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1.
BMC Health Serv Res ; 24(1): 126, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263025

RESUMO

BACKGROUND: Clinical decision-support (CDS) tools are systems that provide healthcare providers (HCPs) with recommendations based on knowledge and patient-specific factors to facilitate informed decisions. OBJECTIVES: To identify the key components of a CDS tool that are most important to HCPs in caring for older adults with kidney disease, and to understand the facilitators and barriers toward using CDS tools in daily clinical practice. METHODS: Design: A cross-sectional survey of Canadian HCPs was undertaken. DATA COLLECTION: Participants affiliated with a provincial college, nephrology organization, or advocacy body were contacted. The survey was conducted between August and October 2021. INSTRUMENT: A 59-item questionnaire was developed and divided into five main domains/themes. Analysis was done descriptively. RESULTS: Sixty-three participants completed the questionnaire. Physicians (60%) and pharmacists (22%) comprised the majority of the participants. Most of the participants were specialized in nephrology (65%). The most important components in a CDS tool for prescribing to older patients with kidney disease were the safety and efficacy of the medication (89%), the goal of therapy (89%), and patient's quality of life (87%). 90% were willing to use CDS tools and 57% were already using some CDS tools for prescribing. The majority of the participants selected the validation of CDS tools (95%), accompanying the recommendations by the supporting evidence (84%), and the affiliation of the tools with known organizations (84%), as factors that facilitate the use of CDS tools. CONCLUSION: CDS tools are being used and are accepted by HCPs and have value in their assistance in engaging patients in making well-informed decisions.


Assuntos
Nefropatias , Qualidade de Vida , Humanos , Idoso , Estudos Transversais , Canadá , Pessoal de Saúde
2.
Clin Interv Aging ; 14: 753-762, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31118596

RESUMO

Background: Electronic medical record (EMR) alerts may inform point of care decisions, including the decision to prescribe potentially inappropriate medications (PIM) identified in the Beers criteria. EMR alerts may not be considered relevant or informative in the clinician context, leading to a phenomenon colloquially known as "alert fatigue." Objective: To assess the frequency of clinical interaction with EMR alerts and associated deprescribing behaviors in ambulatory settings. Methods: This is a retrospective observational study in two ambulatory clinics (the Kaye Edmonton Clinic Senior's Clinic and the Lynnwood Family Practice Clinic) in Edmonton over an observational period of 30 months. Statistical analysis was done using descriptive statistics, chi-square and regression analysis. Results: The reminder performance for interactions with the alert was 17.2% across the two clinics. The Number Needed to Remind (NNR) or mean number of alerts shown on clinician screens prior to a single interaction of any kind with the alert was 5.8. When actions were defined as a deprescribing (ie discontinuation) event that was related to the alert and that particular interaction in the EMR, the reminder performance was 1.2%, for an NNR of 82.8. Conclusion: The configuration of alerts in the EMR was not associated with a clinically detectable increase in the uptake of the Beers criteria for high hazard medications.


Assuntos
Sistemas de Apoio a Decisões Clínicas/estatística & dados numéricos , Lista de Medicamentos Potencialmente Inapropriados/normas , Idoso , Idoso de 80 Anos ou mais , Sistemas de Apoio a Decisões Clínicas/organização & administração , Desprescrições , Registros Eletrônicos de Saúde/organização & administração , Feminino , Humanos , Masculino , Análise de Regressão , Sistemas de Alerta/normas , Estudos Retrospectivos
3.
J Clin Pharm Ther ; 39(4): 390-8, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24805908

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Since 2007, pharmacists in Alberta have had authority to adapt existing prescriptions and independently prescribe medications after a peer review process. This study aimed to explore and characterize how pharmacists incorporated prescribing into practice 3 years after this legislation was approved. METHODS: We invited pharmacists to participate in semi-structured telephone interviews to discuss their prescribing practices. Pharmacists working in community, primary care network, hospital or other settings were selected using a mix of purposive and random sampling. Two investigators independently analysed each transcript using an Interpretive Description approach and thematically categorized prescribing practices according to the level of adoption. RESULTS AND DISCUSSION: Thirty-eight pharmacists (n = 13 independent prescribers) participated. Eighteen (47%) had a primary practice site from community practice, eight (21%) primary care, five (13%) hospital practice and seven (18%) from other settings including specialty clinics and long-term care. Twenty-eight participants were categorized as adopters and ten as non-adopters in their primary practice setting. Prescribing practices adopted were characterized as product focused, disease focused or patient focused. Sixteen (42%) described product-focused prescribing where they continued an existing therapy or substituted medications based on formulary guidelines. Seven (18%) described disease-focused prescribing where current therapies were adapted or initiated based on a protocol in a specific therapeutic area. Five (13%) described patient-focused prescribing where they initiated therapy based on patient needs and values, their assessment of the patient and best evidence. Non-adopters were not prescribing, but many described provision of disease or patient-focused care where they influenced prescribing by interacting with other members of the healthcare team. Most commonly, community pharmacists participated in product-focused prescribing, whereas hospital and primary care pharmacists practised disease-focused prescribing. WHAT IS NEW AND CONCLUSION: Our data suggest that there have been context-related differences in uptake across practice settings. Despite this, pharmacists in all studied settings engaged in prescribing activities using three approaches and many pharmacists who were not directly prescribing medications reported having involvement in drug therapy decision-making.


