152 results on '"P Kurtzhals"'
Search Results
2. Epimorphisms between finitely generated algebras
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Carai, Luca, Kurtzhals, Miriam, and Moraschini, Tommaso
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Mathematics - Logic ,18A20, 08C15, 08B10, 08B26, 06D20 - Abstract
A quasivariety has the weak ES property when the epimorphisms between its finitely generated members are surjective. A characterization of quasivarieties with the weak ES property is obtained and a method for detecting failures of this property in quasivarieties with a near unanimity term and in congruence permutable varieties is given. It is also shown that under reasonable assumptions the weak ES property implies arithmeticity. In particular, every filtral variety with the weak ES property is a discriminator variety.
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- 2024
3. From Global Domains to Physical Activity Environments: Development and Initial Validation of a Questionnaire-Based Physical Literacy Measure Designed for Large-Scale Population Surveys
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Peter Elsborg, Paulina S. Melby, Mette Kurtzhals, Helene Kirkegaard, Johannes Carl, Steffen Rask, Peter Bentsen, and Glen Nielsen
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This study aimed to develop and test MyPL, a questionnaire that measures self-reported physical literacy (PL) among children and adolescents. First, the item pool was developed and adapted, and face validity was tested with cognitive interviewing. Then, factor structures were identified through multidimensional scaling and exploratory factor analyses in a sample of 951 children (ages 7-13). Then, the identified models were tested using confirmatory factor analyses (CFA) within a sample of 2861 children (ages 7-12) and a sample of 1518 children (ages 13-15). Finally, measurement invariance and predictive validity were investigated. CFA showed that the identified physical activity (PA) environment-based models fitted better with the data than the domain-derived model. Reliability analyses showed that the internal consistency of the total PL scale was good and that, the reliability of the identified scales, except the cognitive scale, of the two models based on PA environments was satisfactory. Additionally, MyPL also showed measurement invariance across gender. This study suggests that the type of PA and the environment in which PA occur is important to consider when designing PL measurement tools. This study indicated that MyPL can be used to measure children and young people's PL in large surveys.
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- 2024
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4. Chain splitting of insulin: an underlying mechanism of insulin resistance?
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Cramer, Christian N., Hubálek, František, Brand, Christian Lehn, Helleberg, Hans, Kurtzhals, Peter, and Sturis, Jeppe
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- 2024
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5. An Assessment of Environmental Literacy, Behaviors, Attitudes and Lifestyle Factors of College Students
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Dawn Bloyd Null, Kristiana Feeser, and Geory Kurtzhals
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Objective: Evaluate associations between environmental literacy, attitudes, sustainability behaviors, health, and lifestyle factors among undergraduates. Participants: Convenience sample of 345 students at a mid-sized, rural university completed the survey fall 2019. Methods Descriptive statistics, correlations, and exploratory factor analysis were used to evaluate data. Results: Overall, though participants exhibited a lack of environmental knowledge (average score five of ten), they possessed pro-health and pro-environment attitudes and were likely to engage in corresponding behaviors (e.g. recycling, waste reduction, etc.). Principal axis factor analysis identified five underlying factors: liberal/progressive views, individual eco-friendly practices, personal health, healthy lifestyle, and waste reduction. Conclusion: Correlational analyses indicated students who value health and engage in healthier behaviors also value the environment. While most agreed environmental sustainability is important, recycling behaviors and sustainability knowledge were mediocre. Understanding underlying factors such as environmental attitudes and sustainability-related behaviors can drive intervention strategies to move students to action.
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- 2023
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6. Detection and quantification of Plasmodium falciparum in human blood by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry: a proof of concept study
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Stauning, Marius Ahm, Jensen, Christian Salgård, Staalsøe, Trine, and Kurtzhals, Jørgen A. L.
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- 2023
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7. Attributable Patient Cost of Antimicrobial Resistance: A Prospective Parallel Cohort Study in Two Public Teaching Hospitals in Ghana
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Otieku, Evans, Fenny, Ama Pokuaa, Labi, Appiah-Korang, Ofori, Alex Owusu, Kurtzhals, Joergen Anders Lindholm, and Enemark, Ulrika
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- 2023
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8. Derivatization with fatty acids in peptide and protein drug discovery
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Kurtzhals, Peter, Østergaard, Søren, Nishimura, Erica, and Kjeldsen, Thomas
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- 2023
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9. Exploring a parent-focused physical literacy intervention for early childhood: a pragmatic controlled trial of the PLAYshop
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Lane, Cassandra, Naylor, Patti-Jean, Predy, Madison, Kurtzhals, Mette, Rhodes, Ryan E., Morton, Kayla, Hunter, Stephen, and Carson, Valerie
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- 2022
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10. Digital health competencies in medical school education: a scoping review and Delphi method study
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Khurana, Mark P., Raaschou-Pedersen, Daniel E., Kurtzhals, Jørgen, Bardram, Jakob E., Ostrowski, Sisse R., and Bundgaard, Johan S.
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- 2022
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11. Correction to: Malaria causes long-term effects on markers of iron status in children: a critical assessment of existing clinical and epidemiological tools
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Castberg, Filip C., Sarbah, Edem W., Koram, Kwadwo A., Opoku, Nicholas, Ofori, Michael F., Styrishave, Bjarne, Hviid, Lars, and Kurtzhals, Jørgen A. L.
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- 2022
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12. Translation and validation of the Canadian assessment of physical literacy-2 in a Danish sample
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Elsborg, Peter, Melby, Paulina S., Kurtzhals, Mette, Tremblay, Mark S., Nielsen, Glen, and Bentsen, Peter
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- 2021
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13. Insulin at 100: still central in protein-based therapy for chronic disease
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Kurtzhals, Peter, von Scholten, Bernt Johan, Kreiner, Frederik Flindt, and Gough, Stephen Charles Langford
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- 2021
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14. High rates of multi-drug resistant gram-negative organisms associated with surgical site infections in a teaching hospital in Ghana
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Bediako-Bowan, Antoinette A. A., Kurtzhals, Jørgen A. L., Mølbak, Kåre, Labi, Appiah-Korang, Owusu, Enid, and Newman, Mercy J.
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- 2020
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15. In vitro selection for adhesion of Plasmodium falciparum-infected erythrocytes to ABO antigens does not affect PfEMP1 and RIFIN expression
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van der Puije, William, Wang, Christian W., Sudharson, Srinidhi, Hempel, Casper, Olsen, Rebecca W., Dalgaard, Nanna, Ofori, Michael F., Hviid, Lars, Kurtzhals, Jørgen A. L., and Staalsoe, Trine
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- 2020
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16. The impact of restricted gestational weight gain by dietary intervention on fetal growth in women with gestational diabetes mellitus
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Kurtzhals, Lise L., Nørgaard, Sidse K., Secher, Anna L., Nichum, Vibeke L., Ronneby, Helle, Tabor, Ann, McIntyre, H. David, Damm, Peter, and Mathiesen, Elisabeth Reinhardt
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- 2018
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17. Antibiotic use in surgical units of selected hospitals in Ghana: a multi-centre point prevalence survey
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Bediako-Bowan, Antoinette A. A., Owusu, Enid, Labi, Appiah-Korang, Obeng-Nkrumah, Noah, Sunkwa-Mills, Gifty, Bjerrum, Stephanie, Opintan, Japheth Awuletey, Bannerman, Cynthia, Mølbak, Kåre, Kurtzhals, Jørgen Anders Lindholm, and Newman, Mercy Jemima
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- 2019
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18. Malaria causes long-term effects on markers of iron status in children: a critical assessment of existing clinical and epidemiological tools
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Castberg, Filip C., Sarbah, Edem W., Koram, Kwadwo A., Opoku, Nicholas, Ofori, Michael F., Styrishave, Bjarne, Hviid, Lars, and Kurtzhals, Jørgen A. L.
