship, we must also take into account patients' dress, and even undress. We explore contemporary artistic images of white coat and patient gown in order to reveal the power differential in the doctor-patient relationship. Artistic representations capture some of the cultural ambivalence surrounding the use of the white coat, which confers professional status on its wearer, while undermining his or her personal identity. At the other end of the sartorial spectrum, hospital gowns also strip wearers of their identity, but add to this an experience of vulnerability. Although compelling reasons for continuing to wear the white coat in circumscribed settings persist, physicians should be mindful of its hierarchical implications. Ample room remains for improving patients' privacy and dignity by updating the hospital gown. PMID:24687912

Wellbery, Caroline; Chan, Melissa

2014-12-01

244

Choosing effective patient education materials  

MedlinePLUS

Your patient's preferences can guide your choice of education materials and methods. Find out how your patient ... aware that you may need to adjust your education plan based on the patient's health status and ...

245

Cancer Patients and Fungal Infections  

MedlinePLUS

... About CDC.gov . Fungal Diseases Share Compartir Cancer Patients and Fungal Infections As a cancer patient, you ... Top of Page Preventing fungal infections in cancer patients Fungi are difficult to avoid because they are ...

246

[Patients and solicitude].  

PubMed

Patients are not only passive and vulnerable beings who need to be cared for. They are also autonomous, active and capable of caring for others as well as for themselves. In this study, the author has completed lengthy interviews with five women in order to identify different types of caring. Complicity-based caring is characterized by verbal and nonverbal behavior of patients who are sharing a common experience. This type of caring can be encouraged by a third-party who brings patients together with similar experiences. Action-oriented caring consists of intervening for other patients as an antidote for one's own fear, panic and anguish. Solidarity-based caring corresponds with assisting fellow patients in finding and maintaining their own identity, pride and dignity. Co-operative caring can be observed in group-type settings such as the behavior observed during support groups or vegetarian cooking classes for cancer patients. Self-centred caring refers to the various forms of concern one has for one's self. The experience of suffering can determine how caring is expressed. Concern can force individuals to examine their way of acting and interacting more carefully. Conscious choices are made to avoid empty and exhausting relationships and encourage the growth of positive relationships. Paradoxically, this change in perspective brings about an open mind and heart. It is at this time that caring for healthy individuals appears. Unfortunately, there is very little distinction between patients and healthy individuals, but rather sensitive relationships between individuals facing difficult life challenges. PMID:1394073

Lettre, L

1992-08-01

247

JAMA Patient Page  

NSDL National Science Digital Library

The Journal of the American Medical Association (JAMA) has been committed to providing the general public with a number of high-quality print and online resources in recent years, and their collection of Patient Pages is quite thorough and most welcome. With over 390 entries, each Patient Page contains a basic overview of such topics as Lyme disease, dementia, lymphoma, and dozens of other conditions, medical procedures, and practices. Along with succinct and accessible summaries for each entry, visitors will also find illustrations, graphs, and diagrams that help explain each topic. All in all, this site is a tremendous resource, and it is worth noting that many of these Patient Pages are also available in Spanish.

248

Patient Safety Network  

NSDL National Science Digital Library

The Agency for Healthcare Research and Quality (AHRQ) Patient Safety Network (PSNet) website contains recent news and resources to provide those studying to be in the medical profession and for those currently in the medical field. Resources include an extensive glossary as well as a vast supply of articles from various periodicals. The site also contains numerous �Did You Know?� articles that include visual aids and citations. Articles can be sorted or browsed by target audience, resource type, clinical area, error type, safety target, approach to improving safety, and setting of care. Users have the ability to sign up for the weekly AHRQ Patient Safety Network and monthly AHRQ Web Morbidity and Mortality (WEBM&M) newsletters. Users may also sign up for a free account on the AHRQ Patient Safety Network website to receive e-mail alerts that match the users' interests.

249

Mental patients in prisons.  

PubMed

Mental conditions usually affect cognitive, emotional and volitional aspects and functions of the personality, which are also functions of interest in law, as they are essential at the time of adjudicating guilt, labeling the accused a criminal, and proffering a sentence. A relationship between mental illness and criminality has, thus, been described and given as one of the reasons for the large number of mental patients in prisons. Whether this relationship is one of causality or one that flows through many other variables is a matter of debate, but there is no debating that prisons have become a de facto part, and an important one, of mental health systems in many countries. This paper deals with the issue of the relationship and provides estimates of prevalence of mental patients in prisons culled from many studies in different countries. It also provides some direction for the management of mental patients as they crowd correctional systems. PMID:19812758

Arboleda-Flórez, Julio

2009-10-01

250

Black patients receive less clinical trial information than white patients  

Cancer.gov

A study from the Wayne State University School of Medicine and the Barbara Ann Karmanos Cancer Institute comparing how physicians discuss clinical trials during clinical interactions with black patients versus white patients further confirms racial disparities in the quality of communication between physicians and patients. Oncologists provided black patients with less information overall about cancer clinical trials compared with white patients, according to data presented at the Fifth AACR Conference on The Science of Cancer Health Disparities, Oct. 27-30, 2012.

251

Listening to older patients.  

PubMed

This article presents findings from focus-group research conducted by Age Wave, Inc., a marketing services, research and consulting firm focusing on the 50+ market. The research is part of a comprehensive study on the aging-readiness of acute-care hospitals, sponsored by Baxter Healthcare Corporation. The findings discussed here are based on focus groups conducted in April 1993 with recently discharged 50+ patients in 10 major metropolitan/nonmetropolitan areas throughout the country. While findings from focus groups should be considered directional rather than absolute, the views of an expert panel confirm many of the observations and experiences of these older hospital patients. PMID:10129188

Kane, V L

1993-01-01

252

Patient Satisfaction: Improving HCAHPS scores  

E-print Network

Patient Satisfaction: Improving HCAHPS scores in the Johns Hopkins Hospital Department of Medicine. Patient satisfaction is an important aspect of patient care and is progressively being utilized, patient satisfaction scores are becoming a point of contingency for reimbursement for services. Achieving

von der Heydt, Rüdiger

253

User interface and patient involvement.  

PubMed

Increased patient involvement is a goal in contemporary health care, and of importance to the development of patient oriented ICT. In this paper we discuss how the design of patient-user interfaces can affect patient involvement. Our discussion is based on 12 semi-structured interviews with patient users of a web-based solution for patient--doctor communication piloted in Norway. We argue ICT solutions offering a choice of user interfaces on the patient side are preferable to ensure individual accommodation and a high degree of patient involvement. When introducing web-based tools for patient--health professional communication a free-text option should be provided to the patient users. PMID:23823362

Andreassen, Hege Kristin; Lundvoll Nilsen, Line

2013-01-01

254

Patient safety: a consumer's perspective.  

PubMed

In this article we provide a reconceptualization of patient-centered health care practice through a collaborative person-centered model for enhanced patient safety. Twenty-one participants were selected and interviewed from the internationally diverse population of individuals attending the Chicago Patient Safety Workshop (CPSW) sponsored by Consumers Advancing Patient Safety (CAPS). Analysis of the participant transcripts revealed three findings related to patient experience: the impact and meaning of communication and relationship within the health care setting, trust and expectation for the patient and family with the health care provider, and the meaning and application of patient-centeredness. Researchers concluded that successful planning toward enhanced patient-centered care requires multiple perspectives, including the voices of the patient and family members who have experienced the trauma of preventable medical error. Collaborative initiatives such as the CPSW and CAPS offer a positive way forward for enhanced patient safety and quality of care. PMID:21343433

Hovey, Richard B; Dvorak, Mitchell L; Burton, Tessa; Worsham, Sherry; Padilla, James; Hatlie, Martin J; Morck, Angela C

2011-05-01

255

Patient-centered Care & Communication  

Cancer.gov

Patient-centeredness is increasingly being recognized as a critical indicator of high-quality health care delivery. Although several definitions of patient-centeredness have been proposed in the literature, two attributes are considered central to the delivery of patient-centered care. These attributes are being responsive to patient needs and incorporating the patient's perspective and experiences in care planning and decision-making.

256

Assessing Patients’ Health Behaviours  

Microsoft Academic Search

This chapter provides a summary of various approaches to behaviour change in oral health. The current research evidence does not support the practice of giving ‘instructions’ or ‘advice’ to patients as a means of modifying their attitudes or changing their health behaviours. A number of explanatory models are described which address both the complexity and the factors that influence and

Ruth Freeman; Amid Ismail

2009-01-01

257

Prognosis of patients with \\  

Microsoft Academic Search

All 662 patients admitted to the two coronary care units in Nottingham during 12 consecutive months were followed up prospectively for one year. At the time of discharge from hospital they were categorised according to set criteria into the following diagnostic groups: definite, probable, or possible myocardial infarction; ischaemia heart disease without infarction; chest pain ?cause; and other diagnoses. Eighty-nine

R G Wilcox; J M Roland; J R Hampton

1981-01-01

258

Patients' Bill of Rights  

NSDL National Science Digital Library

The Senate debate on what has come to be known as the "Patients' Bill of Rights" is the focus of this week¹s In the News. The call for legislation of this type has garnered increased attention and support over the past two years as complaints have mounted over the often unappealable decisions of HMOs to deny coverage or restrict access. While both Democrats and Republicans favor such legislation, there are key differences between the two parties' approaches. Republicans have offered a bill that establishes an independent medical reviewer for insured patients denied coverage, while Democrats favor giving patients expanded litigation options as a way to discipline HMOs. Democrats also want to see legislation that returns the ultimate decision on medical treatment to the patient's physician. Republicans disagree with this approach, seeing it as a return to the cost problems that generated the widespread need for HMOs originally. Finally, the Republican version of this legislation promises full protection only to Federal employees as GOP legislators argue the states already protect private employees.

Charbonneau, David D.

259

Chronic Illness and Patient Satisfaction  

PubMed Central

Objective To examine how the relationship between patient characteristics, patient experience with the health care system, and overall satisfaction with care varies with illness complexity. Data Sources/Study Setting Telephone survey in 14 U.S. geographical areas. Study Design Structural equation modeling was used to examine how relationships among patient characteristics, three constructs representing patient experience with the health care system, and overall satisfaction with care vary across patients by number of chronic illnesses. Data Collection/Extraction Methods Random digital dial telephone survey of adults with one or more chronic illnesses. Principal Findings Patients with more chronic illnesses report higher overall satisfaction. The total effects of better patient–provider interaction and support for patient self-management are associated with higher satisfaction for all levels of chronic illness. The latter effect increases with illness burden. Older, female, or insured patients are more satisfied; highly educated patients are less satisfied. Conclusions Providers seeking to improve their patient satisfaction scores could do so by considering patient characteristics when accepting new patients or deciding who to refer to other providers for treatment. However, our findings suggest constructive actions that providers can take to improve their patient satisfaction scores without selection on patient characteristics. PMID:22515159

Carlin, Caroline S; Christianson, Jon B; Keenan, Patricia; Finch, Michael

2012-01-01

260

Building an effective doctor-patient relationship: From patient satisfaction to patient participation  

Microsoft Academic Search

In this paper, the authors argue that patient satisfaction is an insufficient measure of the quality of the doctor-patient relationship. While shown to have a salutary effect on patient anxiety concerning illness and treatment, the only other significant outcome associated with levels of satisfaction is utilization behavior. This is not surprising, the authors argue, since prevailing conceptualizations of patient satisfaction

Edward J. Speedling; David N. Rose

1985-01-01

261

Association of patient-reported care coordination with patient satisfaction.  

PubMed

Little is known about the relationship between care coordination directly assessed from the patient's perspective and patient satisfaction. This study applied multiple logistic regression models to examine associations between patient-reported care coordination and patient satisfaction among 1367 patients with diabetes. We found robust positive relationship between care coordination and patient satisfaction with overall chronic care (odds ratio [OR] = 1.78), one's regular doctor (OR = 1.85), and the way care was organized (OR = 1.98). Implications for health plans, providers, and future research are discussed. PMID:25469580

Wang, Margaret C; Mosen, David; Shuster, Elizabeth; Bellows, Jim

2015-01-01

262

Mucormycosis in immunochallenged patients.  

PubMed

Mucorales species are deadly opportunistic fungi with a rapidly invasive nature. A rare disease, mucormycosis is most commonly reported in patients with diabetes mellitus, because the favorable carbohydrate-rich environment allows the Mucorales fungi to flourish, especially in the setting of ketoacidosis. However, case reports over the past 20 years show that a growing number of cases of mucormycosis are occurring during treatment following bone marrow transplants (BMT) and hematological malignancies (HM) such as leukemia and lymphoma. This is due to the prolonged treatment of these patients with steroids and immunosuppressive agents. Liposomal amphotericin B treatment and posaconazole are two pharmacologic agents that seem to be effective against mucormycosis, but the inherently rapid onset and course of the disease, in conjunction with the difficulty in correctly identifying it, hinder prompt institution of appropriate antifungal therapy. This review of the literature discusses the clinical presentation, diagnosis, and treatment of mucormycosis among the BMT and HM populations. PMID:19561989

Pak, Jane; Tucci, Veronica T; Vincent, Albert L; Sandin, Ramon L; Greene, John N

2008-07-01

263

[Pylephlebitis in pediatric patients].  

PubMed

Pylephlebitis is defined as thrombophlebitis of the portal vein or its tributaries. It is a rare disease commonly associated with acute appendicitis and it has a high rate of morbidity and mortality. Doppler ultrasound and computed tomography scan are the methods of choice to confirm diagnosis. The most frequent long-term complication in these patients is portal vein cavernoma, with subsequent portal hypertension. An early diagnosis, timely antibiotic therapy and removal of infection are essential therapeutic measures to diminish mortality. The need for anticoagulation therapy in children remains controversial. We report on a child with acute abdomen and sepsis with a diagnosis of pylephlebitis secondary to appendiceal inflammation. The patient received long-term antibiotic therapy and subcutaneous anticoagulation. Deferred appendectomy was performed with favorably outcome. PMID:24955918

Degano, Lucas Alberto; El Kik, Soraya Anis; Rizzi, Ana

2014-08-01

264

[A dissociative patient].  

PubMed

A 45-year-old woman attended a centre for special dental care. Initially, it seemed that the patient suffered from an extreme form of dental anxiety. However, the fact that she displayed 'dissociations' suggested that she had a severe psychiatric disorder, in this case Dissociative Identity Disorder. The key feature of this condition is a dysfunction of the normal integrative functions of identity, memory and consciousness. In such instances it is recommended to contact a psychologist or psychiatrist and the referring care provider to consider the consequences of the psychiatric condition regarding informed consent, treatment plan and actual treatment. Because it was not likely that the patient would respond to an intervention specifically aimed to reduce anxiety in the dental setting, dental treatment under general anesthesia was the best suited option. PMID:19739405

de Jongh, A; Abkhezr, S; Broers, D L M

2009-08-01

265

Patient Preparation and Tagging  

Microsoft Academic Search

\\u000a Computed tomographic colonography (CTC) has become widely used over the past decade as a complementary method for colorectal\\u000a cancer screening. Achieving consistently high performance with the examination depends on the quality of a number of factors,\\u000a including: patient preparation prior to the examination, colonic distension, computed tompgraphic (CT) scanning parameters\\u000a and data acquisition, postprocessing of data, 2D and 3D navigation

Dipti K. Lenhart; Rocio Perez Johnston; Michael E. Zalis

266

Hyperkalemia in hospitalized patients  

Microsoft Academic Search

Objective: Evaluate the prevalence of hyperkalemia(potassium < 5.5 mmol\\/l) in hospitalized patientsnot on dialysis, as well as the association\\u000a ofmedications, impaired renal function and comorbidconditions with hyperkalemia.Design: A retrospective case-control method.Setting: A tertiary care teaching hospital.Patients: Hyperkalemic adults not on dialysis withage and sex matched controls.Interventions: None.Main outcome measures: The use of medicationsassociated with hyperkalemia and renal function usinga calculated

Robert W. Dunlay; Marc S. Stevens

2000-01-01

267

[When patients become models].  

PubMed

In order to boost the self-esteem of patients suffering from cancer and to present the public with a different image of the disease, the Ouest oncology institute of Angers organized a fashion show. Lengthy preparations enabled these models-for-a-day to feel at ease on the catwalk and draw a real benefit from the whole experience. Amid the success and emotion, they were able to forget, for a moment, their disease. PMID:24624723

Lecomte, Cyriaque

2014-01-01

268

[Prediction of patient outcome].  

PubMed

Monitoring biomedical signals obtained from a patient generates information that processed conveniently, it has to allow detecting as soon as possible changes in the predicted evolution. The systematic register of one of these biomedical signals is named a time series. In this paper, a brief introduction appears to the Box-Jenkins methodology applied to time series analysis and it is applied this methodology to an example as illustration. PMID:14980160

Muñoz Gracia, M Pilar

2004-01-01

269

Patient Safety in Surgery  

PubMed Central

Background: Improving patient safety is an increasing priority for surgeons and hospitals since sentinel events can be catastrophic for patients, caregivers, and institutions. Patient safety initiatives aimed at creating a safe operating room (OR) culture are increasingly being adopted, but a reliable means of measuring their impact on front-line providers does not exist. Methods: We developed a surgery-specific safety questionnaire (SAQ) and administered it to 2769 eligible caregivers at 60 hospitals. Survey questions included the appropriateness of handling medical errors, knowledge of reporting systems, and perceptions of safety in the operating room. MANOVA and ANOVA were performed to compare safety results by hospital and by an individual's position in the OR using a composite score. Multilevel confirmatory factor analysis was performed to validate the structure of the scale at the operating room level of analysis. Results: The overall response rate was 77.1% (2135 of 2769), with a range of 57% to 100%. Factor analysis of the survey items demonstrated high face validity and internal consistency (? = 0.76). The safety climate scale was robust and internally consistent overall and across positions. Scores varied widely by hospital [MANOVA omnibus F (59, 1910) = 3.85, P < 0.001], but not position [ANOVA F (4, 1910) = 1.64, P = 0.16], surgeon (mean = 73.91), technician (mean = 70.26), anesthesiologist (mean = 71.57), CRNA (mean = 71.03), and nurse (mean = 70.40). The percent of respondents reporting good safety climate in each hospital ranged from 16.3% to 100%. Conclusions: Safety climate in surgical departments can be validly measured and varies widely among hospitals, providing the opportunity to benchmark performance. Scores on the SAQ can serve to evaluate interventions to improve patient safety. PMID:16632997

Makary, Martin A.; Sexton, J Bryan; Freischlag, Julie A.; Millman, E Anne; Pryor, David; Holzmueller, Christine; Pronovost, Peter J.

2006-01-01

270

Measuring Patient Satisfaction  

Microsoft Academic Search

The past three decades have seen an evolution in the evaluation of cancer care. Supply has made a determined effort to catch\\u000a up with the demand for a more comprehensive assessment of factors that ascertain quality of care, striving to provide better\\u000a service to a consumer-driven society. This is mainly the result of patients becoming more knowledgeable and savvy to

Arvin Koruthu George; Martin G. Sanda

271

[Transplant patient monitoring].  