Assuntos
Legislação Farmacêutica , Assistência Farmacêutica/organização & administração , Farmacêuticos/organização & administração , Medicamentos sob Prescrição/administração & dosagem , Alberta , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Equipe de Assistência ao Paciente/organização & administração , Assistência Farmacêutica/legislação & jurisprudência , Farmacêuticos/legislação & jurisprudência , Prática Profissional/organização & administração , Papel Profissional
4.
Eur Respir J ; 39(3): 705-11, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21852335

RESUMO

Cigarette smoke is a major cause of chronic obstructive pulmonary disease (COPD) and emphysema. Although cigarette smoke represses cellular proliferation, the molecular mechanisms underlying this phenomenon are unknown. CCAAT/enhancer-binding proteins (C/EBPs) are key regulators of cell cycle progression, differentiation and pro-inflammatory gene expression, are regulated predominantly at the translational level and may be involved in the pathogenesis of COPD. The aim of this study was to assess the effect of cigarette smoke on proliferation and the expression and translational regulation of C/EBPα and C/EBPß in nondiseased primary human lung fibroblasts. Fibroblasts were exposed to cigarette smoke-conditioned medium (10% and 20% for 24 h). Proliferation was determined by [(3)H]thymidine incorporation. Protein expression levels were determined by immunoblotting and translation was monitored using a translation control reporter system. Cigarette smoke significantly reduced fibroblast proliferation and significantly upregulated full-length C/EBPα and C/EBPß proteins due to a shift in the translational control of CEBPA and CEBPB mRNAs. This shift involved the re-initiation of mRNA translation via the regulatory upstream open reading frame, which coincided with increased interleukin-8 release and a decrease in functional elastin level. These findings provide a novel mechanism to understanding the tissue remodelling observed in the lungs of COPD patients.


Assuntos
Proliferação de Células , Fibroblastos/fisiologia , Biossíntese de Proteínas , Fumar/metabolismo , Proteína alfa Estimuladora de Ligação a CCAAT/biossíntese , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Proteína beta Intensificadora de Ligação a CCAAT/biossíntese , Proteína beta Intensificadora de Ligação a CCAAT/genética , Células Cultivadas , Elastina , Regulação da Expressão Gênica/genética , Humanos , Interleucina-8/metabolismo , Fases de Leitura Aberta , Regulação para Cima
5.
Commun Agric Appl Biol Sci ; 75(4): 659-63, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21534475

RESUMO

Phytophthora cambivora was isolated from rooted bases and roots of Castanea sativa, Chamaecyparis lawsoniana and Cotoneaster spp. as well as from water ponds Located in HNS. In the laboratory trials the species colonised leaf blades and stem parts of 3 tested plant species. Differentiated reaction of tested plant species on P. cambivora was observed.


Assuntos
Água Doce/microbiologia , Phytophthora/isolamento & purificação , Doenças das Plantas/microbiologia , Árvores/microbiologia , Phytophthora/genética , Raízes de Plantas/microbiologia
6.
Artigo em Inglês | MEDLINE | ID: mdl-19680944

RESUMO

Control (crops grown in natural conditions) and Fusarium head blight (FHB) damaged (crops inoculated with Fusarium culmorum conidia) grain of four wheat cultivars was ground and sieved into three fractions of different particle size. A series of blended samples differing in content of damaged material were prepared within fractions and cultivars, and diffuse reflectance spectra recorded within the 200-2500 nm wavelength range. Partial least-squares (PLS) models for the percentage of damaged material in blended samples were built for each of twelve series within different spectral ranges, and the root-mean-squared error of cross-validation (RMSECV) was used for the assessment of model performance. Errors using the models were lowest for the finest fraction independent of spectral range; however, their values depended on the cultivar. RMSECV for the finest fraction averaged over cultivars ranged from a little below 3.0 (when the ultraviolet light sub-range was used or participated with another one) to 8.1% (when only the near infrared (NIR) sub-range was used). For the medium and coarse fractions, averaged errors showed the same tendency of dependence on the sub-range(s); however, with higher values that increased with an increase in particle size. In conclusion, within the different fractions of particle size and spectral ranges, the most sensitive to the presence of damaged material were models developed for the finest fraction and when the ultraviolet light sub-range was used in modelling.


