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1.
J Cancer Educ ; 37(1): 169-178, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-32564251

RESUMO

There are several treatment options for localized prostate cancer with very similar outcome but vary in terms of technique and side effect profiles and risks. Considering the potential difficulty in choosing the best treatment, a patient decision aid (PDA) is used to help patients in their decision-making process. However, the use and applicability of PDA in a country in Asia Pacific region like Malaysia is still unknown. This study aims to evaluate the effectiveness of a PDA modified to the local context in improving patients' knowledge, decisional conflict, and preparation for decision making among men with localized prostate cancer. Sixty patients with localized prostate cancer were randomly assigned to control and intervention groups. A self-administered questionnaire, which evaluate the knowledge on prostate cancer (23 items), decisional conflict (10 items) and preparation for decision-making (10 items), was given to all participants at pre- and post-intervention. Data were analyzed using independent T test and paired T test. The intervention group showed significant improvement in knowledge (p = 0.02) and decisional conflict (p = 0.01) from baseline. However, when compared between the control and intervention groups, there were no significant differences at baseline and post-intervention on knowledge, decisional conflict and preparation for decision-making. A PDA on treatment options of localized prostate cancer modified to the local context in an Asia Pacific country improved patients' knowledge and decisional conflict but did not have significant impact on the preparation for decision-making. The study was also registered under the Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12614000668606 registered on 25/06/2014.


Assuntos
Técnicas de Apoio para a Decisão , Neoplasias da Próstata , Austrália , Tomada de Decisões , Humanos , Masculino , Participação do Paciente , Neoplasias da Próstata/terapia , Centros de Atenção Terciária
2.
HIV Med ; 18(4): 300-304, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27535357

RESUMO

OBJECTIVES: European guidelines recommend HIV testing for individuals presenting with indicator conditions (ICs) including AIDS-defining conditions (ADCs). The extent to which non-HIV specialty guidelines recommend HIV testing in ICs and ADCs is unknown. Our aim was to pilot a methodology in the UK to review specialty guidelines and ascertain if HIV was discussed and testing recommended. METHODS: UK and European HIV testing guidelines were reviewed to produce a list of 25 ADCs and 49 ICs. UK guidelines for these conditions were identified from searches of the websites of specialist societies, the National Institute of Clinical Excellence (NICE) website, the NICE Clinical Knowledge Summaries (CKS) website, the Scottish Intercollegiate Guidance Network (SIGN) website and the British Medical Journal Best Practice database and from Google searches. RESULTS: We identified guidelines for 12 of 25 ADCs (48%) and 36 of 49 (73%) ICs. In total, 78 guidelines were reviewed (range 0-13 per condition). HIV testing was recommended in six of 17 ADC guidelines (35%) and 24 of 61 IC guidelines (39%). At least one guideline recommended HIV testing for six of 25 ADCs (24%) and 16 of 49 ICs (33%). There was no association between recommendation to test and publication year (P = 0.62). CONCLUSIONS: The majority of guidelines for ICs do not recommend testing. Clinicians managing ICs may be unaware of recommendations produced by HIV societies or the prevalence of undiagnosed HIV infection among these patients. We are piloting methods to engage with guideline development groups to ensure that patients diagnosed with ICs/ADCs are tested for HIV. We then plan to apply our methodology in other European settings as part of the Optimising Testing and Linkage to Care for HIV across Europe (OptTEST) project.


Assuntos
Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Programas de Rastreamento/métodos , Guias de Prática Clínica como Assunto , Humanos , Reino Unido
3.
Euro Surveill ; 20(15)2015 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-25953130

RESUMO

HIV seroadaptive behaviours may have contributed to greater sexually transmitted infection (STI) transmission in HIV-positive men who have sex with men(MSM) and to the global increase in STIs. Using multiple national surveillance data sources and population survey data, we estimated the risk of STIs in HIV-positive MSM and assessed whether transmission in HIV-positive MSM has contributed to recent STI epidemics in England. Since 2009, an increasing proportion of STIs has been diagnosed in HIV-positive MSM, and currently, the population rate of acute bacterial STIs is up to four times that of HIV-negative or undiagnosed MSM. Almost one in five of all diagnosed HIV-positive MSM in England had an acute STI diagnosed in 2013. From 2009 to 2013, the odds of being diagnosed with syphilis increased from 2.71 (95% confidence interval (CI) 2.41­3.05, p<0.001) to 4.05 (95%CI 3.70-4.45, p<0.001) in HIV-positive relative to HIV negative/undiagnosed MSM. Similar trends were seen for gonorrhoea and chlamydia. Bacterial STI re-infection rates were considerably higher in HIV-positive MSM over a five-year follow-up period, indicative of rapid transmission in more dense sexual networks.These findings strongly suggest that the sexual health of HIV-positive MSM in England is worsening, which merits augmented public health interventions and continued monitoring.


