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1.
Article in German | MEDLINE | ID: mdl-39164394

ABSTRACT

BACKGROUND: Health promotion (HP) is a complex, politically required task. The quality of implementation correlates with the effectiveness of health promotion initiatives. Successful implementation requires consideration of contextual conditions, which tend to be neglected in effectiveness studies. The aim is to identify success factors and obstacles to the implementation of HP in daycare centers and elementary schools based on 4 projects (Fit fürs Leben, fit für pisa +, Buchprojekt Sonnige Traurigtage, and The Daily Mile) in the Göttingen/South Lower Saxony region. The effects of the COVID-19 pandemic are assumed to be relevant for the implementation of these projects. METHODS: In 24 semi-structured interviews and 2 focus group discussions between August 2021 and March 2022, practitioners were asked about the implementation of the four projects in their areas of activity. After transcription, the interviews were analyzed using qualitative content analysis. The Consolidated Framework for Implementation Research supported the analysis. RESULTS: A total of 22 groups of factors were identified, on the basis of which 22 recommendations for action for GF implementation were formulated. Success factors at the individual and intervention level were at the forefront. The COVID-19 pandemic had a positive impact on the importance of HP, even though its feasibility was hampered. DISCUSSION: Numerous findings on the implementation of HP in children's living environments were confirmed by the study. The high significance of the individual factors is striking, which could be due to the survey of interviewees being familiar with the projects. The study results contribute to the further development of implementation strategies in HP.


Subject(s)
COVID-19 , Child Day Care Centers , Health Promotion , SARS-CoV-2 , Child Day Care Centers/organization & administration , Health Promotion/organization & administration , Health Promotion/methods , Humans , COVID-19/prevention & control , COVID-19/epidemiology , Germany , Child , Pandemics/prevention & control , Child, Preschool , Schools/organization & administration , School Health Services/organization & administration , Focus Groups
2.
Gesundheitswesen ; 86(7): 499-507, 2024 Jul.
Article in German | MEDLINE | ID: mdl-38648854

ABSTRACT

BACKGROUND: International and national frameworks and initiatives call for strengthening the training of health professionals in the public health service (PHS) through cooperation with universities. The German Medical Licensing Regulations of 21st Sep 2021 provides for an integration of PHS into undergraduate medical training in the final year since 1st May 2022. The present study presents the procedure and results of the final year elective Public Health (PH) implementation for medical students at the University Medical Center Göttingen (UMG) in cooperation with the local PHS. METHODS: In the twelve-month project UNITE (07/21-06/22), the final year elective PH was implemented in seven steps: analysis of the framework conditions, conception of the elective, preparation of a logbook, pilot phase with five students in one-week rotations, public relations for students, introduction of a medical didactic training for staff of the health department and implementation of the elective PHS with students. RESULTS: A cooperation agreement between UMG and the Health Department regulates the training of medical students. Students complete four-week rotations in the areas of public health service and funeral services, paediatric and adolescent medical service, infection control and social psychiatric service. The logbook for students contains learning objectives for individuals specialised in services for self-assessment of the acquired competences. The didactics training was implemented with high learning success of the participating staff. So far three final year students have successfully completed the elective. CONCLUSIONS: The implementation of final year elective PHS strengthens the anchoring of public health topics in the education of medical students in Göttingen and makes PHS more visible as a professional perspective. Essential for the successful implementation were the establishment of a continuous cooperation between the university and the health department, student-oriented teaching-learning concept with a logbook suitable for the location, a trained multiprofessional team in the health department, and the evaluation of the elective for quality assurance and further development of the training. The concept presented here can help other locations in establishing the final year elective in PH and can be adapted to specific local conditions.


