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1.
Int J Med Inform ; 187: 105436, 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38583216

RESUMO

BACKGROUND: Identifying patients at high risk of falling is crucial in implementing effective fall prevention programs. While the integration of information systems is becoming more widespread in the healthcare industry, it poses a significant challenge in analysing vast amounts of data to identify factors that could enhance patient safety. OBJECTIVE: To determine fall-associated factors and develop high-performance prediction tools for at-risk patients in acute and sub-acute care services in Australia. METHODS: A retrospective study of 672,400 patients admitted to acute and sub-acute care services within a large metropolitan tertiary health service in Victoria, Australia, between January 1, 2019, and December 31, 2021. Data were obtained from four sources: the Department of Health Victorian Admitted Episodes Dataset, RiskManTM, electronic health records, and the health workforce dataset. Machine learning techniques, including Random Forest and Deep Neural Network models, were used to analyse the data, predict patient falls, and identify the most important risk factors for falls in this population. Model performance was evaluated using accuracy, F1-score, precision, recall, specificity, Matthew's correlation coefficient, and the area under the receiver operating characteristic curve (AUC). RESULTS: The deep neural network and random forest models were highly accurate in predicting hospital patient falls. The deep neural network model achieved an accuracy of 0.988 and a specificity of 0.999, while the RF achieved an accuracy of 0.989 and a specificity of 1.000. The top 20 variables impacting falls were compared across both models, and 12 common factors were identified. These factors can be broadly classified into three categories: patient-related factors, staffing-related factors, and admission-related factors. Although not all factors are modifiable, they must be considered when planning fall prevention interventions. CONCLUSION: The study demonstrated machine learning's potential to predict falls and identify key risk factors. Further validation across diverse populations and settings is essential for broader applicability.

2.
Neth Heart J ; 24(12): 730-739, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27580741

RESUMO

AIM: The aim of this study was to achieve useful insights into pre-hospital management and procedural performance for ST-elevation myocardial infarction (STEMI) in the Netherlands by extrapolating patient characteristics, and procedural and clinical outcomes of the Dutch patient cohort from the APPOSITION-III trial. METHODS: This is a retrospective analysis from the APPOSITION-III trial with respect to the geographical borders of STEMI management. The APPOSITION-III trial was a European registry for the use of the STENTYS self-expandable stent in STEMI patients undergoing primary percutaneous coronary intervention (PPCI). 965 Patients were enrolled mainly in the Netherlands (n = 420, 43.5 % of the overall study population), Germany (n = 165) and France (n = 131). The data from the Dutch cohort were compared with both the overall study population, and the French and German cohorts, respectively, as well as the European Society of Cardiology (ESC) STEMI guidelines. RESULTS: In this trial there was a wide inter-country variation on symptom-to-balloon time, 165 minutes (120-318) in the Netherlands, 270 minutes (180-650) in Germany and 360 minutes (120-480) in France, respectively. In general, a preload of dual antiplatelet therapy (DAPT) combined with heparin was more often performed in the Dutch and French cohort than in the German cohort. DAPT at discharge was high across the whole APPOSITION-III population. No important differences were seen between the different groups according to the endpoints major adverse cardiac event and stent thrombosis. CONCLUSION: In the Dutch cohort of an European multicentre STEMI study (APPOSITION-III trial), the performance in terms of symptom-to-balloon time, and pre-, peri- and post-procedural medical treatment is in line with the recommendations of ESC STEMI guidelines.