Assuntos
Epidemias , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Homossexualidade Masculina/estatística & dados numéricos , Infecções Sexualmente Transmissíveis/epidemiologia , Sexo sem Proteção , Adulto , Preservativos/estatística & dados numéricos , Inglaterra/epidemiologia , Gonorreia/epidemiologia , Infecções por HIV/virologia , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Vigilância da População , Prevalência , Estudos Retrospectivos , Assunção de Riscos , Parceiros Sexuais , Sífilis/epidemiologia , Adulto Jovem
4.
Int J Oral Maxillofac Surg ; 53(4): 293-300, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37739816

RESUMO

Midface hypoplasia in syndromic craniosynostosis (SC) may lead to serious respiratory issues. The aim of this study was to analyse the morphometric correlation between midface and cranial base parameters in paediatric SC patients in order to formulate predictive regression models. The computed tomography scans of 18 SC patients and 20 control were imported into Materialise Mimics Medical version 21.0 software for the measurement of multiple craniofacial landmarks and correlation analysis. The results showed a strong correlation of anterior cranial base (SN), posterior cranial base (SBa), and total cranial base (NBa) (r = 0.935) to maxilla length and width (ZMR-ZML) (r = 0.864). The model of NBa = - 1.554 + 1.021(SN) + 0.753(SBa) with R2 = 0.875 is proposed to demonstrate the development of the cranial base that causes a certain degree of midface hypoplasia in SC patients. The formula is supported using a prediction model of ZMR-ZML = 5.762 + 0.920(NBa), with R2 = 0.746. The mean absolute difference and standard deviation between the predicted and true NBa and ZMR-ZML were 2.08 ± 1.50 mm and 3.11 ± 2.32 mm, respectively. The skeletal growth estimation models provide valuable foundation for further analysis and potential clinical application.


Assuntos
Craniossinostoses , Humanos , Criança , Craniossinostoses/diagnóstico por imagem , Face , Base do Crânio , Software , Tomografia Computadorizada por Raios X , Cefalometria
5.
Clin Exp Immunol ; 174(1): 120-8, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23711188

RESUMO

Sitagliptin, a dipeptidyl-peptidase 4 (DPP-4) inhibitor, improves blood glucose control in patients with type 2 diabetes by blocking cleavage of glucagon-like peptide 1 (GLP-1). In type 2 diabetes patients sitagliptin use is associated with an increase in minor infections, and in new-onset type 1 diabetes patients the ability of sitagliptin to dampen autoimmunity is currently being tested. DPP-4, also known as CD26, is expressed on leucocytes and can inactivate many chemokines important for leucocyte migration, as well as act as a co-stimulatory molecule on T cells. Therefore, this study was conducted to test whether sitagliptin is immunomodulatory. In this randomized, placebo-controlled trial, healthy volunteers were given sitagliptin or placebo daily for 28 days, and blood was drawn for immune assays. No significant differences were observed in the percentage of leucocyte subsets within peripheral blood mononuclear cells (PBMCs), plasma chemokine/cytokine levels or cytokines released by stimulation of PBMCs with either lipopolysaccharide (LPS) or anti-CD3. Individuals taking sitagliptin displayed increases in the percentage of cells expressing higher levels of CD26 at early time-points compared to placebo controls, but these differences resolved by day 28 of treatment. Therefore, in healthy volunteers, treatment with sitagliptin daily for 28 days does not overtly alter systemic immune function.