Subject(s)
Curriculum , Education, Medical, Undergraduate , Public Health , Germany , Public Health/education , Academic Medical Centers/organization & administration , Students, Medical/statistics & numerical data , Humans
3.
Nervenarzt ; 94(11): 1034-1042, 2023 Nov.
Article in German | MEDLINE | ID: mdl-37796324

ABSTRACT

BACKGROUND: Early information and support in dementia (FIDEM) is a cross-sectoral, general practitioner-centered network model for the improvement of community-based care of people with dementia and their caregivers by systematically assigning them to non-physician healthcare providers. OBJECTIVE: To describe the implementation of FIDEM in Göttingen, Germany and to exploratorily evaluate satisfaction and relief vs. additional workload. MATERIAL AND METHODS: FIDEM was established in Göttingen in 2017. Community-based and district-based networks consisted of medical (general practitioners) and non-medical cooperation partners (occupational therapists, care counselling, other non-medical care providers) and were instructed to efficiently share information. During biannual network meetings from August 2017 to October 2019, a self-developed questionnaire for quality management and evaluation of the aspects of the project described above was filled out by participants attending the meetings. RESULTS: Consecutive recruitment resulted in 7 networks by October 2019, with participation of 29 general practitioners and 46 non-medical care providers, serving as cooperation partners. Quantitative evaluation of 80 FIDEM cooperation partners revealed high satisfaction ratings with all aspects of the model (M from 7.22 to 7.87 out of possible "10"), with partially higher ratings on the part of primary care physicians. Furthermore, all participants reported a reduction in workload due to participation, which was significantly higher for primary care physicians across all scales (all p-values < 0.001). CONCLUSION: FIDEM has been implemented in Göttingen beyond a funded pilot project phase. High satisfaction ratings and considerable relief in workload suggest the continuation of FIDEM along with a full evaluation and, provided positive results, its consolidation of and transfer to other regions in Germany.


Subject(s)
Dementia , General Practitioners , Humans , Workload , Pilot Projects , Dementia/diagnosis , Dementia/therapy , Personal Satisfaction , Germany
4.
Gesundheitswesen ; 85(3): 203-208, 2023 Mar.
Article in German | MEDLINE | ID: mdl-34560803

ABSTRACT

General practitioners play a major role in the health care of the population. Only a small proportion of patients receives care from specialised consultants, in a hospital or in a university hospital. Most of the patients consult a general practitioner. The strengthening of general practice that is called for in the Master Plan for Medical Studies 2020 in new state examination formats, for instance, means that this central position in patient care will be reflected in studies and examinations in the future. The general medical setting is subject to a specific background with unselected patients and a hermeneutic understanding of cases. The format of the new final examination promotes general medical and interdisciplinary competencies in medical interviewing, physical examination, dealing with diseases that can be treated on an outpatient basis, prevention, and the application of general medical guidelines of ethics and law. The standardised oral-practical examination has newly been designed by the Institute for Medical and Pharmaceutical Examination Questions (IMPP). It includes real patients in an outpatient setting. In eight steps, it integrates communicative and technical examination aspects. Two trained examiners will observe and assess the performance of graduates using standardised evaluation forms. The new examination format was developed in 2019 by the IMPP and faculty from various medical schools, was tested in five general medical teaching practices, revised, and then piloted in fourteen examinations. Standardised specifications for the examination process, spatial equipment, and examiner training were developed by IMPP. With approximately 10,000 examinees per year and two students per examination day, a total of 5,000 examination days will be required in general practices. The expertise of the German College of General Practicioners and Family Physicians (DEGAM), the Society of University Teachers of General Medicine (GHA), and the university locations, together with the great potential as the largest specialist group in Germany suggest that the goal of recruiting and motivation of practices appears achievable. With regard to funding, political decisions are necessary. In an increasingly complex care system, the redesign of the oral-practical examination in the outpatient setting contributes to strengthening interdisciplinary and multi-professional cooperation.


Subject(s)
Curriculum , General Practice , Humans , Germany , General Practice/education , Family Practice/education , Physical Examination
5.
Gesundheitswesen ; 83(S 02): S130-S138, 2021 Nov.
Article in German | MEDLINE | ID: mdl-34852383

