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6. Repetitive transcranial magnetic stimulation in patients with late life depression influences phenylalanine metabolism

Author

Leblhuber F, Steiner K, Gostner Jm, and Fuchs D

Subjects
late life depression, neopterin, phenylalanine hydroxylase, phenylalanine to tyrosineratio, transcranial magnetic stimulation, tryptophan metabolism, Crystallography, QD901-999
Abstract

Repetitive transcranial magnetic stimulation (rTMS) is used to treat different neuropsychiatric conditions like Parkinson’s disease, essential tremor, stroke, cognitive decline, dementia and depression. rTMS may exert its therapeutic effects by influencing the biochemistry of neurotransmitters. In this exploratory study, safety symptom improvement and changes in the availability of neurotransmitter precursor amino acids were studied following prefrontal cortex (PFC) stimulation using repetitive transcranial stimulation with TheraCell apparatus R (Guth Meditec, Salach, Germany) as an additional treatment in ten patients with late life depression. Treatment was well tolerated with no serious adverse effects being observed. rTMS induced a significant improvement in the symptoms of depression and a significant decrease in the HAMD-7 (p

Published
2018
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13. Dental Health and Mortality in People With End-Stage Kidney Disease Treated With Hemodialysis: A Multinational Cohort Study

Author

Raña, S., Serrano, M., Claros, S., Arias, M., Petracci, L., Arana, M., De Rosa, P., Gutierrez, A., Simon, M., Vergara, V., Tosi, M., Cernadas, M., Vilamajó, I., Gravac, D., Paulón, M., Penayo, L., Carrizo, G., Ghiani, M., Perez, G., Da Cruz, O., Galarce, D., Gravielle, M., Vescovo, E., Paparone, R., Mato Mira, C., Mojico, E., Hermida, O., Florio, D., Yucoswky, M., Labonia, W., Rubio, D., Di Napoli, G., Fernandez, A., Altman, H., Rodriguez, J., Serrano, S., Valle, G., Lobos, M., Acosta, V., Corpacci, G., Jofre, M., Gianoni, L., Chiesura, G., Capdevila, M., Montenegro, J., Bequi, J., Dayer, J., Gómez, A., Calderón, C., Abrego, E., Cechín, C., García, J., Corral, J., Natiello, M., Coronel, A., Muñiz, M., Muñiz, V., Bonelli, A., Sanchez, F., Maestre, S., Olivera, S., Camargo, M., Avalos, V., Geandet, E., Canteli, M., Escobar, A., Sena, E., Tirado, S., Peñalba, A., Neme, G., Cisneros, M., Oliszewski, R., Nascar, V., Daud, M., Mansilla, S., Paredes Álvarez, A., Gamín, L., Arijón, M., Coombes, M., Zapata, M., Boriceanu, C., Frantzen-Trendel, S., Albert, K., Csaszar, I., Kiss, E., Kosa, D., Orosz, A., Redl, J., Kovacs, L., Varga, E., Szabo, M., Magyar, K., Kriza, G., Zajko, E., Bereczki, A., Csikos, J., Kuti, A., Mike, A., Steiner, K., Nemeth, E., Tolnai, K., Toth, A., Vinczene, J., Szummer, Sz., Tanyi, E., Toth, R., Szilvia, M., Dambrosio, N., Paparella, G., Sambati, M., Donatelli, C., Pedone, F., Cagnazzo, V.A., Antinoro, R., Torsello, F., Saturno, C., Giannoccaro, G., Maldera, S., Boccia, E., Mantuano, M., Di Toro Mammarella, R., Meconizzi, M., Steri, P.F., Riccardi, C., Flammini, A., Moscardelli, L., Murgo, M., San Filippo, N., Pagano, S., Marino, G., Montalto, G., Cantarella, S., Salamone, B., Randazzo, G., Rallo, D., Maniscalco, A., Fici, M., Lupo, A., Pellegrino, P., Fichera, R., D’Angelo, A., Falsitta, N., Bochenska-Nowacka, E., Jaroszynski, A., Drabik, J., Birecka, M., Daniewska, D., Drobisz, M., Doskocz, K., Wyrwicz, G., Inchaustegui, L., Outerelo, C., Sousa Mendes, D., Mendes, A., Lopes, J., Barbas, J., Madeira, C., Fortes, A., Vizinho, R., Cortesão, A., Almeida, E., Bernat, A., De la Torre, B., Lopez, A., Martín, J., Cuesta, G., Rodriguez, R.M., Ros, F., Garcia, M., Orero, E., Ros, E., Caetano, A., MacGregor, K., Santos, M., Silva Pinheiro, S., Martins, L., Leitão, D., Izidoro, C., Bava, G., Bora, A., Gorena, H., Calderón, T., Dupuy, R., Alonso, N., Siciliano, V., Nagy, K., Bajusz, Ö., Pinke, I., Decsi, G., Gyergyoi, L., Jobba, Zs., Zalai, Zs., Zsedenyi, Á., Kiss, G., Pinter, M., Kereszturi, M., Petruzzi, M., De Benedittis, M., Szkutnik, J., Sieczkarek, J., Capelo, A., Garcia Gallart, M., Mendieta, C., Palmer, Suetonia C., Ruospo, Marinella, Wong, Germaine, Craig, Jonathan C., Petruzzi, Massimo, De Benedittis, Michele, Ford, Pauline, Johnson, David W., Tonelli, Marcello, Natale, Patrizia, Saglimbene, Valeria, Pellegrini, Fabio, Celia, Eduardo, Gelfman, Ruben, Leal, Miguel R., Torok, Marietta, Stroumza, Paul, Bednarek-Skublewska, Anna, Dulawa, Jan, Frantzen, Luc, Ferrari, Juan Nin, del Castillo, Domingo, Bernat, Amparo G., Hegbrant, Jorgen, Wollheim, Charlotta, Gargano, Letizia, Bots, Casper P., and Strippoli, Giovanni F.M.