Assuntos
Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Pirazinas/administração & dosagem , Triazóis/administração & dosagem , Dipeptidil Peptidase 4/biossíntese , Dipeptidil Peptidase 4/metabolismo , Inibidores da Dipeptidil Peptidase IV/farmacologia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Método Duplo-Cego , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/imunologia , Peptídeo 1 Semelhante ao Glucagon/antagonistas & inibidores , Peptídeo 1 Semelhante ao Glucagon/sangue , Humanos , Imunomodulação/efeitos dos fármacos , Imunomodulação/imunologia , Avaliação de Resultados em Cuidados de Saúde , Pirazinas/farmacologia , Pirazinas/uso terapêutico , Fosfato de Sitagliptina , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/enzimologia , Subpopulações de Linfócitos T/imunologia , Fatores de Tempo , Fator de Crescimento Transformador beta/biossíntese , Fator de Crescimento Transformador beta/sangue , Triazóis/farmacologia , Triazóis/uso terapêutico , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/imunologia
6.
Ann Oncol ; 21(5): 1064-71, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-19850640

RESUMO

BACKGROUND: Aggressive non-Hodgkin's lymphoma (NHL) represents approximately 60% of lymphomas in the West and even more in the developing world. cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) is recognized as the standard chemotherapy regimen and the addition of rituximab to B-cell subtypes has been shown to significantly improve treatment outcomes. Nevertheless, still a significant fraction of patients is not offered rituximab due to economic reasons. Thus, CHOP is still offered to these patients as well as those with T-cell subtypes. Data from the early 1990s have indicated that the dose intensity (DI) of doxorubicin is a key factor in predicting survival. METHODS: A Medline and Cochrane library search was carried out using the search terms 'CHOP', 'lymphoma' and 'randomized trials'. Eligible trials had CHOP as a control arm and any regimen administering doxorubicin at a higher DI (16.6 mg/m(2)/week) as the investigational arm. Pooling of data was carried out using the mixed effect model. RESULTS: Eight trials were eligible. Patients receiving DI doxorubicin-based regimens had a significantly better overall survival [summary hazard ratio (SHR) 0.82; 95% confidence interval (CI) 0.71-0.96], event-free survival (SHR 0.86; 95% CI 0.75-0.99) and higher complete response rate (summary odds ratio 0.91; 95% CI 0.67-0.97). CONCLUSION: High DI doxorubicin based should be considered in patients with aggressive NHL.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Linfoma não Hodgkin/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/patologia , Prednisona/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida , Resultado do Tratamento , Vincristina/uso terapêutico
7.
Mymensingh Med J ; 28(1): 91-95, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30755556

RESUMO

Diabetes mellitus is one of the leading non-communicable diseases all over the world including Bangladesh. Diabetes is characterized by chronic hyperglycemia and disturbances of carbohydrate, lipid and protein metabolism. Glycated hemoglobin (HbA1c) level of ≥6.5% has been included as a criterion for diagnosis of diabetes. Impaired lipid profile is commonly present in type 2 diabetes. Aim of the study was to investigate the association between serum lipid profile and blood glucose. And hypothesizing that early detection of lipid abnormalities and treatment can minimize the risk for atherogenic cardiovascular disorder and cerebrovascular calamity in patients with type 2 diabetes mellitus (T2DM). This observational cross sectional study was carried out in the department of Biochemistry, Bangladesh Institute of Research & Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM) hospital, Dhaka, Bangladesh from January 2016 to June 2016. A total 105 patients with T2DM of age within the range of 30-45 years were selected for the purpose. Fasting blood glucose (FBG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglyceride (TG) and glycated haemoglobin (HbA1c) levels were evaluated. Test of significance was calculated by unpaired Student's 't' test. Correlation studies (Pearson's correlation) were performed between glycated haemoglobin (HbA1c) and serum lipid profile. Significance was set at p<0.05. Significantly higher mean serum levels of TC, TG and LDL-C and significantly lower mean serum levels of HDL-C were noted in patients with diabetes. Significant correlations were observed between HbA1c value and serum levels of TC, TG and HDL-C (p<0.05) but no significant correlation of HbA1c value with LDL-C in-diabetes patient. The study concluded that HbA1c value correlate well with lipid profile in-diabetes patients. So, HbA1c can be used as a predictor of dyslipidemia in type 2 diabetes.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Dislipidemias/sangue , Hemoglobinas Glicadas/metabolismo , Lipídeos/sangue , Bangladesh , Estudos Transversais , Humanos
8.
Oncogene ; 37(1): 63-74, 2018 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-28869602