ABSTRACT

Objectives It is difficult to obtain longitudinal 'real world' data from ambulatory medical care in Germany in a systematic way. Our vision is a large German research data repository featuring representative, anonymized patient and outpatient health care data, longitudinal, continuously updated and across different providers, offering a perspective of linking secondary care data or additional data obtained from research cohorts, for example patient reported data or biodata, and will be accessible for other researchers. Here we report specific methods and results from the RADAR project.Methods Survey of legislation, design of technical processes and organisational solutions, with a feasibility study to evaluate technical and content functionality, acceptability and performance fitness for health services research questions.Results In 2016, a multi-disciplinary scientific team initiated the development of a privacy protection and IT security concept for data exported from the electronic medical records (EMR) of physicians' practices in line with the European General Data Protection Regulation. Technical and organisational requirements for lawful research infrastructure were developed and executed for use in a specific case, namely ̒oral anticoagulation'. In 7 Lower Saxonian general practices, 100 patients were selected by their physician and their data - reduced to 40 essential data fields - extracted from EMR via a mandatory software interface after informed consent. Still in the practice, the data were split into identifying or medical data. These were encrypted and transferred either to a trusted third party (TTP) or to a data repository, respectively. 75 patients who met our inclusion criteria (minimum of one year of oral anticoagulation treatment) received a quality-of-life questionnaire via the TTP. Of the 66 returns, 63 responses were then linked to the EMR data in the repository.Conclusion Results from RADAR project proved the technical and organisational feasibility of lawful, pseudonymised data acquisition and the linkage of questionnaires to EMR data. The protecting concepts privacy by design and data minimization (Art. 25 GDPR with Recital 78) were implemented. Without informed consent, secondary use of routine data from ambulatory care which are sufficiently anonymized but still meaningful is all but impossible under current German law.


Subject(s)
Electronic Health Records , Primary Health Care , Germany , Health Services Research , Humans , Privacy
6.
GMS J Med Educ ; 38(5): Doc96, 2021.
Article in English | MEDLINE | ID: mdl-34286076

ABSTRACT

Objective: A competency-based training of medical students that is adapted to the realities of care is required internationally and is being intended in Germany with the Master Plan for Medical Studies 2020. In order to test these competencies, the German National Institute for state examinations in Medicine, Pharmacy and Psychotherapy (IMPP) has developed a concept for the redesign of the final part of the medical licensing examination in Germany. It focuses on general and interprofessional healthcare in the examination with outpatients. The aim of this work is to assess the feasibility of the new final examination on the basis of pilot examinations in family practices and to derive further steps for the national implementation. Methods: Fourteen medical students in their internship year completed a full examination with patients aged 42 to 84 years. Examiners evaluated the examination performance using standardised evaluation forms. Feasibility was qualitatively assessed in terms of compliance with content and time limits, examination results, patient reflections, and implementation in the practice. Results: Students were able to complete all tasks within the given time frame. Based on the evaluation forms, the examiners assessed the performance of the students. Patients appreciated the structured course of the examination in the familiar location of their family practice. For the nationwide implementation of the examination, 2,500 examination practices are required for about 10,000 examinees per year. Four students can then be examined on two days per year in each practice. Conclusions: Oral-practical examinations with outpatients in general medical practices can be carried out successfully throughout the nation. An implementation of the examinations throughout Germany requires that medical studies are restructured and that this new curriculum is implemented as intended by the Master Plan for Medical Studies 2020. Furthermore, training and remuneration of examiners together with a legal framework for the new examination must be established.


Subject(s)
Education, Medical, Undergraduate , General Practice , Students, Medical , Adult , Aged , Aged, 80 and over , Curriculum , Education, Medical, Undergraduate/methods , Family Practice , Feasibility Studies , Germany , Humans , Middle Aged
7.
GMS J Med Educ ; 38(2): Doc38, 2021.
Article in English | MEDLINE | ID: mdl-33763523

ABSTRACT

Aim: The Masterplan Medizinstudium 2020 (Masterplan for Medical Studies 2020) focuses on practice-oriented undergraduate training with increased involvement of rural teaching practices. The demand for teaching practices for the final year will increase at all medical faculties in Germany. The project medPJplus at the University Medical Center Göttingen (UMG) presents an approach for successfully acquiring general medical teaching practices in local rural areas. Project outline: The project medPJplus implemented eight measures in cooperation with medical students, interested general practitioners, and regional players in the surrounding districts to attract new teaching practices: we established public relations, accredited practices, organized the didactic training of participating general practitioners, created a digital platform for students that is linked to the nationwide PJ-Portal, and organized information events, workshops, and feedback reports to regional actors. Results: Within one year, a total of 40 new teaching practices with 57 new teachers in the local rural area joined the project in southern Lower Saxony. A three-stage didactic training concept for general practitioners was established at the UMG. A digital platform enhances the visibility of general practitioners and their activities for students. The teaching practices can now be found on the nationwide PJ-Portal. Fourteen students have currently completed their period of the final year in family medicine there. Conclusions: It is possible to acquire rural general medical teaching practices for the final year. This depends on four core elements: addressing and didactic training of interested general practitioners, networking of medical students with teaching physicians and regional actors, digitally presenting teaching practices, and developing solutions for mobility and living space during the final year.


Subject(s)
Curriculum , Education, Medical , Family Practice , Academic Medical Centers , Curriculum/standards , Curriculum/trends , Family Practice/education , Germany , Humans , Students, Medical , Teaching/standards
8.
J Transl Med ; 18(1): 394, 2020 10 19.
Article in English | MEDLINE | ID: mdl-33076938

ABSTRACT

BACKGROUND: Medical data from family doctors are of great importance to health care researchers but seem to be locked in German practices and, thus, are underused in research. The RADAR project (Routine Anonymized Data for Advanced Health Services Research) aims at designing, implementing and piloting a generic research architecture, technical software solutions as well as procedures and workflows to unlock data from family doctor's practices. A long-term medical data repository for research taking legal requirements into account is established. Thereby, RADAR helps closing the gap between the European countries and to contribute data from primary care in Germany. METHODS: The RADAR project comprises three phases: (1) analysis phase, (2) design phase, and (3) pilot. First, interdisciplinary workshops were held to list prerequisites and requirements. Second, an architecture diagram with building blocks and functions, and an ordered list of process steps (workflow) for data capture and storage were designed. Third, technical components and workflows were piloted. The pilot was extended by a data integration workflow using patient-reported outcomes (paper-based questionnaires). RESULTS: The analysis phase resulted in listing 17 essential prerequisites and guiding requirements for data management compliant with the General Data Protection Regulation (GDPR). Based on this list existing approaches to fulfil the RADAR tasks were evaluated-for example, re-using BDT interface for data exchange and Trusted Third Party-approach for consent management and record linkage. Consented data sets of 100 patients were successfully exported, separated into person-identifying and medical data, pseudonymised and saved. Record linkage and data integration workflows for patient-reported outcomes in the RADAR research database were successfully piloted for 63 responders. CONCLUSION: The RADAR project successfully developed a generic architecture together with a technical framework of tools, interfaces, and workflows for a complete infrastructure for practicable and secure processing of patient data from family doctors. All technical components and workflows can be reused for further research projects. Additionally, a Trusted Third Party-approach can be used as core element to implement data privacy protection in such heterogeneous family doctor's settings. Optimisations identified comprise a fully-electronic consent recording using tablet computers, which is part of the project's extension phase.


Subject(s)
Primary Health Care , Software , Europe , Germany , Humans , Workflow
9.
Z Evid Fortbild Qual Gesundhwes ; 149: 22-31, 2019 Dec.
Article in German | MEDLINE | ID: mdl-32165110

ABSTRACT

BACKGROUND AND OBJECTIVES: The use of primary care data gathered from electronic health records in local practices could be an important building block for the future of health services research. However, the risks and reservations associated with using this data for research purposes should not be underestimated. We show the data protection and privacy problems that may arise through secondary analysis of routine primary care data and describe the technical solutions that are available to address these concerns - as a trust-building measure. METHODS: We screened 40 variables that are deemed important for documentation in the electronic health records of primary care physicians and rated the risk of patient re-identification when using these records from routine medical data for research purposes. The criteria used to rate the risk of re-identification were "expert perception" (inferences of a professional observer of phenotypical characteristics which are documented in the 40 variables), "researchable additional knowledge" (knowledge of characteristics of a person through publicly available information and social media networks), and "statistic frequency" according to diagnosis and medication statistics. RESULTS: Diagnoses and reasons for contacting a general practitioner can contain particularly identifiable characteristics such as "obesity" (ICD-10 E66) and "nicotine dependence" (F17). About half of all ICD codes documented in primary care fall below a critical threshold value in their absolute frequency; this is all the more problematic if diagnoses allow for re-identification due to phenotypical characteristics. Medication information holds little potential risk of re-identification of a person. However, the application of medications could be a source of re-identification, e. g., self-injections of insulin or use of inhalators. Information about times and dates are especially sensitive for the re-identification of a person. Sex and age of a patient generally pose no problems, except in the case of very young or very old individuals when these age groups are seldom represented in the practice. DISCUSSION: Routine health data are, in principle, sensitive data. Knowledge about the variables in primary care data gathered from electronic health records in local practices and the evaluation of this data allow us to more accurately estimate the risk of re-identification for the persons concerned. In particular, chronic diagnoses and/or diagnoses in long text, calendar dates for patient contacts and therapies bear a high risk of re-identification. Technical measures such as removing data, masking values and coding should make re-identification considerably more difficult. There will always be a remaining risk of re-identification which should be openly discussed to counteract concerns about a lack of data protection or a sweeping critique of digitization in healthcare.


Subject(s)
Electronic Health Records , General Practitioners , Primary Health Care , Research Design , Delivery of Health Care , Germany , Humans , Risk
10.
Invest Ophthalmol Vis Sci ; 49(8): 3707-14, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18450589

ABSTRACT

PURPOSE: To assess the use of visual evoked potentials (VEPs) for the in vivo detection of impaired visual function in a marmoset model of multiple sclerosis. The sensitivity of the VEP recordings was determined by comparison with magnetic resonance imaging (MRI) and histopathology. METHODS: Baseline VEPs were recorded in six healthy marmoset monkeys in response to light-flash stimulation. Experimental autoimmune encephalomyelitis (EAE) was induced in four of the six monkeys. Clinical scores were assessed daily, and VEPs were recorded every second week. In vivo MRI and subsequent histopathology of the brains and optic nerves were performed at the end of the study. RESULTS: After induction of EAE, all four marmosets exhibited clinical signs between day 26 and 38 after immunization. VEPs were normal during the induction phase of the disease, but deteriorated in amplitude with the occurrence of clinical symptoms in all animals. MRI revealed bilateral optic neuritis and signal alterations in the optic tracts and occipital subcortical white matter in two of the animals. In the remaining two animals, MRI detected signal alterations in the occipital subcortical white matter. Histopathologic results were concordant with the MRI findings. CONCLUSIONS: VEPs are an easily accessible noninvasive tool for measuring visual function and diagnosing impairment of the visual pathway in a marmoset EAE model.


Subject(s)
Autoimmune Diseases/diagnosis , Encephalomyelitis, Autoimmune, Experimental/diagnosis , Evoked Potentials, Visual , Magnetic Resonance Imaging , Optic Nerve/pathology , Optic Neuritis/diagnosis , Visual Pathways/pathology , Animals , Callithrix , Disease Models, Animal , Encephalomyelitis, Autoimmune, Experimental/chemically induced , Female , Male , Multiple Sclerosis/diagnosis , Myelin Proteins , Myelin-Associated Glycoprotein , Myelin-Oligodendrocyte Glycoprotein , Photic Stimulation , Vision Disorders/diagnosis
11.
Neuroimage ; 41(2): 323-34, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18394926

ABSTRACT

Neuritis of the optic nerve is one of the most frequent early symptoms of multiple sclerosis. There are only scarce data correlating magnetic resonance imaging (MRI) contrast alterations with the underlying pathology, that is inflammation, demyelination, and axonal damage. Here we studied optic neuritis in a rat model of experimental autoimmune encephalomyelitis by comparing in vivo MRI findings from multiple techniques (T1, T2, proton density, magnetization transfer) to histopathology. We further assessed a breakdown of the blood-brain barrier by using Gd-DTPA and indirectly estimated the intracellular accumulation of calcium as a consequence of axonal damage by using manganese-enhanced MRI. Hyperintensity on T2-weighted images and signal enhancement after Gd-DTPA were highly sensitive to lesions of the optic nerve but did not differentiate between mild, moderate, and severe damage. Signal reduction on T1-weighted images was less sensitive but correlated well with the severity of tissue damage. No significant changes in magnetization transfer ratio were observed. Manganese ions tended to accumulate in the central parts of the inflamed optic nerve. The resulting signal enhancement at 24 h after administration positively correlated with the severity of axonal loss. Thus, manganese might be an indicator of intracellular calcium accumulation that is known to be associated with axon damage. Although none of the methods alone distinguished between inflammation, demyelination, and reduced axon density, their specific capabilities should prove useful for future in vivo MRI studies of optic neuritis in both animal models and humans.


Subject(s)
Magnetic Resonance Imaging , Optic Neuritis/pathology , Animals , Contrast Media , Disease Models, Animal , Female , Gadolinium DTPA , Image Interpretation, Computer-Assisted , Magnetic Resonance Imaging/methods , Radiographic Image Enhancement/methods , Rats
12.
Neurosci Lett ; 436(1): 72-6, 2008 May 02.
Article in English | MEDLINE | ID: mdl-18359164

ABSTRACT

Axonal degeneration is now recognized as an important pathological feature of multiple sclerosis (MS). Acute axonal damage happens early in the disease course, and therefore early changes might occur in markers in body fluids, such as cerebrospinal fluid (CSF) and blood. In our study we investigated the relevance of serum and CSF markers for axonal damage in patients with clinically isolated syndrome indicative for MS. We measured the concentration of tau, phospho-tau, S100B, Amyloid beta and neuron specific enolase (NSE) in CSF and serum. Interestingly, the NSE concentration in CSF and serum was decreased in clinically isolated syndrome (CIS)-patients in comparison to the control group indicating reduced neuronal metabolic activity in the early stage of the disease. Concerning other biomarkers, we did not observe any changes in the concentrations between groups. Moreover, we did not detect any correlation between Expanded Disability Status Scale (EDSS) and the concentration of investigated proteins.


Subject(s)
Axons/pathology , Biomarkers/analysis , Multiple Sclerosis/metabolism , Multiple Sclerosis/pathology , Nerve Degeneration/metabolism , Adolescent , Adult , Amyloid beta-Peptides/analysis , Amyloid beta-Peptides/metabolism , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoblotting , Male , Nerve Growth Factors/analysis , Nerve Growth Factors/metabolism , Phosphopyruvate Hydratase/analysis , Phosphopyruvate Hydratase/metabolism , S100 Calcium Binding Protein beta Subunit , S100 Proteins/analysis , S100 Proteins/metabolism , tau Proteins/analysis , tau Proteins/metabolism
13.
Exp Neurol ; 201(1): 172-81, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16764858

ABSTRACT

Interferon-beta-1a (IFN-beta-1a) is an approved treatment for multiple sclerosis (MS). It improves the disease course by reducing the relapse rate as well as the persistent neurological deficits. Recent MRI and post-mortem studies revealed that neuronal and axonal damage are most relevant for chronic disability in MS patients. We have characterized previously time course and mechanisms of neuronal apoptosis in a rat model of myelin oligodendrocyte glycoprotein (MOG)-induced optic neuritis. In this animal model, application of IFN-beta-1a three times per week slightly decreases the loss of retinal ganglion cells (RGCs), the neurons that form the axons within the optic nerve. In contrast to neurotrophic factors, this cytokine does not directly protect cultured RGCs from apoptosis. We conclude that IFN-beta-1a is a suitable candidate to be combined with a directly neuroprotective agent in order to further decrease axonal and neuronal degeneration in MS patients.


Subject(s)
Encephalomyelitis, Autoimmune, Experimental/prevention & control , Interferon-beta/pharmacology , Neurons/drug effects , Retinal Ganglion Cells/drug effects , Animals , Antibodies/blood , Apoptosis/drug effects , Cell Survival/drug effects , Cells, Cultured , Encephalomyelitis, Autoimmune, Experimental/immunology , Encephalomyelitis, Autoimmune, Experimental/metabolism , Enzyme-Linked Immunosorbent Assay , Female , Humans , Interferon beta-1a , Mitogen-Activated Protein Kinase 1/metabolism , Myelin Proteins , Myelin-Associated Glycoprotein/immunology , Myelin-Oligodendrocyte Glycoprotein , Nerve Degeneration/metabolism , Nerve Degeneration/pathology , Nerve Degeneration/prevention & control , Neuritis, Autoimmune, Experimental/immunology , Neuritis, Autoimmune, Experimental/metabolism , Neuritis, Autoimmune, Experimental/prevention & control , Neurons/metabolism , Neurons/pathology , Phosphorylation/drug effects , Rats , Rats, Inbred BN , Retinal Ganglion Cells/metabolism , Retinal Ganglion Cells/pathology , Spinal Cord/drug effects , Spinal Cord/metabolism , Up-Regulation/drug effects
14.
Exp Neurol ; 193(1): 163-71, 2005 May.
Article in English | MEDLINE | ID: mdl-15817275

ABSTRACT

In patients with multiple sclerosis (MS), non-remitting deficits are mainly caused by axonal and neuronal damage. We demonstrated previously that myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis in rats provokes severe axonal and neuronal injury even before clinical manifestation of the disease. In our present study, we investigated effects of simvastatin treatment on degeneration of retinal ganglion cell (RGC) bodies as well as their axons during MOG-induced optic neuritis. Electrophysiological functions of optic nerves and RGCs were analyzed in vivo. Although neuroprotective effects of simvastatin have been demonstrated before in other experimental settings, we did not observe an increase in RGC survival nor an improvement of visual functions. As we could not reproduce the anti-inflammatory effects that were observed under statin therapy in other EAE models, we hypothesize that patients suffering from optic neuritis might not take advantage of simvastatin applications.


Subject(s)
Nervous System Autoimmune Disease, Experimental/drug therapy , Neuroprotective Agents/therapeutic use , Optic Neuritis/prevention & control , Retinal Degeneration/prevention & control , Retinal Ganglion Cells/drug effects , Simvastatin/therapeutic use , Animals , Female , Nervous System Autoimmune Disease, Experimental/metabolism , Nervous System Autoimmune Disease, Experimental/pathology , Neuroprotective Agents/pharmacology , Optic Neuritis/metabolism , Optic Neuritis/pathology , Rats , Rats, Inbred BN , Retinal Degeneration/metabolism , Retinal Degeneration/pathology , Retinal Ganglion Cells/metabolism , Retinal Ganglion Cells/pathology , Simvastatin/pharmacology
15.
Brain ; 128(Pt 2): 375-85, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15601662

ABSTRACT

Neurodegenerative processes determine the clinical disease course of multiple sclerosis, an inflammatory autoimmune CNS disease that frequently manifests with acute optic neuritis. None of the established multiple sclerosis therapies has been shown to clearly reduce neurodegeneration. In a rat model of experimental autoimmune encephalomyelitis, we recently demonstrated increased neuronal apoptosis under methylprednisolone therapy, although CNS inflammation was effectively controlled. In the present study, we combined steroid treatment with application of erythropoietin to target inflammatory as well as neurodegenerative aspects. After immunization with myelin oligodendrocyte glycoprotein (MOG), animals were randomly assigned to six treatment groups receiving different combinations of erythropoietin and methylprednisolone, or respective monotherapies. After MOG-induced experimental autoimmune encephalomyelitis became clinically manifest, optic neuritis was monitored by recording visual evoked potentials. The function of retinal ganglion cells, the neurons that form the axons of the optic nerve, was measured by electroretinograms. Functional and histo pathological data of retinal ganglion cells and optic nerves revealed that neuron and axon protection was most effective when erythropoietin treatment that was started at immunization was combined with high-dose methylprednisolone therapy given from days 1 to 3 of MOG-induced experimental autoimmune encephalomyelitis. In contrast, isolated neuronal or axonal protection without clinical benefit was achieved under monotherapy with erythropoietin or methylprednisolone, respectively.


Subject(s)
Encephalomyelitis, Autoimmune, Experimental/drug therapy , Erythropoietin/therapeutic use , Methylprednisolone/therapeutic use , Multiple Sclerosis/drug therapy , Animals , Drug Therapy, Combination , Electroretinography , Encephalomyelitis, Autoimmune, Experimental/pathology , Encephalomyelitis, Autoimmune, Experimental/physiopathology , Evoked Potentials, Visual , Female , Multiple Sclerosis/pathology , Multiple Sclerosis/physiopathology , Neuroprotective Agents/therapeutic use , Optic Nerve/pathology , Optic Nerve/physiopathology , Optic Neuritis/pathology , Optic Neuritis/physiopathology , Optic Neuritis/prevention & control , Rats , Rats, Inbred BN , Recombinant Proteins , Retinal Ganglion Cells/pathology , Retinal Ganglion Cells/physiology , Signal Transduction
16.
Brain Pathol ; 14(4): 378-87, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15605985

ABSTRACT

Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS which leads to demyelination, axonal destruction and neuronal loss in the early stages. Available therapies mainly target the inflammatory component of the disease but fail to prevent neurodegeneration. To investigate the effect of ciliary neurotrophic factor (CNTF) on the survival of retinal ganglion cells (RGCs), the neurons that form the axons of the optic nerve, we used a rat model of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis. Optic neuritis in this model was diagnosed by recording visual evoked potentials, and RGC function was monitored by measuring electroretinograms. This study demonstrates that CNTF has a neuroprotective effect on affected RGCs during acute optic neuritis. Furthermore, we demonstrate that CNTF exerts its neuroprotective effect through activation of the Janus kinase/signal transducer and activator of transcription pathway, mitogen activated protein kinases and a shift in the Bcl-2 family of proteins towards the anti-apoptotic side. In summary, our results demonstrate that CNTF can serve as an effective neuroprotective treatment in a rat model of MS that especially reflects the neurodegenerative aspects of this disease.


Subject(s)
Ciliary Neurotrophic Factor/therapeutic use , Nerve Degeneration/prevention & control , Optic Neuritis/prevention & control , Retinal Ganglion Cells/drug effects , Analysis of Variance , Animals , Blotting, Western/methods , Cell Count/methods , Cell Death/drug effects , DNA-Binding Proteins/metabolism , Drug Combinations , Enzyme Inhibitors/administration & dosage , Evoked Potentials, Visual/drug effects , Evoked Potentials, Visual/physiology , Female , Flavonoids/administration & dosage , Fluorescent Dyes , Gene Expression Regulation/drug effects , Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors , Mitogen-Activated Protein Kinase Kinases/metabolism , Nerve Degeneration/etiology , Optic Nerve/drug effects , Optic Nerve/metabolism , Optic Nerve/pathology , Optic Neuritis/pathology , Photic Stimulation/methods , Proto-Oncogene Proteins c-bcl-2/metabolism , Rats , STAT3 Transcription Factor , Stilbamidines , Time Factors , Trans-Activators/metabolism , Visual Cortex/drug effects , Visual Cortex/physiopathology , bcl-2-Associated X Protein
17.
Neuroreport ; 13(17): 2229-33, 2002 Dec 03.
Article in English | MEDLINE | ID: mdl-12488802

ABSTRACT

Transcranial magnetic stimulation (TMS) is a noninvasive technique for direct stimulation of the neocortex. In the last two decades it is successfully applied in the study of motor and sensory physiology. TMS uses the indirect induction of electrical fields in the brain generated by intense changes of magnetic fields applied to the scalp. It encompasses two widely used waveform configurations: mono-phasic magnetic pulses induce a single current in the brain while biphasic pulses induce at least two currents of inverse direction. As has been shown for the motor cortex, efficacy of repetitive transcranial magnetic stimulation (rTMS) may depend on pulse configuration. In order to clarify this question with regard to visual perception, static contrast sensitivities (sCS) were evaluated before, during, immediately after and 10 minutes after monophasic and biphasic low frequency (1 Hz) rTMS applied to the occipital cortex of 15 healthy subjects. The intensity of stimulation was the phosphene threshold of each individual subject. Using 4 c/d spatial frequency, significant sCS loss was found during and immediately after 10 min of monophasic stimulation, while biphasic stimulation resulted in no significant effect. Ten minutes after the end of stimulation, the sCS values were at baseline level again. However, reversed current flow direction resulted in an increased efficacy of biphasic and decreased efficacy of monophasic stimulation. Our results are in agreement with previous findings showing that primary visual functions, such as contrast detection, can be transiently altered by low frequency transcranial magnetic stimulation. However the effect of modulation significantly depends on the current waveform and direction.


Subject(s)
Transcranial Magnetic Stimulation , Transcutaneous Electric Nerve Stimulation/methods , Visual Cortex/physiology , Visual Perception/physiology , Adult , Contrast Sensitivity/physiology , Female , Functional Laterality/physiology , Genetic Variation/physiology , Humans , Male , Phosphenes/physiology , Reaction Time/physiology , Sensory Thresholds/physiology , Transcranial Magnetic Stimulation/instrumentation , Transcutaneous Electric Nerve Stimulation/instrumentation
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