Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 40
Filtrar
Mais filtros

Bases de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Dig Dis Sci ; 63(2): 422-428, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29302875

RESUMO

BACKGROUND: During capsule endoscopy (CE) studies, the complete examination rate (CER) can be increased by prolonging capsule battery life or reducing gastric transit time (GTT) and/or small bowel transit time (SBTT). However, despite enhanced battery life, 10% of studies remain incomplete. Previously studied interventions to reduce SBTT and enhance CER have produced conflicting results. We hypothesize that this may be a consequence of an insufficiently potent stimulus of small bowel motility. AIMS: To examine whether potent stimulation of the cephalic response of digestion during small bowel CE reduces GTT and/or SBTT and thus increases the CER. METHODS: A single-blind randomized trial was performed to evaluate the effect of bacon sham feeding on GTT, SBTT and CER. RESULTS: Baseline characteristics were similar between 63 sham fed patients and 59 controls. The median GTT was 17 min (9-65) in the bacon group and 25 min (14-55) in the control group. The median SBTT was 199 min (119-316) and 222 min (151-287), respectively. Cox proportional hazards model demonstrated no significant difference between groups for GTT (rate ratio 1.03, 95% CI 0.71-1.51, P = 0.87) or SBTT (rate ratio 1.02, 95% CI 0.70-1.49, P = 0.93). Although the taste of bacon was considered favorably by 72% of participants, taste did not correlate with GTT (ρ = 0.03, P = 0.83) or SBTT (ρ = - 0.115, P = 0.33). The CER was 91 and 95% in the bacon and control groups, respectively (P = 0.35). CONCLUSION: Bacon sham feeding has no effect on GTT, SBTT or CER and cannot be recommended in clinical practice.


Assuntos
Endoscopia por Cápsula/métodos , Trânsito Gastrointestinal , Produtos da Carne , Animais , Digestão/fisiologia , Feminino , Motilidade Gastrointestinal , Humanos , Intestino Delgado , Masculino , Estômago , Suínos
2.
Hemoglobin ; 41(1): 21-25, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28532285

RESUMO

Transfusion-dependent hereditary anemias such as ß-thalassemia (ß-thal), predispose patients to iron overload and its numerous clinical sequelae. Accurate assessment of overall iron status and prompt initiation of chelation therapy to prevent irreversible end-organ damage can be achieved using magnetic resonance imaging (MRI) to measure liver iron concentration (LIC) as a surrogate marker of total body iron; however, its access may be associated with long wait times and delay in treatment. We report an observational cohort study at a single tertiary care center assessing the theoretical role of transient elastography (TE), which measures liver stiffness, in estimating LIC compared to other established diagnostic measures. While regression analyses confirm a moderate correlation between LIC per R2 MRI and serum ferritin level (pooled estimate of correlation = 0.55), there was no significant correlation between TE reading and LIC based on R2 MRI (pooled estimate of correlation = -0.06), and only a weak correlation was observed with serum ferritin level (pooled estimate of correlation = 0.45). These results suggest TE may not be sensitive enough to detect subtle changes in the hepatic parenchymal stiffness associated with liver iron deposition.


Assuntos
Técnicas de Imagem por Elasticidade , Sobrecarga de Ferro/diagnóstico , Sobrecarga de Ferro/metabolismo , Ferro/metabolismo , Fígado/metabolismo , Fígado/patologia , Imageamento por Ressonância Magnética , Adulto , Biomarcadores , Transfusão de Sangue , Feminino , Humanos , Sobrecarga de Ferro/etiologia , Masculino , Estudos Prospectivos , Adulto Jovem
3.
Gastrointest Endosc ; 81(6): 1337-42, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25841579

