RESUMO
BACKGROUND: Pseudoaneurysms of the extracranial arterial system are rare. We report a case of a facial artery pseudoaneurysm initially mistaken for an abscess. With bedside ultrasound performed in the Emergency Department (ED) by the treating physician, the mass was identified as a pseudoaneurysm. OBJECTIVES: In this report we review the anatomy of the extracranial arterial system of the head and neck, discuss the pathogenesis and clinical presentation of pseudoaneuryms, and present diagnostic imaging and treatment options for pseudoaneurysms of the face. CASE REPORT: A 51-year-old man presented with facial swelling and pain at the site of a laceration that he had sustained 1 month previously. Before incision and drainage, bedside ultrasound was performed in the ED by the treating physician to confirm the presumptive diagnosis of abscess with possible foreign body. The ultrasound revealed the mass to be a pseudoaneurysm. CONCLUSIONS: Although pseudoaneurysms of the head and neck are rare, a history of trauma should prompt the consideration of a vascular injury with the need for imaging before drainage procedures of a presumed abscess. To our knowledge, the use of clinician-performed bedside ultrasound to detect facial artery pseudoaneurysms has never been reported.
Assuntos
Falso Aneurisma/diagnóstico por imagem , Artérias/diagnóstico por imagem , Bochecha/irrigação sanguínea , Bochecha/diagnóstico por imagem , Artérias/lesões , Humanos , Masculino , Pessoa de Meia-Idade , UltrassonografiaRESUMO
Herein we report investigations into the p38alpha MAP kinase activity of trisubstituted imidazoles that led to the identification of compounds possessing highly potent in vivo activity. The SAR of a novel series of imidazopyridines is demonstrated as well, resulting in compounds possessing cellular potency and enhanced in vivo activity in the rat collagen-induced arthritis model of chronic inflammation.
Assuntos
Anti-Inflamatórios/farmacologia , Imidazóis/farmacologia , Proteína Quinase 14 Ativada por Mitógeno/antagonistas & inibidores , Piridinas/farmacologia , Trifosfato de Adenosina/análogos & derivados , Trifosfato de Adenosina/metabolismo , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacocinética , Benzimidazóis/química , Benzimidazóis/farmacocinética , Benzimidazóis/farmacologia , Edema/tratamento farmacológico , Receptores ErbB/metabolismo , Humanos , Imidazóis/química , Imidazóis/farmacocinética , Camundongos , Camundongos Endogâmicos BALB C , Fragmentos de Peptídeos/metabolismo , Piridinas/química , Piridinas/farmacocinética , Ratos , Relação Estrutura-Atividade , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismoRESUMO
We report the design and discovery of a 2-aminobenzimidazole-based series of potent and highly selective p38alphainhibitors. The lead compound 1 had low-nanomolar activity in both ATP competitive enzyme binding and inhibition of TNFalpha release in macrophages. Compound 18 showed excellent pharmacokinetics properties and oral activity in the rat collagen induced arthritis model compared with other p38 reference compounds. A SAR strategy to address CyP3A4 liability is also described.
Assuntos
Anti-Inflamatórios/síntese química , Benzimidazóis/síntese química , Proteína Quinase 14 Ativada por Mitógeno/antagonistas & inibidores , Administração Oral , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Artrite Experimental/tratamento farmacológico , Benzimidazóis/química , Benzimidazóis/farmacologia , Sítios de Ligação , Disponibilidade Biológica , Colágeno , Cristalografia por Raios X , Desenho de Fármacos , Humanos , Lipopolissacarídeos/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Proteína Quinase 14 Ativada por Mitógeno/química , Modelos Moleculares , Ratos , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
The follow-up of patients with rectal cancer after potentially curative resection has significant financial and clinical implications for patients and society. The ideal regimen for monitoring patients is unknown. We evaluated the self-reported practice patterns of a large, diverse group of experts. There is little information available describing the actual practice of clinicians who perform potentially curative surgery on rectal cancer patients and follow them after recovery. The 1795 members of the American Society of Colon and Rectal Surgeons were asked, via a detailed questionnaire, how often they request 14 discrete follow-up modalities in their patients treated for cure with TNM stage I, II, or III rectal cancer over the first five post-treatment years. 566/1782 (32%) responded and 347 of the respondents (61%) provided evaluable data. Members of the American Society of Colon and Rectal Surgeons typically follow their own patients postoperatively rather than sending them back to their referral source. Office visit and serum CEA level are the most frequently requested items for each of the first five postoperative years. Endoscopy and imaging tests are also used regularly. Considerable variation exists among these highly experienced, highly credentialed experts. The surveillance strategies reported here rely most heavily on relatively simple and inexpensive tests. Endoscopy is employed frequently; imaging tests are employed less often. The observed variation in the intensity of postoperative monitoring is of concern.