RESUMO

DDX3 is a DEAD box RNA helicase with oncogenic properties. RK-33 is developed as a small-molecule inhibitor of DDX3 and showed potent radiosensitizing activity in preclinical tumor models. This study aimed to assess DDX3 as a target in breast cancer and to elucidate how RK-33 exerts its anti-neoplastic effects. High DDX3 expression was present in 35% of breast cancer patient samples and correlated with markers of aggressiveness and shorter survival. With a quantitative proteomics approach, we identified proteins involved in the mitochondrial translation and respiratory electron transport pathways to be significantly downregulated after RK-33 or DDX3 knockdown. DDX3 localized to the mitochondria and DDX3 inhibition with RK-33 reduced mitochondrial translation. As a consequence, oxygen consumption rates and intracellular ATP concentrations decreased and reactive oxygen species (ROS) increased. RK-33 antagonized the increase in oxygen consumption and ATP production observed after exposure to ionizing radiation and reduced DNA repair. Overall, we conclude that DDX3 inhibition with RK-33 causes radiosensitization in breast cancer through inhibition of mitochondrial translation, which results in reduced oxidative phosphorylation capacity and increased ROS levels, culminating in a bioenergetic catastrophe.


Assuntos
Neoplasias da Mama/patologia , RNA Helicases DEAD-box/metabolismo , Mitocôndrias/metabolismo , Biossíntese de Proteínas/efeitos dos fármacos , Radiossensibilizantes/farmacologia , Azepinas/farmacologia , Azepinas/uso terapêutico , Mama/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Linhagem Celular Tumoral , RNA Helicases DEAD-box/antagonistas & inibidores , RNA Helicases DEAD-box/genética , Regulação para Baixo , Feminino , Técnicas de Silenciamento de Genes , Humanos , Imidazóis/farmacologia , Imidazóis/uso terapêutico , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/genética , Mitocôndrias/efeitos da radiação , Oncogenes/efeitos dos fármacos , Proteômica , Radiossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/efeitos da radiação , Análise de Sobrevida
9.
Mol Cell Biol ; 21(19): 6626-39, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11533250

RESUMO

To investigate the transcriptional program underlying thyroid hormone (T3)-induced cell proliferation, cDNA microarrays were used to survey the temporal expression profiles of 4,400 genes. Of 358 responsive genes identified, 88% had not previously been reported to be transcriptionally or functionally modulated by T3. Partitioning the genes into functional classes revealed the activation of multiple pathways, including glucose metabolism, biosynthesis, transcriptional regulation, protein degradation, and detoxification in T3-induced cell proliferation. Clustering the genes by temporal expression patterns provided further insight into the dynamics of T3 response pathways. Of particular significance was the finding that T3 rapidly repressed the expression of key regulators of the Wnt signaling pathway and suppressed the transcriptional downstream elements of the beta-catenin-T-cell factor complex. This was confirmed biochemically, as beta-catenin protein levels also decreased, leading to a decrease in the transcriptional activity of a beta-catenin-responsive promoter. These results indicate that T3-induced cell proliferation is accompanied by a complex coordinated transcriptional reprogramming of many genes in different pathways and that early silencing of the Wnt pathway may be critical to this event.


Assuntos
Inativação Gênica , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Transdução de Sinais , Transativadores , Tri-Iodotironina/farmacologia , Proteínas de Peixe-Zebra , Animais , Divisão Celular , Linhagem Celular , Proteínas do Citoesqueleto/fisiologia , Perfilação da Expressão Gênica , Cinética , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/biossíntese , Ratos , Ativação Transcricional , Proteínas Wnt , beta Catenina
10.
Genet Couns ; 18(4): 383-91, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18286819

RESUMO

Deafness is a heterogeneous disorder showing different patterns of inheritance and involving a multitude of different genes. Mutations in the GJB2 gene encoding connexin 26 (Cx26) protein are a major cause for non-syndromic autosomal recessive and sporadic deafness. Among these mutations, the c.35delG deletion is the most common mutation for sensorineural deafness. One hundred sixteen persons from fifty-eight families were tested by the method based on the principle of PCR-mediated-site-directed mutagenesis (PSDM), followed by a Bsl1 digestion. Mutation c.35delG was diagnosed in sixteen families (11 homozygotes and 5 heterozygotes). The low allelic frequency (17.24%) and low ratio of individuals homozygous (13.8%) and heterozygous (6.9%) for the c.35delG mutation suggest that there are other mutations in the GJB2 gene or other genes responsible for deafness in the Algerian population. This study reports a significant association (P=0.003) between first cousin consanguinity and non-syndromic prelingual deafness.