Assuntos
Fusarium/isolamento & purificação , Triticum/microbiologia , Análise Multivariada , Tamanho da Partícula , Doenças das Plantas , Espectrofotometria/métodos
7.
Clin Exp Rheumatol ; 27(2): 277-83, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19473569

RESUMO

OBJECTIVE: Osteoporosis treatment in patients who have sustained a hip fracture has been reported to be less then 20%. The objective of this study is to determine the current rate of adherence to osteoporosis practice guidelines in elderly patients post-hip fracture who have undergone rehabilitation. METHODS: Osteoporosis treatment in patients who have sustained a hip fracture has been reported to be less then 20%. The objective of this study is to determine the current rate of adherence to osteoporosis practice guideline in elderly patients post-hip fracture who have undergone rehabilitation. RESULTS: Osteoporosis therapy (any type) was prescribed to 90 (63%) patients, with bisphosphonates prescribed in 90% of these cases. Calcium and vitamin D was prescribed to 130 (90.9%) patients. Of all the study patients, 76 (53%) of patients had at least one contraindication to osteoporosis therapy identified. Having a diagnosis of osteoporosis was the only factor associated with receiving osteoporosis therapy (OR 13.3, p<0.001). CONCLUSION: In this selected patient population the rates of osteoporosis treatment are higher than previously reported but remain suboptimal.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Fraturas do Quadril/reabilitação , Auditoria Médica , Osteoporose/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Fidelidade a Diretrizes , Fraturas do Quadril/complicações , Humanos , Masculino , Osteoporose/complicações , Guias de Prática Clínica como Assunto , Centros de Reabilitação , Estudos Retrospectivos
8.
Hum Exp Toxicol ; 27(12): 883-94, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19273543

RESUMO

Cognitive deficits, including memory deficiencies, are currently deemed one of key symptoms of psychopathologic mental disorders or epilepsy. The impairment of neurocognitive processes could be due to the administered therapy, in particular combined therapy or therapy using antiepileptics of older type. Gabapentin (GBP) is one of new antiepileptics with normothymic properties. It is known that epileptic patients run a significant risk of developing depression and mood changes. Smoking may also have a negative effect on memory processes and efficacy of administered drugs. Note that smoking in pregnant women also leads to neurobehavioral changes in their children. The objective of our research was to evaluate the effect of GBP on memory functions and antidepressant effect in rats not exposed and exposed to tobacco smoke in fetal life. We were also intent on finding whether GBP has an anticonvulsant effect in contact and without contact with tobacco smoke, and whether it affects motor coordination in animals if administered in the dose of 25 mg/kg. Spatial memory of the animals was assessed in the Morris test and the antidepressant effect in the Porsolt test. The ED(50) value was determined in the Swinyard maximum electric shock test, and the effect on motor coordination was assessed in the chimney test. GBP administered in the dose of 25 mg/kg intraperitoneal (i.p.) significantly reduced the immobility time on days 1 and 7 of the test in animals exposed to tobacco smoke, and on days 7 and 14 of the test in rats not exposed to tobacco smoke. Upon single and multiple administration of GBP to animals not exposed to tobacco smoke, the spatial memory improved, whereas in animals exposed to tobacco smoke in fetal life tolerance for procognitive effect was observed on day 21 of the test. It has been found that in rats not exposed to tobacco smoke, ED(50) of GBP was 28.73 mg/kg, whereas in animals exposed to tobacco smoke in fetal life, ED(50) was 46.2 mg/kg. Upon 14 and 21 days of drug administration, motor coordination was impaired in both GBP receiving animal groups. In conclusion, GBP beside its anticonvulsant efficacy also improves memory processes and has antidepressant effect. We also proved that GBP may reverse cognitive deficits concerning working memory induced by prenatal exposure to tobacco smoke and may have antidepressant effect in rats exposed to tobacco smoke.


