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2.
J Clin Pharm Ther ; 39(6): 685-90, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25060527

RESUMO

WHAT IS KNOWN AND OBJECTIVE: The introduction and success of imatinib mesylate (IM) has brought about a paradigm shift in chronic myeloid leukaemia (CML) treatment. However, despite the high efficacy of IM, clinical resistance develops due to a heterogeneous array of mechanisms. Pharmacogenetic variability as a result of genetic polymorphisms could be one of the most important factors influencing resistance to IM. The aim of this study was to investigate the association between genetic variations in drug efflux transporter ABCC1 (MRP1) and ABCC2 (MRP2) genes and response to IM in patients with CML. METHODS: We genotyped 215 Malaysian patients with CML (comprising of two groups with 108 IM resistant and 107 IM responsive) for polymorphisms of ABCC1 (2012G>T and 2168G>A) and ABCC2 (-24C>T, 1249G>A and 3972C>T) genes. Genotype, allele and haplotype frequencies were compared between two groups of patients. Patients with CML were further stratified according to their clinical response to IM into those having cytogenetics and molecular responses, and the associations with genotypes were evaluated. RESULTS AND DISCUSSION: We observed no significant differences in the distribution of any of the tested genotypes between the investigated groups. However, on evaluating the risk association, ABCC2 T₋24 G1249 T3972 haplotype was found to be associated with IM resistance (P = 0·046). These results suggest that haplotype variants -24T and 3972T might be associated with lower expression of ABCC2 protein and reduced transport activity and hence might be contributing to development of IM resistance. WHAT IS NEW AND CONCLUSION: Our results suggest the ABCC2 T₋24 G1249 T3972 haplotype was associated with imatinib resistance. However, the evidence is as yet insufficient to establish this haplotype as a predictive biomarker for response to the drug.


Assuntos
Benzamidas/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Adolescente , Adulto , Idoso , Alelos , Antineoplásicos/uso terapêutico , Povo Asiático/genética , Criança , Estudos Transversais , Resistencia a Medicamentos Antineoplásicos , Feminino , Genótipo , Haplótipos , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Malásia , Masculino , Pessoa de Meia-Idade , Proteína 2 Associada à Farmacorresistência Múltipla , Farmacogenética , Polimorfismo de Nucleotídeo Único , Adulto Jovem
4.
Eur J Cancer Care (Engl) ; 22(6): 824-31, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23834328

RESUMO

The burden of cancer in China is increasing with future psycho-oncological interventions crucial. A systematic review of psycho-oncology research in China was undertaken to assess quantity, design and target trends over time. Medline, PsycINFO, CINAHL, ProQuest, Web of Science (1999-November Week 4, 2012) were searched. Inclusion criteria were: included cancer patients and/or partners or caregivers from resident Chinese populations (either at least 80% of participants are from China, Hong Kong or Taiwan); assessed psychological adjustment relating to cancer and published in English after 1 January 1999 and prior to 30 November 2012. In all, 208 articles met inclusion criteria. Of these: 52 were cross-sectional descriptive quantitative; 30 were cross-sectional descriptive qualitative; 27 were prospective descriptive quantitative; 2 were prospective descriptive qualitative; 18 assessed interventions; 79 presented instrument validation. Publications increased eightfold from 1999 to 2012. Most studies included patients (n = 195) with 11 articles focusing on caregivers and two on patient-caregiver dyads. The most common cancer studied was breast cancer. The psycho-oncology research effort in China is dramatically increasing. A focus on culturally relevant approaches to underpin the evaluation of empirically derived interventions is warranted; as is direction of efforts to other cancers such as lung and prostate.