Assuntos
Alelos , Conexinas/genética , Surdez/etnologia , Surdez/genética , Genes Recessivos/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Adolescente , Adulto , Argélia , Criança , Pré-Escolar , Conexina 26 , Consanguinidade , Feminino , Forminas , Frequência do Gene , Genótipo , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase
11.
Cancer Res ; 60(21): 5922-8, 2000 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-11085504

RESUMO

c-Myc functions through direct activation or repression of transcription. Using cDNA microarray analysis, we have identified c-Myc-responsive genes by comparing gene expression profiles between c-myc null and c-myc wild-type rat fibroblast cells and between c-myc null and c-myc null cells reconstituted with c-myc. From a panel of 4400 cDNA elements, we found 198 genes responsive to c-myc when comparing wild-type or reconstituted cells with the null cells. The plurality of the named c-Myc-responsive genes that were up-regulated, including 30 ribosomal protein genes, are involved in macromolecular synthesis and metabolism, suggesting a major role of c-Myc in the regulation of protein synthetic and metabolic pathways. When ectopically overexpressed, c-Myc induced a different and smaller set of c-Myc-responsive genes as compared with the physiologically expressed c-Myc condition. Thus, these results from expression profiling suggest a new primary function for c-Myc and raise the possibility that the physiological and transforming functions of c-myc may be separable.


Assuntos
Perfilação da Expressão Gênica , Genes myc/fisiologia , Proteínas Proto-Oncogênicas c-myc/fisiologia , Animais , Linhagem Celular , DNA Complementar/genética , Regulação para Baixo , Fibroblastos/fisiologia , Regulação da Expressão Gênica/fisiologia , Análise de Sequência com Séries de Oligonucleotídeos , Biossíntese de Proteínas , Proteínas/metabolismo , Proteínas Proto-Oncogênicas c-myc/biossíntese , Proteínas Proto-Oncogênicas c-myc/genética , Ratos , Regulação para Cima
12.
Mol Endocrinol ; 15(2): 308-18, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11158336

RESUMO

The mechanisms that control life span and age-related phenotypes are not well understood. It has been suggested that aging or at least some of its symptoms are related to a physiological decline in GH levels with age. To test this hypothesis, and to improve our understanding of the cellular and molecular mechanisms behind the aging process, we have analyzed age-induced changes in gene expression patterns through the application of DNA chip technology. In the present study, the aging process was analyzed in rat liver in the presence or absence of GH replacement. Out of 3,000 genes printed on the microarrays, approximately 1,000 were detected in the rat liver. Among these, 47 unique transcripts were affected by the aging process in male rat livers. The largest groups of age-regulated transcripts encoded proteins involved in intermediary metabolism, mitochondrial respiration, and drug metabolism. Approximately 40% of the differentially expressed gene products were normalized after GH treatment. The majority of those transcripts have previously not been shown to be under GH control. The list of gene products that showed normalized expression levels in GH-treated old rats may shed further insight on the action and mechanism behind the positive effects of GH on, for example, fuel metabolism and body composition observed in different animal and human studies.


Assuntos
Envelhecimento/genética , Expressão Gênica/efeitos dos fármacos , Hormônio do Crescimento/farmacologia , Fígado/metabolismo , Animais , DNA Complementar/análise , DNA Complementar/química , Perfilação da Expressão Gênica , Hormônio do Crescimento/administração & dosagem , Terapia de Reposição Hormonal , Fígado/química , Fígado/crescimento & desenvolvimento , Masculino , Mitocôndrias Hepáticas/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Preparações Farmacêuticas/metabolismo , RNA Mensageiro/análise , Ratos , Ratos Sprague-Dawley , Receptores Citoplasmáticos e Nucleares/genética , Fatores de Transcrição/genética
13.
Diabetes Metab ; 41(3): 223-30, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25483023

RESUMO

OBJECTIVE: This study aimed to demonstrate the non-inferiority of 50-week treatment with stepwise insulin intensification of basal-bolus insulin analogues [insulin detemir (IDet) and aspart (IAsp)] versus biphasic insulin aspart 30 (BIAsp30) in insulin-naive type 2 diabetes mellitus (T2DM) patients not controlled by oral glucose-lowering drugs (OGLDs). RESEARCH DESIGN AND METHODS: In this open-label multicentre, multinational, randomized, parallel-arm treat-to-target trial, 403 insulin-naive patients with T2DM in four African countries were randomized to either an IDet+IAsp (n = 200) or BIAsp1-2-3 (n = 203) treatment group. Stepwise insulin intensification was performed at the end of 14, 26 and 38 weeks, depending on HbA1c values. The primary endpoint was change in HbA1c after 50 weeks of treatment. Safety variables were hypoglycaemia incidence, occurrence of adverse events and weight gain. RESULTS: Non-inferiority of the IDet+IAsp versus BIAsp1-2-3 treatment regimen was demonstrated by their similar HbA1c levels at the end of trial (IDet+IAsp: baseline 8.6%, 50 weeks 7.4%; BIAsp1-2-3: baseline 8.7%, 50 weeks 7.3%; full analysis set difference: 0.1% [95% CI: -0.1, 0.3]; per protocol: 0.2% [95% CI: -0.1, 0.4]). At week 50, 40.3 and 44.9% of patients achieved HbA1c <7.0% with IDet+IAsp and BIAsp1-2-3, respectively. The rate of overall hypoglycaemia during the trial was also similar in both groups (IDet+IAsp: 9.4 events/patient-year; BIAsp1-2-3: 9.8 events/patient-year). CONCLUSION: Insulin initiation and intensification using IDet+IAsp was not inferior to BIAsp1-2-3 in insulin-naive patients with T2DM not controlled by OGLDs. Both regimens led to similar reductions in HbA1c values after 50 weeks of treatment.


Assuntos
Insulinas Bifásicas/uso terapêutico , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina Aspart/uso terapêutico , Insulina Detemir/uso terapêutico , Insulina Isófana/uso terapêutico , Adulto , África , Insulinas Bifásicas/administração & dosagem , Insulinas Bifásicas/farmacologia , Feminino , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacologia , Insulina Aspart/administração & dosagem , Insulina Aspart/farmacologia , Insulina Detemir/administração & dosagem , Insulina Detemir/farmacologia , Insulina Isófana/administração & dosagem , Insulina Isófana/farmacologia , Masculino , Pessoa de Meia-Idade
14.
Endocrinology ; 142(7): 3163-76, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11416039

RESUMO

Complementary DNA microarrays containing 3000 different rat genes were used to study the consequences of severe hormonal deficiency (hypophysectomy) on the gene expression patterns in heart, liver, and kidney. Hybridization signals were seen from a majority of the arrayed complementary DNAs; nonetheless, tissue-specific expression patterns could be delineated. Hypophysectomy affected the expression of genes involved in a variety of cellular functions. Between 16-29% of the detected transcripts from each tissue changed expression level as a reaction to this condition. Chronic treatment of hypophysectomized animals with human GH also caused significant changes in gene expression patterns. The study confirms previous knowledge concerning certain gene expression changes in the above-mentioned situations and provides new information regarding hypophysectomy and chronic human GH effects in the rat. Furthermore, we have identified several new genes that respond to GH treatment. Our results represent a first step toward a more global understanding of gene expression changes in states of hormonal deficiency.


Assuntos
Expressão Gênica/efeitos dos fármacos , Expressão Gênica/fisiologia , Hormônio do Crescimento Humano/farmacologia , Hipófise/fisiologia , Animais , Coração/fisiologia , Humanos , Hipofisectomia , Rim/fisiologia , Fígado/fisiologia , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
15.
Am J Med ; 78(4): 617-20, 1985 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-3885731

RESUMO

Sixteen patients with pneumaturia as their only urologic complaint were evaluated during a 38-year period. In three patients, a vesico-enteric fistula was documented. Five patients had an otherwise asymptomatic urinary tract infection. In eight patients, no pathologic process could be identified. These eight patients were women and had a benign course on follow-up. Urine culture gave positive results in all cases with a documented pathologic condition but gave negative results in all cases in which no explanation for pneumaturia could be found. Because of the difficulty in diagnosing a vesico-enteric fistula, all patients with isolated pneumaturia should have a thorough medical and urologic evaluation.


Assuntos
Gases/urina , Adulto , Idoso , Cistoscopia , Infecções por Enterobacteriaceae/urina , Infecções por Escherichia coli/urina , Feminino , Seguimentos , Humanos , Fístula Intestinal/urina , Masculino , Pessoa de Meia-Idade , Infecções por Pseudomonas/urina , Fístula da Bexiga Urinária/urina , Infecções Urinárias/urina , Urografia
16.
Am J Med ; 82(2): 236-8, 1987 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-3812515

RESUMO

Thirty-seven cases of von Hippel-Lindau syndrome are reported. The urinary tract was studied in 23 patients; 15 of them had the renal lesions. Eight of these 15 patients had renal cell carcinoma, which was bilateral in six. Because 80 percent of these patients are seen initially by neurologists or ophthalmologists, the potential for the development of renal cell carcinoma in these patients, the familial nature of the disorder, and the need for early urologic investigations and subsequent close follow-up are emphasized.


Assuntos
Angiomatose/complicações , Carcinoma de Células Renais/complicações , Neoplasias Renais/complicações , Doença de von Hippel-Lindau/complicações , Adolescente , Adulto , Carcinoma de Células Renais/fisiopatologia , Feminino , Seguimentos , Humanos , Neoplasias Renais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Síndrome , Doença de von Hippel-Lindau/fisiopatologia
17.
Neuropharmacology ; 35(3): 257-65, 1996 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8783199

RESUMO

We have investigated the effects of several neurokine/cytokine family members on the level of alpha-bungarotoxin-binding to neuronal nicotinic acetylcholine receptors. Exposure of human neuroblastoma cells (SH-SY5Y and IMR-32) to ciliary neurotrophic factor (CNTF), leukemia inhibitory factor or oncostatin-M resulted in a 30-40% decline in alpha-bungarotoxin receptors on the cells with no decrease seen in either muscarinic acetylcholine receptors or in L-type Ca2+ channels. The level of nicotinic receptor was not affected by the related cytokine, interleukin-6. Treatment of IMR-32 cells with 40 pM CNTF produced a half-maximal decrease of alpha-bungarotoxin binding which compared well with the affinity estimated from binding of 125I-CNTF (Ki approximately 40 pM) and the concentration causing c-fos activation in SH-SY5Y cells, as detected by nuclear run-on assays (60-120 pM). Previous results have indicated that the differentiating agents, phorbol esters and retinoic acid, also decrease nicotinic receptor numbers. Here the effects of CNTF, which did not induce neural differentiation, were enhanced by differentiation with 12-O-tetradecanoylphorbol 13-acetate (10 nM) and prevented by retinoic acid (10 microM). Therefore, the response of neuroblastoma cells to cytokines may be under developmental control. These cells offer a system to examine cytokine responses and signal transduction mechanisms during neural development.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Genes fos , Fatores de Crescimento Neural/farmacologia , Proteínas do Tecido Nervoso/farmacologia , Receptores Nicotínicos/metabolismo , Bungarotoxinas/metabolismo , Fator Neurotrófico Ciliar , Relação Dose-Resposta a Droga , Humanos , Neuroblastoma/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Tretinoína/farmacologia , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/metabolismo
18.
J Med Chem ; 23(9): 1022-6, 1980 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-6106061

RESUMO

Rotenone (1), dihydrorotenone (2), isorotenone (3), mutarotenone (4), and deguelin (12) were found to be potent antagonists of slow-reacting substance of anaphylaxis (SRS-A) in vitro. However, these compounds were also shown to inhibit histamine, serotonin, and acetylcholine at only ten times their IC50 concentrations for SRS-A antagonism. Rotenone (1) and several related compounds were also evaluated in an in vivo guinea pig anaphylaxis model. Several of these compounds and FPL 55712 (I) were effective in prolonging collapse times of animals which received an aerosol challenge of an antigen to which they had been sensitized.