Assuntos
Aminas/farmacologia , Anticonvulsivantes/farmacologia , Antidepressivos/farmacologia , Comportamento Animal/efeitos dos fármacos , Cognição/efeitos dos fármacos , Ácidos Cicloexanocarboxílicos/farmacologia , Nicotiana , Efeitos Tardios da Exposição Pré-Natal , Fumaça/efeitos adversos , Ácido gama-Aminobutírico/farmacologia , Aminas/administração & dosagem , Animais , Anticonvulsivantes/administração & dosagem , Antidepressivos/administração & dosagem , Ácidos Cicloexanocarboxílicos/administração & dosagem , Depressão/prevenção & controle , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Gabapentina , Exposição por Inalação , Injeções Intraperitoneais , Memória/efeitos dos fármacos , Destreza Motora/efeitos dos fármacos , Gravidez , Ratos , Ratos Wistar , Convulsões/prevenção & controle , Fatores de Tempo , Ácido gama-Aminobutírico/administração & dosagem
9.
Plant Dis ; 92(3): 488, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30769700

RESUMO

Numerous Fusarium species have been associated with Fusarium head blight of wheat. In Poland, Fusarium poae was reported as the dominant species isolated from wheat grain during seasons with low amounts of rainfall during anthesis (1). F. langsethiae was described as a new toxigenic Fusarium species (3) and causal agent of Fusarium head blight (2), which has been isolated from infected oats, wheat, and barley in northern and central Europe (Norway, Austria, Germany, Czech Republic, Denmark, and England) (2). On the basis of morphological similarities, F. langsethiae has long been identified as a "powdery" form of F. poae. However, F. langsethiae produces type A trichothecene toxins such as T-2, whereas F. poae produces nivalenol and other 8-keto trichothecenes, scirpentriol, and 15-acetoxyscirpenol. In 2006, we obtained several isolates of F. langsethiae from kernels collected from winter wheat ears with head blight symptoms. Isolates were collected in the central (Sobiejuchy 52°54'N, 17°43'E; Minikowo 53°29'N, 17°56'E) and northern (Radostowo 53°59'N, 18°45'E) regions of Poland. Strains were isolated on potato dextrose agar (PDA) medium (pH 5.5). Further analyses were conducted on single-spore isolates. Initial species identification of all isolates was conducted on the basis of morphological features. The strains were grown in darkness at 25°C on PDA in plastic petri dishes to diagnose colony color, odor, and growth rate. The cultures also were incubated on saltwater nutrient agar (SNA) at 25°C for 7 days in near-UV light (Philips TLD 36W/08) and darkness in a 12/12-h cycle to promote conidia formation. The calculated average mycelial growth rate per day was based on the difference in millimeters between the colony diameters after 4 and 7 days of incubation. Growth rates ranged from 5.4 to 10.3 mm/day for nine strains. Mycelium was whitish or pinkish white, sparse, and 1 to 3 mm high with no odor. All colonies showed a powdery mycelium surface. Microconidia was napiform or globose, nonseptate, sporadically 1-septate, with an average length of 6.4 µm (range 3.9 to 13.7 µm) and width of 5.6 µm (range 2.9 to 8.8 µm). Microconidia were formed in heads, borne on unbranched or branched monophialides that were 8.5 to 16.3 µm long. All strains had slim, bent monophialides, typical for F. langsethiae, and always a few, short, thick, and squat ones resembling F. poae. In young cultures, monophialides may be formed directly on hyphae. Formation of macroconidia, sclerotia, and chlamydospores were not observed after 3 weeks of incubation. Species identification was confirmed by PCR assay with the use of SCAR (sequence characterized amplified region) primers producing a 310-bp DNA fragment (4), which was deposited in GenBank (Accession No. EU088404). To our knowledge, this is the first report of F. langsethiae in Poland. References: (1) C. Sadowski et al. J. Appl. Genet. 43A:69, 2002. (2) M. Torp and A. Adler. Int. J. Food Microbiol. 95:241, 2004. (3) M. Torp and H. I. Nirenberg. Int. J. Food Microbiol. 95:247, 2004. (4) A. Wilson et al. FEMS Microbiol. Lett. 233:69, 2004.