3.
Acta Chir Belg ; 114(6): 370-5, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-26021680

RESUMO

BACKGROUND: dequate staging is essential in patients with peritoneal carcinomatosis (PC) from colorectal cancer (CRC) who are candidates for cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC). Metabolic imaging using (18)F-FDG-PET-CT is commonly used to exclude distant metastasis in these patients. Here, we aimed to assess the performance of (18)F-FDG-PET-CT in locoregional staging of the extent of PC. METHODS: Patients with PC from CRC underwent staging including 18F-FDG-PET-CT. In the absence of systemic -dissemination, CRS and oxaliplatin based HIPEC were performed. The extent of PC was quantified during surgery using the modified 7 region count (7RC). The correlation between imaging based estimation of PC extent and surgical 7RC was analyzed using Pearson correlation using both patient based and region based analyses. RESULTS: Fifty-five patients were included between February 2005 and October 2018. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 57%, 98%, 95%, 78% and 82% respectively for non-mucinous tumors and 32%, 100%, 100%, 55% and 63% respectively. (18)F-FDG-PET-CT detected the presence of colorectal PC in 96% of patients suffering from PC with nonmucinous histology and in 60% of patients suffering from PC with mucinous histology. Correlation between imaging 7RC and surgical 7RC was better for PC with nonmucinous histology (r = 0.623) than for PC with mucinous histology (r = -0.180). CONCLUSIONS: Despite of underestimating the exact extent of disease involvement, (18)F-FDG-PET-CT shows good performance in detecting colorectal PC with nonmucinous histology. For colorectal PC with mucinous histology, (18)F-FDG-PET-CT, however, shows poor performance. Since (18)F-FDG-PET-CT did not detect the presence of colorectal PC in all patients in whom long-term survival could be achieved, (18)F-FDG-PET-CT should be implemented into a broad pre-operative assessment strategy.


Assuntos
Neoplasias Colorretais/patologia , Procedimentos Cirúrgicos do Sistema Digestório , Fluordesoxiglucose F18/farmacologia , Estadiamento de Neoplasias , Neoplasias Peritoneais/diagnóstico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Cuidados Pré-Operatórios/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/cirurgia , Compostos Radiofarmacêuticos/farmacologia , Reprodutibilidade dos Testes , Estudos Retrospectivos
4.
Br J Anaesth ; 108(6): 961-5, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22382396

RESUMO

BACKGROUND: Guidelines to minimize the incidence of postoperative nausea and vomiting (PONV) have been implemented in many hospitals. In previous studies, we have demonstrated that guideline adherence is suboptimal and can be improved using decision support (DS). In this study, we investigate whether DS improves patient outcome through improving physician behaviour. METHODS: Medical information of surgical patients is routinely entered in our anaesthesia information management system (AIMS), which includes automated reminders for PONV management based on the simplified risk score by Apfel and colleagues. This study included consecutive adult patients undergoing general anaesthesia for elective non-cardiac surgery who were treated according to the normal clinical routine. The presence of PONV was recorded in the AIMS both during the recovery period and at 24 h. Two periods were studied: one without the use of DS (control period) and one with the use of DS (support period). DS consisted of reminders on PONV both in the preoperative screening clinic and at the time of anaesthesia. RESULTS: In the control period, 981 patients, of whom 378 (29%) were high-risk patients, received general anaesthesia. Overall, 264 (27%) patients experienced PONV within 24 h. In the support period, 1681 patients, of whom 525 (32%) had a high risk for PONV, received general anaesthesia. In this period, only 378 (23%) patients experienced PONV within 24 h after operation. This difference is statistically significant (P=0.01). CONCLUSION: Automated reminders can improve patient outcome by improving guideline adherence.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Náusea e Vômito Pós-Operatórios/prevenção & controle , Sistemas de Alerta , Adulto , Idoso , Feminino , Cirurgia Geral , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto
5.
Acta Clin Belg ; 66(6): 410-5, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22338301

RESUMO

The antistreptolysin O antibody (ASLO) test is often requested in a clinical setting with limited evidence for its usefulness. For this reason, the diagnostic scenario in which ASLO plays an evidence-based role and the analytical performance of the test are critically appraised, taking into account the clinical need and the direct medical cost. Little or no scientific evidence was found for the use of ASLO in patients with pharyngitis, post-streptococcal glomerulonephritis and in adults with rheumatoid arthritis. The clinical relevance of ASLO is restricted to paediatrics, where it contributes to fulfil the diagnosis of acute rheumatic fever (ARF) as per Jones criteria. The standardization of current automated ASLO-latex assays is limited. Attention should be paid to inaccurate reference values and many circumstances causing false positive and false negative results. Because of a low prevalence of ARF in the Western world, a high negative predictive value is obtained for the ASLO test (> 99%). In clinical practice, the result of the test is not urgent. To reduce overconsumption, the clinical laboratory should drive the request behaviour of physicians by a strategic lay-out of the application form. The health insurance/government also contributed by introducing a diagnostic rule for reimbursement.