Assuntos
Rotenona/análogos & derivados , Rotenona/farmacologia , SRS-A/antagonistas & inibidores , Acetilcolina/antagonistas & inibidores , Anafilaxia/fisiopatologia , Animais , Cobaias , Antagonistas dos Receptores Histamínicos H1 , Técnicas In Vitro , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Rotenona/síntese química , Antagonistas da Serotonina
19.
Biochem Pharmacol ; 50(10): 1665-71, 1995 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-7503770

RESUMO

Neuronal nicotinic acetylcholine receptors are expressed on a variety of cells in the nervous system where they play key roles in synaptic transmission and information transfer. Little is known, however, about the molecular mechanisms that control their expression, distribution, and function during nervous system development. We have investigated the control of expression during differentiation of one class of acetylcholine receptors that bind alpha-bungarotoxin of human neuroblastoma cells. We report that induction of differentiation of SH-SY5Y, SK-n-SH or IMR-32 cells by the phorbol ester 12-O-tetradecanoyl phorbol 13-myristate (10 nM, TPA) or by retinoic acid resulted in as much as a 70% decline in alpha-bungarotoxin receptors on the cells. The response to the phorbol ester was blocked by the protein kinase C inhibitors staurosporine and bisindolylmaleimide. The decrease in receptors induced by 10 microM retinoic acid was not affected by either agent. However, responses to lower (10 nM) concentrations of retinoic acid were blocked by staurosporine but not bisindolylmaleimide, suggesting a dual mechanism of action for retinoic acid in regulating acetylcholine receptors. It appears that acetylcholine receptors on neuroblastoma cells are regulated during differentiation by both protein kinase C-dependent and -independent mechanisms.


Assuntos
Neurônios/metabolismo , Receptores Nicotínicos/metabolismo , Sítios de Ligação , Bungarotoxinas/metabolismo , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , AMP Cíclico/farmacologia , Regulação para Baixo/efeitos dos fármacos , Ativação Enzimática , Humanos , Radioisótopos do Iodo , Cinética , Neuroblastoma/patologia , Neurônios/citologia , Proteína Quinase C/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Tretinoína/farmacologia , Células Tumorais Cultivadas
20.
Mayo Clin Proc ; 70(1): 28-32, 1995 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-7528865

RESUMO

OBJECTIVE: To report our preliminary experience with visual laser ablation of the prostate (VLAP) for treating bladder outlet obstruction caused by benign prostatic hyperplasia (BPH) and to evaluate its short-term outcome. DESIGN: We reviewed our laser technique in 47 men with symptomatic obstruction caused by BPH who underwent VLAP between July 1992 and April 1993 at our institution, and we compared our results with those reported in the literature. MATERIAL AND METHODS: Our 47 patients were from 43 to 87 years old (mean, 69.6). The mean pretreatment American Urological Association symptom score was 22, mean peak flow rate was 9.5 mL/s, and mean postvoid residual urinary volume was 136 mL. Neodymium:yttrium-aluminum-garnet laser energy was delivered at the 2-, 4-, 8-, and 10-o'clock positions and, when necessary, to the median lobe by one of two lateral-firing laser probes. All but the first four patients were treated on an outpatient basis, and all patients were catheterized (Foley catheter) for 2 to 10 days after VLAP. RESULTS: Of the 47 patients, 32 had data pertaining to a mean follow-up of 5 months; they had a mean symptom score of 10, mean peak flow rate of 15.7 mL/s, and mean postvoid residual volume of 63 mL. In 12 patients, data from a mean follow-up of 11 months were available; they had a mean symptom score of 6, mean peak flow rate of 18.8 mL/s, and mean postvoid residual volume of 10 mL. Perioperative complications (myocardial infarction, thrombophlebitis, and epididymitis) in three patients responded to conservative therapy. Urinary retention occurred for 2 to 60 days after initial removal of the Foley catheter in 12 patients, who then had resumption of spontaneous voiding. In three patients who stated their condition was worse postoperatively, conventional transurethral resection of the prostate was done 6 months after VLAP, and a fourth patient had a persistently obstructive bladder neck incised 8 months after VLAP. CONCLUSION: Our early experience and that reported in the literature indicate that VLAP is a safe and efficacious alternative treatment of obstructive BPH. Although the early results of VLAP rival those of transurethral resection of the prostate, the success rate in treating large prostates should be improved, and long-term results should be assessed to determine the durability of the beneficial effects.


Assuntos
Terapia a Laser/métodos , Hiperplasia Prostática/cirurgia , Obstrução do Colo da Bexiga Urinária/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prostatectomia , Hiperplasia Prostática/complicações , Resultado do Tratamento , Obstrução do Colo da Bexiga Urinária/etiologia
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