PubMed

Management of transplant recipients consists in a good balance between an optimal graft function and the potential toxic effects of immunosuppressive drugs. Indeed, transplant patient monitoring has to be very meticulous and includes repetitive clinical, biological and morphological tests. Acute or chronic graft dysfunctions should be identified very soon in order to confirm diagnosis by pathologic analyses and to adapt the immunosuppressive treatment. On the other hand, the complications occurring in transplant patients have to be diagnosed promptly to start an optimal treatment without delay. The main complications are: infectious (conventional infections in the first month and opportunist infections thereafter [CMV, pneumocystosis, toxoplasmosis, aspergillosis...]); cardio-vascular because of numerous cardio-vascular risk factors occurring after transplantation: hypertension, hyperlipidemia, diabetes...; neoplasic with a major increase of lymphomas and cutaneous carcinomas incidences after transplantation. A good management of transplant recipient leads to a prompt treatment of the complications, an improvement in graft and patient' survivals and an increase in their quality of life. PMID:17578031

Caillard, Sophie; Moulin, Bruno

2007-02-15

272

Therapeutic education of diabetic patients.  

PubMed

Therapeutic patient education is a patient-centred approach, focussed on patients' needs, resources, values and strategies. It allows patients to improve their knowledge and skills not only concerning their illness but also their treatment. It brings a better quality of life, a greater therapeutic compliance and a reduction in complications. The most difficult part of therapeutic patient education occurs when patients must change their behaviour. Motivational interviewing and cognitive-behavioural approaches contribute greatly here and allow both the preparation and support of patients during progressive 'step by step' change. The work on resistance to change is fundamental, and ambivalence when faced with the choice of a new way of life must be measured, discussed and negotiated. Patients become partners and we become 'coaches'. The negotiation of objectives must allow patients to choose their own strategies, which normally should cost them the least possible, psychologically, and bring them the maximum benefit. The efficiency of therapeutic patient education no longer needs to be proved: 80% less amputations over 10 years in diabetic patients; 50% maintenance of weight loss over 5 years, etc. In conclusion, therapeutic education is part of a humanistic medical approach centred on patients; it allows them to be active participants in their own treatment with the aim of improving their quality of life and therapeutic compliance, as well as reducing potential complications. Thus, health care professionals teach, inform, train, negotiate with, motivate and accompany patients in the long-term follow-up of their illness. PMID:18229887

Golay, A; Lagger, G; Chambouleyron, M; Carrard, I; Lasserre-Moutet, A

2008-01-01

273

Angle closure in younger patients.  

PubMed Central

PURPOSE: Angle-closure glaucoma is rare in children and young adults. Only scattered cases associated with specific clinical entities have been reported. We evaluated the findings in patients in our database aged 40 or younger with angle closure. METHODS: Our database was searched for patients with angle closure who were 40 years old or younger. Data recorded included age at initial consultation; age at the time of diagnosis; gender; results of slit-lamp examination, gonioscopy, and ultrasound biomicroscopy (from 1993 onward); clinical diagnosis; and therapy. Patients with previous incisional surgery were excluded, as were patients with anterior chamber proliferative mechanisms leading to angle closure. RESULTS: Sixty-seven patients (49 females, 18 males) met entry criteria. Mean age (+/- SD) at the time of consultation was 34.4 +/- 9.4 years (range, 3-68 years). Diagnoses included plateau iris syndrome (35 patients), iridociliary cysts (8 patients), retinopathy of prematurity (7 patients), uveitis (5 patients), isolated nanophthalmos (3 patients), relative pupillary block (2 patients), Weill-Marchesani syndrome (3 patients), and 1 patient each with Marfan syndrome, miotic-induced angle closure, persistent hyperplastic primary vitreous, and idiopathic lens subluxation. CONCLUSION: The etiology of angle closure in young persons is different from that in the older population and is typically associated with structural or developmental ocular anomalies rather than relative pupillary block. Following laser iridotomy, these eyes should be monitored for recurrent angle closure and the need for additional laser or incisional surgical intervention. PMID:12545694

Chang, Brian M; Liebmann, Jeffrey M; Ritch, Robert

2002-01-01

274

Patient Preference Methods - A Patient Centered Evaluation Paradigm  

Microsoft Academic Search

he increased focus on patient reported out- comes (PROs) in medical research in recent years has heightened the awareness of the patient's perspective of health outcomes. It is unclear, how- ever, if the use of PROs alone will lead us toward patient-centered care or if we need to rethink some of the foundations of our research methods in order to

John FP; F. Reed Johnson; A. Brett Hauber

2007-01-01

275

Patient Power? Medical Perspectives on Patient Use of the Internet  

Microsoft Academic Search

Patients and carers now have unprecedented access to health information via specialist journals and the popular media, while the worldwide web has revolutionised public access to clinical information. Levels of patient demand for information about health have grown and there is evidence to suggest that patients wish to receive more information than is sometimes currently provided by clinicians. In secondary

Jennifer Tann; Adrian Platts; Sarah Welch; Judy Allen

2003-01-01

276

Evaluation's Role in Patient Education  

ERIC Educational Resources Information Center

The most desirable outcome of any patient education program is a patient who is aware of medical alternatives and their potential effects and who chooses voluntarily and intelligently whether or not to follow medical advice. (MM)

Brown, Andrew J.

1977-01-01

277

JAMA Patient Page: Organ Donation  

MedlinePLUS

... of the American Medical Association JAMA PATIENT PAGE Organ Donation O rgan transplantation can be lifesaving for patients ... to meet the demand. The main factor limiting organ donation is that less than half of the families ...

278

Patient Initals University of Washington  

E-print Network

_________ Patient Initals University of Washington Patient Acknowledgement for Kidney Transplantation in Donor Exchange KIDNEY RECIPIENT You have been given the opportunity to participate in the Paired Kidney Donation Exchange program because you and your prospective kidney donor

Borenstein, Elhanan

279

Patient Care a Genetic Counselor  

E-print Network

Patient Care Advocacy Education Research Become a Genetic Counselor CENTER FOR Molecular Medicine in risk assessment, education, interpersonal communication, and counseling to provide services and Genetics in the School of Medicine. The Center's extraordinary faculty, internationally recognized patient

Berdichevsky, Victor

280

Patient Care a Genetic Counselor  

E-print Network

Patient Care Advocacy Education Research Become a Genetic Counselor Public Policy Center, and counseling theory with their skills in risk assessment, education, interpersonal communication, internationally recognized patient clinics, and state- of-the-art research laboratories uniquely integrate

Berdichevsky, Victor

281

Plastic Surgery for Ethnic Patients  

MedlinePLUS

... Asian face and maintains an almond shape. An African American patient interested in nose reshaping may want ... and hypertrophic scars are common in patients of African and Asian ancestry, for example, and appear as ...

282

Hospitalized Patients and Fungal Infections  

MedlinePLUS

... About CDC.gov . Fungal Diseases Share Compartir Hospitalized Patients and Fungal Infections Even though you’re staying ... Top of Page Preventing fungal infections in hospitalized patients Fungi are difficult to avoid because they are ...

283

Patient Safety Threat - Syringe Reuse  

MedlinePLUS

... About CDC.gov . Injection Safety Share Compartir A Patient Safety Threat – Syringe Reuse Important Information! Please read ... due to syringe reuse by your healthcare provider. Patients need to be aware of a very serious ...

284

Medical and Dental Patient Issues  

MedlinePLUS

... Join or Renew Members Only Medical and Dental Patient Issues The following FAQs have been developed by our topic editors for this category: Dental-Patient Issues Medical CT Reference Books and Articles on ...

285

Support for Patients and Families  

MedlinePLUS

Support for Patients and Families Explore this section for support and advocacy organizations that can help you share your story, connect ... and Lodging Assistance Disability Resources Evaluating Health Information Patient Advocacy Groups in the United States List of ...

286

Preventing Infections in Cancer Patients  

MedlinePLUS

... Publications Mold Stay Informed Cancer Home Information for Patients and Caregivers Language: English Español (Spanish) Recommend on Facebook Tweet Share Compartir Cancer patients who are treated with chemotherapy are more likely ...

287

The patient’s perspective on complications after spine surgery  

PubMed Central

Recent years have witnessed a paradigm shift in relation to the assessment of outcome in spine surgery: multidimensional patient-centred questionnaires have superseded traditional surgeon-based ratings of outcome, and surgical registries have been developed to capitalise on the principle of “strength in numbers.” However, the assessment of complications has not enjoyed this same enlightened patient-centred approach. The present study investigated post-surgical complications from the patient’s perspective. All German-speaking patients undergoing surgery within our Spine Center in 2005 were asked to complete the patient-orientated Core Measures Outcome Index of the SSE Spine Tango Spine Surgery Registry before and 12 months after surgery; the surgeon completed a Spine Tango surgery form. In the 12-month questionnaire, the patient was asked, “did any complications arise as a consequence of your operation 1 year ago (e.g. problems with wound healing, paralysis, sensory disturbances, etc.)? If so, give details.” Patients were also asked about their satisfaction with the operation and the global outcome of surgery. 1,035 patients were sent a 12-month questionnaire; 972 (94%) returned the completed questionnaire. 29% patients answered “yes” to the question about complications. The incidence of patient-rated complications was significantly associated with outcome/satisfaction (P < 0.05), suggesting these complications were not trivial to the patient. The results indicate that, just like outcome, “complications” should be assessed from both the patient’s and the surgeon’s perspectives, not least to better understand the reasons accounting for dissatisfaction and a poor patient-rated outcome. PMID:19390874

Grob, Dieter

2009-01-01

288

Pneumococcal bacteremia in cancer patients  

Microsoft Academic Search

Twenty-eight episodes of Streptococcus pneumoniae bacteremia occurring in 27 cancer patients hospitalized in the Institut Jules Bordet between July 1979 and April 1985 were reviewed. Ten patients had hematological malignancies and 17 had solid tumors (in 7 cases, of the lung). Forty-four per cent of the patients were neutropenic (<1000\\/µl) and 36% of the patients were in septic shock. In

V. Richard; F. Meunier; P. Auwera; P. Dejace; D. Daneau; J. Klastersky

1988-01-01

289

Preparing a patient information leaflet.  

PubMed

As a student of operating department practice, I was asked to produce a patient information leaflet that helped to prepare patients for a surgical procedure. In addition, I had to write a paper highlighting the issues involved in effectively communicating with vulnerable patients. The relevance of communication and information giving is vital in all aspects of healthcare but even more so in theatre where the patient must be informed to give consent. PMID:17139907

Brown, Valerie

2006-11-01

290

The physician-patient relationship revisited: the patient's view.  

PubMed

The importance of the physician-patient relationship for the health care market is beyond controversy. Recent work emphasizes a two-sided asymmetric information relationship between physician and patient. In contrast to most work looking only at the physician's perspective, our paper concentrates on the patient's view. Estimation results support the hypotheses that physician consultation and health relevant behavior are not stochastically independent. In the recursive bivariate probit model, patient's health relevant behavior has a significant influence on the probability of a physician visit. This means that health care demand and not only the contact decision is determined by both, patient and physician. PMID:18597172

Schneider, Udo; Ulrich, Volker

2008-12-01

291

Predicting outcome in ICU patients  

Microsoft Academic Search

Conclusions Considerable time and energy has been invested in the conception, modelling and evaluation of sophisticated severity scoring systems for ICU patients. These systems are created to enhance the precise estimation of hospital mortality for large ICU patient populations. Their current low sensitivity precludes their use for predicting out-come for individual ICU patients. However, severity scores can already be valuable

P. Suter; A. Armaganidis; F. Beaufils; X. Bonfill; H. Burchardi; D. Cook; A. Fagot-Largeault; L. Thijs; S. Vesconi; A. Williams; J. R. Le Gall; R. Chang

1994-01-01

292

Insomnia in Diabetic Hemodialysis Patients  

Microsoft Academic Search

Background: Insomnia is one of the most common problems in dialysis patients, and likely to contribute impairment in quality of life, which has a positive correlation with patients’ survival. In diabetic patients, morbidity and mortality are substantially higher than in the nondiabetic counterparts, and also the incidence of sleep disturbances. However, there is no means to predict sleep disturbance in

Sang-Youb Han; Jong-Woo Yoon; Sang-Kyung Jo; Jin-Ho Shin; Chol Shin; Jung-Bok Lee; Dae-Ryong Cha; Won-Yong Cho; Heui-Jung Pyo; Hyoung-Kyu Kim; Kyu-Bec Lee; Hyang Kim; Kyung-Wook Kim; Yong-Seop Kim; Jeong-Ho Lee; Sang-Eun Park; Chang-Soo Kim; Kyeong-So Wea; Kyung-Shik Oh; Tae-See Chung; Sang-Yeol Suh

2002-01-01

293

Strategies for enhancing patient compliance  

Microsoft Academic Search

Patient noncompliance is a substantial obstacle to the achievement of therapeutic goals. This paper reviews a number of practical interventions with demonstrated efficacy in enhancing patient adherence, including (1) improving patients' levels of information concerning the specifics of their regimens, reinforcing essential points with review, discussion, and written instruction, and emphasizing the importance of the therapeutic plan, (2) taking clinically

Marshall H. Becker; Lois A. Maiman

1980-01-01

294

Insomnia in maintenance haemodialysis patients  

Microsoft Academic Search

Background. Studies in the last 15 years have shown a high prevalence of sleep disorders in maintenance haemodialysis (HD) patients. Methods. To investigate whether the new technical and therapeutic advances of the last decade have had a positive impact on sleep disturbances in HD patients: 694 patients (384 males, 310 females) were surveyed using a specific questionnaire; their clinical, lifestyle

Massimo Sabbatini; Bruno Minale; Anna Crispo; Antonio Pisani; Annalisa Ragosta; Raffaela Esposito; Antonio Cesaro; Bruno Cianciaruso; Vittorio E. Andreucci

2002-01-01

295

Turning patients over in bed  

MedlinePLUS

... arm across the chest. Cross the patient's upper ankle over the bottom ankle. If you are turning the patient onto the ... Make sure the patient's ankles, knees, and elbows are not resting on top of each other. Make sure the head and neck are in line ...

296

Group Interventions with Cancer Patients  

Microsoft Academic Search

Cancer support groups have become increasingly available to patients over the last two decades. Although the various patient groups differ in their philosophy, membership, and aims, the majority can be categorized as predominantly “supportive” or “psychoeduca-tional” in their approach. To date, there is little evidence regarding the relative benefits of the two types of group in improving patients' psychological outcomes.

Sarah Edelman; Ashley Craig; Antony D. Kidman

2000-01-01

297

The Dizzy Elderly Patient  

PubMed Central

Dizziness is a common complaint in elderly people. For those elderly persons whose dizziness reflects true vertigo, the history, physical examination, investigations and underlying diseases are quite similar to those seen in members of younger age groups. However, non-specific dizziness, light-headedness or disequilibrium are much different in the elderly. Rarely is there a single specific cause for the symptom. Rather, it is the end result of an accumulation of factors, physiological and pathological. Successful amelioration requires careful assessment of the patient's entire medical condition, with appropriate treatment. The most important factors are the drug history and therapeutic drug withdrawal. PMID:20469456

Ruth, J.; Goldlist, B.

1986-01-01

298

Bibliotherapy in a Patients' Library *  

PubMed Central

This paper describes the involvement of patients in the Patients' Library at McLean Hospital, and the relationship between them and the librarian in library activities. The publication of a patients' magazine is discussed, with case histories of persons who had taken part in its production. The Patients' Librarian has a personal role in patient therapy, and accounts are given of various activities such as play-reading, poetry-reading, and the discussion of poems by established writers, with therapeutic aims in view. Actual clinical experiences are given. PMID:5146769

McDowell, David J.

1971-01-01

299

[Neurological complications in cancer patients].  

PubMed

Neurological symptoms in cancer patients have a great impact on quality of life and need an interdisciplinary approach. They lead to significant impairment in activities of daily living (gait disorders, dizziness), a loss of patients independency (vegetative disturbances, wheel-chair dependency) and interfere with social activities (ban of driving in case of epilepsy). In this article we describe three main and serious neurological problems in the context of oncological patients. These are chemotherapy-induced polyneuropathy, malignant spinal cord compression and epileptic seizures. Our aim is to increase the awareness of neurological complications in cancer patients to improve patients care. PMID:25146945

Hundsberger, Thomas; Roth, Patrick; Roelcke, Ulrich

2014-08-20

300

[The situation of elderly patients].  

PubMed

Elderly and old tumour patients differ very much individually and a broad range of variation is even to be observed in patients of the same age group. But these patients differ from younger patients in many respects: This concerns the process of treatment decision and the expectations of the therapy on the one hand. Relevant differences with regard to younger patients exist also because of the age-related physiological changes and frequent age-typical comorbidities which may increase the toxicity of a therapy and the surgery-associated morbidity and lethality because of a decreased functional reserve capacity. PMID:18545002

Lüttje, Dieter; Maio, Giovanni; Wedding, Ulrich

2008-01-01

301

PATIENT NAME: PATIENT DATE OF BIRTH: PATIENT MEDICAL RECORD # (IF ADDRESSOGRAPH STAMP IS NOT USED)  

E-print Network

PATIENT NAME: PATIENT DATE OF BIRTH: PATIENT MEDICAL RECORD # (IF ADDRESSOGRAPH STAMP IS NOT USED including copies of my medical record of care received at to the following persons at the locations Operative Reports Ã? Other (please specify) Ã? Pathology Reports Ã? Medical Record Abstract (e.g. History

Mootha, Vamsi K.

302

How patients use domiciliary oxygen.  

PubMed Central

Forty-five patients in Southampton who received domiciliary oxygen were visited at home to find out how they used and coped with their oxygen. Generally, the organisation and administration of supplies presented no problems, nearly all the apparatus complied with the drug tariff, and most patients coped well with the equipment. Only two patients were taking oxygen for prescribed periods; the others were taking it when necessary for symptomatic relief. No patient received oxygen for over five hours daily. Most patients thought that they were helped by oxygen, but only four said that it allowed them to increase their level of activity, and the overall benefit seemed slight. This was partly because oxygen was usually limited to one room, so patients used oxygen after rather than during exercise. The amount of oxygen consumed differed widely, ranging from three and a half cylinders a week in three patients to less than one cylinder in six months in 17 patients. The average yearly cost of oxygen per patient ranged from 500 pounds in patients consuming one cylinder or more per week, to 15 pounds in those consuming less than one cylinder in six months. The main cost of domiciliary oxygen is determined by the number of cylinder refills, so patients who use it infrequently are a relatively small drain on resources. PMID:647308

Jones, M M; Harvey, J E; Tattersfield, A E

1978-01-01

303

The 'Patient experience' revolution.  