Published
2015
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15. We are much more than books

Author

Harriss, E, Smith, C, Phillips, D, White, G, Steiner, K, Henry, M, Thurley, N, and Roberts, N

Abstract

We are much more than books. We are experts in systematic reviews, literature searches, training, research question formulation, databases, Boolean logic, and reference management. We are trainers, searchers, authors, and problem solvers. We help students and staff in the university and in the OUH NHS trust.

Published
2022

17. Quantitative suspecptibility mapping reveals alterations of denate nuclei in common types of ataxias

Author

Deistung, A., Jäschke, D., Münchau, A., Minnerop, Martina, Göricke, S. L., Reichenbach, J. R., Timmann, D., Draganova, R., Pfaffenrot, V., Hulst, T., Steiner, K. M., Thieme, A., Giordano, I. A., Klockgether, T., and Tunc, S.

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, nervous system, ddc:610
Abstract

The cerebellar nuclei are a brain region with high iron content. Surprisingly, little is known about iron content in the cerebellar nuclei and its possible contribution to pathology in cerebellar ataxias, with the only exception of Friedreich’s ataxia. In the present exploratory cross-sectional study, quantitative susceptibility mapping was used to investigate volume, iron concentration and total iron content of the dentate nuclei in common types of hereditary and non-hereditary degenerative ataxias. Seventy-nine patients with spinocerebellar ataxias of types 1, 2, 3 and 6; 15 patients with Friedreich’s ataxia; 18 patients with multiple system atrophy, cerebellar type and 111 healthy controls were also included. All underwent 3 T MRI and clinical assessments. For each specific ataxia subtype, voxel-based and volumes-of-interest-based group analyses were performed in comparison with a corresponding age- and sex-matched control group, both for volume, magnetic susceptiblity (indicating iron concentration) and susceptibility mass (indicating total iron content) of the dentate nuclei. Spinocerebellar ataxia of type 1 and multiple system atrophy, cerebellar type patients showed higher susceptibilities in large parts of the dentate nucleus but unaltered susceptibility masses compared with controls. Friedreich’s ataxia patients and, only on a trend level, spinocerebellar ataxia of type 2 patients showed higher susceptibilities in more circumscribed parts of the dentate. In contrast, spinocerebellar ataxia of type 6 patients revealed lower susceptibilities and susceptibility masses compared with controls throughout the dentate nucleus. Spinocerebellar ataxia of type 3 patients showed no significant changes in susceptibility and susceptibility mass. Lower volume of the dentate nuclei was found to varying degrees in all ataxia types. It was most pronounced in spinocerebellar ataxia of type 6 patients and least prominent in spinocerebellar ataxia of type 3 patients. The findings show that alterations in susceptibility revealed by quantitative susceptibility mapping are common in the dentate nuclei in different types of cerebellar ataxias. The most striking changes in susceptibility were found in spinocerebellar ataxia of type 1, multiple system atrophy, cerebellar type and spinocerebellar ataxia of type 6. Because iron content is known to be high in glial cells but not in neurons of the cerebellar nuclei, the higher susceptibility in spinocerebellar ataxia of type 1 and multiple system atrophy, cerebellar type may be explained by a reduction of neurons (increase in iron concentration) and/or an increase in iron-rich glial cells, e.g. microgliosis. Hypomyelination also leads to higher susceptibility and could also contribute. The lower susceptibility in SCA6 suggests a loss of iron-rich glial cells. Quantitative susceptibility maps warrant future studies of iron content and iron-rich cells in ataxias to gain a more comprehensive understanding of the pathogenesis of these diseases.