10.
Food Addit Contam ; 23(11): 1201-7, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17071523

RESUMO

Soft wheat grain samples of the same variety were obtained from a plot where the crop grew under natural conditions (control material) and from a plot where the crop was inoculated with Fusarium culmorum. The grain was ground and sieved with the finest fraction (a particle size less than 0.18 mm) of both materials being used for the preparation of samples in which the content of damaged constituent varied from zero to approximately 84%. Diffuse reflectance spectra of the absorbance from the blended samples were recorded in the 200-2500 nm spectral range and multivariate calibration PLS (Partial Least Squares) models were built within three spectral ranges: 200-2500, 200-1400 and 1400-2500 nm. Before modelling, several variants for spectra pre-processing were tried: multiple scatter correction, single and double differentiation, in all cases with and without centring. Single differentiation followed by centring was found to be the best method for spectra pre-processing in all spectral ranges. Very good calibration models were obtained for the whole and shorter wavelengths spectral ranges, allowing the detection of 1.50 and 0.76% of the content of scab-damaged constituent, respectively. Two-dimensional correlation spectroscopy applied to the set of spectra enabled the assignment of spectral bands and an analysis of changes in the chemical composition caused by scab damage. It was found that the content of protein and lipids increased with an increase of the scab-damaged constituent, whereas the content of moisture and starch decreased.


Assuntos
Fusarium , Doenças das Plantas/microbiologia , Espectrofotometria/métodos , Triticum/química , Análise dos Mínimos Quadrados , Extratos Vegetais/análise
11.
Rev Med Suisse ; 2(57): 702-4, 707-8, 2006 Mar 15.
Artigo em Francês | MEDLINE | ID: mdl-16604870

RESUMO

Septic arthritis is a medical emergency that may be associated with significant mortality (10-15%) and morbidity (25-50%), in case of delayed management. When septic arthritis is suspected, arthrocentesis and culture of the synovial fluid are the gold standard. The absence of fever, rigors, leukocytosis or elevated erythrocyte sedimentation rate does not exclude the diagnosis of septic arthritis. Age, chronic arthropathy, or arthroplasty are particularly associated with increased morbidity. Therapy consists in antibiotics, joint immobilisation (maximum 3 days) and medical drainage, in case of persisting joint effusion.


Assuntos
Artrite Infecciosa/diagnóstico , Artrite Infecciosa/terapia , Antibacterianos/uso terapêutico , Artrite Infecciosa/epidemiologia , Artrite Infecciosa/microbiologia , Diagnóstico Diferencial , Drenagem , Humanos , Prognóstico , Fatores de Risco
12.
Curr Opin Pediatr ; 13(6): 591-7, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11753113

RESUMO

Bulimia nervosa is a common eating disorder in adolescent women. Biological, psychological, and social factors are implicated in onset and important in treatment. Diagnosis of the syndrome, but not its subtypes, can be made well using the DSM-IV system. Screening tools, laboratory findings, and physical findings can be helpful in making the diagnosis. Comorbid disorders include affective disorders, addictive disorders, anxiety disorders, personality disorders, and anorexia nervosa. The etiology of bulimia nervosa is complex, with biologic, psychological, social, and family factors, which likely differ somewhat from patient to patient. Treatment, accordingly, should be comprehensive, individualized, and multifaceted. Many patients respond well to the use of an antidepressant, and cognitive-behavioral therapy is a useful approach for many patients. Combining these two treatments seems to be a good strategy. Environmental and family issues also need to be addressed. Many patients are treated insufficiently. More research on bulimia nervosa specific to adolescence is needed.


Assuntos
Bulimia , Adolescente , Antidepressivos/uso terapêutico , Terapia Comportamental , Bulimia/diagnóstico , Bulimia/psicologia , Bulimia/terapia , Saúde da Família , Feminino , Humanos
13.
J Consult Clin Psychol ; 69(4): 683-98, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11550734

RESUMO

Expert ratings and confirmatory factor analyses were used to develop an alternative system for scoring the Child Behavior Checklist (CBCL; T. M. Achenbach, 1991) to measure specific dimensions corresponding to current conceptualizations of child symptomatology. Data were from a nonclinic and 2 independent clinic samples. Subscales measuring Anxiety, Attention Problems/Hyperactivity, Conduct Problems, Depression, Oppositional Defiant, Social Problems/Immaturity, and Somatization were created. Logistic regressions were conducted to evaluate the diagnostic efficiency and discrimination of the new and original approaches to scoring the CBCL. Some of the new subscales demonstrated better sensitivity, positive predictive power, and discriminant validity than the original CBCL subscales; however, subscales from both approaches demonstrated low sensitivity. Results support the use of the new subscales for specific research purposes.


