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1.
Endocr Pract ; 30(3): 187-193, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38122933

RESUMO

OBJECTIVE: To investigate general practitioners' course of action after detection of elevated thyroid stimulating hormone (TSH) levels regarding repeat testing, direct levothyroxine replacement, or neither. METHODS: We conducted a retrospective study of adults without prior evidence of thyroid disease and with a first detection of elevated TSH levels from January 1, 2015, to December 31, 2020, using data from electronic medical records of a Swiss primary care database. We determined the occurrence of either repeat TSH testing or direct levothyroxine initiation in primary care during 12-month follow-up and determined associations with demographic and clinical factors. RESULTS: Of the 1 591 patients included (median age 65 years, 64.4% female, median TSH 5.7 mIU/L), 34.3% received repeat TSH testing and 12.4% received direct levothyroxine replacement in primary care during follow-up. Repeat TSH testing showed the strongest association with overt hypothyroidism and was more common among patients with high primary care utilization and among patients aged 40-64 years compared to patients aged <40 years. Direct levothyroxine initiation was more likely for TSH levels >7 mIU/L, overt hypothyroidism, female patients, and nonurban practices. CONCLUSIONS: While the degree of thyroid dysfunction was the main driver of follow-up, we identified important gaps in the primary care-based monitoring of elevated TSH levels in young patients and in patients with infrequent consultations. We also observed potential overtreatment of women and patients in nonurban areas. Our findings highlight the need for standardization and dissemination of guidelines for the management of elevated TSH levels among general practitioners.


Assuntos
Clínicos Gerais , Hipotireoidismo , Doenças da Glândula Tireoide , Adulto , Humanos , Feminino , Idoso , Masculino , Tiroxina/uso terapêutico , Tireotropina , Estudos Retrospectivos , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/epidemiologia , Hipotireoidismo/diagnóstico , Doenças da Glândula Tireoide/induzido quimicamente
2.
Praxis (Bern 1994) ; 112(12): 589-592, 2023 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-37971481

RESUMO

INTRODUCTION: Misinformation about vaccination leads to vaccination hesitancy. During the SARS-CoV-2 pandemic, different patterns were observed in how misinformation spread on social media, which coined the term "infodemic." There are different approaches to counter misinformation in vaccination, some of which can be implemented in medical practice. This article is an introduction and overview of the phenomenon of misinformation in social media. The article also aims to uncover individual mechanisms that make misinformation appear credible and thus the article aims to function as an "inoculation against the infodemic."


Assuntos
Infodemia , Vacinação , Humanos , Pandemias , SARS-CoV-2 , Comunicação
3.
Swiss Med Wkly ; 153: 40107, 2023 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-37854021

RESUMO

BACKGROUND: Primary care databases collect electronic medical records with routine data from primary care patients. The identification of chronic diseases in primary care databases often integrates information from various electronic medical record components (EMR-Cs) used by primary care providers. This study aimed to estimate the prevalence of selected chronic conditions using a large Swiss primary care database and to examine the importance of different EMR-Cs for case identification. METHODS: Cross-sectional study with 120,608 patients of 128 general practitioners in the Swiss FIRE ("Family Medicine Research using Electronic Medical Records") primary care database in 2019. Sufficient criteria on three individual EMR-Cs, namely medication, clinical or laboratory parameters and reasons for encounters, were combined by logical disjunction into definitions of 49 chronic conditions; then prevalence estimates and measures of importance of the individual EMR-Cs for case identification were calculated. RESULTS: A total of 185,535 cases (i.e. patients with a specific chronic condition) were identified. Prevalence estimates were 27.5% (95% CI: 27.3-27.8%) for hypertension, 13.5% (13.3-13.7%) for dyslipidaemia and 6.6% (6.4-6.7%) for diabetes mellitus. Of all cases, 87.1% (87.0-87.3%) were identified via medication, 22.1% (21.9-22.3%) via clinical or laboratory parameters and 19.3% (19.1-19.5%) via reasons for encounters. The majority (65.4%) of cases were identifiable solely through medication. Of the two other EMR-Cs, clinical or laboratory parameters was most important for identifying cases of chronic kidney disease, anorexia/bulimia nervosa and obesity whereas reasons for encounters was crucial for identifying many low-prevalence diseases as well as cancer, heart disease and osteoarthritis. CONCLUSIONS: The EMR-C medication was most important for chronic disease identification overall, but identification varied strongly by disease. The analysis of the importance of different EMR-Cs for estimating prevalence revealed strengths and weaknesses of the disease definitions used within the FIRE primary care database. Although prioritising specificity over sensitivity in the EMR-C criteria may have led to underestimation of most prevalences, their sex- and age-specific patterns were consistent with published figures for Swiss general practice.


