Search

Your search keyword '"Linde, H.-J."' showing total 113 results
Start Over Author "Linde, H.-J." Language english
113 results on '"Linde, H.-J."'

1. Education and Manpower Development, 2000. No. 20.

Author

University of the Orange Free State, Bloemfontein (South Africa)., Strauss, J. P., van der Linde, H. J., and Plekker, S. J.

Abstract

This is the 20th publication in a series that provides an overview of various aspects of education in South Africa. As in the past, the purpose is to give a broad perspective on education in South Africa. Obtaining data remains a concern, as provinces still experience difficulties collecting and capturing data. Data show that the total number of learners in the system has decreased by 6%, a result of the entrance age policy of the government, fewer grade 12 failures returning to school, and possibly health-related reasons. The majority of learners in the educational system are still female. Of great concern is the number of under-qualified teachers, and addressing this need must be a priority with the national and provincial education departments. The matric (matriculation examination) results were better in 2000, and the national pass rate for the first time approached that of 1994 at 58%. The publication includes an overview of university and technikon (technical school) staff along with student enrollment data. Learner enrollment projections are made up to the year 2010. No official figure is available for HIV/AIDS cases, so this important variable is not included in projections. The final graph compares the results of grade 12 students at the end of 2000 with United Nations Monitoring of Learners' Achievement (MLA) and the Third International Mathematics and Science Study results. Data are supplied for nine provinces and, in some cases, additional divisions and the country as a whole. Data include the number of teachers and their qualifications, student enrollment for each province by grade and gender, matric test results by subject and province, and province, university, and technical school enrollment, and achievement data. (Contains 14 figures.) (SLD)

Published
2001

2. Education and Manpower Development, 1999. No. 19.

Author

University of the Orange Free State, Bloemfontein (South Africa)., Strauss, J. P., van der Linde, H. J., and Plekker, S. J.

Abstract

This is the 19th publication in a series that provides an overview of various aspects of education in South Africa. No publication was produced in 1999 because official data were not yet ready, so this document contains some 1998 information along with that for 1999. Obtaining data on a racial basis remains a problem, and it is recognized that the reaching of important goals of the national educational policy with respect to equity, redress, and access can only be achieved if educational data can be disaggregated in terms of racial groupings. In this report indicators other than matric results (matriculation examination) are presented for the first time with the report of South African results for two international studies. In 1999, the 2,772,225 students of the KwaZulu-Natal education department represented 22.5% of the country's total students. In contrast, only 1.7% (204,238) students were enrolled in the Northern Cape region. Data are supplied in graph and table form for the following provinces: (1) Western Cape; (2) Eastern Cape; (3) Free State; (4) Gauteng; (5) KwaZulu-Natal; (6) Mpumalanga; (7) Northern Cape; (8) Northern Province; and (9) North West. Data include the number of teachers and their qualifications, student enrollment for each province by grade and gender, matric test results by subject and province, university and technical school enrollment, and achievement data in numeracy and literacy. (Contains 14 figures.) (SLD)

Published
2000

3. Education and Manpower Development, 1997. No. 18.

Author

University of the Orange Free State, Bloemfontein (South Africa)., Strauss, J. P., van der Linde, H. J., Plekker, S. J., and Strauss, J. W. W.

Abstract

This eighteenth publication in the series provides a visual overview of various facts on education in South Africa. Up to 1995, educational data were presented by racially segregated education departments; now data are presented by the newly structured nonracial departments. The unavailability of data on a racial basis means that educational progress made by different population groups could not be measured. Information is also lacking on teacher education and teacher supply and development in various provinces. In 1997, 12,001,813 students were enrolled in South Africa's schools, with nearly 25% in the Kwaulu-Natal Education Department. About one-third of these students were in grades 1 to 3, the "Foundation Phase." Other phases are "Intermediate" (grades 4 to 6), "Senior" (grades 7 to 9), and "Further Education and Training" (grades 10 to 12). Learner enrollment is given according to gender and grade and enrollment projections are given for each of the provinces. Information is also supplied for university enrollment and faculty by racial population, and data are presented on aspects of educational finance, including expenditures per student for each province. (Contains 17 graphs.) (SLD)

Published
1998

4. Education and Manpower Development 1996. No. 17.

Author

University of the Orange Free State, Bloemfontein (South Africa)., Strauss, J. P., van der Linde, H. J., Plekker, S. J., and Strauss, J. W. W.

Abstract

This is the second publication in the series that provides information about education in the new South Africa. Educational data were collected by the new nonracial education departments in each of the nine provinces. Because of the difficulties of gathering information on the new systems, no evaluation of the educational progress made by disadvantaged groups is possible. A new Education Management Information System being developed will improve the gathering of information for subsequent volumes. A series of figures presents information about South Africa's 8,138,591 primary and 3,910,346 secondary students and their schools and teachers. The following figures are included: (1) "Learner Enrollment According to Province and School Phase, 1996"; (2) "Learner Enrollment According to School Phase and Gender, 1996"; (3) a 10-part figure of learner enrollment by region and for the whole country; (4) "Number of Educators and Learner Enrollment per Province, 1996"; (5) "Number of Schools and Learner Enrollment per Province, 1996"; (6) "Matric Results According to Province, 1994-1996"; (7) "Results for History, Mathematics and Physical Science in the Matriculation Examination, 1996"; (8) "Results for English and Biology in the Matriculation Examination, 1996"; (9) "Comparison between the Population and Learner Enrollment per Province, 1996"; (10) a 10-part figure with enrollment forecasts for each province and the whole country from 1997 to 2005; (11) "Students at Universities According to Population Group, 1996"; (12) "Number of Staff Members at Universities According to Population Group, 1996"; (13) "Students at Technikons According to Population Group, 1996"; and (14) "Number of Staff Members at Technikons According to Population Group, 1996." An appendix lists addresses of universities and university and teacher training college contact persons. (SLD)

Published
1997

17. Abstracts of papers and posters

Author

Anthonio, R. L., Willemsen, A. T. M., Visser, T., van Waarde, A., Elzinga, P., Weemaes, A., Meeder, J. G., Pruim, J., Visser, G., Blanksma, P. K., Vaalburg, W., Bloemen, P. G. M., Henricks, P. A. J., van Bloois, L., van den Tweel, M. C., Nijkamp, F. P., Crommelin, D. J. A., Storm, G., de Boer, A. H., Winter, H. M. I., Lerk, C. F., de Boer, J., Meurs, H., Bottone, A. E., Koopal, M., Visser, J. C., Zaagsma, J., Borger P., Kauffman H. F., Vijgen J. L. J., Postma D. S., Vellenga E., Buckley, Theresa L., Buikema, H., van Gilst, W. H., van Veldhuisen, D. J., de Smet, B. J. G. L., Scholtens, E., Lie, K. I., Wesseling, H., Cheung, P. K., Dijkhuis, F. W. D., Bakker, W. W., Visser, J., Coopes, R. P., Benthem, L., van der Leest, J., Roffel, A. F., Coppes, R. P., Zeilstra, L. J. W., Vissink, A., Konings, A. W. T., Dijkstra, M., Veld, G. In't, Müller, M., van den Berg, G. J., Kuipers, F., Vonk, R. J., Elsinga, P. H., Franssen, E. J. F., van der Graaf, W. T. A., de Vries, E. G. E., Visser, G. M., Vos, M. G., Braker, A. H., Visser, T. J., Visser, G. M., Engels, F., van Houwelingen, A. H., van de Velde, M. J., Gansevoort, R. T., Sluiter, W. J., Hemmelder, M. H., de Zeeuw, D., de Jong, P. E., Gelissen, H. P. M. M., Henning, R. H., Epema, A. H., van Eekeren, J., Hennis, P. J., Den Hertog, A., de Graaf, S. S. N., Kellie, S. J., Bloemhof, H., Johnston, I., Besser, M., Chaseling, R. W., Ouvrier, R. A., Uqes, D. R. A., De Haan, A., Geerligs, H. J., Huchshorn, J. P., Van Scharenburg, G. J. M., Wilschut, J., Haas, M., Kluppel, C. A., Meijer, D. K. F., Moolenaar, F., Heerdink, Eibert R., Leufkens, Hubert G., Herings, Ron M. C., Stricker, Bruno H. Ch., Bakker, Albert, Heesen W. F., Beltman F. W., Smit A. J., May J. F., Meyboom-de Jong B., Duin, M., van den Akker, J., te Pas, M. F. W., van Popta, J. P., Nelemans, S. A., van der Linde, H. J., de Boer, A., Sturmans, F., Hessel, E. M., Van Oosterhout, A. J. M., Hofstra, C. L., Garssen, J., van Loveren, H., Savelkoul, H. F. J., Hoekstra, Y., Weersink, E. J. M., de Jong, J. W., van der Belt-Gritter, B., Jonkman, Lisa M., Kemner, Chantal, Koelega, Harry S., van Engeland, Herman, Verbaten, Marinus N., Kalivianakis, M., Zijlstra, I., Verkade, H. J., Elzinga, H., Stellaard, F., Kamps, J. A. A. M., Swart, P. J., Morselt, H., Scherphof, G. L., Kenemans, J. L., Lorist, M. M., Koopen, N. R., Kraneveld, A. D., Koster, A. Si., Kuipers, M. E., Groenink, M., Huisman, H., Schuitemaker, H., Lau, H. S., van den Broek, I. J. P. M., van Dijk, A., Oostinga, J., Porsius, A. J., Lin, Y., Havinga, R., Meijer, R. J., van der Mark, Th. W., Koëter, G. H., Michels, A. A., Nguyen, V. -T., Bensaude, O., Kampinga, H. H., Mohede, Inge C. M., Van Antoon J. M., Molema, Grietje, Edgington, Thomas S., Thorpe, Philip E., Olinga, P., Sandker, G. W., Slooff, M. J. H., Merema, M. T., Groothuis, G. M. M., Hofman, G., Van Ark, I., Paulussen, J. J. C., Fischer, M. J. E., de Mol, N. J., Janssen, L. H. M., Peters, E. Th. J., van der Werf, G. Th., Haaijer-Ruskamp, F. M., Pinto, Yigal M., Rooks, Gerrit, Grandjean, Jean G., Ebels, Tjark, Schunkert, H., Redegeld, Frank A., Garssen, Johan, van Loveren, Henk, Rigter, Irma M., van Groningen, Muck, Boks, Gertjan J., Tollenaere, Jan P., Trollope, Keith I., Vinter, Jeremy G., Hashjin, Gudarz Sadeghi, Folkerts, Gert, van de Loo, Peet G. F., Santing, R. E., Olymulder, C. G., van der Molen, K., Pasman, Y., Scheerens, Heleen, Van Loveren, Henk, Seppenwoolde-Waasdorp, T. J. A., de Boer, P., Van Engelen, H. M. J., Thijssen, J. H. H., Maes, R. A. A., Smit, J., Smit, J. W., Steen, H., Steurs, M. H., Kuks, P. F. M., Leusink, J. A., Szabó, Balázs M., Crijns, Harry J. G. M., Wiesfeld, Ans C. P., Talsma, H., Borchert, J. C. H., van Steenbergen, M. J., Hennink, W. E., Teeuw, K. B., Cromheecke, H., Schreudering, A., Teisman, B. C. H., Maselbas, W., Wolters-Keulemans, G. T. P., Tieleman, R. G., de Langen, C. D. J., Bel, K., Crijns, H. J. G. M., Grandjean, J., Wijffels, M., Klimp, A. H., van de Meer, P. F., Allessie, M. A., van Patot, H. A. Tissot, de Jongh, B. M., Tuininga, Y. S., Brouwer, J., Haaksma, J., Man in't Veld, A. J., Blomjous, F. J., Vingerhoeds, M. H., Belliot, S. O., Haisma, H. J., Visscher, C. A., Huisman, R. M., Navis, G. J., de Vlieger, J. F., van den Wijngaard, P., Wilting, J., van Heuven-Nolsen, D., Voors, A. A., van Brussel, B. L., Plokker, H. W. M., Van Waardenburg R. C. A. M., Meijer, Prins J., De Vries, C., Mulder N. H., Wierenga, P. K., Wilschut J., Schoen P., and Bron R.

Published
1994
Full Text
View/download PDF

24. Varying cecal bacterial loads influences colitis and gastritis in HLA-B27 transgenic rats

Author

Wilson, K. H., Balfour Sartor, R., Ikeda, J. S., Linde, H. J., Scholmerich, J., and Rath, H. C.

Subjects
digestive system
Abstract

Background & Aims: Recent data support an important role of resident luminal bacteria in experimental colitis. We determined how altered cecal bacterial loads influence colitis and gastritis. Methods: A cecal self-filling blind loop (SFBL) was created or the cecum was excluded from the fecal stream in specific pathogen–free HLA-B27 transgenic (TG) rats with early colitis and in nontransgenic (nonTG) littermates; controls underwent sham operation (SHAM). Luminal bacterial concentrations were determined by culture and counting chamber. Results: TG rats with SFBL had more severe cecal inflammation and leukocytosis than TG SHAM controls. TG excluded rats with low cecal bacterial loads had no cecal inflammation and less colitis and gastritis than SHAM controls, despite having normal distal colonic and gastric bacterial concentrations. Metronidazole attenuated cecal inflammation and eliminated Bacteroides in SFBL TG rats. NonTG SFBL rats had mild cecal inflammation and no gastritis and colitis. The ratio of total anaerobic to aerobic bacteria was 1000-fold greater in SFBL than in SHAM rats, with a 10,000-fold increased ratio of Bacteroides spp. to aerobes. Conclusions: The luminal bacterial load and composition determines the activity of cecal inflammation in genetically susceptible hosts. Lowering cecal bacterial concentrations can diminish inflammation in remote organs.GASTROENTEROLOGY 1999;116:310-319

Published
1999
Full Text
View/download PDF

25. The Electro-Mechanical window: a risk marker for Torsade de Pointes in a canine model of drug induced arrhythmias.

Author

van der Linde, HJ, Van Deuren, B, Somers, Y, Loenders, B, Towart, R, Gallacher, DJ, van der Linde, H J, and Gallacher, D J

Subjects
BIOMARKERS, VENTRICULAR tachycardia, LABORATORY dogs, CARDIOVASCULAR pharmacology, DRUG side effects, ARRHYTHMIA, LEFT heart ventricle, ADRENERGIC beta agonists, MYOCARDIAL depressants, BODY temperature, CLINICAL drug trials, ANIMAL experimentation, ISOPROTERENOL, HEART, ATROPINE, LONG QT syndrome, CARDIAC contraction, ELECTROCARDIOGRAPHY, HEART physiology, DRUG development, DOGS, PHARMACODYNAMICS
Abstract

Background and Purpose: In cardiovascular pharmacology, electrical and mechanical events can be distinguished, and the phrase 'electro-mechanical window' (EMw) describes the temporal difference between these events. We studied whether changes in EMw have potential predictive value for the occurrence of arrhythmias in fentanyl/etomidate-anaesthetized beagle (FEAB) dogs.Experimental Approach: The EMw was calculated as differences between the QT interval and QLVP(end) in FEAB dogs during atrial pacing, treatment with isoprenaline or atropine, body temperature changes and induction of Torsade de Pointes (TdP) in an LQT1 model.Key Results: The electrical systole (QT interval) was shorter than the duration of the mechanical event (QLVP(end) ), providing a positive EMw. Atrial pacing, atropine or body temperature changes had no major effects on EMw, despite large changes in QT duration. However, β-adrenoceptor stimulation (with isoprenaline) decreased the EMw (from 90 to 5 ms) and in combination with HMR1556, a blocker of the slowly activating potassium current (I(Ks) ), induced a large negative EMw (-109ms) and TdP. Prevention of TdP by atenolol or verapamil was associated with a less negative EMw (-23 to -16ms). Mexiletine, a poorly effective long QT treatment, did not affect the EMw or prevent TdP induction.Conclusions and Implications: The EMw is a marker, other than QT prolongation, of TdP risk in the FEAB model. Therefore, we suggest examining the EMw as a risk marker in cardiovascular safety studies and as a potential biomarker to improve clinical management of long QT syndrome patients, especially in patients with borderline QT prolongation. [ABSTRACT FROM AUTHOR]

Published
2010
Full Text
View/download PDF

26. Management of a large healthcare-associated outbreak of Panton–Valentine leucocidin-positive meticillin-resistant Staphylococcus aureus in Germany.

Author

Wagenlehner, F.M.E., Naber, K.G., Bambl, E., Raab, U., Wagenlehner, C., Kahlau, D., Höller, C., Witte, W., Weidner, W., Lehn, N., Harbarth, S., and Linde, H.-J.

Abstract

Summary: We report the largest documented healthcare-associated outbreak of Panton–Valentine leucocidin-positive meticillin-resistant Staphylococcus aureus (PVL+ MRSA) in Europe. Six index patients from three long-term care facilities (LTCFs) were screened positive for PVL+ MRSA in 2004 on admission to a community hospital in Germany. The purpose of this prospective study was to describe the prevalence of PVL+ MRSA in the LTCFs before and after infection control interventions. Screening for MRSA with or without PVL was performed in all three LTCFs in 2004 [453 residents, 240 healthcare workers (HCWs)] and 2005 (440 residents, 192 HCWs). Swabs from anterior nares and wounds, if applicable, were collected. Colonised residents and staff were treated with mupirocin nasal ointment and topical antiseptics, and staff were provided with hygiene education. Total MRSA carrier rate of residents and HCWs in 2004 was 11.3% (PVL+ MRSA 9.1%, PVL− MRSA 2.2%). There were comparable carrier rates between residents and HCWs in each LTCF. All PVL+ MRSA isolates were of clonal origin (MLST 22) representing a novel spa sequence type t310. A decrease in total MRSA prevalence (from 11.3 to 5.5%) and PVL+ MRSA (from 9.1 to 3.3%) was observed in 2005. The rate of PVL− MRSA remained unaffected. No symptomatic skin infections were noted among residents or HCWs. In this outbreak incomplete control of PVL+ MRSA presumably resulted from difficult and delayed detection and decolonisation of carriers, incomplete compliance with control measures and lack of enforcement by public health authorities. [Copyright &y& Elsevier]

Published
2007
Full Text
View/download PDF

27. Emergence of methicillin-resistantStaphylococcus aureuswith Panton-Valentine leukocidin genes in central Europe.

Author

Witte, W., Braulke, C., Cuny, C., Strommenger, B., Werner, G., Heuck, D., Jappe, U., Wendt, C., Linde, H.-J., and Harmsen, D.

Subjects
STAPHYLOCOCCUS aureus infections, METHICILLIN resistance, DRUG resistance in microorganisms, METHICILLIN, STAPHYLOCOCCAL diseases, PENICILLIN, BACTERIAL diseases, POLYMERASE chain reaction
Abstract

The aim of the present study was to investigate strains of methicillin-resistantStaphylococcus aureus(MRSA) for the presence of thelukS-lukF determinant of Panton-Valentine leukocidin and to further characterize strains found to contain the genes. During the past 2 years, MRSA containing thelukS-lukF genes for Panton-Valentine leukocidin, particularly those emerging outside of hospitals, have become of interest. MRSA strains sent to the national reference center in Germany were investigated forlukS-lukF by polymerase chain reaction (PCR). If the presence oflukS-lukF was demonstrated, strains were further characterized by molecular typing (determination ofSmaI pattern,spasequence, and multilocus sequence type), PCR demonstration of resistance genes, and characterization of the SCCmecelement. Since the end of 2002, MRSA containing Panton-Valentine leukocidin genes have been demonstrated as the causative agent of 28 cases of infection (9 community-acquired cases, 19 sporadic nosocomial cases) in different areas of Germany. Twenty-seven of these 28 isolates exhibited a unique pattern of genomic typing: all exhibited multilocus sequence type 80,spasequence type 44, and aSmaI macrorestriction pattern that corresponds to a community-acquired strain of MRSA from France and Switzerland. In addition to resistance to oxacillin, the strains exhibited resistance to ciprofloxacin, tetracycline (tetM), and fusidic acid, the last of which is encoded by thefar-1 gene. Thefar-1 gene was shown to be located on the plasmid. One isolate corresponded to community MRSA (cMRSA) of multilocus sequence type 1 from the USA. [ABSTRACT FROM AUTHOR]

Published
2005
Full Text
View/download PDF

28. Lack of evidence for persistent nasal colonization with community-acquired methicillin-resistant Staphylococcus aureus in a central European cohort.

Author

Hanses, F., Huetz, T., Reischl, U., Ehrenstein, B. P., Linde, H.-J., and Salzberger, B.

Subjects
STAPHYLOCOCCUS aureus infections, SOFT tissue infections, NASAL manifestations of general diseases, STAPHYLOCOCCUS aureus, PATIENTS, DIAGNOSIS
Abstract

One hundred and three patients who had previously tested positive for community-acquired methicillin-resistant Staphylococcus aureus (cMRSA) were followed up for a mean time of 32.6 months. Eighty patients had a history of skin or soft tissue infection, and the remainder were mostly asymptomatic carriers. Of 103 patients, only two reported ongoing symptoms with abscess formation. Of 81 nasal swabs available, 30.9% were positive for S. aureus but only four yielded Panton-Valentine leukocidin- positive methicillin-resistant S. aureus. In summary, we were unable to find persistent health issues or nasal colonization with cMRSA in a cohort of previously cMRSA-infected/colonized patients. [ABSTRACT FROM AUTHOR]

Published
2015
Full Text
View/download PDF

29. Powerful and Structured Innovation using Contradictions for Gaining Orientation.

Author

Linde, H. J., Hall, D. M., and Herr, G. H.

Subjects
*CREATIVE ability, *TECHNOLOGICAL innovations, *INVENTIONS
Abstract

An increasing number of tools and techniques are available for improved performance in creativity, invention and innovation. These tools and techniques address specific problem areas such as identification of customer need, identification of creative potential solutions and marketing concepts. WOIS is a strategy which combines these tools in order to enhance the effectiveness of problem-solvers' daily work by structuring the innovation process into three stages, covering the development procedure from 'problem identification' right through to 'innovative solution concept'. It is currently in use to great effect in a number of industries. The key to the effectiveness of WOIS is to allow the contradicting development factors to contribute to a novel and innovative solution to the problem. This differs from the commonly taken approach, which consists of formulating the most suitable 'trade-off' to best suit customers' requirements. This paper describes the first stage of WOIS and gives an introduction to the further steps which result in the definition of an innovative solution concept. [ABSTRACT FROM AUTHOR]

Published
1999
Full Text
View/download PDF

42. 05. The electro-mechanical window as Torsade de Pointes risk marker in conscious and anaesthetised dogs after IKS blockade.

Author

van der Linde, H. J., Cools, F., Vanlommel, A., Janssens, S., Verrelst, J., Van Deuren, B., Somers, Y., Teisman, A., Towart, R., and Gallacher, D. J.

Subjects
*BIOMARKERS, *DOGS, *ANESTHESIA, *ANIMAL anesthesia, *DOMESTIC animals
Abstract

The electro-mechanical window (EMw) is a recently proposed biomarker describing the temporal difference between electrical and mechanical events in beating hearts and is a precursor to identify Torsade de Pointes (TdP) risk in the anaesthetised dog. In follow-up studies, conscious dogs (n=6; telemetered) showed comparable baseline values to anaesthetised dogs (n=20): QT=250 vs 252⇔…ms, QLVPend=347 vs 339⇔…ms and EMw=+96 vs +87⇔…ms, respectively. To compare the EMw in conscious and anaesthetised dogs after IKs blockade. Six conscious dogs were orally treated with JNJ303 (20⇔…mg/kg) and four anaesthetised dogs received infusions of JNJ303 (cumulative 2.5⇔…mg/kg). In both conditions JNJ303 induced QT prolongation, a large negative EMw and TdP appeared in 50% of the dogs in each condition (pause-dependent and adrenergic-dependent). In the conscious dogs significant differences in maximum plasma levels (PL), QT and EMw were observed between dogs that induced TdP and those without TdP: PL (4950 vs 1473⇔…ng/ml), QT (427 vs 351⇔…ms) and EMw (⇔'150 vs ⇔'68⇔…ms), without differences in RR (642 vs 654⇔…ms) and QLVPend (273 vs 287⇔…ms), respectively. Also in anaesthetised dogs long QT (766⇔…ms) and large negative EMw (⇔'445⇔…ms) at similar PL (5743⇔…ng/ml) were observed. In conclusion a potent IKs blocker (JNJ303) can cause TdP in conscious and anaesthetised dogs, coupled with a large negative EMw. [ABSTRACT FROM AUTHOR]

Published
2011
Full Text
View/download PDF

44. EEG in the FEAB model: measurement of electroencephalographical burst suppression and seizure liability in safety pharmacology.

Author

van der Linde HJ, Van Deuren B, Somers Y, Teisman A, Drinkenburg WH, and Gallacher DJ

Subjects
Anesthetics, Intravenous administration & dosage, Animals, Bicuculline pharmacology, Central Nervous System drug effects, Dogs, Etomidate administration & dosage, Female, Fentanyl administration & dosage, Male, Models, Animal, Pentylenetetrazole pharmacology, Toxicity Tests, Anesthesia, Convulsants pharmacology, Electroencephalography methods, Seizures chemically induced
Abstract

Introduction: The purpose of this study was to explore the integration of electroencephalographical (EEG) measurements into the fentanyl/etomidate-anaesthetised Beagle (FEAB) model in order to detect burst suppression and/or seizure development caused by compounds, prior to new molecular entity (NME) declaration. Detecting such unfavourable side effects prevents their being found in conscious animals at a later stage of safety evaluation. In addition, this has the advantage of performing safety studies on the three vital organ systems (cardiovascular system, respiratory system and central nervous system) within one and the same animal model., Methods: Dogs were anaesthetized and instrumented according to the FEAB model requirements, and in addition three needle electrodes were placed on the cranium and a one lead EEG signal was measured. The raw signal was analysed by the Narcotrend® (MonitorTechnik, Bad Bramstedt, Germany) for depth of anaesthesia registration, visually analysed for burst suppression ratio calculation after different anaesthetics (pentobarbital and etomidate), and spiking and seizure activity were quantified after intravenous administration of different proconvulsant agents: pentylenetetrazole (PTZ), bicuculline (BCC), bupropion (BUP) and pilocarpine (PIL)., Results: High doses of pentobarbital (60 mg/kg over 10 min) and etomidate (6 mg/kg over 10 min) induced dose-dependent burst suppression of 98 ± 2% and 61 ± 16%, respectively. Infusions of PTZ (1.5mg/kg/min), BCC (0.0625 mg/kg/min), BUP (0.5mg/kg/min) and PIL (5mg/kg/min) induced dose-dependent spiking and seizures: the thresholds were 34 ± 2, 0.15 ± 0.03, 10.0 ± 1 and 144 ± 9 mg/kg, respectively. In PTZ-treated dogs, spiking and seizures could be abolished with diazepam (2mg/kg i.v.) or with propofol (4 mg/kg i.v.)., Discussion: The present study showed that a one lead EEG can be used reliably in the FEAB model to estimate the depth of anaesthesia, and to detect burst suppression and seizure risk in safety pharmacology studies., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Published
2011
Full Text
View/download PDF

45. Single-nucleotide polymorphism in the SCCmec-orfX junction distinguishes between livestock-associated MRSA CC398 and human epidemic MRSA strains.

Author

Reischl U, Frick J, Hoermansdorfer S, Melzl H, Bollwein M, Linde HJ, Becker K, Köck R, Tuschak C, Busch U, and Sing A

Subjects
Animals, Germany, Humans, Species Specificity, Animals, Domestic microbiology, Disease Outbreaks, Methicillin-Resistant Staphylococcus aureus genetics, Methicillin-Resistant Staphylococcus aureus isolation & purification, Polymorphism, Single Nucleotide genetics, Staphylococcal Infections epidemiology, Staphylococcal Infections microbiology
Abstract

A number of real-time PCR assays for direct detection of methicillinresistant (MRSA) in clinical specimens are targeting staphylococcal cassette chromosome mec (SCCmec) right extremity sequences and the S. aureus chromosomal orfX gene sequences located to the right of the SCCmec integration site. When testing 184 MRSA strains of human and animal origin from geographically distinct locations, we identified several characteristic single-nucleotide polymorphisms (SNPs) within the SCCmec-orfX junction of livestock-associated (LA) MRSA CC398 which serve as suitable strain markers for screening purposes. Within an assay time of 60 minutes and an additional 10 minutes for the melting curve analysis, all MRSA CC398 isolates were correctly identified by their characteristic T(m) value in the commercial LightCycler MRSA Advanced test. Studies to confirm the diagnostic accuracy of the SNP-based strain identification assay with a larger collection of clinical and LA-MRSA strains are ongoing.

Published
2009

46. Calcium sensors as new therapeutic targets for airway hyperresponsiveness and asthma.

Author

Ten Broeke R, Folkerts G, Leusink-Muis T, Van der Linde HJ, Villain M, Manion MK, De Clerck F, Blalock JE, and Nijkamp FP

Subjects
Acetylcholine pharmacology, Animals, Bradykinin pharmacology, Calcium Channels physiology, Epithelium physiology, Guinea Pigs, Histamine administration & dosage, Histamine pharmacology, Intercellular Signaling Peptides and Proteins, Muscle Contraction drug effects, Nitric Oxide metabolism, Trachea drug effects, Trachea physiology, Asthma drug therapy, Calcium physiology, Carrier Proteins pharmacology, Oligopeptides pharmacology, Peptides
Published
2001
Full Text
View/download PDF

47. Factors that determine acetylcholine responsiveness of guinea pig tracheal tubes.

Author

Folkerts G, Kloek J, Geppetti P, Van der Linde HJ, and Nijkamp FP

Subjects
Acetylcholinesterase drug effects, Acetylcholinesterase metabolism, Animals, Atropine pharmacology, Cholinesterase Inhibitors pharmacology, Dose-Response Relationship, Drug, Enzyme Inhibitors pharmacology, Epithelium physiology, Guinea Pigs, In Vitro Techniques, Male, NG-Nitroarginine Methyl Ester pharmacology, Nitric Oxide Synthase antagonists & inhibitors, Physostigmine pharmacology, Specific Pathogen-Free Organisms, Trachea physiology, Acetylcholine pharmacology, Muscle Contraction drug effects, Trachea drug effects, Vasodilator Agents pharmacology
Abstract

Acetylcholine administered to the inside of epithelium-denuded tracheal tubes did cause a potent contraction (2486+/-120 mg). In contrast, a response was hardly observed in tissues with an intact epithelial layer (674+/-81 mg), which was due to both the synthesis of nitric oxide and the activity of acetylcholinesterase, since the contractions to acetylcholine were significantly enhanced after preincubation with N(omega)-nitro-L-arginine methyl ester (L-NAME) or physostigmine (1374+/-65 and 1120+/-65 mg, respectively). In addition, the suppressive effect was caused by the barrier function of the epithelial layer, since preincubation of epithelium-denuded tissues with physostigmine significantly increased the pD2 value for acetylcholine (7.48+/-0.04) compared to intact tissues preincubated with physostigmine (6.32+/-0.10) and epithelium-denuded preparations without physostigmine (6.37+/-0.06). Increasing concentrations of physostigmine administered to the inside of tissues with epithelium did induce a potent spontaneous contraction (1440+/-350 mg) that was prevented by atropine. In contrast to what was expected, the contractile response was diminished in tracheal tubes without epithelium (665+/-221 mg). It is concluded that contractions of epithelium-denuded tissues are more pronounced to exogenous than to endogenous acetylcholine, and that the production and breakdown of this neurotransmitter is very rapid in intact guinea pig airways. Moreover, the release of nitric oxide and the barrier function of the epithelium did suppress the responsiveness to acetylcholine.

Published
2001
Full Text
View/download PDF

48. In vitro activities of six quinolones and mechanisms of resistance in Staphylococcus aureus and coagulase-negative staphylococci.

Author

Linde HJ, Schmidt M, Fuchs E, Reischl U, Niller HH, and Lehn N

Subjects
4-Quinolones, Coagulase analysis, Drug Resistance, Microbial genetics, Humans, Microbial Sensitivity Tests, Mutation, Staphylococcus aureus drug effects, Anti-Infective Agents pharmacology, DNA Topoisomerases, Type I genetics, Staphylococcus aureus genetics
Abstract

Of 94 clinical isolates of Staphylococcus aureus (n = 51) and coagulase-negative staphylococci (CNS) (n = 43), mutations in the quinolone resistance-determining region of topoisomerases GrlA, GrlB, GyrA, and GyrB together with MICs of six quinolones were analyzed. Amino acid substitutions at identical residues (GrlA residues 80 and 84; GyrA residues 84 and 88) were found in S. aureus and CNS. Active efflux, as suggested by blocking by reserpine, contributed substantially to the resistance phenotype in some strains. Among ciprofloxacin, clinafloxacin, levofloxacin, nalidixic acid, trovafloxacin, and sparfloxacin, a 0.5-microg/ml concentration of sparfloxacin discriminated best between strains with two or three mutations and those with no mutations.

Published
2001
Full Text
View/download PDF

49. Different subsets of enteric bacteria induce and perpetuate experimental colitis in rats and mice.

Author

Rath HC, Schultz M, Freitag R, Dieleman LA, Li F, Linde HJ, Schölmerich J, and Sartor RB

Subjects
Animals, Bacteroides isolation & purification, Ciprofloxacin pharmacology, Colitis drug therapy, Enterobacteriaceae drug effects, Female, HLA-B27 Antigen physiology, Imipenem pharmacology, Interleukin-1 analysis, Metronidazole pharmacology, Mice, Mice, Inbred BALB C, Rats, Rats, Inbred F344, Vancomycin pharmacology, Colitis microbiology, Enterobacteriaceae physiology
Abstract

Resident bacteria are incriminated in the pathogenesis of experimental colitis and inflammatory bowel diseases. We investigated the relative roles of various enteric bacteria populations in the induction and perpetuation of experimental colitis. HLA-B27 transgenic rats received antibiotics (ciprofloxacin, metronidazole, or vancomycin-imipenem) in drinking water or water alone in either prevention or treatment protocols. Mice were treated similarly with metronidazole or vancomycin-imipenem before or after receiving 5% dextran sodium sulfate (DSS). Germfree transgenic rats were colonized with specific-pathogen-free enteric bacteria grown overnight either in anaerobic or aerobic atmospheres. Nontransgenic rats colonized with anaerobic bacteria served as negative controls. Although preventive metronidazole significantly attenuated colitis in transgenic rats and DSS-treated mice, it had no therapeutic benefit once colitis was established. Ciprofloxacin also partially prevented but did not treat colitis in B27 transgenic rats. In both animal models vancomycin-imipenem most effectively prevented and treated colitis. Germfree transgenic rats reconstituted with enteric bacteria grown under anaerobic conditions had more aggressive colitis than those associated with aerobic bacteria. These results suggest that a subset of resident luminal bacteria induces colitis, but that a complex interaction of commensal aerobic and anaerobic bacteria provides the constant antigenic drive for chronic immune-mediated colonic inflammation.

Published
2001
Full Text
View/download PDF

50. In vivo increase in resistance to ciprofloxacin in Escherichia coli associated with deletion of the C-terminal part of MarR.

Author

Linde HJ, Notka F, Metz M, Kochanowski B, Heisig P, and Lehn N

Subjects
Bacterial Proteins physiology, Drug Resistance, Microbial genetics, Drug Resistance, Microbial physiology, Electrophoresis, Gel, Pulsed-Field, Escherichia coli genetics, Escherichia coli metabolism, Gene Deletion, Humans, Repressor Proteins physiology, Anti-Infective Agents pharmacology, Bacterial Proteins genetics, Ciprofloxacin pharmacology, Escherichia coli drug effects, Escherichia coli Proteins, Repressor Proteins genetics
Abstract

We recovered two isolates (EP1 and EP2) of Escherichia coli from the same patient that had identical pulsed-field gel electrophoresis patterns but required different MICs of ciprofloxacin (CIP): 16 and 256 mg/liter for EP1 and EP2, respectively. Both isolates had mutations in the quinolone resistance-determining regions of GyrA (Ser83Leu and Asp87Tyr) and ParC (Ser80Ile), but not in those regions of GyrB or ParE. Isolate EP2 was also more resistant to chloramphenicol, tetracyclines, cefuroxime, and organic solvents. A deletion of adenine (A) 1821 was found in marR of isolate EP2, which resulted in an 18-amino-acid C-terminal deletion in the MarR protein. The causative relationship between DeltaA1821 and the Mar phenotype was demonstrated both by the replacement of the wild-type marR by marR DeltaA1821 in isolate EP1 and by complementation with the wild-type marR in trans in isolate EP2. In isolate EP2 complemented with wild-type marR, susceptibility to chloramphenicol was restored completely, whereas susceptibility to CIP was restored only incompletely. Northern blotting demonstrated increased expression of marA and acrAB but not of soxS in isolate EP2 compared to EP1. In conclusion, the deletion of A1821 in marR in the clinical isolate EP2 caused an increase in the MICs of CIP and unrelated antibiotics. Presumably, the C-terminal part of MarR is necessary for proper repressor function.

Published
2000
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results