RESUMO

BACKGROUND AND AIMS: ERCP is an advanced endoscopic procedure that is technically more challenging and carries a higher risk of adverse events compared with standard endoscopy. A discrepancy currently exists among guidelines regarding the number of ERCPs that a trainee needs to complete before procedural competency should be assessed. Our aim was to assess the learning curve for performing ERCP. METHODS: Two authors independently searched MEDLINE (1946 to November 25, 2014) along with the gray literature to identify relevant citations. To warrant inclusion, citations were required to report successful trainee cannulation rate. Successful cannulation rate, set at a value of 80% or higher, was used as our baseline reference for competency. RESULTS: Nine studies, assessing 137 trainees and 17,100 ERCPs, were included in our analysis. Overall, competency was achieved among the included studies between 70 to 400 ERCPs. In the 2 studies that used pancreatic duct cannulation rate, competency was achieved by 70 to 160 ERCPs. Of the 5 studies that used selective duct cannulation rate, competency was achieved by 79 to 300 ERCPs. Finally, in the 4 studies that used common bile duct cannulation rate, 2 studies reached the reference competency threshold by 160 to 400 ERCPs. On further stratification, when assessing native papilla deep common bile duct cannulation, only 1 study reached the reference competency threshold by 350 to 400 ERCPs. CONCLUSIONS: Our findings suggest that as ERCP has evolved from a predominantly diagnostic to therapeutic procedure, procedural thresholds have risen well above North American training guidelines. Therefore, advanced endoscopy training programs need to reassess their current structure to ensure that procedural competency is being reached.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica/normas , Competência Clínica , Endoscopia do Sistema Digestório/educação , Curva de Aprendizado , Bolsas de Estudo , Gastroenterologia/educação , Cirurgia Geral/educação , Humanos , Internato e Residência
4.
Can J Surg ; 58(4): 226-31, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26022155

RESUMO

BACKGROUND: Computed tomography (CT) scans are commonly used to diagnose acute diverticulitis, but there are overlapping features between diverticulitis and colorectal cancer (CRC) on imaging studies. Hence, colonoscopy is typically recommended after an episode of acute diverticulitis to rule out underlying malignancy. Currently, 64-slice multidetector CT scanners are capable of providing higher-resolution images and may be able to distinguish malignancy from diverticular inflammation. We aimed to determine the prevalence of CRC among patients with CT-diagnosed acute diverticulitis. METHODS: We performed a retrospective study of patients with acute diverticulitis diagnosed on CT scan between December 2005 and December 2010 at St. Paul's Hospital, Vancouver, BC. Nonresidents were excluded. We reviewed CT scan reports that included the term "diverticulitis," reports of follow-up colonic evaluation within 1 year of diagnosis and pathology results. We queried the provincial cancer registry to ensure no cases of CRC were missed. RESULTS: A total of 293 patients had acute diverticulitis diagnosed on CT scan, but 8 were nonresidents and were excluded. Of the 285 included in the analysis, the mean age was 59.4 ± 15.1 years, and 167 (58.6%) were men. Among the 114 patients who underwent follow-up evaluation, malignancy was diagnosed in 4 (3.5%). The overall prevalence of malignancy among patients with CT-diagnosed diverticulitis was 1.4%. CONCLUSION: Routine endoscopic evaluation after an episode of diverticulitis diagnosed with high-resolution CT scan does not appear to be necessary. Selective approach in patients with protracted clinical course or those with mass lesion/obstruction on CT scan may be of benefit.


CONTEXTE: La tomodensitométrie (TDM) est couramment utilisée pour le diagnostic de la diverticulite aiguë, mais des caractéristiques sont communes à la diverticulite et au cancer colorectal (CCR) aux épreuves d'imagerie. On recommande donc en général la coloscopie après un épisode de diverticulite aiguë pour écarter un diagnostic de cancer sous-jacent. À l'heure actuelle, les appareils de TDM multidétecteurs à 64 barrettes peuvent fournir des images de haute résolution et permettent même de distinguer le cancer d'une inflammation diverticulaire. Nous avons voulu déterminer la prévalence du CCR chez les patients ayant présenté une diverticulite aiguë diagnostiquée par TDM. MÉTHODES: Nous avons procédé à une étude rétrospective sur des patients porteurs d'une diverticulite aiguë diagnostiquée à l'aide de TDM entre décembre 2005 et décembre 2010 à l'Hôpital St. Paul's de Vancouver, en Colombie-Britannique. Les non-résidents ont été exclus. Nous avons examiné les rapports de TDM incluant le terme « diverticulite ¼, les rapports d'examens du côlon au cours de l'année suivant le diagnostic et les rapports d'anatomopathologie. Nous avons interrogé le registre provincial sur le cancer pour nous assurer qu'aucun cas de CCR ne nous avait échappé. RÉSULTATS: En tout, 293 patients ont reçu un diagnostic de diverticulite à l'aide de la TDM; 8 étaient des non-résidents et ont été exclus. Parmi les 285 patients inclus dans l'analyse, l'âge moyen était de 59,4 ± 15,1 ans et 167 (58,6 %) étaient des hommes. Parmi les 114 patients qui ont subi un examen de suivi, le cancer a été diagnostiqué chez 4 (3,5 %). La prévalence globale du cancer chez les patients porteurs d'un diagnostic de diverticulite posé par TDM était de 1,4 %. CONCLUSION: L'évaluation endoscopique de routine après un épisode de diverticulite diagnostiquée à l'aide d'une TDM de haute résolution ne semble pas nécessaire. Une approche sélective chez les patients qui présentent une évolution clinique lente ou ceux qui présentent une lésion ou obstruction tumorale à la TDM pourrait être utile.