Assuntos
Registros Eletrônicos de Saúde , Atenção Primária à Saúde , Humanos , Estudos Transversais , Suíça/epidemiologia , Doença Crônica
4.
Int J Public Health ; 68: 1605839, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37273771

RESUMO

Objectives: To provide a thorough assessment of the impact of the COVID-19 pandemic on the utilization of inpatient and outpatient mental healthcare in Switzerland. Methods: Retrospective cohort study using nationwide hospital data (n > 8 million) and claims data from a large Swiss health insurer (n > 1 million) in 2018-2020. Incidence proportions of different types of psychiatric inpatient admissions, psychiatric consultations, and psychotropic medication claims were analyzed using interrupted time series models for the general population and for the vulnerable subgroup of young people. Results: Inpatient psychiatric admissions in the general population decreased by 16.2% (95% confidence interval: -19.2% to -13.2%) during the first and by 3.9% (-6.7% to -0.2%) during the second pandemic shutdown, whereas outpatient mental healthcare utilization was not substantially affected. We observed distinct patterns for young people, most strikingly, an increase in mental healthcare utilization among females aged <20 years. Conclusion: Mental healthcare provision for the majority of the population was largely maintained, but special attention should be paid to young people. Our findings highlight the importance of monitoring mental healthcare utilization among different populations.


Assuntos
COVID-19 , Serviços de Saúde Mental , Humanos , Feminino , Adolescente , Estudos Retrospectivos , Suíça/epidemiologia , COVID-19/epidemiologia , Pandemias
5.
Swiss Med Wkly ; 153: 40078, 2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-37243976

RESUMO

BACKGROUND: We aimed to investigate the self-reported health status and behaviours of 7th-grade adolescents, associations with gender and educational track, as well as health issues addressed during routine school doctor consultations in Switzerland. METHODS: Data on health status and behaviours, specifically general well-being, stimulant and addictive substance use, bullying/violence, exercise, nutrition and health protection, and puberty/sexuality, were drawn from routinely collected self-assessment questionnaires from 1076 (of a total of 1126) students from 14 schools in the Swiss canton of Zug in 2020. Data on health issues addressed in school doctor consultations were collected by nine school doctors (for 595 individual consultations). Multilevel logistic regression analyses were used to investigate the association of gender and educational track with unfavourable health status or behaviours. RESULTS: Although 92% (n = 989) of the students reported being happy or satisfied overall, 21% (n = 215) often or almost always felt sad, and 5-10% had repeatedly been seriously physically hurt (n = 67), sexually harassed with words (n = 88) or experienced uncomfortable physical contact (n = 60). Female gender and a lower educational track were associated with unfavourable health status. In 90% (n = 533) of the school doctor consultations, at least one topic of disease prevention or health promotion was addressed, whereby the topics addressed depended strongly on the individual school doctors. CONCLUSIONS: Our findings revealed that unfavourable health status and behaviours were prevalent among adolescents but the health topics addressed in school doctor consultations were not tailored to students' self-reported health issues. A school-based approach that strengthens adolescents' health literacy and provides opportunities for patient-centred counselling has the potential to improve the current and future health of adolescents and, ultimately, adults. To realise this potential, it is essential for school doctors to be sensitised and trained to address students' health concerns. Emphasis should be placed on the importance of patient-centred counselling, the high prevalence of bullying, and gender and educational differences.