Assuntos
Pesquisa Biomédica/tendências , Oncologia/tendências , Neoplasias/psicologia , Neoplasias/terapia , Psicologia Médica/tendências , Psicoterapia/tendências , Pesquisa Biomédica/normas , China , Hong Kong , Humanos , Projetos de Pesquisa , Taiwan
5.
J Anim Physiol Anim Nutr (Berl) ; 97(2): 331-41, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22320165

RESUMO

Inflammation and oxidative stress are associated with liver injury and development of liver disease. The transcription factors nuclear factor-kappa beta (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) play critical roles in modulating liver injury and damage. Activation of NF-κB induces production of pro-inflammatory molecules including prostaglandin E2 (PGE2 ), interleukin-8 (IL-8) and macrophage chemotactic protein-1 (MCP-1). Nrf2 regulates genes controlling antioxidants. Our laboratory previously showed that hepatocytes, the primary functional cell type comprising liver tissue, respond to the cytokine interleukin-1 beta (IL-1ß) by increased production of PGE2 , IL-8 and MCP-1. This increase is associated with nuclear translocation of NF-κB. In this study, we evaluated whether primary canine hepatocytes pre-treated with the combination of S-adenosylmethionine (SAMe; 30 and 2000 ng/ml) and silybin (SB; 298 ng/ml), agents with known anti-inflammatory and antioxidant properties, could attenuate IL-1ß-induced inflammation and oxidative stress. The SAMe and SB combination reduced cytokine-induced PGE2 , IL-8 and MCP-1 production while also inhibiting NF-κB nuclear translocation. These changes were accompanied by increased antioxidant enzyme-reduced glutathione (GSH) comparable to control levels. The study shows for the first time that the SAMe and SB combination inhibits both inflammation and oxidative stress through two separate signalling pathways.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Hepatócitos/efeitos dos fármacos , S-Adenosilmetionina/farmacologia , Silimarina/farmacologia , Animais , Biomarcadores , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Dinoprostona/genética , Dinoprostona/metabolismo , Cães , Regulação da Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Hepatócitos/citologia , Interleucina-1beta/farmacologia , Interleucina-8/genética , Interleucina-8/metabolismo , Estresse Oxidativo , Silibina
6.
Osteoporos Int ; 23(2): 573-80, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21380637

RESUMO

SUMMARY: Bisphosphonate treatment rates were examined before and after admission to long-term residential care. Bisphosphonate treatment rates were low (16%) pre-admission but doubled after long-term residential care admission (30%). Men were very undertreated for osteoporosis, while a history of falls with injury was not associated with treatment. INTRODUCTION: To determine the rates and independent correlates of bisphosphonate treatment in elderly residents before and after admission to long-term care (LTC) institutions. METHODS: Information was collected from records of 421 residents of four LTC institutions in Edmonton, Alberta, Canada. Osteoporosis-related diagnoses, treatments, and risk factors including falls in LTC and any adulthood fractures were abstracted. Osteoporosis was defined by physician diagnosis or documented fractures of the hip, spine, or upper extremity. Multivariable analyses were undertaken to determine factors independently associated with bisphosphonate treatment. RESULTS: Mean age was 84 ± 8 years and 290 (70%) were female. Overall, 142 (34%) had previous fractures, 170 (41%) had physician-diagnosed osteoporosis, and 227 (54%) residents met the study's clinical definition of osteoporosis. Of those with osteoporosis, 44 (19%) were men. Before admission, 36 (16%) patients with osteoporosis were treated with bisphosphonates; after admission another 31 (14%) were started on bisphosphonates by LTC physicians. Women were far more likely than men to start bisphosphonate treatment [30 (97%) women vs. 1 (3%) man, adjusted odds ratio (aOR) = 9.20 (95% confidence intervals 1.2,70.5)]. Falls with injury were common [72/227 (31%)] but not associated with bisphosphonate treatment (adjusted p value > 0.5). CONCLUSION: Rates of pre-admission bisphosphonate treatment were low, but did double after LTC admission. Women were almost ten times more likely to start bisphosphonate treatment than men, although one fifth of those with documented osteoporosis were men. Although falls cause most fractures, a history of falls with injury was not associated with bisphosphonate treatment. Our findings suggest that targeting men and residents with falls for treatment with bisphosphonates might be warranted.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Instituição de Longa Permanência para Idosos , Institucionalização , Osteoporose/diagnóstico , Osteoporose/tratamento farmacológico , Acidentes por Quedas , Idoso , Idoso de 80 Anos ou mais , Alberta , Difosfonatos/uso terapêutico , Uso de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Assistência de Longa Duração , Masculino , Osteoporose Pós-Menopausa/diagnóstico , Osteoporose Pós-Menopausa/tratamento farmacológico , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/prevenção & controle , Estudos Retrospectivos , Fatores Sexuais
7.
ESMO Open ; 7(6): 100637, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36423362