Assuntos
Colonoscopia , Neoplasias Colorretais/diagnóstico , Doença Diverticular do Colo/diagnóstico por imagem , Sistema de Registros/estatística & dados numéricos , Tomografia Computadorizada por Raios X , Adulto , Idoso , Colúmbia Britânica/epidemiologia , Neoplasias Colorretais/epidemiologia , Doença Diverticular do Colo/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos
5.
Biochim Biophys Acta ; 1830(8): 4053-64, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23583370

RESUMO

BACKGROUND: Statins, the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors with cholesterol-lowering properties, were recently shown to exhibit anti-cancer effects. However, the molecular mechanism underlying statin-induced cancer cell death remains to be elucidated. Elevated level of survivin is often found over-expressed in human cancers and has been implicated in the progression of tumorigenesis. Given its central role in cell division and action as an apoptosis suppressor, survivin represents a potential molecular target in cancer management. METHODS: In this study, we explored the underlying mechanisms in simvastatin-induced HCT116 colorectal cancer cell apoptosis. RESULTS: Simvastatin decreased cell viability and induced cell apoptosis in HCT116 cells. These results are associated with the modulation of p21(cip/Waf1) and survivin. Survivin knockdown using survivin siRNAs also decreased cell viability and induced cell apoptosis. Simvastatin's actions on p21(cip/Waf1), survivin and apoptosis were reduced in p53 null HCT116 cells. Simvastatin caused an increase in p53 phosphorylation and acetylation. In addition, simvastatin activated p38 mitogen-activated protein kinase (p38MAPK), whereas an inhibitor of p38MAPK signaling abrogated simvastatin's effects of increasing p53 and p21(cip/Waf1) promoter luciferase activity. Cell viability and survivin promoter luciferase activity in the presence of simvastatin were also restored by p38MAPK inhibitor. Furthermore, Sp1 binding to the survivin promoter region decreased while p53 and p63 binding to the promoter region increased after simvastatin exposure. CONCLUSIONS: Simvastatin activates the p38MAPK-p53-survivin cascade to cause HCT116 colorectal cancer cell apoptosis. GENERAL SIGNIFICANCE: This study delineates, in part, the underlying mechanisms of simvastatin in decreasing survivin and subsequent colorectal cancer cell apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Proteínas Inibidoras de Apoptose/fisiologia , Transdução de Sinais , Sinvastatina/farmacologia , Proteína Supressora de Tumor p53/fisiologia , Proteínas Quinases p38 Ativadas por Mitógeno/fisiologia , Acetilação , Sobrevivência Celular/efeitos dos fármacos , Células HCT116 , Humanos , Proteínas Inibidoras de Apoptose/genética , Regiões Promotoras Genéticas , Survivina , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Angiogenesis ; 17(2): 407-18, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24048742

RESUMO

Formation of lymphatic capillaries by lymphatic endothelial cells (LECs) occurs both in normal tissues as well as in pathological processes including tumor metastasis. Interleukin-6 (IL-6), a potent pro-inflammatory cytokine, has been shown to be highly elevated in various cancers. IL-6 has also been shown to increase tumor lymphangiogenesis through vascular endothelial growth factor-C (VEGF-C) induction in tumor cells. Although lymphangiogenesis is associated with lymph node metastasis and also resistance to conventional therapy in various cancers, the precise mechanisms of lymphangiogenesis in LECs remain unclear. This study aimed to investigate the signaling cascade involved in IL-6-induced VEGF-C expression in murine LECs (SV-LEC). The VEGF-C mRNA and protein levels were increased in SV-LECs exposed to IL-6. IL-6 time-dependently induced Src phosphorylation and downstream phosphorylation of ERK1/2 and p38MAPK. In contrast, PP2, an inhibitor of Src signaling, abrogated IL-6's effects on ERK1/2 and p38MAPK phosphorylation. IL-6 exposure also led to increase in VEGF-C promoter-luciferase activity as well as C/EBPß- and κB-luciferase activities. VEGF-C promoter-, C/EBPß- and κB-luciferase activities were all suppressed by Src, ERK1/2 or p38MAPK signaling blockades despite presence of IL-6. Finally, C/EBPß and p65 binding to the VEGF-C promoter region were increased after IL-6 exposure in SV-LECs. Taken together, we report a Src-mediated ERK1/2 and p38MAPK activation resulting in C/EBPß and p65 binding to the promoter region of VEGF-C, leading to VEGF-C expression in IL-6-exposed SV-LECs.