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- 2018
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19. Antibiotic prescribing in paediatric inpatients in Ghana: a multi-centre point prevalence survey
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Labi, Appiah-Korang, Obeng-Nkrumah, Noah, Sunkwa-Mills, Gifty, Bediako-Bowan, Antoinette, Akufo, Christiana, Bjerrum, Stephanie, Owusu, Enid, Enweronu-Laryea, Christabel, Opintan, Japheth Awuletey, Kurtzhals, Jorgen Anders Lindholm, and Newman, Mercy Jemima
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- 2018
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20. The Human Insulin Thermal Solution project—a private sector initiative to address the thermostability of insulin
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Rasmussen, Mats, Hach, Morten, Iwersen, Jørgen, Anil, Gayathri, Rosborg, Henrik, Larsen, Jens, Hoffmann, Lise Camilla, and Kurtzhals, Peter
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- 2024
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21. Progressive disseminated histoplasmosis in the HIV population in Europe in the HAART era. Case report and literature review
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Martin-Iguacel, R., Kurtzhals, J., Jouvion, G., Nielsen, S. D., and Llibre, J. M.
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- 2014
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22. Microbiological aetiology of paediatric respiratory tract infections in Kyrgyzstan
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Osmonbaeva, Nargiza, Bloch, Joakim, Erkinbaeva, Aidai, Tilebalieva, Aigerim, Tolobekova, Raisa, Zhaparova, Meerim, Rogbo-Bengtsson, Aichatou, Isaeva, Elvira, Akylbekov, Azamat, Mademilov, Maamed, Baltabaeva, Erkingul, Esengeldieva, Gulbarchyn, Jensen, Christian Salgård, Nielsen, Alex Christian Yde, Kirkby, Nikolai Søren, Skov, Robert, Poulsen, Anja, Kjærgaard, Jesper, Sooronbaev, Talant, and Kurtzhals, Jørgen A. L.
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- 2025
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23. Insulin X10 revisited: a super-mitogenic insulin analogue
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Hansen, B. F., Kurtzhals, P., Jensen, A. B., Dejgaard, A., and Russell-Jones, D.
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- 2011
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24. The Mechanism of Protraction of Insulin Detemir, a Long-Acting, Acylated Analog of Human Insulin
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Havelund, Svend, Plum, Anne, Ribel, Ulla, Jonassen, Ib, Vølund, Aage, Markussen, Jan, and Kurtzhals, Peter
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- 2004
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25. Soluble, fatty acid acylated insulins bind to albumin and show protracted action in pigs
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Markussen, J., Havelund, S., Kurtzhals, P., Andersen, A. S., Halstrøm, J., Hasselager, E., Larsen, U. D., Ribel, U., Schäffer, L., Vad, K., and Jonassen, I.
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- 1996
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26. A new frequent allele is the missing link in the structural polymorphism of the human mannan-binding protein
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Madsen, Hans O., Garred, P., Kurtzhals, Joergen A. L., Lamm, Lars U., Ryder, Lars P., Thiel, Steffen, and Svejgaard, Arne
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- 1994
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27. Dispersion of linear gravity waves on a viscoelastic fluid in an horizontal canal
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Saasen, A., Kurtzhals, E., and Tyvand, P. A.
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- 1993
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28. Bloodstream Infections at Two Neonatal Intensive Care Units in Ghana
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Labi, Appiah-Korang, Enweronu-Laryea, Christabel C., Nartey, Edmund T., Bjerrum, Stephanie, Ayibor, Prosper K., Andersen, Leif P., Newman, Mercy J., and Kurtzhals, Jorgen A. L.
- Abstract
Supplemental Digital Content is available in the text.
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- 2021
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29. Traffic flow and microbial air contamination in operating rooms at a major teaching hospital in Ghana.
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Stauning, M.T., Bediako-Bowan, A., Andersen, L.P., Opintan, J.A., Labi, A.-K., Kurtzhals, J.A.L., Bjerrum, S., Stauning, Marius Tving, Bediako-Bowan, Antoinette, Andersen, Leif Percival, Opintan, Japheth A, Labi, Appiah-Korang, Kurtzhals, Jørgen, and Bjerrum, Stephanie
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Background: Current literature examining the relationship between door-opening rate, number of people present, and microbial air contamination in the operating room is limited. Studies are especially needed from low- and middle-income countries, where the risk of surgical site infections is high.Aim: To assess microbial air contamination in operating rooms at a Ghanaian teaching hospital and the association with door-openings and number of people present. Moreover, we aimed to document reasons for door-opening.Methods: We conducted active air-sampling using an MAS 100® portable impactor during 124 clean or clean-contaminated elective surgical procedures. The number of people present, door-opening rate and the reasons for each door-opening were recorded by direct observation using pretested structured observation forms.Findings: During surgery, the mean number of colony-forming units (cfu) was 328 cfu/m3 air, and 429 (84%) of 510 samples exceeded a recommended level of 180 cfu/m3. Of 6717 door-openings recorded, 77% were considered unnecessary. Levels of cfu/m3 were strongly correlated with the number of people present (P = 0.001) and with the number of door-openings/h (P = 0.02). In empty operating rooms, the mean cfu count was 39 cfu/m3 after 1 h of uninterrupted ventilation and 52 (51%) of 102 samples exceeded a recommended level of 35 cfu/m3.Conclusion: The study revealed high values of intraoperative airborne cfu exceeding recommended levels. Minimizing the number of door-openings and people present during surgery could be an effective strategy to reduce microbial air contamination in low- and middle-income settings. [ABSTRACT FROM AUTHOR]- Published
- 2018
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30. Surveillance of surgical site infection in a teaching hospital in Ghana: a prospective cohort study.
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Bediako-Bowan, A., Owusu, E., Debrah, S., Kjerulf, A., Newman, M.J., Kurtzhals, J.A.L., and Mølbak, K.