Assuntos
Nível de Saúde , Instituições Acadêmicas , Humanos , Adolescente , Feminino , Autorrelato , Suíça , Escolaridade
6.
JAMA Netw Open ; 6(3): e233949, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36943263

RESUMO

Importance: Human papillomavirus vaccination coverage rates lie below desired thresholds in Switzerland. Because general practitioners are the main contact for the relatively rare health issues of many Swiss young adults, primary care offers an important opportunity to provide catch-up human papillomavirus vaccination. Objective: To examine the knowledge, experiences, and attitudes of Swiss university students in the context of receiving human papillomavirus vaccination during primary care visits. Design, Setting, and Participants: This self-administered, cross-sectional, web-based survey study was conducted among students of 3 universities and 1 educational institution for health professions in the Swiss Canton of Zurich. Specific questions about human papillomavirus vaccination experience were directed to respondents who had received at least 1 dose administered by a general practitioner. Responses were collected during 12-week intervals between November 11, 2020, and April 7, 2021, and data were analyzed from August 3 to August 30, 2022. Main Outcomes and Measures: The primary outcome was whether human papillomavirus vaccination had been administered on the patient's or the general practitioner's initiative. Results: The responses of 5524 participants (median [IQR] age, 23 [21-25] years; 3878 women [70.2%]) were analyzed. The survey completion rate was 90.9% (5524 of 6076 students who consented to participate). A total of 2029 respondents (1792 women [46.2%] and 237 men [14.6%]) reported having received at least 1 human papillomavirus vaccination dose, of whom 740 (36.5%) had received at least 1 dose administered by a general practitioner. Among these, 190 respondents (25.7%) reported that vaccine administration had occurred on their request rather than on their general practitioner's initiative. Among all respondents, 4778 (86.5%) wanted to obtain more information about human papillomavirus vaccination at a general practitioner's office, and 2569 (55.3%) rated acute consultations in general practice as inappropriate for addressing human papillomavirus vaccination. Conclusions and Relevance: The findings of this survey study of Swiss university students suggest that primary care shows a high potential for increasing human papillomavirus vaccination coverage rates in Switzerland. However, there was room for improvement in the proactivity of general practitioners, especially with men, and in the attitudes of students toward the appropriateness of acute consultations in general practice for addressing human papillomavirus vaccination.


Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Masculino , Adulto Jovem , Humanos , Feminino , Adulto , Universidades , Papillomavirus Humano , Infecções por Papillomavirus/complicações , Estudos Transversais , Suíça , Conhecimentos, Atitudes e Prática em Saúde , Vacinação , Estudantes , Atenção Primária à Saúde
7.
Lancet Reg Health Eur ; 20: 100438, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36090671

RESUMO

Background: Digital healthcare systems data could provide insights into the global prevalence of chronic kidney disease (CKD). We designed the CaReMe CKD study to estimate the prevalence, key clinical adverse outcomes and costs of CKD across 11 countries. Methods: Individual-level data of a cohort of 2·4 million contemporaneous CKD patients was obtained from digital healthcare systems in participating countries using a pre-specified common protocol; summarized using random effects meta-analysis. CKD and its stages were defined in accordance with current Kidney Disease: Improving Global Outcomes (KDIGO) criteria. CKD was defined by laboratory values or by a diagnosis code. Findings: The pooled prevalence of possible CKD was 10·0% (95% confidence interval 8.5‒11.4; mean pooled age 75, 53% women, 38% diabetes, 60% using renin-angiotensin-aldosterone system inhibitors). Two out of three CKD patients identified by laboratory criteria did not have a corresponding CKD-specific diagnostic code. Among CKD patients identified by laboratory values, the majority (42%) were in KDIGO stage 3A; and this fraction was fairly consistent across countries. The share with CKD based on urine albumin-creatinine ratio (UACR) alone (KDIGO stages one and two) was 29%, with a substantial heterogeneity between countries. Adverse events were common; 6·5% were hospitalized for CKD or heart failure, and 6·2% died, annually. Costs for renal events and heart failure were consistently higher than costs for atherosclerotic events in CKD patients across all countries. Interpretation: We estimate that CKD is present in one out of ten adults. These individuals experience significant adverse outcomes with associated costs. The prevalence of CKD is underestimated when using diagnostic codes alone. There is considerable public health potential in diagnosing CKD and providing treatments to those currently undiagnosed. Funding: The study was sponsored by AstraZeneca.