Assuntos
Transtornos Mentais/diagnóstico , Equipe de Assistência ao Paciente , Determinação da Personalidade/estatística & dados numéricos , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Adolescente , Sintomas Afetivos/classificação , Sintomas Afetivos/diagnóstico , Sintomas Afetivos/psicologia , Criança , Transtornos do Comportamento Infantil/classificação , Transtornos do Comportamento Infantil/diagnóstico , Transtornos do Comportamento Infantil/psicologia , Pré-Escolar , Feminino , Humanos , Masculino , Transtornos Mentais/classificação , Transtornos Mentais/psicologia , Psicometria , Reprodutibilidade dos Testes
14.
J Consult Clin Psychol ; 69(4): 703-5, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11550736

RESUMO

This article is a response to T. M. Achenbach and L. Dumenci's (2001) commentary concerning L. J. Lengua, C. A. Sadowski, W. N. Friedrich, and J. Fisher's (2001) article proposing an alternative scoring approach for the Child Behavior Checklist. The authors note that T. M. Achenbach and L. Dumenci do not comment on the stated goals of the alternative scoring approach and focus on a limited set of the results to make their argument. Although the original and proposed scoring approaches operate similarly, important differences suggest that the proposed scoring approach is promising for use in specific instances, including identifying distinct etiologies, developmental course, and co-occurrence of specific syndromes. The importance of combining rational and empirical approaches in articulating conceptual definitions and developing measures of child psychopathology is discussed.


Assuntos
Transtornos Mentais/diagnóstico , Determinação da Personalidade/estatística & dados numéricos , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Comorbidade , Humanos , Transtornos Mentais/classificação , Transtornos Mentais/psicologia , Psicometria , Psicopatologia , Reprodutibilidade dos Testes
15.
J Virol ; 75(20): 9753-61, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11559808

RESUMO

DNA methylation, by regulating the transcription of genes, is a major modifier of the eukaryotic genome. DNA methyltransferases (DNMTs) are responsible for both maintenance and de novo methylation. We have reported that human immunodeficiency virus type 1 (HIV-1) infection increases DNMT1 expression and de novo methylation of genes such as the gamma interferon gene in CD4(+) cells. Here, we examined the mechanism(s) by which HIV-1 infection increases the cellular capacity to methylate genes. While the RNAs and proteins of all three DNMTs (1, 3a, and 3b) were detected in Hut 78 lymphoid cells, only the expression of DNMT1 was significantly increased 3 to 5 days postinfection. This increase was observed with either wild-type HIV-1 or an integrase (IN) mutant, which renders HIV replication defective, due to the inability of the provirus to integrate into the host genome. Unintegrated viral DNA is a common feature of many retroviral infections and is thought to play a role in pathogenesis. These results indicate another mechanism by which unintegrated viral DNA affects the host. In addition to the increase in overall genomic methylation, hypermethylation and reduced expression of the p16(INK4A) gene, one of the most commonly altered genes in human cancer, were seen in cells infected with both wild-type and IN-defective HIV-1. Thus, infection of lymphoid cells with integration-defective HIV-1 can increase the methylation of CpG islands in the promoters of genes such as the p16(INK4A) gene, silencing their expression.


Assuntos
Metilases de Modificação do DNA/metabolismo , Genes p16 , HIV-1/fisiologia , Linfócitos/virologia , Linhagem Celular , Metilação de DNA , Metilases de Modificação do DNA/genética , Regulação Enzimológica da Expressão Gênica , HIV-1/enzimologia , HIV-1/genética , Humanos , Integrases/deficiência , Integrases/genética , Linfócitos/metabolismo , Mutação , Regiões Promotoras Genéticas , RNA Mensageiro/análise , Fatores de Tempo
16.
Endocrinology ; 142(9): 3890-900, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11517167