RESUMO

BACKGROUND: COGNITION (Comprehensive assessment of clinical features, genomics and further molecular markers to identify patients with early breast cancer for enrolment on marker driven trials) is a diagnostic registry trial that employs genomic and transcriptomic profiling to identify biomarkers in patients with early breast cancer with a high risk for relapse after standard neoadjuvant chemotherapy (NACT) to guide genomics-driven targeted post-neoadjuvant therapy. PATIENTS AND METHODS: At National Center for Tumor Diseases Heidelberg patients were biopsied before starting NACT, and for patients with residual tumors after NACT additional biopsy material was collected. Whole-genome/exome and transcriptome sequencing were applied on tumor and corresponding blood samples. RESULTS: In the pilot phase 255 patients were enrolled, among which 213 were assessable: thereof 48.8% were identified to be at a high risk for relapse following NACT; 86.4% of 81 patients discussed in the molecular tumor board were eligible for a targeted therapy within the interventional multiarm phase II trial COGNITION-GUIDE (Genomics-guided targeted post neoadjuvant therapy in patients with early breast cancer) starting enrolment in Q4/2022. An in-depth longitudinal analysis at baseline and in residual tumor tissue of 16 patients revealed some cases with clonal evolution but largely stable genetic alterations, suggesting restricted selective pressure of broad-acting cytotoxic neoadjuvant chemotherapies. CONCLUSIONS: While most precision oncology initiatives focus on metastatic disease, the presented concept offers the opportunity to empower novel therapy options for patients with high-risk early breast cancer in the post-neoadjuvant setting within a biomarker-driven trial and provides the basis to test the value of precision oncology in a curative setting with the overarching goal to increase cure rates.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Terapia Neoadjuvante , Recidiva Local de Neoplasia/tratamento farmacológico , Medicina de Precisão , Estudos Prospectivos
8.
Psychooncology ; 20(12): 1292-300, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22114044

RESUMO

BACKGROUND: There is no instrument available in Chinese for assessing psychosocial needs. This study aimed to assess the validity and reliability of the Chinese version of the Supportive Care Needs Survey short form (SCNS-SF34-C) in Chinese women with breast cancer (BC). METHODS: The Chinese version of the 34-item SCNS-SF34-C, a self-report measure for assessing psychosocial unmet needs, was administered to 348 Chinese women with BC at the outpatient oncology unit. Exploratory factor analysis (EFA) tested the factor structure. The internal consistency, convergent, divergent, and discriminant validity of the identified factor structure were assessed. RESULTS: In contrast to the five-factor structure identified in the original 34-item SCNS-SF34, our EFA produced a 33-item solution accounting for 54% of score variance comprising four-factors: (1) Health system, information, and patient support, (2) Psychological needs, (3) Physical and daily living, and (4) Sexuality needs. Separate dimensions for Health system and information, and the Patient care and support domains were not supported. Cronbach alphas ranged from 0.75 to 0.92. Correlations of psychological and physical symptom distress measures indicated acceptable convergent validity. No correlation with optimism and positive affect measures indicated divergent validity. Discriminant validity was demonstrated by effective differentiation between clinically distinct patient groups (no active treatment versus active treatment; advanced BC versus localized BC). DISCUSSION: The Chinese version of the Supportive Care Needs Survey has suitable factor structure and psychometric properties for use in assessing psychosocial needs among Chinese women with BC. Further validation is needed for other cancer types.


Assuntos
Neoplasias da Mama/psicologia , Inquéritos e Questionários/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/terapia , China , Análise Fatorial , Feminino , Humanos , Pessoa de Meia-Idade , Avaliação das Necessidades , Psicologia , Reprodutibilidade dos Testes , Tradução
9.
J Vet Pharmacol Ther ; 34(2): 120-9, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21395602