8.
PLoS One ; 17(8): e0272662, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35951667

RESUMO

BACKGROUND: Chronic kidney disease (CKD) is a common condition in general practice. Data about quality and physician-level variation of CKD care provided by general practitioners is scarce. In this study, we evaluated determinants and variation of achievement of 14 quality indicators for CKD care using electronic medical records data from Swiss general practice during 2013-2019. METHODS: We defined two patient cohorts from 483 general practitioners, one to address renal function assessment in patients with predisposing conditions (n = 47,201, median age 68 years, 48.7% female) and one to address care of patients with laboratory-confirmed CKD (n = 14,654, median age 80 years, 57.5% female). We investigated quality indicator achievement with mixed-effect logistic regression and expressed physician-level variation as intraclass correlation coefficients (ICCs) and range odds ratios (rORs). RESULTS: We observed the highest quality indicator achievement rate for withholding non-steroidal anti-inflammatory drug prescription in patients with CKD staged G2-3b within 12 months of follow-up (82.6%), the lowest for albuminuria assessment within 18 months of follow-up (18.1%). Highest physician-level variation was found for renal function assessment during 18 months of follow-up in patients with predisposing conditions (diabetes: ICC 0.31, rOR 26.5; cardiovascular disease: ICC 0.28, rOR 17.4; hypertension: ICC 0.24, rOR 17.2). CONCLUSION: This study suggests potentially unwarranted variation in general practice concerning RF assessment in patients affected by conditions predisposing for CKD. We further identified potential gaps in quality of CKD monitoring as well as lower quality of CKD care for female patients and patients not affected by comorbidities.


Assuntos
Medicina Geral , Insuficiência Renal Crônica , Idoso , Idoso de 80 Anos ou mais , Albuminúria , Feminino , Humanos , Masculino , Insuficiência Renal Crônica/terapia , Estudos Retrospectivos , Suíça/epidemiologia
9.
Antibiotics (Basel) ; 11(5)2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35625187

RESUMO

Understanding the decision-making strategies of general practitioners (GPs) could help reduce suboptimal antibiotic prescribing. Respiratory tract infections (RTIs) are the most common reason for inappropriate antibiotic prescribing in primary care, a key driver of antibiotic resistance (ABR). We conducted a nationwide prospective web-based survey to explore: (1) The role of C-reactive protein (CRP) point-of-care testing (POCT) on antibiotic prescribing decision-making for RTIs using case vignettes; and (2) the knowledge, attitudes and barriers/facilitators of antibiotic prescribing using deductive analysis. Most GPs (92-98%) selected CRP-POCT alone or combined with other diagnostics. GPs would use lower CRP cut-offs to guide prescribing for (more) severe RTIs than for uncomplicated RTIs. Intermediate CRP ranges were significantly wider for uncomplicated than for (more) severe RTIs (p = 0.001). Amoxicillin/clavulanic acid was the most frequently recommended antibiotic across all RTI case scenarios (65-87%). Faced with intermediate CRP results, GPs preferred 3-5-day follow-up to delayed prescribing or other clinical approaches. Patient pressure, diagnostic uncertainty, fear of complications and lack of ABR understanding were the most GP-reported barriers to appropriate antibiotic prescribing. Stewardship interventions considering CRP-POCT and the barriers and facilitators to appropriate prescribing could guide antibiotic prescribing decisions at the point of care.

10.
Front Pharmacol ; 13: 832994, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35237170

RESUMO

Purpose: The frequency of medication prescribing and polypharmacy has increased in recent years in different settings, including Swiss general practice. We aimed to describe patient age- and sex-specific rates of polypharmacy and of prescriptions of the most frequent medication classes, and to explore practitioner variability in prescribing. Methods: Retrospective cross-sectional study based on anonymized electronic medical records data of 111 811 adult patients presenting to 116 Swiss general practitioners in 2019. We used mixed-effects regression analyses to assess the association of patient age and sex with polypharmacy (≥5 medications) and with the prescription of specific medication classes (second level of the Anatomical Therapeutic Chemical Classification System). Practitioner variability was quantified in terms of the random effects distributions. Results: The prevalence of polypharmacy increased with age from 6.4% among patients aged 18-40 years to 19.7% (41-64 years), 45.3% (65-80 years), and 64.6% (81-92 years), and was higher in women than in men, particularly at younger ages. The most frequently prescribed medication classes were antiinflammatory and antirheumatic products (21.6% of patients), agents acting on the renin-angiotensin system (19.9%), analgesics (18.7%), and drugs for acid related disorders (18.3%). Men were more often prescribed agents targeting the cardiovascular system, whereas most other medications were more often prescribed to women. The highest practitioner variabilities were observed for vitamins, for antiinflammatory and antirheumatic products, and for mineral supplements. Conclusion: Based on practitioner variability, prevalence, and risk potential, antiinflammatory drugs and polypharmacy in older patients appear to be the most pressing issues in current drug prescribing routines.