RESUMO

GH is required for normal postnatal growth and metabolism. GH stimulates postnatal growth through induction of IGF-I gene expression. Although the liver is the major site of GH-regulated IGF-I, recent evidence indicates that GH-regulated IGF-I expression in nonhepatic tissues is sufficient for normal postnatal growth. One potentially important nonhepatic site of GH-stimulated IGF-I expression is skeletal muscle, as injection of GH into animals leads to increased IGF-I mRNA in this tissue. Nevertheless, direct effects of GH in skeletal muscle cells in culture have not been reported. We therefore tested the C2C12 myogenic cell line for its response to GH and demonstrate that C2C12 skeletal muscle cells rapidly respond to physiological levels of GH with increased tyrosine phosphorylation of the GH receptor, Janus kinase 2, signal transducer and activator of transcription-5a and -5b, insulin receptor substrate-1, and activation of MAPKs/ERKs and protein kinase B/Akt. In these cells, GH stimulates the expression of IGF-I and two members of the suppressors of cytokine signaling family, cytokine-inducible SH2-containing protein and suppressor of cytokine signaling-2. Treatment of C2C12 myoblasts with either the MAPK kinase inhibitor PD98059 or the PI3K inhibitor wortmannin results in higher levels of GH-induced IGF-I and suppressor of cytokine signaling-2 mRNA expression, suggesting that activation of MAPK and PI3K pathways has an inhibitory role in IGF-I and suppressor of cytokine signaling-2 gene regulation. Therefore, C2C12 cells provide the first in vitro model system to study various aspects of GH action in skeletal muscle.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Hormônio do Crescimento Humano/farmacologia , Fator de Crescimento Insulin-Like I/genética , Proteínas do Leite , Músculo Esquelético/fisiologia , Proteínas/genética , Proteínas Proto-Oncogênicas , Proteínas Repressoras , Animais , Linhagem Celular , Núcleo Celular/metabolismo , DNA/metabolismo , Proteínas de Ligação a DNA/metabolismo , Relação Dose-Resposta a Droga , Genes Reporter/fisiologia , Humanos , Proteínas Imediatamente Precoces/genética , Janus Quinase 2 , Camundongos , Músculo Esquelético/citologia , Fosforilação , Proteínas Tirosina Quinases/metabolismo , RNA Mensageiro/metabolismo , Proteínas Recombinantes , Fator de Transcrição STAT5 , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Proteínas Supressoras da Sinalização de Citocina , Transativadores/metabolismo
17.
Dig Surg ; 18(3): 188-95, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11464008

RESUMO

BACKGROUND/AIMS: Preservation of the pylorus is an accepted alternative procedure to the classical Whipple operation for pancreatic head resection but data describing its value for total pancreatectomy are sparse. METHODS: A prospective analysis of 22 total pancreatectomies performed in a consecutive series of 436 pancreatic resections from 1.11.93 to 1.5.99. RESULTS: 11 patients underwent total pancreatectomy with preservation of the pylorus. Histopathological examination revealed pancreatic adenocarcinoma in 16 cases and duodenal adenocarcinoma in 1 patient, 5 patients had other types of pancreatic neoplasm. In-hospital mortality was 4.5% (n = 1), cumulative morbidity was 59% and reoperations were performed in 9.1% of cases (n = 2). Median follow-up was 37 months (range 5-66). 62% of patients (n = 13) developed tumor recurrence and 13 patients died during the follow-up period with 10 deaths being cancer related. There was no difference concerning postoperative and follow-up morbidity of survival between patients undergoing pylorus-preserving total pancreatectomy or pancreatectomy with gastrectomy. However, postoperative body weight was increased 3, 6, 9 and 12 months following preservation of the pylorus. CONCLUSION: Total pancreatectomy with preservation of the pylorus is a feasible type of resection for all types of pancreatic or ampullary tumors, which shows a similar morbidity and long-term survival but improved nutritional recovery compared with standard total pancreatectomy.


Assuntos
Ampola Hepatopancreática/cirurgia , Neoplasias do Ducto Colédoco/cirurgia , Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Piloro/cirurgia , Adenocarcinoma/cirurgia , Adenocarcinoma Mucinoso/cirurgia , Idoso , Idoso de 80 Anos ou mais , Peso Corporal , Carcinoma Ductal Pancreático/cirurgia , Neoplasias do Ducto Colédoco/patologia , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Pancreatectomia/efeitos adversos , Pancreatectomia/mortalidade , Neoplasias Pancreáticas/patologia , Estudos Prospectivos , Reoperação , Fatores de Tempo , Resultado do Tratamento
18.
J Biol Chem ; 276(23): 20703-10, 2001 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-11279166