Assuntos
Monitorização Fisiológica/métodos , Cuidados Pós-Operatórios/métodos , Neoplasias Retais/cirurgia , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cuidados Pós-Operatórios/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Neoplasias Retais/patologia , Inquéritos e QuestionáriosRESUMO
Human PRL-1, PRL-2, and PRL-3 tyrosine phosphatases induce the malignant transformation of epithelial cells. We tested the hypothesis that the oncogenic effects of PRL occur by increasing cellular proliferation. Cells stably transfected with PRL-1 or PRL-2 exhibited 2.7-3.3-fold increases over control cells in the rate of DNA synthesis and the proportion of cells in S-phase, and they progressed more rapidly from G1 into S. In addition, cells overexpressing either PRL-1 or PRL-2 exhibited enhanced cyclin-dependent kinase 2 (CDK2) activity and significantly lower p21(Cip1/Waf1) protein levels, and PRL-1 overexpressing cells had higher cyclin A protein levels than control cells. We conclude that PRL phosphatases increase cell proliferation by stimulating progression from G1 into S phase, and this process may be dependent on the down regulation of the cyclin dependent kinase inhibitor p21(Cip1/Waf1).
Assuntos
Ciclo Celular/fisiologia , Ciclinas/fisiologia , Proteínas Tirosina Fosfatases/fisiologia , Animais , Apoptose/fisiologia , Quinases relacionadas a CDC2 e CDC28/fisiologia , Divisão Celular/fisiologia , Células Cultivadas , Cricetinae , Ciclina A/fisiologia , Quinase 2 Dependente de Ciclina , Inibidor de Quinase Dependente de Ciclina p21 , Regulação para Baixo , Humanos , Immunoblotting , Reação em Cadeia da Polimerase , Testes de Precipitina , TransfecçãoRESUMO
OBJECTIVES: Inferior vena cava ultrasound (IVC-US) is a noninvasive bedside tool to assess intravascular volume status. This study set out to investigate the interrater reliability of IVC-US by bedside clinician sonographers and determine whether alternative methods of IVC-US such as B-mode and visual estimation are equally reliable to traditional M-mode. METHODS: A convenience sample of adult emergency department (ED) patients was prospectively enrolled. Each patient underwent IVC-US by two different emergency physicians (EPs), each of whom first performed visual estimation of IVC percent collapse and of volume status, followed by caliper measurements in M-mode and B-mode. EPs were blinded to patient data and to the other sonographer's results. For each technique, interrater reliability was determined between the two EPs' assessments using intraclass correlation coefficients (ICC) for continuous data and Cohen's weighted kappa for categorical data. In addition, analysis was performed on M-mode diameter measurements to determine the relationship between sonographer and patient characteristics on interrater reliability. RESULTS: Five EPs performed 92 US exams on 46 patients. Using M-mode, the ICC for maximum IVC diameter was 0.81 (95% confidence interval [CI]=0.67 to 0.89), and for minimum diameter was 0.77 (95% CI=0.62 to 0.87). There were no statistically significant differences between the caliper methods used for IVC measurements (M-mode diameter, B-mode diameter, or B-mode area). Agreement for visually estimated IVC collapse (0.60, 95% CI=0.36 to 0.76) was similar to agreement for calculated M-mode IVC collapse index (0.52, 95% CI=0.27 to 0.71). Cohen's weighted kappa for volume status based on visual estimation of IVC filling (size, shape, and collapse) was 0.64 (95% CI=0.53 to 0.73). ICC values for M-mode diameter measurements were significantly higher in studies involving patients who were noneuvolemic and studies in which sonographers had each performed at least five prior IVC-US. CONCLUSIONS: Emergency physicians' US measurements of IVC diameter have a high degree of interrater reliability. IVC percent collapse by visual estimation or based on caliper measurements have lower, but still moderate to good reliability. The use of the visual estimation technique should be considered by clinicians who have learned to obtain measured parameters of IVC filling because it is equally reliable to traditional M-mode and can be performed more rapidly.
Assuntos
Serviço Hospitalar de Emergência , Sistemas Automatizados de Assistência Junto ao Leito , Veia Cava Inferior/diagnóstico por imagem , Adulto , Humanos , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Prospectivos , Reprodutibilidade dos Testes , Ultrassonografia/métodosRESUMO
BACKGROUND: Testing for troponin has important clinical value for patients who present with typical symptoms of acute coronary syndromes (ACS) such as chest pain (CP). Much less is known about the value of troponin testing for patients who present with other symptoms of ACS (anginal equivalent symptoms). METHODS: The utilization and prognostic value of cardiac troponin I (cTnI) were evaluated at a Veterans Affairs Acute Care Facility. Clinical charts of 1184 predominantly male patients, who submitted specimens for initial cTnI testing by AxSYM, were evaluated for demographic data, cardiovascular risk factors, major diseases, and complaints at the time of testing. The endpoint was defined as all-cause death during a 200-day period after initial testing. RESULTS: Sixty-one percent of cTnI tests were ordered for patients who did not present with CP. Patients presenting with symptoms other than CP did not have significantly lower plasma cTnI than patients with CP. However, patients with symptoms other than CP were rarely diagnosed with ACS unless cTnI was >/=2 microg/L. The mortality during the follow-up period was severalfold higher among patients presenting with symptoms other than CP (CP, 6%; without CP, 22%; P <0.0001, chi(2) test). cTnI >/=0.2 microg/L provided significant additional predictive information for patients who presented with anginal equivalent symptoms such as shortness of breath or general weakness. CONCLUSION: Patients with anginal equivalent symptoms of ACS and low-positive cTnI are less often diagnosed with ACS and have a higher mortality than patients with CP.