11.
Nutrients ; 13(8)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34444770

RESUMO

Testing and prescribing vitamin B12 (also known as cobalamin) is increasing in Switzerland but substantial variation among general practitioners (GPs) with respect to testing has been noted. In this study, we aimed at exploring GPs' mindsets regarding vitamin B12 testing and prescribing. A cross-sectional study was conducted using an online survey distributed by e-mail to Swiss GPs. The questionnaire explored mindsets related to testing and prescribing vitamin B12 in specific clinical situations, as well as testing and prescribing strategies. The questionnaire was sent to 876 GPs and 390 GPs responded (44.5%). The most controversial domains for testing and prescribing vitamin B12 were idiopathic fatigue (57.4% and 43.4% of GPs agreed, respectively) and depressive symptoms (53.0% and 35.4% of GPs agreed, respectively). There was substantial variation among GPs with regard to testing strategies (89.5% of GPS used a serum cobalamin test, 71.3% of GPS used holotranscobalamin, and 27.6% of GPs used homocysteine or methylmalonic acid). Intramuscular injection was the predominantly prescribed route of application (median of 87.5% of the prescriptions). In this study, we focus on discordant mindsets that can be specifically targeted by using educational interventions, and research questions that still need answering specifically about the effectiveness of vitamin B12 for idiopathic fatigue.


Assuntos
Medicina Geral , Clínicos Gerais , Médicos/psicologia , Vitamina B 12/administração & dosagem , Adolescente , Adulto , Anemia/diagnóstico , Anemia/tratamento farmacológico , Atitude do Pessoal de Saúde , Técnicas de Laboratório Clínico , Estudos Transversais , Depressão/diagnóstico , Depressão/tratamento farmacológico , Fadiga/diagnóstico , Fadiga/tratamento farmacológico , Feminino , Humanos , Masculino , Polineuropatias , Padrões de Prática Médica , Inquéritos e Questionários , Suíça , Vitamina B 12/sangue , Deficiência de Vitamina B 12/diagnóstico , Deficiência de Vitamina B 12/tratamento farmacológico , Adulto Jovem
12.
Nutrients ; 13(3)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33809274

RESUMO

Vitamin B12 is often used to improve cognitive function, depressive symptoms, and fatigue. In most cases, such complaints are not associated with overt vitamin B12 deficiency or advanced neurological disorders and the effectiveness of vitamin B12 supplementation in such cases is uncertain. The aim of this systematic review and meta-analysis of randomized controlled trials (RCTs) is to assess the effects of vitamin B12 alone (B12 alone), in addition to vitamin B12 and folic acid with or without vitamin B6 (B complex) on cognitive function, depressive symptoms, and idiopathic fatigue in patients without advanced neurological disorders or overt vitamin B12 deficiency. Medline, Embase, PsycInfo, Cochrane Library, and Scopus were searched. A total of 16 RCTs with 6276 participants were included. Regarding cognitive function outcomes, we found no evidence for an effect of B12 alone or B complex supplementation on any subdomain of cognitive function outcomes. Further, meta-regression showed no significant associations of treatment effects with any of the potential predictors. We also found no overall effect of vitamin supplementation on measures of depression. Further, only one study reported effects on idiopathic fatigue, and therefore, no analysis was possible. Vitamin B12 supplementation is likely ineffective for improving cognitive function and depressive symptoms in patients without advanced neurological disorders.


Assuntos
Cognição/efeitos dos fármacos , Depressão/tratamento farmacológico , Suplementos Nutricionais , Fadiga/tratamento farmacológico , Vitamina B 12/uso terapêutico , Vitaminas/uso terapêutico , Humanos
13.
Vaccines (Basel) ; 9(4)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33915931