PubMed

We're arguably at the most pivotal time in our young profession. The ACA has provided EMS an unprecedented opportunity to become a part of the healthcare system, a move that many of us have dreamed about for decades. We need to pay attention to the changing dynamics of the environment in which we operate. The factors that currently impact hospitals, doctors and other healthcare providers will also impact us sooner than we think. Take the time to help shape our future and how we participate in this new healthcare system. It's time to focus on the patient and the patient's experience with our service. Wayne Gretzky said two important things during an interview when he was asked what makes him such a great hockey player. One was, "You miss 100% of the shots you don't take." The other was, "A good hockey player plays where the puck is. A great hockey player plays where the puck is going to be. I skate to where the puck is going to be, not where it has been." Our advice to you is to go ahead, take the shot, get ahead of the other team and focus on improved customer satisfaction sooner rather than later. PMID:24660359

Hooten, Doug; Zavadsky, Matt

2014-02-01

304

Caring for Latino patients.  

PubMed

Latinos comprise nearly 16 percent of the U.S. population, and this proportion is anticipated to increase to 30 percent by 2050. Latinos are a diverse ethnic group that includes many different cultures, races, and nationalities. Barriers to care have resulted in striking disparities in quality of health care for these patients. These barriers include language, lack of insurance, different cultural beliefs, and in some cases, illegal immigration status, mistrust, and illiteracy. The National Standards for Culturally and Linguistically Appropriate Services address these concerns with recommendations for culturally competent care, language services, and organizational support. Latinos have disproportionately higher rates of obesity and diabetes mellitus. Other health problems include stress, neurocysticercosis, and tuberculosis. It is important to explore the use of alternative therapies and belief in traditional folk illnesses, recognizing that health beliefs are dependent on education, socioeconomic status, and degree of acculturation. Many-but not all-folk and herbal treatments can be safely accommodated with conventional therapy. Physicians must be sensitive to Latino cultural values of simpatia (kindness), personalismo (relationship), respeto (respect), and modestia (modesty). The LEARN technique can facilitate cross-cultural interviews. Some cultural barriers may be overcome by using the "teach back" technique to ensure that directions are correctly understood and by creating a welcoming health care environment for Latino patients. PMID:23317025

Juckett, Gregory

2013-01-01

305

[Treatment of patients with osteoarthritis].  

PubMed

The therapeutic management of patients with osteoarthritis aims to decrease pain and inflammation, improve physical function, and to apply safe and effective treatments. A patient-centered approach implies the active participation of the patient in the design of the treatment plan and in timely and informed decision-making at all stages of the disease. The nucleus of treatment is patient education, physical activity and therapeutic exercise, together with weight control in overweight or obese patients. Self-care by the individual and by the family is fundamental in day-to-day patient management. The use of physical therapies, technical aids (walking sticks, etc.) and simple analgesics, opium alkaloids, and antiinflammatory drugs have demonstrated effectiveness in controlling pain, improving physical function and quality of life and their use is clearly indicated in the treatment of osteoarthritis. Conservative surgery and joint replacement is indicated when treatment goals are not achieved in specific patients. PMID:24467960

Vargas Negrín, Francisco; Medina Abellán, María D; Hermosa Hernán, Juan Carlos; de Felipe Medina, Ricardo

2014-01-01

306

Sinusitis: Special Considerations for Aging Patients  

MedlinePLUS

Sinusitis: Special Considerations for Aging Patients Sinusitis: Special Considerations for Aging Patients Patient Health Information News media interested in covering the latest from AAO-HNS/F can ...

307

Patient's rights charter in Iran.  

PubMed

Given the importance of patient's rights in healthcare, special attention has been given to the concept of patient's rights by the Ministry of Health and Medical Education in Iran. Iranian patient's rights charter has been compiled with a novel and comprehensive approach. This charter aims to elucidate rights of recipients of health services as well as observing ethical standards in medicine. This paper presents the Iranian patient's rights charter. Based on a study done from 2007 to 2009, the charter has been finalized through an extensive consultation involving all stakeholders, patients, physicians, nurses, lawyers, patient associations and health policy makers. The developed charter was adopted by the Ministry of Health in December 2009. Iranian patient's rights charter has been formulated in the framework of 5 chapters and 37 articles including vision and an explanatory note. The five chapters concern right to receiving appropriate services, right to access desired and enough information, right to choose and decide freely about receiving healthcare, right to privacy and confidentiality, and finally right to access an efficient system of dealing with complaints which have been explained in 14, 9, 7, 4 and 3 articles, respectively.  The paper concludes that, adopting the patient's rights charter is a valuable measure to meet patient's rights; however, a serious challenge is how to implement and acculturate observing patient's rights in practice in our healthcare system in Iran. PMID:24658982

Parsapoor, Alireza; Bagheri, Alireza; Larijani, Bagher

2014-01-01

308

[Anaesthesia of epileptic patient].  

PubMed

Although surgery of brain tumors and epilepsy are restricted to few specialized centers, anaesthesia for a patient with epilepsy is commonly encountered. Surgical treatments of epilepsy are currently soaring due to the lack of significant progress about effectiveness of antiepileptic drugs (AEDs). Theoretical principles for the anaesthesiologist are quite complex, involving interactions between physiological and pharmacological anaesthesia and AEDs, such as enzyme induction with the first generation molecules mainly (phenytoin, carbamazepin, phenobarbital). The latest generation AEDs (levetiracetam, lamotrigine, gabapentin, oxcarbazepin, vigabatrin, lacosamide...) are better tolerated and induce fewer drug interactions. Practically, the risk of severe perioperative complications is low, provided that the administration of AEDs is kept as close as possible to its usual dosage, and that metabolic disturbances are prevented. The main anaesthetic drugs to avoid are alfentanil, remifentanil and sevoflurane, although their contraindication are only relative, since the clinical benefit might be clear and the doses should remain moderate. PMID:22687533

Engrand, N

2012-06-01

309

H:\\AAAHC\\P&P\\Administration\\PP Patient Rights and Responsibilities.docx Patient Rights Patient Responsibilities  

E-print Network

privacy, safety and security within the health center. 4. Patient disclosures and records are treatedH:\\AAAHC\\P&P\\Administration\\PP Patient Rights and Responsibilities.docx Patient Rights Patient Responsibilities 1. Patients are treated with respect, consideration and dignity. 2. Patients are provided

Sura, Philip

310

RxHope: Patient Assistance Information  

MedlinePLUS

... FAQ Pharma Companies Below is a list current Patient Assistance Programs. Click on the first letter of ... V W X Y Z AbbVie Norvir Kaletra Patient Assistance Program AbbVie Patient Assistance Foundation AbbVie Patient ...

311

Aortoiliac endarterectomy in young patients.  

PubMed

From 1976 to 1981 a total of 304 aortoiliac thromboendarterectomies (TEA) were carried out. Of these, 47 (16%) were performed in young patients: 25 cases were done through a transperitoneal and 22 through a retroperitoneal approach. All retroperitoneal operations were unilateral. All patients were smokers. Twenty-seven patients had incapacitant claudication, 14 had rest pain and 6 had necrotic lesions. Patency rates at four years were 78% for transperitoneal TEA and 79% for retroperitoneal unilateral TEA. These patency rates compared favorably with those obtained using similar techniques in patients over 50 years of age. In this older group, similar 4 year patency rates were 85% and 82%, respectively. The morbidity and mortality of these approaches was analyzed in patients above and below the age of 50. Our results support the use of TEA in young patients with symptomatic advanced atherosclerosis and question the wisdom of limiting the use of TEA to localized segmental lesions of the aortoiliac segment. PMID:3504686

Capdevila, J M; Marco-Luque, M A; Cairols, M A; Rancaño, J; Simeon, J M

1986-05-01

312

Developing a patient safety plan.  

PubMed

Many healthcare organizations are focused on the development of a strategic plan to enhance patient safety. The challenge is creating a plan that focuses on patient safety outcomes, integrating the multitude of internal and external drivers of patient safety, aligning improvement initiatives to create synergy and providing a framework for meaningful measurement of intermediate and long-term results while remaining consistent with an organizational mission, vision and strategic goals. This strategy-focused approach recognizes that patient safety initiatives completed in isolation will not provide consistent progress toward a goal, and that a balanced approach is required that includes the development and systematic execution of bundles of related initiatives. This article outlines the process used by Hamilton Health Sciences in adopting Kaplan and Norton's strategy map methodology underpinned by their balanced scorecard framework to create a comprehensive multi-year plan for patient safety that integrates best practice literature from patient safety, quality and organizational development. PMID:18382157

Zimmerman, Rosanne; Ip, Ivan; Christoffersen, Emily; Shaver, Jill

2008-01-01

313

A Porsche for patient accrual.  

PubMed

A $1,000 lottery ticket for a Porsche Boxster automobile was offered to the investigator who accrued the most patients to a Southwest Oncology Group prostate cancer protocol. This was done with the admirable intention of increasing patient accrual and improving the outlook for men with high risk prostate cancer. However, the offer of this prize also makes the statement that it is permissible to reward a doctor with an expensive automobile for putting patients on an oncology research protocol. Awarding an expensive prize for patient accrual risks eroding public confidence by creating the perception that clinical investigators, swayed by the allure of an expensive automobile, were motivated by material self-interest rather than the welfare of their patients and the advancement of medical science. I suspect that if the practice of expensive rewards for patient accrual became widespread the cumulative damage would ultimately outweigh the benefits. PMID:16377593

Steinberg, David

2005-01-01

314

Bedside nursing handover: patients' opinions.  

PubMed

Within the context of contemporary nursing practice, bedside handover has been advocated as a potentially more suitable mode for achieving patient-centred care. Given that patients can play an important role in the process, better understanding of patients' perspectives of bedside handover could be a critical determinate for successful implementation of the practice. Using a phenomenological approach, this study attempted to explore patients' perceptions of bedside nursing handover. Four key themes emerged from the patient interviews: 'a more effective and personalised approach', 'being empowered and contributing to error minimization', 'privacy, confidentiality and sensitive topics', and 'training need and avoidance of using technical jargon'. Patients welcome bedside handover as they can be empowered through participation in the process. Nevertheless, attention is needed to ensure that adequate training is provided to nurses and to minimize the use of technical jargon so that handover is delivered with a professional and consistent approach. PMID:25289733

Lu, Sai; Kerr, Debra; McKinlay, Louise

2014-10-01

315

Patient preferences for novel therapy  

Microsoft Academic Search

The authors used the N-of-1 clinical trial methodology to obtain insights about a patient’s preference for garlic for the\\u000a management of his hypertension. The 61-year-old man received garlic, 500 mg by mouth three times a day (3 weeks), or identical\\u000a placebo (3 weeks) in three treatment pairs. While the patient was taking garlic the mean systolic blood pressure decreased\\u000a by

Carlos Alberto Estrada; Mark John Young

1993-01-01

316

Diarrhea in patients with AIDS  

Microsoft Academic Search

Opinion statement  Diarrhea in patients with AIDS is a worldwide problem that can have a devastating impact on quality of life for the patient.\\u000a Chronic diarrhea, usually defined as at least 4 weeks’ duration, is more common in patients with low CD4-positive T-lymphocyte\\u000a counts, signaling advanced immunosuppression. Some organisms, such as Microsporidia, usually cause diarrhea only in the immunosuppressed;\\u000a others, such

Susan C. Morpeth; Nathan M. Thielman

2006-01-01

317

Patient Understanding of Food Labels  

Microsoft Academic Search

Results: Most patients (89%) reported using food labels. While 75% of patients reported at least a high school education and 77% had 9th-grade literacy skills, only 37% had 9th-grade math skills. On average, patients answered 69% (standard deviation, 21%) of the food-label questions correctly. Common reasons for incorrect responses included misapplication of the serving size, confusion due to extraneous material

Russell L. Rothman; Ryan Housam; Hilary Weiss; Dianne Davis; Rebecca Gregory; Tebeb Gebretsadik; Ayumi Shintani; Tom A. Elasy

2006-01-01

318

Depressive Disorders in Stroke Patients  

Microsoft Academic Search

Post-stroke depression is a serious complication of ischemic stroke which has negative influences on patients’ quality of\\u000a life and on recovery from symptoms and the prognosis of the underlying disease. We report here a study of the efficacy of\\u000a treatment of patients with post-stroke depression with Opra, showing improvements in status in 93.3% of patients. Along with\\u000a its antidepressant action,

E. I. Gusev; A. N. Bogolepova

2009-01-01

319

Violent psychiatric patients: a study.  

PubMed

In a study of fifty-three violent psychiatric patients in a psychiatric hospital setting, it was found that there are two distinct major groups of violent patients--one of patients with a long history of antisocial behavior who are often chronically homicidal and suicidal, and another of patients who neither have a history of destructive behavior nor exhibit homicidal or suicidal tendencies. The latter become acutely assaultive only during the course of psychiatric illness. The personality traits and background associated with these two groups offer additional contrasts. Each group presents different problems and, of major importance to the psychiatric practioner, each group requires different management. PMID:7258418

Kermani, E J

1981-04-01

320

Mortality in heart failure patients.  

PubMed

Heart failure (HF) is a clinical syndrome, which is becoming a major public health problem in recent decades, due to its increasing prevalence, especially in the developed countries, mostly due to prolonged lifespan of the general population as well as the increased of HF patients. The HF treatment, particularly, new pharmacological and non-pharmacological agents, has markedly improved clinical outcomes of patients with HF including increased life expectancy and improved quality of life. However, despite the facts that mortality in HF patients has decreased, it still remains unacceptably high. This review of summarizes the evidence to date about the mortality of HF patients. Despite the impressive achievements in the pharmacological and non-pharmacological treatment of HF patients which has undeniably improved the survival of these patients, the mortality still remains high particularly among elderly, male and African-American patients. Patients with HF and reduced ejection fraction have higher mortality rates, most commonly due to cardiovascular causes, compared with patients HF and preserved ejection fraction. PMID:25550250

Bytyçi, Ibadete; Bajraktari, Gani

2015-01-01

321

Working with the Difficult Patient  

PubMed Central

Patients who evoke emotional reactions in the family physician tend to be labelled “difficult”. The difficult patient might be one who “yes . . . but” 's every suggestion, or who demands that the physician provide something inappropriate, like drugs or an unjustifiable letter. Whenever such an interaction occurs, the family physician can expect aggravation, frustration and, often, anger, and the results are likely to be unsatisfactory for both doctor and patient. This article describes an approach which will help the doctor to decide what actually to say or do in response to a difficult patient, especially within the time frame of the short office visit. PMID:21267295

Herbert, Carol P.; Grams, Garry D.

1986-01-01

322

Psychological issues in patient outcomes.  

PubMed

This article provides an overview of the psychological issues of facial plastic surgery patients. It begins with a review of the research on the preoperative psychological characteristics of cosmetic surgery patients. Results from the studies assessing postoperative changes in psychological status are reviewed. The psychological issues of specific patient groups, including adolescents and male patients, are discussed. Individuals who undergo plastic surgical procedures as a result of craniofacial anomalies or facial injuries often face a myriad of psychosocial challenges. These issues are outlined in brief. The article concludes with a discussion of two psychiatric conditions, body dysmorphic disorder and posttraumatic stress disorder, that may be frequently encountered by facial plastic surgeons. PMID:12063660

Sarwer, David B; Crerand, Canice E

2002-05-01

323

AKI in an HIV Patient  

PubMed Central

The renal manifestations of patients infected with HIV are diverse. Patients may have podocytopathies ranging from a minimal-change–type lesions to FSGS or collapsing glomerulopathy. Furthermore, such patients produce a variety of autoantibodies without clinical signs of the disease. Antiretroviral drugs also cause renal injury, including crystals and tubular injury, acute interstitial nephritis, or mitochondrial toxicity. In these circumstances, it is essential to perform a renal biopsy for diagnosis and to guide treatment. Here we describe a patient with HIV who presented with AKI and hematuria without concomitant systemic manifestations. Renal biopsy elucidated the cause of acute deterioration of kidney function. PMID:23559580

Hartle, P. Matthew; Carlo, Mariu E.; Dwyer, Jamie P.

2013-01-01

324

Ethical Aspects of Evaluating a Patient’s Mental Capacity  

PubMed Central

When a patient’s mental capacity to make decisions is open to question, the physician often calls in a psychiatrist to help make the determination. The psychiatrist’s conclusions may be taken to a court to determine the patient’s legal competency. In this article, the author presents several clinical criteria psychiatrists may use when determining patients’ mental capacities. The author discusses two critical ethical questions psychiatrists should consider when they use this criteria: (1) whether they should use a fixed or sliding standard and (2) if they adopt a sliding standard, what clinical factors should be given the greatest weight. The author also discusses whether psychiatrists should take initiative to obtain a second opinion from another psychiatrist or mental health professional. Finally, the author discusses research regarding patients who are likely to have more impaired capacity for performing executive functions, patients requesting surgical procedures that are ethically without precedent, and patients possibly having inner awareness under conditions that previously were not considered possible. PMID:19724765

2009-01-01

325

Patient Education Leads to Better Care for Heart Patients.  

ERIC Educational Resources Information Center

The staff of a heart and circulatory disease program of a State department of health conducted a special project at a city hospital which showed that a well-organized treatment and education program for patients with congestive heart failure increased the patient's knowledge of his disease, medication, and diet as well as his adherence to a…

Rosenberg, Stanley G.

326

Medical Cannabis Patients: Patient Profiles and Health Care Utilization Patterns  

Microsoft Academic Search

The possible medicinal uses of cannabis are growing, yet research on how patients use medical cannabis facility services remains scarce. This article reports on the Cannabis Care Study, in which 130 medical cannabis patients at seven facilities in the San Francisco Bay Area were surveyed to gather information about demographics, personal health practices, health outcomes, service use, and satisfaction with

Amanda Reiman

2007-01-01

327

Triaging patients at risk of influenza using a patient portal  

PubMed Central

Vanderbilt University has a widely adopted patient portal, MyHealthAtVanderbilt, which provides an infrastructure to deliver information that can empower patient decision making and enhance personalized healthcare. An interdisciplinary team has developed Flu Tool, a decision-support application targeted to patients with influenza-like illness and designed to be integrated into a patient portal. Flu Tool enables patients to make informed decisions about the level of care they require and guides them to seek timely treatment as appropriate. A pilot version of Flu Tool was deployed for a 9-week period during the 2010–2011 influenza season. During this time, Flu Tool was accessed 4040 times, and 1017 individual patients seen in the institution were diagnosed as having influenza. This early experience with Flu Tool suggests that healthcare consumers are willing to use patient-targeted decision support. The design, implementation, and lessons learned from the pilot release of Flu Tool are described as guidance for institutions implementing decision support through a patient portal infrastructure. PMID:22140208

Daniels, Titus L; Talbot, Thomas R; McClain, Taylor; Hennes, Robert; Stenner, Shane; Muse, Sue; Jirjis, Jim; Purcell Jackson, Gretchen

2011-01-01

328

Disciplined care for disciplined patients: experience of hospitalized blind patients.  

PubMed

Blindness is a permanent condition that alters daily life of blind people. Interpretive phenomenology was used to understand lived experiences of the hospitalized blind people. "Disciplined care for disciplined patients" was one of the themes that emerged from the data. Provision of disciplined care can help health care professionals provide a holistic and comprehensive competent care for blind patients. PMID:24121699

Shamshiri, Mahmood; Mohammadi, Nooredin; Cheraghi, Mohammad Ali; Vehviläinen-Julkunen, Katri; Sadeghi, Tahereh

2013-01-01

329

Cultural competence: reflections on patient autonomy and patient good.  

PubMed

Terms such as 'cultural competence' and 'transcultural nursing' have comfortably taken their place in the lexicon of health care. Their high profile is a reflection of the diversity of western societies and health care's commitment to provide care that is responsive to the values and beliefs of all who require treatment. However, the relationship between cultural competence and familiar ethical concepts such as patient autonomy has been an uneasy one. This article explores the moral foundations of cultural competence, ultimately locating them in patient autonomy and patient good. The discussion of patient good raises questions about the moral relevance of a value's rootedness in a particular culture. I argue that the moral justification for honoring cultural values has more to do with the fact that patients are strongly committed to them than it does with their cultural rootedness. Finally, I suggest an organizational approach to cultural competence that emphasizes overall organizational preparedness. PMID:21788290

Leever, Martin G

2011-07-01

330

What Do Patients Want? Patient Preference in Wound Care  

PubMed Central

Patient preferences are statements made or actions taken by consumers that reflect their desirability of a range of health options. The concept occupies an increasingly prominent place at the center of healthcare reform, and is connected to all aspects of healthcare, including discovery, research, delivery, outcome, and payment. Patient preference research has focused on shared decisions, decisional aids, and clinical practice guideline development, with limited study in acute and chronic wound care populations. The wound care community has focused primarily on patient focused symptoms and quality of life measurement. With increasing recognition of wound care as a medical specialty and as a public health concern that consumes extensive resources, attention to the preferences of end-users with wounds is necessary. This article will provide an overview of related patient-centered concepts and begin to establish a framework for consideration of patient preference in wound care. PMID:25126474

Corbett, Lisa Q.; Ennis, William J.

2014-01-01

331

Vancomycin Dosing in Neutropenic Patients  

PubMed Central

Background To compare vancomycin pharmacokinetic parameters in patients with and without neutropenia. Methods Patients ?18 years admitted on general wards were included. Routinely vancomycin trough and peak plasma concentrations were measured with a fluorescence polarization immunoassay. Pharmacokinetic parameters of individual patients were determined with maximum a posterior Bayesian estimation (MW Pharm 3.60). Neutropenia was defined as neutrophils <0.5×109 cells/L. Principal Findings A total of 171 patients were included. Patients with neutropenia (n?=?56) had higher clearance of vancomycin (CLva), 67 (±26) mL/min, compared to patients without neutropenia (n?=?115), CLva 50 (±22) mL/min (p<0.001). No significant difference was found in serum creatinine and vancomycin volume of distribution. Neutropenia was positively associated with CLva, independently of relevant co-variables (B: 12.122, 95%CI: 1.095 to 23.149, p?=?0.031). On average patients with neutropenia needed 33% higher doses of vancomycin to attain adequate exposure, i.e. AUC24?400 mg×h/L. Furthermore, 15 initially neutropenic patients in our study group received vancomycin for a second administration period. Ten patients received the second administration period during another neutropenic period and 5 patients during a non-neutropenic phase. All 5 patients with vancomycin during both neutropenic and non-neutropenic phase had higher CLva (91 (±26) mL/min) during the neutropenic period and lower CLva (45 (±10) mL/min) during the non-neutropenic phase (p?=?0.009). Conclusion This study shows that most patients with neutropenia have augmented CLva. In a small group of patients that received vancomycin during two episodes, the augmented CLva seems to be reversible in the non-neutropenic period. Our data indicate that it is important to increase the daily dose with one third in patients with neutropenia (from 15 mg/kg twice daily to 13 mg/kg three times daily). Frequent performance of therapeutic drug monitoring in patients with neutropenia may prevent both therapy failure due to low AUCs and overcomes toxicity due to high vancomycin trough concentrations during recovery from neutropenia. PMID:25390637

Haeseker, Michiel B.; Croes, Sander; Neef, Cees; Bruggeman, Cathrien A.; Stolk, Leo M. L.; Verbon, Annelies

2014-01-01

332

Elderly patients also have rights  

PubMed Central

Background Sharing information with relatives of elderly patients in primary care and in hospital has to fit into the complex set of obligations, justifications and pressures concerning the provision of information, and the results of some studies point to the need for further empirical studies exploring issues of patient autonomy, privacy and informed consent in the day?to?day care of older people. Objectives To know the frequency with which “capable” patients over 65?years of age receive information when admitted to hospital, the information offered to the families concerned, the person who gives consent for medical intervention, and the degree of satisfaction with the information received and the healthcare provided. Method A descriptive questionnaire given to 200 patients and 200 relatives during the patients' stay in hospital. Results Only 5% of patients confirmed that they had been asked whether information could be given to their relatives. A significantly higher proportion of relatives received information on the successive stages of the care offered than did patients themselves. As the age of the patients increased, so the number who were given information, understood the information and were asked for their consent for complementary tests decreased. The degree of satisfaction with the information offered was high for both patients and relatives (86.5% and 84%, respectively), despite the irregularities observed. Conclusions The capacity of elderly patients to participate in the decision?making process is frequently doubted simply because they have reached a certain age and it is thought that relatives should act as their representatives. In Spain, the opinion of the family and doctors appears to play a larger role in making decisions than does the concept of patient autonomy. PMID:18055902

Pérez?Cárceles, M D; Lorenzo, M D; Luna, A; Osuna, E

2007-01-01

333

National survey of hospital patients.  

PubMed Central

OBJECTIVE--To survey patients' opinions of their experiences in hospital in order to produce data that can help managers and doctors to identify and solve problems. DESIGN--Random sample of 36 NHS hospitals, stratified by size of hospital (number of beds), area (north, midlands, south east, south west), and type of hospital (teaching or non-teaching, trust or directly managed). From each hospital a random sample of, on average, 143 patients was interviewed at home or the place of discharge two to four weeks after discharge by means of a structured questionnaire about their treatment in hospital. SUBJECTS--5150 randomly chosen NHS patients recently discharged from acute hospitals in England. Subjects had been patients on medical and surgical wards apart from paediatric, maternity, psychiatric, and geriatric wards. MAIN OUTCOME MEASURES--Patients' responses to direct questions about preadmission procedures, admission, communication with staff, physical care, tests and operations, help from staff, pain management, and discharge planning. Patients' responses to general questions about their degree of satisfaction in hospitals. RESULTS--Problems were reported by patients, particularly with regard to communication with staff (56% (2824/5020) had not been given written or printed information); pain management (33% (1042/3162) of those suffering pain were in pain all or most of the time); and discharge planning (70% (3599/5124) had not been told about warning signs and 62% (3177/5119) had not been told when to resume normal activities). Hospitals failed to reach the standards of the Patient's Charter--for example, in explaining the treatment proposed and giving patients the option of not taking part in student training. Answers to questions about patient satisfaction were, however, highly positive but of little use to managers. CONCLUSIONS--This survey has highlighted several problems with treatment in NHS hospitals. Asking patients direct questions about what happened rather than how satisfied they were with treatment can elucidate the problems that exist and so enable them to be solved. PMID:7819893

Bruster, S.; Jarman, B.; Bosanquet, N.; Weston, D.; Erens, R.; Delbanco, T. L.

1994-01-01

334

Patients as partners, patients as problem-solvers.  

PubMed

This article reports our ongoing work in developing a model of health care communication called collaborative interpretation, which we define as a rhetorical practice that generates building blocks for a more complete and coherent diagnostic story and for a collaborative treatment plan. It does this by situating patients as problem-solvers. Our study begins with an analysis of provider-patient interactions in a specific setting-the emergency department (ED) of an urban trauma-level hospital- where we observed patients and providers miscommunicating in at least 3 distinct areas: over the meaning of key terms, in the framing of the immediate problem, and over the perceived role of the ED in serving the individual and the community. From our observations, we argue that all of these miscommunications and missed opportunities are rooted in mismatched expectations on the part of both provider and patient and the lack of explicit comparison and negotiation of expectations-in other words, a failure to see the patient-provider interaction as a rhetorical, knowledge-building event. In the process of observing interactions, conversing with patients and providers, and working with a team of providers and patients, we have developed an operational model of communication that could narrow the gap between the lay public and the medical profession-a gap that is especially critical in intercultural settings like the one we have studied. This model of collaborative interpretation (CI) provides strategies to help patients to represent their medical problems in the context of their life experiences and to share the logic behind their health care decisions. In addition, CI helps both patient and provider identify their goals and expectations in treatment, the obstacles that each party perceives, and the available options. It is adaptableto various settings, including short, structured conversations in the emergency room, extended dialogue between a health educator and a patient in a clinical setting, and group discussions in support groups, community groups, or health education classrooms. PMID:11853210

Young, Amanda; Flower, Linda

2002-01-01

335

Patient Perspectives on Spirituality and the Patient-physician Relationship  

PubMed Central

OBJECTIVE To identify the preferences and concerns of seriously ill patients about discussing religious and spiritual beliefs with physicians. DESIGN Three focus group discussions with patients who had experienced a recent life-threatening illness. Discussions were audiotaped, transcribed verbatim, and reviewed independently by two investigators to identify discrete comments for grouping into domains. A third investigator adjudicated differences in opinion. Comments were then independently reviewed for relevance and consistency by a health services researcher and a pastoral counselor. SETTING Academic medical center. PARTICIPANTS Referred sample of 22 patients hospitalized with a recent life-threatening illness. MEASUREMENTS AND MAIN RESULTS Almost all of the 562 comments could be grouped into one of five broad domains: 1) religiosity/spirituality, 2) prayer, 3) patient-physician relationship, 4) religious/spiritual conversations, and 5) recommendations to physicians. God, prayer, and spiritual beliefs were often mentioned as sources of comfort, support, and healing. All participants stressed the importance of physician empathy. Willingness to participate in spiritual discussions with doctors was closely tied to the patient-physician relationship. Although divided on the proper context, patients agreed that physicians must have strong interpersonal skills for discussions to be fruitful. Physician-initiated conversation without a strong patient-physician relationship was viewed as inappropriate and as implying a poor prognosis. CONCLUSION Religion and spirituality are a source of comfort for many patients. Although not necessarily expecting physicians to discuss spirituality, patients want physicians to ask about coping and support mechanisms. This exploratory study suggests that if patients then disclose the importance of spiritual beliefs in their lives, they would like physicians to respect these values. PMID:11679036

Hebert, Randy S; Jenckes, Mollie W; Ford, Daniel E; O'Connor, Debra R; Cooper, Lisa A

2001-01-01

336

Gustometry of diabetes mellitus patients and obese patients.  

PubMed

The sensation of adequate taste detection can be associated with satisfaction of food intake. The impairment of taste detection may be associated with the development of obesity. Taste detection is determined hereditarily, but it can be influenced also by the occurrence of neuropathy. To find an explanation for these phenomena, we investigated 73 patients with diabetes mellitus (DM) 2 (i.e., non-insulin-dependent DM); 11 patients with DM 1 (i.e., insulin-dependent DM); 12 obese patients (body-mass index >30) without DM; and 29 control patients. All subjects underwent electrogustometric examination with Hortmman's electrogustometer. During this examination, we obtained electrical thresholds of taste by stimulating appropriate parts of the tongue. We stimulated the apex, middle, and near tongue radix areas on both sides. The resulting value is the average on the left and right sides of the mentioned areas. We considered a value of less than 40 microA to be normal. Values in excess of 100 microA are considered as hypogeusia. Values between 40 and 100 microA are taken as borderline, and ageusia is in excess of 500 microA. According to these criteria, in the DM 2 group, we found 40% of patients with hypogeusia, whereas in the DM 1 group, we found 33% of patients; 25% of patients were in the obese group. Among normal subjects (people without obesity or DM), no hypogeusia was found. We found ageusia in 5% of patients with DM 2, in 3% of patients with DM 1, and in 14% of obese patients. Among normal subjects, we found no ageusia. These results support the hypothesis that diminished taste detection can evoke hyperphagia and later obesity. PMID:10753433

Stolbová, K; Hahn, A; Benes, B; Andel, M; Treslová, L

1999-01-01

337

gastroschisis patients improve outcome?  

E-print Network

OBJECTIVES: Newborns who undergo surgery for gastroschisis correction may present with oliguria, anasarca, prolonged postoperative ileus, and infection. New postoperative therapeutic procedures were tested with the objective of improving postoperative outcome. PATIENTS AND METHODS: One hundred thirty-six newborns participated in one of two phases. Newborns in the first phase received infusions of large volumes of crystalloid solution and integral enteral formula, and newborns in the second phase received crystalloid solutions in smaller volumes, with albumin solution infusion when necessary and the late introduction of a semi-elemental diet. The studied variables were serum sodium and albumin levels, the need for albumin solution expansion, the occurrence of anasarca, the length of time on parenteral nutrition, the length of time before initiating an enteral diet and reaching a full enteral diet, orotracheal intubation time, length of hospitalization, and survival rates. RESULTS: Serum sodium levels were higher in newborns in the second phase. There was a correlation between low serum sodium levels and orotracheal intubation time; additionally, low serum albumin levels correlated with the length of time before the initiation of an oral diet and the time until a full enteral diet was reached. However, the discharge weights of newborns in the second phase were higher than in the first phase. The other studied variables, including survival rates (83.4 % and 92.0%, respectively), were similar for both phases.

Ana Cristina; A. Tannuri; I Luanna; M. Silva; I Antonio; José G. Leal; I Augusto; César F. Moraes; Ii Uenis; Tannuri I

338

JAMA Patient Page: General Anesthesia  

MedlinePLUS

Mechanical ventilator Carbon dioxide absorber Patient monitors Breathing tubes Anesthetic agent vaporizers A N E S T H E S I O L O G Y The ... during emergency surgery if the patient is in shock, during open heart surgery with the heart bypass ...

339

IU Health Physicians Patient Education  

E-print Network

to a more "informed' informed consent. Improved Outcomes: Informed patients are more likely to be compliant with self-care Patients who are better educated are more likely to be medication compliant, adhere better Intervention Control 3 out of 3 12% 0% 2 out of 3 42% 23% 1 out of 3 33% 46% 0 out of 3 13% 31% #12;

Zhou, Yaoqi

340

Nurse Burnout and Patient Satisfaction  

Microsoft Academic Search

Background: Amid a national nurse shortage, there is growing concern that high levels of nurse burnout could adversely affect patient outcomes. Objectives: This study examines the effect of the nurse work environment on nurse burnout, and the effects of the nurse work environment and nurse burnout on patients' satisfaction with their nursing care. Research Design\\/Subjects: We conducted cross-sectional surveys of

Doris C. Vahey; Linda H. Aiken; Douglas M. Sloane; Sean P. Clarke; Delfino Vargas

2004-01-01

341

Patient Guide to Cardiac Surgery  

E-print Network

Patient Guide to Cardiac Surgery at the Massachusetts General Hospital #12;Contents Welcome 1 Your cover #12;Welcome to the MGH Cardiac Surgical Service The cardiac surgical team at the Massachusetts General Hospital is committed to giving you the best medical care. As a patient, you are a part of our

Mootha, Vamsi K.

342

Nutrition in elderly hemodialysis patients  

Microsoft Academic Search

The elderly dialysis population is increasing. Current nutritional recommendations for this group of patients are based on extrapolations of the recommendations for the general well elderly and adult hemodialysis populations. More than 60% of patients receiving renal replacement therapy in the US will be over the age of 65 by the year 2000. This mandates the need for the development

Jerrilynn D. Burrowes; Sharon H. Stall

1995-01-01

343

Pharmacotherapeutics for the AIDS Patient.  

ERIC Educational Resources Information Center

Anticipated shifts in the demographics of the Acquired Immune Deficiency Syndrome (AIDS) epidemic are examined, current state-of-the-art AIDS patient management is summarized, and some unique facets of drug therapy in the AIDS patient are discussed, including adverse reactions, complex drug interactions, use of investigational drugs, and…

Fife, Kenneth H.

1991-01-01

344

Garlic, hypertension and patient education  

Microsoft Academic Search

The aims of this study are to investigate the frequency of garlic usage in hypertensive population and to evaluate acute effect of garlic and garlic tablets on blood pressure in patients with hypertension. 4102 of the 7703 patients (53.3%) reported that they were using garlic. No significant effect on blood pressure was observed in any of the three groups (placebo,

Mustafa Capraz; Melda Dilek; Tekin Akpolat

2007-01-01

345

Oversedation in a pediatric patient  

Microsoft Academic Search

Management of uncooperative pediatric dental patients may be carried out successfully by employing a variety of pharmacologic agents and techniques. Any method selected has associated risks even when calculated doses and accepted proto- col are followed carefully. Early recognition of an undesirable response and prompt, appropriate reaction to that response is essential in order to avoid harm to the patient.

C. Richard Bennett

1987-01-01

346

Patient Disclosure of Medical Misdeeds  

ERIC Educational Resources Information Center

Modern patients walk a tightrope between respecting medical authority and acting as knowledgeable advocates regarding health issues, with the agency and responsibilities that come with this. This article uses conversation analysis to explore this balance in relation to patient disclosures of medical misdeeds in video-recorded primary care medical…

Bergen, Clara; Stivers, Tanya

2013-01-01

347

Dental Surgery in Anticoagulated Patients  

Microsoft Academic Search

ontinuous oral anticoagulant therapy has been used to decrease the risk of thrombo- embolism for more than half a century, prolonging the lives of thousands of patients. Many physicians recommend interrupting continuous anticoagulant therapy for den- tal surgery to prevent hemorrhage. In reviewing the available literature, there are no well-documented cases of serious bleeding problems from dental surgery in patients

Michael J. Wahl

1998-01-01

348

Hallux Ulceration in Diabetic Patients  

Microsoft Academic Search

We undertook a prospective cohort study to assess risk factors associated with hallux ulceration, and to determine the incidence of healing or amputation, in consecutive patients with diabetes mellitus who were treated over the observation period extending from September 2004 to March 2005, at the Jabir Abu Eliz Diabetic Centre, Khartoum City, Sudan. There were 122 diabetic patients in the

Mohamed ElMakki Ahmed; Abdulhakim O. Tamimi; Seif I. Mahadi; AbuBakr H. Widatalla; Mohamed A. Shawer

2010-01-01

349

The Coronary Patient in Industry  

NASA Technical Reports Server (NTRS)

The coronary patient, as he pertains to industry particularly NASA, is discussed. Concepts of precoronary care, acute attacks which may develop while on the job, and the return of the cardiac patient to work are covered. Major emphasis was on the prevention of sudden death due to coronary disease.

Schuster, B.

1971-01-01

350

Liver fibrosis in overweight patients  

Microsoft Academic Search

Background & Aims: A common clinical issue is whether overweight patients with abnormal liver function test results should undergo liver biopsy. Although serious liver injury can occur, its prevalence and risk factors are not well known. Methods: Ninety-three consecutive patients with abnormal liver function tests (but without overt liver disease), body mass index (BMI) > 25 kg\\/m2, and no alcoholic,

Vlad Ratziu; Philippe Giral; Frederic Charlotte; Eric Bruckert; Vincent Thibault; Ioannis Theodorou; Lina Khalil; Gérard Turpin; Pierre Opolon; Thierry Poynard

2000-01-01

351

Viscoelastic cushion for patient support  

NASA Technical Reports Server (NTRS)

Flexible container, filled with liquid, provides supportive device which conforms to patient's anatomy. Uniform cushion pressure prevents formation of decubitus ulcers, while the porous sponge substructure damps fluid movement through cushion response so that patient is not dumped when his weight shifts.

Sauers, D. G.

1971-01-01

352

Patient safety: the doctor's perspective.  

PubMed

Medical errors can be defined as the failure of a planned action to be completed as intended or the use of a wrong plan to achieve an aim. Beyond their economic cost and their cost in human lives, errors cause loss of trust in the healthcare system by patients and diminished satisfaction by both patients and health professionals. There are many evidence-based safety-oriented behaviours and interventions that are easily implemented, such as ultrasound-guided central venous catheter insertion, prevention of catheter-related bloodstream infection and more. In vascular access, the development of research in patient safety has raised a variety of issues requiring study in order to provide the optimal patient safety approach. Patients are major contributors to their own safety, and as such, physicians should develop a new approach to involve them in the cycle of decision making through every step of their treatment. There are many opportunities along this path for the patient to be engaged in safety behaviours and for the access team to ensure such behaviours by employing simple strategies. The advent of the access centre, based on multidisciplinary teamwork, has enhanced the potential to improve patient safety by prevention of errors in planning and performing access surgery, avoiding delay in treatment of access malfunction and improving communication between the team members. However, a significant effort in research is still needed in order to implement intervention by evidence-based data focused on patient safety. PMID:25751565

Shemesh, David; Olsha, Oded; Goldin, Ilya; Danin, Sigalit

2015-03-01

353

Ileorectal Anastomosis: Appreciation by Patients  

PubMed Central

Two hundred patients treated by ileorectal anastomosis for ulcerative colitis were questioned about their opinion of the result of their operation. The vast majority of patients led normal business and social lives and their activities had been greatly altered for the better by this operation. PMID:5769863

Jagelman, D. G.; Lewis, C. B.; Rowe-Jones, D. C.

1969-01-01

354

Oocyte cryopreservation in oncological patients.  

PubMed

The use of chemotherapy and radiotherapy in oncological patients may reduce their reproductive potential. Sperm cryopreservation has been already used in men affected by neoplastic disease. Oocyte cryopreservation might be an important solution for these patients at risk of losing ovarian function. A program of oocyte cryopreservation for oncological patients is also present in our center. From June 1996 to January 2000, 18 patients awaiting chemotherapy and radiotherapy for neoplastic disease were included in our oocyte cryopreservation program. Our experience documents that oocyte storage may be a concrete and pragmatic alternative for oncological patients. The duration of oocyte storage does not seem to interfere with oocyte survival as pregnancies occurred even after several years of gamete cryopreservation in liquid nitrogen. PMID:15041124

Porcu, Eleonora; Fabbri, Raffaella; Damiano, Giuseppe; Fratto, Rosita; Giunchi, Susanna; Venturoli, Stefano

2004-04-01

355

Patient counseling for osteoporosis prevention.  

PubMed Central

Counseling techniques and methods are more important parameters than message content for ensuring that a desired change in behavior occurs. Knowledge is necessary but not sufficient for behavior change, and teaching should not be confused with learning. The education of patients with osteoporosis poses two problems: patient involvement in deciding whether to initiate treatments such as estrogen replacement therapy, calcium supplements, and weight-bearing exercises, and assuring that the patient adheres to the prescribed regimen. The physician, while adequately outlining the risks of treatments, should also simplify the explanation to assist patients in making a decision about treatment. Guidelines are provided to aid the clinician in this task. Indicators of potential nonadherence should be evaluated, and obstacles to nonadherence removed by suggesting behavior modifications that will ensure the patient's continuation of the prescribed regimen. PMID:2517708

Bartlett, E E

1989-01-01

356

Electronic reminders to patients within an interactive patient health record.  

PubMed

Keeping patients with complex medical illnesses up to date with their preventive care and chronic disease management services, such as lipid testing and retinal exam in patients with diabetes, is challenging. Within a commercially available electronic health record (EHR) with a secure personal health record (PHR), we developed a system that sends up to three weekly reminders to patients who will soon be due for preventive care services. The reminder messages reside within the secure PHR, which is linked to the EHR, and are displayed on a screen where patients can also send to the physician's office an electronic message to request appointments for the needed services. The reminder messages stop when the patient logs on to review the reminders. The system, designed with patient input, groups together all services that will be due in the next 3 months to avoid repeatedly messaging the patient. After 2 months, the cycle of reminders begins again. This system, which is feasible and economical to build, has the potential to improve care and compliance with quality measures. PMID:23611639

Fischer, Gary S; Hess, Rachel; Landeen, Babette M; Weimer, Melissa; Zieth, Caroline R; Dong, Xinxin; Clark, Sunday; Roberts, Mark S

2013-06-01

357

Display methods of electronic patient record screens: patient privacy concerns.  

PubMed

To provide adequate care, medical professionals have to collect not only medical information but also information that may be related to private aspects of the patient's life. With patients' increasing awareness of information privacy, healthcare providers have to pay attention to the patients' right of privacy. This study aimed to clarify the requirements of the display method of electronic patient record (EPR) screens in consideration of both patients' information privacy concerns and health professionals' information needs. For this purpose, semi-structured group interviews were conducted of 78 medical professionals. They pointed out that partial concealment of information to meet patients' requests for privacy could result in challenges in (1) safety in healthcare, (2) information sharing, (3) collaboration, (4) hospital management, and (5) communication. They believed that EPRs should (1) meet the requirements of the therapeutic process, (2) have restricted access, (3) provide convenient access to necessary information, and (4) facilitate interprofessional collaboration. This study provides direction for the development of display methods that balance the sharing of vital information and protection of patient privacy. PMID:23920803

Niimi, Yukari; Ota, Katsumasa

2013-01-01

358

Promoting better care for stigmatised patients.  

PubMed

This article discusses the role of nurses and nurse leaders in the prevention and resolution of patient stigmatisation. The multiple nurse, patient and environmental factors that contribute to difficulties in nurse-patient interactions are outlined. The antecedents and consequences of patient stigmatisation are discussed and leadership strategies for counteracting and preventing patient stigmatisation are explored. The reader is encouraged to reflect on the role of patient stigmatisation in nursing practice and consider ways to promote better care of stigmatised patients. PMID:25515484

Pottle, Jessica; Marotta, Jill

2014-12-31

359

Helping patients discuss CINV management: development of a Patient Charter  

PubMed Central

In April 2012, an Expert Group of specialist cancer nurses working in a variety of settings (e.g. chemotherapy delivery, chemotherapy service design, research, nurse leadership and patient information/advocacy) participated in telephone/web-based meetings, with the aim of sharing current experience of chemotherapy-induced nausea and vomiting (CINV) management, and reaching a consensus on the development of a Patient Charter, designed to help patients understand CINV management, and setting out key questions they may wish to ask their healthcare professionals. PMID:23593098

Young, Annie; Dielenseger, Pascale; Fernandez Ortega, Paz; Fernandez Perez, Dolores; Jones, Philippa; Lennan, Elaine; O’Donovan, Eileen; Sharp, Sue; Whiteford, Alison; Wiles, Lilian

2013-01-01

360

PATIENT-REPORTED OUTCOMES (PROs): PUTTING THE PATIENT PERSPECTIVE IN PATIENT-CENTERED OUTCOMES RESEARCH  

PubMed Central

Patient-centered outcomes research (PCOR) aims to improve care quality and patient outcomes by providing information that patients, clinicians, and family members need regarding treatment alternatives, and emphasizing patient input to inform the research process. PCOR capitalizes on available data sources and generates new evidence to provide timely and relevant information and can be conducted using prospective data collection, disease registries, electronic medical records, aggregated results from prior research, and administrative claims. Given PCOR’s emphasis on the patient perspective, methods to incorporate patient-reported outcomes (PROs) are critical. PROs are defined by the U.S. Food & Drug Administration as “Any report coming directly from patients… about a health condition and its treatment.” However, PROs have not routinely been collected in a way that facilitates their use in PCOR. Electronic medical records, disease registries, and administrative data have only rarely collected, or been linked to, PROs. Recent technological developments facilitate the electronic collection of PROs and linkage of PRO data, offering new opportunities for putting the patient perspective in PCOR. This paper describes the importance of and methods for using PROs for PCOR. We (1) define PROs; (2) identify how PROs can be used in PCOR, and the critical role of electronic data methods for facilitating the use of PRO data in PCOR; (3) outline the challenges and key unanswered questions that need to be addressed for the routine use of PROs in PCOR; and (4) discuss policy and research interventions to accelerate the integration of PROs with clinical data. PMID:23774513

Snyder, Claire F.; Jensen, Roxanne E.; Segal, Jodi B.; Wu, Albert W.

2013-01-01

361

78 FR 59036 - Patient Safety Organizations: Voluntary Relinquishment From Cogent Patient Safety Organization, Inc.  

Federal Register 2010, 2011, 2012, 2013, 2014

...Agency for Healthcare Research and Quality Patient Safety Organizations: Voluntary Relinquishment From Cogent Patient Safety Organization, Inc. AGENCY: Agency...SUMMARY: The Patient Safety and Quality Improvement Act...

2013-09-25

362

76 FR 7853 - Patient Safety Organizations: Voluntary Delisting From Oregon Patient Safety Commission  

Federal Register 2010, 2011, 2012, 2013, 2014

...Agency for Healthcare Research and Quality Patient Safety Organizations: Voluntary Delisting From Oregon Patient Safety Commission AGENCY: Agency for...SUMMARY: Oregon Patient Safety Commission: AHRQ has...

2011-02-11

363

78 FR 40146 - Patient Safety Organizations: Voluntary Relinquishment From Northern Metropolitan Patient Safety...  

Federal Register 2010, 2011, 2012, 2013, 2014

...for Healthcare Research and Quality Patient Safety Organizations: Voluntary Relinquishment From Northern Metropolitan Patient Safety Institute AGENCY: Agency for...SUMMARY: The Patient Safety and Quality Improvement...

2013-07-03

364

76 FR 58812 - Patient Safety Organizations: Delisting for Cause of Patient Safety Organization One, Inc.  

Federal Register 2010, 2011, 2012, 2013, 2014

...Agency for Healthcare Research and Quality Patient Safety Organizations: Delisting for Cause of Patient Safety Organization One, Inc. AGENCY...SUMMARY: Patient Safety Organization One, Inc.: AHRQ...

2011-09-22

365

Spiritual care in hospitalized patients  

PubMed Central

BACKGROUND: Spiritual needs are among an individual's essential needs in all places and times. With his physical and spiritual dimensions and the mutual effect of these two dimensions, human has spiritual needs as well. These needs are an intrinsic need throughout the life; therefore, they will remain as a major element of holistic nursing care. One of the greatest challenges for nurses is to satisfy the patients’ spiritual needs. METHODS: This is a qualitative study with hermeneutic phenomenological approach. Data were collected from 16 patients hospitalized in internal medicine-surgery wards and 6 nurses in the respective wards. Data were generated by open-ended interview and analyzed using Diekelmann's seven-stage method. Rigorousness of findings was confirmed by use of this method as well as team interpretation, and referring to the text and participants. RESULTS: In final interpretation of the findings, totally 10 sub-themes, three themes including formation of mutual relation with patient, encouraging the patient, and providing the necessary conditions for patient's connection with God, and one constitutive pattern, namely spiritual need of hospitalized patients. CONCLUSIONS: Spiritual needs are those needs whose satisfaction causes the person's spiritual growth and make the person a social, hopeful individual who always thanks God. They include the need for communication with others, communication with God, and being hopeful. In this study, the three obtained themes are the spiritual needs whose satisfaction is possible in nursing system. Considering these spiritual aspects accelerates patient's treatment. PMID:22039390

Yousefi, Hojjatollah; Abedi, Heidar Ali

2011-01-01

366

Celebrity Patients, VIPs, and Potentates  

PubMed Central

Background: During the second half of the 20th century, the literature on the doctor-patient relationship mainly dealt with the management of “difficult” (personality-disordered) patients. Similar problems, however, surround other types of “special” patients. Method: An overview and analysis of the literature were conducted. As a result, such patients can be subcategorized by their main presentations; each requires a specific management strategy. Results: Three types of “special” patients stir up irrational feelings in their caregivers. Sick celebrities threaten to focus public scrutiny on the private world of medical caregivers. VIPs generate awe in caregivers, with loss of the objectivity essential to the practice of scientific medicine. Potentates unearth narcissism in the caregiver-patient relationship, which triggers a struggle between power and shame. Pride, privacy, and the staff's need to be in control are all threatened by introduction of the special patient into medicine's closed culture. Conclusion: The privacy that is owed to sick celebrities should be extended to protect overexposed staff. The awe and loss of medical objectivity that VIPs generate are counteracted by team leadership dedicated to avoiding any deviation from standard clinical procedure. Moreover, the collective ill will surrounding potentates can be neutralized by reassuring them that they are “special”—and by caregivers mending their own vulnerable self-esteem. PMID:15014712

Groves, James E.; Dunderdale, Barbara A.; Stern, Theodore A.

2002-01-01

367

Character traits of malodor patients.  

PubMed

Many patients visit oral malodor clinics because of malodors which are brought to their attention by friends and family, or because they note the behavior of people around them, they suspect a problem and develop a fear of having an oral malodor. However, only around 30% of such patients actually have levels of malodor high enough to bother other people. Many patients exhibit halitophobia symptoms, which present as self-perception of malodor, and thus have a strong obsession about their smell which results in distress. Here, we carried out a study on 300 outpatients who visited the Tokyo Dental College Chiba Hospital Odor Clinic. We used the Tokyo University Egogram (TEG) to elucidate character traits of affected outpatients and compared the occurrence of TEG types in these patients with those of normal individuals. We discovered that 10.4% of patients were A-dominant type, which was 10.6% lower than the 21.0% of normal individuals. On the other hand, 18.4% of patients were N-type (NP high, FC low), which was 9.9% higher than the 8.5% of normal individuals. Results revealed that very few of the malodor outpatients exhibited the trait that shows intelligence, calm judgment, and self-affirmation, and as a result enjoy their life. Instead, many of these patients tended to show high levels of kindness and appeared to be holding themselves back and exercising patience. PMID:21986393

Sugiyama, Toshiko; Kameyama, Atsushi; Yamakura, Daiki; Morinaga, Kazuki; Tsunoda, Masatake

2011-01-01

368

Patient-Physician Web Messaging  

PubMed Central

BACKGROUND Patients want electronic access to providers. Providers fear being overwhelmed by unreimbursed messages. OBJECTIVE Measure the effects of patient-physician web messaging on primary care practices. DESIGN/SETTING Retrospective analysis of 6 case and 9 control internal medicine (IM) and family practice (FP) physicians' message volume, and a survey of 5,971 patients' web messaging with 267 providers and staff in 16 community primary care clinics in the Sacramento, CA region. MEASUREMENTS AND MAIN RESULTS Case telephone volume was 18.2% lower (P =.002) and fell 6.50 times faster than control. Case total telephone plus web message volume was 13.7% lower (P =.025) and fell 5.84 times faster than control. Surveys were responded to by 40.3% (1,743/4,320) of patients and 61.4% (164/267) of providers and staff. Patients were overwhelmingly satisfied and providers and staff were generally satisfied; both found the system easy to use. Patient satisfaction correlated strongly with provider response time (?=0.557), and provider/staff satisfaction with computer skills (?=0.626) (Goodman-Kruskal Gamma [?] measure of ordinal association). CONCLUSIONS Secure web messaging improves on e-mail with encryption, access controls, message templates, customized message and prescription routing, knowledge content, and reimbursement. Further study is needed to determine whether reducing telephone traffic through the use of web messaging decreases provider interruptions and increases clinical efficiency during the workday. Satisfaction with web messaging may increase patient retention. PMID:15693928

Liederman, Eric M; Lee, Jerry C; Baquero, Victor H; Seites, Paul G

2005-01-01

369

Patient Empowerment: Myths and Misconceptions  

PubMed Central

Objective The purpose of this article is to clarify the concept of empowerment and to correct common misconceptions about its use in diabetes care and education. Methods The patient empowerment approach is well suited to helping patients make self-selected changes related to weight, nutrition, and physical activity. Although the concept of patient empowerment has become an integral part of diabetes education, an accurate understanding and authentic application of empowerment has not occurred as readily. The empowerment approach is clarified and common misconceptions have been corrected. Results Embracing empowerment means making a paradigm shift that is often difficult because the traditional approach to care is embedded in the training and socialization of most health care professionals (HCP). Conclusion Unlike the traditional approach, empowerment is not something one does to patients. Rather, empowerment begins when HCPs acknowledge that patient are in control of their daily diabetes care. Empowerment occurs when the HCPs goal is to increase the capacity of patients to think critically and make autonomous, informed decisions. Empowerment also occurs when patients are actually making autonomous, informed decisions about their diabetes self-management. Practice Implications Clarity about all aspects of the empowerment approach is essential if it is to be used effectively. PMID:19682830

Anderson, Robert M.; Funnell, Martha M.

2009-01-01

370

Patients' perspectives on actinic keratosis.  

PubMed

Many factors influence patients' perspectives on actinic keratosis (AK). The wish to keep a sense of control prompts many to seek information, which they then interpret according to their personal perspective. Speculations regarding the risk of getting skin cancer and emotional reactions may be expected due to worries about the worsening of the condition, losing control, and participating in UV-related activities. In their contact with physicians, treatment can be an additional issue. Treatment of AK may cause pain and may in itself result in a perceived diminished quality of life. The Actinic Keratosis Quality of Life questionnaire can be used as a valuable tool to represent the effects of treatment on quality of life and to classify patient subpopulations. Studies have suggested that AK patients are more compliant compared to those with other skin diseases. Still fear of stigmatisation may be present during treatment, which may disturb social life. Social and personal factors are crucial to patients' coping strategies, and financial aspects may have an impact on advisable UV-related behaviours. Some AK patients may benefit from interventions to improve their stress response capacity. The clear causality of AK requires a change in behaviour, which is met by multi-conditioned resistance. The physician should be aware that patients might feign acceptance but justify continued UV exposure to themselves with a variety of arguments. Tanning is of great importance for the self-esteem of many AK patients, and tanning addiction should be considered. PMID:25561200

Esmann, Solveig

2015-01-01

371

Optimal nutrition in hemodialysis patients.  

PubMed

Protein-energy wasting (PEW) is highly prevalent in patients undergoing maintenance hemodialysis (MHD). It is important to note that there is a robust association between the extent of PEW and the risk of hospitalization and death in these patients, regardless of the nutritional marker used. The multiple etiologies of PEW in advanced kidney disease are still being elucidated. Apart from the multiple mechanisms that might lead to PEW, it appears that the common pathway for all of the derangements is related to exaggerated protein degradation along with decreased protein synthesis. The hemodialysis procedure per se is an important contributor to this process. Metabolic and hormonal derangements such as acidosis, inflammation, and resistance to anabolic properties of insulin resistance and growth hormone are all implicated for the development of PEW in MHD patients. Appropriate management of MHD patients at risk for PEW requires a comprehensive combination of strategies to diminish protein and energy depletion and to institute therapies that will avoid further losses. The mainstay of nutritional treatment in MHD patients is provision of an adequate amount of protein and energy, using oral supplementation as needed. Intradialytic parenteral nutrition should be attempted in patients who cannot efficiently use the gastrointestinal tract. Other anabolic strategies such as exercise, anabolic hormones, anti-inflammatory therapies, and appetite stimulants can be considered as complementary therapies in suitable patients. PMID:23439378

Ikizler, T Alp

2013-03-01

372

[Current practise in splenectomised patients].  

PubMed

Asplenia is found in a very heterogeneous group of patients with a wide range of age and comorbidities. These patients have an increased risk of overwhelming post-splenectomy infections (OPSI) even several decades after splenectomy. The mortality rate associated with OPSI is 30 - 60 %, which is why the immunisation against encapsulated bacteria is mandatory. In addition these patients show an increased risk of thrombosis of the portal venous system. In the present article all the necessary, during daily practice often neglected preventive measures and behavioural rules are discussed. PMID:23454566

Goede, Jeroen S; Siciliano, Daniele R

2013-03-01

373

Improving oral hygiene for patients.  

PubMed

Systematic reviews and patient safety initiatives recommend that oral hygiene should be part of routine patient care. However, evidence suggests it is often neglected in hospitals and care homes. Research recommends encouraging beliefs that support oral hygiene, and teaching nurses appropriate skills, as necessary prerequisites to implementing best practice in hospital wards. This article describes a pilot study of an educational workshop on oral hygiene. Results from the pilot study suggest that this workshop is a feasible intervention for a service-wide trial. The literature suggests that other interventions are required to complement this approach if nurses are to make oral hygiene a priority in daily patient care. PMID:25563127

Bonetti, Debbie; Hampson, Victoria; Queen, Kerry; Kirk, Donna; Clarkson, Jan; Young, Linda

2015-01-13

374

[Patients' mailbox and electronic prescription].  

PubMed

Electronic prescribing shall contribute essentially to improved healthcare services from 2006 onwards in Germany. The desired improvements, however, can only be achieved with "real" telematic solutions. The alternative of pharmaceutical prescription transmission via secure network connections or via electronic health card provides a considerable empowerment to the patients. Electronic prescribing, however, does not provide direct advantages to patients. Benefits for them can be realised by a drug documentation system, ready to identify contraindications or multiple prescriptions. The patients' acceptance of the system to be established therefore largely depends on the concurrent introduction of both elements. PMID:16003566

Brill, C-W; Förster, K; Keil, W

2005-07-01

375

Biofeedback training in patients with fecal incontinence  

Microsoft Academic Search

PURPOSE: This study was undertaken to assess the functional results of biofeedback training in patients with fecal incontinence in relation to clinical presentation and anorectal manometry results. METHODS: Twenty-six consecutive patients with fecal incontinence were treated with biofeedback training using anorectal manometry pressure for visual feedback. Ten patients had passive incontinence only, six patients had urge incontinence, and ten patients

Abdulhakim Glia; Meta Gylin; Jan Erik Åkerlund; Ulrik Lindfors; Greger Lindberg

1998-01-01

376

Preoperative Evaluation of Complex Laparoscopic Patients  

Microsoft Academic Search

Complex laparoscopic patients require careful preoperative planning for optimal outcome. These patients present unique problems that necessitate special consideration and a surgeon experienced in basic laparoscopic cases. This chapter discusses a number of such patient groups, including patients with previous abdominal surgery, significant cardiopulmonary comorbidity, obesity, and pregnancy. When evaluating any of these patients, six questions should be asked: 1.

Dmitry Oleynikov; Karen D. Horvath IV

377

A PATIENT GUIDE TO ORTHOPAEDIC TRAUMA  

E-print Network

Proxy 4 Office of Patient Advocacy 4 THE TEAM 5-8 Orthopaedic Trauma Professional Staff 5 The MGHA PATIENT GUIDE TO ORTHOPAEDIC TRAUMA CARE AT MGH expert care for trauma patients Phalanges Carpals HOSPITAL #12;1 INTRODUCTION 3 PATIENT RIGHTS 4-5 Patient Rights and Responsibilities 4 Ethics 4 Health Care

Mootha, Vamsi K.

378

Patient blood management to reduce transfusion need.  

PubMed

Patient blood management is a multidisciplinary, patient-centered approach aimed at improving patient outcomes, preserving the blood supply, and reducing costs. By identifying patients at risk for transfusion and taking steps to maintain hemoglobin concentration, manage anemia, optimize hemostasis, and minimize blood loss, clinicians can improve patient outcomes. PMID:25621967

Lynn, Shannon

2015-02-01

379

[Shockwave lithotripsy in sialolithiasis patients].  

PubMed

Shockwave lithotripsy was performed by various appliances in sialolithiasis patients. The best results were obtained by means of miniature appliances. Lithotripsy proved to be useful safe alternative for sialolithiasis treatment. PMID:24781125

Abdusalamov, M R; Afanas'ev, V V; Gamataev, I I

2014-01-01

380

Medical Technology for Superior Patient  

E-print Network

Trusted Medical Technology for Superior Patient Care Technical Services Partnership ­ Comprehensive healthcare technology management and services Technical Services Partnership (TSP) helps healthcare throughout the life cycle Keeping up with the rapid advances in health care technology is a complex

Hayden, Nancy J.

381

JAMA Patient Page: Chagas Disease  

MedlinePLUS

... of the American Medical Association JAMA PATIENT PAGE Chagas Disease C hagas disease, or American trypanosomiasis, is ... or an organ transplanted from an infected donor. Chagas disease occurs mainly in Latin America, where an ...

382

Processing Requests for Patient Data  

Cancer.gov

This document describes general policies of the NCI funded cancer Cooperative Groups on providing individual patient data to investigators for use in research projects. Each group will have a more detailed set of procedures implementing the general policy.

383

JAMA Patient Page: Panic Disorder  

MedlinePLUS

... of the American Medical Association JAMA PATIENT PAGE Panic Disorder O verwhelming fright, fear, or terror, called panic, ... worry about another panic attack, this is termed panic disorder . Not every person who has a panic attack ...

384

Crohn's disease in black patients.  

PubMed Central

Crohn's disease is less prevalent in blacks than in whites. However, when it does occur, it is associated with a high degree of morbidity and is frequently unrecognized at initial presentation. Forty-three patients with Crohn's disease presented to Howard University Hospital between 1965 and 1987. There were 156 hospital admissions, 47 emergency room visits, and 76 clinic visits over this 22-year period. Twenty-eight patients were female and 15 were male. The age of presentation for males ranged from 18 to 63 years and for females, 12 to 74 years. Crohn's disease should be considered in black patients who present with chronic abdominal pain and diarrhea. With correct diagnosis and appropriate medical therapy, patients should have an enhanced quality of life with less morbidity. Images Figure 1 Figure 2 Figure 3 PMID:2280420

Paul, H.; Barnes, R. W.; Reese, V. E.; Childress, M. H.; Scott, V.; Leffall, L. D.

1990-01-01

385

JAMA Patient Page: Medical Journals  

MedlinePLUS

... other health professionals. With the development of electronic publishing, many medical journals now have Web sites on ... This Patient Page is based on one previously published in the June 5, 2002, issue of JAMA . ...

386

JAMA Patient Page: Achilles Tendinopathy  

MedlinePLUS

... is frequently described in patients’ histories. While not proven, causes may include SYMPTOMS Pain is typically felt ... last resort because recovery is slow. Although not proven, preventive measures often include choosing running shoes that ...

387

CDRP - Patient Navigator Program - Funding  

Cancer.gov

As part of the "Cooperative Planning Grant for Cancer Disparities Research Partnership Program," (CDRP) the National Cancer Institute's Center to Reduce Cancer Health Disparities provided funding for a Patient Navigator Program to be implemented at the funded sites.

388

JAMA Patient Page: Cystic Fibrosis  

MedlinePLUS

... of the American Medical Association JAMA PATIENT PAGE Cystic Fibrosis C ystic fibrosis (CF) is a genetic (inherited) ... of the CF gene, that child will develop cystic fibrosis and can also pass the CF gene on ...

389

JAMA Patient Page: Aortic Aneurysms  

MedlinePLUS

... of the American Medical Association JAMA PATIENT PAGE Aortic Aneurysms T he aorta is the body’s largest artery ... wall that may stretch and bulge outwards. An aortic aneurysm is a stretched and bulging section in the ...

390

JAMA Patient Page: Bone Fractures  

MedlinePLUS

... the American Medical Association JAMA PATIENT PAGE Bone Fractures A bone fracture is a break in a ... below) to treat bone fractures. CAUSES OF BONE FRACTURES FOR MORE INFORMATION • American Academy of Orthopaedic Surgeons ...

391

JAMA Patient Page: Burn Injuries  

MedlinePLUS

... of the American Medical Association JAMA PATIENT PAGE Burn Injuries B urns, most commonly caused by fire, ... burn injuries in the United States. TYPES OF BURNS FOR MORE INFORMATION • World Health Organization www.who. ...

392

JAMA Patient Page: Anal Fissure  

MedlinePLUS

... All rights reserved. JAMA PATIENT PAGE| Digestive System Anal Fissure An anal fissure is a tear in the opening of ... anus that can cause pain, itching, and bleeding. Anal fissures are common in infants but less so ...

393

JAMA Patient Page: Subclinical Hypothyroidism  

MedlinePLUS

... the American Medical Association JAMA PATIENT PAGE Subclinical Hypothyroidism T he thyroid gland , a 2-inch-long, ... thyroid to work harder. Subclinical (without obvious symptoms) hypothyroidism (low thyroid function) describes a situation in which ...

394

Time out for patient safety.  

PubMed

"Time out for patient safety" is a simple and effective tool to improve communication among caregivers based on the use of critical language that has been effective in the perioperative setting, airline industry, and military. In the emergency department it is non threatening and focuses attention on safe patient care. "Time out for patient safety" complements the use of other standardized communication techniques such as SBAR in clinical situations in which immediate intervention is mandatory for patient safety.This communication tool was presented to the multidisciplinary staff and has been embedded in the Emergency Department's simulation program for newly graduated nurses. The concept was well received by the group.Future research is needed to address outcomes for effectiveness. PMID:21764112

Meginniss, Anne; Damian, Frances; Falvo, Francine

2012-01-01

395

JAMA Patient Page: Head Lice  

MedlinePLUS

JAMA PATIENT PAGE Head Lice Removal of nits Louse on scalp Nits are tightly attached to strands of hair Lice are free and ... tiny insects that infest the hair on your head, as well as the eyebrows and eyelashes. Tiny ...

396

JAMA Patient Page: Head Injury  

MedlinePLUS

... of the American Medical Association JAMA PATIENT PAGE Head Injury M ore than 1 million head injuries occur every year in the United States. Because head injuries (also known as traumatic brain injuries ) are ...

397

JAMA Patient Page: Myocardial Infarction  

MedlinePLUS

... the American Medical Association JAMA PATIENT PAGE Myocardial Infarction M yocardial infarction , also known as a heart attack, can strike without warning. A myocardial infarction occurs when blood supply to a part of ...

398

Corneal temperature in schizophrenia patients.  

PubMed

Most data imply that dopaminergic transmission is essential for proper hypothalamic-mediated core temperature regulation. Altered central dopaminergic transmission is suggested to be involved in the pathophysiology of schizophrenia. Thus, hypothetically, schizophrenia patients might be at increased risk of developing thermoregulatory dysregulation manifested by alterations in core temperature, as well as in peripheral tissue, the temperature of which has been shown to correlate with core temperature (e.g. cornea). Previous small pilot studies of ours showed that schizophrenia patients may exhibit corneal temperature abnormalities. Hence, we assessed corneal temperature in a controlled sample of drug-free ( n =11) and medicated ( n =28) schizophrenia patients compared to healthy comparison subjects ( n =9), using a FLIR thermal imaging camera. Drug-free schizophrenia patients exhibited significantly higher corneal temperature compared to healthy subjects, typical antipsychotic drug (APD)-treated patients ( n =16) and atypical APD-treated patients ( n =12) (37.08+/-1.46 degrees C vs. 33.37+/-2.51 degrees C, 31.08+/-1.43 degrees C and 31.67+/-0.44 degrees C respectively, p <0.0001; p <0.001 vs. each group separately). The healthy comparison subjects and the atypical APD-treated patients exhibited comparable corneal temperatures and these two groups exhibited higher corneal temperatures compared to the typical APD-treated patients ( p <0.01 and p =0.051 respectively). In conclusion, this study indicates that drug-free schizophrenia patients exhibit substantially higher corneal temperature compared to healthy comparison subjects or medicated patients, and that APDs may decrease corneal temperature either to normal (atypical APD) or to subnormal (typical APD) values. The relevance of these phenomena to the pathophysiology of schizophrenia, the biological mechanism underlying drug-induced corneal temperature alterations, the possible role of temperature-lowering drugs (neuroleptics or non-neuroleptics) on schizophrenic psychosis as well as the role of corneal temperature as a tool to evaluate adherence to APD treatment merit further investigation via larger samples of both medicated and drug-free schizophrenia patients compared to matched controlled subjects. PMID:15927092

Shiloh, Roni; Munitz, Hanan; Portuguese, Shirley; Gross-Isseroff, Ruth; Sigler, Mayanit; Bodinger, Liron; Katz, Nachum; Stryjer, Rafael; Hermesh, Haggai; Weizman, Abraham

2005-12-01

399

Patient safety in peritoneal dialysis.  

PubMed

Peritoneal dialysis (PD) is effective and safe when patients and caregivers understand the best practices. Health care teams responsible for PD must act in a coordinated and consistent manner to ensure the most effective outcomes. This chapter will review the evidence for PD and discuss the safety implications of the phases of PD from patient selection to education to maintenance. © 2015 S. Karger AG, Basel. PMID:25676302

Slakey, Douglas P; Davidson, Ingemar

2015-01-01

400

Nutritional Considerations for Cancer Patients  

PubMed Central

Although weight loss is a frequent, though not invariable, component of the cancer syndrome, the associated malnutrition is a poor prognostic sign among both children and adults. This article describes the possible mechanisms of cancer cachexia; reviews the present state of nutritional support in cancer patients; identifies nutritional problems and workable approaches during the pre- and post-treatment periods; discusses the unconventional nutritional practices commonly encountered and lists resource materials for patients and families. PMID:21274086

Chen, Angela

1985-01-01

401

Alexithymia in chronic urticaria patients  

Microsoft Academic Search

Alexithymia has been described as an important dimension in several medical and psychiatric diseases. Chronic urticaria (CU) is a chronic condition, in which treatment is difficult. Our aim is to determine the prevalence of alexithymia traits in patients with CU, and to identify the relationships between alexithymia and psychological variables and quality-of-life dimensions. Fifty-five sequential CU patients in a faculty

Filipe Barbosa; João Freitas; Antonio Barbosa

2011-01-01

402

Patient Simulators Train Emergency Caregivers  

NASA Technical Reports Server (NTRS)

Johnson Space Center teamed up with Sarasota, Florida-based METI (now CAE Healthcare) through the STTR program to ruggedize the company’s patient simulators for training astronauts in microgravity environments. The design modifications were implemented in future patient simulators that are now used to train first responders in the US military as well as fire departments and other agencies that work in disaster zones.

2014-01-01

403

Colorectal Surgery in Cirrhotic Patients  

PubMed Central

Patients with cirrhosis have a greater risk of morbidity and mortality following colorectal surgery. Therefore, preoperative medical optimization and risk assessment using criteria such as the MELD score are vital in preventing complications. Some risk factors include age, urgency of surgery, and ASA score. Postoperative morbidity and mortality are related to portal hypertension, ascites, infection, and anastomotic and stomal complications. This review highlights the assessment of risk and perioperative management of cirrhotic patients undergoing colorectal surgery. PMID:24550693

Steinhagen, Randolph M.

2014-01-01

404

Prostatitis in the Immunocompromised Patient  

Microsoft Academic Search

\\u000a Prostatitis in the immunocompromised patient can be challenging for the caregiver. The immunocompromised state (solid-organ\\u000a transplant, steroid use) of such patients can make them susceptible to organisms for which the physician is not as familiar\\u000a in terms of presentation, diagnosis, and treatment. The following chapter will review the current literature on fungal, viral,\\u000a parasitic, and bacterial infections of the prostate

Alain J. Duclos

405

Pharmacometrics: Focus on the Patient  

PubMed Central

Pharmacometrics, whether using simple or complex models, has contributed to rational and efficient drug development,1–3 with the main focus on early drug development.4 This article describes why opportunities more directly focused on the patient abound in late stage development, illustrating the concept with three innovative examples which focus on benefits to patients, enabling drugs that are truly efficacious to reach the market faster in diseases with high unmet medical needs, while maintaining adequate safety.

Dumitrescu, T Pene; Fossler, MJ; Schmith, VD

2015-01-01

406

Hepatitis C in hemodialysis patients  

PubMed Central

Despite reduction of hepatitis C prevalence after recognition of the virus and testing of blood products, hemodialysis (HD) patients still comprise a high risk group. The natural history of hepatitis C virus (HCV) infection in dialysis is not fully understood while the clinical outcome differs from that of the general population. HD patients show a milder liver disease with lower aminotransferase and viral levels depicted by milder histological features on liver biopsy. Furthermore, the “silent” clinical course is consistent with a slower disease progression and a lower frequency of cirrhosis and hepatocellular carcinoma. Potential explanations for the “beneficial” impact of uremia and hemodialysis on chronic HCV infection are impaired immunosurveillance leading to a less aggressive host response to the virus and intradialytic release of “hepatoprotective” cytokines such as interferon (IFN)-? and hepatocyte growth factor. However, chronic hepatitis C is associated with a higher liver disease related cardiovascular and all-cause mortality of HD patients. Therapy is indicated in selected patients groups including younger patients with low comorbidity burden and especially renal transplant candidates, preferably after performance of a liver biopsy. According to current recommendations, choice of treatment is IFN or pegylated interferon with a reported sustained viral response at 30%-40% and a withdrawal rate ranging from 17% to 30%. New data regarding combination therapy with low doses of ribavirin which provide higher standard variable rates and good safety results, offer another therapeutic option. The new protease inhibitors may be the future for HCV infected HD patients, though data are still lacking. PMID:25848478

Marinaki, Smaragdi; Boletis, John N; Sakellariou, Stratigoula; Delladetsima, Ioanna K

2015-01-01

407

OPSI threat in hematological patients  

PubMed Central

Overwhelming post-splenectomy infection (OPSI) is a rare medical emergency, mainly caused by encapsulated bacteria, shortly progressing from a mild flu-like syndrome to a fulminant, potentially fatal, sepsis. The risk of OPSI is higher in children and in patients with underlying benign or malignant hematological disorders. We retrospectively assessed OPSI magnitude in a high risk cohort of 162 adult splenectomized patients with malignant (19%) and non malignant (81%) hematological diseases, over a 25-year period: 59 of them splenectomized after immunization against encapsulated bacteria, and 103, splenectomized in the previous 12-year study, receiving only life-long oral penicillin prophylaxis. The influence of splenectomy on the immune system, as well as the incidence, diagnosis, risk factors, preventive measures and management of OPSI are also outlined. OPSI occurred in 7 patients (4%) with a median age of 37 years at time interval from splenectomy ranging from 10 days to 12 years. All OPSIs occurred in non immunized patients, except one fatal Staphylococcus aureus -mediated OPSI in a patient adequately immunized before splenectomy. Our analysis further provides evidence that OPSI is a lifelong risk and that current immune prophylaxis significantly decreases OPSI development. Improvement in patients’ education about long-term risk of OPSI and increased physician awareness to face a potentially lethal medical emergency, according to the current surviving sepsis guidelines, represent mandatory strategies for preventing and managing OPSI appropriately. PMID:24251241

Serio, B; Pezzullo, L; Giudice, V; Fontana, R; Annunziata, S; Ferrara, I; Rosamilio, R; De Luca, C; Rocco, M; Montuori, N; Selleri, C

408

[Delusion in the critical patient].  

PubMed

Delirium, the acute confusional syndrome, is a common although infradiagnosed problem in the critically ill patient, especially the hypoactive subtype. Risk factors for delirium are previous cognitive disturbances, some comorbidities, ambiental factors and the acute organic alterations of critical illness. Delirium is associated to an increase in short and long term mortality, prolongation of mechanical ventilation, increased Intensive Care Unit (ICU) and hospital length of stay, and cognitive impairment after hospital discharge. In the last years several tools have been developed to detect delirium in critically ill patients. The Intensive Care Delirium Screening Checklist (ICDSC) and the Confusion Assessment Method for ICU patients (CAM-ICU) have been validated and are useful even in patients receiving mechanical ventilation. Some interventions on specific risk factors can decrease the incidence of delirium in hospitalized patients. Treatment of delirium is based on the identification and correction of contributing factors, the introduction of support measures, and pharmacological therapy for symptomatic control. Halloperidol is the first line therapy of delirium in the critically ill patient, while experience with atypical neuroleptics and other drugs is limited, precluding to do recommendations about its use. Neuroleptic drugs can produce severe side effects and need careful dosage and monitoring. When agitation is important, can be necessary the simultaneous use of benzodiazepines or propofol, and some times, the temporal and protocolized application of physical restraints. PMID:18405541

Palencia-Herrejón, E; Romera, M A; Silva, J A

2008-02-01

409

21 CFR 880.2720 - Patient scale.  

Code of Federal Regulations, 2010 CFR

... 2010-04-01 2010-04-01 false Patient scale. 880.2720 Section 880.2720...Personal Use Monitoring Devices § 880.2720 Patient scale. (a) Identification. A patient scale is a device intended for medical...

2010-04-01

410

Organ Transplant Patients and Fungal Infections  

MedlinePLUS

... CDC.gov . Fungal Diseases Share Compartir Organ Transplant Patients and Fungal Infections As an organ transplant patient, ... of Page Preventing fungal infections in organ transplant patients Fungi are difficult to avoid because they are ...

411

Travel Tips: A Guide for Kidney Patients  

MedlinePLUS

... NKF Store Featured Story Are you a dialysis patient? Sign up for our FREE magazine, Kidney Living ... here Home » Travel Tips: A Guide for Kidney Patients For many patients who are on dialysis or ...

412

42 CFR 2.14 - Minor patients.  

Code of Federal Regulations, 2010 CFR

...2010-10-01 2010-10-01 false Minor patients. 2.14 Section 2.14 Public Health...CONFIDENTIALITY OF ALCOHOL AND DRUG ABUSE PATIENT RECORDS General Provisions § 2.14 Minor patients. (a) Definition of minor....

2010-10-01

413

Depression and Anxiety in Migraine Patients  

MedlinePLUS

... Depression and Anxiety in Migraine Patients Print Email Depression and Anxiety in Migraine Patients ACHE Newsletter Sign ... newsletter by entering your e-mail address below. Depression and Anxiety in Migraine Patients Todd A. Smitherman, ...

414

Antimicrobial Dose in Obese Patient  

PubMed Central

Introduction Obesity is a chronic disease that has become one of major public health issue in Malaysia because of its association with other disease states including cardiovascular disease and diabetes. Despite continuous efforts to educate the public about the health risks associated with obesity, prevalence of the disease continues to increase. Dosing of many medications are based on weight, limited data are available on how antimicrobial agents should be dosed in obesity. The aim of this case presentation is to discuss dose of antibiotic in obese patient. Case report: Patient: GMN, Malay, Female, 45 year old, 150kg, transferred from medical ward to ICU with problems of fever, orthopnea, sepsis secondary to nosocomial pneumonia. She was admitted to hospital a week ago for SOB on exertion, cyanosis, mildly dyspneic, somasthenia, bilateral ankle swelling. There was no fever, cough, chest pain, clubbing, flapping tremor. Her grand father has pre-morbid history of obesity, HPT, DM and asthma. She was non alcoholic, smoker, and not on diet control. The diagnosis Pickwickian syndrome was made. Patient was treated with IV Dopamine 11mcg/kg/min, IV Morphine 4mg/h. IV GTN 15mcg/min, IV Ca gluconate 10g/24h for 3/7, IV Zantac 50mg tds, IV Augmentin 1.2g tds, IV Lasix 40mg od, IV Plasil 10mg tds, S.c heparin 5000IU bd. patient become stable and moved to medical ward to continue her treatment. Discussion: The altered physiologic function seen in obese patients is a concern in patients receiving antimicrobial agents because therapeutic outcomes depend on achieving a minimum inhibitory concentration (MIC). The therapeutic effect of any drug can be altered when any of the 4 pharmacokinetic processes (absorption, distribution, metabolism, or elimination) are altered. Decreased blood flow rates and increased renal clearance in obese patients can affect drug distribution and elimination. Changes in serum protein levels can change the metabolism and distribution of drugs that are highly protein bound; the effects of these physiologic differences should be considered when administrating antimicrobial agents in obese patients. Conclusion: Generally this patient was moderately well managed in view of inappropriate combination of antibiotic, duplication or unnecessary use of antibiotic for treatment of sepsis, more clinical studies are needed to determine antibiotic dose in obese patient.

Kassab, Sawsan; Syed Sulaiman, Syed Azhar; Abdul Aziz, Noorizan

2007-01-01

415

Organ Transplant Patients: Pet Safety Tips  

MedlinePLUS

... Infants and Young Children Publications & Materials Organ Transplant Patients Recommend on Facebook Tweet Share Compartir Pet Safety Tips Patients who have received organ transplants are more likely ...

416

Mongolian spots: How important are they?  

PubMed

Mongolian spots (MS) are congenital birthmarks seen most commonly over the lumbosacral area. They are bluish-green to black in color and oval to irregular in shape. They are most commonly found in individuals of African or Asian ethnic background. Although these lesions resolve by one to two years of age, widespread, extrasacral and dark colored MS sometimes persist into adulthood. Aberrant MS over occiput, temple, mandibular area, shoulders and limbs may be confused with other dermal melanocytoses and bruises secondary to child abuse, thus necessitating documentation at birth. Although traditionally believed to be benign in nature, they have now been shown to co-exist with inborn errors of metabolism, most commonly GM1 gangliosidosis and mucopolysaccharidosis type?I?(Hurler's disease), followed by mucopolysaccharidosis type II (Hunter's syndrome), mucolipidosis, Niemann-Pick disease and mannosidosis. They have also been seen to co-exist with various vascular or other pigmented birthmarks like café-au-lait macules. Co-existing Mongolian spots and vascular birthmarks like nevus flammeus, nevus anemicus or nevus spilus is termed as phakomatosis pigmentovascularis. This review focuses on the important associations of Mongolian spots and stresses upon the importance of screening babies with extensive MS. PMID:24340274

Gupta, Divya; Thappa, Devinder Mohan

2013-11-16

417

Mongolian spots: How important are they?  

PubMed Central

Mongolian spots (MS) are congenital birthmarks seen most commonly over the lumbosacral area. They are bluish-green to black in color and oval to irregular in shape. They are most commonly found in individuals of African or Asian ethnic background. Although these lesions resolve by one to two years of age, widespread, extrasacral and dark colored MS sometimes persist into adulthood. Aberrant MS over occiput, temple, mandibular area, shoulders and limbs may be confused with other dermal melanocytoses and bruises secondary to child abuse, thus necessitating documentation at birth. Although traditionally believed to be benign in nature, they have now been shown to co-exist with inborn errors of metabolism, most commonly GM1 gangliosidosis and mucopolysaccharidosis type?I?(Hurler’s disease), followed by mucopolysaccharidosis type II (Hunter’s syndrome), mucolipidosis, Niemann-Pick disease and mannosidosis. They have also been seen to co-exist with various vascular or other pigmented birthmarks like café-au-lait macules. Co-existing Mongolian spots and vascular birthmarks like nevus flammeus, nevus anemicus or nevus spilus is termed as phakomatosis pigmentovascularis. This review focuses on the important associations of Mongolian spots and stresses upon the importance of screening babies with extensive MS. PMID:24340274

Gupta, Divya; Thappa, Devinder Mohan

2013-01-01

418

Patient perspectives on radiation dose.  

PubMed

People with genetic cancer syndromes have a special interest in imaging. They also have special risk factors with respect to radiation. They need to utilize the potential of imaging while keeping in mind concerns about cumulative radiation exposure. Before imaging, early detection of problems was limited. With imaging, issues can be identified when they are small and a good plan of action can be developed early. Operations can be planned and metastatic cancer avoided. The positive contribution of imaging to the care of these patients can be profound. However, this additional surveillance is not without cost. An average patient with 1 of these syndromes will undergo 100 or more scans in their lifetime. Imaging professionals should be able to describe the risks and benefits of each scan in terms that the patient and the ordering physician can understand to make smart decisions about the ordering of scans. Why CT versus MRI? When are x-ray or ultrasound appropriate, and when are they not? What are the costs and the medical risks for the patient? What value does this picture add for the physician? Is there a way to answer the medical question with a test other than a scan? Medicine is a team sport, and the patient is an integral member of the team. PMID:24589397

Graff, Joyce

2014-03-01

419

Prescribing and partnership with patients  

PubMed Central

There have been widespread changes in society and the roles of professionals. This change is also reflected in health care, where there is now acceptance of the need to involve patients in decision making. In prescribing specifically, the concordance agenda was developed alongside these initiatives to encourage improved medication taking and reduce wastage. However the extent to which these partnerships are delivered in practice remains unclear. This paper explores some of the issues to be considered when preparing patients and professionals for partnership and summarizes the limited evidence of barriers to, and benefits of, this approach. Firstly patients must be given the confidence, skills and knowledge to be partners. They need information about medicines, provided in ways known to be acceptable to them. Likewise professionals may need new skills to be partners. They need to understand the patient agenda and may need training and support to change the ways in which they consult with patients. There are also practical issues such as the perceived increase in time taken when consulting in partnership mode, room layout, computer interfaces and record keeping. Health care professionals other than doctors are also expected to behave in partnership mode, whether this is as prescribers in their own right or in supporting the prescribing of others. Whilst much has been claimed for the benefit of partnership approaches, hard evidence is limited. However whilst there is still much more to understand there will be no going back to the paternalistic model of the mid 20th century. PMID:22621201

Bond, Christine; Blenkinsopp, Alison; Raynor, David K

2012-01-01

420

Aztreonam pharmacokinetics in burn patients.  

PubMed Central

The pharmacokinetics of aztreonam in eight adult patients with severe burn injuries (total body surface area burn, 49% +/- 21% [mean +/- standard deviation]) were studied. The time of initiation of study following burn injury was 7.0 +/- 1.4 days. Four patients at first dose and at steady state were studied. Aztreonam concentrations were measured by high-performance liquid chromatography, and a two-compartment model was used to fit the data. No significant differences in any pharmacokinetic parameters between first dose and steady state were observed. Volume of distribution of the central compartment after first dose (0.14 liters/kg) and volume of distribution at steady state (0.31 liters/kg) were approximately 30% higher than those reported for other patient populations. Total drug clearance and renal drug clearance when normalized to creatinine clearance (CLCR) were similar to those previously reported for other critically ill patients. CLCR was strongly correlated with renal drug clearance (r = 0.94) and total drug clearance (r = 0.95). The extent and degree of burn (percent second or third degree burn) were poorly correlated with all pharmacokinetic parameters with the exception of the volume of distribution at steady state, which was correlated with both total body surface area burn (r = 0.95) and percent second degree burn (r = 0.83). Aztreonam pharmacokinetics are altered as a result of thermal injury; however, CLCR can be used to assess the clearance of aztreonam in burn patients. PMID:2014982

Friedrich, L V; White, R L; Kays, M B; Brundage, D M; Yarbrough, D

1991-01-01

421

Do catheters harm the patient?  

PubMed

There is an increasing use of central venous catheters (CVCs) as a first-line vascular access in incident hemodialysis (HD) patients. CVCs are associated with short-term complications related to the catheter insertion procedure and with long-term complications as a consequence of the intravascular interaction of catheter material with the venous endothelium. Removal of CVCs is also associated with specific risks, such as pulmonary or air embolism. Bacteremia and sepsis, however, are the most important risks associated with CVCs. In incident HD patients, the mortality risk from infection is highest during the first 6 months after dialysis initiation, and has steadily increased over the last decade. The relative risk for infection from CVCs in HD patients now clearly exceeds the risk for catheter-related infections in peritoneal dialysis (PD) patients. CVCs should therefore always be the last preference for vascular access in HD. The option for PD should always be evaluated before using CVCs as a permanent vascular access in end-stage renal disease patients. PMID:21625094

Kuhlmann, Martin K

2011-01-01

422

Creating Simulated Microgravity Patient Models  

NASA Technical Reports Server (NTRS)

The Medical Operational Support Team (MOST) has been tasked by the Space and Life Sciences Directorate (SLSD) at the NASA Johnson Space Center (JSC) to integrate medical simulation into 1) medical training for ground and flight crews and into 2) evaluations of medical procedures and equipment for the International Space Station (ISS). To do this, the MOST requires patient models that represent the physiological changes observed during spaceflight. Despite the presence of physiological data collected during spaceflight, there is no defined set of parameters that illustrate or mimic a 'space normal' patient. Methods: The MOST culled space-relevant medical literature and data from clinical studies performed in microgravity environments. The areas of focus for data collection were in the fields of cardiovascular, respiratory and renal physiology. Results: The MOST developed evidence-based patient models that mimic the physiology believed to be induced by human exposure to a microgravity environment. These models have been integrated into space-relevant scenarios using a human patient simulator and ISS medical resources. Discussion: Despite the lack of a set of physiological parameters representing 'space normal,' the MOST developed space-relevant patient models that mimic microgravity-induced changes in terrestrial physiology. These models are used in clinical scenarios that will medically train flight surgeons, biomedical flight controllers (biomedical engineers; BME) and, eventually, astronaut-crew medical officers (CMO).

Hurst, Victor; Doerr, Harold K.; Bacal, Kira

2004-01-01

423

Mismanagement of a hypochondriacal patient  

PubMed Central

Hypochondriasis is a persistent preoccupation that despite appropriate medical evaluations and assurance of patient's physical health, the patient insists on having a serious disease. The case which is discussed in this article is a 39-years-old woman that hospitalized for half of her life and no one can perceive her disorder according to her assertions. The mentioned case is a “difficult patient” with fear of oxygen shortage and being choked (Pnigophobia) which leads to continuous tendency to wear oxygen device even during sleep. There is no benefit in exaggerating her condition for herself so there is no fictitious disorder considered. During the therapy she has been assured that she does not have a serious disease and she has learnt to decrease oxygen intake and breath with his mouth. The point that makes this study different from the others is that most of hypochondriacal patients have a fear of getting HIV, cancers, hepatitis and MS but our patient has phobia of pulmonary embolism. PMID:25709989

Bidaki, Reza; Mahmoudi, Maryam; Khalili, Behrang; Abedi, Mostafa; Golabbakhsh, Aryan; Haghshenas, Alireza; Sadeghi, Ali; Tabibian, Seyed Reza; Mirhosseini, Seyyed Mohammad Mahdy

2015-01-01

424

[Personality picture of gout patients].  

PubMed

41 male patients (from the Medical Polyclinic of the University of Munich) suffering from gout have been studied with the semi-standardized psychoanalytic interview and psychological test methods. The result was that all of the patients had a pathologic narcissistic personality. They could be divided up into two groups: two thirds of the patients corresponded with the "philobats" and one third with the "oknophiles" of Balint's concept. Some aspects of the interview data could be verified by the standardized psychological tests. Beyond the metaphoric classification with Balint's concept it was interesting to find parallels to M. Mahler's observations on the mother-child-relation. Corresponding interpretations were possible. Questions concerning the illness behavior, the first attack of the gout together with the psychological conflict were discussed. Further research programs are considered necessary. Nevertheless there are reasons to presume that gout is a multifactorial disease with alimentary, genetic and psychological aetiopathogenetic conditions. PMID:7314972

Klussmann, R

1981-01-01

425

[Asplenia in the Hodgkin's patient].  

PubMed

FEWER INDICATIONS AFTER SPLENECTOMY: Real therapeutic progress has been achieved over the last fifty years for patients with Hodgkin's disease known for their chronic immunodepression. Since the advent of effective chemotherapy protocols such as ABVD, and more recently intensive chemotherapy completed as needed with an autograft, splenectomy is no longer performed for therapeutic purposes but may be indicated for its contribution to diagnosis. STRATIFICATION OF RISK OF ASPLENISM: There remain however several questions concerning the infectious complications in these patients given chemotherapy and splenic radiotherapy. One of the objectives of this work was to propose a stratification of risk of asplenism as a function of treatments administered, the level of initial immunodepression, and the age of the patient. PMID:14631638

Gardembas-Pain, M; Mege, M; Pabot du Chatelard, P

2003-09-01

426

The diabetic patient in Ramadan  

PubMed Central

During the month of Ramadan, all healthy, adult Muslims are required to fast from dawn to sunset. Fasting during Ramadan involves abstaining from food, water, beverages, smoking, oral drugs, and sexual intercourse. Although the Quran exempts chronically ill from fasting, many Muslims with diabetes still fast during Ramadan. Patients with diabetes who fast during the month of Ramadan can have acute complications. The risk of complications in fasting individuals with diabetes increases with longer periods of fasting. All patients with diabetes who wish to fast during Ramadan should be prepared by undergoing a medical assessment and engaging in a structured education program to undertake the fast as safely as possible. Although some guidelines do exist, there is an overwhelming need for better designed clinical trials which could provide us with evidence-based information and guidance in the management of patients with diabetes fasting Ramadan. PMID:24761380

Chamsi-Pasha, Hassan; Aljabri, Khalid S.

2014-01-01

427

[Pulmonary toxoplasmosis in immunosuppressed patient].  

PubMed

Pulmonary toxoplasmosis occurs mainly in immunosuppressed patients and its diagnosis mainly relies upon biological confirmation of the parasite. We present the case of a 47 years patient in medullar aplasia after induction chemotherapy for acute lymphoblastic leukemia that developed pulmonary infiltrates of parasitic origin. The diagnosis of pulmonary toxoplasmosis was established after identification of the parasite in brochioloalveolar lavage fluid (BAL) and peripheral blood. Serological tests are of limited utility in immunosuppressed patients. We used classical methods for the diagnosis of parasitosis but they are being replaced by molecular methods. Polymerase Chain Reaction (PCR) allows a highly specific and sensitive diagnosis on any sample but it cannot be performed in any center. PMID:23077869

Rîp?, Carmen; Cojocaru, Ingrid; Luca, Mariana; Luca, C?t?lina Mihaela; Leon, Maria; Bahnea, Roxana-Gabriela

2012-01-01

428

Management of asymptomatic myeloma patients.  

PubMed

Smoldering multiple myeloma is an asymptomatic disorder characterized by the presence of ?30 g/l serum M-protein and/or ?10% bone marrow plasma cell infiltration. The risk of progression to active multiple myeloma is not uniform, and several markers are useful for identifying patients at high risk of this. Although the current standard of care is not to treat, a randomized trial in high-risk smoldering multiple myeloma patients comparing those allocated to receive early treatment with lenalidomide plus dexamethasone with those under observation reported a significant benefit with respect to time to progression and overall survival. We conclude that efforts should be made to identify high-risk patients who are candidates for receiving early treatment before they develop myeloma-related symptomatology. PMID:25363073

Mateos, María-Victoria

2015-02-01

429

Gas Gangrene in Orthopaedic Patients  

PubMed Central

Clostridial myonecrosis is most often seen in settings of trauma, surgery, malignancy, and other underlying immunocompromised conditions. Since 1953 cases of gas gangrene have been reported in orthopaedic patients including open fractures, closed fractures, and orthopaedic surgeries. We present a case of 55-year-old obese woman who developed rapidly progressive gas gangrene in her right leg accompanied by tibial plateau fracture without skin lacerations. She was diagnosed with clostridial myonecrosis and above-the-knee amputation was carried out. This patient made full recovery within three weeks of the initial episode. We identified a total of 50 cases of gas gangrene in orthopaedic patients. Several factors, if available, were analyzed for each case: age, cause of injury, fracture location, pathogen, and outcome. Based on our case report and the literature review, emergency clinicians should be aware of this severe and potentially fatal infectious disease and should not delay treatment or prompt orthopedic surgery consultation. PMID:24288638

Ying, Zhimin; Zhang, Min; Yan, Shigui; Zhu, Zhong

2013-01-01

430

Understanding hypoglycemia in hospitalized patients  

PubMed Central

SUMMARY Controlling blood glucose in hospitalized patients is important as both hyperglycemia and hypoglycemia are associated with increased cost, length of stay, morbidity and mortality. A limiting factor in stringent control is the concern of iatrogenic hypoglycemia. The association of hypoglycemia with mortality has led to clinical guideline changes recommending more conservative glycemic control than had previously been suggested, with the use of patient specific approaches when appropriate. Healthier, stable patients may be managed with stricter control while the elderly and severely ill may be managed less aggressively. While the avoidance of hypoglycemia is essential in clinical practice, recent studies suggest that a higher mortality rate occurs in spontaneous rather than iatrogenic hypoglycemia. Therefore, inpatient hypoglycemia may be viewed more as a biomarker of disease rather than a true cause of fatality. PMID:25197322

Hulkower, Raphael D; Pollack, Rena M; Zonszein, Joel

2014-01-01

431

Seizure Treatment in Transplant Patients  

PubMed Central

Opinion statement Solid organ transplantation is frequently complicated by a spectrum of seizure types, including single partial-onset or generalized tonic-clonic seizures, acute repetitive seizures or status epilepticus, and sometimes the evolution of symptomatic epilepsy. There is currently no specific evidence involving the transplant patient population to guide the selection, administration, or duration of antiepileptic drug (AED) therapy, so familiarity with clinical AED pharmacology and application of sound judgment are necessary for successful patient outcomes. An initial detailed search for symptomatic seizure etiologies, including metabolic, infectious, cerebrovascular, and calcineurin inhibitor treatment-related neuro-toxic complications such as posterior reversible encephalopathy syndrome (PRES), is imperative, as underlying central nervous system disorders may impose additional serious risks to cerebral or general health if not promptly detected and appropriately treated. The mainstay for post-transplant seizure management is AED therapy directed toward the suspected seizure type. Unfavorable drug interactions could place the transplanted organ at risk, so choosing an AED with limited interaction potential is also crucial. When the transplanted organ is dysfunctional or vulnerable to rejection, AEDs without substantial hepatic metabolism are favored in post-liver transplant patients, whereas after renal transplantation, AEDs with predominantly renal elimination may require dosage adjustment to prevent adverse effects. Levetiracetam, gabapentin, pregabalin, and lacosamide are drugs of choice for treatment of partial-onset seizures in post-transplant patients given their efficacy spectrum, generally excellent tolerability, and lack of drug interaction potential. Levetiracetam is the drug of choice for primary generalized seizures in post-transplant patients. When intravenous drugs are necessary for acute seizure management, benzodiazepines and fosphenytoin are the traditional and best evidence-based options, although intravenous levetiracetam, valproate, and lacosamide are emerging options. Availability of several newer AEDs has greatly expanded the therapeutic armamentarium for safe and efficacious treatment of post-transplant seizures, but future prospective clinical trials and pharmacokinetic studies within this specific patient population are needed. PMID:22660960

Shepard, Paul W.

2013-01-01

432

Alexithymia in chronic urticaria patients.  

PubMed

Alexithymia has been described as an important dimension in several medical and psychiatric diseases. Chronic urticaria (CU) is a chronic condition, in which treatment is difficult. Our aim is to determine the prevalence of alexithymia traits in patients with CU, and to identify the relationships between alexithymia and psychological variables and quality-of-life dimensions. Fifty-five sequential CU patients in a faculty ambulatory specialized consultation, with an average age of 44.92, were compared with 31 healthy volunteers. Both groups were studied by means of validated scales for alexithymia (Toronto Alexithymia Scale [TAS-20]), attachment (Adult Attachment Scale-R [AAS-R]), psychopathology (Brief Symptom Inventory [BSI]), personality dimensions (The NEO Five-Factor inventory [NEO-FFI]) and quality of life (Short Form-36 [SF-36]). The classification of CU reactions was obtained from the patient's history, physical examination, laboratory assessment and histopathologic findings. All the patients were under treatment with sedating H1-antihistamines, non-sedating H1-antihistamines combination of H1 and H2 blocker, 2 H1-antihistamines and 3 H1-antihistamines. High traits of alexithymia were found on CU patients (56.9%) as well as high symptom rates of anxiety. Alexithymia traits were significantly positively correlated with insecure attachment styles, with psychopathological symptoms, and with the defense mechanism turn against self. We also reported a significant negative correlation between alexithymia traits and the dimensions of quality of life. Insecure attachment styles were positively correlated with psychopathological symptoms and negatively correlated with quality of life. We did not find significant statistical correlations between alexithymia and clinical variables. CU patients present serious difficulty in dealing with emotion arousal. There is strong evidence of a psychosomatic specificity in CU, with marked alexithymic traits. PMID:21328149

Barbosa, Filipe; Freitas, João; Barbosa, Antonio

2011-03-01

433

Hyponatremia in critically ill patients  

PubMed Central

Context: Hyponatremia is a common electrolyte disturbance in critically ill hence understanding its implications is important. Aims: This study was carried out to ascertain frequency, predisposing conditions and outcome in critically ill patients with hyponatremia on intensive care unit (ICU) admission. Settings and Design: This was an observational, prospective study of a series of ICU patients during a 12-month period. Materials and Methods: The patients were divided into two groups: Hyponatremic (serum sodium < 135 mmol/L) and Eunatremic groups (135-145 mmol/L). Clinical examination included volume status and drug history, biochemistries, clinical diagnosis and cause of hyponatremia. Statistical Analysis Used: Fisher's exact test, unpaired t-tests Wilcoxon ranksum tests, profile-likelihood method, log-rank test and Kaplan—Meier curves were used. P < 0.05 were considered to be statistically significant. Results: In the hyponatremic group, the frequency of hyponatremia on ICU admission was 34.3%, most were euvolumic, 58.96%. Females comprised of 36.5%. The mean age was 60.4 ± 17.2. The Syndrome of inappropriate Antidiuretic Hormone (SIADH) criteria was met in ninety-one patients (36.25%), peumonia being the leading cause of SIADH. Patients with severe sepsis, elective surgery patients, renal failure and heart failure, cirrhosis of liver and subarachnoid hemorrhage were other more likely etiologic causes (P < 0.05). The hyponatremic group spent a longer time in the ICU (P = 0.02), had longer mechanical ventilator days (P < 0.05) and had an increased mortality rate (P = 0.01). Conclusions: Hyponatremia present on admission to the ICU is independent risk factors for poor prognosis. PMID:24678150

Padhi, Rajesh; Panda, Baikuntha Nath; Jagati, Snehalata; Patra, Subhas Chandra

2014-01-01

434

Age-Related Differences in Doctor-Patient Interaction and Patient Satisfaction  

PubMed Central

Background. Relatively little is known about patient characteristics associated with doctor-patient interaction style and satisfaction with the medical visit. Objective. The primary study objectives are to assess: whether doctors interact in a more or less patient-centered style with elderly patients and whether patient age moderates the relationship between interaction style and satisfaction, that is, whether elderly patients are more or less satisfied with patient-centered medical encounters. Methods. We collected pre- and post-visit questionnaire data from 177 patients at a large family medicine clinic. We audiotaped the encounters between doctors and patients. Patient-centered interaction style was measured from coding from the audiotapes of the doctor-patient interactions. Patient satisfaction was measured using the Patient Satisfaction Questionnaire. Results. We found physicians were more likely to have patient-centered encounters with patients over age 65. We also found patient age moderated the association between interaction style and patient satisfaction: older patients were more satisfied with patient-centered encounters. Conclusion. Patient age is associated with style of interaction, which is, in turn, associated with patient satisfaction. Understanding the factors and processes by which doctors and patients interact has the potential to improve many facets of health care delivery. PMID:22007206

Peck, B. Mitchell

2011-01-01

435

This chronic patient becomes a humanistic patient who helps clinicians.  

PubMed

A historian of aging, privileged to work with an interdisciplinary team of caregivers and researchers in a division of geriatric and palliative care of a major medical school and teaching hospital, discovers that his history of chronic illnesses secures him a useful role as a humanistic patient who helps clinicians to respond to the concerns, fears, and needs of aging Boomers. PMID:23017615

Achenbaum, W Andrew

2012-11-01

436

Do patient autonomy preferences matter? Linking patient-centered care to patient–physician relationships and health outcomes  

Microsoft Academic Search

As health care systems seek to provide patient-centered care as a cornerstone of quality, the link between patient-centeredness and patient outcomes is a concern. Past research reveals inconsistent findings regarding the impact of patient-centeredness on patient outcomes, and few studies have investigated the factors that moderate this relationship. Most studies have used self-rated outcomes on a cross-sectional basis, even though

Yin-Yang Lee; Julia L. Lin

2010-01-01

437

Space Technology for Patient Monitoring  

NASA Technical Reports Server (NTRS)

A contract for the development of an astronaut monitoring system in the early days of the space program provided Mennen Medical, Inc. with a foundation in telemetry that led to the development of a computerized medical electronic system used by hospitals. Mennen was the first company to adopt solid state design in patient monitoring and to offer multipatient telemetry monitoring. Telemetry converts instrument data to electrical signals and relays them to a remote receiver where they are displayed. From a central station, a nurse can monitor several patients. Company products include VISTA systems and Horizon 2000 Monitor.

1989-01-01

438

Perverse defenses in neurotic patients.  

PubMed

Distinguishing perverse defenses from the concept of obligatory perversion allows perverse defenses to be examined in neurotic patients. Perverse defenses against reality, one's conflicts, and relationships with others are connected with affect intolerance, difficulty with analytic collaboration, and analytic impasse. Perverse defenses, including the cultivation of states of distraction, excitement, and pomposity, as well as perverse sadomasochistic relations with others, protect against the unbearable: intense affects, painful ideas, and loving, committed need of a valued, distinct person. Patients' perverse, vindictive refusal to be reasonable provokes perverse countertransference reactions whereby the analyst stands in judgmentally and critically for the seemingly absent demands of reason, morality, and analytic progress. PMID:9934661

Coen, S J

1998-01-01

439

Adrenal masses in neoplastic patients  

Microsoft Academic Search

Background  The incidence of complications resulting from fine-needle biopsy of adrenal masses in patients already treated by radical\\u000a procedures for primitive neoplasms of the lungs and kidneys substantiates our opinion concerning laparoscopy as both a diagnostic\\u000a and therapeutic procedure.\\u000a \\u000a \\u000a \\u000a Methods  We performed 70 laparoscopic adrenalectomies from April 1995 to December 1999. In five patients, the adrenal mass appeared\\u000a at follow-up evaluation in

A. Valeri; A. Borrelli; L. Presenti; M. Lucchese; F. Venneri; M. Mannelli; S. Regio; D. Borrelli

2001-01-01

440

Managing complications in cirrhotic patients  

PubMed Central

Liver cirrhosis is a serious and potentially life-threatening condition. This life-threatening condition usually arises from complications of cirrhosis. While variceal bleeding is the most acute and probably best studied, several other complications of liver cirrhosis are more insidious in their onset but nevertheless more important for the long-term management and outcome of these patients. This review summarizes the topics discussed during the UEG-EASL Hepatology postgraduate course of the United European Gastroenterology Week 2013 and discusses emergency surgical conditions in cirrhotic patients, the management of hepatic encephalopathy, ascites and hepatorenal syndrome, coagulation disorders, and liver cancer. PMID:25653862

Angeli, Paolo; Cordoba, Juan; Farges, Oliver; Valla, Dominique

2015-01-01

441

The patient-sensor interface  

PubMed Central

During the assessment of monitoring equipment on acute medical cases in a general ward, a quantitative investigation of technical faults revealed that 44% of these occurred at the patient-sensor interface. While the attachment of the equipment was accepted by the patient and was suitable for application by nursing staff, this degree of technical breakdown indicates that more progress is necessary in the design of this aspect of monitoring equipment before it is possible to have a reliable system. ImagesFig. 1 PMID:5476136

Crockett, G. S.

1970-01-01

442

How to Feed Cleft Patient?  

PubMed Central

ABSTRACT Cleft lip and palate patients have all rights like other normal individuals, to enjoy the benefits of nourishment. Knowledge has to be there about the different feeding positions like straddle, dancer hand position along with the use of specially designed bottles and nipples. Parent's should be trained about the correct positions of feeding, in extreme of the cases in which parents are not able to follow these instructions, feeding obturators can be given. How to cite this article: Jindal MK, Khan SY. How to Feed Cleft Patient? Int J Clin Pediatr Dent 2013;6(2):100-103. PMID:25206201

Khan, Saima Yunus

2013-01-01

443

[Professionals' reactions to patient's suicide].  

PubMed

Physicians, nurses and social workers have a high risk of being confronted with the suicide of a patient during their career. After such an event they may react with sadness, anger or feelings of helplessness. Acute stress reactions are also observed, with irritability, disordered sleep and intrusive thoughts. Some professionals may fear to take care of suicidal patients. Reactions are particularly intense when there was a strong therapeutic relationship. Clinicians should recognize their need for support and look for help, particularly from colleagues. Such an experience may also help them to accept their limits and to become more vigilant and more sensitive to signs of suicidal risk. PMID:17939528

Kaufmann Didisheim, Nadine; Camus, Didier; Gulfi, Alida; Castelli Dransart, Angela

2007-09-19

444

Infrared-Guided Patient Setup for Lung Cancer Patients  

SciTech Connect

Purpose: To evaluate the utility of an infrared-guided patient setup (iGPS) system to reduce the uncertainties in the setup of lung cancer patients. Methods and Materials: A total of 15 patients were setup for lung irradiation using skin tattoos and lateral leveling marks. Daily electronic portal device images and iGPS marker locations were acquired and retrospectively reviewed. The iGPS-based shifts were compared with the daily electronic portal device image shifts using both the central axis iGPS marker and all five iGPS markers. For shift calculation using the five markers, rotational misalignment was included. The level of agreement between the iGPS and portal imaging to evaluate the setup was evaluated as the frequency of the shift difference in the range of 0-5 mm, 5-10 mm, and >10 mm. Results: Data were obtained for 450 treatment sessions for 15 patients. The difference in the isocenter shifts between the weekly vs. daily images was 0-5 mm in 42%, 5-10 mm in 30%, and >10 mm in 10% of the images. The shifts seen using the iGPS data were 0-5 mm in 81%, 5-10 mm in 14%, and >10 mm in 5%. Using only the central axis iGPS marker, the difference between the iGPS and portal images was <5 mm in 77%, 5-10 mm in 16%, and >10 mm in 7% in the left-right direction and 73%, 18%, and 9% in the superoinferior direction, respectively. When all five iGPS markers were used, the disagreements between the iGPS and portal image shifts >10 mm were reduced from 7% to 2% in the left-right direction and 9% to 3% in the superoinferior direction. Larger reductions were also seen (e.g., a reduction from 50% to 0% in 1 patient). Conclusion: The daily iGPS-based shifts correlated well with the daily electronic portal device-based shifts. When patient movement has nonlinear rotational components, a combination of surface markers and portal images might be particularly beneficial to improve the setup for lung cancer patients.

Lyatskaya, Yulia; James, Steven; Killoran, Joseph H.; Soto, Ricardo; Mamon, Harvey J.; Chin, Lee [Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Boston, MA (United States); Allen, Aaron M. [Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Boston, MA (United States)], E-mail: aallen@lroc.harvard.edu

2008-07-15

445

Hypnotherapy in radiotherapy patients: A randomized trial  

Microsoft Academic Search

Purpose: To determine whether hypnotherapy reduces anxiety and improves the quality of life in cancer patients undergoing curative radiotherapy (RT). Methods and materials: After providing written informed consent, 69 patients were randomized between standard curative RT alone (36 controls) and RT plus hypnotherapy (33 patients). Patients in the hypnotherapy group received hypnotherapy at the intake, before RT simulation, before the

Lukas J. A.. Stalpers; Hanna C. da Costa; Merijn A. E. Merbis; Andries A. Fortuin; Martin J. Muller

2005-01-01

446

The dose of hemodialysis and patient mortality  

Microsoft Academic Search

The dose of hemodialysis and patient mortality. The relationship between the delivered dose of hemodialysis and patient mortality remains somewhat controversial. Several observational studies have shown improved patient survival with higher levels of delivered dialysis dose. However, several other unmeasured variables, changes in patient mix or medical management may have impacted on this reported difference in mortality. The current study

Philip J Held; Friedrich K Port; Robert A Wolfe; David C Stannard; Caitlin E Carroll; John T Daugirdas; Wendy E Bloembergen; Joel W Greer; Raymond M Hakim