Assuntos
Células Endoteliais/metabolismo , Interleucina-6/farmacologia , Fator C de Crescimento do Endotélio Vascular/metabolismo , Quinases da Família src/metabolismo , Animais , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Linhagem Celular , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/enzimologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos , Receptores de Interleucina-6/metabolismo , Fator de Transcrição STAT3/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
7.
Gastrointest Endosc ; 79(4): 630-6, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24112594

RESUMO

BACKGROUND: Approximately 1 in 6 capsule endoscopies (CEs) does not visualize the entire small bowel at completion of the examination because of limited battery life. OBJECTIVE: To determine whether chewing gum can reduce the small-bowel transit time and increase CE completion rates. DESIGN: Prospective, single-blind, randomized, controlled trial. SETTING: A tertiary university-affiliated hospital. PATIENTS: Consecutive patients 19 years of age and older undergoing outpatient small-bowel CE from October 2010 to July 2012 were assessed for eligibility. Those with previous gastric or small-bowel surgery or ileostomy, dysphagia prohibiting capsule ingestion, diabetes mellitus with evidence of end-organ damage, use of narcotics or prokinetics within 5 days before the procedure, clinical hyper-/hypothyroidism, and symptoms suggestive of acute bowel obstruction were excluded. INTERVENTION: Gum chewing for at least 20 minutes every 2 hours starting at the time of capsule ingestion. MAIN OUTCOME MEASUREMENTS: Small-bowel transit time, gastric transit time, and completion rate were measured. RESULTS: Chewing gum did not have any significant effect on gastric transit time (rate ratio 1.06; 95% CI, 0.73-1.55; P = .75), small-bowel transit time (rate ratio 0.91; 95% CI, 0.62-1.35; P = .65), or completion rate (91.67% chewing gum vs 88.71% control, P = .58) of CE. LIMITATION: Single-center study involving relatively healthy subjects. Procedures were done on an outpatient basis so participants were not monitored for adherence to protocol. CONCLUSIONS: Chewing gum does not speed up capsule transit or increase completion rate of CE in patients without risk factors for incomplete studies. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01241825.).


Assuntos
Endoscopia por Cápsula , Goma de Mascar , Trânsito Gastrointestinal , Intestino Delgado/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peristaltismo , Estudos Prospectivos , Método Simples-Cego
8.
Gastrointest Endosc ; 79(3): 408-416.e4, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24206747

RESUMO

BACKGROUND: Low-volume bowel preparations are ideal to ensure patient compliance, thus enabling high-quality examinations to be achieved. OBJECTIVES: To examine the bowel-cleansing efficacy and patient tolerability of split-dose 2 L PEG3350 + electrolytes (PEG3350e) with 15 mg bisacodyl versus split-dose 4 L PEG3350e. DESIGN: Single-blinded, noninferiority, randomized, controlled trial. SETTING: Single site, university-affiliated tertiary care center. PATIENTS: A total of 325 consecutive patients undergoing elective outpatient colonoscopy. INTERVENTION: 2 L of PEG3350e with 15 mg bisacodyl versus 4 L of PEG3350e, both given in a split-dose fashion. MAIN OUTCOME MEASUREMENTS: Efficacy and tolerability of a split dose of 2 L of PEG3350e with 15 mg bisacodyl. Efficacy was assessed by using the Boston Bowel Preparation Scale and Ottawa Bowel Preparation Scale. Patient satisfaction and tolerability were assessed by using a short survey. RESULTS: A total of 325 patients were included in the intention-to-treat analysis (51% male) with a mean ± standard deviation age of 56 ± 11.2 years. No statistically significant difference in cleanliness was found by using the Boston Bowel Preparation Scale (intention-to-treat, P = .381; per-protocol, P = .387) and the Ottawa Bowel Preparation Scale (intention-to-treat, P = .285; per-protocol, P = .334). Participants receiving 2 L of PEG3350e found the preparation easy to consume and were willing to repeat the procedure more often than the 4-L group (P < .001). LIMITATIONS: Single-center study looking at outpatient colonoscopies; unable to comment on adenoma detection rate. CONCLUSIONS: Bowel-cleansing efficacy was similar in both the 2-L and 4-L PEG3350e groups; however, patient tolerability and willingness to repeat preparation were statistically greater with the 2 L of PEG3350e with 15 mg bisacodyl regimen.