RESUMO

In Switzerland, the human papillomavirus vaccination (HPVv) coverage rate lies below a desirable threshold. General practitioners (GPs) and pediatricians have been recognized as important providers of the HPVv, but there is little known about their self-attributed role and its relationship with their actual HPVv behavior. Therefore, the objective of this study was to explore the awareness, attitudes, and clinical practices of Swiss GPs and pediatricians concerning HPVv by means of a web-based questionnaire. We analyzed the responses of 422 physicians (72% GPs, 28% pediatricians). A substantial proportion of respondents considered the HPVv "absolutely essential" (54.2% of pediatricians, 30.6% of GPs). GPs indicated spending more time and effort on HPVv counseling for female rather than male patients more often compared to pediatricians (44.0% versus 13.9%, p < 0.001). The weekly number of patients aged 18-26 years seen in practice (p = 0.002) and whether the HPVv was deemed "absolutely essential" (adjusted odds ratio 2.39, 95% confidence interval 1.12-5.08) were factors associated with GPs administering HPVv in their practice. Shortcomings in terms of awareness, effort in the identification of potential vaccination candidates, and the role of male patients were revealed. By addressing these gaps, Swiss primary care providers could contribute to an increase in the national HPVv coverage rate.

14.
J Clin Med ; 9(6)2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32521786

RESUMO

Laboratory tests are frequently ordered by general practitioners (GPs), but little is known about time trends and between-GP variation of their use. In this retrospective longitudinal study, we analyzed over six million consultations by Swiss GPs during the decade 2009-2018. For 15 commonly used test types, we defined specific laboratory testing rates (sLTR) as the percentage of consultations involving corresponding laboratory testing requests. Patient age- and sex-adjusted time trends of sLTR were modeled with mixed-effect logistic regression accounting for clustering of patients within GPs. We quantified between-GP variation by means of intraclass correlation coefficients (ICC). Nine out of the 15 laboratory test types considered showed significant temporal increases, most eminently vitamin D (ten-year odds ratio (OR) 1.88, 95% confidence interval (CI) 1.71-2.06) and glycated hemoglobin (ten-year OR 1.87, 95% CI 1.82-1.92). Test types both subject to substantial increase and high between-GP variation of sLTR were vitamin D (ICC 0.075), glycated hemoglobin (ICC 0.101), C-reactive protein (ICC 0.202), and vitamin B12 (ICC 0.166). Increasing testing frequencies and large between-GP variation of specific test type use pointed at inconsistencies of medical practice and potential overuse.

15.
Exp Neurol ; 311: 205-212, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30312605

RESUMO

Spinocerebellar ataxia type 14 (SCA14) is a dominantly inherited neurodegenerative disease caused by diverse mutations in the Protein Kinase C gamma (PKCγ) gene which is one of the crucial signaling molecules of Purkinje cells. We have previously created a mouse model of SCA14 by transgenic expression of a mutated PKCγ gene causing SCA14 with a mutation in the catalytic domain. Purkinje cells from the mutated mice have a strong reduction of their dendritic tree in organotypic slice cultures typical for increased PKC activity. There was no overt degeneration of Purkinje cells in vivo and the cerebellum appeared morphologically normal with the exception of lobule 7 where abnormal Purkinje cells were present. Besides from mild motor deficits the mice have no major phenotype. We have now done a more extensive study of cerebellar morphology in these mice and show by rapid Golgi staining that there is a marked reduction of Purkinje cell dendritic tree size throughout the cerebellum. Despite this reduction in dendritic tree size, climbing fiber innervation of Purkinje cells as visualized by immunostaining for the vesicular glutamate transporter 2 (vGlut2) appeared normal in most parts of the cerebellum. The same was true for the expression of the activity and plasticity markers pS6, c-Fos and Arc. These finding suggest that the cerebellar cortex in the transgenic mice is functioning fairly normal and that the reduction of dendritic tree size and the increased PKC activity can be compensated in most Purkinje cells. Around cerebellar lobule 7 there was high transgene expression from the L7 promotor and Purkinje cells showed abnormal morphologies. Climbing fiber innervation as well as the expression of the activity and plasticity markers was strongly disturbed in this area. Our results show that there is substantial potential for functional compensation in the cerebellar cortex. In lobule 7, an area with high transgene expression, compensation failed resulting in Purkinje cell degeneration and dysfunction.


Assuntos
Córtex Cerebelar/citologia , Córtex Cerebelar/fisiologia , Modelos Animais de Doenças , Células de Purkinje/fisiologia , Ataxias Espinocerebelares/patologia , Animais , Tamanho Celular , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Ataxias Espinocerebelares/genética , Ataxias Espinocerebelares/fisiopatologia
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