RESUMO

Hepatocytes are highly susceptible to cytokine stimulation and are fundamental to liver function. We established primary canine hepatocyte cultures to study effects of anti-inflammatory agents with hepatoprotective properties. Hepatocyte cultures were incubated with control media alone, silybin (SB), or the more bioavailable silybin-phosphatidylcholine complex (SPC), followed by activation with interleukin-1 beta (IL-1ß; 10 ng/mL). Inflammatory response was measured by prostaglandin E2 (PGE(2) ), interleukin-8 (IL-8), and monocyte chemotactic protein-1 (MCP-1) production and also nuclear factor-kappa B (NF-κB) translocation. Hepatocyte cultures continued production of the phenotypic marker albumin for more than 7 days in culture. IL-1ß exposure increased PGE(2) , IL-8, and MCP-1 production, which was paralleled by NF-κB translocation from the cytoplasm to the nucleus. Pretreatment with SB and SPC significantly inhibited IL-1ß-induced production of pro-inflammatory markers and attenuated NF-κB nuclear translocation. We demonstrate for the first time that primary canine hepatocyte cultures can be maintained in culture without phenotypic loss. The observation that hepatocyte cultures respond to pro-inflammatory IL-1ß activation indicates hepatocytes as primary cellular targets of extrinsic IL-1ß. The ability of SB and SPC to inhibit hepatocyte culture activation by IL-1ß reinforces the notion of their hepatoprotective effects. Our primary canine hepatocyte culture model facilitates identification of hepatoprotective agents and their mechanism of action.


Assuntos
Antioxidantes/farmacologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Interleucina-1beta/antagonistas & inibidores , Silimarina/farmacologia , Animais , Células Cultivadas , Quimiocina CCL2/metabolismo , Dinoprostona/metabolismo , Cães , Interleucina-8/metabolismo , NF-kappa B/metabolismo , Silibina
10.
Proc Inst Mech Eng H ; 225(10): 972-85, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22204119

RESUMO

Bone surrogates are proposed alternatives to human cadaveric vertebrae for assessing interbody device subsidence. A synthetic vertebra with representations of cortices, endplates and cancellous bone was recently developed as an alternative surrogate to polyurethane foam blocks. The ability of the two surrogates to replicate subsidence has not been fully assessed, and was evaluated by indenting them with ring-shaped indenters and comparing their performance with human cadaveric vertebrae using qualitative characteristics and indentation metrics. The sensitivity of each surrogate to a centrally or peripherally placed indenter was of particular interest. Many indentation characteristics of the foam blocks were similar to those of human cadaveric vertebrae, except their insensitivity to centrally and peripherally placed indenters, owing to their homogeneous mechanical properties. This is distinctly different from the cadaveric vertebrae, where a peripherally placed indenter indented significantly less than a centrally placed indenter, because of endplates. By contrast, the synthetic vertebra was sensitive to peripherally placed indenters owing to its bi-material composition, including a thickened peripheral endplate. However, an overly strong synthetic endplate resulted in unrepresentative indentation shape and depth. Both surrogates produced similar results to human cadaveric vertebrae in certain respects, but neither is accurate enough in terms of material property distribution to model subsidence completely in human cadaveric vertebrae.


Assuntos
Substitutos Ósseos/análise , Vértebras Lombares/cirurgia , Próteses e Implantes , Cadáver , Humanos , Vértebras Lombares/fisiopatologia , Teste de Materiais/métodos , Poliuretanos
11.
Osteoarthritis Cartilage ; 18(2): 220-7, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19748608

RESUMO

OBJECTIVE: To evaluate the anti-inflammatory effect of the combination of avocado soybean unsaponifiables (ASU) and epigallocatechin gallate (EGCG) on cyclooxygenase-2 (COX-2) expression and prostaglandin E(2) (PGE(2)) production in cytokine-activated equine chondrocytes. METHODS: Production of type II collagen and aggrecan was verified by immunohistochemistry and Western blot. Chondrocytes were incubated with: (1) control media alone, (2) ASU (4 microg/ml; 8.3 microg/ml), (3) EGCG (4, 40, 400 ng/ml), or (4) the combination of ASU and EGCG for 24h. Cells were next incubated with control medium alone or with IL-1beta (10 ng/ml) and TNF-alpha (1 ng/ml). COX-2 gene expression by real-time PCR analysis and NF-kappaB nuclear translocation by immunohistochemistry were performed after 1h of incubation. PGE(2) production was determined by immunoassay after 24h of incubation. RESULTS: Equine chondrocytes responded to cytokine activation by up-regulated gene expression of COX-2 and increased PGE(2) production. Activation was associated with NF-kappaB translocation. Individually, ASU and EGCG marginally inhibited COX-2 expression and PGE(2) production in activated chondrocytes. In contrast, the combination of ASU and EGCG reduced COX-2 expression close to non-activated control levels and significantly inhibited PGE(2) production. These reductions were statistically greater than those of ASU or EGCG alone. The inhibition of COX-2 expression and PGE(2) production was associated with inhibition of NF-kappaB translocation. CONCLUSION: The present study demonstrates that the anti-inflammatory activity of ASU and EGCG is potentiated when used in combination. This combination may offer an attractive supplement or alternative to non-steroidal anti-inflammatory drugs (NSAIDs) in the management of osteoarthritis.