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Background: Surveillance systems for surgical site infections (SSIs), as a measure of patient safety, help health institutions devise strategies to reduce or prevent them. No surveillance systems exist to monitor SSIs in Ghana.Aim: To establish a system for monitoring trends and detecting outbreaks in order to create awareness of and control SSIs.Methods: An active 30-day surveillance was undertaken at the general surgical unit of the Korle Bu Teaching Hospital, from July 1st, 2017 to December 31st, 2018 to identify SSI. It involved a daily inpatient surveillance of patients who had had a surgical procedure, followed by post-discharge surveillance by means of a healthcare personnel-based survey and a patient-based telephone survey. We supplied quarterly feedback of results to surgeons.Findings: Among the 3267 patients included, 331 were identified with an SSI, a 10% incidence risk. Patients who acquired an SSI experienced increased morbidity including nine extra days in hospital and an adjusted relative mortality risk of 2.3 (95% confidence interval: 1.3 - 4.1; P=0.006) compared to patients without SSI. Forty-nine per cent (161/331) of SSIs were diagnosed post discharge using the healthcare personnel-based survey. The patient-based telephone survey contributed 12 additional cases. SSI incidence risk decreased from 12.8% to 7.5% during the study period.Conclusion: Post-discharge surveillance is feasible using existing healthcare personnel, and the results highlight the high risk and burden of SSIs in Ghana. A surveillance system with feedback for monitoring SSIs may contribute to reducing SSIs; however, firm conclusions regarding the impact need longer observation time. [ABSTRACT FROM AUTHOR]- Published
- 2020
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31. Genetic relationship between bacteria isolated from intraoperative air samples and surgical site infections at a major teaching hospital in Ghana.
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Stauning, M.A., Bediako-Bowan, A., Bjerrum, S., Andersen, L.P., Andreu-Sánchez, S., Labi, A-K., Kurtzhals, J.A.L., Marvig, R.L., and Opintan, J.A.
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Background: In low- and middle-income countries (LMICs) the rate of surgical site infections (SSI) is high, leading to negative patient outcomes and excess healthcare costs. A causal relationship between airborne bacteria in the operating room and SSI has not been established, at a molecular or genetic level. We studied the relationship between intraoperative airborne bacteria and bacteria causing SSI in an LMIC.Methods: Active air sampling using a portable impactor was performed during clean or clean-contaminated elective surgical procedures. Active patient follow-up consisting of phone calls and clinical examinations was performed 3, 14 and 30 days after surgery. Bacterial isolates recovered from SSI and air samples were compared by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) identification, ribotyping, whole genome sequencing (WGS), and metagenomic analysis.Results: Of 128 included patients, 116 (91%) completed follow-up and 11 (9%) developed SSI. Known pathogenic bacteria were isolated from intraoperative air samples in all cases with SSI. A match between air and SSI isolates was found by MALDI-TOF in eight cases. Matching ribotypes were found in six cases and in one case both WGS and metagenomic analysis showed identity between air- and SSI-isolates.Conclusion: The study showed high levels of intraoperative airborne bacteria, an SSI-rate of 9% and a genetic link between intraoperative airborne bacteria and bacteria isolated from SSIs. This indicates the need for awareness of intraoperative air quality in LMICs. [ABSTRACT FROM AUTHOR]- Published
- 2020
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32. Patent strategies for high-throughput screening systems: recent progress and future developments
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PH Jakobsen, P Kurtzhals, and F Poulsen
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Pharmacology ,Cover (telecommunications) ,Risk analysis (engineering) ,Computer science ,Drug Discovery ,Patent strategy ,Nanotechnology ,General Medicine ,Intellectual property ,Selection (genetic algorithm) - Abstract
High-throughput screening (HTS) systems for selection of drug candidates have been established in recent years. Patents and patent applications may cover different aspects of HTS, from assay structure to specific reagents used in HTS and, thus, protection of intellectual property rights within HTS may be obtained using different patent strategies. Broad functional claims are often listed in these patent applications. Users of HTS should be aware of these intellectual property rights before using HTS for selection of drug candidates.
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- 1998
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33. Heterologous synergistic interactions in concurrent experimental infection in the mouse with Schistosoma mansoni, Echinostoma revolution, Plasmodium yoelii, Babesia microti, and Trypanosoma brucei
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Christensen, N. Ø., Furu, P., Kurtzhals, J., and Odaibo, A.
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- 1988
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34. Insulin degludec: Multihexamer formation as new protraction mechanism leads to a long and flat glucose lowering effect
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B Wilhelm, J Aberle, P Kurtzhals, and T Heise
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Insulin degludec ,Glucose lowering ,medicine.medical_specialty ,Endocrinology ,Mechanism (biology) ,Chemistry ,Endocrinology, Diabetes and Metabolism ,Internal medicine ,Internal Medicine ,medicine ,General Medicine - Published
- 2013
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35. Engineering predictability and protraction in a basal insulin analogue: the pharmacology of insulin detemir
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P Kurtzhals
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medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Injections, Subcutaneous ,Medicine (miscellaneous) ,Plasma protein binding ,Pharmacology ,Absorption ,Insulin Detemir ,Internal medicine ,Diabetes mellitus ,Medicine ,Humans ,Hypoglycemic Agents ,Insulin ,Receptor ,Serum Albumin ,Insulin detemir ,Nutrition and Dietetics ,business.industry ,Albumin ,medicine.disease ,Receptor, Insulin ,Insulin, Long-Acting ,Endocrinology ,Tolerability ,Pharmacodynamics ,Delayed-Action Preparations ,business ,medicine.drug ,Protein Binding - Abstract
The suboptimal nature of the absorption profiles of human insulin formulations following subcutaneous administration has prompted the development of insulin analogues better suited for therapeutic use in diabetes mellitus. A particular challenge has been to engineer long-acting agents that do not produce unduly variable responses from one injection to another. One recent approach that has met with success has been to acylate, the insulin molecule with a fatty acid, thereby enabling reversible albumin binding. The first clinically available agent of this type is insulin detemir. Pharmacological studies have established that this principle is effective in prolonging action, primarily by retarding absorption. The solubility of insulin detemir in the vial and after injection and an important buffering mechanism effected by plasma albumin binding explain a significant decrease in within-subject variability of pharmacodynamic response observed in repeat isoglycaemic clamp studies where insulin detemir was compared to other basal insulin products. Owing to the extremely high ratio of albumin-binding sites to insulin detemir molecules at therapeutic concentrations, no safety considerations have been identified pertaining to albumin binding. The insulin detemir molecule retains the molecular pharmacological properties of native human insulin, including a physiological balance between metabolic and mitogenic potencies. Thus, insulin detemir offers the promise of an improved tolerability:efficacy ratio in the clinical setting.
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- 2004
36. 40(th) EASD Annual Meeting of the European Association for the Study of Diabetes : Munich, Germany, 5-9 September 2004
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S. Artigas, A V Dreval, Mark I. McCarthy, C Watson, Peter H. Bennett, M Quint, Y Ikeda, E Alpert, F Schiele, H Sekihara, Erik Gylfe, P Lowe, J Kuhlmann, Alain Golay, V Longo, Shahidul Alam Khan Akm., L G Mantovani, M Zawodniak-Szalapska, G Winkler, T Harrity, L Virág, U Johne, Kuo S-W., Linda C Tapsell, J Rodriguez, Michel Komajda, K Kankova, Carole A. Cull, M Sporna, E Estilles, U Ribel, M C Spruce, E Buzzigoli, T Prazak, J K McLaughlin, M K Lingohr, M Lim, F Calara, A Siebenhofer, G Meregalli, Roberto Anichini, A D Baron, R Kurashvili, P C Butler, G I Fantus, T. E. De Gooyer, Park Y-M., R. Walther, S Heinrich, Agnieszka Zawiejska, S Mukherjee, Nikolaos Papanas, G Wong, Ian D. Caterson, David M. Maahs, Shuichi Kaneko, Alexandra E. Butler, Francisco Javier Ampudia-Blasco, O N Kong, Attali J-R., C A Hedman, K Oshinyemi, Nicolle Müller, I C Cranston, N Okumus, M V Vlaiculescu, Balasubramanian Ravikumar, W W Cheatham, K Mukasa, K B Biswas, Annunziata Lapolla, Phil McEwan, G Mader, Gilles Chassot, Dragi Anevski, Werner A. Scherbaum, M Donath, C Hesselmann, R A Gandhi, David E. Moller, Ezio Bonifacio, C Garcia, V Ifandi, P Hornnes, Nieuwenhoven Fav., C Puech, S Pérez-Del-Pulgar, Kim S-R., G Hines, C Rubio Terrés, Michael Gaster, N. Hosszufalusi, A Scholze, Andrew A. Young, Stavros Liatis, F Hariri, S Tan, Paul Valensi, Allan E. Karlsen, J Kim, E. Moberg, J Kaiser, L Berman, G Nelson, A Altkrüger, P Kothare, D B Cook, S Doran, G. van Dijk, Shahnaz Shahinfar, Kim C-S., P Stahl, M Manousaki, S Sigrist, S K Lim, M. P. Stern, A Guberti, C Rezzani, J McKenney, Karl Thomaseth, Sofia Carlsson, M Julia, R Brillante, I Rubesova, T Darkow, E Matsumoto, Wendy M. Macfarlane, M Di Martino, G Bardini, Rossella Menghini, D Duhot, E Farcasiu, Annalisa Natalicchio, I Lindner, J Buvat, Christian L. Brand, Harry Dorchy, Iwona Pietrzak, Z T Luo, P Home, M Ekelund, Jesper Gromada, Kristine Færch, F Piarulli, H Kim, R Mentel, Zsuzsanna K. Zsengellér, Dullaart Rpf., Anton Luger, Thomas A. Pearson, V Manicardi, P Rösen, Feng Y-M., R Morganti, Lars Hansen, Demuth H-U., Haruo Kasai, A Shostak, Rudi Steffensen, G Taylor, Markolf Hanefeld, C Santini, E Hamaguchi, Roberto Miccoli, F Storms, M Cooper, Y Lee, Allison E. Aiello, P Smith, T Suehiro, K Treece, M Waluś, Timothy A Welborn, Simone Baltrusch, E Kontela, S Chai, J Crean, H Yokoyama, Johan G. Eriksson, Rafael Hernández Hernández, J Rodríguez-Saldaña, M P Tornero, G Formoso, D. Lovell, E Bingham, A Mylonakis, M Manteghetti, D Fedele, Antonio Martín-Duce, Ralph A. DeFronzo, D Salcedo, Kurt Højlund, Antonio Petrone, Sheu Whh., C Gutierrez, Flavia Pricci, S Kurita, Z G Abbas, M M Benedetti, Philippe A. Halban, Daniel J. Cox, O Ljungkvist, Justine Davies, J Palsgaard, Lars Sjöström, E Bosi, L Janin-Manificat, W. F. Kelly, M. Fernandez, E Colak, O V Mulyarchik, B Kronshage, F Lang, M Erfurth, Takashi Kadowaki, N Jendrike, U Walter, J Wishart, Y. Neye, D Kim, N Furuhashi, M Barsotti, D Florow, L Ke, L Borgquist, N C Jackson, Ffolliott M. Fisher, V Baskar, K Yoshioka, Bryan A. Wolf, G Chabrier, R Skoumal, Livio Luzi, H Kose, I Pharisien, B. Klein, H Winiarska, M C Johnson, L Griffiths, Nonna Kravchun, C Combe, Baptist Gallwitz, J Zdychova, L Skorda, Jorma Ilonen, W Gao, I N Steen, A Terrinoni, P D Ambery, W Kern, C M Kusminski, Cho M-H., Paolo Pozzilli, Louise G. Grunnet, E Schönle, David R Matthews, Robert W. Taylor, Y Cohen, Kim H-S., M P Eccles, N B Tutuncu, D McDowell, Richard M. Bergenstal, K Takamatsu, T Steiner, Jaan Palgi, Valdemar Grill, N Niculescu, G Federici, S Lehto, P. M. McKeigue, M Barone, Michael E. Trautmann, S Smirnov, J Mannion, M Eto, C Rousseau, M Conti, C S Ernest, Antonio Ceriello, D H Schweitzer, Jung E-D., Andreas Festa, Avijit Lahiri, A Shepelkevich, A Murro, A Kollmann, Jonathan R.S. Arch, R Landgraf, Son H-Y., I Engelsberger, E Agardh, S Rodríguez-Mulero, P J Kraml, K Lee, D. F. Du Toit, E Kim, G Fadini, Williams Ajk., Philip Home, M B Antcieferov, C Perlemoine, D Perrea, Song X-L., D Ruggieri, Krister Bokvist, Heidi Sørensen, Bilbao, G Yoshino, J P Taylor, Shen H-M., S M Furier, R Urquhart, J Wohlgelernter, Jianping Weng, T. Baba, Q Hong, C Silva, Castaigne J-P., M Felaco, X X Zhang, M Jaroň, Milla Rosengård-Bärlund, J G Papp, Toshio Miyata, Lervang H-H., Park M-K., I Kinalska, A Long, Oomen Phn., N Kogawa, Ippolita Patrizia Patera, S. Karadeniz, Dinesh Selvarajah, D S Chung, A Wensaas, Richard Imrich, M Recasens, J Ruxer, O Buchea, E Wilpart, S P Stepanenko, Le Ttd., H Ohgawara, Mariaconsuelo Valentini, A Mondok, M Peltonen, Marianne O. Larsen, K Chatzianagnostou, Agneta Ståhle, A L Ferrari, L Bordier, F Maingrette, A Matsuda, G Vukomanovic, Jakob D. Wikstrom, T Yamakita, E Gorostiaga, J Jin, B Gopalan, Heinz Drexel, S Hewitt, Rury R. Holman, C Dieterle, T L Ruchti, N Asatiani, M Sidira, A Iezzi, A J Sommerfield, D Châtenet, M L Olsen, R Bergemann, C Koehler, T L Kuraeva, B Balas, Christian Berne, E Santos-Mazo, G Smith, A Siejka, R Kožnarová, A Mattina, S Sheikh, A Adomeit, M Rasmussen, J. Fagerudd, N Busciantella Ricci, Nuria Vilarrasa, E Hammar, T L Thoms, L Aydın, Ron G. Rosenfeld, A Nikolajuk, R Gos, C L Morgan, H L Yu, D Dheelchand, S Ramrath, N Boudriga, Jerome I. Rotter, C Jahannault, W M Weston, Folke Lindgärde, M Hertlova, D Knight, A Monroy-Mayorga, E Pardini, A Chamson-Reig, B Franke, Janie McCluskey, Joseph Bryan, C Nikolopoulou, Christie M. Ballantyne, Fausto Santeusanio, L Pegoraro, M Lee, A Klimenko, S Jaiveer, K. Pettersson-Fernholm, Michael A. 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Paulin, S, Marcu, S, Tauveron, I, Zimmermann, C, Schiele, F, Seronde, M, Vautrin, P, Lusson, J, Thieblot, P, Bernard, Y, Mistry, A, Pye, M, Peovska, I, Maksimovic Pavlovic, J, Vavlukis, M, Pop Gorceva, D, Bosevski, M, Scognamiglio, R, Negut, C, De Kreutzenberg, S, Madonna, R, De Caterina, R, Willerson, J, Geng, Y, Vahsen, S, Ledwig, D, Ramrath, S, Frantz, S, Schmidt, I, Calvillo, L, Dienesch, C, Elbing, I, Bischoff, H, Ertl, G, Bauersachs, J, Davydov, A, Mkrtum'Yan, A, Baranova, L, Ikeda, Y, Suehiro, T, Osaki, F, Ota, K, Arii, K, Kumon, Y, Hashimoto, K, Doney, A, Morris, A, Palmer, C, Byun, S, Doo, H, Pagnin, E, Calo, L, Fadini, G, Kubaszek, A, Chai, S, Chai, Q, Rasmussen, L, Ledet, T, Wogensen, L, Lengyel, C, Varró, A, Virág, L, Magyar, J, Bíró, T, Jost, N, Skoumal, R, Nánási, P, Tóth, M, Horkay, F, Papp, J, Zacharopoulou, O, Athanaselis, S, Tsokos, N, Doupis, J, Psallas, M, Cokkinos, D, Pavlatos, S, Liatis, S, Akhobadze, T, Dzneladze, L, Samarguliani, I, Taskiran, M, Rasmussen, V, Jensen, G, Fisher, A, Petrovsky, N, Srikusalanukul, W, Budge, M, Trifunovic zamaklar, D, Zivkovic, M, Jelic, V, Vukomanovic, G, Ristic, A, Seferovic, P, Costa, J, Duarte, S, Manley, S, Sailesh, S, Venkataraman, A, Haider, Y, Groza, I, Oprean, M, Ardelean, A, Morosanu, A, Darkow, T, Vanderplas, A, Mamas, M, Mcelduff, P, Burns, J, Edwards, R, Fitchet, A, Young, R, Gibson, J, Lichiardopol, R, Niculescu, N, Totora, A, Pencea, C, Tomescu, I, Cinteza, M, Manicardi, V, Coscelli, C, Navazio, A, Catellani, E, Michelini, M, Dall'Asta, D, Guberti, A, Piazza, A, Gasparini, E, Pantaleoni, M, Guiducci, U, Manari, A, Sejil, S, Janand delenne, B, Avierinos, J, Habib, G, Labastie, N, Vague, P, Lassmann vague, V, Luźniak, P, Tatoń, J, Wojciechowska Luźniak, A, Zairis, M, Lyras, A, Patsourakos, N, Tsirimbis, V, Foussas, S, Lupón, J, Urrutia, A, Herreros, J, González, B, Coll, R, Altimir, S, Prats, M, Valle, V, Abreu padí, C, Rábago, G, Ivanova, L, Brasacchio, D, Harno, E, Keenan, A, Li, H, Lu, Z, Ke, L, Liu, H, Jeong, I, Chae, M, Choi, M, Yoo, H, Kim, C, Yun, M, Na, M, Kang, Y, Kong, O, Son, S, Kim, I, Tanaka, N, Hosoi, M, Matsuyama, Y, Fukumoto, M, Yamakita, T, Yoshioka, K, Ishii, T, Sato, T, Fujii, S, Aoki, T, Shibata, T, Mizutani, N, Suzuki, J, Fowelin, J, Samuelsson, P, Brandrup wogsen, G, Okumura, K, Tokmakova, A, Staroverova, D, Antcieferov, M, Shutichina, I, Kuntchevich, G, Vriesendorp, T, Morélis, Q, Legemate, D, Schaper, F, Mainas, E, Gkioulmpasanis, I, Panagiotou, I, Vassilikos, G, Skorda, L, Sidira, M, Christoforidou, M, Alaveras, A, Artikis, V, Evdemon, E, Lechleitner, M, Koch, T, Ebenbichler, C, Sturm, W, Moretti, L, Moruzzo, D, Boldrini, E, Pandolfo, C, Kameyama, M, Iwasa, R, Cho, M, Nam, J, Huh, K, Kaplar, M, Paragh, G, Erdei, A, Csongradi, E, Garai, I, Varga, J, Galuska, L, Udvardy, M, Higa, M, Kaneko, Y, Hiroi, N, Koziarska, D, Nowacki, P, Majkowska, L, Luzniak, P, Wojciechowska luźniak, A, Tushuizen, M, Nieuwland, R, Snoeck, D, Sturk, A, Diamant, M, Aguiar, L, Bahia, L, Villela, N, Laflor, C, Conde, C, Bottino, D, Dorigo, D, Bouskela, E, Pu, S, Luo, Z, Lam, K, Dan, Q, Xu, A, Shen, J, Cheng, K, Xu, J, Thamer, C, Stefan, N, Haap, M, Heller, E, Tschritter, O, De Prado, A, Ortiz, A, Ybarra, J, Gich, I, Pou, J, Ehren, M, Roggenland, D, Reinsen, B, Klein, H, Rittig, K, Stock, J, Kocher, B, Balletshofer, B, Shon, H, Chung, D, Nakatani, Y, Matsuhisa, M, Kaneto, H, Hatazaki, M, Yoshiuchi, K, Katakami, N, Kawamori, D, Ohtoshi, K, Sakamoto, K, Matsuoka, T, Ozawa, K, Ogawa, S, Hori, M, Yamasaki, Y, Zitouni, K, Harry, D, Nourooz zadeh, J, Earle, K, Olesen, P, Franco, L, Corvaja, C, Semplicini, A, Ceylan işık, A, Arı, N, Rösen, P, Lee, I, Park, K, Jung, E, Shin, D, Jo, S, Obuobie, K, Prakash, P, Hanna, F, Lazarus, J, Varadhan, L, Gurushankar, J, James, D, Sheikh, S, Gaede, P, Zou, D, Vilarrasa, N, Perez maraver, M, Mena, E, Perez, D, Setti, G, Buckingham, R, Urbančič, V, Stefanovska, A, Bernjak, A, Ažman juvan, K, Kocijančič, A, Glowania, A, Filters, T, Fosmark, D, Torjesen, P, Kilhovd, B, Berg, T, Sandvik, L, Hanssen, K, Mentink, C, Donchenko, G, Stepanenko, S, Maingrette, F, Deng, H, Lindenmair, A, Freudenthaler, A, Baumgartner parzer, S, Nizheradze, K, Khoruzhenko, A, Tronko, N, Sheu, W, Ou, H, Shen, H, Lin, T, Wu, H, Yang, C, Mogylnytska, L, Schmoelzer, I, Davies, J, Band, M, Struthers, A, Prázný, M, Škrha, J, Kasalová, Z, Neelotpol, S, Jahan, P, Kauschke, S, Harrop, C, Schäfer, A, Widder, J, Eigenthaler, M, Walter, U, Uchimura, I, Ikebukuro, M, Kaibara, M, Hirata, M, Helal, R, Pervin, F, Yang, X, Jansson, P, Nagaev, I, Jack, M, Carvalho, E, Sunnerhagen, K, Cam, M, Cushman, S, Smith, U, Creely, S, Farmer, J, Gustafson, B, Kusminski, C, Krusinova, E, Wohl, P, Klementova, M, Lanska, V, Mcdougall, C, Kelly, I, Abbas, Z, Lutale, J, Archibald, L, Karunajeewa, H, Stingemore, N, Stuccio, G, Mcgechie, D, Muller, L, Hak, E, Goudzwaard, W, Montorsi, F, Homering, M, Sprenger, K, Goldstein, I, Asnaghi, V, Ferrari, G, Rastaldi, M, Gabellini, D, Dell'Antonio, G, Maestroni, A, Ruggieri, D, Luzi, L, Piemonti, L, Zerbini, G, Anafaroglu, I, Tutuncu, N, Sultana, M, Siddiqua, N, Iwasaki, T, Nakajima, A, Yoneda, M, Mukasa, K, Tanaka, S, and Sekihara, H
- Subjects
0303 health sciences ,medicine.medical_specialty ,business.industry ,EASD ,Endocrinology, Diabetes and Metabolism ,Human physiology ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Diabetes mellitus ,Family medicine ,Internal Medicine ,Medicine ,business ,030217 neurology & neurosurgery ,030304 developmental biology - Published
- 2004
37. Decreased Red Blood Cell Deformability Contributes to Loss of Splenic Filtration Function and Variations in Spleen Size in Children with Sickle Cell Anaemia
- Author
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Nardo-Marino, Amina, Glenthøj, Andreas, Brewin, John N., Petersen, Jesper, Braunstein, Thomas H., Kurtzhals, Jørgen A.L., Williams, Thomas N., and Rees, David C.
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- 2022
- Full Text
- View/download PDF
38. Molecular Detection of the Carriage Rate of Four Intestinal Protozoa with Real-Time Polymerase Chain Reaction: Possible Overdiagnosis of Entamoeba histolytica in Nigeria.
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Efunshile, Michael A., Ngwu, Bethrand A. F., Kurtzhals, Jørgen A. L., Sahar, Sumrin, Konig, Brigitte, and Stensvold, Christen R.
- Published
- 2015
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- View/download PDF
39. How to achieve a predictable basal insulin?
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P. Kurtzhals
- Subjects
Models, Molecular ,medicine.medical_specialty ,Protein Conformation ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Molecular Sequence Data ,Subcutaneous injection ,Endocrinology ,Pharmacokinetics ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,Insulin ,Amino Acid Sequence ,Pancreatic hormone ,Insulin detemir ,Clinical Trials as Topic ,biology ,business.industry ,Albumin ,Reproducibility of Results ,General Medicine ,medicine.disease ,Insulin receptor ,Diabetes Mellitus, Type 1 ,Diabetes Mellitus, Type 2 ,biology.protein ,business ,medicine.drug - Abstract
The development of insulin analogues over the last two decades have aimed at optimising the pharmacokinetic profile of subcutaneously injected insulin for therapeutic use in diabetes mellitus. Rapid acting analogues were successfully engineered and marketed in the late 1990's. In engineering long-acting analogues it has been a particular challenge to obtain action profiles that would be predictable from day to day in the same person. The most recent approach has been to acylate the insulin molecule with a fatty acid which provides the insulin molecule with a specific affinity for albumin. The first clinically available agent of this type is insulin detemir. Pharmacological studies have shown that reversible albumin binding will protract absorption following subcutaneous injection but still allow the insulin molecule to be recognised by the insulin receptor following dissociation from the carrier protein. Moreover, the molecular features of insulin detemir are attractive in that the molecule can be formulated as a neutral aqueous solution and does not precipitate after injection. Together with an important buffering mechanism effected by plasma albumin binding, this explains a highly significant reduction of within-subject variability of pharmacodynamic response observed in repeat isoglycaemic clamp studies where insulin detemir was compared to other basal insulin products. No safety considerations have been identified in using albumin as an insulin carrier to protract and buffer insulin action. In assessing the clinical attractiveness of insulin analogues, it is furthermore critically important to consider how the molecular modifications impact efficacy and safety. A number of pharmacological studies have shown that insulin detemir overall retains the molecular pharmacological properties of native human insulin, including a physiological balance between metabolic and mitogenic potencies. Taken together, insulin detemir provides an attractive novel approach for predictive basal insulin delivery to people with diabetes.
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- 2005
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40. Epidemiological Study of the Association Between Malaria and Helminth Infections in Nigeria.
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Efunshile, Akinwale Michael, Olawale, Temitope, Stensvold, Christen Rune, Kurtzhals, Jørgen A. L., and König, Brigitte
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- 2015
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41. Outbreak of Pneumocystis Pneumonia in Renal and Liver Transplant Patients Caused by Genotypically Distinct Strains of Pneumocystis jirovecii
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Rostved, Andreas A., Sassi, Monica, Kurtzhals, Jørgen A.L., Sørensen, Søren Schwartz, Rasmussen, Allan, Ross, Christian, Gogineni, Emile, Huber, Charles, Kutty, Geetha, Kovacs, Joseph A., and Helweg-Larsen, Jannik
- Abstract
An outbreak of 29 cases of Pneumocystis jiroveciipneumonia (PCP) occurred among renal and liver transplant recipients (RTR and LTR) in the largest Danish transplantation centre between 2007 and 2010, when routine PCP prophylaxis was not used.
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- 2013
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42. CNS Hypoxia Is More Pronounced in Murine Cerebral than Noncerebral Malaria and Is Reversed by Erythropoietin
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Hempel, Casper, Combes, Valery, Hunt, Nicholas Henry, Kurtzhals, Jørgen Anders Lindholm, and Grau, Georges Emile Raymond
- Abstract
Cerebral malaria (CM) is associated with high mortality and risk of sequelae, and development of adjunct therapies is hampered by limited knowledge of its pathogenesis. To assess the role of cerebral hypoxia, we used two experimental models of CM, Plasmodium bergheiANKA in CBA and C57BL/6 mice, and two models of malaria without neurologic signs, P. bergheiK173 in CBA mice and P. bergheiANKA in BALB/c mice. Hypoxia was demonstrated in brain sections using intravenous pimonidazole and staining with hypoxia-inducible factor-1α–specific antibody. Cytopathic hypoxia was studied using poly (ADP-ribose) polymerase-1 (PARP-1) gene knockout mice. The effect of erythropoietin, an oxygen-sensitive cytokine that mediates protection against CM, on cerebral hypoxia was studied in C57BL/6 mice. Numerous hypoxic foci of neurons and glial cells were observed in mice with CM. Substantially fewer and smaller foci were observed in mice without CM, and hypoxia seemed to be confined to neuronal cell somas. PARP-1–deficient mice were not protected against CM, which argues against a role for cytopathic hypoxia. Erythropoietin therapy reversed the development of CM and substantially reduced the degree of neural hypoxia. These findings demonstrate cerebral hypoxia in malaria, strongly associated with cerebral dysfunction and a possible target for adjunctive therapy.
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- 2011
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43. Differential MicroRNA Expression in Experimental Cerebral and Noncerebral Malaria
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El-Assaad, Fatima, Hempel, Casper, Combes, Valéry, Mitchell, Andrew J., Ball, Helen J., Kurtzhals, Jørgen A. L., Hunt, Nicholas H., Mathys, Jean-Marie, and Grau, Georges E. R.
- Abstract
ABSTRACTMicroRNAs (miRNAs) are posttranscriptional regulatory molecules that have been implicated in the regulation of immune responses, but their role in the immune response to Plasmodiuminfection is unknown. We studied the expression of selected miRNAs following infection of CBA mice with Plasmodium bergheiANKA (PbA), which causes cerebral malaria (CM), or Plasmodium bergheiK173 (PbK), which causes severe malaria but without cerebral complications, termed non-CM. The differential expression profiles of selected miRNAs (let-7i, miR-27a, miR-150, miR-126, miR-210, and miR-155) were analyzed in mouse brain and heart tissue by quantitative reverse transcription-PCR (qRT-PCR). We identified three miRNAs that were differentially expressed in the brain of PbA-infected CBA mice: let7i, miR-27a, and miR-150. In contrast, no miRNA changes were detected in the heart, an organ with no known pathology during acute malaria. To investigate the involvement of let-7i, miR-27a, and miR-150 in CM-resistant mice, we assessed the expression levels in gamma interferon knockout (IFN-γ−/−) mice on a C57BL/6 genetic background. The expression of let-7i, miR-27a, and miR-150 was unchanged in both wild-type (WT) and IFN-γ−/−mice following infection. Overexpression of these three miRNAs during PbA, but not PbK, infection in WT mice may be critical for the triggering of the neurological syndrome via regulation of their potential downstream targets. Our data suggest that in the CBA mouse at least, miRNA may have a regulatory role in the pathogenesis of severe malaria.
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- 2011
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44. Artesunate plus amodiaquine combination therapy: reviewing the evidence
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Adjei, George O., Kudzi, William, Dodoo, Alexander, and Kurtzhals, Jorgen A.L.
- Abstract
The combination of artesunate plus amodiaquine (AS/AQ) is, next to the fixed‐dose combination of artemether‐lumefantrine, the most widely adopted artemisinin combination therapy (ACT) regimen being used as first‐line therapy for uncomplicated malaria by National Malaria Control Programs in sub‐Saharan Africa. In contrast to other ACT regimens in current use, on which reviews of the available evidence on safety and efficacy have been periodically published, no, or few summaries of the extensive data available on the safety and efficacy of this widely used ACT are available in the published literature. The available evidence on AS/AQ indicates high efficacy of this combination in children, variable tolerability in adults, and an interaction between artesunate and amodiaquine that could have implications for medium term efficacy or safety of the combination. In this article, a review of the available evidence on the efficacy and safety on AS/AQ, with a particular focus on parameters that could have operational significance for malaria control in endemic areas, is presented and discussed. Drug Dev Res 71: 33–43, 2010. © 2009 Wiley‐Liss, Inc.
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- 2010
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45. Effect of Concomitant Artesunate Administration and Cytochrome P4502C8 Polymorphisms on the Pharmacokinetics of Amodiaquine in Ghanaian Children with Uncomplicated Malaria
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Adjei, George O., Kristensen, Kim, Goka, Bamenla Q., Hoegberg, Lotte C. G., Alifrangis, Michael, Rodrigues, Onike P., and Kurtzhals, Jorgen A. L.
- Abstract
ABSTRACTArtesunate (AS) is used in combination with amodiaquine (AQ) as first-line treatment for uncomplicated malaria in many countries. We investigated the effect of concomitant AS administration on the pharmacokinetics of AQ and compared concentrations of desethylamodiaquine (DEAQ), the main metabolite of AQ, in plasma between patients with different variants of the cytochrome P4502C8 (CYP2C8) gene. A two-compartment model was fitted to 169 plasma DEAQ concentrations from 103 Ghanaian children aged 1 to 14 years with uncomplicated malaria treated either with AQ alone (n= 15) or with AS plus AQ (n= 88). The population clearance of DEAQ appeared to increase nonlinearly with body weight, and the central volume of distribution of DEAQ was higher (P< 0.001) in the AS-plus-AQ group than in the AQ-only group. The maximum plasma DEAQ concentration was higher (P< 0.001), and the population distribution half-life was shorter (P< 0.01), in the AQ-only group than in the AS-plus-AQ group. The total areas under the plasma DEAQ concentration-time curves (P= 0.68) and elimination half-lives (P= 0.39) were similar for the two groups. There was a high frequency (0.179) of the non-wild-type allele of CYP2C8, but no differences between CYP2C8 genotypes with regard to AQ efficacy or safety were evident. The sample size, however, was limited, so monitoring of AQ toxicity in the study area is still indicated. The nonlinear clearance of DEAQ and the wide variability in kinetic parameters have safety implications for weight-based dosing of higher-body-weight children with AQ. The pharmacokinetics of artemisinin combination therapies should be studied in malaria patients, because the rapid parasite clearance caused by the artemisinin may affect the kinetics of the partner drug and the combination.
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- 2008
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46. Factors Contributing to the Development of Anaemia in Plasmodium falciparum Malaria: What about Drug-Resistant Parasites?
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Quashie, Neils Ben, Akanmori, Bartholomew D., Ofori-Adjei, David, Goka, Bamenla Q., and Kurtzhals, Jorgen A. L.
- Abstract
A major manifestation of complicated malaria especially among children is severe anaemia, the pathogenesis of which is not well understood. Among other factors, suppression of the bone marrow's response to erythropoietin, which is rapidly reversed after successful treatment of the malaria, has been implicated in its pathogenesis. Since resolution of malaria restores erythropoiesis, we hypothesized that drug-resistant strains of Plasmodium falciparum would increase the risk of severe anaemia developing from initially uncomplicated malaria. Using both in vivo and in vitro drug-sensitivity tests we compared the prevalence of drug-resistant malaria between severe malarial anaemia (SA) and non-anaemic malaria (NAM) patients. Assessment of treatment outcome using the WHO in vivo criteria showed no significant difference in parasite resistance between the two groups. The mean parasite clearance time was also comparable. Treatment failures of about 14 per cent and 12 per cent were observed between SA and NAM patients respectively. The in vitro drug susceptibility test showed overall mean IC50 values of 0.41×10−6 mol/l and 0.32×10−6 mol/l blood for SA and NAM groups respectively. Geometric mean pre-treatment blood levels of chloroquine did not differ much between the two groups. Findings from this study could not therefore implicate drug-resistant parasites in the pathogenesis of severe malarial anaemia.
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- 2006
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47. Insulin detemir: from concept to clinical experience
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Home, Philip and Kurtzhals, Peter
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Insulin detemir (Levemir®, Novo Nordisk) is a novel, biologically engineered analogue of human insulin that has been successfully developed for clinical use in diabetes as a basal insulin. Its unique mechanism of prolongation of action, achieved through acylation to give reversible albumin binding and additional self-association, goes some way to addressing one of the fundamental limitations of previously available, subcutaneously administered basal insulins, a high level of within-person variability in time–action profile from one injection to another. The pharmacological profile of insulin detemir, characterised in a series of studies, suggested it had the potential to offer efficacy and tolerability advantages in the clinical setting. Such advantages, in comparison to NPH (neutral protamine Hagedorn) insulin, have subsequently been illustrated in trials. Despite glucose control targets that are identical to comparators, insulin detemir achieved levels of glycaemic control that, overall, were at least as good as NPH insulin in the Phase III development programme, with lower variability being a consistent finding. This was associated with consistent risk reductions in nocturnal hypoglycaemic events, which are closely linked with the basal component of insulin therapy. Another consistent finding has been a significantly reduced propensity for weight gain. An all-analogue regimen combining insulin detemir with the rapid-acting insulin aspart illustrated the potential benefits achievable when insulins that are designed to achieve defined pharmacokinetic profiles are employed clinically; blood glucose control, including hypoglycaemia, was significantly superior to a human insulin-based mealtime plus basal regimen. Insulin detemir is, therefore, a valuable addition to the range of exogenous insulins, as it should enable treatment regimens to be constructed that offer good outcomes of efficacy and tolerability.
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- 2006
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48. Pretreatment Blood Concentrations of Chloroquine in Patients with Malaria Infection: Relation to Response to Treatment
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Quashie, Neils Ben, Akanmori, Bartholomew D., Goka, Bamenla Q., Ofori-Adjei, David, and Kurtzhals, Jorgen A. L.
- Abstract
Resistance of Plasmodium falciparum to chloroquine has been reported in many areas in Ghana. Most of these reports, which are from hospital-based studies, indicate RI and RII rather than RIII type of resistance. Since high pretreatment levels of chloroquine have also been measured in patients with malaria infection in Ghana, we hypothesized that the ‘added effect’ of the pretreatment ingested drug to the full dose given at the hospital may be responsible for the low proportion of RIII type of resistance observed. To ascertain this, pretreatment blood levels of chloroquine were correlated with treatment outcomes in 231 paediatric malaria patients, referred to a major hospital in Ghana. The rate of parasite clearance and prevalence of recrudescence, 14 days post-treatment, were determined for each patient. Results from this study showed no correlation between pretreatment chloroquine levels and day 0 parasitaemia. Two hundred and seven patients (89.6 per cent) had parasites that were sensitive to chloroquine whilst 24 (10.4 per cent) had resistant parasites. Of the latter group 17, six, and one patients had P. falciparum parasites, which were resistant at RI, RII and RIII levels, respectively. Seventy-five per cent of the patients without any detectable pretreatment blood chloroquine had parasites that were sensitive to chloroquine whilst 89.8 per cent, 98 per cent, and 100 per cent with pretreatment blood chloroquine concentration ranges of 0.5–100.5 ng/ml, 100.5–200 ng/ml, and >200 ng/ml, respectively, had chloroquine-sensitive parasites. An inverse relationship was thus observed between pretreatment blood chloroquine concentration and the degree of resistance in this study. We conclude that pre-hospital treatment ingested chloroquine contributes significantly to the resolution of malaria in children in Ghana, in the presence of chloroquine resistance.
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- 2005
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49. Antibodies to the N-Terminal Block 2 of Plasmodium falciparumMerozoite Surface Protein 1 Are Associated with Protection against Clinical Malaria
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Cavanagh, David R., Dodoo, Daniel, Hviid, Lars, Kurtzhals, Jørgen A. L., Theander, Thor G., Akanmori, Bartholomew D., Polley, Spencer, Conway, David J., Koram, Kojo, and McBride, Jana S.
- Abstract
ABSTRACTThis longitudinal prospective study shows that antibodies to the N-terminal block 2 region of the Plasmodium falciparummerozoite surface protein 1 (MSP-1) are associated with protection against clinical malaria in an area of stable but seasonal malaria transmission of Ghana. Antibodies to the block 2 region of MSP-1 were measured in a cohort of 280 children before the beginning of the major malaria transmission season. The cohort was then actively monitored for malaria, clinically and parasitologically, over a period of 17 months. Evidence is presented for an association between antibody responses to block 2 and a significantly reduced risk of subsequent clinical malaria. Furthermore, statistical survival analysis provides new information on the duration of the effect over time. The results support a conclusion that the block 2 region of MSP-1 is a target of protective immunity against P. falciparumand, thus, a promising new candidate for the development of a malaria vaccine.
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- 2004
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50. Geographical and Temporal Conservation of Antibody Recognition of Plasmodium falciparumVariant Surface Antigens
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Nielsen, Morten A., Vestergaard, Lasse S., Lusingu, John, Kurtzhals, Jørgen A. L., Giha, Haider A., Grevstad, Berit, Goka, Bamenla Q., Lemnge, Martha M., Jensen, James B., Akanmori, Bartholomew D., Theander, Thor G., Staalsoe, Trine, and Hviid, Lars
- Abstract
ABSTRACTThe slow acquisition of protection against Plasmodium falciparummalaria probably reflects the extensive diversity of important antigens. The variant surface antigens (VSA) that mediate parasite adhesion to a range of host molecules are regarded as important targets of acquired protective immunity, but their diversity makes them questionable vaccine candidates. We determined levels of VSA-specific immunoglobulin G (IgG) in human plasma collected at four geographically distant and epidemiologically distinct localities with specificity for VSA expressed by P. falciparumisolates from three African countries. Plasma levels of VSA-specific IgG recognizing individual parasite isolates depended on the transmission intensity at the site of plasma collection but were largely independent of the geographical origin of the parasites. The total repertoire of immunologically distinct VSA thus appears to be finite and geographically conserved, most likely due to functional constraints. Furthermore, plasma samples frequently had high IgG reactivity to VSA expressed by parasites isolated more than 10 years later, showing that the repertoire is also temporally stable. Parasites from patients with severe malaria expressed VSA (VSASM) that were better recognized by plasma IgG than VSA expressed by other parasites, but importantly, VSASM-type antigens also appeared to show substantial antigenic homogeneity. Our finding that the repertoire of immunologically distinct VSA in general, and in particular that of VSASM, is geographically and temporally conserved raises hopes for the feasibility of developing VSA-based vaccines specifically designed to accelerate naturally acquired immunity, thereby enhancing protection against severe and life-threatening P. falciparummalaria.
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- 2004
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