Assuntos
Antiestreptolisina/sangue , Reações Falso-Negativas , Reações Falso-Positivas , Humanos , Valor Preditivo dos Testes , Febre Reumática/diagnóstico
6.
J Clin Microbiol ; 48(7): 2536-40, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20147642

RESUMO

The purpose of this study was to evaluate the performance of laboratories for the detection and quantification of human herpesvirus 6 (HHV-6) by an external quality assessment (EQA) evaluation. The HHV-6 EQA panel consisted of eight samples containing various concentrations of HHV-6 type A (strain GS) or type B (strain Z29), two samples containing other herpesviruses (i.e., human cytomegalovirus [HCMV] and Epstein-Barr virus [EBV]), and two HHV-6-negative samples. Panel samples were prepared in human plasma, heat inactivated, and lyophilized. Panel distribution, data management, and analysis were coordinated by Quality Control for Molecular Diagnostics (QCMD), Glasgow, United Kingdom. Fifty-one laboratories participated and submitted 57 data sets. Eleven (19.3%) data sets were generated using conventional in-house assays, 11 (19.3%) data sets using commercial real-time PCR assays, and 35 (61.4%) data sets using in-house real-time PCR assays. The presence of HHV-6 DNA at viral loads exceeding 6,000 copies/ml was detected by all participants, and over 80% of the participants still reported correct qualitative results for the sample containing just over 200 copies/ml. The false-positivity rate was 1.8% for both the negative samples and the samples containing HCMV or EBV DNA. The majority (23/33; 69.7%) of quantitative data sets were generated using in-house real-time PCR assays. The standard deviations of the geometric means of the samples ranged from 0.5 to 0.7 log(10). The results of this first international EQA demonstrate encouraging analytical sensitivity for the detection of HHV-6-DNA in human plasma, although we observed extensive interlaboratory variation of quantitative HHV-6 DNA results. Standardization needs to be improved to allow further elucidation of the clinical significance of HHV-6 loads.


Assuntos
Herpesvirus Humano 6 , Técnicas de Diagnóstico Molecular , Carga Viral/métodos , Virologia/métodos , DNA Viral/análise , DNA Viral/isolamento & purificação , Reações Falso-Positivas , Herpesvirus Humano 6/genética , Herpesvirus Humano 6/isolamento & purificação , Humanos , Laboratórios/normas , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/normas , Reação em Cadeia da Polimerase , Controle de Qualidade , Infecções por Roseolovirus/diagnóstico
7.
Eur J Clin Microbiol Infect Dis ; 28(11): 1305-10, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19705175

RESUMO

Since the discovery of human bocavirus (hBoV), the virus has been detected worldwide in respiratory tract samples from young children by various polymerase chain reaction (PCR) assays and real-time PCRs (Q-PCR). Until now, no data have been reported on the presence of hBoV in Belgium and the detection of hBoV in a multiplex Q-PCR setting has not been described. The aim of this study was to develop a fast and reliable multiplex Q-PCR for the simultaneous detection of hBoV DNA and adenovirus (AdV) DNA. During the winter of 2004-2005, 445 nasopharyngeal aspirates (NPAs) were analysed from 404 Belgian children up to 5 years old with acute respiratory tract infections (ARTIs). (Co)infections with hBoV, AdV, respiratory syncytial virus (RSV), human metapneumovirus (hMPV) and influenza A virus were investigated. A viral agent was detected in 61% (n = 272/445) of the NPAs. Multiplex Q-PCR found a prevalence of 11% (n = 51/445) hBoV and 13% (n = 58/445) AdV. Coinfections were more frequently found with AdV (62%; n = 36/58) than with hBoV (49%; n = 25/51). Follow-up samples were available from 22 patients with ARTIs. In three patients, hBoV DNA persisted for one month. Multiplex Q-PCR may help in closing the diagnostic gap by addressing a broader range of potential respiratory pathogens.