Assuntos
Catárticos/administração & dosagem , Colonoscopia/métodos , Polietilenoglicóis/administração & dosagem , Adulto , Idoso de 80 Anos ou mais , Bisacodil/administração & dosagem , Catárticos/efeitos adversos , Eletrólitos/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Polietilenoglicóis/efeitos adversos , Método Simples-Cego , Adulto Jovem
9.
Gastrointest Endosc ; 80(2): 277-83, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24629419

RESUMO

BACKGROUND: High-quality colonoscope withdrawal technique is associated with a higher adenoma detection rate. Position change is routinely used in barium enema and CT colonography to facilitate adequate distension of the colon and promote movement of fluid from the segment of the colon being assessed. OBJECTIVE: To determine whether prescribed position changes during colonoscope withdrawal affect the adenoma detection rate compared with the usual care per endoscopist. DESIGN: Prospective, randomized, controlled trial. SETTING: Tertiary-care, university-affiliated hospital. PATIENTS: Patients referred for outpatient colonoscopy between July 2011 and July 2012 were evaluated for eligibility. Inclusion criteria were outpatient status and age ≥40 years. Exclusion criteria were (1) complete colonoscopy within 1 year before the procedure, (2) inability to provide informed consent, (3) incomplete colonoscopy to the cecum, (4) previous bowel resection, (5) inflammatory bowel disease, (6) colonic polyposis syndrome, (7) inadequate bowel preparation, and (8) musculoskeletal disorder or other mobility issues limiting effective patient position changes during colonoscopy. INTERVENTIONS: Prescribed position changes during colonoscope withdrawal. MAIN OUTCOME MEASUREMENTS: Polyp detection rate (PDR) and adenoma detection rate (ADR). RESULTS: A total of 776 patients were enrolled, with 388 in the dynamic group. There was no difference in PDR (odds ratio [OR] 0.99; P = .93) or ADR (OR 1.17; P = .28). Colonoscope withdrawal time was longer in the dynamic group (median time 466.5 vs 422.5 seconds; P < .0001). LIMITATIONS: Single-center study. Indication for procedure not controlled. Lack of standardized bowel preparation and blinding. CONCLUSION: Prescribed position changes during colonoscope withdrawal do not affect polyp/adenoma detection compared with the usual practice when the baseline ADR is above the recommended standard. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01395173.).


Assuntos
Adenoma/diagnóstico , Pólipos do Colo/diagnóstico , Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico , Posicionamento do Paciente , Idoso , Colonoscópios , Remoção de Dispositivo , Feminino , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo
10.
Biochim Biophys Acta ; 1820(2): 104-15, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22155142

RESUMO

BACKGROUND: Elevated levels of survivin and histone deacetylases (HDACs) are often found over-expressed in human cancers, including colorectal cancer, and have been implicated in tumorigenesis. HDAC inhibition induces growth arrest and cell death in various transformed cell; however, the mechanisms by which this reduces cell viability in colorectal cancer cells remain unexplained. METHODS: We explored the actions of two HDAC inhibitors, trichostatin A (TSA) and sirtinol, in HT29 colon cancer cells. RESULTS: TSA and sirtinol induced apoptosis and inhibited cell proliferation in HT29 cells. These results are associated with the modulation of survivin. Survivin promoter luciferase activity and Sp1, a transcription factor that contributes to survivin expression, were suppressed in cells exposed to TSA or sirtinol. TSA and sirtinol also activated p38 mitogen-activated protein kinase (p38MAPK) and AMP-activated protein kinase (AMPK). Inhibitors of p38MAPK or AMPK signaling abrogated TSA and sirtinol's effects of decreasing cell viability. Survivin promoter luciferase activity in the presence of TSA or sirtinol was restored by AMPK dominant negative mutant or p38MAPK inhibitor. Furthermore, Sp1 binding to the survivin promoter region decreased while p63 binding to the promoter region increased after TSA or sirtinol exposure. CONCLUSIONS: We report a p38MAPK- and AMPK-mediated downregulation of survivin, and its functional correlation with decreased colon cancer cell viability in the presence of HDAC inhibitor. p63 and Sp1 may also contribute to TSA and sirtinol actions. GENERAL SIGNIFICANCE: This study delineates, in part, the underlying mechanisms of TSA and sirtinol in decreasing survivin expression and subsequent colon cancer cell viability.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Benzamidas/farmacologia , Neoplasias do Colo/enzimologia , Ácidos Hidroxâmicos/farmacologia , Proteínas Inibidoras de Apoptose/metabolismo , Naftóis/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HT29 , Humanos , Proteínas Inibidoras de Apoptose/genética , Luciferases/metabolismo , Plicamicina/análogos & derivados , Plicamicina/farmacologia , Regiões Promotoras Genéticas/genética , Ligação Proteica/efeitos dos fármacos , Fator de Transcrição Sp1/metabolismo , Survivina , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo
11.
Biochim Biophys Acta ; 1810(12): 1160-9, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21911040

RESUMO

BACKGROUND: Histone deacetylase (HDAC) inhibitors have emerged as a new class of antitumor agents because they were demonstrated to induce cell cycle arrest, promote cell apoptosis, and inhibit metastasis. Recently, HDAC inhibitors were also shown to exhibit pronounced anti-inflammatory properties. However, the underlying mechanism contributing to the suppression of inflammatory responses by HDAC inhibitors remains to be fully defined. In the present study, we explored the actions of trichostatin A (TSA), a potent HDAC inhibitor, on lipopolysaccharide (LPS)-induced cyclooxygenase (COX)-2 expression in human umbilical vascular endothelial cells (HUVECs). METHODS: HUVECs were exposed to LPS in the absence or presence of TSA. COX-2 expression and signaling molecules (JNK, p38MAPK and c-jun) activated by LPS were assessed. RESULTS: The LPS-induced cox-2 messenger RNA and protein were markedly suppressed by TSA. TSA inhibited JNK and p38MAPK phosphorylation in cells exposed to LPS. Treatment of cells with a JNK signaling inhibitor (JNK inhibitor II) or a p38MAPK inhibitor (p38MAPK inhibitor III) markedly inhibited LPS-induced COX-2 expression. TSA suppression of JNK and p38MAPK phosphorylation and subsequent COX-2 expression were restored by selective inhibition of MKP-1 using MKP-1 siRNA. In addition, TSA caused an increase in MKP-1 phosphatase activity in HUVECs. In conclusion, TSA may cause MKP-1 activation to dephosphorylate JNK and p38MAPK, leading to the downregulation of COX-2 in HUVECs stimulated by LPS, a proinflammatory stimulus. GENERAL SIGNIFICANCE: MKP-1 contributes to TSA's protective actions in HUVECs exposed to LPS. The present study also supports the therapeutic value of TSA in treating inflammatory vascular diseases.


Assuntos
Inibidores de Ciclo-Oxigenase 2/farmacologia , Ciclo-Oxigenase 2/efeitos dos fármacos , Fosfatase 1 de Especificidade Dupla/metabolismo , Endotélio Vascular/efeitos dos fármacos , Ácidos Hidroxâmicos/farmacologia , Veias Umbilicais/efeitos dos fármacos , Sequência de Bases , Western Blotting , Células Cultivadas , Ciclo-Oxigenase 2/metabolismo , Primers do DNA , Endotélio Vascular/citologia , Endotélio Vascular/enzimologia , Humanos , Fosforilação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Veias Umbilicais/citologia , Veias Umbilicais/enzimologia
12.
Clin Gastroenterol Hepatol ; 10(12): 1381-5, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22975384

RESUMO

BACKGROUND & AIMS: Capsule endoscopy (CE) is used most frequently to identify causes of obscure gastrointestinal bleeding (OGIB). Identifying factors associated with the detection of lesions by CE could improve resource utilization and thereby improve patient selection for CE examination. We sought to identify clinical factors associated with positive findings from CE in patients with OGIB. METHODS: We analyzed data from 698 CE procedures performed between December 2001 and April 2011 at St Paul's Hospital, Vancouver, Canada (50.3% of patients were female; mean age, 63.4 years). A positive finding was defined as a lesion that was believed to be the source of the bleeding (ulceration, mass lesion, vascular lesion, or visible blood). Univariate and multivariate logistic regression analyses were used to correlate demographic and clinical parameters with positive findings. RESULTS: A lesion believed to be the cause of bleeding was identified in 42% of cases. In univariate analysis, the number of esophagogastroduodenoscopies (EGDs), the presence of connective tissue disease or diabetes with end-organ damage, Charlson comorbidity index scores, and increasing transfusion requirements were significantly associated with identification of causative pathology from CE (all P < .027). In multivariate analysis, increasing number of EGDs (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.00-1.37), increasing transfusion requirements (3-9 units: OR, 1.70; 95% CI, 1.08-2.66, and ≥10 units: OR, 2.72; 95% CI, 1.69-4.37), and connective tissue disease (OR, 2.24; 95% CI, 1.14-4.41) were all significantly associated with identification of positive findings by using CE (all P < .045). CONCLUSIONS: Patients with a higher number of precapsule EGDs or transfusions, or connective tissue disease, are superior candidates for analysis of OGIB by CE.


Assuntos
Endoscopia por Cápsula/métodos , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Sangue Oculto , Idoso , Canadá , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
Can J Gastroenterol ; 26(10): 687-90, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23061059

RESUMO

BACKGROUND: The diagnostic yield of capsule endoscopy (CE) in the setting of iron deficiency anemia (IDA) without evidence of occult/overt bleeding has been questioned. Often, these patients have nongastrointestinal causes of iron deficiency but undergo CE to exclude a potential small bowel source. OBJECTIVE: To assess the diagnostic yield of CE, the characteristics predicting positive results, the presumed etiology of IDA in negative/normal CE and patient management after CE. METHODS: A retrospective review of 934 patients who underwent CE between December 2001 and February 2010 was conducted. All patients had undergone previous negative endoscopic examinations before CE. Patients with IDA but no evidence of overt/occult bleeding were separated into three categories based on CE findings: group A - positive; group B - negative/normal; and group C - incomplete/indeterminate. RESULTS: A total of 101 capsules in 97 patients were evaluated. Group A had 25 subjects with positive findings on CE, 18 of whom were managed supportively. Group B consisted of 69 subjects with negative/normal CE, 60 of whom were treated supportively. Group C consisted of three subjects with incomplete CE results. CONCLUSION: In patients with IDA without evidence of gastrointestinal bleeding, CE had a low diagnostic yield (25.7%), which increased to 45.5% after adjusting for low dietary iron intake and menorrhagia. However, CE did not alter management in most patients regardless of findings, and many of the lesions requiring intervention were within reach of standard endoscopes. No predictor of positive results was found. In this patient population, careful history taking and thorough endoscopy could improve CE utilization, although its value is still relatively limited.


Assuntos
Anemia Ferropriva/etiologia , Endoscopia por Cápsula , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
15.
J Can Assoc Gastroenterol ; 4(6): 269-273, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34988365

RESUMO

BACKGROUND: CapsoCam Plus is a capsule endoscopy (CE) system that utilizes four cameras to capture a panoramic view. This has theoretical advantage over conventional forward-viewing CE with limited field of view. Its ease of administration without requiring any additional equipment during the recording also provides a unique opportunity for patients to self-administer the test. We aimed to evaluate real-life experience using this novel system and to determine feasibility of a remote access program. METHODS: Retrospective chart review was conducted for consecutive adult outpatients who underwent CE using CapsoCam Plus. Patients with significant challenges for in-person procedures were selected for remote access through mail courier services. Gastric transit time, small bowel transit time, completion rate, diagnostic yield and adverse events were compared between remote access versus usual practice. RESULTS: Ninety-four patients (52.1% male) were included, with 28 in remote access program. Most common indication was gastrointestinal bleeding (85.1%). Complete examination was achieved in 87 patients. Five (5.3%) patients' capsule remained in stomach during the recording, while two (2.1%) patients missed capsule retrieval. Median small bowel and gastric transit times were 231.9 (interquartile range [IQR] 169.5-308.2) and 27.6 (IQR 13.8-63.5) minutes, respectively. Diagnostic yield was 23.4%. There was no difference in completion rate or transit times between two groups, but diagnostic yield was higher in remote access group (odds ratio 3.80, 95% confidence interval 1.28-11.31). One patient required elective endoscopic retrieval of capsule. CONCLUSION: CapsoCam Plus can be safely administered remotely with a high degree of success, which may facilitate timely investigations while limiting nonessential physical interactions during pandemic.

18.
Arterioscler Thromb Vasc Biol ; 28(10): 1731-7, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18599800

RESUMO

OBJECTIVE: The purpose of this study was to evaluate the effects of whole body overexpression of human ABCG1 on atherosclerosis in apoE(-/-) mice. METHODS AND RESULTS: We generated BAC transgenic mice in which human ABCG1 is expressed from endogenous regulatory signals, leading to a 3- to 7-fold increase in ABCG1 protein across various tissues. Although the ABCG1 BAC transgene rescued lung lipid accumulation in ABCG1(-/-) mice, it did not affect plasma lipid levels, macrophage cholesterol efflux to HDL, atherosclerotic lesion area in apoE(-/-) mice, or levels of tissue cholesterol, cholesterol ester, phospholipids, or triglycerides. Subtle changes in sterol biosynthetic intermediate levels were observed in liver, with chow-fed ABCG1 BAC Tg mice showing a nonsignificant trend toward decreased levels of lathosterol, lanosterol, and desmosterol, and fat-fed mice exhibiting significantly elevated levels of each intermediate. These changes were insufficient to alter ABCA1 expression in liver. CONCLUSIONS: Transgenic human ABCG1 does not influence atherosclerosis in apoE(-/-) mice but may participate in the regulation of tissue cholesterol biosynthesis.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Apolipoproteínas E/metabolismo , Aterosclerose/metabolismo , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Animais , Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Aterosclerose/etiologia , Aterosclerose/patologia , Colesterol/metabolismo , Desmosterol/metabolismo , Gorduras na Dieta , Modelos Animais de Doenças , Homeostase , Humanos , Lipoproteínas/deficiência , Lipoproteínas/genética , Fígado/metabolismo , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Regulação para Cima
19.
Gastrointest Endosc Clin N Am ; 29(3): 471-485, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31078248

RESUMO

Capsule endoscopy (CE) provides visualization of small bowel mucosa for evidence of inflammation. Given its ability to detect subtle mucosal changes, CE is recommended in the diagnostic work-up of small bowel Crohn disease (CD) and also in monitoring mucosal response to therapy in nonstricturing CD. Patency capsule and cross-sectional imaging can reduce risk of capsule retention in patients with suspected stenotic disease. CE is complementary to magnetic resonance enterography, which can provide extraintestinal information. Device-assisted enteroscopy has limited role in CD.


Assuntos
Enteroscopia de Balão/métodos , Endoscopia por Cápsula/métodos , Doença de Crohn/diagnóstico por imagem , Intestino Delgado/diagnóstico por imagem , Radiologistas/psicologia , Humanos , Mucosa Intestinal/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Papel do Médico
20.
Cureus ; 11(6): e4816, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31404354

RESUMO

Background Research suggests that symptoms of post-traumatic stress disorder (PTSD) may be common in physicians who have experienced a traumatic event, but it is unclear if medical residents suffer from similar symptoms. Objective To determine the prevalence of PTSD symptoms in the resident physician population of the University of British Columbia based on the new Diagnostic and Statistical Manual of Mental Disorders-fifth edition (DSM-5) criteria. Method A link to an online questionnaire containing 27 questions, including residency training and year, as well as the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders-fifth edition (PCL-5) was e-mailed and completed by the resident physicians of the University of British Columbia. Results Forty-three residents completed the survey and 38 had complete data. Mean PCL-5 score was 10.3 for the 38 subjects. Differences between PCL-5 score and resident year yielded the following: postgraduate year (PGY)-1=8.6; PGY-2=16.5; PGY-3=3.6; PGY-4=4.0; PGY-5=7.7. With respect to the type of traumatic event and PCL-5 score, the following was observed: Death=5.3, Violence=13.8, Medical Error=8.0, Bullying=38.0, None=45.0. The Kruskal-Wallis test showed no statistically significant differences in total PCL-5 score for PGY or type of traumatic event. Regardless of post-graduate year or trauma experience, four subjects out of 38 (10.5%) had a total PCL-5 score of 33 or greater, while one subject (2.5%) had a score greater than 50. Conclusion The results from this study conclude that resident physicians do suffer from PTSD symptoms at a rate higher than the average American population. As PTSD symptoms can often be very distressing and potentially affect work ethic negatively, further studies are indicated to better understand these symptoms and hopefully lead to better care in treating PTSD symptoms in resident physicians.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA