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Sample records for gm1 gangliosidosis patients

  1. Filipin recognizes both GM1 and cholesterol in GM1 gangliosidosis mouse brain

    PubMed Central

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

    2011-01-01

    Filipin is an antibiotic polyene widely used as a histochemical marker for cholesterol. We previously reported cholesterol/filipin-positive staining in brain of β-galactosidase (β-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 (β-gal+/−) and GM1 gangliosidosis (β-gal−/−) mice. Total ganglioside content (μg sialic acid/mg protein) was 3-fold and 7-fold greater in the PM and MS fractions, respectively, in βgal−/− mice than in βgal+/− mice. GM1 content was 30-fold and 50-fold greater in the PM and MS fractions, respectively. In contrast, unesterified cholesterol content (μg/mg protein) was similar in the PM and the MS fractions of the βgal−/− and βgal+/− 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 β-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

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

    PubMed Central

    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

    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

  3. MRI/MRS as a surrogate marker for clinical progression in GM1 gangliosidosis.

    PubMed

    Regier, Debra S; Kwon, Hyuk Joon; Johnston, Jean; Golas, Gretchen; Yang, Sandra; Wiggs, Edythe; Latour, Yvonne; Thomas, Sarah; Portner, Cindy; Adams, David; Vezina, Gilbert; Baker, Eva H; Tifft, Cynthia J

    2016-03-01

    Background GM1 gangliosidosis is a lysosomal storage disorder caused by mutations in GLB1, encoding β-galactosidase. The range of severity is from type I infantile disease, lethal in early childhood, to type III adult onset, resulting in gradually progressive neurological symtpoms in adulthood. The intermediate group of patients has been recently classified as having type II late infantile subtype with onset of symptoms at one to three years of age or type II juvenile subtype with symptom onset at 2-10 years. To characterize disease severity and progression, six Late infantile and nine juvenile patients were evaluated using magnetic resonance imaging (MRI), and MR spectroscopy (MRS). Since difficulties with ambulation (gross motor function) and speech (expressive language) are often the first reported symptoms in type II GM1, patients were also scored in these domains. Deterioration of expressive language and ambulation was more rapid in the late infantile patients. Fourteen MRI scans in six Late infantile patients identified progressive atrophy in the cerebrum and cerebellum. Twenty-six MRI scans in nine juvenile patients revealed greater variability in extent and progression of atrophy. Quantitative MRS demonstrated a deficit of N-acetylaspartate in both the late infantile and juvenile patients with greater in the late infantile patients. This correlates with clinical measures of ambulation and expressive language. The two subtypes of type II GM1 gangliosidosis have different clinical trajectories. MRI scoring, quantitative MRS and brain volume correlate with clinical disease progression and may serve as important minimally-invasive outcome measures for clinical trials. © 2015 Wiley Periodicals, Inc. PMID:26646981

  4. Tuning glycosidase inhibition through aglycone interactions: pharmacological chaperones for Fabry disease and GM1 gangliosidosis.

    PubMed

    Aguilar-Moncayo, M; Takai, T; Higaki, K; Mena-Barragán, T; Hirano, Y; Yura, K; Li, L; Yu, Y; Ninomiya, H; García-Moreno, M I; Ishii, S; Sakakibara, Y; Ohno, K; Nanba, E; Ortiz Mellet, C; García Fernández, J M; Suzuki, Y

    2012-07-01

    Competitive inhibitors of either α-galactosidase (α-Gal) or β-galactosidase (β-Gal) with high affinity and selectivity have been accessed by exploiting aglycone interactions with conformationally locked sp(2)-iminosugars. Selected compounds were profiled as potent pharmacological chaperones for mutant lysosomal α- and β-Gal associated with Fabry disease and GM(1) gangliosidosis. PMID:22618082

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

    PubMed

    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

    G(M1)-gangliosidosis is a rare progressive neurodegenerative disorder due to an autosomal recessively inherited deficiency of lysosomal β-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 β-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

  6. Canine GM1-gangliosidosis. A clinical, morphologic, histochemical, and biochemical comparison of two different models.

    PubMed Central

    Alroy, J.; Orgad, U.; DeGasperi, R.; Richard, R.; Warren, C. D.; Knowles, K.; Thalhammer, J. G.; Raghavan, S. S.

    1992-01-01

    The clinical, morphologic, histochemical, and biochemical features of GM1-gangliosidosis in two canine models, English Springer Spaniel (ESS) and Portuguese Water Dog (PWD), have been compared. The disease onset, its clinical course, and survival period of the affected dogs were similar in both models. Skeletal dysplasia was noted radiographically at 2 months of age, whereas at 4 1/2 months of age there was progressive neurologic impairment. However, dwarfism and coarse facial features were seen only in ESS. Both models had similar deficiency in activity of lysosomal beta-galactosidase, but possessed a normal protein activator for GM1-beta-galactosidase. Both models stored GM1-ganglioside, asialo-GM1, and oligosaccharides in brain. Furthermore, only the PWD stored glycoproteins containing polylactosaminoglycans in visceral organs, and neither model stored them in the brain. Morphologically, both models demonstrated similar storage material in multiple tissues and cell types. The ultrastructure of the storage material was cell-type specific and identical in both models. However, some differences in the lectin staining pattern were noted. Our clinical, biochemical, and histochemical findings indicate that PWD and ESS may represent two different mutations of the beta-galactosidase gene. Moreover, the authors conclude that it is difficult, and inappropriate, to apply the human classification of GM1-gangliosidosis (i.e. infantile, juvenile, and adult forms) to these canine models. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 PMID:1546746

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

    PubMed Central

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

    2015-01-01

    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 β-galactosidase (β-gal) +/? and β-gal −/− mice, a model of GM1gangliosidosis. Optic nerve weight was lower in the β-gal −/− mice than in unaffected β-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 β-gal −/− mice. The content of myelin-enriched cerebrosides, sulfatides, and plasmalogen ethanolamines was significantly lower in optic nerve of β-gal −/− mice than in β-gal +/? mice; however, cholesteryl esters were enriched in the β-gal −/− mice. No major abnormalities in these lipids were detected in the sciatic nerve of the β-gal −/− mice. The abnormalities in GM1 and myelin lipids in optic nerve of β-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 β-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 β-gal −/− mice is likely due to the greater glycolipid storage in optic nerve. PMID:25694553

  8. A bicyclic 1-deoxygalactonojirimycin derivative as a novel pharmacological chaperone for GM1 gangliosidosis.

    PubMed

    Takai, Tomoko; Higaki, Katsumi; Aguilar-Moncayo, Matilde; Mena-Barragán, Teresa; Hirano, Yuki; Yura, Kei; Yu, Liang; Ninomiya, Haruaki; García-Moreno, M Isabel; Sakakibara, Yasubumi; Ohno, Kousaku; Nanba, Eiji; Ortiz Mellet, Carmen; García Fernández, José M; Suzuki, Yoshiyuki

    2013-03-01

    Lysosomal β-galactosidase (β-Gal) deficiency causes a group of disorders that include neuronopathic GM1 gangliosidosis and non-neuronopathic Morquio B disease. We have previously proposed the use of small molecule ligands of β-Gal as pharmacological chaperones (PCs) for the treatment of GM1 gangliosidosis brain pathology. Although it is still under development, PC therapy has yielded promising preclinical results in several lysosomal diseases. In this study, we evaluated the effect of bicyclic 1-deoxygalactonojirimycin (DGJ) derivative of the sp(2)-iminosugar type, namely 5N,6S-(N'-butyliminomethylidene)-6-thio-1- deoxygalactonojirimycin (6S-NBI-DGJ), as a novel PC for human mutant β-Gal. In vitro, 6S-NBI-DGJ had the ability to inhibit the activity of human β-Gal in a competitive manner and was able to protect this enzyme from heat-induced degradation. Computational analysis supported that the rigid glycone bicyclic core of 6S-NBI-DGJ binds to the active site of the enzyme, with the aglycone N'-butyl substituent, in a precise E-orientation, located at a hydrophobic region nearby. Chaperone potential profiling indicated significant increases of enzyme activity in 24 of 88 β-Gal mutants, including four common mutations. Finally, oral administration of 6S-NBI-DGJ ameliorated the brain pathology of GM1 gangliosidosis model mice. These results suggest that 6S-NBI-DGJ is a novel PC that may be effective on a broad range of β-Gal mutants. PMID:23337983

  9. Founder mutation causing infantile GM1-gangliosidosis in the Gypsy population.

    PubMed

    Sinigerska, Ivanka; Chandler, David; Vaghjiani, Vijesh; Hassanova, Irfet; Gooding, Rebecca; Morrone, Amelia; Kremensky, Ivo; Kalaydjieva, Luba

    2006-05-01

    The Gypsies are a trans-national founder population of Asian descent, whose genetic heritage is still incompletely characterized. Here, we describe the first founder mutation leading to a lysosomal storage disorder in this population: R59H in GLB1, which causes infantile GM1-gangliosidosis. The R59H carrier rate is approximately 2% in the general Gypsy population and approximately 10% in the Rudari sub-isolate. Haplotype analysis suggests that the Gypsy diaspora may have contributed to the spread of this mutation to South America. PMID:16466959

  10. Serial MRI features of canine GM1 gangliosidosis: a possible imaging biomarker for diagnosis and progression of the disease.

    PubMed

    Hasegawa, Daisuke; Yamato, Osamu; Nakamoto, Yuya; Ozawa, Tsuyoshi; Yabuki, Akira; Itamoto, Kazuhito; Kuwabara, Takayuki; Fujita, Michio; Takahashi, Kimimasa; Mizoguchi, Shunta; Orima, Hiromitsu

    2012-01-01

    GM1 gangliosidosis is a fatal neurodegenerative lysosomal storage disease caused by an autosomal recessively inherited deficiency of β-galactosidase activity. Effective therapies need to be developed to treat the disease. In Shiba Inu dogs, one of the canine GM1 gangliosidosis models, neurological signs of the disease, including ataxia, start at approximately 5 months of age and progress until the terminal stage at 12 to 15 months of age. In the present study, serial MR images were taken of an affected dog from a model colony of GM1 gangliosidosis and 4 sporadic clinical cases demonstrating the same mutation in order to characterize the MRI features of this canine GM1 gangliosidosis. By 2 months of age at the latest and persisting until the terminal stage of the disease, the MR findings consistently displayed diffuse hyperintensity in the white matter of the entire cerebrum on T2-weighted images. In addition, brain atrophy manifested at 9 months of age and progressed thereafter. Although a definitive diagnosis depends on biochemical and genetic analyses, these MR characteristics could serve as a diagnostic marker in suspect animals with or without neurological signs. Furthermore, serial changes in MR images could be used as a biomarker to noninvasively monitor the efficacy of newly developed therapeutic strategies. PMID:22536126

  11. Serial MRI Features of Canine GM1 Gangliosidosis: A Possible Imaging Biomarker for Diagnosis and Progression of the Disease

    PubMed Central

    Hasegawa, Daisuke; Yamato, Osamu; Nakamoto, Yuya; Ozawa, Tsuyoshi; Yabuki, Akira; Itamoto, Kazuhito; Kuwabara, Takayuki; Fujita, Michio; Takahashi, Kimimasa; Mizoguchi, Shunta; Orima, Hiromitsu

    2012-01-01

    GM1 gangliosidosis is a fatal neurodegenerative lysosomal storage disease caused by an autosomal recessively inherited deficiency of β-galactosidase activity. Effective therapies need to be developed to treat the disease. In Shiba Inu dogs, one of the canine GM1 gangliosidosis models, neurological signs of the disease, including ataxia, start at approximately 5 months of age and progress until the terminal stage at 12 to 15 months of age. In the present study, serial MR images were taken of an affected dog from a model colony of GM1 gangliosidosis and 4 sporadic clinical cases demonstrating the same mutation in order to characterize the MRI features of this canine GM1 gangliosidosis. By 2 months of age at the latest and persisting until the terminal stage of the disease, the MR findings consistently displayed diffuse hyperintensity in the white matter of the entire cerebrum on T2-weighted images. In addition, brain atrophy manifested at 9 months of age and progressed thereafter. Although a definitive diagnosis depends on biochemical and genetic analyses, these MR characteristics could serve as a diagnostic marker in suspect animals with or without neurological signs. Furthermore, serial changes in MR images could be used as a biomarker to noninvasively monitor the efficacy of newly developed therapeutic strategies. PMID:22536126

  12. Systemic AAV9 gene transfer in adult GM1 gangliosidosis mice reduces lysosomal storage in CNS and extends lifespan.

    PubMed

    Weismann, Cara M; Ferreira, Jennifer; Keeler, Allison M; Su, Qin; Qui, Linghua; Shaffer, Scott A; Xu, Zuoshang; Gao, Guangping; Sena-Esteves, Miguel

    2015-08-01

    GM1 gangliosidosis (GM1) is an autosomal recessive lysosomal storage disease where GLB1 gene mutations result in a reduction or absence of lysosomal acid β-galactosidase (βgal) activity. βgal deficiency leads to accumulation of GM1-ganglioside in the central nervous system (CNS). GM1 is characterized by progressive neurological decline resulting in generalized paralysis, extreme emaciation and death. In this study, we assessed the therapeutic efficacy of an adeno-associated virus (AAV) 9-mβgal vector infused systemically in adult GM1 mice (βGal(-/-)) at 1 × 10(11) or 3 × 10(11) vector genomes (vg). Biochemical analysis of AAV9-treated GM1 mice showed high βGal activity in liver and serum. Moderate βGal levels throughout CNS resulted in a 36-76% reduction in GM1-ganglioside content in the brain and 75-86% in the spinal cord. Histological analyses of the CNS of animals treated with 3 × 10(11) vg dose revealed increased presence of βgal and clearance of lysosomal storage throughout cortex, hippocampus, brainstem and spinal cord. Storage reduction in these regions was accompanied by a marked decrease in astrogliosis. AAV9 treatment resulted in improved performance in multiple tests of motor function and behavior. Also the majority of GM1 mice in the 3 × 10(11) vg cohort retained ambulation and rearing despite reaching the humane endpoint due to weight loss. Importantly, the median survival of AAV9 treatment groups (316-576 days) was significantly increased over controls (250-264 days). This study shows that moderate widespread expression of βgal in the CNS of GM1 gangliosidosis mice is sufficient to achieve significant biochemical impact with phenotypic amelioration and extension in lifespan. PMID:25964428

  13. Systemic AAV9 gene transfer in adult GM1 gangliosidosis mice reduces lysosomal storage in CNS and extends lifespan

    PubMed Central

    Weismann, Cara M.; Ferreira, Jennifer; Keeler, Allison M.; Su, Qin; Qui, Linghua; Shaffer, Scott A.; Xu, Zuoshang; Gao, Guangping; Sena-Esteves, Miguel

    2015-01-01

    GM1 gangliosidosis (GM1) is an autosomal recessive lysosomal storage disease where GLB1 gene mutations result in a reduction or absence of lysosomal acid β-galactosidase (βgal) activity. βgal deficiency leads to accumulation of GM1-ganglioside in the central nervous system (CNS). GM1 is characterized by progressive neurological decline resulting in generalized paralysis, extreme emaciation and death. In this study, we assessed the therapeutic efficacy of an adeno-associated virus (AAV) 9-mβgal vector infused systemically in adult GM1 mice (βGal−/−) at 1 × 1011 or 3 × 1011 vector genomes (vg). Biochemical analysis of AAV9-treated GM1 mice showed high βGal activity in liver and serum. Moderate βGal levels throughout CNS resulted in a 36–76% reduction in GM1-ganglioside content in the brain and 75–86% in the spinal cord. Histological analyses of the CNS of animals treated with 3 × 1011 vg dose revealed increased presence of βgal and clearance of lysosomal storage throughout cortex, hippocampus, brainstem and spinal cord. Storage reduction in these regions was accompanied by a marked decrease in astrogliosis. AAV9 treatment resulted in improved performance in multiple tests of motor function and behavior. Also the majority of GM1 mice in the 3 × 1011 vg cohort retained ambulation and rearing despite reaching the humane endpoint due to weight loss. Importantly, the median survival of AAV9 treatment groups (316–576 days) was significantly increased over controls (250–264 days). This study shows that moderate widespread expression of βgal in the CNS of GM1 gangliosidosis mice is sufficient to achieve significant biochemical impact with phenotypic amelioration and extension in lifespan. PMID:25964428

  14. 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

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

    2012-01-01

    Deficiencies of lysosomal β-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 β-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 β-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

  15. GM1 gangliosidosis and Morquio B disease: expression analysis of missense mutations affecting the catalytic site of acid beta-galactosidase.

    PubMed

    Hofer, Doris; Paul, Karl; Fantur, Katrin; Beck, Michael; Bürger, Friederike; Caillaud, Catherine; Fumic, Ksenija; Ledvinova, Jana; Lugowska, Agnieszka; Michelakakis, Helen; Radeva, Briguita; Ramaswami, Uma; Plecko, Barbara; Paschke, Eduard

    2009-08-01

    Alterations in GLB1, the gene coding for acid beta-D-galactosidase (beta-Gal), can result in GM1 gangliosidosis (GM1), a neurodegenerative disorder, or in Morquio B disease (MBD), a phenotype with dysostosis multiplex and normal central nervous system (CNS) function. While most MBD patients carry a common allele, c.817TG>CT (p.W273L), only few of the >100 mutations known in GM1 can be related to a certain phenotype. In 25 multiethnic patients with GM1 or MBD, 11 missense mutations were found as well as one novel insertion and a transversion causing aberrant gene products. Except c.602G>A (p.R201H) and two novel alleles, c.592G>T (p.D198Y) and c.1189C>G (p.P397A), all mutants resulted in significantly reduced beta-Gal activities (<10% of normal) upon expression in COS-1 cells. Although c.997T>C (p.Y333H) expressed 3% of normal activity, the mutant protein was localized in the lysosomal-endosomal compartment. A homozygous case presented with late infantile GM1, while a heterozygous, juvenile case carried p.Y333H together with p.R201H. This allele, recently found in homozygous MBD, gives rise to rough endoplasmic reticulum (RER)-located beta-Gal precursors. Thus, unlike classical MBD, the phenotype of heterozygotes carrying p.R201H may rather be determined by poorly active, properly transported products of the counter allele than by the mislocalized p.R201H precursors. PMID:19472408

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

    PubMed

    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

    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

  17. A Duplication in the Canine β-Galactosidase Gene GLB1 Causes Exon Skipping and GM1-Gangliosidosis in Alaskan Huskies

    PubMed Central

    Kreutzer, Robert; Leeb, Tosso; Müller, Gundi; Moritz, Andreas; Baumgärtner, Wolfgang

    2005-01-01

    GM1-gangliosidosis is a lysosomal storage disease that is inherited as an autosomal recessive disorder, predominantly caused by structural defects in the β-galactosidase gene (GLB1). The molecular cause of GM1-gangliosidosis in Alaskan huskies was investigated and a novel 19-bp duplication in exon 15 of the GLB1 gene was identified. The duplication comprised positions +1688–+1706 of the GLB1 cDNA. It partially disrupted a potential exon splicing enhancer (ESE), leading to exon skipping in a fraction of the transcripts. Thus, the mutation caused the expression of two different mRNAs from the mutant allele. One transcript contained the complete exon 15 with the 19-bp duplication, while the other transcript lacked exon 15. In the transcript containing exon 15 with the 19-bp duplication a premature termination codon (PTC) appeared, but due to its localization in the last exon of canine GLB1, nonsense-mediated RNA decay (NMD) did not occur. As a consequence of these molecular events two different truncated GLB1 proteins are predicted to be expressed from the mutant GLB1 allele. In heterozygous carrier animals the wild-type allele produces sufficient amounts of the active enzyme to prevent clinical signs of disease. In affected homozygous dogs no functional GLB1 is synthesized and GM1-gangliosidosis occurs. PMID:15944348

  18. Characterization of beta-galactosidase mutations Asp332-->Asn and Arg148-->Ser, and a polymorphism, Ser532-->Gly, in a case of GM1 gangliosidosis.

    PubMed Central

    Zhang, S; Bagshaw, R; Hilson, W; Oho, Y; Hinek, A; Clarke, J T; Callahan, J W

    2000-01-01

    We have identified and characterized three missense mutations in a patient with type 1 G(M1) gangliosidosis, namely a substitution of G for A at nucleotide position 1044 (G1044-->A; in exon 10) on one allele, which converts Asp(332) into asparagine, and both a mutation (C492-->A in exon 4, leading to the amino acid change of Arg(148)-->Ser) and a polymorphism (A1644-->G in exon 15, leading to a change of Ser(532)-->Gly) on the other allele. This patient had less than 1% residual beta-galactosidase activity and minimally detectable levels of immunoreactive beta-galactosidase protein in fibroblasts. To account for the above findings, a series of expression and immunolocalization studies were undertaken to assess the impact of each mutation. Transient overexpression in COS-1 cells of cDNAs encoding Asp(332)Asn, Arg(148)Ser and Ser(532)Gly mutant beta-galactosidases produced abundant amounts of precursor beta-galactosidase, with activities of 0, 84 and 81% compared with the cDNA clone for wild-type beta-galactosidase (GP8). Since the level of vector-driven expression is much less in Chinese hamster ovary (CHO) cells than in COS-1 cells, and we knew that exogenous beta-galactosidase undergoes lysosomal processing when expressed in these cells, transient expression studies were performed of Arg(148)Ser and Ser(532)Gly, which yielded active forms of the enzyme. In this case, the Arg(148)Ser and Ser(532)Gly products gave rise to 11% and 86% of the control activity respectively. These results were not unexpected, since the Arg(148)Ser mutation introduced a major conformational change into the protein, and we anticipated that it would be degraded in the endoplasmic reticulum (ER), whereas the polymorphism was expected to produce near-normal activity. To examine the effect of the Asp(332)Asn mutation on the catalytic activity, we isolated CHO clones permanently transfected with the Asp(332)Asn and Asp(332)Glu constructs, purified the enzymes by substrate

  19. Molecular epidemiology of canine GM1 gangliosidosis in the Shiba Inu breed in Japan: relationship between regional prevalence and carrier frequency

    PubMed Central

    2013-01-01

    Background Canine GM1 gangliosidosis is a fatal disease in the Shiba Inu breed, which is one of the most popular traditional breeds in Japan and is maintained as a standard breed in many countries. Therefore, it is important to control and reduce the prevalence of GM1 gangliosidosis for maintaining the quality of this breed and to ensure supply of healthy dogs to prospective breeders and owners. This molecular epidemiological survey was performed to formulate an effective strategy for the control and prevention of this disease. Results The survey was carried out among 590 clinically unaffected Shiba Inu dogs from the 8 districts of Japan, and a genotyping test was used to determine nation-wide and regional carrier frequencies. The number and native district of affected dogs identified in 16 years from 1997 to June 2013 were also surveyed retrospectively. Of the 590 dogs examined, 6 dogs (1.02%, 6/590) were carriers: 3 dogs (2.27%, 3/132) from the Kinki district and the other 3 dogs from the Hokkaido, Kanto, and Shikoku districts. The retrospective survey revealed 23 affected dogs, among which, 19 dogs (82.6%) were born within the last 7 years. Of the 23 affected dogs, 12 dogs (52.2%) were from the Kinki district. Pedigree analysis demonstrated that all the affected dogs and carriers with the pedigree information have a close blood relationship. Conclusions Our results showed that the current carrier frequency for GM1 gangliosidosis is on the average 1.02% in Japan and rather high in the Kinki district, which may be related to the high prevalence observed over the past 16 years in this region. This observation suggests that carrier dogs are distributed all over Japan; however, kennels in the Kinki district may face an increased risk of GM1 gangliosidosis. Therefore, for effective control and prevention of this disease, it is necessary to examine as many breeding dogs as possible from all regions of Japan, especially from kennels located in areas with high prevalence

  20. Synthesis of C-5a-chain extended derivatives of 4-epi-isofagomine: Powerful β-galactosidase inhibitors and low concentration activators of GM1-gangliosidosis-related human lysosomal β-galactosidase.

    PubMed

    Thonhofer, Martin; Weber, Patrick; Santana, Andres Gonzalez; Fischer, Roland; Pabst, Bettina M; Paschke, Eduard; Schalli, Michael; Stütz, Arnold E; Tschernutter, Marion; Windischhofer, Werner; Withers, Stephen G

    2016-03-01

    From an easily available partially protected formal derivative of 1-deoxymannojirimycin, by hydroxymethyl chain-branching and further elaboration, lipophilic analogs of the powerful β-d-galactosidase inhibitor 4-epi-isofagomine have become available. New compounds exhibit improved inhibitory activities comparable to benchmark compound NOEV (N-octyl-epi-valienamine) and may serve as leads towards improved and more selective pharmacological chaperones for GM1-gangliosidosis. PMID:26838810

  1. Synthesis of C-5a-substituted derivatives of 4-epi-isofagomine: notable β-galactosidase inhibitors and activity promotors of GM1-gangliosidosis related human lysosomal β-galactosidase mutant R201C.

    PubMed

    Thonhofer, Martin; Weber, Patrick; Gonzalez Santana, Andres; Tysoe, Christina; Fischer, Roland; Pabst, Bettina M; Paschke, Eduard; Schalli, Michael; Stütz, Arnold E; Tschernutter, Marion; Windischhofer, Werner; Withers, Stephen G

    2016-06-24

    From an easily available partially protected analog of 1-deoxy-L-gulo-nojirimycin, by chain-branching at C-4 and suitable modification, lipophilic analogs of the powerful β-D-galactosidase inhibitor 4-epi-isofagomine have been prepared. New compounds exhibit considerably improved inhibitory activities when compared with the unsubstituted parent compound and may serve as leads toward new pharmacological chaperones for GM1-gangliosidosis and Morquio B disease. PMID:27063389

  2. pH-dependent formation of membranous cytoplasmic body-like structure of ganglioside G(M1)/bis(monoacylglycero)phosphate mixed membranes.

    PubMed

    Hayakawa, Tomohiro; Makino, Asami; Murate, Motohide; Sugimoto, Ichiro; Hashimoto, Yasuhiro; Takahashi, Hiroshi; Ito, Kazuki; Fujisawa, Tetsuro; Matsuo, Hirotami; Kobayashi, Toshihide

    2007-01-01

    Membrane structures of the mixtures of ganglioside G(M1) and endosome specific lipid, bis (monoacylglycero) phosphate (BMP, also known as lysobisphosphatidic acid) were examined at various pH conditions by freeze-fracture electron microscopy and small-angle x-ray scattering. At pH 8.5-6.5, a G(M1)/BMP (1:1 mol/mol) mixture formed small vesicular aggregates, whereas the mixture formed closely packed lamellar structures under acidic conditions (pH 5.5, 4.6) with the lamellar repeat distance of 8.06 nm. Since BMP alone exhibits a diffuse lamellar structure at a broad range of pH values and G(M1) forms a micelle, the results indicate that both G(M1) and BMP are required to produce closely stacked multilamellar vesicles. These vesicles resemble membranous cytoplasmic bodies in cells derived from patients suffering from G(M1) gangliosidosis. Similar to G(M1) gangliosidosis, cholesterol was trapped in BMP vesicles in G(M1)- and in a low pH-dependent manner. Studies employing different gangliosides and a G(M1) analog suggest the importance of sugar chains and a sialic acid of G(M1) in the pH-dependent structural change of G(M1)/BMP membranes. PMID:17056735

  3. Genetics Home Reference: GM1 gangliosidosis

    MedlinePlus

    ... Accessibility FOIA Viewers & Players U.S. Department of Health & Human Services National Institutes of Health National Library of Medicine Lister Hill National Center for Biomedical Communications 8600 Rockville Pike, Bethesda, MD 20894, USA HONCode ...

  4. Alterations in cholesterol and ganglioside GM1 content of lipid rafts in platelets from patients with Alzheimer disease.

    PubMed

    Liu, Li; Zhang, Ke; Tan, Liang; Chen, Yu-Hua; Cao, Yun-Peng

    2015-01-01

    The aim of this study was to investigate the changes in the protein, cholesterol, and ganglioside GM1 content of lipid rafts in platelets from patients with Alzheimer disease (AD), and identify potential blood biomarkers of the disease. A total of 31 Chinese patients with AD and 31 aged-matched control subjects were selected. Lipid rafts were isolated from platelets using Optiprep gradient centrifugation. The protein content of lipid rafts was evaluated using Micro BCA assay, the cholesterol content using molecular probes, ganglioside GM1 content using colorimetry and dot-blotting analysis. The results showed that the cholesterol and ganglioside GM1 content of lipid rafts from platelets was significantly higher in patients with AD than aged-matched control subjects, whereas the protein content of lipid rafts did not show any differences between the 2 groups. These results indicate that the increases in the cholesterol and ganglioside GM1 content of lipid rafts from the platelets of patients with AD might serve as a biochemical adjunct to the clinical diagnosis of AD. PMID:24759545

  5. Electroconvulsive therapy treatment of depression in a patient with adult GM2 gangliosidosis.

    PubMed

    Renshaw, P F; Stern, T A; Welch, C; Schouten, R; Kolodny, E H

    1992-03-01

    Adult GM2 gangliosidosis is a rare disorder that often presents with both neurological and psychiatric syndromes. Effective treatment of the psychotic and affective symptoms associated with this disorder has been complicated by poor treatment response and the concern that many psychotropic agents may worsen the underlying gangliosidosis. We report the successful use of electroconvulsive therapy for treatment of severe depression in a young man with adult GM2 gangliosidosis. PMID:1386210

  6. Human monoclonal IgM with autoantibody activity against two gangliosides (GM1 and GD1b) in a patient with motor neuron syndrome.

    PubMed Central

    Jauberteau, M O; Gualde, N; Preud'Homme, J L; Rigaud, M; Gil, R; Vallat, J M; Baumann, N

    1990-01-01

    Small amounts of oligoclonal immunoglobulins were detected by Western blotting in the serum from a patient with motor neuron syndrome. The prominent one, a monoclonal IgM lambda, reacted strongly with the gangliosides GM1 and GD1b and more weakly with asialo GM1, as shown by immunoenzymatic staining of thin-layer chromatograms of gangliosides, ELISA on purified glycolipid coats and immunoadsorption with purified GM1. Affinity-chromatography with purified GM1 resulted in the purification of monoclonal IgM lambda. This purified IgM and its Fab fragments showed the same pattern of reactivity with gangliosides as that observed with whole serum. Such monoclonal IgM could be responsible for motor neuron diseases in some patients with overt or barely detectable monoclonal gammopathies. Images Fig. 2 Fig. 3 PMID:2357844

  7. The GM1 and GM2 Gangliosidoses: Natural History and Progress toward Therapy.

    PubMed

    Regier, Debra S; Proia, Richard L; D'Azzo, Alessandra; Tifft, Cynthia J

    2016-06-01

    The gangliosidoses are lysosomal storage disorders caused by accumulation of GM1 or GM2 gangliosides. GM1 gangliosidosis has both central nervous system and systemic findings; while, GM2 gangliosidosis is restricted primarily to the central nervous system. Both disorders have autosomal recessive modes of inheritance and a continuum of clinical presentations from a severe infantile form to a milder, chronic adult form. Both are devastating diseases without cure or specific treatment however, with the use of supportive aggressive medical management, the lifespan and quality of life has been extended for both diseases. Naturally occurring and engineered animal models that mimic the human diseases have enhanced our understanding of the pathogenesis of disease progression. Some models have shown significant improvement in symptoms and lifespan with enzyme replacement, substrate reduction, and anti-inflammatory treatments alone or in combination. More recently gene therapy has shown impressive results in large and small animal models. Treatment with FDA-approved glucose analogs to reduce the amount of ganglioside substrate is used as off-label treatments for some patients. Therapies also under clinical development include small molecule chaperones and gene therapy. PMID:27491214

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

    PubMed

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

    1980-01-01

    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

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

    PubMed

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

    2009-08-01

    GM2 gangliosidosis (GM2g) is an inherited neurodegenerative disorder caused by deficiency of lysosomal beta-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, respectively. Eleven patients with infantile (n = 6) and juvenile (n = 5) GM2g received oral miglustat at 30-200 mg t.i.d. adjusted to the body surface area. Patients underwent pharmacokinetic assessments on day 1 and at month 3. The pharmacokinetics of miglustat were described by a 2-compartmental model with a lag time, median time to maximum concentration of 2.5 h, and terminal half-life of about 10 h. The pharmacokinetics were time-independent, and did not differ between infantile and juvenile cohorts. The accumulation index was 1.7. Among infantile GM2g patients, the major drug-related adverse events (DRAEs) were abdominal discomfort and flatulence. In the juvenile group, however, the major DRAEs observed were diarrhea and weight loss. One juvenile patient developed peripheral neuropathy, and others showed progression of already established neuropathy, which was judged to be part of the natural progression of the disease. Some mild laboratory abnormalities observed were either transient or attributable to concomitant medications. Miglustat showed similar pharmacokinetic parameters in all patients, with no specific difference between infantile and juvenile forms. Miglustat was shown to be a safe drug, with mild to moderate diarrhea, as an age-dependent DRAE, which was controlled by dietary modification. PMID:19447653

  10. High-throughput imaging method for direct assessment of GM1 ganglioside levels in mammalian cells

    PubMed Central

    Acosta, Walter; Martin, Reid; Radin, David N.; Cramer, Carole L.

    2016-01-01

    GM1-gangliosidosis is an inherited autosomal recessive disorder caused by mutations in the gene GLB1, which encodes acid β-galactosidase (β-gal). The lack of activity in this lysosomal enzyme leads to accumulation of GM1 gangliosides (GM1) in cells. We have developed a high-content-imaging method to assess GM1 levels in fibroblasts that can be used to evaluate substrate reduction in treated GLB1−/− cells [1]. This assay allows fluorescent quantification in a multi-well system which generates unbiased and statistically significant data. Fluorescently labeled Cholera Toxin B subunit (CTXB), which specifically binds to GM1 gangliosides, was used to detect in situ GM1 levels in a fixed monolayer of fibroblasts. This sensitive, rapid, and inexpensive method facilitates in vitro drug screening in a format that allows a high number of replicates using low working volumes. PMID:26958633

  11. High-throughput imaging method for direct assessment of GM1 ganglioside levels in mammalian cells.

    PubMed

    Acosta, Walter; Martin, Reid; Radin, David N; Cramer, Carole L

    2016-03-01

    GM1-gangliosidosis is an inherited autosomal recessive disorder caused by mutations in the gene GLB1, which encodes acid β-galactosidase (β-gal). The lack of activity in this lysosomal enzyme leads to accumulation of GM1 gangliosides (GM1) in cells. We have developed a high-content-imaging method to assess GM1 levels in fibroblasts that can be used to evaluate substrate reduction in treated GLB1(-/-) cells [1]. This assay allows fluorescent quantification in a multi-well system which generates unbiased and statistically significant data. Fluorescently labeled Cholera Toxin B subunit (CTXB), which specifically binds to GM1 gangliosides, was used to detect in situ GM1 levels in a fixed monolayer of fibroblasts. This sensitive, rapid, and inexpensive method facilitates in vitro drug screening in a format that allows a high number of replicates using low working volumes. PMID:26958633

  12. CSF N-glycan profile reveals sialylation deficiency in a patient with GM2 gangliosidosis presenting as childhood disintegrative disorder.

    PubMed

    Barone, Rita; Sturiale, Luisella; Fiumara, Agata; Palmigiano, Angelo; Bua, Rosaria O; Rizzo, Renata; Zappia, Mario; Garozzo, Domenico

    2016-04-01

    Protein N-glycosylation consists in the synthesis and processing of the oligosaccharide moiety (N-glycan) linked to a protein and it serves several functions for the proper central nervous system (CNS) development and function. Previous experimental and clinical studies have shown the importance of proper glycoprotein sialylation for the synaptic function and the occurrence of autism spectrum disorders (ASD) in the presence of sialylation deficiency in the CNS. Late-onset Tay Sachs disease (LOTSD) is a lysosomal disorder caused by mutations in the HEXA gene resulting in GM2-ganglioside storage in the CNS. It is characterized by progressive neurological impairment and high co-occurrence of psychiatric disturbances. We studied the N-glycome profile of the cerebrospinal fluid (CSF) in a 14 year-old patient with GM2-gangliosidosis (LOTSD). At the age of 4, the patient presented regressive autism fulfilling criteria for childhood disintegrative disorder (CDD). A CSF sample was obtained in the course of diagnostic work-up for the suspicion of an underlying neurodegenerative disorder. We found definite changes of CSF N-glycans due to a dramatic decrease of sialylated biantennary and triantennary structures and an increase of asialo-core fucosylated bisected N-glycans. No changes of total plasma N-glycans were found. Herein findings highlight possible relationships between the early onset psychiatric disturbance featuring CDD in the patient and defective protein sialylation in the CNS. In conclusion, the study first shows aberrant N-glycan structures of CSF proteins in LOTSD; unveils possible pathomechanisms of GM2-gangliosidosis; supports existing relationships between neuropsychiatric disorders and unproper protein glycosylation in the CNS. PMID:26286102

  13. Natural History of Infantile GM2 Gangliosidosis

    PubMed Central

    Bley, Annette E.; Giannikopoulos, Ourania A.; Hayden, Doug; Kubilus, Kim; Tifft, Cynthia J.

    2011-01-01

    OBJECTIVE: GM2 gangliosidoses are caused by an inherited deficiency of lysosomal β-hexosaminidase and result in ganglioside accumulation in the brain. Onset during infancy leads to rapid neurodegeneration and death before 4 years of age. We set out to quantify the rate of functional decline in infantile GM2 gangliosidosis on the basis of patient surveys and a comprehensive review of existing literature. METHODS: Patients with infantile GM2 gangliosidosis (N = 237) were surveyed via questionnaire by the National Tay Sachs & Allied Diseases Association (NTSAD). These data were supplemented by survival data from the NTSAD database and a literature survey. Detailed retrospective surveys from 97 patients were available. Five patients who had received hematopoietic stem cell transplantation were evaluated separately. The mortality rate of the remaining 92 patients was comparable to that of the 103 patients from the NTSAD database and 121 patients reported in the literature. RESULTS: Common symptoms at onset were developmental arrest (83%), startling (65%), and hypotonia (60%). All 55 patients who had learned to sit without support lost that ability within 1 year. Individual functional measures correlated with each other but not with survival. Gastric tube placement was associated with prolonged survival. Tay Sachs and Sandhoff variants did not differ. Hematopoietic stem cell transplantation was not associated with prolonged survival. CONCLUSIONS: We studied the timing of regression in 97 cases of infantile GM2 gangliosidosis and conclude that clinical disease progression does not correlate with survival, likely because of the impact of improved supportive care over time. However, functional measures are quantifiable and can inform power calculations and study design of future interventions. PMID:22025593

  14. Deficiency of ganglioside GM1 correlates with Parkinson's disease in mice and humans.

    PubMed

    Wu, Gusheng; Lu, Zi-Hua; Kulkarni, Neil; Ledeen, Robert W

    2012-10-01

    Several studies have successfully employed GM1 ganglioside to treat animal models of Parkinson's disease (PD), suggesting involvement of this ganglioside in PD etiology. We recently demonstrated that genetically engineered mice (B4galnt1(-/-) ) devoid of GM1 acquire characteristic symptoms of this disorder, including motor impairment, depletion of striatal dopamine, selective loss of tyrosine hydroxylase-expressing neurons, and aggregation of α-synuclein. The present study demonstrates similar symptoms in heterozygous mice (HTs) that express only partial GM1 deficiency. Symptoms were alleviated by administration of L-dopa or LIGA-20, a membrane-permeable analog of GM1 that penetrates the blood-brain barrier and accesses intracellular compartments. Immunohistochemical analysis of paraffin sections from PD patients revealed significant GM1 deficiency in nigral dopaminergic neurons compared with age-matched controls. This was comparable to the GM1 deficiency of HT mice and suggests that GM1 deficiency may be a contributing factor to idiopathic PD. We propose that HT mice with partial GM1 deficiency constitute an especially useful model for PD, reflecting the actual pathophysiology of this disorder. The results point to membrane-permeable analogs of GM1 as holding promise as a form of GM1 replacement therapy. PMID:22714832

  15. [Generalized GM1 gangliosidosis. Report of a case and review of the literature].

    PubMed

    Pérez, R; Cuesta, J M; Haro de los Monteros, N; Hernando Mayor y Montes, J C

    1984-05-01

    Authors present the case of a child, daughter of non related parents with neurologic progressive affectation, retina and visceral implication with certain pseudogargolic clinical aspect without near familiar antecedents suggestive of this disease. Biochemistry and histologic studies revealed a B-galactosidase enzyme deficiency and lipidic intracellular increase in different viscera. Biochemistry, hystological and clinical aspects exposed are fundamentally differential of another causes of pseudo-Hurler syndrome. PMID:6433763

  16. Binding of immunoglobulin G antibodies in Guillain-Barré syndrome sera to a mixture of GM1 and a phospholipid: possible clinical implications.

    PubMed

    Kusunoki, Susumu; Morita, Daiji; Ohminami, Shinya; Hitoshi, Seiji; Kanazawa, Ichiro

    2003-03-01

    Anti-GM1 immunoglobulin G (IgG) antibodies are frequently present in sera from patients with Guillain-Barré syndrome (GBS). A previous report on a patient who had a neuropathy with immunoglobulin M (IgM) M-protein binding to a conformational epitope formed by phosphatidic acid (PA) and gangliosides prompted us to investigate the binding of IgG antibodies in GBS sera to a mixture of GM1 and PA (GM1/PA). Of 121 GBS patients, 32 had anti-GM1 IgG antibodies. All 32 also had antibody activity against GM1/PA. Twenty-five (78%) of 32 patients had greater activity against GM1/PA than against GM1 alone. Twelve patients who had no anti-GM1 IgG antibodies had IgG antibody activity against GM1/PA. No GBS patient had IgG antibody against PA alone. In contrast, two rabbit anti-GM1 antisera had greater activity against GM1 alone than against GM1/PA. IgG antibody with greater binding activity against a mixture of GM1 and a phospholipid than against GM1 alone may have an important role in the pathogenesis of GBS and has implications for diagnosis. PMID:12635116

  17. 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

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

    2011-01-01

    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 α or β 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

  18. Passive transfer of IgG anti-GM1 antibodies impairs peripheral nerve repair

    PubMed Central

    Lopez, Pablo H.; Zhang, Gang; Zhang, Jiangyang; Lehmann, Helmar C.; Griffin, John W.; Schnaar, Ronald L.; Sheikh, Kazim A.

    2010-01-01

    Anti-GM1 antibodies are present in some patients with autoimmune neurological disorders. These antibodies are most frequently associated with acute immune neuropathy called Guillain-Barré syndrome (GBS). Some clinical studies associate the presence of these antibodies with poor recovery in GBS. The patients with incomplete recovery have failure of nerve repair, particularly axon regeneration. Our previous work indicates that monoclonal antibodies can inhibit axon regeneration by engaging cell surface gangliosides (Lehmann et al., 2007). We asked whether passive transfer of human anti-GM1 antibodies from patients with GBS modulate axon regeneration in an animal model. Human anti-GM1 antibodies were compared with other GM1 ligands, cholera toxin B subunit and a monoclonal anti-GM1 antibody. Our results show that patient derived anti-GM1 antibodies and cholera toxin β subunit impair axon regeneration/repair after PNS injury in mice. Comparative studies indicated that the antibody/ligand-mediated inhibition of axon regeneration is dependent on antibody/ligand characteristics such as affinity-avidity and fine specificity. These data indicate that circulating immune effectors such as human autoantibodies, which are exogenous to the nervous system, can modulate axon regeneration/nerve repair in autoimmune neurological disorders such as GBS. PMID:20631181

  19. GM1 ganglioside and Alzheimer's disease.

    PubMed

    Yanagisawa, Katsuhiko

    2015-05-01

    Assembly and deposition of amyloid ß-protein (Aß) is an invariable and fundamental event in the pathological process of Alzheimer's disease (AD). To decipher the AD pathogenesis and also to develop disease-modifying drugs for AD, clarification of the molecular mechanism underlying the Aß assembly into amyloid fibrils in the brain has been a crucial issue. GM1-ganglioside-bound Aß (GAß), with unique molecular characteristics such as having an altered conformation and the capability to accelerate Aß assembly, was discovered in an autopsied brain showing early pathological changes of AD in 1995. On the basis of these findings, it was hypothesized that GAß is an endogenous seed for amyloid fibril formation in the AD brain. A body of evidence that supports this GAß hypothesis has been growing over this past 20 years. In this article, seminal GAß studies that have been carried out to date, including recent ones using unique animal models, are reviewed. PMID:25903682

  20. Juvenile-onset G(M2)-gangliosidosis in an African-American child with nystagmus.

    PubMed

    Paciorkowski, Alex R; Sathe, Swati; Zeng, Bei-Jin; Torres, Paola; Rosengren, Sally S; Kolodny, Edwin

    2008-04-01

    G(M2)-gangliosidosis is a neurodegenerative lysosomal disease with several clinical variants. We describe a 2-year-old black child with juvenile-onset disease, who presented with abnormal eye movements and cherry-red spots of the maculae. Mutation analysis of the HEXA gene revealed the patient to be a compound heterozygote (M1V/Y37N). The M1V mutation was previously described in an African-American child with acute infantile G(M2)-gangliosidosis. The Y37N mutation is novel. This combination of mutations is consistent with juvenile-onset disease, and provides further evidence for the association of the M1V mutation with individuals of black ancestry. The presence of oculomotor abnormalities is an unusual finding in this form of G(M2)-gangliosidosis, and adds to the phenotypic spectrum. PMID:18358410

  1. Optimization of GM(1,1) power model

    NASA Astrophysics Data System (ADS)

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

    2013-10-01

    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.

  2. GM1 and GM2 gangliosides: recent developments.

    PubMed

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

    2014-03-01

    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

  3. GM1 Ganglioside: Past Studies and Future Potential.

    PubMed

    Aureli, Massimo; Mauri, Laura; Ciampa, Maria Grazia; Prinetti, Alessandro; Toffano, Gino; Secchieri, Cynthia; Sonnino, Sandro

    2016-04-01

    Gangliosides (sialic acid-containing glycosphingolipids) are abundant in neurons of all animal species and play important roles in many cell physiological processes, including differentiation, memory control, cell signaling, neuronal protection, neuronal recovery, and apoptosis. Gangliosides also function as anchors or entry points for various toxins, bacteria, viruses, and autoantibodies. GM1, a ganglioside component of mammalian brains, is present mainly in neurons. GM1 is one of the best studied gangliosides, and our understanding of its properties is extensive. Simple and rapid procedures are available for preparation of GM1 as a natural compound on a large scale, or as a derivative containing an isotopic radionuclide or a specific probe. Great research interest in the properties of GM1 arose from the discovery in the early 1970s of its role as receptor for the bacterial toxin responsible for cholera pathogenesis. PMID:25762012

  4. Biochemical characterization of GM1 micelles-Amphotericin B interaction.

    PubMed

    Leonhard, Victoria; Alasino, Roxana V; Bianco, Ismael D; Garro, Ariel G; Heredia, Valeria; Beltramo, Dante M

    2015-01-01

    In this work a thorough characterization of the GM1 micelle-Amphotericin B (AmB) interaction was performed. The micelle formation as well as the drug loading occurs spontaneously, although influenced by the physicochemical conditions, pH and temperature. The chromatographic profile of GM1-AmB complexes at different molar ratios shows the existence of two populations. The differential absorbance of GM1, monomeric and aggregate AmB, allowed us to discriminate the presence of all of them in both fractions. Thus, we noted that at higher proportion of AmB in the complex, increases the larger population which is composed mainly of aggregated AmB. The physical behavior of these micelles shows that both GM1- AmB complexes were stable in solution for at least 30 days. However upon freeze-thawing or lyophilization-solubilization cycles, only the smallest population, enriched in monomeric AmB, showed a complete solubilization. In vitro, GM1-AmB micelles were significantly less toxic on cultured cells than other commercial micellar formulations as Fungizone, but had a similar behavior to liposomal formulations as Ambisome. Regarding the antifungal activity of the new formulation, it was very similar to that of other formulations. The characterization of these GM1-AmB complexes is discussed as a potential new formulation able to improve the antifungal therapeutic efficiency of AmB. PMID:25772153

  5. Properties of ganglioside GM1 in phosphatidylcholine bilayer membranes.

    PubMed

    Reed, R A; Shipley, G G

    1996-03-01

    Gangliosides have been shown to function as cell surface receptors, as well as participating in cell growth, differentiation, and transformation. In spite of their multiple biological functions, relatively little is known about their structure and physical properties in membrane systems. The thermotropic and structural properties of ganglioside GM1 alone and in a binary system with 1,2-dipalmitoyl phosphatidylcholine (DPPC) have been investigated by differential scanning calorimetry (DSC) and x-ray diffraction. By DSC hydrated GM1 undergoes a broad endothermic transition TM = 26 degrees C (delta H = 1.7 kcal/mol GM1). X-ray diffraction below (-2 degrees C) and above (51 degrees C) this transition indicates a micellar structure with changes occurring only in the wide angle region of the diffraction pattern (relatively sharp reflection at 1/4.12 A-1 at -2 degrees C; more diffuse reflection at 1/4.41 A-1 at 51 degrees C). In hydrated binary mixtures with DPPC, incorporation of GM1 (0-30 mol%; zone 1) decreases the enthalpy of the DPPC pretransition at low molar compositions while increasing the TM of both the pre- and main transitions (limiting values, 39 and 44 degrees C, respectively). X-ray diffraction studies indicate the presence of a single bilayer gel phase in zone 1 that can undergo chain melting to an L alpha bilayer phase. A detailed hydration study of GM1 (5.7 mol %)/DPPC indicated a conversion of the DPPC bilayer gel phase to an infinite swelling system in zone 1 due to the presence of the negatively charged sialic acid moiety of GM1. At 30-61 mol % GM1 (zone 2), two calorimetric transitions are observed at 44 and 47 degrees C, suggesting the presence of two phases. The lower transition reflects the bilayer gel --> L alpha transition (zone 1), whereas the upper transition appears to be a consequence of the formation of a nonbilayer, micellar or hexagonal phase, although the structure of this phase has not been defined by x-ray diffraction. At > 61 mol % GM

  6. [Serum IgG antibodies to GD1a and GM1 gangliosides in elderly people].

    PubMed

    Kolyovska, V

    2016-01-01

    Nowadays, the percentage of elderly people in society grows. Good nutrition and medical care help older people to have a normal life over 80 to 90 years. In the last ten years it is of critical importance to establish the clinical significance of serum IgG anti-GD1a and anti-GM1 ganglioside antibodies as potential biomarkers for neuronal damage in neurodegenerative diseases and immune-mediated neuropathies and demyelination. In the current study, the diagnostic values of IgG anti-GD1a and anti-GM1 antibodies were determined by the ELISA method in serum samples of 18 elderly patients (71-91 years). Significantly elevated serum IgG anti-GD1a and anti-GM1 antibodies titers were detected only in patients over 80 years. These data suggest that the immune-mediated neuropathies, neurodegeneration and demyelination in healthy elderly occur after 80 years old. Therefore, IgG anti-GD1a and anti-GM1 antibodies can serve as biomarkers, showing the nervous system dysfunction. PMID:26973195

  7. THE EFFECT OF MONOSIALOGANGLYOSIDE (GM-1) ADMINISTRATION IN SPINAL CORD INJURY

    PubMed Central

    BARROS, TARCÍSIO ELOY PESSOA; ARAUJO, FERNANDO FLORES DE; HIGINO, LUCAS DA PAZ; MARCON, RAPHAEL MARTUS; CRISTANTE, ALEXANDRE FOGAÇA

    2016-01-01

    ABSTRACT Objective: To evaluate the effect of monosialoganglioside (GM-1) in spinal cord trauma patients seen in our service who have not been treated with methylprednisolone. Methods: Thirty patients with acute spinal cord trauma were randomly divided into two groups. In Group 1, patients received 200 mg GM-1 in the initial assessment and thereafter received 100 mg intravenous per day for 30 days and Group 2 (control) received saline. Patients were evaluated periodically (at 6 weeks, 6 months, one year and two years), using a standardized neurological assessment of the American Spinal Injury Association / International Spinal Cord Society. Results: The comparative statistical analysis of motor indices, sensitive indices for pain and touch according to the standardization of ASIA / ISCOS showed that the assessments at 6 weeks, 6 months and 2 years, GM-Group 1 patients had higher rates than the control group regarding sensitivity to pain and touch, with no statistically significant difference from the motor index. Conclusion: The functional assessment showed improvement in the sensitive indices of patients treated with GM1 after post-traumatic spinal cord injury compared to patients who received placebo. Level of Evidence IV, Prospective Case Studies Series. PMID:27217811

  8. Late-onset GM2 gangliosidosis presenting as burning dysesthesias.

    PubMed

    Chow, G C; Clarke, J T; Banwell, B L

    2001-07-01

    Two brothers with a painful neuropathy as a component of late-onset GM2 gangliosidosis of the Sandhoff type are presented. A dramatic response of the severe dysesthesias to amitriptyline and gabapentin is described. Symptomatic sensory neuropathy may be a component of late-onset GM2 gangliosidosis. PMID:11483398

  9. Individual Restriction Of Fine Specificity Variability In Anti-GM1 IgG Antibodies Associated With Guillain-Barré Syndrome

    PubMed Central

    Lardone, Ricardo D.; Yuki, Nobuhiro; Irazoqui, Fernando J.; Nores, Gustavo A.

    2016-01-01

    Elevated titers of serum antibodies against GM1 ganglioside are associated with a variety of autoimmune neuropathies. Much evidence indicates these autoantibodies play a primary role in the disease processes, but the mechanism for their appearance is unclear. We studied the fine specificity of anti-GM1 antibodies of the IgG isotype present in sera from patients with Guillain-Barré syndrome (GBS), using thin-layer chromatogram-immunostaining of GM1, asialo-GM1 (GA1), GD1b and GM1-derivatives with small modifications on the oligosaccharide moiety. We were able to distinguish populations of antibodies with different fine specificity. Remarkably, individual patients presented only one or two of them, and different patients had different populations. This restriction in the variability of antibody populations suggests that the appearance of the anti-GM1 antibodies is a random process involving restricted populations of lymphocytes. With the origin of disease-associated anti-GM1 antibodies as a context, this finding could provide explanation for the “host susceptibility factor” observed in GBS following enteritis with GM1 oligosaccharide-carrying strains of Campylobacter jejuni. PMID:26818965

  10. Lo/Ld phase coexistence modulation induced by GM1.

    PubMed

    Puff, Nicolas; Watanabe, Chiho; Seigneuret, Michel; Angelova, Miglena I; Staneva, Galya

    2014-08-01

    Lipid rafts are assumed to undergo biologically important size-modulations from nanorafts to microrafts. Due to the complexity of cellular membranes, model systems become important tools, especially for the investigation of the factors affecting "raft-like" Lo domain size and the search for Lo nanodomains as precursors in Lo microdomain formation. Because lipid compositional change is the primary mechanism by which a cell can alter membrane phase behavior, we studied the effect of the ganglioside GM1 concentration on the Lo/Ld lateral phase separation in PC/SM/Chol/GM1 bilayers. GM1 above 1mol % abolishes the formation of the micrometer-scale Lo domains observed in GUVs. However, the apparently homogeneous phase observed in optical microscopy corresponds in fact, within a certain temperature range, to a Lo/Ld lateral phase separation taking place below the optical resolution. This nanoscale phase separation is revealed by fluorescence spectroscopy, including C12NBD-PC self-quenching and Laurdan GP measurements, and is supported by Gaussian spectral decomposition analysis. The temperature of formation of nanoscale Lo phase domains over an Ld phase is determined, and is shifted to higher values when the GM1 content increases. A "morphological" phase diagram could be made, and it displays three regions corresponding respectively to Lo/Ld micrometric phase separation, Lo/Ld nanometric phase separation, and a homogeneous Ld phase. We therefore show that a lipid only-based mechanism is able to control the existence and the sizes of phase-separated membrane domains. GM1 could act on the line tension, "arresting" domain growth and thereby stabilizing Lo nanodomains. PMID:24835016

  11. [Brown-Vialetto-Van Laere syndrome: a case with anti-ganglioside GM1 antibodies and literature review].

    PubMed

    Sztajzel, R; Kohler, A; Reichart, M; Djientcheu, V P; Chofflon, M; Magistris, M R

    1998-01-01

    We report the case of a woman suffering from progressive bulbopontine paralysis in whose the first symptom, bilateral hypoacousia, began in childhood. This clinical picture is that of the Brown-Vialetto-Van Laere (BVVL) syndrome. Anti-ganglioside GM1 antibodies were moderately elevated in this patient. Intravenous immunoglobulins produced little benefit. The main clinical characteristics of 29 BVVL patients reported in literature are reviewed, and the pathological significance of anti-GM1 antibodies is discussed in the context of this disorder. PMID:9773026

  12. Normally Occurring Human Anti-GM1 Immunoglobulin M Antibodies and the Immune Response to Bacteria

    PubMed Central

    Alaniz, María E.; Lardone, Ricardo D.; Yudowski, Silvia L.; Farace, María I.; Nores, Gustavo A.

    2004-01-01

    Anti-GM1 antibodies of the immunoglobulin M (IgM) isotype are normal components of the antibody repertoire of adult human serum. Using a sensitive high-performance thin-layer chromatography (HPTLC) immunostaining assay, we found that these antibodies were absent in the umbilical vein and children <1 month of age but could be detected after 1 month of age. Although most of the children older than 6 months of age were positive, there were still a few negative children. The appearance of anti-GM1 IgM antibodies showed a perfect concordance with two well-characterized antibacterial antibodies, anti-Forssman and anti-blood group A, which indicates a similar origin. We also studied IgM reactivity with lipopolysaccharides (LPSs) from gram-negative bacteria isolated from stool samples from healthy babies and from Escherichia coli HB101 in serum from individuals of different ages. We found a positive reaction with both LPSs in all the children more than 1 month of age analyzed, even in those that were negative for anti-GM1 antibodies. Anti-GM1 IgM antibodies were purified from adult serum by affinity chromatography and tested for the ability to bind LPSs from different bacteria. This highly specific preparation showed reactivity only with LPS from a strain of Campylobacter jejuni isolated from a patient with diarrhea. We conclude that normally occurring IgM antibodies are generated after birth, probably during the immune defense against specific bacterial strains. PMID:15039337

  13. The physiological effect of anti-GM1 antibodies on saltatory conduction and transmembrane currents in single motor axons.

    PubMed

    Hirota, N; Kaji, R; Bostock, H; Shindo, K; Kawasaki, T; Mizutani, K; Oka, N; Kohara, N; Saida, T; Kimura, J

    1997-12-01

    Anti-ganglioside (anti-GM1) antibodies have been implicated in the pathogenesis of Guillain-Barré syndrome, multifocal motor neuropathy and motor neuron diseases. It has been held that they may interfere with saltatory conduction by blocking sodium channels. We tested this hypothesis by analysing action potentials from 140 single nerve fibres in 22 rat ventral roots using external longitudinal current measurement. High-titre anti-GM1 sera from Guillain-Barré syndrome or multifocal motor neuropathy patients, or anti-GM1 rabbit sera were applied to the rat ventral root, where saltatory conduction in single motor fibres was serially observed for 4-12 h (mean 8.2 h). For control experiments, we also tested anti-galactocerebroside (anti-GalC) sera, which causes acute demyelinative conduction block, and tetrodotoxin (TTX), a sodium channel blocker. Conduction block was found in 82% of the fibres treated with anti-GalC sera and 100% treated with TTX, but only in 2% (one out of 44) treated with the patients' sera and 5% (two out of 38) treated with rabbit anti-GM1 sera. All the nodes blocked by anti-GM1 sera revealed intense passive outward membrane current, in the internode just beyond the last active node. This pattern of current flow was similar to that in fibres blocked by demyelination with anti-GalC sera, and quite different from that seen in fibres blocked by reducing sodium currents with TTX. Our findings suggest that anti-GM1 sera neither mediate conduction block nor block sodium channels on their own. We conclude that physiological action of the antibody alone is insufficient to explain clinically observed conduction block in human diseases. PMID:9448571

  14. GM2 gangliosidosis in British Jacob sheep.

    PubMed

    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

    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

  15. [On the determination of Gm(1) in hard dental tissue (author's transl)].

    PubMed

    Heuschkel, H J; Lieske, W

    1979-01-01

    Tests for the presence of Gm(1) substance were made on a total of 104 human teeth. In about 90 percent of the cases examined, it was possible to observe agreement between the serum and the Gm(1) substance. Lack of eluted dental material and a high degree of affection with caries were found to have adverse effects upon Gm(1) typification. Detection of the Gm(1) substance is another important characteristic in forensic identification. PMID:158914

  16. Clustering effects of GM1 and formation mechanisms of interdigitated liquid disordered domains in GM1/SM/CHOL-supported planar bilayers on mica surfaces

    NASA Astrophysics Data System (ADS)

    Shang, Zhiguo; Mao, Yanli; Tero, Ryugo; Liu, Xinli; Hoshino, Tyuji; Tanaka, Motohiko; Urisu, Tsuneo

    2010-09-01

    We have observed by atomic force microscopy that an interdigitated liquid disordered domain (ILDD) is formed in the ganglioside (GM1)/sphingomyelin (SM)/cholesterol (CHOL) bilayers on a mica surface and accelerates the formation of fibriller Aβ agglomerates. By studies of the mechanisms using molecular dynamics simulations, we conclude that the ILDD structure is formed as a result of the phase separation to SM- and GM1-rich domains on the mica surface induced by the effects of GM1 clustering and the interaction between the GM1 head group and the water layer adsorbed in the ditrigonal cavity on the mica surface.

  17. Substrate reduction therapy in juvenile GM2 gangliosidosis.

    PubMed

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

    2009-01-01

    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+/-4.5 years) received oral miglustat at doses of 100-200mg t.i.d. adjusted to body surface area. Patients underwent general and neurological examinations, neuropsychological, electrophysiological, and brain MRI studies. All patients showed neurological deterioration over the period of the study, with particularly notable worsening of gait, speech and coordination. One patient experienced acute psychosis, and another showed worsening of pre-existing epilepsy. Some neuropsychological tests showed no evidence of deterioration in the three patients with high enough cognitive functioning for reliable assessment. Profound cognitive impairment in two children precluded neuropsychological evaluation. In four patients, evaluation of brain MRI showed no changes in white matter signal abnormalities and cerebellar atrophy noted at baseline, while one patient showed progression of cerebellar and supratentorial brain atrophy. Transmission electron microscopy analysis of peripheral mononuclear cells showed reduction of intracytoplasmatic inclusions with treatment. SRT with miglustat of patients with jGM2g failed to ameliorate progressive neurological deterioration, but apparently no worsening of some areas of cognitive function tested and brain MRI lesions was noted over 24 months of treatment. The results must be interpreted with care owing to the small sample of patients and the lack of a control-arm. PMID:19595619

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

    PubMed

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

    2010-12-01

    GM2 gangliosidosis type Sandhoff is caused by a defect of beta-hexosaminidase, an enzyme involved in the catabolism of gangliosides. It has been proposed that substrate reduction therapy using N-butyl-deoxynojirimycin (miglustat) may delay neurological progression, 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) in a patient with chronic Sandhoff disease manifesting with an atypical, spinal muscular atrophy phenotype. The follow-up included serial neurological examinations, blood tests, abdominal ultrasound, and neurophysiologic, cognitive, brain, and muscle MRI studies. We document some minor effects on neurological progression in chronic Sandhoff disease by miglustat treatment, confirming the necessity of phase II therapeutic trials including early-stage patients in order to assess its putative efficacy in chronic Sandhoff disease. PMID:20821051

  19. Ganglioside GM1 mimicry in Campylobacter strains from sporadic infections in the United States.

    PubMed

    Nachamkin, I; Ung, H; Moran, A P; Yoo, D; Prendergast, M M; Nicholson, M A; Sheikh, K; Ho, T; Asbury, A K; McKhann, G M; Griffin, J W

    1999-05-01

    To determine whether GM1-like epitopes in Campylobacter species are specific to O serotypes associated with Guillain-Barré syndrome (GBS) or whether they are frequent among random Campylobacter isolates causing enteritis, 275 random enteritis-associated isolates of Campylobacter jejuni were analyzed. To determine whether GM1-like epitopes in Campylobacter species are specific to O serotypes associated with Guillan-Barre syndrome (GBS) or whether they are frequent among random Campylobacter isolates causing enteritis, 275 enteritis-associated isolates, randomly collected in the United States, were analyzed using a cholera-toxin binding assay [corrected]. Overall, 26.2% of the isolates were positive for the GM1-like epitope. Of the 36 different O serotypes in the sample, 21 (58.3%) contained no strains positive for GM1, whereas in 6 serotypes (16.7%), >50% of isolates were positive for GM1. GBS-associated serotypes were more likely to contain strains positive for GM1 than were non-GBS-associated serotypes (37.8% vs. 15.1%, P=.0116). The results suggest that humans are frequently exposed to strains exhibiting GM1-like mimicry and, while certain serotypes may be more likely to possess GM1-like epitopes, the presence of GM1-like epitopes on Campylobacter strains does not itself trigger GBS. PMID:10191221

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

    PubMed

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

    2007-03-23

    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

  1. Condensing and Fluidizing Effects of Ganglioside GM1 on Phospholipid Films

    PubMed Central

    Frey, Shelli L.; Chi, Eva Y.; Arratia, Cristóbal; Majewski, Jaroslaw; Kjaer, Kristian; Lee, Ka Yee C.

    2008-01-01

    Mixed monolayers of the ganglioside GM1 and the lipid dipalmitoylphosphatidlycholine (DPPC) at air-water and solid-air interfaces were investigated using various biophysical techniques to ascertain the location and phase behavior of the ganglioside molecules in a mixed membrane. The effects induced by GM1 on the mean molecular area of the binary mixtures and the phase behavior of DPPC were followed for GM1 concentrations ranging from 5 to 70 mol %. Surface pressure isotherms and fluorescence microscopy imaging of domain formation indicate that at low concentrations of GM1 (<25 mol %), the monolayer becomes continually more condensed than DPPC upon further addition of ganglioside. At higher GM1 concentrations (>25 mol %), the mixed monolayer becomes more expanded or fluid-like. After deposition onto a solid substrate, atomic force microscopy imaging of these lipid monolayers showed that GM1 and DPPC pack cooperatively in the condensed phase domain to form geometrically packed complexes that are more ordered than either individual component as evidenced by a more extended total height of the complex arising from a well-packed hydrocarbon tail region. Grazing incidence x-ray diffraction on the DPPC/GM1 binary mixture provides evidence that ordering can emerge when two otherwise fluid components are mixed together. The addition of GM1 to DPPC gives rise to a unit cell that differs from that of a pure DPPC monolayer. To determine the region of the GM1 molecule that interacts with the DPPC molecule and causes condensation and subsequent expansion of the monolayer, surface pressure isotherms were obtained with molecules modeling the backbone or headgroup portions of the GM1 molecule. The observed concentration-dependent condensing and fluidizing effects are specific to the rigid, sugar headgroup portion of the GM1 molecule. PMID:18192361

  2. A pilot study with monosialoganglioside GM1 on acute cerebral ischemia.

    PubMed

    Giraldi, C; Masi, M C; Manetti, M; Carabelli, E; Martini, A

    1990-06-01

    Reported here are the results of an open controlled study on the use of GM1 in cases of ischemic strokes in its acute phase. A statistically significant improvement was observed in cases treated with GM1 for neurological deficits (assessed by Mathew's rating scale, modified by Fritz-Werner) at 21, 60 and 120 days and for disability at 120 days. PMID:2206015

  3. GM1 Ganglioside Inhibits β-Amyloid Oligomerization Induced by Sphingomyelin.

    PubMed

    Amaro, Mariana; Šachl, Radek; Aydogan, Gokcan; Mikhalyov, Ilya I; Vácha, Robert; Hof, Martin

    2016-08-01

    β-Amyloid (Aβ) oligomers are neurotoxic and implicated in Alzheimer's disease. Neuronal plasma membranes may mediate formation of Aβ oligomers in vivo. Membrane components sphingomyelin and GM1 have been shown to promote aggregation of Aβ; however, these studies were performed under extreme, non-physiological conditions. We demonstrate that physiological levels of GM1 , organized in nanodomains do not seed oligomerization of Aβ40 monomers. We show that sphingomyelin triggers oligomerization of Aβ40 and that GM1 is counteractive thus preventing oligomerization. We propose a molecular explanation that is supported by all-atom molecular dynamics simulations. The preventive role of GM1 in the oligomerization of Aβ40 suggests that decreasing levels of GM1 in the brain, for example, due to aging, could reduce protection against Aβ oligomerization and contribute to the onset of Alzheimer's disease. PMID:27295499

  4. Condensing and fluidizing effects of ganglioside GM1 on phospholipid films.

    PubMed

    Frey, Shelli L; Chi, Eva Y; Arratia, Cristóbal; Majewski, Jaroslaw; Kjaer, Kristian; Lee, Ka Yee C

    2008-04-15

    Mixed monolayers of the ganglioside G(M1) and the lipid dipalmitoylphosphatidlycholine (DPPC) at air-water and solid-air interfaces were investigated using various biophysical techniques to ascertain the location and phase behavior of the ganglioside molecules in a mixed membrane. The effects induced by G(M1) on the mean molecular area of the binary mixtures and the phase behavior of DPPC were followed for G(M1) concentrations ranging from 5 to 70 mol %. Surface pressure isotherms and fluorescence microscopy imaging of domain formation indicate that at low concentrations of G(M1) (<25 mol %), the monolayer becomes continually more condensed than DPPC upon further addition of ganglioside. At higher G(M1) concentrations (>25 mol %), the mixed monolayer becomes more expanded or fluid-like. After deposition onto a solid substrate, atomic force microscopy imaging of these lipid monolayers showed that G(M1) and DPPC pack cooperatively in the condensed phase domain to form geometrically packed complexes that are more ordered than either individual component as evidenced by a more extended total height of the complex arising from a well-packed hydrocarbon tail region. Grazing incidence x-ray diffraction on the DPPC/G(M1) binary mixture provides evidence that ordering can emerge when two otherwise fluid components are mixed together. The addition of G(M1) to DPPC gives rise to a unit cell that differs from that of a pure DPPC monolayer. To determine the region of the G(M1) molecule that interacts with the DPPC molecule and causes condensation and subsequent expansion of the monolayer, surface pressure isotherms were obtained with molecules modeling the backbone or headgroup portions of the G(M1) molecule. The observed concentration-dependent condensing and fluidizing effects are specific to the rigid, sugar headgroup portion of the G(M1) molecule. PMID:18192361

  5. GM1 erythroimmunoassay for detection and titration of Escherichia coli heat-labile enterotoxin.

    PubMed

    Germani, Y; Bégaud, E; Guesdon, J L; Moreau, J P

    1986-11-01

    A GM1 ganglioside erythroimmunoassay for the detection of heat-labile Escherichia coli enterotoxin (LT) was developed for use in poorly equipped laboratories in developing countries. This assay is based on the immunological similarity between Vibrio cholerae toxin and LT and uses cholera toxin antiserum and sheep anti-rabbit immunoglobulin covalently coupled to sheep erythrocytes as conjugate. This assay has the following advantages over other currently available techniques: the reagents it uses are stable, in particular, tanned and sensitized sheep erythrocytes; GM1 ganglioside is commercially available; erythro-adsorption can be read with the naked eye; the test can be completed in 1 day; and as little as 4 ng of V. cholerae toxin or LT per ml can be detected accurately. The GM1 ganglioside erythroimmunoassay showed good quantitative and qualitative correlation with the Vero cell assay and the conventional GM1 enzyme-linked immunosorbent assay. The GM1 ganglioside erythroimmunoassay was somewhat less sensitive than the GM1 enzyme-linked immunosorbent assay but more sensitive than the Vero cell assay. Results obtained for 12 LT-positive and 138 LT-negative E. coli strains correlated with results obtained with GM1 enzyme-linked immunosorbent and Vero cell assays. PMID:3533985

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

    PubMed Central

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

    2008-01-01

    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

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

    PubMed

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

    1989-01-01

    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

  8. Decoupling Polarization of the Golgi Apparatus and GM1 in the Plasma Membrane

    PubMed Central

    Bisel, Blaine; Calamai, Martino; Vanzi, Francesco; Pavone, Francesco Saverio

    2013-01-01

    Cell polarization is a process of coordinated cellular rearrangements that prepare the cell for migration. GM1 is synthesized in the Golgi apparatus and localized in membrane microdomains that appear at the leading edge of polarized cells, but the mechanism by which GM1 accumulates asymmetrically is unknown. The Golgi apparatus itself becomes oriented toward the leading edge during cell polarization, which is thought to contribute to plasma membrane asymmetry. Using quantitative image analysis techniques, we measure the extent of polarization of the Golgi apparatus and GM1 in the plasma membrane simultaneously in individual cells subject to a wound assay. We find that GM1 polarization starts just 10 min after stimulation with growth factors, while Golgi apparatus polarization takes 30 min. Drugs that block Golgi polarization or function have no effect on GM1 polarization, and, conversely, inhibiting GM1 polarization does not affect Golgi apparatus polarization. Evaluation of Golgi apparatus and GM1 polarization in single cells reveals no correlation between the two events. Our results indicate that Golgi apparatus and GM1 polarization are controlled by distinct intracellular cascades involving the Ras/Raf/MEK/ERK and the PI3K/Akt/mTOR pathways, respectively. Analysis of cell migration and invasion suggest that MEK/ERK activation is crucial for two dimensional migration, while PI3K activation drives three dimensional invasion, and no cumulative effect is observed from blocking both simultaneously. The independent biochemical control of GM1 polarity by PI3K and Golgi apparatus polarity by MEK/ERK may act synergistically to regulate and reinforce directional selection in cell migration. PMID:24312472

  9. In silico phase separation in the presence of GM1 in ternary and quaternary lipid bilayers.

    PubMed

    Basu, Ipsita; Mukhopadhyay, Chaitali

    2015-07-14

    Cell membranes are multi-component mixtures with structural and compositional heterogeneity exhibiting a complex phase behavior. Domains formed in cell membranes often known as "Rafts" are of immense importance. Using coarse grained molecular dynamics simulations, we have studied the spontaneous phase separation of the ternary (POPC [1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine]/cholesterol/GM1) and quaternary (POPC/PSM[palmitoyl sphingomyelin]/cholesterol/GM1) lipid bilayers into liquid ordered (Lo) and liquid disordered (Ld) domains due to self-aggregation of GM1 molecules and co-localization of cholesterol with GM1 in accordance with experiments. It is found that GM1 molecules have the ability to associate strongly with each other which leads to the formation of ordered domains in the lipid mixture and the interactions are through the head group and unsaturated tails present in GM1. Preference of cholesterol for association with GM1 over PSM is observed, the domains consisting of GM1 and cholesterol are formed even in the presence of PSM. PSM also forms small domains with cholesterol that are randomly distributed in the Ld phase. Estimation of dynamic quantities like diffusion coefficient also shows that cholesterol has the highest diffusion rate in the Ld phase which is further attributed to its flip flop ability. It is found that in the presence of PSM, cholesterol can undergo flip flop even in the Lo phase. This is accredited to the interaction of cholesterol with PSM from which it can be concluded that in the presence of PSM, the domains formed by GM1 are less tightly packed and less stable than that in the ternary mixture. PMID:26067631

  10. Changes in GM1 ganglioside content and localization in cholestatic rat liver.

    PubMed

    Jirkovská, Marie; Majer, Filip; Smídová, Jaroslava; Stríteský, Jan; Shaik, Gouse Mohiddin; Dráber, Petr; Vítek, Libor; Marecek, Zdenek; Smíd, Frantisek

    2007-07-01

    (Glyco)sphingolipids (GSL) are believed to protect the cell against harmful environmental factors by increasing the rigidity of plasma membrane. Marked decrease of membrane fluidity in cholestatic hepatocytes was described but the role of GSL therein has not been investigated so far. In this study, localization in hepatocytes of a representative of GSL, the GM1 ganglioside, was compared between of rats with cholestasis induced by 17alpha-ethinylestradiol (EE) and vehicle propanediol treated or untreated animals. GM1 was monitored by histochemical reaction employing cholera toxin B-subunit. Our findings in normal rat liver tissue showed that GM1 was localized in sinusoidal and canalicular hepatocyte membranes in both peripheral and intermediate zones of the hepatic lobules, and was nearly absent in central zones. On the contrary, in EE-treated animals GM1 was also expressed in central lobular zones. Moreover, detailed densitometry analysis at high magnification showed greater difference of GM1 expression between sinusoidal surface areas and areas of adjacent cytoplasm, caused as well by increased sinusoidal staining in central lobular zone as by decreased staining in cytoplasm in peripheral zone. These differences correlated with serum bile acids as documented by linear regression analyses. Both GM1 content and mRNA corresponding to GM1-synthase remained unchanged in livers; the enhanced expression of GM1 at sinusoidal membrane thus seems to be due to re-distribution of cellular GM1 at limited biosynthesis and could be responsible for protection of hepatocytes against harmful effects of bile acids accumulated during cholestasis. PMID:17333356

  11. Progressive dystonia symptomatic of juvenile GM2 gangliosidosis.

    PubMed

    Nardocci, N; Bertagnolio, B; Rumi, V; Angelini, L

    1992-01-01

    A 9-year-old boy showed a progressive generalized dystonia, with onset at the age of 4 years, combined with mental deterioration and behavioral disturbances. The values of beta-hexosaminidase activities studied in plasma, leukocytes, and fibroblasts obtained using two different substrates (MUG-NAc and MUG-NAc-6-S) were significantly reduced but higher than in Tay-Sachs disease and similar to those found in the juvenile chronic form of GM2 gangliosidosis. With anticholinergic therapy, for 1.5 years, the dystonic symptoms did not progress and the boy can still care for himself and attend school. The description of another case of the disease, clinically expressed as dystonia, corroborates the existence of a dystonic phenotype of GM2 gangliosidosis. PMID:1532632

  12. Recovery from Experimental Parkinsonism in Primates with GM1 Ganglioside Treatment

    NASA Astrophysics Data System (ADS)

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

    1992-05-01

    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.

  13. Animal models of GM2 gangliosidosis: utility and limitations

    PubMed Central

    Lawson, Cheryl A; Martin, Douglas R

    2016-01-01

    GM2 gangliosidosis, a subset of lysosomal storage disorders, is caused by a deficiency of the glycohydrolase, β-N-acetylhexosaminidase, and includes the closely related Tay–Sachs and Sandhoff diseases. The enzyme deficiency prevents the normal, stepwise degradation of ganglioside, which accumulates unchecked within the cellular lysosome, particularly in neurons. As a result, individuals with GM2 gangliosidosis experience progressive neurological diseases including motor deficits, progressive weakness and hypotonia, decreased responsiveness, vision deterioration, and seizures. Mice and cats are well-established animal models for Sandhoff disease, whereas Jacob sheep are the only known laboratory animal model of Tay–Sachs disease to exhibit clinical symptoms. Since the human diseases are relatively rare, animal models are indispensable tools for further study of pathogenesis and for development of potential treatments. Though no effective treatments for gangliosidoses currently exist, animal models have been used to test promising experimental therapies. Herein, the utility and limitations of gangliosidosis animal models and how they have contributed to the development of potential new treatments are described. PMID:27499644

  14. Animal models of GM2 gangliosidosis: utility and limitations.

    PubMed

    Lawson, Cheryl A; Martin, Douglas R

    2016-01-01

    GM2 gangliosidosis, a subset of lysosomal storage disorders, is caused by a deficiency of the glycohydrolase, β-N-acetylhexosaminidase, and includes the closely related Tay-Sachs and Sandhoff diseases. The enzyme deficiency prevents the normal, stepwise degradation of ganglioside, which accumulates unchecked within the cellular lysosome, particularly in neurons. As a result, individuals with GM2 gangliosidosis experience progressive neurological diseases including motor deficits, progressive weakness and hypotonia, decreased responsiveness, vision deterioration, and seizures. Mice and cats are well-established animal models for Sandhoff disease, whereas Jacob sheep are the only known laboratory animal model of Tay-Sachs disease to exhibit clinical symptoms. Since the human diseases are relatively rare, animal models are indispensable tools for further study of pathogenesis and for development of potential treatments. Though no effective treatments for gangliosidoses currently exist, animal models have been used to test promising experimental therapies. Herein, the utility and limitations of gangliosidosis animal models and how they have contributed to the development of potential new treatments are described. PMID:27499644

  15. Insights into the behavioral difference of water in the presence of GM1.

    PubMed

    Basu, Ipsita; Manna, Moutusi; Mukhopadhyay, Chaitali

    2015-12-21

    Studies on the structure and dynamics of interfacial water, emphasizing on the properties of water near the surface of biomolecules, are well reported, but there is a lack of evidence on the behavior of water near a comparatively rough surface containing molecules with a bulky head group like GM1. In this report we comparatively analyze the structure and dynamics of water as a function of distance from the lipid head group in GM1 containing lipid bilayers, with the lipid bilayers where GM1 is not present. This approach effectively demonstrates the behavioral difference and hence delayed convergence from bound water to bulk water in the presence of GM1 compared to a relatively smooth surface. PMID:26611347

  16. GM1 monosialoganglioside pretreatment protects against soman-induced seizure-related brain damage.

    PubMed

    Ballough, G P; Cann, F J; Smith, C D; Forster, J S; Kling, C E; Filbert, M G

    1998-05-01

    The effects of GM1 monosialoganglioside pretreatment on brain damage resulting from soman-induced seizure activity were examined in this study. Male Sprague-Dawley rats were infused with GM1 via an osmotic minipump connected through a permanent cannula implanted intracerebroventricularly and challenged with soman (83 micrograms/kg, i.e., 1.25 x LD50) 4 d after initiation of GM1 infusion. Electrocorticographic recordings were monitored via indwelling cortical electrodes. Twenty-seven hours after soman administration, anesthetized rats were euthanized via transcardial perfusion with buffered paraformaldehyde. Brains were processed for hematoxylin and eosin (H&E), cresyl violet (CV), and acetylcholinesterase (AChE) histochemistry, and glial fibrillary acidic protein (GFAP) and microtubule-associated protein 2 (MAP2) immunohistochemistry. All soman-challenged rats not infused with GM1 (n = 14) developed status epilepticus (SE). PMID:9778643

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

    PubMed Central

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

    2009-01-01

    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

  18. Galleria mellonella native and analogue peptides Gm1 and ΔGm1. II) anti-bacterial and anti-endotoxic effects.

    PubMed

    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

    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 ΔGm1, 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-α (TNF-α) 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 ΔGm1, 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 100μg/ml, making them suitable as new anti-infective agents. PMID:25016054

  19. Galleria mellonella native and analogue peptides Gm1 and ΔGm1. I) biophysical characterization of the interaction mechanisms with bacterial model membranes.

    PubMed

    Correa, Wilmar; Manrique-Moreno, Marcela; Patiño, Edwin; Peláez-Jaramillo, Carlos; Kaconis, Yani; Gutsmann, Thomas; Garidel, Patrick; Heinbockel, Lena; Brandenburg, Klaus

    2014-10-01

    Natural occurring antimicrobial peptides (AMPs) are important components of the innate immune system of animals and plants. They are considered to be promising alternatives to conventional antibiotics. Here we present a comparative study of two synthetic peptides: Gm1, corresponding to the natural overall uncharged peptide from Galleria mellonella (Gm) and ΔGm1, a modified overall positively charged Gm1 variant. We have studied the interaction of the peptides with lipid membranes composed of different kinds of lipopolysaccharides (LPS) and dimyristoylphosphatidylglycerol (DMPG), in some cases also dimyristoylphosphatidylethanolamine (DMPE) as representative lipid components of Gram-negative bacterial membranes, by applying Fourier-transform infrared spectroscopy (FTIR), Förster resonance energy transfer spectroscopy (FRET), differential scanning calorimetry (DSC) and isothermal titration calorimetry (ITC). Gm1 generates a destabilizing effect on the gel to liquid crystalline phase transition of the acyl chains of the lipids, as deduced from a decrease in the phase transition temperature and enthalpy, suggesting a fluidization, whereas ΔGm1 led to the opposite behavior. Further, FTIR analysis of the functional groups of the lipids participating in the interaction with the peptides indicated a shift in the band position and intensity of the asymmetric PO2(-) stretching vibration originating from the lipid phosphate groups, a consequence of the sterical changes in the head group region. Interestingly, FRET spectroscopy showed a similar intercalation of both peptides into the DMPG and LPS, but much less into the DMPE membrane systems. These results are discussed in the light of a possible use of the peptides as antimicrobial and anti-endotoxin drugs. PMID:25017800

  20. Complement Factor H and Simian Virus 40 bind the GM1 ganglioside in distinct conformations.

    PubMed

    Blaum, Bärbel S; Frank, Martin; Walker, Ross C; Neu, Ursula; Stehle, Thilo

    2016-05-01

    Mammalian cell surfaces are decorated with a variety of glycan chains that orchestrate development and defense and are exploited by pathogens for cellular attachment and entry. While glycosidic linkages are, in principle, flexible, the conformational space that a given glycan can sample is subject to spatial and electrostatic restrictions imposed by its overall chemical structure. Here, we show how the glycan moiety of the GM1 ganglioside, a branched, monosialylated pentasaccharide that serves as a ligand for various proteins, undergoes differential conformational selection in its interactions with different lectins. Using STD NMR and X-ray crystallography, we found that the innate immune regulator complement Factor H (FH) binds a previously not reported GM1 conformation that is not compatible with the GM1-binding sites of other structurally characterized GM1-binding lectins such as the Simian Virus 40 (SV40) capsid. Molecular dynamics simulations of the free glycan in explicit solvent on the 10 μs timescale reveal that the FH-bound conformation nevertheless corresponds to a minimum in the Gibbs free energy plot. In contrast to the GM1 conformation recognized by SV40, the FH-bound GM1 conformation is associated with poor NOE restraints, explaining how it escaped(1)H-(1)H NOE-restrained modeling in the past and highlighting the necessity for ensemble representations of glycan structures. PMID:26715202

  1. GM1 ganglioside reverses the cognitive deficits induced by MK801 in mice.

    PubMed

    Ni, Yu-Fei; Zhang, Wei; Bao, Xiao-Feng; Wang, Wei; Song, Lu; Jiang, Bo

    2016-08-01

    Cognitive deficits are core symptoms of schizophrenia, but effective treatments are still lacking. Previous studies have reported that the brain-derived neurotrophic factor (BDNF) signaling is closely involved in learning and memory. Monosialotetrahexosylganglioside (GM1) is a ganglioside with wide-ranging pharmacologic effects that enhances the BDNF signaling cascade. This study aimed to assess the effects of GM1 on schizophrenia-related cognitive impairments. A brief disruption of N-methyl-D-aspartate receptors with MK801 was used to generate the animal model for cognitive deficits in schizophrenia. It was found that MK801-treated mice showed significant deficits in memory ability compared with control mice in different behavior tests, and this was accompanied by decreased hippocampal BDNF signaling pathway. Consecutive administration of GM1 fully restored the MK801-induced cognitive deficits and the impaired BDNF signaling in the hippocampus. Furthermore, a BDNF system inhibitor abolished the effects of GM1 in the MK801 model. Taken together, our results show that GM1 could reverse the MK801-induced cognitive deficits, suggesting a potential usefulness of GM1 in treating the schizophrenia-related cognitive impairments. PMID:26960162

  2. Post-partum psychosis in adult GM2 gangliosidosis. A case report.

    PubMed

    Lichtenberg, P; Navon, R; Wertman, E; Dasberg, H; Lerer, B

    1988-09-01

    Adult hexosaminidase A deficiency is a form of GM2 gangliosidosis with autosomal recessive inheritance. Only 35 cases (mostly among Ashkenazic Jews) have been reported worldwide. Symptoms include, in a third of the cases, psychosis. A 27-year-old sufferer with no prior psychiatric history, developed a post-partum psychosis, with affective and hebephrenic components, 3 days following her first delivery. She responded to lithium within 10 days of initiating treatment; the full episode lasted 1 month. We conclude that lithium is the preferred treatment for psychosis in such adult patients, especially in light of possible long-term neurological deterioration caused by phenothiazines. Ashkenazic Jews with atypical neurological syndromes presenting with psychosis should be tested for hexosaminidase A deficiency. PMID:2977954

  3. Neuropathology of chronic GM2 gangliosidosis due to hexosaminidase A deficiency.

    PubMed

    Kornfeld, M

    2008-01-01

    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

  4. Interaction of Treponema denticola TD-4, GM-1, and MS25 with human gingival fibroblasts.

    PubMed Central

    Weinberg, A; Holt, S C

    1990-01-01

    The adherence of Treponema denticola GM-1, TD-4, and MS25 to human gingival fibroblasts (HGFs) was studied to serve as an introduction to investigations into the interactions of these oral bacteria with human host cells. Under both aerobic (5% CO2) and anaerobic (85% N2 plus 10% H2 plus 5% CO2) environments, the interactions with the HGFs were such that strains GM-1 and MS25 were consistently more adherent than strain TD-4. Polyclonal antibodies to GM-1 inhibited GM-1 adherence by 70%, while MS25 and TD-4 showed differing degrees of cross-reactive inhibition, indicative of common but not identical epitopes on the surface of the three T. denticola strains. Pretreatment of the three strains with trypsin did not inhibit adherence; proteinase K did, however, inhibit this interaction by 80%. Trypsin pretreatment of the HGFs resulted in increases in adherence of 50 and 86% for GM-1 and MS25, respectively, while a decrease of 41% was noted for TD-4. Exposure of the T. denticola strains to sugars and lectin pretreatment of the HGFs implicated adherence mediation by mannose and galactose residues on the HGF surface. Periodate treatment of HGFs resulted in a 50% drop in adherence for GM-1 and MS25, but did not decrease that of TD-4. Addition of fetal bovine serum inhibited adherence of the three strains to differing degrees, with TD-4 being the most susceptible. Addition of purified fibronectin (100 micrograms/ml) resulted in greater than 50% inhibition in GM-1 and MS25 adherence, while a 25% increase occurred with TD-4. While strain differences were noted in some of the parameters studied, the results indicate two possibilities for T. denticola-HGF adherence: a lectinlike adhesin(s) on the T. denticola surface with affinity for galactose and mannose on the HGF surface, and a serum host factor(s) bridging T. denticola and HGFs. Images PMID:2160430

  5. GM1 Ganglioside in Parkinson’s Disease: Pilot Study of Effects on Dopamine Transporter Binding

    PubMed Central

    Schneider, Jay S.; Cambi, Franca; Gollomp, Stephen M.; Kuwabara, Hiroto; Brašić, James R.; Leiby, Benjamin; Sendek, Stephanie; Wong, Dean F.

    2015-01-01

    Objective GM1 ganglioside has been suggested as a treatment for Parkinson’s disease (PD), potentially having symptomatic and disease modifying effects. The current pilot imaging study was performed to examine effects of GM1 on dopamine transporter binding, as a surrogate measure of disease progression, studied longitudinally. Methods Positron emission tomography (PET) imaging data were obtained from a subset of subjects enrolled in a delayed start clinical trial of GM1 in PD1: 15 Early-start (ES) subjects, 14 Delayed-start (DS) subjects, and 11 Comparison (standard-of-care) subjects. Treatment subjects were studied over a 2.5 year period while Comparison subjects were studied over 2 years. Dynamic PET scans were performed over 90 minutes following injection of [11C]methylphenidate. Regional values of binding potential (BPND) were analyzed for several striatal volumes of interest. Results Clinical results for this subset of subjects were similar to those previously reported for the larger study group. ES subjects showed early symptomatic improvement and slow symptom progression over the study period. DS and Comparison subjects were initially on the same symptom progression trajectory but diverged once DS subjects received GM1 treatment. Imaging results showed significant slowing of BPND loss in several striatal regions in GM1-treated subjects and in some cases, an increased BPND in some striatal regions was detected after GM1 use. Interpretation Results of this pilot imaging study provide additional data to suggest a potential disease modifying effect of GM1 on PD. These results need to be confirmed in a larger number of subjects. PMID:26099170

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

    SciTech Connect

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

    2010-04-09

    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.

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

    PubMed

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

    2010-04-01

    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 approximately 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. PMID:20206128

  8. Protection against Experimental Stroke by Ganglioside GM1 Is Associated with the Inhibition of Autophagy

    PubMed Central

    Li, Li; Tian, Jinghua; Long, Mitchell King-Wei; Chen, Yong; Lu, Jianfei; Zhou, Changman; Wang, Tianlong

    2016-01-01

    Ganglioside GM1, which is particularly abundant in the central nervous system (CNS), is closely associated with the protection against several CNS disorders. However, controversial findings have been reported on the role of GM1 following ischemic stroke. In the present study, using a rat middle cerebral artery occlusion (MCAO) model, we investigated whether GM1 can protect against ischemic brain injury and whether it targets the autophagy pathway. GM1 was delivered to Sprague-Dawley male rats at 3 doses (25 mg/kg, 50 mg/kg, 100 mg/kg) by intraperitoneal injection soon after reperfusion and then once daily for 2 days. The same volume of saline was given as a control. Tat–Beclin-1, a specific autophagy inducer, was administered by intraperitoneal injection at 24 and 48 hours post-MCAO. Infarction volume, mortality and neurological function were assessed at 72 hours after ischemic insult. Immunofluorescence and Western blotting were performed to determine the expression of autophagy-related proteins P62, LC3 and Beclin-1 in the penumbra area. No significant changes in mortality and physiological variables (heart rate, blood glucose levels and arterial blood gases) were observed between the different groups. However, MCAO resulted in enhanced conversion of LC3-I into LC3-II, P62 degradation, high levels of Beclin-1, a large area infarction (26.3±3.6%) and serious neurobehavioral deficits. GM1 (50 mg/kg) treatment significantly reduced the autophagy activation, neurobehavioral dysfunctions, and infarction volume (from 26.3% to 19.5%) without causing significant adverse side effects. However, this biological function could be abolished by Tat–Beclin-1. In conclusion: GM1 demonstrated safe and robust neuroprotective effects that are associated with the inhibition of autophagy following experimental stroke. PMID:26751695

  9. [Recent advances in molecular genetics of GM2 gangliosidosis].

    PubMed

    Wakamatsu, N

    1995-12-01

    Recent advances in molecular genetics of GM2 gangliosidosis are reviewed. GM2 gangliosidosis is an autosomal recessive, neurodegenerative disease caused by a deficiency of beta-hexosaminidase (Hex, EC 3.2.1.52) A activity, resulting in accumulation of GM2 ganglioside in the lysosomes of neuronal cells. There are two catalytically active forms of this enzyme: Hex A, composed of one alpha and one beta subunits. Three forms of this disease, Tay-Sachs disease, Sandhoff disease, and GM2 activator deficiency, have been recognized according to whether the defect involves the alpha subunit, beta subunit, or GM2 activator protein, respectively. A number of gene abnormalities responsible for the disease have been identified and mutations specific for phenotypes and racial backgrounds are summarized. Recently, the murine models of human Tay-Sachs disease and Sandhoff disease have been produced. With the finding of dramatically clinical phenotypes in these mice, these models could be useful for research on the pathogenesis or therapy of these diseases. PMID:8577047

  10. Pathology of GM2 gangliosidosis in Jacob sheep.

    PubMed

    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

    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

  11. The Research of Improved Grey GM (1, 1) Model to Predict the Postprandial Glucose in Type 2 Diabetes

    PubMed Central

    Wang, Yannian; Wei, Fenfen; Sun, Changqing; Li, Quanzhong

    2016-01-01

    Diabetes may result in some complications and increase the risk of many serious health problems. The purpose of clinical treatment is to carefully manage the blood glucose concentration. If the blood glucose concentration is predicted, treatments can be taken in advance to reduce the harm to patients. For this purpose, an improved grey GM (1, 1) model is applied to predict blood glucose with a small amount of data, and especially in terms of improved smoothness it can get higher prediction accuracy. The original data of blood glucose of type 2 diabetes is acquired by CGMS. Then the prediction model is established. Finally, 50 cases of blood glucose from the Henan Province People's Hospital are predicted in 5, 10, 15, 20, 25, and 30 minutes, respectively, in advance to verify the prediction model. The prediction result of blood glucose is evaluated by the EGA, MSE, and MAE. Particularly, the prediction results of postprandial blood glucose are presented and analyzed. The result shows that the improved grey GM (1, 1) model has excellent performance in postprandial blood glucose prediction. PMID:27314034

  12. GM1 Ganglioside Treatment Facilitates Behavioral Recovery from Bilateral Brain Damage

    NASA Astrophysics Data System (ADS)

    Sabel, Bernhard A.; Slavin, Mary D.; Stein, Donald G.

    1984-07-01

    Adult rats with bilateral lesions of the caudate nucleus were treated with GM1 ganglioside. Although animals injected with a control solution were severely impaired in their ability to learn a complex spatial task, those treated with ganglioside were able to learn spatial reversals.

  13. GM1 induces p38 and microtubule dependent ramification of rat primary microglia in vitro.

    PubMed

    Park, Ji-Young; Kim, Hee Young; Jou, Ilo; Park, Sang Myun

    2008-12-01

    Microglia are immunologically competent cells in the central nervous system and considered to be a key player in brain inflammation. The morphological change of microglia has been shown to be linked to functional phenotypes both in vivo and in vitro. As an attempt to identify factors that regulate microglial morphology, we investigated the effect of gangliosides on microglial ramification in vitro. Brain gangliosides mixture and GM1 induced typical ramification of cultured rat primary microglia, however, GD1a and GT1b did not. Although GM1 significantly induced the expression of neurotrophin-3 (NT-3), NT-3 did not induce typical morphological changes in cultured rat primary microglia. SB203580 (an inhibitor of p38), and paclitaxel and nocodazole (microtubule-disrupting drugs) inhibited GM1-induced microglial ramification, but Jaki (an inhibitor of JAK), PD98059 (an inhibitor of Erk1/2), SP600125 (an inhibitor of JNK), and cytochalasin B and latrunculin B (actin polymerization inhibitors) did not, suggesting that GM1 induced ramification of microglia in p38- and microtubule-dependent manner. This in vitro system would be helpful in understanding the mechanisms of microglial ramification and physiological roles of gangliosides in microglia. PMID:18930716

  14. GM1 Ganglioside is Involved in Epigenetic Activation Loci of Neuronal Cells.

    PubMed

    Tsai, Yi-Tzang; Itokazu, Yutaka; Yu, Robert K

    2016-02-01

    Gangliosides are sialic acid-containing glycosphingolipids that are most abundant in the nerve tissues. The quantity and expression pattern of gangliosides in brain change drastically throughout development and are mainly regulated through stage-specific expression of glycosyltransferase (ganglioside synthase) genes. We previously demonstrated that acetylation of histones H3 and H4 on the N-acetylgalactosaminyltransferase I (GalNAcT, GA2/GM2/GD2/GT2-synthase) gene promoter resulted in recruitment of trans-activation factors. In addition, we reported that epigenetic activation of the GalNAcT gene was also detected as accompanied by an apparent induction of neuronal differentiation in neural stem cells responding to an exogenous supplement of ganglioside GM1. Here, we present evidence supporting the concept that nuclear GM1 is associated with gene regulation in neuronal cells. We found that nuclear GM1 binds acetylated histones on the promoters of the GalNAcT and NeuroD1 genes in differentiated neurons. Our study demonstrates for the first time that GM1 interacts with chromatin via acetylated histones at the nuclear periphery of neuronal cells. PMID:26498762

  15. GLTP mediated non-vesicular GM1 transport between native membranes.

    PubMed

    Lauria, Ines; van Üüm, Jan; Mjumjunov-Crncevic, Esmina; Walrafen, David; Spitta, Luis; Thiele, Christoph; Lang, Thorsten

    2013-01-01

    Lipid transfer proteins (LTPs) are emerging as key players in lipid homeostasis by mediating non-vesicular transport steps between two membrane surfaces. Little is known about the driving force that governs the direction of transport in cells. Using the soluble LTP glycolipid transfer protein (GLTP), we examined GM1 (monosialotetrahexosyl-ganglioside) transfer to native membrane surfaces. With artificial GM1 donor liposomes, GLTP can be used to increase glycolipid levels over natural levels in either side of the membrane leaflet, i.e., external or cytosolic. In a system with native donor- and acceptor-membranes, we find that GLTP balances highly variable GM1 concentrations in a population of membranes from one cell type, and in addition, transfers lipids between membranes from different cell types. Glycolipid transport is highly efficient, independent of cofactors, solely driven by the chemical potential of GM1 and not discriminating between the extra- and intracellular membrane leaflet. We conclude that GLTP mediated non-vesicular lipid trafficking between native membranes is driven by simple thermodynamic principles and that for intracellular transport less than 1 µM GLTP would be required in the cytosol. Furthermore, the data demonstrates the suitability of GLTP as a tool for artificially increasing glycolipid levels in cellular membranes. PMID:23555818

  16. Interaction of liposomes composed of phospholipids, GM1 ganglioside and cholesterol with human keratinocytes in culture.

    PubMed

    Pitto, M; Palestini, P; Ferraretto, A; Marazzi, M; Donati, V; Falcone, L; Masserini, M

    1999-04-01

    We studied the possibility of supplementing human keratinocytes with exogenous lipids (phospholipids, sphingolipids and cholesterol) and evaluated their influence on cell proliferation, using cells cultured in vitro. Experiments carried out with liposomes composed of cholesterol/GM1 ganglioside and different phospholipids (5:1.5:10, M/M/M), showed that liposomes associated with cells more efficiently when they contained soya lecithin. The treatment with liposomes made of the ternary mixture did not modify the rate of cell proliferation, as assessed by the incorporation of [3H]-thymidine. In contrast, the proliferation rate strongly decreased (65% with respect to the control) using the same liposomes without GM1. Experiments carried out with GM1 alone showed a strong stimulation of the proliferation rate (144% with respect to the control). Fluorescence dequenching experiments, carried out with the probe octadecyl rhodamine B chloride, showed that fusion was the main mechanism of liposome-cell interaction. Metabolic studies established that exogenously administered GM1--either embedded in liposomes or as a pure glycolipid dispersion--led to the production of several products, including ceramide. Altogether, these results show that different, opposing effects can be exerted on cell proliferation by the administration of lipids, separately or in mixtures, to human keratinocytes, and indicate the importance of a correct formulation for supplementing human keratinocytes with exogenous lipids. PMID:10335921

  17. Characterization of Chromium Waste Form Based on Biocementation by Microbacterium sp. GM-1.

    PubMed

    Lun, Limei; Li, Dongwei; Yin, Yajie; Li, Dou; Xu, Guojing; Zhao, Ziqiang; Li, Shan

    2016-09-01

    This paper demonstrated a biocementation technology for chromium slag by strain GM-1, a calcifying ureolytic bacterium identified as Microbacterium, based on microbially induced calcium carbonate. The characterization of Microbacterium sp. GM-1 was assessed to know the growth curve in different concentrations of Cr(VI). Microbacterium sp. GM-1 was tolerant to a concentration of 120 mg/L Cr(VI). Chromium waste forms were prepared using chromium, sand, soil and bacterial culture. There we had three quality ratios (8:2:1; 8:1:1; 8:2:0.5) of material (chromium, sand and soil, respectively). Bacterial and control chromium waste forms were analyzed by thermal gravimetric analyzer. All bacterial forms (8:2:1; 8:1:1; 8:2:0.5 J) showed sharp weight loss near the decomposition temperature of calcium carbonate between 600 and 700 °C. It indicated that the efficient bacterial strain GM-1 had induced calcium carbonate precipitate during bioremediation process. A five step Cr(VI) sequential extraction was performed to evaluate its distribution pattern in chromium waste forms. The percentage of Cr(VI) was found to significantly be decreased in the exchangeable fraction of chromium waste forms and subsequently, that was markedly increased in carbonated fraction after biocementation by GM-1. Further, compressive strength test and leaching test were carried out. The results showed that chromium waste forms after biocementation had higher compressive strength and lower leaching toxicity. Additionally, the samples made of 8:1:1 (m/m/m) chromium + sand + soil were found to develop the highest compressive strength and stand the lowest concentration of Cr(VI) released into the environment. PMID:27407300

  18. Fucosyl-GM1a, an endoglycoceramidase-resistant ganglioside of porcine brain.

    PubMed

    Xu, Xu; Monjusho, Hatsumi; Inagaki, Masanori; Hama, Yoichiro; Yamaguchi, Kuniko; Sakaguchi, Keishi; Iwamori, Masao; Okino, Nozomu; Ito, Makoto

    2007-01-01

    The use of bovine brain has been prohibited in many countries because of the world-wide prevalence of mad cow disease, and thus porcine brain is expected to be a new source for the preparation of gangliosides. Here, we report the presence of a ganglioside in porcine brain which is strongly resistant to hydrolysis by endoglycoceramidase, an enzyme capable of cleaving the glycosidic linkage between oligosaccharides and ceramides of various glycosphingolipids. Five major gangliosides (designated PBG-1, 2, 3, 4, 5) were extracted from porcine brain by Folch's partition, followed by mild alkaline hydrolysis and PBA column chromatography. We found that PBG-2, but not the others, was strongly resistant to hydrolysis by the enzyme. After the purification of PBG-2 with Q-Sepharose, Silica gel 60 and Prosep-PB chromatographies, the structure of PBG-2 was determined by GC, GC-MS, FAB-MS and NMR spectroscopy as Fucalpha1-2Galbeta1-3GalNAcbeta1-4(NeuAcalpha2-3)Galbeta1-4Glcbeta1-1'Cer (fucosyl-GM1a). The ceramide was mainly composed of C18:0 and C20:0 fatty acids and d18:1 and d20:1 sphingoid bases. The apparent kcat/Km for fucosyl-GM1a was found to be 30 times lower than that for GM1a, indicating that terminal fucosylation makes GM1a resistant to hydrolysis by the enzyme. This report indicates the usefulness of endoglycoceramidase to prepare fucosyl-GM1a from porcine brain. PMID:17167042

  19. Colocalization of the ganglioside G(M1) and cholesterol detected by secondary ion mass spectrometry.

    PubMed

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

    2013-04-17

    The characterization of the lateral organization of components in biological membranes and the evolution of this arrangement in response to external triggers remain 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 microscale 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 colocalization 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 μm); (3) nanometer-scale domains (d = 100 nm to 1 μm) 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

  20. GM1-Modified Lipoprotein-like Nanoparticle: Multifunctional Nanoplatform for the Combination Therapy of Alzheimer's Disease.

    PubMed

    Huang, Meng; Hu, Meng; Song, Qingxiang; Song, Huahua; Huang, Jialin; Gu, Xiao; Wang, Xiaolin; Chen, Jun; Kang, Ting; Feng, Xingye; Jiang, Di; Zheng, Gang; Chen, Hongzhuan; Gao, Xiaoling

    2015-11-24

    Alzheimer's disease (AD) exerts a heavy health burden for modern society and has a complicated pathological background. The accumulation of extracellular β-amyloid (Aβ) is crucial in AD pathogenesis, and Aβ-initiated secondary pathological processes could independently lead to neuronal degeneration and pathogenesis in AD. Thus, the development of combination therapeutics that can not only accelerate Aβ clearance but also simultaneously protect neurons or inhibit other subsequent pathological cascade represents a promising strategy for AD intervention. Here, we designed a nanostructure, monosialotetrahexosylganglioside (GM1)-modified reconstituted high density lipoprotein (GM1-rHDL), that possesses antibody-like high binding affinity to Aβ, facilitates Aβ degradation by microglia, and Aβ efflux across the blood-brain barrier (BBB), displays high brain biodistribution efficiency following intranasal administration, and simultaneously allows the efficient loading of a neuroprotective peptide, NAP, as a nanoparticulate drug delivery system for the combination therapy of AD. The resulting multifunctional nanostructure, αNAP-GM1-rHDL, was found to be able to protect neurons from Aβ(1-42) oligomer/glutamic acid-induced cell toxicity better than GM1-rHDL in vitro and reduced Aβ deposition, ameliorated neurologic changes, and rescued memory loss more efficiently than both αNAP solution and GM1-rHDL in AD model mice following intranasal administration with no observable cytotoxicity noted. Taken together, this work presents direct experimental evidence of the rational design of a biomimetic nanostructure to serve as a safe and efficient multifunctional nanoplatform for the combination therapy of AD. PMID:26440073

  1. [Adult GM2 gangliosidosis: improvement of ataxia with GABAergic drugs].

    PubMed

    Gazulla Abío, J; Benavente Aguilar, I

    2002-03-01

    The authors present a case of adult GM2 gangliosidosis, B1 enzymatic type. The main clinical features found were cerebellar ataxia, proximal lower limb weakness and myokymia. The neurological examination, and the biochemical, electrophysiologic and imaging studies are all described. Decreased activity of the enzyme beta-hexosaminidase A in the metabolism of the sulfate substrate 4-MU-NAGS was found in serum. Global cerebellar atrophy was observed in a cranial nuclear magnetic resonance. The electrophysiologic study showed continuous spontaneous activity integrated by myokymia and neuromyotonic discharges in addition to signs of acute and chronic denervation. Disappearance of the myokymia and improvement in the ataxia were attained with the use of the GABAergic drugs gabapentin and tiagabine. The authors try to explain the clinical improvement obtained with the drugs by relating their mechanisms of action to the central nervous system neurotransmitter alterations proposed for this disease. PMID:11927106

  2. Synthesis and aggregative properties of GM1 ganglioside (IV3Neu5AcGgOse4Cer) containing D-(+)-2-hydroxystearic acid.

    PubMed

    Sonnino, S; Acquotti, D; Cantu, L; Chigorno, V; Valsecchi, M; Casellato, R; Masserini, M; Corti, M; Allevi, P; Tettamanti, G

    1994-02-01

    GM1 ganglioside containing a hydroxylated fatty acid moiety, GM1(OH), was synthesized starting from lyso-GM1 and D-(+)-2-hydroxystearic acid. The aggregative, geometrical and distribution properties of GM1(OH) were compared with those of stearic acid containing GM1 ganglioside; laser light scattering measurements, differential scanning calorimetry and fluorescence spectroscopy were used. GM1 and GM1(OH) are present in solution as micelles with a hydrodynamic radius of 58.7 and 60.0 A, and molecular mass of 470 and 570 kDa, respectively. The surface area occupied by the monomer of GM1(OH) at the lipid-water interface of the aggregate was calculated to be 117 A2, which is 3 A2 lower than that determined for GM1. Proton NMR analyses of GM1 and GM1(OH) suggest different three-dimensional structures at the ganglioside lipid-water interface. Both GM1(OH) and GM1 inserted into dipalmitoylphosphatidylcholine (DPPC) vesicles undergo segregation phenomena, with the formation of ganglioside-enriched microdomains, but GM1(OH) shows a higher degree of dispersion in the DPPC matrix and exerts a lower rigidifying effect than does GM1. PMID:8181107

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

    NASA Astrophysics Data System (ADS)

    Tabaszewski, Maciej; Cempel, Czeslaw

    2015-02-01

    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.

  4. Interaction between Simian Virus 40 Major Capsid Protein VP1 and Cell Surface Ganglioside GM1 Triggers Vacuole Formation

    PubMed Central

    Luo, Yong; Motamedi, Nasim; Magaldi, Thomas G.; Gee, Gretchen V.; Atwood, Walter J.

    2016-01-01

    ABSTRACT Simian virus 40 (SV40), a polyomavirus that has served as an important model to understand many aspects of biology, induces dramatic cytoplasmic vacuolization late during productive infection of monkey host cells. Although this activity led to the discovery of the virus in 1960, the mechanism of vacuolization is still not known. Pentamers of the major SV40 capsid protein VP1 bind to the ganglioside GM1, which serves as the cellular receptor for the virus. In this report, we show that binding of VP1 to cell surface GM1 plays a key role in SV40 infection-induced vacuolization. We previously showed that SV40 VP1 mutants defective for GM1 binding fail to induce vacuolization, even though they replicate efficiently. Here, we show that interfering with GM1-VP1 binding by knockdown of GM1 after infection is established abrogates vacuolization by wild-type SV40. Vacuole formation during permissive infection requires efficient virus release, and conditioned medium harvested late during SV40 infection rapidly induces vacuoles in a VP1- and GM1-dependent fashion. Furthermore, vacuolization can also be induced by a nonreplicating SV40 pseudovirus in a GM1-dependent manner, and a mutation in BK pseudovirus VP1 that generates GM1 binding confers vacuole-inducing activity. Vacuolization can also be triggered by purified pentamers of wild-type SV40 VP1, but not by GM1 binding-defective pentamers or by intracellular expression of VP1. These results demonstrate that SV40 infection-induced vacuolization is caused by the binding of released progeny viruses to GM1, thereby identifying the molecular trigger for the activity that led to the discovery of SV40. PMID:27006465

  5. Multi-scale molecular dynamics study of cholera pentamer binding to a GM1-phospholipid membrane.

    PubMed

    Sridhar, Akshay; Kumar, Amit; Dasmahapatra, Ashok Kumar

    2016-07-01

    The AB5 type toxin produced by the Vibrio cholerae bacterium is the causative agent of the cholera disease. The cholera toxin (CT) has been shown to bind specifically to GM1 glycolipids on the membrane surface. This binding of CT to the membrane is the initial step in its endocytosis and has been postulated to cause significant disruption to the membrane structure. In this work, we have carried out a combination of coarse-grain and atomistic simulations to study the binding of CT to a membrane modelled as an asymmetrical GM1-DPPC bilayer. Simulation results indicate that the toxin binds to the membrane through only three of its five B subunits, in effect resulting in a tilted bound configuration. Additionally, the binding of the CT can increase the area per lipid of GM1 leaflet, which in turn can cause the membrane regions interacting with the bound subunits to experience significant bilayer thinning and lipid tail disorder across both the leaflets. PMID:27474868

  6. PYRIMETHAMINE AS A POTENTIAL PHARMACOLOGICAL CHAPERONE FOR LATE-ONSET FORMS OF GM2 GANGLIOSIDOSIS

    PubMed Central

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

    2007-01-01

    Late-onset GM2-gangliosidosis (GM2) is composed of two related, autosomal recessive, neurodegenerative diseases, both resulting from deficiency of lysosomal, heterodimeric β-hexosaminidase A (Hex A, αβ). 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 ER. To date all successful PCs have also been competitive inhibitors. Screening for Hex A inhibitors in a library of 1040 FDA-approved compounds identified pyrimethamine (PYR) as the most potent inhibitor. Cell lines from 10 late-onset Tay-Sachs (11 α-mutations, 2 novel), and 7 Sandhoff (9 β-mutations, 4 novel) disease patients, were cultured with PYR at concentrations corresponding to therapeutic doses. Cells carrying the most common late-onset mutation, αG269S, showed significant increases in residual Hex A activity, as did all 7 of the β-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 α-subunit. PYR, which binds to the active site in domain II, was able to function as PC even to domain I β-mutants. We concluded that PYR functions as a mutation-specific PC, variably enhancing residual lysosomal Hex A levels in late-onset GM2 patient cells. PMID:17237499

  7. [A case of multifocal motor neuropathy with IgM lambda anti-GM1 antibody and IgM kappa paraprotein reacting exclusively with GM2].

    PubMed

    Arai, Motomi; Kusunoki, Susumu

    2009-01-01

    A 57-year-old previously healthy woman visited our clinic complaining of frequent muscle cramps and progressive weakness in the hands and fingers for 3 years. On examination, cranial nerves were unremarkable. There were moderate weakness and mild muscle wasting with fasciculation in the left thumb flexor and interossei on both sides. Tendon reflexes were hypoactive. There were no pathologic reflexes or sensory deficit. The cerebrospinal fluid was unremarkable. Nerve conduction studies demonstrated conduction block in the right ulnar nerve. Compound muscle action potential in the left median nerve was low-normal. Distal motor latencies, motor and sensory nerve conduction velocities were normal in all nerves tested. A diagnosis of multifocal motor neuropathy was made. Two courses of intravenous immunoglobulin infusion gave no beneficial effects. The patient had IgM kappa monoclonal gammopathy of undetermined significance. Her serum IgM reacted with GM2, GM1, and GA1 but not with GD1a, GD1b, GD3, GalNAc-GD1a, GT1b, GQ1b, galactocerebroside, or sulfated glucuronyl paragloboside. IgM kappa paraprotein reacted exclusively with GM2. Only IgM lambda bound to GM1 and GA1, suggesting the possibility that another paraprotein, though undetectable by immunoelectrohoresis, had a reactivity with GM1 and GA1. This case showed previously unreported antigenic specificity of paraproteins in cases of MMN. PMID:19348179

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

    PubMed Central

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

    2007-01-01

    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

  9. Mutations in the GM1 Binding Site of Simian Virus 40 VP1 Alter Receptor Usage and Cell Tropism

    PubMed Central

    Magaldi, Thomas G.; Buch, Michael H. C.; Murata, Haruhiko; Erickson, Kimberly D.; Neu, Ursula; Garcea, Robert L.; Peden, Keith; Stehle, Thilo

    2012-01-01

    Polyomaviruses are nonenveloped viruses with capsids composed primarily of 72 pentamers of the viral VP1 protein, which forms the outer shell of the capsid and binds to cell surface oligosaccharide receptors. Highly conserved VP1 proteins from closely related polyomaviruses recognize different oligosaccharides. To determine whether amino acid changes restricted to the oligosaccharide binding site are sufficient to determine receptor specificity and how changes in receptor usage affect tropism, we studied the primate polyomavirus simian virus 40 (SV40), which uses the ganglioside GM1 as a receptor that mediates cell binding and entry. Here, we used two sequential genetic screens to isolate and characterize viable SV40 mutants with mutations in the VP1 GM1 binding site. Two of these mutants were completely resistant to GM1 neutralization, were no longer stimulated by incorporation of GM1 into cell membranes, and were unable to bind to GM1 on the cell surface. In addition, these mutant viruses displayed an infection defect in monkey cells with high levels of cell surface GM1. Interestingly, one mutant infected cells with low cell surface GM1 more efficiently than wild-type virus, apparently by utilizing a different ganglioside receptor. Our results indicate that a small number of mutations in the GM1 binding site are sufficient to alter ganglioside usage and change tropism, and they suggest that VP1 divergence is driven primarily by a requirement to accommodate specific receptors. In addition, our results suggest that GM1 binding is required for vacuole formation in permissive monkey CV-1 cells. Further study of these mutants will provide new insight into polyomavirus entry, pathogenesis, and evolution. PMID:22514351

  10. Juvenile GM2 gangliosidosis (AMB variant): inability to activate hexosaminidase A by activator protein.

    PubMed Central

    Inui, K; Grebner, E E; Jackson, L G; Wenger, D A

    1983-01-01

    Two sibling from a consanguineous Puerto Rican marriage were found to have a juvenile-onset type of lipidosis first noted at age 2 1/2 by expressing difficulties with motor function and developmental delay. They continued to deteriorate, showing muscle atrophy, spasticity, and loss of speech, and death occurred at ages 7 and 8. Examination of the brains from these patients revealed that the concentration of GM2 ganglioside was about 56% of the total gangliosides. Hexosaminidase and percent hexosaminidase A (HEX A) and other lysosomal enzymes were normal in cultured skin fibroblasts, liver, and brain. The concentration of the activator protein required for the enzymatic hydrolysis of GM2 ganglioside was in high normal levels in the brain of the patient available. However, the HEX A from the patient's brain and liver as well as from skin fibroblast lysates could not be activated to hydrolyze GM2 ganglioside by the activator protein from a control or himself. The HEX A from a control could be activated by the activator protein from controls or this patient. These patients appear to have a defect in HEX A, which does not affect it heat stability, electrophoretic migration, and activity toward fluorogenic substrates, but may affect the binding of the activator protein required for GM2 ganglioside hydrolysis. We propose to call these patients the AMB variant of GM2 gangliosidosis to denote the mutation in HEX A but with normal levels of HEX A and B with synthetic substrates. This is to distinguish these patients from those missing the activator protein and normal HEX A and B levels. Images Fig. 1 Fig. 2 PMID:6224417

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

    PubMed Central

    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

    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

  12. Application of Grey Model GM(1, 1) to Ultra Short-Term Predictions of Universal Time

    NASA Astrophysics Data System (ADS)

    Lei, Yu; Guo, Min; Zhao, Danning; Cai, Hongbing; Hu, Dandan

    2016-03-01

    A mathematical model known as one-order one-variable grey differential equation model GM(1, 1) has been herein employed successfully for the ultra short-term (<10days) predictions of universal time (UT1-UTC). The results of predictions are analyzed and compared with those obtained by other methods. It is shown that the accuracy of the predictions is comparable with that obtained by other prediction methods. The proposed method is able to yield an exact prediction even though only a few observations are provided. Hence it is very valuable in the case of a small size dataset since traditional methods, e.g., least-squares (LS) extrapolation, require longer data span to make a good forecast. In addition, these results can be obtained without making any assumption about an original dataset, and thus is of high reliability. Another advantage is that the developed method is easy to use. All these reveal a great potential of the GM(1, 1) model for UT1-UTC predictions.

  13. The morphology of GM1 x/SM 0.6-x/Chol 0.4 planar bilayers supported on SiO 2 surfaces

    NASA Astrophysics Data System (ADS)

    Mao, Yanli; Tero, Ryugo; Imai, Yosuke; Hoshino, Tyuji; Urisu, Tsuneo

    2008-07-01

    Ganglioside GM1 (GM1), sphingomyelin (SM) and cholesterol (Chol) are dominant lipid components of rafts in plasma membranes. The morphology of GM1 x/SM 0.6-x/Chol 0.4 SPBs on SiO 2 surfaces has been studied by atomic force microscopy and fluorescence microscopy at various ratios of GM1/SM ( x = 0-0.25). The unique changes in morphology depending on the GM1 concentrations are qualitatively explained by hydrogen bonding and the hydrophobic interactions between SM and Chol, and by hydrogen bonding and the steric effects between bulky GM1 headgroups under Ca 2+ existing conditions and the electrostatic repulsion between the negative charges of GM1 headgroups under Ca 2+ nonexisting conditions.

  14. Improving the detection of IgM antibodies against glycolipids complexes of GM1 and Galactocerebroside in Multifocal Motor Neuropathy using glycoarray and ELISA assays.

    PubMed

    Delmont, Emilien; Halstead, Susan; Galban-Horcajo, Francesc; Yao, Denggao; Desnuelle, Claude; Willison, Hugh

    2015-01-15

    Antibodies against complexes of GM1:GalC are detected in multifocal motor neuropathy. Previous studies used different techniques, explaining disparities in the results. Antibodies against GM1 and GM1:GalC with different proportions of GalC were measured with both glycoarray and ELISA in 20 multifocal motor neuropathies, and 45 controls. The 1:5 ratio and the 1:1 ratio of GM1:GalC (weight ratio) were respectively the most effective for glycoarray and for ELISA. Testing for anti-GM1:GalC antibodies increased the sensitivity from 40% with anti-GM1 antibodies to 65% with array and 60% with ELISA without loss in specificity (above 91%). Anti-GM1:GalC antibodies are effective biological tools to diagnose multifocal motor neuropathy. PMID:25468269

  15. The Natural History of Juvenile or Subacute GM2 Gangliosidosis: 21 New Cases and Literature Review of 134 Previously Reported

    PubMed Central

    Maegawa, Gustavo H. B.; Stockley, Tracy; Tropak, Michael; Banwell, Brenda; Blaser, Susan; Kok, Fernando; Giugliani, Roberto; Mahuran, Don; Clarke, Joe T. R.

    2010-01-01

    OBJECTIVE Juvenile GM2 gangliosidosis is a group of inherited neurodegenerative diseases caused by deficiency of lysosomal β-hexosaminidase resulting in GM2 ganglioside accumulation in brain. The purpose of this study was to delineate the natural history of the condition and identify genotype-phenotype correlations that might be helpful in predicting the course of the disease in individual patients. METHODS A cohort of 21 patients with juvenile GM2 gangliosidosis, 15 with the Tay-Sachs variant and 6 with the Sandhoff variant, was studied prospectively in 2 centers. Our experience was compared with previously published reports on 134 patients. Information about clinical features, β-hexosaminidase enzyme activity, and mutation analysis was collected. RESULTS In our cohort of patients, the mean (±SD) age of onset of symptoms was 5.3 ± 4.1 years, with a mean follow-up time of 8.4 years. The most common symptoms at onset were gait disturbances (66.7%), incoordination (52.4%), speech problems (28.6%), and developmental delay (28.6%). The age of onset of gait disturbances was 7.1 ± 5.6 years. The mean time for progression to becoming wheelchair-bound was 6.2 ± 5.5 years. The mean age of onset of speech problems was 7.0 ± 5.6 years, with a mean time of progression to anarthria of 5.6 ± 5.3 years. Muscle wasting (10.6 ± 7.4 years), proximal weakness (11.1 ± 7.7 years), and incontinence of sphincters (14.6 ± 9.7 years) appeared later in the course of the disease. Psychiatric disturbances and neuropathy were more prevalent in patients with the Sandhoff variant than in those with the Tay-Sachs variant. However, dysphagia, sphincter incontinence, and sleep problems occurred earlier in those with the Tay-Sachs variant. Cerebellar atrophy was the most common finding on brain MRI (52.9%). The median survival time among the studied and reviewed patients was 14.5 years. The genotype-phenotype correlation revealed that in patients with the Tay-Sachs variant, the presence

  16. Synthesis of reference standards to enable single cell metabolomic studies of tetramethylrhodamine-labelled ganglioside GM1

    PubMed Central

    Larsson, E. Andreas; Olsson, Ulf; Whitmore, Colin; Martins, Rita; Tettamanti, Guido; Schnaar, Ronald L.; Dovichi, Norman J.; Palcic, Monica M.; Hindsgaul, Ole

    2007-01-01

    Ganglioside GM1 and its seven potential catabolic products: asialo-GM1, GM2, asialo-GM2, GM3, Lac-Cer, Glc-Cer and Cer, were labelled with tetramethylrhodamine (TMR) to permit ultra-sensitive analysis using laser-induced fluorescence (LIF) detection. The preparation involved acylation of the homogenous C18 lyso-forms of GM1, Lac-Cer, Glc-Cer and Cer with the N-hydroxysuccinimide ester of a β-alanine-tethered 6-TMR derivative, followed by conversion of these labelled products using galactosidase, sialidase and sialyltransferase enzymes. The TMR-glycolipd analogs produced are detectable on TLC down to the 1 ng level by naked eye. All 8 compounds could be separated in under 4 minutes in capillary electrophoresis where they could be detected at the zeptomole (ca 1000 molecule) level using LIF. PMID:17069778

  17. GM1 cluster mediates formation of toxic Aβ fibrils by providing hydrophobic environments.

    PubMed

    Fukunaga, Saori; Ueno, Hiroshi; Yamaguchi, Takahiro; Yano, Yoshiaki; Hoshino, Masaru; Matsuzaki, Katsumi

    2012-10-16

    The conversion of soluble, nontoxic amyloid β-proteins (Aβ) to aggregated, toxic forms rich in β-sheets is considered to be a key step in the development of Alzheimer's disease. Accumulating evidence suggests that lipid-protein interactions play a crucial role in the aggregation of amyloidogenic proteins like Aβ. Our group has previously reported that amyloid fibrils of Aβ formed on membranes containing clusters of GM1 ganglioside (M-fibrils) exhibit greater cytotoxicity than fibrils formed in aqueous solution (W-fibrils) [ Okada ( 2008 ) J. Mol. Biol. 382 , 1066 - 1074 ]. W-fibrils are considered to consist of in-register parallel β-sheets. However, the precise molecular structure of M-fibrils and force driving the formation of toxic fibrils remain unclear. In this study, we hypothesized that low-polarity environments provided by GM1 clusters drive the formation of toxic fibrils and compared the structure and cytotoxicity of W-fibrils, M-fibrils, and aggregates formed in a low-polarity solution mimicking membrane environments. First, we determined solvent conditions which mimic the polarity of raftlike membranes using Aβ-(1-40) labeled with the 7-diethylaminocoumarin-3-carbonyl dye. The polarity of a mixture of 80% 1,4-dioxane and 20% water (v/v) was found to be close to that of raftlike membranes. Aβ-(1-40) formed amyloid fibrils within several hours in 80% dioxane (D-fibrils) or in the presence of raftlike membranes, whereas a much longer incubation time was required for fibril formation in a conventional buffer. D-fibrils were morphologically similar to M-fibrils. Fourier-transform infrared spectroscopy suggested that M-fibrils and D-fibrils contained antiparallel β-sheets. These fibrils had greater surface hydrophobicity and exhibited significant toxicity against human neuroblastoma SH-SY5Y cells, whereas W-fibrils with less surface hydrophobicity were not cytotoxic. We concluded that ganglioside clusters mediate the formation of toxic amyloid fibrils

  18. Increased Expression of GM1 Detected by Electrospray Mass Spectrometry in Rat Primary Embryonic Cortical Neurons Exposed to Glutamate Toxicity.

    PubMed

    Park, Dae Hee; Wang, Lynn; Pittock, Paula; Lajoie, Gilles; Whitehead, Shawn Narain

    2016-08-01

    Neurons within different brain regions have varying levels of vulnerability to external stress and respond differently to injury. A potential reason to explain this may lie within a key lipid class of the cell's plasma membrane called gangliosides. These glycosphingolipid species have been shown to play various roles in the maintenance of neuronal viability. The purpose of this study is to use electrospray ionization mass spectrometry (ESI-MS) and immunohistochemistry to evaluate the temporal expression profiles of gangliosides during the course of neurodegeneration in rat primary cortical neurons exposed to glutamate toxicity. Primary embryonic (E18) rat cortical neurons were cultured to DIV (days in vitro) 14. Glutamate toxicity was induced for 1, 3, 6, and 24 h to injure and kill neurons. Immunofluorescence was used to stain for GM1 and GM3 species, and ESI-MS was used to quantify the ganglioside species expressed within these injured neurons. ESI-MS data revealed that GM1, GM2, and GM3 were up-regulated in neurons exposed to glutamate. Interestingly, using immunofluorescence, we demonstrated that the GM1 increase following glutamate exposure occurred in viable neurons, possibly indicating a potential intrinsic neuroprotective response. To test this potential neuroprotective property, neurons were pretreated with GM1 for 24 h prior to glutamate exposure. Pretreatment with GM1 conferred significant neuroprotection against glutamate-induced cell death. Overall, work from this study validates the use of ESI-MS for cell-derived gangliosides and supports the further development of lipid based strategies to protect against neuron cell death. PMID:27376483

  19. Clostridium perfringens Alpha-Toxin Induces Gm1a Clustering and Trka Phosphorylation in the Host Cell Membrane.

    PubMed

    Takagishi, Teruhisa; Oda, Masataka; Kabura, Michiko; Kurosawa, Mie; Tominaga, Kaori; Urano, Shiori; Ueda, Yoshibumi; Kobayashi, Keiko; Kobayashi, Toshihide; Sakurai, Jun; Terao, Yutaka; Nagahama, Masahiro

    2015-01-01

    Clostridium perfringens alpha-toxin elicits various immune responses such as the release of cytokines, chemokines, and superoxide via the GM1a/TrkA complex. Alpha-toxin possesses phospholipase C (PLC) hydrolytic activity that contributes to signal transduction in the pathogenesis of gas gangrene. Little is known about the relationship between lipid metabolism and TrkA activation by alpha-toxin. Using live-cell fluorescence microscopy, we monitored transbilayer movement of diacylglycerol (DAG) with the yellow fluorescent protein-tagged C1AB domain of protein kinase C-γ (EYFP-C1AB). DAG accumulated at the marginal region of the plasma membrane in alpha toxin-treated A549 cells, which also exhibited GM1a clustering and TrkA phosphorylation. Annexin V binding assays showed that alpha-toxin induced the exposure of phosphatidylserine on the outer leaflet of the plasma membrane. However, H148G, a variant toxin which binds cell membrane and has no enzymatic activity, did not induce DAG translocation, GM1a clustering, or TrkA phosphorylation. Alpha-toxin also specifically activated endogenous phospholipase Cγ-1 (PLCγ-1), a TrkA adaptor protein, via phosphorylation. U73122, an endogenous PLC inhibitor, and siRNA for PLCγ-1 inhibited the formation of DAG and release of IL-8. GM1a accumulation and TrkA phosphorylation in A549 cells treated with alpha-toxin were also inhibited by U73122. These results suggest that the flip-flop motion of hydrophobic lipids such as DAG leads to the accumulation of GM1a and TrkA. We conclude that the formation of DAG by alpha-toxin itself (first step) and activation of endogenous PLCγ-1 (second step) leads to alterations in membrane dynamics, followed by strong phosphorylation of TrkA. PMID:25910247

  20. Effects of ganglioside G(M1) and erythropoietin on spinal cord lesions in rats: functional and histological evaluations

    PubMed Central

    Marcon, Raphael Martus; Cristante, Alexandre Fogaça; de Barros Filho, Tarcísio Eloy Pessoa; Ferreira, Ricardo; dos Santos, Gustavo Bispo

    2016-01-01

    OBJECTIVE: To evaluate the functional and histological effects of ganglioside G(M1) and erythropoietin after experimental spinal cord contusion injury. METHODS: Fifty male Wistar rats underwent experimental spinal cord lesioning using an NYU-Impactor device and were randomly divided into the following groups, which received treatment intraperitoneally. The G(M1) group received ganglioside G(M1) (30 mg/kg); the erythropoietin group received erythropoietin (1000 IU/kg); the combined group received both drugs; and the saline group received saline (0.9%) as a control. A fifth group was the laminectomy group, in which the animals were subjected to laminectomy alone, without spinal lesioning or treatment. The animals were evaluated according to the Basso, Beattie and Bresnahan (BBB) scale, motor evoked potential recordings and, after euthanasia, histological analysis of spinal cord tissue. RESULTS: The erythropoietin group had higher BBB scores than the G(M1) group. The combined group had the highest BBB scores, and the saline group had the lowest BBB scores. No significant difference in latency was observed between the three groups that underwent spinal cord lesioning and intervention. However, the combined group showed a significantly higher signal amplitude than the other treatment groups or the saline group (p<0.01). Histological tissue analysis showed no significant difference between the groups. Axonal index was significantly enhanced in the combined group than any other intervention (p<0.01). CONCLUSION: G(M1) and erythropoietin exert therapeutic effects on axonal regeneration and electrophysiological and motor functions in rats subjected to experimental spinal cord lesioning and administering these two substances in combination potentiates their effects. PMID:27438570

  1. Clostridium perfringens Alpha-Toxin Induces Gm1a Clustering and Trka Phosphorylation in the Host Cell Membrane

    PubMed Central

    Takagishi, Teruhisa; Oda, Masataka; Kabura, Michiko; Kurosawa, Mie; Tominaga, Kaori; Urano, Shiori; Ueda, Yoshibumi; Kobayashi, Keiko; Kobayashi, Toshihide; Sakurai, Jun; Terao, Yutaka; Nagahama, Masahiro

    2015-01-01

    Clostridium perfringens alpha-toxin elicits various immune responses such as the release of cytokines, chemokines, and superoxide via the GM1a/TrkA complex. Alpha-toxin possesses phospholipase C (PLC) hydrolytic activity that contributes to signal transduction in the pathogenesis of gas gangrene. Little is known about the relationship between lipid metabolism and TrkA activation by alpha-toxin. Using live-cell fluorescence microscopy, we monitored transbilayer movement of diacylglycerol (DAG) with the yellow fluorescent protein-tagged C1AB domain of protein kinase C-γ (EYFP-C1AB). DAG accumulated at the marginal region of the plasma membrane in alpha toxin-treated A549 cells, which also exhibited GM1a clustering and TrkA phosphorylation. Annexin V binding assays showed that alpha-toxin induced the exposure of phosphatidylserine on the outer leaflet of the plasma membrane. However, H148G, a variant toxin which binds cell membrane and has no enzymatic activity, did not induce DAG translocation, GM1a clustering, or TrkA phosphorylation. Alpha-toxin also specifically activated endogenous phospholipase Cγ-1 (PLCγ-1), a TrkA adaptor protein, via phosphorylation. U73122, an endogenous PLC inhibitor, and siRNA for PLCγ-1 inhibited the formation of DAG and release of IL-8. GM1a accumulation and TrkA phosphorylation in A549 cells treated with alpha-toxin were also inhibited by U73122. These results suggest that the flip-flop motion of hydrophobic lipids such as DAG leads to the accumulation of GM1a and TrkA. We conclude that the formation of DAG by alpha-toxin itself (first step) and activation of endogenous PLCγ-1 (second step) leads to alterations in membrane dynamics, followed by strong phosphorylation of TrkA. PMID:25910247

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

    PubMed

    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

    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

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

    PubMed Central

    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

    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

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

    SciTech Connect

    Wallis, C.; Rezazadeh, S.M.; Forster, M.J.; Lal, H. )

    1992-02-26

    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.

  5. Induction of antibody to asialo GM1 by spermatozoa and its occurrence in the sera of homosexual men with the acquired immune deficiency syndrome (AIDS).

    PubMed Central

    Witkin, S S; Sonnabend, J; Richards, J M; Purtilo, D T

    1983-01-01

    Compared to healthy homosexual and heterosexual men, homosexual men with acquired immune deficiency syndrome (AIDS) possessed significantly higher levels of IgG antibody to the neutral glycolipid asialo GM1 (ganglio-N-tetraosylceramide) (P less than 0.01). Of 31 homosexuals with AIDS, 36% possessed levels of this antibody that were at least two standard deviations above the mean of the healthy men. Furthermore, asialo GM1 antibody could be removed from serum by adsorption with spermatozoa. Weekly rectal insemination of male rabbits with rabbit semen also led to the appearance of antibody to asialo GM1 by 15 weeks. These results suggest that asialo GM1 is a component of ejaculated spermatozoa and demonstrate that rectal insemination by itself can lead to the production of antibodies to this glycolipid in the rabbit. In addition, asialo GM1 antibodies may be of value as a serological marker for the early detection of individuals with AIDS. PMID:6652964

  6. Biochemical characterization of the interactions between doxorubicin and lipidic GM1 micelles with or without paclitaxel loading.

    PubMed

    Leonhard, Victoria; Alasino, Roxana V; Bianco, Ismael D; Garro, Ariel G; Heredia, Valeria; Beltramo, Dante M

    2015-01-01

    Doxorubicin (Dox) is an anthracycline anticancer drug with high water solubility, whose use is limited primarily due to significant side effects. In this study it is shown that Dox interacts with monosialoglycosphingolipid (GM1) ganglioside micelles primarily through hydrophobic interactions independent of pH and ionic strength. In addition, Dox can be incorporated even into GM1 micelles already containing highly hydrophobic paclitaxel (Ptx). However, it was not possible to incorporate Ptx into Dox-containing GM1 micelles, suggesting that Dox could be occupying a more external position in the micelles. This result is in agreement with a higher hydrolysis of Dox than of Ptx when micelles were incubated at alkaline pH. The loading of Dox into GM1 micelles was observed over a broad range of temperature (4°C-55°C). Furthermore, Dox-loaded micelles were stable in aqueous solutions exhibiting no aggregation or precipitation for up to 2 months when kept at 4°C-25°C and even after freeze-thawing cycles. Upon exposure to blood components, Dox-containing micelles were observed to interact with human serum albumin. However, the amount of human serum albumin that ended up being associated to the micelles was inversely related to the amount of Dox, suggesting that both could share their binding sites. In vitro studies on Hep2 cells showed that the cellular uptake and cytotoxic activity of Dox and Ptx from the micellar complexes were similar to those of the free form of these drugs, even when the micelle was covered with albumin. These results support the idea of the existence of different nano-domains in a single micelle and the fact that this micellar model could be used as a platform for loading and delivering hydrophobic and hydrophilic active pharmaceutical ingredients. PMID:26005348

  7. Biochemical characterization of the interactions between doxorubicin and lipidic GM1 micelles with or without paclitaxel loading

    PubMed Central

    Leonhard, Victoria; Alasino, Roxana V; Bianco, Ismael D; Garro, Ariel G; Heredia, Valeria; Beltramo, Dante M

    2015-01-01

    Doxorubicin (Dox) is an anthracycline anticancer drug with high water solubility, whose use is limited primarily due to significant side effects. In this study it is shown that Dox interacts with monosialoglycosphingolipid (GM1) ganglioside micelles primarily through hydrophobic interactions independent of pH and ionic strength. In addition, Dox can be incorporated even into GM1 micelles already containing highly hydrophobic paclitaxel (Ptx). However, it was not possible to incorporate Ptx into Dox-containing GM1 micelles, suggesting that Dox could be occupying a more external position in the micelles. This result is in agreement with a higher hydrolysis of Dox than of Ptx when micelles were incubated at alkaline pH. The loading of Dox into GM1 micelles was observed over a broad range of temperature (4°C–55°C). Furthermore, Dox-loaded micelles were stable in aqueous solutions exhibiting no aggregation or precipitation for up to 2 months when kept at 4°C–25°C and even after freeze–thawing cycles. Upon exposure to blood components, Dox-containing micelles were observed to interact with human serum albumin. However, the amount of human serum albumin that ended up being associated to the micelles was inversely related to the amount of Dox, suggesting that both could share their binding sites. In vitro studies on Hep2 cells showed that the cellular uptake and cytotoxic activity of Dox and Ptx from the micellar complexes were similar to those of the free form of these drugs, even when the micelle was covered with albumin. These results support the idea of the existence of different nano-domains in a single micelle and the fact that this micellar model could be used as a platform for loading and delivering hydrophobic and hydrophilic active pharmaceutical ingredients. PMID:26005348

  8. Binding Cooperativity Matters: A GM1-Like Ganglioside-Cholera Toxin B Subunit Binding Study Using a Nanocube-Based Lipid Bilayer Array.

    PubMed

    Worstell, Nolan C; Krishnan, Pratik; Weatherston, Joshua D; Wu, Hung-Jen

    2016-01-01

    Protein-glycan recognition is often mediated by multivalent binding. These multivalent bindings can be further complicated by cooperative interactions between glycans and individual glycan binding subunits. Here we have demonstrated a nanocube-based lipid bilayer array capable of quantitatively elucidating binding dissociation constants, maximum binding capacity, and binding cooperativity in a high-throughput format. Taking cholera toxin B subunit (CTB) as a model cooperativity system, we studied both GM1 and GM1-like gangliosides binding to CTB. We confirmed the previously observed CTB-GM1 positive cooperativity. Surprisingly, we demonstrated fucosyl-GM1 has approximately 7 times higher CTB binding capacity than GM1. In order to explain this phenomenon, we hypothesized that the reduced binding cooperativity of fucosyl-GM1 caused the increased binding capacity. This was unintuitive, as GM1 exhibited higher binding avidity (16 times lower dissociation constant). We confirmed the hypothesis using a theoretical stepwise binding model of CTB. Moreover, by taking a mixture of fucosyl-GM1 and GM2, we observed the mild binding avidity fucosyl-GM1 activated GM2 receptors enhancing the binding capacity of the lipid bilayer surface. This was unexpected as GM2 receptors have negligible binding avidity in pure GM2 bilayers. These unexpected discoveries demonstrate the importance of binding cooperativity in multivalent binding mechanisms. Thus, quantitative analysis of multivalent protein-glycan interactions in heterogeneous glycan systems is of critical importance. Our user-friendly, robust, and high-throughput nanocube-based lipid bilayer array offers an attractive method for dissecting these complex mechanisms. PMID:27070150

  9. Binding Cooperativity Matters: A GM1-Like Ganglioside-Cholera Toxin B Subunit Binding Study Using a Nanocube-Based Lipid Bilayer Array

    PubMed Central

    Weatherston, Joshua D.

    2016-01-01

    Protein-glycan recognition is often mediated by multivalent binding. These multivalent bindings can be further complicated by cooperative interactions between glycans and individual glycan binding subunits. Here we have demonstrated a nanocube-based lipid bilayer array capable of quantitatively elucidating binding dissociation constants, maximum binding capacity, and binding cooperativity in a high-throughput format. Taking cholera toxin B subunit (CTB) as a model cooperativity system, we studied both GM1 and GM1-like gangliosides binding to CTB. We confirmed the previously observed CTB-GM1 positive cooperativity. Surprisingly, we demonstrated fucosyl-GM1 has approximately 7 times higher CTB binding capacity than GM1. In order to explain this phenomenon, we hypothesized that the reduced binding cooperativity of fucosyl-GM1 caused the increased binding capacity. This was unintuitive, as GM1 exhibited higher binding avidity (16 times lower dissociation constant). We confirmed the hypothesis using a theoretical stepwise binding model of CTB. Moreover, by taking a mixture of fucosyl-GM1 and GM2, we observed the mild binding avidity fucosyl-GM1 activated GM2 receptors enhancing the binding capacity of the lipid bilayer surface. This was unexpected as GM2 receptors have negligible binding avidity in pure GM2 bilayers. These unexpected discoveries demonstrate the importance of binding cooperativity in multivalent binding mechanisms. Thus, quantitative analysis of multivalent protein-glycan interactions in heterogeneous glycan systems is of critical importance. Our user-friendly, robust, and high-throughput nanocube-based lipid bilayer array offers an attractive method for dissecting these complex mechanisms. PMID:27070150

  10. Comparison of two GM1-erythrocyte assays to detect heat-labile Escherichia coli enterotoxin in stool specimens.

    PubMed

    Germani, Y; Guesdon, J L; Phalente, L; Begaud, E; Moreau, J P

    1988-05-01

    Two erythrocyte immunoassay techniques to detect the presence of Escherichia coli heat-labile enterotoxin (LTh) in stool supernatants and cell-free culture supernatants were compared. In the competitive assay, GM1 ganglioside was coated onto V-shaped-well microdilution plates and enterotoxin was coupled to sheep erythrocytes. As little as 0.8 ng of LTh per ml was detected by this method, which was based on the competition between the LTh of the test sample and the sensitized erythrocytes. The second assay made use of chimera antibody prepared by coupling polyclonal anti-LTh antibody to a monoclonal antibody specific for sheep erythrocytes. In this case, LTh, which was specifically bound to a GM1 ganglioside-coated plate, was detected by successively adding the chimera antibody and sheep erythrocytes. The limit of detection of the chimera antibody erythrocyte immunoassay was 0.2 ng/ml. Stool samples were collected from 167 infants hospitalized for diarrhea in the hospital of Noumea, New Caledonia. False-negative reactions due to proteases present in the stool samples were avoided by the addition of phenylmethylsulfonyl fluoride. PMID:3290242

  11. Differential Anatomical Expression of Ganglioside GM1 Species Containing d18:1 or d20:1 Sphingosine Detected by MALDI Imaging Mass Spectrometry in Mature Rat Brain

    PubMed Central

    Weishaupt, Nina; Caughlin, Sarah; Yeung, Ken K.-C.; Whitehead, Shawn N.

    2015-01-01

    GM1 ganglioside plays a role in essential neuronal processes, including differentiation, survival, and signaling. Yet, little is known about GM1 species with different sphingosine bases, such as the most abundant species containing 18 carbon atoms in the sphingosine chain (GM1d18:1), and the less abundant containing 20 carbon atoms (GM1d20:1). While absent in the early fetal brain, GM1d20:1 continues to increase throughout pre- and postnatal development and into old age, raising questions about the functional relevance of the GM1d18:1 to GM1d20:1 ratio. Matrix-assisted laser desorption/ionization imaging mass spectrometry is a novel technology that allows differentiation between these two GM1 species and quantification of their expression within an anatomical context. Using this technology, we find GM1d18:1/d20:1 expression ratios are highly specific to defined anatomical brain regions in adult rats. Thus, the ratio was significantly different among different thalamic nuclei and between the corpus callosum and internal capsule. Differential GM1d18:1/GM1d20:1 ratios measured in hippocampal subregions in rat brain complement previous studies conducted in mice. Across layers of the sensory cortex, opposing expression gradients were found for GM1d18:1 and GM1d20:1. Superficial layers demonstrated lower GM1d18:1 and higher GM1d20:1 signal than other layers, while in deep layers GM1d18:1 expression was relatively high and GM1d20:1 expression low. By far the highest GM1d18:1/d20:1 ratio was found in the amygdala. Differential expression of GM1 with d18:1- or d20:1-sphingosine bases in the adult rat brain suggests tight regulation of expression and points toward a distinct functional relevance for each of these GM1 species in neuronal processes. PMID:26648849

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

    PubMed Central

    Manna, Moutusi; Mukhopadhyay, Chaitali

    2013-01-01

    Interactions of amyloid-β (Aβ) with neuronal membrane are associated with the progression of Alzheimer’s disease (AD). Ganglioside GM1 has been shown to promote the structural conversion of Aβ 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 Aβ monomer and dimers in GM1-containing raft-like membrane. The oligosaccharide head-group of GM1 was observed to act as scaffold for Aβ-binding through sugar-specific interactions. Starting from the initial helical peptide conformation, a β-hairpin motif was formed at the C-terminus of the GM1-bound Aβ-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 Aβ-dimers, the β-structure was further enhanced by peptide-peptide interactions, which might influence the propensity of Aβ 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 Aβ-GM1 and Aβ-Aβ interactions and demonstrate their importance in the early-stages of GM1-mediated Aβ-oligomerisation on membrane surface. PMID:23951128

  13. Late onset GM2 gangliosidosis mimicking spinal muscular atrophy.

    PubMed

    Jamrozik, Z; Lugowska, A; Gołębiowski, M; Królicki, L; Mączewska, J; Kuźma-Kozakiewicz, M

    2013-09-25

    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

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

    PubMed

    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

    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

  15. Binding of CFA/I Pili of Enterotoxigenic Escherichia coli to Asialo-GM1 Is Mediated by the Minor Pilin CfaE.

    PubMed

    Madhavan, T P Vipin; Riches, James D; Scanlon, Martin J; Ulett, Glen C; Sakellaris, Harry

    2016-05-01

    CFA/I pili are representatives of a large family of related pili that mediate the adherence of enterotoxigenic Escherichia coli to intestinal epithelial cells. They are assembled via the alternate chaperone-usher pathway and consist of two subunits, CfaB, which makes up the pilus shaft and a single pilus tip-associated subunit, CfaE. The current model of pilus-mediated adherence proposes that CFA/I has two distinct binding activities; the CfaE subunit is responsible for binding to receptors of unknown structure on erythrocyte and intestinal epithelial cell surfaces, while CfaB binds to various glycosphingolipids, including asialo-GM1. In this report, we present two independent lines of evidence that, contrary to the existing model, CfaB does not bind to asialo-GM1 independently of CfaE. Neither purified CfaB subunits nor CfaB assembled into pili bind to asialo-GM1. Instead, we demonstrate that binding activity toward asialo-GM1 resides in CfaE and this is essential for pilus binding to Caco-2 intestinal epithelial cells. We conclude that the binding activities of CFA/I pili for asialo-GM1, erythrocytes, and intestinal cells are inseparable, require the same amino acid residues in CfaE, and therefore depend on the same or very similar binding mechanisms. PMID:26975993

  16. [Molecular pathogenesis and therapeutic approach of GM2 gangliosidosis].

    PubMed

    Tsuji, Daisuke

    2013-01-01

    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 β-hexosaminidase α-subunits and β-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 (αβ heterodimer), resulting in progressive neurologic disorders. In Sandhoff disease, combined deficiencies of HexA and HexB (ββ 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

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

    SciTech Connect

    Petroulakis, E.; Cao, Z.; Salo, T.

    1994-09-01

    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.

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

    PubMed

    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

    GM2 gangliosidosis is a fatal lysosomal storage disease caused by a deficiency of β-hexosaminidase (EC 3.2.1.52). There are two major isoforms of the enzyme: hexosaminidase A composed of an α and a β subunit (encoded by HEXA and HEXB genes, respectively); and, hexosaminidase B composed of two β 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

  19. Segregative clustering of Lo and Ld membrane microdomains induced by local pH gradients in GM1-containing giant vesicles: a lipid model for cellular polarization.

    PubMed

    Staneva, Galya; Puff, Nicolas; Seigneuret, Michel; Conjeaud, Hélène; Angelova, Miglena I

    2012-11-27

    Several cell polarization processes are coupled to local pH gradients at the membrane surface. We have investigated the involvement of a lipid-mediated effect in such coupling. The influence of lateral pH gradients along the membrane surface on lipid microdomain dynamics in giant unilamellar vesicles containing phosphatidylcholine, sphingomyelin, cholesterol, and the ganglioside GM1 was studied. Lo/Ld phase separation was generated by photosensitization. A lateral pH gradient was established along the external membrane surface by acid local microinjection. The gradient promotes the segregation of microdomains: Lo domains within an Ld phase move toward the higher pH side, whereas Ld domains within an Lo phase move toward the lower pH side. This results in a polarization of the vesicle membrane into Lo and Ld phases poles in the axis of the proton source. A secondary effect is inward tubulation in the Ld phase. None of these processes occurs without GM1 or with the analog asialo-GM1. These are therefore related to the acidic character of the GM1 headgroup. LAURDAN fluorescence experiments on large unilamellar vesicles indicated that, with GM1, an increase in lipid packing occurs with decreasing pH, attributed to the lowering of repulsion between GM1 molecules. Packing increase is much higher for Ld phase vesicles than for Lo phase vesicles. It is proposed that the driving forces for domain vectorial segregative clustering and vesicle polarization are related to such differences in packing variations with pH decrease between the Lo and Ld phases. Such pH-driven domain clustering might play a role in cellular membrane polarization processes in which local lateral pH gradients are known to be important, such as migrating cells and epithelial cells. PMID:23121205

  20. Novel GM1 ganglioside-like peptide mimics prevent the association of cholera toxin to human intestinal epithelial cells in vitro.

    PubMed

    Yu, Robert K; Usuki, Seigo; Itokazu, Yutaka; Wu, Han-Chung

    2016-01-01

    Cholera is an acute diarrheal disease caused by infection in the gastrointestinal tract by the gram-negative bacterium, Vibrio cholerae, and is a serious public health threat worldwide. There has not been any effective treatment for this infectious disease. Cholera toxin (CT), which is secreted by V. cholerae, can enter host cells by binding to GM1, a monosialoganglioside widely distributed on the plasma membrane surface of various animal epithelial cells. The present study was undertaken to generate peptides that are conformationally similar to the carbohydrate epitope of GM1 for use in the treatment of cholera and related bacterial infection. For this purpose, we used cholera toxin B (CTB) subunit to select CTB-binding peptides that structurally mimic GM1 from a dodecamer phage-display library. Six GM1-replica peptides were selected by biopanning based on CTB recognition. Five of the six peptides showed inhibitory activity for GM1 binding to CTB. To test the potential of employing the peptide mimics for intervening with the bacterial infection, those peptides were examined for their binding capacity, functional inhibitory activity and in vitro effects using a human intestinal epithelial cell line, Caco-2 cells. One of the peptides, P3 (IPQVWRDWFKLP), was most effective in inhibiting cellular uptake of CTB and suppressing CT-stimulated cyclic adenosine monophosphate production in the cells. Our results thus provide convincing evidence that GM1-replica peptides could serve as novel agents to block CTB binding on epithelial cells and prevent the ensuing physiological effects of CT. PMID:26405107

  1. Chicken egg yolk anti-asialoGM1 immunoglobulin (IgY): an inexpensive glycohistochemical probe for localization of T-antigen in human colorectal adenocarcinomas.

    PubMed

    Sriram, V; Jebaraj, C E; Yogeeswaran, G

    1999-07-01

    A egg yolk polyclonal IgY has been prepared by immunization of white leghorn chickens with small unilamellar liposomal asialoGM1. The newly prepared anti-asialoGM1 IgY has been characterized to be specific toward the terminal carbohydrate moiety of asialoGM1, and has no cross reactivity to its sialylated counterpart (ganglioside, GM1) as evidenced by immunochromatographic studies. General glycohistochemical methods along with antigen specific lectin and immunohistochemical staining using anti-asialoGM1 IgY were used to study the expression of Thomsen-Friedenreich (T-) disaccharide antigen in human colorectal adenocarcinoma tissues. The expression of T-antigen in colon cancer tissue was detected by two T-disaccharide specific probes, chicken anti-T-yolk antibody (IgY) and Artocarpus integrifolia lectin (AIL) and was found to be more pronounced in both the secreted mucin as well as the cytoplasmic mucin deposits. These immunochemical detection methods for T-antigen showed a weaker correlation with other glycostaining methods using, alcian-blue/periodic acid-Schiff (AB-PAS) and high iron diamine (HID). However, a general enzymatic staining for galactose and galactosamine containing glycoconjugates, by galactose oxidase-Schiff method, showed a good correlation with T-antigen detection. While the T-beta specific anti-asialoGM1 could localize T-antigen in 11 of 13 (84%) human colorectal adenocarcinoma tissue sections tested, the T-alpha specific AIL could localize the T-antigen in only 6 of the tissues (46%). These observations confirm previously reported findings, of the prevalence of T-beta conformation in colon cancer, that binds significantly more with the anti-asialoGM1 IgY than with the T-alpha specific AIL. Hence, both anti-T IgY and the AIL immunohistochemical probes may have useful diagnostic value because of the ease of preparation and cost effectiveness, but the T-beta specific anti-asialoGM1 probe (IgY) would have a better prognostic value in colon

  2. Protease-resistant modified human β-hexosaminidase B ameliorates symptoms in GM2 gangliosidosis model.

    PubMed

    Kitakaze, Keisuke; Mizutani, Yasumichi; Sugiyama, Eiji; Tasaki, Chikako; Tsuji, Daisuke; Maita, Nobuo; Hirokawa, Takatsugu; Asanuma, Daisuke; Kamiya, Mako; Sato, Kohei; Setou, Mitsutoshi; Urano, Yasuteru; Togawa, Tadayasu; Otaka, Akira; Sakuraba, Hitoshi; Itoh, Kohji

    2016-05-01

    GM2 gangliosidoses, including Tay-Sachs and Sandhoff diseases, are neurodegenerative lysosomal storage diseases that are caused by deficiency of β-hexosaminidase A, which comprises an αβ heterodimer. There are no effective treatments for these diseases; however, various strategies aimed at restoring β-hexosaminidase A have been explored. Here, we produced a modified human hexosaminidase subunit β (HexB), which we have termed mod2B, composed of homodimeric β subunits that contain amino acid sequences from the α subunit that confer GM2 ganglioside-degrading activity and protease resistance. We also developed fluorescent probes that allow visualization of endocytosis of mod2B via mannose 6-phosphate receptors and delivery of mod2B to lysosomes in GM2 gangliosidosis models. In addition, we applied imaging mass spectrometry to monitor efficacy of this approach in Sandhoff disease model mice. Following i.c.v. administration, mod2B was widely distributed and reduced accumulation of GM2, asialo-GM2, and bis(monoacylglycero)phosphate in brain regions including the hypothalamus, hippocampus, and cerebellum. Moreover, mod2B administration markedly improved motor dysfunction and a prolonged lifespan in Sandhoff disease mice. Together, the results of our study indicate that mod2B has potential for intracerebrospinal fluid enzyme replacement therapy and should be further explored as a gene therapy for GM2 gangliosidoses. PMID:27018595

  3. Protease-resistant modified human β-hexosaminidase B ameliorates symptoms in GM2 gangliosidosis model

    PubMed Central

    Mizutani, Yasumichi; Sugiyama, Eiji; Tasaki, Chikako; Tsuji, Daisuke; Maita, Nobuo; Hirokawa, Takatsugu; Asanuma, Daisuke; Kamiya, Mako; Sato, Kohei; Setou, Mitsutoshi; Urano, Yasuteru; Togawa, Tadayasu; Otaka, Akira; Sakuraba, Hitoshi

    2016-01-01

    GM2 gangliosidoses, including Tay-Sachs and Sandhoff diseases, are neurodegenerative lysosomal storage diseases that are caused by deficiency of β-hexosaminidase A, which comprises an αβ heterodimer. There are no effective treatments for these diseases; however, various strategies aimed at restoring β-hexosaminidase A have been explored. Here, we produced a modified human hexosaminidase subunit β (HexB), which we have termed mod2B, composed of homodimeric β subunits that contain amino acid sequences from the α subunit that confer GM2 ganglioside–degrading activity and protease resistance. We also developed fluorescent probes that allow visualization of endocytosis of mod2B via mannose 6-phosphate receptors and delivery of mod2B to lysosomes in GM2 gangliosidosis models. In addition, we applied imaging mass spectrometry to monitor efficacy of this approach in Sandhoff disease model mice. Following i.c.v. administration, mod2B was widely distributed and reduced accumulation of GM2, asialo-GM2, and bis(monoacylglycero)phosphate in brain regions including the hypothalamus, hippocampus, and cerebellum. Moreover, mod2B administration markedly improved motor dysfunction and a prolonged lifespan in Sandhoff disease mice. Together, the results of our study indicate that mod2B has potential for intracerebrospinal fluid enzyme replacement therapy and should be further explored as a gene therapy for GM2 gangliosidoses. PMID:27018595

  4. Polycystic kidneys and GM2 gangliosidosis-like disease in neonatal springboks (Antidorcas marsupialis).

    PubMed

    Herder, V; Kummrow, M; Leeb, T; Sewell, A C; Hansmann, F; Lehmbecker, A; Wohlsein, P; Baumgärtner, W

    2015-05-01

    Clinical, gross, histopathologic, electron microscopic findings and enzymatic analysis of 4 captive, juvenile springboks (Antidorcas marsupialis) showing both polycystic kidneys and a storage disease are described. Springbok offspring (4 of 34; 12%) were affected by either one or both disorders in a German zoo within a period of 5 years (2008-2013). Macroscopic findings included bilaterally severely enlarged kidneys displaying numerous cysts in 4 animals and superior brachygnathism in 2 animals. Histopathologically, kidneys of 4 animals displayed cystic dilation of the renal tubules. In addition, abundant cytoplasmic vacuoles with a diameter ranging from 2 to 10 μm in neurons of the central and peripheral nervous system, hepatocytes, thyroid follicular epithelial cells, pancreatic islets of Langerhans and renal tubular cells were found in 2 springbok neonates indicative of an additional storage disease. Ultrastructurally, round electron-lucent vacuoles, up to 4 μm in diameter, were present in neurons. Enzymatic analysis of liver and kidney tissue of 1 affected springbok revealed a reduced activity of total hexosaminidase (Hex) with relatively increased HexA activity at the same level of total Hex, suggesting a hexosaminidase defect. Pedigree analysis suggested a monogenic autosomal recessive inheritance for both diseases. In summary, related springboks showed 2 different changes resembling both polycystic kidney and a GM2 gangliosidosis similar to the human Sandhoff disease. Whether the simultaneous occurrence of these 2 entities represents an incidental finding or has a genetic link needs to be investigated in future studies. PMID:25232033

  5. Reduced GM1 ganglioside in CFTR-deficient human airway cells results in decreased β1-integrin signaling and delayed wound repair

    PubMed Central

    Itokazu, Yutaka; Pagano, Richard E.; Schroeder, Andreas S.; O'Grady, Scott M.; Limper, Andrew H.

    2014-01-01

    Loss of cystic fibrosis transmembrane conductance regulator (CFTR) function reduces chloride secretion and increases sodium uptake, but it is not clear why CFTR mutation also results in progressive lung inflammation and infection. We previously demonstrated that CFTR-silenced airway cells migrate more slowly during wound repair than CFTR-expressing controls. In addition, CFTR-deficient cells and mouse models have been reported to have altered sphingolipid levels. Here, we investigated the hypothesis that reduced migration in CFTR-deficient airway epithelial cells results from altered sphingolipid composition. We used cell lines derived from a human airway epithelial cell line (Calu-3) stably transfected with CFTR short hairpin RNA (CFTR-silenced) or nontargeting short hairpin RNA (controls). Cell migration was measured by electric cell substrate impedance sensing (ECIS). Lipid analyses, addition of exogenous glycosphingolipids, and immunoblotting were performed. We found that levels of the glycosphingolipid, GM1 ganglioside, were ∼60% lower in CFTR-silenced cells than in controls. CFTR-silenced cells exhibited reduced levels of activated β1-integrin, phosphorylated tyrosine 576 of focal adhesion kinase (pFAK), and phosphorylation of Crk-associated substrate (pCAS). Addition of GM1 (but not GM3) ganglioside to CFTR-silenced cells restored activated β1-integrin, pFAK, and pCAS to near control levels and partially restored (∼40%) cell migration. Our results suggest that decreased GM1 in CFTR-silenced cells depresses β1-integrin signaling, which contributes to the delayed wound repair observed in these cells. These findings have implications for the pathology of cystic fibrosis, where altered sphingolipid levels in airway epithelial cells could result in a diminished capacity for wound repair after injury. PMID:24500283

  6. LIGA20, a lyso derivative of ganglioside GM1, given orally after cortical thrombosis reduces infarct size and associated cognition deficit.

    PubMed Central

    Kharlamov, A; Zivkovic, I; Polo, A; Armstrong, D M; Costa, E; Guidotti, A

    1994-01-01

    A bilateral photochemically induced thrombotic lesion of rat sensorimotor cortex (approximately 3 mm in diameter and 25 mm3 in volume) is associated with a persistent cognition (learning and memory) deficit, which was evaluated with water maze tasks. The N-dichloroacetylsphingosine derivative of lysoGM1 (LIGA20) administered after the lesion either i.v. or per or reduces the infarct size by 30-40% and attenuates the associated cognition deficits, presumably by limiting the extent of damage of neurons at risk located in the surroundings of the infarcted core (i.e., area penumbra). The LIGA20 protection is dose and time dependent. Maximal protection is afforded by a single dose of LIGA20 of 34 mumol/kg i.v. 1 hr after lesion or by a dose of 270 mumol/kg per os when administered 1 hr and 24 hr after the lesion. The protective effect of LIGA20 can be observed when the drug is administered i.v. up to 6 hr after the lesion. The protective efficacy of the oral administration of LIGA20 is related to its physiochemical properties, which, unlike those of GM1, allow absorption from the gastrointestinal tract. LIGA20 given orally reaches the brain promptly and rapidly inserts into the neuronal membranes. Here, by an unknown molecular mechanism, LIGA20 selectively reduces the pathological amplification of Ca2+ signaling elicited by persistent stimulation of ionotropic glutamate receptors in the area penumbra. PMID:8022776

  7. Meningoencephalitis-like onset of post-infectious AQP4-IgG-positive optic neuritis complicated by GM1-IgG-positive acute polyneuropathy.

    PubMed

    Benedetti, Luana; Franciotta, Diego; Beronio, Alessandro; Delucchi, Stefano; Capellini, Cesare; Del Sette, Massimo

    2015-02-01

    Fifteen days after a respiratory infection, a 45-year-old woman presented with paresthesias in the hands and feet, bilateral loss of vision, fever, headache, and impairment of consciousness. Magnetic resonance imaging (MRI) showed predominant lesions in the optic tracts, optic chiasm, and hypothalamus. Cerebrospinal fluid analysis revealed elevated protein level, and lymphocytic pleocytosis. Neurophysiological studies disclosed a demyelinating sensorimotor polyneuropathy. Serum anti-Mycoplasma pneumoniae immunoglobulin (Ig)M, anti-GM1 IgG, and anti-AQP4 IgG were positive. This case, which is remarkable for post-infectious meningoencephalitis-like onset, MRI picture, and dysimmunity to central and peripheral nervous system autoantigens, underpins the pivotal diagnostic role of anti-AQP4-IgG, and expands the list of clinico-pathological findings that can associate with neuromyelitis optica spectrum disorders. PMID:24557856

  8. Stem Cell Transplant for Inborn Errors of Metabolism

    ClinicalTrials.gov

    2012-11-06

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

  9. Characterization of the molecular defect in a feline model for type II GM2-gangliosidosis (Sandhoff disease).

    PubMed

    Muldoon, L L; Neuwelt, E A; Pagel, M A; Weiss, D L

    1994-05-01

    The Korat cat provides an animal model for type II GM2-gangliosidosis (Sandhoff disease) that may be suitable for tests of gene replacement therapy with the HEXB gene encoding the beta subunit of the beta-hexosaminidases. In the present report, we examined the brain and liver pathology of a typical Sandhoff-affected cat. We characterized the feline HEXB complementary DNA (cDNA) and determined the molecular defect in this feline model. cDNA libraries were produced from one normal and one affected animal, and cDNA clones homologous to human HEXB were sequenced. In the affected cDNA clone, the deletion of a cytosine residue at position +39 of the putative coding region results in a frame shift and a stop codon at base +191. This disease-related deletion was consistently detected by sequencing of cloned polymerase chain reaction amplified reverse transcribed messenger RNA from one more normal Korat and two additional affected animals. The defect was further demonstrated using single-strand conformational polymorphism analysis of the polymerase chain reaction products. In addition, alternative splicing of both normal and affected messenger RNAs was demonstrated. These results should facilitate the use of this animal model to assess gene therapy. PMID:8178934

  10. Measurement of the binding of cholera toxin to GM1 gangliosides on solid supported lipid bilayer vesicles and inhibition by europium (III) chloride.

    PubMed

    Williams, Thomas L; Jenkins, A Toby A

    2008-05-21

    In this paper the immobilization of small unilamellar DMPC/GM1 lipid vesicles containing a water-soluble bodipy dye is described. The binding of the complete alphabeta toxin expressed by Vibrio cholerae to the attached vesicles was measured using Surface Plasmon Resonance (SPR) and a value of the dissociation constant K d obtained. Further measurements showed that the interaction of both the alphabeta-toxin and the beta-subunit alone resulted in the permeation of the lipid membrane, with release of a fluorophore contained within the vesicle being measured by combined SPR and Surface Plasmon enhanced Fluorescence Spectroscopy (SPFS). The leakage of dye through the membrane, measured by following the change in fluorescence, was fitted to a simple diffusion model. Finally, SPFS measurements of the effect of europium(III) chloride (EuCl 3) showed that cholera toxin binding and subsequent membrane permeation could be blocked by 1 micromol dm (-3) europium chloride. In view of the low oral toxicity of europium chloride, we speculate on the potential pharmaceutical applications of this molecule in the treatment of cholera infection. PMID:18412339

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

    PubMed Central

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

    1986-01-01

    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

  12. Carbohydrate-to-carbohydrate interactions between α2,3-linked sialic acids on α2 integrin subunits and asialo-GM1 underlie the bone metastatic behaviour of LNCAP-derivative C4-2B prostate cancer cells

    PubMed Central

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

    2014-01-01

    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 α2,3-linked sialic acid, and α2β1 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 α2,3-linked sialic acid residues on α2 subunits of α2β1 integrin receptors, correlating with increased gene expression of α2,3-STs (sialyltransferases), particularly ST3GAL3. Cell surface α2,3-sialylation of α2 subunits was required for the integrin α2β1-dependent cell adhesion to collagen type I and the same α2,3-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 α2β1 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

  13. 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...

  14. Anti-glycoprotein D monoclonal antibody protects against herpes simplex virus type 1-induced diseases in mice functionally depleted of selected T-cell subsets or asialo GM1+ cells.

    PubMed Central

    Staats, H F; Oakes, J E; Lausch, R N

    1991-01-01

    Passive transfer of a monoclonal antibody (MAb) specific for glycoprotein D (gD) is highly effective in preventing the development of herpes simplex virus type 1-induced stromal keratitis. In the present study, we investigated whether animals which had been functionally depleted of T-cell subsets or asialo GM1+ cells would continue to be responsive to MAb therapy. BALB/c mice were depleted of CD4+, CD8+, or asialo GM1+ cells by treatment with anti-L3T4, anti-Lyt 2.2, or anti-asialo GM1 antibodies, respectively. Functional depletion of CD4+ cells was documented by the loss of delayed-type hypersensitivity responsiveness, while CD8+ cell depletion was accompanied by abrogation of cytotoxic lymphocyte activity. Anti-asialo GM1 treatment led to the loss of natural killer cell lytic activity. Mice depleted of the desired cell population and infected on the scarified cornea with herpes simplex virus type 1 uniformly developed necrotizing stromal keratitis by 3 weeks postinfection. A single inoculation of anti-gD MAb (55 micrograms) given intraperitoneally 24 h postinfection strongly protected hosts depleted of CD4+ cells against stromal keratitis. Likewise, antibody treatment in CD8+ or asialo GM1+ cell-depleted hosts was as therapeutically effective as that seen in non-cell-depleted mice. We also observed that in cell-depleted mice, the virus spread into the central nervous system and caused encephalitis. The CD4+ cell-depleted mice were the most severely affected, as 100% developed fatal disease. Anti-gD MAb treatment successfully protected all (32 of 32) CD4+-, CD8+-, or asialo GM1(+)-depleted hosts against encephalitis. We therefore conclude that antibody-mediated prevention of stromal keratitis and encephalitis does not require the obligatory participation of CD4+, CD8+, or asialo GM1+ cells. However, when mice were simultaneously depleted of both CD4+ and CD8+ T-cell subsets, antibody treatment could not prevent fatal encephalitis. Thus, antibody can compensate for

  15. X-ray reflectivity and grazing incidence diffraction studies of interaction between human adhesion/growth-regulatory galectin-1 and DPPE-GM1 lipid monolayer at an air/water interface.

    PubMed

    Majewski, J; André, S; Jones, E; Chi, E; Gabius, H-J

    2015-07-01

    The specific interaction of ganglioside GM1 with the homodimeric (prototype) endogenous lectin galectin-1 triggers growth regulation in tumor and activated effector T cells. This proven biorelevance directed interest to studying association of the lectin to a model surface, i.e. a 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine/ganglioside GM1 (80 : 20 mol%) monolayer, at a bioeffective concentration. Surface expansion by the lectin insertion was detected at a surface pressure of 20 mN/m. On combining the methods of grazing incidence X-ray diffraction and X-ray reflectivity, a transient decrease in lipid-ordered phase of the monolayer was observed. The measured electron density distribution indicated that galectin-1 is oriented with its long axis in the surface plane, ideal for cis-crosslinking. The data reveal a conspicuous difference to the way the pentameric lectin part of the cholera toxin, another GM1-specific lectin, is bound to the monolayer. They also encourage further efforts to monitor effects of structurally different members of the galectin family such as the functionally antagonistic chimera-type galectin-3. PMID:26542007

  16. Therapeutic Potential of Intracerebroventricular Replacement of Modified Human β-Hexosaminidase B for GM2 Gangliosidosis

    PubMed Central

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

    2011-01-01

    To develop a novel enzyme replacement therapy for neurodegenerative Tay-Sachs disease (TSD) and Sandhoff disease (SD), which are caused by deficiency of β-hexosaminidase (Hex) A, we designed a genetically engineered HEXB encoding the chimeric human β-subunit containing partial amino acid sequence of the α-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

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

    PubMed

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

    2011-06-01

    To develop a novel enzyme replacement therapy for neurodegenerative Tay-Sachs disease (TSD) and Sandhoff disease (SD), which are caused by deficiency of β-hexosaminidase (Hex) A, we designed a genetically engineered HEXB encoding the chimeric human β-subunit containing partial amino acid sequence of the α-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

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

    PubMed

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

    1995-04-01

    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

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

    PubMed Central

    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

    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

  20. Biomarkers of Central Nervous System Inflammation in Infantile and Juvenile Gangliosidoses

    PubMed Central

    Utz, Jeanine R.; Crutcher, Thomas; Schneider, Joseph; Sorgen, Patrick; Whitley, Chester B.

    2015-01-01

    Background The gangliosidoses (Tay-Sachs disease, Sandhoff disease and GM1-gangliosidosis) are progressive neurodegenerative diseases caused by lysosomal enzyme activity deficiencies and consequent accumulation of gangliosides in the central nervous system (CNS). The infantile forms are distinguished from the juvenile forms by age of onset, rate of disease progression and age of death. There are no approved treatments for the gangliosidoses. In search of potential biomarkers of disease, we quantified 188 analytes in CSF and serum from living human patients with longitudinal (serial) measurements. Notably, several associated with inflammation were elevated in the CSF of infantile gangliosidosis patients, and less so in more slowly progressing forms of juvenile gangliosidosis, but not in MPS disease. Thirteen CSF and two serum biomarker candidates were identified. Five candidate biomarkers were distinguished by persistent elevation in the CSF of patients with the severe infantile phenotype: ENA-78, MCP-1, MIP-1α, MIP-1β, TNFR2. Correspondence of abnormal elevation with other variables of disease --- i.e., severity of clinical phenotype, differentiation from changes in serum, and lack of abnormality in other neurodegenerative lysosomal diseases ---identifies these analytes as biomarkers of neuropathology specific to the gangliosidosis diseases. PMID:25557439

  1. Profiling oligosaccharidurias by electrospray tandem mass spectrometry: quantifying reducing oligosaccharides.

    PubMed

    Ramsay, Steven L; Meikle, Peter J; Hopwood, John J; Clements, Peter R

    2005-10-01

    A method to semiquantify urinary oligosaccharides from patients suffering from oligosaccharidurias is presented. 1-Phenyl-3-methyl-5-pyrazolone has been used to derivatize urinary oligosaccharides prior to analysis by electrospray ionization-tandem mass spectrometry (ESI-MS/MS). Disease-specific oligosaccharides were identified for several oligosaccharidurias, including GM1 gangliosidosis, GM2 gangliosidosis, sialic acid storage disease, sialidase/neuraminidase deficiency, galactosialidosis, I-cell disease, fucosidosis, Pompe and Gaucher diseases, and alpha-mannosidosis. The oligosaccharides were referenced against the internal standard, methyl lactose, to produce ratios for comparison with control samples. Elevations in specific urinary oligosaccharides were indicative of lysosomal disease and the defective catabolic enzyme. This method has been adapted to enable assay of large sample numbers and could readily be extended to other oligosaccharidurias and to monitor oligosaccharide levels in patients receiving treatment. It also has immediate potential for incorporation into a newborn screening program. PMID:16111643

  2. Systemic Gene Transfer of a Hexosaminidase Variant Using an scAAV9.47 Vector Corrects GM2 Gangliosidosis in Sandhoff Mice.

    PubMed

    Osmon, Karlaina J L; Woodley, Evan; Thompson, Patrick; Ong, Katalina; Karumuthil-Melethil, Subha; Keimel, John G; Mark, Brian L; Mahuran, Don; Gray, Steven J; Walia, Jagdeep S

    2016-07-01

    GM2 gangliosidosis is a group of neurodegenerative diseases caused by β-hexosaminidase A (HexA) enzyme deficiency. There is currently no cure. HexA is composed of two similar, nonidentical subunits, α and β, which must interact with the GM2 activator protein (GM2AP), a substrate-specific cofactor, to hydrolyze GM2 ganglioside. Mutations in either subunit or the activator can result in the accumulation of GM2 ganglioside within neurons throughout the central nervous system. The resulting neuronal cell death induces the primary symptoms of the disease: motor impairment, seizures, and sensory impairments. This study assesses the long-term effects of gene transfer in a Sandhoff (β-subunit knockout) mouse model. The study utilized a modified human β-hexosaminidase α-subunit (μ-subunit) that contains critical sequences from the β-subunit that enables formation of a stable homodimer (HexM) and interaction with GM2AP to hydrolyze GM2 ganglioside. We investigated a self-complementary adeno-associated viral (scAAV) vector expressing HexM, through intravenous injections of the neonatal mice. We monitored one cohort for 8 weeks and another cohort long-term for survival benefit, behavioral, biochemical, and molecular analyses. Untreated Sandhoff disease (SD) control mice reached a humane endpoint at approximately 15 weeks, whereas treated mice had a median survival age of 40 weeks, an approximate 2.5-fold survival advantage. On behavioral tests, the treated mice outperformed their knockout age-matched controls and perform similarly to the heterozygous controls. Through the enzymatic and GM2 ganglioside analyses, we observed a significant decrease in the GM2 ganglioside level, even though the enzyme levels were not significantly increased. Molecular analyses revealed a global distribution of the vector between brain and spinal cord regions. In conclusion, the neonatal delivery of a novel viral vector expressing the human HexM enzyme is effective in ameliorating the SD

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

    PubMed

    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

    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 β-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 β-hexosaminidase activity in cultured fibroblasts from Sandhoff patients. PMID:24356898

  4. Recurrent and novel GLB1 mutations in India.

    PubMed

    Bidchol, Abdul Mueed; Dalal, Ashwin; Trivedi, Rakesh; Shukla, Anju; Nampoothiri, Sheela; Sankar, V H; Danda, Sumita; Gupta, Neerja; Kabra, Madhulika; Hebbar, Shrikiran A; Bhat, Ramesh Y; Matta, Divya; Ekbote, Alka V; Puri, Ratna Dua; Phadke, Shubha R; Gowrishankar, Kalpana; Aggarwal, Shagun; Ranganath, Prajnya; Sharda, Sheetal; Kamate, Mahesh; Datar, Chaitanya A; Bhat, Kamalakshi; Kamath, Nutan; Shah, Hitesh; Krishna, Shuba; Gopinath, Puthiya Mundyat; Verma, Ishwar C; Nagarajaram, H A; Satyamoorthy, Kapaettu; Girisha, Katta Mohan

    2015-08-10

    GM1 gangliosidosis is a lysosomal storage disorder caused by mutations in the GLB1 gene, leading to the deficiency of the enzyme β-d-galactosidase. In this study, we report molecular findings in 50 Asian Indian families with GM1 gangliosidosis. We sequenced all the exons and flanking intronic sequences of GLB1 gene. We identified 33 different mutations (20 novel and 13 previously reported). The novel mutations include 12 missense (p.M1?, p.E129Q, p.G134R, p.L236P, p.G262E, p.L297F, p.Y331C, p.G414V, p.K493N, p.L514P, p.P597L, p.T600I), four splicing (c.246-2A>G, c.397-2A>G, c.552+1G>T, c.956-2A>G), three indels (p.R22Qfs*8, p.L24Cfs*47, p.I489Qfs*4) and one nonsense mutation (p.Q452*). Most common mutations identified in this study were c.75+2InsT (14%) and p.L337P (10%). Known mutations accounted for 67% of allele frequency in our cohort of patients, suggesting that these mutations in GLB1 are recurrent across different populations. Twenty three mutations were localized in the TIM barrel domain, β-domain 1 and β-domain 2. In silico sequence and structure analysis of GLB1 reveal that all the novel mutations affect the function and structure of the protein. We hereby report on the largest series of patients with GM1 gangliosidosis and the first from India. PMID:25936995

  5. I-cell disease. A case report and review of the literature.

    PubMed

    Güngör, N; Coşkun, T; Akçören, Z; Cağlar, M

    1994-01-01

    A four-month-old female infant having developmental delay, coarse facial features and dysostosis multiplex is reported with a special emphasis on the differential diagnosis among I-cell disease (ICD). Hurler syndrome and GM1 gangliosidosis. The lysosomal enzyme studies in cultured skin fibroblasts and serum sample of the patient certified the diagnosis of ICD. Foamy cell infiltration of some organs, including the lungs, and microgyria formation were also noted. Genetic counselling was provided and prenatal diagnosis was offered to the couple to detect ICD in the next pregnancy. PMID:8016916

  6. Sphingolipidoses in Turkey.

    PubMed

    Ozkara, Hatice Asuman; Topçu, Meral

    2004-09-01

    During the last 5 years 2057 children under the age of 5 with various neurologic symptoms with the suspected diagnosis of lysosomal storage diseases were referred to our hospital from different universities and state hospitals. We were able to separate sphingolipidoses by lysosomal enzyme screening. A total of 300 patients (15%) with sphingolipidoses were diagnosed; there were deficiencies of arylsulfatase A [metachromatic leukodystrophy (MLD)] in 93 (31%), hexosaminidase [Sandhoff disease (SHD)] in 62 (20.7%), hexosaminidase A [Tay-Sachs disease (TSD)] in 15 (5%), beta-galactosidase (GM1 gangliosidosis) in 35 (11.7%), alpha-galactosidase (Fabry disease) in one (0.3%) cerebroside beta-galactosidase (Krabbe disease) in 65 (21.7%) and glucosylceramidase (Gaucher disease) in 29 (9.6%). SHD (20.7%), MLD (31%) and Krabbe disease (21.7%) were common. Prenatal enzymatic diagnosis was made in 70 at risk pregnancies, 64 for TSD and SHD, three for MLD and three for GM1 gangliosidosis by using chorionic villus biopsy in 54, cord blood samples in 12 and cultured amniotic fluid cells in four. Seventeen fetuses were found to be affected. We have calculated the relative frequency and minimum incidence of sphingolipidoses in Turkey. The combined incidence of sphingolipidoses is 4.615 per 100,000 live births. The calculated incidences are 1.43, 0.95, 1, 0.23, 0.54, 0.45, 0.015 per 100,000 live births for MLD, SHD, Krabbe, Gaucher, TSD, GM1 gangliosidosis and Fabry diseases, respectively. The real incidence, which covers all subtypes of this group of diseases, should be greater than this number. The results suggested that, as a group, sphingolipidoses are relatively common and represent an important health problem in Turkey and some rare autosomal recessive diseases of Turkey are due to 'founder effect' created by consanguineous marriages. PMID:15275696

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

    PubMed

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

    2014-08-01

    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 β-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

  8. Population analysis of the GLB1 gene in South Brazil

    PubMed Central

    Baiotto, Cléia; Sperb, Fernanda; Matte, Ursula; da Silva, Cláudia Dornelles; Sano, Renata; Coelho, Janice Carneiro; Giugliani, Roberto

    2011-01-01

    Infantile GM1 gangliosidosis is caused by the absence or reduction of lysosomal beta-galactosidase activity. Studies conducted in Brazil have indicated that it is one of the most frequent lysosomal storage disorders in the southern part of the country. To assess the incidence of this disorder, 390 blood donors were tested for the presence of two common mutations (1622–1627insG and R59H) in the GLB1 gene. Another group, consisting of 26 GM1 patients, and the blood donors were tested for the presence of two polymorphisms (R521C and S532G), in an attempt to elucidate whether there is a founder effect. The frequencies of the R59H and 1622–1627insG mutations among the GM1 patients studied were 19.2% and 38.5%, respectively. The frequency of polymorphism S532G was 16.7%, whereas R521C was not found in the patients. The overall frequency of either R59H or 1622–1627insG was 57.7% of the disease-causing alleles. This epidemiological study suggested a carrier frequency of 1:58. Seven different haplotypes were found. The 1622–1627insG mutation was not found to be linked to any polymorphism, whereas linkage disequilibrium was found for haplotype 2 (R59H, S532G) (p < 0.001). These data confirm the high incidence of GM1 gangliosidosis and the high frequency of two common mutations in southern Brazil. PMID:21637542

  9. Measurement of isomeric yield ratios of 197m,gPt and 190m2,g+m1Ir from the 198Pt(γ,n) and natPt(γ,xn1p) reactions induced by 55-, 60-, and 65-MeV bremsstrahlung

    NASA Astrophysics Data System (ADS)

    Kye, Yong-Uk; Shin, Sung-Gyun; Cho, Moo-Hyun; Kim, Kyung Sook; Namkung, Won; Kim, Guinyun; Kim, Kwangsoo; Kang, Yeong-Rok; Lee, Man-Woo; Yang, Sung-Chul; Nguyen, Van Do; Pham, Duc Khue; Kim, Tien Thanh; Naik, Haladhara

    2015-05-01

    We have measured the isomeric yield ratios of 197m,gPt from the 198Pt(γ,n) reaction and 190m2,g+m1Ir from the natPt(γ,xn1p) reaction, induced with the bremsstrahlung end-point energies of 55-, 60-, and 65-MeV. The measurements were carried out by the activation method in combination with the direct γ-spectrometry. The experiments were performed at the 100 MeV electron linac of the Pohang Accelerator Laboratory (PAL). The obtained results at 55-, 60- and 65-MeV for the 197m,gPt from the 198Pt(γ,n) reaction are 0.166 ± 0.012, 0.174 ± 0.011, and 0.175 ± 0.011, whereas for the 190m2,g+m1Ir from the natPt(γ,xn1p) reaction are 0.072 ± 0.006, 0.084 ± 0.006 and 0.087 ± 0.006, respectively. The present results are measured for the first time over the investigated energy range. The present data are compared with the similar literature data at lower energy to examine the role of excitation energy.

  10. Diagnostic Approach to Childhood-onset Cerebellar Atrophy: A 10-Year Retrospective Study of 300 Patients

    PubMed Central

    Al-Maawali, Almundher; Blaser, Susan; Yoon, Grace

    2013-01-01

    Hereditary ataxias associated with cerebellar atrophy are a heterogeneous group of disorders. Selection of appropriate clinical and genetic tests for patients with cerebellar atrophy poses a diagnostic challenge. Neuroimaging is a crucial initial investigation in the diagnostic evaluation of ataxia in childhood, and the presence of cerebellar atrophy helps guide further investigations. We performed a detailed review of 300 patients with confirmed cerebellar atrophy on magnetic resonance imaging over a 10-year period. A diagnosis was established in 47% of patients: Mitochondrial disorders were most common, followed by the neuronal ceroid lipofuscinoses, ataxia telangectasia, and late GM2-gangliosidosis. We review the common causes of cerebellar atrophy in childhood and propose a diagnostic approach based on correlating specific neuroimaging patterns with clinical and genetic diagnoses. PMID:22764178

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

    PubMed

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

    1993-10-01

    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

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

    PubMed

    Tropak, Michael B; Mahuran, Don

    2007-10-01

    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

  13. Vacuolated lymphocytes signifying a metabolic disorder in an infant with developmental delay.

    PubMed

    Salama, Rasha; Zhou, Jiehao

    2016-01-01

    Metabolic disorders sometimes cause accumulation of metabolic byproducts which are manifested as cytoplasmic vacuoles in lymphocytes. We report the case of an infant with final diagnosis of GM1 gangliosidosis who initially presented with developmental delay and peripheral blood vacuolated lymphocytes. Blood film review is recommended in children suspicious for metabolic disorders. PMID:26783448

  14. Mitochondrial respiratory chain function in skeletal muscle of ALS patients.

    PubMed

    Echaniz-Laguna, Andoni; Zoll, Joffrey; Ribera, Florence; Tranchant, Christine; Warter, Jean-Marie; Lonsdorfer, Jean; Lampert, Eliane

    2002-11-01

    Evidence implicating mitochondrial dysfunction in the central nervous system of patients with sporadic amyotrophic lateral sclerosis (SALS) has recently been accumulating. In contrast, data on mitochondrial function in skeletal muscle in SALS are scarce and controversial. We investigated the in situ properties of muscle mitochondria in patients with early-stage SALS and sedentary (SED) controls using the skinned fiber technique to determine whether respiration of muscle tissue is altered in early-stage SALS in comparison with SED. Musculus vastus lateralis biopsies were obtained from 7 SED group members and 14 patients with early-stage SALS (mean disease duration, 9 months). Muscle fibers were permeabilized with saponine and then skinned and placed in an oxygraphic chamber to measure basal (V(0)) and maximal (V(max)) adenosine diphosphate-stimulated respiration rates and to assess mitochondrial regulation by adenosine diphosphate. Muscle oxidative capacity, evaluated with V(max), was identical in patients in the SALS and SED groups (V(0): SALS, 1.1 +/- 0.1; SED, 0.8 +/- 0.1, micromol 0(2). min(-1). gm(-1)dw and V(max): SALS, 3.1 +/- 0.3; SED, 2.5 +/- 0.3, micromol 0(2). min(-1). gm(-1)dw). This study shows an absence of large mitochondrial damage in skeletal muscle of patients with early-stage SALS, suggesting that mitochondrial dysfunction in the earlier stages of SALS is almost certainly not systemic. PMID:12402260

  15. Chaperone therapy for Krabbe disease: potential for late-onset GALC mutations.

    PubMed

    Hossain, Mohammad Arif; Higaki, Katsumi; Saito, Seiji; Ohno, Kazuki; Sakuraba, Hitoshi; Nanba, Eiji; Suzuki, Yoshiyuki; Ozono, Keiichi; Sakai, Norio

    2015-09-01

    Krabbe disease is an autosomal recessive leukodystrophy caused by a deficiency of the galactocerebrosidase (GALC) enzyme. Hematopoietic stem cells transplantation is the only available treatment option for pre-symptomatic patients. We have previously reported the chaperone effect of N-octyl-4-epi-β-valienamine (NOEV) on mutant GM1 β-galactosidase proteins, and in a murine GM1-gangliosidosis model. In this study, we examined its chaperone effect on mutant GALC proteins. We found that NOEV strongly inhibited GALC activity in cell lysates of GALC-transfected COS1 cells. In vitro NOEV treatment stabilized GALC activity under heat denaturation conditions. We also examined the effect of NOEV on cultured COS1 cells expressing mutant GALC activity and human skin fibroblasts from Krabbe disease patients: NOEV significantly increased the enzyme activity of mutants of late-onset forms. Moreover, we confirmed that NOEV could enhance the maturation of GALC precursor to its mature active form. Model structural analysis showed NOEV binds to the active site of human GALC protein. These results, for the first time, provide clear evidence that NOEV is a chaperone with promising potential for patients with Krabbe disease resulting from the late-onset mutations. PMID:26108143

  16. Multifocal motor neuropathy with conduction block: a study of 24 patients.

    PubMed Central

    Bouche, P; Moulonguet, A; Younes-Chennoufi, A B; Adams, D; Baumann, N; Meininger, V; Léger, J M; Said, G

    1995-01-01

    Twenty four patients with pure motor neuropathy are reported. The chronic motor involvement associated with fasciculations and cramps, mainly in the arms, led, in most patients, to an initial diagnosis of motor neuron disease. In some patients (nine of 24), there was no appreciable muscle atrophy. Tendon reflexes were often absent or weak. The finding of persistent multifocal conduction block confined to motor nerve fibres raises questions about the nature and the importance of this syndrome. Segmental reduction of motor conduction velocity occurred at the site of the block, but significant slowing of motor nerve conduction was not found outside this site. The response to intravenous IVIg treatment seems to be correlated with the absence of amyotrophy. Patients with little or no amyotrophy had an initial and sustained response to IVIg, and did not develop amyotrophy during the follow up study. They could be considered to have a variant of chronic inflammatory demyelinating polyneuropathy. Patients with pronounced amyotrophy independent of the disease duration did not respond as well to IVIg treatment, suggesting the existence of a distinct entity. Among the patients treated about two thirds who had an initial good response to IVIg had high or significant antiganglioside GM1 (anti-GM1) antibody titres, but there was no correlation between the high titres before treatment and long lasting response to IVIg treatment. Images PMID:7608707

  17. Sustained normalization of neurological disease after intracranial gene therapy in a feline model**

    PubMed Central

    McCurdy, Victoria J.; Johnson, Aime K.; Gray-Edwards, Heather; Randle, Ashley N.; Brunson, Brandon L.; Morrison, Nancy E.; Salibi, Nouha; Johnson, Jacob A.; Hwang, Misako; Beyers, Ronald J.; Leroy, Stanley G.; Maitland, Stacy; Denney, Thomas S.; Cox, Nancy R.; Baker, Henry J.; Sena-Esteves, Miguel; Martin, Douglas R.

    2015-01-01

    Progressive debilitating neurological defects characterize feline GM1 gangliosidosis, a lysosomal storage disease caused by deficiency of lysosomal β-galactosidase. No effective therapy exists for affected children, who often die before age 5. In the current study, an adeno-associated viral vector carrying the therapeutic gene was injected bilaterally into two brain targets (thalamus and deep cerebellar nuclei) of a feline model of GM1 gangliosidosis. Gene therapy normalized β-galactosidase activity and storage throughout the brain and spinal cord. The mean survival of 12 treated GM1 animals was >38 months compared to 8 months for untreated animals. Seven of the 8 treated animals remaining alive demonstrated normalization of disease, with abrogation of many symptoms including gait deficits and postural imbalance. Sustained correction of the GM1 gangliosidosis disease phenotype after limited intracranial targeting by gene therapy in a large animal model suggests that this approach may be useful for treating the human version of this lysosomal storage disorder. PMID:24718858

  18. Three Novel Mutations in Iranian Patients with Tay-Sachs Disease

    PubMed Central

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

    2014-01-01

    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

  19. Magnetic resonance findings of the corpus callosum in canine and feline lysosomal storage diseases.

    PubMed

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

    2013-01-01

    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

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

    PubMed Central

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

    2013-01-01

    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

  1. Synthesis of lipophilic 1-deoxygalactonojirimycin derivatives as D-galactosidase inhibitors.

    PubMed

    Schitter, Georg; Scheucher, Elisabeth; Steiner, Andreas J; Stütz, Arnold E; Thonhofer, Martin; Tarling, Chris A; Withers, Stephen G; Wicki, Jacqueline; Fantur, Katrin; Paschke, Eduard; Mahuran, Don J; Rigat, Brigitte A; Tropak, Michael; Wrodnigg, Tanja M

    2010-01-01

    N-Alkylation at the ring nitrogen of the D-galactosidase inhibitor 1-deoxygalactonojirimycin with a functionalised C ₆alkyl chain followed by modification with different aromatic substituents provided lipophilic 1-deoxygalactonojirimycin derivatives which exhibit inhibitory properties against β-glycosidases from E. coli and Agrobacterium sp. as well as green coffee bean α-galactosidase. In preliminary studies, these compounds also showed potential as chemical chaperones for GM1-gangliosidosis related β-galactosidase mutants. PMID:20502610

  2. A capillary electrophoresis procedure for the screening of oligosaccharidoses and related diseases.

    PubMed

    Casado, Mercedes; Altimira, Laura; Montero, Raquel; Castejón, Esperanza; Nascimento, Andrés; Pérez-Dueñas, Belén; Ormazabal, Aida; Artuch, Rafael

    2014-07-01

    The most widely used method for the biochemical screening of oligosaccharidoses is the analysis of the urinary oligosaccharide pattern by thin-layer chromatography on silica gel plates. However, this method is not always sensitive enough, and it is extremely time-consuming and laborious. In this work, the analysis of the urine oligosaccharide pattern was standardized for the first time by using capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection (Beckman P/ACE MDQ) with a 488-nm argon ion laser module. All of the analyses were conducted using the Carbohydrate Labeling and Analysis Kit (Beckman-Coulter), which derivatizes samples with 8-aminopyrene-1,3,6-trisulfonate. Urine samples from 40 control subjects (age range, 1 week to 16 years) and from ten patients diagnosed with eight different lysosomal diseases (six of them included in the Educational Oligosaccharide Kit from ERNDIM EQA schemes) were analyzed. Two oligosaccharide excretion patterns were established in our control population according to age (younger or older than 1 year of age). Abnormal peaks with slower migration times than the tetrasaccharide position were observed for fucosidosis, α-mannosidosis, GM1 gangliosidosis, GM2 gangliosidosis variant 0, Pompe disease, and glycogen storage disease type 3. In conclusion, the first CE-LIF method to screen for oligosaccharidoses and related diseases, which also present oligosacchariduria, has been standardized. In all of the cases, the urine oligosaccharide analysis was strongly informative and showed abnormal patterns that were not present in any of the urine samples from the control subjects. Only urine from patients with aspartylglucosaminuria and Schindler disease displayed normal results. PMID:24788891

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

    PubMed Central

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

    1990-01-01

    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

  4. The role of pharmacotherapy in modifying the neurological status of patients with spinal and spinal cord injuries.

    PubMed

    do Vale Ramos, Renato Carlos; Alegrete, Nuno

    2015-01-01

    The aim here was to conduct a review of the literature on pharmacological therapies for modifying the neurological status of patients with spinal cord injuries. The PubMed database was searched for articles with the terms "spinal cord injury AND methylprednisolone/GM1/apoptosis inhibitor/calpain inhibitor/naloxone/tempol/tirilazad", in Portuguese or in English, published over the last five years. Older studies were included because of their historical importance. The pharmacological groups were divided according to their capacity to interfere with the physiopathological mechanisms of secondary injuries. Use of methylprednisolone needs to be carefully weighed up: other anti-inflammatory agents have shown benefits in humans or in animals. GM1 does not seem to have greater efficacy than methylprednisolone, but longer-term studies are needed. Many inhibitors of apoptosis have shown benefits in in vitro studies or in animals. Naloxone has not shown benefits. Tempol inhibits the main consequences of oxidation at the level of the spinal cord and other antioxidant drugs seem to have an effect superior to that of methylprednisolone. There is an urgent need to find new treatments that improve the neurological status of patients with spinal cord injuries. The benefits from treatment with methylprednisolone have been questioned, with concerns regarding its safety. Other drugs have been studied, and some of these may provide promising alternatives. Additional studies are needed in order to reach conclusions regarding the benefits of these agents in clinical practice. PMID:27218071

  5. The role of pharmacotherapy in modifying the neurological status of patients with spinal and spinal cord injuries☆

    PubMed Central

    do Vale Ramos, Renato Carlos; Alegrete, Nuno

    2015-01-01

    The aim here was to conduct a review of the literature on pharmacological therapies for modifying the neurological status of patients with spinal cord injuries. The PubMed database was searched for articles with the terms “spinal cord injury AND methylprednisolone/GM1/apoptosis inhibitor/calpain inhibitor/naloxone/tempol/tirilazad”, in Portuguese or in English, published over the last five years. Older studies were included because of their historical importance. The pharmacological groups were divided according to their capacity to interfere with the physiopathological mechanisms of secondary injuries. Use of methylprednisolone needs to be carefully weighed up: other anti-inflammatory agents have shown benefits in humans or in animals. GM1 does not seem to have greater efficacy than methylprednisolone, but longer-term studies are needed. Many inhibitors of apoptosis have shown benefits in in vitro studies or in animals. Naloxone has not shown benefits. Tempol inhibits the main consequences of oxidation at the level of the spinal cord and other antioxidant drugs seem to have an effect superior to that of methylprednisolone. There is an urgent need to find new treatments that improve the neurological status of patients with spinal cord injuries. The benefits from treatment with methylprednisolone have been questioned, with concerns regarding its safety. Other drugs have been studied, and some of these may provide promising alternatives. Additional studies are needed in order to reach conclusions regarding the benefits of these agents in clinical practice. PMID:27218071

  6. Lectin histochemistry and ultrastructure of feline kidneys from six different storage diseases.

    PubMed

    Castagnaro, M; Alroy, J; Ucci, A A; Glew, R H

    1987-01-01

    We have compared the pattern of lectin staining with the ultrastructural features of kidneys from normal cats and 19 cats with 6 different lysosomal storage diseases. The diseases studied include GM1 and GM2 gangliosidosis, mucopolysaccharidosis (MPS)-I and MPS-VI, sphingomyelin-lipidosis (i.e., Niemann-Pick disease) and mannosidosis. Ten different biotinylated lectins were used as histochemical probes for carbohydrate residues and avidin-biotin-peroxidase complex as visualant. Concanavalia ensiformis agglutinin (Con A) stained mesangial cells in all storage diseases but GM1, epithelial cells in sphingomyelin-lipidosis and mannosidosis, endothelial cells in GM1 and mannosidosis and Bowman's capsule cells in all but GM2. Griffonia simplicifolia agglutinin I (GS-I) stained the glomerular endothelium in all six diseases, but not in control kidneys. Ricinus communis agglutinin-I (RCA-I) stained the glomerular epithelium only in GM1 and MPS-I. Succinylated wheat germ agglutinin (SWGA) stained the glomerular endothelium and epithelium in mannosidosis, and the glomerular epithelium and Bowman's capsule in MPS-I. Ultrastructure studies demonstrated an accumulation of oligosaccharides in cases of mannosidosis and GM1 gangliosidosis, a mixture of oligosaccharides and lipids in MPS-I, MPS-VI and GM2 gangliosidosis and only lipid storage in sphingomyelin lipidosis. These studies show that morphologic and histochemical changes are manifested in some kidney cell types in lysosomal storage diseases, even though the enzyme deficiency occurs in all cell types. Furthermore, we show that the nature of the undegraded stored material is complex and that other factors, such as rate of membrane turn over, membrane composition, and cell function may influence the amount and nature of the "stored" material. PMID:2892300

  7. Genetics Home Reference: GM2-gangliosidosis, AB variant

    MedlinePlus

    ... Accessibility FOIA Viewers & Players U.S. Department of Health & Human Services National Institutes of Health National Library of Medicine Lister Hill National Center for Biomedical Communications 8600 Rockville Pike, Bethesda, MD 20894, USA HONCode ...

  8. 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

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

    1989-04-01

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

  9. Gangliosidoses.

    PubMed

    Patterson, Marc C

    2013-01-01

    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 β-galactosidase and β-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

  10. Congenital ocular motor apraxia associated with idiopathic generalized epilepsy in monozygotic twins.

    PubMed

    Gonzalez-Martin, J A; Kaye, L C; Brown, M; Ellis, I; Appelton, R; Kaye, S B

    2004-06-01

    Identical female twins (age 11 years) with congenital ocular motor apraxia and generalized idiopathic epilepsy are reported. Their presenting symptoms were a long history of abnormal head and eye movements. One twin developed partial sensory seizures. The patients underwent 16-channel EEG, electro-oculographic recordings, MRI of the brain, and genetic and metabolic investigations. EEG findings were consistent with idiopathic generalized epilepsy. Electrooculographic recordings of the saccades confirmed an inability to elicit horizontal saccades without preceding head movement; saccades to the left were better than saccades to the right. MR scans for one twin showed normal findings, however, for the twin who had meningitis they revealed asymmetry between the right and left temporal lobes but no specific abnormality. DNA analysis using a series of autosomal polymorphic markers confirmed the monozygocity of the twins. White blood cell enzyme analysis excluded Sandhoff disease, Tay-Sachs disease, GM1 gangliosidosis, metacromatic leucodystrophy, Gaucher disease, Niemann-Pick disease (A and B), and Krabbe leucodystrophy. Albumin and immunoglobulin (IgA, IgG, and IgM) levels were normal. It is concluded that autosomal recessive inheritance seems the most likely explanation here, as recent studies have found insertion and missense mutations of the aprataxin gene which have been related to an early onset form of ataxia with ocular motor apraxia and hypoalbuminaemia. PMID:15174536

  11. Glycosidases: inborn errors of glycosphingolipid catabolism.

    PubMed

    Ashida, Hisashi; Li, Yu-Teh

    2014-01-01

    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

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

    PubMed

    Uribe, Alfredo; Giugliani, Roberto

    2013-01-01

    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 α-galactosidase A, α glucosidase, α-L-iduronidase, arylsulfatase B, β-galactosidase, β-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

  13. A pilot study of gene testing of genetic bone dysplasia using targeted next-generation sequencing.

    PubMed

    Zhang, Huiwen; Yang, Rui; Wang, Yu; Ye, Jun; Han, Lianshu; Qiu, Wenjuan; Gu, Xuefan

    2015-12-01

    Molecular diagnosis of genetic bone dysplasia is challenging for non-expert. A targeted next-generation sequencing technology was applied to identify the underlying molecular mechanism of bone dysplasia and evaluate the contribution of these genes to patients with bone dysplasia encountered in pediatric endocrinology. A group of unrelated patients (n=82), characterized by short stature, dysmorphology and X-ray abnormalities, of which mucopolysacharidoses, GM1 gangliosidosis, mucolipidosis type II/III and achondroplasia owing to FGFR3 G380R mutation had been excluded, were recruited in this study. Probes were designed to 61 genes selected according to the nosology and classification of genetic skeletal disorders of 2010 by Illumina's online DesignStudio software. DNA was hybridized with probes and then a library was established following the standard Illumina protocols. Amplicon library was sequenced on a MiSeq sequencing system and the data were analyzed by MiSeq Reporter. Mutations of 13 different genes were found in 44 of the 82 patients (54%). Mutations of COL2A1 gene and PHEX gene were found in nine patients, respectively (9/44=20%), followed by COMP gene in 8 (18%), TRPV4 gene in 4 (9%), FBN1 gene in 4 (9%), COL1A1 gene in 3 (6%) and COL11A1, TRAPPC2, MATN3, ARSE, TRPS1, SMARCAL1, ENPP1 gene mutations in one patient each (2% each). In conclusion, mutations of COL2A1, PHEX and COMP gene are common for short stature due to bone dysplasia in outpatient clinics in pediatric endocrinology. Targeted next-generation sequencing is an efficient way to identify the underlying molecular mechanism of genetic bone dysplasia. PMID:26377240

  14. A study of the strategic alliance for EMS industry: the application of a hybrid DEA and GM (1, 1) approach.

    PubMed

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

    2015-01-01

    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

  15. Bis(monoacylglycero)phosphate: a secondary storage lipid in the gangliosidoses

    PubMed Central

    Akgoc, Zeynep; Sena-Esteves, Miguel; Martin, Douglas R.; Han, Xianlin; d’Azzo, Alessandra; Seyfried, Thomas N.

    2015-01-01

    Bis(monoacylglycero)phosphate (BMP) is a negatively charged glycerophospholipid with an unusual sn-1;sn-1′ structural configuration. BMP is primarily enriched in endosomal/lysosomal membranes. BMP is thought to play a role in glycosphingolipid degradation and cholesterol transport. Elevated BMP levels have been found in many lysosomal storage diseases (LSDs), suggesting an association with lysosomal storage material. The gangliosidoses are a group of neurodegenerative LSDs involving the accumulation of either GM1 or GM2 gangliosides resulting from inherited deficiencies in β-galactosidase or β-hexosaminidase, respectively. Little information is available on BMP levels in gangliosidosis brain tissue. Our results showed that the content of BMP in brain was significantly greater in humans and in animals (mice, cats, American black bears) with either GM1 or GM2 ganglioside storage diseases, than in brains of normal subjects. The storage of BMP and ganglioside GM2 in brain were reduced similarly following adeno-associated viral-mediated gene therapy in Sandhoff disease mice. We also found that C22:6, C18:0, and C18:1 were the predominant BMP fatty acid species in gangliosidosis brains. The results show that BMP accumulates as a secondary storage material in the brain of a broad range of mammals with gangliosidoses. PMID:25795792

  16. Bis(monoacylglycero)phosphate: a secondary storage lipid in the gangliosidoses.

    PubMed

    Akgoc, Zeynep; Sena-Esteves, Miguel; Martin, Douglas R; Han, Xianlin; d'Azzo, Alessandra; Seyfried, Thomas N

    2015-05-01

    Bis(monoacylglycero)phosphate (BMP) is a negatively charged glycerophospholipid with an unusual sn-1;sn-1' structural configuration. BMP is primarily enriched in endosomal/lysosomal membranes. BMP is thought to play a role in glycosphingolipid degradation and cholesterol transport. Elevated BMP levels have been found in many lysosomal storage diseases (LSDs), suggesting an association with lysosomal storage material. The gangliosidoses are a group of neurodegenerative LSDs involving the accumulation of either GM1 or GM2 gangliosides resulting from inherited deficiencies in β-galactosidase or β-hexosaminidase, respectively. Little information is available on BMP levels in gangliosidosis brain tissue. Our results showed that the content of BMP in brain was significantly greater in humans and in animals (mice, cats, American black bears) with either GM1 or GM2 ganglioside storage diseases, than in brains of normal subjects. The storage of BMP and ganglioside GM2 in brain were reduced similarly following adeno-associated viral-mediated gene therapy in Sandhoff disease mice. We also found that C22:6, C18:0, and C18:1 were the predominant BMP fatty acid species in gangliosidosis brains. The results show that BMP accumulates as a secondary storage material in the brain of a broad range of mammals with gangliosidoses. PMID:25795792

  17. Glucosylceramide modulates endolysosomal pH in Gaucher disease.

    PubMed

    Sillence, Dan J

    2013-06-01

    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

  18. Patient satisfaction.

    PubMed

    Prakash, Bhanu

    2010-09-01

    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

  19. Neuropsychiatric aspects of the adult variant of Tay-Sachs disease.

    PubMed

    MacQueen, G M; Rosebush, P I; Mazurek, M F

    1998-01-01

    Tay-Sachs disease (a GM2 gangliosidosis) is an inherited neuronal storage disease that can affect individuals across the age spectrum. Psychosis is reported in 30% to 50% of adult-onset patients, and many are misdiagnosed with schizophrenia. Mood disorders are present in more than 25% and cognitive impairment in more than 20%. Treatment of psychosis with neuroleptics may not have a favorable risk/benefit ratio, but treatment with benzodiazepines or electroconvulsive therapy may be efficacious. Metabolic diseases such as gangliosidosis are probably under-recognized as causes of neuropsychiatric illness. Increased awareness of these disorders will lead to accurate diagnosis, appropriate treatment selection, and genetic counseling. PMID:9547461

  20. Modified beta-D-N-acetylhexosaminidase isozymes for enzyme replacement in GM2 gangliosidosis.

    PubMed

    Rattazzi, M C; Dobrenis, K; Joseph, A; Schwartz, P

    1987-01-01

    The therapeutic potential of enzyme replacement in lysosomal storage disorders has remained largely unfulfilled, perhaps because of negative reactions to the initial disappointing results. Despite the existence of several animal models that can be utilized to explore solutions to the problems of exogenous enzyme targeting, the interest in ERT prevalent during the 1970's seems to have subsided to be replaced by active interest in bone marrow transplantation (BMT, Krivit and Paul [1986]). This is a logical approach to enzyme replacement in storage disorders of the RE system, and indeed some encouraging results have been obtained. However, in addition to having high morbidity and mortality, in the ultimate analysis BMT presents the same targeting problems as conventional ERT. In our opinion, these problems can be solved more easily in the case of ERT by exploiting the existing cellular uptake mechanisms and infusing enzymes whose structure has been suitably modified by simple biochemical manipulations. Accordingly, we have explored a methodology that takes advantage of negative charges on the cell surface to obtain nonspecific but effective membrane binding of beta-hex coupled to the highly positively charged PLL, followed by internalization and routing to the lysosomes. This system increases uptake of exogenous enzyme by some neurons in vitro and possibly in vivo, but its efficiency depends on the cells' endocytic activity that, in the case of neuronal soma, apparently is low. Thus, we have chosen as recognition marker for specific neuronal uptake a nontoxic fragment of TTx that is efficiently taken up by these cells. The initial results are encouraging; they support our contention that effective enzyme replacement methodologies can be devised, and encourage us to continue our work in this direction. Finally, recombinant DNA techniques are now being applied to a number of LSD, and the genes for several of the pertinent enzymes have been or are being isolated. In addition to representing a first step towards gene replacement therapy, the results of this work will permit the generation of large amounts of human enzymes from bacteria by recombinant DNA methods, thus obviating the problem of enzyme supply for ERT. Since human lysosomal enzymes obtained from bacteria will be nonglycosylated, to obtain cell uptake it will be necessary to resort to the type of modifications that we are trying to develop at this time, i.e., covalent linkage to moieties that allow non-glycosyl-mediated cellular uptake. Thus, our work on beta-hex may provide a model for biochemical manipulations of bacterially produced enzymes applicable to several LSD. PMID:2956216

  1. Mechanism of abnormal growth in astrocytes derived from a mouse model of GM2 gangliosidosis.

    PubMed

    Kawashima, Nagako; Tsuji, Daisuke; Okuda, Tetsuya; Itoh, Kohji; Nakayama, Ken-ichi

    2009-11-01

    Sandhoff disease is a progressive neurodegenerative disorder caused by mutations in the HEXB gene which encodes the beta-subunit of N-acetyl-beta-hexosaminidase A and B, resulting in the accumulation of the ganglioside GM2. We isolated astrocytes from the neonatal brain of Sandhoff disease model mice in which the N-acetyl-beta-hexosaminidase beta-subunit gene is genetically disrupted (ASD). Glycolipid profiles revealed that GM2/GA2 accumulated in the lysosomes and not on the cell surface of ASD astrocytes. In addition, GM3 was increased on the cell surface. We found remarkable differences in the cell proliferation of ASD astrocytes when compared with cells isolated from wild-type mice, with a faster growth rate of ASD cells. In addition, we observed increased extracellular, signal-regulated kinase (ERK) phosphorylation in ASD cells, but Akt phosphorylation was decreased. Furthermore, the phosphorylation of ERK in ASD cells was not dependent upon extracellular growth factors. Treatment of ASD astrocytes with recombinant N-acetyl-beta-hexosaminidase A resulted in a decrease of their growth rate and ERK phosphorylation. These results indicated that the up-regulation of ERK phosphorylation and the increase in proliferation of ASD astrocytes were dependent upon GM2/GA2 accumulation. These findings may represent a mechanism in linking the nerve cell death and reactive gliosis observed in Sandhoff disease. PMID:19765188

  2. Beta-hexosaminidase isozymes and replacement therapy in Gm2 gangliosidosis.

    PubMed

    Rattazzi, M C

    1983-01-01

    The problem of cell targeting of lysosomal enzymes is a critical one in the development of strategies for therapeutic enzyme replacement in lysosomal storage diseases. In principle, posttranscriptional isozymes with different carbohydrate-chain composition may be helpful in exploiting existing glycosyl-specific receptors on target cells, if the receptor specificities are known and match the glycosyl composition of available isozymes. In practice, however, the choice is limited to isozymes that can be obtained from tissues available in abundance, such as placenta or blood plasma. Our early experiments show that one can interfere with the interaction between hepatic (RES) receptor and enzyme glycosyl chain, to obtain extrahepatic targeting of beta-hexosaminidase, with catabolic effects. This approach, of course, does not have an immediate therapeutic application, as it involves injection of large amounts of foreign material in order to inhibit hepatic uptake. Modification of the glycosyl chain may be the method of choice in selected instances [Furbish et al. 1981], but is applicability again depends on the knowledge of receptor specificity on target cells and on composition of the glycosyl chain of the enzyme in question. Our recent experiments are a first step toward obtaining enzyme forms that can be endocytosed efficiently by mechanisms that are independent of glycosyl-specific receptors. Charge-mediated, absorptive endocytosis can be obtained by covalent coupling of cationic PLL to beta-hexosaminidase. Given the abundance of negative surface charges on most cell types [Weiss, 1969], this approach may be applicable to different target cells and organs, and possibly also to lysosomal enzymes other than beta-hexosaminidase. The existence of glycosyl recognition signals on beta-hexosaminidase can be obviated by simple chemical manipulations, such as Na-metaperiodate oxidation, which effectively prevents hepatic RES uptake [Rattazzi et al, 1982]. In combination with PLL conjugation, this may ultimately result in an enzyme form that escapes the undesired, preferential RES uptake and is efficiently endocytosed by most cells. It will remain to be seen if this artificially created isozyme (for which we propose the name "ersatzyme") is catabolically effective. This can easily be verified in our animal model, along the lines followed to demonstrate the catabolic effects of native Hex A. Finally, the recent developments in molecular genetics, which allows production of human proteins in bacterial systems by recombinant DNA techniques, make it very likely that abundant beta-hexosaminidase may be similarly obtained for therapeutic applications.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:6227586

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

    PubMed

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

    2012-08-01

    The GM2 gangliosidoses are fatal lysosomal storage diseases principally affecting the brain. Absence of β-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 β-hexosaminidase α (HEXA) and β (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 β-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

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

    PubMed

    Chmiel, James F; Davis, Pamela B

    2003-01-01

    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

  5. Carrier rates of four single-gene disorders in Croatian Bayash Roma.

    PubMed

    Barešić, Ana; Peričić Salihović, Marijana

    2014-02-01

    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 Međimurje 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

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

    PubMed Central

    Barešić, Ana

    2014-01-01

    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 Međimurje 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

  7. Discharging patients.

    PubMed

    Causey, Amy

    2016-06-22

    What was the nature of the CPD activity and/or practice-related feedback and/or event or experience in your practice? The CPD article discussed the importance of effective planning when discharging patients from acute care hospitals. It emphasised the benefit of early assessment and planning, and outlined the essential principles that should be followed when discharging a patient. PMID:27332612

  8. Patient Roadmap

    MedlinePlus

    ... Follow ATA’s Patient Roadmap for the step-by-step process of how to achieve the best results. Find ... Patient Roadmap,” that identifies the optimal step-by-step process for finding medical support. Please note: this “Roadmap” ...

  9. Patient education.

    PubMed

    Lindeman, C A

    1988-01-01

    The 120 studies included in this review were grouped in relation to five categories of variables basic to a theory of instruction in patient education. Findings in the studies related to the characteristics of the patient as learner support the following variables as significant for a theory of instruction: demographic characteristics including age, race, duration and type of illness, educational level, and family preparedness. Selected psychological variables are significant as they interact with teaching approaches. Given only two studies in which the characteristics of the nurse as teacher were the main variables, no inferences for a theory of instruction could be drawn. However, the findings from those studies combined with results from studies in which characteristics of the nurse were secondary variables support the importance of this category of variables. The educational preparation, motivation, values, and job description of the nurse implementing patient teaching appear to be significant variables for a theory of instruction. Investigators explored a wide range of teaching strategies in the studies of patient teaching. The setting for teaching, group and individual teaching, and a variety of instructional strategies all prove promising at the operational level. The instructional strategies were too diverse to allow analysis at a level of abstraction beyond the operational. Findings in this review also support characteristics of the health care setting as an important category of variables for a theory of instruction. The organizational structure, a quality assurance framework, and valuing patient teaching appear to be significant variables. Patient education research provides a rich data source for future developments in theory, practice, and research. The effectiveness of patient education as a nursing intervention is clearly established. Furthermore, positive learning outcomes are associated with a broad range of teaching strategies, content areas, and

  10. Patient Empowerment

    MedlinePlus

    ... cancer patient organization. Ask for this help. Your Responsibilities Keep Good Records Get in the habit of ... responsible for your follow-up. You should take responsibility for getting a follow-up scheduled and for ...

  11. Extensive Mongolian spots: a clinical sign merits special attention.

    PubMed

    Ashrafi, Mahmood Reza; Shabanian, Reza; Mohammadi, Mahmood; Kavusi, Susan

    2006-02-01

    Although typical and limited Mongolian spots are benign skin markings at birth which fade and disappear as the child grows, extensive Mongolian spots deserve special attention as possible indications of associated inborn error of metabolism. A few cases of extensive Mongolian spots in association with inheritable storage diseases have been reported. Some hypotheses have been put forward, but further investigation is necessary to elucidate the causative factors. This report describes three infants with generalized Mongolian spots, two infants with GM1 gangliosidosis type 1, and one in association with Hurler syndrome. Findings of generalized Mongolian spots in newborns may lead to an early detection and early treatment before irreversible organ damage occurs. PMID:16458829

  12. 4-Trifluoromethylumbelliferyl glycosides as new substrates for revealing diseases connected with hereditary deficiency of lysosome glycosidases.

    PubMed

    Karpova, E A; Voznyi YaV; Dudukina, T V; Tsvetkova, I V

    1991-08-01

    The following glycosides of 4-trifluoromethylumbelliferone: alpha-D-mannopyranoside, alpha-L-fucopyranoside, alpha-D-glucopyranoside, beta-D-glucopyranoside, alpha-D-galactopyranoside, beta-D-galactopyranoside, alpha-L-iduronide and beta-D-glucuronide were studied. 4-Trifluoromethylumbelliferyl glycosides were shown to be substrates for glycosidases. Some of them were cleaved even better than the corresponding methylumbelliferyl glycosides. 4-Trifluoromethylumbelliferyl glycosides were applied for revealing the corresponding enzyme deficiencies upon diagnosis of Gaucher and Hurler diseases as well as GM1 gangliosidosis and alpha-mannosidosis. 4-Trifluoromethylumbelliferone released after enzymatic hydrolysis of 4-trifluoromethylumbelliferyl glycosides exhibits more contrast yellow fluorescence in UV-light than the blue one of methylumbelliferone upon exposure of enzyme activity on solid supports. Therefore 4-trifluoromethylumbelliferyl glycosides are convenient substrates for revealing glycosidase activity directly in tissue samples, e.g. in placenta, and thus for fast prenatal diagnosis of lysosomal diseases. PMID:1781792

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

    PubMed Central

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

    2015-01-01

    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

  14. A Langmuir monolayer study of the action of phospholipase A2 on model phospholipid and mixed phospholipid-GM1 ganglioside membranes.

    PubMed

    Schulte, Wiebke; Orlof, Monika; Brand, Izabella; Korchowiec, Beata; Rogalska, Ewa

    2014-04-01

    Polarization-modulation infrared reflection-absorption spectroscopy, surface pressure measurements and thermodynamic analysis were used to study enzymatic hydrolysis of lipid monolayers at the air/water interface. The Ca(2+)-requiring pork pancreatic phospholipase A2 was used as a catalyst. The substrates were pure 1,2-dilauroyl-sn-glycero-3-phosphocholine or mixed 1,2-dilauroyl-sn-glycero-3-phosphocholine - monosialotetrahexosylganglioside Langmuir films. The physicochemical properties of the monolayers were established with the aim of a correlation with enzyme activity. The infrared spectra were acquired upon the advancement of the catalysis; the latter was studied at a controlled surface pressure and area of the film. Changes of the intensity and frequency of different infrared signals characteristic for the two lipids were correlated with modification of the properties of the monolayer due to hydrolysis. The amide I signal characteristic for peptides permitted detecting the enzyme adsorbed at the interface. The thermodynamic and infrared results indicate that monosialotetrahexosylganglioside increases H-bonding of the lipid polar heads in the films. This effect, which may be responsible for the low activity of phospholipase A2 in the mixed films, could be used for developing enzyme-resistant lipid systems. PMID:24524938

  15. Patient monitoring.

    PubMed

    Morton, A

    1976-11-01

    Optimum results are obtained in the care of the critically ill patient if efforts are directed to maintaining the internal environment in a state as near normal as possible. This cannot be done without the use of basic monitoring procedures. Complex investigations may have a legitmate and necessary role as research tools. There is, however, a real risk of complex procedures becoming an end in themselves in general intensive therapy units, where they are apt to distract overworked nurses and medical attendants from the care of their patients. It is important, therfore, for clearcut indications for various monitoring procedures to be defined, and in this paper an attempt has been made to outline alogical approach to the monitoring of critically ill genral surgical patients admitted intensive therapy units. PMID:1071552

  16. Patient Monitoring

    NASA Technical Reports Server (NTRS)

    1978-01-01

    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.

  17. Refugee patients.

    PubMed

    Valeras, Aimee Burke

    2016-06-01

    This short story focuses on refugee patients. Family members talk about the horrific struggles of civil war, refugee camps, and promises of US resettlement. Their harsh reception into a brutal world includes unemployment, food scarcity, and isolation. (PsycINFO Database Record PMID:27270253

  18. Patient Rights

    MedlinePlus

    ... your health care provider must give you the information you need to make a decision. Many hospitals have patient advocates who can help you if you have problems. Many states have an ombudsman office for problems with long term care. Your state's department of health may also be able to help.

  19. Patient Advocate Foundation

    MedlinePlus

    ... The Process is Simple. Patient Advocate Foundation's Patient Services provides patients with arbitration, mediation and negotiation to settle issues ... the following to learn more about how PAF Patient Services may assist you: Specialized Patient Programs Co-Pay ...

  20. Increased catabolism and decreased unsaturation of ganglioside in patients with inflammatory bowel disease

    PubMed Central

    Miklavcic, John J; Hart, Tasha DL; Lees, Gordon M; Shoemaker, Glen K; Schnabl, Kareena L; Larsen, Bodil MK; Bathe, Oliver F; Thomson, Alan BR; Mazurak, Vera C; Clandinin, M Tom

    2015-01-01

    AIM: To investigate whether accelerated catabolism of ganglioside and decreased ganglioside content contribute to the etiology of pro-inflammatory intestinal disease. METHODS: Intestinal mucosa from terminal ileum or colon was obtained from patients with ulcerative colitis or inflammatory Crohn’s disease (n = 11) undergoing bowel resection and compared to control samples of normal intestine from patients with benign colon polyps (n = 6) and colorectal cancer (n = 12) in this observational case-control study. Gangliosides and phospholipids of intestinal mucosa were characterized by class and ceramide or fatty acid composition using liquid chromatography triple-quad mass spectrometry. Content and composition of ganglioside classes GM1, GM3, GD3, GD1a, GT1 and GT3 were compared among subject groups. Content and composition of phospholipid classes phosphatidylcholine (PC) and phosphatidylethanolamine were compared among subject groups. Unsaturation index of individual ganglioside and phospholipid classes was computed and compared among subject groups. Ganglioside catabolism enzymes beta-hexosaminidase A (HEXA) and sialidase-3 (NEU3) were measured in intestinal mucosa using western blot and compared among subject groups. RESULTS: Relative GM3 ganglioside content was 2-fold higher (P < 0.05) in intestine from patients with inflammatory bowel disease (IBD) compared to control intestine. The quantity of GM3 and ratio of GM3/GD3 was also higher in IBD intestine than control tissue (P < 0.05). Control intestine exhibited 3-fold higher (P < 0.01) relative GD1a ganglioside content than IBD intestine. GD3 and GD1a species of ganglioside containing three unsaturated bonds were present in control intestine, but were not detected in IBD intestine. The relative content of PC containing more than two unsaturated bonds was 30% lower in IBD intestine than control intestine (P < 0.05). The relative content of HEXA in IBD intestine was increased 1.7-fold (P < 0.05) and NEU3 was

  1. Communicating with patients

    MedlinePlus

    ... patient. Be careful not to make assumptions. Patient teaching based on incorrect assumptions may not be very ... information you receive can help guide your patient teaching. Ask the right questions. Ask if the patient ...

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

    PubMed

    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

    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

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

    PubMed Central

    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

    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

  4. [Structural basis for β-galactosidase associated with lysosomal disease].

    PubMed

    Shimizu, Toshiyuki

    2013-01-01

    G(M1)-gangliosidosis and Morquio B are rare lysosomal storage diseases associated with a neurodegenerative disorder or dwarfism and skeletal abnormalities, respectively. These diseases are caused by deficiencies in the lysosomal enzyme human β-D-galactosidase (h-β-GAL), which lead to accumulations of the h-β-GAL substrates, G(M1) ganglioside and keratan sulfate due to mutations in the h-β-GAL gene. H-β-GAL is an exoglycosidase that catalyzes the hydrolysis of terminal β-linked galactose residues. Here, we present the crystal structures of h-β-GAL in complex with its catalytic product galactose or with its inhibitor 1-deoxygalactonojirimycin. H-β-GAL showed a novel homodimer structure; each monomer was comprised of a catalytic TIM barrel domain followed by β-domain 1 and β-domain 2. The long loop region connecting the TIM barrel domain with β-domain 1 was responsible for the dimerization. To gain structural insight into the molecular defects of h-β-GAL in the above diseases, the disease-causing mutations were mapped onto the three-dimensional structure. Finally, the possible causes of the diseases are discussed. PMID:23649392

  5. The prevalence of nine genetic disorders in a dog population from Belgium, the Netherlands and Germany.

    PubMed

    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

    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

  6. Patient-centered Radiology.

    PubMed

    Itri, Jason N

    2015-10-01

    Patient-centered care (ie, care organized around the patient) is a model in which health care providers partner with patients and families to identify and satisfy patients' needs and preferences. In this model, providers respect patients' values and preferences, address their emotional and social needs, and involve them and their families in decision making. Radiologists have traditionally been characterized as "doctor-to-doctor" consultants who are distanced from patients and work within a culture that does not value patient centeredness. As medicine becomes more patient driven and the trajectory of health care is toward increasing patient self-reliance, radiologists must change the perception that they are merely consultants and become more active participants in patient care by embracing greater patient interaction. The traditional business model for radiology practices, which devalues interaction between patients and radiologists, must be transformed into a patient-centered model in which radiologists are reintegrated into direct patient care and imaging processes are reorganized around patients' needs and preferences. Expanding radiology's core assets to include direct patient care may be the most effective deterrent to the threat of commoditization. As the assault on the growth of Medicare spending continues, with medical imaging as a highly visible target, radiologists must adapt to the changing landscape by focusing on their most important consumer: the patient. This may yield substantial benefits in the form of improved quality and patient safety, reduced costs, higher-value care, improved patient outcomes, and greater patient and provider satisfaction. PMID:26466190

  7. Counseling the Coronary Patient

    ERIC Educational Resources Information Center

    Semmler, Caryl; Semmler, Maynard

    1974-01-01

    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)

  8. [Symptomatic calcification in the newborn. Phenocopies of chondrodysplasia punctata].

    PubMed

    Leicher-Düber, A; Schumacher, R; Spranger, J

    1990-04-01

    Stippled epiphyses occur in the new-born and young infant in the different hereditary forms of chondrodysplasia punctata. Symptomatic stippling has been described also in association with chromosomal anomalies, gangliosidosis and drug induced embryopathies. We present patients with Cumarin-embryopathy (2), fetal alcohol syndrome (1), Zellweger-syndrome (2) and chromosomal anomaly 16 (1) and discuss the typical roentgenographic features, distribution and differential diagnosis of epiphyseal stippling. PMID:2160110

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

    PubMed

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

    2010-09-01

    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

  10. [Ambulatory surgery. Patients and patient education].

    PubMed

    Bredland, T; Duesund, R

    1996-02-20

    This article reviews the concept of day surgery and shows how the treatment can be organized pre-, per- and post-operatively. It can be established in a hospital-integrated unit, a unit separate from the hospital, but connected with it, or a satellite ambulatory facility. Because the patient spends only a short time in hospital it is necessary to have structured preparations before admission, for the benefit of both patient and staff. It should be easy to identify patients suitable for day surgery from the waiting lists, and preparations should be directed at treatment by day surgery right from the start. Rules must be worked out for selecting patients, as well as guidelines for information to patients. It is also necessary to plan the operation programme, and to agree how nurses and doctors should take care of the patient during the different steps of treatment. PMID:8658453

  11. Immunoglobulin G heavy chain (Gm) allotypes in multiple sclerosis.

    PubMed Central

    Pandey, J P; Goust, J M; Salier, J P; Fudenberg, H H

    1981-01-01

    Serum samples from 70 Caucasian patients with multiple sclerosis were typed for nine Gm markers. Significant association was found with the Gm 1,17;21 phenotype, and the relative risk for individuals with this phenotype was calculated at 3.6. The data indicate that Caucasians positive for Gm 1,17;21 are almost four times more likely to develop multiple sclerosis than those without this phenotype. PMID:6787085

  12. Immunoglobulin G heavy chain (Gm) allotypes in multiple sclerosis.

    PubMed

    Pandey, J P; Goust, J M; Salier, J P; Fudenberg, H H

    1981-06-01

    Serum samples from 70 Caucasian patients with multiple sclerosis were typed for nine Gm markers. Significant association was found with the Gm 1,17;21 phenotype, and the relative risk for individuals with this phenotype was calculated at 3.6. The data indicate that Caucasians positive for Gm 1,17;21 are almost four times more likely to develop multiple sclerosis than those without this phenotype. PMID:6787085

  13. Periprocedural Patient Care.

    PubMed

    Kohi, Maureen P; Fidelman, Nicholas; Behr, Spencer; Taylor, Andrew G; Kolli, Kanti; Conrad, Miles; Hwang, Gloria; Weinstein, Stefanie

    2015-10-01

    Periprocedural care of patients who undergo image-guided interventions is a task of monumental importance. As physicians who perform procedures, radiologists rely on their noninterpretive skills to optimize patient care. At the center of periprocedural care is proper patient identification. It is imperative to perform the indicated procedure for the correct patient. It is also of great importance to discuss with the patient the nature of the procedure. This conversation should include the indications, risks, benefits, alternatives, and potential complications of the procedure. Once the patient agrees to the procedure and grants informed consent, it is imperative to stop and confirm that the correct procedure is being performed on the correct patient. This universal time-out policy helps decrease errors and improves patient care. To optimize our interpretative and procedural skills, it may be necessary to provide the patient with sedation or anesthesia. However, it is important to understand the continuum of sedation and be able to appropriately monitor the patient and manage the sedation in these patients. To minimize the risks of infection, periprocedural care of patients relies on aseptic or, at times, sterile techniques. Before the procedure, it is important to evaluate the patient's coagulation parameters and bleeding risks and correct the coagulopathy, if needed. During the procedure, the patient's blood pressure and at times the patient's glucose levels will also require monitoring and management. After the procedure, patients must be observed in a recovery unit and deemed safe for discharge. The fundamental components of periprocedural care necessary to enhance patient safety, satisfaction, and care are reviewed to familiarize the reader with the important noninterpretive skills necessary to optimize periprocedural care. PMID:26466184

  14. Burns in diabetic patients

    PubMed Central

    Maghsoudi, Hemmat; Aghamohammadzadeh, Naser; Khalili, Nasim

    2008-01-01

    CONTEXT AND AIMS: Diabetic burn patients comprise a significant population in burn centers. The purpose of this study was to determine the demographic characteristics of diabetic burn patients. MATERIALS AND METHODS: Prospective data were collected on 94 diabetic burn patients between March 20, 2000 and March 20, 2006. Of 3062 burns patients, 94 (3.1%) had diabetes; these patients were compared with 2968 nondiabetic patients with burns. Statistical analysis was performed using the statistical analysis software SPSS 10.05. Differences between the two groups were evaluated using Student's t-test and the chi square test. P < 0.05 was considered as significant. RESULTS: The major mechanism of injury for the diabetic patients was scalding and flame burns, as was also the case in the nondiabetic burn patients. The diabetic burn patients were significantly older, with a lower percentage of total burn surface area (TBSA) than the nondiabetic burn population. There was significant difference between the diabetic and nondiabetic patients in terms of frequency of infection. No difference in mortality rate between diabetic and nondiabetic burn patients was observed. The most common organism in diabetic and nondiabetic burn patients was methicillin-resistant staphylococcus. Increasing %TBSA burn and the presence of inhalation injury are significantly associated with increased mortality following burn injury. CONCLUSIONS: Diabetics have a higher propensity for infection. Education for diabetic patients must include caution about potential burn mishaps and the complications that may ensue from burns. PMID:19902035

  15. Individualizing patient education for greater patient satisfaction.

    PubMed

    Alagheband, Sharzad J; Miller, Jeffrey J; Clarke, Jennie T

    2015-05-01

    The benefits of educational intervention on health outcomes has been widely discussed, but the most educational methods have not been addressed. We sought to assess preferred modes of education during an outpatient dermatology visit (ie, verbal instruction [VI], written instruction [WI], demonstration [DM], Internet resources [IR]). We secondarily looked at patient satisfaction with the educational methods used. The results indicate the most preferred method of education among 157 patients who completed a 12-question survey and areas where physicians may need to improve patient education. PMID:26057507

  16. Repositioning the Patient:

    PubMed Central

    Mold, Alex

    2013-01-01

    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

  17. [Patient education of hepatitis].

    PubMed

    Boyer, Dominique; Faillebin, Françoise; de la Brière, Aice

    2013-11-01

    The therapeutic education of patients with hepatitis C helps to improve their health and quality of life. The aim is to encourage compliance with the treatment and the fight against side effects, through to the patient's recovery. PMID:24409616

  18. Patient Eye Examinations - Adults

    MedlinePlus

    ... Examinations, Adults Patient Eye Examinations, Children Refractive Errors Scientists in the Laboratory Visual Acuity Testing Patient Eye Examinations, Adults × Warning message Automatic fallback to the cURL connection method kicked in to handle the request. Result code ...

  19. Evolution of patient navigation.

    PubMed

    Shockney, Lillie D

    2010-08-01

    The role of nurses in patient navigation has evolved over more than four decades. Navigators in cancer care can guide patients through the physical, emotional, and financial challenges that come with a diagnosis of cancer and facilitate communication among healthcare providers. Navigation has the potential to improve patient outcomes and system efficiency. Oncology nurses are well suited to help patients with cancer navigate the healthcare system from diagnosis and treatment through survivorship and palliative care. PMID:20682496

  20. Patients Provide Recommendations for Improving Patient Satisfaction.

    PubMed

    Moore, Angelo D; Hamilton, Jill B; Krusel, Jessica L; Moore, LeeAntoinette G; Pierre-Louis, Bosny J

    2016-04-01

    National Committee for Quality Assurance recommends patient-centered medical homes incorporate input from patient populations; however, many health care organizations do not. This qualitative study used two open-ended questions from 148 active duty Army Soldiers and their family members to illicit recommendations for primary care providers and clinic leadership that would improve their health care experiences. Content analysis and descriptive statistics were used to analyze responses. Participant responses were related to four major themes: Access to Care, Interpersonal Interaction, Satisfaction of Care, and Quality of Care. Participants were overall satisfied with their care; however, spending less time waiting for appointments and to see the provider or specialist were the most frequently requested improvements related to Access to Care. For Interpersonal Interaction, 82% of the responses recommended that providers be more attentive listeners, courteous, patient, caring, and respectful. Decreasing wait times and improving interpersonal skills would improve health care experiences and patient satisfaction. PMID:27046182

  1. Surveying young patients.

    PubMed

    Foster, Theresa; Maillardet, Victoria

    2010-03-01

    The East of England Ambulance Service NHS Trust (the Trust) was keen to engage young patients and to encourage them to give feedback about the service they had received. The standard Trust satisfaction survey was modified for use with young patients, and this had the effect of increasing the response rate from this patient group by 8%, and increasing the percentage of young patients aged 5-10 years completing the survey themselves by 29%. The vast majority of parents/guardians were happy for the Trust to survey their child, but the age of the child affected to whom they would like the survey sent. The Trust subsequently altered patient survey practice to write to parents/guardians of patients aged <12 years and directly to all patients aged > or = 12 years. PMID:20304894

  2. Patient-centered Care.

    PubMed

    Reynolds, April

    2009-01-01

    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

  3. Melanoma in Immunosuppressed Patients

    PubMed Central

    Kubica, Agnieszka W.; Brewer, Jerry D.

    2012-01-01

    The immunogenic characteristics of malignant melanoma are intriguing. To date, multiple studies exist regarding the immunogenicity of melanoma. In this article, we summarize data in the literature on the role of immunosuppression in melanoma and discuss several immunocompromised patient populations in detail. A comprehensive PubMed search was conducted with no date limitation. The following search terms were used: melanoma in combination with immunosuppression, immunocompromised, genetics, antigen processing, UV radiation, organ transplantation, organ transplant recipients, lymphoproliferative disease, lymphoma, CLL, NHL, radiation, and HIV/AIDS. Although no formal criteria were used for inclusion of studies, most pertinent studies on the topic were reviewed, with the exception of smaller case reports and case series. The included studies were generally large (≥1000 patients in organ transplant recipient studies; ≥500 patients in lymphoma studies), with a focus on institutional experiences, or population-based national or international epidemiologic studies. Melanoma-induced immunosuppression, the role of UV radiation in melanoma development, and the epidemiology, clinical course, and prognosis of melanoma in immunocompromised patients are highlighted. Organ transplant recipients, patients with lymphoproliferative disorders, patients with iatrogenic immunosuppression, and patients with human immunodeficiency virus infection/AIDS are also highlighted. Recommendations are proposed for the care and monitoring of immunosuppressed patients with melanoma. With better understanding of the molecular microenvironment and clinical course of melanoma in immunosuppressed patients, novel therapies could be developed and outcomes potentially affected in these patients. PMID:23036673

  4. Patient-doctor communication.

    PubMed

    Teutsch, Carol

    2003-09-01

    Communication is an important component of patient care. Traditionally, communication in medical school curricula was incorporated informally as part of rounds and faculty feedback, but without a specific or intense focus on skills of communicating per se. The reliability and consistency of this teaching method left gaps, which are currently getting increased attention from medical schools and accreditation organizations. There is also increased interest in researching patient-doctor communication and recognizing the need to teach and measure this specific clinical skill. In 1999, the Accreditation of Council for Graduate Medical Education implemented a requirement for accreditation for residency programs that focuses on "interpersonal and communications skills that result in effective information exchange and teaming with patients, their families, and other health professionals." The National Board of Medical Examiners, Federation of State Medical Boards. and the Educational Commission for Foreign Medical Graduates have proposed an examination between the. third and fourth year of medical school that "requires students to demonstrate they can gather information from patients, perform a physical examination, and communicate their findings to patients and colleagues" using standardized patients. One's efficiency and effectiveness in communication can be improved through training, but it is unlikely that any future advances will negate the need and value of compassionate and empathetic two-way communication between clinician and patient. The published literature also expresses belief in the essential role of communication. "It has long been recognized that difficulties in the effective delivery of health care can arise from problems in communication between patient and provider rather than from any failing in the technical aspects of medical care. Improvements in provider-patient communication can have beneficial effects on health outcomes". A systematic review of

  5. [Two patients with mumps].

    PubMed

    van Brummelen, S E; de Vries, E; Schneeberger, P M; van Binnendijk, R S; Lestrade, P; Wever, P C

    2006-08-01

    Two patients, men aged 17 and 19 years respectively, were admitted with parotitis epidemica and orchitis caused by mumps. The second patient also had meningitis. PCR analysis revealed that, in both cases, the causative agentwas a mumps virus that was genetically related to a wild-type virus responsible for an outbreak in Singapore. This viral strain was also responsible for a mumps outbreak at Hotel School The Hague in September 2004. Both patients were not fully vaccinated. Both patients were from regions in which clustering of patients with clinical signs of mumps has been seen. Interestingly, a number of patients with confirmed mumps had been fully vaccinated. Possible explanations for the increase in mumps cases include low vaccination and immunity levels, primary and secondary vaccine failure and the emergence of genetically disparate mumps viruses. PMID:16924947

  6. Patient Education: An Annotated Bibliography.

    ERIC Educational Resources Information Center

    Simmons, Jeannette

    Topics included in this annotated bibliography on patient education are (1) background on development of patient education programs, (2) patient education interventions, (3) references for health professionals, and (4) research and evaluation in patient education. (TA)

  7. Physicians as Patient Teachers

    PubMed Central

    Brunton, Stephen A.

    1984-01-01

    Physicians have a central role in educating patients and the public in the elements of personal health maintenance. To be an effective teacher, one must recognize the learning needs of each patient and use methods of information transfer that will result in comprehension and compliance. To bring about a change in life-style, one must also have an understanding of a patient's health beliefs and the determinants of human behavior. Using this information together with behavior modification strategies, physicians can forge an effective partnership with patients working toward the goal of optimum health. PMID:6395500

  8. The critically ill immunosuppressed patient

    SciTech Connect

    Parrillo, J.E.; Masur, H. )

    1987-01-01

    This book discusses the papers on the diagnosis and management of immunosuppressed patient. Some of the topics are: life-threatening organ failure in immunosuppressed patients; diagnosis and therapy of respiratory disease in the immunosuppressed patient; CNS complication of immunosuppression; infections; antineoplastic therapy of immunosuppressed patient; radiation therapy-issues in critically ill patient; AIDS; and management of bone marrow transplant patients.

  9. Patient Education Thesaurus.

    ERIC Educational Resources Information Center

    Cooper, Lynn

    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…

  10. National Patient Safety Foundation

    MedlinePlus

    ... 9/27/2016 NPSF Professional Learning Series Webcast: Health Literacy: Improving Patient Understanding 9/29/2016 Certified Professional in Patient Safety Review Course Webinar 10/4/2016 NPSF Webcast: Implementing RCA2: Lessons from the Trenches: Aurora Health ... In Remember Me Forgot your password? ...

  11. Patient Education in Thyrotoxicosis.

    ERIC Educational Resources Information Center

    Lincoln, N. B.; Sturrock, N. D. C.; Sowter, H.; Abbott-Harland, S.; Nichols, E.; Jeffcoate, W. J.

    2000-01-01

    Study aims to assess the need for a thyrotoxicosis patient education programs and evaluates a group education session. Patients with thyrotoxicosis were surveyed to assess their needs. Determined that people with thyrotoxicosis had limited knowledge about their condition. The offer of a group education program has little effect on that knowledge…

  12. Communicating with patients.

    PubMed

    Kaplowitz, G J

    1999-01-01

    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

  13. Five things patients want.

    PubMed

    Camahort, Elisa

    2006-01-01

    Many in the healthcare industry think it's inevitable that we're heading toward consumer-directed healthcare (CDHC). For CDHC to work, it will require more of a partnership between doctors and patients than ever before. The author offers key ways doctors and their staffs can respect the time and intelligence of their partners in health--their patients. PMID:16711095

  14. A Patient Assessment Guide

    ERIC Educational Resources Information Center

    Fuller, Dorothy; Rosenaur, Janet Allan

    1974-01-01

    Use of a nursing assessment/patient history tool developed by project faculty at the school of nursing, University of California, San Francisco and used in a primary care clinic assisted nursing students in collecting patient information, making home visits, functioning as team members, recording data, and in defining their nursing role. (EA)

  15. Caring for transgender patients.

    PubMed

    Abebe, Alyssa

    2016-06-01

    Clinicians need a better understanding of transgender populations and a systematic approach to treating transgender patients medically and psychologically while managing any potential judgment or bias. This article explains key concepts, describes transgender patient health concerns, and discusses how to perform a comprehensive history. PMID:27228044

  16. The Patient as Teacher.

    ERIC Educational Resources Information Center

    Weisser, Roland J.; Medio, Franklin J.

    1985-01-01

    A program of seminars designed to explore student perceptions of the emotional and psychological aspects of physician-patient interactions, part of a clinical diagnosis course, used graduate medical students to act as patients in videotaped interviews, interview evaluations, and lectures and demonstrations on interpersonal communication skills.…

  17. Measuring improved patient choice.

    PubMed

    Holmes-Rovner, M; Rovner, D R

    2000-08-01

    Patient decision support (PDS) tools or decision aids have been developed as adjuncts to the clinical encounter. Their aim is to support evidence-based patient choice. Clinical trials of PDS tools have used an array of outcome measures to determine efficacy, including knowledge, satisfaction, health status and consistency between patient choice and values. This paper proposes that the correlation between 'subjective expected utility' (SEU) and decision may be the best primary endpoint for trials. SEU is a measure usually used in behavioural decision theory. The paper first describes how decision support tools may use decision analysis to structure the presentation of evidence and guide patient decision-making. Uses of expected utility (EU) are suggested for evaluating PDS tools when improving population health status is the objective. SEU is the theoretically better measure when internal consistency of patient choices is the objective. PMID:11083037

  18. Issues with dying patients.

    PubMed

    Valent, P

    1978-04-22

    Doctors have the privilege of looking after patients from the moment of birth to the moment of death. Yet, the holistic approach to patients is interfered with by the doctor's role as a warrior against death, where death's everpresent claim on our lives, and its final victory, are ignored. This paper attempts to explore why doctors are in their current position, the mechanisms for ignoring death which are shared by doctors and patients, the nature of the fear of death, and practical implications for the treatment of dying patients. More and more patients die now in medical settings. It is incumbent on doctors to understand the dying process, if much unnecessary suffering is to be prevented. PMID:661717

  19. Doctor-patient relationship

    PubMed Central

    Chamsi-Pasha, Hassan; Albar, Mohammed A.

    2016-01-01

    The doctor-patient relationship is an intricate concept in which patients voluntarily approach a doctor and become part of a contract by which they tend to abide by doctor’s instructions. Over recent decades, this relationship has changed dramatically due to privatization and commercialization of the health sector. A review of the relevant literature in the database of MEDLINE published in English between 1966 and August 2015 was performed with the following keywords: doctor-patient relationship, physician-patient relationship, ethics, and Islam. The Muslim doctor should be familiar with the Islamic teachings on the daily issues faced in his/her practice and the relationship with his/her patients. PMID:26837392

  20. [Physiotherapy of cancer patients].

    PubMed

    Gomez, Izabella; Szekanecz, Éva; Szekanecz, Zoltán; Bender, Tamás

    2016-07-01

    Physiotherapy of cancer patients is one of the most controversial issues in our country. Malignant diseases are firstly mentioned as a contraindication of physiotherapy. Until now, physiotherapy was not suggested (or only in limited accessibility) for those patients who had malignant disease in medical history. International medical practice was less restrictive in managing this topic. The development of imaging techniques put this question in a new light. On the basis of evidence, the majority of articles have reported beneficial effects of physiotherapy in cancer patients, and only few articles mentioned it as harmful. Of course, each patient requires an individual assessment, however, if we exclude the possibility of tumor recurrence and metastasis, most of physiotherapy procedures can be used safely. One of the aims of this review is to support the physicians' decisions when to prescribe treatments, in such a way, that more patients could receive physiotherapy. Orv. Hetil., 2016, 157(31), 1224-1231. PMID:27476518

  1. Approach to bleeding patient

    PubMed Central

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

    2014-01-01

    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

  2. Patients living with disabilities

    PubMed Central

    Lofters, Aisha; Guilcher, Sara; Maulkhan, Niraj; Milligan, James; Lee, Joseph

    2016-01-01

    Objective To compare the potential risk factors for lower-quality primary care, the potential markers of unmet needs in primary care, and the willingness to participate in future research among primary care patients with versus without physical disabilities. Design A waiting room survey using a convenience sample. Setting A family health team (FHT) in Kitchener-Waterloo, Ont, with a designated Mobility Clinic. Participants A total of 40 patients seen at the FHT Mobility Clinic and 80 patients from the general patient population of the same FHT. Main outcome measures Socioeconomic status and social capital, number of self-reported emergency department visits and hospitalizations in the preceding year, and willingness of the patients in the 2 groups to participate in future research studies. Results Patients from the Mobility Clinic were more than twice as likely to be receiving benefits or social assistance (75.0% vs 32.1%, P < .001), were twice as likely to report an annual household income of less than $40000 (58.6% vs 29.2%, P = .006), and were more likely to report their health status to be fair or poor (42.5% vs 16.2%, P = .002). Half of Mobility Clinic patients had visited the emergency department at least once in the preceding year, compared with 29.7% in the general patient population (P = .027). When asked if they would be willing to provide their health card number in the future so that it could be linked to health care data for research, 82.5% of Mobility Clinic patients agreed versus 55.0% of those in the general patient population (P = .004). Conclusion In this study, patients with disabilities were at a social disadvantage compared with their peers without disabilities and were more likely to use the emergency department, suggesting that they had unmet health needs. Future research should continue to explore this patient population and to investigate if an interprofessional primary health care team approach focused on patients with disabilities can

  3. Nutrition in dialysis patients.

    PubMed

    Sen, D; Prakash, J

    2000-07-01

    Malnutrition is a common clinical problem in dialysis patients, which is multifactorial in origin. It is most often found in a patient of chronic renal failure (CRF) during the period when the glomerular filtration rate (GFR) falls below 10 ml/min, but dialysis is yet to be started. The loss of proteins, aminoacids and other essential nutrients during the procedure of dialysis may further aggravate the malnutrition. Poor nutrition in dialysis patients is associated with increased morbidity and mortality in the form of delayed wound healing, malaise, fatigue, increased susceptibility to infection and poor rehabilitation. In view of the above consequences, all patients on dialysis must undergo nutritional assessment. It is very vital to maintain good nutritional status in-patients on dialysis by adequate protein and calories intake, appropriate supplementation of iron, calcium, minerals and water-soluble vitamins and, of course, the supplementation should be individualised. Nutritional needs are enhanced in presence of stresses like infection or surgery to limit excessive tissue catabolism and therefore, these are the situations, which demand intensive nutrition therapy. Total parenteral nutrition (TPN) may be required for patients on dialysis in intensive care unit, using a central venous catheter. However, enteral route is always preferred to parenteral ones, whenever possible. Even after adequate dialysis has been given, dietary counselling is often required for both hemodialysis and peritoneal dialysis patients to ensure that they ingest the recommended amount of protein, calories and essential micronutrients. PMID:11273510

  4. Do patients have duties?

    PubMed Central

    Evans, H M

    2007-01-01

    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

  5. The medically compromised patient.

    PubMed

    Parnell, A G

    1986-06-01

    Diabetes mellitus is found in up to 5 per cent of the population. There is an excess of blood sugar due to a deficiency or diminished effectiveness of insulin. It is a complex disease which, if not controlled, has many major complications including an increased incidence of heart attacks, strokes and vascular changes in many other organs. The management of young onset diabetic patients is directed towards: controlling the carbohydrate intake, testing the blood sugar by the patient and regular insulin injections. Great care must be taken in treating diabetics in the dental surgery. Except for children, any diabetic can be treated for simple dental procedures by ensuring freedom from pain, by eliminating stress and by ensuring that the patient does not miss a meal. Children, unstable diabetic patients and those with infections or requiring multiple extractions should be treated in hospital under the care of an endocrinologist. In hypertension it is only after a number of years that complications begin to appear. The main ones are those of stroke, retinal haemorrhages, renal failure and heart disease. Dentists should be encouraged to take the blood pressure of all adults who present for treatment. Patients with increased blood pressure yet controlled by drugs may be treated as normal patients. Those that are not well controlled should be referred to their physician. Dental appointments must be free of pain and stress should be avoided. A screening method is presented which assists in the evaluation of medically compromised patients. PMID:2941377

  6. Respecting patient confidentiality.

    PubMed

    Price, Bob

    2015-02-01

    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

  7. Doctors and patients.

    PubMed

    Gillon, R

    1986-02-15

    Gillon outlines some prima facie moral duties of physicians to patients that have emerged from his previous articles in a series on philosophical medical ethics. These duties follow from four general ethical principles--respect for autonomy, beneficence, non-maleficence, and justice--plus the self-imposed supererogatory duty of medical beneficence. From these principles the author derives such duties as providing adequate information and advice on treatment options, encouraging patient participation leading to informed decisions, maintaining competence and exposing incompetence, admitting errors, disclosing personal medico-moral standards, and acknowledging that other interests may occasionally supersede those of the individual patient. Gillon concludes that, where self interest conflicts with medical beneficence, the claim of medicine as a profession requires that the patient's interests take priority. PMID:3081128

  8. Why make people patients?

    PubMed Central

    Marinker, Marshall

    1975-01-01

    People confront their doctors with three modes of unhealth - disease, illness and sickness. Each is discussed, and the question is asked and answered as to why in this situation people wish to become patients. PMID:1177270

  9. Psychiatric patient and anaesthesia

    PubMed Central

    Attri, Joginder Pal; Bala, Neeru; Chatrath, Veena

    2012-01-01

    Many patients with psychiatric illnesses are prescribed long-term drug treatment, and the anaesthesiologist must be aware of potential interactions with anaesthetic agents. Psychotropic drugs often given in combination with each other or with other non-psychiatric drugs generally exert profound effects on the central and peripheral neurotransmitter and ionic mechanisms. Hence, prior intake of these drugs is an important consideration in the management of the patient about to undergo anaesthesia and surgery. This article highlights the effects of anaesthetics on patients taking antipsychotics, tricyclic antidepressants, monoamine oxidase inhibitors and lithium carbonate. The risk that should be considered in the perioperative period are the extent of surgery, the patient's physical state, anaesthesia, the direct and indirect effects of psychotropics, risk of withdrawal symptoms and risk of psychiatric recurrence and relapse. PMID:22529413

  10. Appendicitis in mature patients.

    PubMed Central

    Burns, R P; Cochran, J L; Russell, W L; Bard, R M

    1985-01-01

    All patients greater than 50 years of age (N = 96) admitted with a pre- or postoperative diagnosis of acute appendicitis from 1971 to 1980 were reviewed. A comparative series of 91 patients aged 25 to 50 years was similarly reviewed. Noninflammatory diseases of the appendix and incidental appendectomies were excluded. Detailed study of symptoms, clinical presentation, laboratory evaluation, radiographic evaluation, concomitant diseases, hospital course, surgical findings, complications, and mortality were completed. Comparison of patients aged 25 to 50 to patients older than 50 years revealed a statistically significant increased incidence of perforation in the older group (p less than 0.0001). Sixty-five per cent of the older group showed greater incidence of perforation. Further analysis of this series yields the hypothesis that the increased incidence of perforation is related to a significant decrease in the frequency of classic presentation in the greater-than-50 age group, a significant decrease in frequency of correct admission diagnosis and a significant delay between admission and surgical procedure in the older group. A more rapid pathophysiologic progression of appendicitis with increasing age was noted. A much higher percentage of older patients was undiagnosed until the surgical procedure. In this group, there was a longer duration of symptoms, less frequent classic presentation, and decreased frequency of right lower quadrant guarding and tenderness as compared to patients with correct diagnosis prior to surgery. Complications were much more frequent in older patients and higher still in those with perforation. Analysis of findings by decade of life revealed an anticipated high incidence of perforated appendicitis in patients greater than 50, but also showed a continuation of the high incidence of perforation into the decade 40 to 50. There were three deaths in the entire study group (1.6%) all occurring in the older age group with postoperative

  11. [Patients' Rights Act].

    PubMed

    Haier, A J

    2016-09-01

    The new Patients' Rights Act does not reflect rights of patients as professional obligations of physicians for the first time. It adopted common longtime jurisdiction, but in some respects it is going beyond. This law clearly extended the documentation requirements of physicians, especially concerning the extent of documentation. In surgical fields the requirements for enlightening physicians were more strongly worded than in previous jurisdiction. In medical facilities it is now mandatory to establish an internal quality management system. PMID:27626814

  12. Depression in dialysis patients.

    PubMed

    King-Wing Ma, Terry; Kam-Tao Li, Philip

    2016-08-01

    Depression is the most common psychiatric illness in patients with end-stage renal disease (ESRD). The reported prevalence of depression in dialysis population varied from 22.8% (interview-based diagnosis) to 39.3% (self- or clinician-administered rating scales). Such differences were attributed to the overlapping symptoms of uraemia and depression. Systemic review and meta-analysis of observational studies showed that depression was a significant predictor of mortality in dialysis population. The optimal screening tool for depression in dialysis patients remains uncertain. The Beck Depression Inventory (BDI), Patient Health Questionnaire (PHQ) and Center for Epidemiologic Studies Depression Scale (CESD) have been validated for screening purposes. Patients who scored ≥14 using BDI should be referred to a psychiatrist for early evaluation. Structured Clinical Interview for DSM disorders (SCID) remains the gold standard for diagnosis. Non-pharmacological treatment options include cognitive behavioural therapy and exercise training programs. Although frequent haemodialysis may have beneficial effects on patients' physical and mental well-being, it cannot and should not be viewed as a treatment of depression. Selective serotonin reuptake inhibitors (SSRIs) are generally effective and safe in ESRD patients, but most studies were small, non-randomized and uncontrolled. The European Renal Best Practice (ERBP) guideline suggests a trial of SSRI for 8 to 12 weeks in dialysis patients who have moderate-major depression. The treatment effect should be re-evaluated after 12 weeks to avoid prolonging ineffective medication. This review will discuss the current understanding in the diagnosis and management of depression in dialysis patients. PMID:26860073

  13. Restraining potentially violent patients.

    PubMed

    Splawn, G

    1991-10-01

    People who are emotionally distraught or mentally ill are rarely predictable. A calm, reassuring, but firm and decisive manner is most effective in dealing with out-of-control patients. Staff members should be careful to never position themselves with a potentially violent or distraught patient between them and the door. A room should be emptied of all extraneous, potentially dangerous objects before restraint of a patient. A clear plan of what is to be done and who is to do what is necessary. All staff members should remove glasses, pens, scissors, and other items that are potential weapons before restraining a patient. A humane attitude when restraining patients is extremely important. Sometimes the attitude of those applying restraints can be more traumatic than the actual application of the restraints. It is important that staff members remember that patients who need restraint are not "bad" people. For whatever reason, they have lost the ability to control themselves. These people do not like being out of control; given a choice, they would choose not to be. The staff attitude during this stressful event, which is becoming all too common in the emergency department, can have a tremendous effect on patients who require this procedure. When a patient is restrained in a competent, humane manner, staff members can pride themselves on their skills in dealing successfully with this emergency, just as they can when dealing with a cardiac arrest. Finally, it has been said that you cannot truly understand what another person is going through until you have had the same experience yourself.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1921070

  14. [Patient safety: Glossary].

    PubMed

    Sabio Paz, Verónica; Panattieri, Néstor D; Cristina Godio, Farmacéutica; Ratto, María E; Arpí, Lucrecia; Dackiewicz, Nora

    2015-10-01

    Patient safety and quality of care has become a challenge for health systems. Health care is an increasingly complex and risky activity, as it represents a combination of human, technological and organizational processes. It is necessary, therefore, to take effective actions to reduce the adverse events and mitigate its impact. This glossary is a local adaptation of key terms and concepts from the international bibliographic sources. The aim is providing a common language for assessing patient safety processes and compare them. PMID:26294153

  15. Patient care in radiography

    SciTech Connect

    Ehrlich, R.A.; McCloskey, E.D.

    1989-01-01

    This book focuses on patient care procedures for radiographers. The authors focus on the role of the radiographer as a member of the health care team. The authors report on such topics as communication in patient care: safety, medico-legal considerations, transfer and positioning; physical needs; infection control; medication; CPR standards, acute situations; examination of the GI tract; contrast media; special imaging techniques and bedside radiography.

  16. Keeping the patient happy.

    PubMed

    Bomar, F

    1992-01-01

    Customer service is the catch word for the 90s and hospitals are constantly looking for ways to make their customer--the patient--happier. In a section of the country where fried chicken, grits and gravy are home-cooking staples, an unlikely marriage between Southern hospitals and a European food preparation process may be the key to many hospitals' ability to cater to the patient by offering gourmet meals on a regular basis. PMID:10120396

  17. White coat, patient gown.

    PubMed

    Wellbery, Caroline; Chan, Melissa

    2014-12-01

    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

  18. [Urosepsis in Geriatric Patients].

    PubMed

    Heppner, H J; Yapan, F; Wiedemann, A

    2016-02-01

    Due to the demographic shift, increasing numbers of geriatric patients are admitted to acute care hospitals of all levels of care. This means that special challenges must be met in the medical care and management of these patients.Immunosenescence and multimorbidity make elderly patients vulnerable to infectious diseases. Urinary tract infections range from "simple" cystitis to pyelonephritis and urosepsis and, at 25%, are the second most common form of infection in geriatric patients. It is often difficult to make a diagnosis because typical symptoms do not always occur. Urosepsis, a hyperactive and uncontrolled immune response of the organism due to exogenous damage, is based on bacterial infection of the urogenital tract. Urinary retention, immunosuppressive medication, malignancy, diabetes mellitus and renal or prostatic processes promote the risk for urosepsis. Complicated urosepsis additionally comprises a structural or functional abnormality, including ureteral obstruction. Risk factors for urosepsis are urinary incontinence, an indwelling urinary catheter, hydronephrosis or ureteral calculi. Patients suffering from diabetes mellitus are also at a higher risk for urosepsis. When diagnosing elderly patients, one has to consider that the classic symptoms can be masked by multimorbidity, or septic encephalopathy and acute confusion (delirium) may be the only symptoms. Body temperature is lower in elderly patients and does not necessarily rise to 38°C or more in the acute phase. In patients older than 75 years who are suspicious for sepsis, temperatures as low as 37.4°C should be rated as fever. Treatment of urosepsis basically includes clearing the focus, antimicrobial treatment, stabilisation of circulation and replacement of failed organ functions. Initial empiric antibiotic treatment, depending on local resistance, should be done with acylaminopenicilline and beta-lactamase inhibitors (e. g. piperacillin/combactam or tazobactam or group 3 cephalosporins

  19. The patient's view.

    PubMed

    Rachagan, S S; Sharon, K

    2003-03-01

    The medical practitioner has always had to juggle several roles. First and foremost, the doctor is a healer, a provider of curative services. Second, he is an examiner, an assessor of the patient's health status. Third, he is a researcher, always trying to push the boundaries of medical knowledge. Fourth, he is a rationer of services, he decides how best to apportion the limited resources at his disposal. Traditionally, the patient-doctor relationship has been largely exclusive in nature and the doctor would quite comfortably slip in and out of these roles, his focus centred on his patient's interests. In this era of large corporate health care providers, multi-billion-biotechnology industry, mammoth pharmaceutical companies, medical insurance schemes and international trade instruments, it has become increasingly difficult for the doctor to juggle these four roles. He is constantly subjected to conflicting demands. Patients' interests do not always come first anymore and patients are beginning to realise this. They no longer trust the medical profession unreservedly. There has been steady erosion of the patient-doctor relationship most clearly evidenced by the rising tide of litigation against doctors. There needs to be a reappraisal of these roles that the doctor plays. The conflicts must be recognised and addressed. Patients need to be informed and their interests must be protected if the doctor-patient relationship is to be restored. Medical malpractice suits are on the increase. The tort system as it exists is failing both doctors and patients. The question we must ask is what are patients looking for when they sue doctors? Most of the time they need compensation for the injuries suffered. Sometimes they are looking for accountability, they want the doctor to be punished in some way. Sometimes they merely want to air their grievances and know that they are heard. The current system more often than not takes too long to compensate, the process is a gamble and

  20. Plastic Surgery for Ethnic Patients

    MedlinePlus

    ... Briefing Papers > Plastic Surgery for Ethnic Patients Briefing Paper: Plastic Surgery for Ethnic Patients More than 3. ... 2067-2071. Share Related Links Plastic Surgery Briefing Papers Menu Cosmetic Reconstructive Patient Safety Before & After Find ...

  1. Choosing effective patient education materials

    MedlinePlus

    ... to overcome a fear before being open to teaching. Respect the patient's limits. Offer the patient only ... deliver patient education. Examples include one-on-one teaching, demonstrations, and analogies or word pictures to explain ...

  2. 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 ...

  3. Endoscopy in the obese patient.

    PubMed

    Schreiner, Mitchal A; Fennerty, M Brian

    2010-03-01

    Obese patients present many unique challenges to the endoscopist. Special consideration should be given to these patients, and endoscopists need to be aware of the additional challenges that may be present while performing endoscopic procedures on obese patients. This article reviews the special risks that obese patients face while undergoing endoscopy, endoscopic management of patients postbariatric surgery, and future role of endoscopy in the management of obese patients. PMID:20202582

  4. Mastocytosis among elderly patients

    PubMed Central

    Rouet, Audrey; Aouba, Achille; Damaj, Gandhi; Soucié, Erinn; Hanssens, Katia; Chandesris, Marie-Olivia; Livideanu, Cristina Bulai; Dutertre, Marine; Durieu, Isabelle; Grandpeix-Guyodo, Catherine; Barète, Stéphane; Bachmeyer, Claude; Soria, Angèle; Frenzel, Laurent; Fain, Olivier; Grosbois, Bernard; de Gennes, Christian; Hamidou, Mohamed; Arlet, Jean-Benoit; Launay, David; Lavigne, Christian; Arock, Michel; Lortholary, Olivier; Dubreuil, Patrice; Hermine, Olivier; Georgin-Lavialle, Sophie

    2016-01-01

    Abstract Mastocytosis is a heterogeneous group of diseases with a young median age at diagnosis. Usually indolent and self-limited in childhood, the disease can exhibit aggressive progression in mid-adulthood. Our objectives were to describe the characteristics of the disease when diagnosed among elderly patients, for which rare data are available. The French Reference Center conducted a retrospective multicenter study on 53 patients with mastocytosis >69 years of age, to describe their clinical, biological, and genetic features. The median age of our cohort of patients was 75 years. Mastocytosis variants included were cutaneous (n = 1), indolent systemic (n = 5), aggressive systemic (n = 11), associated with a hematological non-mast cell disease (n = 34), and mast cell leukemia (n = 2). Clinical manifestations were predominantly mast cell activation symptoms (75.5%), poor performance status (50.9%), hepatosplenomegaly (50.9%), skin involvement (49.1%), osteoporosis (47.2%), and portal hypertension and ascites (26.4%). The main biological features were anemia (79.2%), thrombocytopenia (50.9%), leucopenia (20.8%), and liver enzyme abnormalities (32.1%). Of the 40 patients tested, 34 (85%), 2 (5%), and 4 (10%) exhibited the KIT D816V mutant, other KIT mutations and the wild-type form of the KIT gene, respectively. Additional sequencing detected significant genetic defects in 17 of 26 (65.3%) of the patients with associated hematological non-mast cell disease, including TET2, SRSF2, IDH2, and ASLX1 mutations. Death occurred in 19 (35.8%) patients, within a median delay of 9 months, despite the different treatment options available. Mastocytosis among elderly patients has a challenging early detection, rare skin involvement, and/or limited skin disease; it is heterogeneous and has often an aggressive presentation with nonfortuitous associated myeloid lineage malignant clones, and thus a poor overall prognosis. PMID:27310990

  5. Transporting Forensic Psychiatric Patients.

    PubMed

    Dike, Charles C; Nicholson, Elizabeth; Young, John L

    2015-12-01

    Patients in a forensic psychiatric facility often require escorted transport to medical facilities for investigations or treatments of physical health ailments. Transporting these patients presents significant safety and custody challenges because of the nature of patients housed in forensic psychiatric facilities. A significant proportion of these patients may be transfers from the Department of Corrections (DOC) under legal mandates for psychiatric evaluation and treatment better provided in a hospital setting, and most of them will return to the DOC. Although departments of correction have protocols for escorting these potentially dangerous individuals, it is unclear whether receiving psychiatric hospitals have established procedures for maintaining the safety of others and custody of these individuals during transportation outside the hospital facility. The literature is sparse on precautions to be observed when transporting dangerous forensic psychiatric patients, including those with high escape risk. In this article, we describe one forensic inpatient facility's procedure for determining the appropriate level needed to transport these individuals outside of the forensic facility. We also describe the risk assessment procedure for determining level of transport. These are quality improvement measures resulting from a critical review of an incident of escape from the forensic facility several years ago. PMID:26668224

  6. Patient access innovations: integrating patients within the system of care.

    PubMed

    Marino, Daniel J; Faber, William; Duncan, Meredith

    2015-12-01

    Clinically integrated networks seeking to ensure in-network access and strengthen patient engagement should adopt five strategic areas of focus: Extend access beyond traditional models. Manage out-migration. Make it easy for patients to stay in the network. Build patient engagement into clinical care models. Explore innovative methods to engage patients. PMID:26793943

  7. Perinatal Patient Safety Project

    PubMed Central

    Nunes, Julie; McFerran, Sharon

    2005-01-01

    The Perinatal Patient Safety Project (PPSP) was created as a systemic strategy for creating high-reliability perinatal units by preventing identified causes of perinatal events in the clinical setting. With developmental funding from a Garfield grant, implementation of the PPSP has been completed at four pilot sites in the Kaiser Permanente Northern California (KPNC) Region. Its success has resulted in implementation at all perinatal units in the KPNC Region as well as being promoted by National Risk Management for nationwide implementation. PPSP emphasizes structured communication, multidisciplinary rounds, a definition of fetal well-being, and practicing for emergencies. Steps taken to create high reliability perinatal care include improved communication, patient safety focus, and satisfaction among perinatal patients, providers, and staff. PMID:21660157

  8. [Respecting patient intimacy].

    PubMed

    2014-04-01

    Transparency as a general rule for all our professional acts casts doubts about the statement of the Hippocratic Oath that says "Whatever I see or hear in the lives of my patients, I will keep secret, as considering all such things to be private". Medical secrecy protects the intimacy of patients, who reveal to their physicians their most hidden secrets aiming to recover their health. Therefore, physicians should receive those secrets with reverence and care, as servers and not as their owners. The values associated with the respect for personal intimacy are the anthropological basis of medical confidentiality. A medical act is performed by definition between two equally honorable individuals. Therefore, the professional honors the trust of his patient, maintaining strict confidence of what is revealed. Therefore, medical secrecy must be strengthened rather than weakened, pursuing common wealth and dignity. PMID:25117042

  9. [Toxoplasmosis in immunocompromised patients].

    PubMed

    Machala, L; Kodym, P; Malý, M; Geleneky, M; Beran, O; Jilich, D

    2015-06-01

    In humans, toxoplasmosis mostly occurs as a latent infection, but in immunocompromised individuals, the agent may reactivate and cause severe to life-threatening disease. HIV positive individuals and transplant recipients, in particular hematopoietic stem cell transplant and heart transplant recipients, are at highest risk. The disease most often affects the central nervous system but can involve any organ. Because of the alteration of the immune response in these patients, the serodiagnosis is not reliable and direct detection of the causative agent is needed--namely by microscopy and DNA PCR. If inadequately treated or left untreated, toxoplasmosis generally has a fatal prognosis in immunocompromised patients and therefore, the treatment must be started as early and energetically as possible. The gold standard both in the treatment of reactivation and secondary prophylaxis is the pyrimethamine-sulfadiazine combination while co-trimoxazole can be used in the primary prophylaxis for high-risk patients. PMID:26099608

  10. Patient Portals: An Underused Resource for Improving Patient Engagement.

    PubMed

    Tulu, Bengisu; Trudel, John; Strong, Diane M; Johnson, Sharon A; Sundaresan, Devi; Garber, Lawrence

    2016-01-01

    The potential of patient portals to improve patient engagement and health outcomes has been discussed for more than a decade. The slow growth in patient portal adoption rates among patients and providers in the United States, despite external incentives, indicates that this is a complex issue. We examined evidence of patient portal use and effects with a focus on the pulmonary domain. We found a paucity of studies of patient portal use in pulmonary practice, and highlight gaps for future research. We also report on the experience of a pulmonary department using a patient portal to highlight the potential of these systems. PMID:26066707

  11. Three patients with arteritis.

    PubMed

    Eke, F; Balfe, J W; Hardy, B E

    1984-09-01

    Three boys were treated for arteritis of the aorta and great vessels and bilateral renal artery stenosis. One presented at age 6 months with failure to thrive, excessive sweating, and vomiting: hypertension and cardiac failure were subsequently diagnosed. The two older boys (7 and 14 years) presented with symptomless hypertension. The clinical and angiographic findings in the three patients suggest that the illness may have been Takayasu's arteritis, which should be included in the differential diagnosis of hypertension in infancy and childhood. Renal autotransplantation was performed in all three patients with good results. Early renal autotransplantation may reduce the morbidity associated with this disease. PMID:6148918

  12. Constructions of the patient in healthcare communications: six patient figures.

    PubMed

    Pors, Anja Svejgaard

    2016-04-11

    Purpose - The purpose of this paper is to examine how strategic, patient-centred communication plays a part in the discursive management of expectations posed to patients and healthcare organizations. Design/methodology/approach - The paper provides an analysis of four documents collected as part of an ethnographic case study regarding "The Perspective of the Patient" - a Danish Hospital's patient-centred communication programme. Mapping methods inspired by Grounded Theory are used to qualify the analysis. Findings - The paper shows that strategic patient-centred communication addresses both a care-oriented approach to the patient and deploys market perceptions of patients. Market and care is seen as co-existing organizing modes that entail expectations to the patient. In the communication programme the patient is constructed in six information-seeking patient figures: affective patient; target group patient; citizen with rights; patient as a competent resource; user as active partner; and consumer. As a result, the patient-centred communication programme renders the patient as a flexible figure able to fit organizational demands of both care orientation and market concerns. Originality/value - This study contributes to qualitative research in organizational health communication by combining two subfields - patient-centredness and health communication - in an empirical study of how market and care are intertwined in a patient-centred communication programme. The argument goes beyond the prevalent prescriptive approaches to patient-centredness and healthcare communication, instead providing a critical analytical perspective on strategic communication and patient-centredness and showing how expectations are posed to both patient and organization. PMID:27052626

  13. A nursing challenge: adult-onset Tay-Sachs disease.

    PubMed

    Hamilton, D

    1991-12-01

    Adult-onset GM2 gangliosidosis (AOG), also labelled Adult-Onset Tay-Sachs disease, is a slowly progressing disease caused by a gradual accumulation of the GM2 ganglioside in neurons due to defective hexosaminidase A. Recent research findings and clinical experiences suggest that AOG may be more widespread than previously believed. Moreover, the diagnosis of AOG is often delayed because patients present with psychotic symptoms that mimic dementia, schizophrenia, mania, and depression. Because AOG patients typically respond poorly to psychiatric drug therapy and the symptomatology is so diverse, nurses must design and implement nursing care that ensures safety, structure, and comfort. PMID:1759864

  14. Hospital Patients Are Adult Learners.

    ERIC Educational Resources Information Center

    Caffarella, Rosemary S.

    Patient education is recognized by health care providers and patients themselves as an important component of adequate health care for hospital patients. Through this informational process, patients receive information about specific health problems, learn the necessary competencies to deal with them, and develop accepting attitudes toward the…

  15. Patient Education Strategies in Dermatology

    PubMed Central

    Holder, Jessica L.

    2009-01-01

    Patient education is an important aspect of patient care in dermatology. Successful education increases patient satisfaction and results in improved outcomes and adherence. This article discusses the role of patient education in dermatology. Specifically, Part I of the review examines evidence demonstrating the benefits of patient education and recognizes the challenges that limit effective patient education. These challenges can be summarized as barriers to understanding, poor patient recall, conflicting information, and barriers to physician delivery. Further descriptions and an assessment of these limitations along with methods to combat them are included in the review. PMID:20725581

  16. Insomnia in cancer patients.

    PubMed

    O'Donnell, Joseph F

    2004-01-01

    Insomnia affects up to 50% of patients with cancer, but has received little attention from the oncology community compared with other symptoms such as pain and fatigue. Insomnia and subsequent sleep disturbances can lead to fatigue, mood disturbances, and contribute to immunosuppression, which can have a profound impact on quality of life and perhaps affect the course of disease. Insomnia in cancer patients must be distinguished from cancer-related fatigue. Although they are 2 distinct conditions, insomnia and fatigue are interrelated. Insomnia often leads to daytime fatigue that interferes with normal functioning. Conversely, daytime fatigue can lead to behaviors such as napping, which result in insomnia. The primary goal of insomnia treatment should first be to relieve any underlying disorder (eg, cancer pain, depression, anxiety) that may be causing the sleep disturbance. Because insomnia in this patient population may be due to a variety of causes, treatment must be multimodal and include both pharmacologic and nonpharmacologic therapies. A plan that combines attention to sleep hygiene and cognitive-behavioral therapy with prescription of hypnotic medications can help relieve the symptoms of insomnia in cancer patients and improve their quality of life. PMID:15675652

  17. Discharging older patients.

    PubMed

    2016-09-01

    Significant numbers of older people with dementia use general hospital services, and ensuring the safe and appropriate discharge home of patients with poor cognition, impaired judgement, misperception or reduced risk awareness is complex and challenging for many healthcare professionals. PMID:27615354

  18. [Healthcare patient loyalty].

    PubMed

    Ameri, Cinzia; Fiorini, Fulvio

    2016-01-01

    If the "old economy" preached standardization of products/services in order to reduce costs, the "new economy" is based on the recognition of the needs and the management of information. It is aimed at providing better and more usable services. One scenario is a national health service with regional management but based on competition between hospitals/companies.This led to a different handling of the user/patient, which has become the center of the health system: marketing seeks to retain the patient, trying to push a client-patient to not change their healthcare service provider. In costs terms, it is more economical to retain a customer rather than acquire a new one: a satisfied customer is also the best sounding board for each company. Customer equity is the management of relations with patients which can result in a greater customer value: it is possible to recognize an equity of the value, of the brand and of the report. Loyalty uses various marketing activities (basic, responsive, responsible, proactive and collaborative): each hospital/company chooses different actions depending on how many resources it plans to invest in loyalty. PMID:27374397

  19. The Adolescent Patient.

    ERIC Educational Resources Information Center

    Daniel, William A., Jr.

    Written to orient the physician and paramedical personnel to the adolescent patient, the book provides information concerning the changes of adolescence, and age-related problems and illnesses. Part 1 discusses the essence of adolescence by describing physical, mental, and emotional growth and development. Part 2, the major section, consists of 21…

  20. [Aphasia in elderly patients].

    PubMed

    Moreaud, Olivier; David, Danielle; Brutti-Mairesse, Marie-Pierre; Debray, Matthieu; Mémin, Armelle

    2010-03-01

    Aphasia is common in elderly patients in the context of vascular or neurodegenerative disorders. In some cases, aphasia is an isolated symptom, occurring suddenly after a stroke, or developing progressively as a primary progressive aphasia. The diagnosis and treatment are then very similar in older and younger patients. Therapy may be more complicated because of the high prevalence, in older patients, of associated non linguistic symptoms (attentional and dysexecutive symptoms, behavioral and psychological symptoms or sensorial deficits), fatigability, and comprehension deficits. It may then become very difficult to recognize aphasia among all these disorders and to appreciate the physiopathology. A complete evaluation of language, cognitive functions, psychopathology, and behavior is very helpful, as are neuroimaging techniques (MRI is the most relevant). A good knowledge of classical aphasic pictures associated with stroke, Alzheimer disease or related disorders, is highly recommended. Rehabilitation must be proposed even for older patients, so far as aphasia alters the communication abilities. It must be kept in mind that associated symptoms may limit considerably the therapy. PMID:20215098

  1. Teleophthalmology: improving patient outcomes?

    PubMed

    Sreelatha, Omana Kesary; Ramesh, Sathyamangalam VenkataSubbu

    2016-01-01

    Teleophthalmology is gaining importance as an effective eye care delivery modality worldwide. In many developing countries, teleophthalmology is being utilized to provide quality eye care to the underserved urban population and the unserved remote rural population. Over the years, technological innovations have led to improvement in evidence and teleophthalmology has evolved from a research tool to a clinical tool. The majority of the current teleophthalmology services concentrate on patient screening and appropriate referral to experts. Specialty care using teleophthalmology services for the pediatric group includes screening as well as providing timely care for retinopathy of prematurity (ROP). Among geriatric eye diseases, specialty teleophthalmology care is focused toward screening and referral for diabetic retinopathy (DR), glaucoma, age-related macular degeneration (ARMD), and other sight-threatening conditions. Comprehensive vision screening and refractive error services are generally covered as part of most of the teleophthalmology methods. Over the past decades, outcome assessment of health care system includes patients' assessments on their health, care, and services they receive. Outcomes, by and large, remain the ultimate validators of the effectiveness and quality of medical care. Teleophthalmology produces the same desired clinical outcome as the traditional system. Remote portals allow specialists to provide care over a larger region, thereby improving health outcomes and increasing accessibility of specialty care to a larger population. A high satisfaction level and acceptance is reported in the majority of the studies because of increased accessibility and reduced traveling cost and time. Considering the improved quality of patient care and patient satisfaction reported for these telemedicine services, this review explores how teleophthalmology helps to improve patient outcomes. PMID:26929592

  2. [Patients' University, illness and learning].

    PubMed

    Tourette-Turgis, Catherine

    2015-10-01

    The Patients' University, a pilot project at the Université Pierre et Marie Curie, in Paris, enables patients-experts to follow a degree program in patient therapeutic education (University Diploma and Master). Recently, graduate patients and patients directly concerned proposed to co-create a new university certificate for treatment pathway coordinators for breast cancer, rounding out the 120-hour university certificate program on healthcare democracy and meeting the recommendations of the new cancer plan. PMID:26455618

  3. Training Patient and Family Storytellers and Patient and Family Faculty

    PubMed Central

    Morrise, Lisa; Stevens, Katy Jo

    2013-01-01

    Narrative medicine has become a prominent method of developing more empathetic relationships between medical clinicians and patients, on the basis of a deeper understanding of the patient experience. Beyond its usefulness during clinical encounters, patient storytelling can inform processes and procedures in Advisory Councils, Committee Meetings, and Family as Faculty settings, leading to improved quality and safety in health care. Armed with a better understanding of the patient experience, clinicians and administrators can make decisions, hopefully in collaboration with patients, that will enrich the patient experience and increase satisfaction among patients, families, and staff. Patient and family storytelling is a key component of the collaboration that is ideal when an organization seeks to deliver patient- and family-centered care. Providing patients and families with training will make the narratives they share more powerful. Health care organizations will find that purposeful storytelling can be an invaluable aspect of a patient- and family-centered culture. Well-delivered storytelling will support quality- and safety-improvement efforts and contribute to improved patient satisfaction. This article provides instruction for teaching patients and families how to tell stories with purpose and offers advice about how to support patients, families, and clinicians participating in this effort. PMID:24355906

  4. Lysosomal Multienzyme Complex: Pros and Cons of Working Together

    PubMed Central

    Bonten, Erik J.; Annunziata, Ida; d’Azzo, Alessandra

    2014-01-01

    The ubiquitous distribution of lysosomes and their heterogeneous protein composition reflects the versatility of these organelles in maintaining cell homeostasis and their importance in tissue differentiation and remodeling. In lysosomes, the degradation of complex, macromolecular substrates requires the synergistic action of multiple hydrolases that usually work in a stepwise fashion. This catalytic machinery explains the existence of lysosomal enzyme complexes that can be dynamically assembled and disassembled to efficiently and quickly adapt to the pool of substrates to be processed or degraded, adding extra tiers to the regulation of the individual protein components. An example of such a complex is the one composed of three hydrolases that are ubiquitously but differentially expressed: the serine carboxypeptidase, Protective Protein/Cathepsin A (PPCA), the sialidase, Neuraminidase-1 (NEU1), and the glycosidase β-Galactosidase (β-GAL). Next to this ‘core’ complex, the existence of sub-complexes, that may contain additional components, and function at the cell surface or extracellularly, suggests as yet unexplored functions of these enzymes. Here we review how studies of basic biological processes in the mouse models of three lysosomal storage disorders, galactosialidosis, sialidosis, and GM1-gangliosidosis, revealed new and unexpected roles for the three respective affected enzymes, Ppca, Neu1 and β-Gal, that go beyond their canonical degradative activities. These findings have broadened our perspective on their functions and may pave the way for the development of new therapies for these lysosomal storage disorders. PMID:24337808

  5. [Patient-reported and patient-weighted outcomes in ophthalmology].

    PubMed

    Scheibler, F; Finger, R P; Grosselfinger, R; Dintsios, C-M

    2010-03-01

    Considering patients' values and preferences in comparative effectiveness research (CER) is one of the main challenges in ophthalmology (value-based medicine). This article defines core terms in CER. The concept of patient-relevant (or patient-important) outcomes is distinguished from patient-reported outcomes (PRO) by means of examples in the field of ophthalmology. In order to be able to give a consistant recommendation if an intervention leads to conflicting results for different outcomes (trade-off), a ranking of outcomes will be necessary. Examples of studies in glaucoma patients are provided that demonstrate the possibilities of ranking of outcomes based on patient preferences. PMID:20024566

  6. Patient (customer) expectations in hospitals.

    PubMed

    Bostan, Sedat; Acuner, Taner; Yilmaz, Gökhan

    2007-06-01

    The expectations of patient are one of the determining factors of healthcare service. The purpose of this study is to measure the Patients' Expectations, based on Patient's Rights. This study was done with Likert-Survey in Trabzon population. The analyses showed that the level of the expectations of the patient was high on the factor of receiving information and at an acceptable level on the other factors. Statistical meaningfulness was determined between age, sex, education, health insurance, and the income of the family and the expectations of the patients (p<0.05). According to this study, the current legal regulations have higher standards than the expectations of the patients. The reason that the satisfaction of the patients high level is interpreted due to the fact that the level of the expectation is low. It is suggested that the educational and public awareness studies on the patients' rights must be done in order to increase the expectations of the patients. PMID:17028043

  7. Gastric Cancer in Young Patients

    PubMed Central

    Dhobi, Manzoor A.; Wani, Khursheed Alam; Parray, Fazl Qadir; Wani, Rouf A.; Peer, G. Q.; Abdullah, Safiya; Wani, Imtiyaz A.; Wani, Muneer A.; Shah, Mubashir A.; Thakur, Natasha

    2013-01-01

    Aim. The aim of this study was to see the clinical, pathological, and demographic profile of young patients with stomach carcinoma besides association with p53. Patients and Methods. Prospective study of young patients with stomach carcinoma from January 2005 to December 2009. A total of 50 patients with age less than 40 years were studied. Results. Male female ratio was 1 : 1.08 in young patients and 2.5 : 1 in older patients. A positive family history of stomach cancer in the first degree relatives was present in 10% of young patients. Resection was possible only in 50% young patients. 26% young patients underwent only palliative gastrojejunostomy. The most common operation was lower partial gastrectomy in 68%. Amongst the intraoperative findings peritoneal metastasis was seen in 17.4% in young patients. 50% young patients presented in stage IV as per AJCC classification (P value .004; sig.). None of the patients presented as stage 1 disease in young group. Conclusion. Early detection of stomach carcinoma is very important in all patients but in young patients it is of paramount importance. PMID:24381753

  8. Melanoma in Black Patients

    PubMed Central

    Smith, Robert J.

    1982-01-01

    Melanoma in black patients is uncommon but not rare. This paper reports six cases seen in one general surgeon's practice in Arkansas during a 14-year period. A review of the current literature regarding melanoma in blacks is given. Characteristically, melanoma in blacks is found on the soles of the feet, palms of the hands, or mucous membranes. The tumor has a deadly potential unless it is treated at an early stage; four of the patients reported have died of metastatic disease. A public health program is needed to make physicians and the public aware of the incidence and location of this tumor. ImagesFigure 1Figure 2Figure 3Figure 4 PMID:7120473

  9. Evaluating respiratory patient disability.

    PubMed

    Ruiz Manzano, Juan; Alfageme Michavila, Inmaculada; Chiner Vives, Eusebi; Martínez González, Cristina

    2012-08-01

    The evaluation of the disabilities of patients with respiratory disease is regulated by the Spanish Ministry of Labor and Social Security, as are disabilities of any other type. We believe, however, that in respiratory pathologies this evaluation is especially complicated because, as they are chronic processes, they inter-relate with other systems. Furthermore, they tend to have occasional exacerbations; therefore, normal periods may alternate with other periods of important functional limitations. The present document arises from the desire of SEPAR to update this topic and to respond to the requests of respiratory disease patient associations who have asked us to do so. In this paper, we analyze the current situation of work disability legislation as well as the determination of degrees and percentages, including the current criteria for assigning disabilities due to respiratory tract deficiencies. Lastly, we propose work guidelines that would improve the existing scenario and outline this evaluation for specific pathologies. PMID:22341300

  10. Patient with inoperable pheochromocytoma

    PubMed Central

    Brancíková, D.; Mechl, Z.; Adam, Z.; Jandáková, E.; Pavlovský, Z.; Válek, V.; Andrašina, Z.

    2015-01-01

    Malignant pheochromocytoma is a tumour with a very low incidence that occurs sporadically or in the presence of multiple endocrine neoplasia. We present the case of a woman with a sporadic occurrence of pheochromocytoma diagnosed in the phase of multiple dissemination in the abdominal cavity and overexpressing adrenaline, noradrenaline, and dopamine. Local transarterial chemoembolization and systemic treatment with lanreotide resulted in a very good response, a decrease in the production of catecholamines for 12 months and a partial decrease for another 8 months, with stabilization of disease determined by imaging. Systemic treatment with tegafur resulted in disease stabilization lasting 50 months, after which the drug was discontinued because of adverse effects. Maintenance therapy with lanreotide continues, and no disease progression has been observed for 4 months. The treatment algorithm for such patients is multidisciplinary and must always take into account the current scope of the disease, intercurrence, and the general condition of the patient. PMID:26089731

  11. Patient with inoperable pheochromocytoma.

    PubMed

    Brancíková, D; Mechl, Z; Adam, Z; Jandáková, E; Pavlovský, Z; Válek, V; Andrašina, Z

    2015-06-01

    Malignant pheochromocytoma is a tumour with a very low incidence that occurs sporadically or in the presence of multiple endocrine neoplasia. We present the case of a woman with a sporadic occurrence of pheochromocytoma diagnosed in the phase of multiple dissemination in the abdominal cavity and overexpressing adrenaline, noradrenaline, and dopamine. Local transarterial chemoembolization and systemic treatment with lanreotide resulted in a very good response, a decrease in the production of catecholamines for 12 months and a partial decrease for another 8 months, with stabilization of disease determined by imaging. Systemic treatment with tegafur resulted in disease stabilization lasting 50 months, after which the drug was discontinued because of adverse effects. Maintenance therapy with lanreotide continues, and no disease progression has been observed for 4 months. The treatment algorithm for such patients is multidisciplinary and must always take into account the current scope of the disease, intercurrence, and the general condition of the patient. PMID:26089731

  12. Visualising patient flow.

    PubMed

    Jensen, Andrew; Boyle, Justin; Khanna, Sankalp

    2012-01-01

    We describe the development of a method to distil routinely collected clinical data into patient flow information to aid hospital bed management. Using data from state-wide emergency department and inpatient clinical information systems, a user-friendly interface was developed to visualise patient flow conditions for a particular hospital. The historical snapshots employ a variable time scale, allowing flow to be visualised across a day, week, month or year. Flow information includes occupancy, arrival and departure rates, length-of-stay and access block observations, which can be filtered by age, departure status, diagnosis, elective status, triage category, and admission unit. The tool may be helpful in supporting hospital bed managers in their daily decision making. PMID:22797023

  13. Mucormycosis in immunochallenged patients

    PubMed Central

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

    2008-01-01

    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

  14. Teleophthalmology: improving patient outcomes?

    PubMed Central

    Sreelatha, Omana Kesary; Ramesh, Sathyamangalam VenkataSubbu

    2016-01-01

    Teleophthalmology is gaining importance as an effective eye care delivery modality worldwide. In many developing countries, teleophthalmology is being utilized to provide quality eye care to the underserved urban population and the unserved remote rural population. Over the years, technological innovations have led to improvement in evidence and teleophthalmology has evolved from a research tool to a clinical tool. The majority of the current teleophthalmology services concentrate on patient screening and appropriate referral to experts. Specialty care using teleophthalmology services for the pediatric group includes screening as well as providing timely care for retinopathy of prematurity (ROP). Among geriatric eye diseases, specialty teleophthalmology care is focused toward screening and referral for diabetic retinopathy (DR), glaucoma, age-related macular degeneration (ARMD), and other sight-threatening conditions. Comprehensive vision screening and refractive error services are generally covered as part of most of the teleophthalmology methods. Over the past decades, outcome assessment of health care system includes patients’ assessments on their health, care, and services they receive. Outcomes, by and large, remain the ultimate validators of the effectiveness and quality of medical care. Teleophthalmology produces the same desired clinical outcome as the traditional system. Remote portals allow specialists to provide care over a larger region, thereby improving health outcomes and increasing accessibility of specialty care to a larger population. A high satisfaction level and acceptance is reported in the majority of the studies because of increased accessibility and reduced traveling cost and time. Considering the improved quality of patient care and patient satisfaction reported for these telemedicine services, this review explores how teleophthalmology helps to improve patient outcomes. PMID:26929592

  15. Patient Safety in Surgery

    PubMed Central

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

    2006-01-01

    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 (α = 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

  16. "The impatient patient".

    PubMed

    Bos, Lodewijk; Carroll, Denis; Marsh, Andy

    2008-01-01

    Modern Healthcare Systems that have embraced ICT and Internet technologies (referred to as Health 1.0) are evolving towards self management but from a clinical knowledge perspective. In contrast, from a user experience perspective, and using the latest web 2.0 technologies, the developing healthcare social networking communities (referred to as Health 2.0) are evolving towards becoming online medical portals. The growing Grand Challenge for healthcare is therefore: how will health care services (Health 1.0) work together with user-generated health care (Health 2.0) in a consumer market place delivering self management services for a healthier lifestyle and medical compliance. What is foreseen is that the self care information tool of the future will be a combination between the patient's observation record and the Internet, with the doctor and the patient positioned together at the intersection but not having to pay attention to the technology. This article deals with various aspects related to this Grand Challenge like the paradigm shift towards a needs-led and consumer-oriented healthcare, the role, supply and quality of information and the changing doctor-patient relationship. PMID:18560062

  17. Trusting patients, trusting nurses.

    PubMed

    Sellman, Derek

    2007-01-01

    The general expectation that patients should be willing to trust nurses is rarely explored or challenged despite claims of diminishing public trust in social and professional institutions. Everyday meanings of trust take account of circumstance and suggest that our understanding of what it means to trust is contextually bound. However, in the context of health care, to trust implies a particular understanding which becomes apparent when abuses of this trust are reported and acknowledged as scandals. The predominant assumption in the literature that trust is something that occurs between equally competent adults cannot explain trust in nursing precisely because of the unequal power relationships between patients on the one hand and healthcare professionals on the other. Moreover, the tendency to conflate terms such as trust, reliance, confidence and so on suggests that confusion permeates discussions of trust in nursing. In this paper, I argue in support of Annette Baier's requirement of good will (or lack of ill will) as the essential feature of trust, and outline how this account (i) enables us to make the necessary distinctions between trust on the one hand and 'trust pretenders' on the other; and (ii) lays the foundations for understanding trust in relationships, such as those between patients and nurses, where power differentials exist. PMID:17238998

  18. Tolerability and patient compliance.

    PubMed

    Roose, S P

    1999-01-01

    Currently available antidepressants interact with several types of receptors, which may explain both wanted and unwanted effects of these drugs. These effects are different and distinctive, and knowledge about them may help clinicians understand differences between compounds in terms of their tolerability profiles. Given roughly comparable efficacy, tolerability profile is the critical determinant in selecting an antidepressant medication for a particular patient. In addition, tolerability is inseparably linked to patient compliance, both in acute and long-term treatment, and ultimately to overall success of treatment. Refinement in pharmacologic profiles of all newly introduced antidepressants resulted in overall advantages in tolerability in comparison with older tricyclic compounds. However, differences in receptor interactions between antidepressants are directly reflected in tolerability (adverse event) profiles. Among new antidepressants, mirtazapine and the selective serotonin reuptake inhibitors share favorable overall tolerability and safety, especially with respect to low premature termination rates because of adverse events, cardiac safety, and safety in overdose. However, the different pharmacologic profile of mirtazapine is reflected in its different tolerability profile. Because of interactions with the histamine (H1) receptor, mirtazapine may be related to transient initial somnolence and weight gain in some patients. Its serotonin-2 (5-HT2)-blocking properties may account for lack of sexual dysfunction, insomnia, nervousness, and agitation. Mirtazapine's 5-HT3-blocking properties are unique among all currently available antidepressants and may account for lack of gastrointestinal adverse events. PMID:10446736

  19. COPD: the patient perspective

    PubMed Central

    Jones, Paul W; Watz, Henrik; Wouters, Emiel FM; Cazzola, Mario

    2016-01-01

    Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease characterized by nonreversible airway obstruction. Well-characterized symptoms such as exertional dyspnea and fatigue have a negative impact on patients’ quality of life (QoL) and restrict physical activity in daily life. The impact of COPD symptoms on QoL is often underestimated; for example, 36% of patients who describe their symptoms as being mild-to-moderate also admit to being too breathless to leave the house. Additionally, early morning and nighttime symptoms are a particular problem. Methods are available to allow clinicians to accurately assess COPD symptoms, including patient questionnaires. Integrated approaches to COPD management, particularly pulmonary rehabilitation, are effective strategies for addressing symptoms, improving exercise capacity and, potentially, also increasing physical activity. Inhaled bronchodilators continue to be the mainstay of drug therapy in COPD, where options can be tailored to meet patients’ needs with careful selection of the inhaled medication and the device used for its delivery. Overall, an integrated approach to disease management should be considered for improving QoL and subsequent patient outcomes in COPD. PMID:26937186

  20. Analysis of Patient Service Time in Ambulatory Clinics: Patient Tracking

    PubMed Central

    Zerbe, Tony R.; Zerbe, Shirleen D.

    1990-01-01

    Historically, analysis of patient service time (patient tracking) in ambulatory clinics has been performed manually. A case study of Eye and Ear Clinic in Pittsburgh, PA, revealed that this approach to patient data collection was prone to clerical error and did not satisfy the clinic's information-processing needs. Initial attempts at automation identified the features required of a successful computerized scheduling and patient tracking system. These essential features are being designed into a prototype system using a local area network platform. The software for this system employs bar code technology to log patients' movement. The resultant data permits analysis of clinic operation and rapid response to unforseen events. Patient information is presented in a color-coded format to permit-at-a-glance comprehension of data on multiple patients (up to 76) simultaneously. A scheduling module projects patients' arrival time and ensures availability of critical resources.

  1. [Tracheostomy in pediatrics patients].

    PubMed

    Fantoni, A; Ripamonti, D

    2002-05-01

    This is a case study of 79 children who under-went a tracheostomy with three different techniques, used in succession on three different groups of patients: surgical, percutaneous with progressive probes and translaryngeal technique. The pediatric patient, only under the age of 10, starts showing clear-cut anatomical differences compared to an adult, which gradually become more marked the younger the patient is. The causes of increased difficulties that can normally be found in these patients are obviously due to the reduced diameter of the airway and, above all, the high degree of pliability of the cartilaginous frame. After the discovery that even minimal external pressure can cause the collapse of the tracheal walls, it was decided to adopt the systematic use of a rigid bronchoscope, in order to be able to offer internal support to the anterior wall. The following advantages were obtained in the various techniques: In surgery it permitted the reduction, through the protrusion of the trachea, of the size of the operatory field, of the tracheal opening and consequently of the local trauma. It also caused less bleeding and reduced the risk of lesion to the pleural dome which are very frequent when a bronchoscope is not used. In the percutaneous method the bronchoscope allowed the application of the technique without complications, even in infants of only a few months' old, because it eliminated tracheal squashing, caused by the introduction of the needle, dilators and especially cannula, and the relative danger of lesion to the posterior wall of the trachea. This complication which was always impending in the original technique, which does not involve the use of a rigid bronchoscope, is the main reason which lead to the ban on PDT for patients younger than 16-18. In the translaryngeal method the advantages are of minor importance because they are limited to the initial stage of the procedure, the introduction of the needle and guide wire which are quicker and more

  2. The challenge of patient adherence.

    PubMed

    Martin, Leslie R; Williams, Summer L; Haskard, Kelly B; Dimatteo, M Robin

    2005-09-01

    Quality healthcare outcomes depend upon patients' adherence to recommended treatment regimens. Patient nonadherence can be a pervasive threat to health and wellbeing and carry an appreciable economic burden as well. In some disease conditions, more than 40% of patients sustain significant risks by misunderstanding, forgetting, or ignoring healthcare advice. While no single intervention strategy can improve the adherence of all patients, decades of research studies agree that successful attempts to improve patient adherence depend upon a set of key factors. These include realistic assessment of patients' knowledge and understanding of the regimen, clear and effective communication between health professionals and their patients, and the nurturance of trust in the therapeutic relationship. Patients must be given the opportunity to tell the story of their unique illness experiences. Knowing the patient as a person allows the health professional to understand elements that are crucial to the patient's adherence: beliefs, attitudes, subjective norms, cultural context, social supports, and emotional health challenges, particularly depression. Physician-patient partnerships are essential when choosing amongst various therapeutic options to maximize adherence. Mutual collaboration fosters greater patient satisfaction, reduces the risks of nonadherence, and improves patients' healthcare outcomes. PMID:18360559

  3. Patterns of Physician-Patient Communication Associated with Patient Satisfaction.

    ERIC Educational Resources Information Center

    Williams, M. Lee; Clampitt, Phillip G.

    Using data drawn from ten initial physician/patient interviews, an original category system was employed to analyze patterns of physician/patient communication. Static analysis, interaction analysis, and Markov chain analysis were used to discover the underlying communication patterns associated with patient satisfaction. Results revealed that…

  4. Health literacy and patient portals.

    PubMed

    Gu, Yulong; Orr, Martin; Warren, Jim

    2015-06-01

    Health literacy has been described as the capacity to obtain, process, and understand basic health information and services needed to make appropriate health decisions. Improving health literacy may serve to promote concordance with therapy, engage patients in their own health care, and improve health outcomes. Patient portal technology aims at enabling patients and families to have easy access to key information in their own medical records and to communicate with their health care providers electronically. However, there is a gap in our understanding of how portals will improve patient outcome. The authors believe patient portal technology presents an opportunity to improve patient concordance with prescribed therapy, if adequate support is provided to equip patients (and family/carers) with the knowledge needed to utilise the health information available via the portals. Research is needed to understand what a health consumer will use patient portals for and how to support a user to realise the technology's potential. PMID:26125067

  5. Cancer Patients and Fungal Infections

    MedlinePlus

    ... mould-related diseases in immunocompromised patients. Journal of Antimicrobial Chemotherapy 2011;66:i5-i14. Ribaud P. Fungal ... al. Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: 2010 Update ...

  6. What makes a patient unhappy.

    PubMed

    Tobin, Howard A

    2008-05-01

    The best way to avoid an unhappy postoperative patient is to do everything one can to optimize the preoperative consultation and select patients carefully. This article draws on the judgment of a cosmetic surgeon with years of experience. By focusing on the individual unique needs of each patient, and by not being afraid to say no, the wise surgeon can expect a very high satisfaction rate from patients. PMID:18355697

  7. Patients and their families.

    PubMed

    Firth, P

    2006-01-01

    The focus of this chapter is on how clinicians can understand and communicate with the families of patients suffering from cancer. Most doctors and nurses do not have training in this area and are uncomfortable when conducting interviews with whole families. The need to extend our skills in the family context reflects the changes in the way care is provided to patients with a serious illness. We recognise the part families play in providing care and the subsequent effects on family life. The influence of systemic thinking and social construction theories has led to the acknowledgement that we are all part of systems which interact with each other and it is no longer appropriate to see the patient in isolation. The chapter will look at ideas from family therapy which can help us assess and intervene when necessary. The patient suffering from a life-threatening illness such as cancer looks to his family and friends for care and support. The management and course of the illness is affected by the involvement of the family and how they manage the stress and the effects of illness on a family member (Wright and Leahey 2000). Duhamel and Dupuis (2003) point out that there are three important factors in the management of the illness: the effects of family stress, the needs of the family as caregivers, and the effects of the role and how the family cope with the way the patient experiences his illness. This presents professionals working in the field with challenges they are often ill-equipped to deal with. Most healthcare workers have inadequate training in understanding family dynamics and even less knowledge about how to communicate effectively with whole families. Consequently, many healthcare professionals avoid couple and family interviews, feeling inadequate and helpless like the families themselves. I will address some of these issues in the chapter, firstly by examining what we now regard as the family and then by using ideas from systemic theory I will look at

  8. Hospital Libraries in Patient's Education.

    ERIC Educational Resources Information Center

    Iroka, Luke A.

    1988-01-01

    Reviews the positive effects of patient education, including the physician patient relationship, improvements in health status, and cost effectiveness. The status of hospital libraries in Nigeria is described, and suggestions for the implementation of patient education programs are made. (5 references) (CLB)

  9. Professional Preparation in Patient Education.

    ERIC Educational Resources Information Center

    Pigg, R. Morgan, Jr.

    Information on Indiana University's course in patient education is presented, along with sources of additional information on patient education and a summary of a national survey on professional preparation in patient education. An outline of the following course topics is presented: past and current developments, health care delivery, patient…

  10. Patient perception of wound photography.

    PubMed

    Wang, Sheila C; Anderson, John Ae; Jones, Duncan Vb; Evans, Robyn

    2016-06-01

    The objectives of this study were to provide an assessment of photographic documentation of the wound from the patients' perspective and to evaluate whether this could improve patients' understanding of and involvement in their wound care. Our results revealed that most patients visiting the wound care clinic have difficult-to-see wounds (86%). Only 20% of patients monitor their wounds and instead rely on clinic or nurse visits to track the healing progress. There was a significant association between patients' ability to see their wound and their subsequent memory of the wound's appearance. This was especially true for patients who had recently begun visiting the wound care clinic. This relationship was not present in patients who had visited the clinic for 3  or more years. Patients reported that the inability to see their wounds resulted in feeling a loss of autonomy. The majority of patients reported that photographing their wounds would help them to track the wound progress (81%) and would afford them more involvement in their own care (58%). This study provides a current representation of wound photography from the patients' perspective and reveals that it can motivate patients to become more involved in the management of their wounds - particularly for patients with difficult-to-see wounds. PMID:24872018

  11. Dysphagia in stroke patients

    PubMed Central

    Singh, S; Hamdy, S

    2006-01-01

    Swallowing musculature is asymmetrically represented in both motor cortices. Stroke affecting the hemisphere with the dominant swallowing projection results in dysphagia and clinical recovery has been correlated with compensatory changes in the previously non‐dominant, unaffected hemisphere. This asymmetric bilaterality may explain why up to half of stroke patients are dysphagic and why many will regain a safe swallow over a comparatively short period. Despite this propensity for recovery, dysphagia carries a sevenfold increased risk of aspiration pneumonia and is an independent predictor of mortality. The identification, clinical course, pathophysiology, and treatment of dysphagia after stroke are discussed in this review. PMID:16754707

  12. [Patients with sepsis].

    PubMed

    Oppert, M

    2016-05-01

    Sepsis is still the leading cause of mortality in noncardiac intensive care units. The new definition of sepsis emphasizes the importance of organ dysfunction. The Sepsis-related Organ Failure Assessment (SOFA) score is an indicator for organ dysfunction. The diagnosis of sepsis is for the most part made on clinical parameters with an altered mental status being a very sensitive indicator. Microbiological work-up is essential and two sets of blood cultures are the recommended minimum. Management includes prompt initiation of adequate antibiotic treatment and swift fluid resuscitation. Overinfusion is to be avoided as this itself can have a negative impact on patient outcome. PMID:27160262

  13. Strengthening patient-provider relationships.

    PubMed

    Wilkinson, Connie Rasmussen; Williams, Marjory

    2002-01-01

    In support of the Veterans Health Administration commitment to the promotion of shared decision-making between providers and patients, this study investigated the relationship between the provision of a patient appointment guidebook, designed to promote and support patient participation in the health care visit, and patient perceptions of primary care visit effectiveness. This study compared perceptions among 277 randomly selected patients randomly assigned to one of two groups. Patients assigned to an intervention group received a patient appointment guidebook along with the standard appointment reminder letter prior to the scheduled routine visit. Patients assigned to a control group received only the standard appointment reminder letter. Patient perceptions were assessed with a follow-up questionnaire designed to measure patient agreement with six statements pertaining to primary care visit effectiveness. No significant differences were noted in the proportion of patients in the two groups that agreed with any of the six statements pertaining to primary care visit effectiveness. Significant differences were noted, however, in the proportion of patients in the groups who received preventive health care interventions of influenza vaccination, pneumococcal vaccination, and gender-specific cancer screening. Approximately 37% of the patients in the intervention group provided positive comments about the patient appointment guidebook, while only 7% provided negative comments. Although statistically inconclusive, the narrative comments indicate that a patient appointment guidebook may assist veterans in preparing for primary care appointments. The lack of significant difference between the two groups on the measures of primary care visit effectiveness may be due, in part, to positive perceptions among the sample in general, as reflected by high levels of agreement and predominantly positive comments for both control and intervention groups. PMID:12048339

  14. The 'Patient experience' revolution.

    PubMed

    Hooten, Doug; Zavadsky, Matt

    2014-02-01

    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

  15. Patients' perspectives on pain.

    PubMed

    Norrbrink, Cecilia; Löfgren, Monika; Hunter, Judith P; Ellis, Jaqueline

    2012-01-01

    Nociceptive and neuropathic pain (NP) are common consequences following spinal cord injury (SCI), with large impact on sleep, mood, work, and quality of life. NP affects 40% to 50% of individuals with SCI and is sometimes considered the major problem following SCI. Current treatment recommendations for SCI-NP primarily focus on pharmacological strategies suggesting the use of anticonvulsant and antidepressant drugs, followed by tramadol and opioid medications. Unfortunately, these are only partly successful in relieving pain. Qualitative studies report that individuals with SCI-related long-lasting pain seek alternatives to medication due to the limited efficacy, unwanted side effects, and perceived risk of dependency. They spend time and money searching for additional treatments. Many have learned coping strategies on their own, including various forms of warmth, relaxation, massage, stretching, distraction, and physical activity. Studies indicate that many individuals with SCI are dissatisfied with their pain management and with the information given to them about their pain, and they want to know more about causes and strategies to manage pain. They express a desire to improve communication with their physicians and learn about reliable alternative sources for obtaining information about their pain and pain management. The discrepancy between treatment algorithms and patient expectations is significant. Clinicians will benefit from hearing the patient´s voice. PMID:23459087

  16. Saving our smallest patients.

    PubMed

    Lynch, Thomas F; Kugler, Liz; Niedziela, Janine

    2014-01-01

    The feedback from the staff that participated in the Full Scale Drill was overwhelmingly positive. Working and becoming acquainted with members from other supporting departments is critical to a successful evacuation. They enjoyed being a part of the drill and expressed that having ownership of an evacuation plan is vital in the care of our babies. This turned out to be a remarkable team building exercise on many levels. The planning team achieved its overall goal of creating a sense of control over a potentially chaotic environment and now believes that they could execute an evacuation for any reason with maximum protection for their patients. In a similar way various groups in and outside of the Medical Center have an understanding of the complexities of this patient group and what would be needed to effectively support their needs in a disaster. The NICU/CCN Evacuation Committee looks back over almost a year of hard work with tremendous satisfaction and renewed confidence. PMID:25181794

  17. Patient Zero”:

    PubMed Central

    McKay, Richard A.

    2014-01-01

    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

  18. [Back pain: patients versus research].

    PubMed

    Theus, Renske; Zaat, Joost O M; Uijen, Annemarie; Enzing, Joost J

    2014-01-01

    In 2008, approximately 1,559,000 Dutch patients consulted their GP because of back pain. One out of 20 back pain patients is ultimately referred to a specialist, most often to a neurologist. A smaller number (also) go to a neurosurgeon or orthopaedist. Once referred, patients often receive treatments such as pain killers or discectomy. Scientific evidence in systematic reviews is scarce for the treatments we investigated because of small patient groups and a lack of randomised research. We made an infographic to show the numbers of patients with back pain who visit their GP or a specialist. PMID:24988162

  19. Progressive Care of Obese Patients.

    PubMed

    Dambaugh, Lori A; Ecklund, Margaret M

    2016-08-01

    Obese patients have complex needs that complicate their care during hospitalization. These patients often have comorbid conditions, including hypertension, heart failure, obstructive sleep apnea, pressure ulcers, and difficulty with mobility. Obese patients may be well served in the progressive care setting because they may require more intensive nursing care than can be delivered in a general care unit. Progressive care nurses have core competencies that enable them to safely and effectively care for obese patients. A plan of care with interdisciplinary collaboration illustrates the integrative care for obese progressive care patients. (Critical Care Nurse 2016; 36[4]:58-63). PMID:27481802

  20. Bibliotherapy in a Patients' Library *

    PubMed Central

    McDowell, David J.

    1971-01-01

    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

  1. [Falls in patients with dementia].

    PubMed

    Yamaguchi, Kiyoshi

    2008-11-01

    People with cognitive impairment are at about 2 to 3 times higher risk of falling compared with cognitively intact elderly. Incidence of falls among patients with Alzheimer's disease (AD) is high, nevertheless the clinical feature common in patients with mild to moderate AD is the absence of motor impairment. Recent studies suggest that the divided attention markedly impairs the ability of patients with AD to regulate the gait. Falls are particularly common in Dementia with Lewy bodies (DLB) patients and may aid diagnosis, and the falls are associated with parkinsonism and other unclear factors. Treatment studies evaluating fall reduction strategies in dementia patients are a priority. PMID:18974447

  2. Patient-centered medicine and patient-oriented research: improving health outcomes for individual patients

    PubMed Central

    2013-01-01

    Background Patient-centered medicine is developing alongside the concepts of personalized medicine and tailored therapeutics. The main objective of patient-centered medicine is to improve health outcomes of individual patients in everyday clinical practice, taking into account the patient’s objectives, preferences, values as well as the available economic resources. Discussion Patient-centered medicine implies a paradigm shift in the relationship between doctors and patients, but also requires the development of patient-oriented research. Patient-oriented research should not be based on the evaluation of medical interventions in the average patient, but on the identification of the best intervention for every individual patient, the study of heterogeneity and the assignment of greater value to observations and exceptions. The development of information-based technologies can help to close the gap between clinical research and clinical practice, a fundamental step for any advance in this field. Summary Evidence-based medicine and patient centered medicine are not contradictory but complementary movements. It is not possible to practice patient-centered medicine that is not based on evidence, nor is it possible to practice evidence-based medicine at a distance from the individual patient. PMID:23294526

  3. Patient Perspectives on Biosimilar Insulin.

    PubMed

    Wilkins, Alasdair R; Venkat, Manu V; Brown, Adam S; Dong, Jessica P; Ran, Nina A; Hirsch, James S; Close, Kelly L

    2014-01-01

    Given that a new wave of biosimilar insulins will likely enter the market in coming years, it is important to understand patient perspectives on these biosimilars. A survey (N = 3214) conducted by the market research company dQ&A, which maintains a 10 000-patient panel of people with type 1 or type 2 diabetes in roughly equal measure, investigated these perspectives. The survey asked whether patients would switch to a hypothetical less expensive biosimilar insulin that was approved by their provider. Approximately 66% of respondents reported that they would "definitely" or "likely" use a biosimilar insulin, while 17% reported that they were "unlikely" to use or would "definitely not use" such a product. Type 2 diabetes patients demonstrated slightly more willingness to use biosimilars than type 1 diabetes patients. Common patient concerns included whether biosimilars would be as effective as reference products (~650 respondents), whether side effect profiles would deviate from those of reference products (~220 respondents), and the design of the delivery device (~50 respondents). While cost savings associated with biosimilar insulins could increase patient uptake, especially among patients without health insurance (some recent estimates suggest that biosimilars will come at a substantial discount), patients may still need assurance that a cheaper price tag is not necessarily associated with substandard quality. Overall, the dQ&A survey indicates that the majority of patients are willing to consider biosimilar insulins, but manufacturers will need to work proactively to address and assuage patient concerns regarding efficacy, safety, drug administration, and other factors. PMID:24876533

  4. The patient-centered movement.

    PubMed

    Capko, Judy

    2014-01-01

    Patient-centered care has been embraced by government, healthcare leaders, and major insurance plans. This movement began more than 10 years ago, but has expanded considerably in an effort to improve patient outcomes and control healthcare expenses. It is the focus of new payment models that pay physicians and hospitals based on clinical outcomes and patient satisfaction. Efforts contributing to this movement place great importance on the patient visit and interaction with the provider and staff. This includes how well they communicate with and engage patients, the choices they give patients, whether they involve patients in decision-making, and how they build a strong clinical partnership between physician and patients. Recognition programs have been created to give physicians the tools needed to accomplish this goal, including The Patient-Centered Medical Home and the Patient-Centered Specialty Practice. The anticipated gain is population health management and reduced capital expense for medical services. The patient-centered movement has gained momentum, will be watched closely, and is expected to revolutionize the healthcare delivery system in America. PMID:24696963

  5. Patient preparation and scanning techniques.

    PubMed

    Taylor, Carolyn M; Blum, Andrew; Abbara, Suhny

    2010-07-01

    Cardiac computed tomographic angiography (CCTA) is a unique diagnostic modality that can provide a comprehensive assessment of cardiac anatomy. Rapid advances in scanner and software technology have resulted in the ability to noninvasively image the coronary arteries. However, careful patient preparation and scanning technique is required to ensure optimal image quality while minimizing radiation dose delivered. Important components of patient preparation include knowledge of the indications and contraindications for CCTA, patient screening, patient premedication, patient positioning, prescan instruction, and electrocardiograph lead placement. Scanning technique should be determined on a patient by patient basis and tailored according to age and radiation risk, body mass index and chest circumference, heart rate and variability, presence of stents, and coronary calcification. PMID:20705165

  6. [Treatment of patients with osteoarthritis].

    PubMed

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

    2014-01-01

    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

  7. Thrombosis in Lymphoma Patients and in Myeloma Patients.

    PubMed

    Yokoyama, Kenji

    2015-01-01

    The risk of venous thromboembolism (VTE) in patients with cancer is several-fold higher than that in individuals without cancer. Recent studies demonstrated a high incidence of VTE in patients with hematologic malignancies as well as in patients with solid cancers. The reported incidence of VTE in lymphoma is variable, ranging from less than 5% to 59.5%. The incidence of VTE is higher in non-Hodgkin lymphoma than it is in Hodgkin lymphoma. The incidence of VTE also varies according to the disease grade, the disease stage, the performance status of the patient, and the site of disease. Most VTE cases occur at the diagnosis of cancer or early in the course of cancer treatment. An elevated incidence of VTE is also reported in cases of myeloma. VTE occurs in approximately 5% of myeloma patients treated with conventional chemotherapy, and treatment of myeloma patients with immunomodulatory drugs (IMid)-based therapy increases the risk of VTE. Prophylactic aspirin or anticoagulant is used in myeloma patients treated with IMid-based therapy. Several reports have indicated that the incidence of VTE is relatively low in Asian patients treated with IMid-based therapy, and concomitant use of bortezomib reduces the risk of VTE. The incidence of arterial thrombosis is also increased in patients with myeloma and monoclonal gammopathy of undetermined significance. Further studies are needed to develop a predictive model for identifying patients with lymphoma and myeloma who are at high risk for developing thrombosis. PMID:26212069

  8. Thromboprophylaxis with dalteparin in medical patients: which patients benefit?

    PubMed

    Cohen, Alexander T; Turpie, Alexander G G; Leizorovicz, Alain; Olsson, Carl-Gustav; Vaitkus, Paul T; Goldhaber, Samuel Z

    2007-05-01

    It is unclear whether thromboprophylaxis produces a consistent risk reduction in different subgroups of medical patients at risk from venous thromboembolism. We performed a retrospective, post hoc analysis of 3706 patients enrolled in the PREVENT study. Patients were at least 40 years old with an acute medical condition requiring hospitalization for at least 4 days and had no more than 3 days of immobilization prior to enrolment. Patients received either subcutaneous dalteparin (5000 IU) or placebo once daily. The primary end point was the composite of symptomatic deep vein thrombosis (DVT), pulmonary embolism, asymptomatic proximal DVT, or sudden death. Primary diagnosis subgroups were acute congestive heart failure, acute respiratory failure, infectious disease, rheumatological disorders, or inflammatory bowel disease. All patients, except those with congestive heart or respiratory failure, had at least one additional risk factor for venous thromboembolism. A risk reduction was shown in patients receiving dalteparin versus placebo. The relative risk (RR) was 0.73 in patients with congestive heart failure, 0.72 for respiratory failure, 0.46 for infectious disease, and 0.97 for rheumatological disorders. The RR was 0.52 in patients aged > or = 75 years, 0.64 in obese patients, 0.34 for patients with varicose veins, and 0.71 in patients with chronic heart failure. No subgroup had a significantly different response from any other. Importantly, multivariate analysis showed that all patient groups benefited from thromboprophylaxis with dalteparin. Our findings, therefore, support the broad application of thromboprophylaxis in acutely ill hospitalized medical patients. PMID:17615800

  9. Genital reconstruction in exstrophy patients

    PubMed Central

    Nerli, R. B.; Shirol, S. S.; Guntaka, Ajay; Patil, Shivagouda; Hiremath, Murigendra B.

    2012-01-01

    Introduction: Surgery for bladder exstrophy has been evolving over the last four to five decades. Because survival has become almost universal, the focus has changed in the exstrophy-epispadias complex to improving quality of life. The most prevalent problem in the long-term function of exstrophy patients is the sexual activity of the adolescent and adult males. The penis in exstrophy patients appears short because of marked congenital deficiency of anterior corporal tissue. Many patients approach for genital reconstruction to improve cosmesis as well as to correct chordee. We report our series of male patients seeking genital reconstruction following exstrophy repair in the past. Materials and Methods: Fourteen adolescent/adult male patients attended urology services during the period January 2000-December 2009 seeking genital reconstruction following exstrophy repair in the past. Results: Three patients underwent epispadias repair, four patients had chordee correction with cosmetic excision of skin tags and seven patients underwent chordee correction with penile lengthening. All patients reported satisfaction in the answered questionnaire. Patients undergoing penile lengthening by partial corporal dissection achieved a mean increase in length of 1.614 ± 0.279 cm dorsally and 1.543 ± 0.230 cm ventrally. The satisfactory rate assessed by the Short Form-36 (SF-36) showed that irrespective of the different genital reconstructive procedures done, the patients were satisfied with cosmetic and functional outcome. Conclusions: Surgical procedures have transformed the management in these patients with bladder exstrophy. Bladders can be safely placed within the pelvis, with most patients achieving urinary continence and cosmetically acceptable external genitalia. Genital reconstruction in the form of correction of chordee, excision of ugly skin tags and lengthening of penis can be performed to give the patients a satisfactory cosmetic and functional system. PMID:23204655

  10. Simulation: improving patient outcomes.

    PubMed

    Smith, Abi; Siassakos, Dimitrios; Crofts, Joanna; Draycott, Tim

    2013-06-01

    Effective training has been shown to improve perinatal care and outcome, decrease litigation claims and reduce midwifery sick leave. To be effective, training should be incentivised, in a realistic context, and delivered to inter-professional teams similar to those delivering actual care. Teamwork training is a useful addition, but it should be based on the characteristics of effective teamwork as derived from the study of frontline teams. Implementation of simulation and teamwork training is challenging, with constraints on staff time, facilities and finances. Local adoption and adaptation of effective programmes can help keep costs down, and make them locally relevant whilst maintaining effectiveness. Training programmes need to evolve continually in line with new evidence. To do this, it is vital to monitor outcomes and robustly evaluate programmes for their impact on patient care and outcome, not just on participants. PMID:23721770

  11. [Management of splenectomized patients].

    PubMed

    Chambon, J P; Vallet, B; Caiazzo, R; Zerbib, P

    2003-09-01

    PARTIAL SPLENECTOMY: Partial resection is possible in certain indications for splenectomy. Partial splenectomy is the best way to prevent postsplenectomy infections, even though vaccination and antibiotic prophylaxis must be prescribed. This association is also necessary when the patient undergoes an autograft to reimplant splenic tissue or develops splenosis, i.e. fortuitous autotransplantation of splenic parenchyma. GUIDELINES FOR PLANNED SPLENECTOMY: Prophylactic vaccination should be performed 15 days, or 6 weeks, before surgery. Antibiotic prophylaxis includes a preoperative injection of cefazolin followed by intravenous amoxicillin, then Oracilline (Penicilline V) with resumption of oral intake. SURGICAL ASPECTS: Indications for laparoscopic surgery have broadened, laparotomy being reserved for the most difficult cases. Special care is recommended concerning complications, particularly respiratory disorders (pleural effusion, atelectasia) and acute pancreatitis. PMID:14631642

  12. [Nutrition for diabetic patients].

    PubMed

    Schindler, Karin; Brix, Johanna; Dämon, Sabine; Hoppichler, Friedrich; Kruschitz, Renate; Toplak, Hermann; Ludvik, Bernhard

    2016-04-01

    Evidence demonstrates that medical diabetes treatment has to be accompanied by lifestyle modifications. Structured nutrition interventions and increased physical activity will help patients to normalise, respectively maintain their body weight. The main target of a diabetes therapy is aimed at achieving normal or nearly normal blood glucose levels. Reaching this goal may be facilitated by the following nutritional patterns: Using mainly carbohydrates from vegetables, whole grains, legumes and fruits, Restriction of mono- and disaccharides are often important factors in normalising body weight and blood glucose, Reduction of dietary fat could be indicated. However, the primary goal is the limitation of saturated fatty acids which to high percentage are consumed with animal products. There is not sufficient evidence to recommend a dietary protein consumption of more than 20% of energy intake. Individuals with diabetes should be aware of the importance of acquiring daily vitamin and mineral requirements. Natural food sources should be preferred. PMID:27052240

  13. [Neurological presentations of lysosomal diseases in adult patients].

    PubMed

    Sedel, F; Turpin, J-C; Baumann, N

    2007-10-01

    Lysosomal diseases represent a large group of genetic storage disorders characterized by a defect in the catabolism of complex molecules within the lysosome. Effective treatments are now possible for some of them given progresses in bone-marrow transplantation, enzyme replacement therapy and substrate reduction therapy. Neurologists and psychiatrists are concerned by these diseases because they can present in adolescence or adulthood with progressive neuropsychiatric signs. Here we focus on late-onset clinical forms which can be met in an adult neurology or psychiatric department. Lysosomal diseases were classified into 3 groups: (1) leukodystrophies (metachromatic leukodystrophy, Krabbe's disease and Salla's disease); (2) Neurodegenerative or psychiatric-like diseases (GM1 and GM2 gangliosidoses, Niemann Pick type C disease, sialidosis type I, ceroid-lipofuscinosis, mucopolysaccharidosis type III); (3) multisystemic diseases (Gaucher's disease, Fabry's disease, alpha and B mannosidosis, Niemann Pick disease type B, fucosidosis, Schindler/Kanzaki disease, and mucopolysaccharidosis type I and II. We propose a diagnostic approach guided by clinical examination, brain MRI, electrodiagnostic studies and abdominal echography. PMID:18033028

  14. Prescription Opioid Analgesics: Promoting Patient Safety with Better Patient Education.

    PubMed

    Costello, Margaret

    2015-11-01

    Patients expect and deserve adequate postoperative pain relief. Opioid analgesics are widely used and effective in controlling postoperative pain, but their use poses risks that many patients don't understand and that all too often result in adverse outcomes. Inappropriate and often dangerous use of prescription medication has increased sharply in the past two decades in the United States. Patients and caregivers must have an adequate understanding of safe use, storage, and disposal of opioids to prevent adverse drug events in patients and others. Nurses play a key role in providing this patient education. This article provides a case study that highlights the risks and important aspects of opioid medication use in the postoperative patient. PMID:26510070

  15. [Vascular access in diabetic patients. Are these patients "difficult"?].

    PubMed

    Gołębiowski, Tomasz; Weyde, Wacław; Kusztal, Mariusz; Porażko, Tomasz; Augustyniak-Bartosik, Hanna; Madziarska, Katarzyna; Krajewska, Magdalena; Koniński, Przemysław; Sydor, Antoni; Letachowicz, Krzysztof; Klinger, Marian

    2015-01-01

    Diabetics with stage V chronic kidney disease (CKD) on hemodialysis (HD) are considered as "difficult patients", because of problems with creation of the vascular access. There is controversy regarding the results and recommendations for preparation of the vascular access in these patients. The aim of this retrospective study was to evaluate the results of creating different types of arteriovenous fistula (AVFs) in consecutive series of patients starting dialysis treatment. The analysis was performed in 741 patients (385 females and 356 males), average age 61.4±7 years, who started dialysis treatment in our department between January 2005 and December 2012. Native AVFs were created in all patients. No patients received an AVF requiring synthetic graft material. The number of patients with diabetic nephropathy was 166 (22.4%). Among them, 30 (18%) had type 1 diabetes and 136 (82%) type 2. In this group the occurrence of calcification in the forearm artery was estimated on the basis of physical examination, Allan's test, Doppler ultrasound and forearm X-ray. In a subgroup of patients with atherosclerotic changes in the arterial system the frequency of failed AVFs was analyzed. These results were compared with the group without diabetes. The number of procedures necessary for successfu AVF creation and type of access was counted in both groups. The assessment of the procedure frequency and AVF location in diabetic and in non-diabetic patients was made by χ² test with Yates correction. In the group of 166 patients with diabetes, in 100 cases (60%) atherosclerotic changes in forearm arteries were observed. In a subgroup of 30 patients with type 1 diabetes atherosclerosis was observed in 17 adults (57%). In this subgroup creation of a suitable forearm AVF in the first procedure in 9 patients was possible and in the other 8 cases the atherosclerotic changes necessitated repeated procedures and were an important obstacle to create the AVF. In the subgroup of 136

  16. Complement activity is associated with disease severity in multifocal motor neuropathy

    PubMed Central

    Vlam, Lotte; Cats, Elisabeth A.; Harschnitz, Oliver; Jansen, Marc D.; Piepers, Sanne; Veldink, Jan Herman; Franssen, Hessel; Stork, Abraham C.J.; Heezius, Erik; Rooijakkers, Suzan H.M.; Herpers, Bjorn L.; van Strijp, Jos A.; van den Berg, Leonard H.

    2015-01-01

    Objective: To investigate whether high innate activity of the classical and lectin pathways of complement is associated with multifocal motor neuropathy (MMN) and whether levels of innate complement activity or the potential of anti-GM1 antibodies to activate the complement system correlate with disease severity. Methods: We performed a case-control study including 79 patients with MMN and 79 matched healthy controls. Muscle weakness was documented with Medical Research Council scale sum score and axonal loss with nerve conduction studies. Activity of the classical and lectin pathways of complement was assessed by ELISA. We also determined serum mannose-binding lectin (MBL) concentrations and polymorphisms in the MBL gene (MBL2) and quantified complement-activating properties of anti-GM1 IgM antibodies by ELISA. Results: Activity of the classical and lectin pathways, MBL2 genotypes, and serum MBL concentrations did not differ between patients and controls. Complement activation by anti-GM1 IgM antibodies was exclusively mediated through the classical pathway and correlated with antibody titers (p < 0.001). Logistic regression analysis showed that both high innate activity of the classical pathway of complement and high complement-activating capacity of anti-GM1 IgM antibodies were significantly associated with more severe muscle weakness and axonal loss. Conclusion: High innate activity of the classical pathway of complement and efficient complement-activating properties of anti-GM1 IgM antibodies are determinants of disease severity in patients with MMN. These findings underline the importance of anti-GM1 antibody–mediated complement activation in the pathogenesis and clinical course of MMN. PMID:26161430

  17. Lipoplasty in the bulimic patient.

    PubMed

    Willard, S G; McDermott, B E; Woodhouse, L M

    1996-08-01

    Recent cases in our Eating Disorders Clinic suggest that patients diagnosed with bulimia nervosa seeking surgical fat removal may be exhibiting a variant of the purging behavior seen in bulimic patients. These same patients exhibit historical or concurrent abuse of laxatives and/or diuretics or self-induced vomiting in a pathologic attempt to obtain or maintain an idealized body image. This paper presents two case studies that illustrate the bulimic patient's compulsive quest for lipectomy with unrealistic expectations that surgical alteration of the body will be an emotional and physical panacea. Plastic surgeons must be cautioned regarding this potential manifestation of bulimia nervosa and the dangers inherent in colluding with the patient in a pathologic request for surgery. It is important for plastic surgeons to recognize appropriate use of lipectomy as an alternative to traditional purging behavior in the bulimic patient. PMID:8764715

  18. Thyroid Disease in the Older Patient

    MedlinePlus

    ... these patients, without treatment unless they are symptomatic. HYPOTHYROIDISM IN THE OLDER PATIENT Hypothyroidism is very common ... is given. TREATMENT OF THE OLDER PATIENT WITH HYPOTHYROIDISM As with the younger patient, pure synthetic thyroxine ( ...

  19. Implementing national patient safety alerts.

    PubMed

    Moore, Sally; Taylor, Natalie; Lawton, Rebecca; Slater, Beverley

    National patient safety alerts are sometimes difficult to implement in an effective way. All trusts have to declare compliance with alerts as part of a three-step process to improve patient safety. This article discusses an alternative way of implementing national patient safety alerts and describes how behaviour-change methods can be used to successfully implement lasting changes in practice at ward or departmental level. PMID:27145671

  20. Thromboprophylaxis in immobilized medical patients.

    PubMed

    Vaitkus, Paul T

    2004-03-30

    Venous thromboembolism accounts for a large number of preventable deaths. The majority of these events occur in medical patients, but medical thromboprophylaxis remains underutilised in this population. The purpose of this review is to examine the results of recent clinical trials of low molecular weight heparins in the prevention of venous thromboembolic disease in medical patients. The available data make a compelling case in favor of widespread use of low molecular weight heparin in medical patients. PMID:15096323

  1. [Sophrology for patients in oncology].

    PubMed

    Barré, Chantal; Falcou, Marie-Christine; Mosseri, Véronique; Carrié, Sylvie; Dolbeault, Sylvie

    2015-11-01

    It is important to support patients with cancer during their care pathway and even beyond. They undergo long and difficult treatments, all anxiety-causing situations and sources of stress. Sophrological techniques help patients to find calm, lessen their fears and offer them the opportunity to work on themselves through simple easily reproducible exercises. This observation has been verified by a study carried out at the Institut Curie with patients undergoing chemotherapy. PMID:26567064

  2. [Feasibility of tailored patient education].

    PubMed

    Tóth, Tamás; Dinya, Elek

    2013-03-17

    Patient education has an important role in the prevention and therapy. It enables the delivery of necessary information, development of skills and motivations and supporting to cope with the disease. Although many information sources are available, it is still necessary to provide organized patient education. Tailored patient education was proved to be more effective than using general information materials. The proper use of information technology enables the widespread and cost-effective implementation of tailored patient education. The authors analyse the components necessary for development of such a system. PMID:23477894

  3. Effective writing that attracts patients.

    PubMed

    Baum, Neil

    2015-01-01

    Doctors today not only must communicate verbally, they must also realize that the written word is important to their ability to connect with the patients that they already have and also to attract new patients. Doctors will be expected to write blogs, to create content for their Web sites, to write articles for local publications, and even to learn to express themselves in 140 characters or less (i.e., Twitter). This article presents 10 rules for selecting the right words to enhance your communication with existing patients and potentially to attract new patients to your practice. PMID:26062324

  4. Bed bathing patients in hospital.

    PubMed

    Downey, Lindsey; Lloyd, Hilary

    There are a number of circumstances that may affect an individual's ability to maintain personal hygiene. Hospitalised patients, and in particular those who are bedridden, may become dependent on nursing staff to carry out their hygiene needs. Assisting patients to maintain personal hygiene is a fundamental aspect of nursing care. However, it is a task often delegated to junior or newly qualified staff. This article focuses on the principles of bed bathing patients in hospital, correct procedure and the importance of maintaining patient dignity and respect in clinical practice. PMID:18543852

  5. Defining and Measuring Patient Satisfaction.

    PubMed

    Graham, Brent

    2016-09-01

    Reporting patient satisfaction has become an increasingly common component of studies evaluating treatment outcomes. However the construct of "patient satisfaction" is one that is complex and context dependent. While there is no question that careful, reliable, and valid measurement of this important aspect of patient care is required, tools for achieving this objective have not been fully developed. Measures of patient satisfaction that reflect the unique role of the hand in everyday life will require the same approach to instrument development as has been used to move forward the field of outcome measurement in general. PMID:27570227

  6. Patient involvement in patient safety: Protocol for developing an intervention using patient reports of organisational safety and patient incident reporting

    PubMed Central

    2011-01-01

    Background Patients have the potential to provide a rich source of information on both organisational aspects of safety and patient safety incidents. This project aims to develop two patient safety interventions to promote organisational learning about safety - a patient measure of organisational safety (PMOS), and a patient incident reporting tool (PIRT) - to help the NHS prevent patient safety incidents by learning more about when and why they occur. Methods To develop the PMOS 1) literature will be reviewed to identify similar measures and key contributory factors to error; 2) four patient focus groups will ascertain practicality and feasibility; 3) 25 patient interviews will elicit approximately 60 items across 10 domains; 4) 10 patient and clinician interviews will test acceptability and understanding. Qualitative data will be analysed using thematic content analysis. To develop the PIRT 1) individual and then combined patient and clinician focus groups will provide guidance for the development of three potential reporting tools; 2) nine wards across three hospital directorates will pilot each of the tools for three months. The best performing tool will be identified from the frequency, volume and quality of reports. The validity of both measures will be tested. 300 patients will be asked to complete the PMOS and PIRT during their stay in hospital. A sub-sample (N = 50) will complete the PMOS again one week later. Health professionals in participating wards will also be asked to complete the AHRQ safety culture questionnaire. Case notes for all patients will be reviewed. The psychometric properties of the PMOS will be assessed and a final valid and reliable version developed. Concurrent validity for the PIRT will be assessed by comparing reported incidents with those identified from case note review and the existing staff reporting scheme. In a subsequent study these tools will be used to provide information to wards/units about their priorities for patient

  7. Patient Education Leads to Better Care for Heart Patients.

    ERIC Educational Resources Information Center

    Rosenberg, Stanley G.

    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…

  8. Patient or customer?

    PubMed

    Parker, J M

    1999-01-01

    This paper investigates caring in practice within the context of the global imperative of increasing rationalisation of care based on an economic ethic. The notion of the global marketplace has spread to the domain of health services, so that 'health' has come to be seen as a commodity, with the body as its site, and the 'patient' a customer; clinicians work to construct standard pathways through the healthcare supermarket. The challenge for nurses is to work within but also to challenge and resist the reductionist impetus of economically based and commercially driven approaches to health care. They must retain the sense of the value of the wholeness of the person, the deeply personal and profoundly significant professional-recipient relationship, and find ways of demonstrating their capacity to deliver high-quality care in a cost-effective way. Proper and appropriate accountability is a key strategy to maintaining quality nursing as a significant aspect of care. The expansion of the role of the advanced practice nurse is very useful in providing holistic and cost-effective care, though there are currently limitations to scope of practice that need to be removed. The metaphor of the marketplace, underpinned by powerful global economic forces, can draw us into unthinking compliance with its imperatives--but other metaphors are available. Metaphor and creativity are linked, and we need to consider how the creative use of language can facilitate the emergence of new ways of understanding in health care. PMID:10401282

  9. What Do Patients Want? Patient Preference in Wound Care

    PubMed Central

    Corbett, Lisa Q.; Ennis, William J.

    2014-01-01

    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

  10. Adequacy of dialysis: the patient's role and patient concerns.

    PubMed

    Newmann, John M; Litchfield, William E

    2005-03-01

    The patient's role in adequacy of hemodialysis is demanding and complex. It requires meticulous attention to initiating, accepting, and maintaining extraordinary behavioral change. This includes the following: (1) major alteration of dietary habits, often contrary to a patient's familial and cultural customs; (2) compliance with a new, voluminous medication routine, often straining personal finances; (3) reallocation of time for transportation, treatment, and partial recovery, frequently consuming a minimum of 6 to 8 hours 3 days each week; (4) psychologic adjustment to unaccustomed chronic dependency on, and accountability to, an array of variably experienced and competent renal care staff; (5) skills, seldom taught, required to communicate clearly and regularly with overworked medical professionals who are often much younger with less life experience; and (6) additional commitment to compensating for the physical fatigue that routinely accompanies hemodialysis. Reasonable behavioral modification in these 6 categories is likely to increase the chances of a patient fulfilling his role in adequacy of dialysis. Some patients, however committed the staff have been in assisting them, may show little interest in dialysis adequacy and the patient's role. Other patients periodically may fail in their role unless the renal care team recognizes the patient as an individual who is included as an important team member. The patient requires consistent and repeated education about their disease, treatment, and risks and benefits of adherence. The unique, unnatural requirements of adequate chronic hemodialysis require this patient support from the renal staff, enhanced by continuous sensitive attention, empathy, and persuasion. This will help the patient achieve success in their role. PMID:15791563

  11. Anaesthetic management of neurosurgical patients.

    PubMed

    Himmelseher, S; Pfenninger, E

    2001-10-01

    Anaesthetic care of neurosurgical patients increasingly involves management issues that apply not only to 'asleep patients', but also to 'awake and waking-up patients' during and after intracranial operations. On one hand, awake brain surgery poses unique anaesthetic challenges for the provision of awake brain mapping, which requires that a part of the procedure is performed under conscious patient sedation. Recent case reports suggest that local infiltration anaesthesia combined with sedative regimens using short-acting drugs and improved monitoring devices have assumed increasing importance. These techniques may optimize rapid adjustments of the narcotic depth, providing analgesia and patient immobility yet permitting a swift return to cooperative patient alertness for functional brain tests. Regional anaesthesia and peripheral nerve blocks were used to prevent uncontrolled movements in special cases of intractable seizures. However, few of these strategies have been evaluated in controlled trials. Awake craniotomy for tumour removal is performed as early discharge surgery. Meticulous consideration of postoperative patient safety is therefore strongly advised. On the other hand, waking-up patients or the emergence from general anaesthesia after brain surgery is still an area with considerable variation in clinical practice. Developments indicate that fast-acting anaesthetic agents and prophylactic strategies to prevent postoperative complications minimize the adverse effects of anaesthesia on the recovery process. Recent data do not advocate a delay in extubating patients when neurological impairment is the only reason for prolonged intubation. An appropriate choice of sedatives and analgesics during mechanical ventilation of neurosurgical patients allows for a narrower range of wake-up time, and weaning protocols incorporating respiratory and neurological measures may improve outcome. In conclusion, despite a lack of key evidence to request 'fast

  12. National survey of hospital patients.

    PubMed Central

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

    1994-01-01

    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

  13. Patient Perspectives on Biosimilar Insulin

    PubMed Central

    Wilkins, Alasdair R.; Venkat, Manu V.; Brown, Adam S.; Dong, Jessica P.; Ran, Nina A.; Hirsch, James S.

    2014-01-01

    Given that a new wave of biosimilar insulins will likely enter the market in coming years, it is important to understand patient perspectives on these biosimilars. A survey (N = 3214) conducted by the market research company dQ&A, which maintains a 10 000-patient panel of people with type 1 or type 2 diabetes in roughly equal measure, investigated these perspectives. The survey asked whether patients would switch to a hypothetical less expensive biosimilar insulin that was approved by their provider. Approximately 66% of respondents reported that they would “definitely” or “likely” use a biosimilar insulin, while 17% reported that they were “unlikely” to use or would “definitely not use” such a product. Type 2 diabetes patients demonstrated slightly more willingness to use biosimilars than type 1 diabetes patients. Common patient concerns included whether biosimilars would be as effective as reference products (~650 respondents), whether side effect profiles would deviate from those of reference products (~220 respondents), and the design of the delivery device (~50 respondents). While cost savings associated with biosimilar insulins could increase patient uptake, especially among patients without health insurance (some recent estimates suggest that biosimilars will come at a substantial discount), patients may still need assurance that a cheaper price tag is not necessarily associated with substandard quality. Overall, the dQ&A survey indicates that the majority of patients are willing to consider biosimilar insulins, but manufacturers will need to work proactively to address and assuage patient concerns regarding efficacy, safety, drug administration, and other factors. PMID:24876533

  14. Blood transfusion: patient identification and empowerment.

    PubMed

    Stout, Lynn; Joseph, Sundari

    Positive patient identification is pivotal to several steps of the transfusion process; it is integral to ensuring that the correct blood is given to the correct patient. If patient misidentification occurs, this has potentially fatal consequences for patients. Historically patient involvement in healthcare has focused on clinical decision making, where the patient, having been provided with medical information, is encouraged to become involved in the decisions related to their individualised treatment. This article explores the aspects of patient contribution to patient safety relating to positive patient identification in transfusion. When involving patients in their care, however, clinicians must recognise the diversity of patients and the capacity of the patient to be involved. It must not be assumed that all patients will be willing or indeed able to participate. Additionally, clinicians' attitudes to patient involvement in patient safety can determine whether cultural change is successful. PMID:26878405

  15. Patient preference: a comparison of electronic patient-completed questionnaires with paper among cancer patients.

    PubMed

    Martin, P; Brown, M C; Espin-Garcia, O; Cuffe, S; Pringle, D; Mahler, M; Villeneuve, J; Niu, C; Charow, R; Lam, C; Shani, R M; Hon, H; Otsuka, M; Xu, W; Alibhai, S; Jenkinson, J; Liu, G

    2016-03-01

    In this study, we compared cancer patients preference for computerised (tablet/web-based) surveys versus paper. We also assessed whether the understanding of a cancer-related topic, pharmacogenomics is affected by the survey format, and examined differences in demographic and medical characteristics which may affect patient preference and understanding. Three hundred and four cancer patients completed a tablet-administered survey and another 153 patients completed a paper-based survey. Patients who participated in the tablet survey were questioned regarding their preference for survey format administration (paper, tablet and web-based). Understanding was assessed with a 'direct' method, by asking patients to assess their understanding of genetic testing, and with a 'composite' score. Patients preferred administration with tablet (71%) compared with web-based (12%) and paper (17%). Patients <65 years old, non-Caucasians and white-collar professionals significantly preferred the computerised format following multivariate analysis. There was no significant difference in understanding between the paper and tablet survey with direct questioning or composite score. Age (<65 years) and white-collar professionals were associated with increased understanding (both P = 0.03). There was no significant difference in understanding between the tablet and print survey in a multivariate analysis. Patients overwhelmingly preferred computerised surveys and understanding of pharmacogenomics was not affected by survey format. PMID:25899560

  16. Idiom Comprehension in Aphasic Patients

    ERIC Educational Resources Information Center

    Papagno, Costanza; Tabossi, Patrizia; Colombo, Maria Rosa; Zampetti, Patrizia

    2004-01-01

    Idiom comprehension was assessed in 10 aphasic patients with semantic deficits by means of a string-to-picture matching task. Patients were also submitted to an oral explanation of the same idioms, and to a word comprehension task. The stimuli of this last task were the words following the verb in the idioms. Idiom comprehension was severely…

  17. Pharmacotherapeutics for the AIDS Patient.

    ERIC Educational Resources Information Center

    Fife, Kenneth H.

    1991-01-01

    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…

  18. Art Therapy with Laryngectomy Patients.

    ERIC Educational Resources Information Center

    Anand, Susan Ainlay; Anand, Vinod K.

    1997-01-01

    Reports on the experiences of patients with laryngeal cancer who used art therapy. Drawing on 14 years of experience and 109 laryngeal cancer patients, describes treatment results and the case material substantiating the distinct role of art therapy. Provides an overview of the special medical and therapeutic needs of this group. (RJM)

  19. The Coronary Patient in Industry

    NASA Technical Reports Server (NTRS)

    Schuster, B.

    1971-01-01

    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.

  20. Optimizing patient-ventilator synchrony.

    PubMed

    Epstein, S K

    2001-01-01

    Mechanical ventilation assumes the work of breathing, improves gas exchange, and unloads the respiratory muscles, all of which require good synchronization between the patient and the ventilator. Causes for patient-ventilator dyssynchrony include both patient factors (abnormalities of respiratory drive and abnormal respiratory mechanics) and ventilator factors (triggering, flow delivery, breath termination criteria, the level and mode of ventilator support, and imposed work of breathing). Although patient-ventilator dyssynchrony can often be detected on physical exam, careful analysis of ventilator waveforms (pressure-time, flow-time) allows for more precise definition of the underlying cause. Patient-ventilator interaction can be improved by reversing patient factors that alter respiratory drive or elevate patient ventilatory requirements and by correcting factors that contribute to dynamic hyperinflation. Proper setting of the ventilator using sensitive triggering mechanisms, satisfactory flow rates, adequate delivered minute ventilation, matching machine T(I) to neural T(I), and applying modes that overcome the imposed work of breathing, further optimize patient-ventilator synchrony. PMID:16088669

  1. Mycobacterium arupense in Cancer Patients

    PubMed Central

    Al Hamal, Zainab; Jordan, Mary; Hachem, Ray Y.; Alawami, Hussain M.; Alburki, Abdussalam M.; Yousif, Ammar; Deshmukh, Poonam; Jiang, Ying; Chaftari, Ann-Marie; Raad, Issam I.

    2016-01-01

    Abstract Mycobacterium arupense is a slow-growing, nonchromogenic, acid-fast bacillus. Its clinical spectrum, epidemiology, and frequency of colonization versus true infection remain unknown. We evaluated the clinical significance of M arupense and positive cultures from cancer patients. We retrospectively reviewed records of all cancer patients treated at our institution between 2007 and 2014 to identify those who had positive cultures for M arupense. Mycobacterium arupense was identified by sequencing the 16S rRNA and hsp65 genes. A total of 53patients had positive cultures, 100% of which were isolated from respiratory specimens. Of these, 7 patients met the American Thoracic Society/Infectious Diseases Society of America criteria for a definitive diagnosis of M arupense infection, 14 cases were considered to be probable infections, and 29 cases were considered to be possible infections. Of the included patients, 13 received therapy for M arupense infection and 40 did not. The outcomes of treated and untreated patients did not differ significantly. No relapses of M arupense infection. In addition, there were no M arupense-related deaths in either group. In cancer patients, M arupense appears to be mostly a commensal organism rather than a pathogen. Patients who did or did not receive treatment had similar outcomes. Validation of these findings in a larger prospective trial is warranted. PMID:27057825

  2. Viscoelastic cushion for patient support

    NASA Technical Reports Server (NTRS)

    Sauers, D. G.

    1971-01-01

    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.

  3. Patient's breath controls comfort devices

    NASA Technical Reports Server (NTRS)

    Schrader, M.; Carpenter, B.; Nichols, C. D.

    1972-01-01

    Patient assist system for totally disabled persons was developed which permits a person, so paralyzed as to be unable to move, to activate by breathing, a call system to summon assistance, turn the page of a book, ajust his bed, or do any one of a number of other things. System consists of patient assist control and breath actuated switch.

  4. Virtual Patients in Geriatric Education

    ERIC Educational Resources Information Center

    Tan, Zaldy S.; Mulhausen, Paul L.; Smith, Stephen R.; Ruiz, Jorge G.

    2010-01-01

    The virtual patient is a case-based computer program that combines textual information with multimedia elements such as audio, graphics, and animation. It is increasingly being utilized as a teaching modality by medical educators in various fields of instruction. The inherent complexity of older patients and the shortage of geriatrics educators…

  5. Patient Disclosure of Medical Misdeeds

    ERIC Educational Resources Information Center

    Bergen, Clara; Stivers, Tanya

    2013-01-01

    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…

  6. Patient Relations and Workplace Communication.

    ERIC Educational Resources Information Center

    Career Resources Development Center, Inc., San Francisco, CA.

    The workbook contains lessons and exercises in patient relations and workplace communication in a medical services office, particularly for interactions involving one or more non-native speaker of English. Seven units address these topics: (1) greetings and basic assistance, greeting established patients, and measuring height and weight and taking…

  7. Coping strategies in melanoma patients.

    PubMed

    Trapp, Michael; Trapp, Eva-Maria; Richtig, Erika; Egger, Josef Wilhelm; Zampetti, Anna; Sampogna, Francesca; Rohrer, Peter Michael; Komericki, Peter; Strimitzer, Tanja; Linder, Michael Dennis

    2012-11-01

    An observational, questionnaire-based, cross-sectional study was performed to assess whether differences in coping behaviour (positive and negative strategies) between patients with either a recent diagnosis of malignant melanoma (MM) or with benign dermatological disease, were predictive of the diagnosis. Coping strategies were assessed with the German version of the stress-coping questionnaire (SVF 120) in 46 inpatients for whom surgery was planned at the Department of Dermatology, Medical University of Graz, Austria. Subjects were divided into two groups: patients with non-metastatic MM, and patients with benign dermatological diseases (controls). The risk for the diagnosis "melanoma" decreased with higher values of "situation control" (p = 0.007) and increased with higher values of resignation (p = 0.035) and trivialisation (p = 0.039). More-over, the risk for having a MM with thickness > 1 mm decreased in patients with higher values in positive coping strategies (p < 0.34). These results suggest differences in coping behaviour between patients with MM and those with benign skin diseases and, amidst patients with MM, between patients with different MM thickness; the results may hence lead to earlier, more specific and more effective psychological interventions to improve coping in patients with MM, as differences in coping behaviour seem to appear even in the non-metastatic stage of the disease. PMID:22772950

  8. Defining patient-nurse boundaries.

    PubMed

    Barrow, Rebecca; Mee, Steve; Buckley, Alison; Corless, Louise

    This series exploring how narratives can be used to reflect on practice has focused on patient narratives. This sixth article uses nurse narratives to explore professional boundaries between patients and nurses. These can be difficult to negotiate and can depend on individual circumstances: what may be appropriate in one situation may be unacceptable in another. PMID:27295800

  9. Are rhinoplasty patients potentially mad?

    PubMed

    Slator, R; Harris, D L

    1992-01-01

    Rhinoplasty patients have long been considered to be psychologically unstable and therefore a "risky" group upon which to operate. Patients who had rhinoplastic operations more than 5 years ago were contacted by post and their psychological health assessed by the use of psychometric tests. The results show no evidence to support earlier suggestions that requests for rhinoplasty may be early symptoms of severe psychiatric disease. However, several points do emerge. Male patients show more symptoms of anxiety and depression than normal, and female patients who give no history of injury preceding their operation behave in a more extrovert and sociable manner than normal. Furthermore, patients of both sexes who give no history of injury before their operation, even though pleased with the operative results, are more self-conscious of their appearance than those who were injured prior to their rhinoplasty. PMID:1623348

  10. Psychodynamic Psychotherapy for Cancer Patients

    PubMed Central

    Straker, Norman

    1998-01-01

    Psychodynamic psychotherapy is effective as an approach to understanding the psychological conflicts and the psychiatric symptoms of cancer patients as well as to planning useful psychological interventions. The author recommends that the psychotherapist who treats cancer patients be familiar with the following: 1) the natural course and treatment of the illness, 2) a flexible approach in accord with the medical status of the patient, 3) a common sense approach to defenses, 4) a concern with quality-of-life issues, and 5) counter- transference issues as they relate to the treatment of very sick patients. Case reports illustrate the unique problems facing psychotherapists who are treating cancer patients. Further, these cases show the effective use of psychodynamic principles to inform the therapist of successful psychotherapeutic interventions. PMID:9407471

  11. The cost of patient safety.

    PubMed

    Hoeltge, Gerald A

    2004-01-01

    To ensure patient safety, it costs an organization time, money, and commitment. The clinical laboratory may promote patient safety or may contribute to medical error. Laboratory errors put a patient at risk at any point along the path of workflow. The cost of an initiative in patient safety may be considered from four perspectives: compliance, feasibility, present risk, and financial. Three examples are offered to illustrate the use of these approaches. Most patient-safety strategies in laboratory medicine are not expensive. They are affordable with a structured outlay of existing resources and a willingness to follow defined work practices without exception. More extensive projects, especially those that cross jurisdictional lines within an organization, do require comprehensive project management. Management ofboth kinds of initiatives is addressed by NCCLS' documents on quality practice. PMID:15597552

  12. Endodontics and the ageing patient.

    PubMed

    Johnstone, M; Parashos, P

    2015-03-01

    Patients are living longer and the rate of edentulism is decreasing. Endodontic treatment is an essential part of maintaining the health and well-being of the elderly. Retention of natural teeth improves the quality of life and the overall health and longevity of ageing patients. Also, teeth that might be otherwise extracted may be strategically valuable to retain a prosthesis, and elderly patients are more likely to have medical complications that may prevent dental extractions from being safely performed. The technical goals of endodontic treatment in the elderly are the same as those for younger patients. However, the pulpo-dentinal complex undergoes calcific changes over time, which may pose challenges for the clinician. The purposes of this review are to discuss age changes in the pulp and the challenges posed by diagnosing, treatment planning and treating the elderly endodontic patient. PMID:25762039

  13. Mediating consolation with suicidal patients.

    PubMed

    Gilje, Fredricka; Talseth, Anne-Grethe

    2007-07-01

    Psychiatric nurses frequently encounter suicidal patients. Caring for such patients often raises ethical questions and dilemmas. The research question for this study was: 'What understandings are revealed in texts about consolation and psychiatric nurses' responses to suicidal patients?' A Gadamerian approach guided re-interpretation of published texts. Through synthesizing four interpretive phases, a comprehensive interpretation emerged. This revealed being 'at home' with self, or an ethical way of being, as a hermeneutic understanding of a way to become ready to mediate consolation with suicidal patients. Trustworthiness was addressed by means of the qualities of auditability, credibility and confirmability. This re-interpretation adds to nursing knowledge, enhances understanding of previous research findings, provides pre-understanding for further research and reveals the value of hermeneutic inquiry in nursing. It also deepens understanding of a published model of consolation. These understandings may help to guide nurses who are struggling with suicidal patients. PMID:17562733

  14. Iranian patients' perspective of patients' rights: a qualitative study.

    PubMed

    Khaledi, Shahnaz; Moridi, Golrokh; Valiee, Sina

    2016-01-01

    There is an increasing emphasis on "protecting patient rights", which has a great influence on the patient's well-being. This study aimed to explore patients' perspectives of patients' rights in the hospitals of Kurdistan University of Medical Sciences in Iran. This qualitative study used the content analysis method. The data were collected through in-depth interviews, conducted in Persian at the internal and surgical wards from 2012 to 2013. Consequently, interviews continued to be conducted on 20 patients, using content analysis, until data saturation. The findings highlighted aspects of patients' rights and five themes emerged from the interviews: having one's dignity respected, receiving care of the requisite quality, being shown financial consideration, receiving adequate information, and having a desirable and pleasant environment. The patients believed that for their rights to be upheld, it is necessary that together with the provision of enough facilities and equipment, they need to be respected and offered ideal healthcare services. This could be achieved by removing barriers and facilitating procedures. PMID:26826656

  15. 'The patient': at the center of patient-reported outcomes.

    PubMed

    Awad, A George

    2015-01-01

    The recent emphasis of including patient reports in their own care management is reviewed in terms of the factors that contributed to its popularity. The role change of patients as being active participants in their own care as a result of the rising consumerism and advocacy has led to increased pressures for including patients in the therapeutic decision-making process. As consumers of clinical services, their perspectives and attitudes towards health and illness acquired more importance. The rising cost of healthcare has added another dimension in cost containment by empowering patients and sharing responsibility in their recovery, which hopefully can improve outcomes. Challenges in the development and implementation of patient-reported outcomes in psychiatry are reviewed and include the still unresolved subjective/objective dichotomy, identification of the most appropriate and relevant patient-reported outcomes. Few outcomes are identified and include: subjective tolerability of medication, self-reported health-related quality of life, preferences, patients' attitudes towards health and illness, satisfaction with medication and overall satisfaction of quality of care, and functional state, with particular focus on social functioning. PMID:26289737

  16. Patient Admission Preferences and Perceptions

    PubMed Central

    Wu, Clayton; Melnikow, Joy; Dinh, Tu; Holmes, James F.; Gaona, Samuel D.; Bottyan, Thomas; Paterniti, Debora; Nishijima, Daniel K.

    2015-01-01

    Introduction Understanding patient perceptions and preferences of hospital care is important to improve patients’ hospitalization experiences and satisfaction. The objective of this study was to investigate patient preferences and perceptions of hospital care, specifically differences between intensive care unit (ICU) and hospital floor admissions. Methods This was a cross-sectional survey of emergency department (ED) patients who were presented with a hypothetical scenario of a patient with mild traumatic brain injury (TBI). We surveyed their preferences and perceptions of hospital care related to this scenario. A closed-ended questionnaire provided quantitative data on patient preferences and perceptions of hospital care and an open-ended questionnaire evaluated factors that may not have been captured with the closed-ended questionnaire. Results Out of 302 study patients, the ability for family and friends to visit (83%), nurse availability (80%), and physician availability (79%) were the factors most commonly rated “very important,” while the cost of hospitalization (62%) and length of hospitalization (59%) were the factors least commonly rated “very important.” When asked to choose between the ICU and the floor if they were the patient in the scenario, 33 patients (10.9%) choose the ICU, 133 chose the floor (44.0%), and 136 (45.0%) had no preference. Conclusion Based on a hypothetical scenario of mild TBI, the majority of patients preferred admission to the floor or had no preference compared to admission to the ICU. Humanistic factors such as the availability of doctors and nurses and the ability to interact with family appear to have a greater priority than systematic factors of hospitalization, such as length and cost of hospitalization or length of time in the ED waiting for an in-patient bed. PMID:26587095

  17. Preoperative patient assessment: Identifying patients at high risk.

    PubMed

    Boehm, O; Baumgarten, G; Hoeft, A

    2016-06-01

    Postoperative mortality remains alarmingly high with a mortality rate ranging between 0.4% and 4%. A small subgroup of multimorbid and/or elderly patients undergoing different surgical procedures naturally confers the highest risk of complications and perioperative death. Therefore, preoperative assessment should identify these high-risk patients and stratify them to individualized monitoring and treatment throughout all phases of perioperative care. A "tailored" perioperative approach might help further reduce perioperative morbidity and mortality. This article aims to elucidate individual morbidity-specific risks. It further suggests approaches to detect patients at the risk of perioperative complications. PMID:27396802

  18. Confabulations in alcoholic Korsakoff patients.

    PubMed

    Borsutzky, Sabine; Fujiwara, Esther; Brand, Matthias; Markowitsch, Hans J

    2008-11-01

    Besides forgetting, memory is also prone to distortions, errors and illusions. Confabulation is one type of memory distortion that may occur in cases of brain damage. Although confabulations are described anecdotally in patients with alcoholic Korsakoff syndrome (KS), there are few systematic investigations of the presence and nature of these types of false memories in KS. Moreover, it is unclear whether KS patients' confabulations evenly affect all types of memories, or whether certain memory domains are more susceptible. Our study attempted to clarify two questions: first, whether confabulations are a critical feature of the cognitive impairment associated with long-term KS in a large sample of patients (N=42). Second, we investigated which memory domain is most likely affected by confabulations in KS. To elicit confabulations, we used a Confabulation Interview containing questions from different memory domains. We found that KS patients overall confabulated more compared to a group of healthy subjects. Furthermore, we found that patients confabulated most within the episodic/autobiographical memory domain. Our results imply that besides pronounced memory deficits typically associated with KS, confabulation can also be regarded as a clinical feature of the disease. The preponderance of episodic confabulation obtained here by using a standardized test, confirms anecdotic reports that KS patients confabulate in everyday life mainly with respect to their personal past and present. Thus, for a detailed description of the memory profile of KS patients, the screening of confabulation tendencies may be a useful supplementary clinical tool. PMID:18675286

  19. Identity disturbance in distant patients.

    PubMed

    Hoffman, Irwin

    2013-04-01

    Chronically distant, emotionally isolated patients often present with identity disturbance. Identity, it is argued, develops as a thematic pattern of narcissism, shaped by the nature of the mother's early libidinal influences on the child's sense of self. Identity provides a form of self-definition that addresses the question, Who am I? In the treatment of these patients, resistances to narcissistic vulnerabilities (narcissistic resistances) provide an illusory sense of security and induce the analyst to avoid attention to a central pathological problem: primitive and frightening needs for, and unconscious fantasies of, dependence on, and functionality for, another. Patients' avoidance of material and therapeutic interactions that deal with their dependencies are aspects of a tacit contract with the analyst to foreclose examination of their considerable problems with inner stability. Among these problems are anxieties regarding intrusion and loss of separateness. As analysis proceeds, elements of such a patient's identity become clarified and are used to understand and organize the material for both analyst and patient. This can allow the patient to articulate a more embodied and vital experience of individuality. A case is presented to illustrate the analysis of a patient using this approach. PMID:23526544

  20. [Adrenal insufficiency in cirrhotic patients].

    PubMed

    Orozco, Federico; Anders, María; Mella, José; Antinucci, Florencia; Pagano, Patricia; Esteban, Paula; Cartier, Mariano; Romero, Gustavo; Francini, Bettina; Mastai, Ricardo

    2016-01-01

    Relative adrenal insufficiency (RAI) is a common finding in cirrhotic patients with severe sepsis, and increased mortality. Its significance is unknown in stable conditions. The aim of this study was to evaluate the prevalence of RAI in stable cirrhotic patients at different stages of the disease. Also, the impact of RAI on the survival was evaluated and basal cortisol levels between plasma and saliva was correlated in control subjects and cirrhotic patients. Forty seven ambulatory patients and 16 control subjects were studied. RAI was defined as a serum cortisol increase of less than 9 υg/dl from baseline after the stimulation with 250 mg of synthetic ACTH. Twenty two had Child-Pugh = 8 and 25 = 9. The prevalence of RAI in patients with stable cirrhosis was 22%. A higher incidence of RAI was observed in patients with a Child-Pugh = 9 (8/32) than in those with = 8 (3/13, p < 0.05). A correlation between salivary cortisol and basal plasma cortisol (r = 0.6, p < 0.0004) was observed. Finally, survival at 1 year (97%) and 3 years (91%) was significantly higher without RAI than those who developed this complication (79% and 51%, p < 0.05, respectively). In summary, the prevalence of RAI is frequent in patients with stable cirrhosis and that it is related to the severity of liver diseaseand increased mortality. PMID:27576278

  1. Social anxiety in orthognathic patients.

    PubMed

    Ryan, F S; Moles, D R; Shute, J T; Clarke, A; Cunningham, S J

    2016-01-01

    There is evidence that patients seeking orthognathic treatment may be motivated by social anxiety disorder (SAD). The aim of this study was to investigate SAD in orthognathic patients using the Brief Fear of Negative Evaluation Scale (BFNES) and to compare these findings with those of the general population. This was a cross-sectional, questionnaire study conducted in two parts. Firstly, a national survey was conducted to yield data for the BFNES from a large, random sample of the UK general population. Secondly, orthognathic patients completed the BFNES. The BFNES scores are reported in two formats: the original 12-item scale (O-BFNES) and a shorter eight-item version (S-BFNES). With regards to the national survey, 1196 individuals participated. The mean O-BFNES score was 29.72 (standard deviation (SD) 9.39) and S-BFNES score was 15.59 (SD 7.67). With regards to the orthognathic sample, 61 patients participated. The mean O-BFNES score was 39.56 (SD 10.35) and the mean S-BFNES score was 24.21 (SD 8.41). Orthognathic patients had significantly higher scores than the general UK population (P<0.001), and multiple linear regression revealed that age, gender, and patient status were all independent predictors of BFNES scores. From the results of this study, orthognathic patients experience significantly higher levels of social anxiety than the general population. PMID:26304605

  2. Celebrity Patients, VIPs, and Potentates

    PubMed Central

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

    2002-01-01

    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

  3. HPV Carcinomas in Immunocompromised Patients

    PubMed Central

    Reusser, Nicole M.; Downing, Christopher; Guidry, Jacqueline; Tyring, Stephen K.

    2015-01-01

    Human papillomavirus (HPV) infection is the most common sexually transmitted disease worldwide and can result in pre-malignancies or overt malignancies of the skin and mucosal surfaces. HPV-related illnesses are an important personal and public health problem causing physical, mental, sexual and financial detriments. Moreover, this set of malignancies severely affects the immunosuppressed population, particularly HIV-positive patients and organ-transplant recipients. There is growing incidence of HPV-associated anogenital malignancies as well as a decrease in the average age of affected patients, likely related to the rising number of high-risk individuals. Squamous cell carcinoma is the most common type of HPV-related malignancy. Current treatment options for HPV infection and subsequent disease manifestations include imiquimod, retinoids, intralesional bleomycin, and cidofovir; however, primary prevention with HPV vaccination remains the most effective strategy. This review will discuss anogenital lesions in immunocompromised patients, cutaneous warts at nongenital sites, the association of HPV with skin cancer in immunocompromised patients, warts and carcinomas in organ-transplant patients, HIV-positive patients with HPV infections, and the management of cutaneous disease in the immunocompromised patient. PMID:26239127

  4. Interactive Visualization for Patient-to-Patient Comparison.

    PubMed

    Nguyen, Quang Vinh; Nelmes, Guy; Huang, Mao Lin; Simoff, Simeon; Catchpoole, Daniel

    2014-03-01

    A visual analysis approach and the developed supporting technology provide a comprehensive solution for analyzing large and complex integrated genomic and biomedical data. This paper presents a methodology that is implemented as an interactive visual analysis technology for extracting knowledge from complex genetic and clinical data and then visualizing it in a meaningful and interpretable way. By synergizing the domain knowledge into development and analysis processes, we have developed a comprehensive tool that supports a seamless patient-to-patient analysis, from an overview of the patient population in the similarity space to the detailed views of genes. The system consists of multiple components enabling the complete analysis process, including data mining, interactive visualization, analytical views, and gene comparison. We demonstrate our approach with medical scientists on a case study of childhood cancer patients on how they use the tool to confirm existing hypotheses and to discover new scientific insights. PMID:24748858

  5. Quality of Doctor-Patient Communication through the Eyes of the Patient: Variation According to the Patient's Educational Level

    ERIC Educational Resources Information Center

    Aelbrecht, Karolien; Rimondini, Michela; Bensing, Jozien; Moretti, Francesca; Willems, Sara; Mazzi, Mariangela; Fletcher, Ian; Deveugele, Myriam

    2015-01-01

    Good doctor-patient communication may lead to better compliance, higher patient satisfaction, and finally, better health. Although the social variance in how physicians and patients communicate is clearly demonstrated, little is known about what patients with different educational attainments actually prefer in doctor-patient communication. In…

  6. Patient perceptions of orthognathic surgery.

    PubMed

    Flanary, C M; Barnwell, G M; Alexander, J M

    1985-08-01

    A retrospective study of ninety orthognathic surgery patients was conducted to investigate (1) their presurgical concerns and motivations, (2) their preoperative preparation for surgery, and (3) their perceptions of the postsurgical outcome. All subjects completed a twenty-three-item questionnaire and Rotter's Locus of Control Inventory. Statistical date analyses were performed by means of frequency distributions, chi-square, Spearman's r, and Fisher's exact probability tests. The results are presented as thirteen tentative conclusions categorized into three broad areas: motivations and concerns, presurgical preparation, and postsurgical outcome. In the area of motivations and concerns, those with primarily esthetic motivations have less initial reticence toward having orthognathic surgery and less difficulty adjusting to their new appearance than those with strong functional incentives. Younger patients and those patients with strong cosmetic motivations are less concerned about surgical risks. Under the category of presurgical preparation, more females than males desire to speak to a previous orthognathic surgery patient. Patients who receive inadequate explanation of the surgical procedure are more likely to be emotionally unprepared. One of the leading factors in patient dissatisfaction with surgery is the patient's experience of postoperative "surprises." In the area of postsurgical outcome, two-jaw operations precipitate more pain complaints than single-arch procedures. With time, however, patients tend to forget the degree of postoperative pain. Maxillary surgical procedures lead to less severe pain complaints than mandibular procedures, but there are more initial complaints of breathing difficulties and sinus problems following maxillary procedures. Surgical goal fulfillment does not guarantee that a patient would re-elect to have the treatment. PMID:3861099

  7. Patient satisfaction with antihypertensive therapy.

    PubMed

    Chen, K; Chiou, C-F; Plauschinat, C A; Frech, F; Harper, A; Dubois, R

    2005-10-01

    The objective of the study was to assess factors associated with treatment satisfaction among patients receiving antihypertensive therapy. A weighted cross-sectional online survey was conducted with hypertensive patients participating in a chronic disease panel in the US. Patients on monotherapy with medications from the following classes were identified: ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta blockers (BBs), calcium channel blockers (CCBs), and diuretics. The control group included patients without treatment. Pairwise comparisons between groups were conducted for factors that may affect patients' satisfaction. The study population had a mean age of 54.7+/-14.2 years and was 56.7% female. Participants with blood pressure (BP) controlled to JNC 7 guidelines were more satisfied with their medication than those with uncontrolled BP (90.3 vs 71.5%, P<0.05). Patients who had not experienced adverse events had higher satisfaction than patients experiencing adverse events (90.9 vs 75.8%, P<0.05). The most frequently self-reported adverse events were frequent urination, sexual dysfunction, and fatigue ranging from 7.0 to 9.6% across classes. The adverse event rates differed by class and were lowest among the ARBs. Patients on ARBs were the most likely to have switched from a previous antihypertensive class as compared to other classes (57.1% ARBs vs 49.8% ACEIs, 38.7% diuretics, 36.3% CCBs, and 31.7% BBs). Physician recommendation was the most common reason for switching. In conclusion, the ability to effectively treat hypertension depends upon a patient's satisfaction with antihypertensive therapy, which may be improved by achieving BP control and minimizing the occurrence of adverse events. PMID:15951740

  8. Marginal ulcer in achlorhydric patients.

    PubMed Central

    Tauxe, R V; Wright, L F; Hirschowitz, B I

    1975-01-01

    Recurrent gastrojejunal ulceration is reported in three patients with histamine-fast achlorhydria. In none of these patients was extruding suture material responsible for the ulceration. However, all three patients had a history of alcohol abuse, and one abused aspirin as well. These cases demonstrate that achlorhydria does not protect against anastomotic ulceration. It is suggested that surgical manipulation produces an increased susceptibility to mucosal damage, and that it is erroneous to consider all anastomotic ulceration as a continuation or recurrence of acid peptic disease. PMID:1130864

  9. Comorbidities in patients with spondyloarthritis.

    PubMed

    van der Horst-Bruinsma, Irene E; Nurmohamed, Michael T; Landewé, Robert B M

    2012-08-01

    Chronic inflammatory spondyloarthritis involves axial symptoms of the spine and sacroiliac joints, or peripheral arthritis. Many patients suffer from extra-articular manifestations. With acute anterior uveitis, rapid treatment prevents synechiae. Other organs can be involved. Treatment includes exercise, nonsteroidal antiinflammatory drugs (if insufficient response, tumor necrosis factor blockers), and (with peripheral arthritis) sulfasalazine. Patients with ankylosing spondylitis have comorbidities and increased cardiovascular risk. For uveitis or inflammatory bowel disease, patients should be referred to an ophthalmologist or gastroenterologist. Cardiovascular risk may originate from atherosclerotic disease and cardiac manifestations. Epidemiological studies should be conducted before echocardiogram screening and cardiovascular risk management. PMID:23083753

  10. Respiratory Emergencies in Geriatric Patients.

    PubMed

    Tyler, Katren; Stevenson, Dane

    2016-02-01

    Acute dyspnea in older patients is a common presentation to the emergency department. Acute dyspnea in older adults is often the consequence of multiple overlapping disorders, such as pneumonia precipitating acute heart failure. Emergency physicians must be comfortable managing patients with acute dyspnea of uncertain cause and varying goals of care. In addition to the important role noninvasive ventilation (NIV) plays in full resuscitation, NIV can be useful as a method of providing supportive or nearly fully supportive care while more information is gathered from the patients and their loved ones. PMID:26614240

  11. Special Considerations in Trauma Patients.

    PubMed

    Abraham, Michael K; Aquino, Patrick R; Kuo, Dick C

    2015-11-01

    The emergent management of a traumatic injury can be an extremely intense situation. These assessments can be even more difficult when patients have an underlying psychiatric condition. After a protocoled evaluation of the traumatic injuries, the psychological manifestation of diseases can be addressed. The appropriate use of physical or chemical restraints to facilitate the work-up is paramount in the ability of the provider to protect patients and staff from agitated and traumatized patients. The emergency medicine provider should have a low threshold for including psychiatry in the treatment plans, as the long-term sequelae of these entities require specialized treatment. PMID:26493528

  12. Erectile dysfunction in COPD patients.

    PubMed

    Turan, Onur; Ure, Iyimser; Turan, Pakize Ayse

    2016-02-01

    Sexual dysfunction is a common problem in chronic obstructive pulmonary disease (COPD). We aimed to assess the presence of erectile dysfunction (ED) in COPD patients. Ninety-three outpatients who had been diagnosed as COPD and followed in Bolvadin State Hospital, Afyon, Turkey, were included in the study. All patients underwent pulmonary function tests and arterial blood gas analysis. They completed International Physical Activity Questionnaire (IPAQ), Medical Research Council (MRC) Dyspnea Scale, Short Form 36-item Scale (SF-36), and International Index of Erectile Function (IIEF) Questionnaire. The mean age of 10 (10.8%) mild, 46 (49.5%) moderate, 28 (30.1%) severe, and 9 (9.7%) very severe COPD patients was 61.4 ± 9.8 years. Varying degrees of ED were detected in 67.7% of COPD patients. All patients with hypoxemia had ED. IPAQ score and all SF-36 parameters were low in patients with ED, while MRC score was high. Forced expiratory volume in one second, forced vital capacity, partial pressure of oxygen in blood, oxygen (O2) saturation, IPAQ score, and role-physical parameters were statistically low in ED patients (p = 0.04, 0.02, <0.01, <0.01, 0.02, and 0.04, respectively); MRC score was statistically higher in patients with ED (p = 0.02). Patients with moderate and severe ED had statistically lower score of mental health (p < 0.01 and p = 0.02, respectively). There was a positive correlation between IIEF score and IPAQ scores (p < 0.01), MRC scores (p = 0.01), general health (p < 0.01), role-physical (p < 0.01), role-emotional (p < 0.01), physical functioning (p < 0.01), and mental health (p < 0.01) parameters in SF-36. ED is frequently seen in COPD patients. Hypoxemia, smoking, and limitation of physical activity are thought to be associated with ED in COPD as mechanisms. Quality of life and the functional capacity are negatively affected with the presence of ED. It is important for a physician to question the sexual functions in patients with COPD. The

  13. Neurology of the geriatric patient.

    PubMed

    Fenner, W R

    1988-05-01

    Owing to improvements in health care, more animals are living to advanced ages. Many abnormal neurologic conditions can affect these patients, but those most commonly associated with advancing years include degenerative, neoplastic, and idiopathic processes. An understanding of the "normal" age-related changes seen on a neurologic examination must be kept in mind when evaluating geriatric patients. Special care and consideration of the patient and client are often required in managing these cases, especially because treatment protocols are often unsuccessful or do not exist, resulting in a prognosis that is often poor at best. PMID:3289252

  14. Patient puzzle. Use systematic assessment to detect & correct patient conditions.

    PubMed

    Stoy, W A

    2001-01-01

    Medic 27 responds to a report of a fall victim at 27 West Pinnacle Lane. En route, the crew learns from dispatch that the patient fell approximately 25 feet from the roof of a three-story structure onto the roof of an adjacent garage. The caller reports the patient "going in and out of consciousness." The EMS crew requests the dispatch of a rescue unit and ladder company to assist on scene and the placement of a medical helicopter on standby. On scene, the patient's wife reports her husband accidentally disturbed a hornets' nest as he secured a weather vane to the top of the family home. She says the hornets stung her husband repeatedly. In his attempt to avoid the stings, his movements jarred the ladder, causing him to fall to the roof below. As you walk to the side of the patient's home, his wife adds that her husband has a cardiac condition and now complains of chest pain and trouble breathing. You wonder what you'll find when you reach the victim. Is he a medical patient with traumatic injuries or a trauma patient with medical complications? PMID:11213605

  15. Evidence-based patient education: knowledge transfer to endodontic patients.

    PubMed

    Sorrell, John T; McNeil, Daniel W; Gochenour, Lori L; Jackson, C Russell

    2009-11-01

    Evidence-based treatment is emphasized in oral health care, but there has been less focus on empirically demonstrating the effects of patient education. Attempts to educate patients must be empirically demonstrated in order to provide evidence-based guidance to practitioners and educators. We conducted two studies that assessed information acquisition during five-minute audiovisual films on oral hygiene procedures, endodontic procedures, and fear about pain during root canal therapy. A fifteen-item Dental Knowledge Questionnaire (DKQ), with three subscales each focusing on the content of one of the films, was developed and psychometrically evaluated. Study 1 included 268 undergraduates; study 2 involved 104 endodontic patients. Participants completed the DKQ, viewed one of the three films, and repeated the questionnaire. The effects of information on knowledge were assessed using 3 (film group) X 3 (subscale of the DKQ) X 2 (time) repeated measures ANOVAs. Scores improved in a content-specific fashion relevant to the film viewed among undergraduates, F(4, 263)=211.33, p<.001, partial eta(2)=.62 and endodontic patients, F(4, 99)=87.22, p<.001, partial eta(2)=.63. The results provide evidence for using brief informational film as an efficacious method to increase patient knowledge, at least in the short term. The DKQ is proposed as a tool to assess patient knowledge in the arenas of oral hygiene and endodontics. PMID:19910479

  16. Patient participation in pressure injury prevention: giving patient's a voice.

    PubMed

    Latimer, Sharon; Chaboyer, Wendy; Gillespie, Brigid

    2014-12-01

    Pressure injuries burden patients and healthcare organisations, with some preventative practices having little impact on prevalence reduction. Patient participation in care may be an effective pressure injury prevention strategy, yet patient preferences are unknown. The aim of this interpretive study was to describe patients' perceptions of their current and future role in pressure injury prevention. Semi-structured interviews were conducted with 20 adult inpatients recruited from four medical units, at two Australian metropolitan hospitals. Interview data were analysed using content analysis, with three categories emerging: 'experiencing pressure injuries'; 'participating in pressure injury prevention'; and 'resourcing pressure injury prevention and treatment'. These categories reflect the complex nature of participants' pressure injury experience. The findings suggest participants gather pressure injury knowledge from first-hand and vicarious experience; knowledge they bring to hospital. Most participants preferred a proactive pressure injury prevention role. Many identified barriers in the healthcare environment that impeded their participation and affected their experience of pressure injuries and pressure injury prevention. If patient participation as a pressure injury prevention strategy is to be considered, nurses and organisations need to view patients as partners. PMID:24117711

  17. [Coronary angioplasty in elderly patients].

    PubMed

    Liistro, Francesco; Colombo, Antonio

    2002-01-01

    Developed nations are experiencing an unprecedented growth in the number of elderly citizens. Thanks to the modernization of both society and medical care, over the past century, life expectancy in most countries has nearly doubled. The elderly (80 years or over) represent the fastest-growing segment of our population. Owing to their age, the elderly are more afflicted with chronic diseases, including coronary artery disease. Recently, clinicians became more aggressive in the use of invasive cardiovascular diagnostic tests in these patients. With regard to younger patients, we have a wealth of data from large, randomized trials that defined which subsets of patients benefit from revascularization therapies. However, because the very elderly were severely underrepresented in these randomized studies, we have almost no information concerning the choice of treatment in these patients. Initial results of percutaneous revascularization procedures in elderly patients come from retrospective analysis performed during the pre-stent era. In these studies a procedural mortality risk 5-fold higher in patients > 80 years compared with those < 60 is reported. With the advent of coronary stenting, a significant increase in the rate of procedural success and a reduction in the incidence of procedural mortality, acute myocardial infarction and emergency coronary artery bypass grafting were observed also in the elderly. These initial positive results prompted physicians to treat patients with impaired clinical conditions and with unfavorable angiographic characteristics, resulting in a long-term freedom from major adverse cardiac events comparable to those observed in younger patients (78% in patients < 70 years vs 75% in patients > 80 years). The comparison between the percutaneous approach and the surgical approach to coronary artery disease in the elderly has its major limitation in the lack of data from randomized trials. The available information suggests similar results with

  18. Effects of comfort warming on preoperative patients.

    PubMed

    Wagner, Doreen; Byrne, Michelle; Kolcaba, Katharine

    2006-09-01

    THERMAL COMFORT IS ONE DIMENSION of overall patient comfort, and it usually is addressed by covering the patient with warmed cotton blankets. WARMING HELPS A PATIENT maintain normothermia and appears to decrease patient anxiety. AN STUDY WAS CONDUCTED in a preoperative setting to compare the effects of preoperative warming with warmed cotton blankets versus patient-controlled warming gowns on patients' perceptions of thermal comfort and anxiety. BOTH WARMING INTERVENTIONS had a positive effect on patients' thermal comfort and sense of well-being. Patients who used the patient-controlled warming gown also experienced a significant reduction in preoperative anxiety. PMID:17004666

  19. 38 CFR 17.33 - Patients' rights.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Patient Rights § 17.33 Patients' rights. (a) General. (1) Patients have a right to be treated with dignity... privacy with regard to their personal needs. (2) Patients have a right to receive, to the extent of... purposes. (4) No patient in the Department of Veterans Affairs medical care system, except as...

  20. 38 CFR 17.33 - Patients' rights.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Patient Rights § 17.33 Patients' rights. (a) General. (1) Patients have a right to be treated with dignity... privacy with regard to their personal needs. (2) Patients have a right to receive, to the extent of... purposes. (4) No patient in the Department of Veterans Affairs medical care system, except as...

  1. 38 CFR 17.33 - Patients' rights.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Patient Rights § 17.33 Patients' rights. (a) General. (1) Patients have a right to be treated with dignity... privacy with regard to their personal needs. (2) Patients have a right to receive, to the extent of... purposes. (4) No patient in the Department of Veterans Affairs medical care system, except as...

  2. 38 CFR 17.33 - Patients' rights.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Patient Rights § 17.33 Patients' rights. (a) General. (1) Patients have a right to be treated with dignity... privacy with regard to their personal needs. (2) Patients have a right to receive, to the extent of... purposes. (4) No patient in the Department of Veterans Affairs medical care system, except as...

  3. Developing patient-centered teams: The role of sharing stories about patients and patient care.

    PubMed

    Bennett, Ariana H; Hassinger, Jane A; Martin, Lisa A; Harris, Lisa H; Gold, Marji

    2015-09-01

    Research indicates that health care teams are good for staff, patients, and organizations. The characteristics that make teams effective include shared objectives, mutual respect, clarity of roles, communication, trust, and collaboration. We were interested in examining how teams develop these positive characteristics. This paper explores the role of sharing stories about patients in developing patient-centered teams. Data for this paper came from 1 primary care clinic as part of a larger Providers Share Workshop study conducted by the University of Michigan. Each workshop included 5 facilitated group sessions in which staff met to talk about their work. This paper analyzes qualitative data from the workshops. Through an iterative process, research team members identified major themes, developed a coding scheme, and coded transcripts for qualitative data analysis. One of the most powerful ways group members connected was through sharing stories about their patients. Sharing clinical cases and stories helped participants bond around their shared mission of patient-centered care, build supportive relationships, enhance compassion for patients, communicate and resolve conflict, better understand workflows and job roles, develop trust, and increase morale. These attributes highlighted by participants correspond to those documented in the literature as important elements of teambuilding and key indicators of team effectiveness. The sharing of stories about patients seems to be a promising tool for positive team development in a primary care clinical setting and should be investigated further. PMID:26348238

  4. Helping Patients To Quit Smoking

    PubMed Central

    Bass, Frederic

    1989-01-01

    Years ago, the tobacco leaf offered its users many social and ceremonial benefits. But today, throughout the world, the manufactured cigarette wreaks biological havoc. Clinically, physicians can make a small, but significant, contribution to their patients' stopping smoking. Family physicians who want to offer systematic aid to their smoking patients should assess the amount of time and energy they are willing to invest in patients' smoking and the probable rewards of such efforts. Behavioural change comprises four stages: a pre-motivational phase, a motivational phase, a behavioural-change phase, and a maintenance phase. Anyone who has ever smoked belongs to one of these phases and should be treated accordingly. Paradoxically, the physician should support consonant smoking (the patient freely choosing to smoke) except when the smoker is actively engaged in changing behaviour. PMID:21248907

  5. Implant rehabilitation in bruxism patient

    PubMed Central

    Goiato, Marcelo Coelho; Sonego, Mariana Vilela; dos Santos, Daniela Micheline; da Silva, Emily Vivianne Freitas

    2014-01-01

    A white female patient presented to the university clinic to obtain implant retained prostheses. She had an edentulous maxillary jaw and presented three teeth with poor prognosis (33, 34 and 43). The alveolar bone and the surrounding tissues were healthy. The patient did not report any relevant medical history contraindicating routine dental treatment or implant surgery, but self-reported a dental history of asymptomatic nocturnal bruxism. The treatment plan was set and two Branemark protocols supported by six implants in each arch were installed after a 6-month healing period. A soft occlusal splint was made due to the patient's history of bruxism, and the lack of its use by the patient resulted in an acrylic fracture. The prosthesis was repaired and the importance of using the occlusal splint was restated. In the 4-year follow-up no fractures were reported. PMID:24907215

  6. Examination of the adolescent patient.

    PubMed

    Hampton, H L

    2000-03-01

    Adolescent patients need knowledge and motivation to practice a healthy lifestyle. The provider of adolescent health care is uniquely qualified to provide factual health information and practical advice. Enlisting parental support for confidential adolescent health services usually is not problematic when parents and health care providers share common goals and responsibility. The health care provider must develop rapport to foster high-risk health behavior disclosure and must promote health messages that are stronger than those received from peers, television, movies, and magazines. Adolescents who elect to abstain from sexual activity need as much support as sexually active patients. Depression, substance abuse, and eating disorders must be recognized and treated. Preventative health care services for adolescents can be optimized when office staff understand the special needs of these young women. The physician's concerns regarding the health of adolescent patients will be welcomed by patients, their parents, and the community. PMID:10693179

  7. Time out for patient safety.

    PubMed

    Meginniss, Anne; Damian, Frances; Falvo, Francine

    2012-01-01

    "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

  8. Should Immunocompromised Patients Have Pets?

    PubMed Central

    Steele, Russell W.

    2008-01-01

    Purpose: To evaluate the risks and benefits of pet ownership by immunodeficient patients, focusing primarily on organisms that colonize animals and are transmitted to humans. Those diseases that are known to be progressive or more severe in patients with altered immune function are emphasized. Methods: A review of the medical and veterinary literature pertaining to zoonoses transmitted by domestic animals was completed. Information pertaining to issues involving immunosuppressed patients including AIDS was carefully evaluated and summarized for inclusion. Results: There are significant clinical and psychosocial benefits to pet ownership. However, numerous diseases can be acquired from these animals which may be more severe in immunocompromised individuals. Conclusion: Simple guidelines for pet ownership by immunosuppressed patients can be implemented to reduce their risk of disease and allow them to safely interchange with their pets. PMID:21603465

  9. Which therapy for which patient?

    PubMed

    Pierangeli, G; Cevoli, S; Sancisi, E; Grimaldi, D; Zanigni, S; Montagna, P; Cortelli, P

    2006-05-01

    Prophylactic treatment is mainly intended to reduce the frequency of migraine attacks, enhance response to acute medications, improve patient function and reduce disability. Sufficient evidence and consensus exist to recommend propranolol, timolol, amitriptyline, pizotifen, divalproex, sodium valproate and topiramate as first line agents for migraine prevention. These drugs can halve the frequency of attacks in 50% of patients. The anticipated benefit must be weighed against the adverse effects associated with each agent in determining the optimal preventive regimen for individual patients considering any comorbid conditions that are often present. The decision to treat and the choice of prophylactic drug must be taken with the patient. It is important to balance expectations and therapeutic realities for each particular drug. Recent data on the effect of prophylactic treatment on trigeminovascular activation and on cortical spreading depression emphasise the importance of developing research on migraine-preventive drugs. PMID:16688621

  10. The patient with daily headaches.

    PubMed

    Maizels, Morris

    2004-12-15

    The term "chronic daily headache" (CDH) describes a variety of headache types, of which chronic migraine is the most common. Daily headaches often are disabling and may be challenging to diagnose and treat. Medication overuse, or drug rebound headache, is the most treatable cause of refractory daily headache. A pathologic underlying cause should be considered in patients with recent-onset daily headache, a change from a previous headache pattern, or associated neurologic or systemic symptoms. Treatment of CDH focuses on reduction of headache triggers and use of preventive medication, most commonly anti-depressants, antiepileptic drugs, and beta blockers. Medication overuse must be treated with discontinuation of symptomatic medicines, a transitional therapy, and long-term prophylaxis. Anxiety and depression are common in patients with CDH and should be identified and treated. Although the condition is challenging, appropriate treatment of patients with CDH can bring about significant improvement in the patient's quality-of-life. PMID:15617293

  11. Polypharmacy in heart failure patients.

    PubMed

    Mastromarino, Vittoria; Casenghi, Matteo; Testa, Marco; Gabriele, Erica; Coluccia, Roberta; Rubattu, Speranza; Volpe, Massimo

    2014-06-01

    In heart failure (HF), the progressive use of multiple drugs and a complex therapeutic regimen is common and is recommended by international guidelines. With HF being a common disease in the elderly, patients often have numerous comorbidities that require additional specific treatment, thus producing a heavy pill burden. Polypharmacy, defined as the chronic use of five or more medications, is an underestimated problem in the management of HF patients. However, polypharmacy has an important impact on HF treatment, as it often leads to inappropriate drug prescription, poor adherence to pharmacological therapies, drug-drug interactions, and adverse effects. The growing complexity of HF patients, whose mean age increases progressively and who present multiple comorbidities, suggests the need for newer models of primary care to improve the management of HF patients. Self-care, telemonitoring, and natriuretic peptide-guided therapy represent promising new HF care models to face the complexity of the disease and its therapeutic regimen. PMID:24493574

  12. Turning patients over in bed

    MedlinePlus

    ... This helps the skin stay healthy and prevents bedsores. Turning a patient is a good time to ... M, et al. Risk assessment and prevention of pressure ulcers: a clinical practice guideline from the American College ...

  13. Turning patients over in bed

    MedlinePlus

    ... so the person is not at risk of rolling out of the bed. The patient's bottom arm ... M, et al. Risk assessment and prevention of pressure ulcers: a clinical practice guideline from the American ...

  14. [The nurse and patient's nudity].

    PubMed

    dos Santos, Regina Maria; Viana, Ivea Rayane M N; da Silva, Josefa Rita; Trezza, Maria Cristina Soares Figueiredo; Leite, Joséte Luzia

    2010-01-01

    This is a qualitative study about the relationship among nurses of a university hospital and their patients when they need to undress those patients to take care. The purpose was to analyze speech of seven nurses in this situation. The information was taken by transcribing the semi-structured interviews which were analyzed according Michel Foucault's thought. The results demonstrated that the relationship among nurses and patients at the time when nudity is needed to perform nursing care is full of power, to which the nurses don't feel always prepared. Also the nurses don't think that, acting as they act, they exert power over the patients. It is suggested to Nursing schools to perform seminars about the care with the naked body. PMID:21308217

  15. Hospitalized Patients and Fungal Infections

    MedlinePlus

    ... but can also be caused by fungi. Hospital construction. Hospital staff do everything they can to prevent ... patients staying at hospitals where there is ongoing construction or renovation. 5 This is thought to be ...

  16. [Perioperative Management of PD Patients].

    PubMed

    Reichmann, H

    2016-07-01

    Both patients and caregivers but also treating physicians are concerned about complications along with surgical interventions. A major problem is abrupt cessation of anti-Parkinson medication, which leads to manifold disturbances, sometimes even to an akinetic crisis. There are several means to guarantee continuous dopaminergic stimulation even in patients that are not allowed to take medication orally before they undergo surgery. Amongst others rectally applied levodopa, amantadine infusions, and especially the use of a rotigotine patch are good means to overcome oral intake. Perioperative management is important due to the fact that in Germany alone each year more than 10 000 PD patients undergo surgery. Main reasons for this are fractures, but also elective interventions. Further emergency situations that cause treatment as an inpatient are psychosis, motoric disability, but also pneumonia and cardiovascular disturbances. In contrast PD patients suffer less often from cancer. PMID:27276074

  17. Noma in an immunocompromised patient.

    PubMed

    Silva, Igor Henrique Morais; Faria, Andreza Barkokebas S de; Fonseca, Deborah Daniela Diniz; Aguiar, Carlos Menezes; Carvalho, Alessandra Tavares; Gueiros, Luiz Alcino; Leao, Jair Carneiro

    2013-01-01

    Noma (also known as cancrum oris) is classified by the World Health Organization as a necrotizing ulcerative stomatitis, an invasive acute infection which affects the orofacial tissues. Patients who are subject to such risk factors as severe malnutrition or alteration of the immune system are predominantly affected. This article presents a case of noma in a 62-year-old immunocompromised patient with pain and tooth mobility in the mandibular region, ulceration, bleeding, gingival inflammatory secretion, and oral malodor. The signs and symptoms were controlled only after the intravenous administration of 500 mg tid of imipenem/cilastatin sodium and 2 g qd of vancomycin. After infection control was maintained, the patient was directed to surgery for removal of bone sequestration and curettage of the maxillary sinus. The patient was prescribed 1 g qd of oral clindamycin for 3 months postsurgery. PMID:24192747

  18. Transfusion medicine in trauma patients

    PubMed Central

    Murthi, Sarah B; Dutton, Richard P; Edelman, Bennett B; Scalea, Thomas M; Hess, John R

    2011-01-01

    Injured patients stress the transfusion service with frequent demands for uncrossmatched red cells and plasma, occasional requirements for large amounts of blood products and the need for new and better blood products. Transfusion services stress trauma centers with demands for strict accountability for individual blood component units and adherence to indications in a clinical field where research has been difficult, and guidance opinion-based. New data suggest that the most severely injured patients arrive at the trauma center already coagulopathic and that these patients benefit from prompt, specific, corrective treatment. This research is clarifying trauma system requirements for new blood products and blood-product usage patterns, but the inability to obtain informed consent from severely injured patients remains an obstacle to further research. PMID:21083009

  19. Preventing Infections in Cancer Patients

    MedlinePlus

    ... 14 of these patients dies. What Is an Infection? You get an infection when germs enter your ... the flu. How Does the Body Normally Fight Infections? The immune system helps your body protect itself ...

  20. Corneal temperature in schizophrenia patients.

    PubMed

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

    2005-12-01

    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

  1. Patients' perceptions of psychotropic drugs

    PubMed Central

    Helman, Cecil G.

    1981-01-01

    This pilot study examined patients' perceptions of, and attitudes towards, psychotropic drug-taking. Fifty chronic users of benzodiazepines in two Middlesex group practices were interviewed, and data were collected on their knowledge, experience and expectations of these drugs. The data suggest that psychotropic drug-taking has become an important part of many patients' self-image and of their social relationships, and that these factors should be taken into account when dealing with psychological dependence on psychotropic drugs. PMID:7265056

  2. [Patients, doctors and the internet].

    PubMed

    Jeannot, Jean Gabriel; Bischoff, Thomas

    2015-05-13

    The majority of the Swiss population uses the internet to seek information about health. The objective is to be better informed, before or after the consultation. Doctors can advise their information-seeking patients about high quality websites, be it medical portals or websites dedicated to a specific pathology. Doctors should not see the internet as a threat but rather as an opportunity to strengthen the doctor-patient relationship. PMID:26118229

  3. Is My Patient An Athlete?

    PubMed Central

    Bullard, Jack

    1974-01-01

    This article outlines the ways in which the practice of medicine is affected by patients' participation in sports, or indeed any form of physical exercise. Several instances are cited where the patient's need for a quick recovery will materially affect the treatment he is given. The family physician must be aware of these instances, from the post coronary exercise program to premenstrual tension in an Olympic athlete. PMID:20469053

  4. Adenomyosis: What the Patient Needs.

    PubMed

    Alabiso, Giulia; Alio, Luigi; Arena, Saverio; Barbasetti di Prun, Allegra; Bergamini, Valentino; Berlanda, Nicola; Busacca, Mauro; Candiani, Massimo; Centini, Gabriele; Di Cello, Annalisa; Exacoustos, Caterina; Fedele, Luigi; Fuggetta, Eliana; Gabbi, Laura; Geraci, Elisa; Imperiale, Ludovica; Lavarini, Elena; Incandela, Domenico; Lazzeri, Lucia; Luisi, Stefano; Maiorana, Antonio; Maneschi, Francesco; Mannini, Luca; Mattei, Alberto; Muzii, Ludovico; Pagliardini, Luca; Perandini, Alessio; Perelli, Federica; Pinzauti, Serena; Porpora, Maria Grazia; Remorgida, Valentino; Leone Roberti Maggiore, Umberto; Seracchioli, Renato; Solima, Eugenio; Somigliana, Edgardo; Tosti, Claudia; Venturella, Roberta; Vercellini, Paolo; Viganò, Paola; Vignali, Michele; Zannoni, Letizia; Zullo, Fulvio; Zupi, Errico

    2016-01-01

    A panel of experts in the field of endometriosis expressed their opinions on management options in a 28-year-old patient, attempting pregnancy for 1 year, with severe cyclic pelvic pain and with clinical examination and imaging techniques suggestive of adenomyosis. Many questions this paradigmatic patient may pose to the clinician are addressed, and all clinical scenarios are discussed. A decision algorithm derived from this discussion is also proposed. PMID:26772777

  5. SUICIDAL COMMUNICATION IN PSYCHIATRIC PATIENTS

    PubMed Central

    Anand, R.; Trivedi, J.K.; Gupta, S.C.

    1983-01-01

    In this enquiry a cross-sectional study of hospitalized psychiatric patients was undertaken to assess prevalence and nature of suicidal behaviour. We have been able to delineate these subjects into three categories i.e. non-communicators, partial communicators and definite communicators on the basis of their scores upon 31ucid.il intent questionnaire. A follow up study of these patients which is in progress may further provide knowledge about relationship between predictive criterion and their final outcome. PMID:21847269

  6. Inspiration of psychotherapists by patients.

    PubMed

    Messner, E

    1976-12-01

    Many patients possess such exemplary traits and virtues that their psychotherapists are inspired to emulate them. This process can benefit the clinician and reinforce the therapeutic alliance, rapport, and the spirit of reciprocity; however, it can also arouse responses by the clinician that are therapeutically detrimental. Awareness of this hazard can enable the clinican to avert it and enhance the benefits provided by the patient's outstanding strengths. PMID:984249

  7. Patient Simulators Train Emergency Caregivers

    NASA Technical Reports Server (NTRS)

    2014-01-01

    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.

  8. Psychoeducation. Patient education gets respect.

    PubMed

    London, Fran

    2008-04-01

    Even those who are not psychiatric nurses find themselves caring for patients with psychiatric disorders. Adults with a mental health and/or substance abuse diagnosis accounted for 1 of 4 hospital stays in 2004. Whether the patient's problem is physical, mental, or both, most care is self-care. Psychoeducation improves health outcomes by optimizing self-care skills, engaging family and community supports, and promoting early recognition of problems and appropriate interventions. PMID:18408511

  9. Donor commitment and patient needs.

    PubMed

    Bakken, R; van Walraven, A-M; Egeland, T

    2004-01-01

    The article discusses views and recommendations of the World Marrow Donor Association concerning ethical issues related to the donation of hematopoietic stem cell products with respect to recruitment, evaluation, workup, and follow-up of unrelated donors. Particular emphasis is placed upon commitment of individual donors, in particular, with respect to the needs of patients to find HLA-matched donors, who may be asked to donate stem cell and other cell products more than once for given patients. PMID:14628078

  10. Patient selection: indications and contraindications.

    PubMed

    Choy, D S; Botsford, J; Black, W A

    1995-06-01

    Patient selection is critical to the success of PLDD. In general, the herniation must have continuity with the parent disc; rupture of the annulus is not a contraindication. Several other orthopedic conditions constitute absolute or relative contraindications. All patients must be individualized. Our criteria for inclusion is undergoing continuing change. What is unacceptable now may, with modifications, become acceptable in the future. It is important not to adopt a fixed position at this early stage of PLDD. PMID:10150640

  11. Hypnotherapy and the Suicidal Patient

    PubMed Central

    Glick, Daniel

    1973-01-01

    Three cases are presented in which a family physician treats a suicidal patient by the hypnotherapeutic method described. It is postulated that such a method may be quick, effective, and relatively safe method for a diagnostic and therapeutic approach in family practice. In the hypnotic state, the patient is hypersuggestible and can accept suggestions which meet her unconscious needs to be loved as an individual within the milieu of the ego state at the time her psychopathology occurred. PMID:20468906

  12. [Anal cancer in HIV patients].

    PubMed

    Quéro, Laurent; Duval, Xavier; Abramowitz, Laurent

    2014-11-01

    Despite effective highly active antiretroviral treatment, anal cancer incidence has recently strongly increased in HIV-infected population. Treatment strategy in HIV-infected patients does not differ from general population. HIV-infected patients treated by chemo-radiotherapy are exposed to high-grade toxicities and should be closely monitored to deliver the optimal treatment. Close collaboration between oncologist and infectiologist is highly recommended to adjust antiretroviral therapy if necessary. PMID:25418596

  13. Nutritional Considerations for Cancer Patients

    PubMed Central

    Chen, Angela

    1985-01-01

    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

  14. Leiomyomas in patients receiving Tamoxifen.

    PubMed

    Leo, L; Lanza, A; Re, A; Tessarolo, M; Bellino, R; Lauricella, A; Wierdis, T

    1994-01-01

    In literature there have been only 8 cases of unavoidable laparotomy due to uterine leiomyomas performed in patients with breast cancer on Tamoxifen (TAM). Our article describes two cases of rapidly growing leiomyomas in patients treated with TAM: one of these underwent abdominal hysterectomy while the second stopped taking TAM and began therapy with Triptorelin. This therapeutical alternative could be a useful choice. PMID:8070124

  15. Hypothermia and the trauma patient

    PubMed Central

    Kirkpatrick, Andrew W.; Chun, Rosaleen; Brown, Ross; Simons, Richard K.

    Hypothermia has profound effects on every system in the body, causing an overall slowing of enzymatic reactions and reduced metabolic requirements. Hypothermic, acutely injured patients with multisystem trauma have adverse outcomes when compared with normothermic control patients. Trauma patients are inherently predisposed to hypothermia from a variety of intrinsic and iatrogenic causes. Coagulation and cardiac sequelae are the most pertinent physiological concerns. Hypothermia and coagulopathy often mandate a simplified approach to complex surgical problems. A modification of traditional classification systems of hypothermia, applicable to trauma patients is suggested. There are few controlled investigations, but clinical opinion strongly supports the active prevention of hypothermia in the acutely traumatized patient. Preventive measures are simple and inexpensive, but the active reversal of hypothermia is much more complicated, often invasive and controversial. The ideal method of rewarming is unclear but must be individualized to the patient and is institution specific. An algorithm reflecting newer approaches to traumatic injury and technical advances in equipment and techniques is suggested. Conversely, hypothermia has selected clinical benefits when appropriately used in cases of trauma. Severe hypothermia has allowed remarkable survivals in the course of accidental circulatory arrest. The selective application of mild hypothermia in severe traumatic brain injury is an area with promise. Deliberate circulatory arrest with hypothermic cerebral protection has also been used for seemingly unrepairable injuries and is the focus of ongoing research. PMID:10526517

  16. Peripapillary Retinoschisis in Glaucoma Patients

    PubMed Central

    Bayraktar, Serife; Cebeci, Zafer; Kabaalioglu, Melis; Ciloglu, Serife; Kir, Nur; Izgi, Belgin

    2016-01-01

    Purpose. To investigate peripapillary retinoschisis and its effect on retinal nerve fiber layer (RNFL) thickness measurements by using spectral-domain optical coherence tomography (SD-OCT) in glaucomatous eyes. Methods. Circumpapillary RNFL (cpRNFL) B-scan images of 940 glaucoma patients (Group 1) and 801 glaucoma-suspect patients (Group 2) obtained by SD-OCT were reviewed. The structural and clinical characteristics of the retinoschisis were investigated. The RNFL thickness measurements taken at the time of retinoschisis diagnosis and at the follow-up visits were also compared. Results. Twenty-nine retinoschisis areas were found in 26 of the 940 glaucoma patients (3.1%) in Group 1 and seven areas were found in 801 patients (0.87%) in Group 2. In glaucomatous eyes, the retinoschisis was attached to the optic disc and overlapped with the RNFL defect. At the time of retinoschisis, the RNFL thickness was statistically greater in the inferior temporal quadrant when compared with the follow-up scans (p < 0.001). No macular involvement or retinal detachment was observed. Conclusion. The present study investigated 33 peripapillary retinoschisis patients. Increase in RNFL thickness measurements was observed at the time of retinoschisis. It is important to examine the cpRNFL B-scan images of glaucoma patients so that the RNFL thickness is not overestimated. PMID:27069674

  17. [Fertility in testicular cancer patients].

    PubMed

    Shin, Takeshi; Miyata, Akane; Arai, Gaku; Okada, Hiroshi

    2015-03-01

    Testicular cancer(TC)is the most common and curable cancer affecting men of reproductive age. Successful treatment approaches have resulted in longer life expectancy in TC survivors. The most frequently used treatment for TC is a combination of inguinal orchiectomy, and either radiotherapy or cisplatin-based chemotherapy. In many TC patients, sperm quality is already abnormal and there may even be a lack of viable spermatozoa at the time of diagnosis. Therefore, the effect of cancer treatment on fertility is a potentially significant issue. Fertility preservation in these men has become essential and needs to be discussed prior to the start of cancer treatment. The only currently established fertility preservation method is the cryopreservation of sperm before therapy. For most patients seeking cryopreservation, the semen sample is collected via masturbation. If the patient is unable to ejaculate for any reason, other techniques such as vibratory stimulation and electroejaculation can be performed. In azoospermic or severely oligozoospermic patients, testicular sperm extraction at the time of the inguinal orchiectomy is a useful technique for obtaining spermatozoa before cytotoxic therapy. We herein present an overview of the current topics on fertility in TC patients, including the effects of surgery, chemotherapy, and radiation therapy. We also describe the strategy for fertility preservation in these patients. PMID:25812494

  18. The Zest for Patient Empowerment

    PubMed Central

    Thawani, Vijay

    2016-01-01

    Patient Empowerment (PE) can be considered as an active and self-determining role of patient than a passive recipient of health related services. It encourages the provider–patient relationship to blossom and helps in clearing patients’ doubts, confusion and fears to bring in clarity, relief and assurance. For the active involvement of the patient’s in own health management they need to be awakened, motivated, educated and enlightened to enable them to exercise their rights. Active patient involvement in the decision-making achieves favourable health outcome. In an empowerment based approach, the focus is not on defining a particular type of behaviour, but on how the behaviour is defined as a goal to be achieved by a particular individual. As a result of their empowerment process, the patients can better self-manage their illness and their lives. Thus empowerment of the patients will positively help medical uprising of the community by creating an educated, health aware, informed and health conscious mass. PMID:27504307

  19. Transfusion issues in cancer patients.

    PubMed

    Federici, Augusto B; Vanelli, Chiara; Arrigoni, Luisa

    2012-04-01

    Allogeneic blood transfusion (ABT) therapy plays a major role in the case of patients with cancer. Packed red blood cells (PRBC) are given for increased oxygen-carrying capacity, platelets concentrates (PC) and fresh frozen plasma (FFP) for the cessation and prevention of bleeding due to thrombocytopenia and other defects of hemostasis associated with neoplasia. All these blood components can induce complications and/or adverse reactions in cancer patients including transfusion-associated graft versus host disease (TA-GVHD), transfusion transmitted diseases, alloimmunization to blood cell antigens, pulmonary decompensation, immunomodulation. Therefore, specific modifications such as leukocyte-reduction and irradiation of the blood components to be transfused in cancer patients should be introduced to reduce the risk of these complications. Patients undergoing hematopoietic progenitor cell (HPC) transplantation are a unique group and present complex concerns related to transfusion, including major and minor ABO incompatibility and chimeric blood cells. Therefore, transfusion for patients undergoing treatment with cellular therapies requires careful blood component selection. The process of HPC infusion itself carries many risks including DMSO toxicity and hemolytic reactions. In all areas of transfusion therapy, new advances such as pathogen inactivation and synthetic alternatives to blood components should help to increase the safety and tolerance of transfusion in cancer patients. PMID:22682136

  20. Mutation in GM2A Leads to a Progressive Chorea-dementia Syndrome

    PubMed Central

    Salih, Mustafa A.; Seidahmed, Mohammed Z.; El Khashab, Heba Y.; Hamad, Muddathir H. A.; Bosley, Thomas M.; Burn, Sabrina; Myers, Angela; Landsverk, Megan L.; Crotwell, Patricia L.; Bilguvar, Kaya; Mane, Shrikant; Kruer, Michael C.

    2015-01-01

    Background The etiology of many cases of childhood-onset chorea remains undetermined, although advances in genomics are revealing both new disease-associated genes and variant phenotypes associated with known genes. Methods We report a Saudi family with a neurodegenerative course dominated by progressive chorea and dementia in whom we performed homozygosity mapping and whole exome sequencing. Results We identified a homozygous missense mutation in GM2A within a prominent block of homozygosity. This mutation is predicted to impair protein function. Discussion Although discovered more than two decades ago, to date, only five patients with this rare form of GM2 gangliosidosis have been reported. The phenotype of previously described GM2A patients has been typified by onset in infancy, profound hypotonia and impaired volitional movement, intractable seizures, hyperacusis, and a macular cherry red spot. Our findings expand the phenotypic spectrum of GM2A mutation-positive gangliosidosis to include generalized chorea without macular findings or hyperacusis and highlight how mutations in neurodegenerative disease genes may present in unexpected ways. PMID:26203402

  1. ETHICAL MODELS OF PHYSICIAN--PATIENT RELATIONSHIP REVISITED WITH REGARD TO PATIENT AUTONOMY, VALUES AND PATIENT EDUCATION.

    PubMed

    Borza, Liana Rada; Gavrilovici, Cristina; Stockman, René

    2015-01-01

    The present paper revisits the ethical models of patient--physician relationship from the perspective of patient autonomy and values. It seems that the four traditional models of physician--patient relationship proposed by Emanuel & Emanuel in 1992 closely link patient values and patient autonomy. On the other hand, their reinterpretation provided by Agarwal & Murinson twenty years later emphasizes the independent expression of values and autonomy in individual patients. Additionally, patient education has been assumed to join patient values and patient autonomy. Moreover, several authors have noted that, over the past few decades, patient autonomy has gradually replaced the paternalistic approach based on the premise that the physician knows what is best for the patient. Neither the paternalistic model of physician-patient relationship, nor the informative model is considered to be satisfactory, as the paternalistic model excludes patient values from decision making, while the informative model excludes physician values from decision making. However, the deliberative model of patient-physician interaction represents an adequate alternative to the two unsatisfactory approaches by promoting shared decision making between the physician and the patient. It has also been suggested that the deliberative model would be ideal for exercising patient autonomy in chronic care and that the ethical role of patient education would be to make the deliberative model applicable to chronic care. In this regard, studies have indicated that the use of decision support interventions might increase the deliberative capacity of chronic patients. PMID:26204658

  2. Regional anesthesia for the trauma patient: improving patient outcomes.

    PubMed

    Gadsden, Jeff; Warlick, Alicia

    2015-01-01

    Trauma is a significant health problem and a leading cause of death in all age groups. Pain related to trauma is frequently severe, but is often undertreated in the trauma population. Opioids are widely used to treat pain in injured patients but have a broad range of undesirable effects in a multitrauma patient such as neurologic and respiratory impairment and delirium. In contrast, regional analgesia confers excellent site-specific pain relief that is free from major side effects, reduces opioid requirement in trauma patients, and is safe and easy to perform. Specific populations that have shown benefits (including morbidity and mortality advantages) with regional analgesic techniques include those with fractured ribs, femur and hip fractures, and patients undergoing digital replantation. Acute compartment syndrome is a potentially devastating sequela of soft-tissue injury that complicates high-energy injuries such as proximal tibia fractures. The use of regional anesthesia in patients at risk for compartment syndrome is controversial; although the data is sparse, there is no evidence that peripheral nerve blocks delay the diagnosis, and these techniques may in fact facilitate the recognition of pathologic breakthrough pain. The benefits of regional analgesia are likely most influential when it is initiated as early as possible, and the performance of nerve blocks both in the emergency room and in the field has been shown to provide quality pain relief with an excellent safety profile. PMID:26316813

  3. Regional anesthesia for the trauma patient: improving patient outcomes

    PubMed Central

    Gadsden, Jeff; Warlick, Alicia

    2015-01-01

    Trauma is a significant health problem and a leading cause of death in all age groups. Pain related to trauma is frequently severe, but is often undertreated in the trauma population. Opioids are widely used to treat pain in injured patients but have a broad range of undesirable effects in a multitrauma patient such as neurologic and respiratory impairment and delirium. In contrast, regional analgesia confers excellent site-specific pain relief that is free from major side effects, reduces opioid requirement in trauma patients, and is safe and easy to perform. Specific populations that have shown benefits (including morbidity and mortality advantages) with regional analgesic techniques include those with fractured ribs, femur and hip fractures, and patients undergoing digital replantation. Acute compartment syndrome is a potentially devastating sequela of soft-tissue injury that complicates high-energy injuries such as proximal tibia fractures. The use of regional anesthesia in patients at risk for compartment syndrome is controversial; although the data is sparse, there is no evidence that peripheral nerve blocks delay the diagnosis, and these techniques may in fact facilitate the recognition of pathologic breakthrough pain. The benefits of regional analgesia are likely most influential when it is initiated as early as possible, and the performance of nerve blocks both in the emergency room and in the field has been shown to provide quality pain relief with an excellent safety profile. PMID:26316813

  4. Postoperative analgesia in elderly patients.

    PubMed

    Falzone, Elisabeth; Hoffmann, Clément; Keita, Hawa

    2013-02-01

    Elderly people represent the fastest-growing segment of our society and undergo surgery more frequently than other age groups. Effective postoperative analgesia is essential in these patients because inadequate pain control after surgery is associated with adverse outcomes in elderly patients. However, management of postoperative pain in older patients may be complicated by a number of factors, including a higher risk of age- and disease-related changes in physiology and disease-drug and drug-drug interactions. Physiological changes related to aging need to be carefully considered because aging is individualized and progressive. Assessment of pain management needs to include chronological age, biological age with regard to renal, liver and cardiac functions, and the individual profile of pathology and prescribed medications. In addition, ways in which pain should be assessed, particularly in patients with cognitive impairment, must be considered. Cognitively intact older patients can use most commonly used unidimensional pain scales such as the visual analogue scale (VAS), verbal rating scale (VRS), numeric rating scale (NRS) and facial pain scale (FPS). VRS and NRS are the most appropriate pain scales for the elderly. In older patients with mild to moderate cognitive impairment, the VRS is a better tool. For severe cognitively impaired older patients, behavioural scales validated in the postoperative context, such as Doloplus-2 or Algoplus, are appropriate. For postoperative pain treatment, most drugs (e.g. paracetamol, nonsteroidal anti-inflammatory drugs, nefopam, tramadol, codeine, morphine, local anaesthetics), techniques (e.g. intravenous morphine titration, subcutaneous morphine, intravenous or epidural patient-controlled analgesia, intrathecal morphine, peripheral nerve block) and strategies (e.g. anticipated intraoperative analgesia or multimodal analgesia) used for acute pain management can be used in older patients. However, in view of pharmacokinetic

  5. Antimicrobial Dose in Obese Patient

    PubMed Central

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

    2007-01-01

    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

  6. [Nutritional support in stroke patients].

    PubMed

    Burgos Peláez, Rosa; Segurola Gurrutxaga, Hegoi; Bretón Lesmes, Irene

    2014-01-01

    Stroke is a public health problem of the first order. In developed countries is one of the leading causes of death, along with cardiovascular disease and cancer. In addition, stroke is the leading cause of permanent disability in adulthood. Many of the patients who survive do so with significant sequelae that limit them in their activities of daily living. Most strokes (80-85%) are due to ischemia, while the rest are hemorrhagic. We have identified many modifiable risk factors, some with an important relationship with dietary factors or comorbidities in wich the diet has a significant impact. The incidence of malnutrition in stroke patients is not well known, but most likely impacts on patient prognosis. Furthermore, the nutritional status of patients admitted for stroke often deteriorates during hospitalization. It is necessary to perform a nutritional assessment of the patient in the early hours of admission, to determine both the nutritional status and the presence of dysphagia. Dysphagia, through alteration of the safety and efficacy of swallowing, is a complication that has an implication for nutritional support, and must be treated to prevent aspiration pneumonia, which is the leading cause of mortality in the stroke patient. Nutritional support should begin in the early hours. In patients with no or mild dysphagia that can be controlled by modifying the texture of the diet, they will start oral diet and oral nutritional supplementation will be used if the patient does not meet their nutritional requirements. There is no evidence to support the use of nutritional supplements routinely. Patients with severe dysphagia, or decreased level of consciousness will require enteral nutrition. Current evidence indicates that early nutrition should be initiated through a nasogastric tube, with any advantages of early feeding gastrostomy. Gastrostomy will be planned when the enteral nutrition support will be expected for long-term (4 weeks). Much evidence points to the

  7. 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, ...

  8. Depression and Anxiety in Migraine Patients

    MedlinePlus

    ... Depression and Anxiety in Migraine Patients Depression and Anxiety in Migraine Patients Todd A. Smitherman, PhD and ... if you experience these symptoms. Migraine, Depression, and Anxiety Many migraine patients suffer from symptoms of depression ...

  9. Perioperative care of the elderly patient.

    PubMed

    Palmer, Robert M

    2006-03-01

    Perioperative management is typically more complicated in older patients than in younger patients and requires more assessment and evaluation before surgery as well as precautionary steps after surgery to manage these high-risk patients. PMID:16570559

  10. Treating drug-dependent patients in hospitals.

    PubMed

    Skene, Loane; Keays, David; Gardner, Bruce

    2002-08-01

    Are hospital staff legally permitted to test drug-dependent patients for drugs or infectious disease without the patient's consent in order to treat the patient or to protect themselves or other patients? What should staff do with "suspicious" items in the patient's possession (drugs, credit cards in different names, firearms)? Can drug-dependent patients lawfully use illicit drugs in hospital? Who should supply and administer them? PMID:12242876

  11. Patient-Physician Web Messaging

    PubMed Central

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

    2005-01-01

    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 (Γ=0.557), and provider/staff satisfaction with computer skills (Γ=0.626) (Goodman-Kruskal Gamma [Γ] 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

  12. Managing diabetes in dialysis patients.

    PubMed

    O'Toole, Sam M; Fan, Stanley L; Yaqoob, M Magdi; Chowdhury, Tahseen A

    2012-03-01

    Burgeoning levels of diabetes are a major concern for dialysis services, as diabetes is now the most common cause of end-stage renal disease in most developed nations. With the rapid rise in diabetes prevalence in developing countries, the burden of end stage renal failure due to diabetes is also expected to rise in such countries. Diabetic patients on dialysis have a high burden of morbidity and mortality, particularly from cardiovascular disease, and a higher societal and economic cost compared to non-diabetic subjects on dialysis. Tight glycaemic and blood pressure control in diabetic patients has an important impact in reducing risk of progression to end stage renal disease. The evidence for improving glycaemic control in patients on dialysis having an impact on mortality or morbidity is sparse. Indeed, many factors make improving glycaemic control in patients on dialysis very challenging, including therapeutic difficulties with hypoglycaemic agents, monitoring difficulties, dialysis strategies that exacerbate hyperglycaemia or hypoglycaemia, and possibly a degree of therapeutic nihilism or inertia on the part of clinical diabetologists and nephrologists. Standard drug therapy for hyperglycaemia (eg, metformin) is clearly not possible in patients on dialysis. Thus, sulphonylureas and insulin have been the mainstay of treatment. Newer therapies for hyperglycaemia, such as gliptins and glucagon-like peptide-1 analogues have become available, but until recently, renal failure has precluded their use. Newer gliptins, however, are now licensed for use in 'severe renal failure', although they have yet to be trialled in dialysis patients. Diabetic patients on dialysis have special needs, as they have a much greater burden of complications (cardiac, retinal and foot). They may be best managed in a multidisciplinary diabetic-renal clinic setting, using the skills of diabetologists, nephrologists, clinical nurse specialists in nephrology and diabetes, along with

  13. Survival of Sami cancer patients

    PubMed Central

    Soininen, Leena; Pokhrel, Arun; Dyba, Tadek; Pukkala, Eero; Hakulinen, Timo

    2012-01-01

    Objectives The incidence of cancer among the indigenous Sami people of Northern Finland is lower than among the Finnish general population. The survival of Sami cancer patients is not known, and therefore it is the object of this study. Study design The cohort consisted of 2,091 Sami and 4,161 non-Sami who lived on 31 December 1978 in the two Sami municipalities of Inari and Utsjoki, which are located in Northern Finland and are 300–500 km away from the nearest central hospital. The survival experience of Sami and non-Sami cancer patients diagnosed in this cohort during 1979–2009 was compared with that of the Finnish patients outside the cohort. Methods The Sami and non-Sami cancer patients were matched to other Finnish cancer patients for gender, age and year of diagnosis and for the site of cancer. An additional matching was done for the stage at diagnosis. Cancer-specific survival analyses were made using the Kaplan–Meier method and Cox regression modelling. Results There were 204 Sami and 391 non-Sami cancer cases in the cohort, 20,181 matched controls without matching with stage, and 7,874 stage-matched controls. In the cancer-specific analysis without stage variable, the hazard ratio for Sami was 1.05 (95% confidence interval 0.85–1.30) and for non-Sami 1.02 (0.86–1.20), indicating no difference between the survival of those groups and other patients in Finland. Likewise, when the same was done by also matching the stage, there was no difference in cancer survival. Conclusion Long distances to medical care or Sami ethnicity have no influence on the cancer patient survival in Northern Finland. PMID:22765936

  14. Assessment of Patient Reported Outcomes (PROs) in Melanoma Patients

    PubMed Central

    Cormier, Janice N.; Askew, Robert L.

    2010-01-01

    SYNOPSIS Assessment of patient reported outcomes (PROs) has been shown to provide important information to assist with clinical decision-making. There has been significant progress in the field of PROs over the last two decades with the introduction of a variety of validated disease- and symptom-specific instruments. The Functional Assessment of Cancer Therapy-Melanoma (FACT-M) is a melanoma-specific module to accompany the FACT-General which has been validated to assess health-related quality of life (HRQOL) for patients with all stages of melanoma. Melanoma-specific health state utilities, which are essential for calculating quality adjusted life years and performing cost-effectiveness studies, have also been reported from a number of studies. Assessment of PROs should be incorporated into routine clinical practice to inform clinicians and researchers of the patient perspective for clinical decision-making and to evaluate the effects of psychosocial and medical interventions. PMID:21111967

  15. Thymectomy: Common Questions Patients Ask about Thymectomies

    MedlinePlus

    ... and to improve their lives through programs of patient services, public information, medical research, professional education, advocacy and patient care. This publication is intended to provide the ...

  16. Reducing patient suffering through compassionate connected care.

    PubMed

    Dempsey, Christina; Wojciechowski, Sharyl; McConville, Elizabeth; Drain, Maxwell

    2014-10-01

    Patient experience continues to play an increasingly critical role in quality outcomes and reimbursement. Nurse executives are tasked with helping direct-care nurses connect with patients to improve care experiences. Connecting with patients in compassionate ways to alleviate inherent patient suffering and prevent avoidable suffering is key to improving the patient experience. The Compassionate Connected Care framework identifies strategies for meeting the challenges of connecting with patients and reducing suffering. Methods integrate clinical, operational, cultural, and behavioral aspects of care to target patient needs based on condition. Caregivers learn to better express empathy and compassion to patients, and nurse leaders are better equipped to engage nurses at the bedside. PMID:25208270

  17. Bedside evaluation of dizzy patients.

    PubMed

    Huh, Young-Eun; Kim, Ji-Soo

    2013-10-01

    In recent decades there has been marked progress in the imaging and laboratory evaluation of dizzy patients. However, detailed history taking and comprehensive bedside neurotological evaluation remain crucial for a diagnosis of dizziness. Bedside neurotological evaluation should include examinations for ocular alignment, spontaneous and gaze-evoked nystagmus, the vestibulo-ocular reflex, saccades, smooth pursuit, and balance. In patients with acute spontaneous vertigo, negative head impulse test, direction-changing nystagmus, and skew deviation mostly indicate central vestibular disorders. In contrast, patients with unilateral peripheral deafferentation invariably have a positive head impulse test and mixed horizontal-torsional nystagmus beating away from the lesion side. Since suppression by visual fixation is the rule in peripheral nystagmus and is frequent even in central nystagmus, removal of visual fixation using Frenzel glasses is required for the proper evaluation of central as well as peripheral nystagmus. Head-shaking, cranial vibration, hyperventilation, pressure to the external auditory canal, and loud sounds may disclose underlying vestibular dysfunction by inducing nystagmus or modulating the spontaneous nystagmus. In patients with positional vertigo, the diagnosis can be made by determining patterns of the nystagmus induced during various positional maneuvers that include straight head hanging, the Dix-Hallpike maneuver, supine head roll, and head turning and bending while sitting. Abnormal smooth pursuit and saccades, and severe imbalance also indicate central pathologies. Physicians should be familiar with bedside neurotological examinations and be aware of the clinical implications of the findings when evaluating dizzy patients. PMID:24285961

  18. [Multifocal tuberculosis in immunocompetent patients].

    PubMed

    Rezgui, Amel; Fredj, Fatma Ben; Mzabi, Anis; Karmani, Monia; Laouani, Chadia

    2016-01-01

    Multifocal tuberculosis is defined as the presence of lesions affecting at least two extrapulmonary sites, with or without pulmonary involvement. This retrospective study of 10 cases aims to investigate the clinical and evolutionary characteristics of multifocal tuberculosis. It included 41 cases with tuberculosis collected between 1999 and 2013. Ten patients had multifocal tuberculosis (24%): 9 women and 1 man, the average age was 50 years (30-68 years). Our patients were correctly BCG vaccinated. The evaluation of immunodepression was negative in all patients. 7 cases had lymph node tuberculosis, 3 cases digestive tuberculosis, 2 cases pericardial tuberculosis, 2 cases osteoarticular tuberculosis, 1 case brain tuberculosis, 2 cases urinary tuberculosis, 4 cases urogenital tuberculosis, 1 case adrenal tuberculosis, 1 case cutaneous and 1 case muscle tuberculosis. All patients received anti-tuberculosis treatment for a mean duration of 10 months, with good evolution. Multifocal tuberculosis is difficult to diagnose. It can affect immunocompetent patients but often has good prognosis. Anti-tuberculosis therapy must be initiated as soon as possible to avoid sequelae. PMID:27583077

  19. Patients' satisfaction with facial prostheses.

    PubMed

    Wondergem, Marloes; Lieben, George; Bouman, Shirley; van den Brekel, Michiel W M; Lohuis, Peter J F M

    2016-05-01

    We assessed the "impact on wellbeing" and "satisfaction" of patients who had a facial prosthesis (of the ear, nose, or orbit) fitted in The Netherlands Cancer Institute. Patients had either an adhesive-retained or an implant-retained facial prosthesis between 1951 and 2011. We did a cross-sectional survey of 104 patients, then gave a questionnaire to the final study group of 71 (68%), a year or more later. All were satisfied with their prostheses (visual analogue scale (VAS): mean (SD) 8.1(1.5). The implant-retained group were the most satisfied (p=0.022), and the adhesive-retained group felt more self-conscious (p=0.013). Three-quarters of all patients said that the prosthesis was not painful and there were no problems with the way it functioned. A well-designed facial prosthesis has obvious benefits, but there were no appreciable differences between the two groups. Each patient must make a careful decision about which type of prosthesis to choose, taking into account the quality of their remaining tissue, the site of the defect, and their general health. PMID:26508540

  20. Syncope in Patients with Pacemakers

    PubMed Central

    Sutton, Richard

    2015-01-01

    Syncope in a pacemaker patient is a serious symptom but it is rarely due a pacemaker system malfunction. Syncope occurs in about 5 % of patients paced for atrioventricular (AV) block in 5 years, 18% in those paced for sinus node disease in 10 years, 20 % of those paced for carotid sinus syndrome in 5 years and 5–55 % of those older patients paced for vasovagal syncope in 2 years. The vastly different results in vasovagal syncope depend on the results of tilt testing, where those with negative tests approach results in pacing for AV block and those with a positive tilt test show no better results than with no pacemaker. The implication of tilt results is that a hypotensive tendency is clearly demonstrated by tilt positivity pointing to syncope recurrence with hypotension. This problem may be addressed by treatment with vasoconstrictor drugs in those who are suited or, more commonly, a reduction or cessation of hypotensive therapy in hypertensive patients. Other causes of syncope such as tachyarrhythmias are rare. The clinical approach to patients who report syncope is detailed. PMID:26835124

  1. Patient perspectives on radiation dose.

    PubMed

    Graff, Joyce

    2014-03-01

    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

  2. [COMMUNICATION WITH TERMINALLY ILL PATIENT].

    PubMed

    2014-12-01

    The communication is a essential therapeutic instrument in every process of relationship in the team patient-family, and mainly in the transmission of bad news. The communication is not just a simple transmission of information. It is a process whose goal is to enable the adaptation of the patient and family to their actual situation and where the "what", "how" and "how much do you want to know", are belonged to the own patient. Along this article, we will expose some thoughts that the team has to take into account when informing the patient. We are going to explain the SPIKES protocol, or its Spanish version EPICEE. 6-step protocol, based on those recommended by the experts to deliver bad news procedures. And finally we'll talk about the conspiracy of silence, one of the most common and difficult situations to handle in day to day due to paternalism by professionals and families, in which they prefer to hide the situation to the patient, thinking it's the best for him. PMID:26121886

  3. Aztreonam pharmacokinetics in burn patients.

    PubMed Central

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

    1991-01-01

    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

  4. Hypogonadism in male cancer patients.

    PubMed

    Burney, Basil O; Garcia, Jose M

    2012-09-01

    Prevalence of hypogonadism in men with cancer has been reported between 40% and 90%, which is significantly higher than in the general population. Hypogonadism is likely to affect the quality of life in these patients by contributing to non-specific symptoms, including decreased energy, anorexia, sarcopenia, weight loss, depression, insomnia, fatigue, weakness, and sexual dysfunction. Pathogenesis of hypogonadism in cancer patients is thought to be multi-factorial. Inflammation may play an important role, but leptin, opioids, ghrelin, and high-dose chemotherapy through different mechanisms have all been implicated as the cause. Hypogonadism is also associated with poor survival in cancer patients. Data looking into the treatment of hypogonadal male cancer patients with testosterone are limited. However, improvements in body weight, muscle strength, lean body mass, and quality of life have been shown in hypogonadal men with other chronic diseases on testosterone replacement therapy. Prospective and interventional trials are needed to test the efficacy and safety of testosterone treatment in improving quality of life of these patients. PMID:22528986

  5. Invasive Aspergillosis in Hematological Patients.

    PubMed

    Kimura, Shun-Ichi

    2016-01-01

    Invasive aspergillosis (IA) is still one of the leading causes of morbidity and mortality in hematological patients, although its outcome has been improving. Prolonged and profound neutropenia in patients receiving intensive chemotherapy for acute leukemia and stem cell transplantation is a major risk factor for IA. Allogeneic stem cell transplant recipients with graft-versus-host disease and corticosteroid use are also at high risk. Management in a protective environment with high efficiency particular air (HEPA) filter is generally recommended to prevent aspergillosis in patients with prolonged and profound neutropenia. Antifungal prophylaxis against Aspergillus species should be considered in patients with past history of aspergillosis or colonization of Aspergillus species, at facilities with high incidence of IA and those without a protective environment. Early diagnosis and prompt antifungal treatment is important to improve outcome. Imaging studies such as computed tomography and biomarkers such as galactomannan antigen and β-D-glucan are useful for early diagnosis. Empirical antifungal treatment based on persistent or recurrent fever during neutropenia despite broad-spectrum antibiotic therapy is generally recommended in high-risk patients. Alternatively, a preemptive treatment strategy has recently been proposed in the context of progress in the early diagnosis of IA based on the results of imaging studies and biomarkers. Voriconazole is recommended for initial therapy for IA. Liposomal amphotericin B is considered as alternative initial therapy. Combination antifungal therapy of echinocandin with voriconazole or liposomal amphotericin B could be a choice for refractory cases. PMID:27251320

  6. Gas Gangrene in Orthopaedic Patients

    PubMed Central

    Ying, Zhimin; Zhang, Min; Yan, Shigui; Zhu, Zhong

    2013-01-01

    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

  7. Creating a patient education tool.

    PubMed

    Stonecypher, Karen

    2009-10-01

    Developing a patient education tool based on low literacy levels, behavioral theories, role modeling, and The Joint Commission's standards was the primary objective of this project. The initial goal was merely to develop a population-appropriate patient education tool. This led to a process whereby significant knowledge was gained by all to enrich overall professional development. An interdisciplinary team developed a low-literacy, self-management book for patients who had suffered a stroke. Team experts were responsible for the development of specific subject matter. Editing addressed the message, readability, typeface and font size, and charts and illustrations. Collaboration with the National Stroke Association guided the didactic pedagogical content presented. A well-known cartoonist who was a U.S. military veteran was willing to work with the team to develop the illustrations. PMID:19831328

  8. [Drug rehabilitation in stroke patients].

    PubMed

    Skoromets, A A; Koval'chuk, V V

    2007-01-01

    An influence of different drugs on functional rehabilitation in post-stroke patients has been studied. We tested for efficacy medications with nootropic, metabolic and antioxidative activity as well as pathogenetic and symptomatic remedies for differential therapy of ischemic and haemorrhagic stroke (IS, HS). We analyzed 1920 stroke patients, including 1520 with IS and 400 with HS. The functional rehabilitation depending on different drugs was followed up 1 year after stroke using Barthel, Lindmark and Scandinavian scales for stroke. Moreover, we suggested a coefficient for calculating of drug efficacy. The results of the study revealed that the use of some traditional drugs was not well founded. The most efficient medications in the treatment of IS proved to be actovegin, instenon, berlition, rheopolyglucin and gliatilin. The beneficial effect on rehabilitation of patients with HS was found only for actovegin. PMID:18379517

  9. Patients as partners in innovation.

    PubMed

    Barnett, Sean J; Katz, Aviva

    2015-06-01

    As the culture of medical practice has evolved, so has the relationship between the physician and patient. This is decidedly true with regards to the introduction of innovative therapies, especially in the surgical arena. A critical challenge is identifying and defining innovative therapy. Is the proposed treatment an incremental change, a research proposal, or more commonly someplace in between? This gray area creates a transition zone commonly referred to as innovative therapy. Given the complexities of the current landscape of innovation, innovation therapy committees may provide a mechanism to help to guide both physicians and patients through such difficult topics as the process of informed consent, managing conflicts of interest, and how to evaluate the outcomes of innovative therapies. As surgical innovation remains critical to the advancement of care, it must occur in a transparent partnership with patients, under the eye of guiding entities, aimed at ultimately improving outcomes and care. PMID:25976152

  10. Counselling patients with hepatitis C.

    PubMed

    Zarski, J P; Leroy, V

    1999-01-01

    Hepatitis C virus (HCV) is usually but not exclusively transmitted by the parenteral route. Some precautions are recommended for infected patients as well as his/her close contacts and family members. The risk of sexual transmission and from household contacts is very low. Use of condoms is only recommended in cases of multiple partners and for those at high risk of transmission. Some personal objects should not be shared, i.e. razors, toothbrushes and nail clippers, but it is not necessary to avoid sharing eating utensils. Sexual partners may be tested for anti-HCV HCV-positive individuals should refrain from donating blood, organs and tissue. Clear and evidenced-based information should be provided to patients as to the means of prevention with special attention to individual risk groups such as IV drug abusers. The risk of HCV transmission after needlestick injury, although low, justifies universal precaution measurements for health-care workers. Nosocomial transmission has been described after medical procedures, especially haemodialysis and endoscopy. Thus, disinfection procedures as well as universal precautions are essential for all health-care workers. It is also important for HCV patients to inform health-care workers beforehand about their HCV status. Perinatal transmission is rare and is usually related to the degree of maternal viral load. Pregnancy is not contra-indicated in HCV. infected individuals and breast-feeding is allowed. Finally, HCV patients with active disease should be advised to refrain from alcohol intake, especially during antiviral therapy. After HCV infection it is necessary to consider not only diagnostic and therapeutic steps but also the risk of transmission in the patient's circle and consequences for the patient. PMID:10622576

  11. Alexithymia in chronic urticaria patients.

    PubMed

    Barbosa, Filipe; Freitas, João; Barbosa, Antonio

    2011-03-01

    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

  12. Cost trajectories for cancer patients

    PubMed Central

    Wodchis, W.P.; Arthurs, E.; Khan, A.I.; Gandhi, S.; MacKinnon, M.; Sussman, J.

    2016-01-01

    Background Health care spending is known to be highly skewed, with a small subset of the population consuming a disproportionate amount of health care resources. Patients with cancer are high-cost users because of high incremental health care costs for treatment and the growing prevalence of cancer. The objectives of the present study included characterizing cancer-patient trajectories by cost, and identifying the patient and health system characteristics associated with high health system costs after cancer treatment. Methods This retrospective cohort study identified Ontario adults newly diagnosed with cancer between 1 April 2009 and 30 September 2010. Costs of health care use before, during, and after cancer episodes were used to develop trajectories of care. Descriptive analyses examined differences between the trajectories in terms of clinical and health system characteristics, and a logistic regression approach identified predictors of being a high-cost user after a cancer episode. Results Ten trajectories were developed based on whether patients were high- or low-cost users before and after their cancer episode. The most common trajectory represented patients who were low-cost in the year before cancer, survived treatment, and continued to be low-cost in the year after cancer (31.4%); stage ii cancer of the male genital system was the most common diagnosis within that trajectory. Regression analyses identified increases in age and in multimorbidity and low continuity of care as the strongest predictors of high-cost status after cancer. Conclusions Findings highlight an opportunity to proactively identify patients who might transition to high-cost status after cancer treatment and to remediate that transition. PMID:26985150

  13. Candidemia in major burns patients.

    PubMed

    Renau Escrig, Ana I; Salavert, Miguel; Vivó, Carmen; Cantón, Emilia; Pérez Del Caz, M Dolores; Pemán, Javier

    2016-06-01

    Major burn patients have characteristics that make them especially susceptible to candidemia, but few studies focused on this have been published. The objectives were to evaluate the epidemiological, microbiological and clinical aspects of candidemia in major burn patients, determining factors associated with a poorer prognosis and mortality. We conducted a retrospective observational study of candidemia between 1996 and 2012 in major burn patients admitted to the La Fe University Hospital, Valencia, Spain. The study included 36 episodes of candidemia in the same number of patients, 55.6% men, mean age 37.33 years and low associated comorbidity. The incidence of candidemia varied between 0.26 and 6.09 episodes/1000 days stay in the different years studied. Candida albicans was the most common species (61.1%) followed by Candida parapsilosis (27.8%). Candidemia by C. krusei, C. glabrata or C. tropicalis were all identified after 2004. Central vascular catheter (CVC) was established as a potential source of candidemia in 36.1%, followed by skin and soft tissues of thermal injury (22.2%) and urinary tract (8.3%). Fluconazole was used in 19 patients (52.7%) and its in vitro resistance rate was 13.9%. The overall mortality was 47.2%, and mortality related to candidemia was 30.6%. Factors associated with increased mortality were those related to severe infection and shock. CVC was the most usual focus of candidemia. Fluconazole was the most common antifungal drug administered. The management of candidemia in major burn patients is still a challenge. PMID:26931414

  14. Hepatitis C in hemodialysis patients

    PubMed Central

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

    2015-01-01

    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)-α 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

  15. Seizure Treatment in Transplant Patients

    PubMed Central

    Shepard, Paul W.

    2013-01-01

    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

  16. Immunosuppression of the burned patient.

    PubMed

    Robins, E V

    1989-12-01

    The burn patient is highly susceptible to infection due to the loss of the skin as a barrier to microorganisms. Immune defenses are activated in response to the burn injury; however, some of these defenses are altered. Neutrophil chemotaxis is compromised by decreased perfusion caused by hypovolemia and the formation of microthrombi. Chemotaxis and phagocytosis are dependent on complement components that are reduced in a large burn wound. Neutrophil intracellular killing power is reduced as oxygen delivery to the wound is decreased. Humoral immunity is altered with the drop in IgG levels. Cell-mediated immunity is depressed and T cell lymphocyte counts are deceased. Suppressor T cells are generated. Specific sources of infection for the burn patient include the patient's own bacterial flora; hospital personnel; respiratory equipment; and catheters, both urinary and intravascular. The best control for burn wound infection is the closure of the wound by early excision and grafting. When lack of donor sites prohibits this surgical therapy, control centers on the environment and wound care techniques. The selection of wound topical antibiotics on the basis of visual inspection and surface culturing assists in the prevention of burn wound sepsis. When wound sepsis does occur, systemic antibiotics are instituted. Although burn wound sepsis is an obvious cause of death for the burn patient, it is not the primary cause. Increasing sophistication in fluid resuscitation and in intensive care therapy has resulted in patients living beyond the initial insult and the following few days. Burn patient mortality is now associated with a syndrome presenting clinically as sepsis but without any identifiable septic source.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2697225

  17. Infrared-Guided Patient Setup for Lung Cancer Patients

    SciTech Connect

    Lyatskaya, Yulia; James, Steven; Killoran, Joseph H.; Soto, Ricardo; Mamon, Harvey J.; Chin, Lee

    2008-07-15

    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.

  18. Managing complications in cirrhotic patients

    PubMed Central

    Angeli, Paolo; Cordoba, Juan; Farges, Oliver; Valla, Dominique

    2015-01-01

    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

  19. Ovarian stimulation in cancer patients.

    PubMed

    Cakmak, Hakan; Rosen, Mitchell P

    2013-05-01

    The patients referred for fertility preservation owing to a malignant disease do not represent the typical population of subfertile patients treated in IVF units. Cancer may affect multiple tissues throughout the body and can result in a variety of complications during controlled ovarian stimulation. Determination of the controlled ovarian stimulation protocol and gonadotropin dose for oocyte/embryo cryopreservation requires an individualized assessment. This review highlights the new protocols that are emerging to reduce time constraints and emphasizes management considerations to decrease complications. PMID:23635348

  20. The earliest gamma unit patients.

    PubMed

    Ganz, Jeremy C

    2014-01-01

    The inventors were very excited and drove the first patient from Stockholm over 100 km for the first treatment. The treatment was a technical success. The new machine was transported to Sophiahemmet (a private Stockholm hospital) and installed. A further eight patients were treated and assessed. At the start, there was no computerized treatment planning program, but this was soon developed and named KULA after the Swedish word for a sphere, since the actual treatment unit was spherical. The term Gamma Knife was first used later by the Pittsburgh group. PMID:25376571