RESUMO

Previously, by a yeast 2-hybrid screen, we identified signal transducer and activator of transcription 5b (Stat5b) as a substrate of the insulin receptor (IR). We demonstrated that refeeding of fasted mice leads to rapid activation of Stat5 proteins in liver, skeletal muscle, and fat, suggesting that Stat5b is a physiological target of insulin. Here, we show that injection of glucose or insulin into fasted mice leads to robust activation of both Stat5a and Stat5b in skeletal muscle. In C2C12 myotubes, we find that insulin stimulates tyrosine phosphorylation of Stat5a and Stat5b by 3-5-fold. This degree of Stat5 activation in vitro is significantly lower than what we observe in vivo and inversely correlates with IRS-1/2 levels. We can recapitulate robust insulin activation of Stat5 in C2C12 cells by stable overexpression of the human IR (hIR). To identify insulin-activated genes that are Stat5 targets, we also overexpressed an IR mutant (LA-hIR) that signals normally for mitogen-activated protein kinase- and phosphatidylinositol 3-kinase-dependent pathways but is deficient in Stat5 signaling in response to insulin. We demonstrate that insulin induces the expression of SOCS-2 mRNA in the wild type hIR but not in the LA-hIR-overexpressing cells. The induction of SOCS-3 by insulin is reduced but not lost in the LA-hIR cells. Therefore, our results suggest that insulin induction of SOCS-2, and in part SOCS-3 mRNA expression, is mediated by Stat5 and can be independent of mitogen-activated protein kinase and phosphatidylinositol 3-kinase-signaling pathways.


Assuntos
Proteínas de Ligação a DNA/fisiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Insulina/farmacologia , Proteínas do Leite , Músculo Esquelético/efeitos dos fármacos , Proteínas/genética , RNA Mensageiro/genética , Proteínas Repressoras , Transativadores/fisiologia , Fatores de Transcrição , Animais , Linhagem Celular , Regulação da Expressão Gênica/fisiologia , Genes Reporter , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/metabolismo , Isoformas de Proteínas/fisiologia , Fator de Transcrição STAT5 , Transdução de Sinais , Proteína 3 Supressora da Sinalização de Citocinas , Proteínas Supressoras da Sinalização de Citocina
19.
J Psychol ; 134(6): 634-44, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11092417

RESUMO

The authors investigated the relationships between need for cognition, knowledge, and verbal ability. Participants completed scales that measured their need for cognition, verbal ability, and knowledge about people and events that occurred during the Vietnam War era. Correlational analyses showed that the participants' need for cognition scores were modestly but positively correlated with verbal ability and knowledge and that verbal ability and knowledge were also positively correlated. The correlation between need for cognition and knowledge was small but significant when verbal ability was controlled. The conclusion drawn from these results is that need for cognition contributes to the acquisition of knowledge beyond the contribution of verbal ability.


Assuntos
Cognição , Inteligência , Conhecimento , Aprendizagem Verbal , Adolescente , Adulto , Feminino , Humanos , Individualidade , Masculino , Pessoa de Meia-Idade
20.
J Gastrointest Surg ; 4(5): 443-52, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11077317

RESUMO

During the past decades, the classic Whipple resection (cWhipple) and the pylorus-preserving Whipple (ppWhipple) operation have been advanced for the resection of cancer of the pancreatic head. However, no definitive answer exists as to whether the more conservative ppWhipple operation indeed equalizes the short- and long-term results of the cWhipple procedure. Therefore we conducted a randomized prospective trial in a nonselected series of consecutive patients. Demographics, diagnostic, intraoperative, and histologic findings (tumor type and tumor stage of these patients) as well as postoperative mortality, morbidity, and follow-up after discharge were analyzed. For statistical evaluation Kruskal-Wallis and chi-square tests were used where appropriate. Survival was analyzed according to Kaplan-Meier curves, and differences were examined using the log-rank test. From June 1996 to April 1999, a total of 114 patients with suspected pancreatic or periampullary tumors were prospectively randomized to undergo either a cWhipple or a ppWhipple (intention to treat) operation. Based on the inclusion and exclusion criteria, 77 of these patients were included in the final analysis. Forty had a cWhipple and 37 had a ppWhipple resection. There were no differences with regard to age, sex distribution, ASA classification, histologic classification, UICC stage, length of stay in the intensive care unit, and length of hospital stay. The ppWhipple group had a significantly shorter operative time, reduced blood loss, and fewer blood transfusions. There was no difference in mortality, but the cWhipple group showed a significantly higher total morbidity. The incidence of delayed gastric emptying was identical in both groups. For long-term follow-up, a total of 61 patients with histologically proven pancreatic or periampullary carcinoma were analyzed. There were no differences in tumor recurrence or in long-term survival at a median follow-up of 1.1 years (range 0.1 to 2.9 years). Our initial results demonstrate that the cWhipple and ppWhipple operation are equally radical. However, ppWhipple may be the procedure of choice for the treatment of pancreatic and periampullary cancer.


Assuntos
Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Estudos Prospectivos , Técnicas de Sutura , Resultado do Tratamento
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