Assuntos
Infecções por Adenoviridae/diagnóstico , Infecções por Adenoviridae/epidemiologia , Adenovírus Humanos/isolamento & purificação , Bocavirus Humano/isolamento & purificação , Infecções por Parvoviridae/diagnóstico , Infecções por Parvoviridae/epidemiologia , Reação em Cadeia da Polimerase/métodos , Adenovírus Humanos/genética , Vírus da Doença Aleutiana do Vison/isolamento & purificação , Bélgica/epidemiologia , Pré-Escolar , Técnicas de Laboratório Clínico/métodos , Comorbidade , DNA Viral/genética , DNA Viral/isolamento & purificação , Bocavirus Humano/genética , Humanos , Lactente , Vírus da Influenza A/isolamento & purificação , Masculino , Metapneumovirus/isolamento & purificação , Nasofaringe/virologia , Prevalência , Vírus Sinciciais Respiratórios/isolamento & purificação , Infecções Respiratórias/virologia , Sensibilidade e Especificidade , Fatores de Tempo
8.
Clin Microbiol Infect ; 15(4): 358-63, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19260875

RESUMO

Herpes simplex virus (HSV) has increasingly been associated with pulmonary disease in critically ill patients. However, the clinical relevance of HSV is still a topic of debate. Monitoring of HSV in a quantitative way could potentially give relevant information on its role in the pathogenesis of lower respiratory tract infection. A fast and reliable quantitative real-time PCR (Q-PCR) for the quantitative detection of HSV-1 and HSV-2 DNA was developed. A prospective observational study was performed in an intensive-care unit (ICU) to monitor the HSV viral load in lower respiratory tract aspirates of long-term mechanically ventilated patients. HSV was common in the lower respiratory tract (LRT) of critically ill patients with mechanical ventilation for at least 48 h (62%, n = 65/105). Detection of HSV was significantly associated with prolonged mechanical ventilation (p <0.01), prolonged ICU stay (p <0.01), and development of ventilator-associated pneumonia (p = 0.02). Corticosteroid administration (p <0.01) in the ICU and anti-HSV IgG seropositivity (p <0.01) were risk factors for the occurrence of HSV in the LRT. The fact that no HSV-seronegative patient became positive suggests that all HSV DNA-positive patients had HSV reactivations. Monitoring the HSV viral load in the LRT of critically ill patients showed a typical homogeneous pattern of HSV kinetics. HSV emerged in tracheal and bronchial aspirates after a median of 7 days of intubation (5-11 days), and this was followed by an exponential increase (c. 1 log copies/mL/day) to reach very high HSV peaks (10(6)-10(10) copies/mL) in 78% of the HSV DNA-positive patients.


Assuntos
Herpes Simples/virologia , Herpesvirus Humano 1/isolamento & purificação , Herpesvirus Humano 2/isolamento & purificação , Pneumonia Associada à Ventilação Mecânica/virologia , Reação em Cadeia da Polimerase/métodos , Respiração Artificial/efeitos adversos , Sistema Respiratório/virologia , Idoso , Idoso de 80 Anos ou mais , Estado Terminal , DNA Viral/isolamento & purificação , Feminino , Herpesvirus Humano 1/genética , Herpesvirus Humano 2/genética , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
9.
Vet Rec ; 162(4): 116-9, 2008 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-18223268

RESUMO

Four horses and one pony, ranging in age from one to 11 years, were diagnosed with two different types of odontoid peg fractures. Their clinical signs included reluctance to move the neck and head, dullness, and abnormalities of gait. Radiography was essential for the diagnosis, and the method of treatment varied depending on the severity of the neurological signs, the intended use of the horse, and financial constraints. Optimal treatment requires a technique that allows decompression, anatomical alignment, and stabilisation of the odontoid fracture. If the clinical (neurological) signs are not too severe and the animal shows signs of feeling peripheral pain, conservative treatment can be applied, as is common practice in human surgery. All except the pony made a full recovery.