Published
2022

29. Poster abstracts

Author

Marshall, N. S., Almqvist, C., Grunstein, R. R., Marks, G. B., Nixon, G. M., Wawruszak, M., Verginis, N., Horne, R. S. C., Davey, M. J., Blunden, S. L., Chervin, R. D., Ng, M. L., O’Driscoll, D. M., Yang, J. S. C., Noa, A. M., Lushington, K., Camfferman, D., Gold, M., Kennedy, D., Galland, B. C., Taylor, B. J., Tripp, E. G., Phillips, A. M., Lrichardson, H., Verbeek, M., Parslow, P., Scott, S., Walker, A. M., Harding, R., Richards, H., Lack, L., Gradisar, M., Harris, J., Vu, T., Mitchell, P. I., Toth, K. A., Mcculloch, B. J., Campbell, A., Signal, T. L., O’Keeffe, K., Kanbayashi, T., Kondo, H., Satoh, S., Takemura, T., Kaneko, Y., Kanayama, H., Abe, M., Nishino, S., Ishikawa, H., Shimizu, T., Stadler, D., Catcheside, P., George, K., Thompson, C., Ryan, M., Mcevoy, R. D., Wilkinson, V., Nicholas, C., Worsnop, C., Jordan, A., Malhotra, A., Steiner, K., White, D., Trinder, J., Hellgren, J., Lee, Y., O’Brien, D., Yee, B., Rimmer, J., Grunstein, R., Hilditch, C. J., Catcheside, P. G., Rischmueller, M., Kirkness, J. P., Schneider, H., Patil, S. P., Mcginley, B. M., Smith, P. L., Schwartz, A. R., Maddison, K. J., Walsh, J. H., Philippe, D. L., Platt, P. R., Hillman, D. R., Eastwood, P. R., Yeo, A., Thomson, K., Melehan, K. L., Bartlett, D. J., Wong, K. K., Car, G., Feenstra, J. F. E., Eckert, B., Rixon, K., Hukins, C., Crummy, F., Kossmann, T., Cameron, P., Naughton, M. T., Larby, J. R., Curtin, D., Semple, K., Douglas, J., Lee, Y. H., Edwards, N., Sullivan, C. E., Lehman, S., Antic, N. A., Mcevoy, D., Mukherjee, S., Fedson, A., Palmer, L. J., Love, G., Singh, B., James, A., Cullen, S. C., Mcardle, N., Hillman, D., Clarke, P. F., Van Eps, C., Hawley, C., Lee, R. W., Chan, A. S., Cistulli, P. A., Abdul Latif, H., Stick, S., Maul, J., Wilson, A., Suresh, S., James, J., Byrne, S., Doull, I., Evans, H., Parsley, C. L., Williams, G., Dakin, C., Harris, M., Cooper, D. M., Heussler, H., Chan, E. Y.-T., Hyde, M. L., Yuill, M., Harris, M. A., Schibler, A., Wilson, S., Cooper, D., Maclean, J. E., Fitzsimons, D., Waters, K., Fitzgerald, D., Coussens, S., Berryman, M., Parsons, D., Saint, D., Pamula, Y., Martin, A. J., Abbot, D., Piper, A. J., Wang, D., Yee, B. J., Willson, G. N., Flunt, D., Bassin, D., Bateman, P., Ratnavadivel, R., Lester, S., Huang, Q. R., He, H. X., Chow, C. M., Jones, A. C., Visvalingam, V. V., Lui, P., Buchanan, P., Duce, B. L., Bliss, R. A., Bruck, D., Afaghi, A., O’Connor, H., Smith, S. S., Kilby, S., Jorgensen, G., Douglas, J. A., Johns, M. W., Tucker, A. J., Chapman, R. J., Michael, N. J., Beale, C. A., Stephens, M. N., Ferguson, S. A., Lamond, N., Jay, S. M., Dorrian, J., Jones, C. B., Roach, G. D., Dawson, D., Jackson, M. L., Howard, M. E., Kennedy, G., Swann, P., Pierce, R. J., Loughran, S. P., Wood, A. W., Croft, R. J., Barton, J. M., Thompson, B., Stough, C., Kandelaars, K., Warman, G. R., Bolton, C. A., Fernando, III, A. T., Cheeseman, J. F., Inglis, C., Huang, H.-C. C., Wlee, R., Richards, D., Turton, A., Copland, J., Ho, M., Rochford, P. D., Brazzale, D. J., Zubrinich, C., Roebuck, T. J., Toman, P., Ho, S., Szollosi, I., Naughton, M., Ruehland, W., Churchward, T., Ruehland, W. R., Churchward, T. J., Barnes, M., Lakey, T., Denotti, A. L., Dungan, G. C., Wong, K. K. H., Gilholme, J. W., Cunnington, D., Cherry, G., Teichtahl, H., Mietus, J. E., Goldberger, A. L., Thomas, R. J., Linklater, S., Martin, J., Galilogadr, S., Mihai, R., Gulliver, T., Wales, P., Salvini, A., Whitehead, B., Laybutt, N., Latham-Smith, F., Shine, N. P., Coates, H. L., Lannigan, F. J., Ng, A. T., Darendeliler, M. A., Zeng, B., Ng, A., Darendeliler, A., Cistulli, P., Qian, J., Hanssen, K., Schnider, H., Lewis, R. H., De Fazio, D., Pierce, R., Pretto, J., Mcdonald, C., Howard, M., Baulk, S. D., Biggs, S. N., Van Den Heuvel, C. J., Reid, K., Vakulin, A., Anderson, R., Banks, S., Davies, A. N., Williams, A. D., Almond, J., Beard, D., Peisker, C., Ball, M., Taylor, A., Wright, H., Clark, R., Hensley, M., Rowland, S., Windler, S., Kennedy, G. A., Gullo, M., Clarke, C., Gain, K., Murphy, M., Rebus, C., Saunders, K., Imazu, M., Morgan, H., Kwan, M., Nicholls, G., Tolson, J., Worsnop, C. J., Navin, C., Baker, G., and Van Der Touw, T.