Assuntos
Catequina/análogos & derivados , Condrócitos/metabolismo , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Glycine max , Persea , Extratos Vegetais/farmacologia , Agrecanas/metabolismo , Animais , Antioxidantes , Cartilagem Articular/enzimologia , Cartilagem Articular/metabolismo , Catequina/farmacologia , Condrócitos/enzimologia , Colágeno Tipo II/metabolismo , Ciclo-Oxigenase 2/genética , Dinoprostona/genética , Modelos Animais de Doenças , Expressão Gênica , Cavalos , Interleucina-1beta/farmacologia , NF-kappa B/metabolismo , Fenótipo , Reação em Cadeia da Polimerase , RNA/análise , Fator de Necrose Tumoral alfa/farmacologia
13.
Br J Pharmacol ; 151(7): 987-97, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17558433

RESUMO

BACKGROUND AND PURPOSE: Statins (3-hydroxy-3-methyl-glutaryl coenzyme A (HMG CoA) reductase inhibitors) have been demonstrated to reduce cardiovascular mortality. It is unclear how the expression level of HMG CoA reductase in cardiovascular tissues compares with that in cells derived from the liver. We hypothesized that this enzyme exists in different cardiovascular tissues, and simvastatin modulates the vascular iberiotoxin-sensitive Ca2+-activated K(+) (BK(Ca)) channels. EXPERIMENTAL APPROACHES: Expression of HMG CoA reductase in different cardiovascular preparations was measured. Effects of simvastatin on BK(Ca) channel gatings of porcine coronary artery smooth muscle cells were evaluated. KEY RESULTS: Western immunoblots revealed the biochemical existence of HMG CoA reductase in human cardiovascular tissues and porcine coronary artery. In porcine coronary artery smooth muscle cells, extracellular simvastatin (1, 3 and 10 microM) (hydrophobic), but not simvastatin Na+ (hydrophilic), inhibited the BK(Ca) channels with a minimal recovery upon washout. Isopimaric acid (10 microM)-mediated enhancement of the BK(Ca) amplitude was reversed by external simvastatin. Simvastatin Na+ (10 microM, applied internally), markedly attenuated isopimaric acid (10 microM)-induced enhancement of the BK(Ca) amplitude. Reduced glutathione (5 mM; in the pipette solution) abolished simvastatin -elicited inhibition. Mevalonolactone (500 microM) and geranylgeranyl pyrophosphate (20 microM) only prevented simvastatin (1 and 3 microM)-induced responses. simvastatin (10 microM ) caused a rottlerin (1 microM)-sensitive (cycloheximide (10 microM)-insensitive) increase of PKC-delta protein expression. CONCLUSIONS AND IMPLICATIONS: Our results demonstrated the biochemical presence of HMG CoA reductase in different cardiovascular tissues, and that simvastatin inhibited the BK(Ca) channels of the arterial smooth muscle cells through multiple intracellular pathways.