Assuntos
Cavalos/lesões , Processo Odontoide/lesões , Fraturas da Coluna Vertebral/veterinária , Animais , Eutanásia Animal , Feminino , Coxeadura Animal/etiologia , Masculino , Processo Odontoide/diagnóstico por imagem , Radiografia , Fraturas da Coluna Vertebral/complicações , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/terapia , Contenções/veterinária , Resultado do Tratamento
10.
Vet Rec ; 160(5): 157-8, 2007 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-17277298

RESUMO

A salivary duct fistula in a horse was repaired surgically without using a stent. Seventeen months after the operation the skin incision had healed without complications and the fistula had not recurred.


Assuntos
Doenças dos Cavalos/cirurgia , Implantação de Prótese/veterinária , Ductos Salivares/patologia , Fístula das Glândulas Salivares/veterinária , Stents/veterinária , Animais , Desenho de Equipamento , Doenças dos Cavalos/diagnóstico por imagem , Doenças dos Cavalos/patologia , Cavalos , Masculino , Radiografia , Fístula das Glândulas Salivares/cirurgia , Cicatrização
11.
Int J Dent Hyg ; 4(3): 133-9, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16958741

RESUMO

Surveys among primary school children of group 8 (mainly 12-year olds) in 1988/1989 and 1995/1996 revealed that the dental status in Woudenberg was worse than in other municipalities in the Eemland region. Therefore, several dental preventive activities were started in Woudenberg for children aged 0-12 years. This included fluoride rinsing and teeth brushing lessons at primary schools. So as to evaluate the effect of these school activities, a new survey was carried out in Woudenberg in 2004. The teeth status (DMF-S value, percentage sound teeth, percentage erosion) was investigated by examination. Information regarding dental hygiene behaviour and participation in teeth brushing lessons was obtained by questionnaire. Teeth status (measured by DMF-S value as well as percentage sound teeth) at rinsing schools in 2004 was significantly better than at the same schools in 1995/1996. Multivariate analyses revealed that fluoride rinsing for at least 3 years (besides educational level of parents) is the most determining factor for teeth status independent of other variables. Pupils who never rinsed with fluoride were almost four times more likely to have caries lesions than pupils who rinsed for at least 3 years. This study strongly indicates that long-term rinsing with fluoride has a positive effect on teeth status.


Assuntos
Cariostáticos/uso terapêutico , Cárie Dentária/prevenção & controle , Fluoretos/uso terapêutico , Antissépticos Bucais/uso terapêutico , Erosão Dentária/prevenção & controle , Adolescente , Criança , Índice CPO , Cárie Dentária/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Países Baixos/epidemiologia , Higiene Bucal , Serviços de Odontologia Escolar , Inquéritos e Questionários , Erosão Dentária/epidemiologia
13.
J Biol Chem ; 276(38): 35693-700, 2001 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-11479295

RESUMO

Rapid activation of the IkappaB kinase (IKK) complex is considered an obligatory step in the activation of nuclear factor-kappaB (NF-kappaB) in response to diverse stimuli. Since oxidants have been implicated in the regulation of NF-kappaB, the focus of the present study was the activation of IKK by tumor necrosis factor alpha (TNFalpha) in the presence or absence of hydrogen peroxide (H(2)O(2)). Exposure of mouse alveolar epithelial cells to H(2)O(2) was not sufficient to activate IKK, degrade IkappaBalpha, or activate NF-kappaB. In contrast, TNFalpha induced IKK activity rapidly and transiently resulting in IkappaBalpha degradation and NF-kappaB activation. Importantly, in the presence of H(2)O(2), the ability of TNFalpha to induce IKK activity was markedly decreased and resulted in prevention of IkappaBalpha degradation and NF-kappaB activation. Neither tyrosine kinases nor phosphatidylinositol 3-kinases, known regulators of NF-kappaB by oxidants, were involved in IKK inhibition by H(2)O(2). Direct addition of H(2)O(2) to the immunoprecipitated IKK complex inhibited enzyme activity. Inhibition of IKK activity by H(2)O(2) was associated with direct oxidation of cysteine residues present in the IKK complex and occurred only in enzymatically active IKK. In contrast to previously published observations, our findings demonstrate that the oxidant H(2)O(2) reduces NF-kappaB activation by inhibiting activated IKK activity.


Assuntos
Peróxido de Hidrogênio/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismo , Animais , Linhagem Celular Transformada , Células Cultivadas , Cisteína/metabolismo , DNA/metabolismo , Indução Enzimática , Quinase I-kappa B , Luciferases/biossíntese , Camundongos , Oxirredução , Fosfatidilinositol 3-Quinases/metabolismo , Ligação Proteica , Proteínas Serina-Treonina Quinases/química , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-akt , Fator de Necrose Tumoral alfa/antagonistas & inibidores
14.
Psychiatry Res ; 103(1): 43-9, 2001 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-11472789

RESUMO

Plasma epinephrine and norepinephrine concentrations were measured in pedophiles and normal men both in placebo conditions and after administration of meta-chlorophenylpiperazine (mCPP), a post-synaptic 5-HT2 receptor agonist. The plasma concentrations of catecholamines, in particular epinephrine, were significantly increased in pedophiles. It is concluded that pedophiles may have an increased activity of the sympathoadrenal system.


Assuntos
Catecolaminas/sangue , Epinefrina/sangue , Pedofilia/sangue , Adulto , Catecolaminas/metabolismo , Epinefrina/metabolismo , Humanos , Masculino , Piperazinas/farmacologia , Receptores de Serotonina/efeitos dos fármacos , Agonistas do Receptor de Serotonina/farmacologia
15.
Ned Tijdschr Tandheelkd ; 108(3): 94-7, 2001 Mar.
Artigo em Holandês | MEDLINE | ID: mdl-11383353

RESUMO

In the year 1941 the National Health Services Act came into force in which the insured patients have claims to dentistry. The influence on dental care is beyond any doubt and is illustrated by some examples. The dental care for the youth is mentioned in particular. Special attention is paid to legal regulations concerning the application of fluorides.


Assuntos
Cárie Dentária/prevenção & controle , Cobertura do Seguro/tendências , Seguro Odontológico/legislação & jurisprudência , Legislação Odontológica , Programas Nacionais de Saúde/legislação & jurisprudência , Saúde Bucal , Adulto , Criança , Assistência Odontológica Integral/tendências , Fluoretos Tópicos/uso terapêutico , Humanos , Cobertura do Seguro/normas , Seguro Odontológico/tendências , Países Baixos
16.
J Immunol ; 166(11): 6869-76, 2001 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-11359847

RESUMO

In Alzheimer's disease, neuritic amyloid-beta plaques along with surrounding activated microglia and astrocytes are thought to play an important role in the inflammatory events leading to neurodegeneration. Studies have indicated that amyloid-beta can be directly neurotoxic by activating these glial cells to produce oxygen radicals and proinflammatory cytokines. This report shows that, using primary human monocyte-derived macrophages as model cells for microglia, amyloid-beta(1-42) stimulate these macrophages to the production of superoxide anions and TNF-alpha. In contrast, astrocytes do not produce both inflammatory mediators when stimulated with amyloid-beta(1-42). In cocultures with astrocytes and amyloid-beta(1-42)-stimulated macrophages, decreased levels of both superoxide anion and TNF-alpha were detected. These decreased levels of potential neurotoxins were due to binding of amyloid-beta(1-42) to astrocytes since FACScan analysis demonstrated binding of FITC-labeled amyloid-beta(1-42) to astrocytoma cells and pretreatment of astrocytes with amyloid-beta(1-16) prevented the decrease of superoxide anion in cocultures of human astrocytes and amyloid-beta(1-42)-stimulated macrophages. To elucidate an intracellular pathway involved in TNF-alpha secretion, the activation state of NF-kappaB was investigated in macrophages and astrocytoma cells after amyloid-beta(1-42) treatment. Interestingly, although activation of NF-kappaB could not be detected in amyloid-beta-stimulated macrophages, it was readily detected in astrocytoma cells. These results not only demonstrate that amyloid-beta stimulation of astrocytes and macrophages result in different intracellular pathway activation but also indicate that astrocytes attenuate the immune response of macrophages to amyloid-beta(1-42) by interfering with amyloid-beta(1-42) binding to macrophages.


Assuntos
Peptídeos beta-Amiloides/imunologia , Astrócitos/imunologia , Ativação de Macrófagos/imunologia , Adulto , Peptídeos beta-Amiloides/farmacologia , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Astrocitoma/imunologia , Astrocitoma/metabolismo , Comunicação Celular/efeitos dos fármacos , Comunicação Celular/imunologia , Células Cultivadas , Técnicas de Cocultura , Humanos , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Microglia/efeitos dos fármacos , Microglia/imunologia , Microglia/metabolismo , NF-kappa B/biossíntese , Fragmentos de Peptídeos/farmacologia , Superóxidos/metabolismo , Células Tumorais Cultivadas , Fator de Necrose Tumoral alfa/metabolismo
17.
J Neuroimmunol ; 115(1-2): 144-51, 2001 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-11282164

RESUMO

In this study, the intracellular signal transduction pathways leading to the production of TNF-alpha and superoxide anions by amyloid-beta-stimulated primary human monocyte-derived macrophages was investigated. Using Western blotting and specific inhibitors it is shown that both ERK 1/2 and p38 MAPK signal transduction pathways as well as PKC are involved in the amyloid-beta-stimulated superoxide anion production. In contrast, only ERK 1/2 MAPK seems to be involved in TNF-alpha production: questioning the connection between PKC and ERK 1/2 activation. Our results suggest the use of ERK 1/2 MAPK inhibitors in the prevention of macrophage activation in the context of Alzheimer's disease.


Assuntos
Peptídeos beta-Amiloides/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Fragmentos de Peptídeos/farmacologia , Sistemas do Segundo Mensageiro/fisiologia , Superóxidos/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Células Cultivadas , Inibidores Enzimáticos/farmacologia , Humanos , Macrófagos/citologia , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteína Quinase C/antagonistas & inibidores , Proteína Quinase C/metabolismo , Sistemas do Segundo Mensageiro/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Proteínas Quinases p38 Ativadas por Mitógeno
18.
Neuropsychobiology ; 43(2): 63-9, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11174047

RESUMO

The aims of this study were to examine the late components of the auditory event-related potentials (AERPs), i.e. N(100), P(200) and P(300), in recently detoxified alcohol-dependent patients compared to normal controls and to investigate whether there is a relationship between alterations in these AERPs and signs of activation of the inflammatory response system (IRS). The study subjects consisted of 14 healthy volunteers and 14 recently detoxified alcohol-dependent patients. All subjects performed a two-tone auditory discrimination task, using a standard "oddball" paradigm. The alcohol-dependent patients had their blood sampled to examine IRS markers, such as erythrocyte sedimentation rate (ESR), serum copper concentrations and the number of leukocytes. The P(300) latency was significantly greater in recently detoxified alcohol-dependent patients than in normal controls. There were significant correlations between the P(300) latency and the ESR (r = 0.84, p = 0.009), serum copper concentrations (r = 0.73, p = 0.01) and number of monocytes (r = 0.71, p = 0.006). It is concluded that the P(300) latency is prolonged in detoxified, chronic alcohol-dependent patients and is positively related to indicators of IRS activation. It is hypothesized that activation of the IRS may play a role in the delayed P(300) latency in recently detoxified, alcohol-dependent patients.


Assuntos
Alcoolismo/sangue , Sedimentação Sanguínea , Cobre/sangue , Potenciais Evocados Auditivos , Leucócitos , Fígado/enzimologia , Alcoolismo/enzimologia , Alcoolismo/imunologia , Alcoolismo/terapia , Estudos de Casos e Controles , Potenciais Evocados P300 , Humanos , Contagem de Leucócitos , Monócitos , Neutrófilos
19.
Neuropsychopharmacology ; 24(1): 37-46, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11106874

RESUMO

There is some evidence that hormonal and serotonergic alterations may play a role in the pathophysiology of paraphilias. The aims of the present study were to examine: 1) baseline plasma cortisol, plasma prolactin, and body temperature; and 2) cortisol, prolactin, body temperature, as well as behavioral responses to meta-chlorophenylpiperazine (mCPP) and placebo in pedophiles and normal men. Pedophiles showed significantly lower baseline plasma cortisol and prolactin concentrations and a higher body temperature than normal volunteers. The mCPP-induced cortisol responses were significantly greater in pedophiles than in normal volunteers. In normal volunteers, mCPP-induced a hyperthermic response, whereas in pedophiles no such response was observed. mCPP induced different behavioral responses in pedophiles than in normal men. In pedophiles, but not in normal men, mCPP increased the sensations "feeling dizzy, " "restless," and "strange" and decreased the sensation "feeling hungry". The results suggest that there are several serotonergic disturbances in pedophiles. It is hypothesized that the results are compatible with a decreased activity of the serotonergic presynaptic neuron and a 5-HT2 postsynaptic receptor hyperresponsivity.


Assuntos
Temperatura Corporal/fisiologia , Hidrocortisona/sangue , Pedofilia/sangue , Piperazinas/administração & dosagem , Prolactina/sangue , Agonistas do Receptor de Serotonina/administração & dosagem , Serotonina/metabolismo , Doenças do Córtex Suprarrenal/tratamento farmacológico , Doenças do Córtex Suprarrenal/fisiopatologia , Adulto , Fatores Etários , Temperatura Corporal/efeitos dos fármacos , Humanos , Doenças Hipotalâmicas/tratamento farmacológico , Doenças Hipotalâmicas/fisiopatologia , Masculino , Pedofilia/tratamento farmacológico , Pedofilia/fisiopatologia , Piperazinas/efeitos adversos , Agonistas do Receptor de Serotonina/efeitos adversos
20.
Can J Appl Physiol ; 25(2): 127-38, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10815850

RESUMO

This investigation examines the effects of orally induced alkalosis on serum IGF-I and IGFBP3 concentrations in response to an acute 90-s bout of high intensity cycle exercise. Ten healthy, active men, ages 24.60 +/- 4.90 years, participated in a randomized, double-blind, counterbalanced trial order with a cross-over design. Subjects ingested an experimental bicarbonate solution or a placebo solution. Blood was sampled at baseline; pre-exercise; and 0, 5, 10, and 30 min postexercise. The pH between groups for pre-exercise and postexercise time points differed significantly (p < or = .05) in the experimental condition (from 7.42 +/- 0.01 to 7.35 +/- 0.02) versus the placebo condition (from 7.36 +/- 0.01 to 7.25 +/- 0.03). Increases in IGF-I over resting conditions occurred with placebo conditions at 5 and 10 min postexercise and in the experimental condition at 5 min postexercise. Concentrations of IGFBP3 were elevated above baseline at IP in both experimental and placebo conditions.


Assuntos
Alcalose/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Esforço Físico/fisiologia , Adolescente , Adulto , Alcalose/fisiopatologia , Análise de Variância , Bicarbonatos/administração & dosagem , Estudos Cross-Over , Método Duplo-Cego , Teste de Esforço , Seguimentos , Humanos , Concentração de Íons de Hidrogênio , Masculino , Placebos
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