Published
2006
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30. Phenobarbital, Midazolam Pharmacokinetics, Effectiveness, and Drug-Drug Interaction in Asphyxiated Neonates Undergoing Therapeutic Hypothermia

Author

Favie, L.M.A., Groenendaal, F., Broek, M.P.H. van den, Rademaker, C.M.A., Haan, T.R. de, Straaten, H.L.M. van, Dijk, P.H., Heijst, A. van, Simons, S.H.P., Dijkman, K.P., Rijken, M., Zonnenberg, I.A., Cools, F., Zecic, A., Lee, J.H. van der, Nuytemans, D.H.G.M., Bel, F. van, Egberts, T.C.G., Huitema, A.D.R., Brouwer, M.J., Mulder-de Tollenaer, S.M., Jebbink-Akkerman, L.J.M.G., Liem, D., Steiner, K., Dudink, J., Jonge, R.C.J. de, Bos, A.A., Sonnaert, M., Camfferman, F.A., PharmaCool Study Grp, Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Clinical sciences, Growth and Development, Neonatology, Pediatrics, Pediatric surgery, Amsterdam Reproduction & Development (AR&D), AGEM - Endocrinology, metabolism and nutrition, AGEM - Digestive immunity, AII - Inflammatory diseases, General Paediatrics, AGEM - Inborn errors of metabolism, APH - Methodology, APH - Quality of Care, and ARD - Amsterdam Reproduction and Development

Subjects
Male, genetic structures, medicine.medical_treatment, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], INFANTS, BRAIN-INJURY, Pediatrics, 0302 clinical medicine, Hypothermia, Induced, Medicine and Health Sciences, Medicine, Drug Interactions, heterocyclic compounds, Prospective Studies, 030212 general & internal medicine, Asphyxia Neonatorum, Maintenance dose, NEWBORNS, INDUCTION, Perinatology, and Child Health, midazolam, Anesthesia, Phenobarbital, Hypoxia-Ischemia, Brain, Practice Guidelines as Topic, Anticonvulsants, Drug Therapy, Combination, Female, medicine.symptom, pharmacokinetics, psychological phenomena and processes, medicine.drug, Metabolic Clearance Rate, Sedation, Midazolam, Hypoxic-ischaemic encephalopathy, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Pharmacokinetics, 030225 pediatrics, Journal Article, Humans, Pediatrics, Perinatology, and Child Health, Original Paper, DISPOSITION, business.industry, Infant, Newborn, CYTOCHROME-P450, Neonates, SEDATION, Hypothermia, PHARMACODYNAMICS, EFFICACY, hypoxic-ischaemic encephalopathy, neonates, Anticonvulsant, Pharmacodynamics, Pediatrics, Perinatology and Child Health, SEIZURES, business, Developmental Biology
Abstract

Background: Phenobarbital and midazolam are commonly used drugs in (near-)term neonates treated with therapeutic hypothermia for hypoxic-ischaemic encephalopathy, for sedation, and/or as anti-epileptic drug. Phenobarbital is an inducer of cytochrome P450 (CYP) 3A, while midazolam is a CYP3A substrate. Therefore, co-treatment with phenobarbital might impact midazolam clearance. Objectives: To assess pharmacokinetics and clinical anti-epileptic effectiveness of phenobarbital and midazolam in asphyxiated neonates and to develop dosing guidelines. Methods: Data were collected in the prospective multicentre PharmaCool study. In the present study, neonates treated with therapeutic hypothermia and receiving midazolam and/or phenobarbital were included. Plasma concentrations of phenobarbital and midazolam including its metabolites were determined in blood samples drawn on days 2–5 after birth. Pharmacokinetic analyses were performed using non-linear mixed effects modelling; clinical effectiveness was defined as no use of additional anti-epileptic drugs. Results: Data were available from 113 (phenobarbital) and 118 (midazolam) neonates; 68 were treated with both medications. Only clearance of 1-hydroxy midazolam was influenced by hypothermia. Phenobarbital co-administration increased midazolam clearance by a factor 2.3 (95% CI 1.9–2.9, p < 0.05). Anticonvulsant effectiveness was 65.5% for phenobarbital and 37.1% for add-on midazolam. Conclusions: Therapeutic hypothermia does not influence clearance of phenobarbital or midazolam in (near-)term neonates with hypoxic-ischaemic encephalopathy. A phenobarbital dose of 30 mg/kg is advised to reach therapeutic concentrations. Phenobarbital co-administration significantly increased midazolam clearance. Should phenobarbital be substituted by non-CYP3A inducers as first-line anticonvulsant, a 50% lower midazolam maintenance dose might be appropriate to avoid excessive exposure during the first days after birth.

Published
2019

43. Computational Analysis of Nonuniform Expansion in Polyurethane Foams

Author

Niedziela, D., Ireka, I.E., Steiner, K., and Publica

Subjects
lcsh:QD241-441, Condensed Matter::Soft Condensed Matter, lcsh:Organic chemistry, nonuniform expansion, reaction injection molding, polyurethane foams, chemorheology, foam fraction distribution, finite-volume method, Article
Abstract

This paper computationally investigates heterogeneity in the distribution of foam fraction in chemically expanding blown polyurethane foam. The experimentally observed disparity in the volumes of expanded foam when an equal mass of the foaming mixture was injected into tubes of different dimensions motivated this study. To understand this phenomenon, attributed to local variations in the thermal and rheological properties of the expanding system, we explore available data from free-rise foam-expansion experiments in different geometries. Inspired by the mathematical framework for the microstructure modelling of bubble growth in viscous liquids, we study the reacting mixture as a continuum and formulate appropriate mathematical models that account for spatial inhomogeneity in the foam-expansion process. The nonlinear coupled system of partial differential equations governing flow was numerically solved using finite-volume techniques, and the associated results are presented and discussed with graphical illustrations. The proximity of the foaming-mixture core to the external environment and the thickness of a thermal-diffusion layer formed near the bounding geometry was seen to influence the distribution of the foam fraction. Our simulations showed an average spatial variation of about 1.1% in the distribution of solid foam fraction from the walls to the core, as verified with data from &mu, CT scan analysis of the expanded foam. This also reflects the distribution of void fraction in the foam matrix. The models were validated with experimental data, and our results favourably compared with the experiment observations.

Published
2019

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