Assuntos
Músculo Liso Vascular/efeitos dos fármacos , Peptídeos/farmacologia , Canais de Potássio Cálcio-Ativados/antagonistas & inibidores , Sinvastatina/farmacologia , Adulto , Idoso , Animais , Western Blotting , Caveolina 1/biossíntese , Linhagem Celular , Linhagem Celular Tumoral , Vasos Coronários/citologia , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/fisiologia , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Imidazóis/farmacologia , Técnicas In Vitro , Masculino , Potenciais da Membrana/efeitos dos fármacos , Pessoa de Meia-Idade , Músculo Liso Vascular/citologia , Músculo Liso Vascular/fisiologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/fisiologia , Ésteres de Forbol/farmacologia , Canais de Potássio Cálcio-Ativados/metabolismo , Canais de Potássio Cálcio-Ativados/fisiologia , Proteína Quinase C-delta/metabolismo , Piridinas/farmacologia , Sinvastatina/química , Suínos
14.
AJNR Am J Neuroradiol ; 27(6): 1288-91, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16775281

RESUMO

BACKGROUND: Endoscopic guided biopsy (EGB) is performed after an initial endoscopy for the investigation of patients with suspected nasopharyngeal carcinoma (NPC). The aim of the study was to determine whether MR imaging has the potential to replace invasive EGB in patients with a normal endoscopy. PATIENTS AND METHODS: Data from 2 groups of patients was reviewed, group 1 with proved NPC for MR staging (n = 456) and group 2 with suspected NPC (n = 77). The sensitivity was calculated for group 1 and sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for group 2. RESULTS: In group 1, which included 118 of 456 (26%) with stage 1 disease, cancer was detected in all patients, giving a sensitivity of 100%. In group 2, MR imaging was negative for NPC in 70 (91%) patients, and no cancer has been detected on follow-up (follow-up range, 1-90 months; mean, 36 months). MR imaging was positive for NPC in 7 (9%) patients and NPC was confirmed by biopsy in 3 (4%). Two of these 3 patients had undergone negative endoscopy and biopsy before the MR imaging. NPC was not present in the remaining 4 patients, 2 of whom were found to have lymphoid hyperplasia. MR imaging had a sensitivity of 100%, specificity of 95%, NPV of 100%, PPV of 43%, and accuracy of 95%. CONCLUSION: MR imaging has the potential to screen healthy patients who do not require EGB and direct the site of biopsy in small cancers that may be missed by endoscopy. On the basis of these results, a prospective study is planned.


Assuntos
Carcinoma/diagnóstico , Imageamento por Ressonância Magnética , Neoplasias Nasofaríngeas/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Carcinoma/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/patologia , Nasofaringe/patologia , Sensibilidade e Especificidade
15.
Biochim Biophys Acta ; 677(1): 153-9, 1981 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-7295788

RESUMO

The adult rat lung supernatant contains some factors which markedly enhance adenylate cyclase activity in membranes (Nijjar, M.S. (1979) Biochim. Biophys. Acta 584, 43-50). These factors were separated into two less active components (peaks 1 and 2) by DEAE-cellulose chromatography. However, their recombination restored the full activation of adenylate cyclase. Further purification and characterization of these factors revealed that the activator in peak 1 contained two proteins of low (14 500) and high (65 000) molecular weight whereas the activator in peak 2 contained only one protein of 65 000. The kinetics of adenylate cyclase activation revealed that both the Km and V values were affected. The data also demonstrate that calmodulin was not involved in the cytoplasmic activation of adenylate cyclase in rat lungs.


Assuntos
Adenilil Ciclases/metabolismo , Citoplasma/análise , Pulmão/enzimologia , Proteínas/isolamento & purificação , Animais , Membrana Celular/enzimologia , Cromatografia DEAE-Celulose , Ativação Enzimática , Cinética , Masculino , Peso Molecular , Ratos , Ratos Endogâmicos
16.
Circulation ; 104(18): 2236-41, 2001 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-11684637

RESUMO

BACKGROUND: Radioactive stents have been reported to reduce in-stent neointimal thickening. An unexpected increase in neointimal response was observed, however, at the stent-to-artery transitions, the so-called "edge effect." To investigate the factors involved in this edge effect, we studied stents with 1 radioactive half and 1 regular nonradioactive half, thereby creating a midstent radioactive dose-falloff zone next to a nonradioactive stent-artery transition at one side and a radioactive stent-artery transition at the other side. METHODS AND RESULTS: Half-radioactive stents (n=20) and nonradioactive control stents (n=10) were implanted in the coronary arteries of Yucatan micropigs. Animals received aspirin and clopidogrel as antithrombotics. After 4 weeks, a significant midstent stenosis was observed by angiography in the half-radioactive stents. Two animals died suddenly because of coronary occlusion at this mid zone at 8 and 10 weeks. At 12-week follow-up angiography, intravascular ultrasound and histomorphometry showed a significant neointimal thickening at the midstent dose-falloff zone of the half-radioactive stents, but not at the stent-to-artery transitions at both extremities. Such a midstent response (mean angiographic late loss 1.0 mm) was not observed in the nonradioactive stents (mean loss 0.4 to 0.6 mm; P< 0.01). CONCLUSIONS: The edge effect of high-dose radioactive stents in porcine coronary arteries is associated with the combination of stent injury and radioactive dose falloff.


Assuntos
Vasos Coronários/efeitos da radiação , Oclusão de Enxerto Vascular/etiologia , Oclusão de Enxerto Vascular/prevenção & controle , Radioisótopos de Fósforo/administração & dosagem , Stents/efeitos adversos , Animais , Implante de Prótese Vascular , Angiografia Coronária , Vasos Coronários/patologia , Vasos Coronários/cirurgia , Modelos Animais de Doenças , Progressão da Doença , Relação Dose-Resposta à Radiação , Implantes de Medicamento , Feminino , Oclusão de Enxerto Vascular/patologia , Implantes Experimentais , Porco Miniatura , Túnica Íntima/patologia , Túnica Íntima/efeitos da radiação , Grau de Desobstrução Vascular/efeitos da radiação
17.
Integr Biol (Camb) ; 7(10): 1120-34, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25959051

RESUMO

Tumors are stiff and data suggest that the extracellular matrix stiffening that correlates with experimental mammary malignancy drives tumor invasion and metastasis. Nevertheless, the relationship between tissue and extracellular matrix stiffness and human breast cancer progression and aggression remains unclear. We undertook a biophysical and biochemical assessment of stromal-epithelial interactions in noninvasive, invasive and normal adjacent human breast tissue and in breast cancers of increasingly aggressive subtype. Our analysis revealed that human breast cancer transformation is accompanied by an incremental increase in collagen deposition and a progressive linearization and thickening of interstitial collagen. The linearization of collagen was visualized as an overall increase in tissue birefringence and was most striking at the invasive front of the tumor where the stiffness of the stroma and cellular mechanosignaling were the highest. Amongst breast cancer subtypes we found that the stroma at the invasive region of the more aggressive Basal-like and Her2 tumor subtypes was the most heterogeneous and the stiffest when compared to the less aggressive luminal A and B subtypes. Intriguingly, we quantified the greatest number of infiltrating macrophages and the highest level of TGF beta signaling within the cells at the invasive front. We also established that stroma stiffness and the level of cellular TGF beta signaling positively correlated with each other and with the number of infiltrating tumor-activated macrophages, which was highest in the more aggressive tumor subtypes. These findings indicate that human breast cancer progression and aggression, collagen linearization and stromal stiffening are linked and implicate tissue inflammation and TGF beta.


Assuntos
Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Fenômenos Biomecânicos , Fenômenos Biofísicos , Birrefringência , Neoplasias da Mama/fisiopatologia , Carcinoma Intraductal não Infiltrante/imunologia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/fisiopatologia , Transformação Celular Neoplásica , Colágeno/metabolismo , Progressão da Doença , Matriz Extracelular/fisiologia , Feminino , Humanos , Macrófagos/imunologia , Macrófagos/patologia , Microscopia de Força Atômica , Microscopia de Fluorescência por Excitação Multifotônica , Invasividade Neoplásica/imunologia , Invasividade Neoplásica/patologia , Invasividade Neoplásica/fisiopatologia , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo
18.
Pain ; 89(2-3): 245-52, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11166481

RESUMO

In the present study, we examined whether fear of pain, dental fear, general indices of psychological distress, and self-reported stress levels differed between 40 orofacial pain patients and 40 gender and age matched control general dental patients. We also explored how fear of pain, as measured by the Fear of Pain Questionnaire-III (J Behav Med 21 (1998) 389), relates to established measures of psychological problems in our sample of patients. Finally, we examined whether fear of pain uniquely and significantly predicts dental fear and psychological distress relative to other theoretically-relevant psychological factors. Our results indicate that fear of severe pain and anxiety-related distress, broadly defined, are particularly elevated in orofacial pain patients relative to matched controls. Additionally, fear of pain shares a significant relation with dental fear but not other general psychological symptomology, and uniquely and significantly predicts dental fear relative to other theoretically-relevant variables. Taken together, these data, in conjunction with other recent studies, suggest greater attention be placed on understanding the fear of pain in orofacial pain patients and its relation to dental fear and anxiety.


Assuntos
Dor Facial/psicologia , Medo/psicologia , Dor/psicologia , Adulto , Ansiedade ao Tratamento Odontológico/psicologia , Depressão/psicologia , Feminino , Humanos , Masculino , Medição da Dor , Escalas de Graduação Psiquiátrica , Estresse Psicológico/fisiopatologia , Estresse Psicológico/psicologia , Inquéritos e Questionários
19.
Int J Radiat Oncol Biol Phys ; 51(4): 1058-63, 2001 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-11704331

RESUMO

BACKGROUND: The major limitation of coronary stenting remains in-stent restenosis, due to the development of neointimal proliferation. Radioactive stents have demonstrated the ability to reduce this proliferation in the healthy nonatherosclerotic porcine animal model. However, inhibition of tissue proliferation in the in-stent restenotic lesion in a porcine model is not well characterized. The objective of this study was to examine the efficacy and safety of the 32P radioactive stent for the treatment of in-stent restenosis in a double stent injury model of the porcine coronaries. METHODS AND MATERIALS: Eighteen coronary arteries in 9 pigs underwent nonradioactive stent (8 mm in length) implantation. Thirty days after the initial stent implantation, a 32P radioactive stent (18 mm in length) with an activity of 0 and 18 microCi was implanted to cover the initial stent. The swine were killed 30 days after the second stent implantation. Histomorphometric analysis was performed for vessel area (VA), stent strut area (SSA), intimal area (IA), and lumen area (LA). RESULTS: Injury scores, VA, SSA, and LA were similar among the control and radiated groups. Neointimal formation was significantly reduced after placement of radioactive stents as compared to control in both the overlapped (0.93 +/- 0.12 vs. 1.31 +/- 0.51 mm(2), p < 0.05) and nonoverlapped segments (1.14 +/- 0.21 vs. 1.91 +/- 1.04 mm(2), p < 0.05). The smooth muscle cell index in the neointima was reduced. Intimal fibrin was increased in the radiated group as compared to the control (p < 0.01 respectively). CONCLUSIONS: 32P radioactive stents may be safe and effective in reducing neointimal formation leading to in-stent restenosis. Longer follow-up will be required to examine whether these positive findings can be maintained.


Assuntos
Reestenose Coronária/prevenção & controle , Radioisótopos de Fósforo/uso terapêutico , Stents , Animais , Reestenose Coronária/patologia , Suínos , Túnica Íntima/efeitos da radiação
20.
Obstet Gynecol ; 87(5 Pt 2): 826-9, 1996 May.
Artigo em Inglês | MEDLINE | ID: mdl-8677103

RESUMO

BACKGROUND: Peripartum pubic symphyseal rupture is diagnosed on clinical grounds. Although the diagnosis may be supported by radiography, which shows diastasis of the pubic rami, magnetic resonance imaging (MRI) can visualize the nature of the soft tissue injury. CASE: Two puerperas thought clinically to have pubic symphyseal rupture were imaged with MRI. In addition to diastasis of the pubic rami, clefts were seen within the symphyseal cartilage, extending the entire breadth of the joint. The clefts were filled with fluid or hemorrhage, seen in T1- and T2-weighted images. The fluid was encapsulated within the joint by the surrounding ligaments. Four control normal puerperas, who had vaginal deliveries but were asymptomatic, showed none of the aforementioned findings. CONCLUSION: MRI can visualize the soft tissue injury seen in pubic symphyseal rupture and may be used to confirm the clinical diagnosis.


Assuntos
Sínfise Pubiana/lesões , Transtornos Puerperais/diagnóstico , Adulto , Estudos de Casos e Controles , Parto Obstétrico , Feminino , Humanos , Imageamento por Ressonância Magnética , Gravidez , Transtornos Puerperais/etiologia , Ruptura Espontânea , Lesões dos Tecidos Moles/diagnóstico , Lesões dos Tecidos